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

ISSN:0732-6580    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Summary:Previous Phase I trials have established the safety of administering thymosin fraction 5 and thymosin alpha 1 to patients with advanced cancer. These same trials also suggested potential immune‐enhancing doses of these agents. In this study, 12 patients with colon cancer were treated with thrice weekly thymosin fraction 5 at a dose of 120 mg/m2, and 10 patients with non‐small‐cell lung cancer received thymosin alpha 1 at 1.2 mg/m2thrice weekly. Five patients with hypernephroma also received one or both agents by a thrice weekly schedule. There were no tumor responses observed in any of these patients, and immune enhancement was neither obtained nor sustained. We conclude that at these doses and schedules, these hormones have very limited, if any, antitumor properties and that they are incapable of producing immune augmentation as defined by the assays used in this study.

ISSN:0732-6580    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Summary:Despite the striking antiproliferative effect of alpha‐interferon (&agr;‐IFN) in hairy cell leukemia, gamma‐interferon (&ggr;‐IFN) does not appear to have such an effect. We have previously demonstrated the induction of synthesis of specific proteins by &agr;‐IFN, both in vitro and in vivo. We have now shown that &ggr;‐IFN induces synthesis of specific proteins, but the pattern differs from that seen after &agr;‐IFN exposure. The prominent 80,000‐dalton protein induced by &agr;‐IFN was not induced by &ggr;‐IFN, and the prominent 62,000‐dalton protein induced by &ggr;‐IFN was only rarely induced by &agr;‐IFN. Two other proteins were induced by both &agr;‐IFN and &ggr;‐IFN. The other proteins induced by &agr;‐IFN were not induced by &ggr;‐IFN. These differences may be related to the different biological response of hairy cells to the two types of IFN. We also showed for both &agr;‐IFN and &ggr;‐IFN that some IFN‐induced proteins are probably transported to the nucleus of the hairy cell, although the majority of proteins induced by both &agr;‐IFN and &ggr;‐IFN were in the cytosol/membrane fraction of the cell. We have therefore demonstrated that &ggr;‐IFN does have a biochemical effect on hairy cells in terms of induction of specific protein synthesis, leading to the inference that hairy cells must possess another receptor at least functionally analogous to the type II IFN receptors on fibroblasts, with which &ggr;‐IFN interacts.

ISSN:0732-6580    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Summary:Gamma‐interferon appears to be a pivotal molecule in the immune system. Recombinant DNA technology has permitted the cloning and expression of the gene for gamma‐interferon (&ggr;‐IFN), leading to an exponential increase in the level of knowledge both in vitro and in vivo. Laboratory evidence suggests a clinical role for &ggr;‐IFN in collagen vascular disease, chronic granulomatous infectious diseases, hematology, and medical oncology. Phase I trials have identified the toxicities; these toxicities are primarily clinical and include fever, fatigue, flu‐like symptoms, and hypotension. Antitumor activity has been noted in the early development of the drug.

ISSN:0732-6580    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Summary:Thirteen patients with metastatic renal cell carcinoma were entered on a Phase I/II trial of recombinant gamma‐interferon (&ggr;‐IFN). Patients (3) were entered on escalating dose levels, and each patient was escalated to the next dose until an individual maximum tolerated treatment dose (MTD) was established. Multiple parameters of biologic response were measured. Patients were studied twice baseline and at frequent intervals after the initial treatment and every treatment until the patient's individual MTD was reached. The MTD for most patients was <75 × 106U/m2. Small, but statistically significant, enhancement of monocyte antibody‐dependent cellular cytotoxicity and mononuclear cell inhibition of MBL‐2 growth were noted in vitro at &ggr;‐IFN concentrations >250 U/ml. Clinically obvious biologic effects were observed: fever, chills, hypotension, and malaise. However, laboratory assays of peripheral blood mononuclear cell natural killer cell activity, tumor (MBL‐2) growth inhibition, antibody‐dependent cellular cytotoxicity, lymphoblastic transformation, T‐cell subsets, and 2′5′‐oligonucleotide synthetase were not altered in vivo.

