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https://www.readbyqxmd.com/read/30024813/the-chk1-inhibitor-sra737-synergizes-with-parp1-inhibitors-to-kill-carcinoma-cells
#1
Laurence Booth, Jane Roberts, Andrew Poklepovic, Paul Dent
Inhibitors of PARP1 are approved therapeutic agents in ovarian carcinomas. We determined whether the novel clinically relevant CHK1 inhibitor SRA737 interacted with PARP1 inhibitors to kill carcinoma cells. In multiple mammary and ovarian cancer lines SRA737 synergized with the PARP1 inhibitors olaparib and niraparib to cause cell death. The [SRA737 + niraparib] drug combination activated an ATM-AMPK-ULK1-mTOR pathway which resulted in the formation of autophagosomes, temporally followed by autolysosome formation...
July 19, 2018: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/30024106/transcriptome-analysis-of-cho-cell-size-increase-during-a-fed-batch-process
#2
Xiao Pan, Abdulaziz A Alsayyari, Ciska Dalm, Jos A Hageman, René H Wijffels, Dirk E Martens
In a CHO cell fed-batch process arrest of cell proliferation and an almost threefold increase in cell size occurred, which was associated with an increase in cell specific productivity. In this study, transcriptome analysis is performed to identify the molecular mechanisms associated with this. Cell cycle analysis reveals that the cells are arrested mainly in the G0 /G1 phase. The cell cycle arrest is associated with significant up-regulation of cyclin-dependent kinases inhibitors (CDKNs) and down-regulation of cyclin-dependent kinases (CDKs) and cyclins...
July 19, 2018: Biotechnology Journal
https://www.readbyqxmd.com/read/30023463/combination-of-bez235-and-metformin-has-synergistic-effect-on-cell-viability-in-colorectal-cancer-cells
#3
Taewan Kim, Taehyung Kim, Soonyoung Choi, Hyeran Ko, Deokbae Park, Youngki Lee
Patients with type II diabetes mellitus are more susceptible to colorectal cancer (CRC) incidence than non-diabetics. The anti-diabetic drug metformin is most commonly prescribed for the treatment of this disease and has recently shown antitumor effect in preclinical studies. The aberrant mutational activation in the components of RAS/RAF/MEK/ERK and PI3K/AKT/mTOR signaling pathway is very frequently observed in CRC. We previously reported that metformin inhibits the phosphorylation of ERK and BEZ235, a dual inhibitor of PI3K and mTOR, has anti-tumor activity against HCT15 CRC cells harboring mutations of KRAS and PIK3CA...
June 2018: Balsaeng'gwa Saengsig
https://www.readbyqxmd.com/read/30022363/ppar%C3%AE-agonist-pgz-attenuates-ova-induced-airway-inflammation-and-airway-remodeling-via-rgs4-signaling-in-mouse-model
#4
Xia Meng, Xinrong Sun, Yonghong Zhang, Hongyang Shi, Wenjing Deng, Yanqin Liu, Guizuo Wang, Ping Fang, Shuanying Yang
Peroxisome proliferator-activated receptor-γ (PPARγ) agonist pioglitazone (PGZ) exhibits potential protective effects in asthma. Recently, regulator of G protein 4 (RGS4) has been reported to be associated with immunological and inflammatory responses. However, no evidence has shown the influence of PPARγ on RGS4 expression in airway disorders. In this study, BALB/c mice received ovalbumin (OVA) sensitization followed by OVA intranasal challenge for 90 days to establish a chronic asthma mouse model. Accompanied with OVA challenge, the mice received administration of PPARγ agonist PGZ (10 mg/kg) intragastrically or RGS4 inhibitor CCG 63802 (0...
July 19, 2018: Inflammation
https://www.readbyqxmd.com/read/30022281/autophagy-blockade-sensitizes-human-head-and-neck-squamous-cell-carcinoma-towards-cyt997-through-enhancing-excessively-high-reactive-oxygen-species-induced-apoptosis
#5
Lixia Gao, Xiangdong Zhao, Liwei Lang, Chloe Shay, W Andrew Yeudall, Yong Teng
The functional relationship between apoptosis and autophagy in anticancer drug treatment is extremely complex, and the molecular machinery is obscure. This study aims to investigate the efficacy of CYT997, a novel microtubule-disrupting agent, in head and neck squamous cell carcinomas (HNSCCs) and complete the autophagy-apoptosis puzzle involved in drug action. We report here that CYT997 exhibits anticancer activity by triggering oxidative stress-associated apoptosis in HNSCC cells. Interestingly, upregulation of autophagy by mTOR-dependent pathways appears to have a cytoprotective role in preventing apoptosis by inhibiting CYT997-induced excessively high levels of reactive oxygen species (ROS)...
