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Biomedical subjects

M Kitajima

Publications and source records attributed to M Kitajima.

At least 73 records · Page 4Linked to original sources
PubMed2000

Integrin alpha6beta4 as a suppressor and a predictive marker for peritoneal dissemination in human gastric cancer.

BACKGROUND & AIMS: Because alterations of integrin expression in cancers contribute to cancer cell biology, we analyzed the association between the potential for peritoneal dissemination and integrin expression. METHODS: The dissemination potential of 10 human gastric cancer cell lines in mice with severe combined immunodeficiency (SCID) was compared with the expression of various integrins. The relationship between integrin expression and peritoneal dissemination was also investigated in surgically resected gastric cancer cases. RESULTS: The level of integrin beta4 subunit expression was inversely correlated with dissemination potential. Introduction of a full-length complementary DNA (cDNA) for beta4 subunit into cancer cells showing negligible beta4 subunit expression markedly suppressed peritoneal dissemination and inhibition of endogenous integrin alpha6beta4 by introduction of a cytoplasmic domain-deleted beta4 subunit cDNA into cells showing high expression of beta4 subunit promoted peritoneal dissemination. Apoptosis, which was histologically evident in peritoneal nodules of SCID mice, was induced in the cells with high beta4 subunit expression by attachment to laminin and stimulation with growth factors in vitro. An immunohistochemical study of specimens from 120 cases of primary gastric cancer showed that patients with beta4 subunit-positive tumors exhibited peritoneal dissemination only infrequently (P < 0.0001) and had a better outcome (P < 0.01). CONCLUSIONS: These results indicate that integrin alpha6beta4 is both a suppressor and a predictive marker for peritoneal dissemination in gastric cancer.

Animals↗
PubMed2000

The role of the sentinel lymph node in gastrointestinal cancer.

Evaluation of the clinical significance of the sentinel node concept in GI cancer has just begun. The authors' preliminary data, using intraoperative radiation techniques and the gamma probe, suggest that it is worthwhile to continue the evaluation of this procedure to determine its role in an accurate staging and a minimally invasive approach to GI cancers.

Feasibility Studies↗
PubMed2000

Artoindonesianin C, a new xanthone derivative from Artocarpus teysmanii.

A new xanthone derivative, artoindonesianin C (1), was isolated from Artocarpus teysmanii, together with two known prenylated flavonoids, cycloartobiloxanthone and artonin J. The structure of artoindonesianin C (1) was determined on the basis of MS and NMR evidence and by comparison with known related compounds.

Animals↗
PubMed2000

Matrix metalloproteinase expression in cultured human gastric wall fibroblasts--interactions with Helicobacter pylori isolated from patients with ulcers.

BACKGROUND: Matrix metalloproteinases (MMPs), enzymes capable of degrading collagens and other extracellular matrix components, have been implicated in gastric ulcer formation. However, the effect on MMP expression of Helicobacter pylori, also implicated in these lesions, has not been studied to our knowledge. AIM: To seek links between H. pylori and MMP expression likely to affect gastric ulcer formation. After fibroblasts from human gastric wall were cocultured with H. pylori. concentrations of MMP-1 and -2 in the medium were determined by enzyme-linked immunosorbent assays. RESULTS: Whereas MMP-1 was not detected in media from fibroblasts or H. pylori culture alone, MMP-1 was detected in cocultures (P<0.01). Similar amounts of MMP-2 were detected in medium from fibroblasts cultured alone and with H. pylori. No MMP-2 production by H. pylori cultured alone was detected. CONCLUSIONS: MMP-1 appears to be important in gastric ulcer pathogenesis, and MMP-1 induction by H. pylori may impede gastric ulcer healing.

Cells, Cultured↗
PubMed2000

Surgery for gastric carcinoma in patients more than 85 years of age.

BACKGROUND: The incidence of gastric carcinoma is increasing in elderly patients. It has not been determined whether surgery improves the quality of life or prolongs survival in patients older than 85 years. This study was designed to evaluate surgery as a treatment option in patients more than 85 years of age. METHODS: The records of 18 patients aged 85 to 91 years (mean 87.3 years), who underwent surgery for gastric carcinoma between 1983 and 1997 were analysed. RESULTS: Three patients had multiple lesions. A total of 21 lesions were examined. Operative procedures included distal gastrectomy (n = 12), total gastrectomy (n = 4), proximal gastrectomy (n = 1), and laparoscopic wedge resection (n = 1). Perigastric lymphadenectomy was performed in 15 patients. No lymph node dissection was performed in three patients. Postoperative complications, including delirium, respiratory dysfunction, cardiac dysfunction, anastomotic leakage, bleeding, and ileus, occurred in 11 patients. There were two hospital deaths in patients who underwent emergency surgery. Survival was neither shortened nor prolonged by surgery as determined by life table analysis. CONCLUSIONS: Surgical treatment should not be avoided based solely on the age of the patient, and quality of life in this population may be improved by surgery. Careful patient selection should include an assessment of the will to live.

