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S Ben-Efraim

Publications and source records attributed to S Ben-Efraim.

At least 73 records · Page 4Linked to original sources
PubMed1984

Melphalan-mediated potentiation of antitumor immune responsiveness of immunosuppressed spleen cells from mice bearing a large MOPC-315 tumor.

Administration of a low dose of L-PAM (0.75 mg/kg) to mice bearing a large SC MOPC-315 tumor and extensive metastases led to the development of augmented antitumor immune potential in their hitherto immunosuppressed spleen cells. Such drug-induced potentiation of antitumor immune responsiveness appeared by day 2 after chemotherapy, and it could not be further enhanced but was actually reduced by depletion of glass-adherent cells, a procedure which is effective in depleting the cells known to have inhibitory activity (i.e., macrophages and metastatic tumor cells). To establish that L-PAM can lead to selective in situ abrogation of the inhibitory effectiveness of the splenic macrophages and metastatic tumor cells, we demonstrated that incubation of immunosuppressed tumor-bearer spleen cells with a low concentration of L-PAM in vitro also resulted in augmented antitumor immune potential that could not be further augmented by depletion of glass-adherent cells. L-PAM-mediated enhancement of the antitumor immune potential of immunosuppressed tumor bearer spleen cells was due at least in part to the effects of the drug on the splenic metastatic tumor cells. Isolated tumor cells treated with a low concentration of L-PAM were not only devoid of inhibitory activity for the primary in vitro antitumor immune response by normal spleen cells, but actually manifested a strong immunostimulatory capacity. Thus, L-PAM given at a low dose enhances the development of potent antitumor immunity which brings about the eradication of a large tumorigenic load that remains after the drug has been cleared from the circulation.

Animals↗
PubMed1984

In vitro effects of 4-hydroperoxycyclophosphamide on concanavalin A-induced human suppressor T cells.

Treatment in vitro of human peripheral blood lymphocytes (PBL) with ConA induced the generation of suppressor cells which inhibited T cell blastogenic response to ConA and of allogeneic response in the mixed lymphocyte reaction (MLR). Treatment of PBL with 4-hydroperoxycyclophosphamide (4-HPCy) before incubation with ConA markedly decreased the generation of suppressor cells by ConA. The effect of 4-HPCy on generation of suppressor cells was more pronounced in the test of ConA stimulation than in the MLR. Treatment with 4-HPCy had no effect on suppressor cells already induced as shown by incubation of PBL with 4-HPCy after incubation with ConA.

Cells, Cultured↗
PubMed1984

Effects of the methanol extract residue (MER) tubercle bacillus fraction on the production of antibodies in vitro. II. Effects on macrophage and lymphocyte populations.

The effect of the methanol extract residue (MER) fraction of BCG tubercle bacilli on the generation of primary antibody responsiveness in vitro to sheep red blood cells (SRBC) was ascertained in cell reconstitution experiments, employing enriched populations of mouse macrophages and of T and B lymphocytes. In each of the antibody generation cultures one or another of the cell fractions had been exposed to MER, either by treatment of the donor animals or by preincubation with the agent for 48 hr in vitro. In some experiments, supernatants of MER-preincubated cells were employed in place of the cells. Macrophages and T cells that had been exposed to MER in vivo or in vitro and their supernatants demonstrated a markedly greater effect than nonexposed cells in the generation of direct specific plaque-forming cells (PFC) upon antigenic stimulation of the cultures with SRBC. In contrast, PFC production was not stimulated in B-lymphocyte populations that had been in contact with the agent.

Adjuvants, Immunologic↗
PubMed1984

Synergistic effect of N-acetyl-D-glucosamine (NAG) on mitogenic, antigenic and allogeneic stimulation of normal human lymphocytes.

The effect of N-acetyl-D-glucosamine (NAG) on in vitro stimulated human peripheral blood lymphocytes was investigated. NAG was added to lymphocyte cultures stimulated by the mitogen PHA, the antigen PPD or to one-way-stimulated mixed lymphocyte cultures from unrelated donors. The results indicate that NAG (1-2 micrograms/ml) in appropriate experimental conditions has an enhancing effect on DNA and protein synthesis induced by PHA, PPD and allogeneic cells. Addition of NAG (1-2 micrograms/ml) to unstimulated lymphocyte cultures had no effect on DNA or protein synthesis.

Acetylglucosamine↗
PubMed1984

Prevention and treatment of L1210 mouse leukemia by immunization with xenogenized tumor cells combined with immunostimulation by the P40 fraction of C. granulosum and chemotherapy.

