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Uday B Maachani, Uma Shankavaram, Tamalee Kramp, Philip J Tofilon, Kevin Camphausen, Anita T Tandle
Glioblastoma multiforme (GBM) continues to be the most frequently diagnosed and lethal primary brain tumor. Adjuvant chemo-radiotherapy remains the standard of care following surgical resection. In this study, using reverse phase protein arrays (RPPAs), we assessed the biological effects of radiation on signaling pathways to identify potential radiosensitizing molecular targets. We identified subsets of proteins with clearly concordant/discordant behavior between irradiated and non-irradiated GBM cells in vitro and in vivo...
October 14, 2016: Oncotarget
Jana Jakubikova, Danka Cholujova, Teru Hideshima, Paulina Gronesova, Andrea Soltysova, Takeshi Harada, Jungnam Joo, Sun-Young Kong, Raphael E Szalat, Paul G Richardson, Nikhil C Munshi, David M Dorfman, Kenneth C Anderson
Specific niches within the tumor bone marrow (BM) microenvironment afford a sanctuary for multiple myeloma (MM) clones due to stromal cell-tumor cell interactions, which confer survival advantage and drug resistance. Defining the sequelae of tumor cell interactions within the MM niches on an individualized basis may provide the rationale for personalized therapies. To mimic the MM niche, we here describe a new 3D co-culture ex-vivo model in which primary MM patient BM cells are co-cultured with mesenchymal stem cells (MSC) in a hydrogel 3D system...
October 13, 2016: Oncotarget
Yang Yu, Qingyun Zhang, Qinggui Meng, Chen Zong, Lei Liang, Xue Yang, Rui Lin, Yan Liu, Yang Zhou, Hongxiang Zhang, Xiaojuan Hou, Zhipeng Han, Jiwen Cheng
Prostate cancer (PCa) has become the second leading cause of male cancer-related mortality in the United States. Mesenchymal stem cells (MSCs) are able to migrate to tumor tissues, and are thus considered to be novel antitumor carriers. However, due to their immunosuppressive nature, the application of MSCs in PCa therapy remains limited. In this study, we investigated the effect of MSCs overexpressing an NAD-dependent deacetylase sirtuin 1 (MSCs-Sirt1) on prostate tumor growth, and we analyzed the underlying mechanisms...
October 18, 2016: Oncotarget
Vincent Le Coz, Chaobin Zhu, Aurore Devocelle, Aimé Vazquez, Claude Boucheix, Sandy Azzi, Cindy Gallerne, Pierre Eid, Séverine Lecourt, Julien Giron-Michel
Melanoma is a particularly virulent human cancer, due to its resistance to conventional treatments and high frequency of metastasis. Melanomas contain a fraction of cells, the melanoma-initiating cells (MICs), responsible for tumor propagation and relapse. Identification of the molecular pathways supporting MICs is, therefore, vital for the development of targeted treatments. One factor produced by melanoma cells and their microenvironment, insulin-like growth factor-1 (IGF- 1), is linked to epithelial-mesenchymal transition (EMT) and stemness features in several cancers...
October 18, 2016: Oncotarget
Astrid Escudero-Esparza, Michael Bartoschek, Chrysostomi Gialeli, Marcin Okroj, Sioned Owen, Karin Jirström, Akira Orimo, Wen G Jiang, Kristian Pietras, Anna M Blom
Human CUB and Sushi multiple domains 1 (CSMD1) is a membrane-bound complement inhibitor suggested to act as a putative tumor suppressor gene, since allelic loss of this region encompassing 8p23 including CSMD1 characterizes various malignancies. Here, we assessed the role of CSMD1 as a tumor suppressor gene in the development of breast cancer in vitro and in vivo. We found that human breast tumor tissues expressed CSMD1 at lower levels compared to that in normal mammary tissues. The decreased expression of CSMD1 was linked to a shorter overall survival of breast cancer patients...
October 18, 2016: Oncotarget
Maggie Y Jiang, Tammy L Lee, Su-Shin Hao, Sepi Mahooti, Stephen M Baird, Daniel J Donoghue, Martin Haas
Prostate Cancer represents the second leading cause of cancer death among men in the United States, and the third leading cause of cancer death among men in Europe. We have previously shown that cells possessing Cancer Stem Cell (CSC) characteristics can be grown from human PrCa tissue harvested at the time of prostatectomy. However, the cellular origin of these CSCs was not previously known. In most cases, simple hematoxylin and eosin (H&E) stained sections are sufficient to make a definitive diagnosis of prostatic adenocarcinoma (PrCa) in needle biopsy samples...
