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Molecular Carcinogenesis

Joseph E Gergely, Armond E Dorsey, Goberdhan P Dimri, Manjari Dimri
Polycomb group (PcG) protein BMI1 is an important regulator of oncogenic phenotype and is often overexpressed in several human malignancies including breast cancer. Aberrant expression of BMI1 is associated with metastasis and poor prognosis in cancer patients. At present, therapy reagents that can efficiently inhibit the expression of BMI1 are not very well known. Here, we report that Timosaponin A-III (TA-III), a steroidal saponin obtained from the rhizomes of an herb, Anemarrhena asphodeloides, strongly inhibits expression of BMI1 in breast cancer cells...
March 12, 2018: Molecular Carcinogenesis
Cynthia C Jose, Lakshmanan Jagannathan, Vinay Singh Tanwar, Xiaoru Zhang, Chongzhi Zang, Suresh Cuddapah
Nickel (Ni) is an environmental and occupational carcinogen, and exposure to Ni is associated with lung and nasal cancers in humans. Furthermore, Ni exposure is implicated in several lung diseases including chronic inflammatory airway diseases, asthma and fibrosis. However, the mutagenic potential of Ni is low and does not correlate with its potent toxicity and carcinogenicity. Therefore, mechanisms underlying Ni exposure-associated diseases remain poorly understood. Since the health risks of environmental exposures often continue post exposure, understanding the exposure effects that persist after the termination of exposure could provide mechanistic insights into diseases...
March 12, 2018: Molecular Carcinogenesis
Jun Won Park, Min-Sik Kim, Dominic C Voon, Su-Jin Kim, Jingi Bae, Dong-Gi Mun, Seung-Ik Ko, Hark Kyun Kim, Sang-Won Lee, Dae-Yong Kim
The molecular mechanisms underlying the pathogenesis of diffuse-type gastric cancer (DGC) have not been adequately explored due to a scarcity of appropriate animal models. A recently developed tool well suited for this line of investigation is the Pdx-1-Cre;Cdh1F/+ ;Trp53F/F ;Smad4F/F (pChe PS) mouse model that spontaneously develops metastatic DGC showing nearly complete E-cadherin loss. Here, we performed a proteogenomic analysis to uncover the molecular changes induced by the concurrent targeting of E-cadherin, p53, and Smad4 loss...
March 12, 2018: Molecular Carcinogenesis
Peng Han, Hongliang Liu, Qiong Shi, Zhensheng Liu, Jesse D Troy, Walter T Lee, Jose P Zevallos, Guojun Li, Erich M Sturgis, Qingyi Wei
Squamous cell carcinoma of head and neck (SCCHN) is one of the most common malignancies worldwide, and nucleotide excision repair (NER) is involved in SCCHN susceptibility. In this analysis of 349 newly diagnosed SCCHN patients and 295 cancer-free controls, we investigated whether expression levels of eight core NER proteins were associated with risk of SCCHN. We quantified NER protein expression levels in cultured peripheral lymphocytes using a reverse-phase protein microarray. Compared with the controls, SCCHN patients had statistically significantly lower expression levels of ERCC3 and XPA (P = 0...
March 12, 2018: Molecular Carcinogenesis
Yuyang Sun, Anne Schaar, Pramod Sukumaran, Archana Dhasarathy, Brij B Singh
Growth factors, such as the transforming growth factor beta (TGFβ), play an important role in promoting metastasis of prostate cancer, thus understanding how TGFβ could induce prostate cancer cell migration may enable us to develop targeted strategies for advanced metastatic prostate cancer. To more clearly define the mechanism(s) involved in prostate cancer cell migration, we undertook a series of studies utilizing non-malignant prostate epithelial cells RWPE1 and prostate cancer DU145 and PC3 cells. Our studies show that increased cell migration was observed in prostate cancer cells, which was mediated through epithelial-to-mesenchymal transition (EMT)...
March 3, 2018: Molecular Carcinogenesis
Andrea Borrego, Wafa Hanna Koury Cabrera, José Ricardo Jensen, Mara Correa, Orlando Garcia Ribeiro, Nancy Starobinas, Marcelo De Franco, Angela Pettinicchio, Tommaso A Dragani, Olga Célia Martinez Ibañez, Giacomo Manenti
Somatic KRAS mutations are common in human lung adenocarcinomas and are associated with worse prognosis. In mice, Kras is frequently mutated in both spontaneous and experimentally induced lung tumors, although the pattern of mutation varies among strains, suggesting that such mutations are not random events. We tested if the occurrence of Kras mutations is under genetic control in two mouse intercrosses. Codon 61 mutations were prevalent, but the patterns of nucleotide changes differed between the intercrosses...
March 3, 2018: Molecular Carcinogenesis
Zixi Zhang, Junjun She, Jingyi Yang, Xin Bu, Gang Ji, Shaojun Zhu, Shuixiang He, Dake Chu
As a novel candidate tumor suppressor, NDRG4 is largely unstudied in human malignancies. In this study, we investigated the protein expression level of NDRG4 in gastric cancer and its association with outcome of patients. In the present study, we recruited 286 patients with gastric cancer and investigated the protein and mRNA expression of NDRG4 in cancer and adjacent normal specimens by immunohistochemistry assay and real-time PCR. The association of NDRG4 level with clinicopathological characteristics was investigated by appropriate statistical analysis...
