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K Sugimachi

Publications and source records attributed to K Sugimachi.

At least 217 records · Page 12Linked to original sources
PubMed1999

The p53 tumor suppressor gene in anticancer agent-induced apoptosis and chemosensitivity of human gastrointestinal cancer cell lines.

PURPOSE: While the target of many anticancer agents has been identified, the processes leading to killing of the cancer cells and the molecular basis of resistance to the drugs are not well understood. We used human gastrointestinal cancer cell lines and examined how anticancer agents induced cell killing and how the chemosensitivity of these lines was determined. METHODS: Twelve gastrointestinal cancer cell lines were examined for the presence of either a wild-type or mutant p53 gene by direct sequencing. We also determined whether or not cell killing would occur when the cell lines were exposed to anticancer drugs. The sensitivity to the anticancer agents was determined based on colony formation. RESULTS: All 12 gastrointestinal cancer cell lines carried either a wild-type or mutant p53 gene. Three lines, MKN45, MKN74 and COLO320, carried the wild-type p53 gene, and nine carried the mutant p53 gene. When three lines were exposed to the anticancer agents etoposide, doxorubicin (DXR) or 5-fluorouracil (5-FU), cell death ensued. In these cells, the population of cells in G1 phase increased after exposure to high-dose anticancer agents, but cells in G2 phase increased when exposed to low-dose anticancer agents. Our observations support the concept that cells carrying the wild-type p53 gene tend to be sensitive to etoposide and DXR and, in particular, deletion of the p53 function results in a greater resistance to anticancer agents. CONCLUSION: Based on our findings, human gastrointestinal cancer-related cell death apparently occurs via a p53-dependent pathway. A relationship was observed between the induction of cell death and chemosensitivity.

Antineoplastic Agents↗
PubMed1999

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Journal Article↗
PubMed1999

Transanal endoscopic microsurgery for T1 rectal cancer in patients with synchronous colorectal cancer.

We treated T1 rectal cancer in three patients with synchronous colorectal cancer by transanal endoscopic microsurgery (TEM) before performing a radical operation for the second lesion. On pathological examination, all rectal specimens resected by TEM showed cancer invasion within the submucosal layer, while the margins of the specimen were completely free of cancerous tissue. Few complications were encountered with either the TEM for the rectal lesions or the succeeding radical operation for the second lesions. When patients present with synchronous colorectal cancer, including T1 rectal cancer, local excision of the rectal lesion via TEM can help to improve the patient's quality of life without affecting the curability of the disease.

Aged↗
PubMed1999

Results of laparoscopic splenectomy for immune thrombocytopenic purpura.

BACKGROUND: Laparoscopic splenectomy has been demonstrated to be technically feasible and safe for the treatment of immune thrombocytopenic purpura (ITP), hereditary spherocytosis, and Hodgkin's disease. PATIENTS AND METHODS: The study comprised 76 consecutive patients with chronic ITP who were admitted to our hospital from 1968 to 1997 and underwent splenectomy; 35 patients underwent a laparoscopic splenectomy, and 41 had open surgery. RESULTS: Laparoscopic splenectomy involved minimal incision, and a significantly lower frequency of analgesia was required for postoperative abdominal pain (1.4 versus 3.3); postoperative hospital stay was shorter (9.6 versus 20.1 days, P <0.05). Operative time was significantly longer for the laparoscopic surgery (204.5 versus 99.8 minutes, P <0.01), but blood loss was less (154.4 versus 511.7 g, P <0.01). During the present study (range 3.8 to 80 months), accumulative nonrecurrence rate was 67.9% in 5 years after surgery, which is similar to that of the previous open splenectomy. CONCLUSIONS: Laparoscopic splenectomy can become an alternative therapeutic modality in the treatment of ITP.

Adult↗
PubMed1999

Rare occurrence of colorectal cancer metastasis in livers infected with hepatitis B or C virus.

