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https://www.readbyqxmd.com/read/29344143/function-of-cell-cycle-regulators-in-predicting-silent-pituitary-adenoma-progression-following-surgical-resection
#1
Sung Hyun Park, Ji Hwan Jang, Young Min Lee, Joon Soo Kim, Kyu Hong Kim, Young Zoon Kim
The present study investigated the use of cell-cycle regulators for predicting the progression of silent pituitary adenoma (SPA) following surgical resection, via immunohistochemical analysis of tumor samples obtained by surgical resection. The medical records of patients diagnosed with SPA between January 2000 and December 2013 in the Samsung Changwon Hospital, Sungkyunkwan University School of Medicine (Changwon, South Korea) were reviewed. Immunohistochemical staining was performed on sections of the archived, paraffin-embedded tissues obtained by surgery, with all tissues stained for cell-cycle regulatory proteins p16, p15, p21, cyclin-dependent kinase (CDK)4, CDK6, retinoblastoma protein (pRb) and cyclin D1, as well as E3 ubiquitin-protein ligase mib1 (MIB-1) antigen and p53...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29318382/mir-29-silencing-modulates-the-expression-of-target-genes-related-to-proliferation-apoptosis-and-methylation-in-burkitt-lymphoma-cells
#2
Luciano Mazzoccoli, Marcela Cristina Robaina, Alexandre Gustavo Apa, Martin Bonamino, Luciana Wernersbach Pinto, Eduardo Queiroga, Carlos E Bacchi, Claudete Esteves Klumb
PURPOSE: Burkitt lymphoma (BL) is a B-cell lymphoma frequently diagnosed in children. It is characterized by MYC translocations, which lead to the constitutive expression of the MYC oncogene. MYC contributes to miR-29 repression through an E-box MYC binding site on the miR-29b-1/miR-29a promoter region. We evaluated the role of miR-29a/b/c and their predicted targets in BL pathogenesis. METHODS: Mature sequences of miR-29a/b/c were transfected to the BL cell lines BL41 and Raji, and evaluated for DNMT3B, MCL1, BIM, CDK6, AKT and TCL1 protein expression as well as for MCL-1 and CDK6 mRNA expression...
January 9, 2018: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/29290968/inhibition-of-ezh2-triggers-the-tumor-suppressive-mir-29b-network-in-multiple-myeloma
#3
Maria Angelica Stamato, Giada Juli, Enrica Romeo, Domenica Ronchetti, Mariamena Arbitrio, Daniele Caracciolo, Antonino Neri, Pierosandro Tagliaferri, Pierfrancesco Tassone, Nicola Amodio
Downregulation of tumor suppressor (TS) microRNAs (miRNAs) commonly occurs in human cancer, including multiple myeloma (MM). We previously demonstrated that miR-29b is a relevant TS miRNA, whose expression in MM cells is inhibited by HDAC4-dependent deacetylation. Here, we provide novel insights into epigenetic mechanisms suppressing miR-29b in MM. In MM patient-derived plasma cells, we found inverse correlation between miR-29b and EZH2 mRNA expression. Both siRNAs and pharmacologic inhibitors of EZH2 led to miR-29b upregulation, and this effect was ascribed to reduced H3K27-trimethylation (H3K27me3) of miR-29a/b-1 promoter regions...
December 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/29286103/gene-expression-profiling-of-acute-myeloid-leukemia-samples-from-adult-patients-with-aml-m1-and-m2-through-boutique-microarrays-real-time-pcr-and-droplet-digital-pcr
#4
Luiza Handschuh, Maciej Kaźmierczak, Marek C Milewski, Michał Góralski, Magdalena Łuczak, Marzena Wojtaszewska, Barbara Uszczyńska-Ratajczak, Krzysztof Lewandowski, Mieczysław Komarnicki, Marek Figlerowicz
Acute myeloid leukemia (AML) is the most common and severe form of acute leukemia diagnosed in adults. Owing to its heterogeneity, AML is divided into classes associated with different treatment outcomes and specific gene expression profiles. Based on previous studies on AML, in this study, we designed and generated an AML-array containing 900 oligonucleotide probes complementary to human genes implicated in hematopoietic cell differentiation and maturation, proliferation, apoptosis and leukemic transformation...
