Asian Pacific Journal of Cancer Prevention
Asian Pacific Journal of Cancer Prevention (APOCP)
- Monthly
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- 1513-7368(pISSN)
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- 2476-762X(eISSN)
Domain
- Health Sciences > Development of Pharmaceutical
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.
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Daga, Aditi;Ansari, Afzal;Patel, Shanaya;Mirza, Sheefa;Rawal, Rakesh;Umrania, Valentina 4147
Lung cancer is a serious health problem and leading cause of death worldwide due to its high incidence and mortality. More than 80% of lung cancers feature a non-small cell histology. Over few decades, systemic chemotherapy and surgery are the only treatment options in this type of tumor but due to their limited efficacy and overall poor survival of patients, there is an urge to develop newer therapeutic strategies which circumvent the problems. Enhanced knowledge of translational science and molecular biology have revealed that lung tumors carry diverse driver gene mutations and adopt different intracellular pathways leading to carcinogenesis. Hence, the development of targeted agents against molecular subgroups harboring critical mutations is an attractive approach for therapeutic treatment. Targeted therapies are clearly more preferred nowadays over systemic therapies because they target tumor specific molecules resulting with enhanced activity and reduced toxicity to normal tissues. Thus, this review encompasses comprehensive updates on targeted therapies for the driver mutations in non-small cell lung cancer (NSCLC) and the potential challenges of acquired drug resistance faced i n the field of targeted therapy along with the imminent newer treatment modalities against lung cancer. -
Sakarya, Derya Kilic;Yetimalar, M Hakan;Ozbasar, Demir 4157
Treatment of early stage ovarian cancer remains controversial despite advances in chemotherapeutic options. Over the past 30 years, molecular and clinicopathologic studies accelerated and treatment of ovarian cancer has undoubtedly improved although there is a debate as to whether this impacts outcome or not. More recently, the introduction of targeted therapy started a new era. Probably it is because early stage disease comprises a small portion of the epithelial ovarian cancer, studies have mostly ignored this group and still there is no clear consensus regarding systemic treatment of early-stage lesions. However this group of patients has the best chance of cure. In this review, we focus on current developments in the treatment of early stage ovarian cancer and query the options. -
Pietrzyk, Lukasz;Torres, Anna;Maciejewski, Ryszard;Torres, Kamil 4161
Colorectal cancer (CRC) is a worldwide health problem, being the third most commonly detected cancer in males and the second in females. Rising CRC incidence trends are mainly regarded as a part of the rapid 'Westernization' of life-style and are associated with calorically excessive high-fat/low-fibre diet, consumption of refined products, lack of physical activity, and obesity. Most recent epidemiological and clinical investigations have consistently evidenced a significant relationship between obesity-driven inflammation in particular steps of colorectal cancer development, including initiation, promotion, progression, and metastasis. Inflammation in obesity occurs by several mechanisms. Roles of imbalanced metabolism (MetS), distinct immune cells, cytokines, and other immune mediators have been suggested in the inflammatory processes. Critical mechanisms are accounted to proinflammatory cytokines (e.g. IL-1, IL-6, IL-8) and tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$ ). These molecules are secreted by macrophages and are considered as major agents in the transition between acute and chronic inflammation and inflammation-related CRC. The second factor promoting the CRC development in obese individuals is altered adipokine concentrations (leptin and adiponectin). The role of leptin and adiponectin in cancer cell proliferation, invasion, and metastasis is attributable to the activation of several signal transduction pathways (JAK/STAT, mitogen-activated protein kinase (MAPK), phosphatidylinositol 3 kinase (PI3K), mTOR, and 5'AMPK signaling pathways) and multiple dysregulation (COX-2 downregulation, mRNA expression). -
Abbasi, Mehran Mesgari;Helli, Sanaz;Monfaredan, Amir;Jahanban-Esfahlan, Rana 4169
Background: Oral carcinoma (OC) remains as one of the most difficult malignancies to cure. Hesa-A is an Iranian herbal-marine compound that has shown promising anti-tumor properties on various human cancer cells, although the mechanisms of action remain to be addressed. This study was conducted to evaluate the effect of two doses of Hesa-A on mRNA expression of p53 as a main prognosticator of OC. Materials and Methods: 60 rats were randomly divided into 5 groups of 12 animals each. Rats in carcinoma groups received 0, 250 and 500 mg/kg body weight of Hesa-A three times a day. The two other groups considered as treated and untreated healthy groups. At the end of experiment, animals were sacrificed and tongue tissues subjected to H and E staining and real time PCR. Results: Our results indicated that compared to healthy group, p53 over expressed ~ 40% in untreated carcinoma group. After treatment with 250mg/kg and 500mg/kg body weights of Hesa-A, p53 level dropped by 53.4% and 13.6 %, respectively, compared to untreated carcinoma group (p<0.05, p<0.0001). Moreover, there was a significant relation between p53 mRNA content and observed pathological changes in studied groups (p<0.05). Conclusions: These data provide insights into the mechanism(s) by which Hesa-A improves clinical outcome of oral carcinoma by modulation of p53 expression. -
Chaiputcha, Kusumaporn;Promthet, Supannee;Bradshaw, Peter 4173
The aim of this cross-sectional analytic study was to investigate the prevalence and risk factors for Opisthorchis viverrini (OV) infection in an urban area of Northeastern Thailand. The participants were 254 household representatives aged 15 years or older living in the most urbanised part of Chiang Yuen municipality in Mahasarakham Province. All participants provided stool samples which were examined using the modified Kato-Katz procedure, and a structured interview questionnaire was used to collection demographic information, knowledge about OV infection, and the consumption of unsafely prepared freshwater fish. The data were analyzed using descriptive statistics and logistic regression. The overall prevalence of OV infection was 15.0%, and in the multivariate analysis male gender was found to be significantly and positively associated with OV infection ($OR_{adj}=9.75$ , 95%CI: 34.03-23.58) while education to secondary school level or above was a significant protective factor ($OR_{adj}=0.30$ , 95%CI: 0.12-0.74). The eating of unsafely prepared fish and knowledge about OV were not significantly related to infection status. The findings were discussed in terms of issues for future research, especially the need to consider the possibility of higher rates of OV infection in urban areas than might be expected and to investigate the sources of infected fish products which may well be different from those in rural villages. -
Zhou, Lei;Yu, Lan;Feng, Zhen-Zhong;Gong, Xiao-Meng;Cheng, Ze-Nong;Yao, Nan;Wang, Dan-Na;Wu, Shi-Wu 4177
Background: Gastric cancer is the second leading cause of cancer-related death in Asia, and the majority type is gastric adenocarcinoma (GAC). Most GAC patients die of recurrence and metastasis. Cancer stem cells (CSCs) have been thought to be responsible for the initiation, development, metastasis, and ultimately recurrence of cancer. In this study, we aimed to investigate expression and clinical significance of CSCs markers, CD133 and Lgr5, and vasculogenic mimicry (VM) in primary GAC. Materials and Methods: Specimens from 261 Chinese patients with follow-up were analyzed for CD133, Lgr5 protein expression and VM by immunohistochemical and histochemical staining. The Pearson Chi's square test was used to assess the associations among the positive staining of these markers and clinicopathological characteristics. Postoperative overall survival time was were studied by univariate and multivariate analyses. Results: In GAC tissues, positive rates of 49.0%, 38.7%, and 26.8% were obtained for CD133, Lgr5, and VM, respectively. The mean score of microvessel density (MVD) was$21.7{\pm}11.1$ in GAC tissues. There was a significantly difference between the positive and negative groups. There was a positive relationship between the VM, the expression of CD133 and Lgr5, and the score of MVD and the grades of tumor, lymph node metastasis, TNM stages (all p<0.05). The overall mean survival time of the patients with CD133, Lgr5, VM, and MVD (${\geq}22$ ) positive expression was lower than that of patients with negative expression. The score of MVD, positive expression of CD133 and VM were independent prognostic factors of GAC (p<0.05). Conclusions: VM, and expression of CD133, Lgr5, and the score of MVD are related to grades of tumor, lymph node metastasis, TNM stages, and overall mean survival time. It is suggested that CSCs and VM could play an important role in the evolution of GAC. -
Tajaddini, Aynaz;Pourzand, Ali;Sanaat, Zohreh;Pirouzpanah, Saeed 4185
Background: A protective effect of resistant starch (RS) containing foods on carcinogenesis has been shown from several lines of experimental evidence for gastrointestinal cancers. Therefore, we aimed to investigate the association between RS contained foods and breast cancer (BC) risk in a hospital-based, age- and origin-matched, case-control study. Materials and Methods: A validated, semi-quantitative, food frequency questionnaire (FFQ) was completed by 306 women newly diagnosed with BC aged 25 to 65 years, and 309 healthy women as matched controls. Odds ratios (ORs) and 95% confidence intervals (95%CI) were estimated using conditional logistic regression models. Results: Reduced BC risk was associated with the highest tertile of whole-wheat bread and boiled potato consumption with adjusted ORs at 0.34 (95%CI: 0.19-0.59) and 0.61 (95%CI: 0.37-0.99), respectively. Among consumers of whole-wheat bread, the protective role of cereals remained relatively apparent at higher intakes level of fiber rich breads at adjusted models (OR=0.53, 95%CI: 0.28-1.01). Moreover, high intake of legumes was found out to be a significant protective dietary factor against risk of BC development with an OR of 0.01 (95%CI: 0.03-0.13). However, consumption of white bread and biscuits was positively related to BC risk. Conclusions: Our results show that certain RS containing foods, in particular whole wheat bread, legumes and boiled potato may reduce BC risk, whereas higher intake of white bread and biscuits may be related to increased BC risk. -
Rangamani, Sukanya;SathishKumar, Krishnan;Manoharan, N;Julka, Pramod Kumar;Rath, Goura Kishor;Shanta, Viswanathan;Swaminathan, Rajaraman;Rama, Ranganathan;Datta, Karabi;Mandal, Syamsundar;Koyande, Shravani;Deshmane, Vinay;Ganesh, B;Banavali, Shripad D;Badwe, Rajendra A;Ramesh, C;Appaji, Lingappa;Nandakumar, Ambakumar 4193
