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https://www.readbyqxmd.com/read/28723516/the-molecular-evolution-of-castration-resistant-prostate-cancer
#1
REVIEW
Yvonne Ceder, Anders Bjartell, Zoran Culig, Mark A Rubin, Scott Tomlins, Tapio Visakorpi
CONTEXT: Androgen deprivation therapy (ADT) is the backbone of treatment for advanced prostate cancer. However, castration-resistant prostate cancer (CRPC) nearly invariably develops through a range of different molecular mechanisms accompanied by progression to a more aggressive phenotype. OBJECTIVE: To understand the key molecular mechanisms leading to CRPC and the functional implications of this progression. Understanding molecular evolutionary mechanisms in CRPC is essential for the development of novel curative therapeutic approaches...
December 2016: European Urology Focus
https://www.readbyqxmd.com/read/28719907/tumor-heterogeneity-in-lymphomas-a-different-breed
#2
Christian M Schürch, Birgit Federmann, Leticia Quintanilla-Martinez, Falko Fend
The facts that cancer represents tissues consisting of heterogeneous neoplastic, as well as reactive, cell populations and that cancers of the same histotype may show profound differences in clinical behavior have long been recognized. With the advent of new technologies and the demands of precision medicine, the investigation of tumor heterogeneity has gained much interest. An understanding of intertumoral heterogeneity in patients with the same disease entity is necessary to optimally guide personalized treatment...
July 19, 2017: Pathobiology: Journal of Immunopathology, Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28718381/histological-and-immunohistochemical-characterization-of-the-similarity-and-difference-between-ovarian-endometriomas-and-deep-infiltrating-endometriosis
#3
Xishi Liu, Qi Zhang, Sun-Wei Guo
Ovarian endometrioma (OMA) and deep infiltrating endometriosis (DIE) have long been recognized to have different histology and, as such, postulated to be 2 separate disease entities. Few studies, however, have attempted to elucidate the causes for their differences. Making use of ectopic endometrial tissue samples from 25 and 20 women with OMA and DIE, respectively, and control endometrial tissue samples from 25 women without endometriosis, we conducted an immunohistochemical analysis to evaluate the expression of a group of carefully chosen markers for epithelial-mesenchymal transition (EMT), fibroblast-to-myofibroblast transdifferentiation (FMT), smooth muscle metaplasia (SMM), fibrosis, vascularity, hormonal receptors, and proteins involved in epigenetic modifications...
January 1, 2017: Reproductive Sciences
https://www.readbyqxmd.com/read/28717251/transdifferentiated-human-vascular-smooth-muscle-cells-are-a-new-potential-cell-source-for-endothelial-regeneration
#4
Xuechong Hong, Andriana Margariti, Alexandra Le Bras, Laureen Jacquet, Wei Kong, Yanhua Hu, Qingbo Xu
Endothelial dysfunction is widely implicated in cardiovascular pathological changes and development of vascular disease. In view of the fact that the spontaneous endothelial cell (EC) regeneration is a slow and insufficient process, it is of great interest to explore alternative cell sources capable of generating functional ECs. Vascular smooth muscle cell (SMC) composes the majority of the vascular wall and retains phenotypic plasticity in response to various stimuli. The aim of this study is to test the feasibility of the conversion of SMC into functional EC through the use of reprogramming factors...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28713614/condition-medium-of-cerebrospinal-fluid-and-retinoic-acid-induces-the-transdifferentiation-of-human-dental-pulp-stem-cells-into-neuroglia-and-neural-like-cells
#5
Sara Haratizadeh, Maryam Nazm Bojnordi, Shahram Darabi, Narges Karimi, Mehrdad Naghikhani, Hatef Ghasemi Hamidabadi, Morteza Seifi
Cerebrospinal fluid (CSF) contains several molecules which are essential for neurogenesis. Human dental pulp stem cells (hDPSCs) are putatively neural crest cell-derived that can differentiate into neurons and glial cells under appropriate neurotrophic factors. The aim of this study was to induce differentiation of hDPSCs into neuroglial phenotypes using retinoic acid (RA) and CSF. The hDPSCs from an impacted third molar were isolated by mechanical and digestion and cultured. The cells have treated by 10(-7) µM RA (RA group) for 8 days, 10% CSF (CSF group) for 8 days and RA with CSF for 8 days (RA/CSF group)...
