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https://www.readbyqxmd.com/read/28238967/resveratrol-fuels-her2-and-er%C3%AE-positive-breast-cancer-behaving-as-proteasome-inhibitor
#1
Andreani Cristina, Bartolacci Caterina, Wijnant Kathleen, Crinelli Rita, Bianchi Marzia, Magnani Mauro, Hysi Albana, Iezzi Manuela, Amici Augusto, Marchini Cristina
The phytoestrogen resveratrol has been reported to possess cancer chemo-preventive activity on the basis of its effects on tumor cell lines and xenograft or carcinogen-inducible in vivo models. Here we investigated the effects of resveratrol on spontaneous mammary carcinogenesis using Δ16HER2 mice as HER2+/ERα+ breast cancer model. Instead of inhibiting tumor growth, resveratrol treatment (0.0001% in drinking water; daily intake of 4μg/mouse) shortened tumor latency and enhanced tumor multiplicity in Δ16HER2 mice...
February 26, 2017: Aging
https://www.readbyqxmd.com/read/28237819/the-complex-roles-of-mechanistic-target-of-rapamycin-in-adipocytes-and-beyond
#2
REVIEW
Peter L Lee, Su Myung Jung, David A Guertin
Having healthy adipose tissue is essential for metabolic fitness. This is clear from the obesity epidemic, which is unveiling a myriad of comorbidities associated with excess adipose tissue including type 2 diabetes, cardiovascular disease, and cancer. Lipodystrophy also causes insulin resistance, emphasizing the importance of having a balanced amount of fat. In cells, the mechanistic target of rapamycin (mTOR) complexes 1 and 2 (mTORC1 and mTORC2, respectively) link nutrient and hormonal signaling with metabolism, and recent studies are shedding new light on their in vivo roles in adipocytes...
February 22, 2017: Trends in Endocrinology and Metabolism: TEM
https://www.readbyqxmd.com/read/28228756/agonistic-anti-pdgf-receptor-autoantibodies-from-patients-with-systemic-sclerosis-impact-human-pulmonary-artery-smooth-muscle-cells-function-in-vitro
#3
Silvia Svegliati, Donatella Amico, Tatiana Spadoni, Colomba Fischetti, Doreen Finke, Gianluca Moroncini, Chiara Paolini, Cecilia Tonnini, Antonella Grieco, Marina Rovinelli, Armando Gabrielli
One of the earliest events in the pathogenesis of systemic sclerosis (SSc) is microvasculature damage with intimal hyperplasia and accumulation of cells expressing PDGF receptor. Stimulatory autoantibodies targeting PDGF receptor have been detected in SSc patients and demonstrated to induce fibrosis in vivo and convert in vitro normal fibroblasts into SSc-like cells. Since there is no evidence of the role of anti-PDGF receptor autoantibodies in the pathogenesis of SSc vascular lesions, we investigated the biologic effect of agonistic anti-PDGF receptor autoantibodies from SSc patients on human pulmonary artery smooth muscle cells and the signaling pathways involved...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28225024/rheb1-deletion-in-myeloid-cells-aggravates-ova-induced-allergic-inflammation-in-mice
#4
Kai Li, Yue Zhang, Kang Yan Liang, Song Xu, Xue Juan Zhou, Kang Tan, Jun Lin, Xiao Chun Bai, Cui Lan Yang
The small GTPase ras homolog enriched in brain (Rheb) is a downstream target of tuberous sclerosis complex 1/2 (TSC1/2) and an upstream activator of the mechanistic target of rapamycin complex 1 (mTORC1), the emerging essential modulator of M1/M2 balance in macrophages. However, the role and regulatory mechanisms of Rheb in macrophage polarization and allergic asthma are not known. In the present study, we utilized a mouse model with myeloid cell-specific deletion of the Rheb1 gene and an ovalbumin (OVA)-induced allergic asthma model to investigate the role of Rheb1 in allergic asthma and macrophage polarization...
