Journal of biological response modifiers最新文献

{"title":"Activation of rat pulmonary lavage cells by intratracheal administration of polyinosinic-polycytidilic acid.","authors":"R A Weiss,&nbsp;P C Meunier,&nbsp;A Kelley,&nbsp;A Klinkner,&nbsp;A M Badger,&nbsp;P J Bugelski","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Systemic administration of biologic response modifiers (BRMs) is often limited by serious adverse effects. Local delivery of a BRM may provide a means to avoid systemic side effects while enhancing host defense. To test this hypothesis, the effects of intratracheal administration of the interferon inducer polyinosinic-polycytidilic acid (Poly-I:C) were examined. We demonstrated that intratracheal administration of Poly-I:C in rats results in alterations in pulmonary lavage cell number, population distribution, and function, suggestive of cellular activation. Following intratracheal instillation of 15, 75, or 150 mg of Poly-I:C, we observed a dose-dependent increase in Fc receptor-mediated phagocytosis, a dose-independent tumoricidal activity directed against xenogeneic P815 murine mastocytoma target cells, and a dose-independent decrease in superoxide anion (O2-) generation. With the exception of O2- generation, these functions returned to normal control levels by 7 days after a single dose of Poly-I:C. Thus, localized administration of Poly-I:C enhanced the host defense capability of pulmonary lavage cells, providing a rationale for compartmentalized immunoprophylaxis in the lung.</p>","PeriodicalId":15063,"journal":{"name":"Journal of biological response modifiers","volume":"9 4","pages":"411-9"},"PeriodicalIF":0.0,"publicationDate":"1990-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13321905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of combinations of interferon-beta ser and interferon-gamma on interferon-inducible proteins and on the cell cycle.","authors":"J H Schiller,&nbsp;M A Horisberger,&nbsp;G Bittner,&nbsp;J M Carlin,&nbsp;B Storer,&nbsp;G I Byrne,&nbsp;J K Willson,&nbsp;E C Borden","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>SKCO 1 human colon carcinoma cells have been shown to be synergistically inhibited in their growth by the combinations of alpha-interferon (IFN-alpha) or beta-interferon (IFN-beta ser) and gamma-interferon (IFN-gamma). To determine if a correlation could be established between this synergistic antiproliferative effect and a synergistic induction in IFN-inducible proteins, or a unique perturbation in the cell cycle, we studied the effects of IFN-beta ser and IFN-gamma, alone and in combination, on 2',5'-oligoadenylate (2-5A) synthetase, indoleamine-2,3-dioxygenase (IDO), a human analogue of the murine Mx protein (p78), and the phases of cell cycle. 2-5A synthetase was maximally induced after a 24-h exposure to both IFN-beta and IFN-gamma. A synergistic enhancement of 2-5A synthetase activity was observed only with low concentrations of each IFN (0.05 ng/ml). IDO activity was induced by IFN-gamma and the combination of IFN-beta ser and IFN-gamma, but not IFN-beta ser alone. The differences in IDO activity between IFN-gamma and the combination, however, were not statistically significant. The p78 protein was induced in a dose-dependent manner by IFN-alpha and IFN-beta ser. IFN-gamma enhanced the expression of p78 induction by IFN-alpha or IFN-beta ser, even at concentrations of IFN-gamma that did not induce the protein when administered as a single agent. The combination of IFN-alpha and IFN-beta ser, which results in an antagonistic antiproliferative effect, also resulted in an antagonistic induction of p78. No changes in the cell cycle were observed following exposure to IFN-beta ser, IFN-gamma, or the combination, and treatment with IFN-gamma did not inhibit the accumulation of cells in G2M caused by colchicine. Thus, the synergistic antiproliferative effect produced by IFN-beta ser and IFN-gamma in SKCO 1 cells could not be correlated with a synergistic enhancement in 2-5A synthetase or IDO activity, or with a perturbation in the cell cycle. In contrast, the combination of IFN-gamma and IFN-alpha or IFN-beta ser synergistically enhanced the expression of p78 protein in these cells.