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mtor protein, human

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https://www.readbyqxmd.com/read/28715695/new-liver-cancer-biomarkers-pi3k-akt-mtor-pathway-members-and-eukaryotic-translation-initiation-factors
#1
Nicole Golob-Schwarzl, Stefanie Krassnig, Anna M Toeglhofer, Young Nyun Park, Margit Gogg-Kamerer, Klemens Vierlinger, Fabian Schröder, Hyungjn Rhee, Rudolf Schicho, Peter Fickert, Johannes Haybaeck
Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide. The initiation of protein translation is an important rate-limiting step in eukaryotes and is crucial in many viral infections. Eukaryotic translation initiation factors (eIFs) are involved in the initiation step of protein translation and are linked to the phosphatidylinositol-3-kinases PI3K/AKT/mTOR pathway. Therefore we aimed to investigate a potential role of eIFs in HCC. We herein report on the immunohistochemical expression of the various eIF subunits in 235 cases of virus-related human HCC...
July 14, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28714804/cellular-proliferation-and-differentiation-induced-by-single-layer-molybdenum-disulfide-and-mediation-mechanisms-of-proteins-via-the-akt-mtor-p70s6k-signaling-pathway
#2
Wei Zou, Xingli Zhang, Mengyang Zhao, Qixing Zhou, Xiangang Hu
Single-layer molybdenum disulfide (SLMoS2) is a novel kind of 2D nanosheet that has attracted great attention regarding its use in biosensors, drug delivery, tissue engineering and therapy. However, our results demonstrated that SLMoS2 accelerated proliferation and promoted myogenic differentiation and epithelial-mesenchymal transition (EMT) in human embryonic lung fibroblasts (HELFs). The abnormal proliferation and differentiation of HELFs contribute to idiopathic pulmonary fibrosis. Specifically, SLMoS2 significantly stimulated the expression of myofibroblast- and mesenchymal-associated genes and proteins...
July 17, 2017: Nanotoxicology
https://www.readbyqxmd.com/read/28713965/dihydroartemisinin-and-gefitinib-synergistically-inhibit-nsclc-cell-growth-and-promote-apoptosis-via-the-akt-mtor-stat3-pathway
#3
Hong Jin, Ai-Ying Jiang, Han Wang, Yong Cao, Yan Wu, Xiao-Feng Jiang
Non‑small cell lung cancer (NSCLC) is among the leading causes of cancer‑associated mortality worldwide. In clinical practice, therapeutic strategies based on drug combinations are often used for the treatment of various types of cancer. The present study aimed to investigate the effects of the combination of dihydroartemisinin (DHA) and gefitinib on NSCLC. Cell Counting kit 8 assay was used to evaluate cell viability. Transwell assays were performed to investigate cellular migration and invasion, and cellular apoptosis was evaluated using the terminal deoxynucleotidyl transferase dUTP nick‑end labeling assay...
July 14, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28713919/ganetespib-induces-g2-m-cell-cycle-arrest-and-apoptosis-in-gastric-cancer-cells-through-targeting-of-receptor-tyrosine-kinase-signaling
#4
Harry Lee, Nipun Saini, Amanda B Parris, Ming Zhao, Xiaohe Yang
Heat shock protein 90 (HSP90) regulates several important cellular processes via its repertoire of 'client proteins'. These client proteins have been found to play fundamental roles in signal transduction, cell proliferation, cell cycle progression and survival, as well as other features of malignant cells, such as invasion, tumor angiogenesis and metastasis. Thus, HSP90 is an emerging target for cancer therapy. To this end, we evaluated ganetespib (STA-9090), a novel and potent HSP90 inhibitor, for its activity in gastric cancer cell lines...
July 13, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28713020/pneumolysin-induced-autophagy-contributes-to-inhibition-of-osteoblast-differentiation-through-downregulation-of-sp1-in-human-osteosarcoma-cells
#5
Jinwook Kim, Hee-Weon Lee, Dong Kwon Rhee, James C Paton, Suhkneung Pyo
BACKGROUND INFORMATION: The 53kDa protein pneumolysin (PLY) is the main virulence factor of Streptococcus pneumoniae, a leading cause of invasive pneumococcal diseases. PLY forms pores in cholesterol-containing membranes, thereby interfering with the function of cells. Bone destruction is a serious matter in chronic inflammatory diseases such as septic arthritis and osteomyelitis. S. pneumoniae is increasingly being recognized as a common cause of septic arthritis, but its pathogenesis is poorly defined...