October 18, 2016: Oncotarget
Shehla Akbar, Fazal Subhan, Nasiara Karim, Muhammad Shahid, Nisar Ahmad, Gowhar Ali, Wajahat Mahmood, Khwaja Fawad
BACKGROUND: Diabetic neuropathy is the most prevalent, persistent and debilitating complication of diabetes mellitus often coupled with vulvodynia that may present as an isolated symptom or as a part of constellation of other neuropathic abnormalities. OBJECTIVE: Flavonoids have selective affinity for GABA receptors and 6-methoxyflavanone (6-MeOF) is a positive allosteric modulator of GABA responses at human recombinant GABAA receptors. GABAergic and opioidergic system inhibition have been shown to facilitate neuropathic pain...
October 17, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Yassine Ait-Bali, Saadia Ba-M'hamed, Mohammed Bennis
In the present work, we investigated developmental toxicity of Paraquat (PQ), from the 1st or 6th day of mating and throughout the gestation period. We have examined several parameters, including toxicity indices, reproductive performance, sensorimotor development, as well as anxiety and cognitive performance of the offspring. Our results showed that exposure to 20mg/kg of Paraquat during the first days of pregnancy completely prevents pregnancy in treated mice, but from the 6th day of pregnancy, an alteration in fertility and reproductive parameters was observed...
October 13, 2016: Environmental Toxicology and Pharmacology
Rodrigo Lopes de Lima, Rosenilde Carvalho de Holanda Afonso, Vivaldo Moura Neto, Ana Maria Bolognese, Marcos Fabio Henriques Dos Santos, Margareth Maria Gomes de Souza
OBJECTIVE: This study was conducted to identify and characterize dental follicle stem cells (DFSCs) by analyzing expression of embryonic, mesenchymal and neural stem cells surface markers. Design Dental follicle cells (DFCs) were evaluated by immunocytochemistry using embryonic stem cells markers (OCT4 and SOX2), mesenchmal stem cells (MSCs) markers (Notch1, active Notch1, STRO, CD44, HLA-ABC, CD90), neural stem cells markers (Nestin and β-III-tubulin), neural crest stem cells (NCSCs) markers (p75 and HNK1) and a glial cells marker (GFAP)...
October 8, 2016: Archives of Oral Biology
Clive J Curley, Eimear B Dolan, Brenton Cavanagh, Janice O'Sullivan, Garry P Duffy, Bruce P Murphy
Localized delivery of stem cells is potentially a promising therapeutic strategy for regenerating damaged myocardium. Many studies focus on limiting the biologic component of cell loss, but few address the contribution of mechanical factors. This study investigates optimal parameters for retaining the largest volume of cell loaded hydrogels post intramyocardial injection, without compromising cell viability. In vitro, hydrogel was injected into porcine hearts using various needle designs. Hydrogel retention and distribution pattern was then determined...
October 20, 2016: Journal of Biomedical Materials Research. Part B, Applied Biomaterials
Charlotte V Cox, Paraskevi Diamanti, John P Moppett, Allison Blair
A significant number of children with T-lineage acute lymphoblastic leukemia (T-ALL) fail to respond to therapy and experience early relapse. CD99 has been shown to be overexpressed on T-ALL cells and is considered to be a reliable detector of the disease. However, the relevance of CD99 overexpression in ALL has not been investigated in a functional context. The aim of this study was to investigate the functional capacity of CD99+ cells in childhood ALL and determine the suitability of CD99 as a therapeutic target...
2016: PloS One
Christoph Baldow, Lars Thielecke, Ingmar Glauche
The availability of several methods to unambiguously mark individual cells has strongly fostered the understanding of clonal developments in hematopoiesis and other stem cell driven regenerative tissues. While cellular barcoding is the method of choice for experimental studies, patients that underwent gene therapy carry a unique insertional mark within the transplanted cells originating from the integration of the retroviral vector. Close monitoring of such patients allows accessing their clonal dynamics, however, the early detection of events that predict monoclonal conversion and potentially the onset of leukemia are beneficial for treatment...
2016: PloS One
Al Shaimaa Hasan, Lan Luo, Chen Yan, Tian-Xia Zhang, Yoshishige Urata, Shinji Goto, Safwat A Mangoura, Mahmoud H Abdel-Raheem, Shouhua Zhang, Tao-Sheng Li
Cardiosphere-derived cells (CDCs), one of the promising stem cell sources for myocardial repair, have been tested in clinical trials and resulted in beneficial effects; however, the relevant mechanisms are not fully understood. In this study, we examined the hypothesis that CDCs favor heart repair by switching the macrophages from a pro-inflammatory phenotype (M1) into a regulatory anti-inflammatory phenotype (M2). Macrophages from mice were cultured with CDCs-conditioned medium or with fibroblasts-conditioned medium as a control...
2016: PloS One
Hai-Juan Liu, Hua Yan, Jun Yan, Hao Li, Liang Chen, Li-Ren Han, Xiao-Fei Yang
Spinal cord injury (SCI) causes a significant amount of bone loss, which results in osteoporosis (OP). The neuropeptide substance P (SP) and SP receptors may play important roles in the pathogenesis of OP after SCI. To identify the roles of SP in the bone marrow mesenchymal stem cell derived osteoblasts (BMSC-OB) in SCI rats, we investigated the expression of neurokinin-1 receptors (NK1R) in BMSC-OB and the effects of SP on bone formation by development of BMSC-OB cultures. Sixty young male Sprague-Dawley rats were randomized into two groups: SHAM and SCI...
