Biomedical subjects

M Ikeguchi

Publications and source records attributed to M Ikeguchi.

At least 55 records · Page 3Linked to original sources

PubMed1999

The expression of transforming growth factor-beta1 is significantly correlated with the expression of vascular endothelial growth factor and poor prognosis of patients with advanced gastric carcinoma.

BACKGROUND: Transforming growth factors beta (TGFs beta) are involved in a variety of important cellular functions, including cell growth and differentiation, adhesion, migration, extracellular matrix formation, and immune function. Moreover, it has been reported that TGFs beta are correlated with angiogenesis. However, the role of TGF-beta as an angiogenic factor in gastric carcinoma is still unclear. METHODS: TGF-beta1 expression was determined in 101 patients with gastric carcinoma by immunohistochemical procedures, and this expression was compared in the current study with both the expression of vascular endothelial growth factor (VEGF), which is thought to be the most potent angiogenic factor, and microvessel density, to evaluate the effect of TGF-beta1 on the angiogenesis of gastric carcinoma tissues. RESULTS: TGF-beta1 expression was detected in 23 tumors (22.8%). TGF-beta1 expression was more frequent in differentiated than in undifferentiated gastric carcinoma. Furthermore, TGF-beta1 expression was significantly correlated with the depth of invasion and the stage of disease. There was a close correlation between TGF-beta1 expression and VEGF expression. There was no correlation between TGF-beta1 expression and microvessel density, whereas VEGF expression was significantly correlated with microvessel density. With regard to prognosis, the 5-year survival rate was 55.9% for patients with TGF-beta1 positive tumors and 67.0% in patients with TGF-beta1 negative tumors. Accordingly, the prognosis for patients with TGF-beta1 negative tumors was significantly better than that for patients with TGF-beta1 positive tumors. Multivariate analysis indicated that lymph node metastasis, tumor size, and TGF-beta1 expression were independent prognostic factors. CONCLUSIONS: These results suggest that TGF-beta1 might be associated with tumor progression by indirectly stimulating angiogenesis through the up-regulation of VEGF expression in gastric carcinoma.

Adenocarcinoma↗

PubMed1999

Clinical significance of spontaneous apoptosis in advanced gastric adenocarcinoma.

BACKGROUND: Spontaneous apoptosis has been detected in gastric carcinoma. However, the clinicopathological significance of this remains unclear. The objective of this study was to investigate the correlation between spontaneous apoptosis and the clinicopathologic and biologic characteristics of advanced gastric carcinoma. In addition, the prognostic significance of spontaneous apoptosis of tumors was evaluated. METHODS: The occurrence of apoptotic cell death (apoptotic index [AI]) in 97 patients with advanced gastric carcinoma was analyzed by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate biotin nick end labeling method. The Ki-67 labeling index (LI), expression of p53 and p21, DNA ploidy pattern, microvessel density (MVD), density of dendritic cells (DCs) in tumors, and degree of lymphocytic infiltration (LI) of the tumors were compared with the AI for each patient. In addition, the prognostic significance of AI was evaluated in these patients. RESULTS: The mean AI of the 97 tumors was 2.05% (range, 0-11.31%). Statistical analyses revealed significant correlations between the AIs and the Ki-67 LIs (P = 0.0004) and between the AIs and the density of DCs (P = 0.0007), as well as an inverse correlation between the AIs and the intratumoral MVD (P = 0.0064). In addition, the AI of 47 tumors with high grade LI (2.94+/-2.51%) was significantly higher than that of 50 tumors with low grade LI (1.22+/-0.93%) (P<0.0001). However, the authors failed to find a significant correlation between the AIs and expression of p53 and p21 and the DNA ploidy pattern. In 93 surviving patients, the 5-year survival rate of 45 patients who had tumors with high AIs (> or =1.47; 82%) was significantly better than that of 48 patients who had tumors with low AIs (<1.47; 60%) (P = 0.0264). CONCLUSIONS: The findings of the current study suggest that the tumors with low neovascularization and high local immunoreactivity may regulate their progression by apoptosis. Moreover, less extensive apoptosis in gastric adenocarcinoma may contribute to disease progression and could be correlated with a poorer prognosis.

