Background: Our aim was to identify gaps and limitations in the current literature and to make recommendations for future research required to address these. Materials and Methods: We reviewed occupational exposures and related factors associated with the risk of prostate cancer between 2000 and 2012. These included chemical, ergonomic, physical or environmental, and psychosocial factors which have been reported by epidemiological studies across a range of industries. Results: The results are inconsistent from study to study and generally this is due to the reliance upon the retrospectivity of case-control studies and prevalence (ecological) studies. Exposure assessment bias is a recurring limitation of many of the studies in this review. Conclusions: We consider there is insufficient evidence to implicate prostate cancer risk for ergonomic, physical, environmental or psychosocial factors, but there is sufficient evidence to implicate toxic metals, polychlorinated biphenyls (PCBs) and polycyclic aromatic hydrocarbons (PAHs). More research is required to identify specific pesticides that may be associated with risk of prostate cancer.

Poly (lactic-co-glycolic acid) (PLGA) is one of the most effective biodegradable polymeric nanoparticles (NPs). It has been approved by the US FDA to use in drug delivery systems due to controlled and sustained-release properties, low toxicity, and biocompatibility with tissue and cells. In the present review, the structure and properties of PLGA copolymers synthesized by ring-opening polymerization of DL-lactide and glicolide were characterized using 1H nuclear magnetic resonance spectroscopy, gel permeation chromatography, Fourier transform infrared spectroscopy and differential scanning calorimetry. Methods of preparation and characterization, various surface modifications, encapsulation of diverse anticancer drugs, active or passive tumor targeting and different release mechanisms of PLGA nanoparticles are discussed. Increasing experience in the application of PLGA nanoparticles has provided a promising future for use of these nanoparticles in cancer treatment, with high efficacy and few side effects.

The actual burden of head and neck cancer in India is much greater than reflected through the existing literature and hence can be regarded as a 'tip of iceberg' situation. This has further been evident by the recent reports of 'Net-based Atlas of Cancer in India'. South-east Asia is likely to face sharp increases of over 75% in the number of cancer deaths in 2020 as compared to 2000. Since the percentage increase of Indian population has been nearly twice that of the world in last 15 years there is a likelihood of increase in cancer burden with the same proportion. The distribution of population based cancer registries is grossly uneven with certain important parts of the country being not represented at all and hence the current cancer burden is not reflected by registry data. However, the pathetic situation of health care system in major parts of the country as also emphasized by the World Bank, is not suitable to provide anywhere near accurate data on cancer burden. Head and neck cancer (including thyroid lesions) is third most common malignancy seen in both the sexes across the globe but is the commonest malignancy encountered in Indian males. Also oral cavity cancer is the most prevalent type amongst the males and one of the highest across the globe. This article reviews the latest global and national situation with an especial emphasis on head and neck cancer. Furthermore this review focuses on burden in different sub sites at national and global levels.

Colorectal cancer (CRC) is the third most common malignancy and fourth most common cause of cancer mortality worldwide. Untreated chronic inflammation in the intestine ranks among the top three high-risk conditions for colitis-associated colorectal cancer (CAC). Signal Transducer and Activator of Transcription 3 (STAT3) protein is a member of the STAT family of transcription factors often deregulated in CRC. In this review, we try to emphasize the critical role of STAT3 in CAC as well as the crosstalk of STAT3 with inflammatory cytokines, nuclear factor (NF)-${\kappa}B$, PI3K/Akt, Mammalian Target of Rapamycin (mTOR), Notch, $Wnt/{\beta}$-catenin and microRNA (MiR) pathways. STAT3 is considered as a primary drug target to treat CAC in humans and rodents. Also we updated the findings for inhibitors of STAT3 with regard to effects on tumorigenesis. This review will hopefully provide insights on the use of STAT3 as a therapeutic target in CAC.

Background: The skin is the largest body organ that regulates excretion of metabolic waste products, temperature, and plays an important role in body protection against environmental physical and chemical, as well as biological factors. These include agents that may act as oxidants or catalysts of reactions producing reactive oxygen species (ROS), reactive nitrogen species (RNS), and other oxidants in skin cells. An increased amount of the oxidants, exceeding the antioxidant defense system capacity is called oxidative stress, leading to chronic inflammation, which, in turn, can cause collagen fragmentation and disorganization of collagen fibers and skin cell functions, and thus contribute to skin diseases including cancer. Moreover, research suggests that oxidative stress participates in all stages of carcinogenesis. We report here a summary of the present state of knowledge on the role of oxidative stress in pathogenesis of dermatologic diseases, defensive systems against ROS/RNS, and discuss how physical activity may modulate skin diseases through effects on oxidative stress. The data show duality of physical activity actions: regular moderate activity protects against ROS/RNS damage, and endurance exercise with a lack of training mediates oxidative stress. These findings indicate that the redox balance should be considered in the development of new antioxidant strategies linked to the prevention and therapy of skin diseases.

Although mammography is the primary imaging modality for the breast, it has its limitations especially with dense breast parenchyma. Breast magnetic resonance imaging (MRI) has evolved into an important adjunctive tool as it is currently the most sensitive technique for breast cancer detection. Despite this high sensitivity, overlap in the appearances of some benign and malignant breast lesions results in additional unnecessary intervention with negative results. These false positives, in addition to high cost and limited availability, necessitate establishing proper indications for breast MRI. The literature was here reviewed for recent clinical trials, meta-analyses and review papers which have studied this important subject. PubMed; the US national library of medicine, was utilized to review the literature in the last twenty years. Using the obtained information, current uses of breast MRI are discussed in this paper to determine the indications which are relevant to clinical practice.

The recent discovery of tiny microRNAs (miRNAs) has brought about awareness of a new class of regulators of diverse pathways in many physiological and pathological processes, such as tumorigenesis. They modulate gene expression by targeting plethora of mRNAs, mostly reducing the protein yield of a targeted mRNA. With accumulation of information on characteristics of miR-205, complex and in some cases converse roles of miR-205 in tumor initiation, progression and metastasis are emerging. miR-205 acts either as an oncogene via facilitating tumor initiation and proliferation, or in some cases as a tumor suppressor through inhibiting proliferation and invasion. The aim of this review is to discuss miR-205 roles in different types of cancers. Given the critical effects of deregulated miR-205 on processes involved in tumorigenesis, they hold potential as novel therapeutic targets and biomarkers.

Colorectal cancer is one of the most prevalent diseases all over the world. Early screening and start of chemotherapy is effective in decreasing mortality. This type of cancer can be controlled to some extent via a healthy diet rich in fruit and vegetables. Ginseng is a plant which has been consumed as a herbal medicine for thousands of years in Asian countries. Several in vitro and in vivo studies have shown that this plant not only reduces the incidence of colorectal cancer, but also improves patient's status by enhancing the effects of chemotherapy drugs. However, further studies are needed to prove this relationship. We briefly review ginseng and its components such as ginsenosides reported anticancer effects and their mechanisms of action. Understanding these relationships may produce insights into chemical and pharmacological approaches for enhancing the chemo preventive effects of ginsenosides and for developing novel anticancer agents.

Few studies have examined reasons why those with low socioeconomic status do not adequately receive cancer screening. We therefore conducted a qualitative study to assess the barriers to cancer screening in people with low socioeconomic status, and to examine the reasons why Medical Aid Program (MAP) recipients do not participate in the National Cancer Screening Program (NCSP). A focus group methodology was used. Participants included MAP recipients (men aged 45-79 years, women aged 35-79 years) who had been invited to cancer screening at least twice based on the NCSP protocol, but had not been screened for any cancer from 2009-2012. We recruited participants living in the cities of Goyang and Paju. A total of 23 MAP recipients participated in four focus group discussions, including 12 men and 11 women. In this qualitative study, we identified six barriers to screening: lack of trust in the NCSP and cancer screening units; fear of being diagnosed with cancer; discomfort or pain from the screening procedure; lack of time, lack of knowledge about cancer screening or lack of awareness of the existence of the NCSP; physical disability or underlying disease; and logistic barriers. Interventions such as individualized counseling, letters and reminders, or other individually-targeted strategies, especially for those with lower socioeconomic status are required to increase participation and reduce disparities in cancer screening.

Background: NF-${\kappa}B$ inhibits apoptosis through induction of antiapoptotic proteins and suppression of proapoptotic genes. Various chemotherapy agents induce NF-${\kappa}B$ translocation and target gene activation. We conducted the present study to assess the predictive value of NF-${\kappa}B$ regarding pathologic responses after receiving neoadjuvant chemotherapy. Materials and Methods: We enrolled 131 patients with locally advanced invasive ductal breast carcinoma. Immunohistochemistry (IHC) was used to detect NF-${\kappa}B$ expression. Evaluation of pathologic response was elaborated with the Ribero classification. Results: Expression of NF-${\kappa}B$ was significantly associated with poor pathological response (p=0.02). From the multivariate analysis, it was found that the positive expression of NF-${\kappa}B$ yielded RR=1.74 (95%CI 0.77 to 3.94). Conclusions: NF-${\kappa}B$ can be used as a predictor of poor pathological response after neoadjuvant chemotherapy.

Background: Reproductive cancers are those that affect the human organs that are involved in producing offspring. An attempt is made in the present communication to assess the magnitude and pattern of reproductive cancers, including their treatment modalities, in India. The cancer incidence data related to reproductive cancers collected by five population-based urban registries, namely Bangalore, Bhopal, Chennai, Delhi and Mumbai, for the years 2006-08 were utilized. The reproductive cancers among females constituted around 25% of the total and around 9% among males. Among females, the three major contributors were cervix (55.5%), ovary (26.1%) and corpus uteri (12.4%). Similarly among males, the three major contributors were prostate (77.6%), penis (11.6%) and testis (10.5%). For females, the AAR of reproductive cancers varied between 30.5 in the registry of Mumbai to 37.3 in the registry of Delhi. In males, it ranged between 6.5 in the registry of Bhopal to 14.7 in the registry of Delhi. For both males and females, the individual reproductive cancer sites showed increasing trends with age. The leading treatment provided was: radio-therapy in combination with chemo-therapy for cancers of cervix (48.3%) and vagina (43.9%); surgery in combination with chemo-therapy (54.9%) for ovarian cancer; and surgery in combination with radio-therapy for the cancers of the corpus uteri (39.8%). In males, the leading treatment provided was hormone-therapy for prostate cancer (39.6%), surgery for penile cancer (81.3%) and surgery in combination with chemo-therapy for cancer of the testis (57.6%).

Chronic liver diseases, including cancer, are characterized by inflammation and elevated serum ferritin (SF). However, the causal-relationship remains unclear. This study used primary rat hepatic stellate cells (HSC) as a model to investigate effects of physiological SF concentrations (10, 100 and 1000 pM) because HSCs play a central role in the development and progression of liver fibrosis. Physiological concentrations of SF, either horse SF or human serum, induced pro-inflammatory cytokine $IL1{\beta}$, IL6 and $TNF{\alpha}$ secretion in rat activated HSCs (all p<0.05). By contrast, treatment did not alter activation marker ${\alpha}SMA$ expression. The presence of SF markedly enhanced expression of Grp78 mRNA (p<0.01). Furthermore, transient knock down of Grp78 by endotoxin EGF-SubA abolished SF-induced $IL1{\beta}$ and $TNF{\alpha}$ secretion in activated HSCs (all p<0.05). In conclusion, our results showed that at physiological concentrations SF functions as a pro-inflammatory mediator in primary rat HSCs. We also provide a molecular basis for the action of SF and identified Grp78-associated ER stress pathways as a novel potential therapeutic target for resolution of fibrosis and possible prevention of liver cancer.

Objectives: Dendritic cell (DC)-based tumor immunotherapy needs an immunogenic tumor associated antigen (TAA) and an effective approach for its presentation to lymphocytes. In this study we explored whether transduction of DCs with lentiviruses (LVs) expressing the human interleukin-12 gene could stimulate antigen-specific cytotoxic T cells (CTLs) against human lung cancer cells in vitro. Methods: Peripheral blood monocyte-derived DCs were transduced with a lentiviral vector encoding human IL-12 gene (LV-12). The anticipated target of the human IL-12 gene was detected by RT-PCR. The concentration of IL-12 in the culture supernatant of DCs was measured by ELISA.Transduction efficiencies and CD83 phenotypes of DCs were assessed by flow cytometry. DCs were pulsed with tumor antigen of lung cancer cells (DC+Ag) and transduced with LV-12 (DC-LV-12+Ag). Stimulation of T lymphocyte proliferation by DCs and activation of cytotoxic T-lymphocytes (CTL) stimulated by LV-12 transduced DCs pulsed with tumor antigen against A549 lung cancer cells were assessed with methyl thiazolyltetrazolium (MTT). Results: A recombinant lentivirus expressing the IL-12 gene was successfully constructed. DC transduced with LV-12 produced higher levels of IL-12 and expressed higher levels of CD83 than non-transduced. The DC modified by interleukin -12 gene and pulsed with tumor antigen demonstrated good stimulation of lymphocyte proliferation, induction of antigen-specific cytotoxic T lymphocytes and antitumor effects. Conclusions: Dendritic cells transduced with a lentivirus-mediated interleukin-12 gene have an enhanced ability to kill lung cancer cells through promoting T lymphocyte proliferation and cytotoxicity.

Voacanga globosa (Blanco), a plant endemic to the Philippines, is traditionally used especially by indigenous people of Bataan in the treatment of ulcers, wounds and tumorous growths. This study aimed to provide scientific evidence to therapeutic properties by determining cytotoxic and pro-apoptotic activity of HPLC fractions from leaves on HCT116 human colon carcinoma and A549 human lung carcinoma cell lines. Ethanolic extraction was performed on V globosa leaves followed by hexane and ethyl acetate partitioning. Silica gel column chromatography and high performance liquid chromatography (HPLC) produced MP1, MP2 and MP3 fractions. Cytotoxic activity of the fractions was determined through MTT assay against the cancer cell lines HCT116 and A549 and the non-cancer AA8 Chinese hamster ovarian cell line. Pro-apoptotic activities of the most active fractions were further assessed through DAPI staining, TUNEL assay and JC-1 mitochondrial membrane potential assay with HCT116 cells. While the MPI fraction exerted no significant activity against all cell lines tested, MP2 and MP3 fractions demonstrated high toxicity against HCT116 and A549 cells. The MP3 fraction induced formation of apoptotic bodies, condensed DNA and other morphological changes consistent with apoptosis of HCT116 cells and TUNEL assay showed significant increase in DNA fragmentation over time. In these cells, the MP3 fraction also induced mitochondrial membrane destabilization, which is generally associated with the beginning of apoptosis. Phytochemical analysis demonstrated the presence only of saponins and terpenoids in the MP3 fraction. The results indicate that the MP3 fraction exerts cytotoxic activity on HCT116 cells via induction of apoptosis triggered by loss of mitochondrial membrane potential crucial for cell survival.

