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Gorlin syndrome-induced pluripotent stem cells form medulloblastoma with loss of heterozygosity in PTCH1.
In this study, we generated iPSCs derived from fibroblasts of four patients with Gorlin syndrome (Gln-iPSCs) with heterozygous mutations of the PTCH1 gene. Gln-iPSCs from the four patients developed into medulloblastoma, a manifestation of Gorlin syndrome, in 100% (four out of four), of teratomas after implantation into immunodeficient mice, but none (0/584) of the other iPSC-teratomas did so. One of the medulloblastomas showed loss of heterozygosity in the PTCH1 gene while the benign teratoma, i.e. the non-medulloblastoma portion, did not, indicating a close clinical correlation between tumorigenesis in Gorlin syndrome pa...
Source: Aging - May 20, 2020 Category: Biomedical Science Authors: Ikemoto Y, Miyashita T, Nasu M, Hatsuse H, Kajiwara K, Fujii K, Motojima T, Kokido I, Toyoda M, Umezawa A Tags: Aging (Albany NY) Source Type: research
Gorlin syndrome and desmoplastic medulloblastoma: Report of 3 cases with unfavorable clinical course and novel mutations
We present three cases of genetically confirmed Gorlin syndrome with desmoplastic medulloblastoma (DMB) in whom tumor recurred despite standard therapy. One patient was found to have a novel germline missense PTCH1 mutation. Molecular analysis of recurrent tumor using fluorescent in situ hybridization (FISH) revealed PTEN and/ or PTCH1 loss in 2 patients. Whole exome sequencing (WES) of tumor in one patient revealed loss of heterozygosity of PTCH1 and a mutation of GNAS gene in its non‐coding 3′ ‐untranslated region (UTR) with corresponding decreased protein expression. While one patient died despite high‐dose chem...
Source: Pediatric Blood and Cancer - May 4, 2015 Category: Cancer & Oncology Authors: Sridharan Gururangan, Giles Robinson, David W. Ellison, Gang Wu, Xuelian He, Q. Richard Lu, Roger McLendon, Gerald Grant, Timothy Driscoll, Ronnie Neuberg Tags: Brief Report Source Type: research
GSE104499 Gorlin syndrome-derived induced pluripotent stem cells are hypersensitive to Hedgehog-mediated osteogenic induction
Contributors : Daigo Hasegawa ; Toshifumi AzumaSeries Type : Expression profiling by RT-PCROrganism : Homo sapiensGorlin syndrome is an autosomal dominant inherited syndrome that predisposes a patient to the formation of basal cell carcinomas, odontogenic keratocysts, and skeletal anomalies. Patched-1 (PTCH1) is a Hedgehog (Hh) receptor that acts as a negative regulator of constitutive Hh signaling by preventing the G protein-coupled receptor Smoothened from entering the cilium in the absence of Hh protein binding. We generated iPSCs from four unrelated Gorlin syndrome patients with loss-of-function mutations in PTCH1 usin...
Source: GEO: Gene Expression Omnibus - December 1, 2017 Category: Genetics & Stem Cells Tags: Expression profiling by RT-PCR Homo sapiens Source Type: research
Is a Matched Unrelated Donor Search Needed for All Allogeneic Transplant Candidates?
ConclusionsRace, haplotype frequency and disease status at the time of MUD search influence probability to identify a MUD and receive a transplant. Patients with low likelihood to receive a MUD transplant may proceed to a haploidentical transplant as soon as indicated, as this approach does not appear to compromise transplant outcomes.DisclosuresKonopleva: Stemline Therapeutics: Research Funding. Oran: AROG pharmaceuticals: Research Funding; Celgene: Consultancy, Research Funding; ASTEX: Research Funding. Champlin: Otsuka: Research Funding; Sanofi: Research Funding.
Source: Blood - November 21, 2018 Category: Hematology Authors: Ciurea, S. O., Borges Bittencourt, M. C., Milton, D. R., Cao, K., Kongtim, P., Rondon, G., Chen, J., Konopleva, M. Y., Ramos Perez, J. M., Elshazly, M., Aljadayeh, M., Alvarez, M., Im, J. S., Alatrash, G., Mehta, R. S., Popat, U., Bashir, Q., Oran, B., Ho Tags: 732. Clinical Allogeneic Transplantation: Results: Poster II Source Type: research
Outcome of patients activating an unrelated donor search for severe acquired aplastic anemia
This study analyzes the outcome of ATG‐refractory SAA patients activating a VUD search. Of 179 patients, 68 had at least one HLA‐A, –B and –DR matched donor identified and underwent HSCT while 50 also with a donor were not transplanted because of early death (8), late response to IST (34), transplant refusal (1) or other (7). Conversely, 61 had no matched donor, 13 of those ultimately received a mismatched HSCT. All but one received marrow stem cells. Among patients aged <17 years, those with at least one matched donor had a significant higher 4‐year survival as compared to others (79%+/‐6% versus 53%+/‐10...
