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Cancer Immunology, Immunotherapy : CII 1992Picibanil (OK432), an extract from streptococci, has been widely utilized to treat malignant ascites and pleural effusions. The antitumor mechanism is believed to...
Picibanil (OK432), an extract from streptococci, has been widely utilized to treat malignant ascites and pleural effusions. The antitumor mechanism is believed to include complement-mediated neutrophil activation. Employing a flow-cytometric analysis of actin polymerization as an indicator of cell activation as well as a tumor proliferation assay, we have found that monocyte-derived neutrophil-activating factors were involved in OK432-induced neutrophil activation as well as antitumor activity. OK432-stimulated (0.1 KE/ml; 0.01 mg/ml) monocyte supernatants (OKMS) induced neutrophil actin polymerization and chemotaxis. OKMS were responsible for neutrophil-mediated inhibition of human leukemic (CEM) cell proliferation and stimulated neutrophils to produce superoxide in the presence of CEM leukemic cells at an effector/target ratio higher than 20/1. In contrast, OK432 alone, OK432-stimulated lymphocyte supernatants, or OK432-stimulated neutrophil supernatants had no effect on neutrophil activation or suppression of tumor cell proliferation. OK432 in combination with mononuclear cells also had no effect on the inhibition of CEM cell proliferation. Pretreatment of OKMS at 56 degrees C for 30 min did not affect its ability to activate neutrophils, implying that complement activation is not responsible for the neutrophil activation. Supernatants from OK432-stimulated mononuclear cells, as determined by enzyme-linked immunosorbent assays and radioimmunoassays, contained high levels of interleukin-8 (IL-8; 1567 +/- 145 pg/ml) and tumor necrosis factor (TNF alpha; 2105 +/- 152 pg/ml), low levels of leukotriene B4 (800 +/- 45 pg/ml) and IL-1 beta (180 +/- 22 pg/ml), but interferon gamma was not detectable. IL-1 beta, IL-8, and TNF alpha transcripts, undetectable in untreated monocytes, increased significantly after 30-60 min exposure to OK432. These results suggest that neutrophil-activating factors from monocytes or resident macrophages may play an important role in the OK432-induced neutrophil activation and antitumor activity.
Topics: Adult; Chemotaxis, Leukocyte; Humans; Interleukin-8; Leukemia, Experimental; Lymphocyte Activation; Neutrophils; Picibanil; Tumor Cells, Cultured
PubMed: 1511463
DOI: 10.1007/BF01789335 -
Hong Kong Medical Journal = Xianggang... Apr 2012Chylothorax is a rare congenital condition associated with significant perinatal mortality and morbidity. Previous treatments with repeated thoracocentesis or... (Review)
Review
Chylothorax is a rare congenital condition associated with significant perinatal mortality and morbidity. Previous treatments with repeated thoracocentesis or thoracoamniotic shunting were technically demanding, and associated with significant procedure-related complications and neonatal complications. Here we report the first successful case in Hong Kong treated by a simple and effective intervention, namely pleurodesis with OK-432, in a fetus presenting at 20 weeks of gestation with bilateral pleural effusion.
Topics: Chylothorax; Female; Fetal Diseases; Humans; Picibanil; Pleurodesis; Pregnancy
PubMed: 22477741
DOI: No ID Found -
The Medical Journal of Malaysia Oct 2019Cervico facial cystic hygroma and tongue lymphagioma is rare representative of spectrum of lymphatic malformations. Conservative management with sclerosants alone has...
Cervico facial cystic hygroma and tongue lymphagioma is rare representative of spectrum of lymphatic malformations. Conservative management with sclerosants alone has proven to be successful. However, sudden enlargement of these cervico facial lymphangiomas leads to catastrophic airway obstruction leading to debility in feeding and speech. Therefore, surgery is indicated in such case to prevent such a catastrophic problem. We report here the case of a 3-yearold boy with cervico facial hygroma involving the tongue. We successfully treated him with a combination of surgery and OK432 injection.
Topics: Antineoplastic Agents; Child, Preschool; Decision Making; Diagnosis, Differential; Glossectomy; Head and Neck Neoplasms; Humans; Injections; Lymphangioma, Cystic; Magnetic Resonance Imaging; Male; Picibanil; Therapy, Computer-Assisted; Tracheostomy
PubMed: 31649229
DOI: No ID Found -
Journal of Korean Medical Science Sep 2010Dendritic cells (DCs) are potent antigen-presenting cells. OK432 (Picibanil) was introduced as a potent stimulator of DC maturation in combination with...
