Asian Pacific Journal of Cancer Prevention
Asian Pacific Organization for Cancer Prevention (아시아태평양암예방학회)
Health Sciences > Development of Pharmaceutical
The Asian Pacific Journal of Cancer Prevention is a monthly electronic journal publishing papers in all areas of cancer control. Its is indexed on PubMed (Impact factor for 2014 : 2.514) and the scope is wide-ranging: including descriptive, analytical and molecular epidemiology; experimental and clinical histopathology/biology of preneoplasias and early neoplasias; assessment of risk and beneficial factors; experimental and clinical trials of primary preventive measures/agents; screening approaches and secondary prevention; clinical epidemiology; and all aspects of cancer prevention education. All of the papers published are freely available as pdf files downloadable from www.apjcpcontrol.org, directly or through PubMed, or obtainable from the first authors. The APJCP is financially supported by the UICC Asian Regional Office and the National Cancer Center of Korea, where the Editorial Office is housed.
KSCI
Volume 18 Issue 11
Volume 17 Issue sup3
The mTOR Signalling Pathway in Cancer and the Potential mTOR Inhibitory Activities of Natural Phytochemicals
Tan, Heng Kean;Moad, Ahmed Ismail Hassan;Tan, Mei Lan 6463
https://doi.org/10.7314/APJCP.2014.15.16.6463 PDF KSCI
The mammalian target of rapamycin (mTOR) kinase plays an important role in regulating cell growth and cell cycle progression in response to cellular signals. It is a key regulator of cell proliferation and many upstream activators and downstream effectors of mTOR are known to be deregulated in various types of cancers. Since the mTOR signalling pathway is commonly activated in human cancers, many researchers are actively developing inhibitors that target key components in the pathway and some of these drugs are already on the market. Numerous preclinical investigations have also suggested that some herbs and natural phytochemicals, such as curcumin, resveratrol, timosaponin III, gallic acid, diosgenin, pomegranate, epigallocatechin gallate (EGCC), genistein and 3,3'-diindolylmethane inhibit the mTOR pathway either directly or indirectly. Some of these natural compounds are also in the clinical trial stage. In this review, the potential anti-cancer and chemopreventive activities and the current status of clinical trials of these phytochemicals are discussed.
Smokeless Tobacco (Shammah) in Saudi Arabia: A Review of its Pattern of Use, Prevalence, and Potential Role in Oral Cancer
Alsanosy, Rashad Mohammed 6477
Background: Shammah is a traditional form of chewing tobacco [smokeless tobacco, (ST)] that is commonly used in the Middle East especially in Saudi Arabia (KSA), Yemen and Sudan. The Substance Abuse Research Centre (SARC) at Jazan University noted that no adequate research and information on the prevalence of shammah use in the province of Jazan, and KSA as well, has been provided in the scientific literature. Materials and Methods: An intensive systematic review of online databases was performed, including AMED (The Allied and Complementary Medicine Database), Biological Abstracts, Cochrane Collection Plus, Dentistry and Oral Sciences Source, E-Journals Database, EBSCO Discovery Service, MEDLINE, PEMSoft, PEP Archive, PsycARTICLES, scopus, Sciencedirect and Google Scholar. Results: Shammah is a mixture of powdered tobacco, lime, ash, black pepper, oils and flavorings. ST in KSA is placed in the buccal or lower labial vestibule of the mouth. The user (or dipper) spits out insoluble debris. The importation of ST products is prohibited in KSA. Accessible information on legislative action to control the use of ST in KSA appeared in 1990. The actual percentage use may be higher, than reported since shammah is illegal in KSA and there may be some reluctance to admit to its use. Conclusions: This review paper is an initial step in a funded research project by SARC to understand the pattern of use of shammah and provide adequate epidemiological data. One goal of this review is to generate further data for public health education.
Recently Emerging Signaling Landscape of Ataxia-Telangiectasia Mutated (ATM) Kinase
Farooqi, Ammad Ahmad;Attar, Rukset;Arslan, Belkis Atasever;Romero, Mirna Azalea;ul Haq, Muhammad Fahim;Qadir, Muhammad Imran 6485
Research over the years has progressively and sequentially provided near complete resolution of regulators of the DNA repair pathways which are so important for cancer prevention. Ataxia-telangiectasia mutated kinase (ATM), a high-molecular-weight PI3K-family kinase has emerged as a master regulator of DNA damage signaling and extensive cross-talk between ATM and downstream proteins forms an interlaced signaling network. There is rapidly growing scientific evidence emphasizing newly emerging paradigms in ATM biology. In this review, we provide latest information regarding how oxidative stress induced activation of ATM can be utilized as a therapeutic target in different cancer cell lines and in xenografted mice. Moreover, crosstalk between autophagy and ATM is also discussed with focus on how autophagy inhibition induces apoptosis in cancer cells.
Histopathological Outcomes of Women with Abnormal Cervical Cytology: a Review of Literature in Thailand
Kietpeerakool, Chumnan;Tangjitgamol, Siriwan;Srisomboon, Jatupol 6489
Cervical cytology remains the principal screening method to detect pre-invasive and invasive cervical lesions. Management of abnormal cervical cytology depends on the risk of encountering a significant cervical lesion or high-grade cervical disease. These risks may vary in different areas across the country. Thus, determining the rate of significant cervical lesion associated with each type of abnormal cervical cytology in each area is of critical importance for designing area-specific management approach. This review was conducted to evaluate the rate of high-grade cervical disease among Thai women with abnormal cervical cytology. A relatively high incidence of underlying significant lesions including invasive disease was demonstrated even in those having only minimal smear abnormality. This baseline information is crucial and must be taken into consideration in management of women with abnormal cytological screening to achieve the goals of comprehensive cervical cancer control in Thailand.
TRAIL Based Therapy: Overview of Mesenchymal Stem Cell Based Delivery and miRNA Controlled Expression of TRAIL
Attar, Rukset;Sajjad, Farhana;Qureshi, Muhammad Zahid;Tahir, Fizza;Hussain, Ejaz;Fayyaz, Sundas;Farooqi, Ammad Ahmad 6495
Rapidly increasing number of outstanding developments in the field of TRAIL mediated signaling have revolutionized our current information about inducing and maximizing TRAIL mediated apoptosis in resistant cancer cells. Data obtained with high-throughput technologies have provided finer resolution of tumor biology and now it is known that a complex structure containing malignant cells strictly coupled with a large variety of surrounding cells constitutes the tumor stroma. Utility of mesenchymal stem cells (MSCs) as cellular vehicles has added new layers of information. There is sufficient experimental evidence substantiating efficient gene deliveries into MSCs by retroviral, lentiviral and adenoviral vectors. Moreover, there is a paradigm shift in molecular oncology and recent high impact research has shown controlled expression of TRAIL in cancer cells on insertion of complementary sequences for frequently downregulated miRNAs. In this review we have attempted to provide an overview of utility of TRAIL engineered MSCs for effective killing of tumor and potential of using miRNA response elements as rheostat like switch to control expression of TRAIL in cancer cells.
Determinants of Health Information-Seeking Behavior: Implications for Post-Treatment Cancer Patients
Jung, Minsoo 6499
Health information-seeking behavior (HISB) is active need-fulfillment behavior whereby health information is obtained from diverse sources, such as the media, and has emerged as an important issue within the transforming medical environment and the rise of medical consumers. However, little is known about the factors that affect HISB and its associations, and the health outcome of HISB. The aim of this study was to examine individual and social contextual factors associated with HISB and to systematically review their effects on health status among post-treatment cancer patients. Individual determinants of HISB included demographic factors, psychosocial factors, perceived efficacy and norms, and health beliefs. Contextual determinants of HISB encompassed community characteristics, neighborhood social capital, and media advocacy. Improving through factors on these two levels, HISB raised individuals' self-care management skills and medical treatment compliance, and enhanced shared decision-making and medical treatment satisfaction. Moreover, because HISB can differ according to individuals' social contextual conditions, it can give rise to communication inequalities. Because these can ultimately lead to health disparities between groups, social interest in HISB and balanced HISB promotion strategies are necessary.
Association of a miR-502-Binding Site Single Nucleotide Polymorphism in the 3'-Untranslated Region of SET8 and the TP53 Codon 72 Polymorphism with Cervical Cancer in the Chinese Population
Yang, Shao-Di;Cai, Yan-Lin;Jiang, Pei;Li, Wen;Tang, Jian-Xin 6505
Objective: This study was conducted to identify whether polymorphic variants of set domain-containing protein 8 (SET8) and tumor protein p53 (TP53) codon 72, either independently or jointly, might be associated with increased risk for cervical cancer. Methods: We genotyped SET8 and TP53 codon 72 polymorphisms of peripheral blood DNA from 114 cervical cancer patients and 200 controls using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and direct DNA sequencing. Results: The frequency of SET8 CC (odds ratios (OR) = 2.717, 95% CI=1.436-5.141) or TP53 GG (OR=2.168, 95% CI=1.149-4.089) genotype was associated with an increased risk of cervical cancer on comparison with the SET8 TT or TP53 CC genotypes, respectively. In additional, interaction between the SET8 and TP53 polymorphisms increased the risk of cervical cancer in a synergistic manner, with the OR being 9.913 (95% CI=2.028-48.459) for subjects carrying both SET8 CC and TP53 GG genotypes. Conclusion: These data suggest that there are significant associations between the miR-502-binding site SNP in the 3'-UTR of SET8 and the TP53 codon 72 polymorphism with cervical cancer in Chinese, and there is a gene-gene interaction.
Significance of Thrombocytosis in Clinicopathologic Characteristics and Prognosis of Gastric Cancer
Li, Fang-Xuan;Wei, Li-Juan;Zhang, Huan;Li, Shi-Xia;Liu, Jun-Tian 6511
Purpose: We aimed to study the relationship between thrombocytosis and clinical features of gastric cancerfocussing on platelet counts and gastric cancer progression through different TNM stages. Methods: According to the normal range of platelet count in our institution, 1,596 patients were divided to two groups: a thrombocytosis group (120 patients, > $400{\times}1000/{\mu}L$) and a control group (1,476 patients, ${\leq}400{\times}1000/{\mu}L$). Results: The incidence of thrombocytosis was 7.5%. Higher platelet counts were observed in patients with older age, larger tumor size, deeper invasion, lymph node metastasis, distant metastasis and advanced TNM stage. In multivariate logistic regression, tumor size, depth of tumor invasion, lymph node metastasis and TNM stage were independent risk factors for thrombocytosis of gastric cancer patients. On prognostic analysis, age, tumor size, tumor location, histologic type, depth of tumor invasion, lymph node metastasis, distant metastasis and TNM stage and platelet count were important factors. Tumor size, invasion depth, lymph node metastasis, TNM stage and the platelet count were independent prognostic factors. Conclusion: Thrombocytosis is associated with clinical features of gastric cancer patients and correlates with a poor prognosis.
Comparison of Radical Cystectomy and Chemoradiotherapy in Patients with Locally Advanced Bladder Cancer
Ikeda, Masaomi;Matsumoto, Kazumasa;Nishi, Morihiro;Tabata, Ken-Ichi;Fujita, Tetsuo;Ishiyama, Hiromichi;Hayakawa, Kazushige;Iwamura, Masatsugu 6519
The aim of this study was to evaluate the clinical outcomes of radical cystectomy (RC) and concurrent chemoradiotherapy (CRT) with methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) in patients with locally advanced bladder cancer (BC). From December 2000 to February 2012, 72 patients with locally advanced BC (T3-4a, N0 or N+, M0) received either RC or CRT. RC with bilateral pelvic lymph node dissection including the common iliac region as the standard procedure. Patients in the CRT group received one cycle of MVAC followed by radiotherapy with a half dose of MVAC and then two more cycles of MVAC. Standard fractionation at a daily dose of 1.8-2.0 Gy was used, with a median total dose of 50 Gy (range, 45-60 Gy). The 3-year progression-free survival (PFS) rates in the RC and CRT groups were 56.2% and 25.6%, respectively (p=-0.015) and the 3-year overall survival (OS) rates were 63.5% and 48.1% (p=0.272). Multivariate Cox proportional hazards regression analysis with application of a propensity score indicated that RC was a significant predictor of PFS (p=0.033) but not of OS (p=0.291). Among patients with locally advanced BC, PFS was significantly prolonged in the RC group compared with the CRT group. However, RC was not a significant predictor of OS. Although the sample size in this study was small, the results suggest that patient background and postoperative quality of life should be considered when choosing treatment strategy for locally advanced BC.
Health Beliefs and Breast Self-Examination among Female University Nursing Students in Turkey
Erbil, Nulufer;Bolukbas, Nurgul 6525
Background: The aim of this study was to determine the health beliefs and knowledge about breast self examination (BSE) and the actual BSE habits of female university nursing students. Materials and Methods: The study sample recruited 189 nursing students who agreed to participate in the study. Descriptive statistics, the Mann-Whitney U test, one way ANOVA test, t test and Pearson correlation analysis were used to analyse the data. Results: 83.1% of nursing students had knowledge about breast cancer (BC) and BSE in the study. BSE was practiced by 70.4% of nursing students; 21.8% of them performed BSE regularly. A fear of developing BC was an incentive for 85% of nursing students to practice BSE. The confidence subscale scores in the third and fourth years of students' university education were higher, and the barrier subscale score in these same years was lower than their first years of study. Perception of benefit of nursing students experiencing breast-related discomfort exerted a positive effect. Nursing students with lower perception of barriesr performed BSE regularly. In conclusion, nursing students' years of university study, breast cancer knowledge, history of breast cancer in family, and BSE practice status were factors affecting their health beliefs. Conclusions: These study results indicate the importance of developing education and training programs which educate not only nursing students but all women about breast cancer, its symptoms, the importance of early diagnosis and of regular BSE.
Knowledge of Breast Cancer and Breast Self-Examination Practice among Iranian Women in Hamedan, Iran
Akhtari-Zavare, Mehrnoosh;Ghanbari-Baghestan, Abbas;Latiff, Latiffah A.;Matinnia, Nasrin;Hoseini, Mozhgan 6531
Background: In Iran, breast cancer is the most prevalent cancer in women and a major public health problem. Methods: A cross sectional study was carried out to determine knowledge on breast cancer and breast self-examination (BSE) practices of 384 females living in the city of Hamadan, Iran. A purposive sampling method was adopted and data were collected via face-to-face interviews based on a validated questionnaire developed for this study. Results: Among respondents 268 (69.8%) were married and 144 (37.5%) of the respondents reported having a family history of breast cancer. One hundred respondents (26.0%) claimed they practiced BSE. Level of breast cancer knowledge was significantly associated with BSE practice (p=0.000). There was no association with demographic details (p<0.05). Conclusion: The findings showed that Iranian women's knowledge regarding breast cancer and the practice of BSE is inadequate. Targeted education should be implemented to improve early detection of breast cancer.
Systemic Analysis on Risk Factors for Breast Cancer Related Lymphedema
Zhu, Ya-Qun;Xie, Yu-Huan;Liu, Feng-Huan;Guo, Qi;Shen, Pei-Pei;Tian, Ye 6535
Background: To evaluate risk factors for upper extremity lymphedema due to breast cancer surgery. Materials and Methods: Clinical studies published on PubMed, Ovid, EMbase, and Cochrane Library from January 1996 to December 2012 were selected. Results: Twenty-five studies were identified, including 12,104 patients. Six risk factors related to the incidence of lymphedema after breast cancer treatment were detected: axillary lymph node dissection (OR=3.73, 95%CI 1.16 to 11.96), postoperative complications (OR=2.64, 95%CI 1.10 to 6.30), hypertension (OR=1.83, 95%CI 1.38 to 2.42), high body mass index (OR=1.80, 95%CI 1.30 to 2.49), chemotherapy (OR=1.38, 95%CI 1.07 to 1.79) and radiotherapy (OR=1.35, 95%CI 1.10 to 1.66). We found significant protective factors for lymphedema: pathologic T classification (OR=0.57, 95%CI 0.36 to 0.91) and stage (OR=0.60, 95%CI 0.39 to 0.93), while some factors, like age, number of positive lymph nodes, number of lymph node dissection, demonstrated no obvious correlation. Conclusions: Axillary lymph node dissection, postoperative complications, hypertension, body mass index, chemotherapy, radiotherapy are risk factors for lymphedema after breast cancer treatment. Attention should be paid to patients with risk factors to prevent the occurrence of lymphedema.
miR-124 Inhibits Growth and Invasion of Gastric Cancer by Targeting ROCK1
Hu, Cong-Bing;Li, Qiao-Lin;Hu, Jian-Fei;Zhang, Qiang;Xie, Jian-Ping;Deng, Li 6543
MicroRNAs (miRNAs) act as critical regulators of genes involved in many biological processes. Aberrant alteration of miRNAs have been found in many cancers, including gastric cancer (GC), but the molecular mechanisms are not well understood. Herein, we investigated the role of miR-124 in GC. We found that its expression was significantly reduced in both GC tissue samples and cell lines. Forced expression of miR-124 suppressed GC cell proliferation, migration, and invasion. Furthermore, the Rho-associated protein kinase (ROCK1) was identified as a direct target of miR-124 in GC cells. Finally, silencing of ROCK1 showed similar effects as miR-124 overexpression, while supplementation of ROCK1 remarkably restored the cell growth and invasion inhibited by miR-124. Together, our data demonstrate that miR-124 acts as a tumor suppressor by targeting ROCK1, and posit miR-124 as a novel strategy for GC treatment.
