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Molecular Carcinogenesis

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https://www.readbyqxmd.com/read/28621442/dendritic-cell-based-immunotherapy-evokes-potent-anti-tumor-immune-responses-in-cd105-human-renal-cancer-stem-cells
#1
Xiao-Fei Zhang, De-Sheng Weng, Ke Pan, Zi-Qi Zhou, Qiu-Zhong Pan, Jing-Jing Zhao, Yan Tang, Shan-Shan Jiang, Chang-Long Chen, Yong-Qiang Li, Hong-Xia Zhang, Alfred E Chang, Max S Wicha, Yi-Xin Zeng, Qiao Li, Jian-Chuan Xia
Cancer stem cells (CSCs) are responsible for tumor initiation, progression, and resistance to therapeutic agents; they are usually less sensitive to conventional cancer therapies, and could cause tumor relapse. An ideal therapeutic strategy would therefore be to selectively target and destroy CSCs, thereby preventing tumor relapse. The aim of the present study was to evaluate the effectiveness of dendritic cells (DCs) pulsed with antigen derived from CD105+ human renal cell carcinoma(RCC) CSCs against renal cancer cells in vitro and in vivo...
June 16, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28618116/differences-in-p53-status-significantly-influence-the-cellular-response-and-cell-survival-to-1-25-dihydroxyvitamin-d3-metformin-cotreatment-in-colorectal-cancer-cells
#2
Mohamed A Abu El Maaty, Wendy Strassburger, Tooba Qaiser, Yasamin Dabiri, Stefan Wölfl
Mutations in the tumor suppressor p53 are highly prevalent in cancers and are known to influence the sensitivity of cells to various chemotherapeutics including the anti-cancer candidates 1,25-dihydrovitamin D3 [1,25D3] and metformin. Previous studies have demonstrated additive/synergistic anti-cancer effects of the 1,25D3-metformin combination in different models, however the influence of p53 status on the efficacy of this regimen has not been investigated. The CRC cell lines HCT116 wild-type (wt), HCT116 p53-/- and HT-29 (mutant; R273H) were employed, covering 3 different p53 variations...
June 15, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28618103/secretory-pathway-ca-2-atpases-promote-in-vitro-microcalcifications-in-breast-cancer-cells
#3
Donna Dang, Hari Prasad, Rajini Rao
Calcification of the breast is often an outward manifestation of underlying molecular changes that drive carcinogenesis. Up to 50% of all non-palpable breast tumors and 90% of ductal carcinoma in situ present with radiographically dense mineralization in mammographic scans. However, surprisingly little is known about the molecular pathways that lead to microcalcifications in the breast. Here, we report on a rapid and quantitative in vitro assay to monitor microcalcifications in breast cancer cell lines, including MCF7, MDA-MB-231 and Hs578T...
June 15, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28618089/crh-promotes-human-colon-cancer-cell-proliferation-via-il-6-jak2-stat3-signaling-pathway-and-vegf-induced-tumor-angiogenesis
#4
Xianjun Fang, Yali Hong, Li Dai, Yuanyuan Qian, Chao Zhu, Biao Wu, Shengnan Li
Corticotrophin-releasing hormone (CRH) has been demonstrated to participate in various diseases. Our previous study showed that its receptor CRHR1 mediated the development of colitis-associated cancer in mouse model. However, the detailed mechanisms remain unclear. In this study, we explored the oncogenetic role of CRH/CRHR1 signaling in colon cancer cells. Cell proliferation and colony formation assays revealed that CRH contributed to cell proliferation. Moreover, tube formation assay showed that CRH-treated colon cancer cell supernatant significantly promoted tube formation of human umbilical vein endothelial cells (HUVECs)...
June 15, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28618084/ccl20-promotes-migration-and-invasiveness-of-human-cancerous-breast-epithelial-cells-in-primary-culture
#5
Antonella Muscella, Carla Vetrugno, Santo Marsigliante
The relation between the tumor and its microenvironment is one of the most interesting and less understood issues. Recently, we showed a role of CCL20 chemokine in proning the healthy tissue neighbouring the tumor to carcinogenesis. Besides, tumor-secreted CCL20 induced proliferation, migration and EMT of healthy cells. In this context, we have studied here if CCL20 had effects on the migration of cancer cells and the intracellular pathways used in breast epithelial cells in primary culture. Using molecular (siRNA) and pharmacological (inhibitors) techniques, we found multiple signaling kinases to be activated and involved in CCL20-induced tumor breast cell migration...
