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Biomedical subjects

K Sugimachi

Publications and source records attributed to K Sugimachi.

At least 253 records · Page 14Linked to original sources

Expression of matrix metalloproteinase-9 in surgically resected intrahepatic cholangiocarcinoma.

BACKGROUND: Matrix metalloproteinase-9 (MMP-9) has recently been reported to be related to cancer cell invasion. This study was performed to clarify the expression of MMP-9 in surgically resected intrahepatic cholangiocarcinoma (IHCC). METHODS: In 37 patients with IHCC who underwent a surgical resection, the expression of MMP-9 and the clinicopathologic characteristics of MMP-9-positive IHCC were investigated. The expression of MMP-9 was immunohistochemically detected in 16 (43%) of 37 IHCC. The patients were divided into MMP-9 (-) IHCC (n = 21), MMP-9 (+) IHCC (n = 12), and MMP-9 (++) IHCC (n = 4). RESULTS: The survival rate after surgical resection in patients with MMP-9 (-), (+), and (++) IHCC, was 66%, 39%, and 0% at one year, 50%, 32% and 0% at 3 years, respectively (P = .001). The incidence rate of lymph node metastasis was 6 (28%) of 21 in MMP-9 (-) patients, 7 (58%) of 12 in MMP-9 (+) patients and 4 (100%) of 4 in MMP-9 (++) patients. The incidence rate of lymph node metastasis increased in proportion to an increase in the expression of MMP-9 in IHCC (P = .02). Recurrence in the lymph node was more common in patients with MMP-9 (+) and (++) cancers than in those with MMP-9 (-) cancers. CONCLUSIONS: The expression of MMP-9 in IHCC was a prognostic factor related to lymph node metastasis.

Adult↗

[Study on CAF + medroxyprogesterone acetate (MPA) therapy for advanced or recurrent breast cancer--comparison between MPA 600 mg and 1,200 mg. Kyushu CAFT Therapy Study Group (Third Study)].

To find the optimal dose of MPA for combined use with CAF therapy for advanced or recurrent breast cancer, a randomized comparative study with a MPA 1,200 mg group and 600 mg group was carried out multi-institutionally. The response rate of complete cases was 37.5% (12/32) in the 1,200 mg group and 36.6% (15/41) in the 600 mg group, showing no difference between the two groups. There were no differences in either the duration of response or the survival term. The major adverse effects and abnormal laboratory test values included alopecia, nausea and vomiting, general fatigue, anorexia and leukopenia, with no difference in incidence between the groups. Moon face, genital hemorrhage and body weight increase, which are thought to be caused by MPA, were found in both groups without a significant difference in incidence. The results of this study revealed no differences in effectiveness or safety between MPA 1,200 mg and 600 mg, suggesting that MPA for combined use with CAF is fully effective at a dose of 600 mg.

Adult↗

Extended resection of the pulmonary artery and the aorta for primary lung cancer. Report of a case.

We report a case of squamous cell carcinoma of the lung in which a left pneumonectomy combined resection of the pulmonary artery and aorta was performed using a cardiopulmonary bypass. The bifurcation of the pulmonary artery was repaired with a pericardial patch and the descending aorta was replaced with an artificial vessel Eleven months later, the patient underwent dissection of the contralateral mediastinal lymph nodes because of a recurrence of the disease. Even though pulmonary metastases have again recently appeared, he is alive and doing well two years after operation. To obtain a better prognosis in cases demonstrating an involvement of the bifurcation of pulmonary artery, more effective combined treatment still needs to be developed.

Adult↗

[Positron emission tomography for detection of lymph node metastases in lung cancer].

