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target of rapamycin

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https://www.readbyqxmd.com/read/29775813/hyaluronate-lactoferrin-layer-by-layer-coated-lipid-nanocarriers-for-targeted-co-delivery-of-rapamycin-and-berberine-to-lung-carcinoma
#1
Dalia M Kabary, Maged W Helmy, Kadria A Elkhodairy, Jia-You Fang, Ahmed O Elzoghby
The self-tumor targeting polymers, lactoferrin (LF) and hyaluronic acid (HA) were utilized to develop layer-by-layer (LbL) lipid nanoparticles (NPs) for dual delivery of berberine (BER) and rapamycin (RAP) to lung cancer. To control its release from the NPs, BER was hydrophobically ion paired with SLS prior to incorporation into NPs. Spherical HA/LF-LbL-RAP-BER/SLS-NPs 250.5 nm in diameter, with a surface charge of -18.5 mV were successfully elaborated. The NPs exhibited sequential release pattern with faster release of BER followed by controlled release of RAP which enables sensitization of lung tumor cells to the anti-cancer action of RAP...
May 15, 2018: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/29774169/phase-2-study-of-everolimus-for-relapsed-or-refractory-classical-hodgkin-lymphoma
#2
Patrick B Johnston, Lauren C Pinter-Brown, Ghulam Warsi, Kristen White, Radhakrishnan Ramchandren
Background: The current standard of care for classical Hodgkin lymphoma (HL) is multiagent chemotherapy with or without radiation. In patients who relapse or fail to respond, additional high-dose chemotherapy with autologous hematopoietic stem cell transplantation (AHSCT) can improve progression-free survival (PFS). Novel therapies are required for patients refractory to chemotherapy and AHSCT. The mammalian target of rapamycin inhibitor everolimus has shown preliminary activity in preclinical models of HL and promising efficacy in patients with relapsed or refractory HL...
2018: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/29772672/mtor-signaling-and-neural-stem-cells-the-tuberous-sclerosis-complex-model
#3
REVIEW
Alice Polchi, Alessandro Magini, Danila Di Meo, Brunella Tancini, Carla Emiliani
The mechanistic target of rapamycin (mTOR), a serine-threonine kinase, plays a pivotal role in regulating cell growth and proliferation. Notably, a great deal of evidence indicates that mTOR signaling is also crucial in controlling proliferation and differentiation of several stem cell compartments. Consequently, dysregulation of the mTOR pathway is often associated with a variety of disease, such as cancer and metabolic and genetic disorders. For instance, hyperactivation of mTORC1 in neural stem cells (NSCs) is associated with the insurgence of neurological manifestation characterizing tuberous sclerosis complex (TSC)...
May 16, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29772587/anti-inflammatory-effects-of-cardamonin-in-ovarian-cancer-cells-are-mediated-via-mtor-suppression
#4
Huajiao Chen, Daohua Shi, Peiguang Niu, Yanting Zhu, Jintuo Zhou
Cardamonin exhibits a variety of pharmacological activities including anti-inflammatory and antitumor, which are correlated with the inhibition of nuclear factor-kappaB and the mammalian target of rapamycin, respectively. However, whether the anti-inflammatory effects of cardamonin are mediated by the mammalian target of rapamycin remains unknown. In this study, ovarian cancer SKOV3 cells were cultured with lipopolysaccharide to induce inflammation, and the inhibitory effects and underlying molecular mechanisms of cardamonin were investigated using specific inhibitors of the mammalian target of rapamycin and the nuclear factor-kappaB pathway (rapamycin and pyrrolidine dithiocarbamate, respectively)...
May 17, 2018: Planta Medica
https://www.readbyqxmd.com/read/29770442/current-concepts-in-the-neuropathogenesis-of-mucolipidosis-type-iv
#5
REVIEW
Lauren C Boudewyn, Steven U Walkley
Mucolipidosis type IV (MLIV) is an autosomal recessive, lysosomal storage disorder causing progressively severe intellectual disability, motor and speech deficits, retinal degeneration often culminating in blindness, and systemic disease causing a shortened lifespan. MLIV results from mutations in the gene MCOLN1 encoding the transient receptor potential channel mucolipin-1. It is an ultra-rare disease and is currently known to affect just over 100 diagnosed individuals. The last decade has provided a wealth of research focused on understanding the role of the enigmatic mucolipin-1 protein in cell and brain function and how its absence causes disease...