2016: PloS One
Kishore Polireddy, Ruochen Dong, Peter R McDonald, Tao Wang, Brendan Luke, Ping Chen, Melinda Broward, Anuradha Roy, Qi Chen
BACKGROUND: Pancreatic cancer has an enrichment of stem-like cancer cells (CSCs) that contribute to chemoresistant tumors prone to metastasis and recurrence. Drug screening assays based on cytotoxicity cannot identify specific CSC inhibitors, because CSCs comprise only a small portion of cancer cell population, and it is difficult to propagate stable CSC populations in vitro for high-throughput screening (HTS) assays. Based on the important role of cancer cell epithelial-to-mesenchymal transition (EMT) in promoting CSCs, we hypothesized that inhibition of EMT can be a useful strategy for inhibiting CSCs, and therefore a feasible approach for HTS can be built for identification of CSC inhibitors, based on assays detecting EMT inhibition...
2016: PloS One
Masayuki Sano, Minoru Iijima, Manami Ohtaka, Mahito Nakanishi
Tissue-specific control of gene expression is an invaluable tool for studying various biological processes and medical applications. Efficient regulatory systems have been utilized to control transgene expression in various types of DNA viral or integrating viral vectors. However, existing regulatory systems are difficult to transfer into negative-strand RNA virus vector platforms because of significant differences in their transcriptional machineries. In this study, we developed a novel strategy for regulating transgene expression mediated by a cytoplasmic RNA vector based on a replication-defective and persistent Sendai virus (SeVdp)...
2016: PloS One
Kenichi Sasaki, Takeru Makiyama, Yoshinori Yoshida, Yimin Wuriyanghai, Tsukasa Kamakura, Suguru Nishiuchi, Mamoru Hayano, Takeshi Harita, Yuta Yamamoto, Hirohiko Kohjitani, Sayako Hirose, Jiarong Chen, Mihoko Kawamura, Seiko Ohno, Hideki Itoh, Ayako Takeuchi, Satoshi Matsuoka, Masaru Miura, Naokata Sumitomo, Minoru Horie, Shinya Yamanaka, Takeshi Kimura
INTRODUCTION: Human induced pluripotent stem cells (hiPSCs) offer a unique opportunity for disease modeling. However, it is not invariably successful to recapitulate the disease phenotype because of the immaturity of hiPSC-derived cardiomyocytes (hiPSC-CMs). The purpose of this study was to establish and analyze iPSC-based model of catecholaminergic polymorphic ventricular tachycardia (CPVT), which is characterized by adrenergically mediated lethal arrhythmias, more precisely using electrical pacing that could promote the development of new pharmacotherapies...
2016: PloS One
Mercedes Fernández-Moreno, Tamara Hermida-Gómez, M Esther Gallardo, Andrea Dalmao-Fernández, Ignacio Rego-Pérez, Rafael Garesse, Francisco J Blanco
INTRODUCTION: The generation of Rho-0 cells requires the use of an immortalization process, or tumor cell selection, followed by culture in the presence of ethidium bromide (EtBr), incurring the drawbacks its use entails. The purpose of this work was to generate Rho-0 cells using human mesenchymal stem cells (hMSCs) with reagents having the ability to remove mitochondrial DNA (mtDNA) more safely than by using EtBr. METHODOLOGY: Two immortalized hMSC lines (3a6 and KP) were used; 143B...
2016: PloS One
Jun Li, Wei Zhen, Dengkai Long, Ling Ding, Anhui Gong, Chenghong Xiao, Weike Jiang, Xiaoqing Liu, Tao Zhou, Luqi Huang
Pseudostellaria heterophylla (Miq.) Pax is a mild tonic herb widely cultivated in the Southern part of China. The tuberous roots of P. heterophylla accumulate high levels of secondary metabolism products of medicinal value such as saponins, flavonoids, and isoquinoline alkaloids. Despite numerous studies on the pharmacological importance and purification of these compounds in P. heterophylla, their biosynthesis is not well understood. In the present study, we used Illumina HiSeq 4000 sequencing platform to sequence the RNA from flowers, leaves, stem, root cortex and xylem tissues of P...
2016: PloS One
Ming-Sheng Lim, Jiang Huai Wang, Derek G Power, H Paul Redmond
The link between inflammation, immunity and cancer is well established. In the last decade, there has been considerable excitement over cancer stem cells, believed to be a subset of tumour cells responsible for their initiation, propagation and resistance to conventional chemoradiotherapy. In this review, we discuss the characterization of cancer stem cells and describe their modulation by inflammation with a focus on melanoma.
October 19, 2016: Melanoma Research
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