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https://www.readbyqxmd.com/read/28343074/cratoxy-formosum-leaf-extract-inhibits-proliferation-and-migration-of-human-breast-cancer-mcf-7-cells
#1
Benjaporn Buranrat, Nootchanat Mairuae, Ampa Konsue
In this study we investigated how Cratoxy formosum (CF) leaf extract affects the viability and migration of human breast cancer cells including the mechanism(s) responsible. Our results showed that CF leaf extract strongly induced MCF-7 cell death in a concentration- and time-dependent manner, with IC50 values of 85.70±4.52μg/mL and 53.74±3.02μg/mL at 24h and 48h, respectively. Additionally, CF leaf extract potentiated the activity of 4 anticancer drugs with the greatest synergy occurring between CF and 5-FU...
March 23, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28322158/effect-and-mechanism-of-curcumin-on-ezh2-mir-101-regulatory-feedback-loop-in-multiple-myeloma
#2
Chuanqing Wu, Tuo Ruan, Weizhen Liu, Xiaojie Zhu, Juan Pan, Wen Lu, Chen Yan, Kaixiong Tao, Weikang Zhang, Chun Zhang
BACKGROUND: Multiple myeloma is the second most prevalent hematologic malignancy and thought to be incurable. Therefore, it's urgent to find new drugs for treatment. Some experiments have shown that curcumin might have great potential in treating multiple myeloma, while the mechanism is still unknown. EZH2 and SUZ12 are the core proteins in PRC2 and their expression are increased in various human cancers, including the poor prognostic multiple myeloma. Meanwhile, the regulation of miRNAs and EZH2 has been demonstrated in other cancer researches, like lung cancer, pancreatic cancer, leukemia and so on...
March 17, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28318508/effects-of-novel-brominated-flame-retardant-tbph-and-its-metabolite-tbmehp-on-human-vascular-endothelial-cells-implication-for-human-health-risks
#3
Ping Xiang, Rong-Yan Liu, Hong-Jie Sun, Yun-Wen Yang, Xin-Yi Cui, Lena Q Ma
As a replacement for polybrominated diphenyl ethers, bis-(2-ethylhexyl) tetrabromophthalate (TBPH) is widely used as a novel flame retardant and has been detected in many environmental matrix including human blood. TBPH can be metabolized into mono-(2-ethyhexyl) tetrabromophthalate (TBMEHP) by carboxylesterase. However, their adverse effects on human vascular endothelium and their potential impacts on human cardiovascular disease are unknown. In this study, their adverse effects and associated molecular mechanisms on human vascular endothelial cells (HUVECs) were investigated...
March 16, 2017: Environmental Research
https://www.readbyqxmd.com/read/28286417/molecular-mechanism-of-g1-arrest-and-cellular-senescence-induced-by-lee011-a-novel-cdk4-cdk6-inhibitor-in-leukemia-cells
#4
Yan-Fang Tao, Na-Na Wang, Li-Xiao Xu, Zhi-Heng Li, Xiao-Lu Li, Yun-Yun Xu, Fang Fang, Mei Li, Guang-Hui Qian, Yan-Hong Li, Yi-Ping Li, Yi Wu, Jun-Li Ren, Wei-Wei Du, Jun Lu, Xing Feng, Jian Wang, Wei-Qi He, Shao-Yan Hu, Jian Pan
BACKGROUND: Overexpression of cyclin D1 dependent kinases 4 and 6 (CDK4/6) is a common feature of many human cancers including leukemia. LEE011 is a novel inhibitor of both CDK4 and 6. To date, the molecular function of LEE011 in leukemia remains unclear. METHODS: Leukemia cell growth and apoptosis following LEE011 treatment was assessed through CCK-8 and annexin V/propidium iodide staining assays. Cell senescence was assessed by β-galactosidase staining and p16(INK4a) expression analysis...
2017: Cancer Cell International
https://www.readbyqxmd.com/read/28283655/cell-cycle-regulation-accounts-for-variability-in-ki-67-expression-levels
#5
Michal Sobecki, Karim Mrouj, Jacques Colinge, François Gerbe, Philippe Jay, Liliana Krasinska, Vjekoslav Dulic, Daniel Fisher
The cell proliferation antigen Ki-67 is widely used in cancer histopathology, but estimations of Ki-67 expression levels are inconsistent and understanding of its regulation is limited. Here we show that cell cycle regulation underlies variable Ki-67 expression in all situations analyzed, including non-transformed human cells, normal mouse intestinal epithelia and adenomas, human cancer cell lines with or without drug treatments, and human breast and colon cancers. In normal cells, Ki-67 was a late marker of cell cycle entry; Ki-67 mRNA oscillated with highest levels in G2 while protein levels increased throughout the cell cycle, peaking in mitosis...
