Biomedical subjects

K Sugimachi

Publications and source records attributed to K Sugimachi.

At least 127 records · Page 7Linked to original sources

PubMed2000

CYFRA 21-1 determination in patients with esophageal squamous cell carcinoma: clinical utility for detection of recurrences.

BACKGROUND: While there are reports that CYFRA 21-1 is a useful tumor marker, to our knowledge the clinical utility of this marker to detect recurrences for squamous cell carcinoma of the esophagus has not been addressed. METHODS: By immunoradiometric assay, human serum levels of CYFRA 21-1, SCC antigen and CEA were measured in esophageal squamous cell carcinoma patients prior to their initial treatment. Monthly follow-ups of these tumor markers was done after surgery. RESULTS: The diagnostic sensitivity of CYFRA 21-1 was 43.9% (18 of 41), a value superior to that for SCC antigen (26.8%) and CEA (17.0%) (P < 0.05). The positive rates of CYFRA 21-1 increased with progression of the disease, 22.2% of pTNM Stage 0-IIA and 77.8% of pTNM Stage IIB/III (P = 0.013), whereas SCC antigen and CEA rates were not related to pTNM stage. Among 13 patients with clinical evidence of a recurrence, 76.9% (10 of 13) exhibited an increase in CYFRA 21-1, and this increase was evident before clinical detection of the recurrence in 9 of these 13 patients (69.2%). Consequently, postoperative elevations of serum CYFRA 21-1 levels were indicative of a tumor recurrence 1-13 months before acquisition of clinical and radiological data. CONCLUSIONS: The assay of CYFRA 21-1 is useful not only for diagnosis but also for close monitoring of patients with esophageal squamous cell carcinoma.

Antigens, Neoplasm↗

PubMed2000

p53 polymorphism in human papillomavirus-associated esophageal cancer.

Human papillomavirus type 16/18 (HPV-16/18) is implicated in the pathogenesis of squamous cell carcinoma (SCC) of the cervix and esophagus. The arginine allele at codon 72 of p53 was found to be more susceptible to degradation by HPV E6 protein than is the proline allele in vivo, thus resulting in a high frequency of cervical SCC in individuals homozygous for arginine at the codon. There are controversial results from several clinical studies of cervical SCC. In the present study, encoding regions of p53 codon 72 and HPV-16/18 E6 were directly sequenced, using pairs of primary esophageal SCC tissue and corresponding normal mucosa, which were from 75 patients (Japanese, n = 38; Chinese, n = 37). The arginine allele alone was detected in 70.6% (12 of 17) of HPV-positive cases but only in 43.1% (25 of 58) of HPV-negative cases (P < 0.05). In contrast, such a significant correlation between p53 polymorphism and HPV infection was not evident in corresponding normal mucosae. Because our findings between tumor specimens and the normal mucosae differed, we suggest that the frequent loss of proline allele in HPV-associated carcinogenesis of the esophagus major plays some role. The particular type of p53 polymorphism may indicate a potential candidate for HPV-associated SCC.

Alleles↗

PubMed2000

High expression of vascular endothelial growth factor is associated with liver metastasis and a poor prognosis for patients with ductal pancreatic adenocarcinoma.

BACKGROUND: Vascular endothelial growth factor (VEGF), a recently identified growth factor with significant angiogenic properties, is a multifunctional angiogenic cytokine that is expressed in many tumors. High VEGF expression has been shown to correlate with the incidence of metastasis and poor prognosis in various cancers. In this study, the authors investigated VEGF expression and microvessel density (MVD) in ductal pancreatic adenocarcinoma and examined the correlations among VEGF expression, clinicopathologic factors, and clinical outcome. The authors especially focused on the correlation between VEGF expression and liver metastasis. METHODS: Paraffin embedded tumor specimens of 142 surgically resected pancreas carcinoma were immunohistochemically stained for VEGF and MVD. The correlations among VEGF expression and MVD, clinicopathologic factors, and clinical outcome were then statistically analyzed. RESULTS: One hundred thirty-two (93%) of 142 ductal pancreatic adenocarcinomas were positive for VEGF protein by immunohistochemistry. A significant correlation was observed between VEGF positivity and MVD (P < 0.0001). Multivariate logistic regression analysis indicated a significant association between high VEGF expression and liver metastasis (P = 0.010) but no other factors, such as age, tumor size, histologic type, lymph node metastasis, venous invasion, neural invasion, peritoneal metastasis, or local recurrence. Patients with tumors that showed moderate or high VEGF expression had significantly shorter survival than patients with low VEGF expression or none at all in their tumors (P < 0.05). CONCLUSIONS: These results indicate that VEGF expression is closely correlated with MVD and seems to be an important predictor for both liver metastasis and poor prognosis in ductal pancreatic adenocarcinoma.

