1
UI - 11695299
AU - Testino G; Testino R; Ancarani AO
TI - [Helicobacter pylori and gastric carcinogenesis]
SO - Recenti Prog Med 2001 Oct;92(10):573-7
AD - Unita Operativa di Gastroenterologia, Azienda Ospedale San Martino, Genova.
Gastric carcinogenesis is a multistep and multifactorial process beginning with chronic gastritis Helicobacter pylori (Hp) induced in most cases. There are some obstacles to an exclusive acceptance of the idea that the relation of Hp with the preneoplastic/neoplastic changes solely develops by means of the chronic gastritis with its atrophic evolution and achlorydria. Hp may be considered a trigger by means of alteration of cellular synetics without any direct influence on genetic alterations. Under the push of an intense proliferation, the expression of typical antigens of the organ is progressively lost, with acquisition of antigens from other organs. Cellular dedifferentiation displayed, with the progressive increase of immature elements that progress to the more or less total disappearance of differentiated gastric cells or differentiating ones, with the formation of metaplastic/dysplastic clones or even neoplastic ones. The bacteria, together with other environmental factors and individual genetic susceptibility, determine the final risk for the development of gastric cancer. Considering that 1-2% of the Hp positive subjects are estimated to develop gastric cancer and that Hp is considered the cause of 75% of gastric cancer, the eradication of the infection, not only in the initial phases but even in those with preneoplastic changes, involves an advantage for the prevention of gastric cancer. For the prevention among the general population testing Hp-positive subjects for serum antibodies against CagA protein might represent an effective way of identifying patients in whom Hp eradication is advisable also in term of gastric cancer prevention.

2
UI - 11972277
AU - Szanto I; Voros A; Nagy P; Gonda G; Gamal EM; Altorjay A; Banai J; Kiss
TI - J Esophageal intramural metastasis from adenocarcinoma of the gastroesophageal junction.
SO - Endoscopy 2002 May;34(5):418-20
AD - Department of Surgery, Faculty of Health Sciences, Semmelweis University, Budapest, Hungary. szantoimre@freemail.hu
Among a total of 143 patients examined for diagnosis of adenocarcinoma of the cardia, intramural esophageal metastases were verified in six patients (4.19 %). In each case the diagnosis was confirmed by histological examination. The histological structure of the primary tumors and metastases was the same. Metastases were detected by endoscopic ultrasound examination in three cases. All the cardia tumors proved to be well advanced. As well as endoscopic identification of the primary tumor, thorough examination of the proximal part of the esophagus is of great importance.

3
UI - 12037037
AU - Roberts PJ; Dickinson RJ; Whitehead A; Laughton CR; Foweraker JE
TI - The culture of lactobacilli species in gastric carcinoma.
SO - J Clin Pathol 2002 Jun;55(6):477

4
UI - 12037664
AU - Koo TH; Lee JJ; Kim EM; Kim KW; Kim HD; Lee JH
TI - Syntenin is overexpressed and promotes cell migration in metastatic human breast and gastric cancer cell lines.
SO - Oncogene 2002 Jun 13;21(26):4080-8
AD - Anti-Cancer Research Laboratory, Korea Research Institute of Bioscience and Biotechnology, P.O. Box 115, Yuseong, Daejeon 305-600, Korea.
Two human breast cancer cell lines of differing invasive and metastatic potential, MDA-MB-435 and MCF7, were examined using subtractive suppression hybridization in a search for any genes associated with metastasis. Of the 17 cDNAs identified as being differentially expressed genes, it was determined that syntenin was overexpressed in metastatic MDA-MB-435 cells. Expression analysis showed that the expression level of syntenin was well correlated with invasive and metastatic potential in various human breast and gastric cancer cell lines. Moreover, gastric tumor tissues exhibited a much higher syntenin mRNA expression than their normal counterparts. Syntenin-transfected MCF7 cells migrated more actively, and showed an increased invasion rate relative to vector-transfectants or parental MCF7 in vitro, without evidencing any effect on the adhesion to fibronectin, type I collagen and laminin. Similarly, the forced expression of syntenin to human gastric cancer cell line Az521 increased its migratory and invasive potential in vitro. Syntenin-expressing MCF7 cells were associated with the appearance of numerous cell surface extensions and with pseudopodia formation on collagen I, suggesting that syntenin may be involved in the signaling cascade to actin-reorganization. Mutation study suggested that PDZ2 domain of syntenin could be an essential role in its stimulatory effect on the cell migration. This is the first demonstration that syntenin, a PDZ motif-containing protein, can be overexpressed during the metastatic progression of human breast and gastric cancer cells and that it can function as a metastasis-inducing gene.

