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Molecular Carcinogenesis

Sembulingam Tamilzhalagan, Dhanasekaran Rathinam, Kumaresan Ganesan
Frequent amplification of 7q21-22 genomic region is known in gastric cancer. Multiple genes including SHFM1, MCM7 and COL1A2 were reported to be the potential cancer candidate genes of this 20 Mb amplicon. This amplicon has two polycistrionic miRNA clusters and in the present study, miR-106b-25 cluster located in intron-13 of MCM7 was identified to express in gastric tumors. Among the 7q21-22 candidate genes, SHFM1 & MCM7 are expressed in intestinal type gastric tumors, whereas COL1A2 is expressed in diffuse type gastric tumors...
January 6, 2017: Molecular Carcinogenesis
Jessica Dittmann, Angelique Ziegfeld, Lars Jansen, Mieczyslaw Gajda, Vera Kloten, Edgar Dahl, Ingo B Runnebaum, Matthias Dürst, Claudia Backsch
Progression from human papillomavirus-induced premalignant cervical intraepithelial neoplasia (CIN) to cervical cancer (CC) is driven by genetic and epigenetic events. Our microarray-based expression study has previously shown that inter-α-trypsin-inhibitor heavy chain 5 (ITIH5) mRNA levels in CCs were significantly lower than in high-grade precursor lesions (CIN3s). Therefore, we aimed to analyze in depth ITIH5 expression during cervical carcinogenesis in biopsy material and cell culture. Moreover, functional analyses were performed by ectopic expression of ITIH5 in different cell lines...
January 6, 2017: Molecular Carcinogenesis
Wenjing Zhu, Yiqun Shao, Yu Peng
MicroRNAs have been reported to be associated with chemosensitivity of several types of cancers. However, the underlying molecular mechanisms are poorly understood. In this study, we explored miR-218 increased the chemosensitivity to cis-diaminedichloroplatinum treatment of prostate cancer. We found that the expression level of miR-218 was down-regulated in the human prostate cancer specimens. Moreover, overexpression of miR-218 inhibited cell viability, migration and invasion in PC3 and DU145 cells. Furthermore, we demonstrated that the tumor suppressive role of miR-218 was mediated by negatively regulating branched-chain amino acid transaminase 1 (BCAT1) protein expression...
January 4, 2017: Molecular Carcinogenesis
Mahamat Babagana, Sydney Johnson, Hannah Slabodkin, Wiam Bshara, Carl Morrison, Eugene S Kandel
BRAF is a commonly mutated oncogene in various human malignancies and a target of a new class of anti-cancer agents, BRAF-inhibitors (BRAFi). The initial enthusiasm for these agents, based on the early successes in the management of metastatic melanoma, is now challenged by the mounting evidence of intrinsic BRAFi-insensitivity in many BRAF-mutated tumors, by the scarcity of complete responses, and by the inevitable emergence of drug resistance in initially responsive cases. These setbacks put an emphasis on discovering the means to increase the efficacy of BRAFi and to prevent or overcome BRAFi-resistance...
January 4, 2017: Molecular Carcinogenesis
Rakesh Sathish Nair, Easwaran Potti Manoj, Ratheeshkumar Thankappan, Sivakumar Krishnankutty Chandrika, M R Prathapachandra Kurup, Priya Srinivas
Novel chelated metal complexes were synthesized from carbohydrazones and thiocarbohydrazones using metal-based drug designing platforms and their combination effect with Pb, a naphthaquinone were analyzed for anticancer activity in breast cancer cell lines. A panel of BRCA1 wild type and mutated breast cancer cells: MCF-7 (BRCA1(+) / ER(+) ), MDA-MB-231 (BRCA1(+) / ERα(-) ), HCC-1937 (BRCA1(-) / ERα(-) ), HCC1937/wt BRCA1, MX1 (BRCA1(-) / ERα(-) ) and MDA-MB-436 (BRCA1(-) / ERα(-) ) were screened for anti-cancer activity...
