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Biomedical subjects

M Fukumoto

Publications and source records attributed to M Fukumoto.

At least 181 records · Page 10Linked to original sources
PubMed1992

Experimental chemotherapy for xenograft cell lines of human bile duct and gall bladder cancers in nude mice.

Most biliary tract cancers are advanced and inoperable when first diagnosed. Even if surgery can be performed, the postsurgical prognosis of these diseases is poor. In the present study, we investigated effective chemotherapies for a human bile duct cancer xenograft cell line (undifferentiated carcinoma, BDC-SN) and a gall bladder cancer xenograft cell line (well-differentiated adenocarcinoma, GBC-GN), which were transplanted into nude mice. Eight anticancer agents (CDDP, 5-FU, VDS, MMC, ADR, EPIR, CQ, and VP-16) and their various combinations were evaluated at 2-4 times the clinical dose. When used singly, CDDP, 5-FU, and VDS were effective against BDC-SN, and only CDDP was effective against GBC-GN. Among the various 2-agent combinations, CDDP + 5-FU was the most effective against both BDC-SN and GBC-GN. However, 3-agent combinations consisting of CDDP + 5-FU + another agent were less effective than the CDDP + 5-FU double regimen and caused significant loss of weight as well as high mortality. These results suggest that CDDP + 5-FU may be the most useful regimen against biliary tract cancers in clinical application.

Adenocarcinoma↗
PubMed1992

Usefulness of preoperative low dose cisplatin treatment for advanced esophageal cancer.

In order to decrease the perioperative complications by preoperative cisplatin chemotherapy, the preoperative single administration of cisplatin (30 mg/m2) was performed weekly from one to six times in 36 consecutive patients with esophageal cancer classified as higher than Stage II. The survival curve of 17 patients in Stage III was significantly better (P < 0.05) than that of patients who had been treated without preoperative cisplatin treatment. In 3 of the 12 patients who had locally invasive cancer, either the main tumors or the metastatic lymph nodes, which had invaded the trachea or the left main bronchus, sufficiently receded, so that a curative esophagectomy became possible; 2 of them have survived over 33 months while 1 died of pneumonia 33 months after surgery. The number of perioperative complications was minimal, and thus, we consider that the postoperative use of cisplatin and fluorouracil is indicated in patients in whom a histological response is noted in the resected specimens.

Aged↗
PubMed1992

Comparative effects of a recombinant and a mutein type of granulocyte colony stimulating factor on the growth of Meth-A fibrosarcoma with 5-fluorouracil chemotherapy.

The present study was designed to evaluate the effects of a recombinant human G-CSF (rhG-CSF) and a mutein G-CSF (KW-2228) on leucopenia and tumor growth in mice treated with 5-fluorouracil (5-FU). In normal mice, the number of leucocytes (white blood cell, WBC) reached the peak 12 hours after a single injection of either type of G-CSF and decreased to the normal level after 24 hours. Daily administration induced a continuous increase in the WBC count, however, administrations at intervals did not. Meth-A fibrosarcoma was subcutaneously inoculated into the backs of syngeneic BALB/c mice. The mice were treated with 5-FU alone or with G-CSFs. Chemotherapy with 5-FU alone resulted in leucopenia and an insignificant inhibition of tumor growth. The conjunctive administration of G-CSFs with 5-FU resulted in a significantly augmented inhibition of tumour growth, and leukopenia was not seen. This augmenting effect was more prominent with KW-2228. These results suggest that in 5-FU chemotherapy G-CSFs may be beneficial in restoring the number of leucocytes from leucopenic state and in augmenting the tumor inhibitory effect. Furthermore, KW-2228 may be more beneficial than the natural type rhG-CSF.

Amino Acid Sequence↗
PubMed1992

A comparative study on immunosuppressive effects of cyclosporin A and FK 506 on peripheral blood lymphocytes in dogs.