5
UI - 12037667
AU - Peng YF; Mandai K; Nakanishi H; Ikeda W; Asada M; Momose Y; Shibamoto S;
TI - Yanagihara K; Shiozaki H; Monden M; Takeichi M; Takai Y Restoration of E-cadherin-based cell-cell adhesion by overexpression of nectin in HSC-39 cells, a human signet ring cell gastric cancer cell line.
SO - Oncogene 2002 Jun 13;21(26):4108-19
AD - Department of Molecular Biology and Biochemistry, Osaka University Graduate School of Medicine/Faculty of Medicine, Suita 565-0871, Japan.
Nectin is an immunoglobulin-like adhesion molecule that comprises a family consisting of four members, nectin-1, -2, -3, and -4. Nectin is associated with the actin cytoskeleton through afadin, a nectin- and actin filament-binding protein. The nectin-afadin and cadherin-catenin systems are associated with each other and cooperatively form cell-cell adherens junctions in intact epithelial cells. HSC-39 cells, a human signet ring cell gastric cancer cell line, express E-cadherin but do not form cell-cell adhesion. The beta-catenin gene has been shown to be truncated at the N-terminal region including the alpha-catenin-binding domain in HSC-39 cells, but overexpression of normal beta-catenin failed to form cell-cell adhesion. HSC-39 cells expressed nectin-1, -2, and afadin, but not nectin-3. Overexpression of nectin-3 or -2 formed cell-cell adhesion and accumulation of E-cadherin, but not actin filaments, at the cell-cell adhesion sites. Overexpression of a truncated form of nectin-2 incapable of interacting with afadin failed to form cell-cell adhesion. However, the nectin-formed cell-cell adhesion was not so strong as that observed in epithelial cells, such as CaCo-2 cells. Co-expression of nectin-2 and normal beta-catenin did not form strong cell-cell adhesion. These results suggest that an unidentified mechanism, by which nectin and E-cadherin form the actin cytoskeleton-associated adherens junctions to form strong cell-cell adhesion, is impaired in HSC-39 cells.

6
UI - 12064868
AU - Qvigstad G; Qvigstad T; Westre B; Sandvik AK; Brenna E; Waldum HL
TI - Neuroendocrine differentiation in gastric adenocarcinomas associated with severe hypergastrinemia and/or pernicious anemia.
SO - APMIS 2002 Feb;110(2):132-9
AD - Norwegian University of Science and Technology, Faculty of Medicine, Department of Intra-abdominal Diseases, Trondheim.
Patients with hypergastrinemia secondary to achlorhydria have an increased risk of developing ECL cell carcinoids and gastric adenocarcinomas. Hypergastrinemia is central in the pathogenesis of ECL cell carcinoids, but the link between gastrin and gastric carcinomas is controversial. During neoplastic transformation ECL cells may, however, lose many of their neuroendocrine characteristics, making them difficult to recognise as neuroendocrine with conventional immunohistochemical techniques. Neuroendocrine differentiation was therefore examined in eight gastric adenocarcinomas found in seven patients with severe hypergastrinemia and/or pernicious anemia using a monoclonal antibody towards chromogranin A and immunohistochemistry without and with a sensitive signal amplification technique. The Sevier-Munger method was used as a more specific marker of ECL cells. Seven of the carcinomas contained scattered neuroendocrine tumour cells. When using signal amplification, an increase in the number of immunoreactive neoplastic cells was seen. In many tumours, clusters or confluent sheets of such cells were disclosed, suggesting a neuroendocrine and ECL cell origin. These tumours may therefore be ECL cell carcinomas and hypergastrinemia may thus be involved in the tumourigenesis.

7
UI - 12001647
AU - Sihvo E; Salo J
TI - [Malign complication of gastroesophageal reflux: adenocarcinoma of esophagus and gastric cardia]
SO - Duodecim 2000;116(17):1907-11
AD - HUS:n kirurgian klinikka Haartmaninkatu 4, 00029 HUS.

8
UI - 12086398
AU - Kim H; Lim JW; Seo JY; Kim KH
TI - Oxidant-sensitive transcription factor and cyclooxygenase-2 by Helicobacter pylori stimulation in human gastric cancer cells.
SO - J Environ Pathol Toxicol Oncol 2002;21(2):121-9
AD - Department of Pharmacology and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea. kim626@yumc.yonsei.ac.kr
Helicobacter pylori (H. pylori) infection might activate nuclear factor-kappaB (NF-kappaB), an oxidant-sensitive transcription regulator of inducible expression of inflammatory genes such as cyclooxygenase-2 (COX-2). We studied the role of NF-kappaB on expression of COX-2 in H. pylori-stimulated gastric cancer cell lines by using antioxidants, glutathione (GSH), and N-acetylcysteine (NAC) as well as an NF-kappaB inhibitor, pyrrolidine dithiocarbamate (PDTC). Gastric adenocarcinoma cell lines derived from Caucasian (AGS) cells and Korean (SNU-484) cells were used to study the role of NF-kappaB on COX-2 expression by H. pylori. They were treated with GSH, NAC, or PDTC in the presence of H. pylori. mRNA expression and protein level for COX-2 were determined by Northern blot and RT-PCR analysis as well as Western blot analysis. NF-kappaB activation was examined by electrophoretic mobility shift assay. As a result, H. pylori induced a time-dependent expression of mRNA and protein for COX-2 via activation of NF-kappaB, which was inhibited by GSH, NAC, and PDTC in the cells. In conclusion, oxidant-sensitive transcription factor NF-kappaB may play a novel role in expression of COX-2 by H. pylori stimulation in gastric cancer cells.

