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https://www.readbyqxmd.com/read/28426730/functional-genetic-variant-of-ww-domain-containing-oxidoreductase-wwox-gene-is-associated-with-hepatocellular-carcinoma-risk
#1
Hsiang-Lin Lee, Hsin-Lin Cheng, Yu-Fan Liu, Ming-Chih Chou, Shun-Fa Yang, Ying-Erh Chou
BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. Human WW domain-containing oxidoreductase (WWOX) gene has been identified as a tumor suppressor gene in multiple cancers. We hypothesize that genetic variations in WWOX are associated with HCC risk. METHODOLOGY/PRINCIPAL FINDINGS: Five single-nucleotide polymorphisms (SNPs) of the WWOX gene were evaluated from 708 normal controls and 354 patients with HCC. We identified a significant association between a WWOX single nucleotide polymorphism (SNP), rs73569323, and decreased risk of HCC...
2017: PloS One
https://www.readbyqxmd.com/read/28386190/establishment-of-apoptotic-regulatory-network-for-genetic-markers-of-colorectal-cancer-and-optimal-selection-of-traditional-chinese-medicine-target
#2
Tongde Tian, Chuanliang Chen, Feng Yang, Jingwen Tang, Junwen Pei, Bian Shi, Ning Zhang, Jianhua Zhang
The paper aimed to screen out genetic markers applicable to early diagnosis for colorectal cancer and establish apoptotic regulatory network model for colorectal cancer, and to analyze the current situation of traditional Chinese medicine (TCM) target, thereby providing theoretical evidence for early diagnosis and targeted therapy of colorectal cancer. Taking databases including CNKI, VIP, Wanfang data, Pub Med, and MEDLINE as main sources of literature retrieval, literatures associated with genetic markers that are applied to early diagnosis of colorectal cancer were searched and performed comprehensive and quantitative analysis by Meta analysis, hence screening genetic markers used in early diagnosis of colorectal cancer...
March 2017: Saudi Journal of Biological Sciences
https://www.readbyqxmd.com/read/28386169/establishment-of-apoptotic-regulatory-network-for-genetic-markers-of-colorectal-cancer
#3
Yibin Hao, Guoyong Shan, Kejun Nan
Our purpose is to screen out genetic markers applicable to early diagnosis for colorectal cancer and to establish apoptotic regulatory network model for colorectal cancer, thereby providing theoretical evidence and targeted therapy for early diagnosis of colorectal cancer. Taking databases including CNKI, VIP, Wanfang data, Pub Med, and MEDLINE as main sources of literature retrieval, literatures associated with genetic markers applied to early diagnosis of colorectal cancer were searched to perform comprehensive and quantitative analysis by Meta analysis, hence screening genetic markers used in early diagnosis of colorectal cancer...
March 2017: Saudi Journal of Biological Sciences
https://www.readbyqxmd.com/read/28373548/editorial-expression-of-concern-wwox-gene-restoration-prevents-lung-cancer-growth-in-vitro-and-in-vivo
#4
(no author information available yet)
No abstract text is available yet for this article.
April 3, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28283473/loss-of-lung-wwox-expression-causes-neutrophilic-inflammation
#5
Sunit Singla, Jiwang Chen, Shruthi Sethuraman, Justin R Sysol, Amulya Gampa, Shuangping Zhao, Roberto F Machado
The tumor suppressor, WWOX, exhibits regulatory interactions with an array of transcription factors and signaling molecules that are positioned at the well-known crossroads between inflammation and cancer. WWOX is also subject to downregulation by genotoxic environmental exposures, making it of potential interest to the study of lung pathobiology. Knockdown of lung WWOX expression in mice was observed to cause neutrophil influx, and accompanied by a corresponding vascular leak and inflammatory cytokine production...
March 10, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28280357/a-new-tumor-suppressor-lncrna-rp11-190d6-2-inhibits-the-proliferation-migration-and-invasion-of-epithelial-ovarian-cancer-cells
#6
Wenxian Tong, Liu Yang, Qiang Yu, Jie Yao, Anbing He
At present, a large number of long noncoding RNAs (lncRNAs) from the human genome have been discovered. Meanwhile, emerging evidence has indicated that lncRNAs could play a critical role in the regulation of cellular processes such as cancer progression and metastasis. However, the functions of some new lncRNAs in the complex transcriptional process are mostly unknown at present. Existing studies suggest that loss of WW domain-containing oxidoreductase (WWOX) expression is linked with poor prognosis in numerous cancers, including epithelial ovarian cancer (EOC)...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28199992/fragile-genes-that-are-frequently-altered-in-cancer-players-not-passengers
#7
REVIEW
Jenna R Karras, Morgan S Schrock, Bahadir Batar, Kay Huebner
FHIT, located at FRA3B, is one of the most commonly deleted genes in human cancers, and loss of FHIT protein is one of the earliest events in cancer initiation. However, location of FHIT at a chromosomal fragile site, a locus prone to breakage and gap formation under even mild replication stress, has encouraged claims that FHIT loss is a passenger event in cancers. We summarize accumulated evidence that FHIT protein functions as a genome "caretaker" required to protect the stability of genomes of normal cells of most tissues from agents causing intrinsic and extrinsic DNA damage...