May 16, 2018: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29770198/recent-advances-in-managing-understanding-meningioma
#6
REVIEW
Nawal Shaikh, Karan Dixit, Jeffrey Raizer
Meningiomas are the most common adult primary intracranial tumor. Despite their higher incidence, there have not-until recently-been as many advances in understanding and managing meningiomas. Thus far, two broad classes of meningiomas have emerged on the basis of their mutational profile: those driven by neurofibromatosis 2 (NF2) inactivation and those with non-NF2 driver gene alterations, such as mammalian target of rapamycin and Hedgehog, Wingless/b-catenin, Notch, transforming growth factor-b receptor, mitogen-activated protein kinase, and phospholipase C pathway alterations...
2018: F1000Research
https://www.readbyqxmd.com/read/29769719/klhl22-activates-amino-acid-dependent-mtorc1-signalling-to-promote-tumorigenesis-and-ageing
#7
Jie Chen, Yuhui Ou, Yanyan Yang, Wen Li, Ye Xu, Yuntao Xie, Ying Liu
The mechanistic target of rapamycin complex 1 (mTORC1) is a master regulator of cell growth that responds to a diverse set of environmental cues, including amino acids1,2 . Deregulation of mTORC1 has been linked with metabolic diseases, cancer and ageing2-4 . In response to amino acids, mTORC1 is recruited by the Rag GTPases to the lysosome, its site of activation5,6 . The GATOR1 complex, consisting of DEPDC5, NPRL3 and NPRL2, displays GAP activity to inactivate Rag GTPases under amino-acid-deficient conditions 7 ...
May 16, 2018: Nature
https://www.readbyqxmd.com/read/29768191/loss-of-a-negative-regulator-of-mtorc1-induces-aerobic-glycolysis-and-altered-fiber-composition-in-skeletal-muscle
#8
Paul A Dutchak, Sandi J Estill-Terpack, Abigail A Plec, Xiaozheng Zhao, Chendong Yang, Jun Chen, Bookyung Ko, Ralph J Deberardinis, Yonghao Yu, Benjamin P Tu
The conserved GATOR1 complex consisting of NPRL2-NPRL3-DEPDC5 inhibits mammalian target of rapamycin complex 1 (mTORC1) in response to amino acid insufficiency. Here, we show that loss of NPRL2 and GATOR1 function in skeletal muscle causes constitutive activation of mTORC1 signaling in the fed and fasted states. Muscle fibers of NPRL2 knockout animals are significantly larger and show altered fiber-type composition, with more fast-twitch glycolytic and fewer slow-twitch oxidative fibers. NPRL2 muscle knockout mice also have altered running behavior and enhanced glucose tolerance...
May 15, 2018: Cell Reports
https://www.readbyqxmd.com/read/29768134/mtor-signalling-jack-of-all-trades
#9
Yassine El Hiani, Emmanuel E Egom, Xian-Ping Dong
The mechanistic target of rapamycin (mTOR) is an evolutionarily conserved serine/threonine kinase that senses and integrates environmental information into cellular regulation and homeostasis. Accumulating evidence has suggested a master role of mTOR signaling in many fundamental aspects of cell biology and organismal development. mTOR deregulation is implicated in a broad range of pathological conditions, including diabetes, cancer, neurodegenerative diseases, myopathies, inflammatory, infectious and autoimmune conditions...
May 16, 2018: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
https://www.readbyqxmd.com/read/29766561/erythema-nodosum-arising-during-everolimus-therapy-for-tuberous-sclerosis-complex
#10
Eloise R Galligan, Lindsey Fix, Laura E Levin, Lisa Imundo, Darrell J Yamashiro, Maria C Garzon
Indications for everolimus and other drugs within the mammalian target of rapamycin inhibitor class have recently expanded to include tuberous sclerosis complex. Everolimus is generally well tolerated, but it is important for physicians to identify and manage associated cutaneous adverse effects. We report the first case of a child developing erythema nodosum while undergoing everolimus therapy.
