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H Ueo

Publications and source records attributed to H Ueo.

At least 55 records · Page 3Linked to original sources
PubMed1996

Expression of BAGE, GAGE, and MAGE genes in human gastric carcinoma.

The MAGE, BAGE, and GAGE genes code for distinct antigens that are recognized by autologous cytolytic T lymphocytes. We investigated the expression of these genes in both cell lines and surgical samples of gastric carcinoma, using reverse transcription-PCR. Furthermore, the induction of these genes by 5-aza-2'-deoxycytidine (DAC), a demethylating agent, was also examined in several cell lines. Of 11 cell lines, BAGE, GAGE1-6, GAGE1-2, MAGE-1, and MAGE-3 were detected in 7 (64%), 4 (36%), 3 (27%), 8 (73%), and 8 (73%) cell lines, respectively. After the in vitro treatment of the negative cell lines with DAC, the expression of these genes became positive in 46 to 91% of these cell lines. No expression of these genes was seen in any of the 57 samples of normal gastric tissue. In contrast, the tumor tissue samples expressed BAGE, GAGE1-6, GAGE1-2, MAGE-1, and MAGE-3 in 13 (23%), 9 (16%), 6 (11%), 25 (44%), and 23 (40%) tissue samples, respectively. Thus, at least one of these genes was expressed in 35 (61%) of 57 carcinomas. An analysis of the relationship between clinicopathological factors and the expression of these genes revealed that either BAGE or one of these genes was more frequently expressed in histologically intestinal-type than in diffuse-type carcinomas. Our results suggest that, because of the higher expression of these genes and the possible induction of these genes by DAC, patients with gastric carcinoma may, therefore, be potential candidates for tumor-specific immunotherapy directed against these antigens.

Aged↗
PubMed1995

Microsatellite instability in multiple gastric cancers.

To better elucidate the role of genetic instability in the development of gastric cancer, microsatellite alterations were examined in a total of 30 gastric cancers that developed in 14 Japanese patients with multiple gastric cancers, which are considered to have possibly occurred under the same genetic background and in the same microenvironment of the stomach. Microsatellite instability (MSI) in multiple gastric cancers was recognized in 11 out of 14 cases (78.5%) and in 16 out of 30 cancers (53.3%). Eight out of 11 cases showing MSI exhibited a heterogeneity of microsatellite alterations. The incidence of microsatellite instability in the multiple gastric cancers cases was significantly higher than that in the solitary gastric cancer cases reported previously (20.8%: 5 out of 24 cases). These results suggested that (1) genetic instability plays a more important role in the development of multiple gastric cancers than in that of solitary gastric cancer and (2) the heterogeneity of MSI in multiple gastric cancers may not be a rare event, although the significance of the heterogeneity could not be clarified.

Adenoma↗
PubMed1995

Detection of cancer micrometastases in lymph nodes by reverse transcriptase-polymerase chain reaction.

There are few DNA-based studies that detect cancer micrometastases in lymph nodes. We have assayed for the specific detection of carcinoembryonic antigen (CEA)-expressing carcinoma cells in the lymph nodes of patients with gastrointestinal or breast carcinomas. A CEA-specific nested reverse transcriptase (RT)-PCR assay was optimized using limiting dilutions of a CEA-positive cancer cell line mixed with normal lymphocytes. The expression of CEA mRNA was studied in 100 carcinoma tissues, 75 normal mucosal tissues, and 15 lymph nodes from patients with cholelithiasis. Each of 117 lymph nodes from 13 patients with carcinoma was divided into two pieces: one was used for histological examination and the other for RT-PCR, and the results were compared. The sensitivity ratio was one CEA-expressing cancer cell detected in 1 x 10(5) normal lymphocytes. All carcinoma tissues and normal mucosal tissues expressed CEA mRNA, while no amplification was detected in any control lymph nodes. Thirty of 117 lymph nodes were histologically involved by carcinoma cells, and all of these yielded the expected product by RT-PCR. Of the remaining 87 histologically negative nodes, CEA mRNA was detected in 47 lymph nodes by RT-PCR. The positive rate increased from 26% by histological examination to 66% by RT-PCR. The assay by CEA-specific nested RT-PCR is not only sensitive but widely applicable for the detection of cancer micrometastases in lymph nodes. This method may lead to an earlier diagnosis and treatment of patients with subclinical lymph node metastasis.

