picibanil and Disease-Models--Animal

Topics: Animals; Colonic Neoplasms; Disease Models, Animal; Humans; Immunologic Surveillance; Immunotherapy; Interleukin-2; Killer Cells, Natural; Liver; Liver Neoplasms; Picibanil

Topics: Adjuvants, Immunologic; Alum Compounds; Animals; Asthma; Cell Differentiation; Disease Models, Animal; Humans; Immunoglobulin G; Immunomodulation; Immunotherapy; Interferon-gamma; Male; Mice; Mice, Inbred C57BL; Picibanil; Th1 Cells; Th2 Cells

Minimally invasive therapies, such as microwave ablation (MWA), are widely used for the treatment of solid tumors. Previous studies suggest that MWA is feasible for the treatment of small breast cancer, and thermal ablation may induce adaptive antitumor immunity. However, the induced immune responses are mostly weak, and the immunomodulation effects of MWA in breast cancer are unclear. Immunostimulant OK-432 can induce tumor-specific T-cell responses and may augment the immunity induced by MWA.. We treated 4T1 breast cancer bearing BALB/c mice with MWA, OK-432, MWA plus OK-432, or left without treatment. Survival time was evaluated with the Kaplan-Meyer method comparing survival curves by log-rank test. On day 25 after ablation, surviving mice received tumor rechallenge, and the rechallenged tumor volumes were calculated every 5 days. Immunohistochemistry and flow cytometry were used to evaluate the T-cell immune responses in ablated tissues and spleens. The tumor-specific immunity was assessed by enzyme-linked immunospot assays. Besides, the cytokine patterns were identified from enzyme-linked immunosorbent assay.. Microwave ablation plus OK-432 resulted in longer survival than single treatment and protect most surviving mice from tumor rechallenge. Both local and systemic T-cell responses were induced by MWA and were further enhanced by subsequent administration of OK-432. Moreover, the combination of MWA and OK-432 induced stronger tumor-specific immune responses than MWA alone. In addition, OK-432 and MWA synergistically promoted the production of Th1-type but not Th2-type cytokines, and polarized T-cell responses to Th1-dominant state.. The T-cell immune responses were activated by MWA in breast cancer. Furthermore, the combination of MWA and OK-432 induced Th1-type response and elicited specific antitumor immunity.

Topics: Animals; Cell Line, Tumor; Cell Polarity; Combined Modality Therapy; Cytokines; Disease Models, Animal; Female; Kaplan-Meier Estimate; Mammary Neoplasms, Animal; Mice, Inbred BALB C; Microwaves; Picibanil; Survival Analysis; T-Lymphocytes, Cytotoxic; Th1 Cells

This study aimed to assess the histopathological effect of OK-432 (Picibanil) on rabbit nasal turbinates.. A total of 21 rabbits were divided into 3 treatment groups and various parts of both nasal turbinates were injected with 0.5 ml OK-432, 0.2 ml OK-432 or 0.6 ml saline (control). Bilateral nasal turbinates were later excised and studied under light microscopy to assess any histopathological changes.. Animals in the 0.2 ml and 0.5 ml OK-432 groups exhibited mild ciliary loss, goblet cell loss and epithelial damage, and a marked increase in inflammatory cell infiltration, submucosal vascularisation and fibrosis. There was a significant difference in histopathological changes between the two OK-432 treated groups. In addition, each OK-432 treated group had significantly more inflammatory cell infiltration, increased submucosal vascularisation and fibrosis compared with controls.. The marked fibrosis observed in OK-432-injected turbinates may be responsible for a reduction in turbinate size.

Topics: Animals; Biopsy, Needle; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Administration Schedule; Immunohistochemistry; Injections, Intralesional; Male; Nasal Obstruction; Picibanil; Rabbits; Random Allocation; Sensitivity and Specificity; Turbinates

