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https://www.readbyqxmd.com/read/28350865/multi-drug-loaded-micelles-delivering-chemotherapy-and-targeted-therapies-directed-against-hsp90-and-the-pi3k-akt-mtor-pathway-in-prostate-cancer
#1
Bao Le, Ginny L Powers, Yu Tong Tam, Nicholas Schumacher, Rita L Malinowski, Laura Steinke, Glen Kwon, Paul C Marker
BACKGROUND: Advanced prostate cancers that are resistant to all current therapies create a need for new therapeutic strategies. One recent innovative approach to cancer therapy is the simultaneous use of multiple FDA-approved drugs to target multiple pathways. A challenge for this approach is caused by the different solubility requirements of each individual drug, resulting in the need for a drug vehicle that is non-toxic and capable of carrying multiple water-insoluble antitumor drugs...
2017: PloS One
https://www.readbyqxmd.com/read/28345313/acute-hyperglycemia-associated-with-anti-cancer-medication
#2
REVIEW
Yul Hwangbo, Eun Kyung Lee
Hyperglycemia during chemotherapy occurs in approximately 10% to 30% of patients. Glucocorticoids and L-asparaginase are well known to cause acute hyperglycemia during chemotherapy. Long-term hyperglycemia is also frequently observed, especially in patients with hematologic malignancies treated with L-asparaginase-based regimens and total body irradiation. Glucocorticoid-induced hyperglycemia often develops because of increased insulin resistance, diminished insulin secretion, and exaggerated hepatic glucose output...
March 2017: Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28345271/immunosuppression-with-mtor-inhibitors-prevents-the-development-of-donor-specific-antibodies-after-liver-transplant
#3
Katharina Willuweit, Andreas Heinold, Jassin Rashidi-Alavijeh, Falko M Heinemann, Peter A Horn, Andreas Paul, Guido Gerken, Kerstin Herzer
BACKGROUND: Donor-specific antibodies (DSAs) are an important cause of complications after solid-organ transplant. Risk factors and, thus, strategies for preventing DSA development are not well defined. METHODS: The DSA status of 400 patients who underwent LT at the outpatient clinic of the University Hospital Essen, was determined. Human leukocyte antigen (HLA) antibodies were detected by single-antigen bead technology. The strength of DSAs was reported as mean fluorescence intensity (MFI)...
March 26, 2017: Clinical Transplantation
https://www.readbyqxmd.com/read/28344663/everolimus-treatment-for-neuroendocrine-tumors-latest-results-and-clinical-potential
#4
REVIEW
Sara Pusceddu, Elena Verzoni, Natialie Prinzi, Alessia Mennitto, Daniela Femia, Paolo Grassi, Laura Concas, Claudio Vernieri, Giuseppe Lo Russo, Giuseppe Procopio
Neuroendocrine tumors (NETs) are a heterogeneous class of diseases characterized by challenging management. Preclinical evidence shows that the PI3K/AKT/mTOR signaling pathway plays a central role in the pathogenesis and progression of NETs. Everolimus is a direct inhibitor of this pathway, and therefore this molecule appears to be a well-grounded strategy for the treatment of NETs, capable of changing clinical practice. The efficacy and safety of everolimus was demonstrated in the RADIANT trials. In this work, we comment on the results of the RADIANT trials, and other recent key evidence from fully published clinical trials on everolimus, and we discuss the current role of everolimus in the treatment of NETs...
March 2017: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/28341244/imperatorin-suppresses-proliferation-and-angiogenesis-of-human-colon-cancer-cell-by-targeting-hif-1%C3%AE-via-the-mtor-p70s6k-4e-bp1-and-mapk-pathways
#5
Chunliu Mi, Juan Ma, Ke Si Wang, Hong Xiang Zuo, Zhe Wang, Ming Yue Li, Lian Xun Piao, Guang Hua Xu, Xuezheng Li, Zhe Shan Quan, Xuejun Jin
ETHNOPHARMACOLOGICAL RELEVANCE: Angelica dahurica is a commonly used traditional Chinese medicine to treat migraine headache, toothache and cancer. Imperatorin is an active natural furocoumarin component originating from Angelica dahurica and has been shown to exhibit multiple bioeffector functions, including anti-cancer activity. However, the mechanism by which imperatorin inhibits tumor growth is not fully understood. AIM OF THE STUDY: The aim of this study was to investigate the effectiveness of imperatorin as a treatment of cancer and to identify the underlying mechanisms of its anticancer activity...
