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https://www.readbyqxmd.com/read/28231559/prostate-cancer-heterogeneity-discovering-novel-molecular-targets-for-therapy
#1
REVIEW
Chiara Ciccarese, Francesco Massari, Roberto Iacovelli, Michelangelo Fiorentino, Rodolfo Montironi, Vincenzo Di Nunno, Francesca Giunchi, Matteo Brunelli, Giampaolo Tortora
Prostate cancer (PCa) shows a broad spectrum of biological and clinical behavior, which represents the epiphenomenon of an extreme genetic heterogeneity. Recent genomic profiling studies have deeply improved the knowledge of the genomic landscape of localized and metastatic PCa. The AR and PI3K/Akt/mTOR signaling pathways are the two most frequently altered, representing therefore interestingly targets for therapy. Moreover, somatic or germline aberrations of DNA repair genes (DRGs) have been observed at high frequency, supporting the potential role of platinum derivatives and PARP inhibitors as effective therapeutic strategies...
February 11, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28231545/aqueous-extract-of-cortex-dictamni-protects-h9c2-cardiomyocytes-from-hypoxia-reoxygenation-induced-oxidative-stress-and-apoptosis-by-pi3k-akt-signaling-pathway
#2
Lin Li, Yunfeng Zhou, Yanlin Li, Lili Wang, Lan Sun, Lidong Zhou, Hiderori Arai, Yun Qi, Yang Xu
Ischemia-reperfusion injury is the major manifestation of ischemic heart disease, which facilitates cardiac arrhythmias, heart failure and death. Oxidative stress and apoptosis have been involved in the pathogenesis of myocardial ischemia-reperfusion injury. Modern pharmacological studies have indicated that the extracts and active compounds of Cortex Dictamni exhibit antioxidative and cardiovascular protective activities. This study was designed to investigate the protective effect of aqueous extract of Cortex Dictamni (CDAE) on regulating hypoxia/reoxygenation (H/R)-induced cardiomyocytes oxidative stress and apoptosis...
February 20, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28230926/association-between-high-expression-of-phosphorylated-akt-and-mammalian-target-of-rapamycin-and-improved-survival-in-salivary-gland-adenoid-cystic-carcinoma
#3
Dai-Qiao Ouyang, Li-Zhong Liang, Zun-Fu Ke, Guang-Sen Zheng, De-Sheng Weng, Wei-Fa Yang, Yu-Xiong Su, Gui-Qing Liao
BACKGROUND: Previous genomic studies revealed phosphotidylinositol-3-kinase (PI3K)/Akt pathway mutation in human salivary gland adenoid cystic carcinoma (ACC). No validation of its prognostic value has been reported. METHODS: P-Akt, pan-Akt, phosphorylated-mammalian target of rapamycin (p-mTOR), PI3K, and insulin-like growth factor-1 receptor beta (IGF-1Rβ) were detected on 120 salivary gland ACC/adjacent salivary gland pairs immunohistochemically and were correlated with clinicopathological data...
February 23, 2017: Head & Neck
https://www.readbyqxmd.com/read/28230361/10-gingerol-a-phytochemical-derivative-from-tongling-white-ginger-inhibits-cervical-cancer-insights-into-the-molecular-mechanism-and-inhibitory-targets
#4
Fang Zhang, Kiran Thakur, Fei Hu, Jian-Guo Zhang, Zhao-Jun Wei
With an aim to evaluate anti-cancerous activities of 10-gingerol (10-G) against Hela cells, it was purified and identified from Tongling White Ginger by HSCCC, UPLC-TOF-MS/MS and NMR analysis, respectively. 10-G inhibited the proliferation of HeLa cells at IC50 (29.19 μM) and IC80 (50.87 μM) with altered cell morphology, increased cytotoxicity and arrested cell cycle in G0/G1-phase. The most cell cycle related genes and proteins expression significantly decreased, followed by slight decrease in few and without affecting cyclin B1 and cyclin E1 (protein)...
February 23, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28230291/therapeutic-potentials-of-bdnf-trkb-in-breast-cancer-current-status-and-perspectives
#5
Amir Tajbakhsh, Amin Mokhtari-Zaer, Mehdi Rezaee, Fahimeh Afzaljavan, Mehdi Rivandi, Seyed Mahdi Hassanian, Gordon A Ferns, Alireza Pasdar, Amir Avan
Brain-derived neurotrophic factor (BDNF) is a potent neurotrophic factor that has been shown to stimulate breast cancer cell growth and metastasis via tyrosine kinase receptors TrkA, TrkB and the p75(NTR) death receptor. The aberrant activation of BDNF/TrkB pathways can modulate several signaling pathways, including Akt/PI3K, Jak/STAT, NF-kB, UPAR/UPA, Wnt/β-catenin and VEGF pathways as well as the ER receptor. Several microRNAs have been identified that are involved in the modulation of BDNF/TrkB pathways...
