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https://www.readbyqxmd.com/read/29777701/ropivacaine-inhibits-the-migration-of-esophageal-cancer-cells-via-sodium-channel-independent-but-prenylation-dependent-inhibition-of-rac1-jnk-paxillin-fak
#1
Yaqin Zhang, Xiaohong Peng, Qinghong Zheng
The direct anti-proliferative and pro-apoptotic effects of local anesthetics have been well documented in various cancers. However, whether local anesthetics affect cancer metastasis and their underlying molecular mechanisms are not well understood. In this work, we show that ropivacaine at the clinically relevant concentration significantly inhibits esophageal cancer cell migration. Interestingly, ropivacaine at the same concentration does not display inhibitory effects on esophageal cancer cell growth and survival...
May 16, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29775995/phosphorylation-alters-bim-mediated-mcl-1-stabilization-and-priming
#2
Jason E Conage-Pough, Lawrence H Boise
Mcl-1 is a highly labile protein, subject to extensive posttranslational regulation. This distinguishes Mcl-1 from other anti-apoptotic proteins and necessitates further study to better understand how interactions with pro-apoptotic Bcl-2 proteins affect its regulation. One such protein, Bim, is known to stabilize Mcl-1, and Bim phosphorylation has been associated with increased Mcl-1 binding. Consequently, we investigated the potential impact of Bim phosphorylation on Mcl-1 stability. We found that Bim stabilizes and primes Mcl-1 in RPCI-WM1 cells and is constitutively phosphorylated...
May 18, 2018: FEBS Journal
https://www.readbyqxmd.com/read/29774773/mir-711-induced-down-regulation-of-angiopoietin-1-mediates-neuronal-cell-death
#3
Boris Sabirzhanov, Alan Faden, Taryn Aubrecht, Rebecca Henry, Ethan Glaser, Bogdan A Stoica
Angiopoietin-1 (Ang-1) is a well-known endothelial growth factor but its effects on neurons have yet to be elucidated. We show that Ang-1 is rapidly down-regulated in the injured brain after controlled cortical impact (CCI), a mouse experimental TBI model and in etoposide-induced neuronal apoptosis in vitro. Ang-1 treatment inhibits etoposide-induced up-regulation of pro-apoptotic Bcl-2 family members Noxa, Puma, Bim, and Bax; reduces markers of caspase-dependent (cytochrome c release/caspase activation) and caspase-independent (apoptosis-inducing factor release) pathways; and limits neuronal cell death...
May 18, 2018: Journal of Neurotrauma
https://www.readbyqxmd.com/read/29774113/ezh2-inhibitors-sensitize-myeloma-cell-lines-to-panobinostat-resulting-in-unique-combinatorial-transcriptomic-changes
#4
Taylor Harding, Jessica Swanson, Brian Van Ness
Multiple myeloma (MM) remains a largely incurable hematologic cancer due to an inability to broadly target inevitable drug-resistant relapse. Epigenetic abnormalities are abundantly present in multiple myeloma and have increasingly demonstrated critical roles for tumor development and relapse to standard therapies. Accumulating evidence suggests that the histone methyltransferase EZH2 is aberrantly active in MM. We tested the efficacy of EZH2 specific inhibitors in a large panel of human MM cell lines (HMCLs) and found that only a subset of HMCLs demonstrate single agent sensitivity despite ubiquitous global H3K27 demethylation...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29773601/combinatorial-targeting-of-xpo1-and-flt3-exerts-synergistic-anti-leukemia-effects-through-induction-of-differentiation-and-apoptosis-in-flt3-mutated-acute-myeloid-leukemias-from-concept-to-clinical-trial
#5
Weiguo Zhang, Charlie Ly, Jo Ishizawa, Hong Mu, Vivian Ruvolo, Sharon Shacham, Naval Daver, Michael Andreeff
Targeted therapies against FLT3-mutated acute myeloid leukemia have shown limited clinical efficacy primarily because of the acquisition of secondary mutations in FLT3 and persistent activation of downstream pro-survival pathways such as MEK/ERK, PI3K/AKT, and STAT5. Activation of these additional kinases may also result in phosphorylation of tumor suppressor proteins promoting their nuclear export. Thus, co-targeting nuclear export proteins (i.e., XPO1) and FLT3 concomitantly may be therapeutically effective...
