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Ultrasound in Obstetrics & Gynecology :... Dec 2005
Review
Topics: Chylothorax; Fetal Diseases; Humans; Hydrops Fetalis; Picibanil; Pleurodesis
PubMed: 16273598
DOI: 10.1002/uog.2634 -
Transfusion Medicine and Hemotherapy :... Feb 2022Myeloid leukaemic blasts can be converted into leukaemia-derived dendritic cells (DC), characterised by the simultaneous expression of dendritic- and...
Interferon Gamma Secretion of Adaptive and Innate Immune Cells as a Parameter to Describe Leukaemia-Derived Dendritic-Cell-Mediated Immune Responses in Acute Myeloid Leukaemia in vitro.
INTRODUCTION
Myeloid leukaemic blasts can be converted into leukaemia-derived dendritic cells (DC), characterised by the simultaneous expression of dendritic- and leukaemia-associated antigens, which have the competence to prime and enhance (leukaemia-specific) immune responses with the whole leukaemic antigen repertoire. To display and further specify dendritic cell (DC)- and DC-mediated immune responses, we analysed the interferon gamma (IFNy) secretion of innate and adaptive immune cells.
METHODS
DC/DC were generated from leukaemic whole blood (WB) with (blast)modulatory Kit-I (granulocyte-macrophage colony-stimulating factor [GM-CSF] + Picibanil [OK-432]) and Kit-M (GM-CSF + prostaglandin E1) and were used to stimulate T cell-enriched immunoreactive cells. Initiated anti-leukaemic cytotoxicity was investigated with a cytotoxicity fluorolysis assay. Initiated IFNy secretion of T, NK, CIK, and iNKT cells was investigated with a cytokine secretion assay (CSA). IFNy positivity was additionally evaluated with an intracellular cytokine assay (ICA). Recent activation of leukaemia-specific cells was verified through addition of leukaemia-associated antigens (LAA; WT-1 and Prame).
RESULTS
We found Kit-I and Kit-M competent to generate mature DC and DC from leukaemic WB without induction of blast proliferation. Stimulation of immunoreactive cells with DC/DC regularly resulted in an increased anti-leukaemic cytotoxicity and increased IFNy secretion of T, NK, and CIK cells, pointing to the significant role of DC/DC in leukaemia-specific alongside anti-leukaemic reactions. Interestingly, an addition of LAA did not further increase IFNy secretion, suggesting an efficient activation of leukaemia-specific cells. Here, both the CSA and ICA yielded comparable frequencies of IFNy-positive cells. Remarkably, the anti-leukaemic cytotoxicity positively correlated with the IFNy secretion in T, T, T, and NK cells.
CONCLUSION
Ultimately, the IFNy secretion of innate and adaptive immune cells appeared to be a suitable parameter to assess and monitor the efficacy of in vitro and potentially in vivo acute myeloid leukaemia immunotherapy. The CSA in this regard proved to be a convenient and reproducible technique to detect and phenotypically characterise IFNy-secreting cells. In respect to our studies on DC-based immunomodulation, we were able to display the potential of DC/DC to induce or improve leukaemia-specific and anti-leukaemic activity.
PubMed: 35221867
DOI: 10.1159/000516886 -
Dental Research Journal Dec 2012Picibanil (OK-432) is a lyophilized mixture of group A Streptococcus pyogenes with antineoplastic activity. Because of its capacity to produce a selective fibrosis of...
BACKGROUND
Picibanil (OK-432) is a lyophilized mixture of group A Streptococcus pyogenes with antineoplastic activity. Because of its capacity to produce a selective fibrosis of lymphangiomas (LMs), it has been approved by Japanese administration in 1995 for the treatment of LMs.
MATERIALS AND METHODS
We treated 15 children (age range: 6-60 months) affected by head and neck macrocystic LMs with intracystic injections (single dose of 0.2 mL) of Picibanil (1-3 injections).
RESULTS
Complete disappearance of the lesion was noticed in eight (53.33%) cases, a marked (>50%) reduction of LMs was found five (33.33%) cases, while a moderate (<50%) response was recorded in two (13.33%) cases. Picibanil side effects included fever, local inflammation, and transitory increase of blood platelets' concentration; a single case of anemia was resolved with concentrated red blood cells transfusion.
CONCLUSIONS
Intracystic injection of Picibanil is an effective and safe treatment for macrocystic LMs in pediatric patients and may represent the treatment of choice in such cases, especially where surgical excision is associated with the risk of functional/cosmetic side effects.