December 28, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29285312/rtl1-promotes-melanoma-proliferation-by-regulating-wnt-%C3%AE-catenin-signalling
#5
Guobiao Fan, Dan Ye, Songcheng Zhu, Jiajie Xi, Xudong Guo, Jing Qiao, Yukang Wu, Wenwen Jia, Guiying Wang, Guohuang Fan, Jiuhong Kang
Cutaneous melanoma is a highly malignant and metastatic skin cancer with high mortality. However, its underlying mechanisms remain largely unclear. Here, we found that retrotransposon-like 1 (RTL1) is highly enriched in melanoma tissue, especially in early and horizontal growth tissues. Knockdown of RTL1 in melanoma cells resulted in cell proliferation suppression; cell cycle arrest at G1 phase; and down-regulation of E2F1, CYCLIN D1, cyclin-dependent kinase 6 (CDK6) and c-MYC. Moreover, overexpression of RTL1 in melanoma cells accelerated cell proliferation, promoted passage of the cell cycle beyond G1 phase, and increased the expression of cell cycle related genes...
December 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/29285232/synergistic-effect-of-farnesyl-transferase-inhibitor-lonafarnib-combined-with-chemotherapeutic-agents-against-the-growth-of-hepatocellular-carcinoma-cells
#6
Jialiang Wang, Yifan Lian, Yurong Gu, Hongbo Wang, Lin Gu, Yanlin Huang, Liang Zhou, Yuehua Huang
Hepatocellular carcinoma (HCC) is a common and deadly cancer worldwide and is often refractory to chemotherapy due to the development of multidrug resistance. Lonafarnib is an orally active and potent non-peptidomimetic inhibitor of farnesyl transferase. Here, using in vitro HCC cell models, we demonstrated that lonafarnib inhibited tumor proliferation and reduced the activity of mitogen-activated protein kinases pathways. In addition, lonafarnib caused G1 to S phase arrest through the downregulation of Cyclin D1, CDK6 and SKP2, while it induced cellular apoptosis by promoting the cleavage and activation of Caspase-3 and PARP...
December 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/29283884/a-hypothesis-driven-approach-identifies-cdk4-and-cdk6-inhibitors-as-candidate-drugs-for-treatments-of-adrenocortical-carcinomas
#7
Djihad Hadjadj, Su-Jung Kim, Thomas Denecker, Laura Ben Driss, Jean-Charles Cadoret, Chrystelle Maric, Giuseppe Baldacci, Fabien Fauchereau
High proliferation rate and high mutation density are both indicators of poor prognosis in adrenocortical carcinomas. We performed a hypothesis-driven association study between clinical features in adrenocortical carcinomas and the expression levels of 136 genes involved in DNA metabolism and G1/S phase transition. In 79 samples downloaded from The Cancer Genome Atlas portal, high Cyclin Dependent Kinase 6 (CDK6) mRNA levels gave the most significant association with shorter time to relapse and poorer survival of patients...
December 26, 2017: Aging
https://www.readbyqxmd.com/read/29277177/-effect-of-circular-rna-ubap2-silencing-on-proliferation-and-invasion-of-human-lung-cancer-a549-cells-and-its-mechanism
#8
Yujing Yin, Hui Gao, Jia Guo, Yang Gao
BACKGROUND: It has been proven that circular RNAs (circRNAs) play an important role on the process of many types cancer and circUBAP2 was a cancer-promoting circRNA, however, the role and mechanism in lung cancer was not clear. The aim of this study is to investigate the effects of circUBAP2 on cell proliferation and invasion of human lung cancer A549 cells. METHODS: CCK-8 assay was employed to detect the effect of circUBAP2 sliencing on cell proliferation of A549 cells...
