Showing papers in "Asian Pacific Journal of Cancer Prevention in 2013"

Epidemiology of Oral Cancer in Asia in the Past Decade- An Update (2000-2012)

Abstract: The prevalence of oral cancers (OC) is high in Asian countries, especially in South and Southeast Asia. Asian distinct cultural practices such as betel-quid chewing, and varying patterns of tobacco and alcohol use are important risk factors that predispose to cancer of the oral cavity. The aim of this review is to provide an update on epidemiology of OC between 2000 and 2012. A literature search for this review was conducted on Medline for articles on OC from Asian countries. Some of the articles were also hand searched using Google. High incidence rates were reported from developing nations like India, Pakistan, Bangladesh, Taiwan and Sri Lanka. While an increasing trend has been observed in Pakistan, Taiwan and Thailand, a decreasing trend is seen in Philippines and Sri Lanka. The mean age of occurrence of cancer in different parts of oral cavity is usually between 51-55 years in most countries. The tongue is the leading site among oral cancers in India. The next most common sites in Asian countries include the buccal mucosa and gingiva. The 5 year survival rate has been low for OC, despite improvements in diagnosis and treatment. Tobacco chewing, smoking and alcohol are the main reasons for the increasing incidence rates. Low socioeconomic status and diet low in nutritional value lacking vegetables and fruits contribute towards the risk. In addition, viral infections, such as HPV and poor oral hygiene, are other important risk factors. Hence, it is important to control OC by screening for early diagnosis and controlling tobacco and alcohol use. It is also necessary to have cancer surveillance at the national-level to collect and utilise data for cancer prevention and control programs.

Long Non-coding RNA GAS5 Functions as a Tumor Suppressor in Renal Cell Carcinoma

Abstract: Background: Renal cell carcinoma (RCC) is a malignancy with a poor prognosis. We aimed to explore whether the expression of Long Non-Coding RNA (LncRNA) growth arrest-specific transcript 5 (GAS5) is associated with RCC genesis. Methods: We selected twelve clinical samples diagnosed for renal clear cell carcinoma and found that the LncRNA GAS5 transcript levels were significantly reduced relative to those in adjacent unaffected normal renal tissues. Results: In addition, expression of GAS5 was lower in the RCC cell line A498 than that in normal renal cell line HK-2. Furthermore, using functional expression cloning, we found that overexpression of GAS5 in A498 cells inhibited cell proliferation, induced cell apoptosis and arrested cell cycling. At the same time, the migration and invasion potential of A498 cells were inhibited compared to control groups. Conclusion: Our study provided the first evidence that a decrease in GAS5 expression is associated with RCC genesis and progression and overexpression of GAS5 can act as a tumor suppressor for RCC, providing a potential attractive therapeutic approach for this malignancy.

Down-regulation of long non-coding RNA TUG1 inhibits osteosarcoma cell proliferation and promotes apoptosis.

Abstract: Objective: To investigate the expression level of TUG1 and one of its transcript variants (n377360) in osteosarcoma cells and assess the role of TUG1 in proliferation and apoptosis in the U2OS cell line. Methods: TUG1 and n377360 expression levels in patients with osteosarcomas and the U2OS human osteosarcoma cell line were evaluated using real-time quantitative PCR. U2OS cells were transected with TUG1 and n377360 siRNA or non-targeting siRNA. MTS was performed to assess the cell proliferation and flow cytometry was applied to analyze apoptosis. Results: We found significantly higher TUG1 and n377360 expression levels in osteosarcoma tissues compared with matched non-tumorous tissues. In line with this, suppression of TUG1 and n377360 expression by siRNA significantly impaired the cell proliferation potential of osteosarcoma cells. Furthermore, inhibition of TUG1 expression significantly promoted osteosarcoma cell apoptosis. Conclusions: The overexpression of TUG1 and n377360 in osteosarcoma specimens and the functional role of TUG1 and n377360 regarding cell proliferation and apoptosis in an osteosarcoma cell line provided evidence that the use of TUG1 or n377360 may be a viable but an as yet unexplored therapeutic strategy in tumors that over express these factors.

Potential targets for prevention of colorectal cancer: a focus on PI3K/Akt/mTOR and Wnt pathways

Abstract: Colorectal cancer (CRC) is one of the most common cancers in many parts of the world. Its development is a multi-step process involving three distinct stages, initiation that alters the molecular message of a normal cell, followed by promotion and progression that ultimately generates a phenotypically altered transformed malignant cell. Reports have suggested an association of the phosphoinositide-3-kinase (PI3K)/Akt pathway with colon tumorigenesis. Activation of Akt signaling and impaired expression of phosphatase and tensin homolog (PTEN) (a negative regulator of Akt) has been reported in 60-70% of human colon cancers and inhibitors of PI3K/Akt signaling have been suggested as potential therapeutic agents. Around 80% of human colon tumors possess mutations in the APC gene and half of the remainder feature β-catenin gene mutations which affect downstream signaling of the PI3K/Akt pathway. In recent years, there has been a great focus in targeting these signaling pathways, with natural and synthetic drugs reducing the tumor burden in different experiment models. In this review we survey the role of PI3K/Akt/mTOR and Wnt signaling in CRC.

