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https://www.readbyqxmd.com/read/29053389/mrpl53-a-new-candidate-gene-for-orofacial-clefting-identified-using-an-eqtl-approach
#1
C Masotti, L A Brito, A C Nica, K U Ludwig, K Nunes, C P Savastano, C Malcher, S G Ferreira, G S Kobayashi, D F Bueno, N Alonso, D Franco, A Rojas-Martinez, S E Dos Santos, P A Galante, D Meyer, T Hünemeier, E Mangold, E T Dermitzakis, M R Passos-Bueno
A valuable approach to understand how individual and population genetic differences can predispose to disease is to assess the impact of genetic variants on cellular functions (e.g., gene expression) of cell and tissue types related to pathological states. To understand the genetic basis of nonsyndromic cleft lip with or without cleft palate (NSCL/P) susceptibility, a complex and highly prevalent congenital malformation, we searched for genetic variants with a regulatory role in a disease-related tissue, the lip muscle (orbicularis oris muscle [OOM]), of affected individuals...
October 1, 2017: Journal of Dental Research
https://www.readbyqxmd.com/read/29052525/epigenetic-mediated-zinc-finger-protein-671-downregulation-promotes-cell-proliferation-and-tumorigenicity-in-nasopharyngeal-carcinoma-by-inhibiting-cell-cycle-arrest
#2
Jian Zhang, Xin Wen, Na Liu, Ying-Qin Li, Xin-Ran Tang, Ya-Qin Wang, Qing-Mei He, Xiao-Jing Yang, Pan-Pan Zhang, Jun Ma, Ying Sun
BACKGROUND: Epigenetic abnormalities play important roles in nasopharyngeal cancer (NPC), however, the epigenetic changes associated with abnormal cell proliferation remain unclear. METHODS: We detected epigenetic change of ZNF671 in NPC tissues and cell lines by bisulfite pyrosequencing. We evaluated zinc finger protein 671 (ZNF671) expression in NPC cell lines and clinical tissues using real-time PCR and western blotting. Then, we established NPC cell lines that stably overexpressed ZNF671 and knocked down ZNF671 expression to explore its function in NPC in vitro and in vivo...
October 19, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29051161/prostate-cancer-cells-express-more-androgen-receptor-ar-following-androgen-deprivation-improving-recognition-by-ar-specific-t-cells
#3
Brian M Olson, Melissa Gamat, Joseph Seliski, Thomas Sawicki, Justin Jeffery, Leigh Ellis, Charles G Drake, Jamey Weichert, Douglas G McNeel
Androgen deprivation is the primary therapy for recurrent prostate cancer, and agents targeting the androgen receptor (AR) pathway continue to be developed. Because androgen-deprivation therapy (ADT) has immmunostimulatory effects as well as direct antitumor effects, AR-targeted therapies have been combined with other anti-cancer therapies, including immunotherapies. Here, we sought to study whether an antigen-specific mechanism of resistance to ADT (overexpression of the AR) may result in enhanced AR-specific T-cell immune recognition, and whether this might be strategically combined with an antitumor vaccine targeting the AR...
October 19, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/29050985/bromodomain-protein-brd4-promotes-cell-proliferation-in-skin-squamous-cell-carcinoma
#4
Tie Xiang, Jin-Yu Bai, Cang She, Dao-Jiang Yu, Xiao-Zhong Zhou, Tian-Lan Zhao
The present study examined the expression and biological functions of bromodomain-containing protein 4 (BRD4) in skin squamous cell carcinoma (SCC) cells. Our results show that BRD4 mRNA and protein expression was upregulated in human skin SCC cells, as compared to its level in the normal skin keratinocytes and fibroblasts. Treatment with BRD4 inhibitors, JQ1 and CPI203, resulted in proliferation inhibition, apoptosis and cell cycle arrest in both established (A431 cell line) and primary skin SCC cells. Furthermore, BRD4 knockdown (by targeted shRNAs) or knockout (by CRISPR/Cas9) largely inhibited A431 cell proliferation...
October 16, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/29050519/lncrna-pvt1-predicts-prognosis-and-regulates-tumor-growth-in-prostate-cancer
#5
Jin Yang, Cuirong Li, Ashley Mudd, Xiao Gu
Long non-coding RNA (lncRNA) plasmacytoma variant translocation 1(PVT1) was aberrantly expressed in various cancers and is associated with tumor prognosis. Here, we aim to investigate its function in prostate cancer. Small interfering RNA against PVT1 was transfected into prostate cancer cell lines and cell growth and apoptosis were analyzed. Our results showed that PVT1 was overexpressed in prostate cancer tissues and cells. Higher levels of PVT1 indicated poorer overall survival and disease-free survival...
