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https://www.readbyqxmd.com/read/29334671/glucosamine-promotes-osteoblast-proliferation-by-modulating-autophagy-via-the-mammalian-target-of-rapamycin-pathway
#1
Chen Lv, Lu Wang, Xiongbai Zhu, Wenjun Lin, Xin Chen, Zhengxiang Huang, Lintuo Huang, Shengwu Yang
Glucosamine is effective in the treatment of osteoarthritis; however, its effect on osteoporosis remains unclear. Decreased activity of osteoblasts is the main cause of osteoporosis. Here, we examined the effects of glucosamine on osteoblasts. The potential underlying mechanisms were explored. The results showed that glucosamine had a biphasic effect on the viability of hFOB1.19 osteoblasts. At low concentrations (<0.6 mM), glucosamine induced hFOB1.19 cell proliferation, whereas at high concentrations (>0...
January 12, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29334602/high-dose-metformin-plus-temozolomide-shows-increased-anti-tumor-effects-in-glioblastoma-in-vitro-and-in-vivo-compared-with-monotherapy
#2
Jung Eun Lee, Ji Hee Lim, Yong Kil Hong, Seung Ho Yang
Purpose: The purpose of the study is to investigate the efficacy of combined treatment with temozolomide (TMZ) and metformin for glioblastoma (GBM) in vitro and in vivo. Materials and Methods: We investigated the efficacy of combined treatment with TMZ and metformin using cell viability and apoptosis assays. A GBM orthotopic mice model was established by inoculation of 5x105 U87 cells and treated with metformin, TMZ, and the combination for 4 weeks. Western blotting and immunofluorescence of tumor specimens were analyzed to investigate AMP-activated protein kinase (AMPK) and AKT pathway...
January 10, 2018: Cancer Research and Treatment: Official Journal of Korean Cancer Association
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/29331082/mechanistic-target-of-rapamycin-complex-1-and-2-in-human-temporal-lobe-epilepsy
#4
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/29330421/premature-recruitment-of-oocyte-pool-and-increased-mtor-activity-in-fmr1-knockout-mice-and-reversal-of-phenotype-with-rapamycin
#5
E Mok-Lin, M Ascano, A Serganov, Z Rosenwaks, T Tuschl, Z Williams
While mutations in the fragile X mental retardation-1 (FMR1) gene are associated with varying reproductive outcomes in females, the effects of a complete lack of FMR1 expression are not known. Here, we studied the ovarian and reproductive phenotypes in an Fmr1 knockout (KO) mouse model and the role of mammalian target of rapamycin (mTOR) signaling. Breeding, histologic and mTOR signaling data were obtained at multiple time points in KO and wild type (WT) mice fed a control or rapamycin (mTOR inhibitor) diet...
January 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29330362/dynamic-modelling-of-the-mtor-signalling-network-reveals-complex-emergent-behaviours-conferred-by-deptor
#6
Thawfeek M Varusai, Lan K Nguyen
The mechanistic Target of Rapamycin (mTOR) signalling network is an evolutionarily conserved network that controls key cellular processes, including cell growth and metabolism. Consisting of the major kinase complexes mTOR Complex 1 and 2 (mTORC1/2), the mTOR network harbours complex interactions and feedback loops. The DEP domain-containing mTOR-interacting protein (DEPTOR) was recently identified as an endogenous inhibitor of both mTORC1 and 2 through direct interactions, and is in turn degraded by mTORC1/2, adding an extra layer of complexity to the mTOR network...
January 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29330317/trna-production-links-nutrient-conditions-to-the-onset-of-sexual-differentiation-through-the-torc1-pathway
#7
Yoko Otsubo, Tomohiko Matsuo, Akiko Nishimura, Masayuki Yamamoto, Akira Yamashita
Target of rapamycin (TOR) kinase controls cell growth and metabolism in response to nutrient availability. In the fission yeast Schizosaccharomyces pombe, TOR complex 1 (TORC1) promotes vegetative growth and inhibits sexual differentiation in the presence of ample nutrients. Here, we report the isolation and characterization of mutants with similar phenotypes as TORC1 mutants, in that they initiate sexual differentiation even in nutrient-rich conditions. In most mutants identified, TORC1 activity is downregulated and the mutated genes are involved in tRNA expression or modification...
