Journal of biological response modifiers最新文献

{"title":"Dissociation of thymidine incorporation and transferrin receptor expression from cell growth and c-myc accumulation in alpha-interferon-treated cells.","authors":"L M Meadows,&nbsp;D J George,&nbsp;R E Kaufman","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Alpha-interferon is capable of altering the pattern of growth of both normal and neoplastic cells, but the pathways essential to sensitivity and resistance to alpha-interferon are unknown. To explore the growth inhibition induced by alpha-interferon, we examined the interferon-sensitive cell line Daudi and the resistant cell line HL-60. In Daudi, alpha-interferon induced a fall in c-myc mRNA accumulation at 24 h, inhibited tritiated thymidine ([3H]Thd) uptake at 48-72 h, and inhibited proliferation at 72-96 h. The half-life of c-myc mRNA was shortened from 31 to 13 min by alpha-interferon treatment. In HL-60, no alteration in c-myc accumulation or cell growth was observed, but [3H]Thd uptake was inhibited by 49%. Exogenous thymidine partially reversed the effects of alpha-interferon on [3H]Thd incorporation. The number of transferrin receptors, as measured by immunofluorescence, was unaffected by alpha-interferon in both cell lines. We conclude that the growth inhibitory effects of alpha-interferon are neither dependent upon inhibition of thymidine metabolism nor on expression of the transferrin receptor, but may be linked to control of c-myc.</p>","PeriodicalId":15063,"journal":{"name":"Journal of biological response modifiers","volume":"9 2","pages":"212-20"},"PeriodicalIF":0.0,"publicationDate":"1990-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13340485","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":"An improved method for growing murine tumor-infiltrating lymphocytes with in vivo antitumor activity.","authors":"J C Yang,&nbsp;D Perry-Lalley,&nbsp;S A Rosenberg","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Tumor-infiltrating lymphocytes (TILs) are host T cells that can be grown from fresh murine and human tumors using interleukin-2 (IL-2) in bulk cultures. These activated T cells have been shown to have significant antitumor activity both in vitro and in vivo. A technique is described for the separation of Thy-1.2-positive TILs from fresh murine tumors using antibody-coated magnetic beads, permitting the examination of growth conditions for these cells. TILs with increased therapeutic efficacy are obtained from the immunogenic MCA 38 and MCA 105 tumors when culture conditions employing low levels of IL-2 (10 vs. 1,000 U/ml) and irradiated autologous tumor restimulation are used. TILs grown under these conditions can mediate a 93% reduction of 3-day-old established pulmonary metastases when as few as 2.5 x 10(5) cells are adoptively transferred with systemic IL-2. These culture conditions are utilized to grow TILs from the nonimmunogenic MCA 102 tumor for which bulk TIL culture methods are unsuccessful. MCA 102 TILs grown in this fashion demonstrate in vivo therapeutic efficacy against established autologous pulmonary metastases.</p>","PeriodicalId":15063,"journal":{"name":"Journal of biological response modifiers","volume":"9 2","pages":"149-59"},"PeriodicalIF":0.0,"publicationDate":"1990-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13129426","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":"Interleukin-6 induction by a muramyltripeptide derivative in cancer patients.","authors":"H Frost,&nbsp;J L Murray,&nbsp;H A Chaudri,&nbsp;J Van Damme","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Interleukin-6 (IL-6) was measured in sera from 26 patients with advanced malignancies before and after an I.V. infusion of muramyltripeptide-phosphatidylethanolamine (MPT-PE) in liposomes. Significantly elevated IL-6 could be measured 2 and 4 h after medium (0.25-0.5 mg/m2) and high (1.0-6.0 mg/m2) doses of the drug accompanied by a rise in body temperature. The biological activity of IL-6 in sera could be inhibited in vitro by monoclonal antibodies against IL-6. Other biological effects of MTP-PE in vivo such as leukocytosis and elevated acute phase reactants are discussed in view of increased IL-6 levels. It is concluded that MTP-PE in liposomes generates increased amounts of IL-6 measurable in serum several hours after administration. IL-6 could therefore play an important role in the biological response modification induced by the drug.