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Terry G Unterman
FoxO proteins are ancient targets of insulin action and play an important role in mediating effects of insulin on gene expression and metabolism. Regulation of FoxO function in the liver is critical for the ability of insulin to maintain glucose homeostasis and suppress hepatic glucose production (HGP), and dysregulation of FoxO function is thought to contribute to the pathogenesis of diabetes mellitus. Signaling by the insulin/PI3 kinase/Akt pathway suppresses FoxO function, and FoxO proteins also are regulated by counterregulatory factors and sirtuin deacetylases which increase their activity...
2018: Current Topics in Developmental Biology
Naresh Varma Seelam, Srinu Bodige, Parameshwar Ravula, Kali Charan Gulipalli, Srinivas Endoori, J N Narendra Sharath Chandra, Purna Koteswara Rao Cherukumalli, G R Vanaja
Phosphatidylinositol-3-kinase α (PI3Kα) is a ubiquitous intracellular enzyme, mainly involved in intracellular signaling pathways, promotes cellular growth, proliferation, and differentiation. Therefore, inhibition of PI3K can be a hotspot in molecular targeted therapy for the treatment of cancer. The present research work involves molecular docking studies performed to screen derivatives of urea and thiourea bearing thieno [3,2-d]-pyrimidines against the active site of PI3K enzyme using MOE.2008.10. The designed structures (6a-f) and (7a-j) were synthesized by the facile synthetic methods and evaluated for their anticancer activity against HT-29 and MCF-7 cell lines and inhibitory activity against PI3Kα enzyme...
February 9, 2018: Anti-cancer Agents in Medicinal Chemistry
H Richard Alexander, Claire Yue Li, Timothy J Kennedy
PURPOSE: Diffuse malignant peritoneal mesothelioma (MPM) is a rare and ultimately fatal cancer that was first described just over a century ago. It is a diffuse malignancy arising from the mesothelial lining of the peritoneum; morbidity and mortality from MPM is due to its propensity to progress locoregionally within the abdominal cavity. METHODS: The purpose of this article is to review the current state-of-the-science related to the diagnosis, staging, and treatment of MPM...
February 8, 2018: Annals of Surgical Oncology
Jian Ma, Smita Matkar, Xin He, Xianxin Hua
FOXO proteins are a sub-group of a superfamily of forkhead box (FOX)-containing transcription factors (TFs). FOXOs play an important role in regulating a plethora of biological activities ranging from development, cell signaling, and tumorigenesis to cell metabolism. Here we mainly focus on reviewing the role of FOXOs in regulating tumor and metabolism. Moreover, how crosstalk among various pathways influences the function of FOXOs will be reviewed. Further, the paradoxical role for FOXOs in controlling the fate of cancer and especially resistance/sensitivity of cancer to the class of drugs that target PI3 K/AKT will also be reviewed...
February 1, 2018: Seminars in Cancer Biology
Miriam Martini, Maria Chiara De Santis, Emilio Hirsch
Mitosis is a complex process controlling proper distribution of chromosomes and preventing genomic instability, a typical hallmark of cancer. We recently reported that that a class II isoform of Phosphoinositide 3-kinase (PI3K), PI3K-C2α, is involved in the organization of the mitotic spindle. Our study demonstrate that, differently to all other PI3K isoforms, PI3K-C2α shows an unexpected tumor suppressor function independent of its catalytic activity.
2018: Molecular & Cellular Oncology
Chun-Yu Li, Qi Wang, Shen Shen, Xiao-Lu Wei, Guo-Xia Li
Epithelial-mesenchymal transition (EMT) has been reported to play pivotal roles in tumor invasion and metastasis. Inhibition of EMT may exert beneficial effects in regulating metastasis. Oridonin (ORI), an active diterpenoid compound isolated from Rabdosia rubescens, was found to be a potent anti-metastatic agent. However, the possible involvement of ORI in the EMT in malignant melanoma is unclear. The present study found that ORI inhibited cell migration, invasion, and adhesion in A375 and B16-F10 melanoma cells...
January 2018: Oncology Letters
Philip Earwaker, Caroline Anderson, Frances Willenbrock, Adrian L Harris, Andrew S Protheroe, Valentine M Macaulay
The outlook for patients with advanced renal cell cancer (RCC) has been improved by targeted agents including inhibitors of the PI3 kinase (PI3K)-AKT-mTOR axis, although treatment resistance is a major problem. Here, we aimed to understand how RCC cells acquire resistance to PI3K-mTOR inhibition. We used the RCC4 cell line to generate a model of in vitro resistance by continuous culture in PI3K-mTOR kinase inhibitor NVP-BEZ235 (BEZ235, Dactolisib). Resistant cells were cross-resistant to mTOR inhibitor AZD2014...
