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Gastric Carcinoma (gastric + carcinoma)
Terms modified by Gastric Carcinoma Selected AbstractsPrognostic Significance of Matrix Metalloproteinase-7 (MMP-7) Expression at the Invasive Front in Gastric CarcinomaCANCER SCIENCE, Issue 3 2002Xiu Ping Liu To evaluate the clinicopathological significance of matrix metalloproteinase-7 (MMP-7) expression in gastric carcinoma, we investigated immunohistochemically MMP-7 expression in 214 gastric carcinomas, and examined its relations with the clinicopathologic parameters including patient prognosis. MMP-7 expressed predominantly in cancer cells, and MMP-7-positive tumor cells were preferentially found in deeply invading nests, especially at the invasive front. The mean MMP-7 labeling index (LI) at the invasive front was significantly higher in tumors invading or penetrating the muscularis propria and in stages II-IV than within the submucosal layer and in stage I, respectively (P<0.001). Statistical analysis revealed that MMP-7 LI at the invasive front was related to lymph node metastasis, vascular invasion, and lymphatic permeation, when all 214 cases were examined as one group (P<0.05 for all), and the cases with high MMP-7 expression at the invasive front showed significantly more unfavorable prognosis as compared with that of low MMP-7 expression tumors (P<0.01). Multivariate analysis revealed that TNM stage and MMP-7 expression status at the invasive front were independent prognostic factors (P=0.0017, relative risk (RR)=3.12; P=0.0019, RR=2.67, respectively). Our findings indicated that expression of MMP-7 at the invasive front is closely associated with local invasiveness, and might be a reliable prognostic marker for patients with gastric carcinoma. [source] Abnormal Expression of p16INK4a, Cyclin D1, Cyclin-Dependent Kinase 4 and Retinoblastoma Protein in Gastric Carcinomas,JOURNAL OF SURGICAL ONCOLOGY, Issue 1 2008Ichiro Kishimoto MD Abstract Background and Objectives The p16INK4a (p16), cyclin D1, cyclin-dependent kinase (CDK) 4 and retinoblastoma (Rb) genes are components of the Rb pathway that controls the G1-S checkpoint of the cell cycle. The aim of this study was to assess the relationship between their abnormalities and clinicopathological features in gastric carcinomas. Mehtods Immunohistochemical analysis of the encoded proteins was performed on a series of 158 cases. Results Loss of p16/Rb protein (pRb) expression and overexpression of cyclin D1/CDK4 were observed in 49%/40% and 37%/37% of gastric carcinomas, respectively. At least 1 of these abnormalities was found in 86% of the cases and a positive correlation was noted between p16 and pRb (P,=,0.009). Cyclin D1 (P,=,0.042) and CDK4 (P,=,0.008) overexpession was inversely associated with lymph node metastasis and depth of invasion, respectively. Loss of pRb expression was more frequently in diffuse type lesions than in the intestinal type (P,=,0.022). The patients with p16+/pRb,/cyclin D1,/CDK4, or p16,/pRb+/cyclin D1,/CDK4, tumors demonstrated particularly poor survival. With multivariate survival analysis, only depth of invasion and TNM stage could be proven as independent predictors. Conclusions The Rb pathway is disrupted in the vast majority of gastric carcinomas. This study also identified specific immunohistochemical marker profiles for prognosis. J. Surg. Oncol. 2008;98:60,66. © 2008 Wiley-Liss, Inc. [source] Prognostic indicators of gastric carcinoma confined to the muscularis propriaHISTOPATHOLOGY, Issue 1 2007H Son Aims:, Gastric carcinoma confined to the muscularis propria (MPGC) is considered an intermediate-stage carcinoma. A method of discriminating between more favourable and less favourable prognostic groups of this entity is critically needed in dealing with this heterogeneous disease. The aim of this study was to examine the correlation between survival of patients with MPGC and its various clinicopathological parameters. Methods and results:, Various clinicopathological parameters were studied in 171 tissue samples including: macroscopic appearance, size, age, sex, stage, invasion depth, Lauren and Ming classifications, extent, lymphatic emboli and nodal metastasis. Tumours macroscopically resembling early gastric cancers, younger patient age, absence of lymphatic tumour emboli and lower stage were significantly associated with better prognosis of MPGC by univariate analysis. Tumours macroscopically resembling early gastric cancers, younger patient age and Lauren's diffuse type were significantly associated with a better prognosis of MPGC by multivariate analysis. Conclusions:, These indicators are practical parameters for predicting patient prognosis in clinical practice. The description of these parameters should be carefully noted in the final report and pathologists should evaluate the macroscopic appearance of MPGC. [source] Helicobacter pylori activates protein kinase C delta to control Raf in MAP kinase signalling: Role in AGS epithelial cell scattering and elongationCYTOSKELETON, Issue 10 2009Sabine Brandt Abstract Helicobacter pylori is a major etiological agent in the development of chronic gastritis, duodenal ulcer and gastric carcinoma in humans. Virulent H. pylori strains harbor a type IV secretion system (T4SS) encoded by the cag pathogenicity island. This T4SS injects the CagA protein into gastric epithelial cells leading to actin-cytoskeletal rearrangements followed by cell elongation and scattering. Here we report that PMA (4,-phorbol-12-myristate-13-acetate), a well-known cell-permeable activator of protein kinase C (PKC), induces a remarkably similar cellular phenotype as compared to infection with H. pylori. PKCs comprise a large family of serine/threonine kinases which are important for multiple physiological processes of host cells. We therefore investigated the role of individual PKC members and the signalling pathways involved in phenotypical outcome. Using isoform-specific silencing RNAs and pharmacological inhibitors we found that two isoforms, PKC-, and PKC-,, were essential for both PMA- and H. pylori -induced elongation phenotype. Furthermore, we provide evidence that PKC-, activity is profoundly stimulated during the