May 17, 2018: Haematologica
https://www.readbyqxmd.com/read/29772645/anticancer-activity-of-euplotin-c-isolated-from-the-marine-ciliate-euplotes-crassus-against-human-melanoma-cells
#6
Sara Carpi, Beatrice Polini, Giulio Poli, Gabriela Alcantara Barata, Stefano Fogli, Antonella Romanini, Tiziano Tuccinardi, Graziano Guella, Francesco Paolo Frontini, Paola Nieri, Graziano Di Giuseppe
Cutaneous melanoma is the most serious type of skin cancer, so new cytotoxic weapons against novel targets in melanoma are of great interest. Euplotin C (EC), a cytotoxic secondary metabolite of the marine ciliate Euplotes crassus , was evaluated in the present study on human cutaneous melanoma cells to explore its anti-melanoma activity and to gain more insight into its mechanism of action. EC exerted a marked cytotoxic effect against three different human melanoma cell lines (A375, 501Mel and MeWo) with a potency about 30-fold higher than that observed in non-cancer cells (HDFa cells)...
May 16, 2018: Marine Drugs
https://www.readbyqxmd.com/read/29772386/novel-anticancer-hybrids-from-diazen-1-ium-1-2-diolate-nitric-oxide-donor-and-ros-inducer-plumbagin-design-synthesis-and-biological-evaluations
#7
Na Bao, Jinfeng Ou, Na Li, Pian Zou, Jianbo Sun, Li Chen
High levels of both nitric oxide (NO) and reactive oxygen species (ROS) could act as pro-apoptotic signals in cancerous cells. In this study, we conjugated diazeniumdiolates (NONOates), an important class of NO donors, with a natural occurring plumbagin (PL) which is primarily an excellent ROS inducer. Herein, a total of 12 novel plumbagin/NONOate hybrids have been synthesized and evaluated for their inhibitory effects on a panel of human cancer cell lines (MDA-MB-231, A549, HepG2 and HCT-116 cells) and two normal human cells (HK-2 and WRL-68 cells)...
April 25, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29770915/cytolytic-activity-score-to-assess-anticancer-immunity-in-colorectal-cancer
#8
Sumana Narayanan, Tsutomu Kawaguchi, Li Yan, Xuan Peng, Qianya Qi, Kazuaki Takabe
BACKGROUND: Elevated tumor-infiltrating lymphocytes (TILs) within the tumor microenvironment is a known positive prognostic factor in colorectal cancer (CRC). We hypothesized that since cytotoxic T cells release cytolytic proteins such as perforin (PRF1) and pro-apoptotic granzymes (GZMA) to attack cancer cells, a cytolytic activity score (CYT) would be a useful tool to assess anticancer immunity. METHODS: Genomic expression data were obtained from 456 patients from The Cancer Genome Atlas (TCGA)...
May 16, 2018: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/29770533/nctd-enhances-antitumor-immunity-of-gm-csf-prostate-cancer-cells-vaccine-by-inducing-apoptosis-of-regulatory-t-cells
#9
Lijun Mo, Xinji Zhang, Xiaojun Shi, Lili Wei, Dianpeng Zheng, Hongwei Li, Jimin Gao, Jinlong Li, Zhiming Hu
Norcantharidin (NCTD) is a promising antitumor drug with low toxicity. It was reported to be able to regulate immunity, but the mechanism is not yet clear. Here we explored whether NCTD could enhance the antitumor immunity induced by prostate cancer cells vaccine. The results in vitro study showed that NCTD induced apoptosis and inhibited proliferation of Tregs. Mechanistic research showed that NCTD inhibited Akt activation and activated FOXO1 transcription, resulting in pro-apoptotic effect. The results in vivo study showed that more tumor-infiltrating Tregs existed within peripheral blood and tumor tissue after treating with the vaccine...
May 16, 2018: Cancer Science
https://www.readbyqxmd.com/read/29769419/heart-rate-reduction-with-ivabradine-in-the-early-phase-of-atherosclerosis-is-protective-in-the-endothelium-of-apoe-deficient-mice
#10
G Aquila, M B Morelli, F Vieceli Dalla Sega, F Fortini, P Nigro, C Caliceti, M Ferracin, M Negrini, A Pannuti, M Bonora, P Pinton, R Ferrari, P Rizzo
Ivabradine, a heart rate reducing agent, protects the vascular system by unidentified mechanisms. We sought to determine the effects of the treatment with ivabradine, started before plaque formation, on early transcriptional changes and endothelium lesions in regions of aorta subjected to disturbed blood flow. Six week-old apolipoprotein E-deficient (ApoE-/- ) mice, fed a low-fat diet, were treated with ivabradine to determine the effect on transcriptional changes (2-and 4-week treatment) and on lesions formation (19-week treatment) in the endothelium of the aortic arch...
