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    Cernunnos deficiency associated with BCG adenitis and autoimmunity: First case from the national Iranian registry and review of the literature.
    Clin Immunol 2017 Jul 17. Epub 2017 Jul 17.
    Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Science, Tehran, Iran. Electronic address:
    Non-homologous end-joining (NHEJ) is a pathway that repairs double-strand breaks (DSB) in DNA and plays a vital role in V(D)J recombination of immunoglobulin genes. Cernunnos is a DNA repair factor that is involved in nonhomologous end-joining (NHEJ) process. Impairment in Cernunnos leads to a genetic disease characterized by neural disorders, immunodeficiency and increased radiosensitivity. Read More

    Enhanced Prophylaxis plus Antiretroviral Therapy for Advanced HIV Infection in Africa.
    N Engl J Med 2017 07;377(3):233-245
    From the University of Zimbabwe Clinical Research Center, Harare, Zimbabwe (J.H., M.B.-D., G.M., K.N.); Joint Clinical Research Center, Kampala (V.M., C.K., P.M.), Mbarara (A.L.), and Fort Portal (S. Kabahenda) - all in Uganda; Medical Research Council Clinical Trials Unit at University College London (A.J.S., S.L.P., A.G., M.J.T., A.S.W., D.M.G.), Wellcome Trust Centre for Clinical Tropical Medicine and Department of Paediatrics, Imperial College (K.M.), and Queen Mary University of London (A.J.P.), London, and the Centre for Health Economics, University of York, York (S.W.) - all in the United Kingdom; the Department of Medicine and Malawi-Liverpool-Wellcome Trust Clinical Research Program, Blantyre, Malawi (J.M., S. Kaunda); and Moi University School of Medicine, Eldoret (A.S., M.K.), and the Kenya Medical Research Institute (KEMRI) Wellcome Trust Research Program, Kilifi (C.A., K.M.) - both in Kenya.
    Background: In sub-Saharan Africa, among patients with advanced human immunodeficiency virus (HIV) infection, the rate of death from infection (including tuberculosis and cryptococcus) shortly after the initiation of antiretroviral therapy (ART) is approximately 10%.

    Methods: In this factorial open-label trial conducted in Uganda, Zimbabwe, Malawi, and Kenya, we enrolled HIV-infected adults and children 5 years of age or older who had not received previous ART and were starting ART with a CD4+ count of fewer than 100 cells per cubic millimeter. They underwent simultaneous randomization to receive enhanced antimicrobial prophylaxis or standard prophylaxis, adjunctive raltegravir or no raltegravir, and supplementary food or no supplementary food. Read More

    Proteomic characterisation reveals active Wnt-signalling by human multipotent stromal cells as a key regulator of beta cell survival and proliferation.
    Diabetologia 2017 Jul 14. Epub 2017 Jul 14.
    Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada.
    Aims/hypothesis: Novel strategies to stimulate the expansion of beta cell mass in situ are warranted for diabetes therapy. The aim of this study was to elucidate the secretome of human bone marrow (BM)-derived multipotent stromal cells (MSCs) with documented islet regenerative paracrine function. We hypothesised that regenerative MSCs will secrete a unique combination of protein factors that augment islet regeneration. Read More

    Short-Term Alcohol Abstinence Improves Antibacterial Defenses of Chronic Alcohol-Consuming Mice against Gut Bacteria-Associated Sepsis Caused by Enterococcus faecalis Oral Infection.
    Am J Pathol 2017 Jul 11. Epub 2017 Jul 11.
    Department of Internal Medicine, The University of Texas Medical Branch, Galveston, Texas. Electronic address:
    The effects of short-term alcohol abstinence on host antibacterial resistance against Enterococcus faecalis oral infection was investigated in chronic alcohol-consuming mice [mice with 0.1 g/day of 20% ethanol consumption for 12 or 16 weeks (CAC-mice)]. These mice were highly susceptible to the infection; however, after 7 days of alcohol abstinence (aaCAC-mice), their antibacterial resistances were completely restored to the normal mouse level. Read More

