Gene expression profiling associated with the progression to poorly differentiated thyroid carcinomas

Poorly differentiated thyroid carcinomas (PDTC) represent a heterogeneous, aggressive entity, presenting features that suggest a progression from well-differentiated carcinomas. To elucidate the mechanisms underlying such progression and identify novel therapeutic targets, we assessed the genome-wide expression in normal and tumour thyroid tissues.info:eu-repo/semantics/publishe

Poorly differentiated and anaplastic thyroid carcinomas: chromosomal and oligo-array profile of five new cell lines

Information on gene alterations associated to poorly differentiated (PDTC) and anaplastic thyroid carcinomas (ATC) is scarce. Using human cancer cell lines as a tool for gene discovery, we performed a cytogenetic and oligo-array analysis in five new cell lines derived from two PDTC and three ATC. In PDTC we evidenced, as important, the involvement of the MAPK/ERK kinase pathway, and downregulation of a group of suppressor genes that include E-cadherin. In ATC, downregulation of a specific group of oncosuppressor genes was also observed. Our ATC cell lines presented chromosomal markers of gene amplification, and we were able to identify for the first time the nature of the involved amplicon target genes. We found that the main molecular differences between the two cell line types were related to signal transduction pathways, cell adhesion and motility process. TaqMan experiments performed for five amplicon target genes and for two genes, which allowed a clear distinction between ATC and PDTC: CDH13 and PLAU corroborated array results, not only in the cell lines, but also in an additional set of primary 14 PDTC and three ATC. We suggest that our findings may represent new tools for the development of more effective therapies to the hitherto untreatable ATC

Refractory chronic sinusitis: evaluation of symptom improvement after Denker's procedure

OBJECTIVES: Although there is ample literature describing various aspects of functional endoscopic sinus surgery (FESS) in relationship to its success rates, very little has been reported regarding possibilities in case of recurrent failure. We investigated subjective results of Denker's procedure used as a last resort for refractory chronic rhinosinusitis/polyposis. STUDY DESIGN AND SETTING: A retrospective questionnaire-based study of 82 patients who underwent Denker's procedure between 1986 and 1997 at the Erasmus University Medical Center, The Netherlands, was conducted. RESULTS: Eighty-four percent of patients reported reduction of overall symptomatology. A significant reduction of nasal obstruction, headache, feeling of fullness, post-nasal drip, rhinorrhoea, facial pain, dental pain, and coughing was reported. In addition, symptoms of lower airway inflammation did improve significantly in asthmatic patients. CONCLUSIONS: These data suggest that radical surgery using Denker's approach should be considered in selected cases after recurrent failure of functional sinus surgery. SIGNIFICANCE: A prospective study is warranted to validate this approach for refractory chronic rhinosinusiti

Patterns of expression of cell cycle/apoptosis genes along the spectrum of thyroid carcinoma progression

Genetic screening studies suggest that genetic changes underlie progression from well differentiated to anaplastic thyroid cancers. The aim of this study is to determine to what extent cell cycle/apoptosis regulators contribute to cancer progression. Tissue microarrarys (TMAs) were constructed from well-differentiated papillary thyroid carcinoma (WDPTC; n = 41), poorly differentiated thyroid carcinoma (PDTC; n = 43), and anaplastic thyroid carcinoma (ATC; n = 22). TMAs were immunostained for 7 different cell cycle/apoptosis-related genes (p53, Ki-67, bcl-2, mdm-2, cyclin D1, p21, and p27). p53 (0%, 12%, 32%) and Ki-67 (5%, 49%, 82%) were expressed with increasing frequency, and bcl-2 (68%, 42%, 0%) and p21 (40%, 7%, 0%) with decreasing frequency in WDPTC to PDTC and ATC, respectively (P < .001). Interestingly, mdm-2 (54%, 5%, 0%) showed decreased expression along the progression axis (P < .001). p27 and cyclin D1 were expressed in <15% of cases, with a trend toward decreasing expression from WDPTC to PDTC to ATC. These data confirm the presence of increasing genetic complexity with progressive dedifferentiation in thyroid cancer, with aberrant tumor suppressor activity and increased proliferative activity being most prevalent in ATC. The data also confirm the intermediate position of PDTC in the classification scheme of thyroid carcinoma

Het syndroom van Lemierre en de neurologische complicaties

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