Asian Pacific Journal of Cancer Prevention

Shah, Krupa;Parikh, Sonia;Rawal, Rakesh 3025

https://doi.org/10.14456/apjcp.2016.49/APJCP.2016.17.7.3025 KSCI

Chronic myeloid leukaemia (CML) is a clonal myeloproliferative hematopoietic stem cell disorder. Deregulated BCR-ABL fusion tyrosine kinase activity is the main cause of CML disease pathogenesis, making BCR-ABL an ideal target for inhibition. Current tyrosine kinase inhibitors (TKIs) designed to inhibit BCR-ABL oncoprotein activity, have completely transformed the prognosis of CML. Interruption of TKI treatment leads to minimal residual disease reside (MRD), thought to reside in TKI-insensitive leukaemia stem cells which remain a potential reservoir for disease relapse. This highlights the need to develop new therapeutic strategies for CML either as small molecule master TKIs or phytopharmaceuticals derived from nature to achieve chronic molecular remission. This review outlines the past, present and future therapeutic approaches for CML including coverage of relevant mechanisms, whether ABL dependent or independent, and epigenetic factors responsible for developing resistance against TKIs. Appearance of mutant clones along the course of therapy either pre-existing or induced due to therapy is still a challenge for the clinician. A proposed in-vitro model of generating colony forming units from CML stem cells derived from diagnostic samples seems to be achievable in the era of high throughput technology which can take care of single cell genomic profiling.

Basra, Muhammad Asim R;Saher, Manzoor;Athar, Muhammad Makshoof;Raza, Muhammad Hashim 3035

https://doi.org/10.14456/apjcp.2016.50/APJCP.2016.17.7.3035 KSCI

Breast cancer (BC) is the most common malignancy of women worldwide. In the past it was considered as disease of older middle aged women, but the incidence of BC in young females is growing in recent years concordant with studies in Pakistan. In this paper, we reviewed the mutant functions of tumor suppressor genes (BRCA1, BRCA2, p53, ATM and PTEN), epigenetic transformation and involvement of estrogen receptors in development of breast cancer. We further reviewed the current situation of BC in Pakistan that depicts a higher incidence in young females. According to SKMCH and RC data, age group 45-49 years is more prone to BC with high rate of incidence 45.42%. A few studies explored the high expression of ER, PR and HER-2/neu in Pakistani females. Moreover, presence of BRCA1 (c.1961dupA) mutation in Pakistani shows concordance with data in different areas of world. But we are unable to find an authentic study that can explore epigenetic based transformation of breast tumors in Pakistan. This area of research needs more attention to explore the complete picture of BC in Pakistan.

Chaudhary, Ajay K;Chaudhary, Shruti;Ghosh, Kanjaksha;Nadkarni, A 3043

https://doi.org/10.14456/apjcp.2016.51/APJCP.2016.17.7.3043 KSCI

Controlled remodeling of the extracellular matrix (ECM) is essential for cell growth, invasion and metastasis. Matrix metalloproteinases (MMPs) are a family of secreted, zinc-dependent endopeptidases capable of degradation of ECM components. The expression and activity of MMPs in a variety of human cancers have been intensively studied. They play important roles at different steps of malignant tumor formation and have central significance in embryogenesis, tissue remodeling, inflammation, angiogenesis and metastasis. However, increasing evidence demonstrates that MMPs are involved earlier in tumorigenesis. Recent studies also suggest that MMPs play complex roles in tumor progression. MMPs and membrane type (MT)-MMPs are potentially significant therapeutic targets in many cancers, so that designing of specific MMP inhibitors would be helpful for clinical trials. Here, we review the pleiotropic roles of the MMP system in hematological malignancies in-vitro and in-vivo models.

Majeed, Wafa;Iftikhar, Asra;Khaliq, Tanweer;Aslam, Bilal;Muzaffar, Humaira;Atta, Komal;Mahmood, Aisha;Waris, Shahid 3053

https://doi.org/10.14456/apjcp.2016.52/APJCP.2016.17.7.3053 KSCI

Gastric cancer is generally associated with poor survival rates and accounts for a remarkable proportion of global cancer mortality. The prevalence of gastric carcinoma varies in different regions of world and across teh various ethnic groups. On the basis of pathological assessment, gastric cancer can be categorized as intestinal and diffuse carcinomas. The etiology is diverse, including chemical carcinogen exposure, and high salt intake Helicobacter pylori also plays a vital role in the pathogenesis of certain gastric carcinomas. The development of gastric cancer involves various alterations in mRNAs, genes (GOLPH3, MTA2) and proteins (Coronins). miRNAs, Hsa-mir-135b, MiR-21, miR-106b, miR-17, miR-18a, MiR-21, miR-106b, miR-17, miR-18a and MiRNA-375, miRNA-195-5p are the latest diagnostic biomarkers which can facilitate the early diagnosis of gastric carcinomas. Recent development in the treatment strategies for gastric carcinoma include the introduction of monoclonal antibodies, TKI inhibitors, inhibitors of PDGFR ${\beta}$, VEGFR-1, VEGFR-2, Anti-EGFR and anti-HER2 agents which can be applied along with conventional therapies.

Tuorkey, Muobarak J 3061

https://doi.org/10.14456/apjcp.2016.53/APJCP.2016.17.7.3061 KSCI

Exploiting the immune system to abolish cancer growth via vaccination is a promising strategy but that is limited by many clinical issues. For DNA vaccines, viral vectors as a delivery system mediate a strong immune response due to their protein structure, which could afflect the cellular uptake of the genetic vector or even induce cytotoxic immune responses against transfected cells. Recently, synthetic DNA delivery systems have been developed and recommended as much easier and simple approaches for DNA delivery compared with viral vectors. These are based on the attraction of the positively charged cationic transfection reagents to negatively charged DNA molecules, which augments the cellular DNA uptake. In fact, there are three major cellular barriers which hinder successful DNA delivery systems: low uptake across the plasma membrane; inadequate release of DNA molecules with limited stability; and lack of nuclear targeting. Recently, a polysaccharide polymer produced by microalgae has been synthesized in a form of polymeric fiber material poly-N-acetyl glucosamine (p-GlcNAc). Due its unique properties, the F2 gel matrix was suggested as an effective delivery system for immune and gene vaccinations.

Suhda, Saihas;Paramita, Dewi Kartikawati;Fachiroh, Jajah 3065

https://doi.org/10.14456/apjcp.2016.54/APJCP.2016.17.7.3065 KSCI

Single nucleotide polymorphism (SNP) detection has been used extensively for genetic association studies of diseases including cancer. For mass, yet accurate and more economic SNP detection we have optimized tetra primer amplification refractory mutation system polymerase chain reaction (ARMS PCR) to detect three SNPs in the cytochrome P450 2E1 (CYP2E1) gene locus; i.e. rs3813865, rs2070672 and rs3813867. The optimization system strategies used were (1) designing inner and outer primers; (2) determining of their optimum primer concentration ratios; and (3) determining of the optimum PCR annealing temperature. The tetra primer ARMS PCR result could be directly observed using agarose gel electrophoresis. The method succesfully determined three SNPs in CYP2E1 locus, the results being consistent with validation using DNA sequencing and restriction fragment length polymorphisms (RFLP).

Lee, Jeong-Hee;Jin, Hana;Lee, Won Sup;Nagappan, Arulkumar;Choi, Yung Hyun;Kim, GonSup;Jung, Jin-Myung;Ryu, Chung Ho;Shin, Sung Chul;Hong, SoonChan;Kim, Hye Jung 3071

https://doi.org/10.14456/apjcp.2016.55/APJCP.2016.17.7.3071 KSCI

Morin, a flavonoid found in figs and other Moraceae species, displays a variety of biological actions, exerting anti-oxidant, anti-inflammatory and anti-carcinogenic effects. Here, we investigated the anti-cancer activity of morin focusing on anti-adhesive influence. We performed experiments with MDA-MB-231 human breast cancer cells. Morin inhibited TNF-induced cancer cell adhesion to human umbilical vein endothelial cells (HUVECs) without showing any toxicity. It further inhibited the expression of VCAM-1 on MDA-MB-231 cells as well as HUVECs. Morin also decreased the expression of N-cadherin on MDA-MB-231 cells. In addition, there was apparent anti-metastatic activity in vivo. In conclusion, this study suggested that morin inhibits cancer cell adhesion to HUVECs by reducing VCAM-1, and EMT by targeting N-cadherin, and that it features anti-metastatic activity in vivo. Further investigation of possible anti-metastatic activity of morin against human breast cancer cells is warranted.

Murakami, Shinki;Eikawa, Shingo;Kaya, Savas;Imao, Mitsuko;Aji, Toshiki 3077

https://doi.org/10.14456/apjcp.2016.56/APJCP.2016.17.7.3077 KSCI

Various beneficial effects have been described for fermented papaya preparation (FPP: SAIDO-PS501) based on its anti-oxidative and anti-inflammatory functions. The present study was designed to determine the effects of FPP on carcinogenesis in vivo, and immunomodulatory function in vitro. Mice were injected with RL male 1 cells subcutaneously or 3-methylcholantherene (MCA) intravenously to induce cancer and orally or intraperitoneally treated with FPP solution. Human peripheral blood mononuclear cells (PBMC) were obtained from healthy volunteers and patients with atopic dermatitis, treated with FPP, and subjected to measurement of cytokine production and changes in Foxp3-expressing regulatory T cell (Treg) stimulated with phytohemagglutinin (PHA). Administration of FPP suppressed tumor size and the incidence of malignancy. In vitro, treatment of PBMC with FPP induced IL-$1{\beta}$, $TNF{\alpha}$ and $IFN{\gamma}$ production. Moreover, FPP suppressed proliferation of PHA-stimulated Foxp3-expressing Treg. These results suggest that FPP has chemotherapeutic properties.

Amirifard, Nasrin;Sadeghi, Edris;Farshchian, Negin;Haghparast, Abbas;Choubsaz, Mansour 3085

https://doi.org/10.14456/apjcp.2016.57/APJCP.2016.17.7.3085 KSCI

Background: Worldwide, colorectal cancer (CRC) is reported to be the fourth most common cancer in men and the third most common in women. KRAS is a proto-oncogene located on the short arm of chromosome 12. The aim of this study was to evaluate the KRAS oncogene and its relationship it with clinicopathologic features in 33 Kurdish patients. Materials and Methods: Metastatic CRC between 2012 and 2016 that came to Imam Reza hospital, Kermanshah province, Iran, were analysed for KRAS mutations using allele specific PCR primers and pyrosequencing. Correlations between variables was analyzed in PASW SPSS and overall survival curves were plotted in Graph Pad prism 5. Results: The mean age for them at diagnosis was $51.5{\pm}12.6$ years (range, 22-76 years). Among the 33 patients that were sequenced, 12 samples in the KRAS gene had a nucleotide change, 11 in codon 12 and 1 in codon 13.There was no significant relationship between the mutation and clinical and pathological aspects of the disease. Conclusions: Knowledge of the KRAS status can help in decision-making to treat metastatic colorectal cancer patients more efficiently and increase survival. However, many Kurdish people due to economic problems are not able to do this valuable genetic test. In addition, we need more careful research of KRAS oncogene at the molecular level in young populations with more patients.

Dahiya, Neha;Acharya, Anita S;Bachani, Damodar;Sharma, DN;Gupta, Subhash;Haresh, KP;Rath, GK 3095

https://doi.org/10.14456/apjcp.2016.59/APJCP.2016.17.7.3095 KSCI

Background: Cervical cancer is the most frequently diagnosed cancer among women in India. Understanding quality of life (QOL) in women undergoing chemo-radiotherapy for cervical cancer will help in introducing interventions for better care and outcomes in these women. This study assessed QOL before and after chemo-radiotherapy in cervical cancer patients. Materials and Methods: This follow-up study covered sixty-seven newly diagnosed women with advanced cervical cancer (stages 2b to 4b). Structured questionnaires (the European Organization for Research and Treatment of Cancer, EORTC QLQ-C30 and EORTC QLQ-CX24) were used to assess the change in QOL after 6 months of treatment. Results: The mean age of women at the time of detection of cervical cancer was $52.3{\pm}11.29$ years (Range 30-75 years). Six months survival was 92.53%. The mean global health score of cervical cancer patients after six months of treatment was 59.52, which was significantly higher than the pre-treatment score of 50.15 (p=0.00007). Physical, cognitive and emotional functioning improved significantly (p<0.05) after treatment. Fatigue, pain, insomnia and appetite loss improved but episodes of diarrhea increased after treatment. The mean "symptoms score" using EORTC QLQ-CX24 post treatment was 20.0 which was significantly lower as compared to the pre- treatment score 30.0 (p<0.00001). Sexual enjoyment and sexual functioning decreased significantly after treatment. Conclusions: QOL of newly diagnosed cervical cancer patients improved significantly following chemo-radio therapy. Enhancement was also demonstrated on three of the five functional scales of EORTC QLQ-C30. To further improve QOL, interventions focusing on social and psychological support and physical rehabilitation may be needed.

Hav, Monirath;Eav, Sokha;Heang, Nicole;Pich, Pintuna;Lim, Davy;Leang, Vitou;Korn, Aun;Lay, Sanine;Pluot, Michel;Kruy, Leangsim 3101

https://doi.org/10.14456/apjcp.2016.60/APJCP.2016.17.7.3101 KSCI

Background: According to the most recent estimation of GLOBOCAN, Cambodia has the highest incidence and mortality rate of cervical cancer in Southeast Asia. A screen-and-treat strategy using visual inspection with acetic acid (VIA test) and cryotherapy has been implemented in Cambodia's national cervical cancer screening program since 2013. However, where resources are available, cervical cytology with or without high-risk HPV DNA testing is the preferred screening method used in this country. Aim: This study aims to calculate the prevalence of abnormal cervical cytology and explain the possible factors contributing to a reduced quality of cervical cytology among women participating in a hospital-based cervical cancer screening program in Cambodia. Materials and Methods: A descriptive study was conducted using information from the cytology and pathology database in the Department of Pathology of Calmette Hospital between January 2012 and December 2015. Prevalence of abnormal cervical cytology, based on the Bethesda 2001 classification, was calculated. Data on the adequacy of cytological specimens were analyzed in order to explain the factors contributing to a reduced quality of cervical cytology interpretation. Results: Among 6,207 women who participated in the cervical cancer screening program at Calmette Hospital during 2012 and 2015, 388 (6.25%) had abnormal cytology, which could be classified into Atypical Squamous Cells of Undetermined Significance (92 cases; 1.48%), Atypical Squamous Cells - Cannot Exclude High-Grade Intraepithelial Lesion (13 cases; 0.21%), Atypical Glandular Cells (11 cases; 0.18%), Low-Grade Squamous Intraepithelial Lesion (221 cases; 3.56%), High-Grade Squamous Intraepithelial Lesion (26 cases; 0.42%), and Squamous Cell Carcinoma (25 cases; 0.40%). Unsatisfactory smears made up 12.2% of the total cases. The most frequently identified factor leading to unsatisfactory smears was the absence of cells from the transformation zone. Conclusions: The present study showed an overall prevalence of abnormal cervical cytology of 6.25%, which is comparable to that in many large population-based studies in the Asia Pacific region. Nevertheless, the remarkably high rate of unsatisfactory smears in this study justifies further improvement in specimen sampling among Cambodian gynecologists.

Ghahramanian, Akram;Markani, Abdollah Khorrami;Davoodi, Arefeh;Bahrami, Ahad 3105

https://doi.org/10.14456/apjcp.2016.61/APJCP.2016.17.7.3105 KSCI

Background: Patients' spiritual needs increase drastically after a diagnosis of cancer because of its threatening nature. It is very important to recognize any spiritual crisis. This study aimed to determine needs among Iranian patients with cancer. Materials and Methods: This cross-sectional study was undertaken among 200 patients with cancer referred to Alinasab and Shahid Ghazi Tabatabaie hospitals of Tabriz, Iran. The Spiritual Needs Scale was used for data collection. Results: The mean age of participants was $45.9{\pm}16.4$ years. The majority expressed their main spiritual wishes as "think to God", "trust to God", "see others happy", "try for life beside the disease", "to be prayed for by others', and "need for kindness and help others". Regarding the relationship between demographic characteristics, factors related to disease and the total score of spiritual needs, the results of chi-square tests showed a significant statistical correlations with occupation (p=0.01) and number of children (p=0.03). Also the results of Pearson correlation showed that there is a significant statistical correlation between hospitalization frequency and patients' spiritual needs (p<0.01, r=-0.24). Conclusions: Determination of spiritual needs of patients with cancer in this study can help health carers and especially nurses to design appropriate spiritual care programs based on individual preferences.

Ghaem, Haleh;Amiri, Zahra;Kianpour, Fatemeh;Rezaianzadeh, Abbas;Hosseini, Seyed Vahid;Khazraei, Hajar 3111

https://doi.org/10.14456/apjcp.2016.62/APJCP.2016.17.7.3111 KSCI

Background: The goal of this study was to compare the rate of recurrence and occurrence of complications in colorectal cancer patients after two kinds of laparoscopy and laparotomy. Materials and Methods: A follow-up study was carried out among 358 patients who suffered from colorectal cancer from 2012-2014. The data were gathered from colorectal research center in Shiraz, Shahid Faghihi hospital, and analyzed using the chi-square test, logistic regression, and multinomial regression. Results: The average age of these patients was $56.3{\pm}14.6$, 55.0% being men. Moreover, 57.8% of them underwent laparoscopy surgery and 42.2% of the patients underwent laparotomysurgery and the conversion rate was 58.0% which ultimately was put under the category of laparotomy surgery. After biennial median follow-up, differences in the occurrence of complications such as bleeding (hemorrhage), fever, intestine blockage and wound infection in these two kinds of surgery werestatistically significant (P<0.05). However, the rate of recurrence and the patients' ultimate status (alive without disease, alive with disease, and death) did not significantly differ between these two surgery groups. Conclusions: Post-operation complications were laparoscopy surgery were less than those in laparotomy. However, the outcomes such as patients' ultimate status and recurrence were similar between the two groups.

Qureshi, Muhammad Asif;Khan, Saeed;Ujjan, Ikram Din;Iqbal, Asif;Khan, Ramsha;Khan, Bilal Ahmed 3117

https://doi.org/10.14456/apjcp.2016.63/APJCP.2016.17.7.3117 KSCI

Background: Health-care research is a neglected discipline in Pakistan and research related to esophageal cancer (ranks 9th in Pakistani males and 5th in females) is no exception in this regard. Particularly, there are no data available to delineate the overall status of esophageal cancer epidemiological studies in Pakistan. This study describes the first ever effort to make a systematic quantification, in an attempt to provide a road-map to all stakeholders for designing appropriate epidemiological, diagnostic and therapeutic strategies. Materials and Methods: International (PubMed, ISI Web of Knowledge) and local (PakMedinet) scientific databases as well as Google search engine were searched using specified keywords to extract relevant publication. Well-defined inclusion criteria were implemented to select publications for final analyses. All data were recorded by at least 3 authors and consensus data were entered into and analyzed for descriptive statistics (such as frequencies, percentages and annual growth rates) using Microsoft Excel and SPSS software. Results: A total of 79 publications fulfilled the inclusion criteria including 20 publications for which full texts were not available. Of the 79 publications, 59 (74.6%) were original/research publications, 5 (6.3%) were case reports, 4 (5.1%) were research communications, 2 (2.5%) were review articles, 1 was (1.2%) correspondence and 8 (10.1%) were undefined categories. Only 13 (<20%) cities of Pakistan contributed towards the 79 publications. On average, only 1.9 relevant publications/year were published from 1976 (year of first publication) to the present. Alarmingly, a decline in the annual growth at -4.1% was recorded in the last six years. Conclusions: Esophageal cancer research is largely unfathomed in Pakistan. Urgent/dramatic steps are required by all concerned to address this common (and under reported) cancer of Pakistan.

