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Mongolia

Cancer Statistics
Population in 2008: 2.6m
People newly diagnosed with cancer (excluding NMSC) / yr: 4,300
Age-standardised rate, incidence per 100,000 people/yr: 242.2
Risk of getting cancer before age 75:25.0%
People dying from cancer /yr: 3,100
Data from IARC GlobalCan (2008)
Mongolia Cancer Organisations and Resources
Latest Research Publications Related to Mongolia

Mongolia Cancer Organisations and Resources (2 links)


Latest Research Publications Related to Mongolia

Oyunchimeg B, Hwang JH, Ahmed M, et al.
Complementary and alternative medicine use among patients with cancer in Mongolia: a National hospital survey.
BMC Complement Altern Med. 2017; 17(1):58 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Complementary and alternative medicine (CAM) use is popular in former Soviet Central Asian countries including Mongolia. However, no studies are available on CAM use among patients with cancer in countries of this region. The aim of this research is to describe the prevalence and patterns of CAM use by patients with cancer in Mongolia.
METHODS: A cross-sectional study was conducted using data from 482 cancer patients attending the National Cancer Center in Mongolia from September 2015 to February 2016. The survey instrument included 25 questions regarding CAM used, factors associated with use of CAM, cancer-related characteristics, and participants' socio-demographic profile.
RESULTS: Among 482 respondents (response rate, 95.6%), 47.9% reported using one or more CAM modalities. Products of animal origin were the most popular modalities of CAM, followed by herbal products. Half of the users used CAM while receiving conventional treatment of cancer. Among users, only 29% discussed the CAM use with their doctors. Female gender, younger age, higher education, shorter disease duration, and prior use of CAM were significantly associated with CAM use.
CONCLUSIONS: CAM appears to be widely accepted by patients with cancer in Mongolia. The findings support the urgent need for further in-depth study into commonly used oral CAM products and their potential effects on health of patients with cancer in Mongolia. High prevalence of CAM use among cancer patients in our study warrants further studies in other countries of Central Asia.

Li DZ, Zhang QZ, Wang CY, et al.
Synthesis and antitumor activity of novel substituted uracil-1'(N)-acetic acid ester derivatives of 20(S)-camptothecins.
Eur J Med Chem. 2017; 125:1235-1246 [PubMed] Related Publications
A series of novel substituted uracil-1'(N)-acetic acid esters (6-20) of camptothecins (CPTs) were synthesized by the acylation method. These new compounds were evaluated for in vitro antitumor activity against tumor cell lines, A549, Bel7402, BGC-823, HCT-8 and A2780. In vitro results showed that most of the derivatives exhibited comparable or superior cytotoxicity compare to CPT (1) and topotecan (TPT, 2), with 12 and 13 possessing the best efficacy. Four compounds, 9, 12, 13 and 16, were selected to be evaluated for in vivo antitumor activity against H22, BGC-823 and Bel-7402 in mice. In vivo testing results indicated that 12 and 13 had antitumor activity against mouse liver carcinoma H22 close to Paclitaxel and cyclophosphamide. 12 had similar antitumor activity against human gastric carcinoma BGC-823 in nude mice compared to irinotecan (3) and possessed better antitumor activity against human hepatocarcinoma Bel-7402 in nude mice than 2. It is also discovered that 12 showed a similar mechanism but better inhibitory activity on topoisomerase I (Topo I) compared to 2. These findings indicate that 20(S)-O-fluorouracil-1'(N)-acetic acid ester derivative of CPTs, 12, could be developed as an antitumor drug candidate for clinical trial.

Xia Y, Zhang XL, Jin F, et al.
Apoptotic effect of sodium acetate on a human gastric adenocarcinoma epithelial cell line.
Genet Mol Res. 2016; 15(4) [PubMed] Related Publications
The objective of this study was to investigate the effect of sodium acetate on the viability of the human gastric adenocarcinoma (AGS) epithelial cell line. AGS cells were exposed to a range of concentrations of sodium acetate for different periods of time, and the sodium acetate-induced cytotoxic effects, including cell viability, DNA fragmentation, apoptotic gene expression, and caspase activity, were assessed. The changes in these phenotypes were quantified by performing a lactate dehydrogenase cell viability assay, annexin V staining, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL), and several caspase activity assays. In vitro studies demonstrated that the cytotoxicity of sodium acetate on the AGS cell line were dose- and time-dependent manners. No differences were found between the negative control and sodium acetate-treated cells stained with annexin V and subjected to the TUNEL assay. However, caspase-3 activity was increased in AGS cells exposed to sodium acetate. Overall, it was concluded that sodium acetate exerted an apoptotic effect in AGS cells via a caspase-dependent apoptotic pathway.

Huang C, Yu Z, Yang H, Lin Y
Increased MALAT1 expression predicts poor prognosis in esophageal cancer patients.
Biomed Pharmacother. 2016; 83:8-13 [PubMed] Related Publications
AIM: This study was designed to determine the expression of metastasis associated lung adenocarcinoma transcript 1 (MALAT1) in patients with esophageal cancer (EC). In addition, we attempted to seek the prognostic value of MALAT1 in EC based on its expression.
METHODS: The expression of MALAT1 in EC tissues and cell lines were measured by quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR). The association between MALAT1 expression and the clinical characteristics was analyzed using Chi-square test. Kaplan-Meier survival curves were plotted to describe the overall survival of EC patients with different expression of MALAT1. Cox regression analysis was per formed to evaluate the prognostic value of MALAT1 for EC patients.
RESULTS: Expression levels of MALAT1 were significantly higher in EC tissues and cells than the controls (P<0.05). MALAT1 expression was tightly related to lymphatic invasion (P=0.018), distant metastasis (P=0.033) and tumor differentiation (P=0.025), but shared no association with age, gender and tumor location (P>0.05). In addition, patients with high MALAT1 expression had a shorter overall survival than those with low MALAT1 (P<0.001). The results of Cox analysis shown that MALAT1 was significantly linked with the prognosis of EC patients (HR=6.638; P=0.000; 95% CI=2.948-14.947).
CONCLUSION: Taken together, the expression of MALAT1 could be a predictor for prognosis of EC patients.