Although radiography, computed tomography (CT), and magnetic resonance imaging are still the methods of choice for the study of lung cancer, they have certain limitations in the evaluation of mediastinal lymph node metastases. Positron emission tomography (PET) with 18F-fluoro-2-deoxy-D-glucose (FDG) has recently emerged as a practical and useful imaging modality in patients with lung cancer. We evaluated the usefulness of FDG-PET in the detection of mediastinal lymph node metastases and then compared the findings with the results of CT by region based on the histological diagnosis. For FDG-PET, the sensitivity, specificity and accuracy were 93%, 76%, and 98%, respectively, whereas, for CT, this was 65%, 87%, and 82%, which showed significant differences. FDG-PET is significantly more accurate than CT in lymph node staging of lung cancer, and also can improve the diagnostic accuracy in distant metastases.

Fluorodeoxyglucose F18↗

MST-16, a novel bis-dioxopiperazine anticancer agent, ameliorates doxorubicin-induced acute toxicity while maintaining antitumor efficacy.

MST-16 [4,4-1,2-(ethanediyl)bis(1-isobutoxycarbonyl-oxy-methyl-2,6-pipera zinedione)], recently approved as an oral anticancer drug for clinical use in Japan, was evaluated as a chemotherapeutic agent in combination with doxorubicin (DOX) in vitro and in vivo. Cytotoxicity was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and murine Colon 26 and human KATO III adenocarcinoma cells were used. The combination index derived from these cytotoxic values indicated a synergistic interaction between DOX and MST-16 or its active metabolite, ICRF-154 (1,1'-ethylenedi-3,5-dioxopiperazine). A maximal tolerated dose of DOX administered to female BALB/c mice bearing a solid Colon 26 tumor resulted in severe body weight loss and diarrhea, but a limited tumor growth delay (1.8 days). However, when combined with an oral dose of MST-16, DOX-induced body weight loss and diarrhea were significantly ameliorated, and an additive tumor growth delay (8.7 days) was obtained. The LD50 of DOX administered i.p. to control female BALB/c mice increased more than 1.5-fold when combined with MST-16. Thus, MST-16 ameliorates DOX-induced acute toxicity while maintaining antitumor efficacy. These results indicate that MST-16 may be effective chemotherapy for cancer patients when combined with DOX.

Animals↗

Cytokine patterns and the effects of a preoperative steroid treatment in the patients with abdominal aortic aneurysms.

BACKGROUND: The aim of this study was to investigate the cytokine patterns of patients with abdominal aortic aneurysms and the effects of preoperative steroid administration on surgical stress. METHODS: From January 1996 to August 1996, 20 consecutive patients underwent an elective reconstruction of infrarenal abdominal aortic aneurysms. The patients were randomly divided into two groups consisting of a control group (n=10) and a steroid group (n=10), in whom 1 g of methylprednisolone was intravenously administered two hours before the operation. MEASURES: Interleukin-6 was serially measured and the perioperative parameters including C-reactive protein were compared between both the control and the steroid groups. RESULTS: The interleukin-6 values in the steroid group immediately after declamping, as well as at one and three postoperative days were significantly lower than those in the control group. C-reactive protein values at one postoperative day in the steroid group were also significantly lower than those in the control group. In one patient with a ruptured abdominal aortic aneurysm, the interleukin-6 values were higher than those in the patients undergoing elective surgery throughout the study. CONCLUSIONS: These results thus suggest that preoperative steroid administration using methylprednisolone in patients with abdominal aortic aneurysms appears to reduce surgical stress by decreasing cytokine release.

Aged↗

The effect of carbon dioxide pneumoperitoneum on the portal hemodynamics in a portal-hypertensive rat model.

As use of laparoscopic surgery grows, various complications with pneumoperitoneum have been reported. However, there are no reports on the relation between the carbon dioxide (Co2) pneumoperitoneum and portal hemodynamics. The purpose of this study was to determine how the pneumoperitoneum affects the portal hypertensive state. Portal-hypertensive rats, control rats, and sham operation rats were studied. The mean arterial pressure, portal venous pressure, central venous pressure, red blood flow volume of the viscera, and liver and renal function were investigated. The findings of this study suggest that Co2 pneumoperitoneum at less than 10 mm Hg does not present any undue risk to the portal hemodynamics in portal-hypertensive rats; however, more attention should be paid to the IAP in PHT patients undergoing surgery.

