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- Aust, Gabriela, et al.
(författare)
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CD97: A dedifferentiation marker in human thyroid carcinomas
- 1997
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Ingår i: Cancer Research. - 0008-5472 .- 1538-7445. ; 57:9, s. 1798-1806
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Tidskriftsartikel (refereegranskat)abstract
- CD97 is a dimeric glycoprotein of Mr 75,000-85,000 and 28,000 belonging to a novel subfamily of seven-span transmembrane region leukocyte cell surface molecules. It is expressed abundantly in cells of hematopoietic origin. This is the first report demonstrating the expression of CD97 outside the hematopoetic system. CD97 was studied in normal human and neoplastic follicular epithelium of the thyroid and anaplastic (n = 3) and papillary (n = 1) thyroid carcinoma cell lines. In normal thyroid tissue (n = 11), no immunoreactivity of CD97 could be found, whereas in differentiated thyroid carcinomas (n = 10), CD97 expression was either lacking or low. Eleven of 12 undifferentiated anaplastic carcinomas revealed high CD97 presentation. CD97 was absent or only weakly present in patients with postoperative T1 tumors but increased greatly with the progression to postoperative T4 tumors. CD97 is clearly present in thyroid carcinoma cell lines but only at a very low level in normal human thyrocytes. Quantitation of CD97 cell surface expression levels revealed that C 643 and SW 1736 cells showed a two to four times higher specific antibody-binding capacity than did 8505 C and HTh 74 cells and a nearly 20 times higher specific antibody-binding capacity than normal thyrocytes. Phorbol 12-myristate 13-acetate treatment progressively caused a decrease of CD97 antigen expression in all cell lines to about 30% of their initial levels after 48 h. Immunohistochemical staining of SW 1736 cells revealed that CD97 is located in most of the cell compartments and suggested a CD97 internalization process after phorbol 12-myristate 13-acetate treatment. Semiquantitative reverse transcription-PCR showed a correlation of CD97 mRNA and cell surface CD97 expression level in the cell lines. SW 1736, HTh 74, and 8505 C cells apparently expressed CD97 with alternative glycosylation compared to peripheral lymphocytes, whereas most of the CD97 antigen presented on thyrocytes and C 643 cells had glycosylation sites resembling those of lymphocytes. The data suggest that CD97 expression may be a sensitive marker of dedifferentiation and of lymph node involvement in human thyroid tumors.
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| 2. |
- Mari, Andrea, et al.
(författare)
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Characterization of the Influence of Vildagliptin on Model-Assessed {beta}-Cell Function in Patients with Type 2 Diabetes and Mild Hyperglycemia.
- 2009
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 93:1, s. 103-109
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Tidskriftsartikel (refereegranskat)abstract
- Objective: This study was conducted to characterize the effects of vildagliptin on beta-cell function in patients with type 2 diabetes and mild hyperglycemia. Design: A 52-wk double-blind, randomized, parallel-group study comparing vildagliptin (50 mg qd) and placebo was conducted in 306 patients with mild hyperglycemia (A1C = 6.2-7.5%). Plasma glucose and C-peptide levels were measured during standard meal tests performed at baseline, wk 24 and 52, and after 4-wk washout. Insulin secretory rate (ISR) was calculated by C-peptide deconvolution and beta-cell function was quantified with a mathematical model that describes ISR as a function of absolute glucose levels (insulin secretory tone and glucose sensitivity), the glucose rate of change (rate sensitivity), and a potentiation factor. Results: Vildagliptin significantly increased fasting insulin secretory tone (between-group difference in adjusted mean change from baseline to wk 52 [Delta]= +34.1 +/- 9.5 pmol*min(-1) *m(-2), P<0.001) glucose sensitivity (Delta= +20.7 +/- 5.2 pmol*min(-1) *m(-2) *mM(-1), P < 0.001) and rate sensitivity (Delta= +163.6 +/- 67.0 pmol*m(-2) *mM(-1), P = 0.015) but total insulin secretion (ISR AUC0-2h) and the potentiation factor excursion during meals were unchanged. These improvements in beta-cell function were accompanied by a decrease in the glucose AUC0-2h (Delta = -1.7 +/- 0.5 mM*h, P = 0.002) and in A1C (Delta = -0.3 +/- 0.1%, P < 0.001). None of the effects of vildagliptin remained following 4-wk washout from study medication. Conclusions: Consistent with previous findings from shorter-term studies in patients with more severe hyperglycemia, in patients with mild hyperglycemia, improved beta-cell function is maintained throughout 52-wk treatment with vildagliptin and underlies a sustained improvement in glycemic control. However, no effects remain after washout.
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