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PI3K/AKT

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https://www.readbyqxmd.com/read/27923043/clonal-evolutionary-analysis-during-her2-blockade-in-her2-positive-inflammatory-breast-cancer-a-phase-ii-open-label-clinical-trial-of-afatinib-vinorelbine
#1
Gerald Goh, Ramona Schmid, Kelly Guiver, Wichit Arpornwirat, Imjai Chitapanarux, Vinod Ganju, Seock-Ah Im, Sung-Bae Kim, Arunee Dechaphunkul, Jedzada Maneechavakajorn, Neil Spector, Thomas Yau, Mehdi Afrit, Slim Ben Ahmed, Stephen R Johnston, Neil Gibson, Martina Uttenreuther-Fischer, Javier Herrero, Charles Swanton
BACKGROUND: Inflammatory breast cancer (IBC) is a rare, aggressive form of breast cancer associated with HER2 amplification, with high risk of metastasis and an estimated median survival of 2.9 y. We performed an open-label, single-arm phase II clinical trial (ClinicalTrials.gov NCT01325428) to investigate the efficacy and safety of afatinib, an irreversible ErbB family inhibitor, alone and in combination with vinorelbine in patients with HER2-positive IBC. This trial included prospectively planned exome analysis before and after afatinib monotherapy...
December 2016: PLoS Medicine
https://www.readbyqxmd.com/read/27922821/identification-of-salvia-haenkei-as-gerosuppressant-agent-by-using-an-integrated-senescence-screening-assay
#2
Ivana Matic, Ajinkya Revandkar, Jingjing Chen, Angela Bisio, Stefano Dall'Acqua, Veronica Cocetta, Paola Brun, Giorgio Mancino, Martina Milanese, Maurizio Mattei, Monica Montopoli, Andrea Alimonti
Cellular senescence is a stable cell cycle arrest that is the causative process of aging. The PI3K/AKT/mTOR pathway is implicated in the control of cellular senescence and inhibitors of this pathway have been successfully used for life span prolongation experiments in mammals. PTEN is the major regulator of the PI3K/AKT/mTOR pathway and loss of PTEN promotes a senescence response termed PICS. Here we report a novel-screening assay, for the identification of compounds that block different types of senescence response...
December 1, 2016: Aging
https://www.readbyqxmd.com/read/27922691/microarray-expression-profiles-of-genes-in-lung-tissues-of-rats-subjected-to-focal-cerebral-ischemia-induced-lung-injury-following-bone-marrow-derived-mesenchymal-stem-cell-transplantation
#3
Yue Hu, Liu-Lin Xiong, Piao Zhang, Ting-Hua Wang
Ischemia-induced stroke is the most common disease of the nervous system and is associated with a high mortality rate worldwide. Cerebral ischemia may lead to remote organ dysfunction, particular in the lungs, resulting in lung injury. Nowadays, bone marrow-derived mesenchymal stem cells (BMSCs) are widely studied in clinical trials as they may provide an effective solution to the treatment of neurological and cardiac diseases; however, the underlying molecular mechanisms remain unknown. In this study, a model of permanent focal cerebral ischemia-induced lung injury was successfully established and confirmed by neurological evaluation and lung injury scores...
December 6, 2016: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/27920883/exogenous-secreted-frizzled-related-protein-4-modulates-steroidogenesis-of-rat-granulosa-cells-through-wnt-%C3%AE-catenin-and-pi3k-akt-signaling-pathways
#4
Ghamartaj Hossein, Manijeh Khanmohammadi, Parisa Sahranavard Fard, Yasaman Heidarian, Somaieh Kazemnejad, Mohammad Mehdi Akhondi
BACKGROUND: It has been reported that secreted frizzled-related protein-4 known as an antagonist of Wnt signaling pathway plays a role in luteinization process of rodent granulosa cells. The purpose of this study was twofold: 1) to determine whether recombinant human secreted frizzled-related protein-4 (rhSFRP-4) could directly induce terminal differentiation of rat Granulosa Cells (GCs) and 2) to understand how the modulation of β-catenin and Protein Kinase B (PKB)/AKT activity by exogenous SFRP-4 could be involved in steroidogenesis...
October 2016: Avicenna Journal of Medical Biotechnology
https://www.readbyqxmd.com/read/27919945/the-leloir-pathway-of-galactose-metabolism-a-novel-therapeutic-target-for-hepatocellular-carcinoma
#5
Manshu Tang, Enoabasi Etokidem, Kent Lai
Hepatocellular carcinoma (HCC) is one of the most lethal types of cancer worldwide, with poor prognosis and limited treatments. In order to identify novel therapeutic targets that will lead to development of effective therapies with manageable side effects, we tested the hypothesis that knocking-down galactokinase (GALK1) or galactose-1 phosphate uridylyltransferase (GALT) gene expression would control the growth of cultured hepatoma cells. Our results showed small interfering RNA (siRNA) against GALK1 or GALT inhibited the growth of HepG2 cells in culture...