February 23, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28230287/therapeutic-potential-of-targeting-pi3k-akt-pathway-in-treatment-of-colorectal-cancer-rational-and-progress
#6
Afsane Bahrami, Majid Khazaei, Malihe Hasanzadeh, Soodabeh ShahidSales, Mona Joudi Mashhad, Marjaneh Farazestanian, Hamid Reza Sadeghnia, Majid Rezayi, Mina Maftouh, Seyed Mahdi Hassanian, Amir Avan
PI3K/AKT/mTOR signaling pathway is one of the key dysregulated pathways in different tumor types, including colorectal cancer (CRC). Activation of this pathway is shown to be related with cellular transformation, tumor progression, cell survival and drug resistance. There is growing body of data evaluating the value of PI3K/AKT/mTOR inhibitors in CRC (e.g., BEZ235, NVP-BEZ235, OSI-027, everolimus, MK-2206, KRX-0401, BYL719 and BKM120). This report summarizes the current knowledge about PI3K/AKT pathway and its cross talk with ERK/MAPK and mTOR pathways with particular emphasis on the value of targeting this pathway as a potential therapeutic target in treatment of colorectal cancer...
February 23, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28230206/mirna-21-mediates-the-antiangiogenic-activity-of-metformin-through-targeting-pten-and-smad7-expression-and-pi3k-akt-pathway
#7
Mao Luo, Xiaoyong Tan, Lin Mu, Yulin Luo, Rong Li, Xin Deng, Ni Chen, Meiping Ren, Yongjie Li, Liqun Wang, Jianbo Wu, Qin Wan
Metformin, an anti-diabetic drug commonly used for type 2 diabetes therapy, is associated with anti-angiogenic effects in conditions beyond diabetes. miR-21 has been reported to be involved in the process of angiogenesis. However, the precise regulatory mechanisms by which the metformin-induced endothelial suppression and its effects on miR-21-dependent pathways are still unclear. Bioinformatic analysis and identification of miR-21 and its targets and their effects on metformin-induced antiangiogenic activity were assessed using luciferase assays, quantitative real-time PCR, western blots, scratch assays, CCK-8 assays and tubule formation assays...
February 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28229364/molecular-subtyping-in-diffuse-large-b-cell-lymphoma-closer-to-an-approach-of-precision-therapy
#8
REVIEW
Reem Karmali, Leo I Gordon
It has become clear that there is immense biological heterogeneity in diffuse large B cell lymphoma (DLBCL). Developing technology has allowed better characterization of patient subsets at a molecular level, allowing for a link of phenotype and clinical outcomes to oncogenic mechanisms and biologic signatures. Cell of origin and double hit status are able to identify aggressive subsets, with molecular profiling allowing for a clearer understanding of biologic pathways that contribute to cellular resistance to conventional treatment in these subsets...
February 2017: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/28229220/overexpression-of-hepacam-inhibits-bladder-cancer-cell-proliferation-and-viability-through-the-akt-foxo-pathway
#9
Min Tang, Yan Zhao, Nanjing Liu, E Chen, Zhen Quan, Xiaohou Wu, Chunli Luo
PURPOSE: HepaCAM, an N-linked glycoprotein that encodes a member of the immunoglobulin superfamily, has been reported to be a tumor suppressor gene that mediates diverse cellular bio-functions. Recent studies have shown that the FoxO transcription factors play a pivotal role during cancer progression. Here, we explored the correlation between HepaCAM and the FoxO family via regulation of the PI3K/AKT pathway. METHODS: HepaCAM and FoxO3 expression were detected by immunohistochemistry staining...
February 22, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28228749/neuroprotective-role-of-the-pi3-kinase-akt-signaling-pathway-in-zebrafish
#10
Shuang Chen, Yunzhang Liu, Xiaozhi Rong, Yun Li, Jianfeng Zhou, Ling Lu
Neuronal survival and growth in the embryo is controlled partly by trophic factors. For most trophic factors (such as Insulin-like growth factor-1), the ability to regulate cell survival has been attributed to the phosphoinositide 3-kinase (PI3K)/Akt kinase cascade. This study presents data illustrating the role of PI3K/Akt in attainment of normal brain size during zebrafish embryogenesis. Blocking PI3K with inhibitor LY294002 caused a significant reduction in brain size (in addition to global growth retardation) during zebrafish embryogenesis...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28228706/the-pi3k-pathway-background-and-treatment-approaches
#11
REVIEW
Michael P Lux, Peter A Fasching, Michael G Schrauder, Alexander Hein, Sebastian M Jud, Claudia Rauh, Matthias W Beckmann
Two-thirds of all breast cancer patients with metastases have a hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative subtype. Endocrine therapy is the treatment of choice in these patients since in addition to its effectiveness it can also maintain the patients' quality of life over a longer term. However, 44-62% of postmenopausal patients with metastatic breast carcinoma have primary tamoxifen resistance. After 3-5 years, 30-40% of the patients receiving tamoxifen treatment develop secondary resistance...
