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Cureus Apr 2024We present a case of lung adenocarcinoma with malignant pleural effusion. Nineteen days after pleurodesis using minocycline and OK-432 (picibanil), pembrolizumab...
We present a case of lung adenocarcinoma with malignant pleural effusion. Nineteen days after pleurodesis using minocycline and OK-432 (picibanil), pembrolizumab monotherapy was initiated. Four days later, the patient experienced a persistent cough. Chest computed tomography showed that ground-glass opacity appeared on the same side as pleurodesis and spread bilaterally thereafter, which was diagnostic of immune checkpoint inhibitors (ICI)-related pneumonitis. As he presented a severe respiratory failure, corticosteroid therapy was administered. Two weeks later, respiratory failure completely resolved and the abnormal shadows dramatically improved. Our results indicate that severe ICI-related pneumonitis can develop within a short period after pleurodesis.
PubMed: 38784310
DOI: 10.7759/cureus.58798 -
Scientific Reports Feb 2017Active human dendritic cells (DCs), which efficiently induce immune responses through their functions as antigen-presenting cells, exhibit direct anti-tumour killing...
Active human dendritic cells (DCs), which efficiently induce immune responses through their functions as antigen-presenting cells, exhibit direct anti-tumour killing activity in response to some pathogens and cytokines. These antigen-presenting and tumour killing abilities may provide a breakthrough in cancer immunotherapy. However, the mechanisms underlying this killer DC activity have not been fully proven, despite the establishment of interferon-α (IFN-α)-generated killer DCs (IFN-DCs). Here mature IFN-DCs (mIFN-DCs), generated from IFN-DCs primed with OK-432 (streptococcal preparation), exhibited elevated expression of CD86 and human leukocyte antigen-DR (minimum criteria for DC vaccine clinical trials) as well as antigen-presenting abilities comparable with those of mature IL-4-DCs (mIL-4-DCs). Interestingly, the killing activity of mIFN-DCs, which correlated with the expression of CD56 (natural killer cell marker) and was activated via the tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) and Fas ligand pathway, was stronger than that of IFN-DCs and remarkably stronger than that of mIL-4-DCs. Therefore, mIFN-DCs exhibit great potential as an anti-cancer vaccine that would promote both acquired immunity and direct tumour killing.
Topics: Antigen Presentation; B7-2 Antigen; CD56 Antigen; Cancer Vaccines; Cell Differentiation; Cytotoxicity, Immunologic; Dendritic Cells; Dinoprostone; Fas Ligand Protein; Gene Expression Regulation; Granulocyte-Macrophage Colony-Stimulating Factor; HLA-DR Antigens; Humans; Immunophenotyping; Interferon-alpha; Interleukin-4; Monocytes; Picibanil; Primary Cell Culture; Signal Transduction; TNF-Related Apoptosis-Inducing Ligand
PubMed: 28191816
DOI: 10.1038/srep42145 -
Cancer May 2017There are limited options for the curative treatment of refractory bone and soft tissue sarcomas. The purpose of this phase 1/2 study was to assess the immunological and...
BACKGROUND
There are limited options for the curative treatment of refractory bone and soft tissue sarcomas. The purpose of this phase 1/2 study was to assess the immunological and clinical effects of dendritic cells (DCs) pulsed with autologous tumor lysate (TL) in patients with advanced bone and soft tissue sarcomas.
METHODS
Thirty-seven patients with metastatic or recurrent sarcomas were enrolled in this study. Peripheral blood mononuclear cells obtained from the patients were suspended in media containing interleukin 4 (IL-4) and granulocyte-macrophage colony-stimulating factor. Subsequently, these cells were treated with TL, tumor necrosis factor α, and OK-432. The DCs were injected into the inguinal or axillary region. One treatment course comprised 6 weekly DC injections. The toxicity, clinical response (tumor volume, serum interferon-γ [IFN-γ], and serum IL-12), and oncological outcomes were observed.
RESULTS
In total, 47 courses of DC therapy were performed in 37 patients. No severe adverse events or deaths associated with the DC injections were observed in the study patients. Increased serum IFN-γ and IL-12 levels were observed 1 month after the DC injection. Among the 37 patients, 35 patients were assessed for clinical responses: 28 patients showed tumor progression, 6 patients had stable disease, and 1 patient showed a partial response 8 weeks after the DC injection. The 3-year overall and progression-free survival rates of the patients were 42.3% and 2.9%, respectively.