Prevalence of Depression in Breast Cancer Survivors: a Systematic Review of Observational Studies

Abstract: Background: Depression is common in breast cancer patients. The aim of this paper was to make a systematic review of its prevalence and associated factors oin breast cancer survivors. Materials and Methods: An extensive systematic electronic review (PUBMED, CINAHL, PsyINFO and Ovid) and handsearch were carried out to retrieve published articles up to November 2012, using Depression OR Dysthymia AND (Cancer OR Tumor OR Neoplasms as the keywords. Information about the design of the studies, measuring scale, characteristics of the participants, prevalence of depression and its associated factors from the included studies were extracted and summarized. Results: We identified 32 eligible studies that recruited 10,826 breast cancer survivors. Most were cross-sectional or prospective designed. The most frequent instrument used to screen depression was the Center for Epidemiological Studies for Depression (CES-D, n=11 studies) followed by the Beck Depression Inventory (BDI, n=6 studies) and the Hospital Anxiety and Depression Scale (HADS, n=6 studies). CES-D returned about similar prevalence of depression (median=22%, range=13-56%) with BDI (median=22%, range=17-48%) but higher than HADS (median=10%, range=1-22%). Depression was associated with several socio-demographic variables, cancer-related factors, treatment-related factors, subject psychological factors, lifestyle factors, social support and quality of life. Conclusions: Breast cancer survivors are at risk for depression so that detection of associated factors is important in clinical practice.

Are neutrophil/lymphocyte and platelet/lymphocyte rates in patients with non-small cell lung cancer associated with treatment response and prognosis?

Abstract: Background: Inflammation is a critical component of tumor progression. Many cancers arise from sites of infection, chronic irritation, and inflammation. It is now becoming clear that the tumour microenvironment, which is largely orchestrated by inflammatory cells, is an essential participant in the neoplastic process, promoting proliferation, survival and migration. Platelets can release some growth factors such as platelet-derived growth factor, platelet factor 4, and thrombospondin. Such factors have been shown to promote hematogenous tumour spread, tumor cell adhesion and invasion, and angiogenesis and to play an important role in tumor progression. In this study, we aimed to investigate effects of the pretreatment neutrophil to lymphocyte ratio (NLR) and the platelet to lymphocyte ratio (PLR) on survival and response to chemoradiotherapy in patients with non-small-cell lung cancer (NSCLC). Materials and Methods: Ninety-four patients with non-metastatic NSCLC were included and separated into two groups according to median valuse of NLR and PLR (low:<3.44 or high:≥3.44 and low:<194 or high≥194, respectively). Results: Pretreatment high NLR and PLR were associated with significantly shorter disease-free and overall survival rates. Multivariate analysis revealed that the overall survival rates were significantly linked with PLR (OR: 1.87, CI: 1.20-2.91, p: 0.006) and response to chemoradiotherapy (OR: 1.80, CI: 1.14-2.81, p: 0.012) and the disease-free survival rates were significantly associated with NLR (OR: 1.81, CI: 1.16-2.82, p: 0.009) and response to chemoradiotherapy (OR: 2.30, CI: 1.45-3.66, p: 0.001). There was no significant difference between patients with high and low NLR in terms of response to chemoradiotherapy. Similarly, there was no significant influence of the PLR. Conclusions: Pretreatment NLR and PLR measurements can provide important prognostic results in patients with NSCLC and assessment of the two parameters together appears to better predict the prognosis in patients with NSCLC. The effect of inflammation, indicators of NLR and PLR, on survival seems independent of the response to chemoradiotherapy.

Burden of Smoked and Smokeless Tobacco Consumption in India - Results from the Global adult Tobacco Survey India (GATS-India)- 2009-2010

Abstract: Background: The Global Adult Tobacco Survey (GATS) was carried out for systematically monitoring tobacco use and for tracking key tobacco control indicators. Materials and Methods: A total of 70,802 households, including 42,647 in rural areas and 28,155 in urban areas, were covered with a three stage sampling design. Data were collected on sociodemographic characteristics, knowledge, attitude and practices of tobacco consumption.Results: GATS-India highlighted that total tobacco use among its residents is overall 34.6%, varying for males (47.9%) and females (20.7%). The rural areas of the country exhibit comparatively higher prevalence rates (38.4%) in comparison to urban areas (25.3%). Overall, Khaini, a smokeless tobacco product (12.0%), is the most popular form of tobacco use among males and females, followed by bidi smoking (9.0%). Conclusion: Results of GATS data can be used as baseline for evaluation of new tobacco control approaches in India integrating culturally acceptable and cost effective measures.

