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https://www.readbyqxmd.com/read/28102849/berberine-sonodynamic-therapy-induces-autophagy-and-lipid-unloading-in-macrophage
#1
Jiayuan Y Kou, Ying Li, Zhaoyu Y Zhong, Yueqing Q Jiang, Xuesong S Li, Xiaobo B Han, Zhongni N Liu, Ye Tian, Liming M Yang
Impaired autophagy in macrophages accompanies the progression of atherosclerosis and contributes to lipid loading in plaques and ineffective lipid degradation. Therefore, evoking autophagy and its associated cholesterol efflux may provide a therapeutic treatment for atherosclerosis. In the present study, berberine-mediated sonodynamic therapy (BBR-SDT) was used to induce autophagy and cholesterol efflux in THP-1 macrophages and derived foam cells. Following BBR-SDT, autophagy was increased in the macrophages, autophagy resistance in the foam cells was prevented, and cholesterol efflux was induced...
January 19, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28102733/plk1-polo-like-kinase-1-inhibits-mtor-complex-1-and-promotes-autophagy
#2
Stefanie Ruf, Alexander Martin Heberle, Miriam Langelaar-Makkinje, Sara Gelino, Deepti Wilkinson, Carolin Gerbeth, Jennifer Jasmin Schwarz, Birgit Holzwarth, Bettina Warscheid, Chris Meisinger, Marcel A T M van Vugt, Ralf Baumeister, Malene Hansen, Kathrin Thedieck
Mechanistic target of rapamycin complex 1 (MTORC1) and PLK1 (polo like kinase 1) are major drivers of cancer cell growth and proliferation, and inhibitors of both protein kinases are currently being investigated in clinical studies. To date, MTORC1's and PLK1's functions are mostly studied separately, and reports on their mutual crosstalk are scarce. Here, we identify PLK1 as a physical MTORC1 interactor in human cancer cells. PLK1 inhibition enhances MTORC1 activity under nutrient sufficiency and in starved cells, and PLK1 directly phosphorylates the MTORC1 component RPTOR/RAPTOR in vitro...
January 19, 2017: Autophagy
https://www.readbyqxmd.com/read/28101526/rapamycin-resistant-mtor-activity-is-required-for-sensory-axon-regeneration-induced-by-a-conditioning-lesion
#3
Weitao Chen, Na Lu, Yue Ding, Yuan Wang, Leung Ting Chan, Xu Wang, Xin Gao, Songshan Jiang, Kai Liu
Neuronal mammalian target of rapamycin (mTOR) activity is a critical determinant of the intrinsic regenerative ability of mature neurons in the adult central nervous system (CNS). However, whether its action also applies to peripheral nervous system (PNS) neurons after injury remains elusive. To address this issue unambiguously, we used genetic approaches to determine the role of mTOR signaling in sensory axon regeneration in mice. We showed that deleting mTOR in dorsal root ganglion (DRG) neurons suppressed the axon regeneration induced by conditioning lesions...
November 2016: ENeuro
https://www.readbyqxmd.com/read/28101248/expression-of-cancerous-inhibitor-of-protein-phosphatase-2a-in-human-triple-negative-breast-cancer-correlates-with-tumor-survival-invasion-and-autophagy
#4
Shan Li, Ting-Ting Feng, Yang Guo, Xianjun Yu, Qiuyue Huang, Liang Zhang, Wei Tang, Ying Liu
Cancerous inhibitor of protein phosphatase 2A (CIP2A) is a recently characterized oncoprotein which is involved in the progression of several human malignancies. The present study aimed to investigate its biological function in human triple negative breast cancer (TNBC). The expression of CIP2A in TNBC cells was examined and it was observed that CIP2A was elevated in the TNBC cell line compared with poorly invasive breast cancer cells. CIP2A depletion in TNBC cell lines inhibited proliferation, and induced apoptosis and autophagy...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28101201/diosmetin-inhibits-cell-proliferation-and-induces-apoptosis-by-regulating-autophagy-via-the-mammalian-target-of-rapamycin-pathway-in-hepatocellular-carcinoma-hepg2-cells
#5
Jie Liu, Hao Ren, Bin Liu, Qingyu Zhang, Mingyi Li, Runzhi Zhu
Hepatocellular carcinoma (HCC), which is a type of malignant tumor, is the fifth most common cancer in men and ninth in women worldwide. The aim of the present study was to investigate the antitumor effect of diosmetin (DIOS) in hepatocellular carcinoma HepG2 cells. The proliferation, apoptosis and autophagy rates of HepG2 cells were measured following treatment with DIOS. The effects of DIOS treatment on HepG2 cell proliferation and apoptosis rates were analyzed using MTT assays and Annexin V staining, respectively...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28100332/-expression-and-significance-of-mtor-4ebp1-hif-1%C3%AE-vegf-signaling-pathway-in-lung-tissues-of-asthmatic-mice
#6
Li Wang, Yan-Li Zhang, Xiu-Fang Wang, Zhe Song, Wei Wang
OBJECTIVE: To study the expression and significance of the mammalian target of rapamycin (mTOR)/eukaryote initiating factor 4E binding protein 1(4EBP1)/hypoxia inducible factor-1α (HIF-1α)/vascular endothelial growth factor (VEGF) signaling pathway in asthmatic mice. METHODS: Forty SPF level 6-8 week-old female Balb/C mice were randomly divided into control, asthma, budesonide and mTOR inhibitor (rapamycin) intervention groups (n=10 each). The asthmatic mouse model was prepared via OVA induction and challenge test...