June 2017: Anatomy & Cell Biology
https://www.readbyqxmd.com/read/28698932/small-molecules-for-reprogramming-and-transdifferentiation
#6
REVIEW
Hua Qin, Andong Zhao, Xiaobing Fu
Pluripotency reprogramming and transdifferentiation induced by transcription factors can generate induced pluripotent stem cells, adult stem cells or specialized cells. However, the induction efficiency and the reintroduction of exogenous genes limit their translation into clinical applications. Small molecules that target signaling pathways, epigenetic modifications, or metabolic processes can regulate cell development, cell fate, and function. In the recent decade, small molecules have been widely used in reprogramming and transdifferentiation fields, which can promote the induction efficiency, replace exogenous genes, or even induce cell fate conversion alone...
July 11, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28694020/transdifferentiation-of-brain-derived-neurotrophic-factor-bdnf-secreting-mesenchymal-stem-cells-significantly-enhance-bdnf-secretion-and-schwann-cell-marker-proteins
#7
Metzere Bierlein De la Rosa, Anup D Sharma, Surya K Mallapragada, Donald S Sakaguchi
The use of genetically modified mesenchymal stem cells (MSCs) is a rapidly growing area of research targeting delivery of therapeutic factors for neuro-repair. Cells can be programmed to hypersecrete various growth/trophic factors such as brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), and nerve growth factor (NGF) to promote regenerative neurite outgrowth. In addition to genetic modifications, MSCs can be subjected to transdifferentiation protocols to generate neural cell types to physically and biologically support nerve regeneration...
July 7, 2017: Journal of Bioscience and Bioengineering
https://www.readbyqxmd.com/read/28692939/oligomeric-proanthocyanidin-derived-from-grape-seeds-inhibited-nf-%C3%AE%C2%BAb-signaling-in-activated-hsc-involvement-of-jnk-erk-mapk-and-pi3k-akt-pathways
#8
Min Jiang, Yan-Ling Wu, Xia Li, Yu Zhang, Kai-Li Xia, Ben-Wen Cui, Li-Hua Lian, Ji-Xing Nan
In current study, we aimed to reveal the potential antifibrotic effects of oligomeric proanthocyanidin (OPC) from grape seeds on lipopolysaccharide (LPS)-activated, HSC-T6, a rat hepatic stellate cell line. HSC-T6 cells were treated with OPC 1h prior to LPS, and then incubated for indicated time. OPC inhibited cells viability of HSC-T6 cells and decrease protein expression of collagen I, α-smooth muscle actin (α-SMA), tissue inhibitors of metalloproteinases I (TIMP-1) on LPS-induced HSC-T6 cells. OPC also significantly inhibited phosphorylation of LPS-stimulated phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt), extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK)...
July 7, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28687009/post-surgery-fluids-promote-transition-of-cancer-stem-cell-to-endothelial-and-akt-mtor-activity-contributing-to-relapse-of-giant-cell-tumors-of-bone
#9
Flavio Fazioli, Gianluca Colella, Roberta Miceli, Mariano Giuseppe Di Salvatore, Michele Gallo, Serena Boccella, Annarosaria De Chiara, Carlo Ruosi, Filomena de Nigris
Giant cell tumors of bone (GCTB) are rare sarcomas with a high rate of unpredictable local relapse. Studies suggest that surgical methods affect recurrence, supporting the idea that local disease develops from re-growth of residual cancer cells. To identify early prognostic markers of individual risk of recurrence, we evaluated the effect of post-surgery fluids from a cohort of GCTB patients on growth of primary and established sarcoma cell lines, and mice xenographts. Post-surgery fluids increased cell growth and enhanced expression of CD44++, the principal receptor for the extracellular matrix component hyaluronan and the mesenchymal stem marker CD117+...
June 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28685927/altering-equine-corneal-fibroblast-differentiation-through-smad-gene-transfer
#10
Todd L Marlo, Elizabeth A Giuliano, Ratnakar Tripathi, Ajay Sharma, Rajiv R Mohan
OBJECTIVE: To explore the impact of equine corneal fibroblast (ECF) to myofibroblast (ECM) differentiation by altering the expression of the Smad genes either individually or in combination. Specifically, we sought to examine the ECF differentiation after (a) silencing of Smad2, 3, and 4 profibrotic genes individually and (b) overexpression of antifibrotic Smad7 gene and in a combination with pro- and antifibrotic Smad genes. METHODS: Equine corneal fibroblast primary cultures were generated as previously described...
July 6, 2017: Veterinary Ophthalmology
https://www.readbyqxmd.com/read/28684411/the-path-of-most-resistance-transdifferentiation-underlies-exceptional-nonresponses-to-androgen-receptor-pathway-inhibition-in-prostate-cancer
#11
Seema Sinha, Peter S Nelson
In this issue of Cancer Discovery, Zou and colleagues describe a mechanism involving cellular transdifferentiation that promotes exceptional resistance to antiandrogen therapy in prostate cancer. A background of coinactivation of Trp53 and Pten increased the frequency of the transdifferentiated neuroendocrine phenotype. These findings have implications for developing approaches to repress cellular plasticity and overcome treatment resistance. Cancer Discov; 7(7); 673-4. ©2017 AACRSee related article by Zou et al...