    Idiopathic T cell lymphopenia identified in New York State Newborn Screening.
    Clin Immunol 2017 Jul 8;183:36-40. Epub 2017 Jul 8.
    Division of Clinical Immunology, Icahn School of Medicine at Mount Sinai, New York, NY, United States. Electronic address:
    Quantification of T-cell receptor excision circles (TRECs) for newborn screening for SCID has advanced the diagnosis of severe combined immune deficiency (SCID). However, it has led to the identification of infants with T cell lymphopenia without known cause. The clinical characteristics, appropriate laboratory monitoring, and outcomes of patients remain unclear. Read More

    Stem Cell Therapy for Fanconi Anemia.
    Adv Exp Med Biol 2017 Jul 8. Epub 2017 Jul 8.
    Oregon Stem Cell Center, Department of Pediatrics, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR, 97239, USA.
    Stem cell therapy is the administration of stem cells to a patient to treat or prevent a disease. Since stem cells possess the long-term self-renewal capacity and provide daughter cells that differentiate into the specialized cells of each tissue, stem cell therapy will theoretically improve the disease condition for the lifetime of the patient. As the most widely used stem cell therapy, bone marrow transplantation is the treatment of choice for many kinds of blood disorders, including anemias, leukemias, lymphomas, and rare immunodeficiency diseases. Read More

    Flow cytometry-based diagnosis of primary immunodeficiency diseases.
    Allergol Int 2017 Jul 3. Epub 2017 Jul 3.
    Department of Pediatrics and Developmental Biology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.
    Primary immunodeficiencies (PIDs) are a heterogeneous group of inherited diseases of the immune system. The definite diagnosis of PID is ascertained by genetic analysis; however, this takes time and is costly. Flow cytometry provides a rapid and highly sensitive tool for diagnosis of PIDs. Read More

    Acute Myeloid Leukemia in a Patient With X-linked Severe Combined Immunodeficiency.
    J Pediatr Hematol Oncol 2017 Jul 3. Epub 2017 Jul 3.
    *Department of Pediatrics, Shinshu University School of Medicine †Department of Laboratory Medicine, Shinshu University Hospital ‡Department of Infection and Host Defense, Graduate School of Medicine, Shinshu University, Matsumoto, Japan.
    Severe combined immunodeficiency (SCID) is a defect in the differentiation and function of T cells. An increased malignancy risk, mainly lymphatic malignancy, has been described in patients with SCID. We report a patient with X-linked SCID who developed acute myeloid leukemia, derived from the recipient with somatic NRAS mutation 4 months after cord blood transplantation (CBT). Read More

    Infusion of Sibling Marrow in a Patient with Purine Nucleoside Phosphorylase Deficiency Leads to Split Mixed Donor Chimerism and Normal Immunity.
    Front Pediatr 2017 19;5:143. Epub 2017 Jun 19.
    Institute of Cellular Medicine, Newcastle University, Newcastle Upon Tyne, United Kingdom.
    Purine nucleoside phosphorylase (PNP) deficiency, a rare autosomal recessive metabolic disease causes combined immunodeficiency and developmental delay, hypotonia, and spasticity. Patients present with recurrent infections associated with T-lymphocytopenia, characteristically presenting later than patients with classical severe combined immunodeficiency (SCID). PNP, with adenosine deaminase (ADA), is part of the purine salvage pathway. Read More

    Inhibition of ERG Activity in Patient-derived Prostate Cancer Xenografts by YK-4-279.
    Anticancer Res 2017 Jul;37(7):3385-3396
    Department of Urology, University of Washington, Seattle, WA, U.S.A.
    Background/aim: The aim of the current study was to determine the effects of the ERG small-molecule inhibitor YK-4-279 on ERG(+) prostate cancer patient-derived xenografts (PDX).

    Materials And Methods: ERG activity was blocked using YK-4-279 in three subcutaneously-implanted ERG(+) (LuCaP 23.1, 86. Read More

    Prevention of Human Lymphoproliferative Tumor Formation in Ovarian Cancer Patient-Derived Xenografts.
    Neoplasia 2017 Jun 25;19(8):628-636. Epub 2017 Jun 25.
    Department of Medical Oncology, Mayo Clinic, Rochester, MN, 55905. Electronic address:
    Interest in preclinical drug development for ovarian cancer has stimulated development of patient-derived xenograft (PDX) or tumorgraft models. However, the unintended formation of human lymphoma in severe combined immunodeficiency (SCID) mice from Epstein-Barr virus (EBV)-infected human lymphocytes can be problematic. In this study, we have characterized ovarian cancer PDXs which developed human lymphomas and explore methods to suppress lymphoproliferative growth. Read More

