Biomedical subjects

H Ueo

Publications and source records attributed to H Ueo.

At least 19 recordsLinked to original sources

PubMed2001

Clinical significance of K-Ras mutations in intraoperative tumor drainage blood from patients with colorectal carcinoma.

BACKGROUND: Recurrent and metastatic carcinoma of the colorectum remains a major problem. This may be ascribed to the presence of micrometastasis at diagnosis. The purpose of this study was to analyze prospectively the clinical value of detecting K-ras mutations in the perioperative circulating blood from patients with colorectal carcinoma. METHODS: Twenty-four patients whose tumor carried mutations in codon 12 of the K-ras gene were studied for the presence of cancer cells in perioperative blood samples, in particular, tumor drainage samples. A detection assay using CD45 immunomagnetic separation plus nested mutant allele specific amplification (MASA) was performed. RESULTS: K-ras mutations in CD45 negative cells in tumor drainage blood were detected in 7 (29.2%) of 24 patients. There was no significant relationship between the presence of a K-ras mutation and clinicopathological features. Four (57.1%) of the seven patients with a positive K-ras mutation in drainage blood had early recurrent disease. Of the 17 patients with no K-ras mutation, none developed metastatic disease. The recurrence rate of the K-ras mutation positive group was higher than that of the K-ras mutation negative group (P < .01). There was a significant difference, regarding prognosis, between K-ras mutation positive and negative groups (P < .01). CONCLUSIONS: This preliminary study demonstrates that the detection of circulating cancer cells in the tumor drainage blood by our new assay system may provide a predictor of recurrence and metastasis of colorectal cancer.

Adenocarcinoma↗

PubMed2001

A novel isoform of human fibroblast growth factor 8 is induced by androgens and associated with progression of esophageal carcinoma.

Human esophageal carcinomas occur more frequently in males, suggesting that androgens may play a role in the regulation of gene expression associated with malignant transformation. We previously established an androgen-sensitive squamous cell carcinoma line, KSE-1, from a male patient with esophageal cancer; recently a novel isoform of human fibroblast growth factor 8 (FGF8f, isoform FGF8b) was identified and expressed following androgen stimulation of KSE-1 cells. The predicted amino acid sequence of FGF8f contained an additional 29 amino acids when compared to FGF8b. Flutamide, an androgen antagonist, inhibited both FGF8b and FGF8f transcription in a dose-dependent manner. Tissue analysis from tumors revealed FGF8b expression in 24 of 41 male, but in 0 of 9 female esophageal carcinomas (58.5%), and none in adjacent normal esophageal mucosa. In addition, FGF8f was detected in 9 of 24 FGF8b-positive tumors (37.5%), and this observation was significantly associated with a poor prognosis (P < 0.001). Our observations suggest that androgenic exposure will induce FGF isoforms in tumor cells, and expression of these growth factors is associated with the prevalence and prognosis of esophageal carcinoma in males.

Androgen Antagonists↗

PubMed2001

Genetic polymorphism of N-acetyltransferase 2 in patients with esophageal cancer.

OBJECTIVE: N-Acetylation polymorphism is a representative genetic trait related to an individual's susceptibility to several cancers. However, there remains a controversy and no consensus concerning whether there is a true association between esophageal cancer and N-acetylation polymorphism. METHODS: To analyze the distribution of N-acetyltransferase 2 polymorphism in Japanese patients with esophageal squamous cell cancer, a molecular genotyping method using a polymerase chain reaction-based restriction fragment length polymorphism was used. RESULTS: Based on an analysis of 71 Japanese patients with esophageal squamous cell cancer and 329 healthy control subjects, the distribution of the slow acetylator phenotype was significantly higher in esophageal cancer patients than in the controls (19.7% and 9.4%, respectively, p = 0.040). The odds ratio of esophageal cancer for the slow phenotype was 2.55 (95% CI = 1.15-5.65, p = 0.023) compared with the rapid type. Furthermore, a significant difference between the distribution of acetylator phenotype and the incidence of lymph node metastasis and lymphatic involvement was found based on the clinicopathological features of these cancers. Esophageal cancer patients with a higher smoking exposure history tended to have the rapid acetylator phenotype. CONCLUSION: These results suggest that N-acetylation polymorphism may be implicated as a genetic trait affecting an individual's susceptibility and biological behavior of esophageal squamous cell cancer.