July 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28680125/regulation-of-retinal-pigment-epithelial-cell-phenotype-by-annexin-a8
#12
Katharina Lueck, Amanda-Jayne F Carr, Dimitrios Stampoulis, Volker Gerke, Ursula Rescher, John Greenwood, Stephen E Moss
The retinoic acid derivative fenretinide (FR) is capable of transdifferentiating cultured retinal pigment epithelial (RPE) cells towards a neuronal-like phenotype, but the underlying mechanisms are not understood. To identify genes involved in this process we performed a microarray analysis of RPE cells pre- and post-FR treatment, and observed a marked down-regulation of AnnexinA8 (AnxA8) in transdifferentiated cells. To determine whether AnxA8 plays a role in maintaining RPE cell phenotype we directly manipulated AnxA8 expression in cultured and primary RPE cells using siRNA-mediated gene suppression, and over-expression of AnxA8-GFP in conjunction with exposure to FR...
July 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28679560/histone-deacetylase-1-depletion-activates-human-cardiac-mesenchymal-stromal-cell-proangiogenic-paracrine-signaling-through-a-mechanism-requiring-enhanced-basic-fibroblast-growth-factor-synthesis-and-secretion
#13
Joseph B Moore, John Zhao, Annalara G Fischer, Matthew C L Keith, David Hagan, Marcin Wysoczynski, Roberto Bolli
BACKGROUND: Cardiac mesenchymal cell (CMC) administration improves cardiac function in animal models of heart failure. Although the precise mechanisms remain unclear, transdifferentiation and paracrine signaling are suggested to underlie their cardiac reparative effects. We have shown that histone deacetylase 1 (HDAC1) inhibition enhances CMC cardiomyogenic lineage commitment. Here, we investigated the impact of HDAC1 on CMC cytokine secretion and associated paracrine-mediated activities on endothelial cell function...
July 5, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28678785/dependency-of-a-therapy-resistant-state-of-cancer-cells-on-a-lipid-peroxidase-pathway
#14
Vasanthi S Viswanathan, Matthew J Ryan, Harshil D Dhruv, Shubhroz Gill, Ossia M Eichhoff, Brinton Seashore-Ludlow, Samuel D Kaffenberger, John K Eaton, Kenichi Shimada, Andrew J Aguirre, Srinivas R Viswanathan, Shrikanta Chattopadhyay, Pablo Tamayo, Wan Seok Yang, Matthew G Rees, Sixun Chen, Zarko V Boskovic, Sarah Javaid, Cherrie Huang, Xiaoyun Wu, Yuen-Yi Tseng, Elisabeth M Roider, Dong Gao, James M Cleary, Brian M Wolpin, Jill P Mesirov, Daniel A Haber, Jeffrey A Engelman, Jesse S Boehm, Joanne D Kotz, Cindy S Hon, Yu Chen, William C Hahn, Mitchell P Levesque, John G Doench, Michael E Berens, Alykhan F Shamji, Paul A Clemons, Brent R Stockwell, Stuart L Schreiber
Plasticity of the cell state has been proposed to drive resistance to multiple classes of cancer therapies, thereby limiting their effectiveness. A high-mesenchymal cell state observed in human tumours and cancer cell lines has been associated with resistance to multiple treatment modalities across diverse cancer lineages, but the mechanistic underpinning for this state has remained incompletely understood. Here we molecularly characterize this therapy-resistant high-mesenchymal cell state in human cancer cell lines and organoids and show that it depends on a druggable lipid-peroxidase pathway that protects against ferroptosis, a non-apoptotic form of cell death induced by the build-up of toxic lipid peroxides...
