We generated gene expression data from the tissues of 50 gastric cancer patients, and applied meta-analysis and gene set analysis to this data and three other stomach cancer gene expression data sets to define the gene expression changes in gastric tumors. By meta-analysis we identified genes consistently changed in gastric carcinomas, while gene set analysis revealed consistently changed biological themes. Genes and gene sets involved in digestion, fatty acid metabolism, and ion transport were consistently down-regulated in gastric carcinomas, while those involved in cellular proliferation, cell cycle, and DNA replication were consistently up-regulated. We also found significant differences between the genes and gene sets expressed in diffuse and intestinal type gastric carcinoma. By gene set analysis of cytogenetic bands, we identified many chromosomal regions with possible gross chromosomal changes (amplifications or deletions). Similar analysis of transcription factor binding sites (TFBSs), revealed transcription factors that may have caused the observed gene expression changes in gastric carcinomas, and we confirmed the overexpression of one of these, E2F1, in many gastric carcinomas by tissue array and immunohistochemistry. We have incorporated the results of our meta- and gene set analyses into a web accessible database (http://human-genome.kribb.re.kr/stomach/).
Purpose: Screening image-enhanced endoscopy for gastrointestinal malignant lesions has progressed. However, the influence of the color enhancement settings for the laser endoscopic system on the visibility of lesions with higher color contrast than their surrounding mucosa has not been established. Materials and Methods: Forty early gastric cancers were retrospectively evaluated using color enhancement settings C1 and C2 for laser endoscopic systems with blue laser imaging (BLI), BLI-bright, and linked color imaging (LCI). The visibilities of the malignant lesions in the stomach with the C1 and C2 color enhancements were scored by expert and non-expert endoscopists and compared, and the color differences between the malignant lesions and the surrounding mucosa were assessed. Results: Early gastric cancers mainly appeared orange-red on LCI and brown on BLI-bright or BLI. The surrounding mucosae were purple on LCI regardless of the color enhancement but brown or pale green with C1 enhancement and dark green with C2 enhancement on BLI-bright or BLI. The mean visibility scores for BLI-bright, BLI, and LCI with C2 enhancement were significantly higher than those with C1 enhancement. The superiority of the C2 enhancement was not demonstrated in the assessments by non-experts, but it was significant for experts using all modes. The C2 color enhancement produced a significantly greater color difference between the malignant lesions and the surrounding mucosa, especially with the use of BLI-bright (P=0.033) and BLI (P<0.001). C2 enhancement tended to be superior regardless of the morphological type, Helicobacter pylori status, or the extension of intestinal metaplasia around the cancer. Conclusions: Appropriate color enhancement settings improve the visibility of malignant lesions in the stomach and color contrast between the malignant lesions and the surrounding mucosa.
Seo, Kyung Won;Jeon, Taeyong;Kim, Sewon;Kim, Sung Soo;Kim, Kwanghee;Suh, Byoung-Jo;Hwang, Sunhwi;Choi, SeongHee;Ryu, Seungwan;Min, Jae Seok;Lee, Young-Joon;Jee, Ye Seob;Chae, Hyeondong;Yang, Doo Hyun;Lee, Sang Ho
Journal of Gastric Cancer
/
v.17
no.1
/
pp.52-62
/
2017
Purpose: The Trastuzumab for gastric cancer (GC) trial identified human epidermal growth factor receptor 2 (HER2) as a predictor of successful treatment with trastuzumab (HER2 receptor targeting agent) among patients with advanced/metastatic GC. To date, the prevalence of HER2 overexpression in the Korean population is unknown. The present study aimed to assess the incidence of HER2 positivity among GC and gastroesophageal (GE) junction cancer samples and the relationship between HER2 overexpression and clinicopathological characteristics in Korean patients. Materials and Methods: Tumor samples collected from 1,695 patients with histologically proven GC or GE junction enrolled at 14 different hospitals in Korea were examined. After gathering clinicopathological data of all patients, HER2 status was assessed by immunohistochemistry (IHC) at each hospital, and IHC 2+ cases were subjected to silver-enhanced in situ hybridization at 3 central laboratories. Results: A total of 182 specimens tested positive for HER2, whereas 1,505 tested negative. Therefore, the overall HER2-positive rate in this study was 10.8% (95% confidence interval=9.3%-12.3%). The HER2-positive rate was higher among intestinal-type cases (17.6%) than among other types, and was higher among patients older than 70 years and 50 years of age, compared to other age groups. Conclusions: Our evaluation of the HER2 positivity rate (10.8%) among Korean patients with GC and GE junction indicated the necessity of epidemiological data when conducting studies related to HER2 expression in GC and GE junction.
