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https://www.readbyqxmd.com/read/28212559/the-selective-mek1-inhibitor-selumetinib-enhances-the-antitumor-activity-of-everolimus-against-renal-cell-carcinoma-in-vitro-and-in-vivo
#1
Yun Zou, Jianfeng Wang, Xuejiao Leng, Jiwei Huang, Wei Xue, Jin Zhang, Yiran Huang
Renal cell carcinoma (RCC) is a urologic malignant cancer and often diagnosed at an advanced stage, which results in high mortality. Targeted therapy may improve the quality of life and survival of patients who are not suitable for nephrectomy. Everolimus, an mTOR inhibitor, is currently used as sequential or second-line therapy for RCC refractory to Sunitinib or sorafenib. However, its efficiency is palliative. In this study, we evaluated whether the antitumor activity of everolimus against RCC is enhanced by Selumetinib, a selective MEK1 inhibitor...
February 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28212545/snora74b-gene-silencing-inhibits-gallbladder-cancer-cells-by-inducing-phlpp-and-suppressing-akt-mtor-signaling
#2
Yiyu Qin, Li Meng, Yang Fu, Zhiwei Quan, Mingzhe Ma, Mingzhe Weng, Zhengdong Zhang, Cuixiang Gao, Xinghua Shi, Koulan Han
Small nucleolar RNAs (snoRNAs) have been implicated in the development of many cancers. We therefore examined the differential expression of snoRNAs between gallbladder cancer (GBC) tissues and matched adjacent non-tumor tissues using expression microarray analysis with confirmation by quantitative real-time PCR (qRT-PCR). Western blot analysis showed that SNORA74B levels were higher in GBC than non-tumor tissues. SNORA74B expression was positively associated with local invasion, advanced TNM stage, CA19-9 level, and Ki67 expression in patients with GBC, while it was negatively associated with expression of PHLPP, an endogenous Akt inhibitor...
February 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28212537/itraconazole-exerts-its-anti-melanoma-effect-by-suppressing-hedgehog-wnt-and-pi3k-mtor-signaling-pathways
#3
Guanzhao Liang, Musang Liu, Qiong Wang, Yongnian Shen, Huan Mei, Dongmei Li, Weida Liu
Malignant melanoma is the deadliest form of all skin cancers. Itraconazole, a commonly used systemic antifungal drug, has been tested for its anti-tumor effects on basal cell carcinoma, prostate cancer, and non-small cell lung cancer. Whether itraconazole has any specific anti-tumor effect on melanoma remains unknown. However, the goal of this study is to investigate the effect of itraconazole on melanoma and to reveal some details of its underlying mechanism. In the in vivo xenograft mouse model, we find that itraconazole can inhibit melanoma growth and extend the survival of melanoma xenograft mice, compared to non-itraconazole-treated mice...
February 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28212321/therapeutic-approaches-targeting-myc-driven-prostate-cancer
#4
REVIEW
Richard J Rebello, Richard B Pearson, Ross D Hannan, Luc Furic
The transcript encoding the proto-oncogene MYC is commonly overexpressed in prostate cancer (PC). MYC protein abundance is also increased in the majority of cases of advanced and metastatic castrate-resistant PC (mCRPC). Accordingly, the MYC-directed transcriptional program directly contributes to PC by upregulating the expression of a number of pro-tumorigenic factors involved in cell growth and proliferation. A key cellular process downstream of MYC activity is the regulation of ribosome biogenesis which sustains tumor growth...
