Gastric adenocarcinoma in a diamond python (Morelia spilota spilota).

Science.gov (United States)

Baron, H R; Allavena, R; Melville, L M; Doneley, R J T

2014-10-01

A 5-year-old captive male diamond python (Morelia spilota spilota) was presented with a 1-month history of regurgitation and anorexia and discrete coelomic distention. Physical examination revealed a firm, immobile mass at approximately two-thirds of the snout-vent length from the front of the head. Ultrasound-guided fine needle aspirate biopsy of the mass in the region of the stomach showed necrosis with bacterial infiltration and possibly neoplastic changes. A gastroscopy was conducted, but showed grossly normal gastric mucosa, confirmed by biopsy. On exploratory coeliotomy, it was confirmed the mass involved most of the stomach wall and occluded the gastric lumen. The mass was completely excised and based on histopathology, a diagnosis of gastric adenocarcinoma was made. The snake was found dead 12 h postoperatively, but no specific cause of death was found on postmortem examination. Most cases of adenocarcinoma in snakes go undiagnosed. This case report illustrates that the architecture of gastric masses may lead to false-negative gastric biopsy results in snakes with neoplasia. © 2014 Australian Veterinary Association.

Soluble Fas might serve as a diagnostic tool for gastric adenocarcinoma

International Nuclear Information System (INIS)

Boroumand-Noughabi, Samaneh; Mashhadinejad, Mojtaba; Tavakkol-Afshari, Jalil; Sima, Hamid Reza; Ghaffarzadehgan, Kamran; Jafarzadeh, Mostafa; Raziee, Hamid Reza; Hosseinnezhad, Hanieh; Moaven, Omeed; Rajabi-Mashhadi, Mohammad Taghi; Azarian, Amir Abbas

2010-01-01

Fas (Apo-1/CD95) and its specific ligand (FasL) are key elements in apoptosis. They have been studied in different malignancies but there are few published studies about the soluble forms of these markers (i.e. sFas/sFasL) in gastric cancer. We have compared the serum levels of sFas/sFasL in gastric adenocarcinoma patients and cases with pre-neoplastic lesions as potential markers for early diagnosis, and investigated their relation with clinicopathological characteristics. Fifty-nine newly-diagnosed cases of gastric adenocarcinoma who had undergone gastrectomy, along with 62 endoscopically- and histologically-confirmed non-cancer individuals were enrolled in this study. sFas/sFasL serum levels were detected by Enzyme Linked Immunosurbent Assay. Mean serum sFas level was significantly higher in gastric cancer patients than in control group (305.97 ± 63.71 (pg/ml) vs. 92.98 ± 4.95 (pg/ml), P < 0.001); while the mean serum level of sFasL was lower in patients with gastric adenocarcinoma (0.138 ± 0.04 (pg/ml) vs. 0.150 ± 0.02 (pg/ml), P < 0.001). Mean serum levels of sFas/sFasL were significantly different in both intestinal/diffuse and cardiac/non-cardiac subtypes when compared to the control group (P < 0.001). There was an increase in the serum level of sFas from the first steps of pre-neoplastic lesions to gastric adenocarcinoma (P < 0.001). Patients who had no lymph node involvement (N 0 ) showed significantly higher serum levels of sFas compared to others (P = 0.044). Production of sFas may play a critical role in the carcinogenesis of intestinal-type gastric cancer. sFas serum level may serve as a non-invasive tool for early diagnosis of gastric cancer

Gastric candidiasis with gastric adenocarcinoma intestinal type: A rare association

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Kalaivani Selvi Subramanian

2015-01-01

Full Text Available Candidiasis of the gastrointestinal tract most commonly involves the esophagus and rarely involves the stomach and small bowel. The association of gastric carcinoma with candidiasis is even rare and only a very few case reports are available. We present here a 40-year-old female who presented with complaints of gastric outlet obstruction who on endoscopy showed a malignant ulcer involving the lesser curvature. The histopathological examination of biopsy from the ulcer showed adenocarcinoma intestinal type along with yeast and pseudohyphae forms of candida species.

Expression and Significance of Cyclophilin J in Primary Gastric Adenocarcinoma.

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Gong, Zhaohua; Mu, Yuling; Chen, Jian; Chu, Hongjin; Lian, Peiwen; Wang, Congcong; Wang, Jiahui; Jiang, Lixin

2017-08-01

Biomarkers are essential in early diagnosis and understanding of the molecular mechanism of human cancer. The expression of cyclophilin J, a novel member of the cyclophilin family, was investigated in primary gastric adenocarcinoma. Western blot analysis was carried out on 36 paired tumor and normal tissue samples; immunohistochemical analysis was carried out on 120 gastric carcinoma tissues and normal adjacent tissue. Cyclophilin J protein was overexpressed in 72.2% of gastric carcinoma tissues compared to adjacent normal tissues. Immunohistochemical analysis revealed that cyclophilin J was overexpressed in 49.2% (59/120) and 23.3% (28/120) of gastric carcinoma tissues and adjacent tissues, respectively (pJ was associated with the degree of differentiation, but not with lymph node metastasis, gender or depth of tumor infiltration. The overall survival of patients showed no association with the overexpression of cyclophilin J protein. Cyclophilin J expression was up-regulated in gastric carcinoma compared to normal gastric tissues. However, in order to confirm its association with the survival of patients with gastric cancer, more cases need to be studied. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

C5b-9 Staining Correlates With Clinical and Tumor Stage in Gastric Adenocarcinoma.

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Chen, Jian; Yang, Wei-Jun; Sun, Hai-Jian; Yang, Xia; Wu, Yu-Zhang

2016-08-01

The complement system is a critical part of the immune response, acting in defense against viral infections, clearance of immune complexes, and maintenance of tissue homeostasis. Upregulated expression of the terminal complement complex, C5b-9, has been observed on various tumor cells, such as stomach carcinoma cells, and on cells in the necrotic regions of these tumors as well; however, whether and how C5b-9 is related to gastric cancer progression and severity remains unknown. In this study, human gastric adenocarcinoma (HGAC) tissues (n=47 cases) and patient-matched adjacent nontumoral parenchyma (n=20 cases) were evaluated by tissue microarray and immunohistochemistry. The HGAC tissues showed upregulated C5b-9 expression. Multinomial logistic regression and likelihood ratio testing showed that overexpression of C5b-9 in HGAC tissue was significantly correlated with clinical stage (P=0.007) and tumor stage (P=0.005), but not with tumor distant organ metastasis, lymphoid nodal status, sex, or age. Patients with late-stage gastric adenocarcinoma had a higher amount of tumor cells showing positive staining for C5b-9 than patients with early-stage disease. These results may help in diagnosis and assessment of disease severity of human gastric carcinoma.

Magnetic resonance imaging findings and prognosis of gastric-type mucinous adenocarcinoma (minimal deviation adenocarcinoma or adenoma malignum) of the uterine corpus: Two case reports

OpenAIRE

HINO, MAYO; YAMAGUCHI, KEN; ABIKO, KAORU; YOSHIOKA, YUMIKO; HAMANISHI, JUNZO; KONDOH, EIJI; KOSHIYAMA, MASAFUMI; BABA, TSUKASA; MATSUMURA, NORIOMI; MINAMIGUCHI, SACHIKO; KIDO, AKI; KONISHI, IKUO

2016-01-01

Our group previously documented the first, very rare case of primary gastric-type mucinous adenocarcinoma of the uterine corpus. Although this type of endometrial cancer appears to be similar to the gastric-type adenocarcinoma of the uterine cervix, its main symptoms, appearance on magnetic resonance imaging (MRI) and prognosis have not been fully elucidated due to its rarity. We herein describe an additional case of gastric-type mucinous adenocarcinoma of the endometrium and review the relev...

Composite protective lifestyle factors and risk of developing gastric adenocarcinoma: the Singapore Chinese Health Study.

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Wang, Zhensheng; Koh, Woon-Puay; Jin, Aizhen; Wang, Renwei; Yuan, Jian-Min

2017-02-28

Incidence of gastric cancer is the highest in Eastern Asia. Multiple modifiable lifestyle factors have been identified as risk factors for gastric cancer. However, their aggregated effect on the risk of gastric cancer has not been examined among populations with high prevalence of Helicobacter pylori. A study was conducted to examine the association between multiple lifestyle factors together and the risk of developing gastric adenocarcinoma in the Singapore Chinese Health Study, a prospective cohort of 63 257 men and women between 45 and 74 years enroled during 1993-1998. Composite score of cigarette smoking, alcohol consumption, obesity, dietary pattern, and sodium intake at baseline was assessed with hazard ratio (HR) and 95% confidence interval (CI) of gastric adenocarcinoma using Cox regression method. Higher healthy composite lifestyle scores were significantly associated with reduced risk of gastric adenocarcinoma in a dose-dependent manner. Hazard ratios (95% CIs) for total, cardia, and non-cardia gastric adenocarcinoma for the highest (score 5) vs lowest composite score (score 0/1/2) were 0.42 (0.31-0.57), 0.22 (0.10-0.47), and 0.55 (0.39-0.78), respectively (all P trend <0.001). These lifestyles together accounted for 48% of total gastric adenocarcinoma cases in the study population. The inverse association was observed in both genders, and remained after exclusion of first 5 years of follow-up. The inverse association between the aggregated healthy lifestyle factors and the risk of gastric adenocarcinoma is in dose-dependent manner in this highly H. pylori-exposed population. These lifestyle factors together may account for up to half of disease burden in this study population.

Helical CT findings of gastric wall thickening by peptic ulcer : compared with gastric adenocarcinoma with ulcer

International Nuclear Information System (INIS)

Jung, Won Jung; Choi, Jong Chul; Seo, Keum Soo; Koo, Bon Sik; Park, Byeong Ho; Kim, Chung Ku; Lee, Ki Nam; Nam, Kyung Jin

2000-01-01

To compare on the basis of helical CT findings gastric wall thickening of peptic gastric ulcer with that of gastric adenocarcinoma with ulcer. Thirty-eight patients with pathologically proven gastric lesion (17 cases of peptic ulcer and 21 cases of ulcerative or ulceroinfiltrative gastric cancer (Borrman type II, III) underwent helical CT, and the findings were retrospectively reviewed in terms of maximum abnormal wall thickness, preservation of the inner enhancing layer, the presence three discriminate layers of gastric wall, and enhancement pattern. The enhancement pattern of abnormally thick wall was compared with that of the portal phase of back muscle, and was defined as low, iso, or high. The Chi-square test and Student t test were used for statistical analysis. In cases of peptic ulcer and gastric cancer with ulceration, maximum abnormal wall thickness was 7-30 (mean, 16.1)mm, and 11-33 (mean, 21.8)mm, respectively. The inner enhancing layer was preserved in 15 of 17 patients (88.2%) and one of 21 (4.8%); three discriminate layers of gastric wall were observed in 8 of 17 patients (47.0%), and one of 21 (4.8%). The enhancement pattern was low in 12 of 17 patients (70.5%), and 3 of 21 (14.3%); iso in 4 of 17 (23.5%), and 4 of 21 (19.0%), and high in one of 17 (5.9%), and 14 of 21 (66.7%). All figures refer, respectively, to the two distinct conditions. In terms of preservation of the inner enhancing layer, three discriminate layers of gastric wall, and a low enhancement pattern, there were statistically significant differences between peptic ulcer and gastric adenocarcinoma with ulcer. Where the enhancement was high, however, the statistically significant difference between the two conditions was even greater. There was no statistically significant difference in terms of gastric wall thickness or iso-attenuation of thickened gastric. Helical CT findings of gastric wall thickening, preservation of the inner enhancing layer, and three discriminate layers of

Helical CT findings of gastric wall thickening by peptic ulcer : compared with gastric adenocarcinoma with ulcer

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Jung, Won Jung; Choi, Jong Chul; Seo, Keum Soo; Koo, Bon Sik; Park, Byeong Ho; Kim, Chung Ku; Lee, Ki Nam; Nam, Kyung Jin [College of Medicine, Dong A University, Pusan (Korea, Republic of)

2000-02-01

To compare on the basis of helical CT findings gastric wall thickening of peptic gastric ulcer with that of gastric adenocarcinoma with ulcer. Thirty-eight patients with pathologically proven gastric lesion (17 cases of peptic ulcer and 21 cases of ulcerative or ulceroinfiltrative gastric cancer (Borrman type II, III)) underwent helical CT, and the findings were retrospectively reviewed in terms of maximum abnormal wall thickness, preservation of the inner enhancing layer, the presence three discriminate layers of gastric wall, and enhancement pattern. The enhancement pattern of abnormally thick wall was compared with that of the portal phase of back muscle, and was defined as low, iso, or high. The Chi-square test and Student t test were used for statistical analysis. In cases of peptic ulcer and gastric cancer with ulceration, maximum abnormal wall thickness was 7-30 (mean, 16.1)mm, and 11-33 (mean, 21.8)mm, respectively. The inner enhancing layer was preserved in 15 of 17 patients (88.2%) and one of 21 (4.8%); three discriminate layers of gastric wall were observed in 8 of 17 patients (47.0%), and one of 21 (4.8%). The enhancement pattern was low in 12 of 17 patients (70.5%), and 3 of 21 (14.3%); iso in 4 of 17 (23.5%), and 4 of 21 (19.0%), and high in one of 17 (5.9%), and 14 of 21 (66.7%). All figures refer, respectively, to the two distinct conditions. In terms of preservation of the inner enhancing layer, three discriminate layers of gastric wall, and a low enhancement pattern, there were statistically significant differences between peptic ulcer and gastric adenocarcinoma with ulcer. Where the enhancement was high, however, the statistically significant difference between the two conditions was even greater. There was no statistically significant difference in terms of gastric wall thickness or iso-attenuation of thickened gastric. Helical CT findings of gastric wall thickening, preservation of the inner enhancing layer, and three discriminate layers of

UCH-LI acts as a novel prognostic biomarker in gastric cardiac adenocarcinoma.

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Yang, Honghong; Zhang, Chunhong; Fang, Shan; Ou, Rongying; Li, Wenfeng; Xu, Yunsheng

2015-01-01

Gastric cardiac adenocarcinoma (GCA) accounts for a majority of gastric cancer population and harbors unfavorable outcome. Ubiquitin C-terminal hydrolase L1 (UCH-L1) belongs to the deubiquitinating enzyme family, which could regulate cell growth in human cancers. In the present study, expression of UCH-L1 was evaluated in 196 GCAs by immunohistochemistry using tissue microarray and its function on gastric cancer cells was measured. UCH-L1 expression was increased in GCA specimens, compared with their normal tissues and UCH-L1 overexpression is tightly correlated with tumor size and overall TNM stage. Log-rank analysis showed that UCH-L1 positive is reversely associated with cumulative survival (Pstage that is a known negative factor in gastric cancers (Hazard Ratio=0.33, Pgastric cancer cells. Our findings suggest that UCH-L1 is a promising prognostic biomarker for GCAs and might play an important role in the carcinogenesis of gastric cancer.

Application of the standard lymphadenectomy in gastric adenocarcinoma

International Nuclear Information System (INIS)

Aguirre Fernandez, Roberto Eduardo; LLera Dominguez, Gerardo de la; Pennon Guerra, Maria; Alvarez Perez, Alvaro

2011-01-01

The 5-years postoperative survival of 132 patients operated on due to gastric adenocarcinoma that underwent lymphadenectomy of the two first ganglionic levels. The results of the epidemiological parameters were determined and the survival by Kaplan-Meier method was defined

Inducible nitric oxide synthase, nitrotyrosine and apoptosis in gastric adenocarcinomas and their correlation with a poor survival

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Li, Long-Gang; Xu, Hui-Mian

2005-01-01

AIM: To detect the presence of inducible nitric oxide synthase (iNOS), nitrotyrosine (NT) and apoptosis in gastric adenocarcinomas and their possible correlations with the clinicopathological characteristics and prognosis of gastric adenocarcinoma. METHODS: Sixty-six specimens of gastric adenocarcinoma and corresponding adjacent normal gastric tissues were studied. Immunohistochemistry was employed to localize iNOS and NT protein and an immunohistochemical scoring system was used. The occurrence of apoptotic cell death (apoptotic index [AI]) was analyzed by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate biotin nick-end labeling (TUNEL) method. RESULTS: Results showed that iNOS expression was detected at an intermediate or high level in 41 of 66 (62%) specimens of gastric adenocarcinoma. NT expression was 58%. Neither of them was found in the normal gastric tissues; there were significant positive correlations among iNOS expression, NT expression and AI. Many clinicopathologic characteristics of gastric adenocarcinoma, such as tumor size, depth of invasion, lymph node metastasis and TNM staging, were related to iNOS and NT expressions (P<0.05). In 66 surviving patients, the 5-year survival rate of 41 patients who had tumors with intermediate or high iNOS expressions and high AIs (4.09%; 19.96%) was significantly lower than that of 25 patients who had tumors with negative or low iNOS expressions and low AIs (0.79%; 47.14%) (P = 0.001). COX’s multivariate analysis revealed that the iNOS expression was identified as one of the significant independent prognostic factors predictive of a poor survival (relative risk [RR] = 2.69). CONCLUSION: NO produced by iNOS may play a stronger role in promoting gastric adenocarcinoma growth than in suppressing its growth. iNOS and NT expressions by gastric adenocarcinoma may correlate with a poor survival. PMID:15849807

Inhibitory effects of CP on the growth of human gastric adenocarcinoma BGC-823 tumours in nude mice.

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Wang, Hai-Jun; Liu, Yu; Zhou, Bao-Jun; Zhang, Zhan-Xue; Li, Ai-Ying; An, Ran; Yue, Bin; Fan, Li-Qiao; Li, Yong

2018-05-01

Objective To investigate the potential antitumour effects of [2-(6-amino-purine-9-yl)-1-hydroxy-phosphine acyl ethyl] phosphonic acid (CP) against gastric adenocarcinoma. Methods Human BGC-823 xenotransplants were established in nude mice. Animals were randomly divided into control and CP groups, which were administered NaHCO 3 vehicle alone or CP dissolved in NaHCO 3 (200 µg/kg body weight) daily, respectively. Tumour volume was measured weekly for 6 weeks. Resected tumours were assayed for proliferative activity with anti-Ki-67 or anti-proliferating cell nuclear antigen (PCNA) antibodies. Cell apoptosis was examined using terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) assays and with caspase-3 immunostaining. Proteins were measured by Western blotting. Results There was a significant reduction in tumour volume and a reduced percentage of Ki-67-positive or PCNA-positive cells in the CP group compared with the control group. The percentage of TUNEL-positive or caspase 3-positive cells significantly increased following CP treatment compared with the control group. Tumours from the CP group had higher levels of phosphorylated-extracellular signal-regulated kinase (p-ERK) and phosphorylated-AKT (p-AKT) compared with control tumours. Conclusion CP treatment inhibited tumour growth and induced tumour cell apoptosis in a nude mouse model of BGC-823 gastric adenocarcinoma. Activation of the AKT and ERK signalling pathways may mediate this antitumour activity.

Effect of radiation on the expression of carcinoembryonic antigen of human gastric adenocarcinoma cells

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Hareyama, M.; Imai, K.; Kubo, K.; Takahashi, H.; Koshiba, H.; Hinoda, Y.; Shidou, M.; Oouchi, A.; Yachi, A.; Morita, K. (Sapporo Medical College (Japan))

1991-05-01

The changes of antigenic expression of cultured human gastric adenocarcinoma MKN45 cells caused by irradiation were investigated to elucidate the immune responses to localized irradiation. The expression of carcinoembryonic antigen (CEA) showed remarkable increases in the culture supernatant and on the surface of the membrane of irradiated cells. The expression of major histocompatibility complex Class I antigen on the membrane also was enhanced by irradiation. In addition, the irradiated cell groups, when analyzed using a CEA-specific probe, showed remarkable increases in the CEA mRNA. These enhancements increased in the 10-Gy and 15-Gy irradiated populations compared with the 5-Gy irradiated population. These results suggest that the enhancement of expression of CEA by radiation takes place at the CEA gene expression (mRNA) level but not at the protein level.

Prognostic significance of tumor budding and single cell invasion in gastric adenocarcinoma

Directory of Open Access Journals (Sweden)

Che K

2017-02-01

Full Text Available Keying Che,1,* Yang Zhao,2,3,* Xiao Qu,1 Zhaofei Pang,1 Yang Ni,4 Tiehong Zhang,4 Jiajun Du,1,5 Hongchang Shen4 1Institute of Oncology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, 2Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Collaborative Innovation Center of Cancer Medicine, Fudan University Shanghai Cancer Center, 3Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 4Department of Oncology, Shandong Provincial Hospital Affiliated to Shandong University, 5Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, People’s Republic of China *These authors contributed equally to this work Purpose: Gastric carcinoma (GC is a highly aggressive cancer and one of the leading causes of cancer-related deaths worldwide. Histopathological evaluation pertaining to invasiveness is likely to provide additional information in relation to patient outcome. In this study, we aimed to evaluate the prognostic significance of tumor budding and single cell invasion in gastric adenocarcinoma.Materials and methods: Hematoxylin and eosin-stained slides generated from 296 gastric adenocarcinoma patients with full clinical and pathological and follow-up information were systematically reviewed. The patients were grouped on the basis of tumor budding, single cell invasion, large cell invasion, mitotic count, and fibrosis. The association between histopathological parameters, different classification systems, and overall survival (OS was statistically analyzed.Results: Among the 296 cases that were analyzed, high-grade tumor budding was observed in 49.0% (145 of them. Single cell invasion and large cell invasion were observed in 62.8% (186 and 16.9% (50 of the cases, respectively. Following univariate analysis, patients with high-grade tumor budding had shorter OS than those with low-grade tumor budding (hazard ratio [HR]: 2.260, P<0

Role of Rac1 Pathway in Epithelial-to-Mesenchymal Transition and Cancer Stem-like Cell Phenotypes in Gastric Adenocarcinoma.

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Yoon, Changhwan; Cho, Soo-Jeong; Chang, Kevin K; Park, Do Joong; Ryeom, Sandra W; Yoon, Sam S

2017-08-01

Rac1, a Rho GTPase family member, is dysregulated in a variety of tumor types including gastric adenocarcinoma, but little is known about its role in cancer stem-like cells (CSCs). Therefore, Rac1 activity and inhibition were examined in gastric adenocarcinoma cells and mouse xenograft models for epithelial-to-mesenchymal transition (EMT) and CSC phenotypes. Rac1 activity was significantly higher in spheroid-forming or CD44 + gastric adenocarcinoma CSCs compared with unselected cells. Rac1 inhibition using Rac1 shRNA or a Rac1 inhibitor (NSC23766) decreased expression of the self-renewal transcription factor, Sox-2, decreased spheroid formation by 78%-81%, and prevented tumor initiation in immunodeficient mice. Gastric adenocarcinoma CSCs had increased expression of the EMT transcription factor Slug, 4.4- to 8.3-fold greater migration, and 4.2- to 12.6-fold greater invasion than unselected cells, and these increases could be blocked completely with Rac1 inhibition. Gastric adenocarcinoma spheroid cells were resistant to 5-fluorouracil and cisplatin chemotherapy, and this chemotherapy resistance could be reversed with Rac1 shRNA or NSC23766. The PI3K/Akt pathway may be upstream of Rac1, and JNK may be downstream of Rac1. In the MKN-45 xenograft model, cisplatin inhibited tumor growth by 50%, Rac1 inhibition by 35%, and the combination by 77%. Higher Rac1 activity, in clinical specimens from gastric adenocarcinoma patients who underwent potentially curative surgery, correlated with significantly worse survival ( P = 0.017). In conclusion, Rac1 promotes the EMT program in gastric adenocarcinoma and the acquisition of a CSC state. Rac1 inhibition in gastric adenocarcinoma cells blocks EMT and CSC phenotypes, and thus may prevent metastasis and augment chemotherapy. Implications: In gastric adenocarcinoma, therapeutic targeting of the Rac1 pathway may prevent or reverse EMT and CSC phenotypes that drive tumor progression, metastasis, and chemotherapy resistance. Mol

Enhancement of Radiation Effects by Ursolic Acid in BGC-823 Human Adenocarcinoma Gastric Cancer Cell Line.

Directory of Open Access Journals (Sweden)

Yang Yang

Full Text Available Recent research has suggested that certain plant-derived polyphenols, i.e., ursolic acid (UA, which are reported to have antitumor activities, might be used to sensitize tumor cells to radiation therapy by inhibiting pathways leading to radiation therapy resistance. This experiment was designed to investigate the effects and possible mechanism of radiosensitization by UA in BGC-823 cell line from human adenocarcinoma gastric cancer in vitro. UA caused cytotoxicity in a dose-dependent manner, and we used a sub-cytotoxicity concentration of UA to test radioenhancement efficacy with UA in gastric cancer. Radiosensitivity was determined by clonogenic survival assay. Surviving fraction of the combined group with irradiation and sub-cytotoxicity UA significantly decreased compared with the irradiation group. The improved radiosensitization efficacy was associated with enhanced G2/M arrest, increased reactive oxygen species (ROS, down-regulated Ki-67 level and improved apoptosis. In conclusion, as UA demonstrated potent antiproliferation effect and synergistic effect, it could be used as a potential drug sensitizer for the application of radiotherapy.

Gastric type mucinous endocervical adenocarcinoma of the uterine cervix: very rare and interesting case.

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Park, Chul Min; Koh, Hyun Min; Park, Soyun; Kang, Hye Sim; Shim, Soon Sup; Kim, Sung Yob

2018-01-01

Gastric type mucinous endocervical adenocarcinomas of the uterine cervix (GAC) are a newly classified mucinous subtype with morphologically in 2014, WHO. They have a much more aggressiveness and show unusual metastatic patterns compared to usual type endocervical adenocarcinoma. They tend to present at higher stage and even in stage I, they have worse survival. Therefore, differential diagnosis of GAC from the usual type of endocervical adenocarcinoma is very important because they are related to a significant risk of recurrence and decreased 5-year disease-specific survival. Besides, GACs are mostly not associated with human papillomavirus (HPV) infection and p16 immunohistochemistry is also typically negative in GAC that is HPV-unassociated tumor. We report a very rare and interesting case of stage IB1 GAC with negative HPV DNA and p16.

Comprehensive molecular characterization of gastric adenocarcinoma

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Bass, Adam J.; Thorsson, Vesteinn; Shmulevich, Ilya; Reynolds, Sheila M.; Miller, Michael; Bernard, Brady; Hinoue, Toshinori; Laird, Peter W.; Curtis, Christina; Shen, Hui; Weisenberger, Daniel J.; Schultz, Nikolaus; Shen, Ronglai; Weinhold, Nils; Kelsen, David P.; Bowlby, Reanne; Chu, Andy; Kasaian, Katayoon; Mungall, Andrew J.; Robertson, A. Gordon; Sipahimalani, Payal; Cherniack, Andrew; Getz, Gad; Liu, Yingchun; Noble, Michael S.; Pedamallu, Chandra; Sougnez, Carrie; Taylor-Weiner, Amaro; Akbani, Rehan; Lee, Ju-Seog; Liu, Wenbin; Mills, Gordon B.; Yang, Da; Zhang, Wei; Pantazi, Angeliki; Parfenov, Michael; Gulley, Margaret; Piazuelo, M. Blanca; Schneider, Barbara G.; Kim, Jihun; Boussioutas, Alex; Sheth, Margi; Demchok, John A.; Rabkin, Charles S.; Willis, Joseph E.; Ng, Sam; Garman, Katherine; Beer, David G.; Pennathur, Arjun; Raphael, Benjamin J.; Wu, Hsin-Ta; Odze, Robert; Kim, Hark K.; Bowen, Jay; Leraas, Kristen M.; Lichtenberg, Tara M.; Weaver, Stephanie; McLellan, Michael; Wiznerowicz, Maciej; Sakai, Ryo; Getz, Gad; Sougnez, Carrie; Lawrence, Michael S.; Cibulskis, Kristian; Lichtenstein, Lee; Fisher, Sheila; Gabriel, Stacey B.; Lander, Eric S.; Ding, Li; Niu, Beifang; Ally, Adrian; Balasundaram, Miruna; Birol, Inanc; Bowlby, Reanne; Brooks, Denise; Butterfield, Yaron S. N.; Carlsen, Rebecca; Chu, Andy; Chu, Justin; Chuah, Eric; Chun, Hye-Jung E.; Clarke, Amanda; Dhalla, Noreen; Guin, Ranabir; Holt, Robert A.; Jones, Steven J.M.; Kasaian, Katayoon; Lee, Darlene; Li, Haiyan A.; Lim, Emilia; Ma, Yussanne; Marra, Marco A.; Mayo, Michael; Moore, Richard A.; Mungall, Andrew J.; Mungall, Karen L.; Nip, Ka Ming; Robertson, A. Gordon; Schein, Jacqueline E.; Sipahimalani, Payal; Tam, Angela; Thiessen, Nina; Beroukhim, Rameen; Carter, Scott L.; Cherniack, Andrew D.; Cho, Juok; Cibulskis, Kristian; DiCara, Daniel; Frazer, Scott; Fisher, Sheila; Gabriel, Stacey B.; Gehlenborg, Nils; Heiman, David I.; Jung, Joonil; Kim, Jaegil; Lander, Eric S.; Lawrence, Michael S.; Lichtenstein, Lee; Lin, Pei; Meyerson, Matthew; Ojesina, Akinyemi I.; Pedamallu, Chandra Sekhar; Saksena, Gordon; Schumacher, Steven E.; Sougnez, Carrie; Stojanov, Petar; Tabak, Barbara; Taylor-Weiner, Amaro; Voet, Doug; Rosenberg, Mara; Zack, Travis I.; Zhang, Hailei; Zou, Lihua; Protopopov, Alexei; Santoso, Netty; Parfenov, Michael; Lee, Semin; Zhang, Jianhua; Mahadeshwar, Harshad S.; Tang, Jiabin; Ren, Xiaojia; Seth, Sahil; Yang, Lixing; Xu, Andrew W.; Song, Xingzhi; Pantazi, Angeliki; Xi, Ruibin; Bristow, Christopher A.; Hadjipanayis, Angela; Seidman, Jonathan; Chin, Lynda; Park, Peter J.; Kucherlapati, Raju; Akbani, Rehan; Ling, Shiyun; Liu, Wenbin; Rao, Arvind; Weinstein, John N.; Kim, Sang-Bae; Lee, Ju-Seog; Lu, Yiling; Mills, Gordon; Laird, Peter W.; Hinoue, Toshinori; Weisenberger, Daniel J.; Bootwalla, Moiz S.; Lai, Phillip H.; Shen, Hui; Triche, Timothy; Van Den Berg, David J.; Baylin, Stephen B.; Herman, James G.; Getz, Gad; Chin, Lynda; Liu, Yingchun; Murray, Bradley A.; Noble, Michael S.; Askoy, B. Arman; Ciriello, Giovanni; Dresdner, Gideon; Gao, Jianjiong; Gross, Benjamin; Jacobsen, Anders; Lee, William; Ramirez, Ricardo; Sander, Chris; Schultz, Nikolaus; Senbabaoglu, Yasin; Sinha, Rileen; Sumer, S. Onur; Sun, Yichao; Weinhold, Nils; Thorsson, Vésteinn; Bernard, Brady; Iype, Lisa; Kramer, Roger W.; Kreisberg, Richard; Miller, Michael; Reynolds, Sheila M.; Rovira, Hector; Tasman, Natalie; Shmulevich, Ilya; Ng, Santa Cruz Sam; Haussler, David; Stuart, Josh M.; Akbani, Rehan; Ling, Shiyun; Liu, Wenbin; Rao, Arvind; Weinstein, John N.; Verhaak, Roeland G.W.; Mills, Gordon B.; Leiserson, Mark D. M.; Raphael, Benjamin J.; Wu, Hsin-Ta; Taylor, Barry S.; Black, Aaron D.; Bowen, Jay; Carney, Julie Ann; Gastier-Foster, Julie M.; Helsel, Carmen; Leraas, Kristen M.; Lichtenberg, Tara M.; McAllister, Cynthia; Ramirez, Nilsa C.; Tabler, Teresa R.; Wise, Lisa; Zmuda, Erik; Penny, Robert; Crain, Daniel; Gardner, Johanna; Lau, Kevin; Curely, Erin; Mallery, David; Morris, Scott; Paulauskis, Joseph; Shelton, Troy; Shelton, Candace; Sherman, Mark; Benz, Christopher; Lee, Jae-Hyuk; Fedosenko, Konstantin; Manikhas, Georgy; Potapova, Olga; Voronina, Olga; Belyaev, Smitry; Dolzhansky, Oleg; Rathmell, W. Kimryn; Brzezinski, Jakub; Ibbs, Matthew; Korski, Konstanty; Kycler, Witold; ŁaŸniak, Radoslaw; Leporowska, Ewa; Mackiewicz, Andrzej; Murawa, Dawid; Murawa, Pawel; Spychała, Arkadiusz; Suchorska, Wiktoria M.; Tatka, Honorata; Teresiak, Marek; Wiznerowicz, Maciej; Abdel-Misih, Raafat; Bennett, Joseph; Brown, Jennifer; Iacocca, Mary; Rabeno, Brenda; Kwon, Sun-Young; Penny, Robert; Gardner, Johanna; Kemkes, Ariane; Mallery, David; Morris, Scott; Shelton, Troy; Shelton, Candace; Curley, Erin; Alexopoulou, Iakovina; Engel, Jay; Bartlett, John; Albert, Monique; Park, Do-Youn; Dhir, Rajiv; Luketich, James; Landreneau, Rodney; Janjigian, Yelena Y.; Kelsen, David P.; Cho, Eunjung; Ladanyi, Marc; Tang, Laura; McCall, Shannon J.; Park, Young S.; Cheong, Jae-Ho; Ajani, Jaffer; Camargo, M. Constanza; Alonso, Shelley; Ayala, Brenda; Jensen, Mark A.; Pihl, Todd; Raman, Rohini; Walton, Jessica; Wan, Yunhu; Demchok, John A.; Eley, Greg; Mills Shaw, Kenna R.; Sheth, Margi; Tarnuzzer, Roy; Wang, Zhining; Yang, Liming; Zenklusen, Jean Claude; Davidsen, Tanja; Hutter, Carolyn M.; Sofia, Heidi J.; Burton, Robert; Chudamani, Sudha; Liu, Jia

2014-01-01

Gastric cancer is a leading cause of cancer deaths, but analysis of its molecular and clinical characteristics has been complicated by histological and aetiological heterogeneity. Here we describe a comprehensive molecular evaluation of 295 primary gastric adenocarcinomas as part of The Cancer Genome Atlas (TCGA) project. We propose a molecular classification dividing gastric cancer into four subtypes: tumours positive for Epstein–Barr virus, which display recurrent PIK3CA mutations, extreme DNA hypermethylation, and amplification of JAK2, CD274 (also known as PD-L1) and PDCD1LG2 (also knownasPD-L2); microsatellite unstable tumours, which show elevated mutation rates, including mutations of genes encoding targetable oncogenic signalling proteins; genomically stable tumours, which are enriched for the diffuse histological variant and mutations of RHOA or fusions involving RHO-family GTPase-activating proteins; and tumours with chromosomal instability, which show marked aneuploidy and focal amplification of receptor tyrosine kinases. Identification of these subtypes provides a roadmap for patient stratification and trials of targeted therapies. PMID:25079317

Efficacy of Omega Fatty Acid Supplementation on mRNA Expression Level of Tumor Necrosis Factor Alpha in Patients with Gastric Adenocarcinoma.

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Hosseinzadeh, Asghar; Ardebili, Seyed Mojtaba Mohaddes

2016-09-01

Tumor necrosis factor alpha (TNF-α), a multifunctional cytokine, is involved in apoptosis, cell proliferation, cell survival, and inflammation. It plays a dual role in cancer development and progression. It has been revealed that polyunsaturated fatty acids (PUFAs) modulate the production and activity of TNF family cytokines. The objective of the present study was to evaluate the effect of PUFAs on messenger RNA expression levels of TNF-α in patients with gastric adenocarcinoma. Thirty-four chemotherapy-naive patients diagnosed with gastric adenocarcinoma were randomly divided into two groups. The first group (17 individuals) received cisplatin without supplements and the second group (17 individuals) received cisplatin plus orally administered PUFA supplements for 3 weeks, based on treatment strategies. The gastric biopsy samples were obtained from all participants before and after treatment, and TNF-α mRNA expression levels were evaluated by quantitative real-time PCR procedure. Our findings revealed that TNF-α mRNA expression is downregulated in group II, after receiving cisplatin and omega fatty acid supplement for 3 weeks. However, this difference is not statistically significant (p > 0.05). TNF-α mRNA expression did not show significant alteration in group I, after receiving cisplatin alone. Taken together, we concluded that omega fatty acids reduce TNF-α expression at the mRNA level in patients with gastric adenocarcinoma. These data suggest that TNF-α may act as a potential target for the therapy of human gastric adenocarcinoma.

Loss of gastric gland mucin-specific O-glycan is associated with progression of differentiated-type adenocarcinoma of the stomach.

Science.gov (United States)

Shiratsu, Kazuo; Higuchi, Kayoko; Nakayama, Jun

2014-01-01

Gastric gland mucin secreted from the lower portion of the gastric mucosa contains unique O-linked oligosaccharides having terminal α1,4-linked N-acetylglucosamine (αGlcNAc) residues largely attached to a MUC6 scaffold. Previously, we generated A4gnt-deficient mice, which totally lack αGlcNAc, and showed that αGlcNAc functions as a tumor suppressor for gastric cancer. Here, to determine the clinicopathological significance of αGlcNAc in gastric carcinomas, we examined immunohistochemical expression of αGlcNAc and mucin phenotypic markers including MUC5AC, MUC6, MUC2, and CD10 in 214 gastric adenocarcinomas and compared those expression patterns with clinicopathological parameters and cancer-specific survival. The αGlcNAc loss was evaluated in MUC6-positive gastric carcinoma. Thirty-three (61.1%) of 54 differentiated-type gastric adenocarcinomas exhibiting MUC6 in cancer cells lacked αGlcNAc expression. Loss of αGlcNAc was significantly correlated with depth of invasion, stage, and venous invasion by differentiated-type adenocarcinoma. Loss of αGlcNAc was also significantly associated with poorer patient prognosis in MUC6-positive differentiated-type adenocarcinoma. By contrast, no significant correlation between αGlcNAc loss and any clinicopathologic variable was observed in undifferentiated-type adenocarcinoma. Expression of MUC6 was also significantly correlated with several clinicopathological variables in differentiated-type adenocarcinoma. However, unlike the case with αGlcNAc, its expression showed no correlation with cancer-specific survival in patients. In undifferentiated-type adenocarcinoma, we observed no significant correlation between mucin phenotypic marker expression, including MUC6, and any clinicopathologic variable. These results together indicate that loss of αGlcNAc in MUC6-positive cancer cells is associated with progression and poor prognosis in differentiated, but not undifferentiated, types of gastric adenocarcinoma. © 2013 The

Body mass index, height and risk of adenocarcinoma of the oesophagus and gastric cardia: A prospective cohort study

NARCIS (Netherlands)

Merry, A.H.H.; Schouten, L.J.; Goldbohm, R.A.; Brandt, P.A. van den

2007-01-01

Background: In the last decades, the incidence of oesophageal and gastric cardia adenocarcinoma has increased rapidly in the Western world. We investigated the association between body mass index (BMI), height and risk of oesophageal and gastric cardia adenocarcinoma. Methods: The Netherlands Cohort

Gastric extremely well differentiated adenocarcinoma of gastric phenotype: as a gastric counterpart of adenoma malignum of the uterine cervix

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Ae Lee Won

2005-05-01

Full Text Available Abstract Background Most of gastric adenocarcinoma can be simply diagnosed by microscopic examination of biopsy specimen. Rarely the structural and cellular atypia of tumor cells is too insignificant to discriminate from benign foveolar epithelium. Case presentation A 67-year-old male presented with a gastric mass incidentally found on the abdominal computed tomography (CT for routine medical examination. Gastric endoscopic examination revealed a huge fungating mass at the cardia and mucosal biopsy was performed. Microscopically the biopsy specimen showed proliferation of bland looking foveolar epithelia in the inflammatory background and diagnosed as foveolar epithelial hyperplasia. Because the clinical and endoscopic features of this patient were strongly suggestive of malignancy, the patient underwent radical total gastrectomy. The resected stomach revealed a huge fungating tumor at the cardia. The cut surface of the tumor was whitish gelatinous. Microscopically the tumor was sharply demarcated from surrounding mucosa and composed of very well formed glandular structures without significant cellular atypia, which invaded into the whole layer of the gastric wall. Tumor glands were occasionally complicated or dilated, and glandular lumina were filled with abundant mucin. Immunohistochemically the tumor cells revealed no overexpression of p53 protein but high Ki-67 labeling index. The tumor cells and intraluminal mucin were diffusely expressed MUC1 and MUC5AC and only focally expressed MUC2. On abdominal CT taken after 12 months demonstrated peritoneal carcinomatosis and multiple metastatic foci in the lung. Conclusion The clinicopathologic profiles of gastric extremely well differentiated adenocarcinoma of gastric phenotype include cardiac location, fungating gross type, very similar histology to foveolar epithelial hyperplasia, foveolar mucin phenotype, lack of p53 overexpressoin and high proliferative index.

Undifferentiated-type gastric adenocarcinoma: prognostic impact of three histological types

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Lee Han

2012-11-01

Full Text Available Abstract Background The prognostic value of the three constituents of undifferentiated-type gastric adenocarcinoma remains unclear. The present study assessed the clinicopathological characteristics and prognosis of undifferentiated-type mucinous adenocarcinoma (uMAC and signet ring cell carcinoma (SRC compared with those of poorly differentiated adenocarcinoma (PDAC. Methods In total, 1,376 patients with undifferentiated-type gastric adenocarcinoma were included, consisting of 1,002 patients diagnosed with PDAC, 54 with uMAC and 320 with SRC. Clinicopathological factors and survival rates were compared among the three histological types. Results Significant differences in the distribution of pathological stages were observed among the groups. Patients with SRC had a significantly better survival rate than those with PDAC or uMAC, in both the all patients including non-curative resected patients and curative-resected groups. In addition, there was significant difference in survival between the PDAC and uMAC groups. Multivariate analysis suggested that age, gender, tumor depth, lymph node metastasis and curability significantly affected survival. Histological type was not an independent prognostic factor. There was no significant difference in the pattern of recurrence among the three groups. Conclusions The uMAC and SRC had worse and favorable prognosis compared with PDCA, respectively. However, there were no differences in survival by pathological stage, thus histological type was not an independent predictor of prognosis.

Cereal fiber intake may reduce risk of gastric adenocarcinomas : The EPIC-EURGAST study

NARCIS (Netherlands)

Mendez, M. A.; Pera, Guillem; Aguclo, Antonio; Bueno-de-Mesquita, H. Bas; Palli, Domenico; Boeing, Heiner; Carneiro, Ftima; Berrino, Franco; Sacerdote, Carlotta; Tumino, Rosario; Panico, Salvatore; Berglund, Goeran; Manjer, Jonas; Johansson, Ingegerd; Stenling, Roger; Martinez, Carmen; Dorronsoro, Miren; Barricarte, Aurelio; Tormo, Maria J.; Quiros, Jose R.; Allen, Naomi; Key, Timothy J.; Bingham, Sheila; Linseisen, Jakob; Kaaks, Rudolf; Overvad, Kim; Jensen, Majken; Olsen, Anja; Tjonneland, Anne; Peeters, Petra H. M.; Numans, Mattijs E.; Ocke, Marga C.; Clavel-Chapelon, Francoise; Boutron-Ruault, Marie-Christine; Trichopoulou, Antonia; Lund, Eiliv; Slimani, Nadia; Jenab, Mazda; Ferrari, Pietro; Riboli, Elio; Gonzalez, Carlos A.

2007-01-01

Numerous case-control studies suggest dietary fiber may reduce risk of gastric cancer, but this has not been confirmed prospectively. A previous case-control study reported reduced risk of gastric cardia adenocarcinomas associated with cereal fiber, but not with fruit or vegetable fiber. To date,

Expression of p53 protein in Barrett’s adenocarcinoma and adenocarcinoma of the gastric cardia and antrum

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Jovanović Ivan

2005-01-01

Full Text Available Background/Aim. Most studies of esophageal and gastric adenocarcinomas have shown a very high rate of p53 gene mutation and/or protein overexpression, but the influence of the tumor site upon the frequency of p53 protein expression has not been evaluated (gastroesophageal junction, Barret's esophagus, and antrum. The aim of our study was to analyze the correlation between the selected clinico-pthological parameters, and p53 protein overexpression in regards to the particular tumor location. Methods. The material comprised 66 surgical specimens; 10 were Barrett’s carcinomas, 25 adenocarcinomas of the gastric cardia (type II adenocarcinoma of the esophagogastric junction - EGJ, and 31 adenocarcinomas of the antrum. Immunostaining for p53 protein was performed on formalin-fixed, paraffin-embedded tissue sections, using the alkaline phosphatase - antialkaline phosphatase (APAAP method. The cases were considered positive for p53 if at least 5% of the tumor cells expressed this protein by immunostaining. Results. There was no significant difference observed between the studied groups in regards to age, sex, Lauren’s classification and tumor differentiation. There was, however, a significant difference observed in the depth of tumor invasion between Barrrett’s adenocarcinoma and adenocarcinoma of the cardia compared with the adenocarcinoma of the antrum. Namely, at the time of surgery, both Barrett’s adenocarcinomas and adenocarcinomas of the cardia, were significantly more advanced comparing with the adenocarcinomas of the antrum. Overexpression of p53 was found in 40% (4/10 of Barrett’s adenocarcinomas, 72% (18/25 of adenocarcinoma of the cardia and 65% (20/31 of adenocarcinoma of the antrum. No significant differences in p53 expression in relation to sex, type (Lauren of tumor, depth of invasion, lymph node involvement, or tumor differentiation were observed in any of the analyzed groups of tumors. Patients with more advanced Barrett�

Multidetector computed tomography in the preoperative staging of gastric adenocarcinoma

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Barros, Ricardo Hoelz de Oliveira; Penachim, Thiago Jose; Martins, Daniel Lahan; Andreollo, Nelson Adami; Caserta, Nelson Marcio Gomes, E-mail: rhobarros@hotmail.com [Universidade Estadual de Campinas (UNICAMP), Campinas, SP (Brazil)

2015-03-15

Objective: To evaluate the role of multidetector computed tomography in the preoperative investigation of tumor invasion depth and lymph node and metastatic involvement according to the TNM classification, in patients with gastric adenocarcinoma. Materials and Methods: Fifty-four patients with biopsy-confirmed gastric cancer underwent preoperative staging with 64-channel multidetector computed tomography. Two independent radiologists analyzed the images and classified the findings. Sensitivity, specificity, accuracy and overall accuracy were calculated for each observer. The interobserver agreement was also evaluated. Results: The accuracy in the classification of categories T ranged from 74% to 96% for observer 1 and from 80% to 92% for observer 2. The overall accuracy was 70% for both observers. The weighted kappa index was 0.75, consistent with a significant interobserver agreement. The accuracy in the classification of lymph node involvement (category N) ranged from 55% to 79% for observer 1 and from 73% to 82% for observer 2. The evaluation of metastatic involvement showed an overall accuracy of 89.6% for both observers. Conclusion: 64-channel multidetector computed tomography demonstrated clinically relevant accuracy in the preoperative staging of gastric adenocarcinoma as regards invasion depth (T category) and metastatic involvement (M category). (author)

Multidetector computed tomography in the preoperative staging of gastric adenocarcinoma

International Nuclear Information System (INIS)

Barros, Ricardo Hoelz de Oliveira; Penachim, Thiago Jose; Martins, Daniel Lahan; Andreollo, Nelson Adami; Caserta, Nelson Marcio Gomes

2015-01-01

Objective: To evaluate the role of multidetector computed tomography in the preoperative investigation of tumor invasion depth and lymph node and metastatic involvement according to the TNM classification, in patients with gastric adenocarcinoma. Materials and Methods: Fifty-four patients with biopsy-confirmed gastric cancer underwent preoperative staging with 64-channel multidetector computed tomography. Two independent radiologists analyzed the images and classified the findings. Sensitivity, specificity, accuracy and overall accuracy were calculated for each observer. The interobserver agreement was also evaluated. Results: The accuracy in the classification of categories T ranged from 74% to 96% for observer 1 and from 80% to 92% for observer 2. The overall accuracy was 70% for both observers. The weighted kappa index was 0.75, consistent with a significant interobserver agreement. The accuracy in the classification of lymph node involvement (category N) ranged from 55% to 79% for observer 1 and from 73% to 82% for observer 2. The evaluation of metastatic involvement showed an overall accuracy of 89.6% for both observers. Conclusion: 64-channel multidetector computed tomography demonstrated clinically relevant accuracy in the preoperative staging of gastric adenocarcinoma as regards invasion depth (T category) and metastatic involvement (M category). (author)

Characterization of gastric adenocarcinoma cell lines established from CEA424/SV40 T antigen-transgenic mice with or without a human CEA transgene

International Nuclear Information System (INIS)

Nöckel, Jessica; Engel, Natasja K van den; Winter, Hauke; Hatz, Rudolf A; Zimmermann, Wolfgang; Kammerer, Robert

2006-01-01

Gastric carcinoma is one of the most frequent cancers worldwide. Patients with gastric cancer at an advanced disease stage have a poor prognosis, due to the limited efficacy of available therapies. Therefore, the development of new therapies, like immunotherapy for the treatment of gastric cancer is of utmost importance. Since the usability of existing preclinical models for the evaluation of immunotherapies for gastric adenocarcinomas is limited, the goal of the present study was to establish murine in vivo models which allow the stepwise improvement of immunotherapies for gastric cancer. Since no murine gastric adenocarcinoma cell lines are available we established four cell lines (424GC, mGC3, mGC5, mGC8) from spontaneously developing tumors of CEA424/SV40 T antigen (CEA424/Tag) mice and three cell lines derived from double-transgenic offsprings of CEA424/Tag mice mated with human carcinoembryonic antigen (CEA)-transgenic (CEA424/Tag-CEA) mice (mGC2 CEA , mGC4 CEA , mGC11 CEA ). CEA424/Tag is a transgenic C57BL/6 mouse strain harboring the Tag under the control of a -424/-8 bp CEA gene promoter which leads to the development of invasive adenocarcinoma in the glandular stomach. Tumor cell lines established from CEA424/Tag-CEA mice express the well defined tumor antigen CEA under the control of its natural regulatory elements. The epithelial origin of the tumor cells was proven by morphological criteria including the presence of mucin within the cells and the expression of the cell adhesion molecules EpCAM and CEACAM1. All cell lines consistently express the transgenes CEA and/or Tag and MHC class I molecules leading to their susceptibility to lysis by Tag-specific CTL in vitro. Despite the presentation of CTL-epitopes derived from the transgene products the tumor cell lines were tumorigenic when grafted into C57BL/6, CEA424/Tag or CEA424/Tag-CEA-transgenic hosts and no significant differences in tumor take and tumor growth were observed in the different hosts

MET overexpression, gene amplification and relevant clinicopathological features in gastric adenocarcinoma.

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Zhang, Jing; Guo, Lei; Liu, Xiuyun; Li, Wenbin; Ying, Jianming

2017-02-07

This study was conducted to investigate the expression of MET in Chinese gastric adenocarcinoma cohort, the correlation between MET overexpression and clinical pathological features, HER2 expression and MET gene amplification. A total of 816 gastric adenocarcinoma patients were included and MET and HER2 immunohistochemical (IHC) staining were performed. IHC and dual-color silver in situ hybridization analysis were performed in the tissue microarrays, constructed from the 240 patients who were randomly selected. MET overexpression (IHC 3+) was observed in 6.0% (49/816) of the cohort. MET overexpression rate was higher in patients with poor prognostic factors, such as clinical stages III/IV (p =0.012) and pathologic stages T3/T4 (p =0.027). The HER2 overexpression (IHC 3+) rate was 8.8% (72/816) and MET overexpression rate was higher in HER2 positive patients (9.7%, 7/72). A high concordance rate (94.6%) between MET overexpression and gene amplification was demonstrated. Therefore, MET overexpression could serve as a prognostic biomarker and a potential therapeutic target for gastric cancer.

Gastric outlet obstruction due to adenocarcinoma in a patient with Ataxia-Telangiectasia syndrome: a case report and review of the literature

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Hammond Sue

2009-03-01

Full Text Available Abstract Background Ataxia-Telangiectasia syndrome is characterized by progressive cerebellar dysfunction, conjuctival and cutaneous telangiectasias, severe immune deficiencies, premature aging and predisposition to cancer. Clinical and radiographic evaluation for malignancy in ataxia-telangiectasia patients is usually atypical, leading to delays in diagnosis. Case presentation We report the case of a 20 year old ataxia-telangiectasia patient with gastric adenocarcinoma that presented as complete gastric outlet obstruction. Conclusion A literature search of adenocarcinoma associated with ataxia-telangiectasia revealed 6 cases. All patients presented with non-specific gastrointestinal complaints suggestive of ulcer disease. Although there was no correlation between immunoglobulin levels and development of gastric adenocarcinoma, the presence of chronic gastritis and intestinal metaplasia seem to lead to the development of gastric adenocarcinoma. One should consider adenocarcinoma in any patient with ataxia-telangiectasia who presents with non-specific gastrointestinal complaints, since this can lead to earlier diagnosis.

Apoptotic-like tumor cells and apoptotic neutrophils in mitochondrion-rich gastric adenocarcinomas: a comparative study with light and electronmicroscopy between these two forms of cell death

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Antonio Venuti

2013-04-01

Full Text Available Mitochondrion-rich adenocarcinomas represent a rare variant of gastric adenocarcinomas composed predominantly of columnar adenocarcinoma cells with eosinophilic cytoplasm, a strong supranuclear immunoreactivity for antimitochondrial antibody, and a marked neutrophil infiltration associated to tumor cell death. The purpose of this work is to investigate, using correlated light and electron microscopy, mitochondrion-rich gastric adenocarcinomas focusing on the nature of the death in neoplastic cells and in infiltrating neutrophils. Adenocarcinoma cells, single or in small clusters, showed convoluted nuclei, irregularly condensed chromatin, loss of microvilli, and nuclear envelope dilatation. No nuclear fragmentation was observed in these dying cells and the plasma membrane did not show signs of disruption. These ultrastructural findings represent intermediate aspects between apoptosis and necrosis and are compatible with apoptosis-like programmed cell death. By contrast, some infiltrating neutrophils showed ultrastructural signs of classic apoptosis such as chromatin condensation into compact geometric (globular, crescent-shaped figures, tightly packed cytoplasmic granules and intact cell membrane. Our study provides ultrastructural evidence of apoptosis-like tumour cell death in mitochondrion-rich gastric carcinomas and confirms that stereotyped outcome either as apoptosis or necrosis of tumor cells cannot always be expected in human neoplasms.

Widespread hematogenous metastases and Trousseau's syndrome in gastric adenocarcinoma

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Santos Vitorino Modesto dos

2001-01-01

Full Text Available A case of widespread hematogenous metastases and Trousseau's syndrome is reported in a 40 year-old white housewife with gastric cancer, presenting subdural hematoma, ecchymoses, epistaxis, stomach and uterine bleeding. After undergoing hematoma drainage, she was unsuccessfully treated with platelets, red blood cells, plasma cryoprecipitate transfusions, and antibiotics. Necropsy disclosed gastric ring-signet adenocarcinoma invading the serous layer, with massive disseminated intravascular coagulation and systemic neoplastic embolism. Multiple old and recent hyaline (rich in fibrin and platelets microthrombi, and tumor emboli were observed in the bone marrow, meninges, liver, lungs, kidneys, lymph nodes, adrenals, thyroid, heart, pancreas, and ovaries (Krukenberg tumor.

[Increased expressions of peripheral PD-1+ lymphocytes and CD4+CD25+FOXP3+ T cells in gastric adenocarcinoma patients].

Science.gov (United States)

Li, Hao; Li, Songyan; Hu, Shidong; Zou, Guijun; Hu, Zilong; Wei, Huahua; Wang, Yufeng; Du, Xiaohui

2017-01-01

Objective To detect the frequencies of peripheral programmed death-1 + (PD-1 + ) lymphocytes and CD4 + CD25 + FOXP3 + regulatory T cells in patients with gastric adenocarcinoma. Methods The study enrolled 29 patients with gastric adenocarcinoma and 29 age- and sex-matched healthy controls. Frequencies of PD-1 + lymphocytes and CD4 + CD25 + FOXP3 + regulatory T cells were detected using flow cytometry. Results The number of PD-1 + lymphocytes and CD4 + CD25 + FOXP3 + regulatory T cells in peripheral blood was higher in patients with gastric adenocarcinoma than that in the control group. Moreover, linear correlation analysis indicated a positive correlation between PD-1 expression and frequency of CD4 + CD25 + FOXP3 + regulatory T cells in peripheral blood of the patients. Conclusion Gastric adenocarcinoma patients present with increased PD-1 + lymphocytes and CD4 + CD25 + FOXP3 + regulatory T cells in the peripheral blood.

Gastric adenocarcinoma in common variable immunodeficiency: features of cancer and associated gastritis may be characteristic of the condition.

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De Petris, Giovanni; Dhungel, Bal M; Chen, Longwen; Chang, Yu-Hui H

2014-10-01

Common variable immunodeficiency (CVID) is associated with an increased risk of gastric cancer. The aim of the study was to determine the morphological features of CVID-associated gastric adenocarcinoma (CAGA) and of the background gastritis. The population of gastric cancer patients with CVID of Mayo Clinic in the period 2000-2010 was studied; 6 cases of CVID (2 males, 4 females, average age 47 years, age range 26-71 years) were found in 5793 patients with gastric cancer in the study period. Each patient underwent gastric resection for which histology slides were reviewed. Chronic gastritis variables, CVID-related findings, and features of the adenocarcinoma were recorded. CAGA was of intestinal type, with high number of intratumoral lymphocytes (ITLs). Cancer was diagnosed in younger patients than in the overall population of gastric cancer. Severe atrophic metaplastic pangastritis with extensive dysplasia was present in the background in 4 cases, with features of lymphocytic gastritis in 2 cases. Features of CVID (plasma cells paucity in 4 of 6 cases, lymphoid nodules prominent in four cases) could be detected. In summary, gastric adenocarcinoma at young age with ITLs, accompanied by atrophic metaplastic pangastritis, should alert the pathologist of the possibility of CAGA. It follows that, in presence of those characteristics, the search of CVID-associated abnormalities should be undertaken in the nonneoplastic tissues. © The Author(s) 2014.

Enterococcus faecalis Infection and Reactive Oxygen Species Down-Regulates the miR-17-92 Cluster in Gastric Adenocarcinoma Cell Culture

DEFF Research Database (Denmark)

Strickertsson, Jesper A B; Rasmussen, Lene Juel; Friis-Hansen, Lennart

2014-01-01

Chronic inflammation due to bacterial overgrowth of the stomach predisposes to the development of gastric cancer and is also associated with high levels of reactive oxygen species (ROS). In recent years increasing attention has been drawn to microRNAs (miRNAs) due to their role in the pathogenesis...... of many human diseases including gastric cancer. Here we studied the impact of infection by the gram-positive bacteria Enterococcus faecalis (E. faecalis) on global miRNA expression as well as the effect of ROS on selected miRNAs. Human gastric adenocarcinoma cell line MKN74 was infected with living E...... by living E. faecalis bacteria caused a significant global response in miRNA expression in the MKN74 cell culture. E. faecalis infection as well as ROS stimulation down-regulated the expression of the miR-17-92 cluster. We believe that these changes could reflect a general response of gastric epithelial...

Timing of chemotherapy and survival in patients with resectable gastric adenocarcinoma

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Arrington, Amanda K; Nelson, Rebecca; Patel, Supriya S; Luu, Carrie; Ko, Michelle; Garcia-Aguilar, Julio; Kim, Joseph

2013-01-01

AIM: To evaluate the timing of chemotherapy in gastric cancer by comparing survival outcomes in treatment groups. METHODS: Patients with surgically resected gastric adenocarcinoma from 1988 to 2006 were identified from the Los Angeles County Cancer Surveillance Program. To evaluate the population most likely to receive and/or benefit from adjunct chemotherapy, inclusion criteria consisted of Stage II or III gastric cancer patients > 18 years of age who underwent curative-intent surgical resection. Patients were categorized into three groups according to the receipt of chemotherapy: (1) no chemotherapy; (2) preoperative chemotherapy; or (3) postoperative chemotherapy. Clinical and pathologic characteristics were compared across the different treatment arms. RESULTS: Of 1518 patients with surgically resected gastric cancer, 327 (21.5%) received perioperative chemotherapy. The majority of these 327 patients were male (68%) with a mean age of 61.5 years; and they were significantly younger than non-chemotherapy patients (mean age, 70.7; P advanced gastric cancer. CONCLUSION: This study supports the implementation of a randomized trial comparing the timing of perioperative therapy in patients with locally advanced gastric cancer. PMID:24392183

A complete response to S-1 plus cis-diamminedichloroplatinum in advanced-stage esophageal and gastric adenocarcinoma: a case report

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Matsuno Yoritaka

2012-07-01

Full Text Available Abstract Background Complete remission from advanced-stage synchronous double primary (SDP esophageal and gastric adenocarcinoma by chemotherapy alone is rare. We report a case of advanced-stage SDP esophageal and gastric adenocarcinoma in which a complete response to treatment was obtained with S-1 and cis-diamminedichloroplatinum (CDDP. Case presentation The patient was a 74-year-old man referred to our hospital complaining of dysphagia. Gastrointestinal endoscopy was performed and advanced-stage SDP esophageal and gastric adenocarcinoma diagnosed. Computed tomography revealed multiple regional lymph node metastases in the mediastinum. Neoadjuvant chemotherapy with S-1 and CDDP for advanced esophageal and gastric cancer was planned. An endoscopy following two courses of chemotherapy revealed that the esophageal cancer had been replaced with a normal mucosal lesion and the gastric tumor with a scar lesion; the results of biopsies of both were negative for cancer. Computed tomography revealed that the multiple lymph node metastases had disappeared. We diagnosed a complete response to S-1 and CDDP in advanced-stage SDP esophageal and gastric cancer. The patient is still alive with no signs of recurrence 22 months after the disappearance of the original tumor and metastatic lesions without surgical treatment. Conclusion These results suggest that complete remission from advanced-stage esophageal and gastric cancer can be obtained with chemotherapy with S-1 plus CDDP.

High prevalence of osteoporosis in patients with gastric adenocarcinoma following gastrectomy

Institute of Scientific and Technical Information of China (English)

无

2007-01-01

AIM: To evaluate the prevalence and predictive factors of osteoporosis in patients with gastric adenocarcinoma after gastrectomy.METHODS: The study included 133 patients diagnosed with gastric adenocarcinoma but who did not undergo prior diagnostic work-up for osteoporosis. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry (DXA) and vertebral deformity was assessed by plain X-rays. We evaluated the effects of age, sex, body mass index (BMI), anemia, back pain,vertebral deformity, tumor staging, reconstruction type,and past medical history to determine predictive factors of osteoporosis in these patients.RESULTS: The prevalence of osteoporosis in the lumbar spine was 38.3% (male, 28.9%; female, 54.0%), and 15.0% in the femoral neck (male, 10.8%; female,22.0%). The vertebral deformity rate was 46.6% (male,43.4%; female, 52.0%). Age, BMI and hemoglobin correlated with BMD (P ＜ 0.01). In males, anemia and age ＞ 64 years were independent predictive factors of osteoporosis in multivariate analysis. In females, back pain was an independent factor for osteoporosis.CONCLUSION: The results of this study revealed that prevalence of osteoporosis and vertebral bone deformity rate were high in gastric cancer patients, regardless of post-gastrectomy duration and operation type. Early diagnosis and a proper management plan must be established in these patients.

Detection of microsatellite instability but not truncating APC mutations in gastric adenocarcinomas in Brazilian patients

OpenAIRE

Bevilacqua Roberta A.U.; Corvello Cassandra M.; Duarte Ana Paula; Simpson Andrew J.G.

2000-01-01

A crucial role for the adenomatous polyposis colonic (APC) gene in colorectal carcinogenesis has been conclusively established, but, the role of APC in gastric tumors remains controversial. APC mutations have been detected at a relatively high frequency in gastric tumors of Japanese patients, yet such mutations have been reported to be extremely rare in British patients and patients from north-central-Italy. We here report the analysis of 40 primary sporadic gastric adenocarcinomas and 35 pri...

CT differentiation of poorly-differentiated gastric neuroendocrine tumours from well-differentiated neuroendocrine tumours and gastric adenocarcinomas

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Kim, Seong Ho; Kim, Se Hyung; Shin, Cheong-il; Han, Joon Koo; Choi, Byung Ihn [Seoul National University Hospital, Department of Radiology, Jongno-gu, Seoul (Korea, Republic of); Seoul National University Hospital, Institute of Radiation Medicine, Jongno-gu, Seoul (Korea, Republic of); Kim, Min-A [Seoul National University Hospital, Department of Pathology, Jongno-gu, Seoul (Korea, Republic of)

2015-07-15

To evaluate the differential CT features of gastric poorly-differentiated neuroendocrine tumours (PD-NETs) from well-differentiated NETs (WD-NETs) and gastric adenocarcinomas (ADCs) and to suggest differential features of hepatic metastases from gastric NETs and ADCs. Our study population was comprised of 36 patients with gastric NETs (18 WD-NETs, 18 PD-NETs) and 38 patients with gastric ADCs who served as our control group. Multiple CT features were assessed to identify significant differential CT findings of PD-NETs from WD-NETs and ADCs. In addition, CT features of hepatic metastases including the metastasis-to-liver ratio were analyzed to differentiate metastatic NETs from ADCs. The presence of metastatic lymph nodes was the sole differentiator of PD-NETs from WD-NETs (P =.001, odds ratio = 56.67), while the presence of intact overlying mucosa with mucosal tenting was the sole significant CT feature differentiating PD-NETs from ADCs (P =.047, odds ratio = 15.3) For hepatic metastases, metastases from NETs were more hyper-attenuated than those from ADCs. The presence of metastatic LNs and intact overlying mucosa with mucosal tenting are useful CT discriminators of PD-NETs from WD-NETs and ADCs, respectively. In addition, a higher metastasis-to-liver ratio may help differentiate hepatic metastases of gastric NETs from those of gastric ADCs with high accuracy. (orig.)

Gastropericardial Fistula and Candida albicans Pericarditis: A Rare Complication of Gastric Adenocarcinoma Treated with Radiation and Chemotherapy

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Chia-Pei Tang

2009-07-01

Full Text Available Gastropericardial fistula is generally associated with benign gastric diseases and is an uncommon complication of gastric adenocarcinoma. Pericarditis and cardiac tamponade are the ultimate outcome, with extremely high mortality rates. We report a 47-year-old man with gastric adenocarcinoma who had completed radiotherapy and was on scheduled chemotherapy, who presented with fever and chest pain. Gastric adenocarcinoma complicated with gastropericardial fistula and Candida albicans pericarditis were diagnosed and treated successfully with conservative management. Initial chest radiography and computed tomography (CT revealed no evident pericardial air or fluid. However, follow-up panendoscopy 2 weeks later revealed a malignant ulcer with a fistula opening over the lesser curvature of the high body of the stomach. Subsequent chest radiography and CT revealed pneumopericardium with fluid accumulation. Emergent CT-guided pericardial drainage was performed. The fluid was positive for Candida albicans. Total parenteral nutrition and antifungal therapy were administered. The patient refused surgical intervention and survived with medical management alone. This case demonstrates that first, panendoscopy may be safely performed in patients with gastropericardial fistula without significant risk of cardiac tamponade; second, although early diagnosis of gastropericardial fistula is generally important, delayed recognition may not lead to devastating outcomes even in the absence of surgical intervention.