</p>","PeriodicalId":15063,"journal":{"name":"Journal of biological response modifiers","volume":"9 4","pages":"368-77"},"PeriodicalIF":0.0,"publicationDate":"1990-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13541540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tumor necrosis factor-mediated biological activities involve a G-protein-dependent mechanism.","authors":"C Q Earl,&nbsp;J M Stadel,&nbsp;M A Anzano","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The guanine nucleotide binding protein (G-protein) dependency of several of the activities of tumor necrosis factor (TNF), including cytotoxicity, inhibition of lipoprotein lipase activity, blockade of 3T3-L1 differentiation, and receptor binding were examined. TNF induced killing of the TNF-sensitive cell line L929S (ED50 = 30 pM), but had little to no effect on the TNF-resistant cell line L929R (ED50 = 5,300 pM). TNF-induced cytotoxicity in L929S was antagonized in a dose-dependent manner by pertussis toxin (sevenfold increase in ED50). However, TNF-induced cytotoxicity in L929R cells was only minimally affected by pretreatment with a high dose (50 ng/ml) of pertussis toxin (1.5-fold increase in ED50). Parallel biochemical investigations revealed that inhibition was accompanied by toxin-induced ADP ribosylation of a Gi alpha-like subunit in L929 and 3T3-L1 cell membranes. Pertussis toxin also significantly reduced TNF-induced inhibition of lipoprotein lipase activity in 3T3-L1 adipocytes and TNF blockade of 3T3-L1 preadipocyte differentiation. However, pertussis toxin pretreatment of L929S, L929R, and 3T3-L1 cell cultures had little to no effect on TNF receptor binding. These data indicate that several TNF-induced biological activities in the L929 and 3T3-L1 cell lines are partially dependent upon a pertussis toxin-sensitive G-protein.</p>","PeriodicalId":15063,"journal":{"name":"Journal of biological response modifiers","volume":"9 4","pages":"361-7"},"PeriodicalIF":0.0,"publicationDate":"1990-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13321904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of recombinant interleukin-1 alpha, recombinant interleukin-2, recombinant interferon-beta, and recombinant tumor necrosis factor on subcutaneously implanted adenocarcinoma 755 and Lewis lung carcinoma.","authors":"M Iigo,&nbsp;K Nishikata,&nbsp;A Hoshi","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The antitumor activity of recombinant human interleukin-1 alpha (rHIL-1 alpha), recombinant human tumor necrosis factor, and recombinant murine interferon-beta (rIFN-beta) was augmented by concomitant administration of recombinant human interleukin-2 (rHIL-2) in the treatment of adenocarcinoma 755. Especially when a divided dose (two doses/day) of rHIL-1 alpha or rIFN-beta was combined with a divided dose of rHIL-2, the antitumor effect was markedly potentiated. However, only a marginal effect was seen by combination of rHIL-1 alpha and/or rIFN-beta and rHIL-2 against Lewis lung carcinoma, a tumor that is resistant to cytokines.</p>","PeriodicalId":15063,"journal":{"name":"Journal of biological response modifiers","volume":"9 4","pages":"426-30"},"PeriodicalIF":0.0,"publicationDate":"1990-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13543572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of combinations of interferons and cytotoxic drugs in murine tumor models in vivo.","authors":"S D Harrison,&nbsp;J J Stevens,&nbsp;W R Waud,&nbsp;D J Dykes,&nbsp;S M Schmid,&nbsp;D P Griswold","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>This investigation was conducted to provide preclinical in vivo tumor response data collected under standardized conditions with a range of clinically useful drugs combined with type I (alpha/beta) or type II (gamma) interferon. Murine tumor models used were P388 leukemia, Meth A sarcoma, and B16 melanoma. Eleven cytotoxic drugs were studied. Interferon combinations with cytosine arabinoside provided consistent indications of activity greater than that of the respective single agents. Doxorubicin and cisplatin each prolonged the time to treatment failure, relative to single-agent results, when they were combined with gamma-interferon in the Meth A and B16 models. Interferon combinations with methotrexate, 6-mercaptopurine, 6-thioguanine, ampligen, suramin, 5-fluorouracil, cyclophosphamide, and vinblastine yielded no evidence of any positive therapeutic interactions under the conditions of this study.