ISSN:0732-6580    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

Mice were administered nontoxic monophosphoryl lipid A (MPL) or refined standard bacterial endotoxin (RSE) prior to, simultaneously with, or after infection with Toxoplasma gondii. MPL and RSE given before or with the toxoplasma infection induced significant resistance. Administration of toxic RSE, but not nontoxic MPL, after the establishment of toxoplasma infection significantly shortened the survival time of mice.

ISSN:0732-6580    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

Eighty-nine patients with advanced measurable metastatic renal cell carcinoma were entered into a prospective randomized trial comparing alpha-interferon to gamma-interferon and to the combination. The trial was performed in order to confirm the activity of gamma-interferon and assess the potential clinical synergism. Response rates were 5, 10, and 5%, respectively. The low response rate may have been due to the inability to raise the doses of the interferons to higher levels. Clinical synergy at this dose, route, and schedule of administration in renal cell carcinoma does not exist.

ISSN:0732-6580    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

The immunoglobulin heavy chain derived tetrapeptide, tuftsin (Thr-Lys-Pro-Arg), known for its phagocytosis-stimulating activity, was found to augment the antigen-presenting capacity of macrophages in culture, when applied simultaneously with antigen. Injection of antigens or antigens admixed with tuftsin had no immunogenic effect in vivo. On the other hand, antigen-tuftsin covalent conjugates, injected in aqueous solution intramuscularly or intravenously, significantly augmented antibody production. Studying the mechanism underlying these immunogenic effects, we demonstrate that tuftsin, when applied to macrophages together with, or conjugated to, antigens, signals de novo synthesis of mRNA encoding for interleukin-1 (IL-1), and induces secretion of IL-1 from the cells. We suggest that triggering the immunogenic processes by tuftsin conjugates is a consequence of up-regulation of IL-1 synthesis and secretion.

ISSN:0732-6580    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

The sensitivity of three human colon adenocarcinoma cell lines (LoVo, LS174T, and SW1116) and a human pancreatic adenocarcinoma cell line (Hs766T) to a recombinant ricin A chain-antitransferrin receptor immunotoxin was studied. In addition, the carboxylic ionophore monensin was used in conjunction with the immunotoxin to determine the possibility of increased cytotoxicity without loss of specificity. The immunotoxin, 454A12-rRTA, is composed of the monoclonal antibody 454A12 directed against transferrin receptor and of ricin A chain, which was produced by recombinant DNA techniques. In 18 h dose-response cytotoxicity assays, the median inhibitory dose (ID50) against LoVo, LS174T, and SW1116 was found to be 3 ± 10–10, 3.6 ± 10, and 3.6 ± 10–10M, respectively; in the same assay, the ID50for Hs766T was found to be 4 ± 10–10M. In the presence of monensin, the ID50for the adenocarcinoma cell lines was reduced 9-fold, 28-fold, and 5-fold, respectively. In cytotoxic kinetic assays, 50% of control protein inhibition was reached in immunotoxin-treated LS174T cells 12-fold faster in the presence of monensin than in its absence. Immunotoxin-treated LoVo cells reached 50% inhibition of control protein synthesis fivefold faster in the presence of monensin than in its absence. Furthermore, no toxicity of immunotoxin or potentiation by monensin was observed in either a control cell line (Swiss albino mouse 3T6) treated with specific immunotoxin or with a control immunotoxin assay. These results show the in vitro specificity and selectivity of 454A12-rRTA immunotoxin for human gastrointestinal and pancreatic cancer cell lines.

ISSN:0732-6580    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

The effects of a prostaglandin synthesis inhibitor, indomethacin (Indo), on the growth of Lewis lung carcinoma (LLC) growing as primary subcutaneous tumors in either conventional C57BL/6 mice, T cell deficient nude mice, or natural killer (NK) cell deficient beige mice were studied. In conventional mice, Indo, when continuously administered in the drinking water, consistently and significantly inhibited, in a dose-related fashion, the growth of LLC implanted either subcutaneously in the footpad or in the inguinal region; however, the degree of inhibition of footpad tumor appeared to be greater than that of inguinal tumor. Maximum inhibition was found when Indo was initiated before detectable or measurable tumor developed. If Indo treatment was initiated after tumor growth was evident, then Indo was found to be less effective, although significant inhibition was still observed. Indo also effectively inhibited LLC growing either in the footpad or in the inguinal region of nude or beige mice. The degree of inhibition of both footpad and inguinal tumors in both these mice was comparable to that seen in conventional C57BL/ 6 mice, indicating that mature T cells, NK cells, or soluble products produced only by these cells are not involved in mediating or modulating the inhibitory effects of Indo on LLC growth. Although Indo treatment significantly inhibited LLC growth in vivo, continuous treatment of cultured LLC cells with Indo in vitro did not decrease the growth of cultured cells. These results indicate that the inhibitory effect of Indo in vivo is not the result of a direct inhibitory effect of Indo on these tumor cells. Lastly, this inhibitory effect of Indo in vivo could not be reversed or negated, not even in part, by the simultaneous, daily i.p. administration of 16,16-dimethyl-PGE2. This finding suggests that the inhibitory effect of Indo involves a mechanism other than the inhibition of prostaglandin E2production.