Immunosuppressive effects of cyclosporin A (CsA) and FK 506 (FK) on peripheral blood lymphocytes were studied in dogs in respect to mixed lymphocyte reaction, proliferative responses to recombinant interleukin-2 (rIL-2), phytohemagglutinin (PHA) and concanavalin-A (Con-A); phenotypes of OKIa1, CD3, CD8 and surface IgM; cytotoxic activity against xenogeneic tumor cells. CsA (2.0 or 5.0 mg/kg, intravenously) or FK (0.16 mg/kg, intramuscularly) was given to mongrel dogs every morning for serial 21 days. The blood concentrations of CsA, measured as trough levels by fluorescence polarization method, ranged from 37 to 350 ng/ml in dogs administered at 2.0 mg/kg and from 170 to 894 ng/ml in dogs administered at 5.0 mg/kg during treatment, respectively. In dogs treated with FK at a dose of 0.16 mg/kg, the drug concentrations in the plasma during treatment ranged from 0.16 to 1.8 ng/ml. Mixed lymphocyte reaction and proliferative responses to rIL-2, PHA and Con-A, which were declined by CsA, were not affected by FK. In contrast, the proportion of OKIa1+ cells was not affected by CsA, whereas FK decreased the proportion of OKIa1+ cells progressively during the course of treatment. Cytotoxic activity was suppressed by both CsA and FK. These results possibly indicate that CsA and FK exert their immunosuppressive effects via different mechanisms.

Animals↗
PubMed1992

IL-1 production as a regulator of G-CSF and IL-6 production in CSF-producing cell lines.

We previously demonstrated that colony stimulating factor (CSF)-producing cell lines co-produce interleukin-1 (IL-1) and IL-6 in addition to CSFs. In the present study, we examined the role of IL-1 production in three human tumour cell lines producing granulocyte (G)-CSF, IL-1 and IL-6. Addition of anti-human IL-1 alpha antiserum to the culture caused a 90-62% reduction of G-CSF and a 85-44% reduction of IL-6 production, respectively, as evaluated by enzyme immunoassay in all three cell lines. The decrease of G-CSF and IL-6 production by the anti-IL-1 alpha antiserum was also confirmed at the level of mRNA expression. The anti-IL-1 alpha antiserum did not affect the growth of these cell lines. Excess recombinant IL-1 alpha exogenously added to the culture enhanced G-CSF and IL-6 production in all three cell lines. However, IL-1 alpha had little effect on the growth of these three cell lines. Neither anti-IL-6 nor anti-G-CSF antibodies affected the production of the other cytokines. These results indicate that IL-1 alpha regulates G-CSF and IL-6 production in these tumour cell lines, and suggest that the IL-1 production plays an important role in CSF-producing tumours.

Cell Division↗
PubMed1992

A comparative study of the antitumor activities of 5'-deoxy-5-fluorouridine and its prodrug trimethoxybenzoyl-5'-deoxy-5-fluorocytidine (Ro09-1390) on human digestive organ cancer xenograft lines transplanted into nude mice.

5'-Deoxy-5-fluorouridine (5'-DFUR) is one of the oral fluoropyrimidines widely used in the treatment of gastric, colorectal and breast cancers in Japan. 5'-DFUR is converted to 5-fluorouracil by pyrimidine nucleoside phosphorylase in the tumor. 5'-DFUR has toxic effects on the intestine and may cause severe diarrhea. Trimethoxybenzoyl-5'deoxy-5-fluorocytidine (Ro09-1390) is a prodrug of 5'-DFUR, which was developed to reduce the intestinal toxicity of 5'-DFUR. The present study was designed to assess the antitumor activity and spectrum of Ro09-1390, and to compare its efficacy with that of 5'-DFUR. Six digestive organ cancer xenograft lines (two gastric, one esophageal, one colorectal, one gall bladder and one bile duct cancers) were s.c. transplanted into nude mice. The agents were orally administered daily for 14 days at doses of 0.08-0.64 mmol/kg (1-8 times the maximal clinical dose of 5'-DFUR). Both 5'-DFUR and Ro09-1390 significantly inhibited the growth of two gastric cancer lines, and the IC50's for Ro09-1390 in both lines were lower than the respective values for 5'-DFUR. The esophageal, colorectal, gall bladder and bile duct cancer lines, however, were resistant to both agents. 5'-DFUR at 0.64 mmol/kg significantly inhibited the growth of these cancers, but with high mortality, and most mice receiving this dose died within 14 days after the start of therapy, suffering from severe diarrhea and body weight loss. Ro09-1390 at the same dose resulted in low mortality, but evidenced similarly low antitumor activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Carcinosarcoma of the prostate.

