picibanil and Neoplasm-Metastasis

Primary retroperitoneal tumors are reported to account for 0.2% of all malignancies. Furthermore, 10-20% of all primary retroperitoneal tumors are liposarcomas. Up to 1989, 213 cases of retroperitoneal liposarcoma have been reported in the Japanese literature to our knowledge. Mixed type liposarcomas were rare, and composed 13.8% of all retroperitoneal liposarcomas in this series. We described here a case of retroperitoneal mixed type liposarcoma. A 50-year-old man was admitted to our department with a mass in the left abdomen. Computed tomography and aortography revealed a huge and hypovascular tumor in the retroperitoneal cavity, not containing fat tissue. It was diagnosed as a retroperitoneal tumor and treated surgically. The tumor and the left kidney were encapsulated and could be removed en bloc. The size and weight of the tumor were 28 x 18 x 12 cm and 3,100 g, respectively. Histological examination of the mass proved it to be a mixed type liposarcoma. He was administered OK-432 as adjuvant therapy. After 11 months, bone metastasis to the vertebra appeared. Moreover, lung metastasis also occurred and he died of the disease 15 months after the operation.

Topics: Combined Modality Therapy; Humans; Liposarcoma; Male; Middle Aged; Neoplasm Metastasis; Picibanil; Retroperitoneal Neoplasms; Tomography, X-Ray Computed; Urography

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

The usefulness of UFTMO therapy (combined chemotherapy with UFT, MMC and OK-432) performed in 40 cases of recurring or advanced cancer of the digestive organs was investigated. According the response criteria by Koyama et al., of 40 eligible cases, the treatment was judged effective in 13, 2 CR and 11 PR cases with a response rate of 32.5%, while of the 35 complete cases, 2 CR and 9 PR cases made for 11 effective cases and a response rate of 31.4%. Side effects were observed in 58.3% of the 36 evaluated cases; of the subjective and objective side effects, however, none were serious enough to require cessation of administration, while stopping administration in the cases of abnormal laboratory findings resulted in rapid recovery. UFTMO therapy, therefore, is considered to be one of the beneficial treatments for recurring or advanced cancer of the digestive organs.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Digestive System Neoplasms; Drug Evaluation; Female; Humans; Male; Middle Aged; Mitomycin; Mitomycins; Multicenter Studies as Topic; Neoplasm Metastasis; Neoplasm Recurrence, Local; Picibanil; Remission Induction; Tegafur; Uracil

Topics: Administration, Oral; Adolescent; Adult; Aged; Antineoplastic Agents; Carcinoma, Adenoid Cystic; Carcinoma, Squamous Cell; Clinical Trials as Topic; Drug Therapy, Combination; Female; Fluorouracil; Head and Neck Neoplasms; Humans; Male; Mouth Neoplasms; Nasopharyngeal Neoplasms; Neoplasm Metastasis; Neoplasm Recurrence, Local; Picibanil; Proteoglycans; Tegafur

Malignant pleural effusion is a common and devastating complication of metastatic breast cancer. This occurs in about 30% of patients with metastatic breast cancer during the clinical course, and chemical pleurodesis is sometimes performed to relieve dyspnea. However, the long-term outcome of pleurodesis and factors affecting successful pleurodesis have not been clarified.. The aim of this analysis is to evaluate the long-term outcome of pleurodesis and to identify risk factors associated with success.. Data on 75 patients who had undergone chemical pleurodesis with OK-432 for pleural effusion due to metastatic breast cancer were reviewed retrospectively. The primary outcomes were success rate and pleural progression-free survival (PPFS) rate.. The median duration of follow-up was 134 days (range 8-975 days). During this period, 22 patients re-accumulated pleural fluid. The overall success rate was 70.5%. The 4-, 8- and 12-week PPFS rates were 88.0, 84.0 and 78.7% respectively. Multivariate analysis identified three unfavorable factors that were independently associated with unsuccessful pleurodesis, including estrogen-receptor negative status, a 24-h drainage volume of more than 100 mL before extubation and NSAID use. The PPFS rate at median follow-up was 93.5% in the low-risk group (n = 41, 0 or 1 unfavorable factor) and 55.1% in the high-risk group (n = 34, 2 or 3 unfavorable factors). The difference between the PPFS curves of the two risk groups was statistically significant (P < 0.001).. Pleurodesis for metastatic breast cancer was efficacious in controlling malignant pleural effusion. Our simple new risk model warrants further studies.

