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Biomedical subjects

A Fujioka

Publications and source records attributed to A Fujioka.

At least 37 records · Page 2Linked to original sources
PubMed1998

A pediatric case of atypical Mycobacterium avium infection of the skin.

We report a case of cutaneous atypical mycobacteriosis in a 12-year-old healthy girl due to Mycobacterium avium. The cutaneous symptoms were three well-defined subcutaneous nodules on both buttocks and on the posterior surface of the left thigh. One had a fistulous opening on the skin surface. Histopathological examination revealed epithelioid cell granulomas surrounded by dense lymphocytic infiltration and acid-fast bacteria were seen with modified periodic acid-carbol fuchsin staining. Using Ogawa's medium at 37 degrees C, acid-fast bacteria were isolated from the biopsied specimen and identified by the DNA-DNA hybridization method as Mycobacterium avium. In drug susceptibility test, these were resistant to all antituberculous drugs. Oral administration of minocycline 100 mg/day for two months had little effect on the two remaining lesions, which were therefore excised. Based upon reported cases of Mycobacterium avium complex, we considered that our pediatric patient with multiple intradermal or subcutaneous nodules on the buttocks and the thigh exhibited the characteristic symptoms of M. avium infection.

Administration, Oral↗
PubMed1998

Relationship between protein levels and gene expression of dihydropyrimidine dehydrogenase in human tumor cells during growth in culture and in nude mice.

Protein levels and gene expression of dihydropyrimidine dehydrogenase (DPD), the rate-limiting enzyme for degradation of 5-fluorouracil, were studied in two human tumor cell lines (fibrosarcoma HT-1080 and pancreatic carcinoma MIAPaCa-2) in various growth phases of the cultured cells and of tumor xenografts implanted into nude mice. DPD catalytic activity and DPD protein content in cytosolic preparations were determined by means of radioenzymatic assay and western blot analysis, respectively. Relative DPD mRNA expression was determined by using a semi-quantitative reverse transcription-polymerase chain reaction in which glyceraldehyde-3-phosphate dehydrogenase mRNA was used as an internal standard. DPD activity and protein content in cultures of both cell lines increased in proportion to cell density (DPD activities ranged from undetectable to 84 pmol/min/mg protein in the HT-1080 cells and from undetectable to 335 pmol/min/mg protein in the MIAPaCa-2 cells). DPD mRNA levels, on the other hand, tended to decrease slightly during cell growth. DPD activity and protein content in HT-1080 tumor xenografts increased during growth in proportion to tumor weight (DPD activities ranged from 7 to 131 pmol/min/mg protein), but DPD mRNA levels did not correlate with tumor weight. DPD activity and protein content in MIAPaCa-2 tumor xenografts did not change much, and seemed to have already plateaued, since the tumors were small (weighing about 30 mg). These findings suggest that DPD protein expression during tumor growth is controlled at the post-transcriptional level.

Animals↗
PubMed1998

Preclinical antitumor efficacy of S-1: a new oral formulation of 5-fluorouracil on human tumor xenografts.

S-1 is a new oral formulation of 5-fluorouracil (5-FU) consisted of 1M tegafur, 0.4M 5-chloro-2,4-dihydroxypyridine that inhibits a degradation of 5-FU, and 1M potassium oxonate that regulates the phosphorylation of 5-FU in the gastrointestinal tract, and has shown excellent antitumor efficacy against various murine tumors in rodents, compared to the oral tegafur-based antitumor drug, UFT (1M tegafur plus 4M uracil), which is used clinically in Japan. To assess the possibility of clinically using S-1, we investigated the antitumor effect of S-1 on various human solid tumor xenografts in athymic rats and mice. In the nude rat system, S-1 was significantly effective against all 12 tumor xenografts tested when its minimum toxic dose (15 mg/kg) was administered for 14 days. Three tumors, stomach (H-81), colon (KM12C) and breast (H-31) markedly regressed in response to treatment with S-1 but not with UFT. The antitumor potency of S-1 was weak against human tumors xenografted into nude mice and likely similar to that of UFT. The reason of the discrepancy in the efficacy of S-1 between rats and mice was found to be that the 5-FU levels in the blood and tumor tissue of rats after oral administration of S-1 persisted much longer than in mice, and this prolonged maintenance of plasma 5-FU levels was significantly related to the potent antitumor activity of S-1. In conclusion, the results of this study suggested that based on its biological and pharmacokinetic characteristics, oral S-1 should be active against various human cancers.

Administration, Oral↗
PubMed1998

[Antitumor activity of miproxifene phosphate (TAT-59) against human mammary carcinoma].