December 2016: Breast Care
https://www.readbyqxmd.com/read/28228253/sirt6-suppresses-cancer-stem-like-capacity-in-tumors-with-pi3k-activation-independently-of-its-deacetylase-activity
#12
Rafael M Ioris, Mirco Galié, Giorgio Ramadori, Jason G Anderson, Anne Charollais, Georgia Konstantinidou, Xavier Brenachot, Ebru Aras, Algera Goga, Nicholas Ceglia, Carlos Sebastián, Denis Martinvalet, Raul Mostoslavsky, Pierre Baldi, Roberto Coppari
Cancer stem cells (CSCs) have high tumorigenic capacity. Here, we show that stem-like traits of specific human cancer cells are reduced by overexpression of the histone deacetylase sirtuin 6 (SIRT6). SIRT6-sensitive cancer cells bear mutations that activate phosphatidylinositol-3-kinase (PI3K) signaling, and overexpression of SIRT6 reduces growth, progression, and grade of breast cancer in a mouse model with PI3K activation. Tumor metabolomic and transcriptomic analyses reveal that SIRT6 overexpression dampens PI3K signaling and stem-like characteristics and causes metabolic rearrangements in this cancer model...
February 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28225806/capsaicin-reduces-alzheimer-associated-tau-changes-in-the-hippocampus-of-type-2-diabetes-rats
#13
Weijie Xu, Juanhong Liu, Delin Ma, Gang Yuan, Yan Lu, Yan Yang
Type 2 diabetes (T2D) is a high-risk factor for Alzheimer's disease (AD) due to impaired insulin signaling pathway in brain. Capsaicin is a specific transient receptor potential vanilloid 1 (TRPV1) agonist which was proved to ameliorate insulin resistance. In this study, we investigated whether dietary capsaicin could reduce the risk of AD in T2D. T2D rats were fed with capsaicin-containing high fat (HF) diet for 10 consecutive days (T2D+CAP). Pair-fed T2D rats (T2D+PF) fed with the HF-diet of average dose of T2D+CAP group were included to control for the effects of reduced food intake and body weight...
2017: PloS One
https://www.readbyqxmd.com/read/28225063/targeted-inhibition-of-focal-adhesion-kinase-attenuates-cardiac-fibrosis-and-preserves-heart-function-in-adverse-cardiac-remodeling
#14
Jie Zhang, Guangpu Fan, Hui Zhao, Zhiwei Wang, Fei Li, Peide Zhang, Jing Zhang, Xu Wang, Wei Wang
Cardiac fibrosis in post-myocardial infarction (MI), seen in both infarcted and non-infarcted myocardium, is beneficial to the recovery of heart function. But progressively pathological fibrosis impairs ventricular function and leads to poor prognosis. FAK has recently received attention as a potential mediator of fibrosis, our previous study reported that pharmacological inhibition of FAK can attenuate cardiac fibrosis in post MI models. However, the long-term effects on cardiac function and adverse cardiac remodelling were not clearly investigated...
February 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28225015/identification-of-protein-biomarkers-and-signaling-pathways-associated-with-prostate-cancer-radioresistance-using-label-free-lc-ms-ms-proteomic-approach
#15
Lei Chang, Jie Ni, Julia Beretov, Valerie C Wasinger, Jingli Hao, Joseph Bucci, David Malouf, David Gillatt, Peter H Graham, Yong Li
Identifying biomarkers and signaling pathways are important for the management of prostate cancer (CaP) radioresistance. In this study, we identified differential proteins and signaling pathways from parental CaP cell lines and CaP radioresistant (RR) sublines using a label-free LC-MS/MS proteomics approach. A total of 309 signaling pathway proteins were identified to be significantly altered between CaP and CaP-RR cells (p ≤ 0.05, fold differences >1.5, ≥80% power). Among these proteins, nineteen are common among three paired CaP cell lines and associated with metastasis, progression and radioresistance...