Jeffree, Saffree Mohammad;Mihat, Omar;Lukman, Khamisah Awang;Ibrahim, Mohd Yusof;Kamaludin, Fadzilah;Hassan, Mohd Rohaizat;Kaur, Nirmal;Myint, Than 3123

https://doi.org/10.14456/apjcp.2016.64/APJCP.2016.17.7.3123 KSCI

Background: Cancer is the fourth leading cause of death in Sabah Malaysia with a reported age-standardized incidence rate was 104.9 per 100,000 in 2007. The incidence rate depends on non-mandatory notification in the registry. Under-reporting will provide the false picture of cancer control program effectiveness. The present study was to evaluate the performance of the cancer registry system in terms of representativeness, data quality, simplicity, acceptability and timeliness and provision of recommendations for improvement. Materials and Methods: The evaluation was conducted among key informants in the National Cancer Registry (NCR) and reporting facilities from Feb-May 2012 and was based on US CDC guidelines. Representativeness was assessed by matching cancer case in the Health Information System (HIS) and state pathology records with those in NCR. Data quality was measured through case finding and re-abstracting of medical records by independent auditors. The re-abstracting portion comprised 15 data items. Self-administered questionnaires were used to assess simplicity and acceptability. Timeliness was measured from date of diagnosis to date of notification received and data dissemination. Results: Of 4613 cancer cases reported in HIS, 83.3% were matched with cancer registry. In the state pathology centre, 99.8% was notified to registry. Duplication of notification was 3%. Data completeness calculated for 104 samples was 63.4%. Registrars perceived simplicity in coding diagnosis as moderate. Notification process was moderately acceptable. Median duration of interval 1 was 5.7 months. Conclusions: The performances of registry's attributes are fairly positive in terms of simplicity, case reporting sensitivity, and predictive value positive. It is moderately acceptable, data completeness and inflexible. The usefulness of registry is the area of concern to achieve registry objectives. Timeliness of reporting is within international standard, whereas timeliness to data dissemination was longer up to 4 years. Integration between existing HIS and national registration department will improve data quality.

Zekri, Abdel-Rahman N;Sobhy, Esraa;Hussein, Nehal;Ahmed, Ola S;Hussein, Amira;Shoman, Sahar;Soliman, Amira H;El-Din, Hanaa M Alam 3131

https://doi.org/10.14456/apjcp.2016.65/APJCP.2016.17.7.3131 KSCI

Several studies have addressed the possible role of hepatitis C virus genotype-4 (HCV GT4) in apoptosis. However, this still not fully understood. In the current study a re-constructed clone of E1/E2 polyprotein region of the HCV GT4 was transfected into the Huh7 cell line and a human apoptotic PCR array of 84 genes was used to investigate its possible significance for apoptosis. Out of the 84 genes, only 35 showed significant differential expression, 12 genes being up-regulated and 23 down-regulated. The highest-up regulated genes were APAF1 (apoptotic peptidase-activating factor 1), BID (BH3 interacting domain death agonist) and BCL 10 (B-cell CLL/lymphoma protein 10) with fold regulation of 33.2, 30.1 and 18.9, respectively. The most down-regulated were FAS (TNF receptor super family), TNFRSF10B (tumor necrosis factor receptor super-family member 10b) and FADD (FAS-associated death domain) with fold regulation of -30.2, -27.7 and -14.9, respectively. These results suggest that the E1/E2 proteins may be involved in HCV-induced pathogenesis by modulating apoptosis through the induction of the intrinsic apoptosis pathway and disruption of the BCL2 gene family.

Farghadani, Reyhaneh;Haerian, Batoul Sadat;Ebrahim, Nader Ale;Muniandy, Sekaran 3139

https://doi.org/10.14456/apjcp.2016.66/APJCP.2016.17.7.3139 KSCI

Cancer is the leading cause of morbidity and mortality worldwide, characterized by irregular cell growth. Cytotoxicity or killing tumor cells that divide rapidly is the basic function of chemotherapeutic drugs. However, these agents can damage normal dividing cells, leading to adverse effects in the body. In view of great advances in cancer therapy, which are increasingly reported each year, we quantitatively and qualitatively evaluated the papers published between 1981 and December 2015, with a closer look at the highly cited papers (HCPs), for a better understanding of literature related to cytotoxicity in cancer therapy. Online documents in the Web of Science (WOS) database were analyzed based on the publication year, the number of times they were cited, research area, source, language, document type, countries, organization-enhanced and funding agencies. A total of 3,473 publications relevant to the target key words were found in the WOS database over 35 years and 86% of them (n=2,993) were published between 2000-2015. These papers had been cited 54,330 times without self-citation from 1981 to 2015. Of the 3,473 publications, 17 (3,557citations) were the most frequently cited ones between 2005 and 2015. The topmost HCP was about generating a comprehensive preclinical database (CCLE) with 825 (23.2%) citations. One third of the remaining HCPs had focused on drug discovery through improving conventional therapeutic agents such as metformin and ginseng. Another 33% of the HCPs concerned engineered nanoparticles (NPs) such as polyamidoamine (PAMAM) dendritic polymers, PTX/SPIO-loaded PLGAs and cell-derived NPs to increase drug effectiveness and decrease drug toxicity in cancer therapy. The remaining HCPs reported novel factors such as miR-205, Nrf2 and p27 suggesting their interference with development of cancer in targeted cancer therapy. In conclusion, analysis of 35-year publications and HCPs on cytotoxicity in cancer in the present report provides opportunities for a better understanding the extent of topics published and may help future research in this area.

Tangjitgamol, Siriwan;Kantathavorn, Nuttavut;Kittisiam, Thannaporn;Chaowawanit, Woraphot;Phoolcharoen, Natacha;Manusirivithaya, Sumonmal;Khunnarong, Jakkapan;Srijaipracharoen, Sunamchok;Saeloo, Siriporn;Krongthong, Waraporn;Supawattanabodee, Busaba;Thavaramara, Thaovalai;Pataradool, Kamol 3147

https://doi.org/10.14456/apjcp.2016.67/APJCP.2016.17.7.3147 KSCI

Background: Many strategies are required for cervical cancer reduction e.g. provision of education cautious sexual behavior, HPV vaccination, and early detection of pre-invasive cervical lesions and invasive cancer. Basic health data for cervical cytology/ HPV DNA and associated factors are important to make an appropriate policy to fight against cervical cancer. Aims: To assess the prevalence of abnormal cervical cytology and/or HPV DNA and associated factors, including sexual behavior, among Bangkok Metropolitan women. Materials and Methods: Thai women, aged 25-to-65 years old, had lived in Bangkok for ${\geq}5$ years were invited into the study. Liquid-based cervical cytology and HPV DNA tests were performed. Personal data were collected. Main Outcomes Measures: Rates of abnormal cytology and/ or high-risk HPV (HR-HPV) and factors associated with abnormal test (s) were studied. Results: Abnormal cytology and positive HR-HPV were found in 6.3% (279/4442 women) and 6.7% (295/4428), respectively. The most common abnormal cytology was ASC-US (3.5%) while the most common HR-HPV genotype was HPV 16 (1.4%) followed by HPV 52 (1.0%), HPV 58 (0.9%), and HPV 18 and HPV 51 at equal frequency (0.7%). Both tests were abnormal in 1.6% (71/4428 women). Rates of HR-HPV detection were directly associated with severity of abnormal cytology: 5.4% among normal cytology and 13.0%, 30.8%, 40.0%, 39.5%, 56.3% and 100.0% among ASC-US, ASC-H, AGC-NOS, LSIL, HSIL, and SCC, respectively. Some 5% of women who had no HR-HPV had abnormal cytology, in which 0.3% had ${\geq}$ HSIL. Factors associated with abnormal cytology or HR-HPV were: age ${\leq}40$ years, education lower than (for cytology) or higher than bachelor for HR-HPV), history of sexual intercourse, and sexual partners ${\geq}2$. Conclusions: Rates for abnormal cytology and HR-HPV detection were 6.3% and 6.7% HR-HPV detection was directly associated with severity of abnormal cytology. Significant associated factors were age ${\leq}40$ years, lower education, history of sexual intercourse, and sexual partners ${\geq}2$.

Yeang, Shu Hui;Chan, Alexandre;Tan, Chuen Wen;Lim, Soon Thye;Ng, HengJoo 3155

https://doi.org/10.14456/apjcp.2016.68/APJCP.2016.17.7.3155 KSCI

Background: L-asparaginase (ASNase) is commonly used in the treatment of acute lymphoblastic leukemia (ALL) and natural killer (NK)/T-cell lymphoma. This study was designed to describe the incidence of toxicity associated with ASNase in Asian adults. Secondary objectives were to investigate the management and impact of toxicity on subsequent ASNase use, and to compare the actual management against current recommendations. Materials and Methods: In this retrospective, multi-center, observational study, Asian patients ${\geq}18$ years old who received ${\geq}1$ dose of the native E. coli ASNase from 2008 to 2013 were included. Patients were excluded if they did not receive ASNase. Endpoints of this study were development of specific toxicities, whether ASNase was discontinued or re-challenged, and developmentg of recurrent toxicity. All data analyses were performed using SPSS version 20.0. Results: A total of 56 patients were analyzed. Mean (${\pm}SD$) age was 36.2 (${\pm}15.2$) years old, with 62.5% being males, 55.4% with ALL and 28.6% with NK/T-cell lymphoma. Hypersensitivity (12.5%) was associated with the highest incidence of toxicity (6 out of 7 patients had Grade 3 and 4 toxicity), followed by 10.7% for hepatic transaminitis, 3.6% for non-CNS thrombosis and 1.8% each for hyperbilirubinemia and pancreatitis. Hypersensitivity recurred in the 3 patients who were re-challenged with E. coli ASNase. Conclusions: ASNase is associated with a wide range of toxicities, with hypersensitivity being the most commonly observed among Asian adult patients.

Ezz El Din, M 3161

https://doi.org/10.14456/apjcp.2016.69/APJCP.2016.17.7.3161 KSCI

Background: Metastatic renal cell carcinoma (mRCC) status as poor prognosis improved with the introduction of tyrosine-kinase inhibitors, especially sunitinib. There is sparse data reporting from our region on use of sunitinib in metastatic RCC. Thus the present study explores sunitinib usage at our institute. Materials and Methods: An unselected population of patients with metastatic RCC receiving sunitinib was analyzed with respect to patient characteristics, response, toxicity, and outcomes. Results: Fourty-nine patients with a median age of 50.5 years (range 21-71 years) were included. Most were male (61.2%). Twenty‑one (42.9%) had metastatic disease at presentation. Sunitinib was first line therapy in 45. Conventional clear cell carcinoma was the most common pathology present (39 patients; 79.59 %). The most common site of metastasis was the lung (75.5%). Most patients (30) were started at a dose of 50 mg once a day for 4 weeks and then 2 weeks rest. Clinical benefit rate was 73.5% (n= 36), and 22.5% (n= 11) demonstrated progressive disease at first imaging evaluation within the first 3-6 months. The following objective response performed for patients was 48.9% (n=24) and progression at 24.5 % (n=12). The median follow‑up was 16 months (range, 4-34 months), the overall estimated median PFS was 9 months and the estimated median OS was 15 months. Conclusions: This study demonstrated sunitinib is tolerable and effective in advanced/metastatic RCC Egyptian patients and indicates we should further seek second and third lines to increase survival equivalence as reported in the worldwide literature.

Fabre, Bibiana;Grosman, Halina;Gonzalez, Diego;Machulsky, Nahuel Fernandez;Repetto, Esteban M;Mesch, Viviana;Lopez, Miguel Angel;Mazza, Osvaldo;Berg, Gabriela 3167

https://doi.org/10.14456/apjcp.2016.70/APJCP.2016.17.7.3167 KSCI

Prostate cancer (PCa) is one of the most common diseases in men. It is important to assess prognostic factors and whether high cortisol levels and complex hormonal interactions could be responsible for PCa development. We evaluated the relationship between cortisol, leptin and estrogens in 141 men, 71 with PCa and the remaining 70 constituting a low risk group (LRG). They were recruited for this study from a total of 2906 middle-aged men (ages 45-70 years) who completed an evaluation for prostatic diseases at the Urology Division, Hospital de Clínicas "$Jos{\acute{e}}$ de San $Mart{\acute{i}}n$", University of Buenos Aires, in May 2009. In this cross sectional study, cortisol, PSA, total-testosterone, free-testosterone, bioavailable testosterone, LH and estradiol were measured in serum. We observed increased cortisol levels in PCa patients as compared to LRG cases (p=0.004,). Leptin and estradiol levels were also higher in PCa patients (p=0.048; p<0.0001, respectively). Logistic regression analysis indicated that serum cortisol (OR: 1.110 (95% CI 1.016-1.213), p=0.022), estradiol (OR: 1.044 (95% CI 1.008-1.081), p=0.016) and leptin (OR: 1.248 (95% CI 1.048-1.487), p=0.013) explained 27% of the variance of dependent variables, even after adjusting for age, smoking, BMI and waist circumference. We found increased cortisol levels in PCa patients as compared to LRG, as well as an altered circulating hormonal profile.

Elias, Fadia;Khuri, Fadlo R;Adib, Salim M;Karam, Rita;Harb, Hilda;Awar, May;Zalloua, Pierre;Ammar, Walid 3173

https://doi.org/10.14456/apjcp.2016.71/APJCP.2016.17.7.3173 KSCI

Background: The Ministry of Public Health (MOPH) in Lebanon provides cancer drugs free of charge for uninsured patients who account for more than half the total case-load. Other categories of cancer care are subsidized under more stringent eligibility criteria. MOPH's large database offers an excellent opportunity to analyze the cost of cancer treatment in Lebanon. Materials and Methods: Using utilization and spending data accumulated at MOPH during 2008-2013, the cost to the public budget of cancer drugs was assessed per case and per drug type. Results: The average annual cost of cancer drugs was 6,475$ per patient. Total cancer drug costs were highest for breast cancer, followed by chronic myeloid leukemia (CML), colorectal cancer, lung cancer, and Non-Hodgkin's lymphoma (NHL), which together represented 74% of total MOPH cancer drug expenditure. The annual average cancer drug cost per case was highest for CML ($31,037), followed by NHL ($11,566). Trastuzumab represented 26% and Imatinib 15% of total MOPH cancer drug expenditure over six years. Conclusions: Sustained increase in cancer drug cost threatens the sustainability of MOPH coverage, so crucial for socially vulnerable citizens. To enhance the bargaining position with pharmaceutical firms for drug cost containment in a small market like Lebanon, drug price comparisons with neighboring countries which have already obtained lower prices may succeed in lowering drug costs.

Tze, Christina Ng Van;Fitzgerald, Henry;Qureshi, Akhtar;Tan, Huck Joo;Low, May Lee 3179

https://doi.org/10.14456/apjcp.2016.72/APJCP.2016.17.7.3179 KSCI

The aim of this study was to assess the rate of uptake of a customised annual Colorectal Cancer Awareness, Screening and Treatment Project (CCASTP) using faecal immunohistochemical test (FIT) kits in low income communities in Malaysia. The immediate objectives were (1) to evaluate the level of adherence of CRC screening among low-income groups, (2) to assess the knowledge and awareness of the screened population and (3) to assess the accuracy of FIT kits. A total of 1,581 FIT kits were distributed between years 2010 to 2015 to healthy asymptomatic participants of the annual CCASTP organized by Empowered - the Cancer Advocacy Society of Malaysia. Data for socio-demographic characteristics, critical health and lifestyle information of the registered subjects were collected. Findings for use of the FIT kits were collected when they were returned for stool analyses. Those testingd positive were invited to undergo a colonoscopy examination. A total of 1,436 (90.8%) of the subjects retuned the FIT-kits, showing high compliance. Among the 129 subjects with positive FIT results, 92 (71.3%) underwent colonoscopy. Six cases (6.5%) of CRC were found. Based on the data collected, the level of awareness of stool examination and knowledge about CRC was poor amongst the participants. Gender, age group, ethnicity and risk factors (i.e. smoking, lack of exercise and low consumption of fresh fruits) were associated with positive FIT-kit results. In conclusion, CRC screening can be performed in the community with a single FIT-kit. Although CRC knowledge and awareness is poor in low-income communities, the average return rate of the FIT kits and rate of colonoscopy examination were 91.2% and 70.3%, respectively.

Alikhassi, Afsaneh;Saeed, Farzanefar;Abbasi, Mehrshad;Omranipour, Ramesh;Mahmoodzadeh, Habibollah;Najafi, Massoome;Gity, Masoumeh;Kheradmand, Ali 3185

https://doi.org/10.14456/apjcp.2016.73/APJCP.2016.17.7.3185 KSCI

Background: This study was designed to compare radioguided versus routine wire localization of nonpalpable non-malignant breast lesions in terms of efficacy for complete excision, ease of use, time saving, and cosmetic outcome. Materials and Methods: Patients with non-palpable breast masses and non-malignant core biopsy results who were candidates for complete surgical lumpectomy were enrolled and randomly assigned to radioguided or wire localization groups. Radiologic, surgical, and pathologic data were collected and analyzed to determine the difficulty and duration of each procedure, ease of use, accuracy, and cosmetic outcomes. Results: This prospective randomized study included 60 patients, randomly divided into wire guided localization (WGL) or radioguided occult lesion localization (ROLL) groups. The mean duration of localization under ultrasound guidance was shorter in the ROLL group (14.4 min) than in the WGL group (16.5 min) (p<0.001). The ROLL method was significantly easier for radiologists (p=0.0001). The mean duration of the surgical procedure was 22.6 min (${\pm}10.3min$) for ROLL and 23.6 min (${\pm}9.6min$) for WGL (p=0.6), a non-significant difference. Radiography of the surgical specimens showed 100% lesion excision with clear margins, as proved by pathologic examination, with both techniques. The surgical specimens were slightly heavier in the ROLL group, but the difference was not significant (p=0.06). Conclusions: The ROLL technique provides effective, fast, and simple localization and excision of non-palpable non-malignant breast lesions.

Hussein, Nawfal R;Balatay, Amer A;Assafi, Mahde S;Al-Mufty, Tamara Abdulezel;Khalil, Amira S 3191

https://doi.org/10.14456/apjcp.2016.74/APJCP.2016.17.7.3191 KSCI

Background: The human papilloma virus (HPV) is considered as the major risk factor for the development of cervical cancer. This virus is of different genotypes and generally can be classified into high and low risk types. Objective: To determine the rate of high risk HPV genotypes in women with vaginal discharge and lower abdominal pain in Kurdistan region, Iraq. Materials and Methods: Cervical swabs were taken from 104 women. DNA was extracted and the polymerase chain reaction (PCR) technique was used to determine the presence of high risk genotypes. Results: It was found that 13/104 (12.5%) of the samples were positive for high risk HPV genotypes. Amongst those who were positive, 4/13 (30.7%) were typed as genotype 16 and 7/13 (53.8%) showed mixed genotyping. On the other hand, genotypes 53 and 56 were found in only one sample each. Conclusions: High risk HPV genotypes are not uncommon and further community based study is needed to determine the prevalence of HPV and its genotypes and plan for prevention of infection.

Al-Zou, Amer Bin;Thabit, Mazen Abood Bin;Al-Sakkaf, Khalid Abdulla;Basaleem, Huda Omer 3195

https://doi.org/10.14456/apjcp.2016.75/APJCP.2016.17.7.3195 KSCI

Background: Skin cancer is a group of heterogeneous malignancies, in general classified into non-melanoma skin cancer (NMSC) and melanoma skin cancer (MSC). Incidences are high in many parts in the world with considerable geographical and racial variation. In the Yemen, there has been scarce information about skin cancer. The aim of this study was to evaluate the demographic characteristics and histological trend of skin cancer in Southern Governorates of Yemen. Materials and Methods: This retrospective study covered 204 cases of skin cancer at the Modern Histopathology Laboratory and Aden Cancer Registry and Research Center, Faculty of Medicine and Health Sciences, University of Aden, for the period 2006-2013. Data were classified regarding different demographic and tumor related variables and analyzed using CanReg-4 for cancer registry and SPSS (version 21). Results: The commonest encountered skin cancer was NMSC (93.1%). Generally, skin cancer appears slightly more frequently in females than males with a 1:1.06 male: female ratio, with a mean age of 62.9 years. Slightly higher than one-third (36.3%) were from Aden governorate. The head and neck proved to be the most common site in both males and females (58%). Basal cell carcinoma (BCC) is the most common histological type of skin cancer (50.5%). Conclusions: Skin cancer is a common cancer in patients living in southern governorates of Yemen. The pattern appears nearly similar to the international figures with a low incidence of MSC.

