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https://www.readbyqxmd.com/read/28655161/dysfunction-of-pla2g6-and-cyp2c44-associated-network-signals-imminent-carcinogenesis-from-chronic-inflammation-to-hepatocellular-carcinoma
#1
Meiyi Li, Chen Li, Wei-Xin Liu, Conghui Liu, Jingru Cui, Qingrun Li, Hong Ni, Yingcheng Yang, Chaochao Wu, Chunlei Chen, Xing Zhen, Tao Zeng, Mujun Zhao, Lei Chen, Jiarui Wu, Rong Zeng, Luonan Chen
Little is known about how chronic inflammation contributes to the progression of hepatocellular carcinoma (HCC), especially the initiation of cancer. To uncover the critical transition from chronic inflammation to HCC and the molecular mechanisms at a network level, we analyzed the time-series proteomic data of woodchuck hepatitis virus/c-myc mice and age-matched wt-C57BL/6 mice using our dynamical network biomarker (DNB) model. DNB analysis indicated that the 5th month after birth of transgenic mice was the critical period of cancer initiation, just before the critical transition, which is consistent with clinical symptoms...
June 26, 2017: Journal of Molecular Cell Biology
https://www.readbyqxmd.com/read/28654902/cryptotanshinone-inhibits-proliferation-yet-induces-apoptosis-by-suppressing-stat3-signals-in-renal-cell-carcinoma
#2
Zhiguo Chen, Rujian Zhu, Jiayi Zheng, Chen Chen, Chi Huang, Junjie Ma, Chen Xu, Wei Zhai, Junhua Zheng
It has been established that signal transducer and activator of transcription 3 serves as an oncoprotein in various human cancers; targeting it is therefore a reasonable approach for emerging cancer therapies. Cryptotanshinone, a natural compound extracted from the root of Salvia miltiorrhiza Bunge, has been identified as a potential STAT3 inhibitor. However, its functional role in renal cell carcinomas remains largely unknown. Therefore, we investigated the mode of action for cryptotanshinone. We found that cryptotanshinone substantially suppressed cancer cell growth while it promoted cell apoptosis by inhibiting the phosphorylation of STAT3 at Tyr705 and its blocking nuclear translocation...
June 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28653878/sirtuin-6-plays-an-oncogenic-role-and-induces-cell-autophagy-in-esophageal-cancer-cells
#3
Nan Huang, Zhiwei Liu, Jiabei Zhu, Zhongqi Cui, Yuguang Li, Yongchun Yu, Fenyong Sun, Qiuhui Pan, Qingyuan Yang
Sirtuin 6, a member of sirtuin family, is generally regarded as a tumor suppressor as it participates in suppressing hypoxia-inducible factor 1α and MYC transcription activity by deacetylating H3K9 (histone H3 lysine 9) and H3K56 (histone H3 lysine) at promoters of target genes, leading to the aerobic glycolysis inhibition and cell growth suppression. However, its expression has recently been reported to be highly elevated in a series of tumors, including prostate cancer, breast cancer, and non-small cell lung cancer, indicating that sirtuin 6 plays dual roles in tumorigenicity in a cell/tumor type-specific manner...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28653607/overexpression-of-glutathione-s-transferase-p1-inhibits-the-viability-and-motility-of-prostate-cancer-via-targeting-myc-and-inactivating-the-mek-erk1-2-pathways
#4
Xiu-Xin Wang, Hong-Tao Jia, Hua Yang, Mao-Hua Luo, Tao Sun
Prostate cancer (PC) is one of the most common malignancies of men. Glutathione S-transferase P1 (GSTP1) has been suggested to play a protective role in the prostate. The proto-oncogene MYC has been extensively proved to be a key regulator of tumor transformation from early stage to malignant. Our study aims to investigate the mechanism of GSTP1 in the biological behavior of PC. Compared with normal prostate tissues, the expression of GSTP1 was decreased in PC tissues. Conversely, the level of MYC was increased in PC tissues compared with normal tissues...
June 19, 2017: Oncology Research
https://www.readbyqxmd.com/read/28653353/preclinical-evaluation-of-the-bet-bromodomain-inhibitor-bay-1238097-for-the-treatment-of-lymphoma
#5
Elena Bernasconi, Eugenio Gaudio, Pascale Lejeune, Chiara Tarantelli, Luciano Cascione, Ivo Kwee, Filippo Spriano, Andrea Rinaldi, Afua A Mensah, Elaine Chung, Anastasios Stathis, Stephan Siegel, Norbert Schmees, Matthias Ocker, Emanuele Zucca, Bernard Haendler, Francesco Bertoni
The epigenome is often deregulated in cancer and treatment with inhibitors of bromodomain and extra-terminal proteins, the readers of epigenetic acetylation marks, represents a novel therapeutic approach. Here, we have characterized the anti-tumour activity of the novel bromodomain and extra-terminal (BET) inhibitor BAY 1238097 in preclinical lymphoma models. BAY 1238097 showed anti-proliferative activity in a large panel of lymphoma-derived cell lines, with a median 50% inhibitory concentration between 70 and 208 nmol/l...
