Cystitis and proctitis are defined as inflammation of bladder and rectum respectively. Haemorrhagic cystitis is the most severe clinical manifestation of radiation and chemical cystitis. Radiation proctitis and cystitis are major complications following radiotherapy. Prevention of radiation-induced haemorrhagic cystitis has been investigated using various oral agents with minimal benefit. Bladder irrigation remains the most frequently adopted modality followed by intra-vesical instillation of alum or formalin. In intractable cases, surgical intervention is required in the form of diversion ureterostomy or cystectomy. Proctitis is more common in even low dose ranges but is self-limiting and improves on treatment interruption. However, treatment of radiation proctitis is broadly non-invasive or invasive. Non-invasive treatment consists of non-steroid anti-inflammatory drugs (NSAIDs), anti-oxidants, sucralfate, short chain fatty acids and hyperbaric oxygen. Invasive treatment consists of ablative procedures like formalin application, endoscopic YAG laser coagulation or argon plasma coagulation and surgery as a last resort.

Electrical impedance tomography (EIT) is a new non-invasive, mobile screening method which does not use ionizing radiation to the human breast. It is based on the theory that cancer cells display altered local dielectric properties, thus demonstrating measurably higher conductivity values. This article reviews the utilisation of EIT in breast cancer detection. It could be used as an adjunct to mammography and ultrasonography for breast cancer screening.

In oncology various imaging modalities play a crucial role in diagnosis, staging, restaging, treatment monitoring and follow up of various cancers. Stand-alone morphological imaging like computerized tomography (CT) and magnetic resonance imaging (MRI) provide a high magnitude of anatomical details about the tumor but are relatively dumb about tumor physiology. Stand-alone functional imaging like positron emission tomography (PET) and single photon emission tomography (SPECT) are rich in functional information but provide little insight into tumor morphology. Introduction of first hybrid modality PET/CT is the one of the most successful stories of current century which has revolutionized patient care in oncology due to its high diagnostic accuracy. Spurred on by this success, more hybrid imaging modalities like SPECT/CT and PET/MR were introduced. It is the time to explore the potential applications of the existing hybrid modalities, developing and implementing standardized imaging protocols and train users in nuclear medicine and radiology. In this review we discuss three existing hybrid modalities with emphasis on their technical aspects and clinical applications in oncology.

Thousands of people die each year from cancer due to occupational causes. To reduce cancer in workers, preventive strategies should be used in the high-risk workplace. The effective prevention of occupational cancer requires knowledge of carcinogen agents. Like other areas of healthcare industry, occupational health has been affected by information technology solutions to improve prevention, early detection, treatment and finally the efficiency and cost effectiveness of the healthcare system. Information technology solutions are thus an important issue in the healthcare field. Information about occupational cancer in information systems is important for policy makers, managers, physicians, patients and researchers; because examples that include high quality data about occupational cancer patients and occupational cancer causes are able to determine the worker groups which require special attention. As a result exposed workers who are vulnerable can undergo screening and be considered for preventive interventions.

Clinicians should looking for techniques that helps to early diagnosis of cancer, because early cancer detection is critical to increase survival and cost effectiveness of treatment, and as a result decrease mortality rate. Medical images are the most important tools to provide assistance. However, medical images have some limitations for optimal detection of some neoplasias, originating either from the imaging techniques themselves, or from human visual or intellectual capacity. Image processing techniques are allowing earlier detection of abnormalities and treatment monitoring. Because the time is a very important factor in cancer treatment, especially in cancers such as the lung and breast, imaging techniques are used to accelerate diagnosis more than with other cancers. In this paper, we outline experience in use of image processing techniques for lung and breast cancer diagnosis. Looking at the experience gained will help specialists to choose the appropriate technique for optimization of diagnosis through medical imaging.

Pancreatic cancer is a fatal malignancies which is predominantly seen in men and at advanced age (40-85 years) and has an aggressive course. Its frequency is gradually increasing over the past years. It accounts for 2% of all cancers and 5% of cancer-related deaths. Pancreatic cancer takes the first place among asymptomatic cancers. Ninety percent of cases are adenocarcinomas. Ten percent of the patients have a familial disposition. The disease is very difficult to detect as it has no early signs and spreads rapidly to surrounding organs is one of the most deadly types of cancer. Pancreatic cancer may result from hereditary germline or somatic acquired mutations in cancer-related genes and mutations also cause cancer progression and metastasis.

Background: ${\beta}$-catenin plays a crucial role in the progression of breast cancer (BC) and a prognostic role of in BC patients has been widely reported. However, controversy still remains. Materials and Methods: Identical search strategies were used to search relevant literature in electronic databases updated to July 1, 2014. Individual hazard ratios (HRs) and 95% confidence intervals (CIs) were extracted and pooled HRs with 95%CIs were used to evaluate the strength of association between positive ${\beta}$-catenin expression in different subcellular locations and survival results of BC patients. Subgroup and meta-regression analyses were performed to explore heterogeneity. Funnel plots of Begg's and Egger's linear regression test were used to investigate publication bias. Heterogeneity and sensitivity were also assessed. All the work was completed using STATA. Results: A total of 2,204 patients from 12 evaluative studies were finally included. Pooled HRs and 95%CIs suggested that ${\beta}$-catenin expression in cytoplasm/nucleus had an unfavorable impact on both overall survival (OS) (HR: 1.93, 95%CI: 1.40-2.65) and disease free survival (DFS)/ recurrent free survival (RFS) (HR: 1.60, 95%CI: 1.20-2.13) in BC patients. However, here was no significant association between ${\beta}$-catenin expression in the membranes with OS (HR: 0.65, 95%CI: 0.42-1.02) or DFS/RFS (HR: 0.66, 95%CI: 0.38-1.13). Publication bias was absent in all of the four outcomes. Sensitivity analysis revealed that the results of this meta-analysis were robust. Conclusions: Positive ${\beta}$-catenin expression in cytoplasm/nucleus rather than in membrane is a significant prognostic factor in patients with BC who have been surgically treated.

Background: Cirrhosis is regarded as a possible end stage of many liver diseases, including viral infection. It occurs when healthy liver tissue becomes damaged and is replaced by scar tissue and finally may lead to hepatocellular carcinoma. Interferons (IFNs)are two general categories, type I and II. Type I includes one beta interferon and over 20 different alpha interferons. Alpha interferons are very similar in how they work, interacting with other proteins on cells like receptors. The main objective of this study was to compare Mx gene productivity post different cell line treatment with imported and Egyptian biosimilar locally produced IFNs, as well as the efficacy of those tested IFNs. Also, an assessment was made of sensitivity of different cell lines as alternatives to that recommended for evaluation of antiviral activity. Materials and Methods: Different cell lines (Vero, MDBK and Wish) were employed to evaluate cytotoxicity using the MTT assay. Antiviral activity was evaluated compared with standard IFN against VSV, Indiana strain -156, on tested rh-IFNs (imported; innovated and Egyptian biosimilar locally produced IFNs) in the pre-treated cell lines previously mentioned. The virus was propagated in the Wish cell line as recommended. Finally we estimated up-regulation of the Mx gene as a biomarker. Results: Data recorded revealed that test IFNs were safe in test cell lines. Viability was around 100%. Locally tested interferon did not realize the international potency limits, while the imported one was accepted compared with the standard IFN. These results were the same either using infectivity titer reduction assay or crystal violet staining of residual non- infected cells. Mx protein production was cell type related and confirmed by the detected Mx gene expressed in imported and locally produced IFN pre-treated cell lines. The expression of the gene was arranged in the order of Vero> wish > MDBK for the imported IFN, while for the Egyptian biosimillar locally produced one it was MDBK> Vero> wish. With regard to the antiviral activity there was a significant difference of imported IFN potency compared with the locally produced IFN (P<0.05), the IFN potential (antiviral activity) was not cell line related and showed non-significant difference for each separate product. Conclusions: Vero cells can be used as an alternative cell line for evaluation of IFN potency in case of unavailable USP recommended cell lines. Alternative potency evaluation assay could be used and proved significant difference in IFN potency in case of local and imported agents. Evaluation of antiviral activity could be used in parallel to viral infectivity reduction assay for better accuracy. Mx gene can be used as a marker for IFN potential.

Background: The aim was to see compliance to minimum data set information in carcinoma cervix histopathology reports from a team of 13 pathologists; and also to analyse the distribution of parameters like tumor size, grade, depth of cervical stromal invasion, lymph node yield and pTNM stage. Materials and Methods: All pathology reports of radical hysterectomy for carcinoma cervix operated in house within a three year duration (2010-2012), (n=204) were retrieved from medical records and analyzed for the above parameters. Results: In 2010- 59 cases, in 2011- 67 cases and in 2012- 78 cases of carcinoma cervix underwent operations in our hospital. The median age was 50.5 years and the maximum T diameter was 2.8 cms in the reports of three years. Squamous carcinoma was the commonest subtype amongst all the tumors. It was noted that 60.8% of cases had cervical stromal involvement more than half the thickness of the cervical stroma. Parametrial involvement was seen in 4.82% of cases. pTNM Staging was not mentioned in 65.06% of the cases. The mean bilateral pelvic lymph node yield count in our study was 16.6 inclusive of all the three years. Conclusions: Compliance with provision of a minimum dataset in our team of 13 pathologists was generally good. Lymph node yield in our hands is reasonable, but constant striving for greater numbers should be made. pTNM staging should be more meticulously documented. Use of proformas /checklists is recommended.

Gall bladder cancer (GBC) is a gastro-intestinal cancer with high prevalence among north Indian women. Platelet derived growth factor-B (PDGFB) and human epidermal growth factor receptor-2 (HER2) may play roles in the etiology of GBC through the inflammation-hyperplasia-dysplasia-carcinoma pathway. To study the association of PDGFB and HER2 polymorphisms with risk of GBC, 200 cases and 300 controls were considered. PDGFB +286A>G and +1135A>C polymorphisms were investigated with an amplification refractory mutation system and the HER2 $Ile^{655}Val$ polymorphism by restriction fragment length polymorphism. Significant risk associations for PDGFB +286 GG (OR=5.25) and PDGFB +1135 CC (OR=3.19) genotypes were observed for GBC. Gender wise stratification revealed susceptibility for recessive models of PDGFB +1135A>C (OR=3.00) and HER2 $Ile^{655}Val$ (OR=2.52) polymorphisms among female GBC cases. GBC cases with gall stones were predisposed to homozygous +286 GG and +1135 CC genotypes. Significant risk associations were found for ACIle (OR=1.48), GAVal (OR=1.70), GAIle (OR=2.00) haplotypes with GBC cases and GCIle haplotype with female GBC cases (OR=10.37, P=<0.0001). Pair-wise linkage disequilibrium revealed negative associations among variant alleles. On multi-dimensional reduction analysis, a three factor model revealed significant gene-gene interaction for PDGFB +286A>G, PDGFB +1135A>C and HER2 Ile165Val SNPs with GBC. Protein-protein interaction showed significant association of PDGFB and HER2 with the epidermal growth factor receptor signaling pathway.

Purpose: To assess the role of two adjuvant chemotherapy regimens, anthracycline-based and CMF on disease free survival and overall survival breast cancer patients by meta-analysis approach in Eastern Mediterranean and Asian countries to determine which is more effective and evaluate the appropriateness and efficiency of two different proposed statistical models. Materials and Methods: Survival curves were digitized and the survival proportions and times were extracted and modeled to appropriate covariates by two multivariate mixed effects models. Studies which reported disease free survival and overall survival curves for anthracycline-based or CMF as adjuvant chemotherapy that were published in English in the Eastern Mediterranean region and Asia were included in this systematic review. The two transformations of survival probabilities (Ln (-Ln(S)) and Ln(S/ (1-S))) as dependent variables were modeled by a multivariate mixed model to same covariates in order to have precise estimations with high power and appropriate interpretation of covariate effects. The analysis was carried out with SAS Proc MIXED and STATA software. Results: A total of 32 studies from the published literature were analysed, covering 4,092 patients who received anthracycline-based and 2,501 treated with CMF for the disease free survival and in order to analyze the overall survival, 13 studies reported the overall survival curves in which 2,050 cases were treated with anthracycline-based and 1,282 with CMF regimens. Conclusions: The findings illustrated that the model with dependent variable Ln (-Ln(S)) had more precise estimations of the covariate effects and showed significant difference between the effects of two adjuvant chemotherapy regimens. Anthracycline-based treatment gave better disease free survival and overall survival. As an IPD meta-analysis in the Italy the results of Angelo et al in 2011 also confirmed that anthracycline-based regimens were more effective for survival of breast cancer patients. The findings of Zare et al 2012 on disease free survival curves in Asia also provided similar evidence.

Background: Earlier studies on the association between p53 codon 72 Arg>Pro polymorphism and cancer risk were inconclusive and conflicting for the Saudi population. Therefore, we performed a meta-analysis to investigate the relationship between the codon 72 Arg>Pro polymorphism and overall cancer risk in Saudi Arabia. Materials and Methods: We searched all eligible published studies and data were pooled together to perform the meta-analysis. Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated for homozygous, heterozygous, dominant and recessive genetic models. Results: A total of five eligible published studies covering 502 cancer cases and 784 healthy controls were included in the meta-analysis. No publication bias was detected in this study. The results suggested that the variant (Pro vs Arg: p=0.960; OR=1.004, 95% CI=0.852-1.183), homozygous (Pro.Pro vs Arg.Arg: p=0.970; OR=1.006, 95% CI=0.729-1.390), heterozygous (Arg.Pro vs Arg.Arg: p=0.473; OR=0.783, 95% CI=0.402-1.527) carriers were not associated with overall cancer risk. Similarly, dominant (Pro.Pro+Pro.Arg vs Arg.Arg: p=0.632; OR=0.886, 95% CI=0.540-1.454) and recessive (Pro.Pro vs Pro.Arg+Arg.Arg: p=0.269; OR=1.163, 95%CI=0.890-1.521) models also did not indicate increased risk of cancer. Conclusions: The current meta-analysis suggests that the codon 72 Arg>Pro polymorphism of the p53 gene might not contribute to cancer susceptibility in Saudi population. Future well designed large case control studies are needed to validate our findings.

Background: Breast cancer is the most prevalent kind of cancer among women in Iran. Regarding the importance of cancer prevention and considerable variation of breast cancer incidence in different parts of the country, it is necessary to recognize regions with high incidence of breast cancer and evaluate the role of potential risk factors by use of advanced statistical models. The present study focussed on incidence of breast cancer in Iran at the province level and also explored the impact of some prominent covariates using Bayesian models. Materials and Methods: All patients diagnosed with breast cancer in Iran from 2005 to 2008 were included in the study. Smoking, fruit and vegetable intake, physical activity, obesity and the Human Development Index (HDI), measured at the province level, were considered as potential modulating factors. Gamma-Poisson, log normal and BYM models were used to estimate the relative risk of breast cancer in this ecological investigation with and without adjustment for the covariates. Results: The unadjusted BYM model had the best fit among applied models. Without adjustment, Isfahan, Yazd, and Tehran had the highest incidences and Sistan- Baluchestan and Chaharmahal-Bakhtiari had the lowest. With the adjusted model, Khorasan-Razavi, Lorestan and Hamedan had the highest and Ardebil and Kohgiluyeh-Boyerahmad the lowest incidences. A significantly direct association was found between breast cancer incidence and HDI. Conclusions: BYM model has better fit, because it contains parameters that allow including effects from neighbors. Since HDI is a significant variable, it is also recommended that HDI should be considered in future investigations. This study showed that Yazd, Isfahan and Tehran provinces feature the highest crude incidences of breast cancer.

Background: Low-risk human papillomavirus (LR-HPV) infection is the main cause of genital warts. LRHPV genotypes 6 and 11 are associated with genital warts, but there have only been a few published studies about the genotype-specific prevalence of HPV in genital warts in China. The objective of our study was to assess the prevalence of HPV genotypes for clinical cases involving both men and women and to evaluate the potential benefit of a quadrivalent (genotypes 6, 11, 16, and 18) HPV vaccine in eastern Guangdong province of China. Materials and Methods: A total of 696 eligible patients with genital warts were enrolled during the period Aug 2009 through Oct 2014. Specimens were collected from genital warts, the HPV GenoArray test was used for HPV detection and genotyping, which could detect 21 HPV genotypes, including genotypes 6, 11, 16, and 18. Results: Among the 696 cases, 675 samples were successfully genotyped. The median age of patients was 32.1 years (range, 16-67 years). The most prevalent genotypes were HPV-6 (285/675, 42.2%), HPV-11 (265/675, 39.3%), HPV-52 (52/675, 7.7%), HPV-16 (51/675, 7.56%), HPV-81 (50/675, 7.40%) and HPV-58 (37/675, 5.48%). Low-risk genotypes predominated, with a prevalence of 96.59%. The cumulative prevalence of genotypes 6 and 11 was 78.7% (531/675), the cumulative prevalence of genotypes 16 and 18 was 11.6% (78/675), and the cumulative prevalence of genotypes 6, 11, 16, and 18 was 82.5% (557/675). Conclusions: Our results provide strong evidence that, in eastern Guangdong, different from Western countries, the most prevalent low risk HPV genotypes in patients with genital warts are 6, 11 and 81. The quadrivalent HPV vaccine could prevent 82.5% of genital warts in eastern Guangdong.