Background: Globally, retinoblastoma is the most common primary intraocular malignancy occurring in children. This paper documents the recent incidence rates of retinoblastoma by age and sex groups from the Population Based Cancer Registries (PBCRs) of Bangalore, Mumbai, Chennai, Delhi and Kolkata using the data from the National Cancer Registry Programme. Materials and Methods: Relative proportions, sex ratio, method of diagnosis, and incidence rates (crude and age standardized) for each PBCR and pooled rates of the five PBCRs were calculated for the years 2005/06 to 2009/10. Standard errors and 95% confidence limits of ASIRs by sex group in each PBCR were calculated using the Poisson distribution. Standardised rate ratios of ASIR by sex group and rate ratios at risk were also calculated. Results: The maximum retinoblastoma cases were in the 0-4 age group, accounting for 78% (females) and 81% (males) of pooled cases from five PBCRs. The pooled crude incidence rate in the 0-14 age group was 3.5 and the pooled ASIR was 4.4 per million. The pooled ASIR in the 0-4, 5-9 and 10-14 age group were 9.6, 2.0 and 0.1 respectively. The M/F ratio in Chennai (1.9) and Bangalore PBCRs (2.0) was much higher than the other PBCRs. Among the PBCRs, the highest incidence rate in 0-4 age group was found in males in Chennai (21.7 per million), and females in Kolkata (18.9 per million). There was a distinct variation in incidence rates in the PBCRs in different geographic regions of India. -
Karamese, Murat;Aydogdu, Sabiha;Karamese, Selina Aksak;Altoparlak, Ulku;Gundogdu, Cemal 4199
Background: Hepatitis B virus infection is one of the major world health problems. Epigallocatechin-3 gallate is the major component of the polyphenolic fraction of green tea and it has an anti-viral, anti-mutagenic, anti-tumorigenic, anti-angiogenic, anti-proliferative, and/or pro-apoptotic effects on mammalian cells. In this study, our aim was to investigate the inhibition of HBV replication by epigallocatechin-3 gallate in the Hep3B2.1-7 hepatocellular carcinoma cell line. Materials and Methods: HBV-replicating Hep3B2.1-7 cells were used to investigate the preventive effects of epigallocatechin-3 gallate on HBV DNA replication. The expression levels of HBsAg and HBeAg were determined using ELISA. Quantitative real-time-PCR was applied for the determination of the expression level of HBV DNA. Results: Cytotoxicity of epigallocathechin-3-gallate was not observed in the hepatic carcinoma cell line when the dose was lower than$100{\mu}M$ . The ELISA method demonstrated that epigallocatechin-3 gallate have strong effects on HBsAg and HBeAg levels. Also it was detected by real-time PCR that epigallocatechin-3 gallate could prevent HBV DNA replication. Conclusions: The obtained data pointed out that although the exact mechanism of HBV DNA replication and related diseases remains unclear, epigallocatechin-3 gallate has a potential as an effective anti-HBV agent with low toxicity. -
Wang, Jian-Jun;Wang, Ze-You;Chen, Rui;Xiong, Jing;Yao, Yong-Liang;Wu, Jian-Hong;Li, Guang-Xin 4203
Exosomes, membranous nanovesicles, naturally carry bio-macromolecules or miRNA and play impoetant roles in tumor pathogenesis. Here, we showed that macrophages cell-derived exosomes can function as vehicles to deliver exogenous miR-21 inhibitor into BGC-823 gastric cancer cells. Exosomes loaded with miR-21inhibitor significantly increased miR-21 levels in BGC-823, but miR-21inhibitor loaded in exosomes exerted an opposite effect. miRNA transfected with exosomes had less cellular toxicity to host cells compared to conventional transfection methods. The miR-21inhibitor loaded exosomes promoted the migration ability and reduced apoptosis of BGC-823 gastric cancer cells. These observations indicate that miR-21 acts as a tumor promoter by targeting the PDCD4 gene and preventing apoptosis of gastric cancer cells through inhibition of PDCD4 expression. Furthermore, exosome -mediated miR-21 inhibitor delivery resulted in functionally more efficient inhibition and less cellular toxicity compared to conventional transfection methods. Similar approaches could be useful in modification of target biomolecules in vitro and in vivo. These findings contribute to our understanding of the functions of miR-21 and exosomes as a carrier for therapy of gastric cancer. -
Background: Prognostic value of prophylactic level VII nodal dissection in papillary thyroid carcinoma has been highlighted. Materials and Methods: A total of 27 patients with papillary thyroid carcinoma with N0 neck underwent total thyroidectomy with level VI and VII nodal dissection through same collar neck incision. Multicentricity, bilaterality, extrathyroidal extension, level VI and VII lymph nodes were studied as separate and independent prognostic factors for DFS at 24 months. Results: 21 females and 6 males with a mean age of 34.6 years old, tumor size was 5-24 mm. (mean 12.4 mm.), multicentricity in 11 patients 2-4 foci (mean 2.7), bilaterality in 8 patients and extrathyroidal extension in 8 patients. Dissected level VI LNs 2-8 (mean 5 LNs) and level VII LNs 1-4 (mean 1.9). Metastatic level VI LNs 0-3 (mean 1) and level VII LNs 0-2 (mean 0.5). Follow-up from 6-51 months (mean 25.6) with 7 patients showed recurrence (3 local and 4 distant). Cumulative DFS at 24 months was 87.8% and was significantly affected in relation to bilaterality (p-value <0.001), extrathyroidal extension (p-value <0.001), level VI positive ((p-value <0.001) and level VII positive ((p-value <0.001) LNs. No recurrences were detected during the follow-up period in the absence of level VI and level VII nodal involvement. Conclusions: Level VII prophylactic nodal dissection is an important and integral prognostic factor in papillary thyroid carcinoma. A larger multicenter study is crucial to reach a satisfactory conclusion about the necessity and safety of this approach.
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Farahani, Roya Kishani;Azimzadeh, Pedram;Rostami, Elham;Malekpour, Habib;Aghdae, Hamid Asadzadeh;Pourhoseingholi, Mohamad Amin;Mojarad, Ehsan Nazemalhosseini;Zali, Mohammad Reza 4215
Gastric cancer (GC) is one of the most common malignancies in the world. It is the first cause of cancer deaths in both sexes In Iranian population. Circulating insulin-like growth factor-one (IGF-1) levels have been associated for gastric cancer. IGF-1 protein has central roles involved in the regulation of epithelial cell growth, proliferation, transformation, apoptosis and metastasis. Single nucleotide polymorphism in IGF-1 regulatory elements may lead to alter in IGF-1expression level and GC susceptibility. The aim of this study was to investigate the influence of IGF-1 gene polymorphism (rs5742612) on risk of GC and clinicopathological features for the first time in Iranian population. In total, 241 subjects including 100 patients with GC and 141 healthy controls were recruited in our study. Genotypes were analyzed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay with DNA from peripheral blood. The polymorphism was statistically analyzed to investigate the relationship with the risk of GC and clinicopathological properties. Logistic regression analysis revealed that there was no significant association between rs5742612 and the risk of GC. In addition, no significant association between genotypes and clinicopathological features was observed (p value>0.05). The frequencies of the CC, CT, and TT genotypes were 97%, 3%, and 0%, respectively, among the cases, and 97.9%, 2.1%, and 0%, respectively, among the controls. CC genotype was more frequent in cases and controls. The frequencies of C and T alleles were 98.9% and 1.1% in controls and 98.5% and 1.5% in patient respectively. Our results provide the first evidence that this variant is rare in Iranian population and it may not be a powerful genetic predisposing biomarker for prediction GC clinicopathological features in an Iranian population. -
Goklu, Mehmet Rifat;Seckin, Kerem Doga;Togrul, Cihan;Goklu, Yasemin;Tahaoglu, Ali Emre;Oz, Murat;Ertas, Ibrahim Egemen 4219
Background: Hydronephrosis is frequently encountered in advanced stage cervical cancers, and may be associated with mortality. In the present study, we aimed to demonstrate the effect of hydronephrosis on survival in patients with inoperable advanced stage cervical cancer. Materials and Methods: The study data were acquired by retrospective analysis of the patient records belonging to 165 women with FIGO (International Federation of Gynecology and Obstetrics) stage-IIIB or more advanced cervical cancer, which were not surgical candidates. Parameters including patient age, pathological diagnosis, disease stage, pelvic sidewall extension, presence of hydronephrosis and administration of chemoradiation were analyzed. Further, the effects of these variables on survival were assessed. P values less than 0.05 were considered statistically significant. Results: The distribution of the study patients according to disease stage was as follows: 131 (79.4%) had stage-IIIB, 18 (10.9%) had stage-IVB and 16 (% 9.7) patients had stage-IVA disease. Hydronephrosis was not evident in 91 (55.2%) of these patients, whereas 41 (24.8%) had unilateral and 33 (20%) patients had bilateral hydronephrosis. When compared to mean survival in patients who did not have hydronephrosis, survival was significantly shortened in patients who had bilateral and unilateral hydronephrosis (p<0.05). There was no significant survival difference between patients with unilateral and bilateral hydronephrosis (p>0.05). Although patient age, pathological type, pelvic involvement, and chemotherapy treatment rates were similar (p>0.05), radiotherapy requirement rate and disease stage were significantly different among the study groups (p<0.05). Conclusions: Hydronephrosis was found to be a significant predictor of poor survival in patients with advanced stage cervical cancer, irrespective of unilateral or bilateral involvement.While waiting for future studies with larger sample sizes, we believe that the FIGO stages in advanced cervical cancer could further be stratified into subgroups according to presence or absence of hydronephrosis. -
Zhao, Jian;Zhang, Xi;Chen, Rui;Zhao, Yu-Qian;Wang, Ting-Ting;He, Shan;Qiao, You-Lin 4223
Objective: To investigate the diagnostic value of the R-way colposcopic evaluation system (R-way system) in cervical cancer screening. Materials and Methods: Between August 2013 and August 2014, a total of 1,059 cases referred to colposcopy in Peking University First Hospital were studied using both the R-way system and conventional colposcopy. Our study evaluated and compared the diagnostic ability of the two methods in detecting high-grade lesions and cervical cancer (hereinafter called CIN2+). Evaluation indicators including sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), Youden index and the area under the curve (AUC) of the receiver operating characteristic (ROC) were calculated. Results: The R-way system had a slightly lower specificity (94.5%) than conventional colposcopy (96.0%) for CIN2+ detection (P=0.181). However, the sensitivity (77.8%) was significantly higher than with the conventional colposcopic method (46.6%) (${\chi}^2=64.351$ , P<0.001). In addition, the AUC of the ROC for CIN2+ detection using the R-way system (0.839) was larger than that with conventional colposcopy (0.731) (Z=4.348, P<0.001). If preliminary result had been drawn from cervical exfoliated cytology before colposcopy referral, combination of the R-way system with cytology could increase the sensitivity to 93.9% for CIN2+ detection (excluding ASCUS\LSIL), confirmed by multipoint biopsy or ECC. Conclusions: The diagnostic value of the R-way evaluation system is higher than that of conventional colposcopic evaluation in cervical cancer screening. Moreover, taking the ease of use and standardized quality control management into account, the R-way system is highly preferable. -
