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Molecular Carcinogenesis

Phuong N Le, Stephen B Keysar, Bettina Miller, Justin R Eagles, Tugs-Saikhan Chimed, Julie Reisinger, Karina E Gomez, Cera Nieto, Brian C Jackson, Hilary L Somerset, J Jason Morton, Xiao-Jing Wang, Antonio Jimeno
Wnt pathway activation maintains the cancer stem cell (CSC) phenotype and promotes tumor progression, making it an attractive target for anti-cancer therapy. Wnt signaling at the tumor and tumor microenvironment (TME) front have not been investigated in depth in head and neck squamous cell carcinoma (HNSCC). In a cohort of 48 HNSCCs, increased Wnt signaling, including Wnt genes (AXIN2, LGR6, WISP1) and stem cell factors (RET, SOX5, KIT), were associated with a more advanced clinical stage. Key Wnt pathway proteins were most abundant at the cancer epithelial-stromal boundary...
October 31, 2018: Molecular Carcinogenesis
Jung Min Song, Jintaek Im, Richard Seonghun Nho, Yong Hwan Han, Pramod Upadhyaya, Fekadu Kassie
Although members of the hyaluronan (HA)-CD44/HA-mediated motility receptor (RHAMM) signaling pathway have been shown to be overexpressed in lung cancer, their role in lung tumorigenesis is unclear. In the present study, we first determined levels of HA and its receptors CD44 and RHAMM in human non-small cell lung cancer (NSCLC) cells and stromal cells as well as mouse lung tumors. Subsequently, we examined the role of HA-CD44/RHAMM signaling pathway in mediating the proliferation and survival of NSCLC cells and the cross-talk between NSCLC cells and normal human lung fibroblasts (NHLFs)/lung cancer-associated fibroblasts (LCAFs)...
October 26, 2018: Molecular Carcinogenesis
Jessica A Zavadil, Maryanne C S Herzig, Kim Hildreth, Amir Foroushani, William Boswell, Ronald Walter, Robert Reddick, Hugh White, Habil Zare, Christi A Walter
Hepatocellular carcinoma (HCC) remains a deadly cancer, underscoring the need for relevant preclinical models. Male C3HeB/FeJ mice model spontaneous HCC with some hepatocarcinogenesis susceptibility loci corresponding to syntenic regions of human chromosomes altered in HCC. We tested other properties of C3HeB/FeJ tumors for similarity to human HCC. C3HeB/FeJ tumors were grossly visible at 4 months of age, with prevalence and size increasing until about 11 months of age. Histologic features shared with human HCC include hepatosteatosis, tumor progression from dysplasia to poorly differentiated, vascular invasion, and trabecular, oncocytic, vacuolar, and clear cell variants...
October 26, 2018: Molecular Carcinogenesis
Jun Zhang, YuanYuan Pei, Wen Yang, WenXiu Yang, Boxin Chen, Xing Zhao, Shiqi Long
Cancer stem cells (CSCs) account for tumor self-renewal and heterogeneity. Oxidative-nitrosative stress (ONS) is an independent etiologic factor throughout tumorigenesis. Emerging evidences indicated that the interaction of ONS with CSCs contributes to tumor progression and resistance to chemoradiotherapy. Cytoglobin (Cygb) is a member of human hexacoordinate haemoglobin family and acts as a dynamic mediator of redox homeostasis. We observed that Cygb is significantly deregulated in human hepatocellular carcinoma (HCC) tissue and its decrease aggravates the growth of liver cancer stem cells (LCSCs) and increases the subpopulation of CD133(+) LCSCs...
October 26, 2018: Molecular Carcinogenesis
Basudeb Das, Jyoti Roy, Neha Jain, Bibekanand Mallick
P-Element induced wimpy testis (PIWI)-interacting RNAs (piRNAs) are a promising class of small regulatory RNAs, earlier believed to control transposable elements (TEs) activity in germlines are now reported in somatic and cancer cells. The aberrant expression of piRNAs has been documented in various cancers wherein they modulate tumorigenesis either as oncogenes or tumor suppressors by curbing target gene expression. However, there is no report yet on the association of piRNAs in fibrosarcoma, an early metastatic lethal tumor...