    A novel PAX1 null homozygous mutation in autosomal recessive otofaciocervical syndrome associated with severe combined immunodeficiency.
    Clin Genet 2017 Jun 28. Epub 2017 Jun 28.
    Department of Experimental and Clinical Biomedical Sciences "Mario Serio", Medical Genetics Unit, University of Florence, Florence, Italy.
    Otofaciocervical syndrome is a rare disorder characterized by facial anomalies, cup-shaped low-set ears, preauricular fistulas, hearing loss, branchial defects, skeletal anomalies, and mild intellectual disability. Autosomal dominant cases are caused by deletions or point mutations of EYA1. A single family with an autosomal recessive form of otofaciocervical syndrome and a homozygous missense mutation in PAX1 gene has been described. Read More

    In Vivo Murine-Matured Human CD3(+) Cells as a Preclinical Model for T Cell-Based Immunotherapies.
    Mol Ther Methods Clin Dev 2017 Sep 17;6:17-30. Epub 2017 May 17.
    Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USA.
    Adoptive cellular immunotherapy is a promising and powerful method for the treatment of a broad range of malignant and infectious diseases. Although the concept of cellular immunotherapy was originally proposed in the 1990s, it has not seen successful clinical application until recent years. Despite significant progress in creating engineered receptors against both malignant and viral epitopes, no efficient preclinical animal models exist for rapidly testing and directly comparing these engineered receptors. Read More

    Calcineurin inhibitors exacerbate coronary arteritis via the MyD88 signalling pathway in a murine model of Kawasaki disease.
    Clin Exp Immunol 2017 Jun 22. Epub 2017 Jun 22.
    Division of Molecular Immunology, Research Center for Infectious Diseases, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
    Calcineurin inhibitors (CNIs) have been used off-label for the treatment of refractory Kawasaki disease (KD). However, it remains unknown whether CNIs show protective effects against the development of coronary artery lesions in KD patients. To investigate the effects of CNIs on coronary arteries and the mechanisms of their actions on coronary arteritis in a mouse model of KD, we performed experiments with FK565, a ligand of nucleotide-binding oligomerization domain-containing protein 1 (NOD1) in wild-type, severe combined immunodeficiency (SCID), caspase-associated recruitment domain 9 (CARD9)(-/-) and myeloid differentiation primary response gene 88 (MyD88)(-/-) mice. Read More

    Absence of γ-chain in keratinocytes alters chemokine secretion resulting in reduced immune cell recruitment.
    J Invest Dermatol 2017 Jun 17. Epub 2017 Jun 17.
    Institute of Immunity and Transplantation, University College London, London, United Kingdom; Department of Immunology, Royal Free Hospital Foundation Trust, London, United Kingdom. Electronic address:
    Loss of function mutations in the common gamma (γc) chain cytokine receptor subunit give rise to severe combined immunodeficiency (SCID) characterised by lack of T and natural killer cells and infant death from infection. Haematopoietic stem cell transplantation or gene therapy offer cure but despite successful replacement of lymphoid immune lineages a long-term risk of severe cutaneous human papilloma virus (HPV) infections persists, possibly related to persistent γc-deficiency in other cell types. Here we demonstrate that keratinocytes, the only cell type directly infected by HPV, express functional γc and its co-receptors. Read More

    Single Cell-Based Vector Tracing in Patients with ADA-SCID Treated with Stem Cell Gene Therapy.
    Mol Ther Methods Clin Dev 2017 Sep 25;6:8-16. Epub 2017 May 25.
    Department of Human Genetics, National Center for Child Health and Development, Tokyo 157-8535, Japan.
    Clinical improvement in stem cell gene therapy (SCGT) for primary immunodeficiencies depends on the engraftment levels of genetically corrected cells, and tracing the transgene in each hematopoietic lineage is therefore extremely important in evaluating the efficacy of SCGT. We established a single cell-based droplet digital PCR (sc-ddPCR) method consisting of the encapsulation of a single cell into each droplet, followed by emulsion PCR with primers and probes specific for the transgene. A fluorescent signal in a droplet indicates the presence of a single cell carrying the target gene in its genome, and this system can clearly determine the ratio of transgene-positive cells in the entire population at the genomic level. Read More

