picibanil and Kidney-Neoplasms

Cytokine treatment of renal cell carcinoma is described, focusing on interferons (IFN) and interleukin-2 (IL-2). Some cases with excellent responses are being reported, but long term follow-up results are rare. The results of monotherapy by cytokine are not satisfactory, so effective combination therapies with cytokines are awaited in future studies. Effects of the ongoing mono-therapy by cytokines are limited. For further development of the treatment, analyses of the complicated production system of cytokines and interactions are prerequisite.

Topics: Carcinoma, Renal Cell; Female; Humans; Interferon-alpha; Interleukin-2; Kidney Neoplasms; Male; Middle Aged; Picibanil

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 intracavitary injection of OK-432 (a streptococcal preparation) with subcutaneous priming has been shown to be an effective immunotherapy for patients with malignant effusion. We applied this treatment in a case of advanced renal cell carcinoma with massive ascites. The patient received 0.2 Klinishe Einheit (KE) OK-432 in the subcutaneous injection twice (day 1 and day 7) followed by 10KE OK-432 intra-abdominal administration (day 9). The treatment was performed safely without major side-effects except for transient pyrexia. A significant reduction of ascites was noted 1 month after the treatment without subsequent re-accumulation. Intracavitary injection of OK-432 with subcutaneous priming seems to be a simple, safe and effective treatment for ascites in advanced renal cell carcinoma.

Topics: Antineoplastic Agents; Ascites; Carcinoma, Renal Cell; Disease Progression; Humans; Injections; Kidney Neoplasms; Male; Middle Aged; Picibanil

A total of 12 patients with advanced renal cell carcinoma received interferon alpha (3 million units intramuscularly 6 times weekly) and OK-432 (5 KE (Klinische Einheit) intramuscularly twice weekly). Metastatic lesions appeared before operation in six patients and after operation in six patients. Among them 5 patients had received interferon therapy and this combination therapy was started after the judgment of progressive disease for interferon therapy. Eleven pulmonary and 5 bone metastases were evaluable. The median duration of the combination therapy was 89.3 weeks. There were 4 partial responses and no complete responses among the 12 patients, giving a response rate of 33.3%. The median duration of response was 25 months, with a range of 6 to 54 months. Responses were seen predominantly in patients in whom metastases appeared after operation (3 of 4 responders). However, regarding the individual organs, two complete and 2 partial responses were observed among 11 pulmonary metastases and 2 partial responses among 5 bone metastases. The survival period after discovery of the metastasis was 10 to 67 months and the 5-year survival rate was 70.5%. Almost all patients had fever and induration at the injection site. Other side effects included leukopenia, anorexia, and depression. This combination therapy is thought to be effective against bone or other organs metastasis resistant to interferon alone.

Topics: Aged; Bone Neoplasms; Carcinoma, Renal Cell; Female; Humans; Immunotherapy; Injections, Intramuscular; Interferon-alpha; Kidney Neoplasms; Lung Neoplasms; Male; Middle Aged; Picibanil

This study was undertaken to determine the production of tumor necrosis factor (TNF) and interferon-gamma (IFN-gamma) by biological response modifier (BRM) in patients with renal cell carcinoma (RCC). Peripheral blood mononuclear cells (PBMC), which were donated from thirteen patients with RCC and five healthy controls, were cultured with streptococcal preparation, OK432, and/or macrophage-colony stimulating factor (M-CSF), and the TNF levels and IFN-gamma levels in the supernatant were evaluated. TNF activities were assayed by cytotoxicity to L929 cells and IFN-gamma activities were measured by inhibition of the cytopathic effects of sindbis virus on FL cells. The highest levels of TNF in the supernatant were 235.4 +/- 96.0 U/ml/1 x 10(4) cells in patients with renal cell carcinoma and 251.6 +/- 71.8 U/ml/1 x 10(4) cells in healthy controls, which were noted at 12 hours of incubation with the concentration of OK432 adjusted to 0.05 KE/ml. There was no statistically significant difference between the TNF activities induced by in vitro culture of PBMC obtained from patients with renal cell carcinoma and those from healthy controls. The production of TNF by in vitro culture of PBMC with OK432 of 0.05 KE/ml was augmented by adding 100 U/ml M-CSF especially at 48 and 72 hours of incubation, whereas M-CSF alone did not stimulated TNF production. The medium levels of IFN-gamma in six different cultures of PBMC with 0.05 KE/ml OK432 at 12, 24 and 48 hours of incubation were 1.15 +/- 0.34 U/ml/l x 10(4) cells, 2.23 +/- 0.93 U/ml/l x 10(4) cells, and 7.83 +/- 4.00 U/ml/l x 10(4) cells, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Carcinoma, Renal Cell; Humans; Interferon-gamma; Kidney Neoplasms; Macrophage Colony-Stimulating Factor; Middle Aged; Picibanil; Tumor Cells, Cultured; Tumor Necrosis Factor-alpha