January 2017: Zhongguo Dang Dai Er Ke za Zhi, Chinese Journal of Contemporary Pediatrics
https://www.readbyqxmd.com/read/28098858/mir-345-inhibits-tumor-metastasis-and-emt-by-targeting-irf1-mediated-mtor-stat3-akt-pathway-in-hepatocellular-carcinoma
#7
Miao Yu, Huanzhou Xue, Yadong Wang, Quan Shen, Qingfeng Jiang, Xiao Zhang, Ke Li, Meng Jia, Jiangkun Jia, Jian Xu, Yuwei Tian
MicroRNAs (miRNAs) have been reported to play critical roles in tumor progression including hepatocellular carcinoma (HCC). Thus, the underlying mechanisms need further investigation. Previous study reported that loss of miR-345 expression indicated a poor prognosis of HCC patients. This study evaluated whether loss of miR-345 could promote the tumor metastasis and epithelial-mesenchymal-transition (EMT) of HCC by targeting interferon regulatory factor 1 (IRF1)-mediated mTOR/STAT3/AKT signaling. Underexpression of miR-345 was identified in 65 cases of human HCC compared to matched tumor-adjacent tissues by qRT-PCR...
January 17, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28096940/the-next-10-years-challenges-for-the-future-and-overcoming-resistance-to-targeted-therapies-for-renal-cell-carcinoma
#8
REVIEW
Daniel Y C Heng
The introduction of targeted therapies over the past 10 years revolutionized the treatment of metastatic renal cell carcinoma (mRCC). The next 10 years hold promise for even greater expansion of the therapeutic armamentarium for mRCC. A number of recently completed and ongoing trials have explored the use of antivascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs) and mammalian target of rapamycin (mTOR) inhibitors in the adjuvant setting, the use of predictive biomarkers to guide personalized medicine, as well as new systemic treatments and combination therapies for mRCC...
November 2016: Canadian Urological Association Journal, Journal de L'Association des Urologues du Canada
https://www.readbyqxmd.com/read/28096282/the-effect-of-mtor-inhibitors-on-respiratory-infections-in-lymphangioleiomyomatosis
#9
REVIEW
Andrew M Courtwright, Hilary J Goldberg, Elizabeth Petri Henske, Souheil El-Chemaly
Lymphangioleiomyomatosis (LAM) is a destructive cystic lung disease. Mammalian target of rapamycin (mTOR) inhibitors are the primary treatment for LAM but it is unknown whether these immunosuppressing medications increase the risk for or the severity of respiratory infections in LAM patients.We searched multiple databases for original articles that reported the rate of respiratory infections in LAM patients treated with mTOR inhibitors or placebo. We calculated incidence rates for respiratory infections in these groups and incidence rate ratios for respiratory infections and severe respiratory infections in mTOR inhibitors treated versus placebo treated patients...
January 2017: European Respiratory Review: An Official Journal of the European Respiratory Society
https://www.readbyqxmd.com/read/28094770/rapamycin-mediated-mtor-inhibition-uncouples-hiv-1-latency-reversal-from-cytokine-associated-toxicity
#10
Alyssa R Martin, Ross A Pollack, Adam Capoferri, Richard F Ambinder, Christine M Durand, Robert F Siliciano
Current strategies for HIV-1 eradication require the reactivation of latent HIV-1 in resting CD4+ T cells (rCD4s). Global T cell activation is a well-characterized means of inducing HIV-1 transcription, but is considered too toxic for clinical applications. Here, we have explored a strategy that involves a combination of immune activation and the immunosuppressive mTOR inhibitor rapamycin. In purified rCD4s from HIV-1-infected individuals on antiretroviral therapy, rapamycin treatment downregulated markers of toxicity, including proinflammatory cytokine release and cellular proliferation that were induced after potent T cell activation using αCD3/αCD28 antibodies...