Cruciferous Vegetables: Dietary Phytochemicals for Cancer Prevention

Abstract: Relationships between diet and health have attracted attention for centuries; but links between diet and cancer have been a focus only in recent decades. The consumption of diet-containing carcinogens, including polycyclic aromatic hydrocarbons and heterocyclic amines is most closely correlated with increasing cancer risk. Epidemiological evidence strongly suggests that consumption of dietary phytochemicals found in vegetables and fruit can decrease cancer incidence. Among the various vegetables, broccoli and other cruciferous species appear most closely associated with reduced cancer risk in organs such as the colorectum, lung, prostate and breast. The protecting effects against cancer risk have been attributed, at least partly, due to their comparatively high amounts of glucosinolates, which differentiate them from other vegetables. Glucosinolates, a class of sulphur- containing glycosides, present at substantial amounts in cruciferous vegetables, and their breakdown products such as the isothiocyanates, are believed to be responsible for their health benefits. However, the underlying mechanisms responsible for the chemopreventive effect of these compounds are likely to be manifold, possibly concerning very complex interactions, and thus difficult to fully understand. Therefore, this article provides a brief overview about the mechanism of such compounds involved in modulation of carcinogen metabolising enzyme systems.

Breast Cancer awareness among Saudi females in Jeddah

Abstract: Breast cancer is the most frequent malignancy of women worldwide. It is the leading cause of female cancer related disability and mortality. In Saudi Arabia breast cancer ranks first among cancerous diseases in females. In the Gulf region, and especially in Saudi Arabia, few studies have been conducted to address breast cancer awareness. The purpose of the current study was therefore to investigate the level of breast cancer awareness among Saudi females in Jeddah, focusing on knowledge of breast cancer warning signs, risk factors, screening programs and breast self-examination (BSE). The design of this study was an exploratory correlational analysis. The sample comprised 200 Saudi females aged 20 and older living in Jeddah. Data were collected using face-to- face interviews. Breast cancer awareness was measured using a modified Arabic version of the Breast Cancer Awareness Measure (Breast CAM) version 2. Descriptive statistical analysis, Pearson's Product Moment correlation coefficients and ANOVA test were used to answer study questions. Out of 200 participants, 50.5% were aware of breast lump as a warning sign of breast cancer, 57.5% claimed that family history was risk factor, 20.5% had undergone breast screening, 79% heard about BSE, and 47.5% knew how to perform BSE. Findings indicated that Saudi females level of awareness of breast cancer is very inadequate. Public awareness interventions are needed in order to overcome an ever-increasing burden of this disease among Saudi females.

Association Between C-reactive Protein and Risk of Cancer: A Meta-analysis of Prospective Cohort Studies

Abstract: Background: Associations between elevated C-reactive protein (CRP) and cancer risk have been reported for many years, but the results from prospective cohort studies remains controversial. A meta-analysis of prospective cohort studies was therefore conducted to address this issue. Methods: Eligible studies were identified by searching the PubMed and EMBASE up to October 2012. Pooled hazard ratios (HR) was calculated by using random effects model. Results: Eleven prospective cohort studies involving a total of 194,796 participants and 11,459 cancer cases were included in this meta-analysis. The pooled HR per natural log unit change in CRP was 1.105 (95% confidence interval (CI): 1.033-1.178) for all-cancer, 1.308 (95% CI: 1.097-1.519) for lung cancer, 1.040 (95% CI: 0.910-1.170) for breast cancer, 1.063 (95% CI: 0.965-1.161) for prostate cancer, and 1.055 (95% CI: 0.925-1.184) for colorectal cancer. Dose-response analysis showed that the exponentiated linear trend for a change of one natural log unit in CRP was 1.012 (95% CI: 1.006-1.018) for all-cancer. No evidence of publication bias was observed. Conclusions: The results of this meta-analysis showed that the elevated levels of CRP are associated with an increased risk of all-cancer, lung cancer, and possibly breast, prostate and colorectal cancer. The result supports a role of chronic inflammation in carcinogenesis. Further research effort should be performed to identify whether CRP, as a marker of inflammation, has a direct role in carcinogenesis.

Clinical comparison between paclitaxel liposome (Lipusu®) and paclitaxel for treatment of patients with metastatic gastric cancer.

Abstract: Aim: To compare the efficacy and safety of paclitaxel liposome (Lipusu ® ) with paclitaxel in combination with tegafur and oxaliplatin in treating patients with advanced gastric cancer. Materials and Methods: Patients with advanced gastric cancer receiving chemotherapy were retrospectively collected, and divided into two groups. Patients in group A received paclitaxel liposomes at a dose of 135 mg/m 2 on day 1 of each cycle, and patients in group B were given paclitaxel at the same dose with the same timing. All patients received tegafur at a dose of 500 mg mg/m 2 on days 1-5, and oxaliplatin at a dose of 80-100 mg/m 2 on day 1 for 2 cycles (each cycle was 21 d in total). Results: Fifty-eight patients could be evaluated for efficacy. The overall response rate was 47% in group A (14/30), and 46% in group B (13/28). Disease control rate was 73% in group A (22/30), and 71% in group B (20/28) (P>0.05). No significant differences were detected in hematologic and neurologic toxicities between the two groups (P>0.05). However, nausea, vomiting and hypersensitive reactions were significantly lower in group A than in group B (P<0.05). Conclusion: Paclitaxel liposomes are as effective as paclitaxel when combined with tegafur and oxaliplation in treating patients with advanced gastric cancer, but adverse reactions with paclitaxel liposomes are less common.

miRNA-218 inhibits osteosarcoma cell migration and invasion by down-regulating of TIAM1, MMP2 and MMP9.