Adult↗

PubMed2000

Diminished expression of ING1 mRNA and the correlation with p53 expression in breast cancers.

p33(ING1) is a novel candidate tumor suppressor and its overexpression induces growth arrest or apoptosis in different cell lines. These functions of p33(ING1) depend largely on the activity of p53, and p53-dependent activation of the transcription from the p21/WAF1 promoter also requires p33(ING1). We examined the expression of ING1 mRNA in breast cancer cell lines and clinical breast cancer tissues, using quantitative RT-PCR and real time TaqMan technology. In breast cancer cell lines, ING1 mRNA was expressed at almost the same level. However, in a comparison between the cancer and matched normal tissues, a significant decrease in ING1 mRNA expression was found in 17 of 24 (70.8%) breast cancer tissues. We also examined the correlation between ING1 mRNA expression and p53 expression. There was a significant decrease of ING1 mRNA in nine of 15 tumors negative for p53 immunostaining, most of which were considered to have wild type p53. In these tumors, p53 may not function in case of a decreased expression of p33(ING1), and the lack of cell cycle regulation may correlate with the carcinogenesis and tumor progression.

Breast Neoplasms↗

PubMed2000

Altered expression of Fhit in carcinoma and precarcinomatous lesions of the esophagus.

The FHIT gene, located at chromosome 3p14.2, is a tumor suppressor gene often involved in tumors resulting from exposure to environmental carcinogens. We studied 46 pairs of esophageal primary tumors and corresponding normal squamous mucosa specimens by molecular genetic and immunohistochemical methods to investigate the role of the FHIT gene in esophageal carcinoma. In addition, we studied several different types of lesions, such as carcinoma in situ or dysplasia by immunohistochemistry. Loss of heterozygosity at or around the FHIT gene was observed in 35 (76%) primary tumors. Immunohistochemical detection of Fhit protein in the primary tumors demonstrated that 14 (30%) were positive and 32 (70%) were negative. We observed concordance between loss of Fhit protein and loss of heterozygosity and between loss of Fhit protein and RNA abnormalities. Because the FHIT/FRA3B locus is susceptible to damage by environmental carcinogens, we investigated the correlation between Fhit expression and smoking or alcohol habits. In this relatively small study, the patients who were both heavy users of tobacco and alcohol showed a significantly higher frequency of loss of Fhit expression than those who were light users. Noncarcinomatous squamous epithelium showed positive Fhit reactivity in most cases; however, five showed negative Fhit reactivity. Interestingly, all of these five patients had habits of heavy use of tobacco and alcohol. Eight of 12 carcinomas in situ, 2 of 4 severe dysplasias, 4 of 8 moderate dysplasias, and 3 of 9 mild dysplastic lesions showed negative Fhit reactivity. These findings indicated that loss of Fhit expression may be an early event in the development of human esophageal carcinoma and may occur even in normal-appearing squamous epithelium in some patients heavily exposed to environmental carcinogens.

Acid Anhydride Hydrolases↗

PubMed2000

The significance of thymidine phosphorylase activity in hepatocellular carcinoma and chronic diseased livers: a special reference to liver fibrosis and multicentric tumor occurrence.

