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Biomedical subjects

K Sugimachi

Publications and source records attributed to K Sugimachi.

At least 307 records · Page 17Linked to original sources
PubMed1998

Expression of insulin-like growth factor 2 mRNA in human gastric cancer.

Insulin-like growth factor 2 (IGF2) stimulates cell proliferation and development in normal human growth. In several human cancers, the IGF2 gene is overexpressed and is thus considered to be a growth factor for tumors mediated through both the paracrine and autocrine pathways. However, the significance of IGF2 mRNA expression in gastric cancer has yet to be clarified. We semi-quantitatively measured the expression of IGF2 mRNA in 57 Japanese cases of gastric cancer by means of the reverse transcription polymerase chain reaction and also analyzed the relation between the IGF2 expression status and other clinicopathologic factors. We also performed immunohistochemical staining for IGF2. In 41 of 57 cases (72%), the expression of IGF2 mRNA was greater in tumor tissue (T) than in normal tissue (N). The average tumor/normal (T/N) expression ratio of IGF2 mRNA corrected for that of control gene mRNA was 1.42, while ranging from 0.36 to 3.65. The T/N ratio of infiltrative-type cancers was greater than that of expanding-type cancers (p<0.05). The cases with lymphatic permeation showed a greater T/N ratio than those without lymphatic permeation in expanding-type cancers (p<0. 05). Immunohistochemical staining revealed IGF2 to be detected in cancer cells themselves, especially at the margin of the cancer tissue. The IGF2 gene may thus play an important role in lymph vessel permeation especially in expanding-type gastric cancers.

Gene Expression↗
PubMed1998

Treatment of advanced gastric cancer with 5-fluorouracil and cisplatin in combination with dipyridamole.

We investigated the efficacy of combination chemo-therapy using 5-fluorouracil (5-FU), cisplatin (CDDP), and dipyridamole (DP), which is based on the concept of double biochemical modulation. Twenty-eight patients with advanced gastric cancer were treated with the simultaneous continuous intravenous (i.v.) infusion of 5-FU (800 mg/m2/day) and DP (4 mg/kg/day), and i.v. infusion of CDDP (20 mg/m2/day) for 5 days. The cycles were repeated every 4 weeks. Twelve patients (43%) had a partial response (PR), while stable disease (NC) occurred in 13 patients (46%), and progression (PD) in 3 patients (11%). An improved performance status was observed in 20 patients (71%). The carcinoembryonic antigen (CEA) level was markedly decreased in 75% of the CEA-positive patients. Toxicity was acceptable. The mean steady state plasma concentration of total DP was 6.40.5 microM, which thus seemed adequate to potentiate the cytotoxicity of 5-FU. The treatment regimen described herein thus appears to be effective, safe and well tolerated by patients with advanced gastric cancer.

Adult↗
PubMed1998

Effect of thromboxane synthetase inhibitor on non-heart-beating donors in rat orthotopic liver transplantation.

BACKGROUND: The use of non-heart-beating donors could relieve donor organ shortage provided that the outcome of the recipients is not jeopardized. METHODS: In this study we evaluated the effect of thromboxane synthetase inhibitor (OKY-046) on non-heart-beating donors in orthotopic liver transplantation in rodents. OKY-046 (OKY group, n = 8) or vehicle (control group, n = 8) was given to the donor animals for 60 minutes before the induction of 30 minutes of warm ischemia to the liver before transplantation and survival, and several parameters were compared between the two groups. RESULTS: All recipients in the control group died within 2 days, whereas 67% of those of the OKY group had a 2-day survival and 44% had a 2-week survival (p < 0.01). Bile output from the allograft for 2 hours after reperfusion was significantly larger in the OKY group at all time points (p < 0.05). Furthermore, serum transaminase levels 10 minutes after reperfusion were significantly lower in the OKY group (p < 0.05), although those 120 minutes after reperfusion were comparable between the two groups. The thromboxane B2 level in liver tissue 10 and 120 minutes after reperfusion was significantly lower in the OKY group compared with the control group (p < 0.02 and p < 0.05, respectively). CONCLUSIONS: These results indicate that OKY-046 given to the donor before the induction of warm ischemia could ameliorate ischemia/reperfusion injury of the hepatic allograft by reducing thromboxane A2 production after reperfusion.