Topics: Adult; Aged; Antineoplastic Agents; Breast Neoplasms; Disease-Free Survival; Female; Humans; Middle Aged; Neoplasm Metastasis; Picibanil; Pleural Effusion, Malignant; Pleurodesis; Retrospective Studies; Survival Rate; Treatment Outcome

Many authors have reported that oral melanoma patients showed much worse prognosis than those with cutaneous melanoma. We investigated treatment method and prognosis of patients with oral malignant melanoma.. Twenty-one patients with oral melanoma treated at our hospital were investigated, with special reference to the influence of preoperative surgical procedures such as biopsy, incision, or tooth extraction on the prognosis.. All patients underwent surgery followed by immuno-chemotherapy with dimethyl triazeno imidazole carboxamide (DTIC), ninustine hydrochloride (ACNU), vincristine (VCR), and biologic response modifier OK-432. Local control was obtained in 20 of 21 patients. Lymph node metastasis appeared in 13 patients, but neck failure was not detected in any patients. Distant metastasis occurred in 9 patients in spite of loco-regional control. Five-year survival rate of 12 patients with no preoperative surgical procedure was 91.7%, while that of the 9 patients who had undergone surgical procedures before treatment was 25.9% (P < .05).. Oral melanoma patients can obtain a prognosis as good as that for cutaneous melanoma patients, when the above-mentioned therapy is used without any preoperative surgical procedures.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Biopsy; Contraindications; Dacarbazine; Female; Humans; Immunotherapy; Kaplan-Meier Estimate; Male; Melanoma; Middle Aged; Mouth Neoplasms; Neoplasm Metastasis; Nimustine; Picibanil; Prognosis; Risk Factors; Tooth Extraction; Vincristine

Dendritic cells (DCs) have been shown to be potent in inducing cytotoxic T cell (CTL) response leading to the efficient anti-tumor effect in active immunotherapy. Myeloid DCs are conventionally generated from human peripheral blood monocytes in the presence of interleukin (IL)-4 and granulocyte/macrophage colony-stimulating factor (GM-CSF). Streptococcal preparation OK-432, which is known to be a multiple cytokine inducer, has been extensively studied as to its maturation effects on immature DCs using an in vitro culture system. The purpose of this study was to examine whether it could be possible to generate mature DCs directly from peripheral monocytes using OK-432. We specifically focused on the possibility that recombinant cytokines, which are considered to be essential for in vitro DC generation, could be substituted by OK-432. Human peripheral monocytes, which were obtained from patients with advanced cancer, were cultured with IL-4 and OK-432 for 7 days. Cultured cells were compared with DCs generated in the presence of IL-4 and GM-CSF with or without OK-432 with regard to the surface phenotype as well as the antigen-presenting capacity. As a result, the culture of monocytes in the presence of IL-4 followed by the addition of OK-432 on day 4 (IL-4/OK-DC) induced cells with a fully mature DC phenotype. Functional assays also demonstrated that IL-4/OK-DCs had a strong antigen-presenting capacity determined by their enhanced antigen-specific CTL response and exerted a Th1-type T cell response which is critical for the induction of anti-tumor response. In conclusion, human peripheral blood monocytes cultured in the presence of IL-4 and OK-432 without exogenous GM-CSF demonstrated a fully mature DC phenotype and strong antigen-presenting capacity. This one-step culture protocol allows us to generate fully mature DCs directly from monocytes in 7 days and thus, this protocol can be applicable for DC-based anti-tumor immunotherapy.