Adenocarcinoma↗

PubMed1999

Molecular and enzymic properties of recombinant 1, 2-alpha-mannosidase from Aspergillus saitoi overexpressed in Aspergillus oryzae cells.

For the construction of an overexpression system of the intracellular 1,2-alpha-mannosidase (EC 3.2.1.113) gene (msdS) from Aspergillus saitoi (now designated Aspergillus phoenicis), the N-terminal signal sequence of the gene was replaced with that of the aspergillopepsin I (EC 3.4.23.18) gene (apnS) signal, one of the same strains as described previously. Then the fused 1, 2-alpha-mannosidase gene (f-msdS) was inserted into the NotI site between P-No8142 and T-agdA in the plasmid pNAN 8142 (9.5 kbp) and thus the Aspergillus oryzae expression plasmid pNAN-AM1 (11.2 kbp) was constructed. The fused f-msdS gene has been overexpressed in a transformant A. oryzae niaD AM1 cell. The recombinant enzyme expressed in A. oryzae cells was purified to homogeneity in two steps. The system is capable of making as much as about 320 mg of the enzyme/litre of culture. The recombinant enzyme has activity with methyl-2-O-alpha-d-mannopyranosyl alpha-D-mannopyranoside at pH 5.0, while no activity was determined with methyl-3-O-alpha-D-mannopyranosyl alpha-D-mannopyranoside or methyl-6-O-alpha-D-mannopyranosyl alpha-D-mannopyranoside. The substrate specificity of the enzyme was analysed by using pyridylaminated (PA)-oligomannose-type sugar chains, Man9-6(GlcNAc)2-PA (Man is mannose; GlcNAc is N-acetylglucosamine). The enzyme hydrolysed Man8GlcNAc2-PA (type 'M8A') fastest, and 'M6C' {Manalpha1-3[Manalpha1-2Manalpha1-3(Manalpha1-6) Manalpha1-6]Manbeta1- 4GlcNAcbeta1-4GlcNAc-PA} slowest, among the PA-sugar chains. Molecular-mass values of the enzyme were determined to be 63 kDa by SDS/PAGE and 65 kDa by gel filtration on Superose 12 respectively. The pI value of the enzyme was 4.6. The N-terminal amino acid sequence of the enzyme was GSTQSRADAIKAAFSHAWDGYLQY, and sequence analysis indicated that the signal peptide from apnS gene was removed. The molar absorption coefficient, epsilon, at 280 nm was determined as 91539 M-1.cm-1. Contents of the secondary structure (alpha-helix, beta-structure and the remainder of the enzyme) by far-UV CD determination were about 55, 38 and 7% respectively. The melting temperature, Tm, of the enzyme was 71 degrees C by differential scanning calorimetry. The calorimetric enthalpy, DeltaHcal, of the enzyme was calculated as 13.3 kJ.kg of protein-1. Determination of 1 g-atom of Ca2+/mol of enzyme was performed by atomic-absorption spectrophotometry.

Amino Acid Sequence↗

PubMed1999

Folding-unfolding equilibrium and kinetics of equine beta-lactoglobulin: equivalence between the equilibrium molten globule state and a burst-phase folding intermediate.

The denaturant-induced equilibrium unfolding transition of equine beta-lactoglobulin was investigated by ultraviolet absorption, fluorescence, and circular dichroism (CD) spectra. An equilibrium intermediate populates at moderate denaturant concentrations, and its CD spectrum is similar to that of the molten globule state previously observed for this protein at acid pH [Ikeguchi, M., Kato, S., Shimizu, A., and Sugai, S. (1997) Proteins: Struct., Funct., Genet. 27, 567-575]. The unfolding and refolding kinetics were also investigated by the stopped-flow CD and fluorescence. A significant change in the CD intensity was observed within the dead time of measurements (25 ms) when the refolding reaction was initiated by diluting the urea-unfolded protein solution, indicating the transient accumulation of the folding intermediate. The CD spectrum of this burst-phase intermediate agrees well with that of the molten globule state at acid pH. The stability of the burst-phase intermediate was also estimated from the urea-concentration dependence of the burst-phase amplitude, and it shows a fair agreement with that of the equilibrium intermediate. These results indicate that the molten globule state of equine beta-lactoglobulin populates at moderate urea concentration as well as at acid pH and it is equivalent with the kinetic folding intermediate.

