JaLCDOI 10.18926/AMO/32645
FullText URL fulltext.pdf
Author Orita, Kunzo| Fuchimoto, Sadanori| Kurimoto, Masashi| Ando, Shunsaku| Minowada, Jun|
Abstract <p>Synergistic enhancement of anti-tumor effects through the combined use of natural human interferon-alpha (nHuIFN-alpha) and natural human tumor necrosis factor-alpha (nHuTNF-alpha) enabled us to decrease the effective dose of each cytokine and consequently to reduce side effects. One hundred and twenty patients with advanced or recurrent solid cancer were entered in the trial from April 1985 to January 1988, of whom 112 patients were evaluable. A mixture of nHuINF-alpha and nHuTNF-alpha was injected intravenously as the maintenance dose 1 x 10(6)U or more/day for over 8 weeks. There was no response in 40 patients injected with the maintenance dose of 1 x 10(6)U/day, but of 72 patients receiving more than 2 x 10(6)U/day (10 micrograms of nHuIFN-alpha and 3 micrograms of nHuTNF-alpha), 4 had complete responses, 10 had partial responses, and 4 had minor responses. The overall response rate was 12.5% (14/112) and the rate was 19.5% in 72 patients with more than 2 x 10(6)U/day. Positive responses were as follows: hepatoma 3/8), renal cell cancer (4/11), breast cancer (4/17), ovarian cancer (1/2), malignant thymoma (1/1) and liposarcoma (1/1). Serious adverse effects like hypotension, oliguria and severe hepatobiliary toxicity were never experienced. The effective and adequate dose of the mixed preparation was considered 2 to 4 x 10(6)U/day/body.</p>
Keywords interferon-? tumor necrosis factor-? cancer combination therapy early phase ?
Amo Type Article
Published Date 1992-04
Publication Title Acta Medica Okayama
Volume volume46
Issue issue2
Publisher Okayama University Medical School
Start Page 103
End Page 112
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language 英語
File Version publisher
Refereed True
PubMed ID 1575056
Web of Sience KeyUT A1992HR48400007
JaLCDOI 10.18926/AMO/32403
FullText URL fulltext.pdf
Author Fuchimoto, Sadanori|
Abstract <p>Active enhancement was induced in inbred rats with cardiac allografts using semisoluble antigens. The optimal time of antigen pretreatment and optimal dose of semisoluble antigens were examined. The presence of serum blocking factors in the sera of rats having had allografts for a long time was examined with a macrophage migration inhibition test and lymphocyte microcytotoxicity assay. Since the blocking factors of macrophage migration inhibition were increasing on the 7th day, that day was determined to be the optimal time of antigen pretreatment. The mean survival time (MST) of cardiac allografts in untreated rats was 17.2 +/- 7.5 days. Semisoluble antigens were administered at 2 mg/kg body weight 7 days before the graft, 4 mg/kg 7 days before the graft and 2 mg/kg divided over three days, 15, 8 and 1 day before the graft, and the MSTs of cardiac allografts of rats receiving these treatments were 71.2 +/- 39.9, 62.6 +/- 42.2 and 79.3 +/- 31.0 days, respectively. The MST in each group of the treated rats was significantly longer than that of the control group (p less than 0.01). Rejection of the allograft, however, was accelerated in a group treated with 8 mg/kg 7 days before the graft (MST: 8.4 +/- 3.2 days). Serum blocking factors were detected in the sera of approximately half of the rats having cardiac allografts which survived a long time.</p>
Keywords active enhancement optimal time of antigen pretreatment serum blocking factor rat cardiac allograft
Amo Type Article
Published Date 1983-12
Publication Title Acta Medica Okayama
Volume volume37
Issue issue6
Publisher Okayama University Medical School
