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European Journal of Dermatology : EJD Aug 2018
Topics: Aged; Antineoplastic Agents; Fatal Outcome; Hemangiosarcoma; Hemothorax; Humans; Male; Paclitaxel; Picibanil; Pleural Neoplasms; Pleurodesis; Pneumothorax; Recurrence; Skin Neoplasms
PubMed: 30105988
DOI: 10.1684/ejd.2018.3318 -
Cancer Immunology, Immunotherapy : CII Oct 2018Numerous trials using dendritic cell (DC)-based vaccinations for the treatment of cancer are being carried out. However, an improvement of the quality of DC used is...
Numerous trials using dendritic cell (DC)-based vaccinations for the treatment of cancer are being carried out. However, an improvement of the quality of DC used is highly warranted. We here generated human monocyte-derived dendritic cells using a 3 day protocol and stimulated the cells using a combination of OK432 (Picibanil), TLR7/8 ligand CL097, and reduced amounts of prostaglandin (PG)E. We analyzed phenotype, migratory, and T-cell stimulatory capacity compared to a cytokine cocktail consisting of IL-1β, IL-6, TNF, and PGE. The OK432 cocktail stimulated cells had a similar mature phenotype with upregulated co-stimulatory molecules, HLA-DR and CCR7 as the cytokine cocktail-matured cells and a similar cytokine profile except increased amounts of IL-12p70. Chemotaxis towards CCL19 was reduced compared to the cytokine cocktail, but increased compared to OK432 alone. The T-cell stimulatory capacity was similar to the cytokine cocktail stimulated cells. In conclusion, the OK432 cocktail has the advantage of inducing IL-12p70 production without impairing phenotype or T-cell stimulatory capacity of the cells and might, therefore, be an advantageous alternative to be used in DC-based immunotherapy.
Topics: Antineoplastic Agents; Cell Differentiation; Cell Movement; Cells, Cultured; Cytokines; Dendritic Cells; Dinoprostone; Humans; Immunotherapy; Ligands; Monocytes; Neoplasms; Oxytocics; Picibanil; Toll-Like Receptor 7; Toll-Like Receptor 8
PubMed: 30069688
DOI: 10.1007/s00262-018-2216-y -
Journal of Chemotherapy (Florence,... Jul 2018Vinorelbine is a very potent chemotherapeutic agent which is used to treat a number of cancers including breast and non-small cell lung tumors. Vinorelbine mainly acts... (Review)
Review
Vinorelbine's anti-tumor actions may depend on the mitotic apoptosis, autophagy and inflammation: hypotheses with implications for chemo-immunotherapy of advanced cancers and pediatric gliomas.
Vinorelbine is a very potent chemotherapeutic agent which is used to treat a number of cancers including breast and non-small cell lung tumors. Vinorelbine mainly acts via blocking microtubules and induces a specific type of cell death called 'mitotic catastrophe/apoptosis' subsequent to mitotic slippage, which is the failure of cells to stay in a mitotic arrested state and replicating their DNA without cytokinesis. Glial tumor cells are especially sensitive to mitotic slippage. In recent years, vinorelbine demonstrated potency in pediatric optic and pontine gliomas. In this manuscript, we propose that vinorelbine's anti-tumor actions involve mitotic apoptosis, autophagy and inflammation. Intravenous infusion of vinorelbine induces a peculiar severe pain in the tumor site and patients with highly vascularized, oedematous and necrotic tumors are particularly vulnerable to this pain. Severe pain is a sign of robust inflammation and anti-inflammatory agents are used in treatment of this side effect. However, no one has questioned whether inflammation contributes to anti-tumor effects of vinorelbine, despite the existing data that vinorelbine induces Toll-Like Receptor-4 (TLR4), cytokines and cell death in endothelial cells especially under hypoxia. Robust inflammation may contribute to tumor necrosis such as seen during immunotherapy with lipopolysaccharides (LPS). Evidence also emerges that enhanced cyclooxygenase activity may increase cancer cell death in certain contexts. There are data indicating that non-steroidal anti-inflammatory drugs (NSAIDs) could block anti-tumor efficacy of taxanes, which also work mainly via anti-microtubule actions. Further, combining vinorelbine with immunostimulant cytokines provided encouraging results in far advanced melanoma and renal cell carcinoma, which are highly antigenic tumors. Vinorelbine also showed potential in treatment of inflammatory breast cancer. Finally, pontine gliomas - where partial activity of vinorelbine is shown by some studies - are also tumors which partially respond to immune stimulation. Animal experiments shall be conducted whether TLR4-activating molecules or immune-checkpoint inhibitors could augment anti-tumor actions of vinorelbine. Noteworthy, TLR4-activation seems as the most promising way of cancer immunotherapy, as a high percentage of molecules which demonstrated clinical benefits in cancer treatment are activators of TLR4, including BCG vaccine, monophosphoryl lipid A and picibanil (OKT-432). The provided data would be meaningful for the oncological practice.