Animals↗

Clinicopathologic features of patients with hepatocellular carcinoma surviving >10 years after hepatic resection.

BACKGROUND: This study was performed to clarify the clinicopathologic features of hepatocellular carcinoma (HCC) patients surviving >10 years after hepatic resection. METHODS: Between January 1971 and April 1987, 142 patients underwent hepatic resection. Thirty-nine patients who died of surgical morbidity (surgical mortality rate: 27.5%) were excluded from this study. Among the 103 patients who survived and were observed for >10 years after surgery, 12 patients (11.7%) survived >10 years after hepatectomy. The surviving patients were divided into 2 groups: 10-year survivors (n = 12) and nonsurvivors (n = 91). A comparative study between the two groups was made. RESULTS: Preoperative liver function tests such as the indocyanine green retention test at 15 minutes and albumin levels showed that 10-year survivors had better liver function than nonsurvivors. With regard to virus markers, 5 of 12 patients (41.7%) were positive for hepatitis B surface antigen (HBs-Ag) and the incidence of hepatitis B virus-related HCC was significantly higher than in nonsurvivors (P = 0.020). The results also showed that 4 of 12 long term survivors had hepatitis C virus (HCV) antibody and 1 patient did not have any HCV antibody or HBs-Ag. In two other patients, the HCV antibody was not measured and HBs-Ag was negative. Among four patients with the HCV antibody, the serum HCV RNA concentration, measured by branched DNA probe assay, was <0.5 in 3 patients and 1.72 in 1 patient. Therefore, the HCV RNA concentration tended to be lower in 10-year survivors. Tumor recurrence occurred in 8 of the 10-year survivors. Solitary recurrence was observed in five patients whereas multiple recurrence was observed in three patients. All five patients with solitary recurrence underwent a second resection. CONCLUSIONS: Based on the results of the current study, good liver function, HBs-Ag positivity, and a low concentration of serum HCV RNA in HCV-related HCC should be considered potentially good predictors of a long term survival.

Adult↗

Proliferative activity of cancer cells in front and center areas of carcinoma in situ and invasive sites of esophageal squamous-cell carcinoma.

Intraepithelial carcinoma contiguous with invasive squamous-cell carcinoma is a conspicuous feature of esophageal cancer. However, whether the mechanism of intraepithelial spreading is due to cell proliferation or field carcinogenesis has yet to be clarified. This study investigated the mechanism of intraepithelial spreading by measuring the cell proliferative activity using argyrophilic nucleolar organizer region (AgNOR) and proliferating cell nuclear antigen (PCNA)-positive cell counting. We examined the AgNOR number and PCNA-positive ratio (PCNA ratio) in the center and outer edge of intraepithelial carcinoma and in the center and deep margin of invasive squamous-cell carcinoma of the esophagus in 50 specimens from 18 cases of esophageal squamous-cell carcinoma concomitant with contiguous intraepithelial carcinoma. The proliferative activity was thus found to differ between the normal epithelium and cancerous lesions (p < 0.001), between intraepithelial carcinoma and invasive cancer (p < 0.001) and between deep margin and center areas of invasive cancer (p < 0.005). On the other hand, such activity was observed to be similar in the center and outer edge of the intraepithelial spread. These findings suggest that cell proliferation is the main mechanism of tumor progression at the invasive site of cancer, whereas in intraepithelial carcinomatous areas, "field carcinogenesis" or a paracrine mechanism, and not cell proliferation, is thought to be the cause of intraepithelial spread of esophageal cancer. These results therefore support the concept of field carcinogenesis.

Carcinoma in Situ↗

Multifocal occurrence of gastric carcinoma in patients with a family history of gastric carcinoma.