February 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28224619/fl-asparaginase-mediated-downregulation-of-c-myc-promotes-1-25-oh-2-d3-induced-myeloid-differentiation-in-acute-myeloid-leukemia-cells
#5
Ju Han Song, Eunchong Park, Myun Soo Kim, Kyung-Min Cho, Su-Ho Park, Arim Lee, Jiseon Song, Hyeoung-Joon Kim, Jeong-Tae Koh, Tae Sung Kim
Treatment of acute myeloid leukemia (AML) largely depends on chemotherapy, but current regimens have been unsatisfactory for long-term remission. Although differentiation induction therapy utilizing 1,25(OH)2 D3 (VD3) has shown great promise for the improvement of AML treatment efficacy, severe side effects caused by its supraphysiological dose limit its clinical application. Here we investigated the combinatorial effect of l-asparaginase (ASNase)-mediated amino acid depletion and the latent alternation of VD3 activity on the induction of myeloid differentiation...
February 22, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28223419/papers-of-note-in-nature542-7641
#6
Annalisa M VanHook
This week's articles highlight a tRNA synthetase in mTORC1 signaling in fat cell metabolism and aging, the vulnerability of cancer cells to drugs that target proteostasis, and a mechanism by which stressed neurons expel protein aggregates and dysfunctional organelles.
February 21, 2017: Science Signaling
https://www.readbyqxmd.com/read/28223357/lipid-sensing-by-mtor-via-de-novo-synthesis-of-phosphatidic-acid
#7
Deepak Menon, Darin Salloum, Elyssa Bernfeld, Elizabeth Gorodetsky, Alla Akselrod, Maria A Frias, Jessica Sudderth, Pei-Hsuan Chen, Ralph DeBerardinis, David A Foster
mTOR, the mammalian target of rapamycin, integrates growth factor and nutrient signals to promote a transformation from catabolic to anabolic metabolism, cell growth, and cell cycle progression. Phosphatidic acid (PA)(2) interacts with the FRB (FK506 binding protein-12-rapamycin binding) domain of mTOR, which stabilizes both mTOR complexes - mTORC1 and mTORC2. We report here that mTORC1 and mTORC2 are activated in response to exogenously supplied fatty acids via the de novo synthesis of PA, a central metabolite for membrane phospholipid biosynthesis...
February 21, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28220207/considerations-on-mtor-regulation-at-serine-2448-implications-for-muscle-metabolism-studies
#8
REVIEW
Vandré Casagrande Figueiredo, James F Markworth, David Cameron-Smith
The mammalian target of rapamycin (mTOR) complex exerts a pivotal role in protein anabolism and cell growth. Despite its importance, few studies adequately address the complexity of phosphorylation of the mTOR protein itself to enable conclusions to be drawn on the extent of kinase activation following this event. In particular, a large number of studies in the skeletal muscle biology field have measured Serine 2448 (Ser2448) phosphorylation as a proxy of mTOR kinase activity. However, the evidence to be described is that Ser2448 is not a measure of mTOR kinase activity nor is a target of AKT activity and instead has inhibitory effects on the kinase that is targeted by the downstream effector p70S6K in a negative feedback loop mechanism, which is evident when revisiting muscle research studies...
February 20, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28218391/mapk3-1-participates-in-the-activation-of-primordial-follicles-through-mtorc1-kitl-signaling
#9
Yu Zhao, Yu Zhang, Jia Li, Nana Zheng, Xiaoting Xu, Jing Yang, Guoliang Xia, Meijia Zhang
The majority of ovarian primordial follicles are preserved in a dormant state to maintain the female reproductive lifespan, and only a few primordial follicles are activated to enter the growing follicle pool in each wave. Recent studies have shown that primordial follicular activation depends on mammalian target of rapamycin complex 1 (mTORC1)-KIT ligand (KITL) signaling in pre-granulosa cells and its receptor (KIT)-phosphoinositol 3 kinase (PI3K) signaling in oocytes. However, the upstream regulator of mTORC1 signaling is unclear...
February 20, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28218386/glucose-adsorption-to-chitosan-membranes-increases-proliferation-of-human-chondrocyte-via-mammalian-target-of-rapamycin-complex-1-and-sterol-regulatory-element-binding-protein-1-signaling
#10
Shun-Fu Chang, Kuo-Chin Huang, Chin-Chang Cheng, Yu-Ping Su, Ko-Chao Lee, Cheng-Nan Chen, Hsin-I Chang
BACKGROUND: Osteoarthritis (OA) is currently still an irreversible degenerative disease of the articular cartilage. Recent, dextrose (D-glucose) intraarticular injection prolotherapy for OA patients has been reported to benefit the chondrogenic stimulation of damaged cartilage. However, the detailed mechanism of glucose's effect on cartilage repair remains unclear. Chitosan, a naturally derived polysaccharide, has recently been investigated as a surgical or dental dressing to control breeding...
