Search PubMed⌕ Search

Biomedical subjects

K Sugimachi

Publications and source records attributed to K Sugimachi.

At least 325 records · Page 18Linked to original sources

Efficacy of Post-operative Adjuvant Therapy for Stage IIIa Berast Cancer: Futraful vs Futraful+Tamoxifen for ER-positive Patients and Futraful vs Futraful+Adriamycin for ER-negative Breast Cancer.

A multi-center, randomized controlled collaborative study was conducted in 310 institutions located thruoughout Japan for 3 years and 9 months from February 1985 until October 1988 to evaluate the efficacy of post-operative adjuvant therapy for patients who had previously undergone curative surgery for treatment of Stage III a breast cancer. Patients with estrogen receptor-positive [ ER(+)] breast cancer were treated with two types of regimens, ie, cyclophosphamide+adriamycin+fluorouracil (CAF; 2 cycles) +Futraful(FT) or CAF (2 cycles+FT+tamoxifen (TAM), and the clinical benefit of additional use of TAM was evaluated. Of the 509 ER(+) patients registered for the trial, 473 patients (92.9%) were eligible for evaluation.The 5-year survival rate was 77.2% for the CAF+FT group and 74.6% for the CAF+FT+TAM group, and the 5-year disease-free survival rate was 56.7% for the CAF+FT group and 59.2% for the CAF+FT+TAM group. Neither the survival rate nor the disease-free survival rate differed significantly between the groups. Analyses by factor revealed that the 5-year disease-free rate for lymph node-negative patients in the CAF+FT+TAM group was significantly higher than that for the corresponding patients in the CAF+FT group. No differences were noted in the incidence of adverse reactions between the two treatment groups, other than an increase in LDH (the frequency of which was higher in the CAF+FT+TAM group than in the CAF+FT group). Patients with estrogen receptor-negative [ ER(-)]breast cancer were treated with two types of regimens, ie, CAF+FT or CAF+FT+adriamycin(ADR), and the clinical benefit of the combined use of intermittent doses of ADR was evaluated. Of the 514 ER(-) patients registered in the trial, 478(93.0%) were eligible for evaluation. The 5-year survival rate was 64.9% for the CAF+FT group and 63.0% for the CAF+FT+ADR group, and the 5-year disease-free survival rate was 59.2% for both CAF+FT and CAF+FT+ADR groups. Neither the survival rate nor the disease-free survival rate differed significantly between the groups. There were no significant differences between these groups in analyses by nodal or menopausal status. The incidences of adverse reactions including anorexia, nausea/vomiting and alopecia were higher in the CAF+FT+ADR group than in the CAF+FT group.

Journal Article↗

Lymph node metastasis and relation to tumor growth potential and local immune response in advanced gastric cancer.

To evaluate the relation between the degree of lymph node metastasis and the growth potential of tumour cells and the local immune function in gastric cancer, we analyzed data on 444 patients with advanced serosally invasive gastric cancer who underwent curative gastrectomy. Tumour growth potential was evaluated based on the value proliferating cell nuclear antigen (PCNA) in the primary tumour, and dendritic cell infiltration into the tumour was determined as an indicator of local immune function. The values of PCNA labeling in the primary tumour increased and the infiltration of dendritic cells into the tumour decreased in relation to the extent of lymph node metastasis. High growth potential and low immune function were seen in cases with n3 lymph node metastasis. There was a reverse relation between the PCNA labeling index and dendritic cell infiltration. A variety of forms of recurrence was noted in patients with lymph node metastasis while the prognosis was less favorable, in relation to the degree of lymph node metastasis. Thus, the potential for nodal spread appears to be associated with the growth potential of tumour cells and with the local immune status of the tumour.

Cell Count↗

The anti-human tumor effect and generation of human cytotoxic T cells in SCID mice given human peripheral blood lymphocytes by the in vivo transfer of the Interleukin-6 gene using adenovirus vector.