9
UI - 11986338
AU - Ranaldi R; Goteri G; Baccarini MG; Mannello B; Bearzi I
TI - A clinicopathological study of 152 surgically treated primary gastric lymphomas with survival analysis of 109 high grade tumours.
SO - J Clin Pathol 2002 May;55(5):346-51
AD - Department of Pathology, University of Ancona School of Medicine, 60020 Torrette di Ancona, Italy.
AIMS: To describe the clinicopathological features of a large number of surgically treated and followed up primary gastric lymphomas and thereby gain a better understanding of their biology, with particular reference to the prognostic factors of high grade tumours. METHODS: A retrospective study of 152 patients. RESULTS: High grade gastric lymphomas, both pure and with a residual low grade component, differed from low grade mucosa associated lymphoid tissue (MALT)-type lymphomas in that they were more frequently large, ulcerated, at an advanced stage, and highly proliferating. In addition, patients were older and had a worse outcome. The prognosis of high grade lymphomas was influenced by patient age, tumour stage, depth of infiltration in the gastric wall, and the invasion of adjacent organs. Adjuvant postsurgical treatment prolonged survival only in patients with advanced stage and deep neoplastic infiltration. CONCLUSIONS: There is a sharp distinction between low grade MALT-type lymphomas and tumours with a high grade component, justifying their different treatment approach. The postsurgical management of high grade lymphomas should be based on the accurate evaluation of the neoplastic extension.

10
UI - 12075175
AU - Matsumoto M; Natsugoe S; Ishigami S; Nakashima S; Nakajo A; Miyazono F;
TI - Hokita S; Takao S; Eizuru Y; Aikou T Lymph node micrometastasis and lymphatic mapping determined by reverse transcriptase-polymerase chain reaction in pN0 gastric carcinoma.
SO - Surgery 2002 Jun;131(6):630-5
AD - First Department of Surgery, Kagoshima University School of Medicine, Japan.
BACKGROUND: The purposes of this study were to examine lymph node micrometastasis (LMM) by reverse transcriptase-polymerase chain reaction (RT-PCR) method, and clarify the initial nodes involved by metastatic disease according to tumor location. METHODS: We examined 312 lymph nodes obtained from 50 patients with node-negative gastric carcinoma. RT-PCR and immunohistochemistry were performed. The clinical characteristics of LMM were investigated, and the map of LMM was made according to tumor location. RESULTS: The number of patients and LMM detected by RT-PCR was 14 and 17 and by immunohistochemistry was 7 and 8, respectively. RT-PCR was a more sensitive method than immunohistochemistry. LMM by RT-PCR correlated with depth of tumor invasion and lymphatic invasion. Regarding pT1 tumor, 9 patients with LMM had tumors that were of the macroscopically depressed type and 2 cm or more in diameter. According to the lymphatic map, right pericardial lymph nodes and lymph nodes along the lesser curvature were the initial nodes involved in the upper third of the stomach. Right pericardial lymph nodes, lymph nodes along the lesser curvature, and infrapyloric nodes were more important initial metastatic sites in the middle third of the stomach, and lymph nodes along the lesser curvature and infrapyloric nodes in the lower third. CONCLUSIONS: We demonstrated the relationship between LMM and clinicopathologic factors, especially in pT1 tumor. The mapping of LMM may prove useful for selecting the optimal treatment.

11
UI - 11966873
AU - Wambura C; Aoyama N; Shirasaka D; Sakai T; Ikemura T; Sakashita M;
TI - Maekawa S; Kuroda K; Inoue T; Ebara S; Miyamoto M; Kasuga M Effect of Helicobacter pylori-induced cyclooxygenase-2 on gastric epithelial cell kinetics: implication for gastric carcinogenesis.
SO - Helicobacter 2002 Apr;7(2):129-38
AD - Second department of Internal medicine and Department of Endoscopy, Kobe University School of Medicine, Japan.
BACKGROUND: Cyclooxygenase (COX)-2 induced by Helicobacter pylori is thought to enhance gastric carcinogenesis by affecting the maintenance of epithelial homeostasis. MATERIALS AND METHODS: Gastric biopsies from 160 subjects, 97 with nonulcer dyspepsia (47 H. pylori negative, 50 H. pylori positive) and 63 with gastric cancer were examined immunohistochemically for COX-2 expression, cell proliferation and apoptotic indices. RESULTS: COX-2 expression in corpus was significantly higher in H. pylori positive than in negative non-ulcer dyspepsia (NUD) (p <.05). Regardless of site, gastric cancer subjects had higher COX-2 expression in both antrum and corpus compared with H. pylori negative and positive NUD (p <.005). Proliferation was higher in cancer and H. pylori positive than in negative NUD (p <.0001). Moreover, cancer had enhanced proliferation than H. pylori positive NUD in corpus greater (p =.0454) and antrum lesser (p =.0215) curvatures. Apoptosis was higher in H. pylori positive than in negative NUD (p <.05). However, both had a higher index than the cancer subjects (p <.0001). Apoptosis : proliferation ratio was higher in corpus of H. pylori negative than in positive NUD in greater (p =.0122) and lesser (p =.0009) curvatures. However, both had a higher A:P ratio than cancer cases (p =.0001). A negative correlation between COX-2 expression and A:P ratio was found in corpus greater (r = -.176, p =.0437) and lesser (r = -.188, p =.0312) curvatures. CONCLUSION: The expression of COX-2 is associated with disruption in gastric epithelial kinetics and hence may play a role in gastric carcinogenesis.