    Targeting PI3K-AKT-mTOR by LY3023414 inhibits human skin squamous cell carcinoma cell growth in vitro and in vivo.
    Biochem Biophys Res Commun 2017 Aug 13;490(2):385-392. Epub 2017 Jun 13.
    Skin & Cosmetic Research Department, Shanghai Skin Disease Hospital, Shanghai, China.
    Abnormal activation of PI3K-AKT-mTOR signaling is detected in human skin squamous cell carcinoma (SCC). LY3023414 is a novel, potent, and orally bio-available PI3K-AKT-mTOR inhibitor. Its activity against human skin SCC cells was tested. Read More

    Looking for the Most Suitable Orthotopic Retinoblastoma Mouse Model in Order to Characterize the Tumoral Development.
    Invest Ophthalmol Vis Sci 2017 Jun;58(7):3055-3064
    Institut Curie, Research Center, PSL Research University, Chemistry, Modelisation and Imaging for Biology (CMIB), Centre Universitaire, Orsay, France 2INSERM U 1196, CNRS UMR 9187, Paris-Saclay University, Paris-Sud University, Centre Universitaire, Orsay, France.
    Purpose: Because retinoblastoma therapies have many adverse effects, new approaches must be developed and evaluated on animal models. We describe orthotopic xenograft models of retinoblastoma using different strains of mice, suitable for this purpose.

    Methods: Human retinoblastoma tumors were established on immunodeficient mice by subcutaneous engraftment of tumors from enucleated eyes. Read More

    Hematopoietic stem cell transplantation in patients with Gain of Function STAT1 Mutation.
    J Allergy Clin Immunol 2017 Jun 7. Epub 2017 Jun 7.
    Department of Pediatrics, University of Washington and Seattle Children's Research Institute, Seattle, Washington, USA. Electronic address:
    Background: Gain of function mutations in signal transducer and activator of transcription 1 (GOF-STAT1) cause a susceptibility to a range of infections, autoimmunity, immune dysregulation, and combined immunodeficiency. Disease manifestations can be mild or severe and life threatening. Hematopoietic stem cell transplantation (HSCT) has been utilized in some patients with more severe symptoms to treat and cure the disorder. Read More

    A novel pathogenic frameshift variant of CD3E gene in two T-B+ NK+ SCID patients from Turkey.
    Immunogenetics 2017 Jun 9. Epub 2017 Jun 9.
    Department of Genetics, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey.
    Severe combined immunodeficiency (SCID) is the most severe form of primary immunodeficiency, which is characterized by the dysfunction and/or absence of T lymphocytes. Early diagnosis of SCID is crucial for overall survival, and if it remains untreated, SCID is often fatal. Next-generation sequencing (NGS) has become a rapid, high-throughput technology, and has already been proven to be beneficial in medical diagnostics. Read More

    Human IκBα Gain of Function: a Severe and Syndromic Immunodeficiency.
    J Clin Immunol 2017 Jul 9;37(5):397-412. Epub 2017 Jun 9.
    St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, USA.
    Germline heterozygous gain-of-function (GOF) mutations of NFKBIA, encoding IκBα, cause an autosomal dominant (AD) form of anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID). Fourteen unrelated patients have been reported since the identification of the first case in 2003. All mutations enhanced the inhibitory activity of IκBα, by preventing its phosphorylation on serine 32 or 36 and its subsequent degradation. Read More

    Multicolor Flow Cytometry for the Diagnosis of Primary Immunodeficiency Diseases.
    J Clin Immunol 2017 Jul 8;37(5):486-495. Epub 2017 Jun 8.
    Department of Pediatrics and Developmental Biology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan.
    Purpose: Primary immunodeficiency diseases (PIDDs) are rare inherited diseases that impair the human immune system. We established a multicolor flow cytometric assay to comprehensively evaluate the immune status and immunological characteristics of patients with PIDDs.