July 13, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28712846/reactive-astrocytes-promote-als-like-degeneration-and-intracellular-protein-aggregation-in-human-motor-neurons-by-disrupting-autophagy-through-tgf-%C3%AE-1
#6
Pratibha Tripathi, Natalia Rodriguez-Muela, Joseph R Klim, A Sophie de Boer, Sahil Agrawal, Jackson Sandoe, Claudia S Lopes, Karolyn Sassi Ogliari, Luis A Williams, Matthew Shear, Lee L Rubin, Kevin Eggan, Qiao Zhou
Amyotrophic lateral sclerosis (ALS) is a fatal and rapidly progressing motor neuron disease. Astrocytic factors are known to contribute to motor neuron degeneration and death in ALS. However, the role of astrocyte in promoting motor neuron protein aggregation, a disease hallmark of ALS, remains largely unclear. Here, using culture models of human motor neurons and primary astrocytes of different genotypes (wild-type or SOD1 mutant) and reactive states (non-reactive or reactive), we show that reactive astrocytes, regardless of their genotypes, reduce motor neuron health and lead to moderate neuronal loss...
June 29, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28711913/silencing-protein-kinase-c-%C3%AE-by-microrna-25-5p-activates-ampk-signaling-and-inhibits-colorectal-cancer-cell-proliferation
#7
Shihu Zhang, Yiyang Zhang, Qing Cheng, Zhaoqun Ma, Guanwen Gong, Zhengming Deng, Kun Xu, Gaoyuan Wang, Yousong Wei, Xiaoping Zou
Developing novel strategies against human colorectal cancer (CRC) cells is needed. Activation of AMP-activated protein kinase (AMPK) could possibly inhibit CRC cells. Protein kinase C ζ (PKCζ) is an AMPK negative regulator. Here we found that PKCζ expression was significantly elevated in human colon cancer tissues and CRC cells. PKCζ upregulation was correlated with AMPK in-activation and mTOR complex 1 (mTORC1) over-activation. Reversely, PKCζ shRNA knockdown activated AMPK signaling and inhibited HT-29 cell proliferation...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28710377/antiangiogenic-activity-of-phthalides-enriched-angelica-sinensis-extract-by-suppressing-wsb-1-pvhl-hif-1%C3%AE-vegf-signaling-in-bladder-cancer
#8
Meng-Chuan Chen, Wen-Lin Hsu, Wen-Liang Chang, Tz-Chong Chou
The hypoxia-inducible factor-1α (HIF-1α) plays a critical role in tumor angiogenesis. It has been reported that the acetone extract of Angelica sinensis (AE-AS) rich in phthalides is able to inhibit cancer cell proliferation. However, whether AE-AS reduces cancer angiogenesis remains unknown. In this study, we demonstrated that AE-AS significantly inhibited the angiogenesis in vitro and in vivo evidenced by attenuation of the tube formation in hypoxic human umbilical vascular endothelial cells (HUVECs), and the vasculature generation in Matrigel plug, the chicken chorioallantoic membrane, and tumors...
July 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28708103/pharmacogenomics-of-targeted-agents-for-personalization-of-colorectal-cancer-treatment
#9
REVIEW
Alessia Bignucolo, Elena De Mattia, Erika Cecchin, Rossana Roncato, Giuseppe Toffoli
The use of targeted agents in the treatment of metastatic colorectal cancer (CRC) has improved patient outcomes. Anti-epidermal growth factor receptor (anti-EGFR) agents (cetuximab and panitumumab) and antiangiogenic molecules (bevacizumab, regorafeninb, ramucirumab, and aflibercept) have been successfully integrated into clinical practice. Other drugs have been designed to target additional deregulated pathways in CRC, such as MAPK (mitogen-activated protein kinase)/PI3K-AKT (phosphatidylinositol-3-kinase-AKT serine/threonine kinase)/mTOR (mammalian target of rapamycin), HER-2 and 3 ( human epidermal growth factor receptor-2 and -3), and BRAF...
July 14, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28705212/moringa-isothiocyanate-complexed-with-%C3%AE-cyclodextrin-a-new-perspective-in-neuroblastoma-treatment
#10
Sabrina Giacoppo, Renato Iori, Patrick Rollin, Placido Bramanti, Emanuela Mazzon
BACKGROUND: Several lines of evidence suggest the consume of natural products for cancer prevention or treatment. In particular, isothiocyanates (ITCs) exerting anti-cancer properties, have received great interest as potential chemotherapeutic agents. This study was designed to assess the anti-proliferative activities of a new preparation of Moringa oleifera-derived 4-(α-L-rhamnopyranosyloxy)benzyl ITC (moringin) complexed with alpha-cyclodextrin (moringin + α-CD; MAC) on SH-SY5Y human neuroblastoma cells...
