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target of rapamycin

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https://www.readbyqxmd.com/read/28447760/expression-of-mtor-70s6k-signaling-pathway-in-pathological-scar-fibroblasts-and-the-effects-of-resveratrol-intervention
#1
Zhi-Ming Tang, Xiao-Xiang Zhai, Ji-Cun Ding
The aim of the study was to examine the expression of mammalian target of rapamycin (mTOR)/70S6K signaling pathway in pathological scar fibroblasts and the effects of resveratrol (Res) intervention. The mTOR and 70S6K in pathological scar and normal skin fibroblasts were detected by immunofluorescence following treatment with different concentrations of Res. RT-PCR and western blot analysis were used to detect the expression of mTOR and 70S6K mRNA and protein, respectively. Immunofluorescence showed that the expression of 70S6K and mTOR was significantly enhanced in pathological scar fibroblasts, and mainly expressed in the nucleus, but not in normal skin fibroblasts...
March 16, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28447735/mice-endometrium-receptivity-in-early-pregnancy-is-impaired-by-maternal-hyperinsulinemia
#2
Runqin Li, Juan Wu, Junlin He, Yingxiong Wang, Xueqing Liu, Xuemei Chen, Chao Tong, Yubin Ding, Yan Su, Wenqi Chen, Chen Zhang, Rufei Gao
Previous studies have investigated the lower embryo implantation rates in women with polycystic ovary syndrome, obesity and type 2 diabetes, and specifically the association between the abnormal oocyte and embryo and hyperinsulinemia. The importance of hyperinsulinemia on maternal endometrium receptivity remains to be elucidated. The present study used a hyperinsulinemic mouse model to determine whether hyperinsulinemia may affect endometrial receptivity. An insulin intervention mouse model was first established...
March 14, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28446743/mammalian-target-of-rapamycin-mtor-regulates-transforming-growth-factor-%C3%AE-1-tgf-%C3%AE-1-induced-epithelial-mesenchymal-transition-via-decreased-pyruvate-kinase-m2-pkm2-expression-in-cervical-cancer-cells
#3
Ke-Yan Cheng, Min Hao
BACKGROUND Epithelial-mesenchymal transition (EMT) plays an important role in cancer tumorigenesis. Transforming growth factor β1 (TGF-β1) can induced EMT, which could increase tumor migration and invasion. Moreover, recent studies have been proven that mammalian target of rapamycin (mTOR) is a critical regulator of EMT. We investigated the mechanisms of mTOR in transforming growth factor β1 (TGF-β1)-induced EMT in cervical cancer cells. MATERIAL AND METHODS HeLa and SiHa cells were treated with 10 ng/ml TGF-β1 to induce EMT...
April 27, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28446728/inhibition-of-hsf1-suppresses-the-growth-of-hepatocarcinoma-cell-lines-in-vitro-and-akt-driven-hepatocarcinogenesis-in-mice
#4
Antonio Cigliano, Chunmei Wang, Maria G Pilo, Marta Szydlowska, Stefania Brozzetti, Gavinella Latte, Giovanni M Pes, Rosa M Pascale, Maria A Seddaiu, Gianpaolo Vidili, Silvia Ribback, Frank Dombrowski, Matthias Evert, Xin Chen, Diego F Calvisi
Upregulation of the heat shock transcription factor 1 (HSF1) has been described as a frequent event in many cancer types, but its oncogenic role in hepatocellular carcinoma (HCC) remains poorly delineated. In the present study, we assessed the function(s) of HSF1 in hepatocarcinogenesis via in vitro and in vivo approaches. In particular, we determined the importance of HSF1 on v-Akt murine thymoma viral oncogene homolog (AKT)-induced liver cancer development in mice. We found that knockdown of HSF1 activity via specific siRNA triggered growth restraint by suppressing cell proliferation and inducing massive cell apoptosis in human HCC cell lines...
April 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28446154/effects-of-escitalopram-and-paroxetine-on-mtorc1-signaling-in-the-rat-hippocampus-under-chronic-restraint-stress
#5
Mi Kyoung Seo, Cheol Min Choi, Roger S McIntyre, Hye Yeon Cho, Chan Hong Lee, Rodrigo B Mansur, Yena Lee, Jae-Hon Lee, Young Hoon Kim, Sung Woo Park, Jung Goo Lee
BACKGROUND: Recent studies have suggested that the activation of mammalian target of rapamycin (mTOR) signaling may be related to antidepressant action. Therefore, the present study evaluated whether antidepressant drugs would exert differential effects on mTOR signaling in the rat hippocampus under conditions of chronic restraint stress. Male Sprague-Dawley rats were subjected to restraint stress for 6 h/days for 21 days with either escitalopram (10 mg/kg) or paroxetine (10 mg/kg) administered after the chronic stress procedure...
