keyword
MENU ▼
Read by QxMD icon Read
search

Cdk4 inhibitor

keyword
https://www.readbyqxmd.com/read/27903987/mapping-heterogeneity-in-patient-derived-melanoma-cultures-by-single-cell-rna-seq
#1
Tobias Gerber, Edith Willscher, Henry Loeffler-Wirth, Lydia Hopp, Dirk Schadendorf, Manfred Schartl, Ulf Anderegg, Gray Camp, Barbara Treutlein, Hans Binder, Manfred Kunz
Recent technological advances in single-cell genomics make it possible to analyze cellular heterogeneity of tumor samples. Here, we applied single-cell RNA-seq to measure the transcriptomes of 307 single cells cultured from three biopsies of three different patients with a BRAF/NRAS wild type, BRAF mutant/NRAS wild type and BRAF wild type/NRAS mutant melanoma metastasis, respectively. Analysis based on self-organizing maps identified sub-populations defined by multiple gene expression modules involved in proliferation, oxidative phosphorylation, pigmentation and cellular stroma...
November 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/27903275/cell-cycle-inhibition-reduces-inflammatory-responses-neuronal-loss-and-cognitive-deficits-induced-by-hypobaria-exposure-following-traumatic-brain-injury
#2
Jacob W Skovira, Junfang Wu, Jessica J Matyas, Alok Kumar, Marie Hanscom, Shruti V Kabadi, Raymond Fang, Alan I Faden
BACKGROUND: Traumatic brain injury (TBI) patients in military settings can be exposed to prolonged periods of hypobaria (HB) during aeromedical evacuation. Hypobaric exposure, even with supplemental oxygen to prevent hypoxia, worsens outcome after experimental TBI, in part by increasing neuroinflammation. Cell cycle activation (CCA) after TBI has been implicated as a mechanism contributing to both post-traumatic cell death and neuroinflammation. Here, we examined whether hypobaric exposure in rats subjected to TBI increases CCA and microglial activation in the brain, as compared to TBI alone, and to evaluate the ability of a cyclin-dependent kinase (CDK) inhibitor (CR8) to reduce such changes and improve behavioral outcomes...
December 1, 2016: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/27899290/didymin-induces-apoptosis-through-mitochondrial-dysfunction-and-up-regulation-of-rkip-in-human-hepatoma-cells
#3
Jinbin Wei, Quanfang Huang, Facheng Bai, Jun Lin, Jinlan Nie, Shengjuan Lu, Chunyuang Lu, Renbin Huang, Zhongpeng Lu, Xing Lin
In the present study, a flavonoid was isolated from Origanum vulgare and identified as didymin. The effect and mechanism of O. vulgare didymin (OVD) on human HepG2 liver carcinoma cell was then assessed. Our results showed that OVD strongly inhibited the viability, clonogenicity and migration of HepG2 cells. OVD significantly induced apoptosis and induced cell cycle arrest at G2/M phase by regulating cyclin B1, cyclin D1 and CDK4. The anti-proliferative and pro-apoptotic effects were associated with changes in the Bcl-2/Bax ratio and induction of caspase-mediated apoptosis...
November 27, 2016: Chemico-biological Interactions
https://www.readbyqxmd.com/read/27883943/targeted-therapy-for-breast-cancer-and-molecular-mechanisms-of-resistance-to-treatment
#4
REVIEW
Guowei Gu, Derek Dustin, Suzanne Aw Fuqua
In recent years, clinical trials investigating new drugs and therapeutic combinations have led to promising advances in breast cancer therapy. Subtyping breast cancers into hormone receptor (HR) positive, epidermal growth factor receptor (HER2) positive, and triple negative breast cancer (TNBC) is currently the basis of diagnosing and treating this disease. In addition to endocrine and HER2-targeted therapies in their respective subtypes, evidence from recent preclinical studies have shown several targetable pathways that overcome resistance in the clinical setting...