Aged↗

PubMed2001

Overexpression of HRad17 mRNA in human breast cancer: correlation with lymph node metastasis.

PURPOSE: A novel human gene, designated HRad17, was identified as the human homologue of the Rad17 of Schizosaccharomyces pombe and Rad24 of Saccharomyces cerevisiae. In yeast, these genes play a critical role in maintaining genomic stability. The aim of this study was to evaluate the expression of HRad17 in human breast cancer. EXPERIMENTAL DESIGN: We investigated HRad17 mRNA expression in 64 cases of human breast cancer by means of reverse-transcription-PCR, in situ hybridization, and immunohistochemistry. RESULTS: The HRad17 mRNA was overexpressed in 35 cases (54.7%). Twenty-four (68.6%) of 35 cases with HRad17 overexpression in cancer tissues were node-positive, whereas only 8 (27.6%) of 29 cases without HRad17 overexpressions were node-positive. The expression of HRad17 mRNA correlated with both lymph node metastasis (P = 0.001) and high Ki67 labeling index (P = 0.006). Although not significantly different, expression of HRad17 mRNA tended to correlate with tumor size (P = 0.06) and expression of mutant p53 protein (P = 0.10). Furthermore, expression of HRad17 mRNA was an independent predictor of axillary lymph node metastasis as well as of lymphatic permeation by multivariate analysis (P < 0.0001). CONCLUSIONS: Our study demonstrates that HRad17 might be related to the development of lymph node metastasis in human breast cancers. Although its function still remains unclear, the expression of HRad17 mRNA could open up a new window for the diagnostic staging and treatment of human breast cancers.

Adult↗

PubMed2000

Prognostic impact of tissue inhibitor of matrix metalloproteinase-1 in esophageal carcinoma.

Tissue inhibitor of metalloproteinase-1 (TIMP-1) inhibits the activity of matrix metalloproteinase, which may play an important role in carcinoma invasion and metastasis. TIMP-1 is thus considered to inhibit carcinoma invasion and metastasis. However, TIMP-1 possesses another important function, cell growth promotion. The clinical significance of TIMP-1 expression has not been fully determined in esophageal carcinoma. We thus examined the expression of TIMP-1 mRNA in tumor (T) and corresponding normal (N) tissues of 85 esophageal carcinoma cases by RT-PCR. The T:N ratio of TIMP-1 mRNA expression in each case was evaluated semi-quantitatively with adjustment by an internal control gene. The mean T:N ratio was 2.0 (range 0.2-6.5). When comparing high-expression cases (T:N > 2.0, n = 37) with low-expression cases (T:N < or = 2.0, n = 48), the former showed a significantly higher frequency of lymph vessel invasion, vascular vessel invasion, lymph node metastasis and advanced-stage disease. The former cases showed a poorer prognosis than the latter. Multivariate analysis disclosed that TIMP-1 expression status was an independent determining factor for prognosis. Our findings suggest that TIMP-1 expression correlates with tumor extension of esophageal carcinoma and might, if validated, prove useful as a novel prognostic marker for esophageal carcinoma.

Aged↗

PubMed2000

Second cancers after adjuvant tamoxifen therapy for breast cancer in Japan.