Omran, Suha;Barakat, Husam;Muliira, Joshua Kanaabi;Bashaireh, Ibrahim;Batiha, Abdul-Moni'm 4229
Background: Colorectal cancer (CRC is increasingly becoming a major cause of cancer morbidity and mortality in Jordan. However the population's level of awareness about CRC, CRC screening test preferences and willingness to embrace screening are not known. The aim of this study was to assess the level of CRC awareness and screening preferences among Jordanian patients. Materials and Methods: A survey assessing the CRC knowledge levels was distributed among patients attending outpatient gastroenterology clinics in public hospitals throughout Jordan. A total of 800 surveys were distributed and of these 713 (89.1%) were returned. Results: Only 22% of the participants correctly judged CRC among the choices provided as the commonest cause of cancer related deaths. The majority of participants (68.3%) underestimated their risk for CRC. Only 26.8% correctly judged their life time risk while 5% overestimated their risk. Two thirds of participants (66%) were willing to pay 500 Jordanian Dinars (equivalent to 706 US$) in order to get a prompt colonoscopy if recommended by their physician, while 25.5% reported that they would rather wait for 6 months in order to get a free colonoscopy. Conclusions: Although the participants tended to underestimate their risk for CRC, they were mostly aware of CRC as a major cause of mortality and were willing to embrace the concept of CRC screening and bear the related financial costs. These findings about CRC awareness and propensity for screening provide a good foundation as the Jordanian health system moves forward with initiatives to promote CRC screening and prevention. -
Dubey, Ashutosh Kumar;Gupta, Umesh;Jain, Sonal 4237
Breast cancer is a menacing cancer, primarily affecting women. Continuous research is going on for detecting breast cancer in the early stage as the possibility of cure in early stages is bright. There are two main objectives of this current study, first establish statistics for breast cancer and second to find methodologies which can be helpful in the early stage detection of the breast cancer based on previous studies. The breast cancer statistics for incidence and mortality of the UK, US, India and Egypt were considered for this study. The finding of this study proved that the overall mortality rates of the UK and US have been improved because of awareness, improved medical technology and screening, but in case of India and Egypt the condition is less positive because of lack of awareness. The methodological findings of this study suggest a combined framework based on data mining and evolutionary algorithms. It provides a strong bridge in improving the classification and detection accuracy of breast cancer data. -
Ilker, Selcuk;Nilufer, Cetinkaya;Firat, Cuylan Zeliha;Bulent, Ozdal;Hatice, Bayramoglu;Tayfun, Gungor 4247
Objective: To determine the predictors of lympho-vascular space invasion (LVSI) in endometrial cancers which contain mucinous carcinomatous histology. Materials and Methods: Clinical and histopathological data of endometrial carcinomas with a mucinous carcinomatous component diagnosed between January 2007 and January 2014 at the Gynecologic Oncology Department of Zekai Tahir Burak Women's Health Education and Research Hospital were reviewed retrospectively. Results: Twelve patients (25.5%) were positive for LVSI and 35 (74.5%) patients were negative. Patients with LVSI were mostly staged higher than 1A. Mean age, BMI and parity were not significantly different between patient groups. Larger tumor diameter (${\geq}2cm$ ) (p=0.04) and elevated Ca125 and Ca-19.9 (p=0.01) levels were significant for predicting LVSI. We also found>1/2 myometrial invasion (p<0.001), cervical stromal involvement (p=0.002) and higher grade (2-3) (p=0.001) significant for predicting LVSI. In multivariate analysis we found only grade significant for predicting LVSI. Conclusions: Especially grade of tumor is a crucial factor for determining LVSI in endometrial cancers with mucinous carcinomatous components. -
Xing, Yong-Hua;Zhang, Jun-Ling;Lu, Lu;Li, De-Guan;Wang, Yue-Ying;Huang, Song;Li, Cheng-Cheng;Zhang, Zhu-Bo;Li, Jian-Guo;Xu, Guo-Shun;Meng, Ai-Min 4251
Background: Exposure to cigarette may affect human health and increase risk of a wide range of diseases including pulmonary diseases, such as chronic obstructive pulmonary disease (COPD), asthma, lung fibrosis and lung cancer. However, the molecular mechanisms of pathogenesis induced by cigarettes still remain obscure even with extensive studies. With systemic view, we attempted to identify the specific gene modules that might relate to injury caused by cigarette smoke and identify hub genes for potential therapeutic targets or biomarkers from specific gene modules. Materials and Methods: The dataset GSE18344 was downloaded from the Gene Expression Omnibus (GEO) and divided into mouse cigarette smoke exposure and control groups. Subsequently, weighted gene co-expression network analysis (WGCNA) was used to construct a gene co-expression network for each group and detected specific gene modules of cigarette smoke exposure by comparison. Results: A total of ten specific gene modules were identified only in the cigarette smoke exposure group but not in the control group. Seven hub genes were identified as well, including Fip1l1, Anp32a, Acsl4, Evl, Sdc1, Arap3 and Cd52. Conclusions: Specific gene modules may provide better understanding of molecular mechanisms, and hub genes are potential candidates of therapeutic targets that may possible improve development of novel treatment approaches. -
Ilker, Selcuk;Elmas, Korkmaz;Emre, Ozgu;Mengu, Turker;Erkaya, Salim;Tayfun, Gungor 4257
Background: Uterine papillary serous tumors are rarely seen and behave aggressively. Our aim was to evaluate uterine papillary serous tumors arising from polyps. Materials and Methods: Clinicopathological data of patients with uterine serous cancer arising from a polyp at the Gynecological Oncology Department of Zekai Tahir Burak Women's Health Education and Research Hospital were reviewed retrospectively. Results: We analyzed patients according to FIGO 2009 staging system as stage 1A and higher than stage 1A (3 and 6, respectively). All the patients were postmenopausal. Mean CA-125, CA-19.9 and CA15.3 levels were elevated in higher than stage 1A group. However we did not find a statistical difference between age, parity, polyp size, CA-125, CA-15.3, CA-19.9 and CEA levels. Lympho-vascular space invasion (LVSI) showed predictivity for advanced disease (p=0.025). Conclusions: The histopathologic nature of uterine serous carcinoma is a unique entity. LVSI is a prognosticator for defining an advanced stage uterine papillary tumor. -
Gul, Asiye;Ustundag, Hulya;Andsoy, Isil Isik;Kalkanli, Suheyla 4261
The aim of the study was to evaluate the level of anxiety and pain in women with breast cancer. Patients who had been treated with modified radical mastectomy or breast conserving surgery were included. Data were gathered using the state-trait anxiety inventory and the visual analog scale. The pain levels and analgesic consumption of the patients were evaluated after surgery. The study sample consisted of 150 women. The mean age of the participants was$50.54{\pm}10.02$ . Most of the patients (58%) received breast conserving surgery. The mean state anxiety score was$44.74{\pm}11.91$ , and the mean trait anxiety score was$48.78{\pm}9.48$ before surgery. The mean pain level on the first day following surgery was$3.26{\pm}1.91$ and analgesic consumption was$2.98{\pm}1.08$ . There was no correlation between patient pain and anxiety levels. There was very slightly positive correlation between trait anxiety and total analgesic consumption. Assessing the levels of anxiety in breast cancer patients before surgery may contribute to the determination of postoperative pain. -
Gundogan, Fatih Cakir;Yolcu, Umit;Tas, Ahmet;Sahin, Omer Faruk;Uzun, Salih;Cermik, Hakan;Ozaydin, Sukru;Ilhan, Abdullah;Altun, Salih;Ozturk, Mustafa;Sahin, Fahri;Erdem, Uzeyir 4265
Introduction: The aim of the study was to explore the distribution of eyelid tumors in Ankara, the capital city of Turkey, from a histopathological point of view. Materials and Methods: Medical records of 1,502 patients who had eyelid surgery because of tumoral lesions were retrospectively reviewed after obtaining institutional review board approval. A total of 1,541 lesions with histopathologic diagnosis were included. Inflammatory tumoral lesions were excluded. The lesions were categorized into three groups according to the origin: epidermal, adnexal tumors and 'others', including melanocytic, neural and vascular lesions. Results: Of the total of 1,541, 908 lesions were epidermal in origin. Only 22 (1.5%) were malignant, and 6.0% was premalignant lesions such as actinic keratosis and Bowen's disease. Twenty-one of 22 malignant lesions were basal cell carcinoma. There was only one patient with squamous cell carcinoma and no sebaceous cell carcinoma. Among the benign tumors (92.5%), squamous papilloma was the most frequent (21.8% of all lesions). The other frequent lesions were nevus (17.6%), seborrheic keratosis (17.3%), hydrocystomas (10.6%), xanthelasma (7.6%) and epidermal cysts (7.2%). Conclusions: The results of this study are in accordance with published literature. The absence of sebaceous cell carcinomas needs to be stressed. -
Yu, Jian-Qin;Zhou, Qing;Zheng, Yun-Fei;Bao, Ying 4271
Objectives: To investigate the expression of vimentin and Ki-67 proteins in cervical squamous cell carcinoma (CSCC) and their relationships with patient clinicopathological features. Materials and Methods:Fifty-seven CSCC samples archived in Department of Pathology in the First Affiliated Hospital of Wenzhou Medical University were selected. The expression of vimentin and Ki-67 proteins in CSCC tissue were detected using immunohistochemical SP method, and correlations between them and their relationships with clinicopathological features were analyzed. Results: Among 57 CSCC tissues, there were 43 with positive expression of Vimentin, and the positive rate was 75.4%; there were 57 cases with positive expression of Ki-67, and the positive rate came up to 100.0%. The results of Pearson correlation analysis displayed that the expression of vimentin had a significantly-positive correlation with Ki-67 in CSCC tissue (r=0.984, co0.000). The expression of both Ki-67 and vimentin was intimately associated with the presence or absence of local invasion and lymph node metastasis as well as differentiated degrees of the tumor (P=0.003, 0.017, 0.000; P=0.001, 0.008, 0.003) instead of the age, tumor size and clinical staging (P>0.05). Conclusions: Epithelial-mesenchymal transition (EMT) tends to appear in poorly-differentiated CSCC tissue, and the up-regulation of vimentin expression is accompanied by high expression of Ki-67, suggesting that invasion and metastasis readily occur in these tumor cells. -
Limtrakul, Pornngarm;Yodkeeree, Supachai;Pitchakarn, Pornsiri;Punfa, Wanisa 4277