October 20, 2017: Bioscience, Biotechnology, and Biochemistry
https://www.readbyqxmd.com/read/29050242/mir-34a-modulates-ionizing-radiation-induced-senescence-in-lung-cancer-cells
#6
Xiaoyuan He, Aimin Yang, Daniel G McDonald, Ellen C Riemer, Kenneth N Vanek, Bradley A Schulte, Gavin Y Wang
MicroRNAs (miRNAs) are a new class of gene expression regulators that have been implicated in tumorigenesis and modulation of the responses to cancer treatment including that of human non-small cell lung cancer (NSCLC). However, the role of miR-34a in ionizing radiation (IR)-induced senescence in NSCLC cells remains poorly understood. Here we report that IR-induced premature senescence correlates with upregulation of miR-34a expression in NSCLC cells. Ectopic overexpression of miR-34a by transfection with synthetic miR-34a mimics markedly enhances IR-induced senescence, whereas inhibition of miR-34a by transfection with a synthetic miR-34a inhibitor attenuates IR-induced senescence...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29050203/loss-of-egr1-a-human-del5q-gene-accelerates-bcr-abl-driven-chronic-myelogenous-leukemia
#7
Silvia Maifrede, Andrew Magimaidas, Xiaojin Sha, Kaushiki Mukherjee, Dan A Liebermann, Barbara Hoffman
There is substantial evidence that early growth response-1 (Egr1) gene, a zinc-finger transcription factor, behaves as a tumor suppressor in leukemia. This includes reports from this laboratory that constitutive Egr1 overrides leukemia conferred by deregulated c-Myc or E2F-1 in the M1 myeloid leukemic cell line by promoting differentiation. To investigate the effect of Egr1 on the initiation and progression of Chronic Myelogenous Leukemia (CML), lethally irradiated syngeneic wild type mice were reconstituted with bone marrow (BM) from either wild type or Egr1 null mice transduced with a 210-kD BCR-ABL-expressing MSCV-retrovirus (bone marrow transplantation {BMT})...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29050200/targeting-muc1-c-suppresses-polycomb-repressive-complex-1-in-multiple-myeloma
#8
Ashujit Tagde, Tahireh Markert, Hasan Rajabi, Masayuki Hiraki, Maroof Alam, Audrey Bouillez, David Avigan, Kenneth Anderson, Donald Kufe
The polycomb repressive complex 1 (PRC1) includes the BMI1, RING1 and RING2 proteins. BMI1 is required for survival of multiple myeloma (MM) cells. The MUC1-C oncoprotein is aberrantly expressed by MM cells, activates MYC and is also necessary for MM cell survival. The present studies show that targeting MUC1-C with (i) stable and inducible silencing and CRISPR/Cas9 editing and (ii) the pharmacologic inhibitor GO-203, which blocks MUC1-C function, downregulates BMI1, RING1 and RING2 expression. The results demonstrate that MUC1-C drives BMI1 transcription by a MYC-dependent mechanism...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29050113/-long-term-follow-up-of-neuroblastoma-in-children-less-than-18-months-of-age
#9
J Zhao, C Pan, M Xu, M Zhou, Y J Gao, W T Hu, J Y Tang
Objective: To assess the clinical features and long-term outcomes of neuroblastoma (NB) in children less than 18 months of age, so as to provide evidence for further improvement of treatment. Method: Clinical data(sex, age, stage, risk group, treatment response, follow-up, etc.) of 155 NB patients under age of 18 months from June 2000 to December 2015 in Shanghai Children's Medical Center were analyzed retrospectively. The clinical features were summarized and the long-term follow-up results were evaluated...
October 2, 2017: Zhonghua Er Ke za Zhi. Chinese Journal of Pediatrics
https://www.readbyqxmd.com/read/29049978/targeting-eif4e-inhibits-growth-survival-and-angiogenesis-in-retinoblastoma-and-enhances-efficacy-of-chemotherapy
#10
Genguo Wang, Zhi Li, Zhuojun Li, Yi Huang, Xiaochun Mao, Chang Xu, Sha Cui
Although the eukaryotic translation initiation factor 4E (eIF4E) has been shown to be critically involved in the transformation and progression of various tumors, little is known about the role of eIF4E in retinoblastoma. In this work, we report that ribavirin, a pharmacologic inhibitor of eIF4E function, effectively targets retinoblastoma and angiogenesis. Ribavirin treatment dose-dependently blocked the growth and stimulated apoptosis in various retinoblastoma cell lines, with IC50 values that are within the clinically achievable range...
October 16, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29049346/biological-activity-and-dimerization-state-of-modified-phytochrome-a-proteins
#11
Peng Liu, Robert A Sharrock
To assess potential physical interactions of type I phyA with the type II phyB-phyE phytochromes in vivo, transgenes expressing fusion gene forms of phyA were introduced into the Arabidopsis phyA mutant background. When a single c-Myc (myc) epitope is added to either the N- or C-terminus of phyA, the constructs completely complement phyA mutant phenotypes. However, addition of larger tags, such as six consecutive myc epitopes or the yellow fluorescent protein sequence, result in fusion proteins that show reduced activity...