June 15, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28618017/curcumin-and-metformin-mediated-chemoprevention-of-oral-cancer-is-associated-with-inhibition-of-cancer-stem-cells
#6
Gangotri Siddappa, Safeena Kulsum, Doddathimmasandra Ramanjanappa Ravindra, Vinay V Kumar, Nalini Raju, Nisheena Raghavan, Holalugunda Vittalamurthy Sudheendra, Anupam Sharma, Sumsum P Sunny, Tina Jacob, Binu T Kuruvilla, Merina Benny, Benny Antony, Mukund Seshadri, Padma Lakshminarayan, Wesley Hicks, Amritha Suresh, Moni A Kuriakose
Effective chemoprevention is critical for improving outcomes of oral cancer. As single agents, curcumin and metformin, are reported to exhibit chemopreventive properties, in vitro as well as in patients with oral cancer. In this study, the chemopreventive efficacy of this drug combination was tested in a 4NQO (4-nitro-quinoline-oxide) induced, mice oral carcinogenesis model. Molecular analysis revealed a cancer stem cell (CSC)-driven, oral carcinogenic progression in this model, wherein a progressive increase in the expression of CSC-specific markers (CD44 and CD133) was observed from 8th to 25th week, at transcript (40 to 100 fold) and protein levels (p≤0...
June 15, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28618012/metabolomic-signature-of-brain-cancer
#7
Renu Pandey, Laura Caflisch, Alessia Lodi, Andrew J Brenner, Stefano Tiziani
Despite advances in surgery and adjuvant therapy, brain tumours represent one of the leading causes of cancer-related mortality and morbidity in both adults and children. Gliomas constitute about 60% of all cerebral tumours, showing varying degrees of malignancy. They are difficult to treat due to dismal prognosis and limited therapeutics. Metabolomics is the untargeted and targeted analyses of endogenous and exogenous small molecules, which characterizes the phenotype of an individual. This emerging "omics" science provides functional readouts of cellular activity that contribute greatly to the understanding of cancer biology including brain tumour biology...
June 15, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28577326/trivalent-chromium-induces-autophagy-by-activating-sphingomyelin-phosphodiesterase-2-and-increasing-cellular-ceramide-levels-in-renal-hk2-cells
#8
Cheng-Lin Yang, Shiow-Her Chiou, Wei-Chun Tai, Nithila A Joseph, Kuan-Chih Chow
In this study, we examined the role of autophagy in the initiation of lipid increases in renal epithelial HK2 cells. We found that trivalent chromium [Cr(III)] induced autophagy by activating sphingomyelin phosphodiesterase 2 (SMPD2). SMPD2 increases levels of ceramide and other lipids. Confocal immunofluorescence microscopy showed that signals of ceramide overlapped with LC3, suggesting that ceramide might play an important role in the formation of autophagosome. In conclusion, our data indicate that Cr(III) induces autophagy via structural aberration of organelle membrane, in particular by the increase of lipid compositions in addition to autophagy-associated proteins...
June 3, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28574654/neuroprotective-effects-respond-to-cerebral-ischemia-without-susceptibility-to-hb-tumorigenesis-in-vhl-heterozygous-knockout-mice
#9
Ying Wang, Jingyun Yang, Guhong Du, Dexuan Ma, Liangfu Zhou
The von Hippel-Lindau (VHL) tumor suppressor gene plays a prominent role in the development of hemangioblastomas (HBs) within specific regions of the human' central nervous system (CNS). Alterations in VHL gene are rarely observed in the more common features of human VHL-related tumors in animal models, and VHL heterozygous knockout (VHL + / -) mice do not develop HBs. We tested whether VHL heterozygous knockout mice exhibited genetic predisposition to the development of HBs and conferred a selective advantage involving growth of blood vessels to its carrier...
June 2, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28574619/ucp2-upregulation-promotes-plc%C3%AE-1-signaling-during-skin-cell-transformation
#10
Annapoorna Sreedhar, Julia Lefort, Petra Petruska, Xin Gu, Runhua Shi, Sumitra Miriyala, Manikandan Panchatcharam, Yunfeng Zhao
Uncoupling protein 2 (UCP2), whose physiological role is to decrease mitochondrial membrane potential and reactive oxygen species (ROS) production, is often overexpressed in human cancers. UCP2 upregulation has recently been proposed as a novel survival mechanism for cancer cells. However, until now, how exactly UCP2 promotes tumorigenesis remains inconclusive. Based on a widely used skin cell transformation model, our data demonstrated that UCP2 differentially regulated ROS. UCP2 upregulation decreased superoxide whereas it increased hydrogen peroxide production with concomitant increase in the expression and activity of manganese superoxide dismutase (MnSOD), the primary mitochondrial antioxidant enzyme...