The role of thymidine phosphorylase (TP), an angiogenic factor, in hepatocellular carcinoma (HCC) remains unclear. The aim of this study was to clarify the significance of TP in HCC. Thirty-seven patients with HCC, who underwent hepatectomy, were included. The TP activity in both cancerous and non-cancerous parts of livers were measured by an enzyme-linked immunosorbent assay. Another 11 patients without HCC were used to evaluate the TP activity in the non-cancerous parts of livers. Both the cancerous and non-cancerous TP activities were clinico-pathologically investigated with special reference to the multicentric occurrence of HCCs and the degree of liver fibrosis; consisting of normal, fibrosis and cirrhosis. The TP activity in the cancerous part was 94.6 +/- 70.2 U/mg protein, while that in non-cancerous parts of the liver was 80.9 +/- 48.8 U/mg protein. No significant difference was observed. The TP activity in the cancerous part did not correlate with any clinicopathological variables, such as tumor differentiation, portal vein invasion, intrahepatic metastases and prognosis. However, the TP activity in the non-cancerous parts of the liver correlated with the degree of fibrosis (normal/fibrosis/cirrhosis = 34:74:90 U/ mg protein, respectively). Furthermore, regarding the correlation between TP activity in the non-cancerous parts and the simultaneously multicentric occurrence of HCC, the TP activity in the multicentric group (n = 8; 121 U/mg protein) was significantly higher than that in the non-multicentric group (n = 29; 70 U/mg protein). The TP activity in the non-cancerous parts increased in proportion to the degree of liver fibrosis. Furthermore, it is suggested that the higher TP activity in the non-cancerous part is related to the multicentric occurrence of HCCs.

Adult↗

PubMed2000

Evaluation of p53 alterations in occult lymph node metastases.

BACKGROUND AND OBJECTIVES: This study was designed to evaluate p53 alterations in occult lymph node metastases. METHODS: We examined 41 patients with stage I non-small-cell lung cancer. We investigated p53 gene mutation by polymerase chain reaction and single-strand conformation polymorphism analysis of exons 5-8, p53 protein accumulation by immunostaining with monoclonal antibody DO-7, and detection of tumor cells in lymph nodes by immunohistochemistry with monoclonal antibodies to cytokeratin (CK). RESULTS: p53 gene mutation was detected in 34% of tumors and nuclear p53 accumulation in 46%. CK-positive cells in the hilar and mediastinal region lymph nodes were detected in 43.9% of patients and 29.3%, respectively. Of the 14 cases with p53 mutation and the 19 cases with p53 accumulation, 12 and 15 had micrometastases in the hilar or mediastinal lymph nodes, respectively. However, p53 alterations were not significantly associated with occult lymph node metastases. In cases with occult lymph node metastases, the 5-year survival was 81. 9% for the p53 wild-type group and 45.8% for the p53 mutation group. CONCLUSIONS: p53 alterations are not correlated with occult lymph node metastases, while p53 gene mutation is considered to be an unfavorable prognostic marker in patients with occult lymph node metastases. J. Surg. Oncol. 2000;73:143-147.

Aged↗

PubMed2000

Grb7 signal transduction protein mediates metastatic progression of esophageal carcinoma.

We have previously reported the association of tumor cell invasion with expression of growth factor receptor-bound protein 7 (Grb7). This molecule contains a Src homology 2 (SH2) domain and shares structural homology with a cell migration molecule designated Mig-10 found in Caenorhabditis elegans. In the present study, Grb7 expression was analyzed in human esophageal carcinomas with or without metastatic spread. The Grb7 protein was overexpressed in 14 of 31 esophageal carcinomas as compared to the adjacent normal mucosa (45%) and this finding was significantly correlated with the presence of lymph node metastases. We also identified that Grb7 protein in esophageal carcinoma cells was phosphorylated on tyrosine by epidermal growth factor as well as attachment to extracellular matrix proteins including fibronectin. Such fibronectin-dependent phosphorylation of Grb7 was regulated by integrin signaling that leads to the interaction with focal adhesion kinase protein. Furthermore, ectopic expression of a Grb7-SH2 dominant-negative fragment inhibited the fibronectin-dependent phosphorylation of endogenous Grb7, and reduced migration of esophageal carcinoma cells into fibronectin. Our results suggest a role of Grb7 mediated signal transduction in generation of an invasive cell phenotype against extracellular matrix, and thus contributes to metastatic progression of human esophageal carcinoma.

