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6. Clinical and Experimental Projects on Chemotherapy of Bladder Tumours

Author

Pavone-Macaluso, M., Rausa, L., Gebbia, N., Caramia, G., Rizzo, F.P., Arena, E., Tessitore, V., and Vecchioni, M.

Abstract

Our clinical and experimental experience with chemotherapy of bladder tumours is reviewed. The routes of drug administrations, drug dosages and combinations, are presented. Adjuvant radiotherapy and chemoprophylaxis of certain tumours are discussed.S. Afr. Med. J., 48, 631 (1974)

Published
2017

8. Different expression of thymidylate synthase in primary tumour and metastatic nodes in breast cancer patients

Author

Cabibi, D., Calascibetta, A., Martorana, A., Campione, M., Barresi, E., Rausa, L., Aragona, F., Sanguedolce, R., CABIBI D, CALASCIBETTA A, MARTORANA A, CAMPIONE M, BARRESI E, RAUSA L, ARAGONA F, and SANGUEDOLCE R

Subjects
Adult, Ki-67 Antigen, Lymphatic Metastasis, Humans, Breast cancer, thymidylate synthase, Mib-1/Ki-67, metastatic lymph nodes, Breast Neoplasms, Female, Cell Growth Processes, Thymidylate Synthase, Settore MED/08 - Anatomia Patologica, Immunohistochemistry, Neoplasm Staging
Abstract

BACKGROUND: To date an accurate evaluation of predictive markers in breast cancer is mainly conducted at the primary site, although the main goal of the adjuvant therapy is the control of micrometastases. Adjuvant therapy drugs need a high proliferative cell rate to be effective. The proliferating activity can be evaluated by the Ki-67 marker and even by thymidylate synthase (TS), a cell cycle enzyme present in proliferating cells. In this study the TS levels in primary tumours were compared to those of their metastases. PATIENTS AND METHODS: The TS expression and Ki-67 were evaluated by means of immunohistochemistry in 80 primary breast tumours (PTs) and in their matched axillary metastatic lymph-nodes (ALNs). RESULTS: In 16% of patients, malignant cells of involved nodes showed a lower TS expression than the PTs. In the same group, we also found a lower number of Ki-67 immunoreactive cells in lymph node metastases when compared with primary tumours. CONCLUSION: The group of patients with lower TS and Ki-67 expression in lymph node metastatic cells may be less sensitive to 5-fluorouracil and high dose methotrexate requiring them to be treated with other drug combinations.

Published
2007

11. Thymidilate syntetase gene promoter polymorphisms are associated with TSmRNA expressions but not with microsatellite instability in colorectal cancer

Author

Calascibetta, A., Cabibi, D., Martorana, A., Sanguedolce, G., Rausa, L., Feo, S., Dardanoni, G., and Sanguedolce, R.

Subjects
Settore BIO/14 - Farmacologia, Colorectal cancer, thymidylate synthase, pharmacogenomic, microsatellite instability, polymorphism, molecular therapeutic, Settore BIO/11 - Biologia Molecolare, Settore MED/08 - Anatomia Patologica
Published
2004

17. Clodronate in Metastatic Breast Cancer

Author

Rausa L and Meli M

Subjects
Oncology, medicine.medical_specialty, business.industry, Internal medicine, medicine, General Medicine, business, medicine.disease, Metastatic breast cancer
Published
1998
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18. In VitroGeneration of Cytotoxic T Lymphocytes Against HLA-A2.1 -Restricted Peptides Derived from Human Thymidylate Synthase

Author

Correale, P., primary, Sabatino, M., additional, Cusi, M.G., additional, Micheli, L., additional, Nencini, C., additional, Pozzessere, D., additional, Petrioli, R., additional, Aquino, A., additional, Vecchis, L. De, additional, Turriziani, M., additional, Prete, S.P., additional, Sanguedolce, R., additional, Rausa, L., additional, Giorgi, G., additional, and Francini, G., additional

Published
2001
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37. Carboplatin plus epirubicin plus VP-16, concurrent radiotherapy and “adjuvant” surgery for limited small cell lung cancer (SCLC)

Author

Gridelli, C., primary, Maiorino, A., additional, Curcio, C., additional, D'Aprile, M., additional, Ianniello, G., additional, Brancaccio, C., additional, Palmeri, S., additional, Gentile, M., additional, Comella, G., additional, Pedicini, T., additional, Airoma, G., additional, De Placido, S., additional, Giampaglia, F., additional, Ferrante, G., additional, Iacobelli, S., additional, Rausa, L., additional, and Bianco, A.R., additional

Published
1991
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39. Erythromycin reverses the daunomycin resistance of MEL-DRTL cells

Author

Dusonchet, L., primary, Candiloro, V., additional, Crosta, L., additional, Palmeri, S., additional, Sanguedolce, R., additional, Rausa, L., additional, Perricone, R., additional, Tolomeo, M., additional, Musso, M., additional, Di Miceli, F., additional, Luparello, M., additional, Abbadessa, V., additional, Caravello, E., additional, and Cajozzo, A., additional

Published
1990
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46. Lysosomal alterations in heart and liver of mice treated with doxorubicin.

