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https://www.readbyqxmd.com/read/28445935/inhibition-of-mtorc2-component-rictor-impairs-tumor-growth-in-pancreatic-cancer-models
#1
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/28445712/consider-the-context-ras-erk-and-pi3k-akt-mtor-signaling-outcomes-are-pituitary-cell-type-specific
#2
REVIEW
Allyson K Roof, Arthur Gutierrez-Hartmann
Conserved signaling pathways are critical regulators of pituitary homeostasis and, when dysregulated, contribute to adenoma formation. Pituitary adenomas are typically benign and rarely progress to malignant cancer. Pituitary and other neuroendocrine cell types often display non-proliferative responses to ERK and PI3K, in contrast to non-endocrine cell types which typically proliferate in response to ERK and PI3K activation. These differences likely contribute to the infrequent progression to malignancy in many endocrine tumors...
April 23, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28445155/retinoblastoma-cells-activate-the-akt-pathway-and-are-vulnerable-to-the-pi3k-mtor-inhibitor-nvp-bez235
#3
Chencheng Xie, Matthew J Freeman, Huarui Lu, Xiaohong Wang, Colleen L Forster, Aaron L Sarver, Timothy C Hallstrom
Retinoblastoma is a pediatric cancer of the retina most often caused by inactivation of the retinoblastoma (RB1) tumor suppressor gene. We previously showed that Rb1 loss cooperates with either co-activating the phosphatidylinositol 3-kinase (PI3K)/AKT pathway, or co-deleting Pten, to initiate retinoblastoma tumors in mice. The objectives of this study were to determine if the AKT pathway is activated in human retinoblastomas and the extent that anti-PI3K therapy induces apoptosis in retinoblastoma cells, alone or in combination with the DNA damaging drugs carboplatin and topotecan...
April 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28443090/immunometabolic-regulations-mediated-by-coinhibitory-receptors-and-their-impact-on-t-cell-immune-responses
#4
REVIEW
Nikolaos Patsoukis, Jessica D Weaver, Laura Strauss, Christoph Herbel, Pankaj Seth, Vassiliki A Boussiotis
Host immunity provides wide spectrum protection that serves to eradicate pathogens and cancer cells, while maintaining self-tolerance and immunological homeostasis. Ligation of the T cell receptor (TCR) by antigen activates signaling pathways that coordinately induce aerobic glycolysis, mitochondrial activity, anabolic metabolism, and T effector cell differentiation. Activation of PI3K, Akt, and mTOR triggers the switch to anabolic metabolism by inducing transcription factors such as Myc and HIF1, and the glucose transporter Glut1, which is pivotal for the increase of glucose uptake after T cell activation...
2017: Frontiers in Immunology
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
#5
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/28442505/overexpressed-fatty-acid-synthase-in-gastrointestinal-stromal-tumors-targeting-a-progression-associated-metabolic-driver-enhances-the-antitumor-effect-of-imatinib
#6
Chien-Feng Li, Fu-Min Fang, Yeng-Yang Chen, Ting-Ting Liu, Ti-Chun Chan, Shih-Chen Yu, Li-Tzong Chen, Hsuan-Ying Huang
Purpose: In gastrointestinal stromal tumors (GISTs), lipid-metabolizing enzymes remain underexplored, including fatty acid synthase (FASN). <p>Experimental Design: Forty GISTs were quantitated for FASN mRNA abundance. FASN immunoexpression was informative in 350 GISTs, including 213 with known KIT/PDGFRA/BRAF genotypes. In imatinib-resistant FASN-overexpressing GIST cells, the roles of overexpressed FASN and FASN-targeting C75 in tumor phenotypes, apoptosis and autophagy, KIT transcription, PI3K/AKT/mTOR activation, and imatinib resistance were analyzed by RNA interference or myristoylated-AKT transfection...
