A5074454934- Thyroid Cancer Diagnosis and Treatment
- Thyroid Disorders and Treatments
- Cancer-related Molecular Pathways
- PI3K/AKT/mTOR signaling in cancer
- Growth Hormone and Insulin-like Growth Factors
- Genetic factors in colorectal cancer
- Protein Kinase Regulation and GTPase Signaling
- Immune Response and Inflammation
- Estrogen and related hormone effects
- Telomeres, Telomerase, and Senescence
- Extracellular vesicles in disease
- Hypothalamic control of reproductive hormones
- Cytokine Signaling Pathways and Interactions
- Cancer-related molecular mechanisms research
- Cancer, Hypoxia, and Metabolism
- Neuropeptides and Animal Physiology
- Cancer Mechanisms and Therapy
- NF-κB Signaling Pathways
- Cancer-related gene regulation
- T-cell and B-cell Immunology
- Wnt/β-catenin signaling in development and cancer
- interferon and immune responses
- S100 Proteins and Annexins
- BRCA gene mutations in cancer
- Cell Adhesion Molecules Research
The Ohio State University
2010-2020
The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute
2005-2020
The Ohio State University Wexner Medical Center
2008-2019
Cancer Genetics (United States)
2004-2017
Diabetes Australia
2011-2017
Uniformed Services University of the Health Sciences
2008-2011
National Cancer Institute
1991-2011
North Carolina State University
2011
AstraZeneca (United Kingdom)
2011
Emory University
2011
Purpose Based on the pivotal role of Ras-Raf-MAP-ERK signaling and vascular endothelial growth factor (VEGF) in papillary thyroid cancer (PTC), we conducted a phase II clinical trial sorafenib targeting RAF VEGF receptor kinases PTC. Patients Methods The primary end point was objective response rate. Secondary points included correlation with serum thyroglobulin (Tg); functional imaging; tumor genotype; inhibition biopsies. Using Simon minimax two-stage design, 16 or 25 chemotherapy-naïve...
Purpose Mutations in the RET proto-oncogene and vascular endothelial growth factor receptor (VEGFR) activity are critical pathogenesis of medullary thyroid cancer (MTC). Sorafenib, a multikinase inhibitor targeting Ret VEGFR, showed antitumor preclinical studies MTC. Patients Methods In this phase II trial sorafenib patients with advanced MTC, primary end point was objective response. Secondary points included toxicity assessment response correlation tumor markers, functional imaging,...
Papillary thyroid carcinomas (PTCs) that invade into local structures are associated with a poor prognosis, but the mechanisms for PTC invasion incompletely defined, limiting development of new therapies. To characterize biological processes involved in invasion, we analyzed gene expression profiles microscopically dissected intratumoral samples from central and invasive regions seven widely PTCs normal tissue by oligonucleotide microarray performed confirmatory functional studies. In...
Biliary cancers (BCs) carry a poor prognosis, but targeting the RAS/RAF/mitogen-activated protein kinase (MEK)/extracellular signal-related (ERK) pathway is of significance. Selumetinib an inhibitor MEK1/2, so this trial was designed to determine safety and efficacy selumetinib in BC.
A rat thyrotropin (thyroid-stimulating hormone, TSH) receptor cDNA was isolated that encoded a protein of 764 amino acids, Mr 86,528. Transfection the caused COS-7 cells to develop TSH-sensitive adenylate cyclase response and ability bind 125I-labeled TSH; both activities were similar those FRTL-5 thyroid not duplicated by lutropin. The gene represented assigned mouse chromosome 12 human 14. Northern analyses identified two species mRNA, 5.6 3.3 kilobases, in cells; transcripts appeared...
Extracellular vesicles (EV), including exosomes and shed vesicles, have been implicated in intercellular communication; however, their biomarker potential is less clear. Therefore, EVs derived from MCF7 MCF10A cells were analyzed to identify unique miRNA (miR) profiles that distinguish origin. One characteristic common the miR of parent high abundance miR-21, let-7a, miR-100, miR-125b, low levels miR-205. A second "miRNA-like" tRNA fragments, which EVs, not found comparing cellular profiles....
Thyroid carcinoma is a common endocrine cancer with favorable prognosis if subjected to timely treatment. However, the clinical identification of follicular thyroid (FTC) among patients benign nodules still challenge. Preoperative fine needle aspiration-based cytology cannot always differentiate carcinomas from neoplasias. Because current methods fail improve preoperative diagnosis nodules, new molecular-based diagnoses should be explored. We conducted microarray-based study reveal genetic...
