{"title":"MHC-unrestricted immune surveillance of leukemia.","authors":"G Pawelec","doi":"10.1089/cbr.1994.9.265","DOIUrl":"https://doi.org/10.1089/cbr.1994.9.265","url":null,"abstract":"<p><p>The characteristics of natural killer (NK) cells and their role in immunosurveillance of cancer is reviewed. Evidence derived from in vitro and in vivo experiments is in favor of an important role of NK cells in host resistance to leukemia, as illustrated by studies of untreated patients, patients treated with biological response modifiers and by bone marrow transplantation.</p>","PeriodicalId":79322,"journal":{"name":"Cancer biotherapy","volume":"9 3","pages":"265-88"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cbr.1994.9.265","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18820608","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 commentary on the first international conference on engineered vaccines for cancer and AIDS; the \"coming of age\" of tumor immunology.","authors":"G Ada","doi":"10.1089/cbr.1994.9.71","DOIUrl":"https://doi.org/10.1089/cbr.1994.9.71","url":null,"abstract":"","PeriodicalId":79322,"journal":{"name":"Cancer biotherapy","volume":"9 1","pages":"71-4"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cbr.1994.9.71","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18535967","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}
M E Marshall, C M Tangen, J L Berenberg, S P Balcerzak, T Brown, J S Macdonald
{"title":"Treatment of advanced colorectal carcinoma with 5-fluorouracil, leucovorin and Roferon-A: a Southwest Oncology Study Group Study.","authors":"M E Marshall, C M Tangen, J L Berenberg, S P Balcerzak, T Brown, J S Macdonald","doi":"10.1089/cbr.1994.9.301","DOIUrl":"https://doi.org/10.1089/cbr.1994.9.301","url":null,"abstract":"<p><p>Based upon prior data suggesting that alpha-interferon possesses chemomodulatory activity, a pilot study was conducted in which patients with advanced colorectal carcinoma were treated with 5-fluorouracil (5-FU), leucovorin (LV) and Roferon-A. Treatment consisted of LV 20 mg/m2 i.v. push followed by 5-FU, 425 mg/m2 i.v. push daily for 5 days every 4 weeks for 2 cycles, then every 5 weeks; Roferon-A 9 million units subcutaneously was given three times weekly every week. Forty-six eligible patients with bidimensionally measurable disease who had received no prior chemotherapy for advanced disease were treated with this regimen. The most frequent toxicity was leukopenia with 80% of patients experiencing some degree of leukopenia and the most severe toxicity was granulocytopenia with 46% of patients experiencing granulocyte counts < 1,000/mm3. Among the 46 eligible patients, the objective response rate was 13% (95% confidence interval, 5-26%). Thirty-five of the 46 patients have died with a median survival of 17 months. This regimen has significant toxicity and insufficient activity against advanced colorectal carcinoma to warrant further trials.</p>","PeriodicalId":79322,"journal":{"name":"Cancer biotherapy","volume":"9 4","pages":"301-6"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cbr.1994.9.301","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18723683","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}
M Meffert, E L Hanninen, T Menzel, A Schomburg, S Duensing, I Dallmann, J Grosse, S Vocke, J Buer, M Deckert
{"title":"In vivo time and dose dependency of interleukin-6 secretion in response to low-dose subcutaneous recombinant interleukin-2.","authors":"M Meffert, E L Hanninen, T Menzel, A Schomburg, S Duensing, I Dallmann, J Grosse, S Vocke, J Buer, M Deckert","doi":"10.1089/cbr.1994.9.307","DOIUrl":"https://doi.org/10.1089/cbr.1994.9.307","url":null,"abstract":"<p><p>Serum concentrations of Interleukin-6 (IL-6) were determined in renal cell carcinoma patients treated with low-dose subcutaneous human recombinant interleukin-2 (rIL-2). In all patients, administration of rIL-2 resulted in a significant increase in IL-6 serum levels to peak values within 4 to 6 hours as measured by enzyme-linked immunosorbent assays (ELISA). Repetitive administration of rIL-2 induced significantly lower IL-6 serum peaks when compared to the initial administration of rIL-2. Cumulative IL-6 release, as expressed by the area under the concentration curve (AUC), appeared to be independent of rIL-2 dose distribution (10 million IU rIL-2/m2 versus 20 million IU rIL-2/m2), and IL-6 serum peaks showed no direct dose dependency. Prior rIL-2 immunotherapy had no measurable effect on rIL-2 induced IL-6 release, while steroids resulted in a significant suppression of secondary IL-6 did not correlate with response to rIL-2 therapy or survival of rIL-2 treated renal cell carcinoma patients.