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M Bruzzone

Publications and source records attributed to M Bruzzone.

At least 19 recordsLinked to original sources
PubMed2006

A phase II trial with cisplatin-paclitaxel cytotoxic treatment and concurrent external and endocavitary radiation therapy in locally advanced or recurrent cervical cancer.

BACKGROUND: Five randomized studies have demonstrated a beneficial effect of adding cisplatin-based chemotherapy to radiation therapy in the treatment of cervical carcinoma. In the present phase II study, we evaluated the response and toxicity of cisplatin-Taxol chemotherapy combined with concomitant radiotherapy in patients with locally advanced cervical carcinoma (LACC) and locally recurrent cervical carcinoma (LRCC). PATIENTS AND METHODS: In 2000, this phase II study was initiated with a chemotherapy regimen of cisplatin (75 mg/m(2)) and Taxol (175 mg/m(2)) every 21 days, for four cycles, concomitant with external radiotherapy and high-dose-rate brachytherapy. Pelvic radiotherapy was started 2 weeks after the first chemotherapy cycle, while the first brachytherapy insertion was carried out during the fourth chemotherapy cycle. SCC marker was determined before treatment and after every chemotherapy cycle. RESULTS: All of the 27 patients treated achieved a complete clinical response. Two patients with LACC experienced distant recurrence 22 and 24 months after complete response, respectively, and 1 patient with LRCC had local progression 6 months after the end of radiotherapy. Although generally tolerable, neutropenia grade 3-4 in 4 patients and anemia grade 3 in 2 patients were observed, and 1 patient experienced grade 2 neurotoxicity; toxicity due to radiotherapy was moderate. CONCLUSIONS: Concomitant cisplatin-Taxol chemoradiotherapy seems to be well tolerated, and results, even in this small series, are encouraging.

Adult↗
PubMed2004

Combined treatment with chemotherapy and radiotherapy in high-risk FIGO stage III-IV endometrial cancer patients.

OBJECTIVES: We reviewed our series of very advanced FIGO stage III-IV endometrial cancer patients to assess the efficacy and toxicity of a platinum- and doxorubicin-containing chemotherapy followed by conventional radiotherapy. METHODS: Forty-five patients with advanced FIGO stage III and IV endometrial cancer have been treated, after surgery, with four courses of chemotherapy containing cisplatin 50 mg/m(2), epidoxorubicin 60 mg/m(2) and cytoxan 600 mg/m(2) (day 1 every 21 days) in association with conventional external pelvic radiotherapy (50 Gy, with a 2 Gy daily dose administered with "box technique"). RESULTS: Chemotherapy was well tolerated: WHO grade 4 neutropenia, without fever or other symptoms, has been recorded in six patients (8.8%) at nadir, but no patient required hospitalization or colony-stimulating factors support during chemotherapy. Radiotherapy timing was not delayed by systemic treatment. Toxicities observed during radiation treatment are superimposable to those referred for not pretreated patients. At a median follow-up time of 63 months (range 4-112), 18 patients progressed and 16 patients have died: actuarial 9 years progression-free survival and survival are 30% and 53%, respectively. CONCLUSIONS: The addition of chemotherapy to radiotherapy seems to be an effective and safe way to treat this subset of endometrial cancer patients.

Adult↗
PubMed2001

Advanced ovarian cancer in the elderly: results of consecutive trials with cisplatin-based chemotherapy.

From 1982 through 1996, 547 untreated advanced ovarian cancer patients were entered onto Gruppo Oncologico Nord-Ovest (GONO) consecutive randomized trials including cisplatin-based chemotherapy. End points of analysis included the influence of age on prognosis, toxicity, clinical/surgical response rates, progression-free survival and survival. Of the entire study group, 116 patients were 65 years of age or older at diagnosis. WHO main toxicity (any grade) consisted of: emesis (93% of patients), myelotoxicity (leukopenia in 52%, anemia in 51% and thrombocytopenia in 17% of patients), nephrotoxicity in 13% of patients and neurotoxicity in 10% of patients. No significant difference in toxicity was evident between patients > or = or <65 years. Refusal of CT and early (< or =2 courses) interruption of CT due to toxicity were more frequent in elderly patients (3.4 vs. 1.4%; 3.4 vs. 0.7%, respectively). After a median follow-up of 71 months no difference was observed in survival and progression-free survival between younger and older patients. Cox multiple regression analysis of the entire study population demonstrated that age >65 years per se was not a negative prognostic factor.