Background: Esophagus cancer (EC) is among the five most common cancers in both sexes in Iran, with an incidence rate well above world average. Social rank (SR) of individuals and regions are well-known independent predictors of EC incidence. The aim of current study was to assess gender and social disparities in EC incidence across Iran's provinces through 2003-2009. Materials and Methods: Data on distribution of population at province level were obtained from the Statistical Centre of Iran. Age-standardized incidence rates of EC were gathered from the National Cancer Registry. The Human Development Index (HDI) was used to assess the province social rank. Rate ratios and Kunst and Mackenbach relative indices of inequality ($RII_{KM}$) were used to assess gender and social inequalities, respectively. Annual percentage change (APC) was calculated using joinpoint regression. Results: EC incidence rate increased 4.6% and 6.5% per year among females and males, respectively. There were no gender disparities in EC incidence over the study period. There were substantial social disparities in favor of better-off provinces in Iran. These social disparities were generally the same between males and females and were stable over the study period. Conclusions: The results showed an inverse association between the provinces' social rank and EC incidence rate in Iran. In addition, I found that, in contrast with international trends, women are at the same risk of EC as men in Iran. Further investigations are needed to explain these disparities in EC incidence across the provinces.

Background: Acute myeloid leukemia (AML) is a fatal hematological malignancy which is resistant to a variety of chemotherapy drugs. Myeloid cell leukemia-1 (Mcl-1), a death-inhibiting protein that regulates apoptosis, has been shown to be overexpressed in numerous malignancies. In addition, it has been demonstrated that the expression level of the Mcl-1 gene increases at the time of leukemic relapse following chemotherapy. The aim of this study was to target Mcl-1 by small interference RNA (siRNA) and analyze its effects on survival and chemosensitivity of acute myeloid leukemia cell line HL-60. Materials and Methods: siRNA transfection was performed with a liposome approach. The expression levels of mRNA and protein were measured by real-time quantitative PCR and Western blot analysis, respectively. Trypan blue assays were performed to evaluate tumor cell growth after siRNA transfection. The cytotoxic effects of Mcl-1 siRNA (siMcl-1) and etoposide were determined using MTT assay on their own and in combination. Apoptosis was quantified using a DNA-histone ELISA assay. Results: Transfection with siMcl-1 significantly suppressed the expression of Mcl-1 mRNA and protein in a time-dependent manner, resulting in strong growth inhibition and spontaneous apoptosis. Surprisingly, pretreatment with siMcl-1 synergistically enhanced the cytotoxic effect of etoposide. Furthermore, Mcl-1 down-regulation significantly increased apoptosis sensitivity to etoposide. No significant biological effects were observed with negative control siRNA treatment. Conclusions: Our results suggest that specific suppression of Mcl-1 by siRNA can effectively induce apoptosis and overcome chemoresistance of leukemic cells. Therefore, siMcl-1 may be a potent adjuvant in leukemia chemotherapy.

The pathogenesis of hepatocellular carcinoma (HCC) related to habitual betel quid (BQ) chewing is unclear. Risk of HCCis increased with adverse hepatic fibrosis. This study aimed to assess the impact of chronic viral hepatitis on adverse hepatic fibrosis in HCC related to BQ chewing. This hospital-based case-control study enrolled 200 pairs of age- and gender-matched patients with HCC and unrelated healthy controls. Serologic hepatitis B surface antigen (HBsAg), antibodies to hepatitis C virus (anti-HCV), ${\alpha}$-fetoprotein (AFP), and surrogate markers for significant hepatic fibrosis were measured. Information on substance-use habits was obtained with a questionnaire. By analysis of surrogate markers for hepatic fibrosis, the prevalence of significant hepatic fibrosis in patients chewing BQ was between 45.8% and 91.7%, whereas that for patients without BQ chewing was between 18.4% and 57.9%. The difference was significant (P <0.05 for each surrogate marker). Multivariate analysis indicated that cirrhosis with Child-Pugh C (odds ratio (OR) = 3.28; 95% confidence interval (CI), 1.29-8.37), thrombocytopenia (OR = 3.92, 95% CI, 1.77-8.68), AFP >400 mg/L (OR = 2.21, 95% CI, 1.05-4.66) and male gender (OR = 4.06, 95% CI, 1.29-12.77) were independent factors associated with habitual BQ chewing. In conclusion, adverse hepatic fibrosis and severe liver damage play important roles in the pathogenesis of BQ-related HCC, which could be aggravated by chronic hepatitis B and hepatitis C. BQ-cessation programs and prevention of chronic HBV/HCV infection are needed to prevent HCC related to BQ chewing.

Objective: This study aimed to explore the expression of tissue factor (TF), protease activated receptor-2 (PAR-2), and matrix metalloproteinase-9 (MMP-9) in the MCF-7 breast cancer cell line and influence on invasiveness. Methods: Stable MCF-7 cells transfected with TF cDNA and with TF ShRNA were established. TF, PAR-2, and MMP-9 protein expression was analyzed using indirect immunofluorescence and invasiveness was evaluated using a cell invasion test. Effects of an exogenous PAR-2 agonist were also examined. Results: TF protein expression significantly differed between the TF cDNA and TF ShRNA groups. MMP-9 protein expression was significantly correlated with TF protein expression, but PAR-2 protein expression was unaffected. The PAR-2 agonist significantly enhanced MMP-9 expression and slightly increased TF and PAR-2 expression in the TF ShRNA group, but did not significantly affect protein expression in MCF-7 cells transfected with TF cDNA. TF and MMP-9 expression was positively correlated with the invasiveness of tumor cells. Conclusion: TF, PAR-2, and MMP-9 affect invasiveness of MCF-7 cells. TF may increase MMP-9 expression by activating PAR-2.

Objective: To explore the efficiency of single application of lobaplatin in tran-scatheter arterial chemoembolization (TACE) for patients with a primary hepatic carcinoma who were unable or unwilling to undergo surgery. Methods: 173 patients with primary hepatic carcinoma diagnosed by imaging or pathology were randomly divided into experimental and control groups and respectively treated with lobaplatin and pirarubicin hydrochloride as chemotherapeutic drugs for TACE. The amount of iodipin was regulated according to the tumor number and size, and then gelatin sponge or polyvinyl alcohol particles were applied for embolisms. The efficiency of treatment in the two groups was compared with reference to survival time and therapeutic response. Results: The experimental group (single lobaplatin as chemotherapy drug) was superior to control group (single pirarubicin hydrochloride as chemotherapy drug) in the aspects of survival time and therapeutic response, with statistical significance. Conclusions: Single lobaplatin can be as a chemotherapy drug in TACE and has better efficiency in the aspects of mean survival time and therapeutic response, deserving to be popularized in the clinic.

Background: Cervical cancer is the third commonest type of cancer among women in Malaysia. Our aim was to determine the distribution of human papilloma virus (HPV) genotypes in cervical cancer in our multi-ethnic population. Materials and Methods: This was a multicentre study with a total of 280 cases of cervical cancer from 4 referral centres in Malaysia, studied using real-time polymerase chain reaction (qPCR) detection of 12 high risk-HPV genotypes. Results: Overall HPV was detected in 92.5% of cases, in 95.9% of squamous cell carcinomas and 84.3%of adenocarcinomas. The five most prevalent high-risk HPV genotypes were HPV 16 (68.2%), 18 (40%), 58 (10.7%), 33 (10.4%) and 52 (10.4%). Multiple HPV infections were more prevalent (55.7%) than single HPV infections (36.8%). The percentage of HPV positive cases in Chinese, Malays and Indians were 95.5%, 91.9% and 80.0%, respectively. HPV 16 and 18 genotypes were the commonest in all ethnic groups. We found that the percentage of HPV 16 infection was significantly higher in Chinese (75.9%) compared to Malays (63.7%) and Indians (52.0%) (p<0.05), while HPV 18 was significantly higher in Malays (52.6%) compared to Chinese (25.0%) and Indians (28%) (p<0.05). Meanwhile, HPV 33 (17.9%) and 52 (15.2%) were also more commonly detected in the Chinese (p<0.05). Conclusions: This study showed that the distribution of HPV genotype in Malaysia is similar to other Asian countries. Importantly, we found that different ethnic groups in Malaysia have different HPV genotype infection rates, which is a point to consider during the implementation of HPV vaccination.

Background: The epidermal growth factor receptor (EGFR) mutation status of lung cancer is important because it means that EGFR-tyrosine kinase inhibitor treatment is indicated. The purpose of this prospective study is to determine whether EGFR mutation status could be identified with reference to preoperative factors. Materials and Methods: One hundred-forty eight patients with lung cancer (111 adenocarcinomas, 25 squamous cell carcinomas and 12 other cell types) were enrolled in this study. The EGFR mutation status of each lung cancer was analyzed postoperatively. Results: There were 58 patients with mutant EGFR lung cancers (mutant LC) and 90 patients with wild-type EGFR lung cancers (wild-type LC). There were significant differences in gender, smoking status, maximum tumor diameter in chest CT, type of tumor shadow, clinical stage between mutant LC and wild-type LC. EGFR mutations were detected only in adenocarcinomas. Maximum standardized uptake value (SUVmax:$3.66{\pm}4.53$) in positron emission tomography-computed tomography of mutant LC was significantly lower than that ($8.26{\pm}6.11$) of wild-type LC (p<0.0001). Concerning type of tumor shadow, the percentage of mutant LC was 85.7% (6/7) in lung cancers with pure ground glass opacity (GGO), 65.3%(32/49) in lung cancers with mixed GGO and 21.7%(20/92) in lung cancers with solid shadow (p<0.0001). For the results of discriminant analysis, type of tumor shadow (p=0.00036) was most significantly associated with mutant EGFR. Tumor histology (p=0.0028), smoking status (p=0.0051) and maximum diameter of tumor shadow in chest CT (p=0.047) were also significantly associated with mutant EGFR. The accuracy for evaluating EGFR mutation status by discriminant analysis was 77.0% (114/148). Conclusions: Mutant EGFR is significantly associated with lung cancer with pure or mixed GGO, adenocarcinoma, never-smoker, smaller tumor diameter in chest CT. Preoperatively, EGFR mutation status can be identified correctly in about 77 % of lung cancers.

Background: With recent progress in health science administration, a huge amount of data has been collected from thousands of subjects. Statistical and computational techniques are very necessary to understand such data and to make valid scientific conclusions. The purpose of this paper was to develop a statistical probability model and to predict future survival times for male breast cancer patients who were diagnosed in the USA during 1973-2009. Materials and Methods: A random sample of 500 male patients was selected from the Surveillance Epidemiology and End Results (SEER) database. The survival times for the male patients were used to derive the statistical probability model. To measure the goodness of fit tests, the model building criterions: Akaike Information Criteria (AIC), Bayesian Information Criteria (BIC), and Deviance Information Criteria (DIC) were employed. A novel Bayesian method was used to derive the posterior density function for the parameters and the predictive inference for future survival times from the exponentiated Weibull model, assuming that the observed breast cancer survival data follow such type of model. The Markov chain Monte Carlo method was used to determine the inference for the parameters. Results: The summary results of certain demographic and socio-economic variables are reported. It was found that the exponentiated Weibull model fits the male survival data. Statistical inferences of the posterior parameters are presented. Mean predictive survival times, 95% predictive intervals, predictive skewness and kurtosis were obtained. Conclusions: The findings will hopefully be useful in treatment planning, healthcare resource allocation, and may motivate future research on breast cancer related survival issues.

Objective: The objective of this study was to establish a program model for use in wide-spread cervical cancer screening. :Methods: Cervical cancer screening was conducted in Zhongshan city in Guangdong province, China through a coordinated network of multiple institutes and hospitals. A total of 43,567 women, 35 to 59 years of age, were screened during regular gynecological examinations using the liquid-based ThinPrep cytology test (TCT). Patients who tested positive were recalled for further treatment. Results: The TCT-positive rate was 3.17%, and 63.4% of these patients returned for follow-up. Pathology results were positive for 30.5% of the recalled women. Women who were younger than 50 years of age, urban dwelling, low-income, had a history of cervical disease, began having sex before 20 years of age, or had sex during menstruation, were at elevated risk for a positive TCT test. The recall rate was lower in women older than 50 years of age, urban dwelling, poorly educated, and who began having sex early. Ahigher recall rate was found in women 35 years of age and younger, urban dwelling, women who first had sex after 24 years of age, and women who had sex during menstruation. The positive pathology rate was higher in urban women 50 years of age and younger and women who tested positive for human papillomavirus. Conclusion: An effective model for large-scale cervical cancer screening was successfully established. These results suggest that improvements are needed in basic education regarding cervical cancer screening for young and poorly educated women. Improved outreach for follow-up is also necessary to effectively control cervical cancer.

Resveratrol has been examined in several model systems for potential effects against cancer. Adenosine monophosphate-activated protein kinase (AMPK) is reported to suppress proliferation in most eukaryocyte cells. Whether resveratrol via AMPK inhibits proliferation of oesophageal adenocarcinoma cells (OAC) is unknown. The aim of this study was to determine the roles of AMPK in the protective effects of resveratrol in OAC proliferation and to elucidate the underlying mechanisms. Treatment of cultured OAC derived from human subjects or cell lines with resveratrol resulted in decreased cell proliferation. Further, inhibition of AMPK by pharmacological reagent or genetical approach abolished resveratrol-suppressed OAC proliferation, reduced the level of $p27^{Kip1}$, a cyclin-dependent kinase inhibitor, and increased the levels of S-phase kinase-associated protein 2 (Skp2) of $p27^{Kip1}$-E3 ubiquitin ligase and 26S proteasome activity reduced by resveratrol. Furthermore, gene silencing of $p27^{Kip1}$ reversed resveratrol-suppressed OAC proliferation. In conclusion, these findings indicate that resveratrol inhibits Skp2-mediated ubiquitylation and 26S proteasome-dependent degradation of $p27^{Kip1}$ via AMPK activation to suppress OAC proliferation.