Background: Pancreatic cancer ranks fourth in deaths caused by cancers throughout the world. Gemcitabine chemotherapy is the primary method of treatment of advanced pancreatic cancer, and in asco2014, it is still firstline chemotherapy. Howeve,r gemcitabine+fluorouracil regimens are also licensed and widely used worldwide. Clinical trials are the best way to evaluate drug efficacy. In this study, we performed a systematic review and a meta-analysis of randomized controlled trials (RCTs) to assess whether gemcitabine+fluoropyrimidine combination therapy improves the prognosis of unresectable pancreatic cancer compared with gemcitabine treatment alone. Materials and Methods: A quantitative up-to-date meta-analysis was undertaken to investigate the efficacy of gemcitabine-based combination treatment compared with gemcitabine monotherapy for locally advanced or metastatic pancreatic cancer. Inclusion was limited to high-quality randomized clinical trials. Results: A total of 12 studies were included in the present analysis, with a total of 3,038 patients recruited. The studies were divided into three subgroups including 5-FU / CAP / S-1 combined with gemcitabine. For the primary endpoint of overall survival (OS), gemcitabine-based combination therapy demonstrated significantly better outcome (HR, 0.88; 95% CI, 0.81-0.95) than gemcitabine monotherapy. The analysis of progression free survival (PFS) also provided a significant result for the combined therapy in a total of 8 trials (2,130 patients) (HR, 0.74; 95% CI, 0.63-0.86). With subgroup analysis according to the method of dosing delivery, we found that in the injection group with 3 trials (889 patients), a negative result was found (HR, 0.93; 95% CI, 0.77-1.12); while a positive result was observed in the oral group with 9 trials (2,149 patients) (HR, 0.87; 95% CI, 0.80-0.95). Conclusions: Gemcitabine combination therapy provides a modest improvement of survival, but is associated with more toxicity compared with gemcitabine monotherapy.

Background: Factors predictive of survival have been identified in Western patients with metastatic clear cell renal cell carcinoma (mCCRCC) treated with sunitinib. Less is known, however, about factors predictive of survival in Japanese patients. This study evaluated factors prognostic of survival in Japanese patients with mCCRCC treated with first-line sunitinib. Materials and Methods: This retrospective study evaluated 46 consecutive Japanese mCCRCC patients treated with sunitinib as first line therapy. Clinical and biochemical markers associated with progression-free survival (PFS) were analyzed, with prognostic factors selected by uniand multivariate Cox regression analyses. Results: Univariate analysis showed that factors significantly associated with poor PFS included Memorial Sloan-Kettering Cancer Center poor risk scores, International Metastatic RCC Database Consortium poor risk and high (>0.5 mg/dl) serum C-reactive protein (CRP) concentrations (p<0.001 each). Multivariate analysis showed that high serum CRP was independently associated with poorer PFS (p=0.040). Six month disease control rate (complete response, partial response and stable disease) in response to sunitinib was significantly higher in patients with normal (${\leq}0.5mg/dl$) than elevated baseline CRP (p<0.001). Conclusions: CRP is a significant independent predictor of PFS for Japanese patients with mCCRCC treated with first-line sunitinib. Pretreatment CRP concentration may be a useful biomarker predicting response to sunitinib treatment.

Background: Continuous surveillance of pattern of blood stream infection is necessary in febrile neutropenia (FN)especially with the recent escalating trend in the management of pediatric cancer patients towards intensified regimens and with the increase in infections caused by resistant organisms limiting the choice of antibiotics. Aim: To monitor change in pattern of blood stream infections (BSI) in FN pediatric cancer patients. Materials and Methods: Surveillance of FN episodes with positive BSI was prospectively monitored and compared to a previous surveillance in the same pediatric oncology unit. Results: A total of 232 BSI positive episodes were documented in 192 patients during a 6 months period. The results of recent surveillance analysis showed an increase in intensified regimens of chemotherapy, antimicrobial resistance, fungal infections, and prolonged duration of episodes when compared to previous surveillance, with p value sof <0.001, 0.005, 0.021, and <0.001, respectively. There was an apparent decrease in the crude mortality but this was not statistically significant, to 6% in 2011 from 10 % in 2006. Conclusions: The pattern of BSI at our institution is still inclining towards gram positive organisms but is showing a shift towards more antibiotic resistance and fungal infections.

Background: Medicinal plants, especially examples rich in polyphenolic compounds, have been suggested to be chemopreventive on account of antioxidative properties. Punica granatum (PG) (pomegranate) is a well known fruit in this context, but its cytotoxicity in cancer cells has not been extensively studied. Here, we investigated the antiproliferative properties of a peel extract of PG from Iran in different human cancer cells. Materials and Methods: A methanolic extract of pomegranate peel (PPE) was prepared. Total phenolic content(TPC) and total flavonoid conetnt (TFC) were determined by colorimetric assays. Antioxidant activity was determined by DPPH radical scavenging activity. The cytotoxicity of different doses of PPE (0, 5, 20, 100, 250, 500, $1000{\mu}g/ml$) was evaluated by MTT assays with A549 (lung non small cell cancer), MCF-7 (breast adenocarcinoma), SKOV3 (ovarian cancer), and PC-3 (prostate adenocarcinoma) cells. Results: Significant (P<0.01) or very significant (P<0.0001) differences were observed in comparison with negative controls at all tested doses (5-$1000{\mu}g/ml$). In all studied cancer cells, PPE reduced the cell viability to values below 40%, even at the lowest doses. In all cases, IC50 was determined at doses below $5{\mu}g/ml$. In this regard, MCF-7 breast adenocarcinoma cells were the most responsive cells to antiprolifreative effects of PPE with a maximum mean growth inhibition of 81.0% vs. 69.4%, 79.3% and 77.5% in SKOV3, PC-3 and A549 cells, respectively. Conclusions: Low doses of PPE exert potent anti-proliferative effects in different human cancer cells and it seems that MCF-7 breast adenocarcinoma cells are the most cells and SKOV3 ovarian cancer cells the least responsive in this regard. However, the mechanisms of action need to be addressed.

Background: Medicinal plants, especially examples rich in polyphenolic compounds, have been suggested to be chemopreventive on account of their antioxidative properties. Melissa officinalis L. (MO), an aromatic and medicinal plant, is well known in thios context. However, toxicity against cancer cells has not been fully studied. Here, we investigated the selective anticancer effects of an MO extract (MOE) in different human cancer cells. Materials and Methods: a hydro-alcoholic extract of MO was prepared and total phenolic content (TPC) and total flavonoid content (TFC) were determined by colorimetric assays. Antioxidant activity was determined by DPPH radical scavenging activity. MTT assays were used to evaluate cytotoxicity of different doses of MOE (0, 5, 20, 100, 250, 500, $1000{\mu}g/ml$) towards A549 (lung non small cell cancer cells), MCF-7 (breast adenocarcinoma), SKOV3 (ovarian cancer cells), and PC-3 (prostate adenocarcinoma) cells. Results: Significant (P<0.01) or very significant (P<0.0001) differences were observed in comparison to negative controls at all tested doses ($5-1000{\mu}g/ml$). In all cancer cells, MOE reduced the cell viability to values below 33%, even at the lowest doses. In all cases, $IC_{50}$ values were below $5{\mu}g/ml$. The mean growth inhibition was 73.1%, 86.7%, 79.9% and 77.8% in SKOV3, MCF-7 and PC-3 and A549 cells, respectively. Conclusions: Our results indicate that a hydro-alcoholic extract of MO possess a high potency to inhibit proliferation of different tumor cells in a dose independent manner, suggesting that an optimal biological dose is more important than a maximally tolerated one. Moreover, the antiprolifreative effect of MO seems to be tumor type specific, as hormone dependant cancers were more sensitive to antitumoral effects of MOE.

Aim: To assess the treatment outcome in patients with malignant skin melanoma and prognostic factors for distant metastases (DM), disease-free survival (DFS) and overall survival (OS). Materials and Methods: A retrospective analysis was conducted on 113 patients with malignant skin melanoma (60 females, 53 males, average age-55 years) who were treated surgically. Primary treatment consisted of local excision. In 12 cases, it was accompanied by lymph node excision. In 93 (82%) cases, radicalization was necessary, which was either local only (19 cases) or accompanied by lymph node surgery/biopsy (74 cases). Possible prognostic factors such as Clark's stage and Breslow's depth of invasion, ulceration, average tumor dimensions, lymph nodes metastases (pN+), gender, tumor location and primary excision margins were considered. Results: In 51 (45%) cases, treatment failure occurred. The 5-year DM rate was 47%, the 5-year DFS was 38%, and the 5-year OS was 56%. In the univariate analysis, the important factors with respect to at least one endpoint included Clark's stage, Breslow's depth of invasion, ulceration, average tumor dimensions, lymph nodes metastases, gender and primary tumor localization. The presence of metastasic nodes was the most important prognostic factor, with a 5-year DM rates of 30% for pN(-) and 76% for pN(+) and a 5-year DFS and OS of 56% and 76% for pN(-) and 13% and 24% for pN(+), respectively. The average tumor dimension was independently significant for DFS and OS, with 5-year rates of 69% and 80% for ${\leq}1cm$, 28% and 53% for 1-2 cm, and 18% and 30% for >2 cm, respectively. Tumor location was also significant for DM and OS, with 5-year rates of 69% vs 33% and 41% vs 66% for trunk vs other locations, respectively. Conclusions: The natural course of a malignant skin melanoma treated radically is disadvantageous, with unsuccessful outcome in nearly half of the cases. Common clinical factors, such as Clark's tumor stage, Breslow's depth of invasion and the presence of metastatic nodes, have high prognostic significance. The size and location of the primary lesion may be considered independent prognostic factors. The most important negative prognostic factor is the presence of metastatic regional lymph nodes. Only one quarter of patients with metastases in lymph nodes survive 5 years from primary surgery.

Background: Breast cancer is the most common malignancy of women in the world. The disease is caused by infectious and non-infectious, environmental and lifestyle factors. Tobacco smoke has been one of the most widely studied environmental factors wiith possible relevance to breast cancer. The purpose of this study was to assess the impact of tobacco smoking in breast cancer patients in a hospital based cohort and to establish prognostic implications if any. Materials and Methods: A retrospective audit of 100 women with pathological diagnosis of invasive breast cancer was included in this study. The verbal questionnaire elicited information on current and previous history of exposure to smoking in addition to active smoking. All analyses were adjusted for potential confounders, including stage at presentation, alcohol intake, hormonal replacement therapy, oral contraceptive intake, obesity and menopausal status. Results: The mean age at presentation of breast cancer was $51.4{\pm}10.86$ years. Mean age of presentation was $53.1{\pm}11.5$ and $45.7{\pm}11.9$ years in never smokers and passive smokers, respectively. Age at presentation varied widely in patients exposed to tobacco smoke for >10 years in childhood from $40.3{\pm}12.0$ years to $47.7{\pm}13.9$ in patients exposed for > 20years as adults. Among passive smokers, 60.9% were premenopausal and 39.1% of patients were postmenopausal. In never smokers, 71.4% were post menopausal. Expression of receptors in non-smokers vs passive smokers was comparable with no significant differences. Metastatic potential in lung parenchyma was slightlyelevated in passive smokers as compared to never smokers although statistically non-significant. Conclusions: An inverse relationship exists between the intensity and duration of smoking and the age at presentation and poor prognostic factors. The results strongly suggest efforts should be taken to prevent smoking, encourage quitting and restrict exposure to second hand smoke in India.

Lung cancer is the leading contributor to cancer deaths in the developing world. Within countries, significant variability exists in the prevalence of lung cancer risk, yet limited information is available whether some of the observed variability is associated with differences in the consumption pattern of local tobacco products with differing potency. We recruited 606 lung cancer cases and 606 controls from the B.P. Koirala Memorial Cancer Hospital in Nepal from 2009-2012. We estimated odds ratios (ORs) and 95% confidence intervals (CI) for lung cancer risk associated with different tobacco products, using unconditional logistic regression. Unfiltered cigarettes tended to be the most frequently used products across ethnic subgroup with about 53.7% of Brahmins, 60.1% of Chettris, and 52.3% of Rai/Limbu/Magar/others. In contrast, about 39.9% of Madishe/Tharu smokers reported using bidi compared with only 27.7% who smoked unfiltered cigarettes. Among those who only smoked one type of product, choor/kankat smokers had the highest lung cancer risk (OR 10.2; 95% CI 6.2-16.6), followed by bidi smokers (OR 5.6; 95% CI 3.6-8.7), unfiltered cigarettes (OR 4.9; 95% CI 3.4-7.2), and filtered cigarettes (OR 3.4; 95% CI 2.2-5.3). A clear dose-response relationship was observed between increased frequency of smoking and lung cancer risk across all ethnic subgroups. These results highlight the important role of traditional tobacco products on lung cancer risk in the low income countries.

Background: There is a long standing interest in natural compounds especially those with a high polyphenolic content and high scavenging activity for hazardous free radicals. Cornus mas (CM) fruit is well known for its antioxidant activities; however, its toxicity against human cancers needs to be addressed. Here, we investigated selective anticancer effects of CM on different human cancer cells. Materials and Methods: A hydro-alcoholic extract of CM (HECM) was prepared and total phenolic content (TPC) and total flavonoid content (TFC) were determined by colorimetric assays. Antioxidant activity was assessed with respectto DPPH radical scavenging. MTT assays were used to evaluate the cytotoxicity of different doses of CM (0, 5, 20, 100, 250, 500, $1000{\mu}g/ml$) towards A549 (lung non small cell cancer), MCF-7 (breast adenocarcinoma), SKOV3 (ovarian cancer) and PC-3 (prostate adenocarcinoma) cells. Results: Significant (P<0.05) or very significant (P<0.001) differences were observed in comparison to negative controls at all tested doses ($5-1000{\mu}g/ml$). In all cancer cells, HECM reduced the cell viability to values below 26%, even at the lowest doses. In all cases, $IC_{50}$ was obtained at doses below $5{\mu}g/ml$. The mean growth inhibition was 81.8%, 81.9%, 81.6% and 79.3% in SKOV3, MCF-7, PC-3 and A549 cells, respectively. Conclusions: Altogether, to our best knowledge, this is a first study that evaluated toxicity of a HECM with high antioxidant activity in different human cancer cells in vitro. Our results indicated that a hydro-alcoholic extract of CM possesses high potency to inhibit proliferation of different tumor cells in a dose independent manner, suggesting that an optimal biological dose is more important and relevant than a maximally tolerated one.

The primary objective of this study was to assess the knowledge of medical students and determine variation between different cultural groups. A secondary aim was to find out the willingness to pay for cervical cancer vaccination and the relationships between knowledge and attitudes towards Human Papillomavirus vaccination. A cross-sectional survey was conducted in a private medical university between June 2014 and November 2014 using a convenient sampling method. A total of 305 respondents were recruited and interviewed with standard questionnaires for assessment of knowledge, attitudes and practice towards human papilloma virus and their willingness to pay for HPV vaccination. Knowledge regarding human papilloma virus, human papilloma virus vaccination, cervical cancer screening and cervical cancer risk factors was good. Across the sample, a majority (90%) of the pupils demonstrated a high degree of knowledge about cervical cancer and its vaccination. There were no significant differences between ethnicity and the participants' overall knowledge of HPV infection, Pap smear and cervical cancer vaccination. Some 88% of participants answered that HPV vaccine can prevent cervical cancer, while 81.5% of medical students said they would recommend HPV vaccination to the public although fewer expressed an intention to receive vaccination for themselves.