Purpose: The adipocyte-derived cytokine leptin plays a major role in the control of stable body weight by suppressing food intake and increasing energy metabolism. Leptin regulates the cell proliferation of various epithelial cells and it may be involved in the promotion of cancer. Leptin and its receptor are highly expressed in gastric adenocarcinoma, but the association between the serum leptin level and the tissue expression of leptin is uncertain. We evaluated the serum leptin level and the expressions of leptin and leptin receptor in gastric cancer, and we explore the possible mechanism and role of leptin in the carcinogenesis of gastric cancer. Materials and Methods: 72 carcinomas that were curatively resected at our hospital from October 2005 to March 2007 were included in this study. By immunoassay and immunohistochemical staining, we evaluated the serum leptin level and the expressions of leptin and its receptor, and we analyzed their relationship together with the clinicopathological variables. Results: The serum leptin level was increased as the patient's BMI increased and it was decreased in H. pylori infected patients. The expression of leptin was increased as the TNM stage increased (P=0.014), and the expression of leptin receptor in the intestinal type gastric adenocarcinoma was higher than that in the diffuse type gastric adenocarcinoma (71.4% vs 28.6%, respectively, P=0.033). Conclusion: There was no significant correlation between the serum leptin level and expression of leptin in gastric cancer patients. The expression of leptin was associated with the TNM stage, but its role in the pathogenesis of gastric cancer has to be elucidated.
Purpose: Transcriptional factors of CREB (cAMP response element binding protein) are involved in regulating the gene expression in response to a variety of signaling pathways. The proteins produced by the CREB genes play key roles in many physiological processes, including memory and long-term potentiation. The retinoic acid receptor (RAR) axis mediates epithelial cell differentiation and proliferation in many tissues. This study examined the expressions of RAR and CREB and their relationship with the clinicopathologic factors and their significance. Materials and Methods: The levels of the RAR and CREB expressions were measured in 150 gastric adenocarcinomas by performing immunohistochemical staining. Results: 1. An RAR protein expression was found in 63.3% of the adenocarcinomas (95/150) and a CREB expression was found in 60.7% (91/150) of the adenocarcinomas. 2. An RAR protein expression was found in 72.2% (78/108) of the intestinal type adenocarcinomas and in 40.5% (17/42) of the diffuse type adenocarcinomas (P<0.05). Based on the depth of invasion, an RAR protein expression was found in 58.3% (14/24) of the T1 adenocarcinomas, in 61.9% (13/21) of the T2 adenocarcinomas, in 63.5% (61/96) of the T3 adenocarcinomas, in 77.8% (7/9) of the T4 adenocarcinomas and in 74.7% (62/83) of the adenocarcinomas with lymph node metastasis and in 49.2% (33/67) of the adenocarcinomas without lymph node metastasis (P<0.01). 3. A CREB expression was found in 69.4% (75/108) of the intestinal type and in 38.1% (16/42) of the diffuse type (P>0.05). Based on the depth of invasion, a CREB expression was found in 50% (12/24) of the T1 adenocarcinomas, in 52.4% (11/21) of the T2 adenocarcinomas, in 64.6% (62/96) of the T3 adenocarcinomas, in 66.6% (6/9) of the T4 adenocarcinomas, in 71.1% (59/83) of the adenocarcinomas with lymph node metastasis and in 47.8% (32/67) of the adenocarcinomas without lymph node metastasis (P<0.01). 4. The RAR protein and CREB expressions coincided in 71.4% of the gastric adenocarcinomas and a significant correlation between them was found (P<0.05). Conclusion: We found a significant relationship between the expression of RAR and CREB and the histology and lymph node metastasis of gastric cancer. Further studies are needed to confirm their biologic meaning in gastric carcinogenesis.