Objective: The purpose of the study was to evaluate clinical value of dual-phase $^{18}F$-FDG SPECT with serum procalcitonin (PCT) in identifying cancers in patients with fever of unknown origin (FUO). Methods: PCT test and dual-phase $^{18}F$-FDG SPECT were sequentially performed on 50 consecutive patients with FUO. Two radiologists evaluated all $^{18}F$-FDG SPECT data independently. A consensus was reached if any difference of opinions existed. Final diagnosis was based on a comprehensive analysis of results for the PCT test, dual-phase $^{18}F$-FDG SPECT and bacterial cultivation, regarded as a gold standard. Results: Among 50 patients, 34 demonstrated PCT ${\geq}0.5{\mu}g/L$. Coincidence imaging showed in 37 patients with inflammatory lesions, and 13 with malignancy. Finally, 36 bacterial, 1 fungal and 1 viral infections, as well as 12 cancerous fevers were confirmed by dual-phase $^{18}F$-FDG SPECT with PCT, combined with bacterial cultivation and clinical follow-up. Conclusion: Our study demonstrated that dual-phase $^{18}F$-FDG SPECT in association with PCT could be a valuable tool for diagnosis in tumor patients with FUO.

Background: Emergency departments are visited by cancer patients for palliation of cancer-related symptoms, management of treatment-related side effects, oncologic emergencies, co-morbidities, and/or end of life care. In this study, we aimed to identify the characteristics of cancer patients admitted to an emergency medicine department in Southwest Turkey. Materials and Methods: In this retrospective descriptive study, a total of 304 emergency department admissions of 102 patients with cancer due to medical conditions were evaluated. Descriptive statistical methods, statistical analysis for correlation, Student's t-test, chi-square tests and logistic regression test were used. Results: The majority of patients visiting to emergency departments were male (n=66, 65%) and over 65 years of age (53, 52%). Some 30% (n=31) had a lung cancer diagnosis, 32% (n=33) presentation with dyspnea, 53% (n=55) with metastasis, 30% (n=16) with multiple metastatic lesions in lung, and 68% (n=70) had a poor ECOG performance status (score 3 to 4). Conclusions: Emergency departments have valuable roles in managing and caring for patients with malignancies.

Background: Tumor length in patients with esophageal cancer (EC) has recently received great attention. However, its prognostic role for EC is controversial. The purpose of our study was to characterize the prognostic value of tumor length in EC patients and offer the optimum cut-off point of tumor length by reliable statistical methods. Materials and Methods: A retrospective analysis was conducted on 71 consecutive patients with EC who underwent surgery. ROC curve analysis was used to determine the optimal cut-off point for tumor length, measured with a handheld ruler after formalin fixation. Correlations between tumor length and other factors were surveyed, and overall survival (OS) rates were compared between the two groups. Potential prognostic factors were evaluated by univariate Kaplan-Meier survival analysis. A P value less than 0.05 was considered significant. Results: There were a total of 71 patients, with a male/female divide of 43/28 and a median age of 59. Characteristics were as follows: squamous/adenocarcinoma, 65/6; median tumor length, 4 (0.9-10); cut-off point for tumor length, 4cm. Univariate analysis prognostic factors were tumor length and modality of therapy. One, three and five year OS rates were 84, 43 and 43% for tumors with ${\leq}4cm$ length, whereas the rates were 75, 9 and 0% for tumors >4 cm. There was a significant association between tumor length and age, sex, weight loss, tumor site, histology, T and N scores, differentiation, stage, modality of therapy and longitudinal margin involvement. Conclusions: Future studies for modification of the EC staging system might consider tumor length too as it is an important prognostic factor. Further assessment with larger prospective datasets and practical methods (such as endoscopy) is needed to establish an optimal cut-off point for tumor length.

The main objective of palliative treatment for cancer patients has been to maintain, if not improve, the quality of life (QoL). There is a lack of local data on satisfaction and QoL among cancer patients receiving palliative treatment in Malaysia. This study covers patients with incurable, progressive cancer disease receiving palliative treatment in a teaching hospital in Kuala Lumpur, comparing the different components of QoL and correlations with patient satisfaction. A cross-sectional survey using Malay validated SF36 QoL and PSQ-18 (Short Form) tools was carried out between July 2012 -January 2013 with 120 cancer patients receiving palliative treatment, recruited into the study after informed consent using convenient sampling. Results showed that highest satisfaction were observed in Communication Aspect ($50.6{\pm}9.07$) and the least in General Satisfaction ($26.4{\pm}5.90$). The Mental Component Summary ($44.9{\pm}6.84$) scored higher when compared with the Physical Component Summary ($42.2{\pm}7.91$). In this study, we found that patient satisfaction was strongly associated with good quality of life among cancer patients from a general satisfaction aspect (r=0.232). A poor significant negative correlation was found in Physical Component (technical quality, r=-0.312). The Mental Component showed there was a poor negative correlation between time spent with doctor (r=-0.192) and accessibility, (r=-0.279). We found that feeling at peace and having a sense of meaning in life were more important to patients than being active or achieving good physical comfort. More studyis needed to investigate patients who score poorly on physical and mental component aspects to understand their needs in order to achieve better cancer care.

Objective: To evaluate the safety and efficacy of sequential transcatheter arterial chemoembolization (TACE) and portal vein embolization (PVE) before major hepatectomy for patients with hepatocellur carcinoma (HCC). Methods: In this retrospective case-control study, data were collected from patients who underwent sequential TACE and PVE prior to major hemihepactectomy. Liver volumes were measured by computed tomography volumetry before TACE, and preoperation to assess degree of future remnant liver (FRL) hypertrophy and to check whether intro- or extrohepatic metastasis existed. Liver function was monitored by biochemistry after TACE, prior to and after major hepatectomy. Results: Mean average FRL volume increased 32.3-71.4% (mean 55.4%) compared with preoperative FRL volume. After TACE, liver enzymes were elevated, but returned to normal in four weeks. During PVE and resection, no patient had intro- or extrohepatic metastasis. Conclusion: Sequential TACE and PVE is an effective method to improve resection opportunity, expand the scope of surgical resection, and greatly reduce postoperative intra- and extrahepatic metastasis.

Purpose: Anastomotic leakage (AL) is associated with high morbidity and mortality, high reoperation rates, and increased hospital length of stay. Here we investigated the risk factors for AL after anterior resection for rectal cancer with a double stapling technique. Patients and Methods: Data for 460 patients who underwent primary anterior resection with a double stapling technique for rectal carcinoma at a single institution from 2003 to 2007 were prospectively collected. All patients experienced a total mesorectal excision (TME) operation. Clinical AL was defined as the presence of leakage signs and confirmed by diagnostic work-up according to ICD-9 codes 997.4, 567.22 (abdominopelvic abscess), and 569.81 (fistula of the intestine). Univariate and logistic regression analyses of 20 variables were undertaken to determine risk factors for AL. Survival was analysed using the Cox regression method. Results: AL was noted in 35 (7.6%) of 460 patients with rectal cancer. :Median age of the patients was 65 (50-74) and 161 (35%) were male. The diagnosis of AL was made between the 6th and 12th postoperative day (POD; mean 8th POD). After univariate and multivariate analysis, age (p=0.004), gender (p=0.007), tumor site (p<0.001), preoperative body mass index (EMI) (p<0.001), the reduction of TSGF on 5th POD less than 10U/ml (p=0.044) and the pH value of pelvic dranage less than or equal to 6.978 on 3rd POD (p<0.001) were selected as 6 independent risk factors for AL. It was shown that significant differences in survival of the patients were AL-related (p<0.001), high ASA score related (p=0.036), high-level EMI related (p=0.007) and advanced TNM stage related

Objective: Connections between chronic inflammation and tumor development and progression are now generally accepted. Recent evidence indicates that hepatitis B is associated with several types of cancer, but whether endometrial carcinoma (EC) is included has not been reported. Methods: We analyzed HBV serum marker status in 398 patients with endometrial cancer, comparing them to 788 control women undergoing health examination. Results: The total prevalence of HBsAg tested positive in cancer group was significantly higher than the control group (12.8% vs 6.0%, P=0.001), while positive HBsAb was significantly lower (41.2% vs 68.5%, P=0.001). Hepatitis B carriers in endometrial cancer group were also more frequent than in the control group (9.3% vs 5.5%, P=0.013). Interestingly, in the endometrial cancer group, 147 cases were HBV serum marker negative, which was also higher than in the control group (36.9% vs 15.6%, P=0.001). Conclusion: There may be a correlation between HBV infection and endometrial carcinoma.

Background: This study was carried out to investigate the interaction of p53 codon 72 polymorphism, dietary and tobacco habits with reference to risk of stomach cancer in Mizoram, India. A total of 105 histologically confirmed stomach cancer cases and 210 age, sex and ethnicity matched healthy population controls were included in this study. Materials and Methods: The p53 codon 72 polymorphism was detected by PCR-RFLP and sequencing. H. pylori infection status was determined by ELISA. Information on various dietary and tobacco related habits was recorded with a standard questionnaire. Results: This study revealed that overall, the Pro/Pro genotype was significantly associated with a higher risk of stomach cancer (OR, 2.54; 95%CI, 1.01-6.40) as compared to the Arg/Arg genotype. In gender stratified analysis, the Pro/Pro genotype showed higher risk (OR, 7.50; 95%CI, 1.20-47.0) than the Arg/Arg genotype among females. Similarly, the Pro/Pro genotype demonstrated higher risk of stomach cancer (OR, 6.30; 95%CI, 1.41-28.2) among older people (>60 years). However, no such associations were observed in males and in individuals <60 years of age. Smoke dried fish and preserved meat (smoke dried/sun dried) consumers were at increased risk of stomach cancer (OR, 4.85; 95%CI, 1.91-12.3 and OR, 4.22; 95%CI, 1.46-12.2 respectively) as compared to non-consumers. Significant gene-environment interactions exist in terms of p53 codon 72 polymorphism and stomach cancer in Mizoram. Tobacco smokers with Pro/Pro and Arg/Pro genotypes were at higher risk of stomach cancer (OR, 16.2; 95%CI, 1.72-153.4 and OR, 9.45; 95%CI, 1.09-81.7 respectively) than the non-smokers Arg/Arg genotype carriers. The combination of tuibur user and Arg/Pro genotype also demonstrated an elevated risk association (OR, 4.76; 95%CI, 1.40-16.21). Conclusions: In conclusion, this study revealed that p53 codon 72 polymorphism and dietary and tobacco habit interactions influence stomach cancer development in Mizoram, India.

Background: Having been known as a virulent disease in 1970s, cancer is now onsidered a chronic disease and 64% of cancer patients live for five years after diagnosis. Home care has gradually gained more importance and it is a great burden on the shoulders of caregivers. Caregivers have to undertake the responsibility of the cancer patient's home management, and organize care and arrange health care services according to the ever-changing condition of patients. Caregivers should be prepared for home care so they can provide accurate and complete care to patients. This descriptive study aims to investigate challenges that caregivers encounter in the home care of patients and the reasons for these challenges. Materials and Methods: The research group consisted of caregivers of outpatients in a daily treatment center in a university hospital. The research sampling consisted of 137 voluntary caregivers of patients who attended the Daily Treatment Center for control, chemotherapy or other supportive cares services between January-June, 2011. Data were collected with face-to-face interviews in the Daily Treatment Center. Ethics Committee approval was taken university hospital; caregivers and their patients were informed about the research and their approval was taken as well. Results: It was found that 54.01% of caregivers help patient's nutrition, 50.36% help medicine use, 26.28% help oral hygiene, 26.28% help to meet urinary needs and 51.82% help to change clothes, 69.34% of caregivers help to change bed sheets, 38.69% help the patient to communicate with their environment and 71.53% help to bring the patient to hospital or outside. Conclusions: This study, it was found that caregivers experience challenges due to following factors: patient nutrition, medicine use, oral and body hygiene, colostomy maintenance and stomach tube feeding, concern of dropping the patient, feeling incompetency in body temperature and fever control, fatigue, and lack of personal time.

Objective: To observe the short-term efficacy, long-term survival time and adverse responses with nedaplatin (NDP) or cisplatin (DDP) concomitant with other chemotherapy in treating non-small cell lung cancer. Materials and Methods: A retrospective, randomized, control study was conducted, in which 619 NSCLC patients in phases III and IV who were initially treated and re-treated were randomly divided into an NDP group (n=294) and a DDP group (n=325), the latter being regarded as controls. Chemotherapeutic protocols (CP/DP/GP/NP/TP) containing NDP or DDP were given to both groups. Patients in both groups were further divided to evaluate the clinical efficacies according to initial and re-treatment stage, pathological pattern, type of combined chemotherapeutic protocols, tumor stage and surgery. Results: The overall response rate (ORR) and disease control rate (DCR) in the NDP group were 48.6% and 95.2%, significantly higher than in the DDP group at 35.1% and 89.2%, respectively (P<0.01). In NSCLC patients with initial treatment, squamous carcinoma and phase III, there were significant differences in ORR and DCR between the groups (P<0.05), while ORR was significant in patients with adenocarcinoma, GP/TP and in phase IIIa (P<0.05). There was also a significant difference in DCR in patients in phase IIIb (P<0.05). According to the statistical analysis of survival time of all patients and of those in clinical phase III, the NDP group survived significantly longer than the DDP group (P<0.01). The rates of decreased hemoglobin and increased creatinine, nausea and vomiting in the NDP group were evidently lower than in DDP group (P<0.05). Conclusion: NDP concomitant with other chemotherapy is effective for treating NSCLC, with higher clinical efficacy than DDP concomitant with chemotherapy, with advantages in prolonging survival time and reducing toxic and adverse responses.

Background: In recent years a wide variety of flavonoids or polyphenolic substances have been reported to possess substantial anti-carcinogenic and antimutagenic activities. Grape proanthocyanidins (GPC) are considered as good examples for which there is evidence of potential roles as anti-carcinogenic agents. Methods: A xenograft model was established using H22 cells subcutaneously injected into mice and used to assess different concentrations of grape proanthocyanidins (GPC) and Endostar. Treatments were maintained for 10 days, then levels of vascular endothelial growth factor (VEGF) and microvessel density (MVD) were examined by immunohistochemistry, while VEGF mRNA was determined by real-time PCR in tumor tissue. Results: The expression of MVD and VEGF decreased gradually as the concentration of GPC increased.There was a significant positive correlation between MVD and VEGF. Conclusions: These results suggest that GPC restrains the growth of tumor, possibly by inhibiting tumour angiogenesis.