Start Page 471
End Page 481
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language 英語
File Version publisher
Refereed True
PubMed ID 6198870
Web of Sience KeyUT A1983RW62800003
JaLCDOI 10.18926/AMO/32201
FullText URL fulltext.pdf
Author Shiiki, Sigeo| Fuchimoto, Sadanori| Iwagaki, Hiromi| Akazai, Yoshihiro| Matsubara, Nagahide| Watanabe, Tetsuya| Orita, Kunzo|
Abstract <p>We investigated the antitumor activities of 5-fluorouracil (5-FU), 5'-deoxy-5-fluorouridine (5'-DFUR), 1-hexylcarbamoyl-5-fluorouracil (HCFU) and 1-(tetrahydro-2-furanyl)-5-fluorouracil (FT-207) in combination with hyperthermia in vitro. The antitumor effect of 5-FU (10(-4) M) was slightly enhanced by combination with hyperthermia (42 degrees C) for 2h, and the effect was determined to be additive. Synergistic enhancement of antitumor activity was obtained by the concurrent use of hyperthermia (42 degrees C, 2h) and 5'-DFUR (10(-4) M) or HCFU (10(-5) M). However, the antitumor effect of FT-207 (10(-4) M) in combination with hyperthermia was comparable that of hyperthermia alone. The synergistic enhancement of antitumor activity was not obtained for all drugs when the cells were preheated at 42 degrees C for 2h. On the other hand, when cells were pretreated with drugs before heat exposure, weak interactions were obtained after 5-FU and 5'-DFUR treatment, and a synergistic interaction was obtained after HCFU treatment. It is speculated that the metabolites of 5'-DFUR and HCFU enhance the cytotoxicity of 5-FU, or might change the threshold concentration for a cytotoxic effect of 5-FU in cancer cells.</p>
Keywords hyperthermia 5-fluorouridine 5'-deoxy-5-fluorouridine 1-hexylcarbomoyl-5-fluorouracil FT-207
Amo Type Article
Published Date 1991-10
Publication Title Acta Medica Okayama
Volume volume45
Issue issue5
Publisher Okayama University Medical School
Start Page 339
End Page 345
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language 英語
File Version publisher
Refereed True
PubMed ID 1836706
Web of Sience KeyUT A1991GN53800008
JaLCDOI 10.18926/AMO/31939
FullText URL fulltext.pdf
Author Sakagami, Kenichi| Takeuchi, Hitoshi| Tsuboi, Katsutoshi| Matsumoto, Takamasa| Tanaka, Kohtaro| Ohsaki, Toshihide| Horimi, Tadashi| Fuchimoto, Sadanori| Orita, Kunzo|
Abstract <p>The survival rate of 19 patients who underwent living-related kidney transplantation after donor-specific blood transfusions (DST) was compared with that of 32 historical controls receiving transplants without DST. The graft survival rate of the DST group was 82% after two and three years. The graft survival rate of the DST group was significantly better than the 53% rate after two years obtained with the 32 historical controls (p less than 0.05). We tested sera from 16 DST-treated recipients to study the beneficial effect of DST on kidney allograft survival using the mixed lymphocyte culture (MLC) serum inhibition test. The results demonstrated that MLC inhibitory factors were induced in the serum of the recipient after completion of DST. This inhibition of MLC was observed by treatment of responder lymphocytes with serum obtained three weeks after DST plus rabbit complement. The inhibitory effect was also specific for responder cells in anti-donor MLC. Regarding the correlation with rejection episodes, these MLC inhibitory factors were often observed in the non-rejection group (p less than 0.05). The data suggest that such factors may be anti-idiotypic antibodies and be associated with prolonged graft survival.</p>
Keywords kidney transplantation donor-specific blood transfusion (DST) MLC inhibitory factors anti-idiotypic antibody.
