Biomedical subjects

Gen Tamura

Publications and source records attributed to Gen Tamura.

At least 37 records · Page 2Linked to original sources

PubMed2004

Variations in the C3, C3a receptor, and C5 genes affect susceptibility to bronchial asthma.

Bronchial asthma (BA) is a common chronic inflammatory disease characterized by hyperresponsive airways, excess mucus production, eosinophil activation, and the production of IgE. The complement system plays an immunoregulatory role at the interface of innate and acquired immunities. Recent studies have provided evidence that C3, C3a receptor, and C5 are linked to airway hyperresponsiveness. To determine whether genetic variations in the genes of the complement system affect susceptibility to BA, we screened single nucleotide polymorphisms (SNPs) in C3, C5, the C3a receptor gene (C3AR1), and the C5a receptor gene (C5R1) and performed association studies in the Japanese population. The results of this SNP case-control study suggested an association between 4896C/T in the C3 gene and atopic childhood BA (P = 0.0078) as well as adult BA (P = 0.010). When patient data were stratified according to elevated total IgE levels, 4896C/T was more closely associated with adult BA (P = 0.0016). A patient-only association study suggested that severity of childhood BA was associated with 1526G/A of the C3AR1 gene (P = 0.0057). We identified a high-risk haplotype of the C3 gene for childhood (P = 0.0021) and adult BA (P = 0.0058) and a low-risk haplotype for adult BA (P = 0.00011). We also identified a haplotype of the C5 gene that was protective against childhood BA (P = 1.4 x 10(-6)) and adult BA (P = 0.00063). These results suggest that the C3 and C5 pathways of the complement system play important roles in the pathogenesis of BA and that polymorphisms of these genes affect susceptibility to BA.

Adult↗

PubMed2004

Peritumoral CpG oligodeoxynucleotide treatment inhibits tumor growth and metastasis of B16F10 melanoma cells.

Although melanoma mostly affects the skin, it is notorious for its propensity to easily develop metastasis. Metastatic melanoma is highly resistant to a variety of therapies. We examined the anti-metastatic potential of peritumoral monotherapy against murine cutaneous B16F10 melanoma with synthetic oligodeoxynucleotides (ODN) containing unmethylated CpG motifs. We demonstrated that repeated peritumoral injections of CpG ODN significantly reduced skin tumor size. Peritumoral CpG ODN-treatment of skin tumors prevented the development of pulmonary B16F10 colonies. Adoptive transfer of splenocytes obtained from CpG ODN-treated mice markedly reduced the number of previously established pulmonary colonies in recipient naïve mice. T-lymphocyte depletion studies indicated that the anti-metastatic effect was dependent on both CD4+ and CD8+ T cells. These results suggest that CpG ODN are promising as a preventive and therapeutic anti-metastatic measure against melanoma.

Adoptive Transfer↗

PubMed2004

Promoter hypermethylation of DAP-kinase is associated with poor survival in primary biliary tract carcinoma patients.

To clarify the clinicopathological significance of promoter hypermethylation of tumor suppressor and tumor-related genes in biliary tract carcinomas, we examined the promoter methylation status of multiple genes in primary biliary tract carcinomas. These consisted of carcinomas of the bile duct, gallbladder, and duodenal ampulla. Surgical specimens were obtained from a total of 37 patients with biliary tract carcinoma. The cohort consisted of 23 patients with bile duct carcinoma, 9 patients with gallbladder carcinoma, and 5 patients with ampullary carcinoma. The methylation status of CHFR, DAP-kinase, E-cadherin, hMLH1, p16, RASSF1A, and RUNX3 was examined by methylation-specific polymerase chain reaction (MSP). The correlation between methylation status and clinicopathological characteristics was then assessed. The methylation frequencies of CHFR, DAP-kinase, E-cadherin, hMLH1, p16, RASSF1A, and RUNX3 genes were 16.2%, 21.4%, 27.0%, 8.1%, 24.3%, 27.0%, and 56.8%, respectively, in primary biliary tract carcinomas. The number of methylated genes per sample was 2.17 +/- 0.28 (average +/- SD) in bile duct carcinomas, 1.80 +/- 0.97 in ampullary carcinomas, and 0.89 +/- 0.35 in gallbladder carcinomas, with a statistically significant difference between bile duct carcinomas and gallbladder carcinomas (P = 0.02). As for clinicopathological significance, patients with a methylated RUNX3 promoter were significantly older than those with unmethylated RUNX3 (P = 0.01), and DAP-kinase methylation was more frequent in poorly differentiated tumors than in well to moderately differentiated ones (P = 0.04). The overall survival rate was significantly lower in patients with methylated DAP-kinase (P = 0.009) or RUNX3 (P = 0.034) compared to those with unmethylated genes. Furthermore, DAP-kinase methylation-positive status was independently associated with poor survival in multivariate analyses (hazard ratio = 8.71, P = 0.024). A significant proportion of primary biliary tract carcinomas exhibited promoter hypermethylation of tumor suppressor and tumor-related genes, although bile duct carcinomas are more prone to being affected by promoter methylation than are gallbladder carcinomas. Hypermethylation of DAP-kinase appears to be a significant prognostic factor in primary biliary tract carcinomas.