Adenocarcinoma↗

PubMed2000

Clinicopathological characteristics of mucinous carcinoma of the colon and rectum.

BACKGROUND AND OBJECTIVES: Clinicopathological significance of colorectal mucinous carcinoma (MC) remains controversial. The aim of the current study was to investigate the clinicopathological characteristics of colorectal MC. METHODS: Eighteen patients with MC and 265 with moderately or well differentiated adenocarcinoma of the colon and rectum, were clinicopathologically compared. RESULTS: MCs occurred in the right colon significantly more frequently than did non-mucinous carcinomas (NMCs). The maximal size of the tumors in MCs (7.0 +/- 2.9 cm) was significantly larger than that in NMCs (5.1 +/- 2.1 cm) (P < 0.001). Although the ratio of patients with peritoneal metastasis in MCs (22.2%; 4/18) was significantly higher than that in NMCs (6.0%; 16/265) (P < 0.05), there was no significant difference regarding liver metastasis. The proportion of lymph node metastasis in MCs (72.2%; 13/18) was significantly higher than that in NMCs (44.9%; 119/265) (P < 0.05). There was no significant difference regarding the lymphatic and venous invasion. The 1-, 3-, and 5-year survival rates of patients with MCs were 77. 8%, 45.4%, and 30.3%, respectively, and were significantly lower than those in patients with NMCs, that were 88.9 %, 65.6%, and 60.8%, respectively (P < 0.05). CONCLUSIONS: As colorectal MCs proliferate and metastasize more rapidly than do NMCs, surgeons should realize that more aggressive surgical treatment should be occasionally administered to improve the postoperative prognosis of the patients with colorectal MCs.

Adenocarcinoma, Mucinous↗

PubMed2000

Increased urinary nitrate excretion associated with hepatic allograft rejection in experimental rat models and clinical cases.

In this study, we investigated the relationship between excretion of urinary nitrate as a stable end-product of nitric oxide (NO) metabolism and hepatic allograft rejection. In experimental rat models, hepatic allograft rejection was associated with increased nitrate excretion with a peak on postoperative day 5. The severity of the hepatic allograft rejection was dependent on the increased urinary nitrate excretion. No significant increase in urinary nitrate excretion was observed in cases in which effective immunosuppression was achieved. Inducible nitric oxide synthase mRNA expression was upregulated parallel to interferon-gamma gene expression in the graft-infiltrating mononuclear cells and spleen cells from the recipients. In clinical cases, urinary nitrate excretion increased parallel to increased serum cytosolic enzymes that accompanied rejection. These results suggest that urinary nitrate excretion is a useful indicator for the surveillance of graft rejection and the monitoring of therapeutic effects of antirejection treatments.

Animals↗

PubMed2000

A new surgical strategy for cirrhotic patients with hepatocellular carcinoma and hypersplenism. Performing a hepatectomy after a laparoscopic splenectomy.

BACKGROUND: Hepatectomy for cirrhotic patients with hypersplenism is a high-risk operative procedure. We report herein a new strategy for high-risk patients with hepatocellular carcinoma (HCC). METHODS: Six cirrhotic patients with HCC and hypersplenism received a partial hepatectomy after first undergoing a laparoscopic splenectomy. We then compared the variables for these patients before splenectomy and before hepatectomy. RESULTS: The platelet count and the white blood cell count were found to be significantly elevated before hepatectomy. The ammonia value decreased significantly before hepatectomy. The albumin value tended to be elevated before hepatectomy. Furthermore, the Child's classification of all patients improved significantly before hepatectomy. However, other variables-such as the indocyanine green dye excretion test at 15 min and the bilirubin value-did not change after splenectomy. For hepatectomy patients who first underwent a laparoscopic splenectomy, operation time ranged from 265 to 440 min (average time, 361 min), and blood loss ranged from 500 to 2,200 ml (median volume, 1,300 ml). Four of six patients did not require any blood transfusion; furthermore, no patient needed a platelet-rich plasma transfusion. All but one patient, who suffered postoperatively from an intractable duodenal ulcer, had an uneventful postoperative course. CONCLUSION: Partial hepatectomy after an initial laparoscopic splenectomy is a new and effective choice of treatment for cirrhotic patients with HCC and hypersplenism.

