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Genes & Cancer

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https://www.readbyqxmd.com/read/28050233/signaling-transcript-profile-of-the-asexual-intraerythrocytic-development-cycle-of-plasmodium-falciparum-induced-by-melatonin-and-camp
#1
Wânia Rezende Lima, Giulliana Tessarin-Almeida, Andrei Rozanski, Kleber S Parreira, Miriam S Moraes, David C Martins, Ronaldo F Hashimoto, Pedro A F Galante, Célia R S Garcia
According to the World Health Organization (WHO), Plasmodium falciparum is the deadliest parasite among all species. This parasite possesses the ability to sense molecules, including melatonin (MEL) and cAMP, and modulate its cell cycle accordingly. MEL synchronizes the development of this malaria parasite by activating several cascades, including the generation of the second messenger cAMP. Therefore, we performed RNA sequencing (RNA-Seq) analysis in P. falciparum erythrocytic stages (ring, trophozoite and schizont) treated with MEL and cAMP...
September 2016: Genes & Cancer
https://www.readbyqxmd.com/read/28050232/identification-of-cetp-as-a-molecular-target-for-estrogen-positive-breast-cancer-cell-death-by-cholesterol-depleting-agents
#2
Luke Esau, Sunil Sagar, Dhinoth Bangarusamy, Mandeep Kaur
Cholesterol and its metabolites act as steroid hormone precursors, which promote estrogen receptor positive (ER+) breast cancer (BC) progression. Development of cholesterol targeting anticancer drugs has been hindered due to the lack of knowledge of viable molecular targets. Till now, Cholesteryl ester transfer protein (CETP) has been envisaged as a feasible molecular target in atherosclerosis, but for the first time, we show that CETP contributes to BC cell survival when challenged with cholesterol depleting agents...
September 2016: Genes & Cancer
https://www.readbyqxmd.com/read/28050231/treatment-of-patients-with-refractory-metastatic-cancer-according-to-molecular-profiling-on-tumor-tissue-in-the-clinical-routine-an-interim-analysis-of-the-onco-t-profile-project
#3
Andreas Seeber, Guenther Gastl, Christian Ensinger, Gilbert Spizzo, Wolfgang Willenbacher, Florian Kocher, Christoph Leitner, Ella Willenbacher, Arno Amann, Normann Steiner, Wolfgang Eisterer, Andreas Voss, Kenneth Russell, Heinz Zwierzina
INTRODUCTION: Patients with refractory metastatic cancer have been shown to benefit from molecular profiling of tumor tissue. The ONCO-T-PROFILE project was launched in March 2014 at the Innsbruck Medical University. Within 2 years our project aims to recruit 110 patients with stage IV cancer refractory to standard therapy. Our data presented here are based on an interim-analysis. METHODS: Tumor tissue specimens were submitted for molecular profiling to the certified laboratory (Caris Life Science, USA)...
September 2016: Genes & Cancer
https://www.readbyqxmd.com/read/28050230/givinostat-a-type-ii-histone-deacetylase-inhibitor-induces-potent-caspase-dependent-apoptosis-in-human-lymphoblastic-leukemia
#4
Ying Li, Kevin Zhao, Chenjiao Yao, Samir Kahwash, Yan Tang, Guojiuan Zhang, Kara Patterson, Qi-En Wang, Weiqiang Zhao
Unlike chronic myeloid leukemia, patients with acute lymphoblastic leukemia (ALL) with Philadelphia chromosome (Ph+) do not respond well to Imatinib or tyrosine kinase inhibitors (TKI). In addition, TKI might induce resistant mutations in kinase domain (KD) of ABL in patients with relapsed diseases. Of the histone deacetylase (HDAC) inhibitors, suberoylanilide hydroxamic acid (SAHA) has shown to induce potent cytotoxicity on acute myeloid leukemia cell lines but Givinostat effect on acute lymphoblastic leukemia (ALL) has not been reported...