November 21, 2016: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/27864574/enhancing-endocrine-therapy-combination-strategies-for-the-treatment-of-postmenopausal-hormone-receptor-positive-her2-advanced-breast-cancer
#5
REVIEW
Kathleen I Pritchard, Stephen K Chia, Christine Simmons, Deanna McLeod, Alexander Paterson, Louise Provencher, Daniel Rayson
: : Breast cancer (BC) is the most common malignancy in women worldwide, with approximately two-thirds having hormone receptor (HR)-positive tumors. New endocrine therapy (ET) strategies include combining ET agents as well as adding inhibitors targeting growth factors, angiogenesis, the mechanistic target of rapamycin, phosphoinositide 3-kinase (PI3K), or cyclin-dependent kinase 4/6 to ET. Level 1 evidence supports use of fulvestrant plus anastrozole or palbociclib plus letrozole as first-line therapy for HR-positive, HER2-negative advanced BC with special consideration for the former in ET-naïve patients, as well as everolimus plus exemestane or palbociclib plus fulvestrant as second-line therapy with special consideration in select first-line patients...
November 18, 2016: Oncologist
https://www.readbyqxmd.com/read/27864221/cyclin-d-mediates-tolerance-of-genome-doubling-in-cancers-with-functional-p53
#6
A Crockford, L P Zalmas, E Grönroos, S M Dewhurst, N McGranahan, M E Cuomo, V Encheva, A P Snijders, J Begum, S Purewal, J Cerveira, H Patel, M J Renshaw, C Swanton
BACKGROUND: Aneuploidy and chromosomal instability (CIN) are common features of human malignancy that fuel genetic heterogeneity. Although tolerance to tetraploidisation, an intermediate state that further exacerbates CIN, is frequently mediated by TP53 dysfunction, we find that some genome-doubled tumours retain wild-type TP53 We sought to understand how tetraploid cells with a functional p53/p21-axis tolerate genome-doubling events. METHODS: We performed quantitative proteomics in a diploid/tetraploid pair within a system of multiple independently-derived TP53 wild-type tetraploid clones arising spontaneously from a diploid progenitor...
November 17, 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/27849562/palbociclib-pd-0332991-a-selective-cdk4-6-inhibitor-restricts-tumour-growth-in-preclinical-models-of-hepatocellular-carcinoma
#7
Julien Bollard, Verónica Miguela, Marina Ruiz de Galarreta, Anu Venkatesh, C Billie Bian, Mark P Roberto, Victoria Tovar, Daniela Sia, Pedro Molina-Sánchez, Christie B Nguyen, Shigeki Nakagawa, Josep M Llovet, Yujin Hoshida, Amaia Lujambio
OBJECTIVE: Advanced hepatocellular carcinoma (HCC) is a lethal malignancy with limited treatment options. Palbociclib, a well-tolerated and selective CDK4/6 inhibitor, has shown promising results in the treatment of retinoblastoma (RB1)-positive breast cancer. RB1 is rarely mutated in HCC, suggesting that palbociclib could potentially be used for HCC therapy. Here, we provide a comprehensive characterisation of the efficacy of palbociclib in multiple preclinical models of HCC. DESIGN: The effects of palbociclib on cell proliferation, cellular senescence and cell death were investigated in a panel of human liver cancer cell lines, in ex vivo human HCC samples, in a genetically engineered mouse model of liver cancer, and in human HCC xenografts in vivo...
November 14, 2016: Gut
https://www.readbyqxmd.com/read/27849335/mycotoxin-verrucarin-a-inhibits-proliferation-and-induces-apoptosis-in-prostate-cancer-cells-by-inhibiting-prosurvival-akt-nf-kb-mtor-signaling
#8
Yongbo Liu, Xiaohua Gao, Dorrah Deeb, Yiguan Zhang, Jiajiu Shaw, Frederick A Valeriote, Subhash C Gautam
Trichothecenes are powerful mycotoxins that inhibit protein synthesis and induce ribotoxic stress response in mammalian cells. Verrucarin A (VC-A) is a Type D macrocyclic mycotoxin which inhibits cell proliferation and induces apoptosis in cancer cells. However, the antitumor activity of VC-A for prostate cancer cells has not been investigated. The objective of the present study was to determine the anticancer activity and its mechanism of action in hormone-responsive (LNCaP) and hormone-refractory (PC-3) carcinoma of the prostate (CaP) cell lines...
