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Molecular Carcinogenesis

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https://www.readbyqxmd.com/read/28224663/loss-of-mlh1-sensitizes-colon-cancer-cells-to-dna-pkcs-inhibitor-ku60648
#1
Inga Hinrichsen, Anne Ackermann, Tonja Düding, Annika Graband, Natalie Filmann, Guido Plotz, Stefan Zeuzem, Angela Brieger
Germline mutations of MLH1 are responsible for tumor generation in nearly 50% of patients with Lynch Syndrome, and around 15% of sporadic colorectal cancers show MLH1-deficiency due to promotor hypermethylation. Although these tumors are of lower aggressiveness the benefit for these patients from standard chemotherapy is still under discussion. Recently, it was shown that the sensitivity to the DNA-PKcs inhibitor KU60648 is linked to loss of the MMR protein MSH3. However, loss of MSH3 is rather secondary, as a consequence of MMR-deficiency, and frequently detectable in MLH1-deficient tumors...
February 22, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28218476/overexpression-of-tet-dioxygenases-in-seminomas-associates-with-low-levels-of-dna-methylation-and-hydroxymethylation
#2
Martina Benešová, Kateřina Trejbalová, Dana Kučerová, Zdenka Vernerová, Tomáš Hron, Arpád Szabó, Rachel Amouroux, Petr Klézl, Petra Hajkova, Jiří Hejnar
Germ cell tumors and particularly seminomas reflect the epigenomic features of their parental primordial germ cells, including genomic DNA hypomethylation and expression of pluripotent cell markers. Because the DNA hypomethylation might be a result of TET dioxygenase activity, we examined expression of TET1-3 enzymes and the level of their product, 5-hydroxymethylcytosine, in a panel of histologically characterized seminomas and non-seminomatous germ cell tumors. Expression of TET dioxygenase mRNAs was quantified by real-time PCR...
February 20, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28218475/profound-changes-in-mirna-expression-during-cancer-initiation-by-aflatoxin-b1-and-their-abrogation-by-the-chemopreventive-triterpenoid-cddo-im
#3
Merricka C Livingstone, Natalie M Johnson, Bill D Roebuck, Thomas W Kensler, John D Groopman
Aflatoxin B1 (AFB1 ) is a potent human and animal hepatocarcinogen. To investigate the effects of aflatoxin on miRNA expression during the initiation phase of carcinogenesis, next-generation sequencing was used to analyze liver tissues from F344 rats exposed to 200 µg/kg per day AFB1 for 4 weeks. A panel of miRNAs was identified that was upregulated with AFB1 treatment compared to controls: rno-miR-434-3p, rno-miR-411-5p, rno-miR-221-3p, rno-miR-127-3p, rno-miR-205, rno-miR-429, rno-miR-34a-5p, rno-miR-181c-3p, rno-miR-200b-3p, and rno-miR-541-5p...
February 20, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28218473/epigenetic-silencing-of-diacylglycerol-kinase-gamma-in-colorectal-cancer
#4
Masahiro Kai, Eiichiro Yamamoto, Akiko Sato, Hiro-O Yamano, Takeshi Niinuma, Hiroshi Kitajima, Taku Harada, Hironori Aoki, Reo Maruyama, Mutsumi Toyota, Tomo Hatahira, Hiroshi Nakase, Tamotsu Sugai, Toshiharu Yamashita, Minoru Toyota, Hiromu Suzuki
Diacylglycerol kinases (DGKs) are important regulators of cell signaling and have been implicated in human malignancies. Whether epigenetic alterations are involved in the dysregulation of DGKs in cancer is unknown, however. We therefore analyzed methylation of the promoter CpG islands of DGK genes in colorectal cancer (CRC) cell lines. We found that DGKG, which encodes DGKγ, was hypermethylated in all CRC cell lines tested (n = 9), but was not methylated in normal colonic tissue. Correspondingly, DGKG expression was suppressed in CRC cell lines but not in normal colonic tissue, and was restored in CRC cells by treatment with the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine (5-aza-dC)...
February 20, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28218467/divergent-roles-of-p120-catenin-isoforms-linked-to-altered-cell-viability-proliferation-and-invasiveness-in-carcinogen-induced-rat-skin-tumors
#5
Rong Wang, Ying-Shiuan Chen, Wan-Mohaiza Dashwood, Qingjie Li, Christiane V Löhr, Kay Fischer, Emily Ho, David E Williams, Roderick H Dashwood
The heterocyclic amine 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) targets multiple organs for tumorigenesis in the rat, including the colon and the skin. PhIP-induced skin tumors were subjected to mutation screening, which identified genetic changes in Hras (7/40, 17.5%) and Tp53 (2/40, 5%), but not in Ctnnb1, a commonly mutated gene in PhIP-induced colon tumors. Despite the absence of Ctnnb1 mutations, β-catenin was overexpressed in nuclear and plasma membrane fractions from PhIP-induced skin tumors, coinciding with loss of p120-catenin from the plasma membrane, and the appearance of multiple p120-catenin-associated bands in the nuclear extracts...