Topics: Antigen-Presenting Cells; Cell Culture Techniques; Dendritic Cells; Flow Cytometry; Humans; Interleukin-4; Lymphocyte Culture Test, Mixed; Monocytes; Neoplasm Metastasis; Picibanil

To investigate the histological effect of intranodal injection of the streptococcal preparation OK-432, we performed intranodal injection in 4 patients with cervical lymph node (CLN) metastases of malignant head and neck tumors (squamous cell carcinoma (SCC) of the oropharynx, SCC of the parotid gland, malignant lymphoma, and rhabdomyosarcoma of the nasal cavity). An initial dose of 5 klinische Einheit (KE) and a maintenance dose of 10 KE of OK-432 were administered into each metastatic or residually involved CLN twice a week. The total dose of OK-432 ranged from 105 KE to 395 KE and the number of administrations ranged from 11 to 40. Post treatment histological examination of excised tissue specimens revealed no tumor cells; there was only fibrosis and inflammatory cell infiltration. These findings suggest that intranodal injection of OK-432 can be utilized for treatment of relatively small CLN metastases of malignant head and neck tumors.

Topics: Aged; Antineoplastic Agents; Carcinoma, Squamous Cell; Head and Neck Neoplasms; Humans; Lymphoma; Male; Middle Aged; Neoplasm Metastasis; Picibanil; Retrospective Studies; Rhabdomyosarcoma

Intrasplenic administration of 1 x 10(6) C-1300 murine neuroblastoma cells induced spleen tumor in 78.6% of mice and liver metastasis in 64.3%. When mice were pretreated with carrageenan, an antimacrophage agent, the incidence of spleen and liver tumors in this system was lower, possibly due to the rebound increase in macrophage activity following the disappearance of the carrageenan effect. Continuous daily intraabdominal injection of 1 KE of OK-432 streptococcus preparation markedly reduced the appearance of liver metastasis (P less than 0.01), whereas the spleen mass was not reduced to such an extent. However, the survival rate of the OK-432-treated group did not differ greatly from that of the nontreated group. These results demonstrate the usefulness of the model of liver metastasis induced by intrasplenic administration of tumor cells and the effectiveness of OK-432 against liver metastasis formation.

Topics: Animals; Carrageenan; Immunity, Cellular; Immunotherapy; Liver Neoplasms; Macrophages; Male; Mice; Mice, Inbred A; Neoplasm Metastasis; Neuroblastoma; Picibanil; Spleen; Survival Analysis

In the early period following radical hepatectomy for hepatoma, recurrences in the remaining liver are frequently found. In regenerating liver, implantation and growth of tumour cells released into the portal system during surgical treatment might be promoted. We examined the relationship between liver regeneration and the formation of metastases following hepatic resection. Intraportal injections of rat ascites containing hepatoma AH130 cells at a concentration of 1 x 10(5) cells 0.2 ml-1 were made at various periods following two thirds liver resection in rats. Tumour cell injections immediately at 24 h after surgery resulted in an increased number of hepatic metastases compared with control animals. Tumour cell injections 2 weeks after hepatectomy, however, had no significant difference in effect compared with control rats. In contrast, tumour cells injected immediately after removal of half of the caudate lobe resulted in the same number of metastases as control animals. These results demonstrate that the number of artificially induced hepatic metastases was increased during an initial period of active liver regeneration and was proportional to the volume of hepatectomy. The effect of 5-fluorouracil (5FU) or mitomycin C (MMC) as inhibitors of hepatic regeneration on liver metastasis after hepatectomy was studied. The administration of 5FU (20 mg kg-1) or MMC (0.2 mg kg-1) immediately, 24 and 48 h after hepatectomy resulted in a marked reduction in metastatic lesions. The administration of 5FU caused delays in weight gain and decreases in the wet weight of remaining liver, while MMC had no effect on either. Accordingly, results of 5FU administration may be due to inhibitory effects on liver regeneration whilst that of MMC administration may be due to cytocidal antitumour effect. The effect of OK-432 as an immunoactivator on the implantation and growth of tumour cells in regenerating liver was also studied. Pretreatment with OK-432, 0.5 mg intraperitoneally on 7 consecutive days, had no effect on hepatic metastases. The pathophysiology of liver regeneration may enhance hematogenous hepatic metastasis and release of tumour cells during surgical manipulation may represent an important cause of recurrence following hepatic resection.