May 16, 2018: Pediatric Dermatology
https://www.readbyqxmd.com/read/29766046/deletion-of-tsc2-in-nociceptors-reduces-target-innervation-ion-channel-expression-and-sensitivity-to-heat
#11
Dan Carlin, Judith P Golden, Amit Mogha, Vijay K Samineni, Kelly R Monk, Robert W Gereau, Valeria Cavalli
The mechanistic target of rapamycin complex 1 (mTORC1) is known to regulate cellular growth pathways, and its genetic activation is sufficient to enhance regenerative axon growth following injury to the central or peripheral nervous systems. However, excess mTORC1 activation may promote innervation defects, and mTORC1 activity mediates injury-induced hypersensitivity, reducing enthusiasm for the pathway as a therapeutic target. While mTORC1 activity is required for full expression of some pain modalities, the effects of pathway activation on nociceptor phenotypes and sensory behaviors are currently unknown...
March 2018: ENeuro
https://www.readbyqxmd.com/read/29765173/hemodiafiltration-and-plasma-levels-of-axitinib-in-a-patient-with-metastatic-renal-clear-cell-carcinoma
#12
Jindrich Kopecky, Alena Ticha, Hana Janeckova, Melichar Bohuslav
BACKGROUND: The standard treatment for metastatic renal cancer is based on vascular endothelial growth factor (VEGF) and mammalian target of rapamycin (mTor) inhibitors. Compared to other advanced tumors, the treatment of renal cancer is highly affected by impaired renal function; therefore, patients with severe renal insufficiency, including patients on hemodialysis, are generally excluded from clinical trials. CASE REPORT: In the present manuscript we present the case of a renal cancer patient who underwent bilateral nephrectomy and received two lines of treatment...
May 15, 2018: Biomedical Papers of the Medical Faculty of the University Palacký, Olomouc, Czechoslovakia
https://www.readbyqxmd.com/read/29764973/a-complex-mtor-response-in-habituation-paradigms-for-a-social-signal-in-adult-songbirds
#13
Somayeh Ahmadiantehrani, Elisa O Gores, Sarah E London
Nonassociative learning is considered simple because it depends on presentation of a single stimulus, but it likely reflects complex molecular signaling. To advance understanding of the molecular mechanisms of one form of nonassociative learning, habituation, for ethologically relevant signals we examined song recognition learning in adult zebra finches. These colonial songbirds learn the unique song of individuals, which helps establish and maintain mate and other social bonds, and informs appropriate behavioral interactions with specific birds...
June 2018: Learning & Memory
https://www.readbyqxmd.com/read/29763880/anti-neuroinflammatory-effects-of-20c-from-gastrodia-elata-via-regulating-autophagy-in-lps-activated-bv-2-cells-through-mapks-and-tlr4-akt-mtor-signaling-pathways
#14
Qian-Hang Shao, Xiao-Ling Zhang, Ying Chen, Cheng-Gen Zhu, Jian-Gong Shi, Yu-He Yuan, Nai-Hong Chen
20C, a novel bibenzyl compound, is isolated from Gastrodia elata. In our previous study, 20C showed protective effects on tunicamycin-induced endoplasmic reticulum stress, rotenone-induced apoptosis and rotenone-induced oxidative damage. However, the anti-neuroinflammatory effect of 20C is still with limited acquaintance. The objective of this study was to confirm the anti-neuroinflammatory effect of 20C on Lipopolysaccharide (LPS)-activated BV-2 cells and further elucidated the underlying molecular mechanisms...
May 12, 2018: Molecular Immunology
https://www.readbyqxmd.com/read/29762821/the-influencing-mechanism-of-mtor-signal-pathway-mediated-by-mitofusin-2-in-development-of-follicle
#15
Q-Y Luo, P Huo, L-L Wang, X-H Wu
OBJECTIVE: To investigate the influencing mechanism of mammalian target of rapamycin (mTOR) signal pathway mediated by mitofusin-2 (Mfn2) in the development of follicle. MATERIALS AND METHODS: We selected 20 healthy Sprague Dawley (SD) female rats aging between 6 and 8 weeks were divided into the control group and the polycystic ovarian syndrome (PCOS) model group. Rats in PCOS group received the lavage using 0.4 mL 1% carboxymethyl cellulose solution containing letrozole (1 mg/kg/d) consecutively for 20 to 25d...
April 2018: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29762750/the-apoptosis-in-arsenic-induced-oxidative-stress-is-associated-with-autophagy-in-the-testis-tissues-of-chicken
#16
Y Z Shao, H J Zhao, Y Wang, J J Liu, J L Li, L Y Luo, M W Xing
The aim of this study is to investigate whether arsenic (As) could induce testicular poisoning and influence the oxidative stress, apoptosis and autophagy in chickens. Seventy-two 1-day-old male Hy-line chickens were divided into 4 groups which were exposed to 0, 0.625, 1.25, and 2.5 mg/kg body weight (BW) of arsenic trioxide (As2O3) for 30, 60 and 90 days, respectively. Histological and ultrastructural changes, antioxidant enzyme activity, mRNA and protein levels of apoptosis and autophagy-related genes were detected...