BACKGROUND: The rarity of the occurrence of metastatic malignancy in injured liver has been noted by many observers. However, since the clinicopathological features of primary carcinoma and the etiology of liver disease of these patients vary greatly, this phenomenon may not be universal. METHODS: We evaluated the relationship between either hepatitis B virus (HBV) or hepatitis C virus (HCV) infection and the incidence of colorectal liver metastasis in 438 patients undergoing surgical treatment for advanced colorectal carcinoma. RESULTS: The liver function of the patients in the infection group (n = 37) was significantly worse than that of those in the noninfection group (n = 401). The incidences of tumor recurrence in the lung or peritoneum were comparable between the two groups. However, the percentage of patients with liver metastases in the infection group (3 of 37, 8.1%) was significantly lower (P <0.05) than that of those in the noninfection group (85 of 401, 21.2%). The patients in the infection group tended to survive longer than the patients in the noninfection group. CONCLUSIONS: We herein report an initial finding that colorectal carcinoma rarely metastasizes to livers infected with HBV or HCV.

Aged↗
PubMed1999

Postoperative adjuvant adoptive immunotherapy with lymph node-LAK cells and IL-2 for pathologic stage I non-small cell lung cancer.

We conducted a clinical trial of adoptive immunotherapy with lymph node-lymphokine-activated killer (LN-LAK) cells and recombinant interleukin 2 (rIL-2) for a surgical adjuvant therapy of pathologic stage I non-small cell lung cancer. The regimen consisted of the subcutaneous administration of low-dose rIL-2 for 6 consecutive days and the transfer of ex vivo generated LAK cells from regional lymph node lymphocytes, obtained at the time of surgical operation. A group of 19 patients with primary lung cancer received the immunotherapy about 2 weeks after surgery (pulmonary lobectomy). The regimen was postoperatively well tolerated by the patients. In peripheral blood lymphocytes (PBL) obtained after the treatment, the proportion of CD3+ T cells predominantly increased with the increase of CD4+ T cell subsets. On the other hand, the proportion of CD20+ B cells decreased. Both NK and LAK activity of PBL significantly increased. However, the immunomodulatory effects did not result in a prolongation of the postoperative survival time in comparison to the postoperative survival of patients (n = 21) with surgery alone during the same period. These results suggested that the treatment with low-dose LN-LAK cells and concurrent low-dose IL-2 could, therefore, neither reduce nor eradicate minimal micrometastatic diseases.

Aged↗
PubMed1999

Postoperative liver failure after major hepatic resection for hepatocellular carcinoma in the modern era with special reference to remnant liver volume.

BACKGROUND: Postoperative liver failure is a life-threatening complication after hepatic resection. Because of recent advances in liver surgery technique and a more stringent patient selection, mortality after hepatic resection has steadily decreased, but its incidence still ranges from 10% to 20%. The factors linked to postoperative liver failure in major hepatic resection in the modern era should be reevaluated. STUDY DESIGN: Of 80 patients with viral markers (hepatitis C viral antibody or hepatitis B surface antigen) who underwent major hepatic resections (no less than bisegmentectomies) for hepatocellular carcinoma between 1990 and 1996, 7 patients (8.8%) died of postoperative liver failure within 6 months after hepatectomy. The cause of liver failure was analyzed based on both the preoperative data and the intraoperative findings. In addition, since all the patients who died of liver failure underwent a right hepatic lobectomy, a further data analysis was also done in 47 patients who underwent a right lobectomy of the liver. A volumetric analysis by CT was then done to evaluate the remnant liver volume. RESULTS: Between the patients with liver failure and those without liver failure who underwent a right lobectomy, there were no significant differences in preoperative data or intraoperative findings. Volumetric analysis revealed that the remnant liver volume of patients who died of liver failure was significantly smaller than that of patients who lived (p = 0.008). The incidence of liver failure in patients with a remnant liver volume of less than 250 mL/m2 was 7 of 20 (38%), while it was 0 of 27 in patients with a liver volume of no less than 250 mL/m2 (p = 0.0012). The only significant risk factor for liver failure in patients with a remnant liver volume of less than 250 mL/m2 was diabetes mellitus (p = 0.0072). CONCLUSIONS: The expected remnant liver volume appears to be a good predictor for liver failure in patients who undergo a right lobectomy of the liver. In patients with diabetes mellitus and an expected remnant liver volume of less than 250 mL/m2, a major hepatectomy should be avoided. Careful patient selection based on volumetric analysis in major hepatectomy cases could help prevent the occurrence of postoperative liver failure.

