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Biomedical subjects

M Bruzzone

Publications and source records attributed to M Bruzzone.

At least 55 records · Page 3Linked to original sources

Evaluation of the ovarian cancer antigen, Ca-125, as a tumor marker.

The presence of the Ca-125 antigen was tested in the serum of 46 patients with ovarian cancer in order to determine the prognostic value of preoperative levels and its usefulness for monitoring the clinical response in longitudinal studies; survival (S) and progression-free survival (PFS) were also evaluated. In our series, the specificity of the assay in normal subjects and in patients with benign gynecological diseases is 99.3 and 73.2% respectively, and the sensitivity is 91.9%. Preoperative Ca-125 levels are not correlated with S and PFS, whereas an advantage in S and PFS is clearly shown for patients in whom the marker level decreases after treatment. Serial determinations of Ca-125 serum levels provide a reliable test to assess response to therapy and to predict disease progression.

Antigens, Tumor-Associated, Carbohydrate↗

Cisplatin and 5-fluorouracil in advanced and recurrent cervical cancer.

Nineteen consecutive patients with advanced or recurrent cervical cancer were treated with cisplatin 20 mg/m2 plus 5-fluorouracil 200 mg/m2 on days 1-5 every 3 weeks. Toxicity was acceptable and manageable, with most patients treated on an outpatient basis. The most important side effect was dose-cumulative neurotoxicity. In 18 evaluable patients a 61% objective response rate (1 complete and 10 partial) was achieved. In recurrent disease the regimen was effective both in irradiated lesions and in non-irradiated ones. Two out of five patients not previously treated with radiotherapy and/or chemotherapy responded to the treatment but tumor regression was insufficient for the disease to be controlled radically by subsequent surgery or radiotherapy. The median duration of response was 11 months (3-23) and the actuarial survival rate after 36 months follow-up was 43.3%.

Adult↗

Carboplatin (JM 8), adriamycin and cyclophosphamide (JAC) in advanced ovarian carcinoma: a pilot study.

Eleven untreated patients with advanced ovarian cancer were studied for tolerance and response to combination treatment with fixed doses of adriamycin (45 mg/m2) and cyclophosphamide (600 mg/m2) + escalating doses of carboplatin. At the first dose level of carboplatin (200 mg/m2), toxicity was acceptable. With carboplatin at 300 mg/m2, severe hematologic toxicity was observed. The dose-limiting toxicity was leukopenia. Although carboplatin was administered without any hydration, no patient experienced renal toxicity. Eight objective responses were observed in 9 clinically evaluable patients. At second look surgery, 3 complete responses and 4 partial responses were documented. Polychemotherapy with JAC (carboplatin, 200 mg/m2, adriamycin, 45 mg/m2, and cyclophosphamide, 600 mg/m2) is administrable with acceptable toxicity.

Aged↗

Moving-strip abdomino-pelvic radiotherapy after cis-platinum-based chemotherapy and second-look operation. A feasibility study in advanced ovarian cancer.

Sixteen FIGO stage IIB-IV ovarian carcinoma patients who completed six to 12 courses of a cisplatinum-based combination chemotherapy and with minimal (less than 2 cm), microscopic, or no residual disease at second-look laparatomy received moving-strip abdomino-pelvic radiotherapy. Radiation treatment was feasible with acceptable toxicity; two patients had to interrupt therapy--one pretreated with 12 PAC courses because of WHO grade III leukopenia and the other because of grade III diarrhea. A third patient required surgery because of intestinal obstruction 1 month after cessation of radiotherapy. In patients with minimal residual disease at second look, the therapeutic value of sequential radiotherapy was unsatisfactory (five of six progressed), while further investigations were warranted in patients with no or microscopic residuum after second-look operation.

Aged↗

[Hematopoietic microenvironment: cellular and extracellular matrix elements].

In bone marrow, cellular stroma together with extracellular matrix (EM) provide an adequate microenvironment for the proliferation and differentiation of hemopoietic progenitor cells. In this article we describe studies on the cell characteristics of a main stromal phenotype, a fibroblast-like cell and its ability to produce in vitro EM components. Comparative studies were performed in fibroblast cultures derived from normal and acute lymphoblastic leukemic (ALL) bone marrow. The grow characteristics of fibroblasts from ALL marrow as well as its capacity to synthetize collagen, fibronectin and GAGs are impaired when compared to fibroblast from normal marrow. Thus, in ALL the impaired production of EM biomolecules by a transient damaged population of stromal cells, may contribute to the development of a defective microenvironment for hemopoiesis.

Bone Marrow Cells↗

Stage I-II melanoma: the value of metastatic work-up.

A total of 116 asymptomatic patients with malignant skin melanoma entered a multiple staging work-up including chest X-ray, multiple nuclear scans and abdominal ultrasonography. All 116 chest X-rays and 68 brain scans performed gave negative findings. Liver scans resulted in 1/66 false-positive findings. Out of 73 bone scans, 5 gave false-positive results. Only 2 out of 66 abdominal ultrasonographies showed abnormal findings and were found to be true-positive on surgical exploration. Due to the low yield in detecting silent metastases, such a multiple staging work-up would not be regarded as a routine staging program.