Abstract: Deregulated miRNAs participate in osteosarcoma genesis. In this study, the expression of miRNA-218 in human osteosarcomas, adjacent normal tissues and Saos-2 human osteosarcoma cells was first assessed. Then the precise role of miRNA-218 in osteosarcoma cells was investigated. Upon transfection with a miR-218 expression vector, the proliferation of Saos-2 human osteosarcoma cells determined using the ATPlite assay was significantly suppressed, whilw migration of Saos-2 cells detected by wound healing and invasion determined using transwells were dramatically inhibited. Potential target genes of miR-218 were predicted and T-cell lymphoma invasion and metastasis 1 (TIAM1) and matrix metalloproteinase 2 (MMP2) and 9 (MMP9) were identified. This was confirmed by western blotting, which showed that miR-218 expression inhibited TIAM1, MMP2 and MMP9 protein expression. Collectively, these data suggest that miR-218 acts as a tumor suppressor in osteosarcomas by down-regulating TIAM1, MMP2 and MMP9 expression.

Physical activity and its relation to cancer risk: updating the evidence.

Abstract: Scientific evidence for the primary prevention of cancer caused by physical activity of regular moderate-intensity or greater is rapidly accumulating in this field. About 300 epidemiologic studies on the association between physical activity and cancer risk have been conducted worldwide. The objectives of this paper were three-fold: (i) to describe briefly the components of physical activity and its quantification; ( ii) to summarize the most important conclusions available from comprehensive reports, and reviews of the epidemiologic individual and intervention studies on a role physical activity in cancer prevention; (iii) to present proposed biological mechanisms accounting for effects of activity on cancer risk. The evidence of causal linked physical activity and cancer risk is found to be strong for colon cancer - convincing; weaker for postmenopausal breast and endometrium cancers - probable; and limited suggestive for premenopausal breast, lung, prostate, ovary, gastric and pancreatic cancers. The average risk reductions were reported to be 20-30%. The protective effects of physical activity on cancer risk are hypothesized to be through multiple interrelated pathways: decrease in adiposity, decrease in sexual and metabolic hormones, changes in biomarkers and insulin resistance, improvement of immune function, and reduction of inflammation. As there are several gaps in the literature for associations between activity and cancer risk, additional studies are needed. Future research should include studies dealing with limitations in precise estimates of physical activity and of a lack of consensus on what defines sedentary behavior of individuals and those linked with the proposed biomarkers to cancer risk and controlled exercise intervention trials.

Attributable Causes of Liver Cancer Mortality and Incidence in China

Abstract: Objectives: To estimate the proportion of liver cancer cases and deaths due to infection with hepatitis B virus (HBV), hepatitis C virus (HCV), aflatoxin exposure, alcohol drinking and smoking in China in 2005. Study design: Systemic assessment of the burden of five modifiable risk factors on the occurrence of liver cancer in China using the population attributable fraction. Methods: We estimated the population attributable fraction of liver cancer caused by five modifiable risk factors using the prevalence data around 1990 and data on relative risks from meta-analyses, and large-scale observational studies. Liver cancer mortality data were from the 3rd National Death Causes Survey, and data on liver cancer incidence were estimated from the mortality data from cancer registries in China and a mortality/incidence ratio calculated. Results: We estimated that HBV infection was responsible for 65.9% of liver cancer deaths in men and 58.4% in women, while HCV was responsible for 27.3% and 28.6% respectively. The fraction of liver cancer deaths attributable to aflatoxin was estimated to be 25.0% for both men and women. Alcohol drinking was responsible for 23.4% of liver cancer deaths in men and 2.2% in women. Smoking was responsible for 18.7% and 1.0% . Overall, 86% of liver cancer mortality and incidence (88% in men and 78% in women) was attributable to these five modifiable risk factors. Conclusions: HBV, HCV, aflatoxin, alcohol drinking and tobacco smoking were responsible for 86% of liver cancer mortality and incidence in China in 2005. Our findings provide useful data for developing guidelines for liver cancer prevention and control in China and other developing countries.

Cabbage (Brassica oleracea L. var. capitata) Phytochemicals with Antioxidant and Anti-inflammatory Potential

Abstract: Background: The objective of this study was to investigate antioxidant and anti-inflammatory activity of cabbage phytochemicals. Materials and Methods: Color coordinates were evaluated by colorimetry, and the antioxidant and anti-inflammatory activities were analyzed by spectrophotometer for some common cabbage varieties. Results: Red heads had the highest total antioxidant contents followed by Savoy, Chinese and green heads. The Chinese variety had the highest ABTS (2,2-azino-di-(3-ethylbenzthiazoline-sulfonic acid) antioxidant activity, was 5.72 μmol TE/g fw (Trolox equivalent). The green variety had the highest DPPH (free radical scavenging activity) antioxidant activity, which was 91.2 μmol TE/g fw. The red variety had the highest FRAP (ferric reducing antioxidant power) antioxidant activity, which was 80.8 μmol TE/g fw. The total phenol amounts were 17.2–32.6 mM trolox equivalent antioxidant capacity (TEAC) and the total flavonoid amounts were 40.0–74.2 mg quercetin per gram. Methanolic extracts of different cabbage heads showed different anti-inflammatory activity values. Chinese, Savoy and green heads had the highest anti-inflammatory activity, while red heads had the lowest. Conclusions: The results suggest that these varieties of cabbage heads could contribute as sources of important antioxidant and anti-inflammatory related to the prevention of chronic diseases associated to oxidative stress, such as in cancer and coronary artery disease.

