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Sample records for age 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. Patients with Old Age or Proximal Tumors Benefit from Metabolic Syndrome in Early Stage Gastric Cancer

    PubMed Central

    Zhang, Ying; Liu, Jian-xin; Yu, Hong-mei; Liang, Wei-ping; Jin, Ying; Ren, Chao; He, Ming-ming; Chen, Wei-wei; Luo, Hui-yan; Wang, Zhi-qiang; Zhang, Dong-sheng; Wang, Feng-hua; Li, Yu-hong; Xu, Rui-hua

    2014-01-01

    Background Metabolic syndrome and/or its components have been demonstrated to be risk factors for several cancers. They are also found to influence survival in breast, colon and prostate cancer, but the prognostic value of metabolic syndrome in gastric cancer has not been investigated. Methods Clinical data and pre-treatment information of metabolic syndrome of 587 patients diagnosed with early stage gastric cancer were retrospectively collected. The associations of metabolic syndrome and/or its components with clinical characteristics and overall survival in early stage gastric cancer were analyzed. Results Metabolic syndrome was identified to be associated with a higher tumor cell differentiation (P = 0.036). Metabolic syndrome was also demonstrated to be a significant and independent predictor for better survival in patients aged >50 years old (P = 0.009 in multivariate analysis) or patients with proximal gastric cancer (P = 0.047 in multivariate analysis). No association was found between single metabolic syndrome component and overall survival in early stage gastric cancer. In addition, patients with hypertension might have a trend of better survival through a good control of blood pressure (P = 0.052 in univariate analysis). Conclusions Metabolic syndrome was associated with a better tumor cell differentiation in patients with early stage gastric cancer. Moreover, metabolic syndrome was a significant and independent predictor for better survival in patients with old age or proximal tumors. PMID:24599168

  3. [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.

  4. Gastric Microbiome and Gastric Cancer

    PubMed Central

    Brawner, Kyle M.; Morrow, Casey D.; Smith, Phillip D.

    2014-01-01

    Cancer of the stomach is the fourth most common cancer worldwide. The single strongest risk factor for gastric cancer is Helicobacter pylori-associated chronic gastric inflammation. Among persons with H. pylori infection, strain-specific components, host immune responses, and environmental factors influence the risk for gastric disease, including adenocarcinoma of the stomach, although only a small proportion of infected persons develop the malignancy. Recent advances in DNA sequencing technology have uncovered a complex community of non-cultivatable inhabitants of the human stomach. The interaction between these inhabitants, collectively referred to as the gastric microbiota, and H. pylori likely impacts gastric immunobiology and possibly the sequelae of H. pylori infection. Thus, characterization of the gastric microbiota in subjects with and without H. pylori infection could provide new insight into gastric homeostasis and the pathogenesis of H. pylori-associated disease, including gastric cancer. PMID:24855010

  5. Differences in the prognosis of early gastric cancer according to sex and age

    PubMed Central

    Suh, Do Dam; Oh, Seong Tae; Yook, Jeong Hwan; Kim, Byung-Sik; Kim, Beom Su

    2016-01-01

    Background: Few studies have compared early gastric cancer (EGC) outcomes according to sex and age. Methods: We retrospectively reviewed 2085 patients who underwent curative gastrectomy for EGC between 1989 and 2000. Prognosis and risk factors for nodal involvement were evaluated according to sex and age. Results: Male sex and age were independent prognostic factors for overall survival (OS) but not relapse-free survival (RFS). In young (⩽55 years) patients, there were no significant differences in RFS and OS between men and women. However, older (>55 years) men had a poorer OS and older women had a poorer RFS. Young female patients had a higher proportion of gastric cancer-related death than young male patients. Female sex was an independent risk factor for nodal involvement in younger patients. Conclusions: Young women with EGC should be more intensively treated and monitored than other patient groups and should not be treated by endoscopic resection. PMID:28203280

  6. 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.

  7. Lung, gastric and colorectal cancer mortality by occupation and industry among working-aged men in Japan

    PubMed Central

    Eguchi, Hisashi; Wada, Koji; Prieto-Merino, David; Smith, Derek R.

    2017-01-01

    We examined occupational and industrial differences in lung, gastric, and colorectal cancer risk among Japanese men of working age (25–64 years) using the 2010 Japanese national survey data for occupation and industry-specific death rates. Poisson regression models were used to estimate the age-adjusted incident rate ratios by lung, gastric, and colorectal cancers, with manufacturing used as the referent occupation or industry. Unemployed Japanese men and those in manufacturing had an 8–11-fold increased risk of lung, gastric and colorectal cancer. The highest mortality rates for lung and colorectal cancer by occupation were “administrative and managerial” (by occupation) and “mining” (by industry). For gastric cancer, the highest mortality rate was “agriculture” (by occupation) and “mining” (by industry). By occupation; Japanese men in service occupations, those in administrative and managerial positions, those in agriculture, forestry and fisheries, and those in professional and engineering categories had higher relative mortality risks for lung, gastric, and colorectal cancers. By industry; mining, electricity and gas, fisheries, and agriculture and forestry had the higher mortality risks for those cancers. Unemployed men had higher mortality rates than men in any occupation and industry for all three cancers. Overall, this study suggests that for Japanese men, occupations and industries may be a key social determinant of health. PMID:28230191

  8. Lung, gastric and colorectal cancer mortality by occupation and industry among working-aged men in Japan.

    PubMed

    Eguchi, Hisashi; Wada, Koji; Prieto-Merino, David; Smith, Derek R

    2017-02-23

    We examined occupational and industrial differences in lung, gastric, and colorectal cancer risk among Japanese men of working age (25-64 years) using the 2010 Japanese national survey data for occupation and industry-specific death rates. Poisson regression models were used to estimate the age-adjusted incident rate ratios by lung, gastric, and colorectal cancers, with manufacturing used as the referent occupation or industry. Unemployed Japanese men and those in manufacturing had an 8-11-fold increased risk of lung, gastric and colorectal cancer. The highest mortality rates for lung and colorectal cancer by occupation were "administrative and managerial" (by occupation) and "mining" (by industry). For gastric cancer, the highest mortality rate was "agriculture" (by occupation) and "mining" (by industry). By occupation; Japanese men in service occupations, those in administrative and managerial positions, those in agriculture, forestry and fisheries, and those in professional and engineering categories had higher relative mortality risks for lung, gastric, and colorectal cancers. By industry; mining, electricity and gas, fisheries, and agriculture and forestry had the higher mortality risks for those cancers. Unemployed men had higher mortality rates than men in any occupation and industry for all three cancers. Overall, this study suggests that for Japanese men, occupations and industries may be a key social determinant of health.

  9. Treatment of gastric cancer

    PubMed Central

    Orditura, Michele; Galizia, Gennaro; Sforza, Vincenzo; Gambardella, Valentina; Fabozzi, Alessio; Laterza, Maria Maddalena; Andreozzi, Francesca; Ventriglia, Jole; Savastano, Beatrice; Mabilia, Andrea; Lieto, Eva; Ciardiello, Fortunato; De Vita, Ferdinando

    2014-01-01

    The authors focused on the current surgical treatment of resectable gastric cancer, and significance of peri- and post-operative chemo or chemoradiation. Gastric cancer is the 4th most commonly diagnosed cancer and the second leading cause of cancer death worldwide. Surgery remains the only curative therapy, while perioperative and adjuvant chemotherapy, as well as chemoradiation, can improve outcome of resectable gastric cancer with extended lymph node dissection. More than half of radically resected gastric cancer patients relapse locally or with distant metastases, or receive the diagnosis of gastric cancer when tumor is disseminated; therefore, median survival rarely exceeds 12 mo, and 5-years survival is less than 10%. Cisplatin and fluoropyrimidine-based chemotherapy, with addition of trastuzumab in human epidermal growth factor receptor 2 positive patients, is the widely used treatment in stage IV patients fit for chemotherapy. Recent evidence supports the use of second-line chemotherapy after progression in patients with good performance status PMID:24587643

  10. Genetics of Gastric Cancer.

    PubMed

    Strand, Matthew S; Lockhart, Albert Craig; Fields, Ryan C

    2017-04-01

    Gastric cancer represents a major cause of cancer mortality worldwide despite a declining incidence. New molecular classification schemes developed from genomic and molecular analyses of gastric cancer have provided a framework for understanding this heterogenous disease, and early findings suggest these classifications will be relevant for designing and implementing new targeted therapies. The success of targeted therapy and immunotherapy in breast cancer and melanoma, respectively, has not been duplicated in gastric cancer, but trastuzumab and ramucirumab have demonstrated efficacy in select populations. New markers that predict therapeutic response are needed to improve patient selection for both targeted and immunotherapies.

  11. Gastrin and Gastric Cancer

    PubMed Central

    Waldum, Helge L.; Sagatun, Liv; Mjønes, Patricia

    2017-01-01

    Gastric cancer although occurring in reduced frequency is still an important disease, partly because of the bad prognosis when occurring in western countries. This decline in occurrence may mainly be due to the reduced prevalence of Helicobacter pylori (Hp) infection, which is the most important cause of gastric cancer. There exist many different pathological classifications of gastric carcinomas, but the most useful seems to be the one by Lauren into intestinal and diffuse types since these types seldom transform into the other and also have different epidemiology. During the nearly 30 years that have passed since the groundbreaking description of Hp as the cause of gastritis and gastric cancer, a continuous search for the mechanism by which Hp infection causes gastric cancer has been done. Interestingly, it is mainly atrophic gastritis of the oxyntic mucosa that predisposes to gastric cancer possibly by inducing hypoacidity and hypergastrinemia. There are many arguments in favor of an important role of gastrin and its target cell, the enterochromaffin-like cell, in gastric carcinogenesis. The role of gastrin in gastric carcinogenesis implies caution in the long-term treatment with inhibitors of gastric acid secretion inducing secondary hypergastrinemia, in a common disease like gastroesophageal reflux disease. PMID:28144230

  12. Surgery for gastric cancer patients of age 85 and older: Multicenter survey

    PubMed Central

    Konishi, Hirotaka; Ichikawa, Daisuke; Itoh, Hiroshi; Fukuda, Kenichiro; Kakihara, Naoki; Takemura, Manabu; Okugawa, Kaori; Uchiyama, Kiyoshi; Nakata, Masashi; Nishi, Hiroshi; Kosuga, Toshiyuki; Komatsu, Shuhei; Okamoto, Kazuma; Otsuji, Eigo

    2017-01-01

    AIM To investigate the surgical therapies for gastric cancer (GC) patients of age 85 or older in a multicenter survey. METHODS Therapeutic opportunities for elderly GC patients have expanded in conjunction with extended life expectancy. However, the number of cases encountered in a single institution is usually very small and surgical therapies for elderly GC patients have not yet been standardized completely. In the present study, a total of 134 GC patients of age 85 or older who underwent surgery in 9 related facilities were retrospectively investigated. The relationships between surgical therapies and clinicopathological or prognostic features were analyzed. RESULTS Eighty-nine of the patients (66%) presented with a comorbidity, and 26 (19% overall) presented with more than two comorbidities. Radical lymphadenectomy was performed in 59 patients (44%), and no patient received pre- or post-operative chemotherapy. Forty of the patients (30%) experienced perioperative complications, but no surgical or perioperative mortality occurred. Laparoscopic surgery was performed in only 12 of the patients (9.0%). Univariate and multivariate analyses of the 113 patients who underwent R0 or R1 resection identified the factors of pT3/4 and limited lymphadenectomy as predictive of worse prognosis (HR = 4.68, P = 0.02 and HR =2.19, P = 0.05, respectively). Non-cancer-specific death was more common in cStage I patients than in cStage II or III patients. Limited lymphadenectomy correlated with worse cancer-specific survival (P = 0.01), particularly in cStage II patients (P < 0.01). There were no relationships between limited lymphadenectomy and any comorbidities, except for cerebrovascular disease (P = 0.07). CONCLUSION Non-cancer-specific death was not negligible, particularly in cStage I, and gastrectomy with radical lymphadenectomy appears to be an effective treatment for cStage II elderly GC patients. PMID:28275301

  13. Current issues in gastric cancer epidemiology.

    PubMed

    Patru, C L; Surlin, V; Georgescu, I; Patru, Emilia

    2013-01-01

    Gastric cancer, one of the most common malignant tumors of digestive tract continues to be a major health problem by frequency, aggressiveness and low rate of cure in symptomatic stage. Although its incidence is decreasing (especially in the West), globally the gastric cancer is ranked fourth in incidence among cancers at various sites. Despite these developments, the gastric cancer mortality, overall declining globally, is high. especially in the West where even if diagnosed fewer cases of gastric cancer, TNM stages are advanced and have a poor prognosis. In contrast, in Japan, where the incidence is still high, the percentage of cases diagnosed at the stage of "early gastric cancer" has greatly increased, thus improving prognosis. Gastric neoplasia affects more men, age range 50-70 years, disadvantaged social classes and black race. In Romania the gastric cancer incidence is increasing over recent years, presenting variations across the country being more common in men compared with women, reaching a peak of incidence around age 60. Gastric cancer mortality in the world places Romania among the countries with average mortality. Gastric cancer prognosis remains extremely reserved, in close correlation with tumor stage at diagnosis, surgical treatment being the only possibility to provide improved survival, especially in the early stages. Improvement of survival rate in recent years is due to increased gastric resectability result of an earlier diagnosis, a more complex treatment and a closer monitoring of the population at risk.

  14. Helicobacter pylori and early gastric cancer.

    PubMed Central

    Craanen, M E; Blok, P; Dekker, W; Tytgat, G N

    1994-01-01

    The relation between Helicobacter pylori, intestinal metaplasia, and early gastric cancer was studied by examining gastrectomy specimens from 31 intestinal type and 22 diffuse type carcinomas. A total of 298 patients with antral gastritis were used as controls. Atrophic changes and intestinal metaplasia were significantly more common in intestinal type early gastric cancer compared with diffuse type early gastric cancer (p < 0.05 and p < 0.001, respectively). H pylori was found in 61.3% of intestinal type early gastric cancer and in 54.5% of diffuse type early gastric cancer (NS). The age adjusted prevalence of intestinal metaplasia in the patients with antral gastritis was higher in H pylori positive patients in all age groups studied. Comparing gastritis patients with patients with intestinal type early gastric cancer showed the age adjusted prevalence of intestinal metaplasia to be significantly higher in the patients with early gastric cancer in all age groups studied. In conclusion, H pylori is associated with both types of early gastric carcinoma. Intestinal metaplasia formation seems to be a multifactorial process in which H pylori may play a part. These findings suggest that gastric cancer may be included in the spectrum of H pylori associated diseases, although many questions about causality remain to be answered. PMID:7959189

  15. Clinical Characteristics and Outcomes of Gastric Cancer Patients Aged over 80 Years: A Retrospective Case-Control Study

    PubMed Central

    Jung, Hwoon-Yong; Lee, Jeong Hoon; Jung, Kee Wook; Kim, Do Hoon; Choi, Kee Don; Song, Ho June; Lee, Gin Hyug; Kim, Jin-Ho; Han, Seungbong

    2016-01-01

    Background and Aims The average human life expectancy is increasing worldwide, thus the proportion of elderly gastric cancer patients is also increasing. In this case-control study, we investigated the clinical and oncologic outcomes of gastric cancer in patients over 80 years old. Methods From January 2004 to December 2010, 291 patients aged over 80 years old (case group) were diagnosed and treated with gastric cancer at Asan Medical Center, Seoul, Korea. From the same period, 291 patients aged 18 to 80 years old were selected as the control group. The clinical findings and clinical outcomes of gastric cancer were retrospectively reviewed and compared between the two groups. Results There were significant differences in the overall 5-year survival rate between the case and control groups (30.9% vs. 73.8%, respectively; P<0.001). In patients who received the curative treatment, overall 3- and 5-year survival rates showed 74.3% and 57.9% in case group and 91.6% and 86.5% in the control group. When analysis was confined to resectable elderly patients with a favorable performance, the curative resection group showed significantly better overall 3- and 5-year survival rates than the conservative treatment group (73.7% and 58.8% vs. 29.8% and 0%, respectively). Conclusions Although elderly gastric cancer patients show an advanced stage at diagnosis and poor prognosis compared with non-elderly patients, elderly patients with good performance could benefit from curative resection. Thus, the clinical decision whether to undergo curative resection or conservative management should be made on an individualized basis. PMID:27942044

  16. 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

  17. Immunotherapy in gastric cancer.

    PubMed

    Matsueda, Satoko; Graham, David Y

    2014-02-21

    Gastric cancer is the second most common of cancer-related deaths worldwide. In the majority of cases gastric cancer is advanced at diagnosis and although medical and surgical treatments have improved, survival rates remain poor. Cancer immunotherapy has emerged as a powerful and promising clinical approach for treatment of cancer and has shown major success in breast cancer, prostate cancer and melanoma. Here, we provide an overview of concepts of modern cancer immunotherapy including the theory, current approaches, remaining hurdles to be overcome, and the future prospect of cancer immunotherapy in the treatment of gastric cancer. Adaptive cell therapies, cancer vaccines, gene therapies, monoclonal antibody therapies have all been used with some initial successes in gastric cancer. However, to date the results in gastric cancer have been disappointing as current approaches often do not stimulate immunity efficiently allowing tumors continue to grow despite the presence of a measurable immune response. Here, we discuss the identification of targets for immunotherapy and the role of biomarkers in prospectively identifying appropriate subjects or immunotherapy. We also discuss the molecular mechanisms by which tumor cells escape host immunosurveillance and produce an immunosuppressive tumor microenvironment. We show how advances have provided tools for overcoming the mechanisms of immunosuppression including the use of monoclonal antibodies to block negative regulators normally expressed on the surface of T cells which limit activation and proliferation of cytotoxic T cells. Immunotherapy has greatly improved and is becoming an important factor in such fields as medical care and welfare for human being. Progress has been rapid ensuring that the future of immunotherapy for gastric cancer is bright.

  18. 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

  19. Familial Gastric Cancers

    PubMed Central

    Setia, Namrata; Clark, Jeffrey W.; Duda, Dan G.; Hong, Theodore S.; Kwak, Eunice L.; Mullen, John T.

    2015-01-01

    Although the majority of gastric carcinomas are sporadic, approximately 10% show familial aggregation, and a hereditary cause is determined in 1%–3% cases. Of these, hereditary diffuse gastric cancer is the most recognized predisposition syndrome. Although rare, the less commonly known syndromes also confer a markedly increased risk for development of gastric cancer. Identification and characterization of these syndromes require a multidisciplinary effort involving oncologists, surgeons, genetic counselors, biologists, and pathologists. This article reviews the molecular genetics, clinical and pathologic features, surveillance guidelines, and preventive measures of common and less common hereditary gastric cancer predisposition syndromes. Implications for Practice: Although the majority of gastric adenocarcinomas are sporadic with many of those related to chronic Helicobacter pylori infection, approximately 10% of the cases show familial aggregation, and a specific hereditary cause is determined in 1%–3% cases. This review describes the molecular genetics, clinical and pathologic features, surveillance guidelines, and preventive measures of common and less common hereditary gastric cancer predisposition syndromes. Ultimately, a better understanding of the biology of these conditions should allow early identification and intervention as part of a multidisciplinary approach involving oncologists, surgeons, genetic counselors, and pathologists. PMID:26424758

  20. Nutrition and gastric cancer in Turkey.

    PubMed

    Yalçin, Suayib

    2009-01-01

    Gastric cancer remains to be one of leading causes of cancer deaths despite worldwide decreasing incidence. In Turkey gastric cancer incidence is 9.6/100,000 in men and 5.7/100,000 in females. Gastric cancer is also one of the leading causes of cancer deaths in Turkey with a crude death rate of 5.84/100,000 in men, 3.7/100,000 in women. The mean age of patients diagnosed with gastric cancer is 56 years in Turkey. The relatively high rate of gastric cancer in Turkey is mainly due to dietary factors. The traditional food preservation such as salt curing or smoking and lack of refrigeration of food play a significant role in gastric cancer development in the country. There are etiological and epidemiological differences among geographical regions in Turkey. Gastric cancer is seen much more often in the central, northeastern, and eastern part of Turkey. Increased HP pylori infection is also another important reason for increased incidence of gastric cancer in some parts of the country.

  1. Gastric metastasis of bilateral breast cancer

    PubMed Central

    Belaïd, Asma; Mghirbi, Fahmi; Béhi, Khalil; Doghri, Raoudha; Benna, Farouk

    2017-01-01

    Breast cancer is the most common malignancy in women. The most frequent metastatic sites are lung, bone, liver and brain. On the other hand, gastric metastases are rare. Synchronous bilateral breast cancer (SBBC) occurs rarely. Lobular carcinoma is the histological type most often associated with bilateral breast carcinomas and gastric metastases. We made a retrospective study including four patients followed in the Salah Azaiez Institute, for a bilateral breast cancer with gastric metastases. We analyzed the epidemiological, anatomoclinical and therapeutic particularities of this rare entity. Symptoms were unspecific. The diagnosis of gastric metastasis of the SBBC was confirmed by a histopathological examination of an endoscopic biopsy. The median age was 46.2 years (range, 36–51 years) and the median time until the gastric involvement was 19 months (range, 0–41 months). None of patients had a surgical treatment for the gastric location. All Patients received at least one line of chemotherapy and radiotherapy. Median survival following the detection of gastric involvement was 22 months (range, 1–56 months). Gastric metastases from breast cancer are rare and frequently associated with other distant metastasis. Symptoms are unspecific and endoscopy may not be contributive. Therefore, gastric involvement is underestimated. Lobular infiltrating carcinoma (LIC) is the most histological type incriminated in its occurrence. The supply of immunohistochemistry is crucial to distinguish between primary or metastatic gastric cancer. PMID:28280631

  2. Endoscopic submucosal dissection for early gastric cancer in very elderly patients age 85 or older

    PubMed Central

    Watanabe, Ko; Hikichi, Takuto; Nakamura, Jun; Takagi, Tadayuki; Suzuki, Rei; Sugimoto, Mitsuru; Waragai, Yuichi; Kikuchi, Hitomi; Konno, Naoki; Asama, Hiroyuki; Takasumi, Mika; Obara, Katsutoshi; Ohira, Hiromasa

    2017-01-01

    Background and study aims The safety and efficacy of endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) in very elderly patients remains unclear. The aim of this study was to evaluate the safety and efficacy of ESD for EGC in patients age 85 years and older. Patients and methods Patients who underwent ESD for EGC between September 2003 and April 2015 were divided into 3 groups: the very elderly (≥ 85 years; 43 patients), the elderly (65 – 84 years; 511 patients), and the non-elderly ( ≤ 64 years; 161 patients). Adverse events (AEs) were used as the primary endpoint to assess the safety of ESD, and the ESD treatment outcomes (i. e., en bloc resection rate, complete en bloc resection rate, and curative resection rate) and the overall survival rate after ESD were the secondary endpoints. These parameters were retrospectively evaluated in the 3 groups. Results There were no significant differences in AEs (non-elderly, elderly, and very elderly: 7.3, 9.5, and 12.5 %, respectively, P = 0.491) or in the en bloc resection and complete en bloc resection rates among the three groups. However, there was a significant difference in the curative resection rates (non-elderly, elderly, and very elderly: 91.5, 84.1, and 77.1 %, respectively, P = 0.014). Regarding overall survival, there was a significant difference among the three groups (1-, 5-, and 10-year overall survival rates: non-elderly: 98.6, 90.2, and 74.7 %; elderly: 97.2, 86.2, and 61.9 %; and very elderly: 92.7, 66.8, and 34.4 %, respectively, P = 0.001). Moreover, the overall survival rate in the very elderly patients with cardiovascular disease was significantly lower than that in the very elderly patients without cardiovascular disease (P < 0.001). Conclusions ESD is an acceptable treatment for EGC in patients 85 years of age or older in terms of safety. However, the overall survival after ESD in the very elderly patients with cardiovascular

  3. 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

  4. Gastric cancer: basic aspects.

    PubMed

    Resende, Carlos; Thiel, Alexandra; Machado, José C; Ristimäki, Ari

    2011-09-01

    Gastric cancer (GC) is a world health burden, ranging as the second cause of cancer death worldwide. Etiologically, GC arises not only from the combined effects of environmental factors and susceptible genetic variants but also from the accumulation of genetic and epigenetic alterations. In the last years, molecular oncobiology studies brought to light a number of genes that are implicated in gastric carcinogenesis. This review is intended to focus on the recently described basic aspects that play key roles in the process of gastric carcinogenesis. Genetic variants of the genes IL-10, IL-17, MUC1, MUC6, DNMT3B, SMAD4, and SERPINE1 have been reported to modify the risk of developing GC. Several genes have been newly associated with gastric carcinogenesis, both through oncogenic activation (GSK3β, CD133, DSC2, P-Cadherin, CDH17, CD168, CD44, metalloproteinases MMP7 and MMP11, and a subset of miRNAs) and through tumor suppressor gene inactivation mechanisms (TFF1, PDX1, BCL2L10, XRCC, psiTPTE-HERV, HAI-2, GRIK2, and RUNX3). It also addressed the role of the inflammatory mediator cyclooxygenase-2 (COX-2) in the process of gastric carcinogenesis and its importance as a potential molecular target for therapy.

  5. Molecular biology of gastric cancer.

    PubMed

    Cervantes, A; Rodríguez Braun, E; Pérez Fidalgo, A; Chirivella González, I

    2007-04-01

    Despite its decreasing incidence overall, gastric cancer is still a challenging disease. Therapy is based mainly upon surgical resection when the tumour remains localised in the stomach. Conventional chemotherapy may play a role in treating micrometastatic disease and is effective as palliative therapy for recurrent or advanced disease. However, the knowledge of molecular pathways implicated in gastric cancer pathogenesis is still in its infancy and the contribution of molecular biology to the development of new targeted therapies in gastric cancer is far behind other more common cancers such as breast, colon or lung. This review will focus first on the difference of two well defined types of gastric cancer: intestinal and diffuse. A discussion of the cell of origin of gastric cancer with some intriguing data implicating bone marrow derived cells will follow, and a comprehensive review of different genetic alterations detected in gastric cancer, underlining those that may have clinical, therapeutic or prognostic implications.

  6. 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

  7. Prevalence and Risk Factors of Gastric Adenoma and Gastric Cancer in Colorectal Cancer Patients

    PubMed Central

    Jeong, Hyun Yong

    2016-01-01

    Background/Aims. To evaluate the incidence of gastric adenoma and gastric cancer in colorectal cancer patients, as well as the clinicopathological features that affect their incidence. Methods. Among patients who underwent surgery after being diagnosed with colorectal cancer between January 2004 and December 2013 at Chungnam National University Hospital, 142 patients who underwent follow-up upper gastrointestinal endoscopy were assigned to the patient group. The control group included 426 subjects randomly selected. The patient group was subdivided into two: one that developed gastric adenoma or cancer and one that did not. Clinicopathological characteristics were compared between these groups. Results. In total, 35 (24.6%) colorectal cancer patients developed a gastric adenoma or gastric cancer, which was higher than the number in the control group (20 [4.7%] patients; p < 0.001). Age, alcohol history, and differentiation of colorectal cancer were associated with higher risks of gastric adenoma or gastric cancer, with odds ratios of 1.062, 6.506, and 5.901, respectively. Conclusions. In colorectal cancer patients, screening with upper gastrointestinal endoscopy is important, even if no lesions are noted in the upper gastrointestinal tract at colorectal cancer diagnosis. Endoscopic screening is particularly important with increasing age, history of alcohol consumption, and poor cancer differentiation. PMID:28105047

  8. Usefulness of Photodynamic Diagnosis and Therapy using Talaporfin Sodium for an Advanced-aged Patient with Inoperable Gastric Cancer (a secondary publication)

    PubMed Central

    Oinuma, Takeshi

    2014-01-01

    Background and aims: In Japan the rise in the average life expectancy has caused an increase in the proportion of the population who are classed as geriatric. Accordingly, the number of elderly people being treated for cancer is increasing concomitantly. However, with the increase in age, the numbers of prior complications also increase. This is especially so in the advanced-aged patients, defined in Japan as those over the age of 85. Such complications may be too high risk for radical surgery and a less invasive treatment is warranted. Photodynamic therapy (PDT) is a noninvasive treatment approved by the Japanese National Health Insurance for the treatment of early stage superficial type esophageal and gastric cancers, early stage uterine cervical cancers and dysplasia, and early and advanced lung cancer. We report herein on the efficacy of palliative PDT using talaporfin sodium (Laserphyrin®) for a case of inoperable gastric cancer. Material and methods: The patient was an 87-year-old-man, a diabetic with histories of diabetic nephropathy, cerebral infarction and myocardial infarction. This patient was first diagnosed as having gastric cancer in 2007 but surgery and chemotherapy were contraindicated due to his poor physical status and poor renal function, respectively, owing to the anticipated side effects. The patient was referred to our institution after hearing of PDT in 2009. He was treated with 1 course of porfimer sodium PDT and 3 courses of talaporfin sodium PDT with photodynamic diagnosis (PDD) during the period from September, 2009 to June, 2011. Results: The massive gastric cancer located in the cardia was successfully treated with 4 PDT sessions without any serious complications; therefore the patient was able to orally ingest food until his death due to natural causes other than the cancer, in October, 2011. Conclusion: Talaporfin sodium PDT is safe and effective treatment for advanced-aged patients suffering from inoperable gastric cancer. PMID

  9. Gene methylation in gastric cancer.

    PubMed

    Qu, Yiping; Dang, Siwen; Hou, Peng

    2013-09-23

    Gastric cancer is one of the most common malignancies and remains the second leading cause of cancer-related death worldwide. Over 70% of new cases and deaths occur in developing countries. In the early years of the molecular biology revolution, cancer research mainly focuses on genetic alterations, including gastric cancer. Epigenetic mechanisms are essential for normal development and maintenance of tissue-specific gene expression patterns in mammals. Disruption of epigenetic processes can lead to altered gene function and malignant cellular transformation. Recent advancements in the rapidly evolving field of cancer epigenetics have shown extensive reprogramming of every component of the epigenetic machinery in cancer, including DNA methylation, histone modifications, nucleosome positioning, noncoding RNAs, and microRNAs. Aberrant DNA methylation in the promoter regions of gene, which leads to inactivation of tumor suppressor and other cancer-related genes in cancer cells, is the most well-defined epigenetic hallmark in gastric cancer. The advantages of gene methylation as a target for detection and diagnosis of cancer in biopsy specimens and non-invasive body fluids such as serum and gastric washes have led to many studies of application in gastric cancer. This review focuses on the most common and important phenomenon of epigenetics, DNA methylation, in gastric cancer and illustrates the impact epigenetics has had on this field.

  10. 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.

  11. Inflammation, atrophy, and gastric cancer

    PubMed Central

    Fox, James G.; Wang, Timothy C.

    2006-01-01

    The association between chronic inflammation and cancer is now well established. This association has recently received renewed interest with the recognition that microbial pathogens can be responsible for the chronic inflammation observed in many cancers, particularly those originating in the gastrointestinal system. A prime example is Helicobacter pylori, which infects 50% of the world’s population and is now known to be responsible for inducing chronic gastric inflammation that progresses to atrophy, metaplasia, dysplasia, and gastric cancer. This Review provides an overview of recent progress in elucidating the bacterial properties responsible for colonization of the stomach, persistence in the stomach, and triggering of inflammation, as well as the host factors that have a role in determining whether gastritis progresses to gastric cancer. We also discuss how the increased understanding of the relationship between inflammation and gastric cancer still leaves many questions unanswered regarding recommendations for prevention and treatment. PMID:17200707

  12. Acetaldehyde and gastric cancer.

    PubMed

    Salaspuro, Mikko

    2011-04-01

    Aldehyde dehydrogenase (ALDH2) and alcohol dehydrogenase (ADH) gene polymorphisms associating with enhanced acetaldehyde exposure and markedly increased cancer risk in alcohol drinkers provide undisputable evidence for acetaldehyde being a local carcinogen not only in esophageal but also in gastric cancer. Accordingly, acetaldehyde associated with alcoholic beverages has recently been classified as a Group 1 carcinogen to humans. Microbes are responsible for the bulk of acetaldehyde production from ethanol both in saliva and Helicobacter pylori-infected and achlorhydric stomach. Acetaldehyde is the most abundant carcinogen in tobacco smoke and it readily dissolves into saliva during smoking. Many foodstuffs and 'non-alcoholic' beverages are important but unrecognized sources of local acetaldehyde exposure. The cumulative cancer risk associated with increasing acetaldehyde exposure suggests the need for worldwide screening of the acetaldehyde levels of alcoholic beverages and as well of the ethanol and acetaldehyde of food produced by fermentation. The generally regarded as safe status of acetaldehyde should be re-evaluated. The as low as reasonably achievable principle should be applied to the acetaldehyde of alcoholic and non-alcoholic beverages and food. Risk groups with ADH-and ALDH2 gene polymorphisms, H. pylori infection or achlorhydric atrophic gastritis, or both, should be screened and educated in this health issue. L-cysteine formulations binding carcinogenic acetaldehyde locally in the stomach provide new means for intervention studies.

  13. DBGC: A Database of Human Gastric Cancer

    PubMed Central

    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

  14. 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.

  15. Gastric cancer in Italy.

    PubMed

    Cipriani, F; Buiatti, E; Palli, D

    1991-01-01

    Although Gastric Cancer (GC) death rates are decreasing worldwide, in high risk areas GC is still a major public health problem. Italy is one of the European countries with the highest mortality rates for GC (males: 17.3; females: 8.2 x 100,000 inhabitants in 1987) which represents the third cause of death due to cancer in 1987, accounting for over 14,000 deaths per year (10% of cancer deaths). Reasons for the geographic variability in GC occurrence within the country are reviewed, discussing the results of two recent analytical epidemiological studies carried out in Italy. These large case-control studies focused on dietary factors, involving high and low-risk areas for GC (Florence, Siena, Forlì, Imola, Cremona, Genoa, Cagliari, and Milan). Low socio-economic status, family history of GC, residence in rural areas were associated to GC risk, while migration from southern areas and body mass index were inversely related to GC. Consumption of traditional soups, meat, salted and dried fish, cold cuts and seasoned cheeses, as well as the intake of animal proteins and nitrites were related to an increased GC risk. On the contrary consumption of fresh fruit, citrus fruit, raw vegetables, spices, garlic and olive oil, and vitamin C, E and beta-carotene intake were found to be protective factors. Among diet-related factors, preference for salty foods and frequent broiling were positively related to GC, while the longstanding availbility of a refrigerator or freezer and the habits of consuming frozen foods were associated with decreased GC risk. These results are discussed in detail, considering the main hypotheses on GC carcinogenesis.

  16. 64Cu DOTA-Trastuzumab PET/CT in Studying Patients With Gastric Cancer

    ClinicalTrials.gov

    2017-03-24

    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

  17. 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

  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

    2016-12-30

    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. Overdiagnosis of gastric cancer by endoscopic screening

    PubMed Central

    Hamashima, Chisato

    2017-01-01

    Gastric cancer screening using endoscopy has recently spread in Eastern Asian countries showing increasing evidence of its effectiveness. However, despite the benefits of endoscopic screening for gastric cancer, its major harms include infection, complications, false-negative results, false-positive results, and overdiagnosis. The most serious harm of endoscopic screening is overdiagnosis and this can occur in any cancer screening programs. Overdiagnosis is defined as the detection of cancers that would never have been found if there is no cancer screening. Overdiagnosis has been estimated from randomized controlled trials, observational studies, and modeling. It can be calculated on the basis of a comparison of the incidence of cancer between screened and unscreened individuals after the follow-up. Although the estimation method for overdiagnosis has not yet been standardized, estimation of overdiagnosis is needed in endoscopic screening for gastric cancer. To minimize overdiagnosis, the target age group and screening interval should be appropriately defined. Moreover, the balance of benefits and harms must be carefully considered to effectively introduce endoscopic screening in communities. Further research regarding overdiagnosis is warranted when evaluating the effectiveness of endoscopic screening. PMID:28250897

  20. Overdiagnosis of gastric cancer by endoscopic screening.

    PubMed

    Hamashima, Chisato

    2017-02-16

    Gastric cancer screening using endoscopy has recently spread in Eastern Asian countries showing increasing evidence of its effectiveness. However, despite the benefits of endoscopic screening for gastric cancer, its major harms include infection, complications, false-negative results, false-positive results, and overdiagnosis. The most serious harm of endoscopic screening is overdiagnosis and this can occur in any cancer screening programs. Overdiagnosis is defined as the detection of cancers that would never have been found if there is no cancer screening. Overdiagnosis has been estimated from randomized controlled trials, observational studies, and modeling. It can be calculated on the basis of a comparison of the incidence of cancer between screened and unscreened individuals after the follow-up. Although the estimation method for overdiagnosis has not yet been standardized, estimation of overdiagnosis is needed in endoscopic screening for gastric cancer. To minimize overdiagnosis, the target age group and screening interval should be appropriately defined. Moreover, the balance of benefits and harms must be carefully considered to effectively introduce endoscopic screening in communities. Further research regarding overdiagnosis is warranted when evaluating the effectiveness of endoscopic screening.

  1. 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

  2. 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

  3. Familial gastric cancer - clinical management.

    PubMed

    Fitzgerald, Rebecca C; Caldas, Carlos

    2006-01-01

    The clinical management of familial gastric cancer is the same as that for sporadic gastric cancer at the current time. As the causative mutations for these cases are identified this should lead to the development of specific treatments which target the molecular abnormality. The only germline mutations identified so far occur within the E-cadherin gene (CDHI) and they account for approximately 30% of familial gastric cancer cases. When index patients fulfilling the clinical criteria for hereditary diffuse gastric cancer syndrome have a CDHI mutation identified then genetic testing of asymptomatic relatives should be considered. The clinical sequelae of testing positive for such a mutation are profound and therefore it is essential that counselling is given prior to genetic testing. The management options are surveillance endoscopy and prophylactic gastrectomy. In this chapter the practicalities of genetic testing are discussed as well as the pros and cons of the two management options. It is essential that experience of these rare families is pooled so that surveillance and treatment can be optimised in the future.

  4. Pathogenetic mechanisms in gastric cancer

    PubMed Central

    Shi, Jing; Qu, Yi-Ping; Hou, Peng

    2014-01-01

    Gastric cancer (GC) is a major public health issue as the fourth most common cancer and the second leading cause of cancer-related death. Recent advances have improved our understanding of its molecular pathogenesis, as best exemplified by elucidating the fundamental role of several major signaling pathways and related molecular derangements. Central to these mechanisms are the genetic and epigenetic alterations in these signaling pathways, such as gene mutations, copy number variants, aberrant gene methylation and histone modification, nucleosome positioning, and microRNAs. Some of these genetic/epigenetic alterations represent effective diagnostic and prognostic biomarkers and therapeutic targets for GC. This information has now opened unprecedented opportunities for better understanding of the molecular mechanisms of gastric carcinogenesis and the development of novel therapeutic strategies for this cancer. The pathogenetic mechanisms of GC are the focus of this review. PMID:25320518

  5. 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

  6. Non-coding RNAs and gastric cancer

    PubMed Central

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

    2014-01-01

    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

  7. Stomach (Gastric) Cancer Screening

    MedlinePlus

    ... in which malignant (cancer) cells form in the lining of the stomach. The stomach is a J- ... outermost) layer. Stomach cancer begins in the cells lining the mucosal layer and spreads through the outer ...

  8. 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.

  9. 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.

  10. Stomach (Gastric) Cancer Prevention

    MedlinePlus

    ... Overview History of NCI Contributing to Cancer Research Senior Leadership Director Previous Directors NCI Organization Divisions, Offices & Centers Advisory Boards & Groups Budget & Appropriations Current Year Budget Annual Plan & Budget ...

  11. 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.

  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. PMID:27672425

  13. Gastric cancer stem cells: A novel therapeutic target

    PubMed Central

    Singh, Shree Ram

    2013-01-01

    Gastric cancer remains one of the leading causes of global cancer mortality. Multipotent gastric stem cells have been identified in both mouse and human stomachs, and they play an essential role in the self-renewal and homeostasis of gastric mucosa. There are several environmental and genetic factors known to promote gastric cancer. In recent years, numerous in vitro and in vivo studies suggest that gastric cancer may originate from normal stem cells or bone marrow–derived mesenchymal cells, and that gastric tumors contain cancer stem cells. Cancer stem cells are believed to share a common microenvironment with normal niche, which play an important role in gastric cancer and tumor growth. This mini-review presents a brief overview of the recent developments in gastric cancer stem cell research. The knowledge gained by studying cancer stem cells in gastric mucosa will support the development of novel therapeutic strategies for gastric cancer. PMID:23583679

  14. Does remnant gastric cancer really differ from primary gastric cancer? A systematic review of the literature by the Task Force of Japanese Gastric Cancer Association.

    PubMed

    Shimada, Hideaki; Fukagawa, Takeo; Haga, Yoshio; Oba, Koji

    2016-04-01

    Remnant gastric cancer, most frequently defined as cancer detected in the remnant stomach after distal gastrectomy for benign disease and those cases after surgery of gastric cancer at least 5 years after the primary surgery, is often reported as a tumor with poor prognosis. The Task Force of Japanese Gastric Cancer Association for Research Promotion evaluated the clinical impact of remnant gastric cancer by systematically reviewing publications focusing on molecular carcinogenesis, lymph node status, patient survival, and surgical complications. A systematic literature search was performed using PubMed/MEDLINE with the keywords "remnant," "stomach," and "cancer," revealing 1154 relevant reports published up to the end of December 2014. The mean interval between the initial surgery and the diagnosis of remnant gastric cancer ranged from 10 to 30 years. The incidence of lymph node metastases at the splenic hilum for remnant gastric cancer is not significantly higher than that for primary proximal gastric cancer. Lymph node involvement in the jejunal mesentery is a phenomenon peculiar to remnant gastric cancer after Billroth II reconstruction. Prognosis and postoperative morbidity and mortality rates seem to be comparable to those for primary proximal gastric cancer. The crude 5-year mortality for remnant gastric cancer was 1.08 times higher than that for primary proximal gastric cancer, but this difference was not statistically significant. In conclusion, although no prospective cohort study has yet evaluated the clinical significance of remnant gastric cancer, our literature review suggests that remnant gastric cancer does not adversely affect patient prognosis and postoperative course.

  15. 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

  16. Gastric cancer and related epigenetic alterations

    PubMed Central

    Patel, Trupti N; Roy, Soumyadipta; Ravi, Revathi

    2017-01-01

    Gastric cancer, a malignant and highly proliferative condition, has significantly affected a large population around the globe and is known to be caused by various factors including genetic, epigenetic, and environmental influences. Though the global trend of these cancers is declining, an increase in its frequency is still a threat because of changing lifestyles and dietary habits. However, genetic and epigenetic alterations related to gastric cancers also have an equivalent contribution towards carcinogenic development. DNA methylation is one of the major forms of epigenetic modification which plays a significant role in gastric carcinogenesis. Methylation leads to inactivation of some of the most important genes like DNA repair genes, cell cycle regulators, apoptotic genes, transcriptional regulators, and signalling pathway regulators; which subsequently cause uncontrolled proliferation of cells. Mutations in these genes can be used as suitable prognostic markers for early diagnosis of the disease, since late diagnosis of gastric cancers has a huge negative impact on overall patient survival. In this review, we focus on the important epigenetic mutations that contribute to the development of gastric cancer and the molecular pathogenesis underlying each of them. Methylation, acetylation, and histone modifications play an integral role in the onset of genomic instability, one of the many contributory factors to gastric cancer. This article also covers the constraints of incomplete knowledge of epigenetic factors influencing gastric cancer, thus throwing light on our understanding of the disease. PMID:28144288

  17. Diabetes and gastric cancer: the potential links.

    PubMed

    Tseng, Chin-Hsiao; Tseng, Farn-Hsuan

    2014-02-21

    This article reviews the epidemiological evidence linking diabetes and gastric cancer and discusses some of the potential mechanisms, confounders and biases in the evaluation of such an association. Findings from four meta-analyses published from 2011 to 2013 suggest a positive link, which may be more remarkable in females and in the Asian populations. Putative mechanisms may involve shared risk factors, hyperglycemia, Helicobacter pylori (H. pylori) infection, high salt intake, medications and comorbidities. Diabetes may increase the risk of gastric cancer through shared risk factors including obesity, insulin resistance, hyperinsulinemia and smoking. Hyperglycemia, even before the clinical diagnosis of diabetes, may predict gastric cancer in some epidemiological studies, which is supported by in vitro, and in vivo studies. Patients with diabetes may also have a higher risk of gastric cancer through the higher infection rate, lower eradication rate and higher reinfection rate of H. pylori. High salt intake can act synergistically with H. pylori infection in the induction of gastric cancer. Whether a higher risk of gastric cancer in patients with diabetes may be ascribed to a higher intake of salt due to the loss of taste sensation awaits further investigation. The use of medications such as insulin, metformin, sulfonylureas, aspirin, statins and antibiotics may also influence the risk of gastric cancer, but most of them have not been extensively studied. Comorbidities may affect the development of gastric cancer through the use of medications and changes in lifestyle, dietary intake, and the metabolism of drugs. Finally, a potential detection bias related to gastrointestinal symptoms more commonly seen in patients with diabetes and with multiple comorbidities should be pointed out. Taking into account the inconsistent findings and the potential confounders and detection bias in previous epidemiological studies, it is expected that there are still more to be

  18. 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.