Topics: Adjuvants, Immunologic; Antineoplastic Agents, Phytogenic; Apoptosis; Autophagy; Cytokines; Glioma; Humans; Inflammatory Breast Neoplasms; Toll-Like Receptor 4; Vinorelbine
PubMed: 30025492
DOI: 10.1080/1120009X.2018.1487149 -
Respiratory Investigation Sep 2018Pneumothorax occasionally develops in patients with interstitial pneumonia (IP) and is often intractable. As there exists no well-established treatment for pneumothorax...
BACKGROUND
Pneumothorax occasionally develops in patients with interstitial pneumonia (IP) and is often intractable. As there exists no well-established treatment for pneumothorax with IP, we evaluated the efficacy and safety of pleurodesis with OK-432, a lyophilized preparation of Streptococcus pyogenes Su strain that has been inactivated by benzylpenicillin.
METHODS
We retrospectively evaluated the efficacy and safety of pleurodesis using OK-432 in 39 patients treated for IP-related pneumothorax between January 2006 and May 2017. Five to 10 Klinische Einheit (KE) of OK-432 was injected through the chest tube of each patient. Pleurodesis was considered successful if 1) the chest tube was removed without air leaks and 2) there was no recurrence of pneumothorax within 4 weeks after tube removal, and no additional treatment was required.
RESULTS
OK-432 pleurodesis was performed 46 times in 39 patients. The median number of OK-432 intrapleural injections received was 1 (range, 1-6), and median dose was 10 KE (range, 5-55 KE). The success rate was 63% (29/46) and recurrence rate was 17.4% (8/46). Grade 5 adverse events were observed in eight patients, including two patients who developed acute exacerbation of IP. Patients in whom the first OK-432 pleurodesis was successful had a significantly longer median survival time than patients in whom it was unsuccessful (322 days vs. 70 days, p = 0.036).
CONCLUSIONS
Our results show that OK-432 pleurodesis is an effective treatment for pneumothorax associated with IP; however, clinicians should be aware of the possibility of adverse events, especially in patients who are critically ill.
Topics: Adult; Aged; Aged, 80 and over; Female; Humans; Lung Diseases, Interstitial; Male; Middle Aged; Picibanil; Pleurodesis; Pneumothorax; Retrospective Studies; Time Factors; Treatment Outcome; Young Adult
PubMed: 29903606
DOI: 10.1016/j.resinv.2018.05.003 -
Therapeutic Apheresis and Dialysis :... Jun 2018The prognosis of metastatic or relapsed renal cell carcinoma (RCC) or bladder cancer (BC) remains poor despite the introduction of immune checkpoint blockade agents. We... (Comparative Study)
Comparative Study
Vaccination of Urological Cancer Patients With WT1 Peptide-Pulsed Dendritic Cells in Combination With Molecular Targeted Therapy or Conventional Chemotherapy Induces Immunological and Clinical Responses.
The prognosis of metastatic or relapsed renal cell carcinoma (RCC) or bladder cancer (BC) remains poor despite the introduction of immune checkpoint blockade agents. We aimed to investigate the safety and the feasibility of a vaccination with WT1 peptide-loaded dendritic cells (DCs) and OK-432 adjuvant combined with molecular targeted therapy or conventional chemotherapy. Five eligible patients with metastatic or relapsed RCC and five eligible patients with BC were enrolled. No severe adverse events related to a vaccination were observed. Seven patients with RCC or non-muscle invasive BC had durable stable disease and three other patients had disease progression after DC vaccination. DC vaccination augmented WT1 specific immunity and the reduction of regulatory T cells which might be related to clinical outcome. These results indicate that DC-based immunotherapy combined with a molecular targeted therapy or a conventional chemotherapy is safe and feasible for patients in advanced stage of RCC or BC.
