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6 results on '"George Sandusky"'

1. Loss of Dnmt3a impairs hematopoietic homeostasis and myeloid cell skewing via the PI3Kinase pathway

Author

Lakshmi Reddy Palam, Baskar Ramdas, Katelyn Pickerell, Santhosh Kumar Pasupuleti, Rahul Kanumuri, Annamaria Cesarano, Megan Szymanski, Bryce Selman, Utpal P. Dave, George Sandusky, Fabiana Perna, Sophie Paczesny, and Reuben Kapur

Subjects
Hematology, Medicine
Abstract

Loss-of-function mutations in the DNA methyltransferase 3A (DNMT3A) are seen in a large number of patients with acute myeloid leukemia (AML) with normal cytogenetics and are frequently associated with poor prognosis. DNMT3A mutations are an early preleukemic event, which — when combined with other genetic lesions — result in full-blown leukemia. Here, we show that loss of Dnmt3a in hematopoietic stem and progenitor cells (HSC/Ps) results in myeloproliferation, which is associated with hyperactivation of the phosphatidylinositol 3-kinase (PI3K) pathway. PI3Kα/β or the PI3Kα/δ inhibitor treatment partially corrects myeloproliferation, although the partial rescue is more efficient in response to the PI3Kα/β inhibitor treatment. In vivo RNA-Seq analysis on drug-treated Dnmt3a–/– HSC/Ps showed a reduction in the expression of genes associated with chemokines, inflammation, cell attachment, and extracellular matrix compared with controls. Remarkably, drug-treated leukemic mice showed a reversal in the enhanced fetal liver HSC-like gene signature observed in vehicle-treated Dnmt3a–/– LSK cells as well as a reduction in the expression of genes involved in regulating actin cytoskeleton-based functions, including the RHO/RAC GTPases. In a human PDX model bearing DNMT3A mutant AML, PI3Kα/β inhibitor treatment prolonged their survival and rescued the leukemic burden. Our results identify a potentially new target for treating DNMT3A mutation–driven myeloid malignancies.

Published
2023
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2. Integrated Molecular Characterization of Testicular Germ Cell Tumors

Author

Hui Shen, Juliann Shih, Daniel P. Hollern, Linghua Wang, Reanne Bowlby, Satish K. Tickoo, Vésteinn Thorsson, Andrew J. Mungall, Yulia Newton, Apurva M. Hegde, Joshua Armenia, Francisco Sánchez-Vega, John Pluta, Louise C. Pyle, Rohit Mehra, Victor E. Reuter, Guilherme Godoy, Jeffrey Jones, Carl S. Shelley, Darren R. Feldman, Daniel O. Vidal, Davor Lessel, Tomislav Kulis, Flavio M. Cárcano, Kristen M. Leraas, Tara M. Lichtenberg, Denise Brooks, Andrew D. Cherniack, Juok Cho, David I. Heiman, Katayoon Kasaian, Minwei Liu, Michael S. Noble, Liu Xi, Hailei Zhang, Wanding Zhou, Jean C. ZenKlusen, Carolyn M. Hutter, Ina Felau, Jiashan Zhang, Nikolaus Schultz, Gad Getz, Matthew Meyerson, Joshua M. Stuart, Rehan Akbani, David A. Wheeler, Peter W. Laird, Katherine L. Nathanson, Victoria K. Cortessis, Katherine A. Hoadley, David Wheeler, Daniel Hughes, Kyle Covington, Joy C. Jayaseelan, Viktoriya Korchina, Lora Lewis, Jianhong Hu, HarshaVardhan Doddapaneni, Donna Muzny, Richard Gibbs, Daniel Hollern, Benjamin G. Vincent, Shengjie Chai, Christof C. Smith, J. Todd Auman, Yan Shi, Shaowu Meng, Tara Skelly, Donghui Tan, Umadevi Veluvolu, Piotr A. Mieczkowski, Corbin D. Jones, Matthew D. Wilkerson, Saianand Balu, Tom Bodenheimer, Alan P. Hoyle, Stuart R. Jefferys, Lisle E. Mose, Janae V. Simons, Matthew G. Soloway, Jeffrey Roach, Joel S. Parker, D. Neil Hayes, Charles M. Perou, Gordon Saksena, Carrie Cibulskis, Steven E. Schumacher, Rameen Beroukhim, Stacey B. Gabriel, Adrian Ally, Miruna Balasundaram, Rebecca Carlsen, Dorothy Cheung, Eric Chuah, Noreen Dhalla, Robert A. Holt, Steven J.M. Jones, Yussanne Ma, Michael Mayo, Richard A. Moore, A. Gordon Robertson, Jacqueline E. Schein, Payal Sipahimalani, Angela Tam, Nina Thiessen, Tina Wong, Marco A. Marra, Daniel J. Weisenberger, David J. Van Den Berg, Phillip H. Lai, Mario Berrios, Andrea Holbrook, Moiz S. Bootwalla, Dennis T. Maglinte, Debyani Chakravarty, Jianjiong Gao, Zachary Heins, Ritika Kundra, Angelica Ochoa, Chris Sander, Marc Ladanyi, Vesteinn Thorsson, Amie J. Radenbaugh, Nils Gehlenborg, Doug Voet, Pei Lin, Scott Frazer, Jaegil Kim, Michael S. Lawrence, Sam Meier, Timothy Defreitas, Lynda Chin, John N. Weinstein, Wenbin Liu, Gordon B. Mills, Yiling Lu, Leendert Looijenga, Alan H. Bryce, André L. Carvalho, Darren Feldman, Michael Ittmann, Seth Lerner, Jay Bowen, Julie M. Gastier-Foster, Mark Gerken, Carmen Helsel, Nilsa C. Ramirez, Lisa Wise, Erik Zmuda, Sandra Cottingham, David Chesla, Charles Saller, Katherine Tarvin, Luiz Fernando Lopes, Cristovam Scapulatempo-Neto, Natália D.A. Aredes, Wolter Oosterhuis, Ad Gillis, Hans Stoop, Wil Eijkenboom, George Sandusky, Sue Ellen Martin, Manju Aron, Siamak Daneshmand, Hooman Djaladat, David Quinn, Tanya Dorff, Jochen K. Lennerz, Leigh B. Thorne, Marija Gamulin, Zeljko Kastelan, Tvrtko Hudolin, Christian Kubisch, Lori Boice, Mei Huang, Amy H. Perou, W. Kimryn Rathmell, Todd Pihl, Yunhu Wan, Qiang Sun, Rashi Naresh, Sudha Chudamani, Jia Liu, Laxmi Lolla, Ye Wu, Martin L. Ferguson, Jean C. Zenklusen, Jiashan (Julia) Zhang, Margi Sheth, John A. Demchok, Liming Yang, Zhining Wang, Roy Tarnuzzer, Heidi J. Sofia, and Tanja M. Davidsen

