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https://www.readbyqxmd.com/read/29156719/the-micrornas-mir-200b-3p-and-mir-429-5p-target-the-limk1-cfl1-pathway-to-inhibit-growth-and-motility-of-breast-cancer-cells
#1
Dengfeng Li, Hong Wang, Hongming Song, Hui Xu, Bingkun Zhao, Chenyang Wu, Jiashu Hu, Tianqi Wu, Dan Xie, Junyong Zhao, Qiang Shen, Lin Fang
Triple-negative breast cancer (TNBC) has the worst prognosis of all subtypes of breast cancer (BC), with limited options for conventional therapy and no targeted therapies. MicroRNAs (miRNAs) are small noncoding RNAs that negatively regulate gene expression. In this study, we aimed to determine whether two members of the miR-200 family, miR-200b-3p and miR-429-5p, are involved in BC cell proliferation and motility and to elucidate their target genes and pathways. We performed a meta-analysis that reveals down-regulated expression of miR-200b-3p and miR-429-5p in BC tissues and cell lines, consistent with a lower expression of miR-200b-3p and miR-429-5p in MDA-MB-231 and HCC1937 cells than in MCF-7 and MCF-10 cells...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29150788/ck4-ck6-cyclin-d1-p16-ink4a-and-egfr-expression-in-glioblastoma-with-a-primitive-neuronal-component
#2
Guiyan Xu, Jian Yi Li
Glioblastoma with primitive neuroectodermal tumor-like component (GBM-PNET) is a rare variant of glioblastoma, which was renamed as glioblastoma with a primitive neuronal component (GBM-PN) in new WHO classification of tumours of the central nervous system in 2016. There are few publications on the investigation of GBM-PN. In this study, PCR mRNA arrays on 6 cases of conventional GBM and 10 cases of GBM-PN showed high mRNA level of CDK4 in GBM-PN and low mRNA level of EGFR in GBM-PN. Immunohistochemical stains on tissue microarrays with 28 cases of conventional GBM and 13 cases of GBM-PN demonstrated that CDK4 was selectively expressed in the primitive neuronal component of all GBM-PN cases while EGFR was positive in conventional GBM and glial component of GBM-PN, but was negative in the primitive neuronal component of all GBM-PN cases...
November 17, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29149451/transcriptional-alterations-in-hereditary-and-sporadic-nonfunctioning-pancreatic-neuroendocrine-tumors-according-to-genotype
#3
Xavier M Keutgen, Suresh Kumar, Sudheer Gara, Myriem Boufraqech, Sunita Agarwal, Ralph H Hruban, Naris Nilubol, Martha Quezado, Richard Finney, Maggie Cam, Electron Kebebew
BACKGROUND: Nonfunctioning pancreatic neuroendocrine tumors (NFPanNETs) may be sporadic or inherited because of germline mutations associated with von Hippel-Lindau disease (VHL) or multiple endocrine neoplasia type 1 (MEN1). The clinical behavior of NFPanNETs is difficult to predict, even in tumors of the same stage and grade. The authors analyzed genotype-specific patterns of transcriptional messenger RNA (mRNA) levels of NFPanNETs to understand the molecular features that determine PanNET phenotype...
November 17, 2017: Cancer
https://www.readbyqxmd.com/read/29137335/inhibition-of-cell-cycle-progression-by-the-hydroxytyrosol-cetuximab-combination-yields-enhanced-chemotherapeutic-efficacy-in-colon-cancer-cells
#4
Erika Terzuoli, Ginevra Nannelli, Maria Frosini, Antonio Giachetti, Marina Ziche, Sandra Donnini
Hydroxytyrosol (HT), a polyphenol of olive oil, downregulates epidermal growth factor (EGFR) expression and inhibits cell proliferation in colon cancer (CC) cells, with mechanisms similar to that activated by the EGFR inhibitor, cetuximab. Here, we studied whether HT treatment would enhance the cetuximab inhibitory effects on cell growth in CC cells. HT-cetuximab combination showed greater efficacy in reducing cell growth in HT-29 and WiDr cells at concentrations 10 times lower than when used as single agents...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29117881/downregulated-trophinin-associated-protein-plays-a-critical-role-in-human-hepatocellular-carcinoma-through-upregulation-of-tumor-cell-growth-and-migration
#5
Yifan Lian, Weiming Fan, Yanlin Huang, Hongbo Wang, Jialiang Wang, Liang Zhou, Xiaojuan Wu, Meihai Deng, Yuehua Huang
Trophinin Associated Protein (TROAP) was a protein first identified to mediate the process of embryo transplantation and later found to be involved in microtubule regulation. However, little is known about the role of TROAP in hepatocellular carcinoma (HCC). In the present study, we reported that both TROAP mRNA and protein expressions were downregulated in human HCC samples as well as cell lines. High level of TROAP was associated with small tumor size (P < 0.05), minor tumor nodules (P < 0.01) and mild vein invasion (P < 0...
