picibanil and Peritoneal-Neoplasms

The effects of postoperative immunochemotherapy including the streptococcal preparation OK-432 on the rate of peritoneal recurrence and survival time after curative resection were studied in 36 patients with gastric cancer. Patients randomized to group B received 18 months of a therapy that is widely used in Japan for patients with gastric cancer: mitomycin C (MMC) and UFT, a combination of tegafur and uracil in a molar ratio of 1:4. Patients randomized to group A received the same drugs given to group B plus an intraperitoneal injection of OK-432 on postoperative day 0 and intradermal injections of OK-432 for 18 months at 2-week intervals. There were no differences between the two groups in any known prognostic factor or dose of any drug received, except for OK-432. There was no difference in the toxicity rates between the groups. The concomitant administration OK-432 and anticancer drugs significantly decreased the rates of peritoneal recurrence and lengthened survival time (P < 0.05).

Topics: Adjuvants, Immunologic; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Drug Administration Schedule; Female; Gastrectomy; Humans; Injections, Intradermal; Injections, Intraperitoneal; Male; Middle Aged; Mitomycin; Neoplasm Recurrence, Local; Neoplasm Staging; Peritoneal Neoplasms; Picibanil; Postoperative Care; Prognosis; Prospective Studies; Stomach Neoplasms; Survival Rate; Tegafur; Treatment Outcome; Uracil

We studied the effects on survival time of postoperative immuno-chemotherapy, including the streptococcal preparation OK-432, in patients with gastric cancer and synchronous peritoneal dissemination. The patients were prospectively randomized and a valid statistical assessment could be made for 109. Patients randomized to group B received therapy that is widely used in Japan to treat patients with gastric cancer: mitomycin C (MMC) and UFT, a combination of tegafur and uracil in a molar ratio of 1:4, for 1 year. Patients randomized to group A received the same drugs as were given to group B patients plus OK-432 i.p. for 7 days, beginning on postoperative day 0, and OK-432 by intradermal injection for 1 year, at 2-week intervals. There were no differences between the two groups in any known prognostic factor or in the dose of any drug administered except for OK-432. There was no difference in the toxicity rate between the groups. In this negative trial, there was no improvement in survival time with the addition of OK-432 to MMC and UFT for patients with gastric cancer and peritoneal dissemination.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Drug Administration Schedule; Female; Humans; Injections, Intradermal; Injections, Intraperitoneal; Male; Middle Aged; Multivariate Analysis; Peritoneal Neoplasms; Picibanil; Prospective Studies; Stomach Neoplasms; Survival Analysis; Treatment Outcome

The greater omentum contains abundant lymphoid tissues composed of a lot of macrophages and lymphocytes, and plays an important role in a host defense system in the peritoneal cavity. Also, it is well known to be an initial site of peritoneal disseminated metastases. We experienced a rare case of a 60-year-old man with postoperative recurrence of esophageal cancer that presented itself in the greater omentum of the gastric tube reconstructed through a mediastinal route, as well as through mediastinal lymph-nodes. We performed CT-guided radiofrequency ablation (RFA) for recurrent omental tumor that was refractory to chemoradiation therapy and growing rapidly adjacent to the trachea. In combination with local control using RFA, we attempted a systemic immunotherapy using OK-432, by subcutaneous injection around RFA to accelerate host antitumor immune responses induced by antigen stimulation by RFA, based on the immunological property of the omentum. RFA induced a significant therapeutic effect on the omental tumor with massive necrotic change. However, no apparent size reduction was seen in the metastatic mediastinal lymph nodes, although an increase of peripheral blood lymphocytes was observed before and after RFA, and systemic host immune responses were stimulated by OK-432.

