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https://www.readbyqxmd.com/read/29340049/pharmacological-treatment-with-inhibitors-of-nuclear-export-enhances-the-antitumor-activity-of-docetaxel-in-human-prostate-cancer
#1
Giovanni Luca Gravina, Andrea Mancini, Alessandro Colapietro, Francesco Marampon, Roberta Sferra, Simona Pompili, Leda Assunta Biordi, Roberto Iorio, Vincenzo Flati, Christian Argueta, Yosef Landesman, Michael Kauffman, Sharon Shacham, Claudio Festuccia
Background and aims: Docetaxel (DTX) modestly increases patient survival of metastatic castration-resistant prostate cancer (mCRPC) due to insurgence of pharmacological resistance. Deregulation of Chromosome Region Maintenance (CRM-1)/ exportin-1 (XPO-1)-mediated nuclear export may play a crucial role in this phenomenon. Material and methods: Here, we evaluated the effects of two Selective Inhibitor of Nuclear Export (SINE) compounds, selinexor (KPT-330) and KPT-251, in association with DTX by using 22rv1, PC3 and DU145 cell lines with their...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29331082/mechanistic-target-of-rapamycin-complex-1-and-2-in-human-temporal-lobe-epilepsy
#2
Delia M Talos, Leah M Jacobs, Sarah Gourmaud, Carlos A Coto, Hongyu Sun, Kuei-Cheng Lim, Timothy H Lucas, Kathryn A Davis, Maria Martinez-Lage, Frances E Jensen
OBJECTIVE: Temporal lobe epilepsy (TLE) is a chronic epilepsy syndrome defined by seizures and progressive neurological disabilities, including cognitive impairments, anxiety and depression. Here, human TLE specimens were investigated focusing on the mechanistic target of rapamycin (mTOR) Complex 1 (mTORC1) and Complex 2 (mTORC2) activities in the brain, as both pathways may represent unique targets for treatment. METHODS: Surgically resected hippocampal and temporal lobe samples from therapy-resistant TLE patients were analyzed by Western blotting to quantify the expression of established mTORC1 and mTORC2 activity markers and upstream or downstream signaling pathways involving the two complexes...
January 13, 2018: Annals of Neurology
https://www.readbyqxmd.com/read/29330285/foxo-dependent-par-4-upregulation-prevents-long-term-survival-of-residual-cells-following-pi3k-akt-inhibition
#3
Jeffrey S Damrauer, Stephanie N Phelps, Katie Amuchastegui, Ryan Lupo, Nathaniel W Mabe, Andrea Walens, Benjamin R Kroger, James V Alvarez
Tumor recurrence is a leading cause of death and is thought to arise from a population of residual cells that survive treatment. These residual cancer cells can persist, locally or at distant sites, for years or decades. Therefore, understanding the pathways that regulate residual cancer cell survival may suggest opportunities for targeting these cells to prevent recurrence. Previously it was observed that the pro-apoptotic protein (PAWR/Par-4) negatively regulates residual cell survival and recurrence in mice and humans...
January 12, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29326312/foxo3a-forkhead-transcription-factor-o-subfamily-member-3a-links-vascular-smooth-muscle-cell-apoptosis-matrix-breakdown-atherosclerosis-and-vascular-remodeling-through-a-novel-pathway-involving-mmp13-matrix-metalloproteinase-13
#4
Haixiang Yu, Adam Fellows, Kirsty Foote, Zhaoqing Yang, Nichola Figg, Trevor Littlewood, Martin Bennett
OBJECTIVE: Vascular smooth muscle cell (VSMC) apoptosis accelerates atherosclerosis and promotes breakdown of the extracellular matrix, but the mechanistic links between these 2 processes are unknown. The forkhead protein FOXO3a (forkhead transcription factor O subfamily member 3a) is activated in human atherosclerosis and induces a range of proapoptotic and other transcriptional targets. We, therefore, determined the mechanisms and consequences of FOXO3a activation in atherosclerosis and arterial remodeling after injury...
January 11, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29323335/tanshinol-alleviates-impaired-bone-formation-by-inhibiting-adipogenesis-via-klf15-ppar%C3%AE-2-signaling-in-gio-rats
#5
Ya-Jun Yang, Zhu Zhu, Dong-Tao Wang, Xin-le Zhang, Yu-Yu Liu, Wen-Xiu Lai, Yu-Lin Mo, Jin Li, Yan-Long Liang, Zhuo-Qing Hu, Yong-Jie Yu, Liao Cui
Glucocorticoid (GC)-induced osteoporosis (GIO) is characterized by impaired bone formation, which can be alleviated by tanshinol, an aqueous polyphenol isolated from Salvia miltiorrhiza Bunge. In this study we investigated the molecular mechanisms underlying GC-induced modulation of osteogenesis as well as the possibility of using tanshinol to interfere with GIO. Female SD rats aged 4 months were orally administered distilled water (Con), prednisone (GC, 5 mg·kg-1·d-1), GC plus tanshinol (Tan, 16 mg·kg-1·d-1) or GC plus resveratrol (Res, 5 mg·kg-1·d-1) for 14 weeks...