February 20, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28218464/curcumin-analogue-l48h37-induces-apoptosis-through-ros-mediated-endoplasmic-reticulum-stress-and-stat3-pathways-in-human-lung-cancer-cells
#6
Chen Feng, Yiqun Xia, Peng Zou, Miaoshan Shen, Jie Hu, Shilong Ying, Jialing Pan, Zhiguo Liu, Xuanxuan Dai, Weishan Zhuge, Guang Liang, Yeping Ruan
Lung cancer is the leading cause of cancer-related deaths. Curcumin is a well-known natural product with anticancer ability, however, its poor bioavailability and pharmacokinetic profiles have limited its application in anticancer therapy. Previously we reported that L48H37, a novel analogue of curcumin with higher bioavailability, ameliorated LPS-induced inflammation, but the anticancer effect of L48H37 is still unknown. In the present study, we have investigated the effects of L48H37 in human lung cancer cells...
February 20, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28218462/tungsten-exposure-causes-a-selective-loss-of-histone-demethylase-protein
#7
Freda Laulicht Glick, Feng Wu, Xiaoru Zhang, Ashley Jordan, Jason Brocato, Thomas Kluz, Hong Sun, Max Costa
In the course of our investigations into the toxicity of tungstate, we discovered that cellular exposure resulted in the loss of the histone demethylase protein. We specifically investigated the loss of two histone demethylase dioxygenases, JARID1A and JMJD1A. Both of these proteins were degraded in the presence of tungstate and this resulted in increased global levels of H3K4me3 and H3K9me2, the substrates of JARID1A and JMJD1A respectively. Treatment with MG132 completely inhibited the loss of the demethylase proteins induced by tungstate treatment, suggesting that tungstate activated the proteasomal degradation of these proteins...
February 20, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28218450/chromium-iv-exposure-via-src-ras-signaling-promotes-cell-transformation
#8
Suthakar Ganapathy, Ping Li, Jean Lafontant, Rui Xiong, Tianqi Yu, Guojun Zhang, Changyan Chen
Hexavalent chromium [Cr(VI)] is a well-known environment carcinogen. The exposure of Cr(VI) through contaminated soil, air particles and drinking water is a strong concern for the public health worldwide. While many studies have been done, it remains unclear which intracellular molecules transduce Cr(VI)-mediated carcinogenic signaling in cells to promote cancer. In this study, we demonstrated that upon Cr(VI) treatment, the intracellular receptor src was activated, which further upregulated Ras activity, leading to the augmentation of ROS and onset of ER stress in human lung epithelial BEAS-2B or keratinocytes...
February 20, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28218435/a-low-frequency-variant-in-smad7-modulates-tgf-%C3%AE-signaling-and-confers-risk-for-colorectal-cancer-in-chinese-population
#9
Jiaoyuan Li, Li Zou, Ying Zhou, Lu Li, Ying Zhu, Yang Yang, Yajie Gong, Jiao Lou, Juntao Ke, Yi Zhang, Jianbo Tian, Danyi Zou, Xiating Peng, Jiang Chang, Jing Gong, Rong Zhong, Xiaobo Zhou, Xiaoping Miao
The TGF-β pathway plays an essential role in regulating cell proliferation and differentiation. GWASs and candidate approaches have identified a battery of genetic variants in the TGF-β pathway contributing to colorectal cancer (CRC). However, most of the significant variants are common variants and their functions remain ambiguous. To identify causal variants with low-frequency in the TGF-β pathway contributing to CRC susceptibility in Chinese population, we performed targeted sequencing of 12 key genes in TGF-β signaling in CRC patients followed by a two-stage case-control study with a total of 5109 cases and 5169 controls...
February 20, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28218426/dkk3-attenuates-the-cytotoxic-effect-of-natural-killer-cells-on-cd133-gastric-cancer-cells
#10
Pu Xia, Xiao-Yan Xu
Cancer stem cell (CSCs) has started a new era in cancer research. CD133 is a widely used marker for identification of CSCs. More and more studies showed that NK cells preferentially target cancer stem-like cells. However, the deeper mechanism of the susceptibility of cancer stem cells to NK cells remains unclear. In this study, we isolated CD133 positive population of a gastric cancer cell line, BGC823 cells, and cultured with NK cells. We found that CD133 could efficiently active NK cells in an NKG2D-dependent manner...
