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https://www.readbyqxmd.com/read/28339425/potential-role-of-the-ovol1-ovol2-axis-and-c-myc-in-the-progression-of-cutaneous-squamous-cell-carcinoma
#1
Takamichi Ito, Gaku Tsuji, Fumitaka Ohno, Takeshi Nakahara, Hiroshi Uchi, Masutaka Furue
OVOL1 and OVOL2 are ubiquitously conserved genes encoding C2H2 zinc-finger transcription factors in mammals. They promote epithelial cell proliferation, differentiation, and mesenchymal-to-epithelial transition, coordinately mediated via the Wnt signaling pathway. We previously reported that human OVOL1 and OVOL2 were preferentially expressed in the normal epidermis and hair follicles as well as their tumors, and found that OVOL1 is upregulated in Bowen's disease and downregulated in cutaneous squamous cell carcinoma...
March 24, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28337018/rheumatoid-arthritis-fibroblast-like-synoviocyte-suppression-mediated-by-pten-involves-survivin-gene-silencing
#2
Danna Chen, Dongdong Liu, Dan Liu, Min He, Anping Peng, Jiarui Xu, Li Lin, Fudong Luo, Lin Chen, Xianzhang Huang, Junhua Zhuang, Jianhua Xu
Survivin is a proto-oncogene biomarker known for its anti-apoptotic and cell cycle regulating properties induced by the activation of the phosphoinositide 3-kinase (PI3K)/Akt pathway. In the context of non-cancer pathology, such as rheumatoid arthritis (RA), survivin has emerged as a feature associated with severe joint damage and poor treatment response. Phosphatase and tensin homolog (PTEN) is a phosphatase antagonizing all classes of PI3K. The interplay between survivin oncogenic mechanisms and proliferation suppression networks in RA has remained largely elusive...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28334365/effect-of-kit-and-pdgfra-mutations-on-survival-in-patients-with-gastrointestinal-stromal-tumors-treated-with-adjuvant-imatinib-an-exploratory-analysis-of-a-randomized-clinical-trial
#3
Heikki Joensuu, Eva Wardelmann, Harri Sihto, Mikael Eriksson, Kirsten Sundby Hall, Annette Reichardt, Jörg T Hartmann, Daniel Pink, Silke Cameron, Peter Hohenberger, Salah-Eddin Al-Batran, Marcus Schlemmer, Sebastian Bauer, Bengt Nilsson, Raija Kallio, Jouni Junnila, Aki Vehtari, Peter Reichardt
Importance: Little is known about whether the duration of adjuvant imatinib influences the prognostic significance of KIT proto-oncogene receptor tyrosine kinase (KIT) and platelet-derived growth factor receptor α (PDGFRA) mutations. Objective: To investigate the effect of KIT and PDGFRA mutations on recurrence-free survival (RFS) in patients with gastrointestinal stromal tumors (GISTs) treated with surgery and adjuvant imatinib. Design, Setting, and Participants: This exploratory study is based on the Scandinavian Sarcoma Group VIII/Arbeitsgemeinschaft Internistische Onkologie (SSGXVIII/AIO) multicenter clinical trial...
March 23, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28331559/tumor-suppressor-genes-in-familial-adenomatous-polyposis
#4
REVIEW
Nahal Eshghifar, Naser Farrokhi, Tahereh Naji, Mohammadreza Zali
Colorectal cancer (CRC) is mostly due to a series of genetic alterations that are being greatly under the influence of the environmental factors. These changes, mutational or epigenetic modifications at transcriptional forefront and/or post-transcriptional effects via miRNAs, include inactivation and the conversion of proto-oncogene to oncogenes, and/or inactivation of tumor suppressor genes (TSG). Here, a thorough review was carried out on the role of TSGs with the focus on the APC as the master regulator, mutated genes and mal-/dysfunctional pathways that lead to one type of hereditary form of the CRC; namely familial adenomatous polyposis (FAP)...
