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Sample records for reduce gastric cancer

  1. Gastric cancer

    SciTech Connect

    Douglass, H.O. )

    1988-01-01

    This book contains 10 selections. Some of the titles are: Radiation therapy for gastric cancer; Experimental stomach cancer: Drug selection based on in vitro testing; Western surgical adjuvant trials in gastric cancers: Lessons from current trials to be applied in the future; and Chemotherapy of gastric cancer.

  2. Gastric Cancer: How Can We Reduce the Incidence of this Disease?

    PubMed

    den Hoed, Caroline M; Kuipers, Ernst J

    2016-07-01

    Gastric cancer remains a prevalent disease worldwide with a poor prognosis. Helicobacter pylori plays a major role in gastric carcinogenesis. H. pylori colonization leads to chronic gastritis, which predisposes to atrophic gastritis, intestinal metaplasia, dysplasia, and eventually gastric cancer. Screening, treatment, and prevention of H. pylori colonization can reduce the incidence of gastric cancer. Other interventions that may yield a similar effect, although of smaller magnitude, include promotion of a healthy lifestyle including dietary measures, non-smoking, low alcohol intake, and sufficient physical activity. This chapter reviews interventions that can lead to a decline in gastric cancer incidence in high and low incidence countries. PMID:27184043

  3. Genistein-inhibited cancer stem cell-like properties and reduced chemoresistance of gastric cancer.

    PubMed

    Huang, Weifeng; Wan, Chunpeng; Luo, Qicong; Huang, Zhengjie; Luo, Qi

    2014-01-01

    Genistein, the predominant isoflavone found in soy products, has exerted its anticarcinogenic effect in many different tumor types in vitro and in vivo. Accumulating evidence in recent years has strongly indicated the existence of cancer stem cells in gastric cancer. Here, we showed that low doses of genistein (15 µM), extracted from Millettia nitida Benth var hirsutissima Z Wei, inhibit tumor cell self-renewal in two types of gastric cancer cells by colony formation assay and tumor sphere formation assay. Treatment of gastric cancer cells with genistein reduced its chemoresistance to 5-Fu (fluorouracil) and ciplatin. Further results indicated that the reduced chemoresistance may be associated with the inhibition of ABCG2 expression and ERK 1/2 activity. Furthermore, genistein reduced tumor mass in the xenograft model. Together, genistein inhibited gastric cancer stem cell-like properties and reduced its chemoresistance. Our results provide a further rationale and experimental basis for using the genistein to improve treatment of patients with gastric cancer. PMID:24573253

  4. Genistein-Inhibited Cancer Stem Cell-Like Properties and Reduced Chemoresistance of Gastric Cancer

    PubMed Central

    Huang, Weifeng; Wan, Chunpeng; Luo, Qicong; Huang, Zhengjie; Luo, Qi

    2014-01-01

    Genistein, the predominant isoflavone found in soy products, has exerted its anticarcinogenic effect in many different tumor types in vitro and in vivo. Accumulating evidence in recent years has strongly indicated the existence of cancer stem cells in gastric cancer. Here, we showed that low doses of genistein (15 μM), extracted from Millettia nitida Benth var hirsutissima Z Wei, inhibit tumor cell self-renewal in two types of gastric cancer cells by colony formation assay and tumor sphere formation assay. Treatment of gastric cancer cells with genistein reduced its chemoresistance to 5-Fu (fluorouracil) and ciplatin. Further results indicated that the reduced chemoresistance may be associated with the inhibition of ABCG2 expression and ERK 1/2 activity. Furthermore, genistein reduced tumor mass in the xenograft model. Together, genistein inhibited gastric cancer stem cell-like properties and reduced its chemoresistance. Our results provide a further rationale and experimental basis for using the genistein to improve treatment of patients with gastric cancer. PMID:24573253

  5. NME2 reduces proliferation, migration and invasion of gastric cancer cells to limit metastasis.

    PubMed

    Liu, Yan-fei; Yang, Aijun; Liu, Wei; Wang, Chenyu; Wang, Min; Zhang, Lihan; Wang, Dongcang; Dong, Jing-fei; Li, Min

    2015-01-01

    Gastric cancer is one of the most common malignancies and has a high rate of metastasis. We hypothesize that NME2 (Nucleoside Diphosphate Kinase 2), which has previously been considered as an anti-metastatic gene, plays a role in the invasiveness of gastric cancer cells. Using a tissue chip technology and immunohistochemistry, we demonstrated that NME2 expression was associated with levels of differentiation of gastric cancer cells and their metastasis into the lymph nodes. When the NME2 gene product was over-expressed by ;in vitro stable transfection, cells from BGC823 and MKN45 gastric cancer cell lines had reduced rates of proliferation, migration, and invasion through the collagen matrix, suggesting an inhibitory activity of NME2 in the propagation and invasion of gastric cancer. NME2 could, therefore, severe as a risk marker for gastric cancer invasiveness and a potential new target for gene therapy to enhance or induce NME2 expression. PMID:25700270

  6. [Gastric cancer].

    PubMed

    Belén Fraile, M; Serra Bartual, M; Segarra Sánchez, J; Richart Rufino, M J

    1991-11-01

    Gastric cancer represents a disorder which incidence has come down last years. Its etiology is unknown, but diet is the principal determinant risk of suffering it. Clinic history is not much useful, because in the early stage symptoms can fail and in the late stage are inespecific. Election diagnosis is endoscopy. Surgery is the only curative treatment. By these features, it would be useful to left under vigilance to: a) patients 40 years older with dispepsia; b) patients following gastric operations; c) patients with disorders presenting aclorhidria. The authors report a clinic case that can be of frequent presentation in primary assistance.

  7. Meta-analysis: Does garlic intake reduce risk of gastric cancer?

    PubMed

    Kodali, R T; Eslick, Guy D

    2015-01-01

    In the past 2 decades, various epidemiological studies investigated whether garlic can positively modify the risk of gastric cancer. Garlic contains numerous sulfide compounds, including diallyl trisulfide, which have anticarcinogenic properties. We conducted a meta-analysis to determine if garlic intake reduces the risk of gastric cancer. An electronic search of MEDLINE, PubMed, and EMBASE to June 2014 was completed. There were 14 case control studies, 2 randomized controlled studies, and 1 cohort study that fulfilled our inclusion criteria. We used a random effects model to calculate pooled odds ratios (OR) and 95% confidence intervals (CIs) for risk of gastric cancer with garlic consumption. Meta-analysis of a total of 8,621 cases and 14,889 controls was conducted. Significant variability in duration of garlic intake and reference categories for amount of intake was noted. High, low, and any garlic intake were all associated with reduced risk of gastric cancer. High intake had the most significant risk reduction, OR = 0.49 (95% CI: 0.38-0.62). Heterogeneity was low (I² = 30.85, P = 0.17). A more modest risk reduction was associated with low intake, OR = 0.75 (95% CI: 0.58-0.97). Half of the studies did not separate garlic intake into high or low amounts, intake was only noted as consumption vs. non-consumption. Any amount of consumption still showed a risk reduction similar to low intake, OR = 0.77 (95% CI: 0.60-1.00). Low and any amount of consumption showed moderate heterogeneity (58% and 45%, respectively). Garlic intake appears to be associated with reduced risk of gastric cancer. Further high quality studies are required to confirm this finding and to assess the amount of garlic that needs to be consumed for protective effect.

  8. Stomach (Gastric) Cancer Screening

    MedlinePlus

    ... Treatment Stomach Cancer Prevention Stomach Cancer Screening Research Stomach (Gastric) Cancer Screening (PDQ®)–Patient Version What is ... These are called diagnostic tests . General Information About Stomach (Gastric) Cancer Key Points Stomach cancer is a ...

  9. CCR5 Antagonism by Maraviroc Reduces the Potential for Gastric Cancer Cell Dissemination.

    PubMed

    Mencarelli, Andrea; Graziosi, Luigina; Renga, Barbara; Cipriani, Sabrina; D'Amore, Claudio; Francisci, Daniela; Bruno, Angela; Baldelli, Franco; Donini, Annibale; Fiorucci, Stefano

    2013-12-01

    The chemokine (C-C motif) receptor 5 (CCR5) that belongs to the family of G protein-coupled receptors is exploited by macrophage tropic (R5) human immunodeficiency virus type 1 (HIV-1) to enter cells. Maraviroc, a small molecule CCR antagonist, is used as a part of combination antiretroviral therapy to treat persons infected by R5 HIV-1. CCR5 is expressed in various cancers, and its level of expression is a negative predictor of patients' survival in gastric cancers. Here, we report MKN45, MKN74, and KATOIII cells, three human gastric cancer cell lines with different stages of differentiation, which express CCR5 as detected by flow cytometry and reverse transcription-polymerase chain reaction (RT-PCR), and its ligand RANTES. In vitro experiments demonstrate that CCR5 antagonism reduces gastric cancer cell migration induced by macrophage inflammatory protein 1α (MIP-1α), MIP-1β, and RANTES and adhesion to the ex-planted murine peritoneum. Administration of maraviroc from days 3 to 10 after MKN45 cell inoculation to severe combined immunodeficient (SCID) mice effectively reduced the extent of peritoneal disease and increased survival. Maraviroc treatment also reduced the tumor burden in a xenograft model. Gene expression and RT-PCR analyses revealed that CCR5 antagonism in vivo modulates the expression of genes known for their role in cancer growth including interleukin-10 receptor B; hepatocyte growth factor receptor (MET); the homolog of the atypical cadherin gene, FAT1; Nm23-H1; and lymphotoxin β receptor. In summary, we have shown that CCR5 is mechanistically involved in dissemination of gastric cancer cells, suggesting that small molecule inhibitors of CCR5 might be exploited for their anticancer potential. PMID:24466382

  10. CCR5 Antagonism by Maraviroc Reduces the Potential for Gastric Cancer Cell Dissemination

    PubMed Central

    Mencarelli, Andrea; Graziosi, Luigina; Renga, Barbara; Cipriani, Sabrina; D'Amore, Claudio; Francisci, Daniela; Bruno, Angela; Baldelli, Franco; Donini, Annibale; Fiorucci, Stefano

    2013-01-01

    The chemokine (C-C motif) receptor 5 (CCR5) that belongs to the family of G protein-coupled receptors is exploited by macrophage tropic (R5) human immunodeficiency virus type 1 (HIV-1) to enter cells. Maraviroc, a small molecule CCR antagonist, is used as a part of combination antiretroviral therapy to treat persons infected by R5 HIV-1. CCR5 is expressed in various cancers, and its level of expression is a negative predictor of patients' survival in gastric cancers. Here, we report MKN45, MKN74, and KATOIII cells, three human gastric cancer cell lines with different stages of differentiation, which express CCR5 as detected by flow cytometry and reverse transcription-polymerase chain reaction (RT-PCR), and its ligand RANTES. In vitro experiments demonstrate that CCR5 antagonism reduces gastric cancer cell migration induced by macrophage inflammatory protein 1α (MIP-1α), MIP-1β, and RANTES and adhesion to the ex-planted murine peritoneum. Administration of maraviroc from days 3 to 10 after MKN45 cell inoculation to severe combined immunodeficient (SCID) mice effectively reduced the extent of peritoneal disease and increased survival. Maraviroc treatment also reduced the tumor burden in a xenograft model. Gene expression and RT-PCR analyses revealed that CCR5 antagonism in vivo modulates the expression of genes known for their role in cancer growth including interleukin-10 receptor B; hepatocyte growth factor receptor (MET); the homolog of the atypical cadherin gene, FAT1; Nm23-H1; and lymphotoxin β receptor. In summary, we have shown that CCR5 is mechanistically involved in dissemination of gastric cancer cells, suggesting that small molecule inhibitors of CCR5 might be exploited for their anticancer potential. PMID:24466382

  11. Association of NDRG1 gene promoter methylation with reduced NDRG1 expression in gastric cancer cells and tissue specimens.

    PubMed

    Chang, Xiaojing; Zhang, Shuanglong; Ma, Jinguo; Li, Zhenhua; Zhi, Yu; Chen, Jing; Lu, Yao; Dai, Dongqiu

    2013-05-01

    NDRG1 (N-myc downstream-regulated gene 1) plays a role in cell differentiation and suppression of tumor metastasis. This study aims to determine the expression of NDRG1 mRNA and protein in gastric cancer cell lines and tissue specimens and then assess the possible cause of its aberrant expression. Six gastric cancer cell lines and 20 pairs of normal and gastric cancer tissue samples were used to assess NDRG1 expression using Real-time PCR and Western blot. High-resolution melting analysis (HRM) and methylation-specific PCR (MSP) were performed to detect gene mutation and methylation, respectively, in cell lines and tissues samples. Expression of NDRG1 mRNA and protein was downregulated in gastric cancer cell lines and tissues. Specifically, expression of NDRG1 mRNA and protein was lower in all six gastric cancer cell lines than that of normal gastric cells, while 15 out of 20 cases of gastric cancer tissues had the reduced levels of NDRG1 mRNA and protein. HRM data showed that there was no mutation in NDRG1 gene, but MSP data showed high levels of NDRG1 gene promoter methylation in the CpG islands in both cell lines and tissue samples. Moreover, treatment with the DNA methyltransferase inhibitor 5-Aza-2'-deoxycytidine upregulated NDRG1 expression in gastric cancer HGC27 cells, but not in the histone deacetylase inhibitor trichostatin A-treated HGC27 cells. In conclusion, this study has shown that expression of NDRG1 mRNA and protein was reduced in gastric cancer cell lines and tissues, which is due to methylation of NDRG1 gene promoter. Further study will unearth the clinical significance of the reduced NDRG1 protein in gastric cancer.

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

    PubMed Central

    2013-01-01

    Background 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. Methods 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. Results 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. Conclusions CLDN1 was highly up-regulated in gastric cancer, and CLDN1 expression was independently associated with a poor post

  13. Metformin reduces gastric cancer risk in patients with type 2 diabetes mellitus.

    PubMed

    Tseng, Chin-Hsiao

    2016-08-01

    This retrospective cohort study investigated whether metformin may reduce gastric cancer risk by using the reimbursement databases of the Taiwan's National Health Insurance. Patients with type 2 diabetes diagnosed during 1999-2005 and newly treated with metformin (n=287971, "ever users of metformin") or other antidiabetic drugs (n=16217, "never users of metformin") were followed until December 31, 2011. The effect of metformin (for ever versus never users, and for tertiles of cumulative duration of therapy) was estimated by Cox regression incorporated with the inverse probability of treatment weighting using propensity score. Results showed that the respective numbers of incident gastric cancer in ever and never users were 759 (0.26%) and 89 (0.55%), with respective incidences of 55.26 and 122.53 per 100,000 person-years. The overall hazard ratio (95% confidence intervals) of 0.448 (0.359-0.558) suggested a significantly lower risk among ever users. In tertile analyses, hazard ratios (95% confidence intervals) for the first (<21.47 months), second (21.47-45.97 months) and third (>45.97 months) tertile of cumulative duration was 0.973 (0.773-1.224), 0.422 (0.331-0.537) and 0.120 (0.090-0.161), respectively, while compared to never users. In conclusion, metformin significantly reduces gastric cancer risk, especially when the cumulative duration is more than approximately 2 years. PMID:27587088

  14. Metformin reduces gastric cancer risk in patients with type 2 diabetes mellitus

    PubMed Central

    Tseng, Chin-Hsiao

    2016-01-01

    This retrospective cohort study investigated whether metformin may reduce gastric cancer risk by using the reimbursement databases of the Taiwan's National Health Insurance. Patients with type 2 diabetes diagnosed during 1999-2005 and newly treated with metformin (n=287971, “ever users of metformin”) or other antidiabetic drugs (n=16217, “never users of metformin”) were followed until December 31, 2011. The effect of metformin (for ever versus never users, and for tertiles of cumulative duration of therapy) was estimated by Cox regression incorporated with the inverse probability of treatment weighting using propensity score. Results showed that the respective numbers of incident gastric cancer in ever and never users were 759 (0.26%) and 89 (0.55%), with respective incidences of 55.26 and 122.53 per 100,000 person-years. The overall hazard ratio (95% confidence intervals) of 0.448 (0.359-0.558) suggested a significantly lower risk among ever users. In tertile analyses, hazard ratios (95% confidence intervals) for the first (<21.47 months), second (21.47-45.97 months) and third (>45.97 months) tertile of cumulative duration was 0.973 (0.773-1.224), 0.422 (0.331-0.537) and 0.120 (0.090-0.161), respectively, while compared to never users. In conclusion, metformin significantly reduces gastric cancer risk, especially when the cumulative duration is more than approximately 2 years. PMID:27587088

  15. Gastric cancer and family history

    PubMed Central

    Choi, Yoon Jin; Kim, Nayoung

    2016-01-01

    Gastric cancer is associated with high morbidity and mortality rates worldwide. Identifying individuals at high risk is important for surveillance and prevention of gastric cancer. Having first-degree relatives diagnosed with gastric cancer is a strong and consistent risk factor for gastric cancer, but the pathogenic mechanisms behind this familial aggregation are unclear. Against this background, we reviewed the risk factors for gastric cancer in those with a first-degree relative with gastric cancer, and the possible causes for familial clustering of gastric cancer including bacterial factors, inherited genetic susceptibility, environmental factors or a combination thereof. Among individuals with a family history, current or past Helicobacter pylori infection, having two or more first-degree affected relatives or female gender was associated with an increased risk of developing gastric cancer. To date, no specific single nucleotide polymorphism has been shown to be associated with familial clustering of gastric cancer. H. pylori eradication is the most important strategy for preventing gastric cancer in first-degree relatives of gastric cancer patients, particularly those in their 20s and 30s. Early H. pylori eradication could prevent the progression to intestinal metaplasia and reduce the synergistic effect on gastric carcinogenesis in individuals with both H. pylori infection and a family history. Endoscopic surveillance is also expected to benefit individuals with a family history. Further large-scale, prospective studies are warranted to evaluate the cost-effectiveness and optimal time point for endoscopy in this population. Moreover, genome-wide association studies that incorporate environmental and dietary factors on a ‘big data’ basis will increase our understanding of the pathogenesis of gastric cancer. PMID:27809451

  16. [Gastric cancer in Taiwan].

    PubMed

    Wu, M S; Lin, J T; Lee, W J; Yu, S C; Wang, T H

    1994-09-01

    The study of gastric cancer is important in clinical medicine as well as in public health. Environmental factors play an important role in gastric carcinogenesis and thus primary prevention is feasible after improvement of these factors. The 5-year survival rate of resected early gastric cancer is over 90% and this provides an excellent paradigm for secondary prevention. Though its mortality rate has declined since 1970, gastric cancer remains common and carries a high mortality in Taiwan where about 2,000 patients die of gastric cancer annually. The age-adjusted mortality is 16.54 and 8.16/100,000 for male and female, ranking the third and fourth cancer death respectively. Epidemiologic data disclose a positive association between gastric cancer and some dietary factors in Taiwan. However, the role of Helicobacter pylori infection and hereditary susceptibility should be elucidated in the future. Endoscopy with biopsy is an excellent method of the diagnosis of gastric cancer. However, its invasiveness makes it impractical as a screening tool and thus the proportion of early gastric cancer to gastric cancer remains as low as 30% in most reports. The value of lymph node dissection remains controversial although surgery is one of the most effective methods of eradicating gastric cancer. Overall, the 5 year survival rate is 24.5% to 54%. Laser therapy is usually reserved for patients with high operative risk and specific types of gastric cancer. To improve the survival results, development of a simple and economic screening program based on the epidemiologic results and utilization of noninvasive examinations such as serologic markers to diagnose and treat gastric cancer at its earliest stage deserves further study.

  17. Hereditary Diffuse Gastric Cancer

    MedlinePlus

    ... with the syndrome is recommended. What are the estimated cancer risks associated with HDGC? Not everyone who ... the lifetime risk for diffuse gastric cancer is estimated to be 70% to 80% for men and ...

  18. [Intermediate gastric cancer].

    PubMed

    Fontán, A N; Marzano, C A; Martínez, M M; Palau, G; Rubio, H H

    1980-01-01

    Gastric Cancer comprises two basic types: Advanced Gastric Cancer (A.G.C.) and Early Gastric Cancer (E.G.C.). A.G.C. extends beyond the proper muscle layer with a 5 to 17%, five years survival rate after surgery. E.G.C. does not extend beyond the submucosa (with or without metastasis to regional lymph nodes) and has a 80 - 95% five years survival rate. Intermediate Gastric Cancer, PM G.C. (Gastric cancer of the proper muscle layer) does not surpass the proper muscle layer and offers a five years life expectance of near 60% after adequate surgical treatment, with peculiar features in radiology, endoscopy and evolutivity. We report a case of PM G.C., "depressed" and "protruded". The proper muscle layer was invaded by the depressed lesion". Both lesions were continguous.

  19. Etiology and Prevention of Gastric Cancer

    PubMed Central

    Cheng, Xiao Jiao; Lin, Jia Cheng; Tu, Shui Ping

    2016-01-01

    Background Gastric cancer is a heterogeneous malignant disease associated with environmental and genetic predisposing factors. While gastric cancer incidence and mortality fell greatly globally over the past decades, it remains the fourth cause of cancer-related death worldwide. Thus, prevention of gastric cancer is still a major strategy for improvement of gastric cancer prognosis. Summary Helicobacter pylori infection has been demonstrated to be a major risk factor for the development of gastric cancer. Unhealthy diet and lifestyle, including high-salt food, smoking and drinking, are able to induce genotypic and phenotypic transformation of gastric epithelial cells. Gene mutations (such as E-cadherin) in stomach epithelial cells are major genetic causes for gastric cancer. The eradication of H. pylori has been demonstrated to be an effective approach for primary prevention of gastric cancer. Increased intake of a diet rich in vegetables and fresh fruits as well as smoking cessation have been shown to reduce the incidence of gastric cancer. The secondary prevention strategy is to screen premalignant gastric lesions by endoscopy. Biomarker tests are also reliable methods to identify gastric precancerous lesions. Endoscopy screening is still the gold standard for diagnosis of gastric cancer. Key Message H. pylori infection, a diet rich in salted and/or smoked food and red meat, as well as gene mutations are major risk factors for the development of gastric cancer. Practical Implications The eradication of H. pylori is a major primary preventive strategy of gastric cancer. A healthy lifestyle, including increased intake of a diet rich in fruit and vegetables, reduced intake of salted and smoked food and red meat, a reduction of alcohol intake as well as smoking cessation will be effective approaches for the prevention of gastric cancer. PMID:27722154

  20. Ramucirumab for gastric cancer.

    PubMed

    Shitara, Kohei; Ohtsu, Atsushi

    2015-02-01

    In recent years, various molecular target agents have been investigated for gastric cancer. VEGF is one of the most potent angiogenic factors and is a signaling molecule secreted by many solid tumors. High VEGF expression is one of the characteristic features of gastric carcinomas, thus targeting VEGF is considered a promising strategy for gastric cancer. Ramucirumab, an anti-VEGF receptor antibody, has proven to be effective for previously treated advanced gastric cancer. Details of ramucirumab, including two pivotal Phase III studies, will be discussed in this review. Ramucirumab, with or without chemotherapy, improved survival in gastric cancer after previous systemic chemotherapy, thus becoming the standard of care for this patient population. Optimal timing of ramucirumab use and adequate biomarkers for patient selection as well as mechanism of resistance should be explored in future research.

  1. Statins Attenuate Helicobacter pylori CagA Translocation and Reduce Incidence of Gastric Cancer: In Vitro and Population-Based Case-Control Studies.

    PubMed

    Lin, Chun-Jung; Liao, Wei-Chih; Lin, Hwai-Jeng; Hsu, Yuan-Man; Lin, Cheng-Li; Chen, Yu-An; Feng, Chun-Lung; Chen, Chih-Jung; Kao, Min-Chuan; Lai, Chih-Ho; Kao, Chia-Hung

    2016-01-01

    Gastric cancer is the second leading cause of cancer-related death worldwide. The correlation of Helicobacter pylori and the etiology of gastric cancer was substantially certain. Cholesterol-rich microdomains (also called lipid rafts), which provide platforms for signaling, are associated with H. pylori-induced pathogenesis leading to gastric cancer. Patients who have been prescribed statins, inhibitors of 3-hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA) reductase, have exhibited a reduced risk of several types of cancer. However, no studies have addressed the effect of statins on H. pylori-associated gastric cancer from the antineoplastic perspective. In this study, we showed that treatment of gastric epithelial cells with simvastatin reduced the level of cellular cholesterol and led to attenuation of translocation and phosphorylation of H. pylori cytotoxin-associated gene A (CagA), which is recognized as a major determinant of gastric cancer development. Additionally, a nationwide case-control study based on data from the Taiwanese National Health Insurance Research Database (NHIRD) was conducted. A population-based case-control study revealed that patients who used simvastatin exhibited a significantly reduced risk of gastric cancer (adjusted odds ratio (OR) = 0.76, 95% confidence interval (CI) = 0.70-0.83). In patients exhibiting H. pylori infection who were prescribed simvastatin, the adjusted OR for gastric cancer was 0.25 (95% CI = 0.12-0.50). Our results combined an in vitro study with a nationwide population analysis reveal that statin use might be a feasible approach to prevent H. pylori-associated gastric cancer.

  2. Statins Attenuate Helicobacter pylori CagA Translocation and Reduce Incidence of Gastric Cancer: In Vitro and Population-Based Case-Control Studies

    PubMed Central

    Hsu, Yuan-Man; Lin, Cheng-Li; Chen, Yu-An; Feng, Chun-Lung; Chen, Chih-Jung; Kao, Min-Chuan; Lai, Chih-Ho; Kao, Chia-Hung

    2016-01-01

    Gastric cancer is the second leading cause of cancer-related death worldwide. The correlation of Helicobacter pylori and the etiology of gastric cancer was substantially certain. Cholesterol-rich microdomains (also called lipid rafts), which provide platforms for signaling, are associated with H. pylori-induced pathogenesis leading to gastric cancer. Patients who have been prescribed statins, inhibitors of 3-hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA) reductase, have exhibited a reduced risk of several types of cancer. However, no studies have addressed the effect of statins on H. pylori-associated gastric cancer from the antineoplastic perspective. In this study, we showed that treatment of gastric epithelial cells with simvastatin reduced the level of cellular cholesterol and led to attenuation of translocation and phosphorylation of H. pylori cytotoxin-associated gene A (CagA), which is recognized as a major determinant of gastric cancer development. Additionally, a nationwide case-control study based on data from the Taiwanese National Health Insurance Research Database (NHIRD) was conducted. A population-based case-control study revealed that patients who used simvastatin exhibited a significantly reduced risk of gastric cancer (adjusted odds ratio (OR) = 0.76, 95% confidence interval (CI) = 0.70–0.83). In patients exhibiting H. pylori infection who were prescribed simvastatin, the adjusted OR for gastric cancer was 0.25 (95% CI = 0.12–0.50). Our results combined an in vitro study with a nationwide population analysis reveal that statin use might be a feasible approach to prevent H. pylori-associated gastric cancer. PMID:26730715

  3. Occupation and gastric cancer

    PubMed Central

    Raj, A; Mayberry, J; Podas, T

    2003-01-01

    Gastric cancer is a cause of significant morbidity and mortality. There are several risk factors, with occupation emerging as one of these. There is considerable evidence that occupations in coal and tin mining, metal processing, particularly steel and iron, and rubber manufacturing industries lead to an increased risk of gastric cancer. Other "dusty" occupations—for example, wood processing, or work in high temperature environments have also been implicated but the evidence is not strong. The mechanism of pathogenesis of gastric cancer is unclear and the identification of causative agents can be difficult. Dust is thought to be a contributor to the pathological process, but well known carcinogens such as N-nitroso compounds have been detected in some environments. Further research on responsible agents is necessary and screening for detection of precursor gastric cancer lesions at the workplace merits consideration. PMID:12782770

  4. Gastric cancer and trastuzumab: first biologic therapy in gastric cancer

    PubMed Central

    Gunturu, Krishna S.; Woo, Yanghee; Beaubier, Nike; Remotti, Helen E.

    2013-01-01

    Gastric cancer remains difficult to cure and has a poor overall prognosis. Chemotherapy and multimodality therapy has shown some benefit in the treatment of gastric cancer. Current therapies for gastric cancer have their limitations; thus, we are in need of newer treatment options including targeted therapies. Here, we review the biologic therapy with trastuzumab in human epidermal growth factor receptor 2 (HER2)+ gastric cancer. PMID:23450234

  5. General Information about Gastric Cancer

    MedlinePlus

    ... Research Gastric Cancer Treatment (PDQ®)–Patient Version General Information About Gastric Cancer Go to Health Professional Version ... the PDQ Adult Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

  6. [Tumor markers in gastric cancer].

    PubMed

    Ohkura, Hisanao

    2002-04-01

    There are two markers, pepsinogen isoenzymes and antibody against Helicobactor pyroli, for screening of high-risk group for gastric cancer. Most of markers are used in diagnosis, staging, monitoring and differentiating subgroups of gastric cancer. Markers in ascitic fluid are used for diagnosing peritoneal invasion of gastric cancer. PMID:11977555

  7. [Helicobacter pylori and gastric cancer].

    PubMed

    León-Barúa, R; Recavarren-Arce, S; Berendson, R; Gilman, R H

    1995-01-01

    A review is done on the evidence in favor of a link between Helicobacter pylori infection and gastric cancer of the intestinal type. In countries at high risk of gastric cancer, like Perú, Hp infection begins early in life and is highly frequent and persistent. When Hp colonizes the gastric mucosa, it causes active chronic gastritis. Initially, the gastritis is of the superficial type. With time, and probably as a result of the concurrent action of nutritional, epidemiologic and immunologic modulating factors, chronic superficial gastritis may give rise to a progressive gastric pathology that leads to gastric premalignant lesions (chronic atrophic gastritis, intestinal metaplasia and dysplasia of the gastric mucosa) and increases the predisposition to gastric cancer. The principal modulating factors are described. The epidemiology of gastric premalignant lesions in Perú is also described. Finally, a discussion is done on the effect that eradication of Hp infection might have on the prevalence of gastric cancer.

  8. Clinical epidemiology of gastric cancer

    PubMed Central

    Ang, Tiing Leong; Fock, Kwong Ming

    2014-01-01

    Gastric cancer is the second leading cause of cancer-related mortality and the fourth most common cancer globally. There are, however, distinct differences in incidence rates in different geographic regions. While the incidence rate of gastric cancer has been falling, that of gastric cardia cancers is reportedly on the rise in some regions. Helicobacter pylori (H. pylori) infection is a major risk factor of non-cardia gastric cancer, and data has emerged concerning the role of H. pylori eradication for primary prevention of gastric cancer. Dietary, lifestyle and metabolic factors have also been implicated. Although addressing these other factors may contribute to health, the actual impact in terms of cancer prevention is unclear. Once irreversible histological changes have occurred, endoscopic surveillance would be necessary. A molecular classification system offers hope for molecularly tailored, personalised therapies for gastric cancer, which may improve the prognosis for patients. PMID:25630323

  9. Gastric cancer review

    PubMed Central

    Carcas, Lauren Peirce

    2014-01-01

    Gastric cancer is an aggressive disease that continues to have a daunting impact on global health. Despite an overall decline in incidence over the last several decades, gastric cancer remains the fourth most common type of cancer and is the second leading cause of cancer-related death worldwide. This review aims to discuss the global distribution of the disease and the trend of decreasing incidence of disease, delineate the different pathologic subtypes and their immunohistochemical (IHC) staining patterns and molecular signatures and mutations, explore the role of the pathogen H. pylori in tumorgenesis, discuss the increasing incidence of the disease in the young, western populations and define the role of biologic agents in the treatment of the disease. PMID:25589897

  10. Surrounding Gastric Mucosa Findings Facilitate Diagnosis of Gastric Neoplasm as Gastric Adenoma or Early Gastric Cancer

    PubMed Central

    Miike, Tadashi; Yamamoto, Shojiro; Miyata, Yoshifumi; Hirata, Tomoya; Noda, Yuko; Noda, Takaho; Suzuki, Sho; Takeda, Sachiko; Natsuda, Shuichiro; Sakaguchi, Mai; Maemura, Kosuke; Hashimoto, Kanna; Yamaji, Takumi; Abe, Hiroo; Iwakiri, Hisayoshi; Tahara, Yoshihiro; Hasuike, Satoru; Nagata, Kenji; Kitanaka, Akira; Shimoda, Kazuya

    2016-01-01

    Background and Aim. It is difficult to master the skill of discriminating gastric adenoma from early gastric cancer by conventional endoscopy or magnifying endoscopy combined with narrow-band imaging, because the colors and morphologies of these neoplasms are occasionally similar. We focused on the surrounding gastric mucosa findings in order to determine how to discriminate between early gastric cancer and gastric adenoma by analyzing the characteristics of the gastric background mucosa. Methods. We retrospectively examined 146 patients who underwent endoscopic submucosal dissection for gastric neoplasm between October 2009 and January 2015. The boundary of atrophic gastritis was classified endoscopically according to the Kimura-Takemoto classification system. Of 146 lesions, 63 early gastric cancers and 21 gastric adenomas were ultimately evaluated and assessed. Results. Almost all gastric adenomas were accompanied by open-type gastritis, whereas 47 and 16 early gastric cancers were accompanied by open-type and closed-type gastritis, respectively (p = 0.037). Conclusions. The evaluation of the boundary of atrophic gastritis associated with gastric neoplasms appears to be useful for discrimination between early gastric cancer and gastric adenoma. When gastric neoplasm is present in the context of surrounding localized gastric atrophy, gastric cancer is probable but not certain. PMID:26858751

  11. Molecular mechanisms of chemoresistance in gastric cancer.

    PubMed

    Shi, Wen-Jia; Gao, Jin-Bo

    2016-09-15

    Gastric cancer is the fourth most common cancer and the second leading cause of cancer deaths worldwide. Chemotherapy is one of the major treatments for gastric cancer, but drug resistance limits the effectiveness of chemotherapy, which results in treatment failure. Resistance to chemotherapy can be present intrinsically before the administration of chemotherapy or it can develop during chemotherapy. The mechanisms of chemotherapy resistance in gastric cancer are complex and multifactorial. A variety of factors have been demonstrated to be involved in chemoresistance, including the reduced intracellular concentrations of drugs, alterations in drug targets, the dysregulation of cell survival and death signaling pathways, and interactions between cancer cells and the tumor microenvironment. This review focuses on the molecular mechanisms of chemoresistance in gastric cancer and on recent studies that have sought to overcome the underlying mechanisms of chemoresistance. PMID:27672425

  12. Molecular mechanisms of chemoresistance in gastric cancer

    PubMed Central

    Shi, Wen-Jia; Gao, Jin-Bo

    2016-01-01

    Gastric cancer is the fourth most common cancer and the second leading cause of cancer deaths worldwide. Chemotherapy is one of the major treatments for gastric cancer, but drug resistance limits the effectiveness of chemotherapy, which results in treatment failure. Resistance to chemotherapy can be present intrinsically before the administration of chemotherapy or it can develop during chemotherapy. The mechanisms of chemotherapy resistance in gastric cancer are complex and multifactorial. A variety of factors have been demonstrated to be involved in chemoresistance, including the reduced intracellular concentrations of drugs, alterations in drug targets, the dysregulation of cell survival and death signaling pathways, and interactions between cancer cells and the tumor microenvironment. This review focuses on the molecular mechanisms of chemoresistance in gastric cancer and on recent studies that have sought to overcome the underlying mechanisms of chemoresistance.

  13. Molecular mechanisms of chemoresistance in gastric cancer

    PubMed Central

    Shi, Wen-Jia; Gao, Jin-Bo

    2016-01-01

    Gastric cancer is the fourth most common cancer and the second leading cause of cancer deaths worldwide. Chemotherapy is one of the major treatments for gastric cancer, but drug resistance limits the effectiveness of chemotherapy, which results in treatment failure. Resistance to chemotherapy can be present intrinsically before the administration of chemotherapy or it can develop during chemotherapy. The mechanisms of chemotherapy resistance in gastric cancer are complex and multifactorial. A variety of factors have been demonstrated to be involved in chemoresistance, including the reduced intracellular concentrations of drugs, alterations in drug targets, the dysregulation of cell survival and death signaling pathways, and interactions between cancer cells and the tumor microenvironment. This review focuses on the molecular mechanisms of chemoresistance in gastric cancer and on recent studies that have sought to overcome the underlying mechanisms of chemoresistance. PMID:27672425

  14. Primary gastric tuberculosis mimicking gastric cancer

    PubMed Central

    Eray, İsmail Cem; Rencüzoğulları, Ahmet; Yalav, Orçun; Dalcı, Kubilay; Kakil, Erdem; Bağır, Emine; Parsak, Cem Kaan

    2015-01-01

    A 42-year-old female patient with no previous known diseases who had complaints of postprandial epigastric pain and weight loss and who could not be diagnosed by endoscopic biopsy, although gastric cancer was suspected radiologically and endoscopically, was diagnosed with primary gastric tuberculosis by laparotomy and frozen section. Following anti-tuberculosis treatment, a complete clinical, radiological, and endoscopic response was achieved. PMID:26504425

  15. Drugs Approved for Stomach (Gastric) Cancer

    MedlinePlus

    ... Professionals Questions to Ask about Your Treatment Research Drugs Approved for Stomach (Gastric) Cancer This page lists ... stomach (gastric) cancer that are not listed here. Drugs Approved for Stomach (Gastric) Cancer Cyramza (Ramucirumab) Docetaxel ...

  16. Not all gastric masses are gastric cancer.

    PubMed

    Del Rosario, Michael; Tsai, Henry

    2016-01-01

    Lung cancer metastasising to the gastrointestinal tract normally does not occur. However, as clinicians, we must be aware that lung adenocarcinoma, as in all cancers, can and will metastasise to any part of the body. We describe a case of a patient with a presumed primary gastric adenocarcinoma who presented with shortness of breath due to pleural effusion. Pathology from the pleural effusion was positive for primary lung adenocarcinoma. Further investigation revealed that the patient's gastric mass was misdiagnosed as gastric adenocarcinoma. We correctly diagnosed the mass as metastatic lung adenocarcinoma. This was very significant because the patient was transitioning to palliative care with possible tube feeding. After the correct diagnosis, her management drastically changed and her health improved. Clinical, pathological and medical management of lung cancer metastasis to the stomach are discussed. PMID:26976833

  17. Reduced expression of SET7/9, a histone mono-methyltransferase, is associated with gastric cancer progression

    PubMed Central

    Akiyama, Yoshimitsu; Koda, Yuki; Byeon, Sun-ju; Shimada, Shu; Nishikawaji, Taketo; Sakamoto, Ayuna; Chen, Yingxuan; Kojima, Kazuyuki; Kawano, Tatsuyuki; Eishi, Yoshinobu; Deng, Dajun; Kim, Woo Ho; Zhu, Wei-Guo; Yuasa, Yasuhito; Tanaka, Shinji

    2016-01-01

    SET7/9, a histone methyltransferase, has two distinct functions for lysine methylation. SET7/9 methylates non-histone proteins, such as p53, and participates in their posttranslational modifications. Although SET7/9 transcriptionally activate the genes via H3K4 mono-methylation, its target genes are poorly understood. To clarify whether or not SET7/9 is related to carcinogenesis, we studied alterations of SET7/9 in gastric cancers (GCs). Among the 376 primary GCs, 129 cases (34.3%) showed loss or weak expression of SET7/9 protein compared to matched non-cancerous tissues by immunohistochemistry. Reduced SET7/9 expression was significantly correlated with clinical aggressiveness and worse prognosis. Knockdown of SET7/9 in GC cells markedly increased cell proliferation, migration and invasion. Expression of SREK1IP1, PGC and CCDC28B were inhibited in GC cells with SET7/9 knockdown, while matrix metalloproteinase genes (MMP1, MMP7 and MMP9) were activated. SET7/9 bound and mono-methylated H3K4 at the region of the approximately 4-6 kb upstream from the SREK1IP1 transcriptional start site and the promoters of PGC and CDC28B. Cell proliferation, migration and invasion, and expression of three MMPs were increased in GC cells with SREK1IP knockdown, which were similar to those of SET7/9 knockdown. These data suggest that SET7/9 has tumor suppressor functions, and loss of SET7/9 may contribute to gastric cancer progression. PMID:26701885

  18. Risks of Stomach (Gastric) Cancer Screening

    MedlinePlus

    ... Treatment Stomach Cancer Prevention Stomach Cancer Screening Research Stomach (Gastric) Cancer Screening (PDQ®)–Patient Version What is ... These are called diagnostic tests . General Information About Stomach (Gastric) Cancer Key Points Stomach cancer is a ...

  19. Epigenetic mechanisms in gastric cancer.

    PubMed

    Gigek, Carolina Oliveira; Chen, Elizabeth Suchi; Calcagno, Danielle Queiroz; Wisnieski, Fernanda; Burbano, Rommel Rodriguez; Smith, Marilia Arruda Cardoso

    2012-06-01

    Cancer is considered one of the major health issues worldwide, and gastric cancer accounted for 8% of total cases and 10% of total deaths in 2008. Gastric cancer is considered an age-related disease, and the total number of newly diagnosed cases has been increasing as a result of the higher life expectancy. Therefore, the basic mechanisms underlying gastric tumorigenesis is worth investigation. This review provides an overview of the epigenetic mechanisms, such as DNA methylation, histone modifications, chromatin remodeling complex and miRNA, involved in gastric cancer. As the studies in gastric cancer continue, the mapping of an epigenome code is not far for this disease. In conclusion, an epigenetic therapy might appear in the not too distant future.

  20. Mouse Models of Gastric Cancer

    PubMed Central

    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

  1. Epidemiology of Helicobacter pylori and gastric cancer.

    PubMed

    Kikuchi, Shogo

    2002-01-01

    Findings in epidemiological studies of the relationship between Helicobacter pylori and gastric cancer have been inconsistent: many studies have yielded a positive relationship, whereas several studies have shown no relationship. The inconsistency arises because of the occurrence of seroreversion during the period between the time that H. pylori exerts a carcinogenic effect and the time of blood sampling. When this seroreversion is taken into account, there is an epidemiologically positive association between H. pylori status and the risk for gastric cancer. In addition to the epidemiological evidence, experimental studies using Mongolian gerbils have shown that H. pylori infection elevates the risk for gastric cancer. It is concluded that H. pylori is a causal factor for gastric cancer. In the creation of preventive strategies against gastric cancer by the eradication of H. pylori, determination of the time at which H. pylori plays a role as a carcinogen is important. Three hypotheses have been proposed in regard to this timing: that H. pylori infection in childhood or the teenage years acts as a factor that produces precancerous lesions with irreversible damage in the gastric mucosa, that in adulthood it acts as an initiator, and also in adulthood, that it acts as a promoter. As these hypotheses are not mutually exclusive, the extent to which each hypothesis plays a part in explaining gastric carcinogenesis should be evaluated. Only a small proportion of subjects infected with H. pylori have gastric cancer during their lifetime. Interleukin-1 polymorphism, a host factor, and CagA, a virulence factor of H. pylori, are suspected to be risk factors for gastric cancer in subjects with H. pylori infection. Dietary factors, especially vitamin C, and patterns of precancerous lesions also seem to influence the relationship between H. pylori and gastric cancer. H. pylori seems to reduce the risk for esophageal and for some gastric cardia adenocarcinomas. This finding, as

  2. Mortality reduction from gastric cancer by endoscopic and radiographic screening.

    PubMed

    Hamashima, Chisato; Shabana, Michiko; Okada, Katsuo; Okamoto, Mikizo; Osaki, Yoneatsu

    2015-12-01

    To evaluate mortality reduction from gastric cancer by endoscopic screening, we undertook a population-based cohort study in which both radiographic and endoscopic screenings for gastric cancer have been carried out. The subjects were selected from the participants of gastric cancer screening in two cities in Japan, Tottori and Yonago, from 2007 to 2008. The subjects were defined as participants aged 40-79 years who had no gastric cancer screening in the previous year. Follow-up of mortality was continued from the date of the first screening to the date of death or up to December 31, 2013. A Cox proportional hazards model was used to estimate the relative risk (RR) of gastric cancer incidence, gastric cancer death, all cancer deaths except gastric cancer death, and all-causes death except gastric cancer death. The number of subjects selected for endoscopic screening was 9950 and that for radiographic screening was 4324. The subjects screened by endoscopy showed a 67% reduction of gastric cancer compared with the subjects screened by radiography (adjusted RR by sex, age group, and resident city = 0.327; 95% confidence interval [CI], 0.118-0.908). The adjusted RR of endoscopic screening was 0.968 (95%CI, 0.675-1.387) for all cancer deaths except gastric cancer death, and 0.929 (95%CI, 0.740-1.168) for all-causes death except gastric cancer death. This study indicates that endoscopic screening can reduce gastric cancer mortality by 67% compared with radiographic screening. This is consistent with previous studies showing that endoscopic screening reduces gastric cancer mortality.

  3. Pharmacokinetics and pharmacogenomics in gastric cancer chemotherapy.

    PubMed

    Nishiyama, Masahiko; Eguchi, Hidetaka

    2009-05-20

    Despite extensive efforts, treatment of gastric cancer by chemotherapy, the globally accepted standard, is yet undetermined, and uncertainty remains regarding the optimal regimen. Recent introduction of active "new generation agents" offers hope for improving patient outcomes. Current chemotherapeutic trials provided several regimens that may become a possible standard treatment, including docetaxel/cisplatin/5-FU (TCF) and cisplatin/S-1 for advanced and metastatic cancer and S-1 monotherapy in the adjuvant setting. Along with the development of novel active regimens, individual optimization of cancer chemotherapy has been attempted in order to reduce toxicity and enhance tumor response. Unlike the rare and limited contribution of pharmacokinetic studies, pharmacogenomic studies are increasing the potential to realize the therapeutics against gastric cancer. Despite the limited data, pharmacogenomics in gastric cancer have provided a number of putative biomarkers for the prediction of tumor response to chemotherapies and of toxicity.

  4. Photodynamic therapy of gastric cancer

    NASA Astrophysics Data System (ADS)

    Kharnas, Sergey S.; Kuzin, N. M.; Zavodnov, Victor Y.; Sclyanskaya, Olga A.; Linkov, Kirill G.; Loschenov, Victor B.; Meerovich, Gennadii A.; Torshina, Nadezgda L.; Stratonnikov, Alexander A.; Steiner, Rudolf W.

    1996-01-01

    Photodynamic therapy (PDT) with the use of laser endoscopic spectrum analyzer (LESA-5), the spectral-analyzing video-imaging system, Kr laser and various types of catheters for different tumor localizations, and Phthalocyanine aluminum photosensitizers in patients with gastric cancer was discussed. PDT was carried out in fifteen patients with gastric cancer. There were the following indications for PDT: early gastric cancer (3 patients), malignant stenosis of the cardia or pyloric portion of the stomach (4 patients), cancer of gastric stump with stenosis of gastrojejunal anastomosis (1 patient), preoperative treatment of patients with large but probably resectable gastric tumor size (7 patients). Usually we used 3 - 4 seances of laser treatment 10 - 30 minutes long. Concentration of photosensitizer in normal and malignant tissue was controlled by LESA-5. Treatment was monitored by spectral-analyzing video- imaging system in fluorescent light. The results show high efficiency of PDT especially in patients with early gastric cancer (necrosis of all tumor mass, i.e. complete regression of tumor). For all other patients we obtained partial regression of gastric cancer.

  5. Gastric cancer pathogenesis.

    PubMed

    Berger, Hilmar; Marques, Miguel S; Zietlow, Rike; Meyer, Thomas F; Machado, Jose C; Figueiredo, Ceu

    2016-09-01

    Gastric cancer (GC) results from a multistep process that is influenced by Helicobacter pylori infection, genetic susceptibility of the host, as well as of other environmental factors. GC results from the accumulation of numerous genetic and epigenetic alterations in oncogenes and tumor suppressor genes, leading to dysregulation of multiple signaling pathways, which disrupt the cell cycle and the balance between cell proliferation and cell death. For this special issue, we have selected to review last year's advances related to three main topics: the cell of origin that initiates malignant growth in GC, the mechanisms of direct genotoxicity induced by H. pylori infection, and the role of aberrantly expressed long noncoding RNAs in GC transformation. The understanding of the molecular basis of GC development is of utmost importance for the identification of novel targets for GC prevention and treatment. PMID:27531537

  6. DBGC: A Database of Human Gastric Cancer.

    PubMed

    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

  7. DBGC: A Database of Human Gastric Cancer.

    PubMed

    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.

  8. [Research progression of translational medicine in gastric cancer].

    PubMed

    Li, Maoran; Zhao, Gang; Zhu, Chunchao

    2014-02-01

    Gastric cancer is one of the most common malignant tumors which is a great threat to human health. In recent years, the reform of surgical mordalities and the optimization of radiation and chemotherapy is still far from reducing morbidity and mortality of gastric cancer. As a new research pattern, translational medicine has emerged in various clinical subjects, which leads to remarkable effects. In this paper, the definition and development of translational medicine, molecular markers and drug treatment of gastric cancer will be discussed and the feasibility of translational medicine in the treatment of gastric cancer will be explained. In our opinion, the intervention of translational medicine could change the current situation that scientific researches is severely disconnected with clinical practice and increase the detection rate of gastric cancer and the effective rate of adjuvant therapy after surgery to improve the prognosis of patients with gastric cancer.

  9. Treatment modalities for early gastric cancer

    PubMed Central

    Espinel, Jesús; Pinedo, Eugenia; Ojeda, Vanesa; del Rio, Maria Guerra

    2015-01-01

    Different treatment modalities have been proposed in the treatment of early gastric cancer (EGC). Endoscopic resection (ER) is an established treatment that allows curative treatment, in selected cases. In addition, ER allows for an accurate histological staging, which is crucial when deciding on the best treatment option for EGC. Recently, endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) have become alternatives to surgery in early gastric cancer, mainly in Asian countries. Patients with “standard” criteria can be successfully treated by EMR techniques. Those who meet “expanded” criteria may benefit from treatment by ESD, reducing the need for surgery. Standardized ESD training system is imperative to promulgate effective and safe ESD technique to practices with limited expertise. Although endoscopic resection is an option in patients with EGC, surgical treatment continues to be a widespread therapeutic option worldwide. In this review we tried to point out the treatment modalities for early gastric cancer. PMID:26380052

  10. [Helicobacter pylori and gastric cancer].

    PubMed

    Ramírez Ramos, Alberto; Sánchez Sánchez, Rolando

    2008-01-01

    Since its discovery and identification in gastric tissue by Marshall and Warren in 1983, our knowledge about the effects of Helicobacter pylori infection has grown considerably. Its role in the multifactorial pathology of peptic ulcer disease (gastrodudodenal ulcer disease), gastric adenocarcinoma, and MALT lymphoma is now widely accepted while its involvement in extraintestinal disease is still controversial.The correlation between the colonization of the stomach by H. pylori and gastric lymphoma has been demonstrated in multiple studies. Between 65 and 80% of distal gastric adenocarcinomas are attributed to H. pylori infection. However, gastric carcinogenesis cannot be explained by H. pylori infection alone. Among those individuals infected by this bacteria, only a small percentage (2-5%) ever develops gastric cancer, the majority exhibit benign lesions. There is a wide individual variation in the outcome of this infection in patients. This individual and population specific variation is due to the intricate relationship between genetics, the environment, bacterial virulence, diet, and socio-economic status and it explains the multiple outcomes of this infection. In this article, we conduct a review of the widely accepted theories regarding gastric cancer, Helicobacter pylori, the correlations and enigmas between them, the reported geographical variations, and the various proposed hypotheses on the carcinogenic mechanism of Helicobacter pylori.

  11. Diagnosis and Management of High Risk Group for Gastric Cancer

    PubMed Central

    Yoon, Hyuk; Kim, Nayoung

    2015-01-01

    Gastric cancer is associated with high morbidity and mortality worldwide. To reduce the socioeconomic burden related to gastric cancer, it is very important to identify and manage high risk group for gastric cancer. In this review, we describe the general risk factors for gastric cancer and define high risk group for gastric cancer. We discuss strategies for the effective management of patients for the prevention and early detection of gastric cancer. Atrophic gastritis (AG) and intestinal metaplasia (IM) are the most significant risk factors for gastric cancer. Therefore, the accurate selection of individuals with AG and IM may be a key strategy for the prevention and/or early detection of gastric cancer. Although endoscopic evaluation using enhanced technologies such as narrow band imaging-magnification, the serum pepsinogen test, Helicobacter pylori serology, and trefoil factor 3 have been evaluated, a gold standard method to accurately select individuals with AG and IM has not emerged. In terms of managing patients at high risk of gastric cancer, it remains uncertain whether H. pylori eradication reverses and/or prevents the progression of AG and IM. Although endoscopic surveillance in high risk patients is expected to be beneficial, further prospective studies in large populations are needed to determine the optimal surveillance interval. PMID:25547086

  12. Diagnosis and management of high risk group for gastric cancer.

    PubMed

    Yoon, Hyuk; Kim, Nayoung

    2015-01-01

    Gastric cancer is associated with high morbidity and mortality worldwide. To reduce the socioeconomic burden related to gastric cancer, it is very important to identify and manage high risk group for gastric cancer. In this review, we describe the general risk factors for gastric cancer and define high risk group for gastric cancer. We discuss strategies for the effective management of patients for the prevention and early detection of gastric cancer. Atrophic gastritis (AG) and intestinal metaplasia (IM) are the most significant risk factors for gastric cancer. Therefore, the accurate selection of individuals with AG and IM may be a key strategy for the prevention and/or early detection of gastric cancer. Although endoscopic evaluation using enhanced technologies such as narrow band imaging-magnification, the serum pepsinogen test, Helicobacter pylori serology, and trefoil factor 3 have been evaluated, a gold standard method to accurately select individuals with AG and IM has not emerged. In terms of managing patients at high risk of gastric cancer, it remains uncertain whether H. pylori eradication reverses and/or prevents the progression of AG and IM. Although endoscopic surveillance in high risk patients is expected to be beneficial, further prospective studies in large populations are needed to determine the optimal surveillance interval.

  13. 64Cu DOTA-Trastuzumab PET/CT in Studying Patients With Gastric Cancer

    ClinicalTrials.gov

    2016-09-16

    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

  14. Minimally invasive surgery for gastric cancer.

    PubMed

    Güner, Ali; Hyung, Woo Jin

    2014-01-01

    The interest in minimally invasive surgery (MIS) has rapidly increased in recent decades and surgeons have adopted minimally invasive techniques due to its reduced invasiveness and numerous advantages for patients. With increased surgical experience and newly developed surgical instruments, MIS has become the preferred approach not only for benign disease but also for oncologic surgery. Recently, robotic systems have been developed to overcome difficulties of standard laparoscopic instruments during complex procedures. Its advantages including three-dimensional images, tremor filtering, motion scaling, articulated instruments, and stable retraction have created the opportunity to use robotic technology in many procedures including cancer surgery. Gastric cancer is one of the most common causes of cancer-related deaths worldwide. While its overall incidence has decreased worldwide, the proportion of early gastric cancer has increased mainly in eastern countries following mass screening programs. The shift in the paradigm of gastric cancer treatment is toward less invasive approaches in order to improve the patient's quality of life while adhering to oncological principles. In this review, we aimed to summarize the operative strategy and current literature in laparoscopic and robotic surgery for gastric cancer.

  15. Current issues and future perspectives of gastric cancer screening

    PubMed Central

    Hamashima, Chisato

    2014-01-01

    Gastric cancer remains the second leading cause of cancer death worldwide. About half of the incidence of gastric cancer is observed in East Asian countries, which show a higher mortality than other countries. The effectiveness of 3 new gastric cancer screening techniques, namely, upper gastrointestinal endoscopy, serological testing, and “screen and treat” method were extensively reviewed. Moreover, the phases of development for cancer screening were analyzed on the basis of the biomarker development road map. Several observational studies have reported the effectiveness of endoscopic screening in reducing mortality from gastric cancer. On the other hand, serologic testing has mainly been used for targeting the high-risk group for gastric cancer. To date, the effectiveness of new techniques for gastric cancer screening has remained limited. However, endoscopic screening is presently in the last trial phase of development before their introduction to population-based screening. To effectively introduce new techniques for gastric cancer screening in a community, incidence and mortality reduction from gastric cancer must be initially and thoroughly evaluated by conducting reliable studies. In addition to effectiveness evaluation, the balance of benefits and harms must be carefully assessed before introducing these new techniques for population-based screening. PMID:25320514

  16. Current issues and future perspectives of gastric cancer screening.

    PubMed

    Hamashima, Chisato

    2014-10-14

    Gastric cancer remains the second leading cause of cancer death worldwide. About half of the incidence of gastric cancer is observed in East Asian countries, which show a higher mortality than other countries. The effectiveness of 3 new gastric cancer screening techniques, namely, upper gastrointestinal endoscopy, serological testing, and "screen and treat" method were extensively reviewed. Moreover, the phases of development for cancer screening were analyzed on the basis of the biomarker development road map. Several observational studies have reported the effectiveness of endoscopic screening in reducing mortality from gastric cancer. On the other hand, serologic testing has mainly been used for targeting the high-risk group for gastric cancer. To date, the effectiveness of new techniques for gastric cancer screening has remained limited. However, endoscopic screening is presently in the last trial phase of development before their introduction to population-based screening. To effectively introduce new techniques for gastric cancer screening in a community, incidence and mortality reduction from gastric cancer must be initially and thoroughly evaluated by conducting reliable studies. In addition to effectiveness evaluation, the balance of benefits and harms must be carefully assessed before introducing these new techniques for population-based screening. PMID:25320514

  17. The future of gastric cancer prevention.

    PubMed

    Correa, Pelayo; Piazuelo, M Blanca; Camargo, M Constanza

    2004-01-01

    Despite advances in surgical treatment and chemotherapy, gastric cancer remains a major global health burden. The most recent estimates show that it is the fourth most common cancer and the second most common cause of cancer deaths worldwide. Various etiologic factors have been linked with the disease. It is widely accepted that Helicobacter pylori infection and high salt intake are positively associated with this neoplastic process. Controversial associations have been found with smoking or drinking habits. In contrast, there is convincing evidence that the adequate consumption of fresh fruits and vegetables reduces the risk of gastric cancer. Prevention intervention trials involving antioxidant supplements and anti- H. pylori treatment have shown beneficial effects in preventing the progression of pathologic changes in the gastric mucosa. On the other hand, recent advances related to differences in the genotypes of the bacteria and in human cytokine polymorphisms would allow the design and implementation of large-scale screening programs to identify subjects at the highest risk of gastric cancer. Curing the infection in such subjects and supplying adequate amounts of antioxidants should prevent a neoplastic outcome, and this intervention should be monitored by endoscopic surveillance. PMID:15052434

  18. Pembrolizumab, Combination Chemotherapy, and Radiation Therapy Before Surgery in Treating Adult Patients With Locally Advanced Gastroesophageal Junction or Gastric Cardia Cancer That Can Be Removed by Surgery

    ClinicalTrials.gov

    2016-06-27

    Adenocarcinoma of the Gastroesophageal Junction; Gastric Cardia Adenocarcinoma; Stage IB Gastric Cancer; Stage IIA Gastric Cancer; Stage IIB Gastric Cancer; Stage IIIA Gastric Cancer; Stage IIIB Gastric Cancer

  19. Recapitulating Human Gastric Cancer Pathogenesis: Experimental Models of Gastric Cancer.

    PubMed

    Ding, Lin; El Zaatari, Mohamad; Merchant, Juanita L

    2016-01-01

    This review focuses on the various experimental models to study gastric cancer pathogenesis, with the role of genetically engineered mouse models (GEMMs) used as the major examples. We review differences in human stomach anatomy compared to the stomachs of the experimental models, including the mouse and invertebrate models such as Drosophila and C. elegans. The contribution of major signaling pathways, e.g., Notch, Hedgehog, AKT/PI3K is discussed in the context of their potential contribution to foregut tumorigenesis. We critically examine the rationale behind specific GEMMs, chemical carcinogens, dietary promoters, Helicobacter infection, and direct mutagenesis of relevant oncogenes and tumor suppressor that have been developed to study gastric cancer pathogenesis. Despite species differences, more efficient and effective models to test specific genes and pathways disrupted in human gastric carcinogenesis have yet to emerge. As we better understand these species differences, "humanized" versions of mouse models will more closely approximate human gastric cancer pathogenesis. Towards that end, epigenetic marks on chromatin, the gut microbiota, and ways of manipulating the immune system will likely move center stage, permitting greater overlap between rodent and human cancer phenotypes thus providing a unified progression model. PMID:27573785

  20. Advances in gastric cancer prevention.

    PubMed

    Giordano, Antonio; Cito, Letizia

    2012-09-10

    Gastric cancer is a multifactorial neoplastic pathology numbering among its causes both environmental and genetic predisposing factors. It is mainly diffused in South America and South-East Asia, where it shows the highest morbility percentages and it is relatively scarcely diffused in Western countries and North America. Although molecular mechanisms leading to gastric cancer development are only partially known, three main causes are well characterized: Helicobacter pylori (H. pylori) infection, diet rich in salted and/or smoked food and red meat, and epithelial cadherin (E-cadherin) mutations. Unhealthy diet and H. pylori infection are able to induce in stomach cancer cells genotypic and phenotypic transformation, but their effects may be crossed by a diet rich in vegetables and fresh fruits. Various authors have recently focused their attention on the importance of a well balanced diet, suggesting a necessary dietary education starting from childhood. A constant surveillance will be necessary in people carrying E-cadherin mutations, since they are highly prone in developing gastric cancer, also within the inner stomach layers. Above all in the United States, several carriers decided to undergo a gastrectomy, preferring changing their lifestyle than living with the awareness of the development of a possible gastric cancer. This kind of choice is strictly personal, hence a decision cannot be suggested within the clinical management. Here we summarize the key points of gastric cancer prevention analyzing possible strategies referred to the different predisposing factors. We will discuss about the effects of diet, H. pylori infection and E-cadherin mutations and how each of them can be handled. PMID:23061031

  1. Functional role of autophagy in gastric cancer

    PubMed Central

    2016-01-01

    Autophagy is a highly regulated catabolic pathway responsible for the degradation of long-lived proteins and damaged intracellular organelles. Perturbations in autophagy are found in gastric cancer. In host gastric cells, autophagy can be induced by Helicobacter pylori (or H. pylori) infection, which is associated with the oncogenesis of gastric cancer. In gastric cancer cells, autophagy has both pro-survival and pro-death functions in determining cell fate. Besides, autophagy modulates gastric cancer metastasis by affecting a wide range of pathological events, including extracellular matrix (ECM) degradation, epithelial-to-mesenchymal transition (EMT), tumor angiogenesis, and tumor microenvironment. In addition, some of the autophagy-related proteins, such as Beclin 1, microtubule-associated protein 1 light chain 3 (MAP1-LC3), and p62/sequestosome 1 (SQSTM1) have certain prognostic values for gastric cancer. In this article, we review the recent studies regarding the functional role of autophagy in gastric cancer. PMID:26910278

  2. Overexpression of neuritin in gastric cancer

    PubMed Central

    YUAN, MING; LI, YONGJUN; ZHONG, CHEN; LI, YONGKANG; NIU, JIANHUA; GONG, JIANPING

    2015-01-01

    The aim of the present study was to investigate the expression of neuritin in gastric cancer tissues, in order to explore the association between the expression of neuritin and the occurrence and development of gastric cancer. Tissue specimens were collected from 58 patients with gastric cancer. Immunohistochemistry, western blot analysis and reverse transcription-polymerase chain reaction (RT-PCR) were used to determine the expression of neuritin in the gastric cancer and corresponding adjacent normal gastric tissues. The expression rate of neuritin in gastric cancer tissues was 96.55% (56/58), demonstrating no statistically significant difference from the expression rate in the adjacent normal tissues (94.83%) (P>0.05). However, the rate of strong neuritin expression in gastric cancer tissues (82.76%) was significantly increased compared with the rate in the adjacent normal tissues (15.52%) (P<0.05). Neuritin expression exhibited no correlation with the gender or age of patients, tumor-node-metastasis staging, tumor depth, presence of lymph node metastasis, histological or pathological type of the tumor or presence of distant metastasis (P>0.05). As determined by RT-PCR and western blot analysis, the mRNA expression of neuritin in gastric cancer tissues was markedly increased compared with the expression in the adjacent normal tissues. In conclusion, neuritin is highly expressed in gastric cancer tissues, suggesting that neuritin may act as a novel potential target for the treatment of gastric cancer. PMID:26788217

  3. Non-coding RNAs and gastric cancer.

    PubMed

    Li, Pei-Fei; Chen, Sheng-Can; Xia, Tian; Jiang, Xiao-Ming; Shao, Yong-Fu; Xiao, Bing-Xiu; Guo, Jun-Ming

    2014-05-14

    Non-coding RNAs (ncRNAs) play key roles in development, proliferation, differentiation and apoptosis. Altered ncRNA expression is associated with gastric cancer occurrence, invasion, and metastasis. Moreover, aberrant expression of microRNAs (miRNAs) is significantly related to gastric cancer tumor stage, size, differentiation and metastasis. MiRNAs interrupt cellular signaling pathways, inhibit the activity of tumor suppressor genes, and affect the cell cycle in gastric cancer cells. Some miRNAs, including miR-21, miR-106a and miR-421, could be potential markers for the diagnosis of gastric cancer. Long non-coding RNAs (lncRNAs), a new research hotspot among cancer-associated ncRNAs, play important roles in epigenetic, transcriptional and post-transcriptional regulation. Several gastric cancer-associated lncRNAs, such as CCAT1, GACAT1, H19, and SUMO1P3, have been explored. In addition, Piwi-interacting RNAs, another type of small ncRNA that is recognized by gastroenterologists, are involved in gastric carcinogenesis, and piR-651/823 represents an efficient diagnostic biomarker of gastric cancer that can be detected in the blood and gastric juice. Small interfering RNAs also function in post-transcriptional regulation in gastric cancer and might be useful in gastric cancer treatment. PMID:24833871

  4. The journey of personalizing gastric cancer treatment.

    PubMed

    Yan, Li

    2016-01-01

    Gastric cancer ranks the fourth most prevalent malignancy yet it is the second leading cause of cancer-related death. Every year, gastric cancer adds nearly 1 million new cancer cases, and 723,000 or 10% of cancer deaths to the global cancer burden. Approximately, 405,000 or 43% of the new cases and 325,000 or 45% of the deaths are in China, making gastric cancer a particularly challenging malignancy. This thematic series discusses the molecular classifications of gastric cancer by the Cancer Genome Atlas (TCGA) and the Asian Cancer Research Group (ACRG) as well as the implications in personalized therapeutic choices; discusses the evolution of gastric surgery and presents perspectives on surgical techniques in treating gastric cancer; and reviews current and emerging targeted agents as well as immunotherapies in treating gastric cancer. With these advancements in molecular characterization, surgical intervention, and targeted and immunotherapies, gastric cancer will enter a personalized medicine era in the next 5 years. PMID:27581614

  5. Drugs Approved for Stomach (Gastric) Cancer

    Cancer.gov

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for stomach (gastric) cancer. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries.

  6. Cate's Story: Hereditary Diffuse Gastric Cancer.

    PubMed

    Rogers, Megan

    2016-08-01

    Gastric cancer is a major cause of cancer-related mortality worldwide and is thought to be responsible for about 10% of cancer-related deaths across the globe. A small proportion of all gastric cancers arise because of a known hereditary syndrome, the most common of which is hereditary diffuse gastric cancer (HDGC). This is an autosomal dominant genetic disease characterized by an increased risk of developing diffuse gastric cancer at a young age. The gene responsible for HDGC is CDH1, also known as E-cadherin, a germline mutation conferring an 80% risk of developing gastric cancer during the lifetime of the carrier. Females with germline CDH1 mutations face an additional risk of developing lobular breast cancer, with a reported cumulative risk of 60% by the age of 80 years.
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  7. Pathogenesis and risk factors for gastric cancer after Helicobacter pylori eradication

    PubMed Central

    Ohba, Reina; Iijima, Katsunori

    2016-01-01

    Helicobacter pylori (H. pylori) infection was thought to be the main cause of gastric cancer, and its eradication showed improvement in gastric inflammation and decreased the risk of gastric cancer. Recently, a number of studies reported the occurrence of gastric cancer after successful eradication. Patients infected with H. pylori, even after eradication, have a higher risk for the occurrence of gastric cancer when compared with uninfected patients. Metachronous gastric cancer occurs frequently following the endoscopic removal of early gastric cancer. These data indicate that metachronous cancer leads to the occurrence of gastric cancer even after successful eradication of H. pylori. The pathogenesis of this metachronous cancer remains unclear. Further research is needed to identify biomarkers to predict the development of metachronous gastric cancer and methods for gastric cancer screening. In this article, we review the role of the H. pylori in carcinogenesis and the histological and endoscopic characteristics and risk factors for metachronous gastric cancer after eradication. Additionally, we discuss recent risk predictions and possible approaches for reducing the risk of metachronous gastric cancer after eradication. PMID:27672424

  8. Pathogenesis and risk factors for gastric cancer after Helicobacter pylori eradication.

    PubMed

    Ohba, Reina; Iijima, Katsunori

    2016-09-15

    Helicobacter pylori (H. pylori) infection was thought to be the main cause of gastric cancer, and its eradication showed improvement in gastric inflammation and decreased the risk of gastric cancer. Recently, a number of studies reported the occurrence of gastric cancer after successful eradication. Patients infected with H. pylori, even after eradication, have a higher risk for the occurrence of gastric cancer when compared with uninfected patients. Metachronous gastric cancer occurs frequently following the endoscopic removal of early gastric cancer. These data indicate that metachronous cancer leads to the occurrence of gastric cancer even after successful eradication of H. pylori. The pathogenesis of this metachronous cancer remains unclear. Further research is needed to identify biomarkers to predict the development of metachronous gastric cancer and methods for gastric cancer screening. In this article, we review the role of the H. pylori in carcinogenesis and the histological and endoscopic characteristics and risk factors for metachronous gastric cancer after eradication. Additionally, we discuss recent risk predictions and possible approaches for reducing the risk of metachronous gastric cancer after eradication. PMID:27672424

  9. Pathogenesis and risk factors for gastric cancer after Helicobacter pylori eradication.

    PubMed

    Ohba, Reina; Iijima, Katsunori

    2016-09-15

    Helicobacter pylori (H. pylori) infection was thought to be the main cause of gastric cancer, and its eradication showed improvement in gastric inflammation and decreased the risk of gastric cancer. Recently, a number of studies reported the occurrence of gastric cancer after successful eradication. Patients infected with H. pylori, even after eradication, have a higher risk for the occurrence of gastric cancer when compared with uninfected patients. Metachronous gastric cancer occurs frequently following the endoscopic removal of early gastric cancer. These data indicate that metachronous cancer leads to the occurrence of gastric cancer even after successful eradication of H. pylori. The pathogenesis of this metachronous cancer remains unclear. Further research is needed to identify biomarkers to predict the development of metachronous gastric cancer and methods for gastric cancer screening. In this article, we review the role of the H. pylori in carcinogenesis and the histological and endoscopic characteristics and risk factors for metachronous gastric cancer after eradication. Additionally, we discuss recent risk predictions and possible approaches for reducing the risk of metachronous gastric cancer after eradication.

  10. Pathogenesis and risk factors for gastric cancer after Helicobacter pylori eradication

    PubMed Central

    Ohba, Reina; Iijima, Katsunori

    2016-01-01

    Helicobacter pylori (H. pylori) infection was thought to be the main cause of gastric cancer, and its eradication showed improvement in gastric inflammation and decreased the risk of gastric cancer. Recently, a number of studies reported the occurrence of gastric cancer after successful eradication. Patients infected with H. pylori, even after eradication, have a higher risk for the occurrence of gastric cancer when compared with uninfected patients. Metachronous gastric cancer occurs frequently following the endoscopic removal of early gastric cancer. These data indicate that metachronous cancer leads to the occurrence of gastric cancer even after successful eradication of H. pylori. The pathogenesis of this metachronous cancer remains unclear. Further research is needed to identify biomarkers to predict the development of metachronous gastric cancer and methods for gastric cancer screening. In this article, we review the role of the H. pylori in carcinogenesis and the histological and endoscopic characteristics and risk factors for metachronous gastric cancer after eradication. Additionally, we discuss recent risk predictions and possible approaches for reducing the risk of metachronous gastric cancer after eradication.

  11. Stomach (Gastric) Cancer Prevention

    MedlinePlus

    ... of stomach cancer. Some studies show that eating fruits and vegetables that are high in vitamin C and beta carotene may lower the risk ... take can prevent cancer. These may include eating fruits and vegetables, exercising, ... vitamins, minerals, or food supplements. New ways to prevent ...