    Methods: Fifty-nine normal controls and 75 patients with PIDDs, including X-linked severe combined immunodeficiency (X-SCID), X-linked agammaglobulinemia (XLA), X-linked hyper IgM syndrome (X-HIGM), ataxia telangiectasia (AT), Wiskott-Aldrich syndrome (WAS), hyper IgE syndrome (HIES), and chronic mucocutaneous candidiasis disease (CMCD), were enrolled in this study. Read More

    Novel RAG1 mutation and the occurrence of mycobacterial and Chromobacterium violaceum infections in a case of leaky SCID.
    Microb Pathog 2017 Aug 25;109:114-119. Epub 2017 May 25.
    Department of Biotechnology and Genetic Engineering, Kohat University of Science and Technology, Kohat, Pakistan.
    Severe combined immunodeficiency (SCID) is a potentially fatal primary immunodeficiency (PID) that is caused by mutations in genes such as IL2RG, JAK3, IL7RA, RAG1, RAG2, and ADA. The products of these genes are involved in the development of several immune cells such as T, B and natural killer (NK) cells. Most of the SCID forms are autosomal recessive with the exception of IL2RG defects that cause an X-linked SCID. Read More

    Recent advances in the study of immunodeficiency and DNA damage response.
    Int J Hematol 2017 May 26. Epub 2017 May 26.
    Department of Pediatrics and Developmental Biology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan.
    DNA breaks can be induced by exogenous stimuli or by endogenous stress, but are also generated during recombination of V, D, and J genes (V(D)J recombination), immunoglobulin class switch recombination (CSR). Among various DNA breaks generated, DNA double strand break (DSB) is the most deleterious one. DNA damage response (DDR) is initiated when DSBs are detected, leading to DNA break repair by non-homologous end joining (NHEJ). Read More

    A Novel PGM3 Mutation Is Associated With a Severe Phenotype of Bone Marrow Failure, Severe Combined Immunodeficiency, Skeletal Dysplasia, and Congenital Malformations.
    J Bone Miner Res 2017 May 22. Epub 2017 May 22.
    Department of Pediatrics, Centre Hospitalier Universitaire Sainte-Justine, Montreal, Canada.
    Congenital disorders of glycosylation (CDGs) affect multiple systems and present a broad spectrum of clinical features, often including skeletal dysplasia. Exome sequencing has led to the identification of new CDG genes. Immune and skeletal phenotypes associated with mutations in PGM3, encoding a protein that converts N-acetyl-glucosamine-6-phosphate into N-acetyl-glucosamine-1-phosphate, were recently reported. Read More

    Development of real-time RT-PCR assays for detection of three classes of HHV-6A gene transcripts.
    J Med Virol 2017 May 23. Epub 2017 May 23.
    Department of Pediatrics, Fujita Health University School of Medicine, Toyoake, Aichi, Japan.
    Human herpesvirus 6 (HHV-6), a member of the betaherpesvirus family, has two distinct species: HHV-6A and HHV-6B. HHV-6B real-time reverse transcription polymerase chain reaction (RT-PCR) has been used to distinguish between active and latent viral infection. In this study, we developed a real-time RT-PCR assay to detect HHV-6A-specific transcripts and evaluated its reliability for analysis of clinical samples. Read More

    Identification of 22q11.2 Deletion Syndrome via Newborn Screening for Severe Combined Immunodeficiency.
    J Clin Immunol 2017 Jul 24;37(5):476-485. Epub 2017 May 24.
    The 22q and You Center, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
    Purpose: Chromosome 22q11.2 deletion syndrome (22q11.2DS), the most common cause of DiGeorge syndrome, is quite variable. Read More

    Haematopoietic stem cell transplantation for severe combined immunodeficiency: Long-term health outcomes and patient perspectives.
    J Paediatr Child Health 2017 May 17. Epub 2017 May 17.
    Department of Immunology and Infectious Diseases, Sydney Children's Hospital, Sydney, New South Wales, Australia.
    Aim: To examine the long-term follow-up and health outcomes of patients who have undergone haematopoietic stem cell transplant (HSCT) for severe combined immunodeficiency (SCID).

    Methods: Through a structured questionnaire, we examined follow-up arrangements and long-term health outcomes in 22 children who have had a successful HSCT for SCID during the period of 1984-2012 at the Sydney Children's Hospital, Sydney, Australia.

    Results: Most children considered themselves healthy and 'cured' from SCID. Read More

    Jak3 deficiency blocks innate lymphoid cell development.
    Mucosal Immunol 2017 May 17. Epub 2017 May 17.
    Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.
    Loss-of-function mutations in the tyrosine kinase JAK3 cause autosomal recessive severe combined immunodeficiency (SCID). Defects in this form of SCID are restricted to the immune system, which led to the development of immunosuppressive JAK inhibitors. We find that the B6. Read More

    Clinical, immunologic, molecular analyses and outcomes of iranian patients with LRBA deficiency: A longitudinal study.
    Pediatr Allergy Immunol 2017 May 17. Epub 2017 May 17.
    Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.
    Background: LPS-responsive beige-like anchor protein (LRBA) deficiency is a combined immunodeficiency caused by mutation in LRBA gene. The patients have a variety of clinical symptoms including hypogammaglobulinemia, recurrent infections, autoimmunity, and enteropathy.