BACKGROUND: Women treated with tamoxifen for breast cancer are at increased risk of endometrial cancer. We conducted a retrospective cohort study to evaluate the risk of second primary cancers after adjuvant tamoxifen therapy for breast cancer in Japan. PATIENTS AND METHODS: The subjects of the study were 6148 women who had been diagnosed with stage I, II, or IIIA unilateral primary breast cancer and had received surgical treatment during the period from January 1982 through December 1990 at nine institutions in Japan. The information on each patient was obtained from medical records or a prospectively compiled computer database at each institution. RESULTS: Of the 6148 women, 3588 (58.4%) were administered tamoxifen as an adjuvant treatment and 2560 (41.6%) were not administered. Median follow-up periods were 7.64 years for tamoxifen-treated patients and 8.10 years for non-tamoxifen-treated patients, respectively. The duration of tamoxifen treatment was mostly two years or less (80.7%), and few patients received tamoxifen for more than five years. The cumulative incidence rates of all second cancers at 10 years were 4.61% and 4.09% among tamoxifen-treated and non-tamoxifen-treated patients (P = 0.62), respectively, and the incidence rate ratio (IRR) for all second cancers was 1.06 (95% confidence interval (CI): 0.77-1.47) after adjustment of several covariates. The numbers of endometrial cancers was 9 and 3 among tamoxifen-treated and non-tamoxifen-treated patients, respectively, and the IRR was 2.37 (95% CI: 0.64-8.77, P = 0.20). Of the 12 patients who developed endometrial cancer, 4 died of cancer (for 3 of them, the cause of death was breast cancer), and the other 8 patients were alive as of March 1996. Stomach cancer was the most frequent second cancer and the IRR was 1.34 (95% CI: 0.76-2.38, P = 0.31). There was no substantial increase in any other type of gastrointestinal cancer such as colorectal and liver cancers among tamoxifen-treated patients. CONCLUSIONS: The incidence and risk of second primary cancers associated with tamoxifen therapy is low. The potential benefit of adjuvant tamoxifen therapy in breast cancer patients outweighs the risk of second primary cancers for Japanese breast cancer patients.

Adult↗

PubMed2000

L-myc restriction fragment length polymorphism in Japanese patients with esophageal cancer.

L-myc polymorphism is a representative genetic trait related to an individual's susceptibility to several cancers. However, there have been no reports concerning the association between esophageal cancer and L-myc polymorphism. To analyze the distribution of polymorphism in Japanese patients with esophageal cancer, a molecular genotyping method using a polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) was used. Based on an analysis of 65 Japanese patients with esophageal cancer and 107 healthy control subjects, a significant difference was observed in either the distribution of genotypes (P=0.012) or of allele frequencies between the two groups (P=0.004). The relative risk of esophageal cancer for genotypes including the shorter allele was 2.9 compared to the longer allele homozygote. Furthermore, the patients with S-allele had a tendency for poor prognosis among those with three genotypes. A significant difference between the distribution of genotypes and the incidence of lymph node metastasis was found based on the clinicopathological features of the cancers. These results suggest that L-myc polymorphism may be implicated as a genetic trait affecting an individual's susceptibility to esophageal cancer, at least among Japanese patients.

Esophageal Neoplasms↗

PubMed2000

RT-PCR detection of breast cancer cells in sentinel lymph modes.

Sentinel lymph node (SLN) biopsy is being evaluated in breast cancer patients to improve detection of metastases and to guide therapy with minimal morbidity. The aim of this study was to increase the sensitivity of tumor cell detection in SLNs using superior reverse transcription polymerase chain reaction (RT-PCR) for carcinoembryonic antigen (CEA) and mammaglobin (MMG) analysis rather than current methods which fail to identify clinically relevant disease in many patients. In seventy stage I and II breast cancer patients dye-guided lymph node mapping was performed and the SLNs were divided alternately for RT-PCR or hematoxylin and eosin staining (H&E). RT-PCR and H&E diagnosis of SLNs were compared. SLNs were identified in 66/70 (94.3%) patients. Seventeen patients (26. 2%) had histological metastasis in SLNs. CEA was expressed in 25.0% of 48 patients with H&E negative SLNs, and MMG was expressed in 20. 8%. SLNs could predict axillary lymph node status with 95.4% accuracy and 6.3% false negative rate by H&E. Moreover, RT-PCR improved these to 98.5% and 2.8%, respectively. SLN diagnosis using RT-PCR is a powerful and sensitive method, which increases the accuracy of clinical staging and may provide more informed choices for appropriate therapeutic management of breast cancer patients.

Adult↗

PubMed1999

Generation of specific antitumor reactivity by the stimulation of spleen cells from gastric cancer patients with MAGE-3 synthetic peptide.