June 2, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28574613/senp2-suppresses-epithelial-mesenchymal-transition-of-bladder-cancer-cells-through-desumoylation-of-tgf-%C3%AE-ri
#11
Mingyue Tan, Dingguo Zhang, Encheng Zhang, Dongliang Xu, Zhihong Liu, Jianxin Qiu, Yu Fan, Bing Shen
SUMO-specific protease 2 (SENP2) is a deSUMOylation protease that plays an important role in the regulation of transforming growth factor-β (TGF-β) signaling. Aberrant TGF-β signaling is common in human cancers and contributes to tumor metastasis by inducing an epithelial-mesenchymal transition (EMT). In previous studies, we demonstrated that SENP2 suppresses bladder cancer cell migration and invasion. However, little is known about whether SENP2 inhibits EMT by regulating TGF-β signaling in bladder cancer progression...
June 2, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28574612/basal-cell-carcinoma-pathogenesis-and-therapy-involving-hedgehog-signaling-and-beyond
#12
Anshika Bakshi, Sandeep C Chaudhary, Mehtab Rana, Craig A Elmets, Mohammad Athar
Basal cell carcinoma (BCC) of the skin is driven by aberrant hedgehog signaling. Thus blocking this signaling pathway by small molecules such as vismodegib inhibits tumor growth. Primary cilium in the epidermal cells plays an integral role in the processing of hedgehog signaling related proteins. Recent genomic studies point to the involvement of additional genetic mutations that might be associated with the development of BCCs, suggesting significance of other signaling pathways, such as WNT, NOTCH, mTOR, and Hippo, aside from hedgehog in the pathogenesis of this human neoplasm...
June 2, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28574600/diallyl-trisulfides-a-natural-histone-deacetylase-inhibitor-attenuate-hif-1%C3%AE-synthesis-and-decreases-breast-cancer-metastasis
#13
Zhonghong Wei, Yunlong Shan, Li Tao, Yuping Liu, Zhijie Zhu, Zhaoguo Liu, Yuanyuan Wu, Wenxing Chen, Aiyun Wang, Yin Lu
Intratumoral hypoxia promotes the distant metastasis of cancer subclones. The clinical expression level of hypoxia-inducible factor-1α (HIF-1α) reflects the prognosis of a variety of cancers, especially breast cancer. Histone deacetylase (HDAC) inhibitors can target HIF-1α protein due to von Hippel-Lindau protein-dependent degradation. Dietary organosulfur compounds, such as those in garlic, have been reported as HDAC inhibitors. The effects of diallyl sulfide (DAS), diallyl disulfide (DADS) and diallyl trisulfide (DATS) on the ratio of firefly/Renilla luciferase activity in hypoxic MDA-MB-231 cells were determined...
June 2, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28574599/inhibition-of-glycogen-synthase-kinase-3-beta-gsk3%C3%AE-suppresses-the-progression-of-esophageal-squamous-cell-carcinoma-by-modifying-stat3-activity
#14
Shegan Gao, Shuoguo Li, Xiaoxian Duan, Zhen Gu, Zhikun Ma, Xiang Yuan, Xiaoshan Feng, Huizhi Wang
While GSK3β has been reported to have contrasting effects on the progression of different tumors, its possible functions in esophageal squamous cell carcinoma (ESCC) and the related molecular mechanisms remain unknown. Here, we investigated the expression, function, and molecular mechanism of GSK3β in the development of ESCC in vitro and in vivo. Though the expression of total GSK3β was significantly increased, the phosphorylated (inactivated) form of GSK3β (Ser9) was concurrently decreased in the cancerous tissues of patients with ESCC compared with controls, suggesting that GSK3β activity was enhanced in cancerous tissues...
June 2, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28543447/fas-signaling-induces-stemness-properties-in-colorectal-cancer-by-regulation-of-bmi1
#15
Jiaxuan Chen, Yadong Wang, Linghao Zhuo, Zhizhong Liu, Tao Liu, Wenjing Li, Yidong Cai, Haoxuan Zheng
Fas signaling promotes colorectal cancer (CRC) metastasis by inducing epithelial- mesenchymal transition (EMT). The acquisition of EMT properties in turn induces stemness but the mechanism by which Fas signaling contributes to it still remains unclear. Hence, the aim of this study was to investigate how Fas signaling regulates CRC stemness. For this purpose, soft agar assay, sphere formation assay, cell survival analysis, immunoblot, qRT-PCR, chromatin immunoprecipitation, and luciferase reporter assay were performed...
May 25, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28544328/acetylcholine-related-proteins-in-non-neoplastic-appearing-colonic-mucosa-from-patients-with-colorectal-neoplasia
#16
Morten Matthiesen Bach Damm, Thorbjørn Søren Rønn Jensen, Badar Mahmood, Morten Lundh, Steen Seier Poulsen, Niels Bindslev, Mark Berner Hansen
The pathogenesis of colorectal neoplasia (CRN) has been associated with altered non-neuronal acetylcholine (ACh) metabolism. The aim of this study was to characterize expression, function, and cellular location of ACh-related proteins in biopsies obtained from endoscopic normal-appearing sigmoid colon in patients with and without CRN. Messenger-RNA (mRNA) levels of 17 ACh-related proteins were quantified by rt-qPCR. Functional responses to ACh, measured as electrogenic transepithelial short circuit current (SCC), were recorded using the Ussing chamber technique...
