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    7609 results match your criteria Severe Combined Immunodeficiency

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    Augmented expression of RUNX1 deregulates the global gene expression of U87 glioblastoma multiforme cells and inhibits tumor growth in mice.
    Tumour Biol 2017 Apr;39(4):1010428317698357
    1 The Laboratory of Molecular Genetics, Hepatic-Bili-Pancreatic Cancer Research, Department of Surgery B, Tel Aviv Sourasky Medical Center, The Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
    Glioblastoma multiforme is the most common and aggressive primary brain tumor in adults. A mesenchymal phenotype was associated with tumor aggressiveness and poor prognosis in glioblastoma multiforme patients. Recently, the transcription factor RUNX1 was suggested as a driver of the glioblastoma multiforme mesenchymal gene expression signature; however, its independent role in this process is yet to be described. Read More

    Impact of altered endogenous IgG on unspecific mAb clearance.
    J Pharmacokinet Pharmacodyn 2017 Apr 24. Epub 2017 Apr 24.
    Institute of Mathematics, Universität Potsdam, Karl-Liebknecht-Str. 24-25, 14476, Potsdam, Golm, Germany.
    Immunodeficient mice are crucial models to evaluate the efficacy of monoclonal antibodies (mAbs). When studying mAb pharmacokinetics (PK), protection from elimination by binding to the neonatal Fc receptor (FcRn) is known to be a major process influencing the unspecific clearance of endogenous and therapeutic IgG. The concentration of endogenous IgG in immunodeficient mice, however is reduced, and this effect on the FcRn protection mechanism and subsequently on unspecific mAb clearance is unknown, yet of great importance for the interpretation of mAb PK data. Read More

    Linking newborn severe combined immunodeficiency screening with targeted exome sequencing: A case report.
    J Allergy Clin Immunol Pract 2017 Apr 21. Epub 2017 Apr 21.
    Immunology, Allergy and Rheumatology Section, Baylor College of Medicine, Houston, Texas; Department of Pediatrics, Texas Children's Hospital, Houston, Texas; Baylor College of Medicine, Houston, Texas.

    Cuprous oxide nanoparticle-inhibited melanoma progress by targeting melanoma stem cells.
    Int J Nanomedicine 2017 5;12:2553-2567. Epub 2017 Apr 5.
    Department of Cell Biology, Second Military Medical University.
    Recent studies have shown that metal and metal oxide have a potential function in antitumor therapy. Our previous studies demonstrated that cuprous oxide nanoparticles (CONPs) not only selectively induce apoptosis of tumor cells in vitro but also inhibit the growth and metastasis of melanoma by targeting mitochondria with little hepatic and renal toxicities in mice. As a further study, our current research revealed that CONPs induced apoptosis of human melanoma stem cells (CD271(+/high) cells) in A375 and WM266-4 melanoma cell lines and could significantly suppress the expression of MITF, SOX10 and CD271 involved in the stemness maintenance and tumorigenesis of melanoma stem cells. Read More

    Digoxin Attenuates Murine Experimental Colitis by Downregulating Th17-related Cytokines.
    Inflamm Bowel Dis 2017 May;23(5):728-738
    *First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan; Departments of †Health Science, ‡Infectious Diseases, §Regenerative and infectious Pathology, and ‖Endoscopic and Photodynamic Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan; and ¶Center for Clinical Research, Hamamatsu University School of Medicine, Hamamatsu, Japan.
    Background: Digoxin, a cardiac glycoside used for the treatment of heart failure, was reported to inhibit the retinoid-related orphan receptor gamma t (RORγt) and attenuate the severity of experimental autoimmune encephalomyelitis and arthritis in mice. However, the effects of digoxin in a mice model of inflammatory bowel disease have not been elucidated.

    Methods: Colitis was induced in severe combined immunodeficiency mice by adoptive transfer of CD45RB CD4 T cells. Read More

    Ecto-5'-nucleotidase (CD73) is a biomarker for clear cell renal carcinoma stem-like cells.
    Oncotarget 2017 Mar 29. Epub 2017 Mar 29.
    School of Radiation Medicine and Protection, Medical College of Soochow University, Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions, Suzhou 215123, China.
    Identification of a specific biomarker for cancer stem cells (CSCs) is of potential applications in the development of effective therapeutic strategies for renal cell carcinoma (RCC). In this study, both the RCC cell line 786-O and surgically removed clear cell RCC (ccRCC) tissues were implemented to grew as spheroids in serum-free medium supplemented with mitogens. This subpopulation possessed key characteristics defining CSCs. Read More

    Haematopoietic stem cell transplantation in primary immunodeficiency patients in the Black Sea Region of Turkey.
    Turk J Haematol 2017 Apr 13. Epub 2017 Apr 13.
    Objective: Haematopoietic stem cell transplantation is a promising curative therapy for many combined primary immunodeficiencies and phagocytic disorders.

