PubMed Health⌕ Search

Biomedical subjects

A Hagiwara

Publications and source records attributed to A Hagiwara.

At least 19 recordsLinked to original sources
PubMed1999

Gains, losses, and amplifications of genomic materials in primary gastric cancers analyzed by comparative genomic hybridization.

By means of comparative genomic hybridization (CGH), we screened 58 primary gastric cancers for changes in copy number of DNA sequences. We detected frequent losses on Ip32-33 (21%), 3p21-23 (22%), 5q14-22 (36%), 6q16 (26%), 9p21-24 (22%), 16q (21%), 17p13 (48%), 18q11-21(33%), and 19(40%). Gains were most often noted at I p36 (22%), 8p22-23 (24%), 8q23-24 (29%), 11q12-13 (24%), 16p(21%), 20p (38%), 20q (45%), Xp21-22(38%), and Xq21-23 (43%), with high-level amplifications at 6p21(2%),7q31(10%), 8p22-23(5%), 8q23-24 (7%), 11q13(4%), 12p12-13(4%), 17q21(2%), 19q12-13(2%), and 20q13(2%). High-level amplification at 8p22-23 has never been reported in any other cancer type and its frequency was as high as that reported for the MYC, MET, and KRAS genes. We narrowed down the smallest common amplicon to 8p23.1 by reverse-painting FISH to prophase chromosomes. Southern blot analysis using one EST marker (D38736) clearly demonstrated that amplification of this exon-like sequence had occurred in all three tumors in which amplifications at 8p22-23 had been detected by CGH. Our data provide evidence for several, previously undescribed, genomic aberrations that are characteristic of gastric cancers.

Blotting, Southern↗
PubMed1999

Hepatocarcinogenic activity of N-butyl-N-(4-hydroxybutyl)nitrosamine in rats is not modified by sodium L-ascorbate.

Male F344 and Wistar Shionogi (WS) rats were treated with 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) for 20 weeks and then killed at week 36 (experiment 1). Although reduction of body weight increase was found, no effects on liver weights were noted. Formalin-fixed and paraffin-embedded liver tissues from rats killed terminally were cut and stained for glutathione S-transferase placental form (GST-P) immunohistochemically. Marked elevation of quantitative values of small GST-P positive (GST-P+) foci were apparent in both strains of rat administered BBN. In experiment 2, both sexes of F344 rats were given 0.05% BBN in the drinking water for 4 weeks and then fed diet containing 0 or 5.0% sodium L-ascorbate (SA) for 32 weeks. No body and liver weight changes were evident in any group. Quantitative values for small GST-P+ foci were increased in both sexes of rats exposed to BBN but were not modified by additional SA treatment. Thus, it was confirmed that the selective bladder carcinogen BBN also acts as a liver carcinogen. These results, from the quantitative analysis of small GST-P+ foci as end point marker lesions, indicate that the liver tumor modifying potential of test chemicals can be evaluated in rats by using an initiation/promotion protocol for urinary bladder carcinogenesis.

Animals↗
PubMed1999

No survival benefit from combined pancreaticosplenectomy and total gastrectomy for gastric cancer.

BACKGROUND: It remains unknown whether extended surgery improves the survival rate of patients with gastric cancer. This study was a review of combined pancreaticosplenectomy with total gastrectomy for gastric cancer. METHODS: The clinicopathological details of 190 patients who underwent combined pancreaticosplenectomy with total gastrectomy between 1969 and 1996 were compared retrospectively with those of 206 patients who underwent total gastrectomy with splenectomy alone. RESULTS: There was no statistical difference in the survival rate when pancreaticosplenectomy was added to total gastrectomy. The mortality rate was similar, but the morbidity rate was higher in patients who had pancreaticosplenectomy. Six patients who had direct pancreatic invasion and two thought to have involved lymph nodes along the splenic artery survived for more than 5 years after operation. In the latter group, the metastatic lymph nodes along the splenic artery could have been resected without pancreatectomy. CONCLUSION: Since a combined pancreaticosplenectomy adds no survival advantage to total gastrectomy for gastric cancer, this procedure should no longer be regarded as routine.

Female↗
PubMed1999

Number and anatomical extent of lymph node metastases in gastric cancer: analysis using intra-lymph node injection of activated carbon particles (CH40).

