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Biomedical subjects

G Castello

Publications and source records attributed to G Castello.

84 records · Page 5Linked to original sources

Short-term effects of i.v. injected murine 99MTc-F(ab')2 fragments of an anti-melanoma antibody (HMW-MAA 225.28 S) on haemato-immunological parameters in patients with melanoma.

To evaluate alterations induced by injected murine radiolabelled F(ab')2 fragments of the anti HMW-MAA MoAb 225.28S on the principal haemato-immunological parameters, 32 patients with advanced malignant melanoma were studied. No statistically significant change was found after MoAb administration, but monocytes (3 h after injection) and granular eosinophils (24 h after) were reduced and circulating immune complexes increased (3 h after). No toxic effect or adverse reaction was observed. Therefore, the controlled administration of purified MoAb fragments for diagnostic purposes seems to involve only a very low risk of immediate adverse reactions.

Adolescent↗

Cisplatin, 5-fluorouracil and alpha interferon in non small cell lung carcinoma: a toxicity study.

Data are presented on the general and hematological toxicity of a cisplatin (DDP), 5-fluorouracil (5-FU) and alpha interferon (IFN-alpha) association in patients with stage III B or IV non small cell lung cancer (NSCLC). Twenty patients received DDP (100 mg/mq i.v., day 1) and 5-FU (750 mg/mq/day i.v. continuous infusion, days 1 to 4). In ten of these patients IFN-alpha (3 MU s.c., three times weekly, days 1 to 21) was added. General and hematological toxicity was of a similar degree in both groups. Recombinant granulocyte colony stimulating factor (G-CSF; 5 micrograms/kg b.w. s.c. days 7 to 18) induced a sharp increase in peripheral blood GM-CFU level in patients receiving DDP and 5-FU but not in DDP, 5-FU, IFN-alpha treated patients. The results appear to indicate that IFN-alpha modulation of a DDP, 5-FU combination induces an acceptable degree of toxicity.

Adult↗

Hematotoxicity of 5-fluorouracil-leucovorin in a setting of adjuvant chemotherapy.

Changes of granulocyte macrophage colony forming units (CFU-GM) were assessed in peripheral blood of patients treated with 5-Fluorouracil-Leucovorin adjuvant chemotherapy after removal of colon cancer. The clinical and hematological state of the patients was steady and as far normal as possible. Leucocyte counts did not show significant changes. The mean peripheral blood level of CFU-GM significantly decreased following 5FU-LV infusion, reaching nadir by day 15. These changes of hemopoietic progenitors, not detected by routine hematic cell counts, point to a perturbation of the granulopoietic system by the 5FU-LV association also at doses used in adjuvant chemotherapy.

Aged↗

Hematotoxicity of 5-fluorouracil and alpha-interferon on the human normal hemopoietic progenitors.

The toxic effects of a combination of 5 fluorouracil (5-FU) and interferon alpha on normal human hemopoietic progenitors were assessed in vitro. CFU-GM growth was evaluated following 1 h incubation of bone marrow cell suspension with 5-FU 100 micrograms/ml or IFN-alpha 2a 1000 U/ml, or with both drugs, either simultaneously or sequentially added. IFN-alpha did not show toxic effects on normal human hemopoietic progenitors and the severe toxicity of 5-FU on the latter was not modified by IFN-alpha. These results suggest that the changes observed in vivo of 5-FU toxicity induced by IFN-alpha should be attributed to indirect effects of the latter.

Drug Screening Assays, Antitumor↗

Feasibility and toxicity of combination chemotherapy with ifosfamide, vinorelbine, cisplatin versus ifosfamide, vinorelbine in patients with advanced non small cell lung cancer.

Vinorelbine (VNB) and Ifosfamide (IFO) have recently been proposed for treatment of non small cell lung cancer (NSCLC). The two drugs separately induce response rates in excess of 20% and, when combined, of 32.56%. Cisplatin (DDP) is considered a standard in chemotherapy of NSCLC affected patients. We report data on the feasibility and the toxicity of an IFO, VNB and DDP combination in comparison with IFO, VNB association. Results obtained show that the IFO, VNB, DDP combination has a more severe toxicity profile than the IFO, VNB combination although not to a degree precluding its feasibility. Responses, however, appear somewhat more favorable than in the group treated with the combination IFO, VNB. It is therefore necessary to ascertain if clinical advantages in survival and symptom palliation offered by IFO, VNB, DDP combination outweigh impairment in quality of life due to its significant toxicity.

Aged↗

Toxicity on human hemopoietic progenitors of 2'-2'-difluoro-2'deoxycytidine (gemcitabine).

This study presents results on 2'-2'-difluoro-2'deoxycytidine's (dFdC: gemcitabine) in vitro toxicity on peripheral blood CFU-GM and BFU-E obtained from healthy volunteers. Peripheral blood mononucleated non-adherent cells were cultured according to standard methods with continuous exposure (13 days) to dFdC (4,40 and 400 pmol/L) or following 1 hour's, incubation with increasing drug concentrations (1, 10, 100 mumol/L). The results indicate that dFdC has a marked dose-dependent inhibitory effect on the in vitro growth of peripheral blood hemopoietic progenitors., No significant differences were observed for the growth inhibition induced on CFU-GM and BFU-E. Continuous exposure to dFdC gave an IC50 of 4 pmol/L for both CFU-GM and BFU-E. In four chemotherapy naive patients affected by tumors of different type treated with three standard courses of dFdC the variations in the peripheral blood of hemopoietic progenitor level were determined. Patterns of changes were different, but a marked and sustained decrease of both CFU-GM and BFU-E was observed in one case only. The contrast between the apparently rather mild clinical hemotoxicity of dFdC and its in vitro dramatically potent inhibitory activity on hemopoietic progenitors is discussed.

Antimetabolites, Antineoplastic↗

In vitro toxicity of A 3'-azido-3'-deoxythymidine and hydroxyurea combination on normal myeloid progenitors.

Hydroxyurea (HU) appears to increase 3'-azido-3'-deoxythymidine (AZT) antiretroviral activity and cytotoxicity by inhibiting thymidilate synthesis. The combination of AZT and HU may therefore be of clinical usefulness. We evaluated the in vitro hemotoxicities of different combinations of AZT and HU in comparison with the hemotoxicities exerted by either of the two drugs alone. Peripheral blood granulocyte macrophage committed progenitors (CFU-GM) of healthy donors were selected as targets of hemotoxicity. Both AZT and HU separately had a dose-dependent inhibitory effect on the in vitro growth of normal circulating CFU-GM. The combination of the two drugs induced a statistically significant synergistic cytotoxicity. In fact, addition of HU induced a remarkable reduction of AZT ID50. Thus, future clinical application of AZT, HU combination should take into account the greater hemosuppressive action of the combination in respect to that observed following administration of either drug alone.

Cell Survival↗