A5037724688- Cardiac tumors and thrombi
- Adrenal and Paraganglionic Tumors
- Sarcoma Diagnosis and Treatment
- Pituitary Gland Disorders and Treatments
- Cancer, Hypoxia, and Metabolism
- Peptidase Inhibition and Analysis
- Thyroid Cancer Diagnosis and Treatment
- Neuroblastoma Research and Treatments
- Glioma Diagnosis and Treatment
- Vascular Tumors and Angiosarcomas
- PI3K/AKT/mTOR signaling in cancer
- Hormonal Regulation and Hypertension
- Advanced Breast Cancer Therapies
- Neurofibromatosis and Schwannoma Cases
- Neuroendocrine Tumor Research Advances
- Growth Hormone and Insulin-like Growth Factors
- Protein Kinase Regulation and GTPase Signaling
- Cancer-related Molecular Pathways
- Cell Adhesion Molecules Research
- Cancer-related gene regulation
- Drug Transport and Resistance Mechanisms
- Bone Tumor Diagnosis and Treatments
- Adrenal Hormones and Disorders
- Melanoma and MAPK Pathways
- Metabolism, Diabetes, and Cancer
The Ohio State University
2015-2025
Twitter (United States)
2024
The Ohio State University Wexner Medical Center
2007-2022
Clinical Research Management
2022
The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute
2016-2021
Cancer Genetics (United States)
2005-2017
Bristol-Myers Squibb (Germany)
2017
Eisai (United Kingdom)
2017
GTx (United States)
2016
Diabetes Australia
2012
Cushing's syndrome (CS) is a disorder associated with significant morbidity and mortality due to prolonged exposure high cortisol concentrations. Our objective was evaluate the safety efficacy of mifepristone, glucocorticoid receptor antagonist, in endogenous CS. We conducted 24-wk multicenter, open-label trial after failed multimodality therapy at 14 U.S. academic medical centers three private research centers. Participants included 50 adults CS type 2 diabetes mellitus/impaired glucose...
The "complex of myxomas, spotty skin pigmentation, and endocrine overactivity," or "Carney complex" (CNC), is caused by inactivating mutations the regulatory subunit type 1A cAMP-dependent protein kinase (PRKAR1A) gene as yet unknown defect(s) in other gene(s). Delineation a genotype-phenotype correlation for CNC patients essential understanding PRKAR1A function providing counseling preventive care.A transatlantic consortium studied molecular genotype clinical phenotype 353 (221 females 132...
Carney complex (CNC) is an autosomal dominant multiple neoplasia syndrome, which has been linked to loci on 2p16 and 17q22-24. We recently reported that PRKAR1A, codes for the type 1A regulatory subunit of protein kinase A (PKA), a tumor suppressor gene chromosome 17 mutated in some CNC families. To evaluate spectrum PRKAR1A mutations, we identified its genomic structure screened mutations 54 kindreds (34 families 20 patients with sporadic disease). Fourteen were informative linkage...
Background: Primary pigmented nodular adrenocortical disease causes the Cushing syndrome in children and young adults is most frequently associated with Carney complex. Objective: To evaluate diagnostic tests for primary disease. Design: Retrospective cohort study. Setting: Tertiary care center. Patients: 21 patients The control groups consisted of 9 macronodular 15 unilateral (single adenomas). Measurements: Clinical characteristics, radiologic imaging, a 6-day Liddle test determination...
Background —Intracardiac myxomas are significant causes of cardiovascular morbidity and mortality through embolic stroke heart failure. In the autosomal dominant syndrome Carney complex, intracardiac arise in setting lentiginosis other lesions associated with cutaneous hyperpigmentation, extracardiac myxomas, nonmyxomatous tumors. Genetic factors that regulate cardiac tumor growth remain unknown. Methods Results —We used molecular genetic techniques linkage analysis to study 4 kindreds...
Abstract Carney complex is an autosomal dominant neoplasia syndrome characterized by spotty skin pigmentation, myxomatosis, endocrine tumors, and schwannomas. This condition may be caused inactivating mutations in PRKAR1A, the gene encoding type 1A regulatory subunit of protein kinase A. To better understand mechanism which PRKAR1A cause disease, we have developed conventional conditional null alleles for Prkar1a mouse. Prkar1a+/− mice nonpigmented schwannomas fibro-osseous bone lesions...