    Materials And Methods: We retrospectively reviewed paediatric cases that were diagnosed with primary immunodeficiencies and scheduled for haematopoietic stem cell transplantation.

    Results: We identified 22 patients (median age, 6 months; age range, 1 month to 10 years) with various diagnoses who received haematopoietic stem cell transplantation. Read More

    Distribution of FcRn Across Species and Tissues.
    J Histochem Cytochem 2017 Apr 1:22155417705095. Epub 2017 Apr 1.
    Roche Pharmaceutical Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., Basel, Switzerland (SL, BJ, MBO, AH, SK).
    The neonatal Fc receptor (FcRn) is a major histocompatibility complex class I type molecule that binds to, transports, and recycles immunoglobulin G (IgG) and albumin, thereby protecting them from lysosomal degradation. Therefore, besides the knowledge of FcRn affinity, FcRn protein expression is critical in understanding the pharmacokinetic behavior of Fc-containing biotherapeutics such as monoclonal antibodies. The goal of this investigation was to achieve for the first time a comparative assessment of FcRn distribution across a variety of tissues and species. Read More

    ASGCT 20(th) Anniversary Special Issue of Molecular Therapy: Evolving Gene Therapy in Primary Immunodeficiency.
    Mol Ther 2017 Mar 30. Epub 2017 Mar 30.
    Boston Children's Hospital and Dana-Farber Cancer Institute, Harvard Medical School and Harvard Stem Cell Institute, 300 Longwood Avenue, Boston, MA 02115, USA. Electronic address:
    Prior to the first successful bone marrow transplant in 1968, patients born with severe combined immunodeficiency (SCID) invariably died. Today, with a widening availability of newborn screening, major improvements in the application of allogeneic procedures, and the emergence of successful hematopoietic stem and progenitor cell (HSC/P) gene therapy, the majority of these children can be identified and cured. Here, we trace key steps in the development of clinical gene therapy for SCID and other primary immunodeficiencies (PIDs), and review the prospects for adoption of new targets and technologies. Read More

    Use of p53-Silenced Endothelial Progenitor Cells to Treat Ischemia in Diabetic Peripheral Vascular Disease.
    J Am Heart Assoc 2017 Apr 1;6(4). Epub 2017 Apr 1.
    Department of Medicine, The George Washington University, Washington, DC
    Background: Peripheral vascular disease is a major diabetes mellitus-related complication. In this study, we noted that expressions of proapoptotic p53 gene and its downstream cascade gene such as p21 are upregulated in hyperglycemia. Therefore, we investigated whether p53- and p21-silenced endothelial progenitor cells (EPCs) were able to survive in hyperglycemic milieu, and whether transplantation of either p53 knockout (KO) or p21KO or p53- and p21-silenced EPCs could improve collateral vessel formation and blood flow in diabetic vaso-occlusive peripheral vascular disease mouse models. Read More

    Pathology of Aging in NOD scid gamma Female Mice.
    Vet Pathol 2017 Jan 1:300985817698210. Epub 2017 Jan 1.
    1 Laboratory of Comparative Pathology, Memorial Sloan Kettering Cancer Center, The Rockefeller University, Weill Cornell Medicine, New York, NY, USA.
    In the past decade, NOD.Cg- Prkdc(scid) Il2rg(tm1Wjl)/SzJ (NSG, NOD scid gamma) mice have become a model of choice in several areas of biomedical research; however, comprehensive data on their spontaneous age-related pathology are not currently available in the literature. The prevalence of spontaneous morbidity affecting aged NSG female breeders enrolled in a parasitology study was documented with classification of neoplastic and non-neoplastic (inflammatory, metabolic, degenerative) lesions. Read More

    Oncolytic Adenoviruses Armed with Tumor Necrosis Factor Alpha and Interleukin-2 Enable Successful Adoptive Cell Therapy.
    Mol Ther Oncolytics 2017 Mar 31;4:77-86. Epub 2016 Dec 31.
    Cancer Gene Therapy Group, Faculty of Medicine, University of Helsinki, 00290 Helsinki, Finland; TILT Biotherapeutics, Ltd., 00290 Helsinki, Finland; Comprehensive Cancer Center, Helsinki University Hospital, 00290 Helsinki, Finland.
    Adoptive cell therapy holds much promise in the treatment of cancer but results in solid tumors have been modest. The notable exception is tumor-infiltrating lymphocyte (TIL) therapy of melanoma, but this approach only works with high-dose preconditioning chemotherapy and systemic interleukin (IL)-2 postconditioning, both of which are associated with toxicities. To improve and broaden the applicability of adoptive cell transfer, we constructed oncolytic adenoviruses coding for human IL-2 (hIL2), tumor necrosis factor alpha (TNF-α), or both. Read More