Kanthiya, Kanjana;Khunnarong, Jakkapan;Tangjitgamol, Siriwan;Puripat, Napaporn;Tanvanich, Sujitra 3201

https://doi.org/10.14456/apjcp.2016.76/APJCP.2016.17.7.3201 KSCI

Purpose: To evaluate the expression of p16 and Ki67 in cervical intraepithelial neoplasia (CIN) and cancer. Materials and Methods: We performed a immunohistochemical study of p16 and Ki67 in 243 cervical tissues - 53 non-dysplastic lesions, 106 CIN1, 61 CIN2/3 and 23 squamous cell carcinomas. The expression of p16 and Ki67 was interpreted independently by 2 researchers and the sensitivity and specificity to detect clinically significant lesions (${\geq}CIN2$) were determined. Results: The overall agreement results of positive or negative immunostaining of intra-inter observer variability were 0.659 for p16 and 0.808 for Ki67. p16 expression was demonstrated in 91.3% of invasive carcinomas, 78.7% of CIN2/3, 10.4% of CIN1 and 9.4% of non-dysplasic lesions. The corresponding Ki67 expression was: 100% of all invasive carcinomas, 75.4% of CIN2/3, 22.6% of CIN1, and 11.3% with non-dysplasia. The expression was significantly different between CIN2/3 vs CIN1 for both p16 and Ki67 (p-values <0.001 both), and cancer vs CIN2/3 for Ki67 (p-value 0.008). The differences were not significant between CIN1 vs non-dysplasia (p-values 1.000 for p16 and 0.130 of Ki67), and cancer vs CIN2/3 for p16 (p value 0.219). The sensitivity and specificity to detect > CIN2 were 84.5% and 90.5% by p16 and 82.1% and 88.6% by Ki67. Conclusions: The rates for 16 and Ki67 expression were directly associated with the severity of cervical lesions. Significant differences in these markers expression may be useful in cases with equivocal histologic features among cervical intraepithelial lesions, but not between CIN1 and non-dysplastic lesions. The two markers had high sensitivity and specificity in determining >CIN2.

Lisboa, Isabel Neves Duarte;de Azevedo Macena, Monica Suela;da Conceicao Dias Fernandes, Maria Isabel;de Almeida Medeiros, Ana Beatriz;de Lima, Cyndi Fernandes;de Carvalho Lira, Ana Luisa Brandao 3207

https://doi.org/10.14456/apjcp.2016.77/APJCP.2016.17.7.3207 KSCI

Background: Skin cancer has a remarkable importance given the high incidence in the population. In Brazil, it is estimated that there were 98,420 new cases of non-melanoma skin cancer among men and 83,710 new cases among women in 2014. Objectives: To verify signs and symptoms present in patients with skin neoplasms according to the literature and relate them to the nursing diagnoses of NANDA International. Materials and Methods: Integrative literature review carried out from March to May 2015 in the databases: Cumulative Index to Nursing and Allied Health Literature, SCOPUS, National Library of Medicine and Nattional Institutes of Health, Latin American and Caribbean Sciences of Health and Web of Science. The descriptors used were: 'Signs and Symptoms' and 'Skin Neoplasms'. Sixteen articles were identified as the final sample. After review, the signs and symptoms of skin cancer identified in the literature were related to the defining characteristics present in NANDA International, with the aim to trace possible nursing diagnoses. Results: The most prevalent signs and symptoms were: asymmetric and well circumscribed nodules with irregular borders; speckles with modified color aspect; ulcerations; blisters; pain; itching; and bleeding. The principal nursing diagnoses outlined were: risk for impaired skin integrity; impaired skin integrity; acute pain; risk of shock; and impaired comfort. Conclusions: The identification of signs and symptoms present in patients with skin cancer and the relationships of these with the nursing diagnoses of NANDA International provide a basis for qualified and systematized nursing care to this clientele.

Poomipark, Natwadee;Flatley, Janet E;Hill, Marilyn H;Mangnall, Barbara;Azar, Elnaz;Grabowski, Peter;Powers, Hilary J 3213

https://doi.org/10.14456/apjcp.2016.78/APJCP.2016.17.7.3213 KSCI

Background: Methyl donor status influences DNA stability and DNA methylation although little is known about effects on DNA methyltransferases. The aim of this study was to determine whether methyl-donor status influences DNA methyltransferase (Dnmt) gene expression in cervical cancer cells, and if so, whether there are associated effects on global DNA methylation. Materials and Methods: The human cervical cancer cell line, C4-II, was grown in complete medium and medium depleted of folate (F-M+) and folate and methionine (F-M-). Growth rate, intracellular folate, intracellular methionine and homocysteine in the extracellular medium were measured to validate the cancer cell model of methyl donor depletion. Dnmt expression was measured by qRT-PCR using relative quantification and global DNA methylation was measured using a flow cytometric method. Results: Intracellular folate and methionine concentrations were significantly reduced after growth in depleted media. Growth rate was also reduced in response to methyl donor depletion. Extracellular homocysteine was raised compared with controls, indicating disturbance to the methyl cycle. Combined folate and methionine depletion led to a significant down-regulation of Dnmt3a and Dnmt3b; this was associated with an 18% reduction in global DNA methylation compared with controls. Effects of folate and methionine depletion on Dnmt3a and 3b expression were reversed by transferring depleted cells to complete medium. Conclusions: Methyl donor status can evidently influence expression of Dnmts in cervical cancer cells, which is associated with DNA global hypomethylation. Effects on Dnmt expression are reversible, suggesting reversible modulating effects of dietary methyl donor intake on gene expression, which may be relevant for cancer progression.

Muhammad, Siti Nur Hasyila;Mokhtar, Noor Fatmawati;Yaacob, Nik Soriani 3223

https://doi.org/10.14456/apjcp.2016.79/APJCP.2016.17.7.3223 KSCI

Reports indicate that 15-deoxy-delta-12,14-prostaglandin-J2 (15d-PGJ2) has anticancer activities, but its mechanisms of action have yet to be fully elucidated. We therefore investigated the effects of 15d-PGJ2 on the human breast cancer cell lines, MCF-7 (estrogen receptor $ER{\alpha}+/ER{\beta}+$) and MDA-MB-231 ($ER{\alpha}-/ER{\beta}+$). Cellular proliferation and cytotoxicity were determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays while apoptosis was determined by fluorescence microscopy and flow cytometry using annexin V-propidium iodide (PI) staining. ER expression was determined by Western blotting. Intracellular calcium was stained with Fluo-4 AM while intracellular caspase activities were detected with Caspase-$FLICA(R)$ and measured by flow cytometry. We showed that 15d-PGJ2 caused a significant increase in apoptosis in MCF-7 and MDA-MB-231 cells. $ER{\alpha}$ protein expression was reduced in treated MCF-7 cells but pre-incubation with the $ER{\alpha}$ inhibitor' ICI 182 780' did not affect the percentage of apoptotic cells. The expression of $ER{\beta}$ was unchanged in both cell lines. In addition, 15d-PGJ2 increased intracellular calcium ($Ca^{2+}$) staining and caspase 8, 9 and 3/7 activities. We therefore conclude that 15d-PGJ2 induces caspase-dependent apoptosis that is associated with an influx of intracellular $Ca^{2+}$ with no involvement of ER signaling.

Zain, Norhayati Mohd;Seriramulu, Vengkatha Priya;Chelliah, Kanaga Kumari 3229

https://doi.org/10.14456/apjcp.2016.80/APJCP.2016.17.7.3229 KSCI

Background: Bone mineral density (BMD) is a lifetime marker of estrogen in a woman's body and has been associated with increased breast cancer risk. Nonetheless the actual association is still debatable. Furthermore, estrogen is very crucial in maintaining human bone density and gradually decreases over age. A systematic search was conducted to assess any association of BMD with breast cancer risk factors among premenopausal and postmenopausal women. Materials and Methods: Review identification was performed through databases searching on MEDLINE, CINAHL and SCOPUS and 19 qualified studies were elected. The keywords used were "bone mineral density", "breast cancer", and "breast density". Results: A total of 19 articles showed variation with the majority of the studies focused on postmenopausal and a few focused on premenopausal women. Overall there was no concensus on effects. Conclusions: An enormous effort is being undertaken by researchers to prove that BMD might be one of the significant risk factors for breast cancer.

Susilawati, Dwi;Sitaresmi, Mei;Handayani, Krisna;Ven, Peter van de;Sutaryo, Sutaryo;Kaspers, Gertjan;Mostert, Saskia 3235

https://doi.org/10.14456/apjcp.2016.81/APJCP.2016.17.7.3235 KSCI

Background: Complementary alternative medicine (CAM) use in children with cancer is widespread. Health-care providers (HCP) need to acknowledge and address this need. This study explored and compared perspectives on CAM of HCP and parents of young patients with cancer in Indonesia. Materials and Methods: We conducted a cross-sectional study using semi-structured questionnaires in HCP and parents of childhood cancer patients at an Indonesian academic hospital. Results: A total of 351 respondents participated: 175 HCP (response rate 80%) and 176 parents (response rate 80%). Parents were more likely than HCP to think that chemotherapy can cure cancer (80% compared to 69%, P=0.013). Nearly half of all parents (46%) and HCP (45%) doubted whether CAM can cure cancer. Parents were more likely than HCP to think that CAM can be helpful in childhood cancer treatment (54% compared to 35%, P=0.003). The most recommended CAM by HCP was self-prayer (93%). Reasons for recommending CAM were: hope for improvement of the child's condition (48%), patient wants to stop treatment (42%). Most discouraged CAM by HCP was by old-smart people (70%), the reasons being: lack of evidence for usefulness (77%), lack of CAM knowledge (75%). The proportion thinking that patients were unlikely to raise the CAM topic if they perceived that doctors were skeptical was higher in parents than in HCP (52% versus 1%) (P<0.001). Most HCP (71%) and parents (77%) acknowledged that their knowledge about safety and efficacy of CAM was inadequate (P=ns). The proportion that wanted to learn or read more about CAM was higher among parents than HCP (48% compared to 31%, P=0.002). Conclusions: HCP and parents have different perspectives on CAM use in children with cancer. HCP should enhance their CAM knowledge and encourage open communication about CAM with parents. If doctors' skepticism is perceived, parents are unlikely to raise CAM as a topic.

Moradi, Ghobad;Karimi, Kohsar;Esmailnasab, Nader;Roshani, Daem 3243

https://doi.org/10.14456/apjcp.2016.82/APJCP.2016.17.7.3243 KSCI

Background: Stomach cancer is the fourth most common cancer and the second leading cause of death from cancer in the world. In Iran, this type of cancer has high rates of incidence and mortality. This study aimed to assess the survival rate of patients with stomach cancer and its determinants in Kurdistan, a province with one of the highest incidence rates of stomach cancer in the country. Materials and Methods: We studied a total of 202 patients with stomach cancer who were admitted to Tohid Hospital in Sanandaj from 2009 to 2013. Using Kaplan-Meier nonparametric methods the survival rate of patients was calculated in terms of different levels of age at diagnosis, gender, education, residential area, occupation, underweight, and clinical variables including tumor histology, site of tumor, disease stage, and type of treatment. In addition, we compared the survival rates using the log-rank test. Finally, Cox proportional hazards regression was applied using Stata 12 and R 3.1.0 software. The significance level was set at 0.05. Results: The mean age at diagnosis was $64.7{\pm}12.0$ years. The survival rate of patients with stomach cancer was 43.9% and 7% at the first and the fifth year after diagnosis, respectively. The results of log-rank test showed significant relationships between survival and age at diagnosis, education, disease stage, type of treatment, and degree of being underweight (P<0.05). Moreover, according to the results of Cox proportional hazards regression model, the variables of education, disease stage, and type of treatment were associated with patient survival (P<0.05). Conclusions: The survival rate of patients with stomach cancer is low and the prognosis is very poor. Given the poor prognosis of the patients, it is critical to find ways for early diagnosis and facilitating timely access to effective treatment methods.

Igawa, Satoshi;Sato, Yuichi;Ishihara, Mikiko;Kasajima, Masashi;Kusuhara, Seiichiro;Nakahara, Yoshiro;Otani, Sakiko;Fukui, Tomoya;Katagiri, Masato;Sasaki, Jiichiro;Masuda, Noriyuki 3249

https://doi.org/10.14456/apjcp.2016.83/APJCP.2016.17.7.3249 KSCI

Background: Pemetrexed monotherapy has come to be recognized as one of the standard second-line therapies for advanced non-squamous non-small cell lung cancer (NSCLC). However, there have been no reports of studies that have evaluated the efficacy of pemetrexed according to type of active EGFR mutation, i.e., an exon 19 deletion or an L858R point mutation. Materials and Methods: The records of non-squamous NSCLC patients harboring an EGFR mutation who received pemetrexed monotherapy as a second or later line of chemotherapy at Kitasato University Hospital between March 2010 and October 2015 were retrospectively reviewed, and the treatment outcomes were evaluated. Results: The overall response rate and progression-free survival time (PFS) of the 53 patients with non-squamous NSCLC were 15.1% and 2.3 months, respectively. There were significant differences between the disease control rate (37.5% vs. 76.2%) and PFS time (1.8 months vs. 3.3 months) of the exon 19 deletion group and the L858R point mutation group, and a multivariate analysis identified type of EGFR mutation as well as performance status (PS) as independent predictors of PFS. Conclusions: The clinical data obtained in this study provided a valuable rationale for considering type of EGFR mutation as well as non-squamous histology as predictors of the efficacy of pemetrexed monotherapy.

Tabassum, Ifrah;Mahmood, Humera;Faheem, Mohammad 3255

https://doi.org/10.14456/apjcp.2016.84/APJCP.2016.17.7.3255 KSCI

Background: There has been much research work in the past to ascertain the association between type 2 diabetes mellitus and breast cancer, but definitive evidence has been scanty. The present study was carried out to determine the association of type 2 diabetes mellitus with breast cancer in the female population of Northern Pakistan. Materials and Methods: This case-control study was carried out in the Oncology Department of NORI Hospital. A total of 400 patients were included. Data were entered into PSPP 0.8.1. Two-tailed significance tests were used and a p-value of 0.05 was considered significant. Results: There were a higher percentage of postmenopausal women in the diabetic breast cancer patients' group as compared to the non-diabetic subset. The odds ratio for the association between diabetes and risk of developing breast cancer was elevated with statistical significance (OR = 2.96; 95 % CI =1.3-6.3; p-value=0.004). The results of our study showed that diabetes is associated with a risk of developing breast cancer, especially in postmenopausal women (OR = 4.928; 95 % CI = 2.1-11.3; p-value=0.001). The association was particularly marked in obese subjects (OR = 31.49; 95 % CI = 1.8-536; p- value=0.01), as compared to non-obese subjects (OR = 0.642; 95 % CI = 0.2-1.7). Conclusions: Diabetes is strongly associated with obesity and it tends to increase the risk of breast Cancer, especially in postmenopausal women. A high-risk subset for breast cancer comprised postmenopausal, diabetic and overweight women.

Sonoi, Mika;Kayashita, Jun;Yamagata, Yoshie;Tanimoto, Keiji;Miyamoto, Ken-ichi;Sakurama, Kazufumi 3259

https://doi.org/10.14456/apjcp.2016.85/APJCP.2016.17.7.3259 KSCI

Aims: To determine suitable food textures for videofluoroscopic study of swallowing (VFSS), in order to predict and prevent subsequent aspiration pneumonia in esophageal cancer patients with dysphagia after surgery. Materials and Methods: We evaluated 45 hospitalized esophageal cancer patients who underwent surgery between January 2012 and December 2013. The control group consisted of 43 patients treatmed from January 2010 until December 2011 and were not examined by VFSS. Test foods, which were presented in order of increasing thickness, included thin barium sulfate (Ba) liquid (3 or 10 ml), slightly thickened Ba liquid (3 or 10 ml), a spoonful of Ba jelly, and a spoonful of Ba puree. Results: Patients could most safely swallow puree, followed by jelly. The 3-mL samples of both the thin and thick liquids put patients at risk for aspiration pneumonia, with incidence rates of 13% and 11%, respectively. While 64.4% of patients could swallow all test foods and liquids safely, 35.6% were at risk for aspiration pneumonia when swallowing liquids. Even though >30% of patients were at risk, only 1 (2.2%) in the VFSS group developed aspiration pneumonia, which occurred at the time of admission. Following VFSS, no incidence of aspiration pneumonia was observed. However, aspiration pneumonia occurred in 4 (9.3%) control patients during hospitalization. Conclusions: Postoperative esophageal cancer patients were more likely to aspirate any kind of liquid than solid foods, such as jellies. VFSS is very useful in determining suitable food textures for postoperative esophageal cancer patients.

Vardanjani, Hossein Molavi;Heidari, Mohammad;Hadipour, Maryam 3265

https://doi.org/10.14456/apjcp.2016.86/APJCP.2016.17.7.3265 KSCI

Background: Around half of input data in the global burden of disease cancer collaboration (GBD-CC) and GLOBOCAN projects come from low quality sources, mainly from developing countries. This may lead to loss of precision in estimates. Our question was: Are the absolute values and trends of the GBD-CC and GLOBOCAN estimates for lung cancer (LC) in Iran consistent with available statistics?. Materials and Methods: Incidence and mortality statistics were extracted from national reports (N.IRs & N.MRs) and GBD-CC (GBD-incidence & mortality) and GLOBOCAN databases for 1990-2013 where available. Trends were analyzed and absolute values and annual percentage changes (APCs) were estimated and compared. Incompleteness of case ascertainment at the Iranian national cancer registry and Iranian national civil registration was assessed for better understanding. Results: Trends of N.IRs were significantly rising for males (APC: 19.4; 95% CI: 12.5-26.7) and females (23.2; 16.0-30.8). Trends of GBD-incidence were stable for males (-0.2; -1.5-1.1) and females (-1.0; -2.3-0.4). Absolute N.IRs were less than GBD-incidence steadily except for 2009. Trend of N.MRs was increasing up to 2004, but stable thereafter. Trends of GBD-mortality were also stable. Absolute N.MRs were less than GBD-mortality for years up to 2003 and more than GBD-mortality since 2005. The estimates of GLOBOCAN were more than N.IRs and N.MRs. Conclusions: The GBD-CC and GLOBOCAN values for LC in Iran are underestimates. Generation of data quality indices to present along with country specific estimates is highly recommended.

Puataweepong, Putipun;Dhanachai, Mantana;Hansasuta, Ake;Saetia, Kriangsak;Dangprasert, Somjai;Sitathanee, Chomporn;Yongvithisatid, Pornpan 3271

https://doi.org/10.14456/apjcp.2016.87/APJCP.2016.17.7.3271 KSCI

Background: Intracranial nonvestibular schwannomas arising from various cranial nerves excluding CN VIII are uncommon. Recently, stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (SRT) have been widely reported as effective treatment modalities for nonvestibular schwannomas. The purpose of this study was to study the long term clinical outcome for nonvestibular schwannomas treated with both X-Knife and CyberKnife (CK) radiosurgery at one institution. Materials and Methods: From 2004 to 2013, fifty-two nonvestibular schwannoma patients were included in this study, 33 patients (63%) were treated with CK, and 19 (37%) were treated with X-Knife. The majority of the tumors were jugular foramen schwannomas (38%) and trigeminal schwannomas (27%). HSRT was given for 45 patients (86%), whereas CSRT was for 6 (12%) and SRS for 1 (2%). Results: The median pretreatment volume was $9.4cm^3$ (range, $0.57-52cm^3$). With the median follow up time of 36 months (range, 3-135), the 3 and 5 year progression free survival was 94 % and 88%, respectively. Tumor size was decreased in 13 (25%), stable in 29 (56%), and increased in 10 (19%). Among the latter, 3 (30%) required additional treatment because of neurologic deterioration. No patient was found to develop any new cranial nerve deficit after SRS/SRT. Conclusions: These data confirmed that SRS/SRT provide high tumor control rates with low complications. Large volume tumors and cystic expansion after radiation should be carefully followed up with neurological examination and MRI, because it may frequently cause neurological deterioration requiring further surgery.