A very rare case of carcinosarcoma of the prostate is reported. The patient was a 77-year-old man in whom both primary and metastatic tumors presented the pathology of carcinosarcoma of the prostate. The carcinosarcoma was resistant to anti-androgen therapy, and the patient showed low level of serum prostatic acid phosphatase and was free from bony metastases despite multiple metastases to the lung, liver, pancreas, para-aortic lymph nodes, spleen and penis. The sarcomatous component consisted of chondrosarcoma and fibrosarcoma, both of which were positive for vimentin. The carcinomatous component was positive for both keratin and prostatic acid phosphatase.

Acid Phosphatase↗
PubMed1992

Correlation of basic fibroblast growth factor expression levels with the degree of malignancy and vascularity in human gliomas.

Basic fibroblast growth factor (FGF) is a mitogen, a differentiation factor for neuroectoderm-derived cells, and a potent angiogenic factor. The authors have previously demonstrated that the messenger ribonucleic acid of basic FGF is expressed in more than 90% of human gliomas. In the present study, they examined the expression of basic FGF in human glioma tissues using immunohistochemical techniques with a mouse monoclonal antibody against human basic FGF. They also correlated the basic FGF level with the histological grades of malignancy assessed by the number of nucleolar organizer regions (NOR's). Basic FGF was detected in 18 of 19 gliomas, whereas it was undetectable in two normal brains. The expression level of basic FGF peptide increased proportionally with the degree of malignancy. There was also a tendency for the number of NOR's in glioma cells to increase in glioma samples with a high level of basic FGF expression. Furthermore, most of the cases with increased vascularity demonstrated on cerebral angiograms showed a relatively high level of basic FGF expression of tumor cells and a large number of NOR's in endothelial cells in tumor tissues. These results suggest that basic FGF is actually produced in most gliomas and is involved in tumorigenesis and malignant progression as an autocrine growth factor. Moreover, basic FGF may play an important role in tumor neovascularization as a paracrine angiogenic factor.

Animals↗
PubMed1992

c-kit gene expression in CD7-positive acute lymphoblastic leukemia: close correlation with expression of myeloid-associated antigen CD13.

Expression of human c-kit proto-oncogene and interleukin-7 receptor (IL-7R) in acute lymphoblastic leukemia (ALL) cells expressing CD7 was examined by Northern-blot analysis and reversed transcription polymerase chain reaction (RT-PCR) assay in relation to the phenotypes. Leukemic cells from four out of 12 CD7+ ALL patients, all of which fulfilled the criteria of ALL in the FAB classification, expressed c-kit genes. Surface CD3 (sCD3) was absent in all of these cases, while cytoplasmic CD3 (cCD3) was found in the two sCD3- cases. CD3 epsilon transcripts were detected in one of the sCD3- cCD3- cases. IL-7R genes were transcribed in the three cases with c-kit gene expression. In addition, there was a good correlation between c-kit gene expression and myeloid associated antigen CD13 positivity of the leukemic cells. None of the patients with c-kit gene expression had mediastinal tumor. Our results show that leukemic cells in a proportion of CD7+ ALL express receptors for cytokines that are secreted by bone marrow stromal cells. Ligands for c-kit genes and IL-7 could play an important role for the regulation of proliferation and differentiation of T-cell progenitors in bone marrow.

Antigens, CD↗
PubMed1992

Acquisition of growth autonomy and tumorigenicity by an interleukin 6-dependent human myeloma cell line transfected with interleukin 6 cDNA.