Promoter hypermethylation of CDH1, FHIT, MTAP and PLAGL1 in gastric adenocarcinoma in individuals from Northern Brazil

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Leal, Mariana Ferreira; Lima, Eleonidas Moura; Silva, Patrícia Natália Oliveira; Assumpção, Paulo Pimentel; Calcagno, Danielle Queiroz; Payão, Spencer Luiz Marques; Burbano, Rommel Rodríguez; Smith, Marília de Arruda Cardoso

2007-01-01

AIM: To evaluate the methylation status of CDH1, FHIT, MTAP and PLAGL1 promoters and the association of these findings with clinico-pathological characteristics. METHODS: Methylation-specific PCR (MSP) assay was performed in 13 nonneoplastic gastric adenocarcinoma, 30 intestinal-type gastric adenocarcinoma and 35 diffuse-type gastric adenocarcinoma samples from individuals in Northern Brazil. Statistical analyses were performed using the chi-square or Fisher's exact test to assess associations between methylation status and clinico-pathological characteristics. RESULTS: Hypermethylation frequencies of CDH1, FHIT, MTAP and PLAGL1 promoter were 98.7%, 53.9%, 23.1% and 29.5%, respectively. Hypermethylation of three or four genes revealed a significant association with diffuse-type gastric cancer compared with nonneoplastic cancer. A higher hypermethylation frequency was significantly associated with H pylori infection in gastric cancers, especially with diffuse-type. Cancer samples without lymph node metastasis showed a higher FHIT hypermethylation frequency. MTAP hypermethylation was associated with H pylori in gastric cancer samples, as well as with diffuse-type compared with intestinal-type. In diffuse-type, MTAP hypermethylation was associated with female gender. CONCLUSION: Our findings show differential gene methylation in tumoral tissue, which allows us to conclude that hypermethylation is associated with gastric carcinogenesis. MTAP promoter hypermethylation can be characterized as a marker of diffuse-type gastric cancer, especially in women and may help in diagnosis, prognosis and therapies. The H pylori infectious agent was present in 44.9% of the samples. This infection may be correlated with the carcinogenic process through the gene promoter hypermethylation, especially the MTAP promoter in diffuse-type. A higher H pylori infection in diffuse-type may be due to greater genetic predisposition. PMID:17552003

Loss of heterozygosity and immunohistochemistry of adenocarcinomas of the esophagus and gastric cardia

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Marsman, Willem A.; Birjmohun, Rakesh S.; van Rees, Bastiaan P.; Caspers, Eric; Johan, G.; Offerhaus, A.; Bosma, Piter J.; Jan, J.; van Lanschot, B.

2004-01-01

PURPOSE: Adenocarcinomas of the distal esophagus and gastric cardia are two tumors that have many features in common. They have similar prognoses, treatment modalities, and patterns of dissemination. The etiology is different, with gastroesophageal reflux disease playing a major role for esophageal

Expression of Anion Exchanger 1 Sequestrates p16 in the Cytoplasm in Gastric, Colonic Adenocarcinoma

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Wei-Wei Shen

2007-10-01

Full Text Available p16INK4A (p16 binds to cyclin-dependent kinase 4/6, negatively regulates cell growth. Recent studies have led to an understanding of additional biologic functions for p16; however, the detailed mechanisms involved are still elusive. In this article, we show an unexpected expression of anion exchanger 1 (AEi in the cytoplasm in poorly, moderately differentiated gastric, colonic adenocarcinoma cells, in its interaction with p16, thereby sequestrating the protein in the cytoplasm. Genetic alterations of p16, AEi were not detectable. Forced expression of AEi in these cells sequestrated more p16 in the cytoplasm, whereas small interfering RNA-mediated silencing of AEi in the cells induced the release of p16 from the cytoplasm to the nucleus, leading to cell death, growth inhibition of tumor cells. By analyzing tissue samples obtained from patients with gastric, colonic cancers, we found that 83.33% of gastric cancers, 56.52% of colonic cancers coexpressed AEi, p16 in the cytoplasm. We conclude that AEi plays a crucial role in the pathogenesis of gastric, colonic adenocarcinoma, that p16 dysfunction is a novel pathway of carcinogenesis.

A multicenter, phase II study of bortezomib (PS-341) in patients with unresectable or metastatic gastric and gastroesophageal junction adenocarcinoma.

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Shah, Manish A; Power, Derek G; Kindler, Hedy L; Holen, Kyle D; Kemeny, Margaret M; Ilson, David H; Tang, Laura; Capanu, Marinela; Wright, John J; Kelsen, David P

2011-12-01

The transcription factor nuclear factor-kB (NFkB) is implicated in gastric cancer carcinogenesis and survival, and its inhibition by proteosome inhibition is associated with preclinical gastric cancer anti-tumor activity. We examined the single agent efficacy of bortezomib, a selective proteasome inhibitor, in gastric adenocarcinoma. We performed a phase II trial of bortezomib in patients with advanced gastric adenocarcinoma. Bortezomib 1.3 mg/m(2) was administered on days 1, 4, 8, and 11 every 21 days. The primary endpoint was objective response rate(RR); the null hypothesis was RR <1% versus the alternative ≥15%. One response in the first stage(15 patients) was required before proceeding with an additional 18 patients. If at least 2 or more responses out of 33 were observed, further study with bortezomib was warranted. Correlative studies evaluated pre-treatment tumor expression of NFkB, IkB, p53, p21, and cyclin D1. We enrolled 16 patients (15 evaluable for response) from four institutions. No patients demonstrated an objective response(95% CI, 0-22%); one patient achieved stable disease. Fourteen out of 16 patients experienced ≥ grade 2 toxicity. The most common toxicity was fatigue in six patients (n = 4 grade 2, n = 2 grade 3). Seven patients experienced neuropathy (n = 5 grade 1, and 1 each grade 2 and 3). Seven (60%) had high cytoplasmic staining for NFkB. Single agent bortezomib is inactive in metastatic gastric adenocarcinoma and should not be pursued. Future study of proteasome inhibition in gastric adenocarcinoma should be considered in combination with targeted inhibition of other non-overlapping oncogenic pathways as a potential rational approach.

Gastric Composite Tumor of Alpha Fetoprotein-Producing Carcinoma/Hepatoid Adenocarcinoma and Endocrine Carcinoma with Reference to Cellular Phenotypes

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Akira Suzuki

2012-01-01

Full Text Available Alpha-fetoprotein-producing carcinoma (AFPC/hepatoid adenocarcinoma (HAC and neuroendocrine carcinoma (NEC are uncommon in the stomach. Composite tumors consisting of these carcinomas and their histologic phenotypes are not well known. Between 2002 and 2007, to estimate the prevalence of composite tumors consisting of tubular adenocarcinoma, AFPC/HAC and NEC, we reviewed specimens obtained from 294 consecutive patients treated surgically for gastric cancer. We examined histological phenotype of tumors of AFPC or NEC containing the composite tumor by evaluating immunohistochemical expressions of MUC2, MUC5AC, MUC6, CDX2, and SOX2. Immunohistochemically, AFPC/HAC dominantly showed the intestinal or mixed phenotype, and NEC frequently showed the gastric phenotype. In the composite tumor, the tubular and hepatoid components showed the gastric phenotype, and the neuroendocrine component showed the mixed type. The unique composite tumor predominantly showed the gastric phenotype, and the hepatoid and neuroendocrine components were considered to be differentiated from the tubular component.

Association of Hospital Costs With Complications Following Total Gastrectomy for Gastric Adenocarcinoma.

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Selby, Luke V; Gennarelli, Renee L; Schnorr, Geoffrey C; Solomon, Stephen B; Schattner, Mark A; Elkin, Elena B; Bach, Peter B; Strong, Vivian E

2017-10-01

Postoperative complications are associated with increased hospital costs following major surgery, but the mechanism by which they increase cost and the categories of care that drive this increase are poorly described. To describe the association of postoperative complications with hospital costs following total gastrectomy for gastric adenocarcinoma. This retrospective analysis of a prospectively collected gastric cancer surgery database at a single National Cancer Institute-designated comprehensive cancer center included all patients undergoing curative-intent total gastrectomy for gastric adenocarcinoma between January 2009 and December 2012 and was conducted in 2015 and 2016. Ninety-day normalized postoperative costs. Hospital accounting system costs were normalized to reflect Medicare reimbursement levels using the ratio of hospital costs to Medicare reimbursement and categorized into major cost categories. Differences between costs in Medicare proportional dollars (MP $) can be interpreted as the amount that would be reimbursed to an average hospital by Medicare if it paid differentially based on types and extent of postoperative complications. In total, 120 patients underwent curative-intent total gastrectomy for stage I through III gastric adenocarcinoma between 2009 and 2012. Of these, 79 patients (65.8%) were men, and the median (interquartile range) age was 64 (52-70) years. The 51 patients (42.5%) who underwent an uncomplicated total gastrectomy had a mean (SD) normalized cost of MP $12 330 (MP $2500), predominantly owing to the cost of surgical care (mean [SD] cost, MP $6830 [MP $1600]). The 34 patients (28.3%) who had a major complication had a mean (SD) normalized cost of MP $37 700 (MP $28 090). Surgical care was more expensive in these patients (mean [SD] cost, MP $8970 [MP $2750]) but was a smaller contributor to total cost (24%) owing to increased costs from room and board (mean [SD] cost, MP $11 940 [MP $8820]), consultations (mean [SD

Oxygenated hemoglobin diffuse reflectance ratio for in vitro detection of human gastric pre-cancer

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Li, L. Q.; Wei, H. J.; Guo, Z. Y.; Yang, H. Q.; Wu, G. Y.; Xie, S. S.; Zhong, H. Q.; Li, X. Y.; Zhao, Q. L.; Guo, X.

2010-07-01

Oxygenated hemoglobin diffuse reflectance (DR) ratio (R540/R575) method based on DR spectral signatures is used for early diagnosis of malignant lesions of human gastric epithelial tissues in vitro. The DR spectra for four different kinds of gastric epithelial tissues were measured using a spectrometer with an integrating sphere detector in the spectral range from 400 to 650 nm. The results of measurement showed that the average DR spectral intensity for the epithelial tissues of normal stomach is higher than that for the epithelial tissues of chronic and malignant stomach and that for the epithelial tissues of chronic gastric ulcer is higher than that for the epithelial tissues of malignant stomach. The average DR spectra for four different kinds of gastric epithelial tissues show dips at 542 and 577 nm owing to absorption from oxygenated Hemoglobin (HbO2). The differences in the mean R540/R575 ratios of HbO2 bands are 6.84% between the epithelial tissues of normal stomach and chronic gastric ulcer, 14.7% between the epithelial tissues of normal stomach and poorly differentiated gastric adenocarcinoma and 22.6% between the epithelial tissues of normal stomach and undifferentiated gastric adenocarcinoma. It is evident from results that there were significant differences in the mean R540/R575 ratios of HbO2 bands for four different kinds of gastric epithelial tissues in vitro ( P < 0.01).

The Unusual Presentation of Gastric Adenocarcinoma as a Testicular Mass: A Favorable Response to Docetaxel and Cisplatin Plus Oral Tegafur/Uracil and Leucovorin

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Kai-Chung Yang

2010-02-01

Full Text Available Gastric cancer is one of the most common malignancies in the world. The routes of metastasis include direct extension, lymphatics, and peritoneal or hematogenous spread. Testicular metastasis is rare. We present here a 23-year-old gastric cancer patient who first presented with right-side testis swelling and pain. Diagnosis of metastatic adenocarcinoma was made after right-side orchiectomy. Gastric adenocarcinoma with ascites and peritoneal seeding was found after esophagogastroscopy and abdominal computed tomography. The patient received chemotherapy consisting of docetaxel 36 mg/m2 and cisplatin 30 mg/m2 on day 1 and day 8, plus oral tegafur/uracil 300 mg/m2/day and leucovorin 90 mg/day on day 1 to day 14 in a 21-day cycle, and he had a partial response to the chemotherapy. Metastatic tumors, especially gastric adenocarcinoma, should be considered in the differential diagnosis of patients presenting with testicular mass and they may respond well to chemotherapy.

Hearing loss as an unusual consequence of metastatic gastric adenocarcinoma

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CE Owers

2010-10-01

Full Text Available A sixty-one year old man was referred with a history of progressive dysphagia, vomiting and weight loss with some back pain. Upper gastrointestinal endoscopy and biopsies revealed a gastro-oesophageal junction adenocarcinoma. Despite the absence of metastatic disease on computed tomography, positron emission tomography demonstrated multiple vertebral and sternal deposits. He was reviewed in an ENT clinic with a sudden onset of hearing loss accompanied by dizziness, but no focal neurology. Magnetic resonance imaging identified bilateral 2cm lesions at the internal auditory meatus, consistent with a diagnosis of bilateral acoustic neuromas. The patient subsequently died of carcinomatosis and, because of the potential familial significance of bilateral acoustic neuromas, a limited post-mortem examination was carried out. Unexpectedly, this revealed bilateral adenocarcinoma metastases infiltrating the internal auditory meatus affecting the acoustic nerves. The authors believe this a very rare presentation of metastatic gastric disease.

Protective Effects of Female Reproductive Factors on Lauren Intestinal-Type Gastric Adenocarcinoma.

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Kim, Su Mi; Min, Byung Hoon; Lee, Jeeyun; An, Ji Yeong; Lee, Jun Ho; Sohn, Tae Sung; Bae, Jae Moon; Kim, Jae J; Kang, Won Ki; Kim, Sung; Choi, Min Gew

2018-01-01

Gastric cancer shows a male predominance that might be explained by protective effects from estrogens in females. Two Lauren classification histological subtypes, intestinal and diffuse, have distinct carcinogeneses. The purpose of this study was to estimate the effects of sex hormone on female gastric cancer according to Lauren classification. We reviewed medical records for and administered questionnaires, surveying reproductive and hormonal factors, to 758 patients who underwent gastrectomy for gastric cancer at Samsung Medical Center from May 2012 to November 2014. Clinicopathological characteristics were compared between females and males. The incidence of intestinal-type gastric cancer was compared between females subgroups, consist of premenopausal women and three groups of postmenopausal women (five-year intervals after menopause), and males. The association between reproductive factors and intestinal-type gastric cancer was analyzed by multivariate models for the female group. In total, 227 females (29.9%) and 531 males (70.9%) were included in the analysis. Undifferentiated adenocarcinoma and diffuse-type histology were more frequent in female patients than male patients. While 221 (41.6%) male patients had intestinal-type gastric cancer, no premenopausal female patient had this type of gastric cancer. The incidence of intestinal-type gastric cancer increased with time after menopause, and was similar to males after 10 years from menopause. Parity was associated with an increased risk of intestinal-type gastric cancer in menopausal women. These findings support that female sex hormones might be protective against intestinal-type gastric cancer. © Copyright: Yonsei University College of Medicine 2018

Carcinomatous meningitis due to gastric adenocarcinoma:A rare presentation of relapse

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Nibal; Saad; Ahmad; Alsibai; Tarik; H; Hadid

2014-01-01

While solid tumors are less commonly associated with meningeal involvement; lung, breast and melanoma are the ones most often reported. A few case reports have included gastric carcinoma but these are rare and most often associated with systemic disease at the time of diagnosis. Here we report a unique presentation of gastric carcinoma relapse with leptomeningeal carcinomatosis. An 81-year-old female was diagnosed with gastric cancer approximately one year before presentation. Following neoadjuvant chemotherapy, she had gastrectomy. Her periodic surveillance was stable. Thereafter she presented with a one week history of progressive fatigue lightheadedness, syncope. During hospitalization her mental status deteriorated. A repeat computed axial tomography scan of the head showed no changes to suggest an etiology. A lumbar puncture was performed and cerebral spinal fluid(CSF) cytopathology confirmed gastric signet cell adenocarcinoma. Encephalopathy was likely caused by increased intracranial pressure from communicating hydrocephalus.Leptomeningeal carcinomatosis is associated with short life expectancy. Therapeutic lumbar punctures and best supportive care or systemic therapy can be applied with guarded prognosis. Survival, however, may improve with cytologic negative conversion of the CSF if patient performance status allows treatment.

Técnica de la linfadenectomía estándar en el adenocarcinoma gástrico Standard lymphadenectomy technique in the gastric adenocarcinoma

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Roberto Eduardo Aguirre Fernández

2012-03-01

Full Text Available Se describe la técnica quirúrgica que se utiliza desde 1990 en el Hospital Provincial Clinicoquirúrgico Docente "Celia Sánchez Manduley", en Manzanillo, Granma, para realizar la gastrectomía junto a la linfadenectomia estándar, en los pacientes portadores de adenocarcinoma gástrico, la cual permite aplicar los conceptos oncológicos y quirúrgicos actuales de la Sociedad Japonesa para la Investigación del Cáncer Gástrico, imprescindibles para obtener un mejor pronóstico en estos pacientes.The surgical technique used from 1990 in the "Celia Sánchez Manduley" Clinical Surgical Teaching Provincial Hospital in Manzanillo, Gramma province to carry out the gastrectomy together with the standard lymphadenectomy in patients carriers of a gastric adenocarcinoma, allowing application of the current oncologic and surgical concepts of the Japanese Society for Research of Gastric Cancer, essential to obtain a better prognosis in these patients.

Comparison of histological and molecular diagnosis of Helicobacter pylori in benign lesions and gastric adenocarcinoma Comparação dos diagnósticos histológico e molecular do Helicobacter pylori em lesões benignas e adenocarcinomas gástricos

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Ana Cristina Gobbo César

2005-03-01

Full Text Available Helicobacter pylori colonization is associated with chronic gastritis, peptic ulcers, intestinal metaplasia, adenocarcinoma and lymphoma of the stomach. The objective of this study was to compare the results of the routinely used histology with molecular diagnosis for the detection of H. pylori. Eighty samples from gastric lesions (chronic gastritis, atrophic gastritis, gastric ulcer, and intestinal metaplasia, 18 gastric adenocarcinoma and 10 normal mucosa H. pylori-negative (control samples were obtained. All samples were examined histologically (hematoxylin-eosin and Giemsa staining, and PCR amplifications of the species-specific antigen gene (H3H4 and urease A gene segment (H5H6 of H. pylori were made, using the human gene CYP1A1 for DNA quality control. In the benign lesion and adenocarcinoma the infection was detected in 43% (42/98 and 71% (70/98 by histological and molecular diagnosis (p = 0.0001, respectively. The PCR test detected H. pylori in 27.5% (22/80 of the benign gastric lesions and in 50% (9/18 of the gastric adenocarcinoma cases, the histological diagnosis being negative for this bacterium. About 2.5% of the samples, exclusively from benign lesions and with a positive histological diagnosis, showed negative molecular results for both primers. Statistically significant differences were found between the histological and the molecular method in intestinal metaplasia (p = 0.0461 and gastric adenocarcinoma (p = 0.0011, due to underdetection of H. pylori by the histological method, which is probably due to the low density of the bacterium as a consequence of the severe atrophy of the gastric mucosa. Our findings suggest that PCR is the more efficient method for the assessment of H. pylori infection, especially in metaplasia and gastric adenocarcinoma.A colonização do Helicobacter pylori está associada com gastrite crônica, úlcera péptica, metaplasia intestinal, adenocarcinoma e linfoma gástrico. O objetivo desse estudo foi

Epigenetic subgroups of esophageal and gastric adenocarcinoma with differential GATA5 DNA methylation associated with clinical and lifestyle factors.

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Xinhui Wang

Full Text Available BACKGROUND: Adenocarcinomas located near the gastroesophageal junction have unclear etiology and are difficult to classify. We used DNA methylation analysis to identify subtype-specific markers and new subgroups of gastroesophageal adenocarcinomas, and studied their association with epidemiological risk factors and clinical outcomes. METHODOLOGY/PRINCIPAL FINDINGS: We used logistic regression models and unsupervised hierarchical cluster analysis of 74 DNA methylation markers on 45 tumor samples (44 patients of esophageal and gastric adenocarcinomas obtained from a population-based case-control study to uncover epigenetic markers and cluster groups of gastroesophageal adenocarcinomas. No distinct epigenetic differences were evident between subtypes of gastric and esophageal cancers. However, we identified two gastroesophageal adenocarcinoma subclusters based on DNA methylation profiles. Group membership was best predicted by GATA5 DNA methylation status. We analyzed the associations between these two epigenetic groups and exposure using logistic regression, and the associations with survival time using Cox regression in a larger set of 317 tumor samples (278 patients. There were more males with esophageal and gastric cardia cancers in Cluster Group 1 characterized by higher GATA5 DNA methylation values (all p<0.05. This group also showed associations of borderline statistical significance with having ever smoked (p-value = 0.07, high body mass index (p-value = 0.06, and symptoms of gastroesophageal reflux (p-value = 0.07. Subjects in cluster Group 1 showed better survival than those in Group 2 after adjusting for tumor differentiation grade, but this was not found to be independent of tumor stage. CONCLUSIONS/SIGNIFICANCE: DNA methylation profiling can be used in population-based studies to identify epigenetic subclasses of gastroesophageal adenocarcinomas and class-specific DNA methylation markers that can be linked to

Intensity-Modulated Radiation Therapy With Concurrent Chemotherapy as Preoperative Treatment for Localized Gastric Adenocarcinoma

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Chakravarty, Twisha; Crane, Christopher H. [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX (United States); Ajani, Jaffer A. [Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX (United States); Mansfield, Paul F. [Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX (United States); Briere, Tina M.; Beddar, A. Sam [Department of Radiation Physics, University of Texas MD Anderson Cancer Center, Houston, TX (United States); Mok, Henry; Reed, Valerie K.; Krishnan, Sunil; Delclos, Marc E. [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX (United States); Das, Prajnan, E-mail: PrajDas@mdanderson.org [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX (United States)

2012-06-01

Purpose: The goal of this study was to evaluate dosimetric parameters, acute toxicity, pathologic response, and local control in patients treated with preoperative intensity-modulated radiation therapy (IMRT) and concurrent chemotherapy for localized gastric adenocarcinoma. Methods: Between November 2007 and April 2010, 25 patients with localized gastric adenocarcinoma were treated with induction chemotherapy, followed by preoperative IMRT and concurrent chemotherapy and, finally, surgical resection. The median radiation therapy dose was 45 Gy. Concurrent chemotherapy was 5-fluorouracil and oxaliplatin in 18 patients, capecitabine in 3, and other regimens in 4. Subsequently, resection was performed with total gastrectomy in 13 patients, subtotal gastrectomy in 7, and other surgeries in 5. Results: Target coverage, expressed as the ratio of the minimum dose received by 99% of the planning target volume to the prescribed dose, was a median of 0.97 (range, 0.92-1.01). The median V{sub 30} (percentage of volume receiving at least 30 Gy) for the liver was 26%; the median V{sub 20} (percentage of volume receiving at least 20 Gy) for the right and left kidneys was 14% and 24%, respectively; and the median V{sub 40} (percentage of volume receiving at least 40 Gy) for the heart was 18%. Grade 3 acute toxicity developed in 14 patients (56%), including dehydration in 10, nausea in 8, and anorexia in 5. Grade 4 acute toxicity did not develop in any patient. There were no significant differences in the rates of acute toxicity, hospitalization, or feeding tube use in comparison to those in a group of 50 patients treated with preoperative three-dimensional conformal radiation therapy with concurrent chemotherapy. R0 resection was obtained in 20 patients (80%), and pathologic complete response occurred in 5 (20%). Conclusions: Preoperative IMRT for gastric adenocarcinoma was well tolerated, accomplished excellent target coverage and normal structure sparing, and led to appropriate

Intensity-Modulated Radiation Therapy With Concurrent Chemotherapy as Preoperative Treatment for Localized Gastric Adenocarcinoma

International Nuclear Information System (INIS)

Chakravarty, Twisha; Crane, Christopher H.; Ajani, Jaffer A.; Mansfield, Paul F.; Briere, Tina M.; Beddar, A. Sam; Mok, Henry; Reed, Valerie K.; Krishnan, Sunil; Delclos, Marc E.; Das, Prajnan

2012-01-01

Purpose: The goal of this study was to evaluate dosimetric parameters, acute toxicity, pathologic response, and local control in patients treated with preoperative intensity-modulated radiation therapy (IMRT) and concurrent chemotherapy for localized gastric adenocarcinoma. Methods: Between November 2007 and April 2010, 25 patients with localized gastric adenocarcinoma were treated with induction chemotherapy, followed by preoperative IMRT and concurrent chemotherapy and, finally, surgical resection. The median radiation therapy dose was 45 Gy. Concurrent chemotherapy was 5-fluorouracil and oxaliplatin in 18 patients, capecitabine in 3, and other regimens in 4. Subsequently, resection was performed with total gastrectomy in 13 patients, subtotal gastrectomy in 7, and other surgeries in 5. Results: Target coverage, expressed as the ratio of the minimum dose received by 99% of the planning target volume to the prescribed dose, was a median of 0.97 (range, 0.92–1.01). The median V 30 (percentage of volume receiving at least 30 Gy) for the liver was 26%; the median V 20 (percentage of volume receiving at least 20 Gy) for the right and left kidneys was 14% and 24%, respectively; and the median V 40 (percentage of volume receiving at least 40 Gy) for the heart was 18%. Grade 3 acute toxicity developed in 14 patients (56%), including dehydration in 10, nausea in 8, and anorexia in 5. Grade 4 acute toxicity did not develop in any patient. There were no significant differences in the rates of acute toxicity, hospitalization, or feeding tube use in comparison to those in a group of 50 patients treated with preoperative three-dimensional conformal radiation therapy with concurrent chemotherapy. R0 resection was obtained in 20 patients (80%), and pathologic complete response occurred in 5 (20%). Conclusions: Preoperative IMRT for gastric adenocarcinoma was well tolerated, accomplished excellent target coverage and normal structure sparing, and led to appropriate pathologic

64Cu DOTA-Trastuzumab PET/CT in Studying Patients With Gastric Cancer

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2017-12-11

Adenocarcinoma of the Gastroesophageal Junction; Diffuse Adenocarcinoma of the Stomach; Intestinal Adenocarcinoma of the Stomach; Mixed Adenocarcinoma of the Stomach; Recurrent Gastric Cancer; Stage IA Gastric Cancer; Stage IB Gastric Cancer; Stage IIA Gastric Cancer; Stage IIB Gastric Cancer; Stage IIIA Gastric Cancer; Stage IIIB Gastric Cancer; Stage IIIC Gastric Cancer; Stage IV Gastric Cancer

Laparoscopic gastrectomy for gastric adenocarcinoma: Long-term results Gastrectomía laparoscópica por adenocarcinoma gástrico: Resultados a largo plazo

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F. J. Ibáñez Aguirre

2006-06-01

Full Text Available Background: the objective of our paper is to report on the long-term results of patients with gastric cancer treated by mini-invasive surgery with "intention-to-treat" laparoscopy. Patients and methods: between June 1993 and January 2006, 130 patients comprising 94 men and 36 women with gastric adenocarcinoma were prospectively selected by two surgical teams in three hospitals based on a prior agreement (CHU Charleroi, Belgium, Centre Hospitalier de Luxembourg and Zumárraga Hospital, Spain. Patients with adenocarcinoma of the cardia were excluded. Mean age of patients was 68 years (range, 37-85 years. Results: post-operative mortality within 60 days of operation was 6 patients; 109 patients were therefore properly followed up for an average of 49 months (range, 2-153 months. Average survival time for 10 non-resected patients was 4.5 months. Average survival rate for all 14 palliatively resected patients was 6.9 months. Actuarial 5-year survival rate for R0-type surgery was 35%. Global actuarial 5-year survival rate after resective surgery was 31%. Conclusions: laparoscopic gastrectomy with any kind of lymphadenectomy is a major but safe operation with acceptable mortality and morbility rates in patients with advanced gastric cancer, usually in poor general condition. Laparoscopic gastrectomy for locally advanced cancers is equivalent to laparotomy as far as long-term oncological results are concerned.

A Rare Association of Autoimmune Hemolytic Anemia with Gastric Adenocarcinoma

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Kavita Agrawal

2017-01-01

Full Text Available An 80-year-old male presented with dyspnea on exertion for at least two months. He also complained of progressive dysphagia and weight loss of 35 pounds over the last eight months. Initial blood tests showed hemoglobin of 6.1 g/dl, reticulocytes count of 19.7%, total bilirubin of 3.2 mg/dl, lactate dehydrogenase of 600 U/L, and haptoglobin of less than 8 mg/dl, and direct Coombs test was positive for warm immunoglobulin G. The impression was autoimmune hemolytic anemia (AIHA. The evaluation of dysphagia with esophagogastroduodenoscopy revealed a single irregular 4 cm malignant appearing ulcerated mass at the incisura angularis of the stomach. The mass was confirmed as adenocarcinoma on biopsy. Diagnostic laparoscopy was positive for malignant cells and he was diagnosed with stage IV adenocarcinoma of the stomach. Other extensive workup to determine the etiology of AIHA was negative (described in detail below. Surgery was deferred primarily due to metastasis of cancer. Initially, hemoglobin was stabilized by intravenous methylprednisolone, high dose immunoglobulins, and packed red blood cell transfusions. After a few weeks, hemoglobin started trending down again. The patient was weaned off steroids and paradoxically IgG-mediated autohemolysis was controlled with the initiation of palliative chemotherapy. Our case highlights a rare occurrence of AIHA in association with gastric adenocarcinoma.

Prevalence of Helicobacter Pylori in Gastric Fluid in the Surgical Patient

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Mc

1998-01-01

Helicobacter pylori is a bacterium that infects the human gastric mucosa. It is well established as a primary factor in peptic ulcer disease and has been implicated in the pathogenesis of gastric adenocarcinoma...

Small bowel adenocarcinoma copy number profiles are more closely related to colorectal than to gastric cancers

NARCIS (Netherlands)

Haan, J.C.; Buffart, T.E.; Eijk, P.P.; van de Wiel, M.A.; van Wieringen, W.N.; Howdle, P.D.; Mulder, C.J.J.; van de Velde, CJ; Quirke, P.; Nagtegaal, I.D.; van Grieken, N.C.T.; Grabsch, H.; Meijer, G.A.; Ylstra, B.

2012-01-01

Background: Small bowel adenocarcinoma (SBA) is a rare cancer and consequently, the options for clinical trials are limited. As they are treated according to either a colorectal or a gastric cancer regimen and the molecular biology of a tumor is a pivotal determinant for therapy response,

Small bowel adenocarcinoma copy number profiles are more closely related to colorectal than to gastric cancers.

NARCIS (Netherlands)

Haan, J.C.; Buffart, T.E.; Eijk, P.P.; Wiel, M.A. van de; Wieringen, W.N. van; Howdle, P.D.; Mulder, C.J.; Velde, C.J. van de; Quirke, P.; Nagtegaal, I.D.; Grieken, N.C. van; Grabsch, H.; Meijer, G.A.; Ylstra, B.

2012-01-01

BACKGROUND: Small bowel adenocarcinoma (SBA) is a rare cancer and consequently, the options for clinical trials are limited. As they are treated according to either a colorectal or a gastric cancer regimen and the molecular biology of a tumor is a pivotal determinant for therapy response,

Is there any advantage to combined trastuzumab and chemotherapy in perioperative setting her 2neu positive localized gastric adenocarcinoma?

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Albouzidi Abderrahmane

2011-09-01

Full Text Available Abstract We report here a 44-year-old Moroccan man with resectable gastric adenocarcinoma with overexpression of human epidermal growth factor receptor 2 (HER2 by immunohistochemistry who was treated with trastuzumab in combination with chemotherapy in perioperative setting. He received 3 cycles of neoadjuvant chemotherapy consisting of trastuzumab, oxaliplatin, and capecitabine. Afterwards, he received total gastrectomy with extended D2 lymphadenectomy without spleno-pancreatectomy. A pathologic complete response was obtained with a combination of trastuzumab and oxaliplatin and capecitabine. He received 3 more cycles of trastuzumab containing regimen postoperatively. We conclude that resectable gastric carcinoma with overexpression of the c-erbB-2 protein should ideally be managed with perioperative combination of trastuzumab with chemotherapy. Further research to evaluate trastuzumab in combination with chemotherapy regimens in the perioperative and adjuvant setting is urgently needed.

Association of visceral adiposity with oesophageal and junctional adenocarcinomas.

LENUS (Irish Health Repository)

Beddy, P

2012-02-01

BACKGROUND: Obesity is associated with an increased incidence of oesophageal and oesophagogastric junction adenocarcinoma, in particular Siewert types I and II. This study compared abdominal fat composition in patients with oesophageal\\/junctional adenocarcinoma with that in patients with oesophageal squamous cell carcinoma and gastric adenocarcinoma, and in controls. METHOD: In total, 194 patients (110 with oesophageal\\/junctional adenocarcinoma, 38 with gastric adenocarcinoma and 46 with oesophageal squamous cell carcinoma) and 90 matched control subjects were recruited. The abdominal fat area was assessed using computed tomography (CT), and the total fat area (TFA), visceral fat area (VFA) and subcutaneous fat area (SFA) were calculated. RESULTS: Patients with oesophageal\\/junctional adenocarcinoma had significantly higher TFA and VFA values compared with controls (both P < 0.001), patients with gastric adenocarcinoma (P = 0.013 and P = 0.006 respectively) and patients with oesophageal squamous cell carcinoma (both P < 0.001). For junctional tumours, the highest TFA and VFA values were seen in patients with Siewert type I tumours (respectively P = 0.041 and P = 0.033 versus type III; P = 0.332 and P = 0.152 versus type II). CONCLUSION: Patients with oesophageal\\/junctional adenocarcinoma, in particular oesophageal and Siewert type I junctional tumours, have greater CT-defined visceral adiposity than patients with gastric adenocarcinoma or oesophageal squamous cell carcinoma, or controls.

Intraoperative Radiotherapy Combined With Adjuvant Chemoradiotherapy for Locally Advanced Gastric Adenocarcinoma

International Nuclear Information System (INIS)

Fu Shen; Lu Jiade; Zhang Qing; Yang Zhe; Peng Lihua; Xiong, Fei

2008-01-01

Purpose: To evaluate the efficacy of intraoperative radiotherapy (IORT) followed by concurrent chemotherapy and external beam RT (EBRT) in the treatment of locally advanced gastric adenocarcinoma. Methods and Materials: A total of 97 consecutive and nonselected patients with newly diagnosed Stage T3, T4, or N+ adenocarcinoma of the stomach underwent gastrectomy with D2 lymph node dissection between March 2003 and October 2005. Of the 97 patients, 51 received adjuvant concurrent chemotherapy (5-fluorouracil, leucovorin, docetaxel, and cisplatin) and EBRT (EBRT group) and 46 received IORT (dose range, 12-15 Gy) immediately after gastrectomy and lymph node dissection before concurrent chemoradiotherapy (EBRT+IORT group). Results: After a median follow-up of 24 months, the 3-year locoregional control rate was 77% and 63% in the two groups with or without IORT, respectively (p = 0.05). The 3-year overall survival and disease-free survival rate was 47% and 36% in the EBRT group and 56% and 44% in the EBRT+IORT group, respectively (p > 0.05). Multivariate analyses revealed that the use of IORT, presence of residual disease after surgery, and pN category were independent prognostic factors for locoregional control and that IORT, pN, and pT categories were independent prognostic factors for overall survival (p < 0.05). Four patients experienced Grade 3 or 4 late complications, but no significant difference was observed between the two groups. Conclusions: Radical gastrectomy with D2 lymph node dissection and IORT followed by adjuvant chemoradiotherapy appeared to be feasible and well-tolerated in the treatment of locally advanced gastric cancer. The addition of IORT to the trimodality treatment significantly improved the 3-year locoregional control rate

Identification of the intestinal type gastric adenocarcinoma transcriptomic markers using bioinformatic and gene expression analysis

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V. V. Volkomorov

2017-01-01

Full Text Available Introduction. Searching for specific and sensitive molecular tumor markers is one of the important tasks of modern oncology. These markers can be used for early tumor diagnosis and prognosis as well as for prediction of therapeutic response, estimation of tumor volume or to assess disease recurrence through monitoring. Gene expression data base mining followed by experimental validation of results obtained is one of the promising approaches for searching of that kind.Objective: to identify several membrane proteins which can be used for serum diagnosis of intestinal type of gastric adenocarcinoma.Materials and methods. We used bioinformatic-driven search using Gene Ontology and The Cancer Genome Atlas (TCGA data to identify mRNA up-regulated in gastric cancer (GC. Then, the expression levels of the mRNAs in 55 pare clinical specimens were investigated using reverse transcription polymerase chain reaction.Results. Comparative analysis of the mRNA levels in normal and tumor tissues using a new bioinformatics algorithm allowed to identify 3 high-copy transcripts (SULF1, PMEPA1 and SPARC, intracellular content of which markedly increased in GC. Expression analysis of these genes in clinical specimens showed significantly higher mRNA levels of PMEPA1 and SPARC in tumor as compared to normal gastric tissue. Interestingly more than twofold increase in expression level of these genes was observed in 75 % of intestinal-type GC. The same results were found only in 25 and 38 % of diffuse-type GC respectively.Conclusions. As a result of original bioinforamtic analysis using TCGA data base two genes (PMEPA1 and SPARC were shown to be significantly upregulated in intestinal-type gastric adenocarcinoma. The findings show the importance of further investigation to clarify the clinical value of their expression level in stomach tumors as well as their role in carcinogenesis.

Synchronous Gastric Gastrointestinal Stromal Tumor and Colon Adenocarcinoma: A Case Report

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Thivi Vasilakaki

2014-01-01

Full Text Available Gastrointestinal stromal tumors (GISTs represent the majority of primary mesenchymal tumors of the gastrointestinal tract. They are generally considered to be solitary tumors and therefore the synchronous occurrence with other primary malignancies of gastrointestinal track is considered a rare event. Here we present the case of a 75-year-old man admitted to our hospital with a 10-day history of gastrointestinal bleeding. Colonoscopy revealed an ulcerative mass of 4 cm in diameter in the ascending colon. Gastroscopy revealed a bulge in the gastric body measuring 1 cm in diameter with normal overlying mucosa. Surgical intervention was suggested and ileohemicolectomy with regional lymph node resection along with gastric wedge resection was performed. Pathologic examination of the ascending colon mass showed an invasive moderately differentiated adenocarcinoma stage III B (T3N1M0. Grossly resected wedge of stomach showed a well circumscribed intramural tumor which microscopically was consistent with essentially benign gastrointestinal stromal tumor (according to Miettinen criteria. The patient did not receive additional treatment. Two years later the patient showed no evidence of recurrence or metastasis.

Multicenter phase II study of irinotecan, cisplatin, and bevacizumab in patients with metastatic gastric or gastroesophageal junction adenocarcinoma.

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Shah, Manish A; Ramanathan, Ramesh K; Ilson, David H; Levnor, Alissa; D'Adamo, David; O'Reilly, Eileen; Tse, Archie; Trocola, Robin; Schwartz, Lawrence; Capanu, Marinela; Schwartz, Gary K; Kelsen, David P

2006-11-20

Bevacizumab improves survival in several solid tumor malignancies when combined with chemotherapy. We evaluated the efficacy and safety of the addition of bevacizumab to chemotherapy in the treatment of gastric and gastroesophageal junction (GEJ) adenocarcinoma. Forty-seven patients with metastatic or unresectable gastric/GEJ adenocarcinoma were treated with bevacizumab 15 mg/kg on day 1, irinotecan 65 mg/m2, and cisplatin 30 mg/m2 on days 1 and 8, every 21 days. The primary end point was to demonstrate a 50% improvement in time to progression over historical values. Secondary end points included safety, response, and survival. Patient characteristics were as follows: median age 59 years (range, 25 to 75); Karnofsky performance status 90% (70% to 100%); male:female, 34:13; and gastric/GEJ, 24:23. With a median follow-up of 12.2 months, median time to progression was 8.3 months (95% CI, 5.5 to 9.9 months). In 34 patients with measurable disease, the overall response rate was 65% (95% CI, 46% to 80%). Median survival was 12.3 months (95% CI, 11.3 to 17.2 months). We observed no increase in chemotherapy related toxicity. Possible bevacizumab-related toxicity included a 28% incidence of grade 3 hypertension, two patients with a gastric perforation and one patient with a near perforation (6%), and one patient with a myocardial infarction (2%). Grade 3 to 4 thromboembolic events occurred in 25% of patients. Although the primary tumor was unresected in 40 patients, we observed only one patient with a significant upper gastrointestinal bleed. Bevacizumab can be safely given with chemotherapy even with primary gastric and GEJ tumors in place. The response rate, time to disease progression (TTP), and overall survival are encouraging, with TTP improved over historical controls by 75%. Further development of bevacizumab in gastric and GEJ cancers is warranted.

Interrelationship between chromosome 8 aneuploidy, C-MYC amplification and increased expression in individuals from northern Brazil with gastric adenocarcinoma

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Calcagno, Danielle Queiroz; Leal, Mariana Ferreira; Seabra, Aline Damaceno; Khayat, André Salim; Chen, Elizabeth Suchi; Demachki, Samia; Assumpção, Paulo Pimentel; Faria, Mario Henrique Girão; Rabenhorst, Silvia Helena Barem; Ferreira, Márcia Valéria Pitombeira; Smith, Marília de Arruda Cardoso; Burbano, Rommel Rodríguez

2006-01-01

AIM: To investigate chromosome 8 numerical aberrations, C-MYC oncogene alterations and its expression in gastric cancer and to correlate these findings with histopathological characteristics of gastric tumors. METHODS: Specimens were collected surgically from seven patients with gastric adenocarcinomas. Immunostaining for C-MYC and dual-color fluorescence in situ hybridization (FISH) for C-MYC gene and chromosome 8 centromere were performed. RESULTS: All the cases showed chromosome 8 aneuploidy and C-MYC amplification, in both the diffuse and intestinal histopathological types of Lauren. No significant difference (P < 0.05) was observed between the level of chromosome 8 ploidy and the site, stage or histological type of the adenocarcinomas. C-MYC high amplification, like homogeneously stained regions (HSRs) and double minutes (DMs), was observed only in the intestinal-type. Structural rearrangement of C-MYC, like translocation, was observed only in the diffuse type. Regarding C-MYC gene, a significant difference (P < 0.05) was observed between the two histological types. The C-MYC protein was expressed in all the studied cases. In the intestinal-type the C-MYC immunoreactivity was localized only in the nucleus and in the diffuse type in the nucleus and cytoplasm. CONCLUSION: Distinct patterns of alterations between intestinal and diffuse types of gastric tumors support the hypothesis that these types follow different genetic pathways. PMID:17036397

EGFR and AKT1 overexpression are mutually exclusive and associated with a poor survival in resected gastric adenocarcinomas.

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Petrini, Iacopo; Lencioni, Monica; Vasile, Enrico; Fornaro, Lorenzo; Belluomini, Lorenzo; Pasquini, Giulia; Ginocchi, Laura; Caparello, Chiara; Musettini, Gianna; Vivaldi, Caterina; Caponi, Sara; Ricci, Sergio; Proietti, Agenese; Fontanini, Gabriella; Naccarato, Antonio Giuseppe; Nardini, Vincenzo; Santi, Stefano; Falcone, Alfredo

2018-02-14

The evaluation of molecular targets in gastric cancer has demonstrated the predictive role of HER2 amplification for trastuzumab treatment in metastatic gastric cancer. Besides HER2, other molecular targets are under evaluation in metastatic gastric tumors. However, very little is known about their role in resected tumors. We evaluated the expression of HER2, EGFR, MET, AKT1 and phospho-mTOR in resected stage II-III adenocarcinomas. Ninety-two patients with resected stomach (63%) or gastro-esophageal adenocarcinomas (27%) were evaluated. Antibodies anti-HER2, EGFR, MET, AKT1 and phospho-mTOR were used for immunostaining of formalin-fixed paraffin-embedded slides. Using FISH, HER2 amplification was evaluated in cases with an intermediate (+2) staining. EGFR overexpression (11%) was a poor prognostic factor for overall survival (3-year OS: 47% vs 77%; Log-Rank p= 0.033). MET overexpression (36%) was associated with a trend for a worse survival (3-year OS: 65% vs 77%; Log-Rank p= 0.084). HER2 amplification/overexpression and mTOR hyper-phosphorylation were observed in 13% and 48% of tumors, respectively. AKT1 overexpression (8%) was not a prognostic factor by itself (p= 0.234). AKT1 and EGFR overexpression was mutually exclusive and patients with EGFR or AKT1 overexpression experienced a poor prognosis (3-year OS: 52% vs. 79%, Log-Rank p= 0.005). EGFR is confirmed a poor prognostic factor in resected gastric cancers. We firstly describe a mutually exclusive overexpression of EGFR and AKT1 with potential prognostic implications, suggesting the relevance of this pathway for the growth of gastric cancers.

Mucin phenotypic expression and p53 gene abnormality of gastric super-minute well-differentiated adenocarcinoma: Re-evaluation with relationship between histogenesis of well-differentiated adenocarcinoma and intestinal metaplasia in distal stomach

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Yamaguchi Toshikazu

2005-01-01

Full Text Available Abstract Background Although the gastric well-differentiated adenocarcinoma in the distal stomach has been thought to develop via a intestinal metaplasia-carcinoma sequence, there are some disproofs from new mucin examinations for minute-size lesions in same type carcinoma. The current study was performed and pointed out the new findings for the solution to the problem according to the point described above. Methods 12 super-minute lesions (less than 1 mm in maximum diameter of well-differentiated adenocarcinoma in distal stomach (SMCa, which were detected from the pathological examinations of 210 surgically resected stomach specimens, and the mucosa adjacent to these carcinoma lesions, were examined by immunohistochemical mucin stainings (MUC2 and CD-10: intestinal phenotype, 45M1 and MUC6: gastric phenotype and p53-overexpression. And the analyses of the replication error of the microsatellites in chromosome 17 related p53 gene (TP53 and D17S786 (RER-p53MS were performed in SMCa lesions, adjacent mucosa to each lesion and other gastric mucosa with intestinal metaplasia, because all SMCa lesions showed p53-overexpression immunohistochemically, decribed below. Results 1. The carcinoma cells in all SMCa lesions were positive for 45M1 and p53. On the other hand, no positive carcinoma cells for MUC6 were seen although the pyloric glands and the remnant pyloric gland in the SMCa lesions in the same slides were positive for MUC6. Ten lesions (83% had intestinal phenotypic mucin (10 lesions: MUC2 (+, 4 lesions: CD10 (+. Two lesions (17% were positive for only 45M1 (gastric phenotypic mucin. 2. All of the mucosa adjacent to SMCa showed intestinal metaplasia (complete type: 7 regions, incomplete type: 5 regions. 3. RER-p53MS was confirmed in 42% (5/12 regions of SMCa, in 42% (5/12 regions of the mucosa adjacent to SMCa and 14% (6/42 regions of the other intestinal metaplasia mucosa. Conclusion Most of the super-minute well-differentiated adenocarcinoma

Diffuse-type Gastric Mucinous and Signet Ring Cell Adenocarcinoma in a Captive California King Snake (Lampropeltis getula californiae).

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Hsueh, C-S; Li, W-T; Jeng, C-R; Pang, V F; Chang, H-W

2018-04-01

An adult female California king snake (Lampropeltis getula californiae) housed in Taipei Zoo was presented with a 2-week history of anorexia, fatigue and abdominal swelling. Exploratory laparotomy revealed a gastric mass with two circular perforations and multiple mottled white to beige protuberances along the mucosal surface. Histologically, the gastric mass showed an invasive, transmural growth of epithelial cells arranged in nests, lobules, acini and sheets in the mucosa and submucosa that progressively transformed into signet ring cells in the muscularis externa and subserosa. All of the neoplastic cells expressed pan-cytokeratin immunohistochemically. Based on the World Health Organization histological criteria, a diagnosis of diffuse-type gastric mucinous and signet ring cell adenocarcinoma was made. Copyright © 2018 Elsevier Ltd. All rights reserved.

Impact of marital status on survival of gastric adenocarcinoma patients: Results from the Surveillance Epidemiology and End Results (SEER) Database.

Science.gov (United States)

Qiu, Miaozhen; Yang, Dajun; Xu, Ruihua

2016-02-15

Marital status was found to be an independent prognostic factor for survival in various cancer types. In this study, we used the Surveillance, Epidemiology and End Results database to analyze the survival difference among different marital status in the United States. Gastric adenocarcinoma patients from 2004-2012 were enrolled for study. The 5-year cause specific survival (CSS) was our primary endpoint. Totally 29,074 eligible patients were identified. We found that more male patients were married than female. Asian patients had the highest percentages of married than the other races. More married patients were covered by the insurance. Married patients had better 5-year CSS than unmarried, 30.6% vs 25.7%, P married and unmarried patients, hazard ratio: 1.09 (95% confidence interval: 1.01-1.17), P = 0.027. The survival difference was significant in the insured but not in the uninsured patients. Widowed patients had the worst prognosis compared with other groups even though they had more stage I disease and more well / moderate differentiated tumors. These results indicated that unmarried gastric adenocarcinoma patients were at greater risk of cancer specific mortality. We recommend every patient should have access to best available gastric cancer therapy.

[Gastric cancer detection using kubelka-Munk spectral function of DNA and protein absorption bands].

Science.gov (United States)

Li, Lan-quan; Wei, Hua-jiang; Guo, Zhou-yi; Yang, Hong-qin; Xie, Shu-sen; Chen, Xue-mei; Li, Li-bo; He, Bol-hua; Wu, Guo-yong; Lu, Jian-jun

2009-09-01

Differential diagnosis for epithelial tissues of normal human gastric, undifferentiation gastric adenocarcinoma, gastric squamous cell carcinomas, and poorly differentiated gastric adenocarcinoma were studied using the Kubelka-Munk spectral function of the DNA and protein absorption bands at 260 and 280 nm in vitro. Diffuse reflectance spectra of tissue were measured using a spectrophotometer with an integrating sphere attachment. The results of measurement showed that for the spectral range from 250 to 650 nm, pathological changes of gastric epithelial tissues induced that there were significant differences in the averaged value of the Kubelka-Munk function f(r infinity) and logarithmic Kubelka-Munk function log[f(r infinity)] of the DNA absorption bands at 260 nm between epithelial tissues of normal human stomach and human undifferentiation gastric cancer, between epithelial tissues of normal human stomach and human gastric squamous cell carcinomas, and between epithelial tissues of normal human stomach and human poorly differentiated cancer. Their differences were 68.5% (p function f(r infinity) and logarithmic Kubelka-Munk function log[f(r infinity)] of the protein absorption bands at 280 nm between epithelial tissues of normal human stomach and human undifferentiation gastric cancer, between epithelial tissues of normal human stomach and human gastric squamous cell carcinomas, and between epithelial tissues of normal human stomach and human poorly differentiated cancer. Their differences were 86.8% (p function f(r infinity) and logarithmic Kubelka-Munk function log[f(r infinity)] of the carotene absorption bands at 480 nm between epithelial tissues of normal human stomach and human undifferentiation gastric cancer, between epithelial tissues of normal human stomach and human gastric squamous cell carcinomas, and between epithelial tissues of normal human stomach and human poorly differentiated cancer. Their differences were 59.5% (p < 0.05), 73% (p < 0

Adenocarcinoma of the cervical esophagus arising in heterotopic gastric mucosa: exclusive chemoradiotherapy following a mucosal resection

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Jestin-Letallec, V.; Muller, M.; Metges, J.P.; Bouchekoua, M.; Albarghach, N.; Pradier, O. [Departement de Cancerologie, 29 - Brest (France)

2007-11-15

Esophagus adenocarcinomas developing within heterotopic gastric mucosa are very rare and described to be found endoscopically in a prevalence of .29%. We report a case of cervical adenocarcinoma arising in ectopic gastric mucosa in a fifty-four year old man. The patient underwent a mucosal resection followed with exclusive chemoradiotherapy because of infiltration of the sub mucosa layer. A radiotherapy dose of 60 Gy ( 2 Gy/Fr, 30 Fr) was realized with a reduction of the fields at 50 Gy associated with a continuous 5FU-cisplatin combination after eliminating known mutation in the dihydro-pyrimidine of the dehydrogenase gene. for this tumor, surgery is the main treatment, (oesophagectomy associated with laryngo-pharyngectomy) and has an important repercussion on the quality of life. Because of the refusal of our patient, after a mucosal resection attempt, we proposed our patient a chemoradiotherapy. For the first time in the literature, we report the results of radio chemotherapy for this rare tumor. Eighteen months after the treatment, the patient is alive without sign of recurrence. The radio chemotherapy could be a safety treatment for this rare tumor associated with a good quality of life. A review of the literature since 1950 will be shown. (authors)

Adenocarcinoma of the cervical esophagus arising in heterotopic gastric mucosa: exclusive chemoradiotherapy following a mucosal resection

International Nuclear Information System (INIS)

Jestin-Letallec, V.; Muller, M.; Metges, J.P.; Bouchekoua, M.; Albarghach, N.; Pradier, O.

2007-01-01

Esophagus adenocarcinomas developing within heterotopic gastric mucosa are very rare and described to be found endoscopically in a prevalence of .29%. We report a case of cervical adenocarcinoma arising in ectopic gastric mucosa in a fifty-four year old man. The patient underwent a mucosal resection followed with exclusive chemoradiotherapy because of infiltration of the sub mucosa layer. A radiotherapy dose of 60 Gy ( 2 Gy/Fr, 30 Fr) was realized with a reduction of the fields at 50 Gy associated with a continuous 5FU-cisplatin combination after eliminating known mutation in the dihydro-pyrimidine of the dehydrogenase gene. for this tumor, surgery is the main treatment, (oesophagectomy associated with laryngo-pharyngectomy) and has an important repercussion on the quality of life. Because of the refusal of our patient, after a mucosal resection attempt, we proposed our patient a chemoradiotherapy. For the first time in the literature, we report the results of radio chemotherapy for this rare tumor. Eighteen months after the treatment, the patient is alive without sign of recurrence. The radio chemotherapy could be a safety treatment for this rare tumor associated with a good quality of life. A review of the literature since 1950 will be shown. (authors)

Enterococcus faecalis Infection and Reactive Oxygen Species Down-Regulates the miR-17-92 Cluster in Gastric Adenocarcinoma Cell Culture

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Jesper A. B. Strickertsson

2014-08-01

Full Text Available Chronic inflammation due to bacterial overgrowth of the stomach predisposes to the development of gastric cancer and is also associated with high levels of reactive oxygen species (ROS. In recent years increasing attention has been drawn to microRNAs (miRNAs due to their role in the pathogenesis of many human diseases including gastric cancer. Here we studied the impact of infection by the gram-positive bacteria Enterococcus faecalis (E. faecalis on global miRNA expression as well as the effect of ROS on selected miRNAs. Human gastric adenocarcinoma cell line MKN74 was infected with living E. faecalis for 24 h or for 5 days or with E. faecalis lysate for 5 days. The miRNA expression was examined by microarray analysis using Affymetrix GeneChip miRNA Arrays. To test the effect of ROS, MKN74 cells were treated with 100 mM tert-Butyl hydroperoxide (TBHP. Following 5 days of E. faecalis infection we found 91 differentially expressed miRNAs in response to living bacteria and 2 miRNAs responded to E. faecalis lysate. We verified the down-regulation of the miR-17-92 and miR-106-363 clusters and of other miRNAs involved in the oxidative stress-response by qRT-PCR. We conclude that only infection by living E. faecalis bacteria caused a significant global response in miRNA expression in the MKN74 cell culture. E. faecalis infection as well as ROS stimulation down-regulated the expression of the miR-17-92 cluster. We believe that these changes could reflect a general response of gastric epithelial cells to bacterial infections.

The development of a mini-array for estimating the disease state of gastric adenocarcinoma by array CGH

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Oga Atsunori

2008-12-01

Full Text Available Abstract Background The treatment strategy usually depends on the disease state in the individual patient. However, it is difficult to estimate the disease state before treatment in many patients. The purpose of this study was to develop a BAC (bacterial artificial chromosome mini-array allowing for the estimation of node metastasis, liver metastasis, peritoneal dissemination and the depth of tumor invasion in gastric cancers. Methods Initially, the DNA copy number aberrations (DCNAs were analyzed by array-based comparative genomic hybridization (aCGH in 83 gastric adenocarcinomas as a training-sample set. Next, two independent analytical methods were applied to the aCGH data to identify the BAC clones with DNA copy number aberrations that were linked with the disease states. One of the methods, a decision-tree model classifier, identified 6, 4, 4, 4, and 7 clones for estimating lymph node metastasis, liver metastasis, peritoneal dissemination, depth of tumor invasion, and histological type, respectively. In the other method, a clone-by-clone comparison of the frequency of the DNA copy number aberrations selected 26 clones to estimate the disease states. Results By spotting these 50 clones together with 26 frequently or rarely involved clones and 62 reference clones, a mini-array was made to estimate the above parameters, and the diagnostic performance of the mini-array was evaluated for an independent set of 30 gastric cancers (blinded – sample set. In comparison to the clinicopathological features, the overall accuracy was 66.7% for node metastasis, 86.7% for liver metastasis, 86.7% for peritoneal dissemination, and 96.7% for depth of tumor invasion. The intratumoral heterogeneity barely affected the diagnostic performance of the mini-array. Conclusion These results suggest that the mini-array makes it possible to determine an optimal treatment for each of the patients with gastric adenocarcinoma.

The development of a mini-array for estimating the disease state of gastric adenocarcinoma by array CGH

International Nuclear Information System (INIS)

Furuya, Tomoko; Uchiyama, Tetsuji; Adachi, Atsushi; Okada, Takae; Nakao, Motonao; Oga, Atsunori; Yang, Song-Ju; Kawauchi, Shigeto; Sasaki, Kohsuke

2008-01-01

The treatment strategy usually depends on the disease state in the individual patient. However, it is difficult to estimate the disease state before treatment in many patients. The purpose of this study was to develop a BAC (bacterial artificial chromosome) mini-array allowing for the estimation of node metastasis, liver metastasis, peritoneal dissemination and the depth of tumor invasion in gastric cancers. Initially, the DNA copy number aberrations (DCNAs) were analyzed by array-based comparative genomic hybridization (aCGH) in 83 gastric adenocarcinomas as a training-sample set. Next, two independent analytical methods were applied to the aCGH data to identify the BAC clones with DNA copy number aberrations that were linked with the disease states. One of the methods, a decision-tree model classifier, identified 6, 4, 4, 4, and 7 clones for estimating lymph node metastasis, liver metastasis, peritoneal dissemination, depth of tumor invasion, and histological type, respectively. In the other method, a clone-by-clone comparison of the frequency of the DNA copy number aberrations selected 26 clones to estimate the disease states. By spotting these 50 clones together with 26 frequently or rarely involved clones and 62 reference clones, a mini-array was made to estimate the above parameters, and the diagnostic performance of the mini-array was evaluated for an independent set of 30 gastric cancers (blinded – sample set). In comparison to the clinicopathological features, the overall accuracy was 66.7% for node metastasis, 86.7% for liver metastasis, 86.7% for peritoneal dissemination, and 96.7% for depth of tumor invasion. The intratumoral heterogeneity barely affected the diagnostic performance of the mini-array. These results suggest that the mini-array makes it possible to determine an optimal treatment for each of the patients with gastric adenocarcinoma

Genomic Alterations in Primary Gastric Adenocarcinomas Correlate with Clinicopathological Characteristics and Survival

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Marjan M. Weiss

2004-01-01

Full Text Available Background & aims: Pathogenesis of gastric cancer is driven by an accumulation of genetic changes that to a large extent occur at the chromosomal level. In order to investigate the patterns of chromosomal aberrations in gastric carcinomas, we performed genome‐wide microarray based comparative genomic hybridisation (microarray CGH. With this recently developed technique chromosomal aberrations can be studied with high resolution and sensitivity. Methods: Array CGH was applied to a series of 35 gastric adenocarcinomas using a genome‐wide scanning array with 2275 BAC and P1 clones spotted in triplicate. Each clone contains at least one STS for linkage to the sequence of the human genome. These arrays provide an average resolution of 1.4 Mb across the genome. DNA copy number changes were correlated with clinicopathological tumour characteristics as well as survival. Results: All thirty‐five cancers showed chromosomal aberrations and 16 of the 35 tumours showed one or more amplifications. The most frequent aberrations are gains of 8q24.2, 8q24.1, 20q13.12, 20q13.2, 7p11.2, 1q32.3, 8p23.1–p23.3, losses of 5q14.1, 18q22.1, 19p13.12–p13.3, 9p21.3–p24.3, 17p13.1–p13.3, 13q31.1, 16q22.1, 21q21.3, and amplifications of 7q21–q22, and 12q14.1–q21.1. These aberrations were correlated to clinicopathological characteristics and survival. Gain of 1q32.3 was significantly correlated with lymph node status (p=0.007. Tumours with loss of 18q22.1, as well as tumours with amplifications were associated with poor survival (p=0.02, both. Conclusions: Microarray CGH has revealed several chromosomal regions that have not been described before in gastric cancer at this frequency and resolution, such as amplification of at 7q21–q22 and 12q14.1–q21.1, as well gains at 1q32.3, 7p11.2, and losses at 13q13.1. Interestingly, gain of 1q32.3 and loss of 18q22.1 are associated with a bad prognosis indicating that these regions could harbour gene(s that may

Expression of a LINE-1 endonuclease variant in gastric cancer: its association with clinicopathological parameters

International Nuclear Information System (INIS)

Wang, Gangshi; Wu, Benyan; Wang, Mengwei; Gao, Jie; Huang, Haili; Tian, Yu; Xue, Liyan; Wang, Weihua; You, Weidi; Lian, Hongwei; Duan, Xiaojian

2013-01-01

Long interspersed nuclear element-1 (LINE-1 or L1), the most abundant and only autonomously active family of non-LTR retrotransposons in the human genome, expressed not only in the germ lines but also in somatic tissues. It contributes to genetic instability, aging, and age-related diseases, such as cancer. Our previous study identified in human gastric adenocarcinoma an upregulated transcript GCRG213, which shared 88% homology with human L1 sequence and contained a putative conserved apurinic/apyrimidinic endonucleas1 domain. Immunohistochemistry was carried out by using a monoclonal mouse anti-human GCRG213 protein (GCRG213p) antibody produced in our laboratory, on tissue microarray constructed with specimens from 175 gastric adenocarcinoma patients. The correlation between GCRG213p expression and patient clinicopathological parameters was evaluated. GCRG213p expression in gastric cancer cell lines were studied using Western blotting analysis. L1 promoter methylation status of gastric cancer cells was tested using methylation-specific PCR. BLASTP was used at the NCBI Blast server to identify GCRG213p sequence to any alignments in the Protein Data Bank databases. Most primary gastric cancer, lymph node metastases and gastric intestinal metaplasia glands showed positive GCRG213p immunoreactivity. High GCRG213p immunostaining score in the primary gastric cancer was positively correlated with tumor differentiation (well differentiated, p = 0.001), Lauren’s classification (intestinal type, p < 0.05) and a late age onset of gastric adenocarcinoma (≥65 yrs; p < 0.05). GCRG213p expression has no association with other clinicopathological parameters, including survival. Western blotting analysis of GCRG213p expression in gastric cancer cells indicated that GCRG213p level was higher in gastric cancer cell lines than in human normal gastric epithelium immortalized cell line GES-1. Partial methylation of L1 in gastric cancer cells was confirmed by methylation

Serum gastrin and cholecystokinin are associated with subsequent development of gastric cancer in a prospective cohort of Finnish smokers

DEFF Research Database (Denmark)

Murphy, Gwen; Abnet, Christian C; Choo-Wosoba, Hyoyoung

2017-01-01

Background: Gastrin, which induces gastric acid secretion, and a structurally similar hormone, cholecystokinin (CCK)-a potent acid inhibitor, may each play a role in gastric cancer. However, few studies have investigated this hypothesis in humans. We therefore investigated whether serum gastrin...... or CCK concentrations at baseline were associated with the incidence of gastric non-cardia adenocarcinomas (GNCA), oesophagogastric junctional adenocarcinomas (EGJA) or gastric carcinoid tumours over 24 years of follow-up in a study nested within the all-male Alpha-Tocopherol, Beta-Carotene Cancer...... suggest that high serum concentrations of gastrin may be associated independently with an increased risk of gastric cancer; the role of CCK in cancer risk is less clear....

DBGC: A Database of Human Gastric Cancer

Science.gov (United States)

Wang, Chao; Zhang, Jun; Cai, Mingdeng; Zhu, Zhenggang; Gu, Wenjie; Yu, Yingyan; Zhang, Xiaoyan

2015-01-01

The Database of Human Gastric Cancer (DBGC) is a comprehensive database that integrates various human gastric cancer-related data resources. Human gastric cancer-related transcriptomics projects, proteomics projects, mutations, biomarkers and drug-sensitive genes from different sources were collected and unified in this database. Moreover, epidemiological statistics of gastric cancer patients in China and clinicopathological information annotated with gastric cancer cases were also integrated into the DBGC. We believe that this database will greatly facilitate research regarding human gastric cancer in many fields. DBGC is freely available at http://bminfor.tongji.edu.cn/dbgc/index.do PMID:26566288

Epidermal growth factor receptor mutation in gastric cancer.

Science.gov (United States)

Liu, Zhimin; Liu, Lina; Li, Mei; Wang, Zhaohui; Feng, Lu; Zhang, Qiuping; Cheng, Shihua; Lu, Shen

2011-04-01

Epidermal growth factor receptor (EGFR) and Kirsten-RAS (KRAS) mutations have been identified as predictors of response to EGFR tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer. We aimed to screen the mutations of both genes in gastric carcinoma to detect the suitability of EGFR TKIs for patients with gastric carcinoma. We screened EGFR mutation in exons 19-21 and KRAS mutation in exon 2 in 58 gastric adenocarcinomas from China using high resolution melting analysis (HRMA). Positive samples were confirmed by DNA sequencing. Three EGFR missense mutations (5.2%) and 22 single nucleotide polymorphisms (SNP, Q787Q, 37.9%) were identified. To our knowledge, we report for the first time three mutation patterns of EGFR, Y801C, L858R and G863D, in gastric carcinoma. Two samples with EGFR mutation were mucinous adenocarcinoma. These three samples were collected from male patients aged over 75 years old. The frequency of KRAS mutation was 10.3% (6/58). The exclusiveness of EGFR and KRAS mutations was proven for the first time in gastric cancer. Gastric carcinoma of the mucinous adenocarcinoma type collected from older male patients may harbour EGFR mutations. The small subset of gastric adenocarcinoma patients may respond to EGFR TKIs.

[AFP-producing gastric cancer and hepatoid gastric cancer].

Science.gov (United States)

Wang, Y K; Zhang, X T

2017-11-23

AFP-producing gastric cancer(AFPGC) and hepatoid adenocarcinoma of the stomach (HAS) are two special subtypes of gastric cancer. There are both correlation and difference between them. AFPGC is usually identified as primary gastric cancer with serum AFP level more than 20 ng/ml or showed AFP positive staining by immunohistochemistry. The diagnosis of HAS is mainly dependent on the pathological character of hepatocellular carcinoma-like differentiation of gastric cancer. The morbidity of AFPGC and HAS are rather low, especially the incidence of HAS is about 1%. The prognoses of these two subtypes are poorer than that of common gastric adenocarcinoma, due to a high incidence rate of liver metastasis and lymph node metastasis. With the development of next-generation sequencing and other genomic technologies, gastric cancers, including these two rare subtypes, are now being investigated in more detail at the molecular level. Treatment remains the biggest challenge, early diagnosis and radical resection can dramatically improve patients'prognosis. Monitoring serum AFP and abdominal imaging examination during follow-up is important for early detection of liver metastasis. In combination with local treatment methods such as transarterial chemoembolization and radiofrequency ablation of liver may further extend patients'survival time. Targeted therapy owes a great potential value in the future.

Prevention of Gastric Cancer: Eradication of Helicobacter Pylori and Beyond

Directory of Open Access Journals (Sweden)

Tetsuya Tsukamoto

2017-08-01

Full Text Available Although its prevalence is declining, gastric cancer remains a significant public health issue. The bacterium Helicobacter pylori is known to colonize the human stomach and induce chronic atrophic gastritis, intestinal metaplasia, and gastric cancer. Results using a Mongolian gerbil model revealed that H. pylori infection increased the incidence of carcinogen-induced adenocarcinoma, whereas curative treatment of H. pylori significantly lowered cancer incidence. Furthermore, some epidemiological studies have shown that eradication of H. pylori reduces the development of metachronous cancer in humans. However, other reports have warned that human cases of atrophic metaplastic gastritis are already at risk for gastric cancer development, even after eradication of these bacteria. In this article, we discuss the effectiveness of H. pylori eradication and the morphological changes that occur in gastric dysplasia/cancer lesions. We further assess the control of gastric cancer using various chemopreventive agents.

[Value of immunocytochemistry in differential diagnosis of gastric adenocarcinoma, reactive mesothelial cells and malignant epithelial mesothelioma in metastatic effusion fluid].

