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Thomas J Fahey

Publications and source records attributed to Thomas J Fahey.

At least 19 recordsLinked to original sources
PubMed2026

Targeting ncRNA control networks with engineered exosomes to overcome therapy resistance in thyroid cancer.

Papillary thyroid cancer (PTC) is the most prevalent endocrine malignancy, accounting for over 90% of thyroid cancers. While differentiated thyroid cancers (DTCs) typically have favorable outcomes, a significant subset progresses to radioactive iodine-refractory (RAIR) disease, characterized by impaired iodine uptake and a 10-year survival rate below 10%. Genetic alterations and dysregulated signaling pathways underlie this transition. Non-coding RNAs (ncRNAs), including microRNAs (miRNAs), circular RNAs (circRNAs), and long non-coding RNAs (lncRNAs), play critical regulatory roles in tumor biology and may be transported via exosomes, facilitating intercellular communication and contributing to RAIR-PTC. This systematic review, conducted according to PRISMA 2020 guidelines, evaluated the role of exosomal ncRNAs in RAIR-PTC. A comprehensive search of PubMed, PubMed Central, and Google Scholar identified studies published within the past 15 years in English. Following stringent quality appraisal, studies with a non-bias score above 40% were included. Of 961 identified publications, 96 high-quality studies met inclusion criteria. Evidence indicates that therapy resistance in RAIR-PTC is driven by convergent ncRNA regulatory networks that suppress sodium-iodide symporter (NIS) expression and activate oncogenic pathways, most notably MAPK, PI3K/AKT/mTOR, and Wnt/β-catenin signaling. Multiple ncRNAs converge on key regulatory nodes, forming redundant circuits that sustain dedifferentiation, metabolic adaptation, and impaired iodide transport. Several consistently dysregulated ncRNAs directly or indirectly regulate NIS expression and trafficking, highlighting actionable targets. Exosomes emerge as biologically compatible, programmable delivery vehicles capable of transporting therapeutic ncRNA payloads independent of endogenous packaging mechanisms. These findings support a precision therapeutic paradigm in which engineered exosomes reprogram ncRNA networks to restore iodine-handling pathways and overcome therapy resistance in RAIR-PTC.

Humans↗
PubMed2006

Seminars: local and regional anesthesia for thyroid surgery.

BACKGROUND: Thyroid surgery is performed by a large number of surgeons with varying experience in thyroidectomy. The standard technique involves the use of general anesthesia, which provides patient comfort and virtually unlimited time to conduct the operation. Historically, thyroid surgery was conducted under local anesthesia by surgeons with significant expertise in the treatment of thyroid diseases. Over the past decade, there has been a renewed interest in the art of performing thyroidectomy under local/regional anesthesia in some specialized high volume endocrine surgery centers. METHODS: Here we review the indications and contraindications and technical considerations for performing thyroidectomy under local or regional anesthesia. RESULTS AND CONCLUSION: Local and regional anesthesia is safe and well tolerated for the majority of thyroid surgery.

Amides↗
PubMed2006

Splenic cord capillary hemangioma and anemia: resolution after splenectomy.

A 59-year-old female presented with isolated anemia and a splenic mass. Standard histology and immunohistochemical techniques categorized the splenic lesion as a cord capillary hemangioma. The patient's anemia resolved following splenectomy. Cord capillary hemangiomas are exceedingly rare with few reports in the literature. This is the first reported case of resolution of anemia after splenectomy for a vascular tumor of the spleen.

Anemia↗
PubMed2006

Microarray analysis of thyroid nodule fine-needle aspirates accurately classifies benign and malignant lesions.

Current preoperative diagnostic procedures for thyroid nodules rely mainly on the cytological interpretation of fine-needle aspirates (FNAs). DNA microarray analysis has been shown to reliably distinguish benign and malignant thyroid nodules in surgically resected specimens, but its diagnostic potential in thyroid FNA has not been examined. In the present study, the expression profiles of 50 benign thyroid lesions and papillary thyroid carcinoma tissue samples were compared, generating a list of 25 differentially expressed genes from this training set. A test set of 22 FNA specimens was evaluated by unsupervised hierarchical cluster analysis using this gene list, and the results were compared to FNA cytology. FNA specimens were found to fall into three clusters: malignant (n = 10), benign (n = 7), and indeterminate (n = 5). The benign and malignant groups showed complete concordance with the final histological diagnosis except for one histologically benign lesion, which was rediagnosed as follicular variant of papillary thyroid carcinoma on histological review. Paired analysis between FNA and matched tissues samples illustrated adequate sampling with FNA. These results illustrate that microarray analysis of FNA is feasible and has the potential to improve the accuracy of FNA in categorizing benign from malignant lesions beyond routine cytological evaluation.

Biopsy, Fine-Needle↗
PubMed2005

Molecular analysis of minimally invasive follicular carcinomas by gene profiling.