Adenocarcinoma↗
PubMed2000

Immunosuppressive therapy using FTY720 combined with tacrolimus in rat liver transplantation.

BACKGROUND: FTY720 (FTY) exerts its effects through a reduction of peripheral lymphocytes. This unique mechanism allows for a possible combination effect with other immunosuppressants. We investigated therapy with FTY combined with tacrolimus (FK) in rat liver transplantation. METHODS: Different doses of FK, FTY, or both were orally administered to the recipients for 15 days. Expression of cytokine mRNAs using RT-PCR and appearance of lymphocyte apoptosis by immunohistologic staining were studied in the allografts. RESULTS: Recipients treated with a low dose of FK (0.3 mg/kg) or FTY (0.03 mg/kg) showed a slightly prolonged survival time, although combination therapy with these drugs prolonged survival time similar to the duration obtained by an optimal dose of each drug alone. A marked suppression of lymphocyte infiltration and decreased levels of mRNAs for IL-2, IFN-gamma, and granzyme B were seen in the grafts with combination therapy. Grafts with combination therapy showed an increased number of cells double-stained with TUNEL and CD2 in infiltrated lymphocytes. CONCLUSIONS: Allografts that underwent combination therapy demonstrated markedly reduced lymphocyte infiltration; a number of cells had induced apoptosis and an inhibition of IL-2, IFN-gamma, and granzyme B mRNA transcription, but not IL-4 and IL-10 transcripts, accounting for powerful mutual effect of FTY and FK.

Animals↗
PubMed2000

Improvement in the results of surgical treatment of advanced squamous esophageal carcinoma during 15 consecutive years.

OBJECTIVE: To document the clinicopathologic characteristics and survival of patients undergoing esophagectomy for squamous carcinoma of the thoracic esophagus, and to examine the factors contributing to improvements in outcome noted in patients with advanced carcinoma. SUMMARY BACKGROUND DATA: Japanese and some Western surgeons recently have reported that radical esophagectomy with extensive lymphadenectomy conferred a survival advantage to patients with esophageal carcinoma. The factors contributing to this improvement in results have not been well defined. METHODS: From 1981 to 1995, 419 patients with carcinoma of the thoracic esophagus underwent esophagectomy at the Keio University Hospital. The clinicopathologic characteristics and survival of patients treated between 1981 and 1987 were compared with those of patients treated between 1988 and 1995. Multivariate analysis using the Cox regression model was carried out to evaluate the impact of 15 variables on survival of patients with p stage IIa to IV disease. Several variables related to prognosis were examined to identify differences between the two time periods. RESULTS: The 5-year survival rate for all patients was 40.0%. The 5-year survival rate was 17.7% for p stage IIa to IV patients treated during the earlier period and 37.6% for those treated during the latter period. The Cox regression model revealed seven variables to be important prognostic factors. Of these seven, three (severity of postoperative complications, degree of residual tumor, and number of dissected mediastinal nodes) were found to be significantly different between the earlier and latter periods. CONCLUSIONS: The survival of patients undergoing surgery for advanced carcinoma (p stage IIa to IV) of the thoracic esophagus has improved during the past 15 years. The authors' data suggest that this improvement is due mainly to advances in surgical technique and perioperative management.

Adult↗
PubMed2000

Dihydropyrimidine dehydrogenase and messenger RNA levels in gastric cancer: possible predictor for sensitivity to 5-fluorouracil.

