ABSTRACT
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Subject(s)
Humans , Lung Neoplasms/pathology , Precancerous Conditions/pathology , Receptors, Vascular Endothelial Growth Factor , Neovascularization, Pathologic/pathology , Phenotype , Lymphangiogenesis , Biomarkers, Tumor/analysisABSTRACT
OBJECTIVE: To determine the telomerase activity in urine samples of patients with superficial bladder cancer, its sensitivity and specificity as a tumor marker, and possible implications for prognosis, diagnosis and therapeutic efficacy. METHODS: Urine samples of 50 patients with superficial bladder cancer were analyzed. Telomerase activity was determined by TRAP (telomeric repeat amplification protocol). Standard urinary cytology, urine culture and urinary sediment analysis were performed, as well as a pathological analysis of the surgical specimen. RESULTS: 84% of the patients were positive for telomerase activity and only 52% had a positive cytology. Telomerase activity showed a sensitivity and specificity of 73.6% and 92.7%, respectively, versus 53.2% and 81.8% for urinary cytology. The degree of cell differentiation and, to a lesser extent, bladder wall infiltration showed differences in comparison with conventional urinary cytology. CONCLUSIONS: Telomerase activity can be determined in voided urine samples of patients with superficial bladder cancer. It has a higher sensitivity and specificity than conventional urinary cytology and is a good marker for diagnosis and follow-up of these patients.
Subject(s)
Biomarkers, Tumor/metabolism , Telomerase/metabolism , Urinary Bladder Neoplasms/enzymology , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Sensitivity and Specificity , Urinary Bladder Neoplasms/pathologyABSTRACT
We have examined for the presence or absence of T cell receptor V-alpha (VA) and V-beta (VB) gene expression in infiltrating T lymphocytes (ITL) isolated from Graves' thyroid glands in comparison to paired peripheral blood lymphocyte (PBL) samples using a qualitative based polymerase chain reaction (PCR) assay. Sequence specific oligonucleotides for VA and VB T cell receptor gene (TCR) families that had previously been validated in other studies, were used for the PCR analysis, followed by Southern blot hybridization with a labelled, internal C-region primer. A total of seven Graves' disease patients who had been treated with carbimazole were studied. T cell receptor VA and VB gene usage was examined in freshly isolated, unstimulated ITLs from five patients. A widespread usage of VA and VB gene families with 12 to 18 families being used was apparent. Use of oligo-dT or C-region priming of the mRNA prior to reverse transcription of the mRNA did not have any significant affect on the results nor did the use of whole Graves' thyroid mRNA as the starting material (n = 2) or perfusion of one gland with saline to remove as much of the contaminating blood from the gland. Our results contrast with those of Davies and colleagues who have previously shown a restricted repertoire of VA gene families in ITLs in comparison to autologous PBLs, and are much more in line with other recent reports indicating a diverse VA repertoire of the infiltrating T cells in Graves' thyroid glands derived from patients treated with anti-thyroid drugs.
Subject(s)
Graves Disease/immunology , Receptors, Antigen, T-Cell, alpha-beta/genetics , Receptors, Antigen, T-Cell, alpha-beta/immunology , T-Lymphocytes/immunology , Thyroid Gland/immunology , Base Sequence , DNA Primers , Graves Disease/genetics , Humans , Molecular Sequence Data , Polymerase Chain Reaction , Thyroid Gland/cytologyABSTRACT
We have previously shown that ketoconazole may inhibit the androgen synthesis, but the risk to induce a blockade in the cortisol synthesis and/or hepatic abnormalities makes it mandatory to look for the least dose that is able to inhibit androgen production without inducing other abnormalities. To this end, we studied the levels of 17-alpha-hydroxyprogesterone (17, alpha-OH-P), dehydroepiandrosterone sulphate (DHEA-S), delta 4-androstenedione (delta 4-A), total (tT) and free (fT) testosterone, and the cortisol response to ACTH in 13 women with hyperandrogenism, before and after ketoconazole therapy at dosages of 400, 600, and 800 mg/day. Although with the 400 mg regimen a reduction in the levels of androstenedione and free and total testosterone was already observed, it was of small amount and it was not until the 600 mg regimen that androgen levels became normal. Thus, DHEAS-S was reduced from 3.672 +/- 1.013 to 2.216 +/- 756 ng/ml (p less than 0.05); delta 4-A was reduced from 392 +/- 80 to 283 +/- 79 ng/ml (p less than 0.01); tT was reduced from 1.5 +/- 0.78 to 0.7 +/- 0.1 ng/ml (p less than 0.05), and fT from 5.5 +/- 1.0 to 2.7 +/- 1.3 pg/ml (p less than 0.001). By contrast, 17 alpha-OH-P increased from 1.7 +/- 1.3 to 4.7 +/- 1.3 ng/ml (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