June 27, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28653191/microrna-dysregulation-to-identify-novel-therapeutic-targets
#6
Carlo M Croce
This paper describes how we discovered the juxtaposition of the MYC gene to the human immunoglobulin loci and how that finding was extended to characterize molecularly the t(14;18) chromosome translocation of follicular lymphoma and to clone the BCL2 gene. BCL2 is also overexpressed in CLL, the most common human leukemia. We discovered that most of human CLLs have a deletion of two microRNAs residing in the same polycistronic RNA, miR-15a and miR-16-1, and that these two microRNAs are negative regulators of BCL2...
June 27, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28652407/arginine-methylation-regulates-c-myc-dependent-transcription-by-altering-promoter-recruitment-of-the-acetyltransferase-p300
#7
Irina Tikhanovich, Jie Zhao, Brian Bridges, Sean Kumer, Ben Roberts, Steven A Weinman
Protein arginine methyltransferase 1 (PRMT1) is an essential gene controlling about 85% of total cellular arginine methylation in proteins. We have previously shown that PRMT1 is an important regulator of innate immune responses and that it is required for M2 macrophage differentiation. c-Myc is a transcription factor that is critical in regulating cell proliferation and also regulates the M2 transcriptional program in macrophages. Here, we sought to determine whether c-Myc in myeloid cells is regulated by PRMT1-dependent arginine methylation...
June 26, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28651973/1-25-oh-2d3-disrupts-glucose-metabolism-in-prostate-cancer-cells-leading-to-a-truncation-of-the-tca-cycle-and-inhibition-of-txnip-expression
#8
Mohamed A Abu El Maaty, Hamed Alborzinia, Shehryar J Khan, Michael Büttner, Stefan Wölfl
Prostate cell metabolism exhibits distinct profiles pre- and post-malignancy. The malignant metabolic shift converts prostate cells from "citrate-producing" to "citrate-oxidizing" cells, thereby enhancing glucose metabolism, a phenotype that contrasts classical tumoral Warburg metabolism. An on-line biosensor chip system (BIONAS 2500) was used to monitor metabolic changes (glycolysis and respiration) in response to the putative anti-cancer nutraceutical 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], in different prostate cancer (PCa) cell lines (LNCaP, VCaP, DU145 and PC3)...
June 23, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28651018/meta-analysis-of-mirna-expression-profiles-for-prostate-cancer-recurrence-following-radical-prostatectomy
#9
Elnaz Pashaei, Elham Pashaei, Maryam Ahmady, Mustafa Ozen, Nizamettin Aydin
BACKGROUND: Prostate cancer (PCa) is a leading reason of death in men and the most diagnosed malignancies in the western countries at the present time. After radical prostatectomy (RP), nearly 30% of men develop clinical recurrence with high serum prostate-specific antigen levels. An important challenge in PCa research is to identify effective predictors of tumor recurrence. The molecular alterations in microRNAs are associated with PCa initiation and progression. Several miRNA microarray studies have been conducted in recurrence PCa, but the results vary among different studies...
2017: PloS One
https://www.readbyqxmd.com/read/28650479/aml1-eto-requires-enhanced-c-d-box-snorna-rnp-formation-to-induce-self-renewal-and-leukaemia
#10
Fengbiao Zhou, Yi Liu, Christian Rohde, Cornelius Pauli, Dennis Gerloff, Marcel Köhn, Danny Misiak, Nicole Bäumer, Chunhong Cui, Stefanie Göllner, Thomas Oellerich, Hubert Serve, Maria-Paz Garcia-Cuellar, Robert Slany, Jaroslaw P Maciejewski, Bartlomiej Przychodzen, Barbara Seliger, Hans-Ulrich Klein, Christoph Bartenhagen, Wolfgang E Berdel, Martin Dugas, Makoto Mark Taketo, Daneyal Farouq, Schraga Schwartz, Aviv Regev, Josée Hébert, Guy Sauvageau, Caroline Pabst, Stefan Hüttelmaier, Carsten Müller-Tidow
Leukaemogenesis requires enhanced self-renewal, which is induced by oncogenes. The underlying molecular mechanisms remain incompletely understood. Here, we identified C/D box snoRNAs and rRNA 2'-O-methylation as critical determinants of leukaemic stem cell activity. Leukaemogenesis by AML1-ETO required expression of the groucho-related amino-terminal enhancer of split (AES). AES functioned by inducing snoRNA/RNP formation via interaction with the RNA helicase DDX21. Similarly, global loss of C/D box snoRNAs with concomitant loss of rRNA 2'-O-methylation resulted in decreased leukaemia self-renewal potential...
