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Biomedical subjects

G Bonadonna

Publications and source records attributed to G Bonadonna.

At least 199 records · Page 11Linked to original sources
PubMed1987

Specific ex-vivo depletion of human bone marrow T lymphocytes by an anti-pan-T cell (CD5) ricin A-chain immunotoxin.

We studied optimal conditions for ex vivo elimination of mature T cells from human bone marrow by T101 immunotoxin (T101-IT) with criteria applicable to graft-versus-host disease (GVHD) prophylaxis prior to allogeneic marrow transplantation. T101-IT consisted of T101 anti-CD5 monoclonal antibody conjugated to purified ricin A-chain toxin. Marrow mononuclear cells isolated by Ficoll-Hypaque or by fractionation with soybean lectin (SBA- cells) were incubated with T101-IT at 37 degrees C with or without ammonium chloride and/or verapamil as potential enhancers of immunotoxin potency. As controls, competitive inhibition studies with unconjugated T101 or irrelevant IgG2a antibody were carried out. Residual T cells were quantified by limiting dilution in phytohemagglutinin (PHA)-interleukin 2 (IL-2) feeder-cell-containing microcultures and hematopoietic progenitors by CFU-GM assay. We demonstrated that T101-IT in the range of 1-100 nM does not affect early total cell viability; that its delayed cytotoxicity is T-cell-specific, greatly enhanced by ammonium chloride, and moderately by verapamil--which also is not synergistic with ammonium chloride; and that 10 nM X 3 fractionated doses (i.e., added at 0, 1.5, and 3 hr of incubation) in the presence of 10 mM ammonium chloride for 4 hr at pH 7.8 consistently induces 2 log T cell depletion. In addition, if the same T101-IT treatment is preceded by fractionation with soybean lectin (i.e., T101-IT treatment of SBA- marrow cells), 3 log T cell depletion is accomplished. We conclude that T101-IT is highly effective in eliminating T cells from donor grafts. However, data presented here indicate that T101-IT should be associated with additional methods, such as soybean lectin fractionation, to ensure more effective ex vivo T cell depletion and acute GVHD prevention.

Ammonium Chloride↗
PubMed1987

Cell kinetics as a prognostic marker in locally advanced breast cancer.

The study analyzes the prognostic implication of cell kinetics on 52 locally advanced breast cancers. All patients were subjected to a multimodal treatment, including primary chemotherapy with doxorubicin and vincristine, surgery, or radiotherapy followed by additional chemotherapy with the same drug regimen. Pretreatment labeling index (LI) is not related to response to primary chemotherapy, whereas it provides information on the course of the disease. In fact, high LI significantly predicts a higher progression rate at the end of the entire combined treatment, a shorter time to disease progression, and a poorer probability of 4-year survival in comparison to low LI. From the present findings, LI appears to be a useful tool to select women with locally advanced breast cancer that would require very aggressive treatment.

Breast Neoplasms↗
PubMed1986

Verapamil inhibits platelet aggregation by a calcium-independent mechanism.

We studied the inhibitory effects of the calcium channel blocker verapamil both on platelet aggregation and intracellular calcium [Ca2+]i in platelets loaded with a fluorescent indicator (quin 2). The inhibitory effects of verapamil on the platelet aggregation response to both thrombin and ionomycin were seen to be clearly dissociated from the verapamil-induced inhibition of the [Ca2+]i increase produced by these agonists. Verapamil-induced inhibition of platelet aggregation was also obtained when using the "calcium-independent" agonist phorbol-myristate acetate (PMA). It may be deduced that a calcium-independent mechanism plays a role in verapamil-induced inhibition of platelet aggregation. We postulate that this mechanism may operate via a protein-kinase C pathway.

Calcium↗
PubMed1986

Salvage treatment of patients suffering relapse after adjuvant CMF chemotherapy.

The efficacy of salvage treatments in 243 patients with operable breast cancer and positive axillary nodes who failed during or after adjuvant chemotherapy with CMF (cyclophosphamide, methotrexate and fluorouracil) was analyzed. Results were compared with those achieved in 100 patients who had relapses after radical mastectomy alone (control group). Salvage treatments consisted primarily of endocrine therapy (castration in premenopausal patients and tamoxifen in postmenopausal women) and chemotherapy (CMF or Adriamycin [doxorubicin] regimens). In 20 patients, however, first salvage treatment consisted of local therapy only (i.e., radiation therapy with or without surgery). In women previously treated with adjuvant CMF, complete plus partial remissions after first salvage treatment were 37% with a median duration of 17 months. In the control group, the response rate was 43% with a median duration of 16 months. The findings also indicated that drug-induced amenorrhea did not lower the objective response to salvage castration. In patients failing with a disease-free interval in excess of 12 months from end of adjuvant CMF, retreatment with the same combination was able to induce remission in 52% of the patients. Current data, derived from prospective controlled studies, confirm that, despite relatively high remission rates, all forms of salvage treatment failed to provide, in unselected cases, long-term control of relapsed breast cancer. Most important, prior adjuvant chemotherapy with CMF did not adversely affect results compared to concomitant controls.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

Prognostic implication of labeling index versus estrogen receptors and tumor size in node-negative breast cancer.

The paper analyzes the relation among tumor size (T), estrogen receptor (ER) status, and labeling index (LI) and their relative merits in predicting the relapse-free (RFS) and overall survival (OS) in 215 node-negative women with primary breast cancer. All patients were subjected to Halsted or modified radical mastectomy; none received postoperative irradiation or systemic adjuvant therapy. The 5-year RFS was 75.3% and OS 89.0%. When singly tested, LI and ER were able to significantly predict RFS and OS. In contrast, T influenced only RFS but not OS. The multivariate analysis showed that, in the presence of the two other variables, only LI retained its prognostic significance both for time to relapse (p = 0.0044) and survival (p = 0.035). From the present findings, LI appears to be a new important prognostic variable in the selection of high risk patients for whom adjuvant systemic therapy should perhaps be part of their primary treatment.