Subjects
0301 basic medicine, Male, endocrine system, DNA Copy Number Variations, endocrine system diseases, Somatic cell, carcinoma in-situ, high-resolution, kit gene, cancer, seminoma, genome, adolescents, expression, mutations, serum, Biology, medicine.disease_cause, urologic and male genital diseases, General Biochemistry, Genetics and Molecular Biology, Article, Embryonal carcinoma, 03 medical and health sciences, 0302 clinical medicine, Germline mutation, Testicular Neoplasms, medicine, Humans, lcsh:QH301-705.5, Epigenomics, Seminoma, DNA Methylation, Neoplasms, Germ Cell and Embryonal, medicine.disease, 3. Good health, Gene Expression Regulation, Neoplastic, MicroRNAs, Proto-Oncogene Proteins c-kit, 030104 developmental biology, lcsh:Biology (General), 030220 oncology & carcinogenesis, DNA methylation, Cancer research, ras Proteins, Teratoma, KRAS
Abstract

SUMMARY We studied 137 primary testicular germ cell tumors (TGCTs) using high-dimensional assays of genomic, epigenomic, transcriptomic, and proteomic features. These tumors exhibited high aneuploidy and a paucity of somatic mutations. Somatic mutation of only three genes achieved significance—KIT, KRAS, and NRAS—exclusively in samples with seminoma components. Integrated analyses identified distinct molecular patterns that characterized the major recognized histologic subtypes of TGCT: seminoma, embryonal carcinoma, yolk sac tumor, and teratoma. Striking differences in global DNA methylation and microRNA expression between histology subtypes highlight a likely role of epigenomic processes in determining histologic fates in TGCTs. We also identified a subset of pure seminomas defined by KIT mutations, increased immune infiltration, globally demethylated DNA, and decreased KRAS copy number. We report potential biomarkers for risk stratification, such as miRNA specifically expressed in teratoma, and others with molecular diagnostic potential, such as CpH (CpA/CpC/CpT) methylation identifying embryonal carcinomas., In Brief Shen et al. identify molecular characteristics that classify testicular germ cell tumor types, including a separate subset of seminomas defined by KIT mutations. This provides a set of candidate biomarkers for risk stratification and potential therapeutic targeting.