January 11, 2018: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/29322615/melatonin-protects-against-a%C3%AE-induced-neurotoxicity-in-primary-neurons-via-mir-132-pten-akt-foxo3a-pathway
#6
Yue Zhao, Ranran Zhao, Jintao Wu, Qian Wang, Kunkun Pang, Qingqing Shi, Qing Gao, Yanlai Hu, Xiaoguang Dong, Jing Zhang, Jinhao Sun
Alzheimer's disease (AD) is a kind of neurodegenerative disorder associated with age. Investigations suggest that amyliod-β (Aβ) is implicated in the pathogenesis of AD. The accumulation of Aβ in the brain causes oxidative stress and synaptic toxicity, leads to synaptic dysfunction and neuronal death. Previous investigations suggest that melatonin an endogenous hormone can counteract Aβ-induced neurotoxicity. However, the molecular mechanisms of Aβ-induced toxicity and melatonin treatment remain elusive...
January 11, 2018: BioFactors
https://www.readbyqxmd.com/read/29315934/effect-of-euk-134-on-akt-mtor-signaling-in-the-rat-soleus-during-7-days-of-mechanical-unloading
#7
J Matthew Kuczmarski, Jeff M Hord, Yang Lee, Vinicius Guzzoni, Dinah Rodriguez, Matthew S Lawler, Erika L Garcia-Villatoro, Dylan Holly, Patrick Ryan, Kristian Falcon, Marcela Garcia, Mariana Janini Gomes, James D Fluckey, John M Lawler
Mechanical unloading stimulates rapid changes in skeletal muscle morphology, characterized by atrophy of muscle fiber cross-sectional area (CSA) and a partial fiber-type shift from slow to fast-twitch. Recent studies revealed that oxidative stress contributes to activation of FoxO3a, proteolytic signaling and unloading-induced muscle atrophy via translocation of the mu-splice variant of neuronal nitric oxide synthase (nNOSμ) and activation of FoxO3a. Yet, there is limited understanding of the role of reactive oxygen species (ROS) on the Akt-mTOR pathway signaling during unloading...
January 8, 2018: Experimental Physiology
https://www.readbyqxmd.com/read/29312618/estrogen-receptor-signaling-mediates-leptin-induced-growth-of-breast-cancer-cells-via-autophagy-induction
#8
Pawan Kumar Raut, Dong Young Choi, Sang Hyun Kim, Jin Tae Hong, Taeg Kyu Kwon, Jee Heon Jeong, Pil-Hoon Park
Leptin, a hormone derived from adipose tissue, promotes growth of cancer cells via multiple mechanisms. Estrogen receptor signaling is also known to stimulate the growth of breast cancer cells. However, the involvement of estrogen receptor signaling in the oncogenic actions of leptin and its underlying mechanisms are not clearly understood. Herein, we investigated mechanisms for estrogen receptor signaling-mediated growth of breast cancer cells, particularly focusing on autophagy, which plays a crucial role in leptin-induced tumor growth...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29304479/microrna-140-5p-aggravates-doxorubicin-induced-cardiotoxicity-by-promoting-myocardial-oxidative-stress-via-targeting-nrf2-and-sirt2
#9
Lisha Zhao, Yan Qi, Lina Xu, Xufeng Tao, Xu Han, Lianhong Yin, Jinyong Peng
Clinical application of doxorubicin (DOX), an anthracycline antibiotic with potent anti- tumor effects, is limited because of its cardiotoxicity. However, its pathogenesis is still not entirely understood. The aim of this paper was to explore the mechanisms and new drug targets to treat DOX-induced cardiotoxicity. The in vitro model on H9C2 cells and the in vivo models on rats and mice were developed. The results showed that DOX markedly decreased H9C2 cell viability, increased the levels of CK, LDH, caused histopathological and ECG changes in rats and mice, and triggered myocardial oxidative damage via adjusting the levels of intracellular ROS, MDA, SOD, GSH and GSH-Px...
December 29, 2017: Redox Biology
https://www.readbyqxmd.com/read/29298131/a-systematic-review-of-p53-regulation-of-oxidative-stress-in-skeletal-muscle
#10
Kaitlyn Beyfuss, David A Hood
BACKGROUND: p53 is a tumor suppressor protein involved in regulating a wide array of signaling pathways. The role of p53 in the cell is determined by the type of imposed oxidative stress, its intensity and duration. The last decade of research has unravelled a dual nature in the function of p53 in mediating the oxidative stress burden. However, this is dependent on the specific properties of the applied stress and thus requires further analysis. METHODS: A systematic review was performed following an electronic search of Pubmed, Google Scholar, and ScienceDirect databases...