November 2016: Journal of Experimental Therapeutics & Oncology
https://www.readbyqxmd.com/read/27843622/review-of-hormone-based-treatments-in-postmenopausal-patients-with-advanced-breast-cancer-focusing-on-aromatase-inhibitors-and-fulvestrant
#9
REVIEW
Iben Kümler, Ann S Knoop, Christina A R Jessing, Bent Ejlertsen, Dorte L Nielsen
BACKGROUND: Endocrine therapy constitutes a central modality in the treatment of oestrogen receptor (ER)-positive advanced breast cancer. PURPOSE: To evaluate the evidence for endocrine treatment in postmenopausal patients with advanced breast cancer focusing on the aromatase inhibitors, letrozole, anastrozole, exemestane and fulvestrant. METHODS: A review was carried out using PubMed. Randomised phase II and III trials reporting on ≥100 patients were included...
2016: ESMO Open
https://www.readbyqxmd.com/read/27832204/expression-of-the-lncrna-maternally-expressed-gene-3-meg3-contributes-to-the-control-of-lung-cancer-cell-proliferation-by-the-rb-pathway
#10
Traci L Kruer, Susan M Dougherty, Lindsey Reynolds, Elizabeth Long, Tanya de Silva, William W Lockwood, Brian F Clem
Maternally expressed gene 3 (MEG3, mouse homolog Gtl2) encodes a long noncoding RNA (lncRNA) that is expressed in many normal tissues, but is suppressed in various cancer cell lines and tumors, suggesting it plays a functional role as a tumor suppressor. Hypermethylation has been shown to contribute to this loss of expression. We now demonstrate that MEG3 expression is regulated by the retinoblastoma protein (Rb) pathway and correlates with a change in cell proliferation. Microarray analysis of mouse embryonic fibroblasts (MEFs) isolated from mice with genetic deletion of all three Rb family members (TKO) revealed a significant silencing of Gtl2/MEG3 expression compared to WT MEFs, and re-expression of Gtl2/MEG3 caused decrease in cell proliferation and increased apoptosis...
2016: PloS One
https://www.readbyqxmd.com/read/27825114/pd-0332991-a-selective-cyclin-d-kinase-4-6-inhibitor-sensitizes-lung-cancer-cells-to-treatment-with-epidermal-growth-factor-receptor-tyrosine-kinase-inhibitors
#11
Minghui Liu, Song Xu, Yuli Wang, Ying Li, Yongwen Li, Hongbing Zhang, Hongyu Liu, Jun Chen
Acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) is a major challenge to targeted therapy for non-small cell lung cancer (NSCLC). We investigated whether a cyclin D kinase 4/6 (CDK4/6) inhibitor, PD 0332991, could reverse EGFR-TKI resistance in human lung cancer cells and explored the underlying mechanisms. We found that PD 0332991 potentiated gefitinib-induced growth inhibition in both EGFR-TKI-sensitive (PC-9) and EGFR-TKI-resistant (PC-9/AB2) cells by down-regulating proliferation and inducing apoptosis and G0/G1 cell cycle arrest...
November 4, 2016: Oncotarget
https://www.readbyqxmd.com/read/27822872/constitutive-expression-of-inducible-cyclic-adenosine-monophosphate-early-repressor-icer-in-cycling-quiescent-hematopoietic-cells-implications-for-aging-hematopoietic-stem-cells
#12
Steven J Greco, Ghassan Yehia, Julius A Potian, Carlos A Molina, Pranela Rameshwar
Despite extensive insights on the interaction between hematopoietic stem cells (HSCs) and the supporting bone marrow (BM) stroma in hematopoietic homeostasis there remains unanswered questions on HSC regulation. We report on the mechanism by which HSCs attain cycling quiescence by addressing a role for inducible cyclic AMP early repressor (ICER). ICER negatively transcriptional regulators of cAMP activators such as CREM and CREB. These activators can be induced by hematopoietic stimulators such as cytokines...