March 10, 2017: Cancer Research
https://www.readbyqxmd.com/read/28256614/mart-10-represses-cholangiocarcinoma-cell-growth-and-high-vitamin-d-receptor-expression-indicates-better-prognosis-for-cholangiocarcinoma
#6
Kun-Chun Chiang, Ta-Sen Yeh, Cheng-Cheng Huang, Yu-Chan Chang, Horng-Heng Juang, Chi-Tung Cheng, Jong-Hwei S Pang, Jun-Te Hsu, Masashi Takano, Tai C Chen, Atsushi Kittaka, Michael Hsiao, Chun-Nan Yeh
Cholangiocarcinoma (CCA) is a devastating disease due to no effective treatments available. Since the non-mineral functions of vitamin D emerges, 1α,25(OH)2D3, the active form of vitamin D, has been applied in anti-cancer researches. In this study, we demonstrated that both the 1α,25(OH)2D3 analog, MART-10, and 1α,25(OH)2D3 possessed anti-growth effect on human CCA cells with MART-10 much more potent than 1α,25(OH)2D3. The growth inhibition of both drugs were mediated by induction of G0/G1 cell cycle arrest through upregulation of p27 and downregulation of CDK4, CDK6, and cyclin D3...
March 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28255017/cdk6-contributes-to-cytoskeletal-stability-in-erythroid-cells
#7
Iris Z Uras, Ruth M Scheicher, Karoline Kollmann, Martin Glösmann, Michaela Prchal-Murphy, Anca S Tigan, Daniela A Fux, Sandro Altamura, Joana Neves, Martina Muckenthaler, Keiryn L Bennett, Stefan Kubicek, Philip W Hinds, Marieke von Lindern, Veronika Sexl
Mice lacking Cdk6 kinase activity suffer from mild anemia accompanied by elevated numbers of Ter119+ cells in the bone marrow. The animals show hardly any alterations in erythroid development, indicating that Cdk6 is not required for proliferation and maturation of erythroid cells. There is also no difference in stress erythropoiesis following hemolysis in vivo. However, Cdk6-/- erythrocytes have a shortened lifespan and are more sensitive to mechanical stress in vitro, suggesting differences in the cytoskeletal architecture...
March 2, 2017: Haematologica
https://www.readbyqxmd.com/read/28251887/yeats-domain-containing-4-promotes-gastric-cancer-cell-proliferation-and-mediates-tumor-progression-via-activating-the-wnt-%C3%AE-catenin-signaling-pathway
#8
Sheqing Ji, Youxiang Zhang, Binhai Yang
Increased expression of YEATS domain containing 4 (YEATS4) has been reported to have correlation with the progression in lots of cancers. However, the mechanism on how it promotes the development of gastric cancer (GC) is rarely reported. This study aimed to investigate the effect of YEATS4 on cell proliferation and tumor progression. The mRNA and protein expressions of YEATS4 in GC tissues and cell lines were analyzed. Then BGC-823 cells were overexpressed or silenced YEATS4 by transfection of different plasmids...
March 2, 2017: Oncology Research
https://www.readbyqxmd.com/read/28245384/-effects-of-tram-34-on-proliferation-and-invasion-of-leukemia-cell-line-hl-60
#9
Tian-Hua Jiang, Zhi-Gang Huang
OBJECTIVE: To investigate the effects of KCa3.1 channel inhibitor TRAM-34 on the proliferation and invasion of leukemia cell line HL-60. METHODS: HL-60 cells at logarithmic growth phase exposed to TRAM-34 at the final concentration of 25, 50, 75 and 100 nmol/L were used as experimental group. The HL-60 cells of control group was cultured in 10% fetal bovine serum-RPMI 1640. The proliferation inhibition rate of TRAM-34 on HL-60 cells was detected by adding MTT solution after 24, 48 and 72 h culture...
February 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28225893/lncrna-snhg12-promotes-cell-growth-and-inhibits-cell-apoptosis-in-colorectal-cancer-cells
#10
J Z Wang, C L Xu, H Wu, S J Shen
Several long non-coding RNA (lncRNA) might be correlated with the prognosis of colorectal cancer (CRC) and serve as a diagnostic and prognostic biomarker. However, the exact expression pattern of small nucleolar RNA host gene 12 (SNHG12) in colorectal cancer and its clinical significance remains unclear. The level of SNHG12 was detected by qRT-PCR in CRC tissues and CRC cells. MTT assay and colony formation assay were performed to examine the cell proliferation of CRC cells transfected with pcDNA-SNHG12 or si-SNHG12...