course of infection using activation-specific antibodies against PKC phosphorylated at threonine residue 505 or serine residue 660. Infection with H. pylori wild-type and mutants showed that at least two bacterial factors activate PKC-, in a time-dependent manner, one of which is CagA. Immunofluorescence microscopy studies further demonstrated that phosphorylated PKC-, is accumulated and recruited to dynamic actin-structures at the cell membrane. Finally, we show that PKC-, specifically targets Raf kinase to stimulate the Erk1/2 kinase pathway, which is also crucial for phenotypical outcome. Thus, PKC-, is another important mediator of H. pylori -induced pathogenesis. Cell Motil. Cytoskeleton 2009. © 2009 Wiley-Liss, Inc. [source] MAGNIFICATION ENDOSCOPIC VIEW OF AN EARLY GASTRIC CANCER USING ACETIC ACID AND NARROW-BAND IMAGING SYSTEMDIGESTIVE ENDOSCOPY, Issue 2006Hideki Toyoda A 62-year-old woman was referred to Mie University Hospital, Tsu, Japan, for examination of upper gastrointestinal tract. The conventional endoscopy showed a slightly depressed lesion on the greater curvature at the gastric body. The surface of surrounding non-neoplastic mucosa using magnification endoscopy with acetic acid was gyrus-villous pattern whereas the surface of the lesion was rough. Furthermore, magnification endoscopy using acetic acid and narrow-band imaging system visualized clearer fine surface pattern of carcinoma. The lesion had a rough mucosa with irregularly arranged small pits. The lesion was resected completely by endoscopic mucosal resection with insulated-tip electrosurgical knife. Narrow-band imaging system with acetic acid may be able to visualize not only the capillary pattern but also the fine surface pattern of gastric carcinoma. [source] Three-dimensional endoscopic ultrasonography for the assessment of early gastric carcinoma invasion: could it provide diagnostic innovations?DIGESTIVE ENDOSCOPY, Issue 2 2002EMAN A. SABET Background: This study aimed to evaluate a three-dimensional endoscopic ultrasonographic (3-D EUS) system in the assessment of the tumor invasion depth of early gastric carcinoma. Methods: Sixty-nine macroscopically early cancer lesions in 67 patients were recruited in an in vivo study. The surgically resected gastric specimens of 30 of them were re-examined in an ex vivo study. An Olympus 3-D EUS imaging system was employed in both studies. Diagnostic accuracy for tumor invasion depth was evaluated and compared with histopathological sections stained by H&E and Masson's trichrome stain. Reconstructed surface-rendering images were evaluated and compared with the endoscopic and macroscopic findings. Results: Three-dimensional EUS allowed rapid tomographic assessment of the lesions in both the in vivo and ex vivo studies. The accuracy of 3-D EUS for the assessment of tumor invasion depth was 87% in the in vivo study. The accuracy rate was significantly lower (P = 0.03) for the cancer lesions associated with ulcer fibrosis (74%) than for those with no fibrosis (97%). In the 30 subjects who underwent both studies, the accuracy rates were higher in the ex vivo than the in vivo study (94%vs 77% for all the lesions, and 93%vs 74% for cancers associated with fibrosis), but were not statistically significant. The rates of good surface-rendering images were 64% and 94% in the in vivo and ex vivo studies, respectively. The differences were attributed to the clearer dual-plane reconstruction images obtained in the ex vivo study in absence of motion artifacts. Conclusions: Three-dimensional EUS is a promising imaging technique for the assessment of tumor invasion depth of early gastric cancer. [source] A case of small-cell gastric carcinoma with an adenocarcinoma component and hepatic metastases: treatment with systemic and intra-hepatic chemotherapyEUROPEAN JOURNAL OF CANCER CARE, Issue 5 2007T. CIOPPA md Primary small-cell carcinoma (SmCC) of the stomach is a rare neoplasm with a poor prognosis and unclear histogenesis: to date, only 50 cases, including ours, have been reported in the literature. In the World Health Organization gastrointestinal tumours' classification, SmCC of the stomach has been recognized as an ,independent entity affecting the stomach'. In this paper, the authors present a clinical case and the surgical treatment of an adult with a SmCC of the stomach associated with gastric adenocarcinoma. After laparotomy, a large neoplasm with locoregional extension and multiple liver metastases were found. A palliative resection, subtotal gastrectomy, was performed, followed by systemic and intra-hepatic chemotherapy: computed tomography scan demonstrated a marked response, but the patient died 15 months after the operation. A review of the literature showed that the diagnosis of gastric SmCC is based on immunohistochemical findings. Our experience confirmed the high aggressiveness of this neoplasm, which is generally diagnosed in advanced stage and is unresponsive to chemotherapy, but the combined use of systemic and intra-hepatic chemotherapy shows an acceptable result in a palliative care perspective. [source] Identification of membrane-bound serine proteinase matriptase as processing enzyme of insulin-like growth factor binding protein-related protein-1 (IGFBP-rP1/angiomodulin/mac25)FEBS JOURNAL, Issue 3 2006Sanjida Ahmed Insulin-like growth factor (IGF) binding protein-related protein-1 (IGFBP-rP1) modulates cellular adhesion and growth in an IGF/insulin-dependent or independent manner. It also shows tumor-suppressive activity in vivo. We recently found that a single-chain IGFB-rP1 is proteolytically cleaved to a two-chain form by a trypsin-like, endogenous serine proteinase, changing its biological activities. In this study, we attempted to identify the IGFBP-rP1-processing enzyme. Of nine human cell lines tested, seven cell lines secreted IGFBP-rP1 at high levels, and two of them, ovarian clear cell adenocarcinoma (OVISE) and gastric carcinoma (MKN-45), highly produced the cleaved IGFBP-rP1. Serine proteinase inhibitors effectively blocked the IGFBP-rP1 cleavage in the OVISE cell culture. The conditioned medium of OVISE cells did not cleave purified IGFBP-rP1, but their membrane fraction had an