RESUMEN
BACKGROUND: Limited knowledge is available on alterations induced by cytostatic drugs on magnetic resonance spectroscopy (MRS) and imaging (MRI) parameters of human cancers, in absence of apoptosis or cytotoxicity. We here investigated the effects of a cytostatic cisplatin (CDDP) treatment on (1)H MRS and MRI of HER2-overexpressing epithelial ovarian cancer (EOC) cells and in vivo xenografts. METHODS: High-resolution MRS analyses were performed on in vivo passaged SKOV3.ip cells and cell/tissue extracts (16.4 or 9.4 T). In vivo MRI/MRS quantitative analyses (4.7 T) were conducted on xenografts obtained by subcutaneous implantation of SKOV3.ip cells in SCID mice. The apparent diffusion coefficient (ADC) and metabolite levels were measured. RESULTS: CDDP-induced cytostatic effects were associated with a metabolic shift of cancer cells towards accumulation of MRS-detected neutral lipids, whereas the total choline profile failed to be perturbed in both cultured cells and xenografts. In vivo MRI examinations showed delayed tumour growth in the CDDP-treated group, associated with early reduction of the ADC mean value. CONCLUSION: This study provides an integrated set of information on cancer metabolism and physiology for monitoring the response of an EOC model to a cytostatic chemotherapy, as a basis for improving the interpretation of non-invasive MR examinations of EOC patients.
Asunto(s)
Imagen por Resonancia Magnética/métodos , Espectroscopía de Resonancia Magnética/métodos , Neoplasias Ováricas/tratamiento farmacológico , Receptor ErbB-2/genética , Animales , Línea Celular Tumoral , Cisplatino/administración & dosificación , Citostáticos/administración & dosificación , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Ratones , Neoplasias Ováricas/diagnóstico por imagen , Neoplasias Ováricas/genética , Neoplasias Ováricas/patología , Radiografía , Receptor ErbB-2/biosíntesis , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Starting from the information on ovarian cancer provided by the mainstream publications, we construct a review focusing on the following issues: (i) the genetic profile, (ii) the role of the epithelial-mesenchymal transition in the acquirement of malignant features, (iii) the controversial hypothesis regarding the origin, and (iv) the involvement of the immune system in the tumoral microenvironment. Advances in the decipherment at the genetic level in the pathogenic mechanisms progressively lead to the idea of a genetic signature for the ovarian cancer. Moreover, the complementary approaches oriented towards the decryption of the intrinsic structure of the expressed molecules and, implicitly, the development of proteomics open new perspectives for an early diagnosis and an appropriate treatment. The research on the epithelial-mesenchymal transition (mainly those exploring the signaling pathways responsible for the switch between the loss of the epithelial characteristics and the gain of a mesenchymal cell phenotype, with results in the amplification of differentiation, motility and tumoral invasion) allow a deeper understanding of the complex pathogenic mechanism which governs ovarian carcinogenesis. The classic conception of ovarian cancer pathogeny, based on the role of the ovarian surface epithelium, is currently reconsidered, and a novel hypothesis is formulated, which supports direct involvement of the Fallopian tubes for the serous type. Although recent research suggests the implication of immune/inflammatory cells by specific mechanisms in ovarian cancer pathogenesis, there is yet reliable evidence concerning their modality of direct action and/or modulation of tumoral growth. Thus, ovarian carcinogenesis remains a research challenge, due to still numerous unknown factors involved in the malignant transformation sequences, originating from the genetic-molecular alterations and reflected by cellular and tissue expression patterns.