Gender Differences in Marital Disruption among Patients with Cancer: Results from the Korean National Health and Nutrition Examination Survey (KNHANES)
Song, Hai-Yan;Kwon, Jeoung-A;Choi, Jae-Woo;Kim, Sun-Jung;Park, Eun-Cheol 6547
Background: Cancer is a major life event that imposes huge economic and mental burdens on patients and families. In addition, the diagnosis of cancer also causes significant family discordance that can lead to marital problems such as divorce or separation. The aim of this study was to investigate the association and any related gender differences between cancer diagnosis and marital disruption among cancer survivors. Materials and Methods: We used the recent cross-sectional Korea National Health and Nutrition Examination Survey ($4^{th}$ and $5^{th}$; Years 2008-2012). The study participants were 623 married cancer survivors over the age of 19. A multivariate logistic regression analysis was conducted to estimate odds ratios. Results: After adjusting for socioeconomic status and health-related behaviors, the odds ratio of marital disruption among female cancer survivors compared with male cancer survivors was 3.94 (95%CI 1.30-11.94; p=0.02). The odds ratio of marital disruption for the below-average economic level compared with the above-average economic level was 5.64 (95%CI: 1.03-31.02; p=0.05). When compared with the non-smoking cancer survivors, the smoking cancer survivors had an OR of marital disruption equal to 2.94 (95%CI: 1.08-8.00; p=0.03). Conclusions: The findings of this study suggest that the odds of marital disruption among female cancer survivors are higher than those among their male couterparts. Medical practitioners should be sensitive to early signs of marital discord in couples affected by a cancer diagnosis. Early identification and psychosocial intervention might reduce the frequency of divorce and separation and thus improve quality of life and quality of care for cancer survivors.
Analysis of Motivating Factors for Smokeless Tobacco Use in Two Indian States
Danawala, Saba Ashraf;Arora, Monika;Stigler, Melissa Harrell 6553
Background: This study was conducted to gauge how the demographic profile of smokeless tobacco (SLT) users from Gujarat and Andhra Pradesh, India, differs from that of smokers. It also addresses how factors associated with the initiation and continuation of smokeless tobacco vary by age, gender, and education. Materials and Methods: We analyzed 2011 cross-sectional survey data collected from 4,759 respondents (smokers/SLT users/non-users) in both states. Chi-square analysis was used to make comparisons between the demographic profiles of smokers and SLT users. Multivariable logistic regression analysis was used to obtain the odds ratios (ORs) for initiation and continuation factors regressed on socio-demographic variables (age, gender, education). Results: Initiation-women were less likely than men to report "peer pressure", "fashion statement", and "stress/coping" as relevant factors for SLT use (OR: 0.45 CI: 0.30-0.70; OR: 0.42 CI: 0.24-0.74; OR: 2.47, CI: 1.47-4.15). Older age groups had lower odds of choosing "peer pressure" than the 15-24 year olds. Respondents with 11 or more years of education were more likely to report "stress/coping" than those with no education (OR: 2.82, CI: 1.06-7.48). Continuation-women were less likely than men to choose "relaxation", and "distance from family" as important continuation factors (OR: 0.50, CI:0.32-0.80; OR: 0.20, CI: 0.06-0.65). All age groups were less likely to choose "stimulation" as a factor than the youngest group. Conclusions: Along with confirming and expanding upon previous literature, the findings of this study should encourage further SLT research in women and younger age groups (15-24 and 24-44). They also confirm the need for SLT prevention and cessation interventions in India in other community-based settings, besides schools.
Efficacy and Safety of Bevacizumab in Chinese Patients with Metastatic Colorectal Cancer
Zhu, Li-Ming;Zhao, Ya-Zhen;Ju, Hai-Xing;Liu, Lu-Ying;Chen, Lei;Liu, Bi-Xia;Xu, Qi;Luo, Cong;Ying, Jie-Er;Yang, Yun-Shan;Zhong, Hai-Jun 6559
Objective: To evaluate the efficacy and safety of bevacizumab in the treatment of patients with metastatic colorectal cancer (mCRC). Methods: In a single-center, observational study of 91 Chinese patients with mCRC who received bevacizumab in combination with chemotherapy was conducted. Objective response rates (ORRs), progression-free survival (PFS), overall survival (OS) and adverse events were recorded, and the relationships between various clinical factors and PFS or OS were evaluated by Cox proportional hazards models. Results: Treatment with bevacizumab and chemotherapy was effective and tolerable. Univariate analysis showed that PFS and OS were significantly associated with the Eastern Cooperative Oncology Group performance status (ECOG-PS) score, duration of bevacizumab exposure, and whether chemotherapy was continued after discontinuation of bevacizumab treatment. A multivariate analysis showed that the duration of bevacizumab exposure and whether chemotherapy was continued after discontinuation of bevacizumab were independent prognostic factors for PFS and OS. Conclusion: In Chinese mCRC population, the shorter the duration of exposure to bevacizumab and chemotherapy, the worse the prognosis is.
Clinical Observation and Therapeutic Evaluation of Rh-endostatin Combined with DP Regimen in Treating Patients with Advanced Esophageal Cancer
Deng, Wen-Ying;Song, Tao;Li, Ning;Luo, Su-Xia;Li, Xiang 6565
Objective: To observe the curative effects of rh-endostatin combined with DP regimen in treating patients with advanced esophageal cancer and analyze the correlation of CT perfusion (CTP) parameters and the expression of vascular endothelial growth factor (VEGF). Methods: Twenty patients with esophageal cancer confirmed pathologically were randomly divided into combined treatment (rh-endostatin+DP regimen) group and single chemotherapy group, 10 patients in each group, respectively. All patients were given conventional CT examination and CTP imaging for primary tumor. The level of VEGF, the size of tumor and CTP parameters (BF, BV, PS and MTT) before treatment and after 2 cycles of treatment were determined for the comparison and the correlation between CTP parameters and VEGF expression was analyzed. Results: the therapeutic effect of rh-endostatin+DP regimen group was superior to single chemotherapy group. VEGF level after treatment in rh-endostatin+DP regimen group was obviously lower than single chemotherapy group (P<0.01). The expression of VEGF had positive correlation with BF and BV but negative correlation with MTT. Compared with treatment before for rh-endostatin+DP regimen group, BF, BV and PS decreased while MTT increased after treatment (P<0.05). However, there were no significant differences between treatment before and after treatment in single chemotherapy (P>0.05). Conclusions: Rh-endostatin can down-regulate the expression of VEGF in esophageal cancer, change the state of hypertransfusion and high permeability of tumor vessels and had the better curative effect and slighter adverse reactions when combined with chemotherapy.
Reliability and Validity of the Alcohol Use Disorders Identification Test - Consumption in Screening for Adults with Alcohol Use Disorders and Risky Drinking In Japan
Osaki, Yoneatsu;Ino, Aro;Matsushita, Sachio;Higuchi, Susumu;Kondo, Yoko;Kinjo, Aya 6571
Background: Alcohol is well established as a risk factor for cancer development in many organ sites. To assess the reliability and validity of the Alcohol Use Disorders Identification Test - Consumption (AUDIT-C) for detecting alcohol use disorders or risky drinking in Japanese adults the present study was conducted. Materials and Methods: A test-retest method was applied with a 2-week interval with 113 health care employees. The k coefficient, Cronbach's coefficient alpha, Spearman's correlation coefficient, and intraclass correlation coefficient (ICC) were determined and the validity of the AUDIT-C was analyzed using the data from a nationwide survey on adult alcohol use conducted in 2008 (n=4,123). Results: The reliability of the AUDIT-C score was high (${\kappa}$ coefficient=0.63, Cronbach's alpha=0.98, correlation coefficient=0.95, and ICC=0.95). According to the likelihood ratio and Youden index, appropriate cutoffs for the AUDIT-C were ${\geq}5points$ in men and ${\geq}4$ points in women. The sensitivity and specificity of these cutoffs for identifying ${\geq}8$ points on the AUDIT were 0.88 and 0.80, respectively, for men (positive likelihood ratio [LR+]=4.5) and 0.96 and 0.87, respectively, for women (LR+=7.7). The sensitivity and specificity of the cutoffs for identifying ${\geq}12$ points on the AUDIT were 0.90 and 0.84, respectively, for men (LR+=5.8) and 0.93 and 0.94, respectively, for women (LR+=15.8). The sensitivity and specificity of the cutoffs for identifying ${\geq}16$ points on the AUDIT were 0.93 and 0.80, respectively, for men (LR+=4.7) and 0.92 and 0.98, respectively, for women (LR+=55.6). With higher scores on the AUDIT, the specificity decreased and false-positives increased. The appropriate cutoffs for identifying risky drinking were the same for both genders. Conclusions: The reliability and validity of the AUDIT-C are high, indicating that it is useful for identifying alcohol use disorders or risky drinking among the general population in Japan, a group at high risk of cancer development.
Chemopreventive Activity of Turmeric Essential Oil and Possible Mechanisms of Action
Liju, Vijayasteltar Belsamma;Jeena, Kottarapat;Kuttan, Ramadasan 6575
This study aimed to evaluate the antimutagenic and anticarcinogenic activity of turmeric essential oil as well as to establish biochemical mechanisms of action. Antimutagenicity testing was accomplished using strains and known mutagens with and without microsomal activation. Anticarcinogenic activity was assessed by topical application of 7, 12 - dimethylbenz[a]anthracene (DMBA) as initiator and 1% croton oil as promoter for the induction of skin papillomas in mice. Inhibition of p450 enzymes by TEO was studied using various resorufins and aminopyrene as substrate. Turmeric essential oil (TEO) showed significant antimutagenic activity (p<0.001) against direct acting mutagens such as sodium azide ($NaN_3$), 4-nitro-O-phenylenediamine (NPD) and N-methyl-N-nitro N'nitrosoguanine (MNNG). TEO was found to have significant antimutagenic effect (>90%) against mutagen needing metabolic activation such as 2-acetamidoflourene (2-AAF). The study also revealed that TEO significantly inhibited (p<0.001) the mutagenicity induced by tobacco extract to Salmonella TA 102 strain. DMBA and croton oil induced papilloma development in mice was found to be delayed and prevented significantly by TEO application. Moreover TEO significantly (P<0.001) inhibited isoforms of cytochrome p450 (CYP1A1, CYP1A2, CYP2B1/2, CYP2A, CYP2B and CYP3A) enzymes in vitro, which are involved in the activation of carcinogens. Results indicated that TEO is antimutagenic and anticarcinogenic and inhibition of enzymes (p450) involved in the activation of carcinogen is one of its mechanisms of action.
Trichostatin A-induced Apoptosis is Mediated by Krüppel-like Factor 4 in Ovarian and Lung Cancer
Zohre, Sadeghi;Kazem, Nejati-Koshki;Abolfazl, Akbarzadeh;Mohammad, Rahmati-Yamchi;Aliakbar, Movassaghpour;Effat, Alizadeh;Zahra, Davoudi;Hassan, Dariushnejad;Nosratollah, Zarghami 6581
Background: The istone deacetylase (HDAC) inhibitor trichostatin A (TSA) is known to mediate the regulation of gene expression and antiproliferation activity in cancer cells. Kr$\ddot{u}$ppel-like factor 4 (klf4) is a zinc finger-containing transcription factor of the SP/KLF family, that is expressed in a variety of tissues and regulates cell proliferation, differentiation, tumorigenesis, and apoptosis. It may either either function as a tumor suppressor or an oncogene depending on genetic context of tumors. Aims: In this study, we tested the possibility that TSA may increase klf4 expression and cancer cell growth inhibition and apoptosis in SKOV-3 and A549 cells. Materials and Methods: The cytotoxicity of TSA was determined using the MTT assay test, while klf4 gene expression was assessed by real time PCR andto ability of TSA to induce apoptosis using a Vybrant Apoptosis Assay kit. Results: Our results showed that TSA exerted dose and time dependent cytotoxicity effect on SKOV-3 and A549 cells. Moreover TSA up-regulated klf4 expression. Flow cytometric analysis demonstrated that apoptosis was increased after TSA treatment. Conclusions: Taken together, this study showed that TSA increased klf4 expression in SKOV3 and A549 cell lines, consequently, klf4 may played a tumor-suppressor role by increasing both cell growth inhibition and apoptosis. This study sheds light on the details of molecular mechanisms of HDACI-induced cell cycle arrest and apoptosis.
Further Study on Pemetrexed based chemotherapy in Treating Patients with Advanced Gastric Cancer (AGC)
Liu, Jin;Huang, Xin-En;Feng, Ji-Feng 6587
Objective: To further observe the efficacy and safety of pemetrexed, combined with Irinotecan or oxaliplatin or cisplatin in treating patients with advanced gastric cancer as second-line or third-line chemotherapy. Methods: From September 2013 to February 2014 we recruited 50 patients with advanced gastric cancer, with stage IV disease or postoperative recurrence, or unresectable. Then treated with pemetrexed based chemotherapy. After two cycles of treatment, efficacy and toxicity were evaluated. Results: Pemetrexed based chemotherapy was used as second-line in 33 patients, RR(CR+PR) is 41.2%. And achieved 36.4% when used as third-line. Overall response rate of 50 patients treated with Pemetrexed based treatment was 38% (CR+PR). Treatment related side effects were bone marrow suppression, vomiting, hepatic dysfunction and malaise.No treatment related death occurred. Conclusions: Treatment with pemetrexed based chemotherapy is active and is well tolerated in patients with advanced gastric cancer.
Role of P14 and MGMT Gene Methylation in Hepatocellular Carcinomas: a Meta-analysis
Li, Cheng-Cheng;Yu, Zhuang;Cui, Lian-Hua;Piao, Jin-Mei;Liu, Meng 6591
Background: This meta-analysis was performed to investigate the relationship between methylation of the P14 and O6-methylguanine-DNA methyltransferase (MGMT) genes and the risk of hepatocellular carcinoma (HCC). Materials and Methods: We searched PubMed, EMBASE, the Chinese Biomedical Database (CBM), and the China National Knowledge Infrastructure (CNKI) databases to identify relevant studies that analysed HCC tissues for P14 and MGMT gene methylation status; we then performed a meta-analysis. Odds ratios (ORs) and 95% confidence intervals (95%CIs) were calculated to evaluate the association between gene methylation and the risk of HCC. Results: Ten studies that assessed P14 gene methylation in 630 HCC tumour tissues and nine studies analysing MGMT methylation in 497 HCC tumour tissues met our inclusion criteria. Our meta-analysis revealed that the rate of P14 methylation was significantly higher in HCCs than in adjacent tissues (OR 3.69, 95%CI 1.63-8.35, p=0.002), but there was no significant difference in MGMT methylation between HCC and adjacent tissues (OR 1.76, 95%CI 0.55-5.64, p=0.34). A subgroup analysis according to ethnicity revealed that P14 methylation was closely related to the risk of HCC in Chinese and Western individuals (Chinese, OR 7.74, 95%CI 1.36-44.04, p=0.021; Western, OR 3.60, 95%CI 1.49-8.69, p=0.004). Furthermore, MGMT methylation was not correlated with the risk of HCC in Chinese individuals (OR 2.42, 95%CI 0.76-7.73, p=0.134). The combined rate of P14 methylation was 35% (95%CI 24-48%) in HCC tumour tissues and 11% (95%CI 4-27%) in adjacent tissues, whereas the combined rate of MGMT methylation was 15% (95%CI 6-32%) in HCC and 10% (95%CI 4-22%) in adjacent tissues. Conclusions: These results suggest that the risk of HCC is related to P14 methylation, but not MGMT methylation. Therefore, P14 gene methylation may be a potential biomarker for the diagnosis of HCC.
Five Year Survival of Women with Breast Cancer in Yazd
Fallahzadeh, Hossein;Momayyezi, Mahdieh;Akhundzardeini, Razie;Zarezardeini, Sadegh 6597
Background: Cancer is a non-communicable disease that is considered deadly in many cases. In recent years, the mortality rates from breast cancer have increased with increasing incidences. The present study was conducted to determine five year survival of women with breast cancer in Yazd, in the central region of Iran. Materials and Methods: In a prospective study, data were obtained from the patient's medical records with breast cancer that were referred to the Shahid Sadoughi hospital and radiotherapy center from 2002-2007 and followed up for 5 years. The data collected were analyzed by SPSS/16 and Kaplan-Meyer test and log-rank test and Cox proportional hazard model was used. Results: The mean age of breast cancer diagnosis was $48.3{\pm}11.7$ years. The 1-, 2-, 3-, 4- and 5-year cumulative survivals for breast cancer patients were 95%, 86%, 82%, 76% and 70%, respectively. There were significant differences with age distribution (p=0.006). A significant decrease in the 5-year survival in patients with involvement of lymph nodes was lso observed. Conclusions: Education for early diagnosis in women must be considered and these findings support the need for breast cancer screening programs.
Evaluation of an Educational Program on Cervical Cancer for Rural Women in Mangalore, Southern India
Mary, Bright;D'Sa, Juliana Linnette 6603
Cervical cancer is one of the leading causes of cancer in women worldwide. One way by which the incidence of this malignant disease can be minimized is by imparting knowledge through health education. This study aimed at developing an educational package on cervical cancer (EPCC) and determining its effectiveness in terms of significant increase in knowledge of rural women regarding cervical cancer. A one group pre-test, post-test design was adopted. Thirty rural women were selected using a convenient sampling method. Data were collected using a demographic questionnaire and a structured knowledge questionnaire developed by the researchers. The EPCC was designed for a duration of one hour and 10 minutes. The structured knowledge questionnaire was first administered as the pre-test, following which knowledge on cervical cancer was imparted using the EPCC. On the 8th day, the post-test was administered. Data were analyzed using descriptive and inferential statistics. The mean post-test knowledge score of the women regarding cervical cancer was significantly higher than that of their mean pre-test score, indicating that the EPCC was effective in improving the knowledge of rural women on cervical cancer. The association between pre-test knowledge scores and selected demo-graphic variables were computed using chi-square test showed that pre-test knowledge score of the women regarding cervical cancer was independent of all the socio-demographic variables. It was concluded that the EPCC is effective in improving the knowledge of women, regarding cervical cancer. Since the prevalence of cervical cancer is high, there is an immediate need to educate women on prevention of cervical cancer.