The induction of cytotoxic T lymphocytes (CTL) from peripheral blood mononuclear cells (PBMC) using MAGE peptide has been investigated in order to use MAGE antigens immunotherapeutically. We therefore developed a simplified method for inducing peptide-specific CTL that kill tumor cells expressing MAGE from the PBMC of either healthy donors or even cancer patients. Since the spleen is a major lymphoid organ, we used a simple method to examine the capacity of spleen cells to generate MAGE-specific CTL by in vitro stimulation with MAGE peptide in gastric cancer patients. The CTL responses could thus be induced from unseparated spleen cells in HLA-A2 patients with gastric carcinoma expressing MAGE-3 by stimulating these cells with autologous spleen cells pulsed with HLA-A2-restricted MAGE-3 peptide as antigen-presenting cells and by using keyhole limpet hemocyanin and interleukin-7 for the primary culture. The induced CTL were thus able to lyse HLA-A2-positive carcinoma cells transfected with MAGE-3 and expressing MAGE-3, as well as the target cells pulsed with the peptide, in an HLA-class-I or -A2-restricted manner. Since MAGE-specific CTL could be induced from the spleen cells of gastric cancer patients, the spleen appears to play an important role in either clinical tumor vaccination or the treatment of cancer patients by adoptive immunotherapeutic approaches using the MAGE peptide.

Antibodies, Monoclonal↗

PubMed1999

Up-regulated pyrimidine nucleoside phosphorylase in breast carcinoma correlates with lymph node metastasis.

BACKGROUND: The clinical significance of pyrimidine nucleoside phosphorylase (PyNPase) activity in breast carcinomas has never been determined. MATERIALS AND METHODS: In 41 cases of breast carcinoma, the enzyme activity of PyNPase was determined by the high performance liquid chromatography (HPLC) assay and its value was analyzed with clinicopathologic variables. The expression level of mRNA was examined by the semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) assay and compared with the enzyme activity. RESULTS: The higher activity of PyNPase was significantly correlated not only with the presence of vascular permeation (P = 0.02) but of lymph node metastasis (P = 0.02). The mRNA expression correlated well with the enzyme activity (r = 0.74, P < 0.01). A multivariate analysis disclosed the PyNPase factor to be associated with lymph node metastasis. In addition, 17 (41%) showed positive staining only in the tumor stromal cells and 18 (44%) cases showed positive staining in both the tumor stromal cells and the carcinoma cells by immunohistochemical study. CONCLUSIONS: These findings suggest that PyNPase activity is a new marker predicting the malignant potential of breast carcinomas, especially with respect to lymph node metastasis, and that the RT-PCR assay is a more useful method than direct evaluation of PyNPase activity.

Adenocarcinoma↗

PubMed1999

Lack of DMBT1 expression in oesophageal, gastric and colon cancers.

Loss of sequences from human chromosome 10q has been reported in several different cancers. Recently, a second candidate tumour-suppressor gene, DMBT1, was identified in this chromosomal region. We studied the mRNA expression and homozygous deletion of this gene in human oesophageal, gastric and colon cancers. Reverse transcriptase polymerase chain reaction (RT-PCR) amplification demonstrated that 23 (53.5%) of 43 oesophageal, 5 (12.5%) of 40 gastric, and 4 (16.7%) of 24 colorectal cancer cases showed an apparent reduction in DMBT1 mRNA in tumour tissues compared with paired normal tissues. Twelve out of 15 oesophageal cancer cell lines also showed no expression. We next studied homozygous deletions within the DMBT1 gene in oesophageal cancers by using duplex PCR. Consequently, it was recognized in five (11.6%) of the primary tumours and two (13.3%) of the cell lines. These findings suggest that DMBT1 may act as a tumour-suppressor gene not only in brain tumours but also in gastrointestinal cancers, especially in oesophageal cancers.

Agglutinins↗

PubMed1999

Expression of pyrimidine nucleoside phosphorylase mRNA plays an important role in the prognosis of patients with oesophageal cancer.

