{"title":"Cancer research: does it deliver for the patient?","authors":"R K Oldham","doi":"10.1089/cbr.1994.9.99","DOIUrl":"https://doi.org/10.1089/cbr.1994.9.99","url":null,"abstract":"","PeriodicalId":79322,"journal":{"name":"Cancer biotherapy","volume":"9 2","pages":"99-102"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cbr.1994.9.99","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18812771","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":"Proteolytic enzymes and amylase induce cytokine production in human peripheral blood mononuclear cells in vitro.","authors":"L Desser, A Rehberger, W Paukovits","doi":"10.1089/cbr.1994.9.253","DOIUrl":"https://doi.org/10.1089/cbr.1994.9.253","url":null,"abstract":"<p><p>In vitro treatment of human peripheral blood mononuclear cells (PBMNC) with proteolytic enzymes (bromelain, papain) and amylase leads to the production of large amounts of tumor necrosis factor-alpha (TNF-alpha), interleukin-1-beta (IL-1 beta), and interleukin-6 (IL-6) in a time and dose dependent manner. Increased TNF-alpha and IL-6 production was already found after 4-6 hours of incubation, and plateau levels were reached after 12-16 hours. Plateau levels up to 1500 pg TNF-alpha/ml/10(6) PBMNC, 13000 pg IL-1 beta/ml/10(6) PBMNC, and 23000 pg IL-6/ml/10(6) PBMNC were observed. Control cultures contained below 35 pg/ml/10(6) PBMNC of TNF-alpha, IL-1 beta or IL-6. In contrast to TNF-alpha which was undetectable after more than 24 hours, peak levels of IL-1 beta and IL-6 were still present at 24 hours. After incubation of the enzyme solution for some hours at 56 degrees C the cytokine inducing capacity disappeared. Neutralization experiments with inactivating antibodies, radioimmunoassay, and western blotting after electrophoretic separation showed that the TNF-like activity found in the lytic assay was due to TNF-alpha. Interferon-alpha (IFN-alpha) and Interferon-gamma (IFN-gamma), which had no effect alone, synergistically increased TNF-alpha production when applied together with the enzymes. A commercial mixture of these enzymes (Wobenzym), which was also investigated, showed a similar concentration and time dependence, as well as synergism with the interferons. A synergistic effect on TNF-alpha production was also found with the enzymes and phorbol ester (PMA).</p>","PeriodicalId":79322,"journal":{"name":"Cancer biotherapy","volume":"9 3","pages":"253-63"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cbr.1994.9.253","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18536319","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":"Suppressive effects on cancer cell proliferation of the enhancement of superoxide dismutase (SOD) activity associated with the protein-bound polysaccharide of Coriolus versicolor QUEL.","authors":"Y Kobayashi, K Kariya, K Saigenji, K Nakamura","doi":"10.1089/cbr.1994.9.171","DOIUrl":"https://doi.org/10.1089/cbr.1994.9.171","url":null,"abstract":"<p><p>The protein-bound polysaccharide of Coriolus versicolor QUEL (PS-K) expresses superoxide dismutase (SOD) mimicking activity. Examination was made of the suppressive effects of PS-K on cancer cell lines cultured in vitro. SOD activity of incorporated PS-K was 5.88 u/mg in LLC-WRC-256 (Walker 256 fibrosarcoma) cells and 4.73 u/mg in NRK-49F (rat normal kidney fibroblast) cells. SOD activity in both cell types was enhanced about 7-8 times that of the original PS-K. PS-K was not incorporated into H4-11-E or H4-11-E-C3 (rat hepatoma) cells. SOD activity of 1 mg/ml PS-K incubated with cell homogenates of LLC-WRC-256 cells for 6 hours increased from 0.68 u/mg to 1.35 u/mg. SOD activity of PS-K 1 mg/ml in 0.05 M phosphate buffer incubated with 50 microM NADPH increased from 0.68 u/mg. The consumption of NADPH at the same concentration was confirmed spectrophotometically by incubation with PS-K. The mechanism for the enhancement of SOD activity associated with PS-K is considered to be collaboration with NADPH as an electron donor in the cytoplasm of cancer cells whose SOD and coupling enzyme activities are significantly lower than in normal cells.