January 4, 2017: Molecular Carcinogenesis
Bryan Harder, Wang Tian, James J La Clair, Aik-Choon Tan, Aikseng Ooi, Eli Chapman, Donna D Zhang
The NRF2 pathway activates a cell survival response when cells are exposed to xenobiotics or are under oxidative stress. Therapeutic activation of NRF2 can also be used prior to insult as a means of disease prevention. However, prolonged expression of NRF2 has been shown to protect cancer cells by inducing the metabolism and efflux of chemotherapeutics, leading to both intrinsic and acquired chemoresistance to cancer drugs. This effect has been termed the "dark side" of NRF2. In an effort to combat this chemoresistance, our group discovered the first NRF2 inhibitor, the natural product brusatol, however the mechanism of inhibition was previously unknown...
December 26, 2016: Molecular Carcinogenesis
Pei-Li Yao, Liping Chen, Tomasz P Dobrzański, Bokai Zhu, Boo-Hyon Kang, Rolf Müller, Frank J Gonzalez, Jeffrey M Peters
Neuroblastoma is a common childhood cancer typically treated by inducing differentiation with retinoic acid (RA). Peroxisome proliferator-activated receptor-β/δ, (PPARβ/δ) is known to promote terminal differentiation of many cell types. In the present study, PPARβ/δ was over-expressed in three human neuroblastoma cell lines, NGP, SK-N-BE(2) and IMR-32, that exhibit high, medium and low sensitivity, respectively, to retinoic acid-induced differentiation to determine if PPARβ/δ and retinoic acid receptors (RARs) could be jointly targeted to increase the efficacy of treatment...
December 20, 2016: Molecular Carcinogenesis
Masafumi Yoshimoto, Aoi Tokuda, Kunihiko Nishiwaki, Kazuo Sengoku, Yuji Yaginuma
PICT-1 is a nucleolar protein with various tumor suppressor functions. Recently, PICT-1 expression was reported to be dramatically reduced in several cancers. To investigate the role of PICT-1 in uterine cervical carcinogenesis, we examined its gene mutations, protein expression, cellular localization, and effect on p53 stabilization. PCR-SSCP analysis of the entire coding region of PICT-1 showed that a polymorphism at codon 389 may increase the risk of uterine cervical cancers, and also identified a novel missense mutation...
December 20, 2016: Molecular Carcinogenesis
Xinfang Yu, Wei Li, Qipan Deng, Shuo You, Haidan Liu, Songling Peng, Xiaolan Liu, Jingchen Lu, Xiangjian Luo, Lifang Yang, Min Tang, Xinxian Weng, Wei Yi, Wenbin Liu, Shengqi Wu, Zhihui Ding, Tao Feng, Jian Zhou, Jia Fan, Ann M Bode, Zigang Dong, Jikai Liu, Ya Cao
Neoalbaconol, derived from Albatrellus confluens, shows anti-cancer activities in the previously study, but its role in angiogenesis is unknown. Here, we determined whether neoalbaconol could attenuate angiogenesis and how does it occur. Data demonstrated that neoalbaconol could inhibit the proliferation of breast cancer cells and induce apoptosis. Also, neoalbaconol suppressed vascular endothelial growth factor (VEGF)-induced human umbilical vascular endothelial cells (HUVECs) proliferation, migration, invasion, and capillary-like tube formation in vitro and reduced tumor angiogenesis in vivo...
December 20, 2016: Molecular Carcinogenesis
Zhaofan Luo, Yanan Li, Zuo Mingxin, Chang Liu, Dong Yan, Huamin Wang, Donghui Li
NR5A2 (aka LRH-1) has been identified as a pancreatic cancer susceptibility gene with missing biological link. This study aims to demonstrate expression and potential role of NR5A2 in pancreatic cancer. NR5A2 expression was quantified in resected pancreatic ductal adenocarcinomas and the normal adjacent tissues of 134 patients by immunohistochemistry. The intensity and extent of NR5A2 staining was quantified and analyzed in association with overall survival (OS). The impact of NR5A2 knockdown on pancreatic cancer stem cell (CSC) properties and epithelial-mesenchymal transition (EMT) markers was examined in cancer cells using RT-PCR and Western Blot...
