Asian Pacific Journal of Cancer Prevention
아시아태평양암예방학회 (Asian Pacific Journal of Cancer Prevention)
- 월간
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- 1513-7368(pISSN)
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- 2476-762X(eISSN)
과학기술표준분류
- 보건의료 > 의약품/의약품개발
Aim & Scope
Cancer is a very complex disease. While many aspects of carcinoge-nesis and oncogenesis are known, cancer control and prevention at the community level is however still in its infancy. Much more work needs to be done and many more steps need to be taken before effective strategies are developed. The multidisciplinary approaches and efforts to understand and control cancer in an effective and efficient manner, require highly trained scientists in all branches of the cancer sciences, from cellular and molecular aspects to patient care and palliation. The Asia Pacific Organization for Cancer Prevention (APOCP) and its official publication, the Asia Pacific Journal of Cancer Prevention (APJCP), have served the community of cancer scientists very well and intends to continue to serve in this capacity to the best of its abilities. One of the objectives of the APOCP is to provide all relevant and current scientific information on the whole spectrum of cancer sciences. They aim to do this by providing a forum for communication and propagation of original and innovative research findings that have relevance to understanding the etiology, progression, treatment, and survival of patients, through their journal. The APJCP with its distinguished, diverse, and Asia-wide team of editors, reviewers, and readers, ensure the highest standards of research communication within the cancer sciences community across Asia as well as globally. The APJCP publishes original research results under the following categories: - Epidemiology, detection and screening. - Cellular research and bio-markers. - Identification of bio-targets and agents with novel mechanisms of action. - Optimal clinical use of existing anti-cancer agents, including combination therapies. - Radiation and surgery. - Palliative care. - Patient adherence, quality of life, satisfaction. - Health economic evaluations. All research and manuscript published by the Asia Pacific Journal of Cancer Prevention, are under the terms of the Creative Commons Attribution License. This permits anyone to copy, distribute, transmit and adapt the published work, provided the original work and source are appropriately cited. The APJCP strongly supports the Open Access initiative. Each published article is assigned a Crossref Digital Object Identifier (DOI), and full texts (HTML, PDF and XML format) of all articles published by the Asia Pacific Journal of Cancer Prevention, are freely accessible to everyone immediately after publication. Asia Pacific Journal of Cancer Prevention supports the Bethesda Statement on Open Access Publishing.
KSCI제16권3호
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Somi, Mohammad Hossein;Ghojazadeh, Morteza;Bagheri, Masood;Tahamtani, Taraneh 853
Background: Gastric cancer is the most common cancer in the Iranian population. The aim of this study was to determine the effect of clinicopathological factors on prognosis by meta-analysis. Materials and Methods: A literature search was conducted using MEDLINE, EMBASE and Cochrane library and extensive literature search using the Persian databases until February 2011. Prospective follow up studies with multivariate analysis of overall survival of the patients with gastric cancer were included in this review. The data were analyzed by CMA.2. Publication bias are checked by funnel plot and data are shown as Forest plots. Results: From a total of 63 articles, 14 retrospective studies which examined 5 prognostic factors and involving 10,500 patients were included. Tumor size (>35mm) was the main significant factor predicting an unfavorable prognosis for the patients with gastric cancer (RR=1.829, p<0.001) followed by presence of distant metastases (RR=1.607, p<0.001), poor differentiation (RR=1.408, p<0.001) and male sex (RR=1.194, p<0.001). Lymph node metastases (RR=1.058, p=0.698) and moderate differentiation (RR=0.836, p=0.043) were not statistically significant as prognostic factors. Conclusions: This meta-analysis suggests that tumor size>35mm, poor differentiation, presence of distant metastasis and male gender are strongly associated with a poor prognosis in Iranian patients with gastric cancer. -
Misra, Jata Shankar;Srivastava, Anand Narain;Das, Vinita 859
In view of funding crunches and inadequate manpower in cytology in developing countries like India, single lifetime screening for cervical cancer has been suggested. In this study, an attempt was made to cscreening to make it more effective for early detection. Cytological data were derived from the ongoing routine cervical cytology screening program for women attending Gynaecology Out Patient Department of Queen Mary's Hospital of K.G.Medical University, Lucknow, India during a span of 35 years (April 1971 - December 2005). Cervical smears in a total of 38,256 women were cytologically evaluated. The frequencies of squamous intraepithelial lesions of cervix (SIL) and carcinoma cervix were found to be 7.0% and 0.6%, respectively, in the series. Predisposing factors related to cervical carcinogenesis were analyzed in detail to establish the most vulnerable groups of women for single life time screening. The incidence of SIL and carcinoma cervix was found to be maximal in women above the age of 40 years irrespective of parity and in multiparous women (with three or more children) irrespective of age. The incidence of cervical cytopathologies was significantly higher in symptomatic women, the frequency of SIL being alarmingly higher in women complaining of contact bleeding and that of carcinoma cervix in older women with postmenopausal bleeding. It is consequently felt that single life time screening must include the three groups of women delineated above. Such selective screening appears to be the most economical, cost effective and feasible approach to affordably control the menace of cervical cancer in developing countries like India. -
Rabe, Shahrzad Taghizadeh;Emami, Seyed Ahmad;Iranshahi, Mehrdad;Rastin, Maryam;Tabasi, Nafise;Mahmoudi, Mahmoud 863
Background: Artemisia species are important medicinal plants throughout the world. The present in vitro study, using a sesquiterpene lactone-bearing fraction prepared from Artemisia khorassanica (SLAK), sought to investigate anti-cancer properties of this plant and elucidate potential underlying mechanisms for the effects. Materials and Methods: Anti-cancer potential was evaluated by toxicity against human melanoma and fibroblast cell lines. To explore the involved pathways, pattern of any cell death was determined using annexin-V/PI staining and also the expression of Bax and cytochrome c was investigated by Western blotting. Results: The results showed that SLAK selectively caused a concentration-related inhibition of proliferation of melanoma cells that was associated with remarkable increase in early events and over-expression of both Bax and cytochrome c. Conclusions: The current experiment indicates that Artemisia may have anti-cancer activity. We anticipate that the ingredients may be employed as therapeutic candidates for melanoma. -
Background: The prognostic value of microvessel density (MVD), reflecting angiogenesis, detected in ovarian cancer is currently controversial. Here we performed a meta-analysis of all relevant eligible studies. Materials and Methods: A comprehensive search of online PubMed, Medline, EMBASE and Sciencedirect was performed to identify all related articles. The search strategy was designed as 'microvessel density', 'ovarian cancer', 'ovarian neoplasm', 'CD34' and 'angiogenesis'. Results: The studies were categorized by author/year, number of patients, FIGO stage, histology, cutoff value for microvessel density, types of survival analysis, methods of hazard rations (HR) estimation, HR and its 95% confidence interval (CI). Combined hazard ratios suggested that high MVD was associated with poor overall survival (OS) and progression-free survival (PFS), with HR and 95% CIs of 1.84 (1.33-2.35) and 1.36 (1.06-1.66), respectively. Subgroup analysis showed that high MVD detected by CD34 was relevant for OS [HR=1.67 (1.36-2.35)], but not MVD detected with other antibodies [HR=2.11 (0.90-3.31)]. Another subgroup analysis indicated that high MVD in patients without pre-chemotherapy, but not with pre-chemotherapy, was associated with OS [HR=1.88(1.59-2.18 and HR=1.70 (-0.18-3.59)]. Conclusions: The OS and PFS with high MVD were significant poorer than with low MVD in ovarian cancer patients. However, high MVD detected by CD34 seems to be more associated with survival for patients without pre-chemotherapy.
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Wei, Ling;Wang, Xing-Wu;Sun, Ju-Jie;Lv, Li-Yan;Xie, Li;Song, Xian-Rang 875
Mediator 19 (Med19) is a component of the mediator complex which is a coactivator for DNA-binding factors that activate transcription via RNA polymerase II. Accumulating evidence has shown that Med19 plays important roles in cancer cell proliferation and tumorigenesis. The involvement of Med19 in sensitivity to the chemotherapeutic agent cisplatin was here investigated. We employed RNA interference to reduce Med19 expression in human non-small cell lung cancer (NSCLC) cell lines and analyzed their phenotypic changes. The results showed that after Med19 siRNA transfection, expression of Med19 mRNA and protein was dramatically reduced (p<0.05). Meanwhile, impaired growth potential, arrested cell cycle at G0/G1 phase and enhanced sensitivity to cisplatin were exhibited. Apoptosis and caspase-3 activity were increased when cells were exposed to Med19 siRNA and/or cisplatin. The present findings suggest that Med19 facilitates tumorigenic properties of NSCLC cells and knockdown of Med19 may be a rational therapeutic tool for lung cancer cisplatin sensitization. -
Donertas, Ayla;Nayki, Umit;Nayki, Cenk;Ulug, Pasa;Gultekin, Emre;Yildirim, Yusuf 881
Purpose: To analyze treatment modalities and prognostic factors in patients with Stage I-II endometrial stromal sarcoma (ESS). Materials and Methods: Twenty four patients (nineteen with low-grade ESS [LGESS] and five with high-grade ESS [HGESS]) were assessed retrospectively in terms of general characteristics, prognostic factors, treatment methods and survival. Results: Twenty patients were at Stage I and three were at Stage II. The stage of one patient could not be determined. With respect to age and comorbidity, no statistically significant difference was found among disease-free survival (DFS) (p=0.990; p=0.995). However, DFS was significantly shorter in Stage II than Stage I patients (p=0.002). It was also significantly shorter in HGESS patients than in LGESS patients (p=0.000). There was no statistically significant differences among the overall survival (OVS) times of patients with respect to age at diagnosis and comorbid disease (p=0.905; p=0.979) but OVS was significantly shorter in patients with HGESS (p=0.00) and Stage II disease (p=0.001). No statistically significant difference was found with respect to OVS between patients who received radiotherapy (RT) and those who did not receive RT (p=0.055). It was not statistically possible to include other treatment modalities in the analysis because of the small sample size. Conclusions: Grade and stage of a tumour were found to be the most important prognostic factors. It was not possible to determine the optimal surgical method and the effect of adjuvant treatment since the number of cases was insufficient. -
Haque, Shafiul;Akhter, Naseem;Lohani, Mohtashim;Ali, Arif;Mandal, Raju K. 889
Matrix metalloproteinase-2 (MMP2) is an endopeptidase, mainly responsible for degradation of extracellular matrix components, which plays an important role in cancer disease. A single nucleotide polymorphism (SNP) at -1306 disrupts a Sp1-type promoter site. The results from the published studies on the association between MMP2 -1306 C>T polymorphism and cancer risk are contradictory and inconclusive. In the present study, a meta-analysis was therefore performed to evaluate the strength of any association between the MMP2 -1306 C>T polymorphism and risk of cancer. We searched all eligible studies published on association between MMP2 -1306 C>T polymorphism and cancer risk in PubMed (Medline), EMBASE and Google Scholar online web databases until December 2013. Genotype distribution data were collected to calculate the pooled odds ratios (ORs) and 95% confidence intervals (95%CIs) to examine the strength of the association. A total of 8,590 cancer cases and 9,601 controls were included from twenty nine eligible case control studies. Overall pooled analysis suggested significantly reduced risk associated with heterozygous genotype (CT vs CC: OR=0.758, 95%CI=0.637 to 0.902, p=0.002) and dominant model (TT+CT vs CC: OR=0.816, 95%CI=0.678 to 0.982, p=0.032) genetic models. However, allelic (T vs C: OR=0.882, 95%CI=0.738 to 1.055, p=0.169), homozygous (TT vs CC: OR=1.185, 95%CI=0.825 to 1.700, p=0.358) and recessive (TT vs CC+CT: OR=1.268, 95%CI=0.897 to 1.793, p=0.179) models did not show any risk. No evidence of publication bias was detected during the analysis. The results of present meta-analysis suggest that the MMP2 -1306 C>T polymorphism is significantly associated with reduced risk of cancer. However, further studies with consideration of different populations will be required to evaluate this relationship in more detail. -
Mandal, Raju K.;Akhter, Naseem;Irshad, Mohammad;Panda, Aditya K.;Ali, Arif;Haque, Shafiul 897
PTEN (phosphatase and tensin homologue), as a tumor suppressor gene, plays a significant role in regulating cell growth, proliferation, and apoptosis. Results from published studies for association between the PTEN IVS4 I/D (rs3830675) polymorphism and cancer risk are inconsistent and inconclusive. We therefore conducted a meta-analysis to evaluate the potential association between PTEN IVS4 I/D polymorphism and risk of cancer in detail. We searched PubMed (Medline) and EMBASE web databases to cover all relevant studies published until December 2013. The meta-analysis was carried out and pooled odds ratios (ORs) and 95% confidence intervals (95%CIs) were used to appraise the strength of association. A total of 1,993 confirmed cancer cases and 3,200 controls were included from six eligible case-control studies. Results from overall pooled analysis suggested a significant effect of the PTEN IVS4 I/D polymorphism and cancer risk in all genetic models, i.e., allele (I vs D: OR=0.743, 95%CI=0.648 to 0.852, p=0.001), homozygous (II vs DD: OR=0.673, 95%CI=0.555 to 0.816, p=0.001), heterozygous (ID vs DD: OR=0.641, 95%CI=0.489 to 0.840, p=0.001), dominant (II+ID vs DD: OR=0.626, 95%CI=0.489 to 0.802, p=0.001) and recessive (II vs DD+ID: OR=0.749, 95%CI=0.631 to 0.889, p=0.001). Significant publication bias was detected during the analysis. The present meta-analysis suggests that the PTEN IVS4 I/D polymorphism is significantly associated with reduced risk of cancer. However, future larger studies with other groups of populations are warranted to clarify this association. -
Du, Feng;Yuan, Peng;Wang, Jia-Yu;Ma, Fei;Fan, Ying;Luo, Yang;Xu, Bing-He 903
Background: Among human epidermal growth factor receptor 2 (HER2)-positive breast cancer, more than half are also hormone receptor (HR)-positive. Although HR is a predictive factor for the efficacy of hormone therapy, there are still some uncertainties in regard to the effects on patients with HR-positive and HER2-positive metastatic breast cancers due to the potential resistance to hormone therapy caused by co-expression of HR and HER2. There are no clinical trials directly comparing the efficacy of hormonal therapy with chemotherapy. Materials and Methods: To examine the real-world effect of hormone therapy on patients with HR-positive and HER2-positive metastatic breast cancers, a cross-sectional study of a representative sample of the Chinese population was conducted. The study included 113 patients who received first-line and second-line palliative treatment between 2005 and 2010 in the Cancer Institute and Hospital, Chinese Academy of Medical Science. The effect of hormone therapy on overall survival (OS) was studied. Results: The patients who received hormone therapy (n=51) had better overall survival in contrast to those who received chemotherapy with anti-HER2 therapy (n=62) in first- or second-line treatment. The difference was of borderline statistical significance (51.8m vs 31.9m, p=0.065). In addition, the effect of hormone therapy did not differ significantly with other prognostic factors, including age (${\leq}50$ years or >50 years), disease free survival (${\geq}2$ years or < 2 years) and site of metastasis (visceral or bone/soft tissue). On multivariate analysis, administration of hormone therapy was associated with a trend toward a favorable prognosis (p=0.148, HR=0.693, 95%CI 0.422-1.139). Age more than 50 years was the sole independent harmful prognostic factor (p<0.001, HR=2.797, 95%CI 1.676-4.668). Conclusions: Our data suggest that hormonel therapy may improve outcomes of the patients with ER-positive and HER2-positive metastatic breast cancer. -