BACKGROUND: The long-term survival of 200 patients with gastric cancer who underwent radical gastrectomy was analyzed with respect to the number and anatomical extent of lymph node metastasis. All of the patients received intra-lymph node injection of fine activated carbon particle solution (CH40) during surgery. METHODS: The average number of resected lymph nodes increased in line with the anatomical level of lymph node dissection; 32.5 per patient in D1, 42.3 in D2, 3 and 66.3 in D4. The percentage of blackened lymph nodes without metastasis (42.4%) was slightly higher than that of lymph nodes containing metastasis (37.2%), but the difference was not statistically significant. Of the 200 patients, 61 (30.5%) had microscopic evidence of metastatic lymph node involvement. Twenty-two patients had between one and three metastatic lymph nodes, 19 had between four and nine and 20 patients had more than nine. The 5-year survival rate was 93.1% in patients without lymph node metastasis, 71.9% in patients with 1-8 metastatic nodes, 36.1% in patients with 4-9 nodes and 19.2% in patients with > 9 nodes. RESULTS: The 5-year survival rate according to the anatomical extent of metastatic lymph nodes was 93.1% in n0, 63.1% in n1, 37.9% in n2, 27.8% in n3 and 0% in n4. The number of metastatic lymph nodes and also their anatomical extent were identified as independent prognostic factors for survival by multivariate analysis. CONCLUSION: The number and anatomical extent of metastatic lymph nodes have similar impacts on prognosis in gastric cancer.

Adult↗
PubMed1999

Evaluation of an enzyme-linked immunosorbent assay based on binding inhibition for type-specific quantification of poliovirus neutralization-relevant antibodies.

To detect neutralization-relevant antibodies against 3 types of poliovirus (PV) without using tissue cultures and live viruses, an enzyme-linked immunosorbent assay (ELISA) based on monoclonal antibody-binding inhibition was evaluated using sera from 80 vaccinated Japanese children and 60 Pakistani poliomyelitis patients. Compared with the neutralization test, the sensitivity of the inhibition ELISA was 100% (111/111) for detection of anti-PV1 antibody, 98.3% (118/120) for anti-PV2, and 96.5% (82/85) for anti-PV3, and the specificity was 93.1% (27/29), 100% (20/20), and 92.7% (51/55), respectively. Thus, the inhibition ELISA showed excellent potential as a seroepidemiologic tool in both vaccinated and naturally-infected populations.

Animals↗
PubMed1999

Organ-dependent modifying effects of caffeine, and two naturally occurring antioxidants alpha-tocopherol and n-tritriacontane-16,18-dione, on 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-induced mammary and colonic carcinogenesis in female F344 rats.

Modifying effects of caffeine, alpha-tocopherol, and n-tritriacontane-16,18-dione (TTAD) on 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-induced mammary and colonic carcinogenesis were investigated in female F344 rats. Groups of 20 rats, 6 weeks old, were given 0.02% PhIP (in diet) alone, or together with 0.1% caffeine (in drinking water), 0.5% alpha-tocopherol (in diet) or 0.1% TTAD (in diet) for up to 54 weeks. Groups of 10 females receiving basal diet or one of the test chemicals without PhIP supplementation were also maintained. The final combined incidences (adenomas plus adenocarcinomas) and multiplicity (No./rat) of mammary adenomas and adenocarcinomas were significantly lowered in the PhIP plus caffeine group (10%, 0.10) as compared to the PhIP alone value (40%, (1.50). Incidences of mammary tumors in the PhIP plus alpha-tocopherol or TTAD groups tended to be decreased while their multiplicities were significantly lowered. With regard to colon tumor development, on the other hand, rats given PhIP plus caffeine exhibited an elevated incidence (75% versus 15% in the control), whereas alpha-tocopherol and TTAD had no effect. Surprisingly, metabolic activation of PhIP was inhibited by addition of caffeine in an in vitro assay. The results indicate that caffeine exerts a potent chemopreventive action against PhIP-induced mammary carcinogenesis, but acts as a co-carcinogen for PhIP-induced colonic carcinogenesis.

Adenocarcinoma↗
PubMed1999

[Development of cancer treatment practice guidelines in Japan: advantages and disadvantages].

The development of clinical practice guidelines for the systematic treatment of cancer is being promoted as a way to assist clinicians and patients. In this paper, the advantages and disadvantages of developing clinical practice guidelines for both clinicians and patients are discussed. Physicians may regard guidelines to be unrealistic, and some may even consider guidelines to be a challenge to their autonomy. However, the advantages of guidelines for the patients and clinicians exceed any disadvantages. The development of guidelines should therefore be promoted, although with consideration of both the many advantages and disadvantages for clinicians and patients.