Animals↗

PubMed1999

The expression of vascular endothelial growth factor and proliferative activity of cancer cells in gastric cancer.

BACKGROUND/AIMS: Vascular endothelial growth factor (VEGF) is one of the most important factors for angiogenesis in various malignant tumors. However, the clinicopathological and biological significance of the expression of VEGF in gastric cancer remains unclear. In this study, we investigated the relationship between the expression of VEGF and the clinicopathological and biological status of advanced gastric cancer, all of the same stage. PATIENTS/METHODS: The expression of VEGF was immunohistochemically examined using the polyclonal antibody A-20 in tumors from 97 patients with invasion of the serosa but no lymph-node metastasis (t3, n0, stage II). The results were compared with clinicopathological and biological status (microvessel density and proliferative activity) of tumors. RESULTS: Expression of VEGF was detected in 27 of 97 tumors (28%). The mean microvessel density (MVD) of 27 VEGF-positive tumors (458/mm2) was higher than that of 70 VEGF-negative tumors (331/mm2, P=0.0001). However, the proliferative activity expressed as the Ki-67 labeling index (LI; percentage of immunostained cancer cells) of 27 VEGF-positive tumors (13.8%) was significantly lower than that of 70 VEGF-negative tumors (26.7%, P=0.0002). In 48 tumors with low proliferative activity of cancer cells (Ki-67 LI < or =18%), 20 (42%) tumors expressed VEGF, and these tumors had a high MVD (4461/mm2). In the 93 surviving patients, the 5-year survival rate of the 25 patients with VEGF-positive tumors (64%) was not different from that of the 68 patients with VEGF-negative tumors (73%, P=0.4296). CONCLUSION: Advanced gastric carcinoma with low proliferative activity may produce VEGF and may have high angiogenic potential in order for the tumor itself to grow. However, the prognosis of patients with such tumors was not unfavorable.

Adult↗

PubMed1999

Detection of telomerase activity in esophageal squamous cell carcinoma and normal esophageal epithelium.

BACKGROUND/AIMS: Relatively little has been reported about the telomerase activity of esophageal squamous cell carcinoma or normal esophageal epithelium. In this study, we have evaluated whether telomerase activity is a useful marker for detecting malignancies in the esophagus. PATIENTS/METHODS: Esophageal carcinomas and normal esophageal tissues adjacent to carcinomas were obtained from 52 surgically treated, unselected patients, and normal esophageal epithelium from 11 non-cancerous patients were obtained by means of biopsy. The telomeric repeat amplification protocol (TRAP) assay was used for detection of telomerase activity in these samples. The incidence of detection of telomerase activity in esophageal carcinoma was compared with that of telomerase activity in normal esophageal epithelium. Moreover, the clinicopathological characteristics of telomerase-positive tumors were compared with those of telomerase-negative tumors. RESULTS: Of the 52 carcinomas, 40 (77%) had detectable telomerase activity. However, telomerase activity was detected in 45 of 52 (87%) normal tissue samples adjacent to carcinomas and in 8 of 11 (73%) normal esophageal epithelium from non-cancerous patients. In esophageal cancer, no significant difference was detected in the clinicopathological findings between the telomerase-positive and -negative cases. CONCLUSION: These results indicate that not only esophageal squamous cell carcinomas but also normal esophageal epithelium show strong telomerase activity. Thus, telomerase activity may not be a good marker for the detection of carcinoma in the esophagus.

Aged↗

PubMed1999

The expression of thymidine phosphorylase correlates with angiogenesis and the efficacy of chemotherapy using fluorouracil derivatives in advanced gastric carcinoma.

