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https://www.readbyqxmd.com/read/29334302/mirnas-as-potential-regulators-of-mtor-pathway-in-renal-cell-carcinoma
#1
Inês Nogueira, Francisca Dias, Ana Luísa Teixeira, Rui Medeiros
Renal cell carcinoma (RCC) is the most commonly occurring solid cancer of the adult kidney with the majority of RCC cases being detected accidentally. The most aggressive subtype is clear cell RCC (ccRCC). miRNAs, a family of small noncoding RNAs regulating gene expression have been identified as key biological modulators. The von Hippel-Lindau pathway is one of the signaling pathways involved in the pathophysiology of ccRCC. Another oncogenic mechanism involves the activation of PI3K/AKT/mTOR signaling and serves as a central regulator of cell metabolism, proliferation and survival...
January 15, 2018: Pharmacogenomics
https://www.readbyqxmd.com/read/29334272/extracellular-vesicle-mimetic-nanovesicles-transport-lncrna-h19-as-competing-endogenous-rna-for-the-treatment-of-diabetic-wounds
#2
Shi-Cong Tao, Bi-Yu Rui, Qi-Yang Wang, Ding Zhou, Yang Zhang, Shang-Chun Guo
Diabetic wounds, one of the most enervating complications of diabetes mellitus, affect millions of people worldwide annually. Vascular insufficiency, caused by hyperglycemia, is one of the primary causes and categories of diabetic impaired wound healing. Recently, long noncoding RNA (LncRNA)-H19, which is significantly decreased in diabetes and may be crucial in triggering angiogenesis, has attracted increasing interest. The possible relationship between the decrease of LncRNA-H19 and the impairment of angiogenesis in diabetes could involve impairment of the insulin-phosphatidylinositol 3-kinase (PI3K)-Akt pathway via the interdiction of LncRNA-H19...
November 2018: Drug Delivery
https://www.readbyqxmd.com/read/29333385/kaempferol-inhibits-angiogenesis-by-suppressing-hif-1%C3%AE-and-vegfr2-activation-via-erk-p38-mapk-and-pi3k-akt-mtor-signaling-pathways-in-endothelial-cells
#3
Gi Dae Kim
Kaempferol has been shown to inhibit vascular formation in endothelial cells. However, the underlying mechanisms are not fully understood. In the present study, we evaluated whether kaempferol exerts antiangiogenic effects by targeting extracellular signal-regulated kinase (ERK)/p38 mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K)/Akt/mechanistic target of rapamycin (mTOR) signaling pathways in endothelial cells. Endothelial cells were treated with various concentrations of kaempferol for 24 h...
December 2017: Preventive Nutrition and Food Science
https://www.readbyqxmd.com/read/29332342/study-on-the-association-between-pi3k-akt-mtor-signaling-pathway-gene-polymorphism-and-susceptibility-to-gastric-cancer
#4
Lei Qi, Kewen Sun, Yun Zhuang, Jing Yang, Jianping Chen
PURPOSE: Excessive activation of PI3K/AKT/mTOR signaling pathway is one of the most common changes in human cancers, and single nucleotide polymorphisms (SNPs) existing in its functional region can affect the occurrence process of a variety of cancers. This study aimed to screen out the SNPs associated with susceptibility to gastric cancer in the PI3K/AKT/mT0R signaling pathway. METHODS: In this case-control study, the tagging SNPs in the promoter region5'-UTR, exon region or 3'-UTR of PIK3CA, PIK3CB, PIK3R1, PIK3R2, PIK3R3, AKT1, AKT2, AKT3 and mTOR genes were screened out...
November 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/29332340/imperatorin-shows-selective-antitumor-effects-in-sgc-7901-human-gastric-adenocarcinoma-cells-by-inducing-apoptosis-cell-cycle-arrest-and-targeting-pi3k-akt-m-tor-signalling-pathway
#5
J U Am, W J Gong, Y Su, Z B Mou
PURPOSE: The main purpose of the present study was to determine the anticancer properties of imperatorin - a naturally occurring coumarin compound - against SGC-7901 human gastric adenocarcinoma cells and the mouse fibroblast cell line 3T3 (normal cell line). METHODS: Imperatorin effects on apoptosis induction, cell cycle phase distribution and PI3K/Akt/m-TOR signalling pathways were studied. MTT cell viability assay examined the compound's cytotoxic potential, while inverted phase contrast microscopy and fluorescence microscopy techniques were used to study morphological changes induced in SGC-7901 cells by imperatorin...