Alanine Transaminase↗
PubMed1998

[Possible role of cytomegalovirus infection in the pathogenesis of human vascular diseases].

In order to evaluate the pathogenic role of human cytomegalovirus(CMV) infection in human vascular disease, we first examined the role of CMV immediate early gene (CMV-IE) expression in vascular smooth muscle cell (VSMC) proliferation. The in vitro IE gene transfer stimulated VSMC proliferation. The in vivo IE gene transfer showed neointimal thickening while the control arteries did not. In the wall of "so-called" inflammatory abdominal aortic aneurysm (IAAA), CMV infected cells were more frequently encountered than in that of AA and control cases. CMV infected cells were largely identified as macrophages or fibroblasts, and these cells frequently expressed CMV-IE gene. These findings thus suggest that the persistent expression of CMV-IE gene in the vessel wall may play a role in the vascular cellular responses, including progression of atherosclerosis or vasculitis, in vivo.

Animals↗
PubMed1998

Gastric carcinoma with pyloric stenosis.

BACKGROUND: The surgical outcome of gastric carcinomas with pyloric stenosis and their prognostic factors are sparsely documented. METHODS: A clinicopathologic study of gastric carcinoma with pyloric stenosis (PS group, n = 122) was done and findings were compared with the cases involving the antrum (A group, n = 695). Independent prognostic factors for survival of the patients with PS were determined by Cox's proportional hazard model. RESULTS: There were no differences in age and gender between the two groups. The PS group was characterized by an infiltrating growth pattern and undifferentiated adenocarcinoma. The incidence of serosal invasion, direct invasion into neighboring organs, peritoneal dissemination, lymph node metastasis, and liver metastasis of the PS group was higher than those of the A group (p < 0.01). The resection rate and 5-year survival of the PS group were 78% and 22%, respectively; these values were significantly lower than 98% and 58% of the A group (p < 0.01). Multivariate analyses showed that operative curability, resection of the stomach, liver metastasis, serosal invasion, and histologic type were the independent prognostic factors of the PS group. CONCLUSIONS: In cases of gastric carcinoma with pyloric stenosis, efforts should be made to do a curative operation, but for other patients with poor prognostic factors, intensive surgery and adjuvant therapy should be considered.

Aged↗
PubMed1998

Laparoscopic repair for perforation of duodenal ulcer with omental patch: report of initial six cases.

We report our initial experience with perforated duodenal ulcer treated by laparoscopic repair with omental patch in six patients, and the results are compared with those of other procedures retrospectively. The average operative time was 85.0 min, and the estimated blood loss was 13.7 ml. The estimated blood loss of laparoscopic repair was significantly less than that of gastrectomy (p < 0.01). However, although all patients with gastrectomy or open omental patch needed administration of analgesia, only half of patients require analgesia in laparoscopic repair. No postoperative complication was encountered, and the recurrence of ulcer was not recognized in a mean follow-up of 10 months. We recognized this procedure to be safe and feasible. Although a larger number of patients with longer follow-up is needed, this procedure may become one of the treatments for perforated duodenal ulcer.

Adult↗
PubMed1998

[A new microsatellite instability analysis using fluorescent primers and laser scanning].

To demonstrate the instability of microsatellite sequences, which have been linked to DNA mismatch repair deficiency and indicate a high risk of carcinogenesis, polymerase chain reaction (PCR) and electrophoretic analysis have been used. However, the electrophoretic profiles of PCR-amplified microsatellite sequences are often too complicated, and the conventional method using autoradiography has critical problems in detection characteristics and migration accuracy. First, we made use of fluorescence-labeled PCR and laser scanning to detect bands quantitatively. Second, we characterized Taq polymerase-dependent modification of the amplified microsatellite sequences and optimized the electrophoretic profiles by enzymatic modification with T4 DNA polymerase. Third, we developed a dual fluorescence co-electrophoresis system, in which both samples derived from cancer and normal tissues are electrophoresed in the same lane, in order to minimize migration errors. Furthermore, we classified all of the observed patterns of microsatellite alteration and set up new criteria for assessing microsatellite instability. Using the system developed here and the criteria we proposed, a precise judgment can be made and rates of positivity in various human malignancies may be corrected.

DNA-Directed DNA Polymerase↗
PubMed1998

Expression spectrum of melanoma antigen-encoding gene family members in colorectal carcinoma.