December 2016: Anticancer Research
https://www.readbyqxmd.com/read/27919797/maximising-the-potential-of-akt-inhibitors-as-anti-cancer-treatments
#6
REVIEW
Jessica S Brown, Udai Banerji
PI3K/AKT signalling is commonly disrupted in human cancers, with AKT being a central component of the pathway, influencing multiple processes that are directly involved in tumourigenesis. Targeting AKT is therefore a highly attractive anti-cancer strategy with multiple AKT inhibitors now in various stages of clinical development. In this review, we summarise the role and regulation of AKT signalling in normal cellular physiology. We highlight the mechanisms by which AKT signalling can be hyperactivated in cancers and discuss the past, present and future clinical strategies for AKT inhibition in oncology...
December 2, 2016: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/27919735/quercetin-attenuates-high-fructose-feeding-induced-atherosclerosis-by-suppressing-inflammation-and-apoptosis-via-ros-regulated-pi3k-akt-signaling-pathway
#7
Xue-Li Lu, Cui-Hua Zhao, Xin-Liang Yao, Han Zhang
Quercetin is a dietary flavonoid compound extracted from various plants, such as apple and onions. Previous studies have revealed its anti-inflammatory, anti-cancer, antioxidant and anti-apoptotic activities. This study investigated the ability of quercetin to inhibit high fructose feeding- or LPS-induced atherosclerosis through regulating oxidative stress, apoptosis and inflammation response in vivo and in vitro experiments. 50 and 100mg/kg quercetin were used in our study, showing significant inhibitory role in high fructose-induced atherosclerosis via reducing reactive oxygen species (ROS) levels, Caspase-3 activation, inflammatory cytokines releasing, the number of terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL)-positive cells and collagen contents as well as modulating apoptosis- and inflammation-related proteins expression...
December 2, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27919568/all-trans-retinoic-acid-suppresses-the-adhering-ability-of-arpe-19-cells-via-mitogen-activated-protein-kinase-and-focal-adhesion-kinase
#8
Yo-Chen Chang, Yuh-Shin Chang, Ming-Chu Hsieh, Horng-Jiun Wu, Meng-Hsien Wu, Chia-Wei Lin, Wen-Chuan Wu, Ying-Hsien Kao
This study investigated the signaling mechanism underlying the anti-adhesive effect of all-trans retinoic acid (ATRA) on retinal pigment epithelial ARPE-19 cells. Adhesion kinetics with or without ATRA treatment were profiled by adhesion assay. Surface coating with type IV collagen, fibronectin, laminin, but not type I collagen, significantly enhanced adhesion and spreading of ARPE-19 cells, while ATRA at subtoxic doses (ranging from 10(-7) to 10(-6) M) profoundly suppressed the extracellular matrix-enhanced adhesion ability...
November 16, 2016: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/27919208/is-metformin-a-therapeutic-paradigm-for-colorectal-cancer-insight-into-the-molecular-pathway
#9
Zar Chii Thent, Nurul Hannim Zaidun, Fairuz Azmi, Mu Izuddin Senin, Haszianaliza Haslan, Ahmad Ruzain Salehuddin
Colorectal cancer (CRC) remains one of the major leading causes of cancer related morbidity and mortality. Apart from the conventional anti-neoplastic agents, metformin, a biguanide anti-diabetic agent, has recently found to have anti-cancer property. Several studies observed the effect of metformin towards its anti-cancer effect on colon or colorectal cancer in diabetic patients. However, only a few studies showed its effect on colorectal cancer in relation to the non-diabetic status. The present review aimed to highlight the insight into the molecular pathway of metformin towards colorectal cancer in the absence of diabetes mellitus...
December 5, 2016: Current Drug Targets
https://www.readbyqxmd.com/read/27918554/asic1a-mediates-the-drug-resistance-of-human-hepatocellular-carcinoma-via-the-ca-2-pi3-kinase-akt-signaling-pathway
#10
Yihao Zhang, Ting Zhang, Chao Wu, Quan Xia, Dujuan Xu
Chemotherapy is the main treatment method of patients with advanced liver cancer. However, drug resistance is a serious problem in the treatment of hepatocellular carcinoma (HCC). Acid sensing ion channel 1a (ASIC1a) is a H(+)-gated cation channel; it mediates tumor cell migration and invasion, which suggests that it is involved in the development of malignant tumors. Therefore, we studied the relationship between ASIC1a and drug resistance in human hepatocellular carcinoma. In our study, we found that ASIC1a is highly expressed in human HCC tissue, and that its levels were significantly increased in resistant HCC cells Bel7402/FU and HepG2/ADM...
