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Stem cells and clinical trials

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https://read.qxmd.com/read/30888664/advancements-in-managing-intracerebral-hemorrhage-transition-from-nihilism-to-optimism
#1
Sunil Munakomi, Amit Agrawal
There have been significant advancements in the management of intracerebral hemorrhage (ICH) stemming from new knowledge on its pathogenesis. Major clinical trials, such as Surgical Trial in Lobar Intracerebral Hemorrhage (STICH I and II), have shown only a small, albeit clinically relevant, advantage of surgical interventions in specific subsets of patients suffering from ICH. Currently, the aim is to use a minimally invasive and safe trajectory in removing significant brain hematomas with the aid of neuro-endoscopy or precise guidance through neuro-navigation, thereby avoiding a collateral damage to the surrounding normal brain tissue...
March 20, 2019: Advances in Experimental Medicine and Biology
https://read.qxmd.com/read/30887856/the-use-of-stromal-vascular-fraction-svf-platelet-rich-plasma-prp-and-stem-cells-in-the-treatment-of-osteoarthritis-an-overview-of-clinical-trials
#2
Sahar Mehranfar, Isa Abdi Rad, Ebrahim Mostafav, Abolfazl Akbarzadeh
Osteoarthritis (OA) is a major cause of disability across the world, which its prevalence is relatively high in elder population. Current accepted therapies such as exercise, anti-inflammatory drugs and intra-articular inoculation of corticosteroids are aimed at controlling symptoms in the affected patients. Surgical options including arthroplasty, osteotomy and joint replacement are other choices of treatment, which are invasive and can be applied in case of failure of conventional therapies. In the last few decades, efforts to treat musculoskeletal diseases are being increasingly focused on regenerative cellular therapies...
December 2019: Artificial Cells, Nanomedicine, and Biotechnology
https://read.qxmd.com/read/30887841/immune-checkpoint-based-therapy-in-myeloid-malignancies-a-promise-yet-to-be-fulfilled
#3
Jan Philipp Bewersdorf, Maximilian Stahl, Amer M Zeidan
Immune system evasion is essential for tumor cell survival and is mediated by the immunosuppressive tumor microenvironment and the activation of inhibitory immune checkpoints. While immune checkpoint-based therapy yielded impressive results in several advanced solid malignancies such as melanoma and non-small cell lung cancer, its role in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) is still evolving. Areas covered: Here we review the immunology in the tumor microenvironment in the bone marrow and discuss the current preclinical and clinical data for immune checkpoint-based therapy in myeloid neoplasms...
March 19, 2019: Expert Review of Anticancer Therapy
https://read.qxmd.com/read/30887712/concise-review-boosting-t-cell-reconstitution-following-allogeneic-transplantation-current-concepts-and-future-perspectives
#4
REVIEW
Laura Simons, Marina Cavazzana, Isabelle André
Allogeneic hematopoietic stem cell transplantation (HSCT) is the treatment of choice for a large number of malignant and nonmalignant (inherited) diseases of the hematopoietic system. Nevertheless, non-HLA identical transplantations are complicated by a severe T cell immunodeficiency associated with a high rate of infection, relapse and graft-versus-host disease. Initial recovery of T cell immunity following HSCT relies on peripheral expansion of memory T cells mostly driven by cytokines. The reconstitution of a diverse, self-tolerant, and naive T cell repertoire, however, may take up to 2 years and crucially relies on the interaction of T cell progenitors with the host thymic epithelium, which may be altered by GvHD, age or transplant-related toxicities...