Source: American Journal of Hematology - June 27, 2013 Category: Hematology Authors: Sébastien Maury, Marie‐Lorraine Balère‐Appert, Simona Pollichieni, Rosi Oneto, Ibrahim Yakoub‐Agha, Franco Locatelli, Jean‐Hugues Dalle, Edoardo Lanino, Alain Fischer, Andrea Pession, Anne Huynh, Walter Barberi, Mohamad Mohty, Antonio Risitano, Tags: Research Article Source Type: research
Influence of the HLA characteristics of Italian patients on donor search outcome in unrelated hematopoietic stem cell transplantation
In this study, we retrospectively analyzed 315 Italian patients who started a search for a MUD, in order to assess the distribution of human leukocyte antigen (HLA) alleles and haplotypes in this population of patients and to evaluate the probability of finding a donor. Comparing two groups of patients based on whether or not a 10/10 HLA‐matched donor was available, we found that patients who had a fully‐matched MUD possessed at least one frequent haplotype more often than the others (45.6% vs 14.3%; P = 0.000003). In addition, analysis of data pertaining to the HLA class I alleles distribution showed that, in the ...
Source: Tissue Antigens - April 18, 2014 Category: Allergy & Immunology Authors: M. Testi, M. Andreani, F. Locatelli, W. Arcese, M. Troiano, M. Battarra, J. Gaziev, G. Lucarelli Tags: Original article Source Type: research
Close to the bone — in search of the skeletal stem cell
Close to the bone — in search of the skeletal stem cell, Published online: 13 November 2018; doi:10.1038/s41584-018-0121-6The search for the identity of skeletal stem cells has reached a point at which skeletogenic cell populations with self-renewing capacity can be enriched and studied in detail. These advances provide new hope for skeletal regenerative medicine.
Source: Nature Reviews Rheumatology - November 13, 2018 Category: Rheumatology Authors: Frank P. Luyten Scott J. Roberts Source Type: research
In Search of Genes that Were Lost in Longer-Lived Mammals
In conclusion, the developed method and its software allowed us to identify a short list of presumably lost genes associated with a long lifespan in Euarchontoglires. The predicted lost genes largely demonstrate specific expressions in reproductive organs, which agrees with Williams' hypothesis concerning the reallocation of the physiological resources of the body between self-maintenance and reproduction (transition from r-strategy to К-strategy in the species evolution). The loss of some predicted vomeronasal and olfactory receptor genes in human and naked mole-rat conforms to their specific anatomical features. We sugg...
Source: Fight Aging! - November 26, 2019 Category: Research Authors: Reason Tags: Daily News Source Type: blogs
Outcomes of strategic alternative donor selection or suspending donor search based on Japan Marrow Donor Program coordination status.
Abstract
In allogeneic hematopoietic stem cell transplantation (allo-HSCT) from unrelated donors, delays in donor search are adversely associated with patient outcome. However, the optimal duration for either waiting for an unrelated donor or selecting alternative sources remains undetermined. Using data from the Japan Marrow Donor Program (JMDP) registry, we retrospectively analyzed 349 adult patients who had searched for unrelated donors. Two hundred and three patients received allo-HSCT from JMDP donors (Group A) with a median of 140 days required to identify a donor, 60 received allo-HSCT from alternative sou...
Source: International Journal of Hematology - January 27, 2018 Category: Hematology Authors: Kawashima N, Nishiwaki S, Shimizu N, Kamoshita S, Watakabe K, Yokohata E, Kurahashi S, Ozawa Y, Miyamura K Tags: Int J Hematol Source Type: research
Molecules, Vol. 23, Pages 567: Identification and Characterizations of Novel, Selective Histone Methyltransferase SET7 Inhibitors by Scaffold Hopping- and 2D-Molecular Fingerprint-Based Similarity Search
heng Luo
Kai Chen
SET7, serving as the only histone methyltransferase that monomethylates ‘Lys-4’ of histone H3, has been proved to function as a key regulator in diverse biological processes, such as cell proliferation, transcriptional network regulation in embryonic stem cell, cell cycle control, protein stability, heart morphogenesis and development. What′s more, SET7 is involved inthe pathogenesis of alopecia aerate, breast cancer, tumor and cancer progression, atherosclerosis in human carotid plaques, chronic renal diseases, diabetes, obesity, ovarian cancer, prostate cancer, hepatocellular carcinoma, and ...