Adult↗
PubMed1995

Microsatellite instability in Japanese gastric cancer.

BACKGROUND: Recent studies have shown that microsatellites are unstable in various types of cancers, and such genetic instability at the microsatellite loci (microsatellite instability) has been considered to play an important role in the development of cancer. However, the clinicopathologic significance of microsatellite instability in gastric cancer has not been clarified. METHODS: To elucidate the role of genetic instability in the development of gastric cancer, the presence of microsatellite instability was examined in 25 cases of gastric cancer using fresh-frozen tumor-normal paired samples using a polymerase chain reaction (PCR)-based method. Microsatellite instability was defined as tumors that showed altered banding patterns at two or more microsatellite loci. RESULTS: The incidence of microsatellite instability in gastric cancer cases was 4 of 25 patients (16%) and 4 of 26 cancers (15%). A significantly high incidence of microsatellite instability was observed in both the elderly (P < 0.01) and in lymph node metastasis-negative patients (P < 0.05). All patients with gastric cancer showing microsatellite instability were negative for lymphatic or venous permeation. A statistically significant association of microsatellite instability with no lymphatic permeation was thus observed (P < 0.05). CONCLUSIONS: This study revealed infrequent lymph node metastasis and lymph vessel invasion in the patients with gastric cancer demonstrating microsatellite instability. Although the number of examined cases was small, these findings suggest that gastric cancer that shows microsatellite instability may thus behave in a less malignant manner.

Chromosome Banding↗
PubMed1995

Overexpression of matrix metalloproteinase-7 mRNA in human colon carcinomas.

BACKGROUND: Matrix metalloproteinase-7 (MMP-7) is a member of the family of matrix-degrading metalloproteinases (MMPs) that are considered to contribute to cancer invasion and metastasis. One of the gene products that the authors have isolated by a cDNA subtraction of human gastric cancer minus normal gastric mucosa is MMP-7. The purpose of this study was to examine the expression of MMP-7 mRNA in different stages of human colorectal carcinomas. METHODS: A subtracted complementary DNA library was generated from a paired sample of human gastric carcinoma minus normal gastric mucosa. Screening of the library clones determined that MMP-7 mRNA was overexpressed. The complementary DNA insert was then used as a probe to evaluate the expression in a larger number of surgical samples of human colorectal carcinomas by Northern hybridization. RESULTS: The mRNA signal was greater in the colorectal carcinoma than in paired adjacent normal colonic or rectal mucosa in 39 of 47 cases. The expression of MMP-7 mRNA in tumor tissues increased with increasing Dukes' stage (P < 0.05). The MMP-7 mRNA expression was greatest in the metastatic liver lesions. CONCLUSIONS: The findings imply that MMP-7 mRNA is overexpressed in human colorectal carcinomas and that MMP-7 may prove useful as a marker of biologic aggressiveness.

Adenocarcinoma↗
PubMed1995

Lymphokine-activated killer cell function of lymphocytes from regional lymph nodes in patients with gastric carcinoma.

Lymphokine-activated killer (LAK) cells generated by culture of regional lymph node cells (LNC) with interleukin 2 (IL 2) for 4 and 11 days were examined for their functional capabilities in comparison with those of peripheral blood mononuclear cells (PBM) in 25 patients with gastric carcinoma. The cytotoxic activity of LAK cells induced from LNC for 4-day culture with IL 2 was significantly lower than that from PBM. However, the LNC-LAK cytotoxicity was markedly increased up to almost the same level as that of PBM after 11-day culture. The production of interferon-gamma (INF-gamma) and tumor necrosis factor-alpha (TNF-alpha) from nonadherent LAK cells in LNC was also significantly reduced as compared to that from PBM 4 days after culture, when stimulated with or without tumor target, Raji cells. After 11-day culture with IL 2, however, the levels of these cytokines produced by LNC-LAK cells either with or without stimulation by tumor target were comparable to those by PBM-LAK cells, although the release of these cytokines was markedly reduced when compared to that after 4-day culture. Phenotypic analysis revealed decreased proportion of cells mediating NK activity in LNC before and 4 days after culture. CD56+ and CD57+ cells in LNC were increased after 11-day culture, although the percentages of these cells were still low as compared to those in PBM. The proportions of OKIa1+ and CD25+ cells were uniformly increased after 4 and 11-day culture in both cell populations. Changes in subpopulations of CD4+ and CD8+ cells in LNC were not apparently different from PBM. These results indicated the differential LAK cell function of cells from regional lymph nodes from PBM in patients with gastric carcinoma.