July 18, 2018: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/30022232/neuroprotective-effect-of-vildagliptin-against-cerebral-ischemia-in-rats
#6
Salma A El-Marasy, Rehab F Abdel-Rahman, Reham M Abd-Elsalam
Stroke is the leading cause of death worldwide. Dipeptidyl peptidase-4 (DPP-4) inhibitors are a class of anti-diabetic drugs for treatment of type-2 diabetes mellitus. The aim of this study is to evaluate the possible neuroprotective effect of a dipeptidyl peptidase-4 inhibitor, vildagliptin, independent of its anti-diabetic properties in non-diabetic rats subjected to cerebral ischemia. Anesthetized Wistar rats were subjected to either left middle cerebral artery occlusion (MCAO) or sham operation followed by reperfusion after 30 min of MCAO...
July 18, 2018: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/30021906/kaposi-sarcoma-associated-herpesvirus-latency-locus-renders-b-cells-hyperresponsive-to-secondary-infections
#7
Sang-Hoon Sin, Anthony B Eason, Rachele Bigi, Yongbaek Kim, SunAh Kang, Kelly Tan, Tischan A Seltzer, Raman Venkataramanan, Hyowon An, Dirk P Dittmer
Kaposi Sarcoma-associated herpesvirus (KSHV) KSHV induces B cell hyperplasia and neoplasia such as multicentric Castleman's disease (MCD) and primary effusion lymphoma (PEL). To explore KSHV-induced B cell reprogramming in vivo , we expressed the KSHV latency locus, inclusive of all viral miRNAs, in B cells of transgenic mice in the absence of the inhibitory FcγRIIB receptor. The BALB/c strain was chosen as this is the preferred model to study B cell differentiation. The mice developed hyperglobulinemia, plasmacytosis, and B lymphoid hyperplasia...
July 18, 2018: Journal of Virology
https://www.readbyqxmd.com/read/30021885/pp2a-inhibition-is-a-druggable-mek-inhibitor-resistance-mechanism-in-kras-mutant-lung-cancer-cells
#8
Otto Kauko, Caitlin M O'Connor, Evgeny Kulesskiy, Jaya Sangodkar, Anna Aakula, Sudeh Izadmehr, Laxman Yetukuri, Bhagwan Yadav, Artur Padzik, Teemu Daniel Laajala, Pekka Haapaniemi, Majid Momeny, Taru Varila, Michael Ohlmeyer, Tero Aittokallio, Krister Wennerberg, Goutham Narla, Jukka Westermarck
Kinase inhibitor resistance constitutes a major unresolved clinical challenge in cancer. Furthermore, the role of serine/threonine phosphatase deregulation as a potential cause for resistance to kinase inhibitors has not been thoroughly addressed. We characterize protein phosphatase 2A (PP2A) activity as a global determinant of KRAS-mutant lung cancer cell resistance across a library of >200 kinase inhibitors. The results show that PP2A activity modulation alters cancer cell sensitivities to a large number of kinase inhibitors...
July 18, 2018: Science Translational Medicine
https://www.readbyqxmd.com/read/30021391/comprehensive-anti-tumor-effect-of-brusatol-through-inhibition-of-cell-viability-and-promotion-of-apoptosis-caused-by-autophagy-via-the-pi3k-akt-mtor-pathway-in-hepatocellular-carcinoma
#9
Ruifan Ye, Ninggao Dai, Qikuan He, Pengyi Guo, Yukai Xiang, Qiong Zhang, Zhong Hong, Qiyu Zhang
Brusatol, a natural quassinoid isolated from a traditional Chinese herbal medicine known as Bruceae Fructus, has recently been reported to possess powerful cytotoxic effects against various cancer cell lines, highlighting its potential as an anti-cancer drug. However, the precise molecular mechanisms by which Brusatol exerts its anti-cancer effects remain poorly understood in hepatocellular carcinoma (HCC). In this study, we demonstrated that Brusatol inhibited cell viability, proliferation and induced apoptosis in liver cancer lines...
September 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/30021100/mir-212-and-mtor-form-a-regulation-loop-to-modulate-autophagy-in-colorectal-adenoma-ht-29-cells
#10
Changxue Ji, Shuai Ju, Jinwei Qiang
Autophagy is a conserved lysosomal degradation pathway that regulates cell survival and death in order to maintain cellular homeostasis. Dysfunctional autophagy is associated with different types of cancer, making it an attractive therapeutic target. Mammalian target of rapamycin (mTOR) signaling negatively regulates autophagy and suppresses the efficacy of certain cancer therapeutic agents. NVP-BEZ235 is a dual inhibitor of the PI3K/mTOR signaling pathway and exhibits anti-cancer activities; it also induced autophagy and inhibited proliferation in colorectal adenoma HT-29 cells...