November 8, 2016: Stem Cell Reviews
https://www.readbyqxmd.com/read/27816766/fibroblast-growth-factor-9-fgf9-regulation-of-cyclin-d1-and-cyclin-dependent-kinase-4-in-ovarian-granulosa-and-theca-cells-of-cattle
#13
M L Totty, B C Morrell, L J Spicer
To determine the mechanism by which fibroblast growth factor 9 (FGF9) alters granulosa (GC) and theca (TC) cell proliferation, cell cycle proteins that regulate progression through G1 phase of the cell cycle, cyclin D1 (CCND1) and cyclin-dependent kinase-4 (CDK4; CCND1's catalytic partner), were evaluated. Ovaries were obtained from a local abattoir, GC were harvested from small (1-5 mm) and large (8-22 mm) follicles, and TC were harvested from large follicles. GC and TC were plated in medium containing 10% fetal calf serum followed by various treatments in serum-free medium...
November 3, 2016: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/27816545/effect-of-abemaciclib-ly2835219-on-enhancement-of-chemotherapeutic-agents-in-abcb1-and-abcg2-overexpressing-cells-in-vitro-and-in-vivo
#14
Tong Wu, Zhen Chen, Kenneth K W To, Xiaona Fang, Fang Wang, Bin Cheng, Liwu Fu
Multidrug resistance (MDR) is the major obstacle of the success in cancer chemotherapy. The overexpression of ATP-binding cassette (ABC) transporters, particularly ABCB1 and ABCG2, play a significant role in mediating MDR by pumping anticancer drugs out of cancer cells. Abemaciclib (LY2835219) is an orally bioavailable CDK4/6 inhibitor under phase III clinical trials. Here, we found that LY2835219 remarkably enhanced the efficacy of chemotherapeutic drugs in ABCB1 or ABCG2 over-expressing cancer cells in vitro and in vivo...
November 2, 2016: Biochemical Pharmacology
https://www.readbyqxmd.com/read/27811360/p16ink4a-suppresses-brca1-deficient-mammary-tumorigenesis
#15
Alexandria Scott, Feng Bai, Ho Lam Chan, Shiqin Liu, Jinshan Ma, Joyce M Slingerland, David J Robbins, Anthony J Capobianco, Xin-Hai Pei
Senescence prevents the proliferation of genomically damaged, but otherwise replication competent cells at risk of neoplastic transformation. p16INK4A (p16), an inhibitor of CDK4 and CDK6, plays a critical role in controlling cellular senescence in multiple organs. Functional inactivation of p16 by gene mutation and promoter methylation is frequently detected in human breast cancers. However, deleting p16 in mice or targeting DNA methylation within the murine p16 promoter does not result in mammary tumorigenesis...
November 2, 2016: Oncotarget
https://www.readbyqxmd.com/read/27810861/ribociclib-lengthens-breast-cancer-survival
#16
(no author information available yet)
The combination of antiestrogen therapy and ribociclib, an investigational CDK4/6 inhibitor, led to improved outcomes in women with metastatic HR-positive, HER2-negative breast cancer, according to findings presented at a meeting of the European Society for Medical Oncology. The combination significantly increased progression-free survival compared with letrozole alone in a large phase III trial-data that could lead to FDA approval.