Liu, Yan;Yu, Qiu-Yan;Zhu, Zhen-Li;Tang, Ping-Yi;Li, Ke 909
Background: A systematic review and meta-analysis of observational studies evaluated the association of intake of vitamin B2 with the incidence of colorectal cancer. Materials and Methods: Relevant studies were identified in MEDLINE via PubMed (published up to April 2014). We extracted data from articles on vitamin B2 and used multivariable-adjusted odds ratio (OR) and a random-effects model for analysis. Results: We found 8 articles meeting the inclusion criteria (4 of cohort studies and 4 of case-control studies) and a total of 7,750 colorectal cancer cases were included in this meta-analysis. The multivariable-adjusted OR for pooled studies for the association of the highest versus lowest vitamin B2 intake and the risk of colorectal cancer was 0.83 (95% confidence interval [95%CI]:0.75,0.91). We performed a sensitivity analysis for vitamin B2. If we omitted the study by Vecchia et al., the pooled OR was 0.86 (95%CI, 0.77,0.96). Conclusions: This is the first meta-analysis to study links between vitamin B2 and colorectal cancer. We found vitamin B2 intake was inversely associated with risk of colorectal cancer. However, further research and large sample studies need to be conducted to better validate the result. -
Patra, Satyajit;Muthuraman, Meenakshi Sundaram;Prabhu, A.T.J. Ram;Priyadharshini, R. Ramya;Parthiban, Sujitha 915
Context: In the last half century, discovering, developing and introducing of clinical agents from marine sources have seen great successes, with examples including the anti-cancer compound trabectedin. However, with increasing need for new anticancer drugs, further exploration for novel compounds from marine organism sources is strongly justified. Objective: The major aim of this study was to evaluate the antitumor and antioxidant potential of Sargassum tenerrimum J.Agardh (Sargassaceae) on Ehrlich ascites carcinoma (EAC) in Swiss albino mice. Materials and Methods: An ethanol extract of S. tenerrimum (EEST) from whole algae was used to evaluate cytotoxicity followed by in vivo assessment of toxicity, using biochemical parameters including hepatic and non-hepatic enzymes. Antioxidant properties were examined in animals bearing EAC treated with daily oral administration of 100-300 mg/kg extract suspension. Results: Antitumor effects of EEST in EAC bearing mice was observed with LD50 1815 mg/kg. Parameters like body weight, tumor volume, packed cell volume, tumor cell count, mean survival time and increase in life span in animals in the EAC bearing animals treated with EEST 300 mg/kg was comparable with control group. Significant differences were also seen with changes in total protein content, hepatic enzymes contents, MDA level, and free radical scavenging enzymes in untreated vs. EEST treated group animals. Conclusions: Evaluation of antioxidant enzymes and hepatic enzymes in the EAC animal model treated with EEST exhibited similar effects as the positive control drug 5-flurouracil. S. tenerrimum extracts contain effective antioxidants with significant antitumor activity. -
Kose, Mesut;Celik, Fatih;Kose, Seda Kayman;Arioz, Dagistan Tolga;Yilmazer, Mehmet 923
Purpose: To determine whether the preoperative platelet to lymphocyte ratio (PLR) could predict invasiveness of cervical pathologies. Materials and Methods: Patients with preinvasive and invasive diseases were reviewed retrospectively, over a nine-year period, 2005-2014. The pathological records and completed blood counts of the patients were collected and recorded in the SPSS program. Patients were divided in two groups, preinvasive and invasive. Results: The median PLR was significantly higher in the invasive group than in the preinvasive group (p=0.03). There was a correlation between invasion of cervical cancer and white blood cell count, red cell distributing width (RDW), neutrophil-lymphocyte ratio (NLR), and PLR. Conclusions: This study showed that patients with uterine cervical cancer may present with leukocytosis, increased RDW, NLR and PLR. These cheap and easily available parameters, especially PLR, may provide useful information about the invasiveness of cervical lesions. -
Shankar, Abhishek;Rath, G.K.;Roy, Shubham;Malik, Abhidha;Bhandari, Ruchir;Kishor, Kunal;Barnwal, Keshav;Upadyaya, Sneha;Srivastava, Vivek;Singh, Rajan 927
Background: Breast and cervical cancers are the most common causes of cancer mortality among women in India, but actually they are largely preventable diseases. Although early detection is the only way to reduce morbidity and mortality, there are limited data on breast and cervical cancer knowledge, safe practices and attitudes of teachers in India. The purpose of this study is to assess the level of awareness and impact of awareness programs in adoption of safe practices in prevention and early detection. Materials and Methods: This assessment was part of a pink chain campaign on cancer awareness. During cancer awareness events in 2011 at various women colleges in different parts in India, a pre-test related to cervical cancer and breast cancer was followed by an awareness program. Post-tests using the same questionnaire were conducted at the end of the interactive session, at 6 months and 1 year. Results: A total of 156 out of 182 teachers participated in the study (overall response rate was 85.7 %). Mean age of the study population was 42.4 years (range- 28-59 yrs). There was a significant increase in level of knowledge regarding cervical and breast cancer at 6 months and this was sustained at 1 year. Adoption of breast self examination (BSE) was significantly more frequent in comparison to CBE, mammography and the Pap test. Magazines and newspapers were sources for knowledge regarding screening tests for breast cancer in more than 60% of teachers where as more than 75% were educated by doctors regarding the Pap test. Post awareness at 6 months and 1 year, there was a significant change in alcohol and smoking habits. Major reasons for not doing screening test were found to be ignorance (50%), lethargic attitude (44.8%) and lack of time (34.6%). Conclusions: Level of knowledge of breast cancer risk factors, symptoms and screening methods was high as compared to cervical cancer. There was a significant increase in level of knowledge regarding cervical and breast cancer at 6 months and this was sustained at 1 year. Adoption of BSE was significantly greater in comparison to CBE, mammography and the Pap test. To inculcate safe practices in lifestyle of people, awareness programmes such as pink chain campaign should be conducted more widely and frequently. -
Chen, Ying;Zhang, Lei;Liu, Wen-Xin;Liu, Xiang-Yu 933
Malignant tumors are often accompanied by increased risk of hematological abnormalities. However, few studies have reported any prognostic impact of preoperative thrombocytosis, leukocytosis and anemia in epithelia ovarian cancer (EOC). This study aimed to investigate preoperative hematological parameters for anemia, leukocytosis and thombocytosis in relation to established prognostic factors and survival in EOC cases. A total of 816 Chinese women treated for EOC were retrospectively included in the study focusing on the relationship between preoperative hemoglobin, leukocyte and platelet counts, and a panel of clinicopathologic characteristics and outcome. Preoperative anemia was present in 13.4%, leukocytosis in 16.7% and thrombocytosis in 22.8%. Additionally, EOC patients with low differentiation grade, advanced stage, lymph node (LN) metastasis, residual disease${\geq}1cm$ , ascites volume >1,000ml, serum cancer antigen 125 (CA125) >675U/ml, and disease recurrence had the higher prevalence of preoperative anemia, leukocytosis and thrombocytosis (all p<0.05). Moreover, EOC patients with older age or postmenopausal EOC patients had the higher prevalence of thrombocytosis (28.7% vs 17.3% or 26.0% vs 17.7%). Furthermore, in a Cox proportional hazard model, thrombocytosis was an independent factor for progression-free survival (PFS) and overall survival (OS) (p<0.001). Conclusively, preoperative anemia, leukocytosis or thrombocytosis in EOC patients is closely associated with more malignant disease phenotype and poorer prognosis. Significantly, thrombocytosis may independently predict the disease-specific survival for EOC patients. -
Liu, Yuan;Ma, Jing-Yue;Luo, Su-Ju;Sun, Chen-Wei;Shao, Li-Li;Liu, Quan-Zhong 941
Semaphoring is a transmembrane receptor which participates in many cytokine-mediated signal pathways that are closely related to the angiogenesis, occurrence and development of carcinoma. The present study was designed to access the effect of mono-antibody (mAb) guided radioimmunotherapy (RIT) on skin carcinoma and investigate the potential mechanisms. Semaphoring mAb was acquired from mice (Balb/c), purified with rProtein A column; purity, concentration and activity were tested with SDS-PAGE and indirect ELISA; specificity and expression on the cutanuem carcinoma line and tissue were tested by Western blotting; morphology change was assessed by microscopy. MTT assay and colony inhibition tests were carried out to test the influence on the proliferation of tumor cells; Western blotting was also carried out for expression of apoptosis-associated (caspase-3, Bax, Bcl-2) and proliferation-related (PI3K, p-Akt, Akt, p-ERK1/2, ERK1/2) proteins and analyse the change in signal pathways (PI3K/Akt and MEK/ERK). The purity of purified semaphorin mAb was 96.5% and the titer is about$1{\times}10^6$ . Western blotting showed semaphoring mAb to have specifically binding stripes with semaphoring b1b2 protein, B16F10, and A431 cells at 39KDa, 100KDa and 130KDa, respectively. Positive expression was detected both in cutanuem carcinoma line and tissue and it mostly located in cell membranes. MMT assay revealed dose-relate and time-relate inhibitory effect of semaphorin mAb on A431 and B16F10. Colony inhibition tests also showed dose-relate inhibitory effects. Western blotting demonstrated the expression of apoptosis and proliferation-related protein and changes in signal pathway. In conclusion, we demonstrated that semaphorin is highly expressed on the tumor cell-surfaces and RIT with semaphorin mAb has effect in i nhibiting proliferation and accelerating apoptosis of tumor cells. -
de Lima Pazine Campanholo, Vanessa Maria;Silva, Roseane Mendes;Silva, Tiago Donizetti;Neto, Ricardo Artigiani;Paiotti, Ana Paula Ribeiro;Ribeiro, Daniel Araki;Forones, Nora Manoukian 947
The aim of this study was to evaluate the effects of grape juice on colon carcinogenesis induced by azoxymethane (AOM) and expression of NF-kB, iNOS and TNF-${\alpha}$ . Methods: Forty male Wistar rats were divided into 7 groups: G1, control; G2, 15 mg/kg AOM; G3, 1% grape juice 2 weeks before AOM; G4, 2% grape juice 2 weeks before AOM; G5, 1% grape juice 4 weeks after AOM; G6, 2% grape juice 4 weeks after AOM; G7, 2% grape juice without AOM. Histological changes and aberrant crypt foci (ACF) were studied, while RNA expression of NF-kB, TNF- and iNOS was evaluated by qPCR. Results: The number of ACF was higher in G2, and G4 presented a smaller number of crypts per focus than G5 (p=0.009) and G6. Small ACF (1-3) were more frequent in G4 compared to G2, G5 and G6 (p=0.009, p=0.009 and p=0.041, respectively). RNA expression of NF-kB was lower in G3 and G4 compared to G2 (p=0.004 and p=0.002, respectively). A positive correlation was observed between TNF-${\alpha}$ and NF-kB gene expression (p=0.002). In conclusion, the administration of 2% grape juice before AOM reduced the crypt multiplicity, attenuating carcinogenesis. Lower expression of NF-kB was observed in animals exposed to grape juice for a longer period of time, regardless of concentration. -
Hartanto, Firstine Kelsi;Karen-Ng, Lee Peng;Vincent-Chong, Vui King;Ismail, Siti Mazlipah;Mustafa, Wan Mahadzir Wan;Abraham, Mannil Thomas;Tay, Keng Kiong;Zain, Rosnah Binti 953
Background: Expression of KRT13, FAIM2 and CYP2W1 appears to be influenced by risk habits, thus exploring the associations of these genes in oral squamous cell cancer (OSCC) with risk habits, clinico-pathological parameters and patient survival may be beneficial in identifying relevant biomarkers with different oncogenic pathways. Materials and Methods: cDNAs from 41 OSCC samples with and without risk habits were included in this study. Quantitative real-time PCR was used to analyze KRT13, FAIM2 and CYP2W1 in OSCC. The housekeeping gene (GAPDH) was used as an endogenous control. Results: Of the 41 OSCC samples, KRT13 was down-regulated in 40 samples (97.6%), while FAIM2 and CYP2W1 were down-regulated in 61.0% and 48.8%, respectively. Overall, there were no associations between KRT13, FAIM2 and CYP2W1 expression with risk habits, selected socio-demographic and clinico-pathological parameters and patient survival. Conclusions: Although this study was unable to show significance, there were some tendencies in the associations of KRT13, FAIM2 and CYP2W1 expression in OSCC with selected clinic-pathological parameters and survival. -
Abouzied, Mekky Mohammed;Eltahir, Heba M.;Fawzy, Michael Atef;Abdel-Hamid, Nabil Mohie;Gerges, Amany Saber;El-Ibiari, Hesham Mohmoud;Nazmy, Maiiada Hassan 959
Purpose: To find parameters that can increase alpha-fetoprotein (AFP) sensitivity and so help in accurate diagnosis and rapid management of hepatocullular carcinoma (HCC), as AFP has limited utility of distinguishing HCC from benign hepatic disorders for its high false-positive and false negative rates. Materials and Methods: Serum levels of AFP, 5'-nucleotidase enzyme activity (5-NU) and leucine aminopeptidase enzyme (LAP) activity were measured in 40 individuals. Results: LAP and 5'NU were elevated in HCC at p<0.001. Pearson correlation coefficients showed that changes in AFP exhibited positive correlation with both 5'-NU and LAP at (p<0.001). The complementary use of LAP only with AFP resulted in an increase in sensitivity of AFP from 75% to 90% in detecting HCC. The complementary use of both LAP and 5-NU with AFP resulted in an increased sensitivity of AFP in detecting HCC from 75% to 95%. Conclusions: LAP and 5-FU can be determined in HCC patients in combination with AFP to improve its sensitivity and decrease false negative results. -
Colorectal cancer is one of the most severe subtypes of cancer, and has the highest propensity to manifest as metastatic disease. Because of the lack of knowledge of events that correlate with tumor cell migration and invasion, few therapeutic options are available. The current study aimed to explore the mechanism of colorectal cancer in hope of identifying the ideal target for future treatment. We first discovered the pro-tumor effect of a controversial cell cycle regulator, cylin-dependent kinase inhibitor 3 (CDKN3), which is highly expressed in colorectal cancer, and the possible related signaling pathways, by bioinformatics tools. We found that CDKN3 had remarkable effects in suppressing colorectal cancer cell proliferation and migration, inducing cell cycle arrest and apoptosis in a colorectal cancer cell line, SW480 cells. Our study, for the first time, provided consistent evidence showing overexpression of cell cycle regulator CDKN3, in colorectal cancer. The in vitro studies in SW480 cells revealed a unique role of CDKN3 in regulating cellular behavior of colorectal cancer cells, and implied the possibility of targeting CDKN3 as a novel treatment for colorectal cancer.