Jiang N, Peng YP, Wang XY, et al.
Assessing the association between EFEMP1 rs3791679 polymorphism and risk of glioma in a Chinese Han population.
Genet Mol Res. 2016; 15(3) [PubMed] Related Publications
In this study, we assessed the association between the EFEMP1 rs3791679 polymorphism and glioma risk in a Chinese Han population. A total of 94 glioma patients and 206 healthy controls who conformed to the inclusion and exclusion criteria were recruited from Baogang Hospital between March 2012 and October 2014. The EFEMP1 rs3791679 gene polymorphism was assessed using a polymerase chain reaction-restriction fragment length polymorphism assay and the results were statistically analyzed using SPSS Statistics 17.0. The results of unconditional logistic regression analysis revealed that the GG genotype of EFEMP1 rs3791679 was positively correlated with increased susceptibility to glioma (adjusted OR = 2.09, 95%CI = 1.21-7.81). Moreover, the GG genotype of EFEMP1 rs3791679 was correlated with higher risk of glioma compared to the AA+GA genotype (OR = 2.60, 95%CI = 1.08-6.28) in the regressive model. In conclusion, we report that the EFEMP1 rs3791679 polymorphism influences glioma susceptibility in the Chinese Han population.

Wu Y, Dong L, Bao S, et al.
FK228 augmented temozolomide sensitivity in human glioma cells by blocking PI3K/AKT/mTOR signal pathways.
Biomed Pharmacother. 2016; 84:462-469 [PubMed] Related Publications
Temozolomide is a novel cytotoxic agent currently used as first-line chemotherapy for glioblastoma multiforme (GBM). Romidepsin (FK228), a histone deacetylase inhibitor, is a promising new class of antineoplastic agent with the capacity to induce growth arrest and/or apoptosis of cancer cells. However, combination of the two drugs in glioma remains largely unknown. In the present study, we evaluated the combinatory effects of FK228 with TMZ in glioma, and its molecular mechanisms responsible for these effects. Glioma cell lines were treated with TMZ, FK228 or the combination of drugs. The resistance effect including cytotoxicity and apoptosis was determined in glioma cells, respectively. We further evaluated the effects of FK228 in the PI3K/Akt-signaling pathway in vitro. Mice engrafted with 5×10(6) LN382 cells were treated with TMZ, FK228 or the combination of two drugs, and tumor weights and volumes were measured, respectively. FK228 enhanced the cytotoxic effects of TMZ in glioma cells compared to vehicle-treated controls or each drug alone. The combination of FK228 and TMZ-induced apoptosis was demonstrated by increased expression of cleaved-Caspase 3, Bax, cleaved-PARP, and decreased Bcl-2 expression. Furthermore, the expression of key components of the PI3K/Akt-signaling pathway showed that combination of FK228 and TMZ block PI3K/Akt pathways in vitro. This block effect was also confirmed in vivo in mice models. Mice treated with both FK228 and TMZ drugs showed significantly reduced tumor weights and volumes, compared to each drug alone. Our results suggested that FK228 augmented temozolomide sensitivity in human glioma cells partially by blocking PI3K/AKT/mTOR signal pathways. It thus may provide a promising target for improving the therapeutic outcome of TMZ-resistant gliomas, although further studies will be needed.

Li J, Bao B, Liu L, Wang X
Near-Infrared Fluorescence Imaging of Carbonic Anhydrase IX in Athymic Mice Bearing HT-29 Tumor Xenografts.
Biomed Res Int. 2016; 2016:6825712 [PubMed] Free Access to Full Article Related Publications
Near-infrared fluorescence (NIRF) imaging technology is a highly sensitive imaging modality and has been widely used in noninvasively studying the status of receptor expression in small animal models, with an appropriate NIRF probe targeting a specific receptor. In this report, Cy5.5-conjugated anti-CAIX monoclonal antibody (Mab-Cy5.5) was evaluated in athymic mice bearing HT-29 tumor xenografts in order to investigate the effect of conjugate on tumor targeting efficacy. In vitro binding studies showed that Mab-Cy5.5 could specifically bind to the cells which expressed CAIX. Results from in vivo imaging showed that HT-29 tumor xenografts can be clearly visualized at 48 h after injection of Mab-Cy5.5, and in the blocking experiment, free anti-CAIX antibody effectively blocked the concentration of Mab-Cy5.5 in the tumors. Western blotting and immunohistochemistry analysis of HT-29 tumor xenografts verified the expression of CAIX in HT-29 tumors. Mab-Cy5.5 could specifically bind to the tumors which expressed CAIX. These results suggested that Mab-Cy5.5 was suitable for CAIX expression imaging in the preclinical research.