IGFBP-rP1-cleaving activity. The membrane fraction contained an 80-kDa gelatinolytic enzyme, which was identified as the membrane-type serine proteinase matriptase (MT-SP1) by immunoblotting. When the membrane fraction was separated by SDS/PAGE, the IGFBP-rP1-cleaving activity comigrated with matriptase. A soluble form of matriptase purified in an inhibitor-free form efficiently cleaved IGFBP-rP1 at the same site as that found in a naturally cleaved IGFBP-rP1. Furthermore, small interfering RNAs for matriptase efficiently blocked both the matriptase expression and the cleavage of IGBP-rP1 in OVISE cells. These results demonstrate that IGFBP-rP1 is processed to the two-chain form by matriptase on the cell surface. [source] Effects of Aspirin on the Development of Helicobacter pylori -Induced Gastric Inflammation and Heterotopic Proliferative Glands in Mongolian GerbilsHELICOBACTER, Issue 1 2008Guo Qing Li Abstract Background: Helicobacter pylori infection is a major cause of gastritis and gastric carcinoma. Aspirin has anti-inflammatory and antineoplastic activity. The aim of the present study was to determine the effects of aspirin on H. pylori -induced gastritis and the development of heterotopic proliferative glands. Methods: H. pylori strain SS1 was inoculated into the stomachs of Mongolian gerbils. Two weeks after inoculation, the animals were fed with the powder diets containing 0 p.p.m. (n = 10), 150 p.p.m. (n = 10), or 500 p.p.m. (n = 10) aspirin. Mongolian gerbils were killed after 36 weeks of infection. Uninfected Mongolian gerbils (n = 10) were used as controls. Histologic changes, epithelial cell proliferation and apoptosis, and prostaglandin E2 (PGE2) levels of gastric tissue were determined. Results: H. pylori infection induced gastric inflammation. Administration of aspirin did not change H. pylori -induced gastritis, but alleviated H. pylori -induced hyperplasia and the development of heterotopic proliferative glands. Administration of aspirin accelerated H. pylori -associated apoptosis but decreased H. pylori -associated cell proliferation. In addition, the increased gastric PGE2 levels due to H. pylori infection were suppressed by treatment with aspirin, especially at the dose of 500 p.p.m. Conclusions: Aspirin alleviates H. pylori -induced hyperplasia and the development of heterotopic proliferative glands. Moreover, aspirin increases H. pylori -induced apoptosis. We demonstrated the antineoplastic activities of aspirin in H. pylori -related gastric carcinogenesis. [source] Seroprevalence of Helicobacter pylori Infection Among Schoolchildren and Teachers in TaiwanHELICOBACTER, Issue 3 2007Ding-Bang Lin Abstract Background:,Helicobacter pylori are associated with chronic antral gastritis that is related to duodenal ulcer, gastric ulcer, and probably gastric adenocarcinoma. Infection of H. pylori during childhood is considered an important risk factor for gastric carcinoma in adult life. Materials and Methods:, To examine the epidemiologic characteristics of H. pylori infection among schoolchildren in central Taiwan, a community-based survey was carried out using stratified sampling in 10 elementary schools and three junior high schools including students and theirs teachers. Serum specimens of 1950 healthy schoolchildren (aged 9,15 years old) and 253 teachers who were randomly sampled were screened for the H. pylori antibodies by enzyme-linked immunosorbent assay. Statistical analysis was performed by using the spss for Windows statistical software system. Results:, A total of 332 subjects were H. pylori antibodies positive, giving an overall prevalence of 15.1%. The age-specific seropositive rates were 11.0% in 9,12 years age group, 12.3% in 13,15 years age group, and 45.1% in the teacher group. The older the age, the higher the seroprevalence (OR = 11.53; 95% CI = 6.73,19.74; p < .001 for children vs. teachers). There was no difference in the seroprevalence of H. pylori infection by gender, ethnicity, geographical area, socioeconomic level, parental education, sibship size, family members, and source of drinking water. Conclusion:, The teachers had a much higher prevalence of H. pylori antibodies. The finding suggests that these teachers (adults) might be infected in their early childhood and implies that the poor environmental and hygienic conditions might be responsible for it. It seemed that poor water supply system, sewage disposal, and other environmental hygiene in adult might play some roles in H. pylori infection in Taiwan (before early 1980s). [source] Pathogenesis of Helicobacter pylori InfectionHELICOBACTER, Issue 2006Masanori Hatakeyama Abstract Much interest has been shown in the relationship between Helicobacter pylori infection and gastric carcinogenesis. It is becoming clearer that H. pylori strains carrying a functional cag pathogenicity island (cagPAI), which encodes the type IV secretion system (TFSS) and its effector CagA, play an important role in the development of gastric carcinoma. Furthermore, genetic polymorphism present in the cagA gene appears to influence the degree of an individual cagPAI-positive H. pylori to elicit gastric mucosal lesions, and this process is significantly affected by host genetic polymorphisms such as proinflammatory cytokine gene polymorphisms. Pathomechanism of gastric carcinogenesis associated with H. pylori includes bacteria,host interaction leading to morphologic alterations such as atrophic gastritis and gastrointestinal metaplasia mediated by COX-2 overexpression, cancer cell invasion, and neo-angiogenesis via TLR2/TLR9 system and transcription factors (e.g., NF-,B) activation. In addition, H. pylori infection triggers adhesion molecule expression and activity and produces an enhancement in oxidative stress interacting with gastric production of appetite hormone ghrelin and nonsteroidal anti-inflammatory drugs. [source] Tooth Loss and Helicobacter pylori Seropositivity: the Newcastle Thousand Families Cohort Study at Age 49,51 YearsHELICOBACTER, Issue 1 2005Mark S. Pearce ABSTRACT Background.,Helicobacter pylori, one of the commonest chronic bacterial infections of humankind, is an important risk factor for gastric carcinoma. It has also been suggested to be