February 20, 2017: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
https://www.readbyqxmd.com/read/28214867/the-novel-long-noncoding-rna-tusc7-inhibits-proliferation-by-sponging-mir-211-in-colorectal-cancer
#11
Jian Xu, Rui Zhang, Jian Zhao
BACKGROUND/AIMS: The novel long noncoding RNA (lncRNA) tumor suppressor candidate 7 (TUSC7) has been reported as a potential tumor suppressor, while the functional role of TUSC7 is still unknown in colorectal cancer (CRC). Here, we characterized TUSC7 expression profile in CRC patients and investigated its biological function and potential molecular mechanism. METHODS: RNA isolation, qRT-PCR, cell counter kit-8 assay, cell cycle assay, EdU assay, and western blot were performed...
February 8, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28214639/congenital-glioblastoma-with-distinct-clinical-and-molecular-characteristics-case-reports-and-a-literature-review
#12
Masahiro Kameda, Yoshihiro Otani, Tomotsugu Ichikawa, Akira Shimada, Koichi Ichimura, Isao Date
BACKGROUND: The molecular diagnosis of brain tumors is important in classifying tumors and determining appropriate treatment. Congenital glioblastoma multiforme (GBM) is a rare tumor that occurs in infants, and the prognosis is poor. Approximately 60 patients diagnosed with congenital GBM have been reported. However, few reports have conducted molecular analyses of congenital GBM. CASE DESCRIPTION: We describe 2 congenital GBM patients treated in our hospital, and report results of immunohistochemistry, fluorescent in situ hybridization (FISH), direct sequencing, and methylation analyses...
February 16, 2017: World Neurosurgery
https://www.readbyqxmd.com/read/28193906/cbx3-promotes-colon-cancer-cell-proliferation-by-cdk6-kinase-independent-function-during-cell-cycle
#13
Yao Fan, Haiping Li, Xiaolong Liang, Zheng Xiang
Heterochromatin protein 1γ (CBX3) links histone methylation marks to transcriptional silence, DNA repair and RNA splicing, but a role for CBX3 in cancer remains largely unknown. In this study, we show that CBX3 in colon cancer cells promotes the progression of the cell cycle and proliferation in vitro and in vivo. Cell cycle (G1 phase to S phase) related gene CDK6 and p21 were further identified as targets of CBX3. In addition, we found that enhancing CDK6 suppresses cell proliferation by upregulating inhibitor p21 in the absence of CBX3, and this function is independent of the kinase activity of CDK6...
February 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28192398/cyclind-cdk4-6-complexes-phosphorylate-cdc25a-and-regulate-its-stability
#14
C Dozier, L Mazzolini, C Cénac, C Froment, O Burlet-Schiltz, A Besson, S Manenti
The phosphatase CDC25A is a key regulator of cell cycle progression by dephosphorylating and activating cyclin-CDK complexes. CDC25A is an unstable protein expressed from G1 until mitosis. CDC25A overexpression, which can be caused by stabilization of the protein, accelerates the G1/S and G2/M transitions, leading to genomic instability and promoting tumorigenesis. Thus, controlling CDC25A protein levels by regulating its stability is a critical mechanism for timing cell cycle progression and to maintain genomic integrity...
February 13, 2017: Oncogene
https://www.readbyqxmd.com/read/28171795/multifunctional-silver-nanocluster-hybrid-oligonucleotide-vehicle-for-cell-imaging-and-microrna-targeted-gene-silencing
#15
Hau-Yun Chen, Karunya Albert, Cheng-Che Wen, Pei-Ying Hsieh, Sih-Yu Chen, Nei-Chung Huang, Shen-Chuan Lo, Jen-Kun Chen, Hsin-Yun Hsu
Novel therapeutics is urgently needed to prevent cancer-related deaths. MicroRNAs that act as tumor suppressors have been recognized as a next-generation tumor therapy, and the restoration of tumor-suppressive microRNAs using microRNA replacements or mimics may be a less toxic, more effective strategy due to fewer off-target effects. Here, we designed the novel multifunctional oligonucleotide nanocarrier complex composed of a tumor-targeting aptamer sequence specific to mucin 1 (MUC1), poly-cytosine region for fluorescent silver nanocluster (AgNC) synthesis, and complimentary sequence for microRNA miR-34a loading...
April 1, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28168755/palbociclib-can-overcome-mutations-in-cyclin-dependent-kinase-6-that-break-hydrogen-bonds-between-the-drug-and-the-protein
#16
Stella Hernandez Maganhi, Patrizia Jensen, Ignez Caracelli, Julio Zukerman Schpector, Stefan Fröhling, Ran Friedman
Inhibition of cyclin dependent kinases (CDKs) 4 and 6 prevent cells from entering the synthesis phase of the cell cycle. CDK4 and 6 are therefore important drug targets in various cancers. The selective CDK4/6 inhibitor palbociclib is approved for the treatment of breast cancer and has shown activity in a cellular model of mixed lineage leukaemia (MLL)-rearranged acute myeloid leukaemia (AML). We studied the interactions of palbociclib and CDK6 using molecular dynamics simulations. Analysis of the simulations suggested several interactions that stabilised the drug in its binding site and that were not observed in the crystal structure of the protein-drug complex...