February 20, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28218425/the-role-of-lipid-raft-translocation-of-prohibitin-in-regulation-of-akt-and-raf-protected-apoptosis-of-hacat-cells-upon-ultraviolet-b-irradiation
#11
Qiong Wu, Shiyong Wu
Prohibitin (PHB) plays a role in regulation of ultraviolet B light (UVB)-induced apoptosis of human keratinocytes, HaCaT cells. The regulatory function of PHB appears to be associated with its lipid raft translocation. However, the detailed mechanism for PHB-mediated apoptosis of these keratinocytes upon UVB irradiation is not clear. In this report, we determined the role of lipid raft translocation of PHB in regulation of UVB-induced apoptosis. Our data show that upon UVB irradiation PHB is translocated from the non-raft membrane to the lipid rafts, which is correlated with a release of both Akt and Raf from membrane...
February 20, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28218424/p16-ink4a-enhances-the-transcriptional-and-the-apoptotic-functions-of-p53-through-dna-dependent-interaction
#12
Huda H Al-Khalaf, Shreeram C Nallar, Dhananjaya V Kalvakolanu, Abdelilah Aboussekhra
p16(INK4A) and p53 are two important tumor suppressor proteins that play essential roles during cell proliferation and aging through regulating the expression of several genes. Here, we report that p16(INK4A) and p53 co-regulate a plethora of transcripts. Furthermore, both proteins colocalize in the nucleus of human primary skin fibroblasts and breast luminal cells, and form a heteromer whose level increases in response to genotoxic stress as well as aging of human fibroblasts and various mouse organs. CDK4 is also present in this heteromeric complex, which is formed only in the presence of DNA both in vitro using pure recombinant proteins and in vivo...
February 20, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28218421/frameshift-mutational-target-gene-analysis-identifies-similarities-and-differences-in-constitutional-mismatch-repair-deficiency-and-lynch-syndrome
#13
Claudia Maletzki, Maja Huehns, Ingrid Bauer, Tim Ripperger, Maureen M Mork, Eduardo Vilar, Sabine Klöcking, Heike Zettl, Friedrich Prall, Michael Linnebacher
Mismatch-repair deficient (MMR-D) malignancies include Lynch Syndrome (LS), which is secondary to germline mutations in one of the MMR genes, and the rare childhood-form of constitutional mismatch repair-deficiency (CMMR-D); caused by bi-allelic MMR gene mutations. A hallmark of LS-associated cancers is microsatellite instability (MSI), characterized by coding frameshift mutations (cFSM) in target genes. By contrast, tumors arising in CMMR-D patients are thought to display a somatic mutation pattern differing from LS...
February 20, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28218420/plasma-lipoxin-a4-and-resolvin-d1-are-not-associated-with-reduced-adenoma-risk-in-a-randomized-trial-of-aspirin-to-prevent-colon-adenomas
#14
Veronika Fedirko, Gail McKeown-Eyssen, Charles N Serhan, Elizabeth L Barry, Robert S Sandler, Jane C Figueiredo, Dennis J Ahnen, Robert S Bresalier, Douglas J Robertson, Carlton W Anderson, John A Baron
Inflammation plays a major role in colon carcinogenesis. Endogenously produced specialized proresolving lipid mediators (SPMs) play a central role in inflammation and tissue homeostasis, and have been implicated in carcinogenesis. We studied the associations of plasma levels of two SPMs [lipoxin A4 (LXA4 ) and resolvin D1(RvD1)] with risk for recurrent adenoma. In this pilot study, we used data and biosamples from an adenoma chemoprevention study investigating the effects of aspirin and/or folic acid on the occurrence of colorectal adenomas...
February 20, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28150890/further-assessment-of-exome-wide-uvr-footprints-in-melanoma-and-their-possible-relevance
#15
Pamela Mukhopadhyay, James Roberts, Graeme J Walker
C > T substitutions at dipyrimidine sites dominate the melanoma genome. We recently analyzed the exomes of spontaneous and neonatal UVR-induced murine melanomas, noting a dramatic change in the genomic footprint at C > T substitutions in the latter. Here we re-analyzed published exome-wide footprints in human melanomas stratified in terms of likely previous sun exposure. Acral and mucosal melanomas were heterogeneous in terms of base substitution types, but most C > Ts occurred in the context of 3'G, probably resulting from spontaneous deamination of the cytosine...