OBJECTIVE: The 12 members of the human melanoma antigen-encoding (MAGE) gene family encode tumor-specific peptide antigens. Some antigens coded by the MAGE genes are potentially useful for cancer-specific immunotherapy. However, little information on the expression of these genes in human colon carcinomas is available. We investigated the expression of 10 of the 12 genes in human colon tissue. DESIGN: Eighty pairs of tumor and normal tissue samples from the human colon were studied by means of reverse transcription-polymerase chain reaction. RESULTS: None of the genes was expressed in the 80 control samples of normal tissue. On the other hand, expression was recognized in tumor samples, ranging from 5% of samples for MAGE-6 to 44% for MAGE-8. Seventy of the 80 tumor samples (88%) expressed at least 1 of the 10 MAGE genes. The frequency of liver metastasis was significantly higher in cases with tumor samples that expressed MAGE-3 than in those that did not express this gene. This tendency was not observed for other members of the MAGE gene family. No significant differences were observed in the other clinicopathologic factors between any MAGE-positive and -negative tumor cases. CONCLUSIONS: The MAGE genes were exclusively expressed in carcinoma tissues and not in normal tissues of the colon. The finding that nearly 90% of tumors expressed at least one MAGE gene indicates the possible clinical use of this gene for both immunotherapy and molecular diagnosis.

Antigens, Neoplasm↗
PubMed1998

Expression of adrenomedullin in portal hypertensive gastric mucosa of rats.

We examined the expression and localization of adrenomedullin (AM) mRNA, AM receptor (AM-R) mRNA and AM protein in normal and portal hypertensive (PHT) rat gastric mucosa. Methods included competitive reverse transcription-polymerase chain reaction (RT/PCR), in situ hybridization and Western blot analysis. Both AM mRNA and AM-R mRNA were strongly expressed not only in normal rat gastric mucosa but also PHT rat gastric mucosa. While total AM and AM-R mRNA abundance was similar in both normal and PHT stomachs, in the superficial mucosa-where major defense mechanisms are located-their expression was significantly reduced in PHT rats by 33% (AM mRNA) and 25% (AM-R mRNA) (both p .0.05). AM protein was also expressed similarly in both normal and PHT gastric mucosa. We conclude that AM and its receptor play a role in regulation of gastric mucosal microcirculation and thus gastric mucosal defense.

Adrenomedullin↗
PubMed1998

Transaxillary approach for the endoscopic extirpation of benign breast tumors.

Cosmetic factors in the treatment of breast disease have long been neglected despite the fact that patients are highly concerned about the length and extent of the incision. Recent developments in both endoscopy and endoscopic devices have now made it possible to reach breast mass(es) from small incisions in the axilla. We describe the successful extirpation of a giant fibroadenoma of the breast in a 20-year-old woman, using a 3-mm or 10-mm endoscope and a 3-mm or 5-mm endoscopic device with a transaxillary approach. A scar-free breast with an excellent cosmetic result was achieved by use of this technique and these devices. Benign tumors (both single large tumors and multiple masses) are therefore considered to be ideal candidates for this type of minimally invasive endoscopic surgery.

Adult↗
PubMed1998

Tumor angiogenesis and micrometastasis in bone marrow of patients with early gastric cancer.

In a subset of patients with early gastric cancer, there were recurrences of the disease after a curative resection had been done. Direct evidence of tumor seeding in distant organs at the time of surgery for gastric cancer is not available. An immunocytochemical assay for epithelial cytokeratin protein may fill this gap because it is a feature of epithelial cells that would not normally be present in bone marrow. From 1994-1997, the bone marrow of 45 patients with early gastric cancer was examined for tumor cells, using immunocytochemical techniques and an antibody reacting with cytokeratin, a component of the intracytoplasmic network of intermediate filaments. Intratumoral microvessels were stained with anti-CD31 monoclonal antibody. Clinicopathological characteristics were determined for subjects with cytokeratin-positive cells in the bone marrow. Of these 45 patients, 9 (20.0%) had cytokeratin-positive cells in the bone marrow at the time of primary surgery. These positive findings were not related to tumor advance-related factors of lymph node metastasis and distinct lymphatic and vascular invasion. Microvessel density in the primary tumor exceeded 2-fold in cytokeratin-positive cells, compared with findings in negative cells (P < 0.05). Tumor cells in bone marrow are indicative of the general disseminative metastasis in patients with early gastric cancer, and the metastatic potential was closely related to angiogenesis in the primary tumor.