2016: Cytogenetic and Genome Research
https://www.readbyqxmd.com/read/28151481/epigenetic-regulation-of-hgf-met-receptor-axis-is-critical-for-the-outgrowth-of-bone-metastasis-from-breast-carcinoma
#8
Paola Bendinelli, Paola Maroni, Emanuela Matteucci, Maria Alfonsina Desiderio
Our translational research deals with the influence of microenvironment on the phenotype and colonization of bone metastases from breast carcinoma, and on pre-metastatic niche formation. The aim of the present study was to clarify the origin of hepatocyte growth factor (HGF), ligand of Met receptor, the control of the axis HGF/Met by DNA methylation, and its importance for the nexus supportive cells-metastatic cells and for metastasis outgrowth. In bone metastasis of the 1833-xenograft model, DNA methyltransferase blockade using the chemotherapic drug 5-aza-2'-deoxycytidine (decitabine) strongly reduced the expression of HGF/Met receptor axis and of E-cadherin, with decrease of metastasis wideness and osteolysis, prolonging mice survival...
February 2, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28130116/diagnostic-yield-of-targeted-gene-panel-sequencing-to-identify-the-genetic-etiology-of-disorders-of-sex-development
#9
Ja Hye Kim, Eungu Kang, Sun Hee Heo, Gu-Hwan Kim, Ja-Hyun Jang, Eun-Hae Cho, Beom Hee Lee, Han-Wook Yoo, Jin-Ho Choi
Disorders of sex development (DSD) vary phenotypically and are caused by a number of genetic etiologies. This study investigated the genetic etiology of DSD patients using targeted exome sequencing of 67 known DSD-associated genes in humans. This study included 37 patients with 46, XY DSD and seven patients with 46, XX DSD. We identified known pathogenic mutations or deletion in nine (20.5%) patients in the AR, CYP17A1, SRD5A1, and DMRT1/2 genes. Novel variants were identified in nine patients (20.5%) in the AR, ATRX, CYP17A1, CHD7, MAP3K1, NR5A1, and WWOX genes...
January 24, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28045433/functions-and-epigenetic-regulation-of-wwox-in-bone-metastasis-from-breast-carcinoma-comparison-with-primary-tumors
#10
REVIEW
Paola Maroni, Emanuela Matteucci, Paola Bendinelli, Maria Alfonsina Desiderio
Epigenetic mechanisms influence molecular patterns important for the bone-metastatic process, and here we highlight the role of WW-domain containing oxidoreductase (Wwox). The tumor-suppressor Wwox lacks in almost all cancer types; the variable expression in osteosarcomas is related to lung-metastasis formation, and exogenous Wwox destabilizes HIF-1α (subunit of Hypoxia inducible Factor-1, HIF-1) affecting aerobic glycolysis. Our recent studies show critical functions of Wwox present in 1833-osteotropic clone, in the corresponding xenograft model, and in human bone metastasis from breast carcinoma...
January 1, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27999774/hyal-2-wwox-smad4-signaling-in-cell-death-and-anticancer-response
#11
REVIEW
Li-Jin Hsu, Ming-Fu Chiang, Chun-I Sze, Wan-Pei Su, Ye Vone Yap, I-Ting Lee, Hsiang-Ling Kuo, Nan-Shan Chang
Hyaluronidase HYAL-2 is a membrane-anchored protein and also localizes, in part, in the lysosome. Recent study from animal models revealed that both HYAL-1 and HYAL-2 are essential for the metabolism of hyaluronan (HA). Hyal-2 deficiency is associated with chronic thrombotic microangiopathy with hemolytic anemia in mice due to over accumulation of high molecular size HA. HYAL-2 is essential for platelet generation. Membrane HYAL-2 degrades HA bound by co-receptor CD44. Also, in a non-canonical signal pathway, HYAL-2 serves as a receptor for transforming growth factor beta (TGF-β) to signal with downstream tumor suppressors WWOX and SMAD4 to control gene transcription...