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

Synergistic effect of recombinant IFN-gamma (IFN-gamma) and OK-432, a streptococcal preparation, using chromium release assay was studied in vitro on killer cell induction. The target cells utilized for assay were a human leukemia cell line K562, a human renal carcinoma cell line KU-2, autologous normal kidney tissues and autologous renal cell carcinomas. Culture supernatant of peripheral blood lymphocytes (PBL) and OK-432 (designated as OK conditioned medium or OK-CM) demonstrated enhanced cytotoxicity of fresh PBL against these target cells. Killer cell activity against autologous cancer cells could be also induced from PBL of renal cell carcinoma patients. Pretreatment of PBL with IFN-gamma revealed synergistic effect of OK-CM on killer cell induction. OK-CM derived from patients was shown to contain IL-2 activity as well as high titer of interferon. Neutralizing monoclonal antibody against IFN-gamma and IL-2 receptor demonstrated reduction of cytotoxicity. These results suggested potential benefit of sequential use of IFN-gamma and OK-432 for the treatment of metastatic renal cell carcinoma.

Topics: Biological Products; Carcinoma, Renal Cell; Cytotoxicity, Immunologic; Humans; Immunotherapy; Interferon-gamma; Kidney Neoplasms; Picibanil; Tumor Cells, Cultured

In the present study we investigated the effect of OK-432, a streptococcus preparation, on the contact-mediated inhibition of human NK activity by primary cultures of monolayer cells. Either peripheral blood lymphocytes (PBL) or large granular lymphocytes (LGL) were incubated (2 x 10(6) cells/ml, total volume 2 ml) on confluent monolayer cells (uvea-derived fibroblasts, uvea-derived melanoma cells, or renal carcinoma cells) for 18 h in 24-well plates, washed twice, and tested for cytotoxicity against K562, a human myelogenous leukemia cell line, in a 4 h 51Cr-release assay. After contact with monolayer cells, NK activity of both PBL and LGL was significantly reduced. When these effector cells were preincubated with 0.1 U/ml of OK-432 for 18 h and then tested for the sensitivity to contact-mediated inhibition, the inhibition was significantly reduced. The pretreatment of monolayer cells with OK-432 or the addition of OK-432 into the coculture wells (of effector cells and monolayer cells) also significantly reduced the contact-mediated inhibition. Moreover, OK-432 (0.1 U/ml) reestablished the inhibited NK activity of PBL. These results suggest that OK-432 might enable NK cells to escape from the contact-mediated inhibition by monolayer cells and thus provide an additional potential mechanism for the observed clinical effectiveness of OK-432 reported by many groups.

Topics: Adenosine Triphosphate; Carcinoma, Renal Cell; Cell Communication; Cells, Cultured; Cytotoxicity, Immunologic; Fibroblasts; Humans; Immunologic Factors; Kidney Neoplasms; Killer Cells, Natural; Melanoma; Picibanil; Streptococcus pyogenes; Tumor Cells, Cultured; Uvea; Uveal Neoplasms

A first case of synchronous double cancers in the ovary and kidney is presented. The patient is a 37-year-old woman complaining of an abdominal mass. Histopathological findings showed a mucinous cystadenocarcinoma of the right ovary and a renal cell carcinoma, common type, clear cell subtype of the right kidney. A metastatic renal cell carcinoma was found on the pelvic peritoneum and characteristic renal cancer cells were identified in the ascitic fluid. (. ovarian cancer, stage Ia; renal cancer, stage IV) The patient received postoperative chemotherapy and, after recovery, was discharged in a healthy condition. Her 11-month postoperative evaluation revealed no evidence of disease.