present in dental plaque. This study investigated the potential link between the number of teeth lost and H. pylori seropositivity at age 50 years. Methods.,H. pylori seropositivity at age 50 years was investigated among 334 individuals born in Newcastle upon Tyne, United Kingdom, in May and June 1947 and related to the number of teeth lost, after adjusting for socioeconomic status. Results., The unadjusted risk of being seropositive for H. pylori increased with increasing number of teeth lost (odds ratio per tooth 1.03, 95% confidence interval 1.01,1.06, p = .019). However, after adjustment for socioeconomic status at birth and at age 50 years, the relationship was no longer significant (p = .36). Conclusions., Our results, obtained using prospectively collected data, suggest that any relationship between poor oral health and seropositivity to H. pylori may be due to both tooth loss and H. pylori colonization being associated with socioeconomic status and related factors. [source] The Relationship Between Helicobacter pylori Infection, the Virulence Genotypes of the Infecting Strain and Gastric Cancer in the African SettingHELICOBACTER, Issue 4 2001J. A. Louw Abstract Background. The relationship between Helicobacter pylori infection and gastric carcinoma remains controversial, especially in the African setting where infection is common, while gastric cancer is perceived to be uncommon, the basis of the so called ,African enigma'. This discrepancy between infection and the development of disease is commonly attributed to differences in host, environment and bacterial factors. Interest in the bacterial factors has focused on heterogeneity in the so-called ,virulence genes'. Aim. The aim of this prospective, case-controlled study was to establish whether H. pylori infection is significantly associated with gastric cancer and to investigate whether gastric cancer is associated with genotypically distinct (as it relates to the candidate virulence genes) organisms in this population. Methods. Patients with histologically confirmed gastric cancer were matched with nonulcer dyspeptic controls for age (within 5 years), gender and ethnicity. Helicobacter pylori status was determined by RUT, histology, culture and serology (locally validated and used as default determinant of H. pylori status). Tumors were classified according to the Lauren classification. The ,virulence genotype' of 17 paired culture samples was determined by previously described and validated molecular techniques (cagA presence, vacA alleles, structure of the cag pathogenicity island and analysis of the iceA alleles). Categorical variables were analysed by the ,2 test. Results. Forty-eight patients (median age 59 years) could be adequately matched to controls. 39/48 (81%) cases and 43/48 (90%) controls were H. pylori positive (NS). Significant differences in the virulence genotypes of infecting strains were noted: vacAs2-controls 24%, cases 0%, p < .00001; vacAs1 present , cases 100%, controls 76%, p < .05; cagA -3,-length > 650 bp , cases 47%, controls 0%, p < .002; cag pathogenicity island intact , cases 82%, controls 43%, p < .04; iceA1 , cases 53%, controls 6%, p < .005. cagA was found in all subjects. Conclusion. This study indicates that, in this African population at least, there is no difference in the prevalence of H. pylori infection when comparing gastric cancer cases with matched controls. However, the findings suggest that gastric cancer may be associated with infection by organisms that are genotypically different from those not associated with disease. [source] Prognostic indicators of gastric carcinoma confined to the muscularis propriaHISTOPATHOLOGY, Issue 1 2007H Son Aims:, Gastric carcinoma confined to the muscularis propria (MPGC) is considered an intermediate-stage carcinoma. A method of discriminating between more favourable and less favourable prognostic groups of this entity is critically needed in dealing with this heterogeneous disease. The aim of this study was to examine the correlation between survival of patients with MPGC and its various clinicopathological parameters. Methods and results:, Various clinicopathological parameters were studied in 171 tissue samples including: macroscopic appearance, size, age, sex, stage, invasion depth, Lauren and Ming classifications, extent, lymphatic emboli and nodal metastasis. Tumours macroscopically resembling early gastric cancers, younger patient age, absence of lymphatic tumour emboli and lower stage were significantly associated with better prognosis of MPGC by univariate analysis. Tumours macroscopically resembling early gastric cancers, younger patient age and Lauren's diffuse type were significantly associated with a better prognosis of MPGC by multivariate analysis. Conclusions:, These indicators are practical parameters for predicting patient prognosis in clinical practice. The description of these parameters should be carefully noted in the final report and pathologists should evaluate the macroscopic appearance of MPGC. [source] The utility of cytokeratin subsets in distinguishing Barrett's-related oesophageal adenocarcinoma from gastric adenocarcinomaHISTOPATHOLOGY, Issue 4 2001A H Ormsby Aims: Accurate tumour classification is critical for meaningful epidemiological studies in the assessment of cancer incidence rates and trends. Differentiating primary gastric carcinoma from oesophageal carcinoma can be difficult, especially when tumours are large and involve both the oesophagus and stomach. Furthermore, adenocarcinomas of both organs typically are of intestinal histological type and arise in a background of intestinal metaplasia. Consequently, histological markers that reliably distinguish Barrett's-related oesophageal adenocarcinoma from gastric adenocarcinoma would be useful. Cytokeratins (CK)7 and 20 are cytoplasmic structural proteins with restricted expression that help to determine the origin of many epithelial tumours including those of the gastrointestinal tract. The aim of this study was to determine the utility of co-ordinate CK7 and 20 expression in the distinction of Barrett's-related oesophageal adenocarcinoma from gastric adenocarcinoma arising in a background of intestinal