April 25, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28442344/mir-221-regulates-cd44-in-hepatocellular-carcinoma-through-the-pi3k-akt-mtor-pathway
#7
Jihye Kim, Jinmai Jiang, Mohamed Badawi, Thomas D Schmittgen
CD44 and miR-221 are upregulated in hepatocellular carcinoma (HCC) cell lines and tumors, however a connection between the two has not been identified. As the expression of miR-221 directly correlated with CD44 in HCC cells, we hypothesized that miR-221 may directly or indirectly regulate CD44 expression. Inhibition of miR-221 with antisense in Sk-Hep-1 or SNU-449 cell lines reduced CD44 protein expression while miR-221 mimic increased CD44 protein levels. miR-221 antisense did not alter the CD44 mRNA levels in Sk-Hep-1 or SNU-449 cells suggesting that regulation of CD44 protein occurs post transcriptionally...
April 22, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28440448/modified-panax-ginseng-extract-regulates-autophagy-by-ampk-signaling-in-a549-human-lung-cancer-cells
#8
Hwa-Seung Yoo, Jung Min Kim, Eunbi Jo, Chong-Kwan Cho, Seung-Yeul Lee, Hwan Su Kang, Min-Goo Lee, Pei-Ying Yang, Ik-Soon Jang
Panax ginseng has been used worldwide as a traditional medicine for the treatment of cancer and other diseases. The antiproliferative activity of ginseng has been increased after enzymatic processing of ginseng saponin, which may result in the accumulation of minor saponins, such as Rh2, Rg3, compound K and protopanaxatriol type (PPT) in modified regular ginseng extract (MRGX). In the present study, the anticancer activity and the associated mechanisms of MRGX were investigated using A549 human lung cancer cells...
April 20, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28440057/overcoming-linsitinib-intrinsic-resistance-through-inhibition-of-nuclear-factor-%C3%AE%C2%BAb-signaling-in-esophageal-squamous-cell-carcinoma
#9
Junzhou Wu, Kaiyan Chen, Fanrong Zhang, Jiaoyue Jin, Nan Zhang, Dan Li, Lisha Ying, Wei Chen, Herbert Yu, Weimin Mao, Dan Su
The aim of this study is to evaluate the efficacy of insulin-like growth factor 1 receptor (IGF-1R) inhibitor Linsitinib, in esophageal squamous cell carcinoma (ESCC), and to characterize special biomarker to screen Linsitinib-sensitive patients as well as explore the molecular-resistant mechanism to Linsitinib in ESCC. Our study evaluated the sensitivity of insulin-like growth factor 1 receptor (IGF-1R) inhibitor, Linsitinib in ESCC cells with MTT assay. After Linsitinib treatment, the expressions of downstream signaling molecules and apoptosis pathways were measured by western blot...
April 24, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28437835/pten-downregulation-promotes-%C3%AE-oxidation-to-fuel-hypertrophic-liver-growth-after-hepatectomy-in-mice
#10
Ekaterina Kachaylo, Christoph Tschuor, Nicolas Calo, Nathalie Borgeaud, Perparim Limani, Anne-Christine Piguet, Jean-Francois Dufour, Michelangelo Foti, Rolf Graf, Pierre A Clavien, Bostjan Humar
In regenerating liver, hepatocytes accumulate lipids before the major wave of parenchymal growth. This transient, regeneration-associated steatosis (TRAS) is required for liver recovery, but its purpose is unclear. The tumor suppressor PTEN is a key inhibitor of the AKT-mTOR axis that regulates growth and metabolic adaptations after hepatectomy. In quiescent liver, PTEN causes pathological steatosis when lost, while its role in regenerating liver remains unknown. Here, we show that PTEN downregulation promotes liver growth in a TRAS-dependent way...
April 24, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
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
#11
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/28433890/il-37-induces-autophagy-in-hepatocellular-carcinoma-cells-by-inhibiting-the-pi3k-akt-mtor-pathway
#12
Ting-Ting Li, Di Zhu, Tong Mou, Zhen Guo, Jun-Liang Pu, Qing-Song Chen, Xu-Fu Wei, Zhong-Jun Wu
Autophagy is an intracellular "self-eating" process that is closely related to inflammation and cellular immunity. New studies indicate that autophagy is also involved in tumor suppression. The anti-inflammatory cytokine interleukin-37 (IL-37) has been shown to have tumor-suppressive abilities in hepatocellular carcinoma (HCC). Notably, autophagy appears to play a dual role in the development of HCC and may be involved in both tumorigenesis and tumor suppression. However, the potential role of IL-37 in autophagy is currently unknown...