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Qin, Jun-Jie;Liu, Zhao-Xia;Wang, Jun-Mei;Du, Jiang;Xu, Li;Zeng, Chun;Han, Wu;Li, Zhi-Dong;Xie, Jian;Li, Gui-Lin 971
Malignant glioblastoma multiforme (GBM) is the most malignant brain tumor and despite recent advances in diagnostics and treatment prognosis remains poor. In this retrospective study, we assessed the clinical and radiological parameters, as well as fluorescence in situ hybridization (FISH) of 1p19q deletion, in a series of cases. A total of 816 patients with GBM who received surgery and radiation between January 2010 and May 2014 were included in this study. Kaplan-Meier survival analysis and Cox regression analysis were used to find the factors independently influencing patient progression free survival (PFS) and overall survival (OS). Age at diagnosis, preoperative Karnofsky Performance Scale (KPS) score, KPS score change at 2 weeks after operation, neurological deficit symptoms, tumor resection extent, maximal tumor diameter, involvement of eloquent cortex or deep structure, involvement of brain lobe, Ki-67 and MMP9 expression level and adjuvant chemotherapy were statistically significant factors (p<0.05) for both PFS and OS in the univariate analysis. Cox proportional hazards modeling revealed that age${\leq}50$ years, preoperative KPS score${\geq}80$ , KPS score change after operation${\geq}0$ , involvement of single frontal lobe, deep structure involvement, low Ki-67 and MMP9 expression and adjuvant chemotherapy were independent favorable factors (p<0.05) for patient clinical outcomes. -
Noreen, Mamoona;Murad, Sheeba;Furqan, Muhammad;Sultan, Aneesa;Bloodsworth, Peter 979
Breast cancer is the leading cause of morbidity and mortality globally but has an even more significant impact in developing countries. Pakistan has the highest prevalence among Asian countries. A general lack of public awareness regarding the disease often results in late diagnosis and poor treatment outcomes. The literacy rate of the Southern Punjab (Pakistan) is low compared to its Northern part. It is therefore vital that university students and especially medical students develop a sound knowledge about the disease so that they can spread awareness to others who may be less educated. This study therefore considers current knowledge and understanding about the early signs of breast cancer amongst a study group of medical and non-medical university students of the Southern Punjab, Pakistan. A cross-sectional descriptive analysis of the university students was carried out using a self-administered questionnaire to assess their awareness of breast cancer from March to May 2014. A total of 566 students participated in this study, out of which 326 were non-medical and 240 were from a medical discipline. Statistical analysis was carried out using Graph Pad Prism Version 5 with a significance level set at p<0.05. The mean age of the non medical and medical participants was 23 (SD 2.1) and 22 (SD 1.3) years, respectively. Less than 35% students were aware of the early warning signs of the breast cancer development. Knowledge of medical students about risk factors was significantly better than the non medical ones, but on the whole was insufficient. Our study indicated that knowledge regarding breast cancer was generally insufficient amongst the majority of the university students (75% non-medical and 55% medical) of Southern Punjab, Pakistan. This study highlights the need to formulate an awareness campaign and to organize conferences to promote breast cancer awareness among students in this region. -
Turkeli, Mehmet;Aldemir, Mehmet Naci;Cayir, Kerim;Simsek, Melih;Bilici, Mehmet;Tekin, Salim Basol;Yildirim, Nilgun;Bilen, Nurhan;Makas, Ibrahim 985
Background: Docetaxel, cisplatin, 5-fluorouracil (DCF) given every three weeks is an effective, but palliative regimen and significantly toxic especially in patients who have a low performance score. Here, we aimed to evaluate the efficacy and tolerability of a weekly formulation of DCF in locally advanced and metastatic gastric cancer patients. Materials and Methods: 64 gastric cancer patients (13 locally advanced and 51 metastatic) whose ECOG (Eastern Cooperative Oncology Group) performance status (PS) was 1-2 and who were treated with at least two cycles of weekly DCF protocol as first-line treatment were included retrospectively. The weekly DCF protocol included$25mg/m^2$ docetaxel,$25mg/m^2$ cisplatin, and 24 hours infusion of$750mg/m^2$ 5-fluorouracil, repeated every week. Disease and patient characteristics, prognostic factors, treatment response, grade 3-4 toxicity related to treatment, progression free survival (PFS) and overall survival (OS) were evaluated. Results: Of the patients, 41 were male and 23 were female; the median age was 63 (29-82) years. Forty-one patients were ECOG-1 and 23 were ECOG-2. Of the total, 81.2% received at least three cycles of chemotherapy. Partial response was observed in 28.1% and stabilization in 29.7%. Overall, the disease was controlled in 57.8% whereas progression was noted in 42.2%. The median time to progression was 4 months (95%CI, 2.8-5.2 months) and median overall survival was 12 months (95%CI, 9.2-14.8 months). The evaluation of patients for grade 3-4 toxicity revealed that 10.9% had anemia, 7.8% had thrombocytopenia and 10.9% had neutropenia. Non-hematologic toxicity included renal toxicity (7.8%) and thrombosis (1.6%). Conclusions: In patients with locally advanced or metastatic gastric cancer who were not candidates for DCF administered every-3-weeks, a weekly formulation of DCF demonstrated modest activity with minimal hematologic toxicity, suggesting that weekly DCF is a reasonable treatment option for such patients. -
Jin, C.G.;Zou, T.N.;Li, J.;Chen, X.Q.;Liu, X.;Wang, Y.Y.;Wang, X.;Che, Y.H.;Wang, X.C.;Sriplung, Hutcha 991
Side population (SP) cells have stem cell-like properties with a capacity for self-renewal and are resistant to chemotherapy and radiotherapy. Therefore the presence of SP cells in human breast cancer probably has prognostic value. Objective: To investigate the characteristics of SP cells and identify the relationship between the SP cells levels and clinico-pathological parameters of the breast tumor and disease-free survival (DFS) in breast cancer patients. Materials and Methods: A total of 122 eligible breast cancer patients were consecutively recruited from January 1, 2006 to December 31, 2007 at Yunnan Tumor Hospital. All eligible subjects received conventional treatment and were followed up for seven years. Predictors of recurrence and/or metastasis and DFS were analyzed using Cox regression analysis. Human breast cancer cells were also obtained from fresh human breast cancer tissue and cultured by the nucleic acid dye Hoechst33342 with Verapami. Flow cytometry (FCM) was employed to isolate the cells of SP and non-SP types. Results: In this study, SP cells were identified using flow cytometric analysis with Hoechst 33342 dye efflux. Adjusted for age, tumor size, lymph nodal status, histological grade, the Cox model showed a higher risk of recurrence and/or metastasis positively associated with the SP cell level (1.75, 1.02-2.98), as well as with axillary lymph node metastasis (2.99, 1.76-5.09), pathology invasiveness type (1.7, 1.14-2.55), and tumor volume doubling time (TVDT) (1.54, 1.01-2.36). Conclusions: The SP cell level is independently associated with tumor progression and clinical outcome after controlling for other pathological factors. The axillary lymph node status, TVDT and the status of non-invasive or invasive tumor independently predict the prognosis of breast cancer. -
Yang, Guo-Tao;Wang, Juan;Xu, Tong-Zhen;Sun, Xue-Fei;Luan, Zi-Ying 997
Esophageal cancer represents the fourth most common gastrointestinal cancer and generally confers a poor prognosis. Prostaglandin-producing cyclo-oxygenase has been implicated in the pathogenesis of esophageal cancer growth. Here we report that prostaglandin dehydrogenase, the major enzyme responsible for prostaglandin degradation, is significantly reduced in expression in esophageal cancer in comparison to normal esophageal tissue. Reconstitution of PGDH expression in esophageal cancer cells suppresses cancer cell growth, at least in part through preventing cell proliferation and promoting cell apoptosis. The tumor suppressive role of PGDH applies equally to both squamous cell carcinoma and adenocarcinoma, which enriches our understanding of the pathogenesis of esophageal cancer and may provide an important therapeutic target. -
Liu, Li-Ya;Yu, Hao;Bai, Jian-Ling;Zeng, Ping;Miao, Dan-Dan;Chen, Feng 1001
Background: With development and application of new and effective anti-cancer drugs, the median survival post-progression (SPP) is often prolonged, and the role of the median SPP on surrogacy performance should be considered. To evaluate the impact of the median SPP on the correlation between progression-free survival (PFS) and overall survival (OS), we performed simulations for treatment of four types of cancer, advanced gastric cancer (AGC), metastatic colorectal cancer (MCC), glioblastoma (GBM), and advanced non-small-cell lung cancer (ANSCLC). Materials and Methods: The effects of the median SPP on the statistical properties of OS and the correlation between PFS and OS were assessed. Further, comparisons were made between the surrogacy performance based on real data from meta-analyses and simulation results with similar scenarios. Results: The probability of a significant gain in OS and HR for OS was decreased by an increase of the SPP/OS ratio or by a decrease of observed treatment benefit for PFS. Similarly, for each of the four types of cancer, the correlation between PFS and OS was reduced as the median SPP increased from 2 to 12 months. Except for ANSCLC, for which the median SPP was equal to the true value, the simulated correlation between PFS and OS was consistent with the values derived from meta-analyses for the other three kinds of cancer. Further, for these three types of cancer, when the median SPP was controlled at a designated level (i.e., < 4 months for AGC, < 12 months for MCC, and <6 months for GBM), the correlation between PFS and OS was strong; and the power of OS reached 34.9% at the minimum. Conclusions: PFS is an acceptable surrogate endpoint for OS under the condition of controlling SPPs for AGC, MCC, and GBM at their limit levels; a similar conclusion cannot be made for ANSCLC. -
Ibrahim, Noha Y.;Sroor, Mahmoud Y.;Darwish, Dalia O. 1007
Background: The clinical significance of bilateral breast cancer is unclear and its influence on prognosis is controversial. Materials and Methods: Between 2005 and 2009 we identified 110 cases of bilateral breast cancer (BBC) ; 49 patients had synchronous (duration between the occurrence of carcinoma in both breasts was less than 12 months) and 61 had metachronous (duration was more than one year with no ipsilateral local recurrence). We compared the patient characteristics including age, menopausal status, clinical stage, tumor size, histological classification, lymph node status, and hormone receptor and Her-2 status. We also compared the treatment given and overall and disease free survival (DFS) of both groups. Results: Synchronous cases tend to present more aggressively than metachronous cases and age at first presentation adversely affects survival. The 5 year overall survival was 78.7% for metachronous and 60% for synchronous. Patients with positive hormonal status had better five year disease free survival in metachronous compared to synchronous cases, at 76% and 63%, respectively. Age at first presentation >45years had better DFS (65%) compared to those with age${\leq}45$ years (52%) at 5 years follow up. Conclusions: Patients with synchronous breast cancer may have worse prognosis. Young age and hormone receptor negative were risk factors in our study. Close follow up and early detection of contralateral breast cancer is mandatory. -
Kotawong, Kanawut;Thitapakorn, Veerachai;Roytrakul, Sittiruk;Phaonakrop, Narumon;Viyanant, Vithoon;Na-Bangchang, Kesara 1011
This study was conducted to investigate the plasma phosphoproteome and differential plasma phosphoproteins in cases of of Opisthorchis viverrini (OV)-related cholangiocarcinoma (CCA). Plasma phosphoproteomes from CCA patients (10) and non-CCA subjects (5 each for healthy subjects and OV infection) were investigated using gel-based and solution-based LC-MS/MS. Phosphoproteins in plasma samples were enriched and analyzed by LC-MS/MS. STRAP, PANTHER, iPath, and MeV programs were applied for the identification of their functions, signaling and metabolic pathways; and for the discrimination of potential biomarkers in CCA patients and non-CCA subjects, respectively. A total of 90 and 60 plasma phosphoproteins were identified by gel-based and solution-based LC-MS/MS, respectively. Most of the phosphoproteins were cytosol proteins which play roles in several cellular processes, signaling pathways, and metabolic pathways (STRAP, PANTHER, and iPath analysis). The absence of serine/arginine repetitive matrix protein 3 (A6NNA2), tubulin tyrosine ligase-like family, member 6, and biorientation of chromosomes in cell division protein 1-like (Q8NFC6) in plasma phosphoprotein were identified as potential biomarkers for the differentiation of healthy subjects from patients with CCA and OV infection. To differentiate CCA from OV infection, the absence of both serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform and coiled-coil domain-containing protein 126 precursor (Q96EE4) were then applied. A combination of 5 phosphoproteins may new alternative choices for CCA diagnosis. -
Mahmood, Humera;Faheem, Mohammad;Mahmood, Sana;Sadiq, Maryam;Irfan, Javaid 1019
Background: Survival of breast cancer patients depends on a number of factors which are not only prognostic but are also predictive. A number of studies have been carried out worldwide to find out prognostic and predictive significance of different clinicopathological and molecular variables in breast cancer. This study was carried out at Nuclear Medicine, Oncology and Radiotherapy Institute (NORI), Islamabad, to find out the impact of different factors on overall survival of breast cancer patients coming from Northern Pakistan. Materials and Methods: This observational retrospective study was carried out in the Oncology Department of NORI Hospital. A total of 2,666 patients were included. Data were entered into SPSS 20. Multinomial logistic regression analysis was performed to determine associations of different variables with overall survival. P values <0.05 were considered significant. Results: The mean age of the patients was 47.6 years, 49.5% being postmenopausal. Some 1,708 were ER positive and 1,615 were PR positive, while Her 2 neu oncogene positivity was found in 683. A total of 1,237 presented with skin involvement and 426 had chest wall involvement. Some 1,663 had > 5cm tumors. Lymph node involvement was detected in 2,131. Overall survival was less than 5 years in 669 patients, only 324 surviving for more than 10 years, and in the remainder overall survival was in the range of 5-10 years. Conclusions: Tumor size, lymph node metastases, receptor status, her 2 neu positivity, skin involvement, and chest wall involvement have significant effects whereas age and menopausal status have no significant effect on overall survival of breast cancer patients in Pakistan. -
Liu, Yi-Qing;Zhang, Guo-An;Zhang, Bing-Chang;Wang, Yong;Liu, Zheng;Jiao, Yu-Lian;Liu, Ning;Zhao, Yue-Ran 1025
Background: Prostate cancer is one of the main causes of cancer death, and drug resistance is the leading reason for therapy failure. However, how this occurs is largely unknown. We therrfore aimed to study the response of DU145 cells to cisplatin. Materials and Methods: Du145 prostate cancer cells were treated with a low dose of cisplatin for 24 h and cell viability and number were determined by MTT assay and trypan blue exclusion assay, respectively. The real time polymerase chain reaction (PCR) was used to assess responses to cisplatin treatment. Results: After 24h$2{\mu}g/ml$ treatment did not result in significant reduction in cell viability or number. However, it led to enhanced cancer cell invasiveness. E-cadherin mRNA was reduced, and vimentin, Snail, Slug, metalloproteinase 9 (MMP9) mRNA expression increased significantly, a feature of epithelial-mesenchymal transition (EMT). Conclusions: Short time low concentration cisplatin treatment leads to elevated invasiveness of DU145 cancer cells and this is possibly due to EMT. -