12
UI - 12019175
AU - Mashino K; Sadanaga N; Yamaguchi H; Tanaka F; Ohta M; Shibuta K; Inoue
TI - H; Mori M Expression of chemokine receptor CCR7 is associated with lymph node metastasis of gastric carcinoma.
SO - Cancer Res 2002 May 15;62(10):2937-41
AD - Department of Surgery, Medical Institute of Bioregulation, Kyushu University, 4546 Tsurumibaru, Beppu 874-0838, Japan.
The interactions of chemokine receptor CCR7 and its ligands are essential for migration of lymphocytes and dendritic cells to lymph nodes. In this study, we found that 4 of 6 (67%) gastric carcinoma cell lines tested expressed functional CCR7 for the chemokine CCL21/6Ckine, as demonstrated by calcium mobilization and actin polymerization assays. Moreover, we also showed that signaling through CCR7 induced chemotactic and invasive responses in CCR7-positive gastric carcinoma cells. In clinical samples, immunohistochemical assay showed that CCR7-positive carcinoma cells were detected in 42 of 64 (66%) cases and a significant difference in both lymph node metastasis (P < 0.001) and lymphatic invasion (P < 0.001) between CCR7-positive and -negative cases. Patients with CCR7-positive tumors had a significantly poorer prognosis than those with CCR7-negative tumors (P < 0.05). Stepwise regression analysis revealed that the most important factor related to lymph node metastasis was the expression of CCR7. These results indicated that CCR7 and its ligands interaction is associated with preferential lymph node metastasis of gastric carcinoma.

13
UI - 12081203
AU - Candusso ME; Luinetti O; Villani L; Alberizzi P; Klersy C; Fiocca R;
TI - Ranzani GN; Solcia E Loss of heterozygosity at 18q21 region in gastric cancer involves a number of cancer-related genes and correlates with stage and histology, but lacks independent prognostic value.
SO - J Pathol 2002 May;197(1):44-50
AD - Department of Pathology, IRCCS Policlinico San Matteo and University of Pavia, Italy.
Several studies support a role of 18q21 LOH, involving the DCC locus, in colorectal cancer progression; however, its contribution to the natural history of gastric cancer is less clear. Recently, a number of cancer-related genes have been mapped in the 18q21 region, either centromeric or telomeric to DCC. This study searched for 18q21 LOH in 161 gastric cancers representative of all tumour stages and main histological types. To this purpose, seven highly polymorphic markers were used flanking the 18q21 band and spanning the entire region. Thirty-four out of 147 (23.1%) informative cases showed LOH. In 27 of 34 cases (79%), LOH involved all the informative loci. The remaining seven cases showed LOH at more telomeric sites and retained heterozygosity at more centromeric markers, mostly those proximal to the DCC gene. A strong correlation between 18q21 LOH and level of gastric wall invasion, lymph node metastases, or stage was found in cohesive (glandular+solid) and mixed tumours, but not in diffuse cancers. Cox univariate and multivariate analysis showed that invasion level, lymph node metastases, distant metastases, TNM stage, and histology were effective predictors of survival, whereas 18q21 LOH did not show predictive power. The simultaneous deletion of a variety of cancer-related genes with different and even opposite roles might explain why, apparently, 18q21 LOH does not per se contribute significantly to the natural history of gastric cancer, despite strong correlation with stage.

14
UI - 12055676
AU - Chang MS; Kim HS; Kim CW; Kim YI; Lan Lee B; Kim WH
TI - Epstein-Barr virus, p53 protein, and microsatellite instability in the adenoma-carcinoma sequence of the stomach.
SO - Hum Pathol 2002 Apr;33(4):415-20
AD - Department of Pathology and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
To elucidate the adenoma-carcinoma sequence in the stomach, we investigated Epstein-Barr virus (EBV) incorporation, p53 overexpression, and microsatellite instability (MSI) in gastric adenomas and carcinomas. The study involved 66 cases of gastric carcinomas within or adjacent to adenomas (adenoma-carcinoma cases), 81 cases of simple adenomas (without carcinoma), and 306 de novo carcinomas (without adenoma focus). EBV incorporation was revealed in 1 (1.5%) of the adenoma-carcinomas, in none of the adenomas, and in 17 (5.6%) of the de novo carcinomas. p53 overexpression was observed in 24.2% (16 of 66) of the adenomas in the adenoma-carcinoma cases and in 36.5% (23 of 63) of corresponding carcinomas (kappa = 0.63, P = 0.00). MSI was positive in 12.3% (8 of 65) of the adenomas in the adenoma-carcinoma cases and in 18.8% (12 of 64) of the corresponding carcinomas (kappa = 0.77, P = 0.00). In conclusion, EBV incorporation is not possibly associated with the gastric adenoma-carcinoma sequence, whereas the gastric adenoma-carcinoma sequence seems to be supported in terms of p53 overexpression or MSI. The transcriptional activation of EBV may occur relatively late (after the adenoma stage) in the gastric adenoma-carcinoma sequence. Copyright 2002, Elsevier Science (USA). All rights reserved.

