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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 -
Otology & Neurotology : Official... Sep 2019The aim of this article was to investigate the effectiveness and underlying mechanisms of OK-432 therapy in patients with auricular hematomas.
OBJECTIVES
The aim of this article was to investigate the effectiveness and underlying mechanisms of OK-432 therapy in patients with auricular hematomas.
STUDY DESIGN AND SETTING
Case series with planned data collection.
SUBJECTS AND METHODS
We tried this therapy in 47 patients with auricular hematoma between April 2008 and August 2018. We aspirated as much of the fluid content of each lesion as possible with a 21-gage needle. We injected OK-432 solution into the lesion with the same needle that we used for aspiration. We performed this treatment at an outpatient basis without hospitalization.
RESULTS
Disappearance and marked reduction of the lesion were observed in all patients who had this therapy, and local scarring and deformity of the auricle did not occur in any patients. As adverse effects, local pain at the injection site and fever (37-38.5°C) were observed in some cases of the patients who had this therapy. The concentrations of various cytokines in each aspirate before and after OK-432 therapy were investigated. The production of tumor necrosis factor-α, interleukin-6, interleukin-8, interferon gamma, vascular endothelial growth factor, and periostin was significantly elevated in the aspirate fluid after OK-432 therapy.
CONCLUSION
OK-432 therapy is simple, easy, safe, effective, and can be used as a substitute for surgery in the treatment of auricular hematoma.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Ear Auricle; Ear Diseases; Female; Hematoma; Humans; Male; Middle Aged; Paracentesis; Picibanil; Retrospective Studies; Treatment Outcome; Young Adult
PubMed: 31348135
DOI: 10.1097/MAO.0000000000002336 -
Otolaryngologia Polska = the Polish... Jun 2021<b>Introduction:</b> Recurrent thyroglossal duct cyst after surgery is not a rare condition and first-line treatment has not been established...
<b>Introduction:</b> Recurrent thyroglossal duct cyst after surgery is not a rare condition and first-line treatment has not been established yet.<br/><br/> <b>Aim:</b> Evaluation of outcomes and complications of OK-432 treatment in patients with recurrent thyroglossal duct cyst after surgery. <br/><br/> <b>Material and methods:</b> This study is designed as a case series with planned data collection at Tohoku Medical and Pharmaceutical University and Fukase Clinic. Five patients with recurrent thyroglossal duct cyst after surgery received this therapy between January 2014 and February 2020 on an outpatient basis, without hospitalization. OK-432 solution was injected into the lesion using an 18- or 27-gauge needle, depending on the location and size of the lesion, as well as on possible complications.<br/> <br/> <b>Results:</b> Lesions showed marked reduction or total shrinkage in all patients, with no local scarring or deformity at the injection site. Side effects manifested as local pain at the site of injection and fever (37.5-38.5°C) observed in three patients, but the symptoms resolved within a few days.<br/> <br/> <b>Conclusions:</b> Since OK-432 therapy is simple, easy, safe and effective, it can be used as an alternative to surgery in the treatment of recurrent thyroglossal duct cyst after surgery.
Topics: Child; Humans; Picibanil; Thyroglossal Cyst
PubMed: 35175217
DOI: 10.5604/01.3001.0014.9073 -
Clinical Immunology (Orlando, Fla.) Sep 2022(Leukaemia derived) dendritic cells (DC, DC) are potent stimulators of anti-leukaemic activity in acute myeloid leukaemia (AML) and can be generated with...
Immunomodulatory kits generating leukaemia derived dendritic cells do not induce blast proliferation ex vivo: IPO-38 as a novel marker to quantify proliferating blasts in acute myeloid leukaemia.