metaplasia. Methods and results: CK7 and 20 immunostaining was performed on randomly selected surgical resection specimens from patients with Barrett's-related oesophageal adenocarcinoma (n = 30) and intestinal type gastric adenocarcinoma (n = 14) arising in a background of intestinal metaplasia. A CK7+ CK20- immunophenotype was demonstrated in 27 of 30 (90%) patients with Barrett's-related oesophageal adenocarcinoma and only three of 14 (21%) gastric adenocarcinomas. The sensitivity, specificity and positive predictive value of a CK7+/20, immunophenotype for a diagnosis of Barrett's-related oesophageal adenocarcinoma was 90%, 79%, and 90%, respectively. Conclusions: A CK7+/20, tumour immunophenotype is associated with Barrett's-related oesophageal adenocarcinoma and may be useful in accurate tumour classification, thus facilitating improving epidemiological evaluation of tumours at the oesophagogastric junction. [source] Short rare MUC6 minisatellites-5 alleles influence susceptibility to gastric carcinoma by regulating gene,HUMAN MUTATION, Issue 8 2010Jeong-Ah Kwon Abstract The human MUC6 gene, which is reported to be expressed in the stomach and gall bladder, is clustered on chromosome 11p15.5 with other secreted mucins. In this study, the genomic structure of MUC6 has been analyzed and five VNTR (minisatellites; MS1,MS5) were identified. These minisatellites were analyzed in genomic DNA extracted from 1,103 controls, 470 gastric cancer patients, and multigenerational families. Five novel minisatellites were found to be polymorphic and transmitted through meiosis by Mendelian inheritance in families. We evaluated allelic variation in these minisatellites to determine if such variation affected the susceptibility to gastric cancer. A significant association (odds ratio [OR]=7.08) between short rare MUC6,MS5 alleles and relative risks were observed for gastric cancer (95% confidence interval [CI], 1.43,35.19; P=0.005). To investigate the function of minisatellite alleles of MUC6,MS5, we examined the effects on gene expression from luciferase reporters when inserted with minisatellites. Interestingly, when the shortest allele (7TR) was inserted in the promoter, the expression level decreased over 20-fold (P<0.001) in normal and cancer cell lines. Furthermore, the cancer-specific rare allele (TR8) also showed decreased expression levels in cancer cells. Therefore, we suggest that the short rare MUC6,MS5 alleles may be related to cancer development by the regulation of MUC6 expression. Hum Mutat 31:1,8, 2010. © 2010 Wiley-Liss, Inc. [source] Rapid detection of metastasis of gastric cancer using reverse transcription loop-mediated isothermal amplificationINTERNATIONAL JOURNAL OF CANCER, Issue 5 2007Daisuke Horibe Abstract Tailor-made surgeries for patients with solid malignancies have been under consideration on the basis of the development of new approaches for minor metastatic foci of malignant tumors. Accurate and reliable methods to detect metastases in biopsy specimens with certain rapidity are essential for the performance of these surgeries. The aim of this study was to develop a rapid and practical method to detect metastasis in specimens from patients with gastric carcinoma with the use of reverse transcription loop-mediated isothermal amplification (RT-LAMP) reaction, a novel technique for detecting mRNA expressions of targeted sequences with high sensitivity, specificity and rapidity under isothermal conditions. RT-LAMP primers to detect cytokeratin19 (CK19) mRNA were generated and 92 lymph nodes (LNs) obtained from 9 patients with gastric cancer were tested for tumor metastases with this technique. Among 92 LNs, 15 were metastasis-positive by routine histopathological examination. RT-LAMP reaction detected CK19 expression in all of the pathologically positive LNs and in 16 of 77 negative LNs. Nested RT-PCR assay for CK19 expression was also performed on 2 of the 9 cases including 32 LNs. The agreement rate of CK19 expression detection by RT-LAMP and RT-PCR analysis was 31/32 (97%). The RT-LAMP technique showed similar sensitivity to detect metastases as nested RT-PCR assay, with a rapidity comparable to that of intraoperative histopathological examination with frozen sectioning and hematoxylin and eosin staining. This method is expected to play an essential role in the performance of tailor-made surgeries in the near future. © 2006 Wiley-Liss, Inc. [source] Selective cyclooxygenase-2 inhibitor downregulates the paracrine epithelial,mesenchymal interactions of growth in scirrhous gastric carcinomaINTERNATIONAL JOURNAL OF CANCER, Issue 3 2007Masakazu Yashiro Abstract The importance of cancer-mesenchymal interactions in the aggressive behavior of scirrhous gastric cancer is supported by experimental and clinical evidences. We have previously reported that gastric fibroblasts secretion of keratinocyte growth factor (KGF) underline the remarkable proliferation of scirrhous gastric cancer cells. Cyclooxygenase-2 (COX-2) is not only expressed in cancer cells, but also in interstitial fibroblasts in gastric carcinoma. To clarify the mechanisms responsible for the antiproliferation effect of COX-2 inhibitors, effect of COX-2 inhibitor on the paracrine epithelial,mesenchymal interactions of growth was examined. Scirrhous gastric cancer cell line, OCUM-2M, gastric fibroblasts, NF-21, and COX-2 inhibitor, JTE-522, were used. Growth-interaction was examined by calculating the number of cancer cells or by measuring [3H] thymidine incorporation of cancer cells. Effect of JTE-522 on KGF expression from NF-21 cells and OCUM-2M cells was analyzed by ELISA and RT-PCR. The conditioned medium from gastric fibroblasts significantly stimulated the growth of scirrhous gastric cancer cells. JTE-522 at the concentrations of 10,5 and 10,6 M significantly decreased the growth-stimulating activity of gastric fibroblasts. JTE-522 reduced the expression of KGF mRNA and the production of KGF from gastric fibroblasts. Oral administration of JTE-522 significantly decreased the size of xenografted tumor coinoculated with OCUM-2M cells and NF-21 cells in nude mice. JTE-522 decreased COX-2 expression and Ki67 labeling index within the coinoculated tumor. These