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Patient derived tissue slice culture treatment

Heike Niessner, Tobias Sinnberg, Corinna Kosnopfel, Keiran S M Smalley, Daniela Beck, Christian Praetorius, Marion Mai, Stefan Beissert, Dagmar Kulms, Martin Schaller, Claus Garbe, Keith T Flaherty, Dana Westphal, Ines Wanke, Friedegund Meier
Purpose: NRAS mutations in malignant melanoma are associated with aggressive disease requiring rapid antitumor intervention, but there is no approved targeted therapy for this subset of patients. In clinical trials, the MEK inhibitor (MEKi) binimetinib displayed modest antitumor activity, making combinations a requisite. In a previous study, the BRAF inhibitor (BRAFi) vemurafenib was shown to induce endoplasmic reticulum (ER) stress that together with inhibition of the RAF-MEK-ERK (MAPK) pathway amplified its proapoptotic activity in BRAF-mutant melanoma...
October 15, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Teun J de Vries, Ton Schoenmaker, Dimitra Micha, Jolanda Hogervorst, Siham Bouskla, Tim Forouzanfar, Gerard Pals, Coen Netelenbos, E Marelise W Eekhoff, Nathalie Bravenboer
Fibrodysplasia Ossificans Progressiva (FOP) is a progressive disease characterized by periods of heterotopic ossification of soft connective tissues, including ligaments. Though progress has been made in recent years in unraveling the underlying mechanism, patient-derived cell models are necessary to test potential treatment options. Periodontal ligament fibroblasts (PLF) from extracted teeth can be used to study deviant bone modeling processes in vitro since these cells are derived from genuine ligaments. They further provide a tool to study the hitherto unknown role of the bone morphogenesis protein receptor type 1 (BMPR-1) Activin A type 1 receptor ACVR1-R206H mutation in osteoclastogenesis...
July 10, 2017: Bone
Simona Nanni, Agnese Re, Cristian Ripoli, Aoife Gowran, Patrizia Nigro, Domenico D'Amario, Antonio Amodeo, Filippo Crea, Claudio Grassi, Alfredo Pontecorvi, Antonella Farsetti, Claudia Colussi
Aims: Beyond the control of nuclear-cytoplasmic trafficking nucleoporins regulate gene expression and are involved in cardiac diseases. Notably, a number of cardiovascular disorders have been linked to alterations in epigenetic mechanisms. Here we aimed to determine the contribution of Nup153 to the epigenetic alterations occurring in cardiomyopathy of dystrophin-deficient mdx mice (C57BL/10ScSn-Dmd mdx /J). Methods and results: Nup153 was lysine-acetylated and its expression was significantly increased at protein level in mdx hearts compared with controls...
November 1, 2016: Cardiovascular Research
Nicolette G Alkema, G Bea A Wisman, Ate G J van der Zee, Marcel A T M van Vugt, Steven de Jong
High-grade serous ovarian cancer (HGSOC) has the highest mortality rate among all gynecological cancers. Patients are generally diagnosed in an advanced stage with the majority of cases displaying platinum resistant relapses. Recent genomic interrogation of large numbers of HGSOC patient samples indicated high complexity in terms of genetic aberrations, intra- and intertumor heterogeneity and underscored their lack of targetable oncogenic mutations. Sub-classifications of HGSOC based on expression profiles, termed 'differentiated', 'immunoreactive', 'mesenchymal' and 'proliferative', were shown to have prognostic value...
January 2016: Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
Maria Veronica Russo, Alice Faversani, Stefano Gatti, Dario Ricca, Alessandro Del Gobbo, Stefano Ferrero, Alessandro Palleschi, Valentina Vaira, Silvano Bosari
INTRODUCTION: Lung cancer remains the leading cause of tumor-related deaths, despite advances in the understanding of the disease pathogenesis and in its clinical treatment. It is crucial to develop novel technologies to discover disease biomarkers and predict individual therapy response. MATERIALS AND METHODS: We established 48 patients-derived tumor xenografts (PDTXs) implanted in the subrenal capsule of immunodeficient mice using thin, precision-cut tumor tissue slices, derived from five patients affected by non-small cell lung cancer...
2015: Frontiers in Oncology
Candece L Gladson, Monica E Burgett, Justin D Lathia, Patrick Roth, Ping Huang, Amit Vasanji, Meizhang Li, Shideng Bao, Amy Nowacki, Jeremy N RIch, Michael Weller
BACKGROUND: A histologic characteristic of glioblastoma tumors (GBM) is angiogenesis, which requires endothelial cell (EC) sprouting and migration. This is thought to be facilitated by signals in a specialized microenvironment, the perivascular niche, where glioma stem cells (GSC) reside in proximity to ECs. The goal of this study was to determine whether ECs and GSCs directly interact, the mechanism by which this occurs, and the effect on EC signaling and function. METHODS: We utilized multi-label immunofluorescence of GBM tissue and of co-cultured ECs and GSCs to evaluate the proximity of ECs to GSCs and effect of this interaction on signaling, respectively...