Science.gov (United States)

Lyu, M; Cha, N; Zou, Y F; Leng, J H; Xu, L; Sun, Y; Hao, Y Y

2018-03-08

Objective: To investigate the diagnostic value of some antibodies in peritoneal fluid of patients with gastric cancer and malignant epithelioid mesothelioma in serous effusion. Methods: One hundred and eighty-two cases of serous effusion were collected at Jilin Cancer Hospital, from July 2012 to July 2016. The expression of GLUT1, CDX2, Villin, calretinin and WT1 was evaluated using SP immunocytochemical technique in peritoneal fluid samples collected from 98 patients with gastric cancer and 74 patients with reactive mesothelial cells. The expression of GLUT1, calretinin and WT1 was also evaluated in serous effusion from 10 patients with mesothelioma. Results: The sensitivity of GLUT1, CDX2 and Villin in adenocarcinoma cells was 91.8%(90/98), 68.4% (67/98) and 88.8%(87/98), respectively. The specificity was 95.9% (71/74), 100.0%(74/74) and 100.0% (74/74), respectively. The sensitivity of calretinin and WT1 for reactive mesothelium was 93.2% (69/74) and 79.7% (59/74), respectively. The specificity was 96.9% (95/98) and 100.0% (98/98), respectively. The sensitivity of GLUT1, calretinin and WT1 for mesothelioma was 9/10, 9/10 and 7/10. The reactivity of GLUT1, CDX2, Villin, calretinin and WT1 showed a significant difference ( P <0.01) between adenocarcinoma cells and reactive mesothelium. The reactivity of GLUT1 showed a significant difference ( P <0.01) between mesothelioma and reactive mesothelium. Conclusions: The optimal combination is a panel of GLUT1, CDX2, Villin, calretinin and WT1 for differential diagnosis between adenocarcinoma cells and reactive mesothelium in peritoneal fluid of patients with gastric cancer. Whereas GLUT1, calretinin and WT1 is the best for differential diagnosis between reactive mesothelium and mesothelioma in serous effusions.

Two distinct etiologies of gastric cardia adenocarcinoma: interactions among pH, Helicobacter pylori, and bile acids

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Ken-ichi eMukaisho

2015-05-01

Full Text Available Gastric cancer can be classified as cardia and noncardia subtypes according to the anatomic site. Although the gastric cancer incidence has decreased steadily in several countries over the past 50 years, the incidence of cardia cancers and esophageal adenocarcinoma (EAC continue to increase. The etiological factors involved in the development of both cardia cancers and EACs are associated with high animal fat intake, which causes severe obesity. Central obesity plays roles in cardiac-type mucosa lengthening and partial hiatus hernia development. There are two distinct etiologies of cardia cancer subtypes: one associated with gastroesophageal reflux (GER, which predominantly occurs in patients without Helicobacter pylori (H. pylori infection and resembles EAC, and the other associated with H. pylori atrophic gastritis, which resembles noncardia cancer. The former can be developed in the environment of high volume duodenal content reflux, including bile acids and a higher acid production in H. pylori–negative patients. N-nitroso compounds, which are generated from the refluxate that includes a large volume of bile acids and are stabilized in the stomach (which has high levels of gastric acid, play a pivotal role in this carcinogenesis. The latter can be associated with the changing colonization of H. pylori from the distal to the proximal stomach with atrophic gastritis because a high concentration of soluble bile acids in an environment of low acid production is likely to act as a bactericide or chemorepellent for H. pylori in the distal stomach with H. pylori infection. The manuscript introduces new insights in causative factors of adenocarcinoma of the cardia about the role of bile acids in gastro-esophageal refluxate based upon robust evidences supporting interactions among pH, H. pylori, and bile acids.

Stomach (Gastric) Cancer—Health Professional Version

Science.gov (United States)

Almost all gastric cancers are adenocarcinomas. Other types of gastric cancer are gastrointestinal carcinoid tumors, gastrointestinal stromal tumors, and lymphomas. Find evidence-based information on gastric cancer treatment, causes and prevention, screening, research, and statistics.

Concomitant chemo-radiation in therapeutic management of pancreatic and gastric adenocarcinoma

International Nuclear Information System (INIS)

Mornex, F.; Chauffert, B.

1998-01-01

The prognosis of pancreatic adenocarcinoma remains poor, with a 5-year survival rate lower than 5 %. Resection, the gold standard treatment, can be performed in less than 10 % of patients. Following surgery, the median survival is 12 months for the most favorable cancer patients. Concomitant chemo-radiation, as an adjuvant treatment is superior to surgery alone, in terms of survival; controlled trials are currently performed. Neo-adjuvant chemo-radiation is a new approach, potentially able to increase survival and resection rate. This work justifies the role of these schemes, in terms of modalities and potential advantages. A second part is dedicated to gastric carcinoma, with a review of the current results of chemo-radiation, whose efficiency, even though a trend can be observed, remains to be proven. Prospective adjuvant combined treatments are ongoing, in France and in the States. (authors)

Increased expression of argininosuccinate synthetase protein predicts poor prognosis in human gastric cancer

Science.gov (United States)

SHAN, YAN-SHEN; HSU, HUI-PING; LAI, MING-DERG; YEN, MENG-CHI; LUO, YI-PEY; CHEN, YI-LING

2015-01-01

Aberrant expression of argininosuccinate synthetase (ASS1, also known as ASS) has been found in cancer cells and is involved in the carcinogenesis of gastric cancer. The aim of the present study was to investigate the level of ASS expression in human gastric cancer and to determine the possible correlations between ASS expression and clinicopathological findings. Immunohistochemistry was performed on paraffin-embedded tissues to determine whether ASS was expressed in 11 of 11 specimens from patients with gastric cancer. The protein was localized primarily to the cytoplasm of cancer cells and normal epithelium. In the Oncomine cancer microarray database, expression of the ASS gene was significantly increased in gastric cancer tissues. To investigate the clinicopathological and prognostic roles of ASS expression, we performed western blot analysis of 35 matched specimens of gastric adenocarcinomas and normal tissue obtained from patients treated at the National Cheng Kung University Hospital. The ratio of relative ASS expression (expressed as the ASS/β-actin ratio) in tumor tissues to that in normal tissues was correlated with large tumor size (P=0.007) and with the tumor, node, metastasis (TNM) stage of the American Joint Committee on Cancer staging system (P=0.031). Patients whose cancer had increased the relative expression of ASS were positive for perineural invasion and had poor recurrence-free survival. In summary, ASS expression in gastric cancer was associated with a poor prognosis. Further study of mechanisms to silence the ASS gene or decrease the enzymatic activity of ASS protein has the potential to provide new treatments for patients with gastric cancer. PMID:25333458

Comparative genomic hybridization of cancer of the gastroesophageal junction: deletion of 14Q31-32.1 discriminates between esophageal (Barrett's) and gastric cardia adenocarcinomas

NARCIS (Netherlands)

H. van Dekken (Herman); E. Geelen; W.N.M. Dinjens (Winand); B.P.L. Wijnhoven (Bas); H.W. Tilanus (Hugo); H.J. Tanke (Hans); C. Rosenberg

1999-01-01

textabstractIncidence rates have risen rapidly for esophageal and gastric cardia adenocarcinomas. These cancers, arising at and around the gastroesophageal junction (GEJ), share a poor prognosis. In contrast, there is no consensus with respect to clinical staging

Helicobacter pylori-induced gastric pathology: insights from in vivo and ex vivo models

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Michael D. Burkitt

2017-02-01

Full Text Available Gastric colonization with Helicobacter pylori induces diverse human pathological conditions, including superficial gastritis, peptic ulcer disease, mucosa-associated lymphoid tissue (MALT lymphoma, and gastric adenocarcinoma and its precursors. The treatment of these conditions often relies on the eradication of H. pylori, an intervention that is increasingly difficult to achieve and that does not prevent disease progression in some contexts. There is, therefore, a pressing need to develop new experimental models of H. pylori-associated gastric pathology to support novel drug development in this field. Here, we review the current status of in vivo and ex vivo models of gastric H. pylori colonization, and of Helicobacter-induced gastric pathology, focusing on models of gastric pathology induced by H. pylori, Helicobacter felis and Helicobacter suis in rodents and large animals. We also discuss the more recent development of gastric organoid cultures from murine and human gastric tissue, as well as from human pluripotent stem cells, and the outcomes of H. pylori infection in these systems.

Hepatoid adenocarcinoma of the stomach: a case report

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Chung, Eun A; Yang, Ik; Lee, Yul; Chung, Soo Young; Kim, Ju Seup [College of Medicine, Hallym University, Seoul (Korea, Republic of)

1995-01-15

Hepatoid adenocarcinoma of the stomach is a gastric carcinoma with both adenocarcinomatous and hepatocellular carcinomatous differentiation. It usually produces large amount of serum alpha-fetoprotein. It often occurs in aged person, commonly located in the gastric antrum. Because of early lymph node and liver metastasis, prognosis is poor. A case of hepatoid adenocarcinoma of the stomach in a 49-year-old man is reported. The patient's serum alpha-fetoprotein level was high (3380 ng/ml). Liver function test was normal, otherwise. A mass was observed in right lobe of the liver on US and CT. It was hypervascular with increased uptake of lipiodol on hepatic arteriography. A large ulcerative tumor involving the gastric antrum and body was also found at barium study of the stomach. Subtotal gastrectomy nad right lobectomy of the liver resulted in rapid decrease in serum alpha-fetoprotein. Histopathologically the diagnosis was hepatoid adenocarcinoma of the stomach with liver metastasis.

Hepatoid adenocarcinoma of the stomach: a case report

International Nuclear Information System (INIS)

Chung, Eun A; Yang, Ik; Lee, Yul; Chung, Soo Young; Kim, Ju Seup

1995-01-01

Hepatoid adenocarcinoma of the stomach is a gastric carcinoma with both adenocarcinomatous and hepatocellular carcinomatous differentiation. It usually produces large amount of serum alpha-fetoprotein. It often occurs in aged person, commonly located in the gastric antrum. Because of early lymph node and liver metastasis, prognosis is poor. A case of hepatoid adenocarcinoma of the stomach in a 49-year-old man is reported. The patient's serum alpha-fetoprotein level was high (3380 ng/ml). Liver function test was normal, otherwise. A mass was observed in right lobe of the liver on US and CT. It was hypervascular with increased uptake of lipiodol on hepatic arteriography. A large ulcerative tumor involving the gastric antrum and body was also found at barium study of the stomach. Subtotal gastrectomy nad right lobectomy of the liver resulted in rapid decrease in serum alpha-fetoprotein. Histopathologically the diagnosis was hepatoid adenocarcinoma of the stomach with liver metastasis

A regulatory network for human adenocarcinoma

African Journals Online (AJOL)

AJL

2012-03-13

Mar 13, 2012 ... Human adenocarcinoma (AC) is the most frequently diagnosed human lung cancer and its absolute incidence is increasing ... Lung carcinomas are usually classified as small-cell lung ..... such as embryonic development, reproduction, and. TYMS .... homeostatic processes including stem cell maintenance,.

L-Dopa decarboxylase (DDC) constitutes an emerging biomarker in predicting patients' survival with stomach adenocarcinomas.

Science.gov (United States)

Florou, Dimitra; Papadopoulos, Iordanis N; Fragoulis, Emmanuel G; Scorilas, Andreas

2013-02-01

Stomach adenocarcinoma represents a major health problem and is regarded as the second commonest cause of cancer-associated mortality, universally, since it is still difficult to be perceived at a curable stage. Several lines of evidence have pointed out that the expression of L-Dopa decarboxylase (DDC) gene and/or protein becomes distinctively modulated in several human neuroendocrine neoplasms as well as adenocarcinomas. In order to elucidate the clinical role of DDC on primary gastric adenocarcinomas, we determined qualitatively and quantitatively the mRNA levels of the gene with regular PCR and real-time PCR by using the comparative threshold cycle method, correspondingly, and detected the expression of DDC protein by immunoblotting in cancerous and normal stomach tissue specimens. A statistically significant association was disclosed between DDC expression and gastric intestinal histotype as well as tumor localization at the distal third part of the stomach (p = 0.025 and p = 0.029, respectively). Univariate and multivariate analyses highlighted the powerful prognostic importance of DDC in relation to disease-free survival and overall survival of gastric cancer patients. According to Kaplan-Meier curves, the relative risk of relapse was found to be decreased in DDC-positive (p = 0.031) patients who, also, exhibited higher overall survival rates (p = 0.016) than those with DDC-negative tumors. This work is the first to shed light on the potential clinical usefulness of DDC, as an efficient tumor biomarker in gastric cancer. The provided evidence underlines the propitious predictive value of DDC expression in the survival of stomach adenocarcinoma patients.

Inactivation of Smad4 in gastric carcinomas.

Science.gov (United States)

Powell, S M; Harper, J C; Hamilton, S R; Robinson, C R; Cummings, O W

1997-10-01

Allelic loss of chromosome 18q has been noted in intestinal type gastric adenocarcinomas. Smad4 is a gene located at 18q that was recently cloned in humans and found to be significantly altered in pancreatic cancers. We sought to determine whether Smad4 genetic alterations played a significant role in gastric tumorigenesis by studying 35 gastric adenocarcinomas of all histopathological types and pathological stages. Microdissected specimens were used for mutational analysis of Smad4 at the nucleotide level, including the entire coding region and intron/exon boundaries. Allelic imbalance was also analyzed at the Smad4 locus using two nearby microsatellite markers. One case of apparent biallelic inactivation of Smad4 was found in our study of 35 gastric carcinomas. A nonsense point mutation at codon 334 was demonstrated, which, similar to other Smad4 mutations, is predicted to truncate the conserved COOH-terminal domain of this protein. This Smad4 C to T transition mutation was proven to be somatically acquired. Allelic loss was also noted on chromosome 18q at a marker near Smad4 in this mutated gastric cancer, apparently producing complete inactivation of Smad4 in this tumor. Significant 18q allelic loss (56% of 34 informative cases) was noted in our gastric carcinomas using microsatellite markers near the Smad4 locus, regardless of histological subtype or pathological stage. Additionally, three cases of microsatellite instability were observed. Thus, Smad4 inactivation was noted in our gastric carcinomas; however, this event was rare. The frequent loss of chromosomal arm 18q observed in gastric cancers suggests the presence of other tumor suppressor genes in this region that are involved in gastric tumorigenesis. Further studies are needed to identify these other targets of inactivation during gastric cancer development.

Different histological status of gastritis in superficial adenocarcinoma of the esophagogastric junction.

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Yamada, Masayoshi; Kushima, Ryoji; Oda, Ichiro; Mojtahed, Kaveh; Nonaka, Satoru; Suzuki, Haruhisa; Yoshinaga, Shigetaka; Matsubara, Akiko; Taniguchi, Hirokazu; Sekine, Shigeki; Saito, Yutaka; Shimoda, Tadakazu

2014-01-01

Although many gastric cancers arise in chronic gastritis, the association between adenocarcinoma of the esophagogastric junction and the status of background gastritis remains unclear. We aim to investigate the histological status of gastritis in the background fundic gland mucosa of adenocarcinoma of the esophagogastric junction. The present study included 121 consecutive patients with superficial adenocarcinoma of the esophagogastric junction obtained by surgical and/or endoscopic resection. We re-evaluated the histogenesis of adenocarcinoma of the esophagogastric junction, including the background fundic gland mucosa using the Updated Sydney System. The prevalence of histologic atrophic gastric mucosa with gastritis (positive gastritis), non-atrophic gastric mucosa without gastritis (negative gastritis) and Barrett's adenocarcinoma was examined. Histologic-positive gastritis was found in 67 (55%) of all patients, in 24 (38%) of 63 Barrett's adenocarcinoma patients and in 43 (74%) of 58 non-Barrett's adenocarcinoma patients (P gastritis patients `and younger age in non-Barrett's adenocarcinoma without gastritis patients were shown. There were no differences in clinicopathological features related to the gastritis status in Barrett's adenocarcinoma patients. Reflux esophagitis was observed in most (81%) of all patients, and 32 (74%) of the non-Barrett's adenocarcinoma with gastritis patients. In the 67 positive gastritis patients, the mean Updated Sydney System scores of glandular atrophy and intestinal metaplasia were 1.45 and 1.10, respectively, and these scores were higher in the non-Barrett's adenocarcinoma patients than in the Barrett's adenocarcinoma patients. This study suggests that about half of the patients with adenocarcinoma of the esophagogastric junction harbor histological gastritis. Adenocarcinoma of the esophagogastric junction is considered to be a heterogeneous entity, including Barrett's esophagus-related, positive gastritis-related, and

Comparative genomic hybridization of cancer of the gastroesophageal junction: deletion of 14Q31-32.1 discriminates between esophageal (Barrett's) and gastric cardia adenocarcinomas.

Science.gov (United States)

van Dekken, H; Geelen, E; Dinjens, W N; Wijnhoven, B P; Tilanus, H W; Tanke, H J; Rosenberg, C

1999-02-01

Incidence rates have risen rapidly for esophageal and gastric cardia adenocarcinomas. These cancers, arising at and around the gastroesophageal junction (GEJ), share a poor prognosis. In contrast, there is no consensus with respect to clinical staging resulting in possible adverse effects on treatment and survival. The goal of this study was to provide more insight into the genetic changes underlying esophageal and gastric cardia adenocarcinomas. We have used comparative genomic hybridization for a genetic analysis of 28 adenocarcinomas of the GEJ. Eleven tumors were localized in the distal esophagus and related to Barrett's esophagus, and 10 tumors were situated in the gastric cardia. The remaining seven tumors were located at the junction and could not be classified as either Barrett-related, or gastric cardia. We found alterations in all 28 neoplasms. Gains and losses were distinguished in comparable numbers. Frequent loss (> or = 25% of all tumors) was detected, in decreasing order of frequency, on 4pq (54%), 14q (46%), 18q (43%), 5q (36%), 16q (36%), 9p (29%), 17p (29%), and 21q (29%). Frequent gain (> or = 25% of all tumors) was observed, in decreasing order of frequency, on 20pq (86%), 8q (79%), 7p (61%), 13q (46%), 12q (39%), 15q (39%), 1q (36%), 3q (32%), 5p (32%), 6p (32%), 19q (32%), Xpq (32%), 17q (29%), and 18p (25%). Nearly all patients were male, and loss of chromosome Y was frequently noted (64%). Recurrent high-level amplifications (> 10% of all tumors) were seen at 8q23-24.1, 15q25, 17q12-21, and 19q13.1. Minimal overlapping regions could be determined at multiple locations (candidate genes are in parentheses): minimal regions of overlap for deletions were assigned to 3p14 (FHIT, RCA1), 5q14-21 (APC, MCC), 9p21 (MTS1/CDKN2), 14q31-32.1 (TSHR), 16q23, 18q21 (DCC, P15) and 21q21. Minimal overlapping amplified sites could be seen at 5p14 (MLVI2), 6p12-21.1 (NRASL3), 7p12 (EGFR), 8q23-24.1 (MYC), 12q21.1, 15q25 (IGF1R), 17q12-21 (ERBB2/HER2-neu), 19q

Randomized Multicenter Phase II Study of Modified Docetaxel, Cisplatin, and Fluorouracil (DCF) Versus DCF Plus Growth Factor Support in Patients With Metastatic Gastric Adenocarcinoma: A Study of the US Gastric Cancer Consortium.

Science.gov (United States)

Shah, Manish A; Janjigian, Yelena Y; Stoller, Ronald; Shibata, Stephen; Kemeny, Margaret; Krishnamurthi, Smitha; Su, Yungpo Bernard; Ocean, Allyson; Capanu, Marinela; Mehrotra, Bhoomi; Ritch, Paul; Henderson, Charles; Kelsen, David P

2015-11-20

Docetaxel, cisplatin, and fluorouracil (DCF) is a standard first-line three-drug chemotherapy regimen for advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma and is associated with significant toxicity. We examined the safety and efficacy of a modified DCF (mDCF) regimen in a randomized multicenter phase II study. Previously untreated patients with metastatic gastric or GEJ adenocarcinoma were randomly assigned to receive either mDCF (fluorouracil 2,000 mg/m2 intravenously [IV] over 48 hours, docetaxel 40 mg/m2 IV on day 1, cisplatin 40 mg/m2 IV on day 3, every 2 weeks) or parent DCF (docetaxel 75 mg/m2, cisplatin 75 mg/m2, and fluorouracil 750 mg/m2 IV over 5 days with granulocyte colony-stimulating factor, every 3 weeks). The study had 90% power to differentiate between 6-month progression-free survival of 26% and 43%, with type I and II error rates of 10% each. An early stopping rule for toxicity was included, defined as grade 3 to 4 adverse event rate > 70% in the first 3 months. From November 2006 to June 2010, 85 evaluable patients were enrolled (male, n = 61; female, n = 24; median age, 58 years; Karnofsky performance status, 90%; GEJ, n = 28; gastric, 57). mDCF (n = 54) toxicity rates included 54% grade 3 to 4 toxicity (22% hospitalized) within the first 3 months and 76% grade 3 to 4 toxicity over the course of treatment. The DCF arm (n = 31) closed early because of toxicity, with rates of 71% grade 3 to 4 toxicity (52% hospitalized) within 3 months and 90% grade 3 to 4 toxicity over the course of treatment. Six-month PFS was 63% (95% CI, 48% to 75%) for mDCF and 53% (95% CI, 34% to 69%) for DCF. Median overall survival was improved for mDCF (18.8 v 12.6 months; P = .007). mDCF is less toxic than parent DCF, even when supported with growth factors, and is associated with improved efficacy. mDCF should be considered a standard first-line option for patients with metastatic gastric or GEJ adenocarcinoma.

Alcohol consumption, cigarette smoking and risk of subtypes of oesophageal and gastric cancer: A prospective cohort study

NARCIS (Netherlands)

Steevens, J.; Schouten, L.J.; Goldbohm, R.A.; Brandt, P.A. van den

2010-01-01

Objective: Alcohol consumption and cigarette smoking may be differentially associated with oesophageal squamous cell carcinoma (OSCC), oesophageal adenocarcinoma (OAC), gastric cardia adenocarcinoma (GCA) and gastric non-cardia adenocarcinoma (GNCA). However, because this was based on retrospective

Use of serum and peritoneal CEA and CA19-9 in prediction of peritoneal dissemination and survival of gastric adenocarcinoma patients: are they prognostic factors?

Science.gov (United States)

Hasbahceci, M; Malya, F U; Kunduz, E; Guler, M; Unver, N; Akcakaya, A

2018-04-01

Introduction To evaluate the impact of serum and peritoneal levels of tumour markers on peritoneal carcinomatosis and survival in gastric adenocarcinoma. Materials and methods Patients with gastric adenocarcinoma were evaluated with regard to serum and peritoneal carcinoembryonic antigen (CEA) and CA19-9. Numeric values and groupings based on serum and peritoneal cutoff values were used. Development of peritoneal carcinomatosis, including positive washing cytology, was regarded as main outcome. Gastric cancer outcomes as disease free and overall survival were analysed. Results There were 67 patients with a mean age of 60 ± 11 years. Positive peritoneal washing cytology was significantly associated with serum CA19-9 and high serum CA 19-9 group (P = 0.033 and P = 0.011, respectively). High peritoneal CEA was shown to be significantly associated with peritoneal carcinomatosis (P = 0.032). After a median follow up of 17 months, 48 patients (71.7%) were alive. Patients with peritoneal carcinomatosis showed significant poorer prognosis as shown by overall survival rate of 28.6%. Only serum CEA was significantly associated with lower disease free and overall survival (P = 0.002 and P = 0.001, respectively). Discussion and conclusion Serum CEA is shown to be significantly associated with poor prognosis for gastric cancer patients. Serum level of CA19-9 and high peritoneal CEA levels are significant predictors for positive peritoneal washing cytology and the development of peritoneal carcinomatosis, respectively. Therefore, the possible impact of serum and peritoneal tumor markers especially on the staging and prognosis of gastric cancer remains to be clarified by future studies.

X irradiation combined with TNF alpha-related apoptosis-inducing ligand (TRAIL) reduces hypoxic regions of human gastric adenocarcinoma xenografts in SCID mice

International Nuclear Information System (INIS)

Takahashi, Momoko; Yasui, Hironobu; Ogura, Aki; Asanuma, Taketoshi; Inanami, Osamu; Kubota, Nobuo; Tsujitani, Michihiko; Kuwabara, Mikinori

2008-01-01

Our previous study showed that X irradiation induced the expression of death receptor DR5 on the cell surface in tumor cell lines under not only normoxia but also hypoxia. X irradiation combined with TNF α-related apoptosis-inducing ligand (TRAIL), which is the ligand of DR5, induced apoptosis in vitro (Takahashi et al., (2007) Journal of Radiation Research, 48: 461-468). In this report, we examined the in vivo antitumor efficacy of X irradiation combined with TRAIL treatment in tumor xenograft models derived from human gastric adenocarcinoma MKN45 and MKN28 cells in severe combined immunodeficiency (SCID) mice. X irradiation combined with TRAIL synergistically suppressed the tumor growth rates in the xenograft models derived from MKN45 and MKN28 cells, which have wild type Tp53 and mutated Tp53, respectively, indicating that the antitumor effects occurred in a Tp53-independent manner. Histological analysis showed that the combination of X irradiation and TRAIL induced caspase-3-dependent apoptotic cell death. Moreover, the immunohistochemical detection of hypoxic regions using the hypoxic marker pimonidazole revealed that caspase-3-dependent apoptosis occurred in the hypoxic regions in the tumors. These results indicated that X irradiation combined with TRAIL may be a useful treatment to reduce tumor growth in not only normoxic but also hypoxic regions. (author)

Metastatic Carcinoma Occurring in a Gastric Hyperplastic Polyp Mimicking Primary Gastric Cancer: The First Reported Case

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Gabriel M. Groisman

2014-01-01

Full Text Available Hyperplastic polyps of the stomach are regarded as benign. However, in rare cases they may contain incipient primary carcinomas. To our knowledge, breast carcinoma metastatic to a gastric hyperplastic polyp has not yet been reported. We describe the case of a 69-year-old woman to whom a gastric polyp was endoscopically excised. The patient had previously undergone a right mastectomy for mixed, invasive ductal and lobular carcinoma 5 years earlier. Histological sections from the gastric lesion showed typical features of hyperplastic polyp with foci of poorly differentiated adenocarcinoma including signet ring cells infiltrating the lamina propria. The histologic findings were consistent with a primary gastric cancer. However, the carcinoma cells were immunopositive for estrogen and progesterone receptors and GATA3 and negative for CDX2, Hep Par 1, and MUC5AC. E-cadherin showed membranous reactivity in some of the carcinoma cells while in others it was negative. Accordingly, metastatic mixed, lobular and ductal breast carcinoma was diagnosed. We conclude that metastatic adenocarcinoma mimicking primary gastric cancer can be rarely encountered in hyperplastic gastric polyps.

A changing gastric environment leads to adaptation of lipopolysaccharide variants in Helicobacter pylori populations during colonization.

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Anna Skoglund

2009-06-01

Full Text Available The human gastric pathogen Helicobacter pylori colonizes the stomachs of half of the human population, and causes development of peptic ulcer disease and gastric adenocarcinoma. H. pylori-associated chronic atrophic gastritis (ChAG with loss of the acid-producing parietal cells, is correlated with an increased risk for development of gastric adenocarcinoma. The majority of H. pylori isolates produce lipopolysaccharides (LPS decorated with human-related Lewis epitopes, which have been shown to phase-vary in response to different environmental conditions. We have characterized the adaptations of H. pylori LPS and Lewis antigen expression to varying gastric conditions; in H. pylori isolates from mice with low or high gastric pH, respectively; in 482 clinical isolates from healthy individuals and from individuals with ChAG obtained at two time points with a four-year interval between endoscopies; and finally in isolates grown at different pH in vitro. Here we show that the gastric environment can contribute to a switch in Lewis phenotype in the two experimental mouse models. The clinical isolates from different human individuals showed that intra-individual isolates varied in Lewis antigen expression although the LPS diversity was relatively stable within each individual over time. Moreover, the isolates demonstrated considerable diversity in the levels of glycosylation and in the sizes of fucosylated O-antigen chains both within and between individuals. Thus our data suggest that different LPS variants exist in the colonizing H. pylori population, which can adapt to changes in the gastric environment and provide a means to regulate the inflammatory response of the host during disease progression.

Conventional cytogenetic characterization of a new cell line, ACP01, established from a primary human gastric tumor

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E.M. Lima

2004-12-01

Full Text Available Gastric cancer is the second most frequent type of neoplasia and also the second most important cause of death in the world. Virtually all the established cell lines of gastric neoplasia were developed in Asian countries, and western countries have contributed very little to this area. In the present study we describe the establishment of the cell line ACP01 and characterize it cytogenetically by means of in vitro immortalization. Cells were transformed from an intestinal-type gastric adenocarcinoma (T4N2M0 originating from a 48-year-old male patient. This is the first gastric adenocarcinoma cell line established in Brazil. The most powerful application of the cell line ACP01 is in the assessment of cytotoxicity. Solid tumor cell lines from different origins have been treated with several conventional and investigational anticancer drugs. The ACP01 cell line is triploid, grows as a single, non-organized layer, similar to fibroblasts, with focus formation, heterogeneous division, and a cell cycle of approximately 40 h. Chromosome 8 trisomy, present in 60% of the cells, was the most frequent cytogenetic alteration. These data lead us to propose a multifactorial triggering of gastric cancer which evolves over multiple stages involving progressive genetic changes and clonal expansion.

A report of three cases with thrombotic thrombocytopenic purpura (TTP) secondary to an occult gastric adenocarcinoma

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Forat, Y.M.; Hashemian, Z.; Nazmieh, H.; Ghadimi, H.R.

2009-01-01

Thrombotic thrombocytopenic purpura (TTP) is a disseminated form of thrombotic microangiopathy with clinical findings consisting of fever, microangiopathic hemolytic anemia (MAHA), thrombocytopenia, fluctuating neurologic impairment and renal dysfunction. However, Microangiopathic hemolytic anemia has been described in association with disseminated malignancies, most commonly adenocarcinoma of the breast or stomach. We present three patients with microangiopathic anemia in whom metastatic cancer was finally diagnosed; however, they died of refractory hemolytic anemia in the end. The occurrence of microangiopathic hemolytic anemia and thrombocytopenia in patients with disseminated malignant in gastric adenocarsinoma is well documented. Therefore, the diagnosis of tumor-associated TTP should be considered in unresponsive TTP patient treated with plasmapheresis. (author)

Compared With Elastin Stains, h-Caldesmon and Desmin Offer Superior Detection of Vessel Invasion in Gastric, Pancreatic, and Colorectal Adenocarcinomas.

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Ekinci, Özgür; Öğüt, Betül; Çelik, Bülent; Dursun, Ayşe

2018-06-01

The presence of vessel invasion is considered indicative of a poor prognosis in many malignant tumors. We aimed to compare the sensitivity of elastin stains (van Gieson's and orcein methods) with 2 smooth muscle markers (h-caldesmon and desmin) in gastric, pancreatic, and colorectal adenocarcinoma specimens. We used 27 (29.3%) gastric, 35 (38.0%) pancreatic, and 30 (32.6%) colorectal resection specimens. We applied a provisional classification of vessel invasion patterns: type A, a focus with a nearby artery unaccompanied by a vein; type T, a focus at the invasive front without an unaccompanied artery; and type X, foci that only appeared by any of the 4 stains used. There were 369 foci. The smooth muscle markers were more sensitive than the elastin stains, and h-caldesmon more sensitive than desmin, in all types. Among the 139 type A foci, 33 (23.7%) were positive by desmin and h-caldesmon, whereas the elastin stains were not ( P = .001). h-Caldesmon was the only positive marker in 11 (7.9%; P = .011). Among the 78 type T foci, 21 (26.9%) were positive by desmin and h-caldesmon, when both elastin stains were negative ( P = .000). In 16 (20.5%) foci, h-caldesmon was the only positive marker ( P = .002). Among 152 type X foci, 91 (59.9%) were positive by all markers, 26 (17.1%) by both desmin and h-caldesmon, and 9 (5.9%) by only the 2 elastin stains ( P = .001). We recommend these stains for suspect foci in gastric, pancreatic, and colorectal adenocarcinoma specimens. They might highlight both predictable and unpredictable foci.

Impact of marital status on survival of gastric adenocarcinoma patients: Results from the Surveillance Epidemiology and End Results (SEER) Database

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Qiu, Miaozhen; Yang, Dajun; Xu, Ruihua

2016-01-01

Marital status was found to be an independent prognostic factor for survival in various cancer types. In this study, we used the Surveillance, Epidemiology and End Results database to analyze the survival difference among different marital status in the United States. Gastric adenocarcinoma patients from 2004?2012 were enrolled for study. The 5-year cause specific survival (CSS) was our primary endpoint. Totally 29,074 eligible patients were identified. We found that more male patients were m...

[18F] FDG PET in gastric non-Hodgkin's lymphoma

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Rodriguez, M.; Ahlstroem, H.; Sundin, A.; Rehn, S.; Hagberg, H.; Glimelius, B.; Sundstroem, C.

1997-01-01

The possibility of using [ 18 F] FDG PET for assessment of tumor extension in primary gastric non-Hodgkin's lymphoma (NHL) was studied in 8 patients (6 high-grade and 2 low-grade, one of the MALT type) and in a control group of 7 patients (5 patients with NHL without clinical signs of gastric involvement, 1 patient with NHL and benign gastric ulcer and 1 patient with adenocarcinoma of the stomach). All patients with gastric NHL and the two with benign gastric ulcer and adenocarcinoma, respectively, underwent endoscopy including multiple biopsies for histopathological diagnosis. All patients with high-grade and one of the two with low-grade NHL and the patient with adenocarcinoma displayed high gastric uptake of [ 18 F] FDG corresponding to the pathological findings at endoscopy and/or CT. No pathological tracer uptake was seen in the patient with low-grade gastric NHL of the MALT type. In 6/8 patients with gastric NHL, [ 18 F] FDG PET demonstrated larger tumor extension in the stomach than was found at endoscopy, and there was high tracer uptake in the stomach in two patients who were evaluated as normal on CT. [ 18 F] FDG PET correctly excluded gastric NHL in the patient with a benign gastric ulcer and in the patients with NHL without clinical signs of gastric involvement. Although the experience is as yet limited, [ 18 F] FDG PET affords a novel possibility for evaluation of gastric NHL and would seem valuable as a complement to endoscopy and CT in selected patients, where the technique can yield additional information decisive for the choice of therapy. (orig.)

Nut and peanut butter consumption and the risk of esophageal and gastric cancer subtypes.

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Hashemian, Maryam; Murphy, Gwen; Etemadi, Arash; Dawsey, Sanford M; Liao, Linda M; Abnet, Christian C

2017-09-01

Background: Nut consumption has been associated with decreased risk of colorectal, endometrial, lung, and pancreatic cancers. Polyphenols, fiber, vitamins, and minerals in nuts may confer this observed protective effect. To our knowledge, no prospective study has evaluated the effect of nut consumption on esophageal and gastric cancers. Objective: The objective was to evaluate the associations between nut and peanut butter consumption and the risk of esophageal and gastric cancers and their different subtypes. Design: In this study we used data from the NIH-AARP Diet and Health Study, which enrolled 566,407 persons who were 50-71 y old at baseline (1995-1996). The median follow-up time was 15.5 y. Intakes of nuts and peanut butter were assessed through the use of a validated food-frequency questionnaire. We used Cox proportional hazard models to estimate HRs and 95% CIs for esophageal and gastric cancers and their subtypes. Results: We identified 966 incident cases of esophageal adenocarcinomas, 323 cases of esophageal squamous cell carcinoma, 698 cases of gastric cardia adenocarcinoma, and 732 cases of gastric noncardia adenocarcinoma. Compared with those who did not consume nuts or peanut butter [lowest category of consumption (C0)], participants in the highest category of nut consumption (C3) had a lower risk of developing gastric noncardia adenocarcinoma [C3 compared with C0, HR: 0.73 (95% CI: 0.57, 0.94)]. This inverse association was also seen for peanut butter consumption [C3 compared with C0, HR: 0.75 (95% CI: 0.60, 0.94)]. We observed no significant associations between the highest and lowest intakes of nuts or peanut butter and the risk of gastric cardia adenocarcinoma, esophageal adenocarcinoma, or esophageal squamous cell carcinoma. Conclusions: Among older American adults, both nut and peanut butter consumption were inversely associated with the risk of gastric noncardia adenocarcinoma. This trial was registered at clinicaltrials.gov as NCT00340015. �

Staging of gastric adenocarcinoma using two-phase spiral CT: correlation with pathologic staging

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Seo, Tae Seok; Lee, Dong Ho; Ko, Young Tae; Lim, Joo Won

1998-01-01

To correlate the preoperative staging of gastric adenocarcinoma using two-phase spiral CT with pathologic staging. One hundred and eighty patients with gastric cancers confirmed during surgery underwent two-phase spiral CT, and were evaluated retrospectively. CT scans were obtained in the prone position after ingestion of water. Scans were performed 35 and 80 seconds after the start of infusion of 120mL of non-ionic contrast material with the speed of 3mL/sec. Five mm collimation, 7mm/sec table feed and 5mm reconstruction interval were used. T-and N-stage were determined using spiral CT images, without knowledge of the pathologic results. Pathologic staging was later compared with CT staging. Pathologic T-stage was T1 in 70 cases(38.9%), T2 in 33(18.3%), T3 in 73(40.6%), and T4 in 4(2.2%). Type-I or IIa elevated lesions accouted for 10 of 70 T1 cases(14.3%) and flat or depressed lesions(type IIb, IIc, or III) for 60(85.7%). Pathologic N-stage was NO in 85 cases(47.2%), N1 in 42(23.3%), N2 in 31(17.2%), and N3 in 22(12,2%). The detection rate of early gastric cancer using two-phase spiral CT was 100.0%(10 of 10 cases) among elevated lesions and 78.3%(47 of 60 cases) among flat or depressed lesions. With regard to T-stage, there was good correlation between CT image and pathology in 86 of 180 cases(47.8%). Overstaging occurred in 23.3%(42 of 180 cases) and understaging in 28.9%(52 of 180 cases). With regard to N-stage, good correlation between CT image and pathology was noted in 94 of 180 cases(52.2%). The rate of understaging(31.7%, 57 of 180 cases) was higher than that of overstaging(16.1%, 29 of 180 cases)(p<0.001). The detection rate of early gastric cancer using two-phase spiral CT was 81.4%, and there was no significant difference in detectability between elevated and depressed lesions. Two-phase spiral CT for determing the T-and N-stage of gastric cancer was not effective;it was accurate in abont 50% of cases understaging tended to occur.=20

Primary gastric chorioadenocarcinoma: a needle in a haystack

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Teresa G. Hayes

2011-04-01

Full Text Available Primary gastric chorioadenocarcinoma (PGC is an exceedingly rare neoplasm which is often misdiagnosed as gastric adenocarcinoma at presentation. A markedly elevated serum beta human chorionic gonadotrophin (Beta HCG level is a characteristic feature of this tumor. A 44 year old white male presented with generalized abdominal pain and fullness, tarry black stools and weight loss of 3 months duration. Medical work-up including imaging with CT scans revealed the presence of a gastric mass and multiple liver metastases. Tumor markers were significant for a Beta HCG of 23717.5 MIU/ML. Scrotal ultrasound did not show the presence of a testicular mass. Upper GI endoscopy with biopsy was positive for a poorly differentiated adenocarcinoma with Beta HCG staining on immunohistochemistry. The patient was diagnosed with metastatic PGC. He received four cycles of chemotherapy with Bleomycin, Etoposide and Cisplatinum. At the end of the fourth cycle, Beta HCG was 23 MIU/ML. CT scan for restaging, however showed an increase in the size of the metastatic lesions. The patient subsequently became profoundly pancytopenic, developed disseminated intravascular coagulation (DIC and expired 12 months after initial presentation. PGC genetically and morphologically represents an adenocarcinoma and a choriocarcinoma. The significance of an elevated serum Beta HCG is controversial and it may have a role in evaluating response to treatment and tumor recurrence. Curative resection, appropriate chemotherapy and the absence of metastatic lesions is associated with improved survival. Hence, a high index of suspicion must be maintained to diagnose this tumor correctly at presentation and tailor therapy accordingly.

Rituximab Treatment Prevents Lymphoma Onset in Gastric Cancer Patient-Derived Xenografts

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Simona Corso

2018-05-01

Full Text Available Patient-Derived Xenografts (PDXs, entailing implantation of cancer specimens in immunocompromised mice, are emerging as a valuable translational model that could help validate biologically relevant targets and assist the clinical development of novel therapeutic strategies for gastric cancer.More than 30% of PDXs generated from gastric carcinoma samples developed human B-cell lymphomas instead of gastric cancer. These lymphomas were monoclonal, Epstein Barr Virus (EBV positive, originated tumorigenic cell cultures and displayed a mutational burden and an expression profile distinct from gastric adenocarcinomas. The ability of grafted samples to develop lymphomas did not correlate with patient outcome, nor with the histotype, the lymphocyte infiltration level, or the EBV status of the original gastric tumor, impeding from foreseeing lymphoma onset. Interestingly, lymphoma development was significantly more frequent when primary rather than metastatic samples were grafted.Notably, the development of such lympho-proliferative disease could be prevented by a short rituximab treatment upon mice implant, without negatively affecting gastric carcinoma engraftment.Due to the high frequency of human lymphoma onset, our data show that a careful histologic analysis is mandatory when generating gastric cancer PDXs. Such care would avoid misleading results that could occur if testing of putative gastric cancer therapies is performed in lymphoma PDXs. We propose rituximab treatment of mice to prevent lymphoma development in PDX models, averting the loss of human-derived samples.

Epstein-Barr virus infection and gastric carcinoma in São Paulo State, Brazil

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L.F. Lopes

2004-11-01

Full Text Available Epstein-Barr virus (EBV is a ubiquitous herpesvirus, and most people have serological evidence of previous viral infection at adult age. EBV is associated with infectious mononucleosis and human cancers, including some lymphomas and gastric carcinomas. Although EBV was first reported in lymphoepithelioma-like gastric carcinoma, the virus was also found in conventional adenocarcinomas. In the present study, 53 gastric carcinomas diagnosed in São Paulo State, Brazil, were evaluated for EBV infection by non-isotopic in situ hybridization with a biotinylated probe (Biotin-AGACACCGTCCTCACCACCC GGGACTTGTA directed to the viral transcript EBER-I, which is actively expressed in EBV latently infected cells. EBV infection was found in 6 of 53 (11.32% gastric carcinomas, mostly from male patients (66.7%, with a mean age of 59 years old. Most EBV-positive tumors were in gastric antrum. Two EBV-positive tumors (33.3% were conventional adenocarcinomas, whereas four (66.7% were classified as lymphoepithelioma-like carcinomas. EBV infection in gastric carcinomas was reported elsewhere in frequencies that range from 5.6% (Korea up to 18% (Germany. In Brazil, a previous work found EBV infection in 4 of 80 (5% gastric carcinomas, whereas another study found 4.7 and 11.2% of EBV-positive gastric carcinomas of Brazilians of Japanese origin or not, respectively. In the present study, the frequency of EBV-positive gastric carcinomas is similar to that reported in other series, and the clinicopathologic characteristics of these EBV-positive tumors are in agreement with the data in the literature.

Follistatin is a novel biomarker for lung adenocarcinoma in humans.

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Fangfang Chen

Full Text Available Follistatin (FST, a single chain glycoprotein, is originally isolated from follicular fluid of ovary. Previous studies have revealed that serum FST served as a biomarker for pregnancy and ovarian mucinous tumor. However, whether FST can serve as a biomarker for diagnosis in lung adenocarcinoma of humans remains unclear.The study population consisted of 80 patients with lung adenocarcinoma, 40 patients with ovarian adenocarcinoma and 80 healthy subjects. Serum FST levels in patients and healthy subjects were measured using ELISA. The results showed that the positive ratio of serum FST levels was 51.3% (41/80, which was comparable to the sensitivity of FST in 40 patients with ovarian adenocarcinoma (60%, 24/40 using the 95th confidence interval for the healthy subject group as the cut-off value. FST expressions in lung adenocarcinoma were examined by immunohistochemical staining, we found that lung adenocarcinoma could produce FST and there was positive correlation between the level of FST expression and the differential degree of lung adenocarcinoma. Furthermore, the results showed that primary cultured lung adenocarcinoma cells could secrete FST, while cells derived from non-tumor lung tissues almost did not produce FST. In addition, the results of CCK8 assay and flow cytometry showed that using anti-FST monoclonal antibody to neutralize endogenous FST significantly augmented activin A-induced lung adenocarcinoma cells apoptosis.These data indicate that lung adenocarcinoma cells can secret FST into serum, which may be beneficial to the survival of adenocarcinoma cells by neutralizing activin A action. Thus, FST can serve as a promising biomarker for diagnosis of lung adenocarcinoma and a useful biotherapy target for lung adenocarcinoma.

Scopadulciol, Isolated from Scoparia dulcis, Induces β-Catenin Degradation and Overcomes Tumor Necrosis Factor-Related Apoptosis Ligand Resistance in AGS Human Gastric Adenocarcinoma Cells.

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Fuentes, Rolly G; Toume, Kazufumi; Arai, Midori A; Sadhu, Samir K; Ahmed, Firoj; Ishibashi, Masami

2015-04-24

Scopadulciol (1), a scopadulan-type diterpenoid, was isolated from Scoparia dulcis along with three other compounds (2-4) by an activity-guided approach using the TCF reporter (TOP) luciferase-based assay system. A fluorometric microculture cytotoxicity assay (FMCA) revealed that compound 1 was cytotoxic to AGS human gastric adenocarcinoma cells. The treatment of AGS cells with 1 decreased β-catenin levels and also inhibited its nuclear localization. The pretreatment of AGS cells with a proteasome inhibitor, either MG132 or epoxomicin, protected against the degradation of β-catenin induced by 1. The 1-induced degradation of β-catenin was also abrogated in the presence of pifithrin-α, an inhibitor of p53 transcriptional activity. Compound 1 inhibited TOP activity in AGS cells and downregulated the protein levels of cyclin D1, c-myc, and survivin. Compound 1 also sensitized AGS cells to tumor necrosis factor-related apoptosis ligand (TRAIL)-induced apoptosis by increasing the levels of the death receptors, DR4 and DR5, and decreasing the level of the antiapoptotic protein Bcl-2. Collectively, our results demonstrated that 1 induced the p53- and proteasome-dependent degradation of β-catenin, which resulted in the inhibition of TCF/β-catenin transcription in AGS cells. Furthermore, 1 enhanced apoptosis in TRAIL-resistant AGS when combined with TRAIL.

A new score for screening of malnutrition in patients with inoperable gastric adenocarcinoma.

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Esfahani, Ali; Somi, Mohammad Hossein; Asghari Jafarabadi, Mohammad; Ostadrahimi, Alireza; Ghayour Nahand, Mousa; Fathifar, Zahra; Doostzadeh, Akram; Ghoreishi, Zohreh

2017-06-01

Malnutrition is common in patients with gastric cancer. Early identification of malnourished patients results in improving quality of life. We aimed to assess the nutritional status of patients with inoperable gastric adenocarcinoma (IGA) and finding a precise malnutrition screening score for these patients before the onset of chemotherapy. Nutritional status was assessed using patient generated subjective global assessment (PG-SGA), visceral proteins, and high-sensitivity C reactive protein. Tumor markers of carcinoembryonic antigen (CEA), carbohydrate antigen 125 (CA-125) and CA 19-9 and their association with nutritional status were assessed. Then a new score for malnutrition screening was defined. Seventy-one patients with IGA completed the study. Malnourished and well-nourished patients (based on PG-SGA) were statistically different regarding albumin, prealbumin and CA-125. The best cut-off value for prealbumin for prediction of malnutrition was determined at 0.20 mg/dl and using known cut-off values for albumin (3.5 g/dl) and CA-125 (35 U/ml), a new score was defined for malnutrition screening named MS-score. According to MS-score, 92% of the patients had malnutrition and it could predict malnutrition with 96.8% sensitivity, 50% specificity and accuracy of 91.4%. MS-score has been suggested as an available and easy-to-use tool for malnutrition screening in patients with IGA. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Current Status on Stem Cells and Cancers of the Gastric Epithelium

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Werner Hoffmann

2015-08-01

Full Text Available Gastric cancer is still a leading cause of cancer-related mortality worldwide in spite of declining incidence. Gastric cancers are, essentially, adenocarcinomas and one of the strongest risk factors is still infection with Helicobacter pylori. Within the last years, it became clear that gastric self-renewal and carcinogenesis are intimately linked, particularly during chronic inflammatory conditions. Generally, gastric cancer is now regarded as a disease resulting from dysregulated differentiation of stem and progenitor cells, mainly due to an inflammatory environment. However, the situation in the stomach is rather complex, consisting of two types of gastric units which show bidirectional self-renewal from an unexpectedly large variety of progenitor/stem cell populations. As in many other tumors, cancer stem cells have also been characterized for gastric cancer. This review focuses on the various gastric epithelial stem cells, how they contribute to self-renewal and which routes are known to gastric adenocarcinomas, including their stem cells.

Gastric mucosa in Mongolian and Japanese patients with gastric cancer and Helicobacter pylori infection

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Matsuhisa, Takeshi; Yamaoka, Yoshio; Uchida, Tomohisa; Duger, Davaadorj; Adiyasuren, Battulga; Khasag, Oyuntsetseg; Tegshee, Tserentogtokh; Tsogt-Ochir, Byambajav

2015-01-01

AIM: To investigate the characteristics of gastric cancer and gastric mucosa in a Mongolian population by comparison with a Japanese population. METHODS: A total of 484 Mongolian patients with gastric cancer were enrolled to study gastric cancer characteristics in Mongolians. In addition, a total of 208 Mongolian and 3205 Japanese consecutive outpatients who underwent endoscopy, had abdominal complaints, no history of gastric operation or Helicobacter pylori eradication treatment, and no use of gastric secretion inhibitors such as histamine H2-receptor antagonists or proton pump inhibitors were enrolled. This study was conducted with the approval of the ethics committees of all hospitals. The triple-site biopsy method was used for the histologic diagnosis of gastritis and H. pylori infection in all Mongolian and Japanese cases. The infection rate of H. pylori and the status of gastric mucosa in H. pylori-infected patients were compared between Mongolian and Japanese subjects. Age (± 5 years), sex, and endoscopic diagnosis were matched between the two countries. RESULTS: Approximately 70% of Mongolian patients with gastric cancer were 50-79 years of age, and approximately half of the cancers were located in the upper part of the stomach. Histologically, 65.7% of early cancers exhibited differentiated adenocarcinoma, whereas 73.9% of advanced cancers displayed undifferentiated adenocarcinoma. The infection rate of H. pylori was higher in Mongolian than Japanese patients (75.9% vs 48.3%, P gastritis changed from antrum-predominant gastritis to corpus-predominant gastritis with age in both populations. CONCLUSION: Gastric cancer was located in the upper part of the stomach in half of the Mongolian patients; Mongolian patients were infected with non-East-Asian-type H. pylori. PMID:26217093

Braf, Kras and Helicobacter pylori epigenetic changes-associated chronic gastritis in Egyptian patients with and without gastric cancer.

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Sabry, Dina; Ahmed, Rasha; Abdalla, Sayed; Fathy, Wael; Eldemery, Ahmed; Elamir, Azza

2016-06-01

We aimed to study MLH1 and MGMT methylation status in Helicobacter pylori-associated chronic gastritis in Egyptian patients with and without gastric cancer. 39 patients were included in our study. They were divided into 2 groups; patients without (group I) and with gastric adenocarcinoma (group II). Patients were subjected to clinical examination, abdominal ultrasound and upper endoscopy for gastric biopsy. Biopsies were subjected to urease test, histological examination, and DNA purification. H. pylori, Braf, Kras, MLH1 and MGMT methylation were assessed by quantitative PCR. DNA sequencing was performed to assess Braf and Kras genes mutation. qPCR of H. pylori was significantly higher in patients with adenocarcinoma (group II) than those without adenocarcinoma (group I); with a p gastritis patients. DNA sequence analysis of Braf (codon 12) and Kras (codon 600) had genes mutation in gastric adenocarcinoma versus chronic gastritis. H. pylori may cause epigenetic changes predisposing the patients to cancer stomach. Estimation of H. pylori by qPCR can be a good predictor to adenocarcinoma. Braf and Kras genes mutation were reveled in gastritis and adenocarcinoma patients.

Gastric cancer metastasis mimicking primary lung cancer - case report and review of the literature

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Escuissato, Dante Luiz; Ledesma, Jorge Alberto; Urban, Linei Augusta Brolini Delle; Liu, Cristhian Bau; Reis Filho, Jorge Sergio; Oliveira Filho, Adilson Gil; Ferri, Mauricio Beller; Hossaka, Marco Aurelio

2002-01-01

Gastric cancer frequently presents intraperitoneal spread. Distant metastasis are rare. The authors describe a case of a 47-year-old white man, long-term cigarette smoker, who had a right upper lobe mass seen on plain films and computed tomography of the chest. A gastric adenocarcinoma was concomitantly diagnosed by endoscopic examination. A bronchoscopy guided biopsy showed that the lung mass was in fact a metastasis from gastric adenocarcinoma. In this article, the imaging findings of gastric cancer and the patterns of dissemination to other organs are reviewed. (author)

[{sup 18}F] FDG PET in gastric non-Hodgkin`s lymphoma

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Rodriguez, M. [Dept. of Diagnostic Radiology, Uppsala Univ., Akademiska Sjukhuset (Sweden); Ahlstroem, H. [Dept. of Diagnostic Radiology, Uppsala Univ., Akademiska Sjukhuset (Sweden)]|[PET Centre, Uppsala Univ., Akademiska Sjukhuset (Denmark); Sundin, A. [PET Centre, Uppsala Univ., Akademiska Sjukhuset (Denmark); Rehn, S.; Hagberg, H.; Glimelius, B. [Dept. of Oncology, Uppsala Univ., Akademiska Sjukhuset (Sweden); Sundstroem, C. [Dept. of Pathology, Uppsala Univ., Akademiska Sjukhuset (Sweden)

1997-12-31

The possibility of using [{sup 18}F] FDG PET for assessment of tumor extension in primary gastric non-Hodgkin`s lymphoma (NHL) was studied in 8 patients (6 high-grade and 2 low-grade, one of the MALT type) and in a control group of 7 patients (5 patients with NHL without clinical signs of gastric involvement, 1 patient with NHL and benign gastric ulcer and 1 patient with adenocarcinoma of the stomach). All patients with gastric NHL and the two with benign gastric ulcer and adenocarcinoma, respectively, underwent endoscopy including multiple biopsies for histopathological diagnosis. All patients with high-grade and one of the two with low-grade NHL and the patient with adenocarcinoma displayed high gastric uptake of [{sup 18}F] FDG corresponding to the pathological findings at endoscopy and/or CT. No pathological tracer uptake was seen in the patient with low-grade gastric NHL of the MALT type. In 6/8 patients with gastric NHL, [{sup 18}F] FDG PET demonstrated larger tumor extension in the stomach than was found at endoscopy, and there was high tracer uptake in the stomach in two patients who were evaluated as normal on CT. [{sup 18}F] FDG PET correctly excluded gastric NHL in the patient with a benign gastric ulcer and in the patients with NHL without clinical signs of gastric involvement. Although the experience is as yet limited, [{sup 18}F] FDG PET affords a novel possibility for evaluation of gastric NHL and would seem valuable as a complement to endoscopy and CT in selected patients, where the technique can yield additional information decisive for the choice of therapy. (orig.).

SUVmax of 18F-FDG PET/CT correlates to expression of major chemotherapy-related tumor markers and serum tumor markers in gastric adenocarcinoma patients.

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Bai, Lu; Guo, Chi-Hua; Zhao, Yan; Gao, Jun-Gang; Li, Miao; Shen, Cong; Guo, You-Min; Duan, Xiao-Yi

2017-06-01

The expression of P53 was previously found by us significantly correlated with maximal standardized uptake value (SUVmax) in non-small cell lung cancer (NSCLC) patients. Hence, the aim of this study was to clarify the relationship between SUVmax and the status of the chemotherapy-related tumor marker expression or serum tumor markers in gastric adenocarcinoma patients. Sixty-four gastric adenocarcinoma patients who underwent 18F-FDG PET/CT prior to treatment were enrolled in this study. Immunohistochemistry was performed to detect changes of Her-2, P53 and Survivin in lesions, and electrochemiluminescence (ECL) method was used to quantify expression of serum CA72-4, CA19-9 and CEA of these patients. Then, the relationships between these parameters above were assessed by Spearman correlation analysis. Also, receiver-operating characteristic (ROC) curve was performed to determine the best cut-off value of SUVmax for suggesting chemotherapy resistant tumor markers. Besides, we identified a linear correlation to estimate the equations between SUVmax and the serum tumor markers. Our results showed that higher SUVmax was detected in patients with positive expression of Her-2 and P53, compared with negative groups. The Spearman correlation analysis showed that SUVmax was associated with Her-2 or P53 with the moderate relevant Pearson correlation coefficient. ROC curve analysis showed that the sensitivity and specificity of SUVmax for suggesting Her-2 or P53-positive, when the cut-off value of SUVmax was set at 3.25 or 5.45, respectively. Moreover, the relationship between SUVmax and serum tumor markers were analyzed by linear correlation analysis, and serum CA72-4 and CA19-9 could be used as independent parameters to establish an equation for SUVmax by the linear regression models. These results suggested that SUVmax of 18F-FDG PET/CT could be used to predict and evaluate Her-2 or P53 related chemotherapy resistance of gastric adenocarcinoma patients. However, before PET

Sentinel node mapping for gastric cancer: a prospective multicenter trial in Japan.

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Kitagawa, Yuko; Takeuchi, Hiroya; Takagi, Yu; Natsugoe, Shoji; Terashima, Masanori; Murakami, Nozomu; Fujimura, Takashi; Tsujimoto, Hironori; Hayashi, Hideki; Yoshimizu, Nobunari; Takagane, Akinori; Mohri, Yasuhiko; Nabeshima, Kazuhito; Uenosono, Yoshikazu; Kinami, Shinichi; Sakamoto, Junichi; Morita, Satoshi; Aikou, Takashi; Miwa, Koichi; Kitajima, Masaki

2013-10-10

Complicated gastric lymphatic drainage potentially undermines the utility of sentinel node (SN) biopsy in patients with gastric cancer. Encouraged by several favorable single-institution reports, we conducted a multicenter, single-arm, phase II study of SN mapping that used a standardized dual tracer endoscopic injection technique. Patients with previously untreated cT1 or cT2 gastric adenocarcinomas 4 cm. We observed no serious adverse effects related to endoscopic tracer injection or the SN mapping procedure. The endoscopic dual tracer method for SN biopsy was confirmed as safe and effective when applied to the superficial, relatively small gastric adenocarcinomas included in this study.

Seventh edition (2010) of the AJCC/UICC staging system for gastric adenocarcinoma: is there room for improvement?

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Patel, Manali I; Rhoads, Kim F; Ma, Yifei; Ford, James M; Visser, Brendan C; Kunz, Pamela L; Fisher, George A; Chang, Daniel T; Koong, Albert; Norton, Jeffrey A; Poultsides, George A

2013-05-01

The gastric cancer AJCC/UICC staging system recently underwent significant revisions, but studies on Asian patients have reported a lack of adequate discrimination between various consecutive stages. We sought to validate the new system on a U.S. population database. California Cancer Registry data linked to the Office of Statewide Health Planning and Development discharge abstracts were used to identify patients with gastric adenocarcinoma (esophagogastric junction and gastric cardia tumors excluded) who underwent curative-intent surgical resection in California from 2002 to 2006. AJCC/UICC stage was recalculated based on the latest seventh edition. Overall survival probabilities were calculated using the Kaplan-Meier method. Of 1905 patients analyzed, 54 % were males with a median age of 70 years. Median number of pathologically examined lymph nodes was 12 (range, 1-90); 40 % of patients received adjuvant chemotherapy, and 31 % received adjuvant radiotherapy. The seventh edition AJCC/UICC system did not distinguish outcome adequately between stages IB and IIA (P = 0.40), or IIB and IIIA (P = 0.34). By merging stage II into 1 category and moving T2N1 to stage IB and T2N2, T1N3 to stage IIIA, we propose a new grouping system with improved discriminatory ability In this first study validating the new seventh edition AJCC/UICC staging system for gastric cancer on a U.S. population with a relatively limited number of lymph nodes examined, we found stages IB and IIA, as well as IIB and IIIA to perform similarly. We propose a revised stage grouping for the AJCC/UICC staging system that better discriminates between outcomes.

A method for establishing human primary gastric epithelial cell culture from fresh surgical gastric tissues.

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Aziz, Faisal; Yang, Xuesong; Wen, Qingping; Yan, Qiu

2015-08-01

At present, biopsy specimens, cancer cell lines and tissues obtained by gastric surgery are used in the study and analysis of gastric cancer, including the molecular mechanisms and proteomics. However, fibroblasts and other tissue components may interfere with these techniques. Therefore, the present study aimed to develop a procedure for the isolation of viable human gastric epithelial cells from gastric surgical tissues. A method was developed to culture human gastric epithelial cells using fresh, surgically excised tissues and was evaluated using immunocytochemistry, periodic acid-Schiff (PAS) staining and cell viability assays. Low cell growth was observed surrounding the gastric tissue on the seventh day of tissue explant culture. Cell growth subsequently increased, and at 12 days post-explant a high number of pure epithelial cells were detected. The gastric cancer cells exhibited rapid growth with a doubling time of 13-52 h, as compared to normal cells, which had a doubling time of 20-53 h. Immunocytochemical analyses of primary gastric cells revealed positive staining for cytokeratin 18 and 19, which indicated that the culture was comprised of pure epithelial cells and contained no fibroblasts. Furthermore, PAS staining demonstrated that the cultured gastric cells produced neutral mucin. Granulin and carbohydrate antigen 724 staining confirmed the purity of gastric cancer and normal cells in culture. This method of cell culture indicated that the gastric cells in primary culture consisted of mucin-secreting gastric epithelial cells, which may be useful for the study of gastric infection with Helicobacter pylori and gastric cancer.

Characterization of fasted human gastric fluid for relevant rheological parameters and gastric lipase activities

DEFF Research Database (Denmark)

Pedersen, Pernille Barbre; Vilmann, Peter; Bar-Shalom, Daniel

2013-01-01

be considered important during development of gastric simulated media. Further, the activity of the HGL is active even under fasted gastric conditions and might contribute to the digestion and emulsification of lipid-based drug delivery systems in the entire gastrointestinal tract. HGL should therefore......PURPOSE: To characterize human gastric fluid with regard to rheological properties and gastric lipase activity. In addition, traditional physicochemical properties were determined. METHODS: Fasted HGA were collected from 19 healthy volunteers during a gastroscopic examination. Rheological...... be considered in gastric evaluation of lipid-based drug delivery systems....

Gastric adenocarcinoma in a patient with X-linked agammaglobulinemia and HIV: Case report and review of the literature

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Joud Hajjar

2016-09-01

Full Text Available X-linked agammaglobulinemia (XLA is an X-linked inherited disease usually caused by a germline mutation in the BTK gene leading to Bruton’s tyrosine kinase deficiency, which results in the impaired development of B-lymphocytes and a subsequent lack of immunoglobulin production. Patients with XLA have an increased susceptibility to bacterial and viral infections, and multiple case reports have been published regarding an association between XLA and gastrointestinal (GI malignancy. Here, we describe a case of a 25-year-old man with XLA and HIV, who developed gastric adenocarcinoma. Previously reported cases of XLA and GI malignancy are also reviewed and summarized.

An exceptional collision tumor: gastric calcified stromal tumor and ...

African Journals Online (AJOL)

The authors report an exceptional case of collision tumor comprised of a gastric calcified stromal tumor and a pancreatic adenocarcinoma. The pancreatic tumor was detected fortuitously on the histological exam of resection specimen. Key words: Collision tumor, stromal tumor, adenocarcinoma ...

Inhibition of neutrophil elastase and metalloprotease-9 of human adenocarcinoma gastric cells by chamomile (Matricaria recutita L.) infusion.

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Bulgari, Michela; Sangiovanni, Enrico; Colombo, Elisa; Maschi, Omar; Caruso, Donatella; Bosisio, Enrica; Dell'Agli, Mario

2012-12-01

This study investigated whether the antiinflammatory effect of chamomile infusion at gastric level could be ascribed to the inhibition of metalloproteinase-9 and elastase. The infusions from capitula and sifted flowers (250-1500 µg/mL) and individual flavonoids (10 µM) were tested on phorbol 12-myristate 13-acetate-stimulated AGS cells and human neutrophil elastase. The results indicate that the antiinflammatory activity associated with chamomile infusions from both the capitula and sifted flowers is most likely due to the inhibition of neutrophil elastase and gastric metalloproteinase-9 activity and secretion; the inhibition occurring in a concentration dependent manner. The promoter activity was inhibited as well and the decrease of metalloproteinase-9 expression was found to be associated with the inhibition of NF-kB driven transcription. The results further indicate that the flavonoid-7-glycosides, major constituents of chamomile flowers, may be responsible for the antiinflammatory action of the chamomile infusion observed here. Copyright © 2012 John Wiley & Sons, Ltd.

Autoimmune gastritis mediated by CD4+ T cells promotes the development of gastric cancer.

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Nguyen, Thanh-Long M; Khurana, Shradha S; Bellone, Clifford J; Capoccia, Benjamin J; Sagartz, John E; Kesman, Russell A; Mills, Jason C; DiPaolo, Richard J

2013-04-01

Chronic inflammation is a major risk factor for cancer, including gastric cancers and other gastrointestinal cancers. For example, chronic inflammation caused by autoimmune gastritis (AIG) is associated with an increased risk of gastric polyps, gastric carcinoid tumors, and possibly adenocarcinomas. In this study, we characterized the progression of gastric cancer in a novel mouse model of AIG. In this model, disease was caused by CD4(+) T cells expressing a transgenic T-cell receptor specific for a peptide from the H(+)/K(+) ATPase proton pump, a protein expressed by parietal cells in the stomach. AIG caused epithelial cell aberrations that mimicked most of those seen in progression of human gastric cancers, including chronic gastritis followed by oxyntic atrophy, mucous neck cell hyperplasia, spasmolytic polypeptide-expressing metaplasia, dysplasia, and ultimately gastric intraepithelial neoplasias. Our work provides the first direct evidence that AIG supports the development of gastric neoplasia and provides a useful model to study how inflammation drives gastric cancer. ©2013 AACR.

Tumor response evaluation after neoadjuvant chemotherapy in locally advanced gastric adenocarcinoma: a prospective, multi-center cohort study

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De Martini, Paolo; Ceresoli, Marco; Mari, Giulio M.; Costanzi, Andrea; Maggioni, Dario; Pugliese, Raffaele; Ferrari, Giovanni

2017-01-01

Background To verify the prognostic value of the pathologic and radiological tumor response after neoadjuvant chemotherapy in the treatment of locally advanced gastric adenocarcinoma. Methods A total of 67 patients with locally advanced gastric cancer (clinical ≥ T2 or nodal disease and without evidence of distant metastases) underwent perioperative chemotherapy (ECF or ECX regimen) from December 2009 through June 2015 in two surgical units. Histopathological and radiological response to chemotherapy were evaluated by using tumor regression grade (TRG) (Becker’s criteria) and volume change assessed by CT. Results Fifty-one (86%) patients completed all chemotherapy scheduled cycles successfully and surgery was curative (R0) in 64 (97%) subjects. The histopathological analysis showed 19 (29%) specimens with TRG1 (less than 10% of vital tumor left) and 25 (37%) patients had partial or complete response (CR) assessed by CT scan. Median disease free survival (DFS) and overall survival (OS) were 25.70 months (range, 14.52–36.80 months) and 36.60 months (range, 24.3–52.9 months), respectively. The median follow up was 27 months (range, 5.00–68.00 months). Radiological response and TRG were found to be a prognostic factor for OS and DFS, while tumor histology was not significantly related to survival. Conclusions Both radiological response and TRG have been shown as promising survival markers in patients treated with perioperative chemotherapy for locally advanced gastric cancer. Other predictive markers of response to chemotherapy are strongly required. PMID:29299362

Characterization and significance of ACE2 and Mas receptor in human colon adenocarcinoma.

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Bernardi, Stella; Zennaro, Cristina; Palmisano, Silvia; Velkoska, Elena; Sabato, Nicoletta; Toffoli, Barbara; Giacomel, Greta; Buri, Luigi; Zanconati, Fabrizio; Bellini, Giuseppe; Burrell, Louise M; De Manzini, Nicolò; Fabris, Bruno

2012-03-01

A new arm of the renin-angiotensin system (RAS) has been recently characterized; this includes angiotensin converting enzyme (ACE)2 and angiotensin (Ang)1-7, a heptapeptide acting through the Mas receptor (MasR). Recent studies show that Ang1-7 has an antiproliferative action on lung adenocarcinoma cells. The aim of this study was to characterize RAS expression in human colon adenocarcinoma and to investigate whether Ang1-7 exerts an antiproliferative effect on human colon adenocarcinoma cells. Gene, protein expression and enzymatic activity of the main components of the RAS were determined on non-neoplastic colon mucosa as well as on the tumor mass and the mucosa taken 5 cm distant from it, both collected from patients with colon adenocarcinoma. Two different human colon cancer cell lines were treated with AngII and Ang1-7. The novel finding of this study was that MasR was significantly upregulated in colon adenocarcinoma compared with non-neoplastic colon mucosa, which showed little or no expression of it. ACE gene expression and enzymatic activity were also increased in the tumors. However, AngII and Ang1-7 did not have any pro-/antiproliferative effects in the cell lines studied. The data suggest that upregulation of the MasR could be used as a diagnostic marker of colon adenocarcinoma.