BACKGROUND: Smoking and alcoholic beverage drinking habits as well as a family history of cancer are well known risk factors for the multifocal occurrence of squamous cell carcinoma of the esophagus and the head and neck region. However, the role of these risk factors in multiple gastric carcinoma remains to be clarified. The purpose of this study was to examine the risk factors for multiple gastric carcinoma. METHODS: The smoking and drinking habits as well as the family history of 157 patients with synchronous multiple gastric carcinoma and 157 patients with solitary gastric carcinoma who were similar with regard to gender, age, stage of the tumor, and year of admission were investigated. The risk of a multiple occurrence of gastric carcinoma also was elevated using the odds ratio (OR). RESULTS: The ORs of a multifocal occurrence of gastric carcinoma in patients who currently smoked and drank alcoholic beverages were 1.1 and 0.8, respectively, although the ORs were not related to the quantity of smoking or drinking. In patients with a close relative with gastric carcinoma the OR was 2.1 (95% confidence interval [CI], 1.3-3.7). In those patients with > or =2 close relatives with gastric carcinoma, the OR increased to 5.1 (95% CI, 1.2-21.1). Conversely, no significant elevation in the ORs was recognized regarding a family history of other cancers. CONCLUSIONS: In this study, a family history of gastric carcinoma was found to be clearly associated with the multifocal occurrence of gastric carcinoma; however, no significant correlation between the multifocal occurrence of gastric carcinoma in these patients and their smoking and drinking habits was recognized.

Alcohol Drinking↗

A novel frizzled gene identified in human esophageal carcinoma mediates APC/beta-catenin signals.

A novel member of the human frizzled (Fz) gene family was cloned and found to be specifically expressed in 3 of 13 well differentiated (23%), 13 of 20 moderately differentiated (62%), and 12 of 14 poorly differentiated (86%) squamous cell esophageal carcinomas compared with the adjacent uninvolved normal mucosa. The FzE3 cDNA encodes a protein of 574 amino acids and shares high sequence homology with the human FzD2 gene particularly in the putative ligand binding region of the cysteine-rich extracellular domain. Functional analysis revealed that transfection and expression of the FzE3 cDNA in esophageal carcinoma cells stimulates complex formation between adenomatous polyposis coli (APC) and beta-catenin followed by nuclear translocation of beta-catenin. Furthermore, cotransfection of a mutant construct encoding a FzE3 protein with a C-terminal truncation completely inhibited the interaction of APC with beta-catenin in cells. Finally, coexpression of FzE3 with Lef-1 transcription factor enhanced beta-catenin translocation to the nucleus. These observations suggest that FzE3 gene expression may down-regulate APC function and enhance beta-catenin mediated signals in poorly differentiated human esophageal carcinomas.

Adenomatous Polyposis Coli Protein↗

A novel variant of human Grb7 is associated with invasive esophageal carcinoma.

The cDNAs of a putative growth factor-bound (Grb) 7 signal transduction molecule and Grb7V novel splice variant were isolated from an invasive human esophageal carcinoma. Although both Grb7 isoforms share homology with the Mig-10 cell migration gene, the Grb7V isoform lacks 88 base pairs in the C terminus; the resultant frame shift leads to substitution of an SH2 domain with a short hydrophobic sequence. The wild-type Grb7 protein, but not the Grb7V isoform, is rapidly tyrosyl phosphorylated in response to EGF stimulation in esophageal carcinoma cells. Analysis of human esophageal tumor tissues and regional lymph nodes with metastases revealed that Grb7V was expressed in 40% of Grb7-positive esophageal carcinomas. More importantly, Grb7V expression was enhanced after metastatic spread to lymph nodes as compared to the original tumor tissues. Finally, transfection of an antisense Grb7 RNA expression construct lowered endogenous Grb7 protein levels and suppressed the invasive phenotype exhibited by esophageal carcinoma cells. These findings suggest that Grb7 isoforms are involved in cell invasion and metastatic progression of human esophageal carcinomas.