CONCLUSIONS
Although DC therapy appears safe and resulted in an immunological response in patients with refractory sarcoma, it resulted in an improvement of the clinical outcome in only a small number of patients. Cancer 2017;123:1576-1584. © 2017 American Cancer Society.
Topics: Adolescent; Adult; Aged; Antineoplastic Agents; Bone Neoplasms; Child; Chondrosarcoma; Dendritic Cells; Disease-Free Survival; Female; Granulocyte-Macrophage Colony-Stimulating Factor; Histiocytoma, Malignant Fibrous; Humans; Immunotherapy; Interferon-gamma; Interleukin-12; Interleukin-4; Leiomyosarcoma; Leukocytes, Mononuclear; Male; Middle Aged; Osteosarcoma; Picibanil; Sarcoma; Sarcoma, Clear Cell; Sarcoma, Synovial; Soft Tissue Neoplasms; Treatment Outcome; Tumor Necrosis Factor-alpha; Young Adult
PubMed: 28241093
DOI: 10.1002/cncr.30606 -
International Journal of Molecular... Dec 2022Integrin beta 7 (β7), a subunit of the integrin receptor, is expressed on the surface of immune cells and mediates cell-cell adhesions and interactions, e.g., antitumor...
Integrin beta 7 (β7), a subunit of the integrin receptor, is expressed on the surface of immune cells and mediates cell-cell adhesions and interactions, e.g., antitumor or autoimmune reactions. Here, we analyzed, whether the stimulation of immune cells by dendritic cells (of leukemic derivation in AML patients or of monocyte derivation in healthy donors) leads to increased/leukemia-specific β7 expression in immune cells after T-cell-enriched mixed lymphocyte culture-finally leading to improved antileukemic cytotoxicity. Healthy, as well as AML and MDS patients' whole blood (WB) was treated with Kit-M (granulocyte-macrophage colony-stimulating factor (GM-CSF) + prostaglandin E1 (PGE1)) or Kit-I (GM-CSF + Picibanil) in order to generate DCs (DC or monocyte-derived DC), which were then used as stimulator cells in MLC. To quantify antigen/leukemia-specific/antileukemic functionality, a degranulation assay (DEG), an intracellular cytokine assay (INTCYT) and a cytotoxicity fluorolysis assay (CTX) were used. (Leukemia-specific) cell subtypes were quantified via flow cytometry. The Kit treatment of WB (compared to the control) resulted in the generation of DC/DC, which induced increased activation of innate and adaptive cells after MLC. Kit-pretreated WB (vs. the control) led to significantly increased frequencies of β7-expressing T-cells, degranulating and intracellular cytokine-producing β7-expressing immune cells and, in patients' samples, increased blast lysis. Positive correlations were found between the Kit-M-mediated improvement of blast lysis (vs. the control) and frequencies of β7-expressing T-cells. Our findings indicate that DC-based immune therapies might be able to specifically activate the immune system against blasts going along with increased frequencies of (leukemia-specific) β7-expressing immune cells. Furthermore, β7 might qualify as a predictor for the efficiency and the success of AML and/or MDS therapies.
Topics: Humans; Granulocyte-Macrophage Colony-Stimulating Factor; Dendritic Cells; Leukemia, Myeloid, Acute; Lymphocyte Activation; Cytokines; Integrins
PubMed: 36613907
DOI: 10.3390/ijms24010463 -
Clinics (Sao Paulo, Brazil) Aug 2014Here, we describe our experience with different therapeutic modalities used to treat cystic lymphangiomas in children in our hospital, including single therapy with... (Comparative Study)
Comparative Study
OBJECTIVE
Here, we describe our experience with different therapeutic modalities used to treat cystic lymphangiomas in children in our hospital, including single therapy with OK-432, bleomycin and surgery, and a combination of the three modalities.