Epithelial-mesenchymal Transition and Its Role in the Pathogenesis of Colorectal Cancer

Abstract: Epithelial-to-mesenchymal transition (EMT) is a collection of events that allows the conversion of adherent epithelial cells, tightly bound to each other within an organized tissue, into independent fibroblastic cells possessing migratory properties and the ability to invade the extracellular matrix. EMT contributes to the complex architecture of the embryo by permitting the progression of embryogenesis from a simple single-cell layer epithelium to a complex three-dimensional organism composed of both epithelial and mesenchymal cells. However, in most tissues EMT is a developmentally restricted process and fully differentiated epithelia typically maintain their epithelial phenotype. Recently, elements of EMT, specially the loss of epithelial markers and the gain of mesenchymal markers, have been observed in pathological states, including epithelial cancers. Increasing evidence has confirmed its presence in human colon during colorectal carcinogenesis. In general, chronic inflammation is considered to be one of the causes of many human cancers including colorectal cancer(CRC). Accordingly, epidemiologic and clinical studies indicate that patients affected by ulcerative colitis and Crohn’s disease, the two major forms of inflammatory bowel disease, have an increased risk of developing CRC. A large body of evidence supports roles for the SMAD/STAT3 signaling pathway, the NF-kB pathway, the Ras-mitogenactivated protein kinase/Snail/Slug and microRNAs in the development of colorectal cancers via epithelial-tomesenchymal transition. Thus, EMT appears to be closely involved in the pathogenesis of colorectal cancer, and analysis refered to it can yield novel targets for therapy.

Serum miR-19a Predicts Resistance to FOLFOX Chemotherapy in Advanced Colorectal Cancer Cases

Abstract: Background: Colorectal cancer is the fourth most common cancer worldwide and the second leading cause of cancer-related death. FOLFOX is the most common regimen used in the first-line chemotherapy in advanced colorectal cancer, but only half of the patients respond to this regimen and we have almost no clue in predicting resistance in such first-line application. Methods: To explore the potential molecular biomarkers predicting the resistance of FOLFOX regimen as the first-line treatment in advanced colorectal cancer, we screened microRNAs in serum samples from drug-responsive and drug-resistant patients by microarrays. Then differential microRNA expression was further validated in an independent population by reverse transcription and quantitative realtime PCR. Results: 62 microRNAs expressing differentially with fold-change >2 were screened out by microarray analysis. Among them, 5 (miR-221, miR-222, miR-122, miR-19a, miR-144) were chosen for further validation in an independent population (N=72). Our results indicated serum miR-19a to be significantly up-regulated in resistance-phase serum (p=0.009). The ROC curve analysis showed that the sensitivity of serum miR-19a to discriminate the resistant patients from the response ones was 66.7%, and the specificity was 63.9% when the AUC was 0.679. We additionally observed serum miR-19a had a complementary value for cancer embryonic antigen (CEA). Stratified analysis further revealed that serum miR-19a predicted both intrinsic and acquired drug resistance. Conclusions: Our findings confirmed aberrant expression of serum miR-19a in FOLFOX chemotherapy resistance patients, suggesting serum miR-19a could be a potential molecular biomarker for predicting and monitoring resistance to first-line FOLFOX chemotherapy regimens in advanced colorectal cancer patients.

Serum IL-33 as a diagnostic and prognostic marker in non- small cell lung cancer.

Abstract: Background: Interleukin-33 (IL-33) has recently been implicated in tumor immunity. The aim of this study was to explore the clinical role of serum IL-33 in patients with non-small-cell lung cancer (NSCLC). Methods: Sera collected from 250 healthy volunteers (HV), 256 patients with benign lung diseases (BLD) and 262 NSCLC cases were subjected to IL-33 ELISA and relationships between serum IL-33 and clinical characteristics were evaluated. Results: Circulating IL-33 levels were higher in the NSCLC group in comparison with the HV and BLD groups (p<0.001). Using a cut-off level 68 pg/ml (95% specificity in the HV group), IL-33 showed a good diagnostic performance for NSCLC. Multivariate survival analysis indicated that serum IL-33 was an independent prognostic factor in the entire NSCLC group [hazards ratio (HR) = 0.64 for low versus high IL-33 levels, 95% confidence interval (CI) 0.50–0.82; p<0.001] and in 165 selected patients with locally advanced or metastatic disease receiving chemoradiotherapy or chemotherapy (HR 0.70, 95% CI 0.52–0.94; p=0.013). Conclusions: IL-33 is a promising potential diagnostic and prognostic marker in NSCLC, independent of the therapeutic intervention.