Topics: Antineoplastic Agents; Catheter Ablation; Esophageal Neoplasms; Esophagoplasty; Humans; Immunotherapy; Male; Mediastinal Neoplasms; Middle Aged; Omentum; Peritoneal Neoplasms; Picibanil

To evaluate the efficacy of a streptococcal preparation, OK432, on malignant ascites in mice.. PC-C203U (PC203) is a preparation of another strain of the streptococcal family, with the lowest antineoplastic action. To examine the survival curves of mice after the inoculation of BAMC-1 tumor cells, we gave intraperitoneal OK432, PC203, or saline as a control. Intraperitonal neutrophils were counted by cytospin, and interleukin-1beta (IL-1beta), interleukin-6 (IL-6), and macrophage inflammatory protein (MIP)-1alpha were measured by enzyme-linked immunosorbent assay, and 8 h after the administration of OK432, PC203, and saline. Using electron microscopy, we examined the greater omental milky spots, where the in situ proliferation of neutrophils or macrophages takes place.. The OK432 group had the best survival and the control group the worst. The ratio of intraperitoneal neutrophils to BAMC-1 was highest in the OK432 group and lowest in the control group. Quantitative IL-1beta, IL-6 and MIP-1alpha levels were correlated closely with survival. Electron microscopic examination of the milky spots revealed massive proliferation of neutrophils in the OK432 group, but not in the PC203 or control groups.. OK432 effectively activated intraperitoneal neutrophils and a series of immunological chain reactions through an increase in IL-1beta, IL-6, and MIP-1alpha levels. Milky spots could have important antitumor effects in terms of the spread of neutrophils.

Topics: Animals; Ascites; Cell Line, Tumor; Cytokines; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Female; Mice; Mice, Inbred BALB C; Neoplasm Transplantation; Neutrophils; Peritoneal Neoplasms; Picibanil; Probability; Random Allocation; Reference Values; Sensitivity and Specificity

A case of malignant mesothelioma of the peritoneum successfully treated with short-term intraperitoneal chemotherapy is reported. A 67-year-old woman underwent laparotomy for ascending colon cancer. During, laparotomy, numerous mucoid nodules were found on the peritoneal surface, even though the colonic tumor did not invade the serosa. Ileocecal resection (D1) with partial omentectomy was performed. Intraperitoneal infusion with cisplatin (200 mg) was started immediately after surgery and additional cisplatin (150 mg) was administered with OK-432 (30KE). The serum level of CA125 rapidly decreased after the chemotherapy, and was normalized 3 months postoperatively. The histological diagnosis of the peritoneal lesions was malignant mesothelioma of the peritoneum (diffuse type). The patient is living without any evidence of recurrence 10 months postoperatively. These results suggest that this short-term chemotherapy is worth trying in cases of malignant mesothelioma of the peritoneum.

Topics: Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Female; Humans; Infusions, Parenteral; Mesothelioma; Peritoneal Neoplasms; Picibanil

We evaluated intraperitoneal cytology during surgery as a significant predictor of survival and tried to establish strategies for preventing peritoneal carcinomatosis.. The study included 236 patients with gastric carcinoma macroscopically invading the serosa who underwent intraperitoneal cytological examination during surgery. In the 215 resected patients, the relationship between cytological positivity for cancer cells and various clinicopathologic features was analyzed. Additionally, postoperative survival was assessed in relation to the positivity of intraoperative cytology.. Cancer cells were positive [Cy+] in 78 (33.1%) of 236 patients who underwent cytological examinations. Among 73 patients with peritoneal metastases, 53 patients (72.6%) were Cy+, as were 25 (15.3%) of the 163 patients without peritoneal metastases. Multivariate analysis indicated that peritoneal metastasis (p = 0.0001) and the depth of tumor invasion (p = 0.0069) were significant factors correlated with Cy+. Among patients with curative surgery, the 5-year survival rate of the Cy+ group was 22.2%, which was worse (p = 0.0004) compared with that of the Cy(-) group (60.9%). Among Cy+ patients, the survival rate of the group treated with intraperitoneal administration of mitomycin C (MMC) and OK-432 was better (p = 0.0108) than that of the historical control group.. These results suggest that intraperitoneal cytological examination can be a significant prognostic factor for gastric carcinoma with serosal invasion. In addition, dissemination of cancer cells in the peritoneum may be controlled by intraperitoneal immunochemotherapy with MMC and OK-432.