To evaluate survival and distant tumor growth after radiofrequency ablation (RFA) and local OK-432 injection at a single tumor site in a rabbit model with intra- and extrahepatic VX2 tumors and to examine the effect of this combination therapy, which we termed immuno-radiofrequency ablation (immunoRFA), on systemic antitumor immunity in a rechallenge test.. Our institutional animal care committee approved all experiments. VX2 tumors were implanted to three sites: two in the liver and one in the left ear. Rabbits were randomized into four groups of seven to receive control, RFA alone, OK-432 alone, and immunoRFA treatments at a single liver tumor at 1 week after implantation. Untreated liver and ear tumor volumes were measured after the treatment. As the rechallenge test, tumors were reimplanted into the right ear of rabbits, which survived the 35 weeks and were followed up without additional treatment. Statistical significance was examined by log-rank test for survival and Student's t test for tumor volume.. Survival was significantly prolonged in the immunoRFA group compared to the other three groups (P < 0.05). Untreated liver and ear tumor sizes became significantly smaller after immunoRFA compared to controls (P < 0.05). In the rechallenge test, the reimplanted tumors regressed without further therapy compared to the ear tumors of the control group (P < 0.05).. ImmunoRFA led to improved survival and suppression of distant untreated tumor growth. Decreases in size of the distant untreated tumors and reimplanted tumors suggested that systemic antitumor immunity was enhanced by immunoRFA.

Topics: Animals; Antineoplastic Agents; Catheter Ablation; Combined Modality Therapy; Disease Models, Animal; Ear Neoplasms; Female; Follow-Up Studies; Liver; Liver Neoplasms; Picibanil; Rabbits; Survival Analysis; Treatment Outcome

Animal-models are the basis of DC-based human immunotherapies. We describe the standardization of a canine-DC-generation protocol using different cytokines and characterize the quality and functional repertoire of the obtained canine-DCs. DCs were generated from healthy dog-PBMCs under serum-free and serum-containing conditions. DC-quality and -quantity was determined by FACS studying the expression-profiles of DC-/costimulatory- and maturation-antigens before/after culture with canine and human monoclonal-antibodies (cmabs/hmabs). Individual DCAgs-(DC-antigens)-expression-profiles were found before and after culture depending on the agents' mode-of-action. With at least one of three serum-free methods (Ca-Ionophore, Picibanil, Cytokines) sufficient DC-amounts were generated. So, canine-DCs can be regularly generated under serum-free conditions and hmabs additionally to cmabs qualify for staining/quantification of canine-cells/DCs. The canine-DCs were functional, shown by T-cell-activation, -proliferation and antigen-specific CTL-responses. In summary, successful, quantitative DC-generation is possible with serum-free methods. DC-based T-cell-vaccination-strategies evaluated for e.g. AML-patients can be tested in the dog and estimated in clinical studies for DC-vaccination-strategies.

Topics: Animals; Cell Culture Techniques; Cell Separation; Cells, Cultured; Culture Media, Serum-Free; Cytokines; Dendritic Cells; Disease Models, Animal; Dogs; Female; Flow Cytometry; Immunotherapy; Ionomycin; Male; Picibanil

There is no animal model of ganglion. We describe a simple and reproducible animal model of pseudocystic diseases. First, we experimented to establish a pseudocystic model. We used cylindrical glass implants (6 mm diameter, 30 mm long) to create fibrous capsules in rats. The implants were inserted in the subcutaneous tissue in the dorsum of rats. Sixty implants were carried out (two implants per rat). Twelve weeks after implantation, the glass implants were removed and 0.5 mL sodium hyaluronate solution was injected into each cavity. Next, we tested the model by histological examination after OK-432 administration. Microscopic examination revealed that the wall was composed of a layer of collagenous fibers similar to those noted in ganglia; the lumen was retained for 3 weeks. Histopathological changes after OK-432 administration showed nonspecific inflammatory response induced by OK-432, resulting in in vivo activation of many inflammatory cells and then fast and reliable closure of cavities. No harmful reactions to OK-432 were observed histopathologically. These data suggest that our experimental cyst is a suitable model for studying pseudocystic diseases. This model can be used for research evaluating safe drug doses, conducting therapeutic comparison of several agents, and histopathological time course studies of the affected tissues. OK-432 administration on this model showed the potential of one of the ideal agents to treat pseudocystic lesions like ganglion.