RaFiei E, Mohammadian-Hafshejani A, Towhidi F, et al.
Lack of Any Relationship of Stomach Cancer Incidence and Mortality with Development in Asia.
Asian Pac J Cancer Prev. 2016; 17(8):3777-83 [PubMed] Related Publications
BACKGROUND: The aim of this study was to evaluate the incidence and mortality of stomach cancer, and its relationship with the Human Development Index (HDI) and its components in Asia in 2012.
MATERIALS AND METHODS: This ecological study was conducted based on GLOBOCAN project of WHO for Asian countries. We assessed the correlations between standardized incidence rates (SIR) and standardized mortality rates (SMR) of stomach cancer with HDI and its components using SPSS18.
RESULTS: A total of 696,231 cases (68.7% in males and 31.3% in females, ratio of 2.19:1) and 524,465 deaths (67.1% in men and 33.0% in women, ratio 2.03:1) were included in 2012. Five countries with the highest SIR of stomach cancer were Republic Korea, Mongolia, Japan, China and Tajikistan. Five countries with the highest SMR of stomach cancer were Mongolia, Tajikistan, Kyrgyzstan, Kazakhstan and China. Correlation between HDI and SIR was 0.241 (p = 0.106), in men 0.236 (p = 0.114) and in women -0.250 (p = 0.094). Also between HDI and SMR -0.250 (p = 0.871) in men -0.018 (p = 0.903) and in women -0.014 (p = 0.927).
CONCLUSIONS: No significant correlation was observed between the SIR of stomach cancer, and the HDI and its dimensions, such as life expectancy at birth, mean years of schooling, and income level of the population.

Wang J, Zhao X, Shi J, et al.
miR-451 suppresses bladder cancer cell migration and invasion via directly targeting c-Myc.
Oncol Rep. 2016; 36(4):2049-58 [PubMed] Related Publications
MicroRNA (miRNA) expression is shown dysregulated in tumors. It has been reported that miR-451 alters gene expression and regulates tumorigenesis in various cancer tissues. However, its underlying biological significance in bladder cancer remains to be clarified. In the present study, we investigated the function and molecular mechanism of miR-451 involved in bladder cancer cell migration and invasion. Our results showed that miR-451 was downregulated in clinical bladder carcinoma tissues compared with adjacent bladder tissues. Overexpression of miR-451 significantly retarded the proliferation, migration and invasion of bladder cancer T24 and 5637 cells in vitro. Moreover, the attenuated cell migration and invasion by miR-451 was correlated with increased apoptosis. However, our dual-luciferase reporter assay validated that c-Myc, an oncogene in many tumors, was a direct target gene of miR-451 in bladder cancer. The expression of c-Myc was repressed by miR-451 in bladder cancer cells, and knockdown of c-Myc mimicked the effects of miR-451 overexpression. This discovery suggested that miR-451 is a tumor suppressor modulating bladder cancer cell migration and invasion by directly targeting c-Myc. In addition, apoptosis promoted by miR-451 may participates in this biological behavior. Therefore, target miR-451 may be a novel therapeutic intervention for bladder cancer.

Tong L, Pan H, He J, et al.
Hepatoid adenocarcinoma arising from heterotopic pancreas of the ileum: A case report.
Medicine (Baltimore). 2016; 95(33):e4067 [PubMed] Related Publications
INTRODUCTION: Hepatoid adenocarcinoma (HAC) is a rare neoplasm with a striking morphologic similarity to hepatocellular carcinoma. The most common sites of HAC are the stomach, lung, and pancreas.
CASE REPORT: Here we report a rare case of HAC arising from the heterotopic pancreas (Heinrich type II) in the ileum with lymph node metastasis. A 56-year-old man was admitted to our hospital presenting with bloody stools under no obvious predisposing causes. The colonoscopy and the gastroscopy showed no pathological findings. A computed tomography scan showed an intussusception of ileum. Then partial resection of ileum was performed with end-to-end anastomosis and appendectomy. Histopathological examination showed a malignant transformation of heterotopic pancreas (Heinrich type II) in the ileum. We made the diagnosis of HAC based on clinical pathological features and immunochemical staining. The patient received chemotherapy and died 9 months later.
CONCLUSION: To our best knowledge, this is the first reported case of HAC originated from a heterotopic pancreas in the ileum. The clinical pathological features and immunochemical staining are important for correct diagnosis of HAC.

Zheng N, Bai X, Niu R, Wang X
Primary Pulmonary Mucinous Adenocarcinoma Was Better Visualized on Delayed FDG PET/CT Imaging.
Clin Nucl Med. 2016; 41(10):809-11 [PubMed] Related Publications
A 36-year-old man underwent FDG PET/CT to evaluate a lung mass in the right middle lobe. The mass on the early PET images that were acquired 50 minutes post-FDG injection had only minimally increased FDG activity with uptake ratio between the mass and mediastinal blood pool of 0.93. However, on the delayed images acquired 230 minutes post-FDG administration, this ratio increased to 3.0, which enabled better notion of the lesion. Pathological examination demonstrated a primary pulmonary mucinous adenocarcinoma.

Wen LM, Wu WZ, Peng XC
Identifying significant pathways of hepatitis B virus-related hepatocellular carcinoma based on crosstalk and network pathways.
Genet Mol Res. 2016; 15(2) [PubMed] Related Publications
This study aims to identify significant pathways in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) based on the pathway network strategy. We proposed a pathway network where a protein-protein interaction (PPI) network was integrated with the crosstalk of pathways. Pathway data were first obtained from background PPI network, Reactome pathway database, and common genes between mRNA differentially expressed genes (DEGs), and miRNA target genes of HBV-related HCC. Pathway interactions were subsequently randomly extracted based on gene-gene interactions, and a weight value was assigned to each crosstalk using the Spearman correlation coefficient. Finally, pathways and crosstalk were visualized via Cytoscape to construct the final pathway network. A total of 9 common genes were identified between 396 mRNA DEGs and 400 miRNA target genes, and 17 pathways were identified based on background pathways and common genes. In addition, we constructed a pathway network that included 136 interactions and 17 pathways. The weight value of netrin-1 signaling and regulation of Frizzled proteins (FZD) by ubiquitination was the largest, at 0.228. In conclusion, we identified 17 significant pathways that might act as potential biomarkers of HBV-related HCC. This information may offer some insight into treatment and detection of HBV-related HCC.