September 2016: Genes & Cancer
https://www.readbyqxmd.com/read/28050229/dual-function-of-mdm2-and-mdmx-toward-the-tumor-suppressors-p53-and-rb
#5
REVIEW
Jesús Hernández-Monge, Adriana Berenice Rousset-Roman, Ixaura Medina-Medina, Vanesa Olivares-Illana
The orchestrated crosstalk between the retinoblastoma (RB) and p53 pathways contributes to preserving proper homeostasis within the cell. The deregulation of one or both pathways is a common factor in the development of most types of human cancer. The proto-oncoproteins MDMX and MDM2 are the main regulators of the well- known tumor suppressor p53 protein. Under normal conditions, MDM2 and MDMX inhibit p53, either via repression of its transcriptional activity by protein-protein interaction, or via polyubiquitination as a result of MDM2-E3 ubiquitin ligase activity, for which MDM2 needs to dimerize with MDMX...
September 2016: Genes & Cancer
https://www.readbyqxmd.com/read/27738496/amitriptyline-induces-mitophagy-that-precedes-apoptosis-in-human-hepg2-cells
#6
Marina Villanueva-Paz, Mario D Cordero, Ana Delgado Pavón, Beatriz Castejón Vega, David Cotán, Mario De la Mata, Manuel Oropesa-Ávila, Elizabet Alcocer-Gomez, Isabel de Lavera, Juan Garrido-Maraver, José Carrascosa, Ana Paula Zaderenko, Jordi Muntané, Manuel de Miguel, José Antonio Sánchez-Alcázar
Systemic treatments for hepatocellular carcinoma (HCC) have been largely unsuccessful. This study investigated the antitumoral activity of Amitriptyline, a tricyclic antidepressant, in hepatoma cells. Amitriptyline-induced toxicity involved early mitophagy activation that subsequently switched to apoptosis. Amitriptyline induced mitochondria dysfunction and oxidative stress in HepG2 cells. Amitriptyline specifically inhibited mitochondrial complex III activity that is associated with decreased mitochondrial membrane potential (∆Ψm) and increased reactive oxygen species (ROS) production...
July 2016: Genes & Cancer
https://www.readbyqxmd.com/read/27738495/potential-role-of-cxcl9-induced-by-endothelial-cells-cd133-liver-cancer-cells-co-culture-system-in-tumor-transendothelial-migration
#7
Qiang Ding, Yujia Xia, Shuping Ding, Panpan Lu, Liang Sun, Yuhui Fan, Xin Li, Ying Wang, De-An Tian, Mei Liu
Transendothelial migration is a pivotal step before the dissemination of tumor cells into the blood circulation. Related researches about the crosstalk between tumor cells and endothelial cells could contribute to understanding the mechanism of transendothelial migration. Cumulative studies showed that CD133 was an important marker for cancer stem cells. In our research, a co-culture system was developed to study the interaction between CD133+ liver cancer cells and human umbilical vein endothelial cells. The results showed that the direct co-cultured supernatants promoted the migration and invasion of CD133+ liver cancer cells...
July 2016: Genes & Cancer
https://www.readbyqxmd.com/read/27738494/adam17-in-tumor-associated-leukocytes-regulates-inflammatory-mediators-and-promotes-mammary-tumor-formation
#8
Laura R Bohrer, Thomas S Chaffee, Pavlina Chuntova, Nicholas J Brady, Patrice M Witschen, Sarah E Kemp, Andrew C Nelson, Bruce Walcheck, Kathryn L Schwertfeger
The presence of inflammatory cells within the tumor microenvironment has been tightly linked to mammary tumor formation and progression. Specifically, interactions between tumor cells and infiltrating macrophages can contribute to the generation of a pro-tumorigenic microenvironment. Understanding the complex mechanisms that drive tumor cell-macrophage cross-talk will ultimately lead to the development of approaches to prevent or treat early stage breast cancers. As described here, we demonstrate that the cell surface protease a disintegrin and metalloproteinase 17 (ADAM17) is expressed by macrophages in mammary tumors and contributes to regulating the expression of pro-inflammatory mediators, including inflammatory cytokines and the inflammatory mediator cyclooxygenase-2 (Cox-2)...