December 20, 2016: Molecular Carcinogenesis
Xiaonian Zhu, Daochuan Li, Zhengbao Zhang, Wei Zhu, Wenxue Li, Jian Zhao, Xiumei Xing, Zhini He, Shan Wang, Fangping Wang, Lu Ma, Qing Bai, Xiaowen Zeng, Jie Li, Chen Gao, Yongmei Xiao, Qing Wang, Liping Chen, Wen Chen
Identification of aberrant histone H3 phosphorylation during chemical carcinogenesis will lead to a better understanding of the substantial roles of histone modifications in cancer development. To explore whether aberrant H3 phosphorylation contributes to chemical carcinogenesis, we examined the dynamic changes of H3 phosphorylation at various residues in chemical carcinogen-induced transformed human cells and human cancers. We found that histone H3 phosphorylation at Ser10 (p-H3S10) and Ser28 (p-H3S28) were up-regulated by 1...
December 20, 2016: Molecular Carcinogenesis
W Schlörmann, J Lamberty, S Lorkowski, D Ludwig, H Mothes, C Saupe, M Glei
Due to their beneficial nutritional profile the consumption of nuts contributes to a healthy diet and might reduce colon cancer risk. To get closer insights into potential mechanisms, the chemopreventive potential of different in vitro fermented nut varieties regarding the modulation of genes involved in detoxification (CAT, SOD2, GSTP1, GPx1) and cell cycle (p21, cyclin D2) as well as proliferation and apoptosis was examined in LT97 colon adenoma and primary epithelial colon cells. Fermentation supernatants (FS) of nuts significantly induced mRNA expression of CAT (up to 4...
December 20, 2016: Molecular Carcinogenesis
Panpan Zhan, Shihu Zhao, Hua Yan, Chunli Yin, Yi Xiao, Yunshan Wang, Ruoxuan Ni, Weiwen Chen, Guangwei Wei, Pengju Zhang
BACKGROUND: α-enolase (ENO1) plays pivotal roles in several types of cancer, but its clinical significance, functional role and possible mechanism in colorectal cancer (CRC) have remained unclear. METHODS: Expression level of ENO1 in CRC tissues was examined by qRT-PCR, Western blot and immunohistochemistry. The effects of ENO1 on cell growth were investigated by MTT, colony formation, flow cytometry assays and in vivo tumorigenic capacity analysis. The impacts of ENO1 on cell migration and invasion were also explored by scratch-healing, Transwell or Matrigel chamber assays and in vivo metastatic capacity analysis...
December 20, 2016: Molecular Carcinogenesis
Yan-Bo Zheng, Jian-Hua Gong, Xiu-Jun Liu, Yi Li, Yong-Su Zhen
CD13 is a marker of angiogenic endothelial cells, and recently it is proved to be a biomarker of human liver cancer stem cells (CSCs). Herein, the therapeutic effects of NGR-LDP-AE, a fusion protein composed of CD13-targeting peptide NGR and antitumor antibiotic lidamycin, on human liver cancer and its mechanism were studied. Western blot and immunofluorescence assay demonstrated that CD13 (WM15 epitope) was expressed in both human liver cancer cell lines and vascular endothelial cells, while absent in normal liver cells...
December 19, 2016: Molecular Carcinogenesis
Shuli Man, Jing Li, Peiyu Qiu, Jing Liu, Zhen Liu, Long Ma, Wenyuan Gao
Lung cancer is the foremost cause of cancer mortality and a growing economic burden worldwide. Rhizoma Paridis saponins (RPS) have been reported to exhibit potential anti-tumor effects on many kinds of tumor models. The present study was designed to investigate the mechanism-based chemopreventive nature of RPS against DEN-induced lung carcinogenesis in Kunming mice. As a result, the treatment with RPS reduced the severity of pulmonary histopathology. The mechanism of its antitumor effect involved in (a) reducing oxidative stress injury through up-regulating activities of CAT and SOD, (b) down-regulating the levels of inflammatory factors, like TNF-α, IL6, COX-2 and PGE2, (c) activation of caspase-3 and up-regulating the pro-apoptotic protein Bax, (d) decreasing the expression of PCNA, (e) depressing the expression of cancer stem cells marker CD133, (f) suppressing aberrant expression of cytokeratin 8 and 18, and (g) inhibiting EGFR/ PI3K/Akt, EGFR/Ras/Erk and NF-κB pathways...