Interleukin-6 (IL-6) was found to function as a late-acting killer helper factor in the differentiation of CTLs. In the model of tumor-bearing mice, the systemic administration of recombinant IL-6 was found to mediate the antitumor effect on the immunogenic murine tumors via the in vivo induction of murine CTLs but not on the poorly immunogenic murine tumors in our previous study. However, an in vivo experimental model capable of analyzing the anti-human tumor effect via the in vivo induction of human CTLs has not yet been established. Therefore, in the present study, severe combined immunodeficient mice were given human peripheral blood lymphocytes (SCID-PBL/hu), and thereafter human tumor cells were administered i.p. into these SCID-PBL/hu mice as a model of human patients with cancer. When these SCID-PBL/hu mice bearing allogeneic human CESS B blastoid tumor cells were treated in vivo with recombinant adenovirus vector expressing IL-6 cDNA, both the induction of CD8+ human CTLs against CESS cells in the spleen cells and peritoneal exudate cells and a prolongation in the survival of these mice were observed. Furthermore, SCID-PBL/hu mice were given peripheral blood lymphocytes from patients with cancer (gastric or rectal cancers) and autologous human tumor cells. The in vivo administration of recombinant adenovirus vector expressing IL-6 cDNA induced CD8+ human CTLs specific for autologous human tumor cells from human precursor T cells. The in vivo injection of the IL-6 gene also inhibited growth and metastasis in autologous human cancers. Based on the above findings, the experimental model using SCID-PBL/hu mice and the IL-6 gene delivered in vivo by an adenovirus vector might therefore provide a new strategy capable of analyzing an anti-human tumor effect and the in vivo induction of human CTLs by cytokine gene therapy without using the human body.

Adenoviridae↗

The immediate early gene of human cytomegalovirus stimulates vascular smooth muscle cell proliferation in vitro and in vivo.

Cytomegalovirus (CMV) infection has been carefully studied regarding the relationship with the vascular smooth muscle cell (VSMC) proliferation in either atherosclerosis or post-angioplasty restenosis, but its role in the vessel wall has yet to be elucidated. To clarify the pathogenic ability of CMV in the vessel wall, we transduced the immediate early (IE) gene of CMV into the VSMCs and endothelial cells (ECs) by hemagglutinating virus of Japan-liposome method. The in vitro IE gene transfer demonstrated that the conditioned medium of IE gene transferred ECs enhanced [3H]-thymidine uptake of VSMCs. The enhanced proliferation of the IE gene transferred VSMCs was observed after the stimulation by basic fibroblast growth factor. The in vivo IE gene transfer showed neointimal thickening while the control arteries did not. These findings thus suggest that the expression of CMV-IE gene in the vessel wall may play a role in the fibrocellular neointimal formation or progression of atherosclerosis in vivo.

Animals↗

Coexpression of Grb7 with epidermal growth factor receptor or Her2/erbB2 in human advanced esophageal carcinoma.

Growth factor receptors transmit intracellular signals that may be important in carcinogenesis. The Grb7 protein was recently identified as a substrate of the epidermal growth factor receptor and related Her2/ erbB2 receptor-linked tyrosine kinase activity. The Grb7 gene has been found to be coamplified with Her2/erbB2 in breast carcinomas. In this study, Grb7 expression was studied in 32 human esophageal cancers. A human Grb7 cDNA encoding for N-terminal amino acids was isolated and found to be 90% homologous to the murine counterpart. Although there was no amplification of the Grb7 gene in esophageal cancers, Grb7 mRNA was found to be overexpressed in 14 cancers (43.8%) but not in adjacent normal esophageal mucosa. It is noteworthy that coexpression of Grb7 with epidermal growth factor receptor or Her2/erbB2 was detected in 10 esophageal carcinomas (31.3%) and was significantly related to extramucosal tumor invasion (P = 0.02), whereas such a relationship was not shown by each sole expression. These findings suggest a possible relationship of Grb7 signaling in association with expression of tyrosine kinase receptors in aggressive human esophageal cancer.

Amino Acid Sequence↗

Indications for palliative reduction surgery in advanced hepatocellular carcinoma. The use of a remnant tumor index.