March 21, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28339096/pathogenesis-and-management-of-antiphospholipid-syndrome
#6
REVIEW
Deepa R J Arachchillage, Mike Laffan
Antiphospholipid antibodies are a heterogeneous group of autoantibodies that have clear associations with thrombosis and pregnancy morbidity, and which together constitute the 'antiphospholipid syndrome' (APS). However, the pathophysiology of these complications is not well understood and their heterogeneity suggests that more than one pathogenic process may be involved. Diagnosis remains a combination of laboratory analysis and clinical observation but there have been significant advances in identifying specific pathogenic features, such as domain I-specific anti-β2-glycoprotein-I antibodies...
March 24, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28339020/metformin-inhibits-endothelial-progenitor-cell-migration-by-decreasing-matrix-metalloproteinases-mmp-2-and-mmp-9-via-the-ampk-mtor-autophagy-pathway
#7
Wen-Dong Li, Neng-Ping Li, Dan-Dan Song, Jian-Jie Rong, Ai-Min Qian, Xiao-Qiang Li
The aim of the present study was to investigate the effect of metformin on endothelial progenitor cell (EPC) migration and to explore the possible mechanisms. EPCs were treated with metformin, and the migration of EPCs was evaluated by wound healing and Matrigel invasion assays. We also examined the expression levels of of MMP-2 and MMP-9 in EPCs with or without metformin treatment via RT-PCR and western blot analysis, and activities of MMP-2 and MMP-9 in EPCs under different conditions was examined by zymography...
March 21, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28337019/apigenin-induced-lysosomal-degradation-of-%C3%AE-catenin-in-wnt-%C3%AE-catenin-signaling
#8
Chung-Ming Lin, Hsin-Han Chen, Chun-An Lin, Hui-Chung Wu, Jim Jinn-Chyuan Sheu, Hui-Jye Chen
The bioflavonoid apigenin has been shown to possess cancer-preventive and anti-cancer activities. In a drug screening, we found that apigenin can inhibit Wnt/β-catenin signaling, a pathway that participates in pivotal biological functions, which dis-regulation results in various human diseases including cancers. However, the underlying mechanism of apigenin in this pathway and its link to anti-cancer activities remain largely unknown. Here we showed that apigenin reduced the amount of total, cytoplasmic, and nuclear β-catenin, leading to the suppression in the β-catenin/TCF-mediated transcriptional activity, the expression of Wnt target genes, and cell proliferation of Wnt-stimulated P19 cells and Wnt-driven colorectal cancer cells...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28335215/rapamycin-loaded-solid-lipid-nanoparticles-as-a-new-tool-to-deliver-mtor-inhibitors-formulation-and-in-vitro-characterization
#9
Alice Polchi, Alessandro Magini, Jarosław Mazuryk, Brunella Tancini, Jacek Gapiński, Adam Patkowski, Stefano Giovagnoli, Carla Emiliani
Recently, the use of mammalian target of rapamycin (mTOR) inhibitors, in particular rapamycin (Rp), has been suggested to improve the treatment of neurodegenerative diseases. However, as Rp is a strong immunosuppressant, specific delivery to the brain has been postulated to avoid systemic exposure. In this work, we fabricated new Rp loaded solid lipid nanoparticles (Rp-SLN) stabilized with polysorbate 80 (PS80), comparing two different methods and lipids. The formulations were characterized by differential scanning calorimetry (DSC), nuclear magnetic resonance (NMR), wide angle X-ray scattering (WAXS), cryo-transmission electron microscopy (cryo-TEM), dynamic light scattering (DLS) and particle tracking...
May 9, 2016: Nanomaterials
https://www.readbyqxmd.com/read/28334504/redd1-deficiency-impairs-autophagy-and-mitochondrial-biogenesis-in-articular-cartilage-and-increases-the-severity-of-experimental-osteoarthritis
#10
Oscar Alvarez-Garcia, Tokio Matsuzaki, Merissa Olmer, Lars Plate, Jeffery W Kelly, Martin K Lotz
Objective REDD1 is an endogenous inhibitor of mTOR that regulates cellular stress responses. REDD1 expression is decreased in aged and osteoarthritis (OA) cartilage and it regulates mTOR signaling and autophagy in articular chondrocytes in vitro. The present study investigated the effects of REDD1 deletion in vivo using a mouse model of experimental OA. Methods Severity of OA was histologically assessed in 4-month-old wild-type and in Redd1(-/-) mice subjected to surgical destabilization of the medial meniscus (DMM)...
