Hepatocellular carcinoma (HCC) has been one of the most fatal malignant tumors worldwide and its associated morbidity and mortality remain of significant concern. Based on in-depth reviews of serological diagnosis of HCC, in addition to AFP, there are other biomarkers: Lens culinaris agglutinin-reactive AFP (AFP-L3), descarboxyprothrombin (DCP), tyrosine kinase with Ig and eprdermal growth factor (EGF) homology domains 2 (TIE2)-espressing monocytes (TEMs), glypican-3 (GPC3), Golgi protein 73 (GP73), interleukin-6 (IL-6), and squamous cell carcinoma antigen (SCCA) have been proposed as biomarkers for the early detection of HCC. The diagnosis of HCC is primarily based on noninvasive standard imaging methods, such as ultrasound (US), dynamic multiphasic multidetector-row CT (MDCT) and magnetic resonance imaging (MRI). Some experts advocate gadolinium diethyl-enetriamine pentaacetic acid (Gd-EOB-DTPA) MRI and contrast-enhanced US as the promising imaging madalities of choice. With regard to recent advancements in tissue markers, many cuting-edge technologies using genome-wide DNA microarrays, qRT-PCR, and proteomic and inmunostaining studies have been implemented in an attempt to identify markers for early diagnosis of HCC. Only less than half of HCC patients at initial diagnosis are at an early stage treatable with curative options: local ablation, surgical resection, or liver transplant. Transarterial chemoembolization (TACE) is considered the standard of care with palliation for intermediate stage HCC. Recent innovative procedures using drug-eluting-beads and radioembolization using Yttrium-90 may exhibit beneficial effects in HCC treatment. During the past few years, several molecular targeted agents have been evaluated in clinical trials in advanced HCC. Sorafenib is currently the only approved systemic treatment for HCC. It has been approved for the therapy of asymptomatic HCC patients with well-preserved liver function who are not candidates for potentially curative treatments, such as surgical resection or liver transplantation. In the USA, Europe and particularly Japan, hepatitis C virus (HCV) related HCC accounts for most liver cancer, as compared with Asia-Pacific regions, where hepatitis B virus (HBV) may play a more important role in HCC development. HBV vaccination, while a vaccine is not yet available against HCV, has been recognized as a best primary prevention method for HBV-related HCC, although in patients already infected with HBV or HCV, secondary prevention with antiviral therapy is still a reasonable strategy. In addition to HBV and HCV, attention should be paid to other relevant HCC risk factors, including nonalcoholic fatty liver disease due to obesity and diabetes, heavy alcohol consumption, and prolonged aflatoxin exposure. Interestingly, coffee and vitamin K2 have been proven to provide protective effects against HCC. Regarding tertiary prevention of HCC recurrence after surgical resection, addition of antiviral treatment has proven to be a rational strategy.

Cancer is basically a class of disorder marked by uncontrolled proliferation of cells which have the potential to interfere with different systems of body like digestive, central nervous and circulatory systems by releasing hormones. Tumors that reside only in a specified location and show restricted growth are commonly characterized as benign tumors. When tumor cells grow and effectively spread to other body parts and potentially invade and damage healthy tissues they show various degrees of malignancy. Cancer may be caused by different factors like gene mutations, carcinogens and some medical factors that harm the immune system of the body. Symptoms of cancer are relatively varied and classified according to location, progression pattern and size of tumors as well. Different diagnostic tests are used for evaluation that depends on the type of cancer. Cancer management and chemo protocols also depend on the progression and site where it develops. Cancers like breast, lung, liver, colorectal, prostate, head and neck carcinoma are most commonly diagnosed in Pakistan. This review briefly describes the three most common cancers prevailing in Pakistan and their management evaluation.

Cervical cancer is the second most common cause of cancer-related death among women worldwide, with over 500,000 new cases diagnosed annually and 50% mortality rate in Asia. In the United States, approximately 10,370 new cases of cervical cancer are diagnosed annually, and estimated 3,710 deaths occur from the disease, making it the sixth most common cause of malignancy among American women. This study aims to provide awareness about cervical cancer as well as an updated knowledge about the prevalence and incidence of cervical cancer in Asia.

Colorectal cancer (CRC) is one of most common causes of cancer-related death worldwide. Recent studies have suggested that microbial and environmental factors including diet and lifestyle can impact on colon cancer development. Vitamin D deficiency and dysfunction of vitamin D receptor (VDR) also correlate with colon cancer. Moreover, leptin, a 16-kDa polypeptide, participates in the regulation of food intake and is associated with other environmental factors affecting colon cancer through the leptin receptor. Altered levels of serum leptin and patterns of expression of its receptor (LPR) may be observed in human colon tumours. Furthermore, the collected data from in vitro and in vivo studies have indicated that consuming probiotic non-pathogenic lactic acid bacteria have beneficial effects on colon cancer. Probiotics, inflammation and vitamin D/VDR have been correlated with leptin and its receptor and are also with colon cancer. Thus, in this paper, we review recent progress on the roles of probiotic, vitamin D/VDR and leptin/LPR in inflammation and colon cancer.

Cancer stem cells (CSCs) are rare subpopulations within tumors which are recognized as culprits in cancer recurrence, drug resistance and metastasis. However, the molecular mechanisms of how CSCs are regulated remain elusive. Kr$\ddot{u}$ppel-like factors (KLFs) are evolutionarily conserved zinc finger-containing transcription factors with diverse functions in cell differentiation, proliferation, embryogenesis and pluripotency. Recent progress has highlighted the significance of KLFs, especially KLF4, in cancer and CSCs. Therefore, for better therapeutics of cancer disease, it is crucial to develop a deeper understanding of the mechanisms of how KLF4 regulate CSC functions. Herein we summarized the current understanding of the transcriptional regulation of K LF4 in CSCs, and discussed the functional implications of targeting CSCs for potential cancer therapeutics.

Several improvements in ovarian cancer treatment have been achieved in recent years, both in surgery and in combination chemotherapy with targeting. However, ovarian tumors remain the women's cancers with highest mortality rates. In this scenario, a pivotal role has been endorsed to the immunological environment and to the immunological mechanisms involved in ovarian cancer behavior. Recent evidence suggests a loss of the critical balance between immune-activating and immune-suppressing mechanisms when oncogenesis and cancer progression occur. Ovarian cancer generates a mechanism to escape the immune system by producing a highly suppressive environment. Immune-activated tumor infiltrating lymphocytes (TILs) in ovarian tumor tissue testify that the immune system is the trigger in this neoplasm. The TIL mileau has been demonstrated to be associated with better prognosis, more chemosensitivity, and more cases of optimal residual tumor achieved during primary cytoreduction. Nowadays, scientists are focusing attention on new immunologically effective tumor biomarkers in order to optimize selection of patients for recruitment in clinical trials and to identify relationships of these biomarkers with responses to immunotherapeutics. Assessing this point of view, TILs might be considered as a potent predictive immunotherapy biomarker.

Oral, cervical and breast cancers, which are either preventable and/or amenable to early detection and treatment, are the leading causes of cancer-related morbidity and mortality in India. In this paper, we describe implementation science research priorities to catalyze the prevention and control of these cancers in India. Research priorities were organized using a framework based on the implementation science literature and the World Health Organization's definition of health systems. They addressed both community-level as well as health systems-level issues. Community-level or "pull" priorities included the need to identify effective strategies to raise public awareness and understanding of cancer prevention, monitor knowledge levels, and address fear and stigma. Health systems-level or "push" and "infrastructure" priorities included dissemination of evidence-based practices, testing of point-of-care technologies for screening and diagnosis, identification of appropriate service delivery and financing models, and assessment of strategies to enhance the health workforce. Given the extent of available evidence, it is critical that cancer prevention and treatment efforts in India are accelerated. Implementation science research can generate critical insights and evidence to inform this acceleration.

Background: Previous studies evaluating the association between the xeroderma pigmentosum group G (XPG) Asp1104His polymorphism and head and neck cancer susceptibility have proven controversial. This meta-analysis of the literature was performed to obtain a more precise estimation of the relationship. Materials and Methods: We systematically searched PubMed, Embase and Web of Science with a time limit of Dec 18, 2014. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of any association. Results: We performed a meta-analysis of eight published case-control studies, including 3,621 cases and 5,475 controls. Overall, no significant association was found between the XPG Asp1104His polymorphism and head and neck cancer susceptibility under all genetic models. In the subgroup analysis by ethnicity, the XPG Asp1104His polymorphism had statistically significant association with elevated head and neck cancer risk under CC vs GG (OR=1.24, 95% CI=1.00~1.54) and the recessive model (OR=1.22, 95%CI=1.01~1.46) in Asian populations. A similar result was found under CC vs GG (OR =1.22, 95%CI=1.01~1.47) in the population based subgroup by source of control. When performed by tumor site, the XPG Asp1104His polymorphism had statistically significant association with elevated laryngeal cancer under all genetic models (CC vs GG: OR=1.59, 95% CI=1.16~2.19; GC vs GG: OR=1.38, 95%CI=1.10~1.72; dominant model: OR=1.42, 95% CI=1.15~1.74; recessive model: OR=1.36, 95% CI=1.02~1.81). Conclusions: This meta-analysis suggested that the XPG Asp1104His polymorphism is a risk factor for head and neck cancer susceptibility, especially for laryngeal cancer and in Asian populations.

We aimed to investigate the differences in health screening, including medical checkups and cancer screening, between HBV carriers and non-carriers in the Republic of Korea. In the fifth Korean National Health and Nutrition Examination Survey (KNHANES V), conducted between 2010 and 2012, 17,865 persons who answered regarding their HBV-infection status, medical checkup history, liver cancer screening and general cancer screening within the past years were included in the final analysis. In total, 295 persons were HBV carriers. Logistic regression models were used to compare the health check-up rate between the HBV carriers and non-HBV carriers. The HBV carriers were more likely to have been screened for liver cancer [adjusted odds ratio (OR): 2.83, 95% confidence interval (95%CI): 1.90-4.21] or cancer [OR: 1.44, 95%CI: 1.04-1.99]. The HBV carriers showed a probability of receiving medical checkups that was identical to that of the non-carriers [OR: 0.99, 95%CI: 0.72-1.35]. The HBV carriers, who were at higher risk of developing chronic liver disease, were more likely to be screened for cancer, including liver cancer, than the non-HBV carriers; no difference in the rate of medical checkups was observed between the HBV carriers and non-HBV carriers.

Background: Waterpipe tobacco smoking has becoming popular especially among young people worldwide. Smokers are attracted by its sweeter, smoother smoke, social ambience and the misconception of reduced harm. The objective of this study was to systematically review the effects of waterpipe tobacco policies and practices in reducing its prevalence. Materials and Methods: A systematic review was conducted electronically using the PubMed, OVID, Science Direct, Proquest and Embase databases. All possible studies from 1980 to 2013 were initially screened based on titles and abstracts. The selected articles were subjected to data extraction and quality rating. Results: Three studies met the inclusion criteria and were eligible for this review. Almost all of the waterpipe tobacco products and its accessories did not comply with the regulations on health warning labelling practices as stipulated under Article 11 of WHO FCTC. In addition, the grisly new warning labels for cigarettes introduced by Food and Drug Administration did not affect hookah tobacco smoking generally. Indoor air quality in smoking lounges was found to be poor and some hookah lounges were operated without smoke shop certification. Conclusions: Our findings revealed the availability of minimal information on the practices in controlling waterpipe smoking in reducing its prevalence. The lack of comprehensive legislations or practices in controlling waterpipe smoking warrants further research and policy initiatives to curb this burgeoning global epidemic, especially among the vulnerable younger population.

Invasion and metastasis is the major cause of tumor recurrence, difficulty for cure and low survival rate. Excavating key transcription factors, which can regulate tumor invasion and metastasis, are crucial to the development of therapeutic strategies for cancers. PU.1 is a master hematopoietic transcription factor and a vital regulator in life. Here, we report that, compared to adjacent non-cancerous tissues, expression of PU.1 mRNA in metastatic hepatocellular carcinoma (HCC), but not primary HCC, was significantly down-regulated. In addition, levels of PU.1 mRNA in metastatic hepatoma cell lines MHCC97L and MHCC97H were much lower than in non-metastatic Hep3B cells. Transwell invasion assays after PU.1 siRNA transfection showed that the invasion of hepatoma cell lines was increased markedly by PU.1 knockdown. Oppositely, overexpression of PU.1 suppressed the invasion of these cells. However, knockdown and overexpression of PU.1 did not influence proliferation. Finally, we tried to explore the potential mechanism of PU.1 suppressing hepatoma cell invasion. ChIP-qPCR analysis showed that PU.1 exhibited a high binding capacity with miR-615-5p promoter sequence. Overexpression of PU.1 caused a dramatic increase of pri-, pre- and mature miR-615-5p, as well as a marked decrease of miR-615-5p target gene IGF2. These data indicate that PU.1 inhibits invasion of human HCC through promoting miR-615-5p and suppressing IGF2. These findings improve our understanding of PU.1 regulatory roles and provided a potential target for metastatic HCC diagnosis and therapy.

To observe and analyze the characteristic trend of cancer patients hospitalized for the first time in Shanxi Tumor Hospital from 2001 to 2010, clinical data including case number, age, gender, and frequency of different tumor occurrences were collected and statistically analyzed. Results: (i) From 2001 to 2010, the number of cancer patients hospitalized for the first time increased by 1.3-fold; (ii) The patient overall average age also increased from 51.8 to 54.4, for males from 55.5 to 58.7 and females from 48.4 to 51.1, respectively. (iii) Male patients accounted for 43-48% and females accounted for 52-57% of the total. The percentage of female patients was higher than that of male patients in every year and showed an upward trend over the years, while that of the males showed a downward trend (${\chi}^2=7.031$, p=0.008); (iv) Among the top 6 most common cancers, lung, cervical, esophageal, colorectal and breast cancers tended to increase over the years (p<0.05), but not gastric cancer (p=0.423). Conclusions: (i) The number of cancer patients hospitalized for the first time during the past 10 years increased year by year, and was higher for female than male; (ii) the average age of patients increased year after year and was greater for male than female; (iii) the number of patients with lung cancer, cervical cancer, esophageal cancer, colorectal cancer and breast cancer increased over years.

Abnormally expressed microRNAs (miRNAs) and genes have been found to play key roles in esophageal squamous cell carcinoma (ESCC), but little is known about the underlying mechanisms. The aim of this paper was to assess inter-relationships and the regulatory mechanisms of ESCC through a network-based approach. We built three regulatory networks: an abnormally expressed network, a related network and a global network. Unlike previous examples, containing information only on genes or miRNAs, the prime focus was on relationships. It is worth noting that abnormally expressed network emerged as a fault map of ESCC. Theoretically, ESCC might be treated and prevented by correcting the included errors. In addition, the predicted transcription factors (TFs) obtained by the P-match method also warrant further study. Our results may further guide gene therapy researchers in the study of ESCC.