    INSPIIRED: Quantification and Visualization Tools for Analyzing Integration Site Distributions.
    Mol Ther Methods Clin Dev 2017 Mar 18;4:17-26. Epub 2016 Dec 18.
    Department of Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104-6076, USA.
    Analysis of sites of newly integrated DNA in cellular genomes is important to several fields, but methods for analyzing and visualizing these datasets are still under development. Here, we describe tools for data analysis and visualization that take as input integration site data from our INSPIIRED pipeline. Paired-end sequencing allows inference of the numbers of transduced cells as well as the distributions of integration sites in target genomes. Read More

    Tanshinone IIA increases protein expression levels of PERK, ATF6, IRE1α, CHOP, caspase‑3 and caspase‑12 in pancreatic cancer BxPC‑3 cell‑derived xenograft tumors.
    Mol Med Rep 2017 May 22;15(5):3259-3263. Epub 2017 Mar 22.
    Tumor Research Center of Integrative Medicine, Changhua Christian Hospital, Changhua 500‑06, Taiwan, R.O.C.
    Tanshinone (Tan)-IIA is a derivative of phenanthrenequinone and the main active ingredient isolated from Salviae miltiorrhizae radix (Danshen). Previous studies have demonstrated that Tan‑IIA increased the protein expressions levels of protein kinase RNA‑like endoplasmic reticulum kinase (PERK), activating transcription factor (ATF) 6, caspase‑12 and CCAAT‑enhancer‑binding protein homologous protein (CHOP), to induce endoplasmic reticulum (ER) stress and apoptosis in human pancreatic cancer BxPC‑3 cells. However, to the best of our knowledge, the effects of Tan‑IIA on pancreatic cancer cells have not been investigated in vivo. Read More

    Therapeutic Drug Monitoring of Continuous Infusion Doripenem in a Pediatric Patient on Continuous Renal Replacement Therapy.
    J Pediatr Pharmacol Ther 2017 Jan-Feb;22(1):69-73
    An 11-year-old African American male with severe combined immunodeficiency variant, non-cystic fibrosis bronchiectasis, pancreatic insufficiency, chronic mycobacterium avium-intracellulare infection, chronic sinusitis, and malnutrition presented with a 1-week history of fevers. He subsequently developed respiratory decompensation and cefepime was discontinued and doripenem was initiated. Doripenem was the carbapenem used due to a national shortage of meropenem. Read More

    Reticular dysgenesis: international survey on clinical presentation, transplantation and outcome.
    Blood 2017 Mar 22. Epub 2017 Mar 22.
    Biotherapy Clinical Investigation Center, Hopital Necker Enfants Malades, Paris, France.
    Reticular Dysgenesis (RD) is a rare congenital disorder defined clinically by the combination of severe combined immunodeficiency (SCID), agranulocytosis and sensorineural deafness. Mutations in the gene encoding Adenylate Kinase 2 (AK2) were identified to cause the disorder. Hematopoietic stem cell transplantation (HSCT) is the only option to cure this otherwise fatal disease. Read More

    Limiting Thymic Precursor Supply Increases the Risk of Lymphoid Malignancy in Murine X-Linked Severe Combined Immunodeficiency.
    Mol Ther Nucleic Acids 2017 Mar 10;6:1-14. Epub 2016 Dec 10.
    Gene Therapy Research Unit, Children's Medical Research Institute, The University of Sydney and The Sydney Children's Hospitals Network, Westmead, NSW 2145, Australia; Discipline of Child and Adolescent Health, The University of Sydney, Westmead, NSW 2145, Australia. Electronic address:
    In early gene therapy trials for SCID-X1, using γ-retroviral vectors, T cell leukemias developed in a subset of patients secondary to insertional proto-oncogene activation. In contrast, we have reported development of T cell leukemias in SCID-X1 mice following lentivirus-mediated gene therapy independent of insertional mutagenesis. A distinguishing feature in our study was that only a proportion of transplanted γc-deficient progenitors were transduced and therefore competent for reconstitution. Read More