February 2, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28150878/pathway-analysis-of-published-genome-wide-association-studies-of-lung-cancer-a-potential-role-for-the-cyp4f3-locus
#16
Jieyun Yin, Hongliang Liu, Zhensheng Liu, Kouros Owzar, Younghun Han, Li Su, Yongyue Wei, Rayjean J Hung, Yonathan Brhane, John McLaughlin, Paul Brennan, Heike Bickeboeller, Albert Rosenberger, Richard S Houlston, Neil Caporaso, Maria Teresa Landi, Joachim Heinrich, Angela Risch, David C Christiani, Christopher I Amos, Qingyi Wei
The Fatty acids (FAs) metabolism is suggested to play a pivotal role in the development of lung cancer, we explored that by conducting pathway-based analysis. We performed a meta-analysis of published datasets of six genome wide association studies (GWASs) from the Transdisciplinary Research in Cancer of the Lung (TRICL) consortium, which included 12,160 cases with lung cancer and 16,838 cancer-free controls. A total of 30,722 single-nucleotide polymorphisms (SNPs) from 317 genes relevant to FA metabolic pathways were identified...
February 2, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28150875/atp2a3-gene-as-an-important-player-for-resveratrol-anticancer-activity-in-breast-cancer-cells
#17
Eduardo Izquierdo-Torres, Gabriela Rodríguez, Iván Meneses-Morales, Angel Zarain-Herzberg
The Ca(2+) -ATPases from the Sarco/endoplasmic reticulum (SERCA) are fundamental for maintaining intracellular [Ca(2+) ] homeostasis by pumping Ca(2+) into the endoplasmic reticulum (ER) of eukaryotic cells. SERCA enzymes are encoded by three different genes (ATP2A1-3), whose expression occurs in a tissue and development stage-specific manner. It has been reported alterations in the expression of SERCA2 and SERCA3 pumps in different types of cancer: oral, lung, colon, stomach, central nervous system, thyroid, breast, and prostate...
February 2, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28150874/the-caspase-3-p120-rasgap-stress-sensing-module-reduces-liver-cancer-incidence-but-does-not-affect-overall-survival-in-gamma-irradiated-and-carcinogen-treated-mice
#18
Güliz Vanli Jaccard, Christine Sempoux, Christian Widmann
Activation of oncogenes is the initial step in cellular transformation. Oncogenes favor aberrant proliferation and this initially also induces cellular stress. This oncogenic stress can act a safeguard mechanism against further transformation by inducing senescence or apoptosis. Yet, the few premalignant cells that tolerate and escape these senescent or apoptotic responses are those that will ultimately generate tumors. The caspase-3/p120 RasGAP module is a stress-sensing device that promotes survival under mild stress conditions...
February 2, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28150872/polymorphism-in-anril-is-associated-with-relapse-in-patients-with-multiple-myeloma-after-autologous-stem-cell-transplant
#19
Ming J Poi, Junan Li, Douglas W Sborov, Zachary VanGundy, Yu Kyoung Cho, Misty Lamprecht, Flavia Pichiorri, Mitch A Phelps, Craig C Hofmeister
Multiple myeloma (MM) is a hematologic malignancy characterized by clonal proliferation of plasma cells and overproduction of monoclonal immunoglobins. Treatment with melphalan is currently standard of care for younger and fit patients when followed by hematopoietic stem cell transplantation (HSCT), and in transplant ineligible patients when used in combination regimens. It has been previously shown that changes in the p53 pathway are associated with melphalan efficacy, but the regulatory role of the p14ARF-MDM2-p53 axis has yet to be fully explored...
February 2, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28130850/demethylating-and-anti-hepatocarcinogenic-potential-of-hesperidin-a-natural-polyphenol-of-citrus-juices
#20
Zahira Fernández-Bedmar, Jaouad Anter, Angeles Alonso-Moraga, Juana Martín de Las Mulas, Yolanda Millán-Ruiz, Silvia Guil-Luna
Hepatocellular carcinoma (HCC) is a neoplasia representing the fifth most common malignancy worldwide and the third cause of death from cancer. Diets with high content in fruits and vegetables are widely recommended for their health-promoting properties, among them, the protection against diabetes, cancer and cardiovascular diseases. Hesperidin is the most important phenol in the orange fruit with well-known health benefits. Diet components have been used as possible modulator agents of DNA methylation in cancer cells and epigenetic therapy against their harmful effects could be a potential tool in chemotherapy...
January 27, 2017: Molecular Carcinogenesis
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