Topics: Adenocarcinoma, Mucinous; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Renal Cell; Combined Modality Therapy; Cyclophosphamide; Doxorubicin; Drug Administration Schedule; Female; Fluorouracil; Humans; Kidney Neoplasms; Middle Aged; Neoplasms, Multiple Primary; Ovarian Neoplasms; Peptichemio; Picibanil; Postoperative Care

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Renal Cell; Humans; Interferon-gamma; Kidney Neoplasms; Lung Neoplasms; Male; Middle Aged; Picibanil; Remission Induction

A rare case of metastatic renal cell carcinoma which represented complete remission by chemotherapy and surgical treatment is presented. A 59-year-old female was admitted to our hospital because of general fatigue, weight loss and appetite loss. The diagnosis of right renal tumor metastasized to both lungs and extending into the inferior vena cava was made by radiographic findings. Because of very poor general condition the first choice of treatment was chemotherapy with cisdichlorodiamine platinum, adriamycin, cyclophosphamide, 1-(2-tetrahydrofuryl)-5-fluorouracil) (UFT), and OK432. Five months after the beginning of chemotherapy both lung coin lesions disappeared completely, and radical nephrectomy including venacavotomy and tumor thrombectomy was performed. At present, 6 months after the radical nephrectomy, she is free from the disease and complete remission has been obtained by oral administration of 400 mg/day UFT and 5.0 KE OK432 intracutaneous injection every week.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Renal Cell; Cisplatin; Combined Modality Therapy; Cyclophosphamide; Doxorubicin; Female; Humans; Kidney Neoplasms; Lung Neoplasms; Middle Aged; Nephrectomy; Picibanil; Remission Induction; Tegafur; Thrombosis; Uracil; Vena Cava, Inferior

The strong tumor-selective cytocidal action of tumor necrosis factor (TNF) has been observed in vitro and in vivo. Sato et al. have reported that it was possible to induce a primed state of TNF triggering by injection of purified protein derivative (PPD) even a long time after BCG sensitization, suggesting that this treatment could be applied to human patients. In the present study, we achieved a partial response of a metastatic lesion in a patient with renal cancer by the induction of endogenous TNF by PPD and OK-432 (a streptococcal preparation). This study suggested the possible application of this therapy to also patients with malignant tumor which are highly resistant to any conventional antitumor therapy.

Topics: Biological Products; Carcinoma, Renal Cell; Glycoproteins; Humans; Kidney Neoplasms; Lung Neoplasms; Male; Middle Aged; Picibanil; Tuberculin; Tumor Necrosis Factor-alpha

In 8 cases of operable renal cancer, selective intraarterial infusion of the streptococcal preparation, OK-432 was performed and its cytocidal effects on the surgical specimens, which were removed on the 8th day after infusion, were investigated histopathologically with immunological parameters of the peripheral blood. The histopathological study revealed a high grade of sinus histiocytosis of the renal pedicle lymph nodes, but the anti-tumor effect on renal tumors was not so marked in any of the 8 cases. OK-Ia-positive lymphoid cells of peripheral blood were increased significantly and Con-A stimulation index of blastogenesis was lowered without any change in the PHA stimulation index after the OK-432 infusion. No serious complications of the selective intraarterial infusion were experienced except for high fever (less than 38 degrees C). In conclusion, OK-432 selective intraarterial infusion was an effective method for improving regional and systemic immunoactivity, but the cytocidal effect against tumor cells could not be confirmed histopathologically.

Topics: Aged; Biological Products; Carcinoma, Renal Cell; Female; Humans; Infusions, Intra-Arterial; Kidney Neoplasms; Lymphocyte Activation; Lymphocytes; Male; Middle Aged; Picibanil