    Good Laboratory Practice Preclinical Safety Studies for GSK2696273 (MLV Vector-Based Ex Vivo Gene Therapy for Adenosine Deaminase Deficiency Severe Combined Immunodeficiency) in NSG Mice.
    Hum Gene Ther Clin Dev 2017 Mar;28(1):17-27
    1 Pathogenesis and Therapy of Primary Immunodeficiencies Unit, San Raffaele Telethon Institute for Gene Therapy (SR-TIGET) , IRCCS San Raffaele Scientific Institute, Milan, Italy.
    GSK2696273 (autologous CD34+ cells transduced with retroviral vector that encodes for the human adenosine deaminase [ADA] enzyme) is a gamma-retroviral ex vivo gene therapy of bone marrow-derived CD34+ cells for the treatment of adenosine deaminase deficiency severe combined immunodeficiency (ADA-SCID). ADA-SCID is a severe monogenic disease characterized by immunologic and nonimmunologic symptoms. Bone-marrow transplant from a matched related donor is the treatment of choice, but it is available for only a small proportion of patients. Read More

    Incidence of typically Severe Primary Immunodeficiency Diseases in Consanguineous and Non-consanguineous Populations.
    J Clin Immunol 2017 Apr 16;37(3):295-300. Epub 2017 Mar 16.
    Soroka University Medical Center, 84101, Beer-Sheva, Israel.
    Purpose: Primary immunodeficiency diseases are considered to be rare diseases; however, data on the exact birth incidences of these diseases are sparse. Southern Israel is inhabited by two major populations: a relatively non-consanguineous Jewish population and a highly consanguineous Muslim Bedouin population. We sought to calculate the incidences of typically severe primary immunodeficiency diseases and compare the incidences in these populations. Read More

    [Primary immunodeficiencies in seriously ill children: Report of 3 clinical cases].
    Rev Chil Pediatr 2017 02;88(1):136-141
    Unidad de Paciente Crítico Pediátrico, Clínica Santa María, Santiago, Chile.
    Primary immunodeficiency diseases (PID) are congenital disorders secondary to an impaired immune response. Infections, autoimmune disorders, atopy, and lymphoproliferative syndromes are commonly associated with this disorder.

    Objective: To present and discuss 3 infants diagnosed with PID. Read More

    Treatment of infants identified as having severe combined immunodeficiency by means of newborn screening.
    J Allergy Clin Immunol 2017 Mar;139(3):733-742
    Department of Pediatrics, Division of Allergy, Immunology, and Bone Marrow Transplantation, University of California, San Francisco, Calif.
    Severe combined immunodeficiency (SCID) is characterized by severely impaired T-cell development and is fatal without treatment. Newborn screening (NBS) for SCID permits identification of affected infants before development of opportunistic infections and other complications. Substantial variation exists between treatment centers with regard to pretransplantation care, and transplantation protocols for NBS identified infants with SCID, as well as infants with other T-lymphopenic disorders detected by using NBS. Read More

    New frontiers in the therapy of primary immunodeficiency: From gene addition to gene editing.
    J Allergy Clin Immunol 2017 Mar;139(3):726-732
    Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, Calif.
    The most severe primary immune deficiency diseases (PIDs) have been successfully treated with allogeneic hematopoietic stem cell transplantation for more than 4 decades. However, such transplantations have the best outcomes when there is a well-matched donor available because immune complications, such as graft-versus-host disease, are greater without a matched sibling donor. Gene therapy has been developed as a method to perform autologous transplantations of a patient's own stem cells that are genetically corrected. Read More

    Low-frequency ultrasound radiosensitization and therapy response monitoring of tumors: an in vivo study.
    Conf Proc IEEE Eng Med Biol Soc 2016 Aug;2016:3227-3230
    A new framework has been introduced in this paper for tumor radiosensitization and therapy response monitoring using low-frequency ultrasound. Human fibrosarcoma xenografts grown in severe combined immunodeficiency (SCID) mice (n = 108) were treated using ultrasound-stimulated microbubbles at various concentration and exposed to different doses of radiation. Low-frequency ultrasound radiofrequency (RF) data were acquired from tumors prior to and at different times after treatment. Read More

    Clinical, Laboratory and Molecular Findings of 63 Patients with Severe Combined Immunodeficiency: A Decade´s Experience.
    J Investig Allergol Clin Immunol 2017 Mar 7. Epub 2017 Mar 7.
    Immunology Asthma and Allergy Research Institute (IAARI),Tehran University of Medical Sciences, Tehran, Iran.
    Background:: Severe combined immunodeficiency (SCID) is known as a pediatric emergency disease with life threatening conditions. This is an exclusive report of clinical evaluation, immunological assessment, molecular analysis and outcomes of SCID patients in a tertiary referral center in Iran.

