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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 -
Acta Paediatrica (Oslo, Norway : 1992) Aug 2019We assessed the long-term health-related quality of life (HRQoL) of children who received sclerotherapy for lymphatic malformations. This treatment involved injecting...
Long-term health-related quality of life in children with lymphatic malformations treated with sclerotherapy generally matched age-appropriate standardised population norms.
AIM
We assessed the long-term health-related quality of life (HRQoL) of children who received sclerotherapy for lymphatic malformations. This treatment involved injecting drugs into the blood vessels to make them shrink.
METHODS
Our cross-sectional study retrospectively reviewed patients who received OK-432 sclerotherapy injections at Karolinska University Hospital, Stockholm, Sweden, from 1998 to 2013. We studied 49 patients (63% female) aged 8-18 at least five years after their first injection. HRQoL was assessed with the KIDSCREEN-52 questionnaire and a study-specific questionnaire addressed disease consequences and patient satisfaction. We determined associations between HRQoL and disease and treatment and the patient's sex.
RESULTS
Overall HRQoL paralleled age-appropriate norms in the general population, but some subgroups had lower levels. Regression-based estimates showed that larger numbers of injections were negatively associated with HRQoL in the dimensions autonomy, parent relations and home life, financial resources and school environment (p = 0.01-0.03). Malformations in the head and neck area were negative predictors across dimensions and were strongest for psychological well-being (p = 0.009), parent relations and home life (p = 0.017) and school environment (p = 0.006).
CONCLUSION
Despite generally positive outcomes, multiple injections and malformations in the head and neck were associated with impaired HRQoL.
Topics: Adolescent; Antineoplastic Agents; Child; Cross-Sectional Studies; Female; Humans; Lymphatic Abnormalities; Male; Picibanil; Quality of Life; Retrospective Studies; Sclerotherapy
PubMed: 30556934
DOI: 10.1111/apa.14700 -
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 -
Otolaryngology--head and Neck Surgery :... Dec 2021The role of sclerotherapy for vascular lesions of the head and neck is well established. However, the efficacy of sclerotherapy for benign cystic lesions of the head and... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The role of sclerotherapy for vascular lesions of the head and neck is well established. However, the efficacy of sclerotherapy for benign cystic lesions of the head and neck is less clear. The objective of this review is to determine the efficacy and safety of sclerotherapy for benign cystic lesions of the head and neck.
DATA SOURCES
PubMed/MEDLINE, Cochrane Library, and Embase.
REVIEW METHODS
The PRISMA guidelines (Preferred Reporting Systems for Systematic Reviews and Meta-analyses) were followed for this systematic review. Studies of patients with benign head and neck cystic masses treated primarily with sclerotherapy were included. Thirty-two studies met criteria for inclusion.
RESULTS
A total of 474 cases of sclerotherapy were reviewed. Agents comprised OK-432, ethanol, doxycycline, tetracycline, and bleomycin. Lesions in the analysis were ranula, thyroglossal duct cyst, branchial cleft cyst, benign lymphoepithelial cyst, parotid cyst, thoracic duct cyst, and unspecified lateral neck cyst. A total of 287 patients (60.5%) had a complete response; 132 (27.9%) had a partial response; and 55 (11.6%) had no response. OK-432 was the most widely utilized agent, with a higher rate of complete response than that of ethanol (62.0% vs 39.4%, = .015). Fifty-three cases (11.2%) required further surgical management. One case of laryngeal edema was reported and managed nonoperatively.
CONCLUSION
Sclerotherapy appears to be a safe and efficacious option for benign cystic lesions if malignancy is reliably excluded. Efficacy rates are comparable to those of sclerotherapy for vascular malformations. The rate of serious complications is low, with 1 incident of airway edema reported in the literature.
Topics: Branchioma; Cysts; Ethanol; Humans; Lymphocele; Neck; Parotid Diseases; Picibanil; Ranula; Sclerotherapy; Thyroglossal Cyst; Vascular Malformations
PubMed: 33755513
DOI: 10.1177/01945998211000448 -
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 -
Pediatric Surgery International Dec 2022Primary spontaneous pneumothorax (PSP) commonly occurs in lean, tall, male children and adolescents. To reduce recurrence rates of PSP, chemical pleurodesis could be... (Observational Study)
Observational Study
BACKGROUND
Primary spontaneous pneumothorax (PSP) commonly occurs in lean, tall, male children and adolescents. To reduce recurrence rates of PSP, chemical pleurodesis could be helpful for patients undergoing video-assisted thoracoscopic surgery (VATS) wedge bullectomy. The efficacy and safety of intraoperative OK-432 (Picibanil) pleurodesis on preventing the recurrence of PSP in pediatric patients remain unclear.
METHODS
It is a retrospective observational study in a single center, between 2014 and 2020, enrolled 48 (8 females) pediatric PSP patients with persistent air leakage at the mean age of 16.3 ± 1.1 years to receive VATS wedge bullectomy and pleural abrasion. Twenty patients received additional intraoperative OK-432 pleurodesis. The clinical characteristics of patients, surgical outcomes, and recurrence rates were analyzed.