Axilla↗
PubMed1986

BREASTCAN: an expert system for postoperative breast cancer therapy.

An expert system, named BREASTCAN and designed to assist physicians giving postoperative adjuvant chemotherapy for breast cancer, is described. The system is based on frames, each corresponding to one stage of treatment--either a decision-making stage or a therapeutic stage. The system has been designed to allow fast and easy consultation by general practitioners lacking computer knowledge.

Breast Neoplasms↗
PubMed1986

New anthracycline analogs in advanced breast cancer.

To test the activity and toxicity of new anthracycline analogs, a series of Phase II disease-oriented studies were performed in women with advanced breast cancer previously untreated with doxorubicin. All drugs were administered every 3 weeks, and the doses in mg/m2 were as follows: doxorubicin and epirubicin 75 i.v., esorubicin 35 i.v., idarubicin 13 i.v. and 45 p.o. When epirubicin was tested vs doxorubicin, both response rate (13 of 21 or 62% vs 11 of 21 or 52%) and median response duration (11 months vs 13 months) were comparable. In 24 patients, esorubicin yielded complete plus partial response in 21% with a median duration of 15 months. In 27 patients given idarubicin intravenously the response rate was 11% for 4 months and the corresponding findings when the drug was administered orally to 25 women were 24% for 8 months. Acute toxic manifestations were lower following treatment with all three analogs compared to doxorubicin. Cardiac toxicity, as documented by echocardiography, systolic time interval and left ventricular ejection fraction was virtually absent following therapy with epirubicin and idarubicin. After a median cumulative dose of 600 mg/m2 for doxorubicin-treated women there was a significant fall in LVEF compared to basal values. Similar findings were observed after a median cumulative dose of 210 mg/m2 for esorubicin. We conclude that epirubicin is as effective as doxorubicin but comparatively less toxic when administered at the same dose schedule. At the doses and schedules utilized in this study, esorubicin and idarubicin resulted less active in breast cancer.

Adult↗
PubMed1986

Second acute leukemia and other malignancies following treatment for Hodgkin's disease.

The records of 1,329 patients with Hodgkin's disease admitted from 1965 to 1982 were analyzed to assess the relative frequency of second neoplasms. Within a median follow-up of 9.5 years, a total of 68 new cancers were documented. Nineteen cases of acute nonlymphocytic leukemia, 6 cases of non-Hodgkin's lymphomas, and 43 cases with different types of solid tumors were identified. The overall risk of non-Hodgkin's lymphoma was 1.3% +/- 0.6% and of solid tumors was 8.3% +/- 1.5% when basal cell carcinomas were included and 6.7% +/- 1.4% when basal cell carcinomas were excluded. No cases of leukemia were documented in patients treated with radiation therapy only. The 12-year estimate of leukemia by treatment was as follows: chemotherapy only 1.4% +/- 2.3%; radiation plus MOPP (mechlorethamine, vincristine, procarbazine, and prednisone) 10.2% +/- 5.2%; radiation plus ABVD (Adriamycin, bleomycin, vinblastine, and dacarbazine) 0; and radiation plus other drug regimens 4.8% +/- 1.6%. The risk of leukemia was particularly high (15.5% +/- 7.4%) in patients who received salvage MOPP after radiation failure. A positive association was also noted between increasing age and risk of second malignancies, especially leukemia. The incidence of second neoplasms can be markedly decreased by deleting from potentially curative therapy certain drugs such as alkylating agents, procarbazine, and nitrosourea derivatives.

Acute Disease↗
PubMed1986

Alternating non-cross-resistant combination chemotherapy or MOPP in stage IV Hodgkin's disease. A report of 8-year results.

In patients with stage IV Hodgkin's disease mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) was randomly tested against MOPP alternated monthly with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD). All 88 evaluable patients had not received chemotherapy and 25 had had a relapse after primary irradiation. The complete remission rate with MOPP/ABVD was 88.9% (40 of 45 patients), and with MOPP, 74.4% (32 of 43 patients). The 8-year results show that MOPP/ABVD was superior to MOPP in terms of freedom from progression (64.6% compared to 35.9%; p less than 0.005), relapse-free survival (72.6% compared to 45.1%; p less than 0.01), total survival (83.9% compared to 63.9%; p less than 0.06), and survival of complete responders (94.8% compared to 77.1%; p = 0.04). The delivery of MOPP/ABVD was not associated with an increased incidence of major toxicity. The early sequential rotation of two equally effective and non-cross-resistant drug combinations can substantially improve the likelihood of cure in patients with Hodgkin's disease.

Adolescent↗
PubMed1986

CCNU, etoposide, and prednimustine (CEP) in refractory Hodgkin's disease.

Starting in February 1980, 58 patients with Hodgkin's disease refractory to both MOPP and ABVD received as third-line chemotherapy a combination of CCNU or lomustine, etoposide, and prednimustine (CEP). Complete response (CR) was achieved in 40% of cases and partial response (PR) in 14%. The median duration of CR was greater than 15 months, and the median survival of complete responders was longer than 24 months. In addition, CEP alternating with ABVD was given to 21 patients refractory to MOPP chemotherapy. In this series, CR was documented in 67% of patients with a median duration of 24+ months and a median survival of 36+ months. Treatment was generally well tolerated, and all acute side effects were reversible. Present findings indicate that CEP is an effective regimen in patients refractory to MOPP and ABVD.

Antineoplastic Combined Chemotherapy Protocols↗