Anthocyanin, a phenolic compound, has been reported to have an anti-inflammatory effect against lipopolysaccharide (LPS) induced changes in immune cells. However, little is known about the molecular mechanisms underlying its anti-inflammatory effects. Few research studies have concerned the anti-inflammation properties of colored rice extract as a functional material. Therefore, the purpose of this study was to examine anti-inflammatory effects of the polar fraction of black rice whole grain extracts (BR-WG-P) that features a high anthocyanin content. Our results showed that BR-WG-P significantly inhibited LPS-induced pro-inflammatory mediators, including production of NO and expression of iNOS and COX-2. In addition, secretion of pro-inflammatory cytokines including TNF-${\alpha}$ and IL-6 was also significantly inhibited. Moreover, BR-WG-P and anthocyanin inhibited NF-kB and AP-1 translocation into the nucleus. BR-WG-P also decreased the phosphorylation of ERK, p38 and JNK in a dose dependent manner. These results suggested that BR-WG-P might suppress LPS-induced inflammation via the inhibition of the MAPK signaling pathway leading to decrease of NF-kB and AP-1 translocation. All of these results indicate that BR-WG-P exhibits therapeutic potential associated with the anthocyanin content in the extract for treating inflammatory diseases associated with cancer. -
Thakur, Priyanka;Seam, Rajeev Kumar;Gupta, Manoj Kumar;Rastogi, Madhup;Gupta, Manish;Bhattacharyya, Tapesh;Sharma, Mukesh;Revannasiddaiah, Swaroop 4285
Purpose: Blood hemoglobin levels are known to influence response to radiotherapy. This retrospective analysis compared the effect of hemoglobin levels upon response to radiation among patients treated with radiation alone (by accelerated hyperfractionated radiotherapy) versus those treated with concurrent cisplatin chemoradiotherapy. Materials and Methods: Among patients treated for locally advanced carcinoma of the cervix (LACC) during 2009-10, a total of 60 fulfilled the eligibility criteria. In this time frame, external beam radiotherapy was delivered with either concurrent chemoradiotherapy (CRT, n=31) (45Gy over 25 fractions, with weekly cisplatin at 40mg/m2), or with accelerated hyperfractionated radiotherapy (AHRT, n=29) (20Gy over 10 daily fractions over the first two weeks, followed by 30Gy over 20 fractions over the next two weeks, with two fractions of 1.5Gy per day, without the use of chemotherapy). Mean weekly hemoglobin (MWH) levels of all patients were calculated as the arithmetic means of weekly recorded blood hemoglobin levels. As per MWH, patients in both of the AHRT or the CRT groups were classified into two subgroups-those with MWH between 10-10.9g/dL, or with MWH>11g/dL. Complete response (CR) to external beam RT phase (prior to brachytherapy) was declared after clinical examinations and computed tomography. The CR rate was noted for both MWH sub-groups within each of the AHRT and CRT groups. Results: Within the AHRT group, patients with MWH>11g/dL had a much better CR rate in comparison to those with MWH:10-10.9g/dL (80% vs. 21.1%) which was statistically significant (p 0.0045). Within the CRT group, there was no significant difference in the outcomes within the MWH>11g/dL and MWH:10-10.9g/dL sub-groups (CR rates of 80% vs. 61.9%, p=0.4285). Conclusions: The importance of maintaining a minimum hemoglobin level of 11g/dL during RT is much greater for patients treated with RT alone, than for patients treated with concurrent chemoradiotherapy. Enhanced haemoglobin levels during RT may to an extent negate the ill-effects that may otherwise arise due to non-use of concurrent chemotherapy. -
Sambyal, Vasudha;Manjari, Mridu;Sudan, Meena;Uppal, Manjit Singh;Singh, Neeti Rajan;Singh, Harpreet;Guleria, Kamlesh 4291
Background: Chemokines and their receptors influence carcinogenesis and cysteine-cysteine chemokine receptor 5 (CCR5) directs spread of cancer to other tissues. A 32 base pair deletion in the coding region of CCR5 that might alter the expression or function of the protein has been implicated in a variety of immune-mediated diseases. The action of antiviral drugs being proposed as adjuvant therapy in cancer is dependent on CCR5 wild type status. In the present study, distribution of CCR5${\Delta}32$ polymorphism was assessed in North Indian esophageal cancer patients to explore the potential of using chemokine receptors antagonists as adjuvant therapy. Materials and Methods: DNA samples of 175 sporadic esophageal cancer patients (69 males and 106 females) and 175 unrelated healthy control individuals (69 males and 106 females) were screened for the CCR5${\Delta}32$ polymorphism by direct polymerase chain reaction (PCR). Results: The frequencies of wild type homozygous (CCR5/CCR5), heterozygous (CCR5/${\Delta}32$ ) and homozygous mutant (${\Delta}32/{\Delta}32$ ) genotypes were 96.0 vs 97.72%, 4.0 vs 1.71% and 0 vs 0.57% in patients and controls respectively. There was no difference in the genotype and allele frequencies of CCR5${\Delta}32$ polymorphism in esophageal cancer patients and control group. Conclusions: The CCR5${\Delta}32$ polymorphism is not associated with esophageal cancer in North Indians. As the majority of patients express the wild type allele, there is potential of using antiviral drug therapy as adjuvant therapy. -
Mo, Ling-Zhao;Song, Hong-Lin;Wang, Jian-Li;He, Qing;Qiu, Zhang-Can;Li, Fei 4297
Background: To evaluate HPV testing by Hybrid Capture II (HCII) in conjunction with cytology in detecting the residual/recurrence disease after treatment of high-grade cervical intraepithelial neoplasia (CIN II-III) with loop electrosurgical excision procedure (LEEP). Materials and Methods: A retrospective review of 158 patients with histologically confirmed CIN II-III who underwent LEEP between January 2011 and October 2012 was conducted. Post-treatment control was scheduled at the 3rd, 6th, 12th and 18th month. All patients were followed up by Pap smear and HR-HPV genotype and viral load testing. Results: Pre-treatment, HR-HPV DNA, was detected in all specimens of the patients. At follow-up, 25 patients were diagnosed as the residual/recurrent disease during the FU visit, among whom, 16 patients with positive margin: 13 patients (52%) with HR-HPV DNA+/cytology+, 2 patients (8%) with HR-HPV DNA+/cytology-, 1 patient (4%) with cytology+/HR-HPV DNA-; 9 patients with clean margin - 5 patients (55.6%) with HR-HPV DNA+/cytology+; 2 patients (22.2%) with HRHPV DNA+/cytology-, 2 patients (22.2%) with cytology+/HR-HPV DNA-. None of them persisting HR-HPV DNA-/cytology-with positive or negative margin was identified as the residual/recurrent disease. The majority of residual/recurrent disease was detected at the 12th and 18th month FU, and there was almost no difference in the sensitivity and negative predictive value (NPV) between at the 3rd month and the 6th month FU visits. 14 residual/recurrence disease (14/46:30.4%) had pre-treatment high viral load (>5 000 RUL/PC) and 11 (11/112, 9.8%) with pre-treatment low viral load, P<0.05. Conclusions: (1) The persistence HR-HPV DNA is the root cause of the residual/recurrent disease for the women treated for high-grade CIN; the pre-treatment viral load and margin can be seen as the predictor. (2) The FU visit beginning at the 6th month post-treatment and lasting at least 24 months with the combination of cytology and HPV testing. (3) Patients with high pre-treatment HPV load, which is considered as one risk of developing the residual/recurrent disease, should be paid more attention (especially above 500RUL/PC) to by clinicians. -
Shahat, Abdelaaty A;Alsaid, Mansour S;Kotob, Soheir E;Ahmed, Hanaa H 4303
Rumex vesicarius is an edible herb distributed in Egypt and Saudi Arabia. The whole plant has significant value in folk medicine and it has been used to alleviate several diseases. Hepatocellular carcinoma (HCC), the major primary malignant tumor of the liver, is one of the most life-threatening human cancers. The goal of the current study was to explore the potent role of Rumex vesicarius extract against HCC induced in rats. Thirty adult male albino rats were divided into 3 groups: (I): Healthy animals received orally 0.9 % normal saline and served as negative control group, (II): HCC group in which rats were orally administered N-nitrosodiethylamine NDEA, (III): HCC group treated orally with R. vesicarius extract in a dose of 400 mg/kg b.wt daily for two months. ALT and AST, ALP and${\gamma}$ -GT activities were estimated. CEA, AFP, AFU, GPC-3, Gp-73 and VEGF levels were quantified. Histopathological examination of liver tissue sections was also carried out. The results of the current study showed that the treatment of the HCC group with R. vesicarius extract reversed the significant increase in liver enzymes activity, CEA, AFP, AFU, glypican 3, golgi 73 and VEGF levels in serum as compared to HCC-untreated counterparts. In addition, the favorable impact of R. vesicarius treatment was evidenced by the marked improvement in the histopathological features of the liver of the treated group. In conclusion, the present experimental setting provided evidence for the significance of R. vesicarius as anticancer candidate with a promising anticancer potential against HCC. The powerful hepatoprotective properties, the potent antiangiogenic activity and the effective antiproliferative capacity are responsible for the anticancer effect of this plant. -
Andas, A Reenaa Joys;Abdul, Ahmad Bustamam;Rahman, Heshu Sulaiman;Sukari, Mohd Aspollah;Abdelwahab, Siddig Ibrahim;Samad, Nozlena Abdul;Anasamy, Theebaa;Arbab, Ismail Adam 4311
Hepatocellular carcinoma (HCC) is a primary liver cancer with high global incidence and mortality rates. Current candidate drugs to treat HCC remain lacking and those in use possess undesirable side effects. In this investigation, the antiproliferative effects of dentatin (DTN), a natural coumarin, were evaluated on HepG2 cells and DTN's probable preliminary molecular mechanisms in apoptosis induction were further investigated. DTN significantly (p<0.05) suppressed proliferation of HepG2 cells with an$IC_{50}$ value of$12.0{\mu}g/mL$ , without affecting human normal liver cells, WRL-68 ($IC_{50}$ >$50{\mu}g/mL$ ) causing$G_0/G_1$ cell cycle arrest via apoptosis induction. Caspase colorimetric assays showed markedly increased levels of caspase-3 and caspase-9 activities throughout the treatment period. Western blotting of treated HepG2 cells revealed inhibition of$NF-{\kappa}B$ that triggers the mitochondrial-mediated apoptotic signaling pathway by up-regulating cytoplasmic cytochrome c and Bax, and down-regulating Bcl-2 and Bcl-xL. The current findings suggest DTN has the potential to be developed further as an anticancer compound targeting human HCC. -
El Nemr Esmail, Reham Shehab;El Farouk Abdel-Salam, Lubna Omer;Abd El Ellah, Mohammed M 4317
Background: Prognostic biomarkers in breast cancer are routinely investigated in the primary tumors to guide further management. However, it is proposed that the expression may change during the disease progression, and may result in a different immune profile in the metastatic nodes. This work aimed to investigate the expression of breast prognostic biomarkers in primary tumors and in its axillary nodal metastasis, to estimate the possible discordant expression. Materials and Methods: 60 paired primary and axillary nodal metastasis samples were collected from patients with primary breast cancer with positive nodal deposits, diagnosed at the Maadi Military Hospital, Cairo, Egypt, during the year 2013. ER, PR and HER2 expression was assessed by immunohistochemistry in all samples Results: 48.3% of the included cases showed concordant results for both ER and PR receptors between the primary tumor and its nodal metastasis while 51.7% showed discordant results and the discordance level was statistically significant. On the other hand, 70% of the cases showed concordant Her2 results between the primary tumors and the nodal deposits, 30% showed discordant results and the difference was significant. Conclusions: The study indicated that the discordance in ER and PR receptor expression between the primary breast tumor and their nodal metastasis may be significant. The possible switch in the biomarker status during the disease progression is worth noting and may change the patient therapeutic planning. So, whether the treatment selection should be based on biomarkers in the lymph node is a topic for further studies and future clinical trials. -