March 3, 2018: Molecular Carcinogenesis
Yu Deng, Fulun Li, Pinglin He, Yafei Yang, Jin Yang, Yamei Zhang, Junying Liu, Yongping Tong, Qingfeng Li, Xian Mei, Zengyi Shu, Qi Zhao
Triptolide is an active component from a Chinese herb, Tripterygium wilfordii which has been applied for treating immune-related diseases over centuries. Recently, it was reported that a variety of cancer cell lines could be sensitized to DNA-damage based chemotherapy drugs in combination with Triptolide treatment. In the present study, we show that a short time exposure (3 hours) to Triptolide,which did not trigger apoptosis, could specifically increase breast cancer cells sensitivity to Doxorubicin rather than other chemotherapy drugs including Paclitaxel, Fluorouracil, and Mitomycin ...
March 3, 2018: Molecular Carcinogenesis
Zhi-Hui Zhang, Wei Zhang, Jing-Dong Zhou, Ting-Juan Zhang, Ji-Chun Ma, Zi-Jun Xu, Xin-Yue Lian, De-Hong Wu, Xiang-Mei Wen, Zhao-Qun Deng, Jiang Lin, Jun Qian
The present study was aimed to investigate SCIN expression as well as promoter methylation and further explore their clinical relevance in acute myeloid leukemia (AML) patients. Real-time quantitative PCR was carried out to detect the expression level of SCIN in 119 AML patients and 37 healthy controls. Real-time quantitative methylation-specific PCR and bisulfite sequencing PCR were carried out to detect SCIN promoter methylation levels in 103 AML patients and 29 controls. As compared with controls, the level of SCIN transcript was significantly down-regulated in AML patients (P = 0...
February 19, 2018: Molecular Carcinogenesis
Prashanta Kumar Panda, Prajna Paramita Naik, Prakash P Praharaj, Biswa Ranjan Meher, Piyush Kumar Gupta, Rama S Verma, Tapas K Maiti, Muthu K Shanmugam, Arunachalam Chinnathambi, Sulaiman Ali Alharbi, Gautam Sethi, Rajesh Agarwal, Sujit K Bhutia
Eradicating cancer stem cells (CSCs) in colorectal cancer (CRC) through differentiation therapy is a promising approach for cancer treatment. Our retrospective tumor-specimen analysis elucidated alteration in the expression of bone morphogenetic protein 2 (BMP-2) and β-catenin during the colon cancer progression, indicating that their possible intervention through "forced differentiation" in colon cancer remission. We reveal that Abrus agglutinin (AGG) induces the colon CSCs differentiation, enhancing sensitive to the anticancer therapeutics...
February 19, 2018: Molecular Carcinogenesis
Souvik Roy, Rituparna Das, Balaram Ghosh, Tania Chakraborty
Flavonoids are the most investigated phytochemicals due to their pharmacological and therapeutic activities. Their ability to chelate with metal ions has resulted in the emergence of a new category of molecules with a broader spectrum of pharmacological activities. In this study, the ruthenium quercetin complex has been synthesised and anticancer activity has been evaluated on a well-defined model of DMH followed by DSS induced rat colon cancer and on human colon cancer cell line HT-29. The characterizations accomplished through UV-visible, NMR, IR, Mass spectra and XRD techniques and antioxidant activity was assessed by DPPH, FRAP and ABTS methods...
February 14, 2018: Molecular Carcinogenesis
Yang Han, Chenlong Song, Jianying Wang, Huamei Tang, Zhihai Peng, Su Lu
5-FU-based chemotherapy is recently most recommended as the first-line treatment for gastric cancer (GC). However, 5-FU resistance is common for many postoperative GC patients. Homeobox A13 (HOXA13) is a member of homeobox genes highly expressed in many human tumors. Its potential roles and mechanisms of resistance to 5-FU in GC are poorly understood. In this study, we discovered that HOXA13 played an oncogenic role in vivo and in vitro. The patients with HOXA13 overexpression were closely related with poor prognosis and more prone to be resistant to 5-FU...
February 13, 2018: Molecular Carcinogenesis
Nosheen Akhtar, Deeba N Syed, Rahul K Lall, Bushra Mirza, Hasan Mukhtar
Epithelial-to-mesenchymal transition (EMT) plays a crucial role in prostate cancer (PCa) metastasis. This has led to a surge in the efforts for identification of safer and more effective compounds which can modulate EMT and consequently inhibiting migration and invasion of PCa cells. We reported previously that Plectranthoic acid (PA), a natural compound isolated from the extracts of Ficus microcarpa, has the capability to induce cell cycle arrest and apoptosis in PCa cells. Here, we determined the effects of PA on EMT, migration and invasion of PCa cells...