Amo Type Article
Published Date 1986-02
Publication Title Acta Medica Okayama
Volume volume40
Issue issue1
Publisher Okayama University Medical School
Start Page 39
End Page 43
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language 英語
File Version publisher
Refereed True
PubMed ID 2938423
Web of Sience KeyUT A1986A190200006
JaLCDOI 10.18926/AMO/31030
FullText URL fulltext.pdf
Author Iwagaki, Hiromi| Fuchimoto, Sadanori| Orita, Kunzo|
Abstract <p>The same chemotherapeutic agents were tested against fresh surgical explants of solid tumors obtained from 50 patients using the in vivo subrenal capsule (SRC) assay and the in vitro succinate dehydrogenase inhibition (SDI) test in comparison. Control growth adequate to meet evaluable assay criteria was obtained in 36 of the 50 tumors tested in the SRC assay (72.0%). In the SDI test, 46 of 50 tumors were evaluable (92.0%). Correlations between the two test systems were dependent upon the activity criteria established for each system. With activity criteria set at a change of less than or equal to -2.0 in the drug sensitivity score for the SRC assay and greater than or equal to 50.0% inhibition of succinate dehydrogenase activity for the SDI test, 12.5% of the drugs tested were active in the SRC assay and 22.3% were active in the SDI test. Correlations of tumor response between the two test systems were 31.7% for sensitivity (13/41) and 95.1% for resistance (98/103). In spite of the fundamental difference between the SRC assay and SDI test, meaningful correlations between the test results and clinical tumor responses in both test systems were obtained. This fact suggests that the two methods are complementary to each other.</p>
Keywords drug sensitivity test subrenal capsule assay succinate dehydrogenase inhibition test
Amo Type Article
Published Date 1988-06
Publication Title Acta Medica Okayama
Volume volume42
Issue issue3
Publisher Okayama University Medical School
Start Page 121
End Page 127
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language 英語
File Version publisher
Refereed True
PubMed ID 3400481
Web of Sience KeyUT A1988P034000001
JaLCDOI 10.18926/AMO/30895
FullText URL fulltext.pdf
Author Nishiyama, Yoshitaka| Fuchimoto, Sadanori| Orita, Kunzo|
Abstract <p>We investigated the antitumor effect of purified natural human tumor necrosis factor-beta (nHuTNF-beta) produced by human acute lymphoblastic leukemia BALL-1 cells stimulated with HVJ on pulmonary metastatic tumors of Lewis lung carcinoma (3LL) transplanted into BDF1 mice. nHuTNF-beta showed antiproliferative effects on metastatic tumors in a dose-dependent manner when administered daily for 10 days by the intravenous route. Histological examination of the tumors treated with nHuTNF-beta revealed that the tumor size and number of metastases were much reduced. Lytic cellular changes, including cytoplasmic vacuolation, loosening of the intercellular junction and both cytoplasmic and nuclear swelling, were found, but tumor necrosis was not. These findings indicate a therapeutic effect of Grade IIa according to the histological criteria of Shimosato and Ohboshi. In addition, synergistic augmentation of the antiproliferative effects of nHuTNF-beta by natural murine interferon-alpha/beta (nMu-IFN-alpha/beta) or recombinant murine interferon-gamma (rMuIFN-gamma) was recognized by median effect plot analysis. The results suggested that nHuTNF-beta may well deserve clinical trial as a new immunotherapeutical agent for human cancer.</p>
Keywords tumor necrosis factor interferon Lewis lung carcinoma synergistic potentiation antitumor effect
Amo Type Article
Published Date 1989-02
Publication Title Acta Medica Okayama
Volume volume43
Issue issue1
Publisher Okayama University Medical School
Start Page 17
End Page 27
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language 英語
File Version publisher
Refereed True
PubMed ID 2470233
Web of Sience KeyUT A1989T938500003
JaLCDOI 10.18926/AMO/30883
FullText URL fulltext.pdf
Author Tomochika, Hiroshi| Gouchi, Akira| Okanobu, Kouji| Sasaki, Akinori| Fuchimoto, Sadanori| Orita, Kunzo|
Abstract <p>In order to improve the postoperative prognosis of gastric cancer patients we have performed preoperative endoscopic intratumoral administration of various biological response modifiers. In the present study we have investigated the kinetics and the immune response augmenting effect of intratumorally injected PSK, a protein-bound polysaccharide preparation, by immunohistochemical methods using anti-PSK antibody and various other antibodies. PSK-containing cells were located in the tumor tissues and follicular marginal zones of regional lymph nodes. Intratumorally administered PSK appeared to be phagocytized by the histiocytes and to cause them to become antigen-presenting cells. These cells may play a major role in augmenting immune responses in gastric cancer patients.</p>
