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Phospho-AKT

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https://www.readbyqxmd.com/read/28300578/cellular-interactions-of-the-phosphorylated-form-of-akt-in-prostate-cancer
#1
Kai H Hammerich, Anna Frolov, Rile Li, Michael Ittmann, Gustavo E Ayala
Phospho-Akt (P-Akt1) promotes proliferation and increased survival in vitro and plays an important role in prostate cancer (PCa) progression as well as the prediction of the probability of recurrence. In this study, the goal was to demonstrate the involvement and impact of P-Akt1 on cellular interactions, biomechanisms and pathways in PCa. Tissue microarrays from 640 PCa patients were immunostained with various antibodies. Ki67 was used to measure proliferation index and Tunnel for apoptotic index. Increased expression of P-Akt1 was associated with an increased proliferation, but inversely correlated with apoptotic index...
March 11, 2017: Human Pathology
https://www.readbyqxmd.com/read/28289208/specific-deletion-of-lkb1-stk11-in-the-m%C3%A3-llerian-duct-mesenchyme-drives-hyperplasia-of-the-periurethral-stroma-and-tumorigenesis-in-male-mice
#2
Jitu W George, Amanda L Patterson, Pradeep S Tanwar, André Kajdacsy-Balla, Gail S Prins, Jose M Teixeira
Nearly all older men will experience lower urinary tract symptoms associated with benign prostatic hyperplasia (BPH), the etiology of which is not well understood. We have generated Stk11(CKO) mice by conditional deletion of the liver kinase B1 (LKB1) tumor suppressor gene, Stk11 (serine threonine kinase 11), in the fetal Müllerian duct mesenchyme (MDM), the caudal remnant of which is thought to be assimilated by the urogenital sinus primordial mesenchyme in males during fetal development. We show that MDM cells contribute to the postnatal stromal cells at the dorsal aspect of the prostatic urethra by lineage tracing...
March 13, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28288548/upregulated-glutathione-transferase-omega-1-correlates-with-progression-of-urinary-bladder-carcinoma
#3
Tatjana Djukic, Tatjana Simic, Marija Pljesa-Ercegovac, Marija Matic, Sonja Suvakov, Vesna Coric, Dejan Dragicevic, Ana Savic-Radojevic
OBJECTIVES: Newly discovered glutathione transferase omega 1 (GSTO1-1) plays an important role in the glutathionylation cycle, a significant mechanism of protein function regulation. GSTO1-1 expression pattern has not been studied in transitional cell carcinoma (TCC), as yet. METHODS: A total of 56 TCC tumor and corresponding non-tumor specimens were investigated. Glutathione content and thioltransferase activity were measured spectrophotometrically. Protein-glutathione mixed disulfides were measured fluorimetrically...
March 13, 2017: Redox Report: Communications in Free Radical Research
https://www.readbyqxmd.com/read/28285180/noninvasive-bioluminescence-imaging-of-akt-kinase-activity-in-subcutaneous-and-orthotopic-nsclc-xenografts-correlation-of-akt-activity-with-tumor-growth-kinetics
#4
Karina Suchowski, Thomas Pöschinger, Alnawaz Rehemtulla, Michael Stürzl, Werner Scheuer
Aberrant signaling through the AKT kinase mediates oncogenic phenotypes including cell proliferation, survival, and therapeutic resistance. Here, we utilize a bioluminescence reporter for AKT kinase activity (BAR) to noninvasively assess the therapeutic efficacy of the EGFR inhibitor erlotinib in KRAS-mutated lung cancer therapy. A549 non-small cell lung cancer cell line, engineered to express BAR, enabled the evaluation of compounds targeting the EGFR/PI3K/AKT pathway in vitro as well as in mouse models. We found that erlotinib treatment of resistant A549 subcutaneous and orthotopic xenografts resulted in significant AKT inhibition as determined by an 8- to 13-fold (P < ...
March 9, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28281841/lncrna-nonratt021972-sirna-normalized-the-dysfunction-of-hepatic-glucokinase-through-akt-signaling-in-t2dm-rats
#5
Miaomiao Song, Lifang Zou, Lichao Peng, Shuangmei Liu, Bing Wu, Zhihua Yi, Yun Gao, Chunping Zhang, Hong Xu, Yurong Xu, Mengxia Tang, Shouyu Wang, Yun Xue, Tianyu Jia, Shanhong Zhao, Shangdong Liang, Guilin Li
Hepatic glucokinase (GK) expression and activity are decreased in type 2 diabetes mellitus (T2DM), and glycogen synthase kinase-3 (GSK-3) inhibits the synthesis of GK. In hepatocytes, the activation of the protein kinase B (PKB/AKT) signaling pathway enhances GK expression and inhibits the phosphorylation of GSK-3β. The dysfunction of certain long noncoding RNAs (lncRNAs) has been associated with a variety of diseases. AIMS: This study explored the effects of the lncRNA NONRATT021972 small interfering RNA (siRNA) on the dysfunction of hepatic GK through AKT signaling in T2DM rats...