March 23, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28334043/cc-223-blocks-mtorc1-c2-activation-and-inhibits-human-hepatocellular-carcinoma-cells-in-vitro-and-in-vivo
#11
Zichen Xie, Jiqin Wang, Mei Liu, Deshan Chen, Chao Qiu, Keyu Sun
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related human mortalities. Over-activation of mammalian target of rapamycin (mTOR) is important for HCC tumorigenesis and progression. The current study assessed the potential anti-HCC activity by a novel mTOR kinase inhibitor, CC-223. We demonstrate that CC-223, at nM concentrations, induced profound cytotoxic and anti-proliferative activities against established HCC cell lines (HepG2, KYN-2 and Huh-7) and primary human HCC cells. Meanwhile, CC-223 activated caspase-3/-9 and apoptosis in the above HCC cells...
2017: PloS One
https://www.readbyqxmd.com/read/28333860/cardiovascular-parameters-to-2-years-after-kidney-transplantation-following-early-switch-to-everolimus-without-calcineurin-inhibitor-therapy-an-analysis-of-the-randomized-elevate-study
#12
Hallvard Holdaas, Johan W de Fijter, Josep M Cruzado, Pablo Massari, Björn Nashan, John Kanellis, Oliver Witzke, Alex Gutierrez-Dalmau, Aydin Turkmen, Zailong Wang, Patricia Lopez, Peter Bernhardt, Jossy Kochuparampil, Markus van der Giet, Klaus Murbraech
BACKGROUND: Mammalian target of rapamycin (mTOR) inhibitors may confer cardioprotective advantages but clinical data are limited. METHODS: In the open-label ELEVATE trial, kidney transplant patients were randomized at 10-14 weeks posttransplant to convert from calcineurin inhibitor (CNI) to everolimus or remain on standard CNI therapy. Prespecified endpoints included left ventricular mass index (LVMi) and, in a subpopulation of patients, arterial stiffness as measured by pulse wave velocity (PWV)...
March 22, 2017: Transplantation
https://www.readbyqxmd.com/read/28332630/pml-nuclear-bodies-contribute-to-the-basal-expression-of-the-mtor-inhibitor-ddit4
#13
Jayme Salsman, Alex Stathakis, Ellen Parker, Dudley Chung, Livia E Anthes, Kara L Koskowich, Sara Lahsaee, Daniel Gaston, Kimberly R Kukurba, Kevin S Smith, Ian C Chute, Daniel Léger, Laura D Frost, Stephen B Montgomery, Stephen M Lewis, Christopher Eskiw, Graham Dellaire
The promyelocytic leukemia (PML) protein is an essential component of PML nuclear bodies (PML NBs) frequently lost in cancer. PML NBs coordinate chromosomal regions via modification of nuclear proteins that in turn may regulate genes in the vicinity of these bodies. However, few PML NB-associated genes have been identified. PML and PML NBs can also regulate mTOR and cell fate decisions in response to cellular stresses. We now demonstrate that PML depletion in U2OS cells or TERT-immortalized normal human diploid fibroblasts results in decreased expression of the mTOR inhibitor DDIT4 (REDD1)...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28330814/ala-pdt-suppressing-the-cell-growth-and-reducing-the-lipogenesis-in-human-sz95-sebocytes-by-mtor-signaling-pathway-in-vitro
#14
Jiang Tuo, Qianqian Wang, Ye Liu, Ying Ma, Li Ma, Jiayi Ying, Chengfeng Zhang, Leihong Xiang
BACKGROUND: 5-Aminolevulinic acid mediated -photodynamic therapy (ALA-PDT) is known to be effective in treating acne vulgaris and other sebaceous gland-related diseases. However, thetherapeutic mechanisms of ALA-PDT still remain undetermined. In this study, we aimed to investigate theeffects and mechanisms of ALA-PDTon the cell growth and lipogenesis of human SZ95 sebocytes. MATERIAL AND METHODS: Human SZ95 sebocytes were treated with different concentration of ALA-PDT...
March 19, 2017: Photodiagnosis and Photodynamic Therapy
https://www.readbyqxmd.com/read/28330462/prospective-phase-ii-trial-of-everolimus-in-pik3ca-amplification-mutation-and-or-pten-loss-patients-with-advanced-solid-tumors-refractory-to-standard-therapy
#15
Seung Tae Kim, Jeeyun Lee, Se Hoon Park, Joon Oh Park, Young Suk Park, Won Ki Kang, Ho Yeong Lim
BACKGROUND: We designed a single-arm, open-label phase II trial of everolimus in PIK3CA amplification/mutation and/or PTEN loss patients with advanced solid tumors refractory to standard therapy (#NCT02449538). METHODS: Everolimus was administered orally at a daily dose of 10 mg continuously (28-day cycles). Treatment was continued until progression of the disease or intolerable toxicity was observed. Based on Simon's two-stage optimal design, 10 patients were treated with everolimus during the first stage...