Adolescent↗

Cisplatin and cyclophosphamide in early epithelial ovarian carcinoma.

Toxicity and efficacy of adjuvant cisplatin-based chemotherapy were assessed in 41 patients with FIGO stage I-II ovarian carcinoma. Chemotherapy consisted of cisplatin 50 mg/m2 and cyclophosphamide 600 mg/m2 administered on a one-day schedule q 28 d for six courses. Inclusion criteria were based on appropriate staging procedures and absence of macroscopic disease after primary surgery; patients with stage IAi G1-G2 or with borderline tumors were excluded from the study. Second look laparotomy was performed 2 months after termination of chemotherapy. At 60 months the actuarial survival is 77.5%. Recurrences were observed in 8 patients; in 1 case relapse was diagnosed at second look laparotomy. Toxicity was acceptable with only 1 treatment drop-out due to reversible neurotoxicity. Our results demonstrate that short-term chemotherapy including cisplatin is a safe and effective regimen and is suitable for administration on a outpatient basis. In our experience second-look laparotomy has limited value for early detection of relapses.

Adult↗

4-Demethoxydaunorubicin (IMI-30) in refractory epithelial ovarian cancer: a pilot study.

Fifteen patients with advanced epithelial ovarian cancer were treated with 4-demethoxydaunorubicin (IMI-30) after platinum failure. A total of 33 courses of IMI-30 15 mg/m2, per os, daily for 3 consecutive days every 3 weeks were performed. Three patients experienced severe hematologic toxicity (WHO grade greater than or equal to 3), while gastroenteric toxicity was acceptable and no cardiotoxicity was observed. One minor response, 4 stabilization of disease and 7 progression were observed in 12 evaluable patients. In conclusion, IMI-30, at this scheduling, is inactive in our small series of heavily pretreated epithelial ovarian cancer patients.

Aged↗

A randomized trial comparing cisplatin plus cyclophosphamide versus cisplatin, doxorubicin, and cyclophosphamide in advanced ovarian cancer.

After primary surgery, 125 patients with epithelial ovarian cancer (International Federation of Gynaecology and Obstetrics [FIGO] 1c + IIb + IIc = 22 patients, FIGO III = 82 patients, FIGO IV = 21 patients) were randomly allocated to receive PC (cisplatin 50 mg/m2 + cyclophosphamide 600 mg/m2 on day 1 every 28 days) (corrected) or PAC (PC + doxorubicin 45 mg/m2). After six cycles, patients clinically disease-free or with resectable residual disease were submitted to second-look surgery. After restaging, patients in surgical complete response (CR) stopped treatment while those responding partially (PR) received six more courses; patients whose disease progressed were excluded from the study. Among patients with measurable disease, the following clinical response rates were observed: PC = 20% CR, 34.3% PR, 14.3% stable disease, and 31.4% progression; PAC = 40.6% CR, 15.6% PR, 12.5% stable disease, and 31.3% progression. In the 75 patients submitted to second look, the results have been the following: PC = 39.5% CR, 36.8% PR, 7.9% stable disease, and 15.8% progression; PAC = 62.2% CR, 18.9% PR, 10.8% stable disease, and 8.1% progression. The difference in surgical complete response in favor of the PAC regimen is significant (P less than .05). Median survival and progression-free survival were 800 and 400 days, respectively, for PAC arm; median survival and progression-free survival were 680 and 380 days, respectively, for PC. These differences are not significant. Probability of survival was affected by FIGO stage, amount of residual disease, histology, performance status, and response at second look, while no influence was observed according to grade of tumor differentiation and age. Our results demonstrate the usefulness of doxorubicin in terms of surgical CR.

Adult↗

Evaluation of the cochleovestibular function in patients treated with carboplatin for ovarian carcinoma.

Carboplatin (JM8), a new cisdiamminodichloroplatin (CDDP) analogue, has exhibited the same antitumor as CDDP. In our pilot study, aiming at optimizing the dosage of this drug in a combination regimen with other chemotherapics, we planned to evaluate the existence of drug related damage on cochleo-vestibular structures. The study was performed on 9 patients suffering from advanced ovarian carcinoma. The results obtained in our study showed that patients undergoing carboplatin chemotherapy do not require an audiometric check-up. In order to assess definitely the existence of vestibular toxicity of this drug, larger studies planned to test JM8 in a high-dosage regimen are desirable.

Aged↗

Clonal analysis of T lymphocytes isolated from ovarian carcinoma ascitic fluid. Phenotypic and functional characterization of T-cell clones capable of lysing autologous carcinoma cells.