15
UI - 11966533
AU - Czopek J; Bialas M; Rudzki Z; Zazula M; Pituch-Noworolska A; Zembala M;
TI - Popiela T; Kulig J; Kolodziejczyk P; Stachura J The relationship between gastric cancer cells circulating in the blood and microsatellite instability positive gastric carcinomas.
SO - Aliment Pharmacol Ther 2002 Apr;16 Suppl 2():128-36
AD - Department of Pathology, Jagiellonian University Medical College, Krakow, Poland.
BACKGROUND: Cancers characterized by microsatellite instability may be biologically different from their counterparts with stable microsatellite sequences. Circulating cancers cell present in blood prior to surgery may constitute an adverse prognostic finding. AIM: To correlate these two phenomena with morphological features and survival in advanced gastric cancer. METHODS: We examined 76 cases of resected sporadic, advanced gastric cancer by means of routine morphology and a panel of microsatellite markers. Sixty-six cases were screened for presence of cancer cells circulating in blood prior to the surgery using combined morphological and immunocytochemical approach. RESULTS: Twenty-one (27.6%) cases demonstrated microsatellite instability in at least one locus. Among them 11 (14.5%) showed microsatellite instability in more than 30% (4/12) examined loci, and they were therefore designated as replication error positive (RER+). Circulating cancer cells were detected in 2/19 microsatellite instability and in 11/47 remaining cases (difference not significant). The survival of the microsatellite instability cases was significantly better. The presence of circulating cancer cells did not correlate with survival. CONCLUSION: It is possible that the microsatellite instability status, but not circulating cancer cells, constitutes a prognostic predictive factor in advanced gastric carcinoma. Confirmation of this hypothesis requires continuation of patient follow-up.

16
UI - 11966535
AU - Sepulveda AR; Tao H; Carloni E; Sepulveda J; Graham DY; Peterson LE
TI - Screening of gene expression profiles in gastric epithelial cells induced by Helicobacter pylori using microarray analysis.
SO - Aliment Pharmacol Ther 2002 Apr;16 Suppl 2():145-57
AD - Department of Pathology, University of Pittsburgh, PA 15213-2582, USA. sepulvedaar@msx.upmc.edu
BACKGROUND: H. pylori infection is a major risk factor in gastric cancer development. The availability of cDNA microarrays creates the unprecedented opportunity to examine simultaneously dynamic changes of multiple pathways affected by H. pylori infection. AIM: In this study we examined broad patterns of gene expression induced by H. pylori in the gastric cancer cell line 1739-CRL AGS cells in culture using the U95A microarray. METHODS: H. pylori were cocultured with AGS cells for 4, 12, 24 and 48 h. Total RNA was extracted and after labelling was used for detection of genes represented in the human U95A microarray set. Data analyses were performed using GeneChip and CLUSFAVOR software. RESULTS: Nearly 6000 genes present in the array were expressed by AGS cells. We report approximately 200 genes that showed the most marked changes. Our studies confirm the up-regulation of c-jun, jun-B, c-fos and cyclin D1 by H. pylori. We report for the first time the induction of the serine threonine kinase pim-1 and ATF3 by H. pylori infection of AGS cells. CONCLUSIONS: In this microarray analysis of gene expression induced by H. pylori in gastric epithelial cells, we identified a large number of unsuspected genes affected by H. pylori. Further, we show that unsupervised hierarchical cluster analysis can provide useful insight into the possible contribution of genes in specific pathways, based on their profile of expression.

17
UI - 11938779
AU - Zou Y; Wu G; Feng D
TI - [Changes on positive rate and distribution of Helicobacter pylori during progression of gastric cancer]
SO - Hunan Yi Ke Da Xue Xue Bao 1999;24(2):161-3
AD - Division of Gastroenterology, Xiangya Hospital, Hunan Medical University, Changsha 410008.
We observed changes on the positive rate and the distribution of helicobacter pylori (HP) in 7 case during early stage of gastric cancer and in 42 cases during middle-late stage of gastric cancer. The results showed that 1. the positive rate during early stage of gastric cancer was 57.1%, the positive rate during middle-rate stage of gastric cancer was 23.8%, 2. HP was not found within the gastric cancer lesions, 3. for HP positive cases, HP distribution during early stage of gastric cancer was more sparse than during middle-late stage of gastric cancer. These results suggested that HP can hardly live within the gastric cancer tissue, so the progression of gastric cancer is probably independent of HP. It may be a question that HP eradication can prevent later development of gastric cancer.

18
UI - 12094696
AU - Yasui W; Oue N; Kuraoka K; Nakayama H
TI - [Molecular diagnosis of gastric cancer]
SO - Nippon Geka Gakkai Zasshi 2002 Jun;103(6):463-7
AD - Department of Molecular Pathology, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan.
Based on the genetic and epigenetic abnormalities of cancer-related genes during the development and progression of gastric cancer, we have established a system of molecular-pathological diagnosis as a routine service in Hiroshima. Approximately 5,000 lesions of the stomach have been diagnosed and useful information on differential diagnosis, grade of malignancy, and tumor multiplicity has been obtained using this system. Further research on systemic gene expression profiles, epigenetic alterations, and genetic polymorphisms will improve the quality and efficiency of diagnosis. With the application of novel knowledge on molecular carcinogenesis and microarray techniques, molecular diagnosis will identify the characteristics of individual cancers and persons, which will lead to the development of personalized medicine.