Adult↗
PubMed2001

Identification of adenovirus 7h heterogeneity in the E3 region.

Adenovirus genotype 7h was previously reported to be originated from a recombination event between adenovirus genotypes 7p and 3p. Based on those findings, further characterization of other adenovirus 7h strains become important to determine whether all adenovirus 7h strains arose from a single recombinational event. To explore such a possibility, 160 clinical isolates were studied after developing a PCR assay using a primer set designed to amplify the region corresponding to E3-7,7 Kd of adenovirus ADV 7p and E3-9 Kd of adenovirus 3p. The assay was able to differentiate most of the subgenus B strains from adeno 7h with the genotype 3d. The study of several adenovirus 7h clinical isolates revealed the existence of three variants of adeno 7h. One of the variants, 7h3, shows a high degree of similarity with gene E3-9 Kd of ADV 3p, but lacks the corresponding AUG codon. Our results suggest that more than one recombination event may explain the detection of three different types of adenovirus 7h. The genotype variants of adeno 7h were detected in different years, indicating that the recombination events took place independently from each other. The study of the recombination region may allow further understanding of the function of several viral polypeptides in the immune response, and understanding the mechanism involved in virulence associated to adenovirus 7h.

Adenovirus E3 Proteins↗
PubMed2000

Should stimulation therapy for congestive heart failure be combined with defibrillation backup?

Biventricular pacing has been proposed to resynchronize ventricular contraction in patients with congestive heart failure (CHF) and interventricular conduction delay. However, the sudden death rate is still high despite the improvement in cardiac performance. Devices combining biventricular pacing with implantable cardioverter defibrillator (ICD) backup are now under clinical investigation to demonstrate whether they can decrease sudden death. From the first implant of an ICD with biventricular transvenous pacing on August 1998 to April 2000, 96 patients underwent such implants: 67 (70%) received pacemakers alone and 29 (30%), who had class I ICD indications, received combined pacemaker/ICD systems. During a mean follow-up of 283 +/- 170 days, 13 (14%) patients died: 5 of 29 (17%) in the ICD group and 8 of 67 (12%) in the pacemaker group. A total of 15 patients (52%) had ICD shocks and 6 patients (21%) had 113 episodes of ventricular tachyarrhythmias, of which 96 (85%) were converted to sinus rhythm with antitachypacing. The echocardiograms showed a narrowing of the delay between the onset of right and left ventricular outflow from 40 +/- 37 msec to 17 +/- 16 msec (p = 0.03) and a reduction of the mitral regurgitation area from 7 +/- 3.8 cm2 to 5 +/- 4 cm2 (p = 0.04) at 3 months. Functional class improved from 2.8 +/- 0.7 to 1.6 +/- 0.5 (p <0.001) 3 months after implant. Thus, ischemic patients with reduced left ventricular ejection fraction and ventricular tachyarrhythmias seem good candidates for biventricular pacing with ICD backup. The sudden death risk for those with idiopathic dilated cardiomyopathy, however, is difficult to stratify, and the choice of ICD backup has to be considered on the basis of patient safety, as well as of costs.

Aged↗
PubMed2000

Deamidation of RhoA glutamine 63 by the Escherichia coli CNF1 toxin requires a short sequence of the GTPase switch 2 domain.