ISSN:0732-6580    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

The antiviral activity of a novel biological response modifier (murabutide MDP derivative) has been investigated in 3-week-old OF1 mice infected with influenza (A/Texas/1/77) virus. In each experimental and control group, 10 mice were infected intranasally with a viral dose producing 50% mortality in 5 days and received murabutide via the subcutaneous or intranasal route at various doses either in a simple or in daily repeated administration. All experiments were done in triplicate. Significant prophylactic or therapeutic effects were observed when murabutide was administered the same day as virus, 4 days or 2 days before virus, and 2 days later. These effects varied with the route of administration and the doses of the compound.

ISSN:0732-6580    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

Eight species of novel recombinant tumor necrosis factor-S (rTNF-SAMgroup) were constructed in which N-terminal amino acid sequences were based on that of TNF-S from THP-1 cells with higher basicity than conventional rTNF-α. Two of this rTNF-SAMgroup, denoted as rTNF-SAM1and rTNF-SAM2, showed more cytocidal activity on A549 lung carcinoma cells and G401 Wilm's tumor cells than did rTNF-α. In addition to these cell lines, rTNF-SAM1revealed strong cytocidal activity on T24 bladder carcinoma cells, which are resistant to rTNF-α. Moreover, possible cachectin activity of rTNF-SAM2seemed to be lower than that of conventional rTNF-α, suggesting that rTNF-SAM2has less side effects. Actually, toxicity as expressed by LD50value of rTNF-SAM2as well as others of the rTNF-SAMgroup was significantly lower than that of conventional rTNF-α. Thus, newly constructed rTNF-SAM1and rTNF-SAM2should be more promising antitumor reagents for clinical use, since they were shown to be superior to conventional rTNF-α both in antitumor effect and in less side effects.

ISSN:0732-6580    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

Enough amounts of tumor necrosis factor (TNF) in mice serum for the therapy were observed by treatment with 100 units of recombinant human TNF-α (rHuTNF-α) followed by administration of OK-432 (a streptococcal preparation). Optimal time interval between rTNF and OK-432 to produce endogenous TNF was 3 h, and priming activity of rTNF persisted for at least 10 h. The same effect was observed using novel human recombinant TNF-SAM2(rHuTNF-SAM2) developed by our group. Production of endogenous TNF using rTNF-α or rTNF-SAM2as a priming reagent was almost equal among various mice strains. Induced TNF in mice serum was completely neutralized by anti-MuTNF antiserum, but not by anti-HuTNF monoclonal antibody. rMuTNF could also induce the priming state; however, the doseresponse kinetics of the priming effect to produce endogenous TNF was different between rHuTNFs and rMuTNF-α, suggesting species specificity among rTNFs used. The therapeutic effect against Meth A and MH134 tumors in mice treated by rHuTNFs in combination with OK-432 was superior to that by single administration of either OK-432 or rHuTNFs or by successive administrations of OK-432. Especially, the antitumor effect against MH134 hepatoma was superior to that of any other treatment using known biological response modifiers so far experienced. These results suggest that such combination antitumor therapy as rTNF together with OK-432 should be applicable to cancer patients.

ISSN:0732-6580    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

We made an immunoconjugate (IC) using the anti-CD5 monoclonal antibody T101 and the chemotherapeutic drug methotrexate. Methotrexate was conjugated to T101 using an active ester intermediate, yielding a drug: antibody molar ratio of 12.4. Although T101 immunoreactivity was not significantly altered by conjugation, the IC did not demonstrate antigen-specific cytotoxicity in vitro. Methotrexate activity, assayed in vitro, decreased approximately 100-fold following conjugation. The IC was tested for in vivo efficacy in athymic mice bearing human T-cell (MOLT 4) xenografts. Experimental arms used in the study included i.p. injections of saline, T101, methotrexate, the IC, and a mixture of T101 and methotrexate. Doses ranged from 500 μg T101 (17.5 μg methotrexate) to 2 mg T101 (70 μg methotrexate). Injections were administered only after palpable tumors were established. In experiments at all doses, totaling 66 animals per arm, injection of the IC significantly inhibited tumor growth, and resulted in more tumor regressions and fewer animal deaths than the other four experimental arms. These data demonstrate that the IC promotes a potential advantage over the use of methotrexate through an increase in the therapeutic index.

ISSN:0732-6580    

出版商:OVID    

年代:1988

数据来源: OVID