The expression of thymidine phosphorylase (TP) and the density of microvessel in advanced gastric carcinoma were examined by immunohistochemistry to evaluate the significance of TP. The expression of TP was negative in 72 cases, positive in 54. The microvessel density correlated with the expression of TP. In total cases, patients with TP-positive tumours survived longer than those with TP-negative tumours. In patients treated with fluorouracil derivatives (FUs), the expression of TP significantly correlated with favourable prognosis and with unfavourable prognosis in those not treated with FUs. The patients with TP-positive tumours, the prognosis of patients treated with FUs was significantly better than that of those not treated with FUs. In patients with TP-positive tumours, treatment with FUs and lymph node metastasis were independent prognostic factors according to the Cox proportional hazards model. Depth of invasion and lymph node metastasis were independent prognostic factors in patients with TP-negative tumours. The determination of the expression of TP might be useful for predicting the efficacy of post-operative chemotherapy using FUs to prevent recurrence in advanced gastric carcinoma patients who undergo curative gastrectomy.

Adenocarcinoma↗

PubMed1999

Computerized nuclear morphometry: a new morphologic assessment for advanced gastric adenocarcinoma.

OBJECTIVE: To evaluate the correlation between the morphologic nuclear features and clinicopathologic parameters in patients with advanced gastric cancer. SUMMARY BACKGROUND DATA: Nuclear profiles have been reported as useful prognostic predictors in various cancers. Data from computerized morphometries are objective and quickly derived using conventional microscopic analysis. However, this image analysis of nuclear features has rarely been applied to investigations of gastric adenocarcinoma. Moreover, it remains to be shown what types of biologic factors influence the nuclear features. METHODS: Morphometric nuclear features (nuclear area, perimeter, and shape) were analyzed in 202 patients with serosal-invaded gastric cancer (stage II and III) who underwent curative gastrectomy. In each case, 300 cancer nuclei were analyzed on routine hematoxylin and eosin-stained slides through the use of a computer-assisted image analysis system by tracing the nuclear profiles (magnification x400) on a computer monitor. The morphometric data were compared with patient survival, clinicopathologic status, DNA ploidy pattern of tumors, expression of p53 protein, and proliferative activity of cancer cells. RESULTS: Lymph node metastasis, lymphatic invasion, and venous invasion were more frequently detected in patients with large nuclear areas. Significant correlations were detected between the size of the nuclear area of cancer cells and the biologic factors of tumors, such as expression of p53, Ki-67 labeling index, and DNA ploidy pattern. The 5-year survival rate of the 100 patients in the large-nuclear group (nuclear area >45.3 microm2) was 47.6% and was significantly lower than the 74.4% rate of the 98 patients in the small-nuclear group (nuclear area < or =45.3 microm2). Moreover, the nuclear area was found to be an independent prognostic factor in the multivariate analysis. CONCLUSIONS: Gastric cancer cells with a large nuclear area express mutated p53 protein and have high proliferative activity. Moreover, such cancer cells have high potential for invasion to the microvessels in the gastric wall. Thus, nuclear morphometry is a new and useful morphologic predictor for metastatic potential in advanced gastric cancer.

Adenocarcinoma↗

PubMed1999

Clinical significance of the detection of thymidine phosphorylase activity in esophageal squamous cell carcinomas.

In this study, we obtained fresh samples of tissue (tumors, adjacent normal mucosas, and metastatic lymph nodes) from 64 patients (metastatic lymph nodes were obtained from 16 patients) with esophageal cancer who underwent esophagectomy between 1993 and 1998. The thymidine phosphorylase (dThdPase) levels of tumors as determined by the ELISA method were compared with clinicopathological findings of tumors and were evaluated for their usefulness as a prognostic parameter for these patients. The dThdPase levels of tumors (221 +/- 21 U/mg protein) and metastatic lymph nodes (253 +/- 51 U/mg protein) were significantly higher than the dThdPase level of normal mucosas (53 +/- 7 U/mg protein, p < 0. 001). The dThdPase levels of tumors did not correlate with the histopathological grading of tumors, the depth of tumor invasion, and lymph node metastasis. The 3-year survival rate of 32 patients with a high level of dThdPase (42%) was not different from that of 32 patients with a low level of dThdPase (52%, p = 0.267). Moreover, the dThdPase level of tumors was not an independent prognostic factor for patients with esophageal cancer. These findings suggest that the level of dThdPase activity in esophageal cancers may not correlate with tumor progression and may not be a useful prognostic marker for patients with esophageal squamous cell carcinoma.