March 18, 2019: Stem Cells Translational Medicine
https://read.qxmd.com/read/30887470/the-clinical-and-cost-effectiveness-of-inotuzumab-ozogamicin-for-the-treatment-of-adult-relapsed-or-refractory-b-cell-acute-lymphoblastic-leukaemia-an-evidence-review-group-evaluation-of-a-nice-single-technology-appraisal
#5
REVIEW
Edward Cox, Ros Wade, Mathilde Peron, Kristina Charlotte Dietz, Alison Eastwood, Stephen Palmer, Susan Griffin
The National Institute for Health and Care Excellence (NICE) invited Pfizer, the manufacturer of inotuzumab ozogamicin (henceforth inotuzumab), to submit clinical- and cost-effectiveness evidence for inotuzumab as part of NICE's single technology appraisal process. The Centre for Reviews and Dissemination and the Centre for Health Economics, both at the University of York, were commissioned as the independent evidence review group (ERG). The clinical-effectiveness data were from a multicentre randomised controlled trial that compared inotuzumab with standard of care (SoC), where SoC was the investigator's choice of chemotherapy...
March 19, 2019: PharmacoEconomics
https://read.qxmd.com/read/30887012/controversies-in-the-treatment-of-classical-hodgkin-lymphoma
#6
Dennis A Eichenauer, Marc André, Peter Johnson, Alexander Fossa, Olivier Casasnovas, Andreas Engert
Hodgkin lymphoma (HL) is a B-cell-derived malignancy that mostly affects young adults. Pathologically, HL is divided into classical HL (cHL) and the rare entity of nodular lymphocyte-predominant HL. Classical HL is characterized by few malignant cells termed Hodgkin and Reed-Sternberg cells embedded in an inflammatory background. The treatment of cHL has consistently improved over the last decades so that current standard approaches result in long-term remission rates in excess of 80%. However, potentially lethal therapy-related late complications affect an increasing number of survivors...
October 2018: Hemasphere
https://read.qxmd.com/read/30884856/hypoxia-regulated-mirnas-in-human-mesenchymal-stem-cells-exploring-the-regulatory-effects-in-ischemic-disorders
#7
Carmela Dell'Aversana, Francesca Cuomo, Chiara Botti, Ciro Maione, Annamaria Carissimo, Amelia Casamassimi, Lucia Altucci, Gilda Cobellis
Human mesenchymal/stromal stem cells (hMSC) are the most promising cell source for adult cell therapies in regenerative medicine. Many clinical trials have reported the use of autologous transplantation of hMSCs in several disorders, but with limited results. To exert their potential, hMSCs could exhibit efficient homing and migration toward lesion sites among other effects, but the underlying process is not clear enough. To further increase the knowledge, we studied the co-regulation between hypoxia-regulated genes and miRNAs...
March 16, 2019: International Journal of Molecular Sciences
https://read.qxmd.com/read/30879266/pre-and-post-transplant-ponatinib-for-a-patient-with-acute-megakaryoblastic-blast-phase-chronic-myeloid-leukemia-with-t315i-mutation-who-underwent-allogeneic-hematopoietic-stem-cell-transplantation
#8
Hirokazu Sasaki, Sachiko Mitani, Shigeru Kusumoto, Yoshiaki Marumo, Arisa Asano, Takashi Yoshida, Tomoko Narita, Asahi Ito, Hiroki Yano, Masaki Ri, Takashi Ishida, Hirokazu Komatsu, Shinsuke Iida
A 42-year-old female complaining of fever and night sweats was diagnosed with acute megakaryoblastic blast phase chronic myeloid leukemia (CML-BP). She had massive splenomegaly, left pleural effusion with leukemia infiltration, and moderate myelofibrosis. She received dasatinib monotherapy (140 mg/day) as for induction, after which her pleural effusion rapidly resolved and hematological remission was achieved. However, CML relapsed 4 months after starting dasatinib due to increased BCR-ABL fusion signals in the peripheral blood...
