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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 -
British Journal of Cancer May 2002Both 5-fluorouracil and doxorubicin are commonly used agents in chemotherapy of gastric cancer in adjuvant setting as well as metastatic disease. In a variety of... (Comparative Study)
Comparative Study
Expression of multidrug resistance-associated protein1,P-glycoprotein, and thymidylate synthase in gastric cancer patients treated with 5-fluorouracil and doxorubicin-based adjuvant chemotherapy after curative resection.
Both 5-fluorouracil and doxorubicin are commonly used agents in chemotherapy of gastric cancer in adjuvant setting as well as metastatic disease. In a variety of malignancies, high expression of multidrug resistance-associated protein1 and P-glycoprotein has been associated with resistance to doxorubicin, whereas 5-fluorouracil resistance has correlated with the level of thymidylate synthase expression. We evaluated the expression of multidrug resistance-associated protein1, P-glycoprotein, and thymidylate synthase using immunohistochemistry in 103 locally advanced gastric cancer patients (stage IB-IV) who underwent 5-fluorouracil and doxorubicin-based adjuvant chemotherapy after curative resection and investigated the association between their expression and clinicopathologic characteristics including prognosis of the patients. While high expression (> or =5% of tumour cells positive) of multidrug resistance-associated protein1 and P-glycoprotein was observed in 70 patients (68%) and 42 patients (41%), respectively, 65 patients (63%) had primary tumours with high expression (> or =25% of tumour cells positive) of thymidylate synthase. There was a significant association between multidrug resistance-associated protein1 and P-glycoprotein expression (P<0.0001) as well as P-glycoprotein and thymidylate synthase expression (P<0.0001). High multidrug resistance-associated protein1 and P-glycoprotein expressions were associated with well and moderately differentiated histology (P<0.0001 and P=0.03, respectively) and intestinal type (P<0.0001 and P=0.009, respectively). High multidrug resistance-associated protein1 expression correlated with lymph node metastasis (P=0.037), advanced stage (P=0.015), and older age (P=0.021). Five-year disease-free survival and overall survival of total patients were 55.2% and 56.2%, respectively, with a median follow-up of 68 months. There were no significant differences in disease-free survival and overall survival according to the expression of multidrug resistance-associated protein1 (P=0.902 and P=0.975, respectively), P-glycoprotein (P=0.987 and P=0.955, respectively), and thymidylate synthase (P=0.604 and P=0.802, respectively). Concurrent high expression of these proteins (high multidrug resistance-associated protein1/P-glycoprotein, high multidrug resistance-associated protein1/thymidylate synthase, high P-glycoprotein/thymidylate synthase) did not correlate with disease-free survival or overall survival. Even high expression of all three proteins was not associated with poor disease-free survival (P=0.919) and overall survival (P=0.852). In conclusion, high expression of multidrug resistance-associated protein1, P-glycoprotein, and thymidylate synthase did not predict poor prognosis of gastric cancer patients treated with 5-fluorouracil and doxorubicin-based adjuvant chemotherapy. A larger study including patients treated with surgical resection alone would be necessary.
Topics: ATP Binding Cassette Transporter, Subfamily B, Member 1; Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Combined Modality Therapy; Disease-Free Survival; Doxorubicin; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Female; Fluorouracil; Gastrectomy; Humans; Immunotherapy; Lentinan; Life Tables; Male; Middle Aged; Mitomycin; Neoplasm Proteins; Picibanil; Stomach Neoplasms; Survival Analysis; Thymidylate Synthase
PubMed: 12085207
DOI: 10.1038/sj.bjc.6600305 -
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 -
Cancer Immunology, Immunotherapy : CII Mar 1994An important objective for patients with unresectable hepatocellular carcinoma (HCC) is the development of effective chemotherapy. We administered a combination of... (Clinical Trial)
Clinical Trial
An important objective for patients with unresectable hepatocellular carcinoma (HCC) is the development of effective chemotherapy. We administered a combination of biological response modifiers and anticancer agents to 24 patients with unresectable HCC. Each case had an implanted infuser port which was connected to a catheter placed in the hepatic artery for the intraarterial (i.a.) administration of chemotherapy. The following agents were administered to each patient: recombinant interleukin-2 (800,000 JRU/day infused i.a. continuously for 6 days/week); OK-432 (5 KE injected i.a. twice in 4 weeks and i.m. three times per week); Adriamycin (10 mg injected i.a. twice in 4 weeks); cyclophosphamide (300 mg injected i.a. twice in 4 weeks), and famotidine (40 mg/day administered orally). Objective response was assessed according to tumor size measured by computed tomography and angiography before and after treatment. We observed a complete response (CR) in 4, partial response (PR) in 3, minor response (MR) in 7, no change (NC) in 7, and progressive disease (PD) in 3. The response rate (CR+PR+MR) was 58.3%. The overall 2-year survival rate was 52%. The 2-year survival rate of the responders (CR+PR+MR) was 80%, while that of the non-responders (NC+PD) was 0%. There was a significant difference between the responders and non-responders in respect to survival rate (P < 0.05). The percentages of CD25+ cells, CD56+ cells, and Leu7-CD16+ cells and NK activity in the peripheral blood showed a significant increase following the regimen. Serum levels of tumor necrosis factor alpha TNF alpha rose after the initiation of OK-432. TNF alpha levels were higher in the responders than in the non-responders. Adverse effects included high fever (all patients) and severe transient hypotension (15 patients) that was controlled by conservative therapy. Combined immunochemotherapy administered intraarterially may be a new strategy for treating unresectable HCC.