Prevalence and Risk Factors for Opisthorchis viverrini Infections in Upper Northeast Thailand
Thaewnongiew, Kesorn;Singthong, Seri;Kutchamart, Saowalux;Tangsawad, Sasithorn;Promthet, Supannee;Sailugkum, Supan;Wongba, Narong 6609
Opisthorchis viverrini is an ongoing public health problem in Northeast Thailand. Despite continuous efforts for decades by healthcare organizations to overcome this problem, infection rates remain high. To enable related personnel to identify and address the various issues effectively, a cross-sectional study was performed to investigate prevalence and risk factors for opisthorchiasis. The target group was 3,916 Thai residents of Northeast Thailand who were 15 or over. Participants were recruited using the 30 clusters sampling technique. The data were gathered through questionnaires, focus group discussions, in-depth interviews, and stool examinations for parasite eggs (using the Modified Kato Katz method). The data were analyzed using descriptive and inference statistics; in order to ascertain the risk factors and test them using the odds ratio and multiple logistic regressions. The prevalence of opisthorchiasis was 22.7% (95%CI: 0.26 to 0.24). The province with the highest prevalence was Nakhorn Phanom (40.9%; female to male ratio =1:1.2). The age group with the highest prevalence was 40-49 year olds. All age groups had a prevalence >20%. Four of seven provinces had a prevalence >20%. The factors related to opisthorchiasis were (a) sex, (b) age (especially > 50), (c) proximity and duration living near a water body, and (d) eating raw and/or fermented fish. In order to reduce the prevalence of opisthorchiasis, the focus in populations living in upper Northeast Thailand should be changing their eating behaviors as appropriate to their tradition and context.
Association between the XRCC3 Thr241Met Polymorphism and Breast Cancer Risk: an Updated Meta-analysis of 36 Case-control Studies
Mao, Chang-Fei;Qian, Wen-Yi;Wu, Jian-Zhong;Sun, Da-Wei;Tang, Jin-Hai 6613
Background: The X-ray repair cross-complementing group 3 (XRCC3) is a highly suspected candidate gene for cancer susceptibility. Attention has been drawn upon associations of the XRCC3 Thr241Met polymorphism with breast cancer risk. However, the previous published findings remain controversial. Hence, we performed a meta-analysis to accurately evaluate any association between breast cancer and XRCC3 T241M (23, 812 cases and 25, 349 controls) in different inheritance models. Materials and Methods: PubMed and Web of Science databases were searched systematically until December 31, 2013 to obtain all the records evaluating the association between the XRCC3 Thr241Met polymorphism and breast cancer risk. Crude odds ratios (ORs) together with 95% confidence intervals (CIs) were used to assess the strength of associations. Results: When all eligible studies were pooled into the meta analysis of XRCC3 T241M polymorphism, a significantly increased breast cancer risk was observed in heterozygote comparison (OR=1.06, 95%CI=1.01-1.12). No significant associations were found in other models. In subgroup analysis, this polymorphism seemed to be associated with elevated breast risk in Asians. No publication bias was detected. Conclusions: This meta-analysis suggests that the T241M polymorphism confers a weakly increased breast cancer risk. A study with the larger sample size is needed to further evaluate gene-gene and gene-environment interactions of the XRCC3 T241M polymorphism with breast cancer risk.
XPD Lys751Gln and Asp312Asn Polymorphisms and Susceptibility to Skin Cancer: A Meta-Analysis of 17 Case-control Studies
Zhu, Hai-Li;Bao, Ji-Ming;Lin, Pei-Xin;Li, Wen-Xia;Zou, Zhen-Ning;Huang, Ye-En;Chen, Qing;Shen, Hong 6619
Background: Numerous studies have explored the influence of XPD Lys751Gln and/or Asp312Asn polymorphisms on skin cancer susceptibility. However, the results remain inconclusive. To derive a more precise estimation, we conducted a comprehensive search to identify all available published studies and performed a meta-analysis. Materials and Methods: Electronic literature searches of the PubMed, CBM and CNKI databases were performed up to March 2014. Odds ratios (ORs) with 95% confidence intervals (CIs) were applied to assess the strength of associations. Results: Seventeen case-control studies were included with a total sample size of 6, 113 cases and 11, 074 controls for the XPD Lys751Gln polymorphism, and 10 studies (3, 840cases and 7, 637 controls) for the XPD Asp312Asn polymorphism were pooled for analysis. Overall, no significant associations were found between the XPD Lys751Gln polymorphism and skin cancer risk in any genetic model. On stratified analysis by tumor type, XPD Lys751Gln polymorphism was not associated with increased risk of non-melanoma skin cancer, but was significantly related with increased risk of cutaneous melanoma (Gln/Gln vs Lys/Lys: OR=1.15, 95%CI=1.02-1.29, p=0.023; dominant model: OR=1.09, 95%CI=1.01-1.18, p=0.036). For the XPD Asp312Asn polymorphism, no significant association with skin cancer risk was observed in overall or subgroup analyses. Conclusions: The present meta-analysis suggests that the XPD Lys751Gln polymorphism may contribute to the risk of cutaneous melanoma from currently available evidence. Further investigations are needed to obtain more insight into possible roles of these two polymorphisms in skin carcinogenesis.
Fungal Taxol Extracted from Cladosporium oxysporum Induces Apoptosis in T47D Human Breast Cancer Cell Line
Raj, Kathamuthu Gokul;Sambantham, Shanmugam;Manikanadan, Ramar;Arulvasu, Chinnansamy;Pandi, Mohan 6627
Purpose: The present study concerns molecular mechanisms involved in induction of apoptosis by a fungal taxol extracted from the fungus Cladosporium oxysporum in T47D human breast cancer cells. Materials and Methods: Apoptosis-induced by the fungal taxol was assessed by MTT assay, nuclear staining, DNA fragmentation, flow cytometry and pro- as well as anti-apoptotic protein expression by Western blotting. Results: Our results showed inhibition of T47D cell proliferation with an $IC_{50}$ value of $2.5{\mu}M/ml$ after 24 h incubation. It was suggested that the extract may exert its anti-proliferative effect on human breast cancer cell line by suppressing growth, arresting through the cell cycle, increase in DNA fragmentation as well as down-regulation of the expression of NF-${\kappa}B$, Bcl-2 and Bcl-XL and up-regulation of pro-apoptotic proteins like Bax, cyt-C and caspase-3. Conclusions: We propose that the fungal taxol contributes to growth inhibition in the human breast cancer cell through apoptosis induction via a mitochondrial mediated pathway, with possible potential as an anticancer therapeutic agent.
Cytotoxicity Assessments of Portulaca oleracea and Petroselinum sativum Seed Extracts on Human Hepatocellular Carcinoma Cells (HepG2)
Farshori, Nida Nayyar;Al-Sheddi, Ebtesam Saad;Al-Oqail, Mai Mohammad;Musarrat, Javed;Al-Khedhairy, Abdulaziz Ali;Siddiqui, Maqsood Ahmed 6633
The Pharmacological potential, such as antioxidant, anti-inflammatory, and antibacterial activities of Portulaca oleracea (PO) and Petroselinum sativum (PS) extracts are well known. However, the preventive properties against hepatocellular carcinoma cells have not been explored so far. Therefore, the present investigation was designed to study the anticancer activity of seed extracts of PO and PS on the human hepatocellular carcinoma cells (HepG2). The HepG2 cells were exposed with $5-500{\mu}g/ml$ of PO and PS for 24 h. After the exposure, cell viability by 3-(4,5-dimethylthiazol-2yl)-2,5-biphenyl tetrazolium bromide (MTT) assay, neutral red uptake (NRU) assay, and cellular morphology by phase contrast inverted microscope were studied. The results showed that PO and PS extracts significantly reduced the cell viability of HepG2 in a concentration dependent manner. The cell viability was recorded to be 67%, 31%, 21%, and 17% at 50, 100, 250, and $500{\mu}g/ml$ of PO, respectively by MTT assay and 91%, 62%, 27%, and 18% at 50, 100, 250, and $500{\mu}g/ml$ of PO, respectively by NRU assay. PS exposed HepG2 cells with $100{\mu}g/ml$ and higher concentrations were also found to be cytotoxic. The decrease in the cell viability at 100, 250, and $500{\mu}g/ml$ of PS was recorded as 70%, 33%, and 15% by MTT assay and 63%, 29%, and 17%, respectively by NRU assay. Results also showed that PO and PS exposed cells reduced the normal morphology and adhesion capacity of HepG2 cells. HepG2 cells exposed with $50{\mu}g/ml$ and higher concentrations of PO and PS lost their typical morphology, become smaller in size, and appeared in rounded bodies. Our results demonstrated preliminary screening of anticancer activity of Portulaca oleracea and Petroselinum sativum extracts against HepG2 cells, which can be further used for the development of a potential therapeutic anticancer agent.
Clinical Significance of Atypical Squamous Cells of Undetermined Significance in Detecting Preinvasive Cervical Lesions in Post-Menopausal Turkish Women
Tokmak, Aytekin;Guzel, Ali Irfan;Ozgu, Emre;Oz, Murat;Akbay, Serap;Erkaya, Salim;Gungor, Tayfun 6639
Background: To evaluate the clinical significance of atypical squamous cells of undetermined significance (ASCUS) in PAP test in post-menopausal women and compare with reproductive age women. Materials and Methods: A total of 367 patients who referred to our gynecologic oncology clinic were included to the study between September 2012 and August 2013. Data for 164 post-menopausal (group 1) and 203 pre-menopausal (group 2) women with ASCUS cytology were evaluated retrospectively. Immediate colposcopy and endocervical curettage was performed for both groups and conization for all women with a result suggestive of CIN2-3. Histopathological results and demographic features of patients were compared between the two groups. Results: Mean age of the patients was $54.6{\pm}6.5$ years in group 1 and $38{\pm}6.6$ years in group 2. Some 14 (8.5%) of post-menopausal women and 36 (17.7%) of pre-menopausal women were current smokers (p=011). Totals of 38 (23.2%) post-menopausal and 64 (31.5%) pre-menopausal women were assessed for HPV-DNA. High risk HPV was detected in 7 (4.3%) and 21 (10.3%), respectively (p=0.029). Final histopathological results recorded were normal cervix, low grade cervical intra-epithelial neoplasia (CIN 1), and high grade cervical intra-epithelial neoplasia (CIN2-3). In group 1 results were 84.8%, 12.2% and 1.8%, respectively, and in group 2 were 71.9%, 23.2% and 4.9%. There were no cases of micro invasive or invasive cervical carcinoma in either group. Two cases were detected as endometrial carcinoma in the menopausal group (1.2%). Conclusions: In current study we found that preinvasive lesions were statistically significantly higher in pre-menopausal women than post-menopausal women with ASCUS. Cervicitis was more common in menopausal women. Therefore, we think that in case of ASCUS in a post-menopausal woman there is no need for radical management.
Relationship between Breast Cancer and Levels of Serum Thyroid Hormones and Antibodies: a Meta-analysis
Shi, Xin-Zhu;Jin, Xing;Xu, Peng;Shen, Hong-Mei 6643
The breast and the thyroid are hormone responsive organs that are closely related with changes of endocrine function and glandular disease. An association between thyroid disorders and breast cancer (BC) risk has been suggested, although the results are inconclusive. The purpose of the present study was to summarize evidence supporting a relationship between BC and the level of thyroid hormones and antibodies. The MEDLINE and EMBASE electronic databases were searched for studies published between 2000 and 2014. The pooled effects were presented as weighted mean differences (WMD) with 95% confidence intervals (CI) using fixed or random effect models. We summarized the results of 8 cross-sectional studies with 4, 189 participants. The overall pooled results showed that the levels of $FT_3$ and $FT_4$ were significantly increased in patients with BC (WMD=1.592 pmol/l; 95% CI: 0.15-3.033 and WMD=0.461 ng/dl; 95% CI: 0.015-0.906; p=0.043). The TPOAb level in patients with BC was higher than that in the control group (WMD=81.4 IU/ml; 95% CI: 78.7-84.0; p=0.000). The overall pooled results of the TgAb with random effects analyses showed that the TgAb level was significantly increased in patients with BC (WMD=101.3 IU/ml; 95% CI: 48.7-153.9; p=0.000). The present results indicated that the serum levels of $FT_3$, TPOAb and TgAb are significantly higher in patients with breast cancer than in healthy controls.
Fenofibrate Increases Radiosensitivity in Head and Neck Squamous Cell Carcinoma via Inducing G2/M Arrest and Apoptosis
Liu, Jia;Ge, Yang-Yang;Zhu, Hong-Cheng;Yang, Xi;Cai, Jing;Zhang, Chi;Lu, Jing;Zhan, Liang-Liang;Qin, Qin;Yang, Yan;Yang, Yue-Hua;Zhang, Hao;Chen, Xiao-Chen;Liu, Zhe-Ming;Ma, Jian-Xin;Cheng, Hong-Yan;Sun, Xin-Chen 6649
Radiation therapy is an important treatment for head and neck squamous cell carcinoma (HNSCC). However, how to promote radiation sensitivity in HNSCC remains a challenge. This study aimed to investigate the radiosensitizing effects of fenofibrate on HNSCC and explore the underlying mechanisms. HNSCC cell lines CNE-2 and KB were subjected to ionizing radiation (IR), in the presence or absence of fenofibrate treatment. Cell growth and survival, apoptosis and cell cycle were evaluated. In addition, CNE-2 cells were xenografted into nude mice and subjected to IR and/or fenofibrate treatment. The expression of cyclinB and CDK1 was detected by Western blotting. Our results showed that fenofibrate efficiently radiosensitized HNSCC cells and xenografts in mice, and induced apoptosis and G2/M arrest via reducing the activity of the CDK1/cyclinB1 kinase complex. These data suggest that fenofibrate could be a promising radiosensitizer for HNSCC radiotherapy.
Determination of Sexual Problems of Turkish Patients Receiving Gynecologic Cancer Treatment: a Cross-sectional Study
Demirtas, Basak;Pinar, Gul 6657
Background: The present study aimed to determine the prevalence and types of sexual problems of Turkish patients receiving gynecologic cancer treatment. Materials and Methods: A cross-sectional convenience sample of 168 women completed the Index of Female Sexual Function (IFSF) and a Patient Identification Form in a hospital in Ankara, Turkey. Mean IFSF scores of the patients were low ($15.7{\pm}5.72$, out of a possible 45), indicating high rates of sexual problems. Results: Women frequently reported problems with dyspareunia (97.1%), vaginal dryness (97.6%), decreased sexual desire (91.1%), and difficulties of sexual arousal (92.9%) related with the cancer treatment process. They reported increased sexual problems following the period of treatment as compared to before treatment (p<0.05). Sexual dysfunction was associated with low educational and income levels, advanced age, TAH-BSO-LND surgery (total abdominal hysterectomy-bilateral salphingoopherectomylymph node dissection), experiencing side effects of chemotherapy, receiving chemotherapy in addition to surgery and radiotherapy (CT+RT+Surgery), and having a large number of chemotherapy cycles (p<0.05). Conclusions: Patients hoped for and expected counseling from healthcare professionals about their sexual functioning in relation to cancer treatments. Nurses and physicians can help to improve the overall quality of life for gynecologic cancer patients through sexual counseling.
Clinicopathologic Features and Molecular Subtypes of Breast Cancer in Young Women (Age ≤35)
Goksu, Sema Sezgin;Tastekin, Didem;Arslan, Deniz;Gunduz, Seyda;Tatli, Ali Murat;Unal, Dilek;Salim, Derya;Guler, Tunc;Coskun, Hasan Senol 6665
Introduction: Breast cancer in young women is a relatively rare disease; however it tends to be more aggressive and is the leading cause of cancer death in this population. The aim of this study is to investigate the clinical and biological features of breast cancer arising in young Turkish breast cancer patients. Materials and Methods: Patients with breast cancer aged 35 or less (${\leq}35$ years) were selected for the study. In total 211 cases were included. Pathologic features; histologic subtypes, grade, lymphovascular invasion, axillary involvement, and stage were recorded for each. Results: The most common subtype was luminal B (36.5%), followed by luminal A (30.8%), triple negative (23.2%) and HER2+(9.5%) subtypes. Twelve percent of the patients had stage 4, 32.7% had stage 3, 46.4% had stage 2, and 6.2% had stage 1 disease at the time of diagnosis. Mean tumour diameter was 3.87 cm (range 0.3-13 cm). The axillary lymph nodes were positive in 74.4% of the patients, while lympho-vascular invasion was seen in 56.4%. Some 9.5% of patients had grade 1, 51.2% had grade 2, and 31.8% had grade 3 tumors. Conclusions: Young women with breast cancer in Turkey are more likely to present with luminal B subtype. Tumors in young women are more likely to present with advanced disease, to be high grade and and to have more lymphovascular invasion. Further research should focus on whether we need new treatment strategies for young patients with breast carcinoma.
Are Primary Health Care Workers Aware of Cervical Cancer Risk?