July 2014: Neuro-oncology
Mutsuko Minata, Chunyu Gu, Kaushal Joshi, Mariko Nakano-Okuno, Christopher Hong, Chi-Hung Nguyen, Harley I Kornblum, Annie Molla, Ichiro Nakano
Glioblastoma multiforme (GBM) is a highly lethal brain tumor. Due to resistance to current therapies, patient prognosis remains poor and development of novel and effective GBM therapy is crucial. Glioma stem cells (GSCs) have gained attention as a therapeutic target in GBM due to their relative resistance to current therapies and potent tumor-initiating ability. Previously, we identified that the mitotic kinase maternal embryonic leucine-zipper kinase (MELK) is highly expressed in GBM tissues, specifically in GSCs, and its expression is inversely correlated with the post-surgical survival period of GBM patients...
2014: PloS One
Kayvan R Keshari, Renuka Sriram, Mark Van Criekinge, David M Wilson, Zhen J Wang, Daniel B Vigneron, Donna M Peehl, John Kurhanewicz
BACKGROUND: The treatment of prostate cancer has been impeded by the lack of both clinically relevant disease models and metabolic markers that track tumor progression. Hyperpolarized (HP) (13) C MR spectroscopy has emerged as a new technology to investigate the metabolic shifts in prostate cancer. In this study, we investigate the glucose reprogramming using HP (13) C pyruvate MR in a patient-derived prostate tissue slice culture (TSC) model. METHODS: The steady-state metabolite concentrations in freshly excised human prostate TSCs were assessed and compared to those from snap-frozen biopsy samples...
August 2013: Prostate
Timo Weiland, Kathrin Klein, Martina Zimmermann, Tobias Speicher, Sascha Venturelli, Alexander Berger, Heike Bantel, Alfred Königsrainer, Martin Schenk, Thomas S Weiss, Albrecht Wendel, Matthias Schwab, Michael Bitzer, Ulrich M Lauer
BACKGROUND: Tumor necrosis factor alpha (TNF) is able to kill cancer cells via receptor-mediated cell death requiring adenosine triphosphate (ATP). Clinical usage of TNF so far is largely limited by its profound hepatotoxicity. Recently, it was found in the murine system that specific protection of hepatocytes against TNF's detrimental effects can be achieved by fructose-mediated ATP depletion therein. Before employing this quite attractive selection principle in a first clinical trial, we here comprehensively investigated the interdependence between ATP depletion and TNF hepatotoxicity in both in vitro and ex vivo experiments based on usage of primary patient tissue materials...
2012: PloS One
Zhi-qiang Fei, Jian-yi Xiong, Lei Chen, Hui-yong Shen, Ngo Stephanie, Wang Jeffrey, Da-ping Wang
BACKGROUND: Treatments to regenerate different tissue involving the transplantation of bone marrow derived mesenchymal precursor cells are anticipated. Using an alternative methods, in vitro organotypic slice culture method, would be useful to transplant cells and assessing the effects. This study was to determine the possibility of differentiating human bone marrow precursor cells into cells of the neuronal lineage by transplanting into canine spinal cord organotypic slice cultures. METHODS: Bone marrow aspirates were obtained from posterior superior iliac spine (PSIS) of patients that had undergone spinal fusion due to a degenerative spinal disorder...
November 2012: Chinese Medical Journal
Ryan W Bonvillain, Svitlana Danchuk, Deborah E Sullivan, Aline M Betancourt, Julie A Semon, Michelle E Eagle, Jacques P Mayeux, Ashley N Gregory, Guangdi Wang, Ian K Townley, Zachary D Borg, Daniel J Weiss, Bruce A Bunnell
Currently, patients with end-stage lung disease are limited to lung transplantation as their only treatment option. Unfortunately, the lungs available for transplantation are few. Moreover, transplant recipients require life-long immune suppression to tolerate the transplanted lung. A promising alternative therapeutic strategy is decellularization of whole lungs, which permits the isolation of an intact scaffold comprised of innate extracellular matrix (ECM) that can theoretically be recellularized with autologous stem or progenitor cells to yield a functional lung...
December 2012: Tissue Engineering. Part A
Hiromitsu Moriya, Makoto Ohbu, Nobuyuki Kobayashi, Satoshi Tanabe, Natsuya Katada, Nobue Futawatari, Shinichi Sakuramoto, Shiro Kikuchi, Isao Okayasu, Masahiko Watanabe
BACKGROUND: Resected specimens of superficial squamous cell carcinoma of the esophagus (SSCCE) underwent D2-40 immunostaining to accurately assess lymphatic tumor emboli (LY) and to analyze correlations between LY and lymph node metastasis (N). This present study was designed to determine the accuracy of LY grade for predicting the risk of N. MATERIALS AND METHODS: We studied 75 patients with SSCCE who underwent surgical resection of their tumors. Resected specimens were sliced into continuous sections at 5 mm intervals...