The effect on L1210 leukemia in mice of immunostimulation, in combination or not with chemotherapy with either daunorubicin or mitomycin, was studied. Immunostimulation with the immunomodulator P40 isolated from C. granulosum, together with xenogenized syngeneic tumor cells (GA-L1210-Tet: L1210 tumor cells inactivated with glutaraldehyde and coupled with tetanus toxoid), on days -14 and -7 before and days 2 and 9 after tumor inoculation, resulted in significant increase of the mean survival time as compared to control group with or without chemotherapy. Administration of P40 or P40 + GA-L1210-Tet cells, before or before and after inoculation of L1210 cells partly inactivated in vitro with antineoplastic agents, leads to a marked prolongation of mean survival time and to inhibition of ascitic tumor growth in a high percentage of mice. About 50% of the mice treated with P40 + GA-L1210-Tet cells and surviving the first challenge were resistant to rechallenge, providing that P40 + cells were reinjected before the second challenge, whereas all mice treated with P40 alone and surviving the first inoculation, were susceptible to rechallenge. The major conclusion is that treatments of combining chemotherapy, active immunization and nonspecific immunostimulation in the applied sequence are more effective than single treatments for control of L1210 mouse leukemia.

Adjuvants, Immunologic↗
PubMed1983

Increase in the effectiveness of melphalan therapy with progression of MOPC-315 plasmacytoma tumor growth.

Following inoculation with 1 X 10(6) MOPC-315 tumor cells, a single injection of a very low dose of melphalan (L-PAM, L-phenylalanine mustard), 0.75 mg/kg, cured most of the mice bearing a day 11 large primary tumor (20 mm) and metastases, but failed to cure mice bearing a day 4 nonpalpable tumor. Treatment of mice bearing a nonpalpable tumor with the very low dose of drug compromised the ability of the mice to respond effectively to the same low dose of drug when the tumor became large (day 12). However, a nonpalpable tumor could be eradicated by treatment of tumor bearers with a low dose of L-PAM, if it was present concomitantly with a large tumor on the contralateral side. A high dose of L-PAM, 15 mg/kg, cured mice bearing either a nonpalpable or a large tumor. The eradication of the tumor induced by the high dose of L-PAM appeared to be due solely to the tumoricidal effect of the drug. On the other hand, the eradication of the tumor by the low dose of L-PAM also required the participation of antitumor immunity of the host, since subsequent injection of antithymocyte serum abrogated the curative effect of the drug in most mice. Mice cured by a high dose of L-PAM were not resistant to subsequent lethal tumor challenge. In contrast, mice cured by the low dose of L-PAM were able to reject a tumor challenge of 300 times the minimal lethal tumor dose. The results obtained with L-PAM therapy are similar to the results that we had previously reported with cyclophosphamide therapy. Thus, the timing of therapy with a low dose of drug for mice bearing a MOPC-315 tumor is critical for successful therapy. Moreover, the selection of a low dose rather than a high dose of drug to eradicate a large tumor offers the advantage that it results in long-lasting potent antitumor immunity as a consequence of the participation of host antitumor immunity in the eradication of the tumor.

Animals↗
PubMed1982

[Prevention and therapy of L1210 leukemia in mice, using inactivated and grafted tumor cells, in association with the immunomodulator P40, and Antineoplastic Agents (author's transl)].

The effect on L1210 in Mice of an immunostimulation with P40 fraction isolated from C. granulosum and inactivated L1210 cells coupled with tetanus toxoid, in combination or not with chemotherapy with either daunorubicin or mitomycin, has been looked for using various modalities. Cells partly inactivated by action of the drugs in vitro have also been used for grafting the Mice. The strongest inhibition of tumour growth was observed when the following treatment sequence was applied: Immunostimulation, tumor grafting, chemotherapy, immunostimulation. The significance of the reported results for the treatment of Human neoplasia is discussed.

Adjuvants, Immunologic↗
PubMed1982

Differential inhibition of contact sensitivity by suppressor T cells and suppressor factor induced by combined treatment with dinitrobenzenesulphonate and dinitrofluorobenzene.

Suppressor T cells acting on the efferent phase (Ts-eff) of dinitrofluorobenzene-contact sensitivity (DNFB-CS) were induced in BALB/c mice by injection of dinitrobenzenesulphonate (DNBSO3) and subsequent painting (sensitization) with DNFB. Ts-eff cells released a suppressor factor, antigen and strain specific, which was active in vivo in sensitized recipients. Administration of DNBSO3 alone generated suppressor T cells, which acted only on the afferent phase (Ts-aff). Suppressor T cells could not be detected in mice painted with DNFB and desensitized later by injection of DNBSO3.