OBJECTIVES: To clarify the indications for and the significance of palliative reduction surgery in the multidisciplinary treatment of advanced hepatocellular carcinoma (HCC) and to propose the use of a remnant tumor index (RTI) as a simplified criterion for palliative reduction surgery in cases of advanced HCC. DESIGN: A comparison of survival based on the RTI. SETTING: A large university hospital in Japan. PATIENTS: Twenty-five patients with advanced HCC who underwent palliative reduction surgery were divided into 3 groups as follows: group 1 (n = 9), the remnant tumor after operation existed only in the liver and the RTI was less than 5.0; group 2 (n = 11), the remnant tumor after operation existed only in the liver and the RTI was greater than 5.0; and group 3 (n = 5), extrahepatic metastatic tumor existed after operation. MAIN OUTCOME MEASURES: Pathological findings and survival rate after surgery. RESULTS: There was no significant difference in the degree of macroscopic intrahepatic metastases among the 3 groups; however, both the portal vein invasion and the histological grade tended to be more severe in groups 2 and 3. The respective 1-year and 3-year survival rates for group 1 were 67% and 33%, and those for group 2 were 21% and 0%. There were no survivors in group 3 at 1 year after surgery. Significant differences were found in the survival rates between groups 1 and 2 (P < .05), and between groups 1 and 3 (P < .05). CONCLUSION: Palliative reduction surgery for advanced HCC is only considered effective for patients with both an RTI of less than 5.0 and no extrahepatic metastasis.

Aged↗

Serum carcinoembryonic antigen concentration doubling time correlates with tumor biology and life expectancy in patients with recurrent gastrointestinal carcinoma.

OBJECTIVE: To determine if carcinoembryonic antigen (CEA) concentration doubling time (DT) can predict the course of disease and characterize tumor biology. DESIGN: Retrospective case series of patients who exhibited a distinct increase in circulating CEA during disease recurrence in the routine postoperative follow-up. SETTING: A tertiary general hospital. PATIENTS: Twenty patients with recurrent gastric carcinoma and 17 patients with recurrent colorectal carcinoma. INTERVENTION: The CEA DT was determined from semilogarithmic plots of CEA concentration time courses. MAIN OUTCOME MEASUREMENTS: The quantitative analyses of the CEA DT as related to various host and tumor characteristics, modes of recurrence, and life expectancy. RESULTS: The mean CEA DTs for gastric and colorectal carcinomas were 229 days and 86 days, respectively. Although there were no significant differences with regard to patient age, tumor size, gross appearance, and histological differentiation, women had shorter CEA DT than did men. Flow cytometric analysis showed that tumors with a higher proportion of cells in S phase (> or = 15%) had significantly shorter CEA DT than those with a lower S-phase fraction (< 15%). There was a significant correlation between the CEA DT and the length of survival after the initial CEA concentration increase in patients with recurrent gastric and colorectal carcinomas. In the multiple regression analysis of patients who had been treated with curative surgery and chemotherapy, CEA DT proved to be a major independent prognostic factor. CONCLUSIONS: Carcinoembryonic antigen DT predicts life expectancy in patients with adenocarcinoma of the gastrointestinal tract. Differences in survival time are closely associated with variations in the biological aggressiveness of individual tumors.

Adult↗

Significance of alpha-fetoprotein levels for detection of early recurrence of hepatocellular carcinoma after hepatic resection.

BACKGROUND: The recurrence of hepatocellular carcinoma (HCC) after surgery is common. The present study was conducted in order to clarify the significance of alpha-fetoprotein (AFP) in the detection of the early recurrence of HCC after surgery. METHODS: Fifty-eight patients who underwent a curative hepatic resection for HCC and whose preoperative AFP levels were >100 ng/ml, were selected for this study. RESULTS: In 26 cases, the postoperative AFP levels within 3 months after surgery did not decrease to <20 ng/ml (high AFP group). In the other 32 cases, the postoperative AFP levels within 3 months after surgery decreased to <20 ng/ml (low AFP group). No significant difference was observed in clinical or pathological backgrounds. The postoperative disease free rate in the low and high AFP groups was 84.2% and 18.4%, at 1 year, 61.2 and 4.6% at 3 years, respectively. The difference was statistically significant (P < 0.01). At the time of recurrence, the AFP levels increased in 25 (96.2%) of the patients who had early recurrence within 1 year after surgery as well as in 11 of 14 (78.5%) who had recurrence >1 year after surgery. The interval from surgery to recurrence significantly correlated with the doubling time of AFP at the time of recurrence in patients with early recurrence (within 1 year after hepatectomy) (r = 0.60, P < 0.01). In cases in which the preoperative AFP level was >100 ng/ml and the postoperative AFP level did not decrease to <20 ng/ml, early recurrence within 1 year after surgery would thus be strongly suspected. CONCLUSION: The measurement of the AFP levels after surgery is therefore considered to be important in the follow-up of hepatectomized patients, especially regarding the detection of early recurrence.