April 26, 2017: BMC Neuroscience
https://www.readbyqxmd.com/read/28445971/stat3-regulates-glycolysis-via-targeting-hexokinase-2-in-hepatocellular-carcinoma-cells
#6
Man Li, Rui Jin, Weihua Wang, Tieying Zhang, Jiao Sang, Na Li, Qunying Han, Wenxuan Zhao, Chunyan Li, Zhengwen Liu
Signal transducer and activator of transcription 3 (STAT3) and hexokinase 2 (HK2) are involved in hepatocellular carcinoma (HCC). Deregulation of cellular energetics involving an increase in glycolysis is a characteristic of HCC. This study examined whether STAT3 regulates HCC glycolysis through the HK2 pathway in HCC cells. Human HCC cell lines HepG2 and Hep3B cells were transfected with pcDNA3.1(+)-EGFP-STAT3, STAT3 siRNA and HK2 siRNA, respectively, or treated with rapamycin, an inhibitor of mammalian target of rapamycin (mTOR), and the effects on STAT3 and HK2 expression and cell glycolysis were determined...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445935/inhibition-of-mtorc2-component-rictor-impairs-tumor-growth-in-pancreatic-cancer-models
#7
Katharina M Schmidt, Claus Hellerbrand, Petra Ruemmele, Christoph W Michalski, Bo Kong, Alexander Kroemer, Christina Hackl, Hans J Schlitt, Edward K Geissler, Sven A Lang
Mammalian Target of Rapamycin complex 2 (mTORC2) and its regulatory component Rapamycin-insensitive companion of mTOR (RICTOR) are increasingly recognized as important players in human cancer development and progression. However, the role of RICTOR in human pancreatic ductal adenocarcinoma (PDAC) is unclear so far. Here, we sought to analyze the effects of RICTOR inhibition in human pancreatic cancer cell lines in vitro and in vivo. Furthermore, RICTOR expression was determined in human PDAC samples. Results demonstrate that depletion of RICTOR with siRNA (transient knock-down) or shRNA (stable knock-down) has an inhibitory effect on tumor growth in vitro...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445821/the-ampk-mtor-pathway-is-involved-in-d-dopachrome-tautomerase-gene-transcription-in-adipocytes-differentiated-from-sgbs-cells-a-human-preadipocyte-cell-line
#8
Takeo Iwata, Kyoko Kuribayashi, Masahiko Nakasono, Noriko Saito-Tarashima, Noriaki Minakawa, Noriko Mizusawa, Rie Kido, Katsuhiko Yoshimoto
In adipose tissue, D-dopachrome tautomerase (DDT), a cytokine with structural similarity to macrophage migration inhibitory factor, is mainly expressed in adipocytes rather than preadipocytes and acts as an anti-obesity adipokine in an autocrine manner. However, its transcriptional regulation is largely unknown. In order to explore molecules affecting DDT transcription, a chemical library screening using HEK293 cells stably expressing a DDT promoter-reporter construct was performed. Several derivatives of 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR), an AMP-activated protein kinase (AMPK) activator, were identified as transcriptional activators of the DDT gene...
April 23, 2017: Cytokine
https://www.readbyqxmd.com/read/28445619/mtor-inhibitors-and-risk-for-chronic-antibody-mediated-rejection-after-kidney-transplantation-where-are-we-now
#9
REVIEW
Philippe Grimbert, Olivier Thaunat
Antibody-mediated rejection (AMR) usually starts with generation of donor-specific anti-HLA antibodies (DSA), arising from a B-cell response to antigen recognition. In vitro and preclinical data demonstrate that mammalian target of rapamycin (mTOR) inhibition attenuates the mTOR-mediated intracellular signaling pathway involved in AMR-related kidney damage. The limited available data from immunological studies in kidney transplant patients, however, have not shown such effects in vivo. In terms of clinical immunosuppression, the overriding influence on rates of de novo DSA (dnDSA) or AMR - regardless of the type of regimen - is patient adherence...