    Methods: During January 2006 and December 2015, in a prospective cohort study, initial screening and advanced immunological tests were carried out on patients suspected of having SCID. Read More

    Gene therapy for primary immune deficiencies: a Canadian perspective.
    Allergy Asthma Clin Immunol 2017 27;13:14. Epub 2017 Feb 27.
    Developmental and Stem Cell Biology, Research Institute, The Hospital for Sick Children, Toronto, ON Canada.
    The use of gene therapy (GT) for the treatment of primary immune deficiencies (PID) including severe combined immune deficiency (SCID) has progressed significantly in the recent years. In particular, long-term studies have shown that adenosine deaminase (ADA) gene delivery into ADA-deficient hematopoietic stem cells that are then transplanted into the patients corrects the abnormal function of the ADA enzyme, which leads to immune reconstitution. In contrast, the outcome was disappointing for patients with X-linked SCID, Wiskott-Aldrich syndrome and chronic granulomatous disease who received GT followed by autologous gene corrected transplantations, as many developed hematological malignancies. Read More

    Dickkopf-related protein 3 negatively regulates the osteogenic differentiation of rat dental follicle cells.
    Mol Med Rep 2017 Apr 3;15(4):1673-1681. Epub 2017 Feb 3.
    Department of Operative Dentistry and Endodontics, Guangdong Provincial Key Laboratory of Stomatology, Guanghua School of Stomatology, Sun Yat‑sen University, Guangzhou, Guangdong 510055, P.R. China.
    The present study aimed to investigate the effect of Dickkopf-related protein 3 (DKK3) on osteogenic differentiation of rat dental follicle cells (DFCs). A PCR array analysis of Wnt pathway activation in DFCs identified genes dysregulated by mineral induction. Among them, DKK3expression levels were decreased, and further experiments were conducted to investigate its role in DFC osteogenesis. Read More

    Interferon alpha treatment stimulates interferon gamma expression in type I NKT cells and enhances their antiviral effect against hepatitis C virus.
    PLoS One 2017 2;12(3):e0172412. Epub 2017 Mar 2.
    Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical & Health Science, Hiroshima University, Hiroshima, Japan.
    Interferon (IFN) inhibits hepatitis C virus (HCV) replication through up-regulation of intrahepatic IFN-stimulated gene expression but also through activation of host immune cells. In the present study, we analyzed the immune cell-mediated antiviral effects of IFN-α using HCV-infected mice. Urokinase-type plasminogen activator (uPA)-severe combined immunodeficiency (SCID) mice with transplanted human hepatocytes were infected with genotype 1b HCV and injected with human peripheral blood mononuclear cells (PBMCs). Read More

    Potential of Cannabidiol for the Treatment of Viral Hepatitis.
    Pharmacognosy Res 2017 Jan-Mar;9(1):116-118
    Department of Basic Medical Sciences, University of the West Indies, Mona, Jamaica.
    Viral hepatitis B (HBV) and hepatitis C (HCV) pose a major health problem globally and if untreated, both viruses lead to severe liver damage resulting in liver cirrhosis and cancer. While HBV has a vaccine, HCV has none at the moment. The risk of drug resistance, combined with the high cost of current therapies, makes it a necessity for cost-effective therapeutics to be discovered and developed. Read More

    Primary immunodeficiency diseases in Northern Iran.
    Allergol Immunopathol (Madr) 2017 May - Jun;45(3):244-250. Epub 2017 Feb 22.
    Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran; Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Boston, MA, USA. Electronic address:
    Introduction: Primary immunodeficiency diseases (PID) are a heterogeneous group of inherited disorders, characterised by recurrent severe infections, autoimmunity and lymphoproliferation. Despite impressive progress in identification of novel PID, there is an unfortunate lack of awareness among physicians in identification of patients with PID, especially in non-capital cities of countries worldwide.

    Result: This study was performed in a single-centre paediatric hospital in Northern Iran during a 21-year period (1994-2015). Read More

    Molecular determinants for STIM1 activation during store-operated Ca2+ entry.
    Curr Mol Med 2017 Feb 19. Epub 2017 Feb 19.
    Center for Translational Cancer Research, Institute of Biosciences and Technology, Texas A&M University System Health Science Center, 2121 W Holcombe Blvd, Houston, TX 77030, United States.
    Background: STIM/ORAI-mediated store-operated Ca2+ entry (SOCE) mediates a myriad of Ca2+-dependent cellular activities in mammals. Genetic defects in STIM1/ORAI1 lead to devastating severe combined immunodeficiency; whereas gain-of-function mutations in STIM1/ORAI1 are intimately associated with tubular aggregate myopathy. At molecular level, a decrease in the Ca2+ concentrations within the lumen of endoplasmic reticulum (ER) initiates multimerization of the STIM1 luminal domain to switch on the STIM1 cytoplasmic domain to engage and gate ORAI channels, thereby leading to the ultimate Ca2+ influx from the extracellular space into the cytosol. Read More