BACKGROUND: While the majority of minimally invasive follicular thyroid carcinoma (MIFTC) behave like follicular adenomas, some recur or metastasize. These studies were conducted to determine if molecular profiling can enhance our understanding of MIFTC and to perhaps offer a better classification schema. METHODS: Microarray analysis was performed on 27 follicular neoplasms. Thirteen follicular adenomas (FAs) were compared with 7 widely invasive follicular thyroid carcinomas (WIFTCs) to generate a list of differentially expressed genes. Next, 7 MIFTCs were analyzed along with the other samples in a cluster analysis. The MIFTCs were then compared directly against both the adenoma and WIFTC groups to investigate genetic relatedness. RESULTS: FAs and WIFTCs have distinct genetic profiles, with 401 differentially expressed genes. The 7 MIFTCs were added to the analysis. Six of 7 of the MIFTCs were grouped with the adenomas, 4 of which created their own subgroup. When analyzed directly, MIFTCs had 223 differently expressed genes, compared with FAs, and 365, compared with WIFTCs. CONCLUSIONS: Molecular profiling illustrates that the majority of MIFTCs comprise a subclass of follicular neoplasms, and, while most MIFTCs are genetically similar to adenomas, our patient data suggest that these tumors may deserve greater suspicion of malignant potential. Gene profiling can provide insight into the molecular pathogenesis of MIFTC.

Adenocarcinoma, Follicular↗
PubMed2005

Advancing the molecular diagnosis of thyroid nodules: defining benign lesions by molecular profiling.

BACKGROUND: Thyroid nodules are common and most are benign. Previous data from our laboratory and others has suggested that gene profiling can accurately distinguish between benign and malignant thyroid nodules and provide new leads in the study of thyroid tumorigenesis. Current preoperative techniques do not permit distinction between neoplastic and hyperplastic follicular neoplasms. These studies were undertaken to determine whether benign follicular tumors could be subcategorized by molecular profiling. METHODS: Molecular profiles of 8 follicular adenomas and 8 hyperplastic nodules were analyzed by oligonucleotide microarray analysis. A list of 402 differentially expressed genes was produced based on a comparison of these two groups. Seven additional benign follicular lesions were then added to the analysis. A hierarchical clustering analysis was performed on all 23 samples, utilizing the gene list generated from the test set, to examine the groups for potential differences and the ability of the gene list to distinguish tumor types. RESULTS: Cluster analysis of all 23 samples produced two distinct groups, one containing the adenomas and one containing the hyperplastic lesions. The analysis was able to identify follicular adenomas with a sensitivity of 84.6% and a specificity of 100%. CONCLUSIONS: These data indicate that benign thyroid lesions can be separated into distinct groups through molecular profiling. Analysis of the gene list may help further the understanding of thyroid tumorigenesis. Expression profiling may ultimately allow us to distinguish potentially malignant from benign follicular nodules.

Biomarkers↗
PubMed2004

Surgical site infection and the routine use of perioperative hyperoxia in a general surgical population: a randomized controlled trial.

CONTEXT: Surgical site infection (SSI) in the general surgical population is a significant public health issue. The use of a high fractional inspired concentration of oxygen (FIO2) during the perioperative period has been reported to be of benefit in selected patients, but its role as a routine intervention has not been investigated. OBJECTIVE: To determine whether the routine use of high FIO2 during the perioperative period alters the incidence of SSI in a general surgical population. DESIGN, SETTING, AND PATIENTS: Double-blind, randomized controlled trial conducted between September 2001 and May 2003 at a large university hospital in metropolitan New York City of 165 patients undergoing major intra-abdominal surgical procedures under general anesthesia. INTERVENTIONS: Patients were randomly assigned to receive either 80% oxygen (FIO2 of 0.80) or 35% oxygen (FIO2 of 0.35) during surgery and for the first 2 hours after surgery. MAIN OUTCOME MEASURES: Presence of clinically significant SSI in the first 14 days after surgery, as determined by clinical assessment, a management change, and at least 3 prospectively defined objective criteria. RESULTS: The study groups were closely matched in a large number of clinical variables. The overall incidence of SSI was 18.1%. In an intention-to-treat analysis, the incidence of infection was significantly higher in the group receiving FIO2 of 0.80 than in the group with FIO2 of 0.35 (25.0% vs 11.3%; P =.02). FIO2 remained a significant predictor of SSI (P =.03) in multivariate regression analysis. Patients who developed SSI had a significantly longer length of hospitalization after surgery (mean [SD], 13.3 [9.9] vs 6.0 [4.2] days; P<.001). CONCLUSIONS: The routine use of high perioperative FIO2 in a general surgical population does not reduce the overall incidence of SSI and may have predominantly deleterious effects. General surgical patients should continue to receive oxygen with cardiorespiratory physiology as the principal determinant.