  12. Current Perspectives on Gastric Cancer.

    PubMed

    Marqués-Lespier, Juan M; González-Pons, María; Cruz-Correa, Marcia

    2016-09-01

    Gastric cancer (GC) is third leading cause of cancer-related death. Only 28.3% of new GC cases survive more than 5 years. Although incidence has declined in the United States, an increase is estimated for 2016. Risk factors include sex (risk is higher in men), Helicobacter pylori infection, heredity, and lifestyle. GC is usually diagnosed between the ages of 60-80 years. Prognosis of GC is largely dependent on the tumor stage at diagnosis and classification as intestinal or diffuse type; diffuse-type GC has worse prognosis. Chemoprevention has been shown to decrease risk, but is currently not used clinically. PMID:27546840

  13. Ramucirumab: successfully targeting angiogenesis in gastric cancer.

    PubMed

    Javle, Milind; Smyth, Elizabeth C; Chau, Ian

    2014-12-01

    Gastric cancer is the fourth most common cancer globally and represents the second most common cause of cancer-related mortality. Early detection, aggressive surgical resection, and postoperative adjuvant therapy have led to survival improvement for early-stage gastric cancer, particularly in Asian countries. Unfortunately, advanced gastric cancer continues to pose a formidable challenge with few gains being reported recently. Trastuzumab was the first targeted agent to be approved for the treatment of advanced gastric cancer in 2010. The failure of the AVAGAST trial was a setback for antiangiogenic therapy for this disease. Ramucirumab is a monoclonal antibody that binds to VEGF-R2 and prevents its activation. The recent REGARD trial was a randomized phase III trial of ramucirumab vs. placebo for patients with advanced, pretreated gastric cancer that met its primary endpoint of increased overall survival. The toxicity of ramucirumab was modest in this setting, with an increased risk of grade 3 or higher hypertension (8% vs. 3%, with ramucirumab and placebo, respectively). The subsequent RAINBOW trial of paclitaxel plus ramucirumab vs. paclitaxel plus placebo for advanced pretreated gastric cancer confirmed the survival advantage of this antiangiogenic agent in gastric cancer. Ramucirumab is the first FDA-approved therapy for advanced gastric cancer after prior chemotherapy.

  14. Gastric cancer: new genetic developments.

    PubMed

    Lynch, Henry T; Grady, William; Suriano, Gianpaolo; Huntsman, David

    2005-06-01

    Gastric cancer's (GC) incidence shows large geographic differences worldwide with the lowest rates occurring in most Western industrialized countries including the United States and the United Kingdom; in contrast, relatively high rates of GC occur in Japan, Korea, China, and South America, particularly Chile. The Laurén classification system classifies GC under two major histopathological variants: 1) an intestinal type and 2) a diffuse type. The intestinal type is more common in the general population, more likely to be sporadic and related to environmental factors such as diet, particularly salted fish and meat as well as smoked foods, cigarette smoking, and alcohol use. It exhibits components of glandular, solid, or intestinal architecture, as well as tubular structures. On the other hand, the diffuse type is more likely to have a primary genetic etiology, a subset of which, known as hereditary diffuse gastric cancer (HDGC), is due to the E-cadherin (CDH1) germline mutation. The diffuse type pathology is characterized by poorly cohesive clusters of cells which infiltrate the gastric wall, leading to its widespread thickening and rigidity of the gastric wall, known as linitis plastica. Helicobacter pylori infection is associated with risk for both the intestinal and diffuse varieties of gastric cancer. Germline truncating mutations of the CDH1 gene, which codes for the E-cadherin protein, were initially identified in three Maori families from New Zealand that were predisposed to diffuse GC. Since then, similar mutations have been described in more than 40 additional HDGC families of diverse ethnic backgrounds. It is noteworthy that two-thirds of HDGC families reported to date have proved negative for the CDH1 germline mutation. A number of candidate genes have been identified through analysis of the molecular biology of E-cadherin. Patients with evidence of the CDH1 germline mutation in the context of a family history of HDGC must be considered as candidates

  15. What gastric cancer proteomic studies show about gastric carcinogenesis?

    PubMed

    Leal, Mariana Ferreira; Wisnieski, Fernanda; de Oliveira Gigek, Carolina; do Santos, Leonardo Caires; Calcagno, Danielle Queiroz; Burbano, Rommel Rodriguez; Smith, Marilia Cardoso

    2016-08-01

    Gastric cancer is a complex, heterogeneous, and multistep disease. Over the past decades, several studies have aimed to determine the molecular factors that lead to gastric cancer development and progression. After completing the human genome sequencing, proteomic technologies have presented rapid progress. Differently from the relative static state of genome, the cell proteome is dynamic and changes in pathologic conditions. Proteomic approaches have been used to determine proteome profiles and identify differentially expressed proteins between groups of samples, such as neoplastic and nonneoplastic samples or between samples of different cancer subtypes or stages. Therefore, proteomic technologies are a useful tool toward improving the knowledge of gastric cancer molecular pathogenesis and the understanding of tumor heterogeneity. This review aimed to summarize the proteins or protein families that are frequently identified by using high-throughput screening methods and which thus may have a key role in gastric carcinogenesis. The increased knowledge of gastric carcinogenesis will clearly help in the development of new anticancer treatments. Although the studies are still in their infancy, the reviewed proteins may be useful for gastric cancer diagnosis, prognosis, and patient management. PMID:27126070

  16. What gastric cancer proteomic studies show about gastric carcinogenesis?

    PubMed

    Leal, Mariana Ferreira; Wisnieski, Fernanda; de Oliveira Gigek, Carolina; do Santos, Leonardo Caires; Calcagno, Danielle Queiroz; Burbano, Rommel Rodriguez; Smith, Marilia Cardoso

    2016-08-01

    Gastric cancer is a complex, heterogeneous, and multistep disease. Over the past decades, several studies have aimed to determine the molecular factors that lead to gastric cancer development and progression. After completing the human genome sequencing, proteomic technologies have presented rapid progress. Differently from the relative static state of genome, the cell proteome is dynamic and changes in pathologic conditions. Proteomic approaches have been used to determine proteome profiles and identify differentially expressed proteins between groups of samples, such as neoplastic and nonneoplastic samples or between samples of different cancer subtypes or stages. Therefore, proteomic technologies are a useful tool toward improving the knowledge of gastric cancer molecular pathogenesis and the understanding of tumor heterogeneity. This review aimed to summarize the proteins or protein families that are frequently identified by using high-throughput screening methods and which thus may have a key role in gastric carcinogenesis. The increased knowledge of gastric carcinogenesis will clearly help in the development of new anticancer treatments. Although the studies are still in their infancy, the reviewed proteins may be useful for gastric cancer diagnosis, prognosis, and patient management.

  17. [Early gastric cancer--two case reports].

    PubMed

    Neziha, Belkahla; Houneida, Bouzi; Mohamed, Jouini; Hajer, Ouerghi; Nadia, Maamouri; Imed, Cheikh; Faouzi, Chebbi; Saadia, Bouraoui; Nidhameddine, Kchir; Ahmed, Ben Ammar

    2005-11-01

    Gastric cancer is a serious disease with a high mortality rate. Early diagnosis of the disease improves its prognosis. We report two cases of early gastric cancer and we specify the clinical, endoscopic, histologic and therapeutic aspects of the disease. This study is about two female patients, respectively, 36 and 70 years old. The diagnosis of early gastric cancer was based on pathologic examination of the resected stomach. The two patients are in remission 2 years and 6 months later, respectively. The diagnosis of early gastric cancer is often made on nonspecific symptoms. Oeso-gastro-duodenoscopy shows gastric mucosal anomalies. Pathologic examination of gastric biopsies confirm the diagnosis of adenocarcinoma. Endoscopic ultrasound is essential; it specifies the submucosal infiltration and evaluates the lymph node invasion. Surgery is the primary treatment but in some cases endoscopic mucosal resection provides good long-term results. Early diagnosis of adenocarcinoma improves the prognosis of the disease, which remains poor nowadays.

  18. Helicobacter pylori Diversity and Gastric Cancer Risk

    PubMed Central

    2016-01-01

    ABSTRACT Gastric cancer is a leading cause of cancer-related death worldwide. Helicobacter pylori infection is the strongest known risk factor for this malignancy. An important goal is to identify H. pylori-infected persons at high risk for gastric cancer, so that these individuals can be targeted for therapeutic intervention. H. pylori exhibits a high level of intraspecies genetic diversity, and over the past two decades, many studies have endeavored to identify strain-specific features of H. pylori that are linked to development of gastric cancer. One of the most prominent differences among H. pylori strains is the presence or absence of a 40-kb chromosomal region known as the cag pathogenicity island (PAI). Current evidence suggests that the risk of gastric cancer is very low among persons harboring H. pylori strains that lack the cag PAI. Among persons harboring strains that contain the cag PAI, the risk of gastric cancer is shaped by a complex interplay among multiple strain-specific bacterial factors as well as host factors. This review discusses the strain-specific properties of H. pylori that correlate with increased gastric cancer risk, focusing in particular on secreted proteins and surface-exposed proteins, and describes evidence from cell culture and animal models linking these factors to gastric cancer pathogenesis. Strain-specific features of H. pylori that may account for geographic variation in gastric cancer incidence are also discussed. PMID:26814181

  19. Eradication of gastric cancer and more efficient gastric cancer surveillance in Japan: two peas in a pod.

    PubMed

    Graham, David Y; Asaka, Masahiro

    2010-01-01

    We provide a historical review and update on current thinking regarding the possibility of elimination of gastric cancer from Japan. Because Helicobacter pylori infection is the cause gastric cancer, its elimination forms the cornerstone of eradication of gastric cancer. However, simply eradicating H. pylori from the entire population will not immediately solve the problem because many patients with H. pylori infections have already developed the precursor lesion, atrophic gastritis. Cure of H. pylori in these high risk patients will only reduce the risk of subsequent cancer. In contrast, treatment of low risk patients will prevent cancer. Thus, to eliminate gastric cancer it is necessary to identify and treat all infected individuals. In addition, those at increased risk for gastric cancer (i.e., atrophic gastritis irrespective of age) should be considered for endoscopic surveillance to identify those cancers that develop at an early stage. We propose that severity and extent of atrophy be used to separate those expected to benefit from endoscopy and annual surveillance from those with little or no potential benefit. We suggest an algorithm for eradicating gastric cancer that incorporates H. pylori and atrophic gastritis testing, H. pylori therapy, and surveillance to institute a program of surveillance restricted to those who could benefit most (i.e., those with moderate or severe atrophy). This will also allow a much closer matching of surveillance capacity and surveillance need making surveillance more clinically- and cost-effective.

  20. Gastric cancer detection in gastric ulcer disease.

    PubMed Central

    Mountford, R A; Brown, P; Salmon, P R; Alvarenga, C; Neumann, C S; Read, A E

    1980-01-01

    A retrospective study has been performed of all cases of gastric ulcer diagnosed or investigated within the Endoscopy Unit of the Department of Medicine, Bristol, over a three year period (1974-76). The average length of follow-up was two years. Two hundred and sixty five cases of gastric ulcer were studied of which 37 proved to be malignant (14%). Presenting complaints of anorexia, weight loss, nausea and/or vomiting, and multiple (greater than 3) symptoms, were commoner in the malignant ulcer group. Ulcer site and the presence of coexisting duodenal ulceration were largely unhelpful in deciding the status of an ulcer. Malignant ulcers tended to be large (greater than 1 cm diameter). Radiology was highly unreliable in distinguishing benign from malignant ulcers. Visual inspection at endoscopy was more reliable, but associated with a tendency to over-diagnose malignancy. False positive biopsies were uncommon (two cases). Three cases of clinically unsuspected superficial gastric carcinoma were revealed. Repeated endoscopy and biopsy of all gastric ulcers until they are completely healed is advised. Images Fig. 5 Fig. 6 PMID:7364322

  1. Molecular targeted therapy for the treatment of gastric cancer.

    PubMed

    Xu, Wenting; Yang, Zhen; Lu, Nonghua

    2016-01-04

    Despite the global decline in the incidence and mortality of gastric cancer, it remains one of the most common malignant tumors of the digestive system. Although surgical resection is the preferred treatment for gastric cancer, chemotherapy is the preferred treatment for recurrent and advanced gastric cancer patients who are not candidates for reoperation. The short overall survival and lack of a standard chemotherapy regimen make it important to identify novel treatment modalities for gastric cancer. Within the field of tumor biology, molecular targeted therapy has attracted substantial attention to improve the specificity of anti-cancer efficacy and significantly reduce non-selective resistance and toxicity. Multiple clinical studies have confirmed that molecular targeted therapy acts on various mechanisms of gastric cancer, such as the regulation of epidermal growth factor, angiogenesis, immuno-checkpoint blockade, the cell cycle, cell apoptosis, key enzymes, c-Met, mTOR signaling and insulin-like growth factor receptors, to exert a stronger anti-tumor effect. An in-depth understanding of the mechanisms that underlie molecular targeted therapies will provide new insights into gastric cancer treatment.

  2. Active Targeted Nanoparticles for Oral Administration of Gastric Cancer Therapy.

    PubMed

    Lin, Yu-Hsin; Chen, Zih-Rou; Lai, Chih-Ho; Hsieh, Chia-Hung; Feng, Chun-Lung

    2015-09-14

    Gastric carcinogenesis is a commonly diagnosed type of cancer and has a dismal prognosis because of the rate at which it aggressively spreads and because of the lack of effective therapies to stop its progression. This study evaluated a type of oral drug delivery system of a potential target-activated nanosizer comprising a fucose-conjugated chitosan and polyethylene glycol-conjugated chitosan complex with gelatin containing encapsulated green tea polyphenol extract epigallocatechin-3-gallate, allowing oral administration of the drug through a site-specific release in gastric cancer cells. The results demonstrated that the nanoparticles effectively reduced drug release within gastric acids and that a controlled epigallocatechin-3-gallate release inhibited gastric cancer cell growth, induced cell apoptosis, and reduced vascular endothelial growth factor protein expression. Furthermore, in vivo assay results indicated that the prepared epigallocatechin-3-gallate-loaded fucose-chitosan/polyethylene glycol-chitosan/gelatin nanoparticles significantly affected gastric tumor activity and reduced gastric and liver tissue inflammatory reaction in an orthotopic gastric tumor mouse model.

  3. Isoprenaline Induces Periostin Expression in Gastric Cancer

    PubMed Central

    Liu, Guo-Xiao; Xi, Hong-Qing; Sun, Xiao-Yan; Geng, Zhi-Jun; Yang, Shao-Wei; Lu, Yan-Jie

    2016-01-01

    Purpose Periostin mediates critical steps in gastric cancer and is involved in various signaling pathways. However, the roles of periostin in promoting gastric cancer metastasis are not clear. The aim of this study was to investigate the relevance between periostin expression and gastric cancer progression and the role of stress-related hormones in the regulation of cancer development and progression. Materials and Methods Normal, cancerous and metastatic gastric tissues were collected from patients diagnosed with advanced gastric cancer. The in vivo expression of periostin was evaluated by in situ hybridization and immunofluorescent staining. Meanwhile, human gastric adenocarcinoma cell lines MKN-45 and BGC-803 were used to detect the in vitro expression of periostin by using quantitative real-time polymerase chain reaction (PCR) and western blotting. Results Periostin is expressed in the stroma of the primary gastric tumors and metastases, but not in normal gastric tissue. In addition, we observed that periostin is located mainly in pericryptal fibroblasts, but not in the tumor cells, and strongly correlated to the expression of α-smooth muscle actin (SMA). Furthermore, the distribution patterns of periostin were broader as the clinical staging of tumors progressed. We also identified a role of stress-related signaling in promoting cancer development and progression, and found that isoprenaline upregulated expression levels of periostin in gastric cancer cells. Conclusion These findings suggest that the distribution pattern of periostin was broader as the clinical staging of the tumor progressed and found that isoprenaline upregulated expression levels of periostin in gastric cancer cells. PMID:26996552

  4. Emerging role of S-1 in gastric cancer.

    PubMed

    Krasniqi, Eriseld; Pellicori, Stefania; Formica, Vincenzo

    2015-01-01

    Gastric cancer remains one of the most important malignancies worldwide in terms of incidence and mortality. The treatment is based on the combination of local surgery and radiation therapy as well as systemic chemotherapy and targeted molecules. Fluoropyrimidines and particularly 5-fluorouracil (FU) represent still the backbone for gastric cancer chemotherapy and new molecular versions of this molecule have been brought to clinical practice in order to improve benefits and reduce adverse effects. S-1 is an oral prodrug of 5-FU, which has demonstrated high effectiveness for gastric cancer treatment and a favorable safety profile. Currently, there are geographic differences in the treatment of gastric cancer and in the use of S-1, which is a mainstay of gastric cancer management in Eastern countries, but is not part of the standard care in the rest of the world. In this review, we gathered data from phase I, II, and III trials of S-1 in gastric cancer, in order to define its real benefit-risk ratio and assess whether geographic differences in S-1 use are justified by unchangeable factors.

  5. Gastric Cancer: New Drugs – New Strategies

    PubMed Central

    Schulte, Nadine; Ebert, Matthias P.; Härtel, Nicolai

    2014-01-01

    Background Gastric cancer is the second most common cause of cancer-related deaths worldwide. There are large geographic variations in the incidence of these tumors, with 60% occurring in East Asia. For patients with resectable disease, surgery and perioperative treatment can be effective. For patients with advanced gastric cancer, chemotherapy regimens result in a median survival of 9-11 months. In general, the prognosis for advanced disease is poor and 5-year overall survival rates are around 15%. Combination therapies yield better survival rates, albeit with increased toxicity. Therefore, more effective and less toxic treatment regimens are needed. Summary The molecular aberrations that characterize the different subgroups of gastric cancer have been used as therapeutic targets. However, the heterogeneity and complexity of gastric cancers is a major challenge for the development of effective targeted therapies. This review examines the main molecular targets in the treatment of gastric cancer, namely the vascular endothelial growth factor (VEGF), human epidermal growth factor receptor 2 (HER2), hepatocyte growth factor (HGF)/c-Met, epidermal growth factor receptor (EGFR) and phosphoinositide 3-kinase (PI3K)/Akt pathways. Key Message The molecular aberrations characteristic of gastric cancer are being explored for the development of targeted therapies, including the VEGF, HER2, HGF/c-Met, EGFR and PI3K/Akt signaling pathways. Practical Implications Trastuzumab, an antibody which targets HER2, is the first approved targeted therapy for the treatment of gastric cancer. However, trastuzumab is only effective in HER2-positive tumors (about 10-20% of all gastric cancers). Ramucirumab, which targets the VEGF receptor 2, has yielded benefits with respect to overall survival in a phase III trial and is an effective treatment for advanced gastric cancer with approval in second-line treatment. Apatinib and rilotumumab are another two promising new agents currently under

  6. Worldwide practice in gastric cancer surgery

    PubMed Central

    Brenkman, Hylke JF; Haverkamp, Leonie; Ruurda, Jelle P; van Hillegersberg, Richard

    2016-01-01

    AIM: To evaluate the current status of gastric cancer surgery worldwide. METHODS: An international cross-sectional survey on gastric cancer surgery was performed amongst international upper gastro-intestinal surgeons. All surgical members of the International Gastric Cancer Association were invited by e-mail to participate. An English web-based survey had to be filled in with regard to their surgical preferences. Questions asked included hospital volume, the use of neoadjuvant treatment, preferred surgical approach, extent of the lymphadenectomy and preferred anastomotic technique. The invitations were sent in September 2013 and the survey was closed in January 2014. RESULTS: The corresponding specific response rate was 227/615 (37%). The majority of respondents: originated from Asia (54%), performed > 21 gastrectomies per year (79%) and used neoadjuvant chemotherapy (73%). An open surgical procedure was performed by the majority of surgeons for distal gastrectomy for advanced cancer (91%) and total gastrectomy for both early and advanced cancer (52% and 94%). A minimally invasive procedure was preferred for distal gastrectomy for early cancer (65%). In Asia surgeons preferred a minimally invasive procedure for total gastrectomy for early cancer also (63%). A D1+ lymphadenectomy was preferred in early gastric cancer (52% for distal, 54% for total gastrectomy) and a D2 lymphadenectomy was preferred in advanced gastric cancer (93% for distal, 92% for total gastrectomy) CONCLUSION: Surgical preferences for gastric cancer surgery vary between surgeons worldwide. Although the majority of surgeons use neoadjuvant chemotherapy, minimally invasive techniques are still not widely adapted. PMID:27099448

  7. Helicobacter pylori Update: Gastric Cancer, Reliable Therapy, and Possible Benefits

    PubMed Central

    Graham, David Y.

    2015-01-01

    Helicobacter pylori infection contributes to development of diverse gastric and extra-gastric diseases. The infection is necessary but not sufficient for development of gastric adenocarcinoma. Its eradication would eliminate a major worldwide cause of cancer death, so there is much interest in identifying how, if, and when this can be accomplished. There are several mechanisms by which H pylori contributes to development of gastric cancer. Gastric adenocarcinoma is one of many cancers associated with inflammation, which is induced by H pylori infection, yet the bacteria also cause genetic and epigenetic changes that lead to genetic instability in gastric epithelial cells. H pylori eradication reduces both. However, many factors must be considered in determining whether treating this bacterial infection will prevent cancer or only reduce its risk—these must be considered in designing reliable and effective eradication therapies. Furthermore, H pylori infection has been proposed to provide some benefits, such as reducing the risks of obesity or childhood asthma, although there are no convincing data to support the benefits of H pylori infections. PMID:25655557

  8. Targeting receptor tyrosine kinases in gastric cancer

    PubMed Central

    Morishita, Asahiro; Gong, Jian; Masaki, Tsutomu

    2014-01-01

    Molecularly targeted therapeutic agents are constantly being developed and have been shown to be effective in various clinical trials. One group of representative targeted oncogenic kinases, the receptor tyrosine kinases (RTKs), has been associated with gastric cancer development. Trastuzumab, an inhibitor of ERBB2, has been approved for the treatment of gastric cancer, although other receptor tyrosine kinases, such as epidermal growth factor receptor, vascular endothelial growth factor, platelet-derived growth factor receptor, c-Met, IGF-1R and fibroblast growth factor receptor 2, are also activated in gastric cancer. The promising results of the trastuzumab clinical trial for gastric cancer resulted in the approval of trastuzumab-based therapy as a first-line treatment for human epidermal growth factor receptor 2-positive patients. On the other hand, the trial examining bevacizumab in combination with conventional chemotherapy did not meet its primary goal of increasing the overall survival time of gastric cancer patients; however, a significantly higher response rate and a longer progression-free survival were observed in the bevacizumab arm of the trial. Other clinical trials, especially phase III trials that have tested drugs targeting RTKs, such as cetuximab, panitumumab, gefitinib, erlotinib, figitumumab, sorafenib, sunitinib and lapatinib, have shown that these drugs have modest effects against gastric cancer. This review summarizes the recent results from the clinical trials of molecularly targeted drugs and suggests that further improvements in the treatment of advanced gastric cancer can be achieved through the combination of conventional drugs with the new molecularly targeted therapies. PMID:24782606

  9. Hedgehog Signaling Regulates the Survival of Gastric Cancer Cells by Regulating the Expression of Bcl-2

    PubMed Central

    Han, Myoung-Eun; Lee, Young-Suk; Baek, Sun-Yong; Kim, Bong-Seon; Kim, Jae-Bong; Oh, Sae-Ock

    2009-01-01

    Gastric cancer is the second most common cause of cancer deaths worldwide. The underlying molecular mechanisms of its carcinogenesis are relatively poorly characterized. Hedgehog (Hh) signaling, which is critical for development of various organs including the gastrointestinal tract, has been associated with gastric cancer. The present study was undertaken to reveal the underlying mechanism by which Hh signaling controls gastric cancer cell proliferation. Treatment of gastric cancer cells with cyclopamine, a specific inhibitor of Hh signaling pathway, reduced proliferation and induced apoptosis of gastric cancer cells. Cyclopamine treatment induced cytochrome c release from mitochondria and cleavage of caspase 9. Moreover, Bcl-2 expression was significantly reduced by cyclopamine treatment. These results suggest that Hh signaling regulates the survival of gastric cancer cells by regulating the expression of Bcl-2. PMID:19742123

  10. Argininosuccinate synthetase 1 suppression and arginine restriction inhibit cell migration in gastric cancer cell lines.

    PubMed

    Shan, Yan-Shen; Hsu, Hui-Ping; Lai, Ming-Derg; Yen, Meng-Chi; Chen, Wei-Ching; Fang, Jung-Hua; Weng, Tzu-Yang; Chen, Yi-Ling

    2015-01-01

    Gastric cancer metastasis remains a major cause of cancer-related deaths. There is an urgent need to develop new therapeutic approaches targeting metastatic gastric cancer. Argininosuccinate synthetase 1 (ASS1) expression is increased in gastric cancer. We detected the protein expression of ASS1 in human gastric cancer cell lines (AGS, NCI-N87, and MKN45) and in murine gastric cancer cell lines (3I and 3IB2). We used vector-mediated short hairpin RNA (shRNA) expression to silence ASS1 expression in the MKN45 and 3IB2 cell lines, and analyzed the effects of this protein on cell migration and metastasis. We demonstrated that ASS1 silencing suppressed cell migration in the MKN45 and 3IB2 cell lines. ASS1 knockdown significantly reduced liver metastasis in mice after the intrasplenic implantation of 3IB2 cancer cell clones. To determine whether arginine restriction may represent a therapeutic approach to treat gastric cancer, the sensitivity of tumor cells to arginine depletion was determined in gastric cancer cells. Arginine depletion significantly inhibited cell migration in the gastric cancer cell line. The silencing of ASS1 expression in MKN45 and 3IB2 gastric cancer cells markedly decreased STAT3 protein expression. In conclusion, our results indicate that the ASS1 protein is required for cell migration in gastric cancer cell lines. PMID:25928182

  11. Updates on esophageal and gastric cancers

    PubMed Central

    Gallo, Amy; Cha, Charles

    2006-01-01

    Esophageal and gastric cancers are both common and deadly. Patients present most often after disease progression and survival is therefore poor. Due to demographic variability and recent changes in disease incidence, much emphasis has been placed on studying risk factors for both esophageal and gastric cancers. However, with increasing understanding of these diseases, low survival rates persist and continued intensive studies are necessary to optimize treatment plans. This review article discusses updates in the evolving epidemiology, clinical presentation, risk factors, and diagnostic and treatment modalities of esophageal and gastric cancers. PMID:16718845

  12. Molecular Pathogenesis of Helicobacter pylori-Related Gastric Cancer.

    PubMed

    Shimizu, Takahiro; Marusawa, Hiroyuki; Watanabe, Norihiko; Chiba, Tsutomu

    2015-09-01

    Helicobacter pylori infection plays a crucial role in gastric carcinogenesis. H pylori exerts oncogenic effects on gastric mucosa through complex interaction between bacterial virulence factors and host inflammatory responses. On the other hand, gastric cancer develops via stepwise accumulation of genetic and epigenetic alterations in H pylori-infected gastric mucosa. Recent comprehensive analyses of gastric cancer genomes indicate a multistep process of genetic alterations as well as possible molecular mechanisms of gastric carcinogenesis. Both genetic processes of gastric cancer development and molecular oncogenic pathways related to H pylori infection are important to completely understand the pathogenesis of H pylori-related gastric cancer.

  13. Serological assessment of gastric mucosal atrophy in gastric cancer

    PubMed Central

    2012-01-01

    Background Non-invasive tools for gastric cancer screening and diagnosis are lacking. Serological testing with the detection of pepsinogen 1 (PG1), pepsinogen 2 (PG2) and gastrin 17 (G17) offers the possibility to detect preneoplastic gastric mucosal conditions. Aim of this study was to assess the performance of these serological tests in the presence of gastric neoplasia. Methods Histological and serological samples of 118 patients with gastric cancer have been assessed for tumor specific characteristics (Laurén type, localisation), degree of mucosal abnormalities (intestinal metaplasia, atrophy) and serological parameters (PG1, PG2, PG1/2-ratio, G17, H. pylori IgG, CagA status). Association of the general factors to the different serological values have been statistically analyzed. Results Patients with intestinal type gastric cancer had lower PG1 levels and a lower PG1/2-ratio compared to those with diffuse type cancer (p = 0.003). The serum levels of PG2 itself and G17 were not significantly altered. H. pylori infection in general had no influence on the levels of PG1, PG2 and G17 in the serum of gastric cancer patients. There was a trend towards lower PG1 levels in case of positive CagA-status (p = 0.058). The degree of both intestinal metaplasia and atrophy correlated inversely with serum levels for PG1 and the PG1/2-ratio (p < 0.01). Laurén-specific analysis revealed that this is only true for intestinal type tumors. Univariate ANOVA revealed atrophy and CagA-status as the only independent factors for low PG1 and a low PG1/2-ratio. Conclusions Glandular atrophy and a positive CagA status are determinant factors for decreased pepsinogen 1 levels in the serum of patients with gastric cancer. The serological assessment of gastric atrophy by analysis of serum pepsinogen is only adequate for patients with intestinal type cancer. PMID:22289789

  14. Helicobacter pylori and gastric cancer: Indian enigma.

    PubMed

    Misra, Vatsala; Pandey, Renu; Misra, Sri Prakash; Dwivedi, Manisha

    2014-02-14

    Helicobacter pylori (H. pylori) is a gram negative microaerophilic bacterium which resides in the mucous linings of the stomach. It has been implicated in the causation of various gastric disorders including gastric cancer. The geographical distribution and etiology of gastric cancer differ widely in different geographical regions and H. pylori, despite being labeled as a grade I carcinogen, has not been found to be associated with gastric cancer in many areas. Studies in Asian countries such as Thailand, India, Bangladesh, Pakistan, Iran, Saudi Arabian countries, Israel and Malaysia, have reported a high frequency of H. pylori infection co-existing with a low incidence of gastric cancer. In India, a difference in the prevalence of H. pylori infection and gastric cancer has been noted even in different regions of the country leading to a puzzle when attempting to find the causes of these variations. This puzzle of H. pylori distribution and gastric cancer epidemiology is known as the Indian enigma. In this review we have attempted to explain the Indian enigma using evidence from various Indian studies and from around the globe. This review covers aspects of epidemiology, the various biological strains present in different parts of the country and within individuals, the status of different H. pylori-related diseases and the molecular pathogenesis of the bacterium. PMID:24587625

  15. Helicobacter pylori and gastric cancer: Indian enigma.

    PubMed

    Misra, Vatsala; Pandey, Renu; Misra, Sri Prakash; Dwivedi, Manisha

    2014-02-14

    Helicobacter pylori (H. pylori) is a gram negative microaerophilic bacterium which resides in the mucous linings of the stomach. It has been implicated in the causation of various gastric disorders including gastric cancer. The geographical distribution and etiology of gastric cancer differ widely in different geographical regions and H. pylori, despite being labeled as a grade I carcinogen, has not been found to be associated with gastric cancer in many areas. Studies in Asian countries such as Thailand, India, Bangladesh, Pakistan, Iran, Saudi Arabian countries, Israel and Malaysia, have reported a high frequency of H. pylori infection co-existing with a low incidence of gastric cancer. In India, a difference in the prevalence of H. pylori infection and gastric cancer has been noted even in different regions of the country leading to a puzzle when attempting to find the causes of these variations. This puzzle of H. pylori distribution and gastric cancer epidemiology is known as the Indian enigma. In this review we have attempted to explain the Indian enigma using evidence from various Indian studies and from around the globe. This review covers aspects of epidemiology, the various biological strains present in different parts of the country and within individuals, the status of different H. pylori-related diseases and the molecular pathogenesis of the bacterium.

  16. Preoperative administration of polysaccharide Kureha and reduced plasma transforming growth factor-β in patients with advanced gastric cancer: A randomized clinical trial

    PubMed Central

    YAMASHITA, KEISHI; SAKURAMOTO, SHINICHI; MIENO, HIROAKI; NEMOTO, MASAYUKI; SHIBATA, TOMOTAKA; KATADA, NATSUYA; OHTSUKI, SHIGEAKI; SAKAMOTO, YASUTOSHI; HOSHI, KEIKA; WANG, GUOQIN; HEMMI, OSAMU; SATOH, TOSHIHIKO; KIKUCHI, SHIRO; WATANABE, MASAHIKO

    2015-01-01

    Systemic abrogation of TGF-β signaling results in tumor reduction through cytotoxic T lymphocytes activity in a mouse model. The administration of polysaccharide-Kureha (PSK) into tumor-bearing mice also showed tumor regression with reduced TGF-β. However, there have been no studies regarding the PSK administration to cancer patients and the association with plasma TGF-β. PSK (3 g/day) was administered as a neoadjuvant therapy for 2 weeks before surgery. In total, 31 advanced gastric cancer (AGC) patients were randomly assigned to group A (no neoadjuvant PSK; n=14) or B (neoadjuvant PSK therapy; n=17). Plasma TGF-β was measured pre- and postoperatively. The allocation factors were clinical stage (cStage) and gender. Plasma TGF-β ranged from 1.85–43.5 ng/ml (average, 9.50 ng/ml) in AGC, and 12 patients (38.7%) had a high value, >7.0 ng/ml. These patients were largely composed of poorly-differentiated adenocarcinoma with pathological stage III/IV. All the six elevated cases in group B showed a significant reduction of plasma TGF-β (from 21.6 to 4.5 ng/ml, on average), whereas this was not exhibited in group A. The cases within the normal limits of TGF-β remained unchanged irrespective of PSK treatment. Analysis of variance showed a statistically significant reduction in the difference of plasma TGF-β between groups A and B (P=0.019). PSK reduced the plasma TGF-β in AGC patients when the levels were initially high. The clinical advantage of PSK may, however, be restricted to specific histological types of AGC. Perioperative suppression of TGF-β by PSK may antagonize cancer immune evasion and improve patient prognosis in cases of AGC. PMID:26137253

  17. Environmental and lifestyle risk factors of gastric cancer.

    PubMed

    Lee, Yeong Yeh; Derakhshan, Mohammad H

    2013-06-01

    Effective prevention and early diagnostic strategies are the most important public health interventions in gastric cancer, which remains a common malignancy worldwide. Preventive strategies require identification and understanding of environmental risk factors that lead to carcinogenesis. Helicobacter pylori (H. pylori) is the primary carcinogen as this ancient bacterium has a complex ability to interact with its human host. Smoking and salt are strong independent risk factors for gastric cancer whereas alcohol is only a risk when it is heavily consumed. Red meat and high fat increase the risk of gastric cancer however fresh fruits, vegetables (allium family) and certain micronutrients (selenium, vitamin C) reduce the risk, with evidence lacking for fish, coffee and tea. Foods that inhibit H. pylori viability, colonization and infection may reduce cancer risk. Obesity is increasingly recognized as a contributory factor in gastric cardia carcinogenesis. Therefore, modest daily physical activities can be protective against cancer. Foundry workers are at risk for developing gastric cancer with dust iron being an important cause. Other risk factors include Epstein-Barr virus (EBV), possibly JC virus and radiation but the effects of these are likely to remain small. PMID:23725070

  18. Epigenetic alterations in gastric cancer (Review).

    PubMed

    Fu, Du-Guan

    2015-09-01

    Gastric cancer is one of the most common types of cancer and the second most common cause of cancer-related mortality worldwide. An increasing number of recent studies have confirmed that gastric cancer is a multistage pathological state that arises from environmental factors; dietary factors in particulary are considered to play an important role in the etiology of gastric cancer. Improper dietary habits are one of the primary concerns as they influence key molecular events associated with the onset of gastric carcinogenesis. In the field of genetics, anticancer research has mainly focused on the various genetic markers and genetic molecular mechanisms responsible for the development of this of this disease. Some of this research has proven to be very fruitful, providing insight into the possible mechamisms repsonsible for this disease and into possible treatment modalities. However, the mortality rate associated with gastric cancer remains relatively high. Thus, epigenetics has become a hot topic for research, whereby genetic markers are bypassed and this research is directed towards reversible epigenetic events, such as methylation and histone modifications that play a crucial role in carcinogenesis. The present review focuses on the epigenetic events which play an important role in the development and progression of this deadly disease, gastric cancer.

  19. Pulmonary Resection for Metastatic Gastric Cancer

    PubMed Central

    Akiyama, Hirohiko; Atari, Maiko; Fukuhara, Mitsuro; Nakajima, Yuki; Kinosita, Hiroyasu; Uramoto, Hidetaka

    2016-01-01

    Background: Pulmonary metastasectomy has come to be recognized as an effective treatment for selected patients with some malignancies. On the other hand, the role of pulmonary metastasectomy for gastric cancer is still unknown. Metastasectomy is rarely indicated in cases of pulmonary metastasis from gastric cancer, because in most cases, the metastasis occurs in the form of lymphangitic carcinomatosis and the lesions are numerous. The purpose of this study was to determine the surgical outcomes and prognostic factors for survival after pulmonary metastasectomy. Methods: From 1985 to 2012, 10 patients underwent pulmonary metastasectomy for gastric cancer at Saitama Cancer Center, Japan. The overall survival rate was examined by the Kaplan-Meier method and univariate analysis was carried out to identify prognostic factors. Results: The overall 3-year survival rate was 30.0%. The median follow-up period was 26.8 months (range, 6.5–96.6) after the pulmonary metastasectomy. Univariate analysis revealed an advanced pathological stage of the gastric cancer and occurrence of extrapulmonary metastasis before the pulmonary metastasectomy as unfavorable prognostic factors. Conclusion: Pulmonary metastasectomy should be considered in selected patients with lung metastasis from gastric cancer. An advanced pathological stage of gastric cancer and occurrence of extrapulmonary metastasis before the pulmonary metastasectomy are unfavorable prognostic factors. PMID:27118522

  20. Familial Clustering of Gastric Cancer

    PubMed Central

    Choi, Yoon Jin; Kim, Nayoung; Jang, Woncheol; Seo, Bochang; Oh, Sooyeon; Shin, Cheol Min; Lee, Dong Ho; Jung, Hyun Chae

    2016-01-01

    Abstract This comprehensive cross-sectional study aimed to identify factors contributing to familial aggregation of gastric cancer (GC). A total of 1058 GC patients and 1268 controls were analyzed separately according to the presence or absence of a first-degree relative of GC (GC-relative). Logistic regression analysis adjusted for age, gender, residence during childhood, smoking, alcohol intake, monthly income, spicy food ingestion, Helicobacter pylori status and host cytokine polymorphisms was performed. Cytotoxin-associated gene A (cagA) positivity was a distinctive risk factor for GC in the family history (FH)-positive group (odds ratio [OR], 2.39; 95% confidence interval [CI], 1.42–4.00), while current/ex-smoker, moderate to strong spicy food ingestion, and non-B blood types were more closely associated with GC in the FH-negative group. Among the FH-positive group, alcohol consumption showed a synergistic carcinogenic effect in the at least 2 GC-relatives group compared to the 1 GC-relative group (1.71 vs. 9.58, P for interaction = 0.026), and this was dose-dependent. In the subjects with ≥2 GC-relatives, TGFB1-509T/T was a risk factor for GC (OR 23.74; 95% CI 1.37–410.91), as were rural residency in childhood, alcohol consumption, spicy food ingestion, and cagA positivity. These results suggest that subjects with FH may be a heterogeneous group in terms of gastric cancer susceptibility. Especially, subjects with ≥2 GC-relatives should undergo risk stratification including TGFB1-509T/T and alcohol consumption. PMID:27196462

  1. Genetics Home Reference: hereditary diffuse gastric cancer

    MedlinePlus

    ... JT, van Hillegersberg R, Dekker E, Oliveira C, Cats A, Hoogerbrugge N; Dutch Working Group on Hereditary ... JH, van Hillegersberg R, Ligtenberg M, Bleiker E, Cats A; Dutch Working Group on Hereditary Gastric Cancer. ...

  2. [Cancer of the gastric stump: our experience].

    PubMed

    Vecchioni, R; Rossi, M

    1990-01-01

    The experienced gained over the past few years in the Verona University Institute of Surgical Pathology has revealed a slow, though progressive, increase in the number of gastric stump cancers, reflecting a trend emerging in the literature. There can be no doubt that an important factor in the enhanced detection of such cancers is the adoption of digestive endoscopy in routine clinical practice. Silent symptoms, barely noticeable clinical signs and the particular aggressiveness of the tumours often lead to an excessively late diagnosis, which, unfortunately, limits the efficacy of surgical therapy. We therefore recommend, as a single solution to the problem, the endoscopic screening of all patients who have undergone gastric resection ten or more years ago in order to detect early stump cancer. Obviously, and fortunately, in a few years time gastric stump cancer will be a rare phenomenon, in view of the exponential drop in gastric resections for ulcer disease over the past decade.

  3. Hematogenous Gastric Metastasis of Pancreatic Cancer

    PubMed Central

    Sasajima, Junpei; Okamoto, Kotaro; Taniguchi, Masato

    2016-01-01

    While the gastric involvement of pancreatic cancer is occasionally observed as the result of direct invasion, hematogenous gastric metastasis is rare. A 72-year-old Japanese male presented with general fatigue, pollakiuria, and thirst. Computed tomography revealed a 4.6-cm solid mass in the pancreatic tail and a 4.2-cm multilocular cystic mass in the pancreatic head with multiple liver and lymphatic metastasis. Notably, two solid masses were detected in the gastric wall of the upper body and the antrum; both were separated from the primary pancreatic cancer and seemed to be located in the submucosal layer. Esophagogastroduodenoscopy revealed a submucosal tumor with a normal mucosa in the posterior wall of the upper body of the stomach, suggesting the gastric hematogenous metastasis of pancreatic cancer. The suspected diagnosis was unresectable pancreatic cancer with multiple metastases that was concomitant with the intraductal papillary mucinous neoplasm of the pancreas. PMID:27403106

  4. Hematogenous Gastric Metastasis of Pancreatic Cancer.

    PubMed

    Sasajima, Junpei; Okamoto, Kotaro; Taniguchi, Masato

    2016-01-01

    While the gastric involvement of pancreatic cancer is occasionally observed as the result of direct invasion, hematogenous gastric metastasis is rare. A 72-year-old Japanese male presented with general fatigue, pollakiuria, and thirst. Computed tomography revealed a 4.6-cm solid mass in the pancreatic tail and a 4.2-cm multilocular cystic mass in the pancreatic head with multiple liver and lymphatic metastasis. Notably, two solid masses were detected in the gastric wall of the upper body and the antrum; both were separated from the primary pancreatic cancer and seemed to be located in the submucosal layer. Esophagogastroduodenoscopy revealed a submucosal tumor with a normal mucosa in the posterior wall of the upper body of the stomach, suggesting the gastric hematogenous metastasis of pancreatic cancer. The suspected diagnosis was unresectable pancreatic cancer with multiple metastases that was concomitant with the intraductal papillary mucinous neoplasm of the pancreas. PMID:27403106

  5. Molecular classification of gastric cancer.

    PubMed

    Chia, N-Y; Tan, P

    2016-05-01

    Gastric cancer (GC), a heterogeneous disease characterized by epidemiologic and histopathologic differences across countries, is a leading cause of cancer-related death. Treatment of GC patients is currently suboptimal due to patients being commonly treated in a uniform fashion irrespective of disease subtype. With the advent of next-generation sequencing and other genomic technologies, GCs are now being investigated in great detail at the molecular level. High-throughput technologies now allow a comprehensive study of genomic and epigenomic alterations associated with GC. Gene mutations, chromosomal aberrations, differential gene expression and epigenetic alterations are some of the genetic/epigenetic influences on GC pathogenesis. In addition, integrative analyses of molecular profiling data have led to the identification of key dysregulated pathways and importantly, the establishment of GC molecular classifiers. Recently, The Cancer Genome Atlas (TCGA) network proposed a four subtype classification scheme for GC based on the underlying tumor molecular biology of each subtype. This landmark study, together with other studies, has expanded our understanding on the characteristics of GC at the molecular level. Such knowledge may improve the medical management of GC in the future. PMID:26861606

  6. Helicobacter pylori, Cancer, and the Gastric Microbiota.

    PubMed

    Wroblewski, Lydia E; Peek, Richard M

    2016-01-01

    Gastric adenocarcinoma is one of the leading causes of cancer-related death worldwide and Helicobacter pylori infection is the strongest known risk factor for this disease. Although the stomach was once thought to be a sterile environment, it is now known to house many bacterial species leading to a complex interplay between H. pylori and other residents of the gastric microbiota. In addition to the role of H. pylori virulence factors, host genetic polymorphisms, and diet, it is now becoming clear that components of the gastrointestinal microbiota may also influence H. pylori-induced pathogenesis. In this chapter, we discuss emerging data regarding the gastric microbiota in humans and animal models and alterations that occur to the composition of the gastric microbiota in the presence of H. pylori infection that may augment the risk of developing gastric cancer. PMID:27573782

  7. Robot-assisted surgery for gastric cancer

    PubMed Central

    Procopiuc, Livia; Tudor, Ştefan; Mănuc, Mircea; Diculescu, Mircea; Vasilescu, Cătălin

    2016-01-01

    Minimally invasive surgery for gastric cancer is a relatively new research field, with convincing results mostly stemming from Asian countries. The use of the robotic surgery platform, thus far assessed as a safe procedure, which is also easier to learn, sets the background for a wider spread of minimally invasive technique in the treatment of gastric cancer. This review will cover the literature published so far, analyzing the pros and cons of robotic surgery and highlighting the remaining study questions. PMID:26798433

  8. Inhibition of PRL-3 gene expression in gastric cancer cell line SGC7901 via microRNA suppressed reduces peritoneal metastasis

    SciTech Connect

    Li Zhengrong; Zhan Wenhua . E-mail: wcywk@hotmail.com; Wang Zhao; Zhu Baohe; He Yulong; Peng Junsheng; Cai Shirong; Ma Jinping

    2006-09-15

    High expression of PRL-3, a protein tyrosine phosphatase, is proved to be associated with lymph node metastasis in gastric carcinoma from previous studies. In this paper, we examined the relationship between PRL-3 expression and peritoneal metastasis in gastric carcinoma. We applied the artificial miRNA (pCMV-PRL3miRNA), which is based on the murine miR-155 sequence, to efficiently silence the target gene expression of PRL-3 in SGC7901 gastric cancer cells at both mRNA and protein levels. Then we observed that, in vitro, pCMV-PRL3miRNA significantly depressed the SGC7901 cell invasion and migration independent of cellular proliferation. In vivo, PRL-3 knockdown effectively suppressed the growth of peritoneal metastases and improved the prognosis in nude mice. Therefore, we concluded that artificial miRNA can depress the expression of PRL-3, and that PRL-3 might be a potential therapeutic target for gastric cancer peritoneal metastasis.

  9. VEGF promotes gastric cancer development by upregulating CRMP4

    PubMed Central

    Peng, Jianjun; Zhai, Ertao; He, Yulong; Wu, Hui; Chen, Chuangqi; Ma, Jinping; Wang, Zhao; Cai, Shirong

    2016-01-01

    This study aimed to investigate the precise role of CRMP4 in gastric tumor growth and patient survival. The mRNA and protein expression levels of CRMP4, VEGF and VEGFR2 were validated by qRT-PCR and immunohistochemistry. We investigated the effects on tumor growth of overexpression and knockdown of CRMP4 both in vitro and in vivo by constructing stable gastric cell lines using lentiviral-mediated transduction and shRNA interference-mediated knockdown of CRMP4 expression. We further validated the role of the ERK/AKT signaling pathways in VEGF and CRMP4 expression using ERK and PI3K inhibitors. Increased expression of VEGF and CRMP4 were observed in gastric cancer tissues compared with tumor-adjacent tissue. We found that higher CRPM4 expression was associated with lymph node metastasis, TNM stage, tumor differentiation and poorer prognosis in gastric cancer patients. In HGC27 and SGC7901 gastric cancer cells, VEGF upregulated CRMP4 in time and dose-dependent manners. Overexpression of CRMP4 increased cell proliferation, migration and invasion, whereas knockdown of CRMP4 expression had opposite effects. VEGF activated CRMP4 expression in gastric cancer cells, and this effect was significantly inhibited by MAPK and PI3K inhibitors (PD98059 and LY294002). In mice, CRMP4 overexpression also resulted in increased tumor growth. These results suggest that increased CRMP4 expression mediated by the activation of VEGF signaling facilitates gastric tumor growth and metastasis, which may have clinical implications associated with a reduced survival rate in gastric cancer patients. PMID:26934554

  10. Gastric Intestinal Metaplasia and Early Gastric Cancer in the West: A Changing Paradigm

    PubMed Central

    Gomez, Justin M.

    2014-01-01

    Gastric cancer remains the fifth leading cancer diagnosis worldwide, and it is the third leading cause of cancer-related mortality. The incidence of gastric cancer within the United States, however, has remained substantially lower than elsewhere, which has led to a lack of screening and surveillance in clinical practice. Patients with known premalignant lesions, such as gastric intestinal metaplasia, which can increase the risk of gastric cancer by as much as 6-fold, might benefit from surveillance guidelines to detect gastric cancer at an earlier, potentially curative stage. Chro-moendoscopy with optical magnification, narrow-band imaging, and other image-enhanced endoscopic techniques are commercially available to assist in the diagnosis of premalignant gastric lesions and early gastric cancer. Furthermore, endoscopic mucosal resection and endoscopic submucosal dissection have become more widely available and offer potentially curative endoscopic resection for dysplastic lesions of the stomach and early gastric cancers, which is an alternative to traditional surgical resection. PMID:25013389

  11. Multidisciplinary management for esophageal and gastric cancer.

    PubMed

    Boniface, Megan M; Wani, Sachin B; Schefter, Tracey E; Koo, Phillip J; Meguid, Cheryl; Leong, Stephen; Kaplan, Jeffrey B; Wingrove, Lisa J; McCarter, Martin D

    2016-01-01

    The management of esophageal and gastric cancer is complex and involves multiple specialists in an effort to optimize patient outcomes. Utilizing a multidisciplinary team approach starting from the initial staging evaluation ensures that all members are in agreement with the plan of care. Treatment selection for esophageal and gastric cancer often involves a combination of chemotherapy, radiation, surgery, and palliative interventions (endoscopic and surgical), and direct communication between specialists in these fields is needed to ensure appropriate clinical decision making. At the University of Colorado, the Esophageal and Gastric Multidisciplinary Clinic was created to bring together all experts involved in treating these diseases at a weekly conference in order to provide patients with coordinated, individualized, and patient-centered care. This review details the essential elements and benefits of building a multidisciplinary program focused on treating esophageal and gastric cancer patients.

  12. Multidisciplinary management for esophageal and gastric cancer

    PubMed Central

    Boniface, Megan M; Wani, Sachin B; Schefter, Tracey E; Koo, Phillip J; Meguid, Cheryl; Leong, Stephen; Kaplan, Jeffrey B; Wingrove, Lisa J; McCarter, Martin D

    2016-01-01

    The management of esophageal and gastric cancer is complex and involves multiple specialists in an effort to optimize patient outcomes. Utilizing a multidisciplinary team approach starting from the initial staging evaluation ensures that all members are in agreement with the plan of care. Treatment selection for esophageal and gastric cancer often involves a combination of chemotherapy, radiation, surgery, and palliative interventions (endoscopic and surgical), and direct communication between specialists in these fields is needed to ensure appropriate clinical decision making. At the University of Colorado, the Esophageal and Gastric Multidisciplinary Clinic was created to bring together all experts involved in treating these diseases at a weekly conference in order to provide patients with coordinated, individualized, and patient-centered care. This review details the essential elements and benefits of building a multidisciplinary program focused on treating esophageal and gastric cancer patients. PMID:27217796

  13. Recent developments and innovations in gastric cancer

    PubMed Central

    Mihmanli, Mehmet; Ilhan, Enver; Idiz, Ufuk Oguz; Alemdar, Ali; Demir, Uygar

    2016-01-01

    Gastric cancer has an important place in the worldwide incidence of cancer and cancer-related deaths. It can metastasize to the lymph nodes in the early stages, and lymph node metastasis is an important prognostic factor. Surgery is a very important part of gastric cancer treatment. A D2 lymphadenectomy is the standard surgical treatment for cT1N+ and T2-T4 cancers, which are potentially curable. Recently, the TNM classification system was reorganized, and the margins for gastrectomy and lymphadenectomy were revised. Endoscopic, laparoscopic and robotic treatments of gastric cancer have progressed rapidly with development of surgical instruments and techniques, especially in Eastern countries. Different endoscopic resection techniques have been identified, and these can be divided into two main categories: endoscopic mucosal resection and endoscopic submucosal dissection. Minimally invasive surgery has been reported to be safe and effective for early gastric cancer, and it can be successfully applied to advanced gastric cancer with increasing experience. Cytoreductive surgery and hyperthermıc intraperıtoneal chemotherapy were developed as a combined treatment modality from the results of experimental and clinical studies. Also, hyperthermia increases the antitumor activity and penetration of chemotherapeutics. Trastuzumab which is a monoclonal antibody interacts with human epidermal growth factor (HER) 2 and is related to gastric carcinoma. The anti-tumor mechanism of trastuzumab is not clearly known, but mechanisms such as interruption of the HER2-mediated cell signaling pathways and cell cycle progression have been reported previously. H. pylori is involved in 90% of all gastric malignancies and Japanese guidelines strongly recommend that all H. pylori infections should be eradicated regardless of the associated disease. In this review, we present innovations discussed in recent studies. PMID:27158199

  14. Molecular characterization of the stomach microbiota in patients with gastric cancer and controls

    SciTech Connect

    Dicksved, J.; Lindberg, M.; Rosenquist, M.; Enroth, H.; Jansson, J.K.; Engstrand, L.

    2009-01-15

    Persistent infection of the gastric mucosa by Helicobacter pylori, can initiate an inflammatory cascade that progresses into atrophic gastritis, a condition associated with reduced capacity for secretion of gastric acid and an increased risk in developing gastric cancer. The role of H. pylori as an initiator of inflammation is evident but the mechanism for development into gastric cancer has not yet been proven. A reduced capacity for gastric acid secretion allows survival and proliferation of other microbes that normally are killed by the acidic environment. It has been postulated that some of these species may be involved in the development of gastric cancer, however their identities are poorly defined. In this study, the gastric microbiota from ten patients with gastric cancer was characterized and compared with five dyspeptic controls using the molecular profiling approach, terminal-restriction fragment length polymorphism (T-RFLP), in combination with 16S rRNA gene cloning and sequencing. T-RFLP analysis revealed a complex bacterial community in the cancer patients that was not significantly different from the controls. Sequencing of 140 clones revealed 102 phylotypes, with representatives from five bacterial phyla (Firmicutes, Bacteroidetes, Proteobacteria, Actinobacteria and Fusobacteria). The data revealed a relatively low abundance of H. pylori and showed that the gastric cancer microbiota was instead dominated by different species of the genera Streptococcus, Lactobacillus, Veillonella and Prevotella. The respective role of these species in development of gastric cancer remains to be determined.

  15. [New insights in the adjuvant treatment of gastric cancer].

    PubMed

    Jansen, E P M; Boot, H; Cats, A; van Coevorden, F; Zoetmulder, F A N; Verheij, M

    2004-12-18

    The current standard treatment of patients with gastric cancer is partial or total stomach resection and dissection of the draining lymph nodes. This approach, however, results in a rather low survival rate, partly because the diagnosis is often established in an advanced stage. Various strategies, including adjuvant radiotherapy, chemotherapy or more extensive surgical procedures, have resulted mainly in increased morbidity without improving survival. In a recent randomised trial, concurrent postoperative radiotherapy and chemotherapy prolonged survival and reduced the chance of a local recurrence at an acceptable toxicity. Although several aspects of combined radiochemotherapy require further study, this new treatment concept appears to be a promising addition to the therapeutic arsenal for gastric cancer.

  16. Endoscopic Gastric Cancer Screening and Surveillance in High-Risk Groups

    PubMed Central

    2014-01-01

    Gastric cancer remains a major cancer problem world-wide and future incidence will likely increase due to rapidly aging population demographics. Population-based screening is being undertaken in Korea and Japan, where gastric cancer incidence rates are high, and seems to be effective in reducing mortality from gastric cancer. However, such strategies are difficult to implement in countries with a low incidence or limited resources. Thus, screening strategies should be directed towards high-risk population subgroups. Gastric cancer has a relatively long mean sojourn time, and prognosis of early-stage disease is excellent. In general population, screening at 2-year interval in Korea seems to be effective for early-stage diagnosis. In subjects with atrophic gastritis or intestinal metaplasia, surveillance is recommended at 1 to 3 years intervals according to European and Japanese recommendation. Screening intervals for family members with sporadic gastric cancer has not yet been adequately evaluated, but 1-year interval is recommended for hereditary diffuse gastric cancer family-members. Gastric cancer patients treated by endoscopic resection are the highest-risk group, and 1-year interval surveillance can detect most metachronous gastric cancers at an early stage. Future gastric cancer surveillance strategies using endoscopy should be guided by risk-stratification assessment, and further refinement of optimal surveillance intervals is needed. PMID:25505714

  17. Immunotherapy for gastric premalignant lesions and cancer.

    PubMed

    Zorzetto, Valerio; Maddalo, Gemma; Basso, Daniela; Farinati, Fabio

    2012-06-01

    Chronic atrophic gastritis, a precancerous change for gastric cancer, shows a loss of appropriate glands, Helicobacter pylori infection and autoimmune gastritis being the two main etiologic factors. While H. pylori eradication is the mandatory treatment for the former, no etiologic treatment is available for the latter, in which a Th1-type response, modulated by Tregs and Th17 cells, is involved. H. pylori-related atrophic gastritis is a risk factor for gastric adenocarcinoma, while autoimmune atrophic gastritis is also linked to a substantial risk of gastric type I carcinoid, related to the chronic stimulus exerted by hypergastrinemia on enterochromaffin-like cells. Several studies have been published on gastric cancer treatment through an active specific immunotherapy, aimed at improving the immunoregulatory response and increasing the circulating tumor-specific T cells. No study on immunotherapy of carcinoids is available but, in our experience, the administration of an antigastrin 17 vaccine induced carcinoid regression in two out of three patients treated.

  18. Helicobacter Pylori associated global gastric cancer burden

    PubMed Central

    Mbulaiteye, Sam M.; Hisada, Michie; El-Omar, Emad M.

    2008-01-01

    1. Abstract Helicobacter pylori infection is ubiquitous, infecting close to one-half of the world's population, but its prevalence is declining in developed countries. Chronic H. pylori infection is etiologically linked to gastric adenocarcinoma, especially non-cardia type (63% of all stomach cancer or ∼5.5% of the global cancer burden: ∼25% of cancers associated with infectious etiology), and to gastric mucosal associated lymphoid tissue (MALT) lymphoma, which accounts for up to 8% of all non-Hodgkin lymphoma. Epidemiological, clinical, and animal studies have established a central role for H. pylori in gastric carcinogenesis and provided insights into the mechanisms and biologic relationships between bacterial infection, host genetics, nutrition, and environmental factors. These discoveries invite strategies to prevent infection to be the logical primary goals in a multi-pronged effort to curtail suffering and death from H. pylori infection-associated cancers. PMID:19273142

  19. Challenges of deciphering gastric cancer heterogeneity.

    PubMed

    Hudler, Petra

    2015-10-01

    Gastric cancer is in decline in most developed countries; however, it still accounts for a notable fraction of global mortality and morbidity related to cancer. High-throughput methods are rapidly changing our view and understanding of the molecular basis of gastric carcinogenesis. Today, it is widely accepted that the molecular complexity and heterogeneity, both inter- and intra-tumour, of gastric adenocarcinomas present significant obstacles in elucidating specific biomarkers for early detection of the disease. Although genome-wide sequencing and gene expression studies have revealed the intricate nature of the molecular changes that occur in tumour landscapes, the collected data and results are complex and sometimes contradictory. Several aberrant molecules have already been tested in clinical trials, although their diagnostic and prognostic utilities have not been confirmed thus far. The gold standard for the detection of sporadic gastric cancer is still the gastric endoscopy, which is considered invasive. In addition, genome-wide association studies have confirmed that genetic variations are important contributors to increased cancer risk and could participate in the initiation of malignant transformation. This hypothesis could in part explain the late onset of sporadic gastric cancers. The elaborate interplay of polymorphic low penetrance genes and lifestyle and environmental risk factors requires additional research to decipher their relative impacts on tumorigenesis. The purpose of this article is to present details of the molecular heterogeneity of sporadic gastric cancers at the DNA, RNA, and proteome levels and to discuss issues relevant to the translation of basic research data to clinically valuable tools. The focus of this work is the identification of relevant molecular changes that could be detected non-invasively. PMID:26457012

  20. Challenges of deciphering gastric cancer heterogeneity

    PubMed Central

    Hudler, Petra

    2015-01-01

    Gastric cancer is in decline in most developed countries; however, it still accounts for a notable fraction of global mortality and morbidity related to cancer. High-throughput methods are rapidly changing our view and understanding of the molecular basis of gastric carcinogenesis. Today, it is widely accepted that the molecular complexity and heterogeneity, both inter- and intra-tumour, of gastric adenocarcinomas present significant obstacles in elucidating specific biomarkers for early detection of the disease. Although genome-wide sequencing and gene expression studies have revealed the intricate nature of the molecular changes that occur in tumour landscapes, the collected data and results are complex and sometimes contradictory. Several aberrant molecules have already been tested in clinical trials, although their diagnostic and prognostic utilities have not been confirmed thus far. The gold standard for the detection of sporadic gastric cancer is still the gastric endoscopy, which is considered invasive. In addition, genome-wide association studies have confirmed that genetic variations are important contributors to increased cancer risk and could participate in the initiation of malignant transformation. This hypothesis could in part explain the late onset of sporadic gastric cancers. The elaborate interplay of polymorphic low penetrance genes and lifestyle and environmental risk factors requires additional research to decipher their relative impacts on tumorigenesis. The purpose of this article is to present details of the molecular heterogeneity of sporadic gastric cancers at the DNA, RNA, and proteome levels and to discuss issues relevant to the translation of basic research data to clinically valuable tools. The focus of this work is the identification of relevant molecular changes that could be detected non-invasively. PMID:26457012

  1. RNA interference targeting raptor inhibits proliferation of gastric cancer cells

    SciTech Connect

    Wu, William Ka Kei; Lee, Chung Wa; Cho, Chi Hin; Chan, Francis Ka Leung; Yu, Jun; Sung, Joseph Jao Yiu

    2011-06-10

    Mammalian target of rapamycin complex 1 (mTORC1) is dysregulated in gastric cancer. The biologic function of mTORC1 in gastric carcinogenesis is unclear. Here, we demonstrate that disruption of mTORC1 function by RNA interference-mediated downregulation of raptor substantially inhibited gastric cancer cell proliferation through induction of G{sub 0}/G{sub 1}-phase cell cycle arrest. The anti-proliferative effect was accompanied by concomitant downregulation of activator protein-1 and upregulation of Smad2/3 transcriptional activities. In addition, the expression of cyclin D{sub 3} and p21{sup Waf1}, which stabilizes cyclin D/cdk4 complex for G{sub 1}-S transition, was reduced by raptor knockdown. In conclusion, disruption of mTORC1 inhibits gastric cancer cell proliferation through multiple pathways. This discovery may have an implication in the application of mTORC1-directed therapy for the treatment of gastric cancer.

  2. New advances in targeted gastric cancer treatment.

    PubMed

    Lazăr, Daniela Cornelia; Tăban, Sorina; Cornianu, Marioara; Faur, Alexandra; Goldiş, Adrian

    2016-08-14

    Despite a decrease in incidence over past decades, gastric cancer remains a major global health problem. In the more recent period, survival has shown only minor improvement, despite significant advances in diagnostic techniques, surgical and chemotherapeutic approaches, the development of novel therapeutic agents and treatment by multidisciplinary teams. Because multiple genetic mutations, epigenetic alterations, and aberrant molecular signalling pathways are involved in the development of gastric cancers, recent research has attempted to determine the molecular heterogeneity responsible for the processes of carcinogenesis, spread and metastasis. Currently, some novel agents targeting a part of these dysfunctional molecular signalling pathways have already been integrated into the standard treatment of gastric cancer, whereas others remain in phases of investigation within clinical trials. It is essential to identify the unique molecular patterns of tumours and specific biomarkers to develop treatments targeted to the individual tumour behaviour. This review analyses the global impact of gastric cancer, as well as the role of Helicobacter pylori infection and the efficacy of bacterial eradication in preventing gastric cancer development. Furthermore, the paper discusses the currently available targeted treatments and future directions of research using promising novel classes of molecular agents for advanced tumours. PMID:27570417

  3. New advances in targeted gastric cancer treatment

    PubMed Central

    Lazăr, Daniela Cornelia; Tăban, Sorina; Cornianu, Marioara; Faur, Alexandra; Goldiş, Adrian

    2016-01-01

    Despite a decrease in incidence over past decades, gastric cancer remains a major global health problem. In the more recent period, survival has shown only minor improvement, despite significant advances in diagnostic techniques, surgical and chemotherapeutic approaches, the development of novel therapeutic agents and treatment by multidisciplinary teams. Because multiple genetic mutations, epigenetic alterations, and aberrant molecular signalling pathways are involved in the development of gastric cancers, recent research has attempted to determine the molecular heterogeneity responsible for the processes of carcinogenesis, spread and metastasis. Currently, some novel agents targeting a part of these dysfunctional molecular signalling pathways have already been integrated into the standard treatment of gastric cancer, whereas others remain in phases of investigation within clinical trials. It is essential to identify the unique molecular patterns of tumours and specific biomarkers to develop treatments targeted to the individual tumour behaviour. This review analyses the global impact of gastric cancer, as well as the role of Helicobacter pylori infection and the efficacy of bacterial eradication in preventing gastric cancer development. Furthermore, the paper discusses the currently available targeted treatments and future directions of research using promising novel classes of molecular agents for advanced tumours. PMID:27570417

  4. Helicobacter pylori and gastric cancer: current status of the Austrain-Czech-German gastric cancer prevention trial (PRISMA-Study)

    PubMed Central

    Miehlke, S.; Kirsch, C.; Dragosics, B.; Gschwantler, M.; Oberhuber, G.; Antos, D.; Dite, P.; Luter, J.; Labenz, J.; Leodolter, A.; Malfertheiner, P.; Neubauer, A.; Ehninger, G.; Stolte, M.; rffer, E. Bayerdö

    2001-01-01

    AIM: To test the hypothesis that Helicobacter pylori eradication alone can reduce the incidence of gastric cancer in a subgroup of individuals with an increased risk for this fatal disease. METHODS: It is a prospective, randomized, double blind, placebo controlled multinational multicenter trial. Men between 55 and 65 years of age with a gastric cancer phenotype of Helicobacter pylori gastritis are randomized to receive a 7 day course of omeprazole 2 × 20 mg, clarithromycin 2 × 500 mg, and amoxicillin 2 × 1 g for 7 days, or omeprazole 2 × 20 mg plus placebo. Follow-up endoscopy is scheduled 3 months after therapy, and thereafter in one-year intervals. Predefined study endpoints are gastric cancer, precancerous lesions (dysplasia, adenoma), other cancers, and death. RESULTS: Since March 1998, 1524 target patients have been screened, 279 patients (18.3%) had a corpus dominant type of H. pylori gastritis, and 167 of those were randomized (58.8%). In the active treatment group (n = 86), H. pylori infection infection was cured in 88.9% of patients. Currently, the cumulative follow-up time is 3046 months (253. 38 patient years, median follow up 16 months). So far, none of the patients developed gastric cancer or any precancerous lesion. Three (1.8%) patients reached study endpoints other than gastric cancer. CONCLUSION: Among men between 55 and 65 years of age, the gastric cancer phenotype of H. pylori gastritis appears to be more common than expected. Further follow up and continuing recruitment are necessary to fulfil the main aim of the study. PMID:11819768

  5. Hereditary diffuse gastric cancer--An overview.

    PubMed

    Gurzu, Simona; Jung, Ioan; Orlowska, Janina; Sugimura, Haruhiko; Kadar, Zoltan; Turdean, Sabin; Bara, Tivadar

    2015-09-01

    The incidence of gastric cancer varies by up to ten fold throughout the world, and the geographic distribution of hereditary cases is not well explored. Familial clustering is seen in 10% of cases, and approximately 3% of all gastric cancers develop due to hereditary diffuse gastric cancer (HDGC). In this review, the characteristics of HDGC are presented according to molecular particularities, geographic distribution, and other parameters. Based on our experience and the data from the literature, we discuss the possibility of applying a mutation signature (spectrum) study and adductomic approaches to a comparative carcinogenesis of HDGC. We also provide a comprehensive, up-to-date review of genetic counseling and criteria for screening and surveillance of eligible families.

  6. Familial gastric and pancreatic cancers: Diagnosis and screening.

    PubMed

    Raymond, Victoria M; Stoffel, Elena M

    2013-01-01

    Screening for gastric and pancreatic cancers in asymptomatic individuals is not routinely practiced in the United States. While there is insufficient evidence that general population screening would reduce morbidity and/or mortality associated with these cancers, the utility of screening for individuals at increased risk warrants further study. Clinical challenges include identifying high risk individuals who would be most likely to benefit from screening and determining which screening modalities and intervals would be most effective.

  7. Survivin inhibitor YM155 suppresses gastric cancer xenograft growth in mice without affecting normal tissues

    PubMed Central

    Cheng, Xiao Jiao; Lin, Jia Cheng; Ding, Yan Fei; Zhu, Liming; Ye, Jing; Tu, Shui Ping

    2016-01-01

    Survivin overexpression is associated with poor prognosis of human gastric cancer, and is a target for gastric cancer therapy. YM155 is originally identified as a specific inhibitor of survivin. In this study, we investigated the antitumor effect of YM155 on human gastric cancer. Our results showed that YM155 treatment significantly inhibited cell proliferation, reduced colony formation and induced apoptosis of gastric cancer cells in a dose-dependent manner. Accordingly, YM155 treatment significantly decreased survivin expression without affecting XIAP expression and increased the cleavage of apoptosis-associated proteins caspase 3, 7, 8, 9. YM155 significantly inhibited sphere formation of gastric cancer cells, suppressed expansion and growth of the formed spheres (cancer stem cell-like cells, CSCs) and downregulated the protein levels of β-catenin, c-Myc, Cyclin D1 and CD44 in gastric cancer cells. YM155 infusion at 5 mg/kg/day for 7 days markedly inhibited growth of gastric cancer xenograft in a nude mouse model. Immunohistochemistry staining and Western Blot showed that YM155 treatment inhibited expression of survivin and CD44, induced apoptosis and reduced CD44+ CSCs in xenograft tumor tissues in vivo. No obvious pathological changes were observed in organs (e.g. heart, liver, lung and kidney) in YM155-treated mice. Our results demonstrated that YM155 inhibits cell proliferation, induces cell apoptosis, reduces cancer stem cell expansion, and inhibits xenograft tumor growth in gastric cancer cells. Our results elucidate a new mechanism by which YM155 inhibits gastric cancer growth by inhibition of CSCs. YM155 may be a promising agent for gastric cancer treatment. PMID:26771139

  8. Gastric cancer: current and evolving treatment landscape.

    PubMed

    Sun, Weijing; Yan, Li

    2016-01-01

    Gastric (including gastroesophageal junction) cancer is the third leading cause of cancer-related death in the world. In China, an estimated 420,000 patients were diagnosed with gastric cancer in 2011, ranking this malignancy the second most prevalent cancer type and resulting in near 300,000 deaths. The treatment landscape of gastric cancer has evolved in recent years. Although systemic chemotherapy is still the mainstay treatment of metastatic disease, the introduction of agents targeting human epidermal growth factor receptor 2 and vascular endothelial growth factor/vascular endothelia growth factor receptor has brought this disease into the molecular and personalized medicine era. The preliminary yet encouraging clinical efficacy observed with immune checkpoint inhibitors, e.g., anti-programmed cell death protein 1/programmed death-ligand 1, will further shape the treatment landscape for gastric cancer. Molecular characterization of patients will play a critical role in developing new agents, as well as in implementing new treatment options for this disease. PMID:27581465

  9. [Familial gastric cancer: diagnosis, treatment and periodic surveillance].

    PubMed

    Kluijt, Irma; Sijmons, Rolf H; Hoogerbrugge, Nicoline; Vasen, Hans F A; Cats, Anemieke

    2011-01-01

    The only known genetic causes of hereditary diffuse gastric cancer (HDGC) are germline mutations in the CDH1 gene.- CDH1 mutation carriers have a lifetime risk of 70-80% of developing diffuse gastric cancer. As periodic gastric surveillance is of limited value in detecting early stages of HDGC, prophylactic gastrectomy is advised for this patient group. This group is small and little is known about other types of familial gastric cancer. The Dutch Working Group on Hereditary Gastric Cancer has formulated criteria for various aspects of medical care for families and individuals at high risk of developing gastric cancer, including criteria for diagnostics and periodic gastric surveillance. In order to optimize the care and increase the knowledge on hereditary gastric cancer it is important to centralize medical care for these patients.