July 2016: Genes & Cancer
https://www.readbyqxmd.com/read/27738493/pathway-analysis-of-bladder-cancer-genome-wide-association-study-identifies-novel-pathways-involved-in-bladder-cancer-development
#9
Meng Chen, Nathaniel Rothman, Yuanqing Ye, Jian Gu, Paul A Scheet, Maosheng Huang, David W Chang, Colin P Dinney, Debra T Silverman, Jonine D Figueroa, Stephen J Chanock, Xifeng Wu
Genome-wide association studies (GWAS) are designed to identify individual regions associated with cancer risk, but only explain a small fraction of the inherited variability. Alternative approach analyzing genetic variants within biological pathways has been proposed to discover networks of susceptibility genes with additional effects. The gene set enrichment analysis (GSEA) may complement and expand traditional GWAS analysis to identify novel genes and pathways associated with bladder cancer risk. We selected three GSEA methods: Gen-Gen, Aligator, and the SNP Ratio Test to evaluate cellular signaling pathways involved in bladder cancer susceptibility in a Texas GWAS population...
July 2016: Genes & Cancer
https://www.readbyqxmd.com/read/27738492/narrowing-the-focus-a-toolkit-to-systematically-connect-oncogenic-signaling-pathways-with-cancer-phenotypes
#10
Katherine R Singleton, Kris C Wood
Functional genomics approaches such as gain- and loss-of-function screening can efficiently reveal genes that control cancer cell growth, survival, signal transduction, and drug resistance, but distilling the results of large-scale screens into actionable therapeutic strategies is challenging given our incomplete understanding of the functions of many genes. Research over several decades, including the results of large-scale cancer sequencing projects, has made it clear that many oncogenic properties are controlled by a common set of core oncogenic signaling pathways...
July 2016: Genes & Cancer
https://www.readbyqxmd.com/read/27551335/melatonin-decreases-estrogen-receptor-binding-to-estrogen-response-elements-sites-on-the-oct4-gene-in-human-breast-cancer-stem-cells
#11
Juliana Lopes, David Arnosti, James E Trosko, Mei-Hui Tai, Debora Zuccari
Cancer stem cells (CSCs) pose a challenge in cancer treatment, as these cells can drive tumor growth and are resistant to chemotherapy. Melatonin exerts its oncostatic effects through the estrogen receptor (ER) pathway in cancer cells, however its action in CSCs is unclear. Here, we evaluated the effect of melatonin on the regulation of the transcription factor OCT4 (Octamer Binding 4) by estrogen receptor alpha (ERα) in breast cancer stem cells (BCSCs). The cells were grown as a cell suspension or as anchorage independent growth, for the mammospheres growth, representing the CSCs population and treated with 10 nM estrogen (E2) or 10 μM of the environmental estrogen Bisphenol A (BPA) and 1 mM of melatonin...
May 2016: Genes & Cancer
https://www.readbyqxmd.com/read/27551334/combination-of-jak2-and-hsp90-inhibitors-an-effective-therapeutic-option-in-drug-resistant-chronic-myelogenous-leukemia
#12
Sandip N Chakraborty, Xiaohong Leng, Bastianella Perazzona, Xiaoping Sun, Yu-Hsi Lin, Ralph B Arlinghaus
Recent studies suggest that JAK2 serves as a novel therapeutic target in Bcr-Abl+ chronic myelogenous leukemia (CML). We have reported the existence of an HSP90- associated high molecular weight network complex (HMWNC) that is composed of HSP90 client proteins BCR-ABL, JAK2, and STAT3 in wild type Bcr-Abl+ leukemic cells. Here we showed that the HSP90-HMWNC is present in leukemia cells from CML patients in blast stage, and in Imatinib (IM)-resistant 32Dp210 (T315I) leukemia cells. We found that the HSP90-HMWNC could be disassembled by depleting JAK2 with either Jak2-specific shRNA or treatment with JAK2 inhibitors (TG101209 or Ruxolitinib) and HSP90 inhibitor (AUY922)...