Aged↗

Synchronous multiple colorectal adenocarcinomas.

BACKGROUND: The object of the present work was to characterize clinical features and the quality of preoperative examinations in patients with synchronous colorectal carcinomas, and to compare the incidence of associated benign polyps with our findings in patients with a single malignant lesion. METHODS: A retrospective evaluation of 225 patients with primary colorectal carcinoma revealed 9 cases (4.0%) of synchronous colorectal carcinomas. RESULTS: The synchronous colorectal carcinomas were located in the same anatomical segment in 7 patients and were divided into different segments in 2 patients. The accuracy of preoperative diagnosis was 55.6% by endoscopy alone and 66.7% by double contrast barium enema (DCBE) alone, while the rate was 77.8% when colonoscopy and DCBE were combined. There was a higher incidence of associated benign polyps in the group with synchronous colorectal carcinomas (55.6%) versus 28.7% for a single carcinoma (P < 0.05). The main reason why multiple lesions could not be identified preoperatively was that the distal lesions prevented examination of the proximal lesions. CONCLUSIONS: At the time of surgical resection, it is important to ascertain preoperatively whether or not a second lesion exists. If synchronous polyps are present in patients with synchronous colorectal carcinomas, they should be ablated to reduce the risk of metachronous colorectal carcinoma.

Adenocarcinoma↗

Tumor invasion and angiogenesis in early esophageal squamous cell carcinoma.

BACKGROUND AND OBJECTIVES: Although the relationship between angiogenesis and tumor proliferation or malignant potential has been previously demonstrated in several studies, early stage of cancer invasion and angiogenesis has seldom been investigated. METHODS: From the esophageal specimens of eight recently resected cases with esophageal squamous cell carcinoma, 25 areas of carcinoma-in-situ or microinvasive carcinoma were selected, and then a serial histologic investigation and immunohistochemical staining for the detection of Factor VIII-related antigen to investigate microvessels in the lamina propria mucosae beneath the lesions as a measure of angiogeneses and staining for laminin to visualize basement membrane was performed. Lymphocyte infiltration below the lesions were also estimated. In view of early cancerous invasion, histologic patterns of the growth of the lesions were divided into "flat," "expansive," and "downgrowth" patterns. RESULTS: Although downgrowth patterns are thought to be more invasive, relationships between the histologic patterns, and basement membrane staining patterns, and lymphocyte infiltration patterns were not demonstrated. However, the angiogenetic ratio (the number of vessels/cm under the lesions divided by that under normal epithelium) was observed to be significantly and closely related to tumor invasion patterns (P < 0.01), although it was not related to the destruction of the basement membrane or lymphocyte infiltration below the lesions. CONCLUSIONS: The angiogenesis of esophageal squamous cell carcinoma is closely correlated to the tumor invasion patterns in early esophageal cancerous lesions.

Carcinoma in Situ↗

Esophagojejunostomy with manual single layer suturing after a total gastrectomy for gastric cancer.

BACKGROUND: We wished to verify the clinical usefulness of manually performed single layer suturing for an esophagojejunostomy after a total gastrectomy versus stapled suturing. METHODS: We compared retrospectively 24 patients who underwent manual single layer suturing with 38 patients who underwent stapled suturing. RESULTS: Anastomotic leakage was seen in one patient (4%) with single layer suturing and one patient (3%) with stapled suturing. No anastomotic stenosis was seen in the patients with single layer suturing. There was no difference in the operative time, blood loss, postoperative days for oral intake, or the length of hospital stay between the patients with single layer suturing and those with stapled suturing. CONCLUSIONS: Manual single layer suturing is considered to be as safe as stapled suturing and is also thought to be clinically useful in reducing anastomotic failure for esophagojejunostomy.