Adult↗
PubMed1995

The expression of tumor-rejection antigen "MAGE" genes in human gastric carcinoma.

BACKGROUND & AIMS: The genes MAGE-1 and MAGE-3 both encode melanoma peptide antigens recognized by major histocompatibility complex-restricted cytotoxic T lymphocytes. The antigens may be a target for immunotherapy. There is, however, little information on the expression of these genes in gastric carcinomas. Therefore, the expression of MAGE genes in gastric carcinomas was evaluated. METHODS: The expression of MAGE-1, MAGE-2, and MAGE-3 genes in tumors and corresponding normal tissue specimens was studied using a reverse-transcription polymerase chain reaction. The results were analyzed according to clinicopathologic factors of the tumor. RESULTS: In the 68 gastric carcinomas studied, MAGE-1, MAGE-2, and MAGE-3 messenger RNA were detected in 41%, 31%, and 38%, respectively. Fifty percent of the gastric carcinomas expressed at least one of the MAGE genes. Messenger RNA for the three MAGE proteins was not detected in normal gastric tissue. MAGE gene expression in gastric carcinomas was not associated with a significant clincopathology of the tumor. However, gene expression was lower in mucinous carcinomas (3 of 10). CONCLUSIONS: MAGE-1, MAGE-2, and MAGE-3 are expressed in a high percentage of gastric carcinomas. These tumor rejection antigens may provide tumor-specific targets for immunotherapy.

Aged↗
PubMed1995

Surgical treatments for oesophageal cancer concomitant with gastric adenoma with severe epithelial atypia.

The various surgical treatments for oesophageal cancer concomitant with gastric adenoma with severe epithelial atypia (SEA) are discussed by presenting three such cases. As gastric adenoma with SEA had been considered to be a precancerous condition but not normally an indication for gastrectomy, we devised an operative strategy of laparotomy and thoracotomy. For Case 1, with early oesophageal cancer and gastric adenoma with SEA in the body of stomach, a laparotomy and local resection of the gastric lesion were carried out prior to thoracotomy in order to determine the safest reconstructive method after measuring the length of the well-nourished gastric tube. In Case 2, with advanced oesophageal cancer, a thoracotomy was first performed to assess the curability of surgery for the oesophageal cancer and a gastric adenoma was removed. In contrast, for Case 3 with advanced oesophageal cancer, and in whom post-operative survival was deemed to be short, a gastric adenoma was not resected. The most appropriate operative methods should thus be decided after careful consideration of the stage of the oesophageal cancer and characteristics of the gastric adenoma.

Adenoma↗
PubMed1995

Immunohistochemical features of HLA-DR antigen expression and lymphoid infiltrates in gastric carcinoma after low-dose interleukin-2 and mitomycin C.

We immunohistochemically evaluated lymphoid cell infiltration and HLA-DR antigen expression in gastric tumor tissue obtained from advanced gastric cancer patients 1 day after the completion of the treatment with mitomycin C (MMC) 12 mg/m2 i.v. on day 1 and recombinant interleukin-2 (IL-2) i.v. every 12 h from day 4 through day 8. Then the results were compared with those in 11 patients pretreated with MMC alone, 5 treated with IL-2 alone, and 24 untreated patients. Widespread lymphoid infiltration was observed in 17% of untreated tumors, 27% of MMC-pretreated tumors, and 40% of tumors treated with IL-2 alone. However, 71% of carcinomas pretreated with MMC plus IL-2 exhibited widespread infiltration. The frequency of cases with high-grade infiltration of CD4+ cells was significantly higher in either group of patients treated with MMC alone or MMC plus IL-2. Because the CD8+ cell infiltration was not significantly altered, the ratio of CD4+ to CD8+ cells estimated as being > 1 was more frequently noted in patients given MMC alone or MMC plus IL-2, as compared with untreated control. Furthermore, 86% of tumors pretreated with MMC plus IL-2 exhibited positive HLA-DR antigen expression, whereas 29% of untreated carcinomas did so. MMC or IL-2 alone did not significantly increase HLA-DR expression. These results indicate that the combination of low-dose of IL-2 with MMC enhances the intensity of lymphoid cell infiltration in tumors, with the predominance of CD4+ cells, and HLA-DR antigen expression on tumor cells in patients with advanced gastric carcinoma.