  19. Nutrition and Gastric Cancer Risk: An Update

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Data from epidemiologic, experimental, and animal studies indicate that diet plays an important role in the etiology of gastric cancer. High intake of fresh fruit and vegetable, lycopene and lycopene-containing food products, and potentially vitamin C and selenium may reduce the risk for gastric can...

  20. Serum biomarker screening for the diagnosis of early gastric cancer using SELDI-TOF-MS.

    PubMed

    Li, Ping; Zhang, Dianliang; Guo, Chunbao

    2012-06-01

    In this study, we performed a proteomic analysis of sera from stage I gastric cancer patients using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) and established a diagnostic model for the early diagnosis of stage I gastric cancer. Serum samples from 169 gastric cancer patients and 83 age- and gender-matched healthy individuals were analyzed by SELDI-TOF-MS ProteinChip array technology. The SELDI-TOF-MS spectral data were analyzed using the Biomarker Wizard™ and Biomarker Patterns™ software to find differential proteins and develop a classification tree for gastric cancer. A total of 34 mass peaks were identified. Six peaks at a mass-to-charge ratio (m/z) of 2873, 3163, 4526, 5762, 6121 and 7778 were used to construct the diagnostic model. The model effectively distinguished gastric cancer samples from control samples, achieving a sensitivity and specificity of 93.49 and 91.57%, respectively. In addition, we identified 3 of the 6 protein peaks at 2873, 6121 and 7778 m/z, which distinguished between stage I and stage II/III/IV gastric cancer. The model had an accuracy of 88.89% for the identification of stage I gastric cancer. In conclusion, the diagnostic model for the detection of serum proteins by SELDI-TOF-MS ProteinChip array technology correctly distinguishes gastric cancer from healthy samples, and has the ability to screen and distinguish between early gastric cancer from advanced gastric cancer.

  1. Dietary flavonoids and gastric cancer risk in a Korean population.

    PubMed

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

    2014-11-10

    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.

  2. 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.

  3. Translating gastric cancer genomics into targeted therapies.

    PubMed

    Ang, Yvonne L E; Yong, Wei Peng; Tan, Patrick

    2016-04-01

    Gastric cancer is a common disease with limited treatment options and a poor prognosis. Many gastric cancers harbour potentially actionable targets, including over-expression and mutations in tyrosine kinase pathways. Agents have been developed against these targets with varying success- in particular, the use of trastuzumab in HER2-overexpressing gastric cancers has resulted in overall survival benefits. Gastric cancers also have high levels of somatic mutations, making them candidates for immunotherapy; early work in this field has been promising. Recent advances in whole genome and multi-platform sequencing have driven the development of molecular classification systems, which may in turn guide the selection of patients for targeted treatment. Moving forward, challenges will include the development of appropriate biomarkers to predict responses to targeted therapy, and the application of new molecular classifications into trial development and clinical practice.

  4. Gastric juice miR-129 as a potential biomarker for screening gastric cancer.

    PubMed

    Yu, Xing; Luo, Lin; Wu, Yibo; Yu, Xiuchong; Liu, Yang; Yu, Xuelin; Zhao, Xiaoyan; Zhang, Xinjun; Cui, Long; Ye, Guoliang; Le, Yanping; Guo, Junming

    2013-03-01

    MicroRNAs (miRNAs) play crucial roles during the occurrence and development of gastric cancer. Conventional serological tests for screening gastric cancer have limits on sensitivity and specificity. Several miRNAs in peripheral blood have been used as biomarkers of gastric cancer. However, most of these miRNAs are shared by several types of cancer. Thanks to the tissue specificity of gastric juice, here we examined the feasibility of using gastric juice miR-129-1/2, which are aberrantly expressed in gastric cancer, to screen gastric cancer. Total of 141 gastric juices samples from gastric cancer, gastric ulcer, atrophic gastritis, and minimal gastritis patients or subjects with normal mucosa were collected by gastroscopy. The gastric juice miR-129-1/2 levels were detected by quantitative reverse transcription-polymerase chain reaction. A receiver operating characteristic (ROC) curve was constructed for differentiating patients with gastric cancer from patients with benign gastric diseases. We showed that, compared with patients with benign gastric diseases, patients with gastric cancer had significantly lower levels of gastric juice miR-129-1-3p and miR-129-2-3p. The areas under ROC curve (AUC) were 0.639 and 0.651 for miR-129-1-3p and miR-129-2-3p, respectively. Using the parallel combination test, the AUC was up to 0.656. In summary, our results suggest that gastric juice miR-129-1-3p and miR-129-2-3p are potential biomarkers for the screening gastric cancer, and the detection of gastric juice miRNAs is a convenient non-invasion method for the diagnosis of gastric cancer.

  5. 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.

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

    PubMed

    Wroblewski, Lydia E; Peek, Richard M

    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.

  7. 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

  8. 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

  9. Considerations about gastric cancer proteomics.

    PubMed

    Carvalho, Carlos Eduardo; McCormick, Thaís Messias; Carvalho, Paulo Costa; Fischer, Juliana DE Saldanha DA Gama; Aquino, Priscila Ferreira DE; Bravo, Guilherme Pinto; Carvalho, Maria DA Glória DA Costa

    2016-01-01

    The frequency of molecular studies aimed to analyze promoter methylation of tumor suppressor genes and global proteomics in gastric carcinogenesis is increasing. Nonetheless, only a few considered the different types of stomach cells, the tumor location and the influence of Helicobacter pylori and Epstein Barr virus infection (EBV). Molecular differences relating to anatomical and histological tumor areas were also recently described. The authors propose a molecular classification of gastric cancer, dividing it into four subtypes: tumors positive for EBV; microsatellite unstable tumors; genomically stable tumors and tumors with chromosomal instability. RESUMO A frequência de estudos moleculares visando a analisar os promotores de metilação de genes supressores de tumor e proteômica globais na carcinogênese gástrica está aumentando. No entanto, apenas alguns consideraram os diferentes tipos de células do estômago, a localização do tumor e a influência da infecção por Helicobacter pylori e pelo vírus Epstein-Barr (EBV). Diferenças moleculares relacionadas com áreas tumorais anatômicas e histológicas também foram recentemente descritas. Os autores propõem uma classificação molecular de câncer gástrico, dividindo-o em quatro subtipos: tumores positivos para o EBV; tumores microssatélite instáveis; tumores genomicamente estáveis ​​e tumores com instabilidade cromossômica.

  10. [Early gastric cancer surgically treated at Rebagliati Hospital: study of 76 cases during 5 years].

    PubMed

    Portanova, Michel; Mena, Victor; Yábar, Alejandro

    2010-01-01

    This report describes the characteristics of early gastric cancer surgically treated in the Gastric Cancer Unit at Rebagliati National Hospital between January 2004 and December 2008. Mean age was 68 years; males, distal location, submucosa infiltration and intestinal histological type predominate in these patients. Lymph node involvement was 13%.

  11. 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

  12. [Ways to personalized medicine for gastric cancer].

    PubMed

    Röcken, C

    2013-09-01

    Gastric cancer is the fourth most common tumor and the second most common cause of cancer-related deaths in the world. Approximately 70 % of the patients already have lymph node metastases at the time of the diagnosis leading to a median overall survival time of 16.7 months. Complete resection of the primary tumor with D2 lymphadenectomy offers the only chance of cure in the early stages of the disease. Survival of more locally advanced gastric cancer was improved by the introduction of perioperative, adjuvant and palliative chemotherapy of gastric cancer; however, the identification of novel predictive and diagnostic targets is urgently needed. Our own studies on gastric cancer biology identified several putative tumor biologically relevant G-protein-coupled receptors (e.g. AT1R, AT2R, CXCR4, FZD7, LGR4, LGR5, LGR6). Some of these receptors are also putative stem cell markers and may serve as future targets of an individualized therapy of gastric cancer.

  13. Chronic myelocytic leukemia and gastric cancer in the same patient.

    PubMed Central

    Butala, A.; Kalra, J.; Rosner, F.

    1989-01-01

    The association of chronic myelocytic leukemia (CML) and gastric cancer is very rare. We report a case of CML associated with gastric cancer and review the pertinent literature of 15 previously reported cases. PMID:2661837

  14. 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.

  15. 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

  16. Early gastric cancer in Menetrier's disease.

    PubMed

    Remes-Troche, Jose Maria; Zapata-Colindres, Juan Carlos; Starkman, Ivethe; De Anda, Jazmin; Arista-Nasr, Julian; Valdovinos-Diaz, Miguel Angel

    2009-01-01

    Uncommon conditions such as pernicious anaemia and hypertrophic gastropathies have been considered as risk factors for gastric cancer; however, the exact increase in risk is unknown. Menetrier's disease is a rare hyperproliferative disorder of the stomach caused by an overexpression of tumour growth factor α, a ligand for the tyrokinase epidermal growth factor receptor, resulting in a selective expansion of surface mucous cells in the body and fundus of the stomach. There have been nearly 200 cases of Menetrier's disease reported in the literature yet less than 15 have been associated with gastric adenocarcinoma. Here, we report an early stage gastric adenocarcinoma detected incidentally in a patient recently diagnosed with Menetrier's disease.

  17. 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

  18. Use of lectin microarray to differentiate gastric cancer from gastric ulcer

    PubMed Central

    Huang, Wei-Li; Li, Yang-Guang; Lv, Yong-Chen; Guan, Xiao-Hui; Ji, Hui-Fan; Chi, Bao-Rong

    2014-01-01

    AIM: To investigate the feasibility of lectin microarray for differentiating gastric cancer from gastric ulcer. METHODS: Twenty cases of human gastric cancer tissue and 20 cases of human gastric ulcer tissue were collected and processed. Protein was extracted from the frozen tissues and stored. The lectins were dissolved in buffer, and the sugar-binding specificities of lectins and the layout of the lectin microarray were summarized. The median of the effective data points for each lectin was globally normalized to the sum of medians of all effective data points for each lectin in one block. Formalin-fixed paraffin-embedded gastric cancer tissues and their corresponding gastric ulcer tissues were subjected to Ag retrieval. Biotinylated lectin was used as the primary antibody and HRP-streptavidin as the secondary antibody. The glycopatterns of glycoprotein in gastric cancer and gastric ulcer specimens were determined by lectin microarray, and then validated by lectin histochemistry. Data are presented as mean ± SD for the indicated number of independent experiments. RESULTS: The glycosylation level of gastric cancer was significantly higher than that in ulcer. In gastric cancer, most of the lectin binders showed positive signals and the intensity of the signals was stronger, whereas the opposite was the case for ulcers. Significant differences in the pathological score of the two lectins were apparent between ulcer and gastric cancer tissues using the same lectin. For MPL and VVA, all types of gastric cancer detected showed stronger staining and a higher positive rate in comparison with ulcer, especially in the case of signet ring cell carcinoma and intra-mucosal carcinoma. GalNAc bound to MPL showed a significant increase. A statistically significant association between MPL and gastric cancer was observed. As with MPL, there were significant differences in VVA staining between gastric cancer and ulcer. CONCLUSION: Lectin microarray can differentiate the different

  19. Is screening and surveillance for early detection of gastric cancer needed in Korean Americans?

    PubMed

    Kim, Gwang Ha; Bang, Sung Jo; Ende, Alexander R; Hwang, Joo Ha

    2015-11-01

    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.

  20. 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

  1. Targeting Smoothened Sensitizes Gastric Cancer to Chemotherapy in Experimental Models

    PubMed Central

    Ma, Huifa; Tian, Yongsheng; Yu, Xiangyang

    2017-01-01

    Background The Hedgehog pathway receptor smoothened (SMO) has critical roles in tumor progression. However, whether SMO is a key factor regulating gastric cancer chemotherapy resistance is unknown. Material/Methods We investigated the potential functions of SMO in inducing gastric cancer paclitaxel resistance in clinical samples, gastric cancer cell lines (424GC and AGS), and subcutaneous syngeneic mouse models. Results We found high SMO expression in paclitaxel-resistant gastric cancer clinical samples. Paclitaxel gastric cancer cells had higher SMO expression than in drug-sensitive cells. Upregulating SMO expression induced paclitaxel resistance in gastric cells lines via enhancing cell proliferation and inhibiting apoptosis. The combination of IPI-926, an inhibitor of SMO, with paclitaxel decreased cell viability of paclitaxel-resistant gastric cancer cells in vitro and controlled tumor growth in animal models. Conclusions The Hedgehog pathway receptor SMO is an important regulator of gastric cancer paclitaxel resistance and could be a target for sensitizing paclitaxel-resistant tumors. PMID:28350784

  2. Role of the CacyBP/SIP protein in gastric cancer.

    PubMed

    Zhai, Huihong; Meng, Juan; Jin, Haifeng; Li, Yuanfei; Wang, Jinbo

    2015-05-01

    Various reports indicate that calcyclin binding protein/Siah-1-interacting protein (CacyBP/SIP) is an important protein in tumorigenesis, but whether CacyBP/SIP promotes or suppresses cancer may depend on the cell type. In order to investigate whether CacyBP/SIP is significant in gastric cancerous tumorigenesis, the present study used immunohistochemistry to analyze 181 gastric cancer tissue samples, as well as 181 healthy tissue samples from the same gastric cancer patients. The immunohistochemical results were compared against patient data and pathological analysis of the tissue slices, including gender, age, degree of tumor differentiation and tumor, node, metastasis (TNM) stage. In addition, the level of CacyBP/SIP expression was detected in three frozen tissue samples of gastric adenocarcinoma using western blot analysis. Of the 181 cases analyzed in the present study, 80 cases were identified as non-metastatic gastric cancer and 101 cases were identified as gastric cancer that had metastasized to the lymph nodes. Tissue biopsies from the two sets of patients were examined using immunohistochemistry to identify the level of CacyBP/SIP expression in metastatic and primary gastric cancer tissues. Statistical analyses were performed on all data. The immunohistochemical analysis revealed that CacyBP/SIP was expressed in 31% (56/181) of gastric adenocarcinoma tissue samples and 7% (12/181) of adjacent non-cancerous gastric tissues (P<0.05). Furthermore, the expression levels of CacyBP/SIP were higher in cancerous tissue compared with the adjacent non-cancerous gastric tissue using western blotting. No association was identified between CacyBP/SIP expression and patient age (P=0.975), gender (P=0.185), degree of tumor differentiation (P=0.076) or TNM stage (P=0.979). Among the 101 patients with metastatic gastric cancer, CacyBP/SIP was expressed at primary sites in 31% (31/101) of cases and at metastatic sites in 26% (26/101) of cases (P=0.434). However, among the

  3. 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

  4. Correlation between SNPs in CDH1 and gastric cancer in Chinese population

    PubMed Central

    Yuan, Jintao; Wang, Lihui; Wang, Lan; Ma, Yunjia; Wang, Yuhua; Chen, Jianhong; Zhao, Hong

    2015-01-01

    Background Many recent studies revealed that the single nucleotide polymorphisms have considerable effects on the susceptibility of cancer, such as prostate cancer, lung cancer and gastric cancer. The E-cadherin, a calcium-dependent transmembrane glycoprotein encoded by CDH1 gene, is critical for epithelial construction, intercellular adhesion and cell migration. Some associations have been reported between single nucleotide polymorphisms and gastric cancer in the Chinese population. Objective To investigate whether the single nucleotide polymorphism in CDH1 gene is associated with the susceptibility of gastric cancer in the Chinese population. Material and methods The genotypes of 5 known single nucleotide polymorphisms (rs33935154, rs121964871, rs121964874, rs121964875, rs121964876) were determined in 359 gastric cancer patients and 368 healthy controls. High resolution melting curve detection and sequencing analysis were used in the present study. Results There is a statistical significance in the rs121964871 C>G polymorphism between gastric cancer patients and healthy controls (OR=1.769, 95%CI: 1.051–2.976). Elderly male individuals (>50 years of age) carrying this risk factor may be more susceptible to gastric cancer. Conclusions The results indicated that the rs121964871 C>G polymorphism is associated with the susceptibility of gastric cancer in the Chinese population, with some age and sex-dependent tendencies observed.

  5. Improving the outcomes in gastric cancer surgery.

    PubMed

    Tegels, Juul J W; De Maat, Michiel F G; Hulsewé, Karel W E; Hoofwijk, Anton G M; Stoot, Jan H M B

    2014-10-14

    Gastric cancer remains a significant health problem worldwide and surgery is currently the only potentially curative treatment option. Gastric cancer surgery is generally considered to be high risk surgery and five-year survival rates are poor, therefore a continuous strive to improve outcomes for these patients is warranted. Fortunately, in the last decades several potential advances have been introduced that intervene at various stages of the treatment process. This review provides an overview of methods implemented in pre-, intra- and postoperative stage of gastric cancer surgery to improve outcome. Better preoperative risk assessment using comorbidity index (e.g., Charlson comorbidity index), assessment of nutritional status (e.g., short nutritional assessment questionnaire, nutritional risk screening - 2002) and frailty assessment (Groningen frailty indicator, Edmonton frail scale, Hopkins frailty) was introduced. Also preoperative optimization of patients using prehabilitation has future potential. Implementation of fast-track or enhanced recovery after surgery programs is showing promising results, although future studies have to determine what the exact optimal strategy is. Introduction of laparoscopic surgery has shown improvement of results as well as optimization of lymph node dissection. Hyperthermic intraperitoneal chemotherapy has not shown to be beneficial in peritoneal metastatic disease thus far. Advances in postoperative care include optimal timing of oral diet, which has been shown to reduce hospital stay. In general, hospital volume, i.e., centralization, and clinical audits might further improve the outcome in gastric cancer surgery. In conclusion, progress has been made in improving the surgical treatment of gastric cancer. However, gastric cancer treatment is high risk surgery and many areas for future research remain.

  6. Improving the outcomes in gastric cancer surgery

    PubMed Central

    Tegels, Juul JW; De Maat, Michiel FG; Hulsewé, Karel WE; Hoofwijk, Anton GM; Stoot, Jan HMB

    2014-01-01

    Gastric cancer remains a significant health problem worldwide and surgery is currently the only potentially curative treatment option. Gastric cancer surgery is generally considered to be high risk surgery and five-year survival rates are poor, therefore a continuous strive to improve outcomes for these patients is warranted. Fortunately, in the last decades several potential advances have been introduced that intervene at various stages of the treatment process. This review provides an overview of methods implemented in pre-, intra- and postoperative stage of gastric cancer surgery to improve outcome. Better preoperative risk assessment using comorbidity index (e.g., Charlson comorbidity index), assessment of nutritional status (e.g., short nutritional assessment questionnaire, nutritional risk screening - 2002) and frailty assessment (Groningen frailty indicator, Edmonton frail scale, Hopkins frailty) was introduced. Also preoperative optimization of patients using prehabilitation has future potential. Implementation of fast-track or enhanced recovery after surgery programs is showing promising results, although future studies have to determine what the exact optimal strategy is. Introduction of laparoscopic surgery has shown improvement of results as well as optimization of lymph node dissection. Hyperthermic intraperitoneal chemotherapy has not shown to be beneficial in peritoneal metastatic disease thus far. Advances in postoperative care include optimal timing of oral diet, which has been shown to reduce hospital stay. In general, hospital volume, i.e., centralization, and clinical audits might further improve the outcome in gastric cancer surgery. In conclusion, progress has been made in improving the surgical treatment of gastric cancer. However, gastric cancer treatment is high risk surgery and many areas for future research remain. PMID:25320507

  7. Decreased expression of TLR7 in gastric cancer tissues and the effects of TLR7 activation on gastric cancer cells

    PubMed Central

    JIANG, JIONG; DONG, LEI; QIN, BIN; SHI, HAITAO; GUO, XIAOYAN; WANG, YAN

    2016-01-01

    The present study aimed to determine the expression of Toll-like receptor 7 (TLR7) in gastric cancer tissues and investigate the effects of its activation on gastric cancer cells. Patients with gastric cancer (n=30) and patients without gastric cancer (control; n=14) who underwent gastroscopy were enrolled in the study. Gastric cancer and cancer-adjacent tissues were obtained from the patients with gastric cancer, and normal gastric epithelial tissues were obtained from the control patients. The TLR7 mRNA and protein expressions in different tissues were investigated by reverse transcription-quantitative polymerase chain reaction, western blotting and immunohistochemistry. The present study also determined the effects of TLR7 activation by the agonist imiquimod on TLR7 protein expression, proinflammatory cytokine secretion and viability in SGC-7901 gastric cancer cells. The mRNA and protein expression levels of TLR7 were significantly downregulated in gastric cancer tissues compared with cancer-adjacent and normal gastric epithelial tissues (P<0.01). Imiquimod significantly increased TLR7 protein expression levels, and promoted the secretion of proinflammatory cytokines tumor necrosis factor-α and interleukin-6 in SGC-7901 cells. Furthermore, imiquimod inhibited the proliferation of SGC-7901 cells in a dose- and time-dependent manner. Thus, the present study identified that the expression of TLR7 was decreased in gastric cancer tissues, and TLR7 activation enhanced TLR7 expression, promoted the production of proinflammatory cytokines and inhibited the growth of gastric cancer cells. PMID:27347192

  8. Sarcopenia and Visceral Obesity in Esophageal and Gastric Cancer

    ClinicalTrials.gov

    2017-02-17

    Esophageal Cancer; Gastric Cancer; Sarcopenia; Sarcopenic Obesity; Obesity; Visceral Obesity; Quality of Life; Surgery; Complication of Treatment; Chemotherapeutic Toxicity; Physical Activity; Oncology

  9. 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

  10. Improvements in diagnosis have changed the incidence of histological types in advanced gastric cancer.

    PubMed Central

    Ikeda, Y.; Mori, M.; Kamakura, T.; Haraguchi, Y.; Saku, M.; Sugimachi, K.

    1995-01-01

    The data on 912 patients with early cancer and 1245 with advanced cancer who were seen between 1971 and 1990 were compared. The incidence of undifferentiated-type cancer increased significantly in patients with advanced gastric cancer, but not in patients with early gastric cancer. When the histological types were compared with regard to sex, age and location in patients with early gastric cancer the undifferentiated type was found to increase only in males, while in patients with advanced gastric cancer the undifferentiated type increased in both sexes as well as in younger patients and in both the upper and middle third of the stomach. These differences in the trends between early and advanced cancers are probably due to the different degrees of diagnostic accuracy for the early detection of histological types. PMID:7640228

  11. Prevalence of deleterious ATM germline mutations in gastric cancer patients.

    PubMed

    Huang, Dong-Sheng; Tao, Hou-Quan; He, Xu-Jun; Long, Ming; Yu, Sheng; Xia, Ying-Jie; Wei, Zhang; Xiong, Zikai; Jones, Sian; He, Yiping; Yan, Hai; Wang, Xiaoyue

    2015-12-01

    Besides CDH1, few hereditary gastric cancer predisposition genes have been previously reported. In this study, we discovered two germline ATM mutations (p.Y1203fs and p.N1223S) in a Chinese family with a history of gastric cancer by screening 83 cancer susceptibility genes. Using a published exome sequencing dataset, we found deleterious germline mutations of ATM in 2.7% of 335 gastric cancer patients of different ethnic origins. The frequency of deleterious ATM mutations in gastric cancer patients is significantly higher than that in general population (p=0.0000435), suggesting an association of ATM mutations with gastric cancer predisposition. We also observed biallelic inactivation of ATM in tumors of two gastric cancer patients. Further evaluation of ATM mutations in hereditary gastric cancer will facilitate genetic testing and risk assessment.

  12. Outcome of Gastric Cancer Surgery in Elderly Patients

    PubMed Central

    Kim, Min Sung

    2016-01-01

    Purpose Owing to increased life expectancy, the number of elderly patients with gastric cancer has increased. This study aimed to identify the outcomes of gastric cancer patients aged 80 years or older through comparison of their clinicopathological characteristics, surgical outcomes, and oncologic outcomes. Materials and Methods Between January 2006 and December 2013, the records of 478 patients who underwent surgery for gastric cancer were retrospectively evaluated. Patients were divided into two groups: patients <80 years old (n=446) and patients ≥80 years old (n=32). Results There were no significant differences in sex, body mass index, length of hospital stay, duration of surgery, depth of invasion, nodal metastasis, histologic type, or tumor size between the two groups. However, significant differences were found for the American Society of Anesthesiologist score and the serum albumin level between the two groups. Postoperative morbidity, mortality, disease-free survival, and recurrence rate did not differ between curatively resected patients in the two groups. Conclusions In elderly patients with gastric cancer, active treatment including radical gastrectomy is necessary. PMID:28053812

  13. Prognostic implication of hepatoduodenal ligament lymph nodes in gastric cancer

    PubMed Central

    Oh, Sung Eun; Choi, Min-Gew; Lee, Jun Ho; Sohn, Tae Sung; Bae, Jae Moon; Kim, Sung

    2017-01-01

    Abstract There has been controversy regarding whether hepatoduodenal lymph node (HDLN) metastasis in gastric cancer is distant or regional metastasis. HDLN positivity was classified as distant metastasis in the 7th American Joint Committee on Cancer (AJCC) classification, but it was reclassified as regional lymph node metastasis in the 8th AJCC classification. The aim of our study is to verify prognostic significance of HDLN metastasis in gastric cancer. This retrospective study enrolled patients with gastric cancer who underwent D2 gastrectomy from January 2007 to June 2010. HDLN was classified as a regional lymph node. Total number of patients was 3175; 143 (4.5%) of them had HDLN metastasis. The HDLN positivity was significantly associated with older age, more advanced tumor stage, undifferentiated histologic type, and pathologic diagnosis of lymphatic, vascular, and perineural invasions. Five-year survival rate of HDLN-positive patients with stages I to III disease was significantly higher than that of stage IV group (59.3% vs 18.8%, P = 0.001). In patients with stage III disease, 5-year survival rate of HDLN-positive group was significantly lower than that of HDLN-negative group (51.7% vs 66.3%, P = 0.001). Multivariate analysis showed that HDLN metastasis was an independent prognostic factor. HDLN has a different prognostic significance from other regional lymph nodes in advanced stage of gastric cancer though its positivity is not considered as distant metastasis. HDLN positivity itself seems to be an independent prognostic factor in gastric cancer, and the survival outcomes of patients with stage III disease need to be reconsidered according to HDLN positivity. PMID:28353581

  14. 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

  15. Classification of nodal stations in gastric cancer

    PubMed Central

    Costamagna, Guido; Doglietto, Giovanni Battista; Alfieri, Sergio

    2017-01-01

    The lymphatic drainage from the stomach is anatomically elaborate and it is very hard to predict the pattern of lymph node (LN) metastases from gastric cancer (GC). However, there are LN stations metastases that are more frequently observed depending on the tumor location. Furthermore, the incidence of metastasis to various regional LN stations depends on the depth of gastric-wall invasion. The Japanese Gastric Cancer Association (JGCA) classifies the regional LNs draining the stomach into 33 regional lymphatic stations. These are distinguished into three (N1–N3) groups with respect to the location of the primary tumor. The aim of this classification is to provide a common language for the clinical, surgical, and pathological description of GC. PMID:28217752

  16. Clinicopathological features and prognosis of coexistence of gastric gastrointestinal stromal tumor and gastric cancer

    PubMed Central

    Liu, Zhen; Liu, Shushang; Zheng, Gaozan; Yang, Jianjun; Hong, Liu; Sun, Li; Fan, Daiming; Zhang, Hongwei; Feng, Fan

    2016-01-01

    Abstract The coexistence of gastric gastrointestinal stromal tumor (GIST) and gastric cancer is relatively high, and its prognosis is controversial due to the complex and variant kinds of presentation. Thus, the present study aimed to explore the clinicopathological features and prognostic factors of gastric GIST with synchronous gastric cancer. From May 2010 to November 2015, a total of 241 gastric GIST patients were retrospectively enrolled in the present study. The patients with coexistence of gastric GIST and gastric cancer were recorded. The clinicopathological features and prognoses of patients were analyzed. Among 241 patients, 24 patients had synchronous gastric cancer (synchronous group) and 217 patients did not (no-synchronous group). The synchronous group presented a higher percentage of elders (66.7% vs 39.6%, P = 0.001) and males (87.5% vs 48.4%, P < 0.001) than the no-synchronous group. The tumor diameter, mitotic index, and National Institutes of Health degree were also significantly different between the 2 groups (all P < 0.05). The 5-year disease-free survival and disease-specific survival rates of synchronous group were significantly lower than those of no-synchronous group (54.9% vs 93.5%, P < 0.001; 37.9% vs 89.9%, P < 0.001, respectively). However, the 5-year overall survival rates between synchronous and gastric cancer groups were comparable (37.9% vs 57.6%, P = 0.474). The coexistence of gastric GIST and gastric cancer was common in elder male patients. The synchronous GIST was common in low-risk category. The prognosis of gastric GIST with synchronous gastric cancer was worse than that of primary-single gastric GIST, but was comparable with primary-single gastric cancer. PMID:27828865

  17. Clinicopathological features and prognosis of coexistence of gastric gastrointestinal stromal tumor and gastric cancer.

    PubMed

    Liu, Zhen; Liu, Shushang; Zheng, Gaozan; Yang, Jianjun; Hong, Liu; Sun, Li; Fan, Daiming; Zhang, Hongwei; Feng, Fan

    2016-11-01

    The coexistence of gastric gastrointestinal stromal tumor (GIST) and gastric cancer is relatively high, and its prognosis is controversial due to the complex and variant kinds of presentation. Thus, the present study aimed to explore the clinicopathological features and prognostic factors of gastric GIST with synchronous gastric cancer.From May 2010 to November 2015, a total of 241 gastric GIST patients were retrospectively enrolled in the present study. The patients with coexistence of gastric GIST and gastric cancer were recorded. The clinicopathological features and prognoses of patients were analyzed.Among 241 patients, 24 patients had synchronous gastric cancer (synchronous group) and 217 patients did not (no-synchronous group). The synchronous group presented a higher percentage of elders (66.7% vs 39.6%, P = 0.001) and males (87.5% vs 48.4%, P < 0.001) than the no-synchronous group. The tumor diameter, mitotic index, and National Institutes of Health degree were also significantly different between the 2 groups (all P < 0.05). The 5-year disease-free survival and disease-specific survival rates of synchronous group were significantly lower than those of no-synchronous group (54.9% vs 93.5%, P < 0.001; 37.9% vs 89.9%, P < 0.001, respectively). However, the 5-year overall survival rates between synchronous and gastric cancer groups were comparable (37.9% vs 57.6%, P = 0.474).The coexistence of gastric GIST and gastric cancer was common in elder male patients. The synchronous GIST was common in low-risk category. The prognosis of gastric GIST with synchronous gastric cancer was worse than that of primary-single gastric GIST, but was comparable with primary-single gastric cancer.

  18. 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.

  19. [Volumes of lymphadenectomy in gastric cancer surgery].

    PubMed

    Cherniavskiĭ, A A; Lavrov, N A

    2015-01-01

    It is summarized an experience of 1528 resections for gastric cancer supplemented by D1-, D2-, D2,5- and D3-lymphadenectomy in 751, 241, 359 and 177 patients resrectively. Unconventional type D2.5 means D2-lymphodis section with additional lymphadenectomy along hepatoduodenal ligament and superior retropancreatic nodes as well as omental bursa removal with lymphodis section of esophageal opening crura. Analysis of immediate and remote results is presented. It is concluded that D3-lymphadenectomy is minimally preferred over D2.5-type in gastric cancer staging. D3-lymphodis section has the largest number of especially purulent and pancreatogenic postoperative complications. D2.5-lymphadenectomy significantly increases 5-year survival in comparison with D2-lymphodis section (from 51.2 ± 4.9 to 64.0 ± 4.1%; p<0.001) and may be chosen for any radical surgery for gastric cancer including early forms. Localized proximal tumors which are in distinctive for metastasis into hepatoduodenal ligament lymph nodes are exception. D3-lymphodis section did not impact on survival in comparison with D2,5-lymphadenectomy. Only patients with antral cancer after distal subtotal gastric resection had 5-year survival increasing on 8 % (from 60.6 ± 7.5 to 68.5 ± 6.3%).

  20. Gastric cancer in Gwynedd. Possible links with bracken.

    PubMed Central

    Galpin, O. P.; Whitaker, C. J.; Whitaker, R.; Kassab, J. Y.

    1990-01-01

    One hundred and one histologically confirmed gastric cancer patients in Gwynedd, North Wales, were matched by sex, age and social class to two hospital inpatients without cancer. Seventy-seven of the gastric cancer cases were also matched, using the same criteria, to a patient with a confirmed cancer of a different site (excluding oesophagus). A questionnaire was used to determine bracken exposure and source of water in childhood. Residential and occupational histories were obtained and the consumption of buttermilk, a potential vector of the bracken carcinogens, was quantified. Comparison of the gastric cancer patients with the non-cancer controls indicated that exposure to bracken in childhood had an increased risk (RR = 2.34, P less than 0.001) compared to no exposure and that length of residence in Gwynedd was associated with increased risk (RR = 2.46 for durations of 61 years and over, P less than 0.01). Consumption of buttermilk in childhood and adulthood was attended by increased risk (RR = 1.61 and 1.86 respectively, the latter being statistically significant, P less than 0.05). Neither the residence effect nor consumption of buttermilk in adulthood remained significant when considered in a multivariate analysis with bracken exposure. PMID:2337510

  1. 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

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

    PubMed

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

    2010-02-06

    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.

  3. High Hepsin expression predicts poor prognosis in Gastric Cancer

    PubMed Central

    Zhang, Mingming; Zhao, Junjie; Tang, Wenyi; Wang, Yanru; Peng, Peike; Li, Lili; Song, Shushu; Wu, Hao; Li, Can; Yang, Caiting; Wang, Xuefei; Zhang, Chunyi; Gu, Jianxin

    2016-01-01

    Hepsin, a membrane-associated serine protease, is frequently upregulated in epithelial cancers and involved in cancer progression. Our study aims to describe the expression pattern and evaluate the clinical implication of hepsin in gastric cancer patients. The mRNA expression of hepsin was analyzed in 50 gastric cancer and matched non-tumor tissues, which was downregulated in 78% (39/50) of gastric cancer. By searching and analyzing four independent datasets from Oncomine, we obtained the similar results. Furthermore, we evaluated the hepsin expression by IHC in tissue microarray (TMA) containing 220 Gastric Cancer specimens. More importantly, Kaplan-Meier survival and Cox regression analyses were taken to access the prognosis of gastric cancer and predicted that hepsin protein expression was one of the significant and independent prognostic factors for overall survival of Gastric Cancer. PMID:27841306

  4. [Image processing of early gastric cancer cases].

    PubMed

    Inamoto, K; Umeda, T; Inamura, K

    1992-11-25

    Computer image processing was used to enhance gastric lesions in order to improve the detection of stomach cancer. Digitization was performed in 25 cases of early gastric cancer that had been confirmed surgically and pathologically. The image processing consisted of grey scale transformation, edge enhancement (Sobel operator), and high-pass filtering (unsharp masking). Gery scale transformation improved image quality for the detection of gastric lesions. The Sobel operator enhanced linear and curved margins, and consequently, suppressed the rest. High-pass filtering with unsharp masking was superior to visualization of the texture pattern on the mucosa. Eight of 10 small lesions (less than 2.0 cm) were successfully demonstrated. However, the detection of two lesions in the antrum, was difficult even with the aid of image enhancement. In the other 15 lesions (more than 2.0 cm), the tumor surface pattern and margin between the tumor and non-pathological mucosa were clearly visualized. Image processing was considered to contribute to the detection of small early gastric cancer lesions by enhancing the pathological lesions.

  5. The current situation for gastric cancer in Chile

    PubMed Central

    Caglevic, Christian; Silva, Shirley; Mahave, Mauricio; Rolfo, Christian; Gallardo, Jorge

    2016-01-01

    Gastric cancer is a neoplasm with a high incidence and mortality rate in Chile where more than 3000 people die every year from this type of cancer. This study shows the clinical and epidemiological considerations of this disease, information about translational research on this pathology in Chile, the contribution of Chilean doctors to the development of gastric cancer management awareness and the general situation of gastric cancer in Chile. PMID:28105078

  6. Origin of Microsatellite Instability in Gastric Cancer

    PubMed Central

    Halling, Kevin C.; Harper, Jeffrey; Moskaluk, Christopher A.; Thibodeau, Stephen N.; Petroni, Gina R.; Yustein, Aron S.; Tosi, Piero; Minacci, Chiara; Roviello, Franco; Piva, Paolo; Hamilton, Stanley R.; Jackson, Charles E.; Powell, Steven M.

    1999-01-01

    Microsatellite instability (MSI) is observed in 13–44% of gastric carcinoma. The etiology of MSI in gastric carcinoma has not been clearly defined. To assess the role of mismatch repair in the development of MSI in gastric cancer, expression of hMSH2 and hMLH1 was explored. We examined 117 gastric carcinomas for MSI and observed instability at one or more loci in 19 (16%) of these tumors. Of the 19 tumors with MSI, nine exhibited low-rate MSI (MSI-L) with instability at <17% of loci, whereas the remaining 10 exhibited high-rate MSI (MSI-H) with instability at >33% of loci examined. Immunohistochemical staining for hMLH1 and hMSH2 was performed on eight of the tumors with MSI-H, five with MSI-L, and 15 tumors without MSI. All eight tumors with MSI-H showed loss of staining for either hMLH1 (n = 5) or hMSH2 (n = 3). In contrast, tumors with MSI-L or without MSI all showed normal hMSH2 and hMLH1 protein expression patterns. Moreover, all eight of the tumors with MSI-H also showed instability at BAT-26, whereas none of the MSI-L tumors or tumors without instability showed instability at BAT-26. These findings suggest that the majority of high-level MSI in gastric cancer is associated with defects of the mismatch repair pathway. Although larger studies are needed, BAT-26 appears to be a sensitive and specific marker for the MSI-H phenotype in gastric carcinoma. PMID:10393852

  7. The Clinical Evidence Linking Helicobacter pylori to Gastric Cancer.

    PubMed

    Moss, Steven F

    2017-03-01

    Gastric cancer has long been recognized to be accompanied and preceded by chronic gastritis, lasting decades. Arguably, the most important development in our understanding of gastric cancer pathogenesis over the past 50 years has been the realization that, for most cases of gastric cancer, Helicobacter pylori is the cause of the underlying gastritis. Gastritis can promote gastric carcinogenesis, typically via the Correa cascade of atrophic gastritis, intestinal metaplasia, and dysplasia. Nested case-control studies have shown that H pylori infection increases the risk of gastric cancer significantly, both of the intestinal and diffuse subtypes, and that H pylori is responsible for approximately 90% of the world's burden of noncardia gastric cancer. Based largely on randomized studies in high gastric cancer prevalence regions in East Asia, it appears that primary and tertiary intervention to eradicate H pylori can halve the risk of gastric cancer. Some public health authorities now are starting screening and treatment programs to reduce the burden of gastric cancer in these high-risk areas. However, there is currently much less enthusiasm for initiating similar attempts in the United States. This is partially because gastric cancer is a relatively less frequent cause of cancer in the United States, and in addition there are concerns about theoretical downsides of H pylori eradication, principally because of the consistent inverse relationship noted between H pylori and esophageal adenocarcinoma. Nevertheless, establishing a link between chronic H pylori infection and gastric cancer has led to novel insights into cancer biology, the gastrointestinal microbiome, and on individual and population-based gastric cancer prevention strategies.

  8. 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.

  9. Relationship between Salt Preference and Gastric Cancer Screening: An Analysis of a Nationwide Survey in Korea

    PubMed Central

    Shin, Ji-Yeon; Kim, Jeongseon; Choi, Kui Son; Suh, Mina; Park, Boyoung; Jun, Jae Kwan

    2016-01-01

    Purpose Epidemiological studies have demonstrated an association between excessive salt intake and gastric cancer risk, and this potential risk increases the need for adequate gastric cancer screening in individuals with high salt intake. However, the association between salt intake and gastric cancer screening in the general population has rarely been investigated. We explored the association between salt preference and participation in gastric cancer screening among a nationally representative Korean population. Materials and Methods The study population was derived from the Korean National Cancer Screening Survey (KNCSS) 2006-2007, an annual nationwide interview survey investigating cancer screening rates. Of 4,055 individuals who participated in the KNCSS 2006-2007, 3,336 individuals aged over 40 years were included in our analysis. The odds ratio (OR) and 95% confidence interval (CI) were estimated using polytomous logistic regression. Results Individuals with higher salt preference were less likely to participate in regular gastric cancer screening. After adjusting for age, sex, monthly household income, education, family history of cancer, and self-rated health status, ORs for undergoing regular gastric cancer screening were 1.00, 0.82 (95% CI, 0.61 to 1.12), 0.74 (95% CI, 0.54 to 1.00), 0.77 (95% CI, 0.56 to 1.05), and 0.38 (95% CI, 0.16 to 0.92) according to the level of salt preference (p for trend=0.048). Conclusion Individuals with higher salt preference showed suboptimal gastric cancer screening adherence compared to those with a lower salt preference. These findings highlight the need for better delivery of educational messages to change risk perceptions regarding gastric cancer screening practice. PMID:26693914

  10. Menstrual and Reproductive Factors and Risk of Gastric and Colorectal Cancer in Spain

    PubMed Central

    Lope, Virginia; Fernández de Larrea, Nerea; Pérez-Gómez, Beatriz; Martín, Vicente; Moreno, Victor; Costas, Laura; Longo, Federico; Jiménez-Moleón, José Juan; Llorca, Javier; Ascunce, Nieves; Peiró-Pérez, Rosana; Altzibar, Jone M.; Tardón, Adonina; Alguacil, Juan; Navarro, Carmen; Sierra, Ángeles; Vega, Ana Belén; Villafañe, Amaya; Castaño-Vinyals, Gemma; Kogevinas, Manolis; Pollán, Marina; Aragonés, Nuria

    2016-01-01

    Background Sex hormones play a role in gastric cancer and colorectal cancer etiology, however, epidemiological evidence is inconsistent. This study examines the influence of menstrual and reproductive factors over the risk of both tumors. Methods In this case-control study 128 women with gastric cancer and 1293 controls, as well as 562 female and colorectal cancer cases and 1605 controls were recruited in 9 and 11 Spanish provinces, respectively. Population controls were frequency matched to cases by age and province. Demographic and reproductive data were directly surveyed by trained staff. The association with gastric, colon and rectal cancer was assessed using logistic and multinomial mixed regression models. Results Our results show an inverse association of age at first birth with gastric cancer risk (five-year trend: OR = 0.69; p-value = 0.006). Ever users of hormonal contraception presented a decreased risk of gastric (OR = 0.42; 95%CI = 0.26–0.69), colon (OR = 0.64; 95%CI = 0.48–0.86) and rectal cancer (OR = 0.61; 95%CI = 0.43–0.88). Postmenopausal women who used hormone replacement therapy showed a decreased risk of colon and rectal tumors. A significant interaction of educational level with parity and months of first child lactation was also observed. Conclusion These findings suggest a protective role of exogenous hormones in gastric and colorectal cancer risk. The role of endogenous hormones remains unclear. PMID:27776142

  11. Gastric Cancer in Young Patients

    PubMed Central

    Dhobi, Manzoor A.; Wani, Khursheed Alam; Parray, Fazl Qadir; Wani, Rouf A.; Peer, G. Q.; Abdullah, Safiya; Wani, Imtiyaz A.; Wani, Muneer A.; Shah, Mubashir A.; Thakur, Natasha

    2013-01-01

    Aim. The aim of this study was to see the clinical, pathological, and demographic profile of young patients with stomach carcinoma besides association with p53. Patients and Methods. Prospective study of young patients with stomach carcinoma from January 2005 to December 2009. A total of 50 patients with age less than 40 years were studied. Results. Male female ratio was 1 : 1.08 in young patients and 2.5 : 1 in older patients. A positive family history of stomach cancer in the first degree relatives was present in 10% of young patients. Resection was possible only in 50% young patients. 26% young patients underwent only palliative gastrojejunostomy. The most common operation was lower partial gastrectomy in 68%. Amongst the intraoperative findings peritoneal metastasis was seen in 17.4% in young patients. 50% young patients presented in stage IV as per AJCC classification (P value .004; sig.). None of the patients presented as stage 1 disease in young group. Conclusion. Early detection of stomach carcinoma is very important in all patients but in young patients it is of paramount importance. PMID:24381753

  12. High incidence of oesophageal and gastric cancer in Kashmir in a population with special personal and dietary habits.