Lkhagvadorj S, Kim JH, Oh SS, et al.
Orai1 Expression Is Closely Related with Favorable Prognostic Factors in Clear Cell Renal Cell Carcinoma.
J Korean Med Sci. 2016; 31(6):879-85 [PubMed] Free Access to Full Article Related Publications
Store-operated calcium (Ca(2+)) entry (SOCE) is the principal Ca(2+) entry route in non-excitable cells, including cancer cells. We previously demonstrated that Orai1 and STIM1, the molecular components of SOCE, are involved in tumorigenesis of clear cell renal cell carcinoma (CCRCC). However, a clinical relevance of Orai1 and STIM1 expression in CCRCC has been ill-defined. Here, we investigated the expression of Orai1 and STIM1 in CCRCC, and compared their expression with clinico-pathological parameters of CCRCC and the patients' outcome. Immunohistochemical staining for Orai1 and STIM1 was performed on 126 formalin fixed paraffin embedded tissue of CCRCC and western blot analysis for Orai1 was performed on the available fresh tissue. The results were compared with generally well-established clinicopathologic prognostic factors in CCRCC and patient survival. Membrane protein Orai1 is expressed in the nuclei in CCRCC, whereas STIM1 shows the cytosolic expression pattern in immunohistochemical staining. Orai1 expression level is inversely correlated with CCRCC tumor grade, whereas STIM1 expression level is not associated with tumor grade. The higher Orai1 expression is significantly associated with lower Fuhrman nuclear grade, pathologic T stage, and TNM stage and with favorable prognosis. The expression level of STIM1 is not correlated with CCRCC grade and clinical outcomes. Orai1 expression in CCRCC is associated with tumor progression and with favorable prognostic factors. These results suggest that Orai1 is an attractive prognostic marker and therapeutic target for CCRCC.

Mohammadian M, Soroush A, Mohammadian-Hafshejani A, et al.
Incidence and Mortality of Liver Cancer and Their Relationship with Development in Asia.
Asian Pac J Cancer Prev. 2016; 17(4):2041-7 [PubMed] Related Publications
BACKGROUND: Liver cancer (LC) is the sixth world most common cancer and the second leading cause of cancer death. Due to the importance and necessity of awareness about the incidence and mortality of diseases to perform prevention programs, this study focused on data for LC and its relationship with the human development index (HDI) and its components in Asia in 2012.
MATERIALS AND METHODS: This ecological study was based on GLOBOCAN data for Asian countries. We assessed correlations between standardized incidence rates (SIR) and standardized mortality rates (SMR) of LC with HDI and its components using of SPSS18.
RESULTS: A total of 582,420 incident cases and 557,097 deaths were recorded in Asian countries in 2012. The five with the highest SIR were Mongolia, Lao PDR, Vietnam, Republic of Korea and Thailand and those with the highest SMR were Mongolia, Lao PDR, Vietnam, Cambodia and Thailand. A negative relation was observed between HDI and LC for SIR of 0.049 (P=0.748) and for SMR of 0.07 (P=0.645), with life expectancy at birth a positive relation for SIR of 0.061 (P=0.687) and a negative relation for SMR of 0.079 (P=0.603), with the average years of education a negative relation fo SIR of 0.476 (p=0.952) and for SMR of 0.032 (P=0.832), and with the country income level per person a negative relation for SMI of 0.11 (p=0.465) and for SMR of 0.113 (P=0.455).
CONCLUSIONS: The incidence of LC is more in less developed and developing countries but statistically significant correlations were not found between standardized incidence and mortality rates of LC, and HDI and its dimensions.

Zhang YF, Yu Y, Song WZ, et al.
miR-410-3p suppresses breast cancer progression by targeting Snail.
Oncol Rep. 2016; 36(1):480-6 [PubMed] Related Publications
miR-410-3p acts as an oncogene or tumor-suppressor gene in various types of cancer. However, its role in breast cancer remains unknown. In the present study, expression of miR-410-3p in 30 breast cancer and paired adjacent normal tissues was detected by RT-qPCR. The expression of miR-410-3p was downregulated in 76.7% of the breast cancer samples. To further validate the expression of miR-410-3p in breast cancer, we analyzed miR-410-3p expression profiling data set from The Cancer Genome Atlas (TCGA) including 683 breast cancer and 87 normal breast tissues. We observed that the expression of miR-410-3p was downregulated in breast cancer tissues. Next, we investigated the influence of miR-410-3p on cell proliferation by transiently transfecting the miR-410-3p mimic or inhibitor, as well as their corresponding controls in the MDA-MB-231 and MCF7 cell lines. miR-410-3p overexpression reduced cell growth, colony formation and the number of EdU-positive cells in the MDA-MB-231 cells. In contrast, inhibition of miR-410-3p in the MCF7 cells resulted in a higher proliferation rate as assessed by MTT assay, plate colony formation and EdU assays. Furthermore, miR-410-3p inhibited epithelial-mesenchymal transition. In addition, Snail was found to be a direct target of miR-410-3p based on a luciferase assay. Overexpression of Snail was able to rescue the effect of miR-410-3p in breast cancer cells. Moreover, miR‑410-3p was inversely expressed with Snail in breast cancer samples. Our data provide new knowledge regarding the role of miR-410-3p in breast cancer progression.