Adaptor Proteins, Signal Transducing↗

Natural killer cell activity in patients with hepatocellular carcinoma: a new prognostic indicator after hepatectomy.

BACKGROUND: Natural cytotoxicity mediated by natural killer (NK) cells is believed to play an important role in host anticancer defense mechanisms. The aim of this study was to examine the prognostic significance of NK cell activity after hepatectomy in patients with hepatocellular carcinoma. METHODS: The NK cell activity in 210 patients with hepatocellular carcinoma was measured and evaluated in relation to clinicopathologic variables using univariate and multivariate analyses. RESULTS: The NK cell activity was decreased significantly in hepatocellular carcinoma patients compared with the control groups (P < 0.001). No correlation was observed between NK cell activity and the clinicopathologic variables. Multivariate analyses indicated that NK cell activity as well as intrahepatic metastases, platelet count, and serum albumin level were independent prognostic factors. CONCLUSIONS: This study suggests that the preoperative NK cell activity will help predict recurrence and prognosis after hepatectomy in patients with hepatocellular carcinoma.

Adult↗

Long-term survival of patients with stage IV gastric carcinoma.

BACKGROUND: Survival of patients with Stage IV (based on general rules established by the Japanese Research Society for Gastric Cancer) gastric carcinoma often is unfavorable. Among patients with a poor prognosis, a few do survive > 5 years. The authors examined pathologic and biologic features of tumors of long term survivors. METHODS: The authors analyzed data from 442 patients with Stage IV gastric carcinoma, including 20 surviving for > 5 years after gastrectomy (Group A) and 422 who died of gastric carcinoma within 5 years (Group B). Mutant p53 was immunohistochemically stained using the monoclonal antibody PAb1801. Proliferative activity was estimated by argyrophilic nuclear organizer region (AgNOR) staining and proliferating cell nuclear antigen (PCNA) staining. RESULTS: Group A had smaller and more localized tumors than Group B (P < 0.05 and P < 0.01, respectively). Lymphatic or venous invasion and peritoneal dissemination were less frequent in Group A than in Group B (P < 0.01). Abnormalities of p53 expression were found in 3 of the 14 tumors in Group A (21%), a value significantly lower than the 58 of 118 tumors in Group B (49%; P < 0.05). AgNOR count and percentage of PCNA labeling were not significantly different between Groups A and B. A multivariate analysis showed that lymph node dissection, liver metastasis, gastric resection, venous invasion, and tumor size were independent prognostic factors. CONCLUSIONS: Even in patients with Stage IV gastric carcinoma, radical gastrectomy and extensive lymph node dissection can lead to long term survival. The authors believe that combination analysis of pathologic features and p53 overexpression predict length of survival for patients with Stage IV gastric carcinoma.

Adult↗

Family aggregation of carcinoma of the hypopharynx and cervical esophagus: special reference to multiplicity of cancer in upper aerodigestive tract.

The role of family history in the multiple occurrence of cancer in the upper aerodigestive tract (UADT) remains unclear. The family histories of close relatives were examined in 167 patients with either hypopharyngeal or cervical esophageal cancer (PhCe cancer) and in 167 control subjects with benign diseases. The odds ratio for PhCe cancer was 2.6 in relation to family history of UADT cancers. Based on the family histories of close relatives, 167 cases with PhCe cancer were divided into 3 groups (Group I, 18 cases with a family history of UADT cancer; Group II, 37 cases with a family history of other cancers; Group III, 112 cases with no family history of any cancers). The mean age of the cases in group I was 59.4, which was younger than in group III (64.2). Second primary squamous-cell carcinomas in the UADT were more frequently recognized in group I (39%) than in group III (11%). However, no differences were observed in the smoking and drinking habits of male patients between each group. These results thus suggest that a family history of UADT cancers appears to be associated with the multiple occurrence of UADT cancers as well as the development of PhCe cancer.

Aged↗

Identification of cystatin B in human esophageal carcinoma, using differential displays in which the gene expression is related to lymph-node metastasis.