March 10, 2017: Endocrine Research
https://www.readbyqxmd.com/read/28281555/nf-%C3%AE%C2%BAb-p50-activation-associated-with-immune-dysregulation-confers-poorer-survival-for-diffuse-large-b-cell-lymphoma-patients-with-wild-type-p53
#6
Qingqing Cai, Meifeng Tu, Zijun Y Xu-Monette, Ruifang Sun, Ganiraju C Manyam, Xiaolu Xu, Alexander Tzankov, Eric D Hsi, Michael B Møller, L Jeffrey Medeiros, Chi Young Ok, Ken H Young
Dysregulated NF-κB signaling is critical for lymphomagenesis, however, the expression and clinical relevance of NF-κB subunit p50 in diffuse large B-cell lymphoma have not been evaluated. In this study, we analyzed the prognostic significance and gene expression signatures of p50 nuclear expression as a surrogate for p50 activation in 465 patients with de novo diffuse large B-cell lymphoma. We found that p50(+) nuclear expression, observed in 34.6% of diffuse large B-cell lymphoma, predominantly composed of activated B-cell-like subtype, was an independent adverse prognostic factor in patients with activated B-cell-like diffuse large B-cell lymphoma...
March 10, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28276427/trib2-confers-resistance-to-anti-cancer-therapy-by-activating-the-serine-threonine-protein-kinase-akt
#7
Richard Hill, Patricia A Madureira, Bibiana Ferreira, Inês Baptista, Susana Machado, Laura Colaço, Marta Dos Santos, Ningshu Liu, Ana Dopazo, Selma Ugurel, Angyal Adrienn, Endre Kiss-Toth, Murat Isbilen, Ali O Gure, Wolfgang Link
Intrinsic and acquired resistance to chemotherapy is the fundamental reason for treatment failure for many cancer patients. The identification of molecular mechanisms involved in drug resistance or sensitization is imperative. Here we report that tribbles homologue 2 (TRIB2) ablates forkhead box O activation and disrupts the p53/MDM2 regulatory axis, conferring resistance to various chemotherapeutics. TRIB2 suppression is exerted via direct interaction with AKT a key signalling protein in cell proliferation, survival and metabolism pathways...
March 9, 2017: Nature Communications
https://www.readbyqxmd.com/read/28271613/qiliqiangxin-protects-against-anoxic-injury-in-cardiac-microvascular-endothelial-cells-via-nrg-1-erbb-pi3k-akt-mtor-pathway
#8
Jingfeng Wang, Jingmin Zhou, Yanyan Wang, Chunjie Yang, Mingqiang Fu, Jingjing Zhang, Xueting Han, Zhiming Li, Kai Hu, Junbo Ge
Cardiac microvascular endothelial cells (CMECs) are important angiogenic components and are injured rapidly after cardiac ischaemia and anoxia. Cardioprotective effects of Qiliqiangxin (QL), a traditional Chinese medicine, have been displayed recently. This study aims to investigate whether QL could protect CMECs against anoxic injury and to explore related signalling mechanisms. CMECs were successfully cultured from Sprague-Dawley rats and exposed to anoxia for 12 hrs in the absence and presence of QL. Cell migration assay and capillary-like tube formation assay on Matrigel were performed, and cell apoptosis was determined by TUNEL assay and caspase-3 activity...
March 8, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28237545/enhancement-of-brain-plasticity-and-recovery-of-locomotive-function-after-lumbar-spinal-cord-stimulation-in-combination-with-gait-training-with-partial-weight-support-in-rats-with-cerebral-ischemia
#9
Yoon-Hee Choi, Shi-Uk Lee
Lumbar spinal cord stimulation (LSCS) is reportedly effective for the recovery of locomotive intraspinal neural network, motor cortex and basal ganglia in animals with complete spinal cord injury and parkinsonism. We evaluated the effect of LSCS in combination with gait training on the recovery of locomotive function and brain plasticity using a rat model of brain ischemia. Adult male Sprague Dawley rats with ischemia were randomly assigned into one of four groups: sham treatment (group 1), LSCS only (group 2), LSCS with gait training and 50% (group 3) and 80% (group 4) of body weight support...