(Leukaemia derived) dendritic cells (DC, DC) are potent stimulators of anti-leukaemic activity in acute myeloid leukaemia (AML) and can be generated with immunomodulatory kits containing granulocyte-macrophage-colony-stimulating-factor (GM-CSF), prostaglandin-E (PGE), prostaglandin-E (PGE) and/or picibanil (OK-321). Potential adverse effects initiated through kits, especially the proliferation of blasts, must be ruled out to ensure treatment safety. We quantified proliferating blasts with the proliferation markers CD71 and Ki-67 and the novel proliferation marker IPO-38 before and after kit treatment ex vivo. IPO-38 hereby appeared to be the most sensitive marker; a combination with CD71 may add value when assessing proliferation kinetics. Kit treatment did not or only slightly (<5%) induce blast proliferation in most cases. An induction of blast proliferation was only found in single cases and could be compensated by DC-induced anti-leukaemic activity in most times. Overall, we appraise kit treatment to be safe in vivo.
Topics: Biomarkers; Cell Proliferation; Dendritic Cells; Humans; Leukemia, Myeloid, Acute; Prostaglandins; Prostaglandins E
PubMed: 35908638
DOI: 10.1016/j.clim.2022.109083 -
Journal of Pediatric Surgery May 2022Sclerotherapy is frequently employed in treating lymphatic malformations (LMs), and multiple agents, practitioners and strategies exist. This review investigates the...
PURPOSE
Sclerotherapy is frequently employed in treating lymphatic malformations (LMs), and multiple agents, practitioners and strategies exist. This review investigates the reported efficacy and safety of sclerosants in the pediatric population.
METHODS
Adhering to PRISMA guidelines, multiple databases were queried without linguistic or temporal restriction. Inclusion criteria were patients aged 0-18 exclusively receiving injection sclerotherapy for the treatment of LMs with follow-up data. Data abstracted included agent, dose, anatomic site and key outcome measures including complications (major/minor) and resolution rates (>95% reduction in volume). Critical appraisal was undertaken using the MINORS tool.
RESULTS
Forty-eight studies met the inclusion criteria with a mean MINORS score of 0.65 ± 0.08. Included studies yielded 886 patients, across nearly 30 years. The overall observed rate of success was 89%, with variable follow-up across publications (6 weeks - 10 years). Most reported LMs were macrocystic (82%) and had a higher resolution rate than mixed/microcytic variants (89%, 71%, 34%, p<0.01) For head/neck LMs, rates of complete regression for OK-432, bleomycin, and doxycycline were 67% ± 27% (n = 26), 91% ± 53% (n = 34) and 85% ± 16% (n = 52) respectively. Major complications were most commonly reported with OK-432, including airway compromise or subsequent operation.
CONCLUSIONS
In pediatric patients treated for LM by sclerotherapy, complication rates were low. Macrocystic lesions respond well but success rates were modest at best for microcystic disease. Differences in agent utilization were noted between high and low resourced contexts; despite its lack of federal approval, OK-432 was the most reported agent. Further prospective research is warranted. LOE: 3a.
Topics: Child; Humans; Infant; Lymphatic Abnormalities; Neck; Picibanil; Retrospective Studies; Sclerosing Solutions; Sclerotherapy; Treatment Outcome
PubMed: 35151497
DOI: 10.1016/j.jpedsurg.2021.12.056 -
Annals of Nuclear Medicine Oct 2020This study aimed to determine changes in FDG-PET/CT after pleurodesis with OK-432 and to investigate differences in the changes between non-malignant and malignant...
OBJECTIVE
This study aimed to determine changes in FDG-PET/CT after pleurodesis with OK-432 and to investigate differences in the changes between non-malignant and malignant lesions.
METHODS
Study participants were 17 patients with a history of malignant chest disease who underwent FDG-PET/CT after pleurodesis using OK-432 and in whom pleural lesions were determined to be non-malignant (n = 8) or malignant (n = 9). FDG uptake (SUV) was counted on all pleural lesions. CT findings (CT attenuation, shape) of pleural lesions with increased FDG uptake were evaluated.
RESULTS
The number of patients with increased FDG uptake in the pleura differed significantly between the non-malignant group (3/8) and malignant group (9/9) (p < 0.01) The mean SUV of non-malignant lesions with increased FDG uptake was 2.3 ± 0.7 vs. 6.2 ± 2.2 in malignant lesions, for a significant difference (p < 0.01). The mean CT attenuation of lesions was 36 ± 11 HU in the non-malignant group and 34 ± 14 HU in the malignant group, a difference that was not significant (p = 0.91). There was a significant difference in nodular and linear shapes between non-malignant and malignant lesions (p < 0.01). All non-malignant lesions were linear.