May 2016: Genes & Cancer
https://www.readbyqxmd.com/read/27551333/genetic-determinants-in-head-and-neck-squamous-cell-carcinoma-and-their-influence-on-global-personalized-medicine
#13
Nicole L Michmerhuizen, Andrew C Birkeland, Carol R Bradford, J Chad Brenner
While sequencing studies have provided an improved understanding of the genetic landscape of head and neck squamous cell carcinomas (HNSCC), there remains a significant lack of genetic data derived from non-Caucasian cohorts. Additionally, there is wide variation in HNSCC incidence and mortality worldwide both between and within various geographic regions. These epidemiologic differences are in part accounted for by varying exposure to environmental risk factors such as tobacco, alcohol, high risk human papilloma viruses and betel quid...
May 2016: Genes & Cancer
https://www.readbyqxmd.com/read/27551332/short-form-ron-is-a-novel-determinant-of-ovarian-cancer-initiation-and-progression
#14
Katherine M Moxley, Luyao Wang, Alana L Welm, Magdalena Bieniasz
Short-form Ron (sfRon) is an understudied, alternative isoform of the full-length Ron receptor tyrosine kinase. In contrast to Ron, which has been shown to be an important player in many cancers, little is known about the role of sfRon in cancer pathogenesis. Here we report the striking discovery that sfRon expression is required for development of carcinogen-induced malignant ovarian tumors in mice. We also show that sfRon is expressed in several subtypes of human ovarian cancer including high-grade serous carcinomas, which is in contrast to no detectable expression in healthy ovaries...
May 2016: Genes & Cancer
https://www.readbyqxmd.com/read/27551331/muc4-is-negatively-regulated-through-the-wnt-%C3%AE-catenin-pathway-via-the-notch-effector-hath1-in-colorectal-cancer
#15
Priya Pai, Satyanarayana Rachagani, Punita Dhawan, Yuri M Sheinin, Muzafar A Macha, Asif Khurshid Qazi, Seema Chugh, Moorthy P Ponnusamy, Kavita Mallya, Ramesh Pothuraju, Surinder K Batra
MUC4 is a transmembrane mucin lining the normal colonic epithelium. The aberrant/de novo over-expression of MUC4 is well documented in malignancies of the pancreas, ovary and breast. However, studies have reported the loss of MUC4 expression in the majority of colorectal cancers (CRCs). A MUC4 promoter analysis showed the presence of three putative TCF/LEF sites, implying a possible regulation by the Wnt/β-catenin pathway, which has been shown to drive CRC progression. Thus, the objective of our study was to determine whether MUC4 is regulated by β-catenin in CRC...
May 2016: Genes & Cancer
https://www.readbyqxmd.com/read/27551330/a-chemoproteomic-method-for-identifying-cellular-targets-of-covalent-kinase-inhibitors
#16
Ying-Chu Chen, Chao Zhang
Protein kinases are attractive drug targets for numerous human diseases including cancers, diabetes and neurodegeneration. A number of kinase inhibitors that covalently target a cysteine residue in their target kinases have recently entered use in the cancer clinic. Despite the advantages of covalent kinases inhibitors, their inherent reactivity can lead to non-specific binding to other cellular proteins and cause off- target effects in cells. It is thus essential to determine the identity of these off targets in order to fully account for the phenotype and to improve the selectivity and efficacy of covalent inhibitors...