Xiong, Xiao-Li;Qin, Huan;Yan, Su-Qi;Zhou, Li-Shan;Chen, Peng;Zhao, Dong-Chi 1029
Objective: Glypican-3 (GPC3) is reported to be an oncofetal protein that is a useful diagnostic immunomarker for hepatoblastoma. However, the results are not inclusive. This study systemically investigated the association between expression of GPC3 and pediatric hepatoblastoma. Methods: Clinical studies evaluating the association were identified using a predefined search strategy. GPC3 immunohistochemistry was applied in the pathological diagnosis of hepatoblastoma using the monoclonal antibodies with formalin-fixed and paraffin-embedded specimens. Positive predictive rates for the association between expression of GPC3 and pediatric hepatoblastoma were calculated. Results: Specimens from four clinical studies which including 134 patients with pediatric hepatoblastoma tested by GPC3 immunohistochemistry were considered eligible for inclusion. Systemic analysis showed that, in all patients, pooled positive predictive rate of the association between expression of GPC3 and pediatric hepatoblastoma was 95.5% (128/134). Conclusion: This systemic analysis suggests that the expression of glypican-3 is highly associated with the diagnosis of pediatric hepatoblastoma. -
Choubey, Vimal Kumar;Sankhwar, Satya Narayan;Carlus, S. Justin;Singh, Anand Narayan;Dalela, Divakar;Thangaraj, Kumarasamy;Rajender, Singh 1033
Background: Testosterone, a primary androgen in males, is converted into its most active form, dihydrotestosterone (DHT), by$5{\alpha}$ -reductase type 2 (encoded by the SRD5A2 gene) in the prostate. DHT is necessary for prostatic growth and has five times higher binding affinity than testosterone for androgen receptors. We hypothesized that polymorphic variations in the SRD5A2 gene may affect the risk of benign prostatic hyperplasia and prostate cancer. Materials and Methods: We analyzed SRD5A2 gene polymorphisms in 217 BPH patients, 192 PCa cases, and 171 controls. Genotyping was undertaken using direct DNA sequencing. Genotype data were compared between cases and controls using a Chi square statistical tool. Results: We found that the A49T locus was monomorphic with 'AA' genotype in all subjects. At V89L locus, the presence of 'VV' showed a marginally significant correlation with increased BPH risk (p=0.047). At the$(TA)_n$ locus, longer TA repeats were found to be protective against BPH (p=0.003). However, neither of these polymoprhisms correlated with the risk of PCa. Conclusions: We conclude that A49T is monomorphic in the study population, VV marginally correlates with BPH risk, and longer$(TA)_n$ repeats are protective against BPH. None of these polymorphisms affect the risk of PCa. -
Akhtar, Noreen;Bilal, Muhammad;Rizwan, Muhammad;Khan, Muhammad Asif;Khan, Aurangzeb 1037
Hepatitis C is a blood-borne infectious disease of liver, caused by a small enveloped, positive-single stranded RNA virus, called the hepatitis C virus (HCV). HCV belongs to the Flaviviridae family and has 6 genotypes and more than 100 subtypes. It is estimated that 185 million people are infected with HCV worldwide and 5% of these are in Pakistan. The study was designed to evaluate different genotypes of HCV circulating in District Mardan and to know about the behavior of these genotypes to different anti-viral regimes. In this study 3,800 patients were exposed to interferon alfa-2a plus Ribavirin treatment for 6-months and subjected to real-time PCR to check the viral response. Among these 3,677 (97%) patients showed no detectable HCV RNA while 123 (3%) patients (non-responders) remained positive for HCV RNA. Genotypes of their analyzed showed that most of them belonged to the 3a genotype. Non-responders (123) and relapsed (5) patients were subjected to PEG-interferon and Ribavirin therapy for next 6 months, which resulted into elimination of HCV RNA from 110 patients. The genotypes of the persisting resistant samples to anti-viral treatment were 3b, 2a, 1a and 1b. Furthermore, viral RNA from 6 patients remained un-typed while 4 patients showed mixed infections. HCV was found more resistant to antiviral therapy in females as compared to mals. The age group 36-45 in both females and males was found most affected by infection. In general 3a is the most prevalent genotype circulating in district Mardan and the best anti-viral therapy is PEG-interferon plus Ribavirin but it is common practice that due to the high cost patients receive interferon alfa-2a plus Ribavirin with consequent resistance in 3% patients given this treatment regime. -
Alikanoglu, Arsenal Sezgin;Yildirim, Mustafa;Suren, Dinc;Tutus, Birsel;Kaya, Vildan;Topal, Cumhur Selcuk;Keser, Sevinc;Karadayi, Ayse Nimet;Kapucuoglu, Fatma Nilgun;Ayva, Sebnem;Gunduz, Seyda 1041
Background: Paget's disease (PD) is a rare form of intraepithelial adenocarcinoma that involves breast and extramammarian tissues. It is often associated with ductal carcinoma in situ and/or invasive ductal cancer. Molecular pathways that play a role in development of Paget's disease are stil unclear. Expression patterns of Cox-2 and bcl-2 were therefore assessed. Materials and Methods: Patients with a histopathological diagnosis of Paget's disease were included in this study. Patient files were analysed retrospectively. Results: Invasive cancer was diagnosed in 35 (76.1%) of the patients, 7 (15.2%) had ductal carcinoma in situ and 4 (8.7%) patients had no associated neoplasm. Twenty four (52.2%) patients showed COX-2 expression in Paget cells whereas no expression was seen in 22 (47.8%) patients. No relation was found between COX-2 expression and the lesion underlying Paget's disease (p=0.518). Bcl-2 expression in Paget cells was found positive in 12 (26.1%) and negative in 27 (58,7%) cases. There was no relation between Bcl-2 expression and the lesion accompanying Paget's disease (p=0.412). No relation was observed between COX-2 expression and Bcl-2 expression (p=0.389). Conclusions: In breast cancer, COX-2 expression is associated with poor prognostic factors. As COX-2 expression increases the tendency to metastasize also increases. In our study we found a significantly high COX-2 expression in Paget's disease of the breast. We suggest that COX-2 expression and inflammatory processes may play a role in pathogenesis of the Paget's disease of the breast. -
Zhang, Yan;Cai, Feng;Liu, Liang;Liu, Xiao-Dong 1047
Background: This systematic analysis was conducted to investigate pathological diagnosis of vertebral tumor metastasis with unknown primaries. Methods: Clinical studies conducted to pathologically investigate vertebral tumor metastasis were identified using a predefined search strategy. Pooled diagnosis (PD) of each pathological confirmation was calculated. Results: For vertebral tumor metastasis, 5 clinical studies which included 762 patients were considered eligible for inclusion. Systematic analysis suggested that, for all patients with vertebral tumor metastasis, dominant PD was pathologically confirmed with lung cancer in 21.7% (165/762), with breast cancer in 26.6% (203/762) and with prostate cancer in 19.2% (146/762). Other diagnosis that could be confirmed included lymphoma, multiple myeloma, renal cancer, for example, in this cohort of patients. Conclusions: This systemic analysis suggested that breast, lung and prostate lesions could be the most common pathological types of cancer for vertebral tumor metastasis formunknown primaries, and other common diagnoses could include lymphoma, multiple myeloma, renal cancer. -
Wu, You-Sheng;Bao, Deng-Ke;Dai, Jing-Yao;Chen, Cheng;Zhang, Hong-Xin;Yang, YeFa;Xing, Jin-Liang;Huang, Xiao-Jun;Wan, Shao-Gui 1051
Aberrant expression of genes in de novo lipogenesis (DNL) pathway were associated with various cancers, including hepatocellular carcinoma (HCC). Single nucleotide polymorphisms (SNPs) of DNL genes have been reported to be associated with prognosis of some malignancies. However, the effects of SNPs in DNL genes on overall survival of HCC patients receiving transarterial chemoembolization (TACE) treatment are still unknown. In present study, nine SNPs in three genes (ACLY, ACACA and FASN) in DNL pathway were genotyped using the Sequenom iPLEX genotyping system in a hospital-based cohort with 419 HCC patients treated with TACE, and their associations with HCC overall survival were evaluated by Cox proportional hazard regression analysis under three genetic models (additive, dominant and recessive). Although we did not find any significant results in total analysis (all p>0.05), our stratified data showed that SNP rs9912300 in ACLY gene was significantly associated with overall survival of HCC patients with lower AFP level and SNP rs11871275 in ACACA gene was significantly associated with overall survival of HCC patients with higher AFP level. We further identified the significant interactions between AFP level and SNP rs9912300 or rs11871275 in the joint analysis. Conclusively, our data suggest that genetic variations in genes of DNL pathway may be a potential biomarker for predicting clinical outcome of HCC patients treated with TACE. -
Haddadi, Mahnaz;Muhammadnejad, Samad;Sadeghi-Fazel, Fariba;Zandieh, Zahra;Rahimi, Gohar;Sadighi, Sanambar;Akbari, Parya;Mohagheghi, Mohammad-Ali;Mosavi-Jarrahi, Alireza;Amanpour, Saeid 1057
Background: Since the survival rate of breast cancer patients has improved, harmful effects of new treatment modalities on fertility of the young breast cancer patients has become a focus of attention. This study aimed to systematically review and critically appraise all available guidelines for fertility preservation in young breast cancer patients. Materials and Methods: Major citation databases were searched for treatment guidelines. Experts from relevant disciplines appraised the available guidelines. The AGREE II Instrument that includes 23 criteria in seven domains (scope and purpose of the guidelines, stakeholder involvement, rigor of development, clarity, applicability, editorial independence, and overall quality) was used to apprise and score the guidelines. Results: The search strategy retrieved 2,606 citations; 72 were considered for full-text screening and seven guidelines were included in the study. There was variability in the scores assigned to different domains among the guidelines. ASCO (2013), with an overall score of 68.0%, had the highest score, and St Gallen, with an overall score of 24.7%, had the lowest scores among the guidelines. Conclusions: With the promising survival rate among breast cancer patients, more attention should be given to include specific fertility preservation recommendations for young breast cancer patients. -
Eichler, Christian;Pia, Multhaupt;Sibylle, Multhaupt;Sauerwald, Axel;Friedrich, Wolff;Warm, Mathias 1063
Background: Tumor associated fatigue (TAF) or cancer related fatigue (CRF) is not a new concept. Nonetheless, no real headway has been made in the quantitative analysis of its successful treatment via cognitive behavioral therapy. Since 20 to 30% of all breast cancer patients suffer from anxiety and/or depression within the first year of their diagnosis, this issue needs to be addressed and a standard treatment protocol has to be developed. This study focused on developing a simple, reproducible and short (8 weeks) protocol for the cognitive behavioral therapy support of tumor associated fatigue patients. Materials and Methods: Between the year 2011 and 2012, 23 breast cancer patients fulfilled the diagnosis TAF requirements and were introduced into this study. Our method focused on a psycho-oncological support group using a predetermined, highly structured and reproducible, cognitive behavioral therapy treatment manual. Eight weekly, 90 minute sessions were conducted and patients were evaluated before and after this eight session block. Tumor fatigue specific questionnaires such as the multidimensional fatigue inventory (MFI) as well as the hospital anxiety and depression scale (HADS) were used in order to quantitatively evaluate patient TAF. Results: Of the 23 patients enrolled in the study, only 7 patients fulfilled the TAF diagnostic criteria after the psycho-oncological group treatment. This represents a 70% reduction in diagnosable tumor associated fatigue. The HADS analysis showed a 33% reduction in patient anxiety as well as a 57% reduction in patient depression levels. The MFI scores showed a significant reduction in 4 of the 5 evaluate categories. With the exception of the "mental fatigue" MFI category all results were statistically significant. Conclusions: This study showed that a highly structured, cognitive behavioral therapy group intervention will produce significant improvements in breast cancer patient tumor associated fatigue levels after only 8 weeks. -
Ahmadi, Ali;Mosavi-Jarrahi, Alireza;Pourhoseingholi, Mohamad Amin 1069
Background: Colorectal cancer (CRC) is an important cause of mortality and morbidity in many communities worldwide. This population based study was conducted to assess determinants of colorectal mortality in Iranian patients. Materials and Methods: A cohort of 1,127 cases of confirmed colorectal cancer registered in a population based registry covering 10 referral hospital in Tehran, Iran, were followed for five years. Information about tumor characteristics, smoking status and family history were collected at base line and survival status were followed every six months by contacting patient or next of kin (if patients died during the follow-up). The cause of death for each case was validated by verbal autopsy and referring to patient medical records at the time of death. The data were analyzed by Stata software using univariate and multivariate analysis (Cox regression). In building the model a p value of less than 5% was considered as significant. Results: The age at diagnosis was$53.5{\pm}14$ years. Sixty one percent were male. Colorectal mortality among the patients was 96.9 person-years among men and 83 person-years among women. Seventy five percent of patients lived for 2.72 years, 50% for 5.83, and 25% for 13 years after the diagnosis of colorectal cancer. The age at diagnosis was significantly different between men and women (p<0.03). Higher tumor grade predicted higher death rate; the adjusted hazard ratios were 1.79 (95%CI, 0.88-3.61), 2.16 (95%CI, 1.07-4.37), and 3.1 (95%CI, 1.51-6.34) for grades II, III, and IV respectively when they were compared with grade I as reference. Ethnicity, marital status, family history of cancer, and smoking were related to survival with different degrees of magnitude. Conclusions: Among many factors related to survival among the colorectal patients, tumor grade and smoking showed the highest magnitudes of association. -
Li, Xiao-Feng;Guo, Xiao-Guang;Yang, Yong-Yan;Liu, Ai-Yong 1073
Background: To explore the relationship between CXCR4, CD133 co-expression and clinicopathological features as well as prognosis of patients with phase II~III colon cancer. Materials and Methods: Forty-nine paraffin-embedded samples of tumor tissue and epithelial tissue adjacent to cancer were collected from patients with colon cancer undergoing radical surgery in Baotou Cancer Hospital from January, 2010 to June, 2011. CXCR4 and CD133 expression was detected using immunohistochemistry and its relationship with clinicopathological features and the 3-year survival rate was analyzed. Results: In the tumor tissue and colonic epithelial tissue adjacent to cancer, the positive expression rates of CXCR4 were respectively 61.2% (30/49) and 8.16% (4/49), while those of CD133 being 36.7% (18/49) and 6.12% (3/49). CXCR4 and CD133 expression in tumor tissue was not related to patient age, gender, primary focal sites, tumor size, TNM staging, histological type, tumor infiltration depth and presence or absence of lymphatic metastasis, but CXCR4 and CD133 co-expression was associated with TNM staging and lymphatic metastasis. The 3-year survival rate of patients with CXCR4 and CD133 co-expression was 27.3% (3/11), and that of the remainderwas 76.3% (29/38), the difference being significant ($X^2=7.0206$ , p=0.0081). Conclusions: CXCR4 and CD133 co-expression may be a risk factor for poor prognosis of patients with stage II~III colon cancer. -