February 7, 2017: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/28156111/highly-potent-selective-and-orally-bioavailable-4-thiazol-n-pyridin-2-yl-pyrimidin-2-amine-cyclin-dependent-kinases-4-and-6-inhibitors-as-anticancer-drug-candidates-design-synthesis-and-evaluation
#17
Solomon Tadesse, Mingfeng Yu, Laychiluh B Mekonnen, Frankie Lam, Saiful Islam, Khamis Tomusange, Muhammed H Rahaman, Benjamin Noll, Sunita K C Basnet, Theodosia Teo, Hugo Albrecht, Robert Milne, Shudong Wang
Cyclin D dependent kinases (CDK4 and CDK6) regulate entry into S phase of the cell cycle and are validated targets for anticancer drug discovery. Herein we detail the discovery of a novel series of 4-thiazol-N-(pyridin-2-yl)pyrimidin-2-amine derivatives as highly potent and selective inhibitors of CDK4 and CDK6. Medicinal chemistry optimization resulted in 83, an orally bioavailable inhibitor molecule with remarkable selectivity. Repeated oral administration of 83 caused marked inhibition of tumor growth in MV4-11 acute myeloid leukemia mouse xenografts without having a negative effect on body weight and showing any sign of clinical toxicity...
February 16, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28151717/synergistic-drug-combinations-with-a-cdk4-6-inhibitor-in-t-cell-acute-lymphoblastic-leukemia
#18
Yana Pikman, Gabriela Alexe, Giovanni Roti, Amy Saur Conway, Andrew Furman, Emily S Lee, Andrew E Place, Sunkyu Kim, Chitra Saran, Rebecca Modiste, David M Weinstock, Marian Harris, Andrew L Kung, Lewis B Silverman, Kimberly Stegmaier
Purpose: Although significant progress has been made in the treatment of T-cell acute lymphoblastic leukemia (T-ALL), many patients will require additional therapy for relapsed/refractory disease. Cyclin D3 (CCND3) and CDK6 are highly expressed in T-ALL and have been effectively targeted in mutant NOTCH1-driven mouse models of this disease with a CDK4/6 small-molecule inhibitor. Combination therapy, however, will be needed for the successful treatment of human disease.Experimental Design: We performed preclinical drug testing using a panel of T-ALL cell lines first with LEE011, a CDK4/6 inhibitor, and next with the combination of LEE011 with a panel of drugs relevant to T-ALL treatment...
February 15, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28130125/histone-methyltransferase-setd2-is-critical-for-the-proliferation-and-differentiation-of-myoblasts
#19
Xin Yi, Ye Tao, Xi Lin, Yuan Dai, Tingli Yang, Xiaojing Yue, Xuejun Jiang, Xiaoyan Li, Ding-Sheng Jiang, Kelsey C Andrade, Jiang Chang
Skeletal muscle cell proliferation and differentiation are tightly regulated. Epigenetic regulation is a major component of the regulatory mechanism governing these processes. Histone modification is part of the epigenetic code used for transcriptional regulation of chromatin through the establishment of an active or repressive state for genes involved in myogenesis in a temporal manner. Here, we uncovered the function of SET domain containing 2 (Setd2), an essential histone 3 lysine 36 trimethyltransferase, in regulating the proliferation and differentiation of myoblasts...
April 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28129112/therapeutic-mir-21-silencing-ameliorates-diabetic-kidney-disease-in-mice
#20
Malte Kölling, Tamas Kaucsar, Celina Schauerte, Anika Hübner, Angela Dettling, Joon-Keun Park, Martin Busch, Xaver Wulff, Matthias Meier, Kristian Scherf, Nóra Bukosza, Gábor Szénási, Mária Godó, Amit Sharma, Michael Heuser, Peter Hamar, Claudia Bang, Hermann Haller, Thomas Thum, Johan M Lorenzen
Diabetic nephropathy is the main cause of end-stage renal disease. MicroRNAs are powerful regulators of the genome, and global expression profiling revealed miR-21 to be among the most highly regulated microRNAs in kidneys of mice with diabetic nephropathy. In kidney biopsies of diabetic patients, miR-21 correlated with tubulointerstitial injury. In situ PCR analysis showed a specific enrichment of miR-21 in glomerular cells. We identified cell division cycle 25a (Cdc25a) and cyclin-dependent kinase 6 (Cdk6) as novel miR-21 targets in mesangial cells...
January 4, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
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