February 16, 2017: Genes
https://www.readbyqxmd.com/read/28210865/the-impact-of-melanoma-genetics-on-treatment-response-and-resistance-in-clinical-and-experimental-studies
#5
M Kunz, M Hölzel
Recent attempts to characterize the melanoma mutational landscape using high-throughput sequencing technologies have identified new genes and pathways involved in the molecular pathogenesis of melanoma. Apart from mutated BRAF, NRAS, and KIT, a series of new recurrently mutated candidate genes with impact on signaling pathways have been identified such as NF1, PTEN, IDH1, RAC1, ARID2, and TP53. Under targeted treatment using BRAF and MEK1/2 inhibitors either alone or in combination, a majority of patients experience recurrences, which are due to different genetic mechanisms such as gene amplifications of BRAF or NRAS, MEK1/2 and PI3K mutations...
February 16, 2017: Cancer Metastasis Reviews
https://www.readbyqxmd.com/read/28210516/immunohistochemical-investigation-of-her-akt-mtor-pathway-and-cellular-adhesion-molecules-in-urothelial-carcinomas
#6
Nikolaos Koletsas, Triantafyllia Koletsa, Spyros Choidas, Konstantinos Anagnostopoulos, Stavros Touloupidis, Thomas Zaramboukas, Georgia Raptou, Nikolaos Papadopoulos, Maria Lambropoulou
Background. Several investigators have suggested the possibility that the expression of both EGFR and HER2 could be utilized for molecularly targeted therapy in urinary bladder cancer. We tried to evaluate the expression of HER2 and EGFR and activation of the AKT/PTEN/mTOR pathway in urothelial carcinomas and if there is any association between them and cellular adhesion molecules (CAMs). Materials and Methods. Forty-one paraffin-embedded urothelial cancer tissue blocks were collected. Immunostains for HER2, EGFR, MIB1, phospho-AKT, PTEN, phospho-mTOR, e-cadherin, p-cadherin, and b-catenin were performed on tissue microarrays sections...
2017: Pathology Research International
https://www.readbyqxmd.com/read/28205653/phosphorylation-of-zinc-channel-zip7-drives-mapk-pi3k-and-mtor-growth-and-proliferation-signalling
#7
T Nimmanon, S Ziliotto, S Morris, L Flanagan, K M Taylor
Zinc is an essential trace element participating in diverse biological processes. Cellular zinc levels are strictly controlled by two families of transport proteins: ZIP channels (SLC39A) and ZnT transporters (SLC30A). ZIP channels increase cytosolic zinc levels by importing zinc into cells or releasing zinc from intracellular stores such as the ER. Among all the 14 human members of the ZIP family, ZIP7 is a gatekeeper of zinc release from intracellular stores, requiring post-translational activation by phosphorylation on residues S275 and S276, resulting in activation of multiple downstream pathways...
February 16, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/28205545/octreotide-attenuates-acute-kidney-injury-after-hepatic-ischemia-and-reperfusion-by-enhancing-autophagy
#8
Huiping Sun, Shuangfa Zou, Keith A Candiotti, Yanhua Peng, Qinya Zhang, Weiqiang Xiao, Yiyun Wen, Jiao Wu, Jinfeng Yang
Octreotide exerts a protective effect in hepatic ischemia-reperfusion (HIR) injury. However, whether octreotide preconditioning could also reduce acute kidney injury (AKI) after HIR is unknown. This study was designed to investigate the role of octreotide in AKI after HIR. Male Sprague-Dawley rats were pretreated with octreotide or octreotide combined with 3-methyladenine (autophagy inhibitor, 3MA). Plasma creatinine, inflammation markers (e.g., TNF-α and IL-6 etc.), apoptosis, autophagy and phosphorylation of protein kinase B/mammalian target of rapamycin/p70 ribosomal S6 kinase (Akt/mTOR/p70S6K) in the kidney were measured after 60 minutes of liver ischemia and 24 hours of reperfusion for each rat...
