picibanil and Pancreatic-Neoplasms

To determine the feasibility, safety and histological change of preoperative endoscopic ultrasound-guided fine-needle injection (PEU-FNI) of immature DCs (iDCs) with OK-432 in pancreatic cancer patients.. Nine patients enrolled in the trial (DC group) and were compared with 15 patients operated on without iDC injection (non-DC group). Adverse events of PEU-FNI and postoperative complications were evaluated according to CTC-AE ver.3.0 and the Clavien-Dindo classification/ISGPF definition, respectively. Histological changes within the tumor and lymph nodes were evaluated by immunohistochemical examination of infiltrating inflammatory cells (CD4+, CD8+, Foxp3+ and CD83+).. There were no severe toxicities following PEU-FNI, except for one transient grade 3 fever, and there were no significant differences in the incidence of postoperative complications between the two groups. Colliquative necrosis and diffusely scattered TUNEL-positive cells were observed at the injection sites. CD83+ cells significantly accumulated in the regional lymph nodes of the DC group as well as Foxp3+ cells in the regional and distant lymph nodes. The two DC group patients, one of which was stage IV with distant lymph node metastasis, survived more than 5 years without requiring adjuvant theraphy.. PEU-FNI was feasible and safe, and further study needs to confirm and enhance antitumor responses.

Topics: Adenocarcinoma; Aged; Antineoplastic Agents; Combined Modality Therapy; Dendritic Cells; Endoscopic Ultrasound-Guided Fine Needle Aspiration; Feasibility Studies; Female; Humans; Immunohistochemistry; Injections, Intralesional; Lymph Nodes; Lymphocytes, Tumor-Infiltrating; Male; Middle Aged; Pancreatic Neoplasms; Picibanil; Preoperative Period

Greenway et al reported estrogen receptor existed in the carcinoma of the exocrine pancreas in 1981. We followed the study by using immunohistochemical method with monoclonal antibody ER-D5 (Amersham) and found high levels of estrogen receptor in 21 cases out of 27 carcinomas of the pancreas (77.8%). Furthermore, we gave randomly the hormone therapy by Tamoxifen 20 mg per day adding to immuno-chemotherapy (Tegaful, Mitomycin, Krestin, OK-432) to the patients with resected carcinoma of the pancreas. There was no significant difference of the survival rate of pancreatic carcinoma without hormone therapy between 10 cases with estrogen receptor and 4 cases without estrogen receptor at the 6th month and 12th month. However, in cases treated by Tamoxifen, remarkable high survival rate at 12 months of 11 cases with estrogen receptor was obtained to be 85.7% according to Kaplan-Meier method. Two cases without estrogen receptor died within 5 months. One year survival rate of Tamoxifen group (13 cases) was 78.6% and that of non Tamoxifen group (14 cases) was 21.4%. These findings indicated that estrogen receptor existed at the high level in the carcinoma tissues of the pancreas and anti-estrogen treatment might offer a new approach to the treatment of pancreatic carcinomas.

Topics: Adult; Aged; Chemotherapy, Adjuvant; Combined Modality Therapy; Female; Humans; Male; Middle Aged; Mitomycins; Pancreatectomy; Pancreatic Neoplasms; Picibanil; Proteoglycans; Receptors, Estrogen; Survival Rate; Tamoxifen; Tegafur

The effective treatment of unresectable pancreatic cancer remains to be elucidated. We report herein a patient who underwent a local injection of a mixture of OK-432, fibrinogen and thrombin. Tumor size and tumor markers significantly decreased following this procedure. Local injection therapy with OK-432, fibrinogen and thrombin may be a promising treatment for unresectable pancreatic cancer.

Topics: Adenocarcinoma; Drug Therapy, Combination; Fibrinogen; Humans; Injections, Intralesional; Pancreatic Neoplasms; Picibanil; Thrombin

Effect of lymphokine activated killer (LAK) cells induced by in vitro or in vivo stimulation with biological response modifier (BRM) such as recombinant interleukin-2 (rIL-2) or OK-432 on the growth of pancreatic cancer cells injected into nude mice were studied. Human rIL-2 stimulated spleen cells from BALB/c nu/nu mice were used as effector LAK cells. Human pancreatic cancer cell lines PK-1 and PK-9 were used as target for cytolytic activities against pancreatic cancer. Cytolysis was estimated by 51Cr release assay in vitro, and tumor growth inhibition was estimated by Winn assay in vivo. NK, LAK and pancreatic cancer cell killing activities of LAK cells were elevated to significantly high level of 82%, 70% 51% (PK-1) and 33% (PK-9) respectively on the 2nd day after cultivation with rIL-2. Significantly high level of tumor inhibition rate (98%) was obtained when PK-1 cells were injected into nude mice subcutaneously with LAK cells compared with injection of PK-1 cells only (control). Spleen cells induced from nude mice injected intraperitoneally with rIL-2 or OK-432 showed significantly high cytolytic activities. These results indicate that LAK cells induced by in vitro or in vivo stimulation with BRM could inhibit the growth of pancreatic cancer.