    PubMed Central

    Khuroo, M S; Zargar, S A; Mahajan, R; Banday, M A

    1992-01-01

    Over a three year period (1 July 1986 to 30 June 1989) all newly diagnosed and histologically proved cases of oesophageal and gastric cancer were recorded prospectively. Some 1515 cases of oesophageal cancer (1050 men and 465 women) and 966 cases of gastric cancer (789 men and 177 women) were registered. Seven patients had simultaneous oesophageal and gastric cancer. Age standardised incidence rates for oesophageal cancer were: men 43.6/100,000 per year; women 27.9/100,000 per year. The rates for gastric cancer were: men 36.7/100,000 per year, women 9.9/100,000 per annum. These figures were three to six times higher than those recorded by cancer registries in Banglore, Madras, and Bombay. The incidence rates for oesophageal and gastric cancer in Islamabad (southern district of Kashmir) were 4.1 to 5.4 times higher in men and 1.5 to 2.0 times higher in women than those for Kupwara (northern district of Kashmir). The incidence rates for oesophageal and gastric cancer in Muslims, Hindus, and Sikhs were different. The epidemiology of oesophageal cancer in Kashmir was similar to that found in the 'Asian oesophageal cancer belt'. At the same time Kashmir also had an unprecedented high incidence of gastric cancer. Kashmiries have special personal and dietary habits. Further studies are needed to define the relation between these habits and the occurrence of oesophageal and gastric cancer. PMID:1740265

  13. 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.

  14. Cronkhite-Canada syndrome associated with esophageal and gastric cancers: report of a case.

    PubMed

    Ito, Masahiro; Matsumoto, Sohei; Takayama, Tomoyoshi; Wakatsuki, Kohei; Tanaka, Tetsuya; Migita, Kazuhiro; Nakajima, Yoshiyuki

    2015-06-01

    Cronkhite-Canada Syndrome (CCS) is a rare non-inherited gastrointestinal polyposis syndrome with characteristic ectodermal changes. We report an extremely unusual case of CCS associated with primary esophageal and gastric cancers. A 74-year-old Japanese man with symptoms of anorexia and diarrhea was found to have primary esophageal and gastric cancers, as well as multiple gastric and colonic polyps. Based on the physical findings of onychodystrophy and alopecia, we diagnosed CCS. Because of his age and nutritional status, we decided to perform total gastrectomy for gastric cancer and chemoradiotherapy for esophageal cancer, upon completion of which the patient was started on steroid therapy for the CCS. After 1 week of steroid therapy, the patient's watery diarrhea improved. We recommend that for patients with CCS, the therapeutic strategy be carefully considered based on the patient's nutritional status, the severity of the CCS, and the extent of gastrointestinal cancer.

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

    PubMed

    Chu, Dake; Zhu, Shaojun; Li, Jipeng; Ji, Gang; Wang, Weizhong; Wu, Guosheng; Zheng, Jianyong

    2014-01-01

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

  16. EXPRESSION MECHANISM AND CLINICAL SIGNIFICANCE OF NOB1 IN GASTRIC CANCER TISSUE AND ADJACENT NORMAL TISSUE.

    PubMed

    Zhou, W-P; Liu, X; Yang, Y; Liu, Y-F

    2015-01-01

    This paper studies the effect and relationship of NOB1 in the development of gastric cancer, based on an analysis of NOB1expression in gastric cancer tissue and adjacent tissue. Thirty gastric cancer tissue samples taken during surgery with complete pathological data and their related adjacent normal tissue were examined in this study. NOB1 protein expression in gastric cancer tissue and adjacent normal tissue was detected by immunohistochemistry (IHC). Real-time PCR was used to detect NOB1 mRNA expression, which provided a basis on which to explore the clinical pathological characteristics for patients with gastric cancer. Results show that NOB1 protein in gastric cancer tissue and adjacent normal tissue were diffusely expressed both in the cytoplasm and nucleus. The positive expression rate in gastric cancer tissue was 73%, higher than that in adjacent normal tissue (47%). Both the reference NAPDH and NOB1 amplification are reflected in the amplification curve in standard S-shape and the unimodal solubility curve which was not altered by non-specific amplification and primer dimer. NOB1 mRNA relative expression in cancer tissue was 4.899∓1.412. NOB1 expression had no direct relationship with the patients’ age, gender, tumor differentiation or infiltration degree, lymphatic metastasis, distant metastasis nor pTNM periodization, but was directly related to the size of the tumor. All the findings in this paper suggest that NOB1 can be one of the focuses for diagnosing and treating gastric cancer and that its protein expression is likely to increase with the growth of tumor, thus playing a great role in the incidence and development of gastric cancer.

  17. 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

  18. 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

  19. Whole-genome reconstruction and mutational signatures in gastric cancer

    PubMed Central

    2012-01-01

    Background Gastric cancer is the second highest cause of global cancer mortality. To explore the complete repertoire of somatic alterations in gastric cancer, we combined massively parallel short read and DNA paired-end tag sequencing to present the first whole-genome analysis of two gastric adenocarcinomas, one with chromosomal instability and the other with microsatellite instability. Results Integrative analysis and de novo assemblies revealed the architecture of a wild-type KRAS amplification, a common driver event in gastric cancer. We discovered three distinct mutational signatures in gastric cancer - against a genome-wide backdrop of oxidative and microsatellite instability-related mutational signatures, we identified the first exome-specific mutational signature. Further characterization of the impact of these signatures by combining sequencing data from 40 complete gastric cancer exomes and targeted screening of an additional 94 independent gastric tumors uncovered ACVR2A, RPL22 and LMAN1 as recurrently mutated genes in microsatellite instability-positive gastric cancer and PAPPA as a recurrently mutated gene in TP53 wild-type gastric cancer. Conclusions These results highlight how whole-genome cancer sequencing can uncover information relevant to tissue-specific carcinogenesis that would otherwise be missed from exome-sequencing data. PMID:23237666

  20. CDH1 methylation in preoperative peritoneal washes is an independent prognostic factor for gastric cancer

    PubMed Central

    Yu, Qi-Ming; Wang, Xin-Bao; Luo, Jun; Wang, Shi; Fang, Xian-Hua; Yu, Jiang-Liu; Ling, Zhi-Qiang

    2012-01-01

    Background and Objectives To investigate the clinical value of CDH1 methylation in preoperative peritoneal washes (PPW) from gastric cancer patients. Methods CDH1 methylation was detected by real-time methylation specific-PCR in tumor tissues and corresponding PPW from 92 gastric cancer patients, gastric mucosa from 40 chronic gastritis patients and 48 normal persons. Results CDH1 methylation was found in 75 of 92 (81.5%) gastric cancer tissues, which significantly correlated with size, growth pattern, differentiation, lymphatic invasion, venous invasion, invasion depth, lymph node metastasis, distant metastasis, and TNM stage of tumor (all P < 0.05), but its relationship to age, gender, tumor site, and H. pylori infection was not found (all P > 0.05). The percentage of CDH1 methylation in PPW was 48.9%, of which the Aζ value of ROC curve was 0.8 compared to that in gastric cancer tissues. Kaplan–Meier analysis showed that there was a significant difference in disease-free survival (DFS) between the patients with or without methylated CDH1 in their PPW (χ2 = 109.64, P < 0.000). Cox regression analysis revealed CDH1 methylation in PPW was an independent risk factor for gastric cancer patients, with a remarkable decrease in DFS after postoperative 30 months. Conclusions Methylated CDH1 in PPW predicts poor prognosis for gastric cancer patients. J. Surg. Oncol. 2012; 106:765–771. © 2012 Wiley Periodicals, Inc. PMID:22514028

  1. A Phase I/II Study of Oblimersen Plus Cisplatin and Fluorouracil in Gastric & Esophageal Junction Cancer

    ClinicalTrials.gov

    2015-06-10

    Adenocarcinoma of the Esophagus; Adenocarcinoma of the Gastroesophageal Junction; Diffuse Adenocarcinoma of the Stomach; Intestinal Adenocarcinoma of the Stomach; Mixed Adenocarcinoma of the Stomach; Recurrent Esophageal Cancer; Recurrent Gastric Cancer; Squamous Cell Carcinoma of the Esophagus; Stage III Esophageal Cancer; Stage IIIA Gastric Cancer; Stage IIIB Gastric Cancer; Stage IIIC Gastric Cancer; Stage IV Esophageal Cancer; Stage IV Gastric Cancer

  2. 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

  3. 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.

  4. Repression of PES1 expression inhibits growth of gastric cancer.

    PubMed

    Li, Jieping; Zhou, Xiaodong; Lan, Xiaopeng; Zeng, Guobin; Jiang, Xuping; Huang, Zongming

    2016-03-01

    Gastric cancer is one of the leading causes of cancer death worldwide. However, precise molecular mechanisms underlining its development are far from clear. We recently reported that PES1 promoted development of breast cancer and ovarian cancer as an oncogene. In this study, we reported that ablation of endogenous PES1 resulted in significant suppression of cell proliferation and growth and led to cell cycle arrest in G2 or G1 phase, respectively, in two gastric cancer cell lines (AGS and N87) in vitro. Meanwhile, silencing of PES1 obviously decreased expressions of cyclin D1, HIF-1α, and vascular endothelial growth factor (VEGF) expressions and increased p21WAF1 expression. Re-expression of PES1 in these two kinds of PES1 knockdown cells rescued these effects. In vivo, repression of endogenous PES1 expression suppressed gastric tumor growth in nude mice. In addition, 40.7 % (24/59) of gastric cancer tissues showed PES1 expression via immunohistochemical (IHC) staining. However, there were not any positive PES1 stainings in matched adjacent tissues. Our results demonstrated that repression of PES1 changed expressions of some cell proliferation- and angiogenesis-related genes and inhibited gastric cancer growth, and PES1 expression increased in gastric cancer tissues. These results suggest that PES1 may play an important role in development of gastric cancer. PES1 may be a potential target for gastric cancer therapy.

  5. Expression and clinical significance of matrix metalloproteinase-17 and -25 in gastric cancer

    PubMed Central

    WANG, YING; YU, SHI-JIE; LI, YAN-XIA; LUO, HE-SHENG

    2015-01-01

    The aim of the present study was to investigate the expression and clinicopathological features of matrix metalloproteinase 17 (MMP17; also known as MT4-MMP) and MMP25 (also known as MT6-MMP) in gastric cancer. Immunohistochemistry and reverse transcription-quantitative polymerase chain reaction were used to detect the expression of MMP17 and MMP25 in 42 cases of gastric carcinoma and normal tissues, and 40 cases of atrophic gastritis. The expression of MMP17 in the normal gastric and atrophic gastritis tissues was significantly lower than that in the gastric cancer tissues (P<0.05). The expression of MMP25 in the gastric cancer and atrophic gastritis tissues was markedly higher compared with the normal gastric tissues (P<0.05). The expression of MMP17 and MMP25 was significantly associated with the depth of tumor invasion, lymph node metastasis and serous membrane involvement (P<0.05), but not with patient age and gender, or lesion length, site and histological grade (P>0.05). Therefore, this indicates that the expression of MMP17 and MMP25 is increased with the degree of progress of gastric carcinoma. The detection of MMP17 and MMP25 expression may have clinical value in predicting the prognosis of patients with gastric cancer. PMID:25621036

  6. Gastric cancer: prevention, screening and early diagnosis.

    PubMed

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

    2014-10-14

    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.

  7. The Rare and Challenging Presentation of Gastric Cancer during Pregnancy: A Report of Three Cases

    PubMed Central

    Norero, Enrique; Canales, Claudio; Martínez, José Miguel; Herrera, María Elisa; Muñoz, Carolina; Jarufe, Nicolás

    2016-01-01

    Pregnancy-associated gastric cancer is extremely rare. In many cases, it is diagnosed at an advanced stage because the symptoms during pregnancy are generally overlooked. We report three cases of gastric cancer during pregnancy with various outcomes. The first case included a patient with stage IV gastric cancer who received palliative chemotherapy. This patient had a preterm birth and died 7 months after diagnosis. The second case received neoadjuvant chemotherapy during pregnancy and a total gastrectomy was performed after delivery. She then received adjuvant chemoradiotherapy. This patient developed pulmonary metastasis and died of recurrence 41 months after surgery. In the third case, a distal subtotal gastrectomy was performed at week 14 of pregnancy, with no complications. The patient received adjuvant chemoradiotherapy. She is currently without recurrence 14 months after surgery. In patients with pregnancy-associated gastric cancer, treatment decisions are predominantly influenced by clinical stage and gestational age at diagnosis. PMID:28053815

  8. Coffee intake and gastric cancer risk: The Singapore Chinese Health Study

    PubMed Central

    Ainslie-Waldman, Cheryl E.; Koh, Woon-Puay; Jin, Aizhen; Yeoh, Khay Guan; Zhu, Feng; Wang, Renwei; Yuan, Jian-Min; Butler, Lesley M.

    2014-01-01

    Background Despite experimental evidence showing chemopreventive effects of coffee-related compounds on gastric carcinogenesis, epidemiologic studies generally do not support coffee-gastric cancer associations. Observational data are lacking among high-risk populations with sufficient regular coffee consumption. Methods We examined the association between caffeinated coffee intake and gastric cancer risk in a population-based cohort that enrolled 63,257 Chinese men and women aged 45–74 years between 1993 and 1998 in Singapore. Incident gastric cancer cases (n=647) were identified after a mean follow-up of 14.7 years. Biomarkers of Helicobacter pylori (H. pylori) infection were measured in a subset of gastric cancer cases with blood collected prior to cancer diagnosis and their matched controls. Results In the total cohort, daily versus non-daily coffee intake was associated with a statistically non-significant decrease in gastric cancer risk [hazards ratio (HR) = 0.85; 95% confidence interval (CI): 0.69, 1.04). In women, the inverse association strengthened and reached statistical significance (HR=0.63; 95% CI: 0.46, 0.87). In analyses restricted to never smokers and nondrinkers of alcohol, inverse associations strengthened in the total cohort (HR=0.69; 95% CI: 0.52, 0.91) and in women (HR=0.52; 95% CI: 0.37, 0.74). There was no coffee-gastric cancer risk association among men, regardless of smoking status or alcohol consumption. Similar results were observed in the nested case-control study after adjustment for H. pylori infection. Conclusion Daily coffee consumption may reduce the risk of gastric cancer in high-risk populations, especially among women. Impact: Research aimed at identifying the compounds in coffee that may protect against gastric carcinogenesis is warranted. PMID:24608187

  9. Epithelial-mesenchymal transition in gastric cancer

    PubMed Central

    Huang, Lei; Wu, Ruo-Lin; Xu, A-Man

    2015-01-01

    Gastric cancer (GC) is one of the most common malignancies worldwide with poor prognosis for lack of early detection and effective treatment modalities. The significant influence of tumor microenvironment on malignant cells has been extensively investigated in this targeted-therapy era. Epithelial-mesenchymal transition (EMT) is a highly conserved and fundamental process that is critical for embryogenesis and some other pathophysiological processes, especially tumor genesis and progression. Aberrant gastric EMT activation could endow gastric epithelial cells with increased mesenchymal characteristics and less epithelial features, and promote cancer cell stemness, initiation, invasion, metastasis, and chemo-resistance with cellular adhesion molecules especially E-cadherin concomitantly repressed, which allows tumor cells to disseminate and spread throughout the body. Some pathogens, stress, and hypoxia could induce and aggravate GC via EMT, which is significantly correlated with prognosis. GC EMT is modulated by diverse micro-environmental, membrane, and intracellular cues, and could be triggered by various overexpressed transcription factors, which are downstream of several vital cross-talking signaling pathways including TGF-β, Wnt/β-catenin, Notch, etc. microRNAs also contribute significantly to GC EMT modulation. There are currently some agents which could suppress GC EMT, shedding light on novel anti-malignancy strategies. Investigating potential mechanisms modulating GC cell EMT and discovering novel EMT regulators will further elucidate GC biology, and may provide new biomarkers for early GC detection and potentially efficient targets for preventative and curative anti-GC intervention approaches to prevent local and distant invasions. PMID:26807164

  10. 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.

  11. Salty Food Preference and Intake and Risk of Gastric Cancer: The JACC Study

    PubMed Central

    Umesawa, Mitsumasa; Iso, Hiroyasu; Fujino, Yoshihisa; Kikuchi, Shogo; Tamakoshi, Akiko

    2016-01-01

    Background High sodium intake is a potential risk factor of gastric cancer. However, limited information is available on the relationship between salty food preference or intake and risk of gastric cancer. The aim of the present study was to determine the association between these variables among the Japanese population. Methods Between 1988 and 1990, 15 732 men and 24 997 women aged 40–79 years old with no history of cancer or cardiovascular disease completed a lifestyle questionnaire that included information about food intake. The subjects were enrolled in the Japan Collaborative Cohort (JACC) Study for Evaluation of Cancer Risk Sponsored by Monbusho. After a median follow-up of 14.3 years, 787 incident gastric cancers were documented. We examined the associations between salty food preference and intake and gastric cancer incidence using the Cox proportional hazard model. Results The risk of gastric cancer among subjects with a strong preference for salty food was approximately 30% higher than among those who preferred normal-level salty food (hazard ratio [HR] 1.31; 95% confidence interval [CI], 1.02–1.67). The risk of gastric cancer in subjects who consumed 3 and ≥4 bowls/day of miso soup was approximately 60% higher than in those who consumed less miso soup (HR 1.67; 95% CI, 1.16–2.39 and HR 1.64; 95% CI, 1.11–2.42, respectively). Sodium intake correlated positively and linearly with risk of gastric cancer (P for trend = 0.002). Conclusions The present study showed that salty food preference, consumption of large quantities of miso soup, and high sodium intake were associated with increased risk of gastric cancer among Japanese people. PMID:26477994

  12. Gastric hyperplastic polyp with focal cancer.

    PubMed

    Markowski, Adam Roman; Guzinska-Ustymowicz, Katarzyna

    2016-05-01

    This paper reports a rare case of early adenocarcinoma within the gastric hyperplastic polyp, that was completely resected during an endoscopic procedure, and discusses current recommendations in such cases. Endoscopic resection of polyps with focal dysplasia or cancer is commonly indicated, as long as the procedure can be performed safely. After complete excision of a polyp with atypical focal lesion, endoscopic surveillance is suggested. The frequency of surveillance endoscopy should depend on the precise histopathological diagnosis and possibility of confirming the completeness of the endoscopic resection. If the completeness of the procedure is confirmed both macro- and microscopically, gastric resection does not have to be performed. A follow-up esophago-gastroduodenoscopy should be performed at 1 year and then at 3 years.

  13. Gastric hyperplastic polyp with focal cancer

    PubMed Central

    Markowski, Adam Roman; Guzinska-Ustymowicz, Katarzyna

    2016-01-01

    This paper reports a rare case of early adenocarcinoma within the gastric hyperplastic polyp, that was completely resected during an endoscopic procedure, and discusses current recommendations in such cases. Endoscopic resection of polyps with focal dysplasia or cancer is commonly indicated, as long as the procedure can be performed safely. After complete excision of a polyp with atypical focal lesion, endoscopic surveillance is suggested. The frequency of surveillance endoscopy should depend on the precise histopathological diagnosis and possibility of confirming the completeness of the endoscopic resection. If the completeness of the procedure is confirmed both macro- and microscopically, gastric resection does not have to be performed. A follow-up esophago-gastroduodenoscopy should be performed at 1 year and then at 3 years. PMID:25361760

  14. Gastric cancer stem cells in gastric carcinogenesis, progression, prevention and treatment

    PubMed Central

    Li, Kang; Dan, Zeng; Nie, Yu-Qiang

    2014-01-01

    In recent decades, the study of the mechanism of tumorigenesis has brought much progress to cancer treatment. However, cancer stem cell (CSC) theory has changed previous views of tumors, and has provided a new method for treatment of cancer. The discovery of CSCs and their characteristics have contributed to understanding the molecular mechanism of tumor genesis and development, resulting in a new effective strategy for cancer treatment. Gastric CSCs (GCSCs) are the basis for the onset of gastric cancer. They may be derived from gastric stem cells in gastric tissues, or bone marrow mesenchymal stem cells. As with other stem cells, GCSCs highly express drug-resistance genes such as aldehyde dehydrogenase and multidrug resistance, which are resistant to chemotherapy and thus form the basis of drug resistance. Many specific molecular markers such as CD44 and CD133 have been used for identification and isolation of GCSCs, diagnosis and grading of gastric cancer, and research on GCSC-targeted therapy for gastric cancer. Therefore, discussion of the recent development and advancements in GCSCs will be helpful for providing novel insight into gastric cancer treatment. PMID:24833872

  15. Current status of randomized controlled trials for laparoscopic gastric surgery for gastric cancer in China.

    PubMed

    Li, Guoxin; Hu, Yanfeng; Liu, Hao

    2015-08-01

    China alone accounts for nearly 42% of all new gastric cancer cases worldwide, and gastric cancer is the third leading cause of cancer deaths in China nowadays. Without mass screening programs, unfortunately over 80% of all Chinese patients have been diagnosed as advanced diseases. As in other Asian countries, especially Japan and Korea, laparoscopic gastrectomy for the treatment of gastric cancer has gained increasingly popularity in China during the past decade. Whether laparoscopic surgery can be safely and effectively performed in the treatment of gastric cancer remains controversial, particularly with regard to curative intent in advanced diseases. Given the high incidence of these cancers, and their advanced stage at diagnosis, China has a significant interest in determining the safety and effectiveness of laparoscopic gastrectomy. A well-designed randomized controlled trial (RCT) is considered the only feasible way to provide conclusive evidence. To date, China has not played a significant role in terms of conducting RCT concerning laparoscopic surgery for gastric cancer. However, an effort has been made by the Chinese researchers, with the great help from our colleagues in neighboring countries such as Korea and Japan, through the establishment of the Chinese Laparoscopic Gastrointestinal Surgery Study Group. In this review, we present the current status of RCT for laparoscopic gastric surgery for gastric cancer in China, including published and ongoing registered RCT.

  16. Laparoscopic ultrasound and gastric cancer

    NASA Astrophysics Data System (ADS)

    Dixon, T. Michael; Vu, Huan

    2001-05-01

    The management of gastrointestinal malignancies continues to evolve with the latest available therapeutic and diagnostic modalities. There are currently two driving forces in the management of these cancers: the benefits of minimally invasive surgery so thoroughly demonstrated by laparoscopic surgery, and the shift toward neoadjuvant chemotherapy for upper gastrointestinal cancers. In order to match the appropriate treatment to the disease, accurate staging is imperative. No technological advances have combined these two needs as much as laparascopic ultrasound to evaluate the liver and peritoneal cavity. We present a concise review of the latest application of laparoscopic ultrasound in management of gastrointestinal malignancy.

  17. Scorpion venoms in gastric cancer

    PubMed Central

    Zhang, Xiao-Ying; Zhang, Pei-Ying

    2016-01-01

    Venom secretions from snakes, scorpions, spiders and bees, have been widely applied in traditional medicine and current biopharmaceutical research. Possession of anticancer potential is another novel discovery for animal venoms and toxins. An increasing number of studies have shown the anticancer effects of venoms and toxins of snakes, and scorpions in vitro and in vivo, which were achieved mainly through the inhibition of cancer growth, arrest of cell cycle, induction of apoptosis and suppression of cancer metastasis. However, more evidence is needed to support this concept and the mechanisms of anticancer actions are not clearly understood. The present review is focused on the recant updates on anticancer venom research. PMID:27900054

  18. E-Cadherin and Gastric Cancer: Cause, Consequence, and Applications

    PubMed Central

    Liu, Xin

    2014-01-01

    E-cadherin (epithelial-cadherin), encoded by the CDH1 gene, is a transmembrane glycoprotein playing a crucial role in maintaining cell-cell adhesion. E-cadherin has been reported to be a tumor suppressor and to be down regulated in gastric cancer. Besides genetic mutations in CDH1 gene to induce hereditary diffuse gastric cancer (HDGC), epigenetic factors such as DNA hypermethylation also contribute to the reduction of E-cadherin in gastric carcinogenesis. In addition, expression of E-cadherin could be mediated by infectious agents such as H. pylori (Helicobacter pylori). As E-cadherin is vitally involved in signaling pathways modulating cell proliferation, survival, invasion, and migration, dysregulation of E-cadherin leads to dysfunction of gastric epithelial cells and contributes to gastric cancer development. Moreover, changes in its expression could reflect pathological conditions of gastric mucosa, making its role in gastric cancer complicated. In this review, we summarize the functions of E-cadherin and the signaling pathways it regulates. We aim to provide comprehensive perspectives in the molecular mechanism of E-cadherin and its involvement in gastric cancer initiation and progression. We also focus on its applications for early diagnosis, prognosis, and therapy in gastric cancer in order to open new avenues in this field. PMID:25184143

  19. Association of caveolin-1 genotypes with gastric cancer in Taiwan.

    PubMed

    Lin, Chih-Hsueh; Lin, Cheng-Chieh; Tsai, Chia-Wen; Chang, Wen-Shin; Yang, Chuan-Wei; Bau, Da-Tian

    2014-05-01

    Gastric cancer is one of the leading causes of tumor-related death worldwide, for which the prevalence and mortality rates are very high in developed countries. Caveolin-1 (Cav-1) is the main protein in the caveolin family and plays a role in tumorigenesis signaling. The contribution of CAV1 genetic variants to gastric cancer is still largely unknown. In the present study, we aimed to investigate the role of CAV1 genotypes in gastric cancer risk. We recruited 358 gastric patients and 358 cancer-free controls for CAV1 genotyping analysis. Six single-nucleotide polymorphisms (SNPs) of CAV1, C521A (rs1997623), G14713A (rs3807987), G21985A (12672038), T28608A (rs3757733), T29107A (rs7804372), and G32124A (rs3807992), were genotyped by the polymerase chain reaction-restriction fragment length polymorphism method. There was a significant difference between the gastric cancer and control groups in the genotypic frequency distribution of the CAV1 G14713A genotypes (p=1.24*10(-5)), with those carrying the A allele having a higher risk for gastric cancer compared to those with the GG genotype (p=0.0001). Our findings suggested that CAV1 genotype may determine the individual susceptibility to gastric cancer, and that the CAV1 G14713A genotype may serve as a novel biomarker for early detection and prediction of gastric cancer.

  20. Downregulated MicroRNA-133a in Gastric Juice as a Clinicopathological Biomarker for Gastric Cancer Screening.

    PubMed

    Shao, Juan; Fang, Peng-Hua; He, Biao; Guo, Li-Li; Shi, Ming-Yi; Zhu, Yan; Bo, Ping; Zhen-Wen, Zhen-Wen

    2016-01-01

    Circulatory miR-133a is a marker shared by several types of cancer. In this study we evaluated the feasibility of using miR-133a levels in gastric juice to screen for gastric cancer. A total of 204 samples of gastric juice and mucosa from gastric cancer, atrophic gastritis, gastric ulcer, superficial gastritis and healthy cases were collected by gastroscopy. The results showed that miR-133a levels in gastric juice and carcinoma tissues of patients with gastric cancer were significantly downregulated and positively correlated. Moreover, miR-133a in gastric juice has high operability, high reliability, high sensitivity, high specificity and relative stability, fit for clinical diagnosis of gastric cancer.

  1. Helicobacter pylori infection following partial gastrectomy for gastric cancer

    PubMed Central

    Park, Sanghoon; Chun, Hoon Jai

    2014-01-01

    Gastric remnants are an inevitable consequence of partial gastrectomy following resection for gastric cancer. The presence of gastric stumps is itself a risk factor for redevelopment of gastric cancer. Helicobacter pylori (H. pylori) infection is also a well-known characteristic of gastric carcinogenesis. H. pylori colonization in the remnant stomach therefore draws special interest from clinicians in terms of stomach cancer development and pathogenesis; however, the H. pylori-infected gastric remnant is quite different from the intact organ in several aspects and researchers have expressed conflicting opinions with respect to its role in pathogenesis. For instance, H. pylori infection of the gastric stump produced controversial results in several recent studies. The prevalence of H. pylori infection in the gastric stump has varied among recent reports. Gastritis developing in the remnant stomach presents with a unique pattern of inflammation that is different from the pattern seen in ordinary gastritis of the intact organ. Bile refluxate also has a significant influence on the colonization of the stomach stump, with several studies reporting mixed results as well. In contrast, the elimination of H. pylori from the gastric stump has shown a dramatic impact on eradication rate. H. pylori elimination is recognized to be important for cancer prevention and considerable agreement of opinion is seen among researchers. To overcome the current discrepancies in the literature regarding the role of H. pylori in the gastric stump, further research is required. PMID:24659869

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

    PubMed Central

    Poh, Ashleigh R; O'Donoghue, Robert J J

    2016-01-01

    Abstract 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

  3. 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

  4. Participation of microbiota in the development of gastric cancer.

    PubMed

    Wang, Li-Li; Yu, Xin-Juan; Zhan, Shu-Hui; Jia, Sheng-Jiao; Tian, Zi-Bin; Dong, Quan-Jiang

    2014-05-07

    There are a large number of bacteria inhabiting the human body, which provide benefits for the health. Alterations of microbiota participate in the pathogenesis of diseases. The gastric microbiota consists of bacteria from seven to eleven phyla, predominantly Proteobacteria, Firmicutes, Bacteroidetes, Actinobacteria and Fusobacteria. Intrusion by Helicobacter pylori (H. pylori) does not remarkably interrupt the composition and structure of the gastric microbiota. Absence of bacterial commensal from the stomach delays the onset of H. pylori-induced gastric cancer, while presence of artificial microbiota accelerates the carcinogenesis. Altered gastric microbiota may increase the production of N-nitroso compounds, promoting the development of gastric cancer. Further investigation of the carcinogenic mechanisms of microbiota would benefit for the prevention and management of gastric cancer.

  5. Association between serum vitamin D levels and gastric cancer: A retrospective chart analysis

    PubMed Central

    Vyas, Neil; Companioni, Rafael Ching; Tiba, Melik; Alkhawam, Hassan; Catalano, Carmine; Sogomonian, Robert; Baum, Joel; Walfish, Aaron

    2016-01-01

    AIM To determine whether there is an increased risk of gastric adenocarcinoma associated with vitamin D deficiency (VDd). METHODS A retrospective case control study was performed of all patients diagnosed with gastric adenocarcinoma between 2005 and 2015. After we excluded the patients without a documented vitamin D level, 49 patients were included in our study. RESULTS The average age of patients with gastric adenocarcinoma and documented vitamin D level was 64 years old (95%CI: 27-86) and average vitamin D level was 20.8 mg/dL (95%CI: 4-44). Compared to a matched control group, the prevalence of VDd/insufficiency in patients with gastric adenocarcinoma was significantly higher than normal vitamin D levels (83.7% vs 16.3%). Forty-one patients (83.7%) with adenocarcinoma showed VDd/insufficiency compared to 18 (37%) patients with normal vitamin D level without gastric cancer (OR: 8.8, 95%CI: 5-22, P value < 0.0001). The average age of males with gastric adenocarcinoma diagnosis was 60 years old vs 68 years old for females (P = 0.01). Stage II gastric adenocarcinoma was the most prevalent in our study (37%). CONCLUSION We reported a positive relationship between VDd and gastric adenocarcinoma, that is to say, patients with decreased VDd levels have an increased propensity for gastric adenocarcinoma. PMID:27672427

  6. Caspases and their role in gastric cancer.

    PubMed

    Frejlich, Ewelina; Rudno-Rudzińska, Julia; Janiszewski, Kacper; Salomon, Lukasz; Kotulski, Krzysztof; Pelzer, Oskar; Grzebieniak, Zygmunt; Tarnawa, Robert; Kielan, Wojciech

    2013-01-01

    Caspases (Cysteine Aspartate Specific Proteases) are a group of cysteine-containing proteolytic enzymes produced by the cells of living organisms. They participate in immunological functions, proliferation, cell migration and organization. Caspases also influence the secretion of various regulative factors. Moreover, they are responsible for cellular maturation and reconstruction, and for regulating the number and quality of cells initiating the apoptosis of old cells or those that cannot play their normal role due to abnormalities. Multiple pathological processes are associated with disorders in the activity of caspases. Changes in expression of individual caspases have been observed in gastric cancer. The expression of some caspases is also correlated with particular histological traits and the frequency of metastases, which suggests their possible use as a prognostic factor. It has also been discovered that some somatic mutations in caspase coding genes might lead to inhibition of apoptosis and the progression of the disease. Gene polymorphism may be a gastric cancer risk factor, but may also play a protective function. Considering the less than satisfactory effects of conventional therapeutic methods, the search for alternative ways to activate apoptosis - through gene therapy or selective activation of individual elements of the apoptotic pathways - constitutes a promising direction for studies of new therapeutic strategies. Caspases, enzymes playing a central role in the process of programmed cellular death, may possibly be a key to the development of a more effective anti-cancer therapy.

  7. MicroRNAs in gastric cancer metastasis.

    PubMed

    Shi, Zhaoqi; Wei, Qingxia; She, Junjun

    2014-01-01

    Gastric cancer (GC) is common worldwide and has a high rate of metastasis. The underlying molecular mechanism of metastasis are not entirely clear. MicroRNAs (miRNAs) are small, non-coding RNA molecules that regulate gene expression post-transcriptionally and are reported to be involved in multiple steps of tumor metastasis. Clarifying their roles in GC metastasis will improve understanding of this disease. Here, we review the involvement of miRNAs in multiple steps of GC metastasis, including epithelial-mesenchymal transitions, anoikis, angiogenesis, invasion, and migration. The clinical application of miRNAs as prognostic biomarkers in GC is also discussed.

  8. 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

  9. Urinary ADAM12 and MMP-9/NGAL complex detect the presence of gastric cancer.

    PubMed

    Shimura, Takaya; Dagher, Adelle; Sachdev, Monisha; Ebi, Masahide; Yamada, Tamaki; Yamada, Tomonori; Joh, Takashi; Moses, Marsha A

    2015-03-01

    Although the early diagnosis of gastric cancer provides the opportunity for curative endoscopic resection, comprehensive screening endoscopy would be invasive and expensive. To date, there is a complete absence of clinically useful gastric cancer biomarkers. With the goal of discovering noninvasive biomarkers for the early diagnosis of gastric cancer, we have conducted a case-control study using urine samples from individuals with gastric cancer versus healthy control samples. Of the enrolled 106 patients from September, 2012 to April, 2013, a cohort of 70 patients composed of 35 patients with gastric cancer and 35 age- and sex-matched healthy controls was analyzed. The gastric cancer group was composed of stage IA of 62.9% (22/35). The urinary levels of MMP-9/NGAL complex (uMMP-9/NGAL) and ADAM12 (uADAM12) were significantly higher in the gastric cancer group compared with the healthy control group as determined by monospecific ELISAs (uMMP-9/NGAL: median, 85 pg/mL vs. 0 pg/mL; P = 0.020; uADAM12: median, 3.35 ng/mL vs. 1.44 ng/mL; P < 0.001). Multivariate analysis demonstrated that both uMMP-9/NGAL and uADAM12 were significant, independent diagnostic biomarkers for gastric cancer. Moreover, MMP-9/NGAL activity was significantly elevated as determined by gelatin zymography. The combination of uMMP-9/NGAL with uADAM12 distinguished between control samples and gastric cancer samples with an AUC of 0.825 (P < 0.001) in an ROC analysis. Significantly, immunohistochemical analyses demonstrated a high coexpression of MMP-9 and NGAL (P < 0.001) and high expression of ADAM12 (P < 0.001) in gastric cancer tissues compared with adjacent normal tissues (N = 35). In summary, uMMP-9/NGAL and uADAM12 are potential noninvasive biomarkers for gastric cancer, including early-stage disease.

  10. 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

  11. Characteristics of gastric cancer in Asia.

    PubMed

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

    2014-04-28

    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.

  12. MG7 mimotope-based DNA vaccination for gastric cancer.

    PubMed

    Zhang, Dexin; Chen, Yu; Fan, Daiming

    2006-04-01

    Gastric cancer is still one of the leading causes of cancer-related death worldwide. Prevention and treatment of gastric cancer through vaccination has been difficult owing to lack of a specific target and poor immunity. A number of vaccination strategies have been used to augment immune responses against gastric cancer and some progress has been made. In a series of studies, the authors have focused on gastric cancer vaccination approaches based on MG7 mimotopes, which are mimicry epitopes selected from phage-displayed oligopeptide libraries with a gastric cancer cell-specific monoclonal antibody, MG7-Ab. Strategies employed in these studies include viral or plasmid vectors in combination with carrier sequence or unmethylated CpG with synthetic peptides in nanoemulsion. The results demonstrated that MG7 mimotopes could effectively and specifically induce both cellular and humoral immune reactions and in vivo antitumor responses. In particular, a four-MG7 mimotope DNA vaccine was found to elicit much stronger antitumor immune responses in mice compared with its single-mimotope counterpart. These encouraging findings might pave the way for the development of novel MG7 antigen-based vaccination approaches for human gastric cancer. The review also discusses other immune-enhancing vaccination strategies for gastric cancer.

  13. Screening for gastric cancer in Asia: current evidence and practice.

    PubMed

    Leung, Wai K; Wu, Ming-shiang; Kakugawa, Yasuo; Kim, Jae J; Yeoh, Khay-guan; Goh, Khean Lee; Wu, Kai-chun; Wu, Deng-chyang; Sollano, Jose; Kachintorn, Udom; Gotoda, Takuji; Lin, Jaw-town; You, Wei-cheng; Ng, Enders K W; Sung, Joseph J Y

    2008-03-01

    Gastric cancer is the second most common cause of death from cancer in Asia. Although surgery is the standard treatment for this disease, early detection and treatment is the only way to reduce mortality. This Review summarises the epidemiology of gastric cancer, and the evidence for, and current practices of, screening in Asia. Few Asian countries have implemented a national screening programme for gastric cancer; most have adopted opportunistic screening of high-risk individuals only. Although screening by endoscopy seems to be the most accurate method for detection of gastric cancer, the availability of endoscopic instruments and expertise for mass screening remains questionable--even in developed countries such as Japan. Therefore, barium studies or serum-pepsinogen testing are sometimes used as the initial screening tool in some countries, and patients with abnormal results are screened by endoscopy. Despite the strong link between infection with Helicobacter pylori and gastric cancer, more data are needed to define the role of its eradication in the prevention of gastric cancer in Asia. At present, there is a paucity of quality data from Asia to lend support for screening for gastric cancer.

  14. Coffee consumption and risk of gastric and pancreatic cancer--a prospective cohort study.

    PubMed

    Bidel, Siamak; Hu, Gang; Jousilahti, Pekka; Pukkala, Eero; Hakulinen, Timo; Tuomilehto, Jaakko

    2013-04-01

    Only few prospective studies have examined the association between coffee consumption and risk of gastric and pancreatic cancer. This study is designed to evaluate this relationship among Finns, whose coffee consumption is the highest in the world. A total of 60,041 Finnish men and women who were 26-74 years of age and without history of any cancer at baseline were included in the present analyses. Coffee consumption and other study parameters were determined at baseline using standardized measurements. Participants were prospectively followed up for onset of gastric and/or pancreatic cancer, emigration, death or until June 30, 2006. During a mean follow-up period of 18 years, 299 cases of gastric cancer and 235 cases of pancreatic cancer were found. There was a nonsignificant inverse association between coffee consumption and risk of gastric cancer among men but not in the women. The multivariate-adjusted hazard ratio of stomach and pancreatic cancer incidence for ≥ 10 cups of coffee per day compared with nondrinkers were 0.75 (95% CI, 0.40-1.41) (P for trend = 0.19) and 0.82 (95% CI, 0.38-1.76) (P for trend = 0.95) for the combined population of men and women, respectively. We did not find a significant association between coffee consumption and the risk of gastric and/or pancreatic cancers.

  15. Germline CDH1 deletions in hereditary diffuse gastric cancer families

    PubMed Central

    Oliveira, Carla; Senz, Janine; Kaurah, Pardeep; Pinheiro, Hugo; Sanges, Remo; Haegert, Anne; Corso, Giovanni; Schouten, Jan; Fitzgerald, Rebecca; Vogelsang, Holger; Keller, Gisela; Dwerryhouse, Sarah; Grimmer, Donna; Chin, Suet-Feung; Yang, Han-Kwang; Jackson, Charles E.; Seruca, Raquel; Roviello, Franco; Stupka, Elia; Caldas, Carlos; Huntsman, David

    2009-01-01

    Germline CDH1 point or small frameshift mutations can be identified in 30–50% of hereditary diffuse gastric cancer (HDGC) families. We hypothesized that CDH1 genomic rearrangements would be found in HDGC and identified 160 families with either two gastric cancers in first-degree relatives and with at least one diffuse gastric cancer (DGC) diagnosed before age 50, or three or more DGC in close relatives diagnosed at any age. Sixty-seven carried germline CDH1 point or small frameshift mutations. We screened germline DNA from the 93 mutation negative probands for large genomic rearrangements by Multiplex Ligation-Dependent Probe Amplification. Potential deletions were validated by RT–PCR and breakpoints cloned using a combination of oligo-CGH-arrays and long-range-PCR. In-silico analysis of the CDH1 locus was used to determine a potential mechanism for these rearrangements. Six of 93 (6.5%) previously described mutation negative HDGC probands, from low GC incidence populations (UK and North America), carried genomic deletions (UK and North America). Two families carried an identical deletion spanning 193 593 bp, encompassing the full CDH3 sequence and CDH1 exons 1 and 2. Other deletions affecting exons 1, 2, 15 and/or 16 were identified. The statistically significant over-representation of Alus around breakpoints indicates it as a likely mechanism for these deletions. When all mutations and deletions are considered, the overall frequency of CDH1 alterations in HDGC is ∼46% (73/160). CDH1 large deletions occur in 4% of HDGC families by mechanisms involving mainly non-allelic homologous recombination in Alu repeat sequences. As the finding of pathogenic CDH1 mutations is useful for management of HDGC families, screening for deletions should be offered to at-risk families. PMID:19168852

  16. 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

  17. Gastric pneumatosis in a small-for-gestational-age neonate.

    PubMed

    Penninga, Luit; Werz, Markus J; Reurings, Jurrian C; Nellensteijn, David R

    2015-08-03

    We describe a dysmature (small-for-gestational-age) neonate born at term with multiple congenital defects, who presented with bloody diarrhoea. The abdominal X-ray showed gastric pneumatosis. The patient was treated conservatively with intravenous fluids and antibiotics, and recovered uneventfully. The patient underwent genetic investigation, and was diagnosed with Cornelia de Lange syndrome. Gastric pneumatosis is rare, and may be the result of neonatal sepsis, gastritis, pyloric stenosis, necrotising enterocolitis of the stomach, misplacement of nasogastric tubes, or non-invasive positive pressure ventilation. Furthermore, it is speculated that gastric pneumatosis might more frequently occur with congenital, cardiac or genetic disorders.