CNF1, a toxin produced by pathogenic Escherichia coli strains, deamidates the RhoA GTP-binding protein glutamine 63 and impairs RhoGAP-mediated GTP hydrolysis resulting in RhoA permanent activation. Using peptides derived from the RhoA sequence, we found that DTAGQEDYDRL (corresponding to RhoA 59-69 residues) was the minimum RhoA-derived peptide which could be deamidated in vitro by the CNF1 catalytic domain (CNF1-Cter). Site-directed mutagenesis outside the RhoA 59-69 sequence had no influence on glutamine 63 deamidation by CNF1-Cter. RhoA proteins with substitutions L57G, D65G, Y66G, or R70G were not affected in their ability to be deamidated by CNF1-Cter, whereas this was abolished by the R68G substitution. Arginine 68 is part of the DYDRL motif that is strictly conserved in Rho, Rac, and Cdc42 but not in other small GTP-binding proteins consistent with the observation that only Rho, Rac, and Cdc42 can be modified by CNF1.

Amino Acid Sequence↗
PubMed2000

Intraperitoneal versus intravenous cisplatin in combination with intravenous cyclophosphamide and epidoxorubicin in optimally cytoreduced advanced epithelial ovarian cancer: a randomized trial of the Gruppo Oncologico Nord-Ovest.

Intraperitoneal chemotherapy has a strong biological and pharmacological rationale in the treatment of ovarian cancer. From 1989 to 1996 the present study included 113 patients with FIGO stage II-IV ovarian cancer with residual disease less than 2 cm who were randomly allocated to receive 50 mg/m(2) intraperitoneal cisplatin (CDDP) plus 60 mg/m(2) intravenous epidoxorubicin (EPIDOX) and 600 mg/m(2) intravenous cyclophosphamide (CTX) (ipPEC arm) or 50 mg/m(2) intravenous CDDP plus 60 mg/m(2) intravenous EPIDOX and 600 mg/m(2) intravenous CTX (ivPEC arm). Chemotherapy was repeated every 4 weeks for six cycles. Treatment protocol was changed in 22 patients, 2 from the iv arm (who received single-agent carboplatin) and 20 from the ip arm (who were crossed to systemic chemotherapy, ivPEC, or single-agent carboplatin). At the end of chemotherapy, a second-look was performed in 33 of the 54 patients from the ip arm and in 34 of the 57 patients from the systemic arm. The pathologic complete response rate was 41% of all entered patients and 69% of patients submitted to second-look. No significant difference in pathologic response rate as well as in hematologic and nonhematologic toxicities was seen between the two arms. Up to September 1998, 72 patients showed a disease recurrence (33 treated with ipPEC and 39 treated with ivPEC), 55 died (22 ipPEC and 30 ivPEC), and 10 were lost to follow-up (6 ipPEC and 4 ivPEC). Median progression-free survival was 42 and 25 months for ipPEC and ivPEC, respectively (p = 0.13). Median overall survival was 67 and 51 months for ipPEC and ivPEC, respectively (p = 0.14). In conclusion, besides confirming that intraperitoneal chemotherapy is feasible with acceptable toxicity but with poor compliance in community hospitals, this trial showed that intraperitoneal CDDP compared with intravenous CDDP in combination with EPIDOX and CTX obtained a slight (not significant) improvement in progression-free survival and overall survival of optimally cytoreduced advanced ovarian cancer patients.

Adult↗
PubMed1997

Intraperitoneal carboplatin with or without interferon-alpha in advanced ovarian cancer patients with minimal residual disease at second look: a prospective randomized trial of 111 patients. G.O.N.O. Gruppo Oncologic Nord Ovest.