March 16, 2019: International Journal of Hematology
https://read.qxmd.com/read/30878561/therapy-for-glioblastoma-is-it-working
#9
REVIEW
Edward D Zanders, Fredrik Svensson, David S Bailey
Glioblastoma (GBM) remains one of the most intransigent of cancers, with a median overall survival of only 15 months after diagnosis. Drug treatments have largely proven ineffective; it is thought that this is related to the heterogeneous nature and plasticity of GBM-initiating stem cell lineages. Although many combination drug therapies are being positioned to address tumour heterogeneity, the most promising therapeutic approaches for GBM to date appear to be those targeting GBM by vaccination or antibody- and cell-based immunotherapy...
March 13, 2019: Drug Discovery Today
https://read.qxmd.com/read/30878384/in-vivo-safety-profile-and-biodistribution-of-gmp-manufactured-human-skin-derived-abcb5-positive-mesenchymal-stromal-cells-for-use-in-clinical-trials
#10
Nils Tappenbeck, Hannes M Schröder, Elke Niebergall-Roth, Fathema Hassinger, Ulf Dehio, Kathrin Dieter, Korinna Kraft, Andreas Kerstan, Jasmina Esterlechner, Natasha Y Frank, Karin Scharffetter-Kochanek, George F Murphy, Dennis P Orgill, Joachim Beck, Markus H Frank, Christoph Ganss, Mark A Kluth
BACKGROUND AIMS: Human dermal ABCB5-expressing mesenchymal stromal cells (ABCB5+ MSCs) represent a promising candidate for stem cell-based therapy of various currently uncurable diseases in several fields of regenerative medicine. We have developed and validated a method to isolate, from human skin samples, and expand ABCB5+ MSCs that meet the guideline criteria of the International Society for Cellular Therapy. We are able to process these cells into a Good Manufacturing Practice-conforming, MSC-based advanced-therapy medicinal product...
March 14, 2019: Cytotherapy
https://read.qxmd.com/read/30878319/effect-of-increased-dose-of-total-body-irradiation-on-graft-failure-associated-with-hla-haploidentical-transplantation-in-patients-with-severe-haemoglobinopathies-a-prospective-clinical-trial
#11
Javier Bolaños-Meade, Kenneth R Cooke, Christopher J Gamper, Syed Abbas Ali, Richard F Ambinder, Ivan M Borrello, Ephraim J Fuchs, Douglas E Gladstone, Christian B Gocke, Carol Ann Huff, Leo Luznik, Lode J Swinnen, Heather J Symons, Stephanie A Terezakis, Nina Wagner-Johnston, Richard J Jones, Robert A Brodsky
BACKGROUND: Although severe haemoglobinopathies can be cured with allogeneic blood or bone marrow transplantation, availability of matched donors and toxic effects can be problematic. We previously found that non-myeloablative haploidentical related bone marrow transplantation with post-transplantation cyclophosphamide expanded the donor pool while limiting graft-versus-host disease (GVHD). However, graft failure-albeit with full host haemopoietic recovery-occurred in 50% of patients...
March 13, 2019: Lancet Haematology
https://read.qxmd.com/read/30876928/changes-in-immunosuppressive-treatment-of-chronic-graft-versus-host-disease-comparison-of-2-surveys-within-allogeneic-hematopoietic-stem-cell-transplant-centers-in-germany-austria-and-switzerland
#12
D Wolff, I Hilgendorf, E Wagner-Drouet, Z Jedlickova, F Ayuk, R Zeiser, K Schäfer-Eckart, A Gerbitz, M Stadler, S Klein, J-M Middeke, A Lawitschka, J Winkler, J Halter, E Holler, G Kobbe, M Stelljes, M Ditschkowski, H Greinix
Chronic graft-versus-host disease (cGvHD) remains the leading cause of late morbidity and mortality. Despite the growing number of treatment options in cGvHD evidence remains sparse. The German-Austrian-Swiss GvHD Consortium performed a survey on clinical practice in treatment of cGvHD among transplant centers in Germany, Austria and Switzerland in 2009 and 2018 and compared the results. The survey performed in 2009 contained 20 questions on 1st line treatment and related issues and 4 questions on 2nd line scenarios followed by a survey on all systemic and topic treatment options known and applied with 31/36 (86%) transplant centers responding...