Aged↗
PubMed1999

Postoperative chemo-endocrine treatment with mitomycin C, tamoxifen, and UFT is effective for patients with premenopausal estrogen receptor-positive stage II breast cancer. Nishinihon Cooperative Study Group of Adjuvant Therapy for Breast Cancer.

The effectiveness of combining mitomycin C (MMC), tamoxifen (TAM), and 1-(2-tetrahydrofuryl)-5-fluorouracil (tegafur) was evident in patients with estrogen receptor-positive (ER+) breast cancers. UFT, an oral preparation of tegafur and uracil at a molar ratio of 1:4, was reported to have higher antitumor effects than tegafur alone for patients with breast cancer. Therefore, the combined chemotherapy of MMC, TAM and UFT may possibly be effective for breast cancer. From 1988 to 1991. we studied the effects of postoperative adjuvant therapy for Japanese women with stage 11 breast cancer, all seen at 71 institutions in western areas of Japan. Five hundred and ninety four patients with stage II primary breast cancer who had undergone curative surgery, including total mastectomy and axillary lymph node dissection, were enrolled. On the day of surgery, each patient was given 13 mg/m2 of MMC intravenously. Patients with ER+ tumors were then assigned to group A or group B. Group A received 30 mg/day of TAM given orally from postoperative 2 weeks, for 2 years. Group B was additionally given an oral dose of 300 mg/day of UFT for 2 years, given concomitantly with 30 mg/day of TAM. Patients with ER- tumors were assigned to group C or group D. Group C were prescribed 300 mg/day of UFT, orally, from postoperative 2 weeks for 2 years, and group D were additionally given an oral dose of 30 mg/day of TAM together with 300 mg/day of UFT. There were no differences among the groups regarding prognostic factors or doses of MMC and TAM in ER+ patients and MMC and UFT in ER- patients. Toxicity rates for leukopenia, anorexia, and nausea/vomiting were higher in group B than in group A patients. There were no statistical differences in the overall survival and disease-free survival times between groups A and B, or groups C and D, for all eligible cases. In a retrospective subgroup analysis using Bonferroni's adjustments, the additional effect of UFT on the combined treatment of MMC and TAM lengthened the disease-free survival time for patients with premenopausal ER+ cancers (corrected P value by Bonferroni's adjustments <0.05). Multivariate analysis showed that effects of the combined treatment of MMC, TAM, and UFT was significantly related to the menopausal status (P<0.01). Our findings show that postoperative ingestion of MMC, TAM, and UFT was effective for patients with premenopausal ER+ stage II breast cancer.

Adult↗
PubMed1999

Lack of DMBT1 expression in oesophageal, gastric and colon cancers.

Loss of sequences from human chromosome 10q has been reported in several different cancers. Recently, a second candidate tumour-suppressor gene, DMBT1, was identified in this chromosomal region. We studied the mRNA expression and homozygous deletion of this gene in human oesophageal, gastric and colon cancers. Reverse transcriptase polymerase chain reaction (RT-PCR) amplification demonstrated that 23 (53.5%) of 43 oesophageal, 5 (12.5%) of 40 gastric, and 4 (16.7%) of 24 colorectal cancer cases showed an apparent reduction in DMBT1 mRNA in tumour tissues compared with paired normal tissues. Twelve out of 15 oesophageal cancer cell lines also showed no expression. We next studied homozygous deletions within the DMBT1 gene in oesophageal cancers by using duplex PCR. Consequently, it was recognized in five (11.6%) of the primary tumours and two (13.3%) of the cell lines. These findings suggest that DMBT1 may act as a tumour-suppressor gene not only in brain tumours but also in gastrointestinal cancers, especially in oesophageal cancers.

