Domizia Debernardis

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The quinazoline folate analogue raltitrexed (ZD1694; Tomudex) and the camptothecin derivative irinotecan are two new agents showing clinical activity against colorectal cancer. To identify the optimal conditions to achieve synergistic cytotoxicity before the clinical development of their combination, we explored the interactions between ZD1694 and the(More)
PURPOSE To determine whether immunohistochemical thymidylate synthase (TS) quantitation predicts for clinical outcome in patients with advanced colorectal cancer treated by fluorouracil (FUra)-based chemotherapy. PATIENTS AND METHODS TS levels were measured immunohistochemically on archival specimens of colorectal cancer metastases from 48 patients(More)
Nine human ovarian cancer cell lines that express wild-type (wt) or mutated p53 were used to evaluate the cytotoxicity induced by paclitaxel. The IC50 calculated in the five mutated p53-expressing cell lines was not different from the four wt p53-expressing cell lines. The introduction of wt p53, by using a temperature-sensitive mutant murine p53 or the(More)
The ’nicotinamide adenine dinucleotide phosphate diaphorase’ histochemical technique was used as a marker of neuronal nitric oxide synthase to assess the presence of the enzyme in the anterior hypothalamus of the rat. Particular attention was focused on the subparaventricular zone, periventricular area and suprachiasmatic nucleus. The results show that(More)
Recently, we have demonstrated that thymidylate synthase (TS) protein expression predicts for the clinical response to a regimen of infusional 5-fluorouracil (5FU) in advanced colorectal cancer patients. Previous studies by other groups that showed a correlation between TS gene expression and response to the fluoropyrimidine also involved infusional(More)
BACKGROUND Different 5-fluorouracil (5-FU) schedules and/or biochemical modulators may result in different mechanisms of cytotoxicity, potentially affecting the correlation between thymidylate synthase (TS) expression and the clinical response to the fluoropyrimidine. PATIENTS AND METHODS TS levels were measured immunohistochemically on archival specimens(More)
BACKGROUND We assessed the hypothesis that a compromised p53 function could account for the non response of colon cancer patients with low thymidylate synthase (TS) expression receiving a bolus 5-fluorouracil (5-FU) leucovorin (LV) combination. PATIENTS AND METHODS The study population consisted of 41 patients with unresectable metastatic colon cancer,(More)
Taxol is an antitumor drug which, as its mechanism of action, promotes microtubule assembly in vitro. Camptothecin (CPT) is an anticancer agent with the peculiar mechanism of poisoning eukaryotic DNA topoisomerase I. Both drugs are in clinical trials and their chemotherapeutic efficacy seems promising in refractory human ovarian cancer. We studied the(More)
Seven ovarian and one cervical human cancer cell lines were examined far their sensitivity or resistance to tumor necrosis factor, to three topoisomerase II inhibitors and to cisplatin. Only one line exhibited the multidrug-resistance phenotype and another one an 'atypical'-MDR phenotype. The combination of TNF and topoisomerase-II inhibitors produced(More)
Thymidylate synthase (TS) expression in colorectal cancer metastases has been shown to predict for the clinical response to 5-fluorouracil. Because primary tumors may easily provide accessible sources of tissue for marker analysis, we have investigated the stability of TS expression between primary colorectal cancer and the corresponding distant metastases(More)