March 12, 2019: Biology of Blood and Marrow Transplantation
https://read.qxmd.com/read/30875083/human-pluripotent-stem-cell-derived-models-and-drug-screening-in-cns-precision-medicine
#13
REVIEW
M Catarina Silva, Stephen J Haggarty
Development of effective therapeutics for neurological disorders has historically been challenging partly because of lack of accurate model systems in which to investigate disease etiology and test new therapeutics at the preclinical stage. Human stem cells, particularly patient-derived induced pluripotent stem cells (iPSCs) upon differentiation, have the ability to recapitulate aspects of disease pathophysiology and are increasingly recognized as robust scalable systems for drug discovery. We review advances in deriving cellular models of human central nervous system (CNS) disorders using iPSCs along with strategies for investigating disease-relevant phenotypes, translatable biomarkers, and therapeutic targets...
March 15, 2019: Annals of the New York Academy of Sciences
https://read.qxmd.com/read/30873568/evaluation-of-intravenously-delivered-allogeneic-mesenchymal-stem-cells-for-treatment-of-elbow-osteoarthritis-in-dogs-a-pilot-study
#14
Anastasia Olsen, Valerie Johnson, Tracy Webb, Kelly S Santangelo, Steven Dow, Felix M Duerr
OBJECTIVES:  The aim of this study was to evaluate the safety and collect pilot data measuring clinical effects of intravenously administered, adipose-derived, culture-expanded, allogeneic mesenchymal stem cells in dogs with elbow osteoarthritis. MATERIALS AND METHODS:  Dogs ( n  = 13) with naturally occurring elbow osteoarthritis received three intravenous doses of allogeneic canine mesenchymal stem cells via an open-label clinical trial. Primary outcome measures collected over a 6-month study period included objective gait analysis, accelerometry, owner questionnaires and joint fluid analysis...
March 14, 2019: Veterinary and Comparative Orthopaedics and Traumatology: V.C.O.T
https://read.qxmd.com/read/30873530/fibroblasts-derived-from-human-adipose-stem-cells-produce-more-effective-extracellular-matrix-and-migrate-faster-compared-to-primary-dermal-fibroblasts
#15
Robert P Gersch, Jeffrey C Raum, Catherine E Calvert, Ivona Percec
BACKGROUND: The efficacy of adipose-derived stem cells (ASCs) to improve wound healing has been extensively investigated. Unfortunately, there have been no consistent reports describing significant improvements in healing time or outcomes in large-scale clinical trials using human ASCs. Primarily, these studies examined undifferentiated ASCs as opposed to specific cells differentiated from ASCs. OBJECTIVE: Here, we examine the properties of fibroblasts differentiated from human ASCs (dFib cells) in comparison to those of primary dermal fibroblasts...
March 15, 2019: Aesthetic Surgery Journal
https://read.qxmd.com/read/30871903/the-role-of-bone-marrow-aspirate-concentrate-for-the-treatment-of-focal-chondral-lesions-of-the-knee-a-systematic-review-and-critical-analysis-of-animal-and-clinical-studies
#16
REVIEW
Leonardo Cavinatto, Betina B Hinkel, Ryan E Tomlinson, Sunny Gupta, Jack Farr, Arthur R Bartolozzi
PURPOSE: To summarize currently available data regarding the use of bone marrow aspirate concentrate (BMAC) for the treatment of focal chondral lesions of the knee in experimental animal models and human clinical studies. METHODS: A systematic review searching for the terms "(bone marrow)" AND "(aspirate OR concentrate)" AND "(cartilage OR chondral OR osteochondral)" was performed in the databases PubMed, Cochrane Central Register of Controlled Trials, and Google Scholar regarding the use of BMAC for the treatment of focal chondral lesions of the knee...