Diagnosis-Related Groups↗
PubMed1999

[Treatment of postoperative recurrence of digestive cancers: peritonitis carcinomatosa].

Carcinomatous peritonitis is the most frequent type of recurrence observed after surgery for cancer of the digestive tract. Most patients with carcinomatous peritonitis present with bowel obstruction and/or ascites. Surgical treatment including colostomy and intestinal anastomosis and chemotherapy have been attempted in patients with carcinomatous peritonitis, although the results have not been satisfactory. New drug delivery systems, such as mitomycin C-adsorbed charcoal, anticancer drugs entrapped in microspheres, and immunoconjugates composed of anticancer drugs and antibodies, will be powerful new tools for the treatment of metastatic cancer.

Digestive System Neoplasms↗
PubMed1998

Selectivity of sphingosine-induced apoptosis. Lack of activity of DL-erythyro-dihydrosphingosine.

Sphingosine (Sph) is emerging as an intracellular regulator of cellular differentiation and apoptosis (Ohta, et al., Cancer Res., 55, 691-697, 1995). We have recently found that both Sph and its methylated derivative N,N-dimethylsphingosine (DMS) inhibit mitogen-activated protein kinase (MAPK) activity, suggesting that Sph-induced apoptosis may be mediated at least partly through inhibition of MAPK (Sakakura, et al., Int J Oncol, 11, 31-39, 1997). We report in this study that three stereoisomers, D-erythro-Sph, L-threo-Sph, and DL-erythro-dihydrosphingosine, were tested in induction of apoptosis and inhibition of MAPK activity in three different kinds of solid tumor cell lines. D-erythro-Sph was strongest in these effects among three compounds. L-threo-Sphingosine was partly active. On the other hand, DL-erythro-dihydrosphingosine was totally inactive. These results demonstrate the specificity of sphingosine action in induction of apoptosis and inhibition of MAPK, suggesting that Sph may play an important role as a physiological intracellular messenger of apoptosis in these cancer cells.

3T3 Cells↗
PubMed1998

Recent advances in surgical treatment have improved the survival of patients with gastric carcinoma.

BACKGROUND: Mortality resulting from gastric carcinoma is decreasing. This is mainly due to vigorous endoscopic screening and the consequent higher incidence of early detection of the disease. In this study, to evaluate the effect of surgical treatment on the prognoses of patients with gastric carcinoma, the survival of 1579 patients who underwent gastrectomy between 1970 and 1994 was retrospectively analyzed. METHODS: The patients were divided into 5 groups at 5-year intervals. Postoperative survival was compared among the groups. RESULTS: Postoperative survival was significantly improved in the later groups for patients with Stage I, II, III, and IV disease. A multivariate analysis of prognostic factors revealed that the time period during which the gastrectomy was performed was an independent predictor of survival. CONCLUSIONS: It was concluded that survival has been improved by recent advances in the surgical approach to gastric carcinoma.

Carcinoma↗
PubMed1998

Variation in susceptibility to the induction of forestomach tumours by butylated hydroxyanisole among rats of different strains.

The forestomach carcinogenicity of butylated hydroxyanisole (BHA) was compared in males of the F344, SHR, Lewis and Sprague Dawley rat strains. Groups of 30 6-wk-old animals were given a pellet diet containing 2% BHA for 104 wk. Forestomach squamous cell papillomas and hyperplasias developed in all rats given BHA, independent of the strain, but the incidences of squamous cell carcinomas (SCCs) differed considerably: F344, 26.7% (8/30) SHR, 76.7% (23/30) SD, 36.7% (1130) Lewis, 6.7% (2/30). Cytotoxic effects, reflected by inflammation, were also most severe in the SHR strain, correlating well with the development of SCCs. The present results indicate that major strain differences exist regarding BHA rat forestomach carcinogenesis and that sensitivity to cytotoxicity might be an important parameter.

Animals↗
PubMed1998

Analysis of histological therapeutic effect, apoptosis rate and p53 status after combined treatment with radiation, hyperthermia and 5-fluorouracil suppositories for advanced rectal cancers.