Purpose: To understand the epidemiology of different upper gastrointestinal (UGI) tract related abnormalities through endoscopic data analysis. Materials and Methods: A retrospective study of three years from January 2009 to December 2011 was conducted with data from endoscopic surveillance of upper GI tract problems, collected from the Gastroenterology Unit, Osmania General Hospital, Hyderabad. MS excel and Medcalc software (comparison of proportions) were used for data analysis. Results: A total of 10,029 (6,468 in males and 3,561 in females) endoscopies were performed during this three-year period. The male to female ratio was 1.8:1. Overall, ~30% of endoscopies evaluated showed patients with acid peptic disorders, 13.6% with vascular-related abnormalities, 10.6% showed structural abnormalities, followed by 6.3% with malignancies. Burden of malignancies was mostly observed in the older age group (60-69 years). Esophageal cancer cases decreased (p=0.0001) whereas stomach cancers increased over this period (p=0.0345). We also observed an increased incidence of acid peptic disease (APD) (p=0.0036) and gastroesophageal reflux disease (GERD) (p=0.0002) cases during this period. Conclusions: Endoscopic diagnosis is useful for early detection of UGI anomalies and helpful for physicians to manage and treat varied kinds of UGI disorders. Analysis of data revealed changing trends in the incidence of various pathologies of the UGI tract. Functional dyspepsia and GERD definitely reduce the quality of life of the individual. The role of our diverse dietary habits and lifestyle associated with these problems have not yet been established, though there have been reports on the effect of coffee, spicy food, wheat-based diet, screening of UGI pathologies along with collection of complete personal and medical history details, can h elp in correlating the patients' condition with various aspects of lifestyle and diet.

Cervical carcinoma is the main cause of cancer-related mortality in women and is correlated with more than 15 risk cofactors, including infection of cervical cells with high-risk types of HPV (hrHPV). Indeed, both aberrant methylation of the RASSF1A promoter and hrHPV infection are often observed in cervical carcinomas. The purpose of our meta-analysis was to evaluate the role of RASSF1A promoter methylation and hrHPV infection in cervical cancer. Our meta-analysis involved 895 cervical cancer patients and 454 control patients from 15 studies. Our results suggested that RASSF1A promoter hypermethylation increased the risk of cervical cancer (OR=9.77, 95%CI=[3.06, 31.26], P=0.0001, $I^2=78%$). By grouping cases according to cancer subtypes, we found that HPV infection was higher in cervical squamous cell carcinomas (SCCs) than in cervical adenocarcinomas/adenosquamous cancers (ACs/ASCs) (OR=4.00, 95%CI=[1.41, 11.30], P=0.009, $I^2=55%$). Interestingly, HPV infection tended to occur in cervical cancers with relatively low levels of RASSF1A promoter methylation (OR=0.59, 95%CI=[0.36, 0.99], P=0.05, I2=0%). Our study provides evidence of a possible interaction between HPV infection and RASSF1A promoter methylation in the development of cervical cancers.

Background: Short-course preoperative radiation (SCRT) with delayed surgery was found to increase pathologic complete response (pCR) rates in several trials. However, there was no clear answer on whether SCRT or long-course chemo-radiotherapy (LCRT) is more effective. Therefore we conducted this meta-analysis to evaluate the safety and efficacy of SCRT versus LCRT, both with delayed surgery, for treatment of rectal cancer. Materials and Methods: The literature was searched from PubMed, EMBASE, Web of Science, Cochrane Library and clinicaltrials.gov up to November, 2014. Quality of the randomized controlled trials (RCTs) was evaluated according to the Cochrane's risk of bias tool of RCT. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was used to rate the level of evidence. Review Manager 5.3 was employed for statistical analysis. Pooled risk ratios (RRs) and 95% confidence intervals (CIs) were calculated. Results: Three RCTs, with a total of 357 rectal cancer patients, were included in this systematic review. Metaanalysis results demonstrated there were no significantly differences in sphincter preservation rate, local recurrence rate, grade 3~4 acute toxicity, R0 resection rate and downstaging rate. Compared with SCRT, LCRT was associated with significant increase in the pCR rate [RR=0.49, 95%CI (0.31, 0.78), P=0.003]. Conclusions: In terms of sphincter preservation rate, local recurrence rate, grade 3~4 acute toxicity, R0 resection rate and downstaging rate, SCRT with delayed surgery is as effective as LCRT with delayed surgery for management of rectal cancer. LCRT significantly increased pCR rate compared with SCRT. Due to risk of bias and imprecision, further multi-center large sample RCTs were needed to confirm this conclusion.

Background: The objective of this study is to determine the effect of nursing education on awareness of risk factors for colorectal cancer. Materials and Methods: In this descriptive study, the sample is consisted of 132 volunteer students studying in the 1st and 4th grades of School of Health Nursing Department during the fall semester of 2014-2015. Data were collected via a questionnaire including information on the socio-demographic features of the participants and the correlating risk factors of colorectal cancer, prepared by researchers in view of the literature. The questionnaire was distributed to students and completed during class time. Before presenting the questionnaires to the respondents, informed consent was obtained from each. The data obtained were analyzed with a statistical package (SPSS). At first, a Kolmogorov-Smirnow test was performed on the research data. However, since it was seen that variables did not have a normal distribution, the Wilcoxon Signed Ranks Test was applied. P values of <0.05 were considered statistically significant. Percentages, means and standard deviations were also utilized for evaluation. Results: Of the total of 132 students participating in this study, 85.6% (n=113) were female, and 14.4% (n=19) were male. The average age was $20.5{\pm}2.04$. 54.5 % of the students (n=72) were 4th graders and 45.5 % (n=60) were first graders. Total score averages of first graders on risk awareness was $X=12{\pm}7.24$, and fourth graders was $X=16.93{\pm}7.71$. The difference between these two scores were found to be statistically significant (Z= -9,333; p=0.000). Conclusions: Nursing education was found out to have a positive influence on the students' awareness of risk factors for colorectal cancer.

Background: Polymorphisms in the MDM2 309 (T>G) and TP53 72 (G>C) genes are reported to increase the susceptibility to head and neck cancer (HNC) in various populations. The risk for HNC is also strongly associated with etiologic habits such as smoking, alcohol consumption and/or chewing of betel quid (BQ). In a case-control study, we investigated the significance of the above polymorphisms alone, and upon interaction with one another as well as with various etiologic habits in determining HNC risk in a Northeast Indian population. Materials and Methods: Genotyping at 309 MDM2 and 72 TP53 in 122 HNC patients and 86 cancer free healthy controls was performed by PCR using allele specific primers, and the results were confirmed by DNA sequencing. Results: Individuals with the GG mutant allele of MDM2 showed a higher risk for HNC in comparison to those with the TT wild type allele (OR=1.9, 95%CI: 1.1-3.3) (p=0.022). The risk was further increased in females by ~4-fold (OR=4.6, 95% CI: 1.1-19.4) (P=0.04). TP53 polymorphism did not contribute to HNC risk alone; however, interaction between the TP53 GC and MDM2 GG genotypes resulted in significant risk (OR=4.9, 95% CI: 0.2-105.1) (p=0.04). Smokers, BQ- chewers and alcohol consumers showed statistically significant and dose-dependent increase in HNC risk, irrespective of the MDM2 genotype. Conclusions: MDM2 genotype could serve as an important predictive biomarker for HNC risk in the population of Northeast India.

Background: Oral squamous cell carcinoma (OSCC) is thought to develop from precancerous dysplastic lesions through multistep processes of carcinogenesis involving activation of oncogenes and loss of tumor suppressor genes. The human epidermal growth factor receptor 2 (Her-2/neu [erbB-2]), a cell membrane glycoprotein, is a growth factor receptor that has receptor tyrosine kinase activity. Her2/neu activation plays a central role in cell proliferation and survival. It has been shown that overexpression of Her2/neu increases the rate of cell division and growth, leading to precancerous changes. The aim of the present study was to compare the serum and salivary Her2/neu levels between cases with premalignant and malignant oral lesions. Materials and Methods: Fasting blood samples and unstimulated saliva by passive drooling were collected from three groups of healthy control (n=20), premalignant disorder (PMD) (n=20) and OSCC (n=25) subjects. The HER2 extracellular domain (HER2 ECD) levels were measured using ELISA. Results: The levels of serum Her2/neu showed no significant differences between any of the groups but on the other hand salivary Her2/neu levels were found to be significantly (p<0.05) higher when compared between control (median 68.7 pg/ml, range: 21.5 - 75.8) and OSCC (median 145.6 pg/ml, range: 45.1-191.1). A similar trend was observed when comparing between PMD (median 43.3, range: 22.1 -94.7) and OSCC with a statistical significance of p<0.05. Conclusions: Our study provided evidence of increased salivary Her2/neu in OSCC when compared to PMD and control which was not the case for serum levels. This suggests that probably Her2/neu is not highly amplified as in breast cancer so as to be reflected in serum. Since saliva is in local vicinity of the OSCC, even a mild increase might be mirrored. On the whole, this study proposes Her2/neu as marker for distinguishing premalignant and malignant conditions.

The present study was designed to investigate cholangiocarcinoma (CCA) antibodies in hamster serum. Hamster CCA cell lines were processed using sodium dodecyl sulfate-polyacrylamide gel electrophoresis and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. A candidate biomarker was confirmed by immunoprecipitation and western blot, and was further analyzed using ELISA and sera from normal control hamsters, hamsters with opisthorchiasis and hamsters with various stages of CCA, as well as from CCA patients and healthy individuals. One candidate marker was identified as $HSP90{\alpha}$, as indicated by a high level of anti-$HSP90{\alpha}$ in hamster CCA sera. It was found that the levels of anti-$HSP90{\alpha}$ were specifically elevated in the sera of hamsters with CCA compared with other groups and progressively increased with the clinical stage. At the cut-off point of 0.4850 on the receiver operating characteristic curve, anti-$HSP90{\alpha}$ could discriminate CCA from healthy control groups with a sensitivity of 76.2%, specificity of 71.4% and total accuracy 75.5%. In the present study, we have shown that anti-$HSP90{\alpha}$ may be a potential useful serum biomarker to discriminate CCA cases from healthy persons.

Background: Reported age standardized incidence rates for esophageal cancer in Iran are 0.88 and 6.15 for females and males, at fifth and the eighth ranks, respectively, of cancers overall. The present study aimed to map relative risk using more realistic and less problematic methods than common estimators. Materials and Methods: In this ecological investigation, the studied population consisted of all esophageal cancer patients in Iran from 2005 to 2007. The Bayesian multilevel space-time model with three levels of county, province, and time was used to measure the relative risk of esophageal cancer. Analyses were conducted using R package INLA. Results: The total number of registered patients was 7,160. According to the results, the three-level model with adjustment for risk factors of physical activity and smoking had the best fit among all models. The overall temporal trend was significantly increasing. At county level, Ahar, Marand, Salmas, Bojnoord, Saghez, Sarakhs, Shahroud and Torbatejam had the highest relative risks. Physical activity was found to have significant direct association with risk of developing esophageal cancer. Conclusions: Given to great variation across geographical areas, many different factors affect the incidence of esophageal cancer. Conducting further studies at the individual level in areas with high incidence could provide more detailed information on risk factors of esophageal cancer.

Background: Outcome-expectation beliefs and knowledge may ultimately influence behavior for cancer prevention. The aims of this study were to measure changes in knowledge and beliefs about cancer prevention before and after viewing a television advertisement and identify the factors affecting receptivity to its messages. Materials and Methods: A one-group pretest-posttest design was used in this study of 1,000 individuals aged 20 to 65 years who were recruited online in November 2014. The outcome variables included cancer prevention beliefs based on the Health Belief Model (five items) and knowledge about risk factors for cancer (seven items). Results: Perceived susceptibility, perceived benefits, and self-efficacy increased significantly and their perceived severity and perceived barriers decreased significantly, after participants viewed the television advertisement. Correct responses to questions about risk factors also increased significantly, except for smoking. The main factors affecting changes in the outcome variables were age, interest in cancer prevention, social network, satisfaction with the ad, and pretest scores. Conclusions: Television advertisements with positive frameworks can be an efficient channel of improving beliefs and knowledge about cancer prevention in a short period. The continuous development of intervention materials that consider the demographics, needs, and satisfaction of the target group will be necessary for future studies.

As a cytosolic transcription factor, the aryl hydrocarbon (Ah) receptor is involved in several pathophysiological events leading to immunosuppression and cancer; hence antagonists of the Ah receptor may possess chemoprevention properties. It is known to modulate carcinogen-metabolising enzymes, for instance the CYP1 family of cytochromes P450 and quinone reductase, both important in the biotransformation of many chemical carcinogens via regulating phase I and phase II enzyme systems. Utilising chemically-activated luciferase expression (CALUX) assay it was revealed that intact glucosinolates, glucoraphanin and glucoerucin, isolated from Brassica oleracea L. var. acephala sabellica and Eruca sativa ripe seeds, respectively, are such antagonists. Both glucosinolates were poor ligands for the Ah receptor; however, they effectively antagonised activation of the receptor by the avid ligand benzo[a]pyrene. Indeed, intact glucosinolate glucoraphanin was a more potent antagonist to the receptor than glucoerucin. It can be concluded that both glucosinolates effectively act as antagonists for the Ah receptor, and this may contribute to their established chemoprevention potency.

Background: Ovarian cancer is the most common gynecological malignancy and constitutes the fifth leading cause of female cancer death. Some biological parameters have prognostic roles in patients with advanced ovarian cancer and their expression may contribute to tumor progression. The aim of this study was to investigate the potential prognostic value of SKP2, genes P27Kip1, K-ras, c-Myc, COX2 and HER2 genes expression in ovarian cancer. Materials and Methods: This study was performed on two hundred formalin fixed paraffin embedded ovarian cancer and normal adjacent tissues (NAT). Gene expression levels were assessed using real time PCR and Western blotting. Results: Elevated expression levels of SKP2, K-ras, c-Myc, HER2 and COX2 genes were observed in 61.5% (123/200), 92.5% (185/200), 74% (148/200), 96 % (192/200), 90% (180/200) and 78.5% (157/200) of cancer tissues, respectively. High expression of SKP2 and down-regulation of P27 was associated with advanced stages of cancer. Conclusions: The association between high expression of c-Myc and SKP2 with low expression of P27 suggested that the Skp2-P27 pathway may play an important role in ovarian carcinogenesis. Reduced expression of P27 is associated with advanced stage of cancer and can be used as a biological marker in clinical routine assessment and management of women with advanced ovarian cancer.

The developing countries have higher mortality rates for breast cancer. A reason for this is presentation at advanced stages due to low levels of public awareness. Activities are arranged by health authorities of developing countries to increase the knowledge of women but their effectiveness has not been evaluated in detail. A multiple choice questionnaire with questions about socio-demographic profile and questions about breast cancer knowledge was designed in local language Urdu, to evaluate the knowledge of the participants before and after an audio visual educational activity in Lahore, Pakistan. Scores of 0-2, 3-5 and 6-8 were ranked as poor, fair and good, respectively. Among 146 participants these scores were achieved by 1%, 55% and 45% before activity and 0%, 16% and 84% after the activity. Overall 66% of participants increased their knowledge score. Younger age, higher education, reliance on television as source of information and being a housewife were associated with better impact of the awareness activity. For the six knowledge related questions 3%, 5%, 11%, 23%, 33% and 44% more participants gave correct answers after the activity. However 6% and 7% fewer participants answered correctly for 2 questions related to the cause and the best prevention for breast cancer. The study indicated that awareness activities are effective to increase the knowledge of women and better impact is associated with higher education and younger age of women. The component analysis showed that the questions and related presentations using medical terms have a negative impact and should not therefore be used. Analysis of activity therefore leads to identification of deficiencies which can be remedied in future.

Micronutrients in food have been found to have chemopreventive effects, supporting the conclusions from epidemiologie studies that consumption of fresh fruits and vegetables reduces cancer risk. The present study was carried out to evaluate the role of querctin (Q) and sodium gluconate (GNA) supplementation separately or in combination in ameliorating promotion of colon tumor development by dimethyl-hydrazine (DMH) in mice. Histopathological observation of colons in mice treated with DMH showed goblet cell dysplasia with inflammatory cell infiltration. This pathological finding was associated with significant alteration in oxidative stress markers in colon tissues and carcinoembryonic antigen (CEA) levels in plasma. Mice co-treated with GNA and Q showed mild changes of absorptive and goblet cells and inflammatory cell infiltration in lamina properia, with improvement in oxidative stress markers. In conclusion, findings of the present study indicate significant roles for reactive oxygen species (ROS) in pathogenesis of DMH-induced colon toxicity and initiation of colon cancer. Also, they suggest that Q, GNA or the combination of both have a positive beneficial effect against DMH induced colonic cancer induction in mice.