  10. Osteogenesis Imperfecta, Pseudoachalasia, and Gastric Cancer

    PubMed Central

    Mizrak, Dilsa; Alkan, Ali; Erdogdu, Batuhan; Utkan, Gungor

    2015-01-01

    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. PMID:25874139

  11. Identifying module biomarkers from gastric cancer by differential correlation network

    PubMed Central

    Liu, Xiaoping; Chang, Xiao

    2016-01-01

    Gastric cancer (stomach cancer) is a severe disease caused by dysregulation of many functionally correlated genes or pathways instead of the mutation of individual genes. Systematic identification of gastric cancer biomarkers can provide insights into the mechanisms underlying this deadly disease and help in the development of new drugs. In this paper, we present a novel network-based approach to predict module biomarkers of gastric cancer that can effectively distinguish the disease from normal samples. Specifically, by assuming that gastric cancer has mainly resulted from dysfunction of biomolecular networks rather than individual genes in an organism, the genes in the module biomarkers are potentially related to gastric cancer. Finally, we identified a module biomarker with 27 genes, and by comparing the module biomarker with known gastric cancer biomarkers, we found that our module biomarker exhibited a greater ability to diagnose the samples with gastric cancer. PMID:27703371

  12. The Role of Hyperthermic Intraperitoneal Chemotherapy in Gastric Cancer.

    PubMed

    Seshadri, Ramakrishnan Ayloor; Glehen, Olivier

    2016-06-01

    Peritoneal metastasis, either synchronous or metachronous, is commonly seen in gastric cancer. It is associated with a poor prognosis, with a median survival of less than one year. The outcomes are not significantly improved by the use of systemic chemotherapy. We review the relevant literature on the role of HIPEC in gastric cancer. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has been used in three situations in gastric cancer. Besides its role as a definitive treatment in patients with established peritoneal metastasis (PM), it has been used as a prophylaxis against peritoneal recurrence after curative surgery and also as a palliative treatment in advanced peritoneal metastasis with intractable ascites. While prophylactic HIPEC has been shown to reduce peritoneal recurrence and improve survival in many randomised trials, palliative HIPEC can reduce the need for frequent paracentesis. Although CRS with HIPEC has shown promise in increasing the survival of selected patients with established PM from gastric cancer, larger studies are needed before this can be accepted as a standard of care. PMID:27065710

  13. Adjuvant Treatment for Gastric Cancer: Chemotherapy Versus Radiation

    PubMed Central

    Ashraf, Noman; Hoffe, Sarah

    2013-01-01

    Gastric cancer is among the leading causes of cancer death worldwide. Surgery is the only curative modality, but mortality remains high because a significant number of patients have recurrence after complete surgical resection. Chemotherapy, radiation, and chemoradiotherapy have all been studied in an attempt to reduce the risk for relapse and improve survival. There is no globally accepted standard of care for resectable gastric cancer, and treatment strategies vary across the world. Postoperative chemoradiation with 5-fluorouracil/leucovorin is most commonly practiced in the United States; however, recent clinical trials from Asia have shown benefit of adjuvant chemotherapy alone and have questioned the role of radiation. In this review, we examine the current literature on adjuvant treatment of gastric cancer and discuss the roles of radiation and chemotherapy, particularly in light of these new data and their applicability to the Western population. We highlight some of the ongoing and planned clinical trials in resectable gastric cancer and identify future directions as well as areas where further research is needed. PMID:23966224

  14. Helicobacter pylori Eradication to Eliminate Gastric Cancer: The Japanese Strategy.

    PubMed

    Asaka, Masahiro; Mabe, Katsuhiro; Matsushima, Rumiko; Tsuda, Momoko

    2015-09-01

    Helicobacter pylori eradication therapy for chronic gastritis achieved world-first coverage by the Japanese national health insurance scheme in 2013, making a dramatic decrease of gastric cancer-related deaths more realistic. Combining H pylori eradication therapy with endoscopic surveillance can prevent the development of gastric cancer. Even if it develops, most patients are likely to be diagnosed at an early stage, possibly resulting in fewer gastric cancer deaths. Success with the elimination of gastric cancer in Japan could lead other countries with a high incidence to consider a similar strategy, suggesting the potential for elimination of gastric cancer around the world.

  15. Basis of decreased risk of gastric cancer in severe atrophic gastritis with eradication of Helicobacter pylori.

    PubMed

    Tari, Akira; Kitadai, Yasuhiko; Sumii, Masaharu; Sasaki, Atsunori; Tani, Hiroshi; Tanaka, Sinji; Chayama, Kazuaki

    2007-01-01

    Helicobacter pylori infection induces chronic gastritis and lowers gastric juice ascorbic acid concentrations. We investigated how H. pylori eradication affected multiple variables that could prevent or delay development of new or occult gastric cancer in patients with early gastric cancer treated by endoscopic mucosal resection. Gastric juice pH, nitrite concentrations, and total vitamin C concentrations, serum concentrations of vitamin C and specific H. pylori antibody, and intensity of neutrophil infiltration in gastric mucosa were determined before and after successful H. pylori eradication. Successful eradication increased acid output and ascorbic acid secretion into gastric juice, accompanied by disappearance of polymorphonuclear infiltration from the surface epithelium and decreased gastric juice nitrite concentrations. Our data suggest that H. pylori eradication decreases the nitrosation rate as the ratio of vitamin C to nitrite increases. This decreases reactive oxygen species and nitric oxide, eliminating their damaging effect on DNA and reducing cell turnover. PMID:17151803

  16. Basis of decreased risk of gastric cancer in severe atrophic gastritis with eradication of Helicobacter pylori.

    PubMed

    Tari, Akira; Kitadai, Yasuhiko; Sumii, Masaharu; Sasaki, Atsunori; Tani, Hiroshi; Tanaka, Sinji; Chayama, Kazuaki

    2007-01-01

    Helicobacter pylori infection induces chronic gastritis and lowers gastric juice ascorbic acid concentrations. We investigated how H. pylori eradication affected multiple variables that could prevent or delay development of new or occult gastric cancer in patients with early gastric cancer treated by endoscopic mucosal resection. Gastric juice pH, nitrite concentrations, and total vitamin C concentrations, serum concentrations of vitamin C and specific H. pylori antibody, and intensity of neutrophil infiltration in gastric mucosa were determined before and after successful H. pylori eradication. Successful eradication increased acid output and ascorbic acid secretion into gastric juice, accompanied by disappearance of polymorphonuclear infiltration from the surface epithelium and decreased gastric juice nitrite concentrations. Our data suggest that H. pylori eradication decreases the nitrosation rate as the ratio of vitamin C to nitrite increases. This decreases reactive oxygen species and nitric oxide, eliminating their damaging effect on DNA and reducing cell turnover.

  17. Function-preserving gastrectomy for gastric cancer in Japan.

    PubMed

    Nomura, Eiji; Okajima, Kunio

    2016-07-14

    Surgery used to be the only therapy for gastric cancer, and since its ability to cure gastric cancer was the focus of attention, less attention was paid to function-preserving surgery in gastric cancer, though it was studied for gastroduodenal ulcer. Maki et al developed pylorus-preserving gastrectomy for gastric ulcer in 1967. At the same time, the definition of early gastric cancer (EGC) was being considered, histopathological investigations of EGC were carried out, and the validity of modified surgery was sustained. After the development of H2-blockers, the number of operations for gastroduodenal ulcers decreased, and the number of EGC patients increased simultaneously. As a result, the indications for pylorus-preserving gastrectomy for EGC in the middle third of the stomach extended, and various alterations were added. Since then, many kinds of function-preserving gastrectomies have been performed and studied in other fields of gastric cancer, and proximal gastrectomy, jejunal pouch interposition, segmental gastrectomy, and local resection have been performed. On the other hand, from the overall perspective, it can be said that endoscopic resection, which was launched at almost the same time, is the ultimate function-preserving surgery under the current circumstances. The current function-preserving gastrectomies that are often performed and studied are pylorus-preserving gastrectomy and proximal gastrectomy. The reasons for this are that these procedures that can be performed with systemic lymph node dissection, and they include three important elements: (1) reduction of the extent of gastrectomy; (2) preservation of the pylorus; and (3) preservation of the vagal nerve. In addition, these operations are more likely to be performed with a laparoscopic approach as minimally invasive surgery. Of the above-mentioned three elements, reduction of the extent of gastrectomy is the most important in our view. Therefore, we should try to reduce the extent of gastrectomy

  18. Function-preserving gastrectomy for gastric cancer in Japan

    PubMed Central

    Nomura, Eiji; Okajima, Kunio

    2016-01-01

    Surgery used to be the only therapy for gastric cancer, and since its ability to cure gastric cancer was the focus of attention, less attention was paid to function-preserving surgery in gastric cancer, though it was studied for gastroduodenal ulcer. Maki et al developed pylorus-preserving gastrectomy for gastric ulcer in 1967. At the same time, the definition of early gastric cancer (EGC) was being considered, histopathological investigations of EGC were carried out, and the validity of modified surgery was sustained. After the development of H2-blockers, the number of operations for gastroduodenal ulcers decreased, and the number of EGC patients increased simultaneously. As a result, the indications for pylorus-preserving gastrectomy for EGC in the middle third of the stomach extended, and various alterations were added. Since then, many kinds of function-preserving gastrectomies have been performed and studied in other fields of gastric cancer, and proximal gastrectomy, jejunal pouch interposition, segmental gastrectomy, and local resection have been performed. On the other hand, from the overall perspective, it can be said that endoscopic resection, which was launched at almost the same time, is the ultimate function-preserving surgery under the current circumstances. The current function-preserving gastrectomies that are often performed and studied are pylorus-preserving gastrectomy and proximal gastrectomy. The reasons for this are that these procedures that can be performed with systemic lymph node dissection, and they include three important elements: (1) reduction of the extent of gastrectomy; (2) preservation of the pylorus; and (3) preservation of the vagal nerve. In addition, these operations are more likely to be performed with a laparoscopic approach as minimally invasive surgery. Of the above-mentioned three elements, reduction of the extent of gastrectomy is the most important in our view. Therefore, we should try to reduce the extent of gastrectomy

  19. Variation in Gene Expression Patterns in Human Gastric Cancers

    PubMed Central

    Chen, Xin; Leung, Suet Y.; Yuen, Siu T.; Chu, Kent-Man; Ji, Jiafu; Li, Rui; Chan, Annie S.Y.; Law, Simon; Troyanskaya, Olga G.; Wong, John; So, Samuel; Botstein, David; Brown, Patrick O.

    2003-01-01

    Gastric cancer is the world's second most common cause of cancer death. We analyzed gene expression patterns in 90 primary gastric cancers, 14 metastatic gastric cancers, and 22 nonneoplastic gastric tissues, using cDNA microarrays representing ∼30,300 genes. Gastric cancers were distinguished from nonneoplastic gastric tissues by characteristic differences in their gene expression patterns. We found a diversity of gene expression patterns in gastric cancer, reflecting variation in intrinsic properties of tumor and normal cells and variation in the cellular composition of these complex tissues. We identified several genes whose expression levels were significantly correlated with patient survival. The variations in gene expression patterns among cancers in different patients suggest differences in pathogenetic pathways and potential therapeutic strategies. PMID:12925757

  20. Glucose metabolism in gastric cancer: The cutting-edge

    PubMed Central

    Yuan, Lian-Wen; Yamashita, Hiroharu; Seto, Yasuyuki

    2016-01-01

    Glucose metabolism in gastric cancer cells differs from that of normal epithelial cells. Upregulated aerobic glycolysis (Warburg effect) in gastric cancer meeting the demands of cell proliferation is associated with genetic mutations, epigenetic modification and proteomic alteration. Understanding the mechanisms of aerobic glycolysis may contribute to our knowledge of gastric carcinogenesis. Metabolomic studies offer novel, convenient and practical tools in the search for new biomarkers for early detection, diagnosis, prognosis, and chemosensitivity prediction of gastric cancer. Interfering with the process of glycolysis in cancer cells may provide a new and promising therapeutic strategy for gastric cancer. In this article, we present a brief review of recent studies of glucose metabolism in gastric cancer, with primary focus on the clinical applications of new biomarkers and their potential therapeutic role in gastric cancer. PMID:26877609

  1. Intake of Soy Products and Other Foods and Gastric Cancer Risk: A Prospective Study

    PubMed Central

    Ko, Kwang-Pil; Park, Sue K.; Yang, Jae Jeong; Ma, Seung Hyun; Gwack, Jin; Shin, Aesun; Kim, YeonJu; Kang, Daehee; Chang, Soung-Hoon; Shin, Hai-Rim; Yoo, Keun-Young

    2013-01-01

    Background Gastric cancer, the most common cancer in the world, is affected by some foods or food groups. We examined the relationship between dietary intake and stomach cancer risk in the Korean Multi-Center Cancer Cohort (KMCC). Methods The KMCC included 19 688 Korean men and women who were enrolled from 1993 to 2004. Of those subjects, 9724 completed a brief 14-food frequency questionnaire at baseline. Through record linkage with the Korean Central Cancer Registry and National Death Certificate databases, we documented 166 gastric cancer cases as of December 31, 2008. Cox proportional hazard models were used to estimate relative risks (RRs) and 95% CIs. Results Frequent intake of soybean/tofu was significantly associated with reduced risk of gastric cancer, after adjustment for age, sex, cigarette smoking, body mass index, alcohol consumption, and area of residence (P for trend = 0.036). We found a significant inverse association between soybean/tofu intake and gastric cancer risk among women (RR = 0.41, 95% CI: 0.22–0.78). Men with a high soybean/tofu intake had a lower risk of gastric cancer, but the reduction was not statistically significant (RR = 0.77, 95% CI: 0.52–1.13). There was no interaction between soybean/tofu intake and cigarette smoking in relation to gastric cancer risk (P for interaction = 0.268). Conclusions Frequent soybean/tofu intake was associated with lower risk of gastric cancer. PMID:23812102

  2. Microarray analysis in gastric cancer: A review

    PubMed Central

    D’Angelo, Giovanna; Di Rienzo, Teresa; Ojetti, Veronica

    2014-01-01

    Gastric cancer is one of the most common tumors worldwide. Although several treatment options have been developed, the mortality rate is increasing. Lymph node involvement is considered the most reliable prognostic indicator in gastric cancer. Early diagnosis improves the survival rate of patients and increases the likelihood of successful treatment. The most reliable diagnostic method is endoscopic examination, however, it is expensive and not feasible in poorer countries. Therefore, many innovative techniques have been studied to develop a new non-invasive screening test and to identify specific serum biomarkers. DNA microarray analysis is one of the new technologies able to measure the expression levels of a large number of genes simultaneously. It is possible to define the gene expression profile of the tumor and to correlate it with the prognosis and metastasis formation. Several studies in the literature have been published on the role of microarray analysis in gastric cancer and the mechanisms of proliferation and metastasis formation. The aim of this review is to analyze the importance of microarray analysis and its clinical applications to better define the genetic characteristics of gastric cancer and its possible implications in a more decisive treatment. PMID:25232233

  3. NCI International EBV-Gastric Cancer Consortium

    Cancer.gov

    A collaboration among NCI and extramural investigators, established by DCEG in 2006, that utilizes data and biospecimens from completed and ongoing case series and observational studies of gastric cancer to replicate and extend findings from previous studies hindered by small numbers of EBV-positive cases, and to stimulate multidisciplinary research in this area.

  4. Galectin-7 is epigenetically-regulated tumor suppressor in gastric cancer

    PubMed Central

    Kim, Seok-Jun; Hwang, Jung-Ah; Ro, Jae Y.; Lee, Yeon-Su; Chun, Kyung-Hee

    2013-01-01

    Gastric cancer is the second leading cause of cancer death and remains a major clinical challenge due to poor prognosis and limited treatment options. Therefore, the basic mechanisms underlying gastric tumorigenesis deserve investigation. Although regulation of the galactoside-binding lectin galectin-7 in cancer has been studied, its role in tumor formation and progression remains controversial. In this study, we investigated galectin-7 expression and its role in gastric cancer. Immunohistochemical staining using a tissue microarray of gastric cancer patients revealed significantly low expression levels of galectin-7 in malignant tissues compared with matched normal tissues, and decreased expression of galectin-7 in malignant tissues was associated with advanced TMN stage disease (p =0.034). Importantly, low expression of galectin-7 in normal tissues was associated with a poor survival rate (p =0.0561). Over-expression of galectin-7 in AGS gastric adenocarcinoma cells suppressed cell proliferation, migration, and invasion, whereas ablation of galectin-7 in KATO III gastric carcinoma cells reversed these properties. AGS cells that overexpressed galectin-7 could not form gastric tumors in xenografted mice. More than 70% hypermethylation was observed in 7 of 9 gastric cancer cell lines tested and 5-aza-cytidine treatment lowered galectin-7 expression by reducing methylation in 24 cancer cell lines from five different organ origins. We analyzed CpG islands in the galectin-7 genomic region and detected hypermethylation at +1566bp of exon 2, the predicted p53 binding region. DNA hypermethylation of this region was also detected in gastric cancer tissues from 20 patients. Taken together, our data indicate that galectin-7 has a tumor suppressive function, and that the gene is epigenetically modified by DNA methylation and significantly down-regulated in gastric cancer. Further study of galectin-7 regulation may lead to improved gastric cancer diagnosis and therapy. PMID

  5. Dietary Flavonoids and Gastric Cancer Risk in a Korean Population

    PubMed Central

    Woo, Hae Dong; Lee, Jeonghee; Choi, Il Ju; Kim, Chan Gyoo; Lee, Jong Yeul; Kwon, Oran; Kim, Jeongseon

    2014-01-01

    Gastric cancer is the most common cancer among men in Korea, and dietary factors are closely associated with gastric cancer risk. We performed a case-control study using 334 cases and 334 matched controls aged 35–75 years. Significant associations were observed in total dietary flavonoids and their subclasses, with the exception of anthocyanidins and isoflavones (OR (95% CI): 0.49 (0.31–0.76), p trend = 0.007 for total flavonoids). However, these associations were not significant after further adjustment for fruits and vegetable consumption (OR (95% CI): 0.62 (0.36–1.09), p trend = 0.458 for total flavonoids). Total flavonoids and their subclasses, except for isoflavones, were significantly associated with a reduced risk gastric cancer in women (OR (95% CI): 0.33 (0.15–0.73), p trend = 0.001 for total flavonoids) but not in men (OR (95% CI): 0.70 (0.39–1.24), p trend = 0.393 for total flavonoids). A significant inverse association with gastric cancer risk was observed in flavones, even after additional adjustment for fruits and vegetable consumption in women. No significantly different effects of flavonoids were observed between H. pylori-positive and negative subjects. In conclusion, dietary flavonoids were inversely associated with gastric cancer risk, and these protective effects of dietary flavonoids were prominent in women. No clear differences were observed in the subgroup analysis of H. pylori and smoking status. PMID:25389898

  6. Current status in remnant gastric cancer after distal gastrectomy

    PubMed Central

    Ohira, Masaichi; Toyokawa, Takahiro; Sakurai, Katsunobu; Kubo, Naoshi; Tanaka, Hiroaki; Muguruma, Kazuya; Yashiro, Masakazu; Onoda, Naoyoshi; Hirakawa, Kosei

    2016-01-01

    Remnant gastric cancer (RGC) and gastric stump cancer after distal gastrectomy (DG) are recognized as the same clinical entity. In this review, the current knowledges as well as the non-settled issues of RGC are presented. Duodenogastric reflux and denervation of the gastric mucosa are considered as the two main factors responsible for the development of RGC after benign disease. On the other hand, some precancerous circumstances which already have existed at the time of initial surgery, such as atrophic gastritis and intestinal metaplasia, are the main factors associated with RGC after gastric cancer. Although eradication of Helicobacter pylori (H. pylori) in remnant stomach is promising, it is still uncertain whether it can reduce the risk of carcinogenesis. Periodic endoscopic surveillance after DG was reported useful in detecting RGC at an early stage, which offers a chance to undergo minimally invasive endoscopic treatment or laparoscopic surgery and leads to an improved prognosis in RGC patients. Future challenges may be expected to elucidate the benefit of eradication of H. pylori in the remnant stomach if it could reduce the risk for RGC, to build an optimal endoscopic surveillance strategy after DG by stratifying the risk for development of RGC, and to develop a specific staging system for RGC for the standardization of the treatment by prospecting the prognosis. PMID:26937131

  7. Effects of IL-10 haplotype and atomic bomb radiation exposure on gastric cancer risk.

    PubMed

    Hayashi, Tomonori; Ito, Reiko; Cologne, John; Maki, Mayumi; Morishita, Yukari; Nagamura, Hiroko; Sasaki, Keiko; Hayashi, Ikue; Imai, Kazue; Yoshida, Kengo; Kajimura, Junko; Kyoizumi, Seishi; Kusunoki, Yoichiro; Ohishi, Waka; Fujiwara, Saeko; Akahoshi, Masazumi; Nakachi, Kei

    2013-07-01

    Gastric cancer (GC) is one of the cancers that reveal increased risk of mortality and incidence in atomic bomb survivors. The incidence of gastric cancer in the Life Span Study cohort of the Radiation Effects Research Foundation (RERF) increased with radiation dose (gender-averaged excess relative risk per Gy = 0.28) and remains high more than 65 years after exposure. To assess a possible role of gene-environment interaction, we examined the dose response for gastric cancer incidence based on immunosuppression-related IL-10 genotype, in a cohort study with 200 cancer cases (93 intestinal, 96 diffuse and 11 other types) among 4,690 atomic bomb survivors participating in an immunological substudy. Using a single haplotype block composed of four haplotype-tagging SNPs (comprising the major haplotype allele IL-10-ATTA and the minor haplotype allele IL-10-GGCG, which are categorized by IL-10 polymorphisms at -819A>G and -592T>G, +1177T>C and +1589A>G), multiplicative and additive models for joint effects of radiation and this IL-10 haplotyping were examined. The IL-10 minor haplotype allele(s) was a risk factor for intestinal type gastric cancer but not for diffuse type gastric cancer. Radiation was not associated with intestinal type gastric cancer. In diffuse type gastric cancer, the haplotype-specific excess relative risk (ERR) for radiation was statistically significant only in the major homozygote category of IL-10 (ERR = 0.46/Gy, P = 0.037), whereas estimated ERR for radiation with the minor IL-10 homozygotes was close to 0 and nonsignificant. Thus, the minor IL-10 haplotype might act to reduce the radiation related risk of diffuse-type gastric cancer. The results suggest that this IL-10 haplotyping might be involved in development of radiation-associated gastric cancer of the diffuse type, and that IL-10 haplotypes may explain individual differences in the radiation-related risk of gastric cancer.

  8. [Matrix metalloproteases as molecular markers in gastric cancer].

    PubMed

    de la Peña, Sol; Sampieri, Clara L; León-Córdoba, Kenneth

    2010-02-01

    Gastric cancer is the second leading cause of cancer-associated mortality in the world. Prognosis in patients with gastric cancer is difficult to establish because it is commonly diagnosed when gastric wall invasion and metastasis have occurred. Currently, some members of the extracellular matrix metalloproteinases have been identified, whose expression in gastric tumor tissue is significantly elevated compared to healthy gastric tissue. Matrix metalloproteinases are 24 zinc-dependent endopeptidases that catalyze the proteolysis of the extracellular matrix. This degradation allows the cancer cells invade the surrounding stroma and trigger metastasis. Upregulation of certain matrix metalloproteinases in gastric cancer has been associated with a poor prognosis and elevated invasive capacity. This review compiles evidence about the genetic expression of matrix metalloproteinases in gastric cancer and their role in tumour invasion and metastasis, emphasizing their potential as molecular markers of prognosis.

  9. Gastric Cancer Screening in Korea: Report on the National Cancer Screening Program in 2008

    PubMed Central

    Lee, Kyung Sook; Oh, Dong Kwan; Han, Mi Ah; Lee, Hoo-Yeon; Choi, Kui Son; Park, Eun-Cheol

    2011-01-01

    Purpose The National Cancer Screening Program (NCSP) began in 1999. The objective of this report is to evaluate the results of the NCSP in 2008 and provide essential evidence associated with the gastric cancer screening program in Korea. Materials and Methods Data was obtained from the National Cancer Screening Information System; participation rates in gastric cancer screening were calculated. According to screening modalities, recall rates were estimated with 95% confidence intervals (CIs). Results The target population of the gastric cancer screening program in 2008 was 7,132,820 Korean men and women aged 40 and over, 2,076,544 of whom underwent upper endoscopy or upper gastrointestinal (UGI) series as screening tools (participation rate, 29.1%). Disparities in participation rates were observed relating to gender and health insurance type. Overall, recall rates of upper endoscopy and UGI series were 3.1% (95% CI, 3.0 to 3.1) and 33.3% (95% CI, 33.3 to 33.4), respectively. Conclusion According to our research, efforts to facilitate participation and to reduce disparities in gastric cancer screening among Korean men and women are needed. These results will provide essential data for evidence-based strategies in gastric cancer control in Korea. PMID:21811423

  10. Sensitive and Specific Detection of Early Gastric Cancer Using DNA Methylation Analysis of Gastric Washes

    PubMed Central

    Watanabe, Yoshiyuki; Kim, Hyun Soo; Castoro, Ryan J.; Chung, Woonbok; Estecio, Marcos R. H.; Kondo, Kimie; Guo, Yi; Ahmed, Saira S.; Toyota, Minoru; Itoh, Fumio; Suk, Ki Tae; Cho, Mee-Yon; Shen, Lanlan; Jelinek, Jaroslav; Issa, Jean-Pierre J.

    2009-01-01

    Background & Aims Aberrant DNA methylation is an early and frequent process in gastric carcinogenesis and could be useful for detection of gastric neoplasia. We hypothesized that methylation analysis of DNA recovered from gastric washes could be used to detect gastric cancer. Methods We studied 51 candidate genes in 7 gastric cancer cell lines and 24 samples (training set) and identified 6 for further studies. We examined the methylation status of these genes in a test set consisting of 131 gastric neoplasias at various stages. Finally, we validated the 6 candidate genes in a different population of 40 primary gastric cancer samples and 113 non-neoplastic gastric mucosa samples. Results 6 genes (MINT25, RORA, GDNF, ADAM23, PRDM5, MLF1) showed frequent differential methylation between gastric cancer and normal mucosa in the training, test and validation sets. GDNF and MINT25 were most sensitive molecular markers of early stage gastric cancer while PRDM5 and MLF1 were markers of a field defect. There was a close correlation (r=0.5 to 0.9, p=0.03 to 0.001) between methylation levels in tumor biopsy and gastric washes. MINT25 methylation had the best sensitivity (90%), specificity (96%), and area under the ROC curve (0.961) in terms of tumor detection in gastric washes. Conclusions These findings suggest MINT25 is a sensitive and specific marker for screening in gastric cancer. Additionally we have developed a new methodology for gastric cancer detection by DNA methylation in gastric washes. PMID:19375421

  11. HER2 testing in gastric cancer.

    PubMed

    Albarello, Luca; Pecciarini, Lorenza; Doglioni, Claudio

    2011-01-01

    Molecular therapies targeting HER2 are part of the established drug armamentarium in breast carcinoma. Now the ToGA trial, an international multicenter phase III clinical study, involving 24 countries globally, has shown that the anti-HER2 humanized monoclonal antibody Trastuzumab is effective in prolonging survival in HER2-positive carcinoma of the stomach and the gastroesophageal junction (GEJ). Similarly to breast carcinoma, >20% of gastric cancers show HER2 overexpression and/or amplification, and this percentage increases to 33% in GEJ tumors. Thus, as in breast carcinoma, pathologists are now asked to evaluate HER2 status in gastric carcinoma samples. As validated in the ToGA trial, the HER2 testing criteria that must be used in evaluating both gastric carcinoma biopsies and surgical specimens significantly differ from those routinely applied in breast carcinoma. The main variations with regard to the pattern of reactivity in HER2-expressing cells are as follows: the completeness of membrane staining is not a "conditio sine qua non" and the number of stained cells necessary to consider a case as positive is different. We must also take note of the much more frequent heterogeneity of HER2 positivity in gastric cancer compared with breast carcinoma and the less stringent correlation between HER2 amplification and protein overexpression that is observed in gastric carcinoma, where more than 20% of cases may carry HER2 amplification, although of low level, without HER2 expression. In these patients, in the ToGA trial, there was no apparent benefit from adding Trastuzumab to chemotherapy: for this reason the European Medicines Agency, while approving usage of Trastuzumab for metastatic adenocarcinoma treatment, indicated HER2 testing by immunohistochemistry as first evaluation assay, followed by fluorescence in situ hybridization in 2+ equivocal cases. HER2 testing in gastric carcinoma is a new field, opening several opportunities: for patients with gastric cancer

  12. Risk Factors and Epidemiology of Gastric Cancer in Pakistan.

    PubMed

    Daniyal, Muhammad; Ahmad, Saeed; Ahmad, Mukhtiar; Asif, Hafiz Muhammad; Akram, Muhammad; Ur Rehman, Saif; Sultana, Sabira

    2015-01-01

    Gastric cancer is the 2nd most common cause of death among all cancers and is the 4th most common cancer in the world. The number of deaths due to gastric cancer is about 800,000 annually. Gastric cancer is more common in men as compared to women and is 3rd most common cancer after colorectal and breast cancers in women. A progressive rise in the incidence rate has been observed in females over the last 5 years. The highest incidence of stomach cancer is in China, South America and Eastern Europe. The incidence of gastric cancer has 20 fold variation worldwide. Global variation is linked by two factors which play important role in developing gastric cancer. One is infection with Helicobacter pylori and the 2nd is diet. South Asia is a region with low risk, despite a high prevalence of H.pylori. Gastric carcinoma is common in southern region of India. Gastric cancer is more readily treated if diagnosed early. This study aims to provide awareness about gastric cancer as well as an updated knowledge about risk factors and epidemiology of gastric cancer in Pakistan.

  13. PIVKA-II-producing advanced gastric cancer.

    PubMed

    Takano, Shigetsugu; Honda, Ichiro; Watanabe, Satoshi; Soda, Hiroaki; Nagata, Matsuo; Hoshino, Isamu; Takenouchi, Toshinao; Miyazaki, Masaru

    2004-08-01

    We describe the case of a 68-year-old man with primary advanced adenocarcinoma of the stomach, who displayed extremely high plasma levels of protein induced by vitamin K antagonist (PIVKA)-II (15 600 mAU/ml) and normal levels of alphafetoprotein (AFP) (4 ng/ml). Ultrasonography and dynamic computed tomography ruled out hepatocellular carcinoma (HCC) or liver metastasis. After preoperative chemotherapy, pancreatico-spleno total gastrectomy with D2 lymphadenectomy was performed. Postoperatively, plasma levels of PIVKA-II returned to within the normal range (29 mAU/ml). Microscopic examination revealed stomach adenocarcinoma showing various histological types, such as moderately to poorly differentiated mucinous adenocarcinoma, but hepatoid differentiation of gastric adenocarcinoma was not detected. Localization of PIVKA-II and AFP within tumor cells was demonstrated by immunohistochemical staining using monoclonal antibodies. These results indicate that tumor cells from gastric cancer may produce PIVKA-II. Some cases of PIVKA-II- and AFP-producing advanced gastric cancer with liver metastasis have been reported, but this is the first report of gastric cancer without liver metastasis producing PIVKA-II alone.

  14. Adipokines and ghrelin in gastric cancer cachexia

    PubMed Central

    Kerem, Mustafa; Ferahkose, Zafer; Yilmaz, Utku Tonguc; Pasaoglu, Hatice; Ofluoglu, Ebru; Bedirli, Abdulkadir; Salman, Bulent; Sahin, Tevfik Tolga; Akin, Murat

    2008-01-01

    AIM: To investigate the roles of the adipocytokines, ghrelin and leptin in gastric cancer cachexia. METHODS: Resistin, ghrelin, leptin, adiponectin, insulin and insulin-like growth factor (IGF-I), were measured in 30 healthy subjects, and 60 gastric cancer patients of which 30 suffered from cancer-induced cachexia and 30 served as a control group. The relationships between hormones, body mass index (BMI) loss ratio, age, gender, and Glasgow Prognostic Score (GPS) were investigated. RESULTS: Cachexia patients had higher tumor stage and GPS when compared with non-cachexia patients (P < 0.05). Ghrelin, resistin, leptin, adiponectin and IGF-I, showed a significant correlation with BMI loss ratio and GPS (P < 0.05). A strong correlation was seen between GPS and BMI loss (R = -0.570, P < 0.0001). Multivariate analysis indicated that BMI loss was significantly independent as a predictor of ghrelin, resistin, leptin and IGF-I (P < 0.05). Existence of an important significant relationship between resistin and insulin resistance was also noted. CONCLUSION: These results showed that serum ghrelin, leptin, adiponectin, and IGF-I play important roles in cachexia-related gastric cancers. No relationship was found between resistin and cancer cachexia. Also, because of the correlation between these parameters and GPS, these parameters might be used as a predictor factor. PMID:18595130

  15. Early Gastric Cancer Just above a Heterotopic Pancreas

    PubMed Central

    Murabayashi, Toji; Kawaguchi, Shinya; Okuda, Naoko; Oyamada, Jun; Yabana, Tadashi

    2016-01-01

    We report the first case of early gastric cancer just above a heterotopic pancreas for which the differential diagnosis was carcinoma arising from heterotopic pancreas. Routine upper gastrointestinal endoscopy in an 83-year-old man with sigmoid colon cancer revealed a gastric cancer in the lesser curvature of the antrum. Endoscopic ultrasonography (EUS) for evaluating the depth of tumor invasion revealed a hypoechoic mass in the submucosal layer. The depth of tumor invasion was diagnosed as muscularis propria. Distal gastrectomy and sigmoidectomy were performed. Histologically, the resected specimen of the stomach unexpectedly revealed a heterotopic pancreas just below the gastric cancer. They were not linked, and the heterotopic pancreas had no dysplasia. The gastric cancer had slightly invaded the submucosa. The hypoechoic mass on EUS was not the invasive tumor but the heterotopic pancreas. The preoperative staging of the gastric cancer on EUS was confounded by the presence of the heterotopic pancreas just below the gastric cancer. PMID:27482189

  16. Gastric cancer-molecular and clinical dimensions.

    PubMed

    Wadhwa, Roopma; Song, Shumei; Lee, Ju-Seog; Yao, Yixin; Wei, Qingyi; Ajani, Jaffer A

    2013-11-01

    Gastric cancer imposes a considerable health burden around the globe despite its declining incidence. The disease is often diagnosed in advanced stages and is associated with a poor prognosis for patients. An in-depth understanding of the molecular underpinnings of gastric cancer has lagged behind many other cancers of similar incidence and morbidity, owing to our limited knowledge of germline susceptibility traits for risk and somatic drivers of progression (to identify novel therapeutic targets). A few germline (PLCE1) and somatic (ERBB2, ERBB3, PTEN, PI3K/AKT/mTOR, FGF, TP53, CDH1 and MET) alterations are emerging and some are being pursued clinically. Novel somatic gene targets (ARID1A, FAT4, MLL and KMT2C) have also been identified and are of interest. Variations in the therapeutic approaches dependent on geographical region are evident for localized gastric cancer-differences that are driven by preferences for the adjuvant strategies and the extent of surgery coupled with philosophical divides. However, greater uniformity in approach has been noted in the metastatic cancer setting, an incurable condition. Having realized only modest successes, momentum is building for carrying out more phase III comparative trials, with some using biomarker-based patient selection strategies. Overall, rapid progress in biotechnology is improving our molecular understanding and can help with new drug discovery. The future prospects are excellent for defining biomarker-based subsets of patients and application of specific therapeutics. However, many challenges remain to be tackled. Here, we review representative molecular and clinical dimensions of gastric cancer.

  17. [Mechanisms responsible for the progression of scirrhous gastric cancer].

    PubMed

    Yashiro, Masakazu; Ohira, Masaichi; Muguruma, Kazuya; Shinto, Osamu; Hirakawa, Kosei

    2012-10-01

    Scirrhous gastric carcinoma is characterized by rapid cancer cell infiltration and proliferation accompanied by extensive stromal fibrosis. The proliferative and invasive ability of scirrhous gastric cancer cells are closely associated with the growth factors, FGF7 and TGFbeta produced by organ-specific fibroblasts. Peritoneal fibroblasts morphologically change mesothelial cells, and stimulate the migratory capability of cancer cells. A FGFR2 phosphorylation inhibitor prolongs the survival of mice with peritoneal metastasis of scirrhous gastric cancer. A TGFbetaR inhibitor decreases the growth of fibroblast, and invasion-stimulating activity of fibroblasts on cancer cells. A FGFR2 phosphorylation inhibitor or TGFbetaR inhibitor appears therapeutically promising in scirrhous gastric carcinoma.

  18. Helicobacter pylori infection in relation to gastric cancer progression.

    PubMed

    Venkateshwari, A; Krishnaveni, D; Venugopal, S; Shashikumar, P; Vidyasagar, A; Jyothy, A

    2011-01-01

    Gastric cancer is a major cause of cancer death worldwide, especially in developing countries. The incidence of gastric cancer varies from country to country, probably as a result of genetic, epigenetic, and environmental factors. H. pylori infection is considered as a major risk factor in the development of gastric cancer. However, the scenario varies in Asian countries, exhibiting a higher rate of H. pylori infection and low incidence of gastric cancer, which could be attributed to strain-specific virulence factors and host genetic makeup. In this review, we discuss the various virulence factors expressed by this bacterium and their interaction with the host factors, to influence pathogenesis. PMID:21248438

  19. Prognostic significance of aberrant gene methylation in gastric cancer.

    PubMed

    Shi, Jing; Zhang, Guanjun; Yao, Demao; Liu, Wei; Wang, Na; Ji, Meiju; He, Nongyue; Shi, Bingyin; Hou, Peng

    2012-01-01

    Promoter methylation acts as an important alternative to genetic alterations for gene inactivation in gastric carcinogenesis. Although a number of gastric cancer-associated genes have been found to be methylated in gastric cancer, valuable methylation markers for early diagnosis and prognostic evaluation of this cancer remain largely unknown. In the present study, we used methylation-specific PCR (MSP) to analyze promoter methylation of 9 gastric cancer-associated genes, including MLF1, MGMT, p16, RASSF2, hMLH1, HAND1, HRASLS, TM, and FLNc, and their association with clinicopathological characteristics and clinical outcome in a large cohort of gastric cancers. Our data showed that all of these genes were aberrantly methylated in gastric cancer, ranging from 8% to 51%. Moreover, gene methylation was strongly associated with certain clinicopathological characteristics, such as tumor differentiation, lymph node metastasis, and cancer-related death. Of interest, methylation of MGMT, p16, RASSF2, hMLH1, HAND1, and FLNc was closely associated with poor survival in gastric cancer, particularly MGMT, p16, RASSF2 and FLNc. Thus, our findings suggested these epigenetic events may contribute to the initiation and progression of gastric cancer. Importantly, methylation of some genes were closely relevant to poor prognosis in gastric cancer, providing the strong evidences that these hypermethylated genes may be served as valuable biomarkers for prognostic evaluation in this cancer.

  20. KDM5B is overexpressed in gastric cancer and is required for gastric cancer cell proliferation and metastasis

    PubMed Central

    Wang, Zhenran; Tang, Fang; Qi, Guangying; Yuan, Shengguang; Zhang, Guangyu; Tang, Bo; He, Songqing

    2015-01-01

    Epigenetic alterations such as aberrant expression of histone-modifying enzymes have been implicated in tumorigenesis. KDM5B (also known as JARID1B) is a newly identified histone demethylase that regulates chromatin structure or gene expression by removing methyl residues from trimethylated lysine 4 on histone H3. Recent observations have shown oncogenic activity of KDM5B. However, the role of KDM5B in gastric cancer carcinogenesis remains unclear. In this study, we aimed to investigate the role of KDM5B in gastric cancer. Immunohistochemical analysis, western blotting, and qRT-PCR were used to measure the levels of KDM5B in gastric cancer cell lines, 45 pairs of gastric cancer tissues and the adjacent nonneoplastic tissues. KDM5B and shKDM5B were transfected into gastric cancer cells to investigate its role on regulating cell proliferation which was measured by MTT and colony formation assay. Cell’s migration and invasion were measured by Transwell and Matrigel analysis in vitro. PCNA expression was measured by immunofluorescence staining and immunohistochemical analysis. The in vivo tumorigenesis and metastasis assays were performed in SCID mice. In clinical gastric cancer samples, we found that KDM5B expression was significantly up-regulated in cancer lesions compared with paired normal gastric tissues. By silencing or overexpressing KDM5B in gastric cancer cells, we found that KDM5B could promote cell growth and metastasis in vitro. An in vivo assay showed that KDM5B not only dramatically promoted gastric cancer cell xenograft formation and growth but also promoted gastric cancer cell metastasis in a liver metastasis model. Moreover, we demonstrated that KDM5B promoted gastric cancer metastasis via regulation of the Akt pathway. Our study provided evidence that KDM5B functions as a novel tumor oncogene in gastric cancer and may be a potential therapeutic target for gastric cancer management. PMID:25628922

  1. Salt processed food and gastric cancer in a Chinese population.

    PubMed

    Lin, Si-Hao; Li, Yuan-Hang; Leung, Kayee; Huang, Cheng-Yu; Wang, Xiao-Rong

    2014-01-01

    To investigate the association between salt processed food and gastric cancer, a hospital based case-control study was conducted in a high risk area of China. One hundred and seven newly diagnosed cases with histological confirmation of gastric cancer and 209 controls were recruited. Information on dietary intake was collected with a validated food frequency questionnaire. Unconditional logistic regression was applied to estimate the odds ratios with adjustment for other potential confounders. Comparing the high intake group with never consumption of salt processed foods, salted meat, pickled vegetables and preserved vegetables were significantly associated with increased risk of gastric cancer. Meanwhile, salt taste preference in diet showed a dose-response relationship with gastric cancer. Our results suggest that consumption of salted meat, pickled and preserved vegetables, are positively associated with gastric cancer. Reduction of salt and salt processed food in diets might be one practical measure to preventing gastric cancer.

  2. Metachronous gastric cancer after successful Helicobacter pylori eradication.

    PubMed

    Shiotani, Akiko; Haruma, Ken; Graham, David Y

    2014-09-01

    The high incidence of gastric cancer in Japan initially resulted in establishment of a country-wide gastric cancer screening program to detect early and treatable cancers. In 2013 countrywide Helicobacter pylori (H. pylori) eradication was approved coupled with endoscopy to assess for the presence of chronic gastritis. Current data support the notion that cure of the infection in those with non-atrophic gastritis will prevent development of gastric cancer. However, while progression to more severe damage is halted in those who have already developed, atrophic gastritis/gastric atrophy remain at risk for subsequent development of gastric cancer. That risk is directly related to the extent and severity of atrophic gastritis. Methods to stratify cancer risk include those based on endoscopic assessment of the atrophic border, histologic grading, and non-invasive methods based on serologic testing of pepsinogen levels. Continued surveillance is required because those with atrophic gastritis/gastric atrophy retain considerable gastric cancer risk even after H. pylori eradication. Those who have already experienced a resectable early gastric cancer are among those at highest risk as metachronous lesions are frequent even after H. pylori eradication. We review the role of H. pylori and effect of H. pylori eradication indicating the incidence and the predictive factors on development of metachronous cancer after endoscopic therapy of early gastric cancer. Studies to refine risk markers to stratify for risk, surveillance methods, intervals, and duration after successful H. pylori eradication, and whether adjuvant therapy would change risk are needed.

  3. Metachronous gastric cancer after successful Helicobacter pylori eradication

    PubMed Central

    Shiotani, Akiko; Haruma, Ken; Graham, David Y

    2014-01-01

    The high incidence of gastric cancer in Japan initially resulted in establishment of a country-wide gastric cancer screening program to detect early and treatable cancers. In 2013 countrywide Helicobacter pylori (H. pylori) eradication was approved coupled with endoscopy to assess for the presence of chronic gastritis. Current data support the notion that cure of the infection in those with non-atrophic gastritis will prevent development of gastric cancer. However, while progression to more severe damage is halted in those who have already developed, atrophic gastritis/gastric atrophy remain at risk for subsequent development of gastric cancer. That risk is directly related to the extent and severity of atrophic gastritis. Methods to stratify cancer risk include those based on endoscopic assessment of the atrophic border, histologic grading, and non-invasive methods based on serologic testing of pepsinogen levels. Continued surveillance is required because those with atrophic gastritis/gastric atrophy retain considerable gastric cancer risk even after H. pylori eradication. Those who have already experienced a resectable early gastric cancer are among those at highest risk as metachronous lesions are frequent even after H. pylori eradication. We review the role of H. pylori and effect of H. pylori eradication indicating the incidence and the predictive factors on development of metachronous cancer after endoscopic therapy of early gastric cancer. Studies to refine risk markers to stratify for risk, surveillance methods, intervals, and duration after successful H. pylori eradication, and whether adjuvant therapy would change risk are needed. PMID:25206262

  4. Gastritis, nitrosamines, and gastric cancer

    SciTech Connect

    Stemmermann, G.N.; Mower, H.

    1981-01-01

    Gastritis is associated with peptic ulcer, gastroenterostomy, pernicious anemia, and exposure to nitrosamines. Once established, the process may be self-perpetuating, resulting in atrophy, metaplasia, dysplasia, and neoplasia. This can be explained by the process of endogenous nitrosation of amines in the inflamed gastric mucosa. Evidence is presented to support this hypothesis. Several drugs given parenterally have been identified as mutagenic nitroso compounds in homogenates of human and canine antral mucosa. Nitrite for this process is apparently derived from the inflamed mucosa. Different amines appear to be nitrosated at different places in the antrum, suggesting the presence of site-specific enzymes that control these reactions.

  5. Pretreatment Gastric Lavage Reduces Postoperative Bleeding after Endoscopic Submucosal Dissection for Gastric Neoplasms

    PubMed Central

    Takahashi, Yuka; Itakura, Jun; Ueda, Ken; Suzuki, Shoko; Yasui, Yutaka; Tamaki, Nobuharu; Nakakuki, Natsuko; Takada, Hitomi; Ueda, Masako; Hayashi, Tsuguru; Kuwabara, Konomi; Takaura, Kenta; Higuchi, Mayu; Komiyama, Yasuyuki; Yoshida, Tsubasa; Izumi, Namiki

    2016-01-01

    Aim For patients receiving endoscopic submucosal dissection (ESD), there is urgent need pertaining to the prevention of postoperative bleeding. We conducted a retrospective propensity score-matched study that evaluated whether pre-ESD gastric lavage prevents postoperative bleeding after ESD for gastric neoplasms. Methods From September 2002 to October 2015, the 760 consecutive patients receiving ESD for gastric neoplasm were enrolled and data regarding them were retrospectively analyzed. All patients received conventional preventive treatment against delayed bleeding after ESD, including the administration of proton pump inhibitor and preventive coagulation of visible vessels, at the end of the ESD procedure. Results Pre-ESD risk factors for postoperative bleeding included tumor size and no gastric lavage. Using multivariate analysis tumor size >2.0 cm (HR 2.90, 95% CI 1.65–5.10, p = 0.0002) and no gastric lavage (HR 3.20, 95% CI 1.13–9.11, p = 0.029) were found to be independent risk factors. Next, we evaluated the effect of gastric lavage on the prevention of post-ESD bleeding using a propensity score-matching method. A total of 284 subjects (142 per group) were selected. Adjusted odds ratio of gastric lavage for post-ESD bleeding was 0.25 (95% CI 0.071–0.886, p = 0.032). Conclusion Pretreatment gastric lavage reduced postoperative bleeding in patients receiving ESD for gastric neoplasm. PMID:26871449

  6. Podocalyxin as a Prognostic Marker in Gastric Cancer

    PubMed Central

    Laitinen, Alli; Böckelman, Camilla; Hagström, Jaana; Kokkola, Arto; Fermér, Christian; Nilsson, Olle; Haglund, Caj

    2015-01-01

    Background Podocalyxin-like 1 (PODXL) is a cell-adhesion glycoprotein associated with aggressive tumor phenotype and poor prognosis in several forms of cancer. The aim of this study was to investigate PODXL expression in gastric cancer by use of two different antibodies. Methods By tumor-tissue microarrays and immunohistochemistry we evaluated PODXL expression in tumor specimens from 337 patients who underwent surgery for gastric adenocarcinoma at Helsinki University Hospital. We used two different antibodies: HPA2110, which is a polyclonal antibody and an in-house monoclonal antibody called HES9, to investigate the association of PODXL expression with clinicopathologic variables and patient survival. Results PODXL staining was positive by the polyclonal antibody in 153 (57.5%) cases and by the monoclonal antibody in 212 (76%). Polyclonal antibody expression was associated with intestinal cancer type (p<0.001). Monoclonal antibody staining was associated with age over 66 (p = 0.001), with intestinal cancer (p<0.001), and with small tumor size (≤ 5 cm; p = 0.024). Both antibodies were associated with high S-phase fraction (p = 0.022; p = 0.010), and high tumor proliferation index (Ki-67; p = 0.003; p = 0.001). PODXL positivity by the polyclonal antibody indicated reduced gastric-cancer-specific 5-year survival of 24.0% (95% CI 16.9–31.1), compared to 43.3% (95% CI 33.7–52.9) for patients with PODXL negativity (p = 0.001). The result remained significant in multivariable analysis (HR = 3.17; 95% CI 1.37–7.34, p = 0.007). Conclusion In gastric cancer, PODXL expression by the polyclonal antibody HPA2110 is an independent marker of poor prognosis. PMID:26674770

  7. Helicobacter pylori infection induced gastric cancer; advance in gastric stem cell research and the remaining challenges

    PubMed Central

    2012-01-01

    Helicobacter pylori infection is the major cause of gastric cancer, which remains an important health care challenge. Recent investigation in gastric stem cell or progenitor cell biology has uncovered valuable information in understanding the gastric gland renewal and maintenance of homeostasis, they also provide clues for further defining the mechanisms by which gastric cancer may originate and progress. Lgr5, Villin-promoter, TFF2-mRNA and Mist have recently been identified as gastric stem/progenitor cell markers; their identification enriched our understanding on the gastric stem cell pathobiology during chronic inflammation and metaplasia. In addition, advance in gastric cancer stem cell markers such as CD44, CD90, CD133, Musashi-1 reveal novel information on tumor cell behavior and disease progression implicated for therapeutics. However, two critical questions remain to be of considerable challenges for future exploration; one is how H. pylori or chronic inflammation affects gastric stem cell or their progenitors, which give rise to mucus-, acid-, pepsinogen-, and hormone-secreting cell lineages. Another one is how bacterial infection or inflammation induces oncogenic transformation and propagates into tumors. Focus on the interactions of H. pylori with gastric stem/progenitor cells and their microenvironment will be instrumental to decipher the initiation and origin of gastric cancer. Future studies in these areas will be critical to uncover molecular mechanisms of chronic inflammation-mediated oncogenic transformation and provide options for cancer prevention and intervention. We review recent progress and discuss future research directions in these important research fields. PMID:23217022

  8. Early cancer of the gastric remnant.

    PubMed Central

    Pointner, R; Schwab, G; Königsrainer, A; Bodner, E; Schmid, K W

    1988-01-01

    Early carcinoma of the gastric remnant was diagnosed in 19 patients between January 1976 and January 1986. In all patients early cancer was suspected at endoscopy and confirmed by biopsy and histology. The main reason for endoscopic examination was diffuse epigastric pain suggestive of stump gastritis. The surgical procedure was stump gastrectomy. Two of the 19 patients were not operated on because of advanced age. In contrast with the poor prognosis of patients with cancers of the gastric remnant of tumour stages T2 to T4 according to the TNM-classification regardless of their NM-stage, patients with tumour stage T1N0 and T1N1 have a good prognosis. PMID:3356360

  9. Gastric cancer research in Mexico: A public health priority

    PubMed Central

    Sampieri, Clara Luz; Mora, Mauricio

    2014-01-01

    This study aimed review studies conducted on Mexican patients diagnosed with gastric cancer and/or diseases associated with its development, in which at least one Mexican institute has participated, and to assess their contributions to the primary and secondary prevention of this disease. A search of the Medline database was conducted using the following keywords: gastric/stomach cancer, Mexico. Studies of the Mexican population were selected in which at least one Mexican Institute had participated and where the findings could support public policy proposals directed towards the primary or secondary prevention of gastric cancer. Of the 148 studies found in the Medline database, 100 were discarded and 48 were reviewed. According to the analysis presented, these studies were classified as: epidemiology of gastric cancer (5/48); risk factors and protectors relating to gastric cancer (9/48); relationship between Helicobacter pylori and pathologies associated with gastric cancer and the development of the disease (16/48); relationship between the Epstein-Barr virus and pathologies associated with gastric cancer and the development of the disease (3/48); molecular markers for the development of diseases associated with gastric cancer and gastric cancer (15/48). Mexico requires a program for the prevention and control of gastric cancer based on national health indicators. This should be produced by a multidisciplinary committee of experts who can propose actions that are relevant in the current national context. The few studies of gastric cancer conducted on the Mexican population in national institutes highlight the poor connection that currently exists between the scientific community and the health sector in terms of resolving this health issue. Public policies for health research should support projects with findings that can be translated into benefits for the population. This review serves to identify national research groups studying gastric cancer in the Mexican

  10. Gastric cancer research in Mexico: a public health priority.

    PubMed

    Sampieri, Clara Luz; Mora, Mauricio

    2014-04-28

    This study aimed review studies conducted on Mexican patients diagnosed with gastric cancer and/or diseases associated with its development, in which at least one Mexican institute has participated, and to assess their contributions to the primary and secondary prevention of this disease. A search of the Medline database was conducted using the following keywords: gastric/stomach cancer, Mexico. Studies of the Mexican population were selected in which at least one Mexican Institute had participated and where the findings could support public policy proposals directed towards the primary or secondary prevention of gastric cancer. Of the 148 studies found in the Medline database, 100 were discarded and 48 were reviewed. According to the analysis presented, these studies were classified as: epidemiology of gastric cancer (5/48); risk factors and protectors relating to gastric cancer (9/48); relationship between Helicobacter pylori and pathologies associated with gastric cancer and the development of the disease (16/48); relationship between the Epstein-Barr virus and pathologies associated with gastric cancer and the development of the disease (3/48); molecular markers for the development of diseases associated with gastric cancer and gastric cancer (15/48). Mexico requires a program for the prevention and control of gastric cancer based on national health indicators. This should be produced by a multidisciplinary committee of experts who can propose actions that are relevant in the current national context. The few studies of gastric cancer conducted on the Mexican population in national institutes highlight the poor connection that currently exists between the scientific community and the health sector in terms of resolving this health issue. Public policies for health research should support projects with findings that can be translated into benefits for the population. This review serves to identify national research groups studying gastric cancer in the Mexican

  11. Reproductive factors, hormone use and gastric cancer risk: The Singapore Chinese Health Study.

    PubMed

    Wang, Zhensheng; Butler, Lesley M; Wu, Anna H; Koh, Woon-Puay; Jin, Aizhen; Wang, Renwei; Yuan, Jian-Min

    2016-06-15

    Gastric cancer incidence varies greatly worldwide, but is consistently twice as high in men than in women. The hormone-related factors hypothesized to be associated with lower risk of gastric cancer in women have not been fully explored in populations with a high background risk of gastric cancer. The Singapore Chinese Health Study (SCHS) is a prospective cohort study in which 34,022 of the participants enrolled between 1993 and 1998 were women between 45 and 74 years of age. Information on reproductive histories, hormone replacement therapy (HRT) and oral contraceptive (OC) use was collected through in-person interviews at baseline. As of December 31, 2013, 269 incident gastric cancer cases were identified. Multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to evaluate gastric cancer risk associations. Older age at natural menopause (≥55 versus <45 years: HR = 0.50, 95% CI: 0.25-0.99), type of menopause (other versus natural: HR = 0.48, 95% CI: 0.27-0.87) and greater years of menstrual cycling (fourth versus first quartile: HR = 0.67, 95% CI: 0.46-0.96) were associated with a decreased risk of gastric cancer. Ever use of OCs and HRT was also associated with reduced risk of gastric cancer; the multivariable-adjusted HRs (95% CIs) were 0.40 (0.17-0.90) for use of HRT >3 years and 0.67 (0.47-0.94) for ever use of OCs, compared with never use. Reproductive factors associated with a longer window of fertility and the use of exogenous hormones were shown to reduce gastric cancer development in a cohort of Chinese women with a high background risk of gastric cancer.

  12. Solitary Spinal Epidural Metastasis from Gastric Cancer

    PubMed Central

    Sako, Taisei; Iida, Yasuaki; Yokoyama, Yuichirou; Tsuge, Shintaro; Hasegawa, Keiji; Wada, Akihito; Mikami, Tetsuo

    2016-01-01

    Solitary epidural space metastasis of a malignant tumor is rare. We encountered a 79-year-old male patient with solitary metastatic epidural tumor who developed paraplegia and dysuria. The patient had undergone total gastrectomy for gastric cancer followed by chemotherapy 8 months priorly. The whole body was examined for suspected metastatic spinal tumor, but no metastases of the spine or important organs were observed, and a solitary mass was present in the thoracic spinal epidural space. The mass was excised for diagnosis and treatment and was histopathologically diagnosed as metastasis from gastric cancer. No solitary metastatic epidural tumor from gastric cancer has been reported in English. Among the Japanese, 3 cases have been reported, in which the outcome was poor in all cases and no definite diagnosis could be made before surgery in any case. Our patient developed concomitant pneumonia after surgery and died shortly after the surgery. When a patient has a past medical history of malignant tumor, the possibility of a solitary metastatic tumor in the epidural space should be considered. PMID:27703825

  13. Borrmann Type 4 Advanced Gastric Cancer: Focus on the Development of Scirrhous Gastric Cancer

    PubMed Central

    Jung, Kyoungwon; Park, Moo In; Kim, Sung Eun; Park, Seun Ja

    2016-01-01

    Early diagnosis of Borrmann type 4 advanced gastric cancer (AGC) is very important for improving the prognosis of AGC patients. Because there is no definite mass in most cases of Borrmann type 4 AGC, its accurate diagnosis via endoscopy requires an understanding of its pathogenesis and developmental process. Moreover, many people confuse linitis plastica (LP) type gastric cancer (GC), scirrhous GC, and Borrmann type 4 AGC. To distinguish each of these cancers, knowledge of their endoscopic and pathological differences is necessary, especially for LP type GCs in the developmental stage. In conclusion, diagnosis of pre-stage or latent LP type GC before progression to typical LP type GC requires the detection of IIc-like lesions in the fundic gland area. It is also crucial to identify any abnormalities such as sclerosis of the gastric wall and hypertrophy of the mucosal folds during endoscopy. PMID:27456608

  14. Decreased Core-Fucosylation Contributes to Malignancy in Gastric Cancer

    PubMed Central

    Wang, Hao; You, Qing; Yi, Chang-Hong; Ji, Jun; Gu, Xing; Zhou, Ping-Ting; Cheng, Cheng; Gao, Chun-Fang

    2014-01-01

    The object of the study is to identify N-glycan profiling changes associated with gastric cancer and explore the impact of core-fucosylation on biological behaviors of human gastric cancer cells. A total of 244 subjects including gastric cancer, gastric ulcer and healthy control were recruited. N-glycan profiling from serum and total proteins in gastric tissues was analyzed by DNA sequencer-assisted fluorophore-assisted capillary electrophoresis. The abundance of total core-fucosylated residues and the expression of enzymes involved in core-fucosylation were analyzed with lectin blot, quantitative reverse transcription-polymerase chain reaction, western blot, Immunohistochemical staining and lectin-histochemical staining. The recombinant plasmids of GDP-fucose transporter and α-1,6-fucosyltransferase (Fut8) were constructed and transfected into gastric cancer cell lines BGC-823 and SGC-7901. CCK-8 and wound healing assay were used to assess the functional impact of core-fucosylation modulation on cell proliferation and migration. Characteristic serum N-glycan profiles were found in gastric cancer. Compared with the healthy control, a trianntenary structure abundance, peak 9 (NA3Fb), was increased significantly in gastric cancer, while the total abundance of core-fucosylated residues (sumfuc) was decreased. Core-fucosylated structures, peak6(NA2F) and peak7(NA2FB) were deceased in gastric tumor tissues when compared with that in adjacent non-tumor tissues. Consistently, lens culinaris agglutinin (LCA)-binding proteins were decreased significantly in sera of gastric cancer, and protein level of Fut8 was decreased significantly in gastric tumor tissues compared with that in adjacent non-tumor tissues. Upregulation of GDP-Tr and Fut8 could inhibit proliferation, but had no significant influence on migration of BGC-823 and SGC-7901 cells. Core-fucosylation is down regulated in gastric cancer. Upregulation of core-fucosylation could inhibit proliferation of the human

  15. Downregulation of tumor suppressor QKI in gastric cancer and its implication in cancer prognosis

    SciTech Connect

    Bian, Yongqian; Wang, Li; Lu, Huanyu; Yang, Guodong; Zhang, Zhang; Fu, Haiyan; Lu, Xiaozhao; Wei, Mengying; Sun, Jianyong; Zhao, Qingchuan; Dong, Guanglong; Lu, Zifan

    2012-05-25

    Highlights: Black-Right-Pointing-Pointer QKI expression is decreased in gastric cancer samples. Black-Right-Pointing-Pointer Promoter hyper methylation contributes to the downregulation of QKI. Black-Right-Pointing-Pointer QKI inhibits the growth of gastric cancer cells. Black-Right-Pointing-Pointer Decreased QKI expression predicts poor survival. -- Abstract: Gastric cancer (GC) is the fourth most common cancer and second leading cause of cancer-related death worldwide. RNA-binding protein Quaking (QKI) is a newly identified tumor suppressor in multiple cancers, while its role in GC is largely unknown. Our study here aimed to clarify the relationship between QKI expression with the clinicopathologic characteristics and the prognosis of GC. In the 222 GC patients' specimens, QKI expression was found to be significantly decreased in most of the GC tissues, which was largely due to promoter hypermethylation. QKI overexpression reduced the proliferation ability of GC cell line in vitro study. In addition, the reduced QKI expression correlated well with poor differentiation status, depth of invasion, gastric lymph node metastasis, distant metastasis, advanced TNM stage, and poor survival. Multivariate analysis showed QKI expression was an independent prognostic factor for patient survival.

  16. Screening for and surveillance of gastric cancer

    PubMed Central

    Compare, Debora; Rocco, Alba; Nardone, Gerardo

    2014-01-01

    Although the prevalence of gastric cancer (GC) progressively decreased during the last decades, due to improved dietary habit, introduction of food refrigeration and recovered socio-economic level, it still accounts for 10% of the total cancer-related deaths. The best strategy to reduce the mortality for GC is to schedule appropriate screening and surveillance programs, that rises many relevant concerns taking into account its worldwide variability, natural history, diagnostic tools, therapeutic strategies, and cost-effectiveness. Intestinal-type, the most frequent GC histotype, develops through a multistep process triggered by Helicobacter pylori (H. pylori) and progressing from gastritis to atrophy, intestinal metaplasia (IM), and dysplasia. However, the majority of patients infected with H. pylori and carrying premalignant lesions do not develop GC. Therefore, it remains unclear who should be screened, when the screening should be started and how the screening should be performed. It seems reasonable that screening programs should target the general population in eastern countries, at high prevalence of GC and the high-risk subjects in western countries, at low prevalence of GC. As far as concern surveillance, currently, we are lacking of standardized international recommendations and many features have to be defined regarding the optimal diagnostic approach, the patients at higher risk, the best timing and the cost-effectiveness. Anyway, patients with corpus atrophic gastritis, extensive incomplete IM and dysplasia should enter a surveillance program. At present, screening and surveillance programs need further studies to draw worldwide reliable recommendations and evaluate the impact on mortality for GC. PMID:25320506

  17. Dehydroeffusol effectively inhibits human gastric cancer cell-mediated vasculogenic mimicry with low toxicity

    SciTech Connect

    Liu, Wenming; Meng, Mei; Zhang, Bin; Du, Longsheng; Pan, Yanyan; Yang, Ping; Gu, Zhenlun; Zhou, Quansheng Cao, Zhifei

    2015-09-01

    Accumulated data has shown that various vasculogenic tumor cells, including gastric cancer cells, are able to directly form tumor blood vessels via vasculogenic mimicry, supplying oxygen and nutrients to tumors, and facilitating progression and metastasis of malignant tumors. Therefore, tumor vasculogenic mimicry is a rational target for developing novel anticancer therapeutics. However, effective antitumor vasculogenic mimicry-targeting drugs are not clinically available. In this study, we purified 2,7-dihydroxyl-1-methyl-5-vinyl-phenanthrene, termed dehydroeffusol, from the traditional Chinese medicinal herb Juncus effusus L., and found that dehydroeffusol effectively inhibited gastric cancer cell-mediated vasculogenic mimicry in vitro and in vivo with very low toxicity. Dehydroeffusol significantly suppressed gastric cancer cell adhesion, migration, and invasion. Molecular mechanistic studies revealed that dehydroeffusol markedly inhibited the expression of a vasculogenic mimicry master gene VE-cadherin and reduced adherent protein exposure on the cell surface by inhibiting gene promoter activity. In addition, dehydroeffusol significantly decreased the expression of a key vasculogenic gene matrix metalloproteinase 2 (MMP2) in gastric cancer cells, and diminished MMP2 protease activity. Together, our results showed that dehydroeffusol effectively inhibited gastric cancer cell-mediated vasculogenic mimicry with very low toxicity, suggesting that dehydroeffusol is a potential drug candidate for anti-gastric cancer neovascularization and anti-gastric cancer therapy. - Highlights: • Dehydroeffusol markedly inhibits gastric cancer cell-mediated vasculogenic mimicry. • Dehydroeffusol suppresses the expression of vasculogenic mimicry key gene VE-cadherin. • Dehydroeffusol decreases the MMP2 expression and activity in gastric cancer cells. • Dehydroeffusol is a potential anti-cancer drug candidate with very low toxicity.

  18. Differential Proteomic Analysis of Human Saliva using Tandem Mass Tags Quantification for Gastric Cancer Detection

    PubMed Central

    Xiao, Hua; Zhang, Yan; Kim, Yong; Kim, Sung; Kim, Jae Joon; Kim, Kyoung Mee; Yoshizawa, Janice; Fan, Liu-Yin; Cao, Cheng-Xi; Wong, David T. W.

    2016-01-01

    Novel biomarkers and non-invasive diagnostic methods are urgently needed for the screening of gastric cancer to reduce its high mortality. We employed quantitative proteomics approach to develop discriminatory biomarker signatures from human saliva for the detection of gastric cancer. Salivary proteins were analyzed and compared between gastric cancer patients and matched control subjects by using tandem mass tags (TMT) technology. More than 500 proteins were identified with quantification, and 48 of them showed significant difference expression (p < 0.05) between normal controls and gastric cancer patients, including 7 up-regulated proteins and 41 down-regulated proteins. Five proteins were selected for initial verification by ELISA and three were successfully verified, namely cystatin B (CSTB), triosephosphate isomerase (TPI1), and deleted in malignant brain tumors 1 protein (DMBT1). All three proteins could differentiate gastric cancer patients from normal control subjects, dramatically (p < 0.05). The combination of these three biomarkers could reach 85% sensitivity and 80% specificity for the detection of gastric cancer with accuracy of 0.93. This study provides the proof of concept of salivary biomarkers for the non-invasive detection of gastric cancer. It is highly encouraging to turn these biomarkers into an applicable clinical test after large scale validation. PMID:26911362

  19. Dehydroeffusol effectively inhibits human gastric cancer cell-mediated vasculogenic mimicry with low toxicity.

    PubMed

    Liu, Wenming; Meng, Mei; Zhang, Bin; Du, Longsheng; Pan, Yanyan; Yang, Ping; Gu, Zhenlun; Zhou, Quansheng; Cao, Zhifei

    2015-09-01

    Accumulated data has shown that various vasculogenic tumor cells, including gastric cancer cells, are able to directly form tumor blood vessels via vasculogenic mimicry, supplying oxygen and nutrients to tumors, and facilitating progression and metastasis of malignant tumors. Therefore, tumor vasculogenic mimicry is a rational target for developing novel anticancer therapeutics. However, effective antitumor vasculogenic mimicry-targeting drugs are not clinically available. In this study, we purified 2,7-dihydroxyl-1-methyl-5-vinyl-phenanthrene, termed dehydroeffusol, from the traditional Chinese medicinal herb Juncus effusus L., and found that dehydroeffusol effectively inhibited gastric cancer cell-mediated vasculogenic mimicry in vitro and in vivo with very low toxicity. Dehydroeffusol significantly suppressed gastric cancer cell adhesion, migration, and invasion. Molecular mechanistic studies revealed that dehydroeffusol markedly inhibited the expression of a vasculogenic mimicry master gene VE-cadherin and reduced adherent protein exposure on the cell surface by inhibiting gene promoter activity. In addition, dehydroeffusol significantly decreased the expression of a key vasculogenic gene matrix metalloproteinase 2 (MMP2) in gastric cancer cells, and diminished MMP2 protease activity. Together, our results showed that dehydroeffusol effectively inhibited gastric cancer cell-mediated vasculogenic mimicry with very low toxicity, suggesting that dehydroeffusol is a potential drug candidate for anti-gastric cancer neovascularization and anti-gastric cancer therapy.

  20. Cancer type-specific epigenetic changes: gastric cancer.

    PubMed

    Calcagno, Danielle Queiroz; de Arruda Cardoso Smith, Marília; Burbano, Rommel Rodriguez

    2015-01-01

    Gastric cancer (GC) remains a major cause of mortality despite declining rate in the world. Epigenetic alterations contribute significantly to the development and progression of gastric tumors. Epigenetic refers to the number of modifications of the chromatin structure that affect gene expression without altering the primary sequence of DNA, and these changes lead to transcriptional activation or silencing of the gene. Over the years, the study of epigenetic processes has increased, and novel therapeutic approaches have emerged. This chapter summarizes the main epigenomic mechanisms described recently involved in gastric carcinogenesis, focusing on the roles that aberrant DNA methylation, histone modifications (histone acetylation and methylation), and miRNAs (oncogenic and tumor suppressor function of miRNA) play in the onset and progression of gastric tumors. Clinical implications of these epigenetic alterations in GC are also discussed.

  1. Cancer type-specific epigenetic changes: gastric cancer.

    PubMed

    Calcagno, Danielle Queiroz; de Arruda Cardoso Smith, Marília; Burbano, Rommel Rodriguez

    2015-01-01

    Gastric cancer (GC) remains a major cause of mortality despite declining rate in the world. Epigenetic alterations contribute significantly to the development and progression of gastric tumors. Epigenetic refers to the number of modifications of the chromatin structure that affect gene expression without altering the primary sequence of DNA, and these changes lead to transcriptional activation or silencing of the gene. Over the years, the study of epigenetic processes has increased, and novel therapeutic approaches have emerged. This chapter summarizes the main epigenomic mechanisms described recently involved in gastric carcinogenesis, focusing on the roles that aberrant DNA methylation, histone modifications (histone acetylation and methylation), and miRNAs (oncogenic and tumor suppressor function of miRNA) play in the onset and progression of gastric tumors. Clinical implications of these epigenetic alterations in GC are also discussed. PMID:25421656

  2. R-flurbiprofen reverses multidrug resistance, proliferation and metastasis in gastric cancer cells by p75(NTR) induction.