To clarify the significance of the expression of pyrimidine nucleoside phosphorylase (PyNPase) mRNA as a predictive factor for the prognosis of patients with oesophageal carcinoma, the PyNPase mRNA in the tumours and normal tissues from 55 resected cases of oesophageal carcinoma was examined by a reverse transcription polymerase chain reaction (RT-PCR). As a result, a positive correlation was observed between the tumour/normal (T/N) ratio of the expression of PyNPase mRNA by RT-PCR and that of the enzyme activity of PyNPase based on the findings of an enzyme linked immunosolvent assay (r = 0.594, P = 0.009). The T/N ratio of the expression of PyNPase mRNA was significantly higher in the cases with lymph vessel invasion (P = 0.013), lymph node metastasis (P = 0.0016), and an advanced stage of the disease (P = 0.021) than those without these factors. The patients with a higher T/N ratio of PyNPase mRNA showed significantly worse prognosis than those with a lower T/N ratio (P = 0.023 with log-rank tests). A multivariate analysis for the cumulative survival rates revealed that a high T/N ratio of the expression of PyNPase mRNA was independently related to a poor prognosis. These findings suggested that the determination of PyNPase mRNA by RT-PCR thus appears to be a new useful parameter for identifying both a poor prognosis and a highly malignant potential of oesophageal carcinoma.

Adult↗

PubMed1998

Association between restriction fragment length polymorphism of the L-myc gene and susceptibility to gastric cancer.

BACKGROUND: L-myc polymorphism has been documented to be a representative genetic trait which is related an individual's susceptibility to several cancers. However, there have been no reports concerning any significant association between susceptibility to gastric cancer and L-myc polymorphism. METHODS: The distribution of L-myc polymorphism in 61 patients with gastric cancer was determined by polymerase chain reaction-based restriction fragment length polymorphism and compared with that of 107 healthy control subjects. RESULTS: There was a significant difference in the distribution of both genotypes (P = 0.024) and allele frequencies (P = 0.026) between the two groups. The relative risk of gastric cancer for genotypes with the shorter (S) allele was 3.09 compared with the longer (L) allele homozygote. No significant correlation with clinicopathological features of the cancers except for prognosis was found. The patients with SS genotypes had a worse prognosis than those with LL or LS genotypes (P = 0.029). CONCLUSION: L-myc polymorphism may be significant in an individual's susceptibility to gastric cancer in Japan, and may be a useful marker for identifying patients at high risk of developing gastric cancer.

Disease Susceptibility↗

PubMed1998

Clinical significance of molecular detection of carcinoma cells in lymph nodes and peripheral blood by reverse transcription-polymerase chain reaction in patients with gastrointestinal or breast carcinomas.

PURPOSE: This study evaluates the clinical significance of detection of carcinoembryonic antigen (CEA) mRNA in the dissected lymph nodes and peripheral blood samples of patients with gastrointestinal or breast carcinomas. PATIENTS AND METHODS: A total of 406 lymph nodes obtained from 65 patients were analyzed by both histologic and molecular examination of CEA-specific reverse transcriptase-polymerase chain reaction (RT-PCR). Peripheral blood samples from another 102 patients were also analyzed by CEA-specific RT-PCR. Patients were followed up prospectively for 24 +/- 12 months. RESULTS: Of 406 lymph nodes, the positive detection rate increased from 20% by histologic examination to 60% by RT-PCR examination. The recurrence rate was 40% in 15 cases showing positive results in both examinations, 14% in 29 cases showing histologically negative but RT-PCR positive results, and none in 21 cases showing negative results in both examinations. The positive detection rate for CEA mRNA in peripheral blood samples increased with advancing stage of disease. With respect to 62 curatively operated cases, CEA mRNA was detected in 12 cases. Four of these 12 cases developed metastatic disease after surgery whereas none of 50 cases negative by RT-PCR developed metastasis. CONCLUSION: It has been shown that RT-PCR is a powerful tool to detect CEA mRNA in the lymph nodes or the peripheral blood. This is potentially very useful to determine high-risk patients for metastasis. Serial analysis is warranted to assess the long-term significance of this method and its therapeutic and prognostic implications.

Breast Neoplasms↗

PubMed1998

Expression of ornithine decarboxylase mRNA and c-myc mRNA in breast tumours.

We examined the expression of ornithine decarboxylase (ODC) mRNA in 53 female cases of breast cancer by a reverse transcriptase-polymerase chain reaction (RT-PCR) assay to determine the clinicopathologic significance of its expression. A significantly higher expression of ODC mRNA was, observed in younger patients than in older patients. The patients with a larger sized tumour possessed a significantly higher expression of ODC mRNA. In addition, the cases with a poor prognosis showed significantly higher expression of ODC. Previous studies have reported in vivo and in vitro correlation between the expression of ODC and c-myc genes in human carcinomas. We disclosed a significant correlation between these genes in primary breast carcinomas. We conclude that the expression of ODC may potentially be a new biological marker for breast carcinoma.