19
UI - 11837120
AU - Meijer van Putten JB
TI - [Helicobacter pylori]
SO - Ned Tijdschr Tandheelkd 1995 Aug;102(8):327-8

20
UI - 11986192
AU - Schwarz RE; Zagala-Nevarez K
TI - Recurrence patterns after radical gastrectomy for gastric cancer: prognostic factors and implications for postoperative adjuvant therapy.
SO - Ann Surg Oncol 2002 May;9(4):394-400
AD - Department of General Oncologic Surgery, City of Hope National Medical Center, Duarte, California, USA. r.schwarz@umdnj.edu
BACKGROUND: A recent Intergroup trial demonstrated a significant survival advantage of postgastrectomy chemoradiation in gastric cancer patients, primarily because of a reduction of a relative locoregional recurrence (LRR) rate exceeding 70% in control patients. Radical gastrectomy with extended lymphadenectomy may reduce LRR, possibly affecting adjuvant treatment strategies. METHODS: Information on patients undergoing gastrectomy for potentially curable gastric cancer between 1990 and 2000 was reviewed. Patterns of first disease recurrence, survival, and disease-free survival were calculated, and predictors were identified. RESULTS: Gastrectomies were performed in 73 patients, with R0 resections in 82%. The median lymph node count was 24; positive nodes were found in 64% of patients. The median actuarial survival was 27 months, with a 5-year survival of 37%. Disease recurred in 35 patients (48%) after a median interval of 7 months (range,.5-67). Recurrent disease patterns included distant only (37%), peritoneal only (23%), peritoneal/locoregional (17%), all sites combined (14%), locoregional only (6%), and distant/locoregional (3%). Recurrence predictors were N3 category for distant recurrence (hazard ratio [HR], 10.2; P =.005), T3/4 category for peritoneal recurrence (HR, 4.8; P =.008), peritoneal relapse (HR, 40; P =.002), and a prior abdominal operation for LRR (HR, 3.2; P =.01). N2 disease had a distant failure risk similar to N1 status and an intraperitoneal failure risk similar to an N3 category. CONCLUSIONS: Isolated LRR of gastric cancer after gastrectomy and extended lymphadenectomy is rare in this series. Most recurrences appeared diffusely at distant or peritoneal sites, and most LRRs occurred in conjunction with relapse at extraregional sites. Pathologic predictors of intraperitoneal (T3/4) or systemic failure (>N1) could be used to guide individualized, risk-oriented, adjuvant treatment.

21
UI - 12053797
AU - Lasser P
TI - [Stomach tumors]
SO - Rev Prat 2002 Apr 15;52(8):869-75
AD - Service de chirurgie digestive carcinologique de l'Institut Gustave-Roussy, 94805 Villejuif.

22
UI - 12008202
AU - Carvalho B; Seruca R; Buys CH; Kok K
TI - Novel expressed sequences obtained by means of a suppression subtractive hybridisation analysis from the 6q21 region that is frequently deleted in gastric cancer.
SO - Eur J Cancer 2002 May;38(8):1126-32
AD - Instituto de Patologia e Imunologia Molecular da Universidade do Porto, IPATIMUP, Oporto, Portugal.
In our search for genomic regions that are involved in the development of gastric cancer, we recently identified a 2-cM minimal region of overlapping heterozygous deletions in 6q16.3-q23.1. Here, we describe an application of the suppression subtraction method (SSH) to search for genes in this small region of the genome, taking advantage of the fact that many human genes present on yeast artificial chromosomes (YACs) are expressed in yeast. Subtraction was performed with two virtually contiguous YACs that cover a region of approximately 2.5 Mb. Combined forward and reversed subtractions resulted in the identification of 12 clones of human origin, all of which could be confirmed by sequence analysis as originating from the 6q21 region. Expression in human tissues could be confirmed by Northern analysis for two of the clones, one of them showing a high level of expression in stomach tissue.

23
UI - 12079155
AU - Wang CS; Hsieh CC; Chao TC; Jan YY; Jeng LB; Hwang TL; Chen MF; Chen PC;
TI - Chen JS; Hsueh S Resectable gastric cancer: operative mortality and survival analysis.
SO - Chang Gung Med J 2002 Apr;25(4):216-27
AD - Department of General Surgery, Chang Gung Memorial Hospital, Taipei, Taiwan, ROC. wangcs@cgmh.org.tw
BACKGROUND: This study evaluated the survival outcome and determined the prognostic factors for gastric cancer patients who underwent gastric resection in the past 6 years. METHODS: Between 1994 and 2000, a total of 1,322 patients with gastric cancer who underwent gastric resection in our hospital comprised the study subjects. Their mean age was 61.1 (range, 14-92) years. There were 865 male and 457 female patients. Total gastrectomy was performed in 389 (29.4%) and distal gastrectomy in 933 patients. Curative resection was performed in 961, and palliative resection in 361 patients. A D2 or greater lymphadenectomy was required for curative resection. Patients received postoperative chemotherapy if they underwent palliative resection. RESULTS: Early or pT1 gastric cancer accounted for 17.7% and lymph node metastasis for 62.1% of all resected cases. The overall operative mortality and morbidity rates were 3.3% and 18.0%, respectively. The operative mortality for palliative total gastrectomy was particularly high (8.5%). The overall cumulative 5-year survival rate of all resected patients was 45.6%, and it was 57.0% after curative resection. Multivariate analysis revealed that lymph node metastasis, serosal invasion, peritoneal seeding, positive resection margin, liver metastasis, old age, tumor size, and lymphatic invasion were independent prognostic factors. CONCLUSION: The most important prognostic factors for survival were lymph node metastasis, serosal invasion, peritoneal seeding, positive resection margin, liver metastasis, old age, tumor size, and lymphatic invasion. The operative mortality and survival outcome of our gastric cancer patients after gastric resection compared favorably with those of other series in other countries.

