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https://www.readbyqxmd.com/read/28107698/the-natural-flavonoid-apigenin-sensitizes-human-cd44-prostate-cancer-stem-cells-to-cisplatin-therapy
#1
Suat Erdogan, Kader Turkekul, Rıza Serttas, Zeynep Erdogan
Prostate cancer (PCa) is the second most common type of cancer and the fifth leading cause of cancer-related death among men. Development of chemoresistance, tumor relapse and metastasis remain major barriers to effective treatment and all been identified to be associated with cancer stem cells (CSCs). Natural flavonoids such as apigenin have been shown to have the ability to improve the therapeutic efficacy of common chemotherapy agents through CSCs sensitization. Thus, the aim of this study was to evaluate the combination of apigenin with cisplatin on CD44(+) PCa stem cell growth and migration...
January 17, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28053959/sorbus-rufopilosa-extract-exhibits-antioxidant-and-anticancer-activities-by-inducing-cell-cycle-arrest-and-apoptosis-in-human-colon-adenocarcinoma-ht29-cells
#2
You Na Oh, Soojung Jin, Hyun-Jin Park, Hyun Ju Kwon, Byung Woo Kim
BACKGROUND: Sorbus rufopilosa, a tsema rowan, is a species of the small ornamental trees in the genus Sorbus and the family Rosaceae found in East Asia. The bioactivities of S. rufopilosa have not yet been fully determined. The objective of this study is to evaluate the antioxidant and anticancer effects of ethanol extract of S. rufopilosa (EESR) and to determine the molecular mechanism of its anticancer activity in human colon carcinoma HT29 cells. METHODS: To examine the antioxidant activity of EESR, 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity assay was performed...
December 2016: Journal of Cancer Prevention
https://www.readbyqxmd.com/read/28005359/cyclin-dependent-kinase-cdk-inhibitors-structure-activity-relationships-and-insights-into-the-cdk-2-selectivity-of-6-substituted-2-arylaminopurines
#3
Christopher R Coxon, Elizabeth Anscombe, Suzannah Jane Harnor, Mathew P Martin, Benoit Jean-Pierre Carbain, Bernard Thomas Golding, Ian Robert Hardcastle, Lisa K Harlow, Svitlana Korolchuk, Christopher J Matheson, David R Newell, Martin E M Noble, Mangaleswaran Sivaprakasam, Susan J Tudhope, David M Turner, Lan-Zhen Wang, Stephen R Wedge, Christopher Wong, Roger John Griffin, Jane A Endicott, Celine Cano
Purines and related heterocycles substituted at C-2 with 4'-sulfamoylanilino and at C-6 with a variety of groups have been synthesized with the aim of achieving selectivity of binding to CDK2 over CDK1. 6-Substituents that favour competitive inhibition at the ATP binding site of CDK2 were identified and typically exhibited 10-80-fold greater inhibition of CDK2 compared to CDK1. Most impressive was 4-((6-([1,1'-biphenyl]-3-yl)-9H-purin-2-yl)amino) benzenesulfonamide (73) that exhibited high potency towards CDK2 (IC50 0...
December 22, 2016: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27986745/dual-alk-and-cdk4-6-inhibition-demonstrates-on-target-synergy-against-neuroblastoma
#4
Andrew Wood, Kateryna Krytska, Hannah T Ryles, Nicole R Infarinato, Renata Sano, Theodore D Hansel, Lori S Hart, Frederick King, Timothy R Smith, Edward Ainscow, Kathryn B Grandinetti, Tove Tuntland, Sunkyu Kim, Giordano Caponigro, You-Qun He, Shiva Krupa, Nanxin Li, Jennifer Harris, Yael P Mosse
PURPOSE: Anaplastic Lymphoma Kinase (ALK) is the most frequently mutated oncogene in the pediatric cancer neuroblastoma. We performed an in vitro screen for synergistic drug combinations that target neuroblastomas with mutations in ALK to determine if drug combinations could enhance anti-tumor efficacy. EXPERIMENTAL DESIGN: We screened combinations of eight molecularly targeted agents against seventeen comprehensively characterized human neuroblastoma-derived cell lines...
December 16, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27977463/breast-cancer-updates-and-advances-in-2016
#5
Sara B Giordano, William Gradishar
PURPOSE OF REVIEW: Approximately 1 in 8 US women (12%) will develop invasive breast cancer over the course of her lifetime. In 2016, an estimated 246,660 new cases of invasive breast cancer are expected to be diagnosed and approximately 40,450 would die as a result of it. The global burden of breast cancer exceeds all other cancers and the incidence is increasing. The heterogeneity of breast cancer makes it a challenging solid tumor to diagnose and treat. This review focuses on the recent advances in breast cancer therapy including hormonal treatment of metastatic breast cancer, targeting cyclin-dependent kinases (CDK) 4/6 in breast cancer, updates in targeting human epidermal growth factor receptor 2 (HER2) positive breast cancer, adaptive randomization trial design and cancer genetic risk assessment...