Chen, Hong;Zhao, Ji-Yi;Qian, Xu-Chen;Cheng, Zheng-Yuan;Liu, Yang;Wang, Zhi 1077
Recent studies have suggested that the RAS protein activator like-1 (RASAL1) functions as a tumor suppressor in vitro and may play an important role in the development of gastric cancer. However, whether or not RASAL1 suppresses tumor growth in vivo remains to be determined. In the present study, we investigated the role of RASAL1 in gastric carcinogenesis using an in vivo xenograft model. A lentiviral RASAL1 expression vector was constructed and utilized to transfect the human poorly differentiated gastric adenocarcinoma cell line, BGC-823. RASAL1 expression levels were verified by quantitative real-time RT-PCR and Western blotting analysis. Then, we established the nude mice xenograft model using BGC-823 cells either over-expressing RASAL1 or normal. After three weeks, the results showed that the over-expression of RASAL1 led to a significant reduction in both tumor volume and weight compared with the other two control groups. Furthermore, in xenograft tissues the increased expression of RASAL1 in BGC-823 cells caused decreased expression of p-ERK1/2, a downstream moleculein the RAS/RAF/MEK/ERK signal pathway. These findings demonstrated that the over-expression of RASAL1 could inhibit the growth of gastric cancer by inactivation of the RAS/RAF/MEK/ERK pathway in vivo. This study indicates that RASAL1 may attenuate gastric carcinogenesis. -
Irvin, Veronica L.;Hofstetter, C. Richard;Nichols, Jeanne F.;Chambers, Christina D.;Usita, Paula M.;Norman, Gregory J.;Kang, Sunny;Hovell, Melbourne F. 1083
Background: Compliance with California's smoke-free restaurant and bar policies may be more a function of social contingencies and less a function of legal contingencies. The aims of this study were: 1) to report indications of compliance with smoke-free legislation in Korean bars and restaurants in California; 2) to examine the demographic, smoking status, and acculturation factors of who smoked indoors; and 3) to report social cues in opposition to smoking among a sample of Koreans in California. Materials and Methods: Data were collected by telephone surveys administered by bilingual interviewers between 2007-2009, and included California adults of Korean descent who visited a Korean bar or restaurant in a typical month (N=2,173, 55% female). Results: 1% of restaurant-going participants smoked inside while 7% observed someone else smoke inside a Korean restaurant. Some 23% of bar-going participants smoked inside and 65% observed someone else smoke inside a Korean bar. Presence of ashtrays was related to indoor smoking in bars and restaurants. Among participants who observed smoking, a higher percentage observed someone ask a smoker to stop (17.6%) or gesture to a smoker (27.0%) inside Korean restaurants (N=169) than inside Korean bars (n=141, 17.0% observed verbal cue and 22.7% observed gesture). Participants who smoked inside were significantly younger and more acculturated than participants who did not. Less acculturated participants were significantly more to likely to be told to stop smoking. Conclusions: Ten years after implementation of ordinances, smoking appears to be common in Korean bars in California. -
Lotrean, Lucia Maria;Ailoaiei, Roxana;Popa, Monica;de Vries, Hein 1091
Cancers can be detected in early stages through awareness of suspicious symptoms or by specific actions undertaken by individuals or participation in medical checks or screening programmes. The present research had three objectives: to assess the knowledge of Romanian women who have relatives with cancer with regard to cancer symptoms and detection methods; to identify socio-demographics factors influencing their level of knowledge; provide information regarding the attitudes of women from the study regarding medical help-seeking in case of any symptom which might be associated with cancer. This cross-sectional study was performed in an oncological hospital from Cluj-Napoca, Romania. It involved 160 women aged 18-70 years, who had relatives with cancer. An anonymous questionnaire was filled in by the participants. The results showed that around 10% of the study sample recognized all the 8 listed symptoms associated with cancer and all the 7 listed methods for cancer detection. The results of the linear regression analyses show that the level of knowledge regarding both symptoms and methods for detection was higher among younger women (B=-0.390, p<0.01, respectively B=-0.260; p<0.01), among those living in urban areas (B=0.872, p<0.01, respectively B=0.676; p<0.01) and those having higher educational level (B=0.883, p<0.001, respectively B=0.536; p<0.001). The majority of the participants agreed with the importance of looking for medical help within weeks up to one month in case that a symptom which might be associated with cancer was observed. The study underlines the necessity that much more information should be given to women who have relatives with cancer about what they can do to detect cancer in an early stage. This is especially needed for older women, women living in rural areas and women having a lower educational level. -
Al-Naggar, Redhwan Ahmed;Jillson, Irene Anne;Abu-Hamad, Samir;Mumford, William;Bobryshev, Yuri V. 1097
Background: Few studies have explored the knowledge and attitudes of adolescents toward cancer prevention and treatment. This lack of research and its potential utility in the development of new educational initiatives and screening methods, or the reconstruction of existing ones, provided the impetus for this study. The primary research aim was to assess secondary school student knowledge of cancer and determine whether or not they possessed basic knowledge of cancer symptoms, risk factors, and treatments and to determine the relationship between cancer knowledge and key demographic factors. Materials and Methods: The Management and Science University conducted a cross-sectional study analyzing responses through cross-tabulation with the socio-demographic data collected. Results: The findings of our quantitative analysis suggest that Malaysian youth generally possess a moderate knowledge about cancer. Quantitative analyses found that socioeconomic inequalities and bias in education present as important factors contributing to cancer awareness, prevention, and treatment among Malaysian adolescents. Conclusions: The findings indicate that Malaysian youth generally possess a moderate knowledge about cancer but the current deficiencies in initiatives directed to cancer awareness continue to hinder the improvement in prevention of cancer among Malaysian adolescents. -
Wen, Xu;Zhang, He-Da;Zhao, Li;Yao, Yu-Feng;Zhao, Jian-Hua;Tang, Jin-Hai 1105
Chemoresistance is the most common cause of chemotherapy failure during breast cancer (BCA) treatment. It is generally known that the mechanisms of chemoresistance in tumors involve multiple genes and multiple signaling pathways,; if appropriate drugs are used to regulate the mechanisms at the gene level, it should be possible to effectively reverse chemoresistance in BCA cells. It has been confirmed that chemoresistance in BCA cells could be reversed by ginsenoside Rh2 (G-Rh2). Preliminary studies of our group identified some drugresistance specific miRNA. Accordingly, we proposed that G-Rh2 could mediate drug-resistance specific miRNA and corresponding target genes through the gene regulatory network; this could cut off the drug-resistance process in tumors and enhance treatment effects. G-Rh2 and breast cancer cells were used in our study. Through pharmaceutical interventions, we could explore how G-Rh2 could inhibit chemotherapy resistance in BCA, and analyze its impact on related miRNA and target genes. Finally, we will reveal the anti-resistance molecular mechanisms of G-Rh2 from a different angle in miRNA-mediated chemoresistance signals among cells. -
Yu, Jing-Ping;Lu, Wen-Bin;Wang, Jian-Lin;Ni, Xin-Chu;Wang, Jian;Sun, Zhi-Qiang;Sun, Su-Ping 1111
Background: To investigate the relationship between pathologic tumor response to concurrent chemoradiotherapy and variation of serum VEGF in patients with esophageal cancer. Materials and Methods: Forty six patients with esophageal cancer who were treated with concurrent chemo-radiotherapy were enrolled. Endoscopic and pathologic examination was conducted before and four weeks afterwards. Serum level of VEGF was documented before, four weeks later and after chemo-radiotherapy. The relationship between pathologic response and the variation of serum level of VEGF and its influence on the prognosis were investigated. Results: Serum level of VEGF decreased remarkably during and after chemo-radiotherapy in patients whose pathologic response was severe (F=5.393, 4.587, P(0.05). There were no statistical differences of serum VEGF level before, during and after chemo-radiotherapy for patients whose pathologic response was moderate or mild. There were 18 (85.7%), 7 (53.8%) and 6 patients (50.0%) whose serum VEGF level dropped in the severe, moderate and mild group, respectively, with significant differences among these groups (p=0.046). Two year survival rates of patients with severe, moderate and mild pathologic response were 61.9%, 53.8% and 33.3% respectively, and no statistically difference between severe and mild group regarding OS (p=0.245) was tested. Conclusions: Tumor pathologic response during chemo-radiotherapy and the changes of serum VEGF lever could predict curative effects of chemo-radiotherapy in patients with esophageal cancer. -
Prasaja, Yenny;Sutandyo, Noorwati;Andrajati, Retnosari 1117
Background: Cisplatin is still used as a first-line medication for solid tumors. Nephrotoxicity is a serious side effect that can decrease renal function and restrict applicable doses. This research aimed to obtain the profile of cisplatin-induced nephrotoxicity and its associated factors in adult cancer patients at Dharmais National Cancer Hospital (DNCH). Materials and Methods: The design was cross-sectional with data obtained from patient medical records. We retrospectively reviewed adult cancer patients treated with cisplatin${\geq}60mg/m^2$ for at least four consecutive chemotherapy cycles from August 2011 to November 2013. The nephrotoxicity criterion was renal function decline characterized by creatinine clearance <60 ml/min using the Cockroft-Gault (CG) equation. Results: Eighty-eight subjects received at least four chemotherapy cycles of cisplatin. The prevalence of cisplatin nephrotoxicity was 34.1%. Symptoms could be observed after the first cycle of chemotherapy, and the degree of renal impairment was higher with increased numbers of cycles (r=-0.946,$r^2=89.5%$ ). Factors that affected the decline of renal function were patient age (p=0.008, OR=3.433, 95%CI= 1.363-8.645) and hypertension (p=0.026, OR=2.931, 95%CI=1.120-7.670). Conclusions: Cisplatin nephrotoxicity occurred in more than one-third of patients after the fourth cycle of chemotherapy and worsened after each cycle despite preventive strategies such as hydration. The decline of renal function induced by cisplatin${\geq}60mg/m^2$ was affected by age and hypertension. -
Gultekin, Guldal Inal;Yilmaz, Seda Gulec;Kahraman, Ozlem Timirci;Atasoy, Hande;Dalan, A. Burak;Attar, Rukset;Buyukoren, Ahmet;Ucunoglu, Nazli;Isbir, Turgay 1123
Uterine leiomyomas (ULM), are benign tumors of the smooth muscle cells of the myometrium. They represent a common health problem and are estimated to be present in 30-70% of clinically reproductive women. Abnormal angiogenesis and vascular-related growth factors have been suggested to be associated with ULM growth. The angiotensin-I converting enzyme (ACE) is related with several tumors. The aim of this study was to identify possible correlation between ULM and the ACE I/D polymorphism, to evaluate whether the ACE I/D polymorphism could be a marker for early diagnosis and prognosis. ACE I/D was amplified with specific primer sets recognizing genomic DNA from ULM (n=72) and control (n=83) volunteers and amplicons were separated on agarose gels. The observed genotype frequencies were in agreement with Hardy-Weinberg equilibrium ($x^2=2.162$ , p=0.339). There was no association between allele frequencies and study groups ($x^2=0.623$ ; p=0.430 for ACE I allele,$x^2=0.995$ ; p=0.339 for ACE D allele). In addition, there were no significant differences between ACE I/D polymorphism genotype frequencies and ULM range in size and number ($X^2=1.760;$ p=0.415 for fibroid size,$X^2=0.342;$ p=0.843 for fibroid number). We conclude that the ACE gene I/D polymorphism is not related with the size or number of ULM fibroids in Turkish women. Thus it cannot be regarded as an early diagnostic parameter nor as a risk estimate for ULM predisposition. -
Elkablawy, Mohamed A.;Albasri, Abdulkader M. 1129
Background: The tissue microarray (TMA) is widely accepted as a fast and cost-effective research tool for in situ tissue analysis in modern pathology. However, the current automated and manual TMA techniques have some drawbacks restricting their productivity. Our study aimed to introduce an improved manual tissue miniarray (TmA) technique that is simple and readily applicable to a broad range of tissue samples. Materials and Methods: In this study, a conventional TV/radio telescopic antenna was used to punch tissue cores manually from donor paraffin embedded tissue blocks which were pre-incubated at$40^{\circ}C$ . The cores were manually transferred, organized and attached to a standard block mould, and filled with liquid paraffin to construct TmA blocks without any use of recipient paraffin blocks. Results: By using a conventional TV/radio antenna, it was possible to construct TmA paraffin blocks with variable formats of array size and number ($2-mm{\times}42$ ,$2.5-mm{\times}30$ ,$3-mm{\times}24$ ,$4-mm{\times}20$ and$5-mm{\times}12$ cores). Up to$2-mm{\times}84$ cores could be mounted and stained on a standard microscopic slide by cutting two sections from two different blocks and mounting them beside each other. The technique was simple and caused minimal damage to the donor blocks. H&E and immunostained slides showed well-defined tissue morphology and array configuration. Conclusions: This technique is easy to reproduce, quick, inexpensive and creates uniform blocks with abundant tissues without specialized equipment. It was found to improve the stability of the cores within the paraffin block and facilitated no losses during cutting and immunostaining. -
Background: The objective of this study was to investigate the MSCT characteristics of PTL in order to enhance the awareness of this uncommon entity among both clinicians and radiologists. Materials and Methods: The clinicopathological data and MSCT images of 27 patients with PTL were retrospectively reviewed. The MSCT appearances were classified into three types: type 1, solitary nodule surrounded by normal thyroid tissue; type 2, multiple nodules in the thyroid, and type 3, enlarged thyroid glands with a reduced attenuation with or without peripheral thin hyperattenuating thyroid tissue. Results: The patients were enrolled in the study with a mean age of 68 years (range, 51-86years) and compression symptoms or enlarged cervical lymph nodes at diagnosis. Hashimoto's thyroiditis was in 20 patients. All patients had non-Hodgkin lymphoma of B-cell in origin, including 22 cases of diffuse large B-cell lymphoma (DLBCL) and 5 of low-grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT). For MSCT appearance, type 1 pattern was observed in 2 patients, type 2 in 8, and seventeen type 3 in 17. The lesions occurred in more than one lobe with a mean maximal transverse diameter of 6.9 cm and an ill-defined margin. Most tumors showed a homogeneous attenuation equal to that of surrounding muscles before contrast and obvious enhancement after contrast. Cervical lymph node involvement and invasion of the trahea and (or) esophagus were mainly observed in patients with DLBCL. Conclusions: PTL should be clinically considered in elder patients presenting with a history of Hashimoto's thyroiditis and cervical lymphadenopathy. The MSCT characteristics of PTL includes a mass diffusely affecting more than one thyroid lobe, isointense to muscle and obvious enhancement before and after contrast. DLBCL, the most common histological subtype of PTL, is associated with a higher invasive tendency.