findings suggested that a selective COX-2 inhibitor, JTE-522, downregulates KGF production from gastric fibroblasts, resulting in the inhibition of paracrine epithelial,mesenchymal interactions of proliferation between scirrhous gastric cancer cells and gastric fibroblasts. © 2006 Wiley-Liss, Inc. [source] Quantitative analysis of lymphangiogenic markers for predicting metastasis of human gastric carcinoma to lymph nodesINTERNATIONAL JOURNAL OF CANCER, Issue 3 2005Yasuhiko Kitadai Abstract The spread of tumor cells to regional lymph nodes is an early event of gastric cancer metastasis. In our study, we assessed the expression of lymphangiogenic factors and lymphatic endothelial markers in gastric carcinoma tissues and compared expression levels with the status of lymph node metastasis. We also examined the correlation between lymphatic vessel density (LVD) in primary tumors and lymph node metastasis. Paired biopsy samples (tumor and corresponding normal mucosa) of gastric tissue were obtained from 39 patients with gastric carcinoma. The expression of VEGF-C, VEGF-D, VEGFR-3 and podoplanin mRNAs was assessed by real-time quantitative PCR. The expression of VEGF-C (but not of VEGF-D) was significantly greater in patients with lymph node metastasis than in those without metastasis. The expression of lymphatic endothelial markers VEGFR-3 and podoplanin was also significantly greater in the node-positive group. LVD, as assessed by immunohistochemistry for podoplanin, was correlated with lymph node metastasis. These results indicate that quantitative analysis of lymphangiogenic markers in gastric biopsy specimens may be useful in predicting metastasis of gastric cancer to regional lymph nodes. © 2005 Wiley-Liss, Inc. [source] Overexpression and significance of prion protein in gastric cancer and multidrug-resistant gastric carcinoma cell line SGC7901/ADRINTERNATIONAL JOURNAL OF CANCER, Issue 2 2005Jingping Du Abstract In our previous work, cellular prion protein (PrPc) was identified as an upregulated gene in adriamycin-resistant gastric carcinoma cell line SGC7901/ADR compared to its parental cell line SGC7901. Here we investigate the expression of PrPc in gastric cancer and whether it was involved in multidrug resistance (MDR) of gastric cancer. We demonstrated that PrPc was ubiquitously expressed in gastric cancer cell lines and tissues. PrPc conferred resistance of both P-glycoprotein (P-gp)-related and P-gp-nonrelated drugs on SGC7901, which was accompanied by decreased accumulation and increased releasing amount of adriamycin in PrPc-overexpressing cell line. Inhibition of PrPc expression by antisense or RNAi technology could partially reverse multidrug-resistant phenotype of SGC7901/ADR. PrPc significantly upregulated the expression of the classical MDR-related molecule P-gp but not multidrug resistance associated protein and glutathione S-transferase pi. The PrPc-induced MDR could be partially reversed by P-gp inhibitor verapamil. PrPc could also suppress adriamycin-induced apoptosis and alter the expression of Bcl-2 and Bax, which might be another pathway contributing to PrPc-related MDR. The further study of the biological functions of PrPc may be helpful for understanding the mechanisms of occurrence and development of clinical gastric carcinoma and PrPc-related MDR and developing possible strategies to treat gastric cancer. [source] Downregulation of KiSS-1 expression is responsible for tumor invasion and worse prognosis in gastric carcinomaINTERNATIONAL JOURNAL OF CANCER, Issue 6 2004Dipok Kumar Dhar Abstract KiSS-1 is a promising candidate tumor-suppressor gene and may play a key role in the metastatic cascade. The expression profile and the role of KiSS-1 in cancer progression are largely unknown in most of the cancers, including gastric cancer. In this study, KiSS-1 expression was evaluated by RNase protection assay and localization was done by in situ hybridization in 40 gastric cancers and their adjacent normal gastric mucosa. For comparison with clinicopathologic characteristics and patient prognosis, all patients were divided into 2 groups having high and low KiSS-1 expression by using the median as the cutoff value of KiSS-1 expression as determined by the RNase protection assay. Gastric cancers with low KiSS-1 had frequent venous invasion, distant metastasis and tumor recurrence. Accordingly, patients with low KiSS-1 -expressing tumors had a significantly worse overall and disease-free survival. In multivariate analysis, KiSS-1 became the strongest independent prognostic factor among the conventional prognosticators for gastric cancer patients. Collectively, these findings suggest that KiSS-1 may play a crucial role in gastric cancer invasion and could be a useful target for therapeutic intervention. © 2004 Wiley-Liss, Inc. [source] D2 gastrectomy , a safe operation in experienced hands,INTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 6 2005R.S. Date Summary In the contemporary practice, surgery is the only potentially curative treatment available for gastric cancer. However, there is no consensus on the extent of surgical resection. Advantages of D2 gastrectomy in terms of morbidity, mortality, local recurrence and survival are confirmed in Japanese as well as some European trials. In our hospital, all patients with operable gastric cancer are treated with D2 gastrectomy along with splenectomy and distal pancreatectomy followed by jejunal pouch reconstruction. The study was undertaken to evaluate our practice in terms of postoperative morbidity and mortality. All the patients who had total gastrectomy for gastric carcinoma from January 1995 to December 2000 were included in the study. During this 6-year period, 33 patients underwent potentially curative D2 gastrectomy. Postoperative morbidity and mortality were 18 and 9%, respectively. There were no anastomotic leaks. Three (9%) patients developed dysphasia, of which two (6%) had anastomotic stricture requiring dilatation. We feel D2 gastrectomy with splenectomy and distal pancreatectomy when performed electively is a safe procedure in experienced hands. Oesophago-jejunal anastomosis can be safely performed using circular stapler. [source] Structural