Age Distribution↗

PubMed2004

Long-term use of corticosteroid eye drops delays the spontaneous remission of pulmonary sarcoidosis.

Topical corticosteroid eye drops are commonly used for ocular sarcoidosis. That systemic absorption of corticosteroids by eye drops may influence the clinical course of sarcoidosis may be speculated because it has been reported that the serum concentration of corticosteroids after drop administration was dose-related. To evaluate the effects of corticosteroid eye drops on the clinical course of patients with stage I pulmonary sarcoidosis, we compared the serum levels of angiotensin converting enzyme (ACE) and bilateral hilar lymphadenopathy (BHL) on chest radiographs of group CS, which is consisted of patients who received topical therapy of betamethasone in the form of eye drops for anterior uveitis, and group CN, which is consisted of patients who did not receive any medications throughout the entire course of the disease. Although the serum ACE level was not significantly different between groups CS and CN at the time of the diagnosis of pulmonary sarcoidosis, the level of serum ACE in group CS was significantly higher than that in group CN 20 months after the topical corticosteroid treatment (24 IU/ml and 16 IU/ml, respectively). Further, the size of BHL on chest radiography in group CS was significantly larger than that in group CN 20 months after the topical treatment (82% and 37% of before control, respectively). These findings suggest the possibility that the topical corticosteroid therapy influenced the clinical course of pulmonary sarcoidosis, inducing some delay in the spontaneous remission in the longterm course.

Adrenal Cortex Hormones↗

PubMed2004

[Death from asthma attacks in Tohoku District. Results from questionnaire surveyed from 1992 to 2001].

In Tohoku district, death from asthma attacks was surveyed from 1992 to 2001. After presence of death from asthma attacks during the previous year were confirmed by post card at the beginning of every February, details of each case were asked by questionnaire. In total, 299 cases (male: 186, female: 113) were recognized as death from asthma attacks. Middle-aged and older asthmatics over 50 year accounted for 2/3 of the cases and the most death was recorded in asthmatics in the second decade of life under 50. Out-patients accounted for 78%. When they visited hospitals, 60% was in cardio-pulmonary arrest and 89% was in more critical condition than severe attacks. About duration of attacks from the onset to their death, within 2 hrs accounted for 25.6%, within 1 day did for 39.6%, and over 1 day did for 34.8%. Although the most death was found in patients whose duration of asthma was between 1 and 10 years, 16 cases died within 1 year from the onset of their asthma. About severity during the past year, 34% had severe asthma, 45% moderate, and 21% mild. Number of death from asthma attacks in Tohoku district was clearly reduced over the past 5 years. The number was reduced to about one-fourth of that at the beginning of survey.

Adolescent↗

PubMed2003

Histogenesis of hepatoid adenocarcinoma of the stomach: molecular evidence of identical origin with coexistent tubular adenocarcinoma.

Hepatoid adenocarcinoma of the stomach is a highly malignant neoplasm. Most gastric hepatoid adenocarcinomas coexist with tubular adenocarcinoma. However, the relationship between hepatoid adenocarcinoma and tubular adenocarcinoma is still unclear. In the present study, the characteristics of the coexistent tubular adenocarcinomas were determined by examining their profiles of mucin production. Subsequently, molecular pathological techniques were applied to determine the clonality of 15 mixed hepatoid and tubular adenocarcinomas of the stomach. Mucin analysis suggested that the coexistent tubular adenocarcinomas with hepatoid adenocarcinoma were of the intestinal type. The patterns of chromosome X inactivation were identical between the hepatoid adenocarcinoma component and tubular adenocarcinoma component in all of 3 informative female cases. Mutations in the p53 gene were found in 5 cases. The sequences were identical within both tumor components in all 5 cases. Microsatellite analysis indicated more than 3 common patterns of loss of heterozygosity in 8 cases. These observations strongly suggested that hepatoid adenocarcinomas were of identical origin to coexistent tubular adenocarcinomas.