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Zhong, Yun-Hua;Peng, Hao;Cheng, Hong-Zhong;Wang, Ping 1139
In order to explore the association between cadherin 13 (CDH13) gene promoter methylation and lung carcinoma (LC) risk, we carried out a meta-analysis with searching of PubMed, Web of Science. Ultimately, 17 articles were identified and analysised by STATA 12.0 software. Overall, we found a significant relationship between CDH13 promoter methylation and LC risk (odds ratio=6.98, 95% confidence interval: 4.21-11.56, p<0.001). Subgroup analyses further revealed that LC risk was increased for individuals carrying the methylated CDH13 compared with those with unmethylated CDH13. Hence, our study identified a strong association between CDH13 gene promoter methylation and LC and highlighted a promising potential for CDH13 methylation in LC risk prediction. -
Zakiullah, Zakiullah;Ahmadullah, Ahmadullah;Khisroon, Muhammad;Saeed, Muhammad;Khan, Ajmal;Khuda, Fazli;Ali, Sajid;Javed, Nabila;Ovais, Muhammad;Masood, Nosheen;Khalil, Nasir Khan;Ismail, Mohammad 1145
Associations of GSTT1, GSTM1 and CYP1A1 gene variants with risk of developing oral cancer were evaluated in this study. A case-control study was conducted in Pashtun population of Khyber Pakhtunkhwa province of Pakistan in which 200 hospital based oral cancer cases and 151 population based healthy controls exposed to similar environmental conditions were included. Sociodemographic data were obtained and blood samples were collected with informed consent for analysis. GSTM1 and GSTT1 were analysed through conventional PCR method while specific RT-PCR method was used to detect CYP1A1 polymorphisms. Results were analyzed for conditional logistic regression model by SPSS version 20. The study shows that patients with either GSTM1 or GSTT1 null genotypes have significantly higher risk of oral cancer (adjusted odds (OR): (3.019 (1.861-4.898) and 3.011(1.865-4.862), respectively), which further increased when either one or both null genes were present in combination (adjusted odds (OR): (3.627 (1.981-6.642 and 9.261 (4.495-19.079), respectively). CYP1A1 rs4646903 gene variants individually showed weak association OR: 1.121 (0.717-1.752); however, in the presence of GSTM1 and/or GSTT1 null genotypes further increasing the association (adjusted odds (ORs): 4.576 (2.038-10.273), 5.593 (2.530-12.362) and 16.10 (3.854-67.260 for GSTM/GSTT null and CYP1A1 wild type, GSTM/GSTT either null and CYP1A1 variant alleles, and all 3 gene polymorphisms combinations, respectively). Our findings suggest that presence of GSTM1 and/or GSTT1 null genotypes along with variant alleles of CYP1A1 may be the risk alleles for oral cancer susceptibility in Pashtun population. -
Mosmann, Jessica P.;Monetti, Marina S.;Frutos, Maria C.;Kiguen, Ana X.;Venezuela, Raul F.;Cuffini, Cecilia G. 1151
Human papillomavirus (HPV) is responsible for one of the most frequent sexually transmitted infections. The first phylogenetic analysis was based on a LCR region fragment. Nowadays, 4 variants are known: African (Af-1, Af-2), Asian-American (AA) and European (E). However the existence of sub-lineages of the European variant havs been proposed, specific mutations in the E6 and LCR sequences being possibly related to persistent viral infections. The aim of this study was a phylogenetic study of HPV16 sequences of endocervical samples from C${\acute{o}}$ rdoba, in order to detect the circulating lineages and analyze the presence of mutations that could be correlated with malignant disease. The phylogenetic analysis determined that 86% of the samples belonged to the E variant, 7% to AF-1 and the remaining 7% to AF-2. The most frequent mutation in LCR sequences was G7521A, in 80% of the analyzed samples; it affects the binding site of a transcription factor that could contribute to carcinogenesis. In the E6 sequences, the most common mutation was T350G (L83V), detected in 67% of the samples, associated with increased risk of persistent infection. The high detection rate of the European lineage correlated with patterns of human migration. This study emphasizes the importance of recognizing circulating lineages, as well as the detection of mutations associated with high-grade neoplastic lesions that could be correlated to the development of carcinogenic lesions. -
Caszo, Brinnell;Khair, Muhammad;Mustafa, Mohd Habbib;Zafran, Siti Nor;Syazmin, Nur;Safinaz, Raja Nor Intan;Gnanou, Justin 1159
Background: The prevalence of smoking among secondary school children continues to remain unchanged over the last 3 decades even though awareness regarding the health effects of smoking is increasing. Common misconceptions about smoking and parental influence could be factors influencing future intentions to smoke among these students. Hence, we looked at the common misconceptions as well as student perceptions about their future intention to smoke among Form 4 students in Shah Alam, Malaysia. Materials and Methods: This study was conducted by distribution of a questionnaire developed as part of the Global Youth Tobacco Survey to Form 4 student in 3 schools at Shah Alam. Results: Prevalence of smoking (current smokers) was 7.5%. Almost half of the children came from families where one or both parents smoked and a third of the parents had no discussion regarding consequences of smoking with them. A large number of students were classified as "triers" as they had tried smoking and were unsure of whether they would not be smoking in the future. Contrary to our expectations, students generally felt smoking did make one feel more uncomfortable and helped one to reduce body weight. Most students seemed to be aware of the ill-effects of smoking on health. They felt they had received adequate information from school regarding the effects on smoking on health. Conclusions: Our study showed that even though Form 4 students in Shah Alam were knowledgeable about ill-effects of smoking and were taught so as part of their school curriculum, the prevalence of smoking was still high. Students in the "trier group" represent a potential group of future smokers and strategies targeting tobacco control may be aimed at tackling these vulnerable individuals. Efforts are also needed to help educate secondary school children about common misconceptions and dispel myths associated with cigarette smoking. -
Zhu, Hai-Li;Zou, Zhen-Ning;Lin, Pei-Xin;Li, Wen-Xia;Huang, Ye-En;Shi, Xiao-Xin;Shen, Hong 1165
Objective: To investigate the incidence of malignant transformation and P53 and P16 expression in teratomatous skin of ovarian mature cystic teratoma. Materials and Methods: Data on ovarian teratoma specimens in nearly 10 years were reviewed. P53 and P16 expression were detected by immunohistochemistry in 25 cases of teratomatous skin of ovarian mature cystic teratoma, 20 cases of squamous cell carcinoma and 2 cases of squamous cell carcinoma originated from teratomatous skin. Results: Of 1913 cases of ovarian mature cystic teratoma in nearly 10 years, only two cases of squamous cell carcinoma were found in teratomatous skin, with malignant transformation rate of 0.1045%. P53 expression was detected in 2 cases squamous cell carcinoma originated from teratomatous skin and P16 overexpression in one. There were no expressions of P53 and P16 in 25 cases of teratomatous skin of ovarian mature cystic teratoma. Of 20 cases of squamous cell carcinoma P53 overexpression (positive rate of 55%) was detected in 11 cases, P16 overexpression (positive rate of 35%) in 7 cases. The positive rates of P53 and P16 expression in squamous cell carcinomas were significantly higher than that in the teratomatous skins (p< 0.001, p= 0.002). Conclusions: There was low risk of malignant transformation in teratomatous skin of ovarian mature cystic teratoma which can be explained by lower P53 and P16 expressionin teratomas than that in squamous cell carcinoma. -
He, Hao;Sun, Yan-Ping;Zheng, Lei;Yue, Zheng-Gang 1169
Background: Paris polyphylla (Chinese name: Chonglou) had been traditionally used for a long time and shown anti-cancer action. Based on the previous study that paris polyphylla steroidal saponins (PPSS) induced cytotoxic effect in human lung cancer A549 cells, this study was designed to further illustrate the mechanisms underlying. Materials and Methods: The mechanisms involved in PPSS-induced A549 cell death were investigated by phase contrast microscopy and fluorescence microscopy, flow cytometry and western blot analysis, respectively. Results: PPSS decreased the proportion of viable A549 cells, and exposure of A549 cells to PPSS led to both apoptosis and autophagy. Apoptosis was due to activations of caspase-8, caspase-3, as well as cleavage of PARP, and autophagy was confirmed by up-regulation of Beclin 1 and the conversion from LC3 I to LC3 II. Conclusions: PPSS was able to induce lung cancer A549 cell apoptosis and autophagy in vitro, the results underlining the possibility that PPSS would be a potential candidate for intervention against lung cancer. -
Rahimi, Zohreh;Yari, Kheirolah;Rahimi, Ziba 1175
Background: Expression of matrix metalloproteinases (MMPs) is up-regulated in human cancers. The aim of present study was to investigate the role of MMP-9 C-1562T polymorphism and its interaction with MMP-2 C-735T polymorphism in susceptibility to breast cancer in a population from Western Iran with Kurdish ethnic background. Materials and Methods: The study sample of 205 individuals consisted of 101 breast cancer patients and 104 healthy subjects. MMP-9 C-1562T and MMP-2 C-735T variants were identified using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Results: Among 67.4% of studied patients the breast cancer developed in the third and forth decades of the life. The frequency of MMP-9 T allele was 17.3% in patients and 10.1% in controls. The presence of T allele significantly increased the risk of breast cancer by 1.87-fold [OR=1.87 (95% CI 1.05-3.33, p=0.035)]. The frequency of MMP-9 CT+TT genotype tended to be higher in those patients with a family history of cancer in first degree-relatives (36.8%) than those without a family history (28.3%, p=0.37). We observed an interaction between the MMP-9 -1562 T allele with MMP-2 -735 C allele that significantly increased the risk of breast cancer [OR=1.42 (95% CI 1.02-1.98, p=0.036)]. Conclusions: The present study demonstrated that MMP-9 C-1562T polymorphism alone and in combination with MMP-2 C-735T polymorphism increased the risk of breast cancer that might be a useful biomarker in identifying women at risk of developing breast cancer. Also, this study revealed that in most women from Western Iran breast cancer presents in third and fourth decades of life. -
Shiryazdi, Seyed Mostafa;Kargar, Saeed;Taheri-Nasaj, Hossein;Neamatzadeh, Hossein 1181
Background: Accurate measurement of breast mass size is fundamental for treatment planning. We evaluated performance of BreastLight apparatus in detection breast of masses with this in mind. Materials and Methods: From July 2011 to September 2013, a total of 500 women referred to mammography unit in Yazd, Iran for screening were recruited to this study. Performance of BreastLight in detection breast masses regard their sizeing, measured with clinical breast examination (CBE), mammography and sonography, was assessed. Sonographic and mammography examinations were performed according to breast density among women in two groups of women younger (n=105) and older (n=395) than 30 years. Size correlations were performed using Spearman rho analysis. Differences between mass size as assessed with the different methods (mammography, sonography, and clinical examination) and the BreastLight detection were analyzed using$X^2$ -trend test. Results: Performance of the BreastLight in detection of lesions smaller than or equal to 1 cm assessed by CBE, mammography and sonography was 4.4%,7.7% and 12.5% and for masses larger than 4 cm was 65%, 100% and 57.1%, respectively. The performance of BreastLight in detection was significantly increased with larger masses (p<0.001). Conclusions: We conclude that clinical measurement of breast cancer size is as accurate as that from mammography or ultrasound. Accuracy can be improved by the use of a simple formula of both clinical and mammographic measurements. -
Sonmez, Ozlem Uysal;Guclu, Ertugrul;Uyeturk, Ummugul;Esbah, Onur;Turker, Ibrahim;Bal, Oznur;Budakoglu, Burcin;Arslan, Ulku Yalcintas;Karabay, Oguz;Oksuzoglu, Berna 1185
Background: Chemotherapy-induced febrile neutropenia (FN) with solid tumors causes mortality and morbidity at a significant rate. The purpose of this study was to compare the effects of filgastrim and lenograstim started with the first dose of antibiotics in hospitalized patients diagnosed with FN. Materials and Methods: Between February 2009 and May 2012, 151 patients diagnosed with FN were evaluated, retrospectively. In those considered appropriate for hospitalization, convenient antibiotic therapy with granulocyte colony stimulating factors was started within first 30 minutes by completing necessary examinations in accordance with FEN guide recommendations. Results: In this study, 175 febrile neutropenia attacks in 151 patients were examined. Seventy three of the patients were male and 78 were female. The average age was 53.6 and 53.6, respectively. The most common solid tumor was breast carcinoma in 38 (25%). One hundred and five FN patients (58%) were those who received granulocyte colony stimulating factors as primary prophylaxis. Conclusions: While studies comparing both drugs generally involve treatments started for prophylaxis, this study compared the treatment given during the febrile neutropenia attack. Compared to lenograstim, filgastrim shortens the duration of hospitalization during febrile neutropenia attack by facilitating faster recovery with solid tumors. -
Li, Zhi;Ni, Cai-Fang;Zhou, Jin;Shen, Xiao-Chun;Yin, Yu;Du, Peng;Yang, Chao 1191
Background: Epidermal growth factor-like domain multiple 7 (EGFL7), recently identified as a secreted protein regulated by oxygen exposure, plays a critical role in promoting metastasis of hepatocellular carcinoma (HCC). Transcatheter arterial embolization (TAE) is widely used for treatment of HCC, resulting in hypoxia in tumors and surrounding liver tissues. Accordingly, we proposed the hypothesis that there could be a relationship between expression of EGFL7 and response to TAE. Materials and Methods: We established a rabbit VX2 liver tumor model using percutaneous puncture technique guided by computed tomography. TAE and sham embolization were performed and the results were confirmed by MRI 3 weeks after inoculation. We investigated the EGFL7 expression of the two groups at 6h and 3 days after intervention by means of immunohistochemistry and Western blotting. Results: Immunohistochemical staining demonstrated that the levels of EGFL7 protein significantly increased in the TAE-treated tumors compared with the control group at 6 hours (P=0.031) and 3 days (P=0.020) after intervention. Meanwhile, the relative EGFL7 protein detected in TAE group also up-regulated compared with the control group at 6 hours (P=0.020) and 3 days (P=0.024) after intervention. Conclusions: This study reveals an increase of EGFL7 expression in rabbit VX2 liver tumors after TAE. The role of EGFL7 in HCC, especially its biological behavior after TAE, needs further investigation. -
Sang, Yi;Cheng, Chun;Tang, Xiao-Feng;Zhang, Mei-Fang;Lv, Xiao-Bin 1197
Breast cancer metastasis is a major cause of cancer-related death in women. However, markers for diagnosis of breast cancer metastasis are rare. Here, we reported that TET1, a tumor suppressor gene, was downregulated and hypermethylated in highly metastatic breast cancer cell lines. Moreover, silencing of TET1 in breast cancer cells increased the migration and spreading of breast cancer cells. In breast cancer clinical samples, TET1 expression was reduced in LN metastases compared with primary tissues. Besides, the methylation level of the TET1 promoter was increased significantly in LN metastases. Taken together, these findings indicate that promoter hypermethylation may contribute to the downregulation of TET1 and could be used as a promising marker for diagnosis in patients with breast cancer metastasis. -
Background: Tobacco is consumed in both smoking and smokeless forms in India. About 35-40% of tobacco consumption in India is in the latter. The study objective was to describe the association between chewing tobacco and adult mortality. Materials and Methods: A case-control study was conducted in urban (Chennai city) and rural (Villupuram district) areas in Tamil Nadu state in South India. Interviewed in 1998-2000 about 80,000 families (48,000 urban and 32,000 rural) with members who had died during 1995-1998. These were the cases and their probable underlying cause of death was arrived at by verbal autopsy. Controls were 600,000 (500,000 urban, 100,000 rural) individuals from a survey conducted during 1998-2001 in the same two study areas from where cases were included. Results: Mortality analyses were restricted to non-smoking non-drinkers aged 35-69. The age, sex, education and study area adjusted mortality odds ratio was 30% higher (RR:1.3, 95%CI:1.2-1.4) in ever tobacco chewers compared to never chewers and was significant for deaths from respiratory diseases combined (RR:1.5, 95%CI:1.4-1.7), respiratory tuberculosis (RR:1.7, 95%CI:1.5-1.9), cancers all sites combined (RR:1.5, 95%CI:1.4-1.7) and stroke (RR:1.4, 95%CI:1.2-1.6). Of the cancers, the adjusted mortality odds ratio was significant for upper aero-digestive, stomach and cervical cancers. Chewing tobacco caused 7.1% of deaths from all medical causes. Conclusions: The present study is the first large study in India analysing non-smoking non-drinkers. Statistically significant excess risks were found among ever tobacco chewers for respiratory diseases combined, respiratory tuberculosis, stroke and cancer (all sites combined) compared to never tobacco chewers.