February 20, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28216612/macrophages-mtorc1-drives-granulomas
#11
Lucy Bird
No abstract text is available yet for this article.
March 2017: Nature Reviews. Immunology
https://www.readbyqxmd.com/read/28216025/pi3k-akt-mtor-inhibitors-in-breast-cancers-from-tumor-cell-signaling-to-clinical-trials
#12
REVIEW
Dey Nandini, De Pradip, Leyland-Jones Brian
Breast cancer (BC) is the most common women cancer and second most common cause of cancer death in women. A woman living in the United States has 12.3% lifetime risk of being diagnosed with BC. From the genomics point of view, the most common three subtypes of BC encountered in clinics are HR+, HER2+, and TNBC or basal-like BC. Estrogen receptor (ER) status or HER2 amplification or chemotherapy is not sufficient to understand the underlying mechanisms of disease progression and resistance (de novo or acquire)...
February 16, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28214587/paqr3-augments-amino-acid-deprivation-induced-autophagy-by-inhibiting-mtorc1-signaling
#13
Lin Wang, Yi Pan, Meiqin Huang, Xue You, Feifan Guo, Yan Chen
Amino acids are the key activators of the mTOR complex 1 (mTORC1, mainly composed of mTOR, Raptor and mLST8) required for cell growth and proliferation. On the other hand, deprivation of amino acids induces autophagy via inhibition of mTORC1 signaling. We report here that amino acid-induced mTORC1 activity and amino acid deprivation-induced autophagy are regulated by PAQR3, a tumor suppressor. At the cellular level, PAQR3 negatively regulates amino acid-induced activation of mTORC1. The N-terminal end of PAQR3 interacts with the WD domains of Raptor and mLST8 directly...
February 15, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28212548/branched-chain-amino-acids-prevent-hepatic-fibrosis-and-development-of-hepatocellular-carcinoma-in-a-non-alcoholic-steatohepatitis-mouse-model
#14
Kai Takegoshi, Masao Honda, Hikari Okada, Riuta Takabatake, Naoto Matsuzawa-Nagata, Jean S Campbell, Masashi Nishikawa, Tetsuro Shimakami, Takayoshi Shirasaki, Yoshio Sakai, Taro Yamashita, Toshinari Takamura, Takuji Tanaka, Shuichi Kaneko
Oral supplementation with branched-chain amino acids (BCAA; leucine, isoleucine, and valine) in patients with liver cirrhosis potentially suppresses the incidence of hepatocellular carcinoma (HCC) and improves event-free survival. However, the detailed mechanisms of BCAA action have not been fully elucidated. BCAA were administered to atherogenic and high-fat (Ath+HF) diet-induced nonalcoholic steatohepatitis (NASH) model mice. Liver histology, tumor incidence, and gene expression profiles were evaluated. Ath+HF diet mice developed hepatic tumors at a high frequency at 68 weeks...
February 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28211162/efficacy-of-the-oral-mtorc1-inhibitor-everolimus-in-relapsed-or-refractory-indolent-lymphoma
#15
N Nora Bennani, Betsy R LaPlant, Stephen M Ansell, Thomas M Habermann, David J Inwards, Ivana N Micallef, Patrick B Johnston, Luis F Porrata, Joseph P Colgan, Svetomir N Markovic, Grzegorz S Nowakowski, William R Macon, Craig B Reeder, Joseph R Mikhael, Donald W Northfelt, Irene M Ghobrial, Thomas E Witzig
Relapsed indolent lymphoma often becomes refractory to standard chemoimmunotherapy and requires new therapeutic strategies. Targeting the PI3K/mTOR pathway in several types of lymphoma has shown preclinical and clinical efficacy providing the rationale to test this strategy in the treatment of relapsed/refractory indolent lymphomas. We investigated in a phase II open label clinical trial the efficacy and safety of single agent everolimus, an inhibitor of mTORC1, in patients with relapsed/refractory indolent lymphomas...