November 3, 2016: Cancer Discovery
https://www.readbyqxmd.com/read/27796344/antileukemic-scalarane-sesterterpenoids-and-meroditerpenoid-from-carteriospongia-phyllospongia-sp-induce-apoptosis-via-dual-inhibitory-effects-on-topoisomerase-ii-and-hsp90
#17
Kuei-Hung Lai, Yi-Chang Liu, Jui-Hsin Su, Mohamed El-Shazly, Chih-Fung Wu, Ying-Chi Du, Yu-Ming Hsu, Juan-Cheng Yang, Ming-Kai Weng, Chia-Hua Chou, Guan-Yu Chen, Yu-Cheng Chen, Mei-Chin Lu
Two new scalarane sesterterpenoids, 12β-(3'β-hydroxybutanoyloxy)-20,24-dimethyl-24-oxo-scalara-16-en-25-al (1) and 12β-(3'β-hydroxypentanoyloxy)-20,24-dimethyl-24-oxo-scalara-16-en-25-al (2), along with one known tetraprenyltoluquinol-related metabolite (3), were isolated from the sponge Carteriospongia sp. In leukemia Molt 4 cells, 1 at 0.0625 μg/mL (125 nM) triggered mitochondrial membrane potential (MMP) disruption and apoptosis showing more potent effect than 2 and 3. The isolates inhibited topoisomerase IIα expression...
October 31, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27795451/3-deoxysappanchalcone-promotes-proliferation-of-human-hair-follicle-dermal-papilla-cells-and-hair-growth-in-c57bl-6-mice-by-modulating-wnt-%C3%AE-catenin-and-stat-signaling
#18
Young Eun Kim, Hyung Chul Choi, In-Chul Lee, Dong Yeon Yuk, Hyosung Lee, Bu Young Choi
3-Deoxysappanchalcone (3-DSC) has been reported to possess anti-allergic, antiviral, anti-inflammatory and antioxidant activities. In the present study, we investigated the effects of 3-DSC on the proliferation of human hair follicle dermal papilla cells (HDPCs) and mouse hair growth in vivo. A real-time cell analyzer system, luciferase assay, Western blot and real-time polymerase chain reaction (PCR) were employed to measure the biochemical changes occurring in HDPCs in response to 3-DSC treatment. The effect of 3-DSC on hair growth in C57BL/6 mice was also examined...
November 1, 2016: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/27785059/impact-of-palbociclib-combinations-on-treatment-of-advanced-estrogen-receptor-positive-human-epidermal-growth-factor-2-negative-breast-cancer
#19
REVIEW
Katalin Boér
Breast cancer is a heterogeneous disease with multiple subgroups based on clinical and molecular characteristics. For the largest subgroup of breast cancers, hormone receptor-positive/human epidermal growth factor 2 (HER2)-negative tumors, hormone treatment is the mainstay of therapy and is likely to result in significant improvement in disease outcomes. However, some of these cancers demonstrate de novo or acquired resistance to endocrine therapy. Despite intensive research to develop new strategies to enhance the efficacy of currently available treatment options for hormone receptor-positive breast cancer, progress has been slow, and there were few advances for a period of 10 years...
2016: OncoTargets and Therapy
https://www.readbyqxmd.com/read/27777309/her4-suppresses-p53-via-targeting-the-mdmx-mdm2-complex-implication-of-a-novel-mdmx-ser314-phosphosite
#20
Casimiro Gerarduzzi, Anna de Polo, Xue-Song Liu, Manale El Kharbili, John B Little, Zhi-Min Yuan
Deregulated receptor tyrosine kinase (RTK) signaling is frequently associated with tumorigenesis and therapy resistance, but its underlying mechanisms still need to be elucidated. In this study we have shown that the RTK human epidermal growth factor receptor 4 (Her4, aka Erbb4) can inhibit the tumor suppressor p53 by regulating the MDMX-MDM2 complex stabilization. Upon activation by either overexpression of a constitutively active vector or ligand binding (Neuregulin-1), Her4 was able to stabilize the MDMX-MDM2 complex resulting in suppression of p53 transcriptional activity, as shown by p53 responsive element-driven luciferase assay and mRNA levels of p53 target genes...
October 24, 2016: Journal of Biological Chemistry
keyword
keyword
1131
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"