Identification of the genes that are specifically expressed in either tumor or normal tissue is important for understanding cancer biology. Using differential displays, we obtained one gene which was specifically expressed in normal tissue but is only rarely expressed in carcinoma tissue of the human esophagus. The sequence of this gene was identical with cystatin B, known to be one of the cysteine-proteinase inhibitors, mainly inhibiting cathepsin L. There is little information on the clinical significance of cystatin B expression in human esophageal carcinoma. We thus studied the mRNA expression of cystatin B in 45 tumor/normal pair specimens of the esophagus, using the semi-quantitative reverse transcriptase polymerase chain reaction technique. The expression of cystatin B in tumor tissue was found to be markedly decreased compared with that of the corresponding normal tissue. The cases with a tumor/normal ratio of less than 0.5 showed high frequency of lymph-node metastasis and more advanced clinical stage as compared with those whose tumor/normal ratio was equal to or more than 0.5. The decreased expression of cystatin B protein in carcinoma tissue was confirmed by immunohistochemical staining. Our study suggests that reduced expression of cystatin B in esophageal-carcinoma tissue is associated with lymph-node metastasis and may therefore prove to be a useful marker for predicting the biologic aggressiveness of human esophageal carcinoma.

Cathepsin L↗

Interrelation between tumor-associated cell surface glycoprotein and host immune response in gastric carcinoma patients.

BACKGROUND: Expression of changes in cell surface glycoprotein may correlate with the malignant potential and development of gastric carcinoma. Immunologic defense mechanisms of the host against the tumor can be effective in preventing the development of gastric carcinoma. The authors studied the effects of immunologic defense of the host against the tumor, using infiltration of S-100 protein positive dendritic cells (DC) as a marker. In cases with or without changes in the surface glycoprotein of tumor cells, determinations were made by binding of Helix pomatia agglutinin (HPA). METHODS: Paraffin blocks of 123 gastric carcinoma specimens were prepared for immunohistochemical staining with the antibody against HPA and S-100 protein. Clinicopathologic factors and patient prognosis were examined for each indicator. RESULTS: Patients with HPA positive tumors had a more aggressive character in several important prognostic aspects and poorer 5-year survival rates compared with patients with HPA negative tumors. The degree of infiltration of DC had no particular correlation with pathologic factors, and there was no significant difference between the prognosis of patients with slight and marked DC infiltration. In the HPA negative patients there was no significant difference in the 5-year survival rates between patients with slight and marked DC infiltration; however, in the HPA positive patients the 5-year survival rates of patients with marked infiltration of DC were higher. Further investigation showed that patients with marked DC infiltration had better 5-year survival rates than patients with slight DC infiltration, especially in patients with HPA positive and histologically advanced disease. CONCLUSIONS: Patients with a higher immunologic defense against cancer cells, as indicated by marked infiltration of DC, had a better prognosis in cases of gastric carcinomas of highly malignant potential, as indicated by a positive HPA.

Adult↗

A microsatellite instability analysis in neuroblastoma based on a high resolution fluorescent microsatellite analysis.

It has recently been reported that mismatch repair enzymes, which are one type of DNA repair enzymes, are the causative genes for a major group of hereditary non-polyposis colon cancers (HNPCC). Abnormalities in the mismatch repair system can be monitored by observing instability at the microsatellite loci (MSI) in cancer cells. MSI has been reported not only in tumors associated with hereditary non-polyposis colorectal cancer but also in sporadic forms of various tumors. No correlation between pediatric malignant tumors and the mismatch repair system has yet been reported. In the present study, we examined the frequency of MSI in 21 neuroblastomas, which are the most common solid tumors in childhood, using a high resolution fluorescent microsatellite analysis. MSI on five microsatellite loci was detected in none of the 21 samples. Other mechanisms independent of mismatch repair deficiency may thus play a role in both tumorigenesis and the development of neuroblastoma.

Child↗