-
Anticancer Research 2004OK-432 (Picibanil), a streptococcal preparation with potent biological response modifying activities, was approved in Japan as an anticancer agent in 1975. In the... (Review)
Review
OK-432 (Picibanil), a streptococcal preparation with potent biological response modifying activities, was approved in Japan as an anticancer agent in 1975. In the ensuing 30 years, since then, a significant amount of data, including clinical as well as experimental studies, has been accumulated. OK-432 has been reported to induce various cytokines, activate immunological cells and thus augment anticancer immunity. Recently, the interrelation between innate immunity and adaptive immunity has become clear and it was reported that OK-432 acts, at least in part, via Toll-like receptor (TLR) 4-MD2 signaling pathway. In addition, dendritic cells (DCs) are considered to play a pivotal role in immunological response and it is reported that OK-432 induced maturation of DCs both in vitro and in vivo. These results suggest that OK-432 is a useful adjuvant in DC-based anticancer immunotherapy. Clinical studies of DC therapy with OK-432 are under way.
Topics: Animals; Antineoplastic Agents; Dendritic Cells; Humans; Immunotherapy, Adoptive; Picibanil
PubMed: 15515424
DOI: No ID Found -
Annals of Medicine and Surgery (2012) Sep 2022Congenital cystic lymphangiomas (CCL) or lymphatic malformations (LMs) are benign malformations due to a developmental disorder of lymphatic vessels. Besides surgical...
INTRODUCTION
Congenital cystic lymphangiomas (CCL) or lymphatic malformations (LMs) are benign malformations due to a developmental disorder of lymphatic vessels. Besides surgical excision, sclerosant therapy of these lesions by intracavitary injection of OK-432 (Picibanil®), a lyophilized mixture of group A Streptococcus pyogenes, is a common therapeutical option.
METHODS
In a single center retrospective study we analyzed 37 consecutive patients (30 children, 3 adolescents and 4 adults) who were diagnosed with lymphangioma and subsequently treated with OK-432 (Picibanil®) in a general hospital between October 2000 and November 2021.
RESULTS
The median follow-up period was 2.5 months (range 0.7-56.7 months). The lymphangiomas were localized in the head and neck region (n = 25), the thorax/abdomen (n = 6) and extremities (n = 6). The majority of patients had 1 injection with OK-432 (n = 28), five patients had 2 injections, three patients had 3 injections and one patient had more than 3 injections. The most common complications were swelling (89%), fever (81%), redness at the injection site (81%) and pain (73%). The response to therapy was excellent or good in 32 patients (86.4%), 2 patients had a medium response and 3 patients did not show any response. The clinical reaction after the instillation of OK-432 is not predictive for the quality of outcome.
CONCLUSION
The application of Picibanil is safe and without serious side effects. Parents and patients prefer local sclerotherapy versus surgery as it has less complications. We therefore suggest that Picibanil sclerotherapy should be the first-line treatment for macrocystic and mixed type lymphangiomas.
PubMed: 36147081
DOI: 10.1016/j.amsu.2022.104531 -
Gynecology and Minimally Invasive... 2021This is a case report of a uterine cancer with the International Federation of Gynecology and Obstetrics staging 3c2 with the initial clinical presentation of...