Topics: Animals; Antineoplastic Agents; Disease Models, Animal; Ganglion Cysts; Injections, Intralesional; Male; Picibanil; Rats; Rats, Wistar

Our aim was to investigate the effect of sclerosant agent OK-432 on tongue fibrosis and to determine whether the fibrosis formed by this substance increases with dose. Fifty Wistar albino rats were divided into three groups for the study. In the first group 0.2 ml OK-432, in the second group 0.5 ml OK-432, and in the third group physiological saline as the control substance was injected into the tongue of these rats. Subjects were sacrificed on the first day, first week, first month, third month and sixth month following the injection. Cross-sections of the tongues were stained with hematoxylin-eosin (HE) and Masson Tri-chrome. The degree of fibrosis was measured using ocular micrometry. A significant amount of fibrosis was observed in both the 0.2 ml (P = 0.020) and 0.5 ml (P = 0.003) OK-432 injection groups. OK-432 is a material that causes significant fibrosis in the muscle when compared to physiological saline. The degree of fibrosis in the tongue increases with dose.

Topics: Animals; Disease Models, Animal; Fibrosis; Injections; Male; Mouth Mucosa; Picibanil; Rats; Rats, Wistar; Sclerosing Solutions; Sleep Apnea, Obstructive; Snoring; Tongue Diseases

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

Cholangitis-induced liver damage was created in rats by intraductal injection of OK432, a lyophilized incubation mixture of group A Streptococcus pyogenes of human origin. Oral, low-dose methotrexate (MTX) was given to one group to study its protective effect on liver injury. The liver histology was studied and semiquantitatively graded. The OK432-induced changes were compared with and without MTX therapy. The results revealed statistically significant higher grades of portal inflammation and sinusoidal infiltration in rats treated with OK432 compared to saline-treated controls. There was significant improvement in liver changes in the group treated with MTX compared to the untreated group. It could be concluded that oral, low-dose, pulsed MTX therapy caused significant improvement in cholangitis-induced liver damage in rats.

Topics: Animals; Chi-Square Distribution; Cholangitis; Disease Models, Animal; Methotrexate; Picibanil; Rats; Statistics, Nonparametric

Priming with tumor antigens is one of the most important strategies in cancer immunotherapy. To enhance tumor antigenicity, OK-432, a streptococcal preparation, was coupled to squamous cell carcinoma (KLN-205) by means of a 0.2% glutaraldehyde method. The purpose of this study was to investigate whether OK-432-conjugated tumor vaccines could induce tumor-specific immunity. Our originally developed mouse tongue cancer model was used throughout this work for the analysis of antitumor effects. Prepared OK-432-conjugated KLN-205 vaccines were immunized 3 times to DBA/2 mice. The results showed that the KLN-205 vaccines induced cytolytic activity and strongly suppressed both KLN-205 tumor incidence and growth, and survival of the mice was improved. Moreover, the histological results showed that a greater number of lymphocytes had infiltrated around tumor cells by 24 hours after tumor inoculation in the vaccine group. These results suggest that immunizations with KLN-205 vaccines increase the antitumor effects against tongue cancer.

Topics: Animals; Antigens, Neoplasm; Antineoplastic Agents; Cancer Vaccines; Carcinoma, Squamous Cell; Disease Models, Animal; Female; Immunization; Lymphocytes; Mice; Mice, Inbred DBA; Picibanil; Survival Rate; Tongue Neoplasms; Vaccines, Conjugate

OK-432 is known to increase the host antitumor response. We previously reported that systemic administration of OK-432 (OK-Lipo) specifically induced hepatic lymphocytes in mice. Here we aimed to investigate the antitumor effect of OK-Lipo on hepatocellular carcinomas (HCC) in experimental rats.. Diethylnitrosamine was administered for 12 weeks to all rats (n = 36). Rats were divided into three groups of 12 rats each. One group was injected with OK-Lipo from week 5 (OK-5w group) and another from week 9 (OK-9w group). A control group was injected with saline from week 5 (Non-OK group). At week 13, five rats from each group were used for histological analysis and immunofluorescence assays (surface phenotypic and intracellular cytokine analysis of the mononuclear cells in the liver, spleen and peripheral blood). The remaining rats were observed for the remainder of their survival period.. The mean survival times of Non-OK, OK-5w, and OK-9w groups differed significantly (98.0 +/- 5.3 days, 116.0 +/- 5.8 days, and 106.0 +/- 5.4 days, respectively, P < 0.01). Histological examination revealed many apoptotic tumor cells, infiltration of lymphocytes and macrophages in the OK-5w group. The two-color immunofluorescence assay showed that the proportion of natural killer (NK) cells and IFN-gamma-producing cells in the liver were significantly higher in the OK-5w group.. These findings showed that systemic administration of OK-Lipo contributed to prolonging the survival of rats with HCC. OK-Lipo induced NK cells and IFN-gamma-producing cells specifically in the liver and these cells seemed to reduce hepatocarcinogenesis and tumor growth.