Objective: To describe and analyze the epidemiological characteristics of lung cancer mortality in China from 1991 to 2013, forecast the future five-year trend and provide scientific evidence for prevention and management of lung cancer. Materials and Methods: Mortality data for lung cancer in China from 1991 to 2013 were used to describe epidemiological characteristics. Trend surface analysis was applied to analyze the geographical distribution of lung cancer. Four models, curve estimation, time series modeling, gray modeling (GM) and joinpoint regression, were performed to forecast the trend for the future. Results: Since 1991 the mortality rate of lung cancer increased yearly. The rate for males was higher than that for females and rates in urban areas were higher than in rural areas. In addition, our results showed that the trend will continue to increase in the ensuing 5 years. The mortality rate increased from age 45-50 and peaked in the group of 85 years old. Geographical analysis indicated that people living in northeast China provinces and the coastal provinces in eastern China had a higher mortality rate for lung cancer than those living in the centre or western Chinese provinces. Conclusions: The standardized mortality rate of lung cancer has constantly increased from 1991 to 2013, and been predicted to continue in the ensuing 5 years. Further efforts should be concentrated on education of the general public to increase prevention and early detection. Much better prevention and management is needed in high mortality areas (northeastern and eastern parts of China) and high risk populations (45-50-year-olds).

Background: Melatonin, which is mainly produced by the pineal gland, has a good inhibitory effect on cell growth of multiple cancer types. However, the underlying molecular mechanisms of anti-tumor activity for colon cancer have not been fully elucidated. In this study, we investigated the effects of melatonin on migration in human colon cancer RKO cells and the potential molecular mechanisms. Materials and Methods: The viability of RKO cells was investigated by MTT assay after treatment with melatonin, SB203580 (p38 inhibitor) and phorbol 12-myristate 13-acetate (PMA, MAPK activator) alone or in combination for 48h. The effects of melatonin, and ML-7, a selective inhibitor of myosin light chain kinase (MLCK), and SB203580, and PMA on the migration of RKO cells were analyzed by in vitro scratch-wound assay. The relative mRNA levels of MLCK was assessed by real-time quantitative RT-PCR. Western blotting analysis was performed to examine the expression of MLCK, phosphorylation of myosin light chain (pMLC) and p38 (pp38). Results: The proliferation and migration of human colon cancer RKO cells were inhibited significantly after treatment with melatonin. The expression levels of MLCK and phosphorylation of MLC of RKO cells were reduced, and real-time quantitative RT-PCR showed that melatonin had significant effects on suppressing the expression of MLCK. Furthermore, the phosphorylation level of p38, which showed the same trend, was also reduced when cells were treated by melatonin. In addition, ML-7 (25umol/l) could down-regulate the phosphorylation of p38. Conclusions: Melatonin could inhibit the proliferation and migration of RKO cells, and further experiments confirmed that p38 MAPK plays an important role in regulating melatonin-induced migration inhibition through down-regulating the expression and activity of MLCK.

Background: Detection of cervical high grade lesions in patients with atypical squamous cells of undetermined significance (ASCUS) is still a challenge. Our study tested the efficacy of the paired boxed gene 1 (PAX1) methylation analysis by methylation-sensitive high-resolution melting (MS-HRM) in the detection of high grade lesions in ASCUS and compared performance with the hybrid capture 2 (HC2) human papillomavirus (HPV) test. Materials and Methods: A total of 463 consecutive ASCUS women from primary screening were selected. Their cervical scrapings were collected and assessed by PAX1 methylation analysis (MS-HRM) and high-risk HPV-DNA test (HC2). All patients with ASCUS were admitted to colposcopy and cervical biopsies. The Chisquare test was used to test the differences of PAX1 methylation or HPV infection between groups. Results: The specificity, sensitivity, and accuracy for detecting CIN2 + lesions were: 95.6%, 82.4%, and 94.6%, respectively, for the PAX1 MS-HRM test; and 59.7%, 64.7%, and 60.0% for the HC2 HPV test. Conclusions: The PAX1 methylation analysis by MS-HRM demonstrated a better performance than the high-risk HPV-DNA test for the detection of high grade lesions (CIN2 +) in ASCUS cases. This approach could screen out the majority of low grade cases of ASCUS, and thus reduce the referral rate to colposcopy.

Background: Smoking behavior is related to numerous factors, including psychosocial parameters. This study investigated the association between family context factors and smoking among male adolescents. Materials and Methods: A cross-sectional, school-based study was conducted during 2014. The study sampled 900 students from intermediate and secondary schools in Madinah City, Saudi Arabia. Data concerning smoking status, sociodemographic, parental and friends' smoking behavior, and family factors were collected using a self-administered questionnaire. These data were employed to estimate the prevalence of smoking using appropriate statistical analyses including multivariate logistic regression. Results: Of 900 students, 870 completed the study questionnaire (96.7%). Of the respondents, 181 students (20.8%, 95% CI=18.1%-23.5%) were current smokers, and a much higher prevalence was observed among adolescents with most or all of their friends smoking (48.1%) and those living with neither parent (47.4%). The adjusted risk of smoking increased significantly among adolescents who lived with neither parent (OR=3.3; 95% CI=1.1-9.2) and among those who reported little or no parental supervision (OR=1.5; 95% CI=1.0-2.1). Conclusions: Family context factors are associated with an increased risk of smoking behavior among male adolescents in Saudi Arabia.

Background: The survival rate reflecting prognosis of breast cancer patients is usually estimated based on crude survival methods such as observed and cause-specific. In situations where data are based on population-cancer registries, this method may produce biased estimations. This study therefore aimed to estimate the net survival of breast cancer based on relative survival. Materials and Methods: Data for 622 breast cancer patients diagnosed at the Iran Cancer Institute during 1990-95 and tracked till the end of 2000 were analyzed. For estimation of relative survival, Ederer's second method and SAS (9.1) and STATA (11) software were used. Results: Threeyear relative survivals of 85%, 90%, 80% and 67% were observed for age groups 15-44, 55-59, 60-74, and 75+years-old, respectively. A relative survival of approximately one was observed for two subsequent years for age-group 45-59 years-old. A value greater than one for two subsequent years of follow-up was observed in the age-group 60-74 years-old. Conclusions: Tracking the diagnosis of breast cancer, the relative survival decreases as we go to higher age-groups. It is also perceived that through follow-up, relative survival first decreased and then increased a little. The statistical cure point is acceptable for age group 45-59 years-old while for age-groups 15-44 and 60-74 years old is a sign of low quality data for some follow-up intervals.

Background: Kidney cancer has shown an increasing trend in recent decades. This study aimed to determine change in the incidence rate between 2003 and 2009 in Iran. Materials and Methods: In this study, national cancer registry data were used. Crude incidence rates were calculated per 100,000 and age-standardized incidence rates (ASRs) were computed using the direct standardization method and the world standard population. Significant trend of incidence rates was examined by the Cochran-Armitage test for linear trend. Results: A total of 6,944 cases of kidney cancer were reported. The incidence cases increased from 595 patients in 2003 to 1,387 patients in 2009. Sex ratio (male to female) was 1.67. ASR also increased from 1.18 in 2003 to 2.52 in 2009 per 100,000, but the increasing trend was not significant. Conclusions: A slow increasing trend of incidence rate was observed in the study population. This may be due to an increase of risk factors. It is suggested to perform a study on risk factors for the cancer.

Nicotine-derived nitrosamine ketone (NNK) is considered a key tobacco smoke carcinogen inducing lung tumors. Physalis peruviana L (harankash) is considered one plant with marked health benefits. This study aimed to evaluate Physalis peruviana L effect on the toxic effect of NNK induced lung cancer in the rats by using pulmonary histopathological, immunohistochemical and DNA flow cytometric analyses. Sixty adult male rats were divided into four groups, each consisting of fifteen animals. The first group received saline, the second received two successive toxic doses of NNK only while the third received two successive toxic doses of NNK with a single daily dose of Physalis peruviana L. The fourth group received a single daily dose of Physalis peruviana L only. Toxic doses of NNK induced hyperplasia and adenocarcinoma in the lung and positive immunoreactivity for Ki-67 and p53 staining with disturbance of the lung DNA content. Administration of Physalis peruviana L with NNK led to a mild pulmonary hyperplasia and weak expression of Ki-67 and p53 with an improvement in the lung DNA content. Physalis peruviana L may protect against NNK induced lung carcinogenesis due to its antioxidant and anti-proliferative effects.

Background: Breast and cervical cancers are among the most frequent and most fatal cancers in women. Life span of patients may be increased and quality of life improved through early diagnosis and treatment. This investigation was performed in order to determine knowledge and practices of female health personnel working at a university hospital regarding breast and cervical cancers. Materials and Methods: This descriptive investigation was performed in Erciyes University Hospitals in 2014. A total of 524 female health personnel were included in the study. Data were collected through a questionnaire of 36 questions prepared by the researchers. The Chi square test and logistic regression were used for statistical analyses. Results: The mean age of the study group was $32.8{\pm}6.9$ years, 18.3% being doctors and 81.7% nurses. Of the study group, 60.5% stated that they performed self breast-examination, 4.4% underwent HPV testing, 26.3% thought about taking an HPV test, 34.7% of those who are 40 years and over had mammography regularly and 19.5% of those who were married had a Pap smear conducted regularly. Most important causes of not performing the methods for early diagnosis of breast and cervical cancers are "forget and neglect". Conclusions: It was concluded that female doctors and nurses do not pay sufficient attention to screening programs for breast and cervical cancers. The importance of early diagnosis and treatment should be emphasized during the undergraduate education and in-service training programs. Health condition of personnel and their utilization of preventive health care should be followed by occupational physicians.

Cholangiocarcinoma (CCA) is a rare but highly fatal cancer for which the molecular mechanisms and diagnostic markers are obscure. We therefore investigated the kinetic expression of isocitrate dehydrogenase-1 (IDH1), isocitrate dehydrogenase-2 (IDH2) and homogentisate 1,2-dioxygenase (HGD) during the tumorigenesis of O. viverrini infection-associated CCA in an animal model, and confirmed down-regulation of expression in human cases of opisthorchiasis-associated CCA through real time PCR. Kinetic expression of HGD, IDH1 and IDH2 in the animal model of O. viverrini infection-induced CCA was correlated with human CCA cases. In the animal model, expression of HGD was decreased at all time points (p<0.01) and expression of both IDH1 and IDH2 was decreased in the CCA group. In human cases, expression of HGD, IDH1 and IDH2 was decreased more than 2 fold in 55 cases (70.5%), 25 cases (32.1%) and 24 cases (30.8%) respectively. The present study suggests that reduction of HGD, IDH1 and IDH2 may be involve in cholangiocarcinoma genesis and may be useful for molecular diagnosis.

Despite recent advances in therapeutic strategies for lung cancer, mortality still is increasing. In the present study, we investigated the anti-cancer effects of KMU-193, 2-(4-Ethoxy-phenyl)-N-{5-[2-fluoro-4-(4-methylpiperazine-1-carbonyl)-phenylamino]-1H-indazol-3-yl}-acetamide in a human non-small cell lung cancer cell line A549. KMU-193 strongly inhibited the proliferation of A549 cells, but it did not have anti-proliferative effect in other types of cancer cell lines. KMU-193 further induced apoptosis in association with activation of caspase-3 and cleavage of PLC-${\gamma}1$. However, KMU-193 had no apoptotic effect in untransformed cells such as TMCK-1 and BEAS-2B. Interestingly, pretreatment with z-VAD-fmk, a pan-caspase inhibitor, strongly abrogated KMU-193-induced apoptosis. KMU-193 treatment enhanced the expression levels of p53 and PUMA. Importantly, p53 siRNA transfection attenuated KMU-193-induced apoptosis. Collectively, these results for the first time demonstrate that KMU-193 has strong apoptotic effects on A549 cells and these are largely mediated through caspase-3- and p53-dependent pathways.

Background: The performance of combined testing visual inspection with acetic acid (VIA) and cervical cytology tests might differ from one setting to another. The average estimate of the testing accuracy across studies is informative, but no meta-analysis has been carried out to assess this combined method. Objective: The objective of this study was to estimate the average sensitivity and specificity of the combined VIA and cervical cytology tests for the detection of cervical precancerous lesions. Materials and Methods: We conducted a systematic review and a meta-analysis, according to the Cochrane Handbook for Systematic Review of Diagnostic Test Accuracy. We considered two cases. In the either-positive result case, a positive result implies positivity in at least one of the tests. A negative result implies negativity in both tests. In the both-positive case, a positive result implies having both tests positive. Eligible studies were identified using Pubmed, Embase, Website of Science, CINHAL and COCRANE databases. True positive, false positive, false negative and true negative values were extracted. Estimates of sensitivity and specificity, positive and negative likelihood (LR) and diagnostic odds ratios (DOR) were pooled using a hierarchical random effect model. Hierarchical summary receiver operating characteristics (HSROC) were generated and heterogeneity was verified through covariates potentially influencing the diagnostic odds ratio. Findings: Nine studies fulfilled inclusion criteria and were included in the analysis. Pooled estimates of the sensitivities of the combined tests in either-positive and both-positive cases were 0.87 (95% CI: 0.83-0.90) and 0.38 (95% CI: 0.29-0.48), respectively. Corresponding specificities were 0.79 (95% CI: 0.63-0.89) and 0.98 (95% CI: 0.96-0.99) respectively. The DORs of the combined tests in either-positive or both-positive result cases were 27.7 (95% CI: 12.5-61.5) and 52 (95% CI: 22.1-122.2), respectively. When including only articles without partial verification bias and also a high-grade cervical intraepithelial neoplasia as a threshold of the disease, DOR of combined test in both-positive result cases remained the highest. However, DORs decreased to 12.1 (95% CI: 6.05-24.1) and 13.8 (95% CI: 7.92-23.9) in studies without partial verification bias for the combined tests in the either-positive and both-positive result cases, respectively. The screener, the place of study and the size of the population significantly influenced the DOR of combined tests in the both-positive result case in restriction analyses that considered only articles with CIN2+ as disease threshold. Conclusions: The combined test in the either-positive result case has a high sensitivity, but a low specificity. These results suggest that the combined test should be considered in developing countries as a primary screening test if facilities exist to confirm, through colposcopy and biopsy, a positive result.

Background: To compare the current histologic distribution of lung cancer in Lebanon to the worldwide trends, according to the 2004 WHO Classification. Materials and Methods: 1,760 patients with a pulmonary pathology examination at Hotel-Dieu de France University Hospital between July 2009 and July 2014 were included. Results: Some 676 out of the total investigated patients (38.4%) had a lung tumor. In 665 (98.4%) the tumors were malignant, with a mean age at diagnosis of 63.8 years and a male/female (M/F) sex ratio of 1.7:1. Among the malignant tumors, 86.2% were epithelial tumors with a mean age at diagnosis of 64.8 years and an M/F sex ratio of 1.9. Other malignant tumors consisted of metastatic tumors (10.2%), lymphoproliferative tumors (2.1%) and mesenchymal tumors (1.5%). Most common carcinoma subtypes were adenocarcinoma (48.0%), squamous cell carcinoma (23.0%) and small cell carcinoma (13.3%). Carcinoid tumors were the only carcinoma subtype with an M/F sex ratio below 1 (0.7). Salivary gland tumors were the carcinoma with lowest mean age at diagnosis (45.5 years). Conclusions: The histologic distribution of lung tumors in Lebanon is similar to that in developed countries. We believe this resemblance is due to common smoking habits, known to be responsible for the increase of lung adenocarcinoma at the expense of other subtypes.

Background: Cholangiocarcinoma (CCA) is a serious public health problem in the Northeast of Thailand. CCA is considered to be an incurable and rapidly lethal disease. Knowledge of the distribution of CCA patients is necessary for management strategies. Objectives: This study aimed to utilize the Geographic Information System and Google $Earth^{TM}$ for distribution mapping of cholangiocarcinoma in Satuek District, Buriram, Thailand, during a 5-year period (2008-2012). Materials and Methods: In this retrospective study data were collected and reviewed from the OPD cards, definitive cases of CCA were patients who were treated in Satuek hospital and were diagnosed with CCA or ICD-10 code C22.1. CCA cases were used to analyze and calculate with ArcGIS 9.2, all of data were imported into Google Earth using the online web page www.earthpoint.us. Data were displayed at village points. Results: A total of 53 cases were diagnosed and identified as CCA. The incidence was 53.57 per 100,000 population (65.5 for males and 30.8 for females) and the majority of CCA cases were in stages IV and IIA. The average age was 67 years old. The highest attack rate was observed in Thung Wang sub-district (161.4 per 100,000 population). The map display at village points for CCA patients based on Google Earth gave a clear visual deistribution. Conclusions: CCA is still a major problem in Satuek district, Buriram province of Thailand. The Google Earth production process is very simple and easy to learn. It is suitable for the use in further development of CCA management strategies.