Haghighi, Shirin;Kasbkar, Hadi;Esmaeilpour, Keihan;Yasaei, Mehrdad 3277

https://doi.org/10.14456/apjcp.2016.88/APJCP.2016.17.7.3277 KSCI

Background: Gastric cancer is considered the fourth most common cancer and second most common cause of cancer-related mortalities worldwide. Gastric cancer develops more frequently among elderly. The oxaliplatin/5FU/leucovorin (FOLFOX) regimen has shown a notable activity against gastric cancer. Aim: To evaluate the responses and complications of FOLFOX-4 regimen as first line chemotherapy in elderly patients with advanced gastric cancer. Materials and Methods: From October 2014 to November 2015, a total of 21 patients with metastatic or local AGC (advanced gastric cancer) were analyzed. All patients were administered a FOLFOX-4 regimen consisting of a 2h infusion of oxaliplatin $85mg/m^2$ (day 1), continuous infusion of $1000mg/m^2$ 5-Fu in 24h., and leucovorin $200mg/m^2$ in 2h infusion as a first-line chemotherapy. Results: A total of 18 patients were assessable for efficacy and toxicity. One of 18 patients achieved a complete response, and 12 had partial responses, giving an overall response rate of 72.6%. Three (16%) patients demonstrated stable disease and 2 (12%) progression. The median progression free survival was 7.3 months, and the median overall survival was 11.9 months. One patient had grade 3 neuropathy. No other grade 3 or 4 NCI-CTC were seen. Conclusions: The FOLFOX-4 regimen used in our study was both active and acceptable for AGC in elderly patients as neoadjuvant and main therapy.

Banjerdpongchai, Ratana;Khaw-on, Patompong;Pompimon, Wialrt 3281

https://doi.org/10.14456/apjcp.2016.89/APJCP.2016.17.7.3281 KSCI

Bioactive compounds extracted from leaves and twigs of Goniothalamus griffithii include pinocembrin (PCN) and goniothalamin (GTN). The objectives of this study were to investigate the cytotoxic activities of PCN and GTN and their influence on molecular signaling for cell death in several human cancer cell lines compared to normal murine fibroblast NIH3T3 cells. GTN exhibited the most potent cytotoxicity against MCF-7 > HeLa > HepG2 > NIH3T3 cells with $IC_{50}$ values of 7.33, 14.8, 37.1 and $65.4{\mu}M$, respectively, whereas PCN was cytotoxic only to HepG2 cells with $IC_{50}$ values of ${\sim}80{\mu}M$. Apoptotic cell death was confirmed by staining the cells with annexin V-FITC and propidium iodide (PI) employing flow cytometry. Apoptosis was shown by externalization of phosphatidylserine in goniothalamin-treated MCF-7 cells in a dose response manner. Positive PI-stained cells with the typical morphology of apoptotic cells were increased dose-dependently. Furthermore, reduction of mitochondrial transmembrane potential was found in goniothalamin-treated MCF-7, HepG2 and HeLa cells. GTN treatment in MCF-7 increased caspase-3, -8 and -9 activities while GTN-induced HeLa cells showed an increase of both caspase-3 and -9 activities. But an increased caspase-8 activity was demonstrated in GTN- and PCN-treated MCF-7 and HepG2 cells, respectively. Taken together, GTN- and PCN-induced human cancer cell apoptosis was through different molecular mechanisms or signaling pathways, which might be due to different machineries in different types of cancer cells, as evidenced by the compound-modulated caspase activities in both intrinsic and/or extrinsic pathways.

Banjerdpongchai, Ratana;Wudtiwai, Benjawan;Khaw-on, Patompong 3289

https://doi.org/10.14456/apjcp.2016.90/APJCP.2016.17.7.3289 KSCI

Naringin, a bioflavonoid found in Citrus seeds, inhibits proliferation of cancer cells. The objectives of this study were to investigate the mode and mechanism(s) of hepatocellular carcinoma HepG2 cell death induced by naringin. The cytotoxicity of naringin towards HepG2 cells proved dose-dependent, measured by MTT assay. Naringin-treated HepG2 cells underwent apoptosis also in a concentration related manner, determined by annexin V-fluorescein isothiocyanate (FITC) and propidium iodide (PI) employing flow cytometry. Mitochondrial transmembrane potential (MTP) measured using 3,3'-dihexyloxacarbocyanine iodide ($DiOC_6$) and flow cytometer was reduced concentration-dependently, which indicated influence on the mitochondrial signaling pathway. Caspase-3, -8 and -9 activities were enhanced as evidenced by colorimetric detection of para-nitroaniline tagged with a substrate for each caspase. Thus, the extrinsic and intrinsic pathways were linked in human naringin-treated HepG2 cell apoptosis. The expression levels of pro-apoptotic Bax and Bak proteins were increased whereas that of the anti-apoptotic Bcl-xL protein was decreased, confirming the involvement of the mitochondrial pathway by immunoblotting. There was an increased expression of truncated Bid (tBid), which indicated caspase-8 proteolysis activity in Bid cleavage as its substrate in the extrinsic pathway. In conclusion, naringin induces human hepatocellular carcinoma HepG2 cell apoptosis via mitochondria-mediated activation of caspase-9 and caspase-8-mediated proteolysis of Bid. Naringin anticancer activity warrants further investigation for application in medical treatment.

Abdelaal, Shereen E;Habib, Fahima M;el Din, Amina A Gamal;Gabal, Samia M;Hassan, Nabila S;Ibrahim, Nihad A 3295

https://doi.org/10.14456/apjcp.2016.91/APJCP.2016.17.7.3295 KSCI

Background: Different types of cancer exhibit abnormalities in cell cycle regulators. The murine double minute-2(MDM2) cell cycle regulator is a proto-oncogene that negatively regulates the P53 tumour suppressor gene. Surface epithelial tumours constitute approximately two thirds of ovarian neoplasms. Each histologic type can be classified as benign, borderline and malignant. This study aimed to examine immunohistochemical expression of the MDM2 protein in ovarian serous and mucinous epithelial tumours (benign, borderline and malignant). Materials and Methods: This study included forty five ovarian tumours, subdivided into fifteen cystadenomas (5 serous and 10 mucinous), fifteen borderline tumours (11 serous and 4 mucinous) and fifteen cystadenocarcinomas (9 serous and 6 mucinous). Paraffin sections were stained with haematoxylin and eosin for histopathologic study, and with mouse monoclonal anti-MDM2 antibody for immunohistochemistry. Results: MDM2 positivity was detected in 28.9% of the studied ovarian tumours. All benign tumours were negative and positivity was significantly higher in malignant than borderline tumours (P value of chi-square test =0.000). Significantly, all MDM2 positive mucinous tumours were malignant with no positive mucinous borderline tumours. Malignant tumours showed positive MDM2 expression in 83.3% of mucinous type and in 55.6% of serous type. Borderline serous tumours showed negative MDM2 in 72.7% of cases (P value of Z test =0.04). Conclusions: Alterations in the expression of the cell cycle regulator (MDM2) occur early in the process of tumourigenesis in serous and mucinous ovarian tumours. We suggest that MDM2 may be used in those tumours as a marker for risk stratification and identification of cases with cancer development and progression. We recommend further studies on MDM2 immunohistochemistry, in conjunction with adjuvant methods as DNA ploidy and FISH gene amplification, focusing on the mucinous tumours and differentiating between the three tumour categories, benign, borderline and malignant.

Park, Kyoung-Ok;Kang, Jina 3301

https://doi.org/10.14456/apjcp.2016.92/APJCP.2016.17.7.3301 KSCI

Background: Cancer is a leading cause of death in Korea. To prevent cancer, it is essential to facilitate and promote appropriate cancer screening behavior in the adult population. The aim of this study was to examine health beliefs related to cancer screening intentions using the Health Belief Model (HBM). Materials and Methods: The research participants comprised 275 male health and safety managers at commercial companies in Korea. The self-administered survey explored demographic characteristics, cancer-related factors, beliefs about cancer/cancer screening (BCCS) (vulnerability to cancer, severity of cancer, benefits of screening, and barriers to screening), and cancer screening intention. Multivariate logistic regression analyses were used to identify factors associated with an intention to be screened for cancer. Results: Perceived health status and need for cancer prevention education were major factors associated with BCCS. Poorer health status was associated with greater perceived vulnerability, a perception of fewer benefits, and more barriers (p<0.05). A perceived greater need for cancer prevention education was associated with a higher perceived severity of cancer and more perceived barriers to screening (p<0.05). Marital status, cancer screening experience, and perceived vulnerability to cancer were significant influences on the cancer screening intention (p<0.05). Participants who had undergone cancer screening in the past 2 years were more likely to intend to be screened for cancer than were those who had not been screened; this was true across all degrees of intention and all types of cancer (p<0.01). Hesitant people considered themselves less vulnerable to gastric, lung, and liver cancer than did the poeple who intended to undergo cancer screening (p<0.05). Conclusions: Based on our findings, we recommend that workplace cancer prevention programs attempt to increase awareness about vulnerability to cancer among workers who hesitate to undergo cancer screening.

Goudarzi, Mehdi;Seyedjavadi, Sima Sadat;Fazeli, Maryam;Roshani, Maryam;Azad, Mehdi;Heidary, Mohsen;Navidinia, Masoumeh;Goudarzi, Hossein 3309

https://doi.org/10.14456/apjcp.2016.93/APJCP.2016.17.7.3309 KSCI

Helicobacter pylori as the second most common cause of gastric cancer in the world infects approximately half of the developed countries population and 80% of the population living in developing countries. Integrons as genetic reservoirs play major roles in dissemination of antimicrobial resistance genes. To the best of our knowledge, this is the first study to report carriage of class 1 and 2 integrons and associated gene cassettes in H. pylori isolates from Iran. This cross-sectional study was conducted in Tehran among 110 patients with H. pylori infection. Antimicrobial susceptibility testing (AST) for H. pylori strains were assessed by the micro broth dilution method. Class 1 and 2 integrons were detected using PCR. In order to determine gene cassettes, amplified fragments were subjected to DNA sequencing of both amplicon strands. The prevalence of resistance to clarithromycin, metronidazole, clarithromycin, tetracycline, amoxicillin, rifampin, and levofloxacin were 68.2% (n=75), 25.5% (n=28), 24.5% (n=27), 19.1% (n=21), 18.2% (n=20) and 16.4% (n=18), respectively. Frequency of multidrug resistance among H. pylori isolates was 12.7%. Class 2 integron was detected in 50 (45.5%) and class 1 integron in 10 (9.1%) H. pylori isolates. The most predominant gene cassette arrays in class 2 integron-bearing H. pylori were included sat-era-aadA1, dfrA1-sat2-aadA1, blaoxa2 and, aadB whereas common gene cassette arrays in class 1 integron were aadB-aadA1-cmlA6, aacA4, blaoxa2, and catB3. The high frequency of class 2 integron and multidrug resistance in the present study should be considered as a warning for clinicians that continuous surveillance is necessary to prevent the further spread of resistant isolates.

Senol, Taylan;Polat, Mesut;Ozkaya, Enis;Karateke, Ates 3317

https://doi.org/10.14456/apjcp.2016.94/APJCP.2016.17.7.3317 KSCI

Purpose: To assess the success rates of two step loop electrosurgical excision procedure (LEEP) compared with conventional cold conization procedures for decreasing positive surgical margins. Materials and Methods: This study was conducted on 70 patients who underwent colposcopic evaluation in Zeynep Kamil Women and Children's Health Training and Research Hospital between 2013-2015 with indications of CIN 2/3 or persistent CIN 1 for more than 2 years. The study included age matched groups of patients with similar histopathololical lesions who underwent cold conization (n=40) or LEEP (N=30). Results: Comparison of tissue characteristics between the two groups revealed significantly higher deepest depth and lower volume of tissue removed by the two step LEEP. Ectocervical positivity rate was similar between groups (1/39 versus 0/29, P>0.05), while endocervical surgical margin positivity rate was significantly higher in the cold conization group (9/39 versus 0/29, P<0.05). Surgical margin positive cases were significantly older than the cases with negative margins (P<0.05). Conclusions: Two step LEEP made it easier to reach the squamocolumnar junction in the endocervical region with lower blood loss and applicability in office settings. Our study suggests to use two step approach in cases with high grade and glandular CIN.

Payandeh, Mehrdad;Shazad, Babak;Madani, Seyed-Hamid;Ramezani, Mazaher;Sadeghi, Masoud 3321

https://doi.org/10.14456/apjcp.2016.95/APJCP.2016.17.7.3321 KSCI

Background: Androgen receptors (ARs) are expressed in more than 70% of breast cancers (BCs) and have been implicated in BC pathogenesis. Some triple negative (TN)BC tumors express AR and may benefit from AR-targeted therapies. The aim of this study was to evaluate survival and the prevalence of AR expression and its correlation with other risk factors in triple negative BCs in women from Western Iran. Materials and Methods: In a retrospective study between 2009-2015, 41 patients with TNBC were referred to the Private Clinic of Oncology, Kermanshah city, Iran. ER, PR and AR-positive expression was defined as ${\geq}10%$ nuclear staining and also HER2 (2+), FISH was performed. Nuclear staining was considered representative for Ki67 and P53. The mean follow-up for the patients was 25 months. In this time, 5 patients died and 4 lost to follow-up were censored from survival analysis. Results: The mean age at diagnosis was 46.9 years (range, 24-71 years) and all patients were female. The OS rates for AR-positive and AR-negative patients were 90% and 85.1%, respectively, and the mean OS was 26.3 and 23.2 months. Therefore, there was no significant difference between the two groups (Hazard ratio: 0.580, 95% CI: 0.086-3.893, P=0.575). Conclusions: In TNBC patients, evaluation of AR status may provide additional information on prognosis and treatment. The results of studies showed that the prevalence AR expression may differ in the world and probably ethnicity can be an influencing factor.

Lim, Geok-Hoon;Pineda, Lea Angela 3325

https://doi.org/10.14456/apjcp.2016.96/APJCP.2016.17.7.3325 KSCI

Background: There are limited studies on oncoplastic breast conserving surgery in Asian women. We aimed to determine the applicability and safety of oncoplastic surgery, highlighting the specific circumstances when it will be most useful and compare our preferred technique with the worldwide practice of oncoplastic approaches. Materials and Methods: Breast cancer patients who underwent oncoplastic breast conserving surgery at a single institution from 1st May 2014-31st March 2015 were included. Data on patient demographics, tumor characteristics and the type of oncoplastic surgery performed were collected. Results: Nineteen breast cancer patients were identified. 42.1% of patients had grade I ptosis. The indications for surgery included a large tumor to breast size ratio (52.6%), multifocal/multicentric lesions (36.8%) and asymmetric breasts (10.6%), averting a mastectomy in 89.4%. Round block was the commonest technique in 63% of patients, in contrast to the inverted T pattern most frequently used in renowned institutions in the West. Mean and median tumor size and weight of specimen were 29.4/25mm (11 - 75mm) and 77g/64g (10 - 246g) respectively. Re-excision rate was 10.5%. Complete mastectomy was performed for one patient. One patient developed wound dehiscence which was treated conservatively. Cosmetic outcome was rated as excellent/good by 94.7% of patients. The patients remained clinically well after a median 16 months follow up. Conclusions: Oncoplastic breast conserving surgery is useful in a specific subgroup of Asian patients with a relatively small breast volume and minimal ptosis. Round block was the commonest technique in our series, in contrast to the worldwide utility of oncoplastic techniques. It is oncologically safe and has good cosmetic outcomes.

Hegazy, Wael Abdel Halim;Youns, Mahmoud 3329

https://doi.org/10.14456/apjcp.2016.97/APJCP.2016.17.7.3329 KSCI

Cancer is thought to be a direct result of transcriptional misregulation. Broad analysis of transcriptional regulatory elements in healthy and cancer cells is needed to understand cancer development. Nucleases regulatory domains are recruited to bind and manipulate a specific genomic locus with high efficacy and specificity. TALENs (transcription activator-like effector nuclease) fused to endonuclease FokI have been used widely to target specific sequences to edit several genes in healthy and cancer cells. This approach is promising to target specific cancer genes and for this purpose it is needed to pack such TALENs into viral vectors. There are some considerations which control the success of this approach, targeting appropriate sequences with efficient construction of TALENs being crucial factors. We face some obstacles in construction of TALENs; in this study we made a modification to the method of Cermk et al 2011 and added one step to make it easier and increase the availability of constructs.

Yaming, Punyo;Urs, Aadithya Basavaraj;Saxena, Alpana;Zuberi, Mariyam 3335

https://doi.org/10.14456/apjcp.2016.98/APJCP.2016.17.7.3335 KSCI

Background: Oral submucous fibrosis (OSF) is a precancerous condition with a 4 to13% malignant transformation rate. Related to the habit of areca nut chewing it is mainly prevalent in South-east Asian countries where the habit of betel quid chewing is frequently practised. On chewing, alkaloids and polyphenols are released which undergo nitrosation and give rise to N-nitrosamines which are cytotoxic agents. CYP450 is a microsomal enzyme group which metabolizes various endogenous and exogenous chemicals including those released by areca nut chewing. CYP1A1 plays a central role in metabolic activation of these xenobiotics, whereas CYP2E1 metabolizes nitrosamines and tannins. Polymorphisms in genes that code for these enzymes may alter their expression or function and may therefore affect an individuals susceptibility regarding OSF and oral cancer. The present study was therefore undertaken to investigate the association of polymorphisms in CYP1A1 m2 and CYP2E1 (RsaI/PstI) sites with risk of OSF among areca nut chewers in the Northern India population. A total of 95 histopathologically confirmed cases of OSF with history of areca nut chewing not less than 1 year and 80, age and sex matched controls without any clinical signs and symptoms of OSF with areca nut chewing habit not less than 1 year were enrolled. DNA was extracted from peripheral blood samples and polymorphisms were analyzed by PCR-RFLP method. Gene polymorphism of CYP1A1 at NcoI site was observed to be significantly higher (p = 0.016) in cases of OSF when compared to controls. Association of CYP1A1 gene polymorphism at NcoI site and the risk of OSF (Odd's Ratio = 2.275) was also observed to be significant. However, no such association was observed for the CYP2E1 gene polymorphism (Odd's Ratio = 0.815). Our results suggest that the CYP1A1 gene polymorphism at the NcoI site confers an increased risk for OSF.

Talip, Tajidah;Murang, Zaidah;Kifli, Nurolaini;Naing, Lin 3341

https://doi.org/10.14456/apjcp.2016.99/APJCP.2016.17.7.3341 KSCI

Background: A recent WHO data report on mortality attributable to tobacco use including cigarette smoking indicated a very high burden of deaths in Asia and that people often initiate smoking as early as young adolescents. The objectives of this study were to systematically review peer-reviewed articles on cigarette smoking initiation among Asian adolescents and to develop a conceptual model of factors influencing smoking initiation by integrating all relevant factors based on existing data. Materials and Methods: Following a PRISMA guideline, a systematic review of articles published between 2005 and June 2015 was conducted using 5 databases on cigarette smoking initiation among adolescents (aged 10-19 years) living in Asia. We summarized the main findings of each study according to our research questions and data that emerged during the data extraction process. Analysis and categorization were based on the TTI and TPB models and classification of factors extracted from the study, were as follows: personal factors, social factors, broader environmental factors, mediators, and intention to initiate smoking and smoking behavior. Results: Of 1,227 identified studies, only 20 were included in this review. Our findings found that the mean age of cigarette smoking initiation ranged from 10 to 14 years and those who are more likely to initiate smoking are male, older adolescents, adolescents with low parental SES, individuals with low parental monitoring, low parental education level and having no discussion on smoking at home, those living in public housing and those exhibiting health-risk behavior. Our study also revealed that the risk of smoking initiation increased when they are exposed to smokers, influenced by peers, exposed to tobacco advertisements, receive pocket money, have lack of knowledge about smoking, have poor school performance, have a family conflict and have psychological problems. The conceptual model developed demonstrated complex networks of factors influencing initiation. Conclusions: This systematic review presents various factors influencing smoking initiation of the Asian adolescents and provides a conceptual framework to further analyze factors. Future studies should have a standard measure of smoking initiation, should analyze interactions and the intensity of relationships between different factors or variables in the conceptual model. This will in turn consolidate the understanding of the different factors affecting smoking initiation and will help to improve interventions in this area.