Source: Molecules - March 2, 2018 Category: Chemistry Authors: Hong Ding Wen Lu Jun Hu Yu-Chih Liu Chen Zhang Fu Lian Nai Zhang Fan Meng Cheng Luo Kai Chen Tags: Article Source Type: research
Improved accuracy of clinical HLA genotyping by next-generation DNA sequencing affects unrelated donor search results for hematopoietic stem cell transplantation.
Abstract
Matching of human leukocyte antigen (HLA) genes is critically important in hematopoietic stem cell transplantation (HSCT). HLA genes are highly polymorphic and HLA matching has historically been limited by technologies that are unable to unambiguously determine HLA genotypes. Next generation DNA sequencing (NGS) overcomes these limitations by enabling near full-gene sequences with phase determination for heterozygous alleles. Here we examine the efficacy and utility of HLA-NGS in the clinical setting. In a 54-sample validation study and 955 patient samples subsequently tested using HLA-NGS, we observed si...
Source: Human Immunology - October 11, 2018 Category: Allergy & Immunology Authors: Allen ES, Yang B, Garrett J, Ball ED, Maiers M, Morris GP Tags: Hum Immunol Source Type: research
Glycan Markers of Human Stem Cells Assigned with Beam Search Arrays.
Abstract
Glycan antigens recognized by monoclonal antibodies have served as stem cell markers. To understand regulation of their biosynthesis and their roles in stem cell behavior precise assignments are required. We have applied state-of-the-art glycan array technologies to compare the glycans bound by five antibodies that recognize carbohydrates on human stem cells. These are: FC10.2, TRA-1-60, TRA-1-81, anti-i and R-10G. Microarray analyses with a panel of sequence-defined glycans corroborate that FC10.2, TRA-1-60, TRA-1-81 recognize the type 1-(Galβ-3GlcNAc)-terminating backbone sequence, Galβ-3GlcNAcβ-3Gal...
Source: Molecular and Cellular Proteomics : MCP - July 14, 2019 Category: Molecular Biology Authors: Wu N, Silva LM, Liu Y, Zhang Y, Gao C, Zhang F, Fu L, Peng Y, Linhardt R, Kawasaki T, Mulloy B, Chai W, Feizi T Tags: Mol Cell Proteomics Source Type: research
GSE192644 Studying heterogeneity in embryonic stem cells using the approach of search-engine
Contributors : Kedar N Natrajan ; Vibhor KumarSeries Type : Genome binding/occupancy profiling by high throughput sequencingOrganism : Mus musculusHere we designed a search-engine for single-cell epigenome profiles. We tested different application of search-engine using different data-sets including mESC scATAC-seq profile.
Source: GEO: Gene Expression Omnibus - December 27, 2022 Category: Genetics & Stem Cells Tags: Genome binding/occupancy profiling by high throughput sequencing Mus musculus Source Type: research
In search of the pivot point of mechanotransduction: Mechanosensing of stem cells.
This article mainly focuses on the mechanosensing, which is the upstream event of stem cell mechanotransduction and the downstream one of physical stimuli. Putative mechanosensors such as ion channels, integrins, cell membrane, as well as primary cilia are discussed. Since mechanical environment is an important stem cell niche, identification of mechanosensors can not only elucidate the mechanisms of mechanotransduction and fate commitments, but also bring new prospects of the mechanical control as well as drug development for clinical application.
PMID: 23294564 [PubMed - as supplied by publisher]
Source: Cell Transplantation - January 2, 2013 Category: Cytology Authors: Liu YS, Lee OK Tags: Cell Transplant Source Type: research
In situ Search for Breast Cancer Stem Cells and Their Niche: The Film Sheet Epoxy Resin Embedding Method and Breast Cancer Stem Cells.
PMID: 23832410 [PubMed - in process]
Source: Journal of Nippon Medical School - July 11, 2013 Category: Universities & Medical Training Authors: Yamamoto Y, Oguro T, Mieda J, Ohashi R, Tsuchiya S Tags: J Nippon Med Sch Source Type: research