Purpose: To evaluate and update evidence for prognostic effects of kidney-sparing (KS) management and nephroureterectomy (NU) for upper tract urothelial carcinomas. Materials and Methods: Pubmed, Embase and the Cochrane Library were retrieved for the identification of comparative studies of kidney-sparing procedure and nephroureterectomy for upper tract urothelial carcinoma prior to December 2014. The data were extracted independently by 2 reviewers and the quality of the included studies was assessed. Review Manager 5.3 and STATA 13 were used to perform the meta-analysis. Results: Twenty-three observational studies including 1,587 KS and 3,996 NU were evaluated. The results of the meta-analysis showed that nephroureterectomy had no significant benefit with regard to intravesical recurrence (IRFS), metastasis (MFS), cancer specific survival (CSS) and overall survival (OS) except the total tumor recurrence (RFS) when compared with kidney sparing management. The respectively pooled outcomes were HR 1.36 (0.69-2.68, P=0.38) for IRFS, 1.09 (0.59-2.01, P=0.78) for MFS, 1.17 (0.77-1.79, P=0.47) for CSS, 1.50 (0.90-2.48, P=0.12) for OS and 1.61 (1.03-2.51, P=0.04) for RFS. Conclusions: On the whole, kidney-sparing management had equivalent prognostic effect on upper tract urothelial carcinoma as the standard nephroureterectomy except in tumor recurrence. However, the results should be interpreted with caution for lack of stage and grade stratification and multi-center randomized controlled trials are still needed to verify our results.

Gestational trophoblastic neoplasia (GTN) is the malignant form of gestational trophoblastic disease. In non-metastatic GTN, the outcomes of treatment are impressive with methotrexate (MTX) or actinomycin D. We retrospectively reviewed the outcomes of non-metastatic GTN treated at our center from January, 1999 to December, 2013. One hundred and nine patients were recruited to the study. The median age was 33.1 years and over 90% were referral cases. Abnormal vaginal symptoms developed in 37.6% while 56.4% were asymptomatic. The most common antecedent pregnancy was a complete mole (92.7%) with the median interval time from antecedent pregnancy to GTN development being 2.0 months. The median pretreatment B-hCG was 5,624 mIu/ml. The most common first line treatment was methotrexate (MTX) and folinic acid (91.7%) followed by weekly MTX (4.6%), etoposide+ MTX+actinomycin D (EMA) (2.8%), and actinomycin D (0.9%), with the median number of cycles at 5.0. The positive response to first line chemotherapy was 73.8%. The patients were given subsequent chemotherapeutic regimens after resistance to the first line therapy and showed a final remission rate of 89.9%.The significant factor that was frequently found in patients who were non-responders to the first line treatment was a hysterectomy procedure. Two patients developed lung metastasis and brain metastasis at one and four years after the first treatment, respectively. In conclusion, the outcomes of non-metastatic GTN were excellent. However, the patients need long term follow up due to the possibility of developing multiple organ metastases.

Background: Prostate cancer is the most commonly diagnosed form of cancer and the sixth leading cause of cancer-related deaths among men in the entire world. Reported standardized incidence rates are 12.6, 61.7, 11.9 and 27.9 in Iran, developed countries, developing countries and the entire world, respectively. The present study investigated the relative risk of PC in Iran at the province level and also explored the impact of some factors by the use of Bayesian models. Materials and Methods: Our study population was all men with PC in Iran from 2005 to 2008. Considered risk factors were smoking, fruit and vegetable intake, physical activity, obesity and human development index. We used empirical and full Bayesian models to study the relative risk in Iran at province level to estimate the risk of PC more accurately. Results: In Iran from 2005 to 2008 the total number of known PC cases was 10,361 with most cases found in Fars and Tehran and the least in Ilam. In all models just human development index was found to be significantly related to PC risk Conclusions: In the unadjusted model, Fars, Semnam, Isfahan and Tehran provinces have the highest and Sistan-and-Baluchestan has the least risk of PC. In general, central provinces have high risk. After adjusting for covariates, Fars and Zanjan provinces have the highest relative risk and Kerman, Northern Khorasan, Kohgiluyeh Boyer Ahmad, Ghazvin and Kermanshah have the lowest relative risk. According to the results, the incidence of PC in provinces with higher human development index is higher.

Background: Registry data from four major public hospitals indicate trends over three decades from 1980 to 2010 in treatment and survival from colorectal cancer with distant metastases at diagnosis (TNM stage IV). Materials and Methods: Kaplan-Meier product-limit estimates and Cox proportional hazards models for investigating disease-specific survival and multiple logistic regression analyses for indicating first-round treatment trends. Results: Two-year survivals increased from 10% for 1980-84 to 35% for 2005-10 diagnoses. Corresponding increases in five-year survivals were from 3% to 16%. Time-to-event risk of colorectal cancer death approximately halved (hazards ratio: 0.48 (0.40, 0.59) after adjusting for demographic factors, tumour differentiation, and primary sub-site. Survivals were not found to differ by place of residence, suggesting reasonable equity in service provision. About 74% of cases were treated surgically and this proportion increased over time. Proportions having systemic therapy and/or radiotherapy increased from 12% in 1980-84 to 61% for 2005-10. Radiotherapy was more common for rectal than colonic cases (39% vs 7% in 2005-10). Of the cases diagnosed in 2005-10 when less than 70 years of age, the percentage having radiotherapy and/or systemic therapy was 79% for colorectal, 74% for colon and 86% for rectum (&RS)) cancers. Corresponding proportions having: systemic therapies were 75%, 71% and 81% respectively; radiotherapy were 24%, 10% and 46% respectively; and surgery were 75%, 78% and 71% respectively. Based on survey data on uptake of offered therapies, it is likely that of these younger cases, 85% would have been offered systemic treatment and among rectum (&RS) cases, about 63% would have been offered radiotherapy. Conclusions: Pronounced increases in survivals from metastatic colorectal cancer have occurred, in keeping with improved systemic therapies and surgical interventions. Use of radiotherapy and/or systemic therapy has increased markedly and patterns of change accord with clinical guideline recommendations.

Background: We aimed to investigate the prognostic value of baseline neutrophil, lymphocyte, and platelet counts along with the neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) in local and advanced gastric cancer patients. Materials and Methods: In this retrospective cross-sectional study, a total of 103 patients with gastric cancer were included. For all, patient characteristics and overall survival (OS) times were evaluated. Data from a complete blood count test including neutrophil, lymphocyte, monocyte, white blood cell (WBC) and platelet (Plt) count, hemoglobin level (Hb) were recorded, and the NLR and PLR were obtained for every patient prior to pathological diagnosis before any treatment was applied. Results: Of the patients, 53 had local disease, underwent surgery and were administered adjuvant chemoradiotherapy where indicated. The remaining 50 had advanced disease and only received chemotherapy. OS time was $71.6{\pm}6$ months in local gastric cancer patients group and $15{\pm}2$ months in the advanced gastric cancer group. Univariate analysis demonstrated that only high platelet count (p=0.013) was associated with better OS in the local gastric cancer patients. In contrast, both low NLR (p=0.029) and low PLR (p=0.012) were associated with better OS in advanced gastric cancer patients. Conclusions: This study demonstrated that NLR and PLR had no effect on prognosis in patients with local gastric cancer who underwent surgery and received adjuvant chemoradiotherapy. In advanced gastric cancer patients, both NLR and PLR had significant effects on prognosis, so they may find application as easily measured prognostic factors for such patients.

Background: There is still a great deal of controversy with regard to the prognostic role of chemotherapy-induced amenorrhea (CIA) in breast cancer patients. To confirm whether CIA can serve as a useful factor in predicting clinical effects of systemic adjuvant chemotherapy, we performed this meta-analysis. Materials and Methods: Relevant studies were identified using PubMed, and Embase databases. Eligible study results were pooled and summary hazard ratios (HRs) with corresponding confidence intervals (CIs) were calculated. Subgroup analyses and an assessment of publication bias were also conducted. Results: A total of 8,333 patients from 11 published studies were identified through searching the databases. The pooled HRs for disease-free survival (DFS) suggested that CIA was associated with a significant reduction in the risk of recurrence, especially in patients with hormone receptor-positive lesions (overall HR=0.65, 95%CI 0.53-0.80, $I^2=41.3%$). When the five studies reporting the HR for overall survival (OS) were pooled (n=4193), a favorable trend was found (HR=0.69, 95%CI 0.52-0.91, $I^2=51.6%$). No publication bias was observed in this study. Conclusions: This meta-analysis suggests that CIA predicts a better outcome in premenopausal hormone receptor-positive breast cancer patients.

A 6-year retrospective cohort study was conducted among Thai hematologic malignancy (HM) patients receiving intensive chemotherapy. Of the 145 eligible patients receiving 893 chemotherapy sessions, 46.9% were female, median age was 52 years, and the most common HM diagnosis was diffuse large B-cell lymphoma (46.2%). Febrile neutropenia (FN) occurred in 14.9% of chemotherapy sessions with an incidence of 24.8 per 1,000 chemotherapy cycles per year. Independent factors associated with FN were receiving the first chemotherapy cycle [adjusted hazard ratio (aHR) 4.1], having hemoglobin ${\leq}100g/L$ (aHR 3.7) and platelet ${\leq}140,000/{\mu}L$ (aHR 2.7) on chemotherapy day and receiving acute myeloid leukemia regimens (aHR 20.8). Granulocyte colony stimulating factor was significantly associated with reduced rate of FN when given in those receiving CHOP regimen. With the median follow-up time of 16 months, the overall survival time was significantly longer in patients without FN than those with FN (61.7 vs. 20.8 months; p<0.001).

Background: To evaluate the rate of pathologic high-risk factors, intermediate-risk factors, and treatment outcomes in early-stage cervical cancer patients undergoing radical hysterectomy and pelvic lymphadenectomy (RHPL). Materials and Methods: Medical records of stage IA-IIA1 cervical cancer patients who underwent RHPL during the 2006 to 2012 time period and patient follow-up data until December 2013 were reviewed. Results: Of 331 patients, 52 women (15.7%) had pathologic high-risk factors and 59 women (17.8%) had intermediate-risk factors without high-risk factors. All studied patients had an initial complete response. At median follow-up time of 40.9 months (range 1-103.3 months) and mean follow-up time of$ 43.3{\pm}25.3$ months, 37 women had disease recurrence and 4 women had died of disease. The most common site of recurrence was the pelvis (64.8%). Five-year and 10-year disease free survival rates were 96.1% and 91.5%, respectively. Five-year and 10-year overall survival rates were 100% and 99.4%, respectively. Independent factors related to recurrence were pelvic node metastasis (odds ratio [OR], 2.670; 95%CI, 1.001-7.119), and >1/3 cervical stromal invasion (OR, 3.763; 95%CI, 1.483-9.549). Conclusions: The rates of pathologic high-risk and intermediate-risk factors should be considered and disclosed when counseling patients regarding primary treatment by RHPL. Oncologic outcomes of primary surgical treatment for early-stage cervical carcinoma were found to be excellent.

Background: We designed this randomized controlled trial (RCT) to assess whether lobaplatin-based concurrent chemotherapy might be superior to cisplatin-based concurrent chemotherapy for FIGO stage II and III cervical cancer in terms of efficacy and safety. Materials and Methods: This prospective, open-label RCT aims to enroll 180 patients with FIGO stage II and III cervical cancer, randomly allocated to one of the three treatment groups (cisplatin $15mg/m^2$, cisplatin $20mg/m^2$ and lobaplatin $35mg/m^2$), with 60 patients in each group. All patients will receive external beam irradiation (EBRT) and high-dose-rate intracavitary brachytherapy (HDR-ICBT). Patients in cisplatin $15mg/m^2$ and $20mg/m^2$ groups will be administered four cycles of $15mg/m^2$ or $20mg/m^2$ cisplatin intravenously once weekly from the second week to the fifth week during EBRT, while patients inthe lobaplatin $35mg/m^2$ group will be administered two cycles of $35mg/m^2$ lobaplatin intravenously in the second and fifth week respectively during pelvic EBRT. All participants will be followed up for at least 12 months. Complete remission rate and progression-free survival (PFS) will be the primary endpoints. Overall survival (OS), incidence of adverse events (AEs), and quality of life will be the secondary endpoints. Results: Between March 2013 and March 2014, a total of 61 patients with FIGO stage II and III cervical cancer were randomly assigned to cisplatin $15mg/m^2$ group (n=21), cisplatin $20mg/m^2$ group (n=21) and lobaplatin $35mg/m^2$ group (n=19). We conducted a preliminary analysis of the results. Similar rates of complete remission and grades 3-4 gastrointestinal reactions were observed for the three treatment groups (P=0.801 and 0.793, respectively). Grade 3-4 hematologic toxicity was more frequent in the lobaplatin group than the cisplatin group. Conclusions: This proposed study will be the first RCT to evaluate whether lobaplatin-based chemoraiotherapy will have beneficial effects, compared with cisplatin-based chemoradiotherapy, on complete remission rate, PFS, OS, AEs and quality of life for FIGO stage II and III cervical cancer.

Background: This analysis was conducted to evaluate the efficacy and safety of a combination of gemcitabine and nedaplatin in treating patients with non-small cell lung cancer. Methods: Clinical studies evaluating the efficacy and safety of a combination of gemcitabine and nedaplatin with attention to response and safety for patients with non-small cell lung cancer were identified using a predefined search strategy. Pooled response rates for gemcitabine and nedaplatin were calculated. Results: In gemcitabine and nedaplatin based regimens, 4 clinical studies including 112 patients with non-small cell lung cancer were considered eligible for inclusion. The pooled analysis suggested that the pooled reponse rate was 40.2% (45/112). Main side effects included grade 3-4 neutropenia, thrombocytopenia, and anemia. Grade 3-4 nonhematological toxicity included nausea and vomiting, diarrhea, and hepatic dysfunction. There were no treatment-related deaths. Conclusion: This evidence based analysis suggests that the combination of gemcitabine and nedaplatin is associated with good response rate and accepted toxicity for treating patients with non-small cell lung cancer.

Background: The prevalence of prostate cancer is considered high in many countries, and screening tests are very important in order to detect prostate cancer in its early stages; however false positivity with these screening tests means that a lot of patients undergo unnecessary biopsy, which is an invasive procedure, for the confirmatory test. The purpose of this study was to estimate the frequency of unnecessary biopsy cases in patients referred for prostate biopsy in one of the most important and overload cancer centers in Syria. Materials and Methods: Retrospective data for a period of four years between January 2009 and December 2012 were collected in Al-Bayrouni University Medical hospital in Damascus, Syria. The patients from whom data were collected were referred to our histopathological department because of elevated prostate specific antigen (PSA) serum or an abnormal digital rectal examination (DRE). All patients underwent prostatic TRUS-guided biopsies. Diagnosis of prostate cancer (PCa) or benign prostatic hyperplasia (BPH) was based on histopathological examination and prostate cancers cases were graded and scored according to the Gleason score system. Results: For the 406 patients referred to biopsy, the $mean{\pm}SD$ age was $58.4{\pm}23.3$ years. The $mean{\pm}SD$ PSA level was $49.2{\pm}21.5ng/ml$. Of the total we found 237 patients diagnosed with PCa (58. 4%), 166 patients with BPH (40.9%) and 3 cases were unable to be diagnosed (0.7%) because of biopsy collection errors. Conclusions: Our study shows that a high percentage of patients are undergoing unnecessary biopsy, which suggests that the performed screening tests had a high level of false positive and may need re-evaluation.