April 20, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28433710/down-regulation-of-islet-amyloid-polypeptide-expression-induces-death-of-human-annulus-fibrosus-cells-via-mitochondrial-and-death-receptor-pathways
#13
Xinghuo Wu, Kun Wang, Wenbin Hua, Shuai Li, Xianzhe Liu, Wei Liu, Yu Song, Yukun Zhang, Zengwu Shao, Cao Yang
Islet amyloid polypeptide (IAPP) exerts its biological effects by participating in the regulation of glucose metabolism and cell apoptosis. The main goal of the present study was to investigate the expression of IAPP in degenerated intervertebral disc tissue and IAPP's modulation of extracellular matrix (ECM) catabolic and anabolic genes in human AF cells. We found that the expression of IAPP, the calcitonin receptor, and receptor activity modifying protein decreased considerably in AF cells during the progression of intervertebral disc degeneration (IDD)...
April 19, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28432555/rotundarpene-inhibits-tnf-%C3%AE-induced-activation-of-the-akt-mtor-and-nf-%C3%AE%C2%BAb-pathways-and-the-jnk-and-p38-associated-with-production-of-reactive-oxygen-species
#14
Arum Kim, Yoon Jeong Nam, Yong Kyoo Shin, Min Sung Lee, Dong Suep Sohn, Chung Soo Lee
Ilex Rotunda Thunb has been shown to have anti-inflammatory and antioxidant effects. In human keratinocytes, we investigated the effect of rotundarpene (4-caffeoyl-3-methyl-but-2-ene-1,4-diol) on the TNF-α-stimulated production of inflammatory mediators in relation to the Akt, mTOR, and NF-κB pathways, and the JNK and p38-MAPK. Rotundarpene, Akt inhibitor, Bay 11-7085, rapamycin, and N-acetylcysteine inhibited the TNF-α-stimulated production of cytokines and chemokines, increase in the levels of p-Akt and mTOR, activation of NF-κB, and production of reactive oxygen species in keratinocytes...
April 21, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28431975/liposomal-curcumin-alters-chemosensitivity-of-breast-cancer-cells-to-adriamycin-via-regulating-microrna-expression
#15
Siying Zhou, Jian Li, Hanzi Xu, Sijie Zhang, Xiu Chen, Wei Chen, Sujin Yang, Shanliang Zhong, Jianhua Zhao, Jinhai Tang
BACKGROUND: Emerging evidence suggests that curcumin can overcome drug resistance to classical chemotherapies, but poor bioavailability and low absorption have limited its clinical use and the mechanisms remain unclear. Also, Adriamycin (Adr) is one of the most active cytotoxic agents in breast cancer; however, the high resistant rate of Adr leads to a poor prognosis. METHODS: We utilized encapsulation in liposomes as a strategy to improve the bioavailability of curcumin and demonstrated that liposomal curcumin altered chemosensitivity of Adr-resistant MCF-7 human breast cancer (MCF-7/Adr) by MTT assay...
April 18, 2017: Gene
https://www.readbyqxmd.com/read/28430287/dysembryoplastic-neuroepithelial-tumour-insight-into-the-pathology-and-pathogenesis
#16
Iwona Sontowska, Ewa Matyja, Jacek Malejczyk, Wieslawa Grajkowska
<i>Dysembryoplastic neuroepithelial tumour (DNT) is categorized as a benign glioneuronal neoplasm affecting children and young adults with chronic epileptic seizures. It is characterized by predominant intracortical localization and nodular architecture. Dysembryoplastic neuroepithelial tumour usually demonstrates a distinctive morphological pattern with a specific glioneuronal element but occasionally, its morphological picture is heterogeneous and unspecific. Thus, considering the morphology of DNT, three different histopathological subtypes are distinguished: simple, complex, and non-specific and diffuse...