Keywords PSK immunohistochemistry gastric cancer
Amo Type Article
Published Date 1989-10
Publication Title Acta Medica Okayama
Volume volume43
Issue issue5
Publisher Okayama University Medical School
Start Page 289
End Page 297
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language 英語
File Version publisher
Refereed True
PubMed ID 2610006
Web of Sience KeyUT A1989CA06200005
Author Orita, Kunzo| Sakagami, Ken-ichi| Fuchimoto, Sadanori| Arima, Toshihisa| Tanaka, Sanae|
Published Date 1977-06
Publication Title Acta Medica Okayama
Volume volume31
Issue issue3
Content Type Journal Article
JaLCDOI 10.18926/AMO/30452
FullText URL fulltext.pdf
Author Moreira, Luis Fernando| Iwagaki, Hiromi| Watanabe, Kazuhiko| Yoshino, Tadashi| Fuchimoto, Sadanori| Orita, Kunzo|
Abstract <p>A rare gastrointestinal tract neoplasm, primary non-Hodgkin's B-cell lymphoma in a 39-year-old, asymptomatic woman is described. The tumor was originally localized in the rectum without evidence of any other lymphoma-involved organ and treated by curative surgical procedure associated with postoperative chemotherapy.</p>
Keywords primary lymphoma rectum surgical treatment
Amo Type Article
Published Date 1990-10
Publication Title Acta Medica Okayama
Volume volume44
Issue issue5
Publisher Okayama University Medical School
Start Page 279
End Page 282
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language 英語
File Version publisher
Refereed True
PubMed ID 2260500
Web of Sience KeyUT A1990EG00700008
JaLCDOI 10.18926/AMO/30436
FullText URL fulltext.pdf
Author Sasaki, Akinori| Fuchimoto, Sadanori| Orita, Kunzo|
Abstract <p>Meth A-fibrosarcoma bearing BALB/c mice were subjected to selected splenic irradiation (2.0-4.0 Gy) on days 7 and 14 of tumor growth. Tumor growth was recorded by serial measurement. Irradiation given on day 7 caused regression of tumor, but irradiation given on day 14 did not show tumor regression. Antitumor activity in the Winn assay was detected in spleen cells 3 days after irradiation, but was not detected 7 days after. The cell surface phenotypes were analyzed on days 3, 7 and 14 of splenic irradiation using monoclonal antibodies (anti-Thy1.2 antibody, anti-Lyt1 antibody, anti-Lyt2 antibody, anti-L3T4 antibody) by flow cytometry. Thy 1.2, Lyt1, and L3T4 cells were increased on day 3 of splenic irradiation, but were not on days 7 and 14. Lyt2-cells did not show increase on days 3, 7 and 14. It was possibly suggested that selected splenic irradiation induced tumor regression was caused by the ability of irradiation to preferentially eliminate suppressor T cells, thereby allowing effector T-cells to become relatively dominant.</p>
Keywords selected splenic irradiation suppressor T-cell flow cytometry
Amo Type Article
Published Date 1990-12
Publication Title Acta Medica Okayama
Volume volume44
Issue issue6
Publisher Okayama University Medical School
Start Page 309
End Page 314
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language 英語
File Version publisher
Refereed True
PubMed ID 2150147
Web of Sience KeyUT A1990EP70700004
JaLCDOI 10.18926/AMO/30421
FullText URL fulltext.pdf
Author Sanada, Eiji| Fuchimoto, Sadanori| Orita, Kunzo|
Abstract <p>To prevent the development of hepatic metastases after surgery for colorectal cancer, it is important to inhibit the growth of any micrometastases which occur during the operation. We used a hepatic metastasis model in mice to investigate the effects of combination therapy with natural human tumor necrosis factor-alpha (nHuTNF-alpha) and natural murine interferon-alpha/beta (nMuIFN-alpha/beta). Decreased formation of hepatic metastases by murine colon-26 carcinoma was recognized following a single injection of nHuTNF-alpha, nMuIFN-alpha/beta, or both. These inhibitory effects were synergistic. NK activity was also measured, because notaral lerller cells not only have an anti-tumor effect but are also a representative of the host immune system. Both nHuTNF-alpha and nMuIFN-alpha/beta were able to activate NK cells, and the combination of the cytokines more significantly augmented NK activity. The in vivo elevation of NK activity induced by nHuTNF-alpha, nMuIFN-alpha/beta, or their combination may be one of the mechanisms of their antiproliferative effect on experimental hepatic metastases of murine colon-26 carcinoma.</p>
Keywords nHuTNF-? nMuIFN-?/? antiproliferative effect hepatic metastasis NK acitivity
Amo Type Article
Published Date 1990-08
Publication Title Acta Medica Okayama
Volume volume44
Issue issue4
Publisher Okayama University Medical School
Start Page 217
End Page 222
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language 英語
File Version publisher
Refereed True
PubMed ID 2244476
Web of Sience KeyUT A1990DX04500006