December 5, 2016: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/27918278/pi3-kinase-cascade-has-a-differential-role-in-acquisition-and-extinction-of-conditioned-fear-memory-in-juvenile-and-adult-rats
#11
Ilana Slouzkey, Mouna Maroun
The basolateral amygdala (BLA), medial prefrontal cortex (mPFC) circuit, plays a crucial role in acquisition and extinction of fear memory. Extinction of aversive memories is mediated, at least in part, by the phosphoinositide-3 kinase (PI3K)/Akt pathway in adult rats. There is recent interest in the neural mechanisms that mediate fear and extinction in juvenile animals and whether these mechanisms are distinctive from those in adult animals. In the present study, we examined (1) changes in phosphorylation of Akt in the BLA and mPFC after fear conditioning and extinction in juvenile and adult rats and (2) the effect of BLA and mPFC localized inhibition of the PI3K following acquisition and extinction of contextual fear memory...
December 2016: Learning & Memory
https://www.readbyqxmd.com/read/27918216/s100p-is-overexpressed-in-squamous-cell-and-adenosquamous-carcinoma-subtypes-of-endometrial-cancer-and-promotes-cancer-cell-proliferation-and-invasion
#12
Hongfei Jiang, Hang Hu, Fan Lin, Yoon Pin Lim, Yunfen Hua, Xiaomei Tong, Songying Zhang
S100P is known to affect tumor development and metastasis of various cancers, but its role in endometrial cancer is unclear. We reported that S100P expression was dramatically elevated in both endometrial squamous cell carcinoma and adenosquamous carcinoma, but not in adenocarcinoma and normal endometrial samples. Moreover, we revealed an oncogenic role of S100P promoting cell proliferation, invasion, and migration while reducing apoptosis, possibly via its upregulation and/or activation of receptors of advanced glycation end products and consequently the oncogenic PI3K-AKT and MAPK pathways...
November 25, 2016: Cancer Investigation
https://www.readbyqxmd.com/read/27916377/tetrahydrocurcumin-provides-neuroprotection-in-rats-after-traumatic-brain-injury-autophagy-and-the-pi3k-akt-pathways-as-a-potential-mechanism
#13
Yongyue Gao, Jie Li, Lingyun Wu, Chenhui Zhou, Qiang Wang, Xiang Li, Mengliang Zhou, Handong Wang
BACKGROUND: Tetrahydrocurcumin provides neuroprotection in multiple neurologic disorders by modulating oxidative stress, inflammatory responses, and autophagy. However, in traumatic brain injury (TBI), it is unclear whether a beneficial effect of tetrahydrocurcumin exists. In this study, we hypothesized that administration of tetrahydrocurcumin provides neuroprotection in a rat model of TBI. MATERIAL AND METHODS: Behavioral studies were performed by recording and analyzing beam-walking scores...
November 2016: Journal of Surgical Research
https://www.readbyqxmd.com/read/27916117/specific-mixing-facilitates-the-comparative-quantification-of-phosphorylation-sites-with-significant-dysregulations
#14
Jing Liu, Bo Xu, Zheyi Liu, Mingming Dong, Jiawei Mao, Ye Zhou, Jin Chen, Fangjun Wang, Hanfa Zou
Mass spectrometry (MS) based quantitative analyses of proteome and proteome post-translational modifications (PTMs) play more and more important roles in biological, pharmaceutical and clinical studies. However, it is still a big challenge to accurately quantify the proteins or proteins PTM sites with extreme relative abundances in comparative protein samples, such as the significantly dysregulated ones. Herein, a novel quantification strategy, Mixing at Specific Ratio (MaSR) before isotope labeling, had been developed to improve the quantification accuracy and coverage of extreme proteins and protein phosphorylation sites...
January 15, 2017: Analytica Chimica Acta
https://www.readbyqxmd.com/read/27915972/resistance-to-cell-death-and-its-modulation-in-cancer-stem-cells
#15
Ahmad R Safa
Accumulating evidence has demonstrated that human cancers arise from various tissues of origin that initiate from cancer stem cells (CSCs) or cancer-initiating cells. The extrinsic and intrinsic apoptotic pathways are dysregulated in CSCs, and these cells play crucial roles in tumor initiation, progression, cell death resistance, chemo- and radiotherapy resistance, and tumor recurrence. Understanding CSC-specific signaling proteins and pathways is necessary to identify specific therapeutic targets that may lead to the development of more efficient therapies selectively targeting CSCs...