  18. Radiation therapy for advanced gastric cancer

    SciTech Connect

    Tsukiyama, I.; Akine, Y.; Kajiura, Y.; Ogino, T.; Yamashita, K.; Egawa, S.; Hijikata, J.; Kitagawa, T.

    1988-07-01

    A retrospective study of 75 patients with advanced inoperable gastric cancers, referred to the National Cancer Center Hospital between 1962 and 1982, was performed. According to the Borrmann classification based on X ray findings, Type 1 was found in 3 patients, Type 2 in 5, Type 3 in 40, and Type 4 in 15. Twelve patients could not be classified. The histological type was papillary adenocarcinoma in 7 patients, tubular adenocarcinoma in 23, mucinous carcinoma in 6, poorly differentiated adenocarcinoma in 14, signet ring cell carcinoma in 12 and others in 13. The site of remote metastasis in 19 patients was Virchow's lymph node in 8 patients, Douglas pouch in 3, liver and lung in 2 each and others in 4. All patients were treated by a either telecobalt 60 unit or a linear accelerator using 6 Mv photon and the total dose to primary lesion was 4000 cGy in 5 weeks to 7000 cGy in 8-9 weeks. Complete response (CR) was achieved in 6 patients or 8.0%, partial response (PR) in 46 or 61.3%, and no change (NC) in 23 or 30.7%. The response rate based on the sum of CR and PR was about 70%. The 50% survival period in months was 26.5, 7.3, and 3.2, respectively for patients with CR, PR, and NC. For the response of advanced gastric cancer to chemotherapy in the National Cancer Center Hospital, the combined use of UFT and Mitomycin C gave the highest rate, 46%. As for as local response is concerned, the response rate to radiation was 70%, a better result than that of chemotherapy alone.

  19. Factors associated with early recurrence after curative surgery for gastric cancer

    PubMed Central

    Kang, Wei-Ming; Meng, Qing-Bin; Yu, Jian-Chun; Ma, Zhi-Qiang; Li, Zhi-Tian

    2015-01-01

    AIM: To characterize patterns of gastric cancer recurrence and patient survival and to identify predictors of early recurrence after surgery. METHODS: Clinicopathological data for 417 consecutive patients who underwent curative resection for gastric cancer were retrospectively analyzed. Tumor and node status was reclassified according to the 7th edition of the American Joint Committee on Cancer tumor-node-metastasis classification for carcinoma of the stomach. Survival data came from both the patients’ follow-up records and telephone follow-ups. Recurrent gastric cancer was diagnosed based on clinical imaging, gastroscopy with biopsy, and/or cytological examination of ascites, or intraoperative findings in patients who underwent reoperation. Predictors of early recurrence were compared in patients with pT1 and pT2-4a stage tumors. Pearson’s χ2 test and Fisher’s exact test were used to compare differences between categorical variables. Survival curves were constructed using the Kaplan-Meier method and compared via the log-rank test. Variables identified as potentially important for early recurrence using univariate analysis were determined by multivariate logistic regression analysis. RESULTS: Of 417 gastric cancer patients, 80 (19.2%) were diagnosed with early gastric cancer and the remaining 337 (80.8%) were diagnosed with locally advanced gastric cancer. After a median follow-up period of 56 mo, 194 patients (46.5%) experienced recurrence. The mean time from curative surgery to recurrence in these 194 patients was 24 ± 18 mo (range, 1-84 mo). Additionally, of these 194 patients, 129 (66.5%) experienced recurrence within 2 years after surgery. There was no significant difference in recurrence patterns between early and late recurrence (P < 0.05 each). For pT1 stage gastric cancer, tumor size (P = 0.011) and pN stage (P = 0.048) were associated with early recurrence of gastric tumors. Patient age, pT stage, pN stage, Lauren histotype, lymphovascular

  20. [Early diagnosis of gastric cancer, a utopian idea? (author's transl)].

    PubMed

    Seifert, E

    1981-05-01

    In order to improve the prognosis of gastric cancer it is necessary to discover the lesions at an early stage of the disease. Early gastric cancer has an excellent prognosis with a postoperative survival rate of 77 to 99%. Since 1970 we have diagnosed 76 cases of early gastric cancer and the percentage of early cancer out of all gastric cancers increased from 10 to 23%. This improvement is based on selected examinations of high-risk patients, on better diagnostic methods and on our better knowledge of macroscopic and histological appearance. In particular, the use of snare biopsy in protruding lesions and the implementation of continuous endoscopic-bioptic follow-up of all gastric ulcers until complete healing is achieved have improved the accuracy of histological verification. In 16 out of 76 cases of early gastric cancer a multicentric growth was observed. The diagnosis of gastric cancer at an early stage is not an utopian idea. It is reality when we pay attention to the aspects mentioned before.

  1. CA125 is a potential biomarker to predict surgically incurable gastric and cardia cancer

    PubMed Central

    Luo, Taobo; Chen, Wenhu; Wang, Lifang; Zhao, Hongguang

    2016-01-01

    Abstract Preoperative evaluation of the curability of gastric and cardia cancer is important to avoid risks of unnecessary surgery. Our previous study has reported several clinical parameters associated with incurable gastric surgery. In this study, we aimed to evaluate the correlation between CA125 and the curability of gastric and cardia cancer. A total of 297 cases of gastric and cardia cancer were analyzed retrospectively, including 153 cases with radical surgery and 144 with surgery for incurable gastric or cardia cancer. χ2 test was performed to analyze the associations between curability or incurable factors and clinicopathological data, including CA125 value. ROC curves were generated, and cutoff points for curability, T status, N status, peritoneal metastasis, and distant metastasis were found, respectively. Binary logistic regression was performed to verify the associations between dependent variables (curability, T status, N status, peritoneal metastasis, and distant metastasis) and covariates (related clinicopathological data from step 1 and cutoff points from step 2). Esophageal involvement, T grade, and CA125 were risk factors of curability. T grade and Borrmann type were risk factors of T status. T grade and CA125 were risk factors of N status. Age, esophageal involvement, T grade, and CA125 were risk factors of peritoneal metastasis. CA125 was risk factor of distant metastasis. CA125 is a potential biological marker for curability prediction of gastric and cardia cancer. PMID:28002320

  2. Dual Roles of Gastric Gland Mucin-specific O-glycans in Prevention of Gastric Cancer

    PubMed Central

    Nakayama, Jun

    2014-01-01

    Gastric gland mucin is secreted from gland mucous cells, including pyloric gland cells and mucous neck cells located in the lower layer of the gastric mucosa. These mucins typically contain O-glycans carrying terminal α1,4-linked N-acetylglucosamine residues (αGlcNAc) attached to the scaffold protein MUC6, and biosynthesis of the O-glycans is catalyzed by the glycosyltransferase, α1,4-N-acetylglucosaminyltransferase (α4GnT). We previously used expression cloning to isolate cDNA encoding α4GnT, and then demonstrated that αGlcNAc functions as natural antibiotic against Helicobacter pylori, a microbe causing various gastric diseases including gastric cancer. More recently, it was shown that αGlcNAc serves as a tumor suppressor for differentiated-type adenocarcinoma. This review summarizes these findings and identifies dual roles for αGlcNAc in gastric cancer. PMID:24761044

  3. Epidemio-hygieological aspects of gastric neoplasms in aged patients.

    PubMed

    Shibata, H; Hara, M; Makino, T; Kikuchi, K; Senoue, I; Nomiyama, T; Miwa, M; Suzuki, S; Harasawa, S; Tani, N; Miwa, T

    1982-07-01

    A 100-year-old male who died of gastric carcinoma was discussed and illustrated epidemiohygieologically. According to dynamic population statistics of the Health and Welfare Ministry of Japan, 418 persons over the age of 100 years died in 1979. Among them, 157 (38%) died of cardiovascular diseases and 49 (12%) died of pulmonary diseases, but only six died of neoplasms including two with gastric carcinomas (0.48%). To our knowledge no such case has been reported previously in the literature.

  4. Upregulation of plasma C9 protein in gastric cancer patients

    PubMed Central

    Chong, Poh-Kuan; Lee, Huiyin; Loh, Marie Chiew Shia; Choong, Lee-Yee; Lin, Qingsong; So, Jimmy Bok Yan; Lim, Khong Hee; Soo, Ross Andrew; Yong, Wei Peng; Chan, Siew Pang; Smoot, Duane T.; Ashktorab, Hassan; Yeoh, Khay Guan; Lim, Yoon Pin

    2013-01-01

    Gastric cancer is one of the leading causes of cancer-related deaths worldwide. Current biomarkers used in the clinic do not have sufficient sensitivity for gastric cancer detection. To discover new and better biomarkers, protein profiling on plasma samples from 25 normal, 15 early-stage and 21 late-stage cancer was performed using an iTRAQ-LC-MS/MS approach. The level of C9 protein was found to be significantly higher in gastric cancer compared with normal subjects. Immunoblotting data revealed a congruent trend with iTRAQ results. The discriminatory power of C9 between normal and cancer states was not due to inter-patient variations and was independent from gastritis and Helicobacter pylori status of the patients. C9 overexpression could also be detected in a panel of gastric cancer cell lines and their conditioned media compared with normal cells, implying that higher C9 levels in plasma of cancer patients could be attributed to the presence of gastric tumor. A subsequent blind test study on a total of 119 plasma samples showed that the sensitivity of C9 could be as high as 90% at a specificity of 74%. Hence, C9 is a potentially useful biomarker for gastric cancer detection. PMID:20707004

  5. 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.

  6. 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

  7. Screening and Early Detection of Gastric Cancer: East Versus West.

    PubMed

    Suh, Yun-Suhk; Yang, Han-Kwang

    2015-10-01

    Low ratio of mortality over incidence of gastric cancer in Asian countries including Korea and Japan could be explained by early detection after screening, different treatment strategy, or genetic disparity between the East and West. Early detection after screening program for gastric cancer and subsequent surgical treatment including appropriate lymph node dissection has been developed successfully in high risk areas such as East Asian countries. Even in countries with a low prevalence of gastric cancer, a specific screening program is recommended for any high-risk population.

  8. 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

  9. Preoperative staging of nodal status in gastric cancer

    PubMed Central

    Berlth, Felix; Chon, Seung-Hun; Chevallay, Mickael; Jung, Minoa Karin

    2017-01-01

    An accurate preoperative staging of nodal status is crucial in gastric cancer, because it has a great impact on prognosis and therapeutic decision-making. Different staging methods have been evaluated for gastric cancer in order to predict nodal involvement. So far, no technique could meet the necessary requirements, which include a high detection rate of infiltrated lymph nodes and a low frequency of false-positive results. This article summarizes different staging methods used to assess lymph node status in patients with gastric cancer, evaluates the evidence, and proposes to establish new methods. PMID:28217758

  10. Comparison of "early gastric cancer" in Britain and Japan.

    PubMed Central

    Evans, D M; Craven, J L; Murphy, F; Cleary, B K

    1978-01-01

    Before the introduction of endoscopy, four out of 720 cases of gastric cancer were diagnosed before the cancer had breached the muscularis propia, an incidence of 0.5%. Using endoscopy and endoscopic biopsy, 10 out of 101 cases of gastric cancer were diagnosed at this "early" stage, an incidence of 10%. Their clinical, morphological, and histological characteristics are compared with those of Japanese "early gastric cancers" and reveal a remarkable similarity. The results of this study suggest that a higher proportion of British gastric cancers could be diagnosed at an "early" stage by more intensive investigation of dyspeptic patients using up to date radiological techniques, fibreoptic endoscopy, and endoscopic biopsy. Images Fig. 1 Fig. 2 Fig. 3 Fig. 5 Fig. 6 Fig. 8 PMID:624498

  11. Gastric Metastasis of Breast Cancer: A Case Series.

    PubMed

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

    2016-09-05

    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.

  12. [Gastric cancer screening in Japan, now and tomorrow].

    PubMed

    Nakajima, Shigemi

    2012-10-01

    The screening rate of gastric cancer in the population surveyed by Japanese government was 34.3% in 2010. The rates differed by medical insurance holders: 60-70% in the big-company insurances; 32% in the national government-assisted small-company insurances; 10% in the local government-assisted non-company individual insurances and the dependents of any insurance holders. The only method of gastric cancer mass screening that Japanese government approves now is sodium bicarbonate-barium X-ray examination. The rate diagnosed as gastric cancer in the system was 0.088% in 2009. A new strategy using serum tests for pepsinogens and Helicobacter pylori-antibody has been proposed. Test and eradication may be the best method for screening high-risk subjects and primary prevention of gastric cancer, and the subsequent cancer screening.

  13. Helicobacter pylori eradication as a preventive tool against gastric cancer.

    PubMed

    Hamajima, Nobuyuki; Goto, Yasuyuki; Nishio, Kazuko; Tanaka, Daisuke; Kawai, Sayo; Sakakibara, Hisataka; Kondo, Takaaki

    2004-01-01

    Helicobacter pylori (H. pylori), which increases the risk of gastric diseases, including digestive ulcers and gastric cancer, is highly prevalent in Asian countries. There is no doubt that eradication of the bacterium is effective as a treatment of digestive ulcer, but eradication aiming to reduce the gastric cancer risk is still controversial. Observational studies in Japan demonstrated that the eradication decreased the gastric cancer risk among 132 stomach cancer patients undergoing endoscopical resection (65 treated with omeprazol and antibiotics and 67 untreated). In Columbia, 976 participants were randomized into eight groups in a three-treatment factorial design including H. pylori eradication, resulting in significant regression in the H. pylori eradication group. A recent randomized study in China also showed a significant reduction of gastric cancer risk among those without any gastric atrophy, intestinal metaplasia, and dysplasia. Efficacy of eradication may vary in extent among countries with different incidence rates of gastric cancer. Since the lifetime cumulative risk (0 to 84 years old) of gastric cancer in Japan is reported to be 12.7% for males and 4.8% for females (Inoue and Tominaga, 2003), the corresponding values for H. pylori infected Japanese can be estimated at 21.2% in males and 8.0% in females under the assumptions that the relative risk for infected relative to uninfected is 5 and the proportion of those infected is 0.5. Both the fact that not all individuals are infected among those exposed and the knowledge that only a small percentage of individuals infected with the bacterium develop gastric cancer, indicate the importance of gene-environment interactions. Studies on such interactions should provide useful information for anti-H. pylori preventive strategies.

  14. Metastatic gastric cancer to the female genital tract

    PubMed Central

    Matsushita, Hiroshi; Watanabe, Kazushi; Wakatsuki, Akihiko

    2016-01-01

    Metastases to the female genital tract from gastric cancer are rare, but they significantly worsen the prognosis of such patients. The potential routes for metastasis to the female genital tract from gastric cancer include hematogenous spread, lymphatic spread and surface implantation. The rate of lymphatic metastasis to the ovary from gastric cancer has been reported to be higher compared with that from colorectal cancer. Uterine or Fallopian tube metastases are usually secondary to ovarian metastases, which are typically identified prior to the detection of gastric cancer in half of all synchronous cases, with complaints of abdominal distention, pain, palpable mass, or abnormal uterine bleeding. The prognosis of patients with female genital tract metastases from gastric cancer is extremely poor, and is worse compared with that of other primary sites, such as the breast and colorectum. In the past, surgical intervention in such patients consisted mainly of palliative resection to relieve the symptoms associated with a sizeable pelvic mass. However, recent retrospective studies based on a relatively small number of patients have reported that surgical tumor debulking plus chemotherapy may improve the prognosis of patients with metastatic ovarian cancer originating from gastric cancer. PMID:27882232

  15. [Aging and gynecologic cancer].

    PubMed

    Arrighi, Arturo A

    2005-01-01

    The interrelation between cancer and ageing in women is emphasized, on its increased incidence, in their molecular background, into the particular biological characteristics of the different tumors and the effects of ageing in the affected women.

  16. 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

  17. 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

  18. 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

  19. Prolyl hydroxylase 3 inhibited the tumorigenecity of gastric cancer cells.

    PubMed

    Cui, Lei; Qu, Jianguo; Dang, Shengchun; Mao, Zhengfa; Wang, Xuqing; Fan, Xin; Sun, Kang; Zhang, Jianxin

    2014-09-01

    Gastric cancer is one of the most common malignancies and the second leading cause of cancer-related death in the world, and it is very urgent to develop novel therapeutic strategies. Although HIF-1α is the most highly characterized target of prolyl hydroxylase 3 (PHD3), PHD3 has been shown to regulate several signal pathways independent of HIF-1α. Here, we found that the expression of PHD3 was decreased in the clinical gastric cancer samples and reversely correlated with tumor size and tumor stage. Over-expression of PHD3 in the gastric cancer cells significantly inhibited cell growth in vitro and in vivo, while knockdown the expression of PHD3 promoted the tumorigenecity of gastric cancer cells. Mechanistically, it showed that PHD3 downregulated the expression of beta-catenin and inhibited beta-catenin/T-cell factor (TCF) signaling. Taken together, our findings demonstrate that PHD3 inhibits gastric cancer by suppressing the beta-catenin/TCF signaling and PHD3 might be an important therapeutic target in gastric cancer.

  20. Recurrent candidiasis and early-onset gastric cancer in a patient with a genetically defined partial MYD88 defect.

    PubMed

    Vogelaar, Ingrid P; Ligtenberg, Marjolijn J L; van der Post, Rachel S; de Voer, Richarda M; Kets, C Marleen; Jansen, Trees J G; Jacobs, Liesbeth; Schreibelt, Gerty; de Vries, I Jolanda M; Netea, Mihai G; Hoogerbrugge, Nicoline

    2016-04-01

    Gastric cancer is caused by both genetic and environmental factors. A woman who suffered from recurrent candidiasis throughout her life developed diffuse-type gastric cancer at the age of 23 years. Using whole-exome sequencing we identified a germline homozygous missense variant in MYD88. Immunological assays on peripheral blood mononuclear cells revealed an impaired immune response upon stimulation with Candida albicans, characterized by a defective production of the cytokine interleukin-17. Our data suggest that a genetic defect in MYD88 results in an impaired immune response and may increase gastric cancer risk.

  1. Helicobacter pylori Infection and Risk of Gastric Cancer in Korea: A Quantitative Systematic Review

    PubMed Central

    2016-01-01

    Objectives: In the context of the global decrease in mortality due to gastric cancer, previous studies have reported that the effect of chronic Helicobacter pylori (H. pylori) infection on the incidence of gastric cancer varies among regions. This systematic review was conducted to investigate H. pylori as a risk factor for gastric cancer in Korea, where the incidence of gastric cancer is among the highest in the world. Methods: A search strategy was established to identify articles published in Korean as well as in English. Ultimately, we included observational studies conducted among Korean patients that designed with an age-matched and sex-matched control group that reported the odds ratio associated with H. pylori. Gastric cancer cases were subdivided into overall (OGC), cardia (CGC), non-cardia (NGC), early (EGC), advanced, intestinal (IGC), and diffuse forms of gastric cancer. Summary odds ratios (SORs) with 95% confidence intervals (CIs) were calculated in the meta-analysis using a random-effect model. Results: Eleven case-control studies were ultimately selected. H. pylori was associated with an SOR of 1.81 (95% CI, 1.29 to 2.54) for OGC. Additionally, statistically significant risks were observed for CGC, NGC, EGC, and IGC. Conclusions: Chronic H. pylori infection was found to raise the risk of gastric cancer among Koreans, with the highest risk observed for CGC and EGC (SOR=2.88 for both). Follow-up clinical epidemiologic studies are needed to assess the effects of current treatments aimed at eradicating H. pylori infections. PMID:27499162

  2. Epigenetically downregulated Semaphorin 3E contributes to gastric cancer

    PubMed Central

    Chen, Hui; Xie, Guo-Hua; Wang, Wei-Wei; Yuan, Xiang-Liang; Xing, Wen-Ming; Liu, Hong-Jing; Chen, Jin; Dou, Min; Shen, Li-Song

    2015-01-01

    Axon guidance protein Semaphorin 3E (Sema3E) promotes tumor metastasis and suppresses tumor cell death. Here, we demonstrated that Sema3E was decreased in gastric cancer. Its levels were inversely associated with tumor progression. Levels of Sema3E were associated with low p300 and high class I histone deacetylase (class I HDAC). Ectopic expression of Sema3E inhibited proliferation and colony formation of gastric cancer cell lines in vitro and xenografts in vivo. Sema3E overexpression inhibited migration and invasion of gastric cancer cells, which was associated with induction of E-cadherin and reduction of Akt and ERK1/2 phosphorylation. We suggest that silencing of Sema3E contributes to the pathogenesis of gastric cancer. PMID:26036259

  3. Laparoscopic gastric surgery for cancer: where do we stand?

    PubMed

    Antonakis, Pantelis T; Ashrafian, Hutan; Isla, Alberto Martinez

    2014-10-21

    Gastric cancer poses a significant public health problem, especially in the Far East, due to its high incidence in these areas. Surgical treatment and guidelines have been markedly different in the West, but nowadays this debate is apparently coming to an end. Laparoscopic surgery has been employed in the surgical treatment of gastric cancer for two decades now, but with controversies about the extent of resection and lymphadenectomy. Despite these difficulties, the apparent advantages of the laparoscopic approach helped its implementation in early stage and distal gastric cancer, with an increase on the uptake for distal gastrectomy for more advanced disease and total gastrectomy. Nevertheless, there is no conclusive evidence about the laparoscopic approach yet. In this review article we present and analyse the current status of laparoscopic surgery in the treatment of gastric cancer.

  4. 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

  5. [Enzymes in gastric juice. An aid in the diagnosis of gastric cancer].

    PubMed

    Marino Alarcón, O; Concho Lugo, H; Silva Larralte, T; Tauil Bsereni, E; Solano Nava, P; Machado, D; Chacón Patiño, A

    1996-01-01

    In the present study we measured the activities of the following enzymes: LDH (lactic dehydrogenase), beta-glucuronidase, acid maltase, phosphohexoseisomerase (PHI) and acid proteases in the gastric juice of patients with gastric cancer (n = 50) (Case Group), in endoscopically normal subjects (n = 50) and in subjects with different non tumor-like digestive pathologies (n = 55) (Control Groups). In the patients with gastric carcinoma we found a significant increase in LDH, beta-glucuronidase, PHI and acid maltase activities and a decreased activity of acid proteases. The results agree with previous findings from other workers. The variations of enzyme activities in gastric juice can help to differentiate between malignant and benign processes of the gastric mucosa.

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

    PubMed

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

    2014-10-01

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

  7. Host pathogen interactions in Helicobacter pylori related gastric cancer.

    PubMed

    Chmiela, Magdalena; Karwowska, Zuzanna; Gonciarz, Weronika; Allushi, Bujana; Stączek, Paweł

    2017-03-07

    Helicobacter pylori (H. pylori), discovered in 1982, is a microaerophilic, spiral-shaped gram-negative bacterium that is able to colonize the human stomach. Nearly half of the world's population is infected by this pathogen. Its ability to induce gastritis, peptic ulcers, gastric cancer and mucosa-associated lymphoid tissue lymphoma has been confirmed. The susceptibility of an individual to these clinical outcomes is multifactorial and depends on H. pylori virulence, environmental factors, the genetic susceptibility of the host and the reactivity of the host immune system. Despite the host immune response, H. pylori infection can be difficult to eradicate. H. pylori is categorized as a group I carcinogen since this bacterium is responsible for the highest rate of cancer-related deaths worldwide. Early detection of cancer can be lifesaving. The 5-year survival rate for gastric cancer patients diagnosed in the early stages is nearly 90%. Gastric cancer is asymptomatic in the early stages but always progresses over time and begins to cause symptoms when untreated. In 97% of stomach cancer cases, cancer cells metastasize to other organs. H. pylori infection is responsible for nearly 60% of the intestinal-type gastric cancer cases but also influences the development of diffuse gastric cancer. The host genetic susceptibility depends on polymorphisms of genes involved in H. pylori-related inflammation and the cytokine response of gastric epithelial and immune cells. H. pylori strains differ in their ability to induce a deleterious inflammatory response. H. pylori-driven cytokines accelerate the inflammatory response and promote malignancy. Chronic H. pylori infection induces genetic instability in gastric epithelial cells and affects the DNA damage repair systems. Therefore, H. pylori infection should always be considered a pro-cancerous factor.

  8. Host pathogen interactions in Helicobacter pylori related gastric cancer

    PubMed Central

    Chmiela, Magdalena; Karwowska, Zuzanna; Gonciarz, Weronika; Allushi, Bujana; Stączek, Paweł

    2017-01-01

    Helicobacter pylori (H. pylori), discovered in 1982, is a microaerophilic, spiral-shaped gram-negative bacterium that is able to colonize the human stomach. Nearly half of the world's population is infected by this pathogen. Its ability to induce gastritis, peptic ulcers, gastric cancer and mucosa-associated lymphoid tissue lymphoma has been confirmed. The susceptibility of an individual to these clinical outcomes is multifactorial and depends on H. pylori virulence, environmental factors, the genetic susceptibility of the host and the reactivity of the host immune system. Despite the host immune response, H. pylori infection can be difficult to eradicate. H. pylori is categorized as a group I carcinogen since this bacterium is responsible for the highest rate of cancer-related deaths worldwide. Early detection of cancer can be lifesaving. The 5-year survival rate for gastric cancer patients diagnosed in the early stages is nearly 90%. Gastric cancer is asymptomatic in the early stages but always progresses over time and begins to cause symptoms when untreated. In 97% of stomach cancer cases, cancer cells metastasize to other organs. H. pylori infection is responsible for nearly 60% of the intestinal-type gastric cancer cases but also influences the development of diffuse gastric cancer. The host genetic susceptibility depends on polymorphisms of genes involved in H. pylori-related inflammation and the cytokine response of gastric epithelial and immune cells. H. pylori strains differ in their ability to induce a deleterious inflammatory response. H. pylori-driven cytokines accelerate the inflammatory response and promote malignancy. Chronic H. pylori infection induces genetic instability in gastric epithelial cells and affects the DNA damage repair systems. Therefore, H. pylori infection should always be considered a pro-cancerous factor. PMID:28321154

  9. Therapeutic mechanism of ginkgo biloba exocarp polysaccharides on gastric cancer

    PubMed Central

    Xu, Ai-Hua; Chen, Hua-Sheng; Sun, Bu-Chan; Xiang, Xiao-Ren; Chu, Yun-Fei; Zhai, Fan; Jia, Ling-Chang

    2003-01-01

    AIM: To study the therapeutic mechanism of Ginkgo biloba exocarp polysaccharides (GBEP) on gastric cancer. METHODS: Thirty patients with gastric cancer were treated with oral GBEP capsules. The area of tumors was measured by electron gastroscope before and after treatment, then the inhibitory and effective rates were calculated. The ultrastructures of tumor cells were examined by transmissional electron microscope. Cell culture, MTT, flow cytometry were performed to observe proliferation, apoptosis and changes of relevant gene expression of human gastric cancer SGC-7901 cells. RESULTS: Compared with the statement before treatment, GBEP capsules could reduce the area of tumors, and the effective rate was 73.4%. Ultrastructural changes of the cells indicated that GBEP could induce apoptosis and differentiation in tumor cells of patients with gastric cancer. GBEP could inhibit the growth of human gastric cancer SGC-7901 cells following 24-72 h treatment in vitro at 10-320 mg/L, which was dose- and time-dependent. GBEP was able to elevate the apoptosis rate and expression of c-fos gene, but reduce the expression of c-myc and bcl-2 genes also in a dose-dependent manner. CONCLUSION: The therapeutic mechanism of GBEP on human gastric cancer may relate to its effects on the expression of c-myc, bcl-2 and c-fos genes, which can inhibit proliferation and induce apoptosis and differentiation of tumor cells. PMID:14606069

  10. Robot-assisted laparoscopic gastrectomy for gastric cancer

    PubMed Central

    Caruso, Stefano; Franceschini, Franco; Patriti, Alberto; Roviello, Franco; Annecchiarico, Mario; Ceccarelli, Graziano; Coratti, Andrea

    2017-01-01

    Phase III evidence in the shape of a series of randomized controlled trials and meta-analyses has shown that laparoscopic gastrectomy is safe and gives better short-term results with respect to the traditional open technique for early-stage gastric cancer. In fact, in the East laparoscopic gastrectomy has become routine for early-stage gastric cancer. In contrast, the treatment of advanced gastric cancer through a minimally invasive way is still a debated issue, mostly due to worries about its oncological efficacy and the difficulty of carrying out an extended lymphadenectomy and intestinal reconstruction after total gastrectomy laparoscopically. Over the last ten years the introduction of robotic surgery has implied overcoming some intrinsic drawbacks found to be present in the conventional laparoscopic procedure. Robot-assisted gastrectomy with D2 lymphadenectomy has been shown to be safe and feasible for the treatment of gastric cancer patients. But unfortunately, most available studies investigating the robotic gastrectomy for gastric cancer compared to laparoscopic and open technique are so far retrospective and there have not been phase III trials. In the present review we looked at scientific evidence available today regarding the new high-tech surgical robotic approach, and we attempted to bring to light the real advantages of robot-assisted gastrectomy compared to the traditional laparoscopic and open technique for the treatment of gastric cancer. PMID:28101302

  11. Alcohol Consumption and Gastric Cancer Risk: A Meta-Analysis

    PubMed Central

    Ma, Ke; Baloch, Zulqarnain; He, Ting-Ting; Xia, Xueshan

    2017-01-01

    Background We sought to determine by meta-analysis the relationship between drinking alcohol and the risk of gastric cancer. Material/Methods A systematic Medline search was performed to identify all published reports of drinking alcohol and the associated risk of gastric cancer. Initially we retrieved 2,494 studies, but after applying inclusion and exclusion criteria, only ten studies were found to be eligible for our meta-analysis. Results Our meta-analysis showed that alcohol consumption elevated the risk of gastric cancer with an odds ratio (OR) of 1.39 (95% CI 1.20–1.61). Additionally, subgroup analysis showed that only a nested case-control report from Sweden did not support this observation. Subgroup analysis of moderate drinking and heavy drinking also confirmed that drinking alcohol increased the risk of gastric cancer. Publication bias analysis (Begg’s and Egger’s tests) showed p values were more than 0.05, suggesting that the 10 articles included in our analysis did not have a publication bias. Conclusions The results from this meta-analysis support the hypothesis that alcohol consumption can increase the risk of gastric cancer; suggesting that effective moderation of alcohol drinking may reduce the risk of gastric cancer. PMID:28087989

  12. Prevention strategies for gastric cancer: a global perspective.

    PubMed

    Park, Jin Young; von Karsa, Lawrence; Herrero, Rolando

    2014-11-01

    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.

  13. Clinicopathological features and surgical safety of gastric cancer in elderly patients.

    PubMed

    Lim, Joo Hyun; Lee, Dong Ho; Shin, Cheol Min; Kim, Nayoung; Park, Young Soo; Jung, Hyun Chae; Song, In Sung

    2014-12-01

    Gastric cancer is one of the most common cancers, especially among the elderly. However little is known about gastric cancer in elderly patients. This study was designed to evaluate the specific features of gastric cancer in elderly patients. Medical records of 1,107 patients who had radical gastrectomy for gastric cancer between June 2005 and December 2009 were reviewed. They were divided into young (<65 yr, n=676), young-old (65-74 yr, n=332), and old-old age group (≥75 yr, n=99). Increased CA 19-9 (5.6%, 13.4%, 14.6%, P=0.001), advanced diseases (42.5%, 47.0%, and 57.6, P=0.014), and node metastasis (37.6%, 38.9%, 51.5%, P=0.029) were more common in the young-old and old-old age groups. There were no significant differences in Helicobacter pylori status (63.6%, 56.7%, 61.2%, P=0.324) between the three groups. Surgery-related complication rates were similar in the three groups (5.3%, 5.1%, 8.1%, P=0.497). Microsatellite instability (P<0.001) and p53 overexpression (P<0.001) were more common among the elderly. The elderly group had more synchronous tumors (7.5%, 10.2%, 17.2%; P=0.006). Surgery can be applied to elderly gastric cancer without significant risk of complications. However, considering the more advanced disease and synchronous tumors among the elderly, care should be taken while deciding the extent of surgery for elderly gastric cancer.

  14. Increase in Endoscopic and Laparoscopic Surgery Regarding the Therapeutic Approach of Gastric Cancer Detected by Cancer Screening in Saga Prefecture, Japan.

    PubMed

    Yamaguchi, Shunsuke; Sakata, Yasuhisa; Iwakiri, Ryuichi; Hara, Megumi; Akutagawa, Kayo; Shimoda, Ryo; Yamaguchi, Daisuke; Hidaka, Hidenori; Sakata, Hiroyuki; Fujimoto, Kazuma; Mizuguchi, Masanobu; Shimoda, Yuichiro; Irie, Hiroyuki; Noshiro, Hirokazu

    2016-01-01

    Objective Despite recent advances in endoscopic treatment and laparoscopic surgery for gastric cancers, an increase in the uptake of these therapeutic approaches has not yet been fully demonstrated. Therefore, the present study aimed to investigate the change in therapeutic approaches regarding the treatment of gastric cancers detected by cancer screening in Saga Prefecture, Japan between April 2002 and March 2011. Methods Gastric cancer screening by X-ray was performed on 311,074 subjects between April 2002 and March 2011. In total, 534 patients were thereafter diagnosed with gastric cancer. Eighteen subjects were excluded because precise details of their treatment were not available. To evaluate the changes in the therapeutic approach, the observation period was divided into three 3-year intervals: Period I: April 2002 to March 2005; Period II: April 2005 to March 2008; Period III: April 2008 to March 2011. Results The use of open laparotomy for the treatment of gastric cancer decreased, and laparoscopic surgery and endoscopic treatment increased markedly in a time-dependent manner. A 2.5-fold increase in endoscopic treatment, and a 18.4-fold increase in laparoscopic surgery were observed in Period III compared with Period I (after adjusting for age and tumor characteristics). Conclusion Endoscopic treatment and laparoscopic surgery for gastric cancer increased during the investigation period (2002-2011), although the tumor characteristics of the gastric cancers detected through cancer screening in Saga Prefecture, Japan did not show any changes.

  15. [Present and future state of cancer screening for esophageal cancer and gastric cancer].

    PubMed

    Nakashima, Hirotaka; Nagahama, Ryuji; Yoshida, Misao

    2012-01-01

    Recently, endoscopic examinations have played a major role in the diagnosis and treatment in the field of gastroenterology. It is considered that endoscopy would be an important examination for cancer screening of the esophagus and the stomach. However, endoscopic services for cancer screening are in short supply. Furthermore, we have to take the complications and poor economic benefits of endoscopy in to consideration when we apply it as a practical cancer screening system. Thus, an effective primary screening system must be provided for the endoscopic screening of cancer of the esophagus and the stomach. People with a defect in aldehyde dehydrogenase-2(ALDH2)should be distinguished by their facial flushing in drinking and for their high risks of esophageal cancer. In cases with gastric cancer screening by endoscopy, an x-ray study is expected to be a primary screening because of its efficacy. It already has been recommended for population-based screening in Japanese guidelines for gastric cancer screening. In cases with opportunistic screening of gastric cancer, patients should be allowed to choose from several studies such as the x-ray study, direct endoscopy, and the so-called high risk screening of gastric cancer for estimating risks and planning of screening for gastric cancer.

  16. 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

  17. Hereditary diffuse gastric cancer: implications of genetic testing for screening and prophylactic surgery.

    PubMed

    Cisco, Robin M; Ford, James M; Norton, Jeffrey A

    2008-10-01

    Approximately 10% of patients with gastric cancer show familial clustering, and 3% show autosomal dominance and high penetrance. Hereditary diffuse gastric cancer (HDGC) is an autosomal-dominant, inherited cancer syndrome in which affected individuals develop diffuse-type gastric cancer at a young age. Inactivating mutations in the E-cadherin gene CDH1 have been identified in 30% to 50% of patients. CDH1 mutation carriers have an approximately 70% lifetime risk of developing DGC, and affected women carry an additional 20% to 40% risk of developing lobular breast cancer. Because endoscopic surveillance is ineffective in identifying early HDGC, gene-directed prophylactic total gastrectomy currently is offered for CDH1 mutation carriers. In series of asymptomatic individuals undergoing total gastrectomy for CDH1 mutations, the removed stomachs usually contain small foci of early DGC, making surgery not prophylactic but curative. The authors of this review recommend consideration of total gastrectomy in CDH1 mutation carriers at an age 5 years younger than the youngest family member who developed gastric cancer. Individuals who choose not to undergo prophylactic gastrectomy should be followed with biannual chromoendoscopy, and women with CDH1 mutations also should undergo regular surveillance with magnetic resonance imaging studies of the breast. Because of the emergence of gene-directed gastrectomy for HDGC, today, a previously lethal disease is detected by molecular techniques, allowing curative surgery at an early stage.

  18. Expression of NUAK2 in gastric cancer tissue and its effects on the proliferation of gastric cancer cells

    PubMed Central

    Tang, Lin; Tong, Shu-Juan; Zhan, Zhen; Wang, Qian; Tian, Yuan; Chen, Feng

    2017-01-01

    The present study aimed to analyze the expression and effects of NUAK2 in gastric cancer and adjacent normal gastric tissues. The protein expression levels of NUAK2 were detected by western blot analysis. The effects of NUAK2 expression on the proliferation of gastric cancer cells was detected using an MTT and BrdU incorporation assay. Furthermore, the effects of NUAK2 on proliferation and cancer stem cell markers, both protein and microRNA (miRNA), were investigated by western blot analysis and miRNA microarrays, respectively. The results demonstrated that NUAK2 was able to significantly promote the proliferation of SGC-7901 gastric cancer cells. In addition, NUAK2 overexpression decreased the percentage of cells in the G1 phase and increased the percentage of cells in the S phase. Western blot analysis and miRNA microarrays revealed that overexpression of NUAK2 resulted in increased expression levels of proliferation markers, including c-myc, proliferating cell nuclear antigen, cyclin-dependent kinase 2, miRNA 21, and gastric cancer stem cell markers, including aldehyde dehydrogenase 1, CD44 and CD133. In conclusion, NUAK2 expression differed between the tumor and normal gastric tissues. NUAK2 was able to promote the proliferation of gastric cancer cells and regulate their cell cycle. Proliferation and cancer stem cell markers were upregulated by NUAK2 expression. Therefore, the results from the present study suggest that NUAK2 may be a promising target for gastric cancer therapy in the future. PMID:28352350

  19. Significance of microRNA 21 in gastric cancer.

    PubMed

    Sekar, Durairaj; Krishnan, Ramalingam; Thirugnanasambantham, Krishnaraj; Rajasekaran, Baskaran; Islam, Villianur Ibrahim Hairul; Sekar, Punitha

    2016-11-01

    Despite promising developments of treatment, the mortality due to gastric cancer remains high and the mechanisms of gastric cancer initiation and the development also remains elusive. It has been reported that patients with positive serologic tests for H. pylori have a higher risk of the development of gastric cancer. microRNAs (miRNAs) are short non-coding RNA molecules consisting of 21-25 nucleotides (nt) in length. The miRNAs silence their cognate target genes by inhibiting mRNA translation or degrading the mRNA molecules by binding to their 3'-untranslated (UTR) regions and plays a very important role in cancer biology. Recent evidences indicate that miR-21 is overexpressed in tumour tissue, including gastric cancer and plays a vital role in tumour cell proliferation, apoptosis, invasion and angiogenesis. Elevated levels of miR-21 is associated with downregulation of tumour suppressor genes, such as programmed cell death 4 (PDCD4), tissue inhibitor of metalloproteinase 3, phosphatase and tensin homolog (PTEN), tropomyosin 1, ras homolog gene family member B, and maspin. Silencing of miR-21 through the use of a miR-21 inhibitor affected cancer cell viability, induced cell cycle arrest and increased chemosensitivity to anticancer agents indicating that miR-21 functions as an oncogene. Although an increased expression level of miR-21 has been observed in gastric cancer, studies related to the role of miR-21 in gastric cancer progression is very limited. The main thrust of this mini review is to explain the potency of miR-21 as a prognostic and/or diagnostic biomarker and as a new target for clinical therapeutic for interventions of gastric cancer progression.

  20. Report on the National Survey of Photodynamic Therapy (PDT) for Gastric Cancer in Japan (a secondary publication)

    PubMed Central

    Oinuma, Takeshi; Nishiwaki, Yoshiro

    2016-01-01

    Background and Aims: A national survey of photodynamic therapy (PDT) was carried out in order to understand the present situation in Japan and the efficacy of PDT for gastric cancer. Materials and Methods: A questionnaire concerning with PDT was sent to all hospitals performing or previously performed PDT. The answers were collected and analyzed. An additional investigation about efficacy of PDT for gastric cancer was conducted for the main 3 hospitals. Results: In 18 of 19 responded hospitals, PDT was performed for 386 cases of superficial early gastric cancer and for 27 cases of advanced gastric cancer. In the 3 main hospitals, a complete response was achieved in 42 of 57 patients (73.7%) of superficial early gastric cancer not indicated for surgery or other endoscopic treatments such as endoscopic submucosal dissection. No serious complication occurred. Conclusions: PDT has been shown to be a safe and effective treatment for early gastric cancer, not only for the intramucosal type, but also for the submucosal invasion. PDT will be one of the important endoscopic treatments for gastric cancer especially in a super ageing society like Japan. PMID:27721560

  1. Screening for and surveillance of gastric cancer.

    PubMed

    Compare, Debora; Rocco, Alba; Nardone, Gerardo

    2014-10-14

    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.