Li S, Hong H, Lv H, et al.
SIRT 1 Overexpression is Associated with Metastasis of Pancreatic Ductal Adenocarcinoma (PDAC) and Promotes Migration and Growth of PDAC Cells.
Med Sci Monit. 2016; 22:1593-600 [PubMed] Free Access to Full Article Related Publications
BACKGROUND SIRT 1, as a class III histone deacetylase (HDAC), is implicated in the initiation and progression of malignancies. However, the association of SIRT 1 with tumorigenesis or progression of pancreatic ductal adenocarcinoma (PDAC) is not clear. MATERIAL AND METHODS In our study we investigated SIRT 1 expression in PDAC samples and evaluated the association of SIRT 1 level with the clinical and pathological characteristics of PDAC patients. We investigated the role of SIRT 1 in the migration and growth of PDAC PANC-1 or BxPC-3 cells using gain-of-function and loss-of-function approach. RESULTS We demonstrated that SIRT 1 mRNA level was significantly promoted in intra-tumor tissues compared to peri-tumor tissues of PDAC; and SIRT 1 overexpression was markedly associated with distant or lymph node (LN) metastasis of these PDAC tissues. Moreover, the in vitro wound healing assay demonstrated that SIRT 1 overexpression with lentivirus vector markedly promoted the migration of PANC-1 or BxPC-3 cells, whereas SIRT 1 knockdown using SIRT 1 specific siRNA transfection significantly inhibited the migration of PDAC cells. The colony forming assay confirmed SIRT 1 promotion of the growth of PANC-1 or BxPC-3 cells. CONCLUSIONS In summary, SIRT 1 overexpression is significantly associated with metastasis of PDAC, and overexpressed SIRT 1 plays an important role in pancreatic cancer cell migration and growth. Our data warrants further studies on SIRT 1 as a novel chemotherapeutic target in PDAC.

Li K, Li X, Wu Z, et al.
Adenovirus encoding XAF-1 and TNF‑α in the same open reading frame efficiently inhibits hepatocellular cancer cells.
Mol Med Rep. 2016; 13(6):5169-76 [PubMed] Related Publications
X‑linked inhibitor of apoptosis (XIAP)‑associated factor 1 (XAF‑1), a tumor suppressor, is downregulated in most human malignant tumors. However, the tumor suppressive role of XAF‑1 in hepatocellular carcinoma (HCC) and its therapeutic value require further elucidation. The present study examined the expression of XAF‑1 at the mRNA and protein level in the HCC and paired peritumor tissue specimens, as well as in HCC cell lines and a normal liver cell line. A recombinant adenovirus which co‑expressed XAF‑1 and TNF‑α was then constructed, and its effects on the proliferation and colony formation ability of the MHCC97H HCC cell line were assessed using apoptosis induction, flow cytometry, trypan blue staining assay and a clonogenic assay. The results demonstrated that the expression of XAF‑1 was significantly reduced in HCC tissues compared with that in their matched peritumor specimens, and a significant correlation with the tumor size, stage and tumor ‑ nodes ‑ metastasis stage was identified. The reduced levels of XAF‑1 were further confirmed the HCC cell lines MHCC97L, HepG2 and MHCC97H compared with those in the L02 normal liver cell line. The recombinant adenovirus Ad‑XAF‑1&TNF‑α, which co‑expressed XAF‑1 and TNF‑α, was shown to efficiently express the two proteins at the mRNA and protein level. Furthermore, infection with Ad‑XAF‑1&TNF‑α synergistically induced apoptosis, reduced the proliferation and colony formation ability of MHCC97L cells to a significantly greater extent than overexpression of XAF‑1 or TNF‑α individually. To the best of our knowledge, the present study was the first to construct an adenovirus which co‑expressed XAF‑1 and TNF‑α in the same open reading frame and expressed them proportionally. As Ad‑XAF‑1&TNF‑α inhibited HCC cells with enhanced efficiency, it may be applicable for the treatment of HCC.

Li RH, Zhang AM, Li S, et al.
Multiple differential expression networks identify key genes in rectal cancer.
Cancer Biomark. 2016; 16(3):435-44 [PubMed] Related Publications
BACKGROUND: Rectal cancer is an important contributor to cancer mortality.
OBJECTIVE: The objective of this paper is to identify key genes across three phenotypes (fungating, polypoid and polypoid & small-ulcer) of rectal cancer based on multiple differential expression networks (DENs).
METHODS: Differential interactions and non-differential interactions were evaluated according to Spearman correlation coefficient (SCC) algorithm, and were selected to construct DENs. Topological analysis was performed for exploring hub genes in largest components of DENs. Key genes were denoted as intersections between nodes of DENs and rectal cancer associated genes from Genecards. Finally, we utilized hub genes to classify phenotypes of rectal cancer on the basis of support vector machines (SVM) methodology.
RESULTS: We obtained 19 hub genes and total 12 common key genes of three largest components of DENs, and EGFR was the common element. The SVM results revealed that hub genes could classify phenotypes, and validated feasibility of DEN methods.
CONCLUSIONS: We have successfully identified significant genes (such as EGFR and UBC) across fungating, polypoid and polypoid & small-ulcer phenotype of rectal cancer. They might be potential biomarkers for classification, detection and therapy of this cancer.

Chen L, Wang W, Cao L, et al.
Long Non-Coding RNA CCAT1 Acts as a Competing Endogenous RNA to Regulate Cell Growth and Differentiation in Acute Myeloid Leukemia.
Mol Cells. 2016; 39(4):330-6 [PubMed] Free Access to Full Article Related Publications
Long non-coding RNAs (lncRNAs) are involved in multiple cellular events, as well as in tumorigenesis. Colon cancer-associated transcript-1 (CCAT1) gene encodes an lncRNA whose over-activation was observed in an expanding list of primary human solid tumors and tumor cell lines, however its biological roles in acute myeloid leukaemia (AML) has not been reported yet at present. In this study, the aberrant upregulation of CCAT1 was detected in French-American-British M4 and M5 subtypes of adult AML patients. By gain- and loss-of-function analysis, we determined that CCAT1 repressed monocytic differentiation and promoted cell growth of HL-60 by sequestering tumor suppressive miR-155. Accordingly, a significant decrease in miR-155 level was detected in AML patients. Re-introduction of miR-155 into HL-60 cells restored monocytic maturation and repressed cell proliferation. Furthermore, CCAT1 could up-regulated c-Myc via its competing endogenous RNA (ceRNA) activity on miR-155. In conclusion, these results revealed new mechanism of lncRNA CCAT1 in AML development, and suggested that the manipulation of CCAT1 expression could serve as a potential strategy in AML therapy.