</p>","PeriodicalId":79322,"journal":{"name":"Cancer biotherapy","volume":"9 4","pages":"307-16"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cbr.1994.9.307","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18723684","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":"Improved delivery through biological membranes. LXI: Design, synthesis, and evaluation of a lipolol-based intradermal drug targeting system for 5-fluorouracil.","authors":"P J Chikhale, E Marvanyos, N S Bodor","doi":"10.1089/cbr.1994.9.245","DOIUrl":"https://doi.org/10.1089/cbr.1994.9.245","url":null,"abstract":"<p><p>This report describes initial studies with the lipolyl ester of 1-carboxypropylcarbamoyl-FU (LE-CPCFU) which was designed to enhance the dermal delivery of the antitumor agent 5-fluorouracil (FU). The design of LE-CPCFU was based upon our previous observation that sulfur-based chemical drug targeting systems were localized within the skin and improved the delivery of the parent drug to the dermal tissue (Chikhale et al., 1993; Bodor et al., 1982; Bodor and Sloan, 1982). In the in vitro test system that used freshly-excised guinea-pig skin, LE-CPCFU was found to enhance FU delivery to the skin 2- to 5-fold compared to underivatized FU. Neither LE-CPCFU nor its acid metabolite 1-carboxypropylcarbamoyl-FU (CPCFU) could be detected in the skin or receiver during the diffusion experiments even though LE-CPCFU and CPCFU were found to be reasonably stable in aqueous pH 7.4 buffer and during the analytical procedure. FU which was released from LE-CPCFU in the skin subsequently diffused into the receiver. Thus, LE-CPCFU was observed to improve FU delivery to the skin during the initial time period of the study (0-4 hr). This study indicates that LE-CPCFU in the guinea-pig skin was hydrolyzed to form FU in the skin serving as an intradermal drug delivery system for the antitumor agent. Thus, LE-CPCFU could prove to reduce the systemic toxicity of FU by enhancing the local skin concentration and minimizing the systemic concentration of the antitumor agent as compared to underivatized FU.</p>","PeriodicalId":79322,"journal":{"name":"Cancer biotherapy","volume":"9 3","pages":"245-52"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cbr.1994.9.245","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18820607","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":"Increased oxygen tensions influence subset composition of the cellular immune system in aged mice.","authors":"A K Lee, R B Hester, J H Coggin, S F Gottlieb","doi":"10.1089/cbr.1994.9.39","DOIUrl":"https://doi.org/10.1089/cbr.1994.9.39","url":null,"abstract":"<p><p>In acute and chronic experiments, each of eight groups of aged mice were assigned separately to different pressures of oxygen to which it was to be exposed. Lymphocytes from spleen, thymus, and peripheral blood were analyzed following oxygen exposure. Subset populations changed depending on the oxygen tension. Variable changes were observed in total numbers of lymphocytes, lymphocyte subsets, B cells, and macrophages depending on the organ studied and the oxygen pressure to which the mice were exposed. There were differences between acute and chronic exposure suggestive of adaptation to environmental stressors. The suggestion is made that the immune system has a reserve capacity that can be influenced by oxygen and, thereby, theoretically capable of being pharmacologically manipulated to assist patients with altered immune systems to promote defense mechanisms or, under certain circumstances, reduce autoimmunity. It is hypothesized that an underlying hypoxia may be involved in the age-associated decline in the immune system.