RESUMO
BACKGROUND: Intraperitoneal (IP) perioperative chemotherapy with cisplatin is an interesting option in ovarian cancer treatment. A combination of cisplatin with IP epinephrine (already shown to improve IP and decrease systemic platinum (Pt) exposure) was evaluated using a population pharmacokinetic analysis. METHODS: Data from 55 patients treated with cisplatin-based IP perioperative chemotherapy with (n=26) or without (n=29) epinephrine were analysed using NONMEM. RESULTS: Epinephrine halves clearance between peritoneum and serum (IPCL) and increases the Pt central volume of distribution, IP exposure and penetration in tissue. IPCL has a better predictive value than any other parameter with respect to renal toxicity. CONCLUSION: This confirms that IPCL could be useful in assessing renal toxicity. As IPCL is also linked to tissue penetration and IP exposure, it may be proposed as biomarker. In addition to a Bayesian estimation, we propose a single-sample calculation-way to assess it. Prospective studies are needed to validate IPCL as a biomarker in this context.
Assuntos
Antineoplásicos/administração & dosagem , Cisplatino/administração & dosagem , Epinefrina/administração & dosagem , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/cirurgia , Peritônio/metabolismo , Adulto , Idoso , Antineoplásicos/sangue , Antineoplásicos/farmacocinética , Biomarcadores/sangue , Biomarcadores/metabolismo , Quimioterapia Adjuvante , Cisplatino/sangue , Cisplatino/farmacocinética , Esquema de Medicação , Epinefrina/sangue , Epinefrina/farmacocinética , Feminino , Humanos , Injeções Intraperitoneais , Período Intraoperatório , Taxa de Depuração Metabólica , Pessoa de Meia-Idade , Modelos Biológicos , Neoplasias Ovarianas/patologiaRESUMO
AIMS: To investigate the role of retinoic acid receptor beta (RAR beta) in thyroid carcinogenesis, we have investigated its expression in human thyroid samples by combined immunohistochemistry and Western blotting. METHODS AND RESULTS: Fifty-eight paraffin-embedded thyroid samples (40 normal or benign tissues, 16 papillary and two follicular carcinomas) were analysed by immunohistochemistry using a specific monoclonal antibody. Western blotting was also carried out on 11 selected samples (seven normal or benign tissues, three papillary carcinomas and one follicular carcinoma) and two human ovarian carcinomas as controls. RAR beta immunostaining was nuclear and limited to the normal epithelial thyroid tissue. A dramatic decrease in RAR beta immunostaining was observed in all the papillary carcinomas and in one follicular carcinoma. The other follicular carcinoma exhibited strong RAR beta immunostaining. By immunoblotting, a 51 kDa signal corresponding to the RAR beta was observed in nuclear extracts from normal thyroids and for one follicular carcinoma. However, this signal was lacking in the papillary carcinomas. These results were in complete agreement with the observations obtained by immunohistochemistry on the same samples. CONCLUSION: We present here the first demonstration of RAR beta protein in normal human thyroid follicular cells. In addition, we found that its expression is decreased in papillary thyroid carcinoma.