METHODS
We performed a retrospective, cross-sectional study including patients treated from 1998 to 2011. The effects on macrocystic lymphangiomas and adverse reactions were evaluated. Twenty-nine children with cystic lymphangiomas without any previous treatment were included. Under general anesthesia, patients given sclerosing agents underwent puncture of the lesion (guided by ultrasound when necessary) and complete aspiration of the intralesional liquid. The patients were evaluated with ultrasound and clinical examinations for a maximum follow-up time of 4 years.
RESULTS
The proportions of patients considered cured after the first therapeutic approach were 44% in the surgery group, 29% in the bleomycin group and 31% in the OK-432 group. These proportions were not significantly different. Sequential treatment increased the rates of curative results to 71%, 74% and 44%, respectively, after the final treatment, which in our case was approximately 1.5 applications per patient.
CONCLUSION
The results of this study indicate that most patients with cystic lymphangiomas do not show complete resolution after the initial therapy, regardless of whether the therapy is surgical or involves the use of sclerosing agents. To achieve complete resolution of the lesions, either multiple operations or a combination of surgery and sclerotherapy must be used and should be tailored to the characteristics of each patient.
Topics: Bleomycin; Brazil; Child, Preschool; Combined Modality Therapy; Cross-Sectional Studies; Female; Follow-Up Studies; Head and Neck Neoplasms; Humans; Infant; Injections, Intralesional; Lymphangioma, Cystic; Male; Picibanil; Punctures; Remission Induction; Retrospective Studies; Sclerosing Solutions; Treatment Outcome
PubMed: 25141107
DOI: 10.6061/clinics/2014(08)01 -
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 -
International Immunopharmacology Mar 2024Radiofrequency ablation (RFA) has been used as an alternative to surgical management of early-stage hepatocellular carcinoma (HCC). However, when large and irregular...
Radiofrequency ablation (RFA) has been used as an alternative to surgical management of early-stage hepatocellular carcinoma (HCC). However, when large and irregular HCCs are subjected to RFA, a safety margin is usually difficult to obtain, thus causing a sublethal radiofrequency hyperthermia (RFH) at the ablated tumor margin. This study investigated the feasibility of using RFH to enhance the effect of OK-432 on HCC, with the aim to generate a tumor-free margin during RFA of HCC. Our results showed OK-432 could activate the cGAS-STING pathway, and RFH could further enhance the activation. Meanwhile, RFH could induce a high expression of TLR4, and TLR4 might be an upstream molecular of the cGAS-STING pathway. The combined therapy of RFH with OK-432 resulted in a better tumor response, and a prolonged survival compared to the other three treatments. In conclusion, RFH in combination with OK-432 might reduce the residual and recurrent tumor after RFA of large and irregular HCCs, and serve as a new option for other solid malignancies treated by RFA.
Topics: Carcinoma, Hepatocellular; Hyperthermia, Induced; Liver Neoplasms; Neoplasm Recurrence, Local; Picibanil; Retrospective Studies; Toll-Like Receptor 4; Antineoplastic Agents; Animals; Mice; Cell Line, Tumor; Radiofrequency Ablation; Mice, Inbred C57BL; Nucleotidyltransferases; Membrane Proteins; Male
PubMed: 38442584
DOI: 10.1016/j.intimp.2024.111769 -
Journal of Translational Medicine Jan 2017Minimally invasive therapies, such as microwave ablation (MWA), are widely used for the treatment of solid tumors. Previous studies suggest that MWA is feasible for the...
BACKGROUND
Minimally invasive therapies, such as microwave ablation (MWA), are widely used for the treatment of solid tumors. Previous studies suggest that MWA is feasible for the treatment of small breast cancer, and thermal ablation may induce adaptive antitumor immunity. However, the induced immune responses are mostly weak, and the immunomodulation effects of MWA in breast cancer are unclear. Immunostimulant OK-432 can induce tumor-specific T-cell responses and may augment the immunity induced by MWA.
METHODS
We treated 4T1 breast cancer bearing BALB/c mice with MWA, OK-432, MWA plus OK-432, or left without treatment. Survival time was evaluated with the Kaplan-Meyer method comparing survival curves by log-rank test. On day 25 after ablation, surviving mice received tumor rechallenge, and the rechallenged tumor volumes were calculated every 5 days. Immunohistochemistry and flow cytometry were used to evaluate the T-cell immune responses in ablated tissues and spleens. The tumor-specific immunity was assessed by enzyme-linked immunospot assays. Besides, the cytokine patterns were identified from enzyme-linked immunosorbent assay.