Effects of the Hippo Signaling Pathway in Human Gastric Cancer

Abstract: Background/Aim: The Hippo signaling pathway is a newly discovered and conserved signaling cascade, which regulates organ size control by governing cell proliferation and apoptosis. This study aimed to investigate its effects in human gastric cancer. Methods: Tumor tissues (n=60), adjacent non-tumor tissues (n=60) and normal tissues (n=60) were obtained from the same patients with primary gastric cancer (GC). In addition, 70 samples of chronic atrophic gastritis (CAG) tissues were obtained from patients with intestinal metaplasia (IM) by endoscopic biopsy. Hippo signaling molecules, including Mst1, Lats1, YAP1, TAZ, TEAD1, Oct4 and CDX2, were determined by quantitative polymerase chain reaction (qPCR). Protein expression of Mst1, Lats1, YAP1, TEAD1 and CDX2 was assessed by immunohistochemistry and Western blotting. Results: Mst1, Lats1 and Oct4 mRNA expression showed an increasing tendency from GC tissues to normal gastric tissues, while the mRNA expression of YAP1, TAZ and TEAD1 was up-regulated (all P<0.01). Mst1 and Lats1 protein expression presented a similar trend with their mRNA expression. In addition, YAP1 and TEAD1 protein expression in GC was significantly higher than in the other groups (all P<0.01). CDX2 mRNA and protein expression in the CAG group were higher than in the other groups (all P<0.01). In GC, mRNA expression of Mst1, Lats1, Oct4, YAP1, TAZ, TEAD1 and CDX2 had a close correlation with lymphatic metastasis and tumor TNM stage (all P<0.01). Furthermore, protein expression of Mst1, Lats1 ,YAP1, TAZ, TEAD1 and CDX2 had a close correlation between each other (P<0.05). Conclusion: The Hippo signaling pathway is involved in the development, progression and metastasis of human gastric cancer. Therefore, manipulation of Hippo signaling molecules may be a potential therapeutic strategy for gastric cancer.

Epidemiology of primary CNS tumors in Iran: a systematic review

Abstract: Background: Although primary malignant CNS tumors are registered in the national cancer registry (NCR) of Iran, there are no available data on the incidence of the primary malignant or benign CNS tumors and their common histopathologies in the country. This study analyzed the 10-year data of the Iranian NCR from March 21, 2000 to March 20, 2010, including a systematic review. Materials and Methods: The international and national scientific databases were searched using the search keywords CNS, tumor, malignancy, brain, spine, neoplasm and Iran. Results: Of the 1,086 primary results, 9 papers were selected and reviewed, along with analysis of 10-year NCR data. The results showed that primary malignant brain tumors have an overall incidence of 2.74 per 100,000 person-years. The analysis of the papers revealed a benign to malignant ratio of 1.07. The most common histopathologies are meningioma, astrocytoma, glioblastoma and ependymoma. These tumors are more common in men (M/F=1.48). Primary malignant spinal cord tumors constitute 7.1% of the primary malignant CNS tumors with incidence of 0.21/100,000. Conclusions: This study shows that CNS tumors in Iran are in compliance with the pattern of CNS tumors in developing countries. The NCR must include benign lesions to understand the definitive epidemiology of primary CNS tumors in Iran.

Post-diagnosis Soy Food Intake and Breast Cancer Survival: A Meta-analysis of Cohort Studies

Abstract: Background and Objectives: Data on associations between soy food intake after cancer diagnosis with breast cancer survival are conflicting, so we conducted this meta-analysis for more accurate evaluation. Methods: Comprehensive searches were conducted to find cohort studies of the relationship between soy food intake after cancer diagnosis and breast cancer survival. Data were analyzed with comprehensive meta-analysis software. Results: Five cohort studies (11,206 patients) were included. Pooling all comparisons, soy food intake after diagnosis was associated with reduced mortality (HR 0.85, 95%CI 0.77 0.93) and recurrence (HR 0.79, 95%CI 0.72 0.87). Pooling the comparisons of highest vs. lowest dose, soy food intake after diagnosis was again associated with reduced mortality (HR 0.84, 95%CI 0.71 0.99) and recurrence (HR 0.74, 95%CI 0.64 0.85). Subgroup analysis of ER status showed that soy food intake was associated with reduced mortality in both ER negative (highest vs. lowest: HR 0.75, 95%CI 0.64 0.88) and ER positive patients (highest vs. lowest: HR 0.72, 95%CI 0.61 0.84), and both premenopausal (highest vs. lowest: HR 0.78, 95%CI 0.69 0.88) and postmenopausal patients (highest vs. lowest: HR 0.81, 95%CI 0.73 0.91). In additioin, soy food intake was associated with reduced recurrence in ER negative (highest vs. lowest: HR 0.64, 95%CI 0.44 0.94) and ER+/PR+ (highest vs. lowest: HR 0.65, 95%CI 0.49 0.86), and postmenopausal patients (highest vs. lowest: HR 0.67, 95%CI 0.56 0.80). Conclusion: Our metaanalysis showed that soy food intake might be associated with better survival, especially for ER negative, ER+/ PR+, and postmenopausal patients.

Projection of cancer incident cases for India -till 2026.