Published
2018

3. Comprehensive molecular characterization of muscle invasive bladder cancer

Author

A. Gordon Robertson, Jaegil Kim, Hikmat Al-Ahmadie, Joaquim Bellmunt, Guangwu Guo, Andrew D. Cherniack, Toshinori Hinoue, Peter W. Laird, Katherine A. Hoadley, Rehan Akbani, Mauro A.A. Castro, Ewan A. Gibb, Rupa S. Kanchi, Dmitry A. Gordenin, Sachet A. Shukla, Francisco Sanchez-Vega, Donna E. Hansel, Bogdan A. Czerniak, Victor E. Reuter, Xiaoping Su, Benilton de Sa Carvalho, Vinicius S. Chagas, Karen L. Mungall, Sara Sadeghi, Chandra Sekhar Pedamallu, Yiling Lu, Leszek J. Klimczak, Jiexin Zhang, Caleb Choo, Akinyemi I. Ojesina, Susan Bullman, Kristen M. Leraas, Tara M. Lichtenberg, Catherine J. Wu, Nicholaus Schultz, Gad Getz, Matthew Meyerson, Gordon B. Mills, David J. McConkey, John N. Weinstein, David J. Kwiatkowski, Seth P. Lerner, Monique Albert, Iakovina Alexopoulou, Adrian Ally, Tatjana Antic, Manju Aron, Miruna Balasundaram, John Bartlett, Stephen B. Baylin, Allison Beaver, Inanc Birol, Lori Boice, Moiz S. Bootwalla, Jay Bowen, Reanne Bowlby, Denise Brooks, Bradley M. Broom, Wiam Bshara, Eric Burks, Flavio M. Cárcano, Rebecca Carlsen, Benilton S. Carvalho, Andre L. Carvalho, Eric P. Castle, Patricia Castro, James W. Catto, David W. Chesla, Eric Chuah, Sudha Chudamani, Victoria K. Cortessis, Sandra L. Cottingham, Daniel Crain, Erin Curley, Siamak Daneshmand, John A. Demchok, Noreen Dhalla, Hooman Djaladat, John Eckman, Sophie C. Egea, Jay Engel, Ina Felau, Martin L. Ferguson, Johanna Gardner, Julie M. Gastier-Foster, Mark Gerken, Carmen R. Gomez-Fernandez, Jodi Harr, Arndt Hartmann, Lynn M. Herbert, Thai H. Ho, Robert A. Holt, Carolyn M. Hutter, Steven J.M. Jones, Merce Jorda, Richard J. Kahnoski, Katayoon Kasaian, Phillip H. Lai, Brian R. Lane, Jia Liu, Laxmi Lolla, Yair Lotan, Fabiano R. Lucchesi, Yussanne Ma, Roberto D. Machado, Dennis T. Maglinte, David Mallery, Marco A. Marra, Sue E. Martin, Michael Mayo, Anoop Meraney, Alireza Moinzadeh, Richard A. Moore, Edna M. Mora Pinero, Scott Morris, Carl Morrison, Andrew J. Mungall, Jerome B. Myers, Rashi Naresh, Peter H. O'Donnell, Dipen J. Parekh, Jeremy Parfitt, Joseph D. Paulauskis, Robert J. Penny, Todd Pihl, Sima Porten, Mario E. Quintero-Aguilo, Nilsa C. Ramirez, W. Kimryn Rathmell, Kimberly Rieger-Christ, Charles Saller, Andrew Salner, George Sandusky, Cristovam Scapulatempo-Neto, Jacqueline E. Schein, Anne K. Schuckman, Nikolaus Schultz, Candace Shelton, Troy Shelton, Jeff Simko, Parminder Singh, Payal Sipahimalani, Norm D. Smith, Heidi J. Sofia, Andrea Sorcini, Melissa L. Stanton, Gary D. Steinberg, Robert Stoehr, Travis Sullivan, Qiang Sun, Angela Tam, Roy Tarnuzzer, Katherine Tarvin, Helge Taubert, Nina Thiessen, Leigh Thorne, Kane Tse, Kelinda Tucker, David J. Van Den Berg, Kim E. van Kessel, Sven Wach, Yunhu Wan, Zhining Wang, Daniel J. Weisenberger, Lisa Wise, Tina Wong, Ye Wu, Liming Yang, Leigh Anne Zach, Jean C. Zenklusen, Jiashan (Julia) Zhang, Erik Zmuda, and Ellen C. Zwarthoff

Subjects
0301 basic medicine, Urinary Bladder, Biology, medicine.disease_cause, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, 0302 clinical medicine, microRNA, medicine, Carcinoma, Cluster Analysis, Humans, Neoplasm Invasiveness, Gene, Survival analysis, Aged, Mutation, Bladder cancer, Urinary bladder, Muscle, Smooth, DNA Methylation, Middle Aged, medicine.disease, Survival Analysis, MicroRNAs, 030104 developmental biology, medicine.anatomical_structure, Urinary Bladder Neoplasms, 030220 oncology & carcinogenesis, DNA methylation, Cancer research, RNA, Long Noncoding
Abstract

We report a comprehensive analysis of 412 muscle-invasive bladder cancers characterized by multiple TCGA analytical platforms. Fifty-eight genes were significantly mutated, and the overall mutational load was associated with APOBEC-signature mutagenesis. Clustering by mutation signature identified a high-mutation subset with 75% 5-year survival. mRNA expression clustering refined prior clustering analyses and identified a poor-survival "neuronal" subtype in which the majority of tumors lacked small cell or neuroendocrine histology. Clustering by mRNA, long non-coding RNA (lncRNA), and miRNA expression converged to identify subsets with differential epithelial-mesenchymal transition status, carcinoma in situ scores, histologic features, and survival. Our analyses identified 5 expression subtypes that may stratify response to different treatments.