November 8, 2017: Oncology Research
https://www.readbyqxmd.com/read/29113274/simvastatin-potentiates-doxorubicin-activity-against-mcf-7-breast-cancer-cells
#6
Benjaporn Buranrat, Wanwisa Suwannaloet, Jarinyaporn Naowaboot
Simvastatin is a low density lipoprotein-lowering drug that is widely used to prevent and treat cardiovascular disease by inhibiting the mevalonate pathway. Simvastatin also exhibits inhibitory effects on a number of types of cancer. In the present study, the effects of simvastatin on the activity of doxorubicin in the breast cancer MCF-7 cell line, and the mechanisms by which this interaction occurs were investigated. The effect of simvastatin and doxorubicin treatment, alone and in combination, on the growth of MCF-7 cells was evaluated by a sulforhodamine B and colony formation assay...
November 2017: Oncology Letters
https://www.readbyqxmd.com/read/29109039/piperlongumine-decreases-cell-proliferation-and-the-expression-of-cell-cycle-associated-proteins-by-inhibiting-akt-pathway-in-human-lung-cancer-cells
#7
Jin Sil Seok, Chang Hee Jeong, Michael C Petriello, Han Geuk Seo, Hyunjin Yoo, Kwonho Hong, Sung Gu Han
Piperlongumine (PL) is an alkaloid of a pepper plant found in Southeast Asia. PL is known to induce selective toxicity towards a variety of cancer cell types. To explore the possible anti-lung cancer effects of PL, A549 cells were treated with PL (0-40 μM) for 24 h. Alterations in the expression of cell cycle-associated proteins (cyclin D1, cyclin-dependent kinase 4 (CDK4), CDK6 and retinoblastoma (Rb)) and intracellular signaling molecules (extracellular signal receptor-activated kinase 1/2 (ERK1/2), Akt, p38 and nuclear factor-κB (NF-κB)) were examined in cells following treatment of PL using Western blot analysis...
November 6, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/29108955/reduced-state-transition-barrier-of-cdk6-from-open-to-closed-state-induced-by-thr177-phosphorylation-and-its-implication-in-binding-modes-of-inhibitors
#8
Huan He, Juan Xu, Wen Xie, Qing-Lian Guo, Feng-Lei Jiang, Yi Liu
BACKGROUND: CDK6 is considered as a highly validated anticancer drug target due to its essential role in regulating cell cycle progression at G1 restriction point. Activation of CDK6 requires the phosphorylation of Thr177 on A-loop, but the structural insights of the activation mechanism remain unclear. METHODS: Herein, all-atoms molecular dynamics (MD) simulations were used to study the effects of Thr177 phosphorylation on the dynamic structure of CDK6-Vcyclin complex...
November 3, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29106415/evolution-and-clinical-impact-of-co-occurring-genetic-alterations-in-advanced-stage-egfr-mutant-lung-cancers
#9
Collin M Blakely, Thomas B K Watkins, Wei Wu, Beatrice Gini, Jacob J Chabon, Caroline E McCoach, Nicholas McGranahan, Gareth A Wilson, Nicolai J Birkbak, Victor R Olivas, Julia Rotow, Ashley Maynard, Victoria Wang, Matthew A Gubens, Kimberly C Banks, Richard B Lanman, Aleah F Caulin, John St John, Anibal R Cordero, Petros Giannikopoulos, Andrew D Simmons, Philip C Mack, David R Gandara, Hatim Husain, Robert C Doebele, Jonathan W Riess, Maximilian Diehn, Charles Swanton, Trever G Bivona
A widespread approach to modern cancer therapy is to identify a single oncogenic driver gene and target its mutant-protein product (for example, EGFR-inhibitor treatment in EGFR-mutant lung cancers). However, genetically driven resistance to targeted therapy limits patient survival. Through genomic analysis of 1,122 EGFR-mutant lung cancer cell-free DNA samples and whole-exome analysis of seven longitudinally collected tumor samples from a patient with EGFR-mutant lung cancer, we identified critical co-occurring oncogenic events present in most advanced-stage EGFR-mutant lung cancers...
November 6, 2017: Nature Genetics
https://www.readbyqxmd.com/read/29104466/the-crosstalk-between-hdpscs-and-hucmscs-on-proliferation-and-osteogenic-genes-expression-in-coculture-system
#10
Linglu Jia, Weiting Gu, Yunpeng Zhang, Yawen Ji, Jin Liang, Yong Wen, Xin Xu
Objectives: The present study established a non-contact coculture system in vitro, aiming to investigate the crosstalk between human dental pulp stem cells (hDPSCs) and human umbilical cord mesenchymal stem cells (hUCMSCs) on proliferation activity and osteogenic genes expression through paracrine. Materials and methods: The stemness of hDPSCs and hUCMSCs were identified by flow cytometric analysis and multipotential differentiation assays. With the help of transwell inserts, the non-contact coculture system in vitro was established between hDPSCs and hUCMSCs...