October 26, 2018: Molecular Carcinogenesis
Ming Jian, Zhu Yunjia, Ding Zhiying, Jiang Yanduo, Jiang Guocheng
Interleukin-7(IL-7) can regulate proliferation and apoptosis of cell and also regulate tumor lymphangiogenesis, but whether it regulating autophagy of tumor cells is not well known. We study the relationship between IL-7 and some autophagy-related markers, Beclin 1 and mammalian target of rapamycin (mTOR) and the mechanism of IL-7 in regulating autophagy of human lung cancer cells. We detected expression of Beclin 1 and mTOR in lung cancer cells and their impact on the prognosis of lung cancer patients. Using Western Blot and Reverse Transcription PCR, we found that IL-7 activates PI3K/Akt/mTOR signaling pathway by downregulated the expression of Beclin 1 in lung cancer cell lines...
October 26, 2018: Molecular Carcinogenesis
Xiao-Jing Chen, Sha Wu, Rui-Ming Yan, Liang-Sheng Fan, Lan Yu, Yan-Mei Zhang, Wen-Fei Wei, Chen-Fei Zhou, Xiang-Guang Wu, Mei Zhong, Yan-Hong Yu, Li Liang, Wei Wang
AIM: To explore the mechanisms through which hypoxic tumor microenvironment (TME) modulates the transition of tumor-associated macrophages (TAMs). METHODS: The migration ability of RAW264.7 macrophages was determined by transwell assay. Flow cytometric, western blot and immunofluorescence analyses of CD206 further validated the M2 polarization of macrophages. Immunofluorescence, western blot and qRT-PCR were performed to detect the expression of neuropilin-1 (Nrp-1) and carbonic anhydrase IX (CAIX)...
October 26, 2018: Molecular Carcinogenesis
Runzhou Zhuang, Xuanyu Zhang, Di Lu, Jianguo Wang, Jianyong Zhuo, Xuyong Wei, Qi Ling, Haiyang Xie, Shusen Zheng, Xiao Xu
Accumulating evidence indicates that long non-coding RNAs (lncRNAs) play a crucial role in hepatocellular carcinoma (HCC). Here, we reported a novel lncRNA, CTC-505O3 (lncRNA DRHC), that was downregulated in HCC and its low expression was associated with dismal survival. Gain-of-function studies indicated that it inhibited proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) in HCC cell lines in vitro. lncRNA DRHC also inhibited tumorigenicity in vivo. In mechanistic experiments, GO analysis based on NGS indicated that MAPK signaling was most affected...
October 26, 2018: Molecular Carcinogenesis
James Lawson, Christopher Dickman, Rebecca Towle, James Jabalee, Ariana Rani, Cathie Garnis
Extracellular vesicles (EVs) are mediators of communication between cancer cells and the surrounding tumor microenvironment. EV content is able to influence key tumorigenic changes including invasion, metastasis, and inducing pro-tumor changes in the stroma. MiR-142-3p is a known tumor suppressor in LAC and was recently shown to be enriched within LAC EVs, indicating its potential as a key signaling miRNA. Our research demonstrates the role EV associated miR-142-3p plays when transferred from LAC cells to both endothelial and fibroblast cells...
October 26, 2018: Molecular Carcinogenesis
Lisa Tremmel, Okkyung Rho, Thomas J Slaga, John DiGiovanni
Prevention remains an important strategy to reduce the burden of cancer. One approach to prevent cancer is the use of phytochemicals in various combinations as safe and effective cancer preventative agents. The purpose of this study was to examine the effects of the combination of ursolic acid (UA) and curcumin (Curc) for potential combinatorial inhibition of skin tumor promotion using the mouse two-stage skin carcinogenesis model. In short-term experiments, the combination of UA + Curc given topically prior to 12-O-tetradecanoylphorbol-13-acetate (TPA) significantly inhibited activation of epidermal EGFR, p70S6K, NF-κB p50, Src, c-Jun, Rb, and IκBα...
