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Genes & Cancer

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https://www.readbyqxmd.com/read/28435520/genetically-transforming-human-osteoblasts-to-sarcoma-development-of-an-osteosarcoma-model
#1
Yi Yang, Rui Yang, Michael Roth, Sajida Piperdi, Wendong Zhang, Howard Dorfman, Pulivarthi Rao, Amy Park, Sandeep Tripathi, Carrie Freeman, Yunjia Zhang, Rebecca Sowers, Jeremy Rosenblum, David Geller, Bang Hoang, Jonathan Gill, Richard Gorlick
Osteosarcoma is the most common primary malignant bone tumor in children and young adults. Although histologically defined by the presence of malignant osteoid, the tumor possesses lineage multipotency suggesting it could be derived from a cell anywhere on the differentiation pathway between a mesenchymal stem cell (MSC) and a mature osteoblast. To determine if preosteoblasts (pOB) could be the cell of origin differentiated MSCs were transformed with defined genetic elements. MSCs and pOB differentiated from the same MSCs were serially transformed with the oncogenes hTERT, SV40 large T antigen and H-Ras...
January 2017: Genes & Cancer
https://www.readbyqxmd.com/read/28435519/gt198-psmc3ip-germline-variants-in-early-onset-breast-cancer-patients-from-hereditary-breast-and-ovarian-cancer-families
#2
Stephanie Schubert, Tim Ripperger, Melanie Rood, Anthony Petkidis, Winfried Hofmann, Hildegard Frye-Boukhriss, Marcel Tauscher, Bernd Auber, Ursula Hille-Betz, Thomas Illig, Brigitte Schlegelberger, Doris Steinemann
GT198, located 470 kb downstream of BRCA1, encodes for the nuclear PSMC3-interacting protein, which functions as co-activator of steroid hormone-mediated gene expression, and is involved in RAD51 and DMC1-mediated homologous recombination during DNA repair of double-strand breaks. Recently, germline variants in GT198 have been identified in hereditary breast and ovarian cancer (HBOC) patients, mainly in cases with early-onset. We screened a cohort of 166 BRCA1/2 mutation-negative HBOC patients, of which 56 developed early-onset breast cancer before the age of 36 years, for GT198 variants...
January 2017: Genes & Cancer
https://www.readbyqxmd.com/read/28435518/sparc-overexpression-alters-microrna-expression-profiles-involved-in-tumor-progression
#3
Bhavesh K Ahir, Nasya M Elias, Sajani S Lakka
Medulloblastoma is the most common malignant brain tumor in children. SPARC (secreted protein acidic and rich in cysteine), a multicellular non-structural glycoprotein is known to be involved in multiple processes in various cancers. Previously, we reported that SPARC expression significantly impairs medulloblastoma tumor growth in vitro and in vivo and also alters chemo sensitivity. MicroRNAs are a class of post-transcriptional gene regulators with critical functions in tumor progression. In addition, microRNA (miRNA) expression changes are also involved in chemo-resistance...
January 2017: Genes & Cancer
https://www.readbyqxmd.com/read/28435517/inhibition-of-the-platelet-derived-growth-factor-receptor-beta-pdgfrb-using-gene-silencing-crenolanib-besylate-or-imatinib-mesylate-hampers-the-malignant-phenotype-of-mesothelioma-cell-lines
#4
Ombretta Melaiu, Calogerina Catalano, Chiara De Santi, Monica Cipollini, Gisella Figlioli, Lucia Pellè, Elisa Barone, Monica Evangelista, Alice Guazzelli, Laura Boldrini, Elisa Sensi, Alessandra Bonotti, Rudy Foddis, Alfonso Cristaudo, Luciano Mutti, Gabriella Fontanini, Federica Gemignani, Stefano Landi
Malignant pleural mesothelioma (MPM) is a cancer of the pleural cavity resistant to chemotherapy. The identification of novel therapeutic targets is needed to improve its poor prognosis. Following a review of literature and a screening of specimens we found that platelet-derived growth factor receptor beta (PDGFRB) is over-expressed, but not somatically mutated, in MPM tissues. We aimed to ascertain whether PDGFRB is a MPM-cancer driver gene. The approaches employed included the use of gene silencing and the administration of small molecules, such as crenolanib and imatinib (PDGFR inhibitors) on MPM cell lines (IstMes2, Mero-14, Mero-25)...