Topics: Aged; Carcinoma, Hepatocellular; Combined Modality Therapy; Cyclophosphamide; Doxorubicin; Famotidine; Female; Humans; Immunity, Cellular; Immunotherapy; Interleukin-2; Killer Cells, Natural; Liver Neoplasms; Lymphocyte Subsets; Male; Middle Aged; Picibanil; Survival Analysis; Tumor Necrosis Factor-alpha
PubMed: 8124688
DOI: 10.1007/BF01525641 -
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 -
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 -
Scientific Reports Jun 2020Treatment options for metastatic osteosarcoma are limited. The present study aimed to evaluate whether radiofrequency ablation (RFA) combined with intratumoural OK-432...
Treatment options for metastatic osteosarcoma are limited. The present study aimed to evaluate whether radiofrequency ablation (RFA) combined with intratumoural OK-432 injection induces systemic anti-tumour immunity in rat osteosarcoma model. Eighty of 145 rats were assigned to four groups to evaluate overall survival and tumour size: control (no treatment), RFA-only, OK-432, and RFA-OK-432. The remaining 65 were assigned for histological examination. Maximum diameters of tibial and lung tumours were determined. Tumour samples were histologically examined using haematoxylin-eosin and immunohistochemical staining. Overall survival was significantly prolonged in the RFA-OK-432 group compared to the RFA-only and OK-432 groups. Only rats in the RFA-OK-432 group exhibited significant decreases in maximum tumour diameter after treatment. Ki-67-positive tumour cells in the RFA-OK-432 group were significantly stained negative on immunohistochemical analysis as opposed to those in the RFA-only and OK-432 groups. The number of CD11c+, OX-62+, CD4+, and CD8 + cells significantly increased in the RFA-OK-432 group compared to the RFA-only group. RFA with intratumoural OK-432 injection resulted in distant tumour suppression, prolonged survival, and increased dendritic cells, cytotoxic T cells, IFN-γ, and TNF-α, whereas RFA or OK-432 alone did not produce this effect. This combination may induce an abscopal effect in human osteosarcoma.
Topics: Animals; Antineoplastic Agents; Bone Neoplasms; Cell Line, Tumor; Combined Modality Therapy; Osteosarcoma; Picibanil; Radiofrequency Ablation; Rats; Treatment Outcome; Tumor Burden; Xenograft Model Antitumor Assays
PubMed: 32541941
DOI: 10.1038/s41598-020-66934-6 -
The Tohoku Journal of Experimental... Jun 1990A 70-year-old man having severe ischemic heart diseases developed bilateral, duplicate lung cancer of large cell and squamous cell types. Chemoimmunotherapy consisting...
A 70-year-old man having severe ischemic heart diseases developed bilateral, duplicate lung cancer of large cell and squamous cell types. Chemoimmunotherapy consisting of carmofur, picibanil inhalation, i.m. sizofilan, and peroral bestatin was started, and 3 months later, peroral medroxyprogesterone acetate was added. The tumor regressed, and the patient survived more than 34 months. This type of nonaggressive regimen may thus be useful for tumors other than adenocarcinomas, too.
Topics: Aged; Antineoplastic Agents; Carcinoma, Squamous Cell; Humans; Lung Neoplasms; Male; Medroxyprogesterone; Medroxyprogesterone Acetate; Radiography
PubMed: 2148230
DOI: 10.1620/tjem.161.153 -
The Tohoku Journal of Experimental... Jul 1987The IFN producing activity of RLNL and PBL was studied in cancer patients using K562, PHA-P and OK-432 as inducers. In response to K562, IFN production was significantly...
The IFN producing activity of RLNL and PBL was studied in cancer patients using K562, PHA-P and OK-432 as inducers. In response to K562, IFN production was significantly greater in the PBL than in the RLNL, and the titer was about equal in the PBL and RLNL when OK-432 was used as an inducer. On the contrary, the amount of IFN produced by PHA-P was significantly higher in the RLNL than in the PBL. There was no definite relationship recognized between tumor progression and IFN productivity in the cases studied.
Topics: Adult; Aged; Cell Line; Colonic Neoplasms; Female; Humans; Interferons; Leukemia, Erythroblastic, Acute; Lymph Nodes; Lymphocytes; Male; Middle Aged; Phytohemagglutinins; Picibanil; Rectal Neoplasms; Stomach Neoplasms
PubMed: 2444014
DOI: 10.1620/tjem.152.231 -
Hinyokika Kiyo. Acta Urologica Japonica Sep 1984Four patients with urinary bladder carcinoma were treated by combination therapy which consisted of hyperthermia vesical irrigation of two anticancer drugs (peplomycin...
Four patients with urinary bladder carcinoma were treated by combination therapy which consisted of hyperthermia vesical irrigation of two anticancer drugs (peplomycin and picibanil), intravesical instillation of those drugs and radiation. Following the therapeutic method we planned, 40 mg of peplomycin and 10 KE of picibanil in 1,500 ml of sterile distilled water was irrigated at 42 to 43 degrees C into the bladder for 3 hours; 40 mg of peplomycin and 10 KE of picibanil in 40 ml of sterile distilled water was instilled into the bladder; and, the focus was irradiated with 60Co to a focal dose of 200 rad 30 minutes later. This pattern of treatment was repeated once a week, 3 to 5 times in total. On the days this pattern was not taken, 5 KE of picibanil in 20 ml of sterile distilled water was instilled into the bladder cavity. Complete response was observed in one patient and partial response in 3 patients. The side effect was temporary irritable bladder symptom.
Topics: Aged; Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carcinoma, Transitional Cell; Combined Modality Therapy; Female; Humans; Hyperthermia, Induced; Male; Middle Aged; Peplomycin; Picibanil; Radiotherapy Dosage; Urinary Bladder Neoplasms
PubMed: 6084419
DOI: No ID Found