September 2011: World Journal of Surgery
A A Hall, C C Leonardo, L A Collier, D D Rowe, A E Willing, K R Pennypacker
A major limitation of current stroke therapies is the need to treat candidate patients within 3 h of stroke onset. Human umbilical cord blood cell (HUCBC) and the sigma receptor agonist 1,3, di-o-tolylguanidine (DTG) administration both caused significant reductions in brain damage in the rat middle cerebral artery occlusion model of stroke when administered at delayed timepoints. In vivo, these treatments suppress the infiltration of peripheral lymphocytes into the brain in addition to decreasing neurodegeneration...
December 1, 2009: Neuroscience
Susanne Bürger, Monika Noack, Ludmil P Kirazov, Evgeni P Kirazov, Cyrill L Naydenov, Elena Kouznetsova, Yousef Yafai, Reinhard Schliebs
The up-regulation of the angiogenic vascular endothelial growth factor (VEGF) in brains of Alzheimer patients in close relationship to beta-amyloid (Abeta) plaques, suggests a link of VEGF action and processing of the amyloid precursor protein (APP). To reveal whether VEGF may affect APP processing, brain slices derived from 17-month-old transgenic Tg2576 mice were exposed with 1ng/ml VEGF for 6, 24, and 72h, followed by assessing cytosolic and membrane-bound APP expression, level of both soluble and fibrillar Abeta-peptides, as well as activities of alpha- and beta-secretases in brain slice tissue preparations...
October 2009: International Journal of Developmental Neuroscience
Philippe Taupin
The application is in the field of neural stem cells (NSCs) and cellular therapy. It aims to identify and characterize neural progenitor and stem cells from adult periodontal tissue. Neural progenitor and stem cells were isolated and characterized from periodontal tissue originating from biopsies of adult patients. Adult human periodontal-derived neural progenitor and stem cells can be induced to differentiate into neuronal and glial cells, osteoblasts and cells of the periodontium. They survive and integrate when transplanted into organotypic hippocampal slice cultures...
May 2009: Expert Opinion on Therapeutic Patents
S Giannini, R Buda, B Grigolo, F Vannini, L De Franceschi, A Facchini
OBJECTIVE: Autologous chondrocyte implantation (ACI) has been successfully used for the treatment of osteochondral lesions of the talus. One of the main problems of this surgical strategy is related to the harvesting of the cartilage slice from a healthy knee. The aim of this study was to examine the capacity of chondrocytes harvested from a detached osteochondral fragment to proliferate and to serve as a source of viable cells for ACI in the repair of ankle cartilage defects. METHODS: Detached osteochondral fragments harvested from the ankle joint of 20 patients with osteochondral lesions of the talus served as the source of human articular cartilage specimens...
July 2005: Osteoarthritis and Cartilage
M Meyer, J Johansen, J B Gramsbergen, T E Johansen, J Zimmer
Transplantation of embryonic nigral tissue is used as an experimental therapy for patients with Parkinson's disease but is hampered by a limited survival rate of dopaminergic neurons. Glial cell line-derived neurotrophic factor (GDNF) is a potent survival factor for nigrostriatal dopaminergic neurons, and the present in vitro study aimed at improving the survival of dopaminergic neurons in porcine mesencephalic brain slice cultures by adding transfected, immortalized, temperature-sensitive GDNF-releasing HiB5 cells (HiB5-GDNF)...
July 2000: Experimental Neurology
S Kotake, N Udagawa, N Takahashi, K Matsuzaki, K Itoh, S Ishiyama, S Saito, K Inoue, N Kamatani, M T Gillespie, T J Martin, T Suda
IL-17 is a newly discovered T cell-derived cytokine whose role in osteoclast development has not been fully elucidated. Treatment of cocultures of mouse hemopoietic cells and primary osteoblasts with recombinant human IL-17 induced the formation of multinucleated cells, which satisfied major criteria of osteoclasts, including tartrate-resistant acid phosphatase activity, calcitonin receptors, and pit formation on dentine slices. Direct interaction between osteoclast progenitors and osteoblasts was required for IL-17-induced osteoclastogenesis, which was completely inhibited by adding indomethacin or NS398, a selective inhibitor of cyclooxgenase-2 (COX-2)...
May 1999: Journal of Clinical Investigation
K Ostergaard, S A Jones, C Hyman, J Zimmer
Early postnatal rat brain tissue can be grown for several weeks as organotypic slice cultures by the roller-tube method. We have here used this method to study the effects of donor age and brain-derived neurotrophic factor (BDNF) on the survival and growth of tyrosine hydroxylase immunoreactive (TH-i), dopaminergic (DA) neurons during the postnatal period when their nerve fibers normally innervate the striatal target. Tissue slices of ventral mesencephalon (VM) and striatum were prepared from newborn and 7-day-old rats and cocultured for 3--3 1/2 weeks with different combinations of the two donor ages...
December 1996: Experimental Neurology
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