Objective: To investigate the effects of abnormal Savda Munziq (ASMq) total phenolics combined with cisplatin and docetaxel on the Hela cell growth. Methods: In vivo cultured Hela cells were treated with cisplatin, docetaxel, total phenolics, cisplatin+total phenolics or docetaxel+total phenolics. MTT was performed to assess inhibition of cell proliferation, flow cytometry to detect apoptosis, and semi-quantitative RT-PCR to test for survivin and Bcl-2 expression. Results: The total phenolics, cisplatin and docetaxel had significant inhibitory and apoptosis-promoting effects on Hela cells (P<0.05), with the early apoptotic rates of $12.8{\pm}0.70%$, $18.9{\pm}3.79%$ and $15.8{\pm}3.8%$; the total phenolics, cisplatin and docetaxel significantly decreased the expression of Bcl-2 and survivin (all P<0.01), especially when used in combination. Conclusion: ASMq total phenolics, combined with cisplatin and docetaxel, could promote the apoptosis of Hela cells possibly through reducing the expression of Bcl-2 and survivin.

Background: Purple rice has become a natural product of interest which is widely used for health promotion. This study investigated the preventive effect of purple rice extract (PRE) mixed diet on DMH initiation of colon carcinogenesis. Materials and Methods: Rats were fed with PRE mixed diet one week before injection of DMH (40 mg/kg of body weight once a week for 2 weeks). They were killed 12 hrs after a second DMH injection to measure the level of $O^6$-methylguanine and xenobiotic metabolizing enzyme activities. Results: In rats that received PRE, guanine methylation was reduced in the colonic mucosa, but not in the liver, whereas PRE did not affect xenobiotic conjugation, with reference to glutathione-S-transferase or UDP-glucuronyl transferase. After 5 weeks, rats that received PRE with DMH injection had fewer ACF in the colon than those treated with DMH alone. Interestingly, a PRE mixed diet inhibited the activity of bacterial ${\beta}$-glucuronidase in rat feces, a critical enzyme for free methylazoxymethanol (MAM) release in the rat colon. These results indicated that purple rice extract inhibited ${\beta}$-glucuronidase activity in the colonic lumen, causing a reduction of MAM-induced colonic mucosa DNA methylation, leaded to decelerated formation of aberrant crypt foci in the rat colon. Conclusions: The supplemented purple rice extract might thus prevent colon carcinogenesis by the alteration of the colonic environment, and thus could be further developed for neutraceutical products for colon cancer prevention.

Smoking is recognized as a health problem worldwide and there is an established tobacco epidemic in Saudi Arabia as in many other countries, with tobacco users at increased risk of developing many diseases. This cross sectional study was conducted to assess the prevalence of oral mucosal, potentially malignant or malignant, lesions associated with tobacco use among a stratified cluster sample of adults in Jeddah, Saudi Arabia. A sample size of 599 was collected and each participant underwent clinical conventional oral examination and filled a questionnaire providing information on demographics, tobacco use and other relevant habits. The most common form of tobacco used was cigarette smoking (65.6 %) followed by Shisha or Moasel (38.1%), while chewing tobacco, betel nuts and gat accounted for 21-2%, 7.7%, and 5% respectively. A high prevalence (88.8%) of soft tissue lesions was found among the tobacco users examined, and a wide range of lesions were detected, about 50% having hairy tongue, 36% smoker's melanosis, 28.9% stomatitis nicotina, 27% frictional keratosis, 26.7% fissured tongue, 26% gingival or periodontal inflammation and finally 20% leukodema. Suspicious potentially malignant lesions affected 10.5% of the subjects, most prevalent being keratosis (6.3%), leukoplakia (2.3%), erythroplakia (0.7%), oral submucous fibrosis (0.5%) and lichenoid lesions (0.4%), these being associated with male gender, lower level of education, presence of diabetes and a chewing tobacco habit. It is concluded that smoking was associated with a wide range of oral mucosal lesions, those suspicious for malignancy being linked with chewable forms, indicating serious effects.

Aim: To study the contribution of genetic variation in RAD51 to risk of esophageal squamous cell carcinoma (ESCC). Methods: Three single nucleotide polymorphisms (SNPs) in RAD51 (rs1801320, rs4144242 and rs4417527) were genotyped in 316 ESCC patients and 316 healthy controls in Anyang area of China using PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism). Demographic variables between cases and controls were statistically compared by T test and Chi-square test. Hardy-Weinberg equilibrium was evaluated by the Chi-square test. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to measure any association with ESCC. Haplotype frequencies were estimated by Phase 2.1. Result: The genotype frequencies of rs1801320, rs4144242 and rs4417527 in patients with ESCC demonstrated no significant differences from those in control group (P>0.05). When the haplotypes of these three SNPs were constructed and their relationships with ESCC risk investigated, however, CGG was observed to increase the risk (P=0.020, OR=2.289). Conclusions: There was no association between the three SNPs of RAD51 and ESCC susceptibility in our Chinese population. However, the CGG haplotype might be a risk factor.

Fangchinoline (Fan) inhibits cell proliferation and induces apoptosis in several cancer cell lines. The effects of Fan on cell growth and proliferation in breast cancer cells remain to be elucidated. Here, we show that Fan inhibited cell proliferation in the MDA-MB-231 breast cancer cell line through suppression of the AKT/Gsk-3beta/cyclin D1 signaling pathway. Furthermore, Fan induced apoptosis by increasing the expression of Bax (relative to Bcl-2), active caspase 3 and cytochrome-c. Fan significantly inhibited cell proliferation of MDA-MB-231 cells in a concentration and time dependent manner as determined by MTT assay. Flow cytometry analysis demonstrated that Fan treatment of MDA-MB-231 cells resulted in cell cycle arrest at the G1 phase, which correlated with apparent downregulation of both mRNA and protein levels of both PCNA and cyclin D1. Further analysis demonstrated that Fan decreased the phosphorylation of AKT and GSK-3beta. In addition, Fan up-regulated active caspase3, cytochrome-c protein levels and the ratio of Bax/Bcl-2, accompanied by apoptosis. Taken together, these results suggest that Fan is a potential natural product for the treatment of breast cancer.

Objectives: TCR-gamma-delta+T cells (${\gamma}{\delta}$ T cells) are non-conventional T lymphocytes that can recognize and eradicate tumor cells. Our previous studies showed that infiltration and function of ${\gamma}{\delta}$ T cells were substantially attenuated in hepatocellular carcinoma (HCC). However, their prognostic value was not clarified. Methods: The association between ${\gamma}{\delta}$ T cells and the clinical outcomes was determined by immunohistochemistry (IHC) in a HCC patient cohort (n = 342). Results:Immunohistochemistry showed decreased infiltration of ${\gamma}{\delta}$ T cells in tumoral tissues compared with paired peritumoral tissues. The counts of ${\gamma}{\delta}$ T cells in peritumoral tissues were negatively correlated with tumor size (P = 0.005). Survival analysis showed that the levels of peritumoral ${\gamma}{\delta}$T cells were related to both time to recurrence (TTR) and overall survival (OS) (P = 0.010 and P = 0.036, respectively) in univariate analysis, and related to TTR in multivariate analysis (P = 0.014, H.R. [95% CI] = 0.682 [0.502-0.927]). Furthermore, the level of peritumoral ${\gamma}{\delta}$ T cells showed independent prognostic value for TTR in Barcelona Clinic Liver Cancer (BCLC) stage A patients (P = 0.038, H.R. [95% CI] = 0.727 [0.537-0.984]). However, tumoral ${\gamma}{\delta}$ T cells did not show independent prognostic value for either TTR or OS in HCC patients. Conclusions: Low counts of ${\gamma}{\delta}$ T cells in peritumoral liver tissue are related to a higher incidence of recurrence in HCC and can predict postoperative recurrence, especially in those with early-stage HCC.

Background: Although the cause in most cases of childhood leukemia is not known, the contribution of environmental risk factors in the context of genetic predisposition has been reported with inconsistent results. The aim of this study was to examine association of childhood leukemia with maternal factors especially during pregnancy, to help in avoiding risk factors. Materials and Methods: This case-control study included children younger than 18 years diagnosed with leukemia from 2008 to 2012. Controls were randomly selected and individually matched to cases with respect to age, sex, and residency. All variables were compared between cases and control to determine any significant association with leukemia. Results: Statistically significant associations between risk of childhood leukemia with mother's education (p=0.001), occupation (p=0.0005) and pesticides exposure (p=0.005) during pregnancy were found. However, there were no significant links with maternal age (p=0.090), history of fetal loss (0.85), history of radiography during pregnancy (p=0.400), history of drug intake (p=0.689) and infection (p=0.696) during pregnancy. Conclusions: The results showed increased risk of leukemia in children whose mothers were working in agriculture and were exposed to pesticides during pregnancy. The further study needs to be investigated to know association of various maternal risk factors with leukemia which remained unknown in this study.

Crude extracts or phytochemicals obtained from some plants have potential anti-cancer properties. Teucrium persicum is an Iranian endemic plant belonging to the Lamiaceae family which has traditionally been used to relieve abdominal pains. However, the anti-cancer properties of this species of the Teucrium genus have not been investigated previously. In this study, we have used a highly invasive prostate cancer cell line, PC-3, which is an appropriate cell system to study anti-tumor properties of plants. A methanolic extract obtained from T persicum potently inhibited viability of PC-3 cells. The viability of SW480 colon and T47D breast cancer cells was also significantly decreased in the presence of the T persicum extract. Flow cytometry suggested that the reduction of cell viability was due to induction of apoptosis. In addition, the results of wound healing and gelatin zymography experiments supported anti-cell invasion activity of T persicum. Interestingly, sublethal concentrations of T persicum extract induced an epithelial-like morphology in a subpopulation of cells with an increase in E-Cadherin and ${\beta}$-Catenin protein levels at the cell membrane. These results strongly suggest that T persicum is a plant with very potent anti-tumor activity.

Background: This study aimed to examine possible effects of implementing a national query program on site-specific cancer mortality rates. Materials and Methods: A total of 2,874 query letters were sent out by the Department of Statistics, Ministry of Health and Welfare of Taiwan between January 2009 and December 2011 to medical certifiers who reported "neoplasm with uncertain nature" on the death certificate asking for more detailed information for coding. Results: Of the 2,571 responses, in 1,398 cases (54%) medical certifiers were still unable to determine the nature of the neoplasm. There were four neoplasm sites for which more than 50% of the responses changed the category to malignant, the gastrointestinal system (73%), urinary system (60%), stomach (55%) and rectum (53%). The liver was the cancer site that showed the largest absolute increase in the number of deaths after the query; however, the brain showed the largest relative increase, at 12%. Conclusions: Different neoplasm sites showed different magnitudes of change in nature after the query. Brain cancer mortality rates exhibited the largest increase.

We screened a small molecular library that was designed and independently synthesized in vitro and found a new drug (MY-03-01) that is active against ovarian cancer. We established that MY-03-01 effectively inhibited SKOV-3 cell survival in a dose-dependent manner, based on cell viability rates, and that it not only induced SKOV-3 apoptosis by itself, but also did so synergistically with paclitaxel. Secondly, when MY-03-01 was applied at $40{\mu}M$, its hemolytic activity was less than 10%, compared with the control, and there was almost no damage to nor mal cells at this concentration. In addition, we used DAPI staining and flow cytometry to show that MY-03-01 could significantly induce apoptosis of SKOV-3 cells. Finally, we found that MY-03-01 likely induced SKOV-3 apoptosis by activating caspase3 and caspase9 through the mitochondrial pathway.

The IL-16 rs4778889 T/C polymorphism is associated with cancer risk. However, the results are conflicting. We performed this meta-analysis to derive a more precise estimation of the relationship. A comprehensive literature search was performed using PubMed, Embase and Web of Science databases. Odds ratio (OR) and 95% confidence interval (CI) were used to assess the strength of association. A total of 6 studies including 1,603 cases and 2,342 controls were identified. With all studies involved, results showed no statistically significant association between IL-16 rs4778889 T/C polymorphism and cancer risk (CC vs. CT+TT: OR=0.74, 95%CI:0.55-1.02, $P_h=0.15$; CC+CT vs. TT: OR=0.89, 95%CI: 0.72-1.10, $P_h=0.03$; CC vs. TT: OR=0.73, 95%CI: 0.53-1.00, $P_h=0.08$; CT vs. TT: OR=0.91, 95%CI: 0.79-1.05, $P_h=0.08$; C vs. T: OR=0.89, 95%CI: 0.74-1.07, $P_h=0.02$). In addition, the results were not changed when studies were stratified by cancer type. However, to verify our findings, it is essential to perform more well-designed studies with larger sample sizes in the future.

Background: The clinical course of the neoplasm may vary due to both patient and tumor cell characteristics. Aim: The aim of this study was to research the influence of certain clinical and pathological features on the prognosis of early stage breast cancer. Materials and Methods: This study included 117 women that were treated and followed-up in between the years 2001-2011. The demographic, clinical and histopathological features of the cases were reviewed retrospectively. Statistical analysis: In categorical comparisons between groups, cross-tab statistics were provided and significance levels were estimated using chi-square test. Cox regression analysis, Pearson and Spearman correlation tests, and the Kaplan-Meier test were also used. Results: With an average of 35-months follow-up, the mean disease-free survival of patients was 91 months and the mean overall survival time was 132 months. In the whole study group, the disease-free survival rates were 88, 84, 83 and 52%, while the overall survival rates 95, 94, 83, and 83% within the first, third, fifth and tenth years, respectively. The disease-free and overall survival rates were decreased with increasing tumor grades, though this was not statistically significant. The presence of lymphovascular invasion, positive staining with Ki67 and postmenopausal status were associated with shorter disease-free and overall survival times. In multivariate analysis, only age and Her2/neu receptor status influenced the prognosis significantly. Conclusions: In parallel to clinical, histopathological, and immunohistochemical prognostic features in breast cancer, in this study positive Her2/neu receptor status, a previously accepted poor prognostic factor, was found to have positive influence after trastuzumab treatment.