Abstract: Projection of cancer incidence is essential for planning cancer control actions, health care and allocation of resources. Here we project the cancer burden at the National and State level to understand the magnitude of cancer problem for the various calendar years from 2011 to 2026 at 5-yearly intervals. The age, sex and site-wise cancer incidence data along with populations covered by the registries were obtained from the report of National Cancer Registry Programme published by Indian Council of Medical Research for the period 2001-2004. Pooled age sex specific cancer incidence rates were obtained by taking weighted averages of these seventeen registries with respective registry populations as weights. The pooled incidence rates were assumed to represent the country’s incidence rates. Populations of the country according to age and sex exposed to the risk of development of cancer in different calendar years were obtained from the report of Registrar General of India providing population projections for the country for the years from 2001 to 2026. Population forecasts were combined with the pooled incidence rates to estimate the projected number of cancer cases by age, sex and site of cancer at various 5-yearly periods Viz. 2011, 2016, 2021 and 2026. The projections were carried out for the various leading sites as well as for ‘all sites’ of cancer. In India, in 2011, nearly 1,193,000 new cancer cases were estimated; a higher load among females (603,500) than males (589,800) was noted. It is estimated that the total number of new cases in males will increased from 0.589 million in 2011 to 0.934 million by the year 2026. In females the new cases of cancer increased from 0.603 to 0.935 million. Three top most occurring cancers namely those of tobacco related cancers in both sexes, breast and cervical cancers in women account for over 50 to 60 percent of all cancers. When adjustments for increasing tobacco habits and increasing trends in many cancers are made, the estimates may further increase. The leading sites of cancers in males are lung, oesophagus, larynx, mouth, tongue and in females breast and cervix uteri. The main factors contributing to high burden of cancer over the years are increase in the population size as well as increase in proportion of elderly population, urbanization, and globalization. The cancer incidence results show an urgent need for strengthening and augmenting the existing diagnostic/treatment facilities, which are inadequate even to tackle the present load.

Oleuropein induces apoptosis via the p53 pathway in breast cancer cells.

Abstract: Background: Breast cancer is a major health problem worldwide. Olive oil induces apoptosis in some cancer cells due to phenolic compounds like oleuropein. Although oleuropein has anticancer activity, the underlying mechanisms of action remain unknown. The study aimed to assess the mechanism of oleuropin-induced breast cancer cell apoptosis. Materials and Methods: p53, Bcl-2 and Bax gene expression was evaluated by semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR) in luminal MCF-7 cells. Results: Oleuropein-induced apoptosis was accompanied by up-regulation of both p53 and Bax gene expression levels and down-regulation in Bcl2. Conclusions: Oleuropein induces apoptosis in breast tumour cells via a p53-dependent pathway mediated by Bax and Bcl2 genes. Therefore, oleuropein may have therapeutic potential in breast cancer patients by inducing apoptosis via activation of the p53 pathway.

PAMAM dendrimers augment inhibitory effects of curcumin on cancer cell proliferation: possible inhibition of telomerase.

Abstract: Background: Despite numerous useful anticancer properties of curcumin, its utility is limited due to its hydrophobic structure. In this study, we investigated the comparative antiproliferative effect of PAMAM encapsulating curcumin with naked curcumin on the T47D breast cancer cell line. Materials and Methods: Cytotoxic effects of PAMAM dendrimers encapsulating curcumin and curcumin alone were investigated by MTT assay. After treating cells with different concentrations of both curcumin alone and curcumin encapsulated for 24h, telomerase activity was determined by TRAP assay. Results: While PAMAM dendrimers encapsulating curcumin had no cytotoxicity on cancer cells, they decreased the IC 50 for proliferation and also increased the inhibitory effect on telomerase activity. Conclusions: Considering the non-toxicity in addition to effectiveness for enhancing curcumin anticancer properties, dendrimers could be considered good therapeutic vehicles for this hydrophobic agent.

LKB1/AMPK/mTOR Signaling Pathway in Non-small-cell Lung Cancer

Abstract: Links between cancer and metabolism have been suggested for a long time but compelling evidence for this hypothesis came from the recent molecular characterization of the LKB1/AMPK signaling pathway as a tumor suppressor axis Besides the discovery of somatic mutations in the LKB1 gene in certain type of cancers, a critical emerging point was that the LKB1/AMPK axis remains generally functional and could be stimulated by pharmacological molecules such as metformin in cancer cells In addition, AMPK plays a central role in the control of cell growth, proliferation and autophagy through the regulation of mTOR activity, which is consistently deregulated in cancer cells Targeting of AMPK/mTOR is thus an attractive strategy in the development of therapeutic agents against non-small-cell lung cancer (NSCLC) In this review, the LKB1/AMPK/mTOR signaling pathway is described, highlighting its protective role, and opportunities for therapeutic intervention, and clinical trials in NSCLC