The tumour-suppressor gene p53 encodes a transcription factor that plays a critical role in the induction of G1 cell cycle arrest and apoptosis after DNA damage. To clarify the role of the p53 gene and apoptosis in combined hyperthermia, chemotherapy and radiation (hyperthermochemoradiotherapy, HCR therapy) for rectal cancer, we examined the histological response, rate of apoptosis, DNA fragmentation and p53 status in tumours from 28 patients undergoing HCR therapy before surgery and from 22 patients who did not have preoperative treatment. The therapeutic effect of HCR therapy was closely correlated with the rate of apoptosis; the correlation was statistically significant, suggesting that this effect occurs through apoptosis. The incidence of p53 mutations in the treated group were as follows: in tumours resistant to HCR therapy, four of seven (57.1%); intermediately sensitive, 7 of 13 (53.9%); or sensitive, three of eight (37.5%), suggesting that the therapeutic effect and apoptosis rate were related to the p53 status of the tumours to some extent, but the relation was not statistically significant. In the 22 control tumours (non-treated group), the apoptosis rate was 2.0 +/- 1.1%, and there was no significant difference in p53 status compared with the HCR group. Our study indicates that the pathological response to HCR therapy correlates with the rate of apoptosis with statistical significance and that it induces the therapeutic effect more significantly in rectal cancer cells with wild-type p53, although HCR therapy-induced apoptosis also occurs in some rectal cancers with mutated p53. Therefore, this combination therapy can induce an additive or synergistic anti-tumour effect in rectal cancers with wild-type p53 as well as in those with mutated p53 through apoptosis, offering new therapeutic opportunities and a better prognosis.

Antimetabolites, Antineoplastic↗
PubMed1998

Presence of a threshold for promoting effects of phenobarbital on diethylnitrosamine-induced hepatic foci in the rat.

The dose dependence of the hepatopromoting effects of phenobarbital (PB) was investigated in a rat liver medium-term bioassay (Ito test) to elucidate a practical threshold level. F344 rats were given a single i.p. injection of diethylnitrosamine (200 mg/kg body wt) and subjected to two-thirds partial hepatectomy at week 3. Commencing 2 weeks from the start, PB at doses of 0, 1, 2, 4, 7.5, 15 or 500 p.p.m. in experiment 1 and 0, 0.01, 0.1 or 0.5 p.p.m. in experiment 2 were fed to the rats for 6 weeks. Experiment 3 was conducted to confirm previous data using the same medium-term bioassay, with PB at doses of 0, 1, 2, 4, 7.5, 15, 30, 60, 125, 250 or 500 p.p.m. fed to the rats. All surviving animals were killed at week 8 in these experiments and their livers were immunohistochemically examined for expression of glutathione S-transferase placental form (GST-P). Quantitative values for GST-P-positive foci in the liver were increased dose dependently in rats given 60-500 p.p.m. PB. However, those for doses in the range 1-7.5 p.p.m. demonstrated a decrease as compared with the control group (0 p.p.m.), with significant differences observed for 1 and 2 p.p.m.. The results for 15-30 and 0.01-0.5 p.p.m. were comparable with the control values. Examination of transforming growth factor-alpha (TGF-alpha)-positive foci also produced similar results to those for GST-P in experiment 1. Immunohistochemical staining of TGF-alpha and GST-P using serial liver sections demonstrated that the TGF-alpha-positive foci comprised a sub-population of the GST-P-positive lesions, being approximately 1/8-1/10th as common in livers of animals treated with PB. TGF-alpha-positive foci were almost always negative on immunostaining for TGF-beta. Western blotting for proteins CYP2B1, 2C6 and 3A2 revealed a good correlation between changes in GST-P-positive foci and CYP3A2 protein expression. The finding of inhibition effects at low doses of PB confirms the presence of a threshold level for promoting effects by PB on liver carcinogenesis in rats.

Animals↗
PubMed1998

Ca2+-induced distance change between points on actin and troponin in skeletal muscle thin filaments estimated by fluorescence energy transfer spectroscopy.