Topics: Adenocarcinoma; Adenocarcinoma, Mucinous; Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Carcinoma, Signet Ring Cell; Combined Modality Therapy; Female; Gastrectomy; Humans; Intraoperative Care; Liver Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Mitomycin; Peritoneal Cavity; Peritoneal Neoplasms; Picibanil; Postoperative Care; Stomach Neoplasms; Survival Rate

Prognostic factors, such as preoperative status, intraoperative findings, and postoperative treatments, were evaluated in 61 patients with peritoneal metastasis from gastric cancer treated in our facility between 1979 and 1991. Since 1986, 23 patients have been treated with OK-432-combined adoptive immunotherapy (AIT). OK-432-combined AIT is a sequential treatment via a catheter inserted into the abdominal cavity, using a streptococcal preparation, OK-432, followed by the transfer of lymphocytes cultured with T cell growth factor and sonicated tumor extract. A univariate analysis showed that six factors consisting of: (1) age, (2) resection of primary lesion, (3) grade of peritoneal metastasis or serosal invasion, (4) chemotherapy, (5) OK-432, and (6) OK-432-combined AIT influenced survival. The survival of the patients given OK-432-combined AIT (median survival time; MST = 7.5 months) was significantly (P = 0.0267) longer than that of those not receiving OK-432-combined AIT (MST = 4.3 months). A multivariate analysis showed that the most significant factors associated with survival were chemotherapy, resection of the primary lesion, and OK-432-combined AIT. Since these three factors are all therapeutic procedures, the use of combination therapy including OK-432-combined AIT is thus expected to prolong the survival of gastric cancer patients with peritoneal metastasis.

Topics: Adult; Aged; Aged, 80 and over; Combined Modality Therapy; Female; Humans; Immunotherapy, Adoptive; Male; Middle Aged; Peritoneal Neoplasms; Picibanil; Prognosis; Regression Analysis; Retrospective Studies; Stomach Neoplasms; Survival Rate

In order to improve the prognosis, intraoperative intraperitoneal administration of both mitomycin C and OK-432 was performed for the peritoneal dissemination of gastric cancer. Some 74 of 469 patients of gastric cancer, who underwent surgical treatment over the last 7 years in our department, had peritoneal dissemination and 24 of them were treated with the drugs described above. However, there was no significant difference between treated group and controlled untreated group. No severe side effects were noted except for moderate pyrexia. It is still too early to determine the effect of this treatment because of both the short duration of follow-up and the small number of analyzed cases. In the future, we are planning to apply this treatment to selected cases, for which a histological diagnosis will be made intraoperatively by use of irrigation cytology and/or stamp biopsy.

Topics: Adult; Aged; Biological Products; Female; Gastrectomy; Humans; Infusions, Parenteral; Intraoperative Care; Male; Middle Aged; Mitomycin; Mitomycins; Neoplasm Seeding; Peritoneal Neoplasms; Picibanil; Prognosis; Stomach Neoplasms; Survival Rate

In patients with gastric cancer invading the serosa, there is often peritoneal dissemination. In an attempt to control such peritoneal recurrences, OK-432, a compound composed of penicillin G-treated, attenuated Streptococcus pyogens of human origin, was administered intraperitoneally at the time of gastrectomy. The non-specific antitumor activity of the peritoneal macrophages was investigated for its cytostatic activity against the cultured human lung cancer cell line, QG-90. OK-432 given intraperitoneally significantly increased the number of the peritoneal macrophages (p less than 0.05), and also enhanced the cytostatic activity (p less than 0.01). On the basis of these findings, OK-432 IP after gastrectomy was given to 13 of 68 patients with gastric cancer invading the serosa and who underwent curative resection. The five-year survival rate of patients given the drug was 63.5%, while the rate was 52.9% in those not given the drug. OK-432 IP seemed to be effective when lymph node involvement was nil or limited to around the area of the stomach. The peritoneal recurrence rate was, however, not affected by OK-432 IP. Elevation of body temperature and some dehydration were the only observed side effects of OK-432. In attempts to control peritoneal recurrences in patients with gastric cancer invading the serosa, randomized controlled trials on OK-432 IP are now being designed.