Anesthesia, General↗
PubMed2004

Molecular analysis of Hurthle cell neoplasms by gene profiling.

BACKGROUND: Though Hurthle cell tumors are considered a variant of follicular lesions, recent data have suggested that Hurthle cell carcinomas may be more closely related to papillary thyroid carcinomas (PTCs). These studies were conducted to determine if molecular profiling can enhance our understanding of Hurthle cell neoplasms. METHODS: Thirteen Hurthle cell tumors (9 adenomas, 4 carcinomas) were analyzed with the Affymetrix HU-95 gene chips. Molecular profiles obtained were compared to 14 follicular adenomas (FAs), 7 follicular carcinomas (FCs), 10 PTCs, 11 follicular variant PTCs, and 9 hyperplastic nodules. Hierarchical cluster analysis defined potential groupings and differences among samples. RESULTS: Hurthle cell carcinomas grouped with FCs 100% of the time. Surprisingly, Hurthle cell adenomas clustered with FCs when compared to FAs and FCs in 8/9 (88%) cases. All 13 Hurthle cell lesions migrated as a distinct group separate from PTCs and FVPTCs. Finally, all Hurthle cell lesions clustered with FCs, rather than PTCs, when compared to both groups. CONCLUSIONS: Molecular profiles of Hurthle cell adenomas and carcinomas are more similar to FCs than benign lesions or PTCs. Although Hurthle cell adenomas generally behave in a benign fashion, the molecular signature of these lesions suggests a more malignant phenotype.

Adenocarcinoma, Follicular↗
PubMed2004

Discrimination of benign and malignant thyroid nodules by molecular profiling.

BACKGROUND: The evaluation of thyroid nodules by fine-needle aspiration has been the standard for almost 30 years, despite significant shortcomings in sensitivity and specificity. Recent data from our laboratory have suggested that molecular profiling permits the discrimination of specific types of thyroid nodules. These studies were undertaken to determine whether molecular profiling can discriminate between benign and malignant thyroid nodules with the necessary sensitivity and specificity required of a screening test. METHODS: Molecular profiles of 11 papillary thyroid carcinomas, 13 follicular variant of papillary thyroid carcinomas, 9 follicular thyroid carcinomas, and 26 benign tumors (follicular adenomas and hyperplastic nodules) were analyzed by oligonucleotide microarray analysis. A gene list was created based on 45 samples. Seventeen samples were then added to the analysis as unknowns. A hierarchical clustering analysis was performed on all 62 samples to examine the groups for potential differences and the ability of the gene list to distinguish tumor types. RESULTS: Cluster analysis of all 62 samples produced 2 distinct groups, 1 containing the carcinomas and 1 containing the benign lesions. The sensitivity for a diagnosis of cancer was 91.7% with a specificity of 96.2% (3 follicular variant of papillary thyroid carcinomas clustered with the benign lesions). The cancer gene profiles contained both known cancer-associated genes (MET, galectin-3) and previously unidentified genes. CONCLUSIONS: Molecular profiling readily distinguishes between benign and malignant thyroid tumors with excellent sensitivity and specificity. Elucidated genes may provide insight into the molecular pathogenesis of thyroid cancer. Gene profiling may significantly enhance the evaluation of thyroid nodules in the future.

Adult↗
PubMed2004

Molecular profiling distinguishes papillary carcinoma from benign thyroid nodules.

Recently we identified a molecular basis for differentiating benign and malignant follicular thyroid tumors. The purpose of these studies was to determine whether molecular analysis can be used to differentiate papillary thyroid carcinomas from benign thyroid nodules. Gene expression patterns of 14 papillary thyroid carcinomas and 21 benign tumors were analyzed by oligonucleotide array analysis. The carcinomas included seven classical papillary thyroid carcinomas (PTC) and seven follicular variant of PTC (FVPTC), and the benign tumors included 14 follicular adenomas and seven hyperplastic nodules. A hierarchical clustering analysis was performed to examine the groups for potential differences. The combined PTC and FVPTC groups had a distinct gene expression profile compared with the benign lesions. The sensitivity for a diagnosis of carcinoma was 93%, with a 100% specificity (one FVPTC clustered with the benign nodules). Cancer gene profiles contained both known (Met and galectin-3) and previously unidentified genes. Gene profiling is a reliable means of distinguishing PTC, FVPTC, and benign tumors of the thyroid. These gene profiles may provide insight into the pathogenesis of papillary thyroid carcinoma and may ultimately enhance the preoperative diagnosis of thyroid nodules on a molecular basis.

Carcinoma, Papillary↗
PubMed2003

Bile acids induce cyclooxygenase-2 expression in human pancreatic cancer cell lines.