March 23, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28327903/successful-mtor-inhibitor-therapy-for-a-metastastic-neuroendocrine-tumour-in-a-patient-with-a-germline-tsc2-mutation
#16
J Schrader, F O Henes, D Perez, S Burdak-Rothkamm, A Stein, J R Izbicki, A W Lohse
No abstract text is available yet for this article.
March 6, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28327001/autophagy-promotes-the-repair-of-radiation-induced-dna-damage-in-bone-marrow-hematopoietic-cells-via-enhanced-stat3-signaling
#17
Fei Xu, Xin Li, Lili Yan, Na Yuan, Yixuan Fang, Yan Cao, Li Xu, Xiaoying Zhang, Lan Xu, Chaorong Ge, Ni An, Gaoyue Jiang, Jialing Xie, Han Zhang, Jiayi Jiang, Xiaotian Li, Lei Yao, Suping Zhang, Daohong Zhou, Jianrong Wang
Autophagy protects hematopoietic cells from radiation damage in part by promoting DNA damage repair. However, the molecular mechanisms by which autophagy regulates DNA damage repair remain largely elusive. Here, we report that this radioprotective effect of autophagy depends on STAT3 signaling in murine bone marrow mononuclear cells (BM-MNCs). Specifically, we found that STAT3 activation and nuclear translocation in BM-MNCs were increased by activation of autophagy with an mTOR inhibitor and decreased by knockout of the autophagy gene Atg7...
March 2017: Radiation Research
https://www.readbyqxmd.com/read/28326537/gax-suppresses-chemerin-cmklr1-induced-preadipocyte-biofunctions-through-the-inhibition-of-akt-mtor-and-erk-signaling-pathways
#18
Yunqi Jiang, Ping Liu, Wenlin Jiao, Juan Meng, Jinbo Feng
Adipose tissue is closely associated with angiogenesis and vascular remodeling. Chemerin is involved in inflammatory reaction and vascular dysfunction. However, the mechanisms of chemerin participating in vascular remodeling and whether Growth arrest-specific homeobox (Gax) can effectively intervene it remain obscured. Here, 3T3-F442A preadipocytes were cultured, injected into athymic mice to model fat pads, and treated respectively with Ad-chemerin, Ad-Gax, or specific inhibitors in vitro and in vivo. MTT, flow cytometry, Western blotting, and imunohisto(cyto)-chemistry analyses showed that chemerin enhanced the expression of FABP4 and VEGF, activated Akt/mTOR and ERK pathways, increased the cell percent of S phase, decreased the percent of G0-G1 phase and apoptotic cells, and augmented neovascular density in fat pads...
March 21, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28325885/physiological-frailty-index-pfi-quantitative-in-life-estimate-of-individual-biological-age-in-mice
#19
Marina P Antoch, Michelle Wrobel, Karen K Kuropatwinski, Ilya Gitlin, Katerina I Leonova, Ilia Toshkov, Anatoli S Gleiberman, Alan D Hutson, Olga B Chernova, Andrei V Gudkov
The development of healthspan-extending pharmaceuticals requires quantitative estimation of age-related progressive physiological decline. In humans, individual health status can be quantitatively assessed by means of a frailty index (FI), a parameter which reflects the scale of accumulation of age-related deficits. However, adaptation of this methodology to animal models is a challenging task since it includes multiple subjective parameters. Here we report a development of a quantitative non-invasive procedure to estimate biological age of an individual animal by creating physiological frailty index (PFI)...
March 19, 2017: Aging
https://www.readbyqxmd.com/read/28324785/-ub006-a-new-fatty-acid-synthase-inhibitor-and-cytotoxic-agent-without-anorexic-side-effects
#20
Kamil Makowski, Joan Francesc Mir, Paula Mera, Xavier Ariza, Guillermina Asins, Fausto G Hegardt, Laura Herrero, Jordi García, Dolors Serra
C75 is a synthetic anticancer drug that inhibits fatty acid synthase (FAS) and shows a potent anorexigenic side effect. In order to find new cytotoxic compounds that do not impact food intake, we synthesized a new family of C75 derivatives. The most promising anticancer compound among them was UB006 ((4SR,5SR)-4-(hydroxymethyl)-3-methylene-5-octyldihydrofuran-2(3H)-one). The effects of this compound on cytotoxicity, food intake and body weight were studied in UB006 racemic mixture and in both its enantiomers separately...
March 12, 2017: European Journal of Medicinal Chemistry
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