June 26, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28650023/ligand-induced-conformational-preorganization-of-loops-of-c-myc-g-quadruplex-dna-and-its-implications-in-structure-specific-drug-design
#11
S Harikrishna, Saikiran Kotaru, P I Pradeepkumar
Stabilization of a G-quadruplex (G4) DNA structure in the proto-oncogene c-MYC using small molecule ligands has emerged as an attractive strategy for the development of anticancer therapeutics. To understand the subtle structural changes in the G4 structure upon ligand binding, molecular dynamics (MD) simulations of c-MYC G4 DNA were carried out in a complex with six different potent ligands: 3AQN, 6AQN, 3APN, 360A, Nap-Et, and Nap-Pr. The results show that the ligands 3AQN, 6AQN, 3APN, and 360A stabilize the G4 structure by making stacking interactions with the top quartet...
June 26, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28649719/regulation-of-growth-defense-balance-by-the-jasmonate-zim-domain-jaz-myc-transcriptional-module
#12
Ian T Major, Yuki Yoshida, Marcelo L Campos, George Kapali, Xiu-Fang Xin, Koichi Sugimoto, Dalton de Oliveira Ferreira, Sheng Yang He, Gregg A Howe
The plant hormone jasmonate (JA) promotes the degradation of JASMONATE ZIM-DOMAIN (JAZ) proteins to relieve repression on diverse transcription factors (TFs) that execute JA responses. However, little is known about how combinatorial complexity among JAZ-TF interactions maintains control over myriad aspects of growth, development, reproduction, and immunity. We used loss-of-function mutations to define epistatic interactions within the core JA signaling pathway and to investigate the contribution of MYC TFs to JA responses in Arabidopsis thaliana...
June 26, 2017: New Phytologist
https://www.readbyqxmd.com/read/28648593/myc-rearranged-lymphomas-other-than-burkitt-comparison-between-r-chop-and-burkitt-type-immunochemotherapy
#13
Maria Joao Baptista, Gustavo Tapia, José-Ángel Hernández-Rivas, Alejandra Martínez-Trillos, José-Luis Mate, José-Tomás Navarro
BACKGROUND AND OBJECTIVE: MYC-rearranged (MYC-R) lymphomas other than Burkitt lymphoma (BL) are very aggressive, with poor prognosis when treated with standard regimens. We aimed to study the characteristics and outcome of a series of MYC-R lymphomas comparing the treatment results between R-CHOP based and a specific intensive regimen for BL (BURKIMAB). PATIENTS AND METHODS: Retrospective study of patients diagnosed with MYC-R. Translocations of MYC, BCL2 and BCL6 were evaluated by fluorescent in situ hybridization...
June 22, 2017: Medicina Clínica
https://www.readbyqxmd.com/read/28647646/the-secreted-protein-wnt5a-regulates-condylar-chondrocyte-proliferation-hypertrophy-and-migration
#14
Xianpeng Ge, Ruirui Shi, Xuchen Ma
OBJECTIVE: Our previous study showed that WNT5A, a member of the noncanonical WNT pathway, is involved in interleukin-1beta induced matrix metalloproteinase expression in temporomandibular joint (TMJ) condylar chondrocytes. The purpose of this study is to further explore the roles of WNT5A in cartilage biology of the TMJ. METHODS: An early TMJ osteoarthritis-like rat model was constructed by a mechanical method (steady mouth-opening). The gene and protein levels of WNT5A during the condylar cartilage changes were measured...
June 16, 2017: Archives of Oral Biology
https://www.readbyqxmd.com/read/28646927/hoxb7-accelerates-the-malignant-progression-of-hepatocellular-carcinoma-by-promoting-stemness-and-epithelial-mesenchymal-transition
#15
Hong-Bo Huan, Da-Peng Yang, Xu-Dong Wen, Xue-Jiao Chen, Liang Zhang, Li-Li Wu, Ping Bie, Feng Xia
BACKGROUND: Homeobox B7 (HOXB7) has been identified associated with poor prognosis of hepatocellular carcinoma (HCC). However, the specific mechanism by which HOXB7 promotes the malignant progression of HCC remains to be determined. METHODS: Immunohistochemistry (IHC) was used to detect the expression level of HOXB7 in 77-paired HCC tissue samples, and the correlation between HOXB7 and HCC prognosis was assessed. The location of HOXB7 was confirmed by immunofluorescence...