Topics: Adenocarcinoma; Cell Count; Cytotoxicity, Immunologic; Gastrectomy; Humans; Intraoperative Period; Macrophages; Peritoneal Lavage; Peritoneal Neoplasms; Phagocytosis; Picibanil; Stomach Neoplasms

Twenty-four patients with advanced stomach cancer were treated with OK-432 combined adoptive immunotherapy [AIT] as prophylaxis or therapy against peritoneal metastases. Lymphocytes isolated mainly from regional lymph nodes were cultured for 9-13 days with T cell growth factor and sonicated tumor extract. OK-432 administration and cell transfer were performed via a catheter inserted into the abdominal cavity at surgery. The proliferation rate of regional lymph node lymphocytes was higher than that of peripheral blood lymphocytes (p less than 0.01). Cultured regional lymph node lymphocytes expressed CD25 and CD4+45R- more frequently than those of peripheral blood lymphocytes. On the other hand, cytotoxic activity of regional lymph node lymphocytes were slightly lower than that of peripheral blood lymphocytes. These results suggest that regional lymph node lymphocytes could be used in AIT because of their different function from that of peripheral blood lymphocytes. Survival of the patients with peritoneal metastasis at primary laparotomy was higher than that of the historical control group (4-9 months after surgery). These results show that OK-432 combined adoptive immunotherapy appears to be a new therapeutic approach to peritoneal metastases from stomach cancer.

Topics: Adult; Aged; Aged, 80 and over; Female; Humans; Immunization, Passive; Killer Cells, Lymphokine-Activated; Lymph Nodes; Lymphocyte Activation; Male; Middle Aged; Peritoneal Neoplasms; Picibanil; Stomach Neoplasms

Protective effect of OK-432 on peritoneal recurrence was examined in an experimental mouse model with Meth A fibrosarcoma injected into both abdominal wall and intraperitoneal cavity. OK-432 was given through either intratumoral (i.t.), intradermal (i.d.), intraperitoneal (i.p.), or i.p. + i.t. route. A significant antitumor effect against abdominal tumor was observed in mice given i.t. or i.p. + i.t. injection of OK-432. A significant protective effect against peritoneal recurrence and prolonged survival time was obtained in an i.p. + i.t. group, although other treatment groups showed only minimal effect. We conclude that combined i.p. and i.t. administration of OK-432 may prevent peritoneal recurrence and lead to prolongation in clinical patients with advanced GI tract cancer.

Topics: Animals; Biological Products; Female; Fibrosarcoma; Injections, Intralesional; Injections, Intraperitoneal; Mice; Mice, Inbred BALB C; Peritoneal Neoplasms; Picibanil; Prognosis; Sarcoma, Experimental

Recombinant interleukin-2 (rIL-2) was administered intraperitoneally for 15 days, 2 days after intraperitoneal administration of Streptococcal preparation OK-432 to a patient of peritonitis carcinomatosa occurred eight months after second look operation, in which residual tumor could not be removed completely. The patient had been maintained by hemodialysis three times a week for over ten years. Combination chemotherapy using CDDP and Ifosfamide, or CDDP and THP-Adriamycin had not been effective to control rapidly increasing ascites. Negative cytological exam, was achieved on day 7 and ascites disappeared by day 15. No severe side effects including fluid retention were observed. Fever up was controllable by Indomethacin. Flow cytometric analysis revealed dominant (73%) CD4+, CD29+ helper inducer subset, while CD4+, CD45RA+ was 6%, in the lymphocytes in ascites on day 8. It was suggested that intraperitoneal administration of rIL-2 after OK-432 was safe and effective for peritonitis carcinomatosa with chronic renal failure.