Topics: Animals; Carcinoma, Hepatocellular; Disease Models, Animal; Interferon-gamma; Killer Cells, Natural; Liver; Liver Neoplasms, Experimental; Lymphocyte Subsets; Male; Picibanil; Rats; Rats, Wistar; Survival Analysis

OK-432 has been used clinically as a biological response modifier for cancer therapy. We investigated here the protective effects of OK-432 against endotoxic shock and infectious death caused by Pseudomonas aeruginosa and Salmonella enteritidis in mice and proposed a possible mechanism. Pretreatment of OK-432 reduced the lethality of lipopolysaccharide (LPS)-induced endotoxic shock in D-(+)-galactosamine-sensitized C3H/HeN mice. OK-432 did not affect the TNFalpha production in blood, but it did decrease the susceptibility to TNFalpha. Furthermore, an acceleration of LPS clearance from blood was detected. The pretreatment of OK-432 also decreased the lethality of mice in bacterial infection caused by P. aeruginosa and S. enteritidis. The rapid decrease of the viable bacteria from the circulating blood and in spleen and liver in mice was observed in a manner similar to LPS clearance. These findings indicate that the protective effect of OK-432 against the endotoxemia and bacteremia may depend on an up-regulation of clearance of LPS and bacteria and the augmented resistance to TNFalpha.

Topics: Animals; Bacteremia; Colony Count, Microbial; Disease Models, Animal; Dose-Response Relationship, Immunologic; Endotoxemia; Female; Lipopolysaccharides; Male; Mice; Mice, Inbred C3H; Picibanil; Pseudomonas aeruginosa; Pseudomonas Infections; Salmonella enteritidis; Salmonella Infections; Shock, Septic; Tumor Necrosis Factor-alpha

Topics: 9,10-Dimethyl-1,2-benzanthracene; Angiogenesis Inhibitors; Animals; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Cyclohexanes; Disease Models, Animal; Female; Mammary Neoplasms, Experimental; Mice; Mice, Nude; O-(Chloroacetylcarbamoyl)fumagillol; Picibanil; Prognosis; Rats; Receptors, Estrogen; Risk Assessment; Sesquiterpenes; Tamoxifen; Tegafur; Treatment Failure; Uracil

We investigated whether the combination treatment of 15 cGy total body irradiation (TBI) and a streptococcal preparation, OK-432, synergistically suppresses spontaneous lung metastasis and augments phytohemagglutinin (PHA) and concanavalin A (Con A) responses of splenocytes in WHT/Ht mice. TBI with 15 cGy was carried out 20 days after subcutaneous injection of squamous cell carcinoma cells into a hind leg. Lung colony number was counted 40 days after tumor injection. For PHA and Con A responses, mice were killed 4 hr after 15 cGy TBI. The combination treatment of 15 cGy TBI and OK-432 was most effective when OK-432 was administered 2 days before 15 cGy TBI. The combination treatment decreased the lung colony number to 29.9% of the control number. OK-432 slightly increased the PHA and Con A responses, and 15 cGy TBI did not increase them. However, when these two were combined, the PHA and Con A responses were significantly increased to 393% and 278% of the control levels, respectively. It was suggested that TBI and OK-432 acted synergistically in suppressing the lung metastasis and mitogenic response of splenocytes.

Topics: Animals; Antineoplastic Agents; Carcinoma, Squamous Cell; Cells, Cultured; Combined Modality Therapy; Disease Models, Animal; Dose-Response Relationship, Radiation; Female; Growth Substances; Lung Neoplasms; Mice; Mice, Inbred Strains; Picibanil; Radiation Dosage; Spleen; Whole-Body Irradiation

A well-known metastic model of human oral cancer employs 9,10-dimethyl-1,2-benzanthracene (DMBA) to induce hamster cheek-pouch carcinoma. Streptococcal immunopotentiator OK432 was studied here for its inhibitory effect on lymph-node metastasis in that model. The intraperitoneal administration of OK432, after excision of cheek-pouch tumours induced by DMBA, resulted in a marked reduction in the incidence of cervical lymph-node metastasis to 7%, a significant decrease beneath the rates observed for control animals not receiving OK432 (40%). OK432 also caused an increased in serum levels of tumour necrosis factor-alpha and interleukin-6 in tumor-bearing hamsters. These results suggest that the immune response may play an important part in the antimetastatic effects of OK432.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Adjuvants, Immunologic; Animals; Antineoplastic Agents; Carcinogens; Carcinoma, Squamous Cell; Cheek; Cricetinae; Disease Models, Animal; Humans; Injections, Intraperitoneal; Interleukin-6; Lymphatic Metastasis; Male; Mesocricetus; Mouth Neoplasms; Picibanil; Tumor Necrosis Factor-alpha