2017: PloS One
https://www.readbyqxmd.com/read/29048773/use-of-a-rho-kinase-inhibitor-to-increase-human-tonsil-keratinocyte-longevity-for-three-dimensional-tissue-engineered-tonsil-epithelium-equivalents
#12
Amy K Grayson, Vanessa Hearnden, Robert Bolt, Ala Jebreel, Helen E Colley, Craig Murdoch
The generation of tissue-engineered epithelial models is often hampered by the limited proliferative capacity of primary epithelial cells. This study aimed to isolate normal tonsillar keratinocytes (NTK) from human tonsils, increase the lifespan of these cells using the Rho kinase inhibitor Y-27632 and to develop tissue-engineered equivalents of healthy and infected tonsil epithelium. The proliferation rate of isolated NTK and expression of c-MYC and p16INK4A were measured in the absence or presence of the inhibitor...
October 19, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/29048663/suppression-of-letm1-by-sirna-inhibits-cell-proliferation-and-invasion-of-bladder-cancer-cells
#13
Bisheng Huang, Jingwei Zhang, Xiaolu Zhang, Chi Huang, Guanghui Hu, Saiyang Li, Tiancheng Xie, Mengnan Liu, Yunfei Xu
The leucine zipper-EF-hand containing transmembrane protein 1 (LETM1) is highly expressed in many human malignancies and is correlated with poor prognosis. However, the function of LETM1 in bladder cancer still remains unknown. In the present study, we analyzed the expression levels of LETM1 in bladder cancer tissues and non-cancerous tissues as well as in four bladder cancer cell lines (T24, EJ, 5637 and J82) and a human bladder epithelial immortalized cell line SV-HUC-1. Small interfering RNA (siRNA) was employed to knockdown the expression of LETM1 in the T24 cells...
September 18, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29048630/metastatic-genes-targeted-by-an-antioxidant-in-an-established-radiation-%C3%A2-and-estrogen-breast-cancer-model
#14
Gloria M Calaf, Debasish Roy
Breast cancer remains the second most common disease worldwide. Radiotherapy, alone or in combination with chemotherapy, is widely used after surgery as a treatment for cancer with proven therapeutic efficacy manifested by reduced incidence of loco-regional and distant recurrences. However, clinical evidence indicates that relapses occurring after radiotherapy are associated with increased metastatic potential and poor prognosis in the breast. Among the anticarcinogenic and antiproliferative agents, curcumin is a well-known major dietary natural yellow pigment derived from the rhizome of the herb Curcuma longa (Zingiberaceae)...
September 14, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29048549/curcumin-sensitizes-pancreatic-cancer-cells-to-gemcitabine-by-attenuating-prc2-subunit-ezh2-and-the-lncrna-pvt1-expression
#15
Kazuhiro Yoshida, Shusuke Toden, Preethi Ravindranathan, Haiyong Han, Ajay Goel
Development of resistance to chemotherapeutic drugs is a major challenge in the care of patients with pancreatic ductal adenocarcinoma (PDAC). Acquired resistance to chemotherapeutic agents in PDAC has been linked to a subset of cancer cells termed 'cancer stem cells' (CSCs). Therefore, an improved understanding of the molecular events underlying the development of pancreatic CSCs is required to identify new therapeutic targets to overcome chemoresistance. Accumulating evidence indicates that curcumin, a phenolic compound extracted from turmeric, can overcome de novo chemoresistance and re-sensitize tumors to various chemotherapeutic agents...
October 1, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/29048129/realgar-nanoparticles-versus-ato-arsenic-compounds-induce-in%C3%A2-vitro-and-in%C3%A2-vivo-activity-against-multiple-myeloma
#16
Danka Cholujova, Zdenka Bujnakova, Erika Dutkova, Teru Hideshima, Richard W Groen, Constantine S Mitsiades, Paul G Richardson, David M Dorfman, Peter Balaz, Kenneth C Anderson, Jana Jakubikova
Multiple myeloma (MM), a B cell malignancy characterized by clonal proliferation of plasma cells in the bone marrow, remains incurable despite the use of novel and conventional therapies. In this study, we demonstrated MM cell cytotoxicity triggered by realgar (REA; As4 S4 ) nanoparticles (NREA) versus Arsenic trioxide (ATO) against MM cell lines and patient cells. Both NREA and ATO showed in vivo anti-MM activity, resulting in significantly decreased tumour burden. The anti-MM activity of NREA and ATO is associated with apoptosis, evidenced by DNA fragmentation, depletion of mitochondrial membrane potential, cleavage of caspases and anti-apoptotic proteins...