Hu HQ, Wang F, Du X, et al.
Genetic variability of XRCC1 influences the treatment outcome of gastric cancer.
Genet Mol Res. 2016; 15(1) [PubMed] Related Publications
We aimed to investigate the role of XRCC1 codon 194 (Arg>Trp), 280 (Arg>His), and 399 (Arg>Gln) polymorphisms in response to chemotherapy and the overall survival of gastric cancer patients. A total of 172 patients were recruited for our study between January 2010 and March 2012. Genotyping of the three XRCC1 codons was carried out by restriction fragment length polymorphism polymerase chain reaction. By logistic regression analysis, we found that the Trp/Trp genotype of XRCC1 194 (Arg>Trp) showed a stronger association with complete or partial response to chemotherapy compared to the Arg/Arg genotype, and the adjusted odds ratio (95%CI) was 0.17 (0.05-0.58). Moreover, the Trp/Trp genotype was associated with a higher risk of death than that with the Arg/Arg genotype based on multivariate Cox proportional hazard regression analysis, and the adjusted hazard ratio (95%CI) was 4.08 (1.20-14.19). In conclusion, we found that the XRCC1 194 (Arg>Trp) polymorphism was correlated with a better response to chemotherapy and a low risk of death in patients with gastric cancer.

Zhang H, Guo G, Jianzhong C, Zheng Y
Decreased Level of IgE is Associated with Breast Cancer and Allergic Diseases.
Med Sci Monit. 2016; 22:587-97 [PubMed] Free Access to Full Article Related Publications
BACKGROUND The aim of this study was to explore the prevalence of type I allergic diseases in patients with breast cancer by carrying out a questionnaire survey and IgE detection in a healthy population and in patients with breast cancer. MATERIAL AND METHODS There were 309 patients enrolled and they were further divided into the type I allergic disease group, the newly diagnosed breast cancer with type I allergic disease group, the re-visit breast cancer with type I allergic disease group, and the re-visit breast cancer without type I allergic disease group, as well as a healthy control group. Serum total IgE level was detected by immunoassay. RESULTS The IgE value in the healthy population with type I allergic diseases (89.3±51.4 IU/ml) was significantly higher than in those without type I allergic diseases (45.6±65.1 IU/ml). There was no significant difference between IgE values in the re-visit breast cancer patients with type I allergic disease (25.1±65.1 IU/ml) and those without type I allergic disease (23.0±45.9 IU/ml). The area under the ROC curve was 0.618±0.04, sensitivity was 78%, specificity was 47.1%, Youden index was 0.251, and IgE threshold was 32.6 IU/ml. CONCLUSIONS The patients with newly diagnosed breast cancer were susceptible to type I allergic disease at about the same levels as in the healthy population. There was no correlation between breast cancer and type I allergic disease.

Wang D, An G, Xie S, et al.
The clinical and prognostic significance of CD14(+)HLA-DR(-/low) myeloid-derived suppressor cells in hepatocellular carcinoma patients receiving radiotherapy.
Tumour Biol. 2016; 37(8):10427-33 [PubMed] Related Publications
Myeloid-derived suppressor cells (MDSCs) are key player in mediating systemic immunosuppression, and their accumulation and expansion in the periphery and tumor have been iteratively observed in patients with various types of cancer. It has been reported that CD14(+)HLA-DR(-/low) MDSCs are increased in hepatocellular carcinoma (HCC) patients; however, the clinical significance of MDSC alteration in HCC patients after treatment is poorly studied. In this study, we examined the frequency of MDSCs in 92 HCC patients, 14 chronic liver disease patients without HCC, and 22 healthy controls by flow cytometric analysis. The associations between the clinical features and the frequency of MDSCs were analyzed. In particular, we further examined the prognostic impact of MDSCs on the overall survival of HCC patients receiving radiation therapy. The frequency of MDSCs in HCC patients was significantly increased and correlated with tumor stage, size, burden, and Child-Pugh classification but not with biochemical parameters of liver function. In HCC patients who received radiation therapy, the frequency of MDSCs after treatment significantly decreased and was inversely correlated with overall survival time. In multivariate analysis, only post-treatment MDSC ratio and Child-Pugh classification were correlated with the prognosis of HCC patients. Patients with a high frequency of MDSCs after radiotherapy should be closely followed, and the inhibition of MDSCs may improve the prognosis of patients.

Ji K, Zhang L, Zhang M, et al.
Prognostic Value and Clinicopathological Significance of p-stat3 Among Gastric Carcinoma Patients: A Systematic Review and Meta-Analysis.
Medicine (Baltimore). 2016; 95(5):e2641 [PubMed] Free Access to Full Article Related Publications
The overexpression of phosphorylated signal transducer and activator of transcription 3 (p-stat3) was detected in a variety of human tumors. The published studies on p-stat3 expression among gastric carcinoma patients remain controversial.In order to clarify the prognosis value of p-stat3 with overall survival and its association with clinicopathological characteristics in gastric carcinoma, we performed a systematic review and meta-analysis.Eligible studies were retrieved by searching PubMed, Embase, Cochrane library, and Chinese biomedical literature service system databases.Studies described the association between p-stat3 expression and clinicopathological characteristics and overall survival in gastric carcinoma patients; p-stat3 expression was detected by immunohistochemistry (IHC).Odds ratio (OR) and hazard ratio (HR) were considered as a measure of evaluating the association in meta-analysis; I was used to assess the heterogeneity across studies; publication bias was assessed with funnel plot, Egger test, and Begg test.Twenty-three studies including 2872 patients which evaluated the p-stat3 expression by IHC in gastric carcinoma were included. The pooled HR (HR = 2.02, 95% CI: 1.49-2.73, P < 0.00001) indicated that the increased p-stat3 expression was significantly associated with poor overall survival. In addition, when we investigated the association between p-stat3 overexpression and clinicopathological characteristics of gastric carcinoma, we found that the increased p-stat3 expression was significantly associated with tumor differentiation (poorly vs well-moderately: OR = 3.70, 95% CI: 1.98-6.93, P < 0.0001) and lymph node metastasis (present vs absent: OR = 2.40, 95% CI: 1.28-4.50, P = 0.007).The different type of primary antibody was used; the assessment methods of p-stat3 positive expression were defined differently; the locations of p-stat3 expression were different; the method of extrapolating HR from Kaplan-Meier survival curves did seem to be less reliable than when HR was extracted directly from literatures; sample sizes, the age of patients, and the follow-up durations are different.In conclusion, our meta-analysis indicates that the increased p-stat3 expression may be not only predict poor prognosis, but also be associated with worse tumor differentiation and lymph node metastasis in patients with gastric carcinoma.