May 14, 2018: Poultry Science
https://www.readbyqxmd.com/read/29761560/mtor-mediated-inactivation-of-4e-bp1-an-inhibitor-of-translation-precedes-cartilage-degeneration-in-rat-osteoarthritic-knees
#17
Olga Katsara, Victoria Kolupaeva
Proper control of protein synthesis is vital for tissue homeostasis and its deregulation is characteristic of many disorders including osteoarthritis (OA). The objectives of this work were to analyze and correlate changes in activity of the translation apparatus associated with cartilage degeneration in an animal model of OA. Osteoarthritis was induced surgically in rats by anterior cruciate ligament transection (ACLT). Using a modified Mankin scoring system and analysis of protein expression we demonstrated, that mechanistic target of rapamycin complex 1 (mTORC1)-mediated 4E-BP1 phosphorylation was detected significantly earlier than other mTORC1-mediated modifications, such as p70S6K and ULK1 phosphorylation...
May 14, 2018: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
https://www.readbyqxmd.com/read/29761287/activation-of-the-mtorc1-pathway-by-inflammation-contributes-to-vascular-calcification-in-patients-with-end-stage-renal-disease
#18
Jing Liu, Wei Zhu, Chun Ming Jiang, Yuan Feng, Yang Yang Xia, Qing Yan Zhang, Miao Zhang
BACKGROUND: Chronic inflammation plays an important role in the progression of vascular calcification (VC). This study was designed to explore the effects and underlying mechanisms of inflammation on VC in the radial arteries of patients with end-stage renal disease (ESRD) with arteriovenostomy. METHODS: Forty-eight ESRD patients were divided into control (n = 25) and inflammation groups (n = 23) according to plasma C-reactive protein (CRP) level. Surgically removed tissues from the radial arteries of patients receiving arteriovenostomy were used in this study...
May 14, 2018: Journal of Nephrology
https://www.readbyqxmd.com/read/29761115/depdc5-knockdown-causes-mtor-dependent-motor-hyperactivity-in-zebrafish
#19
Hortense de Calbiac, Adriana Dabacan, Elise Marsan, Hervé Tostivint, Gabrielle Devienne, Saeko Ishida, Eric Leguern, Stéphanie Baulac, Raul C Muresan, Edor Kabashi, Sorana Ciura
Objective: DEPDC5 was identified as a major genetic cause of focal epilepsy with deleterious mutations found in a wide range of inherited forms of focal epilepsy, associated with malformation of cortical development in certain cases. Identification of frameshift, truncation, and deletion mutations implicates haploinsufficiency of DEPDC5 in the etiology of focal epilepsy. DEPDC5 is a component of the GATOR1 complex, acting as a negative regulator of mTOR signaling. Methods: Zebrafish represents a vertebrate model suitable for genetic analysis and drug screening in epilepsy-related disorders...
May 2018: Annals of Clinical and Translational Neurology
https://www.readbyqxmd.com/read/29760955/nvp-bez235-a-dual-pi3k-mtor-inhibitor-suppresses-the-growth-of-fadu-hypopharyngeal-squamous-cell-carcinoma-and-has-a-synergistic-effect-with-cisplatin
#20
Cheng-Ming Hsu, Pai-Mei Lin, Yao-Te Tsai, Ming-Shao Tsai, Chun-Han Tseng, Sheng-Fung Lin, Ming-Yu Yang
NVP-BEZ235 is a dual phosphoinositide 3-kinase (PI3K)-mammalian target of rapamycin (mTOR) inhibitor. A dual approach targeting more than one downstream effector is a promising strategy for treating cancers. The aim of this study was to evaluate the effect of NVP-BEZ235 in treating FaDu hypopharyngeal squamous cell carcinoma (HSCC), either alone or in combination with cisplatin. We found mTOR expression was higher in patients with HSCC. In the in vitro study, treatment with NVP-BEZ235 alone attenuated cell proliferation and suppressed p-p70S6K and p-4E-BP1 expression in FaDu cells...
2018: Cell Death Discovery
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