Aged↗
PubMed1997

Precise assessment of microsatellite instability using high resolution fluorescent microsatellite analysis.

The instability of microsatellite sequences dispersed in the genome has been linked to a deficiency in cellular mismatch repair. This phenotype has been frequently observed in various human neoplasms and is regarded as a major factor in tumorigenesis. To demonstrate alterations in microsatellite sequences, polymerase chain reaction (PCR) and electrophoretic analysis are techniques often used. However, the electrophoretic profiles of PCR-amplified microsatellite sequences have not been well characterized. Moreover, the conventional method using autoradiography has critical problems in detection characteristics and migration accuracy. We made use of fluorescence-labeled PCR and laser scanning with linear detection characteristics, so as to detect bands quantitatively. Next, we characterized Taq polymerase-dependent modification of the amplified microsatellite sequences, using artificially synthesized microsatellite alleles and we optimized the electrophoretic profiles by enzymatic modification with T4 DNA polymerase. We developed a dual fluorescence co-electrophoresis system, in which both samples derived from cancer and normal tissues are electrophoresed in the same lane, in order to minimize migration errors. These improvements remarkably facilitate precise and objective assessments of microsatellite instability. Analyzing many positive cases in cell lines and tissue specimens, we classified all the patterns of microsatellite alteration and set up new criteria for assessing microsatellite instability.

Adenocarcinoma↗
PubMed1997

Overexpression of the MTA1 gene in gastrointestinal carcinomas: correlation with invasion and metastasis.

The mta1 gene is a recently identified novel candidate metastasis-associated gene. The deduced amino acid sequence contains an src homology-3 domain binding motif, a zinc finger motif and possible phosphorylation sites, suggesting that this gene is involved in signal transduction or regulation of gene expression. The purpose of our study was to examine the mRNA expression levels of the MTA1, the human homologue of the rat mta1 gene in colorectal and gastric carcinomas and thus to evaluate the relevance of the expression of this gene to human carcinoma progression. The expression of MTA1 mRNA in 36 colorectal and 34 gastric carcinoma samples was compared with that in corresponding normal mucosa tissues by semi-quantitative reverse-transcription polymerase chain reaction (RT-PCR) and the results were compared with clinico-pathologic data. A relative overexpression of MTA1 mRNA (tumor/normal ratio > or = 2) was observed in 14 of 36 (38.9%) colorectal carcinomas and 13 of 34 (38.2%) gastric carcinomas. Clinico-pathologic correlations demonstrated that in colorectal carcinomas, tumors overexpressing MTA1 mRNA exhibited a significantly deeper wall invasion and a higher rate of metastasis to lymph nodes, and tended to be at an advanced Dukes' stage with frequent lymphatic involvement. In gastric carcinomas, the tumors overexpressing MTA1 mRNA showed significantly higher rates of serosal invasion and lymph node metastasis and tended to have a higher rate of vascular involvement. Our data suggest that overexpression of the MTA1 gene correlates with tumor invasion and the presence of metastases and that a high expression of MTA1 mRNA may be a potential indicator for assessing the malignant potential of colorectal and gastric carcinomas.

Aged↗
PubMed1997

New nortriterpenoid isolated from anti-rheumatoid arthritic plant, Tripterygium wilfordii, modulates tumor growth and neovascularization.

Preparations of Tripterygium wilfordii, "Thunder God vine", have been used in China to treat rheumatoid arthritis. Rheumatoid arthritis, as well as solid tumors, is closely associated with neovascularization. Antiarthritic drugs therefore may modulate tumor growth as well as neovascularization. We found that a compound purified from T. wilfordii, the nortriterpenoid, demethylzeylasteral (TZ-93), inhibited the proliferation of vascular endothelial cells approximately 30 times more effectively than it did for the proliferation of human tumor cells. In in vitro assays using bovine aortic endothelial cells, TZ-93 at non-toxic doses inhibited cell migration, expression of urokinase-type plasminogen activator (uPA) mRNA and uPA activity. Exogenous addition of uPA restored the inhibitory effect of TZ-93 on cell migration. In dorsal air-sac assays in BALB/c mice, the oral administration of 3 mg/kg/day TZ-93 for 5 days partially inhibited, and 30 mg/kg/day almost completely abrogated, the development of capillary networks induced by human hepatoblastoma cells. Similarly, 0.3 mg/kg/day TZ-93 partially inhibited, and 3 or 30 mg/kg/day almost completely blocked, the growth of mouse B16-F10 melanoma cells in a tumor implantation assay. The highest dose of TZ-93 significantly reduced the growth of well-vascularized tumors with volumes of more than 500 mm3. TZ-93 treatment of tumor-bearing mice significantly decreased the density of microvessels in the tumors. We conclude that TZ-93 may be useful in treating highly vascularized and metastatic tumors as well as other angiogenic diseases.