Bai RX, Wang WP, Zhao PW, Li CB
Ghrelin attenuates the growth of HO-8910 ovarian cancer cells through the ERK pathway.
Braz J Med Biol Res. 2016; 49(3) [PubMed] Free Access to Full Article Related Publications
Ovarian cancer is one of the most common causes of death from gynecologic tumors and is an important public health issue. Ghrelin is a recently discovered bioactive peptide that acts as a natural endogenous ligand of the growth hormone secretagogue receptor (GHSR). Several studies have identified the protective effects of ghrelin on the mammalian reproductive system. However, little research has been done on the effects of ghrelin on ovarian cancer cells, and the underlying mechanisms of these effects. We sought to understand the potential involvement of mitogen-activated protein kinases (MAPKs) in ghrelin-mediated inhibition of growth of the ovarian line HO-8910. We applied different concentrations of ghrelin and an inhibitor of the ghrelin receptor (D-Lys3-GHRP-6) to HO-8910 cells and observed the growth rate of cells and changes in phosphorylation of the MAPKs ERK1/2, JNK and p38. We discovered that ghrelin-induced apoptosis of HO-8910 cells was though phosphorylated ERK1/2, and that this phosphorylation (as well as p90rsk phosphorylation) was mediated by the GHSR. The ERK1/2 pathway is known to play an essential part in the ghrelin-mediated apoptosis of HO-8910 cells. Hence, our study suggests that ghrelin inhibits the growth of HO-8910 cells primarily through the GHSR/ERK pathway.

Zhao R, Chen G
Role of GSTP1 Ile105Val and XRCC1 Arg194Trp, Arg280His and Arg399Gln gene polymorphisms in the clinical outcome of advanced non-small cell lung cancer.
Int J Clin Exp Pathol. 2015; 8(11):14909-16 [PubMed] Free Access to Full Article Related Publications
We conducted a study to investigate the association between the clinical outcome and GSTP1 Ile105Val and XRCC1 Arg194Trp, Arg280His and Arg399Gln gene polymorphisms in advanced NSCLC patients with cisplatin-based chemotherapy. Between January 2010 and December 2012, a total of 206 patients with advanced NSCLC were histopathologically confirmed were included into analysis. By logistic regression analysis, individuals carrying the AG and GG genotypes of GSTP1 Ile105Val were associated with better response to chemotherapy when compared with the AA genotype, and the adjusted Ors (95% CI) were 2.06 (1.10-3.86) and 4.89 (1.52-18.33), respectively. The TT genotype of XRCC1 Arg194Trp was correlated with better response to chemotherapy compared to the CC genotype, and the adjusted OR (95% CI) was 3.23 (1.20-9.30). By Cox Hazard Proportional Model, the GG genotype of GSTP1 Ile105Val and the TT genotype of XRCC1 Arg194Trp were found to be associated with lower risk of death from all causes when compared with the wide-type genotype, and the adjusted HRs (95% CI) were 0.05 (0.01-0.18) and 0.20 (0.07-0.62), respectively. Moreover, individuals carrying both the G/A+G/G genotype of GSTP1 Ile105Val and the G/A+A/A of XRCC1 Arg194Trp were associated with heavy greater CR+PR response to chemotherapy (OR=2.98, 95% CI=1.39-6.42), and also correlated with longer overall survival of advanced NSCLC (HR=0.19, 95% CI=0.05-0.61). In conclusion, we found that the GSTP1 Ile105Val and XRCC1 Arg194Trp were associated with better response to chemotherapy and longer survival of advanced NSCLC, compared to the wide-type genotype.

Mo R, Peng J, Xiao J, et al.
High TXNDC5 expression predicts poor prognosis in renal cell carcinoma.
Tumour Biol. 2016; 37(7):9797-806 [PubMed] Related Publications
Clear cell renal cell carcinoma (ccRCC) is the most common primary kidney cancer in adults, and the identification of biomarkers involved in the pathogenesis and prognosis of ccRCC is crucial for early diagnosis and anticancer treatment. In this study, we demonstrate that thioredoxin domain-containing protein 5 (TXNDC5) expression is markedly upregulated in ccRCC tissues in comparison with adjacent non-cancerous tissues through quantitative RT-PCR, Western blotting, and immunohistochemical analyses. Importantly, TXNDC5 expression is negatively correlated with the overall survival of patients. Knockdown of TXNDC5 by siRNAs inhibits the cell growth, migration, and invasion of ccRCC cells as well as sensitizes ccRCC cells to chemotherapeutic drugs, such as Camptothecin and 5-Fluorouracil. Moreover, we used complementary DNA (cDNA) microarray analyses to explore the underlying molecular mechanisms of TXNDC5 in the pathogenesis of ccRCC. We demonstrate that knockdown of TXNDC5 affects the messenger RNA (mRNA) and protein levels of numerous important genes associated with tumorigenesis. In summary, our findings indicate that TXNDC5 performs an essential function in ccRCC pathogenesis and can serve as a novel prognostic marker of ccRCC.