2016: Critical Reviews in Oncogenesis
https://www.readbyqxmd.com/read/27914997/transcriptomic-profiles-of-striped-snakehead-fish-cells-ssn-1-infected-with-red-spotted-grouper-nervous-necrosis-virus-rgnnv-with-an-emphasis-on-apoptosis-pathway
#16
Wenjie Chen, Lizhu Yi, Shuangshuang Feng, Xiaodan Liu, Muhammad Asim, Yongcan Zhou, Jiangfeng Lan, Sanjie Jiang, Jiagang Tu, Li Lin
Nervous necrosis virus (NNV), the causative agent of viral nervous necrosis (VNN) disease, has caused mass mortality of cultured marine and freshwater fish worldwide, resulting in enormous economic losses in the aquaculture industry. However, the molecular mechanisms underlying the pathogenicity of NNV are still poorly understood. In this study, the transcriptomic profiles of striped snakehead fish (Channa striatus) cells (SSN-1) infected with red-spotted grouper NNV (RGNNV) were investigated using deep RNA sequencing technique...
November 30, 2016: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/27914529/agglutinin-isolated-from-arisema-heterophyllum-blume-induces-apoptosis-and-autophagy-in-a549-cells-through-inhibiting-pi3k-akt-pathway-and-inducing-er-stress
#17
Li-Xing Feng, Peng Sun, Tian Mi, Miao Liu, Wang Liu, Si Yao, Yi-Min Cao, Xiao-Lu Yu, Wan-Ying Wu, Bao-Hong Jiang, Min Yang, De-An Guo, Xuan Liu
Arisaema heterophyllum Blume is one of the three medicinal plants known as traditional Chinese medicine Rhizoma Arisaematis (RA). RA has been popularly used to treat patients with convulsions, inflammation, and cancer for a long time. However, the underlying mechanisms for RA effects are still unclear. The present study was designed to determine the cytotoxicity of agglutinin isolated from Arisema heterophyllum Blume (AHA) and explore the possible mechanisms in human non-small-cell lung cancer A549 cells. AHA with purity up to 95% was isolated and purified from Arisaema heterophyllum Blume using hydrophobic interaction chromatography...
November 2016: Chinese Journal of Natural Medicines
https://www.readbyqxmd.com/read/27913571/snord126-promotes-hcc-and-crc-cell-growth-by-activating-the-pi3k-akt-pathway-through-fgfr2
#18
Xianlong Fang, Dongmei Yang, Hongping Luo, Shuai Wu, Wenjie Dong, Jing Xiao, Sujing Yuan, Aimin Ni, Kang-Jian Zhang, Xin-Yuan Liu, Liang Chu
Small nucleolar RNA (snoRNA) dysfunctions have been associated with cancer development. SNORD126 is an orphan C/D box snoRNA that is encoded within introns 5-6 of its host gene, cyclin B1-interacting protein 1 (CCNB1IP1) The cancer-associated molecular mechanisms triggered by SNORD126 are not fully understood. Here, we demonstrate that SNORD126 is highly expressed in hepatocellular carcinoma (HCC) and colorectal cancer (CRC) patient samples. SNORD126 increased Huh-7 and SW480 cell growth and tumorigenicity in nude mice...
December 2, 2016: Journal of Molecular Cell Biology
https://www.readbyqxmd.com/read/27913532/t-cell-acute-lymphoblastic-leukemia
#19
Elizabeth A Raetz, David T Teachey
T-cell acute lymphoblastic leukemia (T-ALL) is biologically distinct from its B lymphoblastic (B-ALL) counterpart and shows different kinetic patterns of disease response. Although very similar regimens are used to treat T-ALL and B-ALL, distinctions in response to different elements of therapy have been observed. Similar to B-ALL, the key prognostic determinant in T-ALL is minimal residual disease (MRD) response. Unlike B-ALL, other factors including age, white blood cell count at diagnosis, and genetics of the ALL blasts are not independently prognostic when MRD response is included...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27912873/pomolic-acid-suppresses-hif1%C3%AE-vegf-mediated-angiogenesis-by-targeting-p38-mapk-and-mtor-signaling-cascades
#20
Ji-Hyun Park, Jaewoo Yoon, Byoungduck Park
BACKGROUND: Pomolic acid (PA), an active triterpenoid from Euscaphis japonica, inhibits the proliferation of a variety of cancer cells, but the molecular mechanisms of the anti-angiogenic potential of PA have not been fully elucidated in breast cancer cells. HYPOTHESIS/PURPOSE: We investigated the molecular mechanisms underlying the anti-angiogenic effect of PA in epidermal growth factor (EGF)-responsive human breast cancer cells, MCF-7 and MDA-MB-231, and human umbilical vascular endothelial cells (HUVEC)...
December 15, 2016: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
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