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Shankar, Abhishek;Roy, Shubham;Malik, Abhidha;Kamal, Vineet Kumar;Bhandari, Ruchir;Kishor, Kunal;Mahajan, M.K.;Sachdev, Jaineet;Jeyaraj, Pamela;Rath, G.K. 1207
Background: Breast cancer is by far the most frequent cancer of women (23 % of all cancers), ranking second overall when both sexes are considered together. Contralateral breast cancer (CBC) is becoming an important public health issue because of the increased incidence of primary breast cancer and improved survival. The present communication concerns a study to evaluate the role of various clinico-pathological factors on the occurrence of contralateral breast cancer. Materials and Methods: A detailed analysis was carried out with respect to age, menopausal status, family history, disease stage, surgery performed, histopathology, hormone receptor status, and use of chemotherapy or hormonal therapy. The diagnosis of CBC was confirmed on histopathology report. Relative risk with 95%CI was calculated for different risk factors of contralateral breast cancer development. Results: CBC was found in 24 (4.5%) out of 532 patients. Mean age of presentation was 43.2 years. Family history of breast cancer was found in 37.5% of the patients. There was statistically significant higher rate (83.3%) of CBC in patients in age group of 20-40 years with RR=11.3 (95% CI: 1.4, 89.4, p=0.006) seen in 20-30 years and RR=10.8 (95% CI:1.5-79.6, p=0.002) in 30-40 years as compared to older age of 60-70 years. Risk of development was higher in premenopausal women (RR=8.6, 95% CI: 3.5-21.3,$p{\leq}0.001$ ). Women with family history of breast cancer had highest rate (20.9%) of CBC (RR=5.4, 95% CI: 2.5-11.6,$p{\leq}0.001$ ). Use of hormonal therapy in hormone receptor positive patients was protective factor in occurrence of CBC but not significant (RR=0.7, 95% CI: 0.3-1.5, p=0.333). Conclusions: Younger age, premenopausal status, and presence of family history were found to be significant risk factors for the development of CBC. Use of hormonal therapy in hormone receptor positive patients might be protective against occurrence of CBC but did not reach significance. -
Namal, Esat;Ercetin, Candas;Tokocin, Merve;Akcali, Zafer;Yigitbas, Hakan;Yavuz, Erkan;Celebi, Fatih;Totoz, Tolga;Pamukcu, Ozgul;Saglam, Emel 1213
Background: Gastric cancer is the second most common cause of cancer- related deaths worldwide and ranks$11^{th}$ or$14^{th}$ among all deaths. Patients with advanced disease require supportive care along with the medical and/or surgical treatment. Aim: To assess the need for palliative care for patients with advanced tumours along with standard clinical therapy. Materials and Methods: Eighty-four patients with metastatic (stage 4) gastric cancer, including both patients who had received surgical treatment or not, were followed up in Bagcilar Training and Research Hospital, Division of Medical Oncology between 2011 and 2014. They were categorised as supportive care (-) (Group 1, n=37) and (+) groups (Group 2, n=47) and evaluated retrospectively. Results: Demographic characteristics of the patients were as follows: mean age, Group 1,$65.2{\pm}10.5$ years, Group$2,63.7{\pm}11.3$ years; male/female ratio, Group 1, 21/16, Group 2, 28/19; distribution of Eastern Cooperative Oncology Group (ECOG) performance scores of 0 and 1, Group 1, ECOG 0 (n=9) and 1 (n=14), Group 2, ECOG 0 (34) and 1 (n=13) (p<0.0001); patients receiving second-line, Group 1 (n=7) and Group 2 (n=22) (p<0.008) or third - line chemotherapy,Group 2 (n=6) (p<0.02); mortality rates, Group 1, (n=28; 75.6%) and Group 2 (n=30; 63.8%); progression-free survival (PFS) rates, Group 1,$17.4{\pm}6$ weeks, Group 2,$28.3{\pm}16.2$ weeks; statistically significant overall survival rates, Group 1,$20.8{\pm}8.2$ weeks and Group 2,$28.3{\pm}162$ weeks (p<0.01). Conclusions: The supportive care team (medical oncologist, general surgeon, internal medicine specialist, algologist, psychiatrist and radiologist) can play a role in the treatment of metastatic gastric tumours, with improvements shown in terms of the performance status of cases, eligibility of patients to be on chemotherapy programmes for longer duration and overall survival rates in Turkey. -
Forat-Yazdi, Mohammad;Neamatzadeh, Hossein;Sheikhha, Mohammad Hasan;Zare-Shehneh, Masoud;Fattahi, Mortaza 1219
Background: To date several common mutations in BRCA1 and BRCA2 associated with breast cancer have been reported in different populations. However, the common BRCA1 and BRCA2 mutations among breast cancer patients in Iran have not been described in detail. Materials and Methods: To comprehensively assess the frequency and distribution of the most common BRCA1 and BRCA2 mutations in Iranian breast cancer patients, we conducted this meta-analysis on 13 relevant published studies indentified in a literature search on PubMed and SID. Results: A total of 11 BRCA1 and BRCA2 distinct common mutations were identified, reported twice or more in the articles, of which 10 (c.2311T>C, c.3113A>G, c.4308T>C, c.4837A>G, c.2612C>T, c.3119G>A, c.3548A>G, c.5213G>A c.IVS16-92A/G, and c.IVS16-68A/G) mutations were in BRCA1, and 1 (c.4770A>G) was in BRCA2. The mutations were in exon 11, exon 13, intron 16, and exon 20 of BRCA1 and exon 11 of BRCA2. All have been previously reported in different populations. Conclusions: These meta analysis results should be helpful in understanding the possibility of any first true founder mutation of BRCA1/BRCA2 in the Iranian population. In addition, they will be of significance for diagnostic testing, genetic counseling and for epidemiological studies. -
Ishida, Kazuko;Ishida, Junko;Kiyoko, Kanda 1225
This study aims to clarify the psychosocial reactions of female patients with gynecological cancer undergoing chemotherapy and in the process of suffering from alopecia and to examine their nursing support. The target group comprised female patients who had received two or more cycles of chemotherapy, were suffering from alopecia, and were aged 30-65. Data were collected from semi-structured interviews, conducted from the time the patients were informed by their doctors that they might experience alopecia due to chemotherapy to the time they actually experienced alopecia and until they were able to accept the change. Inductive qualitative analysis was employed to close in on the subjective experiences of the cancer patients. The results showed the existence of six phases in the psychosocial reactions in the process of alopecia: phase one was the reaction after the doctor's explanation; phase two was the reaction when the hair starts to fall out; phase three was the reaction when the hair starts to intensely fall out; phase four was the reaction when the hair has completely fallen out; phase five was the reaction to behavior for coping with alopecia; and phase six was the reaction to change in interpersonal human relationships. The results also made it clear that there are five types of reaction patterns as follows: 1) treatment priority interpersonal relationship maintenance type; 2) alopecia agitated interpersonal relationship maintenance type; 3) alopecia agitated interpersonal relationship reduction type; 4) alopecia denial interpersonal relationship reduction type; and 5) alopecia denial treatment interruption type. It is important to find out which of the five types the patients belong to early during treatment and provide support so that nursing intervention that suits each individual can be practiced. The purpose of this study is to make clear the process in which patients receiving chemotherapy come to accept alopecia and to examine evidence-based nursing care on patients with strong mental distress from alopecia. -
Zaki, Seham Mahrous;Abdel-Azeez, Hala A.;El Nagar, Mona Roshdy;Metwally, Khaled Abdel-Aziz;Ahmed, Marwa M. Samir S. 1235
Background: Fragile histidine triad (FHIT) gene is a tumor suppressor gene which involved in breast cancer pathogenesis. Epigenetics alterations in FHIT contributes to tumorigenesis of breast cancer. Objective: Our objective was to study FHIT promoter region hypermethylation in Egyptian breast cancer patients and its association with clinicopathological features. Materials and Methods: Methylation-specific polymerase chain reaction was performed to study the hypermethylation of FHIT promoter region in 20 benign breast tissues and 30 breast cancer tissues. Results: The frequency of hypermethylation of FHIT promoter region was significantly increased in breast cancer patients compared to bengin breast disease patients. The Odd's ratio (95%CI) of development of breast cancer in individuals with FHIT promoter hypermethylation (MM) was 11.0 (1.22-250.8). There were also significant associations between FHIT promoter hypermethylation and estrogen, progesterone receptors negativity, tumor stage and nodal involvment in breast cancer pateints. Conclusions: Our results support an association between FHIT promotor hypermethylation and development of breast cancer in Egyptian breast cancer patients. FHIT promoter hypermethylation is associated with some poor prognostic features of breast cancer. -
Wang, Jia-Ni;Xu, Li-Hua;Zeng, Wei-Gen;Hu, Pan;Rabkin, Samuel D.;Liu, Ren-Rin 1241
Background: Thyroid carcinoma is the most common malignancy of the endocrine organs. Although the majority of thyroid cancer patients experience positive outcomes, anaplastic thyroid carcinoma is considered one of the most aggressive malignancies. Current therapeutic regimens do not confer a significant survival benefit, and new therapies are urgently needed. Oncolytic herpes simplex virus (oHSV) may represent a promising therapy for cancer. In the present study, we investigated the therapeutic effects of a third-generation HSV vector,$G47{\Delta}$ , on various human thyroid carcinoma cell lines in vitro. Two subcutaneous (s.c.) models of anaplastic thyroid carcinoma were also established to evaluate the in vivo anti-tumor efficacy of$G47{\Delta}$ . Materials and Methods: The human thyroid carcinoma cell line ARO, FRO, WRO, and KAT-5, were infected with$G47{\Delta}$ at different multiplicities of infection (MOIs) in vitro. The survival rates of infected cells were calculated each day. Two s.c. tumor models were established using ARO and FRO cells in Balb/c nude mice, which were intratumorally (i.t.) treated with either$G47{\Delta}$ or mock. Tumor volumes and mouse survival times were documented. Results:$G47{\Delta}$ was highly cytotoxic to different types of thyroid carcinomas. For ARO, FRO, and KAT-5, greater than 30% and 80% of cells were killed at MOI=0.01 and MOI=0.1, respectively on day 5. WRO cells displayed modest sensitivity to$G47{\Delta}$ , with only 21% and 38% of cells killed. In the s.c. tumor model, both of the anaplastic thyroid carcinoma cell lines (ARO and FRO) were highly sensitive to$G47{\Delta}$ ;$G47{\Delta}$ significantly inhibited tumor growth and prolonged the survival of mice bearing s.c. ARO and FRO tumors. Conclusions: The oHSV$G47{\Delta}$ can effectively kill different types of human thyroid carcinomas in vitro.$G47{\Delta}$ significantly inhibited growth of anaplastic thyroid carcinoma in vivo and prolonged animal survival. Therefore,$G47{\Delta}$ may hold great promise for thyroid cancer patients. -
Al-Balbeesi, Amal O.;Halwani, Mona;Alanazi, Mohammad;Elrobh, Mohammad;Shaik, Jilani P.;Khan, Akbar Ali;Parine, Narasimha Reddy 1247
Background: Psoriasis, a common cutaneous disorder characterized by inflammation and abnormal epidermal proliferation with a prevalence of 2-3% in the general population, may be linked to certain types of cancer. Several studies have reported an association between interleukin 10 (IL-10) variant polymorphisms and inflammatory diseases such as psoriasis vulgaris although the results vary according to the population studied. No studies have been performed in the Saudi population. The present study concerned novel variants and other genetic polymorphisms of the promoter and exonic regions of the IL10 gene in patients with moderate to severe psoriasis and potential differences in genotype compared to a group of healthy volunteers. Materials and Methods: Patients with moderate to severe psoriasis and healthy controls with no personal or family history of psoriasis were selected from the central region of Saudi Arabia. Polymorphisms of the IL 10 gene of both groups were genotyped. Results: We observed two novel variants in 5'UTR region of the promoter precursor with higher prevalence of the genotype with both wild-type alleles in patients compared to the healthy control group. The differences at positions -377 and -150 were significantly associated with disease, both the variants conferred strong protection against psoriasis in Saudi patients. Conclusions: This observation provides further support for the importance of the part that IL10 plays in the pathophysiology of this disease. Confirmation of our findings in larger populations of different ethnicities would provide evidence for the role of IL-10 in psoriasis. -
Chittrakul, Saranya;Charoenkwan, Kittipat;Wongpakaran, Nahathai 1251
Background: To compare prevalence of anxiety in ovarian cancer patients following primary treatment to that of normal women and to examine predicting factor. Materials and Methods: In this cross-sectional study, 56 ovarian cancer patients who had primary surgical treatment within the past five years (cancer group) and 56 age-matched women who attended an outpatient clinic for check-ups (non-cancer group) were recruited from June 2013 to January 2014. The hospital anxiety and depression scale (HADS), was used to determine anxiety level of the participants with the score of${\geq}11$ suggestive of anxiety. The prevalence of anxiety symptoms and mean HADS scores for anxiety were compared between the study groups. For those with ovarian cancer, associations of demographic and clinical factors with anxiety was examined. A p-value of <0.05 was considered significant. Results: Participants in the non-cancer group had higher rate of medical comorbidity, higher salary, and more frequent university education. The prevalence of anxiety was not different between the groups, at 7.1% each. The mean HADS scores for anxiety subscale were not significantly different between the groups, 5.0 in the cancer group vs 6.1 in the non-cancer group (p=0.09). On multivariable analysis, no demographic or clinical factors significantly associated with anxiety were identified. For the cancer group, no association between any particular factors and anxiety was demonstrated. Conclusions: The prevalence of anxiety in women with ovarian cancer following primary treatment was comparable to that of normal women seeking routine check-up. -