    PubMed

    Jin, Haifeng; Wang, Zhipeng; Liu, Lili; Gao, Liucun; Sun, Li; Li, Xiaohua; Zhao, Hongxi; Pan, Yanglin; Shi, Hai; Liu, Na; Hong, Liu; Liang, Jie; Wu, Qiong; Yang, Zhiping; Wu, Kaichun; Fan, Daiming

    2010-02-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) can inhibit cell growth and metastasis, and induce cell apoptosis in cancerous cells. They have been shown to reduce incidence and mortality of gastric cancer by an unknown mechanism. NSAIDs often exert their effects by Cox-2 inhibition, and Cox-2 is overexpressed in gastric cancer cells. Nevertheless, when gastric cancer cells were treated with different NSAIDs, the non-Cox-2-inhibiting R-flurbiprofen was most effective at reducing proliferation of gastric cancer cells in vitro. R-Flurbiprofen prevented the metastatic characteristics of gastric cancer cells in vitro, and reduced tumor size and metastasis in vitro, when gastric cancer cells were injected into nude mice. R-Flurbiprofen also affected multidrug resistance, increasing the sensitivity of resistant gastric cancer cells to chemotherapeutic agents. Mechanistically, R-flurbiprofen was found to have pleiotropic effects, changing levels of cell cycle factors like Cyclin D1 and CKD4, apoptotic protwins like caspase3 and Bcl-2, and protwins that affect metastasis, like metalloproteases. Consistent with reports on other cancer cell types, NSAID treatment with R-flurbiprofen increased levels of the tumor suppressor neurotrophin receptor (p75(NTR)) in gastric cancer cells. The anticancer effects of R-flurbiprofen were found to require induction of p75(NTR) via the p38 signaling pathway, suggesting a possible mechanism of action. PMID:19916560

  3. Synthesis, identification and in vivo studies of tumor-targeting agent peptide doxorubicin (PDOX) to treat peritoneal carcinomatosis of gastric cancer with similar efficacy but reduced toxicity

    PubMed Central

    2014-01-01

    Background This work aimed to synthesize a cathepsin B (CTSB)-cleavable tumor-targeting prodrug peptide doxorubicin (PDOX) and study the in vivo efficacy and toxicities on an animal model of gastric peritoneal carcinomatosis (PC). Methods PDOX was synthesized using doxorubicin (DOX) attaching to a CTSB-cleavable dipeptide Ac-Phe-Lys and a para-amino-benzyloxycarbonyl (PABC) spacer. PC model was established by injecting VX2 tumor cells into the gastric sub-mucosa of 40 rabbits, which then were randomized into 4 groups: the Control (n = 10) without treatment, the HIPEC (n = 10) receiving cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC), the PDOX (n = 10) and the DOX (n = 10) receiving systemic chemotherapy with PDOX 50.0 mg/kg or DOX 5.0 mg/kg, respectively, after CRS + HIPEC. Results The median overall survivals (OS) were 23.0 d (95% CI: 19.9 d - 26.1 d) in the Control, 41.0 d (36.9 d - 45.1 d) in the HIPEC, 65.0 d (44.1 d - 71.9 d) in the PDOX, and 58.0 d (39.6 d - 54.4 d) in the DOX. Compared with the Control, the OS was extended by 70% in the HIPEC (p < 0.001) and further extended by 40% in the DOX (p = 0.029) and by 58% in the PDOX (p = 0.021), and the PC severity was decreased in the HIPEC and further decreased in the PDOX and DOX. Animals receiving DOX treatment showed hematological toxicities with marked reduction of white blood cells and platelets, as well as cardiac toxicities with significant increases in creatine kinase mb isoenzyme, evident myocardium coagulation necrosis, significant nuclear degeneration, peri-nucleus mitochondria deletion, mitochondria-pyknosis, and abnormal intercalated discs. But these toxicities were not evident in the PDOX. Conclusions PDOX is a newly synthesized tumor-targeting prodrug of DOX. Compared with DOX, PDOX has similar efficacy but reduced hematological and cardiac toxicities in treating rabbit model of gastric PC. PMID:24588871

  4. Pylorus-Preserving Gastrectomy for Gastric Cancer.

    PubMed

    Oh, Seung-Young; Lee, Hyuk-Joon; Yang, Han-Kwang

    2016-06-01

    Pylorus-preserving gastrectomy (PPG) is a function-preserving surgery for the treatment of early gastric cancer (EGC), aiming to decrease the complication rate and improve postoperative quality of life. According to the Japanese gastric cancer treatment guidelines, PPG can be performed for cT1N0M0 gastric cancer located in the middle-third of the stomach, at least 4.0 cm away from the pylorus. Although the length of the antral cuff gradually increased, from 1.5 cm during the initial use of the procedure to 3.0 cm currently, its optimal length still remains unclear. Standard procedures for the preservation of pyloric function, infra-pyloric vessels, and hepatic branch of the vagus nerve, make PPG technically more difficult and raise concerns about incomplete lymph node dissection. The short- and long-term oncological and survival outcomes of PPG were comparable to those for distal gastrectomy, but with several advantages such as a lower incidence of dumping syndrome, bile reflux, and gallstone formation, and improved nutritional status. Gastric stasis, a typical complication of PPG, can be effectively treated by balloon dilatation and stent insertion. Robot-assisted pylorus-preserving gastrectomy is feasible for EGC in the middle-third of the stomach in terms of the short-term clinical outcome. However, any benefits over laparoscopy-assisted PPG (LAPPG) from the patient's perspective have not yet been proven. An ongoing Korean multicenter randomized controlled trial (KLASS-04), which compares LAPPG and laparoscopy-assisted distal gastrectomy for EGC in the middle-third of the stomach, may provide more clear evidence about the advantages and oncologic safety of PPG. PMID:27433390

  5. Eosinophilic gastroenteritis associated with multiple gastric cancer.

    PubMed

    Otowa, Yasunori; Mitsutsuji, Masaaki; Urade, Takeshi; Chono, Teruhiro; Morimoto, Haruki; Yokoyama, Kunio; Hirata, Kenro; Kawamura, Shiro; Shimada, Etsuji; Fujita, Masayuki

    2012-06-01

    Eosinophilic gastroenteritis (EG) is an inflammation of the digestive tract that is characterized by eosinophilic infiltration. There are no specific symptoms, and are related to the layer in which eosinophilic infiltration is observed. A 69-year-old Japanese man presented to our hospital with a history of general malaise, diarrhea, and dysgeusia. Esophagogastroduodenoscopy showed reddish elevated lesions that were edematous all over the gastric mucosa. In addition, three tumors were also observed. The biopsies of the reddish elevated mucosa revealed eosinophilic infiltration and tubular adenocarcinoma from the tumors. Colonoscopy showed abnormal reddish elevated mucosa. The biopsies from the reddish elevated mucosa showed eosinophilic infiltration. From the abdominal contrast computed tomography scan, tumor stain was seen in the anterior wall of the gastric body. No ascites, intestinal wall thickening, or lymph node swelling were found. A slight elevation in the serum immunoglobulin E (IgE), 480 IU/ml, was found from the laboratory test results; other laboratory results were within normal limits including the number of peripheral eosinophils. No specific allergen was found from the multiple antigen simultaneous test and from the skin patch test. The parasitic immunodiagnosis was negative. He was diagnosed with EG associated with gastric cancer and underwent total gastrectomy, regional lymph node dissection with reconstruction by a Roux-en-Y method. He was prescribed prednisolone after the operation and showed a good clinical response. There are many case reports on EG, but none of them were associated with cancer. We encountered a case of EG associated with multiple gastric cancer; the patient underwent total gastrectomy.

  6. Pylorus-Preserving Gastrectomy for Gastric Cancer

    PubMed Central

    Oh, Seung-Young; Yang, Han-Kwang

    2016-01-01

    Pylorus-preserving gastrectomy (PPG) is a function-preserving surgery for the treatment of early gastric cancer (EGC), aiming to decrease the complication rate and improve postoperative quality of life. According to the Japanese gastric cancer treatment guidelines, PPG can be performed for cT1N0M0 gastric cancer located in the middle-third of the stomach, at least 4.0 cm away from the pylorus. Although the length of the antral cuff gradually increased, from 1.5 cm during the initial use of the procedure to 3.0 cm currently, its optimal length still remains unclear. Standard procedures for the preservation of pyloric function, infra-pyloric vessels, and hepatic branch of the vagus nerve, make PPG technically more difficult and raise concerns about incomplete lymph node dissection. The short- and long-term oncological and survival outcomes of PPG were comparable to those for distal gastrectomy, but with several advantages such as a lower incidence of dumping syndrome, bile reflux, and gallstone formation, and improved nutritional status. Gastric stasis, a typical complication of PPG, can be effectively treated by balloon dilatation and stent insertion. Robot-assisted pylorus-preserving gastrectomy is feasible for EGC in the middle-third of the stomach in terms of the short-term clinical outcome. However, any benefits over laparoscopy-assisted PPG (LAPPG) from the patient's perspective have not yet been proven. An ongoing Korean multicenter randomized controlled trial (KLASS-04), which compares LAPPG and laparoscopy-assisted distal gastrectomy for EGC in the middle-third of the stomach, may provide more clear evidence about the advantages and oncologic safety of PPG. PMID:27433390

  7. CEACAM6 promotes tumor angiogenesis and vasculogenic mimicry in gastric cancer via FAK signaling.

    PubMed

    Zang, Mingde; Zhang, Yunqiang; Zhang, Baogui; Hu, Lei; Li, Jianfang; Fan, Zhiyuan; Wang, Hexiao; Su, Liping; Zhu, Zhenggang; Li, Chen; Yan, Chao; Gu, Qinlong; Liu, Bingya; Yan, Min

    2015-05-01

    CEACAM6 is a member of glycosylphosphatidylinositol-linked immunoglobulin superfamily that is implicated in a variety of human cancers. In our previous study, we reported that CEACAM6 was overexpressed in gastric cancer tissues and promoted cancer metastasis. The purpose of this study is to determine the role of CEACAM6 in tumor angiogenesis and mimicry formation. We found that overexpressed CEACAM6 promoted tubule formation dependent on HUVEC cells and vasculogenic mimicry formation of gastric cancer cells; opposing results were achieved in CEACAM6-silenced groups. Moreover, we found that mosaic vessels formed by HUVEC cells and gastric cancer cells were observed in vitro by 3D-culture assay. Overexpressed CEACAM6 in gastric cancer cells promoted tumor growth, VEGF expression and vasculogenic mimicry structures formation in vivo. In accordance with these observations, we found that phosphorylation of FAK and phosphorylation of paxillin were up-regulated in CEACAM6-overexpressing gastric cancer cells, and FAK inhibitor Y15 could reduce tubule and vasculogenic mimicry formation. These findings suggest that CEACAM6 promotes tumor angiogenesis and vasculogenic mimicry formation via FAK signaling in gastric cancer and CEACAM6 may be a new target for cancer anti-vascular treatment.

  8. Gastric cancer: Prevention, screening and early diagnosis

    PubMed Central

    Pasechnikov, Victor; Chukov, Sergej; Fedorov, Evgeny; Kikuste, Ilze; Leja, Marcis

    2014-01-01

    Gastric cancer continues to be an important healthcare problem from a global perspective. Most of the cases in the Western world are diagnosed at late stages when the treatment is largely ineffective. Helicobacter pylori (H. pylori) infection is a well-established carcinogen for gastric cancer. While lifestyle factors are important, the efficacy of interventions in their modification, as in the use of antioxidant supplements, is unconvincing. No organized screening programs can be found outside Asia (Japan and South Korea). Although several screening approaches have been proposed, including indirect atrophy detection by measuring pepsinogen in the circulation, none of them have so far been implemented, and more study data is required to justify any implementation. Mass eradication of H. pylori in high-risk areas tends to be cost-effective, but its adverse effects and resistance remain a concern. Searches for new screening biomarkers, including microRNA and cancer-autoantibody panels, as well as detection of volatile organic compounds in the breath, are in progress. Endoscopy with a proper biopsy follow-up remains the standard for early detection of cancer and related premalignant lesions. At the same time, new advanced high-resolution endoscopic technologies are showing promising results with respect to diagnosing mucosal lesions visually and targeting each biopsy. New histological risk stratifications (classifications), including OLGA and OLGIM, have recently been developed. This review addresses the current means for gastric cancer primary and secondary prevention, the available and emerging methods for screening, and new developments in endoscopic detection of early lesions of the stomach. PMID:25320521

  9. Expression of stem cell markers nanog and PSCA in gastric cancer and its significance

    PubMed Central

    ZHAO, XUANZHONG; WANG, FENG; HOU, MINGXING

    2016-01-01

    The present study aimed to determine the expression of stem cell markers Nanog compared with PSCA in gastric cancer tissues and adjacent normal tissues, and to investigate the association between tumor stem cells and initiation, progression, metastasis, and prognosis of gastric cancer. One hundred chemotherapy- and radiotherapy-naive patients with pathologically confirmed gastric cancer were enrolled from the General Surgery Department and Surgical Oncology Department of the Affiliated Hospital of Inner Mongolia Medical University (Hohhot, P.R. China), between October 2011 and June 2013. Surgically resected specimens of cancer tissues and adjacent normal tissues (>5 cm from the boundary of cancerous component) were collected. The mRNA expression levels of Nanog and PSCA in those tissues was determined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The correlation between the expression of stem cell markers Nanog and PSCA in gastric cancer tissues and clinicopathological factors was analyzed. The qPCR results demonstrated that the relative expression of Nanog was increased in gastric cancer tissues compared with in the adjacent tissues (P<0.05); and relative expression of PSCA was reduced in gastric cancer tissues compared with adjacent tissues (P<0.05). The expression of Nanog and PSCA in gastric cancer tissues was associated with tumor differentiation. The expression of Nanog was increased in poorly-differentiated and undifferentiated tumors compared with moderately- and well-differentiated tumors (P<0.05). The expression of PSCA was reduced in poorly differentiated and undifferentiated tumors compared with moderately- and well-differentiated tumors (P<0.05). However, the expression of Nanog and PSCA was not associated with age, gender, tumor size, TNM stage, depth of invasion, or lymph node metastasis. Therefore, Nanog and PSCA may have potential as molecular markers to reflect the differentiation status of gastric cancer. PMID

  10. Strategies for eliminating death from gastric cancer in Japan

    PubMed Central

    ASAKA, Masahiro; MABE, Katsuhiro

    2014-01-01

    In Japan, efforts have been directed toward improving the detection of early gastric cancer by double contrast radiography and endoscopy, since early cancer has a good prognosis, resulting in Japan having the world’s best diagnostic system for early gastric cancer. The 5-year survival rate of gastric cancer patients in Japan is much higher than in Western countries by the development of endoscopic treatment for early gastric cancer. In February 2013, Japanese national health insurance cover for H. pylori eradication therapy was expanded to patients with H. pylori-associated gastritis, a type of chronic gastritis. H. pylori-associated gastritis causes gastric and duodenal ulcers and gastric polyps, therefore, providing treatment for this gastritis is likely to substantially decrease the prevalence of both gastric and duodenal ulcer and gastric cancer. Patients with gastritis are tested for H. pylori infection and those who are positive receive eradication therapy followed by periodic endoscopic surveillance. If such an approach is pursued further in Japan, gastric cancer deaths will show a dramatic decline after 10–20 years. PMID:25169671

  11. Prognostic value of decreased expression of RBM4 in human gastric cancer

    PubMed Central

    Yong, Hongmei; Zhu, Huijun; Zhang, Shu; Zhao, Wei; Wang, Wei; Chen, Chen; Ding, Guipeng; Zhu, Lun; Zhu, Ziyuan; Liu, Huaidong; Zhang, Yongjie; Wen, Jinbo; Kang, Xing; Zhu, Jin; Feng, Zhenqing; Liu, Baorui

    2016-01-01

    RNA-binding motif 4 (RBM4) is a multifunctional protein that participates in regulating alternative splicing and mRNA translation. Its reduced expression has been associated with poor overall survival in lung cancer, breast cancer and ovarian cancer. We assessed RBM4 protein expression levels with immunohistochemistry in tissue microarrays containing malignant gastric cancer tissues and benign tissues from 813 patients. We also examined the expression levels of RBM4 mRNA in twenty-five paired gastric cancer samples and adjacent noncancerous tissues. Both RBM4 protein and mRNA expression levels were significantly lower in gastric cancer tissues compared with the adjacent noncancerous tissues. There was a significant association between reduced RBM4 protein expression and differentiation (P < 0.001), lymph node metastasis (P = 0.026), TNM state (P = 0.014) and distant metastasis (P = 0.036). Patients with reduced RBM4 expression (P < 0.001, CI = 0.315–0.710) and TNM stage III and IV (P < 0.001, CI = 4.757–11.166) had a poor overall survival. These findings suggest that RBM4 is a new biomarker in gastric cancer, as the reduced expression of this protein is correlated with poor differentiation, lymph node status and distant metastasis. Further, lower RBM4 expression is an independent prognostic marker for gastric cancer. PMID:27324405

  12. Mouse models for gastric cancer: Matching models to biological questions.

    PubMed

    Poh, Ashleigh R; O'Donoghue, Robert J J; Ernst, Matthias; Putoczki, Tracy L

    2016-07-01

    Gastric cancer is the third leading cause of cancer-related mortality worldwide. This is in part due to the asymptomatic nature of the disease, which often results in late-stage diagnosis, at which point there are limited treatment options. Even when treated successfully, gastric cancer patients have a high risk of tumor recurrence and acquired drug resistance. It is vital to gain a better understanding of the molecular mechanisms underlying gastric cancer pathogenesis to facilitate the design of new-targeted therapies that may improve patient survival. A number of chemically and genetically engineered mouse models of gastric cancer have provided significant insight into the contribution of genetic and environmental factors to disease onset and progression. This review outlines the strengths and limitations of current mouse models of gastric cancer and their relevance to the pre-clinical development of new therapeutics. PMID:26809278

  13. Mouse models for gastric cancer: Matching models to biological questions.

    PubMed

    Poh, Ashleigh R; O'Donoghue, Robert J J; Ernst, Matthias; Putoczki, Tracy L

    2016-07-01

    Gastric cancer is the third leading cause of cancer-related mortality worldwide. This is in part due to the asymptomatic nature of the disease, which often results in late-stage diagnosis, at which point there are limited treatment options. Even when treated successfully, gastric cancer patients have a high risk of tumor recurrence and acquired drug resistance. It is vital to gain a better understanding of the molecular mechanisms underlying gastric cancer pathogenesis to facilitate the design of new-targeted therapies that may improve patient survival. A number of chemically and genetically engineered mouse models of gastric cancer have provided significant insight into the contribution of genetic and environmental factors to disease onset and progression. This review outlines the strengths and limitations of current mouse models of gastric cancer and their relevance to the pre-clinical development of new therapeutics.

  14. Specific expression and methylation of SLIT1, SLIT2, SLIT3, and miR-218 in gastric cancer subtypes.

    PubMed

    Kim, Mirang; Kim, Jong-Hwan; Baek, Su-Jin; Kim, Seon-Young; Kim, Yong Sung

    2016-06-01

    SLIT has been suggested as a key regulator of cancer development and a promising therapeutic target for cancer treatment. Herein, we analyzed expression and methylation of SLIT1/SLIT2/SLIT3 in 11 gastric cancer cell lines, 96 paired gastric tumors and adjacent normal gastric tissues, and 250 gastric cancers provided by The Cancer Genome Atlas. Methylation of SLIT1/SLIT2/SLIT3 was found both in early gastric cancers, and in advanced gastric cancers. Even normal gastric tissue showed increased methylation of SLIT1 and SLIT3 that correlated with patient age. Furthermore, epigenetic inactivation of SLIT occurred in a gastric cancer subtype-dependent manner. SLIT2 and SLIT3 expression was reduced in Epstein-Barr virus-positive and microsatellite instability subtypes, but increased in the genomically stable subtype. Expression of miR‑218 correlated negatively with methylation of SLIT2 or SLIT3. These findings suggest that a molecular subtype-specific therapeutic strategy is needed for targeting SLITs and miR-218 in treatment of gastric cancer.

  15. EF24 induces ROS-mediated apoptosis via targeting thioredoxin reductase 1 in gastric cancer cells

    PubMed Central

    Chen, Weiqian; Chen, Xi; Ying, Shilong; Feng, Zhiguo; Chen, Tongke; Ye, Qingqing; Wang, Zhe; Qiu, Chenyu; Yang, Shulin; Liang, Guang

    2016-01-01

    Gastric cancer (GC) is one of the leading causes of cancer mortality in the world, and finding novel agents for the treatment of advanced gastric cancer is of urgent need. Diphenyl difluoroketone (EF24), a molecule having structural similarity to curcumin, exhibits potent anti-tumor activities by arresting cell cycle and inducing apoptosis. Although EF24 demonstrates potent anticancer efficacy in numerous types of human cancer cells, the cellular targets of EF24 have not been fully defined. We report here that EF24 may interact with the thioredoxin reductase 1 (TrxR1), an important selenocysteine (Sec)-containing antioxidant enzyme, to induce reactive oxygen species (ROS)-mediated apoptosis in human gastric cancer cells. By inhibiting TrxR1 activity and increasing intracellular ROS levels, EF24 induces a lethal endoplasmic reticulum stress in human gastric cancer cells. Importantly, knockdown of TrxR1 sensitizes cells to EF24 treatment. In vivo, EF24 treatment markedly reduces the TrxR1 activity and tumor cell burden, and displays synergistic lethality with 5-FU against gastric cancer cells. Targeting TrxR1 with EF24 thus discloses a previously unrecognized mechanism underlying the biological activity of EF24, and reveals that TrxR1 is a good target for gastric cancer therapy. PMID:26919110

  16. EF24 induces ROS-mediated apoptosis via targeting thioredoxin reductase 1 in gastric cancer cells.

    PubMed

    Zou, Peng; Xia, Yiqun; Chen, Weiqian; Chen, Xi; Ying, Shilong; Feng, Zhiguo; Chen, Tongke; Ye, Qingqing; Wang, Zhe; Qiu, Chenyu; Yang, Shulin; Liang, Guang

    2016-04-01

    Gastric cancer (GC) is one of the leading causes of cancer mortality in the world, and finding novel agents for the treatment of advanced gastric cancer is of urgent need. Diphenyl difluoroketone (EF24), a molecule having structural similarity to curcumin, exhibits potent anti-tumor activities by arresting cell cycle and inducing apoptosis. Although EF24 demonstrates potent anticancer effïcacy in numerous types of human cancer cells, the cellular targets of EF24 have not been fully defined. We report here that EF24 may interact with the thioredoxin reductase 1 (TrxR1), an important selenocysteine (Sec)-containing antioxidant enzyme, to induce reactive oxygen species (ROS)-mediated apoptosis in human gastric cancer cells. By inhibiting TrxR1 activity and increasing intracellular ROS levels, EF24 induces a lethal endoplasmic reticulum stress in human gastric cancer cells. Importantly, knockdown of TrxR1 sensitizes cells to EF24 treatment. In vivo, EF24 treatment markedly reduces the TrxR1 activity and tumor cell burden, and displays synergistic lethality with 5-FU against gastric cancer cells. Targeting TrxR1 with EF24 thus discloses a previously unrecognized mechanism underlying the biological activity of EF24, and reveals that TrxR1 is a good target for gastric cancer therapy. PMID:26919110

  17. Atractylenolide I-mediated Notch pathway inhibition attenuates gastric cancer stem cell traits

    SciTech Connect

    Ma, Li; Mao, Rurong; Shen, Ke; Zheng, Yuanhong; Li, Yueqi; Liu, Jianwen; Ni, Lei

    2014-07-18

    Highlights: • This paper supports the anti-tumor effects of AT-I on gastric cancer in vitro. • AT-I attenuates gastric cancer stem cell traits. • It is the systematic study regarding AT-I suppression of Notch pathway in GC and GCSLCs. - Abstract: Atractylenolide I (AT-I), one of the main naturally occurring compounds of Rhizoma Atractylodis Macrocephalae, has remarkable anti-cancer effects on various cancers. However, its effects on the treatment of gastric cancer remain unclear. Via multiple cellular and molecular approaches, we demonstrated that AT-I could potently inhibit cancer cell proliferation and induce apoptosis through inactivating Notch pathway. AT-I treatment led to the reduction of expressions of Notch1, Jagged1, and its downstream Hes1/ Hey1. Our results showed that AT-I inhibited the self-renewal capacity of gastric stem-like cells (GCSLCs) by suppression of their sphere formation capacity and cell viability. AT-I attenuated gastric cancer stem cell (GCSC) traits partly through inactivating Notch1, leading to reducing the expressions of its downstream target Hes1, Hey1 and CD44 in vitro. Collectively, our results suggest that AT-I might develop as a potential therapeutic drug for the treatment of gastric cancer.

  18. Deregulated expression of Nucleophosmin 1 in gastric cancer and its clinicopathological implications

    PubMed Central

    2014-01-01

    Background The process of gastric carcinogenesis still remains to be elucidated. The identification of genes related to this process may help to reduce mortality rates through early diagnosis and the development of new anticancer therapies. Nucleophosmin 1 (NPM1) acts in ribosome biogenesis, centrosome duplication, maintenance of genomic stability, and embryonic development. Recently, NPM1 has been implicated in the tumorigenesis processes. Here, we evaluated NPM1 gene and protein expression in gastric tumors and in corresponding non-neoplastic gastric samples. Methods NPM1 protein expression was determined by Western blot in 17 pairs of gastric tumors and corresponding non-neoplastic gastric tissue. The protein immunoreactivity was observed in 12 tumor samples. mRNA expression was evaluated by reverse transcription quantitative polymerase chain reaction (RT-qPCR) in 22 pairs of gastric tumors and in matched non-neoplastic gastric tissue. Results NPM1 protein expression was significantly reduced in gastric cancer samples compared to matched non-neoplastic gastric samples (P = 0.019). The protein level of NPM1 was reduced at least 1.5-fold in 35% of tumors compared to paired non-neoplastic gastric tissue. However, NPM1 immunoreactivity was detected in neoplastic and non-neoplastic cells, including in intestinal metaplastic, gastritis and inflammatory cells. NPM1 was mainly expressed in nucleus and nucleolus subcellular compartments. The staining intensity and the percentage of immunoreactive cells varied among the studied cases. The NPM1 mRNA level was reduced at least 1.5-fold in 45.5% of samples and increased in 27.3% of samples. An inverse correlation between protein and mRNA expression was detected (r = -0.509, P = 0.037). Intestinal-type gastric cancer presented higher mRNA levels than diffuse-type (P = 0.026). However, reduced NPM1 protein expression was associated with intestinal-type gastric cancer compared to matched non-neoplastic gastric

  19. Current advances in targeted therapies for metastatic gastric cancer: improving patient care.

    PubMed

    Aguiar, Pedro Nazareth; Muniz, Thiago Pimentel; Miranda, Raelson Rodrigues; Tadokoro, Hakaru; Forones, Nora Manoukian; Monteiro, Ines-de-Paula; Castelo-Branco, Pedro; Janjigian, Yelena Y; Mello, Ramon Andrade de

    2016-03-01

    In this article, we review the literature on the current advances in targeted therapies for metastatic gastric cancer aimed at improving patient care. We conclude that the key to guiding targeted therapy is individual biomarkers, which are not completely elucidated. HER2 overexpression is the only predictive biomarker currently in use. Furthermore, it is necessary to understand that gastric tumors are heterogeneous; therefore, is impossible to evaluate a novel biological compound without evaluating personal biomarkers. The selection of patients who are able to receive each treatment is paramount for improving advanced gastric cancer survival and reducing unnecessary costs.

  20. Estrogen receptors in gastric cancer: Advances and perspectives

    PubMed Central

    Rahman, Muhammad Saif Ur; Cao, Jiang

    2016-01-01

    Worldwide, gastric cancer is one of the most common malignancies with high mortality. Various aspects of the development and progression of gastric cancer continue to be extensively investigated in order to further our understanding and provide more effective means for the prevention, diagnosis, and treatment of the disease. Estrogen receptors (ERs) are steroid hormone receptors that regulate cellular activities in many physiological and pathological processes in different tissues. There are two distinct forms of ERs, namely ERα and ERβ, with several alternative-splicing isoforms for each. They show distinct tissue distribution patterns and exert different biological functions. Dysregulation of ERs has been found to be associated closely with many diseases, including cancer. A number of studies have been conducted to investigate the role of ERs in gastric cancer, the possible mechanisms underlying these roles, and the clinical relevance of deregulated ERs in gastric cancer patients. To date, inconsistent associations of different ERs with gastric cancer have been reported. These inconsistencies may be caused by variations in in vitro cell models and clinical samples, including assay conditions and protocols with regard to different forms of ERs. Given the potential of the deregulated ERs as diagnostic/prognostic markers or therapeutic targets for gastric cancer, it will be important to identify/confirm the association of each ER isoform with gastric cancer, to determine the specific roles and interactions that these individual ER isoforms play under specific conditions in the development and/or progression of gastric cancer, and to elucidate precisely these mechanisms. In this review, we summarize the achievements from early ER studies in gastric cancer to the most up-to-date discoveries, with an effort to provide a comprehensive understanding of the role of ERs roles in gastric cancer and its possible mechanisms. Furthermore, we propose directions for future

  1. Lysyl oxidase isoforms in gastric cancer.

    PubMed

    Añazco, Carolina; Delgado-López, Fernando; Araya, Paulina; González, Ileana; Morales, Erik; Pérez-Castro, Ramón; Romero, Jacqueline; Rojas, Armando

    2016-09-01

    Gastric cancer (GC) is the fifth most frequent cancer in the world and shows the highest incidence in Latin America and Asia. An increasing amount of evidence demonstrates that lysyl oxidase isoforms, a group of extracellular matrix crosslinking enzymes, should be considered as potential biomarkers and therapeutic targets in GC. In this review, we focus on the expression levels of lysyl oxidase isoforms, its functions and the clinical implications in GC. Finding novel proteins related to the processing of these extracellular matrix enzymes might be helpful in the design of new therapies, which, in combination with classic pharmacology, could be used to delay the progress of this aggressive cancer and offer a wider temporal window for clinical intervention. PMID:27564724

  2. Identification of Gastric Cancer Biomarkers Using 1H Nuclear Magnetic Resonance Spectrometry

    PubMed Central

    Yong, Wei Peng; Yeow, Chen Hua

    2016-01-01

    Existing gastric cancer diagnosing methods were invasive, hence, a reliable non-invasive gastric cancer diagnosing method is needed. As a starting point, we used 1H NMR for identifying gastric cancer biomarkers using a panel of gastric cancer spheroids and normal gastric spheroids. We were able to identify 8 chemical shift biomarkers for gastric cancer spheroids. Our data suggests that the cancerous and non-cancerous spheroids significantly differ in the lipid composition and energy metabolism. These results encourage the translation of these biomarkers into in-vivo gastric cancer detection methodology using MRI-MS. PMID:27611679

  3. Identification of Gastric Cancer Biomarkers Using 1H Nuclear Magnetic Resonance Spectrometry.

    PubMed

    Ramachandran, Gokula Krishnan; Yong, Wei Peng; Yeow, Chen Hua

    2016-01-01

    Existing gastric cancer diagnosing methods were invasive, hence, a reliable non-invasive gastric cancer diagnosing method is needed. As a starting point, we used 1H NMR for identifying gastric cancer biomarkers using a panel of gastric cancer spheroids and normal gastric spheroids. We were able to identify 8 chemical shift biomarkers for gastric cancer spheroids. Our data suggests that the cancerous and non-cancerous spheroids significantly differ in the lipid composition and energy metabolism. These results encourage the translation of these biomarkers into in-vivo gastric cancer detection methodology using MRI-MS. PMID:27611679

  4. The endoscopic diagnosis of early gastric cancer

    PubMed Central

    Yao, Kenshi

    2013-01-01

    The aim of this article is to demonstrate the basic principles for the endoscopic diagnosis of early gastric cancer. The diagnostic process can be divided into two steps, detection and characterization. Detection requires good endoscopic technique, and thorough knowledge. With regard to technique, we should administer the optimum preparation to patients, including an antiperistaltic agent. Furthermore, in order to map the entire stomach we need to follow a standardized protocol, and we propose a systematic screening protocol for the stomach. With regard to knowledge, we should be able to identify high-risk background mucosa, and we should be aware of the indicators of a suspicious lesion. Chromoendoscopy and magnifying endoscopy are promising image-enhanced endoscopic techniques for characterization. The proposed criteria for a cancerous lesion are as follows: conventional endoscopic findings of 1) a well-demarcated lesion and 2) irregularity in color/surface pattern; vessel plus surface classification using magnifying endoscopy with narrow-band imaging findings of 1) irregular microvascular pattern with a demarcation line or 2) irregular microsurface pattern with a demarcation line. Conventional endoscopy and subsequent image-enhanced endoscopy can both contribute to the detection of early gastric cancer. PMID:24714327

  5. Ramucirumab: A Review in Advanced Gastric Cancer.

    PubMed

    Greig, Sarah L; Keating, Gillian M

    2015-10-01

    Ramucirumab (Cyramza(®)), an intravenously administered, monoclonal antibody against vascular endothelial growth factor receptor-2, is approved in the USA, EU and Japan (either as a single agent or in combination with paclitaxel) as second-line treatment in adults with advanced gastric or gastro-oesophageal junction adenocarcinoma. In two phase III trials (REGARD and RAINBOW) in this indication, overall survival and progression-free survival were significantly prolonged with ramucirumab 8 mg/kg every 2 weeks compared with placebo, and with ramucirumab 8 mg/kg every 2 weeks plus weekly paclitaxel compared with placebo plus paclitaxel. Ramucirumab had a generally acceptable tolerability profile in phase III trials; hypertension was the most common non-haematological adverse event of grade 3 or higher with ramucirumab (either alone or with paclitaxel). As the first antiangiogenic agent to provide significant survival benefit in patients with advanced gastric cancer, ramucirumab is a valuable option in the second-line treatment of advanced gastric or gastro-oesophageal junction adenocarcinoma.

  6. Piperlongumine as a direct TrxR1 inhibitor with suppressive activity against gastric cancer.

    PubMed

    Zou, Peng; Xia, Yiqun; Ji, Jiansong; Chen, Weiqian; Zhang, Jinsan; Chen, Xi; Rajamanickam, Vinothkumar; Chen, Gaozhi; Wang, Zhe; Chen, Lingfeng; Wang, Yifeng; Yang, Shulin; Liang, Guang

    2016-05-28

    Piperlongumine (PL), a natural alkaloid isolated from the fruit of long pepper, is known to selectively kill tumor cells while sparing their normal counterparts. However, the cellular target and potent anticancer efficacy of PL in numerous types of human cancer cells have not been fully defined. We report here that PL may interact with the thioredoxin reductase 1 (TrxR1), an important selenocysteine (Sec)-containing antioxidant enzyme, to induce reactive oxygen species (ROS)-mediated apoptosis in human gastric cancer cells. By inhibiting TrxR1 activity and increasing intracellular ROS levels, PL induces a lethal endoplasmic reticulum stress and mitochondrial dysfunction in human gastric cancer cells. Importantly, knockdown of TrxR1 sensitizes cells to PL treatment, and PL displays synergistic lethality with GSH inhibitors (BSO and Erastin) against gastric cancer cells. In vivo, PL treatment markedly reduces the TrxR1 activity and tumor cell burden. Remarkably, TrxR1 was significantly overexpressed in gastric cancer cell lines and human gastric cancer tissues. Targeting TrxR1 with PL thus discloses a previously unrecognized mechanism underlying the biological activity of PL and provides an in-depth insight into the action of PL in the treatment of gastric cancer. PMID:26963494

  7. Rebamipide inhibits gastric cancer growth by targeting survivin and Aurora-B

    SciTech Connect

    Tarnawski, A.; E-mail: andrzej.tarnawski@med.va.gov; Pai, R.; Chiou, S.-K.; Chai, J.; Chu, E.C.

    2005-08-19

    Rebamipide accelerates healing of gastric ulcers and gastritis but its actions on gastric cancer are not known. Survivin, an anti-apoptosis protein, is overexpressed in stem, progenitor, and cancer cells. In gastric cancer, increased and sustained survivin expression provides survival advantage and facilitates tumor progression and resistance to anti-cancer drugs. Aurora-B kinase is essential for chromosome alignment and mitosis progression but surprisingly its role in gastric cancer has not been explored. We examined in human gastric cancer AGS cells: (1) survivin expression, (2) localization of survivin and Aurora-B (3) cell proliferation, and (4) effects of specific survivin siRNA and/or rebamipide (free radical scavenging drug) on survivin and Aurora-B expression and cell proliferation. Survivin and Aurora-B are strongly expressed in human AGS gastric cancer cells and co-localize during mitosis. Survivin siRNA significantly reduces AGS cell viability. Rebamipide significantly downregulates in AGS cell survivin expression, its association with Aurora-B and cell proliferation. Rebamipide-induced downregulation of survivin is at the transcription level and does not involve ubiquitin-proteasome pathway.

  8. Sentinel lymph node navigation surgery for gastric cancer: Does it really benefit the patient?

    PubMed Central

    Tani, Tohru; Sonoda, Hiromichi; Tani, Masaji

    2016-01-01

    Sentinel lymph node (SLN) navigation surgery is accepted as a standard treatment procedure for malignant melanoma and breast cancer. However, the benefit of reduced lymphadenectomy based on SLN examination remains unclear in cases of gastric cancer. Here, we review previous studies to determine whether SLN navigation surgery is beneficial for gastric cancer patients. Recently, a large-scale prospective study from the Japanese Society of Sentinel Node Navigation Surgery reported that the endoscopic dual tracer method, using a dye and radioisotope for SLN biopsy, was safe and effective when applied to cases of superficial and relatively small gastric cancers. SLN mapping with SLN basin dissection was preferred for early gastric cancer since it is minimally invasive. However, previous studies reported that limited gastrectomy and lymphadenectomy may not improve the patient’s postoperative quality of life (QOL). As a result, the benefit of SLN navigation surgery for gastric cancer patients, in terms of their QOL, is limited. Thus, endoscopic and laparoscopic limited gastrectomy combined with SLN navigation surgery has the potential to become the standard minimally invasive surgery in early gastric cancer. PMID:26973385

  9. Gastric Cancer in the Excluded Stomach 10 Years after Gastric Bypass

    PubMed Central

    Tinoco, Augusto; Gottardi, Lorena F.; Boechat, Eduardo D.

    2015-01-01

    According to the Brazilian health authorities, around 2,000 new cases of gastric cancer emerge in Brazil per year (Instituto Nacional de Câncer José Alencar Gomes da Silva, 2014). Indeed, gastric cancer constitutes the second most common cause of cancer-related mortality worldwide and 95% of such malignancies are adenocarcinomas (De Roover et al., 2006, and Clark et al., 2006). Roux-en-Y gastric bypass (RYGB) is a procedure frequently employed in bariatric surgery but restricted access to the excluded stomach means that discovery of gastric lesions is difficult, and diagnosis and treatment may be delayed. We report herein a case of gastric adenocarcinoma in the excluded stomach of a patient submitted to RYGB with the purpose of illustrating the difficulty of diagnosing and treating this rare condition. PMID:26229705

  10. Gastric cancer: The times they are a-changin’

    PubMed Central

    Satolli, Maria Antonietta; Buffoni, Lucio; Spadi, Rosella; Roato, Ilaria

    2015-01-01

    Gastric cancer is the third leading cause of cancer death worldwide. Even though during these last decades gastric cancer incidence decreased in Western countries, it remains endemic and with a high incidence in Eastern countries. The survival in advanced and metastatic stage of gastric cancer is still very poor. Recently the Cancer Genoma Atlas Research Network identified four subtypes with different molecular profiles to classify gastric cancer in order to offer the optimal targeted therapies for pre-selected patients. Indeed, the key point is still the selection of patients for the right treatment, on basis of molecular tumor characterization. Since chemotherapy reached a plateau of efficacy for gastric cancer, the combination between cytotoxic therapy and biological agents gets a better prognosis and decreases chemotherapeutic toxicity. Currently, Trastuzumab in combination with platinum and fluorouracil is the only approved targeted therapy in the first line for c-erbB2 positive patients, whereas Ramucirumab is the only approved targeted agent for patients with metastatic gastric cancer. New perspectives for an effective treatment derived from the immunotherapeutic strategies. Here, we report an overview on gastric cancer treatments, with particular attention to recent advances in targeted therapies and in immunotherapeutic approach. PMID:26600930

  11. Artesunate inhibits the growth and induces apoptosis of human gastric cancer cells by downregulating COX-2.

    PubMed

    Zhang, Ping; Luo, He-Sheng; Li, Ming; Tan, Shi-Yun

    2015-01-01

    Artesunate, a derivative of artemisinin isolated from Artemisia annua L., has been traditionally used to treat malaria, and artesunate has demonstrated cytotoxic effects against a variety of cancer cells. However, there is little available information about the antitumor effects of artesunate on human gastric cancer cells. In the present study, we investigated the antitumor effect of artesunate on human gastric cancer cells and whether its antitumor effect is associated with reduction in COX-2 expression. The effects of artesunate on the growth and apoptosis of gastric cancer cells were investigated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometric analysis of annexin V-fluorescein isothiocyanate/propidium iodide staining, rhodamine 123 staining, and Western blot analysis. Results indicate that artesunate exhibits antiproliferative effects and apoptosis-inducing activities. Artesunate markedly inhibited gastric cancer cell proliferation in a time- and dose-dependent manner and induced apoptosis in gastric cancer cells a dose-dependent manner, which was associated with a reduction in COX-2 expression. Treatment with the selective COX-2 inhibitor celecoxib, or transient transfection of gastric cancer cells with COX-2 siRNA, also inhibited cell proliferation and induced apoptosis. Furthermore, the treatment with artesunate promoted the expression of proapoptotic factor Bax and suppressed the expression of antiapoptotic factor Bcl-2. In addition, caspase-3 and caspase-9 were activated, and artesunate induced loss of mitochondrial membrane potential, suggesting that the apoptosis is mediated by mitochondrial pathways. These results demonstrate that artesunate has an effect on anti-gastric cancer cells. One of the antitumor mechanisms of artesunate may be that its inhibition of COX-2 led to reduced proliferation and induction of apoptosis, connected with mitochondrial dysfunction. Artesunate might be a potential therapeutic

  12. Differential expression of CCN family members CYR611, CTGF and NOV in gastric cancer and their association with disease progression

    PubMed Central

    Li, Jun; Gao, Xiangyu; Ji, Ke; Sanders, Andrew J.; Zhang, Zhongtao; Jiang, Wen G.; Ji, Jiafu; Ye, Lin

    2016-01-01

    CCN is an acronym for cysteine-rich protein 61 (CYR61), connective tissue growth factor (CTGF) and nephroblastoma overexpressed (NOV). Aberrations of certain CCN members including CYR61, CTGF, Wnt1-inducible signalling pathway protein (WISP)-1 and -3 have been reported in gastric cancer. The present study aimed to examine the clinical relevance of NOV along with CYR61 and CTGF in gastric cancer by analysing their transcript levels. CYR61, CTGF and NOV transcript expression in 324 gastric cancer samples with paired adjacent normal gastric tissues were determined using real-time quantitative PCR and the results were statistically analysed against patient clinicopathological data using SPSS software. NOV mRNA levels in gastric cancer tissues were significantly elevated when compared with levels in their paired adjacent non-cancerous tissues. Local advanced tumours with invasive expansion (T3 and T4) expressed higher levels of NOV (p=0.013) compared with the less invasive tumours (T1 and T2). CYR61 transcript levels were also significantly increased in gastric cancers compared with levels in the adjacent non-cancerous tissues. Kaplan-Meier survival curves revealed that patients with CYR61-low transcript levels had longer overall survival (OS) (p=0.018) and disease-free survival (DFS) (p=0.015). NOV overexpression promoted the in vitro proliferation of AGS cells while the knockdown resulted in a reduced proliferation of HGC27 cells. A similar effect was observed for the invasion of these two gastric cancer cell lines. NOV expression was increased in gastric cancer which was associated with local invasion and distant metastases. Taken together, the expression of NOV and CYR61 was increased in gastric cancer. The elevated expression of CYR61 was associated with poorer survival. NOV promoted proliferation and invasion of gastric cancer cells. Further investigations may highlight their predictive and therapeutic potential in gastric cancer. PMID:27633176

  13. Gastric cancer - clinical and epidemiological aspects.

    PubMed

    Venerito, Marino; Link, Alexander; Rokkas, Theodoros; Malfertheiner, Peter

    2016-09-01

    Gastric cancer (GC) ranks fifth for cancer incidence and second for cancer deaths. Epidemiological data showed that survivors of Hodgkin's lymphoma and patients with pernicious anemia etiologically linked to autoimmune gastritis are at increased risk of GC. Screening of patients with autoimmune thyroid disease by means of pepsinogen (PG) I and PG I/II detected autoimmune gastritis with oxyntic gastric atrophy in one of four patients and may be recommended for GC prevention purposes. The International Agency for Research on Cancer reported a positive association between consumption of processed meet and increased GC risk. A new GC risk prediction model based on biological markers, age, gender, smoking status, family history of GC, and consumption of highly salted food showed good predictive performance, and might prompt individuals to modify their lifestyle habits, attend regular check-up visits or participate in screening programs. A novel GC classification based on gene expression of primary resected cancers correlated with clinicopathological features. Noncoding RNA for GC screening remains the focus of multiple studies. Patients with early GC undergoing endoscopic resection are more likely to develop metachronous lesions than patients undergoing surgery and endoscopic surveillance is warranted in this special cohort. The addition of gastrectomy to chemotherapy did not improve survival of patients with advanced GC and a single noncurable factor. Apatinib, a novel oral vascular endothelial growth factor receptor 2 tyrosine kinase inhibitor, improved the median overall survival of patients with advanced GC and progressive disease after two or more lines of prior chemotherapy of nearly 3 months. PMID:27531538

  14. Biomarkers of Helicobacter pylori-associated gastric cancer

    PubMed Central

    Cooke, Cara L; Torres, Javier; Solnick, Jay V

    2013-01-01

    Helicobacter pylori-associated gastric cancer is a major cause of morbidity and mortality worldwide, and is predicted to become even more common in developing countries as the population ages. Since gastric cancer develops slowly over years to decades, and typically progresses though a series of well-defined histologic stages, cancer biomarkers have potential to identify asymptomatic individuals in whom surgery might be curative, or even those for whom antibiotics to eradicate H. pylori could prevent neoplastic transformation. Here we describe some of the challenges of biomarker discovery, summarize current approaches to biomarkers of gastric cancer, and explore some recent novel strategies. PMID:23851317

  15. Characteristics of gastric cancer in Asia

    PubMed Central

    Rahman, Rubayat; Asombang, Akwi W; Ibdah, Jamal A

    2014-01-01

    Gastric cancer (GC) is the fourth most common cancer in the world with more than 70% of cases occur in the developing world. More than 50% of cases occur in Eastern Asia. GC is the second leading cause of cancer death in both sexes worldwide. In Asia, GC is the third most common cancer after breast and lung and is the second most common cause of cancer death after lung cancer. Although the incidence and mortality rates are slowly declining in many countries of Asia, GC still remains a significant public health problem. The incidence and mortality varies according to the geographic area in Asia. These variations are closely related to the prevalence of GC risk factors; especially Helicobacter pylori (H. pylori) and its molecular virulent characteristics. The gradual and consistent improvements in socioeconomic conditions in Asia have lowered the H. pylori seroprevalence rates leading to a reduction in the GC incidence. However, GC remains a significant public health and an economic burden in Asia. There has been no recent systemic review of GC incidence, mortality, and H. pylori molecular epidemiology in Asia. The aim of this report is to review the GC incidence, mortality, and linkage to H. pylori in Asia. PMID:24782601

  16. ZnRF3 Induces Apoptosis of Gastric Cancer Cells by Antagonizing Wnt and Hedgehog Signaling.

    PubMed

    Qin, Hongzhen; Cai, Aizhen; Xi, Hongqing; Yuan, Jing; Chen, Lin

    2015-11-01

    A large proportion of malignant cancers of the stomach are gastric adenocarcinoma type. In spite of many studies, the molecular basis for this cancer is still unclear. Deregulated cell proliferative signaling via Wnt/β-catenin and Hedgehog pathways is considered important in the pathogenesis of many cancers including the gastric cancer. Recent studies identified ZnRF3 protein, which is a E3-ubiquitin ligase and which is either deleted or mutated in cancers, to inhibit Wnt signaling. However, the significance of ZnRF3 in the control of gastric cancer and whether it also regulates Hedgehog signaling pathway, is not known. In the present study, we assessed the expression of ZnRF3 in gastric tumors and paracancerous tissues from 58 patients (44 male and 14 female) of different ages and related this to patient survival. We observed a clear relationship between ZnRF3 expression in paracancerous tissue and tumor size. Also, ZnRF3 expression was much higher in tumors from aged patients. Male patients showed higher mortality than the females. Mechanistic studies using normal gastric cells (GES1) and gastric cancer cells (MGC-803) infected with either AdZnRF3 or AdGFP viral vectors, revealed that ZnRF3 overexpression causes significantly more apoptosis and lowered proliferation of cancer cells. ZnRF3 overexpression led to greatly reduced levels of Lgr5, a component of Wnt signaling and also Gli1, a component of Hedgehog signaling. Thus, ZnRF3 negatively influences both the Wnt and Hedgehog proliferative pathways, and probably this way it negatively regulates cancer progression. These results suggest the importance of normal ZnRF3 function in checking the progression of cancer cell growth and indicate that a lack of this protein can lead to poorer clinical outcomes for gastric cancer patients. PMID:27352324

  17. [Current standards in the treatment of gastric cancer].

    PubMed

    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.

  18. The Traditional Chinese Medicine Baicalein Potently Inhibits Gastric Cancer Cells

    PubMed Central

    Mu, Jiasheng; Liu, Tianrun; Jiang, Lin; Wu, Xiangsong; Cao, Yang; Li, Maolan; Dong, Qian; Liu, Yingbin; Xu, Haineng

    2016-01-01

    Baicalein, a traditional Chinese medicine, is a member of the flavone subclass of flavonoids. It has been reported to have anticancer activities in several human cancer cell lines in vitro. However, the therapeutic effects of baicalein on human gastric cancer and the mechanisms of action of baicalein have not been extensively studied. In the present study, we utilized a cell viability assay and an in vivo tumor growth assay to test the inhibitory effects of baicalein on gastric cancer. Analyses of the cell cycle, apoptosis and alterations in protein levels were performed to elucidate how baicalein functions in gastric cancer. We found that baicalein could potently inhibit gastric cancer cell growth and colony formation. Baicalein robustly induced arrest at the S phase in the gastric cancer cell line SGC-7901. It induced SGC-7901 cell apoptosis and disrupted the mitochondrial membrane potential (ΔΨm) in a dose-dependent manner. Analysis of protein expression levels in SGC-7901 cells showed downregulation of Bcl-2 and upregulation of Bax in response to baicalein treatment. These results indicate that baicalein induces apoptosis of gastric cancer cells through the mitochondrial pathway. In an in vivo subcutaneous xenograft model, baicalein exhibited excellent tumor inhibitory effects. These results indicate that baicalein may be a potential drug for gastric cancer therapy. PMID:26918059

  19. The Traditional Chinese Medicine Baicalein Potently Inhibits Gastric Cancer Cells.

    PubMed

    Mu, Jiasheng; Liu, Tianrun; Jiang, Lin; Wu, Xiangsong; Cao, Yang; Li, Maolan; Dong, Qian; Liu, Yingbin; Xu, Haineng

    2016-01-01

    Baicalein, a traditional Chinese medicine, is a member of the flavone subclass of flavonoids. It has been reported to have anticancer activities in several human cancer cell lines in vitro. However, the therapeutic effects of baicalein on human gastric cancer and the mechanisms of action of baicalein have not been extensively studied. In the present study, we utilized a cell viability assay and an in vivo tumor growth assay to test the inhibitory effects of baicalein on gastric cancer. Analyses of the cell cycle, apoptosis and alterations in protein levels were performed to elucidate how baicalein functions in gastric cancer. We found that baicalein could potently inhibit gastric cancer cell growth and colony formation. Baicalein robustly induced arrest at the S phase in the gastric cancer cell line SGC-7901. It induced SGC-7901 cell apoptosis and disrupted the mitochondrial membrane potential (ΔΨm) in a dose-dependent manner. Analysis of protein expression levels in SGC-7901 cells showed downregulation of Bcl-2 and upregulation of Bax in response to baicalein treatment. These results indicate that baicalein induces apoptosis of gastric cancer cells through the mitochondrial pathway. In an in vivo subcutaneous xenograft model, baicalein exhibited excellent tumor inhibitory effects. These results indicate that baicalein may be a potential drug for gastric cancer therapy.

  20. Detection of microsatellite instability in gastric cancer and dysplasia tissues

    PubMed Central

    Li, Bing; Liu, Hong-Yi; Guo, Shao-Hua; Sun, Peng; Gong, Fang-Ming; Jia, Bao-Qing

    2015-01-01

    Objective: We aimed to investigate the association between gastric cancer and microsatellite instability (MSI) in the present study. Method: Phenol-chloroform method was employed for DNA extraction from the cancer tissues of 65gastric cancer patients and the dysplasia tissues and normal control tissues of 32 non-gastric cancer patients. The microsatellite loci Bat25, Bat26, D2S123, D5S346 and D17S250 were detected by using PCR-SSCP silver staining technique, and the MSI of the gastric cancer tissues and the precancerous tissues was analyzed. Results: Of 65 gastric cancer cases, MSI was detected in 43 cases, with the detection rate of 66.2%. There were 13 cases showing MSI-H and 30 cases showing MSI-L, accounting for 30.2% and 69.8%, respectively. Among 32 cases of dysplasia tissues, MSI was detected in 10 cases, with the detection rate of 31.3%. Two cases of dysplasia tissues showed MSI-H and 8 cases showed MSI-L, accounting for 20.0% and 80.0%, respectively. Conclusion: Gastric cancer patients had a high detection rate of MSI. It is speculated that MSI is another molecular mechanism of carcinogenesis and may serve as a sensitive diagnostic indicator of gastric cancer. PMID:26885089

  1. Gastric hyperplastic polyps coexisting with early gastric cancers, adenoma and neuroendocrine cell hyperplasia.

    PubMed

    Karpińska-Kaczmarczyk, K; Lewandowska, M; Białek, A; Ławniczak, M; Urasińska, E

    2016-03-01

    Gastric hyperplastic polyps (GHP) constitute up to 93% of all benign epithelial polyps of the stomach. The average probability of malignant transformation in GHP is 0.6-22% in large series. The aim of the study was to present the coexistence of GHP with early gastric cancer (EGC), gastric adenoma (GA), neuroendocrine cell hyperplasia (NH) and well-differentiated neuroendocrine tumour (NET G1). Three cases were studied to reveal clinical data and morphological changes and to assess the relationship between GHP and accompanying gastric neoplastic lesions. PMID:27179272

  2. Diet and the risk of gastric cancer: review of epidemiological evidence.

    PubMed

    Tsugane, Shoichiro; Sasazuki, Shizuka

    2007-01-01

    There are geographic and ethnic differences in the incidence of gastric cancer around the world as well as with its trends for each population over time. The incidence patterns observed among immigrants change according to where they live. All of these factors serve to indicate the close association of gastric cancer with modifiable factors such as diet. This review presents epidemiological evidence on the association between dietary factors and gastric cancer based on previous systematic reviews and subsequent updates. Infection with Helicobacter pylori is a strong and established risk factor of gastric cancer but is not a sufficient cause for its development. Substantial evidence from ecological, case-control, and cohort studies strongly suggests that the risk may be increased with a high intake of various traditional salt-preserved foods and salt per se and decreased with a high intake of fruit and vegetables, particularly fruit. However, it remains unclear which constituents in fruit and vegetables play a significant role in gastric cancer prevention. Among them, vitamin C is a plausible candidate supported by a relatively large body of epidemiological evidence. Consumption of green tea is possibly associated with a decreased risk of gastric cancer, although the protective effects have been, for the most part, identified in Japanese women, most of whom are nonsmokers. In contrast, processed meat and N-nitroso compounds may be positively associated with the risk of gastric cancer. In conclusion, dietary modification by reducing salt and salted food intake, as well as by increasing intake of fruit and vitamin C, represents a practical strategy to prevent gastric cancer. PMID:17577615

  3. Molecular Classification of Gastric Cancer: A new paradigm

    PubMed Central

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

    2011-01-01

    Purpose Gastric cancer may be subdivided into three 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. Experimental Design Patients with localized gastric adenocarcinoma being screened for a phase II preoperative clinical trial (NCI 5917) underwent endoscopic biopsy for fresh tumor procurement. 4–6 targeted biopsies of the primary tumor were obtained. Macrodissection was performed to ensure >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. Results 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 three gastric cancer subtypes, successfully classifying each into tightly grouped clusters. Leave-one-out cross validation error was 0.14, suggesting that >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. Conclusions Subtypes of gastric cancer that have epidemiologic and histologic distinction 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. PMID:21430069

  4. Helicobacter pylori Eradication for Prevention of Metachronous Recurrence after Endoscopic Resection of Early Gastric Cancer.

    PubMed

    Bang, Chang Seok; Baik, Gwang Ho; Shin, In Soo; Kim, Jin Bong; Suk, Ki Tae; Yoon, Jai Hoon; Kim, Yeon Soo; Kim, Dong Joon

    2015-06-01

    Controversies persist regarding the effect of Helicobacter pylori eradication on the development of metachronous gastric cancer after endoscopic resection of early gastric cancer (EGC). The aim of this study was to assess the efficacy of Helicobacter pylori eradication after endoscopic resection of EGC for the prevention of metachronous gastric cancer. A systematic literature review and meta-analysis were conducted using the core databases PubMed, EMBASE, and the Cochrane Library. The rates of development of metachronous gastric cancer between the Helicobacter pylori eradication group vs. the non-eradication group were extracted and analyzed using risk ratios (RRs). A random effect model was applied. The methodological quality of the enrolled studies was assessed by the Risk of Bias table and by the Newcastle-Ottawa Scale. Publication bias was evaluated through the funnel plot with trim and fill method, Egger's test, and by the rank correlation test. Ten studies (2 randomized and 8 non-randomized/5,914 patients with EGC or dysplasia) were identified and analyzed. Overall, the Helicobacter pylori eradication group showed a RR of 0.467 (95% CI: 0.362-0.602, P < 0.001) for the development of metachronous gastric cancer after endoscopic resection of EGC. Subgroup analyses showed consistent results. Publication bias was not detected. Helicobacter pylori eradication after endoscopic resection of EGC reduces the occurrence of metachronous gastric cancer.

  5. The Mechanism in Gastric Cancer Chemoprevention by Allicin.

    PubMed

    Luo, Runlan; Fang, Dengyang; Hang, Hongdong; Tang, Zeyao

    2016-01-01

    Gastric cancer remains high prevalence and fatality rates in China even though its morbidity has been decreased drastically. Allicin, which is from an assistance food-garlic (Allium Sativum L), was found to be effective in gastric cancer treatment. It is a defensive substance with a board biological properties: inhibition of bacteria, fungus, virus, controlled hypertension, diabetes, and chemoprevention of several cancers, etc. Experiments have shown that allicin can be chemopreventive to gastric cancer by inhibiting the growth of cancer cells, arresting cell cycle at G2/M phase, endoplasmic reticulum (ER) stress, and mitochondria-mediated apoptosis, which includes the caspase-dependent/-independent pathways and death receptor pathway. Those mechanisms probably involve in modulating enzymatic activity, restraining DNA formation, scavenging free radicals, and affecting cell proliferation and even tumor growth. Therefore, this review is focus on the mechanism of allicin in gastric cancer. PMID:26555611

  6. Surgical management of advanced gastric cancer: An evolving issue.

    PubMed

    Marano, L; Polom, K; Patriti, A; Roviello, G; Falco, G; Stracqualursi, A; De Luca, R; Petrioli, R; Martinotti, M; Generali, D; Marrelli, D; Di Martino, N; Roviello, F

    2016-01-01

    Worldwide, gastric cancer represents the fifth most common cancer and the third leading cause of cancer deaths. Although the overall 5-year survival for resectable disease was more than 70% in Japan due to the implementation of screening programs resulting in detection of disease at earlier stages, in Western countries more than two thirds of gastric cancers are usually diagnosed in advanced stages reporting a 5-year survival rate of only 25.7%. Anyway surgical resection with extended lymph node dissection remains the only curative therapy for non-metastatic advanced gastric cancer, while neoadjuvant and adjuvant chemotherapies can improve the outcomes aimed at the reduction of recurrence and extension of survival. High-quality research and advances in technologies have contributed to well define the oncological outcomes and have stimulated many clinical studies testing multimodality managements in the advanced disease setting. This review article aims to outline and discuss open issues in current surgical management of advanced gastric cancer. PMID:26632080

  7. Companion diagnostics for the targeted therapy of gastric cancer.

    PubMed

    Yoo, Changhoon; Park, Young Soo

    2015-10-21

    Gastric cancer is the fourth most common type of cancer and represents a major cause of cancer-related deaths worldwide. With recent biomedical advances in our understanding of the molecular characteristics of gastric cancer, many genetic alterations have been identified as potential targets for its treatment. Multiple novel agents are currently under development as the demand for active agents that improve the survival of gastric cancer patients constantly increases. Based on lessons from previous trials of targeted agents, it is now widely accepted that the establishment of an optimal diagnostic test to select molecularly defined patients is of equal importance to the development of active agents against targetable genetic alterations. Herein, we highlight the current status and future perspectives of companion diagnostics in the treatment of gastric cancer.

  8. Endoscopic surveillance of gastric cancers after Helicobacter pylori eradication.

    PubMed

    Kobayashi, Masaaki; Sato, Yuichi; Terai, Shuji

    2015-10-01

    The incidence and mortality of gastric cancer remains high in East Asian countries. Current data suggest that Helicobacter pylori (H. pylori) eradication might be more effective for preventing gastric cancer in young people before they develop atrophic gastritis and intestinal metaplasia. However, the long-term effect of H. pylori eradication on metachronous cancer prevention after endoscopic resection (ER) of early gastric cancer remains controversial, with some discordance between results published for Japanese and Korean studies. The detection ability of synchronous lesions before ER and eradication of H. pylori directly influences these results. After eradication, some gastric cancers are more difficult to diagnose by endoscopy because of morphologic changes that lead to a flat or depressed appearance. Narrow-band imaging with magnifying endoscopy (NBI-ME) is expected to be useful for identifying metachronous cancers. However, some gastric cancers after eradication show a "gastritis-like" appearance under NBI-ME. The gastritis-like appearance correlates with the histological surface differentiation of the cancer tubules and superficial non-neoplastic epithelium atop or interspersed with the cancer. Till date, it remains unclear whether H. pylori eradication could prevent progression of gastric cancer. Until we can establish more useful endoscopic examination methodologies, regular endoscopic surveillance of high-risk groups is expected to be the most beneficial approach for detection.

  9. Endoscopic surveillance of gastric cancers after Helicobacter pylori eradication

    PubMed Central

    Kobayashi, Masaaki; Sato, Yuichi; Terai, Shuji

    2015-01-01

    The incidence and mortality of gastric cancer remains high in East Asian countries. Current data suggest that Helicobacter pylori (H. pylori) eradication might be more effective for preventing gastric cancer in young people before they develop atrophic gastritis and intestinal metaplasia. However, the long-term effect of H. pylori eradication on metachronous cancer prevention after endoscopic resection (ER) of early gastric cancer remains controversial, with some discordance between results published for Japanese and Korean studies. The detection ability of synchronous lesions before ER and eradication of H. pylori directly influences these results. After eradication, some gastric cancers are more difficult to diagnose by endoscopy because of morphologic changes that lead to a flat or depressed appearance. Narrow-band imaging with magnifying endoscopy (NBI-ME) is expected to be useful for identifying metachronous cancers. However, some gastric cancers after eradication show a “gastritis-like” appearance under NBI-ME. The gastritis-like appearance correlates with the histological surface differentiation of the cancer tubules and superficial non-neoplastic epithelium atop or interspersed with the cancer. Till date, it remains unclear whether H. pylori eradication could prevent progression of gastric cancer. Until we can establish more useful endoscopic examination methodologies, regular endoscopic surveillance of high-risk groups is expected to be the most beneficial approach for detection. PMID:26457015

  10. The stem cell factor SOX2 regulates the tumorigenic potential in human gastric cancer cells.

    PubMed

    Hütz, Katharina; Mejías-Luque, Raquel; Farsakova, Katarina; Ogris, Manfred; Krebs, Stefan; Anton, Martina; Vieth, Michael; Schüller, Ulrich; Schneider, Marlon R; Blum, Helmut; Wagner, Ernst; Jung, Andreas; Gerhard, Markus

    2014-04-01

    Gastric cancer (GC) is still one of the most common causes of cancer-related death worldwide, which is mainly attributable to late diagnosis and poor treatment options. Infection with Helicobacter pylori, different environmental factors and genetic alterations are known to influence the risk of developing gastric tumors. However, the molecular mechanisms involved in gastric carcinogenesis are still not fully understood, making it difficult to design targeted therapeutic approaches. Aberrant expression of the specific gastric differentiation marker SOX2 has been observed in stomach cancer. However, the role of SOX2 in gastric tumors has not been well established to date. To elucidate the role of SOX2 in gastric tumorigenesis, SOX2 transcriptional activity was blocked in AZ-521 cells. Interestingly, inhibition of SOX2 reduced cell proliferation and migration, increased apoptosis and induced changes in cell cycle. Blocking of SOX2 also reduced the tumorigenic potential of AZ-521 cells in vivo. In addition, correlation of SOX2 expression and proliferation was observed in a subset of human gastric tumors. Finally, target genes of SOX2 were for the first time identified by RNA microarray in GC cells. Taken together, the results presented here indicate that SOX2 controls several aspects related to GC development and progression by regulating the expression of members of important signaling pathways. These findings could provide new therapeutic options for a subset of GCs exhibiting SOX2 deregulation.

  11. Prediction Model for Gastric Cancer Incidence in Korean Population

    PubMed Central

    Kim, Sohee; Shin, Aesun; Yang, Hye-Ryung; Park, Junghyun; Choi, Il Ju; Kim, Young-Woo; Kim, Jeongseon; Nam, Byung-Ho

    2015-01-01

    Background Predicting high risk groups for gastric cancer and motivating these groups to receive regular checkups is required for the early detection of gastric cancer. The aim of this study is was to develop a prediction model for gastric cancer incidence based on a large population-based cohort in Korea. Method Based on the National Health Insurance Corporation data, we analyzed 10 major risk factors for gastric cancer. The Cox proportional hazards model was used to develop gender specific prediction models for gastric cancer development, and the performance of the developed model in terms of discrimination and calibration was also validated using an independent cohort. Discrimination ability was evaluated using Harrell’s C-statistics, and the calibration was evaluated using a calibration plot and slope. Results During a median of 11.4 years of follow-up, 19,465 (1.4%) and 5,579 (0.7%) newly developed gastric cancer cases were observed among 1,372,424 men and 804,077 women, respectively. The prediction models included age, BMI, family history, meal regularity, salt preference, alcohol consumption, smoking and physical activity for men, and age, BMI, family history, salt preference, alcohol consumption, and smoking for women. This prediction model showed good accuracy and predictability in both the developing and validation cohorts (C-statistics: 0.764 for men, 0.706 for women). Conclusions In this study, a prediction model for gastric cancer incidence was developed that displayed a good performance. PMID:26186332

  12. History of Helicobacter pylori, duodenal ulcer, gastric ulcer and gastric cancer

    PubMed Central

    Graham, David Y

    2014-01-01

    Helicobacter pylori (H. pylori) infection underlies gastric ulcer disease, gastric cancer and duodenal ulcer disease. The disease expression reflects the pattern and extent of gastritis/gastric atrophy (i.e., duodenal ulcer with non-atrophic and gastric ulcer and gastric cancer with atrophic gastritis). Gastric and duodenal ulcers and gastric cancer have been known for thousands of years. Ulcers are generally non-fatal and until the 20th century were difficult to diagnose. However, the presence and pattern of gastritis in past civilizations can be deduced based on the diseases present. It has been suggested that gastric ulcer and duodenal ulcer both arose or became more frequent in Europe in the 19th century. Here, we show that gastric cancer and gastric ulcer were present throughout the 17th to 19th centuries consistent with atrophic gastritis being the predominant pattern, as it proved to be when it could be examined directly in the late 19th century. The environment before the 20th century favored acquisition of H. pylori infection and atrophic gastritis (e.g., poor sanitation and standards of living, seasonal diets poor in fresh fruits and vegetables, especially in winter, vitamin deficiencies, and frequent febrile infections in childhood). The latter part of the 19th century saw improvements in standards of living, sanitation, and diets with a corresponding decrease in rate of development of atrophic gastritis allowing duodenal ulcers to become more prominent. In the early 20th century physician’s believed they could diagnose ulcers clinically and that the diagnosis required hospitalization for “surgical disease” or for “Sippy” diets. We show that while H. pylori remained common and virulent in Europe and the United States, environmental changes resulted in changes of the pattern of gastritis producing a change in the manifestations of H. pylori infections and subsequently to a rapid decline in transmission and a rapid decline in all H. pylori

  13. History of Helicobacter pylori, duodenal ulcer, gastric ulcer and gastric cancer.

    PubMed

    Graham, David Y

    2014-05-14

    Helicobacter pylori (H. pylori) infection underlies gastric ulcer disease, gastric cancer and duodenal ulcer disease. The disease expression reflects the pattern and extent of gastritis/gastric atrophy (i.e., duodenal ulcer with non-atrophic and gastric ulcer and gastric cancer with atrophic gastritis). Gastric and duodenal ulcers and gastric cancer have been known for thousands of years. Ulcers are generally non-fatal and until the 20th century were difficult to diagnose. However, the presence and pattern of gastritis in past civilizations can be deduced based on the diseases present. It has been suggested that gastric ulcer and duodenal ulcer both arose or became more frequent in Europe in the 19th century. Here, we show that gastric cancer and gastric ulcer were present throughout the 17th to 19th centuries consistent with atrophic gastritis being the predominant pattern, as it proved to be when it could be examined directly in the late 19th century. The environment before the 20th century favored acquisition of H. pylori infection and atrophic gastritis (e.g., poor sanitation and standards of living, seasonal diets poor in fresh fruits and vegetables, especially in winter, vitamin deficiencies, and frequent febrile infections in childhood). The latter part of the 19th century saw improvements in standards of living, sanitation, and diets with a corresponding decrease in rate of development of atrophic gastritis allowing duodenal ulcers to become more prominent. In the early 20th century physician's believed they could diagnose ulcers clinically and that the diagnosis required hospitalization for "surgical disease" or for "Sippy" diets. We show that while H. pylori remained common and virulent in Europe and the United States, environmental changes resulted in changes of the pattern of gastritis producing a change in the manifestations of H. pylori infections and subsequently to a rapid decline in transmission and a rapid decline in all H. pylori-related diseases.

  14. CMTM3 inhibits cell migration and invasion and correlates with favorable prognosis in gastric cancer

    PubMed Central

    Su, Yu; Lin, Yi; Zhang, Lianhai; Liu, Baocai; Yuan, Wanqiong; Mo, Xiaoning; Wang, Xiaohong; Li, Henan; Xing, Xiaofang; Cheng, Xiaojing; Dong, Bin; Hu, Ying; Du, Hong; Zhu, Yubing; Ding, Ning; Li, Jiyou; Liu, Weili; Ma, Yongzhen; Qiu, Xiaoyan; Ji, Jiafu; Han, Wenling

    2014-01-01

    The CKLF-like MARVEL transmembrane domain containing 3 (CMTM3) gene is a novel tumor suppressor with frequent epigenetic inactivation. In this study, we showed the role played by CMTM3 in gastric cancer cells as a tumor suppressor gene, and examined the correlation between CMTM3 expression and clinicopathological parameters using immunohistochemistry in gastric cancer patients with different pathological stages (n = 350). We found that CMTM3 expression was reduced or silenced by epigenetic regulation in gastric cell lines, and dramatically downregulated in primary gastric cancer tissues. Restoration of CMTM3 significantly affected migration and invasion of AGS and SGC-7901 cells (P < 0.001). In vivo experiments showed that peritoneal disseminated metastases were significantly suppressed by CMTM3 (P < 0.001). We further showed that the expression of MMP2 and the phosphorylation of Erk1/2 were decreased when CMTM3 was restored. In addition, by immunohistochemical staining, we found that the expression of CMTM3 was remarkably weaker in gastric cancer tissues than in normal mucosae (P = 0.008), and was significantly correlated with gender (P = 0.033), tumor depth (P = 0.049), stage (P = 0.021), and histological grade (P = 0.022). More importantly, CMTM3 expression was associated with prognosis in gastric cancer patients (P = 0.041), and was a significant independent prognostic indicator (hazard ratio = 0.704, 95% confidence interval, 0.498–0.994; P = 0.046). Our findings indicate that CMTM3 regulates migration and invasion of gastric cancer cells. Moreover, CMTM3 is a candidate marker for prognosis of gastric cancer in the clinic. PMID:24131472

  15. Early Gastric Cancer: Current Advances of Endoscopic Diagnosis and Treatment.

    PubMed

    Zhu, Linlin; Qin, Jinyu; Wang, Jin; Guo, Tianjiao; Wang, Zijing; Yang, Jinlin

    2016-01-01

    Endoscopy is a major method for early gastric cancer screening because of its high detection rate, but its diagnostic accuracy depends heavily on the availability of endoscopic instruments. Many novel endoscopic techniques have been shown to increase the diagnostic yield of early gastric cancer. With the improved detection rate of EGC, the endoscopic treatment has become widespread due to advances in the instruments available and endoscopist's experience. The aim of this review is to summarize frequently-used endoscopic diagnosis and treatment in early gastric cancer (EGC). PMID:26884753

  16. Gastric cancer: diagnosis, risk factors, treatment and life issues.

    PubMed

    Hicks, S

    Gastric cancer is the sixth most common malignancy in the UK. It is responsible for over 9000 deaths annually in the UK. Distal gastric cancer has a decreasing incidence, but proximal gastric cancer continues to increase. Gastroscopy remains the gold standards for accurate diagnosis. Early diagnosis is essential, but symptoms and signs are often mistaken for other less serious diseases. Major surgery is the only proven treatment, but 5-year survival rates postoperatively are only 34%, and many people will continue to suffer side-effects of the surgery. Open access gastroscopy and health promotion may be the best chance of detecting this disease early enough so that it is treated successfully.