Agglutinins↗
PubMed1999

Prognostic value of p53 protein expression for patients with gastric cancer--a multivariate analysis.

Mutations in the p53 gene, one of the most common genetic alterations in human cancer, are implicated in tumorigenesis and tumour progression. Although p53 protein expression appears to be correlated to prognosis in patients with malignancy, its prognostic role in gastric cancer has remained controversial. We examined the clinical significance of p53 overexpression in 427 patients with gastric cancer, using multivariate analysis. Tumour sections of gastric cancer tissues from these 427 Japanese patients were stained immunohistochemically with monoclonal antibody PAb1801. The presence of p53 expression was statistically compared with clinicopathological features and post-operative survival, using univariate and multivariate analyses. p53 expression was detected in 38.6% (165 out of 427) of these gastric cancers and immunoreactivity was not observed in normal mucosa adjacent to the tumour. A higher rate of p53 detection was observed among large tumours and in those with a prominent depth of invasion, lymphatic and vascular invasion and lymph node involvement. Prognosis was significantly worse for patients with p53-positive-staining tumours. The 5-year survival rate was 62.5% for patients with p53-negative tumours and 43.3% for those with positive malignancies. p53 expression was a significant prognostic factor for node-positive gastric cancers in subjects undergoing treatment with curative resection, as assessed by Cox regression analysis. Thus, the expression of p53 was closely related to the potential for tumour advance and a poorer post-operative prognosis for patients with gastric cancer.

Analysis of Variance↗
PubMed1999

Overexpression of metastasis-associated MTA1 mRNA in invasive oesophageal carcinomas.

The MTA1 gene is a recently identified novel candidate breast cancer metastasis-associated gene which has been implicated in the signal transduction or regulation of gene expression. We examined the mRNA expression levels of the MTA1, the human homologue of the rat mta1 gene in 47 surgically resected oesophageal squamous cell carcinomas by quantitative reverse transcription polymerase chain reaction. The relative overexpression of MTA1 mRNA (tumour/normal ratio > or = 2) was observed in 16 out of 47 (34.0%) oesophageal carcinomas. Oesophageal tumours overexpressing MTA1 mRNA (T/N ratio > or = 2) showed significantly higher frequencies of adventitial invasion (P < 0.05) and lymph node metastasis (P < 0.05), and tended to have a higher rate of lymphatic involvement than the remaining tumours. Thus, the data suggest that the MTA1 gene might play an important role in invasion and metastasis of oesophageal carcinomas.

Carcinoma, Squamous Cell↗
PubMed1999

Approach to withdrawal from tacrolimus in a fully allogeneic murine skin graft model.

With few exceptions, transplant patients must take immunosuppressants throughout their lives. In this study, we used anti-T-cell receptor (TCR/CD3) monoclonal antibodies (mAbs) to induce immunological tolerance to alloantigens after withdrawal from tacrolimus in a fully allogeneic murine skin graft model. Skin grafts from AKR donor mice were maintained in C57BL/6 recipients by administering tacrolimus for one month. Anti-T-cell receptor (TCR) alphabeta mAb was administered to recipient mice on the day of withdrawal from tacrolimus administration. Seven days after mAb administration, the recipient mice were treated with various combinations of the following treatments: low-dose whole body irradiation, AKR bone marrow transfer (BMT), and anti-CD3 mAb administration. The control recipient mice did not receive treatment with either mAb, nor any other treatment. All the control recipient mice showed rejection of AKR skin grafts 42 days after tacrolimus withdrawal (mean skin graft survival: 77 days). Mice treated with a combination of anti-TCR alphabeta antibody, low-dose irradiation and AKR BMT showed stable chimerism in their peripheral blood lymphocytes and significantly prolonged skin graft survival (mean skin graft survival: >151.2+/-15.3 days). Mice given the combination of anti-TCR alphabeta mAb, anti-CD3 mAb, low-dose irradiation, and AKR BMT exhibited more stable chimerism but had earlier skin graft rejection (mean skin graft survival: 116.7+/-17.6 days) than the mice that did not receive anti-CD3 mAb. These results suggest that anti-TCR alphabeta mAb, but not anti-CD3 mAb, in combination with low-dose irradiation and BMT, is useful for long-lasting allograft survival after withdrawal from tacrolimus in mice with fully allogeneic skin grafts.