2016: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/27869163/wwox-brca1-interaction-role-in-dna-repair-pathway-choice
#12
M S Schrock, B Batar, J Lee, T Druck, B Ferguson, J H Cho, K Akakpo, H Hagrass, N A Heerema, F Xia, J D Parvin, C M Aldaz, K Huebner
In this study, loss of expression of the fragile site-encoded Wwox protein was found to contribute to radiation and cisplatin resistance of cells, responses that could be associated with cancer recurrence and poor outcome. WWOX gene deletions occur in a variety of human cancer types, and reduced Wwox protein expression can be detected early during cancer development. We found that Wwox loss is followed by mild chromosome instability in genomes of mouse embryo fibroblast cells from Wwox-knockout mice. Human and mouse cells deficient for Wwox also exhibit significantly enhanced survival of ionizing radiation and bleomycin treatment, agents that induce double-strand breaks (DSBs)...
April 20, 2017: Oncogene
https://www.readbyqxmd.com/read/27845895/hyaluronan-activates-hyal-2-wwox-smad4-signaling-and-causes-bubbling-cell-death-when-the-signaling-complex-is-overexpressed
#13
Li-Jin Hsu, Qunying Hong, Shur-Tzu Chen, Hsiang-Lin Kuo, Lori Schultz, John Heath, Sing-Ru Lin, Ming-Hui Lee, Dong-Zhang Li, Zih-Ling Li, Hui-Ching Cheng, Gerard Armand, Nan-Shan Chang
Malignant cancer cells frequently secrete significant amounts of transforming growth factor beta (TGF-β), hyaluronan (HA) and hyaluronidases to facilitate metastasizing to target organs. In a non-canonical signaling, TGF-β binds membrane hyaluronidase Hyal-2 for recruiting tumor suppressors WWOX and Smad4, and the resulting Hyal-2/WWOX/Smad4 complex is accumulated in the nucleus to enhance SMAD-promoter dependent transcriptional activity. Yeast two-hybrid analysis showed that WWOX acts as a bridge to bind both Hyal-2 and Smad4...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/27834355/wwox-inhibits-the-invasion-of-lung-cancer-cells-by-downregulating-runx2
#14
Q-W Zheng, Y-L Zhou, Q-J You, F Shou, Q-F Pang, J-L Chen
The WW domain-containing oxidoreductase (WWOX) is a tumor suppressor that is lost or decreased in most human tumors. The role of WWOX in human lung carcinoma invasion is still not clear. This study aimed to elucidate the potential role of WWOX in lung cancer cell invasion. WWOX mRNA levels in human lung cancers and lung cancer cell lines were assayed by quantitative real-time PCR. WWOX in lung cancer cell lines was manipulated by transfection of expression vector or small interfering RNA. Cell migration and invasion were assessed by wound healing and/or transwell migration and invasion assays...
December 2016: Cancer Gene Therapy
https://www.readbyqxmd.com/read/27773744/fhit-and-wwox-loss-associated-genome-instability-a-genome-caretaker-one-two-punch
#15
Morgan S Schrock, Jenna R Karras, Matthew J Guggenbiller, Teresa Druck, Bahadir Batar, Kay Huebner
Expression of Fhit and Wwox protein is frequently lost or reduced in many human cancers. In this report, we provide data that further characterizes the molecular consequences of Fhit loss in the initiation of DNA double-strand breaks (DSBs), and of Wwox loss in altered repair of DSBs. We show that loss of Fhit initiates mild genome instability in early passage mouse kidney cells, confirming that DNA damage associated with Fhit-deficiency is not limited to cancer cells. We also demonstrate that the cause of Fhit-deficient DSBs: thymidine deficiency-induced replication stress, can be resolved with thymidine supplementation in early passage mouse kidney cells before extensive genome instability occurs...
September 26, 2016: Advances in Biological Regulation
https://www.readbyqxmd.com/read/27596295/genetic-diversity-of-urinary-bladder-cancer-and-the-risk-of-recurrence-based-on-mutation-analysis
#16
M Traczyk-Borszynska, E Borkowska, Z Jablonowski, A Jedrzejczyk, M Pietrusinski, B Kaluzewski, M Sosnowski, M Borowiec
The aim of the study was to assess the genetic diversity of bladder cancer and determine the suitability of a proposed molecular marker panel to monitor the course of bladder cancer patients. The study involved 185 patients with diagnosed bladder cancer. The genetic diversity of the bladder cancer was evaluated by the prevalence of mutations in the TP53, HRAS, FGFR3 and WWOX genes. Mutations were detected in 62.2% of the tumor samples. The most frequently mutated genes were FGFR3 (49.7%) and TP53 (16.2%). No mutation was observed in the WWOX gene...