Cho, Kyung Eun;Gweon, Hye Mi;Park, Ah Young;Yoo, Mi Ri;Kim, Jeong-Ah;Youk, Ji Hyun;Park, Young Mi;Son, Eun Ju 3357

https://doi.org/10.14456/apjcp.2016.100/APJCP.2016.17.7.3357 KSCI

Purpose: To correlate ultrasonographic (US) features of medullary thyroid carcinoma (MTC) with preoperative and post-operative calcitonin levels. Materials and Methods: A total of 130 thyroid nodules diagnosed as MTC were evaluated. Two radiologists retrospectively evaluated preoperative US features according to size, shape, margin, echogenicity, type of calcification, and lymph node status. Postoperative clinical and imaging follow-up (mean duration $31.9 {\pm} 22.5$ months) was performed for detection of tumor recurrence. US features, presence of LN metastasis, and tumor recurrence were compared between MTC nodules with and without elevated preoperative calcitonin (>100 pg/mL). Those with normalized and non-normalized postoperative calcitonin levels groups were also compared. Results: Common US features of MTCs were solid internal content (90.8%), irregular shape (44.6%), circumscribed margin (46.2%), and hypoechogenicity (56.2%). Comparing MTC nodules with and without elevated preoperative calcitonin levels, the size and shape of MTC nodule and lymph node metastasis showed statistical significance (p<0.05). Postoperative calcitonin normalization correlated with US features of tumor size (p=0.002), margin (p=0.034), shape ($p{\leq}0.001$), and presence of calcification (p=0.046). Tumor recurrence and LN metastasis were more prevalent in patients without normalization of postoperative calcitonin than in those with normalization (p=0.001). Conclusions: Serum calcitonin measurement is helpful for early diagnosis and predicting prognosis. Postoperative calcitonin measurement is also important for postoperative US follow up, especially in cases with larger nodule size, presence of calcification, irregular shape, and irregular margin.

Shaikh, Fouzia;Jamal, Qamar;Baig, Saeeda;Hadi, Naila Irum;Majeed, Noman 3363

https://doi.org/10.14456/apjcp.2016.101/APJCP.2016.17.7.3363 KSCI

Background: Breast cancer (BC) is a major health issue worldwide as well as in Pakistan. All women belonging to any race, ethnicity or lineage are in danger of developing breast cancer. Significant factors influencing the development of breast malignancies are the genetic background, environmental conditions, reproductive parameters, the consequences of female hormones both intrinsic and extrinsic, alteration of immune status, and biologic determinants. Materials and Methods: Overall 150 biopsy proven patients were included in the study. Samples were submitted for histopathology and determination of estrogen and progesterone receptor expression and HER-2/neu status. Associations with other characteristics like age, tumor stage, node involvement, histological grade were also studied. Results: Mean age at presentation was 46.7 years. The majority had invasive ductal carcinoma, 100 (84.7%), and were in stage pT3, 54 (45.7%). Important relationships (P<0.05) were found among ER, PR positivity, and Her 2 neu overexpression. However, no noteworthy link was identified amongst ER, PR, Her 2 neu and tumor grade, stage, age, lymph node involvement except for the menopausal status. Conclusions: In summary, breast cancer patients featured an advanced stage of disease, more lymph node involvement, and moderately high grade tumors and with more estrogen, progesterone receptor and HER-2 positive tumors.

Toraih, Eman A;Fawzy, Manal S;Elgazzaz, Mona G;Hussein, Mohammad H;Shehata, Rasha H;Daoud, Hisham G 3369

https://doi.org/10.14456/apjcp.2016.102/APJCP.2016.17.7.3369 KSCI

MicroRNAs, a novel class of small non-coding RNAs, are key players in many cellular processes, including cell proliferation, differentiation, invasion and regeneration. Tissue and circulatory microRNAs could serve as useful clinical biomarkers and deregulated expression levels have been observed in various cancers. Gene variants may alter microRNA processing and maturation. Thus, we aimed to investigate the association of MIR-196a2 rs11614913 (C/T), MIR-499a rs3746444 (A/G) polymorphisms and their combination with cancer susceptibility in an Egyptian population. Sixty five renal cell carcinoma (RCC) and 60 hepatocellular carcinoma (HCC) patients and 150 controls were enrolled in the study. They were genotyped using real-time polymerase chain reaction technology. Both $miR-196a2^*T$ and $miR-499a*G$ were associated with RCC risk, but only $miR-196a^*T$ was associated with HCC development. Carriage of the homozygote combinations ($MIR196a2^*TT+MIR499a^*AA$) and ($MIR196a2^*CC+MIR499a^*GG$) was associated with 25 and 48 fold elevation of likelhood to develop RCC, respectively. The miR-196a2 SNP was also linked with larger tumor size in RCC and advanced tumor stage in HCC. miR-196a2 and miR-499a combined genotypes were associated with RCC and HCC. Further functional analysis of SNPs is required to confirm relationships between genotypes and phenotypes.

Igata, Fumiyasu;Uchino, Junji;Fujita, Masaki;Iwasaki, Akinori;Watanabe, Kentaro 3377

https://doi.org/10.14456/apjcp.2016.103/APJCP.2016.17.7.3377 KSCI

The proportion of lung cancer patients under 50 years old is small at approximately 5-10%, but as with patients older than 50, the number is on the rise. Although lung cancer treatment strategies have undergone extensive transformation in recent years based on the presence or absence of oncogenic driver mutations, there are few reports regarding these mutations in the young or the relationship between clinical setting and prognosis. Therefore, we conducted a study of clinical features in 36 patients under the age of 50 who were diagnosed with primary lung cancer from October 2008 to November 2015. The 22 patients in stages I through III A underwent operations, and all 17 whose lung cancer were detected through screening were candidates for surgery. Gene analysis was conducted for 26 (72.2%); 10 (38.5%) were positive for EGFR gene mutations, and ALK gene translocation was present in 4 (15.4%). In stage IV patients, the median progression free survival (PFS) in the ALK translocation positive and negative patients was 518 days and 130 days, respectively, and the median overall survival (OS) was not reached and 280 days, respectively. A trend toward extended PFS (p=0.203) and OS (p=0.056) was observed in patients positive for ALK translocation. We must strive for early detection by increasing screening rates and evaluate oncogenic driver mutations important for prognosis of lung cancer in the young.

Azar, Saleh Shahbazi;Mansoori, Maryam;Attar, Marzieh;Shahbazi, Majid 3381

https://doi.org/10.14456/apjcp.2016.104/APJCP.2016.17.7.3381 KSCI

Background: Hepatitis B virus (HBV) is a key factor for hepatocellular carcinoma (HCC). About 350 million people are affected by chronic infection which is related to the rapid development of liver diseases as well as hepatitis, cirrhosis and hepatocellular carcinoma. Expression of tumor necrosis factor alpha (TNF-${\alpha}$) in the liver demonstrates a major genetic polymorphism which is involved in resistance or susceptibility to chronic HBV infection. Materials and Methods: In this study, two populations were studied by the sequence specific primer-polymerase chain reaction (SSP-PCR) method: HBV cases (n=409), who were HBS-Ag+, and healthy controls (n=483). Results: The results shown that the frequency of TNF-${\alpha}$ -308 G/G genotype in healthy controls (47.2%) was significantly higher than in HBV infected patients (28%) (CI = 1.29-2.61, OR = 1.83, P = 0.0004). Also TNF-${\alpha}$ -308 A/A and A/G genotype frequencies in the healthy controls were 4.6% and 48.2% and in patient group were 19.5% and 52.5% (CI = 2.23-7.12, p: 0.0001, OR: 3.94) respectively. Conclusions: We found that among Iranian people TNF-${\alpha}$ -308A allele not only has the highest genotype frequency but also it has the highest frequency in the world population. In addition, TNF-${\alpha}$-308 G/G polymorphism was associated with HBV resistance, whereas TNF-${\alpha}$-308A (A/A or A/G) polymorphism appeared to associated with chronic HBV infection. These data suggested that among the Iranian population, the -308 G/G polymorphism of TNF-${\alpha}$ gene promoter region has the potential to influence the susceptibility to HBV infection and it may be responsible for viral antigen clearance.

Murray, Nigel P;Reyes, Eduardo;Fuentealba, Cynthia;Jacob, Omar 3385

https://doi.org/10.14456/apjcp.2016.105/APJCP.2016.17.7.3385 KSCI

Background: Sequential use of circulating prostate cell (CPC) detection has been reported to potentially decrease the number of unnecessary prostate biopsies in men suspected of prostate cancer. In order to determine the real world effectiveness of the test, we present a prospective study of men referred to two hospitals from primary care physicians, one using CPC detection to determine the necessity of prostate biopsy the other not doing so. Materials and Methods: Men with a suspicion of prostate cancer because of elevated PSA >4.0ng/ml or abnormal DRE were referred to Hospitals A or B. In Hospital A all underwent 12 core TRUS biopsy, in Hospital B only men CPC (+), with mononuclear cells obtained by differential gel centrifugation identified using double immunomarking with anti-PSA and anti-P504S, were recommended to undergo TRUS biopsy. Biopsies were classifed as cancer or no-cancer. Diagnostic yields were calculated, including the number of posible biopsies that could be avoided and the number of clinically significant cancers that would be missed. Results: Totals of 649 men attended Hospital A, and 552 men attended Hospital B; there were no significant differences in age or serum PSA levels. In Hospital A, 228 (35.1%) men had prostate cancer detected, CPC detection had a sensitivity of 80.7%, a specificity of 88.6%, and a negative predictive value of 89.5%. Some 39/44 men CPC negative with a positive biopsy had low grade small volume tumors. In Hospital B, 316 (57.2%) underwent biopsy. There were no significant differences between populations in terms of CPC and biopsy results. The reduction in the number of biopsies was 40%. Conclusions: The use of sequential CPC testing in the real world gives a clear decision structure for patient management and can reduce the number of biopsies considerably.

Tongtawee, Taweesak;Bartpho, Theeraya;Kaewpitoon, Soraya;Kaewpitoon, Natthawut;Dechsukhum, Chavaboon;Leeanansaksiri, Wilairat;Loyd, Ryan A;Matrakool, Likit;Panpimanmas, Sukij 3391

https://doi.org/10.14456/apjcp.2016.106/APJCP.2016.17.7.3391 KSCI

Background: Helicobacter pylori is now recognized as a causative factor of chronic gastritis, gastroduodenal ulcers, gastric cancer and mucosa-associated lymphatic tissue lymphoma. Toll-like receptors are important bacterial receptors in gastric epithelial cell signaling transduction and play critical roles in gastric carcinogenesis. Materials and Methods: A total of 400 patients undergoing esophagogastroduodenoscopy for investigation of chronic abdominal pain were genotyped for single-nucleotide polymorphisms (SNPs) in TLR1 (rs4833095) using TagMan SNPs genotyping assay by real-time PCR hybridization. Relationships with susceptibility to H. pylori infection and pre-malignant gastric mucosa morphological patterns, classified by magnifying NBI endoscopy, were investigated. Results: The percentages of TLR1 rs4833095, CC homozygous, CT heterozygous and TT homozygous cases were 34, 46.5 and 19%, respectively. CC showed statistical differences between H. pylori positive and negative cases (P<0.001). CT and TT correlated with type 1 and type 2 gastric mucosal morphological patterns (P <0.01) whereas CC correlated with types 3 and 4 (P<0.01). Conclusions: This study demonstrated good correlation of TLR1 rs4833095 genotype with severity of inflammation in H. pylori infected gastric mucosa according to gastric mucosal morphologic patterns with magnifying NBI endoscopy.

Kadirareddy, Rashmi Holur;GhantaVemuri, Sujana;Palempalli, Uma Maheswari Devi 3395

https://doi.org/10.14456/apjcp.2016.107/APJCP.2016.17.7.3395 KSCI

Conjugated linoleic acid, a functional lipid, produced from Lactobacillus plantarum (LP-CLA), has been demonstrated to possess apoptotic activity. The anti-proliferative and apoptotic potential of LP-CLA was here evaluated in vitro using the MDA-MB-231 human breast cancer cell line as a model system. Proliferation of MDA-MB-231 cells was inhibited with increasing concentrations of LP-CLA with altered morphological features like cell detachment, rounding of cells and oligonucleosomal fragmentation of DNA. Flow cytometry confirmed the apoptotic potential of LP-CLA by ANNEXIN V/PI double staining. Furthermore, outcome results indicated that the apoptosis was mediated by downregulation of the NF-${\kappa}B$ pathway which in turn acted through proteasome degradation of $I{\kappa}B{\alpha}$, inhibition of p65 nuclear translocation, release of cytochrome-C from mitochondria and finally overexpression of Bax protein. Thus, conjugated linoleic acid, a natural product derived from probiotics, could therefore be a possible potential chemotherapeutic agent due to its apoptotic activity against estrogen receptor negative breast cancer cells.

Tabata, Chiharu;Tabata, Rie;Nakano, Takashi 3405

https://doi.org/10.14456/apjcp.2016.108/APJCP.2016.17.7.3405 KSCI

Malignant pleural mesothelioma (MPM), an aggressive malignant tumor of mesothelial origin associated with asbestos exposure, shows a limited response to conventional chemotherapy and radiotherapy. Therefore, the overall survival of MPM patients remains very poor. Progress in the development of therapeutic strategies for MPM has been limited. We recently reported that the calpain inhibitor, calpeptin exerted inhibitory effects on pulmonary fibrosis by inhibiting the proliferation of lung fibroblasts. In the present study, we examined the preventive effects of calpeptin on the cell growth of MPM, the origin of which is mesenchymal cells, similar to lung fibroblasts. Calpeptin inhibited the proliferation of MPM cells, but not mesothelial cells. It also prevented 1) the expression of angiopoietin (Ang)-1 and Tie-2 mRNA in MPM cells, but not mesothelial cells and 2) the Ang-1-induced proliferation of MPM cells through an NF-kB dependent pathway, which may be the mechanism underlying the preventive effects of calpeptin on the growth of MPM cells. These results suggest potential clinical use of calpeptin for the treatment of MPM.

Borthakur, Parikhit;Kataki, Kangkana;Keppen, Chenole;Khamo, V.;Medhi, Subhash;Deka, Manab 3411

https://doi.org/10.14456/apjcp.2016.107/APJCP.2016.17.7.3411 KSCI

Background: Nasopharyngeal carcinoma (NPC), a malignancy arising from the epithelial lining of the nasopharynx, is distinct from others cancers in terms of its epidemiologic features. It is rare in most parts of the world except for a few regions with populations of Mongoloid origin. Objectives: To study the expression pattern of Epstein Barr virus (EBV) encoded oncoproteins EBNA1 and LMP1 in different histological types of NPC and to correlate expression patterns with sex, age and histological types. Materials and Methods: A total of 40 formalin-fixed, paraffin-embedded NPC biopsy samples and tissues from 20 healthy controls were collected to study the expression level of EBNA1 and LMP1 using immunohistochemistry. Results: EBNA1 and LMP1 expression was found in 92.5% and 90% respectively, of the cases and none of the control specimens. The expression patterns of EBNA1 and LMP1 were determined to be statistically significant (p<0.05) when correlated with sex, age and histological distributions. Also immunohistochemistry was found to be a sensitive technique in the detection of EBV. Conclusions: The study reveals that the potent oncoproteins EBNA1 and LMP1 were over expressed in our population cohort. Our findings are to some extent inconsistent with earlier reports as our population showed a higher expression of both EBNA1 and LMP1 compared to other studies.

Prachanukool, Thidathit;Tangkulpanich, Panvilai;Paosaree, Possawee;Sawanyawisuth, Kittisak;Sitthichanbuncha, Yuwares 3423

https://doi.org/10.14456/apjcp.2016.111/APJCP.2016.17.7.3423 KSCI

Background: Sepsis is an emergency condition with high mortality and morbidity rate. There are limited data on the association of cancer as a risk factor for mortality in sepsis patients in the emergency department (ED). Materials and Methods: This retrospective study was conducted at the ED, Faculty of Medicine, Ramathibodi Hospital, Bangkok, Thailand. The study period was between January 1st and December $31^{st}$, 2014. The inclusion criteria were as follows: adult patients over 15 years of age who presented at the ED with suspicion of sepsis, received treatment at the ED, and whose blood culture was found to be positive. Clinical data were recorded from medical records including the Mortality in Emergency Department Sepsis score (MEDS score). The primary outcome of this study was mortality at one month. Multivariate logistic regression analysis was used to identify independent factors associated with death. Results: During the study period, there were 775 eligible patients. The two most common pathogens identified from blood cultures were Staphylococcus aureus (193 patients; 24.9%) and Escherichia coli (158 patients; 20.4%). At one month after presenting at the ED, 110 patients (14.2%) had died. There were four significant factors for death, having cancer, being on an endotracheal tube, initial diagnosis of bacteremia, and high MED scores. Having cancer had an adjusted OR of 2.12 (95% CI of 1.29, 3.47). Conclusions: Cancer patients have double the risk of mortality if presenting with sepsis at the ED.

Singh, Richa;Bhatt, Madan Lal Brahma;Singh, Saurabh Pratap;Kumar, Vijay;Goel, Madhu Mati;Mishra, Durga Prasad;Srivastava, Kirti;Kumar, Rajendra 3431

https://doi.org/10.14456/apjcp.2016.113/APJCP.2016.17.7.3431 KSCI

Background: Carcinogenesis is a multifaceted intricate cellular mechanism of transformation of the normal functions of a cell into neoplastic alterations. Metastasis may result in failure of conventional treatment and death Hence, research on metastatic suppressors in cancer is a high priority. The metastatic suppressor gene CD82, also known as KAI1, is a member of the transmembrane 4 superfamily which was first identified in carcinoma of prostate. Little work has been done on this gene in breast cancer. Herein, we aimed to determine the gene and protein level expression of CD82/KAI1 in breast cancer and its role as a prognosticator. Materials and Methods: In this study, 83 histologically proven cases of breast cancer and a similar number of controls were included. Patient age ranged from 18-70 years. Quantitative Real Time Polymerase Chain Reaction (q-RT PCR) and immunohistochemistry (IHC) were used to investigate KAI1 expression at gene and protein levels, respectively. Statistical analysis was done to correlate expression of KAI1 and clinicopathological parameters. Results: It was revealed that: (i) KAI1 was remarkably diminished in metastatic vs non metastatic breast cancer both at the gene and the protein levels (P < .05); (ii) KAI1 expression levels were strongly correlated with TNM staging, histological grade and advanced stage (p<0.001) and no association was found with any other studied parameter; (iii) Lastly, a significant correlation was observed between expression of KAI1 and overall median survival of BC patients (P = 0.04). Conclusions: Our results suggest that lack of expression of the KAI1 might indicate a more aggressive form of breast cancer. Loss of KAI1 may be considered a significant prognostic marker in predicting metastatic manifestation. When evaluated along with the clinical and pathological factors, KAI1 expression may be beneficial to tailor aggressive therapeutic strategies for such patients.