February 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28198538/role-of-pin1-on-in-vivo-periodontal-tissue-and-in-vitro-cells
#9
K-H Park, E-H Cho, W-J Bae, H-S Kim, H-C Lim, Y-D Park, M-O Lee, E-S Cho, E-C Kim
BACKGROUND: Although expression of peptidyl-prolyl cis/trans isomerase NIMA-interacting 1 (PIN1) was reported in bone tissue, the precise role of PIN1 in periodontal tissue and cells remain unclear. MATERIAL & METHODS: To elucidate the roles of PIN1 in periodontal tissue, its expression in periodontal tissue and cells, and effects on in vitro 4 osteoblast differentiation and the underlying signaling mechanisms were evaluated. RESULTS: PIN1 was expressed in mouse periodontal tissues including periodontal ligament cells (PDLCs), cementoblasts and osteoblasts at the developing root formation stage (postnatal, PN14) and functional stage of tooth (PN28)...
February 15, 2017: Journal of Periodontal Research
https://www.readbyqxmd.com/read/28198521/sevoflurane-ameliorates-doxorubicin-induced-myocardial-injury-by-affecting-the-phosphorylation-states-of-proteins-in-pi3k-akt-mtor-signaling-pathway
#10
Yini Wu, Jianping Wang, Xiaoyan Yu, Dongli Li, Xin Han, Lihua Fan
BACKGROUND: The effect of sevoflurane on the doxorubicin-induced myocardial injury was explored by investigating the phosphorylation states of proteins in phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway. METHODS: Myocardial injury rat models were induced by doxorubicin and evenly assigned into five groups according to different treatment: Doxorubicin group (DG, 200-µL saline solution), sevoflurane group (SevG, inhaled with 2...
February 15, 2017: Cardiology Journal
https://www.readbyqxmd.com/read/28197812/mcpip1-contributes-to-clear-cell-renal-cell-carcinomas-development
#11
Janusz Ligeza, Paulina Marona, Natalia Gach, Barbara Lipert, Katarzyna Miekus, Waclaw Wilk, Janusz Jaszczynski, Andrzej Stelmach, Agnieszka Loboda, Jozef Dulak, Wojciech Branicki, Janusz Rys, Jolanta Jura
Monocyte Chemoattractant protein-induced protein 1 (MCPIP1), also known as Regnase-1, is encoded by the ZC3H12a gene, and it mediates inflammatory processes by regulating the stability of transcripts coding for proinflammatory cytokines and controlling activity of transcription factors, such as NF-κB and AP1. We found that MCPIP1 transcript and protein levels are strongly downregulated in clear cell renal cell carcinoma (ccRCC) samples, which were derived from patients surgically treated for renal cancer compared to surrounded normal tissues...
February 14, 2017: Angiogenesis
https://www.readbyqxmd.com/read/28197628/resveratrol-induced-autophagy-and-apoptosis-in-cisplatin-resistant-human-oral-cancer-car-cells-a-key-role-of-ampk-and-akt-mtor-signaling
#12
Chao-Hsiang Chang, Chao-Ying Lee, Chi-Cheng Lu, Fuu-Jen Tsai, Yuan-Man Hsu, Je-Wei Tsao, Yu-Ning Juan, Hong-Yi Chiu, Jai-Sing Yang, Ching-Chiung Wang
Resveratrol is known to be an effective chemo-preventive phytochemical against multiple tumor cells. However, the increasing drug resistance avoids the cancer treatment in oral cavity cancer. In this study, we investigated the oral antitumor activity of resveratrol and its mechanism in cisplatin-resistant human oral cancer CAR cells. Our results demonstrated that resveratrol had an extremely low toxicity in normal oral cells and provoked autophagic cell death to form acidic vesicular organelles (AVOs) and autophagic vacuoles in CAR cells by acridine orange (AO) and monodansylcadaverine (MDC) staining...