Background: Several prognostic factors have been studied in NSCLC, although it is unknown which is most useful. In this study, we aimed to investigate whether pre-treatment serum albumin level has prognostic value in patients with Stage IIIB NSCLC. Materials and Methods: This cross-sectional study included a total of 204 patients with Stage IIIB NSCLC who met the inclusion criteria. Pre-treatment serum albumin levels and demographic, clinical, and histological characteristics, as well as laboratory variables were recorded. A cut-off value was defined for serum albumin level and the patients were stratified into four groups on thios basis. Results: The majority of the patients was males and smokers, with a history of weight loss, and squamous histological type of lung cancer. The mean serum albumin level was $3.2{\pm}1.7g/dL$ (range, 2.11-4.36 g/dL). A cut-off value 3.11 g/dL was set and among the patients with a lower level, 68% had adenocarcinoma and 82% were smokers. The patients with low serum albumin levels had a lower response rate to e first-line chemotherapy with a shorter progression-free survival and overall survival. Multivariate analysis showed that low serum albumin level was an independent poor prognostic factor for NSCLC. Conclusions: This study results suggest that low serum albumin level is an independent poor prognostic factor in patients with Stage IIIB NSCLC, associated with reduction in the response rate to first-line therapy and survival rates.

Background: Worldwide, breast cancer is the most common cancer diagnosed among women and a leading cause of cancer deaths. The age of onset in Iran has become reduced by a decade for unknown reasons. Herceptin, a humanized monoclonal antibody, is a target therapy for breast cancer cells with over expression of HER2-neu receptors, but it is an expensive drug with only 20% beneficial rate of survival. This study introduces a novel approach to enhance the efficacy of this drug through immunoconjugation of the antibody to botulinum toxin. Decreasing the cost and adverse effects of the antibody were secondary goals of this study. Materials and Methods: Botulinum toxin was conjugated with Herceptin using heterobifunctional cross linkers, succinimidyl acetylthiopropionate (SATP) and sulfo-succinimidyl-4-(N-maleimidomethyl) cyclohexane-1-carboxylate (SMCC) according to the supplier's guidelines and tested on two breast cancer cell lines: SK-BR-3 and BT-474. Toxin and Herceptin were also used separately as controls. The cytotoxicity assay was also performed using the new bioconjugate on cultured cells with Alamar blue and a fluorescence plate reader. Results: Herceptin-Toxin bioconjugation significantly improved Herceptin efficacy on both breast cancer cell lines when compared to the control group. Conclusions: Toxin-Herceptin bioconjugation can be a potential candidate with increased efficiency for treating breast cancer patients with over expression of the HER2 receptor.

Background: Serum 25-hydroxyvitamin D insufficiency is very common in Pakistan and is often related to inferior prognosis in some cancers but limited data exist for hematopoietic malignancies. This study was conducted to determine the vitamin D insufficiency in B-chronic lymphoid leukemia (CLL) cases at the time of presentation and its possible correlation with clinical staging, hematological parameters and biochemical markers. Materials and Methods: This descriptive cross sectional study was carried at Liaquat National Hospital from January 2011 to June 2013. Sixty patients with B-chronic lymphoid leukemia were enrolled. Complete blood count, vitamin D levels, serum urea, creatinine, uric acid and LDH levels were assessed. Data were compiled and analyzed using SPSS version 21. Results: Out of 60 patients, 42 (70%) were male and 18 (30%) were female. Mean age was $59.0{\pm}9.2years$. The frequency of vitamin D insufficiency was found to be 56.7%. Overall insufficiency was more frequently seen in male gender (40%). Vitamin D insufficiency demonstrated a positive association with low lactate dehydrogenase levels (P=0.005). No links were established with age, clinical stage, hematological and other biochemical markers. Conclusions: Vitamin D insufficiency is high compared with Western studies. Whether normalization of vitamin D insufficiency in deficient B-CLL patients could improve the clinical outcome or delay disease progression will require further studies.

Our previous study detected aflatoxins in red chili peppers from Chile, Bolivia, and Peru, each of which have a high incidence of gallbladder cancer (GBC). Since the aflatoxin B1 concentration was not so high in these peppers, it is important to clarify the presence of other mycotoxins. Here we attempted to determine any associations between the concentrations of aflatoxins and ochratoxin A (OTA) in red chili peppers, and the corresponding GBC incidences. We collected red chili peppers from three areas in Peru: Trujillo (a high GBC incidence area), Cusco (an intermediate GBC incidence area), and Lima (a low GBC incidence rate), and from Chile and Bolivia. Aflatoxins and OTA were extracted with organic solvents. The concentrations of aflatoxins B1, B2, G1, and G2, and OTA were measured by high-performance liquid chromatography. The values obtained were compared with the incidence of GBC in each area or country. All of the red chili peppers from the three areas showed contamination with aflatoxins below the Commission of the European Communities (EC) recommended limits ($5{\mu}g/kg$), but the OTA contamination of two samples was above the EC recommended limit ($15{\mu}g/kg$). The mean concentrations of OTA in the peppers from Chile (mean $355{\mu}g/kg$, range < $5-1,059{\mu}g/kg$) and Bolivia (mean $207{\mu}g/kg$, range $0.8-628{\mu}g/kg$), which has a high incidence of GBC, were higher than that in Peru ($14{\mu}g/kg$, range < $5-47{\mu}g/kg$), which has an intermediate GBC incidence. The OTA contamination in the red chili peppers from Chile, Bolivia, and Peru was stronger than that of aflatoxins. Our data suggest that OTA in red chili peppers may be associated with the development of GBC.

Background: Molecular testing for human papillomavirus (HPV) is the most objective and reproducible of all cervical cancer screening tests and also less demanding in terms of training and quality assurance. However, there is an impending need for cost effective molecular HPV testing methods with sampling ease, easy storage measures and minimum turn around times suitable for a low resource setting. Objective : Our aim was to evaluate the feasibility of using a fast transfer analysis (FTA) mini elute cartridge for cervical sampling to identify high risk HPV by real time PCR and to compare molecular HPV testing and Pap cytology testing to predict histologically confirmed cervical precancer (CIN 2+ lesions) in a cervical cancer prevention program. Materials and Methods: This was conducted as a pilot study (n=200) on women sampled using FTA mini elute cartridges, genotyped by two different real time PCR assays, detecting 13 high risk HPV (HR HPV) species, including HPV16 along with its physical DNA status. Results obtained from each of the tests were compared and analysed using suitable statistical tests. Results: With FTA mini elute cartridge samples HR HPV positivity was seen in 48/200 (24%). Of these, presence of HPV 16 DNA was observed in 28/48 (58.3%) women. High risk HPV was positive in 20% (37/185) of women with benign cytology and 73.3% (11/15) of women with abnormal cytology findings. A very significant correlation (${\chi}^2=22.090$ ; p=0.000) was observed between cytology and HR HPV findings showing an increasing trend of HR HPV prevalence in 50% (1/2) of LSIL, 75% (3/4) of HSIL and 100% (3/3) of SCC. Of the CIN 2+ lesions identified by histopathology, 88.9% (8/9) had HR HPV. A significant association (${\chi}^2=11.223$ ; p=0.001) of HR HPV and histopathologically confirmed CIN 2+ lesions was found. Sensitivity of the two tests were comparable but specificity of Pap testing was better (90.7% vs 70.4%) to predict histopathologically diagnosed cervical precancers. Conclusions: The current study explored the feasibility of using a FTA mini elute cartridge for cervical sampling for the first time in India as a part of a community based cervical cancer prevention program. We suggest that FTA based sampling is suitable and feasible for real time based HPV testing. Molecular HR HPV testing can be more sensitive and useful to identify high risk women requiring Pap testing which is more specific to detect histologically confirmed cervical precancer.

Background: Pancreatic cancer is the fourth leading cause of cancer related death with median survival ranging from 3 to 6 months for metastatic disease. Palliative chemotherapy has been the backbone of treatment in advanced stage and has evolved over time. Data pertaining to the disease are scarce from our part of the world where treatment poses a significant challenge due to lack of resources. Materials and Methods: A retrospective chart review was performed for all patients presenting with stage IV pancreatic carcinoma at a tertiary care hospital in Karachi, Pakistan between January 2008 and December 2012. Data were collected using a pre-designed, coded questionnaire looking at patient characteristics, treatment given and outcome. Results: 101 patients were found to be eligible. Mean age was $56.7{\pm}12.8years$, the male to female ratio was 2:1 and most patients had a good performance status. More than half of the tumors were located in the head (57%, n=58) and almost all were adenocarcinomas (95%, n=96). Some 58% (n=59) received first line chemotherapy of which 49% (n=29) received gemcitabine-based regimens and 39% (n=23) received FOLFIRINOX. The median progression free survival for gemcitabine based treatment was 2.9 months (IQR=1.6-5.6) as opposed to 7.3 months (IQR=4.5-9.2) for FOLFIRINOX (P=0.02). Median overall survival was 4.9 months (IQR=2.3-9.5) for first line gemcitabine based treatment and 10.5 months (IQR=7.0-13.2) for first line FOLFIRINOX therapy (P=0.002). Patients on FOLFIRINOX had better survival across all subgroups. Inpatient admissions and dose reductions were more frequent with FOLFIRINOX but the difference between the two regimens was not statistically significant. FOLFIRINOX could be successfully administered as outpatient therapy to a number of patients. Conclusions: FOLFIRINOX remains a suitable first line option in patients with metastatic pancreatic cancer with good performance status even in a resource-poor country where diagnostic and supportive care facilities may be less than optimal and cost is a limitation.

Background: Chronic lymphoid leukemia (CLL) is a malignant hematopoietic disorder, the most common of all adult leukemias with a distinctive immunophenotype. It is well established that CLL patients can have autoimmune complications, amongst them autoimmune hemolytic anemia as the most frequent. This study was carried out to determine the frequency of direct Coombs Test positivity in CLL patients and its possible correlation with Rai staging, hematological parameters and biochemical markers. Materials and Methods: This descriptive cross sectional study was carried at Liaquat National Hospital from January 2011 to June 2013. Sixty untreated patients with B- chronic lymphoid leukemia were enrolled. Complete blood count, direct Coombs test, serum urea, creatinine, uric acid and LDH levels were determined. Data were compiled and analyzed using SPSS version 21. Results: Out of 60 patients, 42(70%) were males and 18(30%) were females. Mean age was $59{\pm}9.2years$. Male to female ratio was 2.1: 1. The frequency of direct antiglobulin test (DAT) positivity was found to be 23.3%. The monospecific IgG was positive in 11 patients (18.3%); C3d positivity was evident in 1 patient (1.6%) and 2 patients (3.3%) had dual IgG and C3d positivity. The mean hemoglobin was $10.8{\pm}2.4gm/dl$. Significantly low mean hemoglobin of $8.3{\pm}3.0gm/dl$ was seen in Coombs positive patients compared with negative patients having a mean hemoglobin level of $11.7{\pm}1.6gm/dl$ (P<0.001). DAT positivity also demonstrated a positive association with advanced Rai stage III disease (P<0.01). No associations were noted with age, gender and biochemical markers. Conclusions: Direct Coombs test positivity in CLL in our patients, unlike in Western studies, appears relatively high, indicating significant autoimmune hemolytic anemia and advanced Rai stage in our setting. DAT positivity can be considered as a surrogative marker for advanced clinical disease.

Purpose: To investigate the efficacy and safety of selective radiotherapy after distant metastasis of nasopharyngeal carcinoma (NPC) treated with dose-dense cisplatin plus fluorouracil. Materials and Methods: Eligible patients were randomly assigned to a study group treated with dose-dense cisplatin plus fluorouracil following selective radiotherapy and a control group receiving traditional cisplatin plus fluorouracil following selective radiotherapy according to a 1:1 distribution using a digital random table method. The primary endpoint was overall survival (OS). Secondary endpoints were progression-free survival (PFS), objective response rate, relapse or progression rate in the radiation field and treatment toxicity. Results: Of 52 patients in the study group, 20 cases underwent radiotherapy., while in the control group of 51 patients, 16 underwent radiotherapy. The median PFS, median OS, survival rates in 1, 2 and 3 years in study and control group were 20.9 vs 12.7months, 28.3 vs 18.8months, 85.2%vs 65.9%, 62.2% vs 18.3%, and 36.6%vs 5.2% (p values of 0.00, 0.00, 0.04, 0.00 and 0.00, respectively). Subgroup analysis showed that the median OS and survival rates of 1, 2, 3 years for patients undergoing radiotherapy in the study group better than that in control group( 43.2vs24.1 months, 94.1% vs 86.7%, 82.4% vs 43.3%, 64.7% vs 17.3%, (p=0.00, 0.57, 0.04 and 0.01, respectively). The complete response rate, objective response rate after chemotherapy and three months after radiotherapy, relapse or progression rate in radiation field in study group and in control group were 19.2% vs 3.9%, 86.5% vs 56.9%, 85% vs 50%, 95% vs 81.3% and 41.3% vs 66.7% (p =0.03, 0.00, 0.03,0.30, 0.01 respectively). The grade 3-4 acute adverse reactions in the study group were significantly higher than in the control group (53.8% vs 9.8%, p=0.00). Conclusions: The survival of patients benefits from selective radiotherapy after distant metastasis of NPC treated with dose-dense cisplatin plus fluorouracil.

Background: The aim of this study was to assess the relationship between IL-18 gene polymorphisms and HBV-related diseases and whether these polymorphisms influence its expression in the Guangxi Zhuang population. Materials and Methods: We enrolled 129 chronic HBV infected (CHB) patients, 86 HBV-related liver cirrhosis (LC) patients and 160 healthy controls in our study. Polymerase chain reaction-restriction fragment length polymorphism methods were used to detect IL-18 gene -607C/A, -137G/C polymorphisms, and an ELISA kit was employed to determine serum IL-18 levels. Results: No correlation was found between the -607C/A polymorphism and risk of HBV-related disease. For the -137G/C polymorphism, the GC genotype and C allele were associated with a significantly lower risk of CHB (95%CI: 0.32-0.95, p=0.034 and 95%CI: 0.35-0.91, p=0.018) and HBV-related LC (95%CI: 0.24-0.89, p=0.022 and 95%CI: 0.28-0.90, p=0.021). A similar decreased risk was also found with the A-607C-137 haplotype. With respect to IL-18 expression, it was significantly lower in both patient groups, but no association was noted between the two polymorphisms in the IL-18 gene and its expression. Conclusions: Our study indicated that the -137C allele in the IL-18 gene may be a protective factor for HBV-related disease, and serum IL-18 level may be inversely associated with CHB and HBV-related LC.

Background: Polymorphisms of genes encoding PSCA, PLCE1 and MUC1 have been associated with the risk of different cancers in genome wide association studies (GWAS). Up to date there are limited data on the role of these genetic alterations in colorectal cancer (CRC) development. The aim of this study was to evaluate potential associations between single nucleotide polymorphisms (SNPs) of genes encoding PSCA, PLCE1 and MUC1 and the presence of CRC in European populations. Materials and Methods: Gene polymorphisms were analyzed in 574 European subjects (controls: n=382; CRC: n=192). PSCA C>T (rs2294008), PSCA G>A (rs2976392), MUC1 A>G (rs4072037) and PLCE1 A>G (rs2274223) SNPs were genotyped by RT-PCR. Results: The distribution of genotypes for all four SNPs was in line with the Hardy-Weinberg equilibrium (rs2294008, P=0.153; rs2976392, P=0.269; rs4072037, P=0.609; rs2274223, P=0.858). The distribution of genotypes and alleles of PSCA C>T, PSCA G>A, MUC1 A>G and PLCE1 A>G SNPs was similar among controls and CRC patient groups (P>0.05). GG genotype of MUC1 SNP was more frequent in CRC patients (24.0%) than in controls (20.2%); however, this association failed to reach significance (OR-1.45, P=0.15). Overall, in the present study SNPs of PSCA (rs2294008, rs2976392), MUC1 (rs4072037) and PLCE1 (rs2274223) genes were not associated with the presence of CRC. Conclusions: Gene polymorphisms of PSCA, PLCE1 and MUC1 genes are not associated with the presence of CRC in European subjects.