To investigate a possible link between bile acids and the pathogenesis of pancreatic cancer, we determined whether conjugated or unconjugated bile acids induced cyclooxygenase-2 (COX-2) in two human pancreatic cancer cell lines, BxPC-3 and SU 86.86. Bile acids are known promoters of gastric and colon cancer. We demonstrated previously that COX-2, an enzyme that catalyzes the synthesis of prostaglandins, is over-expressed in human pancreatic adenocarcinoma. Both human pancreatic cell lines were treated with conjugated and unconjugated bile acids. COX-2 mRNA and protein were determined. In addition, prostaglandin E2 (PGE2) synthesis was measured. Treatment with conjugated or unconjugated bile acids for 3 h up-regulated COX-2 mRNA. Chenodeoxycholate (CD) or deoxycholate at concentrations ranging from 12.5 to 100 micro M caused a dose-dependent induction of COX-2 protein with a maximal effect at 100 micro M. Induction of COX-2 protein by CD and deoxycholate was detected after treatment for 6 h with maximal induction at 12 h. Taurochenodeoxycholate, a conjugated bile acid, also caused dose-dependent induction of COX-2 but higher concentrations of bile acid (200-1200 micro M) were required. Levels of cyclooxygenase-1 were unaffected by bile acid treatment. Unconjugated and conjugated bile acids caused 7- and 4-fold increases in PGE2 production, respectively. Taken together, these findings suggest a possible role for bile acids in the pathogenesis of pancreatic cancer.

Bile Acids and Salts↗
PubMed2003

Antisense hTERT inhibits thyroid cancer cell growth.

Activation of telomerase represents an early step in carcinogenesis. Increased telomerase expression in malignant thyroid tumors suggests that inactivation of telomerase may represent a potential chemotherapeutic target. The purpose of this study was to inhibit the protein component of telomerase, hTERT, in a human thyroid cancer cell line in vitro and in vivo using an antisense strategy. A 235-bp fragment of hTERT cDNA was subcloned, and sense and antisense hTERT expression vectors were constructed. These vectors were transfected into a human thyroid carcinoma cell line (FRO). Tumorigenic potential was determined by cellular growth assay, rate of apoptosis, anchorage-independent growth, and tumor growth in a nude mouse model. Significant down-regulation of hTERT expression was seen in the antisense transfected cells, compared with control and those transfected with the sense vector. A decrease in telomerase activity by TRAP assay was observed in the antisense hTERT cells but not in cells transfected with the sense hTERT construct. Inhibition of cell growth was observed after approximately 20 population doublings in the antisense-hTERT clones and was associated with an increase in the rate of apoptosis and a change in cellular morphology. Moreover, anchorage-independent growth was reduced in vitro, and tumor growth rate was diminished in vivo in the antisense hTERT clones. Inhibition of telomerase activity with antisense hTERT in human thyroid cancer cells is achievable and may represent a novel target to inhibit tumor growth.

Apoptosis↗
PubMed2003

Classification of follicular thyroid tumors by molecular signature: results of gene profiling.

PURPOSE: Thyroid nodules are common, with a lifetime risk of developing a clinically significant thyroid nodule of 10% or higher. Preoperative diagnosis was greatly enhanced by the introduction of fine needle aspiration in the 1970s, but there has been little advancement since that time. Discrimination between benign and malignant follicular neoplasms is currently not possible by fine needle aspiration and can even be difficult after full pathologic review. The purpose of these studies is to identify genes expressed in follicular adenomas and carcinomas of the thyroid that will permit molecular differentiation of these neoplasms. EXPERIMENTAL DESIGN: Gene expression patterns of 17 thyroid follicular tumors were analyzed by oligonucleotide array analysis. Gene profiles for follicular adenomas and carcinomas were identified, and the two groups were compared for differences in expression levels. The differentially expressed genes were used to perform a hierarchical clustering analysis training set. Five follicular tumors with diagnosis undisclosed to the investigators and 2 minimally invasive carcinomas were entered into the cluster analysis as a test set to determine whether diagnosis by gene profile correlated with that obtained by pathologic evaluation. RESULTS: Thyroid follicular adenomas and carcinomas showed strikingly distinct gene expression patterns. The expression patterns of 105 genes were found to be significantly different between follicular adenoma and carcinoma. Many uncharacterized genes contributed to the distinction between tumor types. For five follicular tumors for which the final diagnosis was undisclosed, the clustering algorithm gave the correct diagnosis in all 5 cases. CONCLUSIONS: Gene profiling is a useful tool to predict the molecular diagnosis of follicular thyroid tumors. Genes were identified that reliably differentiate follicular thyroid carcinoma from adenoma. This study provides insight into genes that may be important in the molecular pathogenesis of follicular thyroid tumors, as well candidates for preoperative diagnosis of follicular thyroid carcinoma.

Adenocarcinoma, Follicular↗