2016: Neoplasma
https://www.readbyqxmd.com/read/27572307/oncogenic-roles-of-the-setdb2-histone-methyltransferase-in-gastric-cancer
#17
Taketo Nishikawaji, Yoshimitsu Akiyama, Shu Shimada, Kazuyuki Kojima, Tatsuyuki Kawano, Yoshinobu Eishi, Yasuhito Yuasa, Shinji Tanaka
SETDB2 is a histone H3 lysine 9 (H3K9) tri-methyltransferase that is involved in transcriptional gene silencing. Since it is still unknown whether SETDB2 is linked to carcinogenesis, we studied alterations and functions of SETDB2 in human gastric cancers (GCs). SETDB2 protein was highly expressed in 30 of 72 (41.7%) primary GC tissues compared with their normal counterparts by immunohistochemistry. SETDB2 overexpression was significantly associated with the late stage of GCs (P<0.05) and poor prognosis of GC patients (P<0...
October 11, 2016: Oncotarget
https://www.readbyqxmd.com/read/27569545/rare-inherited-and-de-novo-cnvs-reveal-complex-contributions-to-asd-risk-in-multiplex-families
#18
Virpi M Leppa, Stephanie N Kravitz, Christa Lese Martin, Joris Andrieux, Cedric Le Caignec, Dominique Martin-Coignard, Christina DyBuncio, Stephan J Sanders, Jennifer K Lowe, Rita M Cantor, Daniel H Geschwind
Rare mutations, including copy-number variants (CNVs), contribute significantly to autism spectrum disorder (ASD) risk. Although their importance has been established in families with only one affected child (simplex families), the contribution of both de novo and inherited CNVs to ASD in families with multiple affected individuals (multiplex families) is less well understood. We analyzed 1,532 families from the Autism Genetic Resource Exchange (AGRE) to assess the impact of de novo and rare CNVs on ASD risk in multiplex families...
September 1, 2016: American Journal of Human Genetics
https://www.readbyqxmd.com/read/27550453/wwox-and-p53-dysregulation-synergize-to-drive-the-development-of-osteosarcoma
#19
Sara Del Mare, Hussam Husanie, Ortal Iancu, Mohammad Abu-Odeh, Konstantinos Evangelou, Francesca Lovat, Stefano Volinia, Jonathan Gordon, Gail Amir, Janet Stein, Gary S Stein, Carlo M Croce, Vassilis Gorgoulis, Jane B Lian, Rami I Aqeilan
Osteosarcoma is a highly metastatic form of bone cancer in adolescents and young adults that is resistant to existing treatments. Development of an effective therapy has been hindered by very limited understanding of the mechanisms of osteosarcomagenesis. Here, we used genetically engineered mice to investigate the effects of deleting the tumor suppressor Wwox selectively in either osteoblast progenitors or mature osteoblasts. Mice with conditional deletion of Wwox in preosteoblasts (Wwox(Δosx1)) displayed a severe inhibition of osteogenesis accompanied by p53 upregulation, effects that were not observed in mice lacking Wwox in mature osteoblasts...
October 15, 2016: Cancer Research
https://www.readbyqxmd.com/read/27501229/genomic-alteration-in-head-and-neck-squamous-cell-carcinoma-hnscc-cell-lines-inferred-from-karyotyping-molecular-cytogenetics-and-array-comparative-genomic-hybridization
#20
Worapong Singchat, Ekarat Hitakomate, Budsaba Rerkarmnuaychoke, Aorarat Suntronpong, Beiyuan Fu, Winai Bodhisuwan, Surin Peyachoknagul, Fengtang Yang, Sittichai Koontongkaew, Kornsorn Srikulnath
Genomic alteration in head and neck squamous cell carcinoma (HNSCC) was studied in two cell line pairs (HN30-HN31 and HN4-HN12) using conventional C-banding, multiplex fluorescence in situ hybridization (M-FISH), and array comparative genomic hybridization (array CGH). HN30 and HN4 were derived from primary lesions in the pharynx and base of tongue, respectively, and HN31 and HN12 were derived from lymph-node metastatic lesions belonging to the same patients. Gain of chromosome 1, 7, and 11 were shared in almost all cell lines...
2016: PloS One
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