February 2017: Current Opinion in Obstetrics & Gynecology
https://www.readbyqxmd.com/read/27750483/the-cdk-inhibitor-at7519m-in-patients-with-relapsed-or-refractory-chronic-lymphocytic-leukemia-cll-and-mantle-cell-lymphoma-a-phase-ii-study-of-the-canadian-cancer-trials-group
#6
Matthew D Seftel, John Kuruvilla, Tom Kouroukis, Versha Banerji, Graeme Fraser, Michael Crump, Rajat Kumar, Haji I Chalchal, Muhammad Salim, Rob C Laister, Susan Crocker, Spencer B Gibson, Marcia Toguchi, John F Lyons, Hao Xu, Jean Powers, Joana Sederias, Lesley Seymour, Annette E Hay
AT7519M is a small molecule inhibitor of cyclin-dependent kinases 1, 2, 4, 5, and 9 with in vitro activity against lymphoid malignancies. In two concurrent Phase II trials, we evaluated AT7519M in relapsed or refractory chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL) using the recommended Phase II dosing of 27 mg/m(2) twice weekly for 2 of every 3 weeks. Primary objective was objective response rate (ORR). Nineteen patients were accrued (7 CLL, 12 MCL). Four CLL patients achieved stable disease (SD)...
October 17, 2016: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/27671480/octyl-ester-of-ginsenoside-rh2-induces-apoptosis-and-g1-cell-cycle-arrest-in-human-hepg2-cells-by-activating-the-extrinsic-apoptotic-pathway-and-modulating-the-akt-p38-mapk-signaling-pathway
#7
Fang Chen, Shi-Lian Zheng, Jiang-Ning Hu, Yong Sun, Yue-Ming He, Han Peng, Bing Zhang, David Julian McClements, Ze-Yuan Deng
Ginsenoside Rh2 is a potential active metabolite of ginseng that has antitumor activity against a variety of tumor cells. Previously, we reported that Rh2-O, an octyl ester derivative of ginsenoside Rh2, had a higher anticancer activity than Rh2 through activating the intrinsic apoptotic pathway. In this study, we found that the extrinsic apoptotic pathway was also involved in Rh2-O-induced HepG2 cells apoptosis as evidenced by the up-regulation of Fas, FasL, TNFR1, and TNF-α as well as the cleavage of caspase 8...
October 3, 2016: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/27660267/activation-of-transient-receptor-potential-vanilloid-4-promotes-the-proliferation-of-stem-cells-in-the-adult-hippocampal-dentate-gyrus
#8
Yujing Tian, Mengwen Qi, Zhiwen Hong, Yingchun Li, Yibiao Yuan, Yimei Du, Lei Chen, Ling Chen
Neurogenesis plays an important role in adult hippocampal function, and this process can be modulated by intracellular calcium. The activation of transient receptor potential vanilloid 4 (TRPV4) induces an increase in intracellular calcium concentration, but whether neurogenesis can be modulated by TRPV4 activation remains unclear. Here, we report that intracerebroventricular injection of the TRPV4 agonist GSK1016790A for 5 days enhanced the proliferation of stem cells in the hippocampal dentate gyrus (DG) of adult mice without affecting neurite growth, differentiation, or survival of newborn cells...
September 22, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27649142/targeted-therapies-for-brain-metastases-from-breast-cancer
#9
REVIEW
Vyshak Alva Venur, José Pablo Leone
The discovery of various driver pathways and targeted small molecule agents/antibodies have revolutionized the management of metastatic breast cancer. Currently, the major targets of clinical utility in breast cancer include the human epidermal growth factor receptor 2 (HER2) and epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF) receptor, mechanistic target of rapamycin (mTOR) pathway, and the cyclin-dependent kinase 4/6 (CDK-4/6) pathway. Brain metastasis, however, remains a thorn in the flesh, leading to morbidity, neuro-cognitive decline, and interruptions in the management of systemic disease...