Can, Huseyin;Erdem, Ozgur;Oztekin, Coskun;Celik, Sercan Bulut;Onde, Mete;Celepkolu, Tahsin;Ongel, Kurtulus 6669
Background: We here examined the awareness of female health employees (doctors, nurses, midwives) working in primary health care service about cervical cancer and its risk factors. Additionally attitude and behavior for gynecologic examination and pap smear screening wwere researched. Materials and Methods: This cross-sectional, descriptive study con cerned female health employees working at primary health care services in two southern cities of Turkey, over a four month period in 2013. Participants were recently or previously sexually active research was explained and verbal informed consent was obtained face to face. The questionnaire consisted of two parts; socio-demographic characteristics and level of knowledge about cervical cancer and its risk factors. Results: The average age of the participants (midwives 43.7%, n=143; nurses 40.4%, n=132; doctors 6.4%, n=21; emergency medical technicians and others, 9.5%, n=31; total, n=327) was $30.9{\pm}6.41$ years. 64.2% (n=210) were working in Diyarbakir and 35.8% (n=117) in Batman. A large proportion reported low knowledge and inadequate screening practice Conclusions: Health employees should be better informed about the importance of screening for cancers, given their preventive roles for the general population.
Elevated PIVKA-II is Associated with Early Recurrence and Poor Prognosis in BCLC 0-A Hepatocellular Carcinomas
Wang, Bei-Li;Tan, Qi-Wen;Gao, Xing-Hui;Wu, Jiong;Guo, Wei 6673
Background: To investigate the prognostic value of serum PIVKA-II (prothrombin induced by the absence of vitamin K or antagonist-II) in BCLC (Barcelona Clinic Liver Cancer) 0-A hepatocellular carcinoma (HCC) patients after curative resection. Materials and Methods: Preoperative sera were collected from 140 patients with BCLC 0-A HCCs undergoing curative resection during 2011-2012 in Zhongshan Hospital. Follow-up ended on November 2013. ELISA was used to detect the serum concentrations of preoperative PIVKA-II. The prognostic value of PIVKA-II and other clinicopathological factors was analyzed by the Kaplan-Meier method and the multivariate Cox proportional hazards model. Results: During follow-up, 39 of 140 patients suffered recurrence and the 1-year recurrence rate was 27.9%. The high-PIVKA-II expression group had lower 1-year time to progression (TTP) compared with the low-expression group (54.8% vs 20.2%, p<0.001). Patients with high preoperative PIVKA-II expression showed a relatively higher risk of developing postoperative recurrence than those with low expression in the low-recurrence-risk subgroups, including ${\alpha}$-fetoprotein ${\leq}400ng/mL$ (45.4% vs 16.7%; p=0.006), tumor size ${\leq}5cm$ (54.2% vs 18.1%; p<0.001), single tumor (56.0% vs 19.1%; p<0.001), absence of satellite lesions (53.3% vs 19.8%; p=0.001), absence of vascular invasion (52.6% vs 14.9%; p=0.002), and Edmondson stage I/II (60.9% vs 20.3%; p<0.001). PIVKA-II was the strongest independent prognostic factor for TTP (hazard ratio, 2.877; 95% CI 1.524-5.429; p=0.001). Conclusions: Elevated PIVKA-II is associated with early recurrence of BCLC 0-A HCC after curative resection and can be considered a novel prognostic predictor.
Somatostatin Analogues Do Not Prevent Carcinoid Crisis
Guo, Lin-Jie;Tang, Cheng-Wei 6679
Background: Carcinoid crisis is a life-threating syndrome of neuroendocrine tumors (NETs) characterized by dramatic blood pressure fluctuation, arrhythmias, and bronchospasm. In the era of booming anti-tumor therapeutics, this has become more important since associated stresses can trigger carcinoid crisis. Somatostatin analogues (SSTA) have been recommended for prophylactic administration before intervention procedures for functioning NETs. However, the efficacy is still controversial. The aim of this article is to review efficacy of SSTA for preventing carcinoid crisis. Materials and Methods: PubMed, Cochrane Controlled trials Register, and EMBASE were searched using 'carcinoid crisis' as a search term combining terms with 'somatostatin'; 'octreotide'; 'lanreotide' and 'pasireotide' until December 2013. Results: Twenty-eight articles were retrieved with a total of fifty-three unique patients identified for carcinoid crisis. The most common primary sites of NETs were the small intestine and respiratory tract. The triggering factors for carcinoid crisis included anesthesia/surgery (63.5%), interventional therapy (11.5%), radionuclide therapy (9.6%), examination (7.7%), medication (3.8%), biopsy (2%) and spontaneous (2%). No randomized controlled trials (RCTs) were identified and two case-control studies were included to assess the efficacy of SSTA for preventing carcinoid crisis by meta-analysis. The overall pooled risk of perioperative carcinoid crisis was similar despite the prophylactic administration of SSTA (OR 0.44, 95% CI: 0.14 to 1.35, p=0.15). Conclusions: SSTA wasnot helpful for preventing carcinoid crisis based on a meta-analysis of retrospective studies. Attentive monitoring and careful intervention are essential. Future studies with better quality are needed to clarify any effect of SSTA for preventing carcinoid crisis.
Diagnostic Relevance of Overexpressed Serine Threonine Tyrosine Kinase/Novel Oncogene with Kinase Domain (STYK1/NOK) mRNA in Colorectal Cancer
Orang, Ayla Valinezhad;Safaralizadeh, Reza;Hosseinpour Feizi, Mohammad Ali;Somi, Mohammad Hossein 6685
Background: Alterations in gene expression levels or mutations of tyrosine kinases are detected in some human cancers. In this study, we examined whether serine threonine tyrosine kinase 1 (STYK1)/novel oncogene with kinase domain (NOK) is overexpressed in patients with colorectal cancer. We also examined the clinical relevance of STYK1/NOK expression in cancer tissues. Materials and Methods: In tumor samples of patients with colorectal cancer and their matched non-cancerous samples, STYK1/NOK messenger RNA (mRNA) expression was analyzed by quantitative reverse transcriptase polymerase chain reaction. Associations between the expression levels of STYK1/NOK and clinicopathological characteristics of colorectal cancer were also assessed using Mann-Whitney U and Kruskal-Wallis tests. Results: Upregulation of STYK1/NOK was found in cancer tissues even at early stage of colorectal cancer compared to normal adjacent tissues. The optimal cutoff point of 0.198 the STYK1/NOK expression showed 0.78 sensitivity and 0.75 specificity for diagnosis. Overexpressed STYK1/NOK was correlated with tumor size but had no association with other clinicopathological characteristics of colorectal cancer. Conclusions: These results indicate that STYK1/NOK mRNA is widely expressed in the patients with colorectal cancer and suggest that inhibition of this molecule could potentially serve as a novel therapeutic target.
Knowledge, Attitude and Practices of Women in Maldives Related to the Risk Factors, Prevention and Early Detection of Cervical Cancer
Basu, Partha;Hassan, Salma;Fileeshia, Fathmath;Mohamed, Sizna;Nahoodha, Aminath;Shiuna, Aminath;Sulaiman, Asma Ibrahim;Najeeb, Nazeera;Saleem, Fathmath Jeehan 6691
Background: A population-based cervical cancer screening program using visual inspection with acetic acid was launched in Maldives in 2014. Our study aimed to assess the knowledge, attitude and practices of women in relation to risk factors of cervical cancer, early detection of the disease and its prevention. Materials and Methods: The questionnaire based survey was conducted among 20 to 50 year old women, systematically sampled to represent three regions of Maldives. Trained investigators interviewed a total of 2,845 women at home. Results: The prevalence of the risk factors of cervical cancer like early age at marriage and childbirth, multiple marriages, multiple marriages of the husbands, and multiple pregnancies was high. More women knew about breast cancer than cervical cancer. Even among the small number of women who knew of cervical cancer, only 34.6% had the knowledge of at least one early symptom. Very few women knew that the cancer could be prevented by any test. Only 6.2% of the women reported having ever undergone a Pap smear. Many women had the misconception that cervical cancer was infectious. In Maldives the younger women have high literacy rate due to the policy of universal free education and those with higher levels of education had improved knowledge of cervical cancer and its risk factors. The prevalence of risk factors also reduced with improved literacy. Conclusions: Awareness about risk factors and prevention of cervical cancer is limited among Maldivian women in spite of having high exposure to some of the risk factors. A universal literacy program in the country has helped to improve the knowledge of cervical cancer prevention and to reduce the exposure to various risk factors in the younger population.
Differencies in Risk Factors for Cervical Dysplasia with the Applied Diagnostic Method in Serbia
Antic, Ljiljana Gojko;Vukovic, Dejana Srboljub;Vasiljevic, Mladenko Drago;Antic, Dragan Zivojin;Aleksopulos, Hristos Georgios 6697
Background: In the etiology of cervical cancer not only HPV infection is important, but also other factors such as demographic influences andsexual and reproductive health attitudes, as well as others related to preventive measure usage (or non usage). The aim of this study was to examine factors associated with cervical dysplasia in asymptomatic women who were examined by routine cytology and cervical biopsy for early detection of cervical cancer. Materials and Methods: Socio-demographic and other characteristics were obtained from medical files of 85 examinees with pathologic cytologic findings (Pap test) and histopathologic (HP) findings after biopsy. Results: ccording to the Pap test result, a greater probability for development of cervical dysplasia was noted with examinees having a larger number of sexual partners (OR= 5.01, 95% CI 1.04-24.10), and those who are afraid of the Pap finding. Risk factors for development of cervical dysplasia according to the bioptic finding were early beginning with sexual activities, presence of any STD in personal medical history and fear of the Pap test finding. Conclusions: The only risk factor found to be important for both methods was fear of the Pap testing finding.
Influence of Propofol, Isoflurane and Enflurance on Levels of Serum Interleukin-8 and Interleukin-10 in Cancer Patients
Liu, Tie-Cheng 6703
Objective: To observe the influence of propofol, isoflurane and enflurance on interleukin-8 (IL-8) and IL-10 levels in cancer patients. Methods: Ninety cancer patients with selective operation from March 2011 to May 2014 were randomly divided into group A (34 cases), group B (28 cases) and group C (28 cases). Intramuscular injections of scopine hydrochloride and phenobarbital sodium were routinely conducted to 3 groups. After general anesthesia was induced, tracheal intubations were given. During the maintenance of anesthesia, 0.5~1.0 mg/kg propofol was intravenously injected to group A discontinuously, while continuous suctions of isoflurane and enflurance were subsequently performed to group B and C correspondingly. Clinical outcomes, postoperative complications as well as serum IL-8 and IL-10 levels before operation (T0), at the time of skin incision (T1), 3 h after the beginning of the operation (T2) and 24 h (T3) and 72 h (T4) after the operation were observed among 3 groups. Results: Operations in all groups were successfully completed. The rates of surgery associated complications were 8.82% (3/34), 7.14% (2/28) and 7.14% (2/28) in group A, B and C, respectively, and there were no significant differences (P>0.05). Serum IL-8 and IL-10 levels increased gradually from the beginning of the operation and reached the peak at T3, and were evidently higher at each time point than at T0 (P<0.01). At T1, serum IL-8 and IL-10 levels had no significant differences among 3 groups (P>0.05), but the differences were significant at T2, T3 and T4 (P<0.05). Moreover, correlation analysis suggested that serum IL-8 level was in positive relation with IL-10 level (r=0.952, P<0.01). Conclusions: Propofol, which is better in inhibiting serum IL-8 secretion and improving IL-10 secretion than isoflurane and enflurance, can be regarded as a preferable anesthetic agent in inhibiting traumatic inflammatory responses.
The AURKA Gene rs2273535 Polymorphism Contributes to Breast Carcinoma Risk - Meta-analysis of Eleven Studies
Guo, Xu-Guang;Zheng, Lei;Feng, Wei-Bo;Xia, Yong 6709
The rs2273535 polymorphism in the AURKA gene had proven to be associated with breast carcinoma susceptibility. Nevertheless, the results of different studies remain contradictory. A meta-analysis covering 28, 789 subjects from eleven different studies was here carried out in order to investigate the association in detail. The random effects model was used to analyze the pooled odds ratios (ORs) and their corresponding 95% confidence intervals (95% CIs). A significant relationship between the rs2273535 polymorphism and breast tumors was found in an allelic genetic model (OR: 1.076, 95% CI: 1.004-1.153, p=0.040, $P_{heterogeneity}$=0.002). No significant association was detected in a homozygote model (OR: 1.186, 95% CI: 0.990-1.423, P=0.065, $P_{heterogeneity}$=0.002), a heterozygote model (OR: 1.016, 95% CI: 0.959-1.076, p=0.064, $P_{heterogeneity}$=0.000), a dominant genetic model (OR: 1.147, 95% CI: 0.992-1.325, p=0.217, $P_{heterogeneity}$=0.294) and a recessive genetic model (OR: 1.093, 95% CI: 0.878-1.361, p=0.425, $P_{heterogeneity}$=0.707). A significant relationship between the rs2273535 polymorphism in the AURKA gene and breast tumor in Asian group was found in an allelic genetic model (OR: 1.124, 95% CI: 1.003-1.29, p=0.044, $P_{heterogeneity}$=0.034), a homozygote model (OR: 1.229, 95% CI: 1.038-1.455, p=0.016, $P_{heterogeneity}$=0.266) and a recessive genetic model (OR: 1.227, 95% CI: 1.001-1.504, p=0.049, $P_{heterogeneity}$=0.006). A significant association was thus observed between the rs2273535 polymorphism in the AURKA gene and breast cancer risk. Individuals with the rs2273535 polymorphism in the AURKA gene have a higher risk of breast cancer in Asian populations, but not in Caucasians.
Genetic Susceptibility to Esophageal Cancer due to CYP1A1 Gene Variant rs4646903 in Tobacco Addicted Patients of Pashtun Ethnicity: a Case Control Study in Khyber Pakhtunkhwa Province of Pakistan
Zakiullah, Zakiullah;Saeed, Muhammad;Ali, Sajid;Javed, Nabila;Khisroon, Muhammad;Muhammad, Basir;Khuda, Fazli;Ahmad, Saeed;Ismail, Mohammad 6715
The purpose of this study was to evaluate associations of the CYP1A1 gene variant rs4646903 polymorphism with the risk of developing esophageal cancer (EC). A case-control study was carried out in Pashtun population of Khyber Pakhtunkhwa province of Pakistan in which 140 hospital based EC cases and 196 population based healthy controls exposed to similar environmental conditions were included. A specific method based on the real time polymerase chain reaction (RT-PCR) was used to detect genotypes in case and control groups and results were then analyzed with SPSS version 20. In our population, individuals with CC and TC genotypes of the CYP1A1 rs4646903 polymorphism had significantly higher risk of EC (adjusted odds (OR): 15.709, 95%CI: 6.065-40.686, OR: 3.256 95%CI: 1.902-5.574 respectively). The 'C' allele was strongly associated with the disease (p< 0.0001). Adjusted OR was higher (1.5 times in C/C) in case of variant alleles that show the contribution of environmental and nutritional factors towards the development of EC. Our findings suggest that presence of the 'C' allele of rs4646903 (T>C) may be one of the risk alleles for EC susceptibility in Pashtun population.
Correlation of Tumour Response with Starting Tumour Size and Dose of Tamoxifen in an N-Methyl-N-Nitrosourea (NMU)-Induced Rat Mammary Cancer Model
Yankuzo, Hassan Muhammad;Emilia, Sharifah Tuan Sheriff;Shaari, Rumaizi;Yaacob, Nik Soriani 6721
Background: The aim of this preliminary study was to address variations of responses observed with different starting tumor sizes of 10 and 15 mm, and the effects of different doses of tamoxifen (TAM) on experimental rat mammary tumors. Materials and Methods: Thirty-five inbred female Sprague Dawley rats aged 43 days were administered with three weekly doses of N-methyl-N-nitrosourea (NMU) intraperitoneally (ip) at 50 mg/kg body weight. Animals were randomized (beginning from 10 mm tumor size) into four TAM-treated (50, 100, 200 and $500{\mu}g/day$) groups of six animals each, and another group (n=6) treated with TAM $100{\mu}g/day$ at starting tumour size of 15 mm. The animals were treated by oral gavage daily for 8 weeks before sacrifice. Results: Serum urea and creatinine, and overall physical tumor burden were significantly modulated in animals treated with variable doses of TAM compared to the untreated controls (n=5). Final body weight and tumor number were significantly different in the 10 mm-treated animals compared to those treated at 15 mm. There were no significant differences in histopathological features among all the groups. Conclusions: Our findings suggest the importance of standardizing tumour size and drug doses before initiation of treatment, particularly in the direct comparison of basic end-tumour physical parameters.
Efficacy and Safety of Docetaxel or Epirubicin, Combined with Cisplatin and Fluorouracil, (DCF and ECF) Regimens as First Line Chemotherapy for Advanced Gastric Cancer: a Retrospective Analysis from Turkey
Teker, Fatih;Yilmaz, Bahiddin;Kemal, Yasemin;Kut, Engin;Yucel, Idris 6727
Objectives: Advanced gastric cancer (AGC) patients have a poor prognosis. The best benefit of chemotherapy is usually achieved by first line setting. Very few studies have compared combination regimens. This study was designed to compare two combination regimens. Methods: Patients with advanced gastric cancer receiving first line chemotherapy were retrospectively collected, and divided into two groups, receiving DCF (docetaxel, cisplatin and fluorouracil) or ECF (epirubicin, cisplatin and fluorouracil) regimens. Data were collected for the retrospective analysis in a single center. Results: Eighty-six patients were eligible for analysis. Median overall survival (OS) was 10.0 months in the ECF group and 11.0 months in the DCF group (p=0.31). Median progression free survival (PFS) for ECF and DCF was equal at 6.0 months. Second line chemotherapy were administered in more than one third of patients. Both regimens had similar toxicity. Conclusions: This is the first study investigating the outcomes of gastric cancer chemotherapy in this region. ECF and DCF regimens have similar efficacy and a similar tolerability profile for first line treatment of advanced gastric cancer. The decision of the first line chemotherapy in advanced gastric cancer could be improved with patient selection according to clinical parameters and molecular markers.
