1; 1respectively. We then compared both the molecular profiles of chemosensitivityto the clinical response to the intravesical regimen adopted inthe first 6 months of follow up.RESULTS: This chemosensitivity test was able to predict responseto treatment in 93% of patients. The assay is easy to performwith low costs and rapid time of execution.CONCLUSIONS: Our results are encouraging in the view of anindividualised therapeutic approach, to provide a higher treatmentsuccess rate while sparing patients unnecessary toxicity from drugsthat are not suited for their tumors.; INTRODUCTION AND OBJECTIVES: The treatment choice forhigh risk NMIBC is still controversial, and no markers are still availableto guide the urologist in the individualization of therapy. Althoughintravesical chemo and immuno treatments represent the gold standardin adjuvant setting after TURB the percentage of recurrence andprogression under treatment is still high. We here describe the designof a chemosensitivity assay based on the expression of genes involvedin the resistance to standard intravesical regimens.METHODS: 128 patients with high risk NMIBC have beenenrolled, all candidates for TUR-B followed by intravesical treatment.All patients have been evaluated by cystoscopy 3 and 6 months afterTUR-B. One mg of tumoral tissue from each patient was kept formolecular assay subjected to RNA extraction and RT-PCR amplificationswith primers specific for MRP1, MRP2, hENT1, dCK, à5â1 integrin,used to trace a specific chemosensitivity profile to drugs commonlyused in intravesical regimen: anthracyclines, mitomycin-c, gemcitabineand BCG. On the basis of densitometric analysis of the amplificationbands obtained by normalisation with the GAPDH internal controls, weobtained for each patient a chemosensitivity molecular profile. Weconsidered high, intermediate and low sensitivity to mitomycin c, epirubicin,and doxorubicin a ratio MRP/GAPDH 1, 1, 1 respectively.For gemcitabine resistance, we considered sensitivity, intermediatesensitivity and resistance a ratio hENT-dCK/GAPDH 1, 1 and 1respectively. Sensitivity to BCG was evaluated as follows: high, intermediate,low sensitivity in the presence of à5â1/GAPDH 1

A NEW MOLECULAR CHEMOSENSITIVITY TEST TO IMPROVE AND PREDICT EFFICACY OF INTRAVESICAL ADJUVANTTHERAPY IN NMIBC (NON MUSCLE INVASIVE BLADDER CANCER) / DE BERARDINIS, Ettore; Busetto, GIAN MARIA; Antonini, Giovanni; Nicolazzo, Chiara; Arianna, Petracca; Gazzaniga, Paola; Gentile, Vincenzo. - In: THE JOURNAL OF UROLOGY. - ISSN 0022-5347. - STAMPA. - 185(2011), pp. e348-e349. [10.1016/j.juro.2011.02.694]

A NEW MOLECULAR CHEMOSENSITIVITY TEST TO IMPROVE AND PREDICT EFFICACY OF INTRAVESICAL ADJUVANTTHERAPY IN NMIBC (NON MUSCLE INVASIVE BLADDER CANCER)

DE BERARDINIS, Ettore;BUSETTO, GIAN MARIA;ANTONINI, Giovanni;NICOLAZZO , CHIARA;GAZZANIGA, PAOLA;GENTILE, Vincenzo
2011

Abstract

1; 1respectively. We then compared both the molecular profiles of chemosensitivityto the clinical response to the intravesical regimen adopted inthe first 6 months of follow up.RESULTS: This chemosensitivity test was able to predict responseto treatment in 93% of patients. The assay is easy to performwith low costs and rapid time of execution.CONCLUSIONS: Our results are encouraging in the view of anindividualised therapeutic approach, to provide a higher treatmentsuccess rate while sparing patients unnecessary toxicity from drugsthat are not suited for their tumors.; INTRODUCTION AND OBJECTIVES: The treatment choice forhigh risk NMIBC is still controversial, and no markers are still availableto guide the urologist in the individualization of therapy. Althoughintravesical chemo and immuno treatments represent the gold standardin adjuvant setting after TURB the percentage of recurrence andprogression under treatment is still high. We here describe the designof a chemosensitivity assay based on the expression of genes involvedin the resistance to standard intravesical regimens.METHODS: 128 patients with high risk NMIBC have beenenrolled, all candidates for TUR-B followed by intravesical treatment.All patients have been evaluated by cystoscopy 3 and 6 months afterTUR-B. One mg of tumoral tissue from each patient was kept formolecular assay subjected to RNA extraction and RT-PCR amplificationswith primers specific for MRP1, MRP2, hENT1, dCK, à5â1 integrin,used to trace a specific chemosensitivity profile to drugs commonlyused in intravesical regimen: anthracyclines, mitomycin-c, gemcitabineand BCG. On the basis of densitometric analysis of the amplificationbands obtained by normalisation with the GAPDH internal controls, weobtained for each patient a chemosensitivity molecular profile. Weconsidered high, intermediate and low sensitivity to mitomycin c, epirubicin,and doxorubicin a ratio MRP/GAPDH 1, 1, 1 respectively.For gemcitabine resistance, we considered sensitivity, intermediatesensitivity and resistance a ratio hENT-dCK/GAPDH 1, 1 and 1respectively. Sensitivity to BCG was evaluated as follows: high, intermediate,low sensitivity in the presence of à5â1/GAPDH 1
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/478592
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