This is a case report of a uterine cancer with the International Federation of Gynecology and Obstetrics staging 3c2 with the initial clinical presentation of postmenopausal vaginal bleeding in August 2015. Endometrium biopsy showed invasive nests of poorly differentiated grade 3 endometrioid adenocarcinoma. The patient received robotic surgery including total hysterectomy, bilateral salpingo-oophorectomy, bilateral pelvic lymph node dissection, para-aortic lymph node dissection, and washing cytology. The final pathology showed an endometrioid carcinoma with myometrium invasion up to 85% and para-aortic and pelvic lymph nodes invasion. The patient received six courses of adjuvant chemotherapy (paclitaxel and carboplatin) with concurrent chemoradiotherapy after the surgery. Later, immunotherapy with Picibanil (OK-432) and interleukin-2 (IL-2) was given, and cancer did not recur for 34 months until tumor recurrence at the liver dome and bilateral lung was noted by positron-emission tomography scan in July 2018. The patient received laparoscopic surgery for intra-abdominal tumor excision in December 2018, and the tumor found extended to the right diaphragm, liver surface, omentum, bilateral flank to pelvic peritoneum, Douglas pouch, and upper rectum. We continued the immunotherapy with OK-432, IL-2, Aldara cream (imiquimod), and later on, virotherapy (human papillomavirus vaccine). The immune risk profiles showed T-cells' proliferation and alteration of the Th1/Th2 activation after immunotherapy and virotherapy. Proctectomy with colon-anal anastomosis and cytoreduction surgery with hyperthermic intraperitoneal chemotherapy (HIPEC) (doxorubicin and paclitaxel) was performed in January 2019. After the surgery, the patient received chemotherapy (topotecan, paclitaxel, lipodox, and carboplatin) and continued the immunotherapy. The immune risk profiles showed CD4, CD4/CD8 increase after HIPEC and immunotherapy. The patient continued the therapy until May 2020.
PubMed: 34485069
DOI: 10.4103/GMIT.GMIT_153_20 -
Journal of Nanobiotechnology Nov 2023To investigate the efficacy of an injectable hydrogel loaded with lysed OK-432 (lyOK-432) and doxorubicin (DOX) for residual liver cancer after incomplete radiofrequency...
OBJECTIVE
To investigate the efficacy of an injectable hydrogel loaded with lysed OK-432 (lyOK-432) and doxorubicin (DOX) for residual liver cancer after incomplete radiofrequency ablation (iRFA) of hepatocellular carcinoma (HCC), and explore the underlying mechanism.
MATERIALS AND METHODS
The effect of OK-432 and lyOK-432 was compared in activating dendritic cells (DCs). RADA16-I (R) peptide was dissolved in a mixture of lyOK-432 (O) and DOX (D) to develop an ROD hydrogel. The characteristics of ROD hydrogel were evaluated. Tumor response and mice survival were measured after different treatments. The number of immune cells and cytokine levels were measured, and the activation of cGAS/STING/IFN-I signaling pathway in DC was evaluated both in vitro and in vivo.
RESULTS
LyOK-432 was more effective than OK-432 in promoting DC maturation and activating the IFN-I pathway. ROD was an injectable hydrogel for effectively loading lyOK-432 and DOX, and presented the controlled-release property. ROD treatment achieved the highest tumor necrosis rate (p < 0.001) and the longest survival time (p < 0.001) compared with the other therapies. The ROD group also displayed the highest percentages of DCs, CD4 T cells and CD8 T cells (p < 0.001), the lowest level of Treg cells (p < 0.001), and the highest expression levels of IFN-γ and TNF-α (p < 0.001) compared with the other groups. The expression levels of pSTING, pIRF3, and IFN-β in DCs were obviously higher after treatment of lyOK-432 in combination with DOX than the other therapies. The surviving mice in the ROD group showed a growth inhibition of rechallenged subcutaneous tumor.
CONCLUSION
The novel ROD peptide hydrogel induced an antitumor immunity by activating the STING pathway, which was effective for treating residual liver cancer after iRFA of HCC.