January 3, 2018: Redox Report: Communications in Free Radical Research
https://www.readbyqxmd.com/read/29282102/lncrna-ak023391-promotes-tumorigenesis-and-invasion-of-gastric-cancer-through-activation-of-the-pi3k-akt-signaling-pathway
#11
Yanxia Huang, Jing Zhang, Lidan Hou, Ge Wang, Hui Liu, Rui Zhang, Xiaoyu Chen, Jinshui Zhu
BACKGROUND: Patients with gastric cancer commonly have a poor prognosis, owing to its invasiveness and distant metastasis. Recent studies have confirmed the pivotal role of long non-coding RNAs (lncRNAs) in tumorigenesis and the progression of malignant tumors, including gastric cancer. However, little is known about the molecular mechanism by which lncRNA AK023391 contributes to gastric cancer. METHODS: A lncRNA microarray was used to identify the differentially expressed lncRNA AK023391 in gastric cancer and adjacent normal tissues...
December 28, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29274585/knockdown-of-the-long-non-coding-rna-hottip-inhibits-colorectal-cancer-cell-proliferation-and-migration-and-induces-apoptosis-by-targeting-sgk1
#12
Tianyou Liu, Tao Yu, Haiying Hu, Keping He
More and more long non-coding RNA (lncRNA) might be serve as molecular biomarkers for tumor cell progression. HOTTIP has been recently revealed as oncogenic regulator in several cancers. However, it remains unclear about whether and how HOTTIP regulates Colorectal cancer (CRC). In the present study, we assayed the expression of HOTTIP in CRC tissues and cell lines, and detected CRC cells (HCT-116 and SW620) proliferation, migration, and apoptosis when HOTTIP was knocked down. Furthermore, we discovered the underlying mechanism...
December 20, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29225211/changes-in-foxo-and-proinflammatory-cytokines-in-the-late-stage-of-immobilized-fast-and-slow-muscle-atrophy
#13
Takeshi Okamoto, Shuichi Machida
The present study aimed to examine the changes in the expression of Forkhead box protein O (FOXO) and proinflammatory cytokines in both slow-twitch soleus and fast-twitch plantaris muscles following cast immobilization. Male C57BL/6 mice were subjected to cast immobilization for 7 and 21 days. Cast immobilization increased FOXO3a mRNA and total protein expression in both the soleus and plantaris muscles. Although FOXO3a phosphorylation tended to increase in response to cast immobilization in both muscles, a significant increase was evident after 21 days of immobilization only in the soleus muscle...
2017: Biomedical Research
https://www.readbyqxmd.com/read/29223039/n-acetyl-l-cysteine-ameliorates-the-pm2-5-induced-oxidative-stress-by-regulating-sirt-1-in-rats
#14
Lu Yang, Zheng Duan, Xin Liu, Yadong Yuan
Silent information regulator 1 (SIRT1), a class III histone deacetylase, plays a major role in combating cellular oxidative stress injury. However, the role of SIRT1 in oxidative stress induced by particulate matter remains unclear. A total of 32 healthy male Sprague-Dawley rats were divided into PM2.5, PM2.5+NAC, filtered air (control), and filtered air+NAC (NAC control) groups. The expressions of MnSOD, SIRT1, and FOXO3a were examined at both transcriptional and protein levels. The expression levels of MnSOD, SIRT1, and FOXO3a reduced significantly (P<0...
November 20, 2017: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/29222408/brain-insulin-resistance-impairs-hippocampal-synaptic-plasticity-and-memory-by-increasing-glua1-palmitoylation-through-foxo3a
#15
Matteo Spinelli, Salvatore Fusco, Marco Mainardi, Federico Scala, Francesca Natale, Rosita Lapenta, Andrea Mattera, Marco Rinaudo, Domenica Donatella Li Puma, Cristian Ripoli, Alfonso Grassi, Marcello D'Ascenzo, Claudio Grassi
High-fat diet (HFD) and metabolic diseases cause detrimental effects on hippocampal synaptic plasticity, learning, and memory through molecular mechanisms still poorly understood. Here, we demonstrate that HFD increases palmitic acid deposition in the hippocampus and induces hippocampal insulin resistance leading to FoxO3a-mediated overexpression of the palmitoyltransferase zDHHC3. The excess of palmitic acid along with higher zDHHC3 levels causes hyper-palmitoylation of AMPA glutamate receptor subunit GluA1, hindering its activity-dependent trafficking to the plasma membrane...