Dendritic cells (DCs) are potent antigen-presenting cells. OK432 (Picibanil) was introduced as a potent stimulator of DC maturation in combination with prostaglandin-E(2) and interferon-alpha. We compared the efficacy of a DC-prostate cancer vaccine using early-mature DCs stimulated with OK432, PGE2 and INF-alpha (OPA) with that of vaccines using other methods. On days 3 or 7 of DC culture, TNF-alpha (T), TNF-alpha and LPS (TL) or OPA were employed as maturation stimulators. DU145 cells subjected to heat stress were hybridized with mature DCs using polyethyleneglycol. T cells were sensitized by the hybrids, and their proliferative and cytokine secretion activities and cytotoxicity were measured. The yields of early-mature DCs were higher, compared to yields at the conventional maturation time (P<0.05). In the early maturation setting, the mean fusion ratios, calculated from the fraction of dual-positive cells, were 13.3%, 18.6%, and 39.9%, respectively (P=0.051) in the T only, TL, and OPA-treated groups. The function of cytotoxic T cells, which were sensitized with the hybrids containing DCs matured early with OPA, was superior to that using other methods. The antitumor effects of DC-DU145 hybrids generated with DCs subjected to early maturation with the OPA may be superior to that of the hybrids using conventional maturation methods.
Topics: Cancer Vaccines; Cell Line, Tumor; Dendritic Cells; Dinoprostone; Humans; Immunologic Factors; Interferon-alpha; Lipopolysaccharides; Male; Neoplasms, Hormone-Dependent; Phenotype; Picibanil; Prostatic Neoplasms; T-Lymphocytes, Cytotoxic
PubMed: 20808670
DOI: 10.3346/jkms.2010.25.9.1284 -
Archives of Disease in Childhood Apr 2000Over a period of seven years, 15 patients (aged from birth to 15 years; median 22 months) with lymphangioma were treated with OK-432; they received a mean of three...
Over a period of seven years, 15 patients (aged from birth to 15 years; median 22 months) with lymphangioma were treated with OK-432; they received a mean of three injections each. Ten received OK-432 as first line treatment; five were treated after surgery (three had a residual lymphangioma after incomplete removal and two had a late recurrence). OK-432 proved to be effective for primitive as well as for residual and recurrent lymphangioma. Seven cases were macrocystic; complete regression was obtained in all. Five cases were microcystic: two had more than 50% regression, and three less than 50%. Three cases were mixed, with both large and microscopic cysts: one had more than 50% regression, and two less than 50%. These last two cases underwent surgery after the sclerosing treatment. The results obtained were excellent in 100% of macrocystic cases; a shrinkage in size was obtained in all microcystic cases. OK-432 is therefore proposed as a first line option for treatment of lymphangiomas.
Topics: Adolescent; Antineoplastic Agents; Child; Child, Preschool; Head and Neck Neoplasms; Humans; Infant; Infant, Newborn; Lymphangioma; Picibanil; Radiography; Sclerotherapy
PubMed: 10735841
DOI: 10.1136/adc.82.4.316 -
Cancer Immunology, Immunotherapy : CII May 1997The microbial immunostimulant OK-432 has been studied intensively in preclinical systems and has shown promise as an anticancer agent in trials that have been conducted... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
The microbial immunostimulant OK-432 has been studied intensively in preclinical systems and has shown promise as an anticancer agent in trials that have been conducted over the past 20 years in Japan. To date, no systematic dose response evaluation of this agent has defined its dose-limiting toxicity or immunobiological activity. A phase IA study has been conducted in 25 patients with metastatic cancer at the University of Pittsburgh Cancer Institute Melanoma Center, establishing 30 KE as the maximal tolerable dosage, on the basis of cutaneous reactions. Subsequently, 48 patients with resected high-risk melanoma participated in a phase IB study of OK-432. This study has evaluated the immunomodulatory activity of OK-432 at five dosages ranging from 1 KE to 20 KE, administered ID twice weekly for 3 months. A formal analysis of the treated population in comparison to the randomized control group has been conducted, and profound immunological effects have been defined in the group of patients treated with OK-432. Patients who participated in this trial had a significant depression of OK-432-inducible cytokine production (interleukin-1 beta, interferon gamma, and tumor necrosis factor alpha) at baseline. Treatment with OK-432 reversed this deficit for interferon gamma (IFN gamma) production in a dose-dependent manner, and mitigated the inhibition for interleukin-1 (IL-1) across all dosage groups. The impact of OK-432 upon other immunological functions of the treated cohorts is more variable, with durable suppression of mononuclear cell superoxide production, and in vitro cytotoxicity to tumor. Immunological characteristics of the entire cohort demonstrate a strong and significant correlation of elevated blood CD16+ cell counts and natural killer activity with early tumor progression and death due to melanoma. Favorable prognosis is associated with monocyte capacity to produce tumor necrosis factor (TNF), and polymorphonuclear leukocyte formylmethionyl-leucylphenylalanine-inducible superoxide release. This study reveals several new immunological correlates of tumor progression and lethal outcome in resected high-risk melanoma. It demonstrates that the depressed IL-1, TNF, and IFN gamma release associated with melanoma may be mitigated by treatment with OK-432. This study has defined treatment and dose response patterns of immunomodulation associated with one of the most complex immunological agents yet evaluated in phase IB trials, in a well-defined population of high-risk patients with resected melanoma.