ACTH-independent macronodular adrenal hyperplasia (AIMAH) is often associated with subclinical cortisol secretion or atypical Cushing's syndrome (CS). We characterized a large series of patients AIMAH and compared them other adrenocortical tumors.We recruited 82 subjects with: 1) (n = 16); 2) cortisol-producing adenoma CS 15); 3) aldosterone-producing 19); 4) single adenomas clinically nonsignificant 32).Urinary free (UFC) 17-hydroxycorticosteroid (17OHS) were collected at baseline during...
Abstract Context Systemic treatment of metastatic adrenocortical carcinoma (ACC) remains limited to chemotherapy and mitotane. Preliminary evidence suggesting that antitumor immune responses can be elicited in ACC has fostered interest checkpoint inhibitors such as anti–PD-1 nivolumab. Objective The primary endpoint was objective response rate according the evaluation criteria solid tumors. Secondary endpoints were progression-free survival (PFS), overall survival, safety. Design Single-arm,...
Carney complex (CNC) is a familial multiple neoplasia and lentiginosis syndrome with features overlapping those of McCune-Albright (MAS) other endocrine (MEN) syndromes, MEN type 1 (MEN 1), in particular. GH-producing pituitary tumors have been described individual reports at least two large CNC patient series. It has suggested that the evolution acromegaly resembles manifestations its chronic, often indolent, progressive nature. However, histologic molecular evidence not presented support...
Increased extraglandular aromatization has been reported as the cause of familial gynecomastia. We studied a kindred with aromatase excess inherited in an autosomal dominant manner, which affected males had heterosexual precocity and/or gynecomastia, and females isosexual macromastia. The propositus was 9-yr-old boy His 7.5-yr-old sister precocious puberty, their father paternal grandmother peripubertal gynecomastia macromastia, respectively. Serum concentrations gonadal adrenal steroid...
In multidrug-resistant mouse J774.2 cells, the differential overproduction of functionally distinct phosphoglycoprotein isoforms reflects amplification or transcriptional activation both two mdr gene family members, mdr1a and mdr1b. The is a complex unit whose expression associated with multiple transcript sizes. Independently selected cell lines differentially overexpress either 4.6- 5.0-kilobase (kb) 4.7- 5.1-kb transcripts. However, abundant product was observed only in which...
Carney complex (CNC) is an inherited neoplasia syndrome with endocrine overactivity. Its most frequent manifestation primary pigmented nodular adrenocortical disease (PPNAD), a bilateral hyperplasia causing pituitary-independent Cushing's syndrome. Inactivating mutations in PRKAR1A, gene encoding the type 1 alpha-regulatory subunit (R1alpha) of cAMP-dependent protein kinase (PKA) have been found 80% CNC patients To demonstrate implication R1alpha loss initiation and development PPNAD, we...
Some cancers have been stratified into subclasses based on their unique involvement of specific signaling pathways. The mapping human cancer genomes is revealing a vast number somatic alterations; however, the identification clinically relevant molecular tumor and respective driver genes presents challenges. This information key to developing more targeted personalized therapies. Here, we generate new mouse model genomically unstable osteosarcoma (OSA) that phenocopies disease. Integrative...
The development of diabetes insipidus (DI) following transsphenoidal resection pituitary adenomas has been associated with higher postsurgical morbidity and longer hospitalizations. Identifying these patients promptly efficiently can lead to improved health care outcomes.We evaluated our institution's incidence DI adenoma assessed for preoperative risk factors that were postoperative DI.A retrospective review 271 who underwent endoscopic endonasal a between July 2010 December 2016 by single...
Mutations of the human type Ialpha regulatory subunit (RIalpha) cyclic AMP-dependent protein kinase (PKA; PRKAR1A) lead to altered activity, primary pigmented nodular adrenocortical disease, and tumors thyroid other tissues. To bypass early embryonic lethality Prkar1a(-/-) mice, we established transgenic mice carrying an antisense transgene for Prkar1a exon 2 (X2AS) under control a tetracycline-responsive promoter. Down-regulation by up 70% was achieved in mouse tissues fibroblasts, with...