Translating Developmental Principles to Generate Human Gastric Organoids

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Alexandra K. Eicher

2018-01-01

Full Text Available Gastric diseases, including peptic ulcer disease and gastric cancer, are highly prevalent in human beings. Despite this, the cellular biology of the stomach remains poorly understood relative to other gastrointestinal organs such as the liver, intestine, and colon. In particular, little is known about the molecular basis of stomach development and the differentiation of gastric lineages. Although animal models are useful for studying gastric development, function, and disease, there are major structural and physiological differences in human stomachs that render these models insufficient. To look at gastric development, function, and disease in a human context, a model system of the human stomach is imperative. This review details how this was achieved through the directed differentiation of human pluripotent stem cells in a 3-dimensional environment into human gastric organoids (HGOs. Similar to previous work that has generated human intestine, colon, and lung tissue in vitro, HGOs were generated in vitro through a step-wise differentiation designed to mimic the temporal-spatial signaling dynamics that control stomach development in vivo. HGOs can be used for a variety of purposes, including genetic modeling, drug screening, and potentially even in future patient transplantation. Moreover, HGOs are well suited to study the development and interactions of nonepithelial cell types, such as endothelial, neuronal, and mesenchymal, which remain almost completely unstudied. This review discusses the basics of stomach morphology, function, and developmental pathways involved in generating HGOs. We also highlight important gaps in our understanding of how epithelial and mesenchymal interactions are essential for the development and overall function of the human stomach.

Crosstalk between EGFR and integrin affects invasion and proliferation of gastric cancer cell line, SGC7901

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Dan L

2012-10-01

Full Text Available Li Dan,1,* Ding Jian,2,* Lin Na,1 Wang Xiaozhong,1 1Digestive Department, the Union Hospital of Fujian Medical University, Fujian, People’s Republic of China; 2Digestive Department, the First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, People’s Republic of China*These authors contributed equally to this workBackground/objective: To investigate the crosstalk between epidermal growth factor receptor (EGFR and integrin-mediated signal transduction pathways in human gastric adenocarcinoma cells.Methods: EGF was used as a ligand of EGFR to stimulate the gastric adenocarcinoma cell, SGC7901. Signal molecules downstream of the integrin, FAK(Y397 and p130cas(Y410 phosphorylation, were measured by immunoprecipitation and western blot. Fibronectin (Fn was used as a ligand of integrin to stimulate the same cell line. Signal molecules downstream of EGFR and extracellular signal-regulated kinase (ERK general phosphorylation were also measured. Focal adhesion kinase (FAK small-interfering RNA was designed and transfected into SGC7901 cells to decrease the expression of FAK. Modified Boyden chambers and MTT assay were used to examine the effect of FAK inhibition on the invasiveness and proliferation of SGC7901.Results: EGF activated FAK(Y397 and p130cas(Y410 phosphorylation, while Fn activated ERK general phosphorylation. Inhibition of FAK expression decreased p130cas(Y410 phosphorylation activated by EGF and ERK general phosphorylation activated by Fn, also decreased the invasiveness and proliferation of SGC7901 cells activated by EGF or Fn.Conclusion: There is crosstalk between EGFR and integrin signal transduction. FAK may be a key cross point of the two signal pathways and acts as a potential target for human gastric cancer therapy.Keywords: gastric adenocarcinoma, epidermal growth factor receptor, integrin, focal adhesion kinase, crosstalk

IRGM gene polymorphisms and risk of gastric cancer.

NARCIS (Netherlands)

Burada, F.; Plantinga, T.S.; Ioana, M.; Rosentul, D.; Angelescu, C.; Joosten, L.A.B.; Netea, M.G.; Saftoiu, A.

2012-01-01

OBJECTIVE: The study aimed to assess the possible association of polymorphisms in the autophagy gene IRGM (rs13361189 and rs4958847) with the risk of gastric cancer. METHODS: A total of 102 patients with gastric adenocarcinoma, 52 with chronic gastritis and 351 healthy controls were included in this

Poncirin Induces Apoptosis in AGS Human Gastric Cancer Cells through Extrinsic Apoptotic Pathway by up-Regulation of Fas Ligand.

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Saralamma, Venu Venkatarame Gowda; Nagappan, Arulkumar; Hong, Gyeong Eun; Lee, Ho Jeong; Yumnam, Silvia; Raha, Suchismita; Heo, Jeong Doo; Lee, Sang Joon; Lee, Won Sup; Kim, Eun Hee; Kim, Gon Sup

2015-09-18

Poncirin, a natural bitter flavanone glycoside abundantly present in many species of citrus fruits, has various biological benefits such as anti-oxidant, anti-microbial, anti-inflammatory and anti-cancer activities. The anti-cancer mechanism of Poncirin remains elusive to date. In this study, we investigated the anti-cancer effects of Poncirin in AGS human gastric cancer cells (gastric adenocarcinoma). The results revealed that Poncirin could inhibit the proliferation of AGS cells in a dose-dependent manner. It was observed Poncirin induced accumulation of sub-G1 DNA content, apoptotic cell population, apoptotic bodies, chromatin condensation, and DNA fragmentation in a dose-dependent manner in AGS cells. The expression of Fas Ligand (FasL) protein was up-regulated dose dependently in Poncirin-treated AGS cells Moreover, Poncirin in AGS cells induced activation of Caspase-8 and -3, and subsequent cleavage of poly(ADP-ribose) polymerase (PARP). Inhibitor studies' results confirm that the induction of caspase-dependent apoptotic cell death in Poncirin-treated AGS cells was led by the Fas death receptor. Interestingly, Poncirin did not show any effect on mitochondrial membrane potential (ΔΨm), pro-apoptotic proteins (Bax and Bak) and anti-apoptotic protein (Bcl-xL) in AGS-treated cells followed by no activation in the mitochondrial apoptotic protein caspase-9. This result suggests that the mitochondrial-mediated pathway is not involved in Poncirin-induced cell death in gastric cancer. These findings suggest that Poncirin has a potential anti-cancer effect via extrinsic pathway-mediated apoptosis, possibly making it a strong therapeutic agent for human gastric cancer.

Krukenberg tumor after gastric bypass for morbid obesity: Bariatric surgery and gastric cancer

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Pablo Menéndez

2013-06-01

Full Text Available Gastric by-pass is one of the most performed surgical procedure in bariatric surgery. Neoplasm within gastric remnant is a slightly frequent complication (only six cases have been described but with important survival consequences. We present a case of a patient who developed an adenocarcinoma in excluded stomach, after three years of bariatric surgery; the tumor was incidentally discovered after a gynecological surgery for uterine myomas. Different diagnostic modalities for the excluded stomach were analyzed.

A protein and mRNA expression-based classification of gastric cancer.

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Setia, Namrata; Agoston, Agoston T; Han, Hye S; Mullen, John T; Duda, Dan G; Clark, Jeffrey W; Deshpande, Vikram; Mino-Kenudson, Mari; Srivastava, Amitabh; Lennerz, Jochen K; Hong, Theodore S; Kwak, Eunice L; Lauwers, Gregory Y

2016-07-01

The overall survival of gastric carcinoma patients remains poor despite improved control over known risk factors and surveillance. This highlights the need for new classifications, driven towards identification of potential therapeutic targets. Using sophisticated molecular technologies and analysis, three groups recently provided genetic and epigenetic molecular classifications of gastric cancer (The Cancer Genome Atlas, 'Singapore-Duke' study, and Asian Cancer Research Group). Suggested by these classifications, here, we examined the expression of 14 biomarkers in a cohort of 146 gastric adenocarcinomas and performed unsupervised hierarchical clustering analysis using less expensive and widely available immunohistochemistry and in situ hybridization. Ultimately, we identified five groups of gastric cancers based on Epstein-Barr virus (EBV) positivity, microsatellite instability, aberrant E-cadherin, and p53 expression; the remaining cases constituted a group characterized by normal p53 expression. In addition, the five categories correspond to the reported molecular subgroups by virtue of clinicopathologic features. Furthermore, evaluation between these clusters and survival using the Cox proportional hazards model showed a trend for superior survival in the EBV and microsatellite-instable related adenocarcinomas. In conclusion, we offer as a proposal a simplified algorithm that is able to reproduce the recently proposed molecular subgroups of gastric adenocarcinoma, using immunohistochemical and in situ hybridization techniques.

Induction of apoptosis in human breast adenocarcinoma MCF-7 ...

African Journals Online (AJOL)

Induction of apoptosis in human breast adenocarcinoma MCF-7 cells by tannic acid and resveratrol. Ahu Soyocak, Didem Turgut Cosan, Ayse Basaran, Hasan Veysi Gunes, Irfan Degirmenci, Fezan Sahin Mutlu ...

Lauren classification and individualized chemotherapy in gastric cancer

OpenAIRE

MA, JUNLI; SHEN, HONG; KAPESA, LINDA; ZENG, SHAN

2016-01-01

Gastric cancer is one of the most common malignancies worldwide. During the last 50 years, the histological classification of gastric carcinoma has been largely based on Lauren's criteria, in which gastric cancer is classified into two major histological subtypes, namely intestinal type and diffuse type adenocarcinoma. This classification was introduced in 1965, and remains currently widely accepted and employed, since it constitutes a simple and robust classification approach. The two histol...

Estudo citofotométrico da expressão dos marcadores tumorais Caspase-3 e Ki-67 no adenocarcinoma gástrico Cytophotometric study of the expression of tumoral markers Caspase-3 and Ki-67 in gastric adenocarcinoma

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Pedro Manuel Gonzales Cuellar

2007-06-01

marcadores Ki-67 e Caspase-3 com a leitura de 14 lâminas, observamos que existe diferença significativa (PBACKGROUND: Gastric tumorigenesis is a complex mechanism where genetic, enviromental and infeccious interferences may occur. In the last few years, advances in molecular biology brought a new way in the research of the malignancies using tumoral markers and imunohistochemistry. AIM: To describe the cytophotometric expression of tumoral markers Ki-67 and caspase-3, analyzing optical density and labeling index as parameters in gastric adenocarcinoma. To compare the labeling index and optical density of Ki-67 and Caspase-3 in gastric adenocarcinoma. METHODS: Fifty eight paraffin blocks containing gastric adenocarcinomas specimens were collected in the Serviços de Anátomo-Patologia do Hospital do Gama - Brasília (DF and Hospital Dom Orione - Araguaina (TO, being analyzed at CITOLAB - Cytology and Hystopathology Laboratory Ltda, in Curitiba (PR. A total of 31 of the blocks were used for hystological studies. Immunohistochemistry was performed utilizing the SAMBA 4000 computerized analysis system. RESULTS: Of the 31 slides studies, 15 (48% were marked by Ki-67, 22 (71% were marked by Caspase-3 and 14 (45% were marked by both of the tumoral markers. CONCLUSIONS: Cytophotometric expression of Ki-67 was observed in 15 of the slides studied, presenting an average labeling index of 36,85%, where as the optical density showed an average of 29,33 pixels. Cytophotometric expression of Caspase-3 was observed in a total of 22 slides, presenting an average labeling index of 87,71% and optical density of 60,74 pixels. When comparing the labeling indexes of both of the tumoral markers Ki-67 and Caspase-3 concerning the 14 slides analyzed, a significant difference (P<0,001

Lymphogenous metastasis to the transverse colon that originated from signet-ring cell gastric cancer: A case report and review of the literature.

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Sonoda, Hirofumi; Kawai, Kazushige; Yamaguchi, Hironori; Murono, Koji; Kaneko, Manabu; Nishikawa, Takeshi; Otani, Kensuke; Sasaki, Kazuhito; Yasuda, Koji; Tanaka, Toshiaki; Kiyomatsu, Tomomichi; Hata, Keisuke; Nozawa, Hiroaki; Ishihara, Soichiro; Aikou, Susumu; Yamashita, Hiroharu; Ushiku, Tetsuo; Seto, Yasuyuki; Fukayama, Masashi; Watanabe, Toshiaki

2017-12-01

Metastases to the colon are rare and a high-frequency primary region is the stomach. In cases of metastases to the colon, the morphological type of the metastatic region is mostly the infiltrating type of poorly differentiated or undifferentiated adenocarcinoma with lymph and blood vessel invasion. A case of cancer metastasis to the transverse colon that originated from advanced gastric cancer, which shows the difficulties in the precise diagnosis of metastases to the colon, is presented. In the present case, the gastric carcinoma was determined to be an advanced infiltrative ulcerative adenocarcinoma and the colon carcinoma was determined to be a superficial depressed adenocarcinoma. After surgery, the colon carcinoma was diagnosed as a metastatic adenocarcinoma from gastric adenocarcinoma with high invasion of vessels, by immunohistopathological analysis of CK7, CK20, p53 and HER-2. In this report, previously reported cases of metastases to the colon from gastric cancer were reviewed and their morphological characteristics were analyzed. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Result of surgical therapy in esophagogastric junction adenocarcinoma

International Nuclear Information System (INIS)

Shirinzadeh, A.; Fakhrjoo, E.

2007-01-01

To assess the outcome of surgical therapy and choice of surgical strategy for patients with adenocarcinoma of the gastroesophageal junction. Between February 1989 and January 2005 during 16 years, 335 patients (65 female, 270 male, mean age 56 years) with esophagogastric junction adenocarcinoma underwent surgical operation. The choice of surgical approach was based on the anatomical location of the tumor mass. Outcome of surgery, histopathologic characteristics, demographic data and long term survival rates were compared among three types of tumor defined as follows. Type I: Adenocarcinoma of the distal esophagus which infiltrates the esophagogastric junction from above. Type II: True carcinoma of the cardia arising immediately at the esophagogastric junction. Type III: Subcardial gastric carcinoma that infiltrates the esophagogastric junction and distal esophagus from below. Of the 335 patients undergoing resection, 110 (33%) had type I, 96 (28%) had type II, and 129 (39%) had type III. The preponderance of the male sex and the prevalence of metaplasia in distal esophagus decreased from type I to type III tumors (P<0.01). The prevalence of undifferentiated tumors increased from type I to type III tumors (P<0.01). Esophagectomy with resection of the proximal stomach for type I and extended total gastrectomy with transhiatal resection of the distal esophagus for type II and III were the primary procedures. The mean number of removed lymph node was higher in type III and II compared to type I tumors. The overall postoperative 30-day mortality was 8.4%. The death rate in transthoracic esophagectomy was higher than with extended total gastrectomy. The classification of adenocarcinoma of the esophagogastric junction into type I, II and III tumors helps in the selection of surgical approach. Type I tumors are approached as distal esophageal cancer. Type III tumors are a special form of gastric cancer and treated as a gastric cancer. The relation of type II tumors to

Evidence that expression of a mutated p53 gene attenuates apoptotic cell death in human gastric intestinal-type carcinomas in vivo.

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Ishida, M; Gomyo, Y; Ohfuji, S; Ikeda, M; Kawasaki, H; Ito, H

1997-05-01

To examine in vivo the validity of the results of experiments in vitro, we analyzed the relationship between p53 gene status and apoptotic cell death of human gastric intestinal-type adenocarcinomas. Surgical specimens were classified into two categories: 18 gastric cancers with nuclear p53 protein (A), and 17 gastric cancers without nuclear p53 protein (B). Polymerase chain reaction-single strand conformation polymorphism disclosed a shifted band that corresponded to a mutation in the p53 gene in 13 cases (72%) in category A and 3 cases (18%) in category B, the frequency being significantly higher in the former (P terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL). The TUNEL index [TI; (the number of TUNEL-positive apoptotic cells/the total number of tumor cells) x 100] was 3.8 +/- 1.4% in category A and 4.9 +/- 1.2% in category B, the value being significantly lower in the former (P gastric cancer, in accordance with the previous in vitro finding that p53 gene mutation provides a possible selective advantage for tumor cell proliferation, and (2) apoptosis is related not only to expression of p53 and the stage of the cell cycle, but also to p53-independent and cell cycle-independent events.

IMMUNOHISTOCHEMICAL EXPRESSION OF HER2 IN ADENOCARCINOMA OF THE STOMACH

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Diego Michelon DE CARLI

2015-06-01

Full Text Available Background Worldwide, gastric cancer is the fourth cancer in incidence and the second most common cause of cancer death. Gastric cancer is asymptomatic in the early stages and very often diagnosed at advanced stages, determining a dismal prognosis. Expression of the HER2 gene has been identified in about 20% of gastric cancer cases, and its hyper-expression is associated with poor prognosis. Objective To investigate HER2 immunohistochemical expression in gastric adenocarcinoma and its relationship to the histological type and anatomic location. Methods A cross-sectional retrospective study analyzed the immunohistochemical expression of HER2 in a sample of 48 specimens of gastric cancer. Immunohistochemical analysis were performed using avidin-biotin-peroxidase method with C-erb B2 (clone EP1045Y, as a primary antibody (Biocare Medical, USA. Standardized gastric adenocarcinoma‘s HER2 expression criteria has been used in the analysis of samples. Results There were seven cases with reactivity for HER2. Five were of intestinal-type while two cases were of mixed-type in which the expression occurred in the intestinal component. It was identified a significant association of HER2 expression in the intestinal subtype of gastric adenocarcinoma (P=0.003. Regarding the anatomical site, HER2 was positive in only one (16.6% of the six proximal cases and six (14.28% of the 42 distal cases (P=0.88. Conclusion HER2 immunoexpression was identified in 14.6% of the samples, and the expression was significantly associated to Lauren’s intestinal subtype.

EXPRESSION OF E-CADHERIN AND WNT PATHWAY PROTEINS BETACATENIN, APC, TCF-4 AND SURVIVIN IN GASTRIC ADENOCARCINOMA: CLINICAL AND PATHOLOGICAL IMPLICATION.

Science.gov (United States)

Lins, Rodrigo Rego; Oshima, Celina Tizuko Fujiyama; Oliveira, Levindo Alves de; Silva, Marcelo Souza; Mader, Ana Maria Amaral Antonio; Waisberg, Jaques

2016-01-01

Gastric cancer is the fifth most frequent cancer and the third most common cause of cancer-related deaths worldwide.It has been reported that Wnt/ betacatenin pathway is activated in 30-50% of these tumors. However,the deregulation of this pathway has not been fully elucidated. To determine the expression of E-cadherin, betacatenin, APC, TCF-4 and survivin proteins in gastric adenocarcinoma tissues and correlate with clinical and pathological parameters. Seventy-one patients with gastric adenocarcinoma undergoing gastrectomy were enrolled. The expression of E-cadherin, betacatenin, APC, TCF-4 and survivin proteins was detected by immunohistochemistryand related to the clinical and pathological parameters. The expression rates of E-cadherin in the membrane was 3%; betacatenin in the cytoplasm and nucleus were 23,4% and 3,1% respectively; APC in the cytoplasm was 94,6%; TCF-4 in the nucleus was 19,4%; and survivin in the nucleus 93,9%. The expression rate of E-cadherin was correlated with older patients (p=0,007), while betacatenin with tumors citoplasma e 3,1% no núcleo; APC em 94,6% no citoplasma; TCF-4 em19,4% no núcleo; e survivina em 93,9% no núcleo. Houve relação entre expressão da proteína E-caderina com a idade mais avançada (p=0,007); betacatenina com tumores <5 cm de diâmetro (p=0,041);APC com tumores proximais (p=0,047); e TCF-4 com tipo difuso da classificação de Lauren (p=0,017) e com o grau de penetração tumoral (p=0,002). A via Wnt/betacatenina não está envolvida na carcinogênese gástrica. Porém, a frequência elevada de survivina permite sugerir que outras vias sinalizadoras devam estar envolvidas na transformação do tecido gástrico.

SSAT State-of-the-Art Conference: Current Surgical Management of Gastric Tumors.

Science.gov (United States)

Norton, Jeffrey A; Kim, Teresa; Kim, Joseph; McCarter, Martin D; Kelly, Kaitlyn J; Wong, Joyce; Sicklick, Jason K

2018-01-01

The current era of gastric surgery is marked by low morbidity and mortality rates, innovative strategies to approach resections with a minimally invasive fashion or hyperthermic intraperitoneal chemotherapy (HIPEC), as well as improved understanding of the biology of sporadic and hereditary stromal, neuroendocrine, and epithelial malignancies. In 2017, the Society for Surgery of the Alimentary Tract convened a State-of-the-Art Conference on Current Surgical Management of Gastric Tumors with both international experts and emerging leaders in the field of gastric surgery. Martin D. McCarter, MD of the University of Colorado discussed the current management of gastric gastrointestinal stromal tumors (GIST). Kaitlyn J. Kelly, MD of the University of California, San Diego discussed the management of gastric carcinoid tumors. Jeffrey A. Norton of Stanford University discussed recent advances in the management of gastric adenocarcinoma including a focus on hereditary diffuse gastric cancer (HDGC). Joseph Kim, MD of Stony Brook University discussed a systematic approach to minimally invasive gastrectomy for cancer. Joyce Wong, MD of Pennsylvania State University discussed the role for cytoreductive surgery (CRS) and HIPEC for gastric adenocarcinoma. This review provides gastrointestinal surgeons with a concise update on the current surgical management of gastric tumors.

Reduction of hexavalent chromium by fasted and fed human gastric fluid. II. Ex vivo gastric reduction modeling

Energy Technology Data Exchange (ETDEWEB)

Kirman, Christopher R., E-mail: ckirman@summittoxicology.com [Summit Toxicology, Orange Village, OH, 44022 (United States); Suh, Mina, E-mail: msuh@toxstrategies.com [ToxStrategies, Inc., Mission Viejo, CA, 92692 (United States); Hays, Sean M., E-mail: shays@summittoxicology.com [Summit Toxicology, Allenspark, CO, 8040 (United States); Gürleyük, Hakan, E-mail: hakan@brooksrand.com [Brooks Applied Labs, Bothell, WA, 98011 (United States); Gerads, Russ, E-mail: russ@brooksrand.com [Brooks Applied Labs, Bothell, WA, 98011 (United States); De Flora, Silvio, E-mail: sdf@unige.it [Department of Health Sciences, University of Genoa, 16132 Genoa (Italy); Parker, William, E-mail: william.parker@duke.edu [Duke University Medical Center, Department of Surgery, Durham, NC, 27710 (United States); Lin, Shu, E-mail: shu.lin@duke.edu [Duke University Medical Center, Department of Surgery, Durham, NC, 27710 (United States); Haws, Laurie C., E-mail: lhaws@toxstrategies.com [ToxStrategies, Inc., Katy, TX, 77494 (United States); Harris, Mark A., E-mail: mharris@toxstrategies.com [ToxStrategies, Inc., Austin, TX, 78751 (United States); Proctor, Deborah M., E-mail: dproctor@toxstrategies.com [ToxStrategies, Inc., Mission Viejo, CA, 92692 (United States)

2016-09-01

To extend previous models of hexavalent chromium [Cr(VI)] reduction by gastric fluid (GF), ex vivo experiments were conducted to address data gaps and limitations identified with respect to (1) GF dilution in the model; (2) reduction of Cr(VI) in fed human GF samples; (3) the number of Cr(VI) reduction pools present in human GF under fed, fasted, and proton pump inhibitor (PPI)-use conditions; and (4) an appropriate form for the pH-dependence of Cr(VI) reduction rate constants. Rates and capacities of Cr(VI) reduction were characterized in gastric contents from fed and fasted volunteers, and from fasted pre-operative patients treated with PPIs. Reduction capacities were first estimated over a 4-h reduction period. Once reduction capacity was established, a dual-spike approach was used in speciated isotope dilution mass spectrometry analyses to characterize the concentration-dependence of the 2nd order reduction rate constants. These data, when combined with previously collected data, were well described by a three-pool model (pool 1 = fast reaction with low capacity; pool 2 = slow reaction with higher capacity; pool 3 = very slow reaction with higher capacity) using pH-dependent rate constants characterized by a piecewise, log-linear relationship. These data indicate that human gastric samples, like those collected from rats and mice, contain multiple pools of reducing agents, and low concentrations of Cr(VI) (< 0.7 mg/L) are reduced more rapidly than high concentrations. The data and revised modeling results herein provide improved characterization of Cr(VI) gastric reduction kinetics, critical for Cr(VI) pharmacokinetic modeling and human health risk assessment. - Highlights: • SIDMS allows for measurement of Cr(VI) reduction rate in gastric fluid ex vivo • Human gastric fluid has three reducing pools • Cr(VI) in drinking water at < 0.7 mg/L is rapidly reduced in human gastric fluid • Reduction rate is concentration- and pH-dependent • A refined PK

Characterizing lamina propria of human gastric mucosa by multiphoton microscopy

Energy Technology Data Exchange (ETDEWEB)

Liu, Y C; Yang, H Q; Zhuo, S M [Institute of Laser and Optoelectronics Technology, Fujian Provincial Key Laboratory for Photonics Technology, Key Laboratory of OptoElectronic Science and Technology for Medicine of Ministry of Education, Fujian Normal University, Fuzhou 350007 (China); Chen, G; Chen, J X [Department of Pathology, Fujian Provincial Tumor Hospital, Fuzhou, 350014 (China); Yan, J, E-mail: chenjianxin@fjnu.edu.cn, E-mail: ynjun@yahoo.com [Department of Surgery, Fujian Provincial Tumor Hospital, Fuzhou, 350014 (China)

2011-01-01

Lamina propria (LP) of gastric mucosa plays an important role in progression of gastric cancer because of the site at where inflammatory reactions occur. Multiphoton imaging has been recently employed for microscopic examination of intact tissue. In this paper, using multiphoton microscopy (MPM) based on two-photon excited fluorescence (TPEF) and second harmonic generation (SHG), high resolution multiphoton microscopic images of lamina propria (LP) are obtained in normal human gastric mucosa at excitation wavelength {lambda}{sub ex} = 800 nm. The main source of tissue TPEF originated from the cells of gastric glands, and loose connective tissue, collagen, produced SHG signals. Our results demonstrated that MPM can be effective for characterizing the microstructure of LP in human gastric mucosa. The findings will be helpful for diagnosing and staging early gastric cancer in the clinics.

Characterizing lamina propria of human gastric mucosa by multiphoton microscopy

Science.gov (United States)

Liu, Y. C.; Yang, H. Q.; Chen, G.; Zhuo, S. M.; Chen, J. X.; Yan, J.

2011-01-01

Lamina propria (LP) of gastric mucosa plays an important role in progression of gastric cancer because of the site at where inflammatory reactions occur. Multiphoton imaging has been recently employed for microscopic examination of intact tissue. In this paper, using multiphoton microscopy (MPM) based on two-photon excited fluorescence (TPEF) and second harmonic generation (SHG), high resolution multiphoton microscopic images of lamina propria (LP) are obtained in normal human gastric mucosa at excitation wavelength λex = 800 nm. The main source of tissue TPEF originated from the cells of gastric glands, and loose connective tissue, collagen, produced SHG signals. Our results demonstrated that MPM can be effective for characterizing the microstructure of LP in human gastric mucosa. The findings will be helpful for diagnosing and staging early gastric cancer in the clinics.

Radiation therapy for gastric cancer

International Nuclear Information System (INIS)

Dobelbower, R.R.; Bagne, F.; Ajlouni, M.I.; Milligan, A.J.

1988-01-01

Adenocarcinoma of the stomach is a moderately radioresponsive neoplasm. Attempts to treat patients with unresectable disease with external beam radiation therapy alone have generally failed because of problems with tumor localization and adequate dose delivery as well as the inherent radioresponsiveness of the gastric mucosa and the organs intimately related to the stomach. Combining external beam therapy and chemotherapy (acting as a systemic agent and as a radiosensitizer) seems to be of some (albeit limited) benefit in the management of unresectable adenocarcinoma of the stomach. Optimum combinations of radiation therapy, chemotherapy, and radiation sensitizers in this situation remain to be determined. The authors discuss strides which have been made in the treatment of gastric cancer. They also address the unanswered clinical questions which remain regarding the use of radiation therapy in the treatment of this highly lethal disease

Effects of EGFR Inhibitor on Helicobacter pylori Induced Gastric Epithelial Pathology in Vivo

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Philip A. Robinson

2013-10-01

Full Text Available Helicobacter pylori transactivates the Epidermal Growth Factor Receptor (EGFR and predisposes to gastric cancer development in humans and animal models. To examine the importance of EGFR signalling to gastric pathology, this study investigated whether treatment of Mongolian gerbils with a selective EGFR tyrosine kinase inhibitor, EKB-569, altered gastric pathology in chronic H. pylori infection. Gerbils were infected with H. pylori and six weeks later received either EKB-569-supplemented, or control diet, for 32 weeks prior to sacrifice. EKB-569-treated H. pylori-infected gerbils had no difference in H. pylori colonisation or inflammation scores compared to infected animals on control diet, but showed significantly less corpus atrophy, mucous metaplasia and submucosal glandular herniations along with markedly reduced antral and corpus epithelial proliferation to apoptosis ratios. EKB-569-treated infected gerbils had significantly decreased abundance of Cox-2, Adam17 and Egfr gastric transcripts relative to infected animals on control diet. EGFR inhibition by EKB-569 therefore reduced the severity of pre-neoplastic gastric pathology in chronically H. pylori-infected gerbils. EKB-569 increased gastric epithelial apoptosis in H. pylori-infected gerbils which counteracted some of the consequences of increased gastric epithelial cell proliferation. Similar chemopreventative strategies may be useful in humans who are at high risk of developing H.pylori-induced gastric adenocarcinoma.

Translating Developmental Principles to Generate Human Gastric Organoids

OpenAIRE

Alexandra K. Eicher; H. Matthew Berns; James M. Wells

2018-01-01

Gastric diseases, including peptic ulcer disease and gastric cancer, are highly prevalent in human beings. Despite this, the cellular biology of the stomach remains poorly understood relative to other gastrointestinal organs such as the liver, intestine, and colon. In particular, little is known about the molecular basis of stomach development and the differentiation of gastric lineages. Although animal models are useful for studying gastric development, function, and disease, there are major...

Comparação dos diagnósticos histológico e molecular do Helicobacter pylori em lesões benignas e adenocarcinomas gástricos

OpenAIRE

César, Ana Cristina Gobbo; Cury, Patrícia Maluf; Payão, Spencer Luiz Marques; Liberatore, Paula Rahal; Silva, Ana Elizabete

2005-01-01

Helicobacter pylori colonization is associated with chronic gastritis, peptic ulcers, intestinal metaplasia, adenocarcinoma and lymphoma of the stomach. The objective of this study was to compare the results of the routinely used histology with molecular diagnosis for the detection of H. pylori. Eighty samples from gastric lesions (chronic gastritis, atrophic gastritis, gastric ulcer, and intestinal metaplasia), 18 gastric adenocarcinoma and 10 normal mucosa H. pylori-negative (control) sampl...

Murine Models of Gastric Corpus PreneoplasiaSummary

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Christine P. Petersen

2017-01-01

Full Text Available Intestinal-type gastric adenocarcinoma evolves in a field of pre-existing metaplasia. Over the past 20 years, a number of murine models have been developed to address aspects of the physiology and pathophysiology of metaplasia induction. Although none of these models has achieved true recapitulation of the induction of adenocarcinoma, they have led to important insights into the factors that influence the induction and progression of metaplasia. Here, we review the pathologic definitions relevant to alterations in gastric corpus lineages and classification of metaplasia by specific lineage markers. In addition, we review present murine models of the induction and progression of spasmolytic polypeptide (TFF2–expressing metaplasia, the predominant metaplastic lineage observed in murine models. These models provide a basis for the development of a broader understanding of the physiological and pathophysiological roles of metaplasia in the stomach. Keywords: SPEM, Intestinal Metaplasia, Gastric Cancer, TFF2, Chief Cell, Hyperplasia

Molecular Mechanism of Gastric Carcinogenesis in Helicobacter pylori-Infected Rodent Models

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Takeshi Toyoda

2014-06-01

Full Text Available Since the discovery of Helicobacter pylori (H. pylori, many efforts have been made to establish animal models for the investigation of the pathological features and molecular mechanisms of gastric carcinogenesis. Among the animal models, Mongolian gerbils and mice are particularly useful for the analysis of H. pylori-associated inflammatory reactions and gastric cancer development. Inhibitors of oxidative stress, cyclooxygenase-2 (COX-2 and nuclear factor-κB, exert preventive effects on chronic gastritis and the development of adenocarcinomas in H. pylori-infected gerbils. Genetically-modified mouse models, including transgenic and knockout mice, have also revealed the importance of p53, COX-2/prostaglandin, Wnt/β-catenin, proinflammatory cytokines, gastrin and type III mucin in the molecular mechanisms of gastric carcinogenesis. Microarray technology is available for comprehensive gene analysis in the gastric mucosa of mouse models, and epigenetics, such as DNA methylation, could be an alternative approach to correlate the observations in animal models with the etiology in humans.

Bone metastases from gastric cancer

International Nuclear Information System (INIS)

Seto, Mikito; Tonami, Norihisa; Koizumi, Kiyoshi; Sui, Osamu; Hisada, Kinichi

1983-01-01

We have studied bone scintigrams in 60 patients with gastric cancer. Of these 60 patients, bone metastases were found in 15 patients (25 %). There were no evidence of bone metastases in polypoid lesions, cancers of the antrum, carcinomas in situ, advanced cancers without invasion to serosa, cancer with N 0 or N 1 regional lymph node metastases, highly deferenciated adenocarcinomas and papillary adenocarcinomas. On the contrary, high rates of bone metastases were seen in cancers of the corpus, advanced cancers with invasion to neighbouring structures and tubular adenocarcinomas. Of these 15 patients with bone metastasis, 3 patients showed very similar clinical features and the findings of ''diffuse bone metastases on bone scintigrams.'' Cancer of the antrum showed high rates of liver metastases, while cancers of the corpus showed high rates of bone stastases. Sixty percent of the patients with bone metastases did not have liver metastases and there seemed to be no significant relationship between liver metastases and bone metastases. From these results we suppose that non-portal tract through the vertebral venous plexus instead of portal tract may be the other route of bone metastases from gastric cancer. (author)

Synchronous colon and gastric advanced carcinomas

International Nuclear Information System (INIS)

Giuliani, A.; Demoro, M.; Corona, M.; Di Bari, M.; Ricciardulli, T.; Galati, G.; Ciardi, A.

2005-01-01

An unusual case of advanced synchronous colon and gastric carcinoma is described. A 36 year old female was admitted to our Department with a stenosing right colon cancer diagnosed at endoscopy which was performed for lower crampy abdominal pain and gross blood in the stool. Multiple colon polyps, distal to the tumor, were also detected. On preoperative abdominal computed tomography, a stenosing right colon cancer, without evidence of abdominal diffusion, was confirmed. At laparotomy, in addition to colon cancer, an antral gastric cancer was incidentally found. En bloc hemi gastrectomy and subtotal colectomy were performed. Digestive continuity was restored by gastrojejunal and ileosigmoid anastomoses. At histology, a poorly differentiated gastric adenocarcinoma with signet ring-cell component (pT2, pN0; stage IB) and a moderately differentiated colon adenocarcinoma with a tubulovillous component (pT3, pN1; stage III, Stage Dukes C) were revealed. Both tumors showed a low expression of p53 and c-erb2 oncoproteins. No genetic defect was identified in the APC and MMR genes. The patient is alive, without recurrence, two years after the operation

Human gastric cancer, Helicobacter pylori and bracken carcinogens: A connecting hypothesis.

Science.gov (United States)

Oliveros-Bastidas, Alberto; Calcagno-Pissarelli, María Pía; Naya, Marlene; Ávila-Núñez, Jorge Luis; Alonso-Amelot, Miguel E

2016-03-01

Long term infection of Helicobacter pylori (Hp) virulent strains is a key factor in the genesis of human gastric cancer, and so are certain dietary proinflammatory and genotoxic compounds. Carcinogenic bracken fern (Pteridium spp.) is one of these. Toxins from this plant are consumed as bracken culinary preparations, through milk and meat of bracken-exposed livestock, and drain waters from bracken swards. Bracken toxin ptaquiloside (PtQ), a suspected human carcinogen, elicits complex responses in animals leading to death. PtQ and Hp might cooperate in gastric pathologies. This paper presents an hypothesis on PtQ-Hp association leading to the enhancement of carcinogenesis in the human gastric environment that might explain the high gastric cancer incidence and death rates among Hp-infected people living in bracken zones at two levels: (1) The macroscopic scale comprising the flow of PtQ in the human diet. (2) the microscopic scale encompassing (A) gastric luminal medium; (B) gastric mucus structure and mucin degradation elicited by Hp; (C) bacterial pH gradient modification of the gastric mucosa that favors PtQ survival and its penetration into epithelial tissue; (D) combined PtQ/Hp effects on gastric immune and inflammatory responses; (E) PtQ-Hp complementary activity at selected cell signaling cascades and genome disturbance. Copyright © 2015 Elsevier Ltd. All rights reserved.

The number of Foxp3-positive regulatory T cells is increased in Helicobacter pylori gastritis and gastric cancer.

Science.gov (United States)

Jang, Tae Jung

2010-01-15

Helicobacter pylori (H. pylori) colonization induces vigorous innate and specific immune responses; however, the infection is not removed, a state of chronic active gastritis persists for life if untreated. Recent studies have shown that CD4(+) CD25(+) Foxp3-positive regulatory T cells (Tregs) suppress the immune response to H. pylori. Persistent H. pylori-associated gastritis is closely associated with gastric carcinogenesis. We investigated the number of Tregs in the context of H. pylori colonization in chronic gastritis, examined the relationship between it and histopathological findings and compared it with that of gastric dysplasia and adenocarcinoma. This study was based on the analysis of gastric biopsy specimens from 126 cases of H. pylori-associated gastritis, 16 cases of H. pylori-negative gastritis, 17 cases of gastric dysplasia, and 25 cases of gastric adenocarcinoma. The number of Tregs was elevated in H. pylori-associated gastritis, where it was positively correlated with the grade of chronic inflammation and the number of lymphoid follicles. It was significantly elevated in adenocarcinomas compared to chronic gastritis and gastric dysplasia. In summary, the number of Tregs is increased in H. pylori-associated gastritis and gastric cancer. Copyright 2009 Elsevier GmbH. All rights reserved.

Fibulin-1 functions as a prognostic factor in lung adenocarcinoma.

Science.gov (United States)

Cui, Yuan; Liu, Jian; Yin, Hai-Bing; Liu, Yi-Fei; Liu, Jun-Hua

2015-09-01

Fibulin-1 is a member of the fibulin gene family, characterized by tandem arrays of epidermal growth factor-like domains and a C-terminal fibulin-type module. Fibulin-1 plays important roles in a range of cellular functions including morphology, growth, adhesion and mobility. It acts as a tumor suppressor gene in cutaneous melanoma, prostate cancer and gastric cancer. However, whether fibulin-1 also acts as a tumor suppressor gene in lung adenocarcinoma remains unknown. We also determined the association of fibulin-1 expression with various clinical and pathological parameters, which would show its potential role in clinical prognosis. We investigated and followed up 140 lung adenocarcinoma patients who underwent lung resection without pre- and post-operative systemic chemotherapy at the Affiliated Hospital of Nantong University from 2009 to 2013. Western blot assay and immunohistochemistry were used to evaluate the expression of fibulin-1 in lung adenocarcinoma tissues. We then analyzed the correlations between fibulin-1 expression and clinicopathological variables as well as the patients' overall survival rate. Both western blot assay and immunohistochemistry demonstrated that the level of fibulin-1 was downregulated in human lung adenocarcinoma tissues compared with that of normal lung tissues. Fibulin-1 expression significantly correlated with histological differentiation (P = 0.046), clinical stage (P< 0.01), lymph node status (P = 0.038) and expression of Ki-67 (P = 0.013). More importantly, multivariate analysis revealed that fibulin-1 was an independent prognostic marker for lung adenocarcinoma, and high expression of fibulin-1 was significantly associated with better prognosis of lung adenocarcinoma patients. The results supported our hypothesis that fibulin-1 can act as a prognostic factor in lung adenocarcinoma progression. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Study of gastric cancer samples using terahertz techniques

Science.gov (United States)

Wahaia, Faustino; Kasalynas, Irmantas; Seliuta, Dalius; Molis, Gediminas; Urbanowicz, Andrzej; Carvalho Silva, Catia D.; Carneiro, Fatima; Valusis, Gintaras; Granja, Pedro L.

2014-08-01

In the present work, samples of healthy and adenocarcinoma-affected human gastric tissue were analyzed using transmission time-domain THz spectroscopy (THz-TDS) and spectroscopic THz imaging at 201 and 590 GHz. The work shows that it is possible to distinguish between normal and cancerous regions in dried and paraffin-embedded samples. Plots of absorption coefficient α and refractive index n of normal and cancer affected tissues, as well as 2-D transmission THz images are presented and the conditions for discrimination between normal and affected tissues are discussed.

Contribution of H. pylori and smoking trends to US incidence of intestinal-type noncardia gastric adenocarcinoma: a microsimulation model.

Science.gov (United States)

Yeh, Jennifer M; Hur, Chin; Schrag, Deb; Kuntz, Karen M; Ezzati, Majid; Stout, Natasha; Ward, Zachary; Goldie, Sue J

2013-01-01

Although gastric cancer has declined dramatically in the US, the disease remains the second leading cause of cancer mortality worldwide. A better understanding of reasons for the decline can provide important insights into effective preventive strategies. We sought to estimate the contribution of risk factor trends on past and future intestinal-type noncardia gastric adenocarcinoma (NCGA) incidence. We developed a population-based microsimulation model of intestinal-type NCGA and calibrated it to US epidemiologic data on precancerous lesions and cancer. The model explicitly incorporated the impact of Helicobacter pylori and smoking on disease natural history, for which birth cohort-specific trends were derived from the National Health and Nutrition Examination Survey (NHANES) and National Health Interview Survey (NHIS). Between 1978 and 2008, the model estimated that intestinal-type NCGA incidence declined 60% from 11.0 to 4.4 per 100,000 men, <3% discrepancy from national statistics. H. pylori and smoking trends combined accounted for 47% (range = 30%-58%) of the observed decline. With no tobacco control, incidence would have declined only 56%, suggesting that lower smoking initiation and higher cessation rates observed after the 1960s accelerated the relative decline in cancer incidence by 7% (range = 0%-21%). With continued risk factor trends, incidence is projected to decline an additional 47% between 2008 and 2040, the majority of which will be attributable to H. pylori and smoking (81%; range = 61%-100%). Limitations include assuming all other risk factors influenced gastric carcinogenesis as one factor and restricting the analysis to men. Trends in modifiable risk factors explain a significant proportion of the decline of intestinal-type NCGA incidence in the US, and are projected to continue. Although past tobacco control efforts have hastened the decline, full benefits will take decades to be realized, and further discouragement of smoking and reduction of

Fiber-optic Raman spectroscopy for in vivo diagnosis of gastric dysplasia.

Science.gov (United States)

Wang, Jianfeng; Lin, Kan; Zheng, Wei; Ho, Khek Yu; Teh, Ming; Yeoh, Khay Guan; Huang, Zhiwei

2016-06-23

This study aims to assess the clinical utility of a rapid fiber-optic Raman spectroscopy technique developed for enhancing in vivo diagnosis of gastric precancer during endoscopic examination. We have developed a real-time fiber-optic Raman spectroscopy system capable of simultaneously acquiring both fingerprint (FP) (i.e., 800-1800 cm(-1)) and high-wavenumber (HW) (i.e., 2800-3600 cm(-1)) Raman spectra from gastric tissue in vivo at endoscopy. A total of 5792 high-quality in vivo FP/HW Raman spectra (normal (n = 5160); dysplasia (n = 155), and adenocarcinoma (n = 477)) were acquired in real-time from 441 tissue sites (normal (n = 396); dysplasia (n = 11), and adenocarcinoma (n = 34)) of 191 gastric patients (normal (n = 172); dysplasia (n = 6), and adenocarcinoma (n = 13)) undergoing routine endoscopic examinations. Partial least squares discriminant analysis (PLS-DA) together with leave-one-patient-out cross validation (LOPCV) were implemented to develop robust spectral diagnostic models. The FP/HW Raman spectra differ significantly between normal, dysplasia and adenocarcinoma of the stomach, which can be attributed to changes in proteins, lipids, nucleic acids, and the bound water content. PLS-DA and LOPCV show that the fiber-optic FP/HW Raman spectroscopy provides diagnostic sensitivities of 96.0%, 81.8% and 88.2%, and specificities of 86.7%, 95.3% and 95.6%, respectively, for the classification of normal, dysplastic and cancerous gastric tissue, superior to either the FP or HW Raman techniques alone. Further dichotomous PLS-DA analysis yields a sensitivity of 90.9% (10/11) and specificity of 95.9% (380/396) for the detection of gastric dysplasia using FP/HW Raman spectroscopy, substantiating its clinical advantages over white light reflectance endoscopy (sensitivity: 90.9% (10/11), and specificity: 51.0% (202/396)). This work demonstrates that the fiber-optic FP/HW Raman spectroscopy technique has great promise for enhancing in vivo diagnosis of gastric

Dietary N-nitroso compounds, endogenous nitrosation, and the risk of esophageal and gastric cancer subtypes in the Netherlands Cohort Study.

Science.gov (United States)

Keszei, András P; Goldbohm, R Alexandra; Schouten, Leo J; Jakszyn, Paula; van den Brandt, Piet A

2013-01-01

Dietary N-nitroso compounds and endogenous nitrosation are important carcinogenic factors, but human evidence of their role is scarce for esophageal cancer and inconsistent for gastric cancer. We studied the relation between risks of esophageal and gastric cancer subtypes and dietary intake of N-nitrosodimethylamine, heme iron, nitrite, and nitrate in the Netherlands Cohort Study. A total of 120,852 men and women aged 55-69 y were recruited in 1986, and diet, based on a 150-item food-frequency questionnaire, and other risk factors were assessed. The cohort was followed for 16.3 y, and 110 esophageal squamous cell carcinoma (ESCC), 151 esophageal adenocarcinoma, 166 gastric cardia adenocarcinoma, and 497 gastric noncardia adenocarcinoma (GNCA) cases were analyzed along with 4032 subcohort members in a case-cohort analysis. Positive associations were observed between N-nitrosodimethylamine intake and ESCC risk (HR for 0.1-μg/d increase in intake: 1.15; 95% CI: 1.05, 1.25; P-trend = 0.01 based on tertiles of intake) and GNCA risk (1.06; 95% CI: 1.01, 1.10; P-trend = 0.09) in men. ESCC risk was associated with nitrite intake (HR for 0.1-mg/d increase: 1.19; 95% CI: 1.05, 1.36; P-trend = 0.06) and heme-iron intake (HR for 1-mg/d increase: 1.83; 95% CI: 0.98, 3.39; P-trend = 0.03). Among women, exposure levels were lower, and we found no convincing positive associations. These results suggest that N-nitroso compounds may influence the risk of ESCC in men, but there are no clear associations for other esophageal and gastric subtypes.

Metástasis mandibular de adenocarcinoma gástrico: Presentación de un caso Mandibular metastases of gastric adenocarcinoma: A case report

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J. Ferreras Granado

2007-10-01

Full Text Available Los tumores malignos de la cavidad oral y mandíbula representan aproximadamente un 5% de todas las neoplasias malignas del cuerpo, y sólo entre el 1 y el 4% son consideradas como metástasis. Tienen su localización más frecuente a nivel de la mandíbula (80%, fundamentalmente en la región molar. Las metástasis mandibulares, cuando aparecen, suelen tener su origen en tumores primarios que asientan en la mama, pulmón, riñón, tiroides, intestinos y próstata; y con menor frecuencia en el estómago, testículos y vesícula biliar. Suelen afectar a pacientes de edad avanzada (4ª-7ª décadas de la vida sin predilección por el sexo. El tratamiento en general es paliativo y pasa por el uso de la radioterapia, quimioterapia y hormonoterapia, reservando la cirugía para casos aislados. Describimos un caso de metástasis mandibular en un paciente adulto como primera manifestación clínica de un adenocarcinoma gástrico.Malignant tumors of the mouth and jaws represents approximately 5% of all malignant neoplasms in the body, and only 1-4% are considered to be metastatic. They are most frequently located in the mandible (80%, fundamentally in the molar region. Metastases to the jaws are usually from breast, lung, kidney, thyroid gland, intestines, and prostate gland; and less frequently from stomach, testes, and bladder. They are more frequent in elderly patients (between 4th and 7th decades with no gender differences. Treatment is usually palliative and based on the use of radiotherapy, chemotherapy andhormonal therapy. Surgery is only used in selected cases. A case of mandibular metastases as first sign of malignant disease of gastric adenocarcinoma is reported.

Gastric epithelioid haemangioendothelioma.

Science.gov (United States)

Tavares, A B; Almeida, A G; Viveiros, F A; Cidade, C N; Barbosa, J M

2011-05-10

Epithelioid haemangioendothelioma (EHE) is a rare tumour of vascular origin, characterised by celular proliferation, endotelial, epitelioid or hystiocitoid. It may develop in any organ, but it is more common in lung and liver. Surgery is the recommended treatment; however, in case of a potentially benign situation, an expectant attitude should be adopted. The case reports a 71-year-old female who underwent a laparotomy for a colonic adenocarcinoma. During surgery, a polypoid lesion in the dependency of the gastric wall was found incidentally, which was removed. Histopathology and immunohistochemical analysis confirmed the diagnosis of EHE. Gastric vascular neoplasms represent about 0.9-3.3% of all gastric tumours. Usually have a good prognosis, but due to the borderline biological behaviour of these tumours, it is important to have a detailed clinical evaluation at follow-up of these patients.

Self-expanding metal stents versus antrectomy for the palliative treatment of obstructive adenocarcinoma of the gastric antrum Prótesis metálicas autoexpandibles versus antrectomía en el tratamiento paliativo del adenocarcinoma obstructivo del antro gástrico

Directory of Open Access Journals (Sweden)

Juan Octavio Alonso-Larraga

2012-04-01

Full Text Available Background: gastric cancer patients are first diagnosed with an unresectable tumor in up to 40% of cases. Gastric outlet obstruction causes nausea, vomiting, dehydration and malnutrition. The aim of the study was to compare self-expanding metal stents to antrectomy and Roux-en Y gastrojejunostomy for palliation of obstructive adenocarcinoma of the gastric antrum. Methods: retrospective study in patients with obstructing cancer of the gastric antrum. Patients were divided into two groups: group A, underwent endoscopic placement of self-expanding metal stents and group B underwent surgical treatment with antrectomy and Roux-en Y gastrojejunostomy. Collected Data included: age, gender, performance status (Karnofsky's score, body mass index, histopathology, clinical stage (TNM classification, technical and clinical success of the procedure, time to oral intake, in-hospital stay, re-intervention rate, and complications related to the treatment and survival. Results: a total of 39 patients with gastric adenocarcinoma were included, 21 male and 18 female. Nineteen patients were assigned to group A and 20 patients to group B. There were no statistically significant differences between groups in regards to age, body mass index, Karnofsky's score and clinical stage. The technical and clinical success was similar for both groups. There was a statistically significant difference between groups favoring Self-expanding metal stent in time to oral intake (1 ± 0 vs. 4.9 ± 0.6 days, p = 0.0001 and in-hospital stay (0.94 ± 1.18 vs. 7.8 ± 7.7 days, p = 0.0005. We did not find statistically significant differences with regards to long-term survival. Conclusions: in patients with malignant gastric outlet obstruction due to gastric cancer, endoscopic palliation with self-expanding metal stents provide a shorter interval to oral intake, shorter in-hospital stay and lower rate of complications.Introducción: los pacientes con cáncer gástrico tienen un tumor

Survival after adjuvant chemoradiotherapy or surgery alone in resectable adenocarcinoma at the gastro-esophageal junction

DEFF Research Database (Denmark)

Kofoed, Steen Christian; Muhic, A; Jensen, Lene Bæksgaard

2012-01-01

Longterm survival after curative resection for adenocarcinoma at the gastro-esophageal junction (GEJ) range between 18% and 50%. In the pivotal Intergroup-0116 Phase III trial by Macdonald et all, adjuvant chemoradiotherapy improved both disease-free and overall survival in curatively resected pa...... patients with mainly gastric adenocarcinoma. We compared survival data for curatively resected patients with adeno-carcinoma solely at the gastro-esophageal junction (GEJ), treated with surgery alone or surgery and adjuvant chemoradio-therapy....

Gastric carcinoma originating from the heterotopic submucosal gastric gland treated by laparoscopy and endoscopy cooperative surgery

Science.gov (United States)

Imamura, Taisuke; Komatsu, Shuhei; Ichikawa, Daisuke; Kobayashi, Hiroki; Miyamae, Mahito; Hirajima, Shoji; Kawaguchi, Tsutomu; Kubota, Takeshi; Kosuga, Toshiyuki; Okamoto, Kazuma; Konishi, Hirotaka; Shiozaki, Atsushi; Fujiwara, Hitoshi; Ogiso, Kiyoshi; Yagi, Nobuaki; Yanagisawa, Akio; Ando, Takashi; Otsuji, Eigo

2015-01-01

Gastric carcinoma is derived from epithelial cells in the gastric mucosa. We reported an extremely rare case of submucosal gastric carcinoma originating from the heterotopic submucosal gastric gland (HSG) that was safely diagnosed by laparoscopy and endoscopy cooperative surgery (LECS). A 66-year-old man underwent gastrointestinal endoscopy, which detected a submucosal tumor (SMT) of 1.5 cm in diameter on the lesser-anterior wall of the upper gastric body. The tumor could not be diagnosed histologically, even by endoscopic ultrasound-guided fine-needle aspiration biopsy. Local resection by LECS was performed to confirm a diagnosis. Pathologically, the tumor was an intra-submucosal well differentiated adenocarcinoma invading 5000 μm into the submucosal layer. The resected tumor had negative lateral and vertical margins. Based on the Japanese treatment guidelines, additional laparoscopic proximal gastrectomy was curatively performed. LECS is a less invasive and safer approach for the diagnosis of SMT, even in submucosal gastric carcinoma originating from the HSG. PMID:26306144

KITENIN is associated with tumor progression in human gastric cancer.

Science.gov (United States)

Ryu, Ho-Seong; Park, Young-Lan; Park, Su-Jin; Lee, Ji-Hee; Cho, Sung-Bum; Lee, Wan-Sik; Chung, Ik-Joo; Kim, Kyung-Keun; Lee, Kyung-Hwa; Kweon, Sun-Seog; Joo, Young-Eun

2010-09-01

KAI1 COOH-terminal interacting tetraspanin (KITENIN) promotes tumor cell migration, invasion and metastasis in colon, bladder, head and neck cancer. The aims of current study were to evaluate whether KITENIN affects tumor cell behavior in human gastric cancer cell line and to document the expression of KITENIN in a well-defined series of gastric tumors, including complete long-term follow-up, with special reference to patient prognosis. To evaluate the impact of KITENIN knockdown on behavior of a human gastric cancer cell line, AGS, migration, invasion and proliferation assays using small-interfering RNA were performed. The expression of activator protein-1 (AP-1) target genes and AP-1 transcriptional activity were evaluated by reverse transcription-polymerase chain reaction (RT-PCR) and luciferase reporter assay. The expression of KITENIN and AP-1 target genes by RT-PCR and Western blotting or immunohistochemistry was also investigated in human gastric cancer tissues. The knockdown of KITENIN suppressed tumor cell migration, invasion and proliferation in AGS cells. The mRNA expression of matrix metalloproteinase-1 (MMP-1), MMP-3, cyclooxygenase-2 (COX-2), and CD44 was reduced by knockdown of KITENIN in AGS. AP-1 transcriptional activity was significantly decreased by knockdown of KITENIN in AGS cells. KITENIN expression was significantly increased in human cancer tissues at RNA and protein levels. Expression of MMP-1, MMP-3, COX-2 and CD44 were significantly increased in human gastric cancer tissues. Immunostaining of KITENIN was predominantly identified in the cytoplasm of cancer cells. Expression of KITENIN was significantly associated with tumor size, Lauren classification, depth of invasion, lymph node metastasis, tumor stage and poor survival. These results indicate that KITENIN plays an important role in human gastric cancer progression by AP-1 activation.

Endostar, a recombined humanized endostatin, enhances the radioresponse for human nasopharyngeal carcinoma and human lung adenocarcinoma xenografts in mice

International Nuclear Information System (INIS)

Wen Qinglian; Meng Maobin; Tu Lingli; Jia Li; Zhou Lin; Xu Yong; Lu You; Yang Bo

2009-01-01

The purpose of this paper is to determine the efficacy of combining radiation therapy with endostar, a recombined humanized endostatin, in human nasopharyngeal carcinoma and human lung adenocarcinoma xenografts. Tumor xenografts were established in the hind limb of male athymic nude mice (BALB/c-nu) by subcutaneous transplantation. The tumor-bearing mice were assigned into four treatment groups: sham therapy (control), endostar (20 mg/kg, once daily for 10 days), radiation therapy (6 Gray per day to 30 Gray, once a day for 1 week), and endostar plus radiation therapy (combination). The experiment was repeated and mice were killed at days 3, 6, and 10 after initiation therapy, and the tumor tissues and blood samples were collected to analyze the kinetics of antitumor, antiangiogenesis, and antivascularization responses of different therapies. In human nasopharyngeal carcinoma and human lung adenocarcinoma xenografts, endostar significantly enhanced the effects of tumor growth inhibition, endothelial cell and tumor cell apoptosis induction, and improved tumor cell hypoxia of radiation therapy. Histological analyses demonstrated that endostar plus radiation also induced a significant reduction in microvascular density, microvascular area, and vascular endothelial growth factor and matrix metalloproteinase-2 expression compared with radiation and endostar alone respectively. We concluded that endostar significantly sensitized the function of radiation in antitumor and antiangiogenesis in human nasopharyngeal carcinoma and human lung adenocarcinoma xenografts by increasing the apoptosis of the endothelial cell and tumor cell, improving the hypoxia of the tumor cell, and changing the proangiogenic factors. These data provided a rational basis for clinical practice of this multimodality therapy. (author)

Pembrolizumab, Capecitabine, and Radiation Therapy in Treating Patients With Mismatch-Repair Deficient and Epstein-Barr Virus Positive Gastric Cancer

Science.gov (United States)

2017-11-15

Epstein-Barr Virus Positive; Gastric Adenocarcinoma; Mismatch Repair Protein Deficiency; Stage IB Gastric Cancer AJCC v7; Stage II Gastric Cancer AJCC v7; Stage IIA Gastric Cancer AJCC v7; Stage IIB Gastric Cancer AJCC v7; Stage III Gastric Cancer AJCC v7; Stage IIIA Gastric Cancer AJCC v7; Stage IIIB Gastric Cancer AJCC v7; Stage IIIC Gastric Cancer AJCC v7

Murine models of H. pylori-induced gastritis and gastric adenocarcinoma.

Science.gov (United States)

Krueger, Sabine; Roessner, Albert; Kuester, Doerthe

2011-10-15

Laboratory mice have become one of the best animal species for mechanistic studies in gastrointestinal research. Their abundant genetic information, the way of causing carcinogenesis easily by transgenic and gene knockout techniques, limited effort in time and costs, and their practicability provide advantages over other animal models. Meanwhile, several murine practical models have been established for the investigation of the initiation, expansion, and progression of gastritis and gastric carcinoma, for assessing the effects of bacterial, genetic and environmental factors, and for evaluating therapeutic and preventive strategies in gastric diseases. This article gives a review of murine models of gastritis and gastric cancer, placing emphasis on the models associated with Helicobacter pylori infection and techniques used in our laboratory. We discuss matters of murine gastric anatomy, as well as techniques of infection, tissue preparation, and histology. Copyright © 2011 Elsevier GmbH. All rights reserved.

Minimal invasive gastric surgery: A systematic review

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Kirti Bushan

2015-01-01

Full Text Available Background: As an alternate to open surgery, laparoscopic gastrectomy (LG is currently being performed in many centers, and has gained a wide clinical acceptance. The aim of this review article is to compare oncologic adequacy and safety of LG with open surgery for gastric adenocarcinomas with respect to lymphadenectomy, short-term outcomes (postoperative morbidity and mortality and long-term outcome (5 years overall survival and disease-free survival. Materials and Methods: PubMed was searched using query “LG” for literature published in English from January 2000 to April 2014. A total of 875 entries were retrieved. These articles were screened and 59 manuscripts ultimately formed the basis of current review. Results: There is high-quality evidence to support short-term efficacy, safety and feasibility of LG for gastric adenocarcinomas, although accounts on long-term survivals are still infrequent.

Gastric intestinal metaplasia as detected by a monoclonal antibody is highly associated with gastric adenocarcinoma.

Science.gov (United States)

Mirza, Z K; Das, K K; Slate, J; Mapitigama, R N; Amenta, P S; Griffel, L H; Ramsundar, L; Watari, J; Yokota, K; Tanabe, H; Sato, T; Kohgo, Y; Das, K M

2003-06-01

Some forms of gastric intestinal metaplasia (GIM) may be precancerous but the cellular phenotype that predisposes to gastric carcinogenesis is not well characterised. Mucin staining, as a means of differentiating GIM, is difficult. A monoclonal antibody, mAb Das-1 (initially called 7E(12)H(12)), whose staining is phenotypically specific to colon epithelium, was used to investigate this issue. Using mAb Das-1, by a sensitive immunoperoxidase assay, we examined histologically confirmed GIM specimens from two countries, the USA and Japan. A total of 150 patients comprised three groups: group A, GIM (fields away from the cancer area) from patients with gastric carcinoma (n=60); group B, GIM with chronic gastritis (without gastric carcinoma) (n=72); and group C, chronic gastritis without GIM (n=18). Fifty six of 60 (93%) patients with GIM (both goblet and non-goblet metaplastic cells) from group A reacted intensely with mAb Das-1. Cancer areas from the same 56 patients also reacted. In contrast, 25/72 (35%) samples of GIM from patients in group B reacted with mAb Das-1 (group A v B, p<0.0001). None of the samples from group C reacted with the mAb. Reactivity of mAb Das-1 is clinically useful to simplify and differentiate the phenotypes of GIM. The colonic phenotype of GIM, as identified by mAb Das-1, is strongly associated with gastric carcinoma.

Number of Lymph Nodes Removed and Survival after Gastric Cancer Resection: An Analysis from the US Gastric Cancer Collaborative.

Science.gov (United States)

Gholami, Sepideh; Janson, Lucas; Worhunsky, David J; Tran, Thuy B; Squires, Malcolm Hart; Jin, Linda X; Spolverato, Gaya; Votanopoulos, Konstantinos I; Schmidt, Carl; Weber, Sharon M; Bloomston, Mark; Cho, Clifford S; Levine, Edward A; Fields, Ryan C; Pawlik, Timothy M; Maithel, Shishir K; Efron, Bradley; Norton, Jeffrey A; Poultsides, George A

2015-08-01

Examination of at least 16 lymph nodes (LNs) has been traditionally recommended during gastric adenocarcinoma resection to optimize staging, but the impact of this strategy on survival is uncertain. Because recent randomized trials have demonstrated a therapeutic benefit from extended lymphadenectomy, we sought to investigate the impact of the number of LNs removed on prognosis after gastric adenocarcinoma resection. We analyzed patients who underwent gastrectomy for gastric adenocarcinoma from 2000 to 2012, at 7 US academic institutions. Patients with M1 disease or R2 resections were excluded. Disease-specific survival (DSS) was calculated using the Kaplan-Meier method and compared using log-rank and Cox regression analyses. Of 742 patients, 257 (35%) had 7 to 15 LNs removed and 485 (65%) had ≥16 LNs removed. Disease-specific survival was not significantly longer after removal of ≥16 vs 7 to 15 LNs (10-year survival, 55% vs 47%, respectively; p = 0.53) for the entire cohort, but was significantly improved in the subset of patients with stage IA to IIIA (10-year survival, 74% vs 57%, respectively; p = 0.018) or N0-2 disease (72% vs 55%, respectively; p = 0.023). Similarly, for patients who were classified to more likely be "true N0-2," based on frequentist analysis incorporating both the number of positive and of total LNs removed, the hazard ratio for disease-related death (adjusted for T stage, R status, grade, receipt of neoadjuvant and adjuvant therapy, and institution) significantly decreased as the number of LNs removed increased. The number of LNs removed during gastrectomy for adenocarcinoma appears itself to have prognostic implications for long-term survival. Copyright © 2015 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

Gastric Adenocarcinoma: A Multimodal Approach

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Humair S. Quadri

2017-08-01

Full Text Available Despite its declining incidence, gastric cancer (GC remains a leading cause of cancer-related deaths worldwide. A multimodal approach to GC is critical to ensure optimal patient outcomes. Pretherapy fine resolution contrast-enhanced cross-sectional imaging, endoscopic ultrasound and staging laparoscopy play an important role in patients with newly diagnosed ostensibly operable GC to avoid unnecessary non-therapeutic laparotomies. Currently, margin negative gastrectomy and adequate lymphadenectomy performed at high volume hospitals remain the backbone of GC treatment. Importantly, adequate GC surgery should be integrated in the setting of a multimodal treatment approach. Treatment for advanced GC continues to expand with the emergence of additional lines of systemic and targeted therapies.

Anti-EGFR therapy radiosensitizes human lung adenocarcinoma xenograft in nude mouse

International Nuclear Information System (INIS)

Wang Hui; Li Tianran; Tian Jiahe; Qu Baolin; Zhu Hui

2008-01-01

Objective: To investigate the effect of Gefitinib on radiosensitivity of human lung adenocarcinoma xenograft in nude mouse. Methods: Human lung adenocarcinoma cell line A549 was used to establish nude mouse xenograft tumor model. The mice were derided into 4 groups: control, irradiation alone, Gefinitib alone and radiation combined with Genifitib. Radiation schedule was 3 fractions of 5 Gy, once daily. Gefitinib was daily administered by gavage at 100 mg/(kg·day -1 ) for 14 days. In the combination group, radiotherapy was performed 2 hours after Gefitinib administration. Tumor diameter was measured every other day. Percentage of tumor growth inhibition, growth delay time and regrowth delay time were evaluated. Results: For A549 xenografts in radiation alone, gefitinib alone and combination therapy groups, the percentage of tumor growth inhibition was 22.7%, 12.4% and 38.2%, respectively (F=25.75, P=0.000). Tumor growth delay time was 6.0, 7.8 and 21.6 days, respectively (F=70.49, P=0.000). Tumor regrowth delay time in combination therapy and irradiation alone groups was 23.4 and 10.2 days. (F=174.24, P= 0.000). Sensitizing enhancement ratio of combination group was 1.5 in growth and 1.7 in regrowth. Conclusions: Anti-EGFR therapy enhances the radiosensitivity of human lung adenocarcinoma xenograft in nude mouse. (authors)

Diagnostic significance of computed tomography in gastric cancer

International Nuclear Information System (INIS)

Kang, Eun Young; Cha, Sang Hoon; Seol, Hae Young; Chung, Kyoo Byung; Suh, Won Hyuck

1985-01-01

Gastric cancer is the most common gastrointestinal malignancy in Korea. Identification and evaluation of gastric mass lesions and regional-distant metastasis by abdominal CT scan are important for the treatment planning and prognostic implications of gastric cancer patients. Author reviewed CT scans of 61 cases of pathology proven gastric cancer, retrospectively, for recent 20 month from July 1983 to Feb. 1985 at Department of Radiology, Korea University, Hae Wha Hospital. The results were as follows: 1. There were 50 cases of advanced adenocarcinoma, 8 cases of early gastric cancer, 2 cases of leiomyosarcoma, and 1 case of lymphoma in total 61 cases. 2. The sex ratio of male to female was 2 : 1. Age distribution was from 24 to 75 year old and peak incidence was in 6th decade. 3. The most frequent site of involvement with gastric cancer was gastric antrum in 51% 4. 48 of 50 patients with advanced gastric adenocarcinoma (96%) had a wall thickness greater than 1 cm, and all of 8 cases of early gastric cancer had a wall thickness less than 1 cm. Regional lymph node tumor infiltration was found in 100% of gastric wall thickness greater than 2.0 cm, in 64% of cases of 1.5 to 2.0 cm, in 50% of cases of 1.0 to 1.5 cm, and 12.5% of cases of less than 1.0 cm. 5. In a comparison of enlargement of regional lymph node by CT scan to tumor infiltration of regional lymph node by histology, sensitivity was 52%, specificity was 87%, and reliability was 66%. 6. The structure involved by distant metastasis of these cases were the retroperitoneal lymph node in 15, liver in 8, and pancreas in 3. 7. The diagnostic accuracy of CT staging was considered about 68% by correlation of the surgical and histological findings. 8. The CT scan is one of the accurate and simple tool for evaluation of size, shape, extent, as well as distant metastasis in the cases of gastric malignancies

Apoptosis induced by GanoPoly in human gastric cancer cell line ...