</p>","PeriodicalId":15063,"journal":{"name":"Journal of biological response modifiers","volume":"9 2","pages":"160-6"},"PeriodicalIF":0.0,"publicationDate":"1990-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13490801","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":"In vivo effects of cytokines on development of natural killer cells and antitumor activity in lethally irradiated bone marrow transplanted recipients.","authors":"C Riccardi,&nbsp;G Migliorati,&nbsp;L Cannarile,&nbsp;F D'Adamio,&nbsp;L Frati,&nbsp;R B Herberman","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>We have evaluated the effects of combinations of various cytokines on the reconstitution of natural killer (NK) cell activity and resistance to metastases from B16 melanoma, in lethally irradiated mice transplanted with syngeneic bone marrow. Treatment with some combinations of interleukin-2 (IL-2) and other cytokines (IL-2 + IL-1 + TNF alpha or IL-2 + IL-1 + LT) induced appreciably greater and more rapid augmentation of NK cell regeneration than IL-2 alone, as measured in vitro in the 4-h 51Cr release assay against YAC-1 or in vivo in an assay of lung clearance of 125IUdR-labeled tumor cells. The same treatments also induced significant augmentation of in vivo resistance against pulmonary metastases in C57BL/6 mice injected with B16 melanoma cells. These data indicate that stimulation of NK activity in tumor-bearing bone marrow transplanted recipients may be of value in the control of metastatic disease.</p>","PeriodicalId":15063,"journal":{"name":"Journal of biological response modifiers","volume":"9 1","pages":"15-23"},"PeriodicalIF":0.0,"publicationDate":"1990-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13333650","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":"Therapeutic efficacy of recombinant tumor necrosis factor alpha in an experimental model of human prostatic carcinoma.","authors":"E R Sherwood,&nbsp;T R Pitt Ford,&nbsp;C Lee,&nbsp;J M Kozlowski","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Prostatic carcinoma represents the second leading cause of cancer mortality in men and is responsible for over 25,000 deaths each year. Currently, no curative therapy is available for metastatic carcinoma of the prostate. The present studies were undertaken to assess the efficacy of recombinant tumor necrosis factor alpha (TNF) in the therapy of experimental prostatic carcinoma. TNF was cytotoxic to the prostate cancer cell lines PC3, DU145, and LNCAP but not benign prostatic epithelial and stromal cells in vitro. The sensitivity of the prostatic carcinoma lines to TNF-mediated cytotoxicity was enhanced by the presence of actinomycin D. Intravenous administration of TNF (50-100 micrograms/kg) to nude mice bearing subcutaneous PC3 tumors resulted in significant inhibition of primary tumor growth compared to control. TNF was also effective in reducing the growth of intraabdominal PC3 tumors induced by intrasplenic injection of PC3. Furthermore, the incidence of microscopic PC3 foci in the spleen, liver, lung, and diaphragm was diminished in mice receiving TNF therapy. These studies demonstrate the potential of TNF in the therapy of human prostatic carcinoma.</p>","PeriodicalId":15063,"journal":{"name":"Journal of biological response modifiers","volume":"9 1","pages":"44-52"},"PeriodicalIF":0.0,"publicationDate":"1990-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13469353","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":"Antiviral activity of the novel immune modulator 7-thia-8-oxoguanosine.","authors":"D F Smee,&nbsp;H A Alaghamandan,&nbsp;H B Cottam,&nbsp;W B Jolley,&nbsp;R K Robins","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>A novel thiazolopyrimidine nucleoside, 5-amino-3-beta-D-ribofuranosylthiazolo[4,5-d]pyrimidine-2,7(3H,6H) -dione (7-thia-8-oxoguanosine), was evaluated for antiviral activity in rodent models, and at 50-200 mg/kg prevented death in mice inoculated intraperitoneally (i.p.) with Semliki Forest, San Angelo, and banzi viruses when administered i.p. before virus challenge. Similarly, the nucleoside was effective against an intranasal challenge of rat coronavirus in suckling rats, with activity present when treatment started as late as 4 h after virus inoculation. Protection was observed against herpes type 1 and murine cytomegalovirus (both inoculated i.p.) infections, and encephalitis induced by intracerebral inoculation of a human coronavirus in mice. Friend leukemia virus splenomegaly was more severe in drug-treated animals than in placebos. This immune modulator is promising for the treatment of animal and human diseases.