April 26, 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/28442920/a-blockade-of-pd-l1-produced-antitumor-and-antimetastatic-effects-in-an-orthotopic-mouse-pancreatic-cancer-model-via-the-pi3k-akt-mtor-signaling-pathway
#10
Lei Zhao, Cheng Li, Fei Liu, Yonghong Zhao, Jun Liu, Ye Hua, Jinyang Liu, Jiapeng Huang, Chunlin Ge
BACKGROUND: Pancreatic cancer is one of the most aggressive and intractable malignant tumors, and most deaths from pancreatic cancer are related to metastases. It has been demonstrated in vitro that overexpression of programmed death-ligand 1 (PD-L1) correlates with a lack of phosphatase and tensin homologue (PTEN) expression in pancreatic cancer tissue. This loss of PTEN expression may aberrantly activate the phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway, and thereby promote tumor cell survival, proliferation, and disease progression...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28442891/spotlight-on-nivolumab-in-the-treatment-of-renal-cell-carcinoma-design-development-and-place-in-therapy
#11
REVIEW
Vyshak Alva Venur, Monika Joshi, Kenneth G Nepple, Yousef Zakharia
Several tyrosine kinase inhibitors targeting the vascular endothelial growth factor receptors and molecules inhibiting the mammalian target of rapamycin are being used for management of metastatic renal cell carcinoma (mRCC); however, there is still a potential for improvement. Immune checkpoint inhibitors like nivolumab and other PD-1/PD-L1 inhibitors provide an alternative approach for patients with mRCC. In this article, the authors review the safety profile and outcomes of phase 1, 2, and 3 clinical trials of nivolumab in mRCC...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28442548/keratin-8-18-regulation-of-insulin-receptor-signaling-and-trafficking-in-hepatocytes-through-a-concerted-phosphoinositide-dependent-akt-and-rab5-modulation
#12
Alexandra Roux, Anne Loranger, Josée N Lavoie, Normand Marceau
Keratins (Ks) are epithelial cell intermediate filament (IF) proteins that are expressed as pairs in a differentiation-regulated manner. Hepatocyte IFs are made only of K8/K18 pairs, which means that a K8 loss in K8-null mice leads to degradation of K18. Functionally, there is accumulating evidence that IFs contribute to signaling platforms. Here, we investigate the role of K8/K18 IFs in the regulation of insulin receptor (IR) signaling and trafficking in hepatocytes. We find that the IR substrate 1 (IRS1)/PI3K/Akt signaling cascade-downstream of IR-display prolonged activation in K8-null compared with wild-type hepatocytes...
April 25, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28442526/morphoproteomic-guided-treatment-of-chemotherapy-resistant-colon-cancer-using-natural-based-therapies-a-case-study
#13
John Thomas Rogers, Robert E Brown, Jamie Jay Buryanek, Priya Weerasinghe
Colorectal cancer was estimated to have the fourth newest incident rate and to have the second highest death rate in 2015 according to the American Cancer Society. There were an estimated 132,700 new diagnoses of colorectal cancer made and approximately 69,000 deaths in 2015 attributing to this form of cancer. 5-fluorouracil (5-FU) or 5-FU with oxaliplatin (FOLFOX) continues to be the standard treatment protocol for patients presenting with colorectal cancer. However, treatment with FOLFOX and conventional chemotherapy has shown to lead to cancer recurrence and a number of toxic side effects...
March 2017: Annals of Clinical and Laboratory Science
https://www.readbyqxmd.com/read/28442256/functional-evaluation-of-synthetic-flavonoids-and-chalcones-for-potential-antiviral-and-anticancer-properties
#14
Nelly Mateeva, Suresh V K Eyunni, Kinfe K Redda, Ucheze Ononuju, Tony D Hansberry, Cecilia Aikens, Anita Nag
Flavonoids, stilbenes, and chalcones are plant secondary metabolites that often possess diverse biological activities including anti-inflammatory, anti-cancer, and anti-viral activities. The wide range of bioactivities poses a challenge to identify their targets. Here, we studied a set of synthetically generated flavonoids and chalcones to evaluate for their biological activity, and compared similarly substituted flavonoids and chalcones. Substituted chalcones, but not flavonoids, showed inhibition of viral translation without significantly affecting viral replication in cells infected with hepatitis C virus (HCV)...
April 13, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28440424/therapeutic-potential-of-the-antidiabetic-drug-metformin-in-small-bowel-adenocarcinoma
#15
Taiga Chiyo, Kiyohito Kato, Hisakazu Iwama, Shintaro Fujihara, Koji Fujita, Tomoko Tadokoro, Kyoko Ohura, Eri Samukawa, Yoshimi Yamana, Nobuya Kobayashi, Tae Matsunaga, Noriko Nishiyama, Maki Ayaki, Tatsuo Yachida, Asahiro Morishita, Hideki Kobara, Hirohito Mori, Tsutomu Masaki
Small bowel adenocarcinoma (SBAC) accounts for 3% of all gastrointestinal tract tumors and approximately 0.5% of all cancer cases. Recent studies have indicated that the use of metformin, one of the most commonly prescribed antidiabetic drugs, is associated with a better prognosis for certain malignant diseases. However, there have been no reports on the effect of metformin in SBAC. In the present study, we evaluated the effect of metformin on human SBAC cell proliferation in vitro and in vivo and identified the microRNAs (miRNAs) associated with its antitumor effects...