2018: PloS One
Huijuan Liu, Qin Tian, Xiaoyu Ai, Yuan Qin, Zhanhong Cui, Meng Li, Jiahuan Yang, Denghui Zhai, Yanrong Liu, Shuang Chen, Jing Meng, Tao Sun, Honggang Zhou, Cheng Yang
Dihydroartemisinin (DHA) is the first generation of naturally occurring artemisinin derivatives with antimalarial activity. Recent research showed that this drug also features immunosuppressive and anti-inflammatory properties. Autoimmune thyroiditis (AIT) is a common organ-specific autoimmune disease with no available effective drug treatment. In this study, we investigated effects of DHA on AIT in vitro and in vivo. Results showed that DHA can visibly reduce antithyroglobulin antibody and thyroid peroxidase antibody levels and regulate T helper cells (Th) 1/Th2 imbalance of experimental AIT mice...
December 29, 2017: Oncotarget
Lili Zhang, Xiaoyan Wang, Yan Wu, Xiangru Lu, Peter Chidiac, Guoping Wang, Qingping Feng
Offspring of diabetic mothers are at risk of cardiovascular diseases in adulthood. However, the underlying molecular mechanisms are not clear. We hypothesize that prenatal exposure to maternal diabetes up-regulates myocardial NOX2 expression and enhances ischaemia/reperfusion (I/R) injury in the adult offspring. Maternal diabetes was induced in C57BL/6 mice by streptozotocin. Glucose-tolerant adult offspring of diabetic mothers and normal controls were subjected to myocardial I/R injury. Vascular endothelial growth factor (VEGF) expression, ROS generation, myocardial apoptosis and infarct size were assessed...
January 29, 2018: Journal of Cellular and Molecular Medicine
Hazel Quek, Yi Chieh Lim, Martin F Lavin, Tara L Roberts
The phosphoinositide-3-kinase like kinases are a family of very large protein kinases. These PI3-kinase like kinase (PIKK) proteins have well-established roles in detection and repair of damage to the genome, regulation of the transcriptome and cellular metabolism. Recently there has emerged, evidence for links between these proteins and inflammation. While some of these links come from an increased understanding of the impacts of damage to the cell on inflammatory responses, others suggest that PIKK proteins also have direct roles in regulation of immune responses...
January 2018: Immunology and Cell Biology
Takayuki Yamamoto, Tomohisa Okada, Yasutaka Fushimi, Akira Yamamoto, Koji Fujimoto, Sachi Okuchi, Hikaru Fukutomi, Jun C Takahashi, Takeshi Funaki, Susumu Miyamoto, Aurélien F Stalder, Yutaka Natsuaki, Peter Speier, Kaori Togashi
Compressed sensing (CS) reconstructions of under-sampled measurements generate missing data based on assumptions of image sparsity. Non-contrast time-of-flight MR angiography (TOF-MRA) is a good candidate for CS based acceleration, as MRA images feature bright trees of sparse vessels over a well-suppressed anatomical background signal. A short scan time derived from CS is beneficial for patients of moyamoya disease (MMD) because of the frequency of MR scans. The purpose of this study was to investigate the reliability of TOF-MRA with CS in the evaluation of MMD...
2018: PloS One
Lauren Geary, Carole LaBonne
Early vertebrate embryos possess cells with the potential to generate all embryonic cell types. While this pluripotency is progressively lost as cells become lineage restricted, Neural Crest cells retain broad developmental potential. Here, we provide novel insights into signals essential for both pluripotency and neural crest formation in Xenopus. We show that FGF signaling controls a subset of genes expressed by pluripotent blastula cells, and find a striking switch in the signaling cascades activated by FGF signaling as cells lose pluripotency and commence lineage restriction...
January 19, 2018: ELife
Emmanuel S Antonarakis
The notion that androgens and androgen receptor (AR) signaling are the hallmarks of prostate cancer oncogenesis and disease progression is generally well accepted. What is more poorly understood is the role of AR signaling in other human malignancies. This special issue of Cancers initially reviews the role of AR in advanced prostate cancer, and then explores the potential importance of AR signaling in other epithelial malignancies. The first few articles focus on the use of novel AR-targeting therapies in castration-resistant prostate cancer and the mechanisms of resistance to novel antiandrogens, and they also outline the interaction between AR and other cellular pathways, including PI3 kinase signaling, transcriptional regulation, angiogenesis, stromal factors, Wnt signaling, and epigenetic regulation in prostate cancer...