Topics: Adjuvants, Immunologic; Antineoplastic Agents; Cytotoxicity, Immunologic; Female; Humans; Male; Melanoma; Picibanil
PubMed: 9191873
DOI: 10.1007/s002620050366 -
Fetal Diagnosis and Therapy 2015Primary fetal hydrothorax (PFHT) is an uncommon condition with an estimated prevalence of 1 in 10,000/15,000 pregnancies. Therapeutic interventions include...
BACKGROUND
Primary fetal hydrothorax (PFHT) is an uncommon condition with an estimated prevalence of 1 in 10,000/15,000 pregnancies. Therapeutic interventions include thoracocentesis, thoraco-amniotic shunting (TAS), and pleurodesis using OK-432.
METHODS
A review of the literature was performed to identify all cases of PFHT treated with TAS and OK-432. All cases of PFHT referred to the Fetal Maternal Unit at Royal Prince Alfred Hospital between 2002 and 2012 were retrospectively reviewed. In the cohort of fetuses treated with OK-432, the main perinatal outcomes evaluated were termination of pregnancy, live birth, neonatal death, and fetal death in utero. Secondary outcomes included gestational age (GA) at diagnosis, GA at treatment, GA at resolution, birth weight, and GA at birth. The development of the children was screened using the Ages and Stages Questionnaires, Version 3 (ASQ-3, 2009).
RESULTS
Primary hydrothorax was diagnosed in 31 fetuses, of which 14 had treatment with OK-432. One pregnancy terminated after treatment with OK-432. Survival was 85% (11/13): 100% in fetuses treated with OK-432 without hydrops, and 78% in those treated with hydrops. This compares well to the cases of TAS in the literature with an average survival of 63%: 85% in fetuses without hydrops and 55% with hydrops. The mean GA at birth was 36(+4) weeks and mean birth weight 3,007 g. Eight of the 9 children screened with ASQ-3 scored well within the normal range.
CONCLUSION
OK-432 appears to be a valid treatment option in fetuses with PFHT, particularly in those diagnosed at early GAs.
Topics: Female; Fetal Diseases; Gestational Age; Humans; Hydrothorax; Male; Picibanil; Pregnancy; Prognosis; Retrospective Studies; Treatment Outcome; Ultrasonography, Prenatal
PubMed: 25721226
DOI: 10.1159/000363651 -
Journal of Cardiothoracic Surgery Jan 2024Pleurodesis is often performed for air leaks; however, the ideal materials and timing of the procedure remain controversial. We investigated the efficacy of pleurodesis...
BACKGROUND
Pleurodesis is often performed for air leaks; however, the ideal materials and timing of the procedure remain controversial. We investigated the efficacy of pleurodesis using different materials and timing.
METHODS
We retrospectively reviewed 913 consecutive patients who underwent segmentectomy or lobectomy for non-small cell lung cancer between 2014 and 2021. Pleurodesis efficacy was assessed on the day of chest tube removal.
RESULTS
Eighty-six patients (9%) underwent pleurodesis for postoperative air leaks. Pleurodesis was performed on a median of postoperative day (POD) 5. Talc was the most frequently used material (n = 52, 60%), followed by autologous blood patches (n = 20, 23%), OK-432 (n = 12, 14%), and others (n = 2, 2%). No difference existed in the number of days from initial pleurodesis to chest tube removal among the three groups (talc, 3 days; autologous blood patch, 3 days; OK-432, 2 days; P = 0.55). No difference in patient background, except for sex, was observed between patients who underwent pleurodesis within 4 PODs and those who underwent pleurodesis on POD 5 or later. Drainage time was significantly shorter in patients who underwent pleurodesis within 4 PODs (median, 7 vs. 9 days; P = 0.004).