Background: Experience of lung cancer includes negative impacts on both physical and psychological health. Pain is one of the negative experiences of lung cancer. Cognitive behavioral therapy techniques are often recommended as treatments for lung cancer pain. The objective of this review was to synthesize the evidence on the effectiveness of cognitive behavioral therapy techniques in treating lung cancer pain. This review considered studies that included lung cancer patients who were required to 1) be at least 18 years old; 2) speak and read English or Thai; 3) have a life expectancy of at least two months; 4) experience daily cancer pain requiring an opioid medication; 5) have a positive response to opioid medication; 6) have "average or usual" pain between 4 and 7 on a scale of 0-10 for the day before the clinic visit or for a typical day; and 7) able to participate in a pain evaluation and treatment program. This review considered studies to examine interventions for use in treatment of pain in lung cancer patients, including: biofeedback, cognitive/attentional distraction, imagery, hypnosis, and meditation. Any randomized controlled trials (RCTs) that examined cognitive behavioral therapy techniques for pain specifically in lung cancer patients were included. In the absence of RCTs, quasi-experimental designs were reviewed for possible conclusion in a narrative summary. Outcome measures were pain intensity before and after cognitive behavioural therapy techniques. The search strategy aimed to find both published and unpublished literature. A three-step search was utilised by using identified keywords and text term. An initial limited search of MEDLINE and CINAHL was undertaken followed by analysis of the text words contained in the title and abstract, and of the index terms used to describe the article. A second search using all the identified keywords and index terms was then undertaken across all included databases. Thirdly, the reference list of all identified reports and articles were searched for additional studies. Searches were conducted during January 1991- March 2014 limited to English and Thai languages with no date restriction. Materials and Methods: All studies that met the inclusion criteria were assessed for methodological quality by three reviewers using a standardized critical appraisal tool from the Joanna Briggs Institute (JBI). Three reviewers extracted data independently, using a standardized data extraction tool from the Joanna Briggs Institute (JBI). Ideally for quantitative data meta-analysis was to be conducted where all results were subject to double data entry. Odds ratios (for categorical data) and weighted mean differences (for continuous data) and their 95% confidence intervals were to be calculated for analysis and heterogeneity was to be assessed using the standard Chi-square. Where statistical pooling was not possible the finding were be presented in narrative form. Results: There were no studies located that met the inclusion requirements of this review. There were also no text and opinion pieces that were specific to cognitive behavioral therapy techniques pain and lung cancer patients.Conclusions: There is currently no evidence available to determine the effectiveness of cognitive behavioural therapy techniques for pain in lung cancer patients.

Aims: To investigate effect of metallic nanoparticles, silver (AgNPs) and gold nanoparticles (AuNPs) as antitumor treatment in vitro against human breast cancer cells (MCF-7) and their associated mechanisms. This could provide new class of engineered nanoparticles with desired physicochemical properties and may present newer approaches for therapeutic modalities to breast cancer in women. Materials and Methods: A human breast cancer cell line (MCF-7) was used as a model of cells. Metallic nanoparticles were characterized using UV-visible spectra and transmission electron microscopy (TEM). Cytotoxic effects of metallic nanoparticles on MCF-7 cells were followed by colorimetric SRB cell viability assays, microscopy, and cellular uptake. Nature of cell death was further investigated by DNA analysis and flow cytometry. Results: Treatment of MCF-7 with different concentrations of 5-10nm diameter of AgNPs inhibited cell viability in a dose-dependent manner, with IC50 value of $6.28{\mu}M$, whereas treatment of MCF-7 with different concentrations of 13-15nm diameter of AuNPs inhibited cell viability in a dose-dependent manner, with IC50 value of $14.48{\mu}M$. Treatment of cells with a IC50 concentration of AgNPs generated progressive accumulation of cells in the S phase of the cell cycle and prevented entry into the M phase. The treatment of cells with IC50 concentrations of AuNPs similarly generated progressive accumulation of cells in sub-G1 and S phase, and inhibited the entrance of cells into the M phase of the cell cycle. DNA fragmentation, as demonstrated by electrophoresis, indicated induction of apoptosis. Conclusions: Our engineered silver nanoparticles effectively inhibit the proliferation of human breast carcinoma cell line MCF-7 in vitro at high concentration ($1000{\mu}M$) through apoptotic mechanisms, and may be a beneficial agent against human carcinoma but further detailed study is still needed.

Background: Hepatocellular carcinoma is one of the most common cancers worldwide. Its prevalence is increasing in many countries. Plant products can be used to protect against cancer due to natural anticancer and chemopreventive constituents. Strobilanthes crispus is one of plants with potential chemopreventive ability. Objective: This study aimed to evaluate the anticancer effects of Strobilanthes crispus juice on hepatocellular carcinoma cells. Materials and Methods: MTT assays, flow cytometry, comet assays and the reverse transcription-polymerase chain reaction (RT-PCR) were used to determine the effects of juice on DNA damage and cancer cell numbers. Results: This juice induced apoptosis after exposure of the HepG2 cell line for 72 h. High percentages of apoptotic cell death and DNA damage were seen at the juice concentrations above 0.1%. It was found that the juice was not toxic for normal cells. In addition, juice exposure increased the expression level of c-myc gene and reduced the expression level of c-fos and c-erbB2 genes in HepG2 cells. The cytotoxic effects of juice on abnormal cells were in dose dependent. Conclusions: It was concluded that the Strobilanthes crispus juice may have chemopreventive effects on hepatocellular carcinoma cells.

Background: Medication policy development in Thailand is continually promoting rational drug use. Letrozole, an endocrine therapy drug, is usually prescribed for post-menopausal status early and advanced stage breast cancer. After Ministry of Public Health announced Letrozole as compulsory licensed drug in 2009, more breast cancer patients can access to this drug at low cost especially those within universal coverage schemes. To ensure that Letrozole is rationally prescribed, the drug utilization study was conducted. Objectives: The aim of this study was to describe the appropriate use of Letrozole in breast cancer and the relationship between appropriate use and health benefit schemes. Materials and Methods: A retrospective study to evaluate use of Letrozole in breast cancer patients was performed for six months between January - June 2010 in seven regional cancer hospitals, Thailand. All prescriptions of Letrozole were identified from pharmacy dispensing databases and prescription papers. A medical record review was also performed to evaluate appropriate use referring to the drug use evaluation criteria. The approved criterion of this study was referred from the guideline of Thai National Formulary version 2010. Results: There were 681 prescriptions of Letrozole for 254 breast cancer patients with an average age of $58.6{\pm}10.0years$. The patients in universal coverage scheme (UCS), civil servant medication benefit scheme (CSMBS) and social security scheme (SSS) were 77.7%, 18.5% and 8.7% respectively. 10.6% were prescribed Letrozole for the first time. Letrozole were prescribed by oncologists (82.8%). The average number of tablets per prescription was $58{\pm}10$. Calcium supplements were prescribed concomitant with Letrozole for 19.4%. To assess drug use evaluation criteria, 45 prescriptions were excluded because of uncompleted clinical data, 636 prescriptions were evaluated. The study showed 86 prescriptions (13.5%) with inappropriate use including 6 (0.9%) not prescribed for estrogen receptor (ER) and/or progesterone receptor (PR) positive, 31 (4.9%) not prescribed for post-menopausal and 49 (7.7%) not prescribed for an appropriate duration. Appropriate use percentages in different health benefit schemes were similar, 85.7% of CSMBS, 86.4% of SSS and 86.7% of UCS. The relationship between health benefit scheme and appropriate use of Letrozole was not significantly different, ${\chi}^2$ (2, N = 636) = 0.081, p > 0.05. Conclusions: The study showed inappropriate use in breast cancer patients because of non-compliance with duration, menopausal status and hormone receptor requirements. To prescribe appropriate indication did not referred to the appropriate practice along the treatment. Drug use evaluation proved very useful for detecting the sign of inappropriate use and allows immediate feedback to the stakeholder for developing medication policy in the future. Importantly, there was no significantly difference in appropriate use of Letrozole across health benefit schemes.

Methotrexate (Mtx), used for its anticancer and immunsuppresive properties, is known to be a nephrotoxic agent. We aimed to investigate the effects of lycopene (Lyc) alone or combined with melatonin (Mel) on Mtxinduced nephrotoxicity since both of these agents have antioxidant and anti-inflammatory effects. Nephrotoxicity was induced by intraperitoneal administration of methotrexate at a dose of 20 mg/kg. Treatment both with Lyc alone and Lyc combined with Mel provided significant reduction in tumor necrosis factor-alpha, interleukin 1-beta and ceruloplasmin levels in Mtx administered rats. Hovewer, Lyc combined with Mel provided a significant reduction also in NO levels. Hstopathological examination showed that there was an obvious improvement in the degenerative changes compared to Mtx administrated group with the Lyc combined Mel group giving best protection. In conclusion Lyc alone and combined with Mel provided significant improvement against renal damage caused by Mtx, preseumably via antioxidant and anti-inflammatory activities.

Background: Gastric cancer accounts for about 8% of the total cancer cases and 10% of total cancer deaths worldwide. It is the second lethal cancer after esophageal cancer and is considered the fourth most common cancer in north and northwest Iran. The bcl2 family has a key role in the regulation of apoptosis and change in its expression can contribute to cancer. This study initially scheduled to determine the expression of bcl2 gene in tissue samples of adenocarcinoma cancer patients. Materials and Methods: A total of 10 samples of gastric adenocarcinoma and 10 of normal tissues from Sari hospital were selected and after DNA extraction from tissues, bcl2 gene expression assayed by real-time PCR. Results: Our results demonstrated higher expression of the bcl2 gene in control compared with cancer and marginal cancer tissues. Conclusions: On one hand BCL2 plays an important role as an oncogene to inhibit apoptosis; on the other hand, it can initiate cell cycle arrest at G0 stage. Our observed association between its expression and patient survival is quite conflicting and may be tissue-specific. The data suggest expression both tumoural and non-tumoral(marginal) groups have lowered expression than controls (P>0.05). Due to the low number of samples we could not examine the relationship with clinicopathological features. However, bcl-2 expression may be important for prognostic outcome or a useful target for therapeutic intervention.

Background: Melanoma differentiation-associated gene-7 (MDA-7)/interleukin-24 (IL-24), a unique tumor suppressor gene, has killing activity in a broad spectrum of cancer cells. Herein, plasmids producing mda-7 proteins fused to different RGD peptides (full RGD4C and shortened RGD, tRGD) were evaluated for apoptosis induction with a hepatocellular carcinoma cell line, Hep-G2. The study aim was to improve the apoptosis potency of mda-7 by tethering to RGD peptides. Materials and Methods: Three plasmids including mda-7, mda-7-RGD and mda-7-tRGD genes beside a control vector were transfected into Hep-G2 cells. After 72 hours incubation, cell viability was evaluated by MTT assay. In addition, the rate of apoptosis was analyzed by flow cytometry using PI/annexin staining. To detect early events in apoptosis, 18 hours after transfection, expression of the BAX gene was quantified by real time PCR. Modeling of proteins was also performed to extrapolate possible consequences of RGD modification on their structures and subsequent attachment to receptors. Results and Conclusions: In MTT assays, while all mda-7 forms showed measurable inhibition of proliferation, unmodified mda-7 protein exhibited most significant effect compared to control plasmid (P<0.001). Again, flow cytometry analysis showed a significant apoptosis induction by simple mda-7 gene but not for those RGD-fused mda-7 proteins. These findings were also supported by expression analysis of BAX gene (P<0.001). Protein modelling analysis revealed that tethering RGD at the end of IL-24/Mda7 disrupt attachment to cognate receptor, IL-20R1/IL-20R2. In conclusion, fusion of RGD4C and shortened RGD peptides to carboxyl terminal of mda7, not only reduce apoptosis property in vitro but also disrupt receptor attachment as demonstrated by protein modelling.

Purpose: This study aimed to investigate the incidence and mortality of breast cancer, and its relationship with human development index (HDI) and its components in Asia in 2012. Materials and Methods: This study was an ecologic study in Asia for assessment of the correlation between age-specific incidence rate (ASIR) and age-specific mortality rate (ASMR) with HDI and its details that include: life expectancy at birth, mean years of schooling and gross national income (GNI) per capita. Data about SIR and SMR for every Asian country for the year 2012 were obtained from the global cancer project. We used a bivariate method for assessment of the correlation between SIR and SMR and HDI and its individual components. Statistical significance was assumed if P<0.05. All reported P-values are two-sided. Statistical analyses were performed using SPSS (Version 15.0, SPSS Inc.). Results: In 2012, 639,824 cases of breast cancer were recorded in Asian countries. Countries with the highest standardized incidence rate (ASIR) (per 100,000) were Israel (80.5), Lebanon (78.7), Armenia (74.1) and the highest standard mortality rate (ASMR) was observed in Pakistan (25.2), Armenia (24.2), and Lebanon (24). There was a positive correlation between the ASIR of breast cancer and HDI (r = 0.556, p <0.001), whereas there was a negative correlation between the ASMR of breast cancer and HDI (r = -0.051). Conclusions: Breast cancer incidence in countries with higher development is greater, while mortality is greatest in countries with less development. There was a positive and significant relationship between the ASIR of breast cancer and HDI and its components. Also there was a negative but non significant relationship between the ASMR of breast cancer and HDI.

Background: The prevalence of metronidazole-resistant H. pylori is almost 50% in Thailand which severely limits the use of this drug for eradication therapy. The aims of this study were to evaluate the efficacy and safety profiles of 7-day bismuth-based quadruple therapy including metronidazole as an initial treatment for H. pylori infection in a high metronidazole resistance area. Materials and Methods: This study was performed at Thammasat University Hospital and King Chulalongkorn Memorial Hospital during January 2009 to October 2010. Patients with non-ulcer dyspepsia (NUD) with active H. pylori infection were assigned to receive seven days of quadruple therapy (pantoprazole 40 mg bid, bismuth subsalicylate 1,048 mg bid, amoxicillin 1 gm bid and metronidazole 400 mg tid). H. pylori infection was defined as positive H. pylori culture or two positive tests (rapid urease test and histology). Antibiotic susceptibility test for metronidazole by Epsilometer test (E-test) was performed in all positive cultures. At least four weeks after treatment, $^{13}C$ urea breath test ($^{13}C-UBT$) was performed to confirm H. pylori eradication. Results: A total of 114 patients were enrolled in this study, 50 males and 64 females with a mean age of 49.8 years. All 114 patients had a diagnosis of NUD. Overall eradication as confirmed by negative $^{13}C-UBT$ was achieved in 94 out of 114 patients (82.5%). 44 patients had positive cultures and success for E-test. In vitro metronidazole resistance was observed in 22/44 (50%) patients. Eradication rate in patients with metronidazole resistant strains was 16/22 (72.7%) and 20/22 (90.1%) with metronidazole sensitive strains (72.7% vs 90.1%, p-value=0.12; OR=3.75 [95%CI=0.6-31.5]). Minor adverse reactions included nausea, bitter taste, diarrhea and black stools but none of the patients dropped out from the study. Conclusions: Initial treatment with 7-day bismuth-based quadruple therapy including metronidazole, amoxycillin and pantoprazole is highly effective and well tolerated for metronidazole-sensitive H. pylori infections. However, the efficacy markedly decline with metronidazole resistance. Longer duration of this regimen might be required to improve the eradication rate and larger multi-center studies are needed to confirm this hypothesis.

Background: HPV DNA testing has been recently introduced as an adjunct test to cytology in the follow-up of patients after treatment for cervical lesions using the loop electrosurgical excision procedure (LEEP). The aim of this study was to evaluate the role of HPV testing in the detection of persistent or recurrent disease after LEEP in patients with cervical epithelial lesions in northern Thailand. Materials and Methods: Patients who underwent LEEP as a treatment for histological low-grade (LSIL) or high-grade squamous intraepithelial lesion (HSIL) or worse at Chiang Mai University Hospital between June 2010 and May 2012 were included. Follow-ups were scheduled at 6-month intervals and continued for 2 years using co-testing (liquid-based cytology and Hybrid Capture 2 [HC2]) at 6 months and 24 months and liquid-based cytology alone at 12 and 18 months. Results: Of 98 patients included, the histological diagnoses for LEEP included LSIL in 16 patients, and HSIL or worse in 82 patients. The LEEP margin status was negative in 84 patients (85.7%). At follow-up, 10 patients (10.2%) had persistent/recurrent lesions; 4 among LSIL patients (25.0%) and 6 in the group with HSIL or worse (7.3%). Only 2 of 82 patients (2.4%) with HSIL or worse diagnoses had histological HSIL in the persistent/recurrent lesions. Using histologically confirmed LSIL as the threshold for the detection of persistent/recurrent disease, cytology had a higher sensitivity than HC2 (90.0% versus 70.0%). At the 6-month follow-up appointment, combined cytology and HC2 (co-testing) had a higher sensitivity in predicting persistent/recurrent disease (80.0%) compared with that of cytology alone (70.0%) and HC2 (50.0%). Conclusions: After LEEP with a negative surgical margin, the rate of persistent/recurrent lesions is low. The addition of HPV testing at the 6-month visit to the usual cytology schedule may be an effective approach in the follow-up after LEEP.