    Methods: A total of 17 LRBA-deficient patients were enrolled in this longitudinal study. Read More

    Intrathymic injection of hematopoietic progenitor cells establishes functional T cell development in a mouse model of severe combined immunodeficiency.
    J Hematol Oncol 2017 May 16;10(1):109. Epub 2017 May 16.
    Department of Pediatrics, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, USA.
    Background: Even though hematopoietic stem cell transplantation can be curative in patients with severe combined immunodeficiency, there is a need for additional strategies boosting T cell immunity in individuals suffering from genetic disorders of lymphoid development. Here we show that image-guided intrathymic injection of hematopoietic stem and progenitor cells in NOD-scid IL2rγ(null) mice is feasible and facilitates the generation of functional T cells conferring protective immunity.

    Methods: Hematopoietic stem and progenitor cells were isolated from the bone marrow of healthy C57BL/6 mice (wild-type, Luciferase(+), CD45. Read More

    Idiopathic collapsing focal segmental glomerulosclerosis in an 81-year-old Japanese woman: a case report and review of the literature.
    CEN Case Rep 2016 Nov 15;5(2):197-202. Epub 2016 Jun 15.
    Department of Nephrology, Yokohama City Minato Red Cross Hospital, 3-12-1 Shinyamashita, Naka-ku, Yokohama, Kanagawa, 231-8682, Japan.
    Focal segmental glomerulosclerosis (FSGS) is classified into five variants, with the collapsing variant being the most rare. Collapsing FSGS is characterized by a black racial predominance and is often associated with human immunodeficiency virus-associated nephropathy. However, the number of idiopathic cases is increasing and the presentation of non-black patients becoming more routine. Read More

    An evaluation of the TREC assay with regard to the integration of SCID screening into the Dutch newborn screening program.
    Clin Immunol 2017 Jul 6;180:106-110. Epub 2017 May 6.
    Centre for Infectious Diseases Research, Diagnostics and Screening, Institute of Public Health and the Environment (RIVM), Bilthoven, The Netherlands. Electronic address:
    Newborn screening of severe combined immunodeficiency through the detection of T-cell receptor excision circles will provide the opportunity of treating before the occurrence of life-threatening infections. With the EnLite Neonatal TREC assay (PerkinElmer) and end-point PCR, 39 samples (3.0%) of 1295 heel prick cards of the Dutch newborn screening program required a retest after initial analysis. Read More

    Oncogenic activity of amplified miniature chromosome maintenance 8 in human malignancies.
    Oncogene 2017 Jun 8;36(25):3629-3639. Epub 2017 May 8.
    Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
    Miniature chromosome maintenance (MCM) proteins play critical roles in DNA replication licensing, initiation and elongation. MCM8, one of the MCM proteins playing a critical role in DNA repairing and recombination, was found to have overexpression and increased DNA copy number in a variety of human malignancies. The gain of MCM8 is associated with aggressive clinical features of several human cancers. Read More

    Genetic Engineering and Manufacturing of Hematopoietic Stem Cells.
    Mol Ther Methods Clin Dev 2017 Jun 18;5:96-105. Epub 2017 Mar 18.
    Cell Therapy and Cell Engineering Facility, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
    The marketing approval of genetically engineered hematopoietic stem cells (HSCs) as the first-line therapy for the treatment of severe combined immunodeficiency due to adenosine deaminase deficiency (ADA-SCID) is a tribute to the substantial progress that has been made regarding HSC engineering in the past decade. Reproducible manufacturing of high-quality, clinical-grade, genetically engineered HSCs is the foundation for broadening the application of this technology. Herein, the current state-of-the-art manufacturing platforms to genetically engineer HSCs as well as the challenges pertaining to production standardization and product characterization are addressed in the context of primary immunodeficiency diseases (PIDs) and other monogenic disorders. Read More