DP-TAT-59, an active metabolite of miproxifene phosphate (TAT-59), showed a strong anti-proliferating activity against ER-positive human mammary carcinoma cell lines, MCF-7 and T-47D, in the presence of 1 nM of estradiol. The ED50 value of DP-TAT-59 for each cell line was 30-fold lower than that of tamoxifen. TAT-59 suppressed the growth of mammary carcinoma, MCF-7 and Br-10, xenografted into nude mouse at a dose of 5 mg/kg/day, which is equivalent to 20 mg/body of daily dose to the patients. TAT-59 inhibited the growth of tamoxifen-resistant breast cancer cell lines, R-27 and FST-1, but not tamoxifen, suggesting the possible efficacy of TAT-59 for tamoxifen-refractory patients. DP-TAT-59 and DM-DP-TAT-59, major metabolites of TAT-59 detected in blood after oral administration in the patients, exhibited equal growth-inhibitory activity against human mammary tumor xenograft, meaning the antitumor activity of TAT-59 may equally depend on these two metabolites. In uterotrophic testing using both immature mice and ovariectomized rats, while the effective dose of TAT-59 was lower than that of tamoxifen, TAT-59 showed dose-dependent estrogenic activity against their uteri, similar to tamoxifen. These results suggested that TAT-59 had a stronger antagonistic activity against estrogen-dependent mammary tumor than tamoxifen. We expect that TAT-59 will become an effective therapeutic agent for patients with high estrogen levels in their blood, such as premenopausal women, and the patients with whom the tamoxifen modality failed.

Animals↗
PubMed1997

Postsurgical oral administration of uracil and tegafur inhibits progression of micrometastasis of human breast cancer cells in nude mice.

We recently established a metastasis model in nude mice using the MKL-4 cell line, a contransfectant of the MCF-7 human breast cancer cell line with fgf-4 and lacZ in which micrometastases in several organs can be quantitatively observed. First, to develop a new postsurgical metastasis model, we investigated the timing of occurrence of micrometastasis and the influence of tumor removal on the progression of micrometastasis in this model. Micrometastases into lymph nodes and lungs were detected 3 weeks after the cell injections. Tumor removal 3 weeks after the injections significantly enhanced the progression of micrometastasis into lymph nodes and bone. Second, to study the effect of a mixed compound, UFT (a molar ratio of uracil:tegafur of 4:1), which has been widely used in the postsurgical adjuvant setting in Japan, 15 or 20 mg/kg UFT were administered p.o. for 4 weeks to tumor-bearing mice or to mice in which transplanted tumors were resected 3 weeks after the injections. Either dose of UFT significantly inhibited the tumor growth as well as the progression of micrometastasis into lymph nodes, lungs, liver, and brain. In addition, enhanced progression of micrometastasis in all explored organs by the tumor removal was significantly inhibited by the administration of either dose of UFT. In conclusion, this new postsurgical metastasis model may be useful for evaluating the efficacy of agents used in the postoperative adjuvant setting. UFT may be an effective drug for inhibiting the progression of micrometastasis after surgery.

Animals↗
PubMed1996

Prolongation of survival period and improvement of cancer cachexia by long-term administration of UFT.

We assayed the antitumoral and anticachectic activity of an oral fluoropyrimidine, UFT using the Colon-26-bearing murine cachexia model in terms of the survival period and parameters corresponding to clinical symptoms. Tumor growth was inhibited by UFT dose-dependently at the dose range of 12.5-25.0 mg/kg per day. Although UFT did not show significant growth inhibition at 15.0 and 12.5 mg/kg to which UFT gave little toxicity, the survival period was shown to be superior to the case of maximum tolerated dose (25.0 mg/kg per day). Next, we compared the maximum increase of life span (ILS) value for an administration schedule of continuous 9 days and 5 weeks which mimics the clinical schedule and found that the ILS value in the latter group was superior to the former and UFT improved cachexia, in the same manner. In the following experiments, we have clarified that UFT decreased the level of both plasma interleukin-6 (IL-6) and tumorous prostaglandin E2 (PGE2) and it highly accelerated IL-6 production from Colon-26. These findings suggest that UFT therapy, in low-toxic dose, could be useful to cachectic patients with poor performance status.

Animals↗
PubMed1996

Antitumor activity of 1 M tegafur-0.4 M 5-chloro-2,4-dihydroxypyridine-1 M potassium oxonate (S-1) against human colon carcinoma orthotopically implanted into nude rats.