December 20, 2017: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
https://www.readbyqxmd.com/read/29247857/a-highly-potent-cdk4-6-inhibitor-was-rationally-designed-to-overcome-blood-brain-barrier-in-gliobastoma-therapy
#9
Lei Yin, Heng Li, Wenjian Liu, Zhenglin Yao, Zhenzhen Cheng, Huabei Zhang, Hui Zou
Glioblastoma multiforme (GBM) is the most common and deadliest of malignant brain tumors in adults. Disease development is associated with dysregulation of the cyclin D-CDK4/6-INK4-Rb pathway, resulting in increased proliferation; thus, CDK4/6 kinase inhibitors are promising candidates for GBM treatment. The recently developed CDK4/6 inhibitors, palbociclib, ribociclib, and abemaciclib, are effective in subcutaneous glioma models, but their blood-brain barrier (BBB) permeability is poor, limiting drug delivery to the central nervous system...
December 6, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29246317/shrimp-mir-34-from-shrimp-stress-response-to-virus-infection-suppresses-tumorigenesis-of-breast-cancer
#10
Yalei Cui, Xiaoyuan Yang, Xiaobo Zhang
During host stress response against virus infection, some animal microRNAs (miRNAs) can be upregulated to restore the virus-caused metabolic disorder of host cells via suppressing the expressions of miRNAs' target genes. These antiviral miRNAs may have antitumor capacity, because tumorigenesis results from metabolic disorder of cells. However, this subject has not been explored. In this study, the results showed that shrimp miR-34, which was upregulated during white spot syndrome virus (WSSV) infection, had antiviral activity in shrimp...
December 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/29244196/iron-overload-induces-g1-phase-arrest-and-autophagy-in-murine-preosteoblast-cells
#11
Wan-Jing Cen, Yi Feng, Shu-Shu Li, Wei-Liang Huang, Tao Zhang, Wu Zhang, Wei-Dong Kong, Jian-Wei Jiang
This study aimed to investigate the cell cycle arrest and autophagy induced by iron overload inMC3T3-E1 cells. MC3T3-E1 cells were cultured in different concentrations of ferric ammonium citrate (FAC), and Perls' Prussian blue reaction was used to detect the iron levels of the cells. CCK-8 assays were used to detect the growth of MC3T3-E1. The level of reactive oxygen species (ROS) within cells was investigated with DCFH-DA. PI staining was used to analyze the cell cycle distribution of MC3T3-E1 cells. Finally, the expression levels of cell cycle related proteins, autophagy related proteins, AKT, p38 MAPK, Stat3 and their downstream proteins were detected with western blot assays...
December 15, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29240787/brd3-4-inhibition-and-flt3-ligand-deprivation-target-pathways-that-are-essential-for-the-survival-of-human-mll-af9-leukemic-cells
#12
Marco Carretta, Annet Z Brouwers-Vos, Matthieu Bosman, Sarah J Horton, Joost H A Martens, Edo Vellenga, Jan Jacob Schuringa
In the present work we aimed to identify targetable signaling networks in human MLL-AF9 leukemias. We show that MLL-AF9 cells critically depend on FLT3-ligand induced pathways as well as on BRD3/4 for their survival. We evaluated the in vitro and in vivo efficacy of the BRD3/4 inhibitor I-BET151 in various human MLL-AF9 (primary) models and patient samples and analyzed the transcriptome changes following treatment. To further understand the mode of action of BRD3/4 inhibition, we performed ChIP-seq experiments on the MLL-AF9 complex in THP1 cells and compared it to RNA-seq data of I-BET151 treated cells...