January 2017: Genes & Cancer
https://www.readbyqxmd.com/read/28435516/docosahexaenoic-acid-dha-promotes-immunogenic-apoptosis-in-human-multiple-myeloma-cells-induces-autophagy-and-inhibits-stat3-in-both-tumor-and-dendritic-cells
#5
Donatella D'Eliseo, Livia Di Renzo, Angela Santoni, Francesca Velotti
Docosahexaenoic acid (DHA), a ω-3 polyunsaturated fatty acid found in fish oil, is a multi-target agent and exerts anti-inflammatory and anticancer activities alone or in combination with chemotherapies. Combinatorial anticancer therapies, which induce immunogenic apoptosis, autophagy and STAT3 inhibition have been proposed for long-term therapeutic success. Here, we found that DHA promoted immunogenic apoptosis in multiple myeloma (MM) cells, with no toxicity on PBMCs and DCs. Immunogenic apoptosis was shown by the emission of specific DAMPs (CRT, HSP90, HMGB1) by apoptotic MM cells and the activation of their pro-apoptotic autophagy...
January 2017: Genes & Cancer
https://www.readbyqxmd.com/read/28191286/the-regulation-of-tumor-suppressor-protein-p53-and-estrogen-receptor-er%C3%AE-by-resveratrol-in-breast-cancer-cells
#6
Julieta Saluzzo, Kelly M Hallman, Katie Aleck, Brigitte Dwyer, Meghan Quigley, Viktoria Mladenovik, Amy E Siebert, Sumi Dinda
Resveratrol (RES) is a natural antioxidant found abundantly in grapes, peanuts, and berries, and is known to possess anti-tumorigenic properties. However, there is a noticeable lack of studies on the mechanistic effects of Resveratrol on tumor suppressors. Previous studies from our laboratory have shown the tumor suppressor protein p53 and estrogen receptor-alpha (ERα) to be possible molecular targets for RES. In this study, the anti-estrogenic effects of RES were analyzed on the expression of ERα and p53...
November 2016: Genes & Cancer
https://www.readbyqxmd.com/read/28191285/autoantibodies-against-oncogenic-erg-protein-in-prostate-cancer-potential-use-in-diagnosis-and-prognosis-in-a-panel-with-c-myc-amacr-and-herv-k-gag
#7
Anshu Rastogi, Amina Ali, Shyh-Han Tan, Sreedatta Banerjee, Yongmei Chen, Jennifer Cullen, Charles P Xavier, Ahmed A Mohamed, Lakshmi Ravindranath, Jigisha Srivastav, Denise Young, Isabell A Sesterhenn, Jacob Kagan, Sudhir Srivastava, David G McLeod, Inger L Rosner, Gyorgy Petrovics, Albert Dobi, Shiv Srivastava, Alagarsamy Srinivasan
Overdiagnosis and overtreatment of prostate cancer (CaP) is attributable to widespread reliance on PSA screening in the US. This has prompted us and others to search for improved biomarkers for CaP, to facilitate early detection and disease stratification. In this regard, autoantibodies (AAbs) against tumor antigens could serve as potential candidates for diagnosis and prognosis of CaP. Towards this, our goals were: i) To investigate whether AAbs against ERG oncoprotein (overexpressed in 25-50% of Caucasian American and African American CaP) are present in the sera of CaP patients; ii) To evaluate an AAb panel to enhance CaP detection...