A murine tumor model showing metastases to lymph nodes (LN) was established by intradermally implanting highly metastatic MM48 tumor cells (2 x 10(6)) in C3H/HeN mice. We were searching for the most effective immunochemotherapeutic modality to treat this metastatic tumor. The combination therapy with chemotherapeutics, granulocyte colony-stimulating factor (G-CSF) and OK-432 on Days 8-11 was found to be remarkably effective, making the solid tumor disappear in more than half of the treated mice, though all of them eventually died of LN metastasis, as all the control mice did. Then an attempt was made to cure the mice from such fatal metastatic tumors with combined immunochemotherapy prior to surgical resection on Day 14. The combination therapy with chemotherapeutics, G-CSF and OK-432 more strongly inhibited the metastases then, and more than 85% of the mice survived. When the survivors were rechallenged with MM48 tumor cells, all of them rejected and survived without recurrences and metastases, indicating the acquirement of specific immunity. It is expected that this preoperative immunochemotherapy may be clinically useful for the treatment of malignant neoplasms.

Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Disease Models, Animal; Female; Granulocyte Colony-Stimulating Factor; Immunotherapy; Lymphatic Metastasis; Mammary Neoplasms, Experimental; Mice; Mice, Inbred C3H; Picibanil

An experimental model for hepatic metastasis with a transplantation route of free-pedicled subcutaneous-embedded spleen was established in BALB/c mice. Colon-26 tumor cells to produce hepatic metastasis were inoculated into the spleen and the influence of surgical stress by means of a 20-min exposure of the abdominal cavity on the incidence of hepatic metastasis was examined. Hepatic metastasis was more promoted by the surgical stress in order when it was given on the same day, the 7th day and the 3rd day of the inoculation. Administration, without surgical stress, of ASGM 1, a specific inhibitor of the natural killer activity, also facilitated the hepatic disease. Administration of OK-432 prior to the surgical stress or ASGM 1 was at least partly effective for prevention of the hepatic metastasis and prolonged the survival of the inoculated mice. Preoperative immunotherapy utilizing OK-432 might be a possible means to prevent hepatic metastasis triggered in colorectal surgery for cancer.

Topics: Animals; Antibodies; Antineoplastic Agents; Colonic Neoplasms; Cytotoxicity, Immunologic; Disease Models, Animal; G(M1) Ganglioside; Killer Cells, Natural; Liver Neoplasms; Male; Mice; Mice, Inbred BALB C; Neoplasm Transplantation; Neoplastic Cells, Circulating; Picibanil; Stress, Physiological; Surgical Procedures, Operative

We have established a metastatic model of human gastric cancer using orthotopic transplantation of histologically intact tissue in nude mice, and have used this model to evaluate the effects of immunochemotherapy using OK-432, 5-fluorouracil (5-FU) and mitomycin C (MMC) against SC-I-NU, a human stomach cancer line. One-quarter or one-half maximum tolerated doses (MTDs) of 5-FU or MMC resulted in a significant reduction of stomach tumor growth, while liver metastases were not reduced, possibly due to suppression of natural killer (NK)-cell activity by both drugs. On the other hand, when combined with OK-432, half MTDs of 5-FU and MMC significantly reduced liver metastases, with synergistic reduction of stomach tumor growth, possibly reflecting a rescue of NK-cell activity by treatment with OK-432. This metastatic model of human stomach cancer shows that locally growing and metastatic tumors may have different chemosensitivities, and provides the opportunity to test both with various treatment regimens.