December 19, 2016: Molecular Carcinogenesis
Shuo Chen, Zhi-Hong Zong, Dan-Dan Wu, Kai-Xuan Sun, Bo-Liang Liu, Yang Zhao
Metastasis-associated in colon cancer-1 (MACC1), has recently been identified as a key regulator in the progression of many cancers. However, its role in endometrial carcinoma (EC) remains unknown. MACC1 expression was determined in EC and normal endometrial tissues by immunohistochemistry. EC cell phenotypes and related molecules were examined after MACC1 downregulation by Small interfering RNA (siRNA) or microRNA (miRNA) transfection. We found that MACC1 was highly expressed in EC tissues than normal samples, and was significantly different in FIGO staging (I and II vs...
December 19, 2016: Molecular Carcinogenesis
Sierra N Quinn, Sarai H Graves, Clayton Dains-McGahee, Emilee M Friedman, Humma Hassan, Piotr Witkowski, Maria E Sabbatini
Pancreatic cancer is one of the most lethal human malignancies. A better understanding of the intracellular mechanism of migration and invasion is urgently needed to develop treatment that will suppress metastases and improve overall survival. Cyclic adenosine monophosphate (cyclic AMP) is a second messenger that has shown to regulate migration and invasion of pancreatic cancer cells. The rise of cyclic AMP suppressed migration and invasion of pancreatic ductal adenocarcinoma cells. Cyclic AMP is formed from cytosolic ATP by the enzyme adenylyl cyclase (AC)...
November 27, 2016: Molecular Carcinogenesis
Yi Liao, Jianguo Feng, Yi Zhang, Liling Tang, Shiyong Wu
UV induces CIRP expression and subsequent Stat3 activation, but the biological function and mechanism of CIRP and Stat3in mediating UVB-induced skin carcinogenesis have not been fully elucidated. In this study, we demonstrate that CIRP is elevated in all tested melanoma and non-melanoma skin cancer cell lines; and the expression of CIRP is upregulated in keratinocytes after being irradiated with relatively low dose (<5 mJ/cm(2) ), but not high dose (50 mJ/cm(2) ), UVB acutely and chronically. The increased expression of CIRP, either induced by UVB or through overexpression, leads to resistance of keratinocytes to UVB-induced growth arrest and death; and reduced expression of CIRP by RNA knockdown sensitizes keratinocyte cells to the low dose UVB radiation...
November 19, 2016: Molecular Carcinogenesis
Yuncheng Li, Erich M Sturgis, Lijun Zhu, Xiaoli Cao, Qingyi Wei, Hua Zhang, Guojun Li
Because E2F transcription factor 2 (E2F2) promoter polymorphisms have been implicated in carcinogenesis and prognosis, we investigated associations between genetic variants in five E2F2 promoter polymorphisms and recurrence risk of squamous cell carcinoma of the oropharynx (SCCOP) in 1 008 patients. A log-rank test and multivariable Cox models were used to assess the associations. Compared with patients with variant genotypes of E2F2-rs2742976 and E2F2-rs3218123, patients with common homozygous genotypes had better disease-free survival (both log-rank, P < 0...
November 19, 2016: Molecular Carcinogenesis
Abderrahim El Guerrab, Mahchid Bamdad, Yves-Jean Bignon, Frédérique Penault-Llorca, Corinne Aubel
Increased epidermal growth factor receptor (EGFR) expression in triple-negative breast cancer (TNBC) is recognized as a promising therapeutic target, specifically through the use of selective EGFR inhibitors combined with chemotherapies. TNBC is characterized by genetic instability that leads to increased sensitivity to cytotoxic agents. We analyzed the effect of anti-EGFR monoclonal antibodies (mAbs; cetuximab and panitumumab) in combination with chemotherapeutic agents (docetaxel, cisplatin and epirubicin) on EGFR-expressing TNBC cell lines that have different mutation statuses for one oncogene (KRAS) and two tumor suppressor genes (PTEN and BRCA1)...
November 19, 2016: Molecular Carcinogenesis
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