September 13, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27618020/downregulation-of-foxp1-inhibits-cell-proliferation-in-hepatocellular-carcinoma-by-inducing-g1-s-phase-cell-cycle-arrest
#10
Xin Wang, Ji Sun, Meiling Cui, Fangyu Zhao, Chao Ge, Taoyang Chen, Ming Yao, Jinjun Li
Forkhead box P1 (FOXP1) belongs to a family of winged-helix transcription factors that are involved in the processes of cellular proliferation, differentiation, metabolism, and longevity. FOXP1 can affect cell proliferation and migratory ability in hepatocellular carcinoma (HCC) in vitro. However, little is known about the mechanism of FOXP1 in the proliferation of HCC cells. This study aimed to further explore the function of FOXP1 on the proliferation of HCC cells as well as the relevant mechanism involved...
September 8, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27569395/antitumor-action-of-cdk-inhibitor-ls-007-as-a-single-agent-and-in-combination-with-abt-199-against-human-acute-leukemia-cells
#11
Shao Xie, Hui Jiang, Xiao-Wen Zhai, Fan Wei, Shu-Dong Wang, Jian Ding, Yi Chen
AIM: LS-007 is a CDK inhibitor, which exhibits potent antitumor activity against chronic lymphocytic leukemia and ovarian cancer cells. In this study, we further evaluated the antitumor activity of LS-007 alone and in combination with a Bcl-2 inhibitor ABT-199 in acute leukemia (AL) cells. METHODS: Cell viability was detected using resazurin assay, and cell apoptosis was examined using Annexin V/PI double staining and flow cytometry. The inhibition of LS-007 on kinases was evaluated with the mobility shift assay or ELISA...
November 2016: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/27565890/combination-screening-in-vitro-identifies-synergistically-acting-kp372-1-and-cytarabine-against-acute-myeloid-leukemia
#12
A Österroos, M Kashif, C Haglund, K Blom, M Höglund, C Andersson, M G Gustafsson, A Eriksson, R Larsson
Cytogenetic lesions often alter kinase signaling in acute myeloid leukemia (AML) and the addition of kinase inhibitors to the treatment arsenal is of interest. We have screened a kinase inhibitor library and performed combination testing to find promising drug-combinations for synergistic killing of AML cells. Cytotoxicity of 160 compounds in the library InhibitorSelect™ 384-Well Protein Kinase Inhibitor I was measured using the fluorometric microculture cytotoxicity assay (FMCA) in three AML cell lines. The 15 most potent substances were evaluated for dose-response...
October 15, 2016: Biochemical Pharmacology
https://www.readbyqxmd.com/read/27530044/-molecular-mechanisms-of-functional-activity-decreasing-of-the-skin-cells-with-its-aging
#13
REVIEW
V Kh Khavinson, N S Linkova, E O Kukanova, O A Orlova
The article discusses the pool of signaling molecules that regulate the functional activity of the skin cells. Molecules of apoptosis and cells skin aging are p53, p21, p15, Cdk 4/6 and Bcl-2. Inflammation in skin fibroblasts are realized through the cytokines TNF-α, TGF-β, IL-1, ICAM-1, matrix metalloproteinase MMP-1,2,3,9, transcription factor NF-κB and activator protein AP-1. An important role in the aging of skin cells play neuroimmunoendocrine signaling molecules--melatonin, serotonin, skin fibroblast proliferation marker chromogranin A and CD98hc...
April 2016: Uspekhi Fiziologicheskikh Nauk
https://www.readbyqxmd.com/read/27527160/1-2-hydroxy-5-methylphenyl-3-phenyl-1-3-propanedione-induces-g1-cell-cycle-arrest-and-autophagy-in-hela-cervical-cancer-cells
#14
Jie-Heng Tsai, Li-Sung Hsu, Hsiu-Chen Huang, Chih-Li Lin, Min-Hsiung Pan, Hui-Mei Hong, Wei-Jen Chen
The natural agent, 1-(2-hydroxy-5-methylphenyl)-3-phenyl-1,3-propanedione (HMDB), has been reported to have growth inhibitory effects on several human cancer cells. However, the role of HMDB in cervical cancer remains unclear. Herein, we found that HMDB dose- and time-dependently inhibited growth of HeLa cervical cancer cells, accompanied with G1 cell cycle arrest. HMDB decreased protein expression of cyclins D1/D3/E and cyclin-dependent kinases (CDKs) 2/4/6 and reciprocally increased mRNA and protein levels of CDK inhibitors (p15, p16, p21, and p27), thereby leading to the accumulation of hypophosphorylated retinoblastoma (Rb) protein...