Adenocarcinoma↗

PubMed2003

Age-related methylation of tumor suppressor and tumor-related genes: an analysis of autopsy samples.

Age-related methylation may have the potential to behave as a mutator process. To clarify the physiological consequence of age-related methylation of tumor suppressor and tumor-related genes, we studied promoter methylation status in non-neoplastic cells of various organs obtained at autopsy by methylation-specific PCR. Promoter methylation status of APC, DAP-kinase, E-cadherin, GSTP1, hMLH1, p16, RASSF1A and RUNX3 genes, which are frequently silenced in certain human malignancies, was studied in non-neoplastic cells of the esophagus, stomach, small and large intestines, liver, pancreas, kidney and lung obtained from 38 Japanese autopsies. The tumor suppressor and tumor-related genes, except APC and RASSF1A, were generally unmethylated in samples obtained from people who were less than 32 years old (n=11). Methylated promoters were present at variable frequencies in a tissue-specific manner in samples obtained from people who were greater than 42 years old (n=27), although GSTP1 and hMLH1 methylation was absent or infrequent and lacked tissue specificity. In the majority of organs, the incidence of age-related methylation paralleled the reported methylation incidence in malignant counterparts. Thus, age-related methylation of a different set of genes is thought to constitute a field defect in different organs.

Adaptor Proteins, Signal Transducing↗

PubMed2003

Oligodeoxynucleotides without CpG motifs work as adjuvant for the induction of Th2 differentiation in a sequence-independent manner.

The outcomes of immune responses are regulated by various parameters including how Ags are handled by APCs. In this study, we describe the intrinsic immunomodulatory characteristics of oligodeoxynucleotides (ODNs) that improve the Ag presentation by APCs. ODNs (20-mer) containing CpG motifs induced strong Th1-skewed responses. In contrast, those without CpG motifs enhanced cytokine production by effector Th cells without particular skewing toward Th1 responses or induced the differentiation of unprimed CD4(+) T cells toward Th2 cells. These functional features were prominently envisaged when ODNs were conjugated to the Ag, and were underlain by the facilitated binding of ODN-conjugated Ag to Ia(+) cells. Despite the functional differences between ODNs with CpG motifs and those without CpG motifs, both ODNs bound to Ia(+) cells with similar affinity and kinetics. Immunoenhancing activities of the ODNs were not sequence-dependent; the characteristics, including the facilitation of Ag capture, enhancement of effector Th cell responses, and induction of Th2 cells, were shared by randomly synthesized ODNs conjugated to Ag. This is the first study suggesting that ODNs, independent of the sequences, enhance immune responses through the promoted capture of ODN-conjugated Ag by APCs.

Adjuvants, Immunologic↗

PubMed2003

Hypermethylation of the RUNX3 gene promoter in testicular yolk sac tumor of infants.

Testicular yolk sac tumor (YST) of infants is biologically distinct from its adult counterpart. Cytogenetically, YSTs in infants generally lack i(12p), which is highly characteristic of adult germ cell tumors (GCTs), whereas they frequently show a deletion of 1p36, indicating that the loss of a certain gene(s) in this region is an important event in the pathogenesis of infantile YSTs. In the present study, we examined 10 testicular YSTs from infants for promoter methylation status of the RUNX3 gene, localizing in 1p36.1, and loss of heterozygosity (LOH) in this region, on the presumption that RUNX3 acts as a tumor suppressor. Methylation of RUNX3 and LOH at 1p36.1 were detected in 8 of 10 (80%) and 6 of 8 (75%) infantile YSTs examined, respectively. All six cases harboring LOH showed RUNX3 methylation. In contrast, 0 of 12 adult GCTs showed RUNX3 methylation, and LOH at 1p36.1 was less frequent (1 of 6 cases: 16%) in adult GCTs. There is a significant difference in RUNX3 methylation between these 2 groups (P < 0.001). In normal testes of the young group, RUNX3 methylation was not detected. These results strongly suggest that RUNX3 is one of the tumor suppressors involved in the pathogenesis of testicular YSTs in infants.