Topics: Animals; Humans; Immunotherapy, Adoptive; Interleukin-2; Killer Cells, Lymphokine-Activated; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Transplantation; Pancreatic Neoplasms; Picibanil; Recombinant Proteins

Although 58 patients with peritonitis carcinomatosa underwent multidisciplinary therapy over the last 5 years in our department, about half of them died within 3 months after treatment. In addition, the prognosis was poor for gastric and colon cancer patients, who had macroscopic peritoneal dissemination. Therefore intraoperative intraperitoneal administration of either BRM or anticancer drugs was performed for the microscopic peritoneal dissemination of the cancer, and the immunological response in the peritoneal cavity was examined. In terms of subpopulation of peritoneal exudate cells, neutrophil leucocytes were predominant and thereafter lymphocytes increased. As for the cytokines in the exudate from peritoneal cavity, the concentration of interleukin-6 peaked within 24 hours after administration, followed by a gradual decrease, while the concentration of interferon-gamma was detectable at more than 24 hours after operation, followed by a gradual increase. Tumor necrosis factor-alpha was also detectable in the exudate. Its concentration decreased when both OK-432 and MMC were administered, but it increased when CDDP was administered. The above results indicated that preventive intraoperative intraperitoneal administration of BRM and anticancer drugs should bring about individual immunokinetic modulation in tumor bearing host and both cytokines and immunocytes could play an important role in locoregional tumor immunity.

Topics: Cisplatin; Humans; Immunotherapy; Infusions, Parenteral; Mitomycin; Pancreatic Neoplasms; Peritonitis; Picibanil; Stomach Neoplasms

The endogenous induction of tumor necrosis factor serum (TNS) for cancer immunotherapy was undertaken in the immediate postoperative period using Lentinan as the primer and OK-432 as the inducer. The changes in several immunological markers of the blood were assayed and compared with a control group to clarify the effects of this treatment. Plasma TNF-alpha levels were elevated two to three hours after eliciting treatment. The neutrophil count was elevated on the 7th postoperative day (POD) and the natural killer (NK) cell activity was transiently suppressed on the 1st POD, but NK cells possessing a high activity (Leu7-CD16+) were preserved until the 7th POD. Helper/inducer (CD4+) and killer cells (CD8+ CD11-) tended to increase, and suppressor (CD8 bright+ CD11+) cells tended to decrease in the induction group. There was no difference in the levels of prostaglandin E2 (PGE2) between the groups, but a marked elevation of interferon-gamma was evident on the 1st POD in the induction group. This treatment may be useful as postoperative adjuvant immunotherapy for cancer due to its ability to induce cytokines and activate host immune mechanisms.

Topics: Aged; Antigens, CD; Biomarkers, Tumor; Carcinoma, Hepatocellular; CD4-Positive T-Lymphocytes; Esophageal Neoplasms; Female; Humans; Immunotherapy; Interferons; Lentinan; Leukocyte Count; Liver Neoplasms; Male; Middle Aged; Pancreatic Neoplasms; Picibanil; Postoperative Period; Remission Induction; Stomach Neoplasms; T-Lymphocytes, Regulatory; Tumor Necrosis Factor-alpha

Using the Su-PS skin test, an attempt was made to evaluate whether or not this reaction could become a useful immune parameter in patients with gastrointestinal cancer. The conclusions were as follows: Late-stage patients with gastric cancer showed a weak response in the Su-PS skin test when examined preoperatively. The skin reaction to Su-PS was shown to become stronger than in the PPD and PHA test when patients received OK-432 treatment. Patients with advanced cancer having longer survival (more than 7 months) showed stronger response in the Su-PS skin test that patients having short survival (less than 6 months). It was suggested that the Su-PS skin test was useful for evaluating the immune response to OK-432 treatment.

Topics: Biological Products; Colonic Neoplasms; Esophageal Neoplasms; Humans; Intradermal Tests; Pancreatic Neoplasms; Phytohemagglutinins; Picibanil; Polysaccharides, Bacterial; Skin Tests; Stomach Neoplasms; Tuberculin Test

Topics: Aged; Biological Products; Female; Humans; Injections; Male; Middle Aged; Pancreatic Neoplasms; Picibanil

Topics: Aged; Biological Products; Biopsy, Needle; Female; Gallbladder Neoplasms; Humans; Male; Middle Aged; Pancreatic Neoplasms; Picibanil; Ultrasonography

Topics: Aged; Antineoplastic Agents; Chemotherapy, Cancer, Regional Perfusion; Female; Humans; Male; Middle Aged; Pancreatic Neoplasms; Picibanil; Ultrasonography

Topics: Adult; Aged; Biological Products; Female; Humans; Male; Middle Aged; Pancreatic Neoplasms; Picibanil; Punctures; Ultrasonography

Topics: Aged; Biological Products; Drug Therapy, Combination; Female; Fluorouracil; Humans; Intestinal Neoplasms; Lung Neoplasms; Male; Middle Aged; Neoplasms; Pancreatic Neoplasms; Picibanil; Stomach Neoplasms; Tegafur