Shishodia, Nitin Pratap;Divakar, Darshan Devang;Al Kheraif, Abdulaziz Abdullah;Ramakrishnaiah, Ravikumar;Pathan, Akbar Ali Khan;Parine, Narasimha Reddy;Chandroth, Santhosh Vediyera;Purushothaman, Binu 1255
Background: Locally advanced head and neck cancer is generally incurable and has a short survival rate. This study aimed to evaluate symptom relief, disease response, and acute toxicity after palliative hypo-fractionated radiotherapy and long-term survival in affected patients. Materials and Methods: Between January 2011 to December 2011, 80 patients who were histopathologically diagnosed as having stage III or stage IV head and neck squamous cell carcinoma based on Eastern Cooperative Oncology Group (ECOG) performance status 1-3, were offered palliative radiotherapy (20 Gy/5Fr/5 Days). Later these patients were evaluated on 30th day after completion of treatment for disease response based on World Health Organisation (WHO) criteria and palliation of symptoms using symptomatic response grading and acute toxicities by the Radiation Therapy Oncology Group (RTOG). Many patients were given post radiation therapy (RT) palliative chemotherapy for appropriate palliative care and a few patients were selected for further curative RT. The overall survival was also evaluated among this group of patients with last follow up date of 1st May, 2014. Results: The most common presenting complaint was pain followed by dysphagia. Most patients (60-70%) had appreciable relief in their presenting symptoms. A good response was observed in the majority following palliative RT; a few patients had progressive disease and some had stable and regressed disease. None of the patients experienced radiation toxicity that required hospital admission. Almost all showed grade one and two acute skin and mucosal toxicity one month after completion of treatment. The mean survival days for patients given only hypofractionated palliative RT was 307 days, those with post palliative RT and palliative chemotherapy was 390 days and patients who went on to receive further palliative RT and curative RT dose had significantly overall survival of 582 days. Conclusions: Advanced head and neck cancer should be identified for suitable palliative hypofractionated radiotherapy to achieve acceptable symptom relief in a great proportion of patients and should be followed by palliative chemotherapy or curative RT in suitable cases for long-term symptom-free survival. -
Baade, Peter D.;Yu, Xue Qin;Smith, David P.;Dunn, Jeff;Chambers, Suzanne K. 1259
Background: This study reviewed the published evidence as to how prostate cancer outcomes vary across geographical remoteness and area level disadvantage. Materials and Methods: A review of the literature published from January 1998 to January 2014 was undertaken: Medline and CINAHL databases were searched in February to May 2014. The search terms included terms of 'Prostate cancer' and 'prostatic neoplasms' coupled with 'rural health', 'urban health', 'geographic inequalities', 'spatial', 'socioeconomic', 'disadvantage', 'health literacy' or 'health service accessibility'. Outcome specific terms were 'incidence', 'mortality', 'prevalence', 'survival', 'disease progression', 'PSA testing' or 'PSA screening', 'treatment', 'treatment complications' and 'recurrence'. A further search through internet search engines was conducted to identify any additional relevant published reports. Results: 91 papers were included in the review. While patterns were sometimes contrasting, the predominate patterns were for PSA testing to be more common in urban (5 studies out of 6) and affluent areas (2 of 2), higher prostate cancer incidence in urban (12 of 22) and affluent (18 of 20), greater risk of advanced stage prostate cancer in rural (7 of 11) and disadvantaged (8 of 9), higher survival in urban (8 of 13) and affluent (16 of 18), greater access or use of definitive treatment services in urban (6 of 9) and affluent (7 of 7), and higher prostate mortality in rural (10 of 20) and disadvantaged (8 of 16) areas. Conclusions: Future studies may need to utilise a mixed methods approach, in which the quantifiable attributes of the individuals living within areas are measured along with the characteristics of the areas themselves, but importantly include a qualitative examination of the lived experience of people within those areas. These studies should be conducted across a range of international countries using consistent measures and incorporate dialogue between clinicians, epidemiologists, policy advocates and disease control specialists. -
Mejri, N.;Boussen, H.;Labidi, S.;Bouzaiene, H.;Afrit, M.;Benna, F.;Rahal, K. 1277
Aim: To report epidemiologic and anatomoclinical transitions of inflammatory breast cancer (IBC) in Tunisia. Materials and Methods: Data including clinico-pathological data for 208 cases of T4d or PEV 3 non-metastatic breast cancer diagnosed between 2005 and 2010 were collected from patient records. Chi2 and Z tests were used to compare variables with two Tunisian historical series and a series about Arab-American patients. Results: Thirty three percent of our patients had their first child before 23 years of age and 56% had their menarche before 12 years, 75% never receiving oral contraception. Obesity was observed in 42% of women and IBC occurred during pregnancy in 13% of cases. Tumor grade was II-III in 90% of cases, HR was negative in 52%, HER2 was over expressed in 31% and invasion of more than 3 axillary nodes occurred in 18% of patients. We observed a pCR rate of 19% after neoadjuvant treatment (anthracyline-taxane used in 79%, trastuzumab in 27% ). Compared to historical Tunisian series (since 1996), IBC epidemiology remained stable in terms of median age, menopausal status and obesity. However we observed a significant decrease in median clinical tumor size and number of positive axillary lymph nodes. Comparison to IBC in Arab-Americans showed a significant difference in terms of median age, menopausal status, positivity of hormonal receptors and educational level. Conclusions: Our assessment of epidemiologic transition showed a reduction of clinco-pathological stage of IBC, keeping the same characteristics as compared to Tunisian historical series over a period of 14 years. Features seem to be different in Arab-American patients, probably related to migration, "occidentalization" of life style and improvement in socio-economic level. -
Zekri, Abdel-Rahman;Youssef, Amira Salah El-Din;Bakr, Yasser Mabrouk;Gabr, Reham Mohamed;El-Rouby, Mahmoud Nour El-Din;Hammad, Ibtisam;Ahmed, Entsar Abd El-Monaem;Marzouk, Hanan Abd El-Haleem;Nabil, Mohammed Mahmoud;Hamed, Hanan Abd El-Hafez;Aly, Yasser Hamada Ahmed;Zachariah, Khaled S.;Esmat, Gamal 1281
Background: Early detection of hepatocellular carcinoma using serological markers with better sensitivity and specificity than alpha fetoprotein (AFP) is needed. Aims: The aim of this study was to evaluate the diagnostic value of serum sICAM-1,${\beta}$ -catenin, IL-8, proteasome and sTNFR-II in early detection of HCC. Materials and Methods: Serum levels of IL-8, sICAM-1, sTNFR-II, proteasome and${\beta}$ -catenin were measured by ELISA assay in 479 serum samples from 192 patients with HCC, 96 patients with liver cirrhosis (LC), 96 patients with chronic hepatitis C (CHC) and 95 healthy controls. Results: Serum levels of proteasome, sICAM-1,${\beta}$ -catenin and${\alpha}FP$ were significantly elevated in HCC group compared to other groups (P-value<0.001), where serum level of IL-8 was significantly elevated in the LC and HCC groups compared to CHC and control groups (P-value <0.001), while no significant difference was noticed in patients with HCC and LC (P-value=0.09). Serum level of sTNFR-II was significantly elevated in patients with LC compared to HCC, CHC and control groups (P-value <0.001); also it was significantly higher in HCC compared to CHC and control groups (P-value <0.001). ROC curve analysis of the studied markers between HCC and other groups revealed that the serum level of proteasome had sensitivity of 75.9% and specificity of 73.4% at a cut-off value of$0.32{\mu}g/ml$ with AUC 0.803 sICAM-1 at cut off value of 778ng/ml, the sensitivity was 75.8% and the specificity was 71.8% with AUC 0.776.${\beta}$ -catenin had sensitivity and specificity of 70% and 68.6% respectively at a cut off value of 8.75ng/ml with an AUC of 0.729. sTNFR-II showed sensitivity of 86.3% and specificity of 51.8% at a cut off value of 6239.5pg/ml with an AUC of 0.722. IL-8 had sensitivity of 70.4% and specificity of 52.3% at a cut off value of 51.5pg/ml with AUC 0.631. Conclusions: Our data supported the role of proteasome, sICAM-1, sTNFR-II and${\beta}$ -catenin in early detection of HCC. Also, using this panel of serological markers in combination with${\alpha}FP$ may offer improved diagnostic performance over${\alpha}FP$ alone in the early detection of HCC. -
Sananpanichkul, Panya;Pittyanont, Sirida;Yuthavisuthi, Prapap;Thawonwong, Nutchanok;Techapornroong, Malee;Bhamarapravatana, Kornkarn;Suwannarurk, Komsun 1289
Background: Anal intraepithelial lesions (AIL) are likely to represent a precursor for anal cancer. Women infected with human immunodeficiency virus (HIV) may be at higher risk of anal cancer but a screening program for AIL still is not routinely recommended. We here studied the relationship of dysplastic cells from cervical and anal cytology in HIV-infected women. Materials and Methods: This prospective study was conducted in Prapokklao Hospital, Thailand during 2013-2014. Five hundred and ninety nine HIV-infected women were recruited. Participants who had cytological reports of equally or over "abnormal squamous/glandular cells of undetermined significance" (ASC-US) were classified as abnormal cervical or anal cytology. Descriptive statistics and logistic regression analysis were used to evaluate correlations between groups. Results: HIV-infected women with abnormal cervical cytology had 3.8 times more risk (adjusted odd ratio 3.846, 95% confidence interval 1.247-11.862, p-value. 019) for abnormal anal cytology. The major problem of the anal Pap test in this study was the inadequacy of the collected specimens for evaluation (34.4%, 206/599). Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of cervical and anal Pap tests were 93.9/12.0, 87.3/96.9, 39.7/21.4, 99.4/94.1 and 88.1/91.4 percent, respectively. Conclusions: Abnormal cervical cytology in HIV-infected women indicates elevated risk for abnormal anal cytology. The sensitivity of the anal Pap test for detection of AIL 2/3 in HIV-infected women was quite low while specificity was excellent. Inadequacy of specimen collection for evaluation was a major limitation. Improvement of sample collection is recommended for future investigations. -
Kim, So Young;Park, Jong-Hyock;Kang, Kyoung Hee;Hwang, Inuk;Yang, Hyung Kook;Won, Young-Joo;Seo, Hong-Gwan;Lee, Dukhyoung;Yoon, Seok-Jun 1295
Background: Cancer imposes a significant economic burden on individuals, families and society. The purpose of this study was to estimate the economic burden of cancer using the healthcare claims and cancer registry data in Korea in 2009. Materials and Methods: The economic burden of cancer was estimated using the prevalence data where patients were identified in the Korean Central Cancer Registry. We estimated the medical, non-medical, morbidity and mortality cost due to lost productivity. Medical costs were calculated using the healthcare claims data obtained from the Korean National Health Insurance (KNHI) Corporation. Non-medical costs included the cost of transportation to visit health providers, costs associated with caregiving for cancer patients, and costs for complementary and alternative medicine (CAM). Data acquired from the Korean National Statistics Office and Ministry of Labor were used to calculate the life expectancy at the time of death, age- and gender-specific wages on average, adjusted for unemployment and labor force participation rate. Sensitivity analysis was performed to derive the current value of foregone future earnings due to premature death, discounted at 3% and 5%. Results: In 2009, estimated total economic cost of cancer amounted to $17.3 billion at a 3% discount rate. Medical care accounted for 28.3% of total costs, followed by non-medical (17.2%), morbidity (24.2%) and mortality (30.3%) costs. Conclusions: Given that the direct medical cost sharply increased over the last decade, we must strive to construct a sustainable health care system that provides better care while lowering the cost. In addition, a comprehensive cancer survivorship policy aimed at lower caregiving cost and higher rate of return to work has become more important than previously considered. -
Studies of epidemiological and prognostic factors are very important for oncology practice. There is a rapidly increasing amount of research and resultant knowledge in the scientific literature. This means that health professionals have major challenges in accessing relevant information and they increasingly require best available evidence to make their clinical decisions. Meta-analyses of prognostic and other epidemiological factors are very practical statistical approaches to define clinically important parameters. However, they also feature many obstacles in terms of data collection, standardization of results from multiple centers, bias, and commentary for intepretation. In this paper, the obstacles of meta-analysis are briefly reviewed, and potential problems with this statistical method are discussed.