    Recommendations for Screening and Management of Late Effects in Patients with Severe Combined Immunodeficiency after Allogenic Hematopoietic Cell Transplantation: A Consensus Statement from the Second Pediatric Blood and Marrow Transplant Consortium International Conference on Late Effects after Pediatric HCT.
    Biol Blood Marrow Transplant 2017 Aug 4;23(8):1229-1240. Epub 2017 May 4.
    Department of Pediatrics, Allergy, Immunology, and Blood and Marrow Transplant Division, University of California San Francisco, San Francisco California, California.
    Severe combined immunodeficiency (SCID) is effectively treated with hematopoietic cell transplantation (HCT), with overall survival approaching 90% in contemporary reports. However, survivors are at risk for developing late complications because of the variable durability of high-quality immune function, underlying genotype of SCID, comorbidities due to infections in the pretransplantation and post-transplantation periods, and use of conditioning before transplantation. An international group of transplantation experts was convened in 2016 to review the current knowledge of late effects seen in SCID patients after HCT and to develop recommendations for screening and monitoring for late effects. Read More

    Hypoxic preconditioning of myoblasts implanted in a tissue engineering chamber significantly increases local angiogenesis via upregulation of myoblast VEGF-A expression, and downregulation of miRNA-1, miRNA-206 and Angiopoietin 1.
    J Tissue Eng Regen Med 2017 May 6. Epub 2017 May 6.
    O'Brien Institute Department, at St Vincent's Institute, Melbourne, Australia.
    Vascularization is a major hurdle for growing 3 dimensional tissue engineered constructs. This study investigated the mechanisms involved in hypoxic preconditioning of primary rat myoblasts in vitro and their influence on local angiogenesis post-implantation. Primary rat myoblast cultures were exposed to 90 minutes hypoxia at < 1% oxygen followed by normoxia for 24 hours. Read More

    Durable Control of Autoimmune Diabetes in Mice Achieved by Intraperitoneal Transplantation of "Neo-Islets," Three-Dimensional Aggregates of Allogeneic Islet and "Mesenchymal Stem Cells".
    Stem Cells Transl Med 2017 Jul 3;6(7):1631-1643. Epub 2017 May 3.
    SymbioCellTech, LLC, Salt Lake City, Utah, USA.
    Novel interventions that reestablish endogenous insulin secretion and thereby halt progressive end-organ damage and prolong survival of patients with autoimmune Type 1 diabetes mellitus (T1DM) are urgently needed. While this is currently accomplished with allogeneic pancreas or islet transplants, their utility is significantly limited by both the scarcity of organ donors and life-long need for often-toxic antirejection drugs. Coadministering islets with bone marrow-derived mesenchymal stem cells (MSCs) that exert robust immune-modulating, anti-inflammatory, anti-apoptotic, and angiogenic actions, improves intrahepatic islet survival and function. Read More

    CD8 T cells contribute to lacrimal gland pathology in the nonobese diabetic mouse model of Sjögren syndrome.
    Immunol Cell Biol 2017 May 3. Epub 2017 May 3.
    Stead Family Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, IA, USA.
    Sjögren syndrome is an autoimmune disease characterized by targeted destruction of the lacrimal and salivary glands resulting in symptoms of severe ocular and oral dryness. Despite its prevalence, the mechanisms driving autoimmune manifestations are unclear. In patients and in the nonobese diabetic (NOD) mouse model of Sjögren syndrome, lymphocytic infiltrates consist of CD4 and CD8 T cells, although the role of CD8 T cells in disease pathogenesis has been largely unexplored. Read More

    Cooperation of neurotrophin receptor TrkB and Her2 in breast cancer cells facilitates brain metastases.
    Breast Cancer Res 2017 Apr 26;19(1):51. Epub 2017 Apr 26.
    Division of Neurosurgery, Beckman Research Institute, City of Hope, 1500 E. Duarte Rd, Duarte, CA, 91010, USA.
    Background: Patients with primary breast cancer that is positive for human epidermal growth factor receptor 2 (Her2+) have a high risk of developing metastases in the brain. Despite gains with systemic control of Her2+ disease using molecular therapies, brain metastases remain recalcitrant to therapeutic discovery. The clinical predilection of Her2+ breast cancer cells to colonize the brain likely relies on paracrine mechanisms. Read More

    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 Aug 24;44(4):351-374. 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 May;8(19):31977-31992
    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

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