2017: International Journal of Medical Sciences
https://www.readbyqxmd.com/read/29103955/cell-cycle-proteins-control-production-of-neutrophil-extracellular-traps
#11
Borko Amulic, Sebastian Lorenz Knackstedt, Ulrike Abu Abed, Nikolaus Deigendesch, Christopher J Harbort, Brian E Caffrey, Volker Brinkmann, Frank L Heppner, Philip W Hinds, Arturo Zychlinsky
Neutrophils are essential for immune defense and can respond to infection by releasing chromatin in the form of neutrophil extracellular traps (NETs). Here we show that NETs are induced by mitogens and accompanied by induction of cell-cycle markers, including phosphorylation of the retinoblastoma protein and lamins, nuclear envelope breakdown, and duplication of centrosomes. We identify cyclin-dependent kinases 4 and 6 (CDK4/6) as essential regulators of NETs and show that the response is inhibited by the cell-cycle inhibitor p21(Cip)...
November 20, 2017: Developmental Cell
https://www.readbyqxmd.com/read/29097609/recent-advances-of-cell-cycle-inhibitor-therapies-for-pediatric-cancer
#12
REVIEW
Christopher C Mills, E A Kolb, Valerie B Sampson
This review describes the pivotal roles of cell-cycle and checkpoint regulators and discusses development of specific cell-cycle inhibitors for therapeutic use for pediatric cancer. The mechanism of action as well as the safety and tolerability of drugs in pediatric patients, including compounds that target CDK4/CDK6 (palbociclib, ribociclib, and abemaciclib), aurora kinases (AT9283 and MLN8237), Wee1 kinase (MK-1775), KSP (ispinesib), and tubulin (taxanes, vinca alkaloids), are presented. The design of mechanism-based combinations that exploit the cross-talk of signals activated by cell-cycle arrest, as well as pediatric-focused drug development, are critical for the advancement of drugs for rare childhood diseases...
November 2, 2017: Cancer Research
https://www.readbyqxmd.com/read/29095844/ensemble-based-modeling-and-rigidity-decomposition-of-allosteric-interaction-networks-and-communication-pathways-in-cyclin-dependent-kinases-differentiating-kinase-clients-of-the-hsp90-cdc37-chaperone
#13
Gabrielle Stetz, Amanda Tse, Gennady M Verkhivker
The overarching goal of delineating molecular principles underlying differentiation of protein kinase clients and chaperone-based modulation of kinase activity is fundamental to understanding activity of many oncogenic kinases that require chaperoning of Hsp70 and Hsp90 systems to attain a functionally competent active form. Despite structural similarities and common activation mechanisms shared by cyclin-dependent kinase (CDK) proteins, members of this family can exhibit vastly different chaperone preferences...
2017: PloS One
https://www.readbyqxmd.com/read/29091774/differential-regulation-of-g1-cdk-complexes-by-the-hsp90-cdc37-chaperone-system
#14
Stephen T Hallett, Martyna W Pastok, R Marc L Morgan, Anita Wittner, Katie L I M Blundell, Ildiko Felletar, Stephen R Wedge, Chrisostomos Prodromou, Martin E M Noble, Laurence H Pearl, Jane A Endicott
Selective recruitment of protein kinases to the Hsp90 system is mediated by the adaptor co-chaperone Cdc37. We show that assembly of CDK4 and CDK6 into protein complexes is differentially regulated by the Cdc37-Hsp90 system. Like other Hsp90 kinase clients, binding of CDK4/6 to Cdc37 is blocked by ATP-competitive inhibitors. Cdc37-Hsp90 relinquishes CDK6 to D3- and virus-type cyclins and to INK family CDK inhibitors, whereas CDK4 is relinquished to INKs but less readily to cyclins. p21CIP1 and p27KIP1 CDK inhibitors are less potent than the INKs at displacing CDK4 and CDK6 from Cdc37...
October 31, 2017: Cell Reports
https://www.readbyqxmd.com/read/29078212/-current-status-of-targeted-treatment-in-breast-cancer
#15
Katharina Seiffert, Barbara Schmalfeldt, Volkmar Müller
Within the last years, significant improvements have been achieved in breast cancer treatment, particularly with the development of targeted therapies. Major progress has been made in identifying the drivers malignant growth in oestrogen-receptor-positive breast cancer and the mechanisms of resistance to endocrine therapy. This progress has translated into several targeted therapies that enhance the efficacy of endocrine therapy; inhibitors of the cyclin-dependent kinases CDK4 and CDK6 like palbociclib and inhibitors of mTOR substantially improve progression-free survival...