  17. Gastric Cancer with Peritoneal Tuberculosis: Challenges in Diagnosis and Treatment

    PubMed Central

    Alshahrani, Amer Saeed

    2016-01-01

    Herein, we report a 39-year-old female patient presenting with gastric cancer and tuberculous peritonitis. The differential diagnosis between advanced gastric cancer with peritoneal carcinomatosis and early gastric cancer with peritoneal tuberculosis (TB), and the treatment of these two diseases, were challenging in this case. Physicians should have a high index of suspicion for peritoneal TB if the patient has a history of this disease, especially in areas with a high incidence of TB, such as South Korea. An early diagnosis is critical for patient management and prognosis. A surgical approach including tissue biopsy or laparoscopic exploration is recommended to confirm the diagnosis. PMID:27433397

  18. Effects of IL-10 haplotype and atomic bomb radiation exposure on gastric cancer risk.

    PubMed

    Hayashi, Tomonori; Ito, Reiko; Cologne, John; Maki, Mayumi; Morishita, Yukari; Nagamura, Hiroko; Sasaki, Keiko; Hayashi, Ikue; Imai, Kazue; Yoshida, Kengo; Kajimura, Junko; Kyoizumi, Seishi; Kusunoki, Yoichiro; Ohishi, Waka; Fujiwara, Saeko; Akahoshi, Masazumi; Nakachi, Kei

    2013-07-01

    Gastric cancer (GC) is one of the cancers that reveal increased risk of mortality and incidence in atomic bomb survivors. The incidence of gastric cancer in the Life Span Study cohort of the Radiation Effects Research Foundation (RERF) increased with radiation dose (gender-averaged excess relative risk per Gy = 0.28) and remains high more than 65 years after exposure. To assess a possible role of gene-environment interaction, we examined the dose response for gastric cancer incidence based on immunosuppression-related IL-10 genotype, in a cohort study with 200 cancer cases (93 intestinal, 96 diffuse and 11 other types) among 4,690 atomic bomb survivors participating in an immunological substudy. Using a single haplotype block composed of four haplotype-tagging SNPs (comprising the major haplotype allele IL-10-ATTA and the minor haplotype allele IL-10-GGCG, which are categorized by IL-10 polymorphisms at -819A>G and -592T>G, +1177T>C and +1589A>G), multiplicative and additive models for joint effects of radiation and this IL-10 haplotyping were examined. The IL-10 minor haplotype allele(s) was a risk factor for intestinal type gastric cancer but not for diffuse type gastric cancer. Radiation was not associated with intestinal type gastric cancer. In diffuse type gastric cancer, the haplotype-specific excess relative risk (ERR) for radiation was statistically significant only in the major homozygote category of IL-10 (ERR = 0.46/Gy, P = 0.037), whereas estimated ERR for radiation with the minor IL-10 homozygotes was close to 0 and nonsignificant. Thus, the minor IL-10 haplotype might act to reduce the radiation related risk of diffuse-type gastric cancer. The results suggest that this IL-10 haplotyping might be involved in development of radiation-associated gastric cancer of the diffuse type, and that IL-10 haplotypes may explain individual differences in the radiation-related risk of gastric cancer. PMID:23772925

  19. Role of Helicobacter pylori in gastric cancer: advances and controversies.

    PubMed

    Meng, Wenbo; Bai, Bing; Sheng, Liang; Li, Yan; Yue, Ping; Li, Xun; Qiao, Liang

    2015-11-01

    Gastric cancer is one of the most common cancers of digestive system globally and Helicobacter pylori (HP) infection is believed to be a major risk factor. HP can be classified into different types based on the presence and expression level of CagA and VacA, and, when exposed to adverse environment, HP changes its phenotype from helical type to coccoid type, with each having different pathogenicity. The mechanisms of HP-induced gastric carcinogenesis and progression are complicated, including DNA nitration and oxidation induced by mutagenic factors, HP-induced epigenetic modifications, HP-induced disruption of the balance between cell proliferation and apoptosis, and HP-induced cancer cell invasion and metastasis. HP may also affect the biological function of cancer stem cells and induction of cell autophagy. The lipopolysaccharide produced by HP can act through toll-like receptor-4 (TLR-4) to induce gastric mucosal inflammation and is thereby linked to the development of gastric cancer.

  20. Abnormal Growth Factor/Cytokine Network in Gastric Cancer

    PubMed Central

    2008-01-01

    Gastric cancer cells express a broad spectrum of the growth factor/cytokine receptor systems that organize the complex interaction between cancer cells and stromal cells in tumor microenvironment, which confers cell growth, apoptosis, morphogenesis, angiogenesis, progression and metastasis. However, these abnormal growth factor/cytokine networks differ in the two histological types of gastric cancer. Importantly, activation of nuclear factor-kB pathway by Helicobacter pylori infection may act as a key player for induction of growth factor/cytokine networks in gastritis and pathogenesis of gastric cancer. Better understanding of these events will no doubt provide new approaches for biomarkers of diagnosis and effective therapeutic targeting of gastric cancer. PMID:19308687

  1. Gastric Metastasis of Breast Cancer: A Case Series

    PubMed Central

    dos Santos Fernandes, Gustavo; Batista Bugiato Faria, Luiza D.; de Assis Pereira, Isadora; Neves, Natália C. Moreira; Vieira, Yasmine Oliveira; Leal, Alessandro I. Cavalcanti

    2016-01-01

    Gastric metastasis is rare but it can be the initial symptom of cancer. The second leading cause of this type of metastasis is breast cancer. A lack of clinical signs and nonspecific side effects of the treatment of primary tumors can lead to the misdiagnosis of metastatic gastric cancer. Upper gastrointestinal endoscopy with biopsy and immunohistochemistry should be used for diagnosis. Treatment is palliative; it includes chemo, endocrine, and radiation therapies. Four patients with breast cancer and gastric metastasis were identified. All the patients tested positive for estrogen and progesterone receptors, and received chemotherapy and hormone therapy. One patient underwent surgery and two received radiation therapy. Patients with breast cancer and gastrointestinal symptoms should be investigated for gastric metastasis, given its morbidity and negative impact on quality of life. PMID:27746881

  2. A Possible Link between Gastric Mucosal Atrophy and Gastric Cancer after Helicobacter pylori Eradication

    PubMed Central

    Tahara, Tomomitsu; Shibata, Tomoyuki; Horiguchi, Noriyuki; Kawamura, Tomohiko; Okubo, Masaaki; Ishizuka, Takamitsu; Nagasaka, Mitsuo; Nakagawa, Yoshihito; Ohmiya, Naoki

    2016-01-01

    Background The effect of H. pylori eradication in gastric cancer prevention can be attributed to the improvement of atrophic gastritis, which is a known risk of gastric cancer. However, gastric cancer has also been diagnosed after long-term H. pylori eradication. This study aimed to clarify the association between gastric atrophy and gastric cancer after H. pylori eradication, including its clinicopathological features. Methods A total of 55 consecutive patients with 64 early gastric cancers (EGCs) diagnosed after H. pylori eradication were enrolled. The degree of endoscopic atrophy and the histological degrees of mononuclear cell infiltration, atrophy, and metaplasia in the corpus and adjacent mucosa of the EGCs were determined and scored. Results The majority of EGCs (63/64) were located within the endoscopically assessed atrophic mucosa or along the atrophic border. The adjacent mucosa of the EGCs presented significantly higher degrees of all histological parameters than in the corpus (mononuclear cell infiltration, 0.86+/-0.09 vs. 0.51+/-0.11, P = 0.016; atrophy, 1.77+/-0.13 vs. 0.65+/-0.14, P<0.0001; metaplasia, 1.68+/-0.13 vs. 0.48+/-0.1, P<0.0001). The degree of endoscopic atrophy improved in the patients with longer post-H. pylori eradication periods; however, this trend was not observed for the histological parameters, and high degrees of atrophy and metaplasia were observed in the adjacent mucosa of the EGCs compared with the corpus during all periods (all P<0.05). The histological degrees of atrophy and metaplasia in the adjacent mucosa were particularly higher in the patients who underwent eradication due to gastric ulcers. Conclusions Severe gastric atrophy remained in the adjacent mucosa of the EGCs after H. pylori eradication, which may be linked to gastric carcinogenesis. PMID:27706195

  3. Pathobiology of Helicobacter pylori-Induced Gastric Cancer.

    PubMed

    Amieva, Manuel; Peek, Richard M

    2016-01-01

    Colonization of the human stomach by Helicobacter pylori and its role in causing gastric cancer is one of the richest examples of a 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 have indicated that subtle mismatches between host and microbe genetic traits greatly affect the risk of gastric cancer. The ability of H pylori and its oncoprotein CagA to reprogram epithelial cells and activate properties of stemness show the sophisticated relationship between 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.

  4. ATOH1 Can Regulate the Tumorigenicity of Gastric Cancer Cells by Inducing the Differentiation of Cancer Stem Cells

    PubMed Central

    Han, Myoung-Eun; Baek, Su-Jin; Kim, Seon-Young; Kang, Chi-Dug; Oh, Sae-Ock

    2015-01-01

    Cancer stem cells (CSCs) have been shown to mediate tumorigenicity, chemo-resistance, radio-resistance and metastasis, which suggest they be considered therapeutic targets. Because their differentiated daughter cells are no longer tumorigenic, to induce the differentiation of CSCs can be one of strategies which can eradicate CSCs. Here we show that ATOH1 can induce the differentiation of gastric cancer stem cells (GCSCs). Real time PCR and western blot analysis showed that ATOH1 was induced during the differentiation of GCSCs. Furthermore, the lentivirus-induced overexpression of ATOH1 in GCSCs and in gastric cancer cell lines significantly induced differentiation, reduced proliferation and sphere formation, and reduced in vivo tumor formation in the subcutaneous injection and liver metastasis xenograft models. These results suggest ATOH1 be considered for the development of a differentiation therapy for gastric cancer. PMID:25950549

  5. Effect of Helicobacter pylori Infection on the Composition of Gastric Microbiota in the Development of Gastric Cancer

    PubMed Central

    Cao, Lei; Yu, Jun

    2015-01-01

    Background Gastric cancer is one of the most common cancer types worldwide. In China, gastric cancer has become one of the major threats for public health, ranking second on incidence and third on cause of cancer death. Despite the common risk factors that promote the development of gastric cancer, the huge quantity of microorganism colonies within the gastrointestinal tract, particularly Helicobacter pylori infection, demonstrates a correlation with chronic inflammation and gastric carcinogenesis, as epidemiological studies have determined that H. pylori infection confers approximately 75% of the attributable risk for gastric cancer. Summary The current article draws an overview on the correlation between the microbiota, inflammation and gastric tumorigenesis. H. pylori infection has been identified as the main risk factor as it triggers epithelial barrier disruption, survival signaling as well as genetic/epigenetic modulation. Apart from H. pylori, the existence of a diverse and complex composition of microbiota in the stomach has been identified, which supports a role of microbiota in the development of gastric cancer. Moreover, metagenomics studies focused on the composition and function of the microbiota have associated microbiota with gastric metabolic diseases and even tumorigenesis. Apart from the gastric microbiota, inflammation is another identified contributor to cancer development as well. Key Message Though H. pylori infection and the non-H. pylori microbiota play a role in gastric cancer, the properties of gastric microbiota and mechanisms by which they participate in the genesis of gastric cancer are still not clearly depicted. Moreover, it remains to be understood how the presence of microbiota along with H. pylori infection affects the progress from gastric disease to cancer. Practical Implications This article summarized a clue of the current studies on microbiota, H. pylori infection and the progression from gastric disease to cancer. PMID

  6. Differential Proteomic Analysis of Noncardia Gastric Cancer from Individuals of Northern Brazil

    PubMed Central

    Leal, Mariana Ferreira; Chung, Janete; Calcagno, Danielle Queiroz; Assumpção, Paulo Pimentel; Demachki, Samia; da Silva, Ismael Dale Cotrim Guerreiro; Chammas, Roger; Burbano, Rommel Rodríguez; de Arruda Cardoso Smith, Marília

    2012-01-01

    Gastric cancer is the second leading cause of cancer-related death worldwide. The identification of new cancer biomarkers is necessary to reduce the mortality rates through the development of new screening assays and early diagnosis, as well as new target therapies. In this study, we performed a proteomic analysis of noncardia gastric neoplasias of individuals from Northern Brazil. The proteins were analyzed by two-dimensional electrophoresis and mass spectrometry. For the identification of differentially expressed proteins, we used statistical tests with bootstrapping resampling to control the type I error in the multiple comparison analyses. We identified 111 proteins involved in gastric carcinogenesis. The computational analysis revealed several proteins involved in the energy production processes and reinforced the Warburg effect in gastric cancer. ENO1 and HSPB1 expression were further evaluated. ENO1 was selected due to its role in aerobic glycolysis that may contribute to the Warburg effect. Although we observed two up-regulated spots of ENO1 in the proteomic analysis, the mean expression of ENO1 was reduced in gastric tumors by western blot. However, mean ENO1 expression seems to increase in more invasive tumors. This lack of correlation between proteomic and western blot analyses may be due to the presence of other ENO1 spots that present a slightly reduced expression, but with a high impact in the mean protein expression. In neoplasias, HSPB1 is induced by cellular stress to protect cells against apoptosis. In the present study, HSPB1 presented an elevated protein and mRNA expression in a subset of gastric cancer samples. However, no association was observed between HSPB1 expression and clinicopathological characteristics. Here, we identified several possible biomarkers of gastric cancer in individuals from Northern Brazil. These biomarkers may be useful for the assessment of prognosis and stratification for therapy if validated in larger clinical study

  7. MicroRNAs as potential biomarkers for gastric cancer

    PubMed Central

    Liu, Han-Shao; Xiao, Hua-Sheng

    2014-01-01

    Gastric cancer is the fourth most common cancer in the world and the second leading cause of cancer-related death. More than 80% of diagnoses occur at the middle to late stage of the disease, highlighting an urgent need for novel biomarkers detectable at earlier stages. Recently, aberrantly expressed microRNAs (miRNAs) have received a great deal of attention as potential sensitive and accurate biomarkers for cancer diagnosis and prognosis. This review summarizes the current knowledge about potential miRNA biomarkers for gastric cancer that have been reported in the publicly available literature between 2008 and 2013. Available evidence indicates that aberrantly expressed miRNAs in gastric cancer correlate with tumorigenesis, tumor proliferation, distant metastasis and invasion. Furthermore, tissue and cancer types can be classified using miRNA expression profiles and next-generation sequencing. As miRNAs in plasma/serum are well protected from RNases, they remain stable under harsh conditions. Thus, potential functions of these circulating miRNAs can be deduced and may implicate their diagnostic value in cancer detection. Circulating miRNAs, as well as tissue miRNAs, may allow for the detection of gastric cancer at an early stage, prediction of prognosis, and monitoring of recurrence and/or lymph node metastasis. Taken together, the data suggest that the participation of miRNAs in biomarker development will enhance the sensitivity and specificity of diagnostic and prognostic tests for gastric cancer. PMID:25232237

  8. Phlegmonous Gastritis with Early Gastric Cancer

    PubMed Central

    Kim, Kyung Hee; Kim, Young-Woo; Moon, Hae; Choi, Jee Eun; Cho, Soo-Jeong; Lee, Jong Yeul; Choi, Il Ju

    2016-01-01

    Phlegmonous gastritis is a rare and rapidly progressive bacterial infection of the stomach wall, with a high mortality rate. Antibiotics with or without surgical treatment are required for treatment. We present a case in which phlegmonous gastritis occurred during the diagnostic evaluation of early gastric cancer. The patient showed improvement after antibiotic treatment, but attempted endoscopic submucosal dissection failed because of submucosal pus. We immediately applied argon plasma coagulation since surgical resection was also considered a high-risk procedure because of the submucosal pus and multiple comorbidities. However, there was local recurrence two years later, and the patient underwent subtotal gastrectomy with lymph node dissection. Considering the risk of incomplete treatment immediately after recovery from phlegmonous gastritis and that recurrent disease can be more difficult to manage, delaying treatment and evaluation until after complete recovery of PG might be a better option in this particular clinical situation. PMID:27752398

  9. Changing strategies for target therapy in gastric cancer

    PubMed Central

    Lee, Suk-young; Oh, Sang Cheul

    2016-01-01

    In spite of a worldwide decrease in the incidence of gastric cancer, this malignancy still remains one of the leading causes of cancer mortality. Great efforts have been made to improve treatment outcomes in patients with metastatic gastric cancer, and the introduction of trastuzumab has greatly improved the overall survival. The trastuzumab treatment took its first step in opening the era of molecular targeted therapy, however several issues still need to be resolved to increase the efficacy of targeted therapy. Firstly, many patients with metastatic gastric cancer who receive trastuzumab in combination with chemotherapeutic agents develop resistance to the targeted therapy. Secondly, many clinical trials testing novel molecular targeted agents with demonstrated efficacy in other malignancies have failed to show benefit in patients with metastatic gastric cancer, suggesting the importance of the selection of appropriate indications according to molecular characteristics in application of targeted agents. Herein, we review the molecular targeted agents currently approved and in use, and clinical trials in patients with metastatic gastric cancer, and demonstrate the limitations and future direction in treatment of advanced gastric cancer. PMID:26811656

  10. [Clinical aspect of new international gastric cancer staging system].

    PubMed

    Liang, Han

    2013-02-01

    The 7th UICC/AJCC Gastric Cancer TNM Staging System includes major revisions of pT and pN classification. The Japanese Classification and UICC/AJCC TNM System have reached consistency in staging of gastric cancer. There are some new topics of lymphadenectomy in the new guidelines. The new TNM system accepts the database from Japan and Korea and it will be more accurate to predict the prognosis of gastric cancer patients. The rationality of splenectomy, total bursectomy, dissection of No.13 and No.14 lymph nodes is still not very clear and needs more evidences. D2 lymphadenectomy is the recommended surgical approach both in Eastern and Western countries. The benefit of paraaortic lymphadenectmoy for selected patients needs further evidences as well. The international gastric cancer staging project will collect the data from 23 countries and the new staging system will be applicable worldwide. PMID:23446465

  11. [Prevention of gastric cancer by Helicobacter pylori eradication].

    PubMed

    Asaka, Masahiro

    2009-08-01

    Though the relationship between Helicobacter pylori (H. pylori) infection and gastric cancer has been proved in epidemiological studies and animal experiments, the prophylactic effect of H. pylori eradication is controversial in human studies. A large-scale clinical study performed by the JAPANGAST Study Group has confirmed that the eradication of H. pylori undoubtedly decreases the incidence of metachronous gastric cancer after endoscopic mucosal resection as published in The Lancet (372: 392-397, 2008). This study shows gastric cancer is a kind of infectious disease, not a lifestyle-related disease, and can thus be averted by preventing or curing the infection, suggesting the eradication of H. pylori might be indicated to prevent development of gastric cancers. PMID:19692758

  12. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in gastric cancer

    PubMed Central

    Seshadri, Ramakrishnan Ayloor; Glehen, Olivier

    2016-01-01

    Gastric cancer associated peritoneal carcinomatosis (GCPC) has a poor prognosis with a median survival of less than one year. Systemic chemotherapy including targeted agents has not been found to significantly increase the survival in GCPC. Since recurrent gastric cancer remains confined to the abdominal cavity in many patients, regional therapies like aggressive cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have been investigated for GCPC. HIPEC has been used for three indications in GC- as an adjuvant therapy after a curative surgery, HIPEC has been shown to improve survival and reduce peritoneal recurrences in many randomised trials in Asian countries; as a definitive treatment in established PC, HIPEC along with CRS is the only therapeutic modality that has resulted in long-term survival in select groups of patients; as a palliative treatment in advanced PC with intractable ascites, HIPEC has been shown to control ascites and reduce the need for frequent paracentesis. While the results of randomised trials of adjuvant HIPEC from western centres are awaited, the role of HIPEC in the treatment of GCPC is still evolving and needs larger studies before it is accepted as a standard of care. PMID:26811651

  13. Lysyl oxidase is a tumor suppressor gene inactivated by methylation and loss of heterozygosity in human gastric cancers.

    PubMed

    Kaneda, Atsushi; Wakazono, Kuniko; Tsukamoto, Tetsuya; Watanabe, Naoko; Yagi, Yukiko; Tatematsu, Masae; Kaminishi, Michio; Sugimura, Takashi; Ushijima, Toshikazu

    2004-09-15

    Lysyl oxidase (LOX) and HRAS-like suppressor (HRASLS) are silenced in human gastric cancers and are reported to have growth-suppressive activities in ras-transformed mouse/rat fibroblasts. Here, we analyzed whether or not LOX and HRASLS are tumor suppressor genes in human gastric cancers. Loss of heterozygosity and promoter methylation of LOX were detected in 33% (9 of 27) and 27% (26 of 96) of gastric cancers, respectively. Biallelic methylation and loss of heterozygosity with promoter methylation were also demonstrated in gastric cancers. Silencing of LOX was also observed in colon, lung, and ovarian cancer cell lines. As for mutations, only one possible somatic mutation was found by analysis of 96 gastric cancer samples and 58 gastric and other cancer cell lines. When LOX was introduced into a gastric cancer cell line, MKN28, in which LOX and HRASLS were silenced, it reduced the number of anchorage-dependent colonies to 57 to 61%, and the number of anchorage-independent colonies to 11 to 23%. Sizes of tumors formed in nude mice were reduced to 19 to 26%. Growth suppression in soft agar assay was also observed in another gastric cancer cell line, KATOIII. On the other hand, neither loss of heterozygosity nor a somatic mutation was detected in HRASLS, and its introduction into MKN28 did not suppress the growth in vitro or in vivo. These data showed that LOX is a tumor suppressor gene inactivated by methylation and loss of heterozygosity in gastric cancers, and possibly also in other cancers. PMID:15374948

  14. Gastric Cancer: Molecular and Clinical Dimensions

    PubMed Central

    Wadhwa, Roopma; Song, Shumei; Lee, Ju-Seog; Yao, Yixin; Wei, Qingyi; Ajani, Jaffer A.

    2014-01-01

    Gastric cancer (GC) imposes a significant health burden around the globe despite its declining incidence. GC is often diagnosed in advanced stages and carries a poor prognosis. In depth understanding of molecular underpinnings of GC has lagged behind many other cancers of its magnitude, as a result our knowledge base for identifying germline susceptibility traits for risk and somatic drivers of progression (to identify novel therapeutic targets) is limited. A few germline (PLCE1) and somatic (ERBB2, ERBB3, PTEN, PI3K/AKT/mTOR, FGF, TP53, CDH1, and c-MET) alterations are emerging and some are being pursued in the clinic. Novel somatic gene targets, Arid1a, FAT4, and MLL/MLL3 are of interest. Clinically, variations in the therapeutic approaches for localized GC are evident by geographic regions. These are driven by preferences for the adjunctive strategies and the extent of surgery coupled with philosophical divides. However, there is a greater uniformity in approaches to metastatic cancer, an incurable condition. Having realized only modest successes, the momentum is building for carrying out more phase 3 comparative trials and some are using biomarker-based patient selection. Overall, rapid progress in biotechnology is improving our molecular understanding and can help with new drug discovery. The future prospects are excellent for defining biomarker-based subsets of patients and application of specific therapeutics. However, many challenges remain to be tackled. Here we review representative molecular and clinical dimensions of GC. PMID:24061039

  15. Korean Gastric Cancer Association Nationwide Survey on Gastric Cancer in 2014

    PubMed Central

    2016-01-01

    Purpose The Korean Gastric Cancer Association (KGCA) has conducted nationwide surveys every 5 years, targeting patients who received surgical treatment for gastric cancer. We report the results of the 2014 nationwide survey and compare them to those of the 1995, 1999, 2004, and 2009 surveys. Materials and Methods From March 2015 to January 2016, a standardized case report form was sent to every member of the KGCA via e-mail. The survey consisted of 29 questions, regarding patient demographics as well as tumor-, and surgery-related factors. The completed data forms were analyzed by the KGCA information committee. Results Data on 15,613 patients were collected from 69 institutions. The mean age was 60.9±12.1 years, and the proportion of patients more than 70 years of age increased from 9.1% in 1995 to 25.3% in 2014. Proximal cancer incidence steadily increased from 11.2% in 1995 to 16.0% in 2014. Early gastric cancer incidence consistently increased and accounted for 61.0% of all cases in 2014. The surgical approach was diversified in 2014, and 7,818 cases (50.1%) were treated with a minimally invasive approach. The most common anastomosis was Billroth I (50.2%) after distal gastrectomy, and the proportion of Roux-en-Y anastomoses performed increased to 8.6%. Conclusions The results of this survey are expected to be important data for future studies and to be useful for generating a national cancer control program. PMID:27752390

  16. [Chemotherapy selection through the process of gastric cancer].

    PubMed

    Liu, Tian-Shu

    2012-02-01

    The role of chemotherapy has become more and more important in the whole process of gastric cancer. S-1 or XELOX regimen is regarded as the standard treatment option in adjuvant chemotherapy. First-line chemotherapy in advanced gastric cancer has been established to improve survival, and the benefit from second-line chemotherapy is being acknowledged. More studies are needed to assess the neoadjuvant chemotherapy.

  17. Lentiviral-mediated RNA interference targeting stathmin1 gene in human gastric cancer cells inhibits proliferation in vitro and tumor growth in vivo

    PubMed Central

    2013-01-01

    Background Gastric cancer is highly aggressive disease. Despite advances in diagnosis and therapy, the prognosis is still poor. Various genetic and molecular alterations are found in gastric cancer that underlies the malignant transformation of gastric mucosa during the multistep process of gastric cancer pathogenesis. The detailed mechanism of the gastric cancer development remains uncertain. In present study we investigated the potential role of stathmin1 gene in gastric cancer tumorigenesis and examined the usefulness of RNA interference (RNAi) targeting stathmin1 as a form of gastric cancer treatment. Methods A lentiviral vector encoding a short hairpin RNA (shRNA) targeted against stathmin1 was constructed and transfected into the packaging cells HEK 293 T and the viral supernatant was collected to transfect MKN-45 cells. The transwell chemotaxis assay and the CCK-8 assay were used to measure migration and proliferation of tumor cells, respectively. Quantitative real-time PCR and western blotting were used to detect the expression levels of stathmin1. Results Lentivirus mediated RNAi effectively reduced stathmin1 expression in gastric cells. Significant decreases in stathmin1 mRNA and protein expression were detected in gastric cells carrying lentiviral stathmin-shRNA vector and also significantly inhibited the proliferation, migration in gastric cancer cells and tumorigenicity in Xenograft Animal Models. Conclusions Our findings suggest that stathmin1 overexpression is common in gastric cancer and may play a role in its pathogenesis. Lentivirus mediated RNAi effectively reduced stathmin1 expression in gastric cells. In summary, shRNA targeting of stathmin1 can effectively inhibits human gastric cancer cell growth in vivo and may be a potential therapeutic strategy for gastric cancer. PMID:24040910

  18. Prognostic value of serum tumor abnormal protein in gastric cancer patients

    PubMed Central

    LAN, FENG; ZHU, MING; QI, QIUFENG; ZHANG, YAPING; LIU, YONGPING

    2016-01-01

    Aberrant glycosylation of protein occurs in nearly all types of cancers and has been confirmed to be associated with tumor progression, metastasis and the survival rate of patients. The present study aimed to explore the prognostic value of tumor abnormal protein (TAP) in gastric cancer patients. TAP was detected in the blood of 42 gastric cancer patients and 56 healthy volunteers by using the TAP testing kit. Univariate and multivariate Cox regression analysis were performed to evaluate the prognostic value of TAP. In total, 64.3% of gastric cancer patients were positive for TAP, and TAP was significantly correlated with poor prognosis [progression-free survival (PFS), 4.2 vs. 12.6 months; P=0.043]. TAP [hazard ratio (HR), 64.487; P<0.01), differentiation (HR, 17.279; P<0.01) and TNM stage (HR, 45.480; P<0.01) were found to be independent predictive factors for PFS. Furthermore, Kaplan-Meier curves indicated that TAP is associated with a reduced PFS in gastric cancer patients. The results of the present study therefore indicated that the TAP test has significant prognostic value for gastric cancer patients. PMID:27330802

  19. Sodium butyrate-induced DAPK-mediated apoptosis in human gastric cancer cells.

    PubMed

    Shin, Hyunsoo; Lee, Yeo Song; Lee, Yong Chan

    2012-04-01

    Epigenetic mechanisms of histone acetylation/deacetylation play an important role in the regulation of gene expression associated with the cell cycle and apoptosis. Recently, sodium butyrate, a histone deacetylase (HDAC) inhibitor, has been shown to exhibit anticancer effects via differentiation and apoptosis of cancer cells. Sodium butyrate may be a potential anticancer chemotherapeutic drug; however, the precise mechanism underlying the anticancer effects of sodium butyrate has not been clearly elucidated. In the present study, we investigated the role of death-associated protein kinase (DAPK) on the apoptosis of human gastric cancer cells induced by sodium butyrate. We observed that sodium butyrate induced apoptosis in human gastric cancer cells. Treatment with the HDAC inhibitor sodium butyrate increased the expression of caspase-3 and DAPK1/2 genes but decreased the expression of Bcl-2 in human gastric cancer cells. The expression of DAPK3, p53 and p21 were not altered by sodium butyrate treatment. Analysis of the general expression patterns revealed that sodium butyrate increased the expression of DAPK1/2 but decreased the expression of FAK and induced changes in the proliferation of apoptosis-related genes in human gastric cancer cells. These data suggest that DAPK expression prompts apoptosis by reducing the FAK protein level in sodium butyrate-induced apoptosis of human gastric cancer cells.

  20. Prevention Strategies for Gastric Cancer: A Global Perspective

    PubMed Central

    Park, Jin Young; von Karsa, Lawrence

    2014-01-01

    Despite the substantial burden of gastric cancer worldwide, population strategies for primary prevention have not been introduced in any country. Recognizing the causal role of Helicobacter pylori infection, there is increasing interest in population-based programs to eradicate the infection to prevent gastric cancer. Nonetheless, the paucity of available evidence on feasibility and effectiveness has prevented implementation of this approach. There are very few secondary prevention programs based on screening with endoscopy or radiography, notably in the Republic of Korea and Japan, two of the countries with the highest incidence rates of gastric cancer. In Korea, where the organized screening program is in place, survival rate of gastric cancer is as high as 67%. More research is needed to quantify the specific contribution of the screening program to observed declines in mortality rates. Gastric cancer screening is unlikely to be feasible in many Low-Middle Income Countries where the gastric cancer burden is high. Prevention strategies are still under development and the optimal approach may differ depending on local conditions and societal values. The present review gives an overview of the etiology and burden of the disease, and possible prevention strategies for countries and regions confronted with a significant burden of disease. PMID:25505712

  1. Perioperative chemotherapy for resectable gastric cancer: MAGIC and beyond.

    PubMed

    Choi, Audrey H; Kim, Joseph; Chao, Joseph

    2015-06-28

    Over the last 15 years, there have been major advances in the multimodal treatment of gastric cancer, in large part due to several phase III studies showing the treatment benefits of neoadjuvant and adjuvant chemotherapy and chemoradiation protocols. The objective of this editorial is to review the current high-level evidence supporting the use of chemotherapy, chemoradiation and anti-HER2 agents in both the neoadjuvant and adjuvant settings, as well as to provide a clinical framework for use of this data based on our own institutional protocol for gastric cancer. Major studies reviewed include the SWOG/INT 0116, Medical Research Council Adjuvant Gastric Infusional Chemotherapy (MAGIC), CLASSIC, ACTS-GC, Adjuvant Chemoradiation Therapy in Stomach Cancer (ARTIST) and Trastuzumab for Gastric Cancer trials. Although these studies have demonstrated that multiple approaches in terms of the timing and therapy for gastric cancer are effective, no standard of care is widely accepted and questions regarding the optimal timing of chemotherapy, the benefit of radiotherapy, the minimum required extent of lymphadenectomy and optimal chemotherapy regimen still exist. Protocols from the upcoming ARTIST II, CRITICS, TOPGEAR, Neo-AEGIS and MAGIC-B studies are outlined, and results from these studies will provide critical information regarding optimal timing and treatment regimen. Additionally, the future directions of gastric cancer research predicated on molecular profiling and tailored therapies based on targetable genetic alterations in individual patient's tumors are addressed.

  2. Benefits and harms of endoscopic screening for gastric cancer.

    PubMed

    Hamashima, Chisato

    2016-07-28

    Gastric cancer has remained a serious burden worldwide, particularly in East Asian countries. However, nationwide prevention and screening programs for gastric cancer have not yet been established in most countries except in South Korea and Japan. Although evidence regarding the effectiveness of endoscopic screening for gastric cancer has been increasingly accumulated, such evidence remains weak because it is based on results from studies other than randomized controlled trials. Specifically, evidence was mostly based on the results of cohort and case-control studies mainly conducted in South Korea and Japan. However, the consistent positive results from these studies suggest promising evidence of mortality reduction from gastric cancer by endoscopic screening. The major harms of endoscopic screening include infection, adverse effects, false-positive results, and overdiagnosis. Despite the possible harms of endoscopic screening, information regarding these harms remains insufficient. To provide appropriate cancer screening, a balance of benefits and harms should always be considered when cancer screening is introduced as a public policy. Quality assurance is very important for the implementation of cancer screening to provide high-quality and safe screening and minimize harms. Endoscopic screening for gastric cancer has shown promising results, and thus deserves further evaluation to reliably establish its effectiveness and optimal use. PMID:27605874

  3. Benefits and harms of endoscopic screening for gastric cancer

    PubMed Central

    Hamashima, Chisato

    2016-01-01

    Gastric cancer has remained a serious burden worldwide, particularly in East Asian countries. However, nationwide prevention and screening programs for gastric cancer have not yet been established in most countries except in South Korea and Japan. Although evidence regarding the effectiveness of endoscopic screening for gastric cancer has been increasingly accumulated, such evidence remains weak because it is based on results from studies other than randomized controlled trials. Specifically, evidence was mostly based on the results of cohort and case-control studies mainly conducted in South Korea and Japan. However, the consistent positive results from these studies suggest promising evidence of mortality reduction from gastric cancer by endoscopic screening. The major harms of endoscopic screening include infection, adverse effects, false-positive results, and overdiagnosis. Despite the possible harms of endoscopic screening, information regarding these harms remains insufficient. To provide appropriate cancer screening, a balance of benefits and harms should always be considered when cancer screening is introduced as a public policy. Quality assurance is very important for the implementation of cancer screening to provide high-quality and safe screening and minimize harms. Endoscopic screening for gastric cancer has shown promising results, and thus deserves further evaluation to reliably establish its effectiveness and optimal use.

  4. Benefits and harms of endoscopic screening for gastric cancer

    PubMed Central

    Hamashima, Chisato

    2016-01-01

    Gastric cancer has remained a serious burden worldwide, particularly in East Asian countries. However, nationwide prevention and screening programs for gastric cancer have not yet been established in most countries except in South Korea and Japan. Although evidence regarding the effectiveness of endoscopic screening for gastric cancer has been increasingly accumulated, such evidence remains weak because it is based on results from studies other than randomized controlled trials. Specifically, evidence was mostly based on the results of cohort and case-control studies mainly conducted in South Korea and Japan. However, the consistent positive results from these studies suggest promising evidence of mortality reduction from gastric cancer by endoscopic screening. The major harms of endoscopic screening include infection, adverse effects, false-positive results, and overdiagnosis. Despite the possible harms of endoscopic screening, information regarding these harms remains insufficient. To provide appropriate cancer screening, a balance of benefits and harms should always be considered when cancer screening is introduced as a public policy. Quality assurance is very important for the implementation of cancer screening to provide high-quality and safe screening and minimize harms. Endoscopic screening for gastric cancer has shown promising results, and thus deserves further evaluation to reliably establish its effectiveness and optimal use. PMID:27605874

  5. Green tea and the risk of gastric cancer: Epidemiological evidence

    PubMed Central

    Hou, I-Chun; Amarnani, Saral; Chong, Mok T; Bishayee, Anupam

    2013-01-01

    Gastric cancer (GC) is one of the leading causes of cancer death in the world. Numerous efforts are being made to find chemoprotective agents able to reduce its risk. Amongst these, green tea has been reported to have a protective effect against stomach cancer. This article aims to critically evaluate all epidemiological studies reporting an association between green tea consumption and GC risk. MEDLINE, EBSCOHOST and Google Scholar were used to search for clinical trials of green tea and its correlation to stomach cancer. Studies include cohort and case-control studies. Outcome of interests are inverse association, no association, and positive association. Seventeen epidemiologic studies were reviewed. Eleven studies were conducted in Japan, five in China, and one with Japanese descendent in Hawaii. Ten case-control studies and seven cohort studies were included. The relative risks or odds ratio of GC for the highest level of green tea consumption was compared. Seven studies suggested no association, eight an inverse association, and one a positive association. One study had shown a significantly lowered GC risk when tea was served warm to cold. Another study also showed a significantly risk with lukewarm tea. All studies that analyzed men and women separately have suggested a reduced risk in women than in men, albeit no significant difference. This review demonstrates that there is insufficient information to support green tea consumption reduces the risk of GC. More studies on the subject matter are warranted. PMID:23840110

  6. Helicobacter pylori eradication for preventing gastric cancer.

    PubMed

    Lu, Bin; Li, Meng

    2014-05-21

    Helicobacter pylori (H. pylori) infection is a major risk factor for gastric cancer (GC) development, which is one of the most challenging malignant diseases worldwide with limited treatments. In the multistep pathogenesis of GC, H. pylori infection slowly induces chronic active gastritis, which progresses through the premalignant stages of atrophic gastritis, intestinal metaplasia, and dysplasia, and then finally to GC. Although eradication of H. pylori is a reasonable approach for the prevention of GC, there have been some contradictory reports, with only some long-term follow-up data showing efficacy of this approach. The inconsistencies are likely due to the insufficient number of participants, relatively short follow-up periods, poor quality of study designs, and the degree and extent of preneoplastic changes at the time of H. pylori eradication. This review analyzes recent high-quality studies to resolve the discrepancies regarding the eradication of H. pylori for GC prevention. The relationship between H. pylori eradication and GC/precancerous lesions/metachronous GC is examined, and the cost-effectiveness of this strategy in the prevention of GC is assessed. Although it is assumed that eradication of H. pylori has the potential to prevent GC, the feasibility and appropriate timing of this strategy for cancer prevention remain to be determined. As a result, additional well-designed trials with longer follow-up periods are needed to clarify this issue.

  7. Effects of constituents of Amomum xanthioides on gastritis in rats and on growth of gastric cancer cells.

    PubMed

    Lee, Yong Soo; Kang, Min Hee; Cho, So Yean; Jeong, Choon Sik

    2007-04-01

    In this study we investigated the effects of constituents of Amomum xanthioides (AX) on gastritis in rats and on the growth of human gastric cancer cells. The ethanol extract of Amomum xanthioides significantly inhibited HCl ethanol-induced gastric lesions and the growth of Helicobacter pylori (H. pylon). The ethanol extract of AX was further fractionated with hexane, chloroform, butanol and H20. Among these fractions, oral treatment with the butanol fraction at a dose of 350 mg/kg was the most effective at preventing HCl* ethanol-induced gastric lesions. In pylorus ligated rats, the butanol fraction also decreased the volume of gastric secretion and gastric acid output. We isolated six subfractions of the butanol fraction using open column chromatography. Subfraction 4 (150 mg/kg) significantly inhibited HCl* ethanol-induced gastric lesions and gastric secretion in pylorus ligated rats. Using GC-MS we identified the constituents of subfraction 4 to be five aliphatic compounds, 1-hexadecene, 1-nonadecene, cycloeicosane, 1-octadecene and cyclotetracosane. In addition, subfraction 4 reduced cell viability in a dose-dependent manner in human gastric cancer cells (AGS, KATOIII and SNU638). It also increased intracellular Ca2+ concentration in SNU638 cells, an effect that was significantly inhibited by dantrolene, a Ca2+ release blocker. Moreover, dantrolene significantly inhibited subfraction 4-induced cytotoxicity. Taken together, these results suggest that subfraction 4 of the butanol extract of AX has an anti-gastritic effect in rats and is cytotoxic to human gastric cancer cells. The mechanism of its anti-gastritic action may be associated with the inhibition of secretion of gastric acid and anti-H. pylori action. Its cytotoxicity against human gastric cancer cells may be, at least in part, mediated by intracellular Ca2+ dyshomeostasis. From these results, we suggest that AX may be useful for the treatment of gastritis and gastric cancer. PMID:17489359

  8. MYC, FBXW7 and TP53 copy number variation and expression in Gastric Cancer

    PubMed Central

    2013-01-01

    Background MYC deregulation is a common event in gastric carcinogenesis, usually as a consequence of gene amplification, chromosomal translocations, or posttranslational mechanisms. FBXW7 is a p53-controlled tumor-suppressor that plays a role in the regulation of cell cycle exit and reentry via MYC degradation. Methods We evaluated MYC, FBXW7, and TP53 copy number, mRNA levels, and protein expression in gastric cancer and paired non-neoplastic specimens from 33 patients and also in gastric adenocarcinoma cell lines. We also determined the invasion potential of the gastric cancer cell lines. Results MYC amplification was observed in 51.5% of gastric tumor samples. Deletion of one copy of FBXW7 and TP53 was observed in 45.5% and 21.2% of gastric tumors, respectively. MYC mRNA expression was significantly higher in tumors than in non-neoplastic samples. FBXW7 and TP53 mRNA expression was markedly lower in tumors than in paired non-neoplastic specimens. Moreover, deregulated MYC and FBXW7 mRNA expression was associated with the presence of lymph node metastasis and tumor stage III-IV. Additionally, MYC immunostaining was more frequently observed in intestinal-type than diffuse-type gastric cancers and was associated with MYC mRNA expression. In vitro studies showed that increased MYC and reduced FBXW7 expression is associated with a more invasive phenotype in gastric cancer cell lines. This result encouraged us to investigate the activity of the gelatinases MMP-2 and MMP-9 in both cell lines. Both gelatinases are synthesized predominantly by stromal cells rather than cancer cells, and it has been proposed that both contribute to cancer progression. We observed a significant increase in MMP-9 activity in ACP02 compared with ACP03 cells. These results confirmed that ACP02 cells have greater invasion capability than ACP03 cells. Conclusion In conclusion, FBXW7 and MYC mRNA may play a role in aggressive biologic behavior of gastric cancer cells and may be a useful

  9. 9th Seah Cheng Siang Memorial Lecture: gastric cancer--where are we now?

    PubMed

    Lam, S K

    1999-11-01

    balance between proliferation and apoptosis may be uncoupled by genetic mutations. It is believed that as a result of the accumulation of molecular genetic abnormalities, a cancer eventually develops and metastasizes. p53 mutation, cyclin overexpression (especially in intestinal type), microsatellite instability, down regulation of E-cadherin (especially in diffuse type), and telomerase reactivation are some prominent examples. These molecular abnormalities have the potential for screening, early detection and prognostication. Fruits and vegetables, green tea, alpha-tocopherol and other micronutrients such as selenium have been shown to reduce the risk for gastric cancer. In fact, it has been reported that diet consisting of vegetables and fruits, low in salt, together with the avoidance of cigarette smoking would prevent two-thirds to three-quarters of gastric cancer. Furthermore, eradication of H. pylori, and for that matter future vaccination, has the theoretical potential of preventing gastric cancer, and the potential use of COX2 inhibiting NSAID in inducing apoptosis may reverse precancerous conditions of the stomach. Both approaches are being intensely studied.

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

    PubMed Central

    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 < 0.0001). When stratified by age, the prevalence was highest among young patients, and tended to decrease in patients aged 50 years or older. The anti-East-Asian CagA-specific antibody was negative in 99.4% of H. pylori-positive Mongolian patients. Chronic inflammation, neutrophil activity, glandular atrophy, and intestinal metaplasia scores were significantly lower in Mongolian compared to Japanese H. pylori-positive patients (P < 0.0001), with the exception of the intestinal

  11. Stromal-Based Signatures for the Classification of Gastric Cancer.

    PubMed

    Uhlik, Mark T; Liu, Jiangang; Falcon, Beverly L; Iyer, Seema; Stewart, Julie; Celikkaya, Hilal; O'Mahony, Marguerita; Sevinsky, Christopher; Lowes, Christina; Douglass, Larry; Jeffries, Cynthia; Bodenmiller, Diane; Chintharlapalli, Sudhakar; Fischl, Anthony; Gerald, Damien; Xue, Qi; Lee, Jee-Yun; Santamaria-Pang, Alberto; Al-Kofahi, Yousef; Sui, Yunxia; Desai, Keyur; Doman, Thompson; Aggarwal, Amit; Carter, Julia H; Pytowski, Bronislaw; Jaminet, Shou-Ching; Ginty, Fiona; Nasir, Aejaz; Nagy, Janice A; Dvorak, Harold F; Benjamin, Laura E

    2016-05-01

    Treatment of metastatic gastric cancer typically involves chemotherapy and monoclonal antibodies targeting HER2 (ERBB2) and VEGFR2 (KDR). However, reliable methods to identify patients who would benefit most from a combination of treatment modalities targeting the tumor stroma, including new immunotherapy approaches, are still lacking. Therefore, we integrated a mouse model of stromal activation and gastric cancer genomic information to identify gene expression signatures that may inform treatment strategies. We generated a mouse model in which VEGF-A is expressed via adenovirus, enabling a stromal response marked by immune infiltration and angiogenesis at the injection site, and identified distinct stromal gene expression signatures. With these data, we designed multiplexed IHC assays that were applied to human primary gastric tumors and classified each tumor to a dominant stromal phenotype representative of the vascular and immune diversity found in gastric cancer. We also refined the stromal gene signatures and explored their relation to the dominant patient phenotypes identified by recent large-scale studies of gastric cancer genomics (The Cancer Genome Atlas and Asian Cancer Research Group), revealing four distinct stromal phenotypes. Collectively, these findings suggest that a genomics-based systems approach focused on the tumor stroma can be used to discover putative predictive biomarkers of treatment response, especially to antiangiogenesis agents and immunotherapy, thus offering an opportunity to improve patient stratification. Cancer Res; 76(9); 2573-86. ©2016 AACR. PMID:27197264

  12. [Palliative Care for Rectal Cancer Complicated with Gastric Cancer].

    PubMed

    Furukawa, Takeshi; Takahashi, Hitoshi; Tanaka, Kei; Muto, Takaaki

    2015-11-01

    Medical advancements have led to an increase in the number of elderly people. However, standard treatments may sometimes be difficult to use in elderly people. Here, we report the case of an elderly patient with rectal and gastric cancer who refused radical surgery. The patient was an 83-year-old man who had type-2 diabetes, hypertension, hyperuricemia, mitral valve regurgitation, and mild dementia. Furthermore, he was blind in both eyes owing to glaucoma. He first visited our hospital in 2005. In 2010, he was diagnosed with anemia, but he refused a thorough examination; however, he did consent to take iron supplements. In July 2011, he consulted our hospital for symptoms of frequent diarrhea, and agreed to an examination. After colonoscopy, he was diagnosed with rectal cancer that was becoming obstructive. There were no metastases to other organs, but he was also diagnosed with gastric cancer. As he and his family refused radical surgery, a stoma was constructed. After the operation, he received palliative care but died in September 2013. PMID:26805335

  13. Gastric Stump Cancer: More Than Just Another Proximal Gastric Cancer and Demanding a More Suitable TNM Staging System

    PubMed Central

    Costa-Pinho, André; Pinto-de-Sousa, J.; Barbosa, José; Costa-Maia, J.

    2013-01-01

    Background. Considerable controversy persists about the biological behavior of gastric stump cancer (GSC). The aim of this study is to clarify if this cancer is just another proximal gastric cancer or if it emerges as a distinctive clinicopathologic entity. Methods. This review of a prospectively collected gastric cancer database identified 73 patients with GSC in a single institution between January 1980 and June 2012 and compared them with 328 patients with proximal gastric cancer (PGC) and 291 patients with esophagogastric junction cancer (EGJC). Results. Patients with GSC were predominantly males. Eighty-three percent of GSC penetrated the subserosal or the serosal layers. The median number of lymph nodes retrieved in GSC patients was significantly lower than in PGC patients or in EGJC patients. Cumulative survival curves were not different between GSC, PGC, or EGJC patients. Unlike that observed in PGC and in EGJC, no significant differences in cumulative survival according to the TNM staging system were observed in GSC cases. Conclusions. The outcome of patients with GSC displayed significant differences when compared to those with other proximal gastric cancers concerning the lack of survival association with the TNM staging system. Therefore a more suitable staging system should be designed for these unique cancers. PMID:24151622

  14. A Platform for Gastric Cancer Screening in Low- and Middle-Income Countries

    PubMed Central

    Caprara, Robert; Obstein, Keith L.; Scozzarro, Gabriel; Natali, Christian Di; Beccani, Marco; Morgan, Douglas R.; Valdastri, Pietro

    2015-01-01

    Gastric cancer is the second leading cause of cancer death worldwide and screening programs have had a significant impact on reducing mortality. The majority of cases occur in low- and middle-income countries (LMIC), where endoscopy resources are traditionally limited. In this paper, we introduce a platform designed to enable inexpensive gastric screening to take place in remote areas of LMIC. The system consists of a swallowable endoscopic capsule connected to an external water distribution system by a multi-channel soft tether. Pressurized water is ejected from the capsule to orient the view of the endoscopic camera. After completion of a cancer screening procedure, the outer shell of the capsule and the soft tether can be disposed, while the endoscopic camera is reclaimed without needing further reprocessing. The capsule, measuring 12 mm in diameter and 28 mm in length, is able to visualize the inside of the gastric cavity by combining waterjet actuation and the adjustment of the tether length. Experimental assessment was accomplished through a set of bench trials, ex vivo analysis, and in vivo feasibility validation. During the ex vivo trials, the platform was able to visualize the main landmarks that are typically observed during a gastric cancer screening procedure in less than 8 minutes. Given the compact footprint, the minimal cost of the disposable parts, and the possibility of running on relatively available and inexpensive resources, the proposed platform can potentially widen gastric cancer screening programs in LMIC. PMID:25561586

  15. Berberine modulates cisplatin sensitivity of human gastric cancer cells by upregulation of miR-203.

    PubMed

    You, He-Yi; Xie, Xue-Meng; Zhang, Wei-Jian; Zhu, Heng-Liang; Jiang, Fei-Zhao

    2016-09-01

    Chemotherapeutic resistance is the main reason of the failure in clinical treatment of gastric cancer. Berberine (BER) is the active compound of traditional Chinese medicine Huang Lian. The aim of this present study is to evaluate the effect of BER on cisplatin resistance in gastric cancer cells and to investigate its possible mechanism. Gastric cancer cell lines SGC-7901 and BGC-823 and their respective cisplatin-resistant variants SGC-7901/DDP and BGC-823/DDP were used in this study. We found that BER treatment significantly reversed cisplatin sensitivity and induced caspase-dependent apoptosis in SGC-7901/DDP and BGC-823/DDP cells; BER treatment induced miR-203 expression, and overexpression of miR-203 mimicked the cisplatin-sensitizing effect of BER. Importantly, we showed that miR-203 was able to target the 3'UTR of Bcl-w. Therefore, we conclude that BER treatment reduces cisplatin resistance of gastric cancer cells by modulating the miR-203/Bcl-w apoptotic axis. BER may be a novel agent to enhance chemotherapeutic responses in cisplatin-resistant gastric cancer patients.

  16. Association of amphiregulin with the cetuximab sensitivity of gastric cancer cell lines.

    PubMed

    Kneissl, Julia; Keller, Simone; Lorber, Thomas; Heindl, Stefan; Keller, Gisela; Drexler, Ingo; Hapfelmeier, Alexander; Höfler, Heinz; Luber, Birgit

    2012-08-01

    The therapeutic activity of the epidermal growth factor receptor (EGFR)-directed monoclonal antibody cetuximab in gastric cancer is currently being investigated in clinical studies. Reliable biomarkers for the identification of patients who are likely to benefit from this treatment are not available. In this study, we assessed the activity of cetuximab in five gastric cancer cell lines (AGS, AZ521, Hs746T, LMSU and MKN1). The viability of two of these cell lines, AZ521 and MKN1, was significantly reduced by cetuximab treatment. High expression and secretion levels of the EGFR-binding ligand, amphiregulin (AREG), were associated with cetuximab responsiveness. MET activation and mutations in Kirsten-Ras gene (KRAS) were associated with cetuximab resistance. By introducing a hierarchy between these markers, we established a model that facilitated the correct classification of all five gastric cancer cell lines as cetuximab responsive or non-responsive. The highest priority was allocated to activating KRAS mutations, followed by MET activation and finally by the levels of secreted AREG. In order to validate these results, we used three additional human gastric cancer cell lines (KATOIII, MKN28 and MKN45). In conclusion, we propose that our model allows the response of gastric cancer cell lines to cetuximab treatment to be predicted. PMID:22614881

  17. Involvement of BID translocation in glycyrrhetinic acid and 11-deoxy glycyrrhetinic acid-induced attenuation of gastric cancer growth.

    PubMed

    Lin, Dejian; Zhong, Wei; Li, Juan; Zhang, Bing; Song, Gang; Hu, Tianhui

    2014-01-01

    Glycyrrhetinic acid (GA), the main chemical constituents of licorice, has shown remarkable anticancer activity. However, the side effects limit its widespread use. 11-DOGA is produced through reduction of GA 11-carbonyl to 11-hydroxyl to reduce its side effects, although its anticancer activities are largely unknown. Here, we report that the functional mechanisms of GA and 11-DOGA in gastric cancers, as well as the comparison between these two drugs' pharmacological potential. Firstly, we found that GA and 11-DOGA significantly inhibits the viabilities of gastric cancer cells in dose- and time-dependent manners. Both GA and 11-DOGA induce gastric cancer cells apoptosis and cell cycle arrest in G2 phase by upregulation of p21 and downregulation of cdc2 and cyclin B1. Further studies show that GA and 11-DOGA-induced apoptosis in gastric cancer cells is associated with BID translocation from nucleus to mitochondria. Moreover, GA and 11-DOGA could effectively inhibit tumor formation of gastric cancer cells in nude mice. Comparing with 11-DOGA, GA presents higher toxicity toward gastric cancer cells both in vivo and in vitro. Thus, the elucidation of the functional mechanisms of GA and 11-DOGA-induced attenuation of gastric cancer growth suggests a possible therapeutic role of GA and its derivatives.

  18. THE CYTOLOGICAL DIAGNOSIS OF GASTRIC CANCER

    PubMed Central

    Armstrong, Charles D.; Johnson, William D.; Wilbur, Richard S.; Lack, Arthur J.

    1961-01-01

    Established centers find that cytological study of gastric washings with saline or chymotrypsin, adequately performed, is a valuable diagnostic tool in the detection of early and curable gastric carcinoma. Our experience with a small series of 150 patients, studied by saline gastric washing, has emphasized the difficulties of collection and the particular importance of obtaining, by repeated washings if necessary, an adequate specimen of gastric epithelial cells for diagnosis, before an opinion is given. It seems likely that the cytological method will be of future value in study of the natural history of gastric malignant disease and in detection of its surface lesions in their earliest form in asymptomatic, known-susceptible persons. Further, it should become a complementary part of the “stomach profile” in gastric diagnostic problems, where roentgenologic and gastroscopic studies may be expected to reveal the older, necrotic, or infiltrative lesions; cytological study, the earlier and more superficial stages of disease. PMID:13862364

  19. Exome sequencing identifies early gastric carcinoma as an early stage of advanced gastric cancer.

    PubMed

    Kang, Guhyun; Hwang, Woo Cheol; Do, In-Gu; Wang, Kai; Kang, So Young; Lee, Jeeyun; Park, Se Hoon; Park, Joon Oh; Kang, Won Ki; Jang, Jiryeon; Choi, Min-Gew; Lee, Jun Ho; Sohn, Tae Sung; Bae, Jae Moon; Kim, Sung; Kim, Min Ji; Kim, Seonwoo; Park, Cheol Keun; Kim, Kyoung-Mee

    2013-01-01

    Gastric carcinoma is one of the major causes of cancer-related mortality worldwide. Early detection and treatment leads to an excellent prognosis in patients with early gastric cancer (EGC), whereas the prognosis of patients with advanced gastric cancer (AGC) remains poor. It is unclear whether EGCs and AGCs are distinct entities or whether EGCs are the beginning stages of AGCs. We performed whole exome sequencing of four samples from patients with EGC and compared the results with those from AGCs. In both EGCs and AGCs, a total of 268 genes were commonly mutated and independent mutations were additionally found in EGCs (516 genes) and AGCs (3104 genes). A higher frequency of C>G transitions was observed in intestinal-type compared to diffuse-type carcinomas (P = 0.010). The DYRK3, GPR116, MCM10, PCDH17, PCDHB1, RDH5 and UNC5C genes are recurrently mutated in EGCs and may be involved in early carcinogenesis.

  20. Endoscopic therapy for early gastric cancer: Standard techniques and recent advances in ESD

    PubMed Central

    Kume, Keiichiro

    2014-01-01

    The technique of endoscopic submucosal dissection (ESD) is now a well-known endoscopic therapy for early gastric cancer. ESD was introduced to resect large specimens of early gastric cancer in a single piece. ESD can provide precision of histologic diagnosis and can also reduce the recurrence rate. However, the drawback of ESD is its technical difficulty, and, consequently, it is associated with a high rate of complications, the need for advanced endoscopic techniques, and a lengthy procedure time. Various advances in the devices and techniques used for ESD have contributed to overcoming these drawbacks. PMID:24914364

  1. The angiotensin II type 1 receptor blocker candesartan suppresses proliferation and fibrosis in gastric cancer.

    PubMed

    Okazaki, Mitsuyoshi; Fushida, Sachio; Harada, Shinichi; Tsukada, Tomoya; Kinoshita, Jun; Oyama, Katsunobu; Tajima, Hidehiro; Ninomiya, Itasu; Fujimura, Takashi; Ohta, Tetsuo

    2014-12-01

    Gastric cancer with peritoneal dissemination has poor clinical prognosis because of the presence of rich stromal fibrosis and acquired drug resistance. Recently, Angiotensin II type I receptor blockers such as candesartan have attracted attention for their potential anti-fibrotic activity. We examined whether candesartan could attenuate tumor proliferation and fibrosis through the interaction between gastric cancer cell line (MKN45) cells and human peritoneal mesothelial cells. Candesartan significantly reduced TGF-β1 expression and epithelial-to-mesenchymal transition-like change, while tumor proliferation and stromal fibrosis were impaired. Targeting the Angiotensin II signaling pathway may therefore be an efficient strategy for treatment of tumor proliferation and fibrosis. PMID:25224569

  2. Ischemic Gastropathic Ulcer Mimics Gastric Cancer

    PubMed Central

    Daher, Saleh; Lahav, Ziv; Rmeileh, Ayman Abu; Mizrahi, Meir

    2016-01-01

    Gastric ulcer due to mesenteric ischemia is a rare clinical finding. As a result, few reports of ischemic gastric ulcers have been reported in the literature. The diagnosis of ischemic gastropathy is seldom considered in patients presenting with abdominal pain and gastric ulcers. In this case report, we describe a patient with increasing abdominal pain, weight loss, and gastric ulcers, who underwent extensive medical evaluation and whose symptoms were resistant to medical interventions. Finally he was diagnosed with chronic mesenteric ischemia, and his clinical and endoscopic abnormalities resolved after surgical revascularization of both the superior mesenteric artery and the celiac trunk. PMID:27579191

  3. Advanced gastric cancer: Current treatment landscape and future perspectives

    PubMed Central

    Digklia, Antonia; Wagner, Anna Dorothea

    2016-01-01

    Gastric cancer currently ranks fourth in cancer-related mortality worldwide. In the western world, it is most often diagnosed at an advanced stage, after becoming metastatic at distant sites. Patients with advanced disease (locally advanced or metastatic) have a somber prognosis, with a median overall survival of 10-12 mo, and palliative chemotherapy is the mainstay of treatment. In recent years, novel approaches using inhibition of human epidermal growth factor receptor 2 (HER2) have demonstrated significant improvements in progression-free and overall survival, compared with chemotherapy alone, in first-line treatment of patients with overexpression of HER2. In addition, both second-line chemotherapy and treatment with the vascular endothelial growth factor receptor-inhibitor ramucirumab demonstrated significant benefits in terms of overall survival, compared with best supportive care, in randomized studies. Moreover, ramucirumab in combination with chemotherapy demonstrated further significant benefits in terms of progression-free and overall survival, compared with chemotherapy alone, in second-line treatment for patients with metastatic gastric cancer. A recently published molecular classification of gastric cancer is expected to improve patient stratification and selection for clinical trials and provide a roadmap for future drug development. Nevertheless, despite these developments the prognosis of patients with advanced gastric cancer remains poor. In this review we discuss current standards of care and outline major topics of drug development in gastric cancer. PMID:26937129

  4. Current and emerging therapies in unresectable and recurrent gastric cancer

    PubMed Central

    Jou, Erin; Rajdev, Lakshmi

    2016-01-01

    Gastric cancer is one of the most lethal cancers worldwide despite many advances and options in therapy. As it is often diagnosed at an advanced stage, prognosis is poor with a median overall survival of less than twelve months. Chemotherapy remains the mainstay of treatment for these patients but it confers only a moderate survival advantage. There remains a need for new targeted treatment options and a way to better define patient populations who will benefit from these agents. In the past few years, there has been a better understanding of the biology, molecular profiling, and heterogeneity of gastric cancer. Our increased knowledge has led to the identification of gastric cancer subtypes and to the development of new targeted therapeutic agents. There are now two new targeted agents, trastuzumab and ramucirumab, that have recently been approved for the treatment of advanced and metastatic gastric cancer. There are also many other actively investigated targets, including epidermal growth factor receptor, the phosphatadylinositol 3-kinase/protein kinase B/mammalian target of rapamycin pathway, c-Met, poly ADP-ribose polymerase, and immune checkpoint inhibition. In this review, we discuss the current management of advanced gastric cancer as well as emerging targeted therapies and immunotherapy. PMID:27239108

  5. Anticancer activity of CopA3 dimer peptide in human gastric cancer cells

    PubMed Central

    Lee, Joon Ha; Kim, In-Woo; Kim, Sang-Hee; Yun, Eun-Young; Nam, Sung-Hee; Ahn, Mi-Young; Kang, Dong-Chul; Hwang, Jae Sam

    2015-01-01

    CopA3 is a homodimeric α-helical peptide derived from coprisin which is a defensin-like antimicrobial peptide that was identified from the dung beetle, Copris tripartitus. CopA3 has been reported to have anticancer activity against leukemia cancer cells. In the present study, we investigated the anticancer activity of CopA3 in human gastric cancer cells. CopA3 reduced cell viability and it was cytotoxic to gastric cancer cells in the MTS and LDH release assay, respectively. CopA3 was shown to induce necrotic cell death of the gastric cancer cells by flow cytometric analysis and acridine orange/ethidium bromide staining. CopA3-induced cell death was mediated by specific interactions with phosphatidylserine, a membrane component of cancer cells. Taken together, these data indicated that CopA3 mainly caused necrosis of gastric cancer cells, probably through interactions with phosphatidylserine, which suggests the potential utility of CopA3 as a cancer therapeutic. [BMB Reports 2015; 48(6): 324-329] PMID:25047444

  6. Endoscopic submucosal dissection combined with endoscopic injection sclerotherapy for early gastric cancer on gastric fundal varices.

    PubMed

    Uno, Kaname; Iijima, Katsunori; Koike, Tomoyuki; Abe, Yasuhiko; Asano, Naoki; Yokosawa, Satoshi; Imatani, Akira; Shimosegawa, Tooru

    2012-08-01

    Currently, there is little report of treatment strategy for early gastric cancer (EGC) on gastric fundal varices (GFVs), because controlling GFVs was more challenging than controlling gastric cardiac varices associated with esophageal varices. We first report effective endoscopic treatment of EGC on GFVs of a 77-year-old man with Child-B cirrhosis. Endoscopic ultrasound and multidetector-row computed tomography studies revealed intramucosal EGC on variceal components, supplied from posterior gastric vein and drained to subphrenic vein without gastrorenal shunt. With informed consent, we performed endoscopic submucosal dissection (ESD) after eradication of GFVs by endoscopic injection sclerotherapy (EIS). Histologic assessment revealed curability of ESD and inflammation and fibrosis around EIS site. Thereafter, no recurrence and complication had occurred. To avoid life-threatening bleeding from GFVs, we achieved complete resection by ESD under direct visualization of submucosa after eradication of GFVs by EIS based on the examination of hemodynamics and local relationship between EGC and GFVs.

  7. Gastric Cancer: Descriptive Epidemiology, Risk Factors, Screening, and Prevention

    PubMed Central

    Karimi, Parisa; Islami, Farhad; Anandasabapathy, Sharmila; Freedman, Neal D.; Kamangar, Farin

    2014-01-01

    Less than a century ago, gastric cancer (GC) was the most common cancer in the United States and perhaps throughout the world. Despite its worldwide decline in incidence over the past century, GC remains a major killer across the globe. This article reviews the epidemiology, screening, and prevention of gastric cancer. We first discuss the descriptive epidemiology of GC, including its incidence, survival, and mortality, including trends over time. Next, we characterize the risk factors for gastric cancer, both environmental and genetic. Serological markers and histological precursor lesions of GC and early detection of GC of using these markers is reviewed. Finally, we discuss prevention strategies and provide suggestions for further research. PMID:24618998

  8. Clinical utility of ramucirumab in advanced gastric cancer.

    PubMed

    Chan, Matthew Mk; Sjoquist, Katrin M; Zalcberg, John R

    2015-01-01

    Gastric cancer is currently the third most common cause of cancer deaths worldwide. Prognosis remains poor with most patients presenting with advanced or metastatic disease. A better understanding of angiogenesis has led to the investigation of drugs that inhibit the vascular endothelial growth factor (VEGF) pathway including anti-VEGF antibody therapy (eg, bevacizumab), inhibitors of angiogenic receptor tyrosine kinases (eg, sunitinib, sorafenib, apatinib, regorafenib), and inhibitors of vascular endothelial growth factor receptors (VEGFRs) (eg, ramucirumab). Ramucirumab, a VEGFR-2 inhibitor, is the first anti-angiogenic agent approved by the US Food and Drug Administration for use in the treatment of advanced gastric cancers. This review will focus on the clinical utility and potential use of ramucirumab in advanced gastric cancer.

  9. Phase I and II clinical trials for gastric cancer.

    PubMed

    Khushalani, Nikhil I

    2012-01-01

    Gastric cancer remains a global public health problem with considerable heterogeneity in pathogenesis and clinical presentation across geographic regions. Improved understanding of the molecular biology of this disease has opened avenues for targeted intervention. An individualized treatment approach is required for optimal management of this cancer. Overcoming resistance to therapy requires combining targeted agents with the traditional options of chemotherapy/radiation therapy, and also targeting more than 1 pathway of carcinogenesis at a time. Encouraging molecular hypothesis and biomarker-driven trials will lead to improved patient outcomes and may eventually enable the therapeutic nihilism associated with gastric cancer to be overcome. PMID:22098835

  10. Seom guidelines for the treatment of gastric cancer 2015.

    PubMed

    Martin-Richard, M; Custodio, A; García-Girón, C; Grávalos, C; Gomez, C; Jimenez-Fonseca, P; Manzano, J L; Pericay, C; Rivera, F; Carrato, A

    2015-12-01

    Gastric cancer is the fourth cause of death by cancer in Spain and a significant medical problem. Molecular biology results evidence that gastroesophageal junction tumors and gastric cancer should be considered as two independent entities with a different prognosis and treatment approach. Endoscopic resection in very early tumors is feasible. Neoadjuvant and adjuvant therapy in locally advanced resectable tumor increase overall survival and should be considered standard treatments. In stage IV tumors, platinum-fluoropyrimidine-based schedule, with trastuzumab in HER2-overexpressed tumors, is the first-line treatment. Different therapies in second line have demonstrated in randomized studies their clear benefit in survival improvement.

  11. Chemotherapy in Elderly Patients with Gastric Cancer

    PubMed Central

    Kim, Hyeong Su; Kim, Jung Han; Kim, Ji Won; Kim, Byung Chun

    2016-01-01

    Gastric cancer (GC) is one of the most frequent malignant diseases in the elderly. Systemic chemotherapy showed an improvement of quality of life and survival benefit compared to supportive care alone in patients with advanced GC. Because comorbidities or age-related changes in pharmacokinetics and pharmacodynamics may lead to higher toxicity, however, many oncologists hesitate to recommend elderly patients to receive chemotherapy. Available data suggest that elderly patients with GC are able to tolerate and benefit from systemic chemotherapy to the same extent as younger patients. The age alone should not be the only criteria to preclude effective chemotherapy. However, proper patient selection is extremely important to deliver effective treatment safely. A comprehensive geriatric assessment (CGA) is a useful method to assess life expectancy and risk of morbidity in older patients and to guide providing optimal treatment. Treatment should be personalized based on the nature of the disease, the life expectancy, the risk of complication, and the patient's preference. Combination chemotherapy can be considered for older patients with metastatic GC who are classified as non-frail patients by CGA. For frail or vulnerable patients, however, monotherapy or only symptomatic treatment may be desirable. Targeted agents seem to be promising treatment options for elderly patients with GC considering their better efficacy and less toxicity. PMID:26722364

  12. Clinical significance of MET in gastric cancer

    PubMed Central

    Inokuchi, Mikito; Otsuki, Sho; Fujimori, Yoshitaka; Sato, Yuya; Nakagawa, Masatoshi; Kojima, Kazuyuki

    2015-01-01

    Chemotherapy has become the global standard treatment for patients with metastatic or unresectable gastric cancer (GC), although outcomes remain unfavorable. Many molecular-targeted therapies inhibiting signaling pathways of various tyrosine kinase receptors have been developed, and monoclonal antibodies targeting human epidermal growth factor receptor 2 or vascular endothelial growth factor receptor 2 have become standard therapy for GC. Hepatocyte growth factor and its receptor, c-MET (MET), play key roles in tumor growth through activated signaling pathways from receptor in GC cells. Genomic amplification of MET leads to the aberrant activation found in GC tumors and is related to survival in patients with GC. This review discusses the clinical significance of MET in GC and examines MET as a potential therapeutic target in patients with GC. Preclinical studies in animal models have shown that MET antibodies or small-molecule MET inhibitors suppress tumor-cell proliferation and tumor progression in MET-amplified GC cells. These drugs are now being evaluated in clinical trials as treatments for metastatic or unresectable GC. PMID:26600931

  13. Molecular targeted therapy for advanced gastric cancer

    PubMed Central

    2013-01-01

    Although medical treatment has been shown to improve quality of life and prolong survival, no significant progress has been made in the treatment of advanced gastric cancer (AGC) within the last two decades. Thus, the optimum standard first-line chemotherapy regimen for AGC remains debatable, and most responses to chemotherapy are partial and of short duration; the median survival is approximately 7 to 11 months, and survival at 2 years is exceptionally > 10%. Recently, remarkable progress in tumor biology has led to the development of new agents that target critical aspects of oncogenic pathways. For AGC, many molecular targeting agents have been evaluated in international randomized studies, and trastuzumab, an anti-HER-2 monoclonal antibody, has shown antitumor activity against HER-2-positive AGC. However, this benefit is limited to only ~20% of patients with AGC (patients with HER-2-positive AGC). Therefore, there remains a critical need for both the development of more effective agents and the identification of molecular predictive and prognostic markers to select those patients who will benefit most from specific chemotherapeutic regimens and targeted therapies. PMID:23525404

  14. DNA Methylation as Surrogate Marker For Gastric Cancer

    PubMed Central

    Oh, Jung-Hwan; Jung, Sung-Hoon; Hong, Seung-Jin; Rhyu, Mun-Gan

    2015-01-01

    Stomach cancer remains, stubbornly, highly prevalent in East Asia. Still, stomach cancer has few biomarkers by which it can be predicted. Helicobacter pylori infection, a known carcinogen of stomach cancer, usually goes undetected prior to cancer diagnosis, due to the poor mucosal environments that its related gastric atrophy causes. We propose, herein, an endoscopic-biopsy-based cancer-predicting DNA methylation marker. We semi-quantitatively examined the methylation-variable sites near the CpG-island margins by radioisotope-labeling methylation-specific polymerase chain reaction in association with H. pylori, which increases age-related over-methylation in CpG islands of gastric mucosa. These age-related methylation patterns of the transitional-CpG sites are proposed as useful surrogate markers for stomach cancer. It would be helpful for setting the optimal screening interval for high-risk subjects as well as for estimating the prognosis and the predictability for recurrence of early gastric cancer in patients having undergone endoscopic submucosal dissection. New screening-interval guidelines for gastric cancer should be suggested considering individual risk based on age, severity of atrophy, H. pylori status, and DNA methylation pattern. PMID:26473155

  15. Fifteen-year effects of Helicobacter pylori, garlic, and vitamin treatments on gastric cancer incidence and mortality.