T lymphocytes isolated from ascitic fluid of patients with stage III-IV ovarian carcinoma were cloned by means of a microculture system that allows cloning of virtually all peripheral blood human T lymphocytes. Under these experimental conditions, 15% to 42% of ascitic T cells gave rise to clonal progenies that were analyzed for different functional capabilities. Of the clones obtained, 36%-70% had cytolytic activity in a PHA-dependent assay (using P815 as target cells) that allowed detection of cytolytic cells of any specificity. About one-half of the cytolytic clones lysed the NK-sensitive K562 target cells as well. In addition, 30%-50% of the total clones released IL-2 upon stimulation with PHA for 24 hr. In all patients analyzed a variable proportion (11%-56% of all cytolytic clones) had cytolytic activity against autologous tumor cells. Some of these clones have been analyzed in more detail: 18/21 expressed the T4-T8+ phenotype, whereas the remaining 3 were T4+ T8-. Only one out of 6 clones tested lysed allogeneic ovarian carcinoma cells as well, while 5/8 had a definite NK-like activity. Finally, all 8 clones tested were inhibited by anti-T11 and 7/8 by anti-T8 monoclonal antibody.

Antibodies, Monoclonal↗

Cisplatin, methotrexate, and 5-fluorouracil combination chemotherapy for advanced ovarian cancer.

A combination chemotherapy including cisplatin, 25 mg/m2 on Days 1,8; methotrexate, 30 mg/m2 on Day 1; and 5-fluorouracil, 600 mg/m2 on Day 1 has been evaluated in 28 previously untreated and 10 pretreated patients with advanced ovarian cancer after debulking surgery when feasible. The pathological response rates (complete + partial responses) were 69.2 and 50% in untreated and pretreated patients, respectively. Overall 24-month survival and progression-free survival (PFS) are 19.2 and 10.9%, respectively. A significant difference in survival and PFS is evident between patients with less and more than 2 cm residual disease and between responders (CR + PR) versus nonresponders. No renal toxicity was induced and no cycles had to be delayed because of hemathologic toxicity.

Adenocarcinoma↗

Phase II study with high-dose N5-10-methyltetrahydrofolate and 5-fluorouracil in advanced colorectal cancer.

Thirty-eight patients with advanced colorectal adenocarcinoma were treated with the following regimen: N5-10-methyltetrahydrofolate (MTHF) (200 mg/m2/day) and 5-fluorouracil (5-FU) (375 mg/m2/day) given concomitantly, consecutively for 5 days, every 4 weeks, in order to evaluate the potential advantage derived from the biochemical enhancement of cytotoxic activity of 5-FU by high-dose reduced folates. Of 33 evaluable patients (six of whom had received prior 5-FU chemotherapy) three untreated patients achieved a partial response (9.1%) lasting 84, 281 and 401 days; 24 patients (72.7%) had stable disease lasting a median of 150 days (range 60-304 days). The overall toxicity was acceptable: two patients had severe cardiac symptoms. Pharmacokinetics and biochemical studies seem necessary to determine the optimal dosage and timing of 5-FU and folates.

Adenocarcinoma↗

High dose cisplatin after failure of polychemotherapy containing cisplatin in ovarian cancer. Preliminary results.

A substantial percentage of patients with advanced ovarian cancer will progress or relapse after platinum-based front therapies and will require salvage chemotherapy. In order to evaluate feasibility and effectiveness of high dose platinum (HD-CDDP) nine patients with ovarian cancer were treated with HD-CDDP while progressing after conventional doses of the same drug. Cisplatin 40 mg/M2 d. 1----5 q. 28 days, was administered with forced chloruresis for a total of fifteen cycles. Preliminary results show a promising 44.4% response rate with acceptable toxicity: only one patient had to discontinue treatment because of severe combined toxicity including infection, mucositis, shaking tremors, ototoxicity and palmar hyperkeratosis.

Adult↗

Branched-chain amino acid metabolism in chronic renal failure.

Interorgan exchange of branched-chain amino acids (BCAA) in the postabsorptive state was evaluated in 16 patients with chronic renal failure (CRF) and in 20 subjects with normal renal function, by measuring arterial-venous differences of BCAAs across the leg, brain, hepato-splanchnic (HS) bed, and kidney. In CRF, arterial blood levels of valine are significantly reduced, whereas leucine and isoleucine levels are not different from controls; valine and leucine levels are directly related to GFR. In CRF, a significant decrease in the release of valine by the leg is observed; the leucine release tends to be lower; for both these amino acids, leg release is directly related to their arterial levels. Both ratios of valine and leucine release to total amino acid release by the leg are significantly reduced in CRF. Furthermore, in CRF cerebral uptake and fractional extraction of valine and isoleucine are decreased. In normal subjects, valine and leucine are significantly extracted by the HS bed, whereas in CRF the HS uptake of valine and its fractional extraction fall significantly and leucine uptake is unchanged. The kidney releases significant amounts of leucine both in CRF and in controls. In conclusion, in CRF in the postabsorptive state the exchange of BCAAs, mainly valine, is altered rather early at the major sites of production and utilization, and the flux of these amino acids among the organs is decreased. The primary defect is the decreased output by peripheral tissue, which reduces the supply of BCAAs to the brain and HS bed. Regional metabolic disturbances further impair BCAA utilization.

Adult↗