May 2016: Genes & Cancer
https://www.readbyqxmd.com/read/27382437/epigenetically-silenced-gng4-inhibits-sdf1%C3%AE-cxcr4-signaling-in-mesenchymal-glioblastoma
#17
Jagriti Pal, Vikas Patil, Baisakhi Mondal, Sudhanshu Shukla, Alangar S Hegde, Arimappamagan Arivazhagan, Vani Santosh, Kumaravel Somasundaram
The most common and aggressive form of primary brain tumor in adults is glioblastoma (GBM). From the global DNA methylation profiling study, previously published from our laboratory, we identified Guanine Nucleotide binding-protein Gamma subunit 4 (GNG4) to be one of the most hyper methylated and down regulated genes in GBM. GBM derived cell lines showed reduced GNG4 transcript levels, which could be reversed by methylation inhibitor treatment. Bisulphite sequencing confirmed the methylation status in glioblastoma tumor tissue and GBM derived cell lines...
March 2016: Genes & Cancer
https://www.readbyqxmd.com/read/27382436/fgf19-functions-as-autocrine-growth-factor-for-hepatoblastoma
#18
David J Elzi, Meihua Song, Barron Blackman, Susan T Weintraub, Dolores López-Terrada, Yidong Chen, Gail E Tomlinson, Yuzuru Shiio
Hepatoblastoma is the most common liver cancer in children, accounting for over 65% of all childhood liver malignancies. Hepatoblastoma is distinct from adult liver cancer in that it is not associated with hepatitis virus infection, cirrhosis, or other underlying liver pathology. The paucity of appropriate cell and animal models has been hampering the mechanistic understanding of hepatoblastoma pathogenesis. Consequently, there is no molecularly targeted therapy for hepatoblastoma. To gain insight into cytokine signaling in hepatoblastoma, we employed mass spectrometry to analyze the proteins secreted from Hep293TT hepatoblastoma cell line we established and identified the specific secretion of fibroblast growth factor 19 (FGF19), a growth factor for liver cells...
March 2016: Genes & Cancer
https://www.readbyqxmd.com/read/27382435/muc16-contributes-to-the-metastasis-of-pancreatic-ductal-adenocarcinoma-through-focal-adhesion-mediated-signaling-mechanism
#19
Sakthivel Muniyan, Dhanya Haridas, Seema Chugh, Satyanarayana Rachagani, Imayavaramban Lakshmanan, Suprit Gupta, Parthasarathy Seshacharyulu, Lynette M Smith, Moorthy P Ponnusamy, Surinder K Batra
MUC16, a heavily glycosylated type-I transmembrane mucin is overexpressed in several cancers including pancreatic ductal adenocarcinoma (PDAC). Previously, we have shown that MUC16 is significantly overexpressed in human PDAC tissues. However, the functional consequences and its role in PDAC is poorly understood. Here, we show that MUC16 knockdown decreases PDAC cell proliferation, colony formation and migration in vitro. Also, MUC16 knockdown decreases the tumor formation and metastasis in orthotopic xenograft mouse model...
March 2016: Genes & Cancer
https://www.readbyqxmd.com/read/27382434/the-adenoviral-e1a-n-terminal-domain-represses-myc-transcription-in-human-cancer-cells-by-targeting-both-p300-and-trrap-and-inhibiting-myc-promoter-acetylation-of-h3k18-and-h4k16
#20
Ling-Jun Zhao, Paul M Loewenstein, Maurice Green
Human cancers frequently arise from increased expression of proto-oncogenes, such as MYC and HER2. Understanding the cellular pathways regulating the transcription and expression of proto-oncogenes is important for targeted therapies for cancer treatment. Adenoviral (Ad) E1A 243R (243 aa residues) is a viral oncoprotein that interacts with key regulators of gene transcription and cell proliferation. We have shown previously that the 80 amino acid N-terminal transcriptional repression domain of E1A 243R (E1A 1-80) can target the histone acetyltransferase (HAT) p300 and repress HER2 in the HER2-overexpressing human breast cancer cell line SKBR3...
March 2016: Genes & Cancer
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