  2. Changing Trends in Gastric Cancer Surgery

    PubMed Central

    Özer, İlter; Bostancı, Erdal Birol; Ulaş, Murat; Özoğul, Yusuf; Akoğlu, Musa

    2017-01-01

    Gastric cancer is one of the most common causes of cancer-related death. It requires multimodal treatment and surgery is the most effective treatment modality. Radical surgery includes total or subtotal gastrectomy with lymph node dissection. The extent of lymphadenectomy still remains controversial. Eastern surgeons have performed D2 or more extended lymphadenectomy while their Western colleagues have performed more limited lymph node dissection. However, the trend has been changing in favour of D2 lymph node dissection in both hemispheres. Currently, D2 is the recommended type of lymphadenectomy in experienced centres in the west. In Japan, D2 lymph node dissection is the standard surgical approach. More extensive lymphadenectomy than D2 has not been found to be associated with improved survival and generally is not performed. Bursectomy and splenectomy are additional controversial issues in surgical performance, and trends regarding them will be discussed. The performance of bursectomy is controversial and there is no clear evidence of its clinical benefit. However, a trend toward better survival in patients with serosal invasion has been reported. Routine splenectomy as a part of lymph node dissection has largely been abandoned, although splenectomy is recommended in selected cases. Minimally invasive surgery has gained wide popularity and indications for minimally invasive procedures have been expanding due to increasing experience and improving technology. Neoadjuvant therapy has been shown to have beneficial effects and seems necessary to provide a survival benefit. Diagnostic laparoscopy should be kept in mind prior to treatment. PMID:28251018

  3. Comprehensive characterization of the genomic alterations in human gastric cancer

    PubMed Central

    Cui, Juan; Yin, Yanbin; Ma, Qin; Wang, Guoqing; Olman, Victor; Zhang, Yu; Chou, Wen-Chi; Hong, Celine S.; Zhang, Chi; Cao, Sha; Mao, Xizeng; Li, Ying; Qin, Steve; Zhao, Shaying; Jiang, Jing; Hastings, Phil; Li, Fan; Xu, Ying

    2016-01-01

    Gastric cancer is one of the most prevalent and aggressive cancers worldwide, and its molecular mechanism remains largely elusive. Here we report the genomic landscape in primary gastric adenocarcinoma of human, based on the complete genome sequences of five pairs of cancer and matching normal samples. In total, 103,464 somatic point mutations, including 407 nonsynonymous ones, were identified and the most recurrent mutations were harbored by Mucins (MUC3A and MUC12) and transcription factors (ZNF717, ZNF595 and TP53). 679 genomic rearrangements were detected, which affect 355 protein-coding genes; and 76 genes show copy number changes. Through mapping the boundaries of the rearranged regions to the folded three-dimensional structure of human chromosomes, we determined that 79.6% of the chromosomal rearrangements happen among DNA fragments in close spatial proximity, especially when two endpoints stay in a similar replication phase. We demonstrated evidences that microhomology-mediated break-induced replication was utilized as a mechanism in inducing ~40.9% of the identified genomic changes in gastric tumor. Our data analyses revealed potential integrations of Helicobacter pylori DNA into the gastric cancer genomes. Overall a large set of novel genomic variations were detected in these gastric cancer genomes, which may be essential to the study of the genetic basis and molecular mechanism of the gastric tumorigenesis. PMID:25422082

  4. Local resection of the stomach for gastric cancer.

    PubMed

    Kinami, Shinichi; Funaki, Hiroshi; Fujita, Hideto; Nakano, Yasuharu; Ueda, Nobuhiko; Kosaka, Takeo

    2016-06-24

    The local resection of the stomach is an ideal method for preventing postoperative symptoms. There are various procedures for performing local resection, such as the laparoscopic lesion lifting method, non-touch lesion lifting method, endoscopic full-thickness resection, and laparoscopic endoscopic cooperative surgery. After the invention and widespread use of endoscopic submucosal dissection, local resection has become outdated as a curative surgical technique for gastric cancer. Nevertheless, local resection of the stomach in the treatment of gastric cancer in now expected to make a comeback with the clinical use of sentinel node navigation surgery. However, there are many issues associated with local resection for gastric cancer, other than the normal indications. These include gastric deformation, functional impairment, ensuring a safe surgical margin, the possibility of inducing peritoneal dissemination, and the associated increase in the risk of metachronous gastric cancer. In view of these issues, there is a tendency to regard local resection as an investigative treatment, to be applied only in carefully selected cases. The ideal model for local resection of the stomach for gastric cancer would be a combination of endoscopic full-thickness resection of the stomach using an ESD device and hand sutured closure using a laparoscope or a surgical robot, for achieving both oncological safety and preserved functions.

  5. Prognostic effects of 25-hydroxyvitamin D levels in gastric cancer

    PubMed Central

    2012-01-01

    Background Results from large epidemiologic studies on the association between vitamin D and gastric cancer are controversial. Vitamin D significantly promotes apoptosis in the undifferentiated gastric cancer cell, but the prognostic effects of its levels are unknown. Methods 197 gastric carcinoma patients who received treatment in the cancer centre of Sun Yat-sen University from January 2002 to January 2006 were involved in the study. The stored blood drawn before any treatment was assayed for 25-hydroxyvitamin D levels. The clinicopathologic data were collected to examine the prognostic effects of vitamin D. Results The mean vitamin D levels of the 197 gastric patients was 49.85 ± 23.68 nmol/L, among whom 114(57.9%) were deficient in Vitamin D(< 50 nmol/L), 67(34%) were insufficient (50-75 nmol/L) and 16(8.1%) were sufficient (> 75 nmol/L). Clinical stage (P = 0.004) and lymph node metastasis classification (P = 0.009) were inversely associated with vitamin D levels. The patients with high vitamin D levels group (≥ 50 nmol/L) had a higher overall survival compared with the low vitamin D levels group (< 50 nmol/L)(P = 0.018). Multivariate analysis indicated that vitamin D levels were an independent prognostic factor of gastric cancer (P = 0.019). Conclusions Vitamin D deficiency may be associated with poor prognosis in gastric cancer. PMID:22284859

  6. A case-control study of gastric cancer in Venezuela.

    PubMed

    Muñoz, N; Plummer, M; Vivas, J; Moreno, V; De Sanjosé, S; Lopez, G; Oliver, W

    2001-08-01

    A case-control study to evaluate risk factors for gastric cancer was carried out among 292 cases of gastric cancer and 485 controls in a high-risk area of Venezuela. Subjects were interviewed using a structured questionnaire, which elicited information on residential history, socio-economic status, family history of gastric diseases, smoking, drinking and dietary habits. Habitual diet was estimated from a meal-structured food frequency questionnaire on 75 food items. There was a strong inverse association with social class, as measured by education and by indicators of poverty. The results of the dietary analysis suggest that a diet high in starch and low in meat, fish and fresh vegetables increases risk of gastric cancer. A protective effect was observed for frequent consumption of allium vegetables. Inverse associations were found with height, which may reflect nutritional status in childhood, and with refrigerator use in the first two decades of life. Alcohol and tobacco consumption was investigated among males only, since the prevalence of alcohol and tobacco use was very low in females. Alcohol drinkers were at higher risk than non-drinkers and there was a small excess risk for current smokers compared with never smokers. There was some evidence of familial aggregation of gastric cancer. These findings will have important implications in planning preventive strategies for gastric cancer in Venezuela.

  7. Differential MicroRNA Expression Between Gastric Cancer Tissue and Non-cancerous Gastric Mucosa According to Helicobacter pylori Status

    PubMed Central

    Lee, Jung Won; Kim, Nayoung; Park, Ji Hyun; Kim, Hee Jin; Chang, Hyun; Kim, Jung Min; Kim, Jin-Wook; Lee, Dong Ho

    2017-01-01

    Background MicroRNAs (miRNAs) are key post-translational mechanisms which can regulate gene expression in gastric carcinogenesis. To identify miRNAs responsible for gastric carcinogenesis, we compared expression levels of miRNAs between gastric cancer tissue and non-cancerous gastric mucosa according to Helicobacter pylori status. Methods Total RNA was extracted from the cancerous regions of formalin-fixed, paraffin-embedded tissues of H. pylori-positive (n = 8) or H. pylori-negative (n = 8) patients with an intestinal type of gastric cancer. RNA expression was analyzed using a 3,523 miRNA profiling microarray based on the Sanger miRBase. Validation analysis was performed using TaqMan miRNA assays for biopsy samples from 107 patients consisted of control and gastric cancer with or without H. pylori. And then, expression levels of miRNAs were compared according to subgroups. Results A total of 156 miRNAs in the aberrant miRNA profiles across the miRNA microarray showed differential expression (at least a 2-fold change, P < 0.05) in cancer tissue, compared to noncancerous mucosa in both of H. pylori-negative and -positive samples. After 10 promising miRNAs were selected, validations by TaqMan miRNA assays confirmed that two miRNAs (hsa-miR-135b-5p and hsa-miR-196a-5p) were significantly increased and one miRNA (hsa-miR-145-5p) decreased in cancer tissue compared to non-cancerous gastric mucosa at H. pylori-negative group. For H. pylori-positive group, three miRNAs (hsa-miR-18a-5p, hsa-miR-135b-5p, and hsa-miR-196a-5p) were increased in cancer tissue. hsa-miR-135b-5p and hsa-miR-196a-5p were increased in gastric cancer in both of H. pylori-negative and -positive. Conclusions miRNA expression of the gastric cancer implies that different but partially common gastric cancer carcinogenic mechanisms might exist according to H. pylori status. PMID:28382284

  8. Relationship between Social Network and Stage of Adoption of Gastric Cancer Screening among the Korean Population.

    PubMed

    Lee, Myung Ha; Choi, Kui Son; Lee, Yoon Young; Suh, Mina; Jun, Jae Kwan

    2013-01-01

    Few studies have examined the relationship between social support and stages of adoption of cancer screening. Here we investigated associations between both structural and functional aspects of social support and stages of adoption of gastric cancer screening in the general population of Korea. The study population was derived from the 2011 Korean National Cancer Screening Survey (KNCSS), an annual cross-sectional survey that uses nationally representative random sampling to investigate cancer screening rates. Data were analyzed from 3,477 randomly selected respondents aged 40-74 years. Respondents were classified according to their stage of adoption of gastric cancer screening: precontemplation (13.2%), contemplation (18.0%), action/maintenance (56.1%), relapse risk (8.5%), and relapse stage (4.1%). Respondents with larger social networks were more likely to be in the contemplation/action/maintenance, or the relapse risk/relapse stages versus the precontemplation stage (OR=1.91, 95%CI: 1.52-2.91; p for tend=0.025). Emotional and instrumental supports were not associated with any stage of adoption of gastric cancer screening. However, respondents who reported receiving sufficient informational support were more likely to be in the relapse risk/relapse stages versus the precontemplation, or the contemplation/action/maintenance stage (p for trend=0.016). Interventions involving interactions between social network members could play an important role in increasing participation in gastric cancer screening.

  9. 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.

  10. Towards personalized perioperative treatment for advanced gastric cancer

    PubMed Central

    Miao, Ru-Lin; Wu, Ai-Wen

    2014-01-01

    Gastric cancer is one of the most frequently diagnosed cancers worldwide. Although the rate of gastric cancer has declined dramatically over the past decades in most developed Western countries, it has not declined in East Asia. Currently, a radical gastrectomy is still the only curative treatment for gastric cancer. Over the last twenty years, however, surgery alone has been replaced by a multimodal perioperative approach. To achieve the maximum benefit from the perioperative treatment, a thorough evaluation of the tumor must first be performed. A complete assessment of gastric cancer is divided into two parts: staging and histology. According to the stage and histology of the cancer, perioperative chemotherapy or radiochemotherapy can be implemented, and perioperative targeted therapies such as trastuzumab may also play a role in this field. However, perioperative treatment approaches have not been widely accepted until a series of clinical trials were performed to evaluate the value of perioperative treatment. Although multimodal perioperative treatment has been widely applied in clinical practice, personalization of perioperative treatment represents the next stage in the treatment of gastric cancer. Genomic-guided treatment and efficacy prediction using molecular biomarkers in perioperative treatment are of great importance in the evolution of treatment and may become an ideal treatment method. PMID:25206266

  11. [Epigenetics in the pathogenesis and early detection of gastric cancer].

    PubMed

    Corvalán R, Alejandro

    2013-12-01

    Gastric cancer is the first cause of death for cancer in Chile. The recently identified genetic alterations in these tumors have not yielded new biomarkers for the disease. Epigenetics or the study of reversible genomic changes that do not affect protein codifying DNA sequences but cause phenotypic disturbances, is identifying new cancer biomarkers. Specifically, the loss of expression caused by the covalent link of a methyl group to carbon 5 of cytosine (DNA hypermethylation) is extensively evaluated. Performing an epigenetic evaluation of 24 genes, we have identified eight genes associated to the aggressive signet ring cell type gastric cancer, the association between APC hypermethylation and worse prognosis and BRCA1 hypermethylation association with early onset of gastric cancer. The most interesting findings are the hypermethylation of Reprimo gene in plasma as a population biomarker and the tissue over expression of p73 gene (as a consequence of hypomethylation) as a high risk indicator of progression to gastric cancer. All these findings are indicating an important role of epigenetics in the pathogenesis and early detection of gastric cancer.

  12. Targeting HER 2 and angiogenesis in gastric cancer.

    PubMed

    Jomrich, G; Schoppmann, S F

    2016-01-01

    Gastric cancer is one of the most commonly diagnosed and the second leading cause of cancer death worldwide. Surgery combined with multimodal therapy remains the only curative therapy. However, local relapse or distant metastases occur in more than 50% of radically resected patients. Due to molecular therapies, targeting HER2 and angiogenesis, major advances in the treatment of gastric cancer could be achieved. Nevertheless, development of resistance to monoclonal antibodies, such as trastuzumab, is arising. Currently a number of promising new therapeutic are under investigation, combining chemotherapy with newly developed agents to overcome cancer resistance. In this review we report current clinical applications of targeted therapies and overview ongoing trials, investigating the use of monoclonal antibodies in (HER2 positive) gastric cancer.

  13. Lymph node dissection for gastric cancer: a critical review

    PubMed Central

    Batista, Thales Paulo; Martins, Mário Rino

    2012-01-01

    Gastric cancer is one of the most common neoplasms and an important cause of cancer-related death worldwide. Efforts to reduce its high mortality rates are currently focused on multidisciplinary management. However, surgery remains a cornerstone in the management of patients with resectable disease. There is still some controversy as to the extent of lymph node dissection for potentially curable stomach cancer. Surgeons in eastern countries favor more extensive lymph node dissection, whereas those in the West favor less extensive dissection. Thus, extent of lymph node dissection remains one of the most hotly discussed aspects of gastric surgery, particularly because most stomach cancers are now often comprehensively treated by adding some perioperative chemotherapy or chemo-radiation. We provide a critical review of lymph nodes dissection for gastric cancer with a particular focus on its benefits in a multimodal approach. PMID:25992202

  14. Relevant prognostic factors in gastric cancer: ten-year results of the German Gastric Cancer Study.

    PubMed Central

    Siewert, J R; Böttcher, K; Stein, H J; Roder, J D

    1998-01-01

    OBJECTIVE: In 1986 a prospective multicenter observation trial in patients with resected gastric cancer was initiated in Germany. An analysis of prognostic factors based on the 10-year survival data is now presented. PATIENTS AND METHODS: A total of 1654 patients treated for gastric cancer between 1986 and 1989 at 19 centers in Germany and Austria were included. The resected specimen were evaluated histopathologically according to a standardized protocol. The extent of lymphadenectomy was classified after surgery based on the number of removed lymph nodes on histopathologic assessment (25 or fewer removed nodes, D1 or standard lymphadenectomy; >25 removed nodes, D2 or extended lymphadenectomy). Endpoint of the study was death. Follow-up is complete for 97% of the included patients (median follow-up of the surviving patients is 8.4 years). Prognostic factors were assessed by multivariate analysis. RESULTS: A complete macroscopic and microscopic tumor resection (R0 resection according to the UICC 1997) could be achieved in 1182 of the 1654 patients (71.5%). The calculated 10-year survival rate in the entire patient population was 26.3% +/- 4.7%; it was 36.1% +/- 1.6% after an R0 resection. In the total patient population there was an independent prognostic effect of the ratio between invaded and removed lymph nodes, the residual tumor (R) category, the pT category, the presence of postsurgical complications, and the presence of distant metastases. Multivariate analysis in the subgroup of patients who had a UICC R0 resection confirmed the nodal status, the pT category, and the presence of postsurgical complications as the major independent prognostic factors. The extent of lymph node dissection had a significant and independent effect on the 10-year survival rate in patients with stage II tumors. This effect was present in the subgroups with (pT2N1) and without (pT3N0) lymph node metastases on standard histopathologic assessment. The beneficial effect of extended

  15. Airborne exposures and risk of gastric cancer: a prospective cohort study.

    PubMed

    Sjödahl, Krister; Jansson, Catarina; Bergdahl, Ingvar A; Adami, Johanna; Boffetta, Paolo; Lagergren, Jesper

    2007-05-01

    There is an unexplained male predominance among patients with gastric cancer, and many carcinogens are found in male-dominated dusty occupations. However, the relation between occupational exposures and risk of gastric cancer remains unclear. To investigate whether airborne occupational exposures might influence the risk of noncardia gastric cancer, we used a large, prospective cohort study of male Swedish construction workers. These workers were, during the period 1971-1993, regularly invited to health examinations by a nationwide occupational health service organization. Data on job titles and other variables were collected through self-administered questionnaires and forms completed by the health organization's staff. Industrial hygienists assessed 12 specific airborne occupational exposures for 200 job titles. Gastric cancer, death or emigration occurring during follow-up in 1971-2002 were identified by linkage to the Swedish registers of Cancer, Causes of Death and Total Population, respectively. Incidence rate ratios (IRR) and 95% confidence intervals (CI), adjusted for attained age, tobacco smoking, calendar period and body mass, were derived from Cox regression. Among 256,357 cohort members, contributing 5,378,012 person-years at risk, 948 noncardia gastric cancers were identified. Increased risk of this tumor was found among workers exposed to cement dust (IRR 1.5 [95% CI 1.1-2.1]), quartz dust (IRR 1.3 [95% CI 1.0-1.7]) and diesel exhaust (IRR 1.4 [95% CI 1.1-1.9]). Dose-response relations were observed for these exposures. No consistent positive associations were found regarding exposure to asbestos, asphalt fumes, concrete dust, epoxy resins, isocyanates, metal fumes, mineral fibers, organic solvents or wood dust. In conclusion, this study provides some support to the hypothesis that specific airborne exposures increase the risk of noncardia gastric cancer.

  16. Clinical implications of proliferation activity in T1 or T2 male gastric cancer patients.

    PubMed

    Kim, Young-Woo; Eom, Bang Wool; Kook, Myeong-Cherl; Kim, Han-Seong; Kim, Mi-Kyung; Hwang, Hai-Li; Chandra, Vishal; Poojan, Shiv; Song, Yura; Koh, Jae-Soo; Bae, Chang-Dae; Ro, Jungsil; Hong, Kyeong-Man

    2015-11-06

    Proliferation activity has already been established as a prognostic marker or as a marker for anticancer drug sensitivity. In gastric cancer, however, the prognostic significance of proliferation activity is still being debated. Several studies evaluating proliferation activity using Ki-67 have shown controversial results in terms of the relationship between proliferation activity and overall survival (OS) or drug sensitivity in gastric cancer patients. Because cytoskeleton-associated protein 2 (CKAP2) staining has recently been introduced as a marker of proliferation activity, we analyzed 437 gastric cancer tissues through CKAP2 immunohistochemistry, and we evaluated the chromatin CKAP2-positive cell count (CPCC) for proliferation activity. Although the CPCC did not show any significant correlation with OS in the male, female or total number of cases, it did show a significant correlation in the T1 or T2 male patient subgroup, according to log-rank tests (P=0.001) and univariate analysis (P=0.045). Additionally, multivariate analysis with the Cox proportional hazard regression model showed a significant correlation between the CPCC and OS (P=0.039) for the co-variables of age, gender, T stage, N stage, histology, tumor location, tumor size and adjuvant chemotherapy. In male gastric cancer cell lines, faster-growing cancer cells showed higher sensitivity to cisplatin than slow-growing cells. Thus our study indicates that CPCC-measured proliferation activity demonstrates a significantly worse prognosis in T1 or T2 male gastric cancer patients. The CPCC will help to more precisely classify gastric cancer patients and to select excellent candidates for adjuvant chemotherapy, which in turn will facilitate further clinical chemotherapeutic trials.

  17. Association of common variants on chromosome 8q24 with gastric cancer in Venezuelan patients.

    PubMed

    Labrador, Luis; Torres, Keila; Camargo, Maria; Santiago, Laskhmi; Valderrama, Elvis; Chiurillo, Miguel Angel

    2015-07-15

    Gastric cancer remains one of the leading causes of death in the world, being Central and South America among the regions showing the highest incidence and mortality rates worldwide. Although several single nucleotide polymorphisms (SNPs) identified in the chromosomal region 8q24 by genome-wide association studies have been related with the risk of different kinds of cancers, their role in the susceptibility of gastric cancer in Latin American populations has not been evaluated yet. Hereby, we performed a case-control study to explore the associations between three SNPs at 8q24 and gastric cancer risk in Venezuelan patients. We analyzed rs1447295, rs4733616 and rs6983267 SNPs in 122 paraffin-embedded tumor samples from archival bank and 129 samples with chronic gastritis (obtained by upper endoscopy during the study) from the Central Hospital of Barquisimeto (Lara, Venezuela). Genotypes were determined by PCR-RFLP reactions designed in this study for efficient genotyping of formalin-fixed/paraffin-embedded tissues. No significant differences in genotype frequencies between case and control groups were found. However, carriers of the homozygous TT genotype of SNP rs4733616 had an increased risk of developing poorly differentiated gastric cancer according to the codominant (OR=3.59, P=0.035) and the recessive models (OR=4.32, P=0.014, best-fitting model of inheritance), adjusted by age and gender. Our study suggests that the SNP rs4733616 is associated with susceptibility to poorly differentiated gastric cancer in Venezuelans. Additional studies are needed to further interrogate the prognostic value of the rs4733616 marker in this high-risk population for gastric cancer.

  18. Systemic and mucosal humoral responses to Helicobacter pylori in gastric cancer.

    PubMed Central

    Crabtree, J E; Wyatt, J I; Sobala, G M; Miller, G; Tompkins, D S; Primrose, J N; Morgan, A G

    1993-01-01

    The systemic IgG response to Helicobacter pylori was examined in 70 patients with gastric cancer. H pylori IgG antibodies were assayed by enzyme linked immunosorbent assay (ELISA), and serological recognition of H pylori antigens was characterised by western blotting. A percentage of 78.5 were seropositive by ELISA. Two of five patients under age 50 were seronegative. Positivity was unrelated to age, sex, tumour type, or site. Ninety one per cent of ELISA positive cancer patients recognised the H pylori cytotoxin associated 120 kilodalton (kD) protein, significantly more than a control group of 47 ELISA positive patients with non-ulcer dyspepsia (72%). Four of 15 ELISA negative cancer patients also showed recognition of this protein in western blots. Mucosal IgA responses to H pylori were examined by immunoblotting supernatants of in vitro cultured resected antral mucosa in an overlapping group of 19 gastric cancer patients. Eighteen had a positive response, including 10 of 11 negative for H pylori by biopsy urease testing. The systemic and local immunoblotting results show that the high seroprevalence of H pylori antibodies detected by ELISA is nevertheless an underestimate of past infection. Dyspepsia screening policies based solely on H pylori ELISA would miss some young patients with gastric cancer. Further study of the relation of the H pylori cytotoxin to gastric precancerous lesions is warranted. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:8244098

  19. 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

  20. Gastric cancer risk factors in subjects with family history.

    PubMed

    Muñoz, S E; Ferraroni, M; La Vecchia, C; Decarli, A

    1997-02-01

    Until now, it has been unclear whether there are differences in various risk factor profiles for familial gastric cancer, i.e., gastric cancer among subjects with a family history of the disease. A total of 722 gastric cancer patients and 2024 controls were admitted between 1985 and 1992 to a network of hospitals in the Greater Milan area. Of these, 88 cases and 103 controls who reported a family history of gastric cancer in first degree relatives were considered in the present analysis. There was no relationship between gastric cancer risk and tobacco smoking or alcohol drinking. Shorter duration of electrical refrigerator use was related to a nonsignificant increased risk and a high daily meal frequency was associated with an increased gastric cancer risk. Significant direct trends of risk were observed for pasta (odds ratio, OR = 4.20 for the highest versus the lowest tertile), bread (OR, 2.86), red meat (OR, 3.38), and preserved meat (OR, 1.90). Inverse associations were observed for increasing consumption of selected vegetables and fruits, chiefly peppers (OR = 0.31), total fruits (OR, 0.47), and citrus fruits (OR, 0.38). With reference to selected micronutrients, a significant inverse trend in risk with increasing consumption for beta-carotene (OR, 0.27) and ascorbic acid (OR, 0.20) was observed. These results suggest that dietary risk factors for subjects with a family history of gastric cancer in first-degree relatives are not appreciably different from well-established risk factors of the disease in the general population.

  1. 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

  2. Time trend analysis of gastric cancer incidence in Japan by histological types, 1975-1989

    PubMed Central

    Kaneko, S; Yoshimura, T

    2001-01-01

    Since different histological types (HT) of gastric cancer (GC) may differ in their aetiology, time trend analysis by HT may afford an insight into aetiology. From the Gastric Cancer Registry of Japan, 161 067 cases diagnosed were retrieved between 1975 and 1989 to calculate the annual relative frequencies, stratified by age group and sex, of HT according to the Lauren and the Japanese Research Society for Gastric Cancer (JRSGC) classifications. Age- and sex-specific incidence rates by HT were estimated by multiplying the corresponding national cancer incidence rates of GC by the relative frequencies. Logistic regression models stratified by sex and age group were fitted to determine the time trends of HT. Using the Lauren classification, a decreasing trend of the intestinal type and a stable trend of the diffuse type were found. By the JRSGC classification, significant decreasing trends for most age groups were found for papillary and mucinous adenocarcinomas. Tubular adenocarcinomas (well differentiated type) showed a decreasing trend only in younger age groups. Tubular (moderately differentiated type), poorly differentiated adenocarcinomas, and signet ring cell carcinoma were statistically stable during the period. Considering changes in lifestyles of the Japanese, the result suggests that there are three aetiological types of GC. © 2001 Cancer Research Campaign http://www.bjcancer.com PMID:11161407

  3. Localization of thymidine phosphorylase in advanced gastric and colorectal cancer.

    PubMed

    Kobayashi, Michiya; Okamoto, Ken; Akimori, Toyokazu; Tochika, Naoshige; Yoshimoto, Tadashi; Okabayashi, Takehiro; Sugimoto, Takeki; Araki, Keijiro

    2004-01-01

    Thymidine phosphorylase (TP) is known to be more concentrated in human cancer tissues than in adjacent normal tissue based on findings using enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry. However, the ultrastructural localization of TP in cancer tissues has not previously been demonstrated. We investigated the localization of TP in gastric cancer and colorectal cancer tissue by ELISA, immunohistochemistry, and immunoelectron microscopy. Between April 1997 and May 2000, we obtained surgically resected specimens from 42, 46, and 36 cases of advanced gastric, colon, and rectal cancer, respectively. ELISA demonstrated that the TP level was higher in cancer tissues than in adjacent normal tissue. Immunohistochemically, cancer cells were positive for the enzyme in some cases. However, in a number of cases immunopositive inflammatory cells were also present in cancerous tissues. At the electron microscope level, TP was diffusely distributed in the cytoplasm of cancer cells and in the mitochondria of the neutrophil in gastric cancer tissue. In rectal cancer tissues, cytoplasmic granules in macrophages in cancer tissues were immunoreactive for the TP. These findings suggest that TP is produced by macrophages and exists in neutrophils and cancer cells.

  4. 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

  5. Perioperative chemotherapy for resectable gastric cancer - what is the evidence?

    PubMed

    Bringeland, Erling A; Wasmuth, Hans H; Grønbech, Jon E

    2017-02-28

    The UK MAGIC trial published in 2006 was the first RCT to identify improved long-term survival rates using preoperative chemotherapy for resectable gastric or gastroesophageal cancer. Overnight, the treatment regimen impacted European guidelines. However, the majority of patients underwent limited lymph node dissection, and analyses of the rates of curative resection, downsizing and downstaging were not by intention to treat, rightfully raising concerns about their validity. For the subset of true gastric cancers, meta-analyses may even question the claims of improved long-term survival rates by present-day regimens. A rhetorical question can be posed as to whether downstaging and improved survival rates by preoperative (radio)-chemotherapy for cancers of the distal esophagus or gastric cardia, has confounded our conclusions on the (lack of) effect of present-day regimens of perioperative chemotherapy for true gastric cancers, let alone in a situation with proper lymph node dissection. At present, a plea can be made to move one step back and revert to an RCT with a surgery alone arm. Inclusion criteria and analyses of future RCTs must stratify on tumor location and the Lauren type and embrace the newly developed scheme of sub-classification of gastric cancers based on extensive molecular profiling as reported in the seminal Cancer Genome Atlas Study.

  6. 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

  7. 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

  8. Ischemic Gastropathic Ulcer Mimics Gastric Cancer.

    PubMed

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

    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.

  9. Clinical significance of NOTCH1 intracellular cytoplasmic domain translocation into the nucleus in gastric cancer

    PubMed Central

    Saito, Shinichiro; Ishiguro, Hideyuki; Kimura, Masahiro; Ogawa, Ryo; Miyai, Hirotaka; Tanaka, Tatsuya; Mizoguchi, Koji; Takeyama, Hiromitsu

    2016-01-01

    Recent studies have shown constitutive activation of the Notch signaling pathway in various types of malignancies. However, it remains unclear whether this signaling pathway is activated in gastric cancer. In the present study, the aim was to investigate the role of Notch signaling in gastric cancer by investigating the subcellular localization of Notch-associated proteins in tissue samples from gastric cancer patients. Samples were obtained from 115 gastric cancer patients who had undergone surgery at the Department of Gastroenterological Surgery, Nagoya City University Graduate School of Medical Science without pre-operative chemotherapy or radiation. Subsequently the correlation between translocation of NOTCH1 intracellular cytoplasmic domain (NICD) into the nucleus (as measured by immunostaining) and survival in gastric cancer patients after surgery was investigated. The results were analyzed in reference to the patients' clinicopathological characteristics and the effects of these results on patient prognosis were determined. Significant correlations were observed between NICD nuclear localization and clinicopathological characteristics, such as tumor status (T factor), lymph node status (N factor), pathological stage and differentiation status. No significant correlations were observed between NICD nuclear localization and age, gender, tumor location, vein invasion or lymphatic invasion. Patients with >30% of cancer cell nuclei positively stained for NICD (as revealed by immunostaining) were associated with a significantly shorter survival following surgery than patients with <30% NICD-positive cancer cell nuclei (log-rank test, P=0.0194). Univariate analysis revealed that among the clinicopathological factors examined, T factor [risk rate (RR)=10.870; P=0.0016], N factor (RR=41.667; P=0.0003), lymphatic invasion (RR=13.158; P=0.0125), vein invasion (RR=25.000; P= 0.0019) and translocation of NICD to the nucleus (RR=3.937; P=0.0312) were all identified to be

  10. 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

  11. Approach to the surgical management of resectable gastric cancer.

    PubMed

    Quadri, Humair S; Hong, Young K; Al-Refaie, Waddah B

    2016-04-01

    The rates of gastric cancer, which is the third leading cause of cancer-related deaths worldwide, vary depending on geographic location. Margin-negative gastrectomy and adequate lymphadenectomy (removal of ≥15 lymph nodes) are the cornerstones of multimodal treatment for operable gastric cancer. Diagnostic laparoscopy should be included in the armamentarium for newly diagnosed gastric cancer in order to overcome the limitations of cross-sectional imaging in identifying sub-radiographic hepatic or peritoneal metastases. The benefit of surgical therapy is enhanced by at least 13% when it is integrated with multimodal therapy: either surgery followed by adjuvant chemoradiotherapy or surgery with perioperative systemic therapy. This multidisciplinary approach to treatment will continue to be an evolving paradigm, especially with the emergence of systemic and targeted therapies.

  12. Approach to the surgical management of resectable gastric cancer.

    PubMed

    Quadri, Humair S; Hong, Young K; Al-Refaie, Waddah B

    2016-03-01

    The rates of gastric cancer, which is the third leading cause of cancer-related deaths worldwide, vary depending on geographic location. Margin-negative gastrectomy and adequate lymphadenectomy (removal of ≥15 lymph nodes) are the cornerstones of multimodal treatment for operable gastric cancer. Diagnostic laparoscopy should be included in the armamentarium for newly diagnosed gastric cancer in order to overcome the limitations of cross-sectional imaging in identifying sub-radiographic hepatic or peritoneal metastases. The benefit of surgical therapy is enhanced by at least 13% when it is integrated with multimodal therapy: either surgery followed by adjuvant chemoradiotherapy or surgery with perioperative systemic therapy. This multidisciplinary approach to treatment will continue to be an evolving paradigm, especially with the emergence of systemic and targeted therapies.

  13. Expression of ornithine decarboxylase in precancerous and cancerous gastric lesions

    PubMed Central

    Miao, Xin-Pu; Li, Jian-Sheng; Li, Hui-Yan; Zeng, Shi-Ping; Zhao, Ye; Zeng, Jiang-Zheng

    2007-01-01

    AIM: To investigate the expression of ornithine decarboxylase (ODC) in precancerous and cancerous gastric lesions. METHODS: We studied the expression of ODC in gastric mucosa from patients with chronic superficial gastritis (CSG, n = 32), chronic atrophic gastritis [CAG, n = 43; 15 with and 28 without intestinal metaplasia (IM)], gastric dysplasia (DYS, n = 11) and gastric cancer (GC, n = 48) tissues using immunohistochemical staining. All 134 biopsy specimens of gastric mucosa were collected by gastroscopy. METHODS: The positive rate of ODC expression was 34.4%, 42.9%, 73.3%, 81.8% and 91.7% in cases with CSG, CAG without IM, CAG with IM, DYS and GC, respectively (P < 0.01), The positive rate of ODC expression increased in the order of CSG < CAG (without IM) < CAG (with IM) < DYS and finally, GC. In addition, ODC positive immunostaining rate was lower in well-differentiated GC than in poorly-differentiated GC (P < 0.05). CONCLUSION: The expression of ODC is positively correlated with the degree of malignity of gastric mucosa and development of gastric lesions. This finding indicates that ODC may be used as a good biomarker in the screening and diagnosis of precancerous lesions. PMID:17569126

  14. 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

  15. Interaction of sonic hedgehog (SHH) pathway with cancer stem cell genes in gastric cancer.

    PubMed

    Samadani, Ali Akbar; Akhavan-Niaki, Haleh

    2015-03-01

    Gastric cancer may appear by frequent genetic or epigenetic changes in oncogenes, tumor suppressor or DNA mismatch repair genes. Molecular studies show the possibility of involvement of certain cancer pathways in gastric cancer. In this respect, DNA methylation is one of the most important epigenetic alterations in gastric cancer and identifying the signaling mechanism and also methylation of some genes that are involved in gastric cancer can help to improve treatment strategies. Relatively, there are many reported methylation alteration of genes in stem cells in all kinds of tumors with some of these genes having a key role in tumor development. Correspondingly, KLF5, CDX1/2, WNT1 and FEM1A are considerable genes in gastric cancer, although many researches and studies have illustrated that sonic hedgehog and expression of its signaling cascade proteins are related in gastric cancer. Relatively, modification in these genes causes many eclectic cancers such as rhabdomyosarcoma and diverse kinds of digestive system tumor development. Conspicuously, these master genes have a noticeable role in stem cell's growth regulation as well as other kinds of cancer such as breast cancer and leukemia. Hence, we concluded that research and studies on methylation and expression of these genes and also the investigation of molecular signaling in gastric cancer can acquire impressive conclusions in order to control and treat this common place and serious problem.

  16. An integrated transcriptomic and computational analysis for biomarker identification in gastric cancer

    PubMed Central

    Cui, Juan; Chen, Yunbo; Chou, Wen-Chi; Sun, Liankun; Chen, Li; Suo, Jian; Ni, Zhaohui; Zhang, Ming; Kong, Xiaoxia; Hoffman, Lisabeth L.; Kang, Jinsong; Su, Yingying; Olman, Victor; Johnson, Darryl; Tench, Daniel W.; Amster, I. Jonathan; Orlando, Ron; Puett, David; Li, Fan; Xu, Ying

    2011-01-01

    This report describes an integrated study on identification of potential markers for gastric cancer in patients’ cancer tissues and sera based on: (i) genome-scale transcriptomic analyses of 80 paired gastric cancer/reference tissues and (ii) computational prediction of blood-secretory proteins supported by experimental validation. Our findings show that: (i) 715 and 150 genes exhibit significantly differential expressions in all cancers and early-stage cancers versus reference tissues, respectively; and a substantial percentage of the alteration is found to be influenced by age and/or by gender; (ii) 21 co-expressed gene clusters have been identified, some of which are specific to certain subtypes or stages of the cancer; (iii) the top-ranked gene signatures give better than 94% classification accuracy between cancer and the reference tissues, some of which are gender-specific; and (iv) 136 of the differentially expressed genes were predicted to have their proteins secreted into blood, 81 of which were detected experimentally in the sera of 13 validation samples and 29 found to have differential abundances in the sera of cancer patients versus controls. Overall, the novel information obtained in this study has led to identification of promising diagnostic markers for gastric cancer and can benefit further analyses of the key (early) abnormalities during its development. PMID:20965966

  17. Identification of IL11RA and MELK amplification in gastric cancer by comprehensive genomic profiling of gastric cancer cell lines

    PubMed Central

    Calcagno, Danielle Queiroz; Takeno, Sylvia Santomi; Gigek, Carolina Oliveira; Leal, Mariana Ferreira; Wisnieski, Fernanda; Chen, Elizabeth Suchi; Araújo, Taíssa Maíra Thomaz; Lima, Eleonidas Moura; Melaragno, Maria Isabel; Demachki, Samia; Assumpção, Paulo Pimentel; Burbano, Rommel Rodriguez; Smith, Marília Cardoso

    2016-01-01

    AIM To identify common copy number alterations on gastric cancer cell lines. METHODS Four gastric cancer cell lines (ACP02, ACP03, AGP01 and PG100) underwent chromosomal comparative genome hybridization and array comparative genome hybridization. We also confirmed the results by fluorescence in situ hybridization analysis using the bacterial artificial chromosome clone and quantitative real time PCR analysis. RESULTS The amplification of 9p13.3 was detected in all cell lines by both methodologies. An increase in the copy number of 9p13.3 was also confirmed by fluorescence in situ hybridization analysis. Moreover, the interleukin 11 receptor alpha (IL11RA) and maternal embryonic leucine zipper kinase (MELK) genes, which are present in the 9p13.3 amplicon, revealed gains of the MELK gene in all the cell lines studied. Additionally, a gain in the copy number of IL11RA and MELK was observed in 19.1% (13/68) and 55.9% (38/68) of primary gastric adenocarcinoma samples, respectively. CONCLUSION The characterization of a small gain region at 9p13.3 in gastric cancer cell lines and primary gastric adenocarcinoma samples has revealed MELK as a candidate target gene that is possibly related to the development of gastric cancer. PMID:27920471

  18. 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

  19. Diet and gastric cancer: a casecontrol study in Fujian Province, China.

    PubMed

    Ye, Wei-Min; Yi, Ying-Nan; Luo, Ren-Xia; Zhou, Tian-Shu; Lin, Ru-Tao; Chen, Gui-Dong

    1998-12-01

    AIM:To explore the relationship between consumption of fish sauce, other dietary factors, living habits and the rish kf gastric cancer.METHODS:From May 1994 to July 1995, a population-based 1 2 case-control study was in Carried out inhigh-risk areas of gastric cancer, Changle and Fuqing cities, Fujian Province. Totally 272 cases and 544 age, gender-matched controls were included. Risk state analyses were made by ASRS package.RESULTS:Risk state single-factor analysis indicated that gastric cancer risk rose with high intake of fish sauce(OR =2.57), salted vegetables (OR =1.41), salted/fried fish and small shrimps (OR =1.57), low consumption of fresh vegetables (OR =1.95), fresh citrus fruits (OR =1.41), other fresh fruits (OR =1.31), green tea (OR =1.72), exposure to moldy foods (OR =2.32), irregular dinners (OR =5.47) and familial history of malignancy (OR =3.27).No significant relationship was observed between smoking, drinking, salt intake, use of refrigerator and gastric cancer rish. The results of rish state conditional Logistic regression showed that fish sauce, salted/dried fish and small shrimps, irregular dinners, familial history of malignancy were included in the best rish set. The summary ARS for the four factors was 75.49%.CONCLUSION:High intake of fish sauce, salted foods, moldy foods, irregular dinners and familial history of malignancy were possible risk factors for gastric cancer, whereas fresh vegetables and fruits.and green tea might have protective effects for gastric cancer.

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

    PubMed

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

    2016-02-10

    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.

  1. Concurrent apatinib and local radiation therapy for advanced gastric cancer

    PubMed Central

    Zhang, Ming; Deng, Weiye; Cao, Xiaoci; Shi, Xiaoming; Zhao, Huanfen; Duan, Zheping; Lv, Bonan; Liu, Bin

    2017-01-01

    Abstract Rationale: Apatinib is a novel anti-angiogenic agent targeting vascular endothelial growth factor receptor-2, which is effective in patients with chemotherapy-refractory gastric cancer. There are no reports of concurrent apatinib with local radiation therapy in elderly patients with advanced gastric cancer. Patient concerns and Diagnoses: we present the first published report of a 70-year-old male patient with advanced gastric cancer who received concurrent apatinib and local radiation therapy after failure of oxaliplatin and S-1 chemotherapy. Interventions and Outcomes: The patient received concurrent apatinib and local radiation therapy and was followed up 7 months after therapy without disease progress, 14 months later indicated extensive metastasis and this patient died of pulmonary infection. Lessons: Elderly patients with advanced gastric cancer may benefit from concurrent apatinib with local radiation therapy when chemotherapy is not tolerated or successful. Further studies are needed to investigate the clinical outcomes and toxicities associated with concurrent apatinib and radiation therapy in gastric cancer. PMID:28248891

  2. Potential capacity of endoscopic screening for gastric cancer in Japan.

    PubMed

    Hamashima, Chisato; Goto, Rei

    2017-01-01

    In 2016, the Japanese government decided to introduce endoscopic screening for gastric cancer as a national program. To provide endoscopic screening nationwide, we estimated the proportion of increase in the number of endoscopic examinations with the introduction of endoscopic screening, based on a national survey. The total number of endoscopic examinations has increased, particularly in clinics. Based on the national survey, the total number of participants in gastric cancer screening was 3 784 967. If 30% of the participants are switched from radiographic screening to endoscopic screening, approximately 1 million additional endoscopic examinations are needed. In Japan, the participation rates in gastric cancer screening and the number of hospitals and clinics offering upper gastrointestinal endoscopy vary among the 47 prefectures. If the participation rates are high and the numbers of hospitals and clinics are small, the proportion of increase becomes larger. Based on the same assumption, 50% of big cities can provide endoscopic screening with a 5% increase in the total number of endoscopic examinations. However, 16.7% of the medical districts are available for endoscopic screening within a 5% increase in the total number of endoscopic examinations. Despite the Japanese government's decision to introduce endoscopic screening for gastric cancer nationwide, its immediate introduction remains difficult because of insufficient medical resources in rural areas. This implies that endoscopic screening will be initially introduced to big cities. To promote endoscopic screening for gastric cancer nationwide, the disparity of medical resources must first be resolved.

  3. 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.

  4. Different gastric microbiota compositions in two human populations with high and low gastric cancer risk in Colombia

    PubMed Central

    Yang, Ines; Woltemate, Sabrina; Piazuelo, M. Blanca; Bravo, Luis E.; Yepez, Maria Clara; Romero-Gallo, Judith; Delgado, Alberto G.; Wilson, Keith T.; Peek, Richard M.; Correa, Pelayo; Josenhans, Christine; Fox, James G.; Suerbaum, Sebastian

    2016-01-01

    Inhabitants of Túquerres in the Colombian Andes have a 25-fold higher risk of gastric cancer than inhabitants of the coastal town Tumaco, despite similar H. pylori prevalences. The gastric microbiota was recently shown in animal models to accelerate the development of H. pylori-induced precancerous lesions. 20 individuals from each town, matched for age and sex, were selected, and gastric microbiota analyses were performed by deep sequencing of amplified 16S rDNA. In parallel, analyses of H. pylori status, carriage of the cag pathogenicity island and assignment of H. pylori to phylogeographic groups were performed to test for correlations between H. pylori strain properties and microbiota composition. The gastric microbiota composition was highly variable between individuals, but showed a significant correlation with the town of origin. Multiple OTUs were detected exclusively in either Tumaco or Túquerres. Two operational taxonomic units (OTUs), Leptotrichia wadei and a Veillonella sp., were significantly more abundant in Túquerres, and 16 OTUs, including a Staphylococcus sp. were significantly more abundant in Tumaco. There was no significant correlation of H. pylori phylogeographic population or carriage of the cagPAI with microbiota composition. From these data, testable hypotheses can be generated and examined in suitable animal models and prospective clinical trials. PMID:26729566

  5. Different gastric microbiota compositions in two human populations with high and low gastric cancer risk in Colombia.

    PubMed

    Yang, Ines; Woltemate, Sabrina; Piazuelo, M Blanca; Bravo, Luis E; Yepez, Maria Clara; Romero-Gallo, Judith; Delgado, Alberto G; Wilson, Keith T; Peek, Richard M; Correa, Pelayo; Josenhans, Christine; Fox, James G; Suerbaum, Sebastian

    2016-01-05

    Inhabitants of Túquerres in the Colombian Andes have a 25-fold higher risk of gastric cancer than inhabitants of the coastal town Tumaco, despite similar H. pylori prevalences. The gastric microbiota was recently shown in animal models to accelerate the development of H. pylori-induced precancerous lesions. 20 individuals from each town, matched for age and sex, were selected, and gastric microbiota analyses were performed by deep sequencing of amplified 16S rDNA. In parallel, analyses of H. pylori status, carriage of the cag pathogenicity island and assignment of H. pylori to phylogeographic groups were performed to test for correlations between H. pylori strain properties and microbiota composition. The gastric microbiota composition was highly variable between individuals, but showed a significant correlation with the town of origin. Multiple OTUs were detected exclusively in either Tumaco or Túquerres. Two operational taxonomic units (OTUs), Leptotrichia wadei and a Veillonella sp., were significantly more abundant in Túquerres, and 16 OTUs, including a Staphylococcus sp. were significantly more abundant in Tumaco. There was no significant correlation of H. pylori phylogeographic population or carriage of the cagPAI with microbiota composition. From these data, testable hypotheses can be generated and examined in suitable animal models and prospective clinical trials.