Background: Low-dose oral contraceptives (OC) were approved by the Japanese Ministry of Health, Labor and Welfare in 1999, yet despite their contraceptive and non-contraceptive health benefits, only 5% of the target population use them. Fear of increased cancer risk, particularly breast cancer, is one reason for this. Due to low OC uptake and low screening participation, a paucity of data is available on the risk of OC use and breast cancer in Japanese women. The present study investigated OC use and breast cancer risk, as well as menstrual, reproductive and family factors. Materials and Methods: This was a clinic-based case-control study of women aged 20-69yrs who had undergone breast screening between January 2007 and December 2013 in central Tokyo. In all, 28.8% of the participants had experience with OC use. Cases were 155 women with a pathologically confirmed diagnosis of breast cancer. Controls were the remaining 12,333 women. Results: Increased age was a significant risk factor for breast cancer (p<0.001). A lower risk was found in premenopausal women presently taking OC compared to never users (OR 0.45; 95% CI 0.22-0.90) after adjusting for age, parity and breast feeding, and a family history of breast cancer. Conclusions: Increased age rather than OC use had a greater effect on breast cancer risk. This risk may be decreased in premenopausal women with OC use, but further long-term prospective studies are necessary.

Background: Cancer loci comprise heterogeneous cell populations with diverse cellular secretions. Therefore, disseminating cancer-specific or cancer-associated protein antigens from tissue lysates could only be marginally correct, if otherwise not validated against precise standards. Materials and Methods: In this study, 2DE proteomic profiles were examined from lysates of 13 lung-adenocarcinoma tissue samples and matched against the A549 cell line proteome. A549 matched-cancer-specific hits were analyzed and characterized by MALDI-TOF/MS. Results: Comparative analysis identified a total of 13 protein spots with differential expression. These proteins were found to be involved in critical cellular functions regulating pyrimidine metabolism, pentose phosphate pathway and integrin signaling. Gene ontology based analysis classified majority of protein hits responsible for metabolic processes. Among these, only a single non-predictive protein spot was found to be a cancer cell specific hit, identified as Armadillo repeat-containing protein 8 (ARMC8). Pathway reconstruction studies showed that ARMC8 lies at the centre of cancer metabolic pathways. Conclusions: The findings in this report are suggestive of a regulatory role of ARMC8 in control of proliferation and differentiation in lung adenocarcinomas.

Background: Cholangiocarcinoma (CHCA) is serious public health problem in Thailand, especially in the northeastern and northern regions. CHCA is known as one of the most aggressive malignant tumors associated with local invasion and a high rate of metastasis. A crucial step in the invasion process is the proteolytic degradation of the extracellular matrix (ECM) and basal membranes, for which several studies have shown a critical role played by matrix metalloproteinase-11 (MMP-11). Objective: This study aim to detect MMP-11 expression in CHCA specimens and any correlation with survival time. Materials and Methods: A retrospective analysis was conducted of 30 patients with CHCA in Rajvithi hospital, who had undergone immunohistochemical staining of MMP-11. Relationships between clinicopathological data and MMP-11 expression in CHCA specimens were analyzed by the ${\chi}^2$ test or Fisher's exact test. The estimated survival and the survival differences were analyzed by the Kaplan-Meier method and the log-rank test, respectively. Results: MMP-11 expression was found in 15 specimens (50%). The overall mean survival time is 237.0 days (95% CI 135.4-338.5, SD 271.9). Specimens with a positive MMP-11 had an average survival time of 136.7 days (95%CI 50.3-223.1, SD 156.0). Survival differences was signficant for the positive and negative MMP-11(p=0.022), but not well differentiated tumor and moderate to poor differentiated tumor (p=0.755), CA19-9 level of >1,000 and <1,000 (p=0.488), and between advanced and non-advanced staging (p=0.388). Conclusions: The positive MMP-11 expression indicates poor prognosis in CHCA specimens.

Background: The neutrophil-to-lymphocyte ratio (NLR) is a strong predictor of mortality in patients with colorectal, lung, gastric cancer, pancreatic and metastatic renal cell carcinoma. We here evaluated whether preoperative NLR is an independent prognostic factor for non-metastatic renal cell carcinoma (RCC). Materials and Methods: Data from 327 patients who underwent curative or palliative nephrectomy were evaluated retrospectively. In preoperative blood routine examination, neutrophils and lymphocytes were obtained. The predictive value of NLR for non-metastatic RCC was analyzed. Results: The NLR of 327 patients was $2.72{\pm}2.25$. NLR <1.7 and NLR ${\geq}1.7$ were classified as low and high NLR groups, respectively. Chi-square test showed that the preoperative NLR was significantly correlated with the tumor size (P=0.025), but not with the histological subtype (P=0.095)and the pT stage (P=0.283). Overall survival (OS) and disease-free survival (DFS) were assessed using the Kaplan-Meier method. Effects of NLR on OS (P=0.007) and DFS (P=0.011) were significant. To evaluate the independent prognostic significance of NLR, multivariate COX regression models were applied and identified increased NLR as an independent prognostic factor for OS (P=0.015), and DFS (P=0.019). Conclusions: Regarding patient survival, an increased NLR represented an independent risk factor, which might reflect a higher risk for severe cardiovascular and other comorbidities. An elevated blood NLR may be a biomarker of poor OS and DFS in patients with non-metastatic RCC.

Background: Many factors, including molecular ones, were demonstrated to be associated with long-term prognosis of hepatocellular carcinoma (HCC). Thus far, the expression and clinicopathologic and prognostic significance of the carboxyl terminus of Hsp70-interacting protein (CHIP) in B-type hepatitis virus (HBV)-related HCC remain unknown. Materials and Methods: CHIP expression was detected by immunohistochemical staining of surgical samples from 79 patients with HCC with HBsAg positivity. In addition, correlations with clinicopathologic parameters and patient survival were evaluated. Results: It was found that positive CHIP staining was observed in tumor, but not non-tumor, tissues. High expression of CHIP was significantly related to larger tumor size, with marginally significant associations noted for presence of portal vein invasion and higher serum a-fetoprotein level. In addition, univariate analysis showed that high CHIP expression was a powerful predictor for dismal overall and disease-free survival. However, independent prognostic implications of CHIP were not proven in multivariate Cox regression test. Conclusions: CHIP is overexpressed in HBV-related HCC and is associated with unfavorable biological behavior as well as poor prognosis. However, its prognostic role needs to be further validated.

Leukemia is a clonal disorder with blocked normal differentiation and cell death of hematopoietic progenitor cells. Traditional modalities with most used radiation and chemotherapy are nonspecific and toxic which cause adverse effects on normal cells. Differentiation inducing therapy forcing malignant cells to undergo terminal differentiation has been proven to be a promising strategy. However, there is still scarce of potent differentiation inducing agents. We show here that Angelica sinensis polysaccharide (ASP), a major active component in Dong quai (Chinese Angelica sinensis), has potential differentiation inducing activity in human chronic erythro-megakaryoblastic leukemia K562 cells. MTT assays and flow cytometric analysis demonstrated that ASP inhibited K562 cell proliferation and arrested the cell cycle at the G0/G1 phase. ASP also triggered K562 cells to undergo erythroid differentiaton as revealed by morphological changes, intensive benzidine staining and hemoglobin colorimetric reaction, as well as increased expression of glycophorin A (GPA) protein. ASP induced redistribution of STAT5 protein from the cytoplasm to the nucleus. Western blotting analysis further identified that ASP markedly sensitized K562 cells to exogenous erythropoietin (EPO) by activating EPO-induced JAK2/STAT5 tyrosine phosphorylation, thus augmenting the EPO-mediated JAK2/STAT5 signaling pathway. On the basis of these findings, we propose that ASP might be developed as a potential candidate for chronic myelogenous leukemia inducing differentiation treatment.

The p53 tumor suppressor protein is a principal mediator of growth arrest, senescence, and apoptosis in response to a broad array of cellular damage. p53 is a substrate for the ubiquitin-proteasome system, however, the ubiquitin-conjugating enzymes (E2s) involved in p53 ubiquitination have not been well studied. UBE2Q1 is a novel E2 ubiquitin conjugating enzyme gene. Here, we investigated the effect of UBE2Q1 overexpression on the level of p53 in the MDA-MB-468 breast cancer cell line as well as the interaction between UBE2Q1 and p53. By using a lipofection method, the p53 mutated breast cancer cell line, MDA-MB-468, was transfected with the vector pCMV6-AN-GFP, containing UBE2Q1 ORF. Western blot analysis was employed to verify the overexpression of UBE2Q1 in MDA-MB-468 cells and to evaluate the expression level of p53 before and after cell transfection. Immunoprecipitation and GST pull-down protocols were used to investigate the binding of UBE2Q1 to p53. We established MDA-MB-468 cells that transiently expressed a GFP fusion proteins containing UBE2Q1 (GFP-UBE2Q1). Western blot analysis revealed that levels of p53 were markedly lower in UBE2Q1 transfected MDA-MB-468 cells as compared with control MDA-MB-468 cells. Both in vivo and in vitro data showed that UBE2Q1 co-precipitated with p53 protein. Our data for the first time showed that overexpression of UBE2Q1can lead to the repression of p53 in MDA-MB-468 cells. This repression of p53 may be due to its UBE2Q1 mediated ubiquitination and subsequent proteasome degradation, a process that may involve direct interaction of UBE2Q1with p53.

Background: Although cervical cancer is preventable and early screening might decrease the associated mortality, challenges faced by the women and health care providers can postpone early detection. This qualitative study aimed to establish patient and provider perceptions about personal and socio-cultural barriers for cervical cancer screening in Mashhad, Iran. Materials and Methods: In the present study, which was conducted in 2012, eighteen participants, who were selected purposefully, participated in individual in-depth, semi-structured interviews, which were recorded, transcribed verbatim, and analyzed using conventional content analysis and Atlas-Ti software. Results: One theme and two categories were derived from data including: cognitive/behavioral factors (lack of a community-based approach to cervical cancer, lack of awareness, wrong attitude and lack of health seeking behaviors) and socio/cultural issues (socio-cultural invasion, mismatch between tradition, modernity and religious, extra marital relationships and cultural taboos). Conclusions: Providing community based approach education programs and employing social policy are needed for preventing of cervical cancer in Iran.

Context: Insulin-like growth factor peptides play important roles in regulating cell growth, cell differentiation, and apoptosis, and have been demonstrated to promote the development of colorectal cancer (CRC). Objective: To examine the association of insulin-related biomarkers including insulin-like growth factor-1 (IGF-1), insulin-like growth factor binding protein-3 (IGFBP-3) and C-peptide with CRC risk and assess their relevance in predictive models. Materials and Methods: The odds ratios of colorectal cancer for serum levels of IGF-1, IGFBP-3 and C-peptide were estimated using unconditional logistic regression models in 100 colorectal cancer cases and 100 control subjects. Areas under the receiving curve (AUC) and integrated discrimination improvement (IDI) statistics were used to assess the discriminatory potential of the models. Results: Serum levels of IGF-1 and IGFBP-3 were negatively associated with colorectal cancer risk (OR=0.07, 95%CI: 0.03-0.16, P for trend <.01, OR=0.06, 95%CI: 0.03-0.15, P for trend <.01 respectively) and serum C-peptide was positively associated with risk of colorectal cancer (OR=4.38, 95%CI: 2.13-9.06, P for trend <.01). Compared to the risk model, prediction for the risk of colorectal cancer had substantially improved when all selected biomarkers IGF-1, IGFBP-3 and inverse value of C-peptide were simultaneously included inthe reference model [P for AUC improvement was 0.02 and the combined IDI reached 0.166% (95 % CI; 0.114-0.219)]. Conclusions: The results provide evidence for an association of insulin-related biomarkers with colorectal cancer risk and point to consideration as candidate predictor markers.

Background: A moderate dose of radiation is the recommended treatment for solitary plasmacytoma (SP), but there is controversy over the role of surgery. Our study aimed at comparing different treatment modalities in the management of SP. Materials and Methods: Data from 38 consecutive patients with solitary plasmacytoma, including 16 with bone plasmacytoma and 22 with extramedullary plasmacytoma, were retrospectively reviewed. 15 patients received radiotherapy alone; 11 received surgery alone, and 12 received both. The median radiation dose was 50Gy. All operations were performed as radical resections. Local progression-free survival (LPFS), multiple myeloma-free survival (MMFS), progression-free survival (PFS) and overall survival (OS) were calculated and outcomes of different therapies were compared. Results: The median follow-up time was 55 months. 5-year LPFS, MMFS, PFS and OS were 87.0%, 80.9%, 69.8% and 87.4%, respectively. Univariate analysis revealed, compared with surgery alone, radiotherapy alone was associated with significantly higher 5-year LPFS (100% vs 69.3%, p=0.016), MMFS (100% vs 51.4%, p=0.006), PFS (100% vs 33.7%, p=0.0004) and OS (100% vs 70%, p=0.041). Conclusions: Radiotherapy alone can be considered as a more effective treatment for SP over surgery. Whether a combination of radiotherapy and surgery improves outcomes requires further study.

Background: Colorectal cancer is one of the most commonly occurring cancers in China. Dietary fibre has been thought to decrease the risk of colorectal cancer in Western countries. However, studies investigating the association between dietary fibre (particularly soluble and insoluble fibres) and colorectal cancer have hitherto been lacking in China. Objective: This case-control study examined the effect of dietary fibre intake on the risk of colorectal cancer, stratified by tumour site. Materials and Methods: The study included 265 cases (colon cancer, 105; rectal cancer, 144; colon and rectal cancer, 16) and 252 controls residing in Qingdao. A food frequency questionnaire that included 121 food items was used to collect dietary information. Odds ratio (OR) and 95% confidence intervals (CI) were calculated using unconditional logistic regression analysis. Results: For food groups, controls in the study consumed more vegetables, soy food and total fibre than did colorectal cancer patients (p<0.05). The intakes of fruit, meat and sea-food did not differ significantly between cases and controls. However, we did not find any association between soy food intake and colon cancer. We observed inverse associations between total fibre intake and colorectal, colon and rectal cancer (Q4 vs Q1: OR=0.44, 95%CI, 0.27-0.73; OR=0.40, 95%CI, 0.21-0.76; OR=0.52, 95%CI, 0.29-0.91). Vegetable fibre intake showed similar inverse associations (Q4 vs Q1: OR=0.51, 95%CI, 0.31-0.85; OR=0.48, 95%CI, 0.25-0.91; OR=0.53, 95%CI, 0.29-0.97). In addition, inverse associations were observed between soluble fibre and insoluble fibre and both colorectal cancer and colon cancer. No relationship was found between colorectal cancer and fruit, soy or grain fibre intakewhen the results were stratified by tumour site. Conclusions: The present study suggests that vegetable fibre and total fibre play very important roles in protecting against colorectal cancer. Soluble and insoluble fibres were inversely associated with only colorectal cancer and colon cancer.