</p>","PeriodicalId":15063,"journal":{"name":"Journal of biological response modifiers","volume":"9 1","pages":"24-32"},"PeriodicalIF":0.0,"publicationDate":"1990-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13310454","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":"Synergistic actions of picibanil (OK-432) on recombinant interleukin-2 induction of tumor-infiltrating lymphocyte expansion, cytotoxicity, and phenotypic differentiation.","authors":"R Lafreniere,&nbsp;K Borkenhagen,&nbsp;L D Bryant,&nbsp;E Ng,&nbsp;S Hayton","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Tumor-infiltrating lymphocytes (TILs) comprise a subpopulation of lymphoid cells that infiltrate into growing tumors. These cells can be activated in vitro with recombinant interleukin-2 (rIL-2) to become highly cytotoxic against fresh tumor targets in vitro and against a variety of systemic metastases in vivo. OK-432 is a well-known inducer of NK cells and immune effector T cells. This study was designed to evaluate the effects of OK-432 on (a) the generation and (b) the cytotoxic potential of rIL-2-induced TILs. When TILs obtained from a murine colon adenocarcinoma (the MC-38 tumor) were cultured in complete media supplemented with 100 U of rIL-2/ml and 1.0 microgram of OK-432/ml, the number of TILs generated was greater than that seen with rIL-2 or OK-432 alone (number of TILs on day 15 of culture: 100 U of rIL-2/ml: 268 x 10(5) TILs; 1.0 microgram of OK-432/ml: 30 x 10(5) TILs; 100 U of rIL-2/ml + 1.0 microgram of OK-432/ml: 528 x 10(5) TILs). Higher concentrations of OK-432 had deleterious effects on TIL growth characteristics. TILs generated in 100 U of rIL-2 and 1.0 microgram of OK-432/ml of complete media demonstrated greater tumor lysis compared to rIL-2 alone (% lysis against MCA-102 target; 100 U of rIL-2/ml: 12%; 100 U of rIL-2/ml and 1.0 microgram of OK-432/ml: 50%; effector target ratio 20:1; p less than 0.001). Similar results were seen against the NK-sensitive YAC-1 lymphoma target.(ABSTRACT TRUNCATED AT 250 WORDS)</p>","PeriodicalId":15063,"journal":{"name":"Journal of biological response modifiers","volume":"9 1","pages":"53-60"},"PeriodicalIF":0.0,"publicationDate":"1990-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13333607","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":"A pilot study of intralymphatic interleukin-2. I. Cytotoxic and surface marker changes of peripheral blood lymphocytes.","authors":"H Shau,&nbsp;V Isacescu,&nbsp;Y Ibayashi,&nbsp;Y Tokuda,&nbsp;S H Golub,&nbsp;J L Fahey,&nbsp;G P Sarna","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Patients with metastatic solid tumors were treated with six escalating doses of weekly intralymphatically injected recombinant interleukin 2 (i.l. IL-2). Nine patients completed the treatment and were evaluated for immunologic features of their peripheral blood lymphocytes (PBLs). The patients' PBL counts increased 4 days after the first i.l. IL-2 injection. The cell counts remained higher than baseline in week 6 prior to the last i.l. IL-2 injection. However, the PBL number decreased below baseline 1 day after the sixth injection, and recovered to normal levels after 3 days more. Natural killer (NK) activity showed similar changes when calculated as total activity per ml of blood. In vitro 1 h treatment of PBLs with IL-2 greatly enhanced NK cytotoxicity. The enhancement was only slight in the first week of i.l. IL-2 treatment, but was significantly greater on day 35 (7 days after dose 5) and day 39 (4 days after dose 6). In contrast, the increase was similar to the baseline on day 36, the day after the sixth injection. No lymphokine-activated killer activity was detected in the patients' PBLs with or without short-term in vitro IL-2 treatment. Besides the NK cytotoxic function, lymphoid subpopulations were evaluated numerically for total T cells (CD3/OKT3), T-cell subsets (CD4/OKT4 and CD8/OKT8), B cells (OKB7), NK cells (CD56/NKH1/Leu19, CD16/Leu11), and monocytes/NK cells (CD11b/OKM1). The activation markers (HLA-DR, CD25/Tac, and CD38/OKT10/Leu17) were also included. Intralymphatic IL-2 treatment had no effect on the PBL surface marker expression in the first week of treatment. However, by week 6, the percentages of cell populations expressing the NK-associated antigens CD56, CD16, and CD11b were significantly increased. In contrast, the percentage of CD3-positive T cells showed no change or a marginal decrease. Prior to and after i.l. IL-2 treatment, the CD56-positive cells in the PBLs were predominantly CD16 positive and CD3 negative. The i.l. IL-2 treatment did not induce PBL proliferation, or changes in the expression of CD25 (Tac), HLA-DR, CD38, CD4, CD8, CD57, or OKB7 in the patients' PBL. These results indicate that i.l. IL-2 treatment does affect the total number of PBLs, the cells expressing NK activity, and NK-associated surface markers.