Topics: Aged; Aged, 80 and over; Antineoplastic Agents; Cancer Vaccines; Carcinoma, Renal Cell; Dendritic Cells; Disease Progression; Female; Humans; Kidney Neoplasms; Male; Middle Aged; Molecular Targeted Therapy; Neoplasm Metastasis; Neoplasm Recurrence, Local; Picibanil; Treatment Outcome; Urinary Bladder Neoplasms; WT1 Proteins
PubMed: 29851270
DOI: 10.1111/1744-9987.12694 -
Annals of Thoracic and Cardiovascular... Oct 2018Hydrothorax due to pleuroperitoneal communication (PPC) can occur in patients undergoing continuous ambulatory peritoneal dialysis (CAPD). We report our experiences of...
INTRODUCTION
Hydrothorax due to pleuroperitoneal communication (PPC) can occur in patients undergoing continuous ambulatory peritoneal dialysis (CAPD). We report our experiences of the safety and efficacy of the treatment of four patients with a novel video-assisted thoracoscopy method.
METHODS
Single-port video-assisted thoracoscopic surgery (VATS) was performed with a mini-thoracotomy of 5 cm in length. The PPC site was identified on the diaphragm and ligated using an endoscopic loop. The diaphragm was then covered using a polyglycolic acid (PGA) sheet, over which adhesive chemicals (OK432 and tetracycline) were sprayed.
RESULTS
We assessed the efficacy of our approach in four patients (one female and three males) aged 42-74 years (mean: 62.0 years). The hydrothoraxes were right sided in all the patients. The mean operation and postoperative drainage times were 92.5 min and 3.0 days, respectively. The hydrothoraxes did not recur in any patient during follow-up periods of 8-46 months.
CONCLUSION
Our suture- and staple-free technique is not only easy to perform but also appears to be safe and effective for the management of hydrothorax in patients receiving CAPD. Larger scale studies are now indicated.
Topics: Adult; Aged; Anti-Bacterial Agents; Drainage; Female; Humans; Hydrothorax; Ligation; Male; Middle Aged; Operative Time; Peritoneal Dialysis, Continuous Ambulatory; Picibanil; Polyglycolic Acid; Sutureless Surgical Procedures; Tetracycline; Thoracic Surgery, Video-Assisted; Thoracotomy; Treatment Outcome
PubMed: 29780074
DOI: 10.5761/atcs.nm.18-00066 -
Sultan Qaboos University Medical Journal Feb 2018Head and neck masses can present in different pathologies that usually vary according to the age of the patient. We report five cases of benign head or neck masses...
Head and neck masses can present in different pathologies that usually vary according to the age of the patient. We report five cases of benign head or neck masses occurring among patients of different ages who were managed at the Bahrain Defence Force Royal Medical Services Hospital, Ar-Rifaa, Bahrain, between 2005-2014. All of the patients were treated using the sclerotherapeutic agent OK-432. Although surgical removal is usually considered optimal treatment in the management of such cases, OK-432 appears to be a promising alternative.
Topics: Adult; Bahrain; Child, Preschool; Cysts; Female; Head; Head and Neck Neoplasms; Humans; Infant; Male; Middle Aged; Neck; Picibanil; Sclerotherapy
PubMed: 29666687
DOI: 10.18295/squmj.2018.18.01.014 -
Boletin Medico Del Hospital Infantil de... 2018Lymphatic vascular malformations (LVM) or formerly called lymphangiomas are congenital malformations present in about 1 out of 6000 to -16000 births. The most relevant...
BACKGROUND
Lymphatic vascular malformations (LVM) or formerly called lymphangiomas are congenital malformations present in about 1 out of 6000 to -16000 births. The most relevant classification system for lymphangioma management is based on the size of the cysts. Spontaneous resolution is uncommon; thus, expectant management is not recommended. The classic treatment is excisional surgery, but it can affect adjacent structures or have relapses, so, sclerosing substances like OK-432 are being studied. The majority of the studies are small in number of patients and are from Japan; the largest studies in Mexico are focused on specific lesions (macrocystic) or a determined anatomical region. To date, there are no studies of the population of the north of Mexico.
METHOD
The experience with OK-432 was described through a retrospective, descriptive study in patients with LVM, from 2011 to 2016, in a reference hospital of northern Mexico.
RESULTS
A total of 26 patients with LVM were treated with OK-432. The majority of the lesions were macrocystic (69 %), microcystic (19 %) and mixed (12 %). From the total number of patients, 11 fully healed, and 72 % of the study population had >50 % reduction in lesion size, with only 2 applications. There were no recurrences. Complications were reported in 2 patients who had skin hyperpigmentation.
