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Biomedical subjects

A Falcone

Publications and source records attributed to A Falcone.

At least 19 recordsLinked to original sources
PubMed1992

Nodular lesions of the liver in multiple myeloma: a role for cytoadhesion molecules?

Two patients with multiple myeloma and in vivo macroscopic nodular lesions of the liver are presented. The clinical aspects of this very unusual condition are briefly reviewed. In particular, the expression on neoplastic plasma cells of the cytoadhesion molecules CD56 and CD11a, which are involved in the cellular process of recirculation and homing, suggests a possible role for such markers in this atypical localization of the disease.

Aged↗
PubMed1992

ACTH fragments reverse experimental haemorrhagic shock in rats.

Hypovolemic shock was produced in rats by withdrawing about 50% of estimated total blood volume. Following mean arterial pressure stabilization in the range of 25-27 mmHg, the rats were given intravenous ACTH (1-4) (4-9) (4-10) (5-10) (1-10) in comparison with ACTH (1-24). The ACTH fragments, administered within 5 min after shock induction, promptly and dose-dependently improved mean arterial pressure and survival of rats; the ACTH (1-10) showed an activity similar to that of ACTH (1-24) whereas the other fragments were less active.

Adrenocorticotropic Hormone↗
PubMed1990

Benzylacyclouridine reverses azidothymidine-induced marrow suppression without impairment of anti-human immunodeficiency virus activity.

Increased extracellular concentrations of uridine (Urd) have been reported to reduce, in vitro, azidothymidine (AZT)-induced inhibition of human granulocyte-macrophage progenitor cells without impairment of its antihuman immunodeficiency virus (HIV) activity. Because of the clinical toxicities associated with chronic Urd administration, the ability of benzylacyclouridine (BAU) to effect, in vivo, AZT-induced anemia and leukopenia was assessed. This agent inhibits Urd catabolism and, in vivo, increases the plasma concentration of Urd in a dose-dependent manner, without Urd-related toxicity. In mice rendered anemic and leukopenic by the administration of AZT for 28 days in drinking water (1.5 mg/mL), the continued administration of AZT plus daily BAU (300 mg/kg, orally) partially reversed AZT-induced anemia and leukopenia (P less than .05), increased peripheral reticulocytes (to 4.9%, P less than .01), increased cellularity in the marrow, and improved megaloblastosis. When coadministered with AZT from the onset of drug administration, BAU reduced AZT-induced marrow toxicity. In vitro, at a concentration of 100 mumol/L, BAU possesses minimal anti-HIV activity and has no effect on the ability of AZT to reverse the HIV-induced cytopathic effect in MT4 cells. The clinical and biochemical implications of these findings are discussed.

Anemia↗
PubMed1990

Different effect of benzylacyclouridine on the toxic and therapeutic effects of azidothymidine in mice.

It has been reported that in vitro uridine (Urd) can reverse azidothymidine (AZT) cytotoxicity without decreasing anti-human immunodeficiency virus (HIV) activity. Our studies in mice have shown that daily oral doses of benzylacyclouridine (BAU), an inhibitor of Urd breakdown, also reduces AZT hematologic toxicity, presumably by elevating the plasma concentration of Urd. We now extend these murine studies and report the effect of various doses of exogenous Urd, various doses of BAU, or the combination of BAU and Urd, administered daily, on AZT-induced toxicity. In mice receiving concomitant AZT, daily doses of Urd of 1,000 to 2,000 mg/kg increase peripheral reticulocytes and slightly reduce AZT-induced hematologic toxicity. However, the range of effective doses is narrow, and higher doses of Urd (greater than 3,000 mg/kg/d) significantly enhance hematologic toxicity. At its most effective dose, (2,000 mg/kg/d), Urd produces 28% mortality. In contrast, BAU doses up to 300 mg/kg/d reduced AZT-related hematologic toxicity in a dose-dependent manner without mortality. Higher daily doses of BAU and the combination of BAU with low doses of Urd were not more effective. Studies conducted in mice infected with the Rauscher murine leukemia virus (RLV) indicate that BAU does not impair the antiretroviral effect of AZT when administered at doses that reduce AZT-induced anemia and leukopenia. These findings may be significant for the treatment of patients with acquired immunodeficiency syndrome (AIDS) and AIDS-related complex.

Acquired Immunodeficiency Syndrome↗
PubMed1990

5-Fluorouracil enhances azidothymidine cytotoxicity: in vitro, in vivo, and biochemical studies.

Preliminary in vitro studies suggest that the combination of 5-fluorouracil (FUra) and 3'-azido-3'-deoxythymidine (AZT) is more cytotoxic than either agent alone. Therefore, a biochemical and therapeutic evaluation of this combination was initiated. Quantitation of the cytotoxicity of FUra plus AZT against the growth of HCT-8 cells in vitro revealed that 1 microM FUra (approximately 10% inhibitory concentration) increased the cytotoxicity of AZT and decreased its 50% inhibitory concentration by 60%. Similarly, incubating HCT-8 cells in 5 microM AZT (approximately 10% inhibitory concentration) decreased the 50% inhibitory concentration of FUra by over 50%. Biochemical analysis indicated that AZT did not affect FUra-induced inhibition of thymidylate synthase or [3H]-FUra incorporation into nucleic acids. In contrast, incubation in 5 microM FUra increased the incorporation of [3H]-AZT (5 microM) into the nucleic acid fraction of these cells by 52% (P less than 0.05). Therapeutic evaluation of this combination in athymic (nude) mice bearing HCT-8 xenographs revealed that, while weekly FUra (85 mg/kg) or AZT (600 mg/kg) exerts minimal antineoplastic activity (after 4 courses, treatment/control = 0.81 and 0.70, respectively), their combination, at the same doses, inhibited tumor growth by nearly 70% (P less than 0.01 versus FUra alone). FUra-related host toxicity was not increased by the addition of AZT. Higher doses of FUra alone were not more effective than FUra plus AZT. In vivo, AZT did not affect the incorporation of [3H]-FUra into the nucleic acid fraction of various murine tissues, including HCT-8 xenografts. FUra, however, increased [3H]-AZT incorporation into nucleic acids in a tissue-specific manner. In the presence of FUra, the incorporation of [3H]-AZT in spleen, liver, and gut increased 40, 21, and 4%, respectively, while in HCT-8 xenografts [3H]-AZT incorporation increased more than 2-fold. Analysis of the activities of selected enzymes involved in pyrimidine metabolism suggests that this tissue-specific effect may be related to the pyrimidine salvage capacity of these tissues. These findings are described in light of their potential impact on human colon cancer chemotherapy.