February 2018: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/29769319/repeated-exposure-of-epithelial-cells-to-apoptotic-cells-induces-the-specific-selection-of-an-adaptive-phenotype-implications-for-tumorigenesis
#11
Lanfei Feng, Snezana Vujicic, Michael E Dietrich, Natalia Litbarg, Suman Setty, Angelika Antoni, Joyce Rauch, Jerrold S Levine
The consequences of apoptosis extend beyond mere death of the cell. We have shown that receptor-mediated recognition of apoptotic target cells by viable kidney proximal tubular epithelial cells (PTECs) inhibits PTEC proliferation, growth, and survival. Here we tested the hypothesis that continual exposure to apoptotic targets can induce a phenotypic change in responding PTECs, as in other instances of natural selection. In particular, we demonstrate that repeated exposure to apoptotic targets leads to emergence of a PTEC line (denoted BU...
May 16, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29767235/inhibition-of-microrna%C3%A2-16-protects-mesenchymal-stem-cells-against-apoptosis
#12
Jiang Rui, Shaohong Fang, Yongchen Wang, Bo Lv, Bo Yu, Shufeng Li
Bone marrow‑derived mesenchymal stem cells (BM‑MSCs) have been used in experimental research and clinical trials for heart function restoration and cardiomyocyte regeneration. However, due to a hostile microenvironment created by ischemia, hypoxia and pro‑inflammatory factors, the survival rate of implanted BM‑MSCs remains low. Therefore, strategies that can promote BM‑MSC survival and prevent apoptosis are required. Previous studies have reported that microRNA‑16 (miR‑16) can inhibit cell proliferation by targeting several proteins and signal pathway, not only by inducing apoptosis...
May 11, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29765535/effects-of-cb2-and-trpv1-receptors-stimulation-in-pediatric-acute-t-lymphoblastic-leukemia
#13
Francesca Punzo, Iolanda Manzo, Chiara Tortora, Elvira Pota, Velia D' Angelo, Giulia Bellini, Alessandra Di Paola, Federica Verace, Fiorina Casale, Francesca Rossi
T-Acute Lymphoblastic Leukemia (T-ALL) is less frequent than B-ALL, but it has poorer outcome. For this reason new therapeutic approaches are needed to treat this malignancy. The Endocannabinoid/Endovanilloid (EC/EV) system has been proposed as possible target to treat several malignancies, including lymphoblastic diseases. The EC/EV system is composed of two G-Protein Coupled Receptors (CB1 and CB2), the Transient Potential Vanilloid 1 (TRPV1) channel, their endogenous and exogenous ligands and enzymes. CB1 is expressed mainly in central nervous system while CB2 predominantly on immune and peripheral cells, therefore we chose to selectively stimulate CB2 and TRPV1...
April 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29765202/inhibition-of-human-prostate-cancer-pc-3-cells-and-targeting-of-pc-3-derived-prostate-cancer-stem-cells-with-koenimbin-a-natural-dietary-compound-from-murraya-koenigii-l-spreng
#14
Behnam Kamalidehghan, Soudeh Ghafouri-Fard, Elahe Motevaseli, Fatemeh Ahmadipour
Background: Inhibition of prostate cancer stem cells (PCSCs) is an efficient curative maintenance protocol for the prevention of prostate cancer. The objectives of this study were to assess the efficiency of koenimbin, a major biologically active component of Murraya koenigii (L) Spreng, in the suppression of PC-3 cells and to target PC-3-derived cancer stem cells (CSCs) through apoptotic and CSC signaling pathways in vitro. Materials and methods: The antiproliferative activity of koenimbin was examined using MTT, and the apoptotic detection was carried out by acridine orange/propidium iodide (AO/PI) double-staining and multiparametric high-content screening (HCS) assays...
2018: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/29764928/ovarian-steroid-dependence-of-endoplasmic-reticulum-stress-involvement-in-endometrial-cell-apoptosis-during-the-human-endometrial-cycle
#15
Jong Yeob Choi, Min Wha Jo, Eun Young Lee, Dong-Yun Lee, Doo Seok Choi
Endoplasmic reticulum (ER) stress is a common cellular stress response that enhances apoptosis to trigger cell death. However, recent studies have shown that estrogen suppresses apoptosis by inhibiting ER stress in some cell types, suggesting that ER stress-induced apoptosis is regulated by ovarian steroid hormones. In endometrial cells, ER stress may also be controlled by ovarian steroid hormones and could be involved in apoptosis induction during the menstrual cycle. To test this hypothesis, we elucidate whether ER stress is regulated by ovarian steroid hormones in human endometrial cells and if it is involved in apoptosis induction...