August 5, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27496135/spectrum-and-degree-of-cdk-drug-interactions-predicts-clinical-performance
#15
Ping Chen, Nathan V Lee, Wenyue Hu, Meirong Xu, Rose Ann Ferre, Hieu Lam, Simon Bergqvist, James Solowiej, Wade Diehl, You-Ai He, Xiu Yu, Asako Nagata, Todd VanArsdale, Brion W Murray
Therapeutically targeting aberrant intracellular kinase signaling is attractive from a biological perspective but drug development is often hindered by toxicities and inadequate efficacy. Predicting drug behaviors using cellular and animal models is confounded by redundant kinase activities, a lack of unique substrates, and cell-specific signaling networks. Cyclin-dependent kinase (CDK) drugs exemplify this phenomenon because they are reported to target common processes yet have distinct clinical activities...
October 2016: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/27493616/palbociclib-first-cdk4-6-inhibitor-in-clinical-practice-for-the-treatment-of-advanced-hr-positive-breast-cancer
#16
REVIEW
Johannes Ettl
Palbociclib is the first inhibitor of the cyclin-dependent kinases (CDK) 4 and 6 to be introduced into clinical practice. Preclinical investigations led to its clinical development in advanced hormone receptor (HR)-positive breast cancer. To date, 2 significant clinical trials have been fully published. In this article, the results of these trials and their clinical relevance for the management of HR-positive advanced breast cancer are discussed.
June 2016: Breast Care
https://www.readbyqxmd.com/read/27493614/the-role-of-cdk-4-6-inhibitors-in-breast-cancer-treatment
#17
Isabell Witzel, Volkmar Müller
No abstract text is available yet for this article.
June 2016: Breast Care
https://www.readbyqxmd.com/read/27488531/an-in-vivo-reporter-to-quantitatively-and-temporally-analyze-the-effects-of-cdk4-6-inhibitor-based-therapies-in-melanoma
#18
Jessica L F Teh, Timothy J Purwin, Evan J Greenawalt, Inna Chervoneva, Allison Goldberg, Michael A Davies, Andrew E Aplin
Aberrant cell-cycle progression is a hallmark feature of cancer cells. Cyclin-dependent kinases 4 and 6 (CDK4/6) drive progression through the G1 stage of the cell cycle, at least in part, by inactivating the tumor suppressor, retinoblastoma. CDK4/6 are targetable and the selective CDK4/6 inhibitor, palbociclib, was recently FDA approved for the treatment of estrogen receptor-positive, HER2-negative advanced breast cancer. In cutaneous melanoma, driver mutations in NRAS and BRAF promote CDK4/6 activation, suggesting that inhibitors such as palbociclib are likely to provide therapeutic benefit in combination with BRAF inhibitors and/or MEK inhibitors that are FDA-approved...
September 15, 2016: Cancer Research
https://www.readbyqxmd.com/read/27428416/implications-of-genetic-and-epigenetic-alterations-of-cdkn2a-p16-ink4a-in-cancer
#19
REVIEW
Ran Zhao, Bu Young Choi, Mee-Hyun Lee, Ann M Bode, Zigang Dong
Aberrant gene silencing is highly associated with altered cell cycle regulation during carcinogenesis. In particular, silencing of the CDKN2A tumor suppressor gene, which encodes the p16(INK4a) protein, has a causal link with several different types of cancers. The p16(INK4a) protein plays an executional role in cell cycle and senescence through the regulation of the cyclin-dependent kinase (CDK) 4/6 and cyclin D complexes. Several genetic and epigenetic aberrations of CDKN2A lead to enhanced tumorigenesis and metastasis with recurrence of cancer and poor prognosis...
June 2016: EBioMedicine
https://www.readbyqxmd.com/read/27424288/nujiangexathone-a-a-novel-compound-from-garcinia-nujiangensis-suppresses-cervical-cancer-growth-by-targeting-hnrnpk
#20
Li Zhang, Jiling Feng, Siyuan Kong, Man Wu, Zhichao Xi, Baojun Zhang, Wenwei Fu, Yuanzhi Lao, Hongsheng Tan, Hongxi Xu
Cervical cancer is among the most frequently diagnosed cancers in females worldwide. Nujiangexathone A (NJXA), a novel compound from Garcinia nujiangensis, has been shown to have anti-cancer potential. In this study, the anti-tumor effects and the underlying mechanisms of NJXA action were investigated. Our results suggested that NJXA induced G0/G1 cell cycle arrest in HeLa and SiHa cells by down-regulating cyclins B1, E1, and A and cyclin-dependent kinases 2, 4 and 6, while selectively restoring p27. Using two-dimensional gel electrophoresis, we showed that NJXA reduced the expression of heterogeneous nuclear ribonucleoprotein K (hnRNPK) by accelerating ubiquitin-proteasome-dependent hnRNPK degradation, which then induced cell cycle arrest through the c-Myc-cyclin/Cdk-Rb-E2F1 pathway...
October 1, 2016: Cancer Letters
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