February 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28224609/mir-181-elevates-akt-signaling-by-co-targeting-phlpp2-and-inpp4b-phosphatases-in-luminal-breast-cancer
#16
Michaela Strotbek, Simone Schmid, Ismael Sànchez-Gonzàlez, Melanie Boerries, Hauke Busch, Monilola A Olayioye
The PI3K-Akt pathway is one of the most commonly dysregulated cancer-associated signaling pathways. Here we report an oncogenic function for the miR-181 family in luminal breast cancer cells that involves Akt hyperactivation. We show that miR-181a and miR-181d post-transcriptionally suppress the expression of PHLPP2 and INPP4B phosphatases, resulting in elevated growth factor-induced Akt phosphorylation. Ectopic expression of miR-181a and miR-181d promoted S-phase entry and cell proliferation, which was reversed by pharmacological Akt inhibition...
February 22, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28223935/morus-alba-leaf-lectin-mll-sensitizes-mcf-7-cells-to-anoikis-by-inhibiting-fibronectin-mediated-integrin-fak-signaling-through-ras-and-activation-of-p-38-mapk
#17
Jayaram Saranya, Ganesan Shilpa, Kozhiparambil G Raghu, Sulochana Priya
Lectins are a unique class of carbohydrate binding proteins/glycoproteins, and many of them possess anticancer properties. They can induce cell cycle arrest and apoptosis, inhibit protein synthesis, telomerase activity and angiogenesis in cancer cells. In the present study, we have demonstrated the effect of Morus alba leaf lectin (MLL) on anoikis induction in MCF-7 cells. Anoikis induction in cancer cells has a significant role in preventing early stage metastasis. MLL treatment in monolayers of MCF-7 cells caused significant detachment of cells in a time and concentration dependent manner...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28223777/phloretin-exerts-hypoglycemic-effect-in-streptozotocin-induced-diabetic-rats-and-improves-insulin-resistance-in-vitro
#18
Xin Shen, Nan Zhou, Le Mi, Zishuo Hu, Libin Wang, Xueying Liu, Shengyong Zhang
The present study investigated the possible antiobesity and hypoglycemic effects of phloretin (Ph). In an attempt to discover the hypoglycemic effect and potential mechanism of Ph, we used the streptozotocin-induced diabetic rats and (L6) myotubes. Daily oral treatment with Ph for 4 weeks significantly (P<0.05) reduced postprandial blood glucose and improved islet injury and lipid metabolism. Glucose consumption and glucose tolerance were improved by Ph via GOD-POD method. Western blot results revealed that the expression of Akt, PI3K, IRS-1, and GLUT4 were upregulated in skeletal muscle of type 2 diabetes (T2D) rats and in L6 myotubes by Ph...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28223727/remote-ischemic-perconditioning-prevents-liver-transplantation-induced-ischemia-reperfusion-injury-in-rats-role-of-ros-rns-and-enos
#19
Ning He, Jun-Jun Jia, Jian-Hui Li, Yan-Fei Zhou, Bing-Yi Lin, Yi-Fan Peng, Jun-Jie Chen, Tian-Chi Chen, Rong-Liang Tong, Li Jiang, Hai-Yang Xie, Lin Zhou, Shu-Sen Zheng
AIM: To investigate the underlying mechanisms of the protective role of remote ischemic perconditioning (RIPerC) in rat liver transplantation. METHODS: Sprague-Dawley rats were subjected to sham, orthotopic liver transplantation (OLT), ischemic postconditioning (IPostC) or RIPerC. After 3 h reperfusion, blood samples were taken for measurement of alanine aminotransferase, aspartate aminotransferase, creatinine (Cr) and creatinine kinase-myocardial band (CK-MB). The liver lobes were harvested for the following measurements: reactive oxygen species (ROS), H2O2, mitochondrial membrane potential (ΔΨm) and total nitric oxide (NO)...
February 7, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28223693/single-cd28-stimulation-induces-stable-and-polyclonal-expansion-of-human-regulatory-t-cells
#20
Xuehui He, Ruben L Smeets, Esther van Rijssen, Annemieke M H Boots, Irma Joosten, Hans J P M Koenen
CD4+FOXP3+ Treg are essential for immune tolerance. Phase-1 clinical trials of Treg-therapy to treat graft-versus-host-disease reported safety and potential therapeutic efficacy. Treg-based trials have started in organ-transplant patients. However, efficient ex vivo expansion of a stable Treg population remains a challenge and exploring novel ways for Treg expansion is a pre-requisite for successful immunotherapy. Based on the recent finding that CD28-signaling is crucial for survival and proliferation of mouse Treg, we studied single-CD28 stimulation of human Treg, without T cell receptor stimulation...
February 22, 2017: Scientific Reports
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