摘要:

The pulmonary metastasis of Lewis lung carcinoma was strongly blocked by daily intraperitoneal (i.p.) treatment with 0.5 mg of PCAGeS/kg/day for 7 days after tumor implantation. The metastasis-preventive activity of PCAGeS was markedly reduced when mice were treated with carrageenan, a macrophage blocker. On the other hand, treatment with antiasialo GM1anti-serum did not significantly affect the percentage of inhibition of metastasis by the compound. These results suggest that macrophages rather than natural killer (NK) cells play an important role in the suppression of metastasis by PCAGeS. PCAGeS induced tumoristatic and tumoricidal activities in the peritoneal macrophages of mice by oral administration. The activity of NK cells was also augmented by i.p. treatment with the compound. These results suggest that PCAGeS is a useful substance for preventing pulmonary metastasis.

ISSN:0732-6580    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

Peptidoglycan monomer (dissacharide-pentapeptide, PGM) fromBrevibacterium divaricatumis an immunomodulator and an antitumor agent. As part of our investigation of the antitumor properties of PGM in mice, its potential to stimulate phagocytosis by resident peritoneal macrophages was assessed. Inbred CBA/H/Z Tmice (kept under conventional conditions) were used, and a simple and brief method was developed to evaluate phagocytosis. It consisted of a short (10 min) coincubation of yeast cells (YCs) with peritoneal cells (PCs) and microscopic (phase-contrast) scoring of YC ingestion. Three samples of PGM were injected intravenously into mice (60 mg/kg), and PCs were collected from groups of recipients 8, 16, 24, 48, or 72 h later. All samples temporarily increased phagocytosis, but the extent and duration of the effect varied. Stimulation of phagocytosis also occurred after in vitro exposure (3 h) of PCs to PGM, or to the pentapeptide (PP) part of its molecule. We concluded that PGM could enhance phagocytosis by resident peritoneal macrophages in vivo and in vitro, the PP being the active component in vitro.

ISSN:0732-6580    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

The development of tumor-specific antibodies was studied in a group of cancer patients undergoing active specific immunotherapy with irradiated human allogeneic and autochthonous (autologous) tumor cells injected by the intralymphatic route. Immunoblotting studies on extracts of various established tumor cell cultures and fresh tumor biopsies were performed using sera from these patients. Evaluable tumor regressions were associated with detection of antibodies against human tumor cell antigens of 22,000 daltons (22 kd), 38,000 daltons (38 kd), 43,000 daltons (43 kd), and 70,000 daltons (70 kd). Similar antigens of ∼22, 43, and 70 kd have also been detected in fresh extracts of certain human tumor tissues when tested with antisera from patients responding to immunotherapy. Production of antibodies to these antigens may play a role in tumor regression with active specific immunotherapy. These human regression-associated antigens may, therefore, represent novel agents for cancer immunotherapy.

ISSN:0732-6580    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

We studied the antitumor synergy of human recombinant tumor necrosis factor (TNF) in combination with recombinant interferon-r (IFN-r) both in vitro and in vivo. Synergistic cytotoxic effects were observed in all three of the human tumor cells lines examined. Binding assays of KB human nasopharynx carcinoma cell surface receptors for TNF revealed that IFN-r increased the number of receptors and suggest that this increase may play a key role in the synergism. Furthermore, a remarkable antitumor effect by TNF in combination with IFN-r was observed in nude mice implanted with KB cells. The results thus suggest that TNF and IFN-r in combination may provide the basis for a useful antitumor therapeutic regimen.

ISSN:0732-6580    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

The effect of cyclophosphamide on interleukin-2 (IL-2) therapy was investigated using the intradermal MBT-2 tumor in C3H mice. Human recombinant IL-2 (Biogen) was given intraperitoneally at doses ranging from 5,000 to 30,000 U, three times a day for 5 or II-13 consecutive days beginning on day 10 after tumor implantation. When IL 2 was given alone, mice could not tolerate >5 days of 5,000 U IL 2/injection: Administration of 10,000 and 15,000 U/injection of IL-2 for 5 days resulted in 64% (9 of 14) and 100% (14 of 14) mortality, respectively. Chemotherapeutic agents (cisplatin at 6 mg/kg or JM-8 75 mg/kg) and daily administration of cortisone acetate (75 mg/kg) partially protected mice from IL-2-induced toxic deaths. Coadministration of mannitol showed no protective effect. The combination of IL-2 and CY at 75 or 100 mg/kg, however, dramatically reduced the mortality induced by IL-2 and made it possible to escalate the dose and long-term administration of IL-2. Combination administration of 75 mg/kg CY with 15,000 U/injection of IL-2 for 11–13 days caused tumor regressions and resulted in a 66% (8 of 12) cure rate.