CONCLUSIONS
OK-432 probed to be an effective treatment for LVM in a reference hospital in the north of Mexico.
Topics: Antineoplastic Agents; Female; Humans; Hyperpigmentation; Lymphangioma; Lymphatic Abnormalities; Male; Mexico; Picibanil; Retrospective Studies; Treatment Outcome
PubMed: 29658945
DOI: 10.24875/BMHIM.M18000013 -
Reproductive Sciences (Thousand Oaks,... Feb 2019In advanced ovarian cancer, traditional therapy included debulking surgery and postoperative chemotherapy. We proposed immunochemotherapy (IMCT) combined with picibanil...
OBJECTIVE
In advanced ovarian cancer, traditional therapy included debulking surgery and postoperative chemotherapy. We proposed immunochemotherapy (IMCT) combined with picibanil (OK-432), interleukin-2 (IL-2), and traditional platinum- and taxol-based chemotherapy as a better treatment option for advanced ovarian cancer.
METHODS
We retrospectively reviewed the medical records of 51 patients with advanced ovarian cancer between 2007 and 2015 at Chang Gung Memorial Hospital Linkou Medical Center, including 26 patients who were treated with OK-432, IL-2, and platinum- and taxol-based chemotherapy (IMCT group) after debulking surgery; another 25 were treated with traditional platinum- and taxol-based chemotherapy (traditional chemotherapy group) after debulking surgery. We analyzed the difference in age, follow-up period, recurrence rate, and diagnosis-to-recurrence period between the 2 groups. We also analyzed the difference in complete blood cell counts, differentiating counts, and cancer antigen 125 (CA-125) at 1 month after treatment.
RESULTS
The recurrence rate between the IMCT and traditional chemotherapy groups showed a significant difference (53.8% vs 88%; P = .0128). The diagnosis-to-recurrence duration was longer in the IMCT than in the traditional chemotherapy groups (33.21 vs 25.63 months), although no statistical significance was found ( P = .4668). In laboratory analysis at 1 month after treatment, the white blood cell, absolute neutrophil, and absolute lymphocyte counts (ALCs) were significantly higher in the IMCT group. On the other hand, CA-125 was significantly lower, and ALC was significantly higher in the nonrecurrence group.
CONCLUSIONS
Combined IMCT and chemotherapy have lower recurrence rate compared to traditional chemotherapy after debulking surgery for the treatment of advanced ovarian cancer.
Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Female; Humans; Immunotherapy; Interleukin-2; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Ovarian Neoplasms; Picibanil; Retrospective Studies; Treatment Outcome
PubMed: 29658435
DOI: 10.1177/1933719118768684 -
Anticancer Research Apr 2018Wilms' tumor 1 (WT1) peptide-based vaccination has been reported for its potential usefulness in targeting several cancers. The adjuvant drug OK-432 is known to have... (Clinical Trial)
Clinical Trial
BACKGROUND/AIM
Wilms' tumor 1 (WT1) peptide-based vaccination has been reported for its potential usefulness in targeting several cancers. The adjuvant drug OK-432 is known to have potent immunomodulation and therapeutic properties when applied in cancer treatment and may, thus, be important to trigger the appropriate immunological response in paediatric patients with a solid tumor that are vaccinated with a WT1 peptide.
PATIENTS AND METHODS
Paediatric patients with a solid tumor were vaccinated with a WT1 peptide and OK-432 once every 2 weeks, for a total of seven times.
RESULTS
Of the 24 patients, 18 completed the scheduled vaccinations. Sixteen patients had local skin symptoms and/or fever. In 1 patient, anaphylactic symptoms emerged at the time of the final injection, but these quickly subsided after the treatment. WT1-specific immunological responses were observed in 4 patients (22.2%). WT1 and HLA class I expression were confirmed in 100% and 85% of primary tumors, respectively.
CONCLUSION
WT1 peptide vaccine therapy combined with OK-432 appears to be relatively safe for children. However further studies in a larger number of patients are necessary to confirm its safety and efficacy.
Topics: Adjuvants, Immunologic; Adolescent; Adult; Cancer Vaccines; Child; Child, Preschool; Feasibility Studies; Female; Humans; Immunity, Innate; Male; Neoplasms; Picibanil; Treatment Outcome; Vaccination; WT1 Proteins; Young Adult
PubMed: 29599343
DOI: 10.21873/anticanres.12465