Aged↗

PubMed2000

Laparoscopic hepatectomy: new approach for hepatocellular carcinoma.

This article presents the rationale for the laparoscopic approach to liver surgery, showing the technique of fully endoscopic and endoscopic-assisted formal and wedge hepatic resections. The early results are comparable to those of conventional surgery, with the benefits derived from minimal access surgery. Laparoscopic liver resections are technically feasible, with an acceptable morbidity and mortality rate, but extensive experience in conventional liver surgery, advanced laparoscopic surgery, and the availability of all requested technologies are indispensable prerequisites.

Carcinoma, Hepatocellular↗

PubMed2000

Rib metastasis appearing 8 years after surgery for lung cancer: report of a case.

A 39-year-old man underwent a right upper lobectomy and lymph node dissection for right lung adenocarcinoma on March 7, 1988. He was referred for an evaluation of a systemic bone scintillation scan on October 29, 1996. A hot spot at the right fourth rib was recognized. After performing needle aspiration cytology, a diagnosis of adenocarcinoma was made. This case was considered to be rib metastasis occurring 8 years after surgery for lung cancer. In general, regular follow-up examinations are performed for at least 5 years after surgery; however, surgeons should also keep such late metastatic cases in mind.

Adenocarcinoma↗

PubMed2000

A phase II trial of a new 5-fluorouracil derivative, BOF-A2 (Emitefur), for patients with advanced gastric cancer.

The antineoplastic effects of BOF-A2 (Emitefur), a 5-fluorouracil (5-FU) derivative, in capsule form were assessed in patients with advanced gastric cancer, in a multicenter late phase II study and at 11 different hospitals. The patients were scheduled to receive a minimum of two courses of BOF-A2 orally, with each course of BOF-A2 consisting of 200 mg twice daily for 2 weeks followed by a withdrawal period of 2 weeks. Of the 24 patients entered into the study, the clinical response was able to be evaluated in 21 cases and the toxicity was determined in 23 cases. Eleven (45.8%) patients had been treated previously with other anticancer drugs. There was a 38.1% (8/21) response rate (95% confidence interval 17.3-58.9) with 1 (4.8%) complete response (CR) and 7 (33.3%) partial responses (PR), and these responses continued for over 4 months. In particular, the response rate for the primary lesion was 33.3% (3/9). No change (NC) in the disease was observed in 5 (23.8%) patients, and in 8 (38.1%) the disease progressed (PD). At the time of analysis, the median survival of the responders was 13 months, while that of the NC group was 7 months and that of the PD group was 2 months. The major adverse events consisted of gastrointestinal symptoms, myelosuppression, and skin symptoms, while toxicities of grade 3 or more occurred in 26.1% (6/23). These toxicities all resolved within 1-37 days after discontinuing the drug treatment. Based on the above findings, BOF-A2 is considered to be a promising anticancer drug for patients with advanced gastric cancer.

Administration, Oral↗

PubMed2000

Effect of liver transplantation in a twin for biliary atresia on physical development and intellectual performance: report of a case.

A case of twins, one of whom suffered from biliary atresia, is described herein. Although the patient had been doing well until 11 years of age after previously undergoing a primary hepatic portoenterostomy, she had to then undergo a liver transplantation due to severe refractory cholangitis at 14 years of age. Although the patient's intellectual performance had severely declined due to the progression of her illness for several years, it completely recovered after the liver transplantation. In cases where the physical development in childhood has been well preserved, liver transplantation might therefore offer the chance for a full recovery of deteriorated intellectual performance.

Biliary Atresia↗

PubMed2000

Hepatic sclerosing hemangioma mimicking a metastatic liver tumor: report of a case.