African Journals Online (AJOL)

In order to investigate polysaccharide effect on the cultured human gastric cancer cells (SGC7901), DNA ladder, flow cytometry and western blot were used to examine the morpholog, proliferation and apoptosis of human gastric cancer SGC-7901 cells when they were affected by polysaccharide. Results show that ...

Selenium Status and the Risk of Esophageal and Gastric Cancer Subtypes: The Netherlands Cohort Study

NARCIS (Netherlands)

Steevens, J.; Brandt, P.A. van den; Goldbohm, R.A.; Schouten, L.J.

2010-01-01

Background & Aims: Selenium may protect against the development of esophageal squamous cell carcinoma (ESCC), esophageal adenocarcinoma (EAC), and gastric cardia adenocarcinoma (GCA). Only in very few studies have the associations with ESCC and GCA been investigated, and no epidemiologic studies

Histologic scoring of gastritis and gastric cancer in mouse models.

Science.gov (United States)

Rogers, Arlin B

2012-01-01

Histopathology is a defining endpoint in mouse models of experimental gastritis and gastric adenocarcinoma. Presented here is an overview of the histology of gastritis and gastric cancer in mice experimentally infected with Helicobacter pylori or H. felis. A modular histopathologic scoring scheme is provided that incorporates relevant disease-associated changes. Whereas the guide uses Helicobacter infection as the prototype challenge, features may be applied to chemical and genetically engineered mouse models of stomach cancer as well. Specific criteria included in the combined gastric histologic activity index (HAI) include inflammation, epithelial defects, oxyntic atrophy, hyperplasia, pseudopyloric metaplasia, and dysplasia or neoplasia. Representative photomicrographs accompany descriptions for each lesion grade. Differentiation of genuine tumor invasion from pseudoinvasion is highlighted. A brief comparison of normal rodent versus human stomach anatomy and physiology is accompanied by an introduction to mouse-specific lesions including mucous metaplasia and eosinophilic droplets (hyalinosis). In conjunction with qualified pathology support, this guide is intended to assist research scientists, postdoctoral fellows, graduate students, and medical professionals from affiliated disciplines in the interpretation and histologic grading of chronic gastritis and gastric carcinoma in mouse models.

Regulation of apoptosis is impaired in atrophic gastritis associated with gastric cancer.

Science.gov (United States)

Rosania, R; Varbanova, M; Wex, T; Langner, C; Bornschein, J; Giorgio, F; Ierardi, E; Malfertheiner, P

2017-06-29

Gastric premalignant conditions, atrophic gastritis (AG) and intestinal metaplasia (IM) are characterized by an increase of proliferation and a reduction of apoptosis in epithelial cells. The epithelial cell kinetics in AG and IM in gastric mucosa adjacent to gastric cancer is still unclear. The aim of this study was to evaluate the epithelial cell turnover and expression of proliferation and apoptosis-related genes in gastric cancer (GC) and adjacent mucosa with atrophic gastritis or intestinal metaplasia (AG/IM GC+), as well as in atrophic gastritis or intestinal metaplasia mucosa of patients without GC (AG/IM GC-) and in control biopsy samples of non-transformed gastric mucosa (Control). We selected 58 patients (M: F = 34:24; age range 20-84 years, median 61.06 years) with 4 well defined histological conditions: 20 controls with histological finding of non-transformed gastric mucosa, 20 patients with AG or IM (AG/IM GC-), and 18 patients with intestinal type gastric adenocarcinoma (GC) and AG or IM in the adjacent mucosa (3 cm from the macroscopic tumour margin, AG/IM GC+). We performed an immunohistochemical staining of Ki67 and TUNEL and quantitative RT-PCR to determine the expression of PCNA and Bax/Bcl-2. The immunohistochemical expression of Ki67 and TUNEL in AG/IM GC- was significantly increased compared to not transformed gastric mucosa (p gastritis and IM in presence of cancer, as well as intestinal type gastric adenocarcinoma.

Immuno-Oncology Biomarkers for Gastric and Gastroesophageal Junction Adenocarcinoma: Why PD-L1 Testing May Not Be Enough.

Science.gov (United States)

Weinberg, Benjamin A; Xiu, Joanne; Hwang, Jimmy J; Shields, Anthony F; Salem, Mohamed E; Marshall, John L

2018-04-27

The treatment of patients with advanced gastric and gastroesophageal junction (G/GEJ) adenocarcinomas has been transformed by the U.S. Food and Drug Administration approval of pembrolizumab. Tumor and adjacent tissue must stain positively for the programmed cell death ligand 1 (PD-L1) protein by companion diagnostic testing. However, some patients with PD-L1-negative tumors also benefit from pembrolizumab. High microsatellite instability (MSI) and tumor mutational load (TML) are positive predictive biomarkers for immune checkpoint inhibition (ICI) in other tumors. We sought to identify more patients who could benefit from ICI using alternative PD-L1 thresholds, MSI, and TML. Tumor specimens underwent next-generation sequencing (NGS) and PD-L1 testing using immunohistochemistry. NGS was used to determine TML and MSI. We profiled 581 G/GEJ adenocarcinoma specimens. PD-L1 staining was scored for intensity (0, none; 1+, weak; 2+, moderate; 3+, strong). Using 2+ staining at a 5% threshold, 9.3% of tumors were PD-L1 positive, and using 1+ staining at 1%, 16.2% were PD-L1 positive. 6.9% of tumors had high MSI. High TML (≥17 mutations per megabase) was seen in 6.9%, and medium TML (≥7) was seen in 56.5% of tumors. Thirty (5.2%) PD-L1-negative tumors at the 1+, 1% threshold had high TML or high MSI. Primary tumors had higher rates of high TML (8.8% vs. 3.9%; p  = .0377) and high MSI (8.5% vs. 3.9%; p  = .0471) than metastases. PD-L1 testing alone fails to detect patients who may benefit from ICI. Lower PD-L1 thresholds and TML testing should be considered in future clinical trials. Pembrolizumab is approved by the U.S. Food and Drug Administration for patients with refractory gastric and gastroesophageal cancers if the tumor and adjacent tissue stain positively for the programmed cell death ligand 1 (PD-L1) protein by companion diagnostic testing. Tumor mutational load, microsatellite instability (MSI), and alternative PD-L1 testing thresholds may serve as

Results of adjuvant chemo radiation after curative surgery for gastric cancer. A retrospective study

International Nuclear Information System (INIS)

Muller, Bettina; Balbontin, Paulina; Trujillo, Cristian; Becerra, Sergio; Sola, Antonio; Neveu, Rodrigo; Fernandez, Roberto; Buchholtz, Martin; Villanueva, Luis; Cerda, Berta

2009-01-01

Background: Survival rates after curative surgery for gastric cancer are disappointing. Therefore adjuvant therapeutic strategies are required. Aim: To analyze survival and side effects of treatment among gastric cancer patients treated with adjuvant chemoradiotherapy after curative resection of gastric adenocarcinoma. Material and methods: Retrospective review of medical records of 74 patients aged 20 to 74 years, treated with complete resection of gastric adenocarcinoma followed by adjuvant chemo radiation. Survival analysis was based on the records and information from the National Mortality Registry. Results: Five years survival fluctuated from 50% among patients in stage 1B to 25% among those is stage IV. Significant acute toxicity was observed in 23 patients (31%). No patients died due to acute toxicity. Eleven patients (16.4%) developed significant late toxicity, with two possible deaths related to treatment. Conclusions: Postoperative chemoradiotherapy is feasible in our experience. Continuos infusion of 5- fluoruracil is recommended to reduce toxicity

Contribution of H. pylori and smoking trends to US incidence of intestinal-type noncardia gastric adenocarcinoma: a microsimulation model.

Directory of Open Access Journals (Sweden)

Jennifer M Yeh

Full Text Available Although gastric cancer has declined dramatically in the US, the disease remains the second leading cause of cancer mortality worldwide. A better understanding of reasons for the decline can provide important insights into effective preventive strategies. We sought to estimate the contribution of risk factor trends on past and future intestinal-type noncardia gastric adenocarcinoma (NCGA incidence.We developed a population-based microsimulation model of intestinal-type NCGA and calibrated it to US epidemiologic data on precancerous lesions and cancer. The model explicitly incorporated the impact of Helicobacter pylori and smoking on disease natural history, for which birth cohort-specific trends were derived from the National Health and Nutrition Examination Survey (NHANES and National Health Interview Survey (NHIS. Between 1978 and 2008, the model estimated that intestinal-type NCGA incidence declined 60% from 11.0 to 4.4 per 100,000 men, <3% discrepancy from national statistics. H. pylori and smoking trends combined accounted for 47% (range = 30%-58% of the observed decline. With no tobacco control, incidence would have declined only 56%, suggesting that lower smoking initiation and higher cessation rates observed after the 1960s accelerated the relative decline in cancer incidence by 7% (range = 0%-21%. With continued risk factor trends, incidence is projected to decline an additional 47% between 2008 and 2040, the majority of which will be attributable to H. pylori and smoking (81%; range = 61%-100%. Limitations include assuming all other risk factors influenced gastric carcinogenesis as one factor and restricting the analysis to men.Trends in modifiable risk factors explain a significant proportion of the decline of intestinal-type NCGA incidence in the US, and are projected to continue. Although past tobacco control efforts have hastened the decline, full benefits will take decades to be realized, and further discouragement of smoking and

The newly proposed clinical and post-neoadjuvant treatment staging classifications for gastric adenocarcinoma for the American Joint Committee on Cancer (AJCC) staging.

Science.gov (United States)

In, Haejin; Ravetch, Ethan; Langdon-Embry, Marisa; Palis, Bryan; Ajani, Jaffer A; Hofstetter, Wayne L; Kelsen, David P; Sano, Takeshi

2018-01-01

New stage grouping classifications for clinical (cStage) and post-neoadjuvant treatment (ypStage) stage for gastric adenocarcinoma have been proposed for the eighth edition of the AJCC manual. This article summarizes the analysis for these stages. Gastric adenocarcinoma patients diagnosed in 2004-2009 were identified from the National Cancer Database (NCDB). The cStage cohort included both surgical and nonsurgical cases, and the ypStage cohort included only patients who had chemotherapy or radiation therapy before surgery. Survival differences between the stage groups were determined by the log-rank test and prognostic accuracy was assessed by concordance index. Analysis was performed using SAS 9.4 (SAS, Cary, NC, USA). Five strata for cStage and four strata for ypStage were developed. The 5-year survival rates for cStages were 56.77%, 47.39%, 33.1%, 25.9%, and 5.0% for stages I, IIa, IIb, III, and IV, respectively, and the rates for ypStage were 74.2%, 46.3%, 19.2%, and 11.6% for stages I, II, III, and IV, respectively. The log-rank test showed that survival differences were well stratified and stage groupings were ordered and distinct (p < 0.0001). The proposed cStage and ypStage classification was sensitive and specific and had high prognostic accuracy (cStage: c index = 0.81, 95% CI, 0.79-0.83; ypStage: c index = 0.80, 95% CI, 0.73-0.87). The proposed eighth edition establishes two new staging schemata that provide essential prognostic data for patients before treatment and for patients who have undergone surgery following neoadjuvant therapy. These additions are a significant advance to the AJCC staging manual and will provide critical guidance to clinicians in making informed decisions throughout the treatment course.

Metastasis of Gastric Signet-Ring Cell Carcinoma to the Urinary Bladder: A Case Report and Review of the Literature

Directory of Open Access Journals (Sweden)

Kerem Okutur

2015-01-01

Full Text Available Although signet-ring cell (SRC adenocarcinoma is commonly seen in the stomach, it is a very rarely seen histologic entity in the bladder. It is difficult to distinguish primary SRC adenocarcinoma of the bladder from bladder metastasis of SRC carcinoma of the stomach only based on histological findings. In such cases, clinical findings and immunohistochemical studies may be helpful. We present here a 48-year-old male patient presenting with hematuria and abdominal pain. Computerised tomography of the patient revealed a gastric mass, peritoneal involvement, and thickening of the bladder wall, and histopathological analysis revealed SRC adenocarcinoma in both of the endoscopic biopsies taken from the stomach and bladder. Immunohistochemical analyses confirmed the diagnosis of SRC adenocarcinoma of the bladder secondary to gastric cancer.

[Current standards in the treatment of gastric cancer].

Science.gov (United States)

Hacker, Ulrich; Lordick, Florian

2015-08-01

Endoscopic resection is established in the treatment of early gastric cancer. More advanced gastric cancer requires gastrectomy and D2 lymphadenectomy. Perioperative chemotherapy improves overall survival in locally advanced gastric cancer representing a standard of care. Locally advanced adenocarcinomas of the esophago-gastric junction can alternatively be treated with concurrent radiochemotherapy. In metastatic disease, systemic chemotherapy improves survival, quality of life and symptom control. Trastuzumab plus chemotherapy should be used together with first-line chemotherapy in HER2 positive gastric cancer patients. Second- and third-line therapy is now well established. The anti-VEGFR2 antibody Ramucirumab improves survival in second line treatment both as a monotherapy and in combination with paclitaxel and represents a novel treatment option. © Georg Thieme Verlag KG Stuttgart · New York.

Squamous metaplasia induced by transfection of human papillomavirus DNA into cultured adenocarcinoma cells

OpenAIRE

Kinjo, T; Kamiyama, K; Chinen, K; Iwamasa, T; Kurihara, K; Hamada, T

2003-01-01

Background/Aim: It has been reported previously in cases of adenosquamous carcinoma of the lung in Okinawa, a subtropical island 2000 km south of mainland Japan, that the squamous cell carcinoma components were positive for human papillomavirus (HPV) by non-isotopic in situ hybridisation (NISH). The adenocarcinoma cells adjacent to the squamous cell carcinoma components were enlarged and also positive for HPV. This is thought to indicate that after adenocarcinoma cells are infected with HPV, ...

Surveillance of gastric intestinal metaplasia for the prevention of gastric cancer.

LENUS (Irish Health Repository)

O'Connor, Anthony

2013-01-01

Adenocarcinoma of the stomach is the second leading cause of cancer related death in the world. Gastric intestinal metaplasia (GIM) is a recognised premalignant condition of the stomach. It has been described as occurring in up to one in five patients in western countries. Although there is a definite risk of progression from GIM to cancer, published guidelines and statements differ as to the utility and structure of surveillance programs for this condition.

Up-regulation of CLDN1 in gastric cancer is correlated with reduced survival

International Nuclear Information System (INIS)

Eftang, Lars L; Esbensen, Ying; Tannæs, Tone M; Blom, Gustav P; Bukholm, Ida RK; Bukholm, Geir

2013-01-01

The genetic changes in gastric adenocarcinoma are extremely complex and reliable tumor markers have not yet been identified. There are also remarkable geographical differences in the distribution of this disease. Our aim was to identify the most differentially regulated genes in 20 gastric adenocarcinomas from a Norwegian selection, compared to matched normal mucosa, and we have related our findings to prognosis, survival and chronic Helicobacter pylori infection. Biopsies from gastric adenocarcinomas and adjacent normal gastric mucosa were obtained from 20 patients immediately following surgical resection of the tumor. Whole genome, cDNA microarray analysis was performed on the RNA isolated from the sample pairs to compare the gene expression profiles between the tumor against matched mucosa. The samples were microscopically examined to classify gastritis. The presence of H. pylori was examined using microscopy and immunohistochemistry. 130 genes showed differential regulation above a predefined cut-off level. Interleukin-8 (IL-8) and Claudin-1 (CLDN1) were the most consistently up-regulated genes in the tumors. Very high CLDN1 expression in the tumor was identified as an independent and significant predictor gene of reduced post-operative survival. There were distinctly different expression profiles between the tumor group and the control mucosa group, and the histological subsets of mixed type, diffuse type and intestinal type cancer demonstrated further sub-clustering. Up-regulated genes were mapped to cell-adhesion, collagen-related processes and angiogenesis, whereas normal intestinal functions such as digestion and excretion were associated with down-regulated genes. We relate the current findings to our previous study on the gene response of gastric epithelial cells to H. pylori infection. CLDN1 was highly up-regulated in gastric cancer, and CLDN1 expression was independently associated with a poor post-operative prognosis, and may have important prognostic

Effect of sialoadenectomy and synthetic human urogastrone on healing of chronic gastric ulcers in rats

DEFF Research Database (Denmark)

Poulsen, Steen Seier; Nexø, Ebba

1986-01-01

The effect of extirpation of the submandibular glands, an exocrine organ for epidermal growth factor/urogastrone (EGF/URO), and the effect of oral administration of synthetic human (EGF/URO) on healing of chronic gastric ulcers in rats has been investigated. Removal of the submandibular glands...... delayed healing of chronic gastric ulcers when examined after 50, 100, and 200 days. Oral administration of synthetic human EGF/URO stimulated gastric ulcer healing when examined after 25 and 50 days of treatment. The effect of synthetic human EGF/URO was comparable with that of cimetidine. The combined...... administration of synthetic human EGF/URO and cimetidine further increased healing of gastric ulcers compared with administration of each substance. Neither synthetic human EGF/URO, nor removal of the submandibular glands had any influence on gastric acid secretion. This study showed that the submandibular...

Calcifying mucinous adenocarcinoma of the stomach: Report of two cases

International Nuclear Information System (INIS)

Sung, Ki Yeal; Han, Seong Tai; Bahk, Yong Whee

1983-01-01

There is a great variety of abdominal calcifications of varying etiology. Among them, calcification in gastric carcinoma is rare. To the best of our knowledge, there has been no previous report of calcifying mucinous adenocarcinoma of the stomach in Korea. In the present communication, we report toe cases of this rare tumor. The first cases was 27 years old female who had anorexia and palpable mass in the epigastrium. By palpation, a firm non-tender large mass was felt in the epigastrium. A plain abdominal film showed numerous punctuate calcifications in the left upper quadrant. Film from an upper G-I series demonstrated findings of advanced gastric carcinoma with multiple punctuate calcifications involving the antrum and body. Gastroscopic biopsy proved the lesion to be mucinous adenocarcinoma (signet ring cell type). The second case was 38 years old female who complicated of nausea, vomiting and weight loss. On physical examination, she appeared normal. Routine laboratory tests were within normal limits. A plain abdominal film reveal stippled calcifications in the left upper quadrant medial to the splenic shadow. The film from an upper G-I series showed a mass in the fundus and upper body of stomach with multiple stippled calcifications along the lesser curvature. Subtotal gastrectomy was performed and the pathologic finding was calcifying mucinous adenocarcinoma (signet ring cell type)

Osteogenesis Imperfecta, Pseudoachalasia, and Gastric Cancer

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Dilsa Mizrak

2015-01-01

Full Text Available Osteogenesis imperfecta (OI is a rare, inherited skeletal disorder characterized by abnormalities of type 1 collagen. Malignancy is rarely reported in patients with OI and it was suggested that this disease can protect against cancer. Here, we report a 41-year-old woman with symptoms of achalasia where repeated treatment of pneumatic dilation and stent replacement was unsuccessful; therefore, surgery was performed. Pathology showed gastric adenocarcinoma unexpectedly. Chemotherapy was given after assessing dihydropyrimidine dehydrogenase (DPD enzyme activity, which can be deficient in OI patients. This is the first report of gastric cancer mimicking achalasia in a patient with OI.

Honey and Apoptosis in Human Gastric Mucosa

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Alireza Ostadrahimi

2012-07-01

Full Text Available Background: Gastric cancer is the fourth most common malignancy in the world. Honey is acomplex mixture of special biological active constituents. Honey possesses antioxidant and antitumorproperties. Nutritional studies have indicated that consumption of honey modulates therisk of developing gastric cancer. On the other hand, apoptosis has been reported to play a decisiverole in precancerous changes. Our chief study was conducted to assess the relationship betweenconsumption of honey and apoptosis in human gastric mucosa.Method: This cross-sectional study was conducted on 98 subjects over 18 years old, referred totwo hospitals in Tabriz, Iran. Subjects were undergone an upper gastrointestinal endoscopy, 62subjects were finally enrolled. Honey consumption was assessed by a Food Frequency Questionnaire(FFQ and apoptosis was detected by TUNEL technique. We tested polynomial curve tofind the best fit between honey consumption and apoptosis.Results: A positive relation between honey consumption and apoptosis was found (P=0.024.Our results indicated that the final and the best fit curve was: apoptosis = 1.714+1.648(honeyamount - 0.533(honey amount2 +1.833×10-5(honey amount7.Conclusion: Honey consumption had positive effects on gastric cancer by inducing apoptosis ingastric mucosa.

Vegetables and fruits consumption and risk of esophageal and gastric cancer subtypes in the Netherlands Cohort Study

NARCIS (Netherlands)

Steevens, J.; Schouten, L.J.; Goldbohm, R.A.; Brandt, P.A. van den

2011-01-01

Prospective epidemiologic data on vegetables and fruits consumption and risk of subtypes of esophageal and gastric cancer are sparse. We studied the association between vegetables and fruits consumption and risk of esophageal squamous cell carcinoma (ESCC), esophageal adenocarcinoma (EAC), gastric

Adenocarcinoma of the pouch after silastic ring vertical gastroplasty.

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Zirak, Christophe; Lemaitre, Jean; Lebrun, Eric; Journé, Stephane; Carlier, Patrick

2002-10-01

A 52-year-old woman was admitted because of epigastralgia, anorexia and recently increased vomiting, 2 years after silastic ring vertical gastroplasty. On gastroscopy, a tumor mass was visualized in the pouch near the "neo-pylorus". Biopsies confirmed adenocarcinoma. She underwent total gastrectomy, and has no evidence of recurrence at 1 year. The literature on gastric carcinoma after gastroplasty is reviewed.

Heterotopic Gastric Mucosa in the Distal Part of Esophagus in a Teenager: Case Report.

Science.gov (United States)

Lupu, Vasile Valeriu; Ignat, Ancuta; Paduraru, Gabriela; Mihaila, Doina; Burlea, Marin; Ciubara, Anamaria

2015-10-01

Heterotopic gastric mucosa (HGM) of the esophagus is a congenital anomaly consisting of ectopic gastric mucosa. It may be connected with disorders of the upper gastrointestinal tract, exacerbated by Helicobacter pylori. The diagnosis of HGM is confirmed via endoscopy with biopsy. Histopathology provides the definitive diagnosis by demonstrating gastric mucosa adjacent to normal esophageal mucosa. HGM located in the distal esophagus needs differentiation from Barrett's esophagus. Barrett's esophagus is a well-known premalignant injury for adenocarcinoma of the esophagus. Malignant progression of HGM occurs in a stepwise pattern, following the metaplasia-dysplasia-adenocarcinoma sequence.We present a rare case of a teenage girl with HGM located in the distal esophagus, associated with chronic gastritis and biliary duodenogastric reflux. Endoscopy combined with biopsies is a mandatory method in clinical evaluation of metaplastic and nonmetaplastic changes within HGM of the esophagus.

High expression of atypical protein kinase C lambda/iota in gastric cancer as a prognostic factor for recurrence.

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Takagawa, Ryo; Akimoto, Kazunori; Ichikawa, Yasushi; Akiyama, Hirotoshi; Kojima, Yasuyuki; Ishiguro, Hitoshi; Inayama, Yoshiaki; Aoki, Ichiro; Kunisaki, Chikara; Endo, Itaru; Nagashima, Yoji; Ohno, Shigeo

2010-01-01

The atypical protein kinase C lambda/iota (aPKClambda/iota) is involved in several signal transduction pathways that influence cell growth, apoptosis, and the establishment and maintenance of epithelial cell polarity. Overexpression of aPKClambda/iota has been reported in several cancers and been shown to be associated with oncogenesis. However, the expression and role of aPKClambda/iota in gastric cancer, one of the commonest cancers in Asia, have not so far been investigated. This study aimed to clarify the relationship between aPKClambda/iota expression and the clinicopathological features of gastric cancer. Gastric adenocarcinoma samples were obtained from 177 patients who underwent gastrectomy at the Yokohama City University Hospital between 1999 and 2004. Expression of aPKClambda/iota and E: -cadherin was examined immunohistochemically and compared with clinicopathological features of the tumors. Univariate and multivariate analyses were performed for both disease-specific and relapse-free survival. Overexpression of aPKClambda/iota protein was detected in 126 of the 177 (71.2%) gastric cancers. Immunohistological staining for aPKClambda/iota was stronger in gastric adenocarcinoma of intestinal type than diffuse type (p = 0.036), but was not correlated with E: -cadherin expression. A multivariate analysis suggested that nodal metastasis and aPKClambda/iota overexpression were prognostic factors for disease recurrence. Our results suggested that aPKClambda/iota overexpression was a strong prognostic factor for gastric adenocarcinoma recurrence. As well as being a new prognostic indicator, aPKClambda/iota is also likely to be a novel therapeutic target for gastric cancer.

Magnetogastrographic detection of gastric electrical response activity in humans

International Nuclear Information System (INIS)

Irimia, Andrei; Richards, William O; Bradshaw, L Alan

2006-01-01

The detection and characterization of gastric electrical activity has important clinical applications, including the early diagnosis of gastric diseases in humans. In mammals, this phenomenon has two important features: an electrical control activity (ECA) that manifests itself as an electric slow wave (with a frequency of 3 cycles per minute in humans) and an electrical response activity (ERA) that is characterized by spiking potentials during the plateau phase of the ECA. Whereas the ECA has been recorded in humans both invasively and non-invasively (magnetogastrography-MGG), the ERA has never been detected non-invasively in humans before. In this paper, we report on our progress towards the non-invasive detection of ERA from the human stomach using a procedure that involves the application of principal component analysis to MGG recordings, which were acquired in our case from ten normal human patients using a Superconducting QUantum Interference Device (SQUID) magnetometer. Both pre- and post-prandial recordings were acquired for each patient and 20 min of recordings (10 min of pre-prandial and 10 min of post-prandial data) were analysed for each patient. The mean percentage of ECA slow waves that were found to exhibit spikes of suspected ERA origin was 41% and 61% for pre- and post-prandial recordings, respectively, implying a 47% ERA increase post-prandially (P < 0.0001 at a 95% confidence level). The detection of ERA in humans is highly encouraging and points to the possible use of non-invasive ERA recordings as a valuable tool for the study of human gastric disorders

Gastric metastasis from invasive lobular breast cancer, mimicking primary gastric cancer: A case report.

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Kim, Dae Hoon; Son, Seung-Myoung; Choi, Young Jin

2018-03-01

Gastric metastasis from invasive lobular breast cancer is relatively rare, commonly presented among multiple metastases, several years after primary diagnosis of breast cancer. Importantly, gastric cancer that is synchronously presented with lobular breast cancer can be misdiagnosed as primary gastric cancer; therefore, accurate differential diagnosis is required. A 39-year-old woman was visited to our hospital because of right breast mass and progressive dyspepsia. Invasive lobular carcinoma of breast was diagnosed on core needle biopsy. Gastroscopy revealed a diffuse scirrhous mass at the prepyloric antrum and diagnosed as poorly differentiated adenocarcinoma on biopsy. Synchronous double primary breast and gastric cancers were considered. Detailed pathological analysis focused on immunohistochemical studies of selected antibodies, including those of estrogen receptors, gross cystic disease fluid protein-15, and caudal-type homeobox transcription factor 2, were studied. As a result, gastric lesion was diagnosed as metastatic gastric cancer originating from breast. Right breast conserving surgery was performed, and duodenal stent was inserted under endoscopic guidance to relieve the patient's symptoms. Systemic chemotherapy with combined administration of paclitaxel and trastuzumab was initiated. Forty-one months after the diagnosis, the patient is still undergoing the same therapy. No recurrent lesion has been identified in the breast and evidence of a partial remission of gastric wall thickening has been observed on follow-up studies without new metastatic lesions. Clinical suspicion, repeat endoscopic biopsy, and detailed histological analysis, including immunohistochemistry, are necessary for diagnosis of metastatic gastric cancer from the breast.

Curative resection by splenectomy for solitary splenic metastasis from early gastric cancer: a case report and literature review.

Science.gov (United States)

Yoshizawa, Junichi; Kubo, Naoki; Ishizone, Satoshi; Karasawa, Fumitoshi; Nakayama, Ataru

2017-06-20

Solitary metastasis of a malignancy to the spleen is rare, particularly for gastric cancer. Only a few case reports have documented isolated splenic metastasis from early gastric cancer. We describe a case of splenic metastasis from early gastric cancer. A 60-year-old man underwent a distal gastrectomy for early gastric cancer. It infiltrated the submucosa with pathological nodal involvement (pT1bN2M0, stage IIB). One year after the gastrectomy, an abdominal computed tomography scan showed a low-density lesion, 17 mm in diameter, at the upper pole of the spleen. Positron emission tomography/computed tomography showed focal accumulation of fluorine-18 fluorodeoxyglucose in the spleen without extrasplenic tumor dissemination or metastasis. We diagnosed splenic metastasis of gastric cancer, and performed a splenectomy. Histological examination confirmed moderately differentiated tubular adenocarcinoma and poorly differentiated adenocarcinoma (solid type) that was consistent with the features of the primary gastric cancer. The splenic tumor was pathologically and immunohistochemically diagnosed as a metastasis from the gastric carcinoma. More than 18 months after the splenectomy, the patient has had no evidence of recurrent gastric cancer. When solitary metastasis to the spleen is suspected during the postoperative follow-up of a patient with gastric cancer, a splenectomy is a potentially effective treatment.

The Prevalence of Gastric Intestinal Metaplasia and Distribution of Helicobacter pylori Infection, Atrophy, Dysplasia, and Cancer in Its Subtypes.

Science.gov (United States)

Olmez, Sehmus; Aslan, Mehmet; Erten, Remzi; Sayar, Suleyman; Bayram, Irfan

2015-01-01

Objectives. Gastric intestinal metaplasia (IM) is frequently encountered and is considered a precursor of gastric adenocarcinoma. In the Van region of Turkey, gastric adenocarcinoma incidence is high but the prevalence of gastric IM is not known. Helicobacter pylori (H. pylori) infection is a main factor leading to atrophy, IM, and cancer development in the stomach. The aim of the current study was to investigate the prevalence of IM and its subtypes and the prevalence of H. pylori infection, atrophy, dysplasia, and cancer in gastric IM subtypes. Materials and Methods. This retrospective study was conducted on 560 IM among the 4050 consecutive patients who were undergoing esophagogastroduodenoscopy (EGD) with biopsy between June 2010 and October 2014. Clinical records and endoscopic and histopathologic reports of patients with IM were analyzed. Results. The prevalence of gastric IM was 13.8%. The prevalence of incomplete IM was statistically significantly higher than complete IM. Type III IM was the most frequent subtype. Conclusions. Gastric IM is a common finding in patients undergoing EGD with biopsy in this region. High prevalence of incomplete type IM, especially type III, can be associated with the high prevalence of gastric cancer in our region.

The Prevalence of Gastric Intestinal Metaplasia and Distribution of Helicobacter pylori Infection, Atrophy, Dysplasia, and Cancer in Its Subtypes

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Sehmus Olmez

2015-01-01

Full Text Available Objectives. Gastric intestinal metaplasia (IM is frequently encountered and is considered a precursor of gastric adenocarcinoma. In the Van region of Turkey, gastric adenocarcinoma incidence is high but the prevalence of gastric IM is not known. Helicobacter pylori (H. pylori infection is a main factor leading to atrophy, IM, and cancer development in the stomach. The aim of the current study was to investigate the prevalence of IM and its subtypes and the prevalence of H. pylori infection, atrophy, dysplasia, and cancer in gastric IM subtypes. Materials and Methods. This retrospective study was conducted on 560 IM among the 4050 consecutive patients who were undergoing esophagogastroduodenoscopy (EGD with biopsy between June 2010 and October 2014. Clinical records and endoscopic and histopathologic reports of patients with IM were analyzed. Results. The prevalence of gastric IM was 13.8%. The prevalence of incomplete IM was statistically significantly higher than complete IM. Type III IM was the most frequent subtype. Conclusions. Gastric IM is a common finding in patients undergoing EGD with biopsy in this region. High prevalence of incomplete type IM, especially type III, can be associated with the high prevalence of gastric cancer in our region.

Advances in the diagnosis and treatment of gastric neuroendocrine neoplasms

OpenAIRE

Tan, Huangying

2016-01-01

Gastric neuroendocrine neoplasms (g-NENs) are a group of heterogeneous tumors arising from the endocrine cells of stomach. Most g-NENs progresses slowly and have a long disease course; however, some other g-NENs grow rapidly, similar to the progression of gastric adenocarcinoma. g-NENs have complex and diverse clinical manifestations and their prognosis and treatment strategies depend highly on clinical subtype, pathological grade, tumour stage, and other factors. Due to their low prevalence,...

[Gastric cancer: epidemiologic profile 2001-2007 in Lima, Peru].

Science.gov (United States)

Chirinos, Jesús L; Carbajal, Luz A; Segura, María D; Combe, J; Akiba, S

2012-01-01

To describe and compare the demographic and social characteristics as well as lifestyles of patients with gastric cancer against patients with other important gastric disorders, who attended at main reference health services in Lima, Peru. Case control study, matched by sex and age + 2 years, applying a questionnaire to 96 cases with gastric cancer, and to 96 controls from September 2001 to November 2007. There were no significant differences about ethnicity; marital status; exposure to minerals, wood, and metal dusts; tobacco and alcohol; red meat consumption; salt addition; food temperature. 87, 5% of the control group had lesions in the gastric antrum, and 73% of cases group had a tubular adenocarcinoma (56%) in the gastric antrum. There was no family history of cancer in 85% patients of cases group and 59% of controls, (with significant difference). There were significant differences in low scholarship level of cases, as well as for their mothers and fathers (OR 3.75, 3.9, and 3.49 respectively), fruit or vegetables intake, milk or cheese consumption (minus of once a day) (OR 2, 3, 2, 57 and 2, 9 respectively), type of fuel for cooking (firewood, charcoal, and kerosene OR 5, 25), lack of use of refrigerator (OR 8, 4). The profile of a gastric cancer patient was to proceed from the Andean zone (high altitude +3000 meters over sea level) and jungle, low education level (low socioeconomic level), low consumption of fruits, vegetables and milk, use of firewood, charcoal, or kerosene to cook, and no use of refrigerator. The most frequent histological diagnosis in the case group was tubular adenocarcinoma.

Gastric cancer metastasis mimicking primary lung cancer - case report and review of the literature; Metastase de cancer gastrico simulando neoplasia primaria de pulmao - relato de caso e revisao da literatura

Energy Technology Data Exchange (ETDEWEB)

Escuissato, Dante Luiz; Ledesma, Jorge Alberto; Urban, Linei Augusta Brolini Delle; Liu, Cristhian Bau [Parana Univ., Curitiba, PR (Brazil). Hospital de Clinicas. Servico de Radiologia]. E-mail: info@dapi.com.br; Reis Filho, Jorge Sergio [Parana Univ., Curitiba, PR (Brazil). Hospital de Clinicas. Servico de Patologia; Oliveira Filho, Adilson Gil; Ferri, Mauricio Beller; Hossaka, Marco Aurelio [Parana Univ., Curitiba, PR (Brazil). Hospital de Clinicas

2002-04-01

Gastric cancer frequently presents intraperitoneal spread. Distant metastasis are rare. The authors describe a case of a 47-year-old white man, long-term cigarette smoker, who had a right upper lobe mass seen on plain films and computed tomography of the chest. A gastric adenocarcinoma was concomitantly diagnosed by endoscopic examination. A bronchoscopy guided biopsy showed that the lung mass was in fact a metastasis from gastric adenocarcinoma. In this article, the imaging findings of gastric cancer and the patterns of dissemination to other organs are reviewed. (author)

Is It Barrett's Esophagus or Gastric Heterotopia

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Zeynel Mungan

2014-10-01

Full Text Available Columnar epithelium in the distal part of the esophagus is generally related to Barrett's esophagus. Barrett's esophagus is a well-known premalignant lesion for adenocarcinoma of the esophagus. Therefore, its diagnosis and surveillance are important. Columnar epithelium in the esophagus other than Barrett's esophagus can be gastric heterotopia, which generally takes place in the upper part of the esophagus and is named inlet patch. The presence of gastric metaplasia in the distal part of the esophagus is rare and can cause misdiagnosis. Therefore, its differentiation from Barrett's esophagus is important. Here we present a case of gastric heterotopia located in the distal part of the esophagus that caused reflux-like symptoms and needed differentiation from Barrett's esophagus.

A naturally derived gastric cancer cell line shows latency I Epstein-Barr virus infection closely resembling EBV-associated gastric cancer

International Nuclear Information System (INIS)

Oh, Sang Taek; Seo, Jung Seon; Moon, Uk Yeol; Kang, Kyeong Hee; Shin, Dong-Jik; Yoon, Sungjoo Kim; Kim, Woo Ho; Park, Jae-Gahb; Lee, Suk Kyeong

2004-01-01

In a process seeking out a good model cell line for Epstein-Barr virus (EBV)-associated gastric cancer, we found that one previously established gastric adenocarcinoma cell line is infected with type 1 EBV. This SNU-719 cell line from a Korean patient expressed cytokeratin without CD19 or CD21 expression. In SNU-719, EBNA1 and LMP2A were expressed, while LMP1 and EBNA2 were not. None of the tested lytic EBV proteins were detected in this cell line unless stimulated with phorbol ester. EBV infection was also shown in the original carcinoma tissue of SNU-719 cell line. Our results support the possibility of a CD21-independent EBV infection of gastric epithelial cells in vivo. As the latent EBV gene expression pattern of SNU-719 closely resembles that of the EBV-associated gastric cancer, this naturally derived cell line may serve as a valuable model system to clarify the precise role of EBV in gastric carcinogenesis

Effect of Native Gastric Mucus on in vivo Hybridization Therapies Directed at Helicobacter pylori

DEFF Research Database (Denmark)

Santos, Rita S; Dakwar, George R; Xiong, Ranhua

2015-01-01

Helicobacter pylori infects more than 50% of the worldwide population. It is mostly found deep in the gastric mucus lining of the stomach, being a major cause of peptic ulcers and gastric adenocarcinoma. To face the increasing resistance of H. pylori to antibiotics, antimicrobial nucleic acid...... barriers-the highly viscoelastic gastric mucus and the bacterial cell envelope. We found that LNA/2'OMe is capable of diffusing rapidly through native, undiluted, gastric mucus isolated from porcine stomachs, without degradation. Moreover, although LNA/2'OMe hybridization was still successful without...

Cancer of the esophagus and gastric cardia: recent advances

NARCIS (Netherlands)

Tytgat, G. N. J.; Bartelink, H.; Bernards, R.; Giaccone, G.; van Lanschot, J. J. B.; Offerhaus, G. J. A.; Peters, G. J.

2004-01-01

Esophageal cancer and cancer of the gastric cardia, in particular adenocarcinomas, have shown a rapid and largely unexplained increase in incidence in many developed countries around the world. These diseases have a poor prognosis and current therapies have a modest impact on survival. This review

Bone metastases from gastric cancer. Clinical evaluation on bone scintigram

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Seto, Mikito; Tonami, Norihisa; Koizumi, Kiyoshi; Sui, Osamu; Hisada, Kinichi [Kanazawa Univ. (Japan). School of Medicine

1983-07-01

We have studied bone scintigrams in 60 patients with gastric cancer. Of these 60 patients, bone metastases were found in 15 patients (25 %). There were no evidence of bone metastases in polypoid lesions, cancers of the antrum, carcinomas in situ, advanced cancers without invasion to serosa, cancer with N/sub 0/ or N/sub 1/ regional lymph node metastases, highly differentiated adenocarcinomas and papillary adenocarcinomas. On the contrary, high rates of bone metastases were seen in cancers of the corpus, advanced cancers with invasion to neighbouring structures and tubular adenocarcinomas. Of these 15 patients with bone metastasis, 3 patients showed very similar clinical features and the findings of ''diffuse bone metastases on bone scintigrams.'' Cancer of the antrum showed high rates of liver metastases, while cancers of the corpus showed high rates of bone metastases. Sixty percent of the patients with bone metastases did not have liver metastases and there seemed to be no significant relationship between liver metastases and bone metastases. From these results we suppose that non-portal tract through the vertebral venous plexus instead of portal tract may be the other route of bone metastases from gastric cancer.

Gastric inhibitory polypeptide does not inhibit gastric emptying in humans

DEFF Research Database (Denmark)

Meier, Juris J; Goetze, Oliver; Anstipp, Jens

2004-01-01

) = 0.15, P = 0.15 for intact GIP; r(2) = 0.21, P = 0.086 for total GIP). We conclude that gastric emptying does not appear to be influenced by GIP. The secretion of GIP after meal ingestion is not suppressed by its exogenous administration. The lack of effect of GIP on gastric emptying underlines......The insulinotropic gut hormone gastric inhibitory polypeptide (GIP) has been demonstrated to inhibit gastric acid secretion and was proposed to possess "enterogastrone" activity. GIP effects on gastric emptying have not yet been studied. Fifteen healthy male volunteers (23.9 +/- 3.3 yr, body mass....... Gastric emptying was calculated from the (13)CO(2) exhalation rates in breath samples collected over 360 min. Venous blood was drawn in 30-min intervals for the determination of glucose, insulin, C-peptide, and GIP (total and intact). Statistical calculations were made by use of repeated-measures ANOVA...

PET/CT manifestation of the meniscus sign of ulcerating gastric carcinoma

International Nuclear Information System (INIS)

Bahk, Yong Whee

2007-01-01

Meniscus-like presentation of ulcerating gastric carcinoma on upper gastrointestinal series radiograph was first described in 1921 by Carman and has since been known as a useful differential diagnostic sign in radiology. In 1982 using then newly introduced computed tomography (CT) Widder and Mueller revisited the meniscus sign. Their study was primarily focused on a dynamic assessment of the demonstrability of the meniscus sign that largely depends on the judgment and technical skill of examiner, especially graded compression and patient positioning. One year earlier Balfe et al. assessed the diagnostic reliability of gastric wall thickening as observed on CT scan in adenocarcinoma, lymphoma and leiomyosarcoma and concluded that it is not a reliable finding. In contrast, however, Lee et al. recently emphasized that the wall thickness measurement on CT of exophytic carcinoma, myoma and ulcers was a useful diagnostic means. Thus, it appears that gastric wall thickening or mucosal heave-up is by itself not as reliable as the meniscus sign. The electronic search of world literature failed to disclose earlier report of this sign demonstrated by 18 F-FDG positron emission tomography and computed tomography (PET/CT). The present communication documents 18 F-FDG PET/CT finding of the meniscus sign as encountered in a case of ulcerating gastric carcinoma, the histological diagnosis of which was moderately differentiated tubular adenocarcinoma. Unlike most gastric tumors without ulceration that tend to unimpressively accumulate 18 F-FDG the present case of Borrmann type III gastric carcinoma demonstrated markedly increased 18 F-FDG uptake

Cytoplasmic Drosha Is Aberrant in Precancerous Lesions of Gastric Carcinoma and Its Loss Predicts Worse Outcome for Gastric Cancer Patients.

Science.gov (United States)

Zhang, Hailong; Hou, Yixuan; Xu, Liyun; Zeng, Zongyue; Wen, Siyang; Du, Yan-E; Sun, Kexin; Yin, Jiali; Lang, Lei; Tang, Xiaoli; Liu, Manran

2016-04-01

The nuclear localization of Drosha is critical for its function as a microRNA maturation regulator. Dephosphorylation of Drosha at serine 300 and serine 302 disrupts its nuclear localization, and aberrant distribution of Drosha has been detected in some tumors. The purpose of the present study was to assess cytoplasmic/nuclear Drosha expression in gastric cancer carcinogenesis and progression. Drosha expression and its subcellular location was investigated by immunohistochemical staining of a set of tissue microarrays composed of normal adjacent tissues (374), chronic gastritis (137), precancerous lesions (94), and gastric adenocarcinoma (829) samples, and in gastric cancer cell lines with varying differentiation by immunofluorescence and western blot assay. Gradual loss of cytoplasmic Drosha was accompanied by tumor progression in both gastric cancer tissues and cell lines, and was inversely associated with tumor volume (P = 0.002), tumor grade (P gastric cancer. High levels of cytoplasmic Drosha predicted longer survival (LR = 7.088, P = 0.008) in gastric cancer patients. Our data provide novel insights into gastric cancer that cytoplasmic Drosha potentially plays a role in preventing carcinogenesis and tumor progression, and may be an independent predictor of patient outcome.

Gene Therapy for Human Lung Adenocarcinoma Using a Suicide Gene Driven by a Lung-Specific Promoter Delivered by JC Virus-Like Particles.

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Chun-Nun Chao

Full Text Available Lung adenocarcinoma, the most commonly diagnosed type of lung cancer, has a poor prognosis even with combined surgery, chemotherapy, or molecular targeted therapies. Most patients are diagnosed with an in-operable advanced or metastatic disease, both pointing to the necessity of developing effective therapies for lung adenocarcinoma. Surfactant protein B (SP-B has been found to be overexpressed in lung adenocarcinoma. In addition, it has also been demonstrated that human lung adenocarcinoma cells are susceptible to the JC polyomavirus (JCPyV infection. Therefore, we designed that the JCPyV virus-like particle (VLP packaged with an SP-B promoter-driven thymidine kinase suicide gene (pSPB-tk for possible gene therapy of human lung adenocarcinoma. Plasmids expressing the GFP (pSPB-gfp or thymidine kinase gene (pSPB-tk under the control of the human SP-B promoter were constructed. The promoter's tissue specificity was tested by transfection of pSPB-gfp into A549, CH27, and H460 human lung carcinoma cells and non-lung cells. The JCPyV VLP's gene transfer efficiency and the selective cytotoxicity of pSPB-tk combined with ganciclovir (GCV were tested in vitro and in a xenograft mouse model. In the current study, we found that SP-B promoter-driven GFP was specifically expressed in human lung adenocarcinoma (A549 and large cell carcinoma (H460 cells. JCPyV VLPs were able to deliver a GFP reporter gene into A549 cells for expression. Selective cytotoxicity was observed in A549 but not non-lung cells that were transfected with pSPB-tk or infected with pSPB-tk-carrying JCPyV VLPs. In mice injected with pSPB-tk-carrying JCPyV VLPs through the tail vein and treated with ganciclovir (GCV, a potent 80% inhibition of growth of human lung adenocarcinoma nodules resulted. The JCPyV VLPs combined with the use of SP-B promoter demonstrates effectiveness as a potential gene therapy against human lung adenocarcinoma.

Gene Therapy for Human Lung Adenocarcinoma Using a Suicide Gene Driven by a Lung-Specific Promoter Delivered by JC Virus-Like Particles.

Science.gov (United States)

Chao, Chun-Nun; Lin, Mien-Chun; Fang, Chiung-Yao; Chen, Pei-Lain; Chang, Deching; Shen, Cheng-Huang; Wang, Meilin

2016-01-01

Lung adenocarcinoma, the most commonly diagnosed type of lung cancer, has a poor prognosis even with combined surgery, chemotherapy, or molecular targeted therapies. Most patients are diagnosed with an in-operable advanced or metastatic disease, both pointing to the necessity of developing effective therapies for lung adenocarcinoma. Surfactant protein B (SP-B) has been found to be overexpressed in lung adenocarcinoma. In addition, it has also been demonstrated that human lung adenocarcinoma cells are susceptible to the JC polyomavirus (JCPyV) infection. Therefore, we designed that the JCPyV virus-like particle (VLP) packaged with an SP-B promoter-driven thymidine kinase suicide gene (pSPB-tk) for possible gene therapy of human lung adenocarcinoma. Plasmids expressing the GFP (pSPB-gfp) or thymidine kinase gene (pSPB-tk) under the control of the human SP-B promoter were constructed. The promoter's tissue specificity was tested by transfection of pSPB-gfp into A549, CH27, and H460 human lung carcinoma cells and non-lung cells. The JCPyV VLP's gene transfer efficiency and the selective cytotoxicity of pSPB-tk combined with ganciclovir (GCV) were tested in vitro and in a xenograft mouse model. In the current study, we found that SP-B promoter-driven GFP was specifically expressed in human lung adenocarcinoma (A549) and large cell carcinoma (H460) cells. JCPyV VLPs were able to deliver a GFP reporter gene into A549 cells for expression. Selective cytotoxicity was observed in A549 but not non-lung cells that were transfected with pSPB-tk or infected with pSPB-tk-carrying JCPyV VLPs. In mice injected with pSPB-tk-carrying JCPyV VLPs through the tail vein and treated with ganciclovir (GCV), a potent 80% inhibition of growth of human lung adenocarcinoma nodules resulted. The JCPyV VLPs combined with the use of SP-B promoter demonstrates effectiveness as a potential gene therapy against human lung adenocarcinoma.

Different time trend and management of esophagogastric junction adenocarcinoma in three Asian countries.

Science.gov (United States)

Hatta, Waku; Tong, Daniel; Lee, Yeong Yeh; Ichihara, Shin; Uedo, Noriya; Gotoda, Takuji

2017-04-01

Esophagogastric junction (EGJ) adenocarcinoma has been on the increase in Western countries. However, in Asian countries, data on the incidence of EGJ adenocarcinoma are evidently lacking. In the present review, we focus on the current clinical situation of EGJ adenocarcinoma in three Asian countries: Japan, Hong Kong, and Malaysia. The incidence of EGJ adenocarcinoma has been reported to be gradually increasing in Malaysia and Japan, whereas it has stabilized in Hong Kong. However, the number of cases in these countries is comparatively low compared with Western countries. A reason for the reported difference in the incidence and time trend of EGJ adenocarcinoma among the three countries may be explained by two distinct etiologies: one arising from chronic gastritis similar to distal gastric cancer, and the other related to gastroesophageal reflux disease similar to esophageal adenocarcinoma including Barrett's adenocarcinoma. This review also shows that there are several concerns in clinical practice for EGJ adenocarcinoma. In Hong Kong and Malaysia, many EGJ adenocarcinomas have been detected at a stage not amenable to endoscopic resection. In Japan, histological curability criteria for endoscopic resection cases have not been established. We suggest that an international collaborative study using the same definition of EGJ adenocarcinoma may be helpful not only for clarifying the characteristics of these cancers but also for improving the clinical outcome of these patients. © 2017 The Authors. Digestive Endoscopy © 2017 Japan Gastroenterological Endoscopy Society.

Mucin pattern reflects the origin of the adenocarcinoma in Barrett's esophagus: a retrospective clinical and laboratorial study

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Corbett Carlos

2009-03-01

Full Text Available Abstract Background Mucin immunoexpression in adenocarcinoma arising in Barrett's esophagus (BE may indicate the carcinogenesis pathway. The aim of this study was to evaluate resected specimens of adenocarcinoma in BE for the pattern of mucins and to correlate to the histologic classification. Methods Specimens were retrospectively collected from thirteen patients who underwent esophageal resection due to adenocarcinoma in BE. Sections were scored for the grade of intestinal metaplasia. The tissues were examined by immunohistochemistry for MUC2 and MUC5AC antibodies. Results Eleven patients were men. The mean age was 61 years old (varied from 40 to 75 years old. The tumor size had a mean of 4.7 ± 2.3 cm, and the extension of BE had a mean of 7.7 ± 1.5 cm. Specialized epithelium with intestinal metaplasia was present in all adjacent mucosas. Immunohistochemistry for MUC2 showed immunoreactivity in goblet cells, while MUC5AC was extensively expressed in the columnar gastric cells, localizing to the surface epithelium and extending to a variable degree into the glandular structures in BE. Tumors were classified according to the mucins in gastric type in 7/13 (MUC5AC positive and intestinal type in 4/13 (MUC2 positive. Two tumors did not express MUC2 or MUC5AC proteins. The pattern of mucin predominantly expressed in the adjacent epithelium was associated to the mucin expression profile in the tumors, p = 0.047. Conclusion Barrett's esophagus adenocarcinoma shows either gastric or intestinal type pattern of mucin expression. The two types of tumors developed in Barrett's esophagus may reflect the original cell type involved in the malignant transformation.

Differential growth factor induction and modulation of human gastric epithelial regeneration

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Tetreault, Marie-Pier; Chailler, Pierre; Rivard, Nathalie; Menard, Daniel

2005-01-01

While several autocrine/paracrine growth factors (GFs) can all stimulate epithelial regeneration in experimentally wounded primary gastric cultures, clinical relevance for their non-redundant cooperative actions in human gastric ulcer healing is suggested by the sequential pattern of GF gene induction in vivo. Using new HGE cell lines able to form a coherent monolayer with tight junctions as well as using primary human gastric epithelial cultures, we show that EGF, TGFα, HGF and IGFs accelerate epithelial restitution upon wounding, independently of the TGFβ pathway (as opposed to intestinal cells). However, they differently modulate cell behavior: TGFα exerts strong effects (even more than EGF) on cytoplasmic spreading and non-oriented protruding activity of bordering cells whereas HGF preferentially coordinates single lamella formation, cell elongation and migration into the wound. IGF-I and IGF-II rather induce the alignment of bordering cells and maintain a compact monolayer front. The number of mitotic cells maximally increases with EGF, followed by TGFα and IGF-I,-II. The current study demonstrates that GFs differentially regulate the regeneration of human gastric epithelial cells through specific modulation of cell shape adaptation, migration and proliferation, further stressing that a coordination of GF activities would be necessary for the normal progression of post-wounding epithelial repair

Digital image analysis of HER2 immunohistochemistry in gastric- and oesophageal adenocarcinoma : a validation study on biopsies and surgical specimens

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Koopman, Timco; de Bock, Geertruida H.; Buikema, Henk J.; Smits, Maria M.; Louwen, Maarten; Hage, Mariska; Imholz, Alex L. T.; van der Vegt, Bert

AimsTo test the validity of diagnostics incorporating digital image analysis (DIA) for human epidermal growth factor 2 (HER2) immunohistochemistry (IHC) in gastro-oesophageal adenocarcinomas, as an alternative to current standard diagnostics using manual scoring. Methods and resultsWe included 319

The correlation study of radiological findings with pathological classification of superficial depressed (IIc type) early gastric cancer

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Liu Linxiang; Deng Bingxing; Liu Yujin; Iinuma, G.; Moriyama, N.

2007-01-01

Objective: To investigate the relations between radiological findings and pathological classification of superficial depressed (II c type) early gastric cancer. Methods: Radiological features in subtonic double contrast barium examination and the endoscopic pictures of early gastric cancer compared with the global pathological specimens and micro-pathological features were prospectively studied. Combined with the gastric endoscopic pictures, the sharpness of margin of the lesions, the changes of converging mucosal folds and the changes of the depressed surface on the film of double contrast barium examination were analyzed. The correlation between the radiological features and histological classification of gastric cancer including well differentiated tubular adenocarcinoma (tub1), moderately differentiated tubular adenocarcinoma (tub2), poorly differentiated adenocarcinoma (por) and signet-ring cell carcinoma (sig) were studied. Results: In 102 cases of II c type early gastric cancer, there were tub1 27 cases, tub2 11, por 26 and sig 38 cases histologically. The margin of the depressed lesions of tubl (24 cases) and tub2 (9 cases) cancers were mostly unsharply demarcated or with fine spicular border, while the margin of lesions of por(15 cases) and sig(31 cases) were mostly clearly and sharply demarcated, with statistical significance (P<0.01). The depressed surface of tub1 and tub2 lesions (17 cases) revealed little unevenness, sometimes with evenly granulations, single nodule and scar-like depression, while that of por and sig lesions (41 cases) manifested as nodules of varying sizes, with statistical significance (P<0.01). Conclusion: The radiological findings of superficial depressed early gastric cancer in different histological types were different, the possible histological type could be speculated according to the radiological findings of the lesions. (authors)

Host Epithelial Interactions with Helicobacter Pylori: A Role for Disrupted Gastric Barrier Function in the Clinical Outcome of Infection?

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Andre G Buret

2005-01-01

Full Text Available Infection of the human stomach with Helicobacter pylori may develop into gastritis, ulceration, adenocarcinoma and mucosal lymphomas. The pathogenic mechanisms that determine the clinical outcome from this microbial-epithelial interaction remain poorly understood. An increasing number of reports suggests that disruptions of epithelial barrier function may contribute to pathology and postinfectious complications in a variety of gastrointestinal infections. The aim of this review is to critically discuss the implications of H pylori persistence on gastric disease, with emphasis on the role of myosin light chain kinase, claudins and matrix metalloproteinases in gastric permeability defects, and their contribution to the development of cancer. These mechanisms and the associated signalling events may represent novel therapeutic targets to control disease processes induced by H pylori, a microbial pathogen that colonizes the stomach of over 50% of the human population.

Roentgenological findings in the non-cancerous portion of the stomach with early gastric cancer

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Komatsu, Yukihisa

1987-10-01

Roentgenological findings of the fine reliefs in the non-cancerous portion were studied in 61 patients with early gastric cancer by double contrast examination. Incidence of the various types of the fine reliefs in the non-cancerous portion were as follows;verrucae 4 %, granularity 34 %, fine granularity 58 %, islet 24 %, network 17 % and irregular network 16 %, respectively. Fine granularity and network were observed in 61 % and 46 % of the cases with poorly differentiated adenocarcinoma, respectively. Granularity, fine granularity and irregular network were observed in 30 %, 55 % and 40 % of the cases with signet-ring cell carcinoma, respectively. Granularity, fine granularity and islet were observed in 41 %, 59 % and 30 % of the cases with tubular adenocarcinoma, respectively. These results suggest that fine reliefs in the non-cancerous portion of the stomach with early gastric cancer showed both findings those found in atrophic gastritis (verrucae, granularity, fine granularity and network) and those in gastric cancer (granularity, fine granularity, islet and irregular network).

Roentgenological findings in the non-cancerous portion of the stomach with early gastric cancer

International Nuclear Information System (INIS)

Komatsu, Yukihisa

1987-01-01

Roentgenological findings of the fine reliefs in the non-cancerous portion were studied in 61 patients with early gastric cancer by double contrast examination. Incidence of the various types of the fine reliefs in the non-cancerous portion were as follows ; verrucae 4 %, granularity 34 %, fine granularity 58 %, islet 24 %, network 17 % and irregular network 16 %, respectively. Fine granularity and network were observed in 61 % and 46 % of the cases with poorly differentiated adenocarcinoma, respectively. Granularity, fine granularity and irregular network were observed in 30 %, 55 % and 40 % of the cases with signet-ring cell carcinoma, respectively. Granularity, fine granularity and islet were observed in 41 %, 59 % and 30 % of the cases with tubular adenocarcinoma, respectively. These results suggest that fine reliefs in the non-cancerous portion of the stomach with early gastric cancer showed both findings those found in atrophic gastritis (verrucae, granularity, fine granularity and network) and those in gastric cancer (granularity, fine granularity, islet and irregular network). (author)

Lauren classification and individualized chemotherapy in gastric cancer.

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Ma, Junli; Shen, Hong; Kapesa, Linda; Zeng, Shan

2016-05-01

Gastric cancer is one of the most common malignancies worldwide. During the last 50 years, the histological classification of gastric carcinoma has been largely based on Lauren's criteria, in which gastric cancer is classified into two major histological subtypes, namely intestinal type and diffuse type adenocarcinoma. This classification was introduced in 1965, and remains currently widely accepted and employed, since it constitutes a simple and robust classification approach. The two histological subtypes of gastric cancer proposed by the Lauren classification exhibit a number of distinct clinical and molecular characteristics, including histogenesis, cell differentiation, epidemiology, etiology, carcinogenesis, biological behaviors and prognosis. Gastric cancer exhibits varied sensitivity to chemotherapy drugs and significant heterogeneity; therefore, the disease may be a target for individualized therapy. The Lauren classification may provide the basis for individualized treatment for advanced gastric cancer, which is increasingly gaining attention in the scientific field. However, few studies have investigated individualized treatment that is guided by pathological classification. The aim of the current review is to analyze the two major histological subtypes of gastric cancer, as proposed by the Lauren classification, and to discuss the implications of this for personalized chemotherapy.

Metachronous solitary splenic metastasis arising from early gastric cancer: a case report and literature review.

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Namikawa, Tsutomu; Kawanishi, Yasuhiro; Fujisawa, Kazune; Munekage, Eri; Munekage, Masaya; Sugase, Takahito; Maeda, Hiromichi; Kitagawa, Hiroyuki; Kumon, Tatsuya; Hiroi, Makoto; Kobayashi, Michiya; Hanazaki, Kazuhiro

2017-08-29

The metastasis of malignant tumors to the spleen is rare, and only a small percentage of cases can be treated surgically, as splenic metastases generally occur in the context of multivisceral metastatic cancer at a terminal stage. We report a rare case of metachronous solitary splenic metastasis arising from early gastric cancer. A 75-year-old man was initially referred to our hospital for examination of gastric cancer, diagnosed at a medical check-up. Esophagogastroduodenoscopy showed a slightly elevated lesion with a central irregular depression in the upper-third of the stomach. Biopsy specimens of the lesion showed a moderately-differentiated adenocarcinoma, and abdominal computed tomography showed no evidence of distant metastases. Endoscopic submucosal dissection was performed, with histological confirmation of a moderately-differentiated adenocarcinoma invading the submucosal layer. The patient subsequently underwent laparoscopic total gastrectomy with regional lymph node dissection, resulting in no residual carcinoma and no lymph node metastasis. Computed tomography, 28 months later, showed a well-defined mass measuring 4.2 cm in diameter in the spleen, and the patient underwent a splenectomy, since there was no evidence of further metastatic lesions in any other organs. Histological examination confirmed the diagnosis of a poorly-differentiated adenocarcinoma originating from the previous gastric cancer. The patient was alive 2 months after surgical resection of the splenic metastasis without any recurrence. To the best of our knowledge, this is only the second case of a solitary splenic metastasis from early gastric cancer to be reported in the English literature. The present case suggests surgical resection may be the preferred treatment of choice for patients with a solitary splenic metastasis from gastric cancer.

Human papillomavirus types 16 and 18 in adenocarcinoma of the uterine cervix

International Nuclear Information System (INIS)

Leminen, A.; Paavonen, J.; Vesterinen, E.; Wahlstroem, T.R.; Rantala, I.; Lehtinen, M.

1991-01-01

Many reports have shown a link between human papillomavirus (HPV) and cervical squamous neoplasia. However, the association of HPV with cervical adenocarcinoma has been studied less extensively. The authors evaluated the presence of HPV-DNA in 106 patients with adenocarcinoma of the uterine cervix by in situ hybridization, using 35 S-labeled probes for HPV 16 DNA and HPV 18 DNA. The overall prevalence of HPV-DNA was 18% (19 of 106). HPV 16 was present in 2 (2%) cases, HPV 18 was observed in 15 (14%) cases, and both HPV 16 and HPV 18 were found in 2 (2%) cases. There was a correlation between HPV-DNA positivity and tumor stage (P less than 0.01) and tumor size (P less than 0.05), but there was no relationship between HPV-DNA positivity and tumor differentiation, proliferation (S-phase fraction), ploidy, lymph node metastases, or five-year survival rate. These results suggest that HPV 18 DNA is associated with cervical adenocarcinoma but the presence of HPV 18 has no influence on overall survival

Clinical studies on gastric cancer and breast cancer among A-bomb survivors

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Yamagata, S; Ohya, M; Nagusa, Y; Harada, T; Tani, T [Hiroshima Univ. (Japan). Research Inst. for Nuclear Medicine and Biology

1977-04-01

Fifty-five cases of gastric cancer and 14 cases of breast cancer among A-Bomb survivors, which had been treated at Dept. of Surgery, Research Institute for Nuclear Medicine and Biology of Hiroshima Univ., were discussed. Both gastric cancer and breast cancer were recognized more in A-Bomb survivors of advanced age. Particularly, the number of gastric cancer in A-Bomb survivors of over 65-year old was about double the number of unexposed persons. Ratio of male to female in A-Bomb survivors with gastric cancer was 1.6:1, and the ratio of female was higher as compared to the ratio in unexposed persons (2.6:1). Gastric cancer of stage III and IV in A-Bomb survivors was 54.5%, and advanced cancer was comparatively few in A-Bomb survivors as compared to in unexposed persons (78.2%). Similarly, comparatively early stage breast cancer of stage I and II was recognized more in A-Bomb survivors. Particularly, T/sub 1/ and T/sub 2/ in which tumor was small in size showed very high percentage of 92.9% in A-Bomb survivors. In gastric cancer in A-Bomb survivors, poorly differentiated adenocarcinoma showed the highest percentage of 34.5%. However, there was no significant difference according to the exposure conditions. As to histological type of breast cancer, medullary tubular adenocarcinoma abounds mostly in both A-Bomb survivors (71.4%) and unexposed persons (75.9%). As the influence of operation, anemia was recognized before operation strongly in A-Bomb survivors with gastric cancer of over 65-year old. After the operation, transient rise of GOT and GPT was recognized in A-Bomb survivors of advanced age with gastric cancer. However, there was no difference in postoperative complications between A-Bomb survivors and unexposed persons.

Molecular Characterization of the Human Stomach Microbiota in Gastric Cancer Patients

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Guoqin Yu

2017-07-01

Full Text Available Helicobacter pylori (Hp is the primary cause of gastric cancer but we know little of its relative abundance and other microbes in the stomach, especially at the time of gastric cancer diagnosis. Here we characterized the taxonomic and derived functional profiles of gastric microbiota in two different sets of gastric cancer patients, and compared them with microbial profiles in other body sites. Paired non-malignant and tumor tissues were sampled from 160 gastric cancer patients with 80 from China and 80 from Mexico. The 16S rRNA gene V3–V4 region was sequenced using MiSeq platform for taxonomic profiles. PICRUSt was used to predict functional profiles. Human Microbiome Project was used for comparison. We showed that Hp is the most abundant member of gastric microbiota in both Chinese and Mexican samples (51 and 24%, respectively, followed by oral-associated bacteria. Taxonomic (phylum-level profiles of stomach microbiota resembled oral microbiota, especially when the Helicobacter reads were removed. The functional profiles of stomach microbiota, however, were distinct from those found in other body sites and had higher inter-subject dissimilarity. Gastric microbiota composition did not differ by Hp colonization status or stomach anatomic sites, but did differ between paired non-malignant and tumor tissues in either Chinese or Mexican samples. Our study showed that Hp is the dominant member of the non-malignant gastric tissue microbiota in many gastric cancer patients. Our results provide insights on the gastric microbiota composition and function in gastric cancer patients, which may have important clinical implications.

Identification of molecular subtypes of gastric cancer with different responses to PI3-kinase inhibitors and 5-fluorouracil.

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Lei, Zhengdeng; Tan, Iain Beehuat; Das, Kakoli; Deng, Niantao; Zouridis, Hermioni; Pattison, Sharon; Chua, Clarinda; Feng, Zhu; Guan, Yeoh Khay; Ooi, Chia Huey; Ivanova, Tatiana; Zhang, Shenli; Lee, Minghui; Wu, Jeanie; Ngo, Anna; Manesh, Sravanthy; Tan, Elisabeth; Teh, Bin Tean; So, Jimmy Bok Yan; Goh, Liang Kee; Boussioutas, Alex; Lim, Tony Kiat Hon; Flotow, Horst; Tan, Patrick; Rozen, Steven G

2013-09-01

Almost all gastric cancers are adenocarcinomas, which have considerable heterogeneity among patients. We sought to identify subtypes of gastric adenocarcinomas with particular biological properties and responses to chemotherapy and targeted agents. We compared gene expression patterns among 248 gastric tumors; using a robust method of unsupervised clustering, consensus hierarchical clustering with iterative feature selection, we identified 3 major subtypes. We developed a classifier for these subtypes and validated it in 70 tumors from a different population. We identified distinct genomic and epigenomic properties of the subtypes. We determined drug sensitivities of the subtypes in primary tumors using clinical survival data, and in cell lines through high-throughput drug screening. We identified 3 subtypes of gastric adenocarcinoma: proliferative, metabolic, and mesenchymal. Tumors of the proliferative subtype had high levels of genomic instability, TP53 mutations, and DNA hypomethylation. Cancer cells of the metabolic subtype were more sensitive to 5-fluorouracil than the other subtypes. Furthermore, in 2 independent groups of patients, those with tumors of the metabolic subtype appeared to have greater benefits with 5-fluorouracil treatment. Tumors of the mesenchymal subtype contain cells with features of cancer stem cells, and cell lines of this subtype are particularly sensitive to phosphatidylinositol 3-kinase-AKT-mTOR inhibitors in vitro. Based on gene expression patterns, we classified gastric cancers into 3 subtypes, and validated these in an independent set of tumors. The subgroups have differences in molecular and genetic features and response to therapy; this information might be used to select specific treatment approaches for patients with gastric cancer. Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.

[A case of metastatic gastric cancer originating from transverse colon cancer].