2017: PloS One
https://www.readbyqxmd.com/read/29233926/targeting-cdk6-and-bcl2-exploits-the-myb-addiction-of-ph-acute-lymphoblastic-leukemia
#13
Marco De Dominici, Patrizia Porazzi, Angela Rachele Soliera, Samanta A Mariani, Sankar Addya, Paolo Fortina, Luke F Peterson, Orietta Spinelli, Alessandro Rambaldi, Giovanni Martinelli, Anna Ferrari, Ilaria Iacobucci, Bruno Calabretta
Philadelphia Chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) is currently treated with BCR-ABL1 tyrosine kinase inhibitors (TKI) in combination with chemotherapy. However, most patients develop resistance to TKI through BCR-ABL1-dependent and -independent mechanisms. Newly developed TKI can target Ph+ ALL cells with BCR-ABL1-dependent resistance; however, overcoming BCR-ABL1-independent mechanisms of resistance remains challenging because transcription factors (TF), which are difficult to inhibit, are often involved...
December 12, 2017: Cancer Research
https://www.readbyqxmd.com/read/29232585/synthesis-of-new-triterpenic-monomers-and-dimers-as-potential-antiproliferative-agents-and-their-molecular-docking-studies
#14
Aasim Saeed, Hidayat Hussain, Umair Shamraiz, Najeeb Ur Rehman, Husain Yar Khan, Amin Badshah, Lucie Heller, René Csuk, Majid Ali, Ajmal Khan, Ahmed Al-Harrasi
In the current investigation, new monomers of myrrhanone B and lupeolic acid were prepared via reaction of triterpenic acids with linkers in the presence of K2CO3. In addition, new bis-myrrhanone B homodimers, myrrhanone B-myrrhanol B heterodimers, and bis-myrrhanone β-boswellic acids heterodimer were prepared. Evaluation of these compounds on the proliferation of four different human cancer cell lines, viz., FaDu (pharynx carcinoma), A2780 (ovarian carcinoma), HT29 (colon adenocarcinoma) and A375 (malignant melanoma) has been performed...
December 9, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29232554/genomic-aberrations-that-activate-d-type-cyclins-are-associated-with-enhanced-sensitivity-to-the-cdk4-and-cdk6-inhibitor-abemaciclib
#15
Xueqian Gong, Lacey M Litchfield, Yue Webster, Li-Chun Chio, Swee Seong Wong, Trent R Stewart, Michele Dowless, Jack Dempsey, Yi Zeng, Raquel Torres, Karsten Boehnke, Cecilia Mur, Carlos Marugán, Carmen Baquero, Chunping Yu, Steven M Bray, Isabella H Wulur, Chen Bi, Shaoyou Chu, Hui-Rong Qian, Philip W Iversen, Farhana F Merzoug, Xiang S Ye, Christoph Reinhard, Alfonso De Dios, Jian Du, Charles W Caldwell, María José Lallena, Richard P Beckmann, Sean G Buchanan
Most cancers preserve functional retinoblastoma (Rb) and may, therefore, respond to inhibition of D-cyclin-dependent Rb kinases, CDK4 and CDK6. To date, CDK4/6 inhibitors have shown promising clinical activity in breast cancer and lymphomas, but it is not clear which additional Rb-positive cancers might benefit from these agents. No systematic survey to compare relative sensitivities across tumor types and define molecular determinants of response has been described. We report a subset of cancers highly sensitive to CDK4/6 inhibition and characterized by various genomic aberrations known to elevate D-cyclin levels and describe a recurrent CCND1 3'UTR mutation associated with increased expression in endometrial cancer...
December 11, 2017: Cancer Cell
https://www.readbyqxmd.com/read/29223555/emerging-roles-of-circular-rna-hsa_circ_0000064-in-the-proliferation-and-metastasis-of-lung-cancer
#16
Yan-Hong Luo, Xiang-Zhi Zhu, Ke-Wei Huang, Qian Zhang, Yan-Xin Fan, Peng-Wei Yan, Jing Wen
Circular RNAs (circRNAs), a novel class of widespread and diverse endogenous RNAs, can regulate gene expression in mammals. CircRNAs have recently been identified as microRNA sponges and involved in the development of some human diseases. However, the role of circRNAs in the process of tumorigenesis and development of lung cancer remains vague. The purpose of this study is to investigate the role of circRNAs in the lung cancer. In this study, we chose hsa_circ_0000064 as a targeted circRNA to investigate its clinical significances in lung cancer patients...