PubMed: 23814582
DOI: 10.4103/1735-3327.109752 -
Cancer Cell International Jun 2022Colorectal cancer (CRC) with pulmonary metastasis usually indicates a poor prognosis, whereas patients may benefit from adoptive cell therapy. Tumor-specific cytotoxic T...
BACKGROUND
Colorectal cancer (CRC) with pulmonary metastasis usually indicates a poor prognosis, whereas patients may benefit from adoptive cell therapy. Tumor-specific cytotoxic T lymphocytes (CTLs) have been reported as a promising treatment for CRC. However, the antitumor effect of CTLs remains limited partially due to insufficient production of effector cells via the activation by antigen-presenting dendritic cells (DCs).
METHOD
This study showed that a combination of CD40 mAb and Picibanil (OK-432) could significantly enhance the activation of CTLs by DCs, both in vitro and in vivo. Flow cytometry, colon cancer mouse model, and pathological staining were employed to demonstrate the specific functions.
RESULTS
This approach promoted the maturation of DCs, augmented the production of stimulatory cytokines, and suppressed the secretion of inhibitory cytokines. Additionally, it facilitated the killing efficiency of CTLs via stimulating their proliferation while restraining the number of Tregs, concomitantly with the positive regulation of corresponding cytokines. Furthermore, the combined unit could hurdle the expansion of tumor cells on metastatic lungs in the colon cancer mouse model.
CONCLUSION
Collectively, the combination of CD40-mAb and OK-432 facilitated the maturation of DCs and enhanced the cytotoxicity of T cells, promising therapeutic approach against CRC.
PubMed: 35715855
DOI: 10.1186/s12935-022-02630-x -
Brazilian Journal of Otorhinolaryngology 2023This study aims to perform a meta-analysis to figure out the efficacy of OK-432 sclerotherapy between Macrocystic (MAC) lymphangiomas and Microcystic (MIC) lymphangiomas. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
This study aims to perform a meta-analysis to figure out the efficacy of OK-432 sclerotherapy between Macrocystic (MAC) lymphangiomas and Microcystic (MIC) lymphangiomas.
METHODS
We conducted a systematic review and meta-analysis to clarify the relationship between OK-432 and lymphangiomas. PubMed and ISI Web of Science were searched from inception to May 2022. Joanna Briggs Institute (JBI) manual was used to evaluate the risk of bias. We calculated pooled Relative Risks (RR) and 95% Confidence Interval (95% CI) using random effects model to evaluate the relations between OK-432 and lymphangiomas.
RESULTS
A total of 11 studies (including 352 cases) about OK-432 sclerotherapy for lymphangioma were included in the current meta-analyses. The results suggested that the efficacy of OK-432 was significantly in MAC lesions than in MIC (RR=1.51, 95% CI 1.298-1.764), with significant moderate degrees of heterogeneity among 11 studies (I=51.2%, p=0.025). Subgroup analyses suggested that there was significant association in both retrospective studies (RR=1.26, 95% CI 1.03-1.53) and classification (by 1 cm) (RR=1.37, 95% CI 1.04-1.80) were associated with the efficacy of OK-432.
CONCLUSION
To our knowledge, our study represents the first meta-analysis examining the efficacy of OK-432 in the treatment of different types of LMs. However, the regional differences and the age differences of the subjects are the main limitations of this study and should be avoided in further research. Our results suggested that OK-432 sclerotherapy for macrocystic lymphangiomas was more effective.
Topics: Humans; Picibanil; Sclerotherapy; Retrospective Studies; Lymphangioma; Cysts; Treatment Outcome
PubMed: 37331237
DOI: 10.1016/j.bjorl.2023.03.007 -
The Tohoku Journal of Experimental... Jan 2014Chylothorax results from various causes, such as malignancy, trauma, or infection. POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy,...
Chylothorax results from various causes, such as malignancy, trauma, or infection. POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) is a multisystemic syndrome that is associated with plasma cell disorder. Pleural effusion is a common manifestation of POEMS syndrome, but the association of POEMS syndrome with chylothorax has not been reported. We report on a 61-year-old female patient who initially presented with dyspnea and bilateral leg edema. Importantly, the patient had normal renal function. Her chest X-ray and computed tomographic imaging showed bilateral pleural effusion, and her chest drainage revealed chylothorax. Detailed examination failed to reveal the definitive cause of the chylothorax. She received several treatments for chylothorax, namely, a low-fat diet or fasting, total parenteral nutrition, a somatostatin analog (octreotide), thoracic duct ligation by video-assisted thoracic surgery, and pleurodesis. However, further examination revealed endocrinopathy, monoclonal plasma cell disorder, peripheral neuropathy, and elevation of the serum level of vascular endothelial growth factor. The patient's condition was consequently diagnosed as POEMS syndrome. Eventually, her chylothorax was controlled by pleurodesis, and she was transferred to another hospital for stem cell transplantation. Herein, we report on the apparent first case of POEMS syndrome with chylothorax. In some cases of idiopathic chylothorax, the underlying primary disease may be latent, such as in the present patient. POEMS syndrome is rare, but this syndrome should be included in the differential diagnosis of chylothorax with unexplained etiology.