    The distribution of the apparent diffusion coefficient as an indicator of the response to chemotherapeutics in ovarian tumour xenografts.
    Sci Rep 2017 Feb 21;7:42905. Epub 2017 Feb 21.
    Queensland University of Technology (QUT), Brisbane, Queensland (QLD), Australia.
    Diffusion-weighted magnetic resonance imaging (DW-MRI) was used to evaluate the effects of single-agent and combination treatment regimens in a spheroid-based animal model of ovarian cancer. Ovarian tumour xenografts grown in non-obese diabetic/severe-combined-immunodeficiency (NOD/SCID) mice were treated with carboplatin or paclitaxel, or combination carboplatin/paclitaxel chemotherapy regimens. After 4 weeks of treatment, tumours were extracted and underwent DW-MRI, mechanical testing, immunohistochemical and gene expression analyses. Read More

    Long-term outcome of hematopoietic stem cell transplantation for IL2RG/JAK3 SCID: a cohort report.
    Blood 2017 Apr 16;129(15):2198-2201. Epub 2017 Feb 16.
    Pediatric Immunodeficiency Group, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom.
    Hematopoietic stem cell transplantation (HSCT) cures the T-lymphocyte, B-lymphocyte, and natural killer (NK)-cell differentiation defect in interleukin-2 γ-chain receptor (IL2RG)/JAK3 severe combined immunodeficiency (SCID). We evaluated long-term clinical features, longitudinal immunoreconstitution, donor chimerism, and quality of life (QoL) of IL2RG/JAK3 SCID patients >2 years post-HSCT at our center. Clinical data were collated and patients/families answered PedsQL Generic Core Scale v4. Read More

    Cytotoxic T-lymphocyte-associated protein 4-Ig effectively controls immune activation and inflammatory disease in a novel murine model of leaky severe combined immunodeficiency.
    J Allergy Clin Immunol 2017 Feb 7. Epub 2017 Feb 7.
    VIB Center for Brain & Disease Research, Leuven, Belgium; KU Leuven, Department of Microbiology and Immunology, Leuven-University of Leuven, Leuven, Belgium. Electronic address:
    Background: Severe combined immunodeficiency can be caused by loss-of-function mutations in genes involved in the DNA recombination machinery, such as recombination-activating gene 1 (RAG1), RAG2, or DNA cross-link repair 1C (DCLRE1C). Defective DNA recombination causes a developmental block in T and B cells, resulting in high susceptibility to infections. Hypomorphic mutations in the same genes can also give rise to a partial loss of T cells in a spectrum including leaky severe combined immunodeficiency (LS) and Omenn syndrome (OS). Read More

    EpCAM+ Liver Cancer Stem-Like Cells Exhibiting Autocrine Wnt Signaling Potentially Originate in Cirrhotic Patients.
    Stem Cells Transl Med 2017 Mar 18;6(3):807-818. Epub 2017 Jan 18.
    Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi, India.
    Hepatocellular carcinoma (HCC) is believed to originate from cancer stem cells (CSCs). While epithelial cell adhesion molecule (EpCAM) is a marker of normal hepatic stem cells (HSCs), EpCAM+ cells from HCC behave like CSCs. Since HCC mostly develops on a cirrhotic background, we sought to determine whether CSC-like EpCAM+ cells exist in patients with advanced cirrhosis. Read More

    Establishment of a Novel Myelodysplastic Syndrome (MDS) Xenotransplantation Model.
    Clin Lab 2016 Sep;62(9):1651-1659
    Background: Myelodysplastic syndrome (MDS) is a clonal disease of the elderly characterized by chronic cytopenia, dysplasia, and a high risk of progression to acute myeloid leukemia (AML). Up until now, few animal models that fully recapitulate clinical features of this disease have been available.

    Methods: This study aimed to establish a new MDS xenograft model utilizing a human MDS-derived cell line with heterozygous Y641C mutation of EZH2 (SKM-1). Read More

    Usefulness of humanized cDNA-uPA/SCID mice for the study of hepatitis B virus and hepatitis C virus virology.
    J Gen Virol 2017 Jan 28. Epub 2017 Jan 28.
    14Graduate school of Biomedical Science, Hiroshima University.
    Urokinase-type plasminogen activator-severe combined immunodeficiency (uPA/SCID) mice transplanted with human hepatocytes are permissive for hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. However, one of the problems affecting uPA transgenic mice is the expansion of mouse hepatocyte colonies due to homologous recombination of the uPA gene. In this study, we attempted to infect HBV and HCV in humanized cDNA-uPA/SCID mice, a novel uPA transgenic mouse model designed to overcome this disadvantage. Read More