</p>","PeriodicalId":15063,"journal":{"name":"Journal of biological response modifiers","volume":"9 4","pages":"395-400"},"PeriodicalIF":0.0,"publicationDate":"1990-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13273654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antimelanoma monoclonal antibody-ricin A chain immunoconjugate (XMMME-001-RTA) plus cyclophosphamide in the treatment of metastatic malignant melanoma: results of a phase II trial.","authors":"R Oratz,&nbsp;J L Speyer,&nbsp;J C Wernz,&nbsp;H Hochster,&nbsp;M Meyers,&nbsp;R Mischak,&nbsp;L E Spitler","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Prior studies with the XMMME-001-RTA immunoconjugate composed of an antimelanoma monoclonal antibody and ricin A chain demonstrated some antitumor activity. However, almost all patients studied developed human antimurine antibodies and antiricin antibodies. In an effort to abrogate these host anti-immunotoxin immune responses and thus enhance antitumor activity, we treated 20 patients with the immunoconjugate plus a single dose of intravenous cyclophosphamide. An overall response rate of 20% was observed-predominantly in pulmonary and soft tissue nodules. There was no diminution in antibody responses against either the murine antibody or the ricin moiety. Further studies to elucidate the role of cyclophosphamide in monoclonal antibody therapy are planned.</p>","PeriodicalId":15063,"journal":{"name":"Journal of biological response modifiers","volume":"9 4","pages":"345-54"},"PeriodicalIF":0.0,"publicationDate":"1990-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13541538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Toxicity of intravesical recombinant human tumor necrosis factor in cynomolgus monkeys.","authors":"R R Bahnson,&nbsp;B T Ballou,&nbsp;M S Ernstoff,&nbsp;D V Cramer,&nbsp;F N Schwentker,&nbsp;J M Reiland,&nbsp;T R Hakala","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Six groups of two cynomolgus monkeys were treated with escalating intravesicular doses of recombinant human tumor necrosis factor (rHuTNF) for a 6 week interval. The doses of rHuTNF ranged from 10 ng to 1 mg and were instilled weekly. Two monkeys had instillation of saline only and served as controls. The monkeys were weighed and temperatures determined before, immediately after, and 2 days following each treatment. Cystoscopic examination was performed 2 days after each treatment and blood samples were obtained. At the conclusion of the study, animals were killed and necropsy was performed. There was no observable toxicity from treatment with rHuTNF. There was no difference between treated and control monkeys with respect to temperature, weight, or blood measurements. No drug-induced alteration in bladder morphology was found by either cystoscopic or microscopic pathologic examination.</p>","PeriodicalId":15063,"journal":{"name":"Journal of biological response modifiers","volume":"9 4","pages":"445-7"},"PeriodicalIF":0.0,"publicationDate":"1990-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13543575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Heterogeneity in lectin-binding characteristics of human lymphokine-activated killer cells.","authors":"T Maruyama,&nbsp;Y Imai,&nbsp;K Harada,&nbsp;T Okada,&nbsp;M Takano,&nbsp;Y Ikeda,&nbsp;G Toda,&nbsp;H Oka,&nbsp;T Osawa","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The binding of various lectins to human lymphokine-activated killer (LAK) cells was investigated. Human peripheral blood lymphocytes were cultured for 3 days with recombinant interleukin-2 (rIL-2), and then stained with 20 kinds of lectins. There were four types of lectin-binding patterns: (a) negative staining; (b) weakly positive staining; (c) strongly positive staining; and (d) two populations, one weakly and one strongly positive staining. Among the 20 kinds of lectins, both Lens culinaris agglutinin (LCA) and Pisum sativum agglutinin (PSA) showed two peaks in the staining patterns on LAK cells (type 4). We separated these two populations of LAK cells by using a cell sorter, and assayed them for cytotoxic activity against 51Cr-labeled Hela cells. The LAK cells that were strongly stained by LCA or PSA [LCA (or PSA)-bright LAK cells] showed stronger cytotoxic activity than the LAK cells that were weakly stained by LCA or PSA [LCA (or PSA)-dull LAK cells]. Furthermore, we separated lymphocytes with LCA or PSA before culturing them with rIL-2 (LAK precursor), and we found that both LCA-bright and PSA-bright lymphocytes can develop into LAK cells with higher cytolytic activity. LCA-bright lymphocytes kept their ability to be stained strongly with LCA even after culture with rIL-2 for 3 days. Similarly, LCA-dull lymphocytes were still stained weakly after culture with rIL-2. Two-color assay of LAK cells revealed that 78% of NK (CD16+)-LAK cells and 46% of T (CD3+)-LAK cells were LCA-bright cells.