title: The past, the present and future of the OK-432 therapy for patients with malignant effusions.
abstract: For the past 20 years, our group has treated over 400 cases of malignant effusion by the intraperitoneal injection of streptococcal preparation OK432 (OK-432 therapy) and has investigated extensively the antitumor mechanisms of this therapy. Prospective clinical data has demonstrated that the OK-432 therapy induced a definite reduction of the effusions in around 60% (responders) of cases and significantly prolonged the survival time in patients who responded well. In addition, a definite reduction of original tumor mass volume was found in around 20% of cases. We have shown that OK432-induced neutrophils, lymphocytes, and probably macrophages may play an important role in tumor cell destruction in ascites. Tumor necrosis factor alpha (TNF-alpha)-induced CD11b/CD18 expression on leukocytes and interferon-gamma (IFN-gamma)-induced ICAM-1 expression on tumor cells may play an important role in leukocyte-mediated tumor destruction. It has also been shown that OK-432 induces various cytokines, such as TNF-alpha, TNF-beta, IFN-alpha IFN-gamma, interleukin-1 (IL-1), IL-2, IL-6, IL-12, tumor growth inhibitory factor(s) (TGIF), and possibly unknown apoptosis-inducing factor(s). Some of these cytokines have been adduced as representing the antitumor activity. These data suggest that two pathways of antitumor activity, i.e., cell-mediated and cytokine-mediated, can be induced simultaneously in the peritoneal cavity. OK-432 therapy may be valuable in the management of patients with malignant effusions. Future clinical and basic research should contribute to further progress in OK-432 therapy.
authors.affiliation: Department of Surgery, Saga Medical School, Japan. Katano@post.saga-med.acjp
authors.forename: M
authors.initials: M
authors.lastname: Katano
authors.forename: T
authors.initials: T
authors.lastname: Morisaki
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001202:Ascitic Fluid / Q000000981:diagnostic imaging; D005544:Forecasting; D006801:Humans; D009504:Neutrophils / Q000276:immunology; D010844:Picibanil / Q000627:therapeutic use*; D016066:Pleural Effusion, Malignant; D011859:Radiography; D015996:Survival Rate; D016896:Treatment Outcome; D014463:Ultrasonography
chemical_list: D000970:Antineoplastic Agents; D010844:Picibanil