Adult↗

Biological effects of human insulin receptor substrate-1 overexpression in hepatocytes.

The human insulin receptor substrate-1 (hIRS-1) is a key intracellular protein involved in various cytokine signaling pathways associated with cell growth. We have previously demonstrated that stable transfection and overexpression of hIRS-1 in human hepatoblastoma cells in vitro leads to the constitutive activation of the mitogen-activated protein kinase (MAPK) cascade. In this setting, hIRS-1 acts as a dominant oncogene and will induce neoplastic transformation of NIH 3T3 cells. In the present study, the biologic effects of hIRS-1 overexpression in the liver was analyzed using both clinical tumor samples and a newly developed transgenic mouse model. We have found that approximately 40% of 22 human hepatocellular carcinoma (HCC) tumors had enhanced (>200%) hIRS-1 gene expression compared with adjacent non-involved liver tissue. There was a significant relationship between the level of hIRS-1 overexpression and the tumor size; this finding suggests a possible role for hIRS-1 in tumor progression. To determine if downstream signal transduction cascades were activated by overexpression of hIRS-1 in hepatocytes, we established a transgenic mouse model using an hIRS-1 construct driven by an albumin promoter/enhancer element to direct liver specific expression. The overexpressed hIRS-1 protein was found to be tyrosyl phosphorylated and interacted with downstream SH2-containing molecules such as the p85 subunit of phosphatidylinositol-3 kinase (PI3K), Grb2 adaptor, and SHP2 phosphatase proteins. The functional consequences of hIRS-1 overexpression were reflected by constitutive activation of both the MAPK and PI3K signal transduction cascades. More important, overexpression of hIRS-1 in the transgenic liver led to increased hepatocyte DNA synthesis. Our findings indicate that hIRS-1 overexpression induces downstream signaling molecules associated with hepatocyte growth and may potentially enhance tumor progression of HCC.

3T3 Cells↗

Preserved endothelial function and morphology in canine arterial grafts under conditions of poor distal runoff.

Late graft failure is still a significant problem particularly in vessels with poor runoff. In the present study, we examined whether poor runoff conditions contributed to either functional or morphological changes in experimental canine autogenous arterial grafts. Four weeks after grafting, isometric tension studies were performed on rings obtained from femoral arterial grafts with poor runoff and the findings were compared to rings from grafts with normal runoff. The flow rate and tau variation (wall shear stress variation) in the limbs with poor runoff (18.5 +/- 4.2 ml/min, 52.9 +/- 7.0 dyne/cm2) were significantly lower than those of the control limb (66.4 +/- 9.2 ml/min, 201.1 +/- 9.6 dyne/cm2). Acetylcholine (ACh), adenosine 5'-diphosphate (ADP), and A23187 (calcium ionophore) caused comparable endothelium-dependent relaxations in the two groups. Smooth muscle relaxation in response to sodium nitroprusside was also comparable in the two groups. No apparent intimal thickening of the arterial grafts was observed in the canine arterial grafts with normal or poor runoff. Scanning electron microscopy demonstrated mild endothelial cell damage in implanted autogenous arterial grafts. At 7 to 14 days after grafting, the endothelial cell layer in both groups of grafts appeared to be normal. These results are markedly different from our previous findings with vein grafts in which pronounced intimal thickening was associated with an impairment of the endothelium-dependent responses under conditions of poor runoff. Based on these findings, the intact endothelial function and the absence of intimal thickening under conditions of poor runoff may thus explain the improved patency of autogenous arterial grafts compared to the vein grafts in aortocoronary revascularization.

Animals↗

Improved surgical results after combining preoperative hyperthermia with chemotherapy and radiotherapy for patients with carcinoma of the rectum.