January 12, 2018: EMBO Reports
https://www.readbyqxmd.com/read/29330052/esco2-knockdown-inhibits-cell-proliferation-and-induces-apoptosis-in-human-gastric-cancer-cells
#8
Hongmei Chen, Lei Zhang, Wenting He, Liu Tao, Yang Zhao, Hao Chen, Yumin Li
Establishment of cohesion 1 homolog 2 (ESCO2), an essential gene for cohesion regulation and genomic stability, has not been studied in human gastric cancer (GC). We found that ESCO2 knockdown in human GC cell lines dramatically inhibited cell proliferation and induced cell apoptosis in vitro and suppressed tumor xenograft development in vivo. Furthermore, adenosine monophosphate-activated protein kinase (AMPK) was activated following the suppression of its downstream targets, including mammalian target of rapamycin (mTOR) and p70 ribosomal S6 kinase 1 (p70S6K1), and this result was consistent with p53 activation...
January 9, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29330011/mutations-in-pi3k110%C3%AE-cause-impaired-nk-cell-function-partially-rescued-by-rapamycin-treatment
#9
Raquel Ruiz-García, Alexander Vargas-Hernandez, Ivan K Chinn, Laura S Angelo, Tram N Cao, Zeynep Coban-Akdemir, Shalini N Jhangiani, Qingchang Meng, Lisa R Forbes, Donna M Muzny, Luis M Allende, Mohammed S Ehlayel, Richard A Gibbs, James R Lupski, Gulbu Uzel, Jordan S Orange, Emily M Mace
BACKGROUND: Heterozygous gain-of-function mutations in PI3K110 lead to lymphadenopathy, lymphoid hyperplasia, Epstein-Barr virus (EBV) and cytomegalovirus (CMV) viremia, and sinopulmonary infections. OBJECTIVE: The known role of NK cell function in the control of EBV and CMV prompted us to investigate the functional and phenotypic effect of PI3K110δ mutations on NK cell subsets and cytotoxic function. METHODS: Patient mutations were identified by whole exome or targeted sequencing...
January 9, 2018: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29329496/positive-feedback-regulation-of-subchondral-h-type-vessel-formation-by-chondrocyte-promotes-osteoarthritis-development-in-mice
#10
Jiansen Lu, Haiyan Zhang, Daozhang Cai, Chun Zeng, Pinglin Lai, Yan Shao, Hang Fang, Delong Li, Jiayao Ouyang, Chang Zhao, Denghui Xie, Bin Huang, Jian Yang, Yu Jiang, Xiaochun Bai
Vascular-invasion-mediated interactions between activated articular chondrocytes and subchondral bone are essential for osteoarthritis (OA) development. Here, we determined the role of nutrient sensing mechanistic target of rapamycin complex 1 (mTORC1) signaling in the crosstalk across the bone cartilage interface and its regulatory mechanisms. Then mice with chondrocyte-specific mTORC1 activation (Tsc1 CKO and Tsc1 CKOER ) or inhibition (Raptor CKOER ) and their littermate controls were subjected to OA induced by destabilization of the medial meniscus (DMM) or not...
January 12, 2018: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/29329306/lifespan-extension-without-fertility-reduction-following-dietary-addition-of-the-autophagy-activator-torin1-in-drosophila-melanogaster
#11
Janet S Mason, Tom Wileman, Tracey Chapman
Autophagy is a highly conserved mechanism for cellular repair that becomes progressively down-regulated during normal ageing. Hence, manipulations that activate autophagy could increase lifespan. Previous reports show that manipulations to the autophagy pathway can result in longevity extension in yeast, flies, worms and mammals. Under standard nutrition, autophagy is inhibited by the nutrient sensing kinase Target of Rapamycin (TOR). Therefore, manipulations of TOR that increase autophagy may offer a mechanism for extending lifespan...