Topics: Adenocarcinoma; Animals; Antineoplastic Combined Chemotherapy Protocols; Cell Count; Combined Modality Therapy; Disease Models, Animal; Drug Screening Assays, Antitumor; Fluorouracil; Humans; Immunotherapy; Killer Cells, Natural; Liver Neoplasms, Experimental; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Mitomycin; Neoplasm Transplantation; Picibanil; Spleen; Stomach Neoplasms; Transplantation, Heterologous

We have reported that OK-432 (a streptococcal preparation) prevents the development of autoimmune kidney disease in MRL/Mp-lpr/lpr (MRL/lpr) mice and prolongs their survival time. In the present study, to clarify the mechanism of this action of OK-432, we examined whether the cyclooxygenase inhibitor indomethacin (IND) affects this inhibition by OK-432. It was reconfirmed that OK-432 prevented the development of autoimmune kidney disease and prolonged the survival time. This OK-432 effect was counteracted when IND was coadministered. Furthermore, OK-432 produced tumor necrosis factor (TNF)-alpha and prostaglandin (PG) E2 in the peritoneal fluids in this strain of mice. The coadministration of IND suppressed the PGE2 but not the TNF-alpha production. These results suggest the possibility that the inhibition of autoimmune kidney disease by OK-432 might be due to the induction of cyclooxygenase metabolites of arachidonic acid.

Topics: Animals; Antibodies, Antinuclear; Antigen-Antibody Complex; Autoimmune Diseases; Dinoprostone; Disease Models, Animal; Immunoglobulin M; Indomethacin; Kidney Diseases; Male; Mice; Mice, Inbred Strains; Picibanil; Tumor Necrosis Factor-alpha

The rabbit ovarian carcinoma model was prepared by injecting VX-2 carcinoma into the ovary and the effects of endogenous Tumor Necrosis Factor (TNF)-induction therapy in combination with chemotherapy were studied. In this model, carcinoma metastasizes easily to the abdominal cavity, lung and liver, and resists treatment. Endogenous TNF was induced by a series of injections of OK-432 0.3KE and OK-432 3KE at 3 hour intervals (OK-OK group), or 1 x 10(10) cells of Bordetella pertussis vaccine (BPV group). Another group were sequential given a series of injections of CDDP (2mg/kg) intraperitoneally and OK-432 intravenously (an OK-OK and CDDP group). Higher activity of endogenous TNF was induced by BPV in comparison with OK-OK plus OK-OK and CDDP. Obvious hemorrhagic necrosis was observed in the implanted ovary in the BPV group. Compared with the control group, pulmonary metastasis was seen in the OK-OK and OK-OK plus CDDP groups (partial remission). These results show that the endogenous TNF induction therapy could be expected to be an effective antitumor therapy for advanced ovarian cancer.

Topics: Animals; Carcinoma; Cisplatin; Combined Modality Therapy; Disease Models, Animal; Female; Neoplasm Metastasis; Ovarian Neoplasms; Pertussis Vaccine; Picibanil; Rabbits; Tumor Necrosis Factor-alpha

Topics: Animals; Autoimmune Diseases; Diabetes Mellitus, Type 1; Disease Models, Animal; Humans; Lymphocytic choriomeningitis virus; Picibanil

The relationship between host immune state and hepatic inflammation and infection pattern of the Duck hepatitis B virus (DHBV) was investigated by experimental transmission of DHBV into 98 Japanese 7-day-old ducklings that had been pretreated with immunoregulatory drugs including cyclophosphamide, OK 432, and a steroid hormone. Immunosuppressive treatment with cyclophosphamide revealed an extension of the viremic period associated with an absence of inflammatory changes in the liver. Although immunostimulating treatment with OK 432 showed a remarkable accumulation of inflammatory cells in the liver, the viremic period was not shortened. Treatment with a steroid used as a immunosuppressant did not suppress the hepatitis; moreover, it increased viral DNA replication and extended the viremic period. This phenomenon of viral replication seemed to be caused by the direct effects of the steroid. Alteration of DHBV infection by modifying the host immune state is quite similar to that of hepatitis B virus (HBV) in humans. In DHBV infection, the host immune state seemed to have a considerable role in determining the infection pattern and degree of hepatitis activity. DHBV may be a helpful model of HBV for studying host-viral interaction and the immunological mechanism of viral hepatitis.

Topics: Adjuvants, Immunologic; Animals; Carrier State; Cyclophosphamide; Disease Models, Animal; DNA-Directed DNA Polymerase; DNA, Viral; Ducks; Hepatitis B; Hepatitis B virus; Hepatitis, Viral, Animal; Hydrocortisone; Immunosuppressive Agents; Picibanil; Viremia; Virus Replication

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