</p>","PeriodicalId":79322,"journal":{"name":"Cancer biotherapy","volume":"9 1","pages":"39-54"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cbr.1994.9.39","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18811598","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":"Generation of specific antitumor cytotoxic T-lymphocytes in monoculture can be inhibited by T-suppressors from tumor-bearing mice.","authors":"Lupatov AYu, B D Brondz","doi":"10.1089/cbr.1994.9.123","DOIUrl":"https://doi.org/10.1089/cbr.1994.9.123","url":null,"abstract":"<p><p>A new model for the generation of specific antitumor cytotoxic T lymphocytes (CTL) was proposed. In contrast to other models, it allows to generate secondary effector CTL (CTL-2) without tumor stimulator cells in vitro (in monoculture). C57BL/10 mice or/and C57BL/6 mice were immunized by injection with gamma-irradiated syngeneic tumor cells into the footpads. For estimation of cytotoxic activity, chromium-51 release assay was used. It has been shown that effector CTL were absent in the lymph nodes after 1-fold as well as 2-fold immunization. Cytotoxic cells have not been found in 1-fold immunization even after maturation of the lymphocytes in monoculture. Specific CTL were detected only after secondary immunization and subsequent cultivation in vitro. Effector cells had Thy1.2, CD8+, CD4- phenotype. Presence in vitro of exogenous recombinant interleukin 2 (rIL-2) was needed for the generation of CTL-2 against Mech-11 sarcoma but not against EL4 lymphoma. The spleen cells from B10 mice with progressively growing Mech-11 tumor specifically suppressed the maturation of CTL-2 against Mech-11 in monoculture. Since suppression took place in the presence of exogenous rIL2 in monoculture, it was suggested that suppression was not resulted by negative influence of the suppressor cells upon endogenic IL-2 production. The treatment of the suppressor cells with monoclonal antibody (Mab) against Thy1.2 as well as against CD4 or CD8 markers plus complement (C') considerably decreased Ts activity. Obviously, two distinct subsets of T-lymphocytes were required for suppression.</p>","PeriodicalId":79322,"journal":{"name":"Cancer biotherapy","volume":"9 2","pages":"123-9"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cbr.1994.9.123","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18812766","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 liposome-muramyl tripeptide combined with recombinant canine granulocyte colony-stimulating factor on canine monocyte activity.","authors":"I D Kurzman, H Cheng, E G MacEwen","doi":"10.1089/cbr.1994.9.113","DOIUrl":"https://doi.org/10.1089/cbr.1994.9.113","url":null,"abstract":"<p><p>Liposome-muramyl tripeptide-phosphatidylethanolamine (L-MTP-PE) has been shown to activate monocytes in vivo to become tumoricidal resulting in reduction in metastasis as well as prolongation of survival time in murine and canine tumor models. Granulocyte colony-stimulating factor (G-CSF) is a cytokine which will stimulate the proliferation of granulocytes as well as monocytes. Recombinant canine G-CSF (rcG-CSF) was administered to normal dogs as a method of increasing the monocyte population prior to in vivo monocyte activation using L-MTP-PE. rcG-CSF administration resulted in a 3.5-fold increase in absolute monocyte counts and when combined with L-MTP-PE, resulted in an enhanced level of serum tumor necrosis factor-alpha activity compared to dogs treated with L-MTP-PE alone. G-CSF alone did not affect monocyte cytostatic activity, however, dogs receiving G-CSF had a significant increase in monocyte cytostatic activity following L-MTP-PE. The combined use of CSFs and effector cell activators deserves further evaluation in clinical trials.</p>","PeriodicalId":79322,"journal":{"name":"Cancer biotherapy","volume":"9 2","pages":"113-21"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cbr.1994.9.113","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18535968","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}