Adolescent↗

PubMed1998

Expression of insulin-like growth factor 2 mRNA in human gastric cancer.

Insulin-like growth factor 2 (IGF2) stimulates cell proliferation and development in normal human growth. In several human cancers, the IGF2 gene is overexpressed and is thus considered to be a growth factor for tumors mediated through both the paracrine and autocrine pathways. However, the significance of IGF2 mRNA expression in gastric cancer has yet to be clarified. We semi-quantitatively measured the expression of IGF2 mRNA in 57 Japanese cases of gastric cancer by means of the reverse transcription polymerase chain reaction and also analyzed the relation between the IGF2 expression status and other clinicopathologic factors. We also performed immunohistochemical staining for IGF2. In 41 of 57 cases (72%), the expression of IGF2 mRNA was greater in tumor tissue (T) than in normal tissue (N). The average tumor/normal (T/N) expression ratio of IGF2 mRNA corrected for that of control gene mRNA was 1.42, while ranging from 0.36 to 3.65. The T/N ratio of infiltrative-type cancers was greater than that of expanding-type cancers (p<0.05). The cases with lymphatic permeation showed a greater T/N ratio than those without lymphatic permeation in expanding-type cancers (p<0. 05). Immunohistochemical staining revealed IGF2 to be detected in cancer cells themselves, especially at the margin of the cancer tissue. The IGF2 gene may thus play an important role in lymph vessel permeation especially in expanding-type gastric cancers.

Gene Expression↗

PubMed1998

Expression spectrum of melanoma antigen-encoding gene family members in colorectal carcinoma.

OBJECTIVE: The 12 members of the human melanoma antigen-encoding (MAGE) gene family encode tumor-specific peptide antigens. Some antigens coded by the MAGE genes are potentially useful for cancer-specific immunotherapy. However, little information on the expression of these genes in human colon carcinomas is available. We investigated the expression of 10 of the 12 genes in human colon tissue. DESIGN: Eighty pairs of tumor and normal tissue samples from the human colon were studied by means of reverse transcription-polymerase chain reaction. RESULTS: None of the genes was expressed in the 80 control samples of normal tissue. On the other hand, expression was recognized in tumor samples, ranging from 5% of samples for MAGE-6 to 44% for MAGE-8. Seventy of the 80 tumor samples (88%) expressed at least 1 of the 10 MAGE genes. The frequency of liver metastasis was significantly higher in cases with tumor samples that expressed MAGE-3 than in those that did not express this gene. This tendency was not observed for other members of the MAGE gene family. No significant differences were observed in the other clinicopathologic factors between any MAGE-positive and -negative tumor cases. CONCLUSIONS: The MAGE genes were exclusively expressed in carcinoma tissues and not in normal tissues of the colon. The finding that nearly 90% of tumors expressed at least one MAGE gene indicates the possible clinical use of this gene for both immunotherapy and molecular diagnosis.

Antigens, Neoplasm↗

PubMed1998

Motility related protein 1 (MRP1/CD9) expression in colon cancer.

It is important to detect genes that may be good prognostic markers for colon cancer patients. With this in mind, we identified the motility related protein-1 (MRP1/CD9) gene in human colon tissues. The aim of this study was to clarify the significance of MRP1/CD9 gene expression in human colon cancers. We performed the differential mRNA display technique between tumor/normal paired samples of the colon and identified MRP1/CD9. Eighty-two surgical specimens of primary colorectal cancer were analyzed by means of reverse transcription-PCR for the MRP1/CD9 gene. Its expression status and clinicopathological variables were analyzed univariately and multivariately. The MRP1/ CD9 mRNA expression was positive in 56 cases and negative in 26 cases. The MRP1/CD9 negative cases showed a significantly higher frequency of venous-vessel invasion and liver metastasis, or a worse prognosis than the MRP1/CD9 positive cases (P < 0.05). Multivariate analysis with the Cox regression model disclosed that MRP1/CD9 expression was an independent prognostic factor distinct from the lymph node status. The findings imply that the study of MRP1/CD9 expression may be useful for predicting prognosis of patients with colorectal cancer.

Aged↗