Renal cell carcinoma (RCC) is one of the most insensitive urologic tumors to either radiotherapy or anticancer chemotherapy. Recently, effectiveness of interferon (IFN) against RCC has been reported. However, because this effect is somewhat limited, a new modality of treatment is needed. We herein report our experience with IFN and OK-432, a streptococcal preparation for patients with advanced RCC. Twenty patients aged from 26 years to 75 years, with an average age of 52.3 years, were entered into this study. Intramuscular injection of human lymphoblastoid interferon (HLBI) at a dose of 3 X 10(6) units was given daily for between 4 and 76 weeks. Treatment with OK-432 then followed HLBI, unless the patient achieved CR or the status of the patient seriously deteriorated during the initial treatment with HLBI. OK-432 was given to 12 patients at a dose of 5KE (Klinische Einheit) 2 days a week for between 10 and 64 weeks. Effectiveness of HLBI therapy was 20% (CR 1 case, MR 3 cases, NC 11 cases, PD 5 cases). With adjuvant OK-432 therapy for patients whose disease proved to be resistant to HLBI, effectiveness was 25% (CR 1 case, MR 2 cases, NC 6 cases, PD 3 cases). The results obtained indicated that OK-432 following IFN is a potentially active antitumor regimen in patients with advanced RCC.

Topics: Adult; Aged; Biological Products; Carcinoma, Renal Cell; Drug Therapy, Combination; Humans; Interferon Type I; Kidney Neoplasms; Lung Neoplasms; Male; Middle Aged; Picibanil

Topics: Animals; Biological Products; Glycoproteins; Humans; Kidney Neoplasms; Lung Neoplasms; Male; Mice; Middle Aged; Nephrectomy; Picibanil; Tuberculin; Tumor Necrosis Factor-alpha

Topics: Antineoplastic Combined Chemotherapy Protocols; Biological Products; Carcinoma, Renal Cell; Humans; Kidney Neoplasms; Lung Neoplasms; Male; Medroxyprogesterone; Medroxyprogesterone Acetate; Middle Aged; Picibanil

In the use of hyperthermia treatment, it is apparent from the work of other investigators that only a proportion of large clinical neoplastic tumors of substantial size and deep location can be heated to adequate temperatures (over 42 degrees c). It is therefore of major significance that we have tested the concept that OK-432 can be used as an immunoheat potentiator. A ThermaTech 2000 was used as the radio-frequency generator at 13.56 MHz, including an ancillary computer in the thermometry unit. Minor response in advanced and metastatic tumors was observed in 3 of 3 evaluable patients using OK-432. With other anticancer drugs, no change was observed in 11 of 16 patients, and progressive disease in 5 of 16. However, OK-432 has severe side effects including chills & fever, therefore improved immunoheat potentiators are desirable.

Topics: Biological Products; Body Temperature; Carcinoma, Renal Cell; Colonic Neoplasms; Female; Humans; Hyperthermia, Induced; Infusions, Parenteral; Kidney Neoplasms; Male; Middle Aged; Picibanil; Rectal Neoplasms

A total of 24 patients with urothelial cancer were treated with a combination chemotherapy consisting of vincristine (1 mg, i.v., day 1), bleomycin (15 mg, or peplomycin, 10 mg, i.m. day 2), mitomycin-C (4 mg, i.v. day 3), tegafur (600-750 mg, p.o., every day) and OK-432 (2-4 KE, i.m., day 1, 3, 5). This one-week course was repeated for an average of 4.6 courses. Of these cases, 13 patients with early stage treated as adjuvant chemotherapy after radical operation showed strong suppressive effects against tumor recurrence or metastasis except 3 cases. However, in advanced cancer this regimen was less effective. Therefore, we modified this regimen: VCR 2mg and PEP, 10 mg on days 2, 4 and 6. This modified regimen was given to two patients and one showed partial response and I-A according to Karnofsky's criteria. Mild side effects such as slight leukopenia, fever up, gastrointestinal symptoms or alopecia were observed. These results suggest that this regimen could be used as an adjuvant chemotherapy after radical operation of urothelial malignancy for the purpose of protecting tumor recurrence or metastasis.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Combined Modality Therapy; Female; Humans; Kidney Neoplasms; Male; Middle Aged; Mitomycin; Mitomycins; Picibanil; Tegafur; Ureteral Neoplasms; Urinary Bladder Neoplasms; Urologic Neoplasms; Vincristine

Topics: Biological Products; Cell Line; Cytotoxicity, Immunologic; Humans; Immunotherapy; Interferon Inducers; Kidney Neoplasms; Killer Cells, Natural; Male; Picibanil; Prostatic Neoplasms