2017: Gastroenterology and Hepatology From Bed to Bench
https://www.readbyqxmd.com/read/28331449/cyclin-d1-in-the-liver-role-of-noncanonical-signaling-in-liver-steatosis-and-hormone-regulation
#5
Kelley G Núñez, Janet Gonzalez-Rosario, Paul T Thevenot, Ari J Cohen
BACKGROUND: Cyclin D1 is an important protein for cell cycle progression; however, functions independent of the cell cycle have been described in the liver. Cyclin D1 is also involved in DNA repair, is overexpressed in many cancers, and functions as a proto-oncogene. The lesser-known roles of Cyclin D1, specifically in hepatocytes, impact liver steatosis and hormone regulation in the liver. METHODS: A comprehensive search of PubMed was conducted using the keywords Cyclin D1, steatosis, lipogenesis, and liver transplantation...
2017: Ochsner Journal
https://www.readbyqxmd.com/read/28330874/high-resolution-3d-nmr-structure-of-the-kras-proto-oncogene-promoter-reveals-key-features-of-a-g-quadruplex-involved-in-transcriptional-regulation
#6
Abdelaziz Kerkour, Julien Marquevielle, Stefaniia Ivashchenko, Liliya A Yatsunyk, Jean-Louis Mergny, Gilmar F Salgado
Non-canonical base pairing within guanine-rich DNA and RNA sequences can produce G-quartets, whose stacking leads to the formation of a G-quadruplex (G4). G4s can coexist with canonical duplex DNA in the human genome and have been suggested to suppress gene transcription, and much attention has therefore focused on studying G4s in promotor regions of disease-related genes. For example, the human KRAS proto-oncogene contains a nuclease-hypersensitive element (1) located upstream of the major transcription start site...
March 22, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28329683/inactivation-of-ezh2-upregulates-gfi1-and-drives-aggressive-myc-driven-group-3-medulloblastoma
#7
BaoHan T Vo, Chunliang Li, Marc A Morgan, Ilan Theurillat, David Finkelstein, Shaela Wright, Judith Hyle, Stephanie M C Smith, Yiping Fan, Yong-Dong Wang, Gang Wu, Brent A Orr, Paul A Northcott, Ali Shilatifard, Charles J Sherr, Martine F Roussel
The most aggressive of four medulloblastoma (MB) subgroups are cMyc-driven group 3 (G3) tumors, some of which overexpress EZH2, the histone H3K27 mono-, di-, and trimethylase of polycomb-repressive complex 2. Ezh2 has a context-dependent role in different cancers as an oncogene or tumor suppressor and retards tumor progression in a mouse model of G3 MB. Engineered deletions of Ezh2 in G3 MBs by gene editing nucleases accelerated tumorigenesis, whereas Ezh2 re-expression reversed attendant histone modifications and slowed tumor progression...
March 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28327155/vasohibin-2-reduces-chemosensitivity-to-gemcitabine-in-pancreatic-cancer-cells-via-jun-proto-oncogene-dependent-transactivation-of-ribonucleotide-reductase-regulatory-subunit-m2
#8
Min Tu, Haifeng Li, Nan Lv, Chunhua Xi, Zipeng Lu, Jishu Wei, Jianmin Chen, Feng Guo, Kuirong Jiang, Guoxin Song, Wentao Gao, Yi Miao
BACKGROUND: Vasohibin 2 (VASH2) has previously been identified as an agiogenenic factor and a cancer related protein. Here we investigated the association of VASH2 expression and chemoresistance in pancreatic cancer. METHODS: Immunohistochemical staining for VASH2 was performed on 102 human pancreatic cancer samples. Pancreatic cancer cell line models exhibiting overexpression or knockdown of VASH2 were generated. Gene expression analyses were carried out to determine genes differentially regulated by VASH2...