Animals↗
PubMed1999

A selective cyclo-oxygenase-2 inhibitor, NS-398, may improve portal hypertension without inducing gastric mucosal injury.

BACKGROUND AND AIMS: Prostacyclin has been shown to play a role in hyperdynamic circulation in portal hypertension. Recently, a new subtype of cyclo-oxygenase (COX), COX-2, which acts as an inducible synthase in response to various stimuli. The aim of this study was to investigate whether COX-2 contributes to portal hypertension and whether a COX-2 blockade induces the same sort of gastric mucosal injury as a COX-1 blockade. METHODS: Portal hypertension (PHT) in rats was induced by a two-step ligation of the portal vein. The mean arterial pressure (MAP), portal pressure (PP), visceral blood flow volume (BFV), serum levels of 6-keto-prostaglandin F1alpha (PGF1alpha), thromboxane B2 (TXB2) and gastric mucosal injury induced by pure ethanol were all measured in PHT rats receiving different inhibitors (indomethacin, a highly selective COX-1 inhibitor; NS-398, a highly selective COX-2 inhibitor). Control rats treated by a sham operation were also studied. RESULTS: The NS-398 administration significantly decreased PP to the same extent as indomethacin at doses of 5 and 10 mg/kg in PHT rats after a 60 min administration, while neither inhibitor affected the control rats. Both inhibitors significantly increased PP after a 30 min administration in the PHT and control rats at a dose of 5 mg/kg while both inhibitors significantly decreased PP after 60 min administration only in the PHT rats. Portal vein ligation treatment induced a significant increase in PP and BFV of the portal vein, gastric mucosa, oesophageal mucosa and the serum levels of 6-keto-PGF1alpha and TXB2, while portal vein ligation treatment induced a significant decrease in BFV of the liver. Both blockades increased MAP and decreased PP and BFV in the splanchnic area and decreased the serum level of 6-keto-PGF1alpha and TXB2 in the PHT rats, while neither blockade modified any parameters in the control rats, except that indomethacin administration significantly decreased the BFV of the gastric mucosa. Indomethacin administration significantly increased the ulcer index (UI). The NS-398 had no effect on UI in either the PHT or control rats. Only indomethacin significantly increased the number of rats demonstrating gastric mucosal long lesions (> 2 cm) in the PHT rats. CONCLUSION: In the PHT rats, prostaglandin seemed to contribute to portal hypertension. Both COX blockades reduced PP and BFV of the portal vein and gastric mucosa. NS-398, a selective COX-2 inhibitor, may, therefore, improve portal hypertension without inducing gastric mucosal injury.

6-Ketoprostaglandin F1 alpha↗
PubMed1999

Properties of endothelium and smooth muscle cells in canine femoral arteries after lumbar sympathectomy.