Onur, Gulcin Ozkan;Tarcan, Ercument;Onur, Asim;Can, Huseyin;Atahan, Murat Kemal;Yigit, Seyran Ceri;Cakalagaoglu, Fulya 4323
Background: Breast cancer is the most common cause of deaths of cancer in women. Nowadays, following completion of imaging methods, mainly fine needle aspiration biopsy (FNAB) and core biopsy methods have been used for establishing cytopathological diagnosis although discussions regarding superiority continue. Materials and Methods: Those with a complaint of "mass in breast" along with those diagnosed to have a mass as a result of routine physical examination among all patients applying to our clinic between 01.01.2009 and 31.12.2011 were retrospectively assessed. Totals of 146 and 64 patients with complete radiological observation who had undergone FNAB and core biopsies, respectively, were evaluated. Postoperative pathological results of patients of both groups receiving surgery were also taken into consideration. All results were compared in terms of false positivity/negativity, sensitivity/specifity, surgery types and distribution of postoperative results with regard to diagnoses along with those of malignant/benign masses with regard to quadrants determined. Results: Diagnostic malignancy power of mammographic BIRADS classification was 87.3%. However, the value was 75% in the core biopsy group. Sensitivity and specifity following comparison of FNAB and postoperative pathology results of those receiving surgery were 85.4% and 92.9% while they were 93.5% and 100% in the core biopsy group. Diagnostic malignancy power, calculated by determining AUC in ROC analysis, of FNAB was 89.1% while that of core biopsy was 96.7%. Conclusions: It was shown that core biopsy is superior to FNAB in terms of sensitivity, specificity and accurate histopathological classification. However; quick, cheap and basic diagnosis by means of FNAB should not be ignored. Sensitivity of FNAB is rather high in experienced hands and furthermore it would be expected to be lower than with core biopsy. -
Huang, Xiang;Guan, Dan;Shu, Yong-Qian;Liu, Lian-Ke;Ni, Fang 4329
Background: To investigate the change of frequency and immuno-inhibitory function of myeloid-derived suppressor cells (MDSCs) after treatment of cisplatin (DDP) in A375 human melanoma model. Materials and Methods: BALB/c nude mice were inoculated with A375 cells to establish the human melanoma model and randomly divided into control group given normal saline (NS) and experimental group treated with DDP (5 mg/kg). The percentages of MDSCs in the tumor tissue and peripheral blood after DDP treatment were detected by flow cytometry. The proliferation and interferon-${\gamma}$ (IFN-${\gamma}$ ) secretion of T cells co-cultured with MDSCs were analyzed through carboxyfluorescein succinimidyl ester (CFSE) labeling assay and enzyme-linked immunospot (ELISPOT) assay, respectively. Results: In A375 human melanoma model, DDP treatment could significantly decrease the percentage of MDSCs in the tumor tissue, but exerted no effect on the level of MDSCs in peripheral blood. Moreover, DDP treatment could attenuate the immuno-inhibitory function of MDSCs. T cells co-cultured with DDP-treated MDSCs could dramatically elevate the proliferation and production of INF-${\gamma}$ . Conclusions: DDP can decrease the frequency and attenuate immuno-inhibitory function of MDSCs in A375 melanoma model, suggesting a potential strategy to augment the efficacy of combined immunotherapy. -
Quadri, Mir Faeq Ali;Alharbi, Fahd;Bajonaid, Amal Mansoor S;Moafa, Ibtisam Hussain Y;Sharwani, Abubakker Al;Alamir, Abdulwahab Hussain A 4335
Background: Oral cancer is the third most common malignancy in Saudi Arabia, the highest incidence of which is reported from Jazan province. The objective of this study was to evaluate the association of various locally used substances, especially shamma, with oral cancer in the Jazan region of Saudi Arabia. Materials and Methods: A hospital-based case-control study was designed and patient records were scanned for histologically confirmed oral cancer cases. Forty eight patients who were recently diagnosed with oral cancer were selected as cases. Two healthy controls were selected for each observed case and they were matched with age (+/- 5 years) gender and location. Use of different forms of tobacco such as cigarettes, pipe-smoking and shamma (smokeless-tobacco) was assessed. Khat, a commonly used chewing substance in the community was also included. Descriptive analysis was first performed followed by multiple logistic regression (with and without interaction) to derive odds ratios (ORs) and 95% confidence interval (CIs). Results: Mean age of the study sample (56% males and 44% females) was 65.3 years. Multinomial regression analysis revealed that shamma use increased the odds of developing oral cancer by 29 times (OR=29.3; 10.3-83.1). Cigarette (OR=6.74; 2.18-20.8) was also seen to have an effect. With the interaction model the odds ratio increased significantly for shamma users (OR=37.2; 12.3-113.2) and cigarette smokers (OR=10.5; 2.88-3.11). Khat was observed to have negative effect on the disease occurrence when used along with shamma (OR=0.01; 0.00 - 0.65). Conclusions: We conclude that shamma, a moist form of smokeless tobacco is a major threat for oral cancer occurrence in the Jazan region of Saudi Arabia. This study gives a direction to conduct further longitudinal studies in the region with increased sample size representing the population in order to provide more substantial evidence. -
Ekpanyaskul, Chatchai;Sangrajrang, Suleeporn;Ekburanawat, Wiwat;Brennan, Paul;Mannetje, Andrea;Thetkathuek, Anamai;Saejiw, Nutjaree;Ruangsuwan, Tassanu;Boffetta, Paolo 4339
Occupational exposure to wood dust is one cause of nasopharyngeal cancer (NPC); however, assessing this exposure remains problematic. Therefore, the objective of this study was to develop a semi-quantitative exposure assessment method and then utilize it to evaluate the association between occupational exposure to wood dust and the development of NPC. In addition, variations in risk by histology were examined. A case-control study was conducted with 327 newly diagnosed cases of NPC at the National Cancer Institute and regional cancer centers in Thailand with 1:1 controls matched for age, gender and geographical residence. Occupational information was obtained through personal interviews. The potential probability, frequency and intensity of exposure to wood dust were assessed on a job-by-job basis by experienced experts. Analysis was performed by conditional logistic regression and presented in odds ratio (ORs) estimates and 95% confidence intervals (CI). Overall, a non significant relationship between occupational wood dust exposure and NPC risk for all subjects was observed (ORs=1.61, 95%CI 0.99-2.59); however, the risk became significant when analyses focused on types 2 and 3 of NPC (ORs=1.62, 95%CI 1.03-2.74). The significant association was stronger for those exposed to wood dust for > 10 year (ORs=2.26, 95%CI 1.10-4.63), for those with first-time exposure at age > 25 year (ORs=2.07, 95%CI 1.08-3.94), and for those who had a high cumulative exposure (ORs=2.17, 95%CI 1.03-4.58) when compared with those considered unexposed. In conclusion, wood dust is likely to be associated with an increased risk of type 2 or 3 NPC in the Thai population. The results of this study show that semi-quantitative exposure assessment is suitable for occupational exposure assessment in a case control study and complements the information from self-reporting. -
Yuan, Zhi-Jun;Zhou, Wen-Wu;Liu, Wei;Wu, Bai-Ping;Zhao, Jin;Wu, Wei;He, Yi;Yang, Shuo;Su, Jing;Luo, Yi 4347
Background: Previous studies showed that genetic polymorphisms of glutathione S-transferase P1 (GSTP1) were involved in glutathione metabolism and genetic polymorphisms of ribonucleotide reductase (RRM1) were correlated with DNA synthesis. Here we explored the effects of these polymorphisms on the chemosensitivity and clinical outcome in Chinese non-small cell lung cancer (NSCLC) patients treated with gemcitabine-cisplatin regimens. Materials and Methods: DNA sequencing was used to evaluate genetic polymorphisms of GSTP1 Ile105Val and RRM1 C37A-T524C in 47 NSCLC patients treated with gemcitabine-cisplatin regimens. Clinical response was evaluated according to RECIST criteria after 2 cycles of chemotherapy and toxicity was assessed by 1979 WHO criteria (acute and subacute toxicity graduation criteria in chemotherapeutic agents). Results: There was no statistical significance between sensitive and non-sensitive groups regarding the genotype frequency distribution of GSTP1 Ile105Val polymorphism (p>0.05). But for RRM1 C37A-T524C genotype, sensitive group had higher proportion of high effective genotype than non-sensitive group (p=0.009). And according to the joint detection of GSTP1 Ile105Val and RRM1 C37A-T524C polymorphisms, the proportion of type A (A/A + high effective genotype) was significantly higher in sensitive group than in non-sensitive group (p=0.009). Toxicity showed no correlation with the genotypes between two groups (p>0.05). Conclusions: Compared with single detection of genetic polymorphisms of GSTP1 Ile105Val or RRM1 C37A-T524C, joint detection of both may be more helpful for patients with NSCLC to receive gemcitabine-cisplatin regimens as the first-line chemotherapy. Especially, genetic polymorphism of RRM1 is more likely to be used as an important biomarker to predict the response and toxicity of gemcitabine-cisplatin combination chemotherapy in NSCLC. -
Prapitpaiboon, Hatainuch;Mahachai, Varocha;Vilaichone, Ratha-Korn 4353
Background: Levofloxacin is an effective medication for second line Helicobacter pylori (H. pylori) eradication. However, limited studies have approved its use as an effective antibiotic in first line therapy. Dexlansoprazole is a new PPI and lacks of evidence in support of a role in H. pylori eradication. This study was designed to evaluate efficacy of levofloxacin-dexlansoprazole-based quadruple therapy for H. pylori eradication in Thailand. Materials and Methods: This prospective randomized control study was performed during June 2014 to December 2014. H. pylori infected gastritis patients were randomized to receive 7- or 14-day levofloxacin-dexlansoprazole based on quadruple therapy (levofloxacin 500 mg OD, dexlansoprazole 60 mg bid, clarithromycin MR 1000 mg OD, bismuth subsalicylate 1048 mg bid). CYP2C19 genotyping and antibiotic susceptibility tests were conducted for all patients. A 13C urea breath test was performed to confirm H. pylori eradication at least 4 weeks after treatment. Results: A total of 100 patients were enrolled, comprising 44 males and 56 females (mean age of 52.6 years). Eradication rate by PP analysis was 85.7% (42/49) with the 7-day regimen and 98% (48/49) with the 14-day regimen (85.7% vs 98%; p-value=0.059). ITT analysis was 84% and 96% with 7- and 14-day regimens, respectively (84% vs 96%; p-value=0.092). Antibiotic susceptibility testing demonstrated 35.1% resistance to metronidazole, 18.3% to clarithromycin, and 13.5% to levofloxacin. CYP2C19 genotyping revealed 54.1% RM, 34.7% IM and 11.2% PM. The 14-day regimen provided 100% eradication in patients with clarithromycin or dual clarithromycin and metronidazole H. pylori resistant strains. Moreover, the eradication rate was 96.6% in patients with CYP2C19 genotype RM. Conclusions: The 14-day levofloxacin-dexlansoprazole based quadruple therapy provides high H. pylori eradication regardless of CYP2C19 genotype, clarithromycin or dual clarithromycin and metronidazole resistant strains. This regimen could be use as an alternative first line therapy for H. pylori eradication in Thailand. -