March 21, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28325276/limiting-thymic-precursor-supply-increases-the-risk-of-lymphoid-malignancy-in-murine-x-linked-severe-combined-immunodeficiency
#9
Samantha L Ginn, Claus V Hallwirth, Sophia H Y Liao, Erdahl T Teber, Jonathan W Arthur, Jianmin Wu, Hong Ching Lee, Szun S Tay, Min Hu, Roger R Reddel, Matthew P McCormack, Adrian J Thrasher, Marina Cavazzana, Stephen I Alexander, Ian E Alexander
In early gene therapy trials for SCID-X1, using γ-retroviral vectors, T cell leukemias developed in a subset of patients secondary to insertional proto-oncogene activation. In contrast, we have reported development of T cell leukemias in SCID-X1 mice following lentivirus-mediated gene therapy independent of insertional mutagenesis. A distinguishing feature in our study was that only a proportion of transplanted γc-deficient progenitors were transduced and therefore competent for reconstitution. We hypothesized that reconstitution of SCID-X1 mice with limiting numbers of hematopoietic progenitors might be a risk factor for lymphoid malignancy...
March 17, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28323861/overexpression-of-c-jun-contributes-to-sorafenib-resistance-in-human-hepatoma-cell-lines
#10
Yuki Haga, Tatsuo Kanda, Masato Nakamura, Shingo Nakamoto, Reina Sasaki, Koji Takahashi, Shuang Wu, Osamu Yokosuka
BACKGROUND: Despite recent advances in treatment strategies, it is still difficult to cure patients with hepatocellular carcinoma (HCC). Sorafenib is the only approved multiple kinase inhibitor for systemic chemotherapy in patients with advanced HCC. The majority of advanced HCC patients are resistant to sorafenib. The mechanisms of sorafenib resistance are still unknown. METHODS: The expression of molecules involved in the mitogen-activated protein kinase (MAPK) signaling pathway in human hepatoma cell lines was examined in the presence or absence of sorafenib...
2017: PloS One
https://www.readbyqxmd.com/read/28323522/detection-of-cytosine-and-cpg-density-in-proto-oncogenes-and-tumor-suppressor-genes-in-promoter-sequences-of-acute-myeloid-leukemia
#11
Senol Dogan, Anis Cilic, Damir Marjanovic, Amina Kurtovic-Kozaric
Aberrant methylation is one of the driving forces of cancer genome development. Although the rate of methylation appears massively variable across the genome, it is mainly observed in histone modification, chromatin organization, DNA accessibility, or promoter sequence. Methylation of promoter sequence occurs mostly to cytosine nucleotides, which can affect transcription factors' binding affinities. In this study, we demonstrated that cytosine repeats (C types density), consisting of CC, CCC, CCCC, CCCCC, CCCCCC, CCCCCCC motifs and CpG islands density in 25 proto-oncogenes, tumor suppressor genes and control genes may play a role in the pathogenesis of acute myeloid leukemia...
March 21, 2017: Nucleosides, Nucleotides & Nucleic Acids
https://www.readbyqxmd.com/read/28316031/transactivation-domain-of-human-c-myc-is-essential-to-alleviate-poly-q-mediated-neurotoxicity-in-drosophila-disease-models
#12
Kritika Raj, Surajit Sarkar
Polyglutamine (poly(Q)) disorders, such as Huntington's disease (HD) and spinocerebellar ataxias, represent a group of neurological disorders which arise due to an atypically expanded poly(Q) tract in the coding region of the affected gene. Pathogenesis of these disorders inside the cells begins with the assembly of these mutant proteins in the form of insoluble inclusion bodies (IBs), which progressively sequester several vital cellular transcription factors and other essential proteins, and finally leads to neuronal dysfunction and apoptosis...