Aged↗
PubMed1995

The heterogeneity of microsatellite instability in multiple gastric cancers.

To obtain a better understanding of the role of genetic instability in developing gastric cancer, it is of great interest to examine microsatellite alterations in synchronous multiple gastric cancers that are thought may have the same genetic background and the same microenvironment of the stomach. We report our experience with two patients with synchronous multiple gastric cancers; patient 1 showed two carcinomas in the stomach, whereas patient 2 showed two carcinomas and two adenomas in the stomach. We examined the DNAs from the two cases for microsatellite instability and expected that the status of microsatellite instability in each tumor from the same stomach would be the same. However, patient 2 revealed heterogeneity in the microsatellite instability, i.e., an early cancer that showed some apparent alterations, whereas the other advanced cancer and two adenomas did not. On the other hand, neither of the two carcinomas in patient 1 showed microsatellite instability. To our knowledge, there has been no previous report of microsatellite instability in multiple gastric cancers. In this report, we describe a case that revealed such a heterogeneity of the microsatellite instability, in which the carcinogenic process of each tumor may undergo different genetic alterations even under the same genetic conditions and background.

Aged↗
PubMed1994

Molecular genotyping for N-acetylation polymorphism in Japanese patients with colorectal cancer.

BACKGROUND: N-acetylation polymorphism has been documented as a representative pharmacogenetic trait, and also has been implicated ecogenetically in an individual's susceptibility to cancer. However, there still remains controversy concerning the association between colorectal cancer and N-acetylation polymorphism. METHODS: A newly established molecular genotyping method using polymerase chain reaction-based restriction fragment length polymorphism to analyze the distribution of polymorphism in a large group of Japanese patients with colorectal cancer was used. RESULTS: Based on an analysis of 234 Japanese patient with colorectal cancer and 329 healthy control subjects, no significant difference was observed in either the distribution of acetylator phenotypes or of allele frequencies between the two groups. In addition, no significant difference in their distribution was found based on the age at which cancer was first detected, the location of tumors, or the histopathologic features. CONCLUSIONS: N-acetylation polymorphism does not appear to be implicated crucially as a genetic trait affecting an individual's susceptibility to colorectal cancer.

Acetylation↗
PubMed1994

Lymphokine-activated killer cell activity of peripheral blood, spleen, regional lymph node, and tumor infiltrating lymphocytes in gastric cancer patients.

Lymphokine-activated killer (LAK) cell activity of peripheral blood mononuclear cells (PBM), spleen cells (SPC), regional lymph node cells (LNC), and tumor-infiltrating lymphocytes (TIL), induced by activation with interleukin 2 (IL 2) for 4 days, was evaluated in patients with gastric carcinoma. TIL exhibited the lowest LAK activity and the cytotoxicity of LNC was significantly lower than that of either PBM or SPC. There was no difference between PBM and SPC. Then, there were significant correlations of LAK activity among PBM, SPC, and LNC, whereas poor correlations were observed in the cytotoxicity between TIL and PBM, SPC, or LNC. Phenotypic analysis of each cell population was performed before and after activation with IL 2. Before culture, the cells mediating natural killer (NK) activity such as CD16+, CD56+, and CD57+ cells were few in LNC and TIL. However, CD56+ and CD57+ cells in TIL were increased after culture. Then, CD4+Leu8+ and CD8+CD11+ cells, which identify suppressor cell function, were not elevated in LNC or TIL, as compared to that in PBM or SPC. Further, the proportions of OKIa1+ and CD25+ cells expressing T-cell activation and IL 2 receptor were uniformly increased in all cell populations after culture. These results indicate the differential reactivity of each lymphocyte population to IL 2 and fundamental dysfunction of LNC and, especially TIL, suggesting the specific influence of the local tumor environment on the lymphocyte function in the area in patients with gastric carcinoma.

Adult↗
PubMed1994

Neuroleptic malignant syndrome occurring after an emergency operation for traumatic duodenal perforation: report of a case.