2017: Folia Neuropathologica
https://www.readbyqxmd.com/read/28428627/glucocorticoids-suppress-antimicrobial-autophagy-and-nitric-oxide-production-and-facilitate-mycobacterial-survival-in-macrophages
#17
Jinli Wang, Ruining Wang, Hui Wang, Xiaofan Yang, Jiahui Yang, Wenjing Xiong, Qian Wen, Li Ma
Chronic administration of glucocorticoids has been shown to render individuals highly susceptible to mycobacterial infection and lead to reactivation of latent bacilli. However, the effect of glucocorticoids on innate anti-mycobacterial defense, especially in macrophages remains largely unknown. Here, we found that glucocorticoids inhibited the innate immune response, antimicrobial nitric oxide production and autophagy in mycobacteria-challenged macrophages. Meanwhile, maturation and acidification of mycobacterial phagosomes were attenuated in RAW264...
April 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28427860/differential-mtor-pathway-profiles-in-bladder-cancer-cell-line-subtypes-to-predict-sensitivity-to-mtor-inhibition
#18
Andrew M Hau, Manando Nakasaki, Kazufumi Nakashima, Goutam Krish, Donna E Hansel
BACKGROUND: Molecular classification of bladder cancer has been increasingly proposed as a potential tool to predict clinical outcomes and responses to chemotherapy. Here we focused on mechanistic target of rapamycin (mTOR) inhibition as a chemotherapeutic strategy and characterized the expression profile of mTOR signaling targets in representative bladder cancer cell lines from basal, luminal, and either basal/luminal ("non-type") molecular subtypes. MATERIALS AND METHODS: Protein and mRNA expression of mTOR signaling components from representative luminal (RT4 and RT112), basal (SCaBER and 5637), and nontype (T24 and J82) bladder cancer cell line subtypes were determined by Western blot and database mining analysis of the Cancer Cell Line Encyclopedia...
April 18, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/28427592/pathologic-active-mtor-mutation-in-brain-malformation-with-intractable-epilepsy-leads-to-cell-autonomous-migration-delay
#19
Sae Hanai, Sayuri Sukigara, Hongmei Dai, Tomoo Owa, Shin-Ichi Horike, Taisuke Otsuki, Takashi Saito, Eiji Nakagawa, Naoki Ikegaya, Takanobu Kaido, Noriko Sato, Akio Takahashi, Kenji Sugai, Yuko Saito, Masayuki Sasaki, Mikio Hoshino, Yu-Ichi Goto, Schuichi Koizumi, Masayuki Itoh
The activation of phosphatidylinositol 3-kinase-AKTs-mammalian target of rapamycin cell signaling pathway leads to cell overgrowth and abnormal migration and results in various types of cortical malformations, such as hemimegalencephaly (HME), focal cortical dysplasia, and tuberous sclerosis complex. However, the pathomechanism underlying abnormal cell migration remains unknown. With the use of fetal mouse brain, we performed causative gene analysis of the resected brain tissues from a patient with HME and investigated the pathogenesis...
May 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28427207/mir-205-inhibits-cell-growth-by-targeting-akt-mtor-signaling-in-progesterone-resistant-endometrial-cancer-ishikawa-cells
#20
Zhihong Zhuo, Huimin Yu
PURPOSE: miR-205 is significantly up-regulated in endometrioid adenocarcinoma. In this study, the significant anticancer effect of a miR-205 inhibitor was investigated in both endometrial carcinoma and progesterone-resistant endometrial carcinoma cells. RESULTS: Compared with Ishikawa endometrial cancer cells, miR-205 was expressed at higher levels in a progesterone-resistant (PR) sub-cell line. Inhibition of miR-205 suppressed the growth of cancer cells in a dose- and time-dependent manner...
March 3, 2017: Oncotarget
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