title: Monitoring response to cytostatic cisplatin in a HER2(+) ovary cancer model by MRI and in vitro and in vivo MR spectroscopy.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors: Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Roma, Italy.
authors: M E
authors: ME
authors: Pisanu
authors: Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Roma, Italy.
authors: A
authors: A
authors: Ricci
authors: Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Roma, Italy.
authors: L
authors: L
authors: Paris
authors: Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Roma, Italy.
authors: E
authors: E
authors: Surrentino
authors: 1] Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Amadeo 42, 20133 Milano, Italy [2] Department of Histology, University of Medicine and Pharmacy 'Grigore T. Popa', Iasi, Romania.
authors: L
authors: L
authors: Liliac
authors: Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Amadeo 42, 20133 Milano, Italy.
authors: M
authors: M
authors: Bagnoli
authors: Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Amadeo 42, 20133 Milano, Italy.
authors: S
authors: S
authors: Canevari
authors: Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Amadeo 42, 20133 Milano, Italy.
authors: D
authors: D
authors: Mezzanzanica
authors: Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Roma, Italy.
authors: F
authors: F
authors: Podo
authors: Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Roma, Italy.
authors: E
authors: E
authors: Iorio
authors: Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Roma, Italy.
authors: R
authors: R
authors: Canese
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000008:administration & dosage; D054697:Cytostatic Agents / Q000008:administration & dosage; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D051379:Mice; D010051:Ovarian Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D011859:Radiography; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis / Q000235:genetics*; D023041:Xenograft Model Antitumor Assays
chemical_list: D002945:Cisplatin; D054697:Cytostatic Agents; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human