June 24, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28646304/ndrg2-knockdown-promotes-fibrosis-in-renal-tubular-epithelial-cells-through-tgf-%C3%AE-1-smad3-pathway
#16
Zhibo Jin, Chaohui Gu, Fengyan Tian, Zhankui Jia, Jinjian Yang
Renal fibrosis is a common pathological pathway of various chronic kidney diseases progressing to end-stage renal disease and is characterized by tubular atrophy, fibroblast/myofibroblast activation and excessive deposition of extracellular matrix (ECM). N-Myc downstream-regulated gene-2 (NDRG2) is reported to be associated with liver fibrosis in rats. However, the biological function of NDRG2 in renal fibrosis remains unclear. Therefore, we investigate the effect of NDRG2 on renal fibrosis and the underlying mechanism of NDRG2 in TGF-β1-induced renal tubular epithelial cells (HK-2)...
June 23, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28646117/cyclin-dependent-kinase-9-is-a-novel-specific-molecular-target-in-adult-t-cell-leukemia-lymphoma
#17
Tomoko Narita, Takashi Ishida, Asahi Ito, Ayako Masaki, Shiori Kinoshita, Susumu Suzuki, Hisashi Takino, Takashi Yoshida, Masaki Ri, Shigeru Kusumoto, Hirokazu Komatsu, Kazunori Imada, Yuetsu Tanaka, Takaori-Kondo Akifumi, Hiroshi Inagaki, Arne Scholz, Philip Lienau, Taruho Kuroda, Ryuzo Ueda, Shinsuke Iida
Cyclin-dependent kinase 9 (CDK9), a subunit of the positive transcription elongation factor b (P-TEFb) complex, regulates gene transcription elongation by phosphorylating the carboxy-terminal domain (CTD) of RNA polymerase II (RNAPII).  The deregulation of CDK9/P-TEFb has important implications for many cancer types.  BAY 1143572 is a novel and highly selective CDK9/P-TEFb inhibitor currently being investigated in phase I studies. We evaluated the therapeutic potential of BAY 1143572 in adult T-cell leukemia/lymphoma (ATL)...
June 23, 2017: Blood
https://www.readbyqxmd.com/read/28643779/drugging-the-undruggable-cancer-targets
#18
REVIEW
Chi V Dang, E Premkumar Reddy, Kevan M Shokat, Laura Soucek
The term 'undruggable' was coined to describe proteins that could not be targeted pharmacologically. However, progress is being made to 'drug' many of these targets, and therefore more appropriate terms might be 'difficult to drug' or 'yet to be drugged'. Many desirable targets in cancer fall into this category, including the RAS and MYC oncogenes, and pharmacologically targeting these intractable proteins is now a key challenge in cancer research that requires innovation and the development of new technologies...
June 23, 2017: Nature Reviews. Cancer
https://www.readbyqxmd.com/read/28643426/cell-of-origin-classification-by-gene-expression-and-myc-rearrangements-in-diffuse-large-b-cell-lymphoma-of-children-and-adolescents
#19
Monika Szczepanowski, Jonas Lange, Christian W Kohler, Neus Masque-Soler, Martin Zimmermann, Sietse M Aukema, Michael Altenbuchinger, Thorsten Rehberg, Friederike Mahn, Reiner Siebert, Rainer Spang, Birgit Burkhardt, Wolfram Klapper
We present the largest series of diffuse large B-cell lymphoma (DLBCL) in patients younger than 18 years analysed to date by gene expression profiling using Nanostring technology to identify molecular subtypes and fluorescent in situ hybridization for translocations of MYC. We show that the activated B cell-like subtype of DLBCL is exceedingly rare in children and - in contrast to adults- not associated with outcome. Furthermore, we review the current literature and demonstrate that MYC translocations are not more frequent in paediatric compared to adult DLBCL...
June 23, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28643330/muc1-c-is-a-target-in-lenalidomide-resistant-multiple-myeloma
#20
Li Yin, Ashujit Tagde, Reddy Gali, Yu-Tzu Tai, Teru Hideshima, Kenneth Anderson, David Avigan, Donald Kufe
Lenalidomide (LEN) acts directly on multiple myeloma (MM) cells by inducing cereblon-mediated degradation of interferon regulatory factor 4, Ikaros (IKZF)1 and IKZF3, transcription factors that are essential for MM cell survival. The mucin 1 (MUC1) C-terminal transmembrane subunit (MUC1-C) oncoprotein is aberrantly expressed by MM cells and protects against reactive oxygen species (ROS)-mediated MM cell death. The present studies demonstrate that targeting MUC1-C with GO-203, a cell-penetrating peptide inhibitor of MUC1-C homodimerization, is more than additive with LEN in downregulating the WNT/β-catenin pathway, suppressing MYC, and inducing late apoptosis/necrosis...
June 23, 2017: British Journal of Haematology
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