    PubMed

    Ma, Jun-Ling; Zhang, Lian; Brown, Linda M; Li, Ji-You; Shen, Lin; Pan, Kai-Feng; Liu, Wei-Dong; Hu, Yuanreng; Han, Zhong-Xiang; Crystal-Mansour, Susan; Pee, David; Blot, William J; Fraumeni, Joseph F; You, Wei-Cheng; Gail, Mitchell H

    2012-03-21

    In the Shandong Intervention Trial, 2 weeks of antibiotic treatment for Helicobacter pylori reduced the prevalence of precancerous gastric lesions, whereas 7.3 years of oral supplementation with garlic extract and oil (garlic treatment) or vitamin C, vitamin E, and selenium (vitamin treatment) did not. Here we report 14.7-year follow-up for gastric cancer incidence and cause-specific mortality among 3365 randomly assigned subjects in this masked factorial placebo-controlled trial. Conditional logistic regression was used to estimate the odds of gastric cancer incidence, and the Cox proportional hazards model was used to estimate the relative hazard of cause-specific mortality. All statistical tests were two-sided. Gastric cancer was diagnosed in 3.0% of subjects who received H pylori treatment and in 4.6% of those who received placebo (odds ratio = 0.61, 95% confidence interval = 0.38 to 0.96, P = .032). Gastric cancer deaths occurred among 1.5% of subjects assigned H pylori treatment and among 2.1% of those assigned placebo (hazard ratio [HR] of death = 0.67, 95% CI = 0.36 to 1.28). Garlic and vitamin treatments were associated with non-statistically significant reductions in gastric cancer incidence and mortality. Vitamin treatment was associated with statistically significantly fewer deaths from gastric or esophageal cancer, a secondary endpoint (HR = 0.51, 95% CI = 0.30 to 0.87; P = .014). PMID:22271764

  16. RUNX3 is a novel negative regulator of oncogenic TEAD-YAP complex in gastric cancer.

    PubMed

    Qiao, Y; Lin, S J; Chen, Y; Voon, D C-C; Zhu, F; Chuang, L S H; Wang, T; Tan, P; Lee, S C; Yeoh, K G; Sudol, M; Ito, Y

    2016-05-19

    Runt-related transcription factor 3 (RUNX3) is a well-documented tumour suppressor that is frequently inactivated in gastric cancer. Here, we define a novel mechanism by which RUNX3 exerts its tumour suppressor activity involving the TEAD-YAP complex, a potent positive regulator of proliferative genes. We report that the TEAD-YAP complex is not only frequently hyperactivated in liver and breast cancer, but also confers a strong oncogenic activity in gastric epithelial cells. The increased expression of TEAD-YAP in tumour tissues significantly correlates with poorer overall survival of gastric cancer patients. Strikingly, RUNX3 physically interacts with the N-terminal region of TEAD through its Runt domain. This interaction markedly reduces the DNA-binding ability of TEAD that attenuates the downstream signalling of TEAD-YAP complex. Mutation of RUNX3 at Arginine 122 to Cysteine, which was previously identified in gastric cancer, impairs the interaction between RUNX3 and TEAD. Our data reveal that RUNX3 acts as a tumour suppressor by negatively regulating the TEAD-YAP oncogenic complex in gastric carcinogenesis. PMID:26364597

  17. Gastric microbiota and predicted gene functions are altered after subtotal gastrectomy in patients with gastric cancer

    PubMed Central

    Tseng, Ching-Hung; Lin, Jaw-Town; Ho, Hsiu J.; Lai, Zi-Lun; Wang, Chang-Bi; Tang, Sen-Lin; Wu, Chun-Ying

    2016-01-01

    Subtotal gastrectomy (i.e., partial removal of the stomach), a surgical treatment for early-stage distal gastric cancer, is usually accompanied by highly selective vagotomy and Billroth II reconstruction, leading to dramatic changes in the gastric environment. Based on accumulating evidence of a strong link between human gut microbiota and host health, a 2-year follow-up study was conducted to characterize the effects of subtotal gastrectomy. Gastric microbiota and predicted gene functions inferred from 16S rRNA gene sequencing were analyzed before and after surgery. The results demonstrated that gastric microbiota is significantly more diverse after surgery. Ralstonia and Helicobacter were the top two genera of discriminant abundance in the cancerous stomach before surgery, while Streptococcus and Prevotella were the two most abundant genera after tumor excision. Furthermore, N-nitrosation genes were prevalent before surgery, whereas bile salt hydrolase, NO and N2O reductase were prevalent afterward. To our knowledge, this is the first report to document changes in gastric microbiota before and after surgical treatment of stomach cancer. PMID:26860194

  18. Robotic surgery for gastric cancer: a technical review.

    PubMed

    Hyung, Woo Jin; Woo, Yanghee; Noh, Sung Hoon

    2011-12-01

    Minimally invasive gastric cancer surgery is gaining acceptance, especially in the treatment of patients with early gastric cancer. While offering patients the benefits of minimally invasive surgery, laparoscopic surgery is limited by several disadvantages such as altered operating view and lack of versatility in surgical instrumentation. Robotic surgery offers the surgeon the benefit of superior 3D visualization, the freedom of the EndoWrist function, and the tremble-filtered control of the four robotic arms. Due to the technical advantages of the robotic surgical system, robotic surgery may facilitate the expansion of minimally invasive surgery over laparoscopy. The application of robotic surgery for gastric cancer is increasing in experienced centers. Most reports of the robotic operating methods are only slightly modified from the laparoscopic technique. Robotic gastric cancer surgery including radical subtotal gastrectomy with D2 lymph node dissection is technically feasible and safe and results in similar short-term postoperative outcomes when compared to laparoscopic surgery. The role of robotic surgery in gastric cancer is promising but awaits further comparative studies of long-term results and cost-effectiveness. PMID:27628113

  19. Diffuse Type Gastric and Lobular Breast Carcinoma in a Familial Gastric Cancer Patient with an E-Cadherin Germline Mutation

    PubMed Central

    Keller, Gisela; Vogelsang, Holger; Becker, Ingrid; Hutter, Jörg; Ott, Katja; Candidus, Sonja; Grundei, Tobias; Becker, Karl-Friedrich; Mueller, James; Siewert, Jörg R.; Höfler, Heinz

    1999-01-01

    E-Cadherin alterations have been reported frequently in sporadic diffuse type gastric and lobular breast carcinomas. Germline mutations of this gene have been identified recently in several gastric cancer families. We analyzed seven patients with a family history of the disease who had diffuse type gastric cancer diagnosed before the age of 45 for germline mutations in CDH1, the gene encoding the E-cadherin protein. We identified a frameshift mutation in exon 3 in one patient with a strong family history of gastric cancer. The same germline mutation was found in the patient’s mother, who had metachronous development of lobular breast and diffuse type gastric carcinomas. Immunohistochemistry for E-cadherin protein expression revealed an abnormal staining pattern in both of these tumors, suggesting complete inactivation of the cell adhesion molecule. Thus, our finding suggests that besides diffuse type gastric cancer, lobular breast carcinomas may be associated with germline CDH1 mutations. PMID:10433926

  20. Induced nitric oxide synthetase and peroxiredoxin expression in intramucosal poorly differentiated gastric cancer of young patients.

    PubMed

    Hirahashi, Minako; Koga, Yutaka; Kumagai, Reiko; Aishima, Shinichi; Taguchi, Kenichi; Oda, Yoshinao

    2014-04-01

    To investigate the relationship between oxidative stress and gastric carcinogenesis of poorly differentiated adenocarcinoma in young patients, we analyzed the surgically resected specimens of 22 young patients (21-30 years) and 29 older patients (41-72 years) with intramucosal gastric cancer of the poorly differentiated type. We used immunohistochemical staining to evaluate the expression of 8-hydroxydeoxyguanosine (8OHdG), induced nitric oxide synthetase (iNOS), and antioxidant enzymes (thioredoxin [TRX] and peroxiredoxin [PRDX1, 2 and 3]). We assessed these proteins in the cancer, noncancerous gastric foveolar epithelium and noncancerous mucosal neck. In both the young and older patient groups, the 8OHdG and TRX expressions were gradually increased in cancer cells compared with the noncancerous foveolar epithelial cells and the noncancerous mucosal neck cells (P < 0.001). Although the iNOS and PRDXs expressions were increased in the noncancerous mucosal neck cells compared with the noncancerous foveolar epithelial cells, regardless of age (P < 0.001), the iNOS and PRDX2 expression in the cancer cells were significantly reduced in the young patients compared with the older patients (P < 0.001, P < 0.05). In conclusion, the reduced expression of iNOS or PRDX2 may play an important role in the carcinogenesis of gastric cancer associated with Helicobacter pylori-induced chronic active gastritis in young patients.

  1. Regression of Gastric Cancer by Systemic Injection of RNA Nanoparticles Carrying both Ligand and siRNA

    PubMed Central

    Cui, Daxiang; Zhang, Chunlei; Liu, Bing; Shu, Yi; Du, Tong; Shu, Dan; Wang, Kan; Dai, Fangping; Liu, Yanlei; Li, Chao; Pan, Fei; Yang, Yuming; Ni, Jian; Li, Hui; Brand-Saberi, Beate; Guo, Peixuan

    2015-01-01

    Gastric cancer is the second leading cause of cancer-related death worldwide. RNA nanotechnology has recently emerged as an important field due to recent finding of its high thermodynamic stability, favorable and distinctive in vivo attributes. Here we reported the use of the thermostable three-way junction (3WJ) of bacteriophage phi29 motor pRNA to escort folic acid, a fluorescent image marker and BRCAA1 siRNA for targeting, imaging, delivery, gene silencing and regression of gastric cancer in animal models. In vitro assay revealed that the RNA nanoparticles specifically bind to gastric cancer cells, and knock-down the BRCAA1 gene. Apoptosis of gastric cancer cells was observed. Animal trials confirmed that these RNA nanoparticles could be used to image gastric cancer in vivo, while showing little accumulation in crucial organs and tissues. The volume of gastric tumors noticeably decreased during the course of treatment. No damage to important organs by RNA nanoparticles was detectible. All the results indicated that this novel RNA nanotechnology can overcome conventional cancer therapeutic limitations and opens new opportunities for specific delivery of therapeutics to stomach cancer without damaging normal cells and tissues, reduce the toxicity and side effect, improve the therapeutic effect, and exhibit great potential in clinical tumor therapy. PMID:26137913

  2. Regression of Gastric Cancer by Systemic Injection of RNA Nanoparticles Carrying both Ligand and siRNA.

    PubMed

    Cui, Daxiang; Zhang, Chunlei; Liu, Bing; Shu, Yi; Du, Tong; Shu, Dan; Wang, Kan; Dai, Fangping; Liu, Yanlei; Li, Chao; Pan, Fei; Yang, Yuming; Ni, Jian; Li, Hui; Brand-Saberi, Beate; Guo, Peixuan

    2015-07-03

    Gastric cancer is the second leading cause of cancer-related death worldwide. RNA nanotechnology has recently emerged as an important field due to recent finding of its high thermodynamic stability, favorable and distinctive in vivo attributes. Here we reported the use of the thermostable three-way junction (3WJ) of bacteriophage phi29 motor pRNA to escort folic acid, a fluorescent image marker and BRCAA1 siRNA for targeting, imaging, delivery, gene silencing and regression of gastric cancer in animal models. In vitro assay revealed that the RNA nanoparticles specifically bind to gastric cancer cells, and knock-down the BRCAA1 gene. Apoptosis of gastric cancer cells was observed. Animal trials confirmed that these RNA nanoparticles could be used to image gastric cancer in vivo, while showing little accumulation in crucial organs and tissues. The volume of gastric tumors noticeably decreased during the course of treatment. No damage to important organs by RNA nanoparticles was detectible. All the results indicated that this novel RNA nanotechnology can overcome conventional cancer therapeutic limitations and opens new opportunities for specific delivery of therapeutics to stomach cancer without damaging normal cells and tissues, reduce the toxicity and side effect, improve the therapeutic effect, and exhibit great potential in clinical tumor therapy.

  3. WAVE3 promotes epithelial-mesenchymal transition of gastric cancer through upregulation of Snail.

    PubMed

    Yue, Z; Feng, W; Xiangke, L; Liuxing, W; Qingxia, F; Jianbo, G

    2014-12-01

    WAVE3, an actin cytoskeleton remodeling protein overexpressed in many kinds of cancers, has been associated with a lot of metastatic diseases. However, the role and mechanisms of the high expression of WAVE3 in human gastric cancer has not been fully elucidated. Here we demonstrated that WAVE3 was expressed in all six kinds of gastric-cancer cell lines: BGC-823, SGC-7901, AGS, MGC803, MKN28 and MKN45. Furthermore, a correlation was found between aggressiveness of these cell lines and expression of WAVE3. Next, we investigated the role of WAVE3 in SGC-7901 cells and found that upregulating WAVE3 could promote the migration, invasion and proliferation of SGC-7901 cells in vitro. It has been reported that WAVE3 could induce cancer invasion and metastasis by participating epithelial-mesenchymal transition (EMT). However, the mechanisms are not entirely clear. In this study we showed that elevated WAVE3 levels could induce EMT in SGC-7901 cells by dampening the expression of E-cadherin while increasing the expression of vimentin. Elevated WAVE3 levels could also improve the expression of transcription factor Snail. In addition, downregulating Snail could particularly reduce EMT and the metastasis, invasion and proliferation activity in SGC-7901 cells elevated by overexpression of WAVE3. Taken together, we demonstrated that WAVE3 promoted gastric-cancer-cells migration and invasion by taking part in EMT via upregulation of Snail. WAVE3 could be a useful target for gastric-cancer prevention and therapy. PMID:25378074

  4. Factors Associated with Fatigue in Korean Gastric Cancer Survivors

    PubMed Central

    Park, Wan; Lee, Jung-Kwon; Kim, Cho-Rong

    2015-01-01

    Background Gastric cancer is the second most common cancer in Korea. Fatigue is a common symptom among cancer survivors. The aim of this study was to identify factors associated with fatigue in gastric cancer survivors. Methods Data were analyzed from 199 gastric cancer survivors who visited a cancer survivor outpatient clinic from July 2013 to June 2014. Patients were surveyed using a questionnaire containing a fatigue severity scale (FSS) and questions regarding associated symptoms. Participants were divided into fatigue (FSS) and non-fatigue groups based on FSS scores (≥4 and <4, respectively). Age, sex, weight, body mass index, cancer stage, pathology, surgery type, chemotherapy, radiotherapy, comorbid disease, family history of cancer, smoking, alcohol consumption, exercise, and laboratory results were investigated. Results The fatigue and non-fatigue groups contained 42 and 157 survivors, respectively. Their mean age was 58 years, and the mean post-operative period was 6.58 years. Arthralgia (odds ratio [OR], 12.95; 95% confidence interval [CI], 3.21-52.34), dyspnea (OR, 10.54; 95% CI, 2.94-37.80), dyspepsia (OR, 8.26; 95% CI, 2.63-25.96), changed bowel habits (OR, 4.56; 95% CI, 1.09-19.11), anemia (OR, 3.18; 95% CI, 1.26-8.05), and regular exercise (OR, 0.31; 95% CI, 0.12-0.77) were significantly associated with fatigue in gastric cancer survivors, while weight, treatment, and depressive mood were not. Conclusion Arthralgia, dyspnea, dyspepsia, bowel habit change, anemia, and regular exercise are associated with fatigue in gastric cancer survivors. PMID:26634101

  5. Bursectomy for gastric cancer: What does the evidence indicate?

    PubMed

    Barreto, S G; Perwaiz, A; Singh, A; Singh, T; Chaudhary, A

    2015-01-01

    Radical resection of the bursa omentalis (radical bursectomy) as part of a curative resection for gastric cancer has been advised for close to a century. However, the postulated associated morbidity and lack of a clear benefit in terms of survival preclude its routine use. To objectively review the available evidence on the role of bursectomy as part of a curative resection for gastric cancer. A systematic search of the scientific literature was carried out using Embase, PubMed, MedLine and the Cochrane central register of controlled trials for the years 1965-2013 to obtain access to all publications, especially randomized controlled trials (RCTs), systematic reviews and meta-analyses involving bursectomy in gastric cancer with the appropriate specific search terms, namely, "bursectomy," "stomach cancer," "gastric cancer," "survival," "morbidity," "outcomes" and "RCTs". Using the above search strategy, a total of 29 publications was retrieved of which five publications were identified describing bursectomy and its outcomes in gastric cancer. These included three retrospective cohort studies and two publications from a single RCT. Bursectomy do not appear to add the morbidity or mortality of the overall surgery. However, it did not appear to significantly improve overall survival neither in the retrospective cohort studies nor in the only RCT. The evidence to date is insufficient to suggest any additional benefit of routine bursectomy to a radical gastrectomy with D2 lymphadenectomy for gastric cancer. Results of an on-going RCT are awaited to determine if bursectomy may further improve overall survival in patients with advanced T-stage of disease. PMID:26837966

  6. URI promotes gastric cancer cell motility, survival, and resistance to adriamycin in vitro

    PubMed Central

    Hu, Xiaoxia; Zhang, Fei; Luo, Dongwei; Li, Na; Wang, Qian; Xu, Zhonghai; Bian, Huiqin; Liang, Yuting; Lu, Yaojuan; Zheng, Qiping; Gu, Junxia

    2016-01-01

    Unconventional prefoldin RPB5 interactor (URI), a RNA polymerase II Subunit 5-Interacting protein, is known to participate in the regulation of nutrient-sensitive mTOR-dependent transcription programs. Multiple studies have recently demonstrated that URI functions as an oncoprotein, possibly through the mTOR pathway, and regulates tumor cell motility, invasion, and metastasis. However, whether and how URI plays a role in gastric oncogenesis has not been elucidated. Due to drug resistance, recurrence and metastasis, the prognosis of gastric cancer remains poor. This study aims to explore the effects of URI on gastric cancer cells by focusing on their migratory ability and resistance to adriamycin. URI was over-expressed or knocked-down in MGC-803 and HGC-27 gastric cancer cells using URI plasmid or siRNA transfection approach. The cell viability, apoptosis, and migration ability were then examined by the CCK-8 assay, flow cytometer Annexin V/PI staining, and the Transwell cell migration assay respectively. The protein levels of apoptosis and EMT related genes were detected by western blot. The results showed that overexpression of URI promoted while knock-down of URI inhibited gastric cancer cell proliferation. URI overexpression resulted in increased Bcl-2 expression but decreased levels of Bax, cleaved PARP-1 and cleaved caspase-3. Conversely, cells treated with URI siRNA showed increased adriamycin induced apoptosis, along with reduced Bcl-2, but increased Bax, cleaved PARP-1 and cleaved caspase-3 expression. We have also shown that overexpression of URI enhanced cancer cell proliferation and migration with higher levels of Snail and Vimentin, whereas knockdown of URI in MGC-803 and HGC-27 cells inhibited proliferation and migration with decreased Snail and Vimentin expression. Together, our results support that URI promotes cell survival and mobility and acts as a chemotherapeutics resistant protein in MGC-803 and HGC-27 cells. URI might be a potential biomarker

  7. Syndromic Gastric Polyps: At the Crossroads of Genetic and Environmental Cancer Predisposition.

    PubMed

    Brosens, Lodewijk A A; Giardiello, Francis M; Offerhaus, G Johan; Montgomery, Elizabeth A

    2016-01-01

    Gastric polyps occur in 1-4 % of patients undergoing gastroscopy. Although most are sporadic, some gastric polyps are part of an underlying hereditary syndrome. Gastric polyps can be seen in each of the well-known gastrointestinal polyposis syndromes, but also in Lynch syndrome and in several rare not primarily gastrointestinal syndromes. In addition, Gastric Adenocarcinoma and Proximal Polyposis of the Stomach (GAPPS) is a recently described heritable syndrome characterized by isolated gastric polyposis and risk of gastric cancer.Some of these syndromes are associated with an increased risk of gastric cancer, whereas others are not. However, the neoplastic potential and the precursor status of these gastric polyps are not always clear, even in syndromes with a well-established risk of gastric cancer. For instance, the neoplastic potential of Peutz-Jeghers polyps is debatable, despite the well-established risk of gastric cancer in this syndrome. Also fundic gland polyps and gastric foveolar-type adenomas in FAP carry a low risk of malignant transformation. In contrast, gastric juvenile polyps are precursor lesions of gastric cancer in juvenile polyposis syndrome through neoplastic progression of juvenile polyps in these patients.Although these hereditary syndromes with gastric polyps are rare, recognition is important for individual patient management. Furthermore, the initiation and progression of these lesions can be influenced by environmental factors such as Helicobacter Pylori infection. This makes these rare lesions an appropriate model for understanding the clonal evolution of early gastric cancer in the wider population. PMID:27573780

  8. [A Case of Isolated Leptomeningeal Carcinomatosis from Advanced Gastric Cancer].

    PubMed

    Ji, Jung Geun; Chung, Joo Won; Nam, Seung Woo; Choi, Seung Kyu; Lee, Dong Won; Kim, Dae In; Jeon, Byung Gwan; Shin, Yun Jae

    2016-08-25

    Leptomeningeal carcinomatosis (LMC) is rare metastatic form of gastric cancer. Most cases are diagnosed in the final stage after multiple distant metastasis. An 84-year-old woman was admitted with melena, headache and vomiting. Esophagogastroduodenoscopy showed an ulceroinfiltrating lesion at the stomach (Borrmann class III), and biopsy revealed a signet ring cell carcinoma. The abdominal-pelvic CT showed no evidence of metastasis. A sudden decrease of consciousness was noted, but the brain CT showed no active lesion while the brain MRI revealed enhancement of leptomeninges. A lumbar puncture was performed and the cerebrospinal fluid study revealed malignant neoplastic cells. With family consent, no further evaluation and treatment were administered and she died six weeks after the diagnosis of gastric cancer. We report an extremely rare case of a patient who initially presented with neurologic symptoms, and was diagnosed LMC from advanced gastric cancer without any evidence of metastasis in abdomen and pelvis. PMID:27554216

  9. [Molecular targeting agents for advanced or recurrent gastric cancer patients].

    PubMed

    Fuse, Nozomu

    2012-10-01

    The combination of fluoropyrimidine and platinum with or without epirubicin or docetaxel has been regarded as standard chemotherapy for advanced or recurrent gastric cancer patients. Recently, trastuzumab with conventional chemotherapy for human epidermal growth factor receptor(HER)2 positive gastric cancer patients was proved to be effective in terms of survival benefit and has become one of standard treatment options. Other molecular target agents, such as HER1, HER2, vascular endothelial growth factor, hepatocyte growth factor/c-Met, fibroblast growth factor and mammalian target of rapamycin inhibitors were and are being evaluated in clinical trials. However, no agents other than trastuzumab have shown clear survival benefit. The predictive biomarker seems to be necessary for developing new molecular targeting agents for gastric cancer with heterogeneity.

  10. Advanced Gastric Cancer Perforation Mimicking Abdominal Wall Abscess

    PubMed Central

    Cho, Jinbeom; Park, Ilyoung; Lee, Dosang; Sung, Kiyoung; Baek, Jongmin

    2015-01-01

    Surgeons occasionally encounter a patient with a gastric cancer invading an adjacent organ, such as the pancreas, liver, or transverse colon. Although there is no established guideline for treatment of invasive gastric cancer, combined resection with radical gastrectomy is conventionally performed for curative purposes. We recently treated a patient with a large gastric cancer invading the abdominal wall, which was initially diagnosed as a simple abdominal wall abscess. Computed tomography showed that an abscess had formed adjacent to the greater curvature of the stomach. During surgery, we made an incision on the abdominal wall to drain the abscess, and performed curative total gastrectomy with partial excision of the involved abdominal wall. The patient received intensive treatment and wound management postoperatively with no surgery-related adverse events. However, the patient could not receive adjuvant chemotherapy and expired on the 82nd postoperative day. PMID:26468420

  11. JWA reverses cisplatin resistance via the CK2—XRCC1 pathway in human gastric cancer cells

    PubMed Central

    Xu, W; Chen, Q; Wang, Q; Sun, Y; Wang, S; Li, A; Xu, S; Røe, O D; Wang, M; Zhang, R; Yang, L; Zhou, J

    2014-01-01

    Gastric cancer is the third most common malignancy in China, with a median 5-year survival of only 20%. Cisplatin has been used in first-line cancer treatment for several types of cancer including gastric cancer. However, patients are often primary resistant or develop acquired resistance resulting in relapse of the cancer and reduced survival. Recently, we demonstrated that the reduced expression of base excision repair protein XRCC1 and its upstream regulator JWA in gastric cancerous tissues correlated with a significant survival benefit of adjuvant first-line platinum-based chemotherapy as well as XRCC1 playing an important role in the DNA repair of cisplatin-resistant gastric cancer cells. In the present study, we demonstrated the role of JWA in cisplatin-induced DNA lesions and aquired cisplatin resistance in five cell-culture models: gastric epithelial cells GES-1, cisplatin-sensitive gastric cancer cell lines BGC823 and SGC7901, and the cisplatin-resistant gastric cancer cell lines BGC823/DDP and SGC7901/DDP. Our results indicated that JWA is required for DNA repair following cisplatin-induced double-strand breaks (DSBs) via XRCC1 in normal gastric epithelial cells. However, in gastric cancer cells, JWA enhanced cisplatin-induced cell death through regulation of DNA damage-induced apoptosis. The protein expression of JWA was significantly decreased in cisplatin-resistant cells and contributed to cisplatin resistance. Interestingly, as JWA upregulated XRCC1 expression in normal cells, JWA downregulated XRCC1 expression through promoting the degradation of XRCC1 in cisplatin-resistant gastric cancer cells. Furthermore, the negative regulation of JWA to XRCC1 was blocked due to the mutation of 518S/519T/523T residues of XRCC1, and indicating that the CK2 activated 518S/519T/523T phosphorylation is a key point in the regulation of JWA to XRCC1. In conclusion, we report for the first time that JWA regulated cisplatin-induced DNA damage and apoptosis through the

  12. The Role of Sonic Hedgehog Reemergence During Gastric Cancer

    PubMed Central

    Martin, Jason; Donnelly, Jessica M.; Houghton, JeanMarie

    2016-01-01

    Sonic Hedgehog (Shh) signaling has been extensively studied for its role in developmental biology and cancer biology. The association between Shh and cancer development in general is well established but the functional role of Shh in the development and progression of gastric cancer specifically is largely unknown. Bone marrow-derived stem cells, specifically mesenchymal stem cells (MSCs) infiltrate and engraft into the gastric mucosa in response to the chronic inflammatory environment of Helicobacter infection. In this review, MSC infiltration and changes in the cytokine and cellular profiles of later-stage chronic environments will be tied into their interactions with the Shh pathway. We will discuss how these changes shape tumorigenesis and tumor progression in the gastric mucosa. The current review focuses on the Shh signaling pathway and its role in the development of gastric cancer, specifically in response to Helicobacter pylori infection. We follow with an in-depth discussion of the regulation of the Hedgehog pathway during acute and chronic gastric inflammation with a focus on signaling within the MSC compartment. PMID:20437100

  13. Microvessel density is a prognostic marker of human gastric cancer

    PubMed Central

    Zhao, Hong-Chuan; Qin, Rong; Chen, Xiao-Xin; Sheng, Xia; Wu, Ji-Feng; Wang, Dao-Bin; Chen, Gui-Hua

    2006-01-01

    AIM: To investigate whether microvessel density (MVD) is related with prognosis in gastric cancer patients, and the expression of cyclooxygenase-2 (COX-2) and vessel endothelial growth factor (VEGF) so as to determine the possible role of COX-2 and VEGF in gastric cancer angiogenesis. METHODS: Forty-seven formalin-fixed paraffin-embedded tissue samples of gastric cancer were evaluated for COX-2, VEGF by immunohistochemical staining. To assess tumor angiogenesis, MVD was determined by immunohistochemical staining of endothelial protein factor VIII-related antigen. The relationship among COX-2 and VEGF expression, MVD, and clinicopathologic parameters was analyzed. RESULTS: Among the 67 samples, high MVD was significantly associated with lymph node metastasis and poor survival. Multivariate survival analysis showed that MVD value and lymph node metastasis were independent prognostic factors. The expression rate of COX-2 and VEGF was significantly higher than that of the adjacent tissues. COX-2 and VEGF expression in gastric cancer was significantly correlated with tumor differentiation and depth of invasion, but not with survival. The mean MVD value of COX-2 or VEGF positive tumors was higher than that of COX-2 or VEGF negative tumors. A significant correlation was found between the expressions of COX-2 and VEGF. CONCLUSION: MVD may be one of the important prognostic factors for gastric cancer patients. COX-2 and VEGF may play an important role in tumor progression by stimulating angiogenesis. VEGF might play a main role in the COX-2 angiogenic pathway. The inhibition of angiogenesis or COX-2, VEGF activity may have an important therapeutic benefit in the control of gastric cancer. PMID:17171787

  14. Gastric tube perforation after esophagectomy for esophageal cancer.

    PubMed

    Ubukata, Hideyuki; Nakachi, Takeshi; Tabuchi, Takanobu; Nagata, Hiroyuki; Takemura, Akira; Shimazaki, Jiro; Konishi, Satoru; Tabuchi, Takafumi

    2011-05-01

    We searched for cases of perforation of the gastric tube after esophagectomy for esophageal cancer by reviewing the literature. Only 13 cases were found in the English literature, and serious complications were seen in all cases, especially in cases of posterior mediastinal reconstruction. However, in the Japanese literature serious complications were also frequently seen in retrosternal reconstruction. Gastric tubes are at a higher risk of developing an ulcer than the normal stomach, including an ulcer due to Helicobacter pylori infection, insufficient blood supply, gastric stasis, and bile juice regurgitation. H. pylori eradication and acid-suppressive medications are important preventive therapies for ordinary gastric ulcers, but for gastric tube ulcers the effects of such treatments are still controversial. We tried to determine the most appropriate treatment to avoid serious complications in the gastric tubes, but we could not confirm an optimal route because each had advantages and disadvantages. However, at least in cases with severe atrophic gastritis due to H. pylori infection or a history of frequent peptic ulcer treatment, the antesternal route is clearly the best. Many cases of gastric tube ulcers involve no pain, and vagotomy may be one of the reasons for this absence of pain. Therefore, periodic endoscopic examination may be necessary to rule out the presence of an ulcer.

  15. RABEX-5 Is Upregulated and Plays an Oncogenic Role in Gastric Cancer Development by Activating the VEGF Signaling Pathway

    PubMed Central

    Wang, Shuang; Lu, Aixia; Chen, Xiangming; Wei, Lin; Ding, Jiqiang

    2014-01-01

    RABEX-5, a guanine-nucleotide exchange factor (GEF) for RAB-5, is implicated in tumorigenesis and in the development of certain human cancers. Here, we report that RABEX-5 promotes tumor growth and the metastatic ability of gastric cancer cells both in vitro and in vivo. Expression of RABEX-5 is significantly higher in gastric cancer tissues and is associated with tumor size and lymph node metastasis. In addition, targeted silencing of RABEX-5 reduced gastric cancer cell proliferation and colony formation in vitro via the induction of a G0/G1 phase arrest, and stimulated gastric cancer cell apoptosis. Knockdown of RABEX-5 also inhibited wound healing, migration and the invasive abilities of gastric cancer cells. The results of in vivo animal experiments were also consistent with these in vitro findings. Silencing of RABEX-5 led to decreased expression of VEGF. These results indicate that RABEX-5 is upregulated and plays an oncogenic role in gastric cancer development by activating the VEGF signaling pathway. PMID:25427001

  16. Update on a tumor-associated NADH oxidase in gastric cancer cell growth

    PubMed Central

    Cheng, Hsiao-Ling; Lee, Yi-Hui; Yuan, Tein-Ming; Chen, Shi-Wen; Chueh, Pin-Ju

    2016-01-01

    Gastric cancer is one of the most common human malignancies, and its prevalence has been shown to be well-correlated with cancer-related deaths worldwide. Regrettably, the poor prognosis of this disease is mainly due to its late diagnosis at advanced stages after the cancer has already metastasized. Recent research has emphasized the identification of cancer biomarkers in the hope of diagnosing cancer early and designing targeted therapies to reverse cancer progression. One member of a family of growth-related nicotinamide adenine dinucleotide (NADH or hydroquinone) oxidases is tumor-associated NADH oxidase (tNOX; ENOX2). Unlike its counterpart CNOX (ENOX1), identified in normal rat liver plasma membranes and shown to be stimulated by growth factors and hormones, tNOX activity purified from rat hepatoma cells is constitutively active. Its activity is detectable in the sera of cancer patients but not in those of healthy volunteers, suggesting its clinical relevance. Interestingly, tNOX expression was shown to be present in an array of cancer cell lines. More importantly, inhibition of tNOX was well correlated with reduced cancer cell growth and induction of apoptosis. RNA interference targeting tNOX expression in cancer cells effectively restored non-cancerous phenotypes, further supporting the vital role of tNOX in cancer cells. Here, we review the regulatory role of tNOX in gastric cancer cell growth. PMID:26973386

  17. Treatment of esophageal-gastric double primary cancer by pedunculated remnant gastric interposition, esophageal-gastric anastomosis and gastrojejunal Billroth II anastomosis: A case report

    PubMed Central

    ZHANG, XIAO TIAN; WANG, WEI; ZHU, QIANG; CAO, MING; JIANG, ZHONG MIN; ZANG, QI

    2015-01-01

    With the continuous advancement of clinical diagnostic techniques, including imaging technology, the incidence of confirmed multiple primary cancers or double primary carcinoma increases yearly. However, studies reporting synchronization surgery performed for primary dual esophageal gastric cancer are rare. The present study reports the case of a patient with double primary esophageal-gastric cancer, located in the thoracic cavity segment of the esophagus and gastric antrum of the stomach, respectively. The gastric cancer was diagnosed by endoscopy biopsy with concomitant esophageal cancer. The patient underwent gastric cancer resection, and pedunculated remnant gastric interposition esophagogastric side anastomosis was performed with gastrojejunostomy Billroth II anastomosis behind the colon. Abdominal cavity lymph node dissection was also performed. The esophageal-gastric double primary cancer was simultaneously excised and the gastric regions were used in the construction of the upper gastrointestinal tract: The surgery was successful. However, two weeks after surgery, upper gastrointestinal imaging revealed esophagogastric anastomotic leakage. Subsequently, an esophageal stent was inserted and antibiotics and additional treatment was administered. Follow-up one year after surgery revealed that the patient was well and remained in a stable condition. PMID:26622590

  18. An Anticancer Role of Hydrogen Sulfide in Human Gastric Cancer Cells

    PubMed Central

    Qi, Qi; Yang, Jianqiang; Sun, Dongsheng; Li, Chunfeng; Xue, Yingwei; Jiang, Qiuying; Tian, Ye; Xu, Changqing; Wang, Rui

    2015-01-01

    Hydrogen sulfide (H2S) can be synthesized in mammalian cells by cystathionine γ-lyase (CSE) and/or cystathionine β-synthase (CBS). Both CSE and CBS are expressed in rat gastric tissues but their role in human gastric neoplasia has been unclear. The aims of the present study were to detect CSE and CBS proteins in human gastric cancer and determine the effect of exogenous NaHS on the proliferation of gastric cancer cells. We found that both CSE and CBS proteins were expressed in human gastric cancer cells and upregulated in human gastric carcinoma mucosa compared with those in noncancerous gastric samples. NaHS induced apoptosis of gastric cancer cells by regulating apoptosis related proteins. Also, NaHS inhibited cancer cell migration and invasion. An antigastric cancer role of H2S is thus indicated. PMID:26078811

  19. [Particular features of lymph dissection in operations for gastric cancer].

    PubMed

    Iaitskiĭ, A N; Danilov, I N

    2008-01-01

    In order to optimize the technique of lymph dissection, a method of intraoperative mapping of lymph outflow tracts was used with a lymphotropic dye Blue patente V. It allowed better orientation during lymphodissection in operations for gastric cancer. The detection and investigation of the "signal" lymph node as the most probable object of lymphogenic metastazing can improve the accuracy of postoperative staging of gastric cancer. Visualization of the lymph nodes in the preparation made it possible to increase the number of lymph nodes sent for histological investigation. PMID:18522180

  20. Long-Term Coffee Consumption and Risk of Gastric Cancer

    PubMed Central

    Zeng, Shao-Bo; Weng, Hong; Zhou, Meng; Duan, Xiao-Li; Shen, Xian-Feng; Zeng, Xian-Tao

    2015-01-01

    Abstract Association between coffee consumption and gastric cancer risk remains controversial. Hence, we performed a meta-analysis to investigate and quantify the potential dose–response association between long-term coffee consumption and risk of gastric cancer. Pertinent studies were identified by searching PubMed and Embase from January 1996 through February 10, 2015 and by reviewing the reference lists of retrieved publications. Prospective cohort studies in which authors reported effect sizes and corresponding 95% confidence intervals (CIs) of gastric cancer for 3 or more categories of coffee consumption were eligible. Results from eligible studies were aggregated using a random effect model. All analyses were carried out using the STATA 12.0 software. Nine studies involving 15 independent prospective cohorts were finally included. A total of 2019 incident cases of gastric cancer were ascertained among 1,289,314 participants with mean follow-up periods ranging from 8 to 18 years. No nonlinear relationship of coffee consumption with gastric cancer risk was indentified (P for nonlinearity = 0.53; P for heterogeneity = 0.004). The linear regression model showed that the combined relative risk (RR) of every 3 cups/day increment of total coffee consumption was 1.07 (95% CI = 0.95–1.21). Compared with the lowest category of coffee consumption, the RR of gastric cancer was 1.18 (95% CI = 0.90–1.55) for the highest (median 6.5 cups/day) category, 1.06 (95% CI = 0.85–1.32) for the second highest category (median 3.5 cups/day), and 0.97 (95% CI = 0.79–1.20) for the third highest category (median 1.5 cups/day). Subgroup analysis showed an elevated risk in the US population (RR = 1.36, 95% CI = 1.06–1.75) and no adjustment for smoking (RR = 1.67, 95% CI = 1.08–2.59) for 6.5 cups/day. Current evidence indicated there was no nonlinear association between coffee consumption and gastric cancer risk. However, high

  1. Regional but fatal: Intraperitoneal metastasis in gastric cancer.

    PubMed

    Wei, Jia; Wu, Nan-Die; Liu, Bao-Rui

    2016-09-01

    Peritoneal carcinomatosis appears to be the most common pattern of metastasis or recurrence and is associated with poor prognosis in gastric cancer patients. Many efforts have been made to improve the survival in patients with peritoneal metastasis. Hyperthermic intraperitoneal chemotherapy remains a widely accepted strategy in the treatment of peritoneal dissemination. Several phase II-III studies confirmed that the combined cytoreducitve surgery and hyperthermic intraperitoneal chemotherapy resulted in longer survival in patients with peritoneal carcinomatosis. In addition, proper selection and effective regional treatment in patients with high risk of peritoneal recurrence after resection will further improve prognosis in local advanced gastric cancer patients. PMID:27672270

  2. Regional but fatal: Intraperitoneal metastasis in gastric cancer

    PubMed Central

    Wei, Jia; Wu, Nan-Die; Liu, Bao-Rui

    2016-01-01

    Peritoneal carcinomatosis appears to be the most common pattern of metastasis or recurrence and is associated with poor prognosis in gastric cancer patients. Many efforts have been made to improve the survival in patients with peritoneal metastasis. Hyperthermic intraperitoneal chemotherapy remains a widely accepted strategy in the treatment of peritoneal dissemination. Several phase II-III studies confirmed that the combined cytoreducitve surgery and hyperthermic intraperitoneal chemotherapy resulted in longer survival in patients with peritoneal carcinomatosis. In addition, proper selection and effective regional treatment in patients with high risk of peritoneal recurrence after resection will further improve prognosis in local advanced gastric cancer patients. PMID:27672270

  3. [Particular features of lymph dissection in operations for gastric cancer].

    PubMed

    Iaitskiĭ, A N; Danilov, I N

    2008-01-01

    In order to optimize the technique of lymph dissection, a method of intraoperative mapping of lymph outflow tracts was used with a lymphotropic dye Blue patente V. It allowed better orientation during lymphodissection in operations for gastric cancer. The detection and investigation of the "signal" lymph node as the most probable object of lymphogenic metastazing can improve the accuracy of postoperative staging of gastric cancer. Visualization of the lymph nodes in the preparation made it possible to increase the number of lymph nodes sent for histological investigation.

  4. Regional but fatal: Intraperitoneal metastasis in gastric cancer

    PubMed Central

    Wei, Jia; Wu, Nan-Die; Liu, Bao-Rui

    2016-01-01

    Peritoneal carcinomatosis appears to be the most common pattern of metastasis or recurrence and is associated with poor prognosis in gastric cancer patients. Many efforts have been made to improve the survival in patients with peritoneal metastasis. Hyperthermic intraperitoneal chemotherapy remains a widely accepted strategy in the treatment of peritoneal dissemination. Several phase II-III studies confirmed that the combined cytoreducitve surgery and hyperthermic intraperitoneal chemotherapy resulted in longer survival in patients with peritoneal carcinomatosis. In addition, proper selection and effective regional treatment in patients with high risk of peritoneal recurrence after resection will further improve prognosis in local advanced gastric cancer patients.

  5. Overexpressed targeting protein for Xklp2 (TPX2) serves as a promising prognostic marker and therapeutic target for gastric cancer.

    PubMed

    Liang, Bo; Zheng, Wenjuan; Fang, Lu; Wu, Linquan; Zhou, Fan; Yin, Xiangbao; Yu, Xin; Zou, Zhenhong

    2016-08-01

    The targeting protein for Xenopus kinesin-like protein 2 (TPX2) is a putative oncogene in different human cancers. This study assessed TPX2 expression in gastric cancer tissue samples and then determined the effects of TPX2 knockdown on the regulation of gastric cancer cell malignant behaviors in vitro. Tissue samples from 115 gastric cancer patients were analyzed for TPX2 expression. The effects of TPX2 siRNA on gastric cancer cells were assessed in vitro, including cell viability, cell cycle distribution, apoptosis, migration, and invasion. The data showed that TPX2 was overexpressed in gastric cancer tissues compared to that in the adjacent normal epithelia. Moreover, TPX2 overexpression was associated with a poor overall survival and was an independent prognostic predictor of gastric cancer. In addition, the in vitro study further confirmed the ex vivo data, i.e., knockdown of TPX2 expression reduced gastric cancer cell viability but induced apoptosis and arrested cells at the G2/M phase of the cell cycle. Knockdown of TPX2 expression also inhibited the tumor cell migration and invasion capacity in vitro. At the gene level, knockdown of TPX2 expression upregulated the levels of cyclin B1, cdk4, p53, Bax, caspase-3, and E-cadherin, but downregulated the levels of cyclin D1, cdk2, N-cadherin, slug, matrix metalloprotease (MMP)-2, and MMP-9, suggesting that knockdown of TPX2 expression suppressed tumor cell epithelial-mesenchymal transition (EMT). This study demonstrated that detection of TPX2 overexpression could serve as a prognostic marker and therapeutic target for gastric cancer. PMID:27314162

  6. [Therapy of both surgical and non-surgical related complication of gastric cancer for the elderly].

    PubMed

    Li, Yong; Zheng, Jiabin

    2016-05-01

    Gastric cancer is one of the most common digestive malignant tumors. More and more elderly gastric cancer patients are diagnosed and need to undergo surgical treatment as the population ages. Since the elderly patients decrease in organ function and increase in internal diseases, the tolerance to anesthesia and surgery is poor. As a result, the incidence of surgical and postoperative complications is obviously higher. Complications can be divided into surgical complications and non-surgical related complications. Surgical complications consist mainly of hemorrhage, anastomotic leakage, anastomotic dehiscence and intestinal obstruction, while non-surgical related complications include deep venous thrombosis, pulmonary infection, anesthesia-related complication, abdominal infection, urinary infection, incision infection, poor wound healing, gastroparesis, gastroesophageal reflux disease, dumping syndrome and so on. Hence, we should consider more about the elderly patients' physical condition instead of the extent of radical operation. To reduce complications, we should evaluate the organ function and take an active role in underlying diseases before operation. Meanwhile, high quality nursing, powerful analgesia, anti-inflammation, keeping water electrolyte balance and nutrition support are also required postoperatively. Moreover, laparoscopic surgery and enhanced recovery after surgery (ERAS) can reduce the postoperative complications in elderly patients with gastric cancer as well. Further prospective randomized controlled trials about elderly gastric cancer should be carried out in the future, which can provide advanced evidences for treatment. PMID:27215514

  7. Photodynamic therapy using nanoparticle loaded with indocyanine green for experimental peritoneal dissemination of gastric cancer.

    PubMed

    Tsujimoto, Hironori; Morimoto, Yuji; Takahata, Risa; Nomura, Shinsuke; Yoshida, Kazumichi; Horiguchi, Hiroyuki; Hiraki, Shuichi; Ono, Satoshi; Miyazaki, Hiromi; Saito, Daizo; Hara, Isao; Ozeki, Eiichi; Yamamoto, Junji; Hase, Kazuo

    2014-12-01

    Although there have been multiple advances in the development of novel anticancer agents and operative procedures, prognosis of patients with advanced gastric cancer remains poor, especially in patients with peritoneal metastasis. In this study, we established nanoparticles loaded with indocyanine green (ICG) derivatives: ICG loaded lactosomes (ICGm) and investigated the diagnostic and therapeutic value of photodynamic therapy (PDT) using ICGm for experimental peritoneal dissemination of gastric cancer. Experimental peritoneal disseminated xenografts of human gastric cancer were established in nude mice. Three weeks after intraperitoneal injection of the cancer cells, either ICGm (ICGm-treated mice) or ICG solution (ICG-treated mice) was injected through the tail vein. Forty-eight hours after injection of the photosensitizer, in vivo and ex vivo imaging was carried out. For PDT, 48 h after injection of the photosensitizer, other mice were irradiated through the abdominal wall, and the body weight and survival rate were monitored. In vivo imaging revealed that peritoneal tumors were visualized through the abdominal wall in ICGm-treated mice, whereas only non-specific fluorescence was observed in ICG-treated mice. The PDT reduced the total weight of the disseminated nodules and significantly improved weight loss and survival rate in ICGm-treated mice. In conclusion, ICGm can be used as a novel diagnostic and therapeutic nanodevice in peritoneal dissemination of gastric cancer.

  8. Preclinical evidence of multiple mechanisms underlying trastuzumab resistance in gastric cancer

    PubMed Central

    Arienti, Chiara; Zanoni, Michele; Pignatta, Sara; Del Rio, Alberto; Carloni, Silvia; Tebaldi, Michela; Tedaldi, Gianluca; Tesei, Anna

    2016-01-01

    HER2-positive advanced gastric cancer patients frequently develop resistance to trastuzumab through mechanisms still poorly understood. In breast cancer, other members of the HER-family are known to be involved in trastuzumab-resistance, as is overexpression of the scaffold protein IQGAP1. In the present work, we investigated acquired resistance to trastuzumab in gastric cancer experimental models. Trastuzumab-resistant (HR) subclones derived from 3 HER2-overexpressing gastric cancer cells were generated and characterized for alterations in HER2-signaling mechanisms by next-generation sequencing, immunohistochemical, western blot and qRT-PCR techniques, and molecular modeling analysis. All subclones showed a reduced growth rate with respect to parental cell lines but each had a different resistance mechanism. In NCI N87 HR cells, characterized by a marked increase in HER2-signaling pathways with respect to the parental cell line, trastuzumab sensitivity was restored when IQGAP1 expression was silenced. AKG HR subclone showed higher HER3 protein expression than the parental line. High nuclear HER4 levels were observed in KKP HR cells. In conclusion, our study revealed that high IQGAP1 expression leads to resistance to trastuzumab in gastric cancer. Furthermore, 2 new mutations of the HER2 gene that may be involved in acquired resistance were identified in AKG HR and KKP HR subclones. PMID:26919099

  9. Emerging blood-based biomarkers for detection of gastric cancer

    PubMed Central

    Kalniņa, Zane; Meistere, Irēna; Kikuste, Ilze; Tolmanis, Ivars; Zayakin, Pawel; Linē, Aija

    2015-01-01

    Early detection and efficient monitoring of tumor dynamics are prerequisites for reducing disease burden and mortality, and for improving the management of patients with gastric cancer (GC). Blood-based biomarker assays for the detection of early-stage GC could be of great relevance both for population-wide or risk group-based screening programs, while circulating biomarkers that reflect the genetic make-up and dynamics of the tumor would allow monitoring of treatment efficacy, predict recurrences and assess the genetic heterogeneity of the tumor. Recent research to identify blood-based biomarkers of GC has resulted in the identification of a wide variety of cancer-associated molecules, including various proteins, autoantibodies against tumor associated antigens, cell-free DNA fragments, mRNAs and various non-coding RNAs, circulating tumor cells and cancer-derived extracellular vesicles. Each type of these biomarkers provides different information on the disease status, has different advantages and disadvantages, and distinct clinical usefulness. In the current review, we summarize the recent developments in blood-based GC biomarker discovery, discuss the origin of various types of biomarkers and their clinical usefulness and the technological challenges in the development of biomarker assays for clinical use. PMID:26556992

  10. The mutational burdens and evolutionary ages of early gastric cancers are comparable to those of advanced gastric cancers.

    PubMed

    Kim, Tae-Min; Jung, Seung-Hyun; Kim, Min Sung; Baek, In-Pyo; Park, Sung-Won; Lee, Sung Hak; Lee, Han Hong; Kim, Sung Soo; Chung, Yeun-Jun; Lee, Sug Hyung

    2014-11-01

    Early gastric cancers (EGCs) precede advanced gastric cancers (AGCs), with a favourable prognosis compared to AGC. To understand the progression mechanism of EGC to AGC, it is required to disclose EGC and AGC genomes in mutational and evolutionary perspectives. We performed whole-exome sequencing and copy number profiling of nine microsatellite (MS)-unstable (MSI-H) (five EGCs and four AGCs) and eight MS-stable (MSS) gastric cancers (four EGCs and four AGCs). In the cancers, we observed well-known driver mutations (TP53, APC, PIK3CA, ARID1A, and KRAS) that were enriched in cancer-related pathways, including chromatin remodelling and tyrosine kinase activity. The MSI-H genomes harboured ten times more mutations, but were largely depleted of copy number alterations (CNAs) compared to the MSS cancers. Interestingly, EGC genomes showed a comparable level of mutations to AGC in terms of the number, sequence composition, and functional consequences (potential driver mutations and affected pathways) of mutations. Furthermore, the CNAs between EGC and AGC genomes were not significantly different in either MSI-H and MSS. Evolutionary analyses using somatic mutations and MSI as molecular clocks further identified that EGC genomes were as old as AGC genomes in both MSS and MSI-H cancers. Our results suggest that the genetic makeup for gastric cancer may already be achieved in EGC genomes and that the time required for transition to AGC may be relatively short. Also, the data suggest a possibility that the mutational profiles obtained from early biopsies may be useful in the clinical settings for the molecular diagnosis and therapeutics of gastric cancer patients.

  11. Gastric cancer and coal mine dust exposure. A case-control study

    SciTech Connect

    Ames, R.G.

    1983-10-01

    Based on evidence that coal miners have elevated gastric cancer mortality rates, a case-control study was developed to assess the gastric cancer risk of coal mine dust exposure. Forty-six cases of US white male gastric cancer deaths from NIOSH coal miner cohorts were individually matched by age to controls. From these data we show that a statistically elevated gastric cancer risk exists for miners who have prolonged exposure to coal mine dust and prolonged exposure to cigarette smoke. Coal workers' pneumoconiosis, a disease defined in terms of coal dust deposition in the lungs, was not found to be a gastric cancer risk.

  12. The role of leptin in gastric cancer: Clinicopathologic features and molecular mechanisms

    SciTech Connect

    Lee, Kang Nyeong; Choi, Ho Soon; Yang, Sun Young; Park, Hyun Ki; Lee, Young Yiul; Lee, Oh Young; Yoon, Byung Chul; Hahm, Joon Soo; Paik, Seung Sam

    2014-04-18

    Highlights: • Leptin and Ob-R are expressed in gastric adenoma and early and advanced cancer. • Leptin is more likely associated with differentiated gastric cancer or cardia cancer. • Leptin proliferates gastric cancer cells via activating the STAT3 and ERK1/2 pathways. - Abstract: Obesity is associated with certain types of cancer, including gastric cancer. However, it is still unclear whether obesity-related cytokine, leptin, is implicated in gastric cancer. Therefore, we aimed to investigate the role of leptin in gastric cancer. The expression of leptin and its receptor, Ob-R, was assessed by immunohistochemical staining and was compared in patients with gastric adenoma (n = 38), early gastric cancer (EGC) (n = 38), and advanced gastric cancer (AGC) (n = 38), as a function of their clinicopathological characteristics. Gastric cancer cell lines were studied to investigate the effects of leptin on the signal transducer and activator of transcription-3 (STAT3) and extracellular receptor kinase 1/2 (ERK1/2) signaling pathways using MTT assays, immunoblotting, and inhibition studies. Leptin was expressed in gastric adenomas (42.1%), EGCs (47.4%), and AGCs (43.4%). Ob-R expression tended to increase from gastric adenoma (2%), through EGC (8%), to AGC (18%). Leptin induced the proliferation of gastric cancer cells by activating STAT3 and ERK1/2 and up-regulating the expression of vascular endothelial growth factor (VEGF). Blocking Ob-R with pharmacological inhibitors and by RNAi decreased both the leptin-induced activation of STAT3 and ERK1/2 and the leptin-induced expression of VEGF. Leptin plays a role in gastric cancer by stimulating the proliferation of gastric cancer cells via activating the STAT3 and ERK1/2 pathways.

  13. Paradoxical role of SOX2 in gastric cancer

    PubMed Central

    Carrasco-Garcia, Estefania; Santos, Juliana C; Garcia, Idoia; Brianti, Mitsue; García-Puga, Mikel; Pedrazzoli, José Jr; Matheu, Ander; Ribeiro, Marcelo L

    2016-01-01

    Sox2 is a critical regulator of embryogenesis and necessary for cellular reprogramming. It also plays an important role in tissue homeostasis and regeneration, maintaining the population of undifferentiated adult stem cells. Like various developmental and stem cell genes, SOX2 is aberrantly expressed and amplified in several human cancers. Moreover, functional studies have shown that it regulates many biological processes including cell proliferation, apoptosis, self-renewal and invasion. While it is oncogenic in most cancers, SOX2 activity is controversial in gastric cancer, where it might behave as a tumor suppressor in some situations. In this review, we discuss its role in cancer biology, with particular attention to what is known about the involvement of SOX2 in gastric cancer biology. PMID:27186426

  14. Advances in Understanding How Heavy Metal Pollution Triggers Gastric Cancer

    PubMed Central

    Yuan, Wenzhen; Yang, Ning

    2016-01-01

    With the development of industrialization and urbanization, heavy metals contamination has become a major environmental problem. Numerous investigations have revealed an association between heavy metal exposure and the incidence and mortality of gastric cancer. The mechanisms of heavy metals (lead, cadmium, mercury, chromium, and arsenic) contamination leading to gastric cancer are concluded in this review. There are four main potential mechanisms: (1) Heavy metals disrupt the gastric mucosal barrier by decreasing mucosal thickness, mucus content, and basal acid output, thereby affecting the function of E-cadherin and inducing reactive oxygen species (ROS) damage. (2) Heavy metals directly or indirectly induce ROS generation and cause gastric mucosal and DNA lesions, which subsequently alter gene regulation, signal transduction, and cell growth, ultimately leading to carcinogenesis. Exposure to heavy metals also enhances gastric cancer cell invasion and metastasis. (3) Heavy metals inhibit DNA damage repair or cause inefficient lesion repair. (4) Heavy metals may induce other gene abnormalities. In addition, heavy metals can induce the expression of proinflammatory chemokine interleukin-8 (IL-8) and microRNAs, which promotes tumorigenesis. The present review is an effort to underline the human health problem caused by heavy metal with recent development in order to garner a broader perspective. PMID:27803929

  15. Gastric cancer and the epoch of immunotherapy approaches.

    PubMed

    Niccolai, Elena; Taddei, Antonio; Prisco, Domenico; Amedei, Amedeo

    2015-05-21

    The incidence of gastric cancer (GC) fell dramatically over the last 50 years, but according to IARC-Globocan 2008, it is the third most frequent cause of cancer-related deaths with a case fatality GC ratio higher than other common malignancies. Surgical resection is the primary curative treatment for GC though the overall 5-year survival rate remains poor (approximately 20%-25%). To improve the outcome of resectable gastric cancer, different treatment strategies have been evaluated such as adjuvant or perioperative chemotherapy. In resected gastric cancer, the addition of radiotherapy to chemotherapy does not appear to provide any additional benefit. Moreover, in metastatic patients, chemotherapy is the mainstay of palliative therapy with a median overall survival of 8-10 mo and objective response rates of merely 20%-40%. Therefore, the potential for making key beneficial progress is to investigate the GC molecular biology to realize innovative therapeutic strategies, such as specific immunotherapy. In this review, we provide a panoramic view of the different immune-based strategies used for gastric cancer treatment and the results obtained in the most significant clinical trials. In detail, firstly we describe the therapeutic approaches that utilize the monoclonal antibodies while in the second part we analyze the cell-based immunotherapies.

  16. Serum biomarker panels for diagnosis of gastric cancer

    PubMed Central

    Tong, Weihua; Ye, Fei; He, Liang; Cui, Lifeng; Cui, Miao; Hu, Yuan; Li, Wei; Jiang, Jing; Zhang, David Y; Suo, Jian

    2016-01-01

    Purpose Currently, serum biomarkers that are sufficiently sensitive and specific for early detection and risk classification of gastric adenocarcinomas are not known. In this study, ten serum markers were assessed using the Luminex system and enzyme-linked immunosorbent assay for the diagnosis of gastric cancer and analysis of the relation between prognosis and metastases. Patients and methods A training set consisting of 228 gastric adenocarcinoma and 190 control samples was examined. A Luminex multiplex panel with nine biomarkers, consisting of three proteins discovered through our previous studies and six proteins previously reported to be cancer-associated, was constructed. One additional biomarker was detected using a commercial kit containing EDTA. Logistic regression, random forest (RF), and support vector machine (SVM) were used to identify the panel of discriminatory biomarkers in the training set. After selecting five proteins as candidate biomarkers, multivariate classification analyses were used to identify algorithms for diagnostic biomarker combinations. These algorithms were independently validated using a set of 57 gastric adenocarcinoma and 48 control samples. Results Serum pepsinogen I, serum pepsinogen II, A Disintegrin And Metalloproteinase domain-containing protein 8 (ADAM8), vascular endothelial growth factor (VEGF), and serum IgG to Helicobacter pylori were selected as classifiers in the three algorithms. These algorithms differentiated between the majority of gastric adenocarcinoma and control serum samples in the training/test set with high accuracy (RF 79.0%, SVM 83.8%, logistic regression 76.2%). These algorithms also differentiated the samples in the validation set (accuracy: RF 82.5%, SVM 86.1%, logistic regression 78.7%). Conclusion A panel of combinatorial biomarkers comprising VEGF, ADAM8, IgG to H. pylori, serum pepsinogen I, and pepsinogen II were developed. The use of biomarkers is a less invasive method for the diagnosis of

  17. Expression of TFF1, TFF2 and TFF3 in gastric cancer.

    PubMed

    Kirikoshi, Hiroyuki; Katoh, Masaru

    2002-09-01

    Expression of some members of the trefoil factor (TFF) and the WNT gene families is regulated together by estrogen. We have cloned and characterized human WNT signaling molecules using bioinformatics, cDNA-library screening and cDNA-PCR to investigate expression profile of WNT signaling molecules in human gastric cancer. Here, we investigated expression profile of TFF1/pS2, TFF2/SP and TFF3/ITF in human gastric cancer. Among 7 gastric cancer cell lines, TFF1 was expressed in OKAJIMA, TMK1, MKN45, and KATO-III, TFF2 in KATO-III, and TFF3 in MKN45 and KATO-III. TFFs were preferentially expressed in diffuse-type gastric cancer cell lines. Expression of TFFs in primary gastric cancer was next investigated. TFF1 was down-regulated in 7 cases out of 12 cases (58.3%) of primary gastric cancer. TFF2 was down-regulated in 10 out of 12 cases (83.3%) of primary gastric cancer. TFF3 was down-regulated in 2 out of 12 cases (16.7%) of primary gastric cancer, and was up-regulated in 5 out of 12 cases (41.7%). TFF1 and TFF2 were frequently down-regulated in primary gastric cancer, while TFF3 was up-regulated in some cases of primary gastric cancer. This is the first report on comprehensive expression analyses on TFFs in gastric cancer.

  18. miR-489 acts as a tumor suppressor in human gastric cancer by targeting PROX1

    PubMed Central

    Zhang, Bin; Ji, Sheqing; Ma, Fei; Ma, Qi; Lu, Xianzhi; Chen, Xiaobing

    2016-01-01

    Dysregulation of microRNAs (miRNAs) are linked to tumorigenesis and tumor progression. In this study, we examined the expression of miR-489 in gastric cancer tissues and cells. Loss- and gain-of-function experiments were done to determine the roles of miR-489 in gastric cancer cell proliferation and invasion. Bioinformatic prediction, luciferase reporter assays, and Western blot analysis were employed to identify the target gene(s) of miR-489. We found that miR-489 was significantly (P < 0.05) downregulated in human gastric cancer tissues and cell lines, compared to their non-malignant counterparts. Enforced expression of miR-489 significantly suppressed gastric cancer cell proliferation and invasion, while miR-489 knockdown enhanced the aggressive behaviors of gastric cancer cells. Prospero homeobox 1 (PROX1) was identified to be a direct target of miR-489. A significant negative correlation was seen between miR-489 and PROX1 protein expression in gastric cancer tissues (r = -0.462, P = 0.023). Silencing of PROX1 phenocopied the suppressive effects of miR-489 in gastric cancer cells. Rescue experiments demonstrated that overexpression of a miR-489-resistant form of PROX1 significantly prevented the reduction in cell proliferation and invasion induced by miR-489 overexpression. In vivo studies confirmed that miR-489 overexpression retarded the growth of xenograft tumors, which was accompanied by reduced PROX1 expression. Overall, these data provide evidence for the suppressive activity of miR-489 in gastric cancer, which is ascribed to targeting of PROX1. The miR-489/PROX1 axis may represent a potential therapeutic target for this disease. PMID:27725907

  19. Endoscopic Submucosal Dissection of an Inverted Early Gastric Cancer-Forming False Gastric Diverticulum

    PubMed Central

    Lee, Yong-il; Lee, Sang-kil

    2016-01-01

    Endoscopic submucosal dissection (ESD) is a standard treatment for early gastric cancer (EGC) that does not have any risk of lymph node or distant metastases. Here, we report a case of EGC resembling a diverticulum. Diverticular formation makes it difficult for endoscopists to determine the depth of invasion and to subsequently perform ESD. Because the false diverticulum does not have a muscular layer, this lesion can be treated with ESD. Our case was successfully treated with ESD. After ESD, the EGC was confined to the submucosal layer without vertical and lateral margin involvement. This is the first case in which ESD was successfully performed for a case of EGC that coexisted with a false gastric diverticulum. An additional, larger study is needed to determine the efficacy of ESD in various types of EGC, such as a false gastric diverticulum. PMID:26855930

  20. Biomarkers for antitumor activity of bevacizumab in gastric cancer models

    PubMed Central

    2012-01-01

    Background Bevacizumab is a humanized monoclonal antibody to human vascular endothelial cell growth factor (VEGF) and has been used for many types of cancers such as colorectal cancer, non-small cell lung cancer, breast cancer, and glioblastoma. Bevacizumab might be effective against gastric cancer, because VEGF has been reported to be involved in the development of gastric cancer as well as other cancers. On the other hand, there are no established biomarkers to predict the bevacizumab efficacy in spite of clinical needs. Therefore, we tried to identify the predictive markers for efficacy of bevacizumab in gastric cancer patients by using bevacizumab-sensitive and insensitive tumor models. Methods Nine human gastric and two colorectal cancer mouse xenografts were examined for their sensitivity to bevacizumab. We examined expression levels of angiogenic factors by ELISA, bioactivity of VEGF by phosphorylation of VEGFR2 in HUVEC after addition of tumor homogenate, tumor microvessel density by CD31-immunostaining, and polymorphisms of the VEGF gene by HybriProbe™ assay. Results Of the 9 human gastric cancer xenograft models used, GXF97, MKN-45, MKN-28, 4-1ST, SC-08-JCK, and SC-09-JCK were bevacizumab-sensitive, whereas SCH, SC-10-JCK, and NCI-N87 were insensitive. The sensitivity of the gastric cancer model to bevacizumab was not related to histological type or HER2 status. All tumors with high levels of VEGF were bevacizumab-sensitive except for one, SC-10-JCK, which had high levels of VEGF. The reason for the refractoriness was non-bioactivity on the phosphorylation of VEGFR2 and micro-vessel formation of VEGF, but was not explained by the VEGF allele or VEGF165b. We also examined the expression levels of other angiogenic factors in the 11 gastrointestinal tumor tissues. In the refractory models including SC-10-JCK, tumor levels of another angiogenic factor, bFGF, were relatively high. The VEGF/bFGF ratio correlated more closely with sensitivity to bevacizumab

  1. Gastric Bypass Reduces Symptoms and Hormonal Responses in Hypoglycemia.

    PubMed

    Abrahamsson, Niclas; Börjesson, Joey Lau; Sundbom, Magnus; Wiklund, Urban; Karlsson, F Anders; Eriksson, Jan W

    2016-09-01

    Gastric bypass (GBP) surgery, one of the most common bariatric procedures, induces weight loss and metabolic effects. The mechanisms are not fully understood, but reduced food intake and effects on gastrointestinal hormones are thought to contribute. We recently observed that GBP patients have lowered glucose levels and frequent asymptomatic hypoglycemic episodes. Here, we subjected patients before and after undergoing GBP surgery to hypoglycemia and examined symptoms and hormonal and autonomic nerve responses. Twelve obese patients without diabetes (8 women, mean age 43.1 years [SD 10.8] and BMI 40.6 kg/m(2) [SD 3.1]) were examined before and 23 weeks (range 19-25) after GBP surgery with hyperinsulinemic-hypoglycemic clamp (stepwise to plasma glucose 2.7 mmol/L). The mean change in Edinburgh Hypoglycemia Score during clamp was attenuated from 10.7 (6.4) before surgery to 5.2 (4.9) after surgery. There were also marked postsurgery reductions in levels of glucagon, cortisol, and catecholamine and the sympathetic nerve responses to hypoglycemia. In addition, growth hormone displayed a delayed response but to a higher peak level. Levels of glucagon-like peptide 1 and gastric inhibitory polypeptide rose during hypoglycemia but rose less postsurgery compared with presurgery. Thus, GBP surgery causes a resetting of glucose homeostasis, which reduces symptoms and neurohormonal responses to hypoglycemia. Further studies should address the underlying mechanisms as well as their impact on the overall metabolic effects of GBP surgery.

  2. Change in gastric emptying eight weeks after endoscopic submucosal dissection in patients with early gastric cancer

    PubMed Central

    Watanabe, Ko; Hikichi, Takuto; Sato, Masaki; Nakamura, Jun; Obara, Katsutoshi; Ohira, Hiromasa

    2016-01-01

    Background: Gastric emptying after endoscopic submucosal dissection (ESD) for early gastric cancer is not clear. The aim of this study was to evaluate changes in gastric emptying from before ESD to 8 weeks after ESD. Methods: In total, 54 patients with early gastric cancer were enrolled in this study. A breath test with carbon 13 (13C) was conducted before ESD and at 1 and 8 weeks after ESD. The Tlag and T1/2 values were analyzed at each time point. The primary outcomes were the changes in the Tlag and T1/2 values from before ESD to 1 and 8 weeks after ESD. The secondary outcomes were the factors associated with the changes in the Tlag and T1/2 values. Results: Gastric emptying was delayed at 1 and 8 weeks after ESD compared with before ESD (Tlag P = 0.002, P < 0.001; T1/2 P = 0.005, P = 0.001, respectively). The changes in the Tlag and T1/2 values from before ESD to 1 week after ESD were greater for proximal stomach lesions than for distal stomach lesions (P = 0.028, P < 0.001). Proximal stomach lesions were identified as the significant factor that influenced changes in the Tlag and T1/2 values from before ESD to 1 week after ESD in the multivariate analyses (Tlag P = 0.003, T1/2 P = 0.005). Conclusions: ESD induced delayed gastric emptying until 8 weeks after ESD. Proximal stomach lesions were also associated with decreased emptying 1 week after ESD. PMID:27227121

  3. [Research advances of K-ras mutation in the prognosis and targeted therapy of gastric cancer].

    PubMed

    Huang, Y; Wei, J; Liu, B R

    2016-02-01

    K-ras mutations have been described in 30% of human cancers with significantly different mutation frequencies. High K-ras mutation frequency is found in many cancers such as pancreas and lung cancers, whereas, gastric cancer has a relatively low K-ras mutation frequency. In recent years, numerous researches have focused on the K-ras mutation in gastric cancer. This review summarizes the K-ras mutation frequency in gastric cancer, the relationship of K-ras mutation with clinicopathologic features and prognosis of gastric cancer patients, targeted therapy for K-ras mutated gastric cancer, some small-molecular inhibitors of K-ras, and development of targeted therapy drugs for K-ras signaling pathway in gastric cancer.

  4. Evaluation of rational extent lymphadenectomy for local advanced gastric cancer

    PubMed Central

    Liang, Han; Deng, Jingyu

    2016-01-01

    Based upon studies from randomized clinical trials, the extended (D2) lymph node dissection is now recommended as a standard procedure for local advanced gastric cancer worldwide. However, the rational extent lymphadenectomy for local advanced gastric cancer has remained a topic of debate in the past decades. Due to the limitation of low metastatic rate in para-aortic nodes (PAN) in JCOG9501, the clinical benefit of D2+ para-aortic nodal dissection (PAND) for patients with stage T4 and/or stage N3 disease, which is very common in China and other countries except Japan and Korea, cannot be determined. Furthermore, the role of splenectomy for complete resection of No.10 and No.11 nodes has been controversial, and however, the final results from the randomized trial of JCOG0110 have yet to be completed. Gastric cancer with the No.14 and No.13 lymph node metastasis is defined as M1 stage in the current version of the Japanese classification. We propose that D2+No.14v and +No.13 lymphadenectomy may be an option in a potentially curative gastrectomy for tumors with apparent metastasis to the No.6 nodes or infiltrate to duodenum. The examined lymph node and extranodal metastasis are significantly associated with the survival of gastric cancer patients. PMID:27647967

  5. Influence of obesity and bariatric surgery on gastric cancer.

    PubMed

    Dantas, Anna Carolina Batista; Santo, Marco Aurelio; de Cleva, Roberto; Sallum, Rubens Antônio Aissar; Cecconello, Ivan

    2016-06-01

    Esophageal and gastric cancer (GC) are related to obesity and bariatric surgery. Risk factors, such as gastroesophageal reflux and Helicobacter pylori, must be investigated and treated in obese population. After surgery, GC reports are anecdotal and treatment is not standardized. This review aims to discuss GC related to obesity before and after bariatric surgery. PMID:27458534

  6. Evaluation of rational extent lymphadenectomy for local advanced gastric cancer.

    PubMed

    Liang, Han; Deng, Jingyu

    2016-08-01

    Based upon studies from randomized clinical trials, the extended (D2) lymph node dissection is now recommended as a standard procedure for local advanced gastric cancer worldwide. However, the rational extent lymphadenectomy for local advanced gastric cancer has remained a topic of debate in the past decades. Due to the limitation of low metastatic rate in para-aortic nodes (PAN) in JCOG9501, the clinical benefit of D2+ para-aortic nodal dissection (PAND) for patients with stage T4 and/or stage N3 disease, which is very common in China and other countries except Japan and Korea, cannot be determined. Furthermore, the role of splenectomy for complete resection of No.10 and No.11 nodes has been controversial, and however, the final results from the randomized trial of JCOG0110 have yet to be completed. Gastric cancer with the No.14 and No.13 lymph node metastasis is defined as M1 stage in the current version of the Japanese classification. We propose that D2+No.14v and +No.13 lymphadenectomy may be an option in a potentially curative gastrectomy for tumors with apparent metastasis to the No.6 nodes or infiltrate to duodenum. The examined lymph node and extranodal metastasis are significantly associated with the survival of gastric cancer patients. PMID:27647967

  7. Variations of Tongue Coating Microbiota in Patients with Gastric Cancer.

    PubMed

    Hu, Jie; Han, Shuwen; Chen, Yan; Ji, Zhaoning

    2015-01-01

    The physical status of humans can be estimated by observing the appearance of the tongue coating, known as tongue diagnosis. The goals of this study were to reveal the relationship between tongue coating appearance and the oral microbiota in patients with gastric cancer and to open a novel research direction supporting tongue diagnosis. We used a tongue manifestation acquisition instrument to analyse the thickness of the tongue coating of patients with gastric cancer and that of healthy controls, and high-throughput sequencing was used to describe the microbial community of the tongue coating by sequencing the V2-V4 region of the 16S rDNA. The tongue coatings of 74 patients with gastric cancer were significantly thicker than those of 72 healthy controls (343.11 ± 198.22 versus 98.42 ± 48.25, P < 0.001); 51.35% of the patients were assessed as having thick tongue coatings, whereas all healthy controls were assessed as having thin tongue coatings. Thick tongue coatings presented lower microbial community diversity than thin tongue coatings. The tongue coating bacterial community is associated with the appearance of the tongue coating. The tongue coating may be a potential source for diagnosing gastric cancer, but its sensitivity needs to be further improved.