We investigated the correlation between tumor sensitivity to 5-fluorouracil (5-FU) and enzymatic activities of thymidylate synthetase (TS) and dihydropyrimidine dehydrogenase (DPD) in human gastric cancer specimens. Forty-one patients with advanced gastric cancer gave informed consent and were enrolled in the study. Biopsy specimens of gastric cancer were obtained preoperatively through gastrofiberscopy and used to determine TS and DPD messenger RNA (mRNA) levels. TS and DPD enzyme activity and mRNA levels were also measured in resected tumor tissue samples obtained after surgical resection. TS and DPD activity were measured using the TS-binding assay and a radioenzymatic assay, respectively, while mRNA levels were measured by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR), with co-amplification of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as an internal standard. 5-FU sensitivity of resected tumor specimens was measured by the tetrazolium-based colorimetric assay (MTT assay). Both TS and DPD mRNA levels correlated well between biopsied and resected tumor specimens. A statistically significant correlation was also observed between mRNA levels in biopsied specimens and enzymatic activities in resected specimens. DPD levels significantly correlated with 5-FU sensitivity, such that high DPD activity and high DPD mRNA levels resulted in low sensitivity to 5-FU. In contrast, no correlation was observed between TS activity or TS mRNA levels and 5-FU sensitivity. We conclude that tumor DPD mRNA level, as assessed from biopsy specimens obtained by gastrofiberscopy, may be a useful indicator in predicting tumor sensitivity to 5-FU in patients with gastric cancer.

Antimetabolites, Antineoplastic↗
PubMed2000

UCN-01 (7-hydroxystaurosporine) enhances 5-fluorouracil cytotoxicity through down-regulation of thymidylate synthetase messenger RNA.

UCN-01 (7-hydroxystaurosporine) is a newly developed cell cycle inhibitor known to have several modes of action, including inhibition of cyclin-dependent kinase, induction of p21 and suppression of pRb phosphorylation. In order to test a combination therapy of UCN-01 and 5-fluorouracil (5-FU), growth inhibition of CRL 1420 (MIA PaCa-2; undifferentiated pancreatic carcinoma) by four different treatments was measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. The treatments used were UCN-01 alone, 5-FU alone, 5-FU followed by UCN-01 (5-FU/UCN-01) and UCN-01 followed by 5-FU (UCN-01/5-FU). We also assessed changes in thymidylate synthetase (TS) mRNA levels, TS activity, and 5-FU incorporation by RNA (F-RNA) for each treatment. Although treatment with UCN-01 alone, 5-FU alone, and 5-FU/UCN-01 inhibited CRL 1420 growth in a concentration-dependent manner, treatment with UCN-01/5-FU inhibited the growth of CRL 1420 synergistically at less than 1 microg/ml drug concentration. The down-regulation of TS mRNA by UCN-01 resulted in stable total TS and decreased free TS, and UCN-01/ 5-FU resulted in enhanced thymidylate synthetase inhibition rate (TSIR) compared to UCN-01 alone and 5-FU/UCN-01. This increased TSIR due to UCN-01 pretreatment was accompanied by elevated F-RNA concentrations in the UCN-01/5-FU treatment. The suppression of TS mRNA and TS activity by UCN-01 may lead to higher sensitivity of tumor cells to 5-FU and may explain the synergistic antitumor effect of UCN-01/5-FU. In conclusion, low concentrations of UCN-01 (from 0.01 to 1 microg/ml) may be clinically useful, affording low cytotoxicity of UCN-01, while enhancing the antitumor effect of 5-FU.

Alkaloids↗
PubMed2000

Overexpression of truncated IkappaBalpha induces TNF-alpha-dependent apoptosis in human vascular smooth muscle cells.

Dysregulation of apoptosis is one of the likely underlying mechanisms of neointimal thickening, a disorder in which proinflammatory cytokines may influence the function of vascular smooth muscle cells (VSMCs) and contribute to atherogenesis. One of these cytokines, tumor necrosis factor-alpha (TNF-alpha), induces 2 possibly conflicting pathways, 1 leading to the activation of nuclear factor-kappaB (NF-kappaB) and the other leading to caspase-mediated apoptosis. We investigated whether specific inhibition of NF-kappaB affects TNF-alpha-dependent apoptosis in human VSMCs. To inhibit NF-kappaB activation specifically, we constructed a recombinant adenovirus vector expressing a truncated form of the inhibitor protein IkappaBalpha (AdexIkappaBDeltaN) that lacks the phosphorylation sites essential for activation of NF-kappaB. The IkappaBDeltaN was overexpressed by adenoviral infection and was resistant to stimulus-dependent degradation. Electromobility gel shift and luciferase assays demonstrated that overexpression of IkappaBDeltaN inhibited NF-kappaB activation induced by TNF-alpha or interleukin-1beta (IL-1beta). In cells overexpressing IkappaBDeltaN, TNF-alpha dramatically induced apoptosis, whereas IL-1beta had no effect. The induction was suppressed by treatment with a selective inhibitor of the caspase-3 family, Z-DEVD-fmk, and the overexpression of IkappaBDeltaN induced TNF-alpha-mediated caspase-3 and caspase-2 activity. These results indicate that overexpression of IkappaBDeltaN induces TNF-alpha-dependent apoptosis by efficient and specific suppression of NF-kappaB and upregulation of caspase-3 and caspase-2 activity in human VSMCs. Our findings suggest that adenovirus-mediated IkappaBDeltaN gene transfer may be useful in the treatment of disorders associated with inflammatory conditions, such as the response to vascular injury and atherosclerosis.