Background: Polymeric nanoparticles are attractive materials that have been widely used in medicine for drug delivery, with therapeutic applications. In our study, polymeric nanoparticles and the anticancer drug, chrysin, were encapsulated into poly (D, L-lactic-co-glycolic acid) poly (ethylene glycol) (PLGA-PEG) nanoparticles for local treatment. Materials and Methods: PLGA: PEG triblock copolymers were synthesized by ring-opening polymerization of D, L-lactide and glycolide as an initiator. The bulk properties of these copolymers were characterized using 1H nuclear magnetic resonance spectroscopy and Fourier transform infrared spectroscopy. In addition, the resulting particles were characterized by scanning electron microscopy. Results: The chrysin encapsulation efficiency achieved for polymeric nanoparticles was 70% control of release kinetics. The cytotoxicity of different concentration of pure chrysin and chrysin loaded in PLGA-PEG ($5-640{\mu}M$) on T47-D breast cancer cell line was analyzed by MTT-assay. Conclusions: There is potential for use of these nanoparticles for biomedical applications. Future work should include in vivo investigation of the targeting capability and effectiveness of these nanoparticles in the treatment of breast cancer.

Background: Approaches in disruption of MDM2-p53 interactions have now emerged as an important therapeutic strategy in resurrecting wild type p53 functional status. The present study highlights virtual screening strategies in identification of high affinity small molecule non-peptidic inhibitors. Nutlin3A and RG7112 belonging to compound class of Cis-imidazoline, MI219 of Spiro-oxindole class and Benzodiazepine derived TDP 665759 served as query small molecules for similarity search with a threshold of 95%. The query molecules and the similar molecules corresponding to each query were docked at the transactivation binding cleft of MDM2 protein. Aided by MolDock algorithm, high affinity compound against MDM2 was retrieved. Patch Dock supervised Protein-Protein interactions were established between MDM2 and ligand (query and similar) bound and free states of p53. Compounds with PubCid 68870345, 77819398, 71132874, and 11952782 respectively structurally similar to Nutlin3A, RG7112, Mi219 and TDP 665759 demonstrated higher affinity to MDM2 in comparison to their parent compounds. Evident from the protein-protein interaction studies, all the similar compounds except for 77819398 (similar to RG 7112) showed appreciable inhibitory potential. Of particular relevance, compound 68870345 akin to Nutlin 3A had highest inhibitory potential that respectively showed 1.3, 1.2, 1.16 and 1.26 folds higher inhibitory potential than Nutilin 3A, MI 219, RG 7112 and TDP 1665759. Compound 68870345 was further mapped for structure based pharamacophoric features. In the study, we report Cis-imidazoline derivative compound; Pubcid: 68870345 to have highest inhibitory potential in blocking MDM2-p53 interactions hitherto discovered.

Background: Lynch syndrome (LS) is an inherited predisposition to colorectal, endometrial (uterine) and other cancers. Although most cancers are not inherited, about 5 percent (%) of people who have colorectal or endometrial cancer have the Lynch syndrome. It involves the alteration of mismatch repair (MMR) genes; MLH1, MSH2, MSH6 or PMS2. In this study, we analyzed the expression of MMR proteins in colorectal cancer in a Malay cohort by immunohistochemistry. Materials and Methods: A total of 17 patients were selected fulfilling one of the Bethesda criteria: colorectal cancer diagnosed in a patient aged less than 50 years old, having synchronous and metachronous colorectal cancer or with a strong family history. Immunohistochemical staining was performed on paraffin embedded tumour tissue samples using four antibodies: MLH1, MSH2, MSH6 and PMS2. Results: Twelve out of 17 patients (70.6%) were noted to have a family history. A total of 41% (n=7) of the patients had abnormal immunohistochemical staining with one or more of the four antibodies. Loss of expression were noted in 13 tumour tissues with a negative staining score <4. Of 13 tumour tissues, four showed loss expression of MLH1. For PMS2, loss of expression were noted in five cases. Both MSH2 and MSH6 showed loss of expression in two tumour tissues respectively. Conclusions: Revised Bethesda criteria and immunohistochemical analysis constituted a convenient approach and is recommended to be a first-line screening for Lynch syndrome in Malay cohorts.

Background: This study aimed to establish a nomogram by combining clinicopathologic factors with overall survival of stage IA-IIB cervical cancer patients after complete resection with pelvic lymphadenectomy. Materials and Methods: This nomogram was based on a retrospective study on 1,563 stage IA-IIB cervical cancer patients who underwent complete resection and lymphadenectomy from 2002 to 2008. The nomogram was constructed based on multivariate analysis using Cox proportional hazard regression. The accuracy and discriminative ability of the nomogram were measured by concordance index (C-index) and calibration curve. Results: Multivariate analysis identified lymph node metastasis (LNM), lymph-vascular space invasion (LVSI), stromal invasion, parametrial invasion, tumor diameter and histology as independent prognostic factors associated with cervical cancer survival. These factors were selected for construction of the nomogram. The C-index of the nomogram was 0.71 (95% CI, 0.65 to 0.77), and calibration of the nomogram showed good agreement between the 5-year predicted survival and the actual observation. Conclusions: We developed a nomogram predicting 5-year overall survival of surgically treated stage IA-IIB cervical cancer patients. More comprehensive information that is provided by this nomogram could provide further insight into personalized therapy selection.

Dietary prevention has been known to reduce breast cancer risk. Sesamin is one of the major components in sesame seeds and has been widely studied and proven to have anti-proliferation and anti-angiogenic effects on cancer cells. In this study, the influence of sesamin was tested in the human breast cancer MCF-7 cell line for cell viability (MTT assay) and cell cycling (flow cytometry). Results showed that sesamin dose-dependently (1, 10 and $50{\mu}M$) reduced the cell viability and increased LDH release and apoptosis (TUNEL assay). In addition, there was a significant increase of sub-G1 phase arrest in the cell cycle after sesamin treatment. Furthermore, sesamin increased the expression of apoptotic markers of Bax, caspase-3, and cell cycle control proteins, p53 and checkpoint kinase 2. Taken together, these results suggested that sesamin might be used as a dietary supplement f or prevention of breast cancer by modulating apoptotic signal pathways and inhibiting tumor cell growth.

The CCAAT/enhancer-binding protein-alpha (CEBPA) is a transcriptional factor that plays a crucial role in the control of proliferation and differentiation of myeloid precursors. This gene was recognized as the target of genetic alterations and were associated with clinical complexity among AML. We here analyze the frequency and types of CEBPA mutations and polymorphisms in a de novo AML patients from South India and tried to find out associations of these variations with different clinical parameters and the prognostic significance in AML. Study was carried out in 248 de novo AML patients, cytogenetic analysis was performed from the bone marrow samples and was karyotyped. PCR-SSCP analysis and sequencing was performed for the detection of CEBPA gene variations. All the statistical analysis was performed using SPSS 17 (statistical package for social sciences) software. Pearson Chi-square test, Mann-Whitney U test, Kaplan-Meier survival analysis and log rank tests were performed. CEBPA mutations were detected in 18% and CEBPA polymorphisms were detected in 18.9% of AML cases studied. Most of the mutations occured at the C terminal region. Polymorphisms were detected in both N and C terminal region. with most common being, c.584_589dup ACCCGC and c.690G>T. A significant association was not observed for the mutation and polymorphism with respect to clinical and laboratory parameters. Survival advantage was observed for the mutated cases compared to non mutated cases, especially for the normal karyotype groups. Polymorphisms has no effect on the survival pattern of AML patients. CEBPA mutation and polymorphisms were observed with similar frequency and was identified in all the FAB subtypes as well as in cytogenetic risk groups in our study population, but CEBPA mutations alone confer a prognostic value for NK AML patients.

Background: Chronic myeloid leukemia (CML) is a myeloproliferative disorder of pluripotent stem cells, caused by reciprocal translocation between the long arms of chromosomes 9 and 22, t(9;22)(q34;q11), known as the Philadelphia chromosome. Materials and Methods: A total of 51 CML patients were recruited in this study. Complete blood counts of all CML patients were performed to find out their total leukocytes, hemoglobin and platelets. FISH was performed for the detection of BCR-ABL fusion and cryptogenic tests using bone marrow samples were performed for the conformation of Ph (9;22)(q34;q11) and variant translocation mechanisms. Results: In cytogenetic analysis we observed that out of 51 CML patients 40 (88.9%) were Ph positive and 4 (8.88%) had Ph negative chromosomes. Mean values of WBC 134.5 $10^3/{\mu}l$, hemoglobin 10.44 mg/dl, and platelets 288.6 $10^3/{\mu}l$ were observed in this study. Conclusions: In this study, Ph positive translocation between chromosome (9:22)(q34;q11) were observed in 40 (88.9%) CML patients.

Background: The Functional Assessment of Cancer Therapy - Breast (FACT-B) scale is widely used to measure health-related quality of life in cancer patients. The aim of the present study is to validate the FACT-B in a sample of Iranian women with breast cancer. Materials and Methods: The sample consisted of 300 women selected through non-random convenient sampling procedure from oncology hospitals and clinics in Kermanshah and Shiraz cities. They were asked to fill in the Persian versions of the FACT-B scale, Hospital Anxiety and Depression Scale, the European Organization for Research and Treatment of Cancer quality of life EORTC QLQ30. Confirmatory factorial analysis of the methods, concurrent validity and discriminant, and Cronbach's alpha for internal consistency were applied. Results: Internal consistency using Cronbach's alpha was 0.63 to 0.93 for the subscales and 0.92 for the total scale. Significant correlations between FACT-B and other measures indicate that this scale had concurrent and discriminant validity. The values of fit indices were satisfactory. Conclusions: The Persian version of the FACT-B scale is valid and reliable and, therefore, the scale can be used in research and clinical settings to assess health-related quality of life in Iranian patients with breast cancer.

Arsenic trioxide (ATO) has been found to exert anti-cancer activity in various human malignancies. However, the molecular mechanisms by which ATO inhibits tumorigenesis are not fully elucidated. In the current study, we explored the molecular basis of ATO-mediated tumor growth inhibition in pancreatic cancer cells. We used multiple approaches such as MTT assay, wound healing assay, Transwell invasion assay, annexin V-FITC, cell cycle analysis, RT-PCR and Western blotting to achieve our goal. We found that ATO treatment effectively caused cell growth inhibition, suppressed clonogenic potential and induced G2-M cell cycle arrest and apoptosis in pancreatic cancer cells. Moreover, we observed a significant down-regulation of Skp2 after treatment with ATO. Furthermore, we revealed that ATO regulated Skp2 downstream genes such as FOXO1 and p53. These findings demonstrate that inhibition of Skp2 could be a novel strategy for the treatment of pancreatic cancer by ATO.

Background: Hairy and enhancer of split 1 (Hes-1) protein is a downstream target of Notch signaling and is a basic helix-loop-helix transcriptional repressor. However, definitive evidence for a role in hepatocellular carcinoma (HCC) cells has not been reported. Here, Hes-1 was revealed to an important component of the Notch signaling cascade in HCC cell lines possessing different potential for lung metastasis. Materials and Methods: RNAi mediated by plasmid constructs was used to analyze the role of Hes-1 in MHCC-97L HCC cells by assessing proliferation, apoptosis, cell migration and matrigel invasion following transfection. Hes-1 protein expression analysis in HCC tissue was also conducted by immunohistochemistry. Results: Our studies revealed that Hes-1 was decreased in HCC cell lines with higher lung metastasis potential at both the mRNA and protein levels. Down-regulation of the Hes-1 gene in MHCC-97L cells resulted in increased cell proliferation, reduced apoptosis and increased migration and invasion. Conclusions: Hes-1 has potential prognostic value in post-surgical HCC patients and may be an independent prognostic indicator for overall survival and tumor recurrence. These findings have important implications for understanding the mechanisms by which Hes-1 participates in tumor proliferation and invasion.

Background: The human protein methyl-transferase DOT1L catalyzes the methylation of histone H3 on lysine 79 (H3K79) at homeobox genes and is also involved in a number of significant processes ranging from gene expression to DNA-damage response and cell cycle progression. Inhibition of DOT1L activity by shRNA or small-molecule inhibitors has been established to prevent proliferation of various MLL-rearranged leukemia cells in vitro, establishing DOT1L an attractive therapeutic target for mixed lineage leukemia (MLL). Most of the drugs currently in use for the MLL treatment are reported to have low efficacy, hence this study focused on various natural compounds which exhibit minimal toxic effects and high efficacy for the target receptor. Materials and Methods: Structures of human protein methyl-transferase DOT1L and natural compound databases were downloaded from various sources. Virtual screening, molecular docking, dynamics simulation and drug likeness studies were performed for those natural compounds to evaluate and analyze their anti-cancer activity. Results: The top five screened compounds possessing good binding affinity were identified as potential high affinity inhibitors against DOT1L's active site. The top ranking molecule amongst the screened ligands had a Glide g-score of -10.940 kcal/mol and Glide e-model score of -86.011 with 5 hydrogen bonds and 12 hydrophobic contacts. This ligand's behaviour also showed consistency during the simulation of protein-ligand complex for 20000 ps, which is indicative of its stability in the receptor pocket. Conclusions: The ligand obtained out of this screening study can be considered as a potential inhibitor for DOT1L and further can be treated as a lead for the drug designing pipeline.

Background: Positive para-aortic lymph node (PALN) at diagnosis in cervical cancer patients confers an unfavorable prognosis. This study reviewed the outcomes of extended field radiotherapy (EFRT) and concurrent chemotherapy with extended field RT (CCEFRT) in patients with positive PALN at diagnosis. Materials and Methods: Medical records of 407 cervical cancer patients between 1st January 2002 to 31st December 2012 were reviewed. Some 32 cases with positive PALN were identified to have received definitive extended field radiotherapy with or without chemotherapy. Treatment outcomes, clinicopathological factors affecting survival and radiotherapy related acute and late effects were analyzed. Results: Totals of 13 and 19 patients underwent EFRT and CCEFRT respectively during the period of review. The median follow-up was 70 months. The 5-year overall survival (OS) was 40% for patients who underwent CCEFRT as compared to 18% for patients who had EFRT alone, with median survival sof 29 months and 13 months, respectively. The 5-years progression free survival (PFS) for patients who underwent CCEFRT was 32% and 18% for those who had EFRT. Median PFS were 18 months and 12 months, respectively. Overall treatment time (OTT) less than 8 weeks reduced risk of death by 81% (HR=0.19). Acute side effects were documented in 69.7% and 89.5% of patients who underwent EFRT and CCEFRT, respectively. Four patients (12.5%) developed radiotherapy late toxicity and there was no treatment-related death observed. Conclusions: CCEFRT is associated with higher 5-years OS and median OS compared to EFRT and with tolerable level of acute and late toxicities in selected patients with cervical cancer and PALN metastasis.