Topics: Animals; Fluorouracil; Liver; Liver Neoplasms; Liver Neoplasms, Experimental; Liver Regeneration; Mitomycin; Neoplasm Metastasis; Picibanil; Rats; Rats, Inbred Strains

The effect of the streptococcal preparation OK-432, which is one of the biological response modifiers, was examined in BALB/c mice using a transplantable murine renal cell carcinoma (Renca) of spontaneous origin, and an analysis of effector cells was performed. The tumor grew progressively and metastasized consistently to the abdominal lymph nodes and then to distant organs following the inoculation of Renca cells in the left renal subcapsular site in BALB/c mice, and the survival time of the mice was under 42 days. In this tumor model, i.p. administration of OK-432 after tumor inoculation significantly extended the survival time and significantly inhibited the formation of the inoculated tumor itself. Removal of the left kidney on the 7th day after tumor inoculation neither extended the survival time nor augmented the effect of OK-432. Splenic cells obtained on the 7th day after tumor inoculation from Renca-bearing mice treated with OK-432 were capable of lysing syngeneic Renca cells, NK-sensitive allogenic YAC-1 cells, and LAK-sensitive EL-4 cells in a 4-hour 51Cr-release assay in vitro. Those obtained from healthy mice treated with OK-432 also showed cytotoxic activity against Renca cells. The cytotoxicity of splenic cells from Renca-bearing mice treated with OK-432 was lost almost completely for both Renca and YAC-1 cells after in vitro treatment with anti-asialo GM1 antibody, and was partially lost after in vitro treatment with anti-Thy-1,2 antibody. Additionally, in vivo i.p. administration of anti-asialo GM1 antibody significantly counteracted the effect of OK-432 on survival. These findings demonstrated that Renca cells were NK-sensitive and that the i.p. administration of OK-432 was beneficial for the prevention of the spontaneous metastasis of Renca carcinoma. As the effectors, NK cells played a dominant role and activated T cells were also involved.

Topics: Animals; Carcinoma, Renal Cell; Female; G(M1) Ganglioside; Glycosphingolipids; Injections, Intraperitoneal; Kidney Neoplasms; Mice; Mice, Inbred BALB C; Neoplasm Metastasis; Neoplasm Transplantation; Picibanil

A comparative clinical study was conducted with an addition of vitamin A added to the auxiliary chemotherapies after surgical operation of gastric cancer. The OK-432 + MMC + Tegafur therapy (hereafter referred to as Group A) and the OK-432 + MMC + Tegafur + vitamin A therapy (Group B) were administered. The results were as follows. 1) The survival rate was slightly higher in Group B, although there was no significant difference between the two. 2) As to the rate of recurrence, it was significantly lower in Group B (p less than 0.05). The results above have suggested that additional vitamin A to the auxiliary chemotherapies after operation of gastric cancer can possibly be lower the recurrence rate, contributing to the prolongation of life.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Female; Gastrectomy; Humans; Lymphatic Metastasis; Male; Middle Aged; Mitomycin; Mitomycins; Neoplasm Metastasis; Picibanil; Postoperative Care; Stomach Neoplasms; Survival Rate; Tegafur; Vitamin A

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: Administration, Oral; Aged; Aged, 80 and over; Biological Products; Combined Modality Therapy; Female; Humans; Immunization, Passive; Male; Middle Aged; Neoplasm Metastasis; Neoplasms; Picibanil; Pilot Projects

