摘要:

Herein are reported the results of treating 139 cancer patients with combined immunomodulation that consisted of bacillus Calmette-Guerin, transfer factor, and mixed bacterial vaccine. In addition 28 patients were given infusions of lymphoblastoid lymphocytes. Patients were admitted to this treatment program who either had failed to respond to other modalities, had elected to add immunomodulation to usual therapy, or had refused chemotherapy and/or radiation therapy. The results suggested that combined immunomodulation therapy is well tolerated and safe and that this approach on a prima facie basis had a salutary effect on the courses of a number of the patients treated. The results also illustrate alternative pathways that can be taken by patients and physicians who are not comfortable with protocolized double-blind methods of approaching patients with poor prognosis cancer.

ISSN:0732-6580    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Thirty-three patients with metastatic renal cell carcinoma were treated with recombinant human interferon gamma (rIFNγ) in two sequential, nonrandomized phase II studies. Fifteen patients received rIFNγby daily i.m. injection in doses ranging from 0.25 to 1.0 mg/m2, and 18 patients received it by daily continuous i.v. infusion in doses ranging from 0.01 to 0.05 mg/m2. Partial remissions were achieved by one of 14 (7%) evaluable patients in the i.m. study and in one of 16 in the i.v. study (6%). The incidence of clinical toxicity was similar for both studies. Toxicity was severe in patients receiving rIFNγby the i.m. route at 1.0 mg/m2and by the i.v. route at 0.05 mg/m2. Toxicity includes constitutional symptoms (fatigue, anorexia, weight loss), leukopenia, abnormalities in liver function tests, and hypertriglyceridemia. At the doses and schedules used, rIFNγhad minimal therapeutic activity as a single agent in metastatic renal cell carcinoma.

ISSN:0732-6580    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Oral administration of forphenicinol stimulated the production of lipopolysaccharide (LPS)-induced interferon (IFN) in mice up to 21-fold over control when given more than 10 days before the elicitation. The IFN production in mice sensitized with bacillus Calmette-Guerin (BCG) 14 days before LPS injection was further augmented by forphenicinol given after BCG. In addition to the IFN production, forphenicinol increased production of LPS-induced tumor necrosis factor (TNF) in mice sensitized with BCG, and the dose of LPS required to induce TNF was reduced by the drug. Furthermore, forphenicinol augmented the antitumor effect of BCG and LPS on Meth A fibrosarcoma.

ISSN:0732-6580    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Oral administration of forphenicinol, S-2–(3-hydroxy-4-hydroxymethylphenyl)glycine, inhibited the growth of EL4 lymphoma by both pre- and posttreatment. Although some mice given this drug rejected the tumor, they could not obtain acquired immunity against the tumor. Macrophages taken from normal mice did not inhibit the growth of EL4 cells in vivo (tumor neutralization assay) or in vitro (cytostasis assay). Forphenicinol induced effector activity in such macrophages neither in vitro nor in vivo. Forphenicinol administration to mice bearing EL4 activated macrophages to inhibit the growth of EL4 in vitro and in vivo. Moreover, it stimulated the tumor growth-inhibitory activity of splenocytes in both tumor-free and tumor-bearing mice.

ISSN:0732-6580    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

This study was undertaken in an attempt to evaluate the structure-activity relationship of pyrimidinones. Of 20 pyrimidinones tested, only those with a monohalogen substitution at the ortho- or meta-position of the phenyl moiety of the 2-amino-5-halo-6-phenyl-4(3H)-pyrimidinone and ABPP showed statistically significant synergism with cyclophosphamide (CY) against P388 leukemia. Therefore, ABMFPP, AIMFPP, and ABPP were selected for detailed therapeutic evaluation. The pyrimidinone alone had small but significant activity against B16 melanoma with slightly more than a 25% increase in life-span (ILS); however, when used in combination with CY, ABPP or ABMFPP did not yield an effect greater than treatment with CY alone. Only AIMFPP appeared to produce a more or less additive effect with CY. Although none of these pyrimidinones alone had any significant activity against M5076 tumor, the combination with CY (100 mg/kg) produced a range of 102 to 123% ILS and six to nine of 10 mice per group survived >45 days, whereas the treatment with CY alone yielded only a 48% ILS and none survived >45 days. The synergism of the combination therapy was statistically significant (p < 0.01). The combination used against L1210 leukemia also appeared to be superior to the treatment with CY alone and produced 25 to 50% long-term survivors (>30 days). The significance of these findings is discussed in terms of its clinical implications.