October 19, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/29046336/pp2a-inactivation-mediated-by-ppp2r4-haploinsufficiency-promotes-cancer-development
#17
Ward Sents, Bob Meeusen, Petar Kalev, Enrico Radaelli, Xavier Sagaert, Eline Miermans, Dorien Haesen, Caroline Lambrecht, Mieke Dewerchin, Peter Carmeliet, Jukka Westermarck, Anna Sablina, Veerle Janssens
Protein phosphatase 2A (PP2A) complexes counteract many oncogenic kinase pathways. In cancer cells, PP2A function can be compromised by several mechanisms, including sporadic mutations in its scaffolding A and regulatory B subunits or more frequently through overexpression of cellular PP2A inhibitors. Here we identify a novel genetic mechanism by which PP2A function is recurrently affected in human cancer, involving haploinsufficiency of PPP2R4, a gene encoding the cellular PP2A activator PTPA. Notably, up to 70% of cancer patients showed a heterozygous deletion or missense mutations in PPP2R4 Cancer-associated PTPA mutants exhibited decreased abilities to bind the PP2A-C subunit or activate PP2A and failed to reverse the tumorigenic phenotype induced by PTPA suppression, indicating they function as null alleles...
October 18, 2017: Cancer Research
https://www.readbyqxmd.com/read/29045844/a-b-cell-regulome-links-notch-to-downstream-oncogenic-pathways-in-small-b-cell-lymphomas
#18
Russell J H Ryan, Jelena Petrovic, Dylan M Rausch, Yeqiao Zhou, Caleb A Lareau, Michael J Kluk, Amanda L Christie, Winston Y Lee, Daniel R Tarjan, Bingqian Guo, Laura K H Donohue, Shawn M Gillespie, Valentina Nardi, Ephraim P Hochberg, Stephen C Blacklow, David M Weinstock, Robert B Faryabi, Bradley E Bernstein, Jon C Aster, Warren S Pear
Gain-of-function Notch mutations are recurrent in mature small B cell lymphomas such as mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL), but the Notch target genes that contribute to B cell oncogenesis are largely unknown. We performed integrative analysis of Notch-regulated transcripts, genomic binding of Notch transcription complexes, and genome conformation data to identify direct Notch target genes in MCL cell lines. This B cell Notch regulome is largely controlled through Notch-bound distal enhancers and includes genes involved in B cell receptor and cytokine signaling and the oncogene MYC, which sustains proliferation of Notch-dependent MCL cell lines via a Notch-regulated lineage-restricted enhancer complex...
October 17, 2017: Cell Reports
https://www.readbyqxmd.com/read/29045832/utx-kdm6a-loss-enhances-the-malignant-phenotype-of-multiple-myeloma-and-sensitizes-cells-to-ezh2-inhibition
#19
Teresa Ezponda, Daphné Dupéré-Richer, Christine M Will, Eliza C Small, Nobish Varghese, Tej Patel, Behnam Nabet, Relja Popovic, Jon Oyer, Marinka Bulic, Yupeng Zheng, Xiaoxiao Huang, Mrinal Y Shah, Sayantan Maji, Alberto Riva, Manuela Occhionorelli, Giovanni Tonon, Neil Kelleher, Jonathan Keats, Jonathan D Licht
Loss or inactivation of the histone H3K27 demethylase UTX occurs in several malignancies, including multiple myeloma (MM). Using an isogenic cell system, we found that loss of UTX leads to deactivation of gene expression ultimately promoting the proliferation, clonogenicity, adhesion, and tumorigenicity of MM cells. Moreover, UTX mutant cells showed increased in vitro and in vivo sensitivity to inhibition of EZH2, a histone methyltransferase that generates H3K27me3. Such sensitivity was related to a decrease in the levels of IRF4 and c-MYC and an activation of repressors of IRF4 characteristic of germinal center B cells such as BCL6 and IRF1...
October 17, 2017: Cell Reports
https://www.readbyqxmd.com/read/29044419/myc-bcl2-co-expression-is-a-stronger-prognostic-factor-compared-with-the-cell-of-origin-classification-in-primary-cns-dlbcl
#20
Qian-Yun Shi, Xiao Feng, Wei Bao, Jie Ma, Jing-Huan Lv, Xuan Wang, Qiu Rao, Qun-Li Shi
Primary central nervous system (CNS) diffuse large B-cell lymphoma (DLBCL) is a subtype of DLBCL with an unfavorable prognosis and a poor response to the treatment. As we know, DLBCL is stratified into germinal center B-cell (GCB)-like and activated B-cell (ABC)-like subtypes with different prognosis according to their gene-expression characteristics. In this study, we analyzed a case series of 77 patients with primary CNS DLBCL. A difference in prognosis of GCB-like and ABC-like subtypes was noticed, but no statistical significance was found...
November 1, 2017: Journal of Neuropathology and Experimental Neurology
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