Adult↗

PubMed2003

Microsatellite instability in esophageal squamous cell carcinoma is not associated with hMLH1 promoter hypermethylation.

To test whether a subset of esophageal squamous cell carcinomas (SCC) develop through a deficiency in DNA mismatch repair, we examined microsatellite instability (MSI) using 11 microsatellite markers including BAT-26, hMLH1 protein expression by immunohistochemistry, and methylation status of the hMLH1 promoter by methylation-specific polymerase chain reaction (MSP). p53 mutations were also investigated. Microsatellite instability at one or more loci was observed in 40% (12/30) of esophageal SCC tumor samples, although only one of these tumors was categorized as high-frequency MSI (MSI-H) and none showed BAT-26 instability. While immunohistochemistry revealed decreased hMLH1 protein expression in 27% (8/30) of the tumors, hMLH1 promoter hypermethylation was not observed. Absence of hMLH1 protein expression was relatively common in well-differentiated (keratinizing-type) esophageal SCC, but was not associated with hMLH1 promoter hypermethylation. p53 mutation was detected in 37% (11/30) and loss of heterozygosity (LOH) in 90% (27/30) of esophageal SCC samples. Our results suggested that most esophageal SCC develop through defects in tumor suppressor genes (i.e. the suppressor pathway), and that MSI in esophageal SCC probably represent random replication errors rather than being associated with DNA mismatch repair deficiency.

Adaptor Proteins, Signal Transducing↗

PubMed2003

Genetic analysis of cutaneous squamous cell carcinomas arising from different areas.

Although cutaneous squamous cell carcinomas (SCC) occur most frequently in sun-exposed areas of the skin, they can also arise in non-sun-exposed areas. Some risk factors for cutaneous SCC, such as ultraviolet (UV) light, are well known. However, the major factor for carcinogenesis may depend on the site of the tumor as well as the ethnicity of the patient. In this study we examined 41 Japanese cutaneous SCC cases, focusing on the area of appearance and the presence of genetic alteration, with 27 cases from sun-exposed areas, 10 from non-sun-exposed areas (excluding genital areas), and four from burn scars from sun-exposed areas. Squamous cell carcinomas arising in sun-exposed areas showed less frequent p53 gene mutations compared to SCC arising in non-sun-exposed areas. Ultraviolet light-specific mutations were found in only two cases of SCC from sun-exposed areas. Human papilloma virus (HPV) DNA was detected in two cases (7.4%) of the sun-exposed areas and none of the non-sun-exposed or scar areas. The frequency of loss of heterozygosity on D5S178 in non-sun-exposed SCC was significantly higher than in sun-exposed SCC. Furthermore, the incidence of fractional allelic loss (FAL) was significantly higher in non-sun-exposed SCC than in sun-exposed SCC. Our findings suggest that sun-exposed SCC in Japan may be relatively less involved with p53 mutation, and that non-sun-exposed SCC acquire more genetic alterations than sun-exposed SCC.

Adult↗

PubMed2003

Carcinosarcomas (malignant mullerian mixed tumors) of the uterus and ovary: a genetic study with special reference to histogenesis.

The histogenesis of carcinosarcomas (malignant mullerian mixed tumors) of the female genital tract is still not completely understood. In the present study, several different molecular pathologic techniques were applied to determine the histogenesis of 15 uterine and ovarian carcinosarcomas. The patterns of X-chromosome inactivation and the presence of p53 and K-ras mutations were analyzed in the carcinomatous and sarcomatous components. Microsatellite analysis was also performed. Ten tumors were monoclonal, one was biclonal (collision tumor), and another was probably biclonal; the other three were of indeterminate histogenesis. These data indicate that most uterine and ovarian carcinosarcomas are monoclonal.

Adult↗

PubMed2003

Promoter methylation status of DAP-kinase and RUNX3 genes in neoplastic and non-neoplastic gastric epithelia.