Topics: Animals; Mice; Picibanil; Liver Neoplasms; Carcinoma, Hepatocellular; Hydrogels; CD8-Positive T-Lymphocytes; Doxorubicin; Cytokines; Radiofrequency Ablation
PubMed: 37919724
DOI: 10.1186/s12951-023-02170-0 -
The British Journal of Ophthalmology Jan 2000
Topics: Adult; Female; Humans; Lymphangioma; Orbital Neoplasms; Picibanil; Sclerosing Solutions; Sclerotherapy; Treatment Failure
PubMed: 10611113
DOI: 10.1136/bjo.84.1.124b -
Oncoimmunology Aug 2013Toll-like receptors (TLRs) have long been known for their ability to initiate innate immune responses upon exposure to conserved microbial components such as... (Review)
Review
Toll-like receptors (TLRs) have long been known for their ability to initiate innate immune responses upon exposure to conserved microbial components such as lipopolysaccharide (LPS) and double-stranded RNA. More recently, this family of pattern recognition receptors has been attributed a critical role in the elicitation of anticancer immune responses, raising interest in the development of immunochemotherapeutic regimens based on natural or synthetic TLR agonists. In spite of such an intense wave of preclinical and clinical investigation, only three TLR agonists are currently licensed by FDA for use in cancer patients: bacillus Calmette-Guérin (BCG), an attenuated strain of that operates as a mixed TLR2/TLR4 agonist; monophosphoryl lipid A (MPL), a derivative of that functions as a potent agonist of TLR4; and imiquimod, a synthetic imidazoquinoline that activates TLR7. One year ago, in the August and September issues of , we described the main biological features of TLRs and discussed the progress of clinical studies evaluating the safety and therapeutic potential of TLR agonists in cancer patients. Here, we summarize the latest developments in this exciting area of research, focusing on preclinical studies that have been published during the last 13 mo and clinical trials launched in the same period to investigate the antineoplastic activity of TLR agonists.
PubMed: 24083080
DOI: 10.4161/onci.25238 -
Journal of the Formosan Medical... Dec 2013Pneumothorax is defined as the presence of air in the pleural cavity. Spontaneous pneumothorax, occurring without antecedent traumatic or iatrogenic cause, is... (Review)
Review
Pneumothorax is defined as the presence of air in the pleural cavity. Spontaneous pneumothorax, occurring without antecedent traumatic or iatrogenic cause, is sub-divided into primary and secondary. The severity of pneumothorax could be varied from asymptomatic to hemodynamically compromised. Optimal management of this benign disease has been a matter of debate. In addition to evacuating air from the pleural space by simple aspiration or chest tube drainage, the management of spontaneous pneumothorax also focused on ceasing air leakage and preventing recurrences by surgical intervention or chemical pleurodesis. Chemical pleurodesis is a procedure to achieve symphysis between the two layers of pleura by sclerosing agents. In the current practice guidelines, chemical pleurodesis is reserved for patients unable or unwilling to receive surgery. Recent researches have found that chemical pleurodesis is also safe and effective in preventing pneumothorax recurrence in patients with the first episode of spontaneous pneumothorax or after thoracoscopic surgery and treating persistent air leakage after thoracoscopic surgery. In this article we aimed at exploring the role of chemical pleurodesis for spontaneous pneumothorax, including ceasing air leakage and preventing recurrence. The indications, choice of sclerosants, safety, effects, and possible side effects or complications of chemical pleurodesis are also reviewed here.
Topics: Anti-Bacterial Agents; Anti-Infective Agents, Local; Antibiotics, Antineoplastic; Antineoplastic Agents; Bleomycin; Humans; Minocycline; Picibanil; Pleurodesis; Pneumothorax; Povidone-Iodine; Secondary Prevention; Talc; Tetracycline
PubMed: 24268613
DOI: 10.1016/j.jfma.2013.10.016 -
Journal of Cardiothoracic Surgery Jun 2019Postoperative pericardial adhesions are considered a risk factor for redo cardiac surgery. Several large- and medium-size animal models of pericardial adhesions have...
BACKGROUND
Postoperative pericardial adhesions are considered a risk factor for redo cardiac surgery. Several large- and medium-size animal models of pericardial adhesions have been reported, but small animal models for investigating the development of anti-adhesion materials and molecular mechanisms of this condition are lacking. In this study, we aimed to establish a simple mouse model of pericardial adhesions to address this gap.