Jetawattana, Suwimol;Boonsirichai, Kanokporn;Charoen, Savapong;Martin, Sean M 4357
Thunbergia Laurifolia Linn. (TL) is one of the most familiar plants in Thai traditional medicine that is used to treat various conditions, including cancer. However, the antitumor activity of TL or its constituents has never been reported at the molecular level to support the folklore claim. The present study was designed to investigate the antitumor effect of an aqueous extract of TL in human breast cancer cells and the possible mechanism(s) of action. An aqueous crude extract was prepared from dried leaves of TL. Folin-Ciocalteu colorimetric assays were used to determine the total phenolic content. Antiproliferative and cell cycle effects were evaluated in human breast adenocarcinoma MCF-7 cells by MTT reduction assay, cell growth inhibition, clonogenic cell survival, and flow cytometric analysis. Free radical generation by the extracts was detected using electron paramagnetic resonance spectroscopy. The exposure of human breast adenocarcinoma MCF-7 cells to a TL aqueous extract resulted in decreases in cell growth, clonogenic cell survival, and cell viability in a concentration-dependent manner with an$IC_{50}$ value of$843{\mu}g/ml$ . Treatments with extract for 24h at$250{\mu}g/ml$ or higher induced cell cycle arrest as indicated by a significant increase of cell population in the G1 phase and a significant decrease in the S phase of the cell cycle. The capability of the aqueous extract to generate radical intermediates was observed at both high pH and near-neutral pH conditions. The findings suggest the antitumor bioactivities of TL against selected breast cancer cells may be due to induction of a G1 cell cycle arrest. Cytotoxicity and cell cycle perturbation that are associated with a high concentration of the extract could be in part explained by the total phenolic contents in the extract and the capacity to generate radical intermediates to modulate cellular proliferative signals. -
Pongsuvareeyakul, Tip;Khunamornpong, Surapan;Settakorn, Jongkolnee;Sukpan, Kornkanok;Suprasert, Prapaporn;Intaraphet, Suthida;Siriaunkgul, Sumalee 4363
Background: The tumor-stroma ratio (TSR) represents the percentage of neoplastic cell components compared to the combined area of neoplastic cells and the surrounding tumor-induced stroma. A low TSR (predomination of stromal component) has been demonstrated to be an independent adverse prognostic factor in cancers of several organs. In cervical carcinoma patients, TSR has been evaluated in only one previous study with different histological types. The present study aimed to assess the prognostic value of TSR in early stage cervical cancer patients with adenocarcinoma histology only. Materials and Methods: Histological slides of patients with early stage (IB-IIA) cervical adenocarcinoma who underwent surgical treatment between January 2003 and December 2011 were reviewed. Patients who had received preoperative chemotherapy were excluded. TSR was categorized as low (<50%) and high (${\geq}50%$ ). Correlations between TSR and clinicopathological variables were evaluated. Prognostic values of TSR and other variables were estimated using Cox's regression. Results: Of 131 patients; 38 (29.0%) had low TSR and 93 (71.0%) had high TSR. The patients with low TSR had significantly higher proportions of deep cervical stromal invasion (outer third of wall, p=0.011; residual stroma less than 3 mm, p=0.008) and parametrial involvement (p=0.026). Compared to the patients with high TSR, those with low TSR tended to have lower 5-year disease-free survival rate (83.8% versus 88.9%) and overall survival rate (85.6% versus 90.3%), although the differences were not statistically significant. Low TSR was significantly associated with decreased overall survival in univariate analysis (HR 2.7; 95% CI 1.0-7.0; p=0.041), but not in multivariate analysis. TSR was not significantly associated with decreased disease-free survival. Conclusions: Low TSR is associated with decreased overall survival in patients with early stage cervical adenocarcinoma treated by surgery. However, it was not found to be an independent prognostic predictor in this study. -
Wu, Wei;Xia, Qing;Luo, Rui-Jie;Lin, Zi-Qi;Xue, Ping 4369
Background: To investigate in-vitro antagonistic effect of low-dose liquiritigenin on gemcitabine-induced capillary leak syndrome (CLS) in pancreatic adenocarcinoma via inhibiting reactive oxygen species (ROS)-mediated signalling pathways. Materials and Methods: Human pancreatic adenocarcinoma Panc-1 cells and human umbilical vein endothelial cells (HUVECs) were pre-treated using low-dose liquiritigenin for 24 h, then added into gemcitabine and incubated for 48 h. Cell viability, apoptosis rate and ROS levels of Panc-1 cells and HUVECs were respectively detected through methylthiazolyldiphenyl-tetrazoliumbromide (MTT) and flow cytometry. For HUVECs, transendothelial electrical resistance (TEER) and transcellular and paracellular leak were measured using transwell assays, then poly (ADP-ribose) polymerase 1 (PARP-1) and metal matrix proteinase-9 (MMP9) activity were assayed via kits, mRNA expressions of p53 and Rac-1 were determined through quantitative polymerase chain reaction (qPCR); The expressions of intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and PARP-1 were measured via western blotting. Results: Low-dose liquiritigenin exerted no effect on gemcitabine-induced changes of cell viability, apoptosis rate and ROS levels in Panc-1 cells, but for HUVECs, liquiritigenin ($3{\mu}M$ ) could remarkably elevate gemcitabine-induced decrease of cell viability, transepithelial electrical resistance (TEER), pro-MMP9 level and expression of ICAM-1 and VCAM-1 (p<0.01). Meanwhile, it could also significantly decrease gemcitabine-induced increase of transcellular and paracellular leak, ROS level, PARP-1 activity, Act-MMP9 level, mRNA expressions of p53 and Rac-1, expression of PARP-1 and apoptosis rate (p<0.01). Conclusions: Low-dose liquiritigenin exerts an antagonistic effect on gemcitabine-induced leak across HUVECs via inhibiting ROS-mediated signalling pathways, but without affecting gemcitabine-induced Panc-1 cell apoptosis. Therefore, low-dose liquiritigenin might be beneficial to prevent the occurrence of gemcitabine-induced CLS in pancreatic adenocarcinoma. -
Yerci, Omer;Sehitoglu, Ibrahim;Ugras, Nesrin;Cubukcu, Erdem;Yuce, Suleyman;Bedir, Recep;Cure, Erkan 4377
Background: Gastroenteropancreatic neuroendocrine tumors (GNs) are slow growing and although their incidence has increased in recent years, they are relatively rarely seen. Somatostatin analogues are used in the treatment of GNs that express somatostatin receptor (SR). We aimed to investigate the expression of SR2 and SR5 in GNs. Materials and Methods: In this study the expression of SR2 and SR5 was investigated immunohistochemically in 49 cases (26 males, 23 females) diagnosed and graded with GN according to the World Health Organization classification 2010. Results: The percentage of SR2 staining was 91.0% in grade 1, 82.8% in grade 2 and 100% in grade 3. On the other hand, the percentage of SR5 staining was 81.8% % in grade 1, 60.0% in grade 2 and 0% in grade 3. According to the tumor localization, the percentages of SR2 expression were as follows: pancreas 85.7%, stomach 100%, small bowel 70%, appendix 85.7% and rectum 100%. The percentages of SR5 expression were: pancreas 61,9%, stomach 37.5%, small bowel 70%, appendix 71.5% and rectum 66.6%. There was a significant negative correlation between ki67 percentage and SR5 expression (r=-0.341, p=0.016). Conclusions: In this study, GNs were found to highly express SR2 and SR5. Although the expression of SR2 and SR5 changed according to tumor localization, the expression of SR2 was higher than the expression of SR5 in GN. There was a significant negative correlation between ki67 and SR5. Accordingly, SR5 may be a prognostic indicator of GN. -
Choi, Jeong-Hwa;Yates, Zoe;Martin, Charlotte;Boyd, Lyndell;Ng, Xiaowei;Skinner, Virginia;Wai, Ron;Kim, Jeongseon;Woo, Hae Dong;Veysey, Martin;Lucock, Mark 4383
Background: The C1561T variant of the glutamate carboxypeptidase II (GCPII) gene is critical for natural methylfolylpolyglutamte (methylfolate) absorption, and has been associated with perturbations in folate metabolism and disease susceptibility. However, little is known on C1561T-GCPII as a risk factor for colorectal cancer. Therefore, this study examined whether C1561T-GCPII influences folate metabolism and adenomatous polyp occurrence. Materials and Methods: 164 controls and 38 adenomatous polyp cases were analysed to determine blood folate and plasma homocysteine (Hcy) level, dietary intake of natural methylfolate, synthetic pteroylglutamic acid (PteGlu), vitamin C and C1561T-GCPII genotype. Results: In controls and cases, 7.3 and 18.4 percent of subjects respectively, were found to have the CT genotype, increasing the risk for adenomatous polyp occurrence 2.86 times (95% CI:1.37-8.0, p=0.035). Total dietary folate, methylfolate and PteGlu intake and the level of erythrocyte folate and plasma Hcy did not predict the occurrence of an adenomatous polyp. However, dietary natural vitamin C intake was associated with adenomatous polyp risk within C1561T-GCPII CT genotype subjects (p=0.037). Conclusions: The findings suggest that C1561T-GCPII variation may be associated with risk for adenomatous polyp, and vitamin C may modify risk by interacting with the variant gene, its expression product and/or folate substrates. -
Alikanoglu, Arsenal Sezgin;Gunduz, Seyda;Demirpence, Ozlem;Suren, Dinc;Gunduz, Umut Riza;Sezer, Cem;Yildiz, Mustafa;Yildirim, Mustafa 4387
Background: Tight junctions (TJs) organise paracellular permeability and they have an important role in epithelial and endothelial cell polarity and permanence of barrier function. It has been demonstrated that the Claudin family constitutes an important component of them. In this study, we assessed expression patterns of of Claudin1, 4 and 7 and whether they have any relation with prognosis in patients with pancreatic cancer. Materials and Methods: Expression patterns of Claudin 1,4 and 7 were examined by immunohistochemistry in 25 patients with a histopathological diagnosis of pancreatic cancer using a semiquantitative scoring of the extent and intensity of staining. After grouping the staining scores as low (final score 0-2) and high (final score 3-9) the relation between expression of Claudin 1,4 and 7 and survival was evaluated. Results: There was no significant relation between expression of Claudin 1,4 and 7 and gender and stage. No statistically significant relation was found between Claudin 1 and 4 expression and survival whereas a statistically significant relation was found between decrease in Claudin 7 expression and decrease in survival. Conclusions: Claudins have important functions other than their popular function known as adhesion. Supporting this hypothesis, we found a statistically significant relationship between increased Claudin 7 expression and increased survival time, and this suggests that Claudin 7 may exert different tumorigenic effects in pancreatic cancer other than its well-known adhesion effect. -