CONCLUSIONS
The efficacies of autologous blood patch, talc, and OK-432 would be considered comparable and early postoperative pleurodesis could shorten drainage time. Prospective studies are required.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Talc; Pleurodesis; Picibanil; Retrospective Studies; Pneumonectomy; Lung
PubMed: 38167171
DOI: 10.1186/s13019-023-02444-6 -
Journal of the Formosan Medical... May 2014Prolonged air leak is the most common complication after thoracoscopic operation for primary spontaneous pneumothorax (PSP), and the role of chemical pleurodesis in...
BACKGROUND/PURPOSE
Prolonged air leak is the most common complication after thoracoscopic operation for primary spontaneous pneumothorax (PSP), and the role of chemical pleurodesis in treating air leaks remains unclear. This study evaluated the safety and efficacy of chemical pleurodesis with a comparison between minocycline and OK-432.
METHODS
Between 1994 and 2011, 1083 PSP patients were treated by thoracoscopic operation. After the operation, patients with persistent air leak for 3 days or more were managed by minocycline or OK-432 pleurodesis. The demographic and outcome data for these patients were collected by retrospective chart review.
RESULTS
Seventy-nine patients (7.3%) with prolonged air leak after thoracoscopy underwent minocycline pleurodesis (60 patients) or OK-432 pleurodesis (19 patients) as the primary treatment. The primary success rate was 63% (38/60) for minocycline pleurodesis and 95% (18/19) for OK-432 pleurodesis (p = 0.009). Postpleurodesis pain was common and comparable between the two groups. No major complications were noted after a total of 121 treatments. Patients undergoing primary OK-432 pleurodesis had shorter durations of postpleurodesis chest drainage (mean 8.5 vs. 2.3 days; p < 0.001) and postoperative hospital stay (mean 11.9 vs. 6.8 days; p < 0.001) than those undergoing primary minocycline pleurodesis. After a median follow-up of 16 months, recurrence was noted in one patient in the OK-432 group and none in the minocycline group. Long-term pulmonary function in the two groups was comparable.
CONCLUSION
Chemical pleurodesis using OK-432 or minocycline is safe and convenient for prolonged air leak after thoracoscopic treatment for PSP. Our experience suggested that OK-432 may be more effective than minocycline in reducing air leak.
Topics: Adult; Female; Humans; Male; Minocycline; Picibanil; Pleurodesis; Pneumothorax; Postoperative Complications; Retrospective Studies; Thoracic Surgery, Video-Assisted
PubMed: 24746114
DOI: 10.1016/j.jfma.2012.12.016 -
European Journal of Immunology Apr 2013Cancer vaccines have yet to yield clinical benefit, despite the measurable induction of humoral and cellular immune responses. As immunosuppression by CD4(+) CD25(+)...
Cancer vaccines have yet to yield clinical benefit, despite the measurable induction of humoral and cellular immune responses. As immunosuppression by CD4(+) CD25(+) regulatory T (Treg) cells has been linked to the failure of cancer immunotherapy, blocking suppression is therefore critical for successful clinical strategies. Here, we addressed whether a lyophilized preparation of Streptococcus pyogenes (OK-432), which stimulates Toll-like receptors, could overcome Treg-cell suppression of CD4(+) T-cell responses in vitro and in vivo. OK-432 significantly enhanced in vitro proliferation of CD4(+) effector T cells by blocking Treg-cell suppression and this blocking effect depended on IL-12 derived from antigen-presenting cells. Direct administration of OK-432 into tumor-associated exudate fluids resulted in a reduction of the frequency and suppressive function of CD4(+) CD25(+) Foxp3(+) Treg cells. Furthermore, when OK-432 was used as an adjuvant of vaccination with HER2 and NY-ESO-1 for esophageal cancer patients, NY-ESO-1-specific CD4(+) T-cell precursors were activated, and NY-ESO-1-specific CD4(+) T cells were detected within the effector/memory T-cell population. CD4(+) T-cell clones from these patients had high-affinity TCRs and recognized naturally processed NY-ESO-1 protein presented by dendritic cells. OK-432 therefore inhibits Treg-cell function and contributes to the activation of high-avidity tumor antigen-specific naive T-cell precursors.
Topics: Antigen-Presenting Cells; Antigens, Neoplasm; CD4 Antigens; Cancer Vaccines; Exudates and Transudates; Humans; Immunosuppression Therapy; Interleukin-12; Interleukin-2 Receptor alpha Subunit; Membrane Proteins; Neoplasms; Picibanil; Streptococcus pyogenes; T-Lymphocytes, Regulatory
PubMed: 23436617
DOI: 10.1002/eji.201242800