Nrf2 overexpression predicts prognosis and 5-FU resistance in gastric cancer

Abstract: Objective: NF-E2-related factor 2 (Nrf2) is activated in several human malignancies. However, the role of Nrf2 in gastric cancer (GC) remains incompletely understood. In this study, we therefore analyzed associations of Nrf2 expression status with clinical features and chemotherapeutic resistance in GC. Materials and Methods: A total of 186 samples from GC patients who underwent gastrectomy were used for prognostic assessment. A further 142 samples from GC cases who received first-line combination chemotherapy were applied for investigation of chemoresistance. The Nrf2 expression was evaluated by immunohistochemistry in GC samples, and its relationship with clinicopathological parameters and chemotherapy sensitivity was analyzed. The effect of Nrf2 gene silencing on chemotherapy resistance was also examined by cell viability assay in vivo. Results: Of the 186 patients with GC, 104/186 (55.9%) showed high expression for Nrf2. The overexpression of Nrf2 was an independent predictor of overall survival [OS, hazard ratio (HR) 3.9; P=0.011] and disease-free survival (DFS, HR 4.3; P=0.002). The gene silencing of Nrf2 reduced resistance to cell death induced by 5-FU in GC cell lines. Conclusion: Our data show that Nrf2 is an independent prognostic factor in GC. Furthermore, Nrf2 confers resistance to chemotherapeutic drug 5-FU in GC cells. Taken together, Nrf2 is a potential prognostic marker and predictive for 5-FU resistance in GC.

Clinico-pathological profile of lung cancer at AIIMS: a changing paradigm in India.

Abstract: Background: Lung cancer is one of the commonest and most lethal cancers throughout the world. The epidemiological and pathological profile varies among different ethnicities and geographical regions. At present adenocarcinoma is the commonest histological subtype of non-small cell lung cancer (NSCLC) in most of the Western and Asian countries. However, in India squamous cell carcinoma has been reported as the commonest histological type in most of the series. The aim of the study was to analyze the current clinico-pathological profile and survival of lung cancer at our centre. Materials and Methods: We analyzed 434 pathologically confirmed lung cancer cases registered at our centre over a period of three years. They were evaluated for their clinical and pathological profiles, treatment received and outcome. The available histology slides were reviewed by an independent reviewer. Results: Median age was 55 years with a male:female ratio of 4.6:1. Some 68% of patients were smokers. There were 85.3% NSCLC and 14.7% SCLC cases. Among NSCLCs, adenocarcinoma was the commonest histological subtype after the pathology review. Among NSCLC, 56.8% cases were of stage IV while among SCLC 71.8% cases had extensive stage disease. Some 29% of patients did not receive any anticancer treatment. The median overall and progression free survivals of the patients who received treatment were 12.8 and 7.8 months for NSCLC and 9.1 and 6.8 months for SCLC. Conclusions: This analysis suggests that adenocarcinoma may now be the commonest histological subtype also in India, provided a careful pathological review is done. Most of the patients present at advanced stage and outcome remains poor.

Identification of serum microRNA-21 as a biomarker for early detection and prognosis in human epithelial ovarian cancer.

Abstract: Recent investigations have confirmed up-regulation of serum miR-21 and its diagnostic and prognostic value in several human malignancies. In this study, we examined serum miR-21 levels in epithelial ovarian cancer (EOC) patients, and explored its association with clinicopathological factors and prognosis. The results showed significantly higher serum miR-21 levels in EOC patients than in healthy controls. In addition, increased serum miR-21 expression was correlated with advanced FIGO stage, high tumor grade, and shortened overall survival. These findings indicate that serum miR-21 may serve as a novel diagnostic and prognostic marker, and be used as a therapeutic target for the treatment of EOC.

Survival rate of breast cancer patients in Malaysia: a population-based study.

Abstract: Breast cancer is the most common cancer among Malaysian women. Other than hospital-based results, there are no documented population-based survival rates of Malaysian women for breast cancers. This population- based retrospective cohort study was therefore conducted. Data were obtained from Health Informatics Centre, Ministry of Health Malaysia, National Cancer Registry and National Registration Department for the period from 1st Jan 2000 to 31st December 2005. Cases were captured by ICD-10 and linked to death certificates to identify the status. Only complete data were analysed. Survival time was calculated from the estimated date of diagnosis to the date of death or date of loss to follow-up. Observed survival rates were estimated by Kaplan- Meier method using SPSS Statistical Software version 17. A total of 10,230 complete data sets were analysed. The mean age at diagnosis was 50.6 years old. The overall 5-year survival rate was 49% with median survival time of 68.1 months. Indian women had a higher survival rate of 54% compared to Chinese women (49%) and Malays (45%). The overall 5-year survival rate of breast cancer patient among Malaysian women was still low for the cohort of 2000 to 2005 as compared to survival rates in developed nations. Therefore, it is necessary to enhance the strategies for early detection and intervention.

Alcohol consumption and risk of cancer: a systematic literature review.

Abstract: This study aimed to discuss the consumption of alcohol as a risk factor for major cancers. We performed a search in the PubMed database, using the following inclusion criteria: meta-analysis published in English in the last 10 years that addressed the relationship between alcohol and the risk of developing cancer. The results indicate that moderate to heavy consumption of alcohol increases the risk of developing cancer of the oral cavity and pharynx, esophagus, stomach, larynx, colorectum, central nervous system, pancreas, breast and prostate. This review did not find any association between alcohol consumption and an increased risk of cancers of the lung, bladder, endometrium and ovary. It was also observed that alcohol consumption may be inversely related to thyroid cancer. Our systematic review has confirmed consumption of alcohol as a risk factor for the development of several types of cancer.