Mohamad, Maisarah;Wahab, Norhazlina Abdul;Yunus, Rosna;Murad, Nor AzianAbdul;Zainuddin, Zulkifli Md;Sundaram, Murali;Mokhtar, Norfilza Mohd 3437

https://doi.org/10.14456/apjcp.2016.114/PJCP.2016.17.7.3437 KSCI

Background: There is an increasing concern in the role of microRNA (miRNA) in the pathogenesis of bone metastasis (BM) secondary to prostate cancer (CaP). In this exploratory study, we hypothesized that the expression of vinculin (VCL) and chemokine X3C ligand 1 (CX3CL1) might be down-regulated in clinical samples, most likely due to the post-transcriptional modification by microRNAs. Targeted genes would be up-regulated upon transfection of the bone metastatic prostate cancer cell line, PC3, with specific microRNA inhibitors. Materials and Methods: MicroRNA software predicted that miR-21 targets VCL while miR-29a targets CX3CL1. Twenty benign prostatic hyperplasia (BPH) and 16 high grade CaP formalin-fixed paraffin embedded (FFPE) specimens were analysed. From the bone scan results, high grade CaP samples were further classified into CaP with no BM and CaP with BM. Transient transfection with respective microRNA inhibitors was done in both RWPE-1 (normal) and PC3 cell lines. QPCR was performed in all FFPE samples and transfected cell lines to measure VCL and CX3CL1 levels. Results: QPCR confirmed that VCL messenger RNA (mRNA) was significantly down-regulated while CX3CL1 was up-regulated in all FFPE specimens. Transient transfection with microRNA inhibitors in PC3 cells followed by qPCR of the targeted genes showed that VCL mRNA was significantly upregulated while CX3CL1 mRNA was significantly down-regulated compared to the RWPE-1 case. Conclusions: The down-regulation of VCL in FFPE specimens is most likely regulated by miR-21 based on the in vitro evidence but the exact mechanism of how miR-21 can regulate VCL is unclear. Up-regulated in CaP, CX3CL1 was found not regulated by miR-29a. More microRNA screening is required to understand the regulation of this chemokine in CaP with bone metastasis. Understanding miRNA-mRNA interactions may provide additional knowledge for individualized study of cancers.

Tamrakar, D;Paudel, IS;Adhikary, S;Rauniyar, B;Pokharel, PK 3447

https://doi.org/10.14456/apjcp.2016.115/APJCP.2016.17.7.3447 KSCI

Background: Gall bladder cancer (GBC) is highly fatal disease with poor prognosis, with a 5 year survival rate of <10%. It is relatively rare cancer worldwide; however it is the sixth cancer and second most common gastrointestinal tract cancer in Nepalese women. The study focused on associations of certain demographic, lifestyle, dietary, and reproductive factors with gall bladder cancer. Materials and Methods: We conducted a hospital-based matched case control study on newly diagnosed cases of primary GBC at BP Koirala Institute of Health Sciences and BP Koirala Memorial Cancer Hospital. Controls were healthy non-GBC relatives of cancer patients, matched for age, sex and marital status (in case of females) with cases at a ratio of 1:2. Data were collected between April 2012-April 2013 by semi structured interview from both cases and controls. Analyses were carried out with SPSS. Conditional logistic regression was used to find odds ratios and 95% confidence intervals for bivariate and multivariate analysis. Results: A total of 50 cases and 100 controls were enrolled in this study. On bivariate analysis, factors found to be significantly associated with gallbladder cancer were illiteracy (OR=3.29, CI=1.06-10.2), history of gallstone disease (OR=27.6, CI=6.57, 115.6), current smoker (OR=2.42, CI=1.005-5.86), early menarche <13 years (OR=2.64, CI=1.09-6.44), high parity more than 3 (OR=3.12, CI=1.25,7.72), and use of mustard oil (OR=3.63, CI=1.40, 9.40). A significant protective effect was seen with high consumption of fruits at least once a week (OR=0.101, CI=0.03-0.35). On multivariate analysis, history of gallstone disease, early menarche, current smoker and high consumption of fruits persisted as significant factors. Conclusions: History of gallstone disease, cigarette smoking and early menarche were associated with increased risk of gallbladder cancer while high consumption of fruits was found to have a protective effect.

Pruksakorn, Dumnoensun;Phanphaisarn, Areerak;Pongnikorn, Donsuk;Daoprasert, Karnchana;Teeyakasem, Pimpisa;Chaiyawat, Parunya;Katruang, Narisara;Settakorn, Jongkolnee 3455

https://doi.org/10.14456/apjcp.2016.116/APJCP.2016.17.7.3455 KSCI

Osteosarcoma is a common primary malignant bone tumor in children and adolescents. Recent worldwide average incidences of osteosarcoma in people aged 0 to 24 years were 4.3 and 3.4 per million, respectively, with a ratio of 1.4:1. However, data on the incidence of osteosarcoma in Thailand are limited. This study analyzed the incidence of osteosarcoma in the upper northern region of Thailand, with a population of 5.85 million people (8.9% of the total Thai population), using data for the years 1998 to 2012, obtained from the Chiang Mai Cancer Registry (CMCR) at Chiang Mai University Hospital and the Lampang Cancer Registry (LCR) at the Lampang Cancer Hospital, a total of 144 cases. The overall annual incidence of osteosarcoma was 1.67 per million with a male:female ratio of 1.36:1. Incidences by age group (male and female) at 0 to 24, 25 to 59 and over 60 years were 3.5 (3.9 and 3.0), 0.8 (0.9 and 0.6), and 0.7 (0.8 and 0.5), respectively. The peak incidence occurred at 15 to 19 years for males and at 10 to 14 years for females. The median survival time was 18 months with a 5-year survival rate of 43%. Neither the age group nor the 5-year interval period of treatment was significantly correlated with survival during the 15-year period studied.

Ley, P;Yip, CH;Hong, C;Varughese, J;Camp, L;Bouy, Sok;Maling, E 3459

https://doi.org/10.14456/apjcp.2016.117/APJCP.2016.17.7.3459 KSCI

Background: Breast cancer is the second most common cancer in women in Cambodia, a low income country in South-East Asia. The Sihanouk Hospital Centre of Hope (SHCH) is a charity hospital set up by an international non-governmental organisation, HOPE Worldwide. In 2008, SHCH partnered with AmeriCares, a global health organisation to set up and deliver a breast cancer programme to provide education, diagnosis and treatment for women with breast cancer. The objective of this study is to characterise the presentation, diagnosis, treatment and outcomes of women treated under this program. Materials and Methods: A total of 215 women newly diagnosed with breast cancer from 1 March 2008 until 31 March 2011 were studied. Age at diagnosis, tumour size, histological type, tumour grade, ER, lymph node involvement, treatment modalities (surgery, radiotherapy, chemotherapy, hormone therapy) were recorded. Data on mortality at 3 years were obtained whenever possible. Results: The median age was 47 years old. Some 77.8% were diagnosed with stage 3 and 4 lesions, and 78.5% underwent mastectomy, of which 28.4% the intent was palliative. Of those whose ER status were known, only 48.3% were ER positive. Only 6 patients could afford chemotherapy while only 1 patient had radiotherapy. Hormone therapy was provided free for those who were ER positive. The overall survival rate at 3 years was 39.1%. Conclusions: Breast cancer presents at a late stage, and because treatment is suboptimal, survival is poor in Cambodia. A more aggressive approach to early detection and treatment needs to be developed to improve outcome from this potentially curable disease.

uz Zaman, Maseeh;Fatima, Nosheen;Zaman, Areeba;Zaman, Unaiza;Tahseen, Rabia 3465

https://doi.org/10.14456/apjcp.2016.118/APJCP.2016.17.7.3465 KSCI

Background: Fluorodeoxyglucose ($^{18}FDG$) PET/CT imaging has become an important component of the management paradigm in oncology. However, the significant imparted radiation exposure is a matter of growing concern especially in younger populations who have better odds of survival. The aim of this study was to estimate the effective dose received by patients having whole body $^{18}F$-FDG PET/CT scanning as per recent dose reducing guidelines at a tertiary care hospital. Materials and Methods: This prospective study covered 63 patients with different cancers who were referred for PET/CT study for various indications. Patients were prepared as per departmental protocol and 18FDG was injected at 3 MBq/Kg and a low dose, non-enhanced CT protocol (LD-NECT) was used. Diagnostic CT studies of specific regions were subsequently performed if required. Effective dose imparted by 18FDG (internal exposure) was calculated by using multiplying injected dose in MBq with coefficient $1.9{\times}10^{-2}mSv/MBq$ according to ICRP publication 106. Effective dose imparted by CT was calculated by multiplying DLP (mGy.cm) with ICRP conversion coefficient "k" 0.015 [mSv / (mG. cm)]. Results: Mean age of patients was $49{\pm}18$ years with a male to female ratio of 35:28 (56%:44%). Median dose of 18FDG given was 194 MBq (range: 139-293). Median CTDIvol was 3.25 (2.4-6.2) and median DLP was 334.95 (246.70 - 576.70). Estimated median effective dose imparted by $^{18}FDG$ was 3.69 mSv (range: 2.85-5.57). Similarly the estimated median effective dose by low dose (non-diagnostic) CT examination was 4.93 mSv (range: 2.14 -10.49). Median total effective dose by whole body 18FDG PET plus low dose non-diagnostic CT study was 8.85 mSv (range: 5.56-13.00). Conclusions: We conclude that the median effective dose from a whole body 18FDG PET/CT in our patients was significantly low. We suggest adhering to recently published dose reducing strategies, use of ToF scanner with CT dose reducing option to achieve the lower if not the lowest effective dose. This would certainly reduce the risk of second primary malignancy in younger patients with higher odds of cure from first primary cancer.

Liu, Lee 3469

https://doi.org/10.14456/apjcp.2016.119/APJCP.2016.17.7.3469 KSCI

Background: The cancer research literature suggests that women, especially premenopausal women, have lower cancer mortality rates than men. However, it is unclear if that is true for populations at all age levels in all countries and what factors affect such sex differences. This paper attempts to fill that gap. Materials and Methods: Sex- and country-specific cancer mortality data were statistically analyzed with particular attention to geographic, social, and economic factors that may affect the sex differences. Results: The sex differences were age and country specific, rather than universal. Premenopausal women actually tend to have a disadvantage compared to men or postmenopausal women. Male cancer mortality appears to be the affecting factor in explaining variations in sex differences. Latitude of residence and literacy rate are the affecting factors in cancer mortality and sex differences. African and Latin American countries tend to have a female disadvantage, while East Asian and Eastern European countries are more likely to have a female advantage. Conclusions: The findings challenge the cancer mortality literature and indicate that the sex differences and their possible causes are more complicated than the current literature suggests. They also highlight the urgency of adapting age- and country- specific health systems and policies to better meet the needs of younger women.

Gallegos-Vargas, JA;Sanchez-Roldan, J;Ronquillo-Sanchez, MD;Carmona-Aparicio, L;Floriano-Sanchez, E;Cardenas-Rodriguez, N 3477

https://doi.org/10.14456/apjcp.2016.120/APJCP.2016.17.7.3477 KSCI

Background: Thyroid cancer is the most common endocrine malignancy, and exact causes remain unknown. The role of CYP450 1A1 (CYP1A1) in cancer initiation and progression has been investigated. The aim of this work was to analyze, for the first time, CYP1A1 gene expression and its relationship with several clinicopathological factors in Mexican patients diagnosed with thyroid cancer. Materials and Methods: Real-time PCR analysis was conducted on 32 sets of thyroid tumors and benign pathologies. Expression levels were tested for correlations with clinical and pathological data. All statistical analysis were performed using GraphPad Prism version 3.0 software. Results: We found that female gender was associated with thyroid cancer risk (P<0.05). A positive relationship was identified between CYP1A1 mRNA levels and the presence of chronic disease, alcohol use, tumor size, metastasis and an advanced clinical stage (P<0.05). Conclusions: The results suggest that CYP1A1 gene expression could be used as a marker for thyroid cancer.

Baig, Mukhtiar;Bakarman, Marwan A;Gazzaz, Zohair J;Khabaz, Mohamad N;Ahmed, Tahir J;Qureshi, Imtiaz A;Hussain, Muhammad B;Alzahrani, Ali H;Al-Shehri, Ali A;Basendwah, Mohammad A;Altherwi, Fahd B;Al-Shehri, Fahd M 3483

https://doi.org/10.14456/apjcp.2016.121/APJCP.2016.17.7.3483 KSCI

Background: Cigarette smoking is one of the leading causes of death in the world. Tobacco consumption has grave negative consequences for health so that it is important to understand the reasons and motivations towards cigarette smoking and barriers against quitting smoking among the young generation for developing effective policies to control this widespread problem. Materials and Methods: This cross-sectional survey was carried out at the Faculty of Medicine, Rabigh, King Abdulaziz University, Jeddah, Saudi Arabia. A total of 438 young smokers participated from the University and the general population. Data were collected through anonymous, self-administered questionnaires in the Arabic language that contained questions about the reasons and motivations towards cigarette smoking and barriers against quitting smoking. The questionnaire also contained several questions regarding knowledge and attitude of the participants towards cigarette smoking. The data was analyzed on SPSS-16. Results: The mean age of the respondents was $22.9{\pm}3.48$, out of 438 subjects 87 (19.9%) were married, and 351 (80.1%) were unmarried, and 331 (75.6%) belonged to urban areas while 107 (24.5%) were from the rural areas. Responding to a question about a number of cigarettes smoked per day, 31% answered 11-20, 29% answered 21-30, and 25% answered 1-10. Questioned about smokers in the family, 34.5% responded more than one, with 19% for brother and 13% for father. About the reasons for not quitting smoking, 26% described lack of willpower, 25% had no reason, 22% said that people around me smoke, and 15.3% responded stress at home/work. The major motivation for smokers was smoker friends (42%), for 33.8% others, for 12% father/brother and 7.8% media. Conclusions: There are several avoidable and preventable reasons and barriers against quitting smoking. However, knowledge and attitude about smoking were good, and the majority of the smokers were well aware of the associated hazards. Therefore, there is a need to search out ways and means to help them to quit this addiction.

Othman, Nor Hayati;Zaki, Fatma Hariati Mohamad;Hussain, Nik Hazlina Nik;Yusoff, Wan Zahanim Wan;Ismail, Pazuddin 3489

https://doi.org/10.14456/apjcp.2016.122/APJCP.2016.17.7.3489 KSCI

Background: A major problem with cervical cancer screening in countries which have no organized national screening program for cervical cancer is sub-optimal participation. Implementation of self-sampling method may increase the coverage. Objective: We determined the agreement of cytological diagnoses made on samples collected by women themselves (self-sampling) versus samples collected by physicians (Physician sampling). Materials and Methods: We invited women volunteers to undergo two procedures; cervical self-sampling using the Evalyn brush and physician sampling using a Cervex brush. The women were shown a video presentation on how to take their own cervical samples before the procedure. The samples taken by physicians were taken as per routine testing (Gold Standard). All samples were subjected to Thin Prep monolayer smears. The diagnoses made were according to the Bethesda classification. The results from these two sampling methods were analysed and compared. Results: A total of 367 women were recruited into the study, ranging from 22 to 65 years age. There was a significant good agreement of the cytological diagnoses made on the samples from the two sampling methods with the Kappa value of 0.568 (p=0.040). Using the cytological smears taken by physicians as the gold standard, the sensitivity of self-sampling was 71.9% (95% CI:70.9-72.8), the specificity was 86.6% (95% CI:85.7-87.5), the positive predictive value was 74.2% (95% CI:73.3-75.1) and the negative predictive value was 85.1% (95% CI: 84.2-86.0). Self-sampling smears (22.9%) allowed detection of micro-organisms better than physicians samples (18.5%). Conclusions: This study shows that samples taken by women themselves (self-sampling) and physicians have good diagnostic agreement. Self-sampling could be the method of choice in countries in which the coverage of women attending clinics for screening for cervical cancer is poor.

Ikoma, Toshikazu;Kapoor, Vinay Kumar;Behari, Anu;Mishra, Kumudesh;Tsuchiya, Yasuo;Asai, Takao;Endoh, Kazuo;Okano, Kiyoshi;Nakamura, Kazutoshi 3499

https://doi.org/10.14456/apjcp.2016.124/APJCP.2016.17.7.3499 KSCI

Our recent studies conducted in South America have shown that mycotoxin contamination of red chili peppers (RCPs) may be associated with an increased risk of gallbladder cancer (GBC). Whether this relationship exists in India, a country with a high incidence of GBC and high consumption of RCPs, is unclear. We therefore measured concentrations of aflatoxins (AFs) and ochratoxin A (OTA) in RCPs from areas of low, medium, and high incidence of GBC in India, and compared these concentrations with GBC incidence in each area. Twenty-one RCP samples were collected from nine cities (eight from a low-incidence area, five from a medium-incidence area, and eight from a high-incidence area). Concentrations of AFs and OTA were measured using high-performance liquid chromatography. No significant differences in mean concentrations of AFs and OTA were found in the three areas. AFB1 levels in the low-incidence area ($10.81{\mu}g/kg$) and high-incidence area ($12.00{\mu}g/kg$) were more than 2.2 and 2.4 times higher compared with the maximum permitted level of AFB1 in spices ($5.0{\mu}g/kg$) set by the Commission of the European Communities, or that ($4.4{\mu}g/kg$) obtained in our previous study in Chile. Our results show that the mean concentrations of mycotoxins in RCPs are similar among the three areas in India with different incidences of GBC. Further studies with human subjects are needed to evaluate any association between AFB1 and GBC.

Wichachai, Suparp;Songserm, Nopparat;Akakul, Theerawut;Kuasiri, Chanapong 3505

https://doi.org/10.14456/apjcp.2016.125/APJCP.2016.17.7.3505 KSCI

Cervical cancer is a major public health problem in Thailand, being ranked second only to breast cancer. Thai women have been reported to have a low rate of cervical cancer screening (27.7% of the 80% goal of WHO). We therefore aimed to apply the social marketing theory and health belief model in promoting cervical cancer screening in Kanthararom District, Sisaket Province. A total of 92 from 974 targeted women aged 30-60 years were randomly divided into two groups. The experimental group underwent application of social marketing theory and a health belief model program promoting cervical cancer screening while the control group received normal services. Two research tools were used: (1) application of social marketing theory and health belief model program and (2) questionnaire used to evaluate perceptions of cervical cancer. Descriptive and inferential statistics including paired sample t-test and independent t-test were used to analyze the data. After the program had been used, the mean score of perception of cervical cancer of experimental group was at a higher level (${\bar{x}}=4.09$; S.D.=0.30), than in the control group (${\bar{x}}=3.82$; S.D.=0.20) with statistical significance (p<0.001). This research demonstrated an appropriate communication process in behavioral modification to prevent cervical cancer. It can be recommended that this program featuring social marketing and the health belief model be used to promote cervical cancer screening in targeted women and it can be promoted as a guideline for other health services, especially in health promotion and disease prevention.

Supaadirek, Chunsri;Pesee, Montien;Thamronganantasakul, Komsan;Thalangsri, Pimsiree;Krusun, Srichai;Supakalin, Narudom 3511

https://doi.org/10.14456/apjcp.2016.126/APJCP.2016.17.7.3511 KSCI

Purpose: To evaluate the treatment outcomes of patients with locally advanced rectal cancer treated with preoperative concurrent chemoradiotherapy (CCRT) or combined chemotherapy together with radiotherapy (CMT-RT) without surgery. Materials and Methods: A total of 84 patients with locally advanced rectal adenocarcinoma (stage II or III) between January $1^{st}$, 2003 and December $31^{st}$, 2013 were enrolled, 48 treated with preoperative CCRT (Gr.I) and 36 with combined chemotherapy and radiotherapy (CMT-RT) without surgery (Gr.II). The chemotherapeutic agents used concurrent with radiotherapy were either 5-fluorouracil short infusion plus leucovorin and/or capecitabine or 5-fluorouracil infusion alone. All patients received pelvic irradiation. Results: There were 5 patients (10.4%) with a complete pathological response. The 3 year-overall survival rates were 83.2% in Gr.I and 24.8 % in Gr.II (p<0.01). The respective 5 year-overall survival rates were 70.3% and 0% (p<0.01). The 5 year-overall survival rates in Gr.I for patients who received surgery within 56 days after complete CCRT as compared to more than 56 days were 69.5% and 65.1% (p=0.91). Preoperative CCRT used for 12 of 30 patients in Gr.I (40%) with lower rectal cancer demonstrated that in preoperative CCRT a sphincter sparing procedure can be performed. Conclusions: The results of treatment with preoperative CCRT for locally advanced rectal cancer showed comparable rates of overall survival and sphincter sparing procedures as compared to previous studies.