From June 1990 to October 1994, 111 advanced ovarian cancer patients with minimal (less than 2 cm) residual disease after platinum-based front-line chemotherapy and second-look laparotomy entered a cooperative randomized study aimed at evaluating the effectiveness and the toxicity of the addition of interferon-alpha2 to carboplatin, both intraperitoneally (ip) administered. Patients were randomized to receive either 3 courses of ip Carboplatin 400 mg/m2 Day 1 q 28 days (54 pts) (CBDCA) or ip interferon-alpha 25 x 10(6) U Day 1 + ip carboplatin 400 mg/m2 Day 2 q 28 days (57 pts) (CBDCA + IFN). Patients treated with interferon experienced more severe (WHO grade 3-4) leukopenia (28% vs 17.1%) and anemia (14% vs 4.2%). Fever (P = 0.000) and flu-like syndrome (P = 0.02) were significantly more frequent in the combination arm. No difference in gastroenteric, neurologic, or renal toxicity was observed. At a median follow-up time of 13 months (range 1-72) 71 patients showed a disease progression (31 CBDCA, 40 CBDCA + IFN) and 44 patients died (21 CBDCA, 23 CBDCA + IFN). Median progression-free survival was 11 months in the CBDCA group and 10 months in the CBDCA + IFN arm. Median survival was 22 and 29 months in CBDCA and CBDCA + IFN arm, respectively. In conclusion, intraperitoneal interferon-alpha does not seem to improve the results achievable with intraperitoneal carboplatin in this subset of patients, while the toxicity and the costs of the combination are consistently higher than with chemotherapy alone.

Adult↗
PubMed1997

Molecular localization of the Escherichia coli cytotoxic necrotizing factor CNF1 cell-binding and catalytic domains.

Cytotoxic necrotizing factor type 1 (CNF1) induces, in epithelial cells, the development of stress fibres via the GTPase Rho pathway. We showed that CNF1 is able to modify Rho both in vitro and in vivo. Recombinant N-terminal 33kDa (CNF1Nter) and C-terminal 14.8-31.5 kDa (CNF1Cter) regions of the CNF1 protein allowed us to demonstrate that the N-terminal region contains the cell-binding domain of the toxin and that the C-terminal region is responsible for its catalytic activity. CNF1Nter lowered the activity of CNF1 when provided to cells before the toxin whereas CNF1Cter had no effect on CNF1 cell toxicity. CNF1Cter was sufficient to induce a typical CNF1 phenotype when microinjected into African green monkey kidney cells (Vero cells), and was able to modify Rho as previously reported for CNF1. The C-terminal domain lost its catalytic activity when deleted of various subdomains, suggesting a scattered distribution of catalytic-site amino acids. Elucidation of the CNF1 functional organization and analysis of amino acid homologies between CNFs (CNF1, CNF2), Pasteurella multocida toxin (PMT) and dermonecrotic toxin of Bordetella pertussis (DNT) allowed us to postulate that CNFs and DNT act on Rho via the same enzymatic activity located in their C-terminus, and that CNFs and PMT probably bind to analogous cell receptors.

Amino Acid Sequence↗
PubMed1996

High-dose versus low-dose cisplatin in combination with cyclophosphamide and epidoxorubicin in suboptimal ovarian cancer: a randomized study of the Gruppo Oncologico Nord-Ovest.

PURPOSE: The aim of the study was to compare high-versus low-dose cisplatin in combination with cyclophosphamide and epidoxorubicin as primary chemotherapy for suboptimal stage III and IV ovarian cancer. PATIENTS AND METHODS: One hundred forty-five patients were randomized to receive six courses of cisplatin 50 or 100 mg/m2 plus epidoxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2. The two treatment arms were well balanced; all patients had greater than 2 cm and 37.2% had greater than 5 cm of residual disease; 29.6% had stage IV disease. RESULTS: Patients in the high-dose arm received a double dose-intensity and double total dose of cisplatin. The high-dose regimen induced significantly more episodes of leukopenia (47.8% v 32.8%, P = .05), thrombocytopenia (21.7% v 3.2%, P = .003), anemia (37.6% v 12.5%, P = .002), nephrotoxicity (six v one patient), and neurotoxicity (30.4% v 6.3%, P = .002). There were no significant differences in efficacy in terms of clinical response rate (high-dose 57.5% v low-dose 61.1%), pathologic complete response (CR) (9.6% v 18.1%), median survival times (29 v 24 months), and median progression-free survival (18 v 13 months). CONCLUSION: This study shows that doubling the dose-intensity and total dose of cisplatin in combination with epidoxorubicin and cyclophosphamide has significant toxic effects and does not improve clinical outcome in patients with suboptimal ovarian cancer.