June 2018: Discovery Medicine
https://www.readbyqxmd.com/read/30020994/amino-acid-deprivation-triggers-a-novel-gcn2-independent-response-leading-to-the-transcriptional-reactivation-of-non-native-dna-sequences
#11
Annarosaria De Vito, Massimo Lazzaro, Ilaria Palmisano, Davide Cittaro, Michela Riba, Dejan Lazarevic, Makoto Bannai, Davide Gabellini, Maria Vittoria Schiaffino
In a variety of species, reduced food intake, and in particular protein or amino acid (AA) restriction, extends lifespan and healthspan. However, the underlying epigenetic and/or transcriptional mechanisms are largely unknown, and dissection of specific pathways in cultured cells may contribute to filling this gap. We have previously shown that, in mammalian cells, deprivation of essential AAs (methionine/cysteine or tyrosine) leads to the transcriptional reactivation of integrated silenced transgenes, including plasmid and retroviral vectors and latent HIV-1 provirus, by a process involving epigenetic chromatic remodeling and histone acetylation...
2018: PloS One
https://www.readbyqxmd.com/read/30020826/acute-iodine-deficiency-induces-a-transient-vegf-dependent-microvascular-response-in-mammary-glands-involving-hif-1-ros-and-mtor
#12
Jessica Vanderstraeten, Hanane Derradji, Pierre Sonveaux, Ides Colin, Marie-Christine Many, Anne-Catherine Gérard
Iodine deficiency (ID), which affects almost two billion people worldwide, is associated with breast pathologies such as fibrosis in human and induces breast atypia in animal models. Because ID induces vascular activation in the thyroid, another iodide-uptaking organ, and as breast is also sensitive to ID, we aimed to characterize ID-induced effects on the breast microvasculature in vivo and in two different breast cell lines in vitro. Virgin and lactating NMRI mice received an iodide-deficient diet and a Na+ /I- symporter inhibitor for one to 20 days...
July 18, 2018: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/30019485/rapamycin-ameliorates-psoriasis-by-regulating-the-expression-and-methylation-levels-of-tropomyosin-via-erk1-2-and-mtor-pathways-in-vitro-and-in-vivo
#13
Minhong Gao, Xiaoqing Si
Psoriasis is a chronic inflammatory disease, affecting more than millions of people in the world. Recently, the mTOR inhibitor rapamycin (RAPA) was reported to be involved in the pathogenesis of psoriasis. However, the underlying mechanism remains unclear. Hematoxylin-eosin staining was used to examine the effects of RAPA on inflammatory level of lesional tissues from psoriasis patients and animal models. Quantitative real-time PCR, immunohistochemistry and western blot assay were performed to assess the effects of RAPA on Tropomyosins (TPMs) expression in psoriasis patients, cell models, and animal models...
July 17, 2018: Experimental Dermatology
https://www.readbyqxmd.com/read/30018708/topiramate-exhibits-anti-tumorigenic-and-metastatic-effects-in-ovarian-cancer-cells
#14
Guangxu Xu, Ziwei Fang, Leslie H Clark, Wenchuan Sun, Yajie Yin, Rong Zhang, Stephanie A Sullivan, Arthur-Quan Tran, Weimin Kong, Jiandong Wang, Chunxiao Zhou, Victoria L Bae-Jump
Ovarian cancer is one of the leading causes of cancer related deaths among women worldwide, with an overall 5-year survival of only 30-40%. Carbonic anhydrases are up-regulated in many types of cancer and play an important role in tumor progression and metastasis. Carbonic anhydrase 9 has been implicated as a potential anti-tumorigenic target. Topiramate (TPM) is a potent inhibitor of carbonic anhydrase isozymes, including carbonic anhydrase 9, and has been shown to have anti-tumorigenic activity in several cancer types...
2018: American Journal of Translational Research
https://www.readbyqxmd.com/read/30018387/buparlisib-is-a-brain-penetrable-pan-pi3k-inhibitor
#15
Mark C de Gooijer, Ping Zhang, Levi C M Buil, Ceren H Çitirikkaya, Nishita Thota, Jos H Beijnen, Olaf van Tellingen
Characterization of the genomic landscapes of intracranial tumours has revealed a clear role for the PI3K-AKT-mTOR pathway in tumorigenesis and tumour maintenance of these malignancies, making phosphatidylinositol 3-kinase (PI3K) inhibition a promising therapeutic strategy for these tumours. Buparlisib is a novel pan-PI3K inhibitor that is currently in clinical development for various cancers, including primary and secondary brain tumours. Importantly however, earlier studies have revealed that sufficient brain penetration is a prerequisite for antitumor efficacy against intracranial tumours...