February 17, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28204811/isopsoralen-mediated-suppression-of-bone-marrow-adiposity-and-attenuation-of-the-adipogenic-commitment-of-bone-marrow-derived-mesenchymal-stem-cells
#16
Jian Wang, Sheng-Fa Li, Ting Wang, Chun-Han Sun, Liang Wang, Min-Jun Huang, Jian Chen, Shao-Wei Zheng, Nan Wang, Ying-Jun Zhang, Tian-Yu Chen
Osteoporosis (OP) increases the risk of bone fractures and other complications, and is thus a major clinical problem. In this study, we examined the effect of isopsoralen on the differentiation of bone-derived marrow mesenchymal stem cells (BMSCs) into osteoblasts and adipocytes, as well as bone formation under osteoporotic conditions. Primary femoral BMSCs isolated from C57BL/6 mice were used to evaluate the isopsoralen-mediated regulation of the expression of alkaline phosphatase (ALP), osteocalcin (OCN) and runt-related transcription factor 2 (RUNX2) during osteogenesis 2 weeks...
March 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28202715/updating-of-aversive-memories-after-temporal-error-detection-is-differentially-modulated-by-mtor-across-development
#17
Lucille Tallot, Lorenzo Diaz-Mataix, Rosemarie E Perry, Kira Wood, Joseph E LeDoux, Anne-Marie Mouly, Regina M Sullivan, Valérie Doyère
The updating of a memory is triggered whenever it is reactivated and a mismatch from what is expected (i.e., prediction error) is detected, a process that can be unraveled through the memory's sensitivity to protein synthesis inhibitors (i.e., reconsolidation). As noted in previous studies, in Pavlovian threat/aversive conditioning in adult rats, prediction error detection and its associated protein synthesis-dependent reconsolidation can be triggered by reactivating the memory with the conditioned stimulus (CS), but without the unconditioned stimulus (US), or by presenting a CS-US pairing with a different CS-US interval than during the initial learning...
March 2017: Learning & Memory
https://www.readbyqxmd.com/read/28202675/the-molecular-basis-of-mtorc1-regulated-translation
#18
REVIEW
Carson C Thoreen
The mammalian target of rapamycin (mTOR) signaling pathway is a master regulator of cell growth throughout eukaryotes. The pathway senses nutrient and other growth signals, and then orchestrates the complex systems of anabolic and catabolic metabolism that underpin the growth process. A central target of mTOR signaling is the translation machinery. mTOR uses a multitude of translation factors to drive the bulk production of protein that growth requires, but also to direct a post-transcriptional program of growth-specific gene expression...
February 8, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28199315/szt2-dictates-gator-control-of-mtorc1-signalling
#19
Min Peng, Na Yin, Ming O Li
Mechanistic target of rapamycin complex 1 (TORC1) integrates nutrient signals to control cell growth and organismal homeostasis across eukaryotes. The evolutionarily conserved GATOR complex regulates mTORC1 signalling through Rag GTPases, and GATOR1 displays GTPase activating protein (GAP) activity for RAGA and RAGB (RAGA/B) and GATOR2 has been proposed to be an inhibitor of GATOR1. Furthermore, the metazoan-specific SESN proteins function as guanine nucleotide dissociation inhibitors (GDIs) for RAGA/B, and interact with GATOR2 with unknown effects...
February 15, 2017: Nature
https://www.readbyqxmd.com/read/28199306/kicstor-recruits-gator1-to-the-lysosome-and-is-necessary-for-nutrients-to-regulate-mtorc1
#20
Rachel L Wolfson, Lynne Chantranupong, Gregory A Wyant, Xin Gu, Jose M Orozco, Kuang Shen, Kendall J Condon, Sabrina Petri, Jibril Kedir, Sonia M Scaria, Monther Abu-Remaileh, Wayne N Frankel, David M Sabatini
The mechanistic target of rapamycin complex 1 (mTORC1) is a central regulator of cell growth that responds to diverse environmental signals and is deregulated in many human diseases, including cancer and epilepsy. Amino acids are a key input to this system, and act through the Rag GTPases to promote the translocation of mTORC1 to the lysosomal surface, its site of activation. Multiple protein complexes regulate the Rag GTPases in response to amino acids, including GATOR1, a GTPase activating protein for RAGA, and GATOR2, a positive regulator of unknown molecular function...
February 15, 2017: Nature
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