July 14, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28703800/killing-two-birds-with-one-stone-dual-blockade-of-integrin-and-fgf-signaling-through-targeting-syndecan-4-in-postoperative-capsular-opacification
#11
Yingyan Qin, Yi Zhu, Furong Luo, Chuan Chen, Xiaoyun Chen, Mingxing Wu
The most common complication after cataract surgery is postoperative capsular opacification, which includes anterior capsular opacification (ACO) and posterior capsular opacification (PCO). Increased adhesion of lens epithelial cells (LECs) to the intraocular lens material surface promotes ACO formation, whereas proliferation and migration of LECs to the posterior capsule lead to the development of PCO. Cell adhesion is mainly mediated by the binding of integrin to extracellular matrix proteins, while cell proliferation and migration are regulated by fibroblast growth factor (FGF)...
July 13, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28701921/endothelial-monocyte-activating-polypeptide-ii-suppresses-the-in-vitro-glioblastoma-induced-angiogenesis-by-inducing-autophagy
#12
Zhiqing Li, Jun Ma, Libo Liu, Xiaobai Liu, Ping Wang, Yunhui Liu, Zhen Li, Jian Zheng, Jiajia Chen, Wei Tao, Yixue Xue
The obstacle in delivering therapeutics to glioblastoma (GBM) is tumor-induced angiogenesis which leads to the formation of abnormal vessels and a dysfunctional blood-tumor barrier. Here, we elucidated the effect of endothelial-monocyte activating polypeptide II (EMAP II) on the GBM-induced angiogenesis as well as its potential mechanisms. Our results proved that EMAP II inhibited the viability, mitochondrial membrane potential, migration and tube formation of GBM-induced endothelial cells (GECs) by inducing cell autophagy, demonstrated by cell viability assay, JC-1 staining assay, transwell assay and tube formation assay, respectively...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28700668/conditional-cell-reprogramming-involves-non-canonical-%C3%AE-catenin-activation-and-mtor-mediated-inactivation-of-akt
#13
Frank A Suprynowicz, Christopher M Kamonjoh, Ewa Krawczyk, Seema Agarwal, Anton Wellstein, Fadeke A Agboke, Sujata Choudhury, Xuefeng Liu, Richard Schlegel
The combination of irradiated fibroblast feeder cells and Rho kinase inhibitor, Y-267362, converts primary epithelial cells growing in vitro into an undifferentiated adult stem cell-like state that is characterized by long-term proliferation. This cell culture method also maintains the proliferation of adult epithelial stem cells from various tissues. Both primary and adult stem cells retain their tissue-specific differentiation potential upon removal of the culture conditions. Due to the ability to modulate the proliferation and differentiation of the cells, this method is referred to as conditional reprogramming and it is increasingly being used in studies of tumor heterogeneity, personalized medicine and regenerative medicine...
2017: PloS One
https://www.readbyqxmd.com/read/28699918/ampk-activation-dependent-autophagy-compromises-oleanolic-acid-induced-cytotoxicity-in-human-bladder-cancer-cells
#14
Yarong Song, Peng Zhang, Yadong Sun, Xuechao Li, Lifeng Chen, Yajun Xiao, Yifei Xing
Autophagy is an evolutionarily conserved catabolic process in eukaryotic cells, which allows cells to overcome a wide array of of stresses and has recently been shown to result in drug resistance. This study examined the effect of autophagy on oleanolic acid (OA)-induced cytotoxicity against bladder cancer cells. Our study demonstrated that OA inhibited cell viability, proliferation, and induced apoptosis in bladder cancer lines T24 and EJ. Furthermore, OA induced autophagy in both cell lines by activating AMP-activated protein kinase (AMPK), inhibiting mechanistic target of rapamycin (mTOR) and promoting unc-51 like autophagy activating kinase 1 (ULK1)...
July 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28695747/novel-strategies-for-anti-aging-drug-discovery
#15
Komal Saraswat, Syed Ibrahim Rizvi
Scientific achievements in the last few decades, leading to effective therapeutic interventions, have dramatically improved human life expectancy. Consequently, aging has become a significant problem and represents the major risk factor for most human pathologies including diabetes, cardiovascular diseases, neurological disorders, and cancer. Scientific discoveries over the past two decades have been instrumental in dissecting molecular mechanism(s) which play important roles in determining longevity. The same understanding has also led to the acknowledgement of the plurality of 'causes' which act either alone or in combination to create the condition which can be defined as 'aging'...