July 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/30015913/active-fraction-of-clove-induces-apoptosis-via-pi3k-akt-mtor-mediated-autophagy-in-human-colorectal-cancer-hct-116-cells
#16
Minghua Liu, Ge Zhao, Dan Zhang, Weixiao An, Honglin Lai, Xiaofang Li, Shousong Cao, Xiukun Lin
Previous studies by our group have demonstrated that extract of clove exhibits potent anticancer effects in vitro and in vivo. In the present study, the effect of an extracted and isolated active fraction of clove (AFC) on induction of cellular apoptosis in human colorectal cancer HCT-116 cells was investigated by morphological observation, flow cytometry, and western blotting analysis. The results revealed that AFC induced apoptosis of HCT-116 cells. AFC also induced autophagy, demonstrated by increased punctuate microtubule-associated protein 1A/1B-light chain 3 (LC3) staining, and LC3-II and Beclin-1 protein expression levels...
July 2, 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/30015881/microrna%C3%A2-155-promotes-ox%C3%A2-ldl%C3%A2-induced-autophagy-in-human-umbilical-vein-endothelial-cells-by-targeting-the-pi3k-akt-mtor-pathway
#17
Shuangshuang Yin, Shaonan Yang, Xudong Pan, Aijun Ma, Juanjuan Ma, Haotian Pei, Yi Dong, Shu Li, Wei Li, Xinran Bi
Endothelial cell autophagy has a protective role in inhibiting inflammation and preventing the development of atherosclerosis, which may be regulated by microRNA (miR)‑155. The present study aimed to investigate the mechanisms of autophagy in the development of atherosclerosis. Human umbilical vein endothelial cells model in vitro and using oxidized low‑density lipoprotein (ox‑LDL) stimulated cells to simulate the atherosclerosis. MiR‑155 mimics, miR‑155 inhibitors, and a negative control were respectively transfected in human umbilical vein endothelial cells to analyzed alterations in the expression of miR‑155...
June 29, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/30015406/topical-rapamycin-sirolimus-for-the-treatment-of-uncomplicated-tufted-angiomas-in-two-children-and-review-of-the-literature
#18
Angela Burleigh, Nordau Kanigsberg, Joseph M Lam
The mTOR inhibitor rapamycin is used systemically for the treatment of vascular lesions. We report the first use of topical rapamycin for the successful treatment of two cases of tufted angioma. The evidence for the use of topical rapamycin in other dermatologic conditions is summarized to aid in clinical decision making on preparations and anticipated side effects.
July 17, 2018: Pediatric Dermatology
https://www.readbyqxmd.com/read/30013485/mir-21-protects-against-ischemia-reperfusion-induced-acute-kidney-injury-by-preventing-epithelial-cell-apoptosis-and-inhibiting-dendritic-cell-maturation
#19
Nana Song, Ting Zhang, XiaLian Xu, Zhihui Lu, Xiaofang Yu, Yi Fang, Jiachang Hu, Ping Jia, Jie Teng, Xiaoqiang Ding
Renal tubular injury and innate immune responses induced by hypoxia contribute to acute kidney injury. Accumulating evidence suggests that miR-21 overexpression protects against kidney ischemia injury. Additionally, miR-21 emerges as a key inhibitor in dendritic cell maturation. Thus, we hypothesized that miR-21 protects the kidney from IR injury by suppressing epithelial cell damage and inflammatory reaction. In this study, we investigated effects of miR-21 and its signaling pathways (PTEN/AKT/mTOR/HIF, PDCD4/NFκ-B) on kidney ischemia/reperfusion (IR) injury in vitro and in vivo ...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/30013478/how-tumor-cells-choose-between-epithelial-mesenchymal-transition-and-autophagy-to-resist-stress-therapeutic-implications
#20
REVIEW
Fabrizio Marcucci, Cristiano Rumio
Tumor cells undergo epithelial-mesenchymal transition (EMT) or macroautophagy (hereafter autophagy) in response to stressors from the microenvironment. EMT ensues when stressors act on tumor cells in the presence of nutrient sufficiency, and mechanistic target of rapamycin (mTOR) appears to be the crucial signaling node for EMT induction. Autophagy, on the other hand, is induced in the presence of nutrient deprivation and/or stressors from the microenvironment with 5' adenosine monophosphate-activated protein kinase (AMPK) playing an important, but not exclusive role, in autophagy induction...
2018: Frontiers in Pharmacology
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