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Adrenocortical tumors: Diagnosis, growth regulation and treatment
Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
1999 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Monoclonal antibodies generated by immunization with human adrenocortical cells reacted with the normal adrenal cortex, adrenocortical adenomas and carcinomas, but failed to stain a variety of normal tissues, renal cell carcinoma, and pheocromocytomas. The antibodies can be used to improve histological diagnosis and characterization of human adrenal lesions, and possibly for scintigraphic detection.

Insulin-like growth factor I (IGF-I) influences cellular growth, differentiation and secretion. IGF-I and its receptor were demonstrated in normal adrenal cortex, cortical adenomas and carcinomas, with intense and abundant expression in many carcinomas. Tumors causing aldosterone excess were IGF-I receptor negative. Recombinant IGF-I dose-dependently stimulated proliferation in human adrenocortical cancer cells, with reversal of the effect by IGF-I receptor antibodies. IGF-I may be an important stimulus for cell proliferation in adrenocortical tumors lacking discernible aldosterone excess.

Adrenal steroid converting enzymes were expressed in functioning and non-functioning adrenocortical adenomas. Cortical carcinomas had deficient enzyme expression, concurrent with abnormal urinary steroid profile and steroid hormone precursor excretion. Immunostaining for cortisol and sex steroids revealed variable expression, especially in the malignant lesions. Cortisol reactivity in aldosteronomas and non-functioning tumors indicates that the patients may be at risk to have suppressed adrenocortical function.

Adrenocortical carcinomas are associated with multidrug resistance related to a cell membrane expressed phosphoglycoprotein (Pgp) mediating extrusion of cytostatic drugs. Adrenocortical carcinomas displayed variable Pgp-immunoreactivity but universal cytostatic drug insensitivity in a fluorescent microculture cytotoxic assay (FMCA), substantiating that mechanisms other than Pgp may mediate resistance to cytostatic drugs in these tumors.

Fresh, non-cultured tumor-infiltrating lymphocytes (TIL cells) from two of three adrenocortical carcinomas showed significant lysis of autologous tumor cells. For one TIL cell preparation this activity was markedly enhanced by culture with interleukin-2. The TIL cells with cytolytic capacity mainly consisted of CD45RO+ T cells. Freshly isolated TIL cells strongly expressed TCR Vβ6 and Vβ8 genes, and in vitro cultured TIL lines demonstrated high percentage of CD8+ cells with these gene products. The results indicate possibilities to use transferred TIL cell lines in specific immunotherapy for adrenocortical carcinoma.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis , 1999. , 45 p.
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 0282-7476 ; 890
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URN: urn:nbn:se:uu:diva-1018ISBN: 91-554-4607-8OAI: oai:DiVA.org:uu-1018DiVA: diva2:160553
Public defence
1999-12-13, Gullstrandsalen, Uppsala University Hospital, Entrance 85, Uppsala, 09:15
Available from: 1999-11-22 Created: 1999-11-22Bibliographically approved

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