February 22, 2017: Brain Research
https://www.readbyqxmd.com/read/28222424/1%C3%AE-25-oh-2d3-sensitive-cytosolic-ph-regulation-and-glycolytic-flux-in-human-endometrial-ishikawa-cells
#10
Ni Zeng, Yuetao Zhou, Shaqiu Zhang, Yogesh Singh, Bing Shi, Madhuri S Salker, Florian Lang
BACKGROUND/AIMS: Tumor cell proliferation is modified by 1,25-Dihydroxy-Vitamin D3 (1,25(OH)2D3), a steroid hormone predominantly known for its role in calcium and phosphorus metabolism. Key properties of tumor cells include enhanced glycolytic flux with excessive consumption of glucose and formation of lactate. As glycolysis is highly sensitive to cytosolic pH, maintenance of glycolysis requires export of H+ ions and lactate, which is in part accomplished by Na+/H+ exchangers, such as NHE1 and monocarboxylate transporters, such as MCT4...
February 8, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28210516/immunohistochemical-investigation-of-her-akt-mtor-pathway-and-cellular-adhesion-molecules-in-urothelial-carcinomas
#11
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/28209758/atorvastatin-decreases-hbx-induced-phospho-akt-in-hepatocytes-via-p2x-receptors
#12
Aram Ghalali, Javier Martin-Renedo, Johan Hogberg, Ulla Stenius
Hepatocellular carcinoma (HCC) is rated as the fifth most common malignancy and third in cancer related deaths worldwide. Statins, HMG-CoA reductase inhibitors, are potent cholesterol lowering drugs and recent epidemiological evidence suggests that statins prevent aggressive HCC development. Previous experiments revealed that statins downregulate phosphorylated Akt (pAkt). Here, it is demonstrated that atorvastatin decreases nuclear pAkt levels in pancreatic and lung cancer cell lines within minutes and this rapid effect is mediated by the purinergic P2X receptors...
February 16, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28202289/rolipram-potentiates-bevacizumab-induced-cell-death-in-human-glioblastoma-stem-like-cells
#13
Sara Ramezani, Nasim Vousooghi, Fatemeh Ramezani Kapourchali, Mahmoudreza Hadjighasem, Parisa Hayat, Naser Amini, Mohammad Taghi Joghataei
AIMS: Glioblastoma cancer stem-like cells (GCSCs) promote themselves proliferation by secreting the vascular endothelial growth factor A (VEGFA) in an autocrine manner, positively regulated by phosphodiesterase IV (PDE4). In the current study, we investigated the putative cytotoxic effect of bevacizumab, a VEGFA blocker, alone and in combination with a specific inhibitor of PDE4 called rolipram on GCSCs isolated from human surgical tumor specimen with a focus on PI3K/AKT pathway. MAIN METHODS: CD133+/CD15+ GCSCs were characterized by flow cytometry and expanded in a serum-free primary culture system...
March 15, 2017: Life Sciences
https://www.readbyqxmd.com/read/28199187/combinatorial-effect-of-curcumin-with-docetaxel-modulates-apoptotic-and-cell-survival-molecules-in-prostate-cancer
#14
Saswati Banerjee, Santosh K Singh, Indrajit Chowdhury, Rajesh Singh
Docetaxel is the most commonly used chemotherapeutic agent to target androgen signaling in metastatic prostate cancer (PCa); however, prolonged treatment with docetaxel results in drug-resistant cancer cells. Combination therapies have the potential of increasing the effectiveness of drug treatment as well as decreasing the side effects. Curcumin is a nontoxic organic compound with multifaceted chemopreventive potential. In this study, we evaluated whether curcumin can reinforce the effect of docetaxel on PCa cells...
March 1, 2017: Frontiers in Bioscience (Elite Edition)
https://www.readbyqxmd.com/read/28196852/inpp4b-and-pten-loss-leads-to-pi-3-4-p2-accumulation-and-inhibition-of-pi3k-in-tnbc
#15
Darien E Reed, Kevan M Shokat
Triple-negative breast cancer [TNBC, lacks expression of estrogen receptor (ER), progesterone receptor (PR) and amplification of HER2/Neu] remains one of the most aggressive subtypes, affects the youngest patients and still lacks an effective targeted therapy(1,2). Both phosphatidylinositol-3-kinase (PI3K)-α and -β contribute to oncogenesis of solid tumors, including the development of breast cancer(3). Inositol polyphosphate-4-phosphatase type II (INPP4B) catalyzes the removal of the 4'-phosphate of phosphatidylinositol-(3,4-bisphosphate (PI-3,4-P2) creating phosphatidylinositol-3-phosphate(4)...