    Mutations in EXTL3 Cause Neuro-immuno-skeletal Dysplasia Syndrome.
    Am J Hum Genet 2017 Feb 26;100(2):281-296. Epub 2017 Jan 26.
    Department of Experimental Immunology, Academic Medical Centre, PO Box 22660, 1100 DD Amsterdam, the Netherlands. Electronic address:
    EXTL3 regulates the biosynthesis of heparan sulfate (HS), important for both skeletal development and hematopoiesis, through the formation of HS proteoglycans (HSPGs). By whole-exome sequencing, we identified homozygous missense mutations c.1382C>T, c. Read More

    Donor bone marrow cells are essential for iNKT cell-mediated Foxp3+ Treg cell expansion in a murine model of transplantation tolerance.
    Eur J Immunol 2017 Apr 21;47(4):734-742. Epub 2017 Mar 21.
    Department of Urology, Tokyo Women's Medical University, Tokyo, Japan.
    Mixed chimerism induction is the most reliable method for establishing transplantation tolerance. We previously described a novel treatment using a suboptimal dose of anti-CD40 ligand (anti-CD40L) and liposomal formulation of a ligand for invariant natural killer T cells administered to sub-lethally irradiated recipient mice after donor bone marrow cell (BMC) transfer. Recipient mice treated with this regimen showed expansion of a Foxp3-positive regulatory T(Treg) cell phenotype, and formation of mixed chimera. Read More

    Novel compound heterozygous mutations in ZAP70 in a Chinese patient with leaky severe combined immunodeficiency disorder.
    Immunogenetics 2017 Apr 26;69(4):199-209. Epub 2017 Jan 26.
    Division of Immunology, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China.
    In humans, the complete lack of tyrosine kinase ZAP70 function results in combined immunodeficiency (CID), with abnormal thymic development and defective T cell receptor (TCR) signaling of peripheral T cells, characterized by the selective absence of CD8(+) T cells. So far, 15 unique ZAP70 mutations have been identified in approximately 20 patients with CID, with variable clinical presentations. Herein, we report the first case from China of novel compound heterozygous mutations in ZAP70 (c. Read More

    Investigation of Genetic Defects in Severe Combined Immunodeficiency Patients from Turkey by Targeted Sequencing.
    Scand J Immunol 2017 Mar;85(3):227-234
    CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.
    Primary immunodeficiencies (PIDs) represent a large group of disorders with an increased susceptibility to infections. Severe combined immunodeficiency (SCID) is the most severe form of primary immunodeficiencies (PIDs) with marked T-cell lymphopenia. Investigation of the genetic aetiology using classical Sanger sequencing is associated with considerable diagnostic delay. Read More

    Pro-inflammatory effect of a traditional Chinese medicine formula with potent anti-cancer activity in vitro impedes tumor inhibitory potential in vivo.
    Mol Clin Oncol 2016 Dec 24;5(6):717-723. Epub 2016 Oct 24.
    Division of Biology and Chemistry, The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences, Guiyang, Guizhou 550008, P.R. China; Department of Biological Sciences, Guiyang Medical University, Guiyang, Guizhou 550025, P.R. China.
    Medicinal formulas are a part of the complex discipline of traditional Chinese medicine that has been used for centuries in China and East Asia. These formulas predominantly consist of the extracts isolated from herbal plants, animal parts and medicinal minerals. The present study aimed to investigate the impact of 150 formulas, used as non-prescription drugs in China, on the treatment of cancer. Read More

    Screening and analysis of breast cancer genes regulated by the human mammary microenvironment in a humanized mouse model.
    Oncol Lett 2016 Dec 24;12(6):5261-5268. Epub 2016 Oct 24.
    Department of Breast Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
    Tumor microenvironments play critical regulatory roles in tumor growth. Although mouse cancer models have contributed to the understanding of human tumor biology, the effectiveness of mouse cancer models is limited by the inability of the models to accurately present humanized tumor microenvironments. Previously, a humanized breast cancer model in severe combined immunodeficiency mice was established, in which human breast cancer tissue was implanted subcutaneously, followed by injection of human breast cancer cells. Read More

    Chronic mucocutaneous candidiasis disease associated with inborn errors of IL-17 immunity.
    Clin Transl Immunology 2016 Dec 2;5(12):e114. Epub 2016 Dec 2.
    Department of Pediatrics, Hiroshima University Graduate School of Biomedical and Health Sciences , Hiroshima, Japan.
    Chronic mucocutaneous candidiasis (CMC) is characterized by recurrent or persistent infections affecting the nails, skin and oral and genital mucosae caused by Candida spp., mainly Candida albicans. CMC is an infectious phenotype in patients with inherited or acquired T-cell deficiency. Read More