Albright hereditary osteodystrophy is caused by heterozygous inactivating mutations in GNAS, a gene that encodes not only the α-chain of Gs (Gαs), but also NESP55 and XLαs through use alternative first exons. Patients with GNAS on maternally inherited alleles are resistant to multiple hormones such as PTH, TSH, LH/FSH, GHRH, glucagon, whose receptors coupled Gs. This variant termed pseudohypoparathyroidism type 1a due presumed tissue-specific paternal imprinting Gαs. Previous studies have...
MicroRNA (miR) expression signatures are proposed to be able differentiate thyroid cancer from benign lesions. We selected eight miRs (miR-146b, -221, -187, -197, -346, -30d, -138, and -302c) examine the potential use of supplement diagnostic cytology in cases designated as "atypia undetermined significance."miR was measured fine needle aspiration (FNA) specimens by quantitative polymerase chain reaction. Gene analyses linear discriminant analysis (LDA) were performed a training sample set...
Background:Papillary thyroid carcinoma (PTC) shows high heritability, yet efforts to find predisposing genes have been largely negative.
Exosome size distributions and numbers of exosomes released per cell are measured by asymmetric flow-field flow fractionation/multi-angle light scattering (A4F/MALS) for three thyroid cancer lines as a function treatment that inhibits MAPK signaling pathways in the cells. We show these release with well-defined morphological features reflect common biological process their formation into extracellular environment. find those constitutive activation pathway display MEK-dependent exosome...
The PTEN (MMAC1/TEP1) tumor suppressor gene was recently isolated and mapped to human chromosome band 10q23. Homozygous deletions mutations of were observed in cell lines sporadic cancers the breast, kidney, central nervous system. Germline found Cowden disease, an autosomal dominant inherited syndrome, previously bands 10q22–23. This disease is associated with a wide variety malignancies hamartomas ectodermal, mesodermal, endodermal origin. most common neoplasms patients arise skin, thyroid...
The development of distant metastasis is the most important predictor death from thyroid cancer. KiSS-1 a recently cloned human suppressor gene whose product, metastin, was identified as endogenous agonist for novel Gq/11 coupled receptor (metastin receptor). expression and functional consequences metastin have not been evaluated in We measured mRNA levels 10 FCs 13 papillary carcinomas (PCs), 2 benign non-functioning follicular adenomas (FAs), 11 normal samples, signaling pathways activated...
The chimeric chloramphenicol acetyltransferase (CAT) construct, pTRCAT5'-199, containing the TSH receptor (TSHR) minimal promoter, -199 to -39 base pairs (bp), exhibits thyroid specificity and TSH/cAMP autoregulation evident in TSHR gene expression. present report shows that a cis-acting element between -189 -175 bp, which binds transcription factor-1 (TTF-1), is involved both activities. 22 bp -178 contains positive important for expression of promoter rat FRTL-5 cells. DNAase I...
The phosphatidylinositol 3-kinase/AKT pathway is crucial to many cell functions, and its dysregulation in tumors a common finding. molecular basis of follicular thyroid cancer metastasis not well understood but may also be influenced by AKT activation. We previously created knockin mutant mouse that expresses hormone receptor-beta gene (TRbetaPV mouse) spontaneously develops distant similar human cancer. In this study, we investigated whether our model exhibits activation as Western blot...
Constitutive activation of serine/threonine kinase Akt causes uncontrolled cell-cycle progression in different cell types and malignancy. To investigate how modulates vascular smooth muscle cells (SMCs) vitro the intact animal, we inhibited Akt-dependent signaling by adenovirus-mediated transfection a dominant-negative mutant (AA-Akt). We observed reduced proliferation rate ( P <0.01), DNA synthesis significant arrest G1/S exit <0.01) both response to serum stimulation vivo after...
Toll-like receptors (TLRs) initiate an innate immune response. TLR3 on dendritic cells recognize double-stranded (ds) RNA and then signal increases in cytokines recognition molecules important for cell interactions. In this report, we demonstrate mRNA protein are expressed Fisher rat thyroid line-5 (FRTL-5) functional because incubating with polyinosine-polycytidylic acid causes 1) transcriptional activation of both the nuclear factor kappaB (NF-kappaB)/Elk1 interferon (IFN) regulatory...