January 18, 2018: Cancers
Wei Wei, Yan Chen, Jie Xu, Yu Zhou, Xinping Bai, Ming Yang, Ju Zhu
Cutaneous squamous cell carcinoma (CSCC) is one of the most malignant tumors worldwide. We aimed to explore the molecular mechanism of this CSCC and screen feature genes that can function as the biomarker of CSCC and thus provide a theoretical basis for the pathogenesis research and development of medicine. The method of microarray data analysis was used in this study to explore the differentially expressed genes between tissues of normal specimens and tissues of patients with CSCC. Besides, functional enrichment analysis and signal pathway were performed on these genes to screen the feature genes that are closely associated with CSCC can function as the potential biomarkers of CSCC...
2018: Journal of Cancer
Mawiyah N Kimbrough-Allah, Ana C Millena, Shafiq A Khan
BACKGROUND: Transforming growth factor-β (TGF-β) acts as a tumor suppressor in normal epithelial cells but as a tumor promoter in advanced prostate cancer cells. PI3-kinase pathway mediates TGF-β effects on prostate cancer cell migration and invasion. PTEN inhibits PI3-kinase pathway and is frequently mutated in prostate cancers. We investigated possible role(s) of PTEN in TGF-β effects on proliferation and migration in prostate cancer cells. METHODS: Expression of PTEN mRNA and proteins were determined using RT-PCR and Western blotting in RWPE1 and DU145 cells...
January 16, 2018: Prostate
Beatrice Rubin, Jacopo Mansi, Halenya Monticelli, Loris Bertazza, Marco Redaelli, Francesca Sensi, Maira Zorzan, Carla Scaroni, Caterina Mian, Maurizio Iacobone, Decio Armanini, Cristina Bertolini, Susi Barollo, Marco Boscaro, Raffaele Pezzani
Oregano (Origanum vulgare L.) is a common aromatic plant used in Mediterranean and Asian Regions for treating respiratory diseases, painful menstruation, rheumatoid arthritis, etc. Recently its role as an anticancer plant has been suggested, although oregano has been never evaluated into adrenocortical tumour cell models. This study analysed for the first time the anticancer effects of a crude extract of wild mountain oregano (Origanum vulgare L.) in SW13 and H295R cell lines. The crude extract was characterised by GC/MS and the toxic effects of oregano were first analysed by brine shrimp lethality assay...
January 15, 2018: Natural Product Research
Tuba Sevimoglu, Beste Turanli, Ceyhun Bereketoglu, Kazim Yalcin Arga, Ayse Serap Karadag
Psoriasis is a complex autoimmune disease with multiple genes and proteins being involved in its pathogenesis. Despite the efforts performed to understand mechanisms of psoriasis pathogenesis and to identify diagnostic and prognostic targets, disease-specific and effective biomarkers were still not available. This study is compiled regarding clinical validation of computationally proposed biomarkers at gene and protein expression levels through qRT-PCR and ELISA techniques using skin biopsies and blood plasma...
January 9, 2018: Gene
Enas Hussein Ali, Fatemeh Sharifpanah, Maria Wartenberg, Heinrich Sauer
Silibinin, the bioactive compound of milk thistle (Silybum marianum), exerts tissue protective and regenerative effects that may include stem cell differentiation toward vascular cells. The purpose of the present study was to investigate whether silibinin stimulates blood vessel formation from mouse embryonic stem (ES) cells and to unravel the underlying signaling cascade. Vascular branching points were assessed by confocal laser scanning microscopy and computer-assisted image analysis of CD31-positive cell structures...
January 12, 2018: Planta Medica
Mohammed Loubidi, Jabrane Jouha, Zahira Tber, Mostafa Khouili, Franck Suzenet, Mohamed Akssira, Mümin Alper Erdogan, Fadime Aydın Köse, Taner Dagcı, Güliz Armagan, Luciano Saso, Gérald Guillaumet
Oxidative stress and apoptosis are both associated with various acute and chronic disorders. Thus, the aim of the present study is to synthesize imidazo[2,1-c][1,2,4]triazines derivatives and to evaluate their effects in H2O2-induced oxidative stress in human neuroblastoma cell line (SH-SY5Y cells). The effects of the compounds on cell viability were measured by MTT assay and the changes in stress and apoptosis-related proteins were investigated by PathScan® Stress and Apoptosis Signaling Antibody Array kit and Western Blot technique...
December 27, 2017: European Journal of Medicinal Chemistry
Sathiya Sekar, Changiz Taghibiglou
Studies showed that 50-80% of Parkinson's disease (PD) patients have been reported with abnormal glucose tolerance. Alterations in glucose and energy metabolism serve as the early molecular event in PD. Although evidences support that the insulin resistance plays a major role in motor and non-motor complications of PD, the underlying mechanism in the pathogenesis of PD is unclear. To address this issue, we investigated the alterations in major components of insulin signaling in nuclear fraction (NF) and whole tissue homogenate (TH) of substantia nigral (SN) region obtained from postmortem PD brain and their age-matched controls...
December 26, 2017: Neuroscience Letters
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