Animals↗
PubMed1990

The thyrotropin releasing hormone analogue, RGH 2202, reverses experimental haemorrhagic shock in rats.

Hypovolemic shock was produced in rats by withdrawing about 50% of the estimated total blood volume. Following mean arterial pressure stabilization in the range of 22-23 mm Hg, the rats were given an i.v. bolus injection of L-6-ketopiperidine-2-carbonyl-L-leucyl-L-proline amide (RGH-2202) to be compared with thyrotropin-releasing hormone (TRH). RGH-2202, administered within 5 min following shock induction, dose dependently improved the mean arterial pressure and survival of the rats. The activity of RGH-2202 was superior to that of TRH after i.v. administration; both drugs showed a lower activity after i.m. administration.

Animals↗
PubMed1989

Recombinant alpha-2a interferon plus vinblastine in the treatment of metastatic renal cell carcinoma.

Twenty consecutive metastatic renal cell carcinoma patients were treated with a combination of recombinant alpha-2a interferon (18 X 10(6) U three times weekly) and vinblastine (0.1 mg/kg every 3 weeks). Two patients (10% response rate; 95% confidence limits 1.23-31.7%) achieved partial response and 11 (55%) stable disease. Toxicity was significant but always acceptable: most frequently, patients complained of fever and flu-like symptoms (18 of 19 patients), fatigue (18 of 19 patients), worsening in performance status (15 of 19 patients), and anorexia (15 of 19). The combination of recombinant alpha-2a interferon and vinblastine is active in renal cell carcinoma.

Adult↗
PubMed1989

Phase II trial of recombinant alpha-2b interferon in the treatment of metastatic skin melanoma.

A pilot study was undertaken to evaluate toxicity and activity of recombinant alpha-2b interferon in patients with metastatic malignant melanoma. Interferon was administered at the dosage of 10 x 10(6) IU/m2, 3 times a week i.m. 21 patients entered the study, 17 pretreated with chemotherapy and/or immunotherapy and 6 untreated. We obtained 3 partial responses (14.3%; 95% CL, 3.0-36.3%); 9 patients had stable disease. All patients experienced flue-like symptoms and fever; most fatigue and worsening of performance status. Recombinant interferon alpha-2b at the dosage and schedule used has limited but definite activity in metastatic malignant melanoma; the substantial subjective toxicity must be taken into consideration. Further trials testing recombinant alpha interferon in combination with chemotherapeutic agents, like DTIC, are warranted.

Adult↗
PubMed1989

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↗
PubMed1988

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↗
PubMed1988

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↗
PubMed1988

Regional pharmacokinetic selectivity of intraperitoneal cisplatin in ovarian cancer.

Five patients with intraabdominal ovarian cancer, 4 of whom with concomitant ascites, refractory to cisplatin-containing combination chemotherapy were treated with intraperitoneal cisplatin. Cisplatin, 90 mg/m2, was administered intraperitoneally in 2 liters of warm 0.9% NaCl with a 4-hour dwelling time on day 1 q 21 days. Platinum concentrations in plasma, ascites, ultrafiltrates of plasma and ascites, and urine were assayed by flameless atomic absorption spectrophotometry and determinations were verified by neutron activation analysis. Peak total and ultrafiltrable plasma platinum levels were 1.63 +/- 0.6 and 0.76 +/- 0.3 microgram/ml, respectively. Peritoneal clearance of total platinum (PA) was 21 ml/min whereas body clearance of total platinum was on the average 13.8 times PA, varying from 171 to 429 ml/min; the mean AUC (peritoneum) to AUC (plasma) ratio was 11 +/- 3. In 2 patients control of ascites was obtained, in 1 of these patients prior positive cytology became negative after her first intraperitoneal course. No nephrotoxicity was observed and gastrointestinal toxicity was mild. No catheter-related infections were observed. Intraperitoneal cisplatin therapy is well tolerated, pharmacokinetically rational and may be useful in managing ovarian cancer patients with malignant ascites or minimal residual disease at second-look laparotomy.

Aged↗
PubMed1987

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↗
PubMed1987

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↗
PubMed1987

Metastatic breast cancer: an analysis of prognostic factors in patients treated with aminoglutethimide.

An analysis of 127 women with metastatic breast cancer was carried out. All patients were treated with aminoglutethimide: of 117 evaluable patients, 29 responded, 46 remained stable and 42 progressed. A series of patients' characteristics were analyzed for their prognostic importance for response to this drug. The most important features able to predict response were found to be a previous response to tamoxifen and a long disease-free survival after mastectomy.

Adult↗