Topics: Adenocarcinoma; Adult; Biological Products; Female; Humans; Immunization, Passive; Infusions, Parenteral; Interleukin-2; Kidney Failure, Chronic; Killer Cells, Lymphokine-Activated; Ovarian Neoplasms; Peritoneal Neoplasms; Picibanil

Combined effect of cis-DDP (II) (CDDP), a streptococcal preparation (OK-432) and systemic hyperthermia on ascites tumor in mice was studied. Tumor cells were of a syngeneic cloned cell line FMA3 which was derived from Furth's mastocytoma. When number of cells transplanted into the abdominal cavity was at 10(5), a single i.p. injection of CDDP at a dose of 4 mg/kg was effective to increase the mean survival time by a factor of 1.6. OK-432 given i.p. at a dose of 5 KE/kg on every two days between day 2 and day 10 after transplantation decreased the mean survival times. Even when it was used in combination with CDDP, enhancement of the effect of CDDP was not statistically significant. However, by the factorial analysis of the all data obtained in the experiments carried out with tumor cells of the number of 10(2), 10(3), 10(4) and 10(5), enhancement of the effect of CDDP by OK-432 was significant. Systemic hyperthermia of the core-body temperature of 40 degrees C was not effective when used alone, and did not enhance the effect of CDDP. However, combined use of it and OK-432 significantly enhanced the effect of CDDP.

Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Combined Modality Therapy; Hyperthermia, Induced; Male; Mast-Cell Sarcoma; Mice; Mice, Inbred Strains; Peritoneal Neoplasms; Picibanil

In this report the mechanism of therapeutic activity of OK-432 for the treatment of peritoneal carcinomatosis was investigated by correlating effector-cell augmentation with therapeutic activity in rats bearing MADB-106 carcinomatosis. Tumor cells were injected i.p. and the treatment with OK-432 was initiated 5 days later with 0.5, 1, 5 or 10 KE/animal of OK-432 injected i.p. semiweekly. Significant therapeutic activity was observed at all doses examined with greater prolongation of survival noted at the higher doses of OK-432. Animals treated with 0.5 KE/animal had a prolongation of the median survival time from 14 days for saline-treated animals to 17 days for the OK-432 treated animals (P less than 0.0008), while animals treated with higher doses had much longer periods of survival, some animals being tumor-free at 185 days. In the same studies, natural killer (NK) cell, lymphokine-activated killer cell, cytotoxic T lymphocyte, and macrophage tumoricidal/cytostatic activities were measured 7 days and 14 days following tumor injection (2 days and 9 days after initiation of immunotherapy). OK-432 had immunostimulatory activity in most of the assays of immune function examined and this correlated with host survival, including augmentation of peritoneal and peripheral blood cytotoxic T lymphocyte activity on day 14, peritoneal and alveolar macrophage activity on day 7 and day 14, as well as natural killer cell activity on day 14. These results suggest that the therapeutic doses are also immunomodulatory doses for the effector cells mentioned above. We suggest, therefore, that immunological monitoring may help to optimize treatment protocols for the treatment of peritoneal and perhaps pleural effusions with OK-432.

Topics: Adjuvants, Immunologic; Animals; Biological Products; Carcinoma; Cell Line; Cytotoxicity, Immunologic; Female; Killer Cells, Natural; Mammary Neoplasms, Experimental; Neoplasm Transplantation; Peritoneal Neoplasms; Picibanil; Rats; Rats, Inbred F344; T-Lymphocytes, Cytotoxic

Topics: Animals; Biological Products; Female; Immunotherapy; Neutrophils; Peritoneal Neoplasms; Picibanil; Rats; Rats, Inbred Strains; Tumor Cells, Cultured