(ABSTRACT TRUNCATED AT 250 WORDS)</p>","PeriodicalId":15063,"journal":{"name":"Journal of biological response modifiers","volume":"9 4","pages":"378-86"},"PeriodicalIF":0.0,"publicationDate":"1990-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13543569","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Implications of leukoregulin to autologous tumor-specific human T-cell populations.","authors":"C L Slingluff,&nbsp;H F Seigler,&nbsp;T L Darrow,&nbsp;C H Evans","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Interactions between the cellular and humoral compartments of the human immune system are well documented. Leukoregulin (LR) is a hormone with the ability to upregulate the natural killer (NK) phenomenon by increasing target cell sensitivity to NK lymphocyte cytotoxicity. In the present report, the interactions between LR and human cytotoxic T-lymphocytes (CTLs) are described. Two cultured T-cell populations are specifically cytotoxic for autologous human melanoma and fail to lyse allogeneic melanoma, K562, or autologous peripheral blood lymphocytes (PBLs) in 4 h chromium release assays. Pretreating allogeneic melanoma or K562 with LR resulted in 19-67% lysis at an effector:target (E:T) ratio of 5:1, while no more than 10% lysis was observed without LR. Autologous PBLs were also subject to lysis when pretreated with LR (50% at an E:T of 40:1 with LR, and 2% without LR). The observed effect was dose-related and was most effectively inhibited by autologous cold targets, but persisted in the presence of antibody to human lymphocyte antigen class I antigens (w6/32). Lysis of autologous melanoma was not increased by pretreatment with LR. LR appears to mediate lysis of melanoma, NK targets, and normal PBLs by tumor specific CTLs. The effect is dose-related and non-major histocompatibility complex-restricted. The data do not support a significant role for LR in the normal physiology of human CTLs, but the striking effects in vitro may prove to be experimentally or therapeutically useful.</p>","PeriodicalId":15063,"journal":{"name":"Journal of biological response modifiers","volume":"9 4","pages":"387-94"},"PeriodicalIF":0.0,"publicationDate":"1990-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13543570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recombinant interferon-alpha 2a and vinblastine in advanced renal cell cancer: a clinical phase I-II study.","authors":"P Kellokumpu-Lehtinen,&nbsp;E Nordman","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Twenty patients with metastatic renal cell cancer were treated with a combination of recombinant interferon-alpha 2a (Roferon-A), 18 MU intramuscularly three times weekly and vinblastine 0.1 mg/kg intravenously once every 3 weeks. Three patients experienced a complete response (CR) (15%) and three a partial response (PR) (15%). The response duration was 3, 13, and 15 months in the CR group, and PRs lasted 11, 13, and 14 months. Constitutional symptoms like fever, anorexia, and fatigue were the most common side effects. One patient had reversible hepatitis, which was probably unrelated to antineoplastic therapy. Dose modifications had to be made in seven patients due to leukopenia or thrombocytopenia. No very serious side effects were noticed. In view of what has been reported previously, the overall response rate (30%) of this regimen is good and tolerance of the treatment is acceptable.</p>","PeriodicalId":15063,"journal":{"name":"Journal of biological response modifiers","volume":"9 4","pages":"439-44"},"PeriodicalIF":0.0,"publicationDate":"1990-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13543574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}