Objective: To evaluate the diagnostic performance of IOTA simple rules in predicting malignant adnexal tumors by non-expert examiners. Materials and Methods: Five obstetric/gynecologic residents, who had never performed gynecologic ultrasound examination by themselves before, were trained for IOTA simple rules by an experienced examiner. One trained resident performed ultrasound examinations including IOTA simple rules on 100 women, who were scheduled for surgery due to ovarian masses, within 24 hours of surgery. The gold standard diagnosis was based on pathological or operative findings. The five-trained residents performed IOTA simple rules on 30 patients for evaluation of inter-observer variability. Results: A total of 100 patients underwent ultrasound examination for the IOTA simple rules. Of them, IOTA simple rules could be applied in 94 (94%) masses including 71 (71.0%) benign masses and 29 (29.0%) malignant masses. The diagnostic performance of IOTA simple rules showed sensitivity of 89.3% (95%CI, 77.8%; 100.7%), specificity 83.3% (95%CI, 74.3%; 92.3%). Inter-observer variability was analyzed using Cohen's kappa coefficient. Kappa indices of the four pairs of raters are 0.713-0.884 (0.722, 0.827, 0.713, and 0.884). Conclusions: IOTA simple rules have high diagnostic performance in discriminating adnexal masses even when are applied by non-expert sonographers, though a training course may be required. Nevertheless, they should be further tested by a greater number of general practitioners before widely use.

Background: This pooled analysis was conducted to evaluate the efficacy and safety of pemetrexed based chemotherapy in treating patients with metastatic bladder cancer as salvage chemotherapy. Methods: Clinical studies evaluating the efficacy and safety of pemetrexed based regimens on response and safety for patients with bladder cancer were identified by using a predefined search strategy. Pooled response rate (RR) of treatment were calculated. Results: In pemetrexed based regimens, 3 clinical studies which including 105 patients with advanced transitional cell cancer of the urothelium were considered eligible for inclusion. Pooled analysis suggested that, in all patients, pooled RR was 26.7% (28/105) for pemetrexed based regimens. Major adverse effects were neutropenia, anorexia, fatigue, and anemia in pemetrexed based treatment. Two treatment related deaths occurred with pemetrexed based treatment. Conclusion: This pooled analysis suggests that pemetrexed based regimens are associated with mild activity and good tolerability in treating patients with metastatic bladder cancer.

Background: Cervical cancer is the second most common cause of cancer related death of women. Persistent HPV infection, especially with high-risk types such as HPV16 and HPV18, has been identified to be the primary cause of cervical cancer. E6 and E7 are the major oncoproteins of high-risk HPVs, which are expressed exclusively in HPV infected tissues, and thereby represent ideal therapeutic targets for immunotherapy of cervical cancer. Materials and Methods: In this work, we used recombinant adenovirus expressing coden-optimized HPV16 E6 and E7 fusion protein (Ad-ofE6E7) to prime dendritic cells (DC-ofE6E7), to investigate the ability of primed DC vaccine in eliciting antitumor immunity in vitro and vivo. Results: Our results indicated that DC-ofE6E7 vaccine co-culturing with splenocytes could strongly induce a tumor-specific cytotoxic T lymphocyte (CTL) response and kill the TC-1 cells effectively in vitro. Moreover, DC-ofE6E7 vaccine induced protective immunity against the challenge of TC-1 cancer cells in vivo. Conclusions: The results suggested that the HPV16 ofE6E7 primed DC vaccine has potential application for cervical cancer immunotherapy.

Background: Cholangiocarcinoma (CCA), or bile duct cancer, is incurable with a high mortality rate due to a lack of effective early diagnosis and treatment. Identifying cytoplasmic membrane proteins of invasive CCA that facilitate cancer progression would contribute toward the development of novel tumor markers and effective chemotherapy. Materials and Methods: An invasive CCA cell line (KKU-100) was stimulated using TNF-${\alpha}$ and then biotinylated and purified for mass spectrometry analysis. Novel proteins expressed were selected and their mRNAs expression levels were determined by real-time RT-PCR. In addition, the expression of ALCAM was selected for further observation by Western blot analysis, immunofluorescent imaging, and antibody neutralization assay. Results: After comparing the proteomics profile of TNF-${\alpha}$ induced invasive with non-treated control cells, over-expression of seven novel proteins was observed in the cytoplasmic membrane of TNF-${\alpha}$ stimulated CCA cells. Among these, ALCAM is a novel candidate which showed significant higher mRNA- and protein levels. Immunofluorescent assay also supported that ALCAM was expressed on the cell membrane of the cancer, with increasing intensity associated with TNF-${\alpha}$. Conclusions: This study indicated that ALCAM may be a novel protein candidate expressed on cytoplasmic membranes of invasive CCA cells that could be used as a biomarker for development of diagnosis, prognosis, and drug or antibody-based targeted therapies in the future.

Background: Recent studies revealed a relationship between ground-glass opacity (GGO) ratio on computed tomography (CT) and serum carcinoembryonic antigen (CEA) level in lung adenocarcinoma. Since an association between lepidic histologic pattern and GGO is well accepted, we investigated the link between histologic subtype and serum CEA level in resected lung adenocarcinoma. Materials and Methods: One hundred and eighty-one consecutive patients with resected lung adenocarcinoma were studied retrospectively. The histologic subtype was subdivided into 2 groups: lepidic dominant histologic subtype, including adenocarcinoma in situ, minimally invasive adenocarcinoma and lepidic predominant invasive adenocarcinoma versus other subtypes. Results: The 5-year survival of patients with s high serum CEA level was significantly more unfavorable than that with normal levels. Similarly, there was also a relationship between the patient survival and histologic subtype, with favorable survival found in patients with the lepidic dominant histologic subtype. There was a significant relationship between serum CEA level and lepidic dominant histologic subtype overall and in p-stage I patients. Conclusions: Lung adenocarcinomas with non-lepidic dominant histologic subtype are associated with high serum CEA levels.

Background: The aim of this study was to analyze the patterns of relapse and survival outcomes in Northern Thai women with recurrent endometrial cancer (EC). Materials and Methods: Medical records were abstracted from EC patients who underwent primary surgery from 1999 to 2012. Data on clinicopathologic variables, sites of first recurrence, time to relapse of disease, and overall survival (OS) was analyzed. Associations between the clinicopathological variables and the rates of disease recurrence were determined. Results: Among 1,204 reviewed records, 42 eligible patients were identified with recurrent disease. The median age was 55 years and the median follow-up time was 26.0 months. The median times to recurrence (TTR) after completion of the initial treatment in the group of local relapse (LR) and distant/combined sites of recurrence (DCSR) was 6.6 (95% CI=4.6 to 8.6 months) and 16.9 months (95% CI=5.6 to 28.2 months), respectively (p=0.36). The 2-year survival and 3-year survival probability in the group of LR was 54.2% (95% CI=27.2 to 81.3%) and 34.7% (95% CI=9.2 to 60.2%), compared to 50.4% (95% CI=41.1 to 59.7%) and 42.1% (95%CI= 24.1 to 60.1%) for those with DCSR. Distant recurrence was the most frequent pattern of relapse. Overall survival was not significantly different in patients with local relapse when compared to those with DCSR (p=0.69). Conclusions: Patients with recurrence of EC after primary treatment had a worse prognosis and clinical aggressiveness. LR and DCSR occurred most during the first three years. The common sites of relapses were vaginal cuff, pelvis, and lungs. No significant clinicopathological predictor for survival outcomes was identified.

Background: To explore whether combined detection of serum tumor markers (CEA, CA72-4, CA19-9 and TSGF) improve the sensitivity and accuracy in the diagnosis of gastric cancer (GC). Materials and Methods: An automatic chemiluminescence immune analyzer with matched kits were used to determine the levels of serum CEA, CA72-4, CA19-9 and TSGF in 45 patients with gastric cancer (GC group), 40 patients with gastric benign diseases (GBD group) hospitalized in the same period and 30 healthy people undergoing a physical examination. The values of those 4 tumor markers in the diagnosis of gastric cancer was analyzed. Results: The levels of serum CEA, CA72-4, CA19-9 and TSGF of the GC group were higher than those of the GBD group and healthy examined people and the differences were significant (P<0.001). The area under receiver operating characteristic (ROC) curves for single detection of CEA, CA72-4, CA19-9 and TSGF in the diagnosis of GC was 0.833, 0.805, 0.810 and 0.839, respectively. The optimal cutoff values for these 4 indices were 2.36 ng/mL, 3.06 U/mL, 5.72 U/mL and 60.7 U/mL, respectively. With combined detection of tumor markers, the diagnostic power of those 4 indices was best, with an area under the ROC curve of 0.913 (95%CI 0.866~0.985), a sensitivity of 88.9% and a diagnostic accuracy of 90.4%. Conclusions: Combined detection of serum CEA, CA72-4, CA19-9 and TSGF increases the sensitivity and accuracy in diagnosis of GC, so it can be regarded as the important means for early diagnosis.

Objective: To investigate any association of the miRNA146a rs2910164 C>G polymorphism with head and neck cancer risk. Materials and Methods: The Medline, PubMed, PUBMED, EMBASE, Web of Science, WanFang and CNKI databases were searched and a meta-analysis was conducted using RevMan 5.2 software. Results: After searching and evaluating the literature, a total seven papers involving 2,766 patients with head and neck cancer and 6,603 healthy controls were included into this meta analysis. The results showed that there were no significant differences between patients and healthy controls overall for the miRNA rs2910164 C>G gene polymorphism (dominant model:OR=0.78, 95%CI:0.58-1.04, P=0.09; recessive model:OR=0.86, 95%CI:0.67-1.12, P=0.27;GG:CC:OR=0.75, 95%CI:0.52-1.08, P=0.12;GC:CC:OR=0.79, 95%CI:0.60-1.04, P=0.10). However, a significant association of miRNA rs2910164 C>G gene polymorphism with Chinese head and neck cancer risk was noted, limited to the dominant model (OR=0.68, 95%CI:0.50-0.95, P=0.02;GG:CC:OR=0.62, 95%CI:0.42-0.92, P=0.02;GC:CC:OR=0.72, 95%CI:0.520.99, P=0.04). Conclusions: miRNA146a rs2910164 C>G polymorphism is not associated with head and neck cancer risk in general, but tehre may be link in Chinese.

Background: The neutrophil/lymphocyte ratio (NLR) is a simple index of systemic inflammatory response, and has been shown to be a prognostic indicator in some types of cancer. Inflammation has been implicated in the initiation and progression of thyroid cancer. The aim of this study was to examine the relationship of NLR with papillary thyroid cancer (PTC) and different benign thyroid pathologies like multinodular goiter (MNG) and lymphocytic thyroiditis (LT). Materials and Methods: We retrospectively evaluated the neutrophil, lymphocyte counts and NLR calculated from these parameters of 232 patients with histologically confirmed as multinodular goiter (group MNG) (n=70), lymphocytic thyroiditis (group LT) (n=97), LT with PTC (group LT-PTC) (n=25) and PTC (group PTC) (n=40). The optimal cut-off value for NLR was determined. Results: NLR level was significantly higher in groups LT-PTC and PTC as compared to groups MNG and LT (p<0.05). NLR of LT subgroups according to TSH levels were not different (p>0.05). When we grouped the patients as benign and malignant according to PTC presence, the optimum NLR cut-off point obtained from ROC analysis was 1.91 (sensitivity 89.0% and specificity 54.5%). Conclusions: Since NLR was significantly elevated in group LT-PTC and group PTC, NLR value may give an opinion as a potential marker in differentiation of benign and malign thyroid disorders. For this purpose a cut-off value of 1.91 for NLR may be accepted.

Obesity markedly increases the risk of colorectal cancer. Recently, the preventive effects of edible mushrooms on triglyceride elevation and visceral fat accumulation have been reported. Here, the effects of Pleurotus eryngii (Eringi) and Hypsizygus marmoreus (Bunashimeji) on azoxymethane (AOM)-induced aberrant crypt foci (ACF; precancerous lesions) in the colorectums of mice fed a high-fat diet were examined. Eringi (ER) and Bunashimeji (BU) mushroom powder samples were used. Six-week-old male C57BL/6J mice received an intraperitoneal injection of AOM (10 mg/kg) once a week for two weeks, and were sacrificed and dissected at 6 weeks after the start of the experiment. After the initiation of the experiment, they received a normal diet (ND), high-fat diet (HFD), HFD + ER (1 or 5% of diet), or HFD + BU (1 or 5% of diet). As a result, body and fat weights were significantly lower in the 5% ER and BU groups than in the HFD group. Liver triglyceride levels were also significantly lower in the 5% ER and BU groups. Total liver cholesterol levels were significantly lower in the 5% ER group. The numbers of ACF (especially large ACF) showed strong inhibitory effects in both ER and BU groups. Measurement of the cell proliferation marker Ki-67 labeling index in the colonic mucosa demonstrated more significant suppression in both ER and BU groups than in the HFD group. These results suggest that the simultaneous intake of ER and BU may inhibit colorectal tumorigenesis in HFD-fed mice.

Aloe-emodin (1, 8-dihydroxy-3-hydroxyl-methylanthraquinone; AE) and emodin (1,3,8-trihydroxy-6-methylanthraquinone; EM) are anthraquinone derivatives that have been detected in some medical plants and share similar anthraquinone structures. AE and EM have been shown to exhibit anticancer activities in various cancer cell lines; however, the inhibitory effects of these derivatives on the growth of cancer cells were previously reported to be different. Gastric cancer is the second most common cause of cancer cell death worldwide. In the present study, we examined the inhibitory effects of 0.05 mM AE and 0.05 mM EM on the proliferation of the MKN45 human gastric cancer cell line. The proliferation of MKN45 cells was significantly inhibited in AE- and EM-treated groups 24 h and 48 h after treatment. Furthermore, the inhibitory effects of EM were stronger than those of AE. The cell cycle of MKN45 cells were arrested in G0/G1 phase or G0/G1 and G2/M phases by AE and EM, respectively. However, an analysis of intracellular polyamine levels and DNA fragmentation revealed that the mechanisms underlying cell death following cell arrest induced by AE and EM differed.

