Browsing by Author "The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins"

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    Alterations of type II classical cadherin, cadherin-10 (CDH10), is associated with pancreatic ductal adenocarcinomas
    (2017-05-01) Natini Jinawath; Meng Shin Shiao; Alexis Norris; Kathleen Murphy; Alison P. Klein; Raluca Yonescu; Christine Iacobuzio-Donahue; Alan Meeker; Artit Jinawath; Charles J. Yeo; James R. Eshleman; Ralph H. Hruban; Jonathan R. Brody; Constance A. Griffin; Shuko Harada; Johns Hopkins Medical Institutions; Mahidol University; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins; Thomas Jefferson University; Kennedy Krieger Institute; ProPath
    © 2017 Wiley Periodicals, Inc. Pancreatic ductal adenocarcinoma (PDAC), either sporadic or familial, has a dismal prognosis and finding candidate genes involved in development of the cancer is crucial for the patient care. First, we identified two patients with germline alterations in or adjacent to CDH10 by chromosome studies and sequencing analyses in 41 familial pancreatic cancer (FPC) cases. One patient had a balanced translocation between chromosome 5 and 20. The breakpoint on chromosome band 5p14.2 was ∼810 Kb upstream of CDH10, while that on chromosome arm 20p was in the pericentromeric region which might result in inactivation of one copy of the gene leading to reduced expression of CDH10. This interpretation was supported by loss of heterozygosity (LOH) seen in this region as determined by short tandem repeat analyses. Another patient had a single nucleotide variant in exon 12 (p.Arg688Gln) of CDH10. This amino acid was conserved among vertebrates and the mutation was predicted to have a pathogenic effect on the protein by several prediction algorithms. Next, we analyzed LOH status in the CDH10 region in sporadic PDAC and at least 24% of tumors had evidence of LOH. Immunohistochemical stains with CDH10 antibody showed a different staining pattern between normal pancreatic ducts and PDAC. Taken together, our data supports the notion that CDH10 is involved in sporadic pancreatic carcinogenesis, and might have a role in rare cases of FPC. Further functional studies are needed to elucidate the tumor suppressive role of CDH10 in pancreatic carcinogenesis.
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    Heritability analysis of spherical equivalent, axial length, corneal curvature, and anterior chamber depth in the Beaver Dam Eye Study
    (2009-05-01) Alison P. Klein; Bhoom Suktitipat; Priya Duggal; Kristine E. Lee; Ronald Klein; Joan E. Bailey-Wilson; Barbara E.K. Klein; The Johns Hopkins School of Medicine; Johns Hopkins Bloomberg School of Public Health; National Human Genome Research Institute; Mahidol University; University of Wisconsin School of Medicine and Public Health; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
    Objective: To examine genetic influences for quantitative refraction. Spherical equivalent and its related binary traits of myopia and hyperopia are highly correlated within families. Many linkage regions have been reported for myopia, high myopia, and quantitative refraction. However, the measured phenotype of spherical equivalent is in large part dictated by the relationship between the underlying optical components of axial length, corneal curvature, and anterior chamber depth. Methods: Using data from the fourth visit of the Beaver Dam Eye Study, we conducted familial correlation and heritability analysis of quantitative spherical equivalent, axial length, anterior chamber depth, and corneal curvature using data from 715 individuals in 189 pedigrees. Results: Overall, every trait was highly heritable. Heritability estimates were 0.58 (SE 0.13) for spherical equivalent after adjustment for age, education, and nuclear sclerosis; 0.95 (SE 0.11) for corneal curvature after adjustment for height; 0.67 (SE 0.14) for axial length after adjustment for height and education; and 0.78 (SE 0.14) for anterior chamber depth after adjustment for age, education, height, and nuclear sclerosis. Conclusion: Refraction and the underlying traits of axial length, corneal curvature, and anterior chamber depth are highly heritable. Genetic analysis of these traits may provide greater insight into the development of refractive errors. ©2009 American Medical Association. All rights reserved.
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    Proceedings From the Fourth Haploidentical Stem Cell Transplantation Symposium (HAPLO2016), San Diego, California, December 1, 2016
    (2018-05-01) Monzr M. Al Malki; Richard Jones; Qing Ma; Dean Lee; Yair Reisner; Jeffrey S. Miller; Peter Lang; Suradej Hongeng; Parameswaran Hari; Samuel Strober; Jianhua Yu; Richard Maziarz; Domenico Mavilio; Denis Claude Roy; Chiara Bonini; Richard E. Champlin; Ephraim J. Fuchs; Stefan O. Ciurea; Humanitas University; IRCCS San Raffaele Scientific Institute; Stanford University School of Medicine; Università degli Studi di Milano; University of Minnesota Twin Cities; Universitätsklinikum Tübingen Medizinische Fakultät; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins; Weizmann Institute of Science Israel; Oregon Health and Science University; University of Texas MD Anderson Cancer Center; Mahidol University; Medical College of Wisconsin; Hopital Maisonneuve-Rosemont; City of Hope National Med Center; Ohio State University; Children's Hospital Columbus
    © 2018 The American Society for Blood and Marrow Transplantation The resurgence of haploidentical stem cell transplantation (HaploSCT) over the last decade is one of the most important advances in the field of hematopoietic stem cell transplantation (HSCT). The modified platforms of T cell depletion either ex vivo (CD34 + cell selection, “megadoses” of purified CD34 + cells, or selective depletion of T cells) or newer platforms of in vivo depletion of T cells, with either post-transplantation high-dose cyclophosphamide or intensified immune suppression, have contributed to better outcomes, with survival similar to that in HLA-matched donor transplantation. Further efforts are underway to control viral reactivation using modified T cells, improve immunologic reconstitution, and decrease the relapse rate post-transplantation using donor-derived cellular therapy products, such as genetically modified donor lymphocytes and natural killer cells. Improvements in treatment-related mortality have allowed the extension of haploidentical donor transplants to patients with hemoglobinopathies, such as thalassemia and sickle cell disease, and the possible development of platforms for immunotherapy in solid tumors. Moreover, combining HSCT from a related donor with solid organ transplantation could allow early tapering of immunosuppression in recipients of solid organ transplants and hopefully prevent organ rejection in this setting. This symposium summarizes some of the most important recent advances in HaploSCT and provides a glimpse in the future of fast growing field.