PURPOSE: The aim of this study is to evaluate long-term results of preoperative hyperthermia combined with chemotherapy and irradiation (HCR therapy) in patients with carcinoma of the rectum. METHODS: Postoperative prognoses were compared among 36 patients with carcinoma of the rectum, who were given preoperative HCR therapy followed by surgery, and 52 patients undergoing surgery alone without any preoperative therapy. RESULTS: There were significant differences in the prognosis between patients given preoperative HCR therapy plus surgery and those having surgery alone, and five-year survival rates were 91.3 and 64 percent, respectively. Particularly, for patients with tumors invading beyond the muscularis propria and/or with positive lymph node metastasis, a significantly longer survival was obtained with HCR plus surgery than in surgery alone (86.5 vs. 50.9 percent and 92.9 vs. 51.7 percent, respectively). However, no significant differences were observed in the postoperative prognosis for cases with no lymph node metastasis and/or with tumors limited to the muscularis propria between these two groups. CONCLUSIONS: These data clearly demonstrated the effectiveness of preoperative HCR therapy for improving long-term results of patients with carcinoma of the rectum, especially those demonstrating an advanced stage of disease.

Aged↗

Tumor size as a simple prognostic indicator for gastric carcinoma.

BACKGROUND: Tumor size can be measured easily before or during operation with no special tools, but its prognostic use in patients with gastric carcinoma is still unclear. METHODS: Clinicopathologic data of 479 patients who underwent curative operation for gastric carcinoma were studies. The relationship between tumor size and survival of patients was investigated. RESULTS: The patients were divided into three groups: 182 with tumors measuring < 4 cm (group I), 252 with tumors of 4-10 cm (group II), and 45 with tumors of > or = 10 cm (group III). The 10-year survival rates for group I, II, and III patients were 92%, 66% and 33%, respectively (p < 0.01), and the three groups were significantly different with regard to depth of invasion (p < 0.01), number and level of lymph node metastasis (p < 0.01), and stage of disease (p < 0.01). Multivariate analysis indicated that tumor size independently influenced the survival of patients. CONCLUSIONS: Tumor size clinically serves as a simple predictor of tumor progression and survival of patients in gastric carcinoma.

Adenocarcinoma↗

A comparison of open and laparoscopic cholecystectomy for patients with cirrhosis.

To evaluate the benefits of performing laparoscopic cholecystectomy (LC) in patients with cirrhosis, data on 13 patients with liver cirrhosis who underwent cholecystectomy for gallstones between 1989 and 1995 were retrospectively collected from charts filed at Fukuoka City Hospital. These 13 patients were classified into two groups; one, comprised of 7 who underwent LC, and another, comprised of 6 who underwent open cholecystectomy (OC). No statistical differences were observed in the duration of surgery or the intraoperative blood loss between the two groups; however, the C-reactive protein (CRP) level in the serum was significantly higher in the OC group than in the LC group. LC was followed by a significantly earlier resumption of a normal diet (P < 0.05) and a shorter hospital stay (P < 0.05) in comparison to OC. All of the patients who underwent OC had an uneventful clinical course; however, one of the patients who underwent LC suffered from intractable ascites postoperatively. The difference in the cost of hospitalization between the two groups was not statistically significant. These findings suggest that the therapeutic significance of performing LC in patients with cirrhosis should be assessed after carefully evaluating all factors including mortality, morbidity, and cost-effectiveness. Thus, further controlled trials are necessary.

Aged↗

The appearance of a normal appendix on barium enema examination does not rule out a diagnosis of chronic appendicitis: report of a case and review of the literature.

We report herein the rare case of a 15-year-old girl with chronic appendicitis in whom the appendix was clearly depicted by a barium enema (BE) examination. The patient presented with a 4-month history of diffuse abdominal pain and tenderness in the lower abdomen. Neither computed tomography nor ultrasonography showed any abnormal findings in the lower abdomen or pelvic cavity. Furthermore, BE examination depicted an appendix filled with the contrast medium. However, at elective surgery, she was found to have chronic appendicitis which was later confirmed histologically. Following this case report, a discussion on the value and limitations of BE examination for the diagnosis of acute and chronic appendicitis is presented.

Abdominal Pain↗