2018: PloS One
https://www.readbyqxmd.com/read/29329237/mtor-pathways-in-cancer-and-autophagy
#12
REVIEW
Mathieu Paquette, Leeanna El-Houjeiri, Arnim Pause
TOR (target of rapamycin), an evolutionarily-conserved serine/threonine kinase, acts as a central regulator of cell growth, proliferation and survival in response to nutritional status, growth factor, and stress signals. It plays a crucial role in coordinating the balance between cell growth and cell death, depending on cellular conditions and needs. As such, TOR has been identified as a key modulator of autophagy for more than a decade, and several deregulations of this pathway have been implicated in a variety of pathological disorders, including cancer...
January 12, 2018: Cancers
https://www.readbyqxmd.com/read/29328494/pterostilbene-inhibits-reactive-oxygen-species-production-and-apoptosis-in-primary-spinal-cord-neurons-by-activating-autophagy-via-the-mechanistic-target-of-rapamycin-signaling-pathway
#13
Jing-Lan He, Xiao-Hui Dong, Zong-Hu Li, Xiao-Ying Wang, Zhi-An Fu, Na Shen
Autophagy is an important self-adaptive mechanism that is involved in inhibiting reactive oxygen species (ROS) in spinal cord neurons. Pterostilbene, a natural plant extract, has been demonstrated to possess antioxidant effects; however, it has not yet been investigated whether pterostilbene could activate autophagy and protect spinal cord neurons from oxidative stress. In the present study, primary spinal cord neurons of Sprague Dawley rats were cultured. Cell counting kit‑8 analysis was used to detect cytotoxicity of pterostilbene...
January 9, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29328465/effects-of-diphyllin-as-a-novel-v-atpase-inhibitor-on-te-1-and-eca-109-cells
#14
Haijiao Chen, Pengfei Liu, Ting Zhang, Yi Gao, Yingdi Zhang, Xiuyun Shen, Xiao Li, Weidong Shen
Diphyllin is a natural component of traditional Chinese medicine, which effectively inhibits V-ATPase activity and affects the progression of cancer. However, few studies have been conducted on esophageal cancer, and the mechanisms remain to be elucidated. The present study revealedthat diphyllin inhibited proliferation and induced S arrest in esophageal cancer cell lines TE-1 and ECA-109. Further experiments revealed that diphyllin inhibited V-ATPase activity and decreased the mRNA expression of mammalian target of rapamycin complex 1 (mTORC1), hypoxia-inducible factor-1α (HIF-1α), and vascular endothelial growth factor (VEGF)...
January 4, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29328424/vitexin-induces-g2-m%C3%A2-phase-arrest-and-apoptosis-via-akt-mtor-signaling-pathway-in-human-glioblastoma-cells
#15
Guangning Zhang, Dongyuan Li, Hao Chen, Junchen Zhang, Xingyi Jin
Glioblastoma is a common primary brain tumor with aggressive malignancy, which results in poor outcomes, short survival time and high mortality. Vitexin, an active ingredient from natural products, has been reported to inhibit cell growth and induce cell apoptosis in various cancer cell lines including hepatocellular carcinoma, oral and esophageal cancer. To the best of the authors knowledge, the present study was the first to investigate anticancer effects of vitexin on human glioblastoma cells and potential underlying mechanisms...
January 8, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29328421/antitumor-activity-of-curcumin-by-modulation-of-apoptosis-and-autophagy-in-human-lung-cancer-a549-cells-through-inhibiting-pi3k-akt-mtor-pathway
#16
Furong Liu, Song Gao, Yuxuan Yang, Xiaodan Zhao, Yameng Fan, Wenxia Ma, Danrong Yang, Aimin Yang, Yan Yu
Curcumin is known to exhibit anticancer effects on various cancers with selective cytotoxicity in tumor cells. In the present study, the effects of curcumin‑induced multiple PCDs on human non‑small cell lung cancer (NSCLC) cells and the potential molecular mechanisms of apoptosis and autophagy triggered by curcumin via the PI3K/Akt/mTOR signaling pathway were explored, further confirmed by co‑culture of curcumin with mTOR blocker rapamycin and PI3K/Akt inhibitor LY294002. The anti‑proliferation effect of different stimulus was measured by MTT assay...