It's known that having multiple sexual partners is one of the risk factors of human papillomavirus (HPV) infection which is a major cause of cervical cancer. However, it is not clear whether the number of sexual partners is an independent risk factor for cervical cancer. We identified relevant studies by searching the databases of MEDLINE, PubMed and ScienceDirect published in English from January 1980 to January 2014. We analyzed those studies by combining the study-specific odds ratios (ORs) using random-effects models. Forty-one studies were included in this meta-analysis. We observed that the number of sexual partners was associated with the occurrence of non-malignant cervical disease (OR=1.82, 95%CI 1.63-2.00) and invasive cervical carcinoma (OR=1.77, 95%CI 1.50-2.05). Subgroup analyses revealed that the association remained significant after controlling for HPV infection (OR=1.52, 95%CI 1.21-1.83 for non-malignant disease; OR=1.53, 95%CI 1.30-1.76 for invasive cervical carcinoma). We found that there was a non-linear relation of the number of sexual partners with both non-malignant cervical disease and invasive cervical carcinoma. The risk of both malignant and non-malignant disease is relatively stable in women with more than 4-7 sexual partners. Furthermore, the frequency-risk of disease remained significant after controlling for HPV infection.The study suggested that h aving multiple sexual partners, with or without HPV infection, is a potential risk factor of cervical cancer.

Objective: Our aim was to investigation the roles of MHC class I chain-related gene A(MICA) and natural killer cell group 2D(NKG2D) in human renal cancer cells. Materials and Methods: The expression of membrane MICA (mMICA) on renal cells and NKG2D on NK cells were detected by flow cytometry (FCM); the content of sMICA were detected by enzyme linked immunosorbent assay (ELISA) and the distribution of mMICA on renal tumor tissues by immunohistochemistry; the interaction between MICA and NKG2D was observed by antibody closed method. Results: Our results showed that the expression of mMICA in renal cancer tissues was significantly higher than in controls, where the soluble MICA was not expressed. Cytotoxic activity of NK cells was significantly reduced after exposure to NKG2D and MICA antibodies (P<0.05), and serum containing sMICA can obviously lower the function of NKG2D (P<0.05). Conclusions: The interaction of mMICA and NKG2D play important roles in mediation of cytotoxicity of NK cells in RCC. On the other hand, sMICA may mediate tumor immune escape through down- regulated NKG2D expression.

Purpose: To investigate the antitumor activity and mechanism of chloroquine (CQ) in combination with cisplatin (DDP) in nude mice xenografted with gastric cancer SGC7901 cells. Materials and Methods: 35 cases of gastric cancer patients with malignant ascites were enrolled and intraperitoneal cisplatin injection was performed. Ascites were collected before and 5 days after perfusion for assessment of autophagy levels in cancer cells. In addition, 24 tumor-bearing mice were randomly divided into control, DDP, CQ and CQ + DDP groups. Results: In 54.3% (19/35) of patients the treatment was therapeutically effective (OR), 5 days after peritoneal chemotherapy, 13 patients had the decreased ascites Beclin-1 mRNA levels. In 16 patients who had NR, only 2 cases had decreased Beclin-1 (P=0.001). Compared with the control group, the xenograft growth in nude mice in the DDP group was low, and the inhibition rate was 47.6%. In combination with chloroquine, the inhibition rate increased to 84.7% (P<0.01). The LC3-II/I ratio, and Beclin1 and MDR1/P-gp expression were decreased, while caspase 3 protein levels increased (P<0.05). Conclusions: Antitumor ability of cisplatin was associated with autophagy activity and chloroquine can enhance chemosensitivity to cisplatin in gastric cancer xenografts nude mice.

Objective: To evaluate the efficacy of mannatide combined with sodium cantharidate vitamin B6 in the treatment of malignant pleural effusions. Materials and Methods: Data for 69 patients with malignant pleural effusions who did not receive systemic chemotherapy were collected. Injection into the thorax using mannatide combined with sodium cantharidate vitamin B6 was performed for 37 patients in the experimental group and mannatide combined with cisplatin for 32 patients in the control group. Objective responses, KPS (Karnofsky Scoring) and incidences of side effects between the two groups were compared. Results: 13 patients reached CR (complete response) and 11 PR (partial response) in the experimental group, while 12 patients reached CR and 9 PR in the control group, the difference in overall objective responses between the two groups not being significant (66.7% vs 63.6%, p=0.806). However, improvement of KPS in the experimental group wasgreater than in the control group; total side-effect incidences during the period of treatment were 22.2% (8/36) and 54.5% (18/33), respectively (p=0.006). Conclusions: Regimen of mannatide combined with sodium cantharidate vitamin B6 had better improvement in quality-of-life and symptom relief, with a lower side-effect incidence in treatment of malignant pleural effusions.

Curcumin, a lipid-soluble compound extracted from the plant Curcuma Longa, has been found to exert immunomodulatory effects via macrophages. However, most studies focus on the low bioavailability issue of curcumin by nano and microparticles, and thus the role of macrophages in the anticancer mechanism of curcumin has received little attention so far. We have previously shown the potential biocompatibility, biodegradability and anti-cancer effects of dendrosomal curcumin (DNC). In this study, twenty-seven BALB/c mice were equally divided into control as well as 40 and 80 mg/kg groups of DNC to investigate the involvement of macrophages in the antitumor effects of curcumin in a typical animal model of metastatic breast cancer. At the end of intervention, the tumor volume and weight were significantly reduced in DNC groups compared to control (P<0.05). Histopathological data showed the presence of macrophages in tumor and spleen tissues. Real-time PCR results showed that DNC increased the expression of STAT4 and IL-12 genes in tumor and spleen tissues in comparison with control (P<0.05), referring to the high levels of M1 macrophages. Furthermore treatment with DNC decreased STAT3, IL-10 and arginase I gene expression (P<0.05), indicating low levels of M2 macrophage. The results confirm the role of macrophages in the protective effects of dendrosomal curcumin against metastatic breast cancer in mice.

Background: Lung cancer is a fatal malignancy with high mortality and short survival time. The aim of this study was to estimate survival rates of Iranian patients with lung cancer and its associate predictive factors. Materials and Methods: The study was conducted on 355 patients admitted to hospitals of West Azerbaijan in the year 2007. The patients were followed up by phone calls until the end of June 2014. The survival rate was estimated using the Kaplan-Meier method and log-rank test for comparison. The Cox's proportional hazard model was used to investigate the effect of various variables on patient survival time, including age, sex, Eastern Cooperative Oncology Group (ECOG) performance, smoking status, tumor type, tumor stage, treatment, metastasis, and blood hemoglobin concentration. Results: Of the 355 patients under study, 240 died and 115 were censored. The mean and median survival time of patients was 13 and 4.8 months, respectively. According to the results of Kaplan-Meier method, 1, 2, and 3 years survival rates were 39%, 18%, and 0.07%, respectively. Based on Cox regression analysis, the risk of death was associated with ECOG group V (1.83, 95% CI: 1 Conclusions: The survival time of the patients with lung cancer is very short. While early diagnosis may improve the life expectancy effective treatment is not available.

Background: Colorectal cancer (CRC) is the most common gastrointestinal cancer and the incidence is increasing in many developing countries. While it can be detected early and even prevented through screening and removal of premalignant lesions, there are barriers to screening which include low level of knowledge and awareness of CRC. This study assessed the level of knowledge of CRC in Brunei Darussalam. Materials and Methods: A total of 431 (262 male and 161 female) subjects participated in this questionnaire study. Subjects were scored on their knowledge of signs/symptoms (maximum 10 correct answers) and known risk factors for CRC (maximum 10 correct answers) and were categorised into poor (0-2), moderate (3-4) and satisfactory (5-10). Comparisons were made between the various patient factors. Results: Overall, 54.1% could not name any CRC signs/symptoms or associated risk factors. Most were not aware of any screening modalities. The overall scores for CRC signs/symptoms and risk factors were $1.3{\pm}1.39$ (range 0-6) and $0.6{\pm}1.05$ (range 0-5) respectively. Overall, the breakdown of scores was: poor (78.1%), moderate (20.3%) and satisfactory (6.2%) for signs/symptoms and poor (93.2%), moderate (6.2%) and satisfactory (0.7%) for risk factors. Higher level of education, female gender and non-Malay race were associated with higher scores for both signs/symptoms and knowledge of screening modality; however the overall scores were low. Conclusions: Our study showed that the general knowledge of CRC in Brunei Darussalam is poor. Being female, with higher levels of education and non-Malay race were associated with higher scores, but they were still generally poor. More needs to be done to increase the public knowledge and awareness of CRC.

Fatty liver disease (FLD) can be a precondition for other liver pathology including cholangiocarcinoma (CCA). Diabetes mellitus (DM) has been suggested in some studies to be a risk factor for FLD as well as cancers, including cholangiocellular carcinoma; however, there are currently very few studies on FLD in DM subjects, although the rate of FLD continues to increase annually. To determine the association between DM and FLD ultrasonographic data were analyzed from the Cholangiocarcinoma Screening and Care Program (CASCAP), in northeast Thailand. DM was reported by the subjects based on the CASCAP health questionnaire. Factors that were associated with FLD were determined by prevalence, odds ratio (ORs) and its 95% confidence intervals (CIs) using multiple logistic regression. There were 45,263 subjects with a mean age of 53.46 (${\pm}9.25$) years. FLD was found in 36.3% of DM subjects but only in 20.7% of non-DM subjects. The association between DM and FLD was adjusted for all other factors including gender, age, education level, relatives diagnosed with CCA, smoking, alcohol consumption, and hepatitis B and C. The risk of DM in subjects having FLD was highly significant compared with the non-DM subjects (OR 2.13; 95%CI: 1.92 to 2.35; p-value < 0.001). Thus DM is significantly associated with FLD which in turn may facilitate the development of several diseases including CCA. DM should be taken into consideration in future ultrasonic investigations of FLD and CCA.

Background: Pancreatic cancer risk is increased in patients with type 2 diabetes, while being reduced by metformin treatment. However, it is unclear whether metformin could be associated with clinical outcomes of patients with pancreatic cancer and concurrent type 2 diabetes. Materials and Methods: A pooled analysis of 4 publications including 1,429 patients was performed to investigate the association of metformin and overall survival(OS) in patients with pancreatic cancer and concurrent type 2 diabetes. Results: A borderline significant relative survival benefit was found in metformin treated patients compared with non-metformin treated patients (hazard ratio 0.80; 95% CI: 0.62-1.03). Conclusions: These results suggest that further investigation is warranted of whether metformin may benefit the survival of patients with pancreatic cancer and concurrent type 2 diabetes.

Background: Aberrant expression of HOX gene expression has been observed in cancer. The purpose of this study was to investigate the alteration of HOXA5 and HOXA9 expression and their clinical significance in acute meloid leukemia (AML). Materials and Methods: The expression of HOXA5 and HOXA9 genes of bone marrow samples from 75 newly diagnosed AML patients and 22 healthy controls for comparison were examined by Real-time quantitative PCR (RQ-PCR) assay. Statistical analysis was conducted to evaluate HOXA5 and HOXA9 expression as possible biomarkers for AML. Results: The results showed that the complete remission rate (52.6%) of the patients who highly expressed HOXA5 and HOXA9 was significantly lower than that (88.9%) in patients who lowly express the genes (P=0.015). Spearmann correlation coefficients indicated that the expression levels for HOXA5 and HOXA9 genes were highly interrelated (r=0.657, P<0.001). Meanwhile, we detected significant correlations between HOXA9 expression and age in this limited set of patients (P=0.009). Conclusions: The results suggest a prognostic impact of increased expression of HOXA5 and HOXA9 in AML patients.

Background: For brachytherapy of cervical cancer, applicator shifts can not be avoided. The present investigation concerned Utrecht interstitial applicator shifts and their effects on organ movement and DVH parameters during 3D CT-based HDR brachytherapy of cervical cancer. Materials and Methods: After the applicator being implanted, CT imaging was achieved for oncologist contouring CTVhr, CTVir, and OAR, including bladder, rectum, sigmoid colon and small intestines. After the treatment, CT imaging was repeated to determine applicator shifts and OARs movements. Two CT images were matched by pelvic structures. In both imaging results, we defined the tandem by the tip and the base as the marker point, and evaluated applicator shift, including X, Y and Z. Based on the repeated CT imaging, oncologist contoured the target volume and OARs again. We combined the treatment plan with the repeated CT imaging and evaluated the change range for the doses of CTVhr D90, D2cc of OARs. Results: The average applicator shift was -0.16 mm to 0.10 mm for X, 1.49 mm to 2.14 mm for Y, and 1.9 mm to 2.3 mm for Z. The change of average physical doses and EQD2 values in Gy${\alpha}/{\beta}$ range for CTVhr D90 decreased by 2.55 % and 3.5 %, bladder D2cc decreased by 5.94 % and 8.77 %, rectum D2cc decreased by 2.94 % and 4 %, sigmoid colon D2cc decreased by 3.38 % and 3.72 %, and small intestines D2cc increased by 3.72 % and 10.94 %. Conclusions: Applicator shifts and DVH parameter changes induced the total dose inaccurately and could not be ignored. The doses of target volume and OARs varied inevitably.

Background: Colorectal cancer mortality has started to decrease in several developed countries in Asia. The current study aimed to present the long-term trends in colorectal cancer mortality in Korea using joinpoint analysis and age-period-cohort modeling. Materials and Methods: The number of colorectal cancer deaths and the population for each 5-year age group were obtained from Statistics Korea for the period 1984-2013 for adults 30 years and older. Joinpoint regression analysis was conducted to determine changes in trends in age-standardized mortality rates, and age-period-cohort analysis was performed to describe trends in colorectal cancer mortality using the intrinsic estimator method. Results: In men, the age-standardized mortality rate for colorectal cancer increased from 1984 to 2003, and the mortality rates stabilized thereafter, whereas the mortality rate of colorectal cancer in women has decreased since 2004. The age-specific mortality rate of colorectal cancer increased in both men and women over time, whereas decreases in the age-specific mortality rate in younger cohorts were observed. In the age-period-cohort analysis, old age and recent period were associated with higher mortality for both men and women. The birth cohort born after 1919 showed reduced colorectal cancer mortality in both men and women. Conclusions: Our study showed a recent decreasing trend in colorectal cancer mortality in women and a stable trend in men after 2003-2004. These changes in colorectal cancer mortality may be attributed to birth cohort effects.

Background: Several studies have examined the relationship between oral contraceptive pill (OCP) use, abortions and breast cancer, with mixed results. Hormonal changes associated with OCP use and abortion may increase risk of breast cancer over time, but there is a lack of studies studying this association in Saudi Arabian women. Materials and Methods: We thererfore conducted a case control study in 192 women (92 as cases and 100 as controls), aged 30 to 65, and collected information on variables including examples related to study objectives and those which may confound findings. The Chi square test was used to detect associations between various factors and risk of breast cancer. Results: We found no evidence of interaction between history of abortion or frequency of abortion and breast cancer risk (Chi square=0.422, p =0.420 and 1, p =0.169) respectively. Oral contraceptives did not confer risk for breast cancer overall (OR=0.276, 95%CI 0.092-0.829, p=0.524), while long term use of OCP was associated with increased risk of breast cancer (OR=0.297, 95%CI 0.158-0.557, p=0.001), with higher association for those who used 10 years or more of OCPs (OR=0.282, 95%CI 0.095-0.835, p=0.02). Age at first use of OCPs had no effect on breast cancer risk (p=0.452) or age at diagnosis (p=0.074). Conclusions: Prolonged use of OC (more than 10 years) may be associated with increased risk of breast cancer in Saudi women. Larger population based studies are needed to confirm this finding in this population.