The purpose of this study was to establish a nude rat orthotopic (organ-specific) human colorectal cancer model as an in vivo secondary screen for general evaluation of new anticancer agents against colorectal cancer and to evaluate practically the antitumor activity of 1 M tegafur-0.4 M 5-chloro-2,4-dihydroxypyridine-1 M potassium oxonate (S-1), a new p.o. fluoropyrimidine, in comparison to 1 M tegafur-4 M uracil [(UFT) effective on colorectal tumor in clinical]. After implantation of KM12C, a human colorectal cancer cell line, into the subserosal layer of the colon as a single-cell suspension, extensive local tumor growth and invasion to both the mucosal and the serosal sides were observed in all rats. Metastatic foci were also formed in both lymph nodes and lungs following local tumor growth in all of them. Using this method, an equitoxic dose of S-1 (15 mg/kg/day) and UFT (30 mg/kg/day) was administered p.o. for 14 consecutive days from 7 days after tumor cell implantation. S-1 showed a higher tumor growth inhibition than UFT did [S-1, 57% (significantly different from the tumor weight of the untreated group at P < 0.05) and UFT, 18% (P > 0.05)]. When both drugs were administered to nude rats bearing KM12C injected into the cecal wall for 28 consecutive days at equitoxic doses, the mean survival in the S-1 group was 16 days longer than that in the untreated group (P < 0.01) but that in the UFT group was only 8 days longer (P > 0.05). After the administration of an equitoxic dose of both drugs, S-1 gave the higher levels than UFT in various pharmacokinetic parameters as follows: area under the curve 0-24 h of 5-fluorouracil in plasma (3.5-fold), area under the curve 0-24 h of 5-fluorouracil incorporated into RNA in the tumor (1.3-fold), and thymidylate synthase inhibition rate (percentage) in the tumor (about 20%). Collectively, these findings suggested that this orthotopic human colorectal tumor model in nude rats is useful to evaluate the clinical therapeutic efficacy of drugs or therapies for colorectal cancer, and that S-1 had a higher therapeutic effect on human colorectal tumor than UFT did.

Adenocarcinoma↗
PubMed1996

Oncocytic hepatocellular carcinoma with numerous globular hyaline bodies.

Two well circumscribed tumors, oncocytic and non-oncocytic, were removed from the non-cirrhotic liver of a 67 year old male. The large oncocytic tumor (OCT), occupying the entire left lobe, was multilobulated with focal coagulation necrosis and areas of hemorrhage. Light microscopy revealed that it consisted of exclusively large, granular oxyphilic cells with moderate nuclear atypia and occasional mitotic figures, which were trabecular and/or pseudoglandular in structure, but no lamellar fibrosis was seen. Characteristically, the OCT cells included numerous globular hyaline bodies (GHB) of various sizes which were stained red with acid fuchsin and deep blue or magenta with phosphotungstic acid hematoxylin (PTAH), but negative for periodic acid Schiff (PAS), orcein, rhodamine and Grimelius methods. Immunohistochemically, alpha-fetoprotein (AFP), alpha-1-antitrypsin, alpha-1-antichymotrypsin, fibrinogen and ferritin were all negative. On ultrastructural examination, tumor cells were mitochondria-rich, including electron dense, ovoid or polyhedral inclusions, with the delineated membrane identical with that of the GHB. In contrast, the small tumor in the right lobe (Segment 7) was a solid adenoma with no oncocytic transition. Based on these findings, it was postulated that OCT consists of heterogenous proliferation of mitochondria-rich hepatocytes which tend to induce lysosomal GHB closely associated with mitochondrial abnormalities.

Adenocarcinoma↗
PubMed1996

Effects of extracellular matrix macromolecules on the differentiation of plasma membrane structure in cultured astrocytes.

Orthogonal aggregates of small intramembrane particles, termed "assemblies," are concentrated especially in the cell membranes of astrocytic processes that form the glia limitans at the outer surface of the brain and the perivascular sheath surrounding the parenchymal blood vessels. As an initial step to clarifying the totally unknown biochemical nature of this intramembrane structure, we have devised a culture system which enhances the differentiation of assemblies in secondary cultures of astrocytes derived from neonatal mouse neopallium. Since assemblies are most concentrated in the plasma membranes attaching to the basement membrane, we expected that extracellular matrix molecules constituting the basement membrane would be suitable candidates for our aim. We report here that a mixture of type IV collagen, laminin, and fibronectin, major components of the extracellular matrix, has the potency to increase assembly density in cultured astrocytes. We also report that, in freeze-fracture electron microscopy of cultured cells, one can satisfactorily preserve membrane structure and reliably obtain large replicas by inoculating cells on aluminium foil and peeling it from the cells in a freeze-fracture apparatus.

Animals↗
PubMed1996

[Prolongation of survival and antitumor activity of antitumor drugs in murine cancer cachexia model].