  6. Effect of pravastatin on the survival of patients with advanced gastric cancer

    PubMed Central

    Bujanda, Luis; Rodríguez-González, Araceli; Sarasqueta, Cristina; Eizaguirre, Emma; Hijona, Elizabeth; Marín, José J.G.; Perugorria, María J.; Banales, Jesús M.; Cosme, Angel

    2016-01-01

    Objectives A fluoropyrimidine plus cisplatin combined with surgery is standard first-line treatment for advanced gastric cancer. We evaluated the effect of pravastatin on overall survival in patients with advanced gastric cancer in a prospective cohort study. Methods At the time of surgery, we assigned 60 patients with advanced gastric cancer (stage III or IV) to receive standard first-line treatment (control group) or standard first-line treatment plus pravastatin at a dose of 40 mg once daily (pravastatin group). The minimum follow-up period was 4 years and the maximum of 6 years. Results The mean of age was 66 years and the TNM stage was III and IV in 65% and 35% of patients, respectively. There was no significant difference between the two groups (control vs pravastatin) in median overall survival (15 vs 14 months; P = 0.8). Predictors of survival were the stage (hazard ratio of death stage IV (III stage as reference): 4.4; 95% CI: 2–9.7; p < 0.05) and older age (hazard ratio of death ≥ 65 years (< 65 years as reference): 2.8; 95% CI: 1.3–6; p < 0.05). Conclusions Pravastatin did not improve outcome in patients with advanced gastric cancer. PMID:26735890

  7. Sensitivity of endoscopic screening for gastric cancer by the incidence method.

    PubMed

    Hamashima, Chisato; Okamoto, Mikizo; Shabana, Michiko; Osaki, Yoneatsu; Kishimoto, Takuji

    2013-08-01

    Although radiographic screening for gastric cancer has been conducted in Japan, it is anticipated that endoscopy will become a new screening method because of its high detection rate. The sensitivities of endoscopic and radiographic screening were calculated by the detection method and the incidence method based on the results of community-based screening in Japan. There were 56,676 screenings for gastric cancer using endoscopy and radiography from April 2002 to March 2007 in Yonago, Japan. The target age group was from 40 to 79 years. Screen-detected and interval cancers were investigated based on a screening database linked to the Tottori Cancer Registry. All gastric cancers diagnosed within 1 year after a negative screen were considered interval cancers. Based on the screening history, these were divided into prevalence screening and incidence screening. Prevalence screenings included 7,388 for endoscopic screening and 5,410 for radiographic screening, whereas incidence screenings included 18,021 for endoscopic screening and 11,417 for radiographic screening. The sensitivity of prevalence screening calculated by the incidence method was 0.886 (95% confidence interval [CI] = 0.698-0.976) for endoscopic screening and 0.831 (95% CI = 0.586-0.964) for radiographic screening; however, the difference was not significant (p = 0.626). The sensitivity of incidence screening calculated by the incidence method was 0.954 (95% CI = 0.842-0.994) for endoscopic screening and 0.855 (95% CI = 0.637-0.970) for radiographic screening (p = 0.177). Endoscopic screening for gastric cancer had a higher sensitivity than radiographic screening by the incidence method in both screening rounds. However, further study is needed to evaluate mortality reduction and to estimate overdiagnosis with endoscopic screening for gastric cancer.

  8. Occupational asbestos exposure and risk of esophageal, gastric and colorectal cancer in the prospective Netherlands Cohort Study.

    PubMed

    Offermans, Nadine S M; Vermeulen, Roel; Burdorf, Alex; Goldbohm, R Alexandra; Keszei, András P; Peters, Susan; Kauppinen, Timo; Kromhout, Hans; van den Brandt, Piet A

    2014-10-15

    The evidence for an association between occupational asbestos exposure and esophageal, gastric and colorectal cancer is limited. We studied this association specifically addressing risk differences between relatively low and high exposure, risk associated with cancer subtypes, the influence of potential confounders and the interaction between asbestos and smoking in relation to cancer risk. Using the Netherlands Cohort Study (n = 58,279 men, aged 55-69 years at baseline), asbestos exposure was estimated by linkage to a job-exposure matrix. After 17.3 years of follow-up, 187 esophageal, 486 gastric and 1,724 colorectal cancer cases were available for analysis. The models adjusted for age and family history of cancer showed that mainly (prolonged) exposure to high levels of asbestos was statistically significantly associated with risk of esophageal adenocarcinoma (EAC), total and distal colon cancer and rectal cancer. For overall gastric cancer and gastric non-cardia adenocarcinoma (GNCA), also exposure to lower levels of asbestos was associated. Additional adjustment for lifestyle confounders, especially smoking status, yielded non-significant associations with overall gastric cancer and GNCA in the multivariable-adjusted model, except for the prolonged highly exposed subjects (tertile 3 vs. never: HR 2.67, 95% CI: 1.11-6.44 and HR 3.35, 95% CI: 1.33-8.44, respectively). No statistically significant additive or multiplicative interaction between asbestos and smoking was observed for any of the studied cancers. This prospective population-based study showed that (prolonged) high asbestos exposure was associated with overall gastric cancer, EAC, GNCA, total and distal colon cancer and rectal cancer.

  9. Chestnut extract induces apoptosis in AGS human gastric cancer cells.

    PubMed

    Lee, Hyun Sook; Kim, Eun Ji; Kim, Sun Hyo

    2011-06-01

    In Korea, chestnut production is increasing each year, but consumption is far below production. We investigated the effect of chestnut extracts on antioxidant activity and anticancer effects. Ethanol extracts of raw chestnut (RCE) or chestnut powder (CPE) had dose-dependent superoxide scavenging activity. Viable numbers of MDA-MD-231 human breast cancer cells, DU145 human prostate cancer cells, and AGS human gastric cancer cells decreased by 18, 31, and 69%, respectively, following treatment with 200 µg/mL CPE for 24 hr. CPE at various concentrations (0-200 µg/mL) markedly decreased AGS cell viability and increased apoptotic cell death dose and time dependently. CPE increased the levels of cleaved caspase-8, -7, -3, and poly (ADP-ribose) polymerase in a dose-dependent manner but not cleaved caspase-9. CPE exerted no effects on Bcl-2 and Bax levels. The level of X-linked inhibitor of apoptosis protein decreased within a narrow range following CPE treatment. The levels of Trail, DR4, and Fas-L increased dose-dependently in CPE-treated AGS cells. These results show that CPE decreases growth and induces apoptosis in AGS gastric cancer cells and that activation of the death receptor pathway contributes to CPE-induced apoptosis in AGS cells. In conclusion, CPE had more of an effect on gastric cancer cells than breast or prostate cancer cells, suggesting that chestnuts would have a positive effect against gastric cancer.

  10. Beyond precision surgery: Molecularly motivated precision care for gastric cancer.

    PubMed

    Choi, Y Y; Cheong, J-H

    2017-03-01

    Gastric cancer is one of the leading causes of cancer-related deaths worldwide. Despite the high disease prevalence, gastric cancer research has not gained much attention. Recently, genome-scale technology has made it possible to explore the characteristics of gastric cancer at the molecular level. Accordingly, gastric cancer can be classified into molecular subtypes that convey more detailed information of tumor than histopathological characteristics, and these subtypes are associated with clinical outcomes. Furthermore, this molecular knowledge helps to identify new actionable targets and develop novel therapeutic strategies. To advance the concept of precision patient care in the clinic, patient-derived xenograft (PDX) models have recently been developed. PDX models not only represent histology and genomic features, but also predict responsiveness to investigational drugs in patient tumors. Molecularly curated PDX cohorts will be instrumental in hypothesis generation, biomarker discovery, and drug screening and testing in proof-of-concept preclinical trials for precision therapy. In the era of precision medicine, molecularly tailored therapeutic strategies should be individualized for cancer patients. To improve the overall clinical outcome, a multimodal approach is indispensable for advanced cancer patients. Careful, oncological principle-based surgery, combined with a molecularly guided multidisciplinary approach, will open new horizons in surgical oncology.

  11. Gastric cancer screening uptake trends in Korea: results for the National Cancer Screening Program from 2002 to 2011: a prospective cross-sectional study.

    PubMed

    Lee, Sangeun; Jun, Jae Kwan; Suh, Mina; Park, Boyoung; Noh, Dai Keun; Jung, Kyu-Won; Choi, Kui Son

    2015-02-01

    Although the effectiveness of mass screening for gastric cancer remains controversial, several countries with a high prevalence of gastric cancer have implemented nationwide gastric cancer screening programs. This study was conducted to assess trends in the use of either upper gastrointestinal series (UGIS) or endoscopy to screen for gastric cancer, as well as to assess factors strongly associated with changes therein, over a 10-year period. Data were obtained from the National Cancer Screening Program (NCSP) database from 2002 to 2011 in Korea. The NCSP provides biennial gastric cancer screening with either UGIS or endoscopy for men and women aged ≥40 years. Using the NCSP database, overall screening rates for gastric cancer and percentages of endoscopy use among participants were analyzed from 2002 to 2011. To estimate changes in participation rates and endoscopy use over time, we assessed the average annual percentage change (APC) by comparing the rates from 2002 and 2011 as relative rates. Participation rates for gastric cancer screening increased 4.33% annually from 2002 to 2011. In terms of screening method, a substantial increase in endoscopy use was noted among the gastric cancer screening participants over the 10-year period. The percentage of participants who had undergone endoscopy test increased from 31.15% in 2002 to 72.55% in 2011, whereas the percentage of participants who underwent UGIS decreased tremendously. Increased endoscopy test use was greatest among participants aged 40 to 49 (APC = 4.83%) and Medical Aid Program recipients (APC = 5.73%). Overall, men, participants of ages 40 to 49 years, and National Health Insurance beneficiaries of higher socioeconomic status were more likely to undergo screening via endoscopy. This study of nationwide empirical data from 2002 to 2011 showed that endoscopy is increasingly being used for gastric cancer screening in Korea, compared with UGIS. Nevertheless, further study of the impact of endoscopy

  12. Methylation subtypes and large-scale epigenetic alterations in gastric cancer.

    PubMed

    Zouridis, Hermioni; Deng, Niantao; Ivanova, Tatiana; Zhu, Yansong; Wong, Bernice; Huang, Dan; Wu, Yong Hui; Wu, Yingting; Tan, Iain Beehuat; Liem, Natalia; Gopalakrishnan, Veena; Luo, Qin; Wu, Jeanie; Lee, Minghui; Yong, Wei Peng; Goh, Liang Kee; Teh, Bin Tean; Rozen, Steve; Tan, Patrick

    2012-10-17

    Epigenetic alterations are fundamental hallmarks of cancer genomes. We surveyed the landscape of DNA methylation alterations in gastric cancer by analyzing genome-wide CG dinucleotide (CpG) methylation profiles of 240 gastric cancers (203 tumors and 37 cell lines) and 94 matched normal gastric tissues. Cancer-specific epigenetic alterations were observed in 44% of CpGs, comprising both tumor hyper- and hypomethylation. Twenty-five percent of the methylation alterations were significantly associated with changes in tumor gene expression. Whereas most methylation-expression correlations were negative, several positively correlated methylation-expression interactions were also observed, associated with CpG sites exhibiting atypical transcription start site distances and gene body localization. Methylation clustering of the tumors revealed a CpG island methylator phenotype (CIMP) subgroup associated with widespread hypermethylation, young patient age, and adverse patient outcome in a disease stage-independent manner. CIMP cell lines displayed sensitivity to 5-aza-2'-deoxycytidine, a clinically approved demethylating drug. We also identified long-range regions of epigenetic silencing (LRESs) in CIMP tumors. Combined analysis of the methylation, gene expression, and drug treatment data suggests that certain LRESs may silence specific genes within the region, rather than all genes. Finally, we discovered regions of long-range tumor hypomethylation, associated with increased chromosomal instability. Our results provide insights into the epigenetic impact of environmental and biological agents on gastric epithelial cells, which may contribute to cancer.

  13. Trends in gastric cancer mortality and in the prevalence of Helicobacter pylori infection in Portugal.

    PubMed

    Morais, Samantha; Ferro, Ana; Bastos, Ana; Castro, Clara; Lunet, Nuno; Peleteiro, Bárbara

    2016-07-01

    Portugal has the highest gastric cancer mortality rates in Western Europe, along with high prevalences of Helicobacter pylori infection. Monitoring their trends is essential to predict the burden of this cancer. We aimed to quantify time trends in gastric cancer mortality in Portugal and in each administrative region, and to compute short-term predictions, as well as to describe the prevalence of H. pylori infection, through a systematic review. Joinpoint analyses were used to identify significant changes in sex-specific trends in gastric cancer age-standardized mortality rates (ASMR) and to estimate annual percent changes (APC). The most recent trends were considered to compute estimates up to 2020 by adjusting Poisson regression models. We searched PubMed and IndexRMP to identify studies carried out in Portugal reporting the prevalence of H. pylori. Gastric cancer mortality has been decreasing in Portugal since 1971 in men (from ASMR=55.3/100 000; APC=-2.4, 95% confidence interval: -2.5 to -2.3) and since 1970 in women (from ASMR=28.0/100 000; APC=-2.8, 95% confidence interval: -2.9 to -2.7), although large regional differences were observed. Predicted ASMR for 2015 and 2020 were 18.8/100 000 and 16.7/100 000 for men and 8.5/100 000 and 7.4/100 000 for women, respectively. The prevalence of H. pylori varied from almost 5% at 0.5-2 years to just over 90% at 70 years or more. No consistent variation was observed since the 1990s. The downward trends in mortality rates are expected to remain in the next decades. The high prevalence of H. pylori infection across age groups and studies from different periods shows a large potential for decrease in the burden of gastric cancer in Portugal.

  14. 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

  15. 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.

  16. Prognostic significance of KLF4 expression in gastric cancer

    PubMed Central

    Hashimoto, Isaya; Nagata, Takuya; Sekine, Shinichi; Moriyama, Makoto; Shibuya, Kazuto; Hojo, Shozo; Matsui, Koshi; Yoshioka, Isaku; Okumura, Tomoyuki; Hori, Takashi; Shimada, Yutaka; Tsukada, Kazuhiro

    2017-01-01

    To understand the roles of pluripotent stem cell-inducing genes in gastric cancer, the expression of Krüppel-like factor 4 (KLF4), Nanog, octamer-binding transcription factor 4 (Oct4), avian myelocytomatosis viral oncogene homolog (c-Myc) and sex-determining region Y-box 2 (SOX2) was examined using the newly developed gastric carcinoma tissue microarray. The associations between the immunohistochemical expression levels of the pluripotency-inducing factors and the clinicopathological data of 108 patients with gastric cancer were analyzed. No associations were identified between the expression levels of the five pluripotency-inducing factors and the tumor-node-metastasis (TNM) classification or clinicopathological characteristics of the patients. In addition, multivariate analysis revealed no association of Nanog, Oct4, SOX2 or c-Myc with the prognosis of the gastric cancer patients; however, low expression of KLF4 was determined to be an independent negative prognostic factor (P=0.0331), particularly in patients who underwent R0 resection (TNM stages 2 and 3; P=0.0048). In summary, low KLF4 expression was found to be negatively associated with overall survival, and may therefore be a useful prognostic marker in gastric cancer patients. PMID:28356964

  17. Role of peptidylarginine deiminase type 4 in gastric cancer

    PubMed Central

    Xin, Jiang; Song, Xiuqi

    2016-01-01

    Peptidylarginine deiminase type 4 (PADI4) post-translationally converts peptidylarginine to citrulline, appearing to be overexpressed in numerous carcinomas. The current study aimed to investigate the expression of PADI4 in gastric cancer tissues and its effect on the biological activities of SGC-7901 and AGS tumor cell lines. The expression of PADI4 was determined in gastric cancer and normal gastric mucosa tissues using western blot analysis and reverse transcription-quantitative polymerase chain reaction. Gastric cancer cell lines were divided into the following groups: Mock group (subjected to transfection reagent); negative group [subjected to small interfering RNA (siRNA) transfection]; PADI4 siRNA group (subjected to PADI4 siRNA transfection); 5-fluorouracil (5-Fu) group (subjected to 5-Fu); and 5-Fu + siRNA transfection group (subjected to 5-Fu and PADI4 siRNA transfection). The effects of silencing PADI4 with the above measures on the proliferation and invasion of SGC-7901 and AGS cells were determined by MTT and Transwell chamber assays. In addition, propidium iodide staining was performed to detect the effects of PADI4 on the cell cycle. A significant increase in the expression of PADI4 mRNA in gastric cancer tissue compared with normal mucosa tissue was identified (P<0.05). The proliferation and invasion of SGC-7901 and AGS cells were significantly decreased in the PADI4 siRNA group. Furthermore, flow cytometry DNA analysis revealed that silencing PADI4 resulted in significant S phase arrest and marked decrease of cells in the G2/M phase. PADI4 siRNA coupled with 5-Fu significantly enhanced its inhibitory effect on the proliferation of gastric cancer cells. In conclusion, PADI4 demonstrated high expression in gastric cancer and served an important role in the biological activities of gastric cancer cells involving cell proliferation, invasion and cell cycle. As a result, PADI4 may be a valid cancer susceptibility gene and potential target for cancer

  18. Expression of claudin-11, -23 in different gastric tissues and its relationship with the risk and prognosis of gastric cancer

    PubMed Central

    Sun, Liping; Gong, Yuehua; Chen, Moye; Wang, Zeyang; Yuan, Yuan

    2017-01-01

    Claudins play an important role in regulating the permeability of epithelial and endothelial cells and in the maintenance of cell polarity. We aimed to investigate expression of claudin-11, -23 in different gastric tissues and its relationship with clinicopathologic parameters and prognosis of gastric cancer. We compared their expression levels in the paired cancerous tissues versus those in the adjacent noncancerous tissues by real-time PCR, western blotting and immunohistochemistry. The results showed that the expression of claudin-11, -23 was greatly increased in paracancerous gastric tissue compared with cancerous tissue. We also compared their expression levels of tissues from gastric cancer, superficial gastritis, and atrophic gastritis by immunohistochemistry. The results indicated that the expression of claudin-11 and 23 was significantly higher in superficial gastritis than that in atrophic gastritis and gastric cancer. The expression of claudin-23 was significantly lower in atrophic gastritis than that in gastric cancer, but no obviously difference was observed for claudin-11. As for analysis of clinicopathologic parameters of gastric cancer, logistic multiple regression indicated that claudin-11 was significantly associated with sex, smoking, alcohol, H. pylori infection and Borrmann classification while claudin-23 was significantly associated with vessel cancer embolus. Cox multivariate survival analysis indicated that gastric cancer patients with negative claudin-23 expression had significantly longer overall survival. In conclusion, the expression of claudin-11, -23 was remarkably downregulated in gastric cancer. Abnormal expression of these proteins was significantly correlated with some clinicopathologic parameters. In particular, claudin-23 positive expression was associated with poor prognostic outcomes of gastric cancer patients and may therefore serve as an independent prognosticator of patient survival. PMID:28350854

  19. Screening of gastric cancer: who, when, and how.

    PubMed

    Lin, Jaw-Town

    2014-01-01

    Gastric cancer (GC) remains the leading cause of cancer mortality worldwide. Conceivably, early diagnosis may be achievable through screening of the high-risk population. Therefore, it is important to identify individuals harboring premalignant lesions that include atrophic gastritis, intestinal metaplasia, and mucosal dysplasia. The age threshold for GC screening depends on the regional incidence and the individual risk. In high-incidence countries such as Japan and Korea, the age to screen GC may be as early as 40 years. The mass screening by endoscopy in these countries would be able to detect a substantial portion of patients with early GCs as well as precancerous lesions. For the purpose of eliminating GC, however, these screening programs should be conducted in conjunction with Helicobacter pylori eradication. In low-incidence countries, it seems feasible to adopt a stepwise approach to identify high-risk individuals at first. The initial screening should focus on epidemiologic factors, genetic or hereditary risks, and the status of H pylori infection. Measurement of serum pepsinogen I and II and gastrin may detect atrophic gastritis in a noninvasive manner. Patients with these premalignant lesions should then receive endoscopic examination and enter surveillance. To date, there is no cost-effective strategy for an average-risk individual from a population with low incidence of GC, and therefore screening is unwarranted and cannot be recommended for them.

  20. Aging, immunity, and cancer.

    PubMed

    Fulop, Tamas; Larbi, Anis; Kotb, Rami; de Angelis, Flavia; Pawelec, Graham

    2011-06-01

    Age is the most important risk factor for tumorigenesis. More than 60% of new cancers and more than 70% of cancer deaths occur in elderly subjects >65 years. The immune system plays an important role in the battle of the host against cancer development. Deleterious alterations occur to the immune response with aging, termed immunosenescence. It is tempting to speculate that this waning immune response contributes to the higher incidence of cancer, but robust data on this important topic are few and far between. This review is devoted to discussing state of the art knowledge on the relationship between immunosenescence and cancer. Emerging understanding of the aging process at the molecular level is viewed from the perspective of this increased tumorigenesis. We also consider some of the most recent means to intervene in the modulation of immunosenescence to increase the ability of the immune system to fight against tumors. Future research will unravel new aspects of the immune response against tumors which will be modulable to decrease the burden of cancer in elderly individuals.

  1. Dynamic Changes in Helicobacter pylori Status Following Gastric Cancer Surgery

    PubMed Central

    Yoon, Kichul; Kim, Nayoung; Kim, Jaeyeon; Lee, Jung Won; Lee, Hye Seung; Lee, Jong-Chan; Yoon, Hyuk; Shin, Cheol Min; Park, Young Soo; Ahn, Sang-Hoon; Park, Do Joong; Kim, Hyung Ho; Lee, Yoon Jin; Lee, Kyoung-Ho; Kim, Young-Hoon; Lee, Dong Ho

    2017-01-01

    Background/Aims Helicobacter pylori eradication is recommended in patients with early gastric cancer. However, the possibility of spontaneous regression raises a question for clinicians about the need for “retesting” postoperative H. pylori status. Methods Patients who underwent curative gastrectomy at Seoul National University Bundang Hospital and had a positive H. pylori status without eradication therapy at the time of gastric cancer diagnosis were prospectively enrolled in this study. H. pylori status and atrophic gastritis (AG) and intestinal metaplasia (IM) histologic status were assessed pre- and postoperatively. Results One hundred forty patients (mean age, 59.0 years; 60.7% male) underwent subtotal gastrectomy with B-I (65.0%), B-II (27.1%), Roux-en-Y (4.3%), jejunal interposition (0.7%), or proximal gastrectomy (4.3%). Preoperative presence of AG (62.9%) and IM (72.9%) was confirmed. The mean period between surgery and the last endoscopic follow-up was 38.0±25.6 months. Of the 140 patients, 80 (57.1%) were found to be persistently positive for H. pylori, and 60 (42.9%) showed spontaneous negative conversion at least once during follow-up. Of these 60 patients, eight (13.3%) showed more complex postoperative dynamic changes between negative and positive results. The spontaneous negative conversion group showed a trend of having more postoperative IM compared to the persistent H. pylori group. Conclusions A high percentage of spontaneous regression and complex dynamic changes in H. pylori status were observed after partial gastrectomy, especially in individuals with postoperative histological IM. It is better to consider postoperative eradication therapy after retesting for H. pylori. PMID:27840366

  2. Prognostic value of preoperative serum tumor markers in gastric cancer

    PubMed Central

    Huang, Ze-Bo; Zhou, Xin; Xu, Jun; Du, Yi-Ping; Zhu, Wei; Wang, Jian; Shu, Yong-Qian; Liu, Ping

    2014-01-01

    AIM: To evaluate the prognostic value of preoperative carcinoembryonic antigen (CEA), carbohydrate antigen (CA)19-9, and CA50 in patients undergoing D2 resection. METHODS: We evaluated 363 patients with gastric cancer who underwent gastrectomy at our hospital from January 2006 to December 2009. Blood samples were obtained from each patient within 1 wk before surgery. The cut-off values for serum CEA, CA19-9, and CA50 were 5 ng/mL, 37 U/mL, and 20 U/mL, respectively. The correlation between preoperative tumor marker levels and prognosis was studied by means of univariate and multivariate analyses. RESULTS: The preoperative serum positive rates of CEA, CA19-9 and CA50 were 24.0%, 18.9% and 24.5%, respectively. The positivity rate of serum CEA was significantly correlated with age (P < 0.001), sex (P = 0.022), tumor size (P = 0.007) and depth of invasion (P = 0.018); CA19-9 with tumor size (P = 0.042) and lymph node metastasis (P < 0.001); and CA50 only with lymph node metastasis (P = 0.001). In multivariate analysis, tumor size, T category, N category, vascular or neural invasion, and adjuvant chemotherapy were independent prognostic factors for overall survival. CA19-9 had an independent prognostic significance in patients without adjuvant chemotherapy (P = 0.027). CONCLUSION: Preoperative serum CEA, CA19-9 and CA50 are prognostic in patients with gastric cancer. Only CA19-9 is an independent prognostic factor after surgery without adjuvant chemotherapy. PMID:24829865

  3. Molecular classifiers for gastric cancer and nonmalignant diseases of the gastric mucosa.

    PubMed

    Meireles, Sibele I; Cristo, Elier B; Carvalho, Alex F; Hirata, Roberto; Pelosof, Adriane; Gomes, Luciana I; Martins, Waleska K; Begnami, Maria D; Zitron, Cláudia; Montagnini, André L; Soares, Fernando A; Neves, E Jordão; Reis, Luiz F L

    2004-02-15

    High incidence of gastric cancer-related death is mainly due to diagnosis at an advanced stage in addition to the lack of adequate neoadjuvant therapy. Hence, new tools aimed at early diagnosis would have a positive impact in the outcome of the disease. Using cDNA arrays having 376 genes either identified previously as altered in gastric tumors or known to be altered in human cancer, we determined expression signature of 99 tissue fragments representing normal gastric mucosa, gastritis, intestinal metaplasia, and adenocarcinomas. We first validated the array by identifying molecular markers that are associated with intestinal metaplasia, considered as a transition stage of gastric adenocarcinomas of the intestinal type as well as markers that are associated with diffuse type of gastric adenocarcinomas. Next, we applied Fisher's linear discriminant analysis in an exhaustive search of trios of genes that could be used to build classifiers for class distinction. Many classifiers could distinguish between normal and tumor samples, whereas, for the distinction of gastritis from tumor and for metaplasia from tumor, fewer classifiers were identified. Statistical validations showed that trios that discriminate between normal and tumor samples are powerful classifiers to distinguish between tumor and nontumor samples. More relevant, it was possible to identify samples of intestinal metaplasia that have expression signature resembling that of an adenocarcinoma and can now be used for follow-up of patients to determine their potential as a prognostic test for malignant transformation.

  4. Altered expression of PTCH and HHIP in gastric cancer through their gene promoter methylation: novel targets for gastric cancer.

    PubMed

    Song, Yu; Tian, Ye; Zuo, Yun; Tu, Jian-Cheng; Feng, Yu-Fang; Qu, Chen-Jiang

    2013-04-01

    Human hedgehog-interacting protein (HHIP) and protein patched homolog (PTCH) are two negative regulators of the hedgehog signal, however, the mechanism of action in gastric cancer is unknown. Methylation of TSG promoters has been considered as a causative mechanism of tumorigenesis. In the present study, we first determined the expression of PTCH and HHIP mRNA and protein in gastric cancer tissues and adjacent normal tissues, and then detected methylation of the two genes to associate their expression and gene promoter methylation in gastric cancer. Expression in gastric cancer tissues and the cancer cells (AGS) were evaluated by reverse transcription-PCR (RT-PCR), qRT-PCR and IHC, while the methylation expression was valued by methylation-specific PCR (MSP) and bisulfite sequencing PCR (BSP). Cell viability and apoptosis were analyzed by MTT assay and flow cytometry following treatment with 5-aza-dc. Results showed that PTCH and HHIP expression was reduced in gastric cancer tissues that were not associated with clinical features. Moreover, methylation of the promoters was reversely correlated with the expression. Following treatment with 5-aza-dc, AGS reduced cell viability and induced apoptosis, which is associated with upregulation of HHIP expression. The data demonstrated that loss of expression of HHIP and PTCH is associated with the methylation of gene promoters. In addition, 5-aza-dc-induced apoptosis correlated with the upregulation of HHIP expression in AGS. The findings demonstrated that the PTCH and HHIP genes may be novel targets for the control of gastric cancer.

  5. Using gastric juice lncRNA-ABHD11-AS1 as a novel type of biomarker in the screening of gastric cancer.

    PubMed

    Yang, Yunben; Shao, Yongfu; Zhu, Mengying; Li, Qier; Yang, Fang; Lu, Xuwen; Xu, Chunjing; Xiao, Bingxiu; Sun, Yanke; Guo, Junming

    2016-01-01

    Long noncoding RNAs (lncRNAs) play vital roles in tumorigenesis. However, the diagnostic values of most lncRNAs are largely unknown. To investigate whether gastric juice lncRNA-ABHD11-AS1 can be a potential biomarker in the screening of gastric cancer, 173 tissue samples and 130 gastric juice from benign lesion, gastric dysplasia, gastric premalignant lesions, and gastric cancer were collected. ABHD11-AS1 levels were detected by reverse transcription-polymerase chain reaction. Then, the relationships between ABHD11-AS1 levels and clinicopathological factors of patients with gastric cancer were investigated. The results showed that ABHD11-AS1 levels in gastric cancer tissues were significantly higher than those in other tissues. Its levels in gastric juice from gastric cancer patients were not only significantly higher than those from cases of normal mucosa or minimal gastritis, atrophic gastritis, and gastric ulcers but also associated with gender, tumor size, tumor stage, Lauren type, and blood carcinoembryonic antigen (CEA) levels. More importantly, when using gastric juice ABHD11-AS1 as a marker, the positive detection rate of early gastric cancer patients was reached to 71.4 %. Thanks to the special origin of gastric juice, these results indicate that gastric juice ABHD11-AS1 may be a potential biomarker in the screening of gastric cancer.

  6. 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

  7. 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

  8. Significance of serum markers pepsinogen I and II for chronic atrophic gastritis, peptic ulcer, and gastric cancer.

    PubMed

    Matsukura, N; Onda, M; Tokunaga, A; Fujita, I; Okuda, T; Mizutani, T; Kyono, S; Yamashita, K

    1993-01-01

    Chronic atrophic gastritis (CAG) is closely correlated with gastric cancer and is predominant in Japan. Epidemiologically, food habits are the primary factor in both CAG and gastric cancer. Two potential serum markers for CAG have recently been investigated, i.e., the concentration of serum pepsinogen (PG) and the presence of serum antibodies against Helicobacter pylori. Serum PG I and II and the PG I:PG II ratio have been reported to be useful as indicators of recurrent peptic ulcer and for screening of patients at risk from gastric cancer. In this study, we examined PG I and II in serum from 483 patients by RIA (DAINABOT), and endoscopic examination performed in the same patients before serological assay revealed CAG in 68, peptic ulcer in 91, and gastric cancer in 48. Analysis of the mean values according to patients age showed that CAG patients in their forties to eighties had low (< 40 ng/ml) levels of PG I, peptic ulcer patients in their teens to eighties had high (> or = 70 ng/ml) levels, except for those in their seventies, and gastric cancer patients in their twenties to sixties had low (< 3.0) PG I:PG II ratios, except for those in their sixties. Thus serum PG assay has potential utility for detection of CAG, peptic ulcer, and gastric cancer.

  9. The role of leptin in gastric cancer: clinicopathologic features and molecular mechanisms.

    PubMed

    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

    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.

  10. 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.

  11. Cellular aging and cancer

    PubMed Central

    Hornsby, Peter J.

    2010-01-01

    Aging is manifest in a variety of changes over time, including changes at the cellular level. Cellular aging acts primarily as a tumor suppressor mechanism, but also may enhance cancer development under certain circumstances. One important process of cellular aging is oncogene-induced senescence, which acts as an important anti-cancer mechanism. Cellular senescence resulting from damage caused by activated oncogenes prevents the growth or potentially neoplastic cells. Moreover, cells that have entered senescence appear to be targets for elimination by the innnate immune system. In another aspect of cellular aging, the absence of telomerase activity in normal tissues results in such cells lacking a telomere maintenance mechanism. One consequence is that in aging there is an increase in cells with shortened telomeres. In the presence of active oncogenes that cause expansion of a neoplastic clone, shortening of telomeres leading to telomere dysfunction prevents the indefinite expansion of the clone because the cells enter crisis. Crisis results from fusions and other defects caused by dysfunctional telomeres and is a terminal state of the neoplastic clone. In this way the absence of telomerase in human cells, while one cause of cellular aging, also acts as an anti-cancer mechanism. PMID:20705476

  12. 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

  13. Outlook on epigenetic therapeutic approaches for treatment of gastric cancer.

    PubMed

    Hudler, Petra

    2017-02-03

    The incidence of gastric cancer has been declining globally in the last decades. Despite the improvements in the diagnostic procedures, most cases are still detected at advanced stages due to lack of specific symptoms associated with early phases of tumour development. Consequently, gastric cancer poses a major health burden worldwide due to high mortality rates. Continuing advances in high-throughput technologies are revealing an intricate network of genetic and epigenetic changes associated with carcinogenesis. In addition, several risk factors, both environmental and genetic, have been recognized, which promote accumulation of diverse alterations affecting the expression of oncogenes, tumour suppressor genes, DNA repair genes, and other genes, implicated in normal gastric cell functions. A plethora of aberrant molecular events found in patients with this disease and intragenic heterogeneity of tumours from individuals are delaying the development of targeted biological therapies. Frequent occurrence of characteristic CpG island methylator phenotypes (CIMP phenotypes) in gastric cancers, particularly in association with Helicobacter pylori or EBV infection, could lead to introduction of epigenetic modulators into standard treatment regimens used against early and advanced forms of adenocarcinomas. This review highlights aberrant DNA methylation events in the development of gastric tumours and addresses the different aspects associated with the application of therapeutic epigenetic modulation in the management of the disease.

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

    PubMed

    Yuan, Wenzhen; Yang, Ning; Li, Xiangkai

    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.

  15. 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

  16. 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.

  17. The Synergism between Belotecan and Cisplatin in Gastric Cancer

    PubMed Central

    Jung, Joo Young; Song, Sang Hyun; Kim, Tae-Young; Park, Jung Hyun; Jong, Hyun-Soon; Im, Seock-Ah; Kim, Tae-You; Kim, Noe Kyoung

    2006-01-01

    Purpose We wanted to demonstrate the anti-cancer effect and interaction between belotecan and cisplatin on gastric cancer cell line and we evaluated the mechanisms of this synergistic effect in vitro. Materials and Methods The growth inhibitory effect of belotocan and cisplatin against several gastric cancer cell lines (SNU-5, SNU-16 and SNU-601) was estimated by tetrazolium dye assay. The effect of a combination treatment was evaluated by the isobologram method. The biochemical mechanisms for the interaction between the drugs were analyzed by measuring the formation of DNA interstrand cross-links (ICLs) and DNA topo-I activity. Results Belotecan showed synergism with cisplatin for growth inhibitory effect on the gastric cancer cell lines SNU-5, and SNU-16, but this was subadditive on the SNU-601 cell line. The formation of DNA ICLs in SNU-16 cells by cisplatin was increased by combination with belotecan, but this was not affected in SNU-601 cells. The topo-I inhibition by belotecan was enhanced at high concentrations of cisplatin in SNU-16, but not in SNU-601 cells. Conclusion Belotecan and cisplatin show various combination effect against gastric cancer cells. The synergism between cisplatin and belotecan could be the result of one of the following mechanisms: the modulating effect of belotecan on the repair of cisplatin-induced DNA adducts and the enhancing effect of cisplatin on the belotecan-induced topo-I inhibitory effect. PMID:19771277

  18. Chili pepper consumption and gastric cancer in Mexico: a case-control study.

    PubMed

    López-Carrillo, L; Hernández Avila, M; Dubrow, R

    1994-02-01

    Laboratory studies indicate that capsaicin, the hot-tasting component of chili peppers, may be carcinogenic. A population-based case-control study was conducted in Mexico City during 1989-1990 to evaluate the relation between chili pepper consumption and gastric cancer risk. The study included 220 incident cases and 752 controls randomly selected from the general population. Information was collected by interview. Chili pepper consumers were at high risk for gastric cancer compared with nonconsumers (age- and sex-adjusted odds ratio = 5.49, 95% confidence interval (CI) 2.72-11.06). Among consumers, there was a highly significant trend of increasing risk with increasing self-rated level of consumption (low, medium, and high) (p = 2 x 10(-7). The odds ratio for high-level consumers compared with nonconsumers was 17.11 (95% CI 7.78-37.59). However, when consumption was measured as frequency per day, a significant trend among consumers was not observed. Multivariable adjustment increased the magnitude of the chili pepper-gastric cancer association, but a significant trend among consumers (measured as frequency per day) was still not observed. Chili pepper consumption may be a strong risk factor for gastric cancer, but further studies are needed to test this hypothesis.

  19. A panel of autoantibodies against multiple tumor-associated antigens for detecting gastric cancer.

    PubMed

    Hoshino, Isamu; Nagata, Matsuo; Takiguchi, Nobuhiro; Nabeya, Yoshihiro; Ikeda, Atsushi; Yokoi, Sana; Kuwajima, Akiko; Tagawa, Masatoshi; Matsushita, Kazuyuki; Satoshi, Yajima; Hideaki, Shimada

    2017-01-08

    Gastric cancer is the second leading cause of cancer deaths in the world, and effective diagnosis is extremely important for good outcome. We assessed the diagnostic potential of an autoantibody panel that may provide a novel tool for the early detection of gastric cancer. We analyzed data from patients with gastric cancer and normal controls in a test and validation cohorts. Autoantibody levels were measured against a panel of six tumor-associated antigens [TAAs; p53, heat shock protein 70 (HSP70), HCC-22-5, peroxiredoxin VI (Prx VI), KM-HN-1, and p90 TAA (CYP2A)] via ELISA. We assessed serum autoantibodies in 100 participants in the test cohort. The validation cohort comprised 248 participants. Autoantibodies to at least one of the six antigens demonstrated a sensitivity/specificity of 49.0% [95% confidence interval (CI), 39.2-58.8%]/92.4% (95% CI, 87.2-97.6%) and 52.0% (95% CI, 42.2-61.8%)/90.5% (95% CI, 84.8-96.3%) in the test and validation cohorts, respectively. In the validation cohort, no significant differences were seen when patients were subdivided based on age, sex, depth of tumor invasion, lymph node metastasis, distant metastasis, peritoneal dissemination, and TNM stage. Patients who were positive for more than two antibodies in the panel tended to have a worse prognosis than those who were positive for one or no antibody. Measurement of autoantibody response to multiple TAAs in an optimized panel assay to discriminate patients with early stage gastric cancer from normal controls may aid in the early detection of gastric cancer. This article is protected by copyright. All rights reserved.

  20. Serum Helicobacter pylori NapA antibody as a potential biomarker for gastric cancer.

    PubMed

    Liu, Jingjing; Liu, Huimin; Zhang, Tingting; Ren, Xiyun; Nadolny, Christina; Dong, Xiaoqun; Huang, Lina; Yuan, Kexin; Tian, Wenjing; Jia, Yunhe

    2014-02-20

    Helicobacter pylori (H. pylori) infection is strongly associated with gastric cancer. However, only a minority of infected individuals ever develop gastric cancer. This risk stratification may be in part due to differences among strains. The relationship between neutrophil-activating protein (NapA) and gastric cancer is unclear. The purpose of this study is to evaluate the significance of NapA as a biomarker in gastric cancer. We used enzyme linked immunosorbent assay (ELISA) to determine the status of H. pylori infection. Indirect ELISA method was used for detection of NapA antibody titer in the serum of H. pylori infected individuals. Unconditional logistic regressions were adopted to analyze the variables and determine the association of NapA and gastric cancer. The results of study indicated serum H. pylori NapA antibody level were associated with a reduced risk for development of gastric cancer. It may be used in conjugation with other indicators for gastric cancer detection.

  1. State-of-the-art preoperative staging of gastric cancer by MDCT and magnetic resonance imaging

    PubMed Central

    Choi, Joon-Il; Joo, Ijin; Lee, Jeong Min

    2014-01-01

    Gastric cancer is one of the most common and fatal cancers. The importance of accurate staging for gastric cancer has become more critical due to the recent introduction of less invasive treatment options, such as endoscopic mucosal resection or laparoscopic surgery. The tumor-node-metastasis staging system is the generally accepted staging system for predicting the prognosis of patients with gastric cancer. Multidetector row computed tomography (MDCT) is a widely accepted imaging modality for the preoperative staging of gastric cancer that can simultaneously assess locoregional staging, including the gastric mass, regional lymph nodes, and distant metastasis. The diagnostic performance of MDCT for T- and N-staging has been improved by the technical development of isotropic imaging and 3D reformation. Although magnetic resonance imaging (MRI) was not previously used to evaluate gastric cancer due to the modality’s limitations, the development of high-speed sequences has made MRI a feasible tool for the staging of gastric cancer. PMID:24782607

  2. 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

  3. Successful endoscopic submucosal dissection for early gastric cancer adjacent to gastric cardia varix

    PubMed Central

    Watanabe, Ko; Hikichi, Takuto; Nakamura, Jun; Takagi, Tadayuki; Suzuki, Rei; Sugimoto, Mitsuru; Waragai, Yuichi; Kikuchi, Hitomi; Konno, Naoki; Asama, Hiroyuki; Takasumi, Mika; Watanabe, Hiroshi; Obara, Katsutoshi; Ohira, Hiromasa

    2016-01-01

    Abstract A 58-year-old man with liver cirrhosis and renal failure was diagnosed with esophageal varices (EVs) and a gastric cardia varix (GCV) by esophagogastroduodenoscopy (EGD). The patient also exhibited early gastric cancer (EGC) in the upper gastric body adjacent to the GCV. The EVs and GCV were treated using endoscopy before endoscopic submucosal dissection (ESD) of the EGC to prevent variceal bleeding during ESD. Endoscopic variceal ligation (EVL) was performed to treat the EVs. In addition, extra-variceal polidocanol injection and argon plasma coagulation (APC) were performed after EVL. Follow-up EGD two months after APC revealed that the GCV had diminished in size. Then, ESD was performed with polidocanol injection into the submucosa around the GCV to prevent bleeding. During ESD, the EGC was resected en bloc without severe bleeding. Complications were not observed after ESD. Histopathological examination of the ESD specimens indicated that the resection was curative. PMID:27477990

  4. A case of gastric adenocarcinoma in a Shih Tzu dog: successful treatment of early gastric cancer.

    PubMed

    Lee, Hee-Chun; Kim, Ji-Hyun; Jee, Cho-Hee; Lee, Jae-Hoon; Moon, Jong-Hyun; Kim, Na-Hyun; Sur, Jung-Hyang; Cho, Kyu-Woan; Kang, Byeong-Teck; Ha, Jeongim; Jung, Dong-In

    2014-07-01

    A 9-year-old castrated male Shih Tzu dog was referred to us, because of chronic vomiting. The patient's hematological, radiographic, ultrasonographic, endoscopic and histological examinations were evaluated for diagnosis. Hematologic analysis indicated moderate anemia and azotemia. Based on the imaging studies, an oval-shaped mass was identified in the gastric pylorus area. A proliferative mass was found on endoscopic examination, and we performed biopsy using grasping forceps. The histopathological findings of the biopsy specimens indicated hypertrophic gastritis, and Y-U pyloroplasty was performed. However, histopathological examination of the surgically resected mass revealed tubular adenocarcinoma of the stomach. Then, carboplatin chemotherapy was performed 4 times for 13 weeks. Clinical signs, such as vomiting, were resolved gradually after surgery and chemotherapy, and the patient's condition was managed favorably until recently (30 months after surgery). This case report describes clinical features, imaging studies, endoscopic characteristics and histopathological and immunohistochemical features of gastric tubular adenocarcinoma as early gastric cancer in a dog.