  8. The Japanese Viewpoint on the Histopathology of Early Gastric Cancer.

    PubMed

    Sekine, Shigeki; Yoshida, Hiroshi; Jansen, Marnix; Kushima, Ryoji

    2016-01-01

    Japanese histopathologists have traditionally had greater opportunity to study the histology and clinical course of early gastric cancer because of technological developments including double contrast radiography and endoscopy systems, combined with the higher incidence of gastric cancer in the general population in Japan. Endoscopic resection is now considered best practice for treatment of early gastric cancers with a negligible risk of lymph node metastasis. Histopathologic evaluation plays a critical role in assessing the likelihood of lymph node metastasis on endoscopically resected specimens. There remains disparity between Western and Japanese histopathologists in the conceptual approach to the histopathologic evaluation of neoplastic lesions in the upper gastrointestinal tract, in particular regarding lesions straddling the borderline between noninvasive and invasive disease. Although in routine practice, the clinical impact of these conceptual differences is small, this disparity does complicate international exchange of datasets and the development of globally applicable formal definitions. Here we review the current practice in histological diagnosis of early gastric cancer in Japan and discuss some of the conceptual differences between Japanese and Western histopathological assessment of lesions in the neoplastic stomach. PMID:27573779

  9. Electronic Endoscopy in Endoscopic Mucosal Resection (EMR) of Gastric Cancer

    PubMed Central

    Misaka, Ryouichi; Yamada, Michiru; Midorikawa, Shouko; Sanji, Tetuya; Shinohara, Satoshi; Morita, Shigefumi; Handa, Yutaka; Ohno, Hiroyuki; Saitou, Yasuhiko; Yosida, Hajime; Takase, Masahisa; Saitou, Toshihiko

    1995-01-01

    The role in which electronic endoscopy plays is important in EMR. It is useful in diagnosis and treatment of gastric cancer from a clinical viewpoint. EMR with use of electronic endoscopy allows better coordination between the operator and assistants, and thus improves the results further. PMID:18493367

  10. Screening Driving Transcription Factors in the Processing of Gastric Cancer

    PubMed Central

    Xu, Guangzhong; Li, Kai; Zhang, Nengwei; Zhu, Bin; Feng, Guosheng

    2016-01-01

    Background. Construction of the transcriptional regulatory network can provide additional clues on the regulatory mechanisms and therapeutic applications in gastric cancer. Methods. Gene expression profiles of gastric cancer were downloaded from GEO database for integrated analysis. All of DEGs were analyzed by GO enrichment and KEGG pathway enrichment. Transcription factors were further identified and then a global transcriptional regulatory network was constructed. Results. By integrated analysis of the six eligible datasets (340 cases and 43 controls), a bunch of 2327 DEGs were identified, including 2100 upregulated and 227 downregulated DEGs. Functional enrichment analysis of DEGs showed that digestion was a significantly enriched GO term for biological process. Moreover, there were two important enriched KEGG pathways: cell cycle and homologous recombination. Furthermore, a total of 70 differentially expressed TFs were identified and the transcriptional regulatory network was constructed, which consisted of 566 TF-target interactions. The top ten TFs regulating most downstream target genes were BRCA1, ARID3A, EHF, SOX10, ZNF263, FOXL1, FEV, GATA3, FOXC1, and FOXD1. Most of them were involved in the carcinogenesis of gastric cancer. Conclusion. The transcriptional regulatory network can help researchers to further clarify the underlying regulatory mechanisms of gastric cancer tumorigenesis. PMID:27403158

  11. Current status of robotic gastrectomy for gastric cancer.

    PubMed

    Obama, Kazutaka; Sakai, Yoshiharu

    2016-05-01

    Although over 3000 da Vinci Surgical System (DVSS) devices have been installed worldwide, robotic surgery for gastric cancer has not yet become widely spread and is only available in several advanced institutions. This is because, at least in part, the advantages of robotic surgery for gastric cancer remain unclear. The safety and feasibility of robotic gastrectomy have been demonstrated in several retrospective studies. However, no sound evidence has been reported to support the superiority of a robotic approach for gastric cancer treatment. In addition, the long-term clinical outcomes following robotic gastrectomy have yet to be clarified. Nevertheless, a robotic approach can potentially overcome the disadvantages of conventional laparoscopic surgery if the advantageous functions of this technique are optimized, such as the use of wristed instruments, tremor filtering and high-resolution 3-D images. The potential advantages of robotic gastrectomy have been discussed in several retrospective studies, including the ability to achieve sufficient lymphadenectomy in the area of the splenic hilum, reductions in local complication rates and a shorter learning curve for the robotic approach compared to conventional laparoscopic gastrectomy. In this review, we present the current status and discuss issues regarding robotic gastrectomy for gastric cancer.

  12. Influence of obesity and bariatric surgery on gastric cancer

    PubMed Central

    Dantas, Anna Carolina Batista; Santo, Marco Aurelio; de Cleva, Roberto; Sallum, Rubens Antônio Aissar; Cecconello, Ivan

    2016-01-01

    Esophageal and gastric cancer (GC) are related to obesity and bariatric surgery. Risk factors, such as gastroesophageal reflux and Helicobacter pylori, must be investigated and treated in obese population. After surgery, GC reports are anecdotal and treatment is not standardized. This review aims to discuss GC related to obesity before and after bariatric surgery. PMID:27458534

  13. Clinical significance of lymphadenectomy in patients with gastric cancer.

    PubMed

    Tóth, Dezső; Plósz, János; Török, Miklós

    2016-02-15

    Approximately thirty percent of patients with gastric cancer undergo an avoidable lymph node dissection with a higher rate of postoperative complication. Comparing the D1 and D2 dissections, it was found that there is a significant difference in morbidity, favoured D1 dissection without any difference in overall survival. Subgroup analysis of patients with T3 tumor shows a survival difference favoring D2 lymphadenectomy, and there is a better gastric cancer-related death and non-statistically significant improvement of survival for node-positive disease in patients with D2 dissection. However, the extended lymphadenectomy could improve stage-specific survival owing to the stage migration phenomenon. The deployment of centralization and application of national guidelines could improve the surgical outcomes. The Japanese and European guidelines enclose the D2 lymphadenectomy as the gold standard in R0 resection. In the individualized, stage-adapted gastric cancer surgery the Maruyama computer program (MCP) can estimate lymph node involvement preoperatively with high accuracy and in addition the Maruyama Index less than 5 has a better impact on survival, than D-level guided surgery. For these reasons, the preoperative application of MCP is recommended routinely, with an aim to perform "low Maruyama Index surgery". The sentinel lymph node biopsy (SNB) may decrease the number of redundant lymphadenectomy intraoperatively with a high detection rate (93.7%) and an accuracy of 92%. More accurate stage-adapted surgery could be performed using the MCP and SNB in parallel fashion in gastric cancer.

  14. Microsatellite instability and loss of heterozygosity in gastric cancer

    SciTech Connect

    Schneider, B.G.; Pulitzer, D.R.; Moehlmann, R.D.

    1994-09-01

    In order to detect regions of DNA containing tumor suppressor genes involved in the development of gastric cancer, we evaluated loss of heterozygosity (LOH) in 78 gastric adenocarcinomas. A total of 46 microsatellite markers were employed, which detected at least one site per arm of each autosome in the human genome, including several markers linked to known tumor suppressor genes (TP53, APC, DCC, RB1, and BRCA1). We detected elevated rates of LOH at D3S1478 on chromosome 3p21 (44%, or 22 of 50 cases), at D12S78 at 12q14q24.33 (39%), and 37% at D9S157 on 9p, three sites not previously known to be affected in gastric cancer. Another locus on chromosome 12q, D12S97, showed LOH in 40% of informative cases. LOH was detected on chromosome 17p near TP53 in 66% of informative cases (23 of 35). Microsatellite instability (MI) was observed in 22% of the cancers. Tumors varied greatly in percentage of sites exhibiting MI, from 0% to 77% of sites tested. These findings expand the description of the genetic lesions occurring in gastric cancer.

  15. Requirement for a standardised definition of advanced gastric cancer

    PubMed Central

    DE SOL, ANGELO; TRASTULLI, STEFANO; GRASSI, VERONICA; CORSI, ALESSIA; BARILLARO, IVAN; BOCCOLINI, ANDREA; DI PATRIZI, MICOL SOLE; DI ROCCO, GIORGIO; SANTORO, ALBERTO; CIROCCHI, ROBERTO; BOSELLI, CARLO; REDLER, ADRIANO; NOYA, GIUSEPPE; KONG, SEONG-HO

    2014-01-01

    Each year, ~988,000 new cases of stomach cancer are reported worldwide. Uniformity for the definition of advanced gastric cancer (AGC) is required to ensure the improved management of patients. Various classifications do actually exist for gastric cancer, but the classification determined by lesion depth is extremely important, as it has been shown to correlate with patient prognosis; for example, early gastric cancer (EGC) has a favourable prognosis when compared with AGC. In the literature, the definition of EGC is clear, however, there is heterogeneity in the definition of AGC. In the current study, all parameters of the TNM classification for AGC reported in each previous study were individually analysed. It was necessary to perform a comprehensive systematic literature search of all previous studies that have reported a definition of ACG to guarantee homogeneity in the assessment of surgical outcome. It must be understood that the term ‘advanced gastric cancer’ may implicate a number of stages of disease, and studies must highlight the exact clinical TNM stages used for evaluation of the study. PMID:24348842

  16. [Knockdown of Drosha promotes chemosensitivity of epirubicin for gastric cancer MGC-803 cells].

    PubMed

    Xu, Liyun; Chen, Yanlin; Wen, Siyang; DU, Yan'e; Tang, Xi; Liu, Manran

    2016-09-01

    Objective To establish a gastric cancer cell line with stable Drosha silenced and explore the effect of Drosha on the chemosensitivity of gastric cancer cells to epirubicin. Methods Interfering sequences targeting Drosha were designed and inserted into the lentiviral vectors, which were used to transfect MGC-803 cells. The level of Drosha mRNA was detected by quantitative real-time PCR; Drosha protein was detected by Western blotting; MTT assay was performed to test the 50% inhibitory concentration (IC50) of epirubicin agaisnt wide-type MGC-803 cells. After the treatment with IC50 epirubicin, the apoptosis rate of each cell group was determined by flow cytometry; the expressions of apoptosis-related proteins caspase-3, caspase-9, Bax, Bcl-2 were assessed by Western blotting. Results The gastric cancer MGC-803 cells with stable Drosha silenced were successfully established, and the levels of Drosha mRNA and protein were reduced. After the cells were treated with 0.5 mg/L(IC50) epirubicin, the apoptosis rate of MGC-803 cells was raised, the protein expressions of caspase-3 , caspase-9 and Bax were significantly upregulated and Bcl-2 was downregulated. Conclusion The silence of Drosha expression can promote the sensitivity of gastric cancer to epirubicin. PMID:27609577

  17. Nutritional Care of Gastric Cancer Patients with Clinical Outcomes and Complications: A Review

    PubMed Central

    Choi, Wook Jin

    2016-01-01

    The incidence and mortality of gastric cancer have been steadily decreased over the past few decades. However, gastric cancer is still one of the leading causes of cancer deaths across many regions of the world, particularly in Asian countries. In previous studies, nutrition has been considered one of significant risk factors in gastric cancer patients. Especially, malnourished patients are at greater risk of adverse clinical outcomes (e.g., longer hospital stay) and higher incidence of complications (e.g., wound/infectious complications) compared to well-nourished patients. Malnutrition is commonly found in advanced gastric cancer patients due to poor absorption of essential nutrients after surgery. Therefore, nutritional support protocols, such as early oral and enternal feeding, have been proposed in many studies, to improve unfavorable clinical outcomes and to reduce complications due to delayed application of oral nutritional support or parental feeding. Also, the supplied with enternal immune-enriched diet had more benefits in improving clinical outcomes and fewer complications compared to a group supplied with control formula. Using nutritional screening tools, such as nutritional risk index (NRI) and nutritional risk screening (NRS 2002), malnourished patients showed higher incidence of complications and lower survival rates than non-malnourished patients. However, a long-term nutritional intervention, such as nutritional counseling, was not effective in the patients. Therefore, early assessment of nutritional status in patients using a proper nutritional screening tool is suggested to prevent malnutrition and adverse health outcomes. Further studies with numerous ethnic groups may provide stronger scientific evidences in association between nutritional care and recovery from surgery in patients with gastric cancer. PMID:27152296

  18. Phylogeographic Origin of Helicobacter pylori Is a Determinant of Gastric Cancer Risk

    PubMed Central

    de Sablet, Thibaut; Piazuelo, M. Blanca; Shaffer, Carrie L.; Schneider, Barbara G.; Asim, Mohammad; Chaturvedi, Rupesh; Bravo, Luis E.; Sicinschi, Liviu A.; Delgado, Alberto G.; Mera, Robertino M.; Israel, Dawn A.; Romero-Gallo, Judith; Peek, Richard M.; Cover, Timothy L.; Correa, Pelayo; Wilson, Keith T.

    2011-01-01

    Background and Aims Helicobacter pylori colonises the stomach in half of all humans, and is the principal cause of gastric cancer, the second leading cause of cancer death worldwide. While gastric cancer rates correlate with H. pylori prevalence in some areas, there are regions where infection is nearly universal, but rates of gastric cancer are low. In the case of Colombia, there is a 25-fold increase in gastric cancer rate in the Andean mountain (high risk) region compared to the coastal (low risk) region, despite similarly high (~90%) H. pylori prevalence in the two locations. Our aim was to investigate the ancestral origin of H. pylori strains isolated from subjects in these high and low risk regions and to determine whether this is a predictive determinant of precancerous lesions. Methods Multi-locus sequence typing was used to investigate phylogeographic origins of infecting H. pylori strains isolated from subjects in the Pacific coast and Andean mountains in the state of Nariño, Colombia. We analysed 64 subjects infected with cagA+ vacA s1m1 strains. Gastric biopsy slides from each individual were scored for histologic lesions and evaluated for DNA damage by immunohistochemistry. Results We show that strains from the high risk region were all of European phylogeographic origin, whereas those from the low risk region were of either European (34%) or African origin (66%). European strain origin was strongly predictive of increased premalignant histologic lesions and epithelial DNA damage, even in the low risk region; African strain origin was associated with reduced severity of these parameters. Conclusion The phylogeographic origin of H. pylori strains provides an explanation for geographic differences in cancer risk deriving from this infection. PMID:21357593

  19. Clinical implication of 14-3-3 epsilon expression in gastric cancer

    PubMed Central

    Leal, Mariana Ferreira; Calcagno, Danielle Queiroz; Demachki, Sâmia; Assumpção, Paulo Pimentel; Chammas, Roger; Burbano, Rommel Rodríguez; Smith, Marília de Arruda Cardoso

    2012-01-01

    AIM: To evaluate for the first time the protein and mRNA expression of 14-3-3ε in gastric carcinogenesis. METHODS: 14-3-3ε protein expression was determined by western blotting, and mRNA expression was examined by real-time quantitative RT-PCR in gastric tumors and their matched non-neoplastic gastric tissue samples. RESULTS: Authors observed a significant reduction of 14-3-3ε protein expression in gastric cancer (GC) samples compared to their matched non-neoplastic tissue. Reduced levels of 14-3-3ε were also associated with diffuse-type GC and early-onset of this pathology. Our data suggest that reduced 14-3-3ε may have a role in gastric carcinogenesis process. CONCLUSION: Our results reveal that the reduced 14-3-3ε expression in GC and investigation of 14-3-3ε interaction partners may help to elucidate the carcinogenesis process. PMID:22509086

  20. Noncoding Genomics in Gastric Cancer and the Gastric Precancerous Cascade: Pathogenesis and Biomarkers

    PubMed Central

    Sandoval-Bórquez, Alejandra; Saavedra, Kathleen; Carrasco-Avino, Gonzalo; Garcia-Bloj, Benjamin; Fry, Jacqueline; Wichmann, Ignacio; Corvalán, Alejandro H.

    2015-01-01

    Gastric cancer is the fifth most common cancer and the third leading cause of cancer-related death, whose patterns vary among geographical regions and ethnicities. It is a multifactorial disease, and its development depends on infection by Helicobacter pylori (H. pylori) and Epstein-Barr virus (EBV), host genetic factors, and environmental factors. The heterogeneity of the disease has begun to be unraveled by a comprehensive mutational evaluation of primary tumors. The low-abundance of mutations suggests that other mechanisms participate in the evolution of the disease, such as those found through analyses of noncoding genomics. Noncoding genomics includes single nucleotide polymorphisms (SNPs), regulation of gene expression through DNA methylation of promoter sites, miRNAs, other noncoding RNAs in regulatory regions, and other topics. These processes and molecules ultimately control gene expression. Potential biomarkers are appearing from analyses of noncoding genomics. This review focuses on noncoding genomics and potential biomarkers in the context of gastric cancer and the gastric precancerous cascade. PMID:26379360

  1. A Phase I Study of LJM716 in Squamous Cell Carcinoma of Head and Neck, or HER2+ Breast Cancer or Gastric Cancer

    ClinicalTrials.gov

    2014-04-21

    HER2 + Breast Cancer, HER2 + Gastric Cancer, Squamous Cell Carcinoma of Head and Neck, Esophageal Squamous Cell Carcinoma; HER2 + Breast Cancer; HER2 + Gastric Cancer; Squamous Cell Carcinoma of Head and Neck; Esophageal Squamous Cell Carcinoma

  2. Downregulation of ADAMTS8 by DNA Hypermethylation in Gastric Cancer and Its Clinical Significance

    PubMed Central

    Zhang, Jiakui; Li, Xin; Zhang, Chundong; Zhang, Hongbin; Jin, Junzhe; Dai, Dongqiu

    2016-01-01

    A disintegrin and metallopeptidase with thrombospondin motif type 8 (ADAMTS8), a member of the ADAMTS family, was discovered as a novel angiogenesis inhibitor. We analyzed the expression and methylation of ADAMTS8 in primary gastric tumors and gastric cancer cell lines. We also examined the relationship between ADAMTS8 expression and methylation and clinicopathologic features. The results showed that the significant downregulation of ADAMTS8 mRNA expression was observed in gastric cancer cell lines and tissues, and its expression was related to invasive depth and lymph node metastasis. CpG was hypermethylated in gastric cancer cell lines MKN45, MGC803, and BGC823, as well as primary gastric cancer specimens. ADAMTS8 mRNA expression was significantly lower in methylated primary gastric tumors. A significant association was found between ADAMTS8 methylation status and lymph node metastasis in primary gastric cancer. Moreover, ADAMTS8 expression was upregulated in the gastric cancer cell lines MGC803, BGC823, and MKN45 after treatment with 5-aza-2′-deoxycytidine. Thus, our results demonstrate that expression of ADAMTS8 mRNA is significantly decreased and DNA methylation is frequent in gastric cancer. ADAMTS8 hypermethylation is associated with decreased expression in gastric cancer and may play an important role in the invasion and metastasis of gastric cancer. PMID:27493958

  3. Helicobacter pylori infection and chronic gastritis in gastric cancer.

    PubMed Central

    Sipponen, P.; Kosunen, T. U.; Valle, J.; Riihelä, M.; Seppälä, K.

    1992-01-01

    AIMS: To investigate the prevalence of Helicobacter pylori associated chronic gastritis in patients with gastric cancer. METHODS: Serum IgG antibodies for H pylori were determined in 54 consecutive patients with gastric carcinoma. The prevalence of H pylori in gastric mucosa was also examined histologically (modified Giemsa) in 32 patients from whom adequate biopsy specimens of the antrum and corpus were available. Thirty five patients with gastrointestinal tumours outside the stomach and 48 with non-gastrointestinal malignancies served as controls. RESULTS: Of the 54 patients, 38 (70%) had H pylori antibodies (IgG) in their serum (three additional patients had H pylori antibodies IgA, class specific but not IgG specific). This prevalence was significantly higher (p less than 0.05) than that (49%) in the 35 controls. No differences in prevalence of H pylori antibodies were found between gastric cancer cases of intestinal (IGCA) or diffuse (DGCA) type, both these types showing H pylori antibodies (IgG) in 71% of the patients. In the subgroup of 32 subjects, five patients had normal gastric mucosa and four showed corpus limited atrophy ("pernicious anaemia type" atrophy of type A). All of these nine patients had no evidence of current or previous H pylori infection in serum (no IgG antibodies) or in tissue sections (negative Giemsa staining). The remaining 23 patients had antral or pangastritis, and all had evidence of current or previous H pylori infection. CONCLUSIONS: H pylori associated chronic gastritis was the associated disease in 75% of the patients with gastric cancer occurring equally often in both IGCA and DGCA groups. About 25% of cases seem to have a normal stomach or severe corpus limited atrophy, neither of which showed evidence of concomitant H pylori infection. PMID:1577969

  4. NDRG1 expression is related to the progression and prognosis of gastric cancer patients through modulating proliferation, invasion and cell cycle of gastric cancer cells.

    PubMed

    Chang, Xiaojing; Xu, Xiaoyang; Ma, Jinguo; Xue, Xiaoying; Li, Zhenhua; Deng, Peng; Zhang, Shuanglong; Zhi, Yu; Chen, Jing; Dai, Dongqiu

    2014-09-01

    N-myc downstream-regulated gene 1 (NDRG1) has been proposed as a tumor suppressor gene in many different types of tumors, but its potential function and corresponding mechanism are not yet fully elucidated. This study aims to detect the possible function of NDRG1 in gastric cancer progression. In this study, 112 paired gastric cancer tissues and corresponding nonmalignant gastric tissues were utilized to identify the differential protein expression of NDRG1 by immunohistochemistry and its clinical significance was analyzed. Furthermore, 49 of 112 paired gastric specimens were used to detect the differential mRNA expression by real-time PCR. The over expression of NDRG1 in human gastric cancer cell line AGS by PcDNA3.1-NDRG1 transfection was utilized to detect the role of NDRG1 in regulating the biological behavior of gastric cancer. NDRG1 expression was significantly decreased in primary gastric cancer tissues, compared with its corresponding nonmalignant gastric tissues (p < 0.05), and its decreased expression was significantly associated with lymph node metastasis (p < 0.01), invasion depth (p < 0.01) and differentiation (p < 0.05). Additionally, the overall survival rate of gastric cancer patients with high expression of NDRG1 was higher than those with low expression during the follow-up period. NDRG1 overexpression suppressed cells proliferation, invasion and induced a G1 cell cycle arrest in gastric cancer. Furthermore, the down-regulation of NDRG1 in gastric cancer metastatic progression was correlated to E-cadherin and MMP-9. Our results verify that NDRG1 acts as a tumor suppressor gene and may play an important role in the metastasis progression and prognosis of gastric cancer.

  5. Activation of nuclear PTEN by inhibition of Notch signaling induces G2/M cell cycle arrest in gastric cancer.

    PubMed

    Kim, S-J; Lee, H-W; Baek, J-H; Cho, Y-H; Kang, H G; Jeong, J S; Song, J; Park, H-S; Chun, K-H

    2016-01-14

    Mutation in PTEN has not yet been detected, but its function as a tumor suppressor is inactivated in many cancers. In this study we determined that, activated Notch signaling disables PTEN by phosphorylation and thereby contributes to gastric tumorigenesis. Notch inhibition by small interfering RNA or γ-secretase inhibitor (GSI) induced mitotic arrest and apoptosis in gastric cancer cells. Notch inhibition induced dephosphorylation in the C-terminal domain of PTEN, which led to PTEN nuclear localization. Overexpression of activated Notch1-induced phosphorylation of PTEN and reversed GSI-induced mitotic arrest. Dephosphorylated nuclear PTEN caused prometaphase arrest by interaction with the cyclin B1-CDK1 complex, resulting in their accumulation in the nucleus and subsequent apoptosis. We found a correlation between high expression levels of Notch1 and low survival rates and, similarly, between reduced nuclear PTEN expression and increasing the TNM classification of malignant tumours stages in malignant tissues from gastric cancer patients. The growth of Notch1-depleted gastric tumors was significantly retarded in xenografted mice, and in addition, PTEN deletion restored growth similar to control tumors. We also demonstrated that combination treatment with GSI and chemotherapeutic agents significantly reduced the orthotopically transplanted gastric tumors in mice without noticeable toxicity. Overall, our findings suggest that inhibition of Notch signaling can be employed as a PTEN activator, making it a potential target for gastric cancer therapy.

  6. Leptin activates STAT and ERK2 pathways and induces gastric cancer cell proliferation

    SciTech Connect

    Pai, Rama . E-mail: rpai@uci.edu; Lin Cal; Tran, Teresa; Tarnawski, Andrzej . E-mail: atarnawski@yahoo.com

    2005-06-17

    Although leptin is known to induce proliferative response in gastric cancer cells, the mechanism(s) underlying this action remains poorly understood. Here, we provide evidence that leptin-induced gastric cancer cell proliferation involves activation of STAT and ERK2 signaling pathways. Leptin-induced STAT3 phosphorylation is independent of ERK2 activation. Leptin increases SHP2 phosphorylation and enhances binding of Grb2 to SHP2. Inhibition of SHP2 expression with siRNA but not SHP2 phosphatase activity abolished leptin-induced ERK2 activation. While JAK inhibition with AG490 significantly reduced leptin-induced ERK2, STAT3 phosphorylation, and cell proliferation, SHP2 inhibition only partially reduced cancer cell proliferation. Immunostaining of gastric cancer tissues displayed local overexpression of leptin and its receptor indicating that leptin might be produced and act locally in a paracrine or autocrine manner. These findings indicate that leptin promotes cancer growth by activating multiple signaling pathways and therefore blocking its action at the receptor level could be a rational therapeutic strategy.

  7. Angiogenesis inhibitors in gastric and gastroesophageal junction cancer.

    PubMed

    Roviello, Giandomenico; Petrioli, Roberto; Marano, Luigi; Polom, Karol; Marrelli, Daniele; Perrella, Armando; Roviello, Franco

    2016-01-01

    Despite significant improvements in systemic chemotherapy during the past two decades, the prognosis of patients with advanced gastric and gastroesophageal junction adenocarcinoma remains poor. Because of molecular heterogeneity, it is essential to classify tumors based on the underlying oncogenic pathways and to develop targeted therapies acting on individual tumors. Unfortunately, although a number of molecular targets have been studied, very few of these agents can be used in a clinical setting. In this review, we summarize the available data on anti-angiogenic agents in advanced/metastatic gastric cancer. PMID:26329368

  8. Reduced mRNA expression levels of MBD2 and MBD3 in gastric carcinogenesis.

    PubMed

    Pontes, Thaís Brilhante; Chen, Elizabeth Suchi; Gigek, Carolina Oliveira; Calcagno, Danielle Queiroz; Wisnieski, Fernanda; Leal, Mariana Ferreira; Demachki, Samia; Assumpção, Paulo Pimentel; Artigiani, Ricardo; Lourenço, Laércio Gomes; Burbano, Rommel Rodriguez; Arruda Cardoso Smith, Marília

    2014-04-01

    Aberrant methylation has been reported in several neoplasias, including gastric cancer. The methyl-CpG-binding domain (MBD) family proteins have been implicated in the chromatin remodeling process, leading to the modulation of gene expression. To evaluate the role of MBD2 and MBD3 in gastric carcinogenesis and the possible association with clinicopathological characteristics, we assessed the mRNA levels and promoter methylation patterns in gastric tissues. In this study, MBD2 and MBD3 mRNA levels were determined by RT-qPCR in 28 neoplastic and adjacent nonneoplastic and 27 gastritis and non-gastritis samples. The promoter methylation status was determined by bisulfite sequencing, and we found reduced MBD2 and MBD3 levels in the neoplastic samples compared with the other groups. Moreover, a strong correlation between the MBD2 and MBD3 expression levels was observed in each set of paired samples. Our data also showed that the neoplastic tissues exhibited higher MBD2 promoter methylation than the other groups. Interestingly, the non-gastritis group was the only one with positive methylation in the MBD3 promoter region. Furthermore, a weak correlation between gene expression and methylation was observed. Therefore, our data suggest that DNA methylation plays a minor role in the regulation of MBD2 and MBD3 expression, and the presence of methylation at CpGs that interact with transcription factor complexes might also be involved in the modulation of these genes. Moreover, reduced mRNA expression of MBD2 and MBD3 is implicated in gastric carcinogenesis, and thus, further investigations about these genes should be conducted for a better understanding of the role of abnormal methylation involved in this neoplasia. PMID:24338710

  9. Bleeding gastric cancer in young and elderly patients

    PubMed Central

    Pucheanu, X; Beuran, M

    2015-01-01

    Purpose: This study tried to find the differences between gastric cancer in young and elderly, in addition through the importance of the presence of the upper gastrointestinal bleeding, with two examples of clinical cases. Methods: Two groups of patients divided by age were compared. The first group consisted of 13 cases of patients aged between 32 and 41, and the second consisted of 15 cases, aged 80 to 87 years. The variables considered were: sex, personal history and family history, onset-admission interval, number of days of hospitalization after surgery, the number of days until discharge, personal history/ family history, tumor location, admission diagnosis, intervention type, value hemoglobin on admission, the way externalizing hemorrhage appeared, stage, tumor type/ degree of differentiation of its kind lymph dissection, postoperative complications and deaths. Results: The interval from symptom onset to hospital admission was higher in young people with a greater weight loss and malignant ulcer history or upload family were smokers, but apparently with a lower complication rate. In the elderly, the anemic syndrome was the main event and the complications were more related to comorbidities. Conclusions: Prolonged gastric distress in young patients, associated with smoking, personal history of ulcer and family history of neoplasia should guide the diagnosis to gastric cancer. Anemic syndrome in the elderly may be due to the gastric cancer, and complications are due to comorbidities. PMID:26351541

  10. MiR-203 inhibits tumor invasion and metastasis in gastric cancer by ATM.

    PubMed

    Zhou, Ping; Jiang, Nan; Zhang, Guo-Xia; Sun, Qing

    2016-08-01

    Gastric cancer is one of the most common malignancies in the world. A number of miRNAs are aberrantly expressed during the progression of gastric cancer. In this study, we aimed to investigate the role of miR-203 in the invasion and metastasis of gastric cancer and the potential mechanism of the effect of miR-203 on the tumor progression of gastric cancer. Our results showed that miR-203 was significantly downregulated in gastric cancer tissues and cells, while ataxia telangiectasia mutated kinase (ATM) was upregulated in gastric cancer tissues and cells and was directly regulated by miR-203. Ectopic overexpression of miR-203 inhibited the colony formation, migration, and invasion of gastric cancer cells. In addition, miR-203 overexpression significantly suppressed the protein level of Snail and obviously promoted the protein level of E-cadherin in gastric cancer cells. ATM knockdown phenocopied the effect of miR-203 overexpression. These results suggested that miR-203 suppressed the migration and invasion of gastric cancer through regulating the level of ATM-mediated-Snail and E-cadherin. MiR-203 might be a novel therapeutic strategy for the treatment of gastric cancer. PMID:27542403

  11. MiR-203 inhibits tumor invasion and metastasis in gastric cancer by ATM.

    PubMed

    Zhou, Ping; Jiang, Nan; Zhang, Guo-Xia; Sun, Qing

    2016-08-01

    Gastric cancer is one of the most common malignancies in the world. A number of miRNAs are aberrantly expressed during the progression of gastric cancer. In this study, we aimed to investigate the role of miR-203 in the invasion and metastasis of gastric cancer and the potential mechanism of the effect of miR-203 on the tumor progression of gastric cancer. Our results showed that miR-203 was significantly downregulated in gastric cancer tissues and cells, while ataxia telangiectasia mutated kinase (ATM) was upregulated in gastric cancer tissues and cells and was directly regulated by miR-203. Ectopic overexpression of miR-203 inhibited the colony formation, migration, and invasion of gastric cancer cells. In addition, miR-203 overexpression significantly suppressed the protein level of Snail and obviously promoted the protein level of E-cadherin in gastric cancer cells. ATM knockdown phenocopied the effect of miR-203 overexpression. These results suggested that miR-203 suppressed the migration and invasion of gastric cancer through regulating the level of ATM-mediated-Snail and E-cadherin. MiR-203 might be a novel therapeutic strategy for the treatment of gastric cancer.

  12. Up-regulation of neogenin-1 increases cell proliferation and motility in gastric cancer

    PubMed Central

    Kim, Seok-Jun; Wang, Yuan-Guo; Lee, Hyun-Woo; Gu Kang, Hyeok; La, Sun-Hyuk; Ju Choi, Il; Irimura, Tatsuro; Ro, Jae Y.; Bresalier, Robert S.; Chun, Kyung-Hee

    2014-01-01

    Although elevated expression of neogenin-1 has been detected in human gastric cancer tissue, its role in gastric tumorigenesis remains unclear due to the lack of neogenin-1 studies in cancer. Therefore, we demonstrated here the function and regulatory mechanism of neogenin-1 in gastric cancer. Neogenin-1 ablation decreased proliferation and migration of gastric cancer cells, whereas its over-expression reversed these effects. Xenografted analyses using gastric cancer cells displayed statistically significant inhibition of tumor growth by neogenin-1 depletion. Interestingly, galectin-3 interacted with HSF-1 directly, which facilitated nuclear-localization and binding on neogenin-1 promoter to drive its transcription and gastric cancer cell motility. The galectin-3-increased gastric cancer cell motility was down-regulated by HSF-1 depletion. Moreover, the parallel expression patterns of galectin-3 and neogenin-1, as well as those of HSF-1 and neogenin-1, were detected in the malignant tissues of gastric cancer patients. Taken together, high-expression of neogenin-1 promotes gastric cancer proliferation and motility and its expression is regulated by HSF-1 and galectin-3 interaction. In addition, we propose further studies for neogenin-1 and its associated pathways to provide them as a proper target for gastric cancer therapy. PMID:24930499

  13. Helicobacter pylori-negative gastric cancer: characteristics and endoscopic findings.

    PubMed

    Yamamoto, Yorimasa; Fujisaki, Junko; Omae, Masami; Hirasawa, Toshiaki; Igarashi, Masahiro

    2015-07-01

    Helicobacter pylori (H. pylori) leads to chronic gastritis and eventually causes gastric cancer. The prevalence of H. pylori infection is gradually decreasing with improvement of living conditions and eradication therapy. However, some reports have described cases of H. pylori-negative gastric cancers (HpNGC), and the prevalence was 0.42-5.4% of all gastric cancers. Diagnostic criteria of HpNGC vary among the different reports; thus, they have not yet been definitively established. We recommend negative findings in two or more methods that include endoscopic or pathological findings or serum pepsinogen test, and negative urease breath test or serum immunoglobulin G test and no eradication history the minimum criteria for diagnosis of HpNGC. The etiology of gastric cancers, excluding H. pylori infection, is known to be associated with several factors including lifestyle, viral infection, autoimmune disorder and germline mutations, but the main causal factor of HpNGC is still unclear. Regarding the characteristics of HpNGC, the undifferentiated type (UD-type) is more frequent than the differentiated type (D-type). The UD-type is mainly signet ring-cell carcinoma that presents as a discolored lesion in the lower or middle part of the stomach in relatively young patients. The gross type is flat or depressed. The D-type is mainly gastric adenocarcinoma of the fundic gland type that presents as a submucosal tumor-like or flat or depressed lesion in the middle and upper part of the stomach in relatively older patients. Early detection of HpNGC enables minimally invasive treatment which preserves the patient's quality of life. Endoscopists should fully understand the characteristics and endoscopic findings of HpNGC.

  14. Small bowel diverticulosis in patient with early gastric cancer

    PubMed Central

    Kim, Pyeong Su; Jung, Eun-Joo

    2014-01-01

    Jejunal and ileal diverticula are rare in adults. Duodenal diverticula are five times more prevalent than jejunoileal diverticula. Most patients are asymptomatic. However, chronic symptoms including intermittent abdominal pain, flatulence, diarrhea and constipation are seen in 10%-30% of patients. Gastric cancer is the second most common cancer in South Korea and here we report a case of early gastric cancer with multiple duodenal and jejunal diverticula. A 67-year-old woman was admitted to Konkuk University Medical Center with chronic diarrhea and weight loss of 19 kg over 2 months. Following gastroduodenoscopy, we identified adenocarcinoma of the lower body of the stomach. On abdominopelvic computed tomography, diverticula of duodenum and jejunum were found. Patient underwent distal gastrectomy and gastroduodenostomy with lymphadenectomy. She was discharged on the tenth postoperative day without complications. PMID:25317417

  15. Prognostic value of CAPZA1 overexpression in gastric cancer

    PubMed Central

    LEE, YOUNG-JOON; JEONG, SANG-HO; HONG, SOON-CHAN; CHO, BOK-IM; HA, WOO-SONG; PARK, SOON-TAE; CHOI, SANG-KYUNG; JUNG, EUN-JUNG; JU, YOUNG-TAE; JEONG, CHI-YOUNG; KIM, JAE WON; LEE, CHANG WON; YOO, JIYUN; KO, GYUNG HYUCK

    2013-01-01

    F-actin capping protein α1 subunit (CAPZA1) was previously identified in a proteomic analysis of human gastric cancer clinical specimens and selected for further study. The association between CAPZA1 overexpression, detected by immunohistochemistry, and clinicopathological features including survival were evaluated. In vitro gain-of-function and loss-of-function approaches were utilized to assess the function of CPAZA1 in malignancy. Univariate analysis revealed that poorly differentiated disease, according to the World Health Organization (WHO) classification, advanced T stage, positive lymph nodes, high TNM stage, D2 lymph node dissection, adjuvant chemotherapy and CAPZA1 underexpression were significantly associated with cancer-related death (p<0.05); however, only high TNM stage remained significantly associated by multivariate analysis (p<0.01). CAPZA1 overexpression was associated with well differentiated histology, smaller tumor size, lower T stage, absence of lymph node metastasis, lower TNM stage, lower recurrence rate and longer survival time, compared to CAPZA1 underexpression. In vitro, forced expression of CAPZA1 caused a significant decrease in gastric cancer cell migration and invasion, whereas CAPZA1 depletion had the opposite effect. The present study suggests that CAPZA1 could be a marker of good prognosis in gastric cancer and shows that CAPZA1 is associated with decreased cancer cell migration and invasion. PMID:23545944

  16. Adenocarcinoma of the GEJ: gastric or oesophageal cancer?

    PubMed

    Rüschoff, J

    2012-01-01

    According to WHO (2010) adenocarcinomas of the esophagogastric junction (GEJ) are defined as tumors that cross the most proximal extent of the gastric folds regardless of where the bulk of the tumor lies. In addition, these neoplasms are now classified as esophageal cancers by UICC (2010). Recent studies, however, revealed two types of carcinogenesis in the distal oesophagus and at the GEJ, one of intestinal type (about 80 %) and the other of gastric type (about 20 %). These are characterized by marked differences in morphology, tumor stage at diagnosis, and prognosis. Furthermore, both cancer types show different targetable biomarker expression profiles such as Her2 in the intestinal and EGFR in the non-intestinal pathway indicating new therapy options. Due to the fact that carcinomas of the intestinal pathway were typically associated with Barrett's mucosa which was not the case in the non-intestinal-type tumors, this challenges the paradigm "no goblets no Barrett's". Moreover, even the cancer risk of intestinal-type metaplasia has seriously been questioned by a Danish population-based study where Barrett's mucosa turned out to be only a weak indicator of esophageal and GEJ cancer (1 case in 860 patients years). Thus, two biologically different types of cancer arise at the GEJ-esophageal and gastric type that open distinctive targeted treatment options and also question our current concept about the diagnostics of potential precursor lesions as well as the associated screening and surveillance strategy.

  17. Oxyntic atrophy, metaplasia and gastric cancer

    PubMed Central

    Goldenring, James R.; Nam, Ki Taek

    2015-01-01

    The process of gastric carcinogenesis involves the loss of parietal cells (oxyntic atrophy) and subsequent replacement of the normal gastric lineages with metaplastic lineages. In humans, two metaplastic lineages develop as sequelae of chronic Helicobacter pylori infection: intestinal metaplasia and Spasmolytic Polypeptide-expressing Metaplasia (SPEM). Mouse models of both chronic Helicobacter infection and acute pharmacological oxyntic atrophy have led to the recognition that SPEM arises from transdifferentiation of mature chief cells. The presence of inflammation promotes the expansion of SPEM in mice. Furthermore, studies in Mongolian gerbils as well as increasing evidence from human studies indicates that SPEM likely represents a precursor for development of intestinal metaplasia. These findings indicate that loss of parietal cells, augmented by chronic inflammation, leads to a cascade of metaplastic events. Identification of specific biomarkers for SPEM and intestinal metaplasia hold promise for providing both early detection of pre-neoplasia as well as information on prognostic outcome following curative resection. PMID:21075342

  18. Nutrition in Patients with Gastric Cancer: An Update

    PubMed Central

    Rosania, Rosa; Chiapponi, Costanza; Malfertheiner, Peter; Venerito, Marino

    2016-01-01

    Background Nutritional management of patients with gastric cancer (GC) represents a challenge. Summary This review provides an overview of the present evidence on nutritional support in patients with GC undergoing surgery as well as in those with advanced disease Key Message For patients undergoing surgery, the preoperative nutritional condition directly affects postoperative prognosis, overall survival and disease-specific survival. Perioperative nutritional support enriched with immune-stimulating nutrients reduces overall complications and hospital stay but not mortality after major elective gastrointestinal surgery. Early enteral nutrition after surgery improves early and long-term postoperative nutritional status and reduces the length of hospitalization as well. Vitamin B12 and iron deficiency are common metabolic sequelae after gastrectomy and warrant appropriate replacement. In malnourished patients with advanced GC, short-term home complementary parenteral nutrition improves the quality of life, nutritional status and functional status. Total home parenteral nutrition represents the only modality of caloric intake for patients with advanced GC who are unable to take oral or enteral nutrition Practical Implications Early evaluations of nutritional status and nutritional support represent key aspects in the management of GC patients with both operable and advanced disease. PMID:27403412

  19. Current role of minimally invasive approaches in the treatment of early gastric cancer

    PubMed Central

    El-Sedfy, Abraham; Brar, Savtaj S; Coburn, Natalie G

    2014-01-01

    Despite declining incidence, gastric cancer remains one of the most common cancers worldwide. Early detection in population-based screening programs has increased the number of cases of early gastric cancer, representing approximately 50% of newly detected gastric cancer cases in Asian countries. Endoscopic mucosal resection and endoscopic submucosal dissection have become the preferred therapeutic techniques in Japan and Korea for the treatment of early gastric cancer patients with a very low risk of lymph node metastasis. Laparoscopic and robotic resections for early gastric cancer, including function-preserving resections, have propagated through advances in technology and surgeon experience. The aim of this paper is to discuss the recent advances in minimally invasive approaches in the treatment of early gastric cancer. PMID:24833843

  20. Function-preserving gastrectomy for early gastric cancer.

    PubMed

    Hiki, Naoki; Nunobe, Souya; Kubota, Takeshi; Jiang, Xiaohua

    2013-08-01

    The number of early gastric cancer (EGC) cases has been increasing because of improved diagnostic procedures. Applications of function-preserving gastric cancer surgery may therefore also be increasing because of its low incidence of lymph node metastasis, excellent survival rates, and the possibility of less-invasive procedures such as laparoscopic gastrectomy being used in combination. Pylorus-preserving gastrectomy (PPG) with radical lymph node dissection is one such function-preserving procedure that has been applied for EGC, with the indications, limitations, and survival benefits of PPG already reported in several retrospective studies. Laparoscopy-assisted proximal gastrectomy has also been applied for EGC of the upper third of the stomach, although this procedure can be associated with the 2 major problems of reflux esophagitis and carcinoma arising in the gastric stump. In the patient with EGC in the upper third of the stomach, laparoscopy-assisted subtotal gastrectomy with a preserved very small stomach may provide a better quality of life for the patients and fewer postoperative complications. Finally, the laparoscopy endoscopy cooperative surgery procedure combines endoscopic submucosal dissection with laparoscopic gastric wall resection, which prevents excessive resection and deformation of the stomach after surgery and was recently applied for EGC cases without possibility of lymph node metastasis. Function-preserving laparoscopic gastrectomy is recommended for the treatment of EGC if the indication followed by accurate diagnosis is strictly confirmed. Preservation of remnant stomach sometimes causes severe postoperative dysfunctions such as delayed gastric retention in PPG, esophageal reflux in PG, and gastric stump carcinoma in the remnant stomach. Moreover, these techniques present technical difficulties to the surgeon. Although many retrospective studies showed the functional benefit or oncological safety of function-preserving gastrectomy

  1. [Radiotherapy in cancers of the oesophagus, the gastric cardia and the stomach].

    PubMed

    Créhange, G; Huguet, F; Quero, L; N'Guyen, T V; Mirabel, X; Lacornerie, T

    2016-09-01

    Localized oesophageal and gastric cancers have a poor prognosis. In oesophageal cancer, external radiotherapy combined with concomitant chemotherapy is accepted as part of the therapeutic armamentarium in a curative intent in the preoperative setting for resectable tumours; or without surgery in inoperable patients or non-resectable tumours due to wide local and/or regional extension. Data from the literature show conflicting results with no clinical evidence in favour of either a unique dose protocol or consensual target volume definition in the setting of exclusive chemoradiation. In the preoperative setting, chemoradiotherapy has become the standard in oesophageal cancer, even though there is no evidence that surgery may be beneficial in locally advanced tumours that respond to radiotherapy and chemotherapy. The main cause of failure after exclusive chemoradiotherapy in oesophageal cancer is locoregional relapse suggesting that doses and volumes usually considered may be inadequate. In gastric cancer, radiotherapy may be indicated postoperatively in patients with resected tumours that include less than D2 lymph node dissection or in the absence of perioperative chemotherapy. Preoperative chemoradiotherapy in gastric cancers is still under investigation. The evolving techniques of external radiotherapy, such as image-guided radiotherapy (IMRT) and volumetric modulated arctherapy (VMAT) have reduced the volume of lung and heart exposed to radiation, which seems to have diminished radiotherapy-related morbi-mortality rates. Given this, quality assurance for radiotherapy and protocols for radiotherapy delivery must be better standardized. This article on the indications for radiotherapy and the techniques used in oesophageal and gastric cancers is included in a special issue dedicated to national recommendations from the French society of radiation oncology (SFRO) on radiotherapy indications, planning, dose prescription, and techniques of radiotherapy delivery. PMID

  2. [Radiotherapy in cancers of the oesophagus, the gastric cardia and the stomach].

    PubMed

    Créhange, G; Huguet, F; Quero, L; N'Guyen, T V; Mirabel, X; Lacornerie, T

    2016-09-01

    Localized oesophageal and gastric cancers have a poor prognosis. In oesophageal cancer, external radiotherapy combined with concomitant chemotherapy is accepted as part of the therapeutic armamentarium in a curative intent in the preoperative setting for resectable tumours; or without surgery in inoperable patients or non-resectable tumours due to wide local and/or regional extension. Data from the literature show conflicting results with no clinical evidence in favour of either a unique dose protocol or consensual target volume definition in the setting of exclusive chemoradiation. In the preoperative setting, chemoradiotherapy has become the standard in oesophageal cancer, even though there is no evidence that surgery may be beneficial in locally advanced tumours that respond to radiotherapy and chemotherapy. The main cause of failure after exclusive chemoradiotherapy in oesophageal cancer is locoregional relapse suggesting that doses and volumes usually considered may be inadequate. In gastric cancer, radiotherapy may be indicated postoperatively in patients with resected tumours that include less than D2 lymph node dissection or in the absence of perioperative chemotherapy. Preoperative chemoradiotherapy in gastric cancers is still under investigation. The evolving techniques of external radiotherapy, such as image-guided radiotherapy (IMRT) and volumetric modulated arctherapy (VMAT) have reduced the volume of lung and heart exposed to radiation, which seems to have diminished radiotherapy-related morbi-mortality rates. Given this, quality assurance for radiotherapy and protocols for radiotherapy delivery must be better standardized. This article on the indications for radiotherapy and the techniques used in oesophageal and gastric cancers is included in a special issue dedicated to national recommendations from the French society of radiation oncology (SFRO) on radiotherapy indications, planning, dose prescription, and techniques of radiotherapy delivery.

  3. A mutational signature in gastric cancer suggests therapeutic strategies

    PubMed Central

    Alexandrov, Ludmil B.; Nik-Zainal, Serena; Siu, Hoi Cheong; Leung, Suet Yi; Stratton, Michael R

    2015-01-01

    Targeting defects in the DNA repair machinery of neoplastic cells, for example, those due to inactivating BRCA1 and/or BRCA2 mutations, has been used for developing new therapies in certain types of breast, ovarian and pancreatic cancers. Recently, a mutational signature was associated with failure of double-strand DNA break repair by homologous recombination based on its high mutational burden in samples harbouring BRCA1 or BRCA2 mutations. In pancreatic cancer, all responders to platinum therapy exhibit this mutational signature including a sample that lacked any defects in BRCA1 or BRCA2. Here, we examine 10,250 cancer genomes across 36 types of cancer and demonstrate that, in addition to breast, ovarian and pancreatic cancers, gastric cancer is another cancer type that exhibits this mutational signature. Our results suggest that 7–12% of gastric cancers have defective double-strand DNA break repair by homologous recombination and may benefit from either platinum therapy or PARP inhibitors. PMID:26511885

  4. A mutational signature in gastric cancer suggests therapeutic strategies

    DOE PAGESBeta

    Alexandrov, Ludmil B.; Nik-Zainal, Serena; Siu, Hoi Cheong; Leung, Suet Yi; Stratton, Michael R.

    2015-10-29

    Targeting defects in the DNA repair machinery of neoplastic cells, for example, those due to inactivating BRCA1 and/or BRCA2 mutations, has been used for developing new therapies in certain types of breast, ovarian and pancreatic cancers. Recently, a mutational signature was associated with failure of double-strand DNA break repair by homologous recombination based on its high mutational burden in samples harbouring BRCA1 or BRCA2 mutations. In pancreatic cancer, all responders to platinum therapy exhibit this mutational signature including a sample that lacked any defects in BRCA1 or BRCA2. Here, we examine 10,250 cancer genomes across 36 types of cancer andmore » demonstrate that, in addition to breast, ovarian and pancreatic cancers, gastric cancer is another cancer type that exhibits this mutational signature. Furthermore, our results suggest that 7–12% of gastric cancers have defective double-strand DNA break repair by homologous recombination and may benefit from either platinum therapy or PARP inhibitors.« less

  5. A mutational signature in gastric cancer suggests therapeutic strategies

    SciTech Connect

    Alexandrov, Ludmil B.; Nik-Zainal, Serena; Siu, Hoi Cheong; Leung, Suet Yi; Stratton, Michael R.

    2015-10-29

    Targeting defects in the DNA repair machinery of neoplastic cells, for example, those due to inactivating BRCA1 and/or BRCA2 mutations, has been used for developing new therapies in certain types of breast, ovarian and pancreatic cancers. Recently, a mutational signature was associated with failure of double-strand DNA break repair by homologous recombination based on its high mutational burden in samples harbouring BRCA1 or BRCA2 mutations. In pancreatic cancer, all responders to platinum therapy exhibit this mutational signature including a sample that lacked any defects in BRCA1 or BRCA2. Here, we examine 10,250 cancer genomes across 36 types of cancer and demonstrate that, in addition to breast, ovarian and pancreatic cancers, gastric cancer is another cancer type that exhibits this mutational signature. Furthermore, our results suggest that 7–12% of gastric cancers have defective double-strand DNA break repair by homologous recombination and may benefit from either platinum therapy or PARP inhibitors.

  6. History, Pathogenesis, and Management of Familial Gastric Cancer: Original Study of John XXIII's Family

    PubMed Central

    Corso, Giovanni; Roncalli, Fabrizio; Marrelli, Daniele; Carneiro, Fátima; Roviello, Franco

    2013-01-01

    Background. Hereditary diffuse gastric cancer is associated with the E-cadherin germline mutations, but genetic determinants have not been identified for familial intestinal gastric carcinoma. The guidelines for hereditary diffuse gastric cancer are clearly established; however, there are no defined recommendations for the management of familial intestinal gastric carcinoma. Methods. In this study we describe Pope John XXIII's pedigree that harboured gastric cancer as well as six other family members. Family history was analysed according to the International Gastric Cancer Linkage Consortium criteria, and gastric tumours were classified in accord with the last Japanese guidelines. Results. Seven out of 109 members in this pedigree harboured gastric cancer, affecting two consecutive generations. John XXIII's clinical tumour (cTN) was classified as cT4bN3a (IV stage). In two other cases, gastric carcinomas were classified as intestinal histotype and staged as pT1bN0 and pT2N2, respectively. Conclusions. Pope John XXIII's family presents a strong aggregation for gastric cancer affecting almost seven members; it spreads through two consecutive generations. In absence of defined genetic causes and considering the increased risk of gastric cancer's development in these families, as well as the high mortality rates and advanced stages, we propose an intensive surveillance protocol for asymptomatic members. PMID:23484115

  7. Pattern-recognition receptors and gastric cancer.

    PubMed

    Castaño-Rodríguez, Natalia; Kaakoush, Nadeem O; Mitchell, Hazel M

    2014-01-01

    Chronic inflammation has been associated with an increased risk of several human malignancies, a classic example being gastric adenocarcinoma (GC). Development of GC is known to result from infection of the gastric mucosa by Helicobacter pylori, which initially induces acute inflammation and, in a subset of patients, progresses over time to chronic inflammation, gastric atrophy, intestinal metaplasia, dysplasia, and finally intestinal-type GC. Germ-line encoded receptors known as pattern-recognition receptors (PRRs) are critical for generating mature pro-inflammatory cytokines that are crucial for both Th1 and Th2 responses. Given that H. pylori is initially targeted by PRRs, it is conceivable that dysfunction within genes of this arm of the immune system could modulate the host response against H. pylori infection, and subsequently influence the emergence of GC. Current evidence suggests that Toll-like receptors (TLRs) (TLR2, TLR3, TLR4, TLR5, and TLR9), nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) (NOD1, NOD2, and NLRP3), a C-type lectin receptor (DC-SIGN), and retinoic acid-inducible gene (RIG)-I-like receptors (RIG-I and MDA-5), are involved in both the recognition of H. pylori and gastric carcinogenesis. In addition, polymorphisms in genes involved in the TLR (TLR1, TLR2, TLR4, TLR5, TLR9, and CD14) and NLR (NOD1, NOD2, NLRP3, NLRP12, NLRX1, CASP1, ASC, and CARD8) signaling pathways have been shown to modulate the risk of H. pylori infection, gastric precancerous lesions, and/or GC. Further, the modulation of PRRs has been suggested to suppress H. pylori-induced inflammation and enhance GC cell apoptosis, highlighting their potential relevance in GC therapeutics. In this review, we present current advances in our understanding of the role of the TLR and NLR signaling pathways in the pathogenesis of GC, address the involvement of other recently identified PRRs in GC, and discuss the potential implications of PRRs in GC immunotherapy.

  8. Pattern-Recognition Receptors and Gastric Cancer

    PubMed Central

    Castaño-Rodríguez, Natalia; Kaakoush, Nadeem O.; Mitchell, Hazel M.

    2014-01-01

    Chronic inflammation has been associated with an increased risk of several human malignancies, a classic example being gastric adenocarcinoma (GC). Development of GC is known to result from infection of the gastric mucosa by Helicobacter pylori, which initially induces acute inflammation and, in a subset of patients, progresses over time to chronic inflammation, gastric atrophy, intestinal metaplasia, dysplasia, and finally intestinal-type GC. Germ-line encoded receptors known as pattern-recognition receptors (PRRs) are critical for generating mature pro-inflammatory cytokines that are crucial for both Th1 and Th2 responses. Given that H. pylori is initially targeted by PRRs, it is conceivable that dysfunction within genes of this arm of the immune system could modulate the host response against H. pylori infection, and subsequently influence the emergence of GC. Current evidence suggests that Toll-like receptors (TLRs) (TLR2, TLR3, TLR4, TLR5, and TLR9), nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) (NOD1, NOD2, and NLRP3), a C-type lectin receptor (DC-SIGN), and retinoic acid-inducible gene (RIG)-I-like receptors (RIG-I and MDA-5), are involved in both the recognition of H. pylori and gastric carcinogenesis. In addition, polymorphisms in genes involved in the TLR (TLR1, TLR2, TLR4, TLR5, TLR9, and CD14) and NLR (NOD1, NOD2, NLRP3, NLRP12, NLRX1, CASP1, ASC, and CARD8) signaling pathways have been shown to modulate the risk of H. pylori infection, gastric precancerous lesions, and/or GC. Further, the modulation of PRRs has been suggested to suppress H. pylori-induced inflammation and enhance GC cell apoptosis, highlighting their potential relevance in GC therapeutics. In this review, we present current advances in our understanding of the role of the TLR and NLR signaling pathways in the pathogenesis of GC, address the involvement of other recently identified PRRs in GC, and discuss the potential implications of PRRs in GC immunotherapy

  9. Entirely Laparoscopic Gastrectomy and Colectomy for Remnant Gastric Cancer with Gastric Outlet Obstruction and Transverse Colon Invasion

    PubMed Central

    Kim, Hyun Il

    2015-01-01

    It is well known that gastrectomy with curative intent is the best way to improve outcomes of patients with remnant gastric cancer. Recently,several investigators reported their experiences with laparoscopic gastrectomy of remnant gastric cancer. We report the case of an 83-year-old female patient who was diagnosed with remnant gastric cancer with obstruction. She underwent an entirely laparoscopic distal gastrectomy with colectomy because of direct invasion of the transverse colon. The operation time was 200 minutes. There were no postoperative complications. The pathologic stage was T4b (transverse colon) N0M0. Our experience suggests that laparoscopic surgerycould be an effective method to improve the surgical outcomes of remnant gastric cancer patients. PMID:26819808

  10. The Role of Endoscopic Ultrasonography in T Staging: Early Gastric Cancer and Esophageal Cancer

    PubMed Central

    2013-01-01

    While a number of diagnostic methods have been developed, endoscopic ultrasound (EUS) still takes the most important role in the preoperative evaluation of esophageal cancer. EUS can detect lesions of all esophageal cancer and can accurately perform T staging. In a recent meta-analysis of EUS in esophageal cancer, the sensitivity and specificity of EUS on esophageal cancer were 81.6% and 99.4% in T1, 81.4% and 96.3% in T2, 91.4% and 94.4% in T3, and 92.4% and 97.4% in T4, respectively. The use of EUS can reduce unnecessary surgeries and lead to apply proper treatments to patients. The advance of endoscopic submucosal dissection have necessitated the presurgical detection of early cancer lesions without lymph node metastasis. Understanding the practical meanings of images shown by EUS is important to decide patients for whom endoscopic treatments can be effective. In early gastric cancer, EUS can accurately predict mucosal and SM1 (invasion into the submucosal layer of less than 500 µm from muscularis mucosa) lesions, which are considered as good indications for endoscopic treatments. PMID:23767033

  11. Relationship Between Interleukin-10 Gene C-819T Polymorphism and Gastric Cancer Risk: Insights From a Meta-Analysis.

    PubMed

    Cui, Xigang; Huang, Qingxian; Li, Xianglin; Liu, Fang; Wang, Dan; Yan, Dong; Wang, Bin; Yang, Chunhua; Mi, Jia; Tian, Geng

    2016-01-01

    BACKGROUND As a pleiotropic cytokine, interleukin-10 (IL-10) plays a regulatory role in carcinogenesis and tumor growth. The aim of this meta-analysis was to assess the susceptibility of the IL-10 gene C-819T polymorphism to gastric cancer. MATERIAL AND METHODS Study identification and data extraction were independently completed by 2 authors. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated and summarized. RESULTS In total, 11 articles including 1960 gastric cancer patients and 3705 controls were qualified. Overall analyses revealed a 13% reduced risk of gastric cancer conferred by the -819T allele relative to the -819C allele (OR=0.87; 95% CI: 0.77-0.97; P=0.016), without heterogeneity (I2=35.1%). In subgroup analyses, a significant difference was identified in East Asian populations (OR=0.85; 95% CI: 0.73-0.98; P=0.029, I2=43.6%), for gastric adenocarcinoma (OR=0.80; 95% CI: 0.66-0.96; P=0.017, I2=0.0%), and in population-based studies (OR=0.81; 95% CI: 0.70-0.93; P=0.003, I2=0.0%). The visual funnel plots and Egger's tests suggested no evidence of publication bias. CONCLUSIONS Extending previous findings, we demonstrate a protective role of the IL-10 gene -819T allele in susceptibility to gastric cancer, and this role was more evident for gastric adenocarcinoma. PMID:27516059

  12. [Anti-gastric cancer effect of melatonin and Bcl-2, Bax, p21 and p53 expression changes].

    PubMed

    Xu, Li; Jin, Qing-Dong; Gong, Xi; Liu, Hui; Zhou, Rui-Xiang

    2014-12-25

    In order to investigate the role of melatonin in inhibiting the proliferation of murine gastric cancer and the underlying molecular mechanism, we performed an in vivo study by inoculating murine foregastric carcinoma (MFC) cells in mice, and then tumor-bearing mice were treated with different concentrations of melatonin (i.p.). The changes of Bcl-2, Bax, p21 and p53 expressions in tumor tissue were detected by using real-time fluorescence quantitative RT-PCR and Western blot. We found that: (1) melatonin resulted in reductions of tumor's volume and weight in the gastric cancer-bearing mice and thus showed anti-cancer effect; (2) melatonin reduced Bcl-2 expression, but increased the expression of Bax, p53 and p21 in tumor tissue. Our results suggest that melatonin could inhibit the growth of tumors in gastric cancer-bearing mice through accelerating the apoptosis of tumor cells. PMID:25516522

  13. Citrus Reticulata blanco induces apoptosis in human gastric cancer cells SNU-668.

    PubMed

    Kim, Mi-Ja; Park, Hae Jeong; Hong, Mee Suk; Park, Hi-Joon; Kim, Min-Su; Leem, Kang-Hyun; Kim, Jeung-Beum; Kim, Youn Jung; Kim, Hye Kyung

    2005-01-01

    Citrus fruits have been known to reduce the proliferation of many cancer cells. The antiproliferative effects of Citrus reticulata Blanco (CR) extract, the immature tangerine peel, on human gastric cancer cell line SNU-668 were evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, 4,6-diamidineo-2-phenylindole staining, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay, reverse transcription-polymerase chain reaction expressions of BCL-2, BAX and CASP-3 genes, caspase-3 activity, and immunocytochemistry of caspase-3. From the results of the morphological and biochemical assays, CR (50 microg/ml) increased the apoptosis of human gastric cancer cells with typical apoptotic characteristics, including morphological changes of chromatin condensation and apoptotic body formation. CR (50 microg/ml) reduced the expression of BCL-2, whereas the expression of BAX and CASP-3 was increased compared with the control group. Furthermore, caspase-3 activity and caspase-3 protein expression in the CR-treated group was significantly increased compared with that in control group. These results suggest that CR may induce the apoptosis through the caspase-3 pathway in human gastric cancer cells. PMID:15749633

  14. HOXC6 promotes gastric cancer cell invasion by upregulating the expression of MMP9.

    PubMed

    Chen, Shi-Wei; Zhang, Qing; Xu, Zhi-Feng; Wang, Hai-Ping; Shi, Yi; Xu, Feng; Zhang, Wen-Jian; Wang, Ping; Li, Yong

    2016-10-01

    Previous studies have demonstrated that the homoebox C6 (HOXC6) gene is highly expressed in gastric cancer tissues and is associated with the depth of tumor invasion, and is associated with poor prognosis of gastric cancer patients expressing HOXC6. The present study investigated the effect and underlying mechanism of HOXC6 on the proliferation and metastasis of gastric cancer cells in vitro. Reverse transcription‑quantitative polymerase chain (PCR) reaction was used to investigate the expression levels of HOXC6 in different gastric cancer cell lines and the effect of different levels of expression on the proliferation of gastric cancer cells was determined by cell growth curve and plate colony formation. The effect of HOXC6 on the anchorage‑independent proliferation of gastric cancer cells was determined by soft agar colony formation assay while the Transwell invasion assay was used to investigate the effect of different levels of HOXC6 expression on the invasive and metastatic abilities of gastric cancer cells. Semi‑quantitative PCR was used to detect the effect of different levels of HOXC6 expression on the expression of matrix metalloproteinase (MMP)2 and MMP9 in gastric cancer cells. Immunoblotting was used to assess MMP9 signaling in the gastric cancer cells. The HOXC6 gene is highly expressed in the majority of the gastric cancer cell lines. Overexpression of HOXC6 promoted gastric cancer cell proliferation and colony formation ability while HOXC6 downregulation inhibited cell proliferation and clone forming ability. HOXC6 overexpression also enhanced the soft agar colony formation ability of gastric cancer cells while HOXC6 downregulation decreased the colony formation ability. Upregulated HOXC6 increased the migration and invasion abilities of gastric cancer cells while interfering with HOXC6 expression inhibited the migration and invasion of the gastric cancer cells. The expression of MMP9 was enhanced with an upregulation of HOXC6 expression

  15. Curative gastric resection for the elderly patients suffering from gastric cancer

    PubMed Central

    AL MANSOUR, M.; IZZO, L.; MAZZONE, G.; GABRIELE, R.; DI CELLO, P.; BASSO, L.; RANIERI, E.; COSTI, U.; JOVANOVIC, T.; IZZO, P.

    2016-01-01

    The improvement of the socio-economic conditions and the progress of medicine have extended the life span of the world’s population and as a result, the number of patients with malignant neoplasms has increased. Gastric cancer is the third most common cancer (after lung and prostate) and the second leading cause of death caused by cancer (after lung bronchogenic cell carcinoma) in males; while it’s the fifth cancer by frequency and the fourth cause of cancer death in females. It presents a peculiar geographical distribution with a lower incidence in Western Europe and North America, and higher incidence in the Far East, South America and Eastern Europe. Its incidence in Italy is 122 cases per 100000 inhabitants in males and 83 cases per 100000 inhabitants in females (in Italy). It occurs more frequently in old age, is quite rare in individuals under the age of 45. The aim of this work is to analyze the clinical and pathological characteristics of gastric carcinoma and the feasibility of curative surgery in patients over 75, identifying the factors affecting mortality, morbidity, survival and quality of life after surgery. These data have been compared with those of younger patients to assess the correct type of surgery. PMID:27142820

  16. Bursectomy in gastric cancer surgery: surgical technique and operative safety.

    PubMed

    Blouhos, Konstantinos; Boulas, Konstantinos A; Hatzigeorgiadis, Anestis

    2013-06-01

    Although there is little evidence that bursectomy has clinical benefit, its continuing practice imposes evaluation of bursectomy-related adverse effects, especially pancreatic fistula and intestinal obstruction. The aims of this study were to provide a detailed description of the technique of bursectomy as standardized by the authors and determine if extended surgery for gastric cancer with additional bursectomy can be performed safely in Western population. A total of 72 consecutive patients of median age 76.4 years and mean ASA score grade 2.1, who submitted to D2 or D2+ gastrectomy with additional bursectomy for gastric adenocarcinoma, were prospectively studied. Bursectomy was associated with a median additional operative time of 41 min and a median additional blood loss of 65 ml. The post-operative morbidity rate was 19.4 %. Among various adverse events, pancreatic fistula was observed in three patients (4.2 %) and intestinal obstruction was observed in eight patients (11.1 %) including two cases of delayed gastric emptying, one case of afferent loop syndrome, one case of early postoperative adhesions and four cases of prolonged postoperative ileus. The in-hospital mortality rate was 1.4 %. D2 or D2+ gastrectomy with additional bursectomy can be safely performed in Western patients. Although the incidence of pancreatic fistula that we reported was low, the incidence of bursectomy-related intestinal obstruction was high and should always be kept in mind when performing extended surgery for gastric cancer. PMID:23592040

  17. Endoscopic Submucosal Dissection for Early Gastric Cancers with Uncommon Histology

    PubMed Central

    Kim, Gwang Ha

    2016-01-01

    Endoscopic submucosal dissection (ESD) enables en bloc curative resection of early gastric cancers (EGCs) with a negligible risk of lymph node metastasis (LNM). Although ESD for EGCs with absolute and expanded indications is safe, the results differ between EGCs with specialized and common histologies. EGC with papillary adenocarcinoma is a differentiated-type adenocarcinoma. At present, it is treated with ESD according to the same criteria as other differentiated-type adenocarcinomas. The LNM rate under the current indication criteria is high, and over half of the patients who undergo ESD as a primary treatment for EGC with papillary adenocarcinoma achieve an out-of-ESD result. Gastric carcinoma with lymphoid stroma in EGC has a low LNM rate and a favorable outcome, despite deep submucosal invasion. Patients with this gastric cancer subtype may be good candidates for ESD, even with deep submucosal invasion. Large-scale prospective multi-center studies with longer follow-up periods are needed to set proper ESD criteria for these tumors. Clinicians should be aware of these disease entities and ESD should be more carefully considered for EGCs with papillary adenocarcinoma and gastric carcinoma with lymphoid stroma. PMID:27744663

  18. Alterations of DNA mismatch repair proteins and microsatellite instability levels in gastric cancer cell lines.

    PubMed

    Yao, Yuan; Tao, Hong; Kim, Jae J; Burkhead, Benjamin; Carloni, Emilia; Gasbarrini, Antonio; Sepulveda, Antonia R

    2004-07-01

    Alterations in DNA mismatch repair (MMR) proteins result in microsatellite instability (MSI), increased mutation accumulation at target genes and cancer development. About one-third of gastric cancers display high-level microsatellite instability (MSI-High) and low-level microsatellite instability (MSI-Low) is frequently detected. To determine whether variations in the levels of MMR proteins or mutations in the main DNA MMR genes are associated with MSI-Low and MSI-High in gastric cancer cell lines, the MSI status (MSI-High, MSI-Low or MS-Stable (MSS)) of 14 gastric cancer lines was determined using multiple clone analysis with a panel of five microsatellite markers. Protein levels of hMLH1, hMSH2, hMSH6, hPMS2 and hPMS1 were determined by Western blot. Sequence analysis of hMLH1 and hMSH2 was performed and the methylation status of the hMLH1 promoter was examined. The cell lines SNU1 and SNU638 showed MSI-High, decreased to essentially absent hMLH1 and hPMS2 and reduced hPMS1 and hMSH6 protein levels. The hMLH1 promoter region was hypermethylated in SNU638 cells. The MKN28, MKN87, KATOIII and SNU601 cell lines showed MSI-Low. The MMR protein levels of cells with MSI-Low status was similar to the levels detected in MSS cells. A marked decrease in the expression levels of MutL MMR proteins (hMLH1, hPMS2 and hPMS1) is associated with high levels of MSI mutations in gastric cancer cells. Gastric cancer cell lines with MSI-Low status do not show significant changes in the levels of the main DNA MMR proteins or mutations in the DNA mismatch repair genes hMSH2 and hMLH1. These well-characterized gastric cancer cell lines are a valuable resource to further our understanding of DNA MMR deficiency in cancer development, progression and prognosis. PMID:15133479

  19. Wine and tobacco: risk factors for gastric cancer in France.

    PubMed

    Hoey, J; Montvernay, C; Lambert, R

    1981-06-01

    Cross-sectional studies in France have shown strong regional correlations between death rates from alcohol related diseases and death rates from gastric cancer. The present study involved 40 cases of newly diagnosed adenocarcinoma of the stomach and 168 control subjects with one of four other gastrointestinal diagnoses selected from the same hospital service during the same time period, 1978-1980. On the basis of a standard nutritional interview alcohol and particularly red wine were seen to be significant risk factors for this cancer (relative risks of 6.9 with 95% confidence limits (CL) of 3.3-14.3 for alcohol and 6.3 with CL 3.1-12.7 for wine). Smoking of one or more cigarettes per day was associated with a relative risk for gastric cancer of 4.8 with CL of 1.6-14.8. The presence of both risk factors was associated with a relative risk of 9.3 with 95% CL of 4.6-19.0. Possible confounding by age, smoking, and eating lettuce (a reported protective factor for gastric cancer in other studies) did not explain these results. The relative risks were consistently found and remained significant when each diagnostic group of control subjects was analyzed separately. These results suggest that alcohol, and particularly red wine, may be important risk factors for adenocarcinoma of the stomach in France. In addition, cigarette smoking, a risk factor in itself, when coupled with alcohol appears markedly to increase the risk.