January 30, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28196884/functional-genomics-analysis-of-vitamin-d-effects-on-cd4-t-cells-in-vivo-in-experimental-autoimmune-encephalomyelitis-%C3%A2
#13
Manuel Zeitelhofer, Milena Z Adzemovic, David Gomez-Cabrero, Petra Bergman, Sonja Hochmeister, Marie N'diaye, Atul Paulson, Sabrina Ruhrmann, Malin Almgren, Jesper N Tegnér, Tomas J Ekström, André Ortlieb Guerreiro-Cacais, Maja Jagodic
Vitamin D exerts multiple immunomodulatory functions and has been implicated in the etiology and treatment of several autoimmune diseases, including multiple sclerosis (MS). We have previously reported that in juvenile/adolescent rats, vitamin D supplementation protects from experimental autoimmune encephalomyelitis (EAE), a model of MS. Here we demonstrate that this protective effect associates with decreased proliferation of CD4+ T cells and lower frequency of pathogenic T helper (Th) 17 cells. Using transcriptome, methylome, and pathway analyses in CD4+ T cells, we show that vitamin D affects multiple signaling and metabolic pathways critical for T-cell activation and differentiation into Th1 and Th17 subsets in vivo...
February 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28195449/effects-of-resveratrol-on-the-expression-of-molecules-related-to-the-mtor-signaling-pathway-in-pathological-scar-fibroblasts
#14
Zhiming Tang, Ji-Cun Ding, Xiao-Xiang Zhai
BACKGROUND: We observed the effects of resveratrol on the expression of molecules involved in the mTOR signaling pathway in pathological scar fibroblasts, including PI3K, Akt and mTOR. METHODS: We detected the expression of PI3K, Akt and mTOR in pathological scar and normal skin fibroblasts through immunofluorescence. After being treated with different concentrations of resveratrol, the expression of PI3K, Akt and mTOR mRNA and protein were detected by RT-PCR and Western Blot respectively...
February 14, 2017: Giornale Italiano di Dermatologia e Venereologia: Organo Ufficiale, Società Italiana di Dermatologia e Sifilografia
https://www.readbyqxmd.com/read/28193689/signaling-by-fgf-receptor-2-not-fgf-receptor-1-regulates-myelin-thickness-through-activation-of-erk1-2-mapk-which-promotes-mtorc1-activity-in-an-akt-independent-manner
#15
M Furusho, A Ishii, R Bansal
FGF signaling has emerged as a significant 'late-stage' regulator of myelin thickness in the CNS, independent of oligodendrocyte differentiation. Therefore, it is critically important to identify the specific FGF-Receptor-type and its downstream signaling molecules in oligodendrocytes to obtain better insights into the regulatory mechanisms of myelin growth. Here, we show that FGF-Receptor-type-2 (FGFR2) is highly enriched at the paranodal loops of myelin. Conditional ablation of this receptor-type, but not FGF-Receptor-type-1 (FGFR1), resulted in attenuation of myelin growth, expression of major myelin genes, key transcription factor Myrf and ERK1/2 activity...
February 13, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28193579/zinc-enhances-intestinal-epithelial-barrier-function-through-the-pi3k-akt-mtor-signaling-pathway-in-caco-2-cells
#16
Yuxin Shao, Patricia G Wolf, Shuangshuang Guo, Yuming Guo, H Rex Gaskins, Bingkun Zhang
Zinc plays an important role in maintaining intestinal barrier function as well as modulating cellular signaling recognition and protein kinase activities. The phosphatidylinositol 3-kinase (PI3K) cascade has been demonstrated to affect intercellular integrity and tight junction (TJ) proteins. The current study investigated the hypothesis that zinc regulates intestinal intercellular junction integrity through the PI3K/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway. A transwell model of Caco-2 cell was incubated with 0, 50 and 100 μM of zinc at various time points...