Aged↗

PubMed1999

Detection of loss of heterozygosityat microsatellite loci in esophageal squamous-cell carcinoma.

Microsatellite alterations at 3 genetic loci (chromosomes 2p, 3p and 17p) were analyzed in 25 tumors (20 primary tumors and 5 metastatic lymph nodes) from 20 patients after surgical treatment for esophageal cancer. DNA samples from tumors were compared with control DNA from lymphocytes obtained from the peripheral blood of the individual patients. Microsatellite alterations [microsatellite instability (MSI) and loss of heterozygosity (LOH)] were detected in 15% of 20 primary tumors with marker D2S123 (chromosome 2p), 55% with marker D3S1067 (chromosome 3p) and 50% with marker TP53 (chromosome 17p). The 3-year disease-free survival rate of the 10 patients who had tumors without alterations or with an alteration at only 1 of 3 microsatellite loci was 75% and it was better than that of the 10 patients who had tumors with alterations at 2 or 3 microsatellite loci (48%, p = 0.049). This finding suggests that esophageal cancer with alterations at multiple microsatellite loci might have strong malignant potential. However, MSI was only detected in one of 20 patients, which suggests that MSI might not play an important role in the development of this cancer. Three of 5 metastatic lymph nodes showed no LOH even though primary tumors of these patients exhibited LOH with 1 or 2 markers, and 1 metastatic lymph node had LOH that was detected with D3S1067 even though the primary tumor of this patient had no LOH with all markers. Thus, clonal heterogeneity might exist in esophageal squamous-cell carcinomas.

Aged↗

PubMed1999

Serum level of a soluble receptor for interleukin-2 as a prognostic factor in patients with gastric cancer.

Increased levels of a soluble receptor for interleukin-2 (sIL-2R) have been found in the serum from patients with a variety of malignancies. Levels of sIL-2R have not previously been examined in a large group of patients with gastric cancer as a possible indicator of prognosis. Serum levels of sIL-2R were measured preoperatively by an enzyme-linked immunosorbent assay in 121 patients with gastric cancer. The preoperative levels of sIL-2R in patients with gastric cancer were significantly higher than those in normal controls. An elevated level of sIL-2R was significantly correlated with certain clinicopathologic features, which included depth of invasion, lymph node metastasis, lymphatic vessel invasion, blood vessel invasion and clinical stage. The postoperative survival time of patients with elevated levels of sIL-2R was significantly shorter than that of patients with normal levels. Furthermore, a multivariate analysis using Cox's proportional hazards model showed that the combination of levels of carcinoembryonic antigen and sIL-2R was an independent indicator of prognosis. Thus, the serum level of sIL-2R might be a useful prognostic indicator in patients with gastric cancer.

Adenocarcinoma↗

PubMed1999

Administration in a hypotonic solution is preferable to dose escalation in intraperitoneal cisplatin chemotherapy for peritoneal carcinomatosis in rats.

An animal model of intraperitoneal (i.p.) cisplatin chemotherapy using hypotonic solutions of sodium chloride has been developed as a treatment for peritoneal carcinomatosis. The concentrations of platinum in the plasma and in the i.p. fluid of Donryu rats were measured after i.p. injection of hypotonic (103 or 154 mosm/l) and isotonic (308 mosm/l) solutions that contained an equal amount of cisplatin. The maximum concentration (Cmax) and the area under the curve of concentration versus time (AUC) of platinum in the plasma increased proportionately with increases in the dose of cisplatin and they were significantly higher in rats given cisplatin in hypotonic solutions than in those given the drug in isotonic solution. The Cmax and AUC of total platinum were similar for the solution of 103 mosm/l with 2.5 mg/kg cisplatin and the isotonic solution with 5.0 mg/kg cisplatin. The Cmax and AUC of free platinum in the plasma did not increase with increases in the dose of cisplatin in isotonic solution but did increase after hypotonic injection. However, the solutions of lower osmolarity gave a decreased AUC of platinum in the i.p. fluid. Hypotonic conditions continued for 30 min at most after i.p. injection of hypotonic solutions. When the same dose of cisplatin was given to rats with tumors derived from AH100B carcinoma cells, the amount of platinum taken by i.p. solid tumors from the solution of 103 mosm/l was about twice that from the isotonic solution and was much the same as that taken up from the isotonic solution with twice the amount of cisplatin. These results indicate that hypotonic i.p. cisplatin chemotherapy might be preferable to escalation of the dose of i.p. cisplatin in the treatment of peritoneal carcinomatosis.