Topics: Chylothorax; Diagnosis, Differential; Dyspnea; Edema; Female; Humans; L-Lactate Dehydrogenase; Leg; Middle Aged; POEMS Syndrome; Picibanil; Pleural Effusion; Thoracic Surgery, Video-Assisted; Treatment Outcome; Triglycerides
PubMed: 24477187
DOI: 10.1620/tjem.232.43 -
European Archives of... Mar 2010The head and neck squamous cell carcinoma microenvironments contain many immune cells and their secretory products. Many of these cells belong to the mononuclear... (Review)
Review
The head and neck squamous cell carcinoma microenvironments contain many immune cells and their secretory products. Many of these cells belong to the mononuclear phagocyte system. The aim of this review is to study the interactions between mononuclear phagocytes and head and neck squamous cell carcinoma tissue. The role of inflammation in tumours and the cytokine interleukin-6 will be highlighted. Future therapy strategies in the treatment of head and neck cancer might be directed towards mononuclear phagocytes and their cytokine production.
Topics: Antineoplastic Agents; Carcinoma, Squamous Cell; Chemotherapy, Adjuvant; Combined Modality Therapy; Cytokines; Humans; Immunity, Innate; Inflammation Mediators; Interleukin-6; Lymphocyte Activation; Macrophages; Monocytes; Mononuclear Phagocyte System; Neoplasm Staging; Otorhinolaryngologic Neoplasms; Phagocytosis; Picibanil; Prognosis; Tumor Burden
PubMed: 19967383
DOI: 10.1007/s00405-009-1153-y -
Taiwanese Journal of Obstetrics &... Apr 2015To investigate the efficacy and toxicity of immunomodulatory therapy (IMT) alone or as an add-on to palliative/salvage chemotherapy in patients with refractory/recurrent...
OBJECTIVE
To investigate the efficacy and toxicity of immunomodulatory therapy (IMT) alone or as an add-on to palliative/salvage chemotherapy in patients with refractory/recurrent epithelial ovarian cancer (EOC).
MATERIALS AND METHODS
We retrospectively analyzed the efficacy and toxicity of IMT in 15 patients with refractory/recurrent EOC who had previously received multiple chemotherapy regimens.
RESULTS
The median age of the patients was 56 years (range, 41-75 years). Three patients were platinum-sensitive, two were platinum-resistant, and the remaining 10 patients were refractory to platinum-based front-line chemotherapy. IMT consisted of picibanil (OK-432) on Day 1, interleukin-2 and/or interferon-α on Day 2 administered by subcutaneous injection (every week or 2-weekly). Five patients never received metronomic oral cyclophosphamide. After IMT, three patients achieved partial remission (PR, lasting for 11 months, ≥ 12 months, and 16 months), and six patients had stable disease (SD). The disease stabilizing rate (PR+SD) was 60% (3/3 in platinum-sensitive and 6/12 in platinum-resistant/refractory patients). The absolute lymphocyte count (ALC) at 1 month after IMT was significantly higher in the PR+SD group (median 1242.0/μL) than in the progression group (median 325.0/μL) (p = 0.012). No ≥ Grade 3 toxicities were observed. The median post-IMT survival time was 12 months (range, 2-39 months).
CONCLUSION
IMT alone or add-on to palliative/salvage chemotherapy for refractory/recurrent EOC achieves a substantial disease stabilizing rate without severe toxicity, which might be a potential option in selected patients. The ALC 1 month after IMT could be an early indicator to disease stabilization.
Topics: Adult; Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Ovarian Epithelial; Drug Administration Schedule; Female; Humans; Immunomodulation; Injections, Subcutaneous; Interferon-alpha; Interleukin-2; Middle Aged; Neoplasm Recurrence, Local; Neoplasms, Glandular and Epithelial; Ovarian Neoplasms; Palliative Care; Picibanil; Retrospective Studies; Salvage Therapy; Survival Rate; Treatment Outcome
PubMed: 25951718
DOI: 10.1016/j.tjog.2014.04.027 -
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 -
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