In human multiple myeloma, an autocrine growth mechanism through interleukin 6 (IL-6) has been advocated. However, growth of myeloma cells in vitro is poor except for established cell lines, and IL-6 autocrine growth is quite rare in myeloma cell lines. In the present study, we devised a model of IL-6 autocrine growth in vitro by transfecting IL-6 cDNA into a human myeloma cell line that had a proliferative response to IL-6 but did not produce IL-6. After IL-6 transfection, the cells proliferated in culture media without IL-6, and their growth rate was elevated at higher cell densities. IL-6 was detected by enzyme-linked immunosorbent assay in the culture media of the transfectants. IL-6 mRNA was distinctly expressed in these cells when analyzed by Northern blotting. The growth of the transfectants was definitely inhibited by anti-IL-6 or anti-IL-6 receptor monoclonal antibodies. Furthermore, the transfectants were successfully transplanted to nude mice. These results indicate that the myeloma cells obtained growth autonomy in vitro through IL-6 and tumorigenicity in vivo, after IL-6 transfection.

Animals↗
PubMed1992

[Effects of steroid therapy in IgA nephropathy].

In order to estimate the effects of corticosteroid therapy in IgA nephropathy cases with daily urinary protein excretion of 1.0 g/day or more. 26 patients (8 men and 18 women, aged 32.6 +/- 14.0 years old) were subjected to this study. The results obtained were as follows: Urinary protein excretion after 1 year from the beginning of steroid therapy (1.56 +/- 1.14 g/day) was significantly (p less than 0.05) lower than that at the beginning of the therapy (4.61 +/- 6.01 g/day). In serum creatinine levels, there was no statistically significant difference with them between at the beginning (1.15 +/- 0.48 mg/dl) of steroid therapy and at the time of 1 year after (1.05 +/- 0.34 mg/dl) the therapy. As for the outcome at the end of this study setting (mean follow-up duration: 3.7 +/- 2.6 years), complete remission was attained in 7 cases, improvement in 5 cases, unchanged condition in 11 cases, increased urinary protein excretion in 2 cases and aggravated renal function in 1 case. In clinical findings at the renal biopsy, duration of the disease (3.4 +/- 1.6 months) in complete remission cases before biopsy was significantly (p less than 0.01) shorter than that in unchanged cases (65.0 +/- 40.0 months). In histological findings, rate of global sclerosing glomeruli (2.6 +/- 4.6%) in complete remission cases was significantly (p less than 0.05) lower than that (24.6 +/- 23.1%) in unchanged cases. These results suggest that steroid therapy in IgA nephropathy with persistent proteinuria of 1.0 g/day or more is beneficial, especially in cases that are in early stage of the disease with lower rate of global sclerosing glomeruli.

Adolescent↗
PubMed1991

Enhanced expression of interleukin-6 in primary human renal cell carcinomas.

We have demonstrated interleukin-6 (IL-6) production by human renal carcinoma cells. The IL-6 gene expression was detected by Northern blot analysis in 22 of 43 primary renal cell carcinoma tissues and in five of seven renal cell carcinoma cell lines. Immunohistochemical analysis confirmed the expression of IL-6 by the tumor cells. Patients with a high-level expression of IL-6 had significantly greater incidences of lymph node metastasis and a larger increase in serum C-reactive protein than those without it. We have also probed for the presence of IL-6 receptor by Northern blot analysis; we detected this receptor in 11 of the 43 primary renal cell carcinoma tissues but in none of the seven renal cell carcinoma cell lines. However, by use of the complementary DNA-polymerase chain reaction, the IL-6 receptor transcript was detected in all specimens, including the seven cell lines. No expression of the interleukin-3 (IL-3) gene was identified in any of the 43 primary renal cell tumors. These data provide evidence that IL-6 and its receptor may play a role in promoting the transformation and/or proliferation of renal cell carcinomas as well as in teh development of symptoms.

Adult↗
PubMed1991

Analyses of T-cell differentiation from hemopoietic stem cells in the G0 phase by an in vitro method.