Silencing of tumor suppressor and tumor-related genes by hypermethylation at promoter CpG islands is frequently found in human tumors, including gastric cancer. Promoter methylation is not restricted to cancer cells, and is also present in non-neoplastic cells as an age-related tissue-specific phenomenon. To clarify the physiological consequence of DAP-kinase and RUNX3 age-related methylation in gastric epithelia, we investigated the promoter methylation status of these genes in both neoplastic and non-neoplastic gastric epithelia obtained at autopsy and surgery, as well as in 10 gastric cancer cell lines. Methylation of DAP-kinase and RUNX3 was detected in 10% (1/10) and 70% (7/10) of the cell lines, respectively, and was almost concordant with their expression status. Among autopsy samples, methylation of these genes was not seen in non-neoplastic gastric epithelia from persons who were aged 22 years and below (0%; 0/4). DAP-kinase was methylated in 87% (13/15) of non-neoplastic gastric epithelia of persons who were aged 45 years or older, while RUNX3 methylation in non-neoplastic gastric epithelia was restricted to individuals who were aged 77 years or older. Among samples obtained from patients with stomach cancer, methylation was observed in both the neoplastic and the corresponding non-neoplastic gastric epithelia; 43% (40/93) and 73% (68/93) for DAP-kinase, and 45% (42/93) and 8% (7/93) for RUNX3, respectively. Frequencies of DAP-kinase and RUNX3 methylation differed significantly in non-neoplastic gastric epithelia (P < 0.01), although those in gastric cancers were almost the same. RUNX3 methylation is mostly cancer-specific, except for very old individuals, and therefore may be a possible molecular diagnostic marker and malignancy predictor.

Adenocarcinoma↗

PubMed2003

Promoter hypermethylation of tumor suppressor and tumor-related genes in non-small cell lung cancers.

Aberrant methylation of promoter CpG islands is known to be a major inactivation mechanism of tumor suppressor and tumor-related genes. To determine the clinicopathological significance of gene promoter methylation in non-small cell lung cancer (NSCLC), we examined the promoter methylation status of the APC, DAP-kinase, E-cadherin, GSTP1, hMLH1, p16, RASSF1A and RUNX3 genes in 75 NSCLCs and corresponding non-neoplastic lung tissues by methylation-specific PCR (MSP). The frequencies of methylation in NSCLCs and corresponding non-neoplastic lung tissues were: 37% (28 of 75) and 48% (36 of 75) for APC, 28% (21 of 75) and 13% (10 of 75) for DAP-kinase, 29% (22 of 75) and 15% (11 of 75) for E-cadherin, 1% (1 of 75) and 0% (0 of 75) for GSTP1, 7% (5 of 75) and 0% (0 of 75) for hMLH1, 31% (23 of 75) and 0% (0 of 75) for p16, 43% (32 of 75) and 4% (3 of 75) for RASSF1A, and 20% (15 of 75) and 3% (2 of 75) for RUNX3, respectively. Methylation of p16 was more frequent in squamous cell carcinomas than in adenocarcinomas (P < 0.05), and was associated with tobacco smoking (P < 0.05). On the contrary, methylation of APC and RUNX3 was more frequent in adenocarcinomas than in squamous cell carcinomas (P < 0.05). Thus, a different set of genes is thought to undergo promoter methylation, which leads to the development of different histologies. In addition, methylation of p16, RASSF1A and RUNX3 was mostly cancer-specific (P < 0.05), and may be utilized as a molecular diagnostic marker of NSCLCs.

Adult↗

PubMed2002

B cells capturing antigen conjugated with CpG oligodeoxynucleotides induce Th1 cells by elaborating IL-12.

APCs initiate T cell-mediated immune responses against foreign Ags. Dendritic cells are professional APCs that play unique roles, including Ag-nonspecific capture, priming of naive T cells, and Th1 induction, whereas B cells generally lack these functions. In this study we uncovered novel aspects of murine B cells as APCs using CpG oligodeoxynucleotides (CpG) conjugated with an Ag. B cells served as efficient APCs independently of surface Igs. This characteristic was underlaid by the CpG-mediated Ag uptake and presentation, which were functional only when CpG were covalently conjugated to Ag. The B cells cultured with CpG-conjugated Ag not only enhanced IFN-gamma formation by Th1 cells, but also induced Th1 differentiation from unprimed T cells. These effects paralleled with the increase in the expression of CD40, CD86, and class II molecules on B cells and the coordinated production of IL-12 by the cells. To our knowledge this is the first report revealing that B cells share with dendritic cells common intrinsic characteristics, such as the Ag-nonspecific capture and presentation, and the induction of Th1 differentiation from unprimed T cells.