January 17, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28093061/polyphyllin-ii-restores-sensitization-of-the-resistance-of-pc-9-zd-cells-to-gefitinib-by-a-negative-regulation-of-the-pi3k-akt-mtor-signaling-pathway
#11
Ruzhen Zheng, Hao Jiang, Jinhui Li, Xinge Liu, Hongwei Xu
: EGFR tyrosine kinase inhibitors (TKIs) are widely used for advanced non-small cell lung cancer (NSCLC) patients with a sensitizing EGFR mutation and provide a promising treatment strategy. However, acquired resistance to EGFR-TKIs restrict their application. The mechanisms underlying acquired resistance to TKIs have been explored and Phosphoinositide 3-kinase (PI3K)/Akt/mTOR pathway plays a very important role in NSCLC development as well as EGFR-TKI resistance. Polyphyllin II(PP II) is the main steroidal saponin constituent which derives from the root of Paris polychylia...
December 13, 2016: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28092822/combination-of-everolimus-with-sorafenib-for-solid-renal-tumors-in-tsc2-mice-is-superior-to-everolimus-alone
#12
Jian Yang, Paulina A Samsel, Kalin Narov, Ashley Jones, Daniel Gallacher, John Gallacher, Julian R Sampson, Ming Hong Shen
Tuberous sclerosis (TSC) is an inherited tumor syndrome caused by mutations in TSC1 or TSC2 that lead to aberrant activation of mTOR and development of tumors in multiple organs including the kidneys. The mTOR inhibitors rapamycin and everolimus (rapalogs) have demonstrated clinical efficacy in treating TSC-associated tumors including renal angiomyolipomas. However, tumor responses are usually only partial, and regrowth occurs after drug withdrawal. TSC-associated tumors are highly vascular, and TSC patients with renal angiomyolipomas have elevated levels of circulating vascular endothelial growth factor (VEGF) A and VEGFD...
January 13, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28092744/quercetin-induces-apoptosis-and-autophagy-in-primary-effusion-lymphoma-cells-by-inhibiting-pi3k-akt-mtor-and-stat3-signaling-pathways
#13
Marisa Granato, Celeste Rizzello, Maria Saveria Gilardini Montani, Laura Cuomo, Marina Vitillo, Roberta Santarelli, Roberta Gonnella, Gabriella D'Orazi, Alberto Faggioni, Mara Cirone
Quercetin, a bioflavonoid contained in several vegetables daily consumed, has been studied for long time for its antiinflammatory and anticancer properties. Quercetin interacts with multiple cancer-related pathways such as PI3K/AKT, Wnt/β-catenin and STAT3. These pathways are hyperactivated in primary effusion lymphoma (PEL), an aggressive B cell lymphoma whose pathogenesis is strictly linked to the oncogenic virus Kaposis' Sarcoma-associated Herpesvirus (KSHV). In this study, we found that quercetin inhibited PI3K/AKT/mTOR and STAT3 pathways in PEL cells, and as a consequence, it down-regulated the expression of the prosurvival cellular proteins such as c-FLIP, cyclin D1 and cMyc...
January 5, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28092667/oncogenic-braf-fusions-in-mucosal-melanomas-activate-the-mapk-pathway-and-are-sensitive-to-mek-pi3k-inhibition-or-mek-cdk4-6-inhibition
#14
H S Kim, M Jung, H N Kang, H Kim, C-W Park, S-M Kim, S J Shin, S H Kim, S G Kim, E K Kim, M R Yun, Z Zheng, K Y Chung, J Greenbowe, S M Ali, T-M Kim, B C Cho
Despite remarkable progress in cutaneous melanoma genomic profiling, the mutational landscape of primary mucosal melanomas (PMM) remains unclear. Forty-six PMMs underwent targeted exome sequencing of 111 cancer-associated genes. Seventy-six somatic nonsynonymous mutations in 42 genes were observed, and recurrent mutations were noted on eight genes, including TP53 (13%), NRAS (13%), SNX31 (9%), NF1 (9%), KIT (7%) and APC (7%). Mitogen-activated protein kinase (MAPK; 37%), cell cycle (20%) and phosphatidylinositol 3-kinase (PI3K)-mTOR (15%) pathways were frequently mutated...
January 16, 2017: Oncogene
https://www.readbyqxmd.com/read/28092463/ccaat-enhancer-binding-protein-%C3%AE-mediates-the-killing-of-toxoplasma-gondii-by-inducing-autophagy-in-nonhematopoietic-cells
#15
Yanhui Yu, Na Zhao, Jiaqi An, Xichen Zhang
Autophagy is a main defense strategy by which infected host cells can virtually induce the killing of parasite, including Toxoplasma gondii. However, the regulatory mechanisms of autophagy in T. gondii-infected nonhematopoietic cells are still unknown. Emerging evidence indicates that CCAAT/enhancer-binding protein β (C/EBP β) is associated with the regulation of autophagy. Herein, we hypothesized that C/EBP β plays roles in inducing autophagy in nonhematopoietic cells. Expression of C/EBP β was aberrantly regulated in endothelial cells and retinal pigment epithelial cells challenged by T...