Aims: To describe our institutional experience with high dose rate (HDR) interstitial brachytherapy (IBT) compared with previously reported results on the low dose rate (LDR) practice for head and neck cancer. Materials and Methods: Eighty-four patients with oral cavity (n=70) or oropharyngeal cancer (n=14) were treated with 192Ir HDR-IBT. Seventy-eight patients had stage I or II tumour. The patients treated with IBT alone (n=42) received 39-42 Gy/10-14 fractions (median=40 Gy/10 fractions). With respect to the combination therapy group (n=42), prescription dose comprised of 12-18 Gy/3-6 fractions (median=15 Gy/5 fractions) for IBT and 40-50 Gy/20-25 fractions (median=50 Gy/25 fractions) for external radiotherapy. Brachytherapy was given as 2 fractions per day 6 hours apart with 4 Gy per fraction for monotherapy and 3 Gy per fraction for combination therapy. Results: Four patients were not evaluable in the analysis of outcome. The primary site relapse rates were 23.8% (10/42) and 68.4% (26/38) in patients treated with IBT alone and combination therapy, respectively (p<0.001). Salvage surgery was performed in 19 patients. The 5-year local control rate was estimated at 62% and the disease-free survival (DFS) rate at 52% for all patients. Local control with respect to T1 and T2 tumours was 84% and 42%, respectively. Conclusions: Our present series on HDR-IBT and the previous report on LDR-IBT for head and neck cancer demonstrated similar DFS rates at 5 years (52%). The rate of regional failure in node-negative patients was <20% in both of our series. HDR-IBT offers similar results to LDR-IBT for head and neck cancer.

Objective: The aim was to evaluate roles of vitamin D3 (VD3) and beta-carotene (BC) in the development of esophageal squamous cell carcinoma (ESCC) in a high-risk area, Huai'an District, Huai'an City, China. Methods: 100 new ESCC diagnosed cases from 2007 to 2008 and 200 residency- age-, and sex-matched healthy controls were recruited. Data were collected from questionnaires, including a food frequency questionnaire (FFQ) to calculate the BC intake, and reversed phase high-performance liquid chromatography (RP-HPLC) was used to measure the serum concentrations of BC and VD3. Odds ratios (OR) and 95% confidence intervals (CI) were calculated in conditional logistic regression models. Results: The average dietary intake of BC was $3322.9{\mu}g$ (2032.4-5734.3) in the case group and $3626.8{\mu}g$ (1961.9-5827.9) in control group per capita per day with no significant difference by Wilcoxon test (p>0.05). However, the levels of VD3 and BC in the case group were significantly lower than in the control group (p<0.05). The OR values of the highest quartile and the lowest quartile of VD3 and BC in serum samples were both 0.13. Conclusion: Our results add to the evidence that high circulating levels of VD3 and BC are associated with a reduced risk of ESCC in this Chinese population.

Objective: The purpose of this study was to examine the role of programmed cell death 4 (PDCD4) expression in predicting tumor response to neoadjuvant chemoradiotherapy and outcomes for patients with locally advanced rectal cancer. Methods: Clinicopathological factors and expression of PDCD4 were evaluated in 92 patients with LARC treated with nCRT. After the completion of therapy, 4 cases achieved clinical complete response (cCR), and thus the remaining 88 patients underwent a standardized total mesorectal excision procedure. There were 38 patients (41.3%) with a good response (TRG 3-4) and 54 (58.7%) with a poor one (TRG 0-2). Results: Immunohistochemical staining analyses showed that patients with high expression of PDCD4 were more sensitive to nCRT than those with low PDCD4 expression (P=0.02). High PDCD4 expression before nCRT and good response (TRG3-4) were significantly associated with improved 5-year disease-free survival and 5-year overall survival (P<0.05). Multivariate analysis demonstrated that the pretreatment PDCD4 expression was an independent prognostic factor. Conclusion: Our study demonstrated that high expression of PDCD4 protein is a useful predictive factor for good tumor response to nCRT and good outcomes in patients with LARC.

Background: Predictor factors determining complete response to treatment are still not clearly defined. We aimed to evaluate clinicopathological features, risk factors, treatment responses, and survival analysis of patient with advanced nonseminomatous GCTs (NSGCTs). Materials and Methods: Between November 1999 and September 2011, 140 patients with stage II and III NSGCTs were referred to our institutions and 125 patients with complete clinical data were included in this retrospective study. Four cycles of BEP regimen were applied as a first-line treatment. Salvage chemotherapy and/or high-dose chemotherapy (HDCT) with autologous stem cell transplantation were given in patients who progressed after BEP chemotherapy. Post-chemotherapy surgery was performed in selected patients with incomplete radiographic response and normal tumor markers. Results: The median age was 28 years. For the good, intermediate and poor risk groups, compete response rates (CRR) were, 84.6%, 67.9% and 59.4%, respectively. Extragonadal tumors, stage 3 disease, intermediate and poor risk factors, rete testis invasion were associated with worse outcomes. There were 32 patients (25.6%) with non-CR who were treated with salvage treatment. Thirty-one patients died from GCTs and 94% of them had stage III disease. Conclusions: Even though response rates are high, some patients with GCTs still need salvage treatment and cure cannot be achieved. Non-complete response to platinium-based first-line treatment is a negative prognostic factor. Our study confirmed the need for a prognostic and predictive model and more effective salvage approaches.

Background: Overweight and obesity are recognized as major drivers of cancers including breast cancer. Several cytokines, including interleukin-6 (IL-6), IL-10 and lipocalin 2 (LCN2), as well as dysregulated cell cycle proteins are implicated in breast carcinogenesis. The nuclear, casein kinase and cyclin-dependent kinase substrate-1 (NUCKS-1), is a nuclear DNA-binding protein that has been implicated in several human cancers, including breast cancer. Objectives: The present study was conducted to evaluate NUCKS-1 mRNA expression in breast tissue from obese patients with and without breast cancer and lean controls. NUCKS-1 expression was correlated to cytokine profiles as prognostic and monitoring tools for breast cancer, providing a molecular basis for a causal link between obesity and risk. Materials and Methods: This study included 39 females with breast cancer (G III) that was furtherly subdivided into two subgroups according to cancer grading (G IIIa and G IIIb) and 10 control obese females (G II) in addition to 10 age-matched healthy lean controls (G I). NUCKS-1 expression was studied in breast tissue biopsies by means of real-time PCR (RT-PCR). Serum cytokine profiles were determined by immunoassay. Lipid profiles and glycemic status as well as anthropometric measures were also recorded for all participants. Results: IL-6, IL-12 and LCN2 were significantly higher in control obese and breast cancer group than their relevant lean controls (p<0.05), while NUCKS-1 mRNA expression was significantly higher in the breast cancer group compared to the other groups (p<0.05). Significant higher levels of IL-6, IL-12, and LCN2 as well as NUCKS-1 mRNA levels were reported in G IIIb than G IIIa, and positively correlated with obesity markers in all obese patients. Conclusions: Evaluation of cytokine levels as well as related gene expression may provide a new tool for understanding interactions for three axes of carcinogenesis, innate immunity, inflammation and cell cycling, and hope for new strategies of management.

There is a lot of debate on the relationship between vitamin D receptor polymorphisms and risk of breast cancer. Herein, we quantitatively analyzed the published case-control studies on this relationship by meta-analysis, performing a bibliographic search from Pubmed and CNKI up to July 31, 2013. The included case-control studies for Fok1, Bsm1, Taq1, Apa1, Cdx2 and Poly-A were 16, 19, 20, 10, 4, 6, respectively. Crude and adjusted odd ratios and 95% confidence intervals were calculated to present and compare the strength of any associations. The results of combined analyses indicated that Fok1, Bsm1, Apa1, Cdx2 and Poly-A were not significantly associated with the risk of breast cancer. In contrast, the tt genotype of Taq1 was a modest risk factor for breast cancer development (tt vs. TT: OR = 1.21, 95% CI: 1.01-1.44). To further confirm the above results, adjusted effects for the six polymorphisms were pooled based on adjusted ORs reported in the original studies. Adjusted ORs of Fok1, Apa1, Cdx2 and Poly-A were similar to the crude ORs. However, Bsm1 and Taq1 showed inconsistent results. For Bsm1, OR for BB vs. bb was 0.85, 95% CI: 0.74-0.98; for Taq1, OR for tt vs. TT was 1.03, 95% CI: 0.92-1.15, and not associated with risk. Subgroup analyses for crude ORs showed some association between Bsm1, Taq1 and breast cancer in Caucasians only, but for adjusted ORs, no associations were found. This meta-analysis suggests that the roles that Fok1, Apa1, Cdx2 and Poly-A polymorphisms play in breast cancer risk are negligible, with Bsm1 and Taq1 as possible exceptions. To be conservative, we still assumed that they may play a modest role in determining breast cancer risk. Further studies are needed to validate our findings.

Background: The purpose of this study was to assess the relationship between different sonographic features of papillary thyroid carcinoma (PTC) on high-frequency ultrasound and cervical lymph node metastasis (CLNM). Materials and Methods: We enrolled 548 patients who underwent initial surgery for PTC between May 2011 and December 2012 in our hospital at diagnosis. The sonographic features of 513 PTC nodules in 513 eligible patients, who had single PTC nodules in their thyroid glands, were retrospectively investigated. All patients with a suspect malignant nodule (d<0.5cm) among multiple nodules were initially diagnosed by fine-needle aspiration biopsy (FNAB) to ascertain if the suspect nodule was PTC. The final diagnosis of all the thyroid nodules and existence of CLNM were based on postoperative pathology. Patients were divided into two groups: a positive group with CLNM (224 nodules) and a negative group without CLNM (289 nodules). The following factors were investigated: gender, age, echogenicity, echotexture, size, shape, location, margin, contour, calcification morphology, distance between the nodule and pre- or post-border of the thyroid capsule, vascularity and the differences between the two groups. Results: Correlation analysis showed that shorter distances between the nodule and pre- or postborder of thyroid capsule resulted in greater risk of CLNM (Spearman correlation coefficient=-0.22, p<0.0001). The significant factors in multivariate analysis were age<45yrs, larger size (d>1cm), "wider than tall" shape, extrathyroid extension and mixed flow (internal and peripheral) (p<0.05, OR=0.406, 2.093, 0.461, 1.610, 1.322). Conclusions: Significant sonographic features of PTC nodules in preoperative high-frequency ultrasound are crucial for predicting CLNM.

Background: High risk HPV (HR-HPV) testing has been recommended as an effective tool along with cytology screening in identification of cervical intraepithelial lesions (CINs) and prevention of their progress towards invasive cervical cancer. The aim of this study was to assess the HR-HPV DNA status by Hybrid Capture 2 (HC2) assay in healthy asymptomatic women of North-East India. Materials and Methods: This study examined cervical cell samples of forty three (n=43) healthy women by HC2 assay. A High Risk HPV DNA kit (Qiagen) was used which can detect 13 high risk HPV types: 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and 68. Results: The mean relative light units (RLU) for samples was in the range of 141-5, 94, 619. HR-HPV DNA was confirmed in 16% (7/43) of participant women samples. Among demographic and clinical parameters, menstrual irregularity (p=0.039) and infection history (p=0.028) has shown statistically significant differences between the HR-HPV-positive and negative groups. In the HR-HPV positive group, two women were confirmed for CINs after colposcopy and histopathologic examination. Conclusions: We suggest that there may be an association between irregular menstruation and infection history of the urogenital tract with HR-HPV DNA prevalence in North-East Indian asymptomatic women. HC2 assay can be a valuable tool for HR-HPV screening.

Purpose: This study used receiver operating characteristic curve to analyze Surveillance, Epidemiology and End Results (SEER) ependymoma data to identify predictive models and potential disparity in outcome. Materials and Methods: This study analyzed socio-economic, staging and treatment factors available in the SEER database for ependymoma. For the risk modeling, each factor was fitted by a Generalized Linear Model to predict the outcome ('brain and other nervous systems' specific death in yes/no). The area under the receiver operating characteristic curve (ROC) was computed. Similar strata were combined to construct the most parsimonious models. A random sampling algorithm was used to estimate the modeling errors. Risk of ependymoma death was computed for the predictors for comparison. Results: A total of 3,500 patients diagnosed from 1973 to 2009 were included in this study. The mean follow up time (S.D.) was 79.8 (82.3) months. Some 46% of the patients were female. The mean (S.D.) age was 34.4 (22.8) years. Age was the most predictive factor of outcome. Unknown grade demonstrated a 15% risk of cause specific death compared to 9% for grades I and II, and 36% for grades III and IV. A 5-tiered grade model (with a ROC area 0.48) was optimized to a 3-tiered model (with ROC area of 0.53). This ROC area tied for the second with that for surgery. African-American patients had 21.5% risk of death compared with 16.6% for the others. Some 72.7% of patient who did not get RT had cerebellar or spinal ependymoma. Patients undergoing surgery had 16.3% risk of death, as compared to 23.7% among those who did not have surgery. Conclusion: Grading ependymoma may dramatically improve modeling of data. RT is under used for cerebellum and spinal cord ependymoma and it may be a potential way to improve outcome.

Objective: Desmogleins (DSGs) are major members among the desmosomal cadherins critically involved in cell-cell adhesion and the maintenance of normal tissue architecture in epithelia. Reports exploring links of DSG family member expression with cancers are few and vary. The aim of this study was to investigate the ratio of DSG2 and DSG3 mRNA expression in esophageal squamous cell carcinoma (ESCC) tissue to normal tissue (T/N ratio) and evaluate correlations with clinical parameters. Methods: The mRNA expression of DSGs, as well as ${\gamma}$-catenin and desmoplakin, was detected by real-time quantitative RT-PCR in 85 cases of ESCC tissue specimens. Results: The expression level of DSG3 mRNA was significantly higher than that of DSG2 in ESCC specimens (p=0.000). DSG3 mRNA expression highly correlated with histological grade (p=0.009), whereas that of DSG2 did not significantly relate to any clinicopathologic parameter. Kaplan-Meier survival analysis showed that only DSG3 expression had an impact on the survival curve, with negative DSG3 expression indicating worse survival (p=0.038). Multivariate Cox regression analysis demonstrated DSG3 to be an independent prognostic factor for survival. Furthermore, correlation analysis demonstrated the mRNA level of DSG3 to highly correlate with those of ${\gamma}$-catenin and desmoplakin in ESCC samples (p=0.000), implying that the expression of desmosomal components might be regulated by the same upstream regulatory molecules. Conclusions: Our findings suggest that DSG3 may be involved in the progression of ESCC and serve as a prognostic marker, while expression of DSG2 cannot be used as a predictor of ESCC patient outcome.