Adenoviridae↗
PubMed2000

Effects of Uncaria tomentosa total alkaloid and its components on experimental amnesia in mice: elucidation using the passive avoidance test.

The effects of Uncaria tomentosa total alkaloid and its oxindole alkaloid components, uncarine E, uncarine C, mitraphylline, rhynchophylline and isorhynchophylline, on the impairment of retention performance caused by amnesic drugs were investigated using a step-down-type passive avoidance test in mice. In this test, the retention performance of animals treated with the amnesic and test drugs before training was assessed 24 h after training. Uncaria tomentosa total alkaloid (10-20 mg kg(-1), i.p.) and the alkaloid components (10-40 mg kg(-1), i.p.), as well as the muscarinic receptor agonist oxotremorine (0.01 mg kg(-1), i.p.), significantly attenuated the deficit in retention performance induced by the muscarinic receptor antagonist scopolamine (3 mg kg(-1), i.p.). The effective doses of uncarine C and mitraphylline were larger than those of other alkaloid components. Uncarine E (20 mg kg(-1), i.p.) also blocked the impairment of passive avoidance performance caused by the nicotinic receptor antagonist mecamylamine (15 mg kg(-1), i.p.) and the N-methyl-D-aspartate (NMDA) receptor antagonist (+/-)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP; 7.5 mg kg(-1), i.p.), but it failed to affect the deficit caused by the benzodiazepine receptor agonist diazepam (2 mg kg(-1), i.p.). Rhynchophylline significantly reduced the mecamylamine-induced deficit in passive avoidance behaviour, but it failed to attenuate the effects of CPP and diazepam. These results suggest that Uncaria tomentosa total alkaloids exert a beneficial effect on memory impairment induced by the dysfunction of cholinergic systems in the brain and that the effect of the total alkaloids is partly attributed to the oxindole alkaloids tested. Moreover, these findings raised the possibility that the glutamatergic systems are implicated in the anti-amnesic effect of uncarine E.

Alkaloids↗
PubMed2000

A new gluco indole alkaloid, 3, 4-dehydro-5-carboxystrictosidine, from Peruvian Uña de Gato (Uncaria tomentosa).

A new gluco indole alkaloid, 3,4-dehydro-5-carboxystrictosidine, was obtained from Peruvian Uña de Gato (Cat's Claw, original plant: Uncaria tomentosa) together with two known gluco indole alkaloids. This compound was the first example of isolation of a gluco monoterpenoid indole alkaloid having a 3,4-dihydro-beta-carboline ring system from nature. A characteristic feature of the compound was the quick replacement of the methylene hydrogens on C-14 with deuterium that was observed when it was dissolved in CD3OD. We demonstrated a similar proton-deuterium exchange on a model compound, 1-methyl-3,4-dihydro-gamma-carboline, in CD3OD solution.

Alkaloids↗
PubMed2000

What's new in imaging? New magnetic resonance imaging of esophageal cancer using an endoluminal surface coil and antibody-coated magnetite particles.