Adult↗
PubMed1995

Rhabdomyolytic acute renal failure in cardiac surgery. A clinical case.

OBJECTIVE: Authors describe 1 case of rhabdomyolytic acute renal failure as a complication of Cardiopulmonary bypass. EXPERIMENTAL DESIGN: Case report. SETTING: Department of Cardiac Surgery. INTERVENTIONS: Patient affected by rhabdomyolytic acute renal failure was treated with pharmacological therapy, plasmapheresis and continuous arteriovenous hemofiltration (CAVH). RESULTS: Anuric acute renal failure was diagnosed in 2nd post surgical day; serum myoglobin values was 16000 micrograms/l (normal values in non surgical patients < 88 micrograms/l), creatine phosphokinase serum values was 8790 UI/L (with Mb fraction < 8%). Patient underwent CAVH and two a day sessions of plasmapheresis; hematochemical and hemodynamic parameters improved progressively with resolution of acute renal failure and resumption of the diuresis on the 10th day. The CAVH was suspended on the 11th day and plasmapheresis on the 5th. Rhabdomyolytic syndrome should be correlated to the direct cannulation of the femoral artery for cardiopulmonary bypass and to prolonged time of extracorporeal circulation, with consequent leg ischemia/reperfusion induced injury which occurs during the extracorporeal circulation and continued during postoperative period; contributory causes should be the low cardiac output syndrome and alpha vasoconstrictor effect of high dose continuous intravenous administration of epinephrine. CONCLUSIONS: Rhabdomyolytic acute renal failure is a severe complication of cardiopulmonary bypass; plasmapheresis and continuous arteriovenous hemofiltration seems to be suitable treatments.

Acute Kidney Injury↗
PubMed1994

High-risk early-stage ovarian cancer. Randomized clinical trial comparing cisplatin plus cyclophosphamide versus whole abdominal radiotherapy.

From 1985 to 1989 70 patients with high-risk FIGO Stage I-II ovarian carcinoma entered a randomized trial comparing chemotherapy (CT: cisplatin 50 mg/m2 + cyclophosphamide 600 mg/m2 day 1 every 28 days for 6 courses) versus whole abdominal radiotherapy (WAR) given according to the open-field technique (43.2 Gy/24 fractions to the pelvis and 30.2 Gy to the upper abdomen). Protocol violations occurred in 8 patients randomized to WAR who received CT because of their own and/or physician's decision. Since protocol compliance was poor and accrual low the study was prematurely closed. Treatment-related toxicity for patients receiving CT was mild and tolerable, consisting chiefly of controllable grade 3 emesis (71%). Grade 3-4 diarrhea was experienced by 28% of patients treated with WAR; severe enteritis requiring hospitalization was observed in 2 patients. Late bowel obstruction requiring surgery was observed in 1 patient. At a median follow-up of 60 months, 21 patients died and 23 relapsed. Five-year survival was 71% and 53% (p = .16), while relapse-free survival was 74% and 50% (p = .07) for CT and WAR, respectively. Although no firm conclusion can be drawn from the present study, a short-term CT, including cisplatin, appears a safe treatment in comparison to WAR.

Abdomen↗
PubMed1994

Randomized study comparing chemotherapy plus radiotherapy versus radiotherapy alone in FIGO stage IIB-III cervical carcinoma. GONO (North-West Oncologic Cooperative Group).