November 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/29331856/schizandrin-a-enhances-chemosensitivity-of-colon-carcinoma-cells-to-5-fluorouracil-through-up-regulation-of-mir-195
#6
Dongfang Kong, Deyong Zhang, Xianqun Chu, Jing Wang
Nowadays 5-fluorouracil (5-FU)-based adjuvant chemotherapy is widely used for treating colon carcinoma. However, 5-FU resistance in the treatment of colon carcinoma has become more common and thereby new therapeutic strategies and new adjuvant drugs still need to be explored. Two 5-FU-resistant colon cancer cell lines, HCT116 and SW480, were used to investigate the effects of Schizandrin A (SchA), 5-FU, or their combination on cell viability and apoptosis. Besides, the role of miR-195 was studied to further clarify the specific function of SchA...
January 11, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29331805/synthesis-characterization-and-anticancer-activity-in%C3%A2-vitro-and-in%C3%A2-vivo-evaluation-of-an-iridium-iii-polypyridyl-complex
#7
Qiao-Yan Yi, Dan Wan, Bing Tang, Yang-Jie Wang, Wen-Yao Zhang, Fan Du, Miao He, Yun-Jun Liu
An iridium (III) complex [Ir(ppy)2(BDPIP)]PF6 (Ir-1) was reported to show high anticancer activity and may be used as a potent anticancer drug. In the current study, we designed and synthesized a novel iridium (III) complex and evaluated its potential inhibitory effect on the cancer cell growth in vitro and in vivo. This complex was found to display high cytotoxic activity in vitro and in vivo against A549 cell with a low IC50 value of 3.6 ± 0.3 μM and inhibiting percentage of tumor growth is 63.84% compared with the control...
December 1, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29331753/an-iridium-iii-complex-as-potent-anticancer-agent-induces-apoptosis-and-autophagy-in-b16%C3%A2-cells-through-inhibition-of-the-akt-mtor-pathway
#8
Bing Tang, Dan Wan, Yang-Jie Wang, Qiao-Yan Yi, Bo-Hong Guo, Yun-Jun Liu
A new ligand THPDP (THPDP = 11-(6,7,8,9-tetrahydrophenazin-2-yl)dipyrido[3,2-a:2',3'-c]phenazine) and its iridium(III) complex [Ir(ppy)2(THPDP)]PF6 (Ir-1) was synthesized and characterized by elemental analysis, IR, ESI-MS, 1H NMR and 13C NMR. The cytotoxicity in vitro of the complex against cancer cells B16, A549, Eca-109, SGC-7901, BEL-7402 and normal NIH 3T3 cell lines was evaluated using MTT method. The IC50 values of the complex toward B16, A549 and Eca-109 cells are 1.0 ± 0.02, 1.4 ± 0...
December 30, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29331751/comprehensive-genomic-profiling-of-head-and-neck-squamous-cell-carcinoma-reveals-fgfr1-amplifications-and-tumour-genomic-alterations-burden-as-prognostic-biomarkers-of-survival
#9
C Dubot, V Bernard, M P Sablin, S Vacher, W Chemlali, A Schnitzler, G Pierron, K Ait Rais, N Bessoltane, E Jeannot, J Klijanienko, O Mariani, T Jouffroy, V Calugaru, C Hoffmann, M Lesnik, N Badois, F Berger, C Le Tourneau, M Kamal, I Bieche
BACKGROUND: We aimed at identifying deleterious genomic alterations from untreated head and neck squamous cell carcinoma (HNSCC) patients, and assessing their prognostic value. PATIENTS AND METHODS: We retrieved 122 HNSCC patients who underwent primary surgery. Targeted NGS was used to analyse a panel of 100 genes selected among the most frequently altered genes in HNSCC and potential therapeutic targets. We selected only deleterious (activating or inactivating) single nucleotide variations, and copy number variations for analysis...