</p>","PeriodicalId":79322,"journal":{"name":"Cancer biotherapy","volume":"9 2","pages":"171-8"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cbr.1994.9.171","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18812770","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":"Cancer biotherapy: the first year.","authors":"R K Oldham","doi":"10.1089/cbr.1994.9.179","DOIUrl":"https://doi.org/10.1089/cbr.1994.9.179","url":null,"abstract":"","PeriodicalId":79322,"journal":{"name":"Cancer biotherapy","volume":"9 3","pages":"179-81"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cbr.1994.9.179","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18820602","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":"Immunotherapy with low-dose interleukin-2 and anti-transforming growth factor-beta antibody in a murine tumor model.","authors":"X W Mao, J D Kettering, D S Gridley","doi":"10.1089/cbr.1994.9.317","DOIUrl":"https://doi.org/10.1089/cbr.1994.9.317","url":null,"abstract":"<p><p>The purpose of the present study was to evaluate the therapeutic efficacy of low-dose interleukin-2 (IL-2) alone or together with antibody against transforming growth factor-beta (TGF-beta) in a Herpes simplex virus Type 2-transformed (H238) fibrosarcoma model. BALB/c mice were inoculated subcutaneously (s.c.) with 5 x 10(5) H238 tumor cells in one or both hind thighs and treated with IL-2, anti-TGF-beta, or a combination of both agents. Nontreated tumor-bearing and normal animals served as controls. In the appropriate treatment groups, each mouse was given a total of 10(5) international units (i.u.) of IL-2 s.c. at one tumor implantation site and/or 1 microgram of anti-TGF-beta intraperitoneally (i.p.) over a period of 5 days beginning on the day of tumor cell implantation. No toxicity was noted during treatment. The slowest tumor growth was observed in mice with single tumors when treated with IL-2 or anti-TGF-beta alone, whereas combination treatment resulted in growth similar to that of untreated controls. However, in animals with two tumors, the tumor injected with IL-2 grew more rapidly than the untreated one. Spleen cell responsiveness to mitogenic stimulation was generally depressed in tumor-bearing mice compared to normal controls, but some differences were noted with treatment. In contrast, tumor presence induced striking splenomegaly and enhanced the chemiluminescent oxidative burst of phagocytic cells in the spleen. In the groups with a single tumor, plasma TGF-beta levels were similar to those of nontumor-bearing controls, however the concentrations were decreased in the animals with two tumors. These results show that IL-2 or anti-TGF-beta can slow progression of H238 tumors under certain conditions. However, combination of the two modalities proved to be of no benefit.</p>","PeriodicalId":79322,"journal":{"name":"Cancer biotherapy","volume":"9 4","pages":"317-27"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cbr.1994.9.317","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18723685","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":"Cytokines and the rational choice of immunological adjuvants.","authors":"A W Heath","doi":"10.1089/cbr.1994.9.1","DOIUrl":"https://doi.org/10.1089/cbr.1994.9.1","url":null,"abstract":"","PeriodicalId":79322,"journal":{"name":"Cancer biotherapy","volume":"9 1","pages":"1-6"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cbr.1994.9.1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18811595","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":"Oxidative stress relief for cancer-bearing hosts by the protein-bound polysaccharide of Coriolus versicolor QUEL with SOD mimicking activity.","authors":"Y Kobayashi, K Kariya, K Saigenji, K Nakamura","doi":"10.1089/cbr.1994.9.55","DOIUrl":"https://doi.org/10.1089/cbr.1994.9.55","url":null,"abstract":"<p><p>The protein-bound polysaccharide of Coriolus versicolor QUEL (PS-K) expresses the mimetic activity of superoxide dismutase (SOD). Human cancer patients usually suffer from oxidative stress (OS). Examination was made to determine the capacity of this drug with SOD mimetic activity for relieving OS. Rats transplanted with Walker 256 fibrosarcoma showed OS on day 12. After confirming high levels of OS on day 13, PS-K50 mg/kg was intraperitoneally administered, and prompt decrease in O2-release from RBC was noted. The drug ceased to have any effect 24 hours following the first inoculation. Average OS in human cancer patients was found twice that in healthy persons. In human cancer patients perorally administered PS-K3.0 g/day, OS decreased to the normal level one day after the initial administration. Plasma lipid peroxide (LPO) in cancer patients treated with PS-K for 28 days increased and withdrawal of the drug led to decreased LPO.</p>","PeriodicalId":79322,"journal":{"name":"Cancer biotherapy","volume":"9 1","pages":"55-62"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cbr.1994.9.55","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18811599","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}