Wongmeerit, Phunnipit;Suwanrungruang, Krittika;Jetsrisuparb, Arunee;Komvilaisak, Patcharee;Wiangnon, Surapon 3515

https://doi.org/10.14456/apjcp.2016.127/APJCP.2016.17.7.3515 KSCI

Background: In Thailand, a national treatment protocol for childhood leukemia and lymphoma (LL) was implemented in 2006. Access to treatment has also improved with the National Health Security system. Since these innovations, survival of childhood LL has not been fully described. Materials and Methods: Trends and survival of children under 15 with childhood cancers diagnosed between 1993 and 2012 were investigated using the hospital-based data from the Khon Kaen Cancer Registry, Srinagarind Hospital, Faculty of Medicine, Khon Kaen University, Thailand. Childhood cancers were classified into 12 diagnostic groups, according to the ICCC based on the histology of the cancer. Survival rates were described by period, depending on the treatment protocol. For leukemias and lymphomas, survival was assessed for 3 periods (1993-99, 2000-5, 2006-12) while for solid tumors it was for 2 periods (before and after 2000). The impacts of sex, age, use of the national protocol, and catchment area on leukemia and lymphoma were evaluated. Overall survival was calculated using the Kaplan-Meier method while the Cox proportional hazard model was used for multivariate analysis. Trends were calculated using the R program. Results: A total of 2,343 childhood cancer cases were included. Survival for acute lymphoblastic leukemia (ALL) from 1993-9, 2000-5, and 2006-12 improved significantly (43.7%, 64.6%, and 69.9%). This was to a lesser extent true for acute non-lymphoblastic leukemia (ANLL) (28.1%, 42.0%, and 42.2%). Survival of non-Hodgkin lymphoma (NHL) also improved significantly (44%, 65.5%, and 86.8%) but not for Hodgkin disease (HD) (30.1%, 66.1%, and 70.6%). According to multivariate analysis, significant risk factors associated with poor survival in the ALL group were age under 1 and over 10 years, while not using the national protocol had hazard ratios (HR) of 1.6, 1.3, and 2.3 respectively. In NHL, only non-use of national protocols was a risk factor (HR 3.9). In ANLL and HD, none of the factors influenced survival. Survival of solid tumors (liver tumors, retinoblastomas) were significantly increased compared to after and before 2000 while survival for CNS tumors, neuroblastoma and bone tumors was not changed. Conclusions: The survival of childhood cancer in Thailand has markedly improved. Since implementation of national protocols, this is particularly the case for ALL and NHL. These results may be generalizable for the whole country.

Agostino, Pozzi;Angelo, Della Corte;el Lakis, Mustapha A;Heon-Jae, Jeong 3521

https://doi.org/10.14456/apjcp.2016.128/APJCP.2016.17.7.3521 KSCI

Digital breast tomosynthesis (DBT) as a breast cancer screening modality, through generation of three-dimensional images during standard mammographic compression, can reduce interference from breast tissue overlap, increasing conspicuity of invasive cancers while concomitantly reducing false-positive results. We here conducted a systematic review on previous studies to synthesize the evidence of DBT efficacy, eventually 18 articles being included in the analysis. The most commonly emerging topics were advantages of DBT screening tool in terms of recall rates, cancer detection rates and cost-effectiveness, preventing unnecessary burdens on women and the healthcare system. Further research is needed to evaluate the potential impact of DBT on longer-term outcomes, such as interval cancer rates and mortality, to better understand the broader clinical and economic implications of its adoption.

Zaid, Khaled Waleed;Nhar, Bander Mossa;Alanazi, Salman Mohammed Ghadeer;Murad, Rashad;Domani, Ahmad;Alhaf, Awadh Jamman 3527

https://doi.org/10.14456/apjcp.2016.129/APJCP.2016.17.7.3527 KSCI

Recombinant human bone morphogenetic protein-2 (rhBMP-2 ), a member of the TGF-${\beta}$ family, has been used widely in recent years to regenerate defects of the maxillary and mandible bones. Such defects are sometimes caused by resection of oral squamous cell carcinoma (OSCC) yet the biologic effects of rhBMP-2 on these carcinomas are not fully clear. The objective of this study was to determine histologically whether rhBMP-2 produces adverse effects on angiogenesis during induction of OSCC, a biologic process critical for tumor formation in an experimental model in the buccal pouch of golden Syrian hamsters. Buccal cavities were exposed to painting with 0.5% DMBA in liquid paraffin three times a week for 14 weeks, then biopsies were taken. Division was into 2 groups: a study group of 10 hamsters receiving $0.25{\mu}g/ml$ of rhBMP-2 in the $3^{rd}$ and $6^{th}$ weeks; and a control group of 10 hamsters which did not receive any additional treatment. VEGF expression and microvessel density were measured but no differences were noted between the two groups. According to this study, rh-BMP-2 does not stimulate angiogenesis during induction of OCSSs.

Talip, Tajidah;Kifli, Nurolaini;Murang, Zaidah;Naing, Lin 3533

https://doi.org/10.14456/apjcp.2016.130/APJCP.2016.17.7.3533 KSCI

Background: Cigarette smoking is one of the leading global causes of premature and preventable death. In Brunei Darussalam, smoking-related diseases have been a primary cause of mortality for the past three decades. Despite the increasing efforts that have been made in recent years to reduce the consumption of tobacco products in Brunei, the prevalence of adolescent smoking cigarette, however has risen alarmingly, from 8.9% in 2013 to 11.4% in 2014, with a higher prevalence found in males (17.8%) than in females (4.8%). In response to the need for more effective smoking prevention programmes in Brunei, this study sought to explore factors that influence Bruneian male adolescents to start and continue smoking. Materials and Methods: A qualitative study using focus group discussions (FGDs) as the data collection method was conducted from October to November 2015. A total of 43 studentss, comprising 31 smokers and 12 non-smokers, aged 13-17 years, from two government secondary schools in Bandar Seri Begawan, participated in six FGDs. Discussions were recorded and translated. Transcripts were entered into NVivo10, before thematic analysis was conducted. Results: We identified three themes under the core construct of 'factors influencing smoking initiation' ('family as teachers', 'overt pressure from peers' and 'perceived smoking has many advantages') and three themes under the core construct of 'factors influencing smoking continuation' ('craving and addiction', 'smoking as a 'social activity' and 'easy accessibility of cigarettes'). Conclusions: Based on the findings, it is recommended that future prevention activities should be embedded in a comprehensive approach, involving all stakeholders within a community, and should be focused towards bringing a change in smoking and parenting behavior of parents, social norms within the culture towards all population levels, and at strengthening the existing non-smoking policies in schools and other public places where young people congregate.

Sungwalee, Waraporn;Vatanasapt, Patravoot;Suwanrungruang, Krittika;Promthet, Supannee 3541

https://doi.org/10.14456/apjcp.2016.131/APJCP.2016.17.7.3541 KSCI

Background: As the treatment modalities for oral cancer have been relatively consistent during the last two-decades, this study was conducted to compare survivals of oral cancer patients in Khon Kaen Province before and after the universal coverage scheme (UC) was launched in Thailand. Materials and Methods: The data were retrieved from the population-based cancer registry of Khon Kaen for oral cancer patients diagnosed during 1992-2001 (pre-UC), and 2004-2012 (post-UC). To compare survival of the two cohorts, Kaplan Meier and log rank tests were employed. Results: Of 1,196 patients, 65% were females and the median age was 65 years. The most common primary sites were lip (31.0%), tongue (29.9%), and buccal mucosa (14.6%). The proportion of early stage cancer increased from 20.4 % in pre-UC to 41.3% in post-UC. The overall 5-year survival rate was 36.5% (95% CI =32.6-40.9) for pre-UC and 32.4% (95% CI = 28.8-36.4) for post-UC. The declining survival was mainly due to an increasing proportion of tongue cancer. However, no survival improvement was demonstrated on subgroup analysis of the tongue cancer patients. Conclusions: After the universal coverage scheme had been launched, early diagnosis increased, but no significant gain in survival for oral cancer patients was achieved.

Washio, Masakazu;Mori, Mitsuru;Mikami, Kazuya;Miki, Tsuneharu;Watanabe, Yoshiyuki;Nakao, Masahiro;Kubo, Tatsuhiko;Suzuki, Koji;Ozasa, Kotaro;Wakai, Kenji;Tamakoshi, Akiko 3545

https://doi.org/10.14456/apjcp.2016.132/APJCP.2016.17.7.3545 KSCI

Background: The incidence of bladder cancer is lower in Asian than in Western countries. However, the crude incidence and mortality of bladder cancer have recently increased in Japan because of the increased number of senior citizens. We have already reported risk factors for urothelial cancer in a large population-based cohort study in Japan (JACC study). However, we did not evaluate the cancer risk in the upper and lower urinary tract separately in our previous study. Materials and Methods: Here we evaluated the risk of cancer death in the upper and lower urinary tracts, separately, using the database of the JACC study. The analytic cohort included 46,395 males and 64,190 females aged 40 to 79 years old. The Cox proportional hazard model was used to determine hazard ratios and their 95% confidence intervals. Results: Current smoking increased the risk of both upper and lower urinary tract cancer deaths. A history of kidney disease was associated with an increased risk of bladder cancer death, even after controlling for age, sex and smoking status. Conclusions: The present study confirmed that current smoking increases the risk of both upper and lower urinary tract cancer deaths and indicated the possibility that a history of kidney disease may be a risk factor for bladder cancer death in the Japanese population.

Reungpatthanaphong, Sareeya;Chaiyasut, Chaiyavat;Sirilun, Sasithorn;Suwannalert, Prasit 3551

https://doi.org/10.14456/apjcp.2016.133/APJCP.2016.17.7.3551 KSCI

Colorectal cancer (CRC) is a major cause of morbidity and mortality throughout the world, with chronic inflammation and diet as major causes in its development. Chemopreventive effects of natural dietary products have been the focus of studies for prevention over the past decade. This study was conducted to determine the effects of unpolished Thai rice during precancerous stage through the involvement of ${\beta}$-catenin, cyclooxygenase-2 (COX-2) expression and inflammatory cytokines focusing on azoxymethane (AOM)-induced aberrant crypt foci (ACF)-related to CRC. Male Sprague Dawley rats received two injections of AOM (15 mg/kg body weight) at weeks 4 and 5 while rats were treated with 20% or 70% unpolished Thai rice. The rats were sacrificed at week 38 and the colons removed for aberrant crypt foci (ACF) identification. Histopathologic changes, immunohistochemical analysis of ${\beta}$-catenin and COX-2 expression, and cytokine expression of proinflammatory and anti-inflammatory markers were determined. The administration of unpolished Thai rice significantly and dose dependently decreased the total number of ACF and the percentages of ACF with high-grade dysplasia. Interestingly, unpolished Thai rice suppressed the expression of ${\beta}$-catenin and COX-2. In addition, it also altered proinflammatory (IL-6 and IFN-${\gamma}$) and anti-inflammatory (IL- 10) markers. The results suggested that unpolished Thai rice may provide a promising dietary intake for prevention during precancerous stage of CRC development, through the involvement of ${\beta}$-catenin and COX-2 expression, and also modulate inflammatory cytokines-related to CRC.

Diab, Kawthar AE 3559

https://doi.org/10.14456/apjcp.2016.134/APJCP.2016.17.7.3559 KSCI

Background: In recent years, there has been considerable research on recycling of agro-industrial waste for production of bioactive compounds. The food processing industry produces large amounts of citrus peels that may be an inexpensive source of useful agents. Objective: The present work aimed to explore the phytochemical content, antioxidant, anticancer, antiproliferation, and antigenotxic activities of lemon, grapefruit, and mandarin peels. Materials and Methods: Peels were extracted using 98% ethanol and the three crude extracts were assessed for their total polyphenol content (TPC), total flavonoid content (TFC), and antioxidant activity using DPPH (1, 1-diphenyl-2-picrylhydrazyl). Their cytotoxic and mitogenic proliferation activities were also studied in human leukemia HL-60 cells and mouse splenocytes by CCK-8 assay. In addition, genotoxic/antigenotoxic activity was explored in mouse splenocytes using chromosomal aberrations (CAs) assay. Results: Lemon peels had the highest of TPC followed by grapefruit and mandarin. In contrast, mandarin peels contained the highest of TFC followed by lemon and grapefruit peels. Among the extracts, lemon peel possessed the strongest antioxidant activity as indicated by the highest DPPH radical scavenging, the lowest effective concentration 50% ($EC_{50}=42.97{\mu}g\;extract/mL$), and the highest Trolox equivalent antioxidant capacity (TEAC=0.157). Mandarin peel exhibited moderate cytotoxic activity ($IC_{50}=77.8{\mu}g/mL$) against HL-60 cells, whereas grapefruit and lemon peels were ineffective anti-leukemia. Further, citrus peels possessed immunostimulation activity via augmentation of proliferation of mouse splenocytes (T-lymphocytes). Citrus extracts exerted non-cytotoxic, and antigenotoxic activities through remarkable reduction of CAs induced by cisplatin in mouse splenocytes for 24 h. Conclusions: The phytochemical constituents of the citrus peels may exert biological activities including anticancer, immunostimulation and antigenotoxic potential.

Chotipanich, Chanisa;Kunawudhi, Anchisa;Promteangtrong, Chetsadaporn;Tungsuppawattanakit, Puntira;Sricharunrat, Thaniya;Wongsa, Paramest 3569

https://doi.org/10.14456/apjcp.2016.135/APJCP.2016.17.7.3569 KSCI

Purpose: The aim of this study was to compare C-11 choline and F-18 FDG PET/CT, gadoxetic-enhanced 3-T MRI and contrast-enhanced CT for diagnosis of hepatocellular carcinoma (HCC). Materials and Methods: Twelve chronic hepatitis B patients suspected of having HCC by abdominal ultrasonography received all diagnostic modalities performed within a one-week timeslot. PET/CT results were analyzed visually by two independent nuclear medicine physicians and quantitatively by tumor to background ratio (T/B). Nine patients then had histopathological confirmation. Results: Six patients had well differentiated HCC, while two and one patient(s) were noted with moderately and poorly differentiated HCC, respectively. All were detected by both CT and MRI with an average tumor size of $5.7{\pm}3.8cm$. Five patients had positive C-11 choline and F-18 FDG uptake. Of the remaining four patients, three with well differentiated HCC showed negative F-FDG uptake (one of which showed negative results by both tracers) and one patient with moderately differentiated HCC demonstrated no C-11 choline uptake despite intense F-18 FDG avidity. The overall HCC detection rates with C-11 choline and F-18 FDG were 78% and 67%, respectively, while the sensitivity of F-18 FDG for non-well differentiated HCC was 100%, compared with 83% of C-11 choline. The average T/B of C-11 choline in well-differentiated HCC patients was higher than in moderately and poorly differentiated cases (p=0.5) and vice versa with statistical significance for T/B of F-18 FDG (p = 0.02). Conclusions: Our results suggested better detection rate in C-11 choline for well differentiated HCC than F-18 FDG PET. However, the overall detection rate of PET/CT with both tracers could not compare with contrast-enhanced CT and MRI.

Hassan, Muhammad Radzi Abu;Suan, Mohd Azri Mohd;Soelar, Shahrul Aiman;Mohammed, Noor Syahireen;Ismail, Ibtisam;Ahmad, Faizah 3575

https://doi.org/10.14456/apjcp.2016.136/APJCP.2016.17.7.3575 KSCI

Background: Cancer survival analysis is an essential indicator for effective early detection and improvements in cancer treatment. This study was undertaken to document colorectal cancer survival and associated prognostic factors in Malaysians. Materials and Methods: All data were retrieved from the National Cancer Patient Registry-Colorectal Cancer. Only cases with confirmed diagnosis through histology between the year 2008 and 2009 were included. Retrieved data include socio-demographic information, pathological features and treatment received. Survival curves were plotted using the Kaplan-Meier method. Univariate analysis of all variables was then made using the Log-rank test. All significant factors that influenced survival of patients were further analysed in a multivariate analysis using Cox' regression. Results: Total of 1,214 patients were included in the study. The overall 3- and 5-year survival rates were 59.1% and 48.7%, respectively. Patients with localized tumours had better prognosis compared to those with advanced stage cancer. In univariate analysis, staging at diagnosis (p<0.001), primary tumour size (p<0.001), involvement of lymph nodes (p<0.001) and treatment modalities (p=0.001) were found to be predictors of survival. None of the socio-demographic characteristics were found to exert any influence. In Cox regression analysis, staging at diagnosis (p<0.001), primary tumour size (p<0.001), involvement of lymph nodes (p<0.001) and treatment modalities (p<0.001) were determined as independent prognostic factors of survival after adjusted for age, gender and ethnicity. Conclusions: The overall survival rate for colorectal cancer patients in Malaysia is similar to those in other Asian countries, with staging at diagnosis, primary tumor size, involvement of lymph node and treatment modalities having significant effects. More efforts are needed to improve national survival rates in future.

Shandiz, Fatemeh Homaee;Karimi, Fatemeh Zahra;Rahimi, Nafiseh;Abdolahi, Mahboubeh;Anbaran, Zahra Khosravi;Ghasemi, Mina;Mazlom, Seyed Reza;Kheirabadi, Aghileh Nasaghchi 3583

https://doi.org/10.14456/apjcp.2016.137/APJCP.2016.17.7.3583 KSCI

Background: Since the breast is strongly relevant to sexual desire, and physical and sexual attractiveness, the high prevalence of breast cancer (BC) in Iran and long-term survival of patients experiencing side effects means that measures to identify associated sexual problems are necessary. Therefore, this study was conducted to assess sexual function and affecting factors in women with BC. Materials and Methods: This cross-sectional study was performed on 94 women with BC, referred to Imam Reza (AS) Hospital, Mashhad, Iran, in 2014. The data were collected through demographic and clinical questionnaires and also a sexual function questionnaire and analyzed using SPSS version 16. Results: The total score of women's sexual function was about $24.3{\pm}4.41$. Of the total, 63 (71.3%) reported sexual dysfunction, for example reduced satisfaction or more pain. Age was the only significantly related factor. Conclusions: Breast cancer can adversely affect women's sexual function and decrease quality of life. Thus, taking measures to overcome women's sexual problems are necessary.

Borghesan, Deise Helena Pelloso;Dell'Agnolo, Catia Millene;Gravena, Angela Andreia Francam;de Oliveira Demitto, Marcela;Lopes, Tiara Cristina Romeiro;de Barros Carvalho, Maria Dalva;Pelloso, Sandra Marisa 3587

https://doi.org/10.14456/apjcp.2016.138/APJCP.2016.17.7.3587 KSCI

Purpose: To analyze risk factors for postmenopausal breast cancer. Methods: The present case-control study included 600 women treated at a cancer center reference hospital in a municipality in the South of Brazil. Results: Totals of 100 patients and 500 control subjects were evaluated. The mean age of the women was $52.5{\pm}11.9$ years; the average was $57.4{\pm}11.8$ years, and the average age of the control subjects was $51.5{\pm}11.7$ years. The risk factors for breast cancer that were considered included an age ${\geq}40$ years, postmenopausal status, a body mass index $(BMI){\geq}30kg/m^2$, and reduced physical activity. Variables like postmenopausal status and an obese BMI were associated with cases of breast cancer. Women who were postmenopausal or obese were 3.80 or 1.80 times more likely to develop breast cancer, respectively, and physically inactive women were 1.72 times more likely to develop breast cancer. Conclusions: Obesity and postmenopausal status are associated with the occurrence of breast cancer in this population. Being over 40 years of age was also a statistically significant factor for postmenopausal women.