April 20, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28439198/assessment-of-tumors-in-children-with-tuberous-sclerosis-a-single-centre-s-experience
#16
Suna Emir, Şadan Hacısalihoğlu, Derya Özyörük, Filiz Ekici, Aydan Değerliyurt, Alev Güven, İlker Çetin
AIM: As a result of mutations in TSC1 (9q34) and TSC2 (16p13.3) tumor supressor genes, the mammalian target of the rapamycin (mTor) signaling pathway is overactivated in patients with tuberous sclerosis. Abnormal cell proliferation and differentiation is responsible for the growth several different tumors. The aim of this study was to review tumors in our patients with tuberous sclerosis. MATERIAL AND METHODS: Thirty-six patients with tuberous sclerosis were reviewed retrospectively in terms of age, sex, family history, clinical findings, presence of tumors, and treatments...
March 2017: Türk Pediatri Arşivi
https://www.readbyqxmd.com/read/28437004/4-4-dichlorodiphenyltrichloroethane-ddt-and-4-4-dichlorodiphenyldichloroethylene-dde-inhibit-myogenesis-in-c2c12-myoblasts
#17
Jonggun Kim, Min Young Park, Yoo Kim, Kyong Sup Yoon, John Marshall Clark, Yeonhwa Park, Kwang-Youn Whang
BACKGROUND: Most countries have banned the use of 4,4'-Dichlorodiphenyltrichloroethane (DDT). However, due to its extremely high lipophilic characteristics, DDT and its metabolite 4,4'-dichlorodiphenyldichloroethylene (DDE) are ubiquitous in the environment and in many types of food. The positive correlation between exposure to insecticides, including DDT and DDE, and weight gain, resulting in impaired energy metabolism in offspring following perinatal DDT and DDE exposure was previously reported...
April 24, 2017: Journal of the Science of Food and Agriculture
https://www.readbyqxmd.com/read/28436950/mre11-stability-is-regulated-by-ck2-dependent-interaction-with-r2tp-complex
#18
P von Morgen, K Burdova, T G Flower, N J O'Reilly, S J Boulton, S J Smerdon, L Macurek, Z Hořejší
The MRN (MRE11-RAD50-NBS1) complex is essential for repair of DNA double-strand breaks and stalled replication forks. Mutations of the MRN complex subunit MRE11 cause the hereditary cancer-susceptibility disease ataxia-telangiectasia-like disorder (ATLD). Here we show that MRE11 directly interacts with PIH1D1, a subunit of heat-shock protein 90 cochaperone R2TP complex, which is required for the assembly of large protein complexes, such as RNA polymerase II, small nucleolar ribonucleoproteins and mammalian target of rapamycin complex 1...
April 24, 2017: Oncogene
https://www.readbyqxmd.com/read/28435223/efficacy-of-the-dual-pi3k-and-mtor-inhibitor-nvp-bez235-in-combination-with-imatinib-mesylate-against-chronic-myelogenous-leukemia-cell-lines
#19
Pengliang Xin, Chuntuan Li, Yan Zheng, Qunyi Peng, Huifang Xiao, Yuanling Huang, Xiongpeng Zhu
BACKGROUND: Phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway is a therapy target of cancer. We aimed to confirm the effect of dual PI3K/mTOR inhibitor NVP-BEZ235 on proliferation, apoptosis, and autophagy of chronic myelogenous leukemia (CML) cells and sensitivity of tyrosine kinase inhibitor in vitro. METHODS: Two human CML cell lines, K562 and KBM7R (T315I mutant strain), were used. The proliferation of CML cells was detected by MTS (Owen's reagent) assay...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28434735/effects-of-graded-removal-of-lysine-from-an-intravenously-infused-amino-acid-mixture-on-lactation-performance-and-mammary-amino-acid-metabolism-in-lactating-goats
#20
C L Guo, Y T Li, X Y Lin, M D Hanigan, Z G Yan, Z Y Hu, Q L Hou, F G Jiang, Z H Wang
To investigate responses of milk protein synthesis and mammary AA metabolism to a graded decrease of postruminal Lys supply, 4 lactating goats fitted with jugular vein, mammary vein, and carotid artery catheters and transonic blood flow detectors on the external pudic artery were used in a 4 × 4 Latin square experiment. Goats were fasted for 24 h and then received a 9-h intravenous infusion of an AA mixture plus glucose. Milk yield was recorded and samples were taken in h 2 to 8 of the infusion period; a mammary biopsy was performed in the last hour...
April 20, 2017: Journal of Dairy Science
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