Background: Variants of human papillomavirus (HPV) show more oncogenicity than do prototypes. The HPV16 Asian variant (HPV16As) plays a major role in cervical cancer of Asian populations. Some amino acid changes in the E6 protein of HPV16 variants affect E6 functions such as p53 interaction and host immune surveillance. This study aimed to investigate activities of HPV16As E6 protein on modulation of expression of miRNA-21 as well as interferon regulatory factors (IRFs) 1, 3, 7 and c-fos. Materials and Methods: Vectors expressing E6 protein of HPV16As (E6D25E) or HPV16 prototype (E6Pro) were constructed and transfected into C33A cells. HCK1T cells expressing E6D25E or E6Pro were established by transducing retrovirus-containing E6D25E or 16E6Pro. The E6AP-binding activity of E6 and proliferation of the transfected C33A cells were determined. MiR-21 and mRNA of interesting genes were detected in the transfected C33A cells and/or the HCK1T cells, with or without treatment by culture medium from HeLa cells (HeLa-CM). Results: E6D25E showed binding activity with E6AP similar to that of E6Pro. Interestingly, E6D25E showed a higher activity of miR-21 induction than did E6Pro in C33A cells expressing E6 protein. This result was similar to the HCK1T cells expressing E6 protein, with HeLa-CM treatment. The miR-21 up-regulation significantly corresponded to its target expression. Different levels of expression of IRFs were also observed in the HCK1T cells expressing E6 protein. Interestingly, when treated with HeLa-CM, IRFs 1, 3 and 7 as well as c-fos were significantly suppressed in the HCK1T cells expressing E6D25E, whereas those in the HCK1T cells expressing E6Pro were induced. A similar situation was seen for IFN-${\alpha}$ and IFN-${\beta}$. Conclusions: E6D25E of the HPV16As variant differed from the E6 prototype in its activities on epigenetic modulation and immune surveillance and this might be a key factor for the important role of this variant in cervical cancer progression.

Background: This analysis was conducted to evaluate the efficacy and safety of lenalidomide based regimen in treating patients with castration-resistant prostate cancer. Materials and Methods: Clinical studies evaluating the efficacy and safety of lenalidomide based regimens on response and safety for patients with castration-resistant prostate cancer were identified using a predefined search strategy. A pooled response rate (rate of PSA level decline of ${\geq}50%$) to treatment was calculated. Results: In lenalidomide based regimen, 3 clinical studies which including 98 patients with castration-resistant prostate cancer were considered eligible for inclusion. These lenalidomide based regimens included cisplatin, doxorubicin, or GM-CSF. Pooled analysis suggested that, in all patients, the pooled PSA level decline of ${\geq}50%$ was 13.3% (13/98) in lenalidomide based regimens. Fatigue, nausea and vomitting were the main side effects. No grade III or IV renal or liver toxicity were observed. No treatment related death occurred in patients with lenalidomide based regimens. Conclusions: This evidence based analysis suggests that lenalidomide based regimens are associated with mild response rate and acceptable toxicities for treating patients with castration-resistant prostate cancer.

Objectives: To explore the expression of aquaporin 1 ($AQP_1$) in bladder uroepithelium cell carcinoma (BUCC) and its relevance to recurrence. Materials and Methods: Tissue samples from 45 BUCC patients who underwent total cystectomy or transurethral resection of bladder tumor (TURBT) and from 40 patients with non-bladder cancers who underwent special detection or treatments were collected. The level of expression of $AQP_1$ in BUCC tissues and normal bladder tissues was assessed by immunohistochemistry so as to analyze the relevance to pathological patterns and time of recurrence in BUCC patients. Results: The expression levels of $AQP_1$ normal bladder tissues and BUCC tissues were $2.175{\pm}0.693$ and $3.689{\pm}0.701$, respectively, and the difference was significant (t=9.99, P<0.0001). Marked increase was noted with BUCC histological grade and pathological stage (P<0.01). Moreover, the expression of $AQP_1$ was evidently higher in cancerous tissues with lymph node metastasis than in those without (P<0.01). With short-term recurrence, the positive cell expression rate of $AQP_1$ was higher in primary tissues, which increased obviously after recurrence. Additionally, the recurrent time of BUCC was negatively associated with the positive cell expression rate of $AQP_1$ and the difference between the expression of $AQP_1$ before and after recurrence (r=-0.843, F=39.302, P=0.000; r=-0.829, F=35.191, P=0.000). Conclusions: $AQP_1$, which reflects the grade, stage, lymph node metastasis and recurrence of BUCC, has potential guiding significance in the diagnosis and treatment of bladder cancarcinoma.

Background: To investigate the effects of preemptive analgesia with parecoxib sodium on haemodynamics and plasma stress hormones in surgical patients with thyroid carcinoma. Materials and Methods: Fifty-seven patients with thyroid carcinoma who underwent thyroidectomy selectively in Laiwu Hospital Affiliated to Taishan Medical University and Binzhou People's Hospital were selected and randomly divided into three groups, 19 cases in each group. The control group was intravenously injected 0.9% sodium chloride injection before anesthesia induction; trial group I was intravenously injected with parecoxib sodium 20 min before anesthesia induction; based on trial group I, trial group II was injected with parecoxib sodium again 12 h after surgery. The levels of plasma norepinephrine (NE), cortisol (Cor) and blood glucose before, 12 and 24 h after surgery and changes of haemodynamics before surgery, at the end of surgery and 12, 24 and 48 h after surgery were compared in the three groups. Besides, visual analogue scale (VAS) scores were recorded 4, 8, 12 and 24 h after surgery. Results: 12 and 24 h after surgery, the levels of plasma NE and Cor in three groups rose dramatically (P<0.05 or (P<0.01); The levels of plasma NE and Cor in trial groups I and II were evidently lower than in control group (P<0.05 or P<0.01), and those in trial group II slightly lower than in trial group I. 12 h after surgery, the heart rates (HR) and systolic pressures (SBP) in trial groups I and II increased obviously by comparison to surgery before (P<0.05 or P<0.01), but gradually returned to the preoperative level. HR, SBP and diastolic pressures (DBP) in trial groups I and II at the end of surgery and 12 h after surgery were all lower than in the control group, and significant differences were present (P<0.05 or (P<0.01). At 4, 8, 12 and 24 h after surgery, VAS scores in trial groups I and II were markedly lower than in the control group (P<0.05 or (P<0.01), the scores in trial group II being the lowest. Conclusions: Combined application of parecoxib sodium for preemptive analgesia before anesthesia and after surgery can effectively reduce the levels of plasma stress hormones and improve analgesic effects in surgical patients with thyroid carcinoma, and without conspicuous impact on haemodynamics.

Background: Breast cancer is the most common type of cancer in Jordan. Current efforts are focused on annual campaigns aimed at increasing awareness about breast cancer and encouraging women to conduct mammogram screening. In the absence of regular systematic screening for breast cancer in Jordan, there is a need to evaluate current mammography screening uptake and its predictors, assess women's knowledge and attitudes towards breast cancer and screening mammograms and to identify barriers to this preventive service. Materials and Methods: This cross-sectional study was conducted in six governorates in Jordan through face-to-face interviews on a random sample of women aged 40 to 69 years. Results: A total of 507 participants with mean age of $46.8{\pm}7.8$ years were interviewed. There was low participation rate in early detection of breast cancer practices. Breast self-examination, doctor examination and periodic mammography screening were reported by 34.9%, 16.8% and 8.6% of study participants, respectively. Additionally 3.8% underwent breast cancer screening at least once but not periodically, while 87.6% had never undergone mammography screening. Reported reasons for conducting the screening were: perceived benefit (50%); family history of breast cancer (23.1%); perceived severity (21.2%); and advice from friend or family member (5.8%). City residents have shown higher probability of undergoing mammogram than those who live in towns or villages. Results revealed negative perceptions and limited knowledge of study participants on breast cancer and breast cancer screening. The most commonly reported barriers for women who never underwent screening were: fear of results (63.8%); no support from surrounding environment (59.7); cost of the test (53.4%); and religious belief, i.e. Qadaa Wa Qadar (51.1%). Conclusions: In the absence of regular systematic screening for breast cancer in Jordan, the uptake of this preventive service is very low. It is essential for the country of Jordan to work on applying regular systematic mammography screening for breast cancer. Additionally, there is a need for improvement in the current health promotion programmes targeting breast cancer screening. Other areas that could be targeted in future initiatives in this field include access to screening in rural areas and removal of current barriers.

Background: Colorectal cancer (CRC) is the third most common cancer in Iranian women and fifth in men. The aims of this study were to investigate the relation of dietary factors and public health indicators to its development. Materials and Methods: The required information (2001-2006) about risk factors was obtained from the Non-Communicable Disease Surveillance Centre (NCDSC) of Iran. Risk factor data (RFD) from 89,404 individuals (15-64 years old) were gathered by questionnaire and laboratory examinations through a cross sectional study in all provinces by systematic clustering sampling method. CRC incidence segregated by age and gender was obtained from Cancer Registry Ministry of Health (CRMH) of Iran. First, correlation coefficients were used for data analysis and then multiple regression analysis was performed to control for confounding factors. Results: Colorectal cancer incidence showed a positive relationship with diabetes mellitus, hypertension, lacking or low physical activity, high education, high intake of dairy products, and non-consumption of vegetables and fruits. Conclusions: We concluded that many dietary factors and public health indicators have positive relationships with CRC and might therefore be targets of preliminary prevention. However, since this is an ecological study limited by potential ecological fallacy the results must be interpreted with caution.

Background: Systemic inflammatory response was shown to play an important role in development and progression of many cancer types and different inflammation-based indices were used for determining prognosis. We aimed to investigate the prognostic effects of neutrophil to lymphocyte ratio (NLR) and prognostic nutritional index (PNI) in patients with non-small cell lung cancer (NSCLC). Materials and Methods: NSCLC patients diagnosed in our institution were retrospectively reviewed. Demographic and clinicopathologic characteristics were recorded. NLR and PNI was calculated before the application of any treatment. Results: A total of 138 patients were included in the study. Patients were divided into two groups according to NLR (<3.24 or ${\geq}3.24$) and PNI (<49.5 or ${\geq}49.5$). While median overall survival was 37.0 (95% CI 17.5-56.5) months in the group with low NLR, it was calculated as 10.0 (95%CI 5.0-15.0) months in the group with high NLR (p<0.0001). While median overall survival was 7.0 (95%CI 3.5-10.5) months in the group with low PNI, it was calculated as 33.0 (95% CI 15.5-50.4) months in the group with high PNI (p<0.0001). Stage, NLR and PNI levels were evaluated as independent risk factors for overall survival for all patients in multivariate analysis (p<0.0001, p=0.04 and p<0.001, respectively). Conclusions: NLR (${\geq}3.24$) and PNI (<49.5) at diagnosis is an independent marker of poor outcome in patients with NSCLC. NLR and PNI is an easily measured, reproducible prognostic tests that could be considered in NSCLC patients.

Objecive: To investigate the clinical safety and efficacy of CT-guided $^{125}iodine$ (125I) seed implantation combined with percutaneous intra-tumor injection of chemotherapy emulsion of lobaplatin and lipiodol in treating patients with advanced lung cancer. Materials and Methods: Patients with advanced lung cancer and treated with spiral CT-guided $^{125}I$ seed implantation combined with percutaneous intra-tumor injection of chemotherapy emulsion of lobaplatin and lipiodol were recruited. Results: Of the 36 patients, there were 40 nidi in total. The contrast-enhanced CT evaluation was conducted 60 d after treatment. Response evaluation suggested that 4 patients achieved complete remission (CR), 24 partial remission (PR), 4 stable disease (SD) and 4 progression disease (PD), with a total response rate of 77.8% (28/36). Conclusions: CT-guided $^{125}I$ seed implantation combined with percutaneous intra-tumor injection of chemotherapy emulsion of lobaplatin and lipiodol are safe and effective in treating patients with advanced lung cancer.

Objective: To explore the expression of RECK and relevant matrix metalloproteinases (MMPs) in hepatoblastoma (HB) and neuroblastoma (NB) and their clinical significance in the tumor metastasis. Materials and Methods: Forty-five wax-stone samples of HB and 43 wax-stone samples of NB removed by surgical resection and confirmed by pathology in Linyi Yishui Central Hospital were selected. According to presence and absence of metastasis, both NB and HB samples were divided into metastatic group and non-metastatic group, namely NB metastatic group (n=28), NB non-metastatic group (n=15), HB metastatic group (n=15) and HB non-metastatic group (n=30). The expression of RECK, membrane type-1 matrix metalloproteinase (MT1-MMP) in HB tissue and RECK, MMP-14 in NB tissue was detected using immunohistochemical method, and the correlation between RECK and MT1-MMP, MMP-14 was analyzed. Results: The metastatic rate of NB was dramatically higher than that of HB, with statistical significance (P=0.003). The positive rate of RECK expression in NB group (30.2%) was slightly lower than in HB group (40.0%), but no significant difference was presented (P=0.338). The positive rate of MMPs expression in NB metastatic group was evidently higher than in HB metastatic group (P=0.024). The results of Spearman correlation analysis revealed that the expression of RECK in HB and NB tissues had a significantly-negative correlation with MT1-MMP and MMP-14, respectively (r=-0.499, P=0.012; r=-0.636, P=0.000). Conclusions: In HB and NB tissues, RECK is expressed lowly, while relevant MMPs highly, and RECK inhibits the tumor invasion and metastasis through negative regulation of relevant MMPs.

Objective: To explore the clinical application of recombinant human endostatin (Endostar) in the treatment of patients with non-small cell lung cancer (NSCLC) in Chinese mainland. Materials and Methods: A total of 75 patients diagnosed as NSCLC were randomly divided into control group (37 cases) and treatment group (38 cases). Control group was treated with postoperative complementary chemotherapy containing two-agent platinum protocol on postoperative d21, 3 weeks as a cycle, for totally 4~6 cycles. On this basis, treatment group was added with Endostar $7.5mg/m^2$ on postoperative d8~9, 3~4 h/time, qd, 14 weeks as a cycle, for totally 4 cycles. The interval between every two cycles was 7 d. The 5-year progression-free survival (PFS), 5-year survival time and complications in both groups were observed. Results: Compared with control group, the average PFS increased evidently in treatment group by 9.8 months (41.6 months vs. 31.8 months), and there was significant difference (P<0.05). And the median PFS was 42.5 months in treatment group, obviously longer than that in control group (33.7 months) by 8.8 months (P<0.05). Additionally, the 5-year overall survival rate (OS), average survival time and median survival time (MST) were 47.4%, 50.1 months and 59.3 months in treatment group, significantly higher than the 29.7%, 42.1 months and 43.5 months in control group (P<0.05). Only 1 patient showed poor healing of surgical wound in treatment group, but no surgery-associated complication was found in control group. Moreover, the postoperative complementary therapy-connected complication rates were 63.2% (24/38) and 59.5% (22/37) in treatment group and control group respectively, but there was no significant difference (P>0.05). Conclusions: The application of Endostar combined with sensitive platinum-contained chemotherapeutic agents in the postoperative complementary chemotherapy can be widely used in clinic because it can significantly prolong the long-term survival time of patients with NSCLC.