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Nushijima, Youichirou; Nakano, Katsutoshi; Sugimoto, Keishi; Nakaguchi, Kazunori; Kan, Kazuomi; Maruyama, Hirohide; Doi, Sadayuki; Okamura, Shu; Murata, Kohei

2014-11-01

Metastatic gastric cancer is uncommon, and metastasis of colorectal cancer to the stomach is extremely rare. We report a case of metastatic gastric cancer that originated from transverse colon cancer. A 52-year-old woman underwent a left hemicolectomy and D3 lymph node dissection based on a diagnosis of transverse colon cancer. The pathology results were as follows: mucinous adenocarcinoma, type 2, 6 × 11 cm, ss, ly1 v1, pm (-), dm (-), n1 (+), P0, H0, M0, Stage IIIa. The patient received XELOX as postoperative adjuvant therapy for 6 months. One year and 3 months after the left hemicolectomy, gastroscopy revealed a submucosal tumor in the lower body of the stomach and an incipient cancer in the cardia of the stomach, and a colonoscopy revealed an incipient cancer in the transverse colon. An endoscopic ultrasonography fine needle aspiration biopsy of the submucosal tumor in the lower body of the stomach was performed. Histology showed that this tumor was a mucinous adenocarcinoma similar to the primary transverse colon cancer, which led to a diagnosis of metastatic gastric cancer originating from transverse colon cancer. Distant metastasis was not detected. Endoscopic submucosal dissection of the incipient gastric cancer was performed, as were distal gastrectomy and partial colectomy. Peritoneal dissemination and para-aortic lymph node recurrence were detected 7 months after the second surgery.

Nuclear Pattern of CXCR4 Expression Is Associated with a Better Overall Survival in Patients with Gastric Cancer

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Bahram Nikkhoo

2014-01-01

Full Text Available Introduction. Previous studies have shown that stromal-derived factor-1 (CXCL12 and its receptor, CXCR4, play a crucial role in metastasis of various tumors. Similarly, it has been cleared that CXCR4 is expressed on the cell surface of gastric cancers. However, nuclear expression of CXCR4 and its clinical importance have not been yet studied. Materials and Methods. Herein, we studied the expression of CXCR4 in gastric samples from patients with gastric adenocarcinoma as well as human gastric carcinoma cell line, AGS, by employing RT-PCR, immunohistochemistry, and flow cytometry techniques. Results. RT-PCR data showed that CXCR4 is highly expressed on AGS cells. This was confirmed by IHC and FACS as CXCR4 was detected on cell membrane, in cytoplasm, and in nucleus of AGS cells. Moreover, we found that both cytoplasmic and nuclear CXCR4 are strongly expressed in primary gastric cancer and the cytoplasmic pattern of CXCR4 tends to be associated with a shorter overall survival than nuclear staining. In conclusion, we present evidence for the first time that both cytoplasmic and nuclear expression of CXCR4 are detectable in gastric cancer tissues. However, the role of both cytoplasmic and nuclear CXCR4 needs to be further elucidated.

Human Gastric Mucosal Hydrophobicity Does dot Decrease with Helicobacter Pylori Infection or Chronological Age

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Mohammed S Al-Marhoon

2005-01-01

Full Text Available BACKGROUND AND AIMS: Infection with cytotoxin-associated gene A (cagA Helicobacter pylori is associated with severe gastric diseases. Previous studies in humans have reported a decreased gastric hydrophobicity with H pylori infection. The aim of the present study was to differentiate between the effect of cagA+ and cagA- strains on gastric mucus hydrophobicity.

Gastric adenocarcinoma screening and prevention in the era of new biomarker and endoscopic technologies: a cost-effectiveness analysis.

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Yeh, Jennifer M; Hur, Chin; Ward, Zachary; Schrag, Deborah; Goldie, Sue J

2016-04-01

To estimate the cost-effectiveness of noncardia gastric adenocarcinoma (NCGA) screening strategies based on new biomarker and endoscopic technologies. Using an intestinal-type NCGA microsimulation model, we evaluated the following one-time screening strategies for US men: (1) serum pepsinogen to detect gastric atrophy (with endoscopic follow-up of positive screen results), (2) endoscopic screening to detect dysplasia and asymptomatic cancer (with endoscopic mucosal resection (EMR) treatment for detected lesions) and (3) Helicobacter pylori screening and treatment. Screening performance, treatment effectiveness, cancer and cost data were based on published literature and databases. Subgroups included current, former and never smokers. Outcomes included lifetime cancer risk and incremental cost-effectiveness ratios (ICERs), expressed as cost per quality-adjusted-life-year (QALY) gained. Screening the general population at age 50 years reduced the lifetime intestinal-type NCGA risk (0.24%) by 26.4% with serum pepsinogen screening, 21.2% with endoscopy and EMR and 0.2% with H. pylori screening/treatment. Targeting current smokers reduced the lifetime risk (0.35%) by 30.8%, 25.5%, and 0.1%, respectively. For all subgroups, serum pepsinogen screening was more effective and more cost-effective than all other strategies, although its ICER varied from $76,000/QALY (current smokers) to $105,400/QALY (general population). Results were sensitive to H. pylori prevalence, screen age and serum pepsinogen test sensitivity. Probabilistic sensitivity analysis found that at a $100,000/QALY willingness-to-pay threshold, the probability that serum pepsinogen screening was preferred was 0.97 for current smokers. Although not warranted for the general population, targeting high-risk smokers for serum pepsinogen screening may be a cost-effective strategy to reduce intestinal-type NCGA mortality. Published by the BMJ Publishing Group Limited. For permission to use (where not already

Immunohistochemical investigations of xenotransplanted human adenocarcinomas on nude mice: Correlation to radioimaging

International Nuclear Information System (INIS)

Matejkova, E.

1987-01-01

Immunohistochemical investigations of xenotransplanted human adenocarcinomas on nude mice; correlation to radioimaging Human carcinomas were subcutanously grafted to nude mice (Balb/c-nu/nu) and were investigated in four passages by immunohistochemical methods and by the fluorochrome bisbenzimid. In this way there could be observed a successful differentiation between the nourishing murine stroma and the human tumor parenchym. Especially the use of a monoclonal antibody (rat/mouse fusion) directed against human tissue turned out to be a suitable method. Four adenocarcinomas were tested: Colon-, mamma-, stomach- and testicle carcinoma. During the first four passages atypical parts of murine connective tissue and some changes in the human parenchyma could be seen. These results demonstrate that also in nude mice variations of the transplanted tumor material could happen. They could be detected in time with a routine immunohistochemical test. The consequences of tumor morphological variations for the development of therapeutic and diagnostic tools were studied with the help of radioimaging by external scintigraphy. Furthermore the biodistribution, tumoruptake and the whole body counting were studied by means of radionuclid marked monoclonal antibodies. The morphological variations of the passages of mammary, testicle and colon carcinomas were not big enough to influence the results in a certain way. Therefore especially the relation between the activity uptake in the tissue, the size of the tumor and the whole body uptake was studied in view of immunoscintigraphy. (orig./MG) [de

The role of propranolol as a radiosensitizer in gastric cancer treatment

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Liao XH

2018-03-01

Full Text Available Xinhua Liao, Prakash Chaudhary, Guanglin Qiu, Xiangming Che, Lin Fan General Surgery Department, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China Purpose: The National Comprehensive Cancer Network guidelines indicate that radiotherapy in gastric cancer shows limited effectiveness at reducing the growth of gastric cancer. Therefore, enhancing the sensitivity and effect of radiotherapy with propranolol, a β-adrenoceptor antagonist, could reduce tumor growth. The role of propranolol as a radiosensitizer has not been adequately studied; therefore, the purpose of the present study is to evaluate the effect of propranolol as a radiosensitizer against gastric cancer in vivo. Methods: Sixty-four male nude mice bearing tumor xenografts were randomly divided into four groups. Cell culture was performed using the human gastric adenocarcinoma cell line SGC-7901. Mice with tumor xenografts were treated with propranolol, isoproterenol, and radiation. The data for tumor weight and volume were obtained for statistical analyses. Furthermore, the expression levels of COX-2, NF-κB, VEGF, and EGFR were examined using immunohistochemical techniques and Western blotting.Results: The growth in the volume and weight of the tumor was lower in mouse models treated with propranolol and radiation therapy compared to the other groups. Decreased expression of NF-κB was also observed in treatment groups where both propranolol and radiation were used, leading to the reduction of COX-2, EGFR, and VEGF expression compared to that in the other groups.Conclusion: The present study indicated that propranolol potentiates the antitumor effects of radiotherapy in gastric cancer by inhibiting NF-κB expression and its downstream genes: VEGF, EGFR, and COX-2. Keywords: propranolol, radiosensitizer, gastric cancer, radiation therapy 

Polymorphisms in metabolic genes related to tobacco smoke and the risk of gastric cancer in the European prospective investigation into cancer and nutrition

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Agudo, Antonio; Sala, Núria; Pera, Guillem; Capellá, Gabriel; Berenguer, Antonio; García, Nadia; Palli, Domenico; Boeing, Heiner; del Giudice, Giuseppe; Saieva, Calogero; Carneiro, Fatima; Berrino, Franco; Sacerdote, Carlotta; Tumino, Rosario; Panico, Salvatore; Berglund, Göran; Simán, Henrik; Stenling, Roger; Hallmans, Göran; Martínez, Carmen; Bilbao, Roberto; Barricarte, Aurelio; Navarro, Carmen; Quirós, José R.; Allen, Naomi; Key, Tim; Bingham, Sheila; Khaw, Kay-Tee; Linseisen, Jakob; Nagel, Gabriele; Overvad, Kim; Tjonneland, Anne; Olsen, Anja; Bueno-de-Mesquita, H. Bas; Boshuizen, Hendriek C.; Peeters, Petra H.; Numans, Mattijs E.; Clavel-Chapelon, Françoise; Boutron-Ruault, Marie-Christine; Trichopoulou, Antonia; Lund, Eiliv; Offerhaus, Johan; Jenab, Mazda; Ferrari, Pietro; Norat, Teresa; Riboli, Elio; González, Carlos A.

2006-01-01

Metabolizing enzymes, which often display genetic polymorphisms, are involved in the activation of compounds present in tobacco smoke that may be relevant to gastric carcinogenesis. We report the results of a study looking at the association between risk of gastric adenocarcinoma and polymorphisms

The rare presentations of a large polyp and an esophageal carcinoma in heterotropic gastric mucosa: a case series

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Alagozlu Hakan

2007-11-01

Full Text Available Abstract Background Heterotopic gastric mucosa (HGM is commonly seen in the upper esophagus during endoscopyand is generally considered a benign disease. A hyperplastic polyp and an adenocarcinoma arising in heterotopic gastric mucosa are quite rare occurences. Case presentations We present two cases: The first is a patient who suffered from dysphagia because of a large hyperplastic polyp that arose from HGM; the polyp was excised endoscopically. Secondly, we report a rare case of adenocarcinoma arising in HGM of the cervical esophagus. Conclusion Morphologic changes or malignant transformation can develop in the inlet patch. Therefore, gastroenterologists should be aware of the possibility of HGM just distal to the upper esophageal sphincter.

The Outlet Patch: Gastric Heterotopia of the Colo-rectum and Anus.

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Mannan, Abul Ala Syed Rifat; Vieth, Michael; Khararjian, Armen; Khandakar, Binny; Lam-Himlin, Dora; Heydt, David; Bhaijee, Feriyl; Venbrux, Henry J; Byrnes, Kathleen; Voltaggio, Lysandra; Barker, Norman; Yuan, Songyang; Montgomery, Elizabeth

2018-04-18

Gastric heterotopia (GH) has been described throughout the gastrointestinal tract. However, the colorectal region is an extremely rare location for it. We describe the clinicopathologic features of GH of the colon, rectum, and anus. We identified 33 cases in 20 males and 13 females (median age 54 years; range, 4 months to 73 years). Sites included the rectum (N=26), anus (N=4), ileocecal junction (N=1), ascending colon (N=1) and descending colon (N=1). Presenting symptoms(N=27) included hematochezia (41%) and altered bowel habits (4%); 15 patients (55%) were asymptomatic. On colonoscopy (N=31), all appeared as solitary lesions, (median size 6.5 mm, range 2 mm - 55 mm), either as polyps (61%), raised erythematous patches (23%), an ulcer(10%), within a rectal diverticulum (3%), or a hemorrhoid (3%). Patients were managed by polypectomy. One with an associated carcinoma in the area of GH underwent resection. No morbidity related to GH itself was reported following excision. Histologically, heterotopic gastric mucosa was oxyntic type (85%), mixed oxyntic and non-oxyntic type (12%), and not specified (3%). In 5 patients a pyloric gland adenoma (PGA) arose from heterotopic gastric mucosa, two of which contained a focus of invasive adenocarcinoma. One case had associated surface foveolar type low-grade dysplasia. Another had associated adenocarcinoma arising from the heterotopic mucosa. One example harbored Helicobacter pylori organisms. We highlight the features of GH in the distal GIT - the 'outlet patch'. Association with PGA, surface dysplasia and adenocarcinoma suggests that lower tract GH can undergo neoplastic transformation. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Iron overload of human colon adenocarcinoma cells studied by synchrotron-based X-ray techniques

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Mihucz, Victor G.; Meirer, Florian; Polgári, Zsófia; Réti, Andrea; Pepponi, Giancarlo; Ingerle, Dieter; Szoboszlai, Norbert; Streli, Christina

2016-01-01

Fast- and slow-proliferating human adenocarcinoma colorectal cells, HT-29 and HCA-7, respectively, overloaded with transferrin (Tf), Fe(III) citrate, Fe(III) chloride and Fe(II) sulfate were studied by synchrotron radiation total-reflection X-ray spectrometry (TXRF), TXRF-X-ray absorption near edge

Comparison of global gene expression of gastric cardia and noncardia cancers from a high-risk population in china.

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Gangshi Wang

Full Text Available To profile RNA expression in gastric cancer by anatomic subsites as an initial step in identifying molecular subtypes and providing targets for early detection and therapy.We performed transcriptome analysis using the Affymetrix GeneChip U133A in gastric cardia adenocarcinomas (n = 62 and gastric noncardia adenocarcinomas (n = 72 and their matched normal tissues from patients in Shanxi Province, and validated selected dysregulated genes with additional RNA studies. Expression of dysregulated genes was also related to survival of cases.Principal Component Analysis showed that samples clustered by tumor vs. normal, anatomic location, and histopathologic features. Paired t-tests of tumor/normal tissues identified 511 genes whose expression was dysregulated (P<4.7E-07 and at least two-fold difference in magnitude in cardia or noncardia gastric cancers, including nearly one-half (n = 239, 47% dysregulated in both cardia and noncardia, one-fourth dysregulated in cardia only (n = 128, 25%, and about one-fourth in noncardia only (n = 144, 28%. Additional RNA studies confirmed profiling results. Expression was associated with case survival for 20 genes in cardia and 36 genes in noncardia gastric cancers.The dysregulated genes identified here represent a comprehensive starting point for future efforts to understand etiologic heterogeneity, develop diagnostic biomarkers for early detection, and test molecularly-targeted therapies for gastric cancer.

Predictive value of CHFR and MLH1 methylation in human gastric cancer.

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Li, Yazhuo; Yang, Yunsheng; Lu, Youyong; Herman, James G; Brock, Malcolm V; Zhao, Po; Guo, Mingzhou

2015-04-01

Gastric carcinoma (GC) has one of the highest mortality rates of cancer diseases and has a high incidence rate in China. Palliative chemotherapy is the main treatment for advanced gastric cancer. It is necessary to compare the effectiveness and toxicities of different regimens. This study explores the possibility of methylation of DNA damage repair genes serving as a prognostic and chemo-sensitive marker in human gastric cancer. The methylation status of five DNA damage repair genes (CHFR, FANCF, MGMT, MLH1, and RASSF1A) was detected by nested methylation-specific PCR in 102 paraffin-embedded gastric cancer samples. Chi-square or Fisher's exact tests were used to evaluate the association of methylation status and clinic-pathological factors. The Kaplan-Meier method and Cox proportional hazards models were employed to analyze the association of methylation status and chemo-sensitivity. The results indicate that CHFR, MLH1, RASSF1A, MGMT, and FANCF were methylated in 34.3% (35/102), 21.6% (22/102), 12.7% (13/102), 9.8% (10/102), and 0% (0/102) of samples, respectively. No association was found between methylation of CHFR, MLH1, RASSF1A, MGMT, or FANCF with gender, age, tumor size, tumor differentiation, lymph node metastasis, and TNM stage. In docetaxel-treated gastric cancer patients, resistance to docetaxel was found in CHFR unmethylated patients by Cox proportional hazards model (HR 0.243, 95% CI, 0.069-0.859, p = 0.028), and overall survival is longer in the CHFR methylated group compared with the CHFR unmethylated group (log-rank, p = 0.036). In oxaliplatin-treated gastric cancer patients, resistance to oxaliplatin was found in MLH1 methylated patients (HR 2.988, 95% CI, 1.064-8.394, p = 0.038), and overall survival was longer in the MLH1 unmethylated group compared with the MLH1 methylated group (log-rank, p = 0.046). CHFR is frequently methylated in human gastric cancer, and CHFR methylation may serve as a docetaxel-sensitive marker. MLH1 methylation was

Tissue metabolic profiling of human gastric cancer assessed by 1H NMR

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Wang, Huijuan; Zhang, Hailong; Deng, Pengchi; Liu, Chunqi; Li, Dandan; Jie, Hui; Zhang, Hu; Zhou, Zongguang; Zhao, Ying-Lan

2016-01-01

Gastric cancer is the fourth most common cancer and the second most deadly cancer worldwide. Study on molecular mechanisms of carcinogenesis will play a significant role in diagnosing and treating gastric cancer. Metabolic profiling may offer the opportunity to understand the molecular mechanism of carcinogenesis and help to identify the potential biomarkers for the early diagnosis of gastric cancer. In this study, we reported the metabolic profiling of tissue samples on a large cohort of human gastric cancer subjects (n = 125) and normal controls (n = 54) based on 1 H nuclear magnetic resonance ( 1 H NMR) together with multivariate statistical analyses (PCA, PLS-DA, OPLS-DA and ROC curve). The OPLS-DA model showed adequate discrimination between cancer tissues and normal controls, and meanwhile, the model excellently discriminated the stage-related of tissue samples (stage I, 30; stage II, 46; stage III, 37; stage IV, 12) and normal controls. A total of 48 endogenous distinguishing metabolites (VIP > 1 and p < 0.05) were identified, 13 of which were changed with the progression of gastric cancer. These modified metabolites revealed disturbance of glycolysis, glutaminolysis, TCA, amino acids and choline metabolism, which were correlated with the occurrence and development of human gastric cancer. The receiver operating characteristic diagnostic AUC of OPLS-DA model between cancer tissues and normal controls was 0.945. And the ROC curves among different stages cancer subjects and normal controls were gradually improved, the corresponding AUC values were 0.952, 0.994, 0.998 and 0.999, demonstrating the robust diagnostic power of this metabolic profiling approach. As far as we know, the present study firstly identified the differential metabolites in various stages of gastric cancer tissues. And the AUC values were relatively high. So these results suggest that the metabolic profiling of gastric cancer tissues has great potential in detecting this disease and helping

Correlação da infiltração das células Natural Killer (NK CD 57+ no prognóstico do adenocarcinoma gástrico Gástrico correlation of Natural Killer cell with the prognosis of gastric adenocarcinoma

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Déborah Rosso

2012-06-01

Full Text Available OBJETIVO: Avaliar a concentração da célula Natural Killer (NK no adenocarcinoma gástrico operado, e sua correlação com fatores prognósticos e sobrevida MÉTODOS: Foram estudados 72 doentes portadores de adenocarcinoma gástrico e que foram submetidos à gastrectomia com linfadenectomia D2. A concentração de célula NK foi avaliada por técnica de imunoistoquímica pelo reagente CD57. Os doentes foram divididos em dois grupos: alta concentração de células (n=32 (>15 células /10 campos de grande aumento e baixa concentração (≤ 15 células/10 campos de grande aumento. Esses dois grupos foram comparados com seguintes fatores prognósticos: gênero, idade, localização do tumor, grau de diferenciação celular, classificação de Lauren, estádio, disseminação linfática, metástases e sobrevida. A curva de Kaplan-Meier foi empregada para avaliação de sobrevida e a análise multivariada para avaliação dos fatores prognósticos. RESULTADOS: Não houve relação das células NK com as diversas variáveis estudadas, a não ser com o estádio, onde houve significância (pAIM: To evaluate the concentration of Natural Killer cells (NK cells in adenocarcinoma of the stomach, and its correlation with prognostic factors and survival. METHODS: Seventy-two patients with gastric adenocarcinoma who underwent gastric resection surgery and D2 lymphadenectomy in the period 1997-2007 were analyzed. The concentration of NK cells was evaluated by immunohistochemistry technique with the reagent CD57. Patients were divided into two groups: high concentration (n = 32 (more than 15 cells per 10 high power field and low concentration (less or equal than 15 cells per 10 high power field. These two groups were compared with several prognostic factors such as: gender, age, tumor location, tumor differentiation, Lauren classification, stage, lymph nodes involvement, distant metastases and survival. The Kaplan-Meier curve was applied to evaluate survival

Intraneural metastasis of gastric carcinoma leads to sciatic nerve palsy

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Ichikawa, Jiro; Matsumoto, Seiichi; Shimoji, Takashi; Tanizawa, Taisuke; Gokita, Tabu; Hayakawa, Keiko; Aoki, Kaoru; Ina, Saori; Kanda, Hiroaki

2012-01-01

Soft tissue metastases, in particular intraneural metastasis, from any carcinomas seldom occur. To our knowledge, no case of sciatic nerve palsy due to intraneural metastasis of gastric carcinoma is reported in the literature. A case is reported of a 82-year old woman with sciatic nerve palsy with intraneural metastasis of gastric carcinoma. Although she had undergone partial gastrectomy with T2b, N0, M0 two years ago and primary site was cured, she developed sciatic nerve palsy from the carcinoma metastasis directly to the nerve. Operative resection and Histological examination revealed poorly differentiated adenocarcinoma, the same as her primary site adenocarcinoma. Sciatica is usually caused by a herniated disc or spinal canal stenosis. Sciatic nerve palsy may be caused by nondiscogenic etiologies that may be either intrapelvic or extrapelvic. It is important to image the entire course of the nerve to distinguish these etiologies quickly. The longer the nerve compression the less likely a palsy will recover. Surgery is a good intervention that simultaneously obtains a tissue diagnosis and decompresses the nerve

Assessment of cytotoxicity of Portulaca oleracea Linn. against human colon adenocarcinoma and vero cell line

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Mali, Prashant Y.

2015-01-01

Background: Portulaca oleracea Linn. (Portulacaceae) is commonly known as purslane in English. In traditional system it is used to cure diarrhea, dysentery, leprosy, ulcers, asthma, and piles, reduce small tumors and inflammations. Aim: To assess cytotoxic potential of chloroform extract of P. oleracea whole plant against human colon adenocarcinoma (HCT-15) and normal (Vero) cell line. Materials and Methods: Characterization of chloroform extract of P. oleracea by Fourier transform infrared (FTIR) spectroscopy was performed. Cytotoxicity (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide) assay was used for assessment of cytotoxic potential of chloroform extract of P. oleracea. The concentrations of 1000–0.05 μg/ml were used in the experiment. Doxorubicin was considered as standard reference drug. Results: FTIR spectrum showed the peak at 1019.52 and 1396.21 center. The 50% cell growth inhibition (IC50) of chloroform extract of P. oleracea and doxorubicin was 1132.02 μg/ml and 460.13 μg/ml against human colon adenocarcinoma and 767.60 μg/ml and 2392.71 μg/ml against Vero cell line, respectively. Conclusion: Chloroform extract of P. oleracea whole plant was less efficient or does not have cytotoxic activity against human colon adenocarcinoma cell line. It was not safe to normal Vero cell line. But, there is a need to isolate, identify, and confirm the phytoconstituents present in extract by sophisticated analytical techniques. PMID:27833374

Impact of human milk pasteurization on gastric digestion in preterm infants: a randomized controlled trial.

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de Oliveira, Samira C; Bellanger, Amandine; Ménard, Olivia; Pladys, Patrick; Le Gouar, Yann; Dirson, Emelyne; Kroell, Florian; Dupont, Didier; Deglaire, Amélie; Bourlieu, Claire

2017-02-01

Holder pasteurization has been reported to modify human milk composition and structure by inactivating bile salt-stimulated lipase (BSSL) and partially denaturing some of its proteins, potentially affecting its subsequent digestion. We sought to determine the impact of human milk pasteurization on gastric digestion (particularly for proteins and lipids) in preterm infants who were fed their mothers' own milk either raw or pasteurized. In a randomized controlled trial, 12 hospitalized tube-fed preterm infants were their own control group in comparing the gastric digestion of raw human milk (RHM) with pasteurized human milk (PHM). Over a 6-d sequence, gastric aspirates were collected 2 times/d before and after RHM or PHM ingestion. The impact of milk pasteurization digestive kinetics and disintegration was tested with the use of a general linear mixed model. Despite inactivating BSSL, instantaneous lipolysis was not affected by pasteurization (mean ± SD at 90 min: 12.6% ± 4.7%; P > 0.05). Lipolysis occurred in milk before digestion and was higher for PHM than for RHM (mean ± SD: 3.2% ± 0.6% and 2.2% ± 0.8%, respectively; P Pasteurization enhanced the proteolysis of lactoferrin (P Pasteurization did not affect gastric emptying (∼30-min half time) or pH (mean ± SD: 4.4 ± 0.8) at 90 min. Overall, pasteurization had no impact on the gastric digestion of lipids and some proteins from human milk but did affect lactoferrin and α-lactalbumin proteolysis and emulsion disintegration. Freeze-thawing and pasteurization increased the milk lipolysis before digestion but did not affect gastric lipolysis. Possible consequences on intestinal digestion and associated nutritional outcomes were not considered in this study. This trial was registered at clinicaltrials.gov as NCT02112331. © 2017 American Society for Nutrition.

β-Elemene-induced autophagy protects human gastric cancer cells from undergoing apoptosis

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Liu, Jing; Zhang, Ye; Qu, Jinglei; Xu, Ling; Hou, Kezuo; Zhang, Jingdong; Qu, Xiujuan; Liu, Yunpeng

2011-01-01

β-Elemene, a compound found in an herb used in traditional Chinese medicine, has shown promising anti-cancer effects against a broad spectrum of tumors. The mechanism by which β-elemene kills cells remains unclear. The aim of the present study is to investigate the anti-tumor effect of β-elemene on human gastric cancer cells and the molecular mechanism involved. β-Elemene inhibited the viability of human gastric cancer MGC803 and SGC7901 cells in a dose-dependent manner. The suppression of cell viability was due to the induction of apoptosis. A robust autophagy was observed in the cells treated with β-elemene; it was characterized by the increase of punctate LC3 dots, the cellular morphology, and the increased levels of LC3-II protein. Further study showed that β-elemene treatment up-regulated Atg5-Atg12 conjugated protein but had little effect on other autophagy-related proteins. PI3K/Akt/mTOR/p70S6K1 activity was inhibited by β-elemene. Knockdown of Beclin 1 with small interfering RNA, or co-treatment with the autophagy inhibitor, 3-methyladenine or chlorochine enhanced significantly the antitumor effects of β-elemene. Our data provides the first evidence that β-elemene induces protective autophagy and prevents human gastric cancer cells from undergoing apoptosis. A combination of β-elemene with autophagy inhibitor might thus be a useful therapeutic option for advanced gastric cancer

ERC/mesothelin is expressed in human gastric cancer tissues and cell lines.

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Ito, Tomoaki; Kajino, Kazunori; Abe, Masaaki; Sato, Koichi; Maekawa, Hiroshi; Sakurada, Mutsumi; Orita, Hajime; Wada, Ryo; Kajiyama, Yoshiaki; Hino, Okio

2014-01-01

ERC/mesothelin is expressed in mesothelioma and other malignancies. The ERC/mesothelin gene (MSLN) encodes a 71-kDa precursor protein, which is cleaved to yield 31-kDa N-terminal (N-ERC/mesothelin) and 40-kDa C-terminal (C-ERC/mesothelin) proteins. N-ERC/mesothelin is a soluble protein and has been reported to be a diagnostic serum marker of mesothelioma and ovarian cancer. Gastric cancer tissue also expresses C-ERC/mesothelin, but the significance of serum N-ERC levels for diagnosing gastric cancer has not yet been studied. We examined the latter issue in the present study as well as C-ERC/mesothelin expression in human gastric cancer tissues and cell lines. We immunohistochemically examined C-ERC/mesothelin expression in tissue samples from 50 cases of gastric cancer, and we also assessed the C-ERC/mesothelin expression in 6 gastric cancer cell lines (MKN-1, MKN-7, MKN-74, NUGC-3, NUGC-4 and TMK-1) using reverse transcription-polymerase chain reaction, flow cytometry, immunohistochemistry and immunoblotting. We also examined the N-ERC/mesothelin concentrations in the supernatants of cultured cells and in the sera of gastric cancer patients using an enzyme-linked immunosorbent assay (ELISA). N-ERC/mesothelin was detected in the supernatants of 3 gastric cancer cell lines (MKN-1, NUGC-4 and TMK-1) by ELISA, but its concentration in the sera of gastric cancer patients was almost same as that observed in the sera of the normal controls. In the gastric cancer tissues, C-ERC/mesothelin expression was associated with lymphatic invasion. N-ERC/mesothelin was secreted into the supernatants of gastric cancer cell lines, but does not appear to be a useful serum marker of gastric cancer.

Survival Benefit of Adjuvant Radiation Therapy for Gastric Cancer following Gastrectomy and Extended Lymphadenectomy

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R. A. Snyder

2012-01-01

Full Text Available Purpose. Although randomized trials suggest a survival benefit of adjuvant chemotherapy and radiation therapy (XRT for gastric adenocarcinoma, its use in patients who undergo an extended lymphadenectomy is less clear. The purpose of this study was to determine if a survival benefit exists in gastric cancer patients who receive adjuvant XRT following resection with extended lymphadenectomy. Methods. The SEER registry was queried for records of patients with resected gastric adenocarcinoma from 1988 to 2007. Multivariable Cox regression models were used to assess independent prognostic factors affecting overall survival (OS and disease-specific survival (DSS. Results. Of 15,060 patients identified, 3,208 (21% received adjuvant XRT. Adjuvant XRT was independently associated with improved OS (HR 0.67, CI 0.64–0.71 and DSS (HR 0.69, CI 0.65–0.73 in stages IB through IV (M0. This OS and DSS benefit persisted regardless of the extent of lymphadenectomy. Furthermore, lymphadenectomy with >25 LN resected was associated with improved OS and DSS compared with 25 LNs results in improved OS and DSS compared with patients who have fewer LNs resected.

Radiolysis of human gastric glycopolypeptides in aqueous solution

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Nagrani, S.; Bisby, R.H.

1986-01-01

The degradation of human gastric glycopolypeptides by hydroxyl radicals formed in irradiated N 2 0-saturated aqueous solution has been investigated. Gel exclusion chromatography shows the formation of lower molecular weight degradation products after irradiation and the appearance of unsaturated carbonyl-containing products which absorb in the ultra-violet. The radiation-induced destruction of individual monosaccharides in three human glycopolypeptides having different oligosaccharide chains has been measured. The results indicate that the structure of the oligosaccharide chain determines the extent of destruction of each type of monosaccharide present. (author)

Molecular classification of gastric cancer: a new paradigm.

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Shah, Manish A; Khanin, Raya; Tang, Laura; Janjigian, Yelena Y; Klimstra, David S; Gerdes, Hans; Kelsen, David P

2011-05-01

Gastric cancer may be subdivided into 3 distinct subtypes--proximal, diffuse, and distal gastric cancer--based on histopathologic and anatomic criteria. Each subtype is associated with unique epidemiology. Our aim is to test the hypothesis that these distinct gastric cancer subtypes may also be distinguished by gene expression analysis. Patients with localized gastric adenocarcinoma being screened for a phase II preoperative clinical trial (National Cancer Institute, NCI #5917) underwent endoscopic biopsy for fresh tumor procurement. Four to 6 targeted biopsies of the primary tumor were obtained. Macrodissection was carried out to ensure more than 80% carcinoma in the sample. HG-U133A GeneChip (Affymetrix) was used for cDNA expression analysis, and all arrays were processed and analyzed using the Bioconductor R-package. Between November 2003 and January 2006, 57 patients were screened to identify 36 patients with localized gastric cancer who had adequate RNA for expression analysis. Using supervised analysis, we built a classifier to distinguish the 3 gastric cancer subtypes, successfully classifying each into tightly grouped clusters. Leave-one-out cross-validation error was 0.14, suggesting that more than 85% of samples were classified correctly. Gene set analysis with the false discovery rate set at 0.25 identified several pathways that were differentially regulated when comparing each gastric cancer subtype to adjacent normal stomach. Subtypes of gastric cancer that have epidemiologic and histologic distinctions are also distinguished by gene expression data. These preliminary data suggest a new classification of gastric cancer with implications for improving our understanding of disease biology and identification of unique molecular drivers for each gastric cancer subtype. ©2011 AACR.

p75 Neurotrophin Receptor Suppresses the Proliferation of Human Gastric Cancer Cells

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Haifeng Jin

2007-06-01

Full Text Available Identifying an effective therapeutic target is pivotal in the treatment of gastric cancer. In this study, we investigated the expression of p75 neurotrophin receptor (p75NTR in gastric cancer and the impact of its alteration on tumor growth. p75NTR expression was absent or significantly decreased in 212 cases of gastric cancers compared with the normal gastric mucosa (P < .05. Moreover, p75NTR expression was also lost or significantly decreased in various human gastric cancer cell lines. p75NTR inhibited in vitro growth activities and caused dramatic attenuation of tumor growth in animal models by induction of cell cycle arrest. Upregulation of p75NTR led to downregulation of cyclin A, cyclin D1, cyclin E, cyclin-dependent kinase 2, p-Rb, and PCNA, but to upregulation of Rb and p27 expressions. Conversely, downregulating p75NTR with specific siRNA yielded inverse results. The rescue of tumor cells from cell cycle progression by a death domain-deleted dominant-negative antagonist of p75NTR (Δp75NTR showed that the death domain transduced antiproliferative activity in a ligandindependent manner and further demonstrated the inhibitive effect of p75NTR on growth in gastric cancer. Therefore, we provided evidence that p75NTR was a potential tumor suppressor and may be used as a therapeutic target for gastric cancer.

Effects of propranolol in combination with radiation on apoptosis and survival of gastric cancer cells in vitro

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Liao, Xinhua; Che, Xiangming; Zhao, Wei; Zhang, Danjie; Long, Houlong; Chaudhary, Prakash; Li, Haijun

2010-01-01

The National Comprehensive Cancer Network (NCCN) guidelines recommend radiotherapy as a standard treatment for patients with a high risk of recurrence in gastric cancer. Because gastric cancer demonstrates limited sensitivity to radiotherapy, a radiosensitizer might therefore be useful to enhance the radiosensitivity of patients with advanced gastric carcinoma. In this study, we evaluated if propranolol, a β-adrenoceptor (β-AR) antagonist, could enhance radiosensitivity and explored its precise molecular mechanism in gastric cancer cells. Human gastric adenocarcinoma cell lines (SGC-7901 and BGC-823) were treated with or without propranolol and exposed to radiation. Cell viability and clonogenic survival assays were performed, and cell apoptosis was evaluated with flow cytometry. In addition, the expression of nuclear factor κB (NF-κB), vascular endothelial growth factor (VEGF), cyclooxygenase 2 (COX-2), and epidermal growth factor receptor (EGFR) were detected by western blot and real-time reverse transcription polymerase chain reaction (PCR). Propranolol combined with radiation decreased cell viability and clonogenic survivability. Furthermore, it also induced apoptosis in both cell lines tested, as determined by Annexin V staining. In addition, treatment with propranolol decreased the level of NF-κB and, subsequently, down-regulated VEGF, COX-2, and EGFR expression. Taken together, these results suggested that propranolol enhanced the sensitivity of gastric cancer cells to radiation through the inhibition of β-ARs and the downstream NF-κB-VEGF/EGFR/COX-2 pathway

Definitive proton beam radiation therapy for inoperable gastric cancer

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Shibuya, Susumu; Takase, Yasuhiro; Aoyagi, Hiroyuki; Orii, Kazuo; Sharma, N.; Iwasaki, Yoji; Tsujii, Hirohiko; Tsujii, Hiroshi.

1991-01-01

Proton beam radiation therapy using 250 MeV protons was carried out on two patients with early gastric cancer (T1, N0, M0). One patient was an 85-year-old man with early gastric cancer of type IIa + IIc. The other one was a 70-year-old man with early gastric cancer of type IIc. In both cases histological examination of biopsy specimens showed differential adenocarcinoma; distant metastasis was not found by other examinations. Both patients were considered inoperable due to their poor cardiac and/or respiratory functions. Therefore, it was decided to treat them by definitive proton irradiation, delivering total doses of 86 Gy and 83 Gy, respectively. In both patients, skin erythema that did not require any special treatment was found in the irradiation field. Hematobiological examinations did not show any abnormality. Although endoscopic examination at two years after irradiation in the former case and at seven months in the latter case showed persistent gastric ulcer at the site of the cancerous lesions, cancer cells were not found histologically. Therefore, we concluded that proton irradiation therapy was useful for inoperable early gastric cancers. (author)

Western Validation of a Novel Gastric Cancer Prognosis Prediction Model in US Gastric Cancer Patients.

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Woo, Yanghee; Goldner, Bryan; Son, Taeil; Song, Kijun; Noh, Sung Hoon; Fong, Yuman; Hyung, Woo Jin

2018-03-01

A novel prediction model for accurate determination of 5-year overall survival of gastric cancer patients was developed by an international collaborative group (G6+). This prediction model was created using a single institution's database of 11,851 Korean patients and included readily available and clinically relevant factors. Already validated using external East Asian cohorts, its applicability in the American population was yet to be determined. Using the Surveillance, Epidemiology, and End Results (SEER) dataset, 2014 release, all patients diagnosed with gastric adenocarcinoma who underwent surgical resection between 2002 and 2012, were selected. Characteristics for analysis included: age, sex, depth of tumor invasion, number of positive lymph nodes, total lymph nodes retrieved, presence of distant metastasis, extent of resection, and histology. Concordance index (C-statistic) was assessed using the novel prediction model and compared with the prognostic index, the seventh edition of the TNM staging system. Of the 26,019 gastric cancer patients identified from the SEER database, 15,483 had complete datasets. Validation of the novel prediction tool revealed a C-statistic of 0.762 (95% CI 0.754 to 0.769) compared with the seventh TNM staging model, C-statistic 0.683 (95% CI 0.677 to 0.689), (p prediction model for gastric cancer in the American patient population. Its superior prediction of the 5-year survival of gastric cancer patients in a large Western cohort strongly supports its global applicability. Importantly, this model allows for accurate prognosis for an increasing number of gastric cancer patients worldwide, including those who received inadequate lymphadenectomy or underwent a noncurative resection. Copyright © 2017 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

Fisetin inhibits cellular proliferation and induces mitochondria-dependent apoptosis in human gastric cancer cells.

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Sabarwal, Akash; Agarwal, Rajesh; Singh, Rana P

2017-02-01

The anticancer effects of fisetin, a dietary agent, are largely unknown against human gastric cancer. Herein, we investigated the mechanisms of fisetin-induced inhibition of growth and survival of human gastric carcinoma AGS and SNU-1 cells. Fisetin (25-100 μM) caused significant decrease in the levels of G1 phase cyclins and CDKs, and increased the levels of p53 and its S15 phosphorylation in gastric cancer cells. We also observed that growth suppression and death of non-neoplastic human intestinal FHs74int cells were minimally affected by fisetin. Fisetin strongly increased apoptotic cells and showed mitochondrial membrane depolarization in gastric cancer cells. DNA damage was observed as early as 3 h after fisetin treatment which was accompanied with gamma-H2A.X(S139) phosphorylation and cleavage of PARP. Fisetin-induced apoptosis was observed to be independent of p53. DCFDA and MitoSOX analyses showed an increase in mitochondrial ROS generation in time- and dose-dependent fashion. It also increased cellular nitrite and superoxide generation. Pre-treatment with N-acetyl cysteine (NAC) inhibited ROS generation and also caused protection from fisetin-induced DNA damage. The formation of comets were observed in only fisetin treated cells which was blocked by NAC pre-treatment. Further investigation of the source of ROS, using mitochondrial respiratory chain (MRC) complex inhibitors, suggested that fisetin caused ROS generation specifically through complex I. Collectively, these results for the first time demonstrated that fisetin possesses anticancer potential through ROS production most likely via MRC complex I leading to apoptosis in human gastric carcinoma cells. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Toxicity and survival results of a phase II study investigating the role of postoperative chemoradioimmunotherapy for gastric adenocarcinoma

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Bese, N.S.; Yildirim, A.; Oeber, A. [Dept. of Radiation Oncology, Istanbul Univ., Cerrahpasa Medical School, Istanbul (Turkey); Bueyuekuenal, E.; Oezgueroglu, M.; Demir, G.; Mandel, N.M.; Demirelli, F.; Serdengecti, S. [Dept. of Internal Medicine, Medical Oncology Section, Istanbul Univ., Cerrahpasa Medical School, Istanbul (Turkey)

2005-10-01

Background and purpose: to investigate the role of postoperative concomitant chemoradioimmunotherapy in gastric adenocarcinoma patients. Patients and methods: 59 pateints, who underwent total or subtotal gastrectomy, with lymph node involvement, positive microscopic surgical margins or serosal involvement were included in the study. Radiotherapy started concomitantly with chemotherapy and levamisole. Extended-field radiotherapy was given to gastric bed and regional lymphatics via two anterior-posterior/posterior-anterior fields. A total dose of 45 Gy in 25 fractions with a fraction size of 1.8 Gy was planned. In 28 patients (48%) with positive surgical margins a 10-Gy boost dose was given to the anastomosis site. An adjuvant i.v. bolus of 450 mg/m{sup 2}/day 5-fluorouracil (5-FU) was administered concomitantly during the first 3 days and at the 20th day of irradiation. After completion of radiotherapy, i.v. boluses of 450 mg/m{sup 2}/day 5-FU and 25 mg/m{sup 2}/day rescuvorin were continued for 6 months once a week. Levamisole 40 mg/day orally was started at the 1st day of radiotherapy and also continued for 6 months. Median follow-up was 37 months (7-112 months). Results: median survival was 23 months. Overall 3- and 5-year survival rates amounted to 35% and 14%, respectively. Median survival of the patients with positive surgical margins was 22 months. The 3- and 5-year locoregional control rates were 59% and 55%, respectively. The most common toxicity was upper gastrointestinal system toxicity, which was observed in 42 patients (71%). Four patients (7%) died on account of early toxic effects, and six (10%) could not complete treatment. Conclusion: although 48% of the study population involved patients with microscopic residual disease, the survival results as a whole were satisfactory. However, due to high toxicity, radiotherapy must be delivered with the most proper techniques along with adequate nutrition and supportive care. (orig.)

CD147 expression in human gastric cancer is associated with tumor recurrence and prognosis.

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Dake Chu

Full Text Available CD147 is correlated with tumor aggressiveness in various human malignancies. Here, we investigated CD147 protein expression in 223 patients with gastric cancer by immunohistochemistry and analyzed its association with disease-free and overall survival. CD147 was increased in gastric cancer compared to normal tissues. Additionally, CD147 expression was associated with gastric cancer invasion, metastasis and TNM stage, whereas it was not related to age, sex, differentiation status, tumor site or Lauren classification. Kaplan-Meier analysis confirmed that CD147 was associated with disease-free and overall survival in patients with gastric cancer; i.e., patients with positive CD147 staining tend to have worse disease-free and overall survival. Moreover, Cox's proportional hazards analysis demonstrated that CD147 was an independent marker of disease-free and overall survival for patients with gastric cancer. These results confirm the association of CD147 with gastric cancer invasion and metastasis and prove that CD147 might be an indicator of tumor recurrence and prognosis in gastric cancer.

Nuclear factor-kappaB activation correlates with better prognosis and Akt activation in human gastric cancer.

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Lee, Byung Lan; Lee, Hye Seung; Jung, Jieun; Cho, Sung Jin; Chung, Hee-Yong; Kim, Woo Ho; Jin, Young-Woo; Kim, Chong Soon; Nam, Seon Young

2005-04-01

Because the biological significance of constitutive nuclear factor-kappaB (NF-kappaB) activation in human gastric cancer is unclear, we undertook this study to clarify the regulatory mechanism of NF-kappaB activation and its clinical significance. Immunohistochemistry for NF-kappaB/RelA was done on 290 human gastric carcinoma specimens placed on tissue array slides. The correlations between NF-kappaB activation and clinicopathologic features, prognosis, Akt activation, tumor suppressor gene expression, or Bcl-2 expression were analyzed. We also did luciferase reporter assay, Western blot analysis, and reverse transcription-PCR using the SNU-216 human gastric cancer cell line transduced with retroviral vectors containing constitutively active Akt or the NF-kappaB repressor mutant of IkappaBalpha. Nuclear expression of RelA was found in 18% of the gastric carcinomas and was higher in early-stage pathologic tumor-node-metastasis (P = 0.019). A negative correlation was observed between NF-kappaB activation and lymphatic invasion (P = 0.034) and a positive correlation between NF-kappaB activation and overall survival rate of gastric cancer patients (P = 0.0228). In addition, NF-kappaB activation was positively correlated with pAkt (P = 0.047), p16 (P = 0.004), adenomatous polyposis coli (P Smad4 (P = 0.002), and kangai 1 (P Akt. NF-kappaB activation was frequently observed in early-stage gastric carcinoma and was significantly correlated with better prognosis and Akt activation. These findings suggest that NF-kappaB activation is a valuable prognostic variable in gastric carcinoma.

Apoptosis induced by GanoPoly in human gastric cancer cell line ...

African Journals Online (AJOL)

use

2011-12-12

Dec 12, 2011 ... ... cancer's active therapy. Key words: Apoptosis, polysaccharide, human gastric cancer cells. ... The active components of polysaccharides are all glucans, which have a ... for the treatment of alleviated fatigue, night sweating,.

Combination of cisplatin/S-1 in the treatment of patients with advanced gastric or gastroesophageal adenocarcinoma: Results of noninferiority and safety analyses compared with cisplatin/5-fluorouracil in the First-Line Advanced Gastric Cancer Study.

Science.gov (United States)

Ajani, J A; Buyse, M; Lichinitser, M; Gorbunova, V; Bodoky, G; Douillard, J Y; Cascinu, S; Heinemann, V; Zaucha, R; Carrato, A; Ferry, D; Moiseyenko, V

2013-11-01

The aim of developing oral fluorouracil (5-FU) is to provide a more convenient administration route with similar efficacy and the best achievable tolerance. S-1, a novel oral fluoropyrimidine, was specifically designed to overcome the limitations of intravenous fluoropyrimidine therapies. A multicentre, randomised phase 3 trial was undertaken to compare S-1/cisplatin (CS) with infusional 5-FU/cisplatin (CF) in 1053 patients with untreated, advanced gastric/gastroesophageal adenocarcinoma. This report discusses a post-hoc noninferiority overall survival (OS) and safety analyses. Results (1029 treated; CS = 521/CF = 508) revealed OS in CS (8.6 months) was statistically noninferior to CF (7.9 months) [hazard ratio (HR) = 0.92 (two-sided 95% confidence interval (CI), 0.80-1.05)] for any margin equal to or greater than 1.05. Statistically significant safety advantages for the CS arm were observed [G3/4 neutropenia (CS, 18.6%; CF, 40.0%), febrile neutropenia (CS, 1.7%; CF, 6.9%), G3/4 stomatitis (CS, 1.3%; CF, 13.6%), diarrhoea (all grades: CS, 29.2%; CF, 38.4%) and renal adverse events (all grades: CS, 18.8%; CF, 33.5%)]. Hand-foot syndrome, infrequently reported, was mainly grade 1/2 in both arms. Treatment-related deaths were significantly lower in the CS arm than the CF arm (2.5% and 4.9%, respectively; Psafety profile and provides a new treatment option for patients with advanced gastric carcinoma. Copyright © 2013 Elsevier Ltd. All rights reserved.

BAK overexpression mediates p53-independent apoptosis inducing effects on human gastric cancer cells

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Liu Jun

2004-07-01

Full Text Available Abstract Background BAK (Bcl-2 homologous antagonist/killer is a novel pro-apoptotic gene of the Bcl-2 family. It has been reported that gastric tumors have reduced BAK levels when compared with the normal mucosa. Moreover, mutations of the BAK gene have been identified in human gastrointestinal cancers, suggesting that a perturbation of BAK-mediated apoptosis may contribute to the pathogenesis of gastric cancer. In this study, we explored the therapeutic effects of gene transfer mediated elevations in BAK expression on human gastric cancer cells in vitro. Methods Eukaryotic expression vector for the BAK gene was constructed and transferred into gastric cancer cell lines, MKN-45 (wild-type p53 and MKN-28 (mutant-type p53. RT-PCR and Western Blotting detected cellular BAK gene expression. Cell growth activities were detected by MTT colorimetry and flow cytometry, while apoptosis was assayed by electronic microscopy and TUNEL. Western Blotting and colorimetry investigated cellular caspase-3 activities. Results BAK gene transfer could result in significant BAK overexpression, decreased in vitro growth, cell cycle G0/G1 arrest, and induced apoptosis in gastric cancer cells. In transferred cells, inactive caspase-3 precursor was cleaved into the active subunits p20 and p17, during BAK overexpression-induced apoptosis. In addition, this process occurred equally well in p53 wild-type (MKN-45, or in p53 mutant-type (MKN-28 gastric cancer cells. Conclusions The data presented suggests that overexpression of the BAK gene can lead to apoptosis of gastric cancer cells in vitro, which does not appear to be dependent on p53 status. The action mechanism of BAK mediated apoptosis correlates with activation of caspase-3. This could be served as a potential strategy for further development of gastric cancer therapies.

BAK overexpression mediates p53-independent apoptosis inducing effects on human gastric cancer cells

International Nuclear Information System (INIS)

Tong, Qiang-Song; Zheng, Li-Duan; Wang, Liang; Liu, Jun; Qian, Wei

2004-01-01

BAK (Bcl-2 homologous antagonist/killer) is a novel pro-apoptotic gene of the Bcl-2 family. It has been reported that gastric tumors have reduced BAK levels when compared with the normal mucosa. Moreover, mutations of the BAK gene have been identified in human gastrointestinal cancers, suggesting that a perturbation of BAK-mediated apoptosis may contribute to the pathogenesis of gastric cancer. In this study, we explored the therapeutic effects of gene transfer mediated elevations in BAK expression on human gastric cancer cells in vitro. Eukaryotic expression vector for the BAK gene was constructed and transferred into gastric cancer cell lines, MKN-45 (wild-type p53) and MKN-28 (mutant-type p53). RT-PCR and Western Blotting detected cellular BAK gene expression. Cell growth activities were detected by MTT colorimetry and flow cytometry, while apoptosis was assayed by electronic microscopy and TUNEL. Western Blotting and colorimetry investigated cellular caspase-3 activities. BAK gene transfer could result in significant BAK overexpression, decreased in vitro growth, cell cycle G 0 /G 1 arrest, and induced apoptosis in gastric cancer cells. In transferred cells, inactive caspase-3 precursor was cleaved into the active subunits p20 and p17, during BAK overexpression-induced apoptosis. In addition, this process occurred equally well in p53 wild-type (MKN-45), or in p53 mutant-type (MKN-28) gastric cancer cells. The data presented suggests that overexpression of the BAK gene can lead to apoptosis of gastric cancer cells in vitro, which does not appear to be dependent on p53 status. The action mechanism of BAK mediated apoptosis correlates with activation of caspase-3. This could be served as a potential strategy for further development of gastric cancer therapies

Opioid-induced delay in gastric emptying: a peripheral mechanism in humans.

LENUS (Irish Health Repository)

Murphy, D B

2012-02-03

BACKGROUND: Opioids delay gastric emptying, which in turn may increase the risk of vomiting and pulmonary aspiration. Naloxone reverses this opiate action on gastric emptying, but it is not known whether this effect in humans is mediated by central or peripheral opiate antagonism. The importance of peripheral opioid receptor antagonism in modulating opioid-induced delay in gastric emptying was evaluated using methylnaltrexone, a quaternary derivative of the opiate antagonist naltrexone, which does not cross the blood-brain barrier. METHODS: In a randomized, double-blind, crossover placebo-controlled study, 11 healthy volunteers were given either placebo (saline), 0.09 mg\\/kg morphine, or 0.09 mg\\/kg morphine plus 0.3 mg\\/kg methylnaltrexone on three separate occasions before ingesting 500 ml deionized water. The rate of gastric emptying was measured by two methods: a noninvasive epigastric bioimpedance technique and the acetaminophen absorption test. RESULTS: The epigastric bioimpedance technique was sufficiently sensitive to detect opioid-induced changes in the rate of gastric emptying. The mean +\\/- SD time taken for the gastric volume to decrease to 50% (t0.5) after placebo was 5.5 +\\/- 2.1 min. Morphine prolonged gastric emptying to (t0.5) of 21 +\\/- 9.0 min (P < 0.03). Methylnaltrexone given concomitantly with morphine reversed the morphine-induced delay in gastric emptying to a t0.5 of 7.4 +\\/- 3.0 (P < 0.04). Maximum concentrations and area under the concentration curve from 0 to 90 min of serum acetaminophen concentrations after morphine were significantly different from placebo and morphine administered concomitantly with methylnaltrexone (P < 0.05). No difference in maximum concentration or area under the concentration curve from 0 to 90 min was noted between placebo and methylnaltrexone coadministered with morphine. CONCLUSIONS: The attenuation of morphine-induced delay in gastric emptying by methylnaltrexone suggests that the opioid effect is

/sup 99m/Tc-labeled solid-phase meal: a quantitative clinical measurement of human gastric emptying

Energy Technology Data Exchange (ETDEWEB)

Martin, J.L.; Beck, W.J.; McDonald, A.P.; Carlson, G.M.; Mathias, J.R.

1983-08-01

A solid-phase meal labeled with /sup 99m/Tc-sulfur colloid provides an improved clinical test for the quantitative evaluation of human gastric emptying. We studied 12 healthy male controls and five male patients with known gastric stasis secondary to a vagotomy and drainage procedure. All subjects were fasted for 8 hours before the study, and each consumed an unbuttered biscuit and a poached egg white containing 1 mCi of /sup 99m/Tc-sulfur colloid. For 2 hours, 60-second counts were measured every 10 minutes by a Pho Gamma III scintillation camera. The t/sup 1///sup 2/ for control subjects was 60 minutes, at which time patients with gastric stasis had retained 98% of the test meal. At 120 minutes, control subjects and patients with gastric stasis had 4.7% and 89%, respectively, of the meal remaining in the stomach. The solid-phase test meal labeled with /sup 99m/Tc-sulfur colloid is easy to perform and can be used clinically to quantitatively measure gastric emptying in humans. This test can discriminate between control subjects and patients with known gastric stasis.

/sup 99m/Tc-labeled solid-phase meal: a quantitative clinical measurement of human gastric emptying

International Nuclear Information System (INIS)

Martin, J.L.; Beck, W.J.; McDonald, A.P.; Carlson, G.M.; Mathias, J.R.

1983-01-01

A solid-phase meal labeled with /sup 99m/Tc-sulfur colloid provides an improved clinical test for the quantitative evaluation of human gastric emptying. We studied 12 healthy male controls and five male patients with known gastric stasis secondary to a vagotomy and drainage procedure. All subjects were fasted for 8 hours before the study, and each consumed an unbuttered biscuit and a poached egg white containing 1 mCi of /sup 99m/Tc-sulfur colloid. For 2 hours, 60-second counts were measured every 10 minutes by a Pho Gamma III scintillation camera. The t 1 / 2 for control subjects was 60 minutes, at which time patients with gastric stasis had retained 98% of the test meal. At 120 minutes, control subjects and patients with gastric stasis had 4.7% and 89%, respectively, of the meal remaining in the stomach. The solid-phase test meal labeled with /sup 99m/Tc-sulfur colloid is easy to perform and can be used clinically to quantitatively measure gastric emptying in humans. This test can discriminate between control subjects and patients with known gastric stasis

Establishment and conventional cytogenetic characterization of three gastric cancer cell lines.

Science.gov (United States)

Leal, Mariana Ferreira; Martins do Nascimento, José Luiz; da Silva, Carla Elvira Araújo; Vita Lamarão, Maria Fernanda; Calcagno, Danielle Queiroz; Khayat, André Salim; Assumpção, Paulo Pimentel; Cabral, Isabel Rosa; de Arruda Cardoso Smith, Marília; Burbano, Rommel Rodríguez

2009-11-01

Gastric cancer is the fourth most frequent type of cancer and the second most frequent cause of cancer mortality worldwide. Only a modest number of gastric carcinoma cell lines have been isolated thus far. Here we describe the establishment and cytogenetic characterization of three new gastric cancer cell lines obtained from primary gastric adenocarcinoma (ACP02 and ACP03) and cancerous ascitic fluid (AGP01) of individuals from northern Brazil. ACP02, ACP03, and AGP01 cell lines are presently in the 60th passage. The cell lines grew in a disorganized single layer with some agglomerations and heterogeneous divisions (bipolar and multipolar). All cell lines exhibited a composite karyotype with several clonal chromosome alterations. Trisomy 8 was the most frequent alteration. Chromosome 8 aneusomy was confirmed by fluorescence in situ hybridization. All cell lines also exhibited trisomy 7 and deletion of chromosome arm 17p. These results suggest that, although frequent chromosome alterations are commonly observed due to culture process, the ACP02, ACP03, and AGP01 cell lines and primary gastric cancer from individuals of northern Brazil share genetic alterations, supporting use of these cell lines as a model of gastric carcinogenesis in this population.

Urokinase plasminogen activator receptor on invasive cancer cells: A prognostic factor in distal gastric adenocarcinoma

DEFF Research Database (Denmark)

Alpizar, Warner Enrique Alpizar; Christensen, Ib Jarle; Santoni-Rugiu, Eric

2012-01-01

Gastric cancer is the second cancer causing death worldwide. The five-year survival for this malignancy is below 25% and few parameters have shown an impact on the prognosis of the disease. The receptor for urokinase plasminogen activator (uPAR) is involved in extracellular matrix degradation...... by mediating cell surface associated plasminogen activation, and its presence on gastric cancer cells is linked to micrometastasis and poor prognosis. Using immunohistochemistry, the prognostic significance of uPAR was evaluated in tissue samples from a retrospective series of 95 gastric cancer patients. u...... association between the expression of uPAR on tumor cells in the peripheral invasion zone and overall survival of gastric cancer patients (HR = 2.16; 95% CI: 1.13-4.14; p = 0.02). Multivariate analysis showed that uPAR immunoreactivity in cancer cells at the invasive front is an independent prognostic factor...

The Invasion and Metastasis Promotion Role of CD97 Small Isoform in Gastric Carcinoma

DEFF Research Database (Denmark)

Liu, Daren; Trojanowicz, Bogusz; Ye, Longyun

2012-01-01

CD97 is over-expressed in the majority of gastric adenocarcinomas and is associated with its dedifferentiation and aggressiveness. Our previous results demonstrated that out of three CD97 isoforms tested, only the small one was able to promote increased invasiveness in vitro. Based on these data ...

Total, caffeinated and decaffeinated coffee and tea intake and gastric cancer risk

DEFF Research Database (Denmark)

Sanikini, Harinakshi; Dik, Vincent K; Siersema, Peter D

2015-01-01

Prospective studies examining the association between coffee and tea consumption and gastric cancer risk have shown inconsistent results. We investigated the association between coffee (total, caffeinated and decaffeinated) and tea consumption and the risk of gastric cancer by anatomical site...... and histological type in the EPIC study. Coffee and tea consumption was assessed by dietary questionnaires at baseline. Adjusted hazard ratios (HRs) were calculated using Cox regression models. During 11.6 years of follow up, 683 gastric adenocarcinoma cases were identified among 477,312 participants. We found......) and tea (HR 0.81, 95%-CI: 0.59-1.09; quartile 4 vs. non/quartile 1). When stratified by anatomical site, we observed a significant positive association between gastric cardia cancer risk and total coffee consumption per increment of 100mL/day (HR 1.06, 95%-CI: 1.03-1.11). Similarly, a significant positive...

Experimental gastric carcinogenesis in Cebus apella nonhuman primates.

Directory of Open Access Journals (Sweden)

Joana de Fátima Ferreira Borges da Costa

Full Text Available The evolution of gastric carcinogenesis remains largely unknown. We established two gastric carcinogenesis models in New-World nonhuman primates. In the first model, ACP03 gastric cancer cell line was inoculated in 18 animals. In the second model, we treated 6 animals with N-methyl-nitrosourea (MNU. Animals with gastric cancer were also treated with Canova immunomodulator. Clinical, hematologic, and biochemical, including C-reactive protein, folic acid, and homocysteine, analyses were performed in this study. MYC expression and copy number was also evaluated. We observed that all animals inoculated with ACP03 developed gastric cancer on the 9(th day though on the 14(th day presented total tumor remission. In the second model, all animals developed pre-neoplastic lesions and five died of drug intoxication before the development of cancer. The last surviving MNU-treated animal developed intestinal-type gastric adenocarcinoma observed by endoscopy on the 940(th day. The level of C-reactive protein level and homocysteine concentration increased while the level of folic acid decreased with the presence of tumors in ACP03-inoculated animals and MNU treatment. ACP03 inoculation also led to anemia and leukocytosis. The hematologic and biochemical results corroborate those observed in patients with gastric cancer, supporting that our in vivo models are potentially useful to study this neoplasia. In cell line inoculated animals, we detected MYC immunoreactivity, mRNA overexpression, and amplification, as previously observed in vitro. In MNU-treated animals, mRNA expression and MYC copy number increased during the sequential steps of intestinal-type gastric carcinogenesis and immunoreactivity was only observed in intestinal metaplasia and gastric cancer. Thus, MYC deregulation supports the gastric carcinogenesis process. Canova immunomodulator restored several hematologic measurements and therefore, can be applied during/after chemotherapy to increase the

Gastric leiomyosarcoma about seven cases

International Nuclear Information System (INIS)

Gonzalez, D.; Vicente, J.; Antunez, C.; Telechea, M.; Ayala, D.; Torres, M.; Di Leoni, F.

2004-01-01

Gastric leiomyosarcoma is a rare tumor. Its clinical symptoms are non specific, its diagnosis during preoperative is generaly difficult. Surgery is the main therapeutic pillar because neither radiation nor chemical therapy have proven to be effective.Even though its prognosis taken globally is more favorable than of adenocarcinoma, its biologic behavior is hi gly and depends on various factors. In this paper the author conduct a retrospective analysis of seven cases of gastric leiomyosarcoma s treated in health care centers throughout Uruguay, not only in Montevideo but in other towns as well, during the period extending as from 1992 through 2001. In no case was diagnosis made in the pre or intra operative; in 43% of cases there occurred tumor involvement of the surgical resection margins. Local resections were the most frequent procedures employed, there being no operative mortality, survivals being 5 and 9 years and in 2 others survival extended to 10 years.The three remaining ones have not as yet completed the first year

Synchrotron-radiation phase-contrast imaging of human stomach and gastric cancer: in vitro studies.

Science.gov (United States)

Tang, Lei; Li, Gang; Sun, Ying-Shi; Li, Jie; Zhang, Xiao-Peng

2012-05-01

The electron density resolution of synchrotron-radiation phase-contrast imaging (SR-PCI) is 1000 times higher than that of conventional X-ray absorption imaging in light elements, through which high-resolution X-ray imaging of biological soft tissue can be achieved. For biological soft tissue, SR-PCI can give better imaging contrast than conventional X-ray absorption imaging. In this study, human resected stomach and gastric cancer were investigated using in-line holography and diffraction enhanced imaging at beamline 4W1A of the Beijing Synchrotron Radiation Facility. It was possible to depict gastric pits, measuring 50-70 µm, gastric grooves and tiny blood vessels in the submucosa layer by SR-PCI. The fine structure of a cancerous ulcer was displayed clearly on imaging the mucosa. The delamination of the gastric wall and infiltration of cancer in the submucosa layer were also demonstrated on cross-sectional imaging. In conclusion, SR-PCI can demonstrate the subtle structures of stomach and gastric cancer that cannot be detected by conventional X-ray absorption imaging, which prompt the X-ray diagnosis of gastric disease to the level of the gastric pit, and has the potential to provide new methods for the imageology of gastric cancer.

Effects of the H(2)-receptor antagonist ranitidine on gastric motor function after a liquid meal in healthy humans

DEFF Research Database (Denmark)

Madsen, Jan Lysgård; Graff, J

2008-01-01

Objective. Studies on animals have shown that histamine may be involved in the regulation of gastrointestinal smooth muscle tone. However, the role of histamine in the regulation of human gastric motor function is not clear. This study examined the effect of ranitidine, an H(2)-receptor antagonist......, on gastric volume and gastric emptying after a liquid meal in healthy humans. Material and methods. Twelve healthy volunteers participated in a randomized crossover study with 50 mg ranitidine as a bolus intravenously versus no medication. Gastric volume at baseline was determined with single photon emission...... computed tomography (SPECT) after intravenous injection of 99(m)Tc-pertechnetate. After ingestion of a 600-mL liquid meal radiolabelled with (111)In-diethylenetriaminepentaacetic acid, dual-isotope technique with SPECT and planar imaging assessed gastric volume as well as gastric emptying. Results...

Effects of the H2-receptor antagonist ranitidine on gastric motor function after a liquid meal in healthy humans

DEFF Research Database (Denmark)

Madsen, J.L.; Graff, J.

2008-01-01

OBJECTIVE: Studies on animals have shown that histamine may be involved in the regulation of gastrointestinal smooth muscle tone. However, the role of histamine in the regulation of human gastric motor function is not clear. This study examined the effect of ranitidine, an H(2)-receptor antagonist......, on gastric volume and gastric emptying after a liquid meal in healthy humans. MATERIAL AND METHODS: Twelve healthy volunteers participated in a randomized crossover study with 50 mg ranitidine as a bolus intravenously versus no medication. Gastric volume at baseline was determined with single photon emission...... computed tomography (SPECT) after intravenous injection of 99(m)Tc-pertechnetate. After ingestion of a 600-mL liquid meal radiolabelled with (111)In-diethylenetriaminepentaacetic acid, dual-isotope technique with SPECT and planar imaging assessed gastric volume as well as gastric emptying. RESULTS...

Effect of sildenafil on gastric emptying and postprandial frequency of antral contractions in healthy humans

DEFF Research Database (Denmark)

Madsen, Jan Lysgård; Søndergaard, S B; Fuglsang, Stefan

2004-01-01

BACKGROUND: Sildenafil is known to block phosphodiesterase type 5, which degrades nitric oxide-stimulated cyclic guanosine monophosphate, thereby relaxing smooth muscle cells in various organs. The effect of sildenafil on gastric motor function after a meal was investigated in healthy humans...... gastric emptying and postprandial frequency of antral contractions. RESULTS: The area under the curve of gastric retention versus time of liquid or solid radiolabelled marker was not changed by sildenafil intake, nor was the postprandial frequency of antral contractions affected by sildenafil. CONCLUSION......: A single dose of 50 mg sildenafil does not change gastric emptying or postprandial frequency of antral contractions in healthy volunteers....