OK-432, a compound composed of penicillin-G-treated, attenuated Streptococcus pyogenes of human origin, was administered by intratumoral injection (IT) to 15 of 49 patients with Stage III gastric carcinoma, at the time of preoperative endoscopic examination. The 5-year survival rate of patients given IT was 73.3%, whereas the rate was only 36.5% in those not given IT (P less than 0.05). A study of recurrent cases revealed a significantly low incidence of peritoneal recurrence in the group on OK-432 IT (P less than 0.01). In previous work, the authors noted a favorable prognosis of patients with Stage III gastric carcinoma and with a marked infiltration of Langerhans' cells (LC) in the tumor tissues. All of the 49 in the current study were thus examined immunohistochemically, using anti-S-100 protein antibody, the objective being to clarify the relationship between OK-432 IT and the density of LC. The density of LC among those given IT was significantly increased as compared with those not given IT (P less than 0.05). The results of this study suggest that OK-432 IT may lead to augmentation of the density of LC in tumor tissues and hence prevent peritoneal recurrences in patients with Stage III gastric carcinoma.

Topics: Adenocarcinoma; Biological Products; Drug Evaluation; Gastroscopy; Humans; Langerhans Cells; Neoplasm Proteins; Peritoneal Neoplasms; Picibanil; S100 Proteins; Stomach Neoplasms; Streptococcus pyogenes

Carcinomas produce large amounts of prostaglandin (PG) E2, which play an important role in suppression of non-specific cellular immune reaction in tumor-bearing individuals. PG synthesis inhibitor can restore the immune activity against tumors. The anti-tumor activity of indomethacin was investigated in CDF1 mice (BALB/c X DBA/2) implanted intraperitoneally with mouse colon adenocarcinoma 26 (5 X 10(5) or 2 X 10(5) cells) in a model study to prevent peritoneal recurrence after surgery for gastrointestinal cancers. Oral administration of indomethacin (0.002% water solution as drinking water) depressed and inhibited the disseminated tumor growth in the abdominal cavity, and prolonged the survival time, resulting in 30-50% cures of mice. The treatment combined with a small intraperitoneal dose of Picibanil (OK-432) (0.5 mg/kg twice weekly), which activates macrophages in the abdominal cavity, cured 90% of mice. An intraperitoneal dose of 16,16-dimethyl-PGE2 (5 micrograms/mouse, daily) reduced the anti-tumor activity of indomethacin. The results suggest that indomethacin treatment relieved the endogenous(tumor cell- and macrophage-produced) PGE2-mediated immunosuppression. It is postulated that PG-synthesis inhibitor in combination with chemotherapeutic agents, immunotherapeutic agents and low dose radiation, may provide a good therapeutic tool to prevent the development of peritoneal carcinomatosis, particularly in the cases having a small number of residual cancer cells or micrometastases in the abdominal cavity after surgery.

Topics: Adenocarcinoma; Animals; Anti-Inflammatory Agents, Non-Steroidal; Colonic Neoplasms; Dinoprostone; Drug Therapy, Combination; Immune Tolerance; Indomethacin; Mice; Mice, Inbred Strains; Neoplasm Recurrence, Local; Peritoneal Neoplasms; Peritonitis; Picibanil; Prostaglandins E

We examined whether OK-432, a streptococcal preparation, could induce tumor necrosis factor in cancer patients. OK-432 was administered at a dose of 100 KE intratumorally to 4 advanced gastric cancer patients and 10KE intracavitary to 8 patients with malignant pleuroperitoneal effusion. The cytostatic activity of the sera and malignant effusions was assayed by the growth inhibition of L929 cells. OK-432 induced significant cytostatic activity in the sera and malignant effusions. The activity was partially neutralized by the monoclonal antibody against human recombinant tumor necrosis factor. These data suggest that OK-432 induces tumor necrosis factor in the sera and malignant effusions of cancer patients.