December 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29214525/treatment-of-melanoma-with-selected-inhibitors-of-signaling-kinases-effectively-reduces-proliferation-and-induces-expression-of-cell-cycle-inhibitors
#17
Dorota Ciołczyk-Wierzbicka, Dorota Gil, Piotr Laidler
Cancer treatment often tends to involve direct targeting enzymes essential for the growth and proliferation of cancer cells. The aim of this study was the recognition of the possible role of selected protein kinases: PI3K, ERK1/2, and mTOR in cell proliferation and cell cycle in malignant melanoma. We investigated the role of protein kinase inhibitors: U0126 (ERK1/2), LY294002 (PI3K), rapamycin (mTOR), everolimus (mTOR), GDC-0879 (B-RAF), and CHIR-99021 (GSK3beta) in cell proliferation and expression of crucial regulatory cell cycle proteins in human melanoma cells: WM793 (VGP) and Lu1205 (metastatic)...
December 6, 2017: Medical Oncology
https://www.readbyqxmd.com/read/29207676/circular-rna-hsa_circ_000984-promotes-colon-cancer-growth-and-metastasis-by-sponging-mir-106b
#18
Xiao-Wu Xu, Bo-An Zheng, Zhi-Ming Hu, Zhen-Yuan Qian, Chao-Jie Huang, Xi-Qiang Liu, Wei-Ding Wu
Circular RNAs (circRNAs) as a novel type of noncoding RNAs (ncRNAs) are widely studied in the development of human various diseases, including cancer. Here, we found circular RNA hsa_circ_000984 encoded by the CDK6 gene was remarkably upregulated in the tissues of colorectal cancer (CRC) patients and in the CRC cell lines. Moreover, high expression level of hsa_circ_000984 was significantly associated with advanced colorectal cancer. Further analysis revealed that hsa_circ_000984 knockdown could inhibit cell proliferation, migration, invasion in vitro and tumor formation in vivo in CRC cell lines...
October 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/29202464/hedgehog-signaling-drives-medulloblastoma-growth-via-cdk6
#19
David R Raleigh, Pervinder K Choksi, Alexis Leigh Krup, Wasima Mayer, Nicole Santos, Jeremy F Reiter
Medulloblastoma, an aggressive cancer of the cerebellum, is among the most common pediatric brain tumors. Approximately one-third of medulloblastomas are associated with misactivation of the Hedgehog (Hh) pathway. GLI family zinc finger 2 (GLI2) coordinates the Hh transcriptional program; however, the GLI2 targets that promote cancer cell proliferation are unknown. Here, we incorporated a Gli2-EGFP allele into 2 different genetic mouse models of Hh-associated medulloblastoma. Hh signaling induced GLI2 binding to the Cdk6 promoter and activated Cdk6 expression, thereby promoting uncontrolled cell proliferation...
November 20, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29185191/delivery-of-exogenous-mir-124-to-glioblastoma-multiform-cells-by-wharton-s-jelly-mesenchymal-stem-cells-decreases-cell-proliferation-and-migration-and-confers-chemosensitivity
#20
S Sharif, M H Ghahremani, M Soleimani
MicroRNAs (miRs) are potential therapeutic targets in glioblastoma multiforme (GBM), but the difficulties associated with their delivery to tumor target cells have hampered their widespread use. Mesenchymal stem cells (MSCs) can migrate to the sites of cancers, including GBM and exert anti-tumor effects. In this study, it is shown that Wharton's jelly-MSCs (WJ-MSCs) have the ability to deliver exogenous miRs to GBM cells and the functional impact of this delivery is characterized. It is found that the labeled miR-124, as an example for miR of interest, can be successfully delivered with WJ-MSCs to U87 GBM cells via dependent or exosome-independent processes...
November 28, 2017: Stem Cell Reviews
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