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Juri Bergmann, Miryam Müller, Niklas Baumann, Manuel Reichert, Carola Heneweer, Julia Bolik, Karsten Lücke, Sabine Gruber, Antonella Carambia, Susanne Boretius, Ivo Leuschner, Thomas Becker, Björn Rabe, Johannes Herkel, F Thomas Wunderlich, Hans-Willi Mitrücker, Stefan Rose-John, Dirk Schmidt-Arras
: Hepatocellular carcinoma (HCC) is one of the most frequent tumors worldwide with rising incidence. The inflammatory cytokine interleukin 6 (IL-6) is a critical mediator of HCC development. It can signal through two distinct pathways, the IL-6 classic and the IL-6 trans-signaling pathway. While IL-6 classic signaling is important for innate and acquired immunity, IL-6 trans-signaling has been linked to accelerated liver regeneration and several chronic inflammatory pathologies. However, its implication in liver tumorigenesis has not been addressed yet...
October 22, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Anusha Sathyanarayanan, Karthik Subramanian Chandrasekaran, Devarajan Karunagaran
microRNAs (miRNAs) play significant roles in diverse biological processes and their deregulation is implicated in carcinogenesis. miR-146a executes tumour suppressive or oncogenic functions depending on the cancer type, but its effect on human cervical (CaCx) and colorectal (CRC) cancers have not been examined thus far. In this study, miR-146a exhibited high expression in CaCx but poor expression in CRC, in comparison to corresponding normal tissues. Nevertheless, ectopic expression of miR-146a inhibited proliferation in both CaCx and CRC cells and curbed their migration and invasion...
October 18, 2016: Biochemical and Biophysical Research Communications
Jolanda van Hengel, Celine Van den Broeke, Tim Pieters, Louis Libbrecht, Ilse Hofmann, Frans van Roy
p120 catenin (p120ctn) is required for the stability of classic cadherins at the cell surface and is thought to play a central role in modulating cell-cell adhesion. Cytoplasmic p120ctn promotes cell motility, and probably other activities, by modulating the activities of RhoA, Rac and Cdc42. E-cadherin is expressed in periportal but not in perivenous hepatocytes. In contrast, all hepatocytes of normal mouse liver express N-cadherin. Cholangiocytes express exclusively E-cadherin. Mice with p120ctn ablation in hepatocytes and cholangiocytes (p120LiKO mice) were generated by Cre-loxP technology...
October 15, 2016: European Journal of Cell Biology
Rosy, Rajendra N Goyal
A voltammetric sensor for the determination of 8-Hydroxydeoxyguanosine (8-OHdG); an important, sensitive and integral biomarker of oxidative stress and related pathological conditions like carcinogenesis, renal disorders, mental retardations, diabetes etc. has been fabricated. The synergistic behavior of two allotropic forms of carbon, which are electrochemically reduced graphene oxide (ErGO) and multiwalled carbon nanotubes (MWCNTs), has been exploited for the surface modification. The resulting modified surface has been characterized using Field Emission Scanning Electron Microscopy, X-ray diffraction, Electrochemical Impedance Spectroscopy and voltammetric behavior...
December 1, 2016: Talanta
Miao Liu, Ling Zhou, Baiyu Zhang, Minhong He, Xiaoying Dong, Xiaojun Lin, Chunhong Jia, Xiaochun Bai, Yifan Dai, Yongchun Su, Zhipeng Zou, Hang Zheng
Although epidemiological and preclinical studies have shown the preventative effect of n-3 polyunsaturated fatty acids (PUFAs) on colorectal cancer (CRC), the underlying molecular mechanisms are not clear. In this study, we revealed that elevation of n-3/n-6 PUFAs ratio suppress the mechanistic target of rapamycin complex 1 (mTORC1) and prevent colorectal tumorigenesis. The transgenic expression of fat-1, a desaturase that catalyzes the conversion of n-6 to n-3 PUFAs and produces n-3 PUFAs endogenously, repressed colorectal tumor cell growth and remarkably reduced tumor burden, and alleviated anemia as well as hyperlipidemia in APCMin/+ (adenomatous polyposis coli) mice, a classic CRC model that best simulates most clinical cases...
October 19, 2016: Oncotarget
Charles A Pickens, Mariana de Fátima Albuquerque Pereira, Jenifer I Fenton
Dietary lipid intake can be associated with an increased risk for colorectal cancer depending on its composition. Carcinogenesis alters lipid metabolism to facilitate cell growth and survival. For instance, metabolites of polyunsaturated fatty acids (PUFAs) are associated with increasing colon cell proliferation. Moreover, precancerous colon lesions (i.e. adenomas) increase the risk for colorectal cancer. In this study, we investigated associations between plasma PUFAs and the number of colon polyps and polyp type (i...
October 20, 2016: European Journal of Cancer Prevention
Ashton A Connor, Robert E Denroche, Gun Ho Jang, Lee Timms, Sangeetha N Kalimuthu, Iris Selander, Treasa McPherson, Gavin W Wilson, Michelle A Chan-Seng-Yue, Ivan Borozan, Vincent Ferretti, Robert C Grant, Ilinca M Lungu, Eithne Costello, William Greenhalf, Daniel Palmer, Paula Ghaneh, John P Neoptolemos, Markus Buchler, Gloria Petersen, Sarah Thayer, Michael A Hollingsworth, Alana Sherker, Daniel Durocher, Neesha Dhani, David Hedley, Stefano Serra, Aaron Pollett, Michael H A Roehrl, Prashant Bavi, John M S Bartlett, Sean Cleary, Julie M Wilson, Ludmil B Alexandrov, Malcolm Moore, Bradly G Wouters, John D McPherson, Faiyaz Notta, Lincoln D Stein, Steven Gallinger
Importance: Outcomes for patients with pancreatic ductal adenocarcinoma (PDAC) remain poor. Advances in next-generation sequencing provide a route to therapeutic approaches, and integrating DNA and RNA analysis with clinicopathologic data may be a crucial step toward personalized treatment strategies for this disease. Objective: To classify PDAC according to distinct mutational processes, and explore their clinical significance. Design, Setting, and Participants: We performed a retrospective cohort study of resected PDAC, using cases collected between 2008 and 2015 as part of the International Cancer Genome Consortium...
October 20, 2016: JAMA Oncology
Meital Charni, Ronit Aloni-Grinstein, Alina Molchadsky, Varda Rotter
Regeneration and tumorigenesis share common molecular pathways, nevertheless the outcome of regeneration is life, whereas tumorigenesis leads to death. Although the process of regeneration is strictly controlled, malignant transformation is unrestrained. In this review, we discuss the involvement of TP53, the major tumor-suppressor gene, in the regeneration process. We point to the role of p53 as coordinator assuring that regeneration will not shift to carcinogenesis. The fluctuation in p53 activity during the regeneration process permits a tight control...
October 21, 2016: Cell Death and Differentiation
Sara S Franco, Karolina Szczesna, Maria S Iliou, Mohammed Al-Qahtani, Ali Mobasheri, Julianna Kobolák, András Dinnyés
Cancer cells, stem cells and cancer stem cells have for a long time played a significant role in the biomedical sciences. Though cancer therapy is more effective than it was a few years ago, the truth is that still none of the current non-surgical treatments can cure cancer effectively. The reason could be due to the subpopulation called "cancer stem cells" (CSCs), being defined as those cells within a tumour that have properties of stem cells: self-renewal and the ability for differentiation into multiple cell types that occur in tumours...
September 30, 2016: BMC Cancer
Terezinha M Souza, Linda Rieswijk, Twan van den Beucken, Jos Kleinjans, Danyel Jennen
Chemical carcinogenesis, albeit complex, often relies on modulation of transcription through activation or repression of key transcription factors. While analyzing extensive networks may hinder the biological interpretation, one may focus on dynamic network motifs, among which persistent feed-forward loops (FFLs) are known to chronically influence transcriptional programming. Here, to investigate the relevance a FFL-oriented approach in depth, we have focused on aflatoxin B1-induced transcriptomic alterations during distinct states of exposure (daily administration during 5 days followed by a non-exposed period) of human hepatocytes, by exploring known interactions in human transcription...
October 17, 2016: Toxicology
E Fehri, E Ennaifer, R Bel Haj Rhouma, L Guizani-Tabbane, I Guizani, S Boubaker
Toll-like receptor 9 (TLR9) plays a major role in the fight against DNA viruses infections. Despite its antitumor properties, inappropriate activation of TLR9 during chronic inflammation may cause the activation of transcription factors inducing pro-cancerous activities. Thus, the relationship between TLR9 and cancer remains highly confrontational especially in gynecological cancers and cervical cancer induced by viruses. In this review, we focus on the beneficial and detrimental role of TLR9 in gynecological carcinogenesis...
July 2016: Current Research in Translational Medicine
Jia Nan, Wang Jieyu, Li Qing, Tao Xiang, Chang Kaikai, Hua Keqin, Yu Yinhua, Wong Kwong-Kwok, Feng Weiwei
This work investigated the role of paired box 2 (PAX2) in endometrial cancer and its epigenetic regulation mechanism. Endometrial cancer tissues and cell lines exhibited increased PAX2 expression compared with hyperplasia, normal endometrium and endometrial epithelial cells. Knock-down of PAX2 resulted in reduced cell viability, invasion and migration, and PAX2 overexpression caused the opposite effects. Increased methylation of the PAX2 promoter was observed in both cancer tissues and cell lines and was positively correlated with PAX2 expression...
October 13, 2016: Oncotarget
Yuguang Zhao, Lei Yang, Di Wu, Hua He, Mengmeng Wang, Tingwen Ge, Yudi Liu, Huimin Tian, Jiuwei Cui, Lin Jia, Ziqiang Wan, Fujun Han
PURPOSE: We conducted two meta-analyses of ATM genetic polymorphisms and cancer risk in individuals with or without radiation exposure to determine whether there was a joint effect between the ATM gene and radiation exposure in carcinogenesis. RESULTS: rs1801516, which was the only ATM polymorphism investigated by more than 3 studies of radiation exposure, was eligible for the present study. The meta-analysis of 23333 individuals without radiation exposure from 24 studies showed no association between the rs1801516 polymorphism and cancer risk, without heterogeneity across studies...
October 18, 2016: Oncotarget
Yu-Chuan Huang, Chung-Ta Lee, Jenq-Chang Lee, Yao-Wen Liu, Ying-Jen Chen, Joseph T Tseng, Jui-Wen Kang, Bor-Shyang Sheu, Bo-Wen Lin, Liang-Yi Hung
MicorRNA-137 is silenced in human colorectal cancer tissues and colon polyps. Our study showed that the decreased expression of miR-137 is significantly different in various types of polyp which maintain different potentials to lead to CRC development. The expression of miR-137 gradually decreases during the process of colorectal carcinogenesis. Receiver operating characteristic curve (ROC) analysis indicates that the loss of miR-137 expression in colon polyps can serve as a biomarker to predict the predisposition of colorectal carcinogenesis...
October 18, 2016: Oncotarget
Jing Wang, Bing Wang, Ling-Qiang Chen, Jin Yang, Zhi-Qiang Gong, Xue-Ling Zhao, Chun-Qiang Zhang, Kai-Li Du
OBJECTIVE: Osteosarcoma is a common malignancy with high rate of metastasis. miR-10b has been reported to be expressed in many types of tumors abnormally and be associated with cancer carcinogenesis and progression. But the function of miR-10b in osteosarcoma is still unknown. So this study was aimed to investigate the role of miR-10b in osteosarcoma development. METHODS: miR-10b expression in osteosarcoma tissues and osteosarcoma cells were detected using real time PCR...
October 17, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Nilton Lavatori Correa, Lidia Vasconcellos de Sá, Rossana Corbo
: An increase in the incidence of second primary cancers (SPC) is the late effect of greatest concern that could occur in differentiated thyroid carcinoma (DTC) patients treated with radioactive iodine (RAI). The decision to treat a patient with RAI should therefore incorporate a careful risk-benefit analysis. The objective of this work is to adapt the risk estimation models developed by the Biological Effects of Ionizing Radiation Committee (BEIR VII) to local epidemiological characteristics, to assess the carcinogenesis risk from radiation in a population of Brazilian DTC patients treated with RAI...
October 20, 2016: Thyroid: Official Journal of the American Thyroid Association
Reza Dabiri, Touraj Mahmoudi, Hamid Farahani, Hossein Nobakht, Mohammad Reza Zali
BACKGROUND: With regard to the effect of calcium against colorectal cancer (CRC) and considering the key role of calcium sensing receptor (CaSR) in calcium homeostasis, this study investigated whether CaSR gene rs1801725 or A986S variant was associated with susceptibility to CRC risk. METHODS: This study was conducted as a case-control study and 303 cases with CRC and 354 controls were enrolled. All 657 subjects were genotyped for CaSR gene A986S variant using PCR-RFLP method...
August 2016: Iranian Journal of Cancer Prevention
Meng Wu, Lishann Ingram, Ezequiel J Tolosa, Renzo E Vera, Qianjin Li, Sungjin Kim, Yongjie Ma, Demetri D Spyropoulos, Zanna Beharry, Jiaoti Huang, Martin E Fernandez-Zapico, Houjian Cai
Although the differentiation of oncogenically transformed basal progenitor cells is one of the key steps in prostate tumorigenesis, the mechanisms mediating this cellular process are still largely unknown. Here we demonstrated that an expanded p63+ and CK5+ basal/progenitor cell population, induced by the concomitant activation of oncogenic Kras(G12D) and androgen receptor (AR) signaling, underwent cell differentiation in vivo. The differentiation process led to suppression of the p63 expressing cells with a decreased number of CK5+ basal cells, but an increase of CK8+ luminal tumorigenic cells, and revealed a hierarchal lineage pattern consisting of p63+/CK5+ progenitor, CK5+/CK8+ transitional progenitor, and CK8+ differentiated luminal cells...
October 19, 2016: Journal of Biological Chemistry
B Ślaska, L Grzybowska-Szatkowska, M Bugno-Poniewierska, A Gurgul, A Śmiech, D Różańska, J Dudka
The aim of the study was to identify polymorphisms and mutations in the mitochondrial ND4 gene and to analyse the associations between the occurrence of molecular changes in mtDNA and phenotypic traits in tumours in German Shepherd dogs. Fifty samples obtained from blood and tumour tissues of German Shepherd dogs with diagnosed tumours were analysed. DNA extraction, amplification, and sequencing of the mtDNA ND4 gene, and bioinformatics, statistical, and in silico protein coding SNP analyses were performed...
September 1, 2016: Polish Journal of Veterinary Sciences
Ying Liu, Chaoting Zhang, Weijiao Gao, Limin Wang, Yaqi Pan, Yunong Gao, Zheming Lu, Yang Ke
HPV integration plays an important role in cervical carcinogenesis. HPV genotypes and the exact integration sites were investigated using HPV capture technology combined with next generation sequencing in 166 women. Three, one and six integration sites were verified in 7 HPV-positive 'normal cervical epithelium', 6 HPV-positive CIN2 and 15 HPV-positive CIN 3 samples, respectively. Of the 10 integrations, one and nine were involved with HPV33 and HPV16, respectively. Our study accurately evaluated HPV integration level in CINs and normal cervical tissues using high-throughput viral integration detection method providing basic evidence for HPV integration-driven cervical carcinogenesis...
October 19, 2016: Scientific Reports
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