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1.
J Endocrinol Invest ; 46(7): 1449-1458, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-36646964

RESUMEN

PURPOSE: Adrenocortical carcinoma (ACC), a rare malignancy of the adrenocortex, is characterized by a crosstalk between the adipose microenvironment and tumor. Here, we assessed the involvement of carbonic anhydrase (CA) enzymes III and IX (CAIII and CAIX), in the metabolic alterations of the adipose tissue characterizing obesity and in the local crosstalk between the tumor adipose microenvironment and ACC. RESULTS/METHODS: CAIII and CAIX expression is altered in visceral adipose tissue (VAT) in obesity and in ACC. A significant CAIX upregulation was present in ACC at advanced stages (n = 14) (fold increase FI = 7.4 ± 0.1, P < 0.05) associated with lower CAIII levels (FI = 0.25 ± 0.06, P < 0.001), compared with lower stages (n = 9). In vitro coculture between visceral adipose stem cells (ASCs) and ACC cell lines, H295R and MUC-1, mimicking the interaction occurring between VAT and advanced ACC, showed a significant CAIX upregulation in H295R but not in MUC-1 cells, and a decreased expression of CAIII. The effect on adipose cells was different when cocultured with H295R or MUC-1 cells. Coculture did not modulate CAIII expression in ASCs, which, however, was significantly downregulated with H295R (FI = 0.34 ± 0.11, P < 0.05) and upregulated by MUC-1 when cocultured ASCs were induced to differentiate toward adipocytes, with an expression profile similar to what found in VAT of obese subjects. CAIX expression was markedly increased in ASCs cocultured with H295R and to a less extent following adipogenesis induction (FI = 150.9 ± 46.5 and FI = 4.6 ± 1.1, P < 0.01, respectively). CONCLUSION: Our findings highlight a modulation of CAIII and CAIX in the metabolic crosstalk between ACC and its local adipose microenvironment, suggesting that CAs might represent a potential target for novel anticancer therapies.


Asunto(s)
Neoplasias de la Corteza Suprarrenal , Carcinoma Corticosuprarrenal , Anhidrasa Carbónica III , Anhidrasas Carbónicas , Humanos , Anhidrasa Carbónica IX , Antígenos de Neoplasias/metabolismo , Anhidrasas Carbónicas/metabolismo , Obesidad , Microambiente Tumoral
2.
Org Biomol Chem ; 14(48): 11353-11356, 2016 Dec 28.
Artículo en Inglés | MEDLINE | ID: mdl-27892589

RESUMEN

A mild, efficient and one pot procedure to access benzoxazoles using easily accessible acylselenoureas as starting materials has been discovered. Mechanistic studies revealed a pH dependent intramolecular oxidative deselenization, with ring closure due to an intramolecular nucleophilic attack of a phenoxide ion. All the benzoxazoles herein reported possessed a primary sulfonamide zinc binding group and showed effective inhibitory action on the enzymes, carbonic anhydrases.


Asunto(s)
Amidas/farmacología , Benzoxazoles/farmacología , Inhibidores de Anhidrasa Carbónica/farmacología , Anhidrasas Carbónicas/metabolismo , Compuestos de Organoselenio/química , Urea/análogos & derivados , Amidas/síntesis química , Amidas/química , Benzoxazoles/síntesis química , Benzoxazoles/química , Inhibidores de Anhidrasa Carbónica/síntesis química , Inhibidores de Anhidrasa Carbónica/química , Relación Dosis-Respuesta a Droga , Humanos , Estructura Molecular , Oxidación-Reducción , Relación Estructura-Actividad , Urea/química
3.
Adv Exp Med Biol ; 457: 473-6, 1999.
Artículo en Inglés | MEDLINE | ID: mdl-10500824

RESUMEN

Vinorelbine (VNR) is a new semi-synthetic Vinca rosea alkaloid that has been employed both in combination and as a single agent, showing a significant antitumour activity. Since little is known about VNR in human leukemia, we studied the in vitro cytotoxic effect of VNR on peripheral blood lymphocytes from 18 patients affected by B-chronic lymphocytic leukemia (CLL), employing the INT assay. VNR inhibited fresh B-CLL cells from 15/18 patients in primary cultures, the ID50 doses ranging from 4 ng/ml to 83 micrograms/ml. These data strongly suggest that VNR could be effective in the treatment of B-CLL.


Asunto(s)
Antineoplásicos Fitogénicos/toxicidad , Linfocitos B/patología , Leucemia Linfocítica Crónica de Células B/patología , Vinblastina/análogos & derivados , Anciano , Linfocitos B/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Células Tumorales Cultivadas , Vinblastina/toxicidad , Vinorelbina
5.
C R Acad Hebd Seances Acad Sci D ; 282(22): 2015-20, 1976 Jun 14.
Artículo en Francés | MEDLINE | ID: mdl-821674

RESUMEN

Hamster embryo brain cells exposed in vitro for 24 hrs. to benzo (a) pyrene and then subcultivated. undergo a morphological transformation. After several passages, transformed cells are capable in most cases of inducing tumors of a special type through intraocular or intracerebral grafting. Histological characterisation of these tumors suggests that they are of glial type. Untreated control brain cells subcultivated for one year, keep their normal characteristics and do not induce tumors when grafted in Hamster.


Asunto(s)
Benzopirenos , Neoplasias Encefálicas/inducido químicamente , Transformación Celular Neoplásica , Animales , Encéfalo/embriología , Neoplasias Encefálicas/patología , Células Cultivadas , Cricetinae , Neoplasias del Ojo/patología , Técnicas In Vitro , Trasplante de Neoplasias
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