RESULTS
The OK-432 group had longer operation time (118.6 ± 35.6 vs. 96.5 ± 23.3 min; p < 0.05) and higher proportion of postoperative fever (75.0% vs. 28.5%; p = 0.015) than the standard group. No serious adverse events were noted and other surgical outcomes in the two groups were comparable. After a mean follow-up period of 18.1 ± 19.1 months, the OK-432 group had a lower recurrence rate compared with the standard group (5% vs. 28.6%; p < 0.05, odds ratio 0.13, 95% confidence interval: 0.01-1.15), but it had no significant difference in statistics on the Kaplan-Meier curves (log-rank p = 0.105).
CONCLUSION
It was the first study that focused on the addition of intraoperative OK-432 pleurodesis for PSP with persistent air leakage in children and adolescents receiving VATS. It demonstrated the efficacy with a low recurrence rate and short-term safety as a single-center experience.
LEVEL OF EVIDENCE
Retrospective review, therapeutic study, Level III.
Topics: Female; Humans; Male; Adolescent; Child; Pleurodesis; Pneumothorax; Picibanil; Treatment Outcome; Recurrence; Thoracic Surgery, Video-Assisted; Retrospective Studies
PubMed: 36575307
DOI: 10.1007/s00383-022-05347-0 -
International Journal of Radiation... Sep 2020In this study, we hypothesized that systemic antitumor immunity might be enhanced by combining pulsed-wave ultrasound hyperthermia (pUSHT) with OK-432 and that the...
PURPOSE
In this study, we hypothesized that systemic antitumor immunity might be enhanced by combining pulsed-wave ultrasound hyperthermia (pUSHT) with OK-432 and that the induced antitumor immunity could confer protection against tumorigenesis. These hypotheses were tested in bilateral and rechallenged tumor models.
METHODS AND MATERIALS
Bilateral and rechallenged tumor models were applied in the studies. In the bilateral tumor model, BALB/c mice were inoculated in both flanks with CT26-luc tumor cells. The tumors in the right flank were treated with 4 courses of pUSHT with or without OK-432. In the rechallenged tumor model, tumor cells were implanted into the right flank. Once formed, the tumors were treated with pUSHT with OK-432, followed by surgical resection. New tumor cells were then implanted into the contralateral flank. The antitumor response was evaluated via infiltrated immune cells and the severity of necrosis/apoptosis in tumors.
RESULTS
In the bilateral tumor model, the tumor growth rate and growth activity of both treated (100% reduction) and untreated tumors (90.5% reduction) were significantly inhibited with the combination treatment compared with the sham control group, and the systemic antitumor effect was prolonged. The survival rate was significantly enhanced (sham control, 8 days; OK plus pUSHT, >20 days). IFNγ CD4 (treated tumor, 8.6-fold; untreated tumor, 4-fold), IFNγ CD8 (treated tumor, 6.7-fold; untreated tumor, 2.6-fold), and T cell and NK cell (treated tumor, 4-fold; untreated tumor, 2.5-fold) infiltration was increased in the combination group compared with the control group. In the rechallenged tumor model, new tumors failed to form with the combination treatment.
CONCLUSION
This experimental study combining pUSHT and OK-432 explored a new therapeutic strategy for controlling colon cancer metastasis. The results show that the combination treatment may produce an effective antitumor immune response.
Topics: Adjuvants, Immunologic; Animals; Cell Line, Tumor; Cell Proliferation; Combined Modality Therapy; Hyperthermia, Induced; Mice; Picibanil; Ultrasonic Waves
PubMed: 32339644
DOI: 10.1016/j.ijrobp.2020.04.021 -
Gan To Kagaku Ryoho. Cancer &... Feb 2023The patient was a 42-year-old woman. After 4 courses of capecitabine therapy for right chest wall recurrence of breast cancer, ER(+, 10-15%), PgR(-), HER2(-), she... (Review)
Review
The patient was a 42-year-old woman. After 4 courses of capecitabine therapy for right chest wall recurrence of breast cancer, ER(+, 10-15%), PgR(-), HER2(-), she underwent pleurodesis using OK-432 for increased right pleural effusion. On the 12th day after pleurodesis diffuse infiltrative shadows in the right lung, and frosted shadows in both lungs, were observed, and she was diagnosed with drug-induced lung injury. About 3 weeks after administration of prednisolone 1 mg/ kg a tendency for improvement in lung injury was observed, but the patient died of breast cancer progression. Drug- induced lung injury by pleurodesis carries the risk of delaying resumption of chemotherapy. We report this case with a review of the literature.
Topics: Female; Humans; Adult; Pleural Effusion, Malignant; Picibanil; Breast Neoplasms; Pleurodesis; Lung Injury; Pleural Effusion; Lung Diseases, Interstitial
PubMed: 36807167
DOI: No ID Found -
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