Animals↗
PubMed1981

[Protective effect of P40 fraction of C. granulosum against leukemia L1210 in mice].

Administration of glutaraldehyde treated L1210 leukemia cells, either alone or coupled with tetanus toxoid by means of glutaraldehyde as well as L1210 cells inactivated by mitomycin, did not induce appreciable protection against a tumorigenic dose of L1210 cells. On the other hand, injection of P40 fraction of C. granulosum induced non-specific resistance to L1210 leukemia and increased the efficiency of specific immunization by either glutaraldehyde treated L1210 cells or cells coupled with tetanus toxoid. Injection of Freund's complete adjuvant resulted in increase of rate of mortality after challenge with L1210 cells.

Adjuvants, Immunologic↗
PubMed1980

Immunocompetence, immunosuppression, and human breast cancer. II. Further evidence of initial immune impairment by integrated assessment effect of nodal involvement (N) and of primary tumor size (T).

Comprehensive immune function by integrated score was assessed in 158 operable, 55 inoperable, and 52 metastatic breast cancer patients relative to 107 healthy controls. The score was derived from in vivo response to PPD and DNCB and in vitro lymphocyte stimulation by PPD and PHA. Proportion of E-RFC was significantly lower in patients than in controls but was not found to correlate directly with the above functional criteria. Fifty-one percent of the patients with early, operable tumors were shown to be at least partially immunosuppressed by integrated score achievement vs. 11% of controls. This proportion rises to 68% of inoperable and 89% of metastatic patients. Quantitative analysis by graded response revealed an additional, significant degree of immune impairment in the respective patient groups by all testing parameters. Depression of immune function in operable patients was not related to age nor influenced by surgery. Immunocompetence of patients with mammary dysplasia did not differ from controls. Increasing size of primary tumor (T) was not found to be matched by progressive degree of immunosuppression, excepting that associated with large T4 tumors. Patients with lymph node involvement (N+) were not significantly immunologically inferior to those without (N0) where the larger operable T2-3) tumors are concerned. In the smallest, T1 tumors, nodal involvement (N+) is accompanied by remarkable immunosuppression relative to T1N0 cases. This finding suggests a pre-existing immune defect inherent in T1N+ patients. It supports the hypothesis that the immunosuppression associated with early breast cancer is primary, patient related. Secondary tumor-induced depression of immune response characterizes advanced and metastatic human breast cancer.

Adult↗
PubMed1980

Immunocompetence, immunosuppression, and human breast cancer. III. Prognostic significance of initial level of immunocompetence in early and advanced disease.

The prognostic significance of immunocompetence determined at diagnosis was analyzed in 158 operable breast cancer patients followed for 3--6 years, in terms of disease recurrence and of length of disease-free period (DFP) and in 52 patients with metastatic disease in terms of length of survival. In vitro lymphocyte stimulation by PPD and PHA were of higher predictive value with respect to probability of disease recurrence than in vivo cutaneous reactivity to PPD and DNCB. Conversely, length of DFP and of survival were found to correlate better with in vivo than within vitro parameters. Absolute number of peripheral blood lymphocytes (PBL) and percent of E-rosette-forming cells (E-RFC) proved devoid of prognostic value. Prognostic separation was best brought out upon analysis by integrated score of immunocompetence, comprising the four functional parameters. Probability of disease recurrence was 0.43 for all operable patients, as calculated by actuarial method 48 months postoperatively; it was 0.26 for optimal and 0.61 for suboptimal responders (P less than 0.0001). Separate analysis of Stage 1 (N0) and Stage II (N+) patients revealed prognostic segregation within each stage: probability of recurrence in Stage I was 0.06 for optimal vs. 0.41 for suboptimal responders (P less than 0.001) and in Stage II it was 0.45 vs. 0.79, respectively (P less than 0.01). These findings may prove valuable for a more selective patient allocation for post-mastectomy adjuvant therapy. Length of DFP was found inversely proportional to initial immunocompetence, with a mean of 23.5 months for good responders and 12.8 months for poor responders (P less than 0.01). Length of survival of metastatic patients was found to correlate with initial (pretreatment) levels of immunocompetence, mean survival being 29.5 months for those with preserved immune function and 12.3 months for the immunosuppressed (P less than 0.001). It was concluded that initial immunocompetence, determined by parameters of cell-mediated immunity, shows strong prognostic association with the subsequently observed course of human breast cancer.

Adult↗