November 2016: Genes & Cancer
https://www.readbyqxmd.com/read/28191284/e3-ubiquitin-ligase-pirh2-enhances-tumorigenic-properties-of-human-non-small-cell-lung-carcinoma-cells
#8
Alexandra Daks, Alexey Petukhov, Olga Fedorova, Oleg Shuvalov, Valeriy Merkulov, Elena Vasileva, Alexey Antonov, Nikolai A Barlev
The product of RCHY1 human gene, Pirh2, is a RING-finger containing E3 ligase that modifies p53 with ubiquitin residues resulting in its subsequent degradation in proteasomes. Transcription of RCHY1 is regulated by p53 itself thus forming a negative regulatory feedback loop. Functionally, by eliminating p53, Pirh2 facilitates tumorigenesis. However, the role of Pirh2 in cancer cells lacking p53 is yet not well understood. Therefore, we decided to elucidate the role of Pirh2 in p53-negative human non-small cell lung carcinoma cells, H1299...
November 2016: Genes & Cancer
https://www.readbyqxmd.com/read/28191283/active-%C3%AE-catenin-is-regulated-by-the-pten-pi3-kinase-pathway-a-role-for-protein-phosphatase-pp2a
#9
Amit Persad, Geetha Venkateswaran, Li Hao, Maria E Garcia, Jenny Yoon, Jaskiran Sidhu, Sujata Persad
Dysregulation of Wnt/β-catenin signaling has been associated with the development and progression of many cancers. The stability and subcellular localization of β-catenin, a dual functional protein that plays a role in intracellular adhesion and in regulating gene expression, is tightly regulated. However, little is known about the transcriptionally active form of β-catenin, Active Beta Catenin (ABC), that is unphosphorylated at serine 37 (Ser37) and threonine 41 (Thr41). Elucidating the mechanism by which β-catenin is activated to generate ABC is vital to the development of therapeutic strategies to block β-catenin signaling for cancer treatment...
November 2016: Genes & Cancer
https://www.readbyqxmd.com/read/28191282/the-liquid-biopsy-in-lung-cancer
#10
REVIEW
Junaid Ansari, Jungmi W Yun, Anvesh R Kompelli, Youmna E Moufarrej, Jonathan S Alexander, Guillermo A Herrera, Rodney E Shackelford
The incidence of lung cancer has significantly increased over the last century, largely due to smoking, and remains the most common cause of cancer deaths worldwide. This is often due to lung cancer first presenting at late stages and a lack of curative therapeutic options at these later stages. Delayed diagnoses, inadequate tumor sampling, and lung cancer misdiagnoses are also not uncommon due to the limitations of the tissue biopsy. Our better understanding of the tumor microenvironment and the systemic actions of tumors, combined with the recent advent of the liquid biopsy, may allow molecular diagnostics to be done on circulating tumor markers, particularly circulating tumor DNA...
November 2016: Genes & Cancer
https://www.readbyqxmd.com/read/28191281/switching-off-malignant-mesothelioma-exploiting-the-hypoxic-microenvironment
#11
REVIEW
Noushin Nabavi, Kevin L Bennewith, Andrew Churg, Yuzhuo Wang, Colin C Collins, Luciano Mutti
Malignant mesotheliomas are aggressive, asbestos-related cancers with poor patient prognosis, typically arising in the mesothelial surfaces of tissues in pleural and peritoneal cavity. The relative unspecific symptoms of mesotheliomas, misdiagnoses, and lack of precise targeted therapies call for a more critical assessment of this disease. In the present review, we categorize commonly identified genomic aberrations of mesotheliomas into their canonical pathways and discuss targeting these pathways in the context of tumor hypoxia, a hallmark of cancer known to render solid tumors more resistant to radiation and most chemo-therapy...
November 2016: Genes & Cancer
https://www.readbyqxmd.com/read/28050233/signaling-transcript-profile-of-the-asexual-intraerythrocytic-development-cycle-of-plasmodium-falciparum-induced-by-melatonin-and-camp
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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