characteristics of the cag pathogenicity island and its significance in the classification of Chinese strains of Helicobacter pyloriJOURNAL OF DIGESTIVE DISEASES, Issue 2 2002Jiong LIU OBJECTIVE: To investigate the structural characteristics of the cag pathogenicity island (PAI) and its significance in the classification in Chinese strains of Helicobacter pylori. METHODS: In 107 H. pylori strains isolated from Chinese patients, cagA, cagI, cagII, the cagI,cagII junction and IS605 were studied by using the polymerase chain reaction. RESULTS: The positive rates in Chinese H. pylori strains were 95.3% for cag PAI, 92.5% for cagA, 86.9% for cagI and 66.4% for cagII. There was no statistical difference among H. pylori strains from chronic gastritis, peptic ulcers or gastric carcinoma in the detectable rate of cag PAI, cagA, cagI or cagII (P > 0.05). Of the cag PAI-negative strains, four came from cases of chronic gastritis and one from a patient with cardiac cancer. The products of the cagI,cagII junction were found in only five strains. The continuous cag PAI was much more common in duodenal ulcers than in chronic gastritis (P < 0.01). The positive rates of cagI and cagII were markedly different in chronic gastritis (P < 0.05). One strain of H. pylori tested positive for cagA but negative for other regions of the cag PAI. IS605 was less common in duodenal ulcers than in chronic gastritis (P < 0.05). The amplified fragment of IS605 in one strain from a gastric carcinoma was approximately 1580 bp in size, which was much longer than that in other strains. CONCLUSION: Our results indicate that the cag PAI is very common in Chinese strains of H. pylori. The structural variety of the cag PAI might be related to the virulence of H. pylori. It is suggested that H. pylori may be classified into different virulence groups according to differences in the structure of the cag PAI. [source] Expression of COX-1, COX-2 and inducible nitric oxide synthase in superficial gastritis, mucosal dysplasia and gastric carcinomaJOURNAL OF DIGESTIVE DISEASES, Issue 3 2001Yuqin Luo OBJECTIVE: To investigate the significance of the expression of cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in superficial gastritis, gastric mucosal dysplasia and gastric carcinoma, and to study the relationship between COX-2, iNOS, gastric carcinoma and Helicobacter pylori infection. METHODS: Polyclonal antibodies to COX-1, COX-2 and iNOS were used detect their expression and the status of H. pylori infection in 92 specimens of paraffin-embedded gastric tissue. Of the 92 patients, 33 had superficial gastritis, 30 had gastric mucosal dysplasia and 29 had gastric cancer. Helicobacter pylori was detected by toluidine blue staining. RESULTS: Expression of COX-2 and iNOS in gastric cancer (65.5%, 62.1%) was significantly higher than that in gastritis (18.2%, 18.2%; P < 0.01). Expression of COX-2 and iNOS in gastritis with H. pylori infection was higher than that in gastric mucosal dysplasia with H. pylori infection. The expression of COX-2 and iNOS occurred concomitantly in gastritis, dysplasia and gastric cancer. CONCLUSION: Inflammation and H. pylori infection may be able to stimulate the expression of COX-2 and iNOS, which might be involved in gastric carcinogenesis. [source] Bmi-1 is critical for the proliferation and invasiveness of gastric carcinoma cellsJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 3 2010Wei Li Abstract Background and Aim:, Bmi-1 is a transcriptional repressor belonging to the Polycomb group and is associated with the cell proliferation and carcinogenesis of a variety of human cancers. The level of Bmi-1 expression correlates with the aggressiveness of many cancers, and is considered an important marker for cancer diagnosis. However, its role in gastric carcinoma is unknown. Methods:, We used lentiviral mediated interfering short hairpin RNA to knockdown Bmi-1 expression in gastric carcinoma human gastric cancer cell line (AGS cells), then tested the cell proliferation by MTT assay, rate of colony formation by colony formation assay, cell cycle distribution by fluorescence-activated cell sorting and cell invasiveness by cell invasion assay. To analyze the expression and localization of Bmi-1 in gastric tumor tissues, we further performed the immunohistochemistry analysis on a gastric cancer tissue array. Results:, We found that knocking down Bmi-1 led to slower cell growth, lesser cell invasiveness, decelerated colony formation, and altered cell cycle progression. In addition, a positive relationship between nuclear expression of Bmi-1 and gastric cancer was observed, suggesting that nucleus localization of Bmi-1 in the cells may be a novel marker of gastric cancer. Conclusions:, Our study highlights critical roles for Bmi-1 in gastric cancer, and suggests that Bmi-1 nuclear localization could be an important marker for the diagnosis of gastric cancer. [source] Effect of being overweight on postoperative morbidity and long-term surgical outcomes in proximal gastric carcinoma,JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 3 2009Sung Jin Oh Abstract Background and Aim:, The prevalence of being overweight has risen remarkably in Korea. This study sought to clarify the relationship between being overweight and surgical outcomes in gastric cancer patients. Methods:, A total of 410 patients who underwent curative total gastrectomies with D2 dissection from January 2000 to December 2003 were retrospectively studied from a prospectively designed database. The patients were assigned to two groups based upon their body mass index (BMI): non-overweight, BMI < 25 kg/m2; overweight, BMI , 25 kg/m2. Perioperative surgical outcomes, postoperative morbidity, mortality, recurrence, and prognosis were analyzed. Results:, The overweight group had longer operation time and more postoperative complications than the non-overweight group. The two groups were similar in terms of transfusion volumes, postoperative bowel movement, time to initiation of a soft diet, and postoperative hospital stay. Patterns of recurrence and cumulative survival rates were similar for each group. Multivariate analysis showed that being overweight was not a risk factor for