Fluorescence resonance energy transfer spectroscopy has been used to study the spatial relationships between probes attached to actin and troponin in the reconstituted skeletal muscle thin filament in the presence and absence of Ca2+ ions. Gln-41 and the nucleotide-binding site of actin were selectively labeled with the acceptor probe: fluorescein cadaverine and 2'(or 3')-O-(2,4,6-trinitrophenyl)adenosine 5'-diphosphate (TNP-ADP), respectively. Troponin was selectively labeled at positions 9 or 133 of troponin-I and 98 of troponin-C with a donor probe; 5-(2-iodoacetylaminoethyl)aminonaphthalene 1-sulfonic acid (IAEDANS). The distances between probes attached to position 133 of TnI and Gln-41 or the nucleotide site of actin were determined to be 51.6+/-1.2 and 42.7+/-0.9 A respectively in the presence of Ca2+, and these distances decreased by 11.5 and 9.3 A respectively in the absence of Ca2+ ions. The distances between the probes attached to position 9 of TnI and Gln-41 or the nucleotide site of actin were determined to be 59.1+/-2.0 or 49.3+/-1.5 A respectively in the presence of Ca2+, and the distances decreased by 5.3 or 3.7 A in the absence of Ca2+. The distances between probes attached to position 98 of TnC and Gln-41 or the nucleotide site of actin were determined to be 55.1+/-1.7 and 57+/-5 A in the presence of Ca2+ and the distances increased slightly by approximately 1 A in the absence of Ca2+. The results suggest that the C-terminal domain of troponin I moves to the outer domain of actin during inhibition, while the C-terminal domain of TnC does not move much.

Actin Cytoskeleton↗
PubMed1998

Therapeutic effects of 5-fluorouracil microspheres on peritoneal carcinomatosis induced by Colon 26 or B-16 melanoma in mice.

The delivery formulation 5-FU-MS [5-fluorouracil (5-FU) incorporated in microspheres composed of a poly(glycolide-co-lactide) matrix] slowly releases 5-FU over 3 weeks. 5-FU-MS delivers higher concentrations of the drug to the i.p. tissues for a longer period of time with lower blood plasma concentrations than does an aqueous 5-FU solution and reduces toxicity. In this study, we evaluated the therapeutic effects of 5-FU-MS on peritoneal carcinomatosis in mice. Four days after an i.p. inoculation with Colon 26 or B-16 PC melanoma, 5-FU at 200 mg/kg was administered i.p. as 5-FU-MS or as an aqueous solution of 5-FU. 5-FU-MS extended the survival of mice bearing Colon 26 or B-16 PC melanoma significantly better than the equivalent dose of aqueous 5-FU solution.

Animals↗
PubMed1998

A pilot study of fiberscopy-guided local injection of anti-cancer drugs bound to carbon particles for control of rectal cancer.

Rectal cancer patients with contra-indicatory risks may not be able to undergo surgery. In these cases the preferred treatment is chemotherapy. The present dosage formulation, consisting of an anti-cancer drug bound to activated carbon particles, was designed to deliver the anti-cancer drug at high concentration selectively to the injection site as well as to the regional lymph nodes and to improve survival of mice bearing cancer with nodal metastases, as compared to the same dose of aqueous anti-cancer drug in animal experiments. The present clinical trial includes two patients with histologically confirmed adenocarcinoma of the rectum and who had risks contra-indicating surgery. Carbon particles adsorbing anti-cancer drugs totaling 400 mg of methotrexate and 32 mg of mitomycin C in one patient and 100 mg of methotrexate and 8 mg of mitomycin C in another patient were injected into the cancer tissue under guidance of a colono-fiberscope. The rectal cancers were successfully reduced in size and controlled over 2 years or 6 months until the patients died from other causes. Side effect was mild. Local injection of this dosage formulation will be useful for the control of rectal cancer in patients who cannot undergo surgery.

Aged↗
PubMed1998

Hyperechoic appearance of hepatic parenchyma on ultrasound examination of patients with blunt hepatic injury.

OBJECTIVE: To study the significance of a geographic hyperechoic liver parenchyma pattern on ultrasound (US) examination of patients with blunt abdominal injury. DESIGN: Prospective clinical study with double-blind evaluation of images and clinical data. METHODS AND MAIN RESULTS: We performed US examinations in 831 consecutive patients admitted to our hospital for blunt abdominal trauma and identified 33 with a geographic hyperechoic pattern in the liver. We correlated the appearance with computed tomographic images and with clinical, angiographic, and scintigraphic data. All patients with a geographic hyperechoic pattern showed mild computed tomographic evidence of hepatic injury (Mirvis grade 2, 69%; Mirvis grade 3, 31%). Excluding patients who required urgent surgery for other reasons and patients in shock, patients with the geographic hyperechoic pattern were managed conservatively with no complications. CONCLUSION: The geographic hyperechoic pattern of liver parenchyma on US examination of trauma patients is a mild injury that, of itself, does not require surgical therapy.

Adolescent↗