Animals↗

PubMed1999

Neoangiogenesis and relationship to nuclear p53 accumulation and vascular endothelial growth factor expression in advanced gastric carcinoma.

Recent studies have shown that tumor suppressor genes, particularly p53, may play a crucial regulatory role in the control of angiogenesis. Accordingly, we analyzed the correlation between p53 accumulation and the expression of vascular endothelial growth factor (VEGF) and microvessel counts in a series of human gastric adenocarcinomas by immunohistochemical staining. p53 expression was absent in 35 cases (29.7%), weak in 34 cases (28.8%), moderate in 35 cases (29.7%), and strong in 14 cases (11.8%). The prognosis of patients with both absent and weak expression of p53 was significantly better than that of patients with both moderate and strong expression of p53. VEGF expression was significantly associated with increased p53 expression. Moreover, increasing expression of p53 significantly correlated with an increase in microvessel counts. Nuclear p53 accumulation may correlate with tumor angiogenesis through VEGF upregulation in gastric carcinomas.

Adenocarcinoma↗

PubMed1999

Less invasive surgery for early gastric cancer based on the low probability of lymph node metastasis.

BACKGROUND: Less invasive treatment is the current trend in many surgical fields. Most patients with early gastric cancer do not have lymph node metastasis. Thus extensive resection of the stomach and extended lymph node dissection do not appear to be necessary. METHODS: In a retrospective study, 890 consecutive patients with early gastric cancer who had undergone standard gastrectomy were assessed for depth of invasion, gross appearance, and maximum diameter of the tumor to examine the possibility of limiting the extent of lymph node dissection. A variety of limited gastrectomies have been developed and now include endoscopic mucosal resection, wedge resection, segmental gastrectomy, limited proximal gastrectomy, and distal hemigastrectomy. RESULTS: A retrospective study revealed that extensive lymph node dissection did not improve the survival of patients with early gastric cancer. Endoscopic mucosal resection was suitable for cancers of the depressed type of less than 1 cm in diameter and the elevated type of less than 2 cm in diameter. Wedge, segmental, or limited proximal gastrectomy was suitable for the elevated type of 2 to 3 cm in diameter. The elevated type of more than 3 cm in diameter and the depressed type of 1 to 3 cm in diameter sometimes involved metastasis to group 1 nodes. The depressed type of more than 3 cm in diameter sometimes involved metastasis to group 2 nodes. Thus such cases should be treated by gastrectomy with dissection of potentially metastatic lymph nodes. CONCLUSIONS: Limitation of the extent of gastrectomy and lymph node dissection may be possible, depending on the gross appearance and size of the tumor.

Adult↗

PubMed1999

Expression of vascular endothelial growth factor correlates with hematogenous recurrence in gastric carcinoma.

BACKGROUND: It has recently been reported that the microvessel density in a tumor correlates with hematogenous metastasis in gastric carcinoma. The aim of this study was to evaluate the relationship between the expression of vascular endothelial growth factor (VEGF), which was thought to be a potent angiogenesis-promoting factor, and hematogenous recurrence in advanced gastric carcinoma. METHODS: The expression of VEGF and the density of the microvessels were examined by immunohistochemistry in patients with advanced gastric carcinoma with serosal invasion who had undergone curative resection. RESULTS: The prognosis of patients with a VEGF-negative tumor was significantly better than that of patients with a VEGF-positive tumor. Multivariate analysis by Cox proportional hazards model showed that the expression of VEGF was an independent prognostic indicator. The expression of VEGF provided a significant estimate of relative risk for the development of hematogenous recurrence by multivariate logistic regression analysis. The microvessel count in VEGF-positive tumors was significantly higher than that in VEGF-negative tumors. CONCLUSIONS: VEGF is associated with hematogenous recurrence. Assessment of the expression of VEGF may therefore prove valuable in identifying patients with gastric carcinoma at high risk for recurrence who would benefit from adjuvant therapy.

