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M Bruzzone

Publications and source records attributed to M Bruzzone.

72 records · Page 4Linked to original sources

[Activity of renal enzymes producing ammonia from glutamine in the absence of phosphate: 2. Effect of phosphate dependent glutaminase inhibition by heating].

UNLABELLED: It is known that heating at 50 degrees C for 10 minutes inhibits phosphate dependent glutaminase (PDG) activity of renal cortex, without any effect on gamma-glutamyl transpeptidase (gamma GT) and its phosphate independent glutaminase (PIG) activity. The effect of heating on PIG and total gamma GT activities was evaluated in renal cortex homogenates of rats both in normal acid-base equilibrium and in chronic metabolic acidosis (CMA). Homogenates were incubated in a medium containing glutamine 2 mM, no phosphate, at pH 7,40. PIG activity was measured as glutamate production and total gamma GT activity as ammonia production. In normal rats PIG activity was unchanged after heating, whereas a significant decrease of total gamma GT activity was observed (p less than 0,01). CMA caused an increase in both PIG and total gamma GT activity (p less than 0,01) and these increased to a further extent after heating. In both normal and acidotic rats the glutamate production/ammonia production ratio rose to about 1. IN CONCLUSION: a) in the experimental setting used for this study PDG activity does not intervene in glutamate and ammonia production from glutamine; b) heating causes an inhibition of gamma GT activities, other than PIG, both in normal and in acidotic rats; c) in CMA heating increases PIG activity of gamma GT.

Ammonia↗

Cerebral and hepatic urea synthesis in patients with chronic renal insufficiency.

Urea production by the liver and the brain was evaluated in patients with chronic renal insufficiency and in subjects with normal renal function by measuring the arterial-venous differences of urea across the hepatosplanchnic bed and the brain. In five out of seven patients with chronic renal insufficiency no urea release into the hepatic veins was observed, whereas a high urea output by the brain was measured in 6 out of 8 patients. In the control group urea was released only into the hepatic veins. These data demonstrate a defect in hepatic urea synthesis and a switch to cerebral ureagenesis in chronic renal insufficiency.

Adult↗

Salvage chemotherapy with paclitaxel in platinum-resistant advanced ovarian cancer patients.

Encouraging results with Paclitaxel are reported in ovarian cancer patients relapsing and progressing after platinum-based chemotherapy; however, the two populations have different probabilities of a response to a second-line treatment. Here we report the results achieved in 39 patients with platinum-refractory ovarian cancer, treated with Paclitaxel 175 mg/qm2 (or 135 mg/m2 if heavily pretreated) using 3-hour intravenous infusion every 3 weeks, in an attempt to verify the activity of this drug in platinum-resistant patients. The toxicity was mild to moderate and primarily hematologic and neurologic. The objective response rate is 12.8% with no complete responses. The response duration was brief and the median survival 6 (range 1-17) months. An accurate cost-benefit balance is necessary before routinely use of Paclitaxel in platinum-refractory patients. Further research is needed to determine the optimal role of Paclitaxel in the whole therapeutic strategy for ovarian cancer.

Aged↗

Paclitaxel plus ifosfamide in advanced ovarian cancer: a multicenter phase II study.

BACKGROUND: While ovarian cancer is one of the most sensitive cancers to cytotoxic drugs, with objective response rates of 60-80% routinely being reported in previously untreated patients, the majority of individuals with advanced disease ultimately relapse. Paclitaxel, a new and novel antimicrotubule agent, has shown activity as a salvage therapy in epithelial ovarian cancer. More importantly, in a prior study, it has been shown to be active in tumors that have displayed resistance to platinum compounds, with a reported response rate of 20%. Ifosfamide has shown activity in the treatment of patients who previously demonstrated clinical resistance to a platinum-cyclophosphamide combination. Recently, a synergistic activity of Taxol combined with ifosfamide has been reported in ovarian cell lines. Based on these data, a phase I/II study of a combination treatment with paclitaxel and ifosfamide was performed. PATIENTS AND METHODS: Thirty-one patients with recurrent ovarian cancer or ovarian cancer refractory to cisplatin (CDDP)-containing regimens were treated with paclitaxel at a dose of 135 mg/m2 on day 1; ifosfamide was administered at 1 g/m2 on days 2 and 3 for the first cycle and 1.5 and 2 g/m2 with the same schedule in cycles 2 and 3, respectively. In the absence of toxicity, the dose of ifosfamide was maintained at 2 g/m2 for the last three cycles. Cytotoxic therapy was repeated every 3 weeks. RESULTS: A 30% overall objective response rate was achieved in the 30 patients assessable for response. Among 21 platinum-resistant patients, 4 partial responses (19%) were observed, while in the 9 platinum-sensitive patients 2 complete responses and 3 partial responses (55%) were observed. Myelosuppression was the predominant toxicity. Leukopenia (WHO grade 3-4) occurred in 10% of patients who received ifosfamide at a dose of 1 g/m2 and in 18% of patients treated with ifosfamide at 1.5 g/m2. CONCLUSION: Our results confirmed a low activity of paclitaxel in platinum-resistant patients. The results of this combination treatment with paclitaxel-ifosfamide in our platinum-sensitive patients support further investigations in a randomized study of the combination regimen against paclitaxel alone or retreatment with organoplatinum compounds.

Aged↗

Clinical stage I and II endometrial carcinoma: multivariate analysis of prognostic factors.