Yu Y, Lv F, Lin H, et al.
Mitochondrial ND3 G10398A mutation: a biomarker for breast cancer.
Genet Mol Res. 2015; 14(4):17426-31 [PubMed] Related Publications
Mitochondrial DNA mutations have been found to play important roles in carcinogenesis. The most common G10398A mutation, a non-conservative amino acid substitution from Thr to Ala, seems to be involved in the tumorigenesis of breast cancer. Results from studies concerning this mutation remain inconclusive. In the current study, we first took clinical and molecular datasets from case-control studies to determine the association between the G10398A mutation and breast cancer. We further used the Phylotree to determine the haplogroups of this mutation. The frequencies of this mutation in 500 unrelated healthy controls were also screened. We found that this mutation is very common in the human population, and may be a polymorph.

Dong W, Cui J, Yang J, et al.
Decreased expression of Rab27A and Rab27B correlates with metastasis and poor prognosis in colorectal cancer.
Discov Med. 2015; 20(112):357-67 [PubMed] Related Publications
The Rab27 subfamily of secretory small GTPase plays a vital role in vesicle trafficking and regulates tumor growth and metastasis in several cancer types. Thus, this research was designed to explore the clinical and prognostic significance of Rab27A and Rab27B in colorectal cancer (CRC) patients. Reverse transcription-polymerase chain reaction (RT-PCR), western blot, and immunohistochemistry (IHC) analysis were used to examine Rab27A and Rab27B expression in human CRC cell lines and primary tumors. The correlation of gene expression with clinicopathological features and prognosis was also evaluated. Our results indicated that Rab27A expression was down-regulated in primary tumors compared with matched adjacent tissues (100%, 8/8), as detected by western blot. IHC analysis revealed that the positive expression rate of Rab27A in primary CRC tissues was lower than in adjacent normal tissues (P = 0.005). Negative expression of Rab27A and Rab27B significantly correlated with poor tumor differentiation (both P < 0.001) and positive vascular invasion (P = 0.005, P = 0.021, respectively). Moreover, absence of Rab27A was associated with advanced tumor node metastasis (TNM) stage (P = 0.006), distant metastasis (P = 0.002), and local recurrence (P = 0.038). Survival analysis also showed a significant correlation between unfavorable survival and negative expression of Rab27A (P = 0.002). In addition, positive expression of both Rab27A and Rab27B was a protective factor in CRC. In conclusion, decreased expression of Rab27A and Rab27B, especially Rab27A, closely correlated with tumor progression and are valuable prognostic indicators in CRC patients.

Lv X, Yang F, Guo X, et al.
Hypersplenism is correlated with increased risk of hepatocellular carcinoma in patients with post-hepatitis cirrhosis.
Tumour Biol. 2016; 37(7):8889-900 [PubMed] Related Publications
Several risk factors exist for hepatocellular carcinoma in patients with post-hepatitis cirrhosis (PHC), including hypersplenism. Splenectomy is a common but controversial procedure in the management of hypersplenism, but its impact on hepatocellular carcinoma (HCC) remains uncertain. We conducted a hospital-based study of PHC patients to identify potential risk factors, including a history of splenectomy, which has been associated with progression from PHC to HCC. From 2002 to 2012, 2678 patients developed hypersplenism secondary to PHC. Of these patients, 828 developed HCC and 1850 did not. Potential risk factors of HCC were determined by univariate and multivariate analyses to exclude confounding variables. Odds ratios (ORs) and 95 % confidence intervals (95 % CIs) were determined for each factor. Many factors, such as liver function, platelet (PLT) counts, Child-Pugh class, and history of hepatitis, were associated with progression to HCC. PHC patients with hypersplenism who displayed elevated levels of alanine transaminase (ALT), aspartate transaminase (AST), γ-glutamyltransferase (GGT), ALK, phosphatase, and prolonged prothrombin time (PT) had a significantly increased risk of HCC. However, the patients who had splenectomy showed better liver function test results and less progression to HCC. In patients with PHC and hypersplenism, abnormal levels of ALT, AST, ALP, and GGT and prolonged PT are risk factors of HCC. Splenectomy, as the intervention method of hypersplenism, is performed less frequently in patients who developed HCC than in patients who did not develop HCC. Therefore, splenectomy may act as an independent factor that is significantly associated with HCC development.

Wei PL, Huang CY, Tai CJ, et al.
Glucose-regulated protein 94 mediates metastasis by CCT8 and the JNK pathway in hepatocellular carcinoma.
Tumour Biol. 2016; 37(6):8219-27 [PubMed] Related Publications
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer death worldwide. Cancer metastasis is a major obstacle in clinical cancer therapy. The mechanisms underlying the metastasis of HCC remain unclear. Glucose-regulated protein 94 (GRP94) is a key protein involved in mediating cancer progression, and it is highly expressed in HCC specimens. However, the role of GRP94 in cancer metastasis is unclear. A specific short hairpin RNA (shRNA) was employed to knock down GRP94 gene expression in HCC cell lines. Wound-healing migration, transwell migration, and invasion assays were performed to determine the migration and invasive ability of HCC cells. We demonstrated that silencing GRP94 inhibited HCC cell wound healing, migration, and invasion. Furthermore, our findings indicated that GRP94 knockdown might attenuate HCC cell metastasis by inhibiting CCT8/c-Jun/EMT signaling. Our study indicated that silencing GRP94 significantly reduced the migration and invasion abilities of HCC cells. Moreover, depleting GRP94 inhibited cell migration and invasion by downregulating CCT8/c-Jun signaling. Thus, our data suggest that the GRP94/CCT8/c-Jun/EMT signaling cascade might be a new therapeutic target for HCC.

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