Background: Breast cancer is the most frequently occurring cancer in women and the most common cause of cancer death worldwide. Materials and Methods: A cross-sectional study was carried out among 792 female undergraduate students in public universities in Klang Valley, Malaysia, from January to April 2011. Data were collected using a validated questionnaire developed for this study. Results: The mean age of respondents was $21.7{\pm}1.2$ years. Most of them were single (96.8%), Malay (91.9%) and 150 (19.6%) claimed they had practiced BSE. There was a significant differences between performers and non-performers correlated to age, marital status, check breast by doctor, and being trained about BSE. Performers had lower mean scores for perceived barriers and susceptibility and higher mean score for confidence. Stepwise logistic regression analysis yielded four significant predictor variables. Conclusions: Overall our findings indicate that the practice of BSE while perceived as being important is not frequently practiced among female in Malaysia. Targeted education should be implemented to improve early detection of breast cancer.

Background: Gastrointestinal tract cancers are among the most common cancers in Iran and comprise approximately 38% of all the reported cases of cancer. This study aimed to describe the epidemiology and to investigate spatial clustering of common cancers of the gastrointestinal tract across the counties of Iran using full Bayesian smoothing and Moran I Index statistics. Materials and Methods: The data of the national registry cancer were used in this study. Besides, indirect standardized rates were calculated for 371 counties of Iranand smoothed using Winbug 1.4 software with a full Bayesian method. Global Moran I and local Moran I were also used to investigate clustering. Results: According to the results, 75,644 new cases of cancer were nationally registered in Iran among which 18,019 cases (23.8%) were esophagus, gastric, colorectal, and liver cancers. The results of Global Moran's I test were 0.60 (P=0.001), 0.47 (P=0.001), 0.29 (P=0.001), and 0.40 (P=0.001) for esophagus, gastric, colorectal, and liver cancers, respectively. This shows clustering of the four studied cancers in Iran at the national level. Conclusions: High level clustering of the cases was seen in northern, northwestern, western, and northeastern areas for esophagus, gastric, and colorectal cancers. Considering liver cancer, high clustering was observed in some counties in central, northeastern, and southern areas.

Background: Breast cancer is one of the most feared diseases among women and it could induce the development of psychological disorders like anxiety and depression. An assessment was here performed of the status and to determine contributory factors. Materials and Methods: A cross-sectional study was conducted among breast cancer patients at University Kebangsaan Malaysia Medical Center (UKMMC), Kuala Lumpur. A total of 205 patients who were diagnosed between 2007 until 2010 were interviewed using the questionnaires of Hospital Anxiety and Depression (HADS). The associated factors investigated concerned socio-demographics, socio economic background and the cancer status. Descriptive analysis, chi-squared tests and logistic regression were used for the statistical test analysis. Results: The prevalence of anxiety was 31.7% (n=65) and of depression was 22.0% (n=45) among the breast cancer patients. Age group (p= 0.032), monthly income (p=0.015) and number of visits per month (p=0.007) were significantly associated with anxiety. For depression, marital status (p=0.012), accompanying person (p=0.041), financial support (p-0.007) and felt burden (p=0.038) were significantly associated. In binary logistic regression, those in the younger age group were low monthly income were 2 times more likely to be associated with anxiety. Having less financial support and being single were 3 and 4 times more likely to be associated with depression. Conclusions: In management of breast cancer patients, more care or support should be given to the young and low socio economic status as they are at high risk of anxiety and depression.

Objective: To explore the clinical efficacy and toxic and side effects of recombinant human endostatin (rhendostatin/endostar) combined with chemotherapy in the treatment of advanced gastric cancer. Materials and Methods: A total of 70 patients with advanced gastrointestinal adenocarcioma confirmed by histopathology and/or cytological examination were divided into group A (37 patients) and group B (33 patients). Patients in group A were given intravenous drip of 15 mg endostar added into 500 mL normal saline, once every other day until the cessation of chemotherapy or patients' maximal tolerance to chemotherapy. Patients in group B received chemotherapy alone. Two groups selected the same chemotherapy regimens. FOLFIRI scheme: 90-min intravenous drip of $180mg/m^2$ irinotecan, intravenous drip of $200mg/m^2$ calcium folinate (CF) and $400mg/m^2$ 5-fluorouracil (5-Fu) on d1, and continuous intravenous pumping of 2 $400mg/m^2$ 5-Fu for 46 h. FOLFOX4 scheme: intravenous injection of $85mg/m^2$ oxaliplatin (L-OHP), $200mg/m^2$ calcium folinate (CF) and $400mg/m^2$ 5-FU on d1 for 2 h, and then continuous intravenous pumping of 2 $400mg/m^2$ 5-Fu for 46 h. XELOX scheme: oral administration of 1 $500mg/m^2$ xeloda (or tegafur 50~60 mg) in twice during d1~14 and intravenous drip of $135mg/m^2$ L-OHP on d1 for 2 h. The modified FOLFOX scheme: intravenous injection of $135mg/m^2$ L-OHP on d1 for 2 h, $200mg/m^2$ CF and 1.0 g tegafur during d1~5. Whereas, control Group B received chemotherapy regimens which were same as Group A, but no addition of endostar. Before chemotherapy, patients were given intravenous injection of 8 mg ondansetron, intramuscular injection of 10 mg metoclopramide and 20 mg diphenhydramine for prevention of vomiting, protection of liver and stomach as well as symptomatic supportive treatment. One cycle was 21 d, 4~6 cycles in total. The efficacy was evaluated every 2 cycles. Results: 32 patients in Group A could be evaluated, and the response rate (RR) and disease control rate (DCR) were 59.38% and 78.13%, respectively. 31 patients in Groups could be evaluated, and the RR and DCR were 32.26% and 54.84%, respectively. The differences between 2 groups were significant. The toxic effects include myelosuppression, gastrointestinal reaction, fatigue, cardiotoxicity and peripheral neurotoxicity. Conclusions: Preliminary observations show that endostar (once every other day) combined with chemotherapy is effective in the treatment of advanced gastrointestinal cancer, with low toxic effects, good tolerance, deserving further study.

Background: To verify whether serum tumor abnormal protein (TAP) would correlate with the responsiveness of palliative chemotherapy in patients with advanced gastric cancer, and the variation of conventional serum tumor markers e.g., carcinoembryonic antigen (CEA), antigen 125 (CA125),carbohydrate antigen19-9 (CA19-9) of adjuvant chemotherapy in patients with early gastric cancer. Materials and Methods: Patients with histologically confirmed gastric cancer and treated with chemotherapy were enrolled into this study. TAP values of these patients were determined by detecting abnormal sugar chain glycoprotein in serum, combined with the area of agglomerated particles. For patients with advanced gastric cancer, responsiveness of palliative chemotherapy was compared with variation of TAP and the relation between variation of TAP and tumor markers in patients with early gastric cancer was analyzed. Results: Totally 82 gastric cancer patients were enrolled into this study. The value of TAP is more closely related to responsiveness of palliative chemotherapy for patients with advanced gastric cancer. The correlation between TAP and responsiveness to palliative chemotherapy is stronger than the correlation between several conventional serum tumor markers (CEA, CA125 and CA199). The variation of TAP was also positively correlated with the trend of CA125 in adjuvant chemotherapy. Conclusions: TAP is sensitive in monitoring the responsiveness to palliative chemotherapy in patients with advanced gastric cancer. But this result should be confirmed by randomized clinical trials for patients with gastric cancer.

Objective: To investigate the effect of coenzyme complex on decreasing cardiotoxicity in elderly patients with gastrointestinal cancer who were treated by chemotherapy. Methods: From September 2011 to February 2015, we recruited 54 elderly (with more than 70 years of age) patients with gastrointestinal cancer, with advanced disease. Then treated with chemotherapy combined with or without coenzyme complex. After two cycles of treatment, the effect of coenzyme complex on decreasing cardiotoxicity were evaluated. Results: Chemotherapy was combined with coenzyme complex in 32 patients (22man, 10 woman; median age: 74 years, range: 70-87 years) without coenzyme complex in 22 patients (15man, 7 woman; median age: 73 years, range: 70-80 years) with gastrointestinal cancer. Cardiac event was significantly lower in patients treated with chemotherapy combined with coenzyme complex (p<0.01). Conclusions: Coenzyme Complex decreased cardiotoxicity when combined with chemotherapy in treating elderly patients with gastrointestinal cancer.

The purpose of this study is to assess the effect of consanguinity on breast cancer incidence in Tunisia. We conducted a case-control study to evaluate the involvement of heterozygote and homozygote haplotypes of BRCA1 gene SNPs according to consanguinity among 40 cases of familial breast cancer, 46 cases with sporadic breast cancer and 34 healthy controls. We showed significant difference in consanguinity rate between breast cancer patients versus healthy controls P=0.001. Distribution of homozygous BRCA1 haplotypes among healthy women versus breast cancer patients was significantly different; p=0.02. Parental consanguinity seems to protect against breast cancer in the Tunisian population.

Cigarette smoke contains oxidants and free radicals which are carcinogens that can induce mutations in humans. Single nucleotide polymorphisms (SNPs) are the most frequent genetic alterations found in the human genome. In the present study, we have examined the ability of the murine double minute 2 (Mdm2) (rs769412) A>G polymorphism in cigarette smokers to predict risk of cancers. Our results showed that of smokers, 87% were found with AA genotype, 10% with heterozygous AG genotype, and 3% with GG genotype. The heterozygous AG genotype was observed in a lower percentage of smokers (10%) as compared to non-smokers (18%), whereas, homozygous AA genotype was observed in lower percentage of non-smokers (81%) as compared to the smokers (87%). The results from present study support the association with an allele and AG genotype in non-smokers. However, further studies are required to establish the role of Mdm2 (rs769412) C>T in cigarettes smokers and diseases.

Background: To evaluate pathological features of head and neck squamous cell carcinoma (HNSCC) and to compare these pathological features in patients younger and older than 40 years. Materials and Methods: All resection specimens of HNSCC between 2010 and 2013 evaluated. Tumor characteristics - grade, location (site) cervical node status, alongwith presence or absence of extranodal extension, lymphovascular invasion, gender and age - were extracted from surgical pathology reports. Results: Among these n=19 patients (21.8%) were 40 years or younger and n=68 patients (78.2%) were above 40 years of age. The mean age was 34 (20-40 years) in the younger group and 56 (42-86) in the older group. The most common location of HNSCC in both groups was the oral cavity. The analysis of histopathological features including grade of tumor, tumor size, extranodal extension and comparison between two groups do not show any significant difference. Conclusions: There are no specific pathological characteristics of HNSCC in young patients. An interesting observation is that exposure to expected risk factors is similar in both groups, in younger patients they have less time to act and yet tumors are the same in terms of tumor size, lymph node status and lymphovascular invasion. Therefore further research is recommended to look for potentiating factors.

Background: Epidermal growth factor-like domain multiple 7 (EGFL7), a secreted protein specifically expressed by endothelial cells during embryogenesis, recently was identified as a critical gene in tumor metastasis. Epithelial-mesenchymal transition (EMT) was found to be closely related with tumor progression. Accordingly, it is important to investigate the migration and EMT change after knock-down of EGFL7 gene expression in human pancreatic cancer cells. Materials and Methods: EGFL7 expression was firstly testified in 4 pancreatic cancer cell lines by real-time polymerase chain reaction (Real-time PCR) and western blot, and the highest expression of EGFL7 was found in PANC-1 cell line. Then, PANC-1 cells transfected with small interference RNA (siRNA) of EGFL7 using plasmid vector were named si-PANC-1, while transfected with negative control plasmid vector were called NC-PANC-1. Transwell assay was used to analyze the migration of PANC-1 cells. Real-time PCR and western blotting were used to detect the expression change of EGFL7 gene, EMT markers like E-Cadherin, N-Cadherin, Vimentin, Fibronectin and transcription factors like snail, slug in PANC-1, NCPANC-1, and si-PANC-1 cells, respectively. Results: After successful plasmid transfection, EGFL7 gene were dramatically knock-down by RNA interference in si-PANC-1 group. Meanwhile, migration ability decreased significantly, compared with PANC-1 and NC-PANC-1 group. Meanwhile, the expression of epithelial phenotype marker E-Cadherin increased and that of mesenchymal phenotype markers N-Cadherin, Vimentin, Fibronectin dramatically decreased in si-PANC-1 group, indicating a reversion of EMT. Also, transcription factors snail and slug decreased significantly after RNA interference. Conclusions: Current study suggested that highly-expressed EGFL7 promotes migration of PANC-1 cells and acts through transcription factors snail and slug to induce EMT, and further study is needed to confirm this issue.

Background: Retinoblastoma protein-interacting zinc finger gene 1(RIZ1) functions as a tumor suppressor. Hypermethylation-mediated RIZ1 silencing has been reported in several cancers, but not in renal cell carcinoma (RCC) yet. Materials and Methods: We examined the RIZ1 expression and methylation in a panel of RCC cell lines and 50 primary tumors using semiquantitative/quantitative polymerase chain reaction (PCR), methylation specific PCR, and bisulfite sequencing genomic. We also explored the relationship between methylation status of RIZ1 and clinicopathological features in RCC patients. Results: RIZ1 expression was down-regulated or lost in OS-RC-2, 769-P, Caki-1, 786-O and A498 RCC cell lines. Restored expression of RIZ1 was detected after addition of 5-aza-2'-deoxycytidine with/without trichostatin A, suggesting that DNA methylation directly mediates its silencing. The RIZ1 expression was significantly reduced in RCCs compared to adjacent non-malignant renal samples (P<0.001). Aberrant methylation was detected in 15 of 50 (30%) RCCs and in 2 of 28 (7%) adjacent non-malignant renal samples (P=0.02). No statistically significant correlation between methylated and unmethylated cases with regard to age, gender, pathological stage and grade was observed. Conclusions: RIZ1 expression is down-regulated in human RCC, and this down-regulation is associated with methylation. RIZ1 methylation may play a role in renal carcinogenesis.