January 31, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28193525/caffeic-acid-phenethyl-ester-attenuates-liver-fibrosis-via-inhibition-of-tgf-%C3%AE-1-smad3-pathway-and-induction-of-autophagy-pathway
#17
Ning Yang, Shuangsuo Dang, Juanjuan Shi, Fengping Wu, Mei Li, Xin Zhang, Yaping Li, Xiaoli Jia, Song Zhai
Caffeic acid phenethyl ester (CAPE) has been reported to possess the hepatoprotective effect. This study was to investigate the mechanism underlying CAPE against liver fibrosis in a liver fibrosis model induced by toxic carbon tetrachloride (CCl4) in male Sprague-Dawley rats and in vitro in CAPE (5 μM, 10 μM, 15 μM) treated hepatic stellate cells (HSC-T6). We found that CAPE treatment remarkably attenuated CCl4-induced liver fibrosis by blocking the activation of HSCs as determined by the expression alternation of transforming growth factor (TGF)-β1, phosphorylated Smad3 (p-Smad3), collage I, α-smooth muscle actin (α-SMA), matrix metalloproteinases (MMPs) 2, tissue inhibitor of matrix metalloproteinases (TIMPs) 1...
February 10, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28192480/mtor-activity-in-aids-related-diffuse-large-b-cell-lymphoma
#18
Sara H Browne, Julio A Diaz-Perez, Michael Preziosi, Charles C King, George A Jones, Sonia Jain, Xiaoying Sun, Erin G Reid, Scott VandenBerg, Huan-You Wang
BACKGROUND: Patients infected with HIV have a significantly increased risk of developing non-Hodgkin lymphomas despite the widespread use of HAART. To investigate mTOR pathway activity in acquired immunodeficiency syndrome (AIDS) related diffuse large B-cell lymphoma AR-DLBCL, we used immunohistochemistry to examine the presence of the phosphorylated 70 ribosomal S6 protein-kinase (p70S6K), an extensively studied effector of mTOR Complex 1 (mTORC1) and the phosphorylated phosphatase and tensin homolog (pPTEN), a negative regulator of mTORC1 pathway...
2017: PloS One
https://www.readbyqxmd.com/read/28192408/macrophages-confer-survival-signals-via-ccr1-dependent-translational-mcl-1-induction-in-chronic-lymphocytic-leukemia
#19
M H A van Attekum, S Terpstra, E Slinger, M von Lindern, P D Moerland, A Jongejan, A P Kater, E Eldering
Protective interactions with bystander cells in micro-environmental niches, such as lymph nodes (LNs), contribute to survival and therapy resistance of chronic lymphocytic leukemia (CLL) cells. This is caused by a shift in expression of B-cell lymphoma 2 (BCL-2) family members. Pro-survival proteins B-cell lymphoma-extra large (BCL-XL), BCL-2-related protein A1 (BFL-1) and myeloid leukemia cell differentiation protein 1 (MCL-1) are upregulated by LN-residing T cells through CD40L interaction, presumably via nuclear factor (NF)-κB signaling...
February 13, 2017: Oncogene
https://www.readbyqxmd.com/read/28191279/ros-dependent-activation-of-autophagy-through-the-pi3k-akt-mtor-pathway-is-induced-by-hydroxysafflor-yellow-a-sonodynamic-therapy-in-thp-1-macrophages
#20
Yueqing Jiang, Jiayuan Kou, Xiaobo Han, Xuesong Li, Zhaoyu Zhong, Zhongni Liu, Yinghong Zheng, Ye Tian, Liming Yang
Monocyte-derived macrophages participate in infaust inflammatory responses by secreting various types of proinflammatory factors, resulting in further inflammatory reactions in atherosclerotic plaques. Autophagy plays an important role in inhibiting inflammation; thus, increasing autophagy may be a therapeutic strategy for atherosclerosis. In the present study, hydroxysafflor yellow A-mediated sonodynamic therapy was used to induce autophagy and inhibit inflammation in THP-1 macrophages. Following hydroxysafflor yellow A-mediated sonodynamic therapy, autophagy was induced as shown by the conversion of LC3-II/LC3-I, increased expression of beclin 1, degradation of p62, and the formation of autophagic vacuoles...
2017: Oxidative Medicine and Cellular Longevity
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