CONCLUSIONS
Positive FDG uptake was shown in non-malignant pleural lesions as well as in malignant pleural lesions after pleurodesis using OK-432. Combined analysis of FDG accumulation and CT morphology is helpful to distinguish between benign and malignant lesions.
Topics: Adult; Aged; Biological Transport; Female; Fluorodeoxyglucose F18; Humans; Male; Middle Aged; Picibanil; Pleura; Pleurodesis; Positron Emission Tomography Computed Tomography
PubMed: 32809160
DOI: 10.1007/s12149-020-01508-0 -
Oral and Maxillofacial Surgery Mar 2020Lymphangiomas are relatively uncommon head and neck region lymphatic malformations. Although surgery can be still considered the mainstay of treatment, sclerotherapy by...
INTRODUCTION
Lymphangiomas are relatively uncommon head and neck region lymphatic malformations. Although surgery can be still considered the mainstay of treatment, sclerotherapy by OK-432 is becoming a widespread treatment option. The aim of this article is to present and discuss the management and outcomes of a series of cases of lymphangiomas.
METHODS
All patients with lymphangiomas who were treated from 2010 to 2018 were reviewed. The following data were recorded: age, gender, subtype, staging, type of treatment, outcome, and recurrence.
RESULTS
Fifteen patients (9 females, 6 males) were included with 2 microcystic and 13 macrocystic lymphangiomas. Six patients underwent surgery with excision (5 with a complete success, one with a fair success), whereas the remaining 9 subjects underwent sclerotherapy by OK-432 (6 with a complete success, 3 with a fair success). No postoperative complications were observed.
CONCLUSIONS
All modes of treatment are important in properly selected patients affected by lymphangiomas. OK-432 therapy is a safe and effective option in the treatment of head and neck lymphangiomas.
Topics: Female; Humans; Infant; Lymphangioma; Lymphatic Abnormalities; Male; Neoplasm Recurrence, Local; Picibanil; Sclerotherapy; Treatment Outcome
PubMed: 31960163
DOI: 10.1007/s10006-020-00832-z -
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 -
Acta Oto-laryngologica May 2021Ranula is a rare benign cystic lesion in the floor of the mouth, which can herniate through the mylohyoid muscle and become a plunging ranula. Treatment for ranulas is... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Ranula is a rare benign cystic lesion in the floor of the mouth, which can herniate through the mylohyoid muscle and become a plunging ranula. Treatment for ranulas is currently surgical excision of the sublingual gland. Sclerotherapy with OK-432 is a well-established treatment of lymphatic malformations, but not yet thoroughly evaluated on ranulas. Objectives: To evaluate sclerotherapy of ranulas with OK-432 in a randomized double-blinded trial.
MATERIALS AND METHODS
20 patients with plunging or intraoral ranula were randomized to two double-blinded injections with OK-432 or saline. Effect on the ranula and evaluation of symptoms and QOL were investigated.
RESULTS
Treatment response differed significantly between OK-432 and placebo, = .041(student's T-test). All patients with intraoral ranulas had a complete response, but only 1/4 of the patients with plunging ranula. The inflammatory reaction after injection with OK-432 caused a mild to moderate impact on QOL. No serious complications were observed.
CONCLUSION
This study suggests that sclerotherapy with OK-432 in ranula is a very effective treatment for intraoral ranulas, but possibly less useful in plunging ranulas.
SIGNIFICANCE
This is a limited study, but we believe that sclerotherapy with OK-432 should be recommended as primary treatment at least for intraoral ranulas.
Topics: Adolescent; Adult; Antineoplastic Agents; Child; Double-Blind Method; Female; Humans; Injections, Intralesional; Male; Middle Aged; Picibanil; Prospective Studies; Ranula; Sclerotherapy; Young Adult
PubMed: 33775200
DOI: 10.1080/00016489.2021.1889660 -
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