Objective: To evaluate risk factors for gallstones after gastrectomy. Methods: To identify documents published from 1990 to 2011 the Pubmed, Cochrane Library, Springer Link, CBM and WanFang databases were searched and a meta-analysis was performed with RevMan 5.2 software for odds ratios and 95%CIs. Results: Fifteen studies were selected for the meta-analysis. The pooled ORs [95%CIs] were 0.56 [0.43, 0.73], (P<0.0001) for digestive tract reconstruction, 0.80 [0.54, 1.17], (P=0.25) for pylorus preservation, 0.33[0.15, 0.75], (P=0.008) for resection scope of stomach, 0.33 [0.15, 0.75], (P=0.008) for lymphadenectomy, and 0.13 [0.05, 0.33], (P<0.0001) for vagotomy. Conclusions: Digestive tract physical reconstruction and vagus nerve preservation can reduce the morbidity of gallstones after gastrectomy. Total gastrectomy can add to the morbidity of galltones as does increasing the degree of lymph node dissection. There was no significant difference in gallstones with or without pylorus preservation.

Background: Prostate cancer is the second leading cause of cancer death in men worldwide. Several factors such as availability of screening tests, and dietary, other lifestyle, environmental and genetic influences contribute to worldwide disparities in prostate cancer incidence and mortality rates. Our aims were to investigate patient characteristics at the time of diagnosis, common treatment strategies employed and survival in an Iranian male population with prostate cancer. Materials and Methods: Archives of Pathology Departments of five referral centers affiliated with the School of Medicine of Shahid Sadoughi University in Yazd province were reviewed. Paraffin-embedded blocks were reviewed by two independent pathologists to confirm the diagnosis. The latest modification of the Gleason Scoring System was adopted to determine pathological grading. Following pathological evaluation, patients were contacted via telephone to acquire information regarding their current status. Results: Pathology blocks were available for 113 patients. However, upon phone contacts, we were unable to determine the survival status in 23 patients (response rate=83%). Therefore, 90 patients were enrolled in the final analysis. The median follow-up time was 6.0 years (ranging from 0.3 to 8.8 years). There were 30 death attributed to prostate cancer in the study group. Kaplan-Meier analysis revealed that patient age at the time of diagnosis was a significant predictor of survival. Another significant predictor of poorer survival was higher tumor grade. Conclusions: Our observations indicate that age and pathological grade can negatively affect survival of individuals with prostate cancer in Iran.

This study was undertaken to compare surgical outcomes and survival rates of patients with the 2009 International Federation of Gynecology and Obstetrics (FIGO) stage IIA1 versus IIA2 cervical cancer treated with radical hysterectomy and pelvic lymphadenectomy (RHPL). Patients with stage IIA cervical cancer undergoing primary RHPL between January 2003 and December 2012 at Chiang Mai University Hospital were retrospectively reviewed. The analysis included clinicopathologic variables, i.e. nodal metastasis, parametrial involvement, positive surgical margins, deep stromal invasion (DSI)), lymph-vascular space invasion (LVSI), adjuvant treatment, and 5-year survival. The chi square test, Kaplan-Meier method and log-rank test were used for statistical analysis. During the study period, 133 women with stage IIA cervical cancer, 101 (75.9 %) stage IIA1, and 32 (24.1 %) stage IIA2 underwent RHPL. The clinicopathologic variables of stage IIA1 compared with stage IIA2 were as follows: nodal metastasis (38.6% vs 40.6%, p=0.84), parametrial involvement (10.9% vs 15.6%, p=0.47), positive surgical margins (31.7% vs 31.3%, p=1.0), DSI (39.6% vs 53.1%, p=0.18), LVSI (52.5% vs 71.9%, p=0.05) and adjuvant radiation (72.3% vs 84.4%, p=0.33). With a median follow-up of 60 months, the 5-year disease-free survival (84.6% vs 88.7%, p=0.67) and the 5-year overall survival (83.4% vs 90.0%, P=0.49) did not significantly differ between stage IIA1 and stage IIA2 cervical cancer. In conclusion, patients with stage IIA1 and stage IIA2 cervical cancer have comparable rates of locoregional spread and survival. The need for receiving adjuvant radiation was very high in both substages. The revised 2009 FIGO system did not demonstrate significant survival differences in stage IIA cervical cancer treated with radical hysterectomy. Concurrent chemoradiation should be considered a more suitable treatment for patients with stage IIA cervical cancer.

This study is aimed to investigate the role of paired boxed gene 1 (PAX1) methylation analysis by methylation-sensitive high-resolution melting (MS-HRM) in the detection of high grade lesions in atypical squamous cells cannot exclude high-grade squamous intraepithelial lesion (ASC-H) and compared its performance with the Hybrid Capture 2 (HC2) human papillomavirus (HPV) test. In our study, 130 cases with a diagnosis of ASC-H from the cervical cytological screening by Thinprep cytologic test (TCT) technique were selected for triage. Their cervical scrapings were collected and evaluated by using PAX1 methylation analysis (MS-HRM) and high-risk HPV DNA test (HC2), followed by colposcopy and cervical biopsy. Chi-square test were used to test the differences of PAX1 methylation or HPV infection between groups. In the detection of CIN2+, the sensitivity, specificity, the PPV, NPV and the accuracy of PAX1 MS-HRM assay and high-risk HPV (HR-HPV) tests were respectively 80.6% vs 67.7%, 94.9% vs 54.5%, 83.3%, vs 31.8%, 94.0% vs 84.4%, and 91.5% vs 57.7%. The PAX1 MS-HRM assay proved superior to HR-HPV testing in the detection of high grade lesions (CIN2+) in ASC-H. This approach could screen out the majority of high grade lesion cases of ASC-H, and thus could reduce the referral rate to colposcopy.

Objectives: The present study aimed to examine the cytogenetic and genetic mutation features of acute myeloid leukemia (AML) in elderly Chinese patients. Methods: A retrospective analysis of cytogenetics and genetic mutations was performed in 113 cases (age range 50-82 years) with de novo AML. Results: The most frequent cytogenetic abnormality was t (15;17) (q22;q21), detected in 10.0% (n = 9) of successfully analyzed cases, followed by t (8;21) (q22;q22) in 8.89% (n = 8), and complex karyotypes in 5.56% (n = 5). Those with complex karyotypes included 4 cases (4.44%) of monosomal karyotypes. The frequencies of NPM1, FLT3-ITD, c-kit, and CEBPA mutations were 27.4% (31/113), 14.5% (16/110), 5.88% (6/102), and 23.3% (7/30), respectively. The complete remission rates of patients in low, intermediate, and high risk groups were 37.5%, 48.6%, and 33.3%, respectively (${\chi}^2$ = 0.704, P = 0.703) based on risk stratification. Conclusion: Cytogenetics and genetic mutations alone may not be sufficient to evaluate the prognoses of elderly AML patients. The search for a novel model that would enable a more comprehensive evaluation of this population is therefore imperative.

Concurrent chemo-radiation (CRT) has been established as the standard of care for non-metastatic loco-regionally advanced nasopharyngeal carcinoma (NPC) but recently the addition of induction chemotherapy in the already established regimen has presented an attractive multidisciplinary approach. This retrospective study was carried out to evaluate the efficacy of induction chemotherapy (IC) followed by CRT for the management of loco-regionally advanced NPC. Between July 2005 and September 2010, 99 patients were treated with cisplatin based IC followed by CRT. Induction chemotherapy included a 2 drug combination; intravenous gemcitabine $1000mg/m^2$ on day 1 and 8 and cisplatin $75mg/m^2$ on day 1 only. Radiotherapy (RT) was given as a phase treatment to a total dose of 70 Gy in 35 fractions. Concurrent cisplatin ($75mg/m^2$) was administered to all patients on days 1, 22 and 43. All patients were evaluated for tumor response and adverse effects after IC and 6 weeks after the completion of the treatment protocol. Statistical analysis was performed using SPSS version 17 and Kaplan Meier estimates were applied to project survival. Median follow-up duration was 20 months. The 5-year overall survival (OS), loco regional control (LRC) and relapse free survival (RFS) rates were 71%, 73% and 50%respectively. Acute grade 4 toxicity related to induction chemotherapy and concurrent chemo-radiation was 4% and 2% respectively, with only 3 toxicity-related hospital admissions. We conclude that induction gemcitabine and cisplatin followed by chemo-radiation is a safe and effective regimen in management of nasopharyngeal carcinoma, meriting further investigation in randomized clinical trials.

Aims: To determine the status of women's perception and attitudes about cervical cancer and their thoughts on Kato's self-sampling device. Materials and Methods: This descriptive research was conducted between July-December 2012 with a study populationof married women older than 18 years. Results: A total of 246 women volunteered, with a mean age of $34.9{\pm}9.22$ (19-52). In the last year, 52.0% had been examined by a gynecologist to address a complaint or for a periodic health check. Of the 118 who had not had a gynecological examination, 42.4% indicated negligence, 26.3% stated the reason was no complaint, 14.4% feared they might receive bad results from the examination, and 8.5% stated that were shy or embarrassed. Of all of the women, 35.0% answered that they had information about cervical cancer, and 0.7% had heard about the HPV vaccine. No one in their families had received the vaccine. Of the women, 28.5% had had a Pap smear, and 71.4% of those had normal results. Of those who had never had a Pap smear, 47.2% had never heard about the test; 18.8% explained the reason for not having a test as shyness or embarrassment with a male doctor. None of the women had heard about Kato's device. Once the women were informed, 73.6% expresseed interest in use; 51.9% answered they could use it and not be embarrassed, 30.9% would use it because they did not have to see a doctor, and 17.1% would use it as it allows them to take a smear in all conditions and whenever they want. Of the women, 60.0% thought that they could not successfully use Kato's device; 40.0% thought that a smear should be taken by a doctor. Conclusions: Most of the women in our population had never had a Pap smear and wanted to use the Kato's device.

Aim: This study was to evaluate the effect of whole brain radiation (WBRT) combined with stereotactic radiotherapy (SRS) versus stereotactic radiotherapy alone for patients with brain metastases using a meta-analysis. Materials and Methods: We searched PubMed, EMBASE, Cochrane Library from their inception up to October 2013. Randomized controlled trials involving whole brain radiation combined with stereotactic radiotherapy versus stereotactic radiotherapy alone for brain metastases were included. Statistical analyses were performed using RevMan5.2 software. Results: Four randomized controlled trials including 903 patients were included. The meta-analysis showed statistically significant lowering of the local recurrence rate (OR=0.29, 95%CI: 0.17~0.49), new brain metastasis rate (OR=0.45, 95%CI: 0.28~0.71) and symptomatic late neurologic radiation toxicity rate (OR=3.92, 95%CI: 1.37~11.20) in the combined group. No statistically significant difference existed in the 1-year survival rate (OR=0.78, 95%CI: 0.60~1.03). Conclusions: The results indicate that whole brain radiotherapy combined with stereotactic radiotherapy has advantages in local recurrence and new brain metastasis rates, but stereotactic radiotherapy alone is associated with better neurological function. However, as the samples included were not large, more high-quality, large-sample size studies are necessary for confirmation.

Chondrosarcomas are malignant cartilage-forming tumors of bone which exhibit resistance to both chemotherapy and radiation treatment. miRNAs have been well demonstrated to regulate gene expression and play essential roles in a variety of biological processes, including proliferation, differentiation, migration, cell cycling and apoptosis. In this study, we obtained evidence that miR-100 acts as a tumor suppressor in human chondrosarcomas. Interestingly, cisplatin resistant chondrosarcoma cells exhibit decreased expression of miR-100 compared with parental cells. In addition, we identified mTOR as a direct target of miR-100. Overexpression of miR-100 complementary pairs to the 3' untranslated region (UTR) of mTOR, resulted in sensitization of cisplatin resistant cells to cisplatin. Moreover, recovery of the mTOR pathway by overexpression of S6K desensitized the chondrosarcoma cells to cisplatin, suggesting the miR-100-mediated sensitization to cisplatin dependent on inhibition of mTOR. In summary, the present studies highlight miR-100 as a tumor suppressor in chondrosarcoma contributing to anti-chemoresistance. Overexpression of miR-100 might be exploited as a therapeutic strategy along with cisplatin-based combined chemotherapy for the treatment of clinical chondrosarcoma patients.

Background: Gestational trophoblastic neoplasia (GTN) is a spectrum of disease with abnormal trophoblastic proliferation. Treatment is based on FIGO stage and WHO risk factor scores. Patients whose score is 12 or more are considered as at extremely high risk with a high likelihood of resistance to first line treatment. Optimal therapy is therefore controversial. Objective: This study was conducted in order to summarize the regimen used for extremely high risk or resistant GTN patients in our institution the in past 10 years. Materials and Methods: All the charts of GTN patients classified as extremely high risk, recurrent or resistant during 1 January 2002 to 31 December 2011 were reviewed. Criteria for diagnosis of GTN were also assessed to confirm the diagnosis. FIGO stage and WHO risk prognostic score were also re-calculated to ensure the accuracy of the information. Patient characteristics were reviewed in the aspects of age, weight, height, BMI, presenting symptoms, metastatic area, lesions, FIGO stage, WHO risk factor score, serum hCG level, treatment regimen, adjuvant treatments, side effects and response to treatment, including disease free survival. Results: Eight patients meeting the criteria of extremely high risk or resistant GTN were included in this review. Mean age was 33.6 years (SD=13.5, range 17-53). Of the total, 3 were stage III (37.5%) and 5 were stage IV (62.5%). Mean duration from previous pregnancies to GTN was 17.6 months (SD 9.9). Mean serum hCG level was 864,589 mIU/ml (SD 98,151). Presenting symptoms of the patients were various such as hemoptysis, abdominal pain, headache, heavy vaginal bleeding and stroke. The most commonly used first line chemotherapeutic regimen in our institution was the VAC regimen which was given to 4 of 8 patients in this study. The most common second line chemotherapy was EMACO. Adjuvant radiation was given to most of the patients who had brain metastasis. Most of the patients have to delay chemotherapy for 1-2 weeks due to grade 2-3 leukopenia and require G-CSF to rescue from neutropenia. Five form 8 patients were still survived. Mean of disease free survival was 20.4 months. Two patients died of the disease, while another one patient died from sepsis of pressure sore wound. None of surviving patients developed recurrence of disease after complete treatment. Conclusions: In extremely high risk GTN patients, main treatment is multi-agent chemotherapy. In our institution, we usually use VAC as a first line treatment of high risk GTN, but since resistance is quite common, this may not suitable for extremely high risk GTN patients. The most commonly used second line multi-agent chemotherapy in our institution is EMA-CO. Adjuvant brain radiation was administered to most of the patients with brain metastasis in our institution. The survival rate is comparable to previous reviews. Our treatment demonstrated differences from other institutions but the survival is comparable. The limitation of this review is the number of cases is small due to rarity of the disease. Further trials or multicenter analyses may be considered.

