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Biomedicine & Pharmacotherapy =... Oct 2023Radiofrequency ablation (RFA) often results in incomplete ablation for medium-to-large and irregular tumors. To solve this clinical problem, we proposed a new treatment...
BACKGROUND AND AIMS
Radiofrequency ablation (RFA) often results in incomplete ablation for medium-to-large and irregular tumors. To solve this clinical problem, we proposed a new treatment strategy of OK-432 in combination with an anti-programmed cell death protein 1 (αPD-1) antibody for residual tumors after incomplete RFA (iRFA) of hepatocellular carcinoma (HCC).
APPROACH AND RESULTS
The effect of OK-432 on immature dendritic cells (iDCs) was evaluated in vitro. A CCK-8 kit and ELISPOT were used to assess the killing effect of OK-432-induced CD8 T cells in combination with an αPD-1 antibody on Hepa1-6 cells. We found that OK-432 significantly increased the maturation level of DCs, and OK-432-induced CD8 T cells in combination with αPD-1 antibody significantly enhanced the function of CD8 T cells. In the in vivo experiment, HCC model mice were treated with (1) pseudo iRFA + phosphate-buffered saline (PBS); (2) iRFA + PBS; (3) iRFA + OK-432; (4) iRFA + αPD-1; or (5) iRFA + OK-432 + αPD-1. We found that the combined therapy of OK-432 with αPD-1 antibody significantly increased the infiltration and function of CD8 T cells and significantly decreased the number of FoxP3 regulatory T cells in residual tumors after iRFA of HCC. Moreover, the smallest tumor volumes and the longest survival were observed in the triple combination treatment (iRFA+OK-432 +αPD-1 antibody) group compared with the other four groups.
CONCLUSIONS
The combined therapy of OK-432 with αPD-1 antibody induced a strong antitumor immune response, which significantly inhibited the residual tumors after iRFA of HCC. This concept may provide a new treatment strategy to increase the curative efficacy of RFA for medium-to-large and irregular HCCs.
AVAILABILITY OF DATA AND MATERIAL
The data of this study are available from the corresponding author on reasonable request.
Topics: Mice; Animals; Carcinoma, Hepatocellular; Neoplasm, Residual; Picibanil; CD8-Positive T-Lymphocytes; Liver Neoplasms; Mice, Inbred Strains; Antibodies; Radiofrequency Ablation
PubMed: 37625323
DOI: 10.1016/j.biopha.2023.115351 -
Internal Medicine (Tokyo, Japan) 2017Objective Pleurodesis is an effective therapy for malignant pleural effusion (MPE). While interstitial lung disease (ILD) has been regarded as a serious complication of...
Objective Pleurodesis is an effective therapy for malignant pleural effusion (MPE). While interstitial lung disease (ILD) has been regarded as a serious complication of pleurodesis, its clinicopathological characteristics have not been fully understood. This study was conducted to elucidate the incidence of ILD and the risk factors for ILD in patients who underwent pleurodesis to control MPE. Methods The medical records of patients who underwent pleurodesis in Aichi Medical University between March 2008 and February 2013, the period before the approval of talc in Japan, were retrospectively analyzed. Results A total of 84 patients underwent pleurodesis, all using OK-432. ILD occurred in 13 patients (15.5%). The development of ILD after pleurodesis was significantly associated with old age (odds ratio [OR]: 4.82, 95% confidence interval [CI]: 1.22-19.08) and epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) treatment (OR: 5.97, CI: 1.7-20.9). A multivariate analysis revealed that >67 years of age (p=0.01) and EGFR-TKI treatment (p=0.02) were significantly associated with the development of pleurodesis-related ILD. Among the patients who received both pleurodesis and EGFR-TKIs (n=23), 8 patients developed ILD. All of these patients were receiving EGFR-TKI therapy at the time of pleurodesis or within 30 days after pleurodesis. In contrast, no cases of ILD were observed among the patients who stopped EGFR-TKIs before pleurodesis or started EGFR-TKIs at more than 30 days after pleurodesis. Conclusion ILD seemed to be a frequent complication of pleurodesis in patients using OK-432, especially elderly patients and those who underwent pleurodesis while receiving EGFR-TKI therapy or who started EGFR-TKI therapy within 30 days after pleurodesis.
Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Female; Humans; Japan; Lung Diseases, Interstitial; Male; Middle Aged; Odds Ratio; Picibanil; Pleural Effusion, Malignant; Pleurodesis; Retrospective Studies; Risk Factors
PubMed: 28717073
DOI: 10.2169/internalmedicine.56.7464 -
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 -
The Medical Journal of Malaysia Dec 2016Lymphangiomas are congenital malformations of the lymphatic system with characteristic dilated endothelium-lined spaces. It is vulnerability to infection or chemical...
BACKGROUND
Lymphangiomas are congenital malformations of the lymphatic system with characteristic dilated endothelium-lined spaces. It is vulnerability to infection or chemical irritants cause spontaneous reduction in size and in some cases complete resolution. Intralesional injection of OK-432 or Picibanil (lyophilized incubation mixture of Group A Streptococcus pyogenes of human origin) is slowly gaining recognition as its safety and efficacy standards have shown to avoid complications resulting from surgical interventions. The objective of this study was to evaluate the clinical outcomes of cystic hygroma patients who received OK-432 injections.
METHODS
In between 2011 and 2013, six patients with cystic hygroma received intralesional injection of OK-432. All the patients were assessed clinically and radiologically either via ultrasound, computer tomography (CT) or magnetic resonant imaging (MRI) prior to and after receiving the injections. Patients' response towards treatment was classified as total shrinkage, marked shrinkage (greater than 50% reduction in size), slight shrinkage (less than 50% reduction in size) or non-responsive to treatment.
RESULTS
Mean duration of follow-up was 12 months. Total shrinkage was achieved in one patient, marked shrinkage in three patients and one patient experienced mild shrinkage. Only one out of the six patients showed no response to treatment. None of the patients in this study experienced serious complications or adverse effects post intralesional injection of OK-432.
CONCLUSIONS
Intralesional OK-432 injection is an effective and safe alternative in treating cystic hygroma.
Topics: Antineoplastic Agents; Humans; Injections, Intralesional; Lymphangioma; Lymphangioma, Cystic; Picibanil; Tomography, X-Ray Computed
PubMed: 28087956
DOI: No ID Found -
Biomedicine & Pharmacotherapy =... May 2019The occurrence of seroma formation and long-term wound healing remain challenging complications after modified radical mastectomy. Sapylin is a drug used to reduce... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The occurrence of seroma formation and long-term wound healing remain challenging complications after modified radical mastectomy. Sapylin is a drug used to reduce seroma formation and enhance wound closure, but these results remain controversial. We aimed to investigate the potential mechanism.
METHODS
A prospective, consecutive cohort study included 120 patients diagnosed with breast cancer who underwent modified radical mastectomy was designed. Patients were randomized into two group, using or not using OK-432 (sixty patients per group) during surgeries. Patients' drainage fluids were collected for three days after surgery. Inflammatory cytokines and chemokines were measured with ELISA assays. The proliferative, migratory, and angiogenic capacity of HUVEC and HFL1 cells HUVEC and HFL1 cells were measured after being treated with drainage fluids.
RESULTS
Our clinic data showed that there was no statistical significance between the two groups in patient characteristics before surgery. However, the outcomes of patients in experimental group were significantly better than those in control group. In vitro studies, the results of ELISA assays showed that several cytokines, including IL-1a, IL-6, TGF-β1, bFGF and VEGF were increased in the drainage fluids treated with Sapylin. The proliferative, migratory, and angiogenic capacity of HUVEC and HFL1 cells were significantly enhanced after being treated with Sapylin group drainage fluids.
CONCLUSION
Sapylin could stimulate the body to secrete a variety of cytokines to promote wound healing by promoting endothelial cell proliferation and migration, angiogenesis and by increasing fibroblast migration and collagen deposition.
Topics: Breast Neoplasms; Cell Movement; Cell Proliferation; Cohort Studies; Collagen; Cytokines; Female; Human Umbilical Vein Endothelial Cells; Humans; Inflammation; Mastectomy; Middle Aged; Neovascularization, Physiologic; Picibanil; Postoperative Complications; Prospective Studies; Seroma; Surgical Wound; Wound Healing
PubMed: 30844656
DOI: 10.1016/j.biopha.2019.108706 -
International Journal of Molecular... Jul 2022Dendritic cells (DC) and leukaemia derived DC (DC) are potent stimulators of anti-leukaemic activity in acute myeloid leukaemia (AML) and can be generated from...