24
UI - 11706219
AU - An SK; Han JK; Kim YH; Kim AY; Choi BI; Kim YA; Kim CW
TI - Gastric mucosa-associated lymphoid tissue lymphoma: spectrum of findings at double-contrast gastrointestinal examination with pathologic correlation.
SO - Radiographics 2001 Nov-Dec;21(6):1491-502, discussion 1502-4
AD - Departments of Radiology, Seoul National University College of Medicine, 28 Yongon-dong, Chongno-Gu, Seoul 110-744, Korea.
Mucosa-associated lymphoid tissue (MALT) is found in the surface epithelium of the stomach. MALT lymphoma is extranodal lymphoma originating from MALT. In the stomach, a strong association with Helicobacter pylori infection has been demonstrated. Low-grade gastric MALT lymphoma has been reported to have variable features at upper gastrointestinal (UGI) examination. Twenty-two patients with low-grade MALT lymphoma had ulcers (n = 11), fold thickening (n = 7), mucosal nodularity (n = 7), masses (n = 6), or prominent areae gastricae (n = 4) at UGI examination. Six patients with high-grade MALT lymphoma had masses (n = 4), fold thickening (n = 3), ulcers (n = 1), or mucosal nodularity (n = 1) at UGI examination. These findings were similar to those in gastric carcinoma or gastritis. Differentiation of low-grade MALT lymphoma from gastritis or gastric carcinoma was more difficult than differentiation of high-grade MALT lymphoma. Lesions of MALT lymphoma associated with H pylori gastritis were diffuse or multiple in 65% of cases; however, lesions of MALT lymphoma without proved H pylori gastritis were focal or solitary in 80% of cases. Therefore, multiplicity of lesions in MALT lymphoma was closely associated with H pylori infection.

25
UI - 12065866
AU - Fujimoto T; Zhang B; Minami S; Wang X; Takahashi Y; Mai M
TI - Evaluation of intraoperative intraperitoneal cytology for advanced gastric carcinoma.
SO - Oncology 2002;62(3):201-8
AD - Division of Surgical Oncology, Cancer Research Institute, Kanazawa University, Japan. fuji-cl@gray.plala.or.jp
OBJECTIVE: We evaluated intraperitoneal cytology during surgery as a significant predictor of survival and tried to establish strategies for preventing peritoneal carcinomatosis. METHODS: The study included 236 patients with gastric carcinoma macroscopically invading the serosa who underwent intraperitoneal cytological examination during surgery. In the 215 resected patients, the relationship between cytological positivity for cancer cells and various clinicopathologic features was analyzed. Additionally, postoperative survival was assessed in relation to the positivity of intraoperative cytology. RESULTS: Cancer cells were positive [Cy+] in 78 (33.1%) of 236 patients who underwent cytological examinations. Among 73 patients with peritoneal metastases, 53 patients (72.6%) were Cy+, as were 25 (15.3%) of the 163 patients without peritoneal metastases. Multivariate analysis indicated that peritoneal metastasis (p = 0.0001) and the depth of tumor invasion (p = 0.0069) were significant factors correlated with Cy+. Among patients with curative surgery, the 5-year survival rate of the Cy+ group was 22.2%, which was worse (p = 0.0004) compared with that of the Cy(-) group (60.9%). Among Cy+ patients, the survival rate of the group treated with intraperitoneal administration of mitomycin C (MMC) and OK-432 was better (p = 0.0108) than that of the historical control group. CONCLUSION: These results suggest that intraperitoneal cytological examination can be a significant prognostic factor for gastric carcinoma with serosal invasion. In addition, dissemination of cancer cells in the peritoneum may be controlled by intraperitoneal immunochemotherapy with MMC and OK-432. Copyright 2002 S. Karger AG, Basel

26
UI - 12067995
AU - Clements WM; Wang J; Sarnaik A; Kim OJ; MacDonald J; Fenoglio-Preiser C;
TI - Groden J; Lowy AM beta-Catenin mutation is a frequent cause of Wnt pathway activation in gastric cancer.
SO - Cancer Res 2002 Jun 15;62(12):3503-6
AD - University of Cincinnati Department of Surgery, Division of Surgical Oncology, Ohio 45219, USA.
Studies of Wnt activation in gastric cancer have yielded conflicting results. The goals of this study were to determine the frequency of Wnt pathway activation and beta-catenin mutation in these tumors. Three hundred eleven gastric cancers were examined for beta-catenin expression by immunostaining and dissected using laser capture microscopy to obtain DNA from those tumors with nuclear beta-catenin. Exon 3 of beta-catenin was amplified using PCR and sequenced. Ninety gastric cancers (29%) displayed nuclear beta-catenin. DNAs from 73 tumors were amplified and sequenced; 19 (26%) contained mutations in exon 3 of beta-catenin, whereas no mutations were detected in 19 tumors negative for beta-catenin nuclear staining (P < 0.05). Most mutations were adjacent to or abolished known regulatory phosphorylation sites. Mutations in exon 3 of beta-catenin are common in gastric cancer that display nuclear beta-catenin. These results suggest that Wnt pathway activation contributes to carcinogenesis in a subset of gastric adenocarcinomas.