October 22, 2018: Molecular Carcinogenesis
Jianwei Lin, Yuchen Hou, Shanzhou Huang, Ziming Wang, Chengjun Sun, Zekang Wang, Xiaoshun He, Nga Lei Tam, Chenglin Wu, Linwei Wu
Exportin-T (XPOT) belongs to the RAN-GTPase exportin family that mediates export of tRNA from the nucleus to the cytoplasm. Up-regulation of XPOT indicates poor prognosis in breast cancer patients. However, the correlation between XPOT and hepatocellular carcinoma (HCC) remains unclear. Here, we found that high expression of XPOT in HCC indicated worse prognosis via bioinformatics analysis. Consistently, immunohistochemical staining of 95 pairs of tumors and adjacent normal liver tissues (ANLT) also showed up-regulation of XPOT...
October 18, 2018: Molecular Carcinogenesis
Chun-Nan Yeh, Ming-Huang Chen, Yu-Chan Chang, Ren-Chin Wu, Lee-Cheng Tsao, Shang-Yu Wang, Chi-Tung Cheng, Kun-Chun Chiang, Tsung-Wen Chen, Michael Hsiao, Wen-Hui Weng
PURPOSE: Cholangiocarcinoma (CCA) is a devastating disease with very poor prognosis due to late diagnosis and resistance to traditional chemotherapies and radiotherapies. Herein, thioacetamide (TAA)-induced rat CCA model and CGCCA cell line were used; we aim to study the cytogenetic features during tumoral development of CCA and uncover the mystery regarding carcinogenesis of CCA. METHODS: The Array comparative genomic hybridization analysis, in silico method, gene knockdown, western blot, cell count proliferation assay, clonogenecity assay, and IHC staining were applied in this study...
October 18, 2018: Molecular Carcinogenesis
Yanle Ye, Feng Zhang, Qingxia Chen, Zhiyang Huang, Meijun Li
This investigation was purposed to extrapolate whether and how lncRNA MALAT1, miR-194-5p, and ACVR2B altered development of clear cell kidney carcinoma (KIRC). We totally gathered 318 pairs of KIRC tissues and adjacent normal tissues, and also purchased human KIRC cell lines and normal human proximal tubular epithelial cell line. Besides, si-MALAT1, pcDNA-MALAT1, miR-194-5p mimic, miR-194-5p inhibitor, and negative control (NC) were, respectively, transfected into KIRC cells. The viability, proliferation, and apoptosis of the cells were determined with CCK-8 assay, colony formation assay, and flow cytometry...
October 18, 2018: Molecular Carcinogenesis
Xiaofeng Li, Qiang Fu, Yanjia Zhu, Jian Wang, Jianjing Liu, Xiaozhou Yu, Wengui Xu
The aim of this study is to investigate the role of CD147 in glucose metabolic regulation and its association with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) treatment sensitivity prediction using 18 F-fluorodeoxyglucose (18 F-FDG) PET/CT imaging in non-small cell lung cancer (NSCLC). In this study, four human NSCLC cell lines with different EGFR-TKI responses were used to detect p-EGFR/EGFR and CD147 expression via Western blotting and flow cytometric analyses. Radioactive uptake of 18 F-FDG by established stable NSCLC cell lines (HCC827, H1975) with different levels of CD147 expression and the corresponding xenografts was assessed through γ-radioimmunoassays in vitro and micro-PET/CT imaging in vivo to study the role of CD147 in glucose metabolic reprogramming...
October 15, 2018: Molecular Carcinogenesis
Veselina Zhivkova, Felix Kiecker, Peter Langer, Jürgen Eberle
Melanoma represents a prime example demonstrating the success of targeted therapy in cancer. Nevertheless, it remained a deadly disease until now, and the identification of new, independent strategies as well as the understanding of their molecular mechanisms may help to finally overcome the high mortality. Both indirubins and TNF-related apoptosis-inducing ligand (TRAIL) represent promising candidates. Here, the indirubin derivative DKP-073 is shown to trigger apoptosis in melanoma cells, which is enhanced by the combination with TRAIL and is accompanied by complete loss of cell viability...