July 11, 2017: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/28694664/mir-382-functions-as-a-tumor-suppressor-against-esophageal-squamous-cell-carcinoma
#16
Jie Feng, Bo Qi, Ling Guo, Ling-Yun Chen, Xiu-Feng Wei, Yu-Zhen Liu, Bao-Sheng Zhao
AIM: To explore the effect of miR-382 on esophageal squamous cell carcinoma (ESCC) in vitro and its possible molecular mechanism. METHODS: Eca109 cells derived from human ESCC and Het-1A cells derived from human normal esophageal epithelium were used. Lentivirus-mediated miR-382 was overexpressed in Eca109 cells. The effect of miR-382 on cell proliferation was evaluated by MTT and colony formation assay. For cell cycle analysis, cells were fixed and stained for 30 min with propidium iodide (PI) staining buffer containing 10 mg/mL PI and 100 mg/mL RNase A, and analyzed by BD FACSCalibur™ flow cytometer...
June 21, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28694500/resistance-exercise-initiates-mechanistic-target-of-rapamycin-mtor-translocation-and-protein-complex-co-localisation-in-human-skeletal-muscle
#17
Zhe Song, Daniel R Moore, Nathan Hodson, Carl Ward, Jessica R Dent, Mary F O'Leary, Andrew M Shaw, D Lee Hamilton, Sovan Sarkar, Yann-Gaël Gangloff, Troy A Hornberger, Lawrence L Spriet, George J Heigenhauser, Andrew Philp
The mechanistic target of rapamycin (mTOR) is a central mediator of protein synthesis in skeletal muscle. We utilized immunofluorescence approaches to study mTOR cellular distribution and protein-protein co-localisation in human skeletal muscle in the basal state as well as immediately, 1 and 3 h after an acute bout of resistance exercise in a fed (FED; 20 g Protein/40 g carbohydrate/1 g fat) or energy-free control (CON) state. mTOR and the lysosomal protein LAMP2 were highly co-localised in basal samples...
July 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28694456/single-cell-transcriptomics-of-east-asian-pancreatic-islets-cells
#18
Rajkumar Dorajoo, Yusuf Ali, Vanessa S Y Tay, Jonathan Kang, Sudhagar Samydurai, Jianjun Liu, Bernhard O Boehm
Single-cell RNA-seq (scRNA-seq) of pancreatic islets have reported on α- and β-cell gene expression in mice and subjects of predominantly European ancestry. We aimed to assess these findings in East-Asian islet-cells. 448 islet-cells were captured from three East-Asian non-diabetic subjects for scRNA-seq. Hierarchical clustering using pancreatic cell lineage genes was used to assign cells into cell-types. Differentially expressed transcripts between α- and β-cells were detected using ANOVA and in silico replications of mouse and human islet cell genes were performed...
July 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28694352/protease-activated-receptor-2-promotes-kidney-tubular-epithelial-inflammation-by-inhibiting-autophagy-via-the-pi3k-akt-mtor-signalling-pathway
#19
Chunyang Du, Tao Zhang, Xia Xiao, Yonghong Shi, Huijun Duan, Yunzhuo Ren
Protease activated receptors 2 (PAR2), which belongs to a specific class of the G-protein-coupled receptors, are central to several inflammation processes. However, the precise molecular mechanism involved remains undefined. Autophagy has been previously shown to affect inflammation. In this study, we examine the effect of PAR2 on kidney tubular epithelial autophagy and on autophagy-related inflammation and reveal the underlying mechanism involved. Autophagic activity and levels of autophagic marker LC3 were examined in human kidney tubular epithelial cells with PAR2 knockdown or overexpression...
July 10, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28693262/axin1-protects-against-testicular-germ-cell-tumors-via-the-pi3k-akt-mtor-signaling-pathway
#20
Hailiang Xu, Yunyun Feng, Zhankui Jia, Jinjian Yang, Xueren Lu, Jun Li, Mingliang Xia, Chunru Wu, Yonggang Zhang, Jianhua Chen
Axis inhibition protein 1 (AXIN1) is characterized as a tumor suppressor in numerous types of cancer. However, the functional role of AXIN1 in the testicular germ cell tumors (TGCTs) remains unclear. The human embryonal carcinoma-derived cell line NTera2 was transfected with a recombinant AXIN1 expression vector (pcDNA3.1-AXIN1) and/or a small interfering RNA (siRNA) directed against AXIN1 (siAXIN). Following transfection, the mRNA and protein levels of AXIN1 were determined via reverse transcription-quantitative polymerase chain reaction analysis and western blotting, respectively...
July 2017: Oncology Letters
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