Rasmy, A;Abozeed, W;Elsamany, S;El Baiomy, M;Nashwa, A;Amrallah, A;Hasaan, E;Alzahrani, A;Faris, M;Alsaleh, K;AlFaraj, A 3595

https://doi.org/10.14456/apjcp.2016.139/APJCP.2016.17.7.3595 KSCI

Background: To investigate the association between preoperative pathological Ki-67 labeling index and serum tumor marker cancer antigen 15-3 (CA 15-3) with clinic-pathological parameters and treatment outcomes in early breast cancer. Materials and Methods: A retrospective study at 4 cancer centers in Saudi Arabia and Egypt was performed. Data were collected for female patients diagnosed with unilateral early breast cancer between March 2010 and October 2013. Cases treated with neoadjuvant chemotherapy (NACT) followed by surgery and radiotherapy were included. NACT included 6-8 cycles of anthracycline and taxane based regimens. Trastuzumab and hormonal treatments were added according to HER2 and hormone receptor status. Baseline serum CA15.3 and pathological Ki67 levels were evaluated and correlated with disease free survival (DFS) and overall survival (OS). Results: A total of 280 pts was included. The median age was 49 years (38-66 y) and median overall survival was 35 (20-38) months (mo). Estrogen receptors (ER), progesterone receptors (PR) and HER 2 receptors were positive in 233 (83.2%), 198 (70%) and 65 cases (23.2%), respectively. High preoperative Ki67 and CA15.3 were noted in 177 (63.2%) and 131 (46.8%). A total of 45 (16%) patients had distal or local recurrence and 24 (8.6%) died of their disease. Most of the relapsed cases had high preoperative Ki-67 (n=41, 91%) and CA15.3 (n=28, 62%) values. All of the patients who died had a high Ki-67 but CA15.3 was high in 9 (37%) only. Mean DFS/OS in patients with high preoperative Ki-67 was 32 months /32 months as compared to 37 months/35 months in those with normal Ki-67 (p<0.001). Correlation of preoperative CA15.3 and survival was statistically not significant. Conclusions:Preoperative Ki-67 can be a predictive and prognostic marker. Higher levels are associated with poor DFS and OS in patients with early BC.

Mardani, Maryam;Andisheh-Tadbir, Azadeh;Khademi, Bijan;Melekzadeh, Mahyar;Vaziri, Lida 3601

https://doi.org/10.14456/apjcp.2016.140/APJCP.2016.17.7.3601 KSCI

Background: The monocyte chemoattractant protein-1 (MCP-1/CCL2) is a potent chemoattractant for natural killer cells, monocytes, and memory T lymphocytes. However, any role in the genesis of salivary gland tumors (SGT) is unknown. To assess the diagnostic relevance of chemokines in SGT, MCP-1 levels in the serum of patients were investigated in association with tumor progression and clinical aggressiveness. Materials and Methods: Using an ELISA kit, we assessed and compared the circulating levels of MCP-1 in blood serum of 70 SGT patients with 44 healthy control samples. Results: The results of this study showed that the concentration of MCP-1 was significantly lower in patients with benign ($463.8{\pm}158.5pg/ml$, P=0.033) and malignant ($454.8{\pm}190.4pg/ml$, P=0.007) SGT than in healthy subjects ($645.7{\pm}338.9$). No significant difference in mean serum levels of MCP-1 was observed between the benign and malignant group (p=0.9). While MCP-1 levels were lower in patients with an advanced clinical stage, advanced tumor size, higher tumor grade, or lymph node involvement, but the mean MCP-1 level between groups showed no statistically significant difference (p>0.05). Conclusions: MCP-1 levels in the serum of patients with SGT were decreased, indicating that this might a good marker for discriminating patients with SGT from healthy people. However, no clear-cut relationship was detected between MCP-1 levels and clinicopathologic factors, and MCP-1 is not a good marker for evaluating tumor dissemination.

Ahmadvand, Mohammad;Noruzinia, Mehrdad;Soleimani, Masoud;Abroun, Saeid 3605

https://doi.org/10.14456/apjcp.2016.141/APJCP.2016.17.7.3605 KSCI

Background: Histone acetylation in chromatin structures plays a key role in regulation of gene transcription and is strictly controlled by histone acetyltransferase (HAT) and deacetylase (HDAC) activities. HDAC deregulation has been reported in several cancers. Materials and Methods: The expression of 10 HDACs (including HDAC class I and II) was studied by quantitative reverse transcription-PCR (qRT-PCR) in a cohort of mesenchymal stem cells (MM-MSCs) from 10 multiple myeloma patients with a median age 60y. The results were compared with those obtained for normal donors. Then, a coculture system was performed between MM-MSCs and u266 cell line, in the presence or absence of sodium butyrate (NaBT), to understand the effects of HDAC inhibitors (HDACi) in MM-MSCs on multiple myeloma cases. Also, the interleukin-6 (IL-6) and vascular endothelial growth factor (VEGFA) gene expression level and apoptotic effects were investigated in MM-MSCs patients and control group following NaBT treatment. Results: The results indicated that upregulated (HDACs) and downregulated (IL6 and VEGFA) genes were differentially expressed in the MM-MSCs derived from patients with multiple myeloma and ND-MSCs from normal donors. Comparison of the MM-MSCs and ND-MSCs also showed distinct HDACs expression patterns. For the first time to our knowledge, a significant increase of apoptosis was observed in coculture with MM-MSCs treated with NaBT. Conclusions: The obtained findings elucidate a complex set of actions in MSCs in response to HDAC inhibitors, which may be responsible for anticancer effects. Also, the data support the idea that MSCs are new therapeutic targets as a potential effective strategy for MM.

Akhavan-Karbassi, Mohammad Hasan;Yazdi, Mohammad Forat;Ahadian, Hakimeh;Sadr-Abad, Maryam Jalili 3611

https://doi.org/10.14456/apjcp.2016.142/APJCP.2016.17.7.3611 KSCI

Background: Propolis based preparations have a wide range of applications in various specialties of dentistry. The aim of this clinical trial was to test the efficacy of propolis as a mouthwash in the reduction of chemotherapy induced oral mucositis (OM) in a single center. Materials and Methods: In this randomised, controlled study patients undergoing chemotherapy were included consecutively and randomised to an experimental group receiving propolis mouthwash (n = 20) and a control group receiving diluted water (n=20). Oral mucositis, erythema and eating and drink ability were assessed at baseline and after 3 and 7 days using the World Health Organization (WHO) scale and the oral mucositis assessment scale (OMAS). Results: There were significant differences in OM, wound and erythema in propolis group compared to placebo, but no significant difference in eating and drink ability. However, it was interesting that 65% of the patients in the propolis group were completely healed at day 7 of the trial. No significant adverse events were reported by the patients. Conclusions: This study found that oral care with propolis as mouthwash for patients undergoing chemotherapy is an effective intervention to improve oral health. Our findings shouldlencourage health practitioners to apply propolis mouth rinse for the oral care of patients under chemotherapy.

Miresmaeili, Sayed Mohsen;Tamandani, Dor Mohammad Kordi;Kalantar, Seyed Mehdi;Moshtaghiun, Seyed Mohammad 3615

https://doi.org/10.14456/apjcp.2016.143/APJCP.2016.17.7.3615 KSCI

Background: Breast cancer molecular analysis by linkage analysis has the advantage of facilitating early diagnosis in asymptomatic genetic carriers, with a view to the preventive follow-up of these subjects and genetic counseling. The aim of this study was to evaluate BRCA1 gene D17S855 and D17S1322 markers in breast cancer patients. Materials and Methods: A series of 85 BC patients and 85 unrelated healthy women were recruited for haplotype analysis performed using two short tandem repeat markers located within the BRCA1 gene locus. Each marker was amplified with PCR genomic DNA from each individual and fluorescently end-labeled primers. Results: Both D17S855 and D17S1322 markers included 12 kinds of alleles. Results indicate that most of the BC patients shared two common 121-150 (11.2%, RR=1.56 and p=0.02) and 121-146 (5.6%, RR=1.9 and p=0.02) haplotypes. Conclusions: Our results should be helpful to understand the haplotype phase in the BRCA1 gene and establish a genetic screening strategy in the Iranian population.

Zubair, Muhammad;Hashmi, Shoaib Naiyar;Afzal, Saeed;Muhammad, Iqbal;Din, Hafeez Ud;Ahmed, Rabia 3619

https://doi.org/10.14456/apjcp.2016.144/APJCP.2016.17.7.3619 KSCI

Background: Triple negative breast cancers (TNBCs) are high grade aggressive tumors generally with a poor prognosis, not responding to hormonal and anti Her2 Neu therapy. Expression of the antiapoptotic B cell lymphoma 2 gene (Bcl-2) is associated with low grade, slowly proliferating hormone receptor positive tumors with improved survival. Anti Bcl2 agents can be used as alternative targeted therapy in triple negative cancers. Materials and Methods: The objective of this study was to determine the immunohistochemical expression of Bcl2 in triple negative breast cancers and any correlation with clinicopathological variables in Northern Pakistan. Results: All 52 patients were females, aged between 28 and 80 years(average $48.0{\pm}12.1$). 28 cases (53.8%) were positive for Bcl2, this being associated with low grade invasive ductal carcinomas, lymph node metastasis and lymphovascular invasion. Conclusions: Bcl-2 may be an important prognostic factor and its expression might be used for targeted therapy using Anti Bcl2 drugs.

Baloch, Abdul Hameed;Khosa, Ahmad Nawaz;Bangulzai, Nasrullah;Shuja, Jamila;Naseeb, Hafiz Khush;Jan, Mohammad;Marghazani, Illahi Bakhsh;Kakar, Masood-ul-Haq;Baloch, Dost Mohammad;Cheema, Abdul Majeed;Ahmad, Jamil 3623

https://doi.org/10.14456/apjcp.2016.145/APJCP.2016.17.7.3623 KSCI

Breast cancer is very common and the leading cause of cancer deaths among women globally. Hereditary cases account for 5-10% of the total burden and CHEK2, which plays crucial role in response to DNA damage to promote cell cycle arrest and repair or induce apoptosis, is considered as a moderate penetrance breast cancer risk gene. Our objective in the current study was to analyze mutations in related to breast cancer. A total of 271 individuals including breast cancer patients and normal subjects were enrolled and all 14 exons of CHEK2 were amplified and sequenced. The majority of the patients (>95%) were affected with invasive ductal carcinoma (IDC), 52.1% were diagnosed with grade III tumors and 56.2% and 27.5% with advanced stages III and IV. Two novel nonsense variants i.e. c.58C>T (P.Q20X) and c.256G>T (p.E85X) at exon 1 and 2 in two breast cancer patients were identified, both novel and not reported elsewhere.

Govindarajan, Giri Valanthan Veda;Bhanumurthy, Lokesh;Balasubramanian, Anandh;Ramanathan, Arvind 3627

https://doi.org/10.14456/apjcp.2016.153/APJCP.2016.17.7.3627 KSCI

Background: Activation and inactivation of nuclear factor of kappa light chain gene enhancer in B cells (NFKB) is tightly regulated to ensure effective onset and cessation of defensive inflammatory signaling. However, mutations within NFKB, or change in activation and inactivation molecules have been reported in a few cancers. Although oral squamous cell carcinoma is one of the most prevalent forms of cancer in India, with a development associated with malignant transformation of precancerous lesions, the genetic status of NFKB and relative rates of change in oral precancerous lesions remain unknown. Hence in the present study we investigated all twenty four exons of NFKB gene in two precancerous lesions, namely oral submucous fibrosis (OSMF) and oral leukoplakia (OL) to understand its occurrence, incidence and assess its possible contribution to malignant transformation. Materials and Methods: Chromosomal DNA isolated from twenty five each of OSMF and OL tissue biopsy samples were subjected to PCR amplification with intronic primers flanking twenty four exons of the NFKB gene. The PCR amplicons were subsequently subjected to direct sequencing to elucidate the mutation status. Results: Sequence analysis identified a novel heterozygous mutation, c.419T>A causing substitution of leucine with glutamine at codon 140 (L140Q) in an OL sample. Conclusions: The identification of a substitution mutation L140Q within the DNA binding domain of NFKB in OL suggests that NFKB mutation may be relatively an early event during transformation. To the best of our knowledge, this study is the first to have identified a missense mutation in NFKB in OL.

Bano, Razia;Zafar, Waleed;Khan, Amina Iqbal;Fiaz, Sohaib Adil;Abid, Mahwish;Chaudhary, Mohammad Zulqarnain;Siddique, Neelam;Khan, Huma Majeed 3631

https://doi.org/10.14456/apjcp.2016.146/APJCP.2016.17.7.3631 KSCI

Background: Breast lymphomas constitute a rare disease entity. To date, limited relevant data have been reported. We therefore here present a review of breast lymphoma patients treated at a single center over a 20 year period, focusing on histological types, treatment modalities and outcomes. Materials and Methods: We identified patients who were diagnosed and treated for breast lymphoma at a single center from January 1995 to January 2014 and extracted data regarding patients' demographics and clinical data. Results: Twenty-seven patients with breast lymphoma were identified, of which 3 were males. The median age at diagnosis was 37 years (range: 22-76 years). Chemotherapy was the main stay of treatment and 55.6% patients also received radiation to the affected breast. At our institute, only 3 patients, all with progressive disease, had surgery performed to achieve local palliation. Complete response after chemotherapy was seen in 63% patients and partial response in 7.4%, while 26% patients demonstrated disease progression. The mean follow up was 46.8 months. Seven patients (33.3%) who were alive at last follow up, as well as 1 patient who died, survived more than 5 years after diagnosis. Conclusions: Patients with breast lymphoma should receive aggressive treatment, with combination of chemotherapy and radiation therapy. Surgery should be limited for diagnosis and palliation of local symptoms in cases of progressive disease.

de Abreu, Andre LP;Gimenes, Fabricia;Malaguti, Natalia;Pereira, Monalisa W;Uchimura, Nelson S;Consolaro, Marcia EL 3637

https://doi.org/10.14456/apjcp.2016.147/APJCP.2016.17.7.3637 KSCI

To determine the prevalence of human papillomavirus (HPV) among women with atypical squamous cells of undetermined significance (ASC-US) referred to colposcopy and the implications for clinical management in low- and middle-income countries (LMIC), the present study was conducted. We included 200 women living in $Maring{\acute{a}}$/Brazil referred to colposcopy service between August 2012 and March 2013 due to an abnormal cytology from ASC-US until high-grade intraepithelial lesion (HSIL). HPV was detected and genotyped by polymerase chain reaction (PCR). The mean age was $36.8{\pm}10.5$ years, and women with and without ASC-US had similar mean ages ($37.4{\pm}11.5$ and $36.4{\pm}9.96$ years, respectively). The highest prevalence of ASC-US occurred at 20-24 years (40%). HPV-DNA was positive in 164 (82.0%) women.Of the 57 women with ASC-US, 30 (52.6%) were HPV-DNA-positive and 21 (70%) were high-risk HPV-positive (HR-HPV); the latter was similar to women without ASC-US (76.9%) but with other abnormal cytological findings present. Our data demonstrated that performing tests for HR-HPV can be used for management of women with ASC-US to support the decision of which women should be referred for an immediate or later colposcopy. The same conclusions can be applied to other LMICs for which HPV testing for primary screening has not been adopted.

Belaid, A;Nasr, C;Benna, M;Cherif, A;Jmour, O;Bouguila, H;Benna, F 3643

https://doi.org/10.14456/apjcp.2016.148/APJCP.2016.17.7.3643 KSCI

Management of eyelid cancers is based on surgery and/or radiotherapy (RT). The treatment objective is to control tumors with acceptable functional and esthetic outcomes. The aim of this study was to evaluate the results of radiation therapy in management of epithelial eyelid cancers, reviewing retrospectively the clinical records of patients treated in our institution from January 1989 to December 2013. We focused on clinical and histological features, treatment characteristics, tolerance and disease control. One hundred and eight patients (62 men and 46 women) were enrolled, with a mean age of 61 years [ranges 15-87]. The most frequent tumor location was the inner canthus (42.6%). Median tumor size was 21 mm [ranges 4-70]. Histological type was basal cell carcinoma in 88 cases (81.5%), squamous cell carcinoma in 16 (14.8%) and sebaceous carcinoma in 4 (3.7%). Radiation therapy was exclusive in 67 cases (62%) and post-operative for positive or close margins in the remaining cases. Kilovoltage external beam radiotherapy (KVRT) was used in 63 patients (58.3%) and low-dose-rate interstitial brachytherapy in 37 (34.3%). Eight (7.4%) were treated with cobalt or with a combination of KVRT-cobalt, KVRT-electron beams, KVRT-brachytherapy or cobalt-electron beams. The total delivered radiation doses were 70 Gy (2 Gy/fraction) in 62 patients (57.4%), 66 Gy (2 Gy/fraction) in 37 (34.3%) and 61.2 Gy (3.4Gy/fraction) in 9 (8.3%). After a median follow-up of 64 months, we noted 10 cases of local recurrences(9.2%): 7 after exclusive and 3 after post-operative RT. No local recurrence occurred in patients treated with brachytherapy. Actuarial 5-year local recurrence-free rate, disease-free survival and overall survival were respectively 90%, 90% and 97%. T-stage was found to be a significant factor for recurrence (p=0.047). All acute radiation-related reactions were scored grade I or II. Delayed effects were eye watering in 24 cases (22.2%), eye dryness in 19 (17.6%), unilateral cataract in 7 (6.4%) and ectropion in 4 (3.7%). Radiation therapy and especially brachytherapy is an efficient treatment of eyelid cancers, allowing eye conservation and functional preservation with good local control rates and acceptable toxicity.

Phiphatpatthamaamphan, Kittichet;Vilaichone, Ratha-Korn 3647

https://doi.org/10.14456/apjcp.2016.149/APJCP.2016.17.7.3647 KSCI

Background: Colorectal cancer is one of the major health problems worldwide. However, limited studies have been reported from ASEAN countries. This study was conducted to evaluate clinical characteristics and survival of colorectal cancer cases aged <65 years and ${\geq}65$ years in the central region of Thailand. Materials and Methods: Clinical information, histological features, endoscopic findings and treatment outcome were collected and reviewed from Thammasat University Hospital, Pathumthani, Thailand between November 2011 and October 2015. Results: A total of 121 colorectal cancer patients, comprising 69 men and 52 women with a mean age of 65.8 years, were included. There were 57 aged <65 years and 64 aged ${\geq}65$ years. Common presenting symptoms were abdominal pain (37%), weight loss (34%) and anemia (32%). Mean duration of symptoms prior to diagnosis was 173 days. However, longer diagnosis time was demonstrated in patients aged <65 years than age more than ${\geq}65$ years (119.4 vs 58.4 days, P-value=0.30). Colonic fungating mass was the most common endoscopic finding (64.4%) and the location was significantly more commonly left than right side of the colon, both in younger and elderly groups (87.7% vs 12.3%, P=0.02 and 70.3% vs 29.7%, P=0.02, respectively). Adenocarcinoma with moderated differentiated was the most common histology (67.3%). More than half of the patients presented with advanced stage (28.9% with TNM stage 3 and 38.8% TNM stage 4, respectively). Overall 1-year and 5-year survival rates were 76.9% and 5%. Conclusions: Most colorectal cancer patients in Thailand have adenocarcinomas and present at advanced stage with poor prognosis. Screening of high risk patients and early detection might be essential factors to improve the treatment outcome and overall survival rate of colon cancer patients in Thailand and other ASEAN countries.

Alharbi, Abir;Tchier, F;Rashidi, MM 3651

https://doi.org/10.14456/apjcp.2016.150/APJCP.2016.17.7.3651 KSCI

Computer-aided diagnosis of breast cancer is an important medical approach. In this research paper, we focus on combining two major methodologies, namely fuzzy base systems and the evolutionary genetic algorithms and on applying them to the Saudi Arabian breast cancer diagnosis database, to aid physicians in obtaining an early-computerized diagnosis and hence prevent the development of cancer through identification and removal or treatment of premalignant abnormalities; early detection can also improve survival and decrease mortality by detecting cancer at an early stage when treatment is more effective. Our hybrid algorithm, the genetic-fuzzy algorithm, has produced optimized systems that attain high classification performance, with simple and readily interpreted rules and with a good degree of confidence.

Hariprasad, Roopa;Mehrotra, Ravi 3659

https://doi.org/10.14456/apjcp.2016.151/APJCP.2016.17.7.3659 KSCI

Hajihosseini, Morteza;Heidari, Samira;Alimohamadi, Samira 3661

https://doi.org/10.14456/apjcp.2016.152/APJCP.2016.17.7.3661 KSCI

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Volume 17 Issue 7

Asian Pacific Journal of Cancer Prevention

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Volume 17 Issue 7

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