An endoluminal surface coil: Esophageal cancer was studied by high resolution magnetic resonance imaging (MRI) to determine the histopathologic basis for signal intensity in these lesions and to determine the potential of this modality for evaluating the depth of cancer invasion. In a basic study, 14 tumors were examined with a 1.5-T superconductive MR system using a surface coil. The esophageal wall could be differentiated into four layers on the T1-weighted images and seven layers on the T2-weighted images. The signal intensity of the tumor varied from low to intermediate on the T1- and T2-weighted images. The submucosal layer is important in evaluating cancer invasion on the T2-weighted images. In a clinical study, 30 patients with esophageal cancer were examined with a 1.5-T superconductive MR system using an endoluminal surface coil. In terms of depth of cancer invasion, the accuracy rate of MRI using the endoluminal surface coil was 83%. In conclusion, MRI with an endoluminal surface coil will be a useful examination for esophageal cancer in the future. Antibody-coated magnetite particles: A highly specific and effective MRI contrast agent was prepared by coating superparamagnetite particles with monoclonal antibodies (MAbs) directed against epidermal growth factor receptors (EGFRs), which are overexpressed in esophageal squamous cell carcinoma. The agent was shown to have EGFR-specific MRI contrast capacity in vivo in athymic rats bearing TE8 or H69 tumors. Immunospecific MRI using magnetite particles coated with MAbs against EGFR seems to be useful in the diagnosis of squamous cell carcinoma of the esophagus.

Animals↗
PubMed2000

Vascular endothelial growth factor expression predicts outcome and lymph node metastasis in squamous cell carcinoma of the esophagus.

Vascular endothelial growth factor (VEGF) expression and tumor microvessel density (MVD) were examined by immunohistochemical staining in 117 cases of thoracic esophageal squamous cell carcinoma. Thirty-six (31%) of the 117 cases were evaluated as VEGF-positive. The average number of metastatic lymph nodes at surgery was 5.6 in the VEGF-positive cases and 3.0 in the VEGF-negative cases and was significantly higher in those with VEGF-positive cases (P = 0.04). The incidence of pathological tumor (PT)2-4 cases among the high-MVD cases was significantly higher than among the low-MVD cases (P = 0.01). MVD was 59.4 +/- 4.7 (mean +/- SE)/mm2 in the VEGF-positive cases and 47.9 +/- 3.8/mm2 in the VEGF-negative cases. The MVD of the VEGF-positive tumors was higher than that of VEGF-negative tumors, but the difference was not significant (P = 0.08). The survival rate of the patients with high-MVD tumors was significantly poorer than those with low-MVD tumors, and the survival rate of those patients with VEGF-positive tumors was significantly poorer than in those with VEGF-negative tumors (P = 0.009 and P = 0.04, respectively). The cumulative survival rates in the VEGF-positive groups were found to be significantly poorer in the pT3 and pathological node (pN)1 groups when stratified according to pT factor (pathological T category) and pN factor (pathological N category) in the tumor-node-metastasis (TNM) classification. VEGF expression had the second highest hazard ratio in the multivariate analysis, after pN factor. These results indicate that VEGF is a useful marker for predicting the outcome in patients with more advanced esophageal squamous cell carcinoma. It seems that TNM factors and VEGF expression are important factors in the selection of appropriate treatments.

Adult↗
PubMed2000

A case of aortoduodenal fistula occurring after surgery and radiation for pancreatic cancer.

The patient was a 58-year-old woman given curative treatment (pancreatectomy (body and tail) + intraoperative irradiation (25 Gy)) on the basis of a diagnosis of pancreatic carcinoma. Having a favorable postoperative course, she was discharged 24 days after surgery. A week after discharge, she was readmitted for a hemorrhagic gastric ulcer. She was later discharged again on conservative treatment, and followed up at the outpatient clinic, but nine months postoperatively, was readmitted complaining of loss of appetite and abdominal pain. Subsequent tests revealed stricture of the horizontal portion of the duodenum with distension oral to the stricture. Around the celiac artery, the paraaortic lymph nodes were swollen, and a diagnosis of stricture due to recurrent pancreatic carcinoma was made. On the day before bypass surgery was scheduled, the patient vomited blood, so the operation was postponed, conservative treatment such as blood transfusion was administered, and emergency angiography was performed simultaneously. The findings were an aortic pseudoaneurym 1 cm in diameter immediately below the origin of the superior mesenteric artery and between the left and right renal arteries, and a hemorrhage, caused by an aortoduodenal fistula, issuing from the horizontal portion of the duodenum. Hemostasis via a laparotomy was judged difficult, and so an indwelling stent-graft in the aorta was tried to stanch the blood, but without success. Another stent then had to be inserted within the first, thus stopping the flow, but the blood supply to the celiac artery, the superior mesenteric arteries and the renal arteries was impaired, and the patient died about six hours later. Postmortem examination revealed aortoduodenal fistula without recurrence of the carcinoma. The duodenal wall around the fistulous tract showed delayed radiation changes with deep ulceration. The intraoperative radiation may have played an important part in the formation of the fistula.

Aortic Diseases↗