January 4, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29328379/mir%C3%A2-1273g%C3%A2-3p-promotes-proliferation-migration-and-invasion-of-lovo-cells-via-cannabinoid-receptor-1-through-activation-of-erbb4-pik3r3-mtor-s6k2-signaling-pathway
#17
Min Li, Xiaoping Qian, Mingzhen Zhu, Aiyi Li, Mingzhi Fang, Yong Zhu, Jingyu Zhang
MicroRNAs (miR) are important in various crucial cell processes including proliferation, migration and invasion. Dysregulation of miRNAs have been increasingly reported to contribute to colorectal cancer. However, the detailed biological function and potential mechanisms of miR‑1273g‑3p in colorectal cancer remain poorly understood. The expression levels of miR‑1273g‑3p in human colorectal cancer LoVo cell lines were detected via reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR)...
January 9, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29327159/efficacy-and-safety-of-third-line-molecular-targeted-therapy-in-metastatic-renal-cell-carcinoma-resistant-to-first-line-vascular-endothelial-growth-factor-receptor-tyrosine-kinase-inhibitor-and-second-line-therapy
#18
Hiroki Ishihara, Toshio Takagi, Tsunenori Kondo, Hidekazu Tachibana, Kazuhiko Yoshida, Kenji Omae, Junpei Iizuka, Hirohito Kobayashi, Kazunari Tanabe
BACKGROUND: The number of studies evaluating the efficacy and safety of third-line molecular-targeted therapy for metastatic renal cell carcinoma (mRCC) is limited. METHODS: The data for 48 patients with disease progression after first-line vascular endothelial growth factor receptor tyrosine kinase inhibitor (TKI) and second-line targeted therapy were evaluated. Patients with prior cytokine therapy were excluded. Overall survival (OS) after first- and second-line therapy initiation was compared between patients with and without third-line therapy...
January 11, 2018: International Journal of Clinical Oncology
https://www.readbyqxmd.com/read/29326972/aggressive-neuroendocrine-tumor-of-the-ovary-with-multiple-metastases-treated-with-everolimus-a-case-report
#19
Michiko Kaiho-Sakuma, Masafumi Toyoshima, Mika Watanabe, Asami Toki, Satomi Kameda, Takamichi Minato, Hitoshi Niikura, Nobuo Yaegashi
•Neuroendocrine tumors (NETs) frequently occur in the lungs or the gastrointestinal tract; they are uncommon in the ovary.•The mammalian target of rapamycin (mTOR) pathway has been reported as a treatment for advanced NETs.•We describe a patient with an aggressive primary ovarian NET, successfully treated with everolimus (an mTOR inhibitor).
February 2018: Gynecologic Oncology Reports
https://www.readbyqxmd.com/read/29326164/the-glutamine-transporter-asct2-slc1a5-promotes-tumor-growth-independently-of-the-amino-acid-transporter-lat1-slc7a5
#20
Yann Cormerais, Pierre André Massard, Milica Vucetic, Sandy Giuliano, Eric Tambutté, Jerome Durivault, Valérie Vial, Hitoshi Endou, Michael F Wempe, Scott K Parks, Jacques Pouyssegur
The transporters for glutamine and essential amino acids (EAA), ASCT2 (solute carrier family 1 member 5, SLC1A5), and LAT1 (solute carrier family 7 member 5, SLC7A5), respectively are overexpressed in aggressive cancers and have been identified as cancer-promoting targets. Moreover, previous work has suggested that glutamine influx via ASCT2 triggers EAA entry via the LAT1 exchanger, thus activating mechanistic target of rapamycin complex 1 (mTORC1) and stimulating growth. Here, to further investigate whether these two transporters are functionally coupled, we compared the respective knockout (KO) of either LAT1 or ASCT2 in colon (LS174T) and lung (A549) adenocarcinoma cell lines...
January 11, 2018: Journal of Biological Chemistry
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