Adult↗

PubMed1999

A prospective pilot study of extended (D3) and superextended para-aortic lymphadenectomy (D4) in patients with T3 or T4 gastric cancer managed by total gastrectomy.

BACKGROUND: Japanese surgeons have been actively performing extended lymphadenectomy (D2, removal of perigastric nodes and nodes along the left gastric, common hepatic, celiac and splenic arteries; or D3, D2 plus removal of nodes in the hepatoduodenal ligament, in the retropancreatic space and along the vessels of the transverse mesocolon). In recent years interest has expanded to superextended lymphadenectomy (D4) of nodes around abdominal aorta (para-aortic lymph nodes from aortic hiatus to aortic bifurcation). Because the therapeutic value of this D4 procedure remains controversial, we initiated a prospective study to compare D3 and D4 lymphadenectomy. METHODS: Seventy patients with T3 or T4 gastric cancer and without macroscopic metastasis to the para-aortic nodes treated by potentially curative total gastrectomy were randomized to D4 (group A, n = 35) and D3 (group B, n = 35) lymphadenectomies. RESULTS: Metastases to para-aortic nodes were found in 4 patients. Postoperative survival after D4 resection was not statistically significant between the groups. Postoperative morbidity for group A was greater. In group A 4 patients had postoperative retention of intra-abdominal fluid (lymphorrhea) and 4 others had prolonged diarrhea. One patient in each group died of postoperative complications. CONCLUSIONS: Surgical treatment of microscopic disease in grossly normal para-aortic lymph nodes may generate occasional long-term survivors. Selecting appropriate candidates who might benefit from D4 resections needs to be refined. On the basis of this study, a nationwide study should be considered.

Aged↗

PubMed1998

Serum concentration of CD44 variant 6 and its relation to prognosis in patients with gastric carcinoma.

BACKGROUND: The expression of variant isoforms of CD44 is correlated with the ability of tumor cells to metastasize in some clinical carcinomas. In this study, the serum concentration of soluble splice isoforms of CD44 that shared exon variant 6 (sCD44v6) were measured and the histologic expression of CD44v6 in tumors from patients with gastric carcinoma examined. METHODS: Serum samples were obtained from 102 patients with primary gastric carcinoma before surgery and serum levels of sCD44v6 were determined with an enzyme-linked immunoadsorbent assay. The expression of CD44v6 in tumors was examined by immunohistochemical staining. RESULTS: Both the serum concentration of sCD44v6 and its expression in tumors were associated significantly with the depth of invasion of the tumor, lymph node metastasis, and clinical stage in patients with diffuse type gastric carcinoma. Among patients with gastric carcinoma, the serum level of sCD44v6 was higher in those with CD44v6 positive tumor cells than in those with CD44v6 negative tumor cells. The serum level of sCD44v6 was a prognostic indicator in patients with diffuse type gastric carcinoma, as was the histologic expression of CD44v6. However, neither CD44v6 nor sCD44v6 was a predictor of survival time in patients with intestinal type gastric carcinoma. CONCLUSIONS: It appears that CD44v6 and sCD44v6 are related to the progression of diffuse type gastric carcinoma. An elevated serum level of sCD44v6 may be useful as a prognostic indicator in patients with diffuse type gastric carcinoma.

Adult↗

PubMed1998

The use of sequence comparison to detect 'identities' in tRNA genes.

We have developed a computational method that detects 'identities' in tRNA genes by using principal component analysis to classify the sequences of bases in tRNA genes into groups of similar sequences and then comparing the distribution of sequences of bases, in order to extract characteristic bases that are conserved within a group but differ between groups. These classification and comparison procedures are applied recursively to classify the sequences into hierarchical groups, so that multiple levels of characteristic sites can be detected. By using this computational method, we were able to detect many characteristic sites in the T and D domains of tRNAs, as well as the characteristic sites that had already been detected experimentally. This suggests that bases not only in the contact regions but also in the elbow regions, which determine the structure and dynamics of the whole tRNA molecule, are important to the tRNA-aminoacyl tRNA synthetase recognition.

Amino Acyl-tRNA Synthetases↗