ISSN:0732-6580    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Summary:Previous studies have shown that peritoneal macrophages from mice chronically infected with Bacillus Calmette‐Guérin (BCG) become highly cytotoxic for tumor targets upon further in vitro triggering with a variety of agents. In the current studies, achievement of this activated state was characterized by the production and release of a cytotoxin, herein termed cytolytic factor (CF), which appeared in the fluid phase. Production/release of CF by the macrophage required transcription, translation, glycosylation, and an intact secretory apparatus, as evident from inhibition by treatment with actinomycin‐D, cycloheximide, tunicamycin, and monensin, respectively, prior to and during triggering with lipopolysaccharide (LPS). CF obtained by culture of BCG‐activated macrophages appeared rapidly in the supernatant after triggering. Using the actinomycin‐D‐treated L‐929 or EMT‐6 targets in a microassay, CF secreted by macrophages cultured in low molecular weight serum components was detected as an ˜150‐kD component on Sephacryl S‐200. CF demonstrated a spectrum of cytotoxic activity against a number of tumor and normal targets in vitro. Its lytic activity appeared equally effective whether the targets were cultured in medium containing fetal calf serum (FCS) or in Neuman‐Tytell medium without serum during the assay. CF was moderately sensitive to treatment with TLCK and TAME; however, its activity in serum and apparent molecular weight distinguish it from a moiety obtained from BCG‐activated murine macrophages and previously described. A rabbit heteroantiserum raised against highly purified necrosin, a product of the murine macrophage cell line J774.1, was extremely effective in neutralizing the biological activity of CF.

ISSN:0732-6580    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Summary:We have attempted to modify the manner in which chemotherapy influences immune function in lung cancer patients by adding the nonsteroidal, antiinflammatory drug (NSAID) piroxicam to a cytotoxic drug treatment regimen. Eighteen previously untreated patients with lung cancer received cytotoxic chemotherapy with mitomycin‐C (10 mg/m2), vinblastine (6 mg/m2), and cis‐platinum (40 mg/m2) (MVP) on day 1 of a 21‐day treatment cycle; 12/18 patients also received piroxicam (20 mg/day) beginning 10 days prior to MVP and persisting throughout the 21‐day treatment cycle. In vitro tests included (a) phytohemagglutinin (PHA) responsiveness in the presence of indomethacin or interleukin‐2 (IL‐2), (b) natural killer cell (NK) function, and (c) PHA‐induced IL‐2 synthesis. In the 6 patients treated with MVP alone, depressed PHA reactivity was found pretherapy, which was augmented by indomethacin, but not by IL‐2; this was associated with impaired production of IL‐2. By days 7‐14, PHA reactivity, IL‐2 responsiveness, and IL‐2 production rebounded to normal. By days 14‐21, PHA reactivity had declined once again in association with increased indomethacin‐regulation and impaired IL‐2 responsiveness and production. In the 12 patients who received MVP plus piroxicam, PHA and IL‐2 assays improved by days 7‐14 and indomethacin‐regulation was normal; moreover, this improvement persisted throughout the 21‐day treatment cycle. Immunological rebound persisted through as many as 3 consecutive 21‐day MVP plus piroxicam treatment cycles in patients who were continuously monitored. In contrast to these results, piroxicam did not alter the way chemotherapy affected NK function. These results demonstrate that the immunomodulatory effects of cytotoxic chemotherapy can be modified or ameliorated by adding an NSAID to the cytotoxic drug treatment regimen; for certain functions, such as mitogen‐stimulated blastogenesis or IL‐2 production, sustained immunological rebound without immunosuppression can be achieved by this maneuver.

ISSN:0732-6580    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Summary:We have shown previously in several mouse tumor systems that multilamellar vesicles (MLV) are an effective delivery system for generation of macrophage‐mediated tumoricidal activity by C‐reactive protein (CRP). Here we show that resealed erythrocyte ghosts (red cell ghosts, RCG) can function in the same manner. CRP associated with red cell ghosts (CRP‐RCG) inhibited established lung metastases of T241 fibrosarcoma in C57B1/6J mice. The degree of inhibition was comparable to that observed with CRP‐MLV. In other experiments, peritoneal exudate cells, obtained from mice pretreated with CRP‐RCG i.p., inhibited growth and pulmonary metastases of T241 tumor in the Winn neutralization assay. Similar results were obtained with MCA‐38 colon carcinoma in the Winn assay. These studies indicate that erythrocytes deserve consideration as another delivery system for biological response modifiers.

ISSN:0732-6580    

出版商:OVID    

年代:1987

数据来源: OVID