recurrence or poor prognosis. Conclusion:, Although being overweight was associated with increased operation time and higher risk of complications in gastric cancer patients undergoing curative total gastrectomy, it had no effect on recurrence or long-term survival. [source] Overexpression of c-H-ras p21 is correlated with vascular endothelial growth factor expression and neovascularization in advanced gastric carcinoma ,JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 12 2000Young-Bae Kim Abstract Background and Aims ras Gene and its product (p21) have been reported to be associated with vascular endothelial growth factor (VEGF), which is one of the most important angiogenic factors, and tumor-associated angiogenesis. We tried to evaluate the correlation between the expression of c-H-ras gene product p21 and angiogenesis in advanced gastric carcinoma. Methods Immunohistochemical expression of c-H-ras p21 and VEGF was examined in 49 advanced gastric adenocarcinomas. In addition, double immunohistochemical staining was performed using anti-CD34 and anti-Ki-67 antibodies, and the intratumoral microvessel densities and their endothelial proliferative labeling indices were then counted to evaluate the degree of angiogenesis. Results The expression of c-H-ras p21 was demonstrated in 43 out of 49 gastric adenocarcinomas (87.8%). It did not correlate with histologic type, depth of invasion or metastasis. However, the degree of c-H-ras p21 expression was correlated with VEGF. In addition, the degree of c-H-ras p21 expression was correlated with increased intratumoral microvascular density and endothelial proliferative activity. Conclusions We suggest that c-H-ras oncogene product p21 contributes to the upregulation of tumor-associated angiogenesis by the increased production of VEGF in advanced gastric carcinomas. Therefore, treatment involving the targeting of ras oncogene could inhibit solid tumor growth by suppressing tumor-associated angiogenesis. [source] New variations of Epstein,Barr virus-encoded small RNA genes in nasopharyngeal carcinomas, gastric carcinomas, and healthy donors in northern ChinaJOURNAL OF MEDICAL VIROLOGY, Issue 5 2010Yun Wang Abstract It has been generally believed that the Epstein,Barr virus (EBV)-encoded small RNA 1 and 2 (EBER1 and EBER2) genes are conserved as two families that correlated with type 1 (B95-8) and type 2 (AG876 or P3HR-1) EBV strains. EBER polymorphism and its association with EBV-associated disease have not received much attention. To explore the variations of EBER genes in different malignancies and healthy donors, the sequences of EBER genes were analyzed in 154 EBV-positive samples, including 47 nasopharyngeal carcinoma (NPC), 50 EBV-associated gastric carcinoma (EBVaGC) biopsies and 57 throat washing (TW) samples from healthy donors in northern China, where NPC is non-endemic. Three main distinct variants of EBER genes, designated as EB-6m, EB-8m, and EB-10m, were identified. EB-6m had a previously identified EBER sequence identical to P3HR-1 and was found in 33/47 (70.2%) NPC, 48/50 (96.0%) EBVaGC, and 54/57 (94.7%) TW isolates. EB-8m and EB-10m were new EBER variants with more mutations in EBER2 genes. They were found in 13/47 (27.7%) NPC cases, whereas in only 1/50 (2.0%) EBVaGC cases and not found in TW cases. The distributions were significantly different (P,<,0.05). Other five isolates (one NPC, one EBVaGC and three TW cases) showed different sequences and could not be assigned to any of the three groups. Type 1 EBV strains showed heterogeneous in terms of EBER variants. These results suggest that EBER locus can be useful to identify different EBV isolates, and it would be interesting to evaluate the association of EBER polymorphisms with EBV-associated tumors. J. Med. Virol. 82: 829,836, 2010. © 2010 Wiley-Liss, Inc. [source] Pathological prognostic score as a simple criterion to predict outcome in gastric carcinomaJOURNAL OF SURGICAL ONCOLOGY, Issue 1 2010Tadahiro Nozoe MD Abstract Purpose The aim of this study was to establish a simple criterion to predict prognosis of patients with gastric carcinoma. Methods Two hundred four patients with gastric carcinoma, who had been treated with curative resection, were enrolled. One point was added for each category among four pathological factors of depth of tumor, lymph node metastasis, venous invasion, and lymphatic invasion. Pathological Prognostic Score (PPS) was determined by an aggregate of these points for each category. Results There existed a significant difference between survivals of patients with PPS 0 or 1 and 2 or 3 (P,=,0.0002). Similarly, there also existed a significant difference between survivals of patients with PPS 2 or 3 and 4 (P,=,0.010). Conclusions PPS can be quite simple criteria to predict prognosis of gastric carcinoma with a strict stratification. J. Surg. Oncol. 2010;102:11,17. J. Surg. Oncol. 2010;102:73,76. © 2010 Wiley-Liss, Inc. [source] Should direct mesocolon invasion be included in T4 for the staging of gastric cancer?JOURNAL OF SURGICAL ONCOLOGY, Issue 3 2010Jung Hoon Park MD Abstract Background and Objectives One of the sites most frequently invaded by gastric cancer is the mesocolon; however, the UICC does not mention this anatomical site as an adjacent structure involved in gastric cancer. The purpose of this study was to characterize and classify mesocolon invasion from gastric cancer. Methods We examined 806 patients who underwent surgery for advanced gastric carcinoma from 1992 to 2007 at the Department of Surgery, Gangnam Severance Hospital, Korea. Among these, patients who showed macroscopically direct invasion into the mesocolon were compared to other patients with advanced gastric cancer. Results The curability, number and extent of nodal metastasis, and the survival of the mesocolon invasion group were significantly worse than these factors in the T3 group. However, the survival of the mesocolon invasion group after curative resection was much better than that of patients who had incurable factors. Conclusions Mesocolon invasion should be included in T4 for the staging of gastric cancer. J. Surg. Oncol. 2010; 101:205,208. © 2010 Wiley-Liss, Inc. [source] | |||||||||||||||||||||||||||||||