  5. Hereditary diffuse gastric cancer: updated consensus guidelines for clinical management and directions for future research.

    PubMed

    Fitzgerald, Rebecca C; Hardwick, Richard; Huntsman, David; Carneiro, Fatima; Guilford, Parry; Blair, Vanessa; Chung, Daniel C; Norton, Jeff; Ragunath, Krishnadath; Van Krieken, J Han; Dwerryhouse, Sarah; Caldas, Carlos

    2010-07-01

    25-30% of families fulfilling the criteria for hereditary diffuse gastric cancer have germline mutations of the CDH1 (E-cadherin) gene. In light of new data and advancement of technologies, a multidisciplinary workshop was convened to discuss genetic testing, surgery, endoscopy and pathology reporting. The updated recommendations include broadening of CDH1 testing criteria such that: histological confirmation of diffuse gastric criteria is only required for one family member; inclusion of individuals with diffuse gastric cancer before the age of 40 years without a family history; and inclusion of individuals and families with diagnoses of both diffuse gastric cancer (including one before the age of 50 years) and lobular breast cancer. Testing is considered appropriate from the age of consent following counselling and discussion with a multidisciplinary team. In addition to direct sequencing, large genomic rearrangements should be sought. Annual mammography and breast MRI from the age of 35 years is recommended for women due to the increased risk for lobular breast cancer. In mutation positive individuals prophylactic total gastrectomy at a centre of excellence should be strongly considered. Protocolised endoscopic surveillance in centres with endoscopists and pathologists experienced with these patients is recommended for: those opting not to have gastrectomy, those with mutations of undetermined significance, and in those families for whom no germline mutation is yet identified. The systematic histological study of prophylactic gastrectomies almost universally shows pre-invasive lesions including in situ signet ring carcinoma with pagetoid spread of signet ring cells. Expert histopathological confirmation of these early lesions is recommended.

  6. Telomere length shortening in gastric mucosa is a field effect associated with increased risk of gastric cancer.

    PubMed

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

    2016-07-01

    Telomere shortening occurs in many organs and tissues and is accelerated by oxidative injury and rapid cell turnover. Short telomeres initiate chromosomal instability and may eventually contribute to tumorigenesis. To evaluate telomere length as potential biomarker for gastric cancer (GC) risk, we measured average telomere length using quantitative real-time PCR in GC tissues and in non-neoplastic mucosa from patients with GC and without GC. We obtained of 217 GC patients matched biopsies from the GC and adjacent tissues as well as gastric biopsies of 102 subjects without GC. Relative telomere length was measured in genomic DNA by real-time PCR. Relative telomere length decreased gradually in Helicobacter pylori (H. pylori) negative and positive gastric mucosa of GC free subjects compared with adjacent mucosa and cancer tissue from GC patients (4.03 ± 0.3 vs. 2.82 ± 0.19 vs. 0.82 ± 0.07 vs. 0.29 ± 0.09, P < 0.0001). In non-neoplastic mucosa of GC patients, shorter telomeres were found significantly more often than in that of GC free subjects (age, sex, and H. pylori adjusted odds ratio = 7.81, 95 % confidence interval = 4.71-12.9, P < 0.0001). Telomere shortening in non-neoplastic mucosa was associated with chronic inflammation (P = 0.0018) and intestinal metaplasia (P < 0.0001). No significant associations were found between relative telomere length and clinicopathological features of GC and overall survival. Telomere shortening in gastric mucosa reflects a field effect in an early stage of carcinogenesis and is associated with an increased risk of GC. Telomere length in GC is not associated with clinicopathological features or prognosis.

  7. Impact of NPR-A expression in gastric cancer cells

    PubMed Central

    Zhang, Jia; Qu, Jingkun; Yang, Ya; Li, Min; Zhang, Mingxin; Cui, Xiaohai; Zhang, Jing; Wang, Jiansheng

    2014-01-01

    Background: The receptors for the cardiac hormone atrial natriuretic peptide (ANP), natriuretic peptide receptor A (NPR-A), have been reported to be expressed in lung cancer, prostate cancer, ovarian cancer. NPR-A expression and signaling is important for tumor growth, its deficiency protect C57BL/6 mice from lung, skin, and ovarian cancers, and these result suggest that NPR-A is a new target for cancer therapy. Recently, NPR-A has been demonstrated to be expressed in pre-implantation embryos and in ES cells, it has a novel role in the maintenance of self-renewal and pluripotency of ES cells. However, the direct role of NPR-A signaling in gastric cancer remains unclear. Method: NPR-A expression was downregulated by transfection of shRNA. The proliferation of gastric cancer cells was measured by Hoechst 33342 stain. Cell proliferation and invasion were determined via BrdU and transwell assays, respectively. Results: Down-regulation of NPR-A expression by shNPR-A induced apoptosis, inhibited proliferation and invasion in AGS cells. The mechanism of shNPR-A-induced anti-AGS effects was linked to NPR-A-induced expression of KCNQ1, a gene to be overexpressed in AGS and significantly reduced by shNPR-A. Conclusion: Collectively, these results suggest that NPR-A promotes gastric cancer development in part by regulating KCNQ1. Our findings also suggest that NPR-A is a target for gastric cancer therapy. PMID:25419351

  8. FGF19 Contributes to Tumor Progression in Gastric Cancer by Promoting Migration and Invasion.

    PubMed

    Wang, Shuang; Zhao, Daqi; Tian, Ruihua; Shi, Hailong; Chen, Xiangming; Liu, Wenzhi; Wei, Lin

    2016-01-01

    Gastric cancer is the fourth most common type of cancer and second leading cause of cancer-related death in the world. Since patients are often diagnosed at a late stage, very few effective therapies are left in the arsenal. FGF19, as a hormone, has been reported to promote tumor growth in various types of cancer; however, its function in gastric cancer remains unknown. In the current study, we showed that FGF19 is overexpressed in gastric cancer and is associated with depth of invasion, lymph node metastasis, and TNM stage. In addition, in vitro experiments demonstrated that FGF19 is able to enhance migration and invasion abilities of gastric cancer cells. Given its great potency in gastric cancer progression, FGF19 may be an effective target of treatment for advanced gastric cancer patients.

  9. Geographical distribution of the incidence of gastric cancer in Bhutan

    PubMed Central

    Dendup, Tashi; Richter, James M; Yamaoka, Yoshio; Wangchuk, Kinley; Malaty, Hoda M

    2015-01-01

    AIM: To estimate the prevalence of gastric cancer (GC) in a cohort of patients diagnosed with GC and to compare it with patients diagnosed with all other types of gastro-intestinal (GI) cancer during the same period. METHODS: Between 2008 and 2013, five-year period, the medical records of all GI cancer patients who underwent medical care and confirm diagnosis of cancer were reviewed at the National Referral Hospital, Thimphu which is the only hospital in the country where surgical and cancer diagnosis can be made. Demographic information, type of cancer, and the year of diagnosis were collected. RESULTS: There were a total of 767 GI related cancer records reviewed during the study period of which 354 (46%) patients were diagnosed with GC. There were 413 patients with other GI cancer including; esophagus, colon, liver, rectum, pancreas, gall bladder, cholangio-carcinoma and other GI tract cancers. The GC incidence rate is approximately 0.9/10000 per year (367 cases/5 years per 800000 people). The geographic distribution of GC was the lowest in the south region of Bhutan 0.3/10000 per year compared to the central region 1.4/10000 per year, Eastern region 1.2/10000 per year, and the Western region 1.1/10000 per year. Moreover, GC in the South part was significantly lower than the other GI cancer in the same region (8% vs 15%; OR = 1.8, 95%CI: 1.3-3.1, P = 0.05). Among GC patients, 38% were under the age of 60 years, mean age at diagnosis was 62.3 (± 12.1) years with male-to-female ratio 1:0.5. The mean age among patients with all other type GI cancer was 60 years (± 13.2) and male-to-female ratio of 1:0.7. At time of diagnosis of GC, 342 (93%) were at stage 3 and 4 of and by the year 2013; 80 (23%) GC patients died compared to 31% death among patients with the all other GI cancer (P = 0.08). CONCLUSION: The incidence rate of GC in Bhutan is twice as high in the United States but is likely an underestimate rate because of unreported and undiagnosed cases in the

  10. [Mass screening for gastric cancer performed in Costa Rica].

    PubMed

    Sasagawa, Yumiko; Sasagawa, Tsuyoshi; Takasaki, Ken

    2002-06-01

    We performed mass screening for gastric cancer by means of X-ray in Costa Rica from 1996 through 1999. Screening was performed on 10,064 subjects and 69 gastric cancers were detected (screening group). During the same period 172 gastric cancer patients were referred to us (non-screening group). Results of screening in Japan (Japanese group) were quoted from the annual report of the Japanese Society of Gastroenterological Mass Survey. This study is a comparison of these 3 groups. The detection rate was 0.68% in the screening group, 0.11% in the Japanese group. The operability was 92.7%, 76.1%, 97.0%, the resectability 96.8%, 83.2%, 98.6%, the rate of early gastric cancer 64.5%, 30.3%, 65.9%, and the rate of curability A 79.0%, 38.5%. 82.6% in the screening group, non-screening group and Japanese group respectively. The results in the screening group were exactly equal to those in the Japanese group. These results show that the same results can be obtained in Costa Rica as in Japan, if screening is performed with the same diagnostic level and skill as in Japan.

  11. 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

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

    PubMed

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

    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.

  13. 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.

  14. The recession of gastric cancer and its possible causes.

    PubMed

    Seely, S

    1978-01-01

    The paper re-examines the hypothesis that excessively hot drinks constitute an important risk factor in the causation of gastric cancer. The recession of gastric cancer mortality rates in the United States in recent decades is attributed to dietary changes tending to supplant the traditional hot beverages. One such change was the appearance of domestic refrigerators, promoting iced drinks, another the popularisation of soft drinks. The example of Okinawa is quoted where in 1972, after 27 years of American administration, gastric cancer mortality rate was 11.3 per 100,000, in contrast to Japan's 46.7, presumably due to the introduction of American dietary habits. While in most Western European countries gastric cancer risk decreased in the last decades, there was little change in Eastern Europe, and rates were rising in some countries, like Portugal, Mexico and Hong-Kong. This is attributed to the increasing pollution of water, promoting its boiling and flovouring. In some countries water is disinfected by chlorination in which case boiling and flavouring may be used to mask the unpleasant smell and taste of disinfectant.

  15. Dietary salt intake and risk of gastric cancer.

    PubMed

    D'Elia, Lanfranco; Galletti, Ferruccio; Strazzullo, Pasquale

    2014-01-01

    Humans began to use large amounts of salt for the main purpose of food preservation approximately 5,000 years ago and, although since then advanced technologies have been developed allowing drastic reduction in the use of salt for food storage, excess dietary salt intake remains very common. Gastric cancer is a common neoplasia, and dietary factors, including salt consumption, are considered relevant to its causation. A number of experimental studies supported the cocarcinogenic effect of salt through synergic action with Helicobacter pylori infection, in addition to some independent effects such as increase in the rate of cell proliferation and of endogenous mutations. Many epidemiological studies analyzed the relationship between excess salt intake and risk of gastric cancer. Both cross-sectional and prospective studies indicated a possibly dose-dependent positive association. In particular, a comprehensive meta-analysis of longitudinal studies detected a strong adverse effect of total salt intake and salt-rich foods on the risk of gastric cancer in the general population. Altogether, the epidemiological, clinical, and experimental evidence supports the possibility of a substantial reduction in the rates of gastric cancer through progressive reduction in population salt intake.

  16. 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

  17. 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.

  18. Applications of nanotechnology in gastric cancer: detection and prevention by nutrition.

    PubMed

    Elingarami, Sauli; Liu, Ming; Fan, Jing; He, Nongyue

    2014-01-01

    New and emerging technologies, such as nanotechnology, have the potential to advance nutrition science by assisting in the discovery, development, and delivery of several intervention strategies to improve health and reduce the risk and complications of several diseases, including gastric cancer. This article reviews gastric cancer in relation to nutrition, discussing gastric carcinogenesis in-depth in relation to prevention of the disease by nutrition, as well as current detection approaches using nanotechnology. The current status of molecular nutritional biomarkers for gastric cancer is also discussed, as well as future strategies for the tailored management of gastric cancer.

  19. From inflammation to gastric cancer: Role of Helicobacter pylori

    PubMed Central

    Zhang, Xiao-Ying; Zhang, Pei-Ying; Aboul-Soud, Mourad A.M.

    2017-01-01

    Gastric cancer is a multifactorial disease and a leading cause of mortality and the risk factors for this include environmental factors and factors that influence host-pathogen interaction and complex interplay between these factors. Gastric adenocarcinomas are of two types, namely intestinal and diffuse type, and Helicobacter pylori (H. pylori) infection has been suspected of being causally linked to the initiation of chronic active gastritis, which leads to adenocarcinoma of the intestinal type. Even though most individuals with H. pylori infection do not show any clinical symptoms, long-term infection leads to inflammation of gastric epithelium and approximately 10% of infected patients develop peptic ulcers and 1–3% of patients develop gastric adenocarcinoma. Among the several mechanisms involved in tumorigenesis, CagA and peptidoglycan of H. pylori, which enter the infected gastric epithelial cells play an important role by triggering oncogenic pathways. Inflammation induced by H. pylori in gastric epithelium, which involves the cyclooxygenase-2/prostaglandin E2 pathway and IL-1β, is also an important factor that triggers chronic active gastritis and adenocarcinoma. H. pylori infection induced oxidative stress and dysregulated E-cadherin/β-catenin/p120 interactions and function also play a critical role in tumorigenesis. Environmental and dietary factors, in particular salt intake, are known to modify the pathogenesis induced by H. pylori. Gastric cancer induced by H. pylori appears to involve several mechanisms, making this mode of tumorigenesis a highly complicated process. Nevertheless, there are many events in this tumorigenesis that remain to be clarified and investigated. PMID:28356927

  20. Omission of breakfast and risk of gastric cancer in Mexico

    PubMed Central

    Verdalet-Olmedo, Monserrat; Sampieri, Clara Luz; Morales-Romero, Jaime; Montero-L de Guevara, Hilda; Machorro-Castaño, Álvaro Manuel; León-Córdoba, Kenneth

    2012-01-01

    AIM: To investigate factors associated with gastric cancer (GC) in the Mexican population using a validated questionnaire. METHODS: We designed and validated in Spanish a Questionnaire to Find Factors Associated with Diseases of the Digestive Tract using GC as a model. A cross-sectional study using 49 subjects, with confirmed histopathological GC diagnosis, and 162 individuals without GC participated. Odds ratio and 95% CIs were estimated in univariate and multivariate analysis adjusted for possible confounding factors. In order to match age groups, a multivariate sub-analysis was performed in subjects ≥ 39 years of age and in females and males separately. RESULTS: In the univariate analysis, we found an association between GC and education to primary level or below, low socioeconomic status, the use of dental prostheses, omission of breakfast, consumption of very hot food and drink, addition of salt to prepared foods, consumption of salt-preserved foods and the pattern of alcohol consumption. We found protection against GC associated with the use of mouthwash, food refrigeration and regular consumption of fruit and vegetables. In the multivariate sub-analysis with subjects of ≥ 39 years, the omission of breakfast was identified as a risk factor for GC. CONCLUSION: Our study suggests an association between the omission of breakfast and the failure to refrigerate food with GC in the Mexican population. PMID:23444276

  1. Expression of aurora kinase A correlates with the Wnt-modulator RACGAP1 in gastric cancer.

    PubMed

    Bornschein, Jan; Nielitz, Jessica; Drozdov, Ignat; Selgrad, Michael; Wex, Thomas; Jechorek, Doerthe; Link, Alexander; Vieth, Michael; Malfertheiner, Peter

    2016-03-01

    Canonical Wnt signaling is involved in gastric carcinogenesis. The aim of this study was to identify the link between Wnt signaling and aurora kinase A (AURKA), a target for the treatment of gastrointestinal cancers. Publicly available microarray data were used to identify phenotype-specific protein-protein interaction (PPI) subnetworks. The in silico analysis revealed a gastric cancer-specific PPI subnetwork consisting of 2745 proteins and 50,935 interactions. We focused on the link of AURKA to a Wnt-specific interaction module consisting of 92 proteins. There was a direct association of AURKA with Rac GTPase-activating protein 1 (RACGAP1), as well as with CTNBB1 (β-catenin) and CDKN1A as second-order interactors. Differential expression analysis revealed a significant downregulation of both AURKA and RACGAP1 in gastric cancer compared to noncancer controls. Biopsies from a prospective cohort of 56 patients with gastric cancer (32 intestinal type, 24 diffuse type) and 20 noncancer controls were used for validation of the identified targets. The RT-PCR data confirmed a strong correlation of AURKA and RACGAP1 gene expression both in the tumor, the tumor-adjacent and the tumor-distant mucosa. RACGAP1 in the tumor was also associated with CTNBB1 expression, and inversely associated with CDKN1A gene expression. Immunohistochemistry confirmed expression of the RACGAP1 protein in gastric cancer and the tumor-adjacent mucosa. RACGAP1 expression was not associated with tumor stage, grading, Lauren type, Helicobacter pylori infection, or age. In conclusion, AURKA is directly associated with the expression of RACGAP1, a modulator of the canonical Wnt signaling pathway.

  2. Loss of the coxsackie and adenovirus receptor contributes to gastric cancer progression

    PubMed Central

    Anders, M; Vieth, M; Röcken, C; Ebert, M; Pross, M; Gretschel, S; Schlag, P M; Wiedenmann, B; Kemmner, W; Höcker, M

    2009-01-01

    Loss of the coxsackie and adenovirus receptor (CAR) has previously been observed in gastric cancer. The role of CAR in gastric cancer pathobiology, however, is unclear. We therefore analysed CAR in 196 R0-resected gastric adenocarcinomas and non-cancerous gastric mucosa samples using immunohistochemistry and immunofluorescence. Coxsackie and adenovirus receptor was found at the surface and foveolar epithelium of all non-neoplastic gastric mucosa samples (n=175), whereas only 56% of gastric cancer specimens showed CAR positivity (P<0.0001). Loss of CAR correlated significantly with decreased differentiation, increased infiltrative depths, presence of distant metastases, and was also associated with reduced carcinoma-specific survival. To clarify whether CAR impacts the tumorbiologic properties of gastric cancer, we subsequently determined the role of CAR in proliferation, migration, and invasion of gastric cancer cell lines by application of specific CAR siRNA or ectopic expression of a human full-length CAR cDNA. These experiments showed that RNAi-mediated CAR knock down resulted in increased proliferation, migration, and invasion of gastric cancer cell lines, whereas enforced ectopic CAR expression led to opposite effects. We conclude that the association of reduced presence of CAR in more severe disease states, together with our findings in gastric cancer cell lines, suggests that CAR functionally contributes to gastric cancer pathogenesis, showing features of a tumour suppressor. PMID:19142187

  3. Reproductive factors and risk of oesophageal and gastric cancer in the Million Women Study cohort

    PubMed Central

    Green, J; Roddam, A; Pirie, K; Kirichek, O; Reeves, G; Beral, V

    2012-01-01

    Background: Hormonal factors may influence risk for upper gastrointestinal cancers in women. We examined risk of oesophageal and gastric cancers in relation to reproductive factors in a large UK cohort, the Million Women Study. Methods: Among 1 319 409 women aged on average 56 years at recruitment, 1186 incident cancers of the oesophagus and 1194 of the stomach were registered during 11.9 million person-years' observation. Adjusted relative risks (RRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models. Results: Risks of both oesophageal and gastric cancer were significantly higher in postmenopausal than in pre- or peri-menopausal women (RRs 1.46, 1.07–2.00 and 1.59, 1.15–2.20, respectively; P⩽0.01 for both); and, among postmenopausal women, risk was higher the younger women were at menopause (RR, 95% CI per 5 years younger at menopause 1.18, 1.05–1.34 for oesophageal cancer and 1.18, 1.04–1.34 for stomach cancer, Ptrend=0.01 for both). For factors relating to childbearing, including women's age at first birth, their number of children, and breastfeeding history, the only significant association was a higher risk of oesophageal cancer in nulliparous, compared with parous, women (RR 1.31, 1.11–1.55; P=0.002). When risks for squamous cell and adenocarcinomas of the oesophagus were compared, most did not differ significantly, but statistical power was limited. Conclusion: Both oesophageal and gastric cancer risks appeared to be related to menopausal status and age at menopause, but there was little consistent evidence for associations with factors related to childbearing. PMID:22127287

  4. Distal gastrectomy versus total gastrectomy for distal gastric cancer

    PubMed Central

    Liu, Zhen; Feng, Fan; Guo, Man; Liu, Shushang; Zheng, Gaozan; Xu, Guanghui; Lian, Xiao; Fan, Daiming; Zhang, Hongwei

    2017-01-01

    Abstract Even though more than a century later, after the first case of gastrectomy has been successfully performed, the best surgical treatment for distal gastric cancer still remains controversial. Thus, the present study was designed to compare the survival impact of distal (DG) or total gastrectomy (TG) for distal gastric cancer. A total of 1262 distal gastric cancer patients were enrolled in current study including 1157 patients who underwent DG and 157 patients who underwent TG. The postoperative complications and 5-year overall survival were compared between the 2 groups. TG group presented a longer surgical time, a higher volume of intraoperative bleeding, and a larger number of excised lymph nodes (all P < 0.05) compared with the DG group. The postoperative complications were comparable (all P >0.05). The 5-year overall survival rate of DG group was significantly higher than that of TG group (67.6% vs 44.3%, P < 0.001). However, multivariate analysis showed that type of resection was not an independent prognostic factor for distal gastric cancer (P > 0.05). The factor-stratified multivariate analysis showed that only in the subgroup of Tumor-node-metastasis staging system (TNM) stage III (P = 0.049), TG was the independent prognostic factor for poor survival. In conclusion, DG was as feasible as TG; however, TG did not increase the survival rate. DG brought better long-term survival than TG in patients with TNM stage III tumor. We recommended that DG should be the optimal surgical procedure for distal gastric cancer under the premise of negative resection margin. PMID:28151896

  5. NHE1 is upregulated in gastric cancer and regulates gastric cancer cell proliferation, migration and invasion.

    PubMed

    Xie, Rui; Wang, Haibo; Jin, Hai; Wen, Guorong; Tuo, Biguang; Xu, Jingyu

    2017-03-01

    Na+/H+ exchanger isoform 1 (NHE1) is known to play a key role in regulating intracellular pH and osmotic homeostasis and is involved in the development and progression of several types of cancer. However, the function and specific mechanism of NHE1 in gastric cancer (GC) are not clearly understood. In the present study, we report that NHE1 is overexpressed in tissues and cell lines from GC patients, and knockdown or inhibition of NHE1 suppressed GC cell proliferation via regulation of G1/S and G2/M cell cycle phase transitions, concomitant with a marked decrease in positive cell cycle regulators, including cyclin D1 and cyclin B1. Likewise, NHE1 was required for GC cell migration and invasion through the regulation of epithelial-mesenchymal transition (EMT) proteins, and NHE1 inhibition resulted in an acidic intracellular environment, providing possible mechanisms underlying NHE1-mediated GC progression both in vitro and in vivo. These data highlight the important role of NHE1 in GC progression and suggest that NHE1 may be a useful target for GC therapy.

  6. Serological response to Helicobacter pylori infection among Latin American populations with contrasting risks of gastric cancer

    PubMed Central

    Camargo, M. Constanza; Beltran, Mauricio; Conde-Glez, Carlos; Harris, Paul R.; Michel, Angelika; Waterboer, Tim; Flórez, Astrid Carolina; Torres, Javier; Ferreccio, Catterina; Sampson, Joshua N.; Pawlita, Michael; Rabkin, Charles S.

    2015-01-01

    Gastric cancer is a rare outcome of chronic Helicobacter pylori infection. Serologic profiles may reveal bacterial, environmental and/or host factors associated with cancer risk. We therefore compared specific anti-H. pylori antibodies among populations with at least 2-fold differences in gastric cancer mortality from Mexico, Colombia and Chile. Our study included 1,776 adults (mean age 42 years) from three nationally representative surveys, equally divided between residents of high- and low-risk areas. Antibodies to 15 immunogenic H. pylori antigens were measured by fluorescent bead-based multiplex assays; results were summarized to identify overall H. pylori seropositivity. We used logistic regression to model associations between antibody seroreactivity and regional cancer risk (high vs. low), adjusting for country, age and sex. Both risk areas had similar H. pylori seroprevalence. Residents in high- and low-risk areas were seroreactive to a similar number of antigens (means 8.2 vs. 7.9, respectively; adjusted-odds ratio, OR: 1.02, p=0.05). Seroreactivities to Catalase and the known virulence proteins CagA and VacA were each significantly (p<0.05) associated with residence in high-risk areas, but ORs were moderate (1.26, 1.42, and 1.41, respectively) and their discriminatory power was low (ROC area under curve <0.6). The association of Catalase was independent from effects of either CagA or VacA. Sensitivity analyses for antibody associations restricted to H. pylori-seropositive individuals generally replicated significant associations. Our findings suggest that humoral responses to H. pylori are insufficient to distinguish high and low gastric cancer risk in Latin America. Factors determining population variation of gastric cancer burden remain to be identified. PMID:26178251

  7. 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.

  8. Ataxin-3 expression correlates with the clinicopathologic features of gastric cancer

    PubMed Central

    Zeng, Li-Xia; Tang, Yong; Ma, Yun

    2014-01-01

    To investigate the expression of Ataxin-3 in human gastric cancer tissues and cell lines, and explore its clinical pathologic significance. Methods: The expression of Ataxin-3 in gastric cancer (n=536) and noncancerous gastric mucosa (n=312) was determined by immunohistochemistry and correlated to clinicopathologic features such as histologic differentiation and tumor size. The expression of Ataxin-3 protein in the human gastric cancer cell lines MKN45, SGC7901 and in normal human gastric epithelial cells (GES-1) was also evaluated by Western blot analysis. Quantitative real-time PCR was used to determine Ataxin-3 mRNA expression in human gastric cancer cell lines and tissues. Results: The expression of Ataxin-3 protein was decreased in the gastric cancer compared to noncancerous gastric tissue, and correlated with tumor size, Lauren classification, histologic differentiation, and mutant p53 protein (P < 0.05). Similarly, Ataxin-3 mRNA expression was decreased in the gastric cancers compared to the noncancerous gastric tissue. Ataxin-3 protein and mRNA expression was lower in MKN45, SGC7901 cells than in the normal GES-1 cells. Conclusion: Decreased expression of Ataxin-3 may play an important role in gastric carcinogenesis and development of gastric cancer. PMID:24955170

  9. 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

  10. Inhibition of sphingosine-1-phosphate phosphatase 1 promotes cancer cells migration in gastric cancer: Clinical implications.

    PubMed

    Gao, Xiang Y; Li, Lin; Wang, Xiao H; Wen, Xian Z; Ji, Ke; Ye, Lin; Cai, Jun; Jiang, Wen G; Ji, Jia F

    2015-10-01

    Sphingosine-1-phosphate (S1P) plays an important role in regulating many biological processes. Sphingosine-1-phosphate phosphatase 1 (SGPP1) can dephosphorylate S1P into sphingosine and tip the balance of sphingosine-S1P. Increased levels of sphingosine leads to a decrease in the ability of cell invasion as well as an increase in the ability of cell apoptosis. However, little is known regarding the effects of SGPP1 in gastric cancer. The present study examined the function of SGPP1 on gastric cancer cell lines as well as its clinical relevance in gastric cancer progression. Using immunohistochemistry and RT-qPCR techniques, the clinical significance of SGPP1 expression was analyzed in 288 paraffin-embedded gastric tissue specimens and 219 fresh gastric tissues, respectively. Transgenes encoding ribozymes to specifically target human SGPP1 (pEF-SGPP1) was constructed. Human gastric cancer cell lines (AGS and HGC27) were transfected with pEF-SGPP1 transgene and examined by functional analysis. SGPP1 was downregulated in gastric cancer tissues, compared with adjacent normal gastric tissues (p=0.034). SGPP1 mRNA levels in gastric cancer tissues were significantly decreased when compared with their adjacent non-cancerous tissues (p<0.001). Weakly expressed SGPP1 was positively correlated with the lymph node metastasis (p=0.005) and distant metastasis (p=0.031). Kaplan-Meier survival curves revealed that patients with SGPP1 positive expression had a significant increase in overall survival (OS) (p=0.034) and progression-free survival (PFS) (p=0.041). Multivariate analysis indicated the expression of SGPP1 was an independent prognostic factor in gastric cancer patients (p=0.041). In vitro experiments showed that knockdown of SGPP1 resulted in an increase in the invasion (2-fold) and migration (5-fold) of AGS and HGC27. The two gastric cancer cells transfected with pEF-SGPP1 exhibited a slower rate of growth with less adhesion. Thus, our findings provided evidence that

  11. Gastric perforation secondary to metastasis from breast cancer.

    PubMed

    Wong, Chee Siong; Gumber, Ashutosh; Kiruparan, Pasupathy; Blackmore, Alexander

    2016-07-18

    Gastric perforation secondary to metastasis from breast cancer occurs infrequently. We present the case of a 72-year-old postmenopausal female patient with a known history of lobular carcinoma of the breast who presented to a district general hospital with a clinical diagnosis of an acute abdomen. Further contrast-enhanced CT scan demonstrated free gas and fluid in the abdomen. She underwent emergency exploratory laparotomy and onlay Graham's omentopexy patch due to 1×1 cm prepyloric gastric perforation. Final histopathology proved the presence of metastatic malignant cells in the breast origin. We discuss the issues involved in postoperative investigation and management.

  12. Prognostic significance of CD44 in human colon cancer and gastric cancer: Evidence from bioinformatic analyses

    PubMed Central

    Xia, Pu; Xu, Xiao-Yan

    2016-01-01

    CD44 is a well-recognized stem cell biomarker expressed in colon and gastric cancer. In order to identify whether CD44 mRNA could be used as a prognostic marker in colon and gastric cancer, bioinformatic analyses were used in this study. cBioPortal analysis and COSMIC analysis were used to explore the CD44 mutation. CD44 mRNA levels were evaluated by using SAGE Genie tools and Oncomine analysis. Kaplan-Meier Plotter was performed to identify the prognostic roles of CD44 mRNA in these two cancers. In this study, first, we found that low alteration frequency of CD44 mRNA in colon and gastric cancer. Second, the high CD44 mRNA level was found in colon and gastric cancer, and it correlated with a benign survival rate in gastric cancer. Third, CD4 and CD74 may be used as markers to predict the prognosis of colon and gastric cancer. However, the deep mechanism(s) of these results remains unclear, further studies have to be performed in the future. PMID:27323782

  13. Current status in remnant gastric cancer after distal gastrectomy.

    PubMed

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

    2016-02-28

    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.

  14. 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

  15. Aberrant expression of Cx43 is associated with the peritoneal metastasis of gastric cancer and Cx43-mediated gap junction enhances gastric cancer cell diapedesis from peritoneal mesothelium.

    PubMed

    Tang, Bo; Peng, Zhi-hong; Yu, Pei-wu; Yu, Ge; Qian, Feng; Zeng, Dong-zhu; Zhao, Yong-liang; Shi, Yan; Hao, Ying-xue; Luo, Hua-xing

    2013-01-01

    The process of peritoneal metastasis involves the diapedesis of intra-abdominal exfoliated gastric cancer cells through the mesothelial cell monolayers; however, the related molecular mechanisms for this process are still unclear. Heterocellular gap-junctional intercellular communication (GJIC) between gastric cancer cells and mesothelial cells may play an active role during diapedesis. In this study we detected the expression of connexin 43 (Cx43) in primary gastric cancer tissues, intra-abdominal exfoliated cancer cells, and matched metastatic peritoneal tissues. We found that the expression of Cx43 in primary gastric cancer tissues was significantly decreased; the intra-abdominal exfoliated cancer cells and matched metastatic peritoneal tissues exhibited increasing expression compared with primary gastric cancer tissues. BGC-823 and SGC-7901 human gastric cancer cells were engineered to express Cx43 or Cx43T154A (a mutant protein that only couples gap junctions but provides no intercellular communication) and were co-cultured with human peritoneal mesothelial cells (HPMCs). Heterocellular GJIC and diapedesis through HPMC monolayers on matrigel-coated coverslips were investigated. We found that BGC-823 and SGC-7901 gastric cancer cells expressing Cx43 formed functional heterocellular gap junctions with HPMC monolayers within one hour. A significant increase in diapedesis was observed in engineered Cx43-expressing cells compared with Cx43T154A and control group cells, which suggested that the observed upregulation of diapedesis in Cx43-expressing cells required heterocellular GJIC. Further study revealed that the gastric cancer cells transmigrated through the intercellular space between the mesothelial cells via a paracellular route. Our results suggest that the abnormal expression of Cx43 plays an essential role in peritoneal metastasis and that Cx43-mediated heterocellular GJIC between gastric cancer cells and mesothelial cells may be an important regulatory

  16. Gastric cancer incidence and mortality is associated with altitude in the mountainous regions of Pacific Latin America

    PubMed Central

    Torres, Javier; Correa, Pelayo; Ferreccio, Catterina; Hernandez-Suarez, Gustavo; Herrero, Rolando; Cavazza-Porro, Maria; Dominguez, Ricardo; Morgan, Douglas

    2013-01-01

    In Latin America, gastric cancer is a leading cancer, and countries in the region have some of the highest mortality rates worldwide, including Chile, Costa Rica, and Colombia. Geographic variation in mortality rates is observed both between neighboring countries and within nations. We discuss epidemiological observations suggesting an association between altitude and gastric cancer risk in Latin America. In the Americas, the burden of gastric cancer mortality is concentrated in the mountainous areas along the Pacific rim, following the geography of the Andes sierra, from Venezuela to Chile, and the Sierra Madre and Cordillera de Centroamérica, from southern Mexico to Costa Rica. Altitude is probably a surrogate for host genetic, bacterial, dietary, and environmental factors that may cluster in the mountainous regions. For example, H. pylori strains from patients of the Andean Nariño region of Colombia display European ancestral haplotypes, whereas strains from the Pacific coast are predominantly of African origin. The observation of higher gastric cancer rates in the mountainous areas is not universal: the association is absent in Chile, where risk is more strongly associated with the age of H. pylori acquisition and socio-economic determinants. The dramatic global and regional variations in gastric cancer incidence and mortality rates offer the opportunity for scientific discovery and focused prevention programs. PMID:23224271

  17. Gastric cancer incidence and mortality is associated with altitude in the mountainous regions of Pacific Latin America.

    PubMed

    Torres, Javier; Correa, Pelayo; Ferreccio, Catterina; Hernandez-Suarez, Gustavo; Herrero, Rolando; Cavazza-Porro, Maria; Dominguez, Ricardo; Morgan, Douglas

    2013-02-01

    In Latin America, gastric cancer is a leading cancer, and countries in the region have some of the highest mortality rates worldwide, including Chile, Costa Rica, and Colombia. Geographic variation in mortality rates is observed both between neighboring countries and within nations. We discuss epidemiological observations suggesting an association between altitude and gastric cancer risk in Latin America. In the Americas, the burden of gastric cancer mortality is concentrated in the mountainous areas along the Pacific rim, following the geography of the Andes sierra, from Venezuela to Chile, and the Sierra Madre and Cordillera de Centroamérica, from southern Mexico to Costa Rica. Altitude is probably a surrogate for host genetic, bacterial, dietary, and environmental factors that may cluster in the mountainous regions. For example, H. pylori strains from patients of the Andean Nariño region of Colombia display European ancestral haplotypes, whereas strains from the Pacific coast are predominantly of African origin. The observation of higher gastric cancer rates in the mountainous areas is not universal: the association is absent in Chile, where risk is more strongly associated with the age of H. pylori acquisition and socio-economic determinants. The dramatic global and regional variations in gastric cancer incidence and mortality rates offer the opportunity for scientific discovery and focused prevention programs.

  18. AKT plays a crucial role in gastric cancer

    PubMed Central

    SASAKI, TAKAMITSU; YAMASHITA, YUICHI; KUNIYASU, HIROKI

    2015-01-01

    The AKT protein is involved in the phosphatidylinositol-3 kinase signaling pathway and is a vital regulator of survival, proliferation and differentiation in various types of cells. Helicobacter pylori infection induces epithelial cell proliferation and oxidative stress in chronic gastritis. These alterations lead to telomere shortening, resulting in the activation of telomerase. AKT, in particular, is activated by H. pylori-induced inflammation. AKT then promotes the expression of human telomerase reverse transcriptase, which encodes a catalytic subunit of telomerase, and induces telomerase activity, an essential component of the process of carcinogenesis. AKT activation is increased in gastric mucosa with carcinogenic properties and is associated with the low survival of patients with gastric cancer. The findings of the present study suggest that AKT is pivotal in gastric carcinogenesis and progression. PMID:26622541

  19. Early gastric cancer in Menetrier’s disease

    PubMed Central

    Remes-Troche, Jose Maria; Zapata-Colindres, Juan Carlos; Starkman, Ivethe; De Anda, Jazmin; Arista-Nasr, Julian; Valdovinos-Diaz, Miguel Angel

    2009-01-01

    Uncommon conditions such as pernicious anaemia and hypertrophic gastropathies have been considered as risk factors for gastric cancer; however, the exact increase in risk is unknown. Menetrier’s disease is a rare hyperproliferative disorder of the stomach caused by an overexpression of tumour growth factor α, a ligand for the tyrokinase epidermal growth factor receptor, resulting in a selective expansion of surface mucous cells in the body and fundus of the stomach. There have been nearly 200 cases of Menetrier’s disease reported in the literature yet less than 15 have been associated with gastric adenocarcinoma. Here, we report an early stage gastric adenocarcinoma detected incidentally in a patient recently diagnosed with Menetrier’s disease. PMID:21686802

  20. Prediction of the 10-year probability of gastric cancer occurrence in the Japanese population: the JPHC study cohort II.

    PubMed

    Charvat, Hadrien; Sasazuki, Shizuka; Inoue, Manami; Iwasaki, Motoki; Sawada, Norie; Shimazu, Taichi; Yamaji, Taiki; Tsugane, Shoichiro

    2016-01-15

    Gastric cancer is a particularly important issue in Japan, where incidence rates are among the highest observed. In this work, we provide a risk prediction model allowing the estimation of the 10-year cumulative probability of gastric cancer occurrence. The study population consisted of 19,028 individuals from the Japanese Public Health Center cohort II who were followed-up from 1993 to 2009. A parametric survival model was used to assess the impact on the probability of gastric cancer of clinical and lifestyle-related risk factors in combination with serum anti-Helicobacter pylori antibody titres and pepsinogen I and pepsinogen II levels. Based on the resulting model, cumulative probability estimates were calculated and a simple risk scoring system was developed. A total of 412 cases of gastric cancer occurred during 270,854 person-years of follow-up. The final model included (besides the biological markers) age, gender, smoking status, family history of gastric cancer and consumption of highly salted food. The developed prediction model showed good predictive performance in terms of discrimination (optimism-corrected c-index: 0.768) and calibration (Nam and d'Agostino's χ(2) test: 14.78; p values = 0.06). Estimates of the 10-year probability of gastric cancer occurrence ranged from 0.04% (0.02, 0.1) to 14.87% (8.96, 24.14) for men and from 0.03% (0.02, 0.07) to 4.91% (2.71, 8.81) for women. In conclusion, we developed a risk prediction model for gastric cancer that combines clinical and biological markers. It might prompt individuals to modify their lifestyle habits, attend regular check-up visits or participate in screening programmes.

  1. Gastric cancer risk and erythrocyte composition of docosahexaenoic acid with anti-inflammatory effects.

    PubMed

    Kuriki, Kiyonori; Wakai, Kenji; Matsuo, Keitaro; Hiraki, Akio; Suzuki, Takeshi; Yamamura, Yoshitaka; Yamao, Kenji; Nakamura, Tsuneya; Tatematsu, Masae; Tajima, Kazuo

    2007-11-01

    Infection with Helicobacter pylori is linked to inflammation and is the main cause of peptic ulcer, gastritis, and gastric malignancies. To examine associations between gastric cancer risk and the erythrocyte composition of docosahexaenoic acid (DHA), a fatty acid with anti-inflammatory and apoptosis-inducing effects, here we conducted a case-control study of 179 incident gastric cancer cases and 357 noncancer controls (matched by age, sex, and season of sample collection). Dietary information and blood samples were collected from all subjects, and erythrocyte fatty acid levels were measured using accelerated solvent extraction and gas-liquid chromatography. Gastric cancer risk did not seem to be directly associated with dietary intake of fish and n-3 highly unsaturated fatty acids (HUFAs), such as DHA, derived from fish. However, risk was inversely associated with erythrocyte compositions of n-3 HUFAs [the highest to the lowest tertile, odds ratio (OR), 0.39; 95% confidence interval (95% CI), 0.23-0.68; P(trend)<0.005] and DHA (OR, 0.47; 95% CI, 0.28-0.79; P(trend)<0.01). Particularly strong associations were noted for well-differentiated type lesions and n-3 HUFAs (OR, 0.10; 95% CI, 0.03-0.35; P(trend)=0.0005) as well as DHA (OR, 0.20; 95% CI, 0.07-0.58; P(trend)<0.01) values. In conclusion, the erythrocyte composition of DHA was found to be negatively linked to risk of gastric cancer, especially of well-differentiated adenocarcinoma. Further studies are needed to investigate mechanisms of action of DHA relevant to antitumor effects in the stomach.