July 5, 2017: Nature
https://www.readbyqxmd.com/read/28674676/hypothesis-about-transdifferentiation-as-backbone-of-malignancy
#15
Jean Piechowski
BACKGROUND: Cancer is mainly watched through the prism of random mutations and related corruption of signaling pathways. However, it would seem puzzling to explain the tumor organization, pugnacity and steady evolution of the tumorous disease and, moreover, a systematic ascendancy over the healthy tissues, only through stochastic genomic alterations. MALIGNANCY SPECIFIC PROPERTIES: Considering the core characteristics of cancer cells, it appears that two major sets of properties are emerging, corresponding to well-identified physiological phenotypes, i...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28673439/-neuroendocrine-prostate-cancer-natural-history-molecular-features-therapeutic-management-and-future-directions
#16
Luca Campedel, Myriam Kossaï, Paul Blanc-Durand, Morgan Rouprêt, Thomas Seisen, Eva Compérat, Jean-Philippe Spano, Gabriel Malouf
Neuroendocrine prostate cancer is a rare malignancy with a an adverse prognostic. Histologically, It can be pure (small cells or large cells neuroendocrine carcinoma) or mixed with a adenocarcinoma component. Rarely diagnosed de novo, neuroendocrine prostate cancer is generally associated with advanced stage disease resistant to castration. As such, this histological subtype could represent an aggressive evolution of prostatic adenocarcinoma, through the epithelio-neuroendocrine transdifferentiation mechanism (phenomenon of lineage plasticity)...
June 30, 2017: Bulletin du Cancer
https://www.readbyqxmd.com/read/28671339/role-of-erbb-her-family-of-receptor-tyrosine-kinases-in-cholangiocyte-biology
#17
REVIEW
Anna Pellat, Javier Vaquero, Laura Fouassier
The ErbB/HER family comprises four distinct tyrosine kinase receptors, EGFR/ErbB1/HER1, ErbB2/HER2, ErbB3/HER3 and ErbB4/HER4, which trigger intracellular signals at the origin of essential cellular functions including differentiation, proliferation, survival and migration. Epithelial cells, named cholangiocytes, that line intrahepatic and extrahepatic bile ducts, contribute substantially to biliary secretory functions and bile transport. Although ErbB receptors have been widely studied in cholangiocarcinoma (CCA), a malignancy of the biliary tract, knowledge of these receptors in biliary epithelium physiology and in non-malignant cholangiopathies is far from completed...
July 3, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28670298/in-vitro-differentiation-of-preosteoblast-like-cells-mc3t3-e1-to-adipocytes-is-enhanced-by-1-25-oh-2-vitamin-d3
#18
Elisha Pendleton, Nalini Chandar
Osteoblasts and adipocytes originate from common mesenchymal progenitor cells and are controlled by specific transcription factors. While 1,25-dihydroxyvitamin D3 (vitamin D) is known to be an important factor for osteoblast differentiation, there are conflicting reports regarding its effect on adipogenesis. In this study, we attempted to understand the effect of exposure of preosteoblasts (MC3T3-E1) to adipogenic media with and without vitamin D and determined the expression of adipogenic genes during this process...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28667100/interleukin-10-inhibits-bone-marrow-fibroblast-progenitor-cell-mediated-cardiac-fibrosis-in-pressure-overloaded-myocardium
#19
Suresh K Verma, Venkata N S Garikipati, Prasanna Krishnamurthy, Sarah M Schumacher-Bass, Laurel A Grisanti, Maria Cimini, Zhongjian Cheng, Mohsin Khan, Yujia Yue, Cindy L Benedict, May M Truongcao, Joseph E Rabinowitz, David A Goukassian, Douglas G Tilley, Walter J Koch, Raj Kishore
Background -Activated fibroblasts (myofibroblasts; myoFBs) play critical role in cardiac fibrosis; however, their origin in the diseased heart remains unclear warranting further investigation. Recent studies suggest the contribution of bone marrow fibroblast progenitor cells (BM-FPC) in pressure overload (PO)-induced cardiac fibrosis. We have earlier shown that interleukin-10 (IL10) suppresses PO-induced cardiac fibrosis; however, the role of IL10 in inhibition of BM-FPC-mediated cardiac fibrosis is not known...
June 30, 2017: Circulation
https://www.readbyqxmd.com/read/28667074/lsd1-inhibitor-t-3775440-inhibits-sclc-cell-proliferation-by-disrupting-lds1-interactions-with-snag-domain-proteins-insm1-and-gfi1b
#20
Shinji Takagi, Yoshinori Ishikawa, Akio Mizutani, Shinji Iwasaki, Satoru Matsumoto, Yusuke Kamada, Toshiyuki Nomura, Kazuhide Nakamura
T-3775440 is an irreversible inhibitor of the chromatin demethylase LSD1, which exerts anti-proliferative effects by disrupting the interaction between LSD1 and GFI1B, a SNAG domain transcription factor, inducing leukemia cell transdifferentiation. Here we describe the anti-cancer effects and mechanism of action of T-3775440 in small cell lung cancer (SCLC). T-3775440 inhibited proliferation of SCLC cells in vitro and retarded SCLC tumor growth in vivo T-3775440 disrupted the interaction between LSD1 and the transcriptional repressor INSM1, thereby inhibiting expression of neuroendocrine-associated genes such as ASCL1...
June 30, 2017: Cancer Research
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