May 23, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28544176/interactions-between-calcium-intake-and-polymorphisms-in-genes-essential-for-calcium-reabsorption-and-risk-of-colorectal-neoplasia-in-a-two-phase-study
#17
Jing Zhao, Xiangzhu Zhu, Martha J Shrubsole, Reid M Ness, Elizabeth A Hibler, Qiuyin Cai, Jirong Long, Zhi Chen, Ming Jiang, Edmond K Kabagambe, Bing Zhang, Lifang Hou, Walter E Smalley, Todd L Edwards, Edward L Giovannucci, Wei Zheng, Qi Dai
The SLC8A1 (solute carrier family 8, member 1) gene, encoding Na(+) /Ca(2+) exchanger, is essential in regulating calcium reabsorption and homeostasis. Calcium homeostasis plays a key role in cell proliferation and apoptosis. We hypothesized that polymorphisms in five calcium-regulating genes (SLC8A1, ATP2B1, CALB1, CALB2, and CABP1) interact with calcium intake in relation to the risk of colorectal neoplasia. A two-phase (discovery and replication) study was conducted within the Tennessee Colorectal Polyp Study, including a total of 1275 cases and 2811 controls...
May 23, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28544069/cd38-enhances-the-proliferation-and-inhibits-the-apoptosis-of-cervical-cancer-cells-by-affecting-the-mitochondria-functions
#18
Shan Liao, Songshu Xiao, Hongxiang Chen, Manying Zhang, Zhifang Chen, Yuehua Long, Lu Gao, Guangchao Zhu, Junyu He, Shuping Peng, Wei Xiong, Zhaoyang Zeng, Zheng Li, Ming Zhou, Xiaoling Li, Jian Ma, Minghua Wu, Juanjuan Xiang, Guiyuan Li, Yanhong Zhou
Cervical cancer is one of the most common malignant tumors in women all over the world. The exact mechanism of occurrence and development of cervical cancer has not been fully elucidated. CD38 is a type II transmembrane glycoprotein, which was found to mediate diverse activities, including signal transduction, cell adhesion, and cyclic ADP-ribose synthesis. Here, we reported that CD38 promoted cell proliferation and inhibited cell apoptosis in cervical cancer cells by affecting the mitochondria functions. We established stable cervical cancer cell lines with CD38 over-expressed...
May 23, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28543796/mxd1-mediates-hypoxia-induced-cisplatin-resistance-in-osteosarcoma-cells-by-repression-of-the-pten-tumor-suppressor-gene
#19
Datong Zheng, Weiling Wu, Na Dong, Xiuqin Jiang, Jinjin Xu, Xi Zhan, Zhengdong Zhang, Zhenzhen Hu
Hypoxia-induced chemoresistance remains a major obstacle to treating osteosarcoma effectively. Mxd1, a member of the Myc/Max/Mxd family, was shown to be involved in the development of drug resistance under hypoxia. However, the effect of Mxd1 on hypoxia-induced cisplatin (CDDP) resistance and its mechanism in osteosarcoma have not been fully elucidated. In this study, we demonstrated that HIF-1α-induced Mxd1 contributed to CDDP resistance in hypoxic U-2OS and MG-63 cells. The knockdown of Mxd1 expression elevated PTEN expression at both protein and RNA levels in these hypoxic cells...
May 23, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28543759/abrus-agglutinin-promotes-irreparable-dna-damage-by-triggering-ros-generation-followed-by-atm-p73-mediated-apoptosis-in-oral-squamous-cell-carcinoma
#20
Niharika Sinha, Prashanta Kumar Panda, Prajna Paramita Naik, Durgesh Nandini Das, Subhadip Mukhopadhyay, Tapas K Maiti, Muthu K Shanmugam, Arunachalam Chinnathambi, M E Zayed, Sulaiman Ali Alharbi, Gautam Sethi, Rajesh Agarwal, Sujit K Bhutia
Oral cancer, a type of head and neck cancer, is ranked as one of the top most malignancies in India. Herein, we evaluated the anticancer efficacy of Abrus agglutinin (AGG), a plant lectin, in oral squamous cell carcinoma. AGG selectively inhibited cell growth, and caused cell cycle arrest and mitochondrial apoptosis through a reactive oxygen species (ROS)-mediated ATM-p73 dependent pathway in FaDu cells. AGG-induced ROS accumulation was identified as the major mechanism regulating apoptosis, DNA damage and DNA-damage response, which were significantly reversed by ROS scavenger N-acetylcysteine (NAC)...
May 23, 2017: Molecular Carcinogenesis
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