February 14, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28193719/brain-specific-ablation-of-efr3a-promotes-adult-hippocampal-neurogenesis-via-the-brain-derived-neurotrophic-factor-pathway
#16
Qi Qian, Qiuji Liu, Dongming Zhou, Hongyu Pan, Zhiwei Liu, Fangping He, Suying Ji, Dongpi Wang, Wangxiao Bao, Xinyi Liu, Zhaoling Liu, Heng Zhang, Xiaoqin Zhang, Ling Zhang, Mingkai Wang, Ying Xu, Fude Huang, Benyan Luo, Binggui Sun
Efr3 is a newly identified plasma membrane protein and plays an important role in the phosphoinositide metabolism on the plasma membrane. However, although it is highly expressed in the brain, the functional significance of Efr3 in the brain is not clear. In the present study, we generated Efr3a(f/f) mice and then crossed them with Nestin-Cre mice to delete Efr3a, one of the Efr3 isoforms, specifically in the brain. We found that brain-specific ablation of Efr3a promoted adult hippocampal neurogenesis by increasing survival and maturation of newborn neurons without affecting their dendritic tree morphology...
February 13, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28186985/mir-124-3p-attenuates-hyperphosphorylation-of-tau-protein-induced-apoptosis-via-caveolin-1-pi3k-akt-gsk3%C3%AE-pathway-in-n2a-app695swe-cells
#17
Qingmei Kang, Yue Xiang, Dan Li, Jie Liang, Xiong Zhang, Fanlin Zhou, Mengyuan Qiao, Yingling Nie, Yurong He, Jingyi Cheng, Yubing Dai, Yu Li
Hyperphosphorylation of Tau forming neurofibrillary tangles has been considered as a crucial event in the pathogenesis of Alzheimer's disease (AD). MiR-124-3p belongs to microRNA (miRNA) family and was markedly decreased in AD, however, the functions of miR-124-3p in the pathogenesis of AD remain unknown. We observed that the expression of miR-124-3p was significantly decreased in N2a/APP695swe cells; and transfection of miR-124-3p mimics not only attenuated cell apoptosis and abnormal hyperphosphorylation of Tau protein without any changes of total Tau protein, but also increased expression levels of Caveolin-1, phosphoinositide 3-kinase (PI3K), phospho-Akt (Akt-Ser473)/Akt, phospho-glycogen synthase kinase-3 beta (GSK-3β-Ser9)/GSK-3β in N2a/APP695swe cells...
February 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28185837/insulin-promotes-her2-signaling-activation-during-barrett-s-esophagus-carcinogenesis
#18
Diletta Arcidiacono, Alessandro Antonello, Matteo Fassan, Daniele Nucci, Tiziana Morbin, Marco Agostini, Donato Nitti, Massimo Rugge, Alfredo Alberti, Giorgio Battaglia, Stefano Realdon
BACKGROUND: Insulin-resistance and hyperinsulinemia could have a role in the growing incidence of esophageal adenocarcinoma (EAC) and its pre-cancerous lesion Barrett's Esophagus (BE). HER2 activation has also a pivotal role in EAC carcinogenesis but no data correlate these two phenomena in this disease context. AIMS: To investigate the role of hyperinsulinemia in BE-dysplasia-adenocarcinoma sequence and the possible relationship between insulin-mediated and HER2 signaling in EAC development...
January 22, 2017: Digestive and Liver Disease
https://www.readbyqxmd.com/read/28184930/resveratrol-enhances-the-radiosensitivity-of-nasopharyngeal-carcinoma-cells-by-downregulating-e2f1
#19
Yuhui Tan, Xianli Wei, Wenyin Zhang, Xiaolan Wang, Kun Wang, Biaoyan Du, Jianyong Xiao
Identification of safe, effective radiosensitizing agents is urgently needed to improve the outcome of radiotherapy in nasopharyngeal cancer (NPC). In this study, we assessed the ability of the polyphenol resveratrol to act as a radiosensitizer in vitro and in vivo. CNE-1 cells were treated with 50 µM resveratrol for 24 h, then irradiated. E2F transcription factor 1 (E2F1) was stably knocked down and overexpressed using lentiviruses. A xenograft model of NPC was established in nude mice using CNE-1 cells...
March 2017: Oncology Reports
https://www.readbyqxmd.com/read/28176796/depurinized-milk-downregulates-rat-thymus-myd88-akt-p38-function-nf-%C3%AE%C2%BAb-mediated-inflammation-caspase-1-activity-but-not-the-endonuclease-pathway-in-vitro-in-vivo-study
#20
Gordana Kocic, Andrej Veljkovic, Hristina Kocic, Miodrag Colic, Dusan Mihajlovic, Katarina Tomovic, Svetlana Stojanovic, Andrija Smelcerovic
The aim of this study was the evaluation of 15 days dietary regimen of depurinized (DP) milk (obtained using our patented technological procedures) or 1.5% fat UHT milk instead of standard chow diet, on rat thymus and bone marrow MyD88/Akt/p38, NF-κB, caspase-1 and endonuclease pathways, in relation to peripheral blood cell composition. To determine whether the reduced mass of the thymus is a consequence of the direct effect of DP/UHT milk on apoptosis of thymocytes, in vitro Annexin-V-FITC/PI assay was performed...
February 8, 2017: Scientific Reports
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