March 18, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28315378/epigenetic-regulation-of-ret-receptor-tyrosine-kinase-and-non-coding-rnas-in-mtc
#13
Lauren Jin Suk Joo, Jing Ting Zhao, Matti L Gild, Anthony R Glover, Stan B Sidhu
Medullary thyroid carcinoma (MTC) is an aggressive and rare cancer with limited treatment options for metastatic disease. Due to this, there is a need for a better understanding of MTC biology in the hope of improved treatments. One area of improved understanding of cancer biology is epigenetics. Epigenetics is defined as cellular processes which alter gene expression independent of changes in the primary DNA sequence. These processes include modifications such as DNA methylation, microRNA deregulation and post-translational histone modifications, all of which have been implicated in tumorigenesis of MTC...
March 14, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28303404/phylogenetic-analysis-of-proteins-involved-in-the-stringent-response-in-plant-cells
#14
Doshun Ito, Yuta Ihara, Hidenori Nishihara, Shinji Masuda
The nucleotide (p)ppGpp is a second messenger that controls the stringent response in bacteria. The stringent response modifies expression of a large number of genes and metabolic processes and allows bacteria to survive under fluctuating environmental conditions. Recent genome sequencing analyses have revealed that genes responsible for the stringent response are also found in plants. These include (p)ppGpp synthases and hydrolases, RelA/SpoT homologs (RSHs), and the pppGpp-specific phosphatase GppA/Ppx. However, phylogenetic relationship between enzymes involved in bacterial and plant stringent responses is as yet generally unclear...
March 16, 2017: Journal of Plant Research
https://www.readbyqxmd.com/read/28301528/genome-wide-mapping-of-histone-h3k9me2-in-acute-myeloid-leukemia-reveals-large-chromosomal-domains-associated-with-massive-gene-silencing-and-sites-of-genome-instability
#15
Anna C Salzberg, Abigail Harris-Becker, Evgenya Y Popova, Nikki Keasey, Thomas P Loughran, David F Claxton, Sergei A Grigoryev
A facultative heterochromatin mark, histone H3 lysine 9 dimethylation (H3K9me2), which is mediated by histone methyltransferases G9a/GLP (EHMT2/1), undergoes dramatic rearrangements during myeloid cell differentiation as observed by chromatin imaging. To determine whether these structural transitions also involve genomic repositioning of H3K9me2, we used ChIP-sequencing to map genome-wide topography of H3K9me2 in normal human granulocytes, normal CD34+ hematopoietic progenitors, primary myeloblasts from acute myeloid leukemia (AML) patients, and a model leukemia cell line K562...
2017: PloS One
https://www.readbyqxmd.com/read/28300754/effects-of-light-emitting-diode-irradiation-on-growth-characteristics-and-regulation-of-porphyrin-biosynthesis-in-rice-seedlings
#16
Lien Hong Tran, Sunyo Jung
We examined the effects of light quality on growth characteristics and porphyrin biosynthesis of rice seedlings grown under different wavelengths from light emitting diodes (LEDs). After 10 days of exposure to various wavelengths of LEDs, leaf area and shoot biomass were greater in seedlings grown under white and blue LEDs than those of green and red LEDs. Both green and red LED treatments drastically decreased levels of protoporphyrin IX (Proto IX) and Mg-porphyrins compared to those of white LED, while levels of Mg-Proto IX monomethyl ester and protochlorophyllide under blue LED were decreased by 21% and 49%, respectively...