Dendritic cells (DC) and leukaemia derived DC (DC) are potent stimulators of anti-leukaemic activity in acute myeloid leukaemia (AML) and can be generated from mononuclear cells in vitro following standard DC/DC-generating protocols. With respect to future clinical applications though, DC/DC-generating protocols specifically designed for application in a whole-blood-(WB)-environment must be established. Therefore, we developed ten new DC/DC-generating protocols (kits; Kit-A/-C/-D/-E/-F/-G/-H/-I/-K/-M) for the generation of DC/DC from leukaemic WB, containing calcium-ionophore, granulocyte-macrophage-colony-stimulating-factor (GM-CSF), tumour-necrosis-factor-alpha, prostaglandin-E (PGE), prostaglandin-E (PGE) and/or picibanil (OK-432). All protocols were evaluated regarding their performance in generating DC/DC using refined classification and/or ranking systems; DC/DC were evaluated regarding their performance in stimulating anti-leukaemic activity using a cytotoxicity fluorolysis assay. Overall, we found the new kits capable to generate (mature) DC/DC from leukaemic WB. Through refined classification and ranking systems, we were able to select Kit-I (GM-CSF + OK-432), -K (GM-CSF + PGE) and -M (GM-CSF + PGE) as the most efficient kits in generating (mature) DC/DC, which are further competent to stimulate immunoreactive cells to show an improved anti-leukaemic cytotoxicity as well. This great performance of Kit-I, -K and -M in mediating DC/DC-based anti-leukaemic immunity in a WB-environment in vitro constitutes an important and directive step for translating DC/DC-based immunotherapy of AML into clinical application.
Topics: Dendritic Cells; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Leukemia, Myeloid, Acute; Picibanil; Prostaglandins; Prostaglandins E
PubMed: 35955486
DOI: 10.3390/ijms23158333 -
Cureus Sep 2022Orbital and periorbital venolymphatic malformations (VLMs) are benign congenital vascular lesions and constitute 1%-3% of all orbital masses. Widespread facial venous...
Orbital and periorbital venolymphatic malformations (VLMs) are benign congenital vascular lesions and constitute 1%-3% of all orbital masses. Widespread facial venous malformations have a high incidence of associated intracranial developmental venous anomalies (DVAs). In such cases, there can be a sudden increase in proptosis following upper respiratory infection or minor trauma. Numerous percutaneous intralesional sclerosing agents like sodium tetradecyl sulfate (STS), bleomycin, doxycycline, ethanol, and OK-432 (Picibanil) have been used for treating VLMs. We hereby report a rare case of retro-orbital VLM treated successfully with STS injection and an isolated dural arterio-venous (AV) fistula in the same patient.
PubMed: 36259024
DOI: 10.7759/cureus.29173 -
International Journal of Molecular... Sep 2019Dendritic cells (DCs) and leukemia-derived DC (DC) are potent stimulators of various immunoreactive cells and they play a pivotal role in the (re-) activation of the...
Dendritic cells (DCs) and leukemia-derived DC (DC) are potent stimulators of various immunoreactive cells and they play a pivotal role in the (re-) activation of the immune system. As a potential treatment tool for patients with acute myeloid leukemia, we developed and analyzed two new PGE-containing protocols (Pici-, Kit M) to generate DC/DC ex vivo from leukemic peripheral blood mononuclear cells (PBMCs) or directly from leukemic whole blood (WB) to simulate physiological conditions. Pici- generated significantly higher amounts of DCs from leukemic and healthy PBMCs when compared to control and comparable amounts as the already established protocol Pici-. The proportions of sufficient DC-generation were even higher after DC/DC-generation with Pici-. With Kits, it was possible to generate DCs and DC directly from leukemic and healthy WB without induction of blast proliferation. The average amounts of generated DCs and DC-subgroups were comparable with all Kits. The PGE containing Kit M generated significantly higher amounts of mature DCs when compared to the PGE-containing Kit K and increased the anti-leukemic-activity. In summary PGE-containing protocols were suitable for generating DC/DC from PBMCs as well as from WB, which reliably (re-) activated immunoreactive cells, improved the overall ex vivo anti-leukemic activity, and influenced cytokine-release-profiles.
Topics: Adult; Aged; Alprostadil; Biomarkers; Cell Differentiation; Cytokines; Dendritic Cells; Female; Flow Cytometry; Humans; Immunomodulation; Immunophenotyping; Leukemia, Myeloid, Acute; Leukocytes, Mononuclear; Male; Middle Aged; Picibanil; Young Adult
PubMed: 31533251
DOI: 10.3390/ijms20184590 -
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 -
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