New Technique of Intracorporeal Anastomosis and Transvaginal Specimen Extraction for Laparoscopic Sigmoid Colectomy
Wang, Zheng;Zhang, Xing-Mao;Zhou, Hai-Tao;Liang, Jian-Wei;Zhou, Zhi-Xiang 6733
Background: Despite the growing acceptance of laparoscopic colon surgery, an abdominal incision is needed to remove the specimen and perform an anastomosis. Recently, natural orifice specimen extraction (NOSE) and intracorporeal anastomosis have been proposed to minimize abdominal wall trauma and improve the quality of laparoscopic colon resections Objective: To evaluate the feasibility and safety of a new approach combining intracorporeal delta-shaped anastomosis and transvaginal specimen extraction for totally laparoscopic sigmoid colectomy. Materials and Methods: Mobilization of bowel and dissection of lymph nodes were performed laparoscopically. After both proximal and distal incisal edges about 10.0 cm distance from sigmoid neoplasm were transected with an Endoscopic Linear Cutter-Straight, a small incision about 1.0 cm was created on the each colon wall of the contralateral side of the mesentery. Then anvils of an Endoscopic Linear Cutter-Straight were inserted into each colon through the small incisions, and incision and anastomosis between the walls of each colon were performed with a linear stapler. A V-shaped anastomosis was made on the wall and the remnant openings was reclosed with the Endoscopic Linear Cutter-Straight. The culdotomy was enlarged with laparoscopic ultrasound dissector. Transvaginal extraction of specimens was accomplished through a wound protector. Results: Surgery was performed for 11 patients with sigmoid cancer. No intraoperative complications or conversions occurred. The mean operating time was 132 min. All the patients were treated laparoscopically without any postoperative complications. Conclusions: The procedures of intracorporeal delta-shaped anastomosis and transvaginal specimen extraction are safe and oncologically acceptable for selected colon cancer cases.
Suppressive Effect of Sinomenine Combined with 5-Fluorouracil on Colon Carcinoma Cell Growth
Zhang, Ji-Xiang;Yang, Zi-Rong;Wu, Dan-Dan;Song, Jia;Guo, Xu-Feng;Wang, Jing;Dong, Wei-Guo 6737
It is reported that sinomenine (SIN) and 5-fluorouracil (5-FU) both are effective for colon cancer, but their cooperative suppressive effects and toxicity remain to be clarified in detail. This study aimed to determine suppressive effects and toxicity of sinomenine (SIN) plus 5-fluorouracil (5-FU) on LoVo colon carcinoma cells in vitro and in vivo. CCK-8, Hoechst 33258 staining and an annexin V-FITC/PI apoptosis kit were used to detect suppressive effects. Western blotting was applied to investigate the essential mechanism underlying SIN and 5-FU-induced apoptosis. SIN or 5-FU or both were injected into nude mice, and then suppressive effects and side effects were observed. SIN plus 5-FU apparently inhibited the proliferation of LoVo cells and induced apoptosis. Moreover the united effects were stronger than individually (p<0.05). The results of annexin V-FITC/PI staining and Hoechst 33258 staining showed that the percentage of apoptotic cells induced by SIN and 5-FU combined or alone was significantly higher than the control group (p<0.05). Expression of Bax and Bcl-2 was up-regulated and down-regulated respectively. SIN or 5-FU significantly inhibited effects on the volume of tumour xenografts and their combined suppressive effects were stronger (p<0.05). No obvious side effects were observed. It was apparent that the united effects of SIN and 5-FU on the growth of colorectal carcinoma LoVo cells in vitro and in vivo were superior to those using them individually, and it did not markedly increase the side effects of chemotherapy.
C13orf18 and C1orf166 (MULAN) DNA Genes Methylation are Not Associated with Cervical Cancer and Precancerous Lesions of Human Papillomavirus Genotypes in Iranian Women
Sohrabi, Amir;Mirab-Samiee, Siamak;Rahnamaye-Farzami, Marjan;Rafizadeh, Mitra;Akhavan, Setareh;Hashemi-Bahremani, Mohammad;Modarressi, Mohammad Hossein 6745
Background: Nowadays, molecular biomarkers have critical roles for cancer diagnosis and prognosis in clinical laboratories. Human papillomaviruses are the main agents for etiology of cervical carcinoma. The present survey was conducted to evaluate the genes methylation in cervical cancer and precancerous lesions involvement with HPV genotypes. Materials and Methods: C13orf18 and C10rf166 (MULl or Mulan) DNA methylation as potential biomarkers and risk factors was investigated in 112 liquid based cytology and Formalin-Fixed Paraffin-Embedded tissue specimens in Iranian females with cervical intraepithelial neoplasia and dysplasia. Results: In this survey, HPV18 (61.6%) and HPV16 (42.9%) proved to be the most common HPV genotypes identified by In-House Multiplex Real Time PCR. There were no significant relationship between HPV positivity and the methylated DNA genes mentioned above (p>0.05). Conclusions: Our MethyLight data demonstrated that these genes could not be considered as specific, sensitive and suitable prognostic biomarkers in cervical dysplasia related HPV. It is suggested that further studies with more patients should be done on candidate methylated markers in different countries in order to plan for cervical cancer prevention.
Is Target Oriented Surgery Sufficient with Borderline Ovarian Tumors? - Role of Accompanying Pathologies
Gungor, Tayfun;Cetinkaya, Nilufer;Yalcin, Hakan;Ozdal, Bulent;Ozgu, Emre;Baser, Eralp;Yilmaz, Nafiye;Caglar, Mete;Zergeroglu, Sema;Erkaya, Salim 6749
Background: There are limited data in the literature related to concomitant genital or extra-genital organ pathologies in patients with borderline ovarian tumors (BOTs). The aim of this study was to evaluate our experience with 183 patients to draw attention to the accompanying organ pathologies with BOTs. Materials and Methods: One hundred eighty-three patients with BOTs, diagnosed and/or treated in our center between January of 2000 and March of 2013 were evaluated retrospectively. Data related to age, tumor histology, lesion side, disease stage, accompanying incidental ipsilateral and/or contralateral ovarian pathologies, treatment approaches, and follow-up periods were investigated. Incidental gynecologic and non-gynecologic concomitant organ pathologies were also recorded. Results: The mean age at diagnosis was 40.6 years (range: 17-78). Ninety-five patients (51%) were ${\leq}40$ years. A hundred and forty-seven patients (80%) were at stage IA of the disease. The most common type of BOT was serous in histology. Non-invasive tumor implants were diagnosed in 4% and uterine involvement was found 2% among patients who underwent hysterectomies. There were 12 patients with positive peritoneal washings. Only 17 and 84 patients respectively had concomitant ipsilateral and concomitant contralateral incidental ovarian pathologies. The most common type of uterine, appendicular and omental pathologies were chronic cervicitis, lymphoid hyperplasia and chronic inflammatory reaction. Conclusions: According to our findings most of accompanying pathologies for BOT are benign in nature. Nevertheless, there were additional malignant diseases necessitating further therapy. We emphasize the importance of the evaluation of all abdominal organs during surgery.
Demographic Risk Factors, Affected Anatomical Sites and Clinicopathological Profile for Oral Squamous Cell Carcinoma in a North Indian Population
Krishna, Akhilesh;Singh, R.K.;Singh, Shraddha;Verma, Pratima;Pal, U.S.;Tiwari, Sunita 6755
Background: Oral cancer is a common form of cancer in India, particularly among men. About 95% are squamous cell carcinomas. Tobacco along with alcohol are regarded as the major risk factors. Objectives: (i) To determine associations of oral squamous cell carcinoma (OSCC) with respect to gender, age group, socioeconomic status and risk habits; (ii) To observe the distribution of affected oral anatomical sites and clinico-pathological profile in OSCC patients. Materials and Methods: This is an unmatched case-control study during period January 2012 to December 2013. Total of 471 confirmed OSCC patients and 556 control subjects were enrolled. Data on socio-demography, risk habits with duration and medical history were recorded. Results: There were significant associations between OSCC with middle age (41-50years; unadjusted OR=1.63, 95%CI=1.05-2.52, p=0.02) (51-60 years; unadjusted OR=1.79, 95%CI=1.15-2.79, p=0.009) and male subjects (unadjusted OR=2.49, 95%CI=1.89-3.27, p=0.0001). Cases with both habits of tobacco chewing and smoking were at a higher risk for OSCC than tobacco chewing alone (unadjusted OR=0.52, 95%CI=0.38-0.72, p=0.0001), duration of risk habits also emerged as a responsible factor for the development of carcinoma. The majority of patients were presented in well-differentiated carcinomas (39.9%). Prevalence of advance stages (TNM stage III, IV) was 23.4% and 18.3% respectively. The buccal mucosa was the most common (35.5%) affected oral site. Conclusions: In most Asian countries, especially India, there is an important need to initiate the national level public awareness programs to control and prevent oral cancer by screening for early diagnosis and support a tobacco free environment.
Prognostic Value of CD44 Variant exon 6 Expression in Non-Small Cell Lung Cancer: a Meta-analysis
Zhao, Shuang;He, Jin-Lan;Qiu, Zhi-Xin;Chen, Nian-Yong;Luo, Zhuang;Chen, Bo-Jiang;Li, Wei-Min 6761
Background: CD44v6 (CD44 variant exon 6) is the chief CD44 variant isoform regulating tumor invasion, progression, and metastasis. The prognostic value of CD44v6 expression in non small cell lung cancer (NSCLC) has been evaluated in many studies, but the results have remained controversial. Thus, we performed a meta-analysis of currently available studies to investigate the prognostic value of CD44v6 expression in NSCLC patients and the relationship between the expression of CD44v6 and clinicopathological features. Materials and Methods: Two independent reviewers searched the relevant literature in Pubmed, Medline and Embase from 1946 to January 2014. Overall survival (OS) and various clinicopathological features were collected from included studies. This meta-analysis was accomplished using STATA 12.0 and Revman 5.2 software. Pooled hazard ratios (HRs) with 95% confidence intervals (95%CIs) were calculated to estimate the effects. Results: A total of 921 NSCLC patients from ten studies met the inclusion criteria. The results showed that CD44v6 high expression was a prognostic factor for poor survival (HR=1.91, 95%CI=1.12-3.26, p<0.05). With respect to clinicopathological features, CD44v6 high expression was related to histopathologic type (squamous cell carcinoma versus adenocarcinoma: OR=2.72, 95%CI=1.38-5.38, p=0.004), and lymph node metastasis (OR=3.02, 95%CI=1.93-4.72, p<0.00001). Conclusions: Our results suggested CD44v6 high expression as a poor prognostic factor for NSCLC, and CD44v6 expression is associated with lymph node metastasis and histopathologic type. Therefore, CD44v6 expression can be used as a novel prognostic marker in NSCLC cases.
Association between the MDM2 T309G Polymorphism and Leukemia Risk: a Meta-analysis
Yan, Yu-Lan;Han, Feng;Tan, Wen-Min;Wu, Cui-Ping;Qin, Xi 6767
Several studies have suggested associations between MDM2 (mouse double minute 2 homolog) polymorphisms and leukemia risk, but they reported contradictory results. For better understanding of the effect of MDM2 T309G polymorphism on leukemia risk, we performed a meta-analysis. All eligible studies were identified through a search of PubMed, Web of Science, EMBASE, and Chinese Biomedical Literature (CBM) databases before May 2014. Assessment of associations between the MDM2 T309G polymorphism and leukemia risk was conducted by odds ratios (ORs) and 95% confidence intervals (95% CIs). Finally, a total of 11 publications covering 12 case-control studies with 2, 362 cases and 5, 562 controls concerning MDM2 T309G polymorphism with respect to leukemia were included in the meta-analysis. Significant associations were found between MDM2 T309G polymorphism and leukemia risk in four models in overall populations (G vs T: OR=1.29, 95% CI=1.11-1.49, p=0.001; GG vs TT: OR=1.67, 95% CI=1.21-2.30, p=0.002; GG vs TG/TT: OR=1.56, 95% CI=1.21-2.00, p=0.001; GG/TG vs TT: OR=1.28, 95% CI=1.05-1.57, p=0.015). In the sub-group analysis according to ethnicity, increased leukemia risks were observed in three genetic models among Asians but not Caucasians. In conclusion, the results of our meta-analysis suggest that the MDM2 T309G polymorphism can increase the risk of leukemia, especially among Asian populations.
Application of Biosynthesized Silver Nanoparticles Against a Cancer Promoter Cyanobacterium, Microcystis aeruginosa
El-Sheekh, Mostafa Mohamed;El-Kassas, Hala Yassin 6773
Background: Nanotechnology opens new applications in many fields including medicine. Among all metallic nanoparticles, silver nanoparticles (silver NPS) have proved to be the most effective against a large variety of organisms including toxic cyanobacteria. Materials and Methods: Silver NPs were biosynthesized in vivo with different alga species namely, Spirulina piatensis, Chlorella vulgaris and Scenedesmus oh/iquus following two scenarios. First: by suspending a thoroughly washed algae biomass in 1 mM aqueous $AgN0_3$ solution. Second: by culturing them individually in culture media containing the same concentration of $AgN0_3$. Silver NPs were characterized using UV-Vis spectroscopy, transmission electron microscopy (TEM), energy dispersive analysis (EDX) and Fourier transform infra-red (FfIR) spectroscopy. The biosynthesized silver NPs were tested for cytotoxic activity against a cancer promoter cyanobacteruim Microcystis aeruginosa, considering effects on cell viability and chlorophyll content. Results: The surface plasmon band indicated the biosynthesis of silver NPs at ~400 nm. Transmission electron microscopy (TEM) revealed that the silver NPs had a mean average size below 100 nm. Energy-dispersive analysis X-ray (EDX) spectra confirmed the presence of silver element. FfIR spectral analyses suggested that proteins and or polysaccharides may be responsible for the biosynthesis of silver NPs and (-COO-) of carboxylate ions is responsible for stabilizing them. The toxic potentialities ofthe biosynthesized silver NPs against the cancer promoter cyanobacterium, Microcystis aeruginosa showed high reduction in viable cells count and the total chlorophyll content. Conclusions: The potential activity of the biosynthesized silver NPs from the studied algae species against Microcystis aernginosa cells is expected to be mainly mediated by the release of silver ions (Ag+) from the particle surface and bioactive compounds as indicated by FfIR analysis.
Receiver Operating Characteristic Curve Analysis of SEER Medulloblastoma and Primitive Neuroectodermal Tumor (PNET) Outcome Data: Identification and Optimization of Predictive Models
Cheung, Min Rex 6781
Purpose: This study used receiver operating characteristic curves to analyze Surveillance, Epidemiology and End Results (SEER) medulloblastoma (MB) and primitive neuroectodermal tumor (PNET) outcome data. The aim of this study was to identify and optimize predictive outcome models. Materials and Methods: Patients diagnosed from 1973 to 2009 were selected for analysis of socio-economic, staging and treatment factors available in the SEER database for MB and PNET. For the risk modeling, each factor was fitted by a generalized linear model to predict the outcome (brain cancer specific death, yes/no). The area under the receiver operating characteristic curve (ROC) was computed. Similar strata were combined to construct the most parsimonious models. A Monte Carlo algorithm was used to estimate the modeling errors. Results: There were 3,702 patients included in this study. The mean follow up time (S.D.) was 73.7 (86.2) months. Some 40% of the patients were female and the mean (S.D.) age was 16.5 (16.6) years. There were more adult MB/PNET patients listed from SEER data than pediatric and young adult patients. Only 12% of patients were staged. The SEER staging has the highest ROC (S.D.) area of 0.55 (0.05) among the factors tested. We simplified the 3-layered risk levels (local, regional, distant) to a simpler non-metastatic (I and II) versus metastatic (III) model. The ROC area (S.D.) of the 2-tiered model was 0.57 (0.04). Conclusions: ROC analysis optimized the most predictive SEER staging model. The high under staging rate may have prevented patients from selecting definitive radiotherapy after surgery.
Expression of Cyclooxygenase-2 (COX-2) in Colorectal Adenocarcinoma: an Immunohistochemical and Histopathological Study
Mahmoud, Abla Sayed;Umair, Ayesha;Azzeghaiby, Saleh Nasser;Alqahtani, Fahad Hussain;Hanouneh, Salah;Tarakji, Bassel 6787
Background: The aim of this study was to evaluate cyclooxygenase-2 (COX-2) immunoreactivity in colorectal adenocarcinomas and to find correlations with different pathological features. Materials and Methods: This study included 35 cases of colorectal carcinoma foir which surgical colectomy specimens were collected. Immunohistochemical staining of COX-2 (cyclooxygenase-2) is done by using the Streptavidin-biotin technique. Results: This work reveals that COX-2 is positive in most cases of colorectal carcinoma and negative in normal colon tissue with statistically non significant relations between COX-2 immunostaining and different pathological features. Conclusions: Our data suggest over expression of COX-2 protein in colorectal carcinoma in contrast to normal mucosa, with a possible role in cell proliferation in carcinogenesis.