March 16, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28298901/unveiling-another-missing-piece-in-ebv-driven-lymphomagenesis-ebv-encoded-micrornas-expression-in-eber-negative-burkitt-lymphoma-cases
#17
Lucia Mundo, Maria R Ambrosio, Matteo Picciolini, Giuseppe Lo Bello, Sara Gazaneo, Leonardo Del Porro, Stefano Lazzi, Mohsen Navari, Noel Onyango, Massimo Granai, Cristiana Bellan, Giulia De Falco, Davide Gibellini, Pier P Piccaluga, Lorenzo Leoncini
Epstein-Barr virus (EBV) is a gammaherpesvirus linked to a number of lymphoid and epithelial malignancies, including Burkitt lymphoma (BL) in which its frequency ranges from 30% in sporadic cases to 100% in the endemic ones. The possible contribution of EBV to BL pathogenesis is largely unknown. It has been suggested that EBV may be associated with all of the cases, including those diagnosed as EBV negative by a mechanism of hit-and-run. Early during oncogenesis, viral genes are essential for initiating disease...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28294470/exome-sequencing-deciphers-a-germline-met-mutation-in-familial-epidermal-growth-factor-receptor-mutant-lung-cancer
#18
Naoki Tode, Toshiaki Kikuchi, Tomohiro Sakakibara, Taizou Hirano, Akira Inoue, Shinya Ohkouchi, Tsutomu Tamada, Tatsuma Okazaki, Akira Koarai, Hisatoshi Sugiura, Tetsuya Niihori, Yoko Aoki, Keiko Nakayama, Kunio Matsumoto, Yoichi Matsubara, Masayuki Yamamoto, Akira Watanabe, Toshihiro Nukiwa, Masakazu Ichinose
Lung cancer accompanied by somatic activating mutations in the epidermal growth factor receptor (EGFR) gene, which is associated with a significant clinical response to the targeted therapy, is frequently found in never-smoking Asian women with adenocarcinoma. Although this implies genetic factors underlying the carcinogenesis, the etiology remains unclear. To gain insight into the pathogenic mechanisms, we sequenced the exomes in the peripheral-blood DNA from six siblings, four affected and two unaffected siblings, of a kindred with familial EGFR-mutant lung adenocarcinoma...
March 13, 2017: Cancer Science
https://www.readbyqxmd.com/read/28288693/uterine-epithelioid-leiomyosarcoma-with-c-kit-expression-and-ywhae-gene-rearrangement-a-case-report-of-a-diagnostic-pitfall-of-uterine-sarcoma
#19
Terufumi Kubo, Shintaro Sugita, Ryuichi Wada, Noriaki Kikuchi, Masahiro Iwasaki, Yumika Ito, Taro Sugawara, Hiromi Fujita, Makoto Emori, Ryoichi Tanaka, Hiroshi Hirano, Tsuyoshi Saito, Tadashi Hasegawa
BACKGROUND: Uterine sarcoma is a rare tumor that is often difficult to classify based on morphological and immunohistochemical analysis alone. Limited access to molecular biological analysis in routine practice would hinder making a definitive diagnosis. CASE PRESENTATION: In this report, we describe a case of a mesenchymal tumor arising from the uterine cervix in a 52-year-old woman. From microscopic morphology of the resected specimen, epithelioid leiomyosarcoma, high-grade endometrial stromal sarcoma, or uterine gastrointestinal stromal tumor (GIST) were considered as differential diagnoses...
March 14, 2017: Diagnostic Pathology
https://www.readbyqxmd.com/read/28288113/germline-mutations-in-abl1-cause-an-autosomal-dominant-syndrome-characterized-by-congenital-heart-defects-and-skeletal-malformations
#20
Xia Wang, Wu-Lin Charng, Chun-An Chen, Jill A Rosenfeld, Aisha Al Shamsi, Lihadh Al-Gazali, Marianne McGuire, Nicholas Ah Mew, Georgianne L Arnold, Chunjing Qu, Yan Ding, Donna M Muzny, Richard A Gibbs, Christine M Eng, Magdalena Walkiewicz, Fan Xia, Sharon E Plon, James R Lupski, Christian P Schaaf, Yaping Yang
ABL1 is a proto-oncogene well known as part of the fusion gene BCR-ABL1 in the Philadelphia chromosome of leukemia cancer cells. Inherited germline ABL1 changes have not been associated with genetic disorders. Here we report ABL1 germline variants cosegregating with an autosomal dominant disorder characterized by congenital heart disease, skeletal abnormalities, and failure to thrive. The variant c.734A>G (p.Tyr245Cys) was found to occur de novo or cosegregate with disease in five individuals (families 1-3)...
March 13, 2017: Nature Genetics
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