February 13, 2018: Molecular Carcinogenesis
Shanshan Qin, Jing Li, Yuan Si, Zhongwei He, Te Zhang, Dawei Wang, Xuewen Liu, Yang Guo, Liang Zhang, Shan Li, Qiang Li, Ying Liu
Cancerous inhibitor of protein phosphatase 2A (CIP2A) is a human oncoprotein that is overexpressed in multiple types of tumors and promotes the proliferation and transformation of cancer cells. However, whether CIP2A can be a new drug target for human glioblastoma multiforme (GBM) is largely unclear. In the present study, we demonstrated that the overexpression of CIP2A promotes invasive behavior in GBM, and a natural compound, cucurbitacin B (CuB), shows an anti-proliferative and anti-invasion effect in GBM cell lines...
February 2, 2018: Molecular Carcinogenesis
Ying-Chieh Su, Han Chang, Shih-Jung Sun, ChengYi Liao, Ling-Yi Wang, Jiunn-Lang Ko, Jinghua Tsai Chang
CX3CL1 is a unique chemokine, expressed in both soluble and membrane bound forms, which mediates different biological activities. Recent studies have revealed the potential of CX3CL1 signaling pathway as a target for the treatment of inflammation and cancer. The correlation between expression of CX3CL1 and prognosis of patients varies among cancers. In this study, based on CX3CL1 immunohistochemistry in non-small cell lung cancer, CX3CL1 levels were positively associated with cancer stage (Pearson chi-square, p = 0...
January 30, 2018: Molecular Carcinogenesis
Sha Oqiang Wang, Yuanda Cheng, Yang Gao, Zhiwei He, Wolong Zhou, Ruimin Chang, Zhenzi Peng, Yingying Zheng, Chaojun Duan, Chunfang Zhang
Lung adenocarcinoma (LADC), the most prevalent type of human lung cancer, is characterized by many molecular abnormalities. SH2B1, a member of the SH2-domain containing family, have recently been shown to act as tumor activators in multiple cancers, including LADC. However, the mechanisms underlying SH2B1 overexpression are not completely understood. Here, we reported that SH2B1 expression levels were significantly upregulated and positively associated with EMT markers and poor patient survival in LADC specimens...
January 30, 2018: Molecular Carcinogenesis
Tae Won Kim, Thomas Havighurst, KyungMann Kim, Mark Albertini, Yaohui G Xu, Vladimir S Spiegelman
Melanoma is one of the deadliest forms of skin cancer. Although BRAF inhibitors significantly enhance survival of metastatic melanoma patients, most patients relapse after less than a year of treatment. We previously reported that mRNA binding protein Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) is overexpressed in metastatic melanoma and that expression of IGF2BP1 confers resistance to chemotherapeutic agents. Here we demonstrate that IGF2BP1 plays an important role in the sensitivity of melanoma to targeted therapy...
January 25, 2018: Molecular Carcinogenesis
Ashley M Poenitzsch Strong, Scott M Berry, David J Beebe, Jian-Liang Li, Vladimir S Spiegelman
MicroRNAs (miRNAs), small 22-25 nucleotide non-coding RNAs, play important roles in cellular and tumor biology. However, characterizing miRNA function remains challenging due to an abundance of predicted targets and an experimental bottleneck in identifying biologically relevant direct targets. Here we developed a novel technique (miFAST) to identify direct miRNA target genes. Using miFAST, we confirmed several previously reported miR-340 target genes and identified five additional novel direct miR-340 targets in melanoma cells...
January 19, 2018: Molecular Carcinogenesis
Simon C Baker, Volker M Arlt, Radek Indra, Madeleine Joel, Marie Stiborova, Ian Eardley, Niaz Ahmad, Wolfgang Otto, Maximilian Burger, Peter Rubenwolf, David H Phillips, Jennifer Southgate
Extra-hepatic metabolism of xenobiotics by epithelial tissues has evolved as a self-defence mechanism but has potential to contribute to the local activation of carcinogens. Bladder epithelium (urothelium) is bathed in excreted urinary toxicants and pro-carcinogens. This study reveals how differentiation affects cytochrome P450 (CYP) activity and the role of NADPH:P450 oxidoreductase (POR). CYP1A1 and CYP1B1 transcripts were inducible in normal human urothelial (NHU) cells maintained in both undifferentiated and functional barrier-forming differentiated states in vitro...
January 11, 2018: Molecular Carcinogenesis
Bharat Thyagarajan, Weihua Guan, Veronika Fedirko, Helene Barcelo, Ramya Ramasubramaian, Myron Gross, Michael Goodman, Roberd M Bostick
Somatic mutations in mitochondrial DNA have been reported in colorectal adenomatous polyps (adenomas), the precursors to most colorectal cancers. However, there are no reports of associations of germline variation in mitochondrial DNA with adenoma risk. We investigated associations of germline polymorphisms in the displacement loop (D-loop) and non-D-loop region of the mitochondrial genome with incident, sporadic colorectal adenoma in three pooled colonoscopy-based case-control studies (n = 327 adenoma cases, 420 controls) that used identical methods for case and risk factor ascertainment...
January 11, 2018: Molecular Carcinogenesis
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