November 2017: Deutsche Medizinische Wochenschrift
https://www.readbyqxmd.com/read/29075786/angiotensin-receptor-blocker-telmisartan-inhibits-cell-proliferation-and-tumor-growth-of-cholangiocarcinoma-through-cell-cycle-arrest
#16
Eri Samukawa, Shintaro Fujihara, Kyoko Oura, Hisakazu Iwama, Yoshimi Yamana, Tomoko Tadokoro, Taiga Chiyo, Kiyoyuki Kobayashi, Asahiro Morishita, Mai Nakahara, Hideki Kobara, Hirohito Mori, Keiichi Okano, Yasuyuki Suzuki, Takashi Himoto, Tsutomu Masaki
Cholangiocarcinoma (CCA) is at an advanced stage at the time of its diagnosis, and developing a more effective treatment of CCA would be desirable. Angiotensin II type 1 (AT1) receptor blocker (ARB), telmisartan may inhibit cancer cell proliferation, but the mechanisms by which telmisartan affects various cancers remain unknown. In this study, we evaluated the effects of telmisartan on human CCA cells and to assess the expression of microRNAs (miRNAs). We studied the effects of telmisartan on CCA cells using two cell lines, HuCCT-1 and TFK-1...
December 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29073835/mir-9-induces-cell-arrest-and-apoptosis-of-oral-squamous-cell-carcinoma-via-cdk-4-6-pathway
#17
Anquan Shang, Wen-Ying Lu, Man Yang, Cheng Zhou, Hong Zhang, Zheng-Xin Cai, Wei-Wei Wang, Wan-Xiang Wang, Gui-Qi Wu
Oral cancer remains a major public concern with considerable socioeconomic impact in the world, especially in southeast Asia. Despite substantial advancements have been made in treating oral cancer, the five-year survival rate for OSCC remained undesirable, and 35-55% patients developed recurrence within two years even with multimodality therapeutic strategies. Hence, identification of novel biomarkers for diagnosis and evaluating clinical outcome is of vital importance. MicroRNAs are 22-24 nt non-coding RNAs that could bind to 3' UTR of target mRNAs, thereby inducing degradation of mRNA or inhibiting translation...
October 26, 2017: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/29073265/mirna-124-is-a-link-between-measles-virus-persistent-infection-and-cell-division-of-human-neuroblastoma-cells
#18
Hila Naaman, Glenn Rall, Christine Matullo, Isana Veksler-Lublinsky, Yonat Shemer-Avni, Jacob Gopas
Measles virus (MV) infects a variety of lymphoid and non-lymphoid peripheral organs. However, in rare cases, the virus can persistently infect cells within the central nervous system. Although some of the factors that allow MV to persist are known, the contribution of host cell-encoded microRNAs (miRNA) have not been described. MiRNAs are a class of noncoding RNAs transcribed from genomes of all multicellular organisms and some viruses, which regulate gene expression in a sequence-specific manner. We have studied the contribution of host cell-encoded miRNAs to the establishment of MV persistent infection in human neuroblastoma cells...
2017: PloS One
https://www.readbyqxmd.com/read/29072058/p16ink4a-expression-in-cervical-lesions-correlates-with-histologic-grading-a-tertiary-level-medical-facility-based-retrospective-study
#19
Usha Sarma, Ira Biswas, Alakananda Das, Gokul Chandra Das, Chandan Saikia, Bidula Sarma
p16INK4a is a tumor-suppressor protein and cyclin-dependent kinase (cdk) inhibitor that blocks cdk4- and cdk6-mediated pRb phosphorylation to inhibit E2F-dependent transcription and cell-cycle progression. Because the E7 protein of high-risk HPVs inactivates pRB, the resulting overexpression of p16INK4a may be a good marker for infection with high risk HPV types. Immunostaining of p16INK4a allows precise identification of even small CIN or cervical cancer lesions in biopsy sections and can help reduce inter-observer variation in the histopathological interpretation of cervical biopsy specimens...
October 26, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/29061795/berberine-and-evodiamine-act-synergistically-against-human-breast-cancer-mcf-7-cells-by-inducing-cell-cycle-arrest-and-apoptosis
#20
Jia Du, Yang Sun, Yi-Yu Lu, Eric Lau, Ming Zhao, Qian-Mei Zhou, Shi-Bing Su
BACKGROUND/AIM: The synergistic combinations of natural products have long been the basis of Traditional Chinese herbal Medicine formulas. In this study, we investigated the synergistic effects of a combination of berberine and evodiamine against human breast cancer MCF-7 cells in vitro and in vivo, and explored its mechanism. MATERIALS AND METHODS: Cell survival was measured using the MTT assay. Apoptosis-related proteins were observed using western blot analysis...
November 2017: Anticancer Research
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