    Inhibition of Transient Receptor Potential Channel Mucolipin-1 (TRPML1) by Lysosomal Adenosine Involved in Severe Combined Immunodeficiency Diseases.
    J Biol Chem 2017 Feb 13;292(8):3445-3455. Epub 2017 Jan 13.
    From the Departments of Physiology and Biophysics and
    Impaired adenosine homeostasis has been associated with numerous human diseases. Lysosomes are referred to as the cellular recycling centers that generate adenosine by breaking down nucleic acids or ATP. Recent studies have suggested that lysosomal adenosine overload causes lysosome defects that phenocopy patients with mutations in transient receptor potential channel mucolipin-1 (TRPML1), a lysosomal Ca(2+) channel, suggesting that lysosomal adenosine overload may impair TRPML1 and then lead to subsequent lysosomal dysfunction. Read More

    Mutation c.256_257delAA in RAG1 Gene in Polish Children with Severe Combined Immunodeficiency: Diversity of Clinical Manifestations.
    Arch Immunol Ther Exp (Warsz) 2016 Dec 12;64(Suppl 1):177-183. Epub 2017 Jan 12.
    Department of Clinical Immunology, Institute of Pediatrics, Jagiellonian University Medical College, Wielicka 265, 30-663, Krakow, Poland.
    Mutations in RAG1 gene may result in different types of severe combined immunodeficiencies. In this study, we compare clinical symptoms and laboratory findings in four children with identical mutation in RAG1 gene. All of analyzed patients presented symptoms of severe combined immunodeficiencies associated or not with Omenn syndrome (OS) features. Read More

    Autoinhibition of the Nuclease ARTEMIS Is Mediated by a Physical Interaction between Its Catalytic and C-terminal Domains.
    J Biol Chem 2017 Feb 12;292(8):3351-3365. Epub 2017 Jan 12.
    From the Institute for Transfusion Medicine, University of Ulm and.
    The nuclease ARTEMIS is essential for the development of B and T lymphocytes. It is required for opening DNA hairpins generated during antigen receptor gene assembly from variable (V), diversity (D), and joining (J) subgenic elements (V(D)J recombination). As a member of the non-homologous end-joining pathway, it is also involved in repairing a subset of pathological DNA double strand breaks. Read More

    CRISPR-Cas9 gene repair of hematopoietic stem cells from patients with X-linked chronic granulomatous disease.
    Sci Transl Med 2017 Jan;9(372)
    Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
    Gene repair of CD34(+) hematopoietic stem and progenitor cells (HSPCs) may avoid problems associated with gene therapy, such as vector-related mutagenesis and dysregulated transgene expression. We used CRISPR (clustered regularly interspaced short palindromic repeat)/Cas9 (CRISPR-associated 9) to repair a mutation in the CYBB gene of CD34(+) HSPCs from patients with the immunodeficiency disorder X-linked chronic granulomatous disease (X-CGD). Sequence-confirmed repair of >20% of HSPCs from X-CGD patients restored the function of NADPH (nicotinamide adenine dinucleotide phosphate) oxidase and superoxide radical production in myeloid cells differentiated from these progenitor cells in vitro. Read More

    FOXN1 deficient nude severe combined immunodeficiency.
    Orphanet J Rare Dis 2017 Jan 11;12(1). Epub 2017 Jan 11.
    Developmental Immunology Group, Department of Paediatrics, University of Oxford, Oxford, UK.
    Nude severe combined immunodeficiency is a rare inherited disease caused by autosomal recessive loss-of-function mutations in FOXN1. This gene encodes a transcription factor essential for the development of the thymus, the primary lymphoid organ that supports T-cell development and selection. To date nine cases have been reported presenting with the clinical triad of absent thymus resulting in severe T-cell immunodeficiency, congenital alopecia universalis and nail dystrophy. Read More

    Alterations in the brain adenosine metabolism cause behavioral and neurological impairment in ADA-deficient mice and patients.
    Sci Rep 2017 Jan 11;7:40136. Epub 2017 Jan 11.
    San Raffaele Telethon Institute for Gene Therapy (SR-TIGET), IRCCS San Raffaele Scientific Institute, Milan, Italy.
    Adenosine Deaminase (ADA) deficiency is an autosomal recessive variant of severe combined immunodeficiency (SCID) caused by systemic accumulation of ADA substrates. Neurological and behavioral abnormalities observed in ADA-SCID patients surviving after stem cell transplantation or gene therapy represent an unresolved enigma in the field. We found significant neurological and cognitive alterations in untreated ADA-SCID patients as well as in two groups of patients after short- and long-term enzyme replacement therapy with PEG-ADA. Read More

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