</p>","PeriodicalId":15063,"journal":{"name":"Journal of biological response modifiers","volume":"9 1","pages":"71-80"},"PeriodicalIF":0.0,"publicationDate":"1990-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13469354","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 of cell surface structures involved in cytotoxicity mediated by lymphokine activated killer cells.","authors":"P Bean,&nbsp;R Agah,&nbsp;A Mazumder","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Lymphokine activated killer (LAK) cells mediate the lysis of a variety of histologically distinct tumor targets. We investigated the nature and diversity of the structures involved in the recognition phenomenon by evaluating the effects of treating effector and target cells with trypsin and chymotrypsin, enzymes that disrupt surface protein molecules. Chymotrypsin and trypsin treatment of B16 target cells, a murine melanoma cell line, significantly abolished killing by LAK cells. Alternatively, neither of these treatments in P815 cells, a murine mastocytoma cell line, affected killing by LAK cells. Moreover, we found a differential effect of both these enzymes on YAC-1 cells, a murine leukemia cell line, with trypsin having a less inhibitory effect on cytolysis than chymotrypsin. The nature of the LAK cell receptor that presumably plays a role in binding target antigen was also investigated. Treatment of LAK cells with chymotrypsin significantly reduced lysis of the B16 and YAC-1 target cell types. However, trypsin treatment of the effectors only inhibited killing of the B16 tumor cell line. Cytotoxicity exerted against YAC-1 remained unaltered upon trypsinization of LAK cells. These cumulative results indicate heterogeneity of both the receptors on the LAK cells and the surface antigen molecules recognized on these targets. The use of YAC-1 as a target provided us with a tool to compare the LAK with the natural killer (NK) systems. The overall effect of proteolytic enzyme treatment in reducing cell lysis was more pronounced in the NK than in the LAK system.(ABSTRACT TRUNCATED AT 250 WORDS)</p>","PeriodicalId":15063,"journal":{"name":"Journal of biological response modifiers","volume":"9 1","pages":"92-7"},"PeriodicalIF":0.0,"publicationDate":"1990-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13333608","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":"Depressed in vitro T cell responses concomitant with augmented interleukin-2 responses by lymphocytes from cancer patients following in vivo treatment with interleukin-2.","authors":"J A Hank,&nbsp;J A Sosman,&nbsp;P C Kohler,&nbsp;R Bechhofer,&nbsp;B Storer,&nbsp;P M Sondel","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Peripheral blood lymphocytes obtained from cancer patients receiving interleukin-2 (IL-2) on two separate clinical protocols were evaluated for their in vitro responses to IL-2, alloantigens, and PHA. IL-2 in vivo induced enhanced in vitro proliferative responses to IL-2 and diminished in vitro proliferative responses to phytohemagglutinin (PHA) and alloantigens. Alloinduced cytotoxic T cell responses were also depressed following in vivo IL-2. We examined the kinetics of the in vitro proliferative response to PHA and IL-2 and found that while the response of lymphocytes primed in vivo with IL-2 to PHA was depressed at all times during the 2 week in vitro exposure, the response to IL-2 peaked earlier and higher than did the response to IL-2 by lymphocytes obtained prior to IL-2 therapy. These contrasting effects on antigen-induced T cell responses vs. IL-2 induced nonspecific proliferative and cytotoxic responses suggest the importance of dose and timing of IL-2 administration when used to enhance antigen-specific T cell responses or as an immune enhancing agent combined with vaccines.</p>","PeriodicalId":15063,"journal":{"name":"Journal of biological response modifiers","volume":"9 1","pages":"5-14"},"PeriodicalIF":0.0,"publicationDate":"1990-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13333651","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}