Administration of several biological response modifiers (BRMs) to mice strongly augmented natural killer (NK) activity of leukocytes isolated from the liver. This augmentation of NK activity was induced by two synthetic molecules (MVE-2 and poly ICLC), by two BRMs of bacterial origin (formalin-fixed Propionibacterium acnes: P. acnes and a streptococcal cell wall preparation designated OK-432), as well as a single injection of human recombinant interleukin-2 (hrIL 2). All of these BRMs augmented NK activity in the liver to a greater degree than in the spleen. In addition, adherent leukocytes (greater than 90% macrophages) isolated from the liver following P. acnes administration also exhibited augmented macrophage-mediated cytotoxicity. This cytotoxicity was characterized as macrophage mediated and distinguished from NK activity, on the basis of adherence purification, kinetics of cytotoxicity, and target cell selectivity. The results demonstrate that a variety of BRMs induce augmented natural immunity in the liver and suggest that such organ-associated immune responses may play an important role in the antimetastatic effects of BRMs.

Topics: Adjuvants, Immunologic; Animals; Carboxymethylcellulose Sodium; Cytotoxicity, Immunologic; Female; Humans; Interleukin-2; Killer Cells, Natural; Liver; Macrophages; Mice; Mice, Inbred C57BL; Neoplasm Metastasis; Neoplasms; Picibanil; Poly I-C; Polylysine; Propionibacterium acnes; Pyran Copolymer; Recombinant Proteins; Spleen

A 60-year old woman with metastatic malignant melanoma who was well responded to a combination chemotherapy including DTIC was reported. She was noted a lentigo in the left first toe and histological examination revealed malignant melanoma in October 1978. Amputation of the left lower leg and dissection of the left inguinal lymph nodes had been done. OK-432 was injected as postoperative immunotherapy. She was readmitted to our hospital with the symptoms of pain and numbness of the left arm. Physical examination revealed a palpable mass in the left supraclavicular region. Incisional biopsy of the supraclavicular mass revealed metastatic malignant melanoma. She received a combination of 100mg DTIC i.v. for 5 days, 100 mg ACNU i.v. for one day and 1 mg VCR i.v. for one day (DAV chemotherapy) postoperatively. Subcutaneous injection of OK-432 with the dose of 5 KE per week was continued. Major side effects of DAV chemotherapy were nausea and transient leukocytopenia. No serious side effects were observed. On completion of the first course of DAV chemotherapy, abnormal shadow of the left apex was completely disappeared and on completion of the third course of DAV chemotherapy, high density area was markedly decreased in the cervical CT. She gained symptomatic reliefs and was discharged in August 1983. The combination chemotherapy including DTIC appeared to be effective in the treatment of metastatic malignant melanoma.

Topics: Antineoplastic Combined Chemotherapy Protocols; Dacarbazine; Drug Administration Schedule; Female; Humans; Melanoma; Middle Aged; Neoplasm Metastasis; Nimustine; Nitrosourea Compounds; Picibanil; Vincristine

Thirteen patients with malignant brain tumors, 12 anaplastic gliomas and one metastatic tumor, received repeated intratumoral injections of an immunopotentiator, Picibanil, prepared from streptococcus pyogenes. All patients tolerated this therapy; morbidity rates were acceptable. Significant tumor regression was noted on computerized tomography scanning for 6 of 12 patients for whom scanning was performed. Histologic examination of the post-therapy specimens obtained from 8 patients revealed that inflammatory reactions were evoked in all of the tumors, although the extent of inflammatory changes varied from patient to patient and mostly was localized to an area surrounding the intratumoral tubes.

Topics: Adjuvants, Immunologic; Adult; Aged; Biological Products; Brain Neoplasms; Female; Glioma; Humans; Injections; Male; Middle Aged; Neoplasm Metastasis; Picibanil; Streptococcus pyogenes; Tomography, X-Ray Computed