January 10, 2018: European Journal of Cancer
https://www.readbyqxmd.com/read/29331388/e4bp4-inhibits-angii-induced-apoptosis-in-h9c2-cardiomyoblasts-by-activating-the-pi3k-akt-pathway-and-promoting-calcium-uptake
#10
Bih-Cheng Chen, Marthandam Asokan Shibu, Chia-Hua Kuo, Chia-Yao Shen, Shu Nu Chang-Lee, Chao-Hung Lai, Ray-Jade Chen, Chun-Hsu Yao, Vijaya Padma Viswanadha, Jian-Shen Liu, Wei-Kung Chen, Chih-Yang Huang
The bZIP transcription factor E4BP4 is a survival factor that is known to be elevated in diseased heart and promote cell survival. In this study the role of E4BP4 on angiotensin-II (AngII)-induced apoptosis has been examined in in vitro cell model. H9c2 cardiomyoblast cells that overexpressed E4BP4 were exposed to AngII to observe the cardio-protective effects of E4BP4 on hypertension related apoptosis. The results from TUNEL assays revealed that E4BP4 significantly attenuated AngII-induced apoptosis. Further analysis by Western blot and RT-PCR showed that E4BP4 inhibited AngII-induced IGF-II mRNA expression and cleavage of caspase-3 through the PI3K-Akt pathway...
January 10, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/29331082/mechanistic-target-of-rapamycin-complex-1-and-2-in-human-temporal-lobe-epilepsy
#11
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/29330844/bradykinin-mediates-the-association-of-collecting-duct-cells-to-form-migratory-colonies-through-b2-receptor-activation
#12
Edith Del Valle Guaytima, Yamila Romina Brandán, Nicolás Octavio Favale, Bruno Jaime Santacreu, Norma B Sterin-Speziale, María Gabriela Márquez
It is known that bradykinin (BK) B2 receptor (B2R) is expressed in the collecting duct (CD) cells of the newborn rat kidney, but little is known about its role during early postnatal life. Therefore, we hypothesize that BK could participate in the mechanisms that mediate CD formation during the postnatal renal development. Performing primary cultures, combined with biochemical, immunocytochemical, and time-lapse analysis, we studied the role of BK in CD cell behaviour isolated from renal papilla of neonatal rats...
January 13, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29330743/acute-downregulation-of-mir-155-leads-to-a-reduced-collagen-synthesis-through-attenuating-macrophages-inflammatory-factor-secretion-by-targeting-ship1
#13
Longlong Yang, Lingying Liu, Huinan Ying, Yonghui Yu, Donghai Zhang, Huping Deng, Haijun Zhang, Jiake Chai
Fibrosis, tightly associated with fibroblasts collagen synthesis, is related closely with inflammatory response. Our previously study found that acute downregulation of miR-155 at wound sites leads to a reduced fibrosis, however its particular mechanism is unclear. Herein, we aimed to explore the mechanism of miR-155 in reducing fibrosis. We first found that down-regulation of miR-155 inhibited macrophages transforming growth factor-β1 (TGF-β1) and IL-1β secretion. Next, we found that co-cultured with macrophages increased the proliferation and collagen synthesis of fibroblasts, and downregulation of miR-155 in macrophages could effectively attenuate the accelerative effects...
January 12, 2018: Journal of Molecular Histology
https://www.readbyqxmd.com/read/29330287/targeted-akt-inhibition-in-prostate-cancer-cells-and-spheroids-reduces-aerobic-glycolysis-and-generation-of-hyperpolarized-1-13c-lactate
#14
Sui Seng Tee, Izabela Suster, Steven Truong, Sangmoo Jeong, Roozbeh Eskandari, Valentina Di Gialleonardo, Julio A Alvarez, Hannah N Aldeborgh, Kayvan Keshari
The PI3K/AKT/mTOR (PAM) signaling pathway is frequently mutated in prostate cancer. Specific AKT inhibitors are now in advanced clinical trials and this study investigates the effect of MK2206, a non-ATP competitive inhibitor, on the cellular metabolism in the context of prostate cancer. A significant reduction in cell motility and aerobic glycolysis was observed in prostate cancer cells with treatment. These changes were not accompanied by a reduction in the ratio of high-energy phosphates or a change in total protein levels of enzymes (e...
January 12, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29330285/foxo-dependent-par-4-upregulation-prevents-long-term-survival-of-residual-cells-following-pi3k-akt-inhibition
#15
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/29330129/estradiol-up-regulates-l-type-ca2-channels-via-membrane-bound-estrogen-receptor-phosphoinositide-3kinase-akt-camp-response-element-binding-protein-signaling-pathway
#16
Xiaoyan Yang, Xiaofang Mao, Gao Xu, Shasha Xing, Ansuman Chattopadhyay, Si Jin, Guy Salama
BACKGROUND: In long QT type-2 (LQT2), women are more prone to lethal arrhythmias called Torsade de Pointes (TdP) than men. We previously reported that 17-β-estradiol (E2) upregulates L-type Ca2+-channels and current (ICa,L) (∼30%) in rabbit ventricular myocytes by a classical genomic-mechanism mediated by estrogen-receptor-α (ER)α. In LQT2 ( IKr-blockade or bradycardia), the higher Ca2+ influx via ICa,L, causes Ca2+-overload, spontaneous sarcoplasmic reticulum Ca2+-release, and re-activation of ICa,L that trigger early afterdepolarizations (EADs) and TdP...