The chemokine receptor 4 (CXCR4) has been widely used in diagnosis and prognosis of colorectal cancer (CRC). However, there is no current consensus on the impact of CXCR4 on CRC patients. The purpose of this study was to evaluate the prognostic and clinicopathological importance of CXCR4 in CRC patients. Databases, such as PubMed, Cochrane library, CBM and EMBASE updated to 2014 were searched to include eligible articles. We analysed correlations between CXCR4 expression and clinicopathological features and overall survival (OS). A total of 1, 055 CRC patients from twelve studies were included in the study. The pooled odds ratios (ORs) which indicated CXCR4 expression was likely to be associated with TNM stage (OR=0.43, CI=0.34-0.55, P<0.00001), lymph node status (OR=2.23, CI=1.23-4.05, P=0.008) and vascular invasion (OR=2.21, CI=1.11-4.39, P=0.02). Poor overall survival of CRC cancer was found to be significantly related to CXCR4 overexpression (hazard ratio (HR) 1.36 CI=1.17-1.59, P<0.0001), whereas combined ORs revealed that CXCR4 expression had no correlation with gender or differentiation. Based on the published studies, CXCR4 overexpression in patients w ith CRC indicates poor survival outcome and clinicopathological factors.

Background: Men and women who smoke tend to show less compliance to screening guidelines than non-smokers. However, a recent study in Korea showed that self-reported female smokers constituted less than half of cotinine-verified smokers. Therefore, the aim of this study was to identify hidden smokers using cotinine-verified method and examine cancer screening behavior according to biochemically verified smoking status. Materials and Methods: Among 5,584 women aged 30 years and older who participated in the Fourth and Fifth Korea National Health and Nutrition Examination Survey (KNHANES), 372 (6.66%) hidden smokers were identified based on interview responses and verified by urinary cotinine levels. We compared cancer-screening behavior (cervical, breast, stomach, and colon cancer) of female hidden smokers to that of non-smokers and selfreported smokers by cross-sectional analysis. Results: Hidden female smokers had significantly lower adherence to breast cancer screening compared to non-smokers (aOR (adjusted odds ratio) [95% CI] = 0.71 [0.51-0.98]). Adherence to stomach cancer (aOR [95% CI] = 0.75 [0.54-1.03]) and cervical cancer (aOR [95% CI] = 0.85 [0.66-1.10]) screening was also lower among hidden female smokers compared to non-smokers. Self-reported (current) smokers showed lowest adherence to cervical cancer (aOR: 0.64, 95% CI0.47-0.87), breast cancer (0.47 [0.32-0.68]), stomach cancer (0.66[0.46-0.95]), and colon cancer (0.62 [0.38-1.01]) screening compared to non-smokers, followed by female hidden smokers, then non-smokers. These lower adherence rates of current smokers were attenuated after we incorporated hidden smokers into the current smoker group. Conclusions: Cancer screening adherence of female hidden smokers was lower than cotinine-verified non-smokers but higher than current smokers. Considering the risk of smoking-related cancer among women, identifying hidden smokers is important to encourage appropriate cancer screening.

The purpose of the research was to determine the effect of home care service on the quality of life in patients with gynecological cancer. This randomized case control study was carried out in a womans hospital between September 2011 and February 2012. Women undergoing gynecological cancer treatment were separated into intervention and control groups, of 35 patients each. The intervention group was provided with nursing care service through hospital and home visits ($1^{st}$, $12^{th}$ weeks) within the framework of a specifically developed nursing care plan. The control group was monitored without any intervention through the hospital routine protocols ($1^{st}$, $12^{th}$ weeks). Data were collected using An Interview Form, Home Visit Monitoring Form and Quality of Life Scale/Cancer Survivors. Effects of home care service on the quality of life in gynecological cancer patients were investigated using chi-square tests, McNemar's test, independent t-test and ANOVA. This study found that the intervention group receiving home care service had a moderately high quality of life (average mean: $6.01{\pm}0.64$), while the control group had comparatively lower quality (average mean: $4.35{\pm}0.79$) within the 12 week post-discharge period (p<0.05). This study found home care services to be efficient in improving the quality of life in patients with gynecological cancer.

IDH1/2 mutations which result in alternation in DNA methylation pattern are one of the most common methylation associated mutations in Acute myeloid leukaemia. IDH1/2 mutations frequently associated with higher platelet level, normal cytogentics and NPM1 mutations. Here we analyzed IDH1/2 mutations in 200 newly diagnosed unselected Indian adult AML patients and investigated their correlation with clinical, cytogenetic parameters along with cooperating NPM1 mutation. We detected 5.5% and 4% mutations in IDH1/2 genes, respectively. Except IDH2 c.515_516GG>AA mutation, all the other identified mutations were reported mutations. Similar to reported c.515G>A mutation, the novel c.515_516GG>AA mutation replaces $172^{nd}$ arginine to lysine in the active site of the enzyme. Even though there was a preponderance of IDH1/2 mutations in NK-AML, cytogenetically abnormal patients also harboured IDH1/2 mutations. IDH1 mutations showed significant higher platelet count and NPM1 mutations. IDH2 mutated patients displayed infrequent NPM1 mutations and lower WBC count. All the NPM1 mutations in the IDH1/2 mutated cases showed type A mutation. The present data suggest that IDH1/2 mutations are associated with normal cytogenetics and type A NPM1 mutations in adult Indian AML patients.

Background: Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies worldwide. Transarterial chemoembolisation (TACE) is the standardized therapy for intermediate stage HCC. However, the prognosis for HCC patients treated by TACE greatly varies. Thus, there is a critical need for finding biomarkers to predict the prognosis of HCC patients. The amino acid transporter-2 (ASCT2) is involved in tumorigenesis and progression of many malignancies. This study aimed to evaluate the predictive role of two single nuclear polymorphisms (SNPs, rs3826793 and rs2070246) in the ASCT2 gene in HCC patients treated by TACE. Materials and Methods: Two functional SNPs (rs3826793 and rs2070246) in the ASCT2 gene were selected and genotyped using the Sequenom iPLEX genotyping system in a cohort of 448 unresectable Chinese HCC patients treated by TACE. Univariate and multivariate Cox proportional hazards models and Kaplan-Meier curves were used for the prognosis analyses. Results: There was no significant association between two SNPs (rs3826793 and rs2070246) in the ASCT2 gene and overall survival of TACE treated HCC patients. However, we demonstrated that patients with early stage HCC carrying T genotype in rs2070246 showed better OS than those carrying CC genotype (P=0.023). Conclusions: We demonstrated that patients with early stage HCC carrying T genotype in rs2070246 showed better OS than those carrying CC genotype.

Background: Full-field digital mammography (FFDM) with dense breasts has a high rate of missed diagnosis, and digital breast tomosynthesis (DBT) could reduce organization overlapping and provide more reliable images for BI-RADS classification. This study aims to explore application of COMBO (FFDM+DBT) for effect and significance of BI-RADS classification of breast cancer. Materials and Methods: In this study, we selected 832 patients who had been treated from May 2013 to November 2013. Classify FFDM and COMBO examination according to BI-RADS separately and compare the differences for glands in the image of the same patient in judgment, mass characteristics display and indirect signs. Employ Paired Wilcoxon rank sum test was used in 79 breast cancer patients to find differences between two examine methods. Results: The results indicated that COMBO pattern is able to observe more details in distribution of glands when estimating content. Paired Wilcoxon rank sum test showed that overall classification level of COMBO is higher significantly compared to FFDM to BI-RADS diagnosis and classification of breast (P<0.05). The area under FFDM ROC curve is 0.805, while that is 0.941 in COMBO pattern. COMBO shows relation of mass with the surrounding tissues, the calcification in the mass, and multiple foci clearly in breast cancer tissues. The optimal sensitivity of cut-off value in COMBO pattern is 82.9%, which is higher than that in FFDM (60%). They share the same specificity which is both 93.2%. Conclusions: Digital Breast Tomosynthesis (DBT) could be used for the BI-RADS classification in breast cancer in clinical.

Background: Colorectal cancer is the second most common cause of cancer death with half a million deaths per year. Incidence and mortality rates have demonstrated notable changes in Asian and African countries during the last few decades. In this study, we first aimed to determine the trend of colorectal cancer mortality rate in each Institute for Health Metrics and Evaluation (IHME) region, and then re-classify them to find more homogenous classes. Materials and Methods: Our study population consisted of 52 countries of Asia and North Africa in six IHME pre-defined regions for both genders and age-standardized groups from 1990 to 2010.We first applied simple growth models for pre-defined IHME regions to estimate the intercepts and slopes of mortality rate trends. Then, we clustered the 52 described countries using the latent growth mixture modeling approach for classifying them based on their colorectal mortality rates over time. Results: Statistical analysis revealed that males and people in high income Asia pacific and East Asia countries were at greater risk of death from colon and rectum cancer. In addition, South Asia region had the lowest rates of mortality due to this cancer. Simple growth modeling showed that majority of IHME regions had decreasing trend in mortality rate of colorectal cancer. However, re-classification these countries based on their mortality trend using the latent growth mixture model resulted in more homogeneous classes according to colorectal mortality trend. Conclusions: In general, our statistical analyses showed that most Asian and North African countries had upward trend in their colorectal cancer mortality. We therefore urge the health policy makers in these countries to evaluate the causes of growing mortality and study the interventional programs of successful countries in managing the consequences of this cancer.

Background: Carcinoma of the esophagus is associated with significant morbidity and mortality. The most common subtype is squamous cell carcinoma (SCC). In the past three decades, the incidence of SCC has been reported to be decreasing whereas esophageal adenocarcinoma (AC) is increasing. This study assessed the trend of esophageal cancer in Brunei Darussalam over a three decades period. Materials and Methods: The National Cancer registry was searched for esophageal cancers from 1986 to 2012. Data on age, gender, racial groups (Malays, Chinese, Indigenous and foreign nationals) and histology type were collected. The rate (ASR) and Age Specific Incidence rate (ASIR) were calculated. Results: The predominant tumor type was SCC which accounted for 89% of all esophageal cancer. The gender ratio was 2.25: 1 (male: female) and the mean age at diagnosis was $66.9{\pm}12.9$ years, significantly younger for esophageal AC ($57.2{\pm}16.0$) compared to SCC ($68.1{\pm}12.0$, p<0.05), and among the foreign nationals (p<0.05 for trend). The proportions of SCC among all esophageal cancers in the various racial groups were: Malays (87.8%), Chinese (100%), Indigenous (100%) and foreign nationals (20%). None of the Chinese and Indigenous groups were diagnosed with esophageal AC. The overall ASR for esophageal cancer was 2.1/100,000; 2.0/100,000 for SCC with a declining trend and 0.17/100,000 for esophageal AC, without any trend observed. Among the two major racial groups; the Chinese has higher ASR (3.42/100,000) compared to the Malays (ASR 0.95/100,000). Conclusions: SCC is the predominant tumor type of esophageal cancer in Brunei Darussalam and more common among the Chinese. There was a declining trend in the incidence of SCC but not for esophageal AC.

Background: For HER2 positive metastatic breast cancer (MBC), continuing anti-HER2 therapy beyond progression is associated with improved outcome. However retreatment with trastuzumab after lapatinib progression is controversial. We retrospectively analyzed the efficacy of trastuzumab-based chemotherapy in HER2+ metastatic breast cancer patients whose disease progressed after lapatinib. Materials and Methods: Between October 2010 and May 2013, 54 patients whose disease progressed after lapatinib were retreated with trastuzumab-based chemotherapy. Efficacy and toxicity results were evaluated retrospectively. Results: The median age of patients was 46 (range 27-67). Fourteen patients (26%) had metastases at the time of diagnosis. All of the patients had received trastuzumab in an adjuvant or metastatic setting, while 16 (30%) had received two lines of trastuzumab. All patients had received lapatinib plus capecitabine. The median chemotherapy line for the metastatic setting was 2 (range 1-7). Cranial metastases were identified in 27 (50%) patients. 53 patients received trastuzumab-based chemotherapy following lapatinib progression while one patient received trastuzumab monotherapy. Combination chemotherapy consisted of navelbin (n=33), taxane (n=10), gemcitabine (n=2), platinum (n=2) and platinum with taxane (n=6). The median treatment cycle was 5 (range 1-44). Among 49 patients assessed for response 2 (4%) showed CR, 12 (25%) PR, 11 (22%) SD and 24 (49%) disease progression. Asymptomatic cardiotoxicity was reported in 2 (4%) of the patients. At a median follow-up of 9 months (1-39), median progression-free survival was 5 months (95% CI 4.1-5.9) and median overall survival was 10 months (95% CI 6.9-13.0). PFS and OS were not affected by the absence/presence of cranial metastases. Conclusions: Retreatment with trastuzumab-based therapy after lapatinib progression showed efficacy in heavily treated MBC patients.

Background: To analyze multi-source data including publications and patents, and try to draw the whole landscape of the research and development community in the field of gene therapy for breast cancer. Materials and Methods: Publications and patents were collected from the Web of science and databases of the five major patent offices of the world, respectively. Bibliometric methodologies and technology are used to investigate publications/patents, their contents and relationships. Results: A total of 2,043 items published and 947 patents from 1994 to 2013 including "gene therapy for breast cancer" were retrieved. The top five countries in global publication share were USA, China, Germany, Japan and England. On the other hand, USA, Australia, England, South Korea and Japan were the main producers of patents. The universities and enterprises of USA had the highest amount of publication and patents. Adenovirus- and retrovirus-based gene therapies and small interfering RNA (siRNA) interference therapies were the main topics both in publications and patents. Conclusions: The above results show that global research in the field of gene therapy for breast cancer is increasing and the main participants in this field are USA and Canada in North America, China, Japan and South Korea in Asia, and England, Germany, and Italy in Europe. Also, this article demonstrates the usefulness of bibliometrics to address key evaluation questions and define future areas of research.

The zinc finger transcription factor EGR 1 has a role in controlling synaptic plasticity, wound repair, female reproductive capacity, inflammation, growth control, apoptosis and tumor progression. Recent studies mainly focused on its role in growth control and apoptosis, however, little is known about its role in epithelial-mesenchymal transition (EMT). Here, we aim to explore whether EGR 1 is involved in TGF-${\beta}1$-induced EMT in non-smallcell lung cancer cells. Transforming growth factor (TGF)-${\beta}1$ was utilized to induce EMT in this study. Western blotting, RT-PCR, and transwell chambers were used to identify phenotype changes. Western blotting was also used to observe changes of the expression of EGR 1. The lentivirus-mediated EGR 1 vector was used to increase EGR 1 expression. We investigated the change of migration to evaluate the effect of EGR 1 on non-small-cell lung cancer cells migration by transwell chambers. After stimulating with TGF-${\beta}1$, almost all A549 cells and Luca 1 cells (Non-small-cell lung cancer primary cells) changed to mesenchymal phenotype and acquired more migration capabilities. These cells also had lower EGR 1 protein expression. Overexpression of EGR 1 gene with EGR 1 vector could decrease tumor cell migration capabilities significantly after adding TGF-${\beta}1$. These data s howed an important role of EGR 1 in the EMT of non-small-cell lung cancer cells, as well as migration.