OBJECTIVE: To find out whether the lumbar sympathectomy modulated the endothelial function (as measured by nitric oxide (NO) and prostacyclin (PGI2), and blood flow in the canine femoral artery. DESIGN: Laboratory experiments. SETTING: Teaching hospital, Japan. ANIMALS: 16 mongrel dogs. INTERVENTION: Unilateral sympathectomy from L3 to L6. MAIN OUTCOME MEASURES: Five weeks later, the changes in blood flow, the endothelium-dependent responses and the PGI2 production in the canine femoral arteries were measured. RESULTS: The median (range) blood flow of left (denervated) and right (innervated) femoral arteries was 162 ml/min (122-330) and 65 ml/min (40-92), respectively. There was a significant difference between the two groups (p < 0.01). The endothelium-dependent relaxations to acetylcholine, adenosine diphosphate (ADP) and A23187 were comparable. The amounts of PGI2 produced in the two groups were similar. Direct relaxation in response to sodium nitroprusside was also similar in the two groups. CONCLUSIONS: Lumbar sympathectomy did not alter the endothelial function, although the median blood flow in the denervated femoral arteries was significantly higher than in the innervated ones. The continuous vasodilatation after sympathectomy may be a more potent factor in the regulation of vascular tonus than the physiological regulation of NO and PGI2.

Animals↗
PubMed1999

Expression and differential intracellular localization of two major forms of human 8-oxoguanine DNA glycosylase encoded by alternatively spliced OGG1 mRNAs.

We identified seven alternatively spliced forms of human 8-oxoguanine DNA glycosylase (OGG1) mRNAs, classified into two types based on their last exons (type 1 with exon 7: 1a and 1b; type 2 with exon 8: 2a to 2e). Types 1a and 2a mRNAs are major in human tissues. Seven mRNAs are expected to encode different polypeptides (OGG1-1a to 2e) that share their N terminus with the common mitochondrial targeting signal, and each possesses a unique C terminus. A 36-kDa polypeptide, corresponding to OGG1-1a recognized only by antibodies against the region containing helix-hairpin-helix-PVD motif, was copurified from the nuclear extract with an activity introducing a nick into DNA containing 8-oxoguanine. A 40-kDa polypeptide corresponding to a processed form of OGG1-2a was detected in their mitochondria using antibodies against its C terminus. Electron microscopic immunocytochemistry and subfractionation of the mitochondria revealed that OGG1-2a locates on the inner membrane of mitochondria. Deletion mutant analyses revealed that the unique C terminus of OGG1-2a and its mitochondrial targeting signal are essential for mitochondrial localization and that nuclear localization of OGG1-1a depends on the NLS at its C terminus.

Alternative Splicing↗
PubMed1999

The significance of stromal desmoplasia in intrahepatic cholangiocarcinoma: a special reference of 'scirrhous-type' and 'nonscirrhous-type' growth.

Fifty-eight surgically resected cases of intrahepatic cholangiocarcinoma (ICC) were examined grossly and microscopically. We microscopically categorized the ICC into two groups, "scirrhous-type" ICC (SICC) and "nonscirrhous-type" ICC (NSICC), according to the degree of the stromal desmoplasia in the tumor. We next assessed the histologic characteristics including proliferative activities and prognoses. Additionally, the prognostic factors of ICC were examined by univariate and multivariate analyses. Histologically, the incidences of lymphatic permeation and perineural invasion in SICC (85.7% and 100.0%, respectively) were significantly higher than those in NSICC (47.7% and 45.6%, respectively). The mean MIB-1 labeling index of SICC (mean+/-standard deviation, 29.9%+/-14.3%) was significantly higher than that of NSICC (mean+/-standard deviation, 19.1%+/-14.3%). Additionally, the 1- and 3-year survival rates of the SICC were 64.3% and 22.0%, respectively, and those of NSICC were 72.8% and 55.8%, respectively. The survival rate of SICC was significantly lower than that of NSICC. Overall, lymphatic permeation, intrahepatic metastasis, and lymph node metastasis were all considered to be independent prognostic factors for a worse prognosis based on the multivariate analyses, whereas our new category based on stromal desmoplasia or other variables were not. Our study thus indicates that lymphatic permeation, perineural invasion, and a higher proliferative activity of tumor cells carry a poorer prognosis in SICCs than in NSICCs. Although the overall independent prognostic factors were lymphatic permeation, intrahepatic permeation, and lymph node metastasis based on a multivariate analysis, a detailed histologic examination related to the stromal desmoplasia in the tumor is also considered to be useful for evaluating the biologic behavior of the ICC.

Adult↗