Zheng, Wei;Xu, Yuan-Ji;Qiu, Su-Fang;Zong, Jing-Feng;Huang, Ling-Ling;Huang, Chao-Bin;Lin, Shao-Jun;Pan, Jian-Ji 4393
Background: To explore the independent prognostic factors for the recurrence/metastasis of patients with locoregionally advanced nasopharyngeal carcinoma (LANPC). Materials and Methods: A total of 604 patients initially diagnosed as LANPC by pathohistology in Fujian Provincial Cancer Hospital were selected to analyze the relationship between the clinical pathological patterns, therapeutic protocols and clinical stages with the recurrence/metastasis of LANPC. Results: The 1-, 3- and 5-year locoregionally recurrent rates of LANPC patients were 2.0%, 9.5% and 12.9% respectively, with average recurrent period being 78 months. Univariate analysis results indicated that clinical stages had certain influence on the recurrent period of LANPC patients. However, COX regression models showed that ages, genders and clinical stages were not the independent prognostic factors influencing the recurrence. The 1-, 3- and 5-year metastatic rates of LANPC patients were 6.6%, 17.5% and 18.8% respectively, with average metastatic period of 73 months. Univariate analysis results demonstrated that ages, N stages, clinical stages, locations of lymph node, retropharyngeal lymph node and extracapsular invasion of lymph node had certain influence on the metastatic period of LANPC patients. Additionally, further COX regression analysis results suggested that T stages, reduction protocols and extracapsular invasion of lymph node were the independent prognostic factors influencing the metastasis of patients with LANPC, in which T stages and extracapsular invasion of lymph node were the pestilent factors while reduction protocols the protective factor. Conclusions: Induction chemotherapy is beneficial to LANPC patients with initial treatment, and the metastatic rate decreases greatly after the application of reduction chemotherapy. -
Jongudomkarn, D;Singhawara, P;Macduff, C 4401
Background: Cancer is a primary source of concern in Thailand and other countries around the world, including the Asian-Pacific region. Evidence supports that an important contributing cause of cancer and other chronic illnesses such as stroke, diabetes, and hypertension is excessive alcohol consumption. Studies conducted in Thailand reveal a worrisome rise in the number of new and regular drinkers in communities. Therefore, actions for primary, secondary and tertiary prevention of problem drinking are necessary. In recent years nurses in North East Thailand have been developing and implementing the Khon Kaen Family Health Nursing model to embed disease prevention in communities through the actions of family health nurses and local family health leaders. Aim: The aim of this qualitative research was to better understand the experiences of the local family health leaders using this model and to synthesize lessons learned. Materials and Methods: As part of a participatory action research approach involving analysis of focus group discussions and individual interviews, the experiences of 45 family health leaders were synthesized. Results: Four main themes were identified, namely: i) Family first: role modeling beginning at the personal and family level. ii) Local leverage: using village community forums to reduce alcohol drinking. iii) Gentle growth: making the first step and treading gently; and iv) Respect, Redemption, Rehabilitation: valuing the person to re-integrate them in the village society. Conclusions: As alcohol consumption in the village declined significantly following the prevention program, these findings illuminate how low-tech integrated prevention approaches may be very useful, particularly in rural communities. The lessons learned may have relevance not only in Thailand but in other countries seeking to prevent and mitigate behavior that conduces to diseases such as cancer. -
Senthilkumar, Chinnu Sugavanam;Akhter, Sameena;Malla, Tahir Mohiuddin;Sah, Nand Kishore;Ganesh, Narayanan 4409
The Bhopal gas tragedy involving methyl isocyanate (MIC) is one of the most horrific industrial accidents in recent decades. We investigated the genotoxic effects of MIC in long-term survivors and their offspring born after the 1984 occurrence. There are a few cytogenetic reports showing genetic damage in the MIC-exposed survivors, but there is no information about the associated cancer risk. The same is true about offspring. For the first time, we here assessed the micronucleus (MN) frequency using cytokinesis-blocked micronucleus (CBMN) assay to predict cancer risk in the MIC-affected population of Bhopal. A total of 92 healthy volunteers (46 MIC-affected and 46 controls) from Bhopal and various regions of India were studied taking gender and age into consideration. Binucleated lymphocytes with micronuclei (BNMN), total number of micronuclei in lymphocytes (MNL), and nuclear division index (NDI) frequencies and their relationship to age, gender and several lifestyle variabilities (smoking, alcohol consumption and tobacco-chewing) were investigated. Our observations showed relatively higher BNMN and MNL (P<0.05) in the MIC-affected than in the controls. Exposed females (EF) exhibited significantly higher BNMN and MNL (P<0.01) than their unexposed counterparts. Similarly, female offspring of the exposed (FOE) also suffered higher BNMN and MNL (P<0.05) than in controls. A significant reduction in NDI (P<0.05) was found only in EF. The affected group of non-smokers and non-alcoholics featured a higher frequency of BNMN and MNL than the control group of non-smokers and non-alcoholics (P<0.01). Similarly, the affected group of tobacco chewers showed significantly higher BNMN and MNL (P<0.001) than the non-chewers. Amongst the affected, smoking and alcohol consumption were not associated with statistically significant differences in BNMN, MNL and NDI. Nevertheless, tobacco-chewing had a preponderant effect with respect to MNL. A reasonable correlation between MNL and lifestyle habits (smoking, alcohol consumption and tobacco-chewing) was observed only in the controls. Our results suggest that EF and FOE are more susceptible to cancer development, as compared to EM and MOE. The genotoxic outcome detected in FOE reflects their parental exposure to MIC. Briefly, the observed cytogenetic damage to the MIC-affected could contribute to cancer risk, especially in the EF and FOE. -
An, Song-Lin;Xiao, Ting;Wang, Li-Ming;Rong, Wei-Qi;Wu, Fan;Feng, Li;Liu, Fa-Qiang;Tian, Fei;Wu, Jian-Xiong 4421
Objectives: To investigate the prognosis significance of preoperative serum alpha-fetoprotein (AFP) and the correlation with clinicopathological factors of hepatocellular carcinoma (HCC) patients who underwent hepatectomy. Materials and Methods: Clinicopathological data of retrospective analysis were collected for 251 HCC patients undergoing hepatectomy in this study. According to preoperative AFP level, patients were categorized into AFP-negative (0-20ng/mL) and AFP-positive (>20 ng/mL) groups for Kaplan-Meier analysis and Cox proportional hazard regression modeling. Results: The results demonstrated that increased AFP was associated with longer prothrombin time (PTs), liver capsule invasion, low grade differentiation, and late Barcelona Clinic Liver Center (BCLC) stage. Moreover, the female patients had a greater prevalence of increased preoperative AFP than male patients [284.8 (3.975-3167.5) vs (3.653-140.65); Z-2.895, p=0.004]. The 1-, 3-, and 5-year recurrence-free survival (RFS) rates were 78.1, 57.5, and 40.6 % in the AFP-negative group and 61.8, 37.7, and 31.4 %, respectively, in the AFP-positive group (log-rank test 8.312, p=0.004). The 1-, 3-, and 5-year overall survival (OS) rates were 94.4, 83.8, and 62.3% in the AFP-negative group and 87.2, 60.0, and 36.7%, respectively, in the AFP-positive group. The difference was statistically significant (log-rank test, 16.884, p=0.000). Cox proportional-hazards model identified preoperative AFP to be an independent prognostic predictor of overall survival. Conclusions: Preoperative serum AFP is an independent predictor of prognosis among HCC patients following surgical resection. Female patients have a higher preoperative AFP than their male counterparts. -
Formosa, Joseph;Jenner, Rachel;Nguyen-Thi, My-Duyen;Stephens, Caitlin;Wilson, Corey;Ariyawardana, Anura 4429
Background: Public awareness/knowledge on oral and pharyngeal cancer (OPC), potentially malignant disorders (PMODs) and their risk factors is crucial for prevention and early detection of OPC and PMODs. Yet, there are no published data available on the awareness and knowledge of OPC and PMODs among people living in Far North Queensland, Australia. Materials and Methods: This study was conducted as a cross sectional survey. A self-administered questionnaire was designed and consisted of relevant questions to ascertain socio-demographic information, awareness and knowledge of OPC, PMODs and risk factors and questions on participant's exposure to risk factors and dietary history were also included. Survey was carried out at the Dental Clinic of the James Cook University School of Dentistry (JCU Dental), Cairns, Australia. Subjects above the age of 20 years (n=366) were randomly selected during the period from 31st July to 6th September 2013 and questionnaire was distributed to complete while they are waiting for treatment. Data analysis was carried out using SPSS version 21 and the chi -squared test was employed to compare groups. P<0.05 was considered statistically significant. Results: The study revealed that 52.3% of the respondents were aware of the existence of OPC but only 19.0% were aware of PMODs. Of those who were aware of oral cancer, 92% agreed or strongly agreed that smoking is a strong risk factor for OPC. Similarly a relatively high proportion of the respondents agreed or strongly agreed that tobacco chewing (84%), tobacco chewing with areca nut (68%), chewing areca nut alone (51%) and exposure to actinic radiation (71%) as risk factors. However, the results for alcohol intake, age, and HPV infection were found to be relatively poor with proportions 33%, 34%, and 23% respectively. Conclusions: This study revealed an alarming lack of awareness and knowledge of OPC and PMODs. -
Huang, Yong-Sheng;Fan, Qian-Qian;Li, Chuang;Nie, Meng;Quan, Hong-Yang;Wang, Lin 4435