Increased numbers of Foxp3-positive regulatory T cells in gastritis, peptic ulcer and gastric adenocarcinoma

Science.gov (United States)

Cheng, Hsin-Hung; Tseng, Guan-Ying; Yang, Hsiao-Bai; Wang, Hung-Jung; Lin, Hwai-Jeng; Wang, Wen-Ching

2012-01-01

AIM: To determine the number of regulatory T cells (Tregs) in gastric mucosa of patients with gastritis, peptic ulcers and gastric cancer. METHODS: This study was a retrospective analysis of gastric antrum biopsy specimens from healthy controls (n = 22) and patients with gastritis (n = 30), peptic ulcer (n = 83), or gastric cancer (n = 32). Expression of CD4, CD25 and Foxp3 was determined by immunohistochemistry in three consecutive sections per sample. RESULTS: Compared with healthy controls, there was an increased number of CD25+ and Foxp3+ cells in patients with gastritis (P = 0.004 and P = 0.008), peptic ulcer (P gastritis (P gastritis and peptic ulcer groups. PMID:22228968

Adenocarcinoma mucoproductor de colon con infiltración de estómago y metástasis ováricas (tumor de Krukenberg Colon mucoproducing adenocarcinoma with stomach infiltration and ovarian metastases (Krukenberg's tumor

Directory of Open Access Journals (Sweden)

Orestes Noel Mederos Curbelo

2011-12-01

Full Text Available Se presenta una paciente femenina de 29 años, operada de urgencia por presentar un gran tumor que incluía cuerpo gástrico y colon trasverso, con una perforación gástrica. Se realizó una gastrectomía subtotal con colectomía trasversa en bloque que incluyó el epiplón mayor. El diagnóstico histológico fue adenocarcinoma túbulo papilar mucoproductor de origen colónico, que infiltra hasta la serosa y pared gástrica. Se realizó tratamiento adyuvante con poliquimioterapia. Diez meses después presenta un tumor en hipogastrio, que al tacto vaginal, correspondía a los órganos genitales, sospecha clínica que confirman el ultrasonido abdominal y la tomografía axial computarizada. El hallazgo transoperatorio fueron tumores voluminosos de ambos ovarios, y otro tumor que afectaba la unión rectosigmoide. Se realizó una histerectomía radical con ooforectomía bilateral y sigmoidectomía, se reseca la porción proximal del recto, y se cierra tipo Hartman. El diagnóstico histológico final fue metástasis en serosa uterina e intestinal, y en ambos ovarios de adenocarcinoma mucoproductor, túbulo papilar de intestino previamente diagnosticado (tumor de Krukenberg. Se complementó el tratamiento con poliquimioterapia adyuvante.This is the case of a woman aged 29 operated on of emergency due to a tumor involving gastric body and transverse colon with gastric perforation. A subtotal gastrectomy with block transverse colectomy including the greater omentum was carried out. The histological diagnosis was a mucoproducing papillary tubular adenocarcinoma of colonic origin infiltrating to serosa and gastric wall. An adjuvant treatment was applied with poly-chemotherapy. Ten months later appears a hypogastric tumor which at vaginal manual examination corresponding to genital organs, clinical suspicion confirmed by abdominal ultrasound and computerized axial tomography. The transoperative findings were bulky tumors of both ovaries and another tumor

Inflammation-Related Carcinogenesis and Prevention in Esophageal Adenocarcinoma Using Rat Duodenoesophageal Reflux Models

International Nuclear Information System (INIS)

Fujimura, Takashi; Oyama, Katsunobu; Sasaki, Shozo; Nishijima, Koji; Miyashita, Tomoharu; Ohta, Tetsuo; Koichi, Miwa; Takanori, Hattori

2011-01-01

Development from chronic inflammation to Barrett's adenocarcinoma is known as one of the inflammation-related carcinogenesis routes. Gastroesophageal reflux disease induces regurgitant esophagitis, and esophageal mucosa is usually regenerated by squamous epithelium, but sometimes and somewhere replaced with metaplastic columnar epithelium. Specialized columnar epithelium, so-called Barrett's epithelium (BE), is a risk factor for dysplasia and adenocarcinoma in esophagus. Several experiments using rodent model inducing duodenogastroesophageal reflux or duodenoesophageal reflux revealed that columnar epithelium, first emerging at the proliferative zone, progresses to dysplasia and finally adenocarcinoma, and exogenous carcinogen is not necessary for cancer development. It is demonstrated that duodenal juice rather than gastric juice is essential to develop esophageal adenocarcinoma in not only rodent experiments, but also clinical studies. Antireflux surgery and chemoprevention by proton pump inhibitors, nonsteroidal anti-inflammatory drugs, selective cyclooxygenase-2 inhibitors, green tea, retinoic acid and thioproline showed preventive effects on the development of Barrett's adenocarcinoma in rodent models, but it remains controversial whether antireflux surgery could regress BE and prevent esophageal cancer in clinical observation. The Chemoprevention for Barrett's Esophagus Trial (CBET), a phase IIb, multicenter, randomized, double-masked study using celecoxib in patients with Barrett's dysplasia failed to prove to prevent progression of dysplasia to cancer. The AspECT (Aspirin Esomeprazole Chemoprevention Trial), a large multicenter phase III randomized trial to evaluate the effects of esomeprazole and/or aspirin on the rate of progression to high-grade dysplasia or adenocarcinoma in patients with BE is now ongoing

Inflammation-Related Carcinogenesis and Prevention in Esophageal Adenocarcinoma Using Rat Duodenoesophageal Reflux Models

Energy Technology Data Exchange (ETDEWEB)

Fujimura, Takashi, E-mail: tphuji@staff.kanazawa-u.ac.jp; Oyama, Katsunobu; Sasaki, Shozo; Nishijima, Koji; Miyashita, Tomoharu; Ohta, Tetsuo [Gastroenterologic Surgery, Kanazawa University Hospital, Kanazawa, Japan, 13-1 Takaramachi, Kanazawa, Ishikawa 920-8641 (Japan); Koichi, Miwa [Houju Memorial Hospital, Nomi, Japan, 11-71 Midorigaoka, Nomi, Ishikawa 923-1226 (Japan); Takanori, Hattori [Division of Molecular and Diagnostic Pathology, Shiga University of Medical Science, Otsu, Japan, Seta Tsukinowa-cho, Otsu, Shiga 520-2192 (Japan)

2011-08-10

Development from chronic inflammation to Barrett's adenocarcinoma is known as one of the inflammation-related carcinogenesis routes. Gastroesophageal reflux disease induces regurgitant esophagitis, and esophageal mucosa is usually regenerated by squamous epithelium, but sometimes and somewhere replaced with metaplastic columnar epithelium. Specialized columnar epithelium, so-called Barrett's epithelium (BE), is a risk factor for dysplasia and adenocarcinoma in esophagus. Several experiments using rodent model inducing duodenogastroesophageal reflux or duodenoesophageal reflux revealed that columnar epithelium, first emerging at the proliferative zone, progresses to dysplasia and finally adenocarcinoma, and exogenous carcinogen is not necessary for cancer development. It is demonstrated that duodenal juice rather than gastric juice is essential to develop esophageal adenocarcinoma in not only rodent experiments, but also clinical studies. Antireflux surgery and chemoprevention by proton pump inhibitors, nonsteroidal anti-inflammatory drugs, selective cyclooxygenase-2 inhibitors, green tea, retinoic acid and thioproline showed preventive effects on the development of Barrett's adenocarcinoma in rodent models, but it remains controversial whether antireflux surgery could regress BE and prevent esophageal cancer in clinical observation. The Chemoprevention for Barrett's Esophagus Trial (CBET), a phase IIb, multicenter, randomized, double-masked study using celecoxib in patients with Barrett's dysplasia failed to prove to prevent progression of dysplasia to cancer. The AspECT (Aspirin Esomeprazole Chemoprevention Trial), a large multicenter phase III randomized trial to evaluate the effects of esomeprazole and/or aspirin on the rate of progression to high-grade dysplasia or adenocarcinoma in patients with BE is now ongoing.

Correlation of metastasis characteristics with prognosis in gastric mixed adenoneuroendocrine carcinoma: Two case reports.

Science.gov (United States)

Tang, Qiang; Zhou, Zili; Chen, Jinhuang; Di, Maojun; Ji, Jintong; Yuan, Wenzheng; Liu, Zhengyi; Wu, Liang; Zhang, Xudan; Li, Kang; Shu, Xiaogang

2017-12-01

This article is aimed to retrospect the clinicopathological data of 2 cases of gastric MANENCs. MANEC is a rare biphasic tumor type that is coexistence of dual neuroendocrine and adenocarcinoma differentiation with each composing exceeding 30% volume. Gastric MANEC have just been reported anecdotally in the literature due to their rarity and heterogeneity. According to our study, these neoplasms have 3 different metastasis patterns: only adenocarcinomatous or neuroendocrine carcinoma and both of the 2 components. We first focus on the correlation of metastasis characteristics with prognosis in gastric MANEC, which may be potential implications for the choice of chemotherapy. The 2 cases of patient shared several symptoms: epigastric discomfort, weight loss, hematemesis, or melena. The 2 patients were diagnosis as MANEC based on the identification of histopathological analysis. In case 1, the poor differentiated adenocarcinoma accounted for 30%, the neuroendocrine part account for 70% and both of the 2 components metastasized to the lymph nodes, whereas in case 2, poorly differentiated adenocarcinoma accounted for 70%, the neuroendocrine part for 30% and only the glandular component invaded regional lymph nodes. The first patient underwent laparoscopic radical gastrectomy and underwent adjuvant chemotherapy, combination of cisplatin, and etoposide successfully. The second patient received radical gastronomy, and did not receive any chemotherapy due to general weakness. The first patient is alive with no evidence of recurrence, and the second patient died 6 months after the operation. The assessment of metastatic sites should be a routine pathological practice, which is crucial for clinical decision-making and the selection of management. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

MCF-7 human mammary adenocarcinoma cells exhibit augmented responses to human insulin on a collagen IV surface

DEFF Research Database (Denmark)

Listov-Saabye, Nicolai; Jensen, Marianne Blirup; Kiehr, Benedicte

2009-01-01

Human mammary cell lines are extensively used for preclinical safety assessment of insulin analogs. However, it is essentially unknown how mitogenic responses can be optimized in mammary cell-based systems. We developed an insulin mitogenicity assay in MCF-7 human mammary adenocarcinoma cells......, under low serum (0.1% FCS) and phenol red-free conditions, with 3H thymidine incorporation as endpoint. Based on EC50 values determined from 10-fold dilution series, beta-estradiol was the most potent mitogen, followed by human IGF-1, human AspB10 insulin and native human insulin. AspB10 insulin...... was significantly more mitogenic than native insulin, validating the ability of the assay to identify hypermitogenic human insulin analogs. With MCF-7 cells on a collagen IV surface, the ranking of mitogens was maintained, but fold mitogenic responses and dynamic range and steepness of dose-response curves were...

Simultaneous Occurrence of Early Gastric Carcinoma and Mucosa-Associated Lymphoid Tissue Lymphoma of the Omentum

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Tomohiro Murakami

2014-03-01

Full Text Available The simultaneous association of gastric carcinoma with omental mucosa-associated lymphoid tissue (MALT lymphoma is a rare event that has not been reported previously. We focused on the hypothetic pathogenetic mechanisms, diagnosis and treatment of this rare condition. A 55-year-old woman with Helicobacter pylori infection underwent distal gastrectomy in our hospital. Three independent early gastric cancers and a mass near the cecum were diagnosed preoperatively. Pathological review of the resected stomach showed three independent early signet ring cell gastric carcinomas, and the mass in the omentum near the cecum was shown to be omental MALT lymphoma. Due to the nature of the patient's disease, she was started on medical eradication of H. pylori. Synchronous gastric adenocarcinoma and omental MALT lymphoma is a rare event. Special attention given to H. pylori-associated gastric cancer patients can avoid misdiagnosis and lead to adequate treatment.

EGFR, HER-2 and KRAS in canine gastric epithelial tumors: a potential human model?

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Rossella Terragni

Full Text Available Epidermal growth factor receptor (EGFR or HER-1 and its analog c-erbB-2 (HER-2 are protein tyrosine kinases correlated with prognosis and response to therapy in a variety of human cancers. KRAS mediates the transduction of signals between EGFR and the nucleus, and its mutation has been identified as a predictor of resistance to anti-EGFR drugs. In human oncology, the importance of the EGFR/HER-2/KRAS signalling pathway in gastric cancer is well established, and HER-2 testing is required before initiating therapy. Conversely, this pathway has never been investigated in canine gastric tumours. A total of 19 canine gastric epithelial neoplasms (5 adenomas and 14 carcinomas were retrospectively evaluated for EGFR/HER-2 immunohistochemical expression and KRAS mutational status. Five (35.7% carcinomas were classified as intestinal-type and 9 (64.3% as diffuse-type. EGFR was overexpressed (≥ 1+ in 8 (42.1% cases and HER-2 (3+ in 11 (57.9% cases, regardless of tumour location or biological behaviour. The percentage of EGFR-positive tumours was significantly higher in the intestinal-type (80% than in the diffuse-type (11.1%, p = 0.023. KRAS gene was wild type in 18 cases, whereas one mucinous carcinoma harboured a point mutation at codon 12 (G12R. EGFR and HER-2 may be promising prognostic and therapeutic targets in canine gastric epithelial neoplasms. The potential presence of KRAS mutation should be taken into account as a possible mechanism of drug resistance. Further studies are necessary to evaluate the role of dog as a model for human gastric cancer.

K-ras mutations in gastric stump carcinomas and in carcinomas from the non-operated stomach

NARCIS (Netherlands)

van Rees, B. P.; Musler, A.; Caspers, E.; Drillenburg, P.; Craanen, M. E.; Polkowski, W.; Chibowski, D.; Offerhaus, G. J.

1999-01-01

Partial gastrectomy is a well-established pre-malignant condition. It is postulated that in the gastric stump an accelerated neoplastic process takes place, similar to that of (intestinal type) adenocarcinoma from the non-operated stomach. K-ras codon 12 mutation is one of the most frequent

The effect of ω-fatty acids on the expression of phospholipase A2 group 2A in human gastric cancer patients.

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Shariati, Mahboube; Aghaei, Mahmoud; Movahedian, Ahmad; Somi, Mohammad Hosein; Dolatkhah, Homayun; Aghazade, Ahmad Mirza

2016-01-01

Studies show that polyunsaturated fatty acids (PUFAs) may have an inhibitory role in carcinogenesis. It was previously shown that PLA2 group 2A (PLA2G2A) messenger RNA (mRNA) expression is associated with less frequent metastasis and longer survival in gastric adenocarcinoma. This study intends to investigate the effect of PUFAs on the expression of PLA2G2A in patients with gastric cancer. Thirty-four patients with gastric cancer (GC) were randomly divided into two groups. The first group received cisplatin medication. The second group received cisplatin medication and supplements of ω-fatty acids for three courses. The total RNA was extracted from the tissues and cDNA was synthesized. The gene expression of PLA2G2A was evaluated by the real-time polymerase chain reaction (PCR) method. To confirm the changes in gene expression, frozen section was utilized. The frozen tissue samples were sectioned and stained using the immunohistochemistry technique. After chemotherapy and chemotherapy plus supplement, the relative mean of PLA2G2A gene expression increased 1.5 ± 0.5-fold and 7.4 ± 2.6-fold, respectively ( P = 0.006). The relative mean of gene expression in patients who received cisplatin and ω-fatty acids supplement increased more significantly (7.5 ± 3.3-fold) than in patients who received only cisplatin ( P = 0.016). It was found that PUFAs increased the gene and protein expression of PLA2G2A in gastric cancer. Concerning the fact that studies reveal protective function of PLA2G2A in gastric cancer, it is suggested that increased expression of PLA2G2A is helpful. Furthermore, PUFAs can be considered as a useful therapeutic supplement for patients with gastric cancer.

EGFR gene amplification is relatively common and associates with outcome in intestinal adenocarcinoma of the stomach, gastro-oesophageal junction and distal oesophagus

International Nuclear Information System (INIS)

Birkman, Eva-Maria; Ålgars, Annika; Lintunen, Minnamaija; Ristamäki, Raija; Sundström, Jari; Carpén, Olli

2016-01-01

Approximately 50 % of gastric adenocarcinomas belong to a molecular subgroup characterised by chromosomal instability and a strong association with the intestinal histological subtype. This subgroup typically contains alterations in the receptor tyrosine kinase–RAS pathway, for example EGFR or HER2 gene amplifications leading to protein overexpression. In clinical practice, HER2 overexpressing metastatic gastric cancer is known to respond to treatment with anti-HER2 antibodies. By contrast, anti-EGFR antibodies have not been able to provide survival benefit in clinical trials, which, however, have not included patient selection based on the histological subtype or EGFR gene copy number analysis of the tumours. To examine the role of EGFR as a potential biomarker, we studied the prevalence, clinicopathological associations as well as prognostic role of EGFR and HER2 expression and gene amplification in intestinal adenocarcinomas of the stomach, gastro-oesophageal junction and distal oesophagus. Tissue samples from 220 patients were analysed with EGFR and HER2 immunohistochemistry. Those samples with moderate/strong staining intensity were further analysed with silver in situ hybridization to quantify gene copy numbers. The results were associated with clinical patient characteristics and survival. Moderate/strong EGFR protein expression was found in 72/220 (32.7 %) and EGFR gene amplification in 31/220 (14.1 %) of the tumours, while moderate/strong HER2 protein expression was detected in 31/220 (14.1 %) and HER2 gene amplification in 29/220 (13.2 %) of the tumours. EGFR and HER2 genes were co-amplified in eight tumours (3.6 %). EGFR gene amplification was more common in tumours of distal oesophagus/gastro-oesophageal junction/cardia than in those of gastric corpus (p = 0.013). It was associated with shortened time to cancer recurrence (p = 0.026) and cancer specific survival (p = 0.033). EGFR gene amplification is relatively common in intestinal adenocarcinomas

Milk fermented by Propionibacterium freudenreichii induces apoptosis of HGT-1 human gastric cancer cells.

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Fabien J Cousin

Full Text Available Gastric cancer is one of the most common cancers in the world. The "economically developed countries" life style, including diet, constitutes a risk factor favoring this cancer. Diet modulation may lower digestive cancer incidence. Among promising food components, dairy propionibacteria were shown to trigger apoptosis of human colon cancer cells, via the release of short-chain fatty acids acetate and propionate.A fermented milk, exclusively fermented by P. freudenreichii, was recently designed. In this work, the pro-apoptotic potential of this new fermented milk was demonstrated on HGT-1 human gastric cancer cells. Fermented milk supernatant induced typical features of apoptosis including chromatin condensation, formation of apoptotic bodies, DNA laddering, cell cycle arrest and emergence of a subG1 population, phosphatidylserine exposure at the plasma membrane outer leaflet, reactive oxygen species accumulation, mitochondrial transmembrane potential disruption, caspase activation and cytochrome c release. Remarkably, this new fermented milk containing P. freudenreichii enhanced the cytotoxicity of camptothecin, a drug used in gastric cancer chemotherapy.Such new probiotic fermented milk may thus be useful as part of a preventive diet designed to prevent gastric cancer and/or as a food supplement to potentiate cancer therapeutic treatments.

Serum metabolic profiling of human gastric cancer based on gas chromatography/mass spectrometry

International Nuclear Information System (INIS)

Song, Hu; Peng, Jun-Sheng; Yao, Dong-Sheng; Yang, Zu-Li; Liu, Huan-Liang; Zeng, Yi-Ke; Shi, Xian-Ping; Lu, Bi-Yan

2011-01-01

Research on molecular mechanisms of carcinogenesis plays an important role in diagnosing and treating gastric cancer. Metabolic profiling may offer the opportunity to understand the molecular mechanism of carcinogenesis and help to non-invasively identify the potential biomarkers for the early diagnosis of human gastric cancer. The aims of this study were to explore the underlying metabolic mechanisms of gastric cancer and to identify biomarkers associated with morbidity. Gas chromatography/mass spectrometry (GC/MS) was used to analyze the serum metabolites of 30 Chinese gastric cancer patients and 30 healthy controls. Diagnostic models for gastric cancer were constructed using orthogonal partial least squares discriminant analysis (OPLS-DA). Acquired metabolomic data were analyzed by the nonparametric Wilcoxon test to find serum metabolic biomarkers for gastric cancer. The OPLS-DA model showed adequate discrimination between cancer and non-cancer cohorts while the model failed to discriminate different pathological stages (I-IV) of gastric cancer patients. A total of 44 endogenous metabolites such as amino acids, organic acids, carbohydrates, fatty acids, and steroids were detected, of which 18 differential metabolites were identified with significant differences. A total of 13 variables were obtained for their greatest contribution in the discriminating OPLS-DA model [variable importance in the projection (VIP) value >1.0], among which 11 metabolites were identified using both VIP values (VIP >1) and the Wilcoxon test. These metabolites potentially revealed perturbations of glycolysis and of amino acid, fatty acid, cholesterol, and nucleotide metabolism of gastric cancer patients. These results suggest that gastric cancer serum metabolic profiling has great potential in detecting this disease and helping to understand its metabolic mechanisms

Analysis of ABC (D) stratification for screening patients with gastric cancer.

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Kudo, Tomohiro; Kakizaki, Satoru; Sohara, Naondo; Onozato, Yasuhiro; Okamura, Shinichi; Inui, Yoshikatsu; Mori, Masatomo

2011-11-21

To evaluate the value of ABC (D) stratification [combination of serum pepsinogen and Helicobacter pylori (H. pylori) antibody] of patients with gastric cancer. Ninety-five consecutive patients with gastric cancer were enrolled into the study. The serum pepsinogen I (PG I)/pepsinogen II (PG II) and H. pylori antibody levels were measured. Patients were classified into five groups of ABC (D) stratification according to their serological status. Endoscopic findings of atrophic gastritis and histological differentiation were also analyzed in relation to the ABC (D) stratification. The mean patient age was (67.9 ± 8.9) years. Three patients (3.2%) were classified into group A, 7 patients (7.4%) into group A', 27 patients (28.4%) into group B, 54 patients (56.8%) into group C, and 4 patients (4.2%) into group D, respectively. There were only three cases in group A when the patients taking acid proton pump inhibitors and those who had undergone eradication therapy for H. pylori (group A') were excluded. These three cases had mucosal atrophy in the grey zone according to the diagnostic manual of ABC (D) stratification. Histologically, the mean age of the patients with well differentiated adenocarcinoma was significantly higher than that of the patients with poorly differentiated adenocarcinoma (P ABC (D) stratification is a good method for screening patients with gastric cancers. Endoscopy is needed for grey zone cases to check the extent of mucosal atrophy.

Meningeal carcinomatosis as first manifestation of gastric carcinoma

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Romero R, Alfredo E; Mantilla H, Julio C; Melo U, Mario A; Barajas S, Paula A; Chinchilla O Sandra

2009-01-01

Meningeal carcinomatosis is defined as the malignant and widespread infiltration of the meninges due to the planting and growth of cancer cells within the leptomeningeal space. It occurs more frequently in patients with disseminated neoplastic disease, but it may occur after a disease free interval and may even be the first manifestation of cancer. The most common primary tumors in adults are breast (30-50%), lung (15-25%), melanoma (11%) and gastric cancer (0.16-0.69%); in marked contrast with pediatric cases in which lymphocytic leukemia is the most common. The following article describes an autopsy case of a patient with psychiatric symptoms, with no antecedents of importance, with progressive and fatal neurological impairment, whose pathological studies show meningeal carcinomatosis attributable to advanced gastric adenocarcinoma discovered de novo post mortem.

Comparison of the human gastric microbiota in hypochlorhydric states arising as a result of Helicobacter pylori-induced atrophic gastritis, autoimmune atrophic gastritis and proton pump inhibitor use.

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Bryony N Parsons

2017-11-01

Full Text Available Several conditions associated with reduced gastric acid secretion confer an altered risk of developing a gastric malignancy. Helicobacter pylori-induced atrophic gastritis predisposes to gastric adenocarcinoma, autoimmune atrophic gastritis is a precursor of type I gastric neuroendocrine tumours, whereas proton pump inhibitor (PPI use does not affect stomach cancer risk. We hypothesised that each of these conditions was associated with specific alterations in the gastric microbiota and that this influenced subsequent tumour risk. 95 patients (in groups representing normal stomach, PPI treated, H. pylori gastritis, H. pylori-induced atrophic gastritis and autoimmune atrophic gastritis were selected from a cohort of 1400. RNA extracted from gastric corpus biopsies was analysed using 16S rRNA sequencing (MiSeq. Samples from normal stomachs and patients treated with PPIs demonstrated similarly high microbial diversity. Patients with autoimmune atrophic gastritis also exhibited relatively high microbial diversity, but with samples dominated by Streptococcus. H. pylori colonisation was associated with decreased microbial diversity and reduced complexity of co-occurrence networks. H. pylori-induced atrophic gastritis resulted in lower bacterial abundances and diversity, whereas autoimmune atrophic gastritis resulted in greater bacterial abundance and equally high diversity compared to normal stomachs. Pathway analysis suggested that glucose-6-phospahte1-dehydrogenase and D-lactate dehydrogenase were over represented in H. pylori-induced atrophic gastritis versus autoimmune atrophic gastritis, and that both these groups showed increases in fumarate reductase. Autoimmune and H. pylori-induced atrophic gastritis were associated with different gastric microbial profiles. PPI treated patients showed relatively few alterations in the gastric microbiota compared to healthy subjects.

Comparison of the human gastric microbiota in hypochlorhydric states arising as a result of Helicobacter pylori-induced atrophic gastritis, autoimmune atrophic gastritis and proton pump inhibitor use

Science.gov (United States)

Eccles, Richard; Duckworth, Carrie A.; Varro, Andrea

2017-01-01

Several conditions associated with reduced gastric acid secretion confer an altered risk of developing a gastric malignancy. Helicobacter pylori-induced atrophic gastritis predisposes to gastric adenocarcinoma, autoimmune atrophic gastritis is a precursor of type I gastric neuroendocrine tumours, whereas proton pump inhibitor (PPI) use does not affect stomach cancer risk. We hypothesised that each of these conditions was associated with specific alterations in the gastric microbiota and that this influenced subsequent tumour risk. 95 patients (in groups representing normal stomach, PPI treated, H. pylori gastritis, H. pylori-induced atrophic gastritis and autoimmune atrophic gastritis) were selected from a cohort of 1400. RNA extracted from gastric corpus biopsies was analysed using 16S rRNA sequencing (MiSeq). Samples from normal stomachs and patients treated with PPIs demonstrated similarly high microbial diversity. Patients with autoimmune atrophic gastritis also exhibited relatively high microbial diversity, but with samples dominated by Streptococcus. H. pylori colonisation was associated with decreased microbial diversity and reduced complexity of co-occurrence networks. H. pylori-induced atrophic gastritis resulted in lower bacterial abundances and diversity, whereas autoimmune atrophic gastritis resulted in greater bacterial abundance and equally high diversity compared to normal stomachs. Pathway analysis suggested that glucose-6-phospahte1-dehydrogenase and D-lactate dehydrogenase were over represented in H. pylori-induced atrophic gastritis versus autoimmune atrophic gastritis, and that both these groups showed increases in fumarate reductase. Autoimmune and H. pylori-induced atrophic gastritis were associated with different gastric microbial profiles. PPI treated patients showed relatively few alterations in the gastric microbiota compared to healthy subjects. PMID:29095917

Human induced pluripotent stem cells labeled with fluorescent magnetic nanoparticles for targeted imaging and hyperthermia therapy for gastric cancer

International Nuclear Information System (INIS)

Li, Chao; Ruan, Jing; Yang, Meng; Pan, Fei; Gao, Guo; Qu, Su; Shen, You-Lan; Dang, Yong-Jun; Wang, Kan; Jin, Wei-Lin; Cui, Da-Xiang

2015-01-01

Human induced pluripotent stem (iPS) cells exhibit great potential for generating functional human cells for medical therapies. In this paper, we report for use of human iPS cells labeled with fluorescent magnetic nanoparticles (FMNPs) for targeted imaging and synergistic therapy of gastric cancer cells in vivo. Human iPS cells were prepared and cultured for 72 h. The culture medium was collected, and then was co-incubated with MGC803 cells. Cell viability was analyzed by the MTT method. FMNP-labeled human iPS cells were prepared and injected into gastric cancer-bearing nude mice. The mouse model was observed using a small-animal imaging system. The nude mice were irradiated under an external alternating magnetic field and evaluated using an infrared thermal mapping instrument. Tumor sizes were measured weekly. iPS cells and the collected culture medium inhibited the growth of MGC803 cells. FMNP-labeled human iPS cells targeted and imaged gastric cancer cells in vivo, as well as inhibited cancer growth in vivo through the external magnetic field. FMNP-labeled human iPS cells exhibit considerable potential in applications such as targeted dual-mode imaging and synergistic therapy for early gastric cancer

[Conversion Therapy Using Etoposide and Cisplatin Chemotherapy for Liver Metastases from Advanced Gastric Mixed Adenoneuroendocrine Carcinoma - A Case Report].

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Inaba, Yoko; Fujita, Maiko; Ninomiya, Riki; Hashimoto, Daijo

2017-11-01

Gastric mixed adenoneuroendocrine carcinoma(MANEC)with multiple liver metastases is a rare condition with most data being derived from case reports. We present a case with liver metastases from gastric MANEC that respond remarkably to chemotherapy. Sixty-one-year-old male with severe anemia referred to surgical consultation due to advanced gastric cancer with multiple liver metastases. To relieve uncontrollable tumor bleeding, simple distal gastrectomy for symptom palliation was performed. Based on the tentative diagnosis with gastric poorly differentiated adenocarcinoma, a course of TS-1 and oxaliplatin therapy was administrated. Thereafter final diagnosis with neuroendocrine carcinoma with tubular adenocarcinoma was made, and the chemotherapy was switched to etoposide and cisplatin. Follow up abdominal CT scan after the third course of the therapy showed remarkable tumor shrinkages(PR). In anticipation of the chemotherapy effects in the adjuvant setting, we performed liver metastasectomy for curative intent. Two of 6 resected liver specimens showed no viable cancer cells at all (pCR). However, immediately after the surgery, multiple liver metastases developed, and the recurrent masses had kept growing up rapidly. The third line carboplatin and etoposide chemotherapy was given once but was withdrawn because of bone marrow suppression. At the present, the patient is alive with recurrent diseases for 18 months after initial diagnosis.

Failure of ethamsylate to reduce aspirin-induced gastric mucosal bleeding in humans.

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Daneshmend, T K; Stein, A G; Bhaskar, N K; Hawkey, C J

1989-07-01

1. We investigated the effect of the haemostatic agent ethamsylate on aspirin-induced gastric mucosal bleeding. 2. Eighteen healthy subjects were studied three times: at the end of 48 h periods of treatment with (a) placebo, (b) aspirin 600 mg four times daily, (9 doses) and (c) aspirin 600 mg four times daily with each dose preceded by ethamsylate 500 mg. 3. At the end of each treatment period gastric mucosal bleeding into timed gastric washings was quantified using the orthotolidine reaction. 4. Aspirin increased bleeding from a rate on placebo of 1.2 microliters 10 min-1 geometric mean (95% confidence limits) (0.7-1.8) microliters 10 min-1 to 20.0 (11.6-34.2) microliters 10 min-1, (P less than 0.01). The rate of bleeding after aspirin preceded by ethamsylate [14.1 (8.5-23.4) microliters 10 min-1] was not significantly different from that after aspirin alone. 5. We conclude that ethamsylate does not reduce acute aspirin-induced gastric mucosal bleeding in healthy humans.

Nitrergic Pathway Is the Main Contributing Mechanism in the Human Gastric Fundus Relaxation: An In Vitro Study.

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Yang Won Min

Full Text Available Human gastric fundus relaxation is mediated by intrinsic inhibitory pathway. We investigated the roles of nitrergic and purinergic pathways, two known inhibitory factors in gastric motility, on spontaneous and nerve-evoked contractions in human gastric fundus muscles.Gastric fundus muscle strips (12 circular and 13 longitudinal were obtained from patients without previous gastrointestinal motility disorder who underwent gastrectomy for stomach cancer. Using these specimens, we examined basal tone, peak, amplitude, and frequency of spontaneous contractions, and peak and nadir values under electrical field stimulation (EFS, 150 V, 0.3 ms, 10 Hz, 20 s. To examine responses to purinergic and nitrergic inhibition without cholinergic innervation, atropine (muscarinic antagonist, 1 μM, MRS2500 (a purinergic P2Y1 receptor antagonist, 1 μM, and N-nitro-L-arginine (L-NNA, a nitric oxide synthase inhibitor, 100 μM were added sequentially for spontaneous and electrically-stimulated contractions. Tetrodotoxin was used to confirm any neuronal involvement.In spontaneous contraction, L-NNA increased basal tone and peak in both muscle layers, while amplitude and frequency were unaffected. EFS (up to 10 Hz uniformly induced initial contraction and subsequent relaxation in a frequency-dependent manner. Atropine abolished initial on-contraction and induced only relaxation during EFS. While MRS2500 showed no additional influence, L-NNA reversed relaxation (p = 0.012 in circular muscle, and p = 0.006 in longitudinal muscle. Tetrodotoxin abolished any EFS-induced motor response.The relaxation of human gastric fundus muscle is reduced by nitrergic inhibition. Hence, nitrergic pathway appears to be the main mechanism for the human gastric fundus relaxation.

Inhibitory effect of piperine on Helicobacter pylori growth and adhesion to gastric adenocarcinoma cells

OpenAIRE

Tharmalingam, Nagendran; Kim, Sa-Hyun; Park, Min; Woo, Hyun Jun; Kim, Hyun Woo; Yang, Ji Yeong; Rhee, Ki-Jong; Kim, Jong Bae

2014-01-01

Background Piperine is a compound comprising 5-9% of black pepper (Piper nigrum), which has a variety of biological roles related to anticancer activities. Helicobacter pylori has been classified as a gastric carcinogen, because it causes gastritis and gastric cancer by injecting the virulent toxin CagA and translocating VacA. The present study investigated the inhibitory action of piperine on H. pylori growth and adhesion. Methods Inhibition of H. pylori growth was determined by the broth ma...

Effect of hGC-MSCs from human gastric cancer tissue on cell proliferation, invasion and epithelial-mesenchymal transition in tumor tissue of gastric cancer tumor-bearing mice.

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Song, Lin; Zhou, Xin; Jia, Hong-Jun; Du, Mei; Zhang, Jin-Ling; Li, Liang

2016-08-01

To study the effect of hGC-MSCs from human gastric cancer tissue on cell proliferation, invasion and epithelial-mesenchymal transition in tumor tissue of gastric cancer tumor-bearing mice. BABL/c nude mice were selected as experimental animals and gastric cancer tumor-bearing mice model were established by subcutaneous injection of gastric cancer cells, randomly divided into different intervention groups. hGC-MSCs group were given different amounts of gastric cancer cells for subcutaneous injection, PBS group was given equal volume of PBS for subcutaneous injection. Then tumor tissue volume were determined, tumor-bearing mice were killed and tumor tissues were collected, mRNA expression of proliferation, invasion, EMT-related molecules were determined. 4, 8, 12, 16, 20 d after intervention, tumor tissue volume of hGC-MSCs group were significantly higher than those of PBS group and the more the number of hGC-MSCs, the higher the tumor tissue volume; mRNA contents of Ki-67, PCNA, Bcl-2, MMP-2, MMP-7, MMP-9, MMP-14, N-cadherin, vimentin, Snail and Twist in tumor tissue of hGC-MSCs group were higher than those of PBS group, and mRNA contents of Bax, TIMP1, TIMP2 and E-cadherin were lower than those of PBS group. hGC-MSCs from human gastric cancer tissue can promote the tumor growth in gastric cancer tumor-bearing mice, and the molecular mechanism includes promoting cell proliferation, invasion and epithelial-mesenchymal transition. Copyright © 2016 Hainan Medical College. Production and hosting by Elsevier B.V. All rights reserved.

Echinophora platyloba DC (Apiaceae crude extract induces apoptosis in human prostate adenocarcinoma cells (PC 3

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Fatemeh Zare Shahneh

2014-10-01

Full Text Available Background: Prostate cancer is the second leading malignancy worldwide and the second prominent cause of cancer-related deaths among men. Therefore, there is a serious necessity for finding advanced alternative therapeutic measures against this lethal malignancy. In this article, we report the cytotoxicity and the mechanism of cell death of the methanolic extract prepared from Echinophora platyloba DC plant against human prostate adenocarcinoma PC 3 cell line and Human Umbilical Vein Endothelial Cells HUVEC cell line. Methods: Cytotoxicity and viability of the methanolic extract were assessed by 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assay and dye exclusion assay. Cell death enzyme-linked immunosorbent assay (ELISA was employed to quantify the nucleosome production resulting from nuclear DNA fragmentation during apoptosis and determine whether the mechanism involves induction of apoptosis or necrosis. The cell death was identified as apoptosis using terminal deoxynucleotidyl transferase (TdT-mediated dUTP nick end labeling (TUNEL assay and DNA fragmentation gel electrophoresis. Results: E. platyloba could decrease cell viability in malignant cells in a dose- and time-dependent manner. The IC50 values against PC 3 were determined as 236.136 ± 12.4, 143.400 ± 7.2, and 69.383 ± 1.29 μg/ml after 24, 36, and 48 h, respectively, but there was no significant activity in HUVEC normal cell (IC50 > 800 μg/ml. Morphological characterizations and DNA laddering assay showed that the methanolic extract treated cells displayed marked apoptotic characteristics such as nuclear fragmentation, appearance of apoptotic bodies, and DNA laddering fragment. Increase in an early apoptotic population was observed in a dose-dependent manner. PC 3 cell death elicited by the extract was found to be apoptotic in nature based a clear indication of TUNEL assay and gel electrophoresis DNA fragmentation, which is a hallmark of apoptosis

Current approaches to gastric cancer in Peru and Mexico.

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Santos, Erlan

2017-01-01

In Peru, the incidence of gastric cancer is reported to be around 15.8 per 100,000 inhabitants and it is the second most common oncological disease in men and the third one in women. Additionally, a high mortality index was reported, especially among poor people. To address this issue, in 2008, Peru initiated several insurance treatment plans of oncological diseases with promising results. In Mexico, there is a high predominance of gastric cancer in male gender compared to female gender, even reaching a 2/1 ratio, and the detection rate of early gastric cancer is low (10% to 20%) which results in a mainly palliative treatment with an overall survival rate in 5 years about 10% to 15% only. In Peru, the average age at diagnosis is around 62.96±14.75 years old and the most frequent symptoms includes abdominal pain, indigestion, loss of appetite, weight loss and gastrointestinal bleeding, while in Mexico, some studies reported an average age at diagnosis around 60.3±4.1 years old (range, 23-78 years old) and the most frequent symptoms were postprandial fullness (74.4%), abdominal pain (37.2%), weight loss (18.6%), and melena (4.6%). The anemia rate was 65.1% with a mean Hb level of 6.14 g/dL. In Peru, the most common gastric cancer type is the intestinal-type adenocarcinoma (around 34%), followed by the diffuse-type adenocarcinoma (18.7%), whilst among Mexicans, the diffuse-type was reported in 55.2% of cases, the intestinal-type was reported in 28.2% and the undifferentiated-type corresponded to 6%. In both, Peru and Mexico, 90% of the associated factors includes tabaquismo, diets rich in salt, smoked foods, and a sedentary lifestyle. Family inheritance and advanced age and pharmacological-resistant Helicobacter pylori infection are also important. Poverty has been heavily associated with a higher incidence of gastric cancer. The management of gastric cancer patients in Peru is carried out by general surgeons or general surgical oncologists. In recent years, efforts

Ibuprofen delivered by poly(lactic-co-glycolic acid) (PLGA) nanoparticles to human gastric cancer cells exerts antiproliferative activity at very low concentrations

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Bonelli, Patrizia; Tuccillo, Franca M; Federico, Antonella; Napolitano, Maria; Borrelli, Antonella; Melisi, Daniela; Rimoli, Maria G; Palaia, Raffaele; Arra, Claudio; Carinci, Francesco

2012-01-01

Purpose Epidemiological, clinical, and laboratory studies have suggested that ibuprofen, a commonly used nonsteroidal anti-inflammatory drug, inhibits the promotion and proliferation of certain tumors. Recently, we demonstrated the antiproliferative effects of ibuprofen on the human gastric cancer cell line MKN-45. However, high doses of ibuprofen were required to elicit these antiproliferative effects in vitro. The present research compared the antiproliferative effects of ibuprofen delivered freely and released by poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) in MKN-45 cells. Methods MKN-45 human gastric adenocarcinoma cells were treated with ibuprofen-loaded PLGA NPs. The proliferation of MKN-45 cells was then assessed by cell counting. The uptake of NPs was imaged by fluorescence microscopy and flow cytometry. The release of ibuprofen from ibuprofen-loaded PLGA NPs in the cells was evaluated by gas chromatography–mass spectrometry. Results Dramatic inhibition of cellular proliferation was observed in cells treated with ibuprofen-loaded PLGA NPs versus those treated with free ibuprofen at the same concentration. The localization of NPs was cytoplasmic. The initiation of ibuprofen release was rapid, commencing within 2 hours, and then increased slowly over time, reaching a maximum concentration at 24 hours. The inhibition of proliferation was confirmed to be due to the intracellular release of ibuprofen from the NPs. Using PLGA NPs as carriers, ibuprofen exerted an antiproliferative activity at concentrations > 100 times less than free ibuprofen, suggesting greater efficiency and less cellular toxicity. In addition, when carried by PLGA NPs, ibuprofen more quickly induced the expression of transcripts involved in proliferation and invasiveness processes. Conclusion Ibuprofen exerted an antiproliferative effect on MKN-45 cells at low concentrations. This effect was achieved using PLGA NPs as carriers of low doses of ibuprofen. PMID:23180963

Adenocarcinoma of the third portion of the duodenum in a man with CREST syndrome

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Fragulidis Georgios

2008-10-01

Full Text Available Abstract Background CREST (Calcinosis, Raynaud's phenomenon, Esophageal dysmotility, Sclerodactyly and Telangiectasias syndrome has been rarely associated with other malignancies (lung, esophagus.This is the first report of a primary adenocarcinoma of the third portion of the duodenum in a patient with CREST syndrome. Case presentation A 54-year-old male patient with CREST syndrome presented with colicky postprandial pain of the upper abdomen, diminished food uptake and a 6-Kg-body weight loss during the previous 2 months. An ulcerative lesion in the third portion of the duodenum was revealed during duodenoscopy, with a diagnosis of adenocarcinoma on biopsy specimen histology. The patient underwent a partial pancreatoduodenectomy. No adjuvant therapy was instituted and follow-up is negative for local recurrence or metastases 21 months postoperatively. Conclusion CREST syndrome has been associated with colon cancer, gastric polyps, familial adenomatous polyposis (FAP syndrome and Crohn's disease; however, this is the first report of a primary adenocarcinoma of the duodenum in a patient with CREST syndrome. However, any etiologic relationship remains to be further investigated.

Transduction motif analysis of gastric cancer based on a human signaling network

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Liu, G.; Li, D.Z.; Jiang, C.S.; Wang, W. [Fuzhou General Hospital of Nanjing Command, Department of Gastroenterology, Fuzhou, China, Department of Gastroenterology, Fuzhou General Hospital of Nanjing Command, Fuzhou (China)

2014-04-04

To investigate signal regulation models of gastric cancer, databases and literature were used to construct the signaling network in humans. Topological characteristics of the network were analyzed by CytoScape. After marking gastric cancer-related genes extracted from the CancerResource, GeneRIF, and COSMIC databases, the FANMOD software was used for the mining of gastric cancer-related motifs in a network with three vertices. The significant motif difference method was adopted to identify significantly different motifs in the normal and cancer states. Finally, we conducted a series of analyses of the significantly different motifs, including gene ontology, function annotation of genes, and model classification. A human signaling network was constructed, with 1643 nodes and 5089 regulating interactions. The network was configured to have the characteristics of other biological networks. There were 57,942 motifs marked with gastric cancer-related genes out of a total of 69,492 motifs, and 264 motifs were selected as significantly different motifs by calculating the significant motif difference (SMD) scores. Genes in significantly different motifs were mainly enriched in functions associated with cancer genesis, such as regulation of cell death, amino acid phosphorylation of proteins, and intracellular signaling cascades. The top five significantly different motifs were mainly cascade and positive feedback types. Almost all genes in the five motifs were cancer related, including EPOR, MAPK14, BCL2L1, KRT18, PTPN6, CASP3, TGFBR2, AR, and CASP7. The development of cancer might be curbed by inhibiting signal transductions upstream and downstream of the selected motifs.

Milk Fermented by Propionibacterium freudenreichii Induces Apoptosis of HGT-1 Human Gastric Cancer Cells

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Cousin, Fabien J.; Jouan-Lanhouet, Sandrine; Dimanche-Boitrel, Marie-Thérèse; Corcos, Laurent; Jan, Gwénaël

2012-01-01

Background Gastric cancer is one of the most common cancers in the world. The “economically developed countries” life style, including diet, constitutes a risk factor favoring this cancer. Diet modulation may lower digestive cancer incidence. Among promising food components, dairy propionibacteria were shown to trigger apoptosis of human colon cancer cells, via the release of short-chain fatty acids acetate and propionate. Methodology/Principal Findings A fermented milk, exclusively fermented by P. freudenreichii, was recently designed. In this work, the pro-apoptotic potential of this new fermented milk was demonstrated on HGT-1 human gastric cancer cells. Fermented milk supernatant induced typical features of apoptosis including chromatin condensation, formation of apoptotic bodies, DNA laddering, cell cycle arrest and emergence of a subG1 population, phosphatidylserine exposure at the plasma membrane outer leaflet, reactive oxygen species accumulation, mitochondrial transmembrane potential disruption, caspase activation and cytochrome c release. Remarkably, this new fermented milk containing P. freudenreichii enhanced the cytotoxicity of camptothecin, a drug used in gastric cancer chemotherapy. Conclusions/Significance Such new probiotic fermented milk may thus be useful as part of a preventive diet designed to prevent gastric cancer and/or as a food supplement to potentiate cancer therapeutic treatments. PMID:22442660

Gastric cancers of Western European and African patients show different patterns of genomic instability

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Mulder Chris JJ

2011-01-01

Full Text Available Abstract Background Infection with H. pylori is important in the etiology of gastric cancer. Gastric cancer is infrequent in Africa, despite high frequencies of H. pylori infection, referred to as the African enigma. Variation in environmental and host factors influencing gastric cancer risk between different populations have been reported but little is known about the biological differences between gastric cancers from different geographic locations. We aim to study genomic instability patterns of gastric cancers obtained from patients from United Kingdom (UK and South Africa (SA, in an attempt to support the African enigma hypothesis at the biological level. Methods DNA was isolated from 67 gastric adenocarcinomas, 33 UK patients, 9 Caucasian SA patients and 25 native SA patients. Microsatellite instability and chromosomal instability were analyzed by PCR and microarray comparative genomic hybridization, respectively. Data was analyzed by supervised univariate and multivariate analyses as well as unsupervised hierarchical cluster analysis. Results Tumors from Caucasian and native SA patients showed significantly more microsatellite instable tumors (p Conclusions Gastric cancers from SA and UK patients show differences in genetic instability patterns, indicating possible different biological mechanisms in patients from different geographical origin. This is of future clinical relevance for stratification of gastric cancer therapy.

Exogenous wild type p53 gene affects radiosensitivity of human lung adenocarcinoma cell line under hypoxia

International Nuclear Information System (INIS)

Wang Jianhua; Wang Feng; Liu Yongping; Zhang Yaping; Ni Yan; Li Shirong

2008-01-01

Objective: To evaluate the effect of exogenous wild type p53 (wtp53) gene on radiosensitivity of human lung adenocarcinoma cell line under hypoxia. Methods: Human lung adenocarcinoma cell line A549 was transfected with adenovirus carrying recombinant exogenous wtp53. Four irradiation groups were studied: normal cell (Group A), wtp53 transfected cell (Group B), normal cell under hypoxia (Group C) and wtp53 transfected cell under hypoxia(Group D). Cells were irradiated with 9 MeV electron beams. Cellular survival fraction was analyzed. Multi-target single-hit model was used to plot the survival curve. D 0 , D q , oxygen enhancement ratio (OER), sensitizing enhancement ratio (SER) and other parameters were used to evaluate the effects of wtp53 gene on radiosensitivity of A549. The cell apoptotic rate of each group was examined by flow cytometry. Results: OER was 1.75 and 0.81 before and after wtp53 transfection. SER was 1.77 in oxic circumstance and 3.84 under hypoxia. The cell apoptotic rate of Group A and B was lower than Group C and D (F=7.92, P=0.048), with Group A lower than B and Group C lower than D (F=82.50, P=0.001). But Group B and D were similar(t=2.04, P=0.111). Conclusions: Hypoxia can increase the radiation resistance of lung adenocarcinoma cell line A549. The wtp53 can promote apoptosis and improve tumor radiosensitivity, especially under hypoxia. (authors)

Preoperative chemoradiotherapy for locally advanced gastric cancer

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Pepek Joseph M

2013-01-01

Full Text Available Abstract Background To examine toxicity and outcomes for patients treated with preoperative chemoradiotherapy (CRT for gastric cancer. Methods Patients with gastroesophageal (GE junction (Siewert type II and III or gastric adenocarcinoma who underwent neoadjuvant CRT followed by planned surgical resection at Duke University between 1987 and 2009 were reviewed. Overall survival (OS, local control (LC and disease-free survival (DFS were estimated using the Kaplan-Meier method. Toxicity was graded according to the Common Toxicity Criteria for Adverse Events version 4.0. Results Forty-eight patients were included. Most (73% had proximal (GE junction, cardia and fundus tumors. Median radiation therapy dose was 45 Gy. All patients received concurrent chemotherapy. Thirty-six patients (75% underwent surgery. Pathologic complete response and R0 resection rates were 19% and 86%, respectively. Thirty-day surgical mortality was 6%. At 42 months median follow-up, 3-year actuarial OS was 40%. For patients undergoing surgery, 3-year OS, LC and DFS were 50%, 73% and 41%, respectively. Conclusions Preoperative CRT for gastric cancer is well tolerated with acceptable rates of perioperative morbidity and mortality. In this patient cohort with primarily advanced disease, OS, LC and DFS rates in resected patients are comparable to similarly staged, adjuvantly treated patients in randomized trials. Further study comparing neoadjuvant CRT to standard treatment approaches for gastric cancer is indicated.

Preoperative chemoradiotherapy for locally advanced gastric cancer

International Nuclear Information System (INIS)

Pepek, Joseph M; Chino, Junzo P; Willett, Christopher G; Palta, Manisha; Blazer III, Dan G; Tyler, Douglas S; Uronis, Hope E; Czito, Brian G

2013-01-01

To examine toxicity and outcomes for patients treated with preoperative chemoradiotherapy (CRT) for gastric cancer. Patients with gastroesophageal (GE) junction (Siewert type II and III) or gastric adenocarcinoma who underwent neoadjuvant CRT followed by planned surgical resection at Duke University between 1987 and 2009 were reviewed. Overall survival (OS), local control (LC) and disease-free survival (DFS) were estimated using the Kaplan-Meier method. Toxicity was graded according to the Common Toxicity Criteria for Adverse Events version 4.0. Forty-eight patients were included. Most (73%) had proximal (GE junction, cardia and fundus) tumors. Median radiation therapy dose was 45 Gy. All patients received concurrent chemotherapy. Thirty-six patients (75%) underwent surgery. Pathologic complete response and R0 resection rates were 19% and 86%, respectively. Thirty-day surgical mortality was 6%. At 42 months median follow-up, 3-year actuarial OS was 40%. For patients undergoing surgery, 3-year OS, LC and DFS were 50%, 73% and 41%, respectively. Preoperative CRT for gastric cancer is well tolerated with acceptable rates of perioperative morbidity and mortality. In this patient cohort with primarily advanced disease, OS, LC and DFS rates in resected patients are comparable to similarly staged, adjuvantly treated patients in randomized trials. Further study comparing neoadjuvant CRT to standard treatment approaches for gastric cancer is indicated

Effects of the H(2)-receptor antagonist ranitidine on gastric motor function after a liquid meal in healthy humans

DEFF Research Database (Denmark)

Madsen, Jan Lysgård; Graff, J

2008-01-01

, on gastric volume and gastric emptying after a liquid meal in healthy humans. Material and methods. Twelve healthy volunteers participated in a randomized crossover study with 50 mg ranitidine as a bolus intravenously versus no medication. Gastric volume at baseline was determined with single photon emission...... computed tomography (SPECT) after intravenous injection of 99(m)Tc-pertechnetate. After ingestion of a 600-mL liquid meal radiolabelled with (111)In-diethylenetriaminepentaacetic acid, dual-isotope technique with SPECT and planar imaging assessed gastric volume as well as gastric emptying. Results....... Ranitidine did not change gastric volume before the meal, nor at 0 h or 1 h after it. Furthermore, ranitidine did not influence gastric retention of meal components after 0.5 h and 1 h. Conclusions. Intravenous bolus injection of 50 mg ranitidine does not modify gastric volume or gastric emptying after a 600...

Fatal pulmonary thromboembolism in gastrectomy intraoperative procedures by gastric adenocarcinoma: case report Tromboembolismo pulmonar fatal no intra-operatório de gastrectomia por adenocarcinoma gástrico: relato de caso

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Cláudio Bresciani

1999-08-01

Full Text Available The case of a patient with gastric adenocarcinoma with indication for gastrectomy is reported. The surgery took place without complications. A palliative, subtotal gastrectomy was performed after para-aortic lymph nodes compromised by neoplasm were found, which was confirmed by pathological exam of frozen sections carried out during the intervention. At the end of the gastroenteroanastomosis procedure, the patient began to show intense bradycardia: 38 beats per minute (bpm, arterial hypotension, changes in the electrocardiogram's waveform (upper unlevelling of segment ST, and cardiac arrest. Resuscitation maneuvers were performed with temporary success. Subsequently, the patient had another circulatory breakdown and again was recovered. Finally, the third cardiac arrest proved to be irreversible, and the intra-operative death occurred. Necropsy showed massive pulmonary embolism. The medical literature has recommended heparinization of patients, in an attempt to avoid pulmonary thromboembolism following major surgical interventions. However, in the present case, heparinization would have been insufficient to prevent death. This case indicates that it is necessary to develop preoperative propedeutics for diagnosing the presence of venous thrombi with potential to migrate, causing pulmonary thromboembolism (PTE. If such thrombi could be detected, preventative measures, such as filter installation in the Cava vein could be undertaken.Relata-se um caso de paciente com adenocarcinoma gástrico com indicação de gastrectomia. O ato operatório transcorreu sem anormalidades. Foi realizada gastrectomia subtotal paliativa, pois encontrou-se linfonodos para-aórticos comprometidos pela neoplasia, confirmado por exame anátomo-patológico de congelação realizado no decorrer da intervenção. Ao fim da confecção da gastroêntero-anastomose o paciente passou a apresentar bradicardia intensa: 38 batimentos por minuto (bpm, hipotensão arterial, altera

Identification of DNA methylation changes associated with human gastric cancer

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Park Jung-Hoon

2011-12-01

Full Text Available Abstract Background Epigenetic alteration of gene expression is a common event in human cancer. DNA methylation is a well-known epigenetic process, but verifying the exact nature of epigenetic changes associated with cancer remains difficult. Methods We profiled the methylome of human gastric cancer tissue at 50-bp resolution using a methylated DNA enrichment technique (methylated CpG island recovery assay in combination with a genome analyzer and a new normalization algorithm. Results We were able to gain a comprehensive view of promoters with various CpG densities, including CpG Islands (CGIs, transcript bodies, and various repeat classes. We found that gastric cancer was associated with hypermethylation of 5' CGIs and the 5'-end of coding exons as well as hypomethylation of repeat elements, such as short interspersed nuclear elements and the composite element SVA. Hypermethylation of 5' CGIs was significantly correlated with downregulation of associated genes, such as those in the HOX and histone gene families. We also discovered long-range epigenetic silencing (LRES regions in gastric cancer tissue and identified several hypermethylated genes (MDM2, DYRK2, and LYZ within these regions. The methylation status of CGIs and gene annotation elements in metastatic lymph nodes was intermediate between normal and cancerous tissue, indicating that methylation of specific genes is gradually increased in cancerous tissue. Conclusions Our findings will provide valuable data for future analysis of CpG methylation patterns, useful markers for the diagnosis of stomach cancer, as well as a new analysis method for clinical epigenomics investigations.

Glucagon-like peptide 2 stimulates glucagon secretion, enhances lipid absorption, and inhibits gastric acid secretion in humans

DEFF Research Database (Denmark)

Meier, Juris J; Nauck, Michael A; Pott, Andrea

2006-01-01

or placebo during the ingestion of a solid test meal. Gastric emptying was determined using a 13C-sodium-octanote breath test. Plasma concentrations of glucose, insulin, C-peptide, glucagon, GLP-2, free fatty acids, free glycerol, and triglycerides were determined. RESULTS: GLP-2 administration led...... (P = .07). GLP-2 administration caused an approximately 15% reduction in pentagastrin-stimulated gastric acid and chloride secretion (P gastric emptying was not affected (P = .99). CONCLUSIONS: GLP-2 reduces gastric acid secretion but does not seem to have an influence on gastric......BACKGROUND & AIMS: The gut-derived peptide glucagon-like peptide 2 (GLP-2) has been suggested as a potential drug candidate for the treatment of various intestinal diseases. However, the acute effects of GLP-2 on gastric functions as well as on glucose and lipid homeostasis in humans are less well...

Tumor-specific apoptotic gene targeting overcomes radiation resistance in esophageal adenocarcinoma

International Nuclear Information System (INIS)

Chang, Joe Y.; Zhang Xiaochun; Komaki, Ritsuko; Cheung, Rex; Fang Bingliang

2006-01-01

Purpose: To overcome radiation resistance in esophageal adenocarcinoma by tumor-specific apoptotic gene targeting using tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Methods and Materials: Adenoviral vector Ad/TRAIL-F/RGD with a tumor-specific human telomerase reverse transcription promoter was used to transfer TRAIL gene to human esophageal adenocarcinoma and normal human lung fibroblastic cells (NHLF). Activation of apoptosis was analyzed by Western blot, fluorescent activated cell sorting, and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate labeling (TUNEL) assay. A human esophageal adenocarcinoma mouse model was treated with intratumoral injections of Ad/TRAIL-F/RGD plus local radiotherapy. Results: The combination of Ad/TRAIL-F/RGD and radiotherapy increased the cell-killing effect in all esophageal adenocarcinoma cell lines but not in NHLF cells. This combination also significantly reduced clonogenic formation (p < 0.05) and increased sub-G1 deoxyribonucleic acid accumulation in cancer cells (p < 0.05). Activation of apoptosis by Ad/TRAIL-F/RGD plus radiotherapy was demonstrated by activation of caspase-9, caspase-8, and caspase-3 and cleaved poly (adenosine diphosphate-ribose) polymerase in vitro and TUNEL assay in vivo. Combined Ad/TRAIL-F/RGD and radiotherapy dramatically inhibited tumor growth and prolonged mean survival in the esophageal adenocarcinoma model to 31.6 days from 16.7 days for radiotherapy alone and 21.5 days for Ad/TRAIL-F/RGD alone (p < 0.05). Conclusions: The combination of tumor-specific TRAIL gene targeting and radiotherapy enhances the effect of suppressing esophageal adenocarcinoma growth and prolonging survival

Prevalence and importance of nodal micrometastasis in patients with gastric adenocarcinoma

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Bjelović Miloš

2004-01-01

Full Text Available Micrometastasis is a microscopic (less than 2 mm deposit of malignant cells separated from the primary tumor. The incidence and importance of occult perigastric lymph node involvement were analyzed in 26 pNO patients using the prospective method. The occult lymph node involvement was detected by immunohistochemical method using the anticyto-keratin 8/18 antibody. Prevalence of clinically significant occult lymph node involvement (Mi+ was statistically significant, and found in 38.5% of pNO patients. Out of tumor characteristics analyzed as possible predictors of occult lymph node involvement, the histological grade (GH and the involvement of lymphatic vessels within gastric wall (pLl had significant effect on the respective evaluation. The patients with histological grade 3 and 4 had occult lymph node involvement more often than those with grade 1 and 2 (p<0.05. More than 60% of pL1 patients had occult lymph node involvement LN (Mi+. Due to high prevalence of micrometastatic lymph node involvement, detection with specific immunohistochemical or molecular biology techniques should be a part of routine specimen examination in patients with pNO gastric cancer.

Human gastric emptying and colonic filling of solids characterized by a new method

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Camilleri, M.; Colemont, L.J.; Phillips, S.F.; Brown, M.L.; Thomforde, G.M.; Chapman, N.; Zinsmeister, A.R. (Mayo Clinic and Foundation, Rochester, MN (USA))

1989-08-01

Our first aim was to compare {sup 111}In-labeled Amberlite IR-12OP resin pellets and {sup 131}I-labeled fiber in the assessment of gastric and small bowel transit and colonic filling in healthy humans. Both radiolabels were highly stable for 3 h in an in vitro stomach model and remained predominantly bound to solid phase of stools collected over 5 days (90.5 +/- 2.1 (SE)% for {sup 131}I and 87.4 +/- 1.4% for {sup 111}In). The lag phase of gastric emptying was shorter for {sup 111}In-pellets (30 +/- 11 min compared with 58 +/- 12 min for {sup 131}I-fiber, P less than 0.05). However, the slope of the postlag phase of gastric emptying and the half time of small bowel transit were not significantly different for {sup 111}In-pellets and {sup 131}I-fiber. Filling of the colon was characterized by bolus movements of the radiolabel (10-80% range, 26% mean) followed by plateaus (periods of no movement of isotope into colon lasting 15-120 min, range; 51 min, mean). Half of the bolus movements occurred within 1 h of the intake of a second meal. Thus {sup 111}In-labeled Amberlite pellets provide an excellent marker for the study of gastric and small bowel transit and colonic filling in humans. The ileum acts as a reservoir and transfers boluses of variable sizes into the colon, often soon after the intake of a subsequent meal.

Localized amyloidosis of the stomach mimicking a superficial gastric cancer.

Science.gov (United States)

Kagawa, Miwako; Fujino, Yasuteru; Muguruma, Naoki; Murayama, Noriaki; Okamoto, Koichi; Kitamura, Shinji; Kimura, Tetsuo; Kishi, Kazuhiro; Miyamoto, Hiroshi; Uehara, Hisanori; Takayama, Tetsuji

2016-06-01

A 73-year-old man was referred to our hospital for further examination of a depressed lesion in the stomach found by cancer screening gastroscopy. A barium upper gastrointestinal series showed an area of irregular mucosa measuring 15 mm on the anterior wall of the gastric body. Esophagogastroduodenoscopy revealed a 15 mm depressed lesion on the anterior wall of the lower gastric body. We suspected an undifferentiated adenocarcinoma from the appearance and took some biopsies. However, histology of the specimens revealed amyloidal deposits in the submucosal layer without malignant findings. Congo red staining was positive for amyloidal protein and green birefringence was observed under polarized light microscopy. Congo red staining with prior potassium permanganate incubation confirmed the light chain (AL) amyloid type. There were no amyloid deposits in the colon or duodenum. Computed tomography of the chest, abdomen, and pelvis showed no remarkable findings. Thus, this case was diagnosed as a localized gastric amyloidosis characterized by AL type amyloid deposition in the mucosal or submucosal layer. As the clinical outcome of gastric AL amyloidosis seems favorable, this case is scheduled for periodic examination to recognize potential disease progression and has been stable for 2 years.

Prognostic value of Laurén classification and c-erbB-2 oncogene overexpression in adenocarcinoma of the esophagus and gastroesophageal junction

NARCIS (Netherlands)

Polkowski, W.; van Sandick, J. W.; Offerhaus, G. J.; ten Kate, F. J.; Mulder, J.; Obertop, H.; van Lanschot, J. J.

1999-01-01

The prognostic value of the Laurén classification and of c-erbB-2 oncogene overexpression has been described for gastric cancer. The aim of this study was to investigate the clinical significance of these factors in adenocarcinoma of the esophagus and/or gastroesophageal junction (GEJ). Forty-one

NFAT5 promotes proliferation and migration of lung adenocarcinoma cells in part through regulating AQP5 expression

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Guo, Kai, E-mail: gk161@163.com [Department of Respiration, Tangdu Hospital, Fourth Military Medical University, Xi' an 710038 (China); Department of Respiration, 161th Hospital, PLA, Wuhan 430015 (China); Jin, Faguang, E-mail: jinfag@fmmu.edu.cn [Department of Respiration, Tangdu Hospital, Fourth Military Medical University, Xi' an 710038 (China)

2015-09-25

The osmoregulated transcription factor nuclear factor of activated T-cells 5(NFAT5), has been found to play important roles in the development of many kinds of human cancers, including breast cancer, colon carcinoma, renal cell carcinoma and melanoma. The aim of the present study was to determine whether NFAT5 is involved in the proliferation and migration of lung adenocarcinoma cells. We found that NFAT5 was upregulated in lung adenocarcinoma cells and knockdown of NFAT5 decreased proliferation and migration of the cells, accompanied by a significant reduction in the expression of AQP5. AQP5 was upregulated in lung adenocarcinoma cells and knockdown of AQP5 also inhibited proliferation and migration of the cells as knockdown of NFAT5 did. Moreover, overexpression of NFAT5 promoted proliferation and migration of lung adenocarcinoma cells, accompanied by a significant increase in the expression of AQP5. These results indicate that NFAT5 plays important roles in proliferation and migration of human lung adenocarcinoma cells through regulating AQP5 expression, providing a new therapeutic option for lung adenocarcinoma therapy. - Highlights: • NFAT5 expression is higher in lung adenocarcinoma cells compared with normal cells. • NFAT5 knockdown decreases proliferation and migration of lung adenocarcinoma cells. • Knockdown of NFAT5 reduces AQP5 expression in human lung adenocarcinoma cells. • Overexpression of NFAT5 promotes proliferation and migration of lung adenocarcinoma cells. • Overexpression of NFAT5 increases AQP5 expression in human lung adenocarcinoma cells.

NFAT5 promotes proliferation and migration of lung adenocarcinoma cells in part through regulating AQP5 expression

International Nuclear Information System (INIS)

Guo, Kai; Jin, Faguang

2015-01-01

The osmoregulated transcription factor nuclear factor of activated T-cells 5(NFAT5), has been found to play important roles in the development of many kinds of human cancers, including breast cancer, colon carcinoma, renal cell carcinoma and melanoma. The aim of the present study was to determine whether NFAT5 is involved in the proliferation and migration of lung adenocarcinoma cells. We found that NFAT5 was upregulated in lung adenocarcinoma cells and knockdown of NFAT5 decreased proliferation and migration of the cells, accompanied by a significant reduction in the expression of AQP5. AQP5 was upregulated in lung adenocarcinoma cells and knockdown of AQP5 also inhibited proliferation and migration of the cells as knockdown of NFAT5 did. Moreover, overexpression of NFAT5 promoted proliferation and migration of lung adenocarcinoma cells, accompanied by a significant increase in the expression of AQP5. These results indicate that NFAT5 plays important roles in proliferation and migration of human lung adenocarcinoma cells through regulating AQP5 expression, providing a new therapeutic option for lung adenocarcinoma therapy. - Highlights: • NFAT5 expression is higher in lung adenocarcinoma cells compared with normal cells. • NFAT5 knockdown decreases proliferation and migration of lung adenocarcinoma cells. • Knockdown of NFAT5 reduces AQP5 expression in human lung adenocarcinoma cells. • Overexpression of NFAT5 promotes proliferation and migration of lung adenocarcinoma cells. • Overexpression of NFAT5 increases AQP5 expression in human lung adenocarcinoma cells

HER2 testing of gastro-oesophageal adenocarcinoma: a commentary and guidance document from the Association of Clinical Pathologists Molecular Pathology and Diagnostics Committee.

Science.gov (United States)

Wong, Newton A C S; Amary, Fernanda; Butler, Rachel; Byers, Richard; Gonzalez, David; Haynes, Harry R; Ilyas, Mohammad; Salto-Tellez, Manuel; Taniere, Philippe

2018-05-01

The use of biologics targeted to the human epidermal growth factor receptor 2 (HER2) protein is the latest addition to the armamentarium used to fight advanced gastric or gastro-oesophageal junction adenocarcinoma. The decision to treat with the biologic trastuzumab is completely dependent on HER2 testing of tumour tissue. In 2017, the College of American Pathologists, American Society for Clinical Pathology and the American Society of Clinical Oncology jointly published guidelines for HER2 testing and clinical decision making in gastro-oesophageal adenocarcinoma. The Association of Clinical Pathologists Molecular Pathology and Diagnostics Committee has issued the following document as a commentary of these guidelines and, in parallel, to provide guidance on HER2 testing in National Health Service pathology departments within the UK. This guidance covers issues related to case selection, preanalytical aspects, analysis and interpretation of such HER2 testing. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Advanced gastric adenocarcinoma. Influence of preoperative radiation therapy on toxicity and long-term survival rates

International Nuclear Information System (INIS)

Malzoni, Carlos Eduardo

1996-01-01

The surgical treatment of gastric cancer has better long-term survival rates when performed in patients with early gastric cancer. Worse results are obtained in treatment of advanced gastric cancer. Most patients in west centers are treated in advanced stages. A great number of them go through a surgical treatment unable by itself to cure them. the frequent local recurrence caused by failure of the surgical treatment has been keeping poor survival rates in patients with advanced gastric cancer for decades. The desire of improving survival is the reason of the use of adjuvant therapies. This paper achieved the retrospective study of the influence of preoperative radiation therapy (2000 cGy) in long-term survival rates (120 months) of patients with advanced gastric cancer on stages IIIa, IIIb and IV. The possible injuries caused in the liver and kidney were observed also as well as first group was treated by surgical and radiation therapies and the second received surgical treatment only. There was no statistical difference between the two groups when sex, age, race, occurrence of other diseases, nutritional assessment, TNM stage, occurrence of obstruction or bleeding caused by tumor, surgical procedure and hepatic and renal function were considered. Survival rates and changes on hepatic and renal function were statistically compared. The results showed a statistic improvement on the long-term survival rates of stage IIIa patients treated by preoperative radiation therapy. No statistic difference was observed on hepatic or renal function between the groups. No adverse influence of radiation therapy method was detected by the used parameters. There was no statistical difference between the two groups when immediate surgical complications were considered. (author)

Epstein-Barr virus-positive gastric cancer: a distinct molecular subtype of the disease?