Author

Gebbia, Nicola, Leto, Gaetano, Gagliano, Mauro, Tumminello, Francesca, Rausa, Luciano, Gebbia, N, Leto, G, Gagliano, M, Tumminello, F M, and Rausa, L

Abstract

This study was carried out to evaluate the influence of long-term treatment with doxorubicin (DXR) (4 mg/kg IV for 5 weeks) on heart and liver lysosomes of mice. We evaluated the variations in both total and "sedimentable" enzyme activity of cathepsin D, which is the major endopeptidase of myocites and probably involved in physiologic and pathologic degradation of actomyosin and mitochondria, and that of acid phosphatase, which is more prominent in interstitial cells. Our results show that marked changes occur in both total and sedimentable enzyme activity of cathepsin D in the heart of treated animals and to a lesser extent in the liver. In contrast, no modification of either total or sedimentable acid phosphatase was seen in either organ. The effects we observed are much more marked for cardiac cathepsin D; this is in good agreement with the cardiac specificity of DXR-induced cardiotoxicity with long-term administration and suggests that lysosomes could play a role in the pathogenesis of this phenomenon. [ABSTRACT FROM AUTHOR]

Published
1985
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47. Phase III randomized study of fluorouracil, epirubicin, and cyclophosphamide v fluorouracil, doxorubicin, and cyclophosphamide in advanced breast cancer: an Italian multicentre trial. Italian Multicentre Breast Study with Epirubicin

Author

Ambrosini G, Palazzotto G, Becchi G, Fornasiero A, Fiorentino M, Calabresi F, Viaro D, Grignani F, Farris A, Foggi Cm, Pastorino G, Rausa L, Bonciarelli G, Fila G, Cartei G, Jirillo A, Bumma C, Di Costanzo F, Capodicasa E, Giuseppe Altavilla, Secondo, Giusto M, Adamo, Lopez M, Lacroix F, Sartori S, Speranza Gb, Palmeri S, Gallo L, Di Lauro L, Minotti, Sacchetti G, Spinelli I, Demicheli R, Maurizio Tonato, Marsilio P, Vici P, Buzzi F, Brugia M, d'Aquino S, Papaldo P, Fosser, Blasina B, Puccetti C, Gambi A, Camilluzzi E, Ardia A, Falchi Am, De Micheli P, Marenco G, Natali M, Cusimano Mp, Zingali G, Daniele O, Poggio R, Moro G, Saccani F, Garusi G, Balli M, D'Alessandro N, Schieppati G, Ciambellotti E, Gebbia N, De Maria D, Padalino D, Bonanni F, Di Carlo A, Bruscagnin G, Bertoncelli P, Chiesa G, Tagliagambe A, Intini C, and Folco U

Subjects
Cancer Research, medicine.medical_specialty, Cardiotoxicity, Leukopenia, Cyclophosphamide, Performance status, business.industry, Nausea, Gastroenterology, Oncology, Fluorouracil, Internal medicine, medicine, Doxorubicin, medicine.symptom, business, medicine.drug, Epirubicin
Abstract

From February 1983 to January 1985, 497 patients with advanced breast cancer were randomly allocated to receive either epirubicin or doxorubicin in the following combination chemotherapy regimen: fluorouracil (5-FU) 500 mg/m2 intravenous (IV) on days 1 and 8; epirubicin or doxorubicin 50 mg/m2 IV on day 1; cyclophosphamide 500 mg/m2 IV on day 1 (FEC or FAC). Cycles were repeated every 21 days until progression or to cumulative doses of 700 mg/m2 for epirubicin and 550 mg/m2 for doxorubicin. Dose reductions were applied according to the standard criteria. Activity was evaluated in 443 patients (222 in the FEC arm and 221 in the FAC arm). The two experimental groups were comparable in age, performance status, menopausal status, histology, previous treatments, and site of the disease. The overall response rate (complete response and partial response [CR + PR]) was not significantly different: 53.6% for FEC and 56.5% for FAC. The median time to progression was 273 days for FEC and 314 days for FAC; the median survival time was 591 and 613 days, respectively. Leukopenia, anemia, nausea, and vomiting were significantly lower in patients treated with FEC. As for cardiotoxicity, four cases of congestive heart failure (CHF) were recorded among patients treated with FAC while only one was observed in the FEC group. These results indicate that epirubicin in a combination chemotherapy regimen is as active as doxorubicin and is significantly less toxic.

Published
1988
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48. Thymidylate Synthase Polymorphism and Microsatellite Instability: Association in Colorectal Cancer.