March 11, 2019: Arthroscopy: the Journal of Arthroscopic & related Surgery
https://read.qxmd.com/read/30871629/evaluating-in-vivo-efficacy-toxicity-profile-of-teg001-in-humanized-mice-xenografts-against-primary-human-aml-disease-and-healthy-hematopoietic-cells
#17
Inez Johanna, Trudy Straetemans, Sabine Heijhuurs, Tineke Aarts-Riemens, Håkan Norell, Laura Bongiovanni, Alain de Bruin, Zsolt Sebestyen, Jürgen Kuball
BACKGROUND: γ9δ2T cells, which express Vγ9 and Vδ2 chains of the T cell receptor (TCR), mediate cancer immune surveillance by sensing early metabolic changes in malignant leukemic blast and not their healthy hematopoietic stem counterparts via the γ9δ2TCR targeting joined conformational and spatial changes of CD277 at the cell membrane (CD277J). This concept led to the development of next generation CAR-T cells, so-called TEGs: αβT cells Engineered to express a defined γδTCR...
March 12, 2019: Journal for Immunotherapy of Cancer
https://read.qxmd.com/read/30871619/therapeutic-efficacy-pharmacokinetic-profiles-and-toxicological-activities-of-humanized-antibody-drug-conjugate-zt-g4-mmae-targeting-ron-receptor-tyrosine-kinase-for-cancer-therapy
#18
Hang-Ping Yao, Liang Feng, Sreedhar Reddy Suthe, Ling-Hui Chen, Tian-Hao Weng, Chen-Yu Hu, Eun Sung Jun, Zhi-Gang Wu, Wei-Lin Wang, Song Cheol Kim, Xiang-Min Tong, Ming-Hai Wang
BACKGROUND: Aberrant expression of the RON receptor tyrosine kinase is a pathogenic feature and a validated drug target in various types of cancers. Currently, therapeutic antibodies targeting RON for cancer therapy are under intensive evaluation. Here we report the development and validation of a novel humanized anti-RON antibody-drug conjugate for cancer therapy. METHODS: Antibody humanization was achieved by grafting sequences of complementarity-determining regions from mouse monoclonal antibody Zt/g4 into human IgG1/κ acceptor frameworks...
March 14, 2019: Journal for Immunotherapy of Cancer
https://read.qxmd.com/read/30870501/clonal-analyses-of-refractory-testicular-germ-cell-tumors
#19
Michael T Barrett, Elzbieta Lenkiewicz, Smriti Malasi, Melissa Stanton, James Slack, Paul Andrews, Lance Pagliaro, Alan H Bryce
Testicular germ cell tumors (TGCTs) are unique amongst solid tumors in terms of the high cure rates using chemotherapy for metastatic disease. Nevertheless, TGCTs still kill approximately 400 men per year, at a median age of 30 years, in the United States. This young age of mortality dramatically amplifies the impact of these deaths for the patients and their often young families. Furthermore the high cure rate makes it difficult to conduct further clinical trials of non curable disease. TGCTs are characterized by a marked aneuploidy and the presence of gain of chromosomal region 12p...
2019: PloS One
https://read.qxmd.com/read/30869995/effects-and-mechanisms-of-tea-for-the-prevention-and-management-of-cancers-an-updated-review
#20
Xiao-Yu Xu, Cai-Ning Zhao, Shi-Yu Cao, Guo-Yi Tang, Ren-You Gan, Hua-Bin Li
Tea is a traditional and popular beverage worldwide, and the consumption of tea has been demonstrated to possess many health benefits, such as cardiovascular protection, anti-obesity, anti-diabetes, and anticancer. Epidemiological studies have shown that the consumption of tea is inversely associated with the risk of several cancers. In addition, experimental studies have revealed that the anticancer actions of tea are mainly attributed to tea polyphenols, such as epigallocatechin-3-gallate and theaflavins...
March 14, 2019: Critical Reviews in Food Science and Nutrition
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