Two types of nanosized titanium dioxide, anatase ($anTiO_2$) and rutile ($rnTiO_2$), are widely used in industry, commercial products and biosystems. $TiO_2$ has been evaluated as a Group 2B carcinogen. Previous reports indicated that $anTiO_2$ is less toxic than $rnTiO_2$, however, under ultraviolet irradiation $anTiO_2$ is more toxic than $rnTiO_2$ in vitro because of differences in their crystal structures. In the present study, we compared the in vivo and in vitro toxic effects induced by $anTiO_2$ and $rnTiO_2$. Female SD rats were treated with $500{\mu}g/ml$ of $anTiO_2$ or $rnTiO_2$ suspensions by intra-pulmonary spraying 8 times over a two week period. In the lung, treatment with $anTiO_2$ or $rnTiO_2$ increased alveolar macrophage numbers and levels of 8-hydroxydeoxyguanosine (8-OHdG); these increases tended to be lower in the $anTiO_2$ treated group compared to the $rnTiO_2$ treated group. Expression of $MIP1{\alpha}$ mRNA and protein in lung tissues treated with $anTiO_2$ and $rnTiO_2$ was also significantly up-regulated, with $MIP1{\alpha}$ mRNA and protein expression significantly lower in the $anTiO_2$ group than in the $rnTiO_2$ group. In cell culture of primary alveolar macrophages (PAM) treated with $anTiO_2$ and $rnTiO_2$, expression of $MIP1{\alpha}$ mRNA in the PAM and protein in the culture media was significantly higher than in control cultures. Similarly to the in vivo results, $MIP1{\alpha}$ mRNA and protein expression was significantly lower in the $anTiO_2$ treated cultures compared to the $rnTiO_2$ treated cultures. Furthermore, conditioned cell culture media from PAM cultures treated with $anTiO_2$ had less effect on A549 cell proliferation compared to conditioned media from cultures treated with $rnTiO_2$. However, no significant difference was found in the toxicological effects on cell viability of ultra violet irradiated $anTiO_2$ and $rnTiO_2$. In conclusion, our results indicate that $anTiO_2$ is less potent in induction of alveolar macrophage infiltration, 8-OHdG and $MIP1{\alpha}$ expression in the lung, and growth stimulation of A549 cells in vitro than $rnTiO_2$.

Polymorphisms in miRNA binding sites have been shown to affect miRNA binding to target genes, resulting in differential mRNA and protein expression and susceptibility to common diseases. Our purpose was to predict SNPs (single nucleotide polymorphisms) within miRNA binding sites of inflammatory genes in relation to gastric cancer. A complete list of SNPs in the 3'UTR regions of all inflammatory genes associated with gastric cancer was obtained from Pubmed. miRNA target prediction databases (MirSNP, Targetscan Human 6.2, PolymiRTS 3.0, miRNASNP 2.0, and Patrocles) were used to predict miRNA target sites. There were 99 SNPs with MAF>0.05 within the miRNA binding sites of 41 genes among 72 inflammation-related genes associated with gastric cancer. NF-${\kappa}B$ and JAK-STAT are the two most important signaling pathways. 47 SNPs of 25 genes with 95 miRNAs were predicted. CCL2 and IL1F5 were found to be the shared target genes of hsa-miRNA-624-3p. Bioinformatic methods could identify a set of SNPs within miRNA binding sites of inflammatory genes, and provide data and direction for subsequent functional verification research.

Purpose: To explore the value of systemic inflammatory markers as independent prognostic factors and the extent these markers improve prognostic classification for patients with inoperable advanced or metastatic gastric cancer (GC) receiving palliative chemotherapy. Methods: We studied the prognostic value of systemic inflammatory factors such as circulating white blood cell count and its components as well as that combined to form inflammation-based prognostic scores (Glasgow Prognostic Score (GPS), Neutrophil-Lymphocyte Ratio (NLR), Platelet Lymphocyte Ratio (PLR), Prognostic Index (PI) and Prognostic Nutritional Index (PNI)) in 384 patients with inoperable advanced or metastatic gastric cancer (GC) receiving first-line chemotherapy. Univariate and multivariate analyses were performed to examine the impact of inflammatory markers on overall survival (OS). Results: Univariate analysis revealed that an elevated white blood cell, neutrophil and/or platelet count, a decreased lymphocyte count, a low serum albumin concentration, and high CRP concentration, as well as elevated NLR/PLR, GPS, PI, PNI were significant predictors of shorter OS. Multivariate analysis demonstrated that only elevated neutrophil count (HR 3.696, p=0.003) and higher GPS (HR 1.621, p=0.01) were independent predictors of poor OS. Conclusion: This study demonstrated elevated pretreatment neutrophil count and high GPS to be independent predictors of shorter OS in inoperable advanced or metastatic GC patients treated with first-line chemotherapy. Upon validation of these data in independent studies, stratification of patients using these markers in future clinical trials is recommended.

Background: Colorectal cancer (CRC) was the fourth most commonly diagnosed cancer in Iran between 2000 and 2009, with adenocarcinoma (AC) as the most common histological type. Demographic, topographic and histological variables are important in the epidemiology and biology of cancer. The aim of this study was to investigate clinicopathological features of colon adenocarcinomas in Qazvin, Iran. Materials and Methods: With a retrospective design, patient records of two pathology wards from March 1997 to March 2013 were studied with regard to anatomical location and histological classification. A broader anatomical grouping was also used including distal vs proximal regions and right sided vs left sided tumors. Data were analyzed using T-test and chi-square test. Results: 118 (50.9%) male and 114 (49.1%) female patients were included in the study. Mean age was $57.3{\pm}14.7$ years, with 29.2% under 50 years. There was no significant gender difference for age at diagnosis. The rectum (56%) and sigmoid colon (25%) were the most frequent anatomical locations. Proximal cases accounted for 18.6% in males and 8.8% in females (p=0.02). AC was more prevalent than other usual types in younger patients. The proportion of proximal cancer was 1.7% in first eight years of the study period vs 12.1% in the second one (p=0.005). A similar trend was also seen in right sided colon cancers (p=0.018). Conclusions: Young people are also at risk for the cancer with poor prognosis. Screening programs and weight loss in obese individuals can reduce incidence and complications of CRC.

Purpose: With regard to the protective effect of vitamin D against colorectal cancer (CRC), we evaluated genetic variants that might influence vitamin D metabolism: vitamin D receptor (VDR), vitamin D binding protein (GC), vitamin D 25-hydroxylase (CYP2R1), and vitamin D 25-hydroxy 1-alpha hydroxylase (CYP27B1). Materials and Methods: A total of 657 subjects, including 303 cases with CRC and 354 controls were enrolled in this case-control study. All 657 were genotyped for the four gene variants using PCR-RFLP methods. Results: In this study, no significant difference was observed for VDR (rs2238136), GC (rs4588), CYP2R1 (rs12794714), and CYP27B1 (rs3782130) gene variants in either genotype or allele frequencies between the cases with CRC and the controls and this lack of difference remained even after adjustment for age, BMI, sex, smoking status, NSAID use, and family history of CRC. Furthermore, no evidence for effect modification of the variants and CRC by BMI, sex, or tumor site was observed. Conclusions: Our findings do not support a role for VDR, GC, and CYP27B1 genes in CRC risk in our Iranian population. Another interesting finding, which to our knowledge has not been reported previously, was the lack of association with the CYP2R1 gene polymorphism. Nonetheless, our findings require confirmation and possible roles of vitamin D metabolism-related genes in carcinogenesis need to be further investigated.

Previous studies have suggested anti-tumor effects of asiatic acid in some human cancer cell lines. This agent is reported to increase the levels of $p21^{WAF1/CIP1}$ in human breast cancer cell lines. However, the molecular mechanisms have not been established. Here we report that asiatic acid up-regulates $p21^{WAF1/CIP1}$ protein expression but not the level of $p21^{WAF1/CIP1}$ mRNA in HepG2 human hepatoma cells. Furthermore, we found that the asiatic acid induced increase of $p21^{WAF1/CIP1}$ protein was associated with decreased phosphorylation (ser-146) of $p21^{WAF1/CIP1}$. Knockdown of NDR1/2 kinase, which directly phosphorylates $p21^{WAF1/CIP1}$ protein at ser-146 and enhances its proteasomal degradation, increased the levels of $p21^{WAF1/CIP1}$ protein and eliminated the regulation of $p21^{WAF1/CIP1}$ stability by asiatic acid. At the same time, the expression of NDR1/2 kinase decreased during treatment with asiatic acid in HepG2 cells. Moreover, asiatic acid inhibited the proliferation of HepG2 cells, this being attenuated by knockdown of $p21^{WAF1/CIP1}$. In conclusion, we propose that asiatic acid inhibits the expression NDR1/2 kinase and promotes the stability of $p21^{WAF1/CIP1}$ protein through attenuating NDR1/2 dependent phosphorylation of $p21^{WAF1/CIP1}$ in HepG2 cells.

Background: The number of colorectal cancer (CRC) patients in Taiwan has increased in recent years; therefore, the effective dissemination of information related to symptom care has become especially important. Previous studies indicated that the physical and psychological status of cancer patients can be effectively improved by telephone counseling services (TCS). Thus, determining the most effective means of establishing a TCS to support the clinical practice of oncology has become a crucial goal for nursing. The purposes of this study were to analysis the content of the TCS for CRC and explore stratification of the TCS. Materials and Methods: The study design was retrospective. A total of 850 calls were made to CRC patients in the cancer center of Southern Taiwan during the period of January 2007- December 2011. A structure questionnaire was adopted to analysis satisfaction. Results: Responses provided by the TCS included information regarding nutrition, side effects resulting from chemotherapy and pain. Moreover, 28.7% of CRC patients needed advanced treatment. More than 90% satisfaction with all aspects of the calls was found. Conclusions: The TCS coulkd be shown to provide an effective means by which to expand the reach of nursing care to different times, places and patients, allowing for greater cost efficiency and more rapid service.

Cervical cancer is an issue of foremost importance globally, specifically affecting the developing nations. Significant advances have taken place with regard to diagnosis of cervical cancer, especially with screening. Appropriate screening measures can thus reduce the incidence of cervical cancer. The most desirable screening technique should be less invasive, easy to perform, cost-effective and cover a wide range of diagnostic icons. Manual liquid based cytology (MLBC) can be considered as one of the suitable technique for screening with the above-mentioned benefits. The aim of the current study was to compare two cervical screening techniques on the basis of different morphological parameters and staining parameters by using modified acetic acid Pap staining to see the possibility of reducing time economy involved in conventional Pap staining (CPS). The study was conducted on a total 88 cases and all were analyzed with both MLBC and CPS. Forty eight cases that were regarded as satisfactory on the basis of Bethesda system by both methods were further recruited for investigation. Their morphological parameters and staining quality were compared and scored according to a scoring system defined in the study. Quality indices was calculated for both staining procedures and smear techniques.

Nigella sativa (N sativa), commonly known as black seed, has been used in traditional medicine to treat many diseases. The antioxidant, anti-inflammatory, and antibacterial activities of N sativa extracts are well known. Therefore, the present study was designed to investigate the anticancer activity of seed extract (NSE) and seed oil (NSO) of N sativa against a human lung cancer cell line. Cells were exposed to 0.01 to 1 mg/ml of NSE and NSO for 24 h, then percent cell viability was assessed by 3-(4, 5-dimethylthiazol-2yl)-2, 5-biphenyl tetrazolium bromide (MTT) and neutral red uptake (NRU) assays, and cellular morphology by phase contrast inverted microscopy. The results showed NSE and NSO significantly reduce the cell viability and alter the cellular morphology of A-549 cells in a concentration dependent manner. The percent cell viability was recorded as 75%, 50%, and 26% at 0.25, 0.5, and 1 mg/ml of NSE by MTT assay and 73%, 48%, and 23% at 0.25, 0.5, and 1 mg/ml of NSE by NRU assay. Exposure to NSO concentrations of 0.1 mg/ml and above for 24 h was also found to be cytotoxic. The decrease in cell viability at 0.1, 0.25, 0.5, and 1 mg/ml of NSO was recorded to be 89%, 52%, 41%, and 13% by MTT assay and 85%, 52%, 38%, and 11% by NRU assay, respectively. A-549 cells exposed to 0.25, 0.5 and 1 mg/ml of NSE and NSO lost their typical morphology and appeared smaller in size. The data revealed that the treatment of seed extract (NSE) and seed oil (NSO) of Nigella sativa significantly reduce viability of human lung cancer cells.

AMFR, autocrine motility factor receptor, also called gp78, is a cell surface cytokine receptor which has a dual role as an E3 ubiquitin ligase in endoplasmic reticulum-associated degradation. AMFR expression is associated with tumor malignancy. We here investigated the clinical significance of AMFR and its role in metastasis and prognosis in gastric cancer. Expression of AMFR, E-cadherin and N-cadherin in cancer tissues and matched adjacent normal tissues from 122 gastric cancer (GC) patients undergoing surgical resection was assessed by immunohistochemistry. Levels of these molecules in 17 cases selected randomly were also analysed by Western blotting. AMFR expression was significantly increased in gastric cancer tissues, and associated with invasion depth and lymph node metastasis. Kaplan-Meier analysis showed AMFR expression correlated with poor overall survival and an increased risk of recurrence in the GC cases. Cox regression analysis suggested AMFR to be an independent predictor for overall and recurrence-free survival. E-cadherin expression was decreased in gastric cancer tissues; conversely, N-cadherin was increased. Expression of AMFR negatively correlated with E-cadherin expression, whereas N-cadherin expression showed a significant positive correlation with AMFR expression. AMFR might be involved in the regulation of epithelial-mesenchymal transition, with aberrant expression correlating with a poor prognosis and promoting invasion and metastasis in GCs.