p21 is a cyclin-dependent kinase inhibitor, which can arrest cell proliferation and serve as a tumor suppressor. Though many studies were published to assess the relationship between p21 rs1059234 polymorphism and various cancer risks, there was no definite conclusion on this association. To derive a more precise quantitative assessment of the relationship, a large scale meta-analysis of 5,963 cases and 8,405 controls from 16 eligible published case-control studies was performed. Our analysis suggested that rs1059234 was not associated with the integral cancer risk for both dominant model [(T/T+C/T) vs C/C, OR=1.00, 95% CI: 0.84-1.18] and recessive model [T/T vs (C/C+C/T), OR=1.03, 95% CI: 0.93-1.15)]. However, further stratified analysis showed rs1059234 was greatly associated with the risk of squamous cell carcinoma of head and neck (SCCHN). Thus, larger scale primary studies are still required to further evaluate the interaction of p21 rs1059234 polymorphism and cancer risk in specific cancer subtypes. -
Ying, Min;Zhu, Xiao-Xia;Zhao, Yang;Li, Dian-He;Chen, Long-Hua 4439
Background: Because there is no clear consensus for the prognostic implication of KRAS mutations in patients with non-small cell lung cancer (NSCLC), we conducted a meta-analysis based on 12 randomized trials to draw a more accurate conclusion. Materials and Methods: A systematic computer search of articles from inception to May 1, 2014 using the PubMed, EMBASE, and Cochrane databases was conducted. The enrollment of articles and extraction of data were independently performed by two authors. Results: Our analysis was based on the endpoints overall survival (OS) and progression-free survival (PFS). Nine records (All for OS, 7 for PFS) comprising 12 randomized trials were identified with 3701 patients who underwent a test for KRAS mutations. In the analysis of the pooled hazard ratios (HRs) for OS (HR: 1.39; 95% confidence interval [CI] 1.23-1.56) and PFS (HR: 1.33; 95% CI 1.17-1.51), we found that KRAS mutations are related to poor survival benefit for NSCLC. According to a subgroup analysis stratified by disease stage and line of therapy, the combined HRs for OS and PFS coincided with the finding that the presence of a KRAS mutation is a dismal prognostic factor. However, the prognostic role of KRAS mutations are not statistically significant in a subgroup analysis of patients treated with chemotherapy in combination with cetuximab based on the endpoints OS (P=0.141) and PFS (P=0.643). Conclusions: Our results indicate that KRAS mutations are associated with inferior survival benefits for NSCLC but not for those treated with chemotherapies integrating cetuximab. -
Safavi, Ali;Raad, Nasim;Raad, Neda;Ghorbani, Jahangir 4447
Background: Nasopharyngeal cancer is a disease with distinct ethnic and geographical distribution. The aim of this review was to describe the epidemiological characteristics of nasopharyngeal cancer in Iran from 2004 to 2009 because no systematic study has been performed to evaluate the trends of its incidence yet. Materials and Methods: The data were derived from the databases of the National Cancer Data System Registry in the period of 2004-2009. Nasopharyngeal cancers were classified according to the International Classification of Diseases for Oncology. Incidence rates and trends were calculated and evaluated by gender, age decade, and histopathology types. Results: A total of 1,637 nasopharyngeal cancers were registered in Iran from 2004 to 2009 giving an incidence of 0.38 per 100,000. The male-to-female ratio was 2.08:1. The trend of incidence was found to have increased, with a significant increase observed in males. Undifferentiated carcinoma was the most common histopathology type in all the age decades. Conclusions: Because the incidence of nasopharyngeal cancers in Iran has increased, especially in males, further studies are recommended for understanding of the etiological factors involved in the rise of the disease. -
Background: The aim of our present study was to compare quality of life (QoL) between intermediate-stage (BCLC-B) HCC patients who had undergone either liver resection or transcatheter arterial chemoembolization (TACE). Materials and Methods: A total of 102 intermediate-stage HCC patients participated in our study, including 58 who had undergone liver resection and 44 who had undergone TACE. Baseline demographic characteristics, tumor characteristics, and long-term outcomes, such as tumor recurrence, were compared and analyzed. QoL was assessed using the Short Form (SF)-36 health survey questionnaire with the mental and physical component scales (SF-36 MCS and PCS). This questionnaire was filled out at HCC diagnosis and 1, 3, 6, 12, 24 months after surgery. Results: For the preoperative QoL evaluation, the 8 domains related to QoL were comparable between the two groups. The PCS and MCS scores were significantly decreased in both the TACE and resection groups at1 month after surgery, and this decrease was greater in the resection group. These scores were significantly lower in the resection group compared with the TACE group (P<0.05). However, these differences disappeared at 3 and 6 months following surgery. One year after surgery, the resection group showed much higher PCS scores than the TACE patients (P=0.018), and at 2 years after surgery, the PCS and MCS scores for the resection group were significantly higher than those for the TACE group (P<0.05). Eleven patients (19.0%) in the resection group and 17 (38.6%) in the TACE group suffered HCC recurrence (P<0.05). Univariate and multivariate analyses indicated that tumor recurrence (HR=1.211, 95%CI: 1.086-1.415, P=0.012) was a significant risk factor for poorpostoperative QoL in the HCC patients.Conclusions: Due to its effects on reducing HCC recurrence and improving long-term QoL, liver resection should be the first choice for the treatment of patients with intermediate-stage HCC.
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Zhang, Meng;Xiong, Hu;Fang, Lu;Lu, Wei;Wu, Xun;Huang, Zhan-Sen;Wang, Yong-Qiang;Cai, Zhi-Ming;Wu, Song 4457
Common genetic variation Q192R in the paraoxonase 1 (PON1) gene has been considered to be implicated in the development of many cancers. Nevertheless, results from the related studies were inconsistent. To elucidate the association, we performed a meta-analysis for 8,112 cases and 10,037 controls from 32 published case-control studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the association by STATA 12.0 software. Overall, we revealed that the PON1-192R allele was associated with a reduced risk of the overall cancers. Moreover, in the stratified analysis by cancer types (breast cancer, prostate cancer, brain cancer etc.), the results showed that PON1-192R allele was associated with a decreased risk in breast cancer (R vs Q: OR=0.605, 95% CI=0.378-0.967,$P_{heterogeneity}=0.000$ ; RR vs QQ: OR=0.494, 95% CI=0.275-0.888,$P_{heterogeneity}=0.002$ ; RQ vs QQ: OR=0.465, 95% CI=0.259-0.835,$P_{heterogeneity}=0.000$ ; and RR+RQ vs QQ: OR=0.485, 95% CI=0.274-0.857,$P_{heterogeneity}=0.000$ ), and associated with prostate cancer in homozygote (RR vs QQ: OR=0.475, 95% CI=0.251-0.897,$P_{heterogeneity}=0.001$ ) and recessive models (RR vs RQ+QQ: OR=0.379, 95% CI=0.169-0.853,$P_{heterogeneity}=0.000$ ), while an increased risk was identified in lymphoma (R vs Q: OR=1.537, 95% CI=1.246-1.896,$P_{heterogeneity}=0.944$ ; RR vs QQ: OR=2.987, 95% CI=1.861-4.795,$P_{heterogeneity}=0.350$ ; RR+RQ vs QQ: OR=1.354, 95% CI=1.021-1.796,$P_{heterogeneity}=0.824$ ; and RR vs RQ+QQ: OR=2.934, 95% CI=1.869-4.605,$P_{heterogeneity}=0.433$ ), and an increased risk in prostate cancer under heterozygote comparison (RQ vs QQ: OR=1.782, 95% CI=1.077-2.950,$P_{heterogeneity}=0.000$ ) and dominant models (RR+RQ vs QQ: OR=1.281, 95% CI=1.044-1.573,$P_{heterogeneity}=0.056$ ). When subgroup analysis that performed by the control source (hospital based or population based), a decreased risk of the overall cancers was revealed by homozygote (RR vs QQ: OR=0.601, 95% CI=0.366-0.987,$P_{heterogeneity}=0.000$ ) and dominant models (RR vs RQ+QQ: OR= 0.611, 95% CI=0.384-0.973,$P_{heterogeneity}=0.000$ ) in hospital based group. Stratifying by ethnicity, a significantly reduced risk of the overall cancers under allele contrast model (R vs Q: OR=0.788, 95% CI=0.626-0.993,$P_{heterogeneity}=0.000$ ) was uncovered in Caucasian. In summary, these findings suggested that PON1 Q192R polymorphism was associated with a reduced risk of the overall cancers, nevertheless, it might increase cancer susceptibility of prostate and lymphoma risk. Large well-designed epidemiological studies will be continued on this issue of interest. -
Background: As the third generation of platinum-based antineoplastic agent aginst gastrointestinal cancer, oxaliplatin is considered to be associated with severe sensory neurotoxicity. Acorrding to previous studies, vitaminE, intravenous Ca/Mg and glutamine may partly reduce the incidence and severity of oxaliplatin-induced neurotoxicity. The aim of this study was to investigate the safety and efficacy of analgecine for preventing oxaliplatin-induced neurotoxicity in the patients with gastrointestinal tumors. Method: In this study, patients undergoing oxaliplatin-based chemotherapy were assigned to analgecine (experimental) group or control group. Analgecine 6ml was administered once a day for seven days from the day of oxaliplatin treatment. The National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE; version 3) was used to evaluate oxaliplatin-induced neurotoxicity. The incidence rates and grade of neurotoxicity of patients were assessed before and during (after four and eight cycles) treatment. Results: Totally, 82 patients were enrolled in this study, 42 in experimental group and 40 in control group. The occurrence of each grade neurotoxicity in the experimental group was significantly lower than that in control group. The overall occurrence rate was 31% vs 55% (P=0.043) after 4 cycles and 52% vs 75% (P=0.050) after 8 cycles. Conclusion: Analgecine appears could be effective in reducing oxaliplatin-induced neurotoxicity and be applicated for patients with gastrointestinal tumors who would be treated with oxaliplatin-based chemotherapy.
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Lin, Chang-Ming;Ma, Ji-Min;Zhang, Li;Hao, Zong-Yao;Zhou, Jun;Zhou, Zhen-Yu;Shi, Hao-Qiang;Zhang, Yi-Fei;Shao, En-Ming;Liang, Chao-Zhao 4469
Transient receptor potential melastain 7 (TRPM7) is a bifunctional protein with dual structure of both ion channel and protein kinase, participating in a wide variety of diseases including cancer. Recent researches have reported the mechanism of TRPM7 in human cancers. However, the correlation between TRPM7 and prostate cancer (PCa) has not been well studied. The objective of this study was to investigate the potential the role of TRPM7 in the apoptosis of PC-3 cells, which is the key cell of advanced metastatic PCa. In this study, we demonstrated the influence and potential function of TRPM7 on the PC-3 cells apoptosis induced by TNF-related apoptosis inducing-ligand (TRAIL). The study also found a novel up-regulated expression of TRPM7 in PC-3 cells after treating with TRAIL. Suppression of TRPM7 by TRPM7 non-specific inhibitors ($Gd^{3+}$ or 2-aminoethoxy diphenylborate (2-APB) ) not only markedly eliminated TRPM7 expression level, but also increased the apoptosis of TRAIL-treated PC-3 cells, which may be regulated by the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway accompany with up-regulated expression of cleaved Caspase-3, (TRAIL-receptor 1, death receptors 4) DR4, and (TRAIL-receptor 2, death receptors 5) DR5. Taken together, our findings strongly suggested that TRPM7 was involved in the apoptosis of PC-3 cells induced by TRAIL, indicating that TRPM7 may be applied as a therapeutic target for PCa.