Published
2017

4. Expression of cyclic adenosine monophosphate response-element binding protein in acute leukemia

Author

George Sandusky, Kathleen M. Sakamoto, Elliot M. Landaw, Theodore B Moore, Smita Bhatia, and Heather N. Crans-Vargas

Subjects
Adult, Adolescent, p300-CBP coactivator family, Blotting, Western, Immunology, Bone Marrow Cells, Leukemia inhibitory factor receptor, Biology, Biochemistry, Promyelocytic leukemia protein, Reference Values, hemic and lymphatic diseases, Acute lymphocytic leukemia, medicine, Humans, CD135, Child, Cyclic AMP Response Element-Binding Protein, Aged, Aged, 80 and over, Acute leukemia, Infant, Myeloid leukemia, Cell Biology, Hematology, Middle Aged, Precursor Cell Lymphoblastic Leukemia-Lymphoma, medicine.disease, Immunohistochemistry, Leukemia, Myeloid, Acute, Leukemia, Child, Preschool, Cancer research, biology.protein
Abstract

Cyclic adenosine monophosphate response-element binding protein (CREB) is a nuclear protein that regulates expression of genes that control cell proliferation, differentiation, and survival. To analyze CREB expression in leukemia cells, we conducted Western blot analysis of bone marrow cells obtained from patients with acute lymphoblastic leukemia, patients with acute myeloid leukemia, and patients without active leukemia. CREB was expressed at a higher frequency in bone marrow cells from patients with acute lymphoid or myeloid leukemia than in patients with leukemia remission or without leukemia. Our results indicate that CREB expression could be a useful marker for leukemia in patients with acute disease and suggest a role for CREB in leukemogenesis.

Published
2002

5. Congenital cardiac anomalies in calves

Author

C. W. Smith and George Sandusky

Subjects
Heart Defects, Congenital, Heart Septal Defects, Ventricular, Male, congenital, hereditary, and neonatal diseases and abnormalities, medicine.medical_specialty, Coronary Vessel Anomalies, Cattle Diseases, Sudden death, Ductus arteriosus, Internal medicine, medicine.artery, medicine, Animals, cardiovascular diseases, Diagnostic laboratory, Ductus Arteriosus, Patent, Heart septal defect, Aorta, Persistent Truncus Arteriosus, General Veterinary, business.industry, General Medicine, medicine.disease, Surgery, medicine.anatomical_structure, Pulmonary artery, cardiovascular system, Cardiac defects, Cardiology, Cattle, Female, business
Abstract

Seven cases of congenital cardiac anomalies in calves were reviewed from the files of the Ohio Veterinary Diagnostic Laboratory. The collection of material occurred during a six-month period from June 1977 to January 1978. The major clinical signs were dyspnoea, failure to gain weight and sudden death in young animals. The cardiac defects included two patent ductus arteriosus, two anomalies of the coronary vessels, one persistent truncus arteriosus, one transposition of the aorta and pulmonary artery and one ventricular septal defect.

Published
1981

6. Measles Skin Test and Serologic Response to Intradermal Measles Antigen

Author

John D. Nelson, George Sandusky, and F. Bruce Peck

Subjects
business.industry, General Medicine, medicine.disease, Virology, Measles, Virus, Serology, Vaccination, Titer, Antigen, Immunity, Immunology, Medicine, Intradermal injection, business
Abstract

History of clinical measles is unreliable as an index of immunity because of subclinical infections, formes frustes, and other exanthems which may masquerade as measles. A skin test for reliably identifying individuals susceptible to measles could be useful for both selecting those requiring vaccination and for testing success of vaccination. This study was designed to relate reactivity to the intradermal injection of a measles antigen to history of clinical measles, to prior vaccination, and to the level of neutralizing and hemagglutination-inhibition antibodies. Another purpose was to determine whether a booster response in serum antibodies resulted from the skin test. Methods and Materials Skin Test Antigen.— The antigen was a tenfold concentration of formaldehyde-inactivated measles virus vaccine produced in chick-embryo tissue culture. The titer of virus before inactivation and concentration was 1 × 10 3.59 infectious doses per 0.5 ml. It did not contain adjuvant, but was preserved with 1:20,000 thimerosal

Published
1966

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