December 8, 2017: Nature Communications
https://www.readbyqxmd.com/read/29211704/histone-deacetylase-hdac-inhibitor-suberoylanilide-hydroxamic-acid-saha-induces-apoptosis-in-prostate-cancer-cell-lines-via-the-akt-foxo3a-signaling-pathway
#16
Xuan-Yan Shi, Wei Ding, Tie-Qiu Li, Yi-Xiong Zhang, Shan-Chao Zhao
BACKGROUND Histone deacetylase (HDAC) inhibitors are emerging as a new class of anti-cancer drugs that promote cancer cell apoptosis, and include suberoylanilide hydroxamic acid (SAHA). The aim of this study was to investigate the mechanism of SAHA-induced apoptosis in human prostate cancer cell lines, DU145 and PC-3. MATERIAL AND METHODS Cell lines, DU145 and PC-3, were studied before and after treatment with SAHA. The effects of SAHA treatment on cell proliferation were studied using the MTT cell proliferation assay...
December 6, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29198881/role-of-arsenic-exposure-in-adipose-tissue-dysfunction-and-its-possible-implication-in-diabetes-pathophysiology
#17
REVIEW
Kaviyarasi Renu, Harishkumar Madhyastha, Radha Madhyastha, Masugi Maruyama, Sankarganesh Arunachlam, Abilash V G
Exposure to arsenic in drinking water can stimulate a diverse number of diseases that originate from impaired lipid metabolism in adipose and glucose metabolism, leading to insulin resistance. Arsenic inhibits differentiation of adipocyte and mediates insulin resistance with diminutive information on arsenicosis on lipid storage and lipolysis. This review focused on different mechanisms and pathways involved in adipogenesis and lipolysis in adipose tissue during arsenic-induced diabetes. Though arsenic is known to cause type2 diabetes through different mechanisms, the role of adipose tissue in causing type2 diabetes is still unclear...
December 1, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/29198702/hydrogen-protects-against-hyperoxia-induced-apoptosis-in-type-ii-alveolar-epithelial-cells-via-activation-of-pi3k-akt-foxo3a-signaling-pathway
#18
Dan Wu, Mulin Liang, Hongxing Dang, Fang Fang Feng Xu, Chengjun Liu
Oxidative stress is regarded as a key regulator in the pathogenesis of prolonged hyperoxia-induced lung injury, which causes injury to alveolar epithelial cells and eventually leads to development of bronchopulmonary dysplasia (BPD). Many studies have shown that hydrogen has a protective effect in a variety of cells. However, the mechanisms by which hydrogen rescues cells from damage due to oxidative stress in BPD remains to be fully elucidated. This study sought to evaluate the effects of hydrogen on hyperoxia-induced lung injury and to investigate the underlying mechanism...
November 30, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29157834/16-hydroxycleroda-3-13-dien-15-16-olide-inhibits-the-proliferation-and-induces-mitochondrial-dependent-apoptosis-through-akt-mtor-and-mek-erk-pathways-in-human-renal-carcinoma-cells
#19
Cheng Liu, Wei-Chang Lee, Bu-Miin Huang, Yi-Chen Chia, Yu-Chi Chen, Yung-Chia Chen
BACKGROUND: Renal cell carcinoma (RCC) is well known that it cannot be treated with traditional chemotherapy or radiotherapy. 16-Hydroxycleroda-3,13-dien-15,16-olide (CD), isolated from Polyalthia longifolia Benth. & Hook. f. var. pendula had been reported to display significant efficacy against cancer cell lines. PURPOSE: To determine the anti-tumour activities of CD in two clear cell type RCC (ccRCC) cell lines (A-498 and 786-O). In addition, the underlying mechanisms were also examined...
December 1, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/29157092/single-agent-and-synergistic-combinatorial-efficacy-of-first-in-class-small-molecule-imipridone-onc201-in-hematological-malignancies
#20
Varun V Prabhu, Mala K Talekar, Amriti R Lulla, C Leah B Kline, Lanlan Zhou, Junior Hall, A Pieter J Van den Heuvel, David T Dicker, Jawad Babar, Stephan A Grupp, Mathew J Garnett, Ultan McDermott, Cyril H Benes, Jeffrey J Pu, David F Claxton, Nadia Khan, Wolfgang Oster, Joshua E Allen, Wafik S El-Deiry
ONC201, founding member of the imipridone class of small molecules, is currently being evaluated in advancer cancer clinical trials. We explored single agent and combinatorial efficacy of ONC201 in preclinical models of hematological malignancies. ONC201 demonstrated (GI50 1-8 µM) dose- and time-dependent efficacy in acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myelogenous leukemia (CML), chronic lymphocytic leukemia (CLL), diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), Burkitt's lymphoma, anaplastic large cell lymphoma (ALCL), cutaneous T-cell lymphoma (CTCL), Hodgkin's lymphoma (nodular sclerosis) and multiple myeloma (MM) cell lines including cells resistant to standard of care (dexamethasone in MM) and primary samples...
November 20, 2017: Cell Cycle
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