EPITHELIAL CELLS COLLECTED BY PROSTATE. MASSAGE: A USEFUL TOOL FOR AN EARLY. DIAGNOSIS OF PROSTATE CANCER? C Festuccia", E ...
THERAPEUTIC FRONTIERS AND MOLECULAR PROGNOSTIC INDICATORS IN ONCOLOGY
IN EXPERIMENTAL WHITE AND BLACK METASTASIS INDUCED BY BRYOSTATIN 1 OR BY TPA·TREATED BL6T MURINE MELANOMA CELLS, DIFFERENT LEVELS OF TGFbl, IL.IO, IFNg AND GELATINASE A HAVE BEEN DETECTED CAM La Porta and R.Comolli Department of Physiology and General Biochemistry, General Pathology, University ofMilan, Italy
Bryostatin 1 and TPA reduce the intracellular melanin level in high metastatic overexpressing nPKCd BL6 (BL6T) cells, thereby inducing white experimental metastasis in syngeneic mice. We evaluate here the possible differences between white and black metastasis induced by both treatments on the TGFb, IFNg, IL-W and gelatinase A levels. Therefore, we have isolated white and black metastasis induced after the injection of bryostatin I or TPA treated cells into the tail vein of syngeneic mice and the level of mRNA has been evaluated by semiquantitative RT-PCR analysis. In order to evaluate the experimental metastatic capacity, the same cells were re-injected into syngeneic mice. Taken together, our findings show significant differences between white and black metastasis in TGFb, IFNg, IL-W e gelatinase A levels. Moreover, when white cells were re-injected into syngeneic mice, they gave big black metastasis. Since it is more difficult to diagnose white metastasis, it seems important that a possible anti-neoplastic drug such as bryostatin 1, induces a white phenotype showing a more aggressive intrinsic potential.
DETECTION OF TELOMERASE ACTIVITY IN EPITHELIAL CELLS COLLECTED BY PROSTATE MASSAGE: A USEFUL TOOL FOR AN EARLY DIAGNOSIS OF PROSTATE CANCER? C Festuccia", E Pascale", A Anqelucci", A Marronaro1, E D'Ambrosio", C Vicentini', and M Boloqna? Departments of 1 Surgery and 2Experimental Medicine, University of L'Aquila; 3Institute of Neurobiology and Molecular Medicine, CNR, Rome, Italy
Telomerase is a ribonucleoprotein complex essential for cell proliferation. Telomerase activity has been detected in many cancers, but not in normal somatic cells. We analyzed telomerase activity in cell extracts of epithelial cells shed by prostatic glands and collected by prostatic massage during routinary clinical digital rectal examination (DRE). Telomerase activity was determined by a modified version of polymerase chain reaction (PCR)-based telomeric repeat amplification protocol (TRAP) assay. We have evaluated 16 patients with prostate cancer (PCa), 10 patients with benign prostatic hyperplasia (BPR) and 4 patients with prostatic intraepithelial neoplasia (PIN). We detected telomerase activity in 88%, 100% and 33% of samples from patients with PCa, PIN and BPR, respectively. One of the telomerase-negative Pea patients had neo-adjuvant therapy before the prostate massage. Patients with a diagnosis of BPR and a telomerase-positive need a close follow-up in order to see whether or not they may have developed cancer. In fact, one of the telomerase-positive patients, initially included in BPR group, had an incidental finding of PCa after trans-urethral resection (TUR). The high rate of telomerase activity in PCa samples'indicates that our method may be an useful tool which could combine the molecular specificity of this new tumor marker with the advantage of a noninvasive biological test in the diagnosis and management of patients with prostate cancer. A larger number of patients and an adequate followup time may confirm these preliminary data.
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MOLECULAR EPIDEMIOLOGY OF BREAST CANCER E Guerra, M Piantelli', B Palombo, and S Alberti Laboratory of Sperimental Oncology, DCBO, Consorzio Mario Negri Sud, Santa Maria Imbaro (Chieti); 'Department of Oncology and Neurosciences, University "G D'Annunzio", Chieti, Italy
Traditional prognostic factors (mainly Iymphnode metastasis and presence for estrogen receptors) represent the main determinants in the choice of adjuvant treatments in patients with breast cancer. Additional prognostic indicators capable to better define the risk profile and strategies for cure of these patients would be extremely useful, particularly at early stages of the disease. These indicators would permit to avoid to treat large numbers of patients with therapies that are considerably toxic and that would be beneficial only in a limited number of patients. They would also allow to rationalize the use of treatments that often are rather expensive, directing them to those subgroups of patients that have a low probability of response to first-line consensus therapies. The development of a tumor derives from alterations of oncogenes or tumor suppressor genes. Thus, molecular alterations of these genes, especially if correlated with specific stages of tumor development, are potential important indicators of prognosis and/or response to therapy. We have undertaken the analysis of histopathological and molecular determinants of tumor progression in post-menopausal breast cancers, in a case-control study. In the course of this study we will analyze 200 cases and 200 controls (tumors with or without relapse at 5 years of follow-up; formalin-fixed paraffin-embedded tumor samples). We will determine IS histochemical markers of proliferation, apoptosis and tumor invasion and 8 molecular parameters indicative of deletion of tumor suppressor genes, rearrangement or amplification and point mutations of oncogenes. A parallel analysis of frozen tumor samples by DNA microarrays and by two-dimentional gel electrophoresis (proteome) will allow a genome-wide analysis of the mRNA and proteins that are expressed by the tumors. The results we will obtain will be evaluated through statistical methods capable to reveal significant aggregations of biological determinants of tumor aggressiveness. The results of these analyses will be utilized to identify breast cancer patients with high risk of relapse, who will be directed to adequate therapies. A pilot study of 8 histochemical parameters in 40 patients has provided indication of significant association of biological aggressiveness with overexpression of proteases and presence of high levels of p53. The accrual of patients from the collaborating centers is ongoing. A reference centre for the molecular and histopathological analysis for the participating general hospitals has been implemented. This collaborative network will be essential to validate the results obtained in a prospective clinical trial.
LUCs VALUES CAN PREDICT THE RESPONSE TO G·CSF OF CANCER PATIENTS TREATED WITH STANDARD DOSE CHEMOTHERAPY A Benoni', F Lanza", G Crepaldi', G Gi1li 2 , D Menon', S Toso1 , D Scapoli', F Nocera 1 , B Marenda 1 , J Scaranaro 1 , G Giutiano", and E Ferrazzi' JRegional
Hospital ofRovigo; 2University of Ferrara, Italy
Large unsteined cells (LUCs) values in peripheral blood and mieloperoxidase index (MPXI) can predict the neutropenia phase of patients treated with standard dose chemotherapy. Regarding the