METHODS
We administered blood, minocycline, picibanil, and talc into the murine pericardial cavity via one-shot injection. Micro-computed tomography analyses of contrast agent-injected mice were carried out for methodological evaluation. We investigated various dosages and treatment durations for molecules identified to be inducers of pericardial adhesion. The adhesive grade was quantified by scoring the strength and volume of adhesion tissues at sacrificed time points. Histological staining with hematoxylin and eosin and Masson's trichrome, and immunostaining for F4/80 or αSMA was performed to investigate the structural features of pericardial adhesions, and pathological features of the pericardial adhesion tissue were compared with human clinical specimens.
RESULTS
Administration of talc resulted in the most extensive pericardial adhesions. Micro-computed tomography imaging data confirmed that accurate injection into the pericardial cavity was achieved. We found the optimal condition for the formation of strong pericardial adhesions to be injection of 2.5 mg/g talc for 2 weeks. Furthermore, histological analysis showed that talc administration led to an invasion of myofibroblasts and macrophages in the pericardial cavity and epicardium, consistent with pathological findings in patients with left ventricular assistive devices.
CONCLUSIONS
We successfully established a simple mouse model of talc-induced pericardial adhesions, which mimics human pathology and could contribute to solving the clinical issues related to pericardial adhesions.
Topics: Animals; Cardiac Surgical Procedures; Disease Models, Animal; Male; Mice; Mice, Inbred C57BL; Pericardium; Postoperative Complications; Tissue Adhesions; X-Ray Microtomography
PubMed: 31253183
DOI: 10.1186/s13019-019-0940-9 -
Ultrasonography (Seoul, Korea) Apr 2014Surgical excision has traditionally been the treatment of choice for benign non-thyroid cystic neck masses, including lymphatic malformation, ranula, branchial cleft... (Review)
Review
Surgical excision has traditionally been the treatment of choice for benign non-thyroid cystic neck masses, including lymphatic malformation, ranula, branchial cleft cyst, thyroglossal duct cyst, and parathyroid cyst. However, there is a tendency toward recurrence after surgery, and surgery may be accompanied by complications, including nerve injuries, vascular injuries, and scar formation. Ultrasound-guided sclerotherapy using various agents has been challenged and successfully applied as an alternative treatment for benign non-thyroid cystic neck masses. This report reviews the available sclerosing agents and describes the applications of sclerotherapy to the treatment of benign cystic masses in the neck.
PubMed: 24936500
DOI: 10.14366/usg.13026 -
Journal of Cerebral Blood Flow and... Jun 2024Perinatal infection or inflammation are associated with adverse neurodevelopmental effects and cardiovascular impairments in preterm infants. Most preclinical studies...
Perinatal infection or inflammation are associated with adverse neurodevelopmental effects and cardiovascular impairments in preterm infants. Most preclinical studies have examined the effects of gram-negative bacterial inflammation on the developing brain, although gram-positive bacterial infections are a major contributor to adverse outcomes. Killed Su-strain group 3 A streptococcus pyogenes (Picibanil, OK-432) is being used for pleurodesis in fetal hydrothorax/chylothorax. We therefore examined the neural and cardiovascular effects of clinically relevant intra-plural infusions of Picibanil. Chronically instrumented preterm (0.7 gestation) fetal sheep received an intra-pleural injection of low-dose (0.1 mg, n = 8) or high-dose (1 mg, n = 8) Picibanil or saline-vehicle (n = 8). Fetal brains were collected for histology one-week after injection. Picibanil exposure was associated with sustained diffuse white matter inflammation and loss of immature and mature oligodendrocytes and subcortical neurons, and associated loss of EEG power. These neural effects were not dose-dependent. Picibanil was also associated with acute changes in heart rate and attenuation of the maturational increase in mean arterial pressure. Even a single exposure to a low-dose gram-positive bacterial-mediated inflammation during the antenatal period is associated with prolonged changes in vascular and neural function.
Topics: Animals; Sheep; Female; Inflammation; Pregnancy; Brain; Streptococcus pyogenes; Fetus; Heart Rate; Neurons; Electroencephalography
PubMed: 37824725
DOI: 10.1177/0271678X231197380