Animals↗

PubMed2002

Instabilotyping reveals unique mutational spectra in microsatellite-unstable gastric cancers.

Microsatellite instability (MSI) within coding regions causes frameshift mutations (FSMs). This type of mutation may inactivate tumor suppressor genes in cancers with frequent MSI (MSI-H cancers). To identify novel FSMs in gastric carcinogenesis in an unbiased and comprehensive manner, we screened for this type of mutation at 154 coding region repeat loci in 18 MSI-H gastric cancers. We also compared FSM rates and spectra in MSI-H gastric versus colorectal cancers. Thirteen novel loci showed FSMs in >20% of gastric tumors. Novel loci with the highest mutation frequencies included the activin type 2 receptor gene (44.4%), DKFZp564K112 (a homologue of the Drosophila tumor suppressor gene multi-sex-combs; 41.2%), and an endoplasmic reticulum chaperone protein gene SEC63 (37.5%). The mutational spectra for genes with high mutation frequencies were also significantly different between MSI-H gastric and colorectal cancers.

Colorectal Neoplasms↗

PubMed2002

Analysis of genetic and epigenetic alterations of the PTEN gene in gastric cancer.

The PTEN tumor suppressor gene on 10q23.3, responsible for the Cowden and Bannayan-Zonana syndromes, encodes a dual-specificity phosphatase able to dephosphorylate both tyrosine phosphate and serine/threonine phosphate residues. Mutational inactivation of PTEN has been reported in various malignancies, including endometrial cancers, ovarian cancers, and glioblastomas. In this study, we investigated PTEN gene mutations in 10 gastric cancer cell lines and 58 primary gastric cancers by polymerase chain reaction single strand conformation polymorphism (PCR-SSCP). Hypermethylation of promoter region CpG islands, an alternative mechanism of gene inactivation to coding region mutations, was also evaluated by methylation specific PCR (MSP). Only one (1.7%) of the 58 primary tumors carried a somatic 5-bp deletion in intron 7 of PTEN, which did not alter the mRNA sequence, and no mutations were detected in any of the cell lines. Similar levels of PTEN mRNA expression were observed in all cell lines and primary tumors studied by RT-PCR, and PTEN promoter CpG islands remained unmethylated. Therefore, we conclude that PTEN does not participate in gastric carcinogenesis as a tumor suppressor gene.

Adenocarcinoma↗

PubMed2002

Promoter methylation status of E-cadherin, hMLH1, and p16 genes in nonneoplastic gastric epithelia.

Silencing of tumor suppressor and tumor-related genes by hypermethylation at promoter CpG islands is one of the major events in human tumorigenesis. Promoter methylation is also present in nonneoplastic cells as an age-related tissue-specific phenomenon that precedes the development of neoplasia. To clarify the significance of promoter methylation in nonneoplastic gastric epithelia as a precancerous signal, we investigated promoter methylation status of E-cadherin, hMLH1, and p16 genes in nonneoplastic cells of various organs obtained at autopsy, and compared the results with those of nonneoplastic epithelia of a cancerous stomach. Methylation of these genes was not seen in nonneoplastic cells of organs from people who were 22 years and younger (0%, 0 of 6). In contrast, E-cadherin and p16 were methylated in nonneoplastic gastric epithelia of persons who were 45 years or older. The numbers were 86% (12 of 14) and 29% (4 of 14), respectively. E-cadherin methylation occurred preferentially in the intestines, whereas p16 methylation was almost restricted to the stomach. For samples obtained from patients with stomach cancer, methylation was frequently observed in both neoplastic and corresponding nonneoplastic gastric epithelia: 47% (44 of 94) and 67% (63 of 94) for E-cadherin, 32% (30 of 94) and 24% (23 of 94) for hMLH1, and 22% (21 of 94) and 44% (41 of 94) for p16, respectively. hMLH1 methylation was not seen in nonneoplastic gastric epithelia from autopsy samples but occurred significantly in samples from nonneoplastic tissues of individuals with stomach cancer. Therefore, detection of hMLH1 methylation in nonneoplastic gastric epithelia may be useful for screening patients who may be at risk of developing gastric cancer.

Adaptor Proteins, Signal Transducing↗