Animals↗
PubMed1997

Adenosquamous carcinoma of the liver: clinicopathologic characteristics and cytokeratin profile.

BACKGROUND: The clinicopathologic characteristics, biologic behavior, and histogenesis of primary adenosquamous carcinoma (ASC) of the liver have yet to be fully clarified. METHODS: Eight cases of ASC of the liver were analyzed both clinicopathologically and immunohistochemically using antibodies of cytokeratin (CK) 7, CK 8, CK 18, CK 19, and CK 903 (CK 5, CK 10, CK 11, and CK 14). The survival curve of the 6 patients with surgically resected ASC was compared with that of the 32 patients with common cholangiocarcinoma (CC). RESULTS: Most ASCs had invasive pathologic features, including venous invasion, lymphatic permeation, and intrahepatic metastases. There were lymph node metastases from 7 tumors (88%), and most of the metastases were adenocarcinoma. All adenocarcinoma (AC) components were positive for both CK 7 and CK 19. The squamous cell carcinoma (SCC) components were positive for CK 7 in all cases but were positive for CK 19 in only 5 cases (62.5%). The ACs were positive for CK 903 in only 3 cases (37.5%), whereas all SCCs were positive for CK 903. Almost all ACs were positive for both CK 8 and CK 18, whereas the SCCs were positive for CK 8 in only 3 cases (37.5%) and for CK 18 in no cases. All 6 patients with surgically resected ASC died of the disease within 1 year postoperatively. Their survival curve was significantly worse than that of the 32 patients with common CC (P < 0.001). The two patients on whom autopsy was performed also died within 1 year after diagnosis. CONCLUSIONS: ASC tended to have more aggressive biologic behavior and a poorer prognosis than common CC. The authors' immunohistochemical analysis of CK expression indicated that most of the ASCs of the liver that were studied developed from a squamous transformation of the preexisting CC.

Aged↗
PubMed1997

Meta-Analysis of the Second Collaborative Study of Adjuvant Chemoendocrine Therapy for Breast Cancer (ACETBC) in Patients with Stage II, Estrogen-Receptor-Positive Breast Cancer.

The second 5-year study of postoperative adjuvant therapy in patients with breast cancer between 1985 and 1988 was performed by the Study Group for Adjuvant Chemoendocrine Therapy for Breast Canecr (ACETBC). This report describes the results of a meta-analysis of the outcome. A total of 3012 patients with stage II, estrogen-receptor-positive primary breast cancer who underwent radical surgery (total mastectomy with at least axillary dissection) were eligible for the analyses. On the day of surgery, all patients received 13 mg/m(2) of mitomycin C (MMC) intravenously. Patients were then given one of two adjuvant chemoendocrine therapies for 2 years:regimen A, consisting of tamoxifen citrate (TAM) 30 mg/day, or regimen B, consisting of TAM 30 mg/day plus tegafur (Futraful, FT)600 mg/day. The results from all eligible patients were included in a meta-analysis according to the method of Peto et al. The odds reduction rate was 12 +/-13% (log-rank test, P= 0.35)for the 5-year survival rate and 16 +/- 10% (log-rank test, P=0.093)for the 5-year non-recurrence rate. In terms of the 5-year non-recurrence rate. regimen B(with FT)yielded slightly, but not significantly, better results than regimen A. In addition, stratified analyses were carried out with respect to the 5-year non-recurrence rate. Regimen B(with FT)yielded significantly better results than regimen A in patients with four or more positive axillary nodes (log-rank test, P= 0.039) and yielded slightly, but not significantly, better results than regimen A in premenopausal patients (log-rank test, P= 0.079).

Journal Article↗