June 2018: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/29764852/combined-hdac-and-bromodomain-protein-inhibition-reprograms-tumor-cell-metabolism-and-elicits-synthetic-lethality-in-glioblastoma
#16
Yiru Zhang, Chiaki Tsuge Ishida, Wataru Ishida, Sheng-Fu L Lo, Junfei Zhao, Chang Shu, Elena Bianchetti, Giulio Kleiner, Maria Sanchez-Quintero, Catarina M Quinzii, Mike-Andrew Westhoff, Georg Karpel-Massler, Peter Canoll, Markus D Siegelin
PURPOSE: Glioblastoma remain a challenge in oncology in part due to tumor heterogeneity. EXPERIMENTAL DESIGN: Patient-derived xenograft and stem-like glioblastoma cells were used as the primary model systems. RESULTS: Based on a transcriptome and subsequent gene set enrichment analysis (GSEA), we show by using clinically validated compounds that combined histone deacetylase (HDAC) inhibition and Bromodomain protein (BRD) inhibition results in pronounced synergistic reduction in cellular viability in patient-derived xenograft and stem-like glioblastoma cells...
May 15, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29764561/mir-204-acts-as-a-potential-therapeutic-target-in-acute-myeloid-leukemia-by-increasing-birc6-mediated-apoptosis
#17
Zhiguo Wang, Hong Luo, Zehui Fang, Yanling Fan, Xiaojuan Liu, Yujing Zhang, Shuping Rui, Yafeng Chen, Luojia Hong, Jincheng Gao, Mei Zhang
Acute myeloid leukemia (AML) is one of the most common hematological malignancies all around the world. MicroRNAs have been determined to contribute various cancers initiation and progression, including AML. Although microRNA-204 (miR-204) exerts anti-tumor effects in several kinds of cancers, its function in AML remains unknown. In the present study, we assessed miR-204 expression in AML blood samples and cell lines. We also investigated the effects of miR-204 on cellular function of AML cells and the underlying mechanisms of the action of miR-204...
May 16, 2018: BMB Reports
https://www.readbyqxmd.com/read/29763296/delivery-of-a-pro-apoptotic-peptide-to-egfr-positive-cancer-cells-by-a-cyclic-peptide-mimicking-the-dimerization-arm-structure-of-egfr
#18
Kei Toyama, Wataru Nomura, Takuya Kobayakawa, Hirokazu Tamamura
A cyclic decapeptide, CQTPYYMNTC (1), which mimics the dimerization arm of the EGF receptor (EGFR), was previously found to be captured into cells. We have sought to investigate the promising potential of this peptide as an intracellular delivery vehicle directed to EGFR-positive cells. The selectivity of Peptide 1 to the EGFR was confirmed by a positive correlation between the expression level of the receptor and the cellular uptake of Peptide 1 as shown by siRNA knockdown of the EGFR. The pro-apoptotic domain (PAD) peptide, ([KLAKLAK]2), has limited use due to a deficiency of cell membrane permeability resulting from cationic sequences and lack of specificity for cancer cells...
May 15, 2018: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29761559/conditional-depletion-of-gsk3b-protects-oligodendrocytes-from-apoptosis-and-lessens-demyelination-in-the-acute-cuprizone-model
#19
Bin Xing, Lauren E Brink, Kelly Maers, Mara L Sullivan, Richard J Bodnar, Donna B Stolz, Franca Cambi
Apoptosis is recognized as the main mechanism of oligodendrocyte loss in Multiple Sclerosis caused either by immune mediated injury (Barnett & Prineas, ) or a direct degenerative process (oligodendrogliapathy; Lucchinetti et al., ). Cuprizone induced demyelination is the result of non-immune mediated apoptosis of oligodendrocytes (OL) and represents a model of oligodendrogliapathy (Simmons, Pierson, Lee, & Goverman, ). Glycogen Synthase Kinase (GSK) 3b has been shown to be pro-apoptotic for cells other than OL...
May 15, 2018: Glia
https://www.readbyqxmd.com/read/29760954/the-p53-activator-overcomes-resistance-to-alk-inhibitors-by-regulating-p53-target-selectivity-in-alk-driven-neuroblastomas
#20
Makoto Miyazaki, Ryo Otomo, Yuko Matsushima-Hibiya, Hidenobu Suzuki, Ayana Nakajima, Naomi Abe, Arata Tomiyama, Koichi Ichimura, Koichi Matsuda, Toshiki Watanabe, Takahiro Ochiya, Hitoshi Nakagama, Ryuichi Sakai, Masato Enari
Anaplastic lymphoma kinase (ALK) is an oncogenic receptor tyrosine kinase that is activated by gene amplification and mutation in neuroblastomas. ALK inhibitors can delay the progression of ALK-driven cancers, but are of limited use owing to ALK inhibitor resistance. Here, we show that resistance to ALK inhibitor in ALK-driven neuroblastomas can be attenuated by combination treatment with a p53 activator. Either ALK inhibition or p53 activator treatment induced cell cycle arrest, whereas combination treatment induced apoptosis, and prevented tumour relapse both in vitro and in vivo...
2018: Cell Death Discovery
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