In 221 patients with FIGO stage I and II endometrial carcinoma, the impact on survival of age at diagnosis, menopausal status, FIGO stage, myometrial invasion, tumor grade and histology was evaluated by univariate and multivariate analysis. At a median follow-up of 50 months (range 45-210), 42 patients had died, and therefore overall survival was 81% (179/221). Univariate analysis showed that age, menopausal status and histology did not influence survival, whereas FIGO stage, myometrial invasion and tumor grade were important prognostic factors. Multivariate analysis showed that tumor grade had a significant and independent impact on survival and confirmed that FIGO stage is the most important parameter influencing survival.

Actuarial Analysis↗

Intraperitoneal chemotherapy with carboplatin and interferon alpha in the treatment of relapsed ovarian cancer: a pilot study.

In ovarian cancer patients intraperitoneal chemotherapy confers pharmacokinetic advantages and appears an attractive way to improve the efficacy of certain antineoplastic agents. Intraperitoneal carboplatin and interferon alpha have been separately evaluated in ovarian cancer "with promising results". We report a phase I-II pilot trial of intraperitoneal carboplatin 400 mg/sqm plus interferon alpha 25 x 10(6) U q 28 d in 16 patients (pts) previously treated with intravenous cisplatin based chemotherapy. All the patients had relapsed (11 pts) or refractory (5 pts) disease; residual tumors were less than 2 cm in 10 pts and greater than 2 cm in 6 pts. Local and general toxicities were moderate, with neither WHO grade 4, nor neurotoxicity and ototoxicity. Myelotoxicity was the most frequent side effect. Among 14 evaluable pts, objective responses were observed in 6 pts (42.8%) including 3 pts with pathologically confirmed complete response (21.4%); six more pts presented prolonged disease-free survival. Response occurred in both categories of pts with greater than or less than 2 cm residual disease, also in pts refractory to prior intravenous cisplatin. The proper role of intraperitoneal treatment cannot be exactly defined without large randomized trials designed to compare intraperitoneal to intravenous drug administrations.

Antineoplastic Combined Chemotherapy Protocols↗

CA-125 monitoring in the management of ovarian cancer.

In 100 ovarian cancer patients serum CA-125 was monitored during treatment and follow-up to verify the prognostic value of its pre-surgery marker level and the usefulness of the test for disease monitoring. A low pre-operative CA-125 was not associated with improved survival or progression-free survival. A significant survival advantage was evident for patients in whom the marker had decreased during treatment, compared to patients in whom the antigen remained unchanged or increased. In 40 patients CA-125 was measured before second look laparotomy: the marker was negative in 100% of patients in, pathological complete response and in 53.5% of patients with residual disease at second look. A marker increase was evident in 32 of 41 patients with either progressive or recurrent disease, and in 17 patients the CA-125 increase was documented from 1 to 9 months before clinical evidence of progression. The pre-operative level of CA-125 did not appear to be of prognostic value. However, the monitoring of CA-125 during treatment and follow-up can provide a reliable method of assessing response and prognosis. CA-125 monitoring is particularly useful for early detection of recurrence.

Adult↗

Alkaline phosphatase activity in the serum of patients with rheumatoid arthritis.

Alkaline phosphatase (ALP) activity was determined in the serum of 145 patients with rheumatoid arthritis (RA) and of 56 patients with osteoarthritis (OA). The mean ALP concentration was 226.9 U/L in RA and 168.7 U/L in OA (p less than 0.001). The prevalence of hyperphosphatasemia was 28% in RA vs 7.1% in OA (p less than 0.01). ALP concentrations significantly correlated with the erythrocyte sedimentation rate (p less than 0.05). Eighteen out of 46 (39%) rheumatoid patients in whom ALP isoenzymes determination was performed showed a predominant liver fraction and 10 (22%) a predominant bone fraction. In women, both ALP and its bone isoenzyme correlated with the number of joints involved by RA. During the followup, major changes of the type of predominant ALP isoenzyme were observed.

Adult↗

Serial determination of platinum, protein content and free sulfhydryl levels in plasma of patients treated with cisplatin or carboplatin.

We report here the results of serial determinations of free-sulfhydryl, protein content and platinum levels in plasma of cancer patients following either cisplatin (cis-DDP, 3 patients, 60 mg/m2) or carboplatin (JM-8, 3 patients, 300 mg/m2) i.v. administration. After treatment with cis-DDP, significant platinum binding to plasma components with MW greater than 25 kD was observed; the ratio free-sulfhydryls/protein content decreased during the first two hours, returning to normal values at 24 hours after injection. In contrast, no evidence of platinum binding to plasma components with MW greater than 25 kD was noted after JM-8 i.v. administration, and the ratio free sulfhydryls/protein content did not change significantly after treatment. In vitro experiments show that at a molar ratio cis-DDP:JM-8 1:10, the two compounds bind to low MW thiols with the same kinetics. These data seems to suggest different interactions at the plasma level of these drugs, which may be correlated with their different toxicity.

Antineoplastic Combined Chemotherapy Protocols↗

Non palpable breast lesions: preoperative sonographic localization.

From 1987 to 1992 at our Institute, 253 patients with non palpable breast lesions (NBPL) underwent a surgical excision. Fifty-one lesions (19.7%) were localized by an injection of a sterile 3% charcoal suspension under sonographic guide. The sonographic features of NBPL were classified as follows: positive in one case (2%), doubtful in 31 cases (60%) and negative in 19 cases (38%). According to our data the preoperative sonographic localization is a useful alternative procedure to stereotactis mammography in case of breast masses and/or areas of increased tissue density or distorted breast architecture.

Adult↗