Science.gov (United States)

Jácome, Alexandre Andrade Dos Anjos; Lima, Enaldo Melo de; Kazzi, Ana Izabela; Chaves, Gabriela Freitas; Mendonça, Diego Cavalheiro de; Maciel, Marina Mara; Santos, José Sebastião Dos

2016-04-01

Approximately 90% of the world population is infected by Epstein-Barr virus (EBV). Usually, it infects B lymphocytes, predisposing them to malignant transformation. Infection of epithelial cells occurs rarely, and it is estimated that about to 10% of gastric cancer patients harbor EBV in their malignant cells. Given that gastric cancer is the third leading cause of cancer-related mortality worldwide, with a global annual incidence of over 950,000 cases, EBV-positive gastric cancer is the largest group of EBV-associated malignancies. Based on gene expression profile studies, gastric cancer was recently categorized into four subtypes; EBV-positive, microsatellite unstable, genomically stable and chromosomal instability. Together with previous studies, this report provided a more detailed molecular characterization of gastric cancer, demonstrating that EBV-positive gastric cancer is a distinct molecular subtype of the disease, with unique genetic and epigenetic abnormalities, reflected in a specific phenotype. The recognition of characteristic molecular alterations in gastric cancer allows the identification of molecular pathways involved in cell proliferation and survival, with the potential to identify therapeutic targets. These findings highlight the enormous heterogeneity of gastric cancer, and the complex interplay between genetic and epigenetic alterations in the disease, and provide a roadmap to implementation of genome-guided personalized therapy in gastric cancer. The present review discusses the initial studies describing EBV-positive gastric cancer as a distinct clinical entity, presents recently described genetic and epigenetic alterations, and considers potential therapeutic insights derived from the recognition of this new molecular subtype of gastric adenocarcinoma.

Synchronous advanced gastric adenocarcinoma and advanced esophageal squamous cell carcinoma

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Fernando Augusto Mardiros Herbella

2002-01-01

Full Text Available CONTEXT: Synchronous associations of esophageal and gastric cancers are not a common finding, especially with differing histological types and both tumors in advanced forms. A case with such an association is presented, in which an unusual therapy was proposed: palliative gastrectomy and esophageal intubation. CASE REPORT: A 75-year-old white man was referred to our service complaining of malaise and weight loss for one year and dysphagia and vomiting for 2 months. The patient had sought out medical consultation as a result of the latter two complaints.

Radioimmunoimaging of nude mice bearing human lung adenocarcinoma xenografts after injecting 131I-McAbs

International Nuclear Information System (INIS)

Liu Liang

1992-01-01

Monoclonal antibodies (Lc86a-C5, Lc86a-H8) directed against human lung adenocarcinoma cell line LTEP-a-2 and normal BALB/c IgG were labelled with iodine-131 by chloramine T. The 131 I-McAbs and 131 I-IgG were respectively injected into the peritoneal cavities of nude mice bearing transplanted human lung adenocarcinoma cell line LTEP-a-2. After 72 h, the tumor tissue in nude mice injected with 131 I-McAbs was distinguishable from normal tissues as a very clear image obtained during gamma scintigraphy. No difference was found between tumor and normal tissues in the nude mice injected with 131 I-IgG. The tumor: blood ration was 3.1:1 in nude injected with 131 I McAb(H8) and 0.9:1 in nude mice injected with 131 I-IgG respectively. This indicates that the tumor tissue image was the result of specific binding of the 131 I-McAbs, which have high specificity and affinity both in vitro and in vivo, to tumor cells, and these monoclonal antibodies may serve as potential agents in tumor diagnosis and treatment

De novo gastric adenocarcinoma 1 year after sleeve gastrectomy in a transplant patient

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M. Masrur

2016-01-01

Conclusions: No direct relation has been established between sleeve gastrectomy and the development of gastric cancer. Robotic procedures allow for complex multiorgan resections, while preserving the benefits of minimally invasive surgery.

Restoration of tumor suppressor miR-34 inhibits human p53-mutant gastric cancer tumorspheres

International Nuclear Information System (INIS)

Ji, Qing; Hao, Xinbao; Meng, Yang; Zhang, Min; DeSano, Jeffrey; Fan, Daiming; Xu, Liang

2008-01-01

MicroRNAs (miRNAs), some of which function as oncogenes or tumor suppressor genes, are involved in carcinogenesis via regulating cell proliferation and/or cell death. MicroRNA miR-34 was recently found to be a direct target of p53, functioning downstream of the p53 pathway as a tumor suppressor. miR-34 targets Notch, HMGA2, and Bcl-2, genes involved in the self-renewal and survival of cancer stem cells. The role of miR-34 in gastric cancer has not been reported previously. In this study, we examined the effects of miR-34 restoration on p53-mutant human gastric cancer cells and potential target gene expression. Human gastric cancer cells were transfected with miR-34 mimics or infected with the lentiviral miR-34-MIF expression system, and validated by miR-34 reporter assay using Bcl-2 3'UTR reporter. Potential target gene expression was assessed by Western blot for proteins, and by quantitative real-time RT-PCR for mRNAs. The effects of miR-34 restoration were assessed by cell growth assay, cell cycle analysis, caspase-3 activation, and cytotoxicity assay, as well as by tumorsphere formation and growth. Human gastric cancer Kato III cells with miR-34 restoration reduced the expression of target genes Bcl-2, Notch, and HMGA2. Bcl-2 3'UTR reporter assay showed that the transfected miR-34s were functional and confirmed that Bcl-2 is a direct target of miR-34. Restoration of miR-34 chemosensitized Kato III cells with a high level of Bcl-2, but not MKN-45 cells with a low level of Bcl-2. miR-34 impaired cell growth, accumulated the cells in G1 phase, increased caspase-3 activation, and, more significantly, inhibited tumorsphere formation and growth. Our results demonstrate that in p53-deficient human gastric cancer cells, restoration of functional miR-34 inhibits cell growth and induces chemosensitization and apoptosis, indicating that miR-34 may restore p53 function. Restoration of miR-34 inhibits tumorsphere formation and growth, which is reported to be

Epstein-Barr Virus-Associated Lymphoepithelioma-Like Gastric Carcinoma Presenting as a Submucosal Mass: CT Findings with Pathologic Correlation

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Kim, Sang Won; Shin, Hyeong Cheol; Kim, Il Young; Kim, Chang Jin; Lee, Ji Hye; Lee, Chang Kyun; Jeong, Dong Jun [Soonchunhyang University Cheonan Hospital, Cheonan(Korea, Republic of)

2010-12-15

A lymphoepithelioma-like carcinoma, characterized by a carcinoma with heavy lymphocyte infiltration, is one of the histological patterns observed in patients with Epstein-Barr virus (EBV)-associated gastric carcinoma. Less than half of invasive carcinomas with lymphoepithelioma-like histology can grow to make a submucosal mass. These tumors generally have a better prognosis than conventional adenocarcinomas. We report a case of an EBV-associated lymphoepitheliomalike gastric carcinoma that presented as a submucosal mass on multi-detector (MD) CT and correlate them with the pathology

Epstein-Barr Virus-Associated Lymphoepithelioma-Like Gastric Carcinoma Presenting as a Submucosal Mass: CT Findings with Pathologic Correlation

International Nuclear Information System (INIS)

Kim, Sang Won; Shin, Hyeong Cheol; Kim, Il Young; Kim, Chang Jin; Lee, Ji Hye; Lee, Chang Kyun; Jeong, Dong Jun

2010-01-01

A lymphoepithelioma-like carcinoma, characterized by a carcinoma with heavy lymphocyte infiltration, is one of the histological patterns observed in patients with Epstein-Barr virus (EBV)-associated gastric carcinoma. Less than half of invasive carcinomas with lymphoepithelioma-like histology can grow to make a submucosal mass. These tumors generally have a better prognosis than conventional adenocarcinomas. We report a case of an EBV-associated lymphoepitheliomalike gastric carcinoma that presented as a submucosal mass on multi-detector (MD) CT and correlate them with the pathology

Effect of intravenous infusion of glyceryl trinitrate on gastric and small intestinal motor function in healthy humans

DEFF Research Database (Denmark)

Madsen, Jan Lysgård; Fuglsang, Stefan; Graff, J

2006-01-01

: To examine the effect of intravenous infusion of glyceryl trinitrate on gastric and small intestinal motor function after a meal in healthy humans. METHODS: Nine healthy volunteers participated in a placebo-controlled, double-blind, crossover study. Each volunteer was examined during intravenous infusion...... of glyceryl trinitrate 1 microg/kg x min or saline. A gamma camera technique was used to measure gastric emptying and small intestinal transit after a 1600-kJ mixed liquid and solid meal. Furthermore, duodenal motility was assessed by manometry. RESULTS: Glyceryl trinitrate did not change gastric mean...... emptying time, gastric half emptying time, gastric retention at 15 min or small intestinal mean transit time. Glyceryl trinitrate did not influence the frequency of duodenal contractions, the amplitude of duodenal contractions or the duodenal motility index. CONCLUSIONS: Intravenous infusion of glyceryl...

Genomic dysregulation in gastric tumors.

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Janjigian, Yelena Y; Kelsen, David P

2013-03-01

Gastric cancer is among the most common human malignancies and the second leading cause of cancer-related death. The different epidemiologic and histopathology of subtypes of gastric cancer are associated with different genomic patterns. Data suggests that gene expression patterns of proximal, distal gastric cancers-intestinal type, and diffuse/signet cell are well separated. This review summarizes the genetic and epigenetic changes thought to drive gastric cancer and the emerging paradigm of gastric cancer as three unique disease subtypes. Copyright © 2012 Wiley Periodicals, Inc.

Nonsense and missense mutation of mitochondrial ND6 gene promotes cell migration and invasion in human lung adenocarcinoma

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Yuan, Yang; Wang, Weixing; Li, Huizhong; Yu, Yongwei; Tao, Jin; Huang, Shengdong; Zeng, Zhiyong

2015-01-01

Previous study showed that mitochondrial ND6 (mitND6) gene missense mutation resulted in NADH dehydrogenase deficiency and was associated with tumor metastasis in several mouse tumor cell lines. In the present study, we investigated the possible role of mitND6 gene nonsense and missense mutations in the metastasis of human lung adenocarcinoma. The presence of mitND6 gene mutations was screened by DNA sequencing of tumor tissues from 87 primary lung adenocarcinoma patients and the correlation of the mutations with the clinical features was analyzed. In addition, we constructed cytoplasmic hybrid cells with denucleared primary lung adenocarcinoma cell as the mitochondria donor and mitochondria depleted lung adenocarcinoma A549 cell as the nuclear donor. Using these cells, we studied the effects of mitND6 gene nonsense and missense mutations on cell migration and invasion through wounding healing and matrigel-coated transwell assay. The effects of mitND6 gene mutations on NADH dehydrogenase activity and ROS production were analyzed by spectrophotometry and flow cytometry. mitND6 gene nonsense and missense mutations were detected in 11 of 87 lung adenocarcinoma specimens and was correlated with the clinical features including age, pathological grade, tumor stage, lymph node metastasis and survival rate. Moreover, A549 cell containing mitND6 gene nonsense and missense mutation exhibited significantly lower activity of NADH dehydrogenase, higher level of ROS, higher capacity of cell migration and invasion, and higher pAKT and pERK1/ERK2 expression level than cells with the wild type mitND6 gene. In addition, NADH dehydrogenase inhibitor rotenone was found to significantly promote the migration and invasion of A549 cells. Our data suggest that mitND6 gene nonsense and missense mutation might promote cell migration and invasion in lung adenocarcinoma, probably by NADH dehydrogenase deficiency induced over-production of ROS

Origin of adenocarcinoma in Barrett's esophagus: P53 and Ki67 expression and histopathologic background Origem do adenocarcinoma no esôfago de Barrett: bases histopathológicas e expressão dos genes p53 e Ki67

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Sergio Szachnowicz

2005-04-01

Full Text Available Barrett's esophagus is the substitution of squamous epithelium of the distal esophagus by columnar epithelium. Intestinal metaplasia in Barrett's esophagus is considered to be the main risk factor for the development of adenocarcinoma. Diffuse adenocarcinoma and Barrett's esophagus without intestinal metaplasia are rare, and reports on the subject are scarce. PURPOSE AND METHOD: To estimate the prevalence of adenocarcinoma in 297 patients with Barrett's esophagus, during the period of 1990 to 2002, and in 13 patients undergoing surgery, to conduct detailed macroscopic and microscopic analysis, with performance of immunohistochemical tests for p53 and Ki67, correlating the type of tumor with its adjacent epithelium. RESULTS: In our patients with Barrett's esophagus, there was a prevalence of 5.7% of adenocarcinoma. The tumors developed only when the Barrett's esophagus segment was long (>3.0 cm. Tumors were located close to the squamous-columnar junction. The histological study revealed 2 patients (15.4% with Barrett's esophagus adjacent to a tumor with gastric metaplasia without the presence of intestinal metaplasia. Tumors were classified according to Nakamura's classification (23% differentiated pattern, and 77% undifferentiated pattern and to Lauren's classification (61% intestinal and 39% diffuse. The difference is due to the migration of microtubular and foveolar tumors of undifferentiated (gastric pattern in Nakamuras classification to the Lauren's intestinal type. The immunohistochemical test for Ki67 was strongly positive in all the patients, thus evidencing intense cell proliferation in both the columnar epithelium and tumor. Expression of p53 was negative in 67% of the adjacent columnar epithelia and 42% of the tumors, without any correlation between the tissue types. CONCLUSION: Adenocarcinoma develops from mixed columnar epithelium, either intestinal or gastric, showing both the gastric and the intestinal patterns; thus, tumors can

Inhibitory effects of 3-bromopyruvate on human gastric cancer implant tumors in nude mice.

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Xian, Shu-Lin; Cao, Wei; Zhang, Xiao-Dong; Lu, Yun-Fei

2014-01-01

Gastric cancer is a common malignant tumor. Our previous study demonstrated inhibitory effects of 3-bromopyruvate (3-BrPA) on pleural mesothelioma. Moreover, we found that 3-BrPA could inhibit human gastric cancer cell line SGC-7901 proliferation in vitro, but whether similar effects might be exerted in vivo have remained unclear. To investigate the effect of 3-BrPA to human gastric cancer implant tumors in nude mice. Animals were randomly divided into 6 groups: 3-BrPA low, medium and high dose groups, PBS negative control group 1 (PH7.4), control group 2 (PH 6.8-7.8) and positive control group receiving 5-FU. The TUNEL method was used to detect apoptosis, and cell morphology and structural changes of tumor tissue were observed under transmission electron microscopy (TEM). 3-BrPA low, medium, high dose group, and 5-FU group, the tumor volume inhibition rates were 34.5%, 40.2%, 45.1%, 47.3%, tumor volume of experimental group compared with 2 PBS groups (p0.05). TEM showed typical characteristics of apoptosis. TUNEL demonstrated apoptosis indices of 28.7%, 39.7%, 48.7% for the 3-BrPA low, medium, high dose groups, 42.2% for the 5-FU group and 5% and 4.3% for the PBS1 (PH7.4) and PBS2 (PH6.8-7.8) groups. Compared each experimental group with 2 negative control groups, there was significant difference (p0.05), but there was between the 5-FU and high dose groups (p<0.05). This study indicated that 3-BrPA in vivo has strong inhibitory effects on human gastric cancer implant tumors in nude mice .

Mechanistic understanding of time-dependent oral absorption based on gastric motor activity in humans.

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Higaki, Kazutaka; Choe, Sally Y; Löbenberg, Raimar; Welage, Lynda S; Amidon, Gordon L

2008-09-01

The relationship of gastric motor activity and gastric emptying of 0.7 mm caffeine pellets with their absorption was investigated in the fed state in healthy human subjects by simultaneous monitoring of antral motility and plasma concentrations. A kinetic model for gastric emptying-dependent absorption yielded multiple phases of gastric emptying and rate constants (k(g)) with large inter-individual differences and large variability in onset of gastric emptying (50-175 min). The model suggests that 50% of the dose is emptied in 1-2h and over 90% emptied by 3.5h following dosing, in all subjects. The maximum values of k(g) (k(g)(max)) were much greater than those reported for emptying of liquids in the fasted state and were comparable to k(g) values in the late Phase II/III of the migrating motor complex (MMC). The model described the observed irregular absorption rate-time and plasma concentration-time profiles adequately but not in detail. The model was more successful at simulating double-peak phenomena in absorption rate profiles and onset of caffeine absorption. The results suggest that gastric emptying regulates drug absorption of small particles in the fed state. Further, estimates of k(a) derived using the time-dependent absorption model were closer to the intrinsic absorption rate constant for caffeine.

Gastric cancer-derived MSC-secreted PDGF-DD promotes gastric cancer progression.

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Huang, Feng; Wang, Mei; Yang, Tingting; Cai, Jie; Zhang, Qiang; Sun, Zixuan; Wu, Xiaodan; Zhang, Xu; Zhu, Wei; Qian, Hui; Xu, Wenrong

2014-11-01

This study was designed to investigate the role of PDGF-DD secreted by gastric cancer-derived mesenchymal stem cells (GC-MSCs) in human gastric cancer progression. Gastric cancer cells were indirectly co-cultured with GC-MSCs in a transwell system. The growth and migration of gastric cancer cells were evaluated by cell colony formation assay and transwell migration assay, respectively. The production of PDGF-DD in GC-MSCs was determined by using Luminex and ELISA. Neutralization of PDGFR-β by su16f and siRNA interference of PDGF-DD in GC-MSCs was used to demonstrate the role of PDGF-DD produced by GC-MSCs in gastric cancer progression. GC-MSC conditioned medium promoted gastric cancer cell proliferation and migration in vitro and in vivo. Co-culture with GC-MSCs increased the phosphorylation of PDGFR-β in SGC-7901 cells. Neutralization of PDGFR-β by su16f blocked the promoting role of GC-MSC conditioned medium in gastric cancer cell proliferation and migration. Recombinant PDGF-DD duplicated the effects of GC-MSC conditioned medium on gastric cancer cells. Knockdown of PDGF-DD in GC-MSCs abolished its effects on gastric cancer cells in vitro and in vivo. PDGF-DD secreted by GC-MSCs is capable of promoting gastric cancer cell progression in vitro and in vivo. Targeting the PDGF-DD/PDGFR-β interaction between MSCs and gastric cancer cells may represent a novel strategy for gastric cancer therapy.

Diversity of the Gastric Microbiota in Thoroughbred Racehorses Having Gastric Ulcer.

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Dong, Hee-Jin; Ho, Hungwui; Hwang, Hyeshin; Kim, Yongbaek; Han, Janet; Lee, Inhyung; Cho, Seongbeom

2016-04-28

Equine gastric ulcer syndrome is one of the most frequently reported diseases in thoroughbred racehorses. Although several risk factors for the development of gastric ulcers have been widely studied, investigation of microbiological factors has been limited. In this study, the presence of Helicobacter spp. and the gastric microbial communities of thoroughbred racehorses having mild to severe gastric ulcers were investigated. Although Helicobacter spp. were not detected using culture and PCR techniques from 52 gastric biopsies and 52 fecal samples, the genomic sequences of H. pylori and H. ganmani were detected using nextgeneration sequencing techniques from 2 out of 10 representative gastric samples. The gastric microbiota of horses was mainly composed of Firmicutes (50.0%), Proteobacteria (18.7%), Bacteroidetes (14.4%), and Actinobacteria (9.7%), but the proportion of each phylum varied among samples. There was no major difference in microbial composition among samples having mild to severe gastric ulcers. Using phylogenetic analysis, three distinct clusters were observed, and one cluster differed from the other two clusters in the frequency of feeding, amount of water consumption, and type of bedding. To the best of our knowledge, this is the first study to investigate the gastric microbiota of thoroughbred racehorses having gastric ulcer and to evaluate the microbial diversity in relation to the severity of gastric ulcer and management factors. This study is important for further exploration of the gastric microbiota in racehorses and is ultimately applicable to improving animal and human health.

Enhancement of radiosensitivity of recombinant Ad-p53 gene on human lung adenocarcinoma cell with different p53 status

International Nuclear Information System (INIS)

Pang Dequan; Wang Peiguo; Wang Ping; Zhang Weiming

2008-01-01

Objective: To investigate the enhancement of radiosensitivity of recombinant Ad-p53 gene on human lung adenocarcinoma cell lines(A549 and GLC-82) with different p53 status in vitro. Methods: Two human lung adenocarcinoma cell lines of A549 and GLC-82 were examined on their difference in p53 status with immunohistochemistry stain and PCR-SSCP technique. Expand Ad-wtp53 was transfected into tumor cells. Clonogenic assays were performed to evaluate the inhibition effect on cell growth and the degree of sensitization to irradiation. Apoptosis and cell cycle changes were determined using the flow cytometry assay. Results: The A549 cell line presented positive P53 expression while GLC-82 negative. GLC-82 bore mutant p53 on the exon 7. The wtp53 gene could be efficiently expressed in the two cell lines and greatly inhibit the cell growth. Its efficiency didn't depend on the intrinsic p53 genetic status. After irradiation, its function of inducing G 1 arrest and apoptosis on GLC-82 cell line was much stronger than the A549 cell line. In both the A549 and GLC-82 cell lines, the combination of Ad-p53 plus radiation resulted in more apoptosis than the others. There was no significant difference between two groups. Conclusions: Ad-p53 can depress the tumor growth and enhance the radiosensitivity of human lung adenocarcinoma cells. And this effect is independent of endogenous p53 status. (authors)

Enhanced M1 macrophage polarization in human helicobacter pylori-associated atrophic gastritis and in vaccinated mice.

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Marianne Quiding-Järbrink

Full Text Available BACKGROUND: Infection with Helicobacter pylori triggers a chronic gastric inflammation that can progress to atrophy and gastric adenocarcinoma. Polarization of macrophages is a characteristic of both cancer and infection, and may promote progression or resolution of disease. However, the role of macrophages and their polarization during H. pylori infection has not been well defined. METHODOLOGY/PRINCIPAL FINDINGS: By using a mouse model of infection and gastric biopsies from 29 individuals, we have analyzed macrophage recruitment and polarization during H. pylori infection by flow cytometry and real-time PCR. We found a sequential recruitment of neutrophils, eosinophils and macrophages to the gastric mucosa of infected mice. Gene expression analysis of stomach tissue and sorted macrophages revealed that gastric macrophages were polarized to M1 after H. pylori infection, and this process was substantially accelerated by prior vaccination. Human H. pylori infection was characterized by a mixed M1/M2 polarization of macrophages. However, in H. pylori-associated atrophic gastritis, the expression of inducible nitric oxide synthase was markedly increased compared to uncomplicated gastritis, indicative of an enhanced M1 macrophage polarization in this pre-malignant lesion. CONCLUSIONS/SIGNIFICANCE: These results show that vaccination of mice against H. pylori amplifies M1 polarization of gastric macrophages, and that a similar enhanced M1 polarization is present in human H. pylori-induced atrophic gastritis.

In vitro expansion of human gastric epithelial stem cells and their responses to bacterial infection

NARCIS (Netherlands)

Bartfeld, Sina; Bayram, Tülay; van de Wetering, Marc; Huch, Meritxell; Begthel, Harry; Kujala, Pekka; Vries, Robert; Peters, Peter J; Clevers, Hans

BACKGROUND & AIMS: We previously established long-term, 3-dimensional culture of organoids from mouse tissues (intestine, stomach, pancreas, and liver) and human intestine and pancreas. Here we describe conditions required for long-term 3-dimensional culture of human gastric stem cells. The

Metastatic Colonic Adenocarcinoma in Breast: Report of Two Cases and Review of the Literature

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Jiten P. Kothadia

2015-01-01

Full Text Available Metastatic adenocarcinoma to the breast from an extramammary site is extremely rare. In the literature, the most current estimate is that extramammary metastases account for only 0.43% of all breast malignancies and that, of these extramammary sites, colon cancer metastases form a very small subset. Most commonly seen metastasis in breast is from a contralateral breast carcinoma, followed by metastasis from hematopoietic neoplasms, malignant melanoma, sarcoma, lung, prostate, and ovary and gastric neoplasms. Here we present two rare cases, in which colonic adenocarcinomas were found to metastasize to the breast. In both cases, core biopsies were obtained from the suspicious areas identified on mammogram. Histopathology revealed neoplastic proliferation of atypical glandular components within benign breast parenchyma which were morphologically consistent with metastatic adenocarcinoma. By immunohistochemical staining, it was confirmed that the neoplastic components were immunoreactive to colonic markers and nonreactive to breast markers, thus further supporting the morphologic findings. It is extremely important to make this distinction between primary breast cancer and a metastatic process, in order to provide the most effective and appropriate treatment for the patient and to avoid any harmful or unnecessary surgical procedures.

Impact of MUC1 mucin downregulation in the phenotypic characteristics of MKN45 gastric carcinoma cell line.

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Natália R Costa

Full Text Available BACKGROUND: Gastric carcinoma is the second leading cause of cancer-associated death worldwide. The high mortality associated with this disease is in part due to limited knowledge about gastric carcinogenesis and a lack of available therapeutic and prevention strategies. MUC1 is a high molecular weight transmembrane mucin protein expressed at the apical surface of most glandular epithelial cells and a major component of the mucus layer above gastric mucosa. Overexpression of MUC1 is found in approximately 95% of human adenocarcinomas, where it is associated with oncogenic activity. The role of MUC1 in gastric cancer progression remains to be clarified. METHODOLOGY: We downregulated MUC1 expression in a gastric carcinoma cell line by RNA interference and studied the effects on cellular proliferation (MTT assay, apoptosis (TUNEL assay, migration (migration assay, invasion (invasion assay and aggregation (aggregation assay. Global gene expression was evaluated by microarray analysis to identify alterations that are regulated by MUC1 expression. In vivo assays were also performed in mice, in order to study the tumorigenicity of cells with and without MUC1 downregulation in MKN45 gastric carcinoma cell line. RESULTS: Downregulation of MUC1 expression increased proliferation and apoptosis as compared to controls, whereas cell-cell aggregation was decreased. No significant differences were found in terms of migration and invasion between the downregulated clones and the controls. Expression of TCN1, KLK6, ADAM29, LGAL4, TSPAN8 and SHPS-1 was found to be significantly different between MUC1 downregulated clones and the control cells. In vivo assays have shown that mice injected with MUC1 downregulated cells develop smaller tumours when compared to mice injected with the control cells. CONCLUSIONS: These results indicate that MUC1 downregulation alters the phenotype and tumorigenicity of MKN45 gastric carcinoma cells and also the expression of several

Helicobacter pylori Infection Causes Characteristic DNA Damage Patterns in Human Cells

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Max Koeppel

2015-06-01

Full Text Available Infection with the human pathogen Helicobacter pylori (H. pylori is a major risk factor for gastric cancer. Since the bacterium exerts multiple genotoxic effects, we examined the circumstances of DNA damage accumulation and identified regions within the host genome with high susceptibility to H. pylori-induced damage. Infection impaired several DNA repair factors, the extent of which depends on a functional cagPAI. This leads to accumulation of a unique DNA damage pattern, preferentially in transcribed regions and proximal to telomeres, in both gastric cell lines and primary gastric epithelial cells. The observed pattern correlates with focal amplifications in adenocarcinomas of the stomach and partly overlaps with known cancer genes. We thus demonstrate an impact of a bacterial infection directed toward specific host genomic regions and describe underlying characteristics that make such regions more likely to acquire heritable changes during infection, which could contribute to cellular transformation.

Role of the Wnt/β-catenin pathway in gastric cancer: An in-depth literature review

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Chiurillo, Miguel Angel

2015-01-01

Gastric cancer remains one of the most common cancers worldwide and one of the leading cause for cancer-related deaths. Gastric adenocarcinoma is a multifactorial disease that is genetically, cytologically and architecturally more heterogeneous than other gastrointestinal carcinomas. The aberrant activation of the Wnt/β-catenin signaling pathway is involved in the development and progression of a significant proportion of gastric cancer cases. This review focuses on the participation of the Wnt/β-catenin pathway in gastric cancer by offering an analysis of the relevant literature published in this field. Indeed, it is discussed the role of key factors in Wnt/β-catenin signaling and their downstream effectors regulating processes involved in tumor initiation, tumor growth, metastasis and resistance to therapy. Available data indicate that constitutive Wnt signalling resulting from Helicobacter pylori infection and inactivation of Wnt inhibitors (mainly by inactivating mutations and promoter hypermethylation) play an important role in gastric cancer. Moreover, a number of recent studies confirmed CTNNB1 and APC as driver genes in gastric cancer. The identification of specific membrane, intracellular, and extracellular components of the Wnt pathway has revealed potential targets for gastric cancer therapy. High-throughput “omics” approaches will help in the search for Wnt pathway antagonist in the near future. PMID:25992323

Gastric pyloric gland adenoma: a multicentre clinicopathological study of 67 cases.

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Choi, Won-Tak; Brown, Ian; Ushiku, Tetsuo; Yozu, Masato; Setia, Namrata; Srivastava, Amitabh; Johncilla, Melanie; Pai, Rish K; Gill, Ryan M; Fukayama, Masashi; Misdraji, Joseph; Lauwers, Gregory Y

2018-05-01

There is limited information regarding the clinicopathological and immunohistochemical characteristics of gastric pyloric gland adenomas (PGAs). Sixty-seven cases of gastric PGA from 57 patients were analysed. PGAs occurred with similar frequency in men and women (47.4 and 52.6%, respectively), with a mean age of 66 years. Most presented in the gastric body/fundus (67.2%). Fifteen cases (22.4%) developed against a background of autoimmune gastritis (AIG), whereas normal mucosa was seen in 35.8%. Only 16.4% (11 cases) developed in patients with a genetic predisposition, most commonly familial adenomatous polyposis. Low-grade lesions had a mean size of 1.5 cm, while PGAs with high-grade dysplasia (HGD) or adenocarcinoma had a mean size of 3.5 cm (P < 0.001) and more commonly showed tubulovillous architecture (50.0 versus 25.6% in low-grade dysplasia; P = 0.040). Most PGAs (61.2%) co-expressed mucin (MUC)5AC and MUC6 (mixed type), which was associated significantly with HGD or adenocarcinoma (P = 0.013). AIG was also associated with HGD (P = 0.027), but genetic predisposition did not correlate with the grade of dysplasia (P = 0.793). The recurrence rate of PGA was similar for high- (11.8%) and low-grade lesions (7.4%) (P = 0.624). The risk of HGD increases with the size of PGA, tubulovillous architecture and the presence of AIG as well as mixed immunophenotype. As the overall local recurrence rate is less than 10%, PGAs may be treated conservatively, but they should be excised completely if possible, particularly if they are large or show high-grade features. © 2017 John Wiley & Sons Ltd.

BITC Sensitizes Pancreatic Adenocarcinomas to TRAIL-induced Apoptosis

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Christina A. Wicker

2009-01-01

Full Text Available Pancreatic adenocarcinoma is an aggressive cancer with a greater than 95% mortality rate and short survival after diagnosis. Chemotherapeutic resistance hinders successful treatment. This resistance is often associated with mutations in codon 12 of the K-Ras gene (K-Ras 12, which is present in over 90% of all pancreatic adenocarcinomas. Codon 12 mutations maintain Ras in a constitutively active state leading to continuous cellular proliferation. Our study determined if TRAIL resistance in pancreatic adenocarcinomas with K-Ras 12 mutations could be overcome by first sensitizing the cells with Benzyl isothiocyanate (BITC. BITC is a component of cruciferous vegetables and a cell cycle inhibitor. BxPC3, MiaPaCa2 and Panc-1 human pancreatic adenocarcinoma cell lines were examined for TRAIL resistance. Our studies show BITC induced TRAIL sensitization by dual activation of both the extrinsic and intrinsic apoptotic pathways.

Growth inhibitory effect of 4-phenyl butyric acid on human gastric cancer cells is associated with cell cycle arrest.

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Li, Long-Zhu; Deng, Hong-Xia; Lou, Wen-Zhu; Sun, Xue-Yan; Song, Meng-Wan; Tao, Jing; Xiao, Bing-Xiu; Guo, Jun-Ming

2012-01-07

To investigate the growth effects of 4-phenyl butyric acid (PBA) on human gastric carcinoma cells and their mechanisms. Moderately-differentiated human gastric carcinoma SGC-7901 and lowly-differentiated MGC-803 cells were treated with 5, 10, 20, 40, and 60 μmol/L PBA for 1-4 d. Cell proliferation was detected using the MTT colorimetric assay. Cell cycle distributions were examined using flow cytometry. The proliferation of gastric carcinoma cells was inhibited by PBA in a dose- and time-dependent fashion. Flow cytometry showed that SGC-7901 cells treated with low concentrations of PBA were arrested at the G₀/G₁ phase, whereas cells treated with high concentrations of PBA were arrested at the G₂/M phase. Although MGC-803 cells treated with low concentrations of PBA were also arrested at the G₀/ G₁ phase, cells treated with high concentrations of PBA were arrested at the S phase. The growth inhibitory effect of PBA on gastric cancer cells is associated with alteration of the cell cycle. For moderately-differentiated gastric cancer cells, the cell cycle was arrested at the G₀ /G₁ and G₂/M phases. For lowly-differentiated gastric cancer cells, the cell cycle was arrested at the G₀/G₁ and S phases.

Menetriere's disease associated with gastric adenocarcinoma in a child: imaging aspect

International Nuclear Information System (INIS)

Silva, Pedro Henrique Ramos Quintino da; Batista, Renan Pedroso; Rigo, Paula; Toma, Ricardo Katsuya; Oliveira, Luiz Antonio Nunes de; Suzuki, Lisa

2016-01-01

Female patient aged 18 years and 8 months, with diagnosis of hypertrophic gastritis since the age of 10, when she started having sporadic vomiting, weight loss, and anemia (Hb = 5.0 at diagnosis in August 2007). On her first upper gastrointestinal endoscopy (UGE) performed at the Instituto da Crianca (ICr) at HC-FMUSP, in August 2007, it was seem globally hypertrophied and swollen gastric mucosa, with an infiltrative lesion with ill-defined margins. A biopsy confirmed hyperplastic gastritis with a pattern of Menetrier's disease. Outpatient follow-up was initiated at Pediatric Gastroenterology Service of ICr in January 2008, with periodic clinical evaluation and UGE. The patient progressed in the following months with poor appetite and episodes of upper gastrointestinal bleeding and melena, requiring hospitalization in the city of origin and transfusions of blood concentrates. In the following years, she showed less recurrent episodes of bleeding than as seen in the first years after diagnosis, but continued undergoing serial UGEs for disease control and malignant surveillance, maintaining the same macroscopic and microscopic pattern. The patient has been submitted to extensive research for Helicobacter pylori in gastric biopsies, all with negative results, the same occurring with immunophenotyping for cytomegalovirus (CMV). Clinically, she continued to show poor weight gain, but with proper growth and no generalized edema at any time. (author)

A comparison of Helicobacter pylori and non-Helicobacter pylori Helicobacter spp. Binding to canine gastric mucosa with defined gastric glycophenotype.

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Amorim, Irina; Freitas, Daniela P; Magalhães, Ana; Faria, Fátima; Lopes, Célia; Faustino, Augusto M; Smet, Annemieke; Haesebrouck, Freddy; Reis, Celso A; Gärtner, Fátima

2014-08-01

The gastric mucosa of dogs is often colonized by non-Helicobacter pylori helicobacters (NHPH), while H. pylori is the predominant gastric Helicobacter species in humans. The colonization of the human gastric mucosa by H. pylori is highly dependent on the recognition of host glycan receptors. Our goal was to define the canine gastric mucosa glycophenotype and to evaluate the capacity of different gastric Helicobacter species to adhere to the canine gastric mucosa. The glycosylation profile in body and antral compartments of the canine gastric mucosa, with focus on the expression of histo-blood group antigens was evaluated. The in vitro binding capacity of FITC-labeled H. pylori and NHPH to the canine gastric mucosa was assessed in cases representative of the canine glycosylation pattern. The canine gastric mucosa lacks expression of type 1 Lewis antigens and presents a broad expression of type 2 structures and A antigen, both in the surface and glandular epithelium. Regarding the canine antral mucosa, H. heilmannii s.s. presented the highest adhesion score whereas in the body region the SabA-positive H. pylori strain was the strain that adhered more. The canine gastric mucosa showed a glycosylation profile different from the human gastric mucosa suggesting that alternative glycan receptors may be involved in Helicobacter spp. binding. Helicobacter pylori and NHPH strains differ in their ability to adhere to canine gastric mucosa. Among the NHPH, H. heilmannii s.s. presented the highest adhesion capacity in agreement with its reported colonization of the canine stomach. © 2014 John Wiley & Sons Ltd.

Evaluation of PET and laparoscopy in STagIng advanced gastric cancer: a multicenter prospective study (PLASTIC-study).

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Brenkman, H J F; Gertsen, E C; Vegt, E; van Hillegersberg, R; van Berge Henegouwen, M I; Gisbertz, S S; Luyer, M D P; Nieuwenhuijzen, G A P; van Lanschot, J J B; Lagarde, S M; de Steur, W O; Hartgrink, H H; Stoot, J H M B; Hulsewe, K W E; Spillenaar Bilgen, E J; van Det, M J; Kouwenhoven, E A; van der Peet, D L; Daams, F; van Sandick, J W; van Grieken, N C T; Heisterkamp, J; van Etten, B; Haveman, J W; Pierie, J P; Jonker, F; Thijssen, A Y; Belt, E J T; van Duijvendijk, P; Wassenaar, E; van Laarhoven, H W M; Wessels, F J; Haj Mohammad, N; van Stel, H F; Frederix, G W J; Siersema, P D; Ruurda, J P

2018-04-20

Initial staging of gastric cancer consists of computed tomography (CT) and gastroscopy. In locally advanced (cT3-4) gastric cancer, fluorodeoxyglucose positron emission tomography with CT (FDG-PET/CT or PET) and staging laparoscopy (SL) may have a role in staging, but evidence is scarce. The aim of this study is to evaluate the impact and cost-effectiveness of PET and SL in addition to initial staging in patients with locally advanced gastric cancer. This prospective observational cohort study will include all patients with a surgically resectable, advanced gastric adenocarcinoma (cT3-4b, N0-3, M0), that are scheduled for treatment with curative intent after initial staging with gastroscopy and CT. The modalities to be investigated in this study is the addition of PET and SL. The primary outcome of this study is the proportion of patients in whom the PET or SL lead to a change in treatment strategy. Secondary outcome parameters are: diagnostic performance, morbidity and mortality, quality of life, and cost-effectiveness of these additional diagnostic modalities. The study recently started in August 2017 with a duration of 36 months. At least 239 patients need to be included in this study to demonstrate that the diagnostic modalities are break-even. Based on the annual number of gastrectomies in the participating centers, it is estimated that approximately 543 patients are included in this study. In this study, it is hypothesized that performing PET and SL for locally advanced gastric adenocarcinomas results in a change of treatment strategy in 27% of patients and an annual cost-reduction in the Netherlands of €916.438 in this patient group by reducing futile treatment. The results of this study may be applicable to all countries with comparable treatment algorithms and health care systems. NCT03208621 . This trial was registered prospectively on June 30, 2017.

Review article: the investigation and management of gastric neuroendocrine tumours.

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Basuroy, R; Srirajaskanthan, R; Prachalias, A; Quaglia, A; Ramage, J K

2014-05-01

Gastric carcinoids (GCs) or neuroendocrine tumours (NETs) are increasingly identified at endoscopy, and account for 0.6-2% of all gastric polyps identified. The SEER database in the US has demonstrated a rising incidence of gastric NETs amongst all NETs; from 2.2% between 1950 and 1969 to 6.0% between 2000 and 2007. To review the literature and assist clinicians in managing patients with GCs. A literature search was conducted through MEDLINE using search terms: gastric, carcinoid, neuroendocrine tumour, therapy, endoscopy, mucosal resection, submucosal dissection. Relevant articles were identified through manual review. The reference lists of these articles were reviewed to include further appropriate articles. There are three types of GCs with important epidemiological, pathophysiological, histological and endoscopic differences that affect prognosis and management. Type 1 and 2 GCs develop in the context of hypergastrinaemia that originates from achlorhydria in atrophic gastritis and a gastrinoma, respectively. Type 3 GCs occur sporadically and independent of gastrin. The histological type, grade and Ki67 index are used to determine prognosis and direct clinical management. Type 1 GCs >1 cm in size and type 2 GCs should be assessed for invasion beyond the submucosa with EUS prior to endoscopic resection with EMR or ESD. Type 3 GCs should be managed as per recommendations for gastric adenocarcinoma. The treatment of advanced disease is multimodal. Patients with gastric carcinoids should be discussed in a specialist neuroendocrine tumour multidisciplinary meeting to ensure all treatment options are explored in localised and advanced disease. Areas of controversy exist that need further research. © 2014 John Wiley & Sons Ltd.

Lack of effect of synthetic human gastric inhibitory polypeptide and glucagon-like peptide 1 [7-36 amide] infused at near-physiological concentrations on pentagastrin-stimulated gastric acid secretion in normal human subjects

DEFF Research Database (Denmark)

Nauck, M A; Bartels, E; Orskov, C

1992-01-01

-stimulated (0.1 micrograms/kg/h from -90 to 120 min) gastric volume, acid and chloride output, on separate occasions, synthetic human GIP (1 pmol/kg/min) and/or GLP-1 [7-36 amide] (0.3 pmol/kg/min) or placebo (0.9% NaCl with 1% albumin) were infused intravenously (from -30 to 120 min) in 9 healthy volunteers...... secretion). In conclusion, (penta)gastrin-stimulated gastric acid secretion is not inhibited by physiological circulating concentrations of GIP or GLP-1 [7-36 amide]. Therefore, the insulinotropic action of these intestinal hormones is physiologically more important than their possible role...

Pathobiology of Helicobacter pylori-induced Gastric Cancer

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Amieva, Manuel; Peek, Richard M.

2015-01-01

Colonization of the human stomach by Helicobacter pylori and its role in causing gastric cancer is one of the richest examples of complex relationship among human cells, microbes, and their environment. It is also a puzzle of enormous medical importance given the incidence and lethality of gastric cancer worldwide. We review recent findings that have changed how we view these relationships and affected the direction of gastric cancer research. For example, recent data indicate that subtle mismatches between host and microbe genetic traits greatly affect risk of gastric cancer. The ability of H pylori and its oncoprotein CagA to reprogram epithelial cells and activate properties of stemness demonstrates the sophisticated relationship among H pylori and progenitor cells in the gastric mucosa. The observation that cell-associated H pylori can colonize the gastric glands and directly affect precursor and stem cells supports these observations. The ability to mimic these interactions in human gastric organoid cultures as well as animal models will allow investigators to more fully unravel the extent of H pylori control on the renewing gastric epithelium. Finally, our realization that external environmental factors, such as dietary components and essential micronutrients, as well as the gastrointestinal microbiota, can change the balance between H pylori’s activity as a commensal or a pathogen has provided direction to studies aimed at defining the full carcinogenic potential of this organism. PMID:26385073

Reduction of hexavalent chromium by fasted and fed human gastric fluid. I. Chemical reduction and mitigation of mutagenicity

Energy Technology Data Exchange (ETDEWEB)

De Flora, Silvio, E-mail: sdf@unige.it [Department of Health Sciences, University of Genoa, 16132 Genoa (Italy); Camoirano, Anna, E-mail: Anna.Fiorenza.Camoirano@unige.it [Department of Health Sciences, University of Genoa, 16132 Genoa (Italy); Micale, Rosanna T., E-mail: rosannamicale@yahoo.it [Department of Health Sciences, University of Genoa, 16132 Genoa (Italy); La Maestra, Sebastiano, E-mail: lamaestra78@yahoo.it [Department of Health Sciences, University of Genoa, 16132 Genoa (Italy); Savarino, Vincenzo, E-mail: vsavarin@unige.it [Gastroenterology Unit, Department of Internal Medicine, University of Genoa, 16132 Genoa (Italy); Zentilin, Patrizia, E-mail: Patrizia.Zentilin@unige.it [Gastroenterology Unit, Department of Internal Medicine, University of Genoa, 16132 Genoa (Italy); Marabotto, Elisa, E-mail: emarabotto@libero.it [Gastroenterology Unit, Department of Internal Medicine, University of Genoa, 16132 Genoa (Italy); Suh, Mina, E-mail: msuh@toxstrategies.com [ToxStrategies, Mission Viejo, CA 92692 (United States); Proctor, Deborah M., E-mail: dproctor@toxstrategies.com [ToxStrategies, Mission Viejo, CA 92692 (United States)

2016-09-01

Evaluation of the reducing capacity of human gastric fluid from healthy individuals, under fasted and fed conditions, is critical for assessing the cancer hazard posed by ingested hexavalent chromium [Cr(VI)] and for developing quantitative physiologically-based pharmacokinetic models used in risk assessment. In the present study, the patterns of Cr(VI) reduction were evaluated in 16 paired pre- and post-meal gastric fluid samples collected from 8 healthy volunteers. Human gastric fluid was effective both in reducing Cr(VI), as measured by using the s-diphenylcarbazide colorimetric method, and in attenuating mutagenicity in the Ames test. The mean (± SE) Cr(VI)-reducing ability of post-meal samples (20.4 ± 2.6 μg Cr(VI)/mL gastric fluid) was significantly higher than that of pre-meal samples (10.2 ± 2.3 μg Cr(VI)/mL gastric fluid). When using the mutagenicity assay, the decrease of mutagenicity produced by pre-meal and post-meal samples corresponded to reduction of 13.3 ± 1.9 and 25.6 ± 2.8 μg Cr(VI)/mL gastric fluid, respectively. These data are comparable to parallel results conducted by using speciated isotope dilution mass spectrometry. Cr(VI) reduction was rapid, with > 70% of total reduction occurring within 1 min and 98% of reduction is achieved within 30 min with post-meal gastric fluid at pH 2.0. pH dependence was observed with decreasing Cr(VI) reducing capacity at higher pH. Attenuation of the mutagenic response is consistent with the lack of DNA damage observed in the gastrointestinal tract of rodents following administration of ≤ 180 ppm Cr(VI) for up to 90 days in drinking water. Quantifying Cr(VI) reduction kinetics in the human gastrointestinal tract is necessary for assessing the potential hazards posed by Cr(VI) in drinking water. - Highlights: • Cr(VI) reduction capacity was greater in post-meal than paired pre-meal samples. • Cr(VI) reduction was rapid, pH dependent, and due to heat stable components. • Gastric fluid attenuates

Forkhead box protein A2, a pioneer factor for hepatogenesis, is involved in the expression of hepatic phenotype of alpha-fetoprotein-producing adenocarcinoma.

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Yamamura, Nobuhisa; Fugo, Kazunori; Kishimoto, Takashi

2017-09-01

Alpha-fetoprotein (AFP)-producing adenocarcinoma is a high-malignant variant of adenocarcinoma with a hepatic or fetal-intestinal phenotype. The number of cases of AFP-producing adenocarcinomas is increasing, but the molecular mechanism underlying the aberrant production of AFP is unclear. Here we sought to assess the role of Forkhead box A (FoxA)2, which is a pioneer transcription factor in the differentiation of hepatoblasts. FoxA2 expression was investigated in five cases of AFP-producing gastric adenocarcinomas by immunohistochemistry, and all cases showed FoxA2 expression. Chromatin immunoprecipitation revealed the DNA binding of FoxA2 on the regulatory element of AFP gene in AFP-producing adenocarcinoma cells. The inhibition of FoxA2 expression with siRNA reduced the mRNA expression of liver-specific proteins, including AFP, albumin, and transferrin. The inhibition of FoxA2 also reduced the expressions of liver-enriched nuclear factors, i.e., hepatocyte nuclear factor (HNF) 4α and HNF6, although the expressions of HNF1α and HNF1β were not affected. The same effect as FoxA2 knockdown in AFP producing adenocarcinoma cells was also observed in hepatocellular carcinoma cells. Our results suggest that FoxA2 plays a key role in the expression of hepatic phenotype of AFP-producing adenocarcinomas. Copyright © 2017 Elsevier GmbH. All rights reserved.

Adjuvant chemo-radiation for gastric adenocarcinoma: an institutional experience

International Nuclear Information System (INIS)

Aftimos, Philippe G; Nasr, Elie A; Nasr, Dolly I; Noun, Roger J; Nasr, Fady L; Ghosn, Marwan G; El Helou, Joelle A; Chahine, Georges Y

2010-01-01

Studies have shown that surgery alone is less than satisfactory in the management of early gastric cancer, with cure rates approaching 40%. The role of adjuvant therapy was indefinite until three large, randomized controlled trials showed the survival benefit of adjuvant therapy over surgery alone. Chemoradiation therapy has been criticized for its high toxicity. 24 patients diagnosed between September 2001 and July 2007 were treated with adjuvant chemoradiation. 18 patients had the classical MacDonald regimen of 4500 cGy of XRT and chemotherapy with 5-fluorouracil (5FU) and leucovorin, while chemotherapy consisted of 5FU/Cisplatin for 6 patients. This series consisted of non-metastatic patients, 17 females and 7 males with a median age of 62.5 years. 23 patients (96%) had a performance status of 0 or 1. The full course of radiation therapy (4500 cGy) was completed by 22 patients (91.7%). Only 7 patients (36.8%) completed the total planned courses of chemotherapy. 2 local relapses (10%), 2 regional relapses (10%) and 2 distant relapses (10%) were recorded. Time to progression has not been reached. 9 patients (37.5%) died during follow-up with a median overall survival of 75 months. Patients lost a mean of 4 Kgs during radiation therapy. We recorded 6 episodes of febrile neutropenia and the most frequent toxicity was gastro-intestinal in 17 patients (70.8%) with 9 (36%) patients suffering grade 3 or 4 toxicity and 5 patients (20%) suffering from grade 3 or 4 neutropenia. 4 (17%) patients required total parenteral nutrition for a mean duration of 20 days. 4 patients suffered septic shock (17%) and 1 patient developed a deep venous thrombosis and a pulmonary embolus. Adjuvant chemo-radiation for gastric cancer is a standard at our institution and has resulted in few relapses and an interesting median survival. Toxicity rates were serious and this remains a harsh regimen with only 36.8% of patients completing the full planned courses of chemotherapy. This is due to

Adjuvant chemo-radiation for gastric adenocarcinoma: an institutional experience

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Ghosn Marwan G

2010-06-01

Full Text Available Abstract Background Studies have shown that surgery alone is less than satisfactory in the management of early gastric cancer, with cure rates approaching 40%. The role of adjuvant therapy was indefinite until three large, randomized controlled trials showed the survival benefit of adjuvant therapy over surgery alone. Chemoradiation therapy has been criticized for its high toxicity. Methods 24 patients diagnosed between September 2001 and July 2007 were treated with adjuvant chemoradiation. 18 patients had the classical MacDonald regimen of 4500 cGy of XRT and chemotherapy with 5-fluorouracil (5FU and leucovorin, while chemotherapy consisted of 5FU/Cisplatin for 6 patients. Results This series consisted of non-metastatic patients, 17 females and 7 males with a median age of 62.5 years. 23 patients (96% had a performance status of 0 or 1. The full course of radiation therapy (4500 cGy was completed by 22 patients (91.7%. Only 7 patients (36.8% completed the total planned courses of chemotherapy. 2 local relapses (10%, 2 regional relapses (10% and 2 distant relapses (10% were recorded. Time to progression has not been reached. 9 patients (37.5% died during follow-up with a median overall survival of 75 months. Patients lost a mean of 4 Kgs during radiation therapy. We recorded 6 episodes of febrile neutropenia and the most frequent toxicity was gastro-intestinal in 17 patients (70.8% with 9 (36% patients suffering grade 3 or 4 toxicity and 5 patients (20% suffering from grade 3 or 4 neutropenia. 4 (17% patients required total parenteral nutrition for a mean duration of 20 days. 4 patients suffered septic shock (17% and 1 patient developed a deep venous thrombosis and a pulmonary embolus. Conclusions Adjuvant chemo-radiation for gastric cancer is a standard at our institution and has resulted in few relapses and an interesting median survival. Toxicity rates were serious and this remains a harsh regimen with only 36.8% of patients completing the

Computed Tomography (CT) Perfusion as an Early Predictive Marker for Treatment Response to Neoadjuvant Chemotherapy in Gastroesophageal Junction Cancer and Gastric Cancer - A Prospective Study

DEFF Research Database (Denmark)

Lundsgaard Hansen, Martin; Fallentin, Eva; Lauridsen, Carsten

2014-01-01

OBJECTIVES: To evaluate whether early reductions in CT perfusion parameters predict response to pre-operative chemotherapy prior to surgery for gastroesophageal junction (GEJ) and gastric cancer. MATERIALS AND METHODS: Twenty-eight patients with adenocarcinoma of the gastro-esophageal junction (GEJ......-operative chemotherapy in GEJ and gastric cancer. As a single diagnostic test, CT Perfusion only has moderate sensitivity and specificity in response assessment of pre-operative chemotherapy making it insufficient for clinical decision purposes....

Increasing trend of metronidazole resistance in the treatment of ...

African Journals Online (AJOL)

Helicobacter pylori are gram negative spiral bacteria that colonize the human stomach. Infection with H. pylori is associated with chronic gastritis, peptic ulcer, gastric adenocarcinoma and gastric mucosaassociated lymphoid tissue (MALT) lymphoma. Antibiotic resistance is an ever increasing problem with the treatment of ...

Intracranial Metastasis in a Patient with Hepatocellular Carcinoma and Gastric Cancer

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Akinobu Tawada

2014-03-01

Full Text Available A 76-year-old man was referred to our hospital with visual disturbance, weakness of the left upper and lower limbs, and gait disturbance. He had previously received transarterial chemoembolization for hepatocellular carcinoma (HCC 3 and 10 years ago. When he had received radiofrequency ablation for HCC recurrence 2 years ago, total gastrectomy was also performed for his gastric cancer. Subsequently, sorafenib had been administrated for concomitant lung metastatic tumors. On admission, MRI revealed an intra-axial tumor with perifocal edema. The level of carcinoembryonic antigen, but not alpha-fetoprotein, markedly increased. The tumor was successfully removed by craniotomy and pathological examination revealed that it was composed of adenocarcinoma, which was consistent with the primary gastric cancer. After surgery, his neurological disturbances rapidly resolved. Additional gamma-knife treatment was also performed for another small brain metastasis detected after craniotomy. Subsequently, sorafenib administration was discontinued and S-1 was administered postoperatively. Successful treatment of intracranial metastasis of gastric cancer is important and meaningful, even in patients with multiple primary malignancies.

Mouse Models of Gastric Cancer

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Hayakawa, Yoku; Fox, James G.; Gonda, Tamas; Worthley, Daniel L.; Muthupalani, Sureshkumar; Wang, Timothy C.

2013-01-01

Animal models have greatly enriched our understanding of the molecular mechanisms of numerous types of cancers. Gastric cancer is one of the most common cancers worldwide, with a poor prognosis and high incidence of drug-resistance. However, most inbred strains of mice have proven resistant to gastric carcinogenesis. To establish useful models which mimic human gastric cancer phenotypes, investigators have utilized animals infected with Helicobacter species and treated with carcinogens. In addition, by exploiting genetic engineering, a variety of transgenic and knockout mouse models of gastric cancer have emerged, such as INS-GAS mice and TFF1 knockout mice. Investigators have used the combination of carcinogens and gene alteration to accelerate gastric cancer development, but rarely do mouse models show an aggressive and metastatic gastric cancer phenotype that could be relevant to preclinical studies, which may require more specific targeting of gastric progenitor cells. Here, we review current gastric carcinogenesis mouse models and provide our future perspectives on this field. PMID:24216700

Serum HER 2 extracellular domain level is correlated with tissue HER 2 status in metastatic gastric or gastro-oesophageal junction adenocarcinoma.

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Shu-Qin Dai

Full Text Available BACKGROUND: To explore the association between serum human epidermal growth factor receptor 2 (HER 2 extracellular domain (ECD levels and tissue HER 2 status in metastatic gastric cancer. PATIENTS AND METHODS: HER 2 status was retrospectively analyzed in 219 advanced gastric or gastroesophageal junction (GEJ patients. Serum HER 2 ECD was measured by chemiluminescent assay and tissue HER 2 was assessed by fluorescent in situ hybridisation (FISH and immunohistochemistry (IHC assay. RESULTS: Significant associations were found between serum HER 2 ECD levels and tissue HER 2 status. Twenty-four patients had HER 2 ECD levels >16.35 ng/mL, which has a sensitivity of 51.4% and a specificity of 97.3% to predict tissue HER 2 status. When the cut-off value was increased to 22 ng/mL, then all 12 patients with serum HER 2 ECD levels>22 ng/mL were tissue HER 2 positive, corresponding to a specificity of 100% and a sensitivity of 32.4%. High serum HER 2 ECD levels were strongly associated with the intestinal histological type (Lauren's classification, liver metastasis, multiple metastasis (>2 and increased LDH levels, but not with overall survival. CONCLUSIONS: The high specificity of the serum HER 2 ECD assay in predicting tissue HER 2 status suggests its potential as a surrogate marker of the HER 2 status in gastric cancer.

Common activation of canonical Wnt signaling in pancreatic adenocarcinoma.

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Marina Pasca di Magliano

2007-11-01

Full Text Available Pancreatic ductal adenocarcinoma (PDA is an extremely aggressive malignancy, which carries a dismal prognosis. Activating mutations of the Kras gene are common to the vast majority of human PDA. In addition, recent studies have demonstrated that embryonic signaling pathway such as Hedgehog and Notch are inappropriately upregulated in this disease. The role of another embryonic signaling pathway, namely the canonical Wnt cascade, is still controversial. Here, we use gene array analysis as a platform to demonstrate general activation of the canonical arm of the Wnt pathway in human PDA. Furthermore, we provide evidence for Wnt activation in mouse models of pancreatic cancer. Our results also indicate that Wnt signaling might be activated downstream of Hedgehog signaling, which is an early event in PDA evolution. Wnt inhibition blocked proliferation and induced apoptosis of cultured adenocarcinoma cells, thereby providing evidence to support the development of novel therapeutical strategies for Wnt inhibition in pancreatic adenocarcinoma.

Down-regulation of telomerase activity in DLD-1 human colorectal adenocarcinoma cells by tocotrienol

International Nuclear Information System (INIS)

Eitsuka, Takahiro; Nakagawa, Kiyotaka; Miyazawa, Teruo

2006-01-01

As high telomerase activity is detected in most cancer cells, inhibition of telomerase by drug or dietary food components is a new strategy for cancer prevention. Here, we investigated the inhibitory effect of vitamin E, with particular emphasis on tocotrienol (unsaturated vitamin E), on human telomerase in cell-culture study. As results, tocotrienol inhibited telomerase activity of DLD-1 human colorectal adenocarcinoma cells in time- and dose-dependent manner, interestingly, with δ-tocotrienol exhibiting the highest inhibitory activity. Tocotrienol inhibited protein kinase C activity, resulting in down-regulation of c-myc and human telomerase reverse transcriptase (hTERT) expression, thereby reducing telomerase activity. In contrast to tocotrienol, tocopherol showed very weak telomerase inhibition. These results provide novel evidence for First time indicating that tocotrienol acts as a potent candidate regulator of telomerase and supporting the anti-proliferative function of tocotrienol

Plasma sample based analysis of gastric cancer progression using targeted metabolomics.

Science.gov (United States)

Lario, Sergio; Ramírez-Lázaro, Maria José; Sanjuan-Herráez, Daniel; Brunet-Vega, Anna; Pericay, Carles; Gombau, Lourdes; Junquera, Félix; Quintás, Guillermo; Calvet, Xavier

2017-12-19

Gastric carcinogenesis is a multifactorial process described as a stepwise progression from non-active gastritis (NAG), chronic active gastritis (CAG), precursor lesions of gastric cancer (PLGC) and gastric adenocarcinoma. Gastric cancer (GC) 5-year survival rate is highly dependent upon stage of disease at diagnosis, which is based on endoscopy, biopsy and pathological examinations. Non-invasive GC biomarkers would facilitate its diagnosis at early stages leading to improved GC prognosis. We analyzed plasma samples collected from 80 patients diagnosed with NAG without H. pylori infection (NAG-), CAG with H. pylori infection (CAG+), PLGC and GC. A panel of 208 metabolites including acylcarnitines, amino acids and biogenic amines, sphingolipids, glycerophospholipids, hexoses, and tryptophan and phenylalanine metabolites were quantified using two complementary quantitative approaches: Biocrates AbsoluteIDQ®p180 kit and a LC-MS method designed for the analysis of 29 tryptophan pathway and phenylalanine metabolites. Significantly altered metabolic profiles were found in GC patients that allowing discrimination from NAG-, CAG+ and PLGC patients. Pathway analysis showed significantly altered tryptophan and nitrogen metabolic pathways (FDR P < 0.01). Three metabolites (histidine, tryprophan and phenylacetylglutamine) discriminated between non-GC and GC groups. These metabolic signatures open new possibilities to improve surveillance of PLGC patients using a minimally invasive blood analysis.

Urothelial-Type adenocarcinoma of the prostate mimicking metastatic colorectal adenocarcinoma

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Brian P. Adley

2006-12-01

Full Text Available Adenocarcinoma arising in urinary bladder or prostatic urethra is uncommon. When they occur, the tumor can be mistaken for metastatic lesions, especially from the colon. Here we report the fifth case of a primary urothelial-type adenocarcinoma arising in the prostate which showed enteric differentiation. The patient was a 55 year-old male whose prostatic needle core biopsy showed a high grade adenocarcinoma which was initially thought to be metastatic colon cancer. A follow-up colonoscopy was unremarkable. Subsequent prostatectomy revealed a high grade adenocarcinoma which was positive for cytokeratins 7 and 20, carcinoembryonic antigen, CDX2, and high molecular weight cytokeratin, and negative for prostate specific antigen, prostate specific acid phosphatase and AMACR. A diagnosis of urothelial-type adenocarcinoma of the prostate was rendered. We review the literature regarding this entity, and discuss the differential diagnosis, emphasizing utility of immunohistochemistry in making the diagnosis. Finally, we speculate on the behavior of these rare tumors.

Ghrelin stimulates gastric emptying and hunger in normal-weight humans

DEFF Research Database (Denmark)

Levin, F; Edholm, T; Schmidt, P T

2006-01-01

CONTEXT: Ghrelin is produced primarily by enteroendocrine cells in the gastric mucosa and increases gastric emptying in patients with gastroparesis. MAIN OBJECTIVE: The objective of the study was to evaluate the effect of ghrelin on gastric emptying, appetite, and postprandial hormone secretion i...

Recurrent amplification of RTEL1 and ABCA13 and its synergistic effect associated with clinicopathological data of gastric adenocarcinoma.

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Araújo, T M; Seabra, A D; Lima, E M; Assumpção, P P; Montenegro, R C; Demachki, S; Burbano, R M; Khayat, A S

2016-01-01

Despite progression in treatment of gastric cancer, prognosis of patients remains poor, in part due to the low rate of diagnosis during its early stages. This paradigm implies the necessity to identify molecular biomarkers for early gastric cancer diagnosis, as well as for disease monitoring, thus contributing to the development of new therapeutic approaches. In a previous study, performed by array-Comparative Genomic Hybridization, we described for the first time in literature recurrent amplification of RTEL1 and ABCA13 genes in gastric cancer. Thus, the aim of the present study was to validate recurrent amplification of RTEL1 and ABCA13 genes and associate CNV status with clinicopathological data. Results showed RTEL1 and ABCA13 amplification in 38 % of samples. Statistical analysis demonstrated that RTEL amplification is more common in older patients and more associated with intestinal type and ABCA13 amplification increases the risk of lymph node metastasis and is more common in men. Co-amplification of these genes showed a significant association with advanced staging. aCGH is a very useful tool for investigating novel genes associated with carcinogenesis and RTEL1 amplification may be important for the development of gastric cancer in older patients, besides being a probable event contributing for chromosomal instability in intestinal gastric carcinogenesis. ABCA13 amplification may have age-specific function and could be considered a useful marker for predicting lymph node metastasis in resected gastric cancer patients in early stage. Lastly, RTEL1 and ABCA13 synergistic effect may be considered as a putative marker for advanced staging in gastric cancer patients.

Metástase de câncer gástrico simulando neoplasia primária de pulmão: relato de caso e revisão da literatura Gastric cancer metastasis mimicking primary lung cancer: case report and review of the literature

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Dante Luiz Escuissato

2002-03-01

Full Text Available O adenocarcinoma gástrico apresenta, freqüentemente, disseminação por extensão direta para órgãos vizinhos. Metástases para sítios distantes, como o pulmão, são menos freqüentes, sugerindo usualmente outras doenças. O objetivo deste artigo é apresentar o caso de um paciente de 47 anos de idade, cujos exames de imagem (radiografias simples e tomografia computadorizada de tórax apresentaram características sugestivas de neoplasia pulmonar primária e com diagnóstico simultâneo de câncer gástrico evidenciado pela endoscopia digestiva alta. A biópsia, guiada por fibrobroncoscopia, da massa torácica confirmou o diagnóstico de metástase pulmonar de adenocarcinoma gástrico. Além da apresentação do caso, é feita uma revisão do padrão de disseminação do câncer gástrico.Gastric cancer frequently presents intraperitoneal spread. Distant metastases are rare. The authors describe a case of a 47-year-old white man, long-term cigarette smoker, who had a right upper lobe mass seen on plain films and computed tomography of the chest. A gastric adenocarcinoma was concomitantly diagnosed by endoscopic examination. A bronchoscopy guided biopsy showed that the lung mass was in fact a metastasis from gastric adenocarcinoma. In this article, the imaging findings of gastric cancer and the patterns of dissemination to other organs are reviewed.

Helicobacter pylori and gastric cancer: correlation with gastritis, intestinal metaplasia, and tumour histology.

OpenAIRE

Wee, A; Kang, J Y; Teh, M

1992-01-01

This study aimed to examine the association between Helicobacter pylori, histological gastritis, and intestinal metaplasia in gastric cancers of different histological types. A total of 169 gastrectomy specimens received in one pathology department were studied. Altogether 156 were adenocarcinomas (intestinal type 87, diffuse type 50, mixed type 19). Gastritis occurred in 137 of 163 body specimens (84%) and in 126 of 131 antral specimens (96%). Its presence was unrelated to tumour histology. ...

Assessment of lymphovascular invasion in gastric carcinoma; do they always indicate lymph node metastasis?

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Kricha Pande

2018-04-01

Full Text Available Background: Stomach cancer is one of the leading causes of cancer death. The grading and staging of this cancer plays an important prognostic role. Lymphovascular invasion predicts poor outcome in gastric cancer. Among the others, lymphovascular invasion provides useful information for the clinical management of patients with gastric cancer. Nevertheless, data about lymphovascular invasion in early-stage and in lymph node-positive gastric cancer are lacking. Hence, significance of lymphovascular invasion to metastatic lymph nodes impacting nodal status in gastric cancer has been studied in this study.Materials and methods: This is a retrospective analysis of twenty nine (29 histologically confirmed gastric carcinoma cases received in the department of Pathology at NMCTH dating from October 2014 to September 2016.Results:  There was male preponderance to gastric carcinoma with male to female ratio of 2.2:1. The age varied from 31- 84 years. There were 17 cases (59% of intestinal type and 11 cases (38% of diffuse type of gastric carcinoma and 1 case (3% of adeno-neuroendocrine carcinoma. Microscopic evaluation for depth of invasion showed tumor invasion till the subserosal connective tissue layer (69% suggesting pT3 stage.  lymphovascular invasion was identified in 21 cases (72%. There was statistically significant correlation (p value 0.01 between   lymphovascular invasion and nodal status (N0 status. Conclusion: Presence of lymphovascular invasion is considered as poor prognostic marker in case of gastric adenocarcinoma. Pathologist have been reporting their presence or absence in each gastrectomy reports related to gastric carcinoma.This study has established a significant relation between presence of lymphovascular invasion and nodal staging of gastric carcinoma.

N-methyl-N-nitro-N-nitrosoguanidine-mediated ING4 downregulation contributed to the angiogenesis of transformed human gastric epithelial cells.

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