ISSN:0732-6580    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

The effects of adoptive immunotherapy with lymphokine-activated killer (LAK) cells and human recombinant interleukin 2 (IL2), on palpable intradermal (i.d.) bladder tumor were studied. The murine transitional cell carcinoma MBT-2 was used in C3H mice. IL2 was given intraperitoneally at 5,000 U/injection three times a day for 5 consecutive days beginning on day 10. LAK cells were generated in vitro from normal splenocytes: 107-108LAK cells were transferred intravenously on day 10 and, in some experiments, also on day 13. IL2 alone, LAK cells alone (total 8 x 107), and both in combination showed little or no influence on intradermally growing MBT-2 tumors. Cyclophosphamide was also combined with adoptive immunotheraphy (IL2 and LAK). CY (100 mg/kg, i.p. on day 9 or 10) alone was able to suppress i.d. MBT-2 growth significantly. The combination treatment of IL2 and LAK cells with CY caused additional tumor growth suppression in a manner dependent on the total number of LAK cells transferred. The amount of the additional tumor growth suppression was, however, relatively small when compared with CY plus IL2-treated groups. In comparison, experimentally induced 3-day and 10-day pulmonary metastases of MBT-2 cells were treated by the same protocol of IL2 and LAK cells but without CY. IL2 alone reduced the number of gross metastatic nodules in the lung. The addition of LAK cells to the IL2 almost entirely eradicated the 3-day metastatic nodules but was less effective against the 10-day metastases. The data suggest that adoptive immunotherapy with IL2 and LAK cells mediates tumor regression of micrometastases at a selected organ (lung), but is ineffective against the same tumor growing in the skin or in gross metastatic nodules. Host immune suppression by CY was not …

ISSN:0732-6580    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

Toxicity has been observed in mice receiving recombinant human tumor necrosis factor (rhTNF). In the present experiments, several chemicals were used to determine whether they could prevent the lethality of rhTNF without impairing its antitumor activity. Injection of phospholipase A2, cyclooxygenase, and lipoxygenase inhibitors at the same time as rhTNF administration could prevent the lethality of rhTNF, but the antitumor activity was also reduced. Urinastatin and reduced glutathione could prevent the lethality while reducing the activity. In contrast, by pretreatment with O2scavengers, the lethality of rhTNF was markedly reduced without impairment of the antitumor activity of rhTNF. Antihistamines exerted no influence on the lethality of rhTNF. Histopathologic examinations have demonstrated that the capillaries of the tumor tissue show aggregation of platelets and formation of fibrin adherent to the vascular surface after TNF administration. Heparin or protamine revealed no effects against the lethality of rhTNF. These results strongly suggest that the arachidonic cascade is deeply related to the antitumor activity of TNF and its side effects. Pretreatment with O2scavengers, especially bismuth subnitrate, could prevent the lethality of rhTNF without impairing its antitumor activity.

ISSN:0732-6580    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

Monophosphoryl lipid A (MPL), a detoxified form of endotoxin, was evaluated for its ability to elicit cytotoxic factors in the serum of mice pretreated with BCG. BDF, mice were given a priming dose of bacillus Calmette-Guerin (BCG) intravenously (i.v.). Two weeks later, these mice were challenged with MPL i.v. and their serum was tested for cytotoxicity against Lewis lung carcinoma cells growing in culture. A well-tolerated dose of MPL induced substantial serum cytotoxic activity comparable to that found after a toxic dose of endotoxin. The effective dose of MPL for eliciting serum cytotoxicity was 20 times less than the toxic dose of MPL in BCG-primed mice. No serum cytotoxicity was induced by MPL without prior treatment with BCG or in mice exposed to BCG for <10 days. The i.v. route of administration was superior to intraperitoneal, intrapleural, or subcutaneous routes for both BCG priming and induction of serum activity with MPL. Serum manifested TNF-like activity in that it was heat-stable, not species-specific, more effective against tumor than normal cell lines, and more effective against a TNF-sensitive than a TNF-resistant cell line. We conclude that MPL is an effective, well-tolerated biological response modifier that triggers production of cytotoxic factors in serum of mice with an activated reticuloendothelial system.

ISSN:0732-6580    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

To examine the effects of combination therapy with traditional Chinese preparations (Syô-saiko-tô, Zyûzen-taiho-tô orCinnamomumcortex) and OK432 or mitomycin C on the antitumor activities and TNF producibility, an investigation was carried out using mice transplanted with Ehrlich or Meth A tumor cells. Development of the transplanted tumors was strongly inhibited by the combination therapy, and the tumor necrosis factor (TNF) producibility was increased with the combination of a traditional Chinese preparation and OK432. A significant negative correlation was observed between the TNF activities and tumor weight, and there was a positive correlation between the TNF activities and spleen weight in the Ehrlich-bearing DDY mice receiving traditional Chinese preparations or OK432. Marked lymphocytosis, hyperplasia, and hypertrophy of Kupffer's cells in the liver were noted in the tumor-bearing DDY mice receiving traditional Chinese preparations or OK432. In two-step carcinogenesis experiments involving treatment with DMBA and TPA to induce skin papillomas, Zyûzen-taiho-tô appeared to be effective in inhibiting carcinogenesis. These results suggest that the antitumor activities and capacity for TNF production of the preparations are probably due in part to stimulation of the reticuloendothelial system, including macrophages, and induction of a host-mediated antitumor substance like TNF as one of the immunopotentiators.

ISSN:0732-6580    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

An enzyme immunoassay (E1A) for measurement of human serum thymosin β4is described. Antiserum to synthetic thymosin β4, raised in rabbits, is incubated with a standard or serum. The unbound antibody in liquid-phase then binds with solid-phase thymosin β4. The EIA is both sensitive and accurate and is capable of detecting as little as 2.5 ng/ml thymosin β4in serum. No cross-reactivity was observed with common serum proteins or other putative thymic hormones. High-performance liquid chromatography of serum samples reveals a single thymosin β4peak that corresponds to the authentic thymosin β4peak in the standard. Human serum levels range from 3 to 82 ng/ml in 142 healthy adult human volunteers. Newborn cord serum levels of thymosin β4are lower than in adults.

ISSN:0732-6580    

出版商:OVID    

年代:1988

数据来源: OVID