27
UI - 12115523
AU - Takahashi H; Endo T; Yamashita K; Arimura Y; Yamamoto H; Sasaki S; Itoh
TI - F; Hirata K; Imamura A; Kondo M; Sato T; Imai K Mucin phenotype and microsatellite instability in early multiple gastric cancers.
SO - Int J Cancer 2002 Aug 1;100(4):419-24
AD - First Department of Internal Medicine, Sapporo Medical University, Sapporo, Japan. hiroaki@sapmed.ac.jp
Clinicopathologically, multiple gastric cancers (MGCs) are reported to involve predominantly intestinal-type adenocarcinoma and frequently to be associated with severe intestinal metaplasia. However, there are few reports concerning the characteristic biomarkers of early MGCs. The aim of our study was to identify the cellular lineage defined by mucin phenotypes and the relationships among mucin phenotypes, background mucosa and microsatellite instability (MSI) of early MGCs. We examined mucin phenotypes of 63 surgically resected carcinomas from 25 patients with early MGCs and 39 early solitary gastric cancers (SGCs) by immunohistochemical analysis using a panel of monoclonal antibodies. MSI and the degree of intestinal metaplasia (IM) on the background mucosa were also examined. In early MGCs, the incidence of cancer exhibiting the gastric phenotype (G-type) was 59% (37 of 63 cancers), which was higher than that in early SGCs (23%, 9 of 39 cancers). There was a significant difference between the distributions of mucin phenotypes in early MGCs and early SGCs (p = 0.001). Whereas half of the G-type cancers in early MGCs were related to severe IM, none of the G-type cancers in early SGCs were related to severe IM. In the early MGCs, MSI was observed in 21 of 63 cancers (33.3%). In contrast, MSI was observed in only 3 of the 39 (7.7%) early SGCs, indicating a significant difference between these 2 groups (p < 0.01). Our results suggest that the characteristic features of early MGCs are the gastric mucin dominant phenotype and high frequency of MSI. Copyright 2002 Wiley-Liss, Inc.

28
UI - 12115524
AU - Tsukino H; Kuroda Y; Qiu D; Nakao H; Imai H; Katoh T
TI - Effects of cytochrome P450 (CYP) 2A6 gene deletion and CYP2E1 genotypes on gastric adenocarcinoma.
SO - Int J Cancer 2002 Aug 1;100(4):425-8
AD - Department of Public Health, School of Medicine, Miyazaki Medical College, Miyazaki, Japan.
Cytochrome P450 (CYP) 2A6 and CYP2E1 are enzymes with a high ability to activate a nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), to its potent and ultimate carcinogens. The polymorphic CYP2A6 and CYP2E1 have been implicated in increased susceptibility to certain malignancies. In our study, 120 Japanese patients with gastric adenocarcinoma and 158 healthy controls were compared for frequencies of CYP2A6 and CYP2E1 genotypes. The frequency with which the subjects carried homozygotes of the CYP2A6 gene deletion allele, which causes lack of the enzyme activity, was significantly higher in the gastric cancer patients than in the healthy control subjects (OR = 3.14, 95% confidence interval (95% CI) = 1.05-9.41). Subdividing gastric adenocarcinoma according to tumor differentiation, patients with the well-differentiated type were 4.9-fold more likely to have the CYP2A6 homozygote deletion genotype (OR = 4.91, 95% CI 1.17-20.52). Stratifying by smoking status, we did not find the risk of CYP2A6 gene deletion allele in gastric adenocarcinoma. The CYP2E1 polymorphism detected by RsaI was not significantly different between gastric adenocarcinoma patients (40.8%) and the control population (44.3%). No statistically significant changes were observed when the CYP2E1 genotype was examined relative to tumor differentiation and smoking status. These results suggest that the CTY2A6 deletion is associated with gastric adenocarcinoma among Japanese populations. Copyright 2002 Wiley-Liss, Inc.

29
UI - 10096035
AU - Harris KM; Kelly S; Berry E; Hutton J; Roderick P; Cullingworth J;
TI - Gathercole L; O'Connor PJ; Boyce JC; Smith MA Systematic review of endoscopic ultrasound in gastro-oesophageal cancer.
SO - Health Technol Assess 1998;2(18):i-iv, 1-134
AD - Department of Radiology, Leeds Teaching Hospitals NHS Trust, Leeds General Infirmary, UK.

30
UI - 12101576
AU - Krylov IuV; Malashenko SV; Medvedev MN; Mikhailova EI
TI - [Diagnostic significance of ferritin assay in peritoneal fluid and gastric juice]
SO - Vopr Onkol 2002;48(1):88-90
AD - State Medical University, Vitebsk.
Ferritin was assayed by immunoradiometrical procedure in peritoneal fluid (26 patients with various ovarian pathologies) and gastric juice (18 patients with stomach cancer and 28 cases of gastric ulcer disease). It was found that diagnostic significance of ferritin measurements in peritoneal fluid in ovarian pathology is compromised by inflammation. Therefore, this marker cannot be used to differentiate between malignant and benign ovarian tumor. Single measurements of ferritin for detecting stomach ulcers were also diagnostically irrelevant since the data for stomach cancer and gastric ulcer exacerbation showed no significant difference.

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