Expression of Thyroid Transcription Factor-1 and Ki-67 in the Thyroid Neoplasms

PURPOSE: Thyroid transcription factor-1 (TTF-1) has been known to regulate the transcriptional activity of thyroid-specific genes. Ki-67 has been known as a marker for indicating tumor growth. This study was designed to campare the expressions of TTF-1 and Ki-67 on non- neoplastic and neoplastic thyroid tissues. METHODS: The surgically resected specimens of various histological types of thyroid tumor, from the files of the Dept. of surgery, Chung-Ang University Pil-Dong Hospital, between January 1998 and June 2002 were reviewed, and 55 cases selected for immunohistochemical studies. The materials consisted of tissues from 10 nodular hyperplasias, 28 papillary carcinomas, 15 follicular adenomas and 12 follicular carcinomas. All specimens were routinely processed, and paraffin blocks were available in all cases. Immunohistochemical stains for TTF-1 and Ki-67 were also performed. RESULTS: In all the cases, including the nodular hyperplasias, papillary carcinomas, follicular adenomas and follicular carcinomas, expressions of the TTF-1 were observed. The properties of the TTF-1 expression, including staining intensity, extent and index were not related to the tumor type. The expression of TTF-1 was inversely correlated with the tumor proliferation fraction, as assessed by the Ki-67 staining index. CONCLUSION: TTF-1 was expressed in almost all the benign lesions and well differentiated carcinomas, and correlated with the tumor proliferation fraction.

Molecular characteristics of the inhibition of human neutrophil elastase by nonsteroidal antiinflammatory drugs

Nonsteroidal antiinflammatory drugs(NSAIDs) are known as clinically effective agents for treatment of inflammatory diseases. Inhibition of cyclooxygenase has been thought to be a major facet of the pharmacological mechanism of NSAIDs. However, it is difficult to ascribe the antiinflammatory effects of NSAIDs solely to the inhibition of prostaglandin synthesis. Human neutrophil elastase (HNElastase; HNE, EC 3.4.21.37) has been known as a causative factor in inflammatory diseases. To investigate the specific relationship between HNElastase inhibition and specificity of molecular structure of several NSAIDs, HNElastase was purified by Ultrogel AcA54 gel filtration, CM-Sephadex ion exchange, and HPLC (with TSK 250 column) chromatography. HNElastase was inhibited by aspirin and salicylate in a competitive manner and by naproxen, ketoprofen, phenylbutazone, and oxyphenbutazone in a partial competative manner, but not by ibuprofen and tolmetin. HNElastase-phenylbutazone-complex showed strong Raman shifts at 200, 440, 1124, 1194, 1384, 1506, and 1768 cm(-1). The Raman bands 1194, 1384, and 1768 cm(-1) may represent evidences of the conformational change at -N=N-phi radical, pyrazol ring, and -C=O radical of the elastase-drug complex, respectively. Phenylbutazone might be bound to HNElastase by ionic and hydrophobic interaction, and masked the active site. Inhibition of HNElastase could be another mechanism of action of NSAIDs besides cyclooxygenase inhibition in the treatment of inflammatory diseases. Different inhibition characteristics of HNE-lastase by NSAIDs such as aspirin, phenylbutazone-like drugs and ineffective drugs could be important points for drawing the criteria for appropriate drugs in clinical application.