Silibinin Inhibits Proliferation, Induces Apoptosis and Causes Cell Cycle Arrest in Human Gastric Cancer MGC803 Cells Via STAT3 Pathway Inhibition
Wang, Yi-Xin;Cai, Hong;Jiang, Gang;Zhou, Tian-Bao;Wu, Hai 6791
Background: To investigate the effect of silibinin on proliferation and apoptosis in human gastric cancer cell line MGC803 and its possible mechanisms. Materials and Methods: Human gastric cancer cell line MGC803 cells were treated with various concentration of silibinin. Cellular viability was assessed by CCK-8 assay andapoptosis and cell cycle distribution by flow cytometry. Protein expression and mRNA of STAT3, and cell cycle and apoptosis regulated genes were detected by Western blotting and real-time polymerase chain reaction, respectively. Results: Silibinin inhibits growth of MGC803 cells in a dose- and time-dependent manner. Silibinin effectively induces apoptosis of MGC803 cells and arrests MGC803 cells in the G2/M phase of the cell cycle, while decreasing the protein expression of p-STAT3, and of STAT3 downstream target genes including Mcl-1, Bcl-xL, survivin at both protein and mRNA levels. In addition, silibinin caused an increase in caspase 3 and caspase 9 protein as well as mRNA levels. Silibinin caused G2/M phage arrest accompanied by a decrease in CDK1 and Cyclin B1 at protein and mRNA levels.. Conclusions: These results suggest that silibinin inhibits the proliferation of MGC803 cells, and it induces apoptosis and causes cell cycle arrest by down-regulating CDK1, cyclinB1, survivin, Bcl-xl, Mcl-1 and activating caspase 3 and caspase 9, potentially via the STAT3 pathway.
Efficacy of First-line Chemotherapy Affects the Second-Line Setting Response in Patients with Advanced Non-Small Cell Lung Cancer
Cao, Wa;Li, Ai-Wu;Ren, Sheng-Xiang;Chen, Xiao-Xia;Li, Wei;Gao, Guang-Hui;He, Ya-Yi;Zhou, Cai-Cun 6799
Background: Chemotherapy is the mainstay of treatment for the majority of patients with advanced non-small cell lung cancer (NSCLC) without driver mutations and many receive therapies beyond first-line. Second-line chemotherapy has been disappointing both in terms of response rate and survival and we know relatively little about the prognostic factors. Materials and Methods: One thousand and eight patients with advanced NSCLC who received second-line chemotherapy after progression were reviewed in Shanghai Pulmonary Hospital, China, from September 2005 to July 2010. We analyzed the effects of potential prognostic factors on the outcomes of second-line chemotherapy (overall response rate, ORR; progression free survival, PFS; overall survival, OS). Results: The response and progression free survival of first-line chemotherapy affects the ORR, PFS and OS of second-line chemotherapy (ORR: CR/PR 15.4%, SD 10.1%, PD2.3%, p<0.001; PFS: CR/PR 3.80 months, SD 2.77 months, PD 2.03 months, p<0.001; OS: CR/PR 11.60 months, SD 10.33 months, PD 6.57 months, p=0.578, p<0.001, p<0.001, respectively). On multivariate analysis, better response to first-line therapy (CR/PR: HR=0.751, p=0.002; SD: HR=0.781, p=0.021) and progression within 3-6 months (HR=0.626, p<0.001), together with adenocarcinoma (HR=0.815, p=0.017), without liver metastasis (HR=0.541, p=0.001), never-smoker (HR=0.772, p=0.001), and ECOG PS 0-1 (HR=0.745, p=0.021) were predictors for good OS following second-line chemotherapy. Conclusions: Patients who responded to first-line chemotherapy had a better outcome after second-line therapy for advanced NSCLC, and the efficacy of first-line chemotherapy, period of progression, histology, liver metastasis, smoking status and ECOG PS were independent prognostic factors for OS.
Breast Cancer in Tunisia: Association of Body Mass Index with Histopathological Aspects of Tumors
Bouguerra, Hichem;Guissouma, Hajer;Labidi, Soumaya;Stambouli, Nejla;Marrakchi, Raja;Chouaib, Salem;Elgaaied, Amel Ben Ammar;Boussen, Hammouda;Gati, Asma 6805
Background: Previous studies have suggested a link between obesity and breast cancer (BC). However, there is no universal consensus, especially in population based studies. Because only few studies have been conducted on African women, we aimed here to assess the relationship between BMI at time of diagnosis and the BC histopathological features among Tunisian patients according to menopausal status using a hospital-based prospective cohort study. Materials and Methods: Clinical and pathological data were collected from 262 patients stratified on four groups according to their BMI. The relationship between BMI and histopathological features at diagnosis was analysed using univariate and multivariate analysis. Receiver-operating characteristic (ROC) curves were used to evaluate the performance of BMI in predicting of high tumor grade, in comparison to ki-67 index of proliferation. Results: Obesity was correlated with larger tumors, advanced grade and with ER-PR-Her2+ BC subtype. An association of BMI with tumor size and tumor grade was observed in both premenopausal and postmenopausal women. Additionally, a significant association between BMI and ER+, ER+PR+Her2+ and ER-PR-Her2+ status was revealed for premenopausal patients, while only ER+PR+Her2+ was associated with BMI for postmenopausal women. Finally, our results showed that compared to Ki67 proliferation index, BMI is a useful prognostic marker of high grade BC tumors. Conclusions: These data are the first to show that in Tunisia obese women suffering from BC have significantly larger tumors and advanced tumor grade and that higher BMI might influence tumor characteristics and behavior.
Development and Validation of a Breast Cancer Risk Prediction Model for Thai Women: A Cross-Sectional Study
Anothaisintawee, Thunyarat;Teerawattananon, Yot;Wiratkapun, Cholatip;Srinakarin, Jiraporn;Woodtichartpreecha, Piyanoot;Hirunpat, Siriporn;Wongwaisayawan, Sansanee;Lertsithichai, Panuwat;Kasamesup, Vijj;Thakkinstian, Ammarin 6811
Background: Breast cancer risk prediction models are widely used in clinical practice. They should be useful in identifying high risk women for screening in limited-resource countries. However, previous models showed poor performance in derived and validated settings. Therefore, we aimed to develop and validate a breast cancer risk prediction model for Thai women. Materials and Methods: This cross-sectional study consisted of derived and validation phases. Data collected at Ramathibodi and other two hospitals were used for deriving and externally validating models, respectively. Multiple logistic regression was applied to construct the model. Calibration and discrimination performances were assessed using the observed/expected ratio and concordance statistic (C-statistic), respectively. A bootstrap with 200 repetitions was applied for internal validation. Results: Age, menopausal status, body mass index, and use of oral contraceptives were significantly associated with breast cancer and were included in the model. Observed/expected ratio and C-statistic were 1.00 (95% CI: 0.82, 1.21) and 0.651 (95% CI: 0.595, 0.707), respectively. Internal validation showed good performance with a bias of 0.010 (95% CI: 0.002, 0.018) and C-statistic of 0.646(95% CI: 0.642, 0.650). The observed/expected ratio and C-statistic from external validation were 0.97 (95% CI: 0.68, 1.35) and 0.609 (95% CI: 0.511, 0.706), respectively. Risk scores were created and was stratified as low (0-0.86), low-intermediate (0.87-1.14), intermediate-high (1.15-1.52), and high-risk (1.53-3.40) groups. Conclusions: A Thai breast cancer risk prediction model was created with good calibration and fair discrimination performance. Risk stratification should aid to prioritize high risk women to receive an organized breast cancer screening program in Thailand and other limited-resource countries.
External Validation of a Clinical Scoring System for Hematuria
Lee, Seung Bae;Kim, Hyung Suk;Kim, Myong;Ku, Ja Hyeon 6819
Background: The aim of this study was to evaluate the accuracy of a new scoring system in Korean patients with hematuria at high risk of bladder cancer. Materials and Methods: A total of 319 consecutive patients presenting with painless hematuria without a history of bladder cancer were analyzed, from the period of August 2012 to February 2014. All patients underwent clinical examination, and 22 patients with incomplete data were excluded from the final validation data set. The scoring system included four clinical parameters: age (${\geq}50$ = 2 vs. <50 =1), gender (male = 2 vs. female = 1), history of smoking (smoker/ex-smoker = 4 vs. non-smoker = 2) and nature of the hematuria (gross = 6 vs. microscopic = 2). Results: The area under the receiver-operating characteristic curve (95% confidence interval) of the scoring system was 0.718 (0.655-0.777). The calibration plot demonstrated a slight underestimation of bladder cancer probability, but the model had reasonable calibration. Decision curve analysis revealed that the use of model was associated with net benefit gains over the treat-all strategy. The scoring system performed well across a wide range of threshold probabilities (15%-45%). Conclusions: The scoring system developed is a highly accurate predictive tool for patients with hematuria. Although further improvements are needed, utilization of this system may assist primary care physicians and other healthcare practitioners in determining a patient's risk of bladder cancer.
Clinical Efficacy of Endoscopic Pancreatic Drainage for Pain Relief with Malignant Pancreatic Duct Obstruction
Gao, Fei;Ma, Shuren;Zhang, Ning;Zhang, Yingchun;Ai, Meina;Wang, Bing 6823
Objective: This study was conducted to investigate the efficacy of pancreatic drainage for pain relief in advanced pancreatic cancer. Method: Seventy-one patients with pancreatic carcinoma were divided into two groups: dilated and non-dilated pancreatic ducts. All patients underwent endoscopic retrograde cholangiopancreatography (ERCP), endoscopic biliary stenting and pancreatic stenting. Visual Analog Scale (VAS) scores, pain remission rates and survival time were evaluated during follow-up. Results: The post-ERCP VAS score of the dilated group was lower than that of the non-dilated group at 1 and 3 months post-ERCP. There was no difference at 6 months. The pain remission rate in the dilated duct group was significantly higher than that in non-dilated duct group in 1 and 3 months post-ERCP. The median survival times were 8.17 and 8.22 months respectively. Conclusion: Endoscopic pancreatic drainage can relieve pain of advanced pancreatic cancer accompanied by safe dilation of the pancreatic duct.
FNC, a Novel Nucleoside Analogue, Blocks Invasion of Aggressive Non-Hodgkin Lymphoma Cell Lines Via Inhibition of the Wnt/β-Catenin Signaling Pathway
Zhang, Yan;Wang, Chen-Ping;Ding, Xi-Xi;Wang, Ning;Ma, Fang;Jiang, Jin-Hua;Wang, Qing-Duan;Chang, Jun-Biao 6829
Chemotherapy is the primary therapy for malignant lymphoma (ML). However, the clinical outcome is still far from satisfactory. Consequently, an understanding of the mechanism of modulating cancer cell invasion, migration and metastasis is important for the development of more effective chemotherapeutic agents. FNC, 2'-deoxy-2'-${\beta}$-fluoro-4'-azidocytidine, a novel cytidine analogue, has demonstrated significantly inhibitory effects on proliferation of several non-Hodgkin lymphoma (NHL) cell lines. A previous study indicated that FNC effectively inhibited the growth of Raji and JeKo-1 cells in dose-time dependent effects with $IC_{50}$ values of $0.2{\mu}M$ and $0.097{\mu}M$, respectively. This study was focused on investigating the anti-invasive properties of FNC on NHL cells and its potential mechanisms of action. Cell adhesion and transwell chamber assays were utilized to investigate the anti-invasive effects of FNC on Raji and JeKo-1 cells. Real-time PCR and Western blotting were employed to qualify the expression of ${\beta}$-catenin, the glycogen synthase kinase-3 beta (GSK-$3{\beta}$), E-cadherin vascular endothelial growth factor (VEGF), matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9). The results revealed that FNC remarkably inhibited the adhesion, migration and invasion of two human aggressive non-Hodgkin lymphoma cell lines in a dose dependent manner. Furthermore, ${\beta}$-catenin, MMP-2, MMP-9, VEGF mRNA and protein levels were decreased after FNC treatment, while GSK-$3{\beta}$ and E-cadherin increased. Our studies thus provide evidence and a rationale that FNC may offer an effective chemotherapeutic agent by regulating the invasion and metastasis of aggressive non-Hodgkin lymphoma via inhibition of the Wnt/${\beta}$-catenin signaling pathway.
Population-based Cervical Cancer Screening Using High-risk HPV DNA Test and Liquid-based Cytology in Northern Thailand
Siriaunkgul, Sumalee;Settakorn, Jongkolnee;Sukpan, Kornkanok;Srisomboon, Jatupol;Suprasert, Prapaporn;Kasatpibal, Nongyao;Khunamornpong, Surapan 6837
Background: Northern Thailand is a region with a high cervical cancer incidence. Combined high-risk HPV (hrHPV) DNA testing and cytology (co-testing) has increasingly gained acceptance for cervical cancer screening. However, to our knowledge, data from a population-based screening using co-testing have not been available in this region. This study therefore aimed to evaluate the performance of cytology and hrHPV test in women in northern Thailand. Materials and Methods: Cervical samples were collected for hybrid capture 2 (HC2) testing and liquid-based cytology from women aged 30 to 60 years who were residents in 3 prefectures of Chiang Mai in northern Thailand between May and September 2011. Women with positive cytology were referred to colposcopy, while women with positive for HC2 only were followed for 2 years. Results: Of 2,752 women included in this study, 3.0% were positive in both tests, 4.1% for HC2 only, and 1.3% had positive cytology only. At baseline screening, positive HC2 was observed in 70.6% among cytology-positive women compared with 4.3% among cytology-negative women. The prevalence of positive HC2 or cytology peaked in the age group 35-39 years and was lowest in the age group 55-60 years. High-grade squamous intraepithelial lesion or worse lesions (HSIL+) were histologically detected in 23.5% of women with positive baseline cytology and in 9.8% of women with positive baseline HC2 only on follow-up. All women with histologic HSIL+ had positive baseline HC2. Conclusions: The hrHPV test is superior to cytology in the early detection of high-grade cervical epithelial lesions. In this study, the prevalence of histologic HSIL+ on follow-up of women with positive hrHPV test was rather high, and these women should be kept under careful surveillance. In northern Thailand, hrHPV testing has a potential to be used as a primary screening test for cervical cancer with cytology applied as a triage test.
Recurrence and Metastasis of Lung Cancer Demonstrate Decreased Diffusion on Diffusion-Weighted Magnetic Resonance Imaging
Usuda, Katsuo;Sagawa, Motoyasu;Motomo, Nozomu;Ueno, Masakatsu;Tanaka, Makoto;Machida, Yuichiro;Maeda, Sumiko;Matoba, Munetaka;Tonami, Hisao;Ueda, Yoshimichi;Sakuma, Tsutomu 6843
Background: Diffusion-weighted magnetic resonance imaging (DWI) is reported to be useful for detecting malignant lesions. The purpose of this study is to clarify characteristics of imaging, detection rate and sensitivity of DWI for recurrence or metastasis of lung cancer. Methods: A total of 36 lung cancer patients with recurrence or metastasis were enrolled in this study. While 16 patients underwent magnetic resonance imaging (MRI), computed tomography (CT) and positron emission tomography-computed tomography (PET-CT), 17 underwent MRI and CT, and 3 underwent MRI and PET-CT. Results: Each recurrence or metastasis showed decreased diffusion, which was easily recognized in DWI. The detection rate for recurrence or metastasis was 100% (36/36) in DWI, 89% (17/19) in PET-CT and 82% (27/33) in CT. Detection rate of DWI was significantly higher than that of CT (p=0.0244) but not significantly higher than that of PET-CT (p=0.22). When the optimal cutoff value of the apparent diffusion coefficient value was set as $1.70{\times}10^{-3}mm^2/sec$, the sensitivity of DWI for diagnosing recurrence or metastasis of lung cancer was 95.6%. Conclusions: DWI is useful for detection of recurrence and metastasis of lung cancer.
Establishment and Partial Characterization of an Epirubicin-Resistant Gastric Cancer Cell Line with Upregulated ABCB1
Felipe, Aledson Vitor;Moraes, Andrea Aparecida;de Oliveira, Juliana;da Silva, Tiago Donizetti;Forones, Nora Manoukian 6849
Multidrug resistance (MDR) is a major impediment to successful chemotherapy of gastric cancer. Our aim was to establish an epirubicin-resistant cell subline (AGS/EPI) and to elucidate the mechanisms involved in acquired EPI resistance. The AGS/EPI cell subline developed by exposing parental AGS cells to stepwise increasing concentrations of EPI demonstrated 2.52-fold resistance relative to the AGS cell line, and mRNA expression of the ATP-dependent drug-efflux pump P-glycoprotein (Pgp), more recently known as ABCB1 protein, was similarly upregulated. An AGS/EPI cell subline could thus be effectively established, and MDR mechanism of these cells was shown to be related to the overexpression of mRNA of the ABCB1 gene.