Jung, Da Hyun;Kim, Jie-Hyun;Lee, Yong Chan;Lee, Sang Kil;Shin, Sung Kwan;Park, Jun Chul;Chung, Hyun Soo;Kim, Hyunki;Kim, Hoguen;Kim, Yong Hoon;Park, Jae Jun;Youn, Young Hoon;Park, Hyojin
Journal of Gastric Cancer
/
v.15
no.4
/
pp.246-255
/
2015
Purpose: The importance of Helicobacter pylori eradication after endoscopic resection (ER) of gastric neoplasms remains controversial. In this study, we clarified the importance of H. pylori eradication for metachronous lesions after ER. Materials and Methods: This study included 3,882 patients with gastric neoplasms who underwent ER. We included patients infected with H. pylori who received eradication therapy. Among them, 34 patients with metachronous lesions after ER and 102 age- and sex-matched patients (nonmetachronous group) were enrolled. Background mucosal pathologies such as atrophy and intestinal metaplasia (IM) were evaluated endoscopically. The expression levels of CDX1, CDX2, Sonic hedgehog (SHH), and SOX2 were evaluated based on H. pylori eradication and the development of metachronous lesions. Results: The eradication failure rate was higher in the metachronous group than in the nonmetachronous group (P=0.036). Open-type atrophy (P=0.003) and moderate-to-severe IM (P=0.001) occurred more frequently in the metachronous group. In patients with an initial diagnosis of dysplasia, the eradication failure rate was higher in the metachronous group than in the nonmetachronous group (P=0.002). In addition, open-type atrophy was more frequent in the metachronous group (P=0.047). In patients with an initial diagnosis of carcinoma, moderate-to-severe IM occurred more frequently in the metachronous group (P=0.003); however, the eradication failure rate was not significantly different between the two groups. SHH and SOX2 expression was increased, and CDX2 expression was decreased in the nonmetachronous group after eradication (P<0.05). Conclusions: Open-type atrophy, moderate-to-severe IM, and H. pylori eradication failure were significantly associated with metachronous lesions. However, eradication failure was significantly associated with dysplasia, but not carcinoma, in the metachronous group. Thus, H. pylori eradication may play an important role in preventing metachronous lesions after ER for precancerous lesions before carcinomatous transformation.
Kim, Min Kuk;An, Ji Yeong;Choi, Min Gew;Noh, Jae Hyung;Sohn, Tae Sung;Kim, Sung
Journal of Gastric Cancer
/
v.8
no.3
/
pp.136-140
/
2008
Purpose: Stage IV early gastric carcinoma (EGC) is a rare disease. We report here on 10 cases of EGC that showed metastasis in more than 15 lymph nodes. Materials and Methods: A total of 8354 cases of gastric carcinoma in patients who underwent surgical procedures between January 2001 and January 2007 at Samsung Medical Center were studied, and 10 cases were classified as stage IV EGC. We investigated their clinicopathologic characteristics. Results: There were 5 males and 5 females. Their ages at operation ranged from 46 to 76 years with a mean age of 61. All of the 10 patients had undergone curative resection for gastric cancer. The pathological diagnosis confirmed that all of the patients had tumor confined to the submucosa. The median size of the tumors was 5.3cm and the mean number of dissected nodes was 45.5 with a mean number of 22.2 involved nodes. Six cases were classified as the diffuse type and 4 were classified as the intestinal type by Lauren's classification. Histologically, 3 cases were signet ring cell carcinoma, 3 were poorly differentiated, 2 were moderately differentiated and 2 were well differentiated adenocarcinoma. Endolymphatic invasion was found in 9 cases. The median follow-up was 31 months. Adjuvant chemotherapy was done in 9 patients, and the patient who did not receive chemotherapy died by cerebrovascular accident. 2 patient had recurrence of gastric cancer and 7 survived without recurrence. Conclusion: More cases should be collected and further studies on the molecular and cellular tumor characteristics are required to characterize these tumors that show aggressive lymphatic spread.