Using differential radiation sensitivity of components of mouse embryonal thymus, an in vitro method for studying T-cell differentiation from hemopoietic stem cells (HSCs) in the G0 phase was established. Intrathymic T-cell precursors present in embryonal thymus were found to be quite radioresistant (up to 20 Gy), and consequently 25-Gy-irradiated embryonal thymic lobes were used. Thymic lobes (25-Gy irradiated) taken from mouse fetuses (gestation day 15) were placed in Millipore-HA culture plates supported on squares of gelatin foam sponge in 24-well culture plates in which neonatal thymus stromal cells were cultured. HSCs (10(5) cells per well) in the G0 phase were added to these thymic lobes and cocultured at 37 degrees C in a 5% CO2/95% air incubator. Half the culture medium was changed every week. After 3 weeks, a large number of colonies had formed. Immunohistochemical studies and fluorescence-activated cell sorter analyses revealed that the colonizing cells regularly develop and exhibit surface markers characteristic of T cells (Thy-1, IL-2R, L3T4, Lyt-2, etc.). In situ hybridization analyses revealed that mRNA expression for T-cell receptor (TCR) beta chains occurred within colonizing cells. Using a monoclonal antibody (F23.1), expression of TCR beta-chain variable domain (V beta 8) on the surface of these developing T cells was demonstrated. These cells responded to interleukin 2 and/or anti-CD3 monoclonal antibody, indicating functional T cells. This method will be useful in studying T-cell differentiation pathways from pluripotent HSCs and in clarifying the mechanisms involved in negative and positive selection of T cells within the thymus.

Animals↗
PubMed1991

Inhibition of cell growth and tumorigenesis of human glioblastoma cells by a neutralizing antibody against human basic fibroblast growth factor.

We report here that a neutralizing mouse monoclonal antibody against basic FGF inhibited both anchorage-dependent and anchorage-independent growth of U-87MG and T98G human glioblastoma cells and HeLa cells, all of which express both the basic FGF and the FGF receptor genes. In addition, the subcutaneous administration of this antibody significantly suppressed the tumor development of these tumor cells in nude mice. Therefore, basic FGF plays an important role in neoplastic growth of these cells. The neutralization of basic FGF will be effective in controlling the growth of tumors, such as glioblastoma and other cancer cells which bear basic FGF and FGF receptors.

Animals↗
PubMed1991

Gene expression of fibroblast growth factor receptors in the tissues of human gliomas and meningiomas.

Northern blot analysis showed transcripts of two types of the fibroblast growth factor (FGF) receptor genes, flg and bek, in almost all the tissues samples of 18 human gliomas and 22 human meningiomas, which produced abundant basic and/or acidic FGF. From immunohistochemistry, FGF receptors were expressed in the tumor cells of a glioma and a meningioma. RNA expression of these FGF receptors was also detectable in normal human brains and normal bovine meninges. The expression level of either FGF receptor gene was not significantly different between tumor tissues and normal tissues.

Blotting, Northern↗
PubMed1991

Analysis of abnormal expression of g-csf gene in a novel tumor cell line (KHC 287) elaborating G-CSF, IL-1 and IL-6 with co-amplification of c-myc and c-ki-ras.

We established a human carcinoma cell line (KHC 287) from a patient with large-cell-typing lung carcinoma associated with marked leukocytosis. The culture supernatant of KHC 287 cells promoted granulocytic colony formation of human bone-marrow cells in semi-solid culture. Colony formation was almost completely suppressed by treatment of the supernatant with a monoclonal anti-granulocyte colony-stimulating factor (G-CSF) antibody. Not only G-CSF but also interleukin-1 alpha (IL-I alpha), IL-I beta and IL-6 were detected in the culture supernatant by an ELISA method. Northern blot analysis of KHC 287 cells revealed distinct expression of these cytokine genes. Southern blot hybridization of KHC 287 DNA showed 20- and 40-fold co-amplification of c-myc and c-ki-ras, respectively. The chloramphenicol acetyl transferase (CAT) activity was distinctly enhanced in the KHC 287 cells which were transfected with the 360 bp upstream region of G-CSF gene inserted into pSV00CAT, but not in non-G-CSF-producing tumor cell lines. These results suggest that overproduction of the transactivating factor(s) which binds to the 360 bp of the G-CSF upstream region is responsible for the abnormal expression of G-CSF gene in KHC 287 cell line.

Base Sequence↗