Association between the HSPA1B ±1267A/G Polymorphism and Cancer Risk: a Meta-analysis of 14 Case-Control Studies
Kuang, Dan;Chen, Wei;Song, Yue-Zhang;Yu, Yan-Yan;Zhang, Dong-Ying;Wu, Lang;Tang, Jie 6855
Background: Previous epidemiological studies have suggested a potential role of the $HSPA1B{\pm}1267A/G$ polymorphism in risk of developing cancer. However, the results were inconsistent. Therefore, we performed this meta-analysis to summarize the possible association with cancer risk. Materials and Methods: We retrieved relevant articles from PubMed, EMBASE, ISI Web of Science, Chinese Biomedical Literature and Chinese National Knowledge Infrastructure. Studies were selected using specific criteria. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess those associations. All analyses were performed using STATA software. Results: Fourteen case-control studies, including 1, 834 cancer cases and 2, 028 controls were included in this meta-analysis. Overall, the results indicated that the G allele of HSPA1B gene ${\pm}1267A/G$ was significantly associated with an increased cancer risk in all genetic models (G vs A: OR=1.51, 95%CI 1.17-1.95, p=0.001; GG vs AA: OR=2.93, 95%CI 1.50-5.74, p=0.002; AG vs AA: OR=1.48, 95%CI 1.10-1.98, p=0.009; GG/AG vs AA: OR=1.69, 95%CI 1.22-2.33, p=0.001; GG vs AG/AA: OR=2.31, 95%CI 1.24-4.32, p=0.009). In the subgroup analysis stratified by ethnicity, a significant association was identified in Caucasians (G vs A: OR=1.35, 95%CI 1.08-1.69, p=0.008; GG/AG vs AA: OR=1.36, 95%CI 1.09-1.70, p=0.007), but not in Asians. In the stratified analysis by cancer types, individuals with the G allele showed an increased risk of hepatocellular carcinoma compared with carriers of the A allele (OR=2.40, 95%CI 1.47-3.91, p<0.001). Inversely, individuals with the GG genotype showed a decreased risk of gastric cancer compared with carriers of the AG/GG genotypes (GG vs AG/AA: OR=0.39, 95%CI 0.20-0.70, p=0.007). Conclusions: This meta-analysis suggests associations between the HSPA1B ${\pm}1267A/G$ polymorphism and risk of cancer. However, this association might be Caucasian-specific and the G allele of this polymorphism probably increases risk of hepatocellular carcinoma while decreasing risk of gastric cancer. Further well-designed studies based on larger sample sizes are needed to validate these findings.
Anti-Diabetic Medications Do Not Influence Risk of Lung Cancer in Patients with Diabetes Mellitus: a Systematic Review and Meta-analysis
Nie, Shu-Ping;Chen, Hui;Zhuang, Mao-Qiang;Lu, Ming 6863
Objectives: Several preclinical and observational studies have shown that anti-diabetic medications (ADMs) may modify the risk of lung cancer. We performed a systematic review and meta-analysis evaluating the effect of metformin, sulfonylureas (SUs), thiazolidinediones (TZDs), and insulin on the risk of lung cancer in patients with diabetes mellitus (DM). Materials and Methods: We conducted a systematic search of Pubmed and Web of Science, up to August 20, 2013. We also searched the Conference Proceedings Citation Index (CPCI) and China National Knowledge Infrastructure (CNKI) for abstracts from major meetings. Fixed or random effect pooled measures were selected based on heterogeneity among studies, which was evaluated using Q test and the I2 of Higgins and Thompson. Meta-regression was used to explore the sources of between-study heterogeneity. Publication bias was analyzed by Begg's funnel plot and Egger's regression test. Associations were assessed by odds ratios (ORs) with 95% confidence intervals (CIs). Results: A total of 15 studies (11 cohort, 4 case-control) were included in this meta-analysis. In observational studies no significant association between metformin (n=11 studies; adjusted OR=0.99, 95%CI: 0.87-1.12), SUs (n=5 studies; adjusted OR=0.98, 95%CI: 0.79-1.22), or TZDs (n=7 studies; adjusted OR=0.92, 95%CI: 0.75-1.13), insulin (n=6 studies; adjusted OR=1.13, 95%CI: 0.79-1.62) use and risk of developing lung cancer was noted. There was considerable inherent heterogeneity between studies not explained by study design, setting, or location. Conclusions: Meta-analysis of existing studies does not support a protective or harmful association between ADMs use and risk of lung cancer in patients with DM. There was considerable heterogeneity across studies, and future, well-designed, prospective studies would be required for better understanding of any association.
TP53 Polymorphisms in Sporadic North Indian Breast Cancer Patients
Sharma, Sarika;Sambyal, Vasudha;Guleria, Kamlesh;Manjari, Mridu;Sudan, Meena;Uppal, Manjit Singh;Singh, Neeti Rajan;Bansal, Darpan;Gupta, Arun 6871
Background: The purpose of this study was to evaluate the potential association of five (p.P47S, p.R72P, PIN3 Ins16bp, p.R213R and r.13494g>a) polymorphisms of TP53 with the risk of developing breast cancer in North Indian Punjabi population. Methods: We screened DNA samples of 200 sporadic breast cancer patients (197 females and 3 males) and 200 unrelated healthy, gender and age matched individuals for the polymorphisms. Results: For the p.P47S polymorphism, we observed the PP genotype in 99.5% of the patients and PS genotype in only 1 patient. All the controls had the wild type PP genotype. The frequency of RR, RP and PP genotype of p.R72P was 23.5% vs 33.5%, 51.5% vs 45.5% and 25% vs 21% in patients and controls respectively. Heterozygous (RP) genotype was increased in breast cancer patients as compared to controls (51.5 vs 45.5%) and showed 1.61 fold significantly increased risk for breast cancer (OR=1.61, 95% CI, 1.01-2.58, p=0.04). In breast cancer patients the frequencies of A1A1, A1A2 and A2A2 genotypes of PIN3 Ins16bp polymorphism were 67%, 26% and 7% respectively whereas in controls the genotype frequencies were 68.5%, 27.5% and 4% respectively, with no significant difference. For p.R213R (c.639A>G), all individuals had homozygous wild type genotype. The frequencies of GG, GA and AA genotypes of TP53 r.13494g>a polymorphism were 62 vs 67.5%, 33 vs 28% and 5 vs 4.5% in patients and controls respectively, again without significant difference. We observed that RP-A1A1 genotype combination of p.R72P and PIN3 Ins16bp and RP-GG combination of p.R72P and r.13494g>a polymorphism showed significant risk of breast cancer (OR=1.65, 95%CI: 0.98-2.78, p=0.05; OR=1.72, 95%CI: 1.01-2.92, p=0.04). Conclusion: The results of present study indicated that among the five TP53 polymorphisms investigated, the p.R72P polymorphism, and the RP-A1A1 and RP-GG genotype combination contribute to breast cancer susceptibility in North Indians.
Roles of Neutrophil/Lymphocyte and Platelet/Lymphocyte Ratios in the Early Diagnosis of Malignant Ovarian Masses
Yildirim, Mem Arjen;Seckin, Kerem Doga;Togrul, Cihan;Baser, Eralp;Karsli, Mehmet Fatih;Gungor, Tayfun;Gulerman, Hacer Cavidan 6881
Background: The present study aimed to investigate the utility and importance of the various parameters of complete blood count panel for benign-malignant differentiation of adnexal masses. Materials and Methods: This retrospective study involved 316 patients with documented benign and 253 patients with malignant adnexal masses who underwent primary surgical treatment at a tertiary referral center. Prior to the study, all benign and malignant cases were compared within their own groups and then the benign and malignant cases were compared to each other. For all cases, cut-off, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated for the neutrophil lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR), neutrophil, lymphocyte, platelet and CA-125 parameters, and the results were compared in regards to the groups. Results: NLR, PLR, neutrophil, CA-125, and platelet values were higher in the malignant compared to the benign cases (p<0.01). The lymphocyte value was lower in the malignant cases (p<0.01). No significant differences were found for basophils and eosinophils (p > 0.05). For CA-125, the sensitivity, specificity, PPV and NPV for all cases were 78%, 62%, 62% and 78%, respectively. For NLR, they were 65.6%, 72.1%, 65.3%, and 72.3%, and for PLR, 48%, 81%, 67%, and 66%. Additionally, the sensitivity and specificity were 55% and 77% for CA-125, 66% and 58% for NLR, and 61% and 58% for PLR in early malignant cases. Conclusions: NLR and PLR appear to be useful methods that can be applied together with CA-125 due to the relatively high sensitivity values for the malign-benign differentiation of ovarian masses. Although the specificity of these parameters is lower than CA-125, especially in cases with early malignant ovarian pathology, their sensitivity being higher is promising for the early diagnosis of ovarian cancer. It can be used to detect ovarian malignancies in the early stages, and it will increase the treatment options and improve survival rates.
Type-specific Prevalence of Human Papillomavirus by Cervical Cytology among Women in Brasov, Romania
Moga, Marius Alexandru;Irimie, Marius;Oanta, Alexandru;Pascu, Alina;Burtea, Victoria 6887
The oncogenic role of human papillomavirus (HPV) in triggering cervical cancer, the second most common cancer in women worldwide, is well established. Romania ranks in first place in Europe in terms of the incidence of cervical cancer. Geographical widespread data on HPV type-distribution are essential for estimating the impact of HPV vaccines and cervical cancer screening programmes. In this study we aimed to identify the prevalence of HPV genotypes and to establish correlations with abnormal cervical cytology among the female population of Brasov County, Romania. A total of 1,000 women aged 17.3-57 years, attending routine cervical examination in the Obstetrics and Gynecology Hospital of Brasov, Romania, and undergoing both cytological examination and HPV genotyping were screened. Infection with 35 different HPV genotypes was detected in 39.6% of cytological specimens. Overall HPV infections were highest in young women under 25 years (p<0.0001), in which cervical cytological abnormalities also reached the highest prevalence. Patients infected by HPV-16 or HPV-18 showed the highest prevalence of cervical cytological abnormalities. Some 48.2% of women with abnormal cytology were infected with high-risk HPV types whereas less than 3% of them were infected only with low-risk HPV types. Our study showed that the prevalence of high-risk HPV infection among Romanian women is higher compared to other studies in other geographic areas. Thus, we consider that in areas where there is an increased prevalence of high-risk HPV infections, HPV genotyping should be performed in all women aged between 18 and 45 years, and Pap test should be performed every 6 months in women with high-risk HPV infection, even those with previous normal cervical cytology.
Curcumin Analogue A501 induces G2/M Arrest and Apoptosis in Non-small Cell Lung Cancer Cells
Xia, Yi-Qun;Wei, Xiao-Yan;Li, Wu-Lan;Kanchana, Karvannan;Xu, Chao-Chao;Chen, Da-Hui;Chou, Pei-Hong;Jin, Rong;Wu, Jian-Zhang;Liang, Guang 6893
Curcumin and its analogues have been reported to exert anti-cancer activity against a variety of tumors. Here, we reported A501, a new curcumin analogue. The effect of A501 on cell viability was detected by MTT assay, the result showed that A501 had a better inhibiting effect on the four non-small cell lung cancer (NSCLC) cells than that of curcumin. Moreover, Colony forming experiment showed A501 significant restrained cell proliferation. Flow cytometry displayed A501 can cause G2/M arrest and induce apoptosis. Western blotting showed that A501 decreased the expression of cyclinB1, cdc-2, bcl-2, while increased the expression of p53, cleaved caspase-3 and bax. In conclusion, curcumin analogues A501 played antitumor activity by inhibiting cell proliferation and inducing apoptosis of NSCLC cells. And it was likely to be a promising starting point for the development of curcumin-based anticancer drugs.
Shortest Path Analyses in the Protein-Protein Interaction Network of NGAL (Neutrophil Gelatinase-associated Lipocalin) Overexpression in Esophageal Squamous Cell Carcinoma
Du, Ze-Peng;Wu, Bing-Li;Wang, Shao-Hong;Shen, Jin-Hui;Lin, Xuan-Hao;Zheng, Chun-Peng;Wu, Zhi-Yong;Qiu, Xiao-Yang;Zhan, Xiao-Fen;Xu, Li-Yan;Li, En-Min 6899
NGAL (neutrophil gelatinase-associated lipocalin) is a novel cancer-related protein involves multiple functions in many cancers and other diseases. We previously overexpressed NGAL to analyze its role in esophageal squamous cell carcinoma (ESCC). In this study, a protein-protein interaction (PPI) was constructed and the shortest paths from NGAL to transcription factors in the network were analyzed. We found 28 shortest paths from NGAL to RELA, most of them obeying the principle of extracellular to cytoplasm, then nucleus. These shortest paths were also prioritized according to their normalized intensity from the microarray by the order of interaction cascades. A systems approach was developed in this study by linking differentially expressed genes with publicly available PPI data, Gene Ontology and subcellular localizaton for the integrated analyses. These shortest paths from NGAL to DEG transcription factors or other transcription factors in the PPI network provide important clues for future experimental identification of new pathways.
Lack of Relation of Survivin Gene Expression with Survival and Surgical Prognostic Factors in Endometrial Carcinoma Patients
Aksoy, Rifat Taner;Thran, Ahmet Taner;Boran, Nurettin;Tokmak, Aytekin;Isikdogan, Betul Zuhal;Dogan, Mehmet;Thlunay, Hakki Gokhan 6905
Background: The relation ofsurvivin gene expression to survival and surgical prognostic factors in the patients with endometrial carcinoma is unclear. Materials and Methods: In this study, 62 cases who were operated due to endometrial carcinoma were investigated between 2003 and 2011 in the the gynecological oncology clinic of Female Disease Training and Investigation Hospital of Etlik Zubeyde, Hanim, Turkey. Clinical and surgical prognostic factors were investigated by screening the records of these cases. With the standard streptavidin-biotin immune peroxidase method, cytoplasmic and nuclear expression of survivin was investigated in sections with specific antibodies (1:100, diagnostic Bio Systems, USA) primer. The aim was to elucidate any relation between survivin expression and defined prognostic factors and survival. Results: There was no statistically significant relationship between cytoplasmic and nuclear indexes identified for survivin and age, body mass index, the levels of preoperative hemoglobin, platelet and Ca 125, stage, grade, lymph node meastasis, the number of meta statical lymph nodes (total, paraaortic and pelvic), myometrial invasion, serosal invasion, adnexal involvement, the presence of acid in the first diagnosis, the involvement of omentum, the adjuvant treatment application of the cases, the presence of recurrence and rate of mortality (p>0.05). Statistical significance was noted for the presence of advanced stage lymph node metastasis (pelvic, paraaortic, pelvic and paraaortic), serosal involvement, positive cytology, lymph vascular space invasion, intra abdominal metastasis, and omentum involvement. When investigated the relation between cytoplasmic and nuclear survivin indexes and total survival, the result was not statistically significant (p>0.05). Conclusions: In our study, there was no statistically significant relationship between the rates of cytoplasmic and nuclear survivin expression with identified prognostic factors and total or non-disease survival.
Activity and Expression Pattern of NF-κB/P65 in Peripheral Blood from Hepatocellular Carcinoma Patients - Link to Hypoxia Inducible Factor -1α
Gaballah, Hanaa Hibishy;Zakaria, Soha Said;Ismail, Saber Abdelrahman 6911
Background: Hepatocellular carcinoma is a complex and heterogeneous tumor with poor prognosis due to frequent intrahepatic spread and extrahepatic metastasis. The molecular mechanisms underlying HCC pathogenesis still remain obscure. Objectives: We aimed to investigate the abundance and the DNA binding activity of nuclear factor kappa B/p65 subunit in peripheral blood mononuclear cells from patients with HCC and to assess its prognostic significance and association with hypoxia inducible factor one alpha (HIF-$1{\alpha}$) in blood. Subjects and methods: This study was carried out on 40 patients classified equally into liver cirrhosis (group I) and HCC (group II), in addition to 20 healthy volunteers (group III). All groups were subjected to measurement of NF-${\kappa}B$/P65 subunit expression levels by real time-PCR, and DNA binding activity was evaluated by transcription factor binding immunoassay. Serum HIF-$1{\alpha}$ levels were estimated by enzyme-linked immunosorbent assay (ELISA). Significant increase of both the expression level and DNA binding activity of NF-${\kappa}B$/P65 subunit together with serum HIF-1 alpha levels was noted in HCC patients compared to liver cirrhosis and control subjects, with significant positive correlation with parameters for bad prognosis of HCC. In conclusion, NF-${\kappa}B$ signaling is activated in HCC and associated with disease prognosis and with high circulating levels of HIF-1 alpha.
Utility of Nuclear Morphometry in Effusion Cytology
Ambroise, Marie Moses;Jothilingam, Prabhavati;Ramdas, Anita 6919
Background: The cytological analysis of serous effusions is a common investigation and yields important diagnostic information. However, the distinction of reactive mesothelial cells from malignant cells can sometimes be difficult for the cytopathologist. Hence cost-effective ancillary methods are essential to enhance the accuracy of cytological diagnosis. The aim of this study was to examine the utility of nuclear morphometry in differentiating reactive mesothelial cells from malignant cells in effusion smears. Materials and Methods: Sixty effusion smears consisting of 30 effusions cytologically classified as malignant (adenocarcinomas) and 30 benign effusions showing reactive mesothelial cells were included in the study. ImageJ was used to measure the nuclear area, perimeter, maximal feret diameter, minimal feret diameter and the circularity. A total of ten representative cells were studied in each case. Results: Significant differences were found between benign and malignant effusions for the nuclear area, perimeter, maximal feret diameter and minimal feret diameter. No significant difference was found for circularity, a shape descriptor. Receiver operating characteristic (ROC) curve analysis revealed that nuclear area, perimeter, maximal feret diameter, and minimal feret diameter are helpful in discriminating benign and malignant effusions. Conclusions: Computerised nuclear morphometry is a helpful ancillary technique to distinguish benign and malignant effusions. ImageJ is an excellent cost effective tool with potential diagnostic utility in effusion cytology.