U Zorn, I Dallmann, J Grosse, H Kirchner, H Poliwoda, J Atzpodien
{"title":"Induction of cytokines and cytotoxicity against tumor cells by Newcastle disease virus.","authors":"U Zorn, I Dallmann, J Grosse, H Kirchner, H Poliwoda, J Atzpodien","doi":"10.1089/cbr.1994.9.225","DOIUrl":"https://doi.org/10.1089/cbr.1994.9.225","url":null,"abstract":"<p><p>The use of NDV as biological adjuvant in vaccines against human cancer is still actual in several clinical treatment protocols. In this study, we have investigated in vitro-effects of Newcastle disease virus (NDV) strain 73-T on isolated mononuclear blood cells and cultured tumor cells. Cellular cytotoxicity of PBMC freshly isolated from healthy donors against tumor cells was enhanced significantly (p < 0.01) after coincubation of NDV with effector cells. NDV failed to enhance cytotoxicity of effector cells when PBMC were stimulated three days with 500 IU recombinant interleukin-2 (rIL-2) per ml prior to coincubation with the virus. No significant enhancement of cellular lysis was seen when only target cells were coincubated with NDV. As shown by depletion of various lymphocyte subsets, NK cells were the predominant mediator of lysis. Enhancement of cytotoxicity correlated with the induction of interferon-alpha (IFN-alpha) in PBMC by NDV. NDV also induced high amounts of tumor necrosis factor-alpha (TNF-alpha) in PBMC. Induction of interferon-gamma (IFN-gamma) was weak. A direct cytopathic effect (CPE) of NDV on different target cells was detected by colorimetric measurement of metabolic cell activity. The human tumor cell lines A-498, A-704, Caki-1, Caki-2, and K-562 and the fibroblast line MRC-5 showed progressive cellular destruction 48 h after infection with NDV, whereas PBMC and Daudi cells remained unaffected during the observation period. The nontransformed monkey kidney cell line CV-1 and the transformed monkey kidney cell line COS-1 were both lysed by NDV with marginal difference in time course of CPE. Our results indicate a reasonable potential of pleiotropic modifications of the immune response against tumors by NDV.</p>","PeriodicalId":79322,"journal":{"name":"Cancer biotherapy","volume":"9 3","pages":"225-35"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cbr.1994.9.225","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18820605","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 vitro effects of pentoxifylline and doxorubicin on cell survival and DNA damage in sensitive and MDR-P388 leukemia cells.","authors":"A Viladkar, M Chitnis","doi":"10.1089/cbr.1994.9.143","DOIUrl":"https://doi.org/10.1089/cbr.1994.9.143","url":null,"abstract":"<p><p>The utility of chemosensitizers to improve efficacy of chemotherapy is now gaining importance. This report investigated whether an active hemorheological agent, pentoxifylline (PTX), can circumvent drug resistance in parental (P388/S) and multidrug resistant (P388/DOX) P388 leukemia cells. For detection of doxorubicin (DOX) resistance and reversal of this resistance by PTX, the incorporation of nucleic acid precursor was measured after addition of DOX and PTX, respectively. The effect of PTX on the induction of DNA strand breaks by DOX was also examined. Increased fragmentation of DNA was illustrated in P388/DOX leukemia cells exposed to the combination of DOX and PTX. The most prominent feature of the multidrug-resistant cell is the reduced accumulation of the drug intracellularly. P388/DOX cells showed less accumulation of DOX in the cell as compared to that of the parental cell line. Further studies demonstrated that PTX significantly enhanced the intracellular accumulation of DOX in both the cell lines. These studies warrant the use of PTX as an adjuvant in cancer chemotherapy.</p>","PeriodicalId":79322,"journal":{"name":"Cancer biotherapy","volume":"9 2","pages":"143-51"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cbr.1994.9.143","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18812768","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}