We present herein the case of a sclerosing hemangioma of the liver which was extremely difficult to differentiate from liver metastasis of rectal cancer, in a 67-year-old woman. All the radiological findings were compatible with liver metastasis; however, marginal pooling of the tumor revealed by computed tomographic angiography and magnetic resonance imaging scans was inconsistent with a diagnosis of liver metastasis. At laparotomy, the tumor was macroscopically unusual in that it was yellowish elastic-hard with a very clear margin, and thus, it did not have the appearance of a metastatic tumor. Mile's operation and a partial hepatectomy were performed, followed by an uneventful postoperative course and no signs of recurrence. The carcinoembryonic antigen (CEA) level in the peripheral blood was not elevated at any time. The postoperative pathological diagnosis was a rare hepatic tumor, namely, a "sclerosing hemangioma," based on the findings of cellular fibrous stroma containing vascular channels with flattened endothelial cells. Preoperatively differentiating between sclerosing hemangioma and a metastatic liver tumor from colorectal cancer may be very difficult; however, this case demonstrated some interesting characteristics, namely, the serum CEA level was not elevated, marginal pooling of the tumor was found in the enhanced radiological findings, and the tumor was macroscopically unusual. Therefore, the possibility of sclerosing hemangioma should be borne in mind when considering the differential diagnosis of patients suspected of having colorectal liver metastasis. A preoperative biopsy should be carried out and when a laparotomy is performed under the misdiagnosis of colorectal liver metastasis, it is advisable that either an intraoperative needle biopsy or a frozen histological analysis be undertaken to avoid unnecessary extended hepatic resection of this rare benign hepatic tumor.

Aged↗

PubMed2000

Analysis of the genetic alterations in a case of juvenile multiple colon carcinoma with hypogammaglobulinemia.

BACKGROUND: We have previously reported the clinical characterization of a case of juvenile multiple colorectal carcinoma with hypogammaglobulinemia. Several recent studies have determined that agammaglobulinemia was caused by the loss of Bruton's tyrosine kinase (Btk) function. However, any genetic alterations associated with carcinoma formation in individuals with this immunodeficient disease have not been reported. METHODS: DNA from eight carcinoma tissues and nine adenoma tissues from this reported case were examined for mutations in p53 by single strand conformation polymorphism analysis, K-ras by mutant allele specific analysis, and replication error or loss of heterozygosity of the TP53 locus on chromosome #17. RESULTS: We found that p53 and K-ras were mutated in the carcinoma tissues. However, each tumor showed unequal and diverse results. CONCLUSIONS: The progression of individual tumor was not due to a common genetic event caused directly under the influence of the primary disease at the genetic level.

Adenoma↗

PubMed2000

Direct IFNluence of interferon-gamma on proliferation and cell-surface antigen expression of non-small cell lung cancer cells.

In order to clarify the anti-tumor activity of IFN-gamma, we investigated the direct IFNluence of IFN-gamma on both the growth and cell-surface antigen expression of tumor cells. In the present study, four human lung cancer cell lines were used; two squamous cell lines (QG-56, QG-95) and two adenocarcinoma cell lines (PC-9, PC-12). In all four tumor cell lines, mutations were detected in exon 7 of the p53 gene by a PCR-FSSCP analysis. The proliferation of QG-56 or QG-95 was inhibited by IFN-gamma in a dose-dependent manner with about 70% inhibition at 1000 JRU/ml while that of PC-9 was slightly inhibited with maximally 25% inhibition at 1000 JRU/ml. The growth of PC-12 was not inhibited at all. In QG-56, QG-95 and PC-9, the fraction of cells in G1 phase increased while the fractions of cells in both S and G2/M phases decreased after exposure to IFN-gamma (200 JRU/ml) for 72 h. The growth inhibition by long-term exposure to IFN-gamma was irreversible in QG-56. After culture in the presence of IFN-gamma (200 JRU/ml) for 14-16 days, tumor cells were examined for expression of various antigens, including HLA-class I, HLA-class II, and CEA. In all cell lines but PC-12, 100% of cells expressed HLA-class I after incubation with IFN-gamma. Both HLA-class II and CEA were also induced in those cell lines. The proportion of HLA-class II-positive cells or that of CEA-positive cells varied among the cell lines. Of the three antigens, the degree of HLA-class II expression paralleled that of growth inhibition by IFN-gamma treatment. These results suggested that in various function of IFN-gamma against tumor cells, the anti-proliferative effect might be closely linked with the induction of HLA-class II probably through a similar posttranscriptional process, independent of the function of p53 gene.

Antigens, Surface↗