The CCND1 G870A Gene Polymorphism and Leukemia or Non-Hodgkin Lymphoma Risk: a Meta-analysis
Qin, Ling-Yan;Zhao, Li-Gang;Chen, Xu;Yang, Zheng;Mo, Wu-Ning 6923
In recent years, mounting evidence has indicated that the CCND1 G870A gene polymorphism, which impacts the mitotic cell cycle, may influence leukemia or non-Hodgkin lymphoma risk. Unfortunately, the previous results were inconsistent. Therefore, a meta-analysis was performed to obtain a more precise estimation of any association. We conducted a search in PubMed, Embase and CNKI covering all published papers up to March, 2014. A total of 9 publications including 10 case-control studies met the inclusion criteria. Odds ratios (ORs) and their 95% confidence intervals (95%CIs) were applied to assess association. The pooled ORs showed significant association in non-Hodgkin lymphoma (comparison A vs G: OR= 1.114, 95%CI=1.053-1.179, p=0.000; homozygote comparison AA vs GG: OR=1.245, 95%CI=1.110-1.396, p=0.000; heterozygote comparison AG vs GG: OR=1.095, 95%CI=1.000-1.199, p=0.05; dominant model AA/GA vs GG: OR=1.137, 95%CI=1.043-1.239, p=0.003; and recessive model AA vs GA/GG: OR=1.177, 95%CI=1.066-1.301, p=0.001). However, there was no association between the CCND1 G870A polymorphism and leukemia risk. In conclusion, the CCND1 G870A polymorphism may increase risk of non-Hodgkin lymphoma, but not leukemia. However, more primary large scale and well-designed studies are still required to evaluate the interaction of CCND1 G870A polymorphism with leukemia and non-Hodgkin lymphoma risk.
Epidemiological Characteristics and Prediction of Esophageal Cancer Mortality in China from 1991 to 2012
Tang, Wen-Rui;Fang, Jia-Ying;Wu, Ku-Sheng;Shi, Xiao-Jun;Luo, Jia-Yi;Lin, Kun 6929
Background: To analyze the mortality distribution of esophageal cancer in China from 1991 to 2012, to forecast the mortality in the future five years, and to provide evidence for prevention and treatment of esophageal cancer. Materials and Methods: Mortality data for esophageal cancer in China from 1991 to 2012 were used to describe its epidemiological characteristics, such as the change of the standardized mortality rate, urban-rural differences, sex and age differences. Trend-surface analysis was used to study the geographical distribution of the mortality. Curve estimation, time series, gray modeling, and joinpoint regression were used to predict the mortality for the next five years in the future. Results: In China, the incidence rate of esophageal cancer from 2007 and the mortality rate of esophageal cancer from 2008 increased yearly, with males at $8.72/10^5$ being higher than females, and the countryside at $15.5/10^5$ being higher than in the city. The mortality rate increased from age 45. Geographical analysis showed the mortality rate increased from southern to eastern China, and from northeast to central China. Conclusions: The incidence rate and the standardized mortality rate of esophageal cancer are rising. The regional disease control for esophageal cancer should be focused on eastern, central and northern regions China, and the key targets for prevention and treatment are rural men more than 45 years old. The mortality of esophageal cancer will rise in the next five years.
Association between ABCB1 Immunohistochemical Expression and Overall Survival in Gastric Cancer Patients
de Oliveira, Juliana;Felipe, Aledson Vitor;Neto, Ricardo Artigiani;Oshima, Celina Tizuko;de Souza Silva, Marcelo;Forones, Nora Manoukian 6935
Gastric cancer (GC) is one of the most common malignancies worldwide. The ABCB1 protein, a member of the ATP-binding cassette (ABC) transporter family, encoded by the ABCB1 gene, considerably influences the distribution of drugs across cell membranes as well as multidrug resistance (MDR) of antineoplastic drugs. In contrast to the extensive knowledge on the pharmacological action of ABCB1 protein, the correlation between the clinical-pathological data and ABCB1 protein expression in patients with GC remains unclear. The aim was to investigate association between ABCB1 expression and overall survival in GC patients. Human tumor fragments from 57 GC patients were examined by immunohistochemistry assay. We observed lower survival rate of patients with GC who were positive for ABCB1 expression (p=0.030). Based on these observations, we conclude that GC patients with positive ABCB1 protein immunohistochemical expression in their tumors suffer shorter overall survival.
Sulfasalazine Induces Autophagic Cell Death in Oral Cancer Cells via Akt and ERK Pathways
Han, Hye-Yeon;Kim, Hyungwoo;Jeong, Sung-Hee;Lim, Do-Seon;Ryu, Mi Heon 6939
Sulfasalazine (SSZ) is an anti-inflammatory drug that has been used to treat inflammatory bowel disease and rheumatoid arthritis for decades. Recently, some reports have suggested that SSZ also has anti-cancer properties against human tumors. However, little is known about the effects of SSZ on oral cancer. The aim of this study was to investigate the anti-cancer effects of SSZ in oral squamous cell carcinoma (OSCC) cells and to elucidate the mechanisms involved. The authors investigated the anti-proliferative effect of SSZ using the MTT method in HSC-4 cells (an OSCC cell line). Cell cycle analysis, acidic vesicular organelle (AVO) staining, monodansylcadaverine (MDC) staining and Western blotting were also conducted to investigate the cytotoxic mechanism of SSZ. SSZ significantly inhibited the proliferation of HSC-4 cells in a dose-dependent manner. In addition, SSZ induced autophagic cell death, increased microtubule-associated protein 1 light chain (MAP1-LC; also known as LC) 3-II levels, as well as induced punctate AVO and MDC staining, resulted in autophagic cell death. Furthermore, these observations were accompanied by the inhibition of the Akt pathway and the activation of ERK pathway. These results suggest that SSZ promotes autophagic cell death via Akt and ERK pathways and has chemotherapeutic potential for the treatment of oral cancer.
Evaluation of Endoscopic Characteristics of Upper Gastrointestinal Polyps in Patients with Familial Adenomatous Polyposis
Fatemi, Seyed Reza;Safaee, Azadeh;Pasha, Sara;Pourhoseingholi, Mohamad Amin;Bahrainei, Rasool;Molaei, Mahsa 6945
Background: Familial adenomatous polyposis (FAP) is a disease inherited in an autosomal dominant fashion. Most FAP patients develop upper gastrointestinal polyps; especially those in the antrum and duodenum are usually neoplastic. The aim of this study was to evaluate the prevalence of gastroduodenal polyps in Iranian FAP patients. Materials and Methods: 28 patients affected by FAP underwent front-view and side-view endoscopy. Papillary biopsies were performed in all patients. Location of polyps, their number and size, pathology study, patient general information (gender, age, family history of FAP or colorectal cancer and gastroduodenal polyps) were analyzed. Results: Gastric polyps were seen in 39.3 % of patients. Some 72.7% of the affected individuals had fundic gland polyps and 36.36% had hyperplastic polyps. Duodenal adenoma was observed in 25% of patients. While 57% of patients had tubular adenoma with low grade dysplasia, 42.8% showed tubulovillous adenoma with low grade dysplasia. Conclusions: Findings of this study indicated that the prevalence of gastroduodenal polyps in FAP patients is high and dysplasia may be evident in duodenal polyps. Therefore, it appears that routine gastroduodenal endoscopy in FAP patients is necessary.
MiRNA-15a Mediates Cell Cycle Arrest and Potentiates Apoptosis in Breast Cancer Cells by Targeting Synuclein-γ
Li, Ping;Xie, Xiao-Bing;Chen, Qian;Pang, Guo-Lian;Luo, Wan;Tu, Jian-Cheng;Zheng, Fang;Liu, Song-Mei;Han, Lu;Zhang, Jian-Kun;Luo, Xian-Yong;Zhou, Xin 6949
Background: Recent studies have indicated that microRNA-15a (miR-15a) is dysregulated in breast cancer (BC). We aimed to evaluate the expression of miR-15a in BC tissues and corresponding para-carcinoma tissues. We also focused on effects of miR-15a on cellular behavior of MDA-MB-231 and expression of its target gene synuclein-${\gamma}$ (SNCG). Materials and Methods: The expression levels of miR-15a were analysed in BC formalin fixed paraffin embedded (FFPE) tissues by microarray and quantitative real-time PCR. CCK-8 assays, cell cycle and apoptosis assays were used to explore the potential functions of miR-15a in MDA-MB-231 human BC cells. A luciferase reporter assay confirmed direct targets. Results: Downregulation of miR-15a was detected in most primary BCs. Ectopic expression of miR-15a promoted proliferation and suppressed apoptosis in vivo. Further studies indicated that miR-15a may directly interact with the 3'-untranslated region (3'-UTR) of SNCG mRNA, downregulating its mRNA and protein expression levels. SNCG expression was negatively correlated with miR-15a expression. Conclusions: MiR-15a has a critical role in mediating cell cycle arrest and promoting cell apoptosis of BC, probably by directly targeting SNCG. Thus, it may be involved in development and progression of BC.
Increased Frequency of Micronuclei in Binucleated Lymphocytes among Occupationally Pesticide-exposed Populations: A Meta-analysis
Yang, Hai-Yan;Feng, Ruo;Liu, Jing;Wang, Hai-Yu;Wang, Ya-Dong 6955
Background: The cytokinesis-block micronucleus (CBMN) assay is a standard cytogenetic tool employed to evaluate chromosomal damage subsequent to pesticide exposure. Objectives: To evaluate the pooled levels of total micronuclei (MN) and binucleated cells with micronuclei (MNC) in 1000 binucleated lymphocytes among population occupationally exposed to pesticides and further determine the more sensitive biomarker of CBMN. Materials and Methods: A meta-analysis on the pooled levels of MN and MNC in binucleated lymphocytes among occupationally pesticide-exposed populations was conducted using STATA 10.0 software and Review Manager 5.0.24 in this study. Results: We found significant differences in frequencies of MN and MNC in 1000 binucleated lymphocytes between pesticide-exposed groups and controls, and the summary estimates of weighted mean difference were 6.82 [95% confidence interval (95% CI): 4.86-8.78] and 5.08 (95% CI: 2.93-7.23), respectively. However, when we conducted sensitivity analyses further, only the MN remained statistically different, but not the MNC, the summary estimates of weight mean difference were 2.86 (95% CI: 2.51-3.21) and 0.50 (95% CI: -0.16-1.17), respectively. We also observed pesticide-exposed subjects had significantly higher MN frequencies than controls among smokers and nonsmokers, male and female populations, and American, Asian and European countries in stratified analyses. Conclusions: The frequency of MN in peripheral blood lymphocytes might be a more sensitive indicator of early genetic effects than MNC using the CBMN assay for occupationally pesticide-exposed populations.
Combined Effects of Six Cytokine Gene Polymorphisms and SNP-SNP Interactions on Hepatocellular Carcinoma Risk in Southern Guangxi, China
Bei, Chun-Hua;Bai, Hua;Yu, Hong-Ping;Yang, Yan;Liang, Qing-Qing;Deng, Ying-Ying;Tan, Sheng-Kui;Qiu, Xiao-Qiang 6961
Cytokine gene single nucleotide polymorphisms (SNPs) are involved in the genesis and progression of hepatocellular carcinoma (HCC). We hypothesized that combined effects of cytokine gene SNPs and SNP-SNP interactions are associated with HCC risk. Six SNPs in cytokine genes (IL-2, IFN-${\gamma}$, IL-$1{\beta}$, IL-6, and IL-10) were genotyped in a study of 720 Chinese HCC cases and 784 cancer-free controls. Although none of these SNPs individually had a significant effect on the risk of HCC, we found that the combined effects of these six SNPs may contribute to HCC risk (OR=1.821, 95% CI=1.078-3.075). This risk was pronounced among smokers, drinkers, and hepatitis B virus carriers. A SNP-SNP interaction between IL-2-330 and IFN-${\gamma}$-1615 was associated with an increased HCC risk (OR=1.078, 95% CI=1.022-1.136). In conclusion, combined effects of SNPs and SNP-SNP interactions in cytokine genes may contribute to HCC risk.
Epidemiological Assessment of Leukemia in Kazakhstan, 2003-2012
Igissinov, Nurbek;Kulmirzayeva, Dariyana;Moore, Malcolm A.;Igissinov, Saginbek;Baidosova, Gulnara;Akpolatova, Gulnur;Bukeyeva, Zhanar;Omralina, Yelvira 6969
Cancer is a major health problem facing the entire world, and Kazakhstan is not the exception. The aim of this study was to present an epidemiological assessment of leukemia in the population of Kazakhstan during 2003-2012. This descriptive and retrospective study was based on data obtained from all oncological organizations of the whole country. Age standardized incidence rates per 100,000 population for leukemia were calculated. Totally, 6,741 new cases of leukemia were registered in Kazakhstan during the 10 year period. The mean age of patients with leukemia was 48.5. The ASRs for leukemia among men and women were 5.3 and 3.6, respectively (p<0.001). In conclusion, our results showed a high incidence rate of leukemia in Kazakhstan, especially in the north of the country. The incidence of leukemia was significantly higher in males and increased with age. Determining and controlling important risk factors of leukemia may lead to decrease in its burden.
One-year Survival Rate of Patients with Primary Malignant Central Nervous System Tumors after Surgery in Kazakhstan
Akshulakov, Serik;Igissinov, Nurbek;Aldiyarova, Nurgul;Akhmetzhanova, Zauresh;Ryskeldiyev, Nurzhan;Auezova, Raushan;Zhukov, Yevgeniy 6973
This study was conducted to evaluate the one-year survival rate of patients with primary malignant central nervous system (CNS) tumors after surgical treatment in Kazakhstan. Retrospective data of patients undergoing operations in the Department of Central Nervous System Pathology in the JSC National Centre for Neurosurgery in the period from 2009 to 2011 were used as the research material. Kaplan-Meier survival analysis was performed with the following information: gender, date of birth, place of residence, diagnosis according to ICD-10, the date of the operation, the morphological type of tumor, clinical stage, state at the end of the first year of observation, and the date of death. The study was approved by the ethical committee of the JSC National Centre for Neurosurgery. The overall one-year overall survival rate (n=152) was 56.5% (95% confidence interval (CI): 50.2-62.7), and 79.5% (95% CI 72.2-86.8) and 33.1% (95% CI: 21.0-42.3) for Grades I-II (n=76) and Grades III-IV (n=76), respectively. Significant prognostic factors which affected the survival rate were age and higher tumor grade (Grades III-IV), corresponding with results described elsewhere in the world.
Apoptotic Effects of psiRNA-STAT3 on 4T1 Breast Cancer Cells in Vitro
Zhou, Yue;Tian, Lin;Zhang, Ying-Chao;Guo, Bao-Feng;Zhou, Qing-Wei 6977
Background: The aim of this study was to investigate the effect of a Lipofectamine2000 (Life2000) Transfection Reagent transfected psiRNA-STAT3 plasmid on 4T1 breast cancer cells. Materials and Methods: MTT was used to detect the cell proliferation of breast cancer 4T1 cells at different periods (0h, 6h, 8h, 10h); the cell cycle was assessed by flow cytometry; variation of apoptosis and mitochondrial membrane potential was observed under a fluorescence microscope; immunohistochemical staining was used to determine the expression of caspase-3 and cyclin-D1 protein. Results: An obvious effect of inhibition to 4T1 cancer cells could be observed at 8h after the psiRNA-STAT3 was transfected. Typical alterations of apoptotic morphological features were visible in the psiRNA-STAT3 treatment group. Mitochondrial membrane potential decreased significantly, the number of cells was increased in G0/G1 phase, and the number of cells was decreased in S phase, and the data were statistically significant (p<0.05), compared with the Scramble and Mock groups. Expression of caspase-3 protein was increased significantly, while that of cyclin D1 was significantly decreased. Conclusions: Life2000 transfected psiRNA-STAT3 plasmid can inhibit 4T1 tumor cell proliferation and promote apoptosis of 4T1 tumor cells, which process depends on the regulation of expression of cyclin D1 and caspase-3 protein.
Modified Toluidine Blue: an Alternative Stain for Helicobacter pylori Detection in Routine Diagnostic Use and Post-eradication Confirmation for Gastric Cancer Prevention
Sakonlaya, Dussadee;Apisarnthanarak, Anucha;Yamada, Nobutaka;Tomtitchong, Prakitpunthu 6983
Background: Modified toluidine blue staining (MTBs) is a simple, inexpensive and time saving method to detect H. pylori in gastric biopsy specimens. As a metachromatic stain, it simultaneously highlights intestinal metaplasia, a gastric cancer precancerous lesion. The aim of this study was to assess the reliability of MTBs compared with hematoxylin-eosin (H&E) for H. pylori detection using immunoperoxidase staining as the gold standard. This technique would be beneficial for a routine diagnosis and confirmation of H. pylori eradication in developing countries where endoscopic-based approaches are dominant. Materials and Methods: Esophagogastroduodenoscopy with triple site gastric biopsies was undertaken in 207 dyspeptic patients at Thammasat University Hospital, Thailand between 1997 and 1999. H&E, MTBs and immunoperoxidase staining were applied to each specimen. The presence or absence of H. pylori with each stain was interpreted separately and the sensitivity, specificity, positive and negative predictive values of H&E and MTBs were calculated. Results: A total of 282 specimens from 207 patients were evaluated. Using immunoperoxidase staining, organisms were positive in 117 specimens (41%). MTBs proved almost equally sensitive as immunoperoxidase (99%) and significantly more sensitive than H&E (85%). It has comparable specificity (96% vs 96%), PPV (95% vs 94%), and NPV (99% vs 90%) to H&E, using immunoperoxidase staining as gold standard. MTBs compared with immunoperoxidase staining, is cheaper (2 USD vs 12 USD) and faster (20 min vs 16 hrs) compared to immunoperoxidase staining. Conclusions: MTBs is effective, economical and easy to use in daily practice for the detection of H. pylori in gastric biopsy specimens. In addition to saving time in evaluating H. pylori associated gastritis, with a high sensitivity and ability to demonstrate intestinal metaplasia, the technique may have a role in confirmation of H. pylori eradication for gastric cancer prevention in a developing country setting.