Purpose: Recently, the use of laparoscopic assisted gastrectomy for early gastric cancer has been on the increase and the procedure has been quickly adopted by clincians. However, there are few reports regarding the safety and risk of this type of surgery. The aim of this study is to evaluate the morbidity and to verify the safety of laparoscopic assisted gastrectomy for early gastric cancer. Materials and Methods: A total of 376 patients that had undergone laparoscopic assisted gastrectomy for early gastric cancer between April 2004 and December 2006 were reviewed retrospectively. The clinicopathological characteristics, operative complications, and factors related to complications were evaluated. Results: The overall operative morbidity and mortality rates were 10.6% and 0%, intraoperative morbidity was 1.1% (4 of 376 patients) and post operative morbidity was 9.6% (36 of 376 patients). Most complications required no surgery except for an intestinal obstruction in two cases. Multivariate analysis of risk factors related to operative morbidity determined that age was an independent factor associated with morbidity (P=0.021). Conclusion: The complication rate of laparoscopic assisted gastrectomy is low and most complications can be managed by conservative methods rather than with surgery. There were no specific predicting factors for complications except old age. Laparoscopy is a technically feasible and acceptable surgical modality for early gastric cancer.
Buyukasik, Kenan;Sevinc, Mert Mahsuni;Gunduz, Umut Riza;Ari, Aziz;Gurbulak, Bunyamin;Toros, Ahmet Burak;Bektas, Hasan
Asian Pacific Journal of Cancer Prevention
/
v.16
no.7
/
pp.2999-3001
/
2015
Background: This study aimed to evaluate upper gastrointestinal polyps detected during esophago-gastroduodenoscopy tests. Materials and Methods: We conducted a retrospective analysis on data regarding 55,987 upper gastrointestinal endoscopy tests performed at the endoscopy unit of Istanbul Education and Research Hospital between January 2006 and June 2012. Results: A total of 66 upper gastrointestinal polyps from 59 patients were analyzed. The most common clinical symptom was dyspepsia, observed in 41 cases (69.5%). The localizations of the polyps were as follows: 29 in the antrum (43.9%), 15 in the corpus (22.7%), 11 in the cardia (16.7%), 3 in the fundus (4.54%), 3 in the second portion of the duodenum (4.54%), 2 in the bulbus (3.03%) and 3 in the lower end of the esophagus (4.54%). Histopathological types of polyps included hyperplastic polyps (44) (66.7%), faveolar hyperplasia (8) (12.1%), fundic gland polyps (4) (6.06%), squamous cell polyps (4) (6.06%), hamartomatous polyps (3) (4.54%), and pyloric gland adenoma (3) (4.54%). Histopathological analysis of the gastric mucosa showed chronic atrophic gastritis in 30 cases (50.84%), HP infection in 33 cases (55.9%) and intestinal metaplasia in 19 cases (32.20%). In 3 cases with multiple polyps, adenocarcinoma was detected in hyperplastic polyps. Conclusions: Among polypoid lesions of the upper gastrointestinal tract, the most common histological type is hyperplastic polyps. Generally, HP infection is associated with chronic atrophic gastritis and intestinal metaplasia. The incidence of adenocarcinoma tends to be higher in patients with multiple hyperplastic polyps.
Journal of the Korean Society of Food Science and Nutrition
/
v.33
no.5
/
pp.791-796
/
2004
This study was peformed to screen the biological activities of Pleurotus ferulea (K5 and K8 strains). The cap of K5 strain is well developed than stalk, and vice versa in K8. The ethanol extract of Pleurotus ferulea exhibited significant free radical scavenging activity (35∼36%), suggesting possible effect on many degenerative diseases originated from the reaction of oxygen species. Acetylcholinesterase inhibitor is proven to be the most effective factor for Alzheimer disease induction, and ethanol extract of Pleurotus ferulea significantly inhibited acetylcholinesterase activity (25∼35%) in uitro. Moreover, ethanol extract of Pleurotus ferulea suppressed liver fibrosis by 3∼12% in uitro. However, Pleurotus ferulea feruled to inhibit glucose uptake in human intestinal cell line. Viability of gastric and colon cancer cells was also not affected by Pleurotus ferulea extract. In conclusion Pleurotus ferulea exhibited significant effect on free radical scavenging, acetylcholinesterase inhibiton and brain cell protection. However, Pleurotus ferulea failed to affect glucose uptake, and cytotoxicity of gastric and cancer cells. In general, K8 revealed more significant effects than K5.
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