  2. ANGPTL2 expression in gastric cancer tissues and cells and its biological behavior

    PubMed Central

    Sheng, Wei-Zhong; Chen, Yu-Sheng; Tu, Chuan-Tao; He, Juan; Zhang, Bo; Gao, Wei-Dong

    2016-01-01

    AIM To explore expression of angiopoietin-like protein 2 (ANGPTL2) and its effect on biological behavior such as proliferation and invasiveness in gastric cancer. METHODS Western blotting was used to detect expression of ANGPTL2 in 60 human normal gastric tissues, 60 human gastric cancer tissues and gastric cell lines including GES-1, N87, SGC7901, BGC823 and PAMC82. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and Transwell assay were used to detect the proliferation and invasive ability of gastric cancer cells. RESULTS Compared to normal tissues, ANGPTL2 protein levels were significantly upregulated in gastric tissues, and this level was closely correlated with gastric tumor grade, clinical stage and lymph node metastasis. Compared to GES-1 cells, ANGPTL2 mRNA and protein levels were significantly increased in gastric cancer cells including N87, SGC7901, BGC823 and PAMC82. The expression of ANGPTL2 in highly malignant gastric cancer cell lines BGC823 and PAMC82 was significantly higher than in low malignancy gastric cancer cell lines N87 and SGC7901. MTT and Transwell experiments indicated that the proliferation rate and invasive ability of stable overexpressed gastric cancer cells was faster than in cells transfected with Lv-NC and blank control cells, and the invasive ability of stable overexpressed gastric cancer cells was higher than that of cells transfected with Lv-NC and blank control cells. CONCLUSION ANGPTL2 contributed to proliferation and invasion of gastric cancer cells. In clinical treatment, ANGPTL2 may become a new target for treatment of gastric cancer. PMID:28058016

  3. 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

  4. Decreased Sp1 Expression Mediates Downregulation of SHIP2 in Gastric Cancer Cells

    PubMed Central

    Ye, Yan; Qian, Xue Yi; Xiao, Miao Miao; Shao, Yu Ling; Guo, Li Mei; Liao, Dong Ping; Da, Jie; Zhang, Lin Jie; Xu, Jiegou

    2017-01-01

    Past studies have shown that the Src homology 2-containing inositol 5-phosphatase 2 (SHIP2) is commonly downregulated in gastric cancer, which contributes to elevated activation of PI3K/Akt signaling, proliferation and tumorigenesis of gastric cancer cells. However, the mechanisms underlying the reduced expression of SHIP2 in gastric cancer remain unclear. While gene copy number variation analysis and exon sequencing indicated the absence of genomic alterations of SHIP2, bisulfite genomic sequencing (BGS) showed promoter hypomethylation of SHIP2 in gastric cancer cells. Analysis of transcriptional activity of SHIP2 promoter revealed Specificity protein 1 (Sp1) was responsible for the regulation of SHIP2 expression in gastric cancer cells. Furthermore, Sp1 expression, but not Sp3, was frequently downregulated in gastric cancer compared with normal gastric mucosa, which was associated with a paralleled reduction in SHIP2 levels in gastric cancer. Moreover, overexpression of Sp1 inhibited cell proliferation, induced apoptosis, suppressed cell motility and invasion in gastric cancer cells in vitro, which was, at least in part, due to transcriptional activation of SHIP2 mediated by Sp1, thereby inactivating Akt. Collectively, these results indicate that decreased expression of transcription factor Sp1 contributes to suppression of SHIP2 in gastric cancer cells. PMID:28117748

  5. A mutational signature in gastric cancer suggests therapeutic strategies

    DOE PAGES

    Alexandrov, Ludmil B.; Nik-Zainal, Serena; Siu, Hoi Cheong; ...

    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

  6. 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.

  7. 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

  8. 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

  9. 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

  10. HOTTIP and HOXA13 are oncogenes associated with gastric cancer progression.

    PubMed

    Chang, Shuai; Liu, Junsong; Guo, Shaochun; He, Shicai; Qiu, Guanglin; Lu, Jing; Wang, Jin; Fan, Lin; Zhao, Wei; Che, Xiangming

    2016-06-01

    A long non-coding RNA named HOTTIP (HOXA transcript at the distal tip) coordinates the activation of various 5' HOXA genes which encode master regulators of development through targeting the WDR5/MLL complex. HOTTIP acts as an oncogene in several types of cancers, whereas its biological function in gastric cancer has never been studied. In the present study, we investigated the role of HOTTIP in gastric cancer. We found that HOTTIP was upregulated in gastric cancer cell lines. Knockdown of HOTTIP in gastric cancer cells inhibited cell proliferation, migration and invasion. Moreover, downregulation of HOTTIP led to decreased expression of homeobox protein Hox-A13 (HOXA13) in gastric cancer cell lines. HOXA13 was involved in HOTTIP‑induced malignant phenotypes of gastric cancer cells. Our data showed that the levels of HOTTIP and HOXA13 were both markedly upregulated in gastric cancer tissues compared with their counterparts in non-tumorous tissues. Furthermore, the expression levels of HOTTIP and HOXA13 were both higher in gastric cancer which was poorly differentiated, at advanced TNM stages and exhibited lymph node-metastasis. Spearman analyses indicated that HOTTIP and HOXA13 had a highly positive correlation both in non-tumor mucosae and cancer lesions. Collectively, these findings suggest that HOTTIP and HOXA13 play important roles in gastric cancer progression and provide a new insight into therapeutic treatment for the disease.

  11. TCF7L2 rs7903146 polymorphism is associated with gastric cancer: A case-control study in the Venezuelan population

    PubMed Central

    Torres, Keila; Labrador, Luis; Valderrama, Elvis; Chiurillo, Miguel Angel

    2016-01-01

    AIM: To explore the association between TCF7L2 rs12255372 and rs7903146 single nucleotide polymorphisms (SNPs) and gastric cancer risk in Venezuelan patients. METHODS: We performed a case-control study including 122 paraffin-embedded archived intestinal-type gastric cancer samples and 129 biopsies obtained by superior endoscopy from chronic gastritis patients. Gastric cancer samples were classified according the degree of carcinoma differentiation. Genomic DNA was extracted from tissues, and the two SNPs of TCF7L2 gene (rs12255372 and rs7903146) were genotyped by polymerase chain reaction-restriction fragment length polymorphism reactions. Multiple regression analysis with adjustments for age and gender were performed and best-fitting models of inheritance were determined. Statistic powers were post-hoc calculated. RESULTS: After adjusting for age and sex the TCF7L2 rs7903146 TT genotype was associated with gastric cancer risk under the recessive genetic model (OR = 3.11, 95%CI: 1.22-7.92, P = 0.017). We further investigated the distribution of rs12255372 and rs7903146 genotypes according gastric cancer stratified by degree of differentiation, and we observed that carriers of rs7903146 T allele (CT + TT vs CC) had a significantly increased risk of moderate/well differentiated gastric cancer (dominant model, OR = 2.55, 95%CI: 1.35-4.80, P = 0.004), whereas the rs7903146 TT genotype was associated with poorly differentiated gastric cancer in the recessive model (OR = 3.65, 95%CI: 1.25-10.62, P = 0.018). We did not find association between rs12255372 SNP and the susceptibility of developing gastric cancer. CONCLUSION: TCF7L2 rs7903146 polymorphism is associated with gastric cancer risk in the Venezuelan population, and could be related to determine the degree of differentiation of tumor cells. PMID:27605886

  12. [Gastric cancer in the Honorio Delgado Regional Hospital in Arequipa].

    PubMed

    Estremadoyro, O; Alvarez de Trillo, Y; Estremadoyro Stagnaro, L; Gamero Tejada, D

    1995-01-01

    We present the study of 120 cases of gastric carcinoma, observed in the Hospital Regional Honorio Delgado from Arequipa Peru, in 2683 gastroscopies, with 4.5% of incidence. We offer date of age, sex, race, occupation, antecedents, social-economic conditions, clinics, diagnosis, pathologies aspects and mortality.

  13. Thyroid autoantibodies and thyroid function in patients with gastric cancer.

    PubMed

    Syrigos, K N; Konstantoulakis, M M; Constantoulakis, M; Marafelia, P; Koutras, D; Golematis, B C

    1994-01-01

    Antibodies against thyroid antigens are commonly found in patients with chronic gastritis type B (20-30%) and pernicious anaemia (50%), two disorders that predispose to gastric cancer. In addition, thyroid disease in increased incidence has been reported in breast and in colon cancer. In order to determine a) the incidence of antithyroid antibodies (ATA) in gastric cancer, b) the thyroid function in patients with ATA and c) the correlation between ATA and the presence of chronic gastritis, we examined the sera of 32 patients with gastric cancer (GC) for the presence of antithyroglobulin and antimicrosomal antibodies. T3, T4 and TSH values were also measured. The sera of 36 patients with malignant tumours of the GI tract other than stomach (OMT) and of 40 healthy blood donors were used as controls. Three of the 32 GC patients had antithyroglobulin antibodies, 4 had antimicrosomal and one had both types. Of the eight patients with ATA (25%) only two had hypothyroidism and another two histologically diagnosed chronic gastritis. Three sera of the healthy controls and one of the OMT had also antithyroid antibodies. To conclude, a significant number of patients with GC had ATA as compared to controls (p < 0.01) but the presence of ATA did not necessarily indicate an abnormality of thyroid function. The presence of antibodies did not correlate with chronic gastritis type B.

  14. [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.

  15. Risks of Stomach (Gastric) Cancer Screening

    MedlinePlus

    ... in which malignant (cancer) cells form in the lining of the stomach. The stomach is a J- ... outermost) layer. Stomach cancer begins in the cells lining the mucosal layer and spreads through the outer ...

  16. Could Adjuvant Chemotherapy after Surgery Benefit Elderly Patients with Advanced Gastric Cancer?

    PubMed Central

    Jeong, Jin Woon; Kwon, In Gyu; Son, Young-Gil

    2016-01-01

    Purpose The aim of this study was to evaluate tolerance to adjuvant chemotherapy, and to compare survival between treatments using only surgery and using surgery with adjuvant chemotherapy, in elderly patients with advanced gastric cancer who were ≥75 years of age. Materials and Methods Patients ≥75 years of age who were diagnosed with pathological stage II or III gastric cancer were identified retrospectively and categorized into the surgery only and surgery with adjuvant chemotherapy groups. Clinicopathological and survival data were compared between these two groups. Results Among the 130 patients studied, 67 patients underwent curative surgery only, and 63 patients received adjuvant chemotherapy after curative surgery. In the latter group, adverse events were reported in 24 patients (38.1%). The treatments were discontinued in 19 patients (30.2%) owing to any reason. The overall 5-year survival rates of the surgery only and the surgery with adjuvant chemotherapy groups did not differ significantly (44.1% vs. 30.7%, respectively; P=0.804). Among 90 death events, deaths from recurrences of gastric cancer occurred in 42 patients. Multivariate analyses revealed that the American Society of Anesthesiologists score and the depths of tumor invasions were related to survival, and the addition of adjuvant chemotherapy after surgery did not influence survival. Conclusions The decision for the addition of adjuvant chemotherapy for elderly patients should be taken after considering the condition of individual patients and their life expectancies. PMID:28053813

  17. Natural History of Early Gastric Cancer: a Case Report and Literature Review.

    PubMed

    Iwai, Tomohiro; Yoshida, Masao; Ono, Hiroyuki; Kakushima, Naomi; Takizawa, Kohei; Tanaka, Masaki; Kawata, Noboru; Ito, Sayo; Imai, Kenichiro; Hotta, Kinichi; Ishiwatari, Hirotoshi; Matsubayashi, Hiroyuki

    2017-03-01

    Early detection and treatment decrease the mortality rate associated with gastric cancer (GC). However, the natural history of GC remains unclear. An 85-year-old woman was referred to our hospital for evaluation of a gastric tumor. Esophagogastroduodenoscopy identified a 6 mm, flat-elevated lesion at the lesser curvature of the antrum. A biopsy specimen showed a well-differentiated tubular adenocarcinoma. The depth of the lesion was estimated to be intramucosal. Although the lesion met the indications for endoscopic resection, periodic endoscopic follow-up was performed due to the patient's advanced age and comorbidities. The mucosal GC invaded into the submucosa 3 years later, and finally progressed to advanced cancer 5 years after the initial examination. The patient died of tumor hemorrhage 6.4 years after the initial examination. In this case, mucosal GC progressed to advanced GC, eventually leading to the patient's death from GC. Early and appropriate treatment is required to prevent GC-related death.

  18. Gastric microbiota features associated with cancer risk factors and clinical outcomes: A pilot study in gastric cardia cancer patients from Shanxi, China.

    PubMed

    Yu, Guoqin; Hu, Nan; Wang, Lemin; Wang, Chaoyu; Han, Xiao-You; Humphry, Mike; Ravel, Jacques; Abnet, Christian C; Taylor, Philip R; Goldstein, Alisa M

    2017-03-20

    Little is known about the link between gastric microbiota and the epidemiology of gastric cancer. In order to determine the epidemiologic and clinical relevance of gastric microbiota, we used 16 S ribosomal RNA gene sequencing analysis to characterize the composition and structure of the gastric microbial community of 80 paired samples (non-malignant and matched tumor tissues) from gastric cardia adenocarcinoma (GCA) patients in Shanxi, China. We also used PICRUSt to predict microbial functional profiles. Compared to patients without family history of upper gastrointestinal (UGI) cancer in the non-malignant gastric tissue microbiota, patients with family history of UGI cancer had higher Helicobacter pylori (Hp) relative abundance (median: 0.83 vs. 0.38, p = 0.01) and lower alpha diversity (median observed species: 51 vs. 85, p = 0.01). Patients with higher (vs. lower) tumor grade had higher Hp relative abundance (0.73 vs. 0.18, p = 0.03), lower alpha diversity (observed species, 66 vs. 89, p = 0.01), altered beta diversity (weighted UniFrac, p = 0.002) and significant alterations in relative abundance of five KEGG functional modules in non-malignant gastric tissue microbiota. Patients without metastases had higher relative abundance of Lactobacillales than patients with metastases (0.05 vs. 0.01, p = 0.04) in non-malignant gastric tissue microbiota. These associations were observed in non-malignant tissues but not in tumor tissues. In conclusion, this study showed a link of gastric microbiota to a major gastric cancer risk factor and clinical features in GCA patients from Shanxi, China. Studies with both healthy controls and gastric cardia and noncardia cancer cases across different populations are needed to further examine the association between gastric cancer and the microbiota.

  19. 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

  20. Application of Artificial Neural Network in Predicting the Survival Rate of Gastric Cancer Patients

    PubMed Central

    Biglarian, A; Hajizadeh, E; Kazemnejad, A; Zali, MR

    2011-01-01

    Background: The aim of this study was to predict the survival rate of Iranian gastric cancer patients using the Cox proportional hazard and artificial neural network models as well as comparing the ability of these approaches in predicting the survival of these patients. Methods: In this historical cohort study, the data gathered from 436 registered gastric cancer patients who have had surgery between 2002 and 2007 at the Taleghani Hospital (a referral center for gastrointestinal cancers), Tehran, Iran, to predict the survival time using Cox proportional hazard and artificial neural network techniques. Results: The estimated one-year, two-year, three-year, four-year and five-year survival rates of the patients were 77.9%, 53.1%, 40.8%, 32.0%, and 17.4%, respectively. The Cox regression analysis revealed that the age at diagnosis, high-risk behaviors, extent of wall penetration, distant metastasis and tumor stage were significantly associated with the survival rate of the patients. The true prediction of neural network was 83.1%, and for Cox regression model, 75.0%. Conclusion: The present study shows that neural network model is a more powerful statistical tool in predicting the survival rate of the gastric cancer patients compared to Cox proportional hazard regression model. Therefore, this model recommended for the predicting the survival rate of these patients. PMID:23113076

  1. Epidemiology of gastric cancer in the gangetic areas of west bengal.

    PubMed

    Saha, Ashis Kumar; Maitra, Somnath; Hazra, Subhas Chandra

    2013-01-01

    There is marked geographical variation in the distribution and incidence of stomach cancer. We tried here to describe the pattern of relationships of age, sex, religion distribution, symptom profile, histological subtypes and Helicobacter pylori (H. pylori) infection with gastric cancer in Gangetic West Bengal. This study was done over a period of five years (2006-2010). The patients residing in the Gangetic areas of West Bengal presenting with upper gastrointestinal symptoms underwent UGI endoscopy. Among gastric cancer patients, demographic characteristics, symptomatology, macroscopic and histologic lesions and H. pylori status were analyzed. At confidence level 95%, "Z" and "P" value were calculated to find significance. Among 23851 patients underwent UGI endoscopy, 14106 were males, 9745 females, 17889 Hindus and 5962 Muslims. Among 462 gastric cancer patients, Male : Female 2.7 : 1, Hindus : Muslim 3 : 1, abdominal pain, indigestion, and weight-loss were commonest presentations. Antrum was the commonest site whereas ulceroproliferative type was commonest type. H. pylori positivity was 80.89% in adenocarcinoma with statistically significant relation with intestinal type. In future, our target will be to modify risk factors; it will need further demographic studies and analysis, so that we can detect it earliest.

  2. ITIH3 Is a Potential Biomarker for Early Detection of Gastric Cancer

    PubMed Central

    Chong, Poh Kuan; Lee, Huiyin; Zhou, Jianbiao; Liu, Shaw-Cheng; Shia Loh, Marie Chiew; Wang, Ting Ting; Chan, Siew Pang; Smoot, Duane T.; Ashktorab, Hassan; Yan So, Jimmy Bok; Lim, Khong Hee; Yeoh, Khay Guan; Lim, Yoon Pin

    2013-01-01

    Gastric cancer has one of the highest morbidities and mortalities worldwide. Early detection is key measure to improve the outcome of gastric cancer patients. In our efforts to identify potential markers for gastric cancer detection, we coupled xenotransplantation mouse model with a plasma proteomic approach. MKN45 gastric cancer cells were subcutaneously injected into nude mice and plasma samples from mice bearing different sizes of tumors were collected and subjected to iTRAQ and mass spectrometry analysis. ITIH3 protein was found to be more highly expressed in plasma of tumor bearing mice compared to control. Subsequent screening of ITIH3 expression in 167 clinical plasma samples, including 83 cancer-free subjects and 84 gastric cancer patients, revealed higher ITIH3 level in the plasma of gastric cancer patients. A receiver operating characteristics (ROC) curve estimated a maximal sensitivity of 96% at 66% specificity for ITIH3 in gastric cancer detection. In addition, plasma from early stage gastric cancer patient has significantly (p < 0.001) higher level of ITIH3 compared to that from noncancer subject. Our data suggest that ITIH3 may be a useful biomarker for early detection of gastric cancer. PMID:20515073

  3. Increased Serum Pepsinogen II Level as a Marker of Pangastritis and Corpus-Predominant Gastritis in Gastric Cancer Prevention.

    PubMed

    Massarrat, Sadegh; Haj-Sheykholeslami, Arghavan

    2016-02-01

    Serum pepsinogen I and II are considered as indicators of changes in gastric morphology. Important publications from the last decades are reviewed with regard to the serum level of these biomarkers for the diagnosis of normal gastric mucosa, diffuse gastritis and its change to atrophic gastritis and intestinal metaplasia as well as gastric cancer. Due to the low sensitivity of serum biomarkers for diagnosis of gastric cancer, especially at its early stage and the poor prognosis of the tumor at the time of diagnosis, its prevention by eradication of H. pylori remains the mandatory strategy. On the other hand, the severity of regression and non-reversibility of precancerous lesions and intestinal metaplasia in gastric mucosa through eradication of H. pylori make it necessary to diagnose diffuse gastritis at its early stage. Increased serum pepsinogen II compared to normal serum pepsinogen I seems to indicate the presence of diffuse gastritis without precancerous lesions suitable for eradication of H. pylori infection, when it is serologically positive. A diagram illustrates the strategy of this therapeutic measure depending on the age of people and the level of serum biomarkers in areas with high gastric cancer prevalence.

  4. 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

  5. A Case of Gastric Cancer with Situs Inversus Totalis

    PubMed Central

    Suh, Byoung Jo

    2017-01-01

    Situs inversus totalis (SIT) is a rare congenital anomaly that refers to a completely reversed location of the abdominal and thoracic organs. We report the case of 50-year-old man with gastric cancer and SIT who was diagnosed during a screening esophagogastroduodenoscopy. A chest X-ray, abdominopelvic computed tomography, and 18F-fluoro2-deoxyglucose-D-glucose-positron emission tomography scans revealed SIT. We performed a radical subtotal gastrectomy with D2 lymph node dissection. Advanced surgical skill is required to perform a precise lymphadenectomy in a patient with SIT by visualizing the exact mirror image of the anatomy during the operation. The patient had an uneventful intra- and postoperative course and was followed up at the outpatient department without any evidence of recurrence. In conclusion, surgery in a patient with gastric cancer and SIT can be safely performed by paying attention to the inverted anatomic structures during the operation. PMID:28203176

  6. 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

  7. Targeted treatment of liver metastasis from gastric cancer using specific binding peptide

    PubMed Central

    Gong, Jianfeng; Tan, Gewen; Sheng, Nengquan; You, Weiqiang; Wang, Zhigang

    2016-01-01

    Gastric cancer ranks the first in China among all gastrointestinal cancers in terms of incidence, and liver metastasis is the leading cause of death for patients with advanced gastric cancer. Tumor necrosis factor (TNF) is a cytokine commonly chosen as the target for gene therapy against cancers. The specific binding peptide pd20 of gastric cancer cells with a high potential for liver metastasis was fused with human TNF to obtain the pd20-TNF gene using DNA recombinant technique. The expression of the fusion protein was induced and the protein was purified. In vitro activity test showed that the fusion protein greatly improved the membrane permeability of liver cells in nude mice with liver metastasis from gastric cancer. The tumor implantation experiment in nude mice showed that the fusion protein effectively mitigated the cancer lesions. The results provide important clues for developing the drugs for targeted treatment of liver metastasis from gastric cancer. PMID:27347305

  8. Possible association between gastric cancer and bracken fern in Venezuela: an epidemiologic study.

    PubMed

    Alonso-Amelot, M E; Avendaño, M

    2001-01-15

    To explore a possible connection between specific environmental factors that might explain the high rates of stomach cancer in people living in the highlands of western Venezuela, an epidemiologic study was conducted in 2 regions of contrasting topography. The regions embrace 3 Andean states, Mérida, Táchira and Trujillo, and the vicinal lowland surrounding the Maracaibo lake basin of Zulia State. Statistical sanitary records from 1986 to 1996 comprising 5.5 million people in the study area indicated that age-sex-adjusted gastric cancer death rate per 100,000 people (DR) was up to 3.64 times higher in highland than lowland areas, although total cancer-related DRs were comparable in both regions. DRs of other less frequent cancers from the upper alimentary tract [esophagous (1.18/0.99) and mouth-throat (1.39/2.64)] showed comparable values in both regions as well as colorectal, breast, and uterus-cervix cancers, suggesting that the stomach cancer DRs were related to geographically determined factors. Comparison of some nutrition issues, incidence of Helicobacter pylori infection in selected areas, the discovery of the bracken carcinogen ptaquiloside in milk from bracken-fed cows, the prevalence of this plant in mountain cattle households and pasturelands and the rates of bracken-evoked bovine enzootic hematuria led us to conclude that consumption of ptaquiloside-contaminated milk may contribute to human gastric cancer in the Andean states of Venezuela.

  9. 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

  10. 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.

  11. Capecitabine with radiation is an effective adjuvant therapy in gastric cancers

    PubMed Central

    Tham, Chee Kian; Choo, Su Pin; Poon, Donald Yew Hee; Toh, Han Chong; Ong, Simon Yew Kuang; Tan, Sze Huey; Wang, Michael Lian Chek; Foo, Kian Fong

    2010-01-01

    AIM: To analyze the outcome of patients who received concurrent capecitabine (Xeloda) and radiation (XRT) compared to the established concurrent 5-fluorouracil (5-FU) with radiation (5FU-RT) and fluoropyrimidine-based chemotherapy alone as adjuvant treatment in gastric cancers. METHODS: All patients with gastric cancers who received adjuvant treatment at the National Cancer Centre Singapore between 1996 and 2006 were reviewed. Treatment outcomes of patients who received XRT were compared with those who had 5FU-RT or chemotherapy alone as adjuvant therapy for gastric cancers. RESULTS: A total of 108 patients were reviewed. Median age at diagnosis was 60. The majority of the patients (64.8%) had advanced stage III and IV disease (with no distant metastasis). All except 4 patients had D2 gastrectomy. Twenty one patients (19.4%) had positive surgical resection margins. Thirty three patients received XRT compared with 52 who had 5FU-RT and 23 who received chemotherapy alone. For the patients in the chemotherapy-only group, all had fluoropyrimidine-based therapy, with added cisplatin in 7 patients and epirubicin in 2 patients. Median recurrence-free survival was longer for the XRT group (52 mo) compared to the 5FU-RT (35 mo) and chemotherapy-only groups (25 mo) (P = 0.48). The patients in the XRT group achieved similar median overall survival (53 mo) as the 5FU-RT (54 mo) and the chemotherapy-only groups (44 mo) (P = 0.5). CONCLUSION: Capecitabine with concurrent radiation was as effective as concurrent 5FU with radiation or fluoropyrimidine-based chemotherapy alone when used as adjuvant treatment in patients with gastric cancers. PMID:20677345

  12. The role of palliative radiation therapy in symptomatic locally advanced gastric cancer

    SciTech Connect

    Tey, Jeremy . E-mail: Jeremy_Tey@mail.nhg.com.sg; Back, Michael F.; Shakespeare, Thomas P.; Mukherjee, Rahul K.; Lu, Jiade J.; Lee, Khai Mun; Wong, Lea Choung; Leong, Cheng Nang; Zhu Ming

    2007-02-01

    Purpose: To review the outcome of palliative radiotherapy (RT) alone in patients with symptomatic locally advanced or recurrent gastric cancer. Methods and Materials: Patients with symptomatic locally advanced or recurrent gastric cancer who were managed palliatively with RT at Cancer Institute, Singapore were retrospectively reviewed. Study end points included symptom response, median survival, and treatment toxicity (retrospectively scored using the Common Toxicity Criteria v3.0 [CTC]). Results: Between November 1999 and December 2004, 33 patients with locally advanced or recurrent gastric cancer were managed with palliative intent using RT alone. Median age was 76 years (range, 38-90 years). Twenty-one (64%) patients had known distant metastatic disease at time of treatment. Key index symptoms were bleeding (24 patients), obstruction (8 patients), and pain (8 patients). The majority of patients received 30 Gy/10 fractions (17 patients). Dose fractionation regimen ranged from an 8-Gy single fraction to 40 Gy in 16 fractions. Median survival was 145 days, actuarial 12-month survival 8%. A total of 54.3% of patients (13/24) with bleeding responded (median duration of response of 140 days), 25% of patients (2/8) with obstruction responded (median duration of response of 102 days), and 25% of patients (2/8) with pain responded (median duration of response of 105 days). No obvious dose-response was evident. One Grade 3 CTC equivalent toxicity was recorded. Conclusion: External beam RT alone is an effective and well tolerated modality in the local palliation of gastric cancer, with palliation lasting the majority of patients' lives.

  13. Effectiveness of interventions to increase screening for gastric and colorectal cancer in Korea.

    PubMed

    Hong, Nam Soo; Kam, Sin

    2014-01-01

    Public health centers in Korea play an important role at the community level in encouraging residents to participate in cancer screening, usually by sending reminders in the mail and by making phone calls. However, there have not been any studies on the effectiveness of these interventions by public health centers in Korea. The purpose of this study was to evaluate this question. The study was limited to male subjects aged 50-59 years living in one district of Daegu, Korea. A total of 923 subjects were selected for the study among the target population for gastric and colorectal cancer screening as part of the National Cancer Screening Program in 2012. The subjects were randomly assigned to one of four groups: control, postal intervention, telephone intervention, and telephone and postal intervention. Three months after the interventions, the results were confirmed by the National Health Insurance Corporation. Logistic regression analyses were performed to find differences in participation rates in cancer screening for each group. Men who received telephone and postal intervention were most likely (40.5%) to undergo gastric cancer screening, in comparison to the men who received telephone intervention only (31.7%), postal intervention only (22.2%) and those in the control group (17.9%). Also, men who received telephone and postal intervention were most likely (27.8%) to participate in colorectal cancer screening, followed by the men who received telephone intervention only (24.3%), postal intervention only (16.5%), and men in the control group (13.5%). Combined telephone and postal intervention and telephone only intervention as well produced significantly increased rates of participation in cancer screening in comparison to the control group. There was no significant difference, however, between the postal intervention only and control groups for either colorectal or gastric cancer screening.

  14. Expression of Tim-3 in gastric cancer tissue and its relationship with prognosis.

    PubMed

    Cheng, Gui; Li, Min; Wu, Jun; Ji, Mei; Fang, Cheng; Shi, Hongbing; Zhu, Danxia; Chen, Lujun; Zhao, Jiemin; Shi, Liangrong; Xu, Bin; Zheng, Xiao; Wu, Changping; Jiang, Jingting

    2015-01-01

    As a negative regulatory molecule, T-cell immunoglobulin-and mucin domain-3 (Tim-3) plays a crucial role in the tumor immunological tolerance. In the present study, we aimed to determine the Tim-3 expression in gastric cancer tissue and its relationship with clinicopathological parameters and prognosis. The Tim-3 expression was assessed in 52 gastric cancer specimens and 15 gastritis tissues by flow cytometry, and gastritis tissues served as the control. As a result, we found that the Tim-3 expressions on CD4(+)T cells and CD8(+)T cells in gastric cancer tissue was significantly higher than those in gastritis tissue (P=0.022, P=0.047, respectively). The median expression level of Tim-3 on CD4(+)T cells were significantly correlated with clinicopathological parameters, such as tumor size, lymph node metastasis, the depth of tumor invasion and TNM staging (P=0.042, P=0.026, P=0.001, P=0.003, respectively), while it was not correlated with sex, age and histological subtype (all P>0.05). In CD8(+)T cells, the Tim-3 expression was relevant to tumor invasion and TNM staging (P=0.035, P=0.017, respectively), while it was irrelevant to other clinicopathological parameters (all P>0.05). Additionally, Kaplan-Meier survival curves showed that the median overall survival time of patients with lower Tim-3 expression was greater than that of patients with higher Tim-3 expression in CD4(+)T cells and CD8(+)T cells (χ(2)=18.036, P<0.001 and χ(2)=18.036, P<0.001, respectively). Moreover, the multivariate analysis revealed that the Tim-3 expression and TNM stage were independent prognostic factors for gastric cancer patients (P=0.029, P=0.043 and P=0.003, respectively). These results suggest that Tim-3 played an important role in the development and progression of gastric cancer, and it could be used as an independent prognostic factor for gastric cancer patients.

  15. Tumor markers in colorectal cancer, gastric cancer and gastrointestinal stromal cancers: European group on tumor markers 2014 guidelines update.

    PubMed

    Duffy, M J; Lamerz, R; Haglund, C; Nicolini, A; Kalousová, M; Holubec, L; Sturgeon, C

    2014-06-01

    Biomarkers currently play an important role in the detection and management of patients with several different types of gastrointestinal cancer, especially colorectal, gastric, gastro-oesophageal junction (GOJ) adenocarcinomas and gastrointestinal stromal tumors (GISTs). The aim of this article is to provide updated and evidence-based guidelines for the use of biomarkers in the different gastrointestinal malignancies. Recommended biomarkers for colorectal cancer include an immunochemical-based fecal occult blood test in screening asymptomatic subjects ≥50 years of age for neoplasia, serial CEA levels in postoperative surveillance of stage II and III patients who may be candidates for surgical resection or systemic therapy in the event of distant metastasis occurring, K-RAS mutation status for identifying patients with advanced disease likely to benefit from anti-EGFR therapeutic antibodies and microsatellite instability testing as a first-line screen for subjects with Lynch syndrome. In advanced gastric or GOJ cancers, measurement of HER2 is recommended in selecting patients for treatment with trastuzumab. For patients with suspected GIST, determination of KIT protein should be used as a diagnostic aid, while KIT mutational analysis may be used for treatment planning in patients with diagnosed GISTs.

  16. 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.

  17. Cell Senescence: Aging and Cancer

    ScienceCinema

    Campisi, Judith

    2016-07-12

    Scientists have identified a molecular cause behind the ravages of old age and in doing so have also shown how a natural process for fighting cancer in younger persons can actually promote cancer in older individuals.

  18. Ecological study for refrigerator use, salt, vegetable, and fruit intakes, and gastric cancer.

    PubMed

    Park, Boyoung; Shin, Aesun; Park, Sue K; Ko, Kwang-Pil; Ma, Seung Hyun; Lee, Eun-Ha; Gwack, Jin; Jung, En-Joo; Cho, Lisa Y; Yang, Jae Jeong; Yoo, Keun-Young

    2011-11-01

    We used an ecological approach to determine the correlation between vegetable, fruit and salt intakes, refrigerator use, and gastric cancer mortality in Korean population. Information on fruit and vegetable intakes per capita from the National Health and Nutrition Survey, death certificate data from the National Statistical office, refrigerator per household data from Korean Statistical Information Service, and salt/sodium intake data from a cross-sectional survey were utilized. Correlation coefficients were calculated between vegetable and fruit intakes, refrigerator per household, and gastric cancer mortality and between salt and sodium intakes, and gastric cancer mortality and incidence in the four areas. With 5, 10, and 15 years lag time, refrigerator usage and fruit intake were negatively associated with gastric cancer mortality (p < 0.01), but vegetable intake was not associated with gastric cancer mortality. When estimates of salt/sodium intake evaluated by 24-h urine collection in four areas of Korea were compared to the gastric cancer mortality and incidence in these regions, positive correlation was shown between salt/sodium intake, and gastric cancer incidence and mortality. Negative associations between refrigerator use, fruit intake, and gastric cancer mortality and positive associations between salt/sodium intake and gastric cancer mortality and incidence were suggested.

  19. Germline E-cadherin mutations in hereditary diffuse gastric cancer: assessment of 42 new families and review of genetic screening criteria

    PubMed Central

    Brooks-Wilson, A; Kaurah, P; Suriano, G; Leach, S; Senz, J; Grehan, N; Butterfield, Y; Jeyes, J; Schinas, J; Bacani, J; Kelsey, M; Ferreira, P; MacGillivray, B; MacLeod, P; Micek, M; Ford, J; Foulkes, W; Australie, K; Greenberg, C; LaPointe, M; Gilpin, C; Nikkel, S; Gilchrist, D; Hughes, R; Jackson, C; Monaghan, K; Oliveira, M; Seruca, R; Gallinger, S; Caldas, C; Huntsman, D

    2004-01-01

    Background: Mutations in the E-cadherin (CDH1) gene are a well documented cause of hereditary diffuse gastric cancer (HDGC). Development of evidence based guidelines for CDH1 screening for HDGC have been complicated by its rarity, variable penetrance, and lack of founder mutations. Methods: Forty three new gastric cancer (GC) families were ascertained from multiple sources. In 42 of these families at least one gastric cancer was pathologically confirmed to be a diffuse gastric cancer (DGC); the other family had intestinal type gastric cancers. Screening of the entire coding region of the CDH1 gene and all intron/exon boundaries was performed by bi-directional sequencing. Results: Novel mutations were found in 13 of the 42 DGC families (31% overall). Twelve of these mutations occur among the 25 families with multiple cases of gastric cancer and with pathologic confirmation of diffuse gastric cancer phenotype in at least one individual under the age of 50 years. The mutations found include small insertions and deletions, splice site mutations, and three non-conservative amino acid substitutions (A298T, W409R, and R732Q). All three missense mutations conferred loss of E-cadherin function in in vitro assays. Multiple cases of breast cancers including pathologically confirmed lobular breast cancers were observed both in mutation positive and negative families. Conclusion: Germline truncating CDH1 mutations are found in 48% of families with multiple cases of gastric cancer and at least one documented case of DGC in an individual under 50 years of age. We recommend that these criteria be used for selecting families for CDH1 mutational analysis. PMID:15235021

  20. 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.

  1. 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.

  2. Hereditary diffuse gastric cancer: surgery, surveillance and unanswered questions.

    PubMed

    Cisco, Robin M; Norton, Jeffrey A

    2008-08-01

    Hereditary diffuse gastric cancer (HDGC) is an inherited cancer-susceptibility syndrome characterized by autosomal dominance and high penetrance. In 30-50% of cases, a causative germline mutation in CDH1, the E-cadherin gene, may be identified. Female carriers of CDH1 mutations also have an increased (20-40%) risk of lobular breast cancer. Endoscopic surveillance of patients with CDH1 mutations is ineffective because early foci of HDGC are typically small and underlie normal mucosa. CDH1 mutation carriers are therefore offered the option of prophylactic gastrectomy, which commonly reveals early foci of invasive signet-ring cell cancer. We review recommendations for genetic testing, surveillance and prophylactic surgery in HDGC. Areas for future research are discussed, including development of new screening modalities, optimal timing of prophylactic gastrectomy, identification of additional causative mutations in HDGC, management of patients with CDH1 missense mutations and prevention/early detection of lobular breast cancer in CDH1 mutation carriers.

  3. Waterpipe Tobacco Smoking and Gastric Cancer Risk among Vietnamese Men

    PubMed Central

    Lai, Hang Thi Minh; Koriyama, Chihaya; Tokudome, Shinkan; Tran, Hoc Hieu; Tran, Long Thanh; Nandakumar, Athira; Akiba, Suminori; Le, Ngoan Tran

    2016-01-01

    Background The association of waterpipe tobacco (WPT) smoking with gastric cancer (GC) risk was suggested. Methods A hospital-based case-control study was conducted to examine the association of WPT with GC risk among Vietnamese men, in Hanoi city, during the period of 2003–2011. Newly-diagnosed GC cases (n = 454) and control patients (n = 628) were matched by age (+/- 5 years) and the year of hospitalization. Information on smoking and alcohol drinking habits and diet including salty food intake and fruits/vegetables consumption were obtained by the interview. Maximum likelihood estimates of odds ratios (ORs) and corresponding 95% confidence intervals (Cis) were obtained using conditional logistic regression models. Results The group with the highest consumption of citrus fruits showed a significantly low GC risk (OR = 0.6, 95%CI = 0.4–0.8, P for trend = 0.002). However, there was no association of raw vegetable consumption with GC risk. Referring to never smokers, GC risk was significantly higher in current WPT smokers (OR = 1.8, 95%CI = 1.3–2.4), and it was more evident in exclusively WPT smokers (OR = 2.7, 95%CI = 1.2–6.5). GC risk tended to be higher with daily frequency and longer duration of WPT smoking but these trends were not statistically significant (P for trend: 0.144 and 0.154, respectively). GC risk of those who started smoking WPT before the age of 25 was also significantly high (OR = 3.7, 95%CI = 1.2–11.3). Neither cigarette smoking nor alcohol drinking was related to GC risk. Conclusion The present findings revealed that WPT smoking was positively associated with GC risk in Vietnamese men. PMID:27802311

  4. Exosomes derived from gastric cancer cells activate NF-κB pathway in macrophages to promote cancer progression.

    PubMed

    Wu, Lijun; Zhang, Xu; Zhang, Bin; Shi, Hui; Yuan, Xiao; Sun, Yaoxiang; Pan, Zhaoji; Qian, Hui; Xu, Wenrong

    2016-09-01

    Exosomes are nano-sized membrane vesicles secreted by both normal and cancer cells. Emerging evidence indicates that cancer cells derived exosomes contribute to cancer progression through the modulation of tumor microenvironment. However, the effects of exosomes derived from gastric cancer cells on macrophages are not well understood. In this study, we investigated the biological role of gastric cancer cells derived exosomes in the activation of macrophages. We demonstrated that gastric cancer cells derived exosomes activated macrophages to express increased levels of proinflammatory factors, which in turn promoted tumor cell proliferation and migration. In addition, gastric cancer cells derived exosomes remarkably upregulated the phosphorylation of NF-κB in macrophages. Inhibiting the activation of NF-κB reversed the upregulation of proinflammatory factors in macrophages and blocked their promoting effects on gastric cancer cells. Moreover, we found that gastric cancer cells derived exosomes could also activate macrophages from human peripheral blood monocytes through the activation of NF-κB. In conclusion, our results suggest that gastric cancer cells derived exosomes stimulate the activation of NF-κB pathway in macrophages to promote cancer progression, which provides a potential therapeutic approach for gastric cancer by interfering with the interaction between exosomes and macrophages in tumor microenvironment.

  5. 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

  6. Gastric cancer burden of last 40 years in North China (Hebei Province)

    PubMed Central

    Liang, Di; Liang, Suoyuan; Jin, Jing; Li, Daojuan; Shi, Jin; He, Yutong

    2017-01-01

    Abstract Gastric cancer (GC) is the second leading cause of cancer death in China. It is well known that Cixian in Hebei Province is one of the highest risk areas of GC in China and worldwide. This study aims to accurate assessment of GC burden and trend in high-risk area (Hebei Province) from 1973 to 2013. The authors analyzed GC data from 21 population-based cancer registries which represented 15.25% of the entire population of Hebei Province. The collected data were stratified by 5-year age groups, gender, and area. Mortality of GC was extracted from national death surveys from 1973 to 1975, 1990 to 1992, 2004 to 2005, and 2011 to 2013. Trend analysis (1988–2013) in a high-risk area (Cixian) used the Joinpoint Model. The age–period–cohort model was used to estimate the effects of age, period, and birth cohort in GC incidence in Cixian from 1988 to 2013. The crude incidence of GC in 2011 to 2013 was 40.37/100,000 (57.53/100,000 in males and 22.55/100,000 in females). The corresponding age-standardized rate by world age-standard population was 32.18/100,000 (48.87/100,000 in males and 17.53/100,000 in females), which was 2.66-fold (2.81-fold in male and 2.34-fold in female) higher than that in the world (12.1/100,000, 17.4/100,000 in males and 7.5/100,000 in females). Males in rural areas had the highest incidence, with an age-standardized rate of 70.51/100,000. Gastric cardia cancer was primary anatomical subsite which accounting for 59.59% in GC, followed by gastric corpus (13.92%), gastric antrum (11.43%), gastric fundus (4.99%), and overlapping lesion of gastric (4.17%). The age-standardized rate of mortality from GC displayed a significant downward trend (P = 0.019) in Hebei Province from the 1990s (31.44/100,000) to the 2010s (24.63/100,000). In Cixian, the incidence of GC rose from 1988 (38.25/100,000) to 2009 (65.11/100,000). Cixian, where population-based screening of upper gastrointestinal cancer was performed, experienced the increasing rate

  7. The Korean Gastric Cancer Cohort Study: Study Protocol and Brief Results of a Large-Scale Prospective Cohort Study

    PubMed Central

    Eom, Bang Wool; Kim, Young-Woo; Nam, Byung-Ho; Ryu, Keun Won; Jeong, Hyun-Yong; Park, Young-Kyu; Lee, Young-Joon; Yang, Han-Kwang; Yu, Wansik; Yook, Jeong-Hwan; Song, Geun Am; Youn, Sei-Jin; Kim, Heung Up; Noh, Sung-Hoon; Park, Sung Bae; Yang, Doo-Hyun; Kim, Sung

    2016-01-01

    Purpose This study aimed to establish a large-scale database of patients with gastric cancer to facilitate the development of a national-cancer management system and a comprehensive cancer control policy. Materials and Methods An observational prospective cohort study on gastric cancer was initiated in 2010. A total of 14 cancer centers throughout the country and 152 researchers were involved in this study. Patient enrollment began in January 2011, and data regarding clinicopathological characteristics, life style-related factors, quality of life, as well as diet diaries were collected. Results In total, 4,963 patients were enrolled until December 2014, and approximately 5% of all Korean patients with gastric cancer annually were included. The mean age was 58.2±11.5 years, and 68.2% were men. The number of patients in each stage was as follows: 3,394 patients (68.4%) were in stage IA/B; 514 patients (10.4%), in stage IIA/B; 469 patients (9.5%), in stage IIIA/B/C; and 127 patients (2.6%), in stage IV. Surgical treatment was performed in 3,958 patients (79.8%), endoscopic resection was performed in 700 patients (14.1%), and 167 patients (3.4%) received palliative chemotherapy. The response rate for the questionnaire on the quality of life was 95%; however, diet diaries were only collected for 27% of patients. Conclusions To provide comprehensive information on gastric cancer for patients, physicians, and government officials, a large-scale database of Korean patients with gastric cancer was established. Based on the findings of this cohort study, an effective cancer management system and national cancer control policy could be developed. PMID:27752396

  8. Janus Kinase 2 Polymorphisms Are Associated with Risk in Patients with Gastric Cancer in a Chinese Population

    PubMed Central

    Guo, Renhua; Zhang, Zhihong; Xu, Hao; Yang, Chao; Zhu, Yi

    2013-01-01

    Aim To evaluate the impact of the Janus kinase 2 single nucleotide polymorphisms (SNPs) on gastric cancer risk. Methods In this hospital-based, case–control study, the genotypes were identified by polymerase chain reaction–restriction fragment length polymorphism protocols in 661 individuals (359 gastric cancer patients and 302 age and sex matched cancer-free controls). Results Both the frequency of A allele in rs2230724 and G allele in rs1887427 were more frequent in patients with gastric cancer (P = 0.013 and 0.001, respectively). Compared with the common genotype, subjects with the (AG+AA) genotypes of rs2230724 and the (AG+GG) genotypes of rs1887427 had a 59% and 98% increased risk of developing gastric cancer, respectively (P = 0.010, adjusted OR = 1.59, 95% CI = 1.12–2.27; P<0.001, adