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Molecular Carcinogenesis

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https://www.readbyqxmd.com/read/28485511/combination-of-nexrutine-and-docetaxel-suppresses-nf%C3%AE%C2%BAb-mediated-activation-of-c-flip
#1
Yangang Zhang, Li Li, Jingyu Wang, Wei Cheng, Jiandong Zhang, Xueting Li, Zhenhua Zhang, Jingjing Gong, Rita Ghosh, Addanki Pratap Kumar, Jianping Xie
Lack of effective options following failure to conventional chemotherapeutic agent such as Docetaxel is a major clinical challenge in the management of prostate cancer. These observations underscore the need for deciphering the underlying mechanism of docetaxel resistance to enable the development of effective therapeutic approaches. We observed up regulation of the anti-apoptotic protein c-FLIP and its up stream regulators including receptor tyrosine kinase RON and transcription factor NFκB (p65) in tumors obtained from metastatic prostate cancer patients...
May 9, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28485478/long-noncoding-rna-has2-as1-mediates-hypoxia-induced-invasiveness-of-oral-squamous-cell-carcinoma
#2
Guiquan Zhu, Shaoxin Wang, Jin Chen, Zhaohui Wang, Xinhua Liang, Xiaoyi Wang, Jian Jiang, Jinyi Lang, Ling Li
A hypoxic microenvironment plays important roles in the progression of solid tumors, including oral squamous cell carcinoma (OSCC). Long noncoding RNAs (lncRNAs) have gained much attention in the past few years. However, it is not clear whether lncRNAs can regulate hypoxia adaptation of OSCC or which lncRNAs participate in this process. Using a lncRNA microarray, we analyzed the aberrant lncRNA expression profiles in OSCC tissues compared with paired normal oral mucosa and in hypoxic OSCC cells compared with normoxic OSCC cells...
May 9, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28470829/soluble-mica-is-elevated-in-pancreatic-cancer-results-from-a-population-based-case-control-study
#3
Guillaume Onyeaghala, Heather H Nelson, Bharat Thyagarajan, Amy M Linabery, Angela Panoskaltsis-Mortari, Myron Gross, Kristin E Anderson, Anna E Prizment
OBJECTIVES: Pancreatic cancer is diagnosed at a late stage and has one of the highest cancer mortality rates in the U.S., creating an urgent need for novel early detection tools. A candidate biomarker for use in early detection is the soluble MHC class I-related chain A (s-MICA) ligand, which pancreatic tumors shed to escape immune detection. The objective of this study was to define the association between s-MICA levels and pancreatic cancer, in a population-based case-control study...
May 4, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28470764/glyoxalase-2-drives-tumorigenesis-in-human-prostate-cells-in-a-mechanism-involving-androgen-receptor-and-p53-p21-axis
#4
Cinzia Antognelli, Ivana Ferri, Guido Bellezza, Paola Siccu, Harold D Love, Vincenzo Nicola Talesa, Angelo Sidoni
Glyoxalase 2 (Glo2), a metabolic enzyme, is overexpressed in some human cancers which suggests this enzyme may play a role in human tumorigenesis. In prostate cancer (PCa) the role of Glo2 has been scarcely investigated and there are no studies addressing a causative involvement of this protein in this neoplasia. Here we examined the immunohistochemical profile of Glo2 in human PCa and benign adjacent tissues and investigated Glo2 involvement in PCa development in human prostate cell lines. PCa and matched adjacent normal tissues were obtained from paraffin sections of primary PCa from 20 patients who had undergone radical prostatectomy...
May 4, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28467689/vernodalol-enhances-trail-induced-apoptosis-in-diffuse-large-b-cell-lymphoma-cells
#5
Wenjun Wu, Yang Yang, Gang Deng, Liang Ma, Guoqing Wei, Gaofeng Zheng, Xiaoyan Han, Donghua He, Yi Zhao, Jinsong He, Zhen Cai, Rui Yu
Tumour necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a potent anti-tumour agent that triggers apoptosis in cells from multiple types of carcinoma but not in normal cells. However, diverse mechanisms are associated with insensitivity to TRAIL in various cancers. TRAIL efficacy may be enhanced by combining TRAIL with a sensitizer. In this study, vernodalol, a sesquiterpene lactone, sensitized diffuse large B-cell lymphoma (DLBCL) cells to TRAIL-induced apoptosis. Vernodalol increased the expression of death receptor (DR) 5, and silencing of DR5 with a small interfering RNA (siRNA) reduced the effect of vernodalol on TRAIL-mediated apoptosis...
May 3, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28467661/circulating-insulin-like-growth-factor-related-biomarkers-correlates-and-responses-to-calcium-supplementation-in-colorectal-adenoma-patients
#6
Caroline Y Um, Veronika Fedirko, W Dana Flanders, Christine Höflich, Elisa Wirthgen, Roberd M Bostick
Circulating insulin-like growth factor 1 (IGF-1) may be directly associated with colorectal cancer risk, and IGF binding protein 3 (IGFBP-3) is one of the most abundantly expressed binding proteins in various cancers. Calcium intakes, primarily from food, have been directly associated with circulating IGF-1, but whether supplemental calcium affects IGF-1 and IGFBP-3 is unknown. We tested the effects of 1.0 and 2.0 grams of supplemental elemental calcium daily on circulating IGF-1 and IGFBP-3 concentrations in colorectal adenoma patients in a randomized, double-blinded, placebo-controlled clinical trial (n=193)...
May 3, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28467612/high-mobility-group-a1-enhances-tumorigenicity-of-human-cholangiocarcinoma-and-confers-resistance-to-therapy
#7
Cristina Quintavalle, Katharina Burmeister, Salvatore Piscuoglio, Luca Quagliata, Eva Karamitopoulou, Romina Sepe, Alfredo Fusco, Luigi M Terracciano, Jesper B Andersen, Pierlorenzo Pallante, Matthias S Matter
High mobility group A1 (HMGA1) protein has been described to play an important role in numerous types of human carcinoma. By the modulation of several target genes HMGA1 promotes proliferation and epithelial-mesenchymal transition of tumor cells. However, its role in cholangiocarcinoma (CCA) has not been addressed yet. Therefore, we determined HMGA1 mRNA expression in CCA samples in a transcriptome array (n=104) and a smaller cohort (n=13) by qRT-PCR. Protein expression was evaluated by immunohistochemistry in a tissue microarray (n=67)...
May 3, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28467610/apurinic-apyrimidinic-endonuclease-1-ape1-ref-1-overexpression-is-an-independent-prognostic-marker-in-prostate-cancer-without-tmprss2-erg-fusion
#8
Manuela Juhnke, Asmus Heumann, Viktoria Chirico, Doris Höflmayer, Anne Menz, Andrea Hinsch, Claudia Hube-Magg, Martina Kluth, Dagmar S Lang, Christina Möller-Koop, Guido Sauter, Ronald Simon, Burkhard Beyer, Raisa Pompe, Imke Thederan, Thorsten Schlomm, Andreas M Luebke
Polymorphisms of the base excision repair gene APE1 may be associated with an increased risk for developing prostate cancer. In other cancer types, altered APE1 protein expression is a candidate prognostic marker. Using immunohistochemistry, we thus analyzed APE1 expression in 9,763 prostate cancers in a tissue microarray (TMA) with attached clinical and molecular data. The comparison with normal prostate tissue revealed an upregulation of APE1 in cancer samples. APE1 immunostaining was considered weak in 20...
May 3, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28418179/copy-number-variation-increased-gene-expression-and-molecular-mechanisms-of-neurofascin-in-lung-cancer
#9
Johanna Samulin Erdem, Yke Jildouw Arnoldussen, Vidar Skaug, Aage Haugen, Shanbeh Zienolddiny
Metastasis and cell adhesion are key aspects of cancer progression. Neurofascin (NFASC) is a member of the immunoglobulin superfamily of adhesion molecules and, while studies on NFASC are inadequate, other members have been indicated pivotal roles in cancer progression and metastasis. This study aimed at increasing the knowledge on the involvement of adhesion molecules in lung cancer progression by studying the regulation and role of NFASC in non-small cell lung cancer (NSCLC). Here, copy number variations in the NFASC gene were analyzed in tumor and non-tumorous lung tissues of 204 NSCLC patients...
April 18, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28418095/the-nuclear-orphan-receptor-nr4a1-regulates-%C3%AE-1-integrin-expression-in-pancreatic-and-colon-cancer-cells-and-can-be-targeted-by-nr4a1-antagonists
#10
Erik Hedrick, Syng-Ook Lee, Stephen Safe
β1-Integrin is highly expressed and is a negative prognostic factor for colon and pancreatic cancer patients and the gene plays a functional role in cell migration and invasion. In this study, we demonstrate that β1-integrin expression is regulated in pancreatic and colon cancer cells by the pro-oncogenic orphan nuclear receptor 4A1 (NR4A1, Nur77, TR3) and knockdown of this receptor by RNA interference decreases β1-integrin protein and mRNA expression, α5-integrin, and also expression of β1-integrin-dependent phosphorylation of FAK (pFak)...
April 18, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28418088/rack1-forms-a-complex-with-fgfr1-and-pkm2-and-stimulates-the-growth-and-migration-of-squamous-lung-cancer-cells
#11
Chengzhi Zhou, Tao Chen, Zhanhong Xie, Yinyin Qin, Yangming Ou, Jiexia Zhang, Shiyue Li, Rongchang Chen, Nanshan Zhong
Phosphorylation of Pyruvate Kinase M2 (PKM2) on Tyr105 by fibroblast growth factor receptor 1 (FGFR1) has been shown to promote its nuclear localization as well as cell growth in lung cancer. Better understanding the regulation of this process would benefit the clinical treatment for lung cancer. Here, it has been found that the adaptor protein receptor for activated PKC kinase (RACK1) formed a complex with FGFR1 and PKM2, and activated the FGFR1/PKM2 signaling. Knocking down the expression of RACK1 impaired the phosphorylation on Tyr105 of PKM2 and inhibited the growth and migration of lung cancer cells, while over-expression of RACK1 in lung cancer cells led to the resistance to Erdafitinib...
April 18, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28418082/non-digestible-carbohydrates-supplementation-increases-mir-32-expression-in-the-healthy-human-colorectal-epithelium-a-randomized-controlled-trial
#12
Fiona C Malcomson, Naomi D Willis, Iain McCallum, Long Xie, Bart Lagerwaard, Seamus Kelly, D Michael Bradburn, Nigel J Belshaw, Ian T Johnson, John C Mathers
Colorectal cancer (CRC) risk is modulated by diet and there is convincing evidence of reduced risk with higher non-digestible carbohydrates (NDCs) consumption. Resistant starch (RS), a NDC, positively modulates the expression of oncogenic microRNAs, suggesting that this could be a mechanism through which NDCs protect against CRC. The present study aimed to investigate the effects of supplementation with two NDCs, RS, and polydextrose (PD), on microRNA expression in the macroscopically-normal human rectal epithelium using samples from the DISC Study, a randomized, double-blind, placebo-controlled dietary intervention...
April 18, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28418078/induction-of-mitochondrial-apoptotic-pathway-in-triple-negative-breast-carcinoma-cells-by-methylglyoxal-via-generation-of-reactive-oxygen-species
#13
Anirban Roy, Manisha Ahir, Saurav Bhattacharya, Pravat Kumar Parida, Arghya Adhikary, Kuladip Jana, Manju Ray
Triple negative breast cancer (TNBC) tends to form aggressive tumors associated with high mortality and morbidity which urge the need for development of new therapeutic strategies. Recently the normal metabolite Methylglyoxal (MG) has been documented for its anti-proliferative activity against human breast cancer. However, the mode of action of MG against triple negative breast cancer remains open to question. In our study, we investigated the anticancer activity of MG in MDA MB 231 and 4T1 TNBC cell lines and elucidated the underlying mechanisms...
April 18, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28398634/ski-regulates-smads-and-taz-signaling-to-suppress-lung-cancer-progression
#14
Mian Xie, Xiaojun Wu, Jinjun Zhang, Jiexia Zhang, Xiangxiang Li
Ski, the transforming protein of the avian Sloan-Kettering retrovirus, displays both pro-oncogenic and anti-oncogenic activities in human cancer. The mechanisms underlying these conflicting observations have not been fully understood. Herein, we investigated the mechanism underlying the tumor suppressor activity of Ski. To investigate the effect of Ski re-activation on TGF-β and Hippo/TAZ pathway, we measured its effect on the endogenous Smad target genes (PAI-1 and P15(INK4B) ) and TAZ target gene CTGF. The results revealed that Ski exerted its inhibitory activity in TGF-β1/Smad signaling pathway...
April 11, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28398627/aryl-hydrocarbon-receptor-promotes-hepatocellular-carcinoma-tumorigenesis-by-targeting-intestine-specific-homeobox-expression
#15
Shih-Hsien Hsu, Li-Ting Wang, Chee-Yin Chai, Chi-Cheng Wu, Edward Hsi, Shyh-Shin Chiou, Shen-Nien Wang
The aryl hydrocarbon receptor (AHR), a major chemical sensor, is thought to play a role in various biological contexts, including cell cycle regulation and tumorigenesis. However, its regulatory mechanisms remain unclear. We propose herein a novel mechanism through which AHR promotes tumorigenesis by targeting expression of the oncogene intestine-specific homeobox (ISX) in hepatocellular carcinoma (HCC). Compared to paired tumor-adjacent tissues and non-HCC tumors, HCCs exhibited an increased and hierarchical pattern of AHR expression...
April 11, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28398609/potentially-functional-variants-in-lncrnas-are-associated-with-breast-cancer-risk-in-a-chinese-population
#16
Yue Jiang, Fangzhi Du, Fei Chen, Na Qin, Zhu Jiang, Jin Zhou, Tao Jiang, Zhening Pu, Yue Cheng, Jiaping Chen, Juncheng Dai, Hongxia Ma, Guangfu Jin, Zhibin Hu, Hao Yu, Hongbing Shen
Long non-coding RNAs (lncRNAs) participate in the development of breast cancer. Genetic variants in lncRNAs may be involved in their abnormal expressions and associated with cancer risk. In the present study, we performed RNA sequencing on five paired breast cancer tumor and adjacent non-cancerous tissues to obtain differentially expressed lncRNAs. We systematically selected potential regulatory variants of these lncRNAs and investigated the associations between these variants and breast cancer susceptibility in 1486 breast cancer cases and 1519 cancer-free controls in a Chinese population...
April 11, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28398603/kctd20-promotes-the-development-of-non-small-cell-lung-cancer-through-activating-fak-akt-pathway-and-predicts-poor-overall-survival-of-patients
#17
Xiupeng Zhang, Haijing Zhou, Lin Cai, Chuifeng Fan, Yang Liu, Liang Wang, Qingchang Li, Yuan Miao
Kctd20 (potassium channel tetramerization protein domain containing 20) is a positive regulator of Akt signaling. However, the role of Kctd20 during the course of tumorigenesis and development is unclear. Using immunohistochemistry, we demonstrated that, in non-small cell lung cancer (NSCLC) patients, Kctd20 protein expression significantly correlates with advanced TNM stage (P < 0.001), positive status for regional lymph node metastasis (P = 0.019), and poor overall survival (P = 0.013). Proliferation and invasion assays showed that Kctd20 dramatically promotes the proliferation and invasion of NSCLC cells (P = 0...
April 11, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28383782/the-mir-200b-zeb1-circuit-regulates-diverse-stemness-of-human-hepatocellular-carcinoma
#18
Shu-Chun Tsai, Chen-Chun Lin, Tsung-Chieh Shih, Rong-Jeng Tseng, Ming-Chin Yu, Yu-Jr Lin, Sen-Yung Hsieh
Accumulating evidence suggests that human hepatocellular carcinoma (HCC) can be derived from cancer stem cells (CSCs), which contribute to tumor initiation, metastasis, chemoresistance, and recurrence. A great variety of HCC CSCs resulting in diverse clinical manifestations have been reported. However, how CSC diversity is regulated and generated remains unclear. Here we report that the miR-200b-ZEB1 circuit is closely involved with the induction and maintenance of a diverse group of CSCs. We found that miR-200b downregulation occurred in early HCC and associated with poor prognosis...
April 6, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28383763/upregulated-mir-132-in-lgr5-gastric-cancer-stem-cell-like-cells-contributes-to-cisplatin-resistance-via-sirt1-creb-abcg2-signaling-pathway
#19
Lanfang Zhang, Xiaohe Guo, Dezhong Zhang, Yingying Fan, Lei Qin, Shuping Dong, Lanfang Zhang
Cisplatin resistance has long been a major problem that restricts its use. A novel paradigm in tumor biology suggests that gastric tumor chemo-resistance is driven by gastric cancer stem cell-like (GCSCs). Growing evidence has indicated that microRNAs (miRNAs) contributes to chemo-resistance in gastric cancer (GC). Here, Lgr5(+) cells derived from gastric cancer cell lines displayed stem cell-like features. Flow cytometry demonstrated the presence of a variable fraction of Lgr5 in 19 out of 20 GC specimens...
April 6, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28370334/mir-27a-regulates-the-tgf-%C3%AE-signaling-pathway-by-targeting-smad2-and-smad4-in-lung-cancer
#20
Dong-Kyu Chae, Eunmi Ban, Young Sook Yoo, Eunice EunKyeong Kim, Ja-Hyun Baik, Eun Joo Song
The transforming growth factor-β (TGF-β) signaling pathway is associated with carcinogenesis and various biological processes. SMAD2 and SMAD4, which are putative tumor suppressors, have an important role in TGF-β signaling. The aberrant expression of these genes is implicated in some cancers. However, the mechanisms of SMAD2 and SMAD4 dysregulation are poorly understood. In this study, we observed that miR-27a was upregulated in lung cancer cell lines and patients. In addition, SMAD2 and SMAD4 genes were identified as targets of miR-27a by several target prediction databases and experimental validation...
March 31, 2017: Molecular Carcinogenesis
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