Author

Calascibetta, A., Rausa, L., Gullotti, L., Buettner, R., and Sanguedolce, R.

Subjects
*GENETIC polymorphisms, *MICROSATELLITE repeats, *COLON cancer, *FLUOROURACIL, *ENZYMES
Abstract

5-Fluorouracil(5FU) is the main drug used for the treatment of colorectal cancer(CRC) and Thymidilate Synthase(TS) is its target enzyme. TS gene has regulatory tandemly repeated sequences in its 5′ and 3′untraslated region(5′–3′ UTR). CRC often shows a kind of genomic instability called Microsatellite Instability(MSI) that is associated with TS levels and survival. Our data show that the genotype 2R/2R(homozygosity for 2 tandem repeat sequences in the 5′UTR) is more frequently associated with MSI + and lower TS levels. More over we did not find any significant association between the 2R/3R(heterozygosity for 2 and 3 tandem repeat sequences in the 5′UTR) and 3R/3R(homozygosity for 3 tandem repeat sequences in the 5′ UTR) genotypes with the MSI + and MSI −, while these genotypes were associated with a higher TS expression. As a consequence we can hypothesise that patients bearing CRC with the MSI +, the 2R/2R genotype and with low TS levels could have a better prognosis and they could not be drug resistant. [ABSTRACT FROM AUTHOR]

Published
2004
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49. Cathepsin D: A possible biochemical marker for anthracycline cardiomyopathy

Author

gaetano leto, Tumminello, F. M., Gebbia, N., Farruggia, P., Rausa, L., Leto G., Tumminello F.M., Gebbia N., Farruggia P., and Rausa L.

Subjects
Doxorubicin, Cathepsin D, Cardiotoxity
Abstract

This study was carried out in an attempt to assess the pattern of cathepsin D variations induced by Doxorubicin (DXR) and to clarify the role possibly played by this endopeptidase in the onset of anthracyclines-induced cardiotoxicity. We evaluated the variations in both total and 'sedimentable' enzyme activity of cathepsin D in the heart of mice treated once a week for up to 8 weeks with DXR (4 mg/kg i.v.b.wt.) and sacrificed 12h, 3 and 6 days after 1, 4, 5 and 8 administrations. Our results show that significant but transitory changes in both total and sedimentable activity of cathepsin D occur after each administration and decline after prolonged treatments. These data do not suggest, but do not exclude, a direct involvement of cathepsin D in the onset of DXR-induced cardiotoxicity: these phenomena might in fact be merely secondary to an increased catabolic activity of cathepsin D following an enhanced metabolic turnover of mitochondrial and myofibrillar protein damaged by DXR. This finding seems however quite interesting because cathepsin D variations might represent one of the long looked for biochemical marker of anthracyclines cardiotoxicity.

50. Resistance to Gemcitabine in a Lymphoma Cell Line Resistant to Fas-mediated Apoptosis

Author

Meli, M., Tolomeo, M., D Alessandro, N., Stefania Grimaudo, Notarbartolo, M., Papoff, G., Ruberti, G., Rausa, L., Dusonchet, L., MELI M, TOLOMEO M, D'ALESSANDRO N, GRIMAUDO S, NOTARBARTOLO M, PAPOFF G, RUBERTI G, RAUSA L, and DUSONCHET L

Subjects
Antimetabolites, Antineoplastic, Fas Ligand Protein, Membrane Glycoproteins, Apoptosis, Lymphoma, T-Cell, Caspase Inhibitors, Deoxycytidine, Gemcitabine, Enzyme Activation, Lymphoma, T-Cell, Cell Line Tumor, gemcitabine, Drug Resistance, Neoplasm, Caspases, Cell Line, Tumor, Deoxycytidine Kinase, Humans, fas Receptor
Abstract

BACKGROUND: The T-cell lymphoma cell line HuT78B1, selected for resistance to Fas-mediated apoptosis, resulted unexpectedly resistant to the apoptotic and cytotoxic effects of gemcitabine (dFdC). We investigated whether this resistance was due to the impairment of the Fas/Fas-ligand (FasL) system. MATERIALS AND METHODS: dFdC effects were studied in HuT78B1 and in the parental Fas-sensitive HuT78 cells exposed to inhibitors of the Fas/FasL system. RESULTS: FasL- and Fas-blocking antibodies did not interfere with dFdC-induced apoptosis in HuT78 cells, whereas inhibitors of caspase-8, -9, -1 or -3 had partial inhibitory effects. Notably, in HuT78B1 cells there was a markedly reduced dFdC accumulation notwithstanding a high activity of the activating enzyme deoxycytidine kinase. dFdC accumulation in HuT78 cells was unaffected by a Fas-blocking antibody. CONCLUSION: This is the first time that the selection of a Fas-resistant cell line led to the isolation of a cell clone unable to accumulate the deoxycytidine analog dFdC. Our results show that this alteration is independent from the impairment of the Fas/FasL system.

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