Topics: Biological Products; Cytotoxicity, Immunologic; Glycoproteins; Humans; Neoplasms; Peritoneal Neoplasms; Picibanil; Pleural Neoplasms; Stomach Neoplasms; Tumor Necrosis Factor-alpha

Three cases of pseudomyxoma peritonei with ovarian neoplasma were treated by adjunctive immunotherapy with OK-432 after surgery. In 2 of the 3 cases, the periods of intramuscular injection of OK-432 were 11 and 16 months, respectively, and the 2 patients remain clinically free from evidence of disease, 7 and 6 years after surgery. The third patient is still undergoing treatment, with no evidence of recurrence at 4 months after surgery. These results, although for a small number of patients, clearly suggest that adjunctive immunotherapy with OK-432 may be suitable for treating pseudomyxoma peritonei of ovarian tumor origin.

Topics: Aged; Biological Products; Cystadenoma; Epithelium; Female; Humans; Immunotherapy; Middle Aged; Ovarian Neoplasms; Peritoneal Neoplasms; Picibanil; Skin Tests

The effect of intraperitoneal OK-432 administration and its mechanism of action were investigated using an experimental rat tumor. On day 4 or 6 of intraperitoneal inoculation of tumor cells, 50 Klinische Einheit (KE)/kg of OK-432 was intraperitoneally administered, and intraperitoneal exudate cells were microscopically examined daily. Distribution of peritoneal exudate cells: A marked increase in neutrophils was noted in ascites at 24 hours after intraperitoneal administration of OK-432, with macrophages and lymphocytes appearing later than neutrophils. A subsequent decrease in neutrophils was accompanied by a gradual increase in tumor cells. Findings of tumor cells: When OK-432 was intraperitoneally administered on day 4 of tumor inoculation, aggregation of neutrophils around tumor cells was observed on day 6, and rosette formations around tumor cells were noted on day 7 or 8. Subsequently tumor cells that formed the centers of the rosettes were destroyed and disappeared. These reactions were not observed when OK-432 was administered on day 6, nor were they observed in untreated cases. These results suggest that cytotoxic effects of intraperitoneally administered OK-432 were displayed mainly by rosette formation by neutrophilic cells, as far as this model was concerned.

Topics: Animals; Biological Products; Carcinoma; Disease Models, Animal; Female; Peritoneal Neoplasms; Picibanil; Rats; Rats, Inbred Strains

The effect of intraperitoneal (ip) OK-432 administration and its mechanism were investigated with experimental tumor of rats.. 4 week-old female SD rats (Slc/SD, closed colony). Tumor: An ascitic tumor, produced by intraperitoneal inoculation of strain cells. These have been established from MRMT-1, which originally was induced by 3-methyl cholanthrene administration. Experimental study: On day 4 or 6 of ip inoculation of 1 x 10(6) tumor cells, 50 KE/kg of OK-432 was administered intraperitoneally and cells were daily examined microscopically. Morphological changes around tumor cells were investigated with Papanicolaou-stained preparations. Following results were obtained: A marked increase in neutrophils was noted in ascitis at 24 hours after ip administration of OK-432; macrophages and lymphocytes appearing later than neutrophils. A subsequent decrease in neutrophils was accompanied by gradual increase in tumor cells. When OK-432 was administered intraperitoneally on day 4 of ip inoculation of tumor cells, aggregation of neutrophils around tumor cells was observed on day 6, and rosette formations around tumor cells with 76 to 10 neutrophils were noted on days 7 and 8. Subsequently tumor cells forming centers of rosettes were found to be destroyed and disappeared. On days 10 to 12, regrowth of tumor cells within incomplete rosette formation was found in ascites. The above reactions were not remarkable, when OK-432 was administered intraperitoneally on day 6 of ip inoculation of tumor cells, and were never observed in untreated cases. These results indicated that cytotoxic effects of ip administration of OK-432 were displayed mainly by rosette formation with neutrophilic cells.

Topics: Adjuvants, Immunologic; Animals; Biological Products; Female; Neoplasms, Experimental; Peritoneal Cavity; Peritoneal Neoplasms; Peritonitis; Picibanil; Rats