Neuroleptic malignant syndrome (NMS) is a potentially fatal complication which may develop in psychiatric patients taking neuroleptic drugs. We report herein the successful treatment of a 33-year-old schizophrenic man, prescribed neuroleptic drugs, who underwent an emergency operation for traumatic duodenal perforation with a retroperitoneal infection. Five days after the operation, he began to demonstrate clinical features consistent with NMS such as high fever, abnormalities in vital signs, leukocytosis, and an elevated serum level of creatine phosphokinase; however, these findings were first presumed to be secondary to either the preexisting tissue injuries or to postoperative complications. A definite diagnosis of NMS was thus delayed until muscle rigidity and autonomic instability became evident. After a tentative diagnosis of NMS had been made, sodium dantrolene, a drug used specifically for the treatment of NMS, was administered and the patient's condition remarkably improved. Since NMS can be induced by either interrupting the course of neuroleptic drugs or by the additional administration of sedative drugs, and since its mortality rate is high if prompt and appropriate treatment is not carried out, surgeons should bear in mind the possibility of NMS developing postoperatively in psychiatric patients.

Adult↗
PubMed1994

Enhanced induction of lymphokine-activated killer activity following a single dose of cisplatin in cancer patients.

The effects of intravenous cisplatin (CDDP) administration on the generation of lymphokine-activated killer (LAK) activity in peripheral blood mononuclear (PBM) cells were investigated in cancer patients. The ability of PBM to generate LAK activity was significantly augmented 3, 5 and 7 days after a single dose, 50 mg m-2, of CDDP injection when compared to that before injection. NK activity of PBM was not altered. The distribution of lymphocyte subsets exhibited no significant change following CDDP injection, except CD2+ cells. However, the ability of monocytes in PBM to produce TNF-alpha was significantly enhanced 5 days after the drug administration, although IL-1-alpha and IL-1-beta production was not augmented.

Cisplatin↗
PubMed1994

Minimal increase in serum interleukin-6 levels during laparoscopic cholecystectomy.

The chronologic changes in the serum levels of interleukin-6 (IL-6), a mediator for acute-phase inflammation, were compared between laparoscopic cholecystectomy (LC) and open cholecystectomy (OC), since these two types of operations were considered to be a unique model for examining the role of local tissue injury in postoperative inflammatory reactions. The increase in the serum IL-6 level during LC was found to be significantly smaller than that during OC and resulted in a smaller extent of postoperative elevations for C-reactive protein. These results suggest that laparoscopic surgery associated with minimal tissue injury can help limit an increase in the serum IL-6 level during surgery, thus contributing to a reduction in surgical stress.

Biomarkers↗
PubMed1994

Interrelationship between estradiol and tamoxifen responses for clinical breast carcinoma cells cultured on contact-sensitive plates.

An in vitro assay system for predicting the estradiol (E2) sensitivity of clinical cancer cells was applied to 54 patients with breast carcinoma to compare the responses to E2 and tamoxifen (TAM) with the estrogen receptor (ER) status. We found that 18 of the 35 cases in the ER-positive group and 6 of the 19 cases in the ER-negative group were stimulated by E2. It is suggested that ER status alone can not predict the response of cultured cells to E2 in clinical breast cancer. Cell growth of 11/35 (31%) of the ER-positive cases and that of 8/19 (42%) of the ER-negative cases was inhibited by E2. Since the cases inhibited by E2 could not be distinguished by ER status alone, an assay system based on a quantitative proliferative response was considered necessary. There were 20 (83%) cases of inhibition by TAM among the 24 stimulated by E2. Only 18/35 (51%) of the ER-positive group exhibited growth inhibition by TAM. In our (CSP) assay, 20 (83%) of the 24 cases stimulated by E2 were inhibited by TAM, 10 (91%) of the 11 E2-insensitive cases were insensitive to TAM and 13 (68%) of the 19 cases inhibited by E2 were stimulated by TAM. In short, TAM response and E2 response tended to be inversely related (43/54 = 80%, P < 0.01). Furthermore, the E2-response rate showed a good correlation with the TAM-response rate (R2 = 0.825). These results indicate the feasibility of predicting individual tumor responses to either E2 or TAM by using CSPs.

3T3 Cells↗