January 16, 2017: DNA and Cell Biology
https://www.readbyqxmd.com/read/28089725/high-concentration-of-branched-chain-amino-acids-promotes-oxidative-stress-inflammation-and-migration-of-human-peripheral-blood-mononuclear-cells-via-mtorc1-activation
#16
Olha Zhenyukh, Esther Civantos, Marta Ruiz-Ortega, Maria Soledad Sánchez, Clotilde Vázquez, Concepción Peiró, Jesús Egido, Sebastián Mas
Leucine, isoleucine and valine are essential aminoacids termed branched-chain amino acids (BCAA) due to its aliphatic side-chain. In several pathological and physiological conditions increased BCAA plasma concentrations have been described. Elevated BCAA levels predict insulin resistance development. Moreover, BCAA levels higher than 2mmol/L are neurotoxic by inducing microglial activation in maple syrup urine disease. However, there are no studies about the direct effects of BCAA in circulating cells. We have explored whether BCAA could promote oxidative stress and pro-inflammatory status in peripheral blood mononuclear cells (PBMCs) obtained from healthy donors...
January 13, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28089416/strategies-to-overcome-therapeutic-resistance-in-renal-cell-carcinoma
#17
REVIEW
Peter J Siska, Kathryn E Beckermann, W Kimryn Rathmell, Scott M Haake
BACKGROUND: Renal cell cancer (RCC) is a prevalent and lethal disease. At time of diagnosis, most patients present with localized disease. For these patients, the standard of care includes nephrectomy with close monitoring thereafter. While many patients will be cured, 5-year recurrence rates range from 30% to 60%. Furthermore, nearly one-third of patients present with metastatic disease at time of diagnosis. Metastatic disease is rarely curable and typically lethal. Cytotoxic chemotherapy and radiation alone are incapable of controlling the disease...
January 11, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/28089247/-mid-gut-neuroendocrine-tumors-news-on-medical-treatment
#18
Marie Dior, Johann Dreanic, Caroline Prieux-Klotz, Bertrand Brieau, Catherine Brezault, Romain Coriat
CONTEXT: Mid gut neuroendocrine tumors (NET) are rare tumors whose incidence is increasing. Curative surgery remains the gold standard for the treatment of NETs of the small intestine. Surgery should be considered as soon as possible even if a metastatic stage is diagnosed. The management of unresectable well-differentiated metastatic NETs of the small intestine recently changed with the publication of trials demonstrating the benefit of targeted therapies and metabolic radiotherapy, leading to a change of practices and update of French and international recommendations...
January 11, 2017: La Presse Médicale
https://www.readbyqxmd.com/read/28088782/pde5-inhibitors-enhance-the-lethality-of-pemetrexed-sorafenib
#19
Laurence Booth, Jane L Roberts, Andrew Poklepovic, Paul Dent
The combination of pemetrexed and sorafenib has significant clinical activity against a wide variety of tumor types in patients and the present studies were performed to determine whether sildenafil enhances the killing potential of [pemetrexed + sorafenib]. In multiple genetically diverse lung cancer cell lines, sildenafil enhanced the lethality of [pemetrexed + sorafenib]. The three-drug combination reduced the activities of AKT, mTOR and STAT transcription factors; increased the activities of eIF2α and ULK-1; lowered the expression of MCL-1, BCL-XL, thioredoxin and SOD2; and increased the expression of Beclin1...
January 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28088315/paris-saponin-induced-autophagy-promotes-breast-cancer-cell-apoptosis-via-the-akt-mtor-signaling-pathway
#20
Zhan-Zhi Xie, Man-Mei Li, Peng-Fei Deng, Sheng Wang, Lei Wang, Xue-Ping Lu, Liu-Bing Hu, Zui Chen, Hui-Yang Jie, Yi-Fei Wang, Xiao-Xiao Liu, Zhong Liu
Paris saponins possess anticancer, anti-inflammatory, and antiviral effects. However, the anticancer effect of Paris saponins has not been well elucidated and the mechanisms underlying the potential function of Paris saponins in cancer therapy are needed to be further identify. In this study, we report that saponin compounds isolated from Paris polyphylla exhibited antitumor activity against breast cancer cell lines, MCF-7 and MDA-MB-231. Paris saponin XA-2 induced apoptosis in both cell lines, as evidenced by the activation of caspases and cleavage of Poly (ADP-ribose) polymerase...
January 11, 2017: Chemico-biological Interactions
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