We examined the activity of UFT, ADM and MMC, which are used for colon tumors, in terms of their prolongation of the survival period, growth inhibition of the primary tumor and improvement of cachexia in murine cancer cachexia model. The mean survival period of Colon 26, mouse adenocarcinoma bearing mice was 25.0 +/- 4.9 days. The maximal ILS value of the UFT administered group was 103.2%, against 7.2 and 26.0%, respectively, ADM and MMC maximal ILS value. For therapeutic activity of hypercalcemia, UFT was superior to other drugs, although all drugs showed equivalent tumor growth inhibitory activity. These findings indicate that UFT can prolong the survival period due to improvement of cancer cachexia. Therefore, we measured plasma interleukin-6 (IL-6) and found that UFT-administration lowered the plasma IL-6 level more than other drugs. Moreover, the prostaglandin E2 (PGE2) level in the tumor was significantly decreased only by UFT-administration. Since PGE2 has been shown to enhance IL-6 production from Colon 26 in vitro, it was speculated that UFT improve cachexia and prolongs life by decreased IL-6 resulting from decreased PGE2.

Animals↗
PubMed1996

[Inhibition of prostate cancer growth in nude mice by hormone and chemotherapy].

The combined effect of hormone and cytotoxic therapy on the growth of prostate cancer PC-3 in nude mice was investigated. PC-3 cell was derived from the bone metastasis of a hormone-refractory prostate cancer. Each group consisted of seven animals. After the inoculation of cancer cells, diethylstilbestrol (DES: 20 mg/kg) and futraful with uracil (UFT: 20 mg/kg) were administered for 25 days. DES and UFT synergically inhibited the growth. DES had no effect as a single agent on the growth of a hormone-independent cell line (KM20C) derived from human colon cancer. It also had no additive effect when given with UFT.

Animals↗
PubMed1995

[Augmentation of chemotherapeutic efficaciousness of UFT by oral l-leucovorin--growth-inhibitory activity of combination against human tumor xenograft].

Combination chemotherapy with FUra and LV has been reported as a useful treatment for patients suffering from colon carcinoma. Usually, both FUra and LV are administered by intravenous infusion, but not orally. UFT, an anti-neoplastic agent consisting of FT and uracil, is widely used for oral administration in Japan. Using human tumor xenografts of 10 cell lines, we evaluated the efficacy of UFT combined with l-LV, which is the active form of LV, by oral administration. Combined treatment of UFT with l-LV was more effective than UFT alone on the growth suppression of colon carcinoma (KM 20 C, Col-1) and mammary carcinoma (H-31, MX-1). When 1.85 mg/kg (5.55 mg/m2) of LV was given to tumor bearing mice, the antitumor activity of UFT was augmented and at a dose of 5.56 mg/kg (16.7 mg/m2) of LV, it was significantly augmented. Among various 5-FU derivatives, such as UFT, 5'-DFUR or FUra, combined treatment using UFT with l-LV was the most effective by oral administration. l-LV did not improve the anti-tumor efficacy or toxicity of 5'-DFUR. l-LV seemed to augment the anti-tumor activity of FUra, but not significantly. These results suggest that combination chemotherapy of UFT with LV is a promising approach for the clinical treatment of human colon cancer.

Administration, Oral↗
PubMed1994

[Antitumor and anticachectic activity of UFT in BALB/c mice bearing colon 26 adenocarcinoma].

We established a cancer cachexia model in BALB/c mice bearing Colon 26 and examined antitumor and anticachectic activity of UFT. The mice bearing Colon 26 showed a progressive loss of body weight, loss of lipid, and hypalbuminosis associated with the change of tumor size and these symptoms were improved by removal of cancer. In this model UFT extended life span significantly at 15mg/kg/day though showed a little growth inhibitory activity. UFT showed a significant tumor growth inhibitory activity and extended life span at 20mg/kg/day and could reverse all biological parameters mentioned above. Since the intratumor and plasma contents of IL-6 were significantly lowered in the UFT administered group, it is estimated that the anticachectic activity of UFT originates from reduction of interleukin-6 in tumor.

Adenocarcinoma↗
PubMed1993

[Polyneuropathy with IgM-antibody to myelin-associated glycoprotein without detectable M-protein by conventional analysis--report of a case].

A 56-year-old man gradually developed paresthesia and muscular weakness of the left hand and feet for two years. On admission, neurological examination showed predominantly sensory polyneuropathy. Electrophysiological study and sural nerve biopsy demonstrated segmental demyelination, but any underlying congenital, toxic, metabolic or neoplastic cause was failed to reveal. The serum IgM level was 576 mg/dl, while IgG and IgA were normal. An immunoblot analysis and ELISA showed serum IgM antibody that reacted with human MAG. Serum IgM M-protein, however, was detectable not by conventional serum protein electrophoresis and immunoelectrophoresis, but by immunofixation. Anti-MAG antibodies should be evaluated in the patients with slowly progressive demyelinating polyneuropathy of unknown etiology, even if no serum M-protein is detected by conventional methods. Serum M-protein may play a role of pathogenesis of demyelination, and immunofixation method could be beneficial to detect small amount of M-protein.

Autoantibodies↗