RESULTS
Microwave ablation plus OK-432 resulted in longer survival than single treatment and protect most surviving mice from tumor rechallenge. Both local and systemic T-cell responses were induced by MWA and were further enhanced by subsequent administration of OK-432. Moreover, the combination of MWA and OK-432 induced stronger tumor-specific immune responses than MWA alone. In addition, OK-432 and MWA synergistically promoted the production of Th1-type but not Th2-type cytokines, and polarized T-cell responses to Th1-dominant state.
CONCLUSIONS
The T-cell immune responses were activated by MWA in breast cancer. Furthermore, the combination of MWA and OK-432 induced Th1-type response and elicited specific antitumor immunity.
Topics: Animals; Cell Line, Tumor; Cell Polarity; Combined Modality Therapy; Cytokines; Disease Models, Animal; Female; Kaplan-Meier Estimate; Mammary Neoplasms, Animal; Mice, Inbred BALB C; Microwaves; Picibanil; Survival Analysis; T-Lymphocytes, Cytotoxic; Th1 Cells
PubMed: 28137271
DOI: 10.1186/s12967-017-1124-9 -
Asian Pacific Journal of Cancer... 2015OK-432, a Streptococcus-derived anticancer immunotherapeutic agent, has been applied in clinic for many years and achieved great progress in various cancers. In the...
OK-432, a Streptococcus-derived anticancer immunotherapeutic agent, has been applied in clinic for many years and achieved great progress in various cancers. In the present study, we investigated its anticancer effect on bladder cancer through tumor associated macrophages (TAMs). MTS assay validated OK-432 could inhibit proliferation in both T24 and EJ bladder cell lines. OK-432 also induced apoptosis of bladder cancer cells in vitro. Consequently, we demonstrated that OK-432 could suppress the bladder cancer cells migration and invasion by altering the EMT-related factors. Furthermore, using SD rat model, we revealed that OK-432 inhibited tumor growth, suppressed PCNA expression and inhibited metastasis in vivo. Taken together, these findings strongly suggest that OK-432 inhibits cell proliferation and metastasis through inducing macrophages to secret cytokines in bladder cancer.
Topics: Animals; Antineoplastic Agents; Apoptosis; Blotting, Western; Cell Movement; Cell Proliferation; Female; Flow Cytometry; Fluorescent Antibody Technique; Humans; Immunoenzyme Techniques; Macrophages; Picibanil; Rats; Rats, Sprague-Dawley; Tumor Cells, Cultured; Urinary Bladder Neoplasms; Xenograft Model Antitumor Assays
PubMed: 26107200
DOI: 10.7314/apjcp.2015.16.11.4537 -
Surgical Case Reports Dec 2019Conventional lymphangiography cannot detect leakage sites of hepatic lymphatic vessels. Percutaneous transhepatic lymphangiography can be used to visualize leakage...
BACKGROUND
Conventional lymphangiography cannot detect leakage sites of hepatic lymphatic vessels. Percutaneous transhepatic lymphangiography can be used to visualize leakage sites, and once the leakage site has been confirmed, effective sclerotherapy can be performed.
CASE PRESENTATION
A rare case of intractable hepatic lymphorrhea due to injury of the hepatoduodenal ligament following pancreaticoduodenectomy is reported. Drainage of massive ascites from the drainage tube continued after surgery. Percutaneous transhepatic lymphangiography visualized the intrahepatic lymphatic vessels and the leakage site at the hepatic hilum. An 8-Fr drainage catheter was inserted adjacent to the leakage point under fluoroscopic computed tomography guidance. Repeated sclerotherapy using intraperitoneal administration of OK-432 (picibanil) through the catheter was performed, which exposed the leakage site, and control of the ascites was finally achieved.
CONCLUSIONS
To the best of our knowledge, this is the first successful case of detection of a leakage site using intrahepatic lymphangiography, followed by sclerotherapy using OK-432.
PubMed: 31872305
DOI: 10.1186/s40792-019-0761-z