  20. Quality of Life in the Trastuzumab for Gastric Cancer Trial

    PubMed Central

    Bang, Yung-Jue; Gotovkin, Evgeny A.; Hamamoto, Yasuo; Kang, Yoon-Koo; Moiseyenko, Vladimir M.; Ohtsu, Atsushi; Van Cutsem, Eric; Al-Sakaff, Nedal; Urspruch, Alexa; Hill, Julie; Weber, Harald A.; Chung, Hyun-Cheol

    2014-01-01

    Background. The Trastuzumab for Gastric Cancer phase III trial demonstrated that combining trastuzumab with chemotherapy significantly improved overall survival compared with chemotherapy alone in HER2-positive advanced gastric or gastroesophageal junction cancer. We report health-related quality of life (HRQoL) and quality-adjusted time without symptoms of disease or toxicity (Q-TWiST) results from this trial. Patients and Methods. Patients were randomized to receive six cycles of chemotherapy given every 3 weeks (capecitabine or fluorouracil, plus cisplatin) either alone or combined with administration of trastuzumab every 3 weeks until disease progression. At each clinical visit, HRQoL was assessed using two European Organization for Research and Treatment of Cancer quality of life questionnaires, QLQ-C30 and QLQ-STO22. Q-TWiST methodology was applied retrospectively using the clinical data and utility coefficients. Results. Trastuzumab plus chemotherapy prolonged time to 10% definitive deterioration in all QLQ-C30 and QLQ-STO22 scores, including QLQ-C30 global health status versus chemotherapy alone, from 6.4 months to 10.2 months. In addition, trastuzumab plus chemotherapy extended Q-TWiST by 2.42 months compared with chemotherapy alone. Conclusion. Compared with chemotherapy alone, trastuzumab plus chemotherapy prolongs time to deterioration of HRQoL and increases quality-adjusted survival in patients with HER2-positive gastric or gastroesophageal junction cancer. PMID:24951609

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

    PubMed

    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.

  2. IL-32: A Novel Pluripotent Inflammatory Interleukin, towards Gastric Inflammation, Gastric Cancer, and Chronic Rhino Sinusitis.

    PubMed

    Khawar, Muhammad Babar; Abbasi, Muddasir Hassan; Sheikh, Nadeem

    2016-01-01

    A vast variety of nonstructural proteins have been studied for their key roles and involvement in a number of biological phenomenona. Interleukin-32 is a novel cytokine whose presence has been confirmed in most of the mammals except rodents. The IL-32 gene was identified on human chromosome 16 p13.3. The gene has eight exons and nine splice variants, namely, IL-32α, IL-32β, IL-32γ, IL-32δ, IL-32ε, IL-32ζ, IL-32η, IL-32θ, and IL-32s. It was found to induce the expression of various inflammatory cytokines including TNF-α, IL-6, and IL-1β as well as macrophage inflammatory protein-2 (MIP-2) and has been reported previously to be involved in the pathogenesis and progression of a number of inflammatory disorders, namely, inflammatory bowel disease (IBD), gastric inflammation and cancer, rheumatoid arthritis, and chronic obstructive pulmonary disease (COPD). In the current review, we have highlighted the involvement of IL-32 in gastric cancer, gastric inflammation, and chronic rhinosinusitis. We have also tried to explore various mechanisms suspected to induce the expression of this extraordinary cytokine as well as various mechanisms of action employed by IL-32 during the mediation and progression of the above said problems. PMID:27143819

  3. IL-32: A Novel Pluripotent Inflammatory Interleukin, towards Gastric Inflammation, Gastric Cancer, and Chronic Rhino Sinusitis

    PubMed Central

    2016-01-01

    A vast variety of nonstructural proteins have been studied for their key roles and involvement in a number of biological phenomenona. Interleukin-32 is a novel cytokine whose presence has been confirmed in most of the mammals except rodents. The IL-32 gene was identified on human chromosome 16 p13.3. The gene has eight exons and nine splice variants, namely, IL-32α, IL-32β, IL-32γ, IL-32δ, IL-32ε, IL-32ζ, IL-32η, IL-32θ, and IL-32s. It was found to induce the expression of various inflammatory cytokines including TNF-α, IL-6, and IL-1β as well as macrophage inflammatory protein-2 (MIP-2) and has been reported previously to be involved in the pathogenesis and progression of a number of inflammatory disorders, namely, inflammatory bowel disease (IBD), gastric inflammation and cancer, rheumatoid arthritis, and chronic obstructive pulmonary disease (COPD). In the current review, we have highlighted the involvement of IL-32 in gastric cancer, gastric inflammation, and chronic rhinosinusitis. We have also tried to explore various mechanisms suspected to induce the expression of this extraordinary cytokine as well as various mechanisms of action employed by IL-32 during the mediation and progression of the above said problems. PMID:27143819

  4. Slit2 expression and its correlation with subcellular localization of β-catenin in gastric cancer.

    PubMed

    Shi, Rongliang; Liu, Weiyan; Liu, Bingya; Xu, Ziping; Chen, Liping; Zhang, Ziping

    2013-10-01

    Gastric cancer is the fourth most common cancer worldwide. Several signaling pathways are involved in gastric cancer development and progression. Slit2 was recently found to be involved in cancer; however, its expression pattern in gastric cancer has not been discovered yet. In the present study, we investigated the expression of Slit2 in human gastric cancer and its correlation with the expression and subcellular localization of β-catenin. Immunohistochemistry (IHC) staining revealed that Slit2 was highly expressed in human gastric cancer tissues, while it was low or weakly expressed in normal gastric tissues. The differences in clinicopathological features between different groups were determined using Pearson's χ2 test. Slit2 levels were significantly associated with differentiation, Lauren's classification, lymph node metastasis and TNM staging. Slit2 levels were positively correlated with β-catenin level in gastric cancer tissues and cell lines. High levels of Slit2 were correlated with the membrane localization of β-catenin, and low levels of Slit2 were correlated with nuclear translocation of β-catenin in both gastric cancer tissues and cell lines assayed by IHC and immunofluorescence staining, respectively. Our data suggest that Slit2 was highly expressed in gastric cancer patients with less advanced clinicopathological features. Slit2 levels were correlated with β-catenin level and subcellular localization.

  5. [Helicobacter pylori infection and Hyperglycemia/Diabetes are associated with an increased risk of Gastric Cancer].

    PubMed

    Ikeda, Fumie; Kiyohara, Yutaka

    2015-05-01

    Although mortality rates owing to gastric cancer have gradually decreased, the morbidity rates are still high in Japan. Helicobacter pylori(H. pylori)infection is an important risk factor for gastric cancer, although most individuals with an H. pylori infection do not develop this malignancy. Therefore, it is speculated that other risk factors including lifestyle contribute to the enhanced risk of gastric cancer posed by H. pylori infection. It is also noteworthy that the prevalence of prediabetes and diabetes has dramatically increased in Japan, and cancer is now considered a possible complication of the latter. However, there have been very few epidemiological studies evaluating the relationship between diabetes and gastric cancer in Japan. The Hisayama Study, which is a prospective cohort study conducted in a Japanese community, demonstrated that the incidence of gastric cancer significantly increased with elevated fasting plasma glucose levels. A modest increase in hemoglobin A1c levels was also a significant risk factor for gastric cancer even after adjusting for other risk factors, including H. pylori infection. Moreover, among subjects who had both a high hemoglobin A1c level and H. pylori infection, the risk of gastric cancer increased synergistically. These findings suggest that even prediabetic hyperglycemia is a significant risk factor for gastric cancer in the general Japanese population. Early identification of hyperglycemia and an appropriate behavioral and therapeutic approach may help prevent gastric cancer in Japan where there is a high incidence of both this malignancy and diabetes.

  6. Dieulafoy's disease associated with early gastric cancer.

    PubMed Central

    Leone, O; Zanelli, M; Santini, D; Minni, F; Marrano, D

    1995-01-01

    In the past different terms have been used to define the vascular malformations of Dieulafoy's disease--for example, calibre persistent artery of the stomach, cirsoid aneurysm and gastric atherosclerosis. A case of Dieulafoy's disease is described in a 41 year old man, who presented with symptoms of anaemia and melaena, with particular attention paid to the morphological characterisation of the vascular histological lesions. Intimal hyperplasia with a non-concentric proliferation of myointimal cells, areas of muscular degeneration, aspects of vascular neoformation of the arterial wall, and other findings are reported. An association between an early diffuse adenocarcinoma and parietal anomalies of Dieulafoy's disease is illustrated. Images PMID:7730491

  7. [Peppermint oil reduces gastric motility during the upper gastrointestinal endoscopy].

    PubMed

    Hiki, Naoki

    2010-11-01

    Hyperperistalsis during upper gastrointestinal endoscopy may interfere with accurate diagnosis and lead to failure to detect microcarcinoma. Therefore it frequently necessitates the use of antispasmodic agents, but these drugs have side effects. In this review, the author notes note the effectiveness of peppermint oil administration to the gastric mucosa resulted in inhibiting the gastric peristalsis in Japanese individuals undergoing upper gastrointestinal endoscopy.

  8. Gastric cancer in Ardabil, Iran--a review and update on cancer registry data.

    PubMed

    Babaei, Masoud; Pourfarzi, Farhad; Yazdanbod, Abbas; Chiniforush, Mir Mehdi; Derakhshan, Mohammad Hassan; Mousavi, Seyed Mohsen; Samadi, Fatemeh; Rahimi, Giti

    2010-01-01

    The incidence rate of gastric cancer in western countries has shown a remarkable decline in recent years while it is still the most common cancer among men in Iran. Ardabil, a North Western province, was found to have the highest rate of GC in Iran and one of the highest gastric cardia cancer rates in the world. We used the most recent data from Ardabil cancer registry to update on the incidence and mortality of GC and performed an extensive search of the English and Persian literature in Pub Med, Embase and all 5 Persian web-based databases, respectively, to summarize all possible risk factors for GC in Ardabil. The age-standardized incidence rate of gastric cancer was 51.8 (95% CI: 47.8-55.8) in men and 24.9 (95% CI: 21.5-27.2) in women per 100,000. Age-standardized mortality rates for gastric cancer in this population were 32.2 (95% CI: 29.1-35.3) and 16.3 (95% CI: 13.9-18.6). The gastric cardia sub-site was the most common location (32.7%) in Ardabil. According to our review H.pylori infection, gastroesphageal reflux symptoms, tobacco smoking, and high intakes of salt, red meat and dairy products increase the risk of GC while diets with a high content of allium vegetables and fruits, especially citrus fruits, and consumption of fresh fish, were significantly protective against GC. We conclude that Ardabil has the highest rate of GC in Iran and one the highest rates of gastric cardia cancer in the world, with no evidence of decline in incidence since 2000. In addition to H.pylori infection, the epidemic of gastroesphageal reflux disease and several dietary factors may be responsible for the very high incidence of gastric cardia cancer in Ardabil. PMID:21039022

  9. Synergistic tumor suppression by adenovirus-mediated ING4/PTEN double gene therapy for gastric cancer.

    PubMed

    Zhang, H; Zhou, X; Xu, C; Yang, J; Xiang, J; Tao, M; Xie, Y

    2016-01-01

    Both inhibitor of growth 4 (ING4) and phosphatase and tensin homolog (PTEN) have been shown to be strong candidate tumor suppressors. However, the combined efficacy of ING4 and PTEN for human gastric cancer remains to be determined. In this report, we constructed a multiple promoter expression cassette-based recombinant adenovirus coexpressing ING4 and PTEN (AdVING4/PTEN), assessed the combined effects of AdVING4/PTEN on gastric cancer using wild-type p53 AGS and SNU-1 human gastric cancer cell lines, and elucidated its underlying mechanisms. We found that AdVING4/PTEN-induced synergistic growth inhibition and apoptosis in vitro AGS or SNU-1 tumor cells and in vivo AGS xenografted tumors subcutaneously inoculated in athymic BALB/c nude mice. Mechanistically, AdVING4/PTEN exhibited an enhanced effect on upregulation of p53, Ac-p53 (K382), P21, Bax, PUMA, Noxa, cleaved Caspase-9, cleaved Caspase-3 and cleaved PARP as well as downregulation of Bcl-2 in vitro and in vivo. In addition, AdVING4/PTEN synergistically downregulated tumor vessel CD34 expression and reduced microvessel density, and additively inhibited vascular endothelial growth factor (VEGF) expression in vivo. The synergistic tumor suppression elicited by AdVING4/PTEN was closely associated with the synergistic induction of apoptosis possibly via enhancement of endogenous p53 responses through cooperatively facilitating p53's stability and acetylation, and the synergistic inhibition of tumor angiogenesis probably via overlapping reduction of VEGF through cooperatively downregulating hypoxia inducible factor-1α's level and transcription activity. Thus, our results indicate that cancer gene therapy combining ING4 and PTEN may constitute a novel and effective therapeutic modality for human gastric cancer and other cancers.

  10. Frequent amplification of PTP1B is associated with poor survival of gastric cancer patients.

    PubMed

    Wang, Na; She, Junjun; Liu, Wei; Shi, Jing; Yang, Qi; Shi, Bingyin; Hou, Peng

    2015-01-01

    The protein tyrosine phosphatase 1B (PTP1B), a non-transmembrane protein tyrosine phosphatase, has been implicated in gastric pathogenesis. Several lines of recent evidences have shown that PTP1B is highly amplified in breast and prostate cancers. The aim of this study was to investigate PTP1B amplification in gastric cancer and its association with poor prognosis of gastric cancer patients, and further determine the role of PTP1B in gastric tumorigenesis. Our data demonstrated that PTP1B was significantly up-regulated in gastric cancer tissues as compared with matched normal gastric tissues by using quantitative RT-PCR (qRT-PCR) assay. In addition, copy number analysis showed that PTP1B was amplified in 68/131 (51.9%) gastric cancer cases, whereas no amplification was found in the control subjects. Notably, PTP1B amplification was positively associated with its protein expression, and was significantly related to poor survival of gastric cancer patients. Knocking down PTP1B expression in gastric cancer cells significantly inhibited cell proliferation, colony formation, migration and invasion, and induced cell cycle arrested and apoptosis. Mechanically, PTP1B promotes gastric cancer cell proliferation, survival and invasiveness through modulating Src-related signaling pathways, such as Src/Ras/MAPK and Src/phosphatidylinositol-3-kinase (PI3K)/Akt pathways. Collectively, our data demonstrated frequent overexpression and amplification PTP1B in gastric cancer, and further determined the oncogenic role of PTP1B in gastric carcinogenesis. Importantly, PTP1B amplification predicts poor survival of gastric cancer patients. PMID:25590580

  11. The role of interleukin DNA polymorphisms in gastric cancer.

    PubMed

    Yuzhalin, Arseniy

    2011-11-01

    Gastric carcinoma is one of the most widespread malignancies worldwide. Interleukins are the key group of cytokines which may have tumor-promoting or tumor-suppressing effect, and receptors for them, of course, have the same importance in this context. However, mechanisms of their impact on tumor are not fully understood up to date. Numerous studies provide conflicting data, that makes picture more confusing and complicated. It is known that single nucleotide polymorphisms in interleukin genes may dramatically affect on protein expression level, or alter its functions, which may lead to gastritis or ulcer, and eventually promote cancer occurrence. Furthermore, some of these genetic polymorphisms may serve as predictive factors for cancer prognosis and prevention. In order to understand the impact of each genetic polymorphism, the review of IL-1B, IL-4, IL-6, IL-8, IL-10, IL17A, IL-17F DNA polymorphisms on gastric carcinoma was done, and risk alleles were recommended for further research.

  12. Role of periostin in esophageal, gastric and colon cancer

    PubMed Central

    Moniuszko, Tadeusz; Wincewicz, Andrzej; Koda, Mariusz; Domysławska, Izabela; Sulkowski, Stanisław

    2016-01-01

    Periostin, also known as osteoblast-specific factor 2, is a cell-adhesion protein with pleiotropic properties. The protein serves a vital role in the maintenance and development of tooth and bone tissue, in addition to cardiac development and healing. Periostin levels are increased in several forms of cancer, including pancreatic, ovarian, colon, lung, breast, gastric, thyroid, and esophageal head and neck carcinomas. The present review highlights the key role of periostin in tumorigenesis, particularly in increasing cell survival, invasion, angiogenesis, epithelial-mesenchymal transition and metastasis of carcinoma cells by interacting with numerous cell-surface receptors, including integrins, in the phosphoinositide 3-kinase-Akt pathway. In addition, periostin actively affects the canonical Wnt signaling pathway of colorectal tumorigenesis. The current review focused on the involvement of periostin in the development of colorectal, esophageal and gastric cancer. PMID:27446351

  13. Genomics Study of Gastric Cancer and Its Molecular Subtypes.

    PubMed

    Yuen, Siu Tsan; Leung, Suet Yi

    2016-01-01

    Gastric cancer is a heterogeneous disease encompassing diverse morphological (intestinal versus diffuse) and molecular subtypes (MSI, EBV, TP53 mutation). Recent advances in genomic technology have led to an improved understanding of the driver gene mutational profile, gene expression, and epigenetic alterations that underlie each of the subgroups, with therapeutic implications in some of these alterations. There have been attempts to classify gastric cancers based on these genomic features, with an aim to improve prognostication and predict responsiveness to specific drug therapy. The eventual aims of these genomic studies are to develop deep biological insights into the carcinogenic pathway in each of these subtypes. Future large-scale drug screening strategies may then be able to link these genomic features to drug responsiveness, eventually leading to genome-guided personalized medicine with improved cure rates. PMID:27573784

  14. Predictive factors for lymph node metastasis in early gastric cancer

    PubMed Central

    Sung, Chang-Mu; Hsu, Chen-Ming; Hsu, Jun-Te; Yeh, Ta-Sen; Lin, Chun-Jung; Chen, Tse-Ching; Su, Ming-Yao; Chiu, Cheng-Tang

    2010-01-01

    AIM: To analyze the predictive factors for lymph node metastasis (LNM) in early gastric cancer (EGC). METHODS: Data from patients surgically treated for gastric cancers between January 1994 and December 2007 were retrospectively collected. Clinicopathological factors were analyzed to identify predictive factors for LNM. RESULTS: Of the 2936 patients who underwent gastrectomy and lymph node dissection, 556 were diagnosed with EGC and included in this study. Among these, 4.1% of patients had mucosal tumors (T1a) with LNM while 24.3% of patients had submucosal tumors with LNM. Univariate analysis found that female gender, tumors ≥ 2 cm, tumor invasion to the submucosa, vascular and lymphatic involvement were significantly associated with a higher rate of LNM. On multivariate analysis, tumor size, lymphatic involvement, and tumor with submucosal invasion were associated with LNM. CONCLUSION: Tumor with submucosal invasion, size ≥ 2 cm, and presence of lymphatic involvement are predictive factors for LNM in EGC. PMID:21049560

  15. Mitomycin C as an adjuvant in resected gastric cancer.

    PubMed Central

    Alcobendas, F; Milla, A; Estape, J; Curto, J; Pera, C

    1983-01-01

    As a result of their previous experience with mitomycin C at high discontinuous doses in advanced gastric cancer, the authors studied its role as an adjuvant for locally advanced cases after surgical complete resection. Results from 70 evaluable patients are presented. Patients were allocated randomly to receive mitomycin C, 20 mg/m2 I.V. direct once every 6 weeks, four courses, or a placebo. After a follow-up period of 250 weeks, seven patients of treatment arm and 23 controls have already relapsed (p less than 0.001). Toxicity was moderate and controllable by symptomatic measures. The authors consider this investigation a positive contribution in the field of adjuvant therapy of gastric cancer. PMID:6407408

  16. Metformin potentiates rapamycin and cisplatin in gastric cancer in mice

    PubMed Central

    Gao, Yunshu; Jiao, Xiaodong; Huang, Suyun; Wang, Jiejun; Li, Zhaosheng; Xie, Keping

    2015-01-01

    Here we showed that pAMPKα and PTEN were down-regulated and p-mTOR, p-S6, p-4EBP1, MMP7, and DCN1 were up-regulated in human gastric cancer tissue samples as compared to that in the noncancerous tissues. Metformin inhibited tumor growth in mice. Also it enhanced cisplatin- or rapamycin-induced reduction of tumor growth as compared with treatment of either drug alone. In addition to activation of AMPK and suppression of the mTOR pathway, a series of increased and decreased genes expression were induced by metformin, including PTEN, MMP7, and FN1. We suggest that metformin could potentially be used for the treatment of gastric cancer especially in combination with cisplatin or rapamycin. PMID:25909163

  17. Tristetraprolin inhibits gastric cancer progression through suppression of IL-33

    PubMed Central

    Deng, Kaiyuan; Wang, Hao; Shan, Ting; Chen, Yigang; Zhou, Hong; Zhao, Qin; Xia, Jiazeng

    2016-01-01

    Tristetraprolin (TTP) is an adenine/uridine (AU)-rich element (ARE)-binding protein that can induce degradation of mRNAs. In this study, we report that TTP suppresses the expression of interleukin-33 (IL-33), a tumor-promoting inflammatory cytokine, and thereby inhibits the progression of gastric cancer (GC). Overexpression of TTP decreased the level of IL-33, whereas knockdown of TTP increased IL-33 levels. We also discovered that TTP inhibited the proliferation, migration, and invasion of GC cell lines through regulation of IL-33. Furthermore, TTP RNA and protein levels were remarkably reduced in GC and inversely correlated with IL-33 level, and they were also closely associated with depth of invasion, lymph node metastasis, advanced TNM stage, as well as survival rate. Taken together, these findings identified TTP as a downregulator of IL-33, and further suggest that TTP can serve as a novel biomarker for the diagnosis of GC and as a potential therapeutic target for GC treatment. PMID:27074834

  18. A nanomaterial-based breath test for distinguishing gastric cancer from benign gastric conditions

    PubMed Central

    Xu, Z-q; Broza, Y Y; Ionsecu, R; Tisch, U; Ding, L; Liu, H; Song, Q; Pan, Y-y; Xiong, F-x; Gu, K-s; Sun, G-p; Chen, Z-d; Leja, M; Haick, H

    2013-01-01

    Background: Upper digestive endoscopy with biopsy and histopathological evaluation of the biopsy material is the standard method for diagnosing gastric cancer (GC). However, this procedure may not be widely available for screening in the developing world, whereas in developed countries endoscopy is frequently used without major clinical gain. There is a high demand for a simple and non-invasive test for selecting the individuals at increased risk that should undergo the endoscopic examination. Here, we studied the feasibility of a nanomaterial-based breath test for identifying GC among patients with gastric complaints. Methods: Alveolar exhaled breath samples from 130 patients with gastric complaints (37 GC/32 ulcers / 61 less severe conditions) that underwent endoscopy/biopsy were analyzed using nanomaterial-based sensors. Predictive models were built employing discriminant factor analysis (DFA) pattern recognition, and their stability against possible confounding factors (alcohol/tobacco consumption; Helicobacter pylori) was tested. Classification success was determined (i) using leave-one-out cross-validation and (ii) by randomly blinding 25% of the samples as a validation set. Complementary chemical analysis of the breath samples was performed using gas chromatography coupled with mass spectrometry. Results: Three DFA models were developed that achieved excellent discrimination between the subpopulations: (i) GC vs benign gastric conditions, among all the patients (89% sensitivity; 90% specificity); (ii) early stage GC (I and II) vs late stage (III and IV), among GC patients (89% sensitivity; 94% specificity); and (iii) ulcer vs less severe, among benign conditions (84% sensitivity; 87% specificity). The models were insensitive against the tested confounding factors. Chemical analysis found that five volatile organic compounds (2-propenenitrile, 2-butoxy-ethanol, furfural, 6-methyl-5-hepten-2-one and isoprene) were significantly elevated in patients with GC and

  19. Changing pattern of gastric cancer in Oxfordshire.

    PubMed Central

    Rios-Castellanos, E; Sitas, F; Shepherd, N A; Jewell, D P

    1992-01-01

    This study compares the incidence rates of histologically confirmed gastric carcinoma in Oxfordshire in two five year periods (1960-64, 1984-88). Data were available for 215 patients in the first period, and 200 in the second. The overall incidence fell from 18/100,000 to 15/100,000 but when analysed for site, the incidence of antral tumours fell from 10 to 4.5/100,000. In contrast, there was an increase from 2.8 to 5.2/100,000 of tumours of the cardia. These changes were more pronounced in men. There was a marked association between smoking and tumours of the cardia (relative risk 4.5). Helicobacter pylori was associated with 37.5% of tumours in the 1960s series compared with 25% in the later series. The changing patterns of incidence of gastric carcinoma may, in part, be related to changes in smoking habits and perhaps a change in incidence of H pylori infection. Images Figure 2 PMID:1446851

  20. Cytogenetic studies in patients with gastric cancer.

    PubMed

    Abarbanel, J; Shabtai, F; Kyzer, S; Chaimof, C

    1991-01-01

    Banded cytogenetic studies of gastric carcinoma are still relatively scarce, comprised of only a small number of patients. This study was performed on peripheral blood lymphocytes and malignant cells of 16 patients with gastric carcinoma. The lymphocytes were analyzed by standard techniques. All patients had a normal constitutional karyotype; 90% of the patients presented an increased breakage rate and nonrandom chromosomal instability mainly in the heterochromatic regions of chromosomes 1, 9, and 16. Decreased response to phytohemagglutinin was observed in 6 (38%) patients. The tissue specimens were analyzed using direct techniques. Normal ploidy was observed in only one patient, 3 tumors were near-diploid, 4 hyperdiploid, 4 near-triploid, and 4 near-tetraploid. Those with the near-triploid or near-tetraploid constitution were in a more advanced pathological stage, most of them with a more complex cytogenetic profile. Particular involvement was found for chromosomes 1 to 4, 7 to 9, 17, and 20, but the more specific nonrandom changes seemed to involve chromosomes 7, 8, 9, and 17. PMID:1767545

  1. Risk Factors for Gallstone Formation after Surgery for Gastric Cancer

    PubMed Central

    Park, Dong Jin; Kim, Ki Hyun; Park, Young Suk; Ahn, Sang-Hoon; Kim, Hyung-Ho

    2016-01-01

    Purpose The incidence of gallstones after gastrectomy for gastric cancer is higher than in the general population. However, the causes and mechanisms of post-gastrectomy gallstones are unclear. The aim of this study was to evaluate the incidence of gallstone formation and the risk factors for their development after gastrectomy for gastric cancer. Materials and Methods Of 1,744 gastric cancer patients who underwent gastrectomy at Seoul National University Bundang Hospital between January 2010 and December 2012, 1,284 were included in this study and retrospectively reviewed. Patients' age, sex, body mass index (BMI), tumor location, stage, type of gastrectomy, type of reconstruction, and extent of node dissection were evaluated. Results The incidence of gallstones after gastrectomy for gastric cancer was significantly higher in men than in women (P=0.019). Exclusion of the duodenum during reconstruction was associated with a significantly higher incidence of gallstones (P=0.003). Overweight and obese patients with BMI ≥23 kg/m2 had significantly higher incidence of gallstones than those with a lower BMI (P=0.006). Multivariate analysis showed that obesity (hazard ratio, HR=1.614; 95% confidence interval, CI: 1.135~2.296; P=0.008), male sex (HR=1.515, 95% CI: 1.029~2.231, P=0.033), and exclusion of the duodenum (HR=1.648, 95% CI: 1.192~2.280, P=0.003) were significant, independent risk factors for gallstones after gastrectomy. Conclusions The cumulative incidence of gallstones for 5 years after gastrectomy was 15.3%. Male sex, obesity, and exclusion of the duodenum were risk factors for gallstone formation after gastrectomy. Careful surveillance will be required for these patient groups after gastrectomy. PMID:27433395

  2. Clinical significance of lymphadenectomy in patients with gastric cancer

    PubMed Central

    Tóth, Dezső; Plósz, János; Török, Miklós

    2016-01-01

    Approximately thirty percent of patients with gastric cancer undergo an avoidable lymph node dissection with a higher rate of postoperative complication. Comparing the D1 and D2 dissections, it was found that there is a significant difference in morbidity, favoured D1 dissection without any difference in overall survival. Subgroup analysis of patients with T3 tumor shows a survival difference favoring D2 lymphadenectomy, and there is a better gastric cancer-related death and non-statistically significant improvement of survival for node-positive disease in patients with D2 dissection. However, the extended lymphadenectomy could improve stage-specific survival owing to the stage migration phenomenon. The deployment of centralization and application of national guidelines could improve the surgical outcomes. The Japanese and European guidelines enclose the D2 lymphadenectomy as the gold standard in R0 resection. In the individualized, stage-adapted gastric cancer surgery the Maruyama computer program (MCP) can estimate lymph node involvement preoperatively with high accuracy and in addition the Maruyama Index less than 5 has a better impact on survival, than D-level guided surgery. For these reasons, the preoperative application of MCP is recommended routinely, with an aim to perform “low Maruyama Index surgery”. The sentinel lymph node biopsy (SNB) may decrease the number of redundant lymphadenectomy intraoperatively with a high detection rate (93.7%) and an accuracy of 92%. More accurate stage-adapted surgery could be performed using the MCP and SNB in parallel fashion in gastric cancer. PMID:26909128

  3. Dietary patterns and gastric cancer in a Portuguese urban population.

    PubMed

    Bastos, Joana; Lunet, Nuno; Peleteiro, Bárbara; Lopes, Carla; Barros, Henrique

    2010-07-15

    Dietary patterns analysis is a powerful technique to study the relations between diet and cancer. We aimed to quantify the association between dietary patterns and gastric cancer, by location and histological type, according to Helicobacter pylori infection status. We analyzed 591 incident cases of gastric adenocarcinoma and 1,463 community controls. Dietary intake was assessed using a validated food frequency questionnaire. Principal components and cluster analyses were used to define dietary patterns. Anti-H. pylori IgG was assessed by ELISA. Age-, gender-, education- and total energy intake-adjusted odds ratios (OR) were computed. Three dietary patterns were identified, with the following main characteristics: (I) high consumption of fruits and dairy products, and low consumption of alcoholic beverages; (II) low consumption of fruit, salads, vegetables, dairy products, fish and meat; (III) high consumptions of most food groups and low vegetable soup intake. Compared to pattern I, the risk of gastric cancer was higher for pattern II (OR = 1.68, 95% CI: 1.31-2.14) but not for pattern III (OR = 0.80, 95% CI: 0.57-1.14), with no effect modification by H. pylori infection. The association was similar for cardia and non-cardia gastric cancer, but for tumors of the diffuse Laurén histological type, the association was weaker for pattern II vs. I (OR = 1.32, 95% CI: 0.83-2.08) and a protective effect was observed for pattern III vs. I (OR = 0.43, 95% CI: 0.22-0.87). Our results confirm the protective effect of high fruit and vegetables intake, and show a differential association according to histological type. No effect modification by H. pylori infection was observed. PMID:19876925

  4. Silencing NKD2 by promoter region hypermethylation promotes gastric cancer invasion and metastasis by up-regulating SOX18 in human gastric cancer.

    PubMed

    Jia, Yan; Cao, Baoping; Yang, Yunsheng; Linghu, Enqiang; Zhan, Qimin; Lu, Youyong; Yu, Yingyan; Herman, James G; Guo, Mingzhou

    2015-10-20

    Naked cuticle homolog2 (NKD2) is located in chromosome 5p15.3, which is frequently loss of heterozygosity in human colorectal and gastric cancers. In order to understand the mechanism of NKD2 in gastric cancer development, 6 gastric cancer cell lines and 196 cases of human primary gastric cancer samples were involved. Methylation specific PCR (MSP), gene expression array, flow cytometry, transwell assay and xenograft mice model were employed in this study. The expression of NKD1 and NKD2 was silenced by promoter region hypermethylation. NKD1 and NKD2 were methylated in 11.7% (23/196) and 53.1% (104/196) in human primary gastric cancer samples. NKD2 methylation is associated with cell differentiation, TNM stage and distant metastasis significantly (all P < 0.05), and the overall survival time is longer in NKD2 unmethylated group compared to NKD2 methylated group (P < 0.05). Restoration of NKD2 expression suppressed cell proliferation, colony formation, cell invasion and migration, induced G2/M phase arrest, and sensitized cancer cells to docetaxel. NKD2 inhibits SOX18 and MMP-2,7,9 expression and suppresses BGC823 cell xenograft growth. In conclusion, NKD2 methylation may serve as a poor prognostic and chemo-sensitive marker in human gastric cancer. NKD2 impedes gastric cancer metastasis by inhibiting SOX18.

  5. Silencing NKD2 by promoter region hypermethylation promotes gastric cancer invasion and metastasis by up-regulating SOX18 in human gastric cancer

    PubMed Central

    Yang, Yunsheng; Linghu, Enqiang; Zhan, Qimin; Lu, Youyong; Yu, Yingyan; Herman, James G.; Guo, Mingzhou

    2015-01-01

    Naked cuticle homolog2 (NKD2) is located in chromosome 5p15.3, which is frequently loss of heterozygosity in human colorectal and gastric cancers. In order to understand the mechanism of NKD2 in gastric cancer development, 6 gastric cancer cell lines and 196 cases of human primary gastric cancer samples were involved. Methylation specific PCR (MSP), gene expression array, flow cytometry, transwell assay and xenograft mice model were employed in this study. The expression of NKD1 and NKD2 was silenced by promoter region hypermethylation. NKD1 and NKD2 were methylated in 11.7% (23/196) and 53.1% (104/196) in human primary gastric cancer samples. NKD2 methylation is associated with cell differentiation, TNM stage and distant metastasis significantly (all P < 0.05), and the overall survival time is longer in NKD2 unmethylated group compared to NKD2 methylated group (P < 0.05). Restoration of NKD2 expression suppressed cell proliferation, colony formation, cell invasion and migration, induced G2/M phase arrest, and sensitized cancer cells to docetaxel. NKD2 inhibits SOX18 and MMP-2,7,9 expression and suppresses BGC823 cell xenograft growth. In conclusion, NKD2 methylation may serve as a poor prognostic and chemo-sensitive marker in human gastric cancer. NKD2 impedes gastric cancer metastasis by inhibiting SOX18. PMID:26396173

  6. Fra-1 is upregulated in gastric cancer tissues and affects the PI3K/Akt and p53 signaling pathway in gastric cancer.

    PubMed

    He, Junyu; Zhu, Guangchao; Gao, Lu; Chen, Pan; Long, Yuehua; Liao, Shan; Yi, Hong; Yi, Wei; Pei, Zhen; Wu, Minghua; Li, Xiaoling; Xiang, Juanjuan; Peng, Shuping; Ma, Jian; Zhou, Ming; Xiong, Wei; Zeng, Zhaoyang; Xiang, Bo; Tang, Ke; Cao, Li; Li, Guiyuan; Zhou, Yanhong

    2015-11-01

    Gastric cancer is an aggressive disease that continues to have a daunting impact on global health. Fra-1 (FOSL1) plays important roles in oncogenesis in various malignancies. We investigated the expression of Fra-1 in gastric cancer (GC) tissues by qPCR, immunohistochemistry (IHC) and western blot technologies. The results showed that Fra-1 was overexpressed in gastric cancer tissues compared with the adjacent non‑cancerous tissues. To explore the possible mechanism of Fra-1 in GC, we elucidated the effect of Fra-1 in the apoptosis and cell cycle of gastric cancer cells, AGS, and found that a considerable decrease in apoptotic cells and increase of S phase rate were observed for AGS cells with Fra-1 overexpession. We identified and confirmed that Fra-1 affected the expression level of CTTN and EZR in vitro through LC-MS/MS analyses and western blot technology. Furthermore, we found that Fra-1 was correlated with dysregulation PI3K/Akt and p53 signaling pathway in gastric cancer tissues in vitro. Moreover, we found that Fra-1 overexpression affected the expression of PI3K, Akt, MDM2 and p53 in vivo. In summary, our results suggest that Fra-1 is upregulated in gastric cancer tissues and plays its function by affecting the PI3K/Akt and p53 signaling pathway in gastric cancer.

  7. IL-22 produced by cancer-associated fibroblasts promotes gastric cancer cell invasion via STAT3 and ERK signaling

    PubMed Central

    Fukui, H; Zhang, X; Sun, C; Hara, K; Kikuchi, S; Yamasaki, T; Kondo, T; Tomita, T; Oshima, T; Watari, J; Imura, J; Fujimori, T; Sasako, M; Miwa, H

    2014-01-01

    Background: Interleukin-22 (IL-22) has been recently highlighted owing to its biological significance in the modulation of tissue responses during inflammation. However, the role of IL-22 in carcinogenesis has remained unclear. Here, we investigated the pathophysiological significance of IL-22 expression in gastric cancer tissues and examined the mechanism by which IL-22 promotes gastric cancer cell invasion. Methods: Human gastric cancer specimens were analysed by immunohistochemistry for expression of IL-22 and IL-22 receptor 1 (IL-22R1). The effects of IL-22-induced STAT3 and ERK signalling on invasive ability of gastric cancer cells were examined using a small-interfering RNA system and specific inhibitors. AGS cells were co-cultured with cancer-associated fibroblasts (CAFs) from human gastric cancer tissues and assessed by invasion assay. Results: Interleukin-22 and its receptor were expressed in α-smooth muscle actin-positive stromal cells and tumour cells at the invasive front of gastric cancer tissues, respectively. The expression of IL-22 and IL-22R1 was significantly related to lymphatic invasion. Interleukin-22 treatment promoted the invasive ability of gastric cancer cells through STAT3 and ERK activation. The invasive ability of gastric cancer cells was significantly enhanced by co-culture with IL-22-expressing CAFs. Conclusions: Interleukin-22 produced by CAFs promotes gastric cancer cell invasion via STAT3 and ERK signalling. PMID:24937671

  8. Patterns of Response After Preoperative Treatment in Gastric Cancer

    SciTech Connect

    Diaz-Gonzalez, Juan A.; Rodriguez, Javier; Hernandez-Lizoain, Jose L.; Ciervide, Raquel; Gaztanaga, Miren; San Miguel, Inigo; Arbea, Leire; Aristu, J. Javier; Chopitea, Ana; Martinez-Regueira, Fernando; Valenti, Victor; Garcia-Foncillas, Jesus; Martinez-Monge, Rafael; Sola, Jesus J.

    2011-07-01

    Purpose: To analyze the rate of pathologic response in patients with locally advanced gastric cancer treated with preoperative chemotherapy with and without chemoradiation at our institution. Methods and Materials: From 2000 to 2007 patients were retrospectively identified who received preoperative treatment for gastric cancer (cT3-4/ N+) with induction chemotherapy (Ch) or with Ch followed by concurrent chemoradiotherapy (45 Gy in 5 weeks) (ChRT). Surgery was planned 4-6 weeks after the completion of neoadjuvant treatment. Pathologic assessment was used to investigate the patterns of pathologic response after neoadjuvant treatment. Results: Sixty-one patients were analyzed. Of 61 patients, 58 (95%) underwent surgery. The R0 resection rate was 87%. Pathologic complete response was achieved in 12% of the patients. A major pathologic response (<10% of residual tumor) was observed in 53% of patients, and T downstaging was observed in 75%. Median follow-up was 38.7 months. Median disease-free survival (DFS) was 36.5 months. The only patient-, tumor-, and treatment-related factor associated with pathologic response was the use of preoperative ChRT. Patients achieving major pathologic response had a 3-year actuarial DFS rate of 63%. Conclusions: The patterns of pathologic response after preoperative ChRT suggest encouraging intervals of DFS. Such a strategy may be of interest to be explored in gastric cancer.

  9. Trends and predictions for gastric cancer mortality in Brazil

    PubMed Central

    de Souza Giusti, Angela Carolina Brandão; de Oliveira Salvador, Pétala Tuani Candido; dos Santos, Juliano; Meira, Karina Cardoso; Camacho, Amanda Rodrigues; Guimarães, Raphael Mendonça; Souza, Dyego L B

    2016-01-01

    AIM: To analyze the effect of age-period and birth cohort on gastric cancer mortality, in Brazil and across its five geographic regions, by sex, in the population over 20 years of age, as well as make projections for the period 2010-2029. METHODS: An ecological study is presented herein, which distributed gastric cancer-related deaths in Brazil and its geographic regions. The effects of age-period and birth cohort were calculated by the Poisson regression model and projections were made with the age-period-cohort model in the statistical program R. RESULTS: Progressive reduction of mortality rates was observed in the 1980’s, and then higher and lower mortality rates were verified in the 2000’s, for both sexes, in Brazil and for the South, Southeast and Midwest regions. A progressive decrease in mortality rates was observed for the Northeast (both sexes) and North (men only) regions within the period 1995-1999, followed by rising rates. CONCLUSION: Regional differences were demonstrated in the mortality rates for gastric cancer in Brazil, and the least developed regions of the country will present increases in projected mortality rates.

  10. Trends and predictions for gastric cancer mortality in Brazil

    PubMed Central

    de Souza Giusti, Angela Carolina Brandão; de Oliveira Salvador, Pétala Tuani Candido; dos Santos, Juliano; Meira, Karina Cardoso; Camacho, Amanda Rodrigues; Guimarães, Raphael Mendonça; Souza, Dyego L B

    2016-01-01

    AIM: To analyze the effect of age-period and birth cohort on gastric cancer mortality, in Brazil and across its five geographic regions, by sex, in the population over 20 years of age, as well as make projections for the period 2010-2029. METHODS: An ecological study is presented herein, which distributed gastric cancer-related deaths in Brazil and its geographic regions. The effects of age-period and birth cohort were calculated by the Poisson regression model and projections were made with the age-period-cohort model in the statistical program R. RESULTS: Progressive reduction of mortality rates was observed in the 1980’s, and then higher and lower mortality rates were verified in the 2000’s, for both sexes, in Brazil and for the South, Southeast and Midwest regions. A progressive decrease in mortality rates was observed for the Northeast (both sexes) and North (men only) regions within the period 1995-1999, followed by rising rates. CONCLUSION: Regional differences were demonstrated in the mortality rates for gastric cancer in Brazil, and the least developed regions of the country will present increases in projected mortality rates. PMID:27605887

  11. Multimodality management of resectable gastric cancer: A review.

    PubMed

    Shum, Helen; Rajdev, Lakshmi

    2014-10-15

    Adenocarcinoma of the stomach carries a poor prognosis and is the second most common cause of cancer death worldwide. It is recommended that surgical resection with a D1 or a modified D2 gastrectomy (with at least 15 lymph nodes removed for examination) be performed in the United States, though D2 lymphadenectomies should be performed at experienced centers. A D2 lymphadenectomy is the recommended procedure in Asia. Although surgical resection is considered the definitive treatment, rates of recurrences are high, necessitating the need for neoadjuvant or adjuvant therapy. This review article aims to outline and summarize some of the pivotal trials that have defined optimal treatment options for non-metastatic non-cardia gastric cancer. Some of the most notable trials include the INT-0116 trial, which established a benefit in concurrent chemoradiation and adjuvant chemotherapy. This was again confirmed in the ARTIST trial, especially in patients with nodal involvement. Later, the Medical Research Council Adjuvant Gastric Infusional Chemotherapy trial provided evidence for the use of perioperative chemotherapy. Targeted agents such as ramucirumab and trastuzumab are also being investigated for use in locally advanced gastric cancers after demonstrating a benefit in the metastatic setting. Given the poor response rate of this difficult disease to various treatment modalities, numerous studies are currently ongoing in an attempt to define a more effective therapy, some of which are briefly introduced in this review as well.

  12. Interobserver Variation of Clinical Target Volume Delineation in Gastric Cancer

    SciTech Connect

    Jansen, Edwin; Verheij, Marcel

    2010-07-15

    Purpose: To evaluate interobserver variability in clinical target volume (CTV) delineation in gastric cancer performed with the help of a delineation guide. Patients and Methods: Ten radiotherapy centers that participate in the CRITICS Phase III trial were provided with a delineation atlas, preoperative CT scans, a postoperative planning CT scan, and clinical information for a gastric cancer case and were asked to construct a CTV and create a dosimetric plan according to departmental policy. Results: The volumes of the CTVs and planning target volumes (PTVs) differed greatly, with a mean (SD) CTV volume of 392 (176) cm{sup 3} (range, 240-821cm{sup 3}) and PTV volume of 915 (312) cm{sup 3} (range, 634-1677cm{sup 3}). The overlapping volume was 376cm{sup 3} for the CTV and 890cm{sup 3} for the PTV. The greatest differences in the CTV were seen at the cranial and caudal parts. After planning, dose coverage of the overlapping PTV volume showed less variability than the CTV. Conclusion: In this series of 10 plans, variability of the CTV in postoperative chemoradiotherapy for gastric cancer is large. Strict and clear delineation guidelines should be provided, especially in Phase III multicenter studies. Adaptations of these guidelines should be evaluated in clinical studies.

  13. Contributions of phosphatidylserine-positive platelets and leukocytes and microparticles to hypercoagulable state in gastric cancer patients.

    PubMed

    Yang, Chunfa; Ma, Ruishuang; Jiang, Tao; Cao, Muhua; Zhao, Liangliang; Bi, Yayan; Kou, Junjie; Shi, Jialan; Zou, Xiaoming

    2016-06-01

    Hypercoagulability in gastric cancer is a common complication and a major contributor to poor prognosis. This study aimed to determine procoagulant activity of blood cells and microparticles (MPs) in gastric cancer patients. Phosphatidylserine-positive blood cells and MPs, and their procoagulant properties in particular, were assessed in 48 gastric cancer patients and 35 healthy controls. Phosphatidylserine-positive platelets, leukocytes, and MPs in patients with tumor-node-metastasis stage III/IV gastric cancer were significantly higher than those in stage I/II patients or healthy controls. Moreover, procoagulant activity of platelets, leukocytes, and MPs in stage III/IV patients was significantly increased compared to the controls, as indicated by shorter clotting time, higher intrinsic and extrinsic factor tenase, and prothrombinase complex activity. Interestingly, lactadherin, which competes with factors V and VIII to bind phosphatidylserine, dramatically prolonged clotting time of the cells and MPs by inhibiting factor tenase and prothrombinase complex activity. Although anti-tissue factor antibody significantly attenuated extrinsic tenase complex activity of leukocytes and MPs, it only slightly prolonged clotting times. Meanwhile, treatment with radical resection reduced phosphatidylserine-positive platelets, leukocytes, and MPs, and prolonged the clotting times of the remaining cells and MPs. Our results suggest that phosphatidylserine-positive platelets, leukocytes, and MPs contribute to hypercoagulability and represent a potential therapeutic target to prevent coagulation in patients with stage III/IV gastric cancer.

  14. Preoperative radiotherapy in gastric cancer: CTV definition for conformal therapy according to tumor location.

    PubMed

    Cellini, Francesco; Valentini, Vincenzo; Pacelli, Fabio; D'Ugo, Domenico; Mantini, Giovanna; Balducci, Mario; Gambacorta, Maria Antonietta; Nori, Stefania

    2003-01-01

    In the past radiation oncologists had not a major interest in the treatment of gastric cancer, but the positive outcomes of the Intergroup Study (INT-0116) supported the role of locoregional control in promoting better survival. To reduce the toxicity and the risk of residual disease in locally advanced tumors after surgery,a preoperative approach was tentatively considered. The aim of this manuscript is to define the location of nodal area at risk for cancer involvement according to the tumor location (cardias, corpus, antrum) on CT images to help the radiotherapist in the contouring process of the CTV for preoperative conformal treatment of gastric cancer. The analysis of both the percentage of nodal involvement detected at surgery and of the site of recurrence after radical surgery can direct to the areas to be considered at risk with its contouring on CT. Preoperative conformal-three dimensional radiotherapy of gastric cancer requires clear and well defined contouring guide-lines to allow the evaluation of clinical outcomes and the analysis if the area at risk for recurrence has changed after the preoperative approach. PMID:15018320

  15. Gastric ulcer patients are more susceptible to developing gastric cancer compared with concomitant gastric and duodenal ulcer patients

    PubMed Central

    HONG, JUN-BO; ZUO, WEI; WANG, AN-JIANG; XU, SHAN; TU, LU-XIA; CHEN, YOU-XIANG; ZHU, XUAN; LU, NONG-HUA

    2014-01-01

    Intestinal metaplasia (IM) and dysplasia are precancerous lesions of gastric cancer (GC); however, the prevalence of IM and dysplasia in patients exhibiting single gastric ulcer (GU) and concomitant gastric and duodenal ulcer (CGDU) varies. In the present study consecutive patients who had undergone esophagogastroduodenal endoscopy were retrospectively screened, and those presenting with GU or CGDU were further evaluated for IM and dysplasia. Patients diagnosed with GC or lymphoma and patients with a history of anti-Helicobacter pylori, non-steroidal anti-inflammatory medicine (NSAIM), H2-receptor antagonist or proton pump inhibitor therapy, were excluded from the present study. Of the 204,073 consecutively screened cases, 8,855 (4.3%) and 2,397 (1.2%) were diagnosed with GU and CGDU, respectively. A total of 1,722 GU and 233 CGDU patients were excluded; thus, 7,133 and 2,164 cases of GU and CGDU, respectively (n=9,297), were included in the present study. IM and dysplasia were observed in 1,348 (14.5%) and 210 (2.3%) patients, respectively. IM was more frequently identified in GU patients compared with CGDU patients (16.4 vs. 8.3%; odds ratio [OR], 2.158; 95% confidence interval [CI], 1.830–2.545; χ2=86.932; P<0.001); furthermore, GU patients exhibited significantly more frequent IM compared with CGDU patients at the gastric antrum (14.2 vs. 5.5%; OR, 2.818; 95% CI, 2.199–3.610; χ2=72.299; P<0.001), gastric incisura (24.0 vs. 14.1%; OR, 1.922; 95% CI, 1.502–2.432; χ2=30.402; P<0.001) and gastric corpus (12.6 vs. 3.3%; OR, 4.259; 95% CI, 1.030–17.609; χ2=4.736; P=0.026). Dysplasia was significantly more frequently identified in GU patients compared with CGDU patients (2.7 vs. 0.7%; OR, 4.027; 95% CI, 2.376–6.823; χ2=31.315; P<0.001), with GU patients exhibiting significantly more severe dysplasia at the gastric antrum (2.4 vs. 0.7%; OR, 3.339; 95% CI, 1.735–6.425; χ2=14.652; P<0.001) and the gastric incisura (2.9 vs. 0.7%; OR, 4.255; 95% CI, 1

  16. The Inositide Signaling Pathway As a Target for Treating Gastric Cancer and Colorectal Cancer

    PubMed Central

    Kim, Hong Jun; Lee, Suk-young; Oh, Sang Cheul

    2016-01-01

    Gastric cancer and colorectal cancer are the leading cause of cancer mortality and have a dismal prognosis. The introduction of biological agents to treat these cancers has resulted in improved outcomes, and combination chemotherapy with targeted agents and conventional chemotherapeutic agents is regarded as standard therapy. Additional newly clarified mechanisms of oncogenesis and resistance to targeted agents require the development of new biologic agents. Aberrant activation of the inositide signaling pathway by a loss of function PTEN mutation or gain of function mutation/amplification of PIK3CA is an oncogenic mechanism in gastric cancer and colorectal cancer. Clinical trials with biologic agents that target the inositide signaling pathway are being performed to further improve treatment outcomes of patients with advanced gastric cancer and metastatic colorectal cancer (CRC). In this review we summarize the inositide signaling pathway, the targeted agents that inhibit abnormal activation of this signaling pathway and the clinical trials currently being performed in patients with advanced or metastatic gastric cancer and metastatic CRC using these targeted agents. PMID:27242542

  17. CDK4/6 inhibitor suppresses gastric cancer with CDKN2A mutation

    PubMed Central

    Huang, Shiliang; Ye, Hua; Guo, Wenying; Dong, Xianwen; Wu, Nali; Zhang, Xie; Huang, Zhigang

    2015-01-01

    Aim: Gastric cancer is a major health problem and current treatment lacks lasting effect. Targeted therapy for gastric cancer with specific genetic background is in urgent need. Methods: We have studied The Cancer Genomic Atlas (TCGA) and The Genomics of Drug Sensitivity in Cancer (GDSC) databases to reveal genes with high frequency of mutation and possible sensitive compound against such gene mutation. In vitro studies were conducted to validate the in silico findings. Results: CDKN2A is frequently mutated in gastric cancer, revealed in TCGA database. CDK4/6 inhibitor PD-0332991 was sensitive in cancer cells with CDKN2A mutation, revealed in GDSC database. In vitro studies showed that PD-0332991 could selectively inhibit proliferation of gastric cancer cell with CDKN2A mutation. PD-0332991 could also inhibit cell invasion, migration, and colony formation of gastric cancer cell with CDKN2A mutation. PD-0332991 induced cell cycle arrest but not apoptosis. PD-0332991 inhibited xenograft gastric cancer mouse model. Conclusion: Gastric cancer with CDKN2A mutation is sensitive to CDK4/6 inhibitor. PD-0332991 is a potential therapeutic agent for gastric cancer. PMID:26380006

  18. Gastric cancer development after the successful eradication of Helicobacter pylori

    PubMed Central

    Uno, Kaname; Iijima, Katsunori; Shimosegawa, Tooru

    2016-01-01

    Gastric cancer (GC) develops as a result of inflammation-associated carcinogenesis due to Helicobacter pylori (H. pylori) infection and subsequent defects in genetic/epigenetic events. Although the indication for eradication therapy has become widespread, clinical studies have revealed its limited effects in decreasing the incidence of GC. Moreover, research on biopsy specimens obtained by conventional endoscopy has demonstrated the feasibility of the restoration of some genetic/epigenetic alterations in the gastric mucosa. Practically, the number of sporadic cases of primary/metachronous GC that emerge after successful eradication has increased, while on-going guidelines recommend eradication therapy for patients with chronic gastritis and those with background mucosa after endoscopic resection for GC. Accordingly, regular surveillance of numerous individuals who have received eradication therapy is recommended despite the lack of biomarkers. Recently, the focus has been on functional reversibility after successful eradication as another cue to elucidate the mechanisms of restoration as well as those of carcinogenesis in the gastric mucosa after H. pylori eradication. We demonstrated that Congo-red chromoendoscopy enabled the identification of the multi-focal distribution of functionally irreversible mucosa compared with that of restored mucosa after successful eradication in individuals at extremely high risk for GC. Further research that uses functional imaging may provide new insights into the mechanisms of regeneration and carcinogenesis in the gastric mucosa post-eradication and may allow for the development of useful biomarkers. PMID:26989462

  19. Current status of function-preserving surgery for gastric cancer

    PubMed Central

    Saito, Takuro; Kurokawa, Yukinori; Takiguchi, Shuji; Mori, Masaki; Doki, Yuichiro

    2014-01-01

    Recent advances in diagnostic techniques have allowed the diagnosis of gastric cancer (GC) at an early stage. Due to the low incidence of lymph node metastasis and favorable prognosis in early GC, function-preserving surgery which improves postoperative quality of life may be possible. Pylorus-preserving gastrectomy (PPG) is one such function-preserving procedure, which is expected to offer advantages with regards to dumping syndrome, bile reflux gastritis, and the frequency of flatus, although PPG may induce delayed gastric emptying. Proximal gastrectomy (PG) is another function-preserving procedure, which is thought to be advantageous in terms of decreased duodenogastric reflux and good food reservoir function in the remnant stomach, although the incidence of heartburn or gastric fullness associated with this procedure is high. However, these disadvantages may be overcome by the reconstruction method used. The other important problem after PG is remnant GC, which was reported to occur in approximately 5% of patients. Therefore, the reconstruction technique used with PG should facilitate postoperative endoscopic examinations for early detection and treatment of remnant gastric carcinoma. Oncologic safety seems to be assured in both procedures, if the preoperative diagnosis is accurate. Patient selection should be carefully considered. Although many retrospective studies have demonstrated the utility of function-preserving surgery, no consensus on whether to adopt function-preserving surgery as the standard of care has been reached. Further prospective randomized controlled trials are necessary to evaluate survival and postoperative quality of life associated with function-preserving surgery. PMID:25516640

  20. Immunological battlefield in gastric cancer and role of immunotherapies

    PubMed Central

    Wang, Minyu; Busuttil, Rita A; Pattison, Sharon; Neeson, Paul J; Boussioutas, Alex

    2016-01-01

    Like the wars predating the First World War where human foot soldiers were deemed tools in the battlefield against an enemy, so too are the host immune cells of a patient battling a malignant gastric cancer. Indeed, the tumour microenvironment resembles a battlefield, where the patient’s immune cells are the defence against invading tumour cells. However, the relationship between different immune components of the host response to cancer is more complex than an “us against them” model. Components of the immune system inadvertently work against the interests of the host and become pro-tumourigenic while other components soldier on against the common enemy – the tumour cell.

  1. Immunological battlefield in gastric cancer and role of immunotherapies.

    PubMed

    Wang, Minyu; Busuttil, Rita A; Pattison, Sharon; Neeson, Paul J; Boussioutas, Alex

    2016-07-28

    Like the wars predating the First World War where human foot soldiers were deemed tools in the battlefield against an enemy, so too are the host immune cells of a patient battling a malignant gastric cancer. Indeed, the tumour microenvironment resembles a battlefield, where the patient's immune cells are the defence against invading tumour cells. However, the relationship between different immune components of the host response to cancer is more complex than an "us against them" model. Components of the immune system inadvertently work against the interests of the host and become pro-tumourigenic while other components soldier on against the common enemy - the tumour cell. PMID:27605873

  2. Study of gastric cancer samples using terahertz techniques

    NASA Astrophysics Data System (ADS)

    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.

  3. Sentinel Lymph Node Navigation Surgery for Early Gastric Cancer: Is It a Safe Procedure in Countries with Non-Endemic Gastric Cancer Levels? A Preliminary Experience

    PubMed Central

    Dos Santos, Elizabeth Gomes; Victer, Felipe Carvalho; Neves, Marcelo Soares; Pinto, Márcia Ferreira; Carvalho, Carlos Eduardo De Souza

    2016-01-01

    Purpose Early diagnosis of gastric cancer is still the exception in Western countries. In the East, as in Japan and Korea, this disease is an endemic disorder. More conservative surgical procedures are frequently performed in early gastric cancer cases in these countries where sentinel lymph node navigation surgery is becoming a safe option for some patients. This study aims to evaluate preliminary outcomes of patients with early gastric cancer who underwent sentinel node navigation surgeries in Brazil, a country with non-endemic gastric cancer levels. Materials and Methods From September 2008 to March 2014, 14 out of 205 gastric cancer patients underwent sentinel lymph node navigation surgeries, which were performed using intraoperative, endoscopic, and peritumoral injection of patent blue dye. Results Antrectomies with Billroth I gastroduodenostomies were performed in seven patients with distal tumors. The other seven patients underwent wedge resections. Sentinel basin resections were performed in four patients, and lymphadenectomies were extended to stations 7, 8, and 9 in the other 10. Two patients received false-negative results from sentinel node biopsies, and one of those patients had micrometastasis. There was one postoperative death from liver failure in a cirrhotic patient. Another cirrhotic patient died after two years without recurrence of gastric cancer, also from liver failure. All other patients were followed-up for 13 to 79 months with no evidence of recurrence. Conclusions Sentinel lymph node navigation surgery appears to be a safe procedure in a country with non-endemic levels of gastric cancer. PMID:27104022

  4. Biomarkers for gastric cancer: Progression in early diagnosis and prognosis (Review)

    PubMed Central

    JIN, ZILIANG; JIANG, WEIHUA; WANG, LIWEI

    2015-01-01

    Gastric cancer is one of leading causes of cancer-related mortality worldwide and is a notable disease due to its heterogeneity. Recently, numerous studies have investigated the molecular basis of gastric cancer, involving the alteration of pathogenesis, and invasion and metastasis. With the development of modern technologies, various novel biomarkers had been identified that appear to possess diagnostic and prognostic value; therefore, the present review describes our current knowledge of biomarkers for the early diagnosis and prognosis of gastric cancer. Classic biomarkers for gastric cancer diagnosis include carcinoembryonic antigen and cancer antigen 19-9, while microRNA and DNA hypomethylation are proposed as novel biomarkers. Excluding classical biomarkers, biomarkers for determining the progression and prognosis of gastric cancer focus on targeting microRNAs, epigenetic alterations and genetic polymorphisms. PMID:25788990

  5. Early or late antibiotic intervention prevents Helicobacter pylori-induced gastric cancer in a mouse model.

    PubMed

    Zhang, Songhua; Lee, Dong Soo; Morrissey, Rhiannon; Aponte-Pieras, Jose R; Rogers, Arlin B; Moss, Steven F

    2014-12-01

    H. pylori infection causes gastritis, peptic ulcers and gastric cancer. Eradicating H. pylori prevents ulcers, but to what extent this prevents cancer remains unknown, especially if given after intestinal metaplasia has developed. H. pylori infected wild-type (WT) mice do not develop cancer, but mice lacking the tumor suppressor p27 do so, thus providing an experimental model of H. pylori-induced cancer. We infected p27-deficient mice with H. pylori strain SS1 at 6-8 weeks of age. Persistently H. pylori-infected WT C57BL/6 mice served as controls. Mice in the eradication arms received antimicrobial therapy (omeprazole, metronidazole and clarithromycin) either "early" (at 15 weeks post infection, WPI) or "late" at 45 WPI. At 70 WPI, mice were euthanized for H. pylori determination, histopathology and cytokine/chemokine expression. Persistently infected mice developed premalignant lesions including high-grade dysplasia, whereas those given antibiotics did not. Histologic activity scores in the eradication groups were similar to each other, and were significantly decreased compared with controls for inflammation, epithelial defects, hyperplasia, metaplasia, atrophy and dysplasia. IP-10 and MIG levels in groups that received antibiotics were significantly lower than controls. There were no significant differences in expression of IFN-γ, TNF-α, IL-1β, RANTES, MCP-1, MIP-1α or MIP-1β among the three groups. Thus, H. pylori eradication given either early or late after infection significantly attenuated gastric inflammation, gastric atrophy, hyperplasia, and dysplasia in the p27-deficient mice model of H. pylori-induced gastric cancer, irrespective of the timing of antibiotic administration. This was associated with reduced expression of IP-10 and MIG.

  6. Prognostic values of four Notch receptor mRNA expression in gastric cancer

    PubMed Central

    Wu, Xiaoyu; Liu, Wentao; Tang, Ding; Xiao, Haijuan; Wu, Zhenfeng; Chen, Che; Yao, Xuequan; Liu, Fukun; Li, Gang

    2016-01-01

    Notch ligands and receptors are frequently deregulated in several human malignancies including gastric cancer. The activation of Notch signaling has been reported to contribute to gastric carcinogenesis and progression. However, the prognostic roles of individual Notch receptors in gastric cancer patients remain elusive. In the current study, we accessed the prognostic roles of four Notch receptors, Notch 1–4, in gastric cancer patients through “The Kaplan-Meier plotter” (KM plotter) database, in which updated gene expression data and survival information include a total of 876 gastric cancer patients. All four Notch receptors’ high mRNA expression was found to be correlated to worsen overall survival (OS) for all gastric cancer patients followed for 20 years. We further accessed the prognostic roles of individual Notch receptors in different clinicopathological features using Lauren classification, pathological grades, clinical grades, HER2 status and different choices of treatments of gastric cancer patients. These results indicate that there are critical prognostic values of the four Notch receptors in gastric cancer. This information will be useful for better understanding of the heterogeneity and complexity in the molecular biology of gastric cancer and to develop tools to more accurately predict their prognosis. PMID:27363496

  7. Deregulated Expression of SRC, LYN and CKB Kinases by DNA Methylation and Its Potential Role in Gastric Cancer Invasiveness and Metastasis.

    PubMed

    Mello, Adriano Azevedo; Leal, Mariana Ferreira; Rey, Juan Antonio; Pinto, Giovanny Rebouças; Lamarão, Leticia Martins; Montenegro, Raquel Carvalho; Alves, Ana Paula Negreiros Nunes; Assumpção, Paulo Pimentel; Borges, Barbara do Nascimento; Smith, Marília Cardoso; Burbano, Rommel Rodriguez

    2015-01-01

    Kinases are downstream modulators and effectors of several cellular signaling cascades and play key roles in the development of neoplastic disease. In this study, we aimed to evaluate SRC, LYN and CKB protein and mRNA expression, as well as their promoter methylation, in gastric cancer. We found elevated expression of SRC and LYN kinase mRNA and protein but decreased levels of CKB kinase, alterations that may have a role in the invasiveness and metastasis of gastric tumors. Expression of the three studied kinases was also associated with MYC oncogene expression, a possible biomarker for gastric cancer. To understand the mechanisms that regulate the expression of these genes, we evaluated the DNA promoter methylation of the three kinases. We found that reduced SRC and LYN methylation and increased CKB methylation was associated with gastric cancer. The reduced SRC and LYN methylation was associated with increased levels of mRNA and protein expression, suggesting that DNA methylation is involved in regulating the expression of these kinases. Conversely, reduced CKB methylation was observed in samples with reduced mRNA and protein expression, suggesting CKB expression was found to be only partly regulated by DNA methylation. Additionally, we found that alterations in the DNA methylation pattern of the three studied kinases were also associated with the gastric cancer onset, advanced gastric cancer, deeper tumor invasion and the presence of metastasis. Therefore, SRC, LYN and CKB expression or DNA methylation could be useful markers for predicting tumor progression and targeting in anti-cancer strategies.

  8. Helicobacter pylori Antibody Titer and Gastric Cancer Screening

    PubMed Central

    Kishikawa, Hiroshi; Kimura, Kayoko; Takarabe, Sakiko; Kaida, Shogo; Nishida, Jiro

    2015-01-01

    The “ABC method” is a serum gastric cancer screening method, and the subjects were divided based on H. pylori serology and atrophic gastritis as detected by serum pepsinogen (PG): Group A [H. pylori (−) PG (−)], Group B [H. pylori (+) PG (−)], Group C [H. pylori (+) PG (+)], and Group D [H. pylori (−) PG (+)]. The risk of gastric cancer is highest in Group D, followed by Groups C, B, and A. Groups B, C, and D are advised to undergo endoscopy, and the recommended surveillance is every three years, every two years, and annually, respectively. In this report, the reported results with respect to further risk stratification by anti-H. pylori antibody titer in each subgroup are reviewed: (1) high-negative antibody titer subjects in Group A, representing posteradicated individuals with high risk for intestinal-type cancer; (2) high-positive antibody titer subjects in Group B, representing active inflammation with high risk for diffuse-type cancer; and (3) low-positive antibody titer subjects in Group C, representing advanced atrophy with increased risk for intestinal-type cancer. In these subjects, careful follow-up with intervals of surveillance of every three years in (1), every two years in (2), and annually in (3) should be considered. PMID:26494936

  9. Is screening and surveillance for early detection of gastric cancer needed in Korean Americans?

    PubMed Central

    Kim, Gwang Ha; Bang, Sung Jo; Ende, Alexander R.; Hwang, Joo Ha

    2015-01-01

    The incidence rate of gastric cancer in Korean Americans is over five times higher than that in non-Hispanic whites, and is similar to the incidence of colorectal cancer in the overall United States population. In Korea, the National Cancer Screening Program recommends endoscopy or upper gastrointestinal series for people aged 40 years and older every 2 years. However, the benefit of gastric cancer screening in Korean Americans has not been evaluated. Based on epidemiologic studies, Korean Americans appear to have more similar gastric cancer risk factors to Koreans as opposed to Americans of European descent, though the risk of gastric cancer appears to decrease for subsequent generations. Therefore, in accordance with recent recommendations regarding screening for gastric cancer in Korea, endoscopic screening for gastric cancer in Korean Americans should be considered, especially in those with known atrophic gastritis/intestinal metaplasia or a family history of gastric cancer. In the future, additional studies will needed to assess whether a screening program for gastric cancer in Korean Americans will result in a survival benefit. PMID:26552450

  10. Oral glutathione supplementation drastically reduces Helicobacter-induced gastric pathologies

    PubMed Central

    De Bruyne, Ellen; Ducatelle, Richard; Foss, Dennis; Sanchez, Margaret; Joosten, Myrthe; Zhang, Guangzhi; Smet, Annemieke; Pasmans, Frank; Haesebrouck, Freddy; Flahou, Bram

    2016-01-01

    Helicobacter (H.) suis causes gastric pathologies in both pigs and humans. Very little is known on the metabolism of this bacterium and its impact on the host. In this study, we have revealed the importance of the glutamate-generating metabolism, as shown by a complete depletion of glutamine (Gln) in the medium during H. suis culture. Besides Gln, H. suis can also convert glutathione (GSH) to glutamate, and both reactions are catalyzed by the H. suis γ-glutamyltranspeptidase (GGT). Both for H. pylori and H. suis, it has been hypothesized that the degradation of Gln and GSH may lead to a deficiency for the host, possibly initiating or promoting several pathologies. Therefore the in vivo effect of oral supplementation with Gln and GSH was assessed. Oral supplementation with Gln was shown to temper H. suis induced gastritis and epithelial (hyper)proliferation in Mongolian gerbils. Astonishingly, supplementation of the feed with GSH, another GGT substrate, resulted in inflammation and epithelial proliferation levels returning to baseline levels of uninfected controls. This indicates that Gln and GSH supplementation may help reducing tissue damage caused by Helicobacter infection in both humans and pigs, highlighting their potential as a supportive therapy during and after Helicobacter eradication therapy. PMID:26833404

  11. Solitary AFP- and PIVKA-II-producing hepatoid gastric cancer with giant lymph node metastasis.

    PubMed

    Iso, Yukihiro; Sawada, Tokihiko; Shimoda, Mitsugi; Rokkaku, Kyu; Ohkura, Yasuo; Kubota, Keiichi

    2005-01-01

    A 61-year-old man was admitted to our hospital because of abdominal pain and an abdominal mass. The patient had anemia and elevated serum alpha-fetoprotein (AFP) (9630ng/mL) and PIVKA-II (91mAU/mL) levels. Roentgenographic examination revealed an extra-gastric tumor in the upper abdomen, and gastroscopy revealed Bormann type 2 gastric cancer in the lower portion of the stomach. The preoperative diagnosis was synchronous gastric cancer and hepatocellular carcinoma (HCC), and surgery was performed. The extra-gastric tumor appeared to be an extra-hepatically growing HCC because the tumor was fed by vessels ramifying from the umbilical portion of the liver. Distal gastrectomy with resection of the extra-gastric tumor was performed, and histological examination of the resected specimen revealed that the gastric cancer was an AFP-producing hepatoid gastric adenocarcinoma and that the extra-gastric tumor was a lymph node metastasis. AFP-producing hepatoid gastric adenocarcinoma tends to metastasize to the regional lymph nodes and form a giant tumor. A giant tumor in the upper abdomen associated with gastric cancer may therefore be a clinical manifestation of AFP-producing hepatoid gastric adenocarcinoma.

  12. Long non-coding RNA Linc00152 is involved in cell cycle arrest, apoptosis, epithelial to mesenchymal transition, cell migration and invasion in gastric cancer

    PubMed Central

    Zhao, Jing; Liu, Yongchao; Zhang, Wenhong; Zhou, Zhongwen; Wu, Jing; Cui, Peng; Zhang, Ying; Huang, Guangjian

    2015-01-01

    Gastric cancer remains a serious threat to public health with high incidence and mortality worldwide. Accumulating evidence demonstrates that long non-coding RNAs (lncRNAs) play important roles in regulating gene expression and are involved in various pathological processes, including gastric cancer. To investigate the possible role of dysregulated lncRNAs in gastric cancer development, we performed lncRNA microarray and identified 3141 significantly differentially expressed lncRNAs in gastric cancer tissues. Next, some of deregulated lncRNAs were validated among about 60 paired gastric cancer specimens such as Linc00261, DKFZP434K028, RPL34-AS1, H19, HOTAIR and Linc00152. Our results found that the decline of DKFZP434K028 and RPL34-AS1, and the increased expression of Linc00152 positively correlated with larger tumor size. The high expression levels of HOTAIR were associated with lymphatic metastasis and poor differentiation. Since the biological roles of Linc00152 are largely unknown in gastric cancer pathogenesis, we assessed its functions by silencing its up-regulation in gastric cancer cells. We found that Linc00152 knockdown could inhibit cell proliferation and colony formation, promote cell cycle arrest at G1 phase, trigger late apoptosis, reduce the epithelial to mesenchymal transition (EMT) program, and suppress cell migration and invasion. Taken together, we delineate the gastric cancer lncRNA signature and demonstrate the oncogenic functions of Linc00152. These findings may have implications for developing lncRNA-based biomarkers for diagnosis and therapeutics for gastric cancer. PMID:26237576

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

    PubMed

    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 e