D R Cook, I H Maxwell, L M Glode, F Maxwell, J O Stevens, M B Purner, E Wagner, D T Curiel, T J Curiel
{"title":"Gene therapy for B-cell lymphoma in a SCID mouse model using an immunoglobulin-regulated diphtheria toxin gene delivered by a novel adenovirus-polylysine conjugate.","authors":"D R Cook, I H Maxwell, L M Glode, F Maxwell, J O Stevens, M B Purner, E Wagner, D T Curiel, T J Curiel","doi":"10.1089/cbr.1994.9.131","DOIUrl":"https://doi.org/10.1089/cbr.1994.9.131","url":null,"abstract":"<p><p>Despite advances in conventional therapy, many lives continue to be lost to common forms of B-cell cancers, including leukemias, lymphomas and multiple myeloma. We propose a novel approach to therapy of such cancers using controlled expression of a diphtheria toxin gene (DT-A) to kill malignant cells. We have previously demonstrated selective killing of various cell types, in vitro and in vivo, by cell-specific, transcriptionally controlled expression of this gene. Organ-specific ablation in otherwise healthy transgenic mice has convincingly demonstrated the exquisite specificity achievable by this technique. In the studies now described, DT-A was delivered in vitro and in vivo using a novel gene delivery system employing DNA physically attached to the exterior of adenovirus. After demonstrating the efficacy of gene delivery to Epstein-Barr virus transformed human B-cells in vitro, in vivo work was performed using a SCID mouse model for B-cell lymphoma, in which protection against tumor was observed. The concepts of tissue-regulated toxin gene therapy, and this novel adenovirus gene delivery system are discussed.</p>","PeriodicalId":79322,"journal":{"name":"Cancer biotherapy","volume":"9 2","pages":"131-41"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cbr.1994.9.131","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18812767","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":"The clinical experience with interleukin-2 in cancer therapy.","authors":"R O Dillman","doi":"10.1089/cbr.1994.9.183","DOIUrl":"https://doi.org/10.1089/cbr.1994.9.183","url":null,"abstract":"<p><p>In May 1992, interleukin-2 (IL-2) was formally approved by the U.S. Food and Drug Administration for use in cancer treatment based on its activity in metastatic renal cell carcinoma. IL-2 alone or in combination with activated lymphocytes or other cytokines has significant anti-tumor activity against renal cell carcinoma and melanoma with response rates of 15-20%, some of which are quite durable. Limited anti-tumor effects have been noted in some patients with colorectal cancer and lymphoma. Too few patients have been studied to establish the level of activity in most other specific tumor types. The mechanism of this anti-tumor effect appears to be entirely mediated by the immunostimulatory effects of IL-2. Toxicities are dose related, but are substantial and similar regardless of the schedule of administration. Randomized trials have failed to establish (1) the superiority of high-dose bolus over continuous infusion IL-2, (2) the superiority of IL-2 plus interferon over IL-2 alone, or (3) the superiority of IL-2 plus LAK cells versus IL-2 alone. Further investigation is needed to determine the optimum dose and schedule from the standpoint of cost:benefit and risk:benefit, and to determine the role of IL-2 in the therapy of other malignant diseases.</p>","PeriodicalId":79322,"journal":{"name":"Cancer biotherapy","volume":"9 3","pages":"183-209"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cbr.1994.9.183","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18820603","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":"Leukemia after chemotherapy for cancer.","authors":"M R Chasen, G Falkson","doi":"10.1089/cbr.1993.8.115","DOIUrl":"https://doi.org/10.1089/cbr.1993.8.115","url":null,"abstract":"","PeriodicalId":79322,"journal":{"name":"Cancer biotherapy","volume":"8 2","pages":"115-22"},"PeriodicalIF":0.0,"publicationDate":"1993-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cbr.1993.8.115","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18805273","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}