ISSN:0732-6580    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

The in vivo immunorestorative effects of a highly purified protein fraction from human serum—designated SR 270258, prealbumin, or T cell reconstituting factor—was examined in cancer patients following radiation therapy. Sixteen patients with either Stage III head and neck cancer, nonoat cell lung cancer, or esophageal cancer were randomized to either receive (11 patients) or not receive (five patients) subcutaneous injections or SR 270258 at a dose of 2 mg/m2three times per week for a total duration of 1 month. Treated patients were observed frequently for signs of toxicity. Blood was drawn initially and at weekly intervals for measurement of immunologic tests, which included percentage and absolute number of T cells, B cells, and other lymphocyte subpopulations; lymphocyte blastogenic responses to the mitogens phytohemagglutinin, concanavalin A, and pokeweed; and one-way mixed lymphocyte responses. Delayed type hypersensitivity responses to seven recall antigens were also tested. Mean lymphocyte blastogenic responses were significantly suppressed in patients relative to normal (p < 0.05). There were no consistent changes in lymphocyte blastogenic responses, the percentage of lymphocyte subpopulations, or skin test responses in patients receiving SR 270258 versus untreated patients. However, the absolute number of OKT11 positive (E rosette receptor positive) T lymphocytes increased a mean of 52% (406 ± 356 to 617 ± 344/mm3; p = 0.03) in treated patients whereas no change was observed in untreated patients (366 ± 226 to 446 ± 327). Significant increases in the absolute number of OKT4 positive helper cells (158 ± 109 to 221 ± 112; p < 0.05), OKT8 positive suppressor cells (179 ± 186 to 279 ± 184; p < 0.05), and surface immunoglobulin-bearing B cells (49 ± 47 to 155 ± 268; p

ISSN:0732-6580    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

A series of Escherichia coli cloned influenza viral gene products were assayed for their ability to augment human natural cytotoxicity in overnight cultures (18 h) at 37°C. Nylon wool nonadherent peripheral blood mononuclear cells (PBMC) proved responsive to stimulation by a number of cloned viral proteins, the most effective being the nonstructural (NS1) protein (but not NS2 protein) and haemagglutinin and matrix antigen components fused to the N-terminal 81 amino acid sequence of NS1. Furthermore, interferon (IFN) was generated in cultures in which enhanced cytotoxicity was detected and was identified as mostly IFNa (>90%) with <10% IFNγ contamination. The cell type responding to antigen stimulation was present in Percoll fractions enriched for large granular lymphocytes (LGLs); furthermore PBMC activated by NS1 protein fractionated in the low density Percoll fractions (LGL enriched). Using specific anti-IFN antisera, it was shown that IFNa but not IFN7 was responsible for the enhancement of cytotoxicity. Interferon induction and activation of cytotoxicity could not be ascribed to the presence of contaminating bacterial products. These results suggest that a particular NS1 protein configuration is capable of activating human natural killer cells via the induction of IFNa.

ISSN:0732-6580    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

The triggering activities of heterologous fibrinogen and fibrin on endogenous production of tumor necrosis factor (TNF)-like cytotoxic factor in vivo were examined. The triggering activities of fibrinogen or fibrin from four species injected into the peritoneal cavity of C3H/He mice infected i.p. with bacillus Calmette-Guérin (BCG) were tested. Heterologous, but not homologous, fibrinogen and fibrin showed triggering activity. The route of triggering by heterologous fibrinogen to elicit TNF-like activity systemically was studied. Injection of heterologous fibrinogen i.v. into mice infected i.v. with BCG resulted in a 40-fold higher serum TNF-like activity level than after its i.p. injection. The serum TNF-like activity level was maximal 1 h after i.v. injection of heterologous fibrinogen. When heterologous fibrinogen was injected several times i.v. into mice bearing solid-tumors, TNF-like activity was also released into the serum after every injection, although the activity decreased progressively on second and third injections to 10 and 1%, respectively, of that after the first injection. We used heterologous fibrinogens derived from different species for triggering every week to avoid this gradual decrease of TNF-like activity. In this way TNF-like activity was induced as highly as the primary induction. These results showed that TNF-like cytotoxic factor could be produced in vivo locally or systemically by heterologous fibrinogen or fibrin. Thus both agents should be useful as nontoxic triggering agents.

ISSN:0732-6580    

出版商:OVID    

年代:1987

数据来源: OVID

ISSN:0732-6580    

出版商:OVID    

年代:1987

数据来源: OVID