Background: Previous studies investigating the association between miR-34b/c rs4938723 polymorphism and cancer risk showed inconclusive. Here, we performed meta-analysis to investigate the association between miR- 34b/c rs4938723 polymorphism and digestive cancer risk. Materials and Methods: Literature database including PubMed, OVID, Chinese National Knowledge Infrastructure (CNKI) were searched for publications concerning the association between the miR-34b/c rs4938723 polymorphism and digestive cancer risk. Results: A total of 6 studies consisting of 3246 cases and 3568 controls were included in this meta-analysis. The combined analysis suggested the miR-34b/c rs4938723 polymorphism significantly reduced digestive cancer risk under allelic model, homogeneous co-dominant model and recessive model (C vs T: OR=0.88, 95%CI=0.82-0.95, p-value=0.001; CC vs TT: OR =0.67, 95%CI=0.57-0.80, p-value=0.000; CC vs TT/TC: OR=0.68, 95%CI=0.58-0.80, p-value=0.000). Q-test and I2 test revealed no significant heterogeneity in all genotype comparisons. The Begger's funnel plot and Egger's test did not show significant publication bias. Conclusions: The current evidence supports the conclusion that the miR-34b/c rs4938723 polymorphism decreases an individual's susceptibility to digestive cancers.

Background: Colorectal cancer (CRC) is one of the most common cancers worldwide. This study aimed to investigate the risk factors for colorectal cancer in the Thai population. Materials and Methods: A cohort study was carried out in Khon Kaen, Thailand, including 71 cases of histologically confirmed CRC patients among 19,861 participants, aged 30-69 years, who were recruited for a cohort study during the period 1990-2001. Participants were followed-up until 31 December, 2013. To identify factors associated with the incidence of colorectal cancer, hazard ratios were evaluated using Cox proportional hazard regression. Results: No environmental variables could be shown to be significantly related to the risk of CRC. Although in our sample, CRC was more prevalent among males, ex-smokers, and those who drank alcohol beverages ${\geq}50gram/day$, but we could not demonstrate significantly associations (HRmale= 1.67, 95% CI, 0.80-3.49, HR ex-smokers = 1.34, 95% CI, 0.52-3.46, and HRalc ${\geq}50=1.08$, 95% CI, 0.43-2.71). Individuals within the sample with a family history of cancer, working hour >8 hours per day, and current-smokers appeared to have decrease risk of CRC, but again these relationship could not be shown to be significantly associated (HRfam cancer= 0.96, 95% CI, 0.85-1.09, HRwork>8= 0.84, 95% CI, 0.36-1.93, and HRcurrent-smoker = 0.51, 95% CI, 0.18-1.38). Conclusions: We found no evidence of environmental factors effecting the risk of CRC. There is a need for further research to determine why factors identified risk in other populations appear to not be associated with CRC risk in Thais.

Background: Stomach cancer is one of leading causes of death worldwide. In Thailand, the incidence and mortality of stomach cancer are in the top ten for cancers. Effects of DNA repair gene X-ray repair cross complementary protein 1 (XRCC1) polymorphisms and clinicopathological characteristics on survival of stomach cancer in Thailand have not been previously reported. The aim of this study was to investigate the effects of XRCC1 gene and clinicopathological characteristics on survival of stomach cancer patients in Thailand. Materials and Methods: Data and blood samples were collected from 101 newly diagnosed stomach cancer cases pathologically confirmed and recruited during 2002 to 2006 and followed-up for vital status until 31 October 2012. Genotype analysis was performed using real-time PCR-HRM. The data were analyzed using the Kaplan-Meier method to yield cumulative survival curve, log-rank test to assess statistical difference of survival and Cox proportional hazard models to estimate adjusted hazard ratio. Results: The total followed-up times were 2,070 person-months, and the mortality rate was 4.3 per 100 person-months. The median survival time after diagnosis was 8.07 months. The cumulative 1-, 3-, 5-years survival rates were 40.4%, 15.2 % and 10.1 % respectively. After adjustment, tumour stage were associated with an increased risk of death (p= 0.036). The XRCC1 Gln339Arg, Arg/Arg homozygote was also associated with increased risk but statistically this was non-significant. Conclusions: In addition to tumour stage, which is an important prognostic factor affecting to the survival of stomach cancer patients, the genetic variant Gln339Arg in XRCC1 may non-significantly contribute to risk of stomach cancer death among Thai people. Larger studies with different populations are need to verify ours findings.

Background: Most northeast Thai vegetables may play roles in human health by acting as antioxidant and anticancer agents. Recent study showed that Cratoxylum formosum subsp. pruniflorum (Kurz.) Gogel. (Teawdang) could inhibit growth of liver cancer cell lines. Cervical cancer, which has human papilloma virus as its main cause, is found at high incidence in Thailand. Due to increasing drug resistance, searches for potential anticancer compounds from natural source are required. Therefore, our purpose was to evaluate the cytotoxicity of Teawdang extracts in cervical cancer cell lines. Materials and Methods: Teawdang edible parts, purchased from Khon Kaen market during July-October 2013 was extracted with organic solvent. Phenolic profiles of crude hexane (CHE), ethyl acetate (CEE), methanol (CME) and water (CWE) extracts were performed by high performance liquid chromatographic (HPLC) techniques. Their cytotoxic effects on cervical cancer cells were investigated with HPV-non infected (C-33A) and HPV-infected (HeLa and SiHa) cell lines. Results: HPLC profiles showed that all crude extracts contained caffeine, ferulic acid and resveratrol. CME and CEE had high contents of gallic acid and quercetin. Catechin was found only in CWE. Cytotoxicity test showed that CEE had the lowest IC50 on HeLa ($143.18{\pm}13.35 {\mu}g/mL$) and SiHa cells ($106.45{\pm}15.73{\mu}g/mL$). C-33A cells were inhibited by CWE ($IC50=130.95{\pm}3.83{\mu}g/mL$). Conclusions: There were several phenolic compounds in Teawdang extracts which may have cytotoxic effects on cervical cancer cell lines. Investigation of these bioactive compounds as new sources of anticancer agents is recommended.

Background: The aim of this study was to analyze the prognostic implications of pretreatment circulating endothelial cells (CECs) and circulating endothelial progenitor cells (CEPCs) for the survival of patients with lung cancer. Materials and Methods: Relevant literature was identified using Medline and EMBASE. Patient clinical characteristics, overall survival (OS) and progression-free survival (PFS) together with CEC and CEPC positive rates before treatment were extracted. STATA 12.0 was used for our analysis and assessment of publication bias. Results: A total of 13 articles (8 for CEC and 5 for CEPC, n=595 and n=244) were pooled for the global meta-analysis. The odds ratio (OR) for OS predicted by pretreatment CECs was 1.641 [0.967, 2.786], while the OR for PFS was 1.168 [0.649, 2.100]. The OR for OS predicted by pretreatment CEPCs was 12.673 [5.274, 30.450], while the OR for PFS was 4.930 [0.931, 26.096]. Subgroup analyses were conducted according to clinical staging. Odds ratio (OR) showed the high level of pretreatment CECs only correlated with the OS of patients with advanced lung cancer (stage III-IV). Conclusions: High counts of CECs seem to be associated only with worse 1-year OS in patients with lung cancer, while high level of pretreatment CEPCs correlate with both worse PFS and OS.

miR-129-2 is frequently downregulated in multiple cancers. However, how it is silenced in cancers remains unclear. Here we investigated the expression profile and potential biological function of miR-129-2 in glioblastoma (GBM), the most common and lethal form of brain tumors in adults. We showed that miR-129-2 is lost in GBM patient specimens and cultured cell lines. miR-129-2 expression could be restored upon treatment with a histone deadetylase inhibitor (trichostatin A) but not a DNA methylation inhibitor (5-Aza-2'-deoxycytidine), and more profound effect was observed with the treatment of these two drugs in combination. Furthermore, forced expression of miR-129-2 repressed the expression of major oncogenic genes such as PDGFRa and Foxp1 in GBMs. Consistently, expression of miR-129-2 significantly inhibits GBM cell proliferation in vitro. These results reveal that miR-129-2 is epigenetically regulated and functions as a tumor suppressor gene in GBMs, suggesting it may serve as a potential therapeutic target for GBM treatment.

Background: The aim of this meta-analysis was to assess the efficacy of the apparent diffusion coefficient (ADC) value of diffusion-weighted MRI (DWI) for differentiating biliary tract cancer (BTC) from benign biliary tract diseases in Asians. Materials and Methods: We systematically searched Embase and PubMed prior to December 2014. Eight studies conducted in Asians met our predetermined inclusion criteria. Results: Our meta-analysis results showed that ADC values in BTC tissues were significantly lower than in benign biliary tract tissues (SMD = -1.54, 95%CI: -1.75~-1.33, P<0.001). Subgroup analysis based on the MRI machine type showed that the ADC values were consistent, accurate and reliable in the diagnosis of BTC when comparing cancer tissue vs. benign tissue under the Siemens 1.5 T/3.0 T, Philips 1.5 T/3.0 T, GE 1.5 T, and Toshiba 1.5 T types, respectively (all P<0.05). Further, ADC values were still consistent and accurate in the differential diagnosis of BTC under the b value of 800 and $1000s/mm^2$ (all P<0.05). Conclusions: Our findings supported potential clinical applications of DWI ADC values in differentiating BTC from benign biliary tract diseases in Asians.

Background: Cancer is a leading cause of death worldwide. A large proportion of cancer deaths are preventable through early detection but there are a range of social, emotional, cultural and financial dimensions that hinder the effectiveness of cancer prevention and treatment efforts. Cancer stigma is one such barrier and is increasingly recognized as an important factor influencing health awareness and promotion, and hence, disease prevention and control. The impact and extent of stigma on the cancer early detection and care continuum is poorly understood in India. Objectives: To evaluate cancer awareness and stigma from multiple stakeholder perspectives in North India, including men and women from the general population, health care professionals and educators, and cancer survivors. Materials and Methods: A qualitative study was conducted with in-depth interviews (IDIs) and focus group discussions (FGDs) among 39 individuals over a period of 3 months in 2014. Three groups of participants were chosen purposively - 1) men and women who attended cancer screening camps held by the Indian Cancer Society, Delhi; 2) health care providers and 3) cancer survivors. Results: Most participants were unaware of what cancers are in general, their causes and ways of prevention. Attitudes of families towards cancer patients were observed to be positive and caring. Nevertheless, stigma and its impact emerged as a cross cutting theme across all groups. Cost of treatment, lack of awarenes and beliefs in alternate medicines were identified as some of the major barriers to seeking care. Conclusions: This study suggests a need for spreading awareness, knowledge about cancers and assessing associated impact among the people. Also Future research is recommended to help eradicate stigma from the society and reduce cancer-related stigma in the Indian context.

Background: There is no suggested molecular indicator for the determination of which patients will benefit from anti-angiogenetic treatment in metastatic colorectal cancers. Materials and Methods: In this study, VEGF and $HIF-1{\alpha}$ expression and their clinical significance were studied in tumor tissues of patients with colorectal cancer receiving bevacizumab-based treatment. VEGF and $HIF-1{\alpha}$ were assessed by immunohistochemistry in the primary tumors of 53 metastatic colorectal cancer patients receiving chemotherapy in combination with first line bevacizumab. Results: The clinical benefit rate in the low-VEGF expression group was 38%, while it was 62% in the high expression group. While the median progression-free survival (PFS) was 10 months in the high-VEGF expression group, it was 8 months in the low-VEGF expression group (p = 0.009). The median overall survival (OS) was found to be 26 months vs 15 months. Thus, when VEGF was strongly expressed it was in favor of that group and the difference was statistically significant (p = 0.03). High VEGF expression rate was an independent factor that correlated with OS or PFS (p=0.016 and 0.009, respectively). Conclusions: The data showed that VEGF may have predictive value for determining the treatment of CRC.

Background: The human leukocyte antigen-G (HLA-G) gene is highly expressed in cancer pathologies and is one strategy used by tumor cells to escape immune surveillance. A 14-bp insertion/deletion (InDel) polymorphism of the HLA-G gene has been suggested to be associated with HLA-G mRNA stability and the expression of HLA-G. The aim of present study was to assess any genetic association between this polymorphism and breast cancer among Iranian-Azeri women. Materials and Methods: In this study 227 women affected with breast cancer, in addition to 255 age-sex and ethnically matched healthy individuals as the control group, participated. Genotyping was performed using polymerase chain reaction and electrophoresis assays. The data were compiled according to the genotype and allele frequencies, compared using the Chi-square test. Statistical significance was set at P<0.05. Results: In this case-control study, no significant difference was found between the case and control groups at allelic and genotype levels, although there is a slightly higher allele frequency of HLA-G 14bp deletion in breast cancer affected group. However,when the stage I subgroup was compared with stage II plus stage III subgroup of affected breast cancer, a significant difference was seen with the 14 bp deletion allele frequency. The stage II-III subgroup patients had higher frequency of deletion allele (57.4% vs 45.8%) than stage I cases (${\chi}^2=4.16$, p-value=0.041). Conclusions: Our data support a possible action of HLA-G 14bp InDel polymorphism as a potential genetic risk factor for progression of breast cancer. This finding highlights the necessity of future studies of this gene to establish the exact role of HLA-G in progression steps of breast cancer.

Purpose: To evaluate efficacy of transarterial chemoembolization (TACE) combined with radiofrequency ablation (RFA) in treatment of patients with hepatocellular carcinoma. Materials and Methods: During January 2009 to March 2012, 80 patients with hepatocellular carcinoma underwent TACE, with or without RFA. Alfafetoprotein (AFP) was checked before and after procedure. CT scans were obtained one month after TACE or RFA for all patients to evaluate tumor changes. Complete response+partial response+stable disease (CR+PR+SD)/n were used to assess the disease control rate (DCR). Survival at 3, 6 and 12 months was compared in both groups. Results: AFP levels in TACE + RFA group dropped rapidly, becoming obviously lower than that of the TACE group. In the TACE + RFA group DCR was 93.8%, while only 76.8% in the TACE group. The treatment effect between the two groups was statistically significant (P<0.05) by Ridit analysis. 1 year survival rate in the TACE + RFA group was 92.5%, significantly higher than that of the TACE group at 77.5% (P<0.05). Conclusions: TACE and RFA as combined therapy method for patients with middle and terminal stage HCC gives full play to synergy between the two and improves the therapeutic effect.

Objective: To analyze the relationship between a prethrombotic state and the occurrence of thrombosis, as well as survival time for patients with cervical cancer. Methods: Patients with first diagnosis of cervical cancer were subgrouped according to FIGO staging, and two D-dimer levels were assessed. According to the results, patients are divided into an observation group (abnormal) and control group (normal). Results: For 106 patients with cervical cancer, 38 with abnormal D-dimer, the abnormal rate is 35.9%, of which stage I accounted for 6.5%, stage II 38.5%, stage III 50%, and stage IV 61.1% (p=0.013); The level of D-dimers in stageI wass $0.87{\pm}0.68ug/ml$, while in stage II it was $1.50{\pm}1.35ug/ml$, stage III $2.60{\pm}1.86ug/ml$ and stage IV $18.6{\pm}53.4ug/ml$ (P=0.031); after follow-up of patients for 2-30 months, the mortality of observation group is 21.1%, while for control group it was 2.94% (p <0.01). In the observation group, survival time was $15.1{\pm}5.8$ months, while for control group it was $21.0{\pm}5.4$ months, the difference between two groups being highly significant (p=0.000). Conclusion: There is a direct correlation between prethrombotic state and the grade malignancy of cervical cancer. The level is positively correlated with clinical stage, and is inversely related to survival time, so that a prethrombotic state could be used to predict the prognosis for patients with cervical cancer.

Prostate cancer is common all around the world. Hormonal therapy is the mainstay of therapy, however castration-resistant prostate cancer (CRPC) becomes a serious problem and needs further clinical trials with novel agents. Novel agents like cabazitaxel, abireterone acetate or enzalutamide are encouraging but we do not know which one is the best in metastatic CRPC. In here, treatment modalities for metastatic CRPC are discussed witha mini-review of the literature.

A direct connection between certain lifestyle factors and an increased risk of cancer has already been established. Despite well-documented associations, controversial messages on causes of cancer often appear without taking into consideration their impact on the general population. While mainstream coverage of cancer research is clearly welcome, consideration must be given to the risk of transmitting provocative messages with serious negative consequences for cancer research and public health. We must avoid becoming a breeding ground for the misinterpretation of scientific information. Polemical results can stimulate scientific research and progress, but controversial messages encourage confusion and impotence in an increasingly disoriented population. The correct communication of health messages is at least as important as research on risk factors.