October 15, 2018: Molecular Carcinogenesis
Yoshinobu Saitoh, Costansia Bureta, Hiromi Sasaki, Satoshi Nagano, Shingo Maeda, Tatsuhiko Furukawa, Noboru Taniguchi, Takao Setoguchi
Undifferentiated pleomorphic sarcoma (UPS) is the second most frequent soft tissue sarcoma. Because of its resistance to chemotherapy, UPS patients are treated with surgical resection and complementary radiotherapy. However, since standard chemotherapy has not been established, unresectable or metastatic cases result in a poor prognosis. Therefore, the identification of a more effective therapy for UPS patients is needed. The development and progression of malignant tumors involve epigenetic alterations, and histone deacetylases (HDAC) have become a promising chemotherapeutic target...
October 10, 2018: Molecular Carcinogenesis
Anna M Mancha-Ramirez, Xiaoyu Yang, Huiyun Liang, Jacob Junco, Kevin P Lee, Sarah F Bovio, Maricruz Espinoza, Julia Wool, Andrew Slaga, Daniel C Glade, Martha Hanes, Gunjan Malik, Dae Joon Kim, John DiGiovanni, Thomas J Slaga
Despite effective surgical methods for non-melanoma skin cancer (NMSC), patients suffer from tissue damage, scarring, or even disfigurement; thus, there is a need for chemopreventive approaches. Because of the complex interplay between glucocorticoids (GCs), inflammation, and cancer, we sought to determine the role of 11β-hydroxysteroid dehydrogenase 1 and 2 (11βHSD1 and 2) in regulating GCs during skin cancer development and progression. 11βHSDs modulate the activation of GCs in a tissue-specific manner and have been reported to play a role in development and progression of other types of cancer, but their role has not yet been reported in NMSC...
October 9, 2018: Molecular Carcinogenesis
Hai Li, Shikuo Rong, Chao Chen, Yayun Fan, Tuo Chen, Yong Wang, Dongmei Chen, Chun Yang, Jiali Yang
Human C-X-C Motif Chemokine Receptor 3A (CXCR3A) and CXCR3B are two splice variants of CXCR3 that is involved in a variety of progressive processes of cancer cells, including proliferation, migration, invasion, and tumorigenicity. However, the molecular mechanisms of CXCR3 in colorectal cancer (CRC) remain incomplete understood. In the present study, a significantly up-regulated CXCR3 protein was firstly observed in CRC tissues and cell lines in comparison with the paired non-tumor tissues and normal intestinal epithelial cells, which was positively associated with CRC TNM stages...
October 9, 2018: Molecular Carcinogenesis
Vidya Gopalakrishnan, Sumedha Dahal, Gudapureddy Radha, Shivangi Sharma, Sathees C Raghavan, Bibha Choudhary
Efficient DNA repair is indispensable for maintaining genomic integrity in humans. Cancer associated deletions and mutations are mainly due to misrepaired DNA double-strand breaks (DSBs). Classical nonhomologous end joining (c-NHEJ) and homologous recombination (HR) are two major DSB repair pathways in humans. An error prone, alternative NHEJ pathway that utilizes microhomology was also reported in cancer cells and to a lesser extent in normal cells. In the present study, we evaluated the efficiency of various DSB repair pathways in the most common lymphoma, the diffuse large B cell lymphoma (DLBCL)...
October 9, 2018: Molecular Carcinogenesis
Michael A Gordon, Beatrice Babbs, Dawn R Cochrane, Benjamin G Bitler, Jennifer K Richer
Ovarian cancer metastasizes via direct seeding, whereby cancer cells shed from the primary site, resist cell death in the peritoneal cavity, then metastasize to peritoneal organs. We sought to identify molecular mechanisms that facilitate ovarian cancer cell anchorage independent survival. Gene expression profiling was performed on ovarian cancer cells grown in attached or forced suspension culture and confirmed by RT-qPCR. Anoikis was measured by Caspase 3/7 assay. Since the long non-coding RNA Metastasis Associated Lung Adenocarcinoma transcript 1 (MALAT1) was among the transcripts most highly increased in forced suspension culture, modified anti-sense oligonucleotides (ASO) were used to inhibit its expression...
October 8, 2018: Molecular Carcinogenesis
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