January 9, 2018: Heart Rhythm: the Official Journal of the Heart Rhythm Society
https://www.readbyqxmd.com/read/29329609/garcinia-xanthochymus-extract-protects-pc12-cells-from-h2o2-induced-apoptosis-through-modulation-of-pi3k-akt-and-nrf2-ho-1-pathways
#17
Jing Xu, Sheng Gan, Jun Li, De-Bing Wand, Yu Chen, Xin Hu, Guang-Zhong Yang
The aim of the present study was to investigate the protective effects and underlying mechanisms of Garcinia xanthochymus, a perennial medicinal plant native to Yunnan, China, against H2O2-induced oxidative damage in rat pheochromacytoma PC12 cells. Preincubation of PC12 cells with fruit EtOAc fraction (fruit-EFr., 12.5-50 µmol·L-1) of G. xanthochymus for 24 h prior to H2O2 exposure markedly improved cell viability and increased the activities of antioxidant enzymes (superoxide dismutase, catalase, and heme oxygenase-1 [HO-1]), prevented lactate dehydrogenase release and lipid peroxidation malondialdehyde production, attenuated the decrease of matrix metalloproteinases (MMP), and scavenged reactive oxygen species (ROS)...
November 2017: Chinese Journal of Natural Medicines
https://www.readbyqxmd.com/read/29329415/establishment-of-a-three-dimensional-model-to-study-human-uterine-angiogenesis
#18
Camille L Duran, Colette A Abbey, Kayla J Bayless
STUDY QUESTION: Can primary human uterine microvascular endothelial cells (UtMVECs) be used as a model to study uterine angiogenic responses in vitro that are relevant in pregnancy? SUMMARY ANSWER: UtMVECs demonstrated angiogenic responses when stimulated with proangiogenic factors, including sphingosine 1-phosphate (S1P), vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), physiological levels of wall shear stress (WSS), human chorionic gonadotropin (hCG) and various combinations of estrogen and progesterone...
December 21, 2017: Molecular Human Reproduction
https://www.readbyqxmd.com/read/29328863/overexpression-of-mtor-and-p-240-244-s6-in-idh1-wild-type-human-glioblastomas-is-predictive-of-low-survival
#19
Luis Eduardo Machado, Arthur William Alvarenga, Fernanda Ferreira da Silva, Martín Roffé, Maria Dirlei Begnami, Luís Fernando Bleggi Torres, Isabela Werneck da Cunha, Vilma Regina Martins, Glaucia Noeli Maroso Hajj
PI3K/Akt/mTOR pathway activation is a hallmark of high-grade gliomas, which prompted clinical trials for the use of PI3K and mTOR inhibitors. However, the poor results in the original trials suggested that better patient profiling was needed for such drugs. Thus, accurate and reproducible monitoring of mTOR complexes can lead to improved therapeutic strategies. In this work, we evaluated the expression and phosphorylation of mTOR, RAPTOR, and rpS6 in 195 human astrocytomas and 30 normal brain tissue samples...
January 1, 2018: Journal of Histochemistry and Cytochemistry: Official Journal of the Histochemistry Society
https://www.readbyqxmd.com/read/29328793/novel-molecular-and-phenotypic-insights-into-congenital-lung-malformations
#20
Daniel T Swarr, William H Peranteau, Jennifer Pogoriler, David B Frank, N Scott Adzick, Holly L Hedrick, Mike Morley, Su Zhou, Edward E Morrisey
RATIONALE: Disruption of normal pulmonary development is a leading cause of morbidity and mortality in infants. Congenital lung malformations are a unique model to study the molecular pathogenesis of isolated structural birth defects as they are often surgically resected. OBJECTIVES: To provide insight into the molecular pathogenesis of congenital lung malformations through analysis of cell-type and gene expression changes in these lesions. METHODS: Clinical data, and lung tissue for DNA, RNA, and histology were obtained from 58 infants undergoing surgical resection of a congenital lung lesion...
January 12, 2018: American Journal of Respiratory and Critical Care Medicine
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