Objective: To validate the relationship between MACC1 and 6-phosphofructo-2-kinase/fructose 2, 6 bisphosphatase (PFKFB2) expression as well as its clinicopathological features and prognostic significance in hepatocellular carcinoma. Methods: By using immunohistochemistry, we investigated the MACC1 and PFKFB2 protein expression in 60 pairs of hepatocellular carcinoma and corresponding non-tumor tissues. Using the Mann-Whitney U test, the Chi-square test, Kaplan-Meier survival analysis, Cox proportional hazard regression analysis and Spearman analysis, we studied the relationship between MACC1 and PFKFB2 protein expression and postoperative overall survival (OS) of the HCC patients. Results: MACC1 and PFKFB2 positive staining rates were significantly higher in hepatocellular carcinoma than in the corresponding nontumor tissues (P=0.012 and 0.04, respectively). The clinicopathological features evaluation revealed that positive expression of MACC1 was associated with a high Edmondson classification (P=0.007) and advanced TNM stage (P=0.027). Similar findings were evident for PFKFB2 expression (P=0.002 and P=0.027). MACC1 and PFKFB2 positive expression was associated with a lower OS rate (P=0.004 and 0.03, respectively). Kaplan-Meier survival and Cox proportional hazard regression analyses revealed MACC1 positive expression to be a prognostic factor for postoperative OS, but PFKFB was not. Conclusion: Highly expressed MACC1 and PFKFB2 protein were associated with TNM stage, Edmondson-Steier classification and overall survival. MACC1 may affect tumor metabolism partly through expression and phophorylation of PFKFB2.

Background: A relation between abdominal obesity and colorectal tumor development has been reported repeatedly, and is believed to be more remarkable in man than in women. However, the details vary depending on scientific reports. This may be due at least partly to the selected surface anthropometric index in addition to the influence of gender and ethnic groups. To cope with this, we considered a new index of abdominal obesity and evaluated its risk prediction potential. Materials and Methods: Six hundred ninety five Japanese (262 women and 433 men) who had a colonoscopy were studied. The new index was named as waist circumference to height index (WHI) and was calculated by the formula of waist circumference (cm)/height (m)/height (m). Biochemical and lifestyle factors were investigated preceding the colonoscopy. Statistical analysis was performed using SPSS for Windows. Results: Increase of WHI was associated with altered metabolism of carbohydrate and lipid in both women and men. WHI was positively related with the development of colon tumor of women, while not with that of men. Logistic regression analysis performed for stratified age groups (45-54, 55-64 and 65-74 years) showed that WHI significantly increased odds ratio to 1.31 (CI 1.05-1.64 p=0.01) in women of 55-65 years. In contrast, in men this index WHI reduced the odds ratio insignificantly, while low density lipoprotein and triglyceride significantly increased the odds ratio to 1.01 (CI 1.00-1.03 p=0.02) in the 55-65 year group and to 1.02 (CI 1.00-1.03 p=0.02) in the 45-55 year group. Conclusions: In Japanese the risk factors for colon tumor development are different between women and men. WHI is a simple and efficient predictor of colon tumor risk in Japanese women and may be used to select those who should have colonoscopy.

Background: Soft tissue sarcomas (STS) represent 1% of all malignant lesions. In this study the authors analyzed the incidence of STS in Vojvodina (the north region of Serbia) in the period from 1985 to 2009. A number of studies conducted worldwide indicate that STS incidence rates are tending to increase. Materials and Methods: On the basis of data from the Cancer Registry of Vojvodina, age standardized STS incidence rates were established as well as their linear trend, with data on histological structure, age, gender and STS distribution at specific locations. Results: The total number of registered patients was 1,308. Average age standardized rate was 1.90/100,000 per year. The investigated period showed a slight increase in the incidence rate (average annual percent increase=0.77%). The most frequent histological type was sarcoma not otherwise specified-NOS (27%), followed by leiomyosarcoma (21%), liposarcoma (14%), rhabdomyosarcoma (11%) and malignant fibrous histiocytoma (9%). The male/female ratio was 0.73:1. Every fifth patient was younger than 39. Conclusions: Comparison among eight international STS epidemiology studies show that the incidence rate range is between 1.4/100,000-5.0/100,000, though our finding is closer to the lower limit. Furthermore, the incidence rate increase was lower than that characteristic for the half of the analyzed studies. A partial explanation for that should be looked for among changes in diagnostic criteria and STS classifications.

This study aimed at summarizing published study findings on the diagnostic value of rectal bleeding (RB) and informing clinical practice, preventive interventions and future research areas. We searched Medline and Embase for studies published by September 13, 2013 examining the risk of colorectal cancer in patients with RB using highly inclusive algorithms. Data for sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and positive predictive value (PPV) of RB were extracted by two researchers and analyzed applying Meta-Disc (version 1.4) and Stata (version 11.0). Methodological quality of studies was assessed according to QUADAS. A total of 38 studies containing 5,626 colorectal cancer patients and 73,174 participants with RB were included. The pooled sensitivity and specificity were 0.47 (95% CI: 0.45-0.48) and 0.96 (95% CI: 0.96-0.96) respectively. The overall PPVs ranged from 0.01 to 0.21 with a pooled value of 0.06 (95% CI: 0.05-0.08). Being over the age of 60 years, change in bowel habit, weight loss, anaemia, colorectal cancer among first-degree relatives and feeling of incomplete evacuation of rectum appeared to increase the predictive value of RB. Although RB greatly increases the probability of diagnosing colorectal cancer, it alone may not be sufficient for proposing further sophisticated investigations. However, given the high specificity, subjects without RB may be ruled out of further investigations. Future studies should focus on strategies using RB as an "alarm" symptom and finding additional indications to justify whether there is a need for further investigations.

Background: The purpose of our study was to elucidate the joint effects of combined smoking and alcohol intake on esophageal cancer mortality in Japanese men through a large cohort study with a 20-year follow-up period. Materials and Methods: The Japan Collaborative Cohort Study for Evaluation of Cancer Risk (JACC Study) was established in the late 1980s, including 46,395 men and 64,190 women aged 40 years and older and younger than 80. Follow-up of these participants was conducted until 2009. We used the Cox proportional hazards model to analyze data for 42,408 people excluding female participants, 411 people with histories of malignant neoplasms, and 3,576 with unclear smoking and drinking data. Results: The joint effects of age at start of smoking and amount of alcohol consumed per day were compared with non-smokers and non-drinkers or those consuming less than one unit of alcohol per day. The mortality risk was 9.33 (95% confidence interval, 2.55-34.2) for those who started smoking between ages 10 and 19 years and drinking at least three units of alcohol per day. Regarding the joint effects of cumulative amount of smoking and alcohol intake, the risk was high when both smoking and alcohol intake were above a certain level. Conclusions: In this Japanese cohort study, increased cancer mortality risks were observed, especially for people who both started smoking early and drank alcohol. Quitting smoking or not starting to smoke at any age and reducing alcohol consumption are important for preventing esophageal cancer in Japan.

Aim: To investigate the effect of hyperglycemia and hyperinsulinemia on prostate cancer risk. Materials and Methods: This hospital based study was carried out using data retrieved from the register maintained in the Department of Biochemistry of a tertiary care hospital of Kathmandu, Nepal between $31^{st}$ December, 2011 and $31^{st}$ October, 2013. The variables collected were age, serum cholesterol, serum calcium, PSA, fasting blood glucose, serum insulin. Analysis was performed by descriptive statistics and testing of hypothesis using Excel 2003, R 2.8.0, Statistical Package for the Social Sciences (SPSS) for Windows Version 16.0 (SPSS Inc; Chicago, IL, USA) and the EPI Info 3.5.1 Windows Version. Results: Of the total 125 subjects enrolled in our present study, 25 cases were of PCa and 100 were healthy controls. The mean value of fasting plasma glucose was 95.5 mg/dl in cases of prostatic carcinoma and the mean value of fasting plasma insulin was $5.78{\mu}U/ml$ (p value: 0.0001*). The fasting insulin levels ${\mu}U/ml$ were categorized into the different ranges starting from ${\leq}2.75$, >2.75 to ${\leq}4.10$, >4.10 to ${\leq}6.10$, > $6.10{\mu}U/ml$. The maximum number of cases of prostatic carcinoma of fasting insulin levels falls in range of > $6.10{\mu}U/ml$. The highest insulin levels (> $6.10{\mu}U/ml$) were seen to be associated with an 2.55 fold risk of prostatic carcinoma when compared with fasting insulin levels of (< $2.75{\mu}U/ml$). Conclusions: Elevated fasting levels of serum insulin appear to be associated with a higher risk of prostate cancer.

Aim: To evaluate the operative, oncologic and obstetric outcomes of the loop electrosurgical excision procedure (LEEP) in cases with cervical neoplasia. Materials and Methods: A retrospective cohort study was conducted on patients who were suspected of cervical neoplasia and therefore undergoing LEEP at Siriraj Hospital, Mahidol University, Thailand, during 1995-2000. Outcome measures included operative complications in 407 LEEP patients and long-term outcomes in the 248 patients with cervical intraepithelial neoplasia (CIN) who were treated with only LEEP. Results: There were 407 patients undergoing LEEP; their mean age was $39.7{\pm}10.5$ years. The histopathology of LEEP specimens revealed that 89 patients (21.9%) had lesions ${\leq}CIN$ I, 295 patients (72.5%) had CIN II or III, and 23 patients (5.6%) had invasive lesions. Operative complications were found in 15 patients and included bleeding (n=9), and infection (n=7). After diagnostic LEEP, 133 patients underwent hysterectomy as the definite treatment for cervical neoplasia. Of 248 CIN patients who had LEEP only, seven (2.8%) had suffered recurrence after a median of 16 (range 6-93) months; one had CIN I, one had CIN II, and five had CIN III. All of these recurrent patients achieved remission on surgical treatment with re-LEEP (n=6) or simple hysterectomy (n=1). A significant factor affecting recurrent disease was the LEEP margin involved with the lesion (p=0.05). Kaplan-Meier analysis showed 5-year and 10-year disease-free survival (DFS) estimates of 99.9%. Twelve patients became pregnant a total of 14 times, resulting in 12 term deliveries and two miscarriages - one of which was due to an incompetent cervix. Conclusions: LEEP for patients with cervical neoplasia delivers favorable surgical, oncologic and obstetric outcomes.

Evidence is growing that the $GABA_B$ receptor, which belongs to the G protein-coupled receptor (GPCR) superfamily, is involved in tumorigenesis. Recent studies have shown that ${\beta}$-arrestin can serve as a scaffold to recruit signaling protein c-Jun N-terminal knase (JNK) to GPCR. Here we investigated whether ${\beta}$-arrestin recruits JNK to the $GABA_B$ receptor and facilitates its activation to affect the growth of cancer cells. Our results showed that ${\beta}$-arrestin expression is decreased in breast cancer cells in comparison with controls. ${\beta}$-arrestin could enhance interactions of the $GABA_BR{\cdot}{\beta}-arrestin{\cdot}JNK$ signaling module in MCF-7 and T-47D cells. Further studies revealed that increased expression of ${\beta}$-arrestin enhances the phosphorylation of JNK and induces cancer cells apoptosis. Collectively, these results indicate that ${\beta}$-arrestin promotes JNK mediated apoptosis via a $GABA_BR{\cdot}{\beta}-arrestin{\cdot}JNK$ signaling module.

Background: MicroRNAs (miRNAs) are an abundant class of endogenous small non-coding RNAs of 20-25 nucleotides in length that function as negative gene regulators. MiRNAs play roles in most biological processes, as well as diverse human diseases including cancer. Recently, many studies investigated the association between SNPs in miR-146a rs2910164, miR-196a2 rs11614913, miR-149 rs229283, miR-499 rs3746444 and colorectal cancer (CRC), which results have been inconclusive. Methodology/Principal Findings: PubMed, EMBASE, CNKI databases were searched with the last search updated on November 5, 2013. For miR-196a2 rs11614913, a significantly decreased risk of CRC development was observed under three genetic models (dominant model: OR = 0.848, 95%CI: 0.735-0.979, P = 0.025; recessive model: OR = 0.838, 95%CI: 0.721-0.974, P = 0.021; homozygous model: OR = 0.754, 95%CI: 0.627-0.907, P = 0.003). In the subgroup analyses, miR-$196a2^*T$ variant was associated with a significantly decreased susceptibility of CRC (allele model: OR = 0.839, 95%CI: 0.749-0.940, P = 0.000; dominant model: OR = 0.770, 95%CI: 0.653-0.980, P = 0.002; recessive model: OR = 0.802, 95%CI: 0.685-0.939, P = 0.006; homozygous model: OR = 0.695, 95%CI: 0.570-0.847, P = 0.000). As for miR-149 rs2292832, the two genetic models (recessive model: OR = 1.199, 95% CI 1.028-1.398, P = 0.021; heterozygous model: OR = 1.226, 95% CI 1.039-1.447, P = 0.013) demonstrated increased susceptibility to CRC. On subgroup analysis, significantly increased susceptibility of CRC was found in the genetic models (recessive model: OR = 1.180, 95% CI 1.008-1.382, P = 0.040; heterozygous model: OR = 1.202, 95% CI 1.013-1.425, P = 0.013) in the Asian group. Conclusions: These findings supported that the miR-196a2 rs11614913 and miR-149 rs2292832 polymorphisms may contribute to susceptibility to CRC.

Adiposity is a well-recognized risk factor of type 2 diabetes and cardiovascular disease, and recently there is increasing evidence that excess body weight is an avoidable cause of cancer, including gastrointestinal, endometrial, esophageal adenocarcinoma, colorectal, postmenopausal breast, prostate, and renal malignancies. The mechanisms whereby adiposity is associated with tumor development remains not well understood. There are some most studied hypothesized mechanisms such as, high levels of insulin and free levels of insulin-like growth factors, sex hormones, adipocytokines, and inflammatory cytokines, adiposity-induced hypoxia, and so on. The potential mechanisms and conclusions in adiposity associated with increased risk for developing malignancy, and the underlying cellular and molecular mechanisms will be studied very well in the near future.