Between January 1989 and December 1991, 64 patients with advanced cervical carcinoma FIGO stage IIb-III were randomized to receive radiotherapy (RT) alone or the sequential combination of chemotherapy (CT) and RT. RT consisted of external RT (40 Gy fractionated over 4 weeks)+brachy-therapy (40 Gy to point A)+an additional boost to the parameters (15-20 Gy) in arm RT; CT consisted of cisplatin 60 mg/m2 i.v. day 1 q 15 days administered for 2 cycles before the start of RT and for 4 cycles after the end of radiation treatment in CT+RT arm. Among the 58 evaluable patients objective response rate was as follows: in RT arm, CR in 40.7% of patients, PR in 40.7%, and SD in 18.6%; in CT+RT arm, CR in 42% of patients, PR in 35.5%, and SD in 22.5%. The median duration of response was 12 months (range: 3-38 + months). At a median follow-up of 36 months survival (S) and progression-free survival (PFS) were 83% and 72.4% in RT arm, 72% and 59.3% in CT+RT arm, respectively. No significant difference was observed between the 2 treatment arms, neither in terms of objective response nor in terms of S and PFS. Both treatments were generally well tolerated. In our experience the addition of chemotherapy to standard radiotherapy does not enhance morbidity and does not interfere with the correct delivery of the planned treatment. However, results of this combined modality regimen remain unsatisfactory, since no improvement in pelvic control and survival of patients with advanced cervical carcinoma was observed.

Adult↗
PubMed1994

Therapeutic experience of the North-West Oncology Group (GONO) on ovarian carcinoma.

The North West Oncology Group is a cooperative group that has carried out several clinical trials on the treatment of ovarian carcinoma in the last 10 years. In a randomized study of advanced ovarian carcinoma patients, the combination of cisplatin plus cyclophosphamide (PC) came out as superior to cisplatin plus cyclophosphamide plus doxorubicin in terms of complete clinical and pathological response rates and 8-years progression free survival (PFS). A randomized trial showed that PAC and cyclophosphamide plus doxorubicin plus carboplatin (CAC) were equivalent in terms of objective response (OR) rates, pathologic complete response (pCR) rates, median survival (S) and median PFS. After PAC or CAC therapy, patients with pCR or minimal residual disease were included in a randomized trial comparing abdominopelvic radiotherapy (RT) versus 3 more courses of the chemotherapy they had received before. This study was stopped early because of a clear advantage in S and PFS for chemotherapy arm. Patients with macroscopic residual disease at second-look surgery and patients with progressing or relapsing disease after first line chemotherapy crossed to an alternative analogue: from PAC to carboplatin and from CAC to cisplatin. An OR was obtained in 25% of the patients of the cisplatin arm and in only 9% of the patients of carboplatin arm. Randomized clinical trials analyzing the role of intraperitoneal administration of chemotherapy and the role of biological response modifiers such as interferons in the treatment of patients with advanced epithelial ovarian carcinoma are currently ongoing.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Cerebral metastases secondary to ovarian cancer: still an unusual event.

An incidence of cerebral metastases secondary to epithelial ovarian cancer as high as 11.6% has been reported in small series and related to the prolonged survival of ovarian cancer patients treated with platinum compounds (Hardy, J. R., and Harvey, V. J. Gynecol. Oncol. 33, 296-300, 1989). A review of the histories of 413 ovarian cancer patients, treated from 1981 to 1989 with platinum-based combination chemotherapy according to the protocols of the Gruppo Oncologico Nord Ovest (GONO) (North West Oncology Group), showed that only 9 patients (2.2%) developed clinical evidence of cerebral metastases. Six of 9 patients had FIGO Stage IIIc disease and 1 each with FIGO Stages Ic, IIc, and IV. All these patients had received cisplatin or carboplatin-based combination chemotherapy. Clinical response to initial cytotoxic therapy was as follows: complete response, 3 patients; partial response, 4 patients; stable disease, 1 patient; progressive disease, 1 patient. Cerebral metastases occurred at a median of 19 months (range 3-36) from diagnosis and median survival of patients with central nervous system (CNS) metastasis was 26 months (range 10-81) from diagnosis of primary disease and 8 months (range 1-45) from diagnosis of CNS involvement. The incidence of CNS metastases in our series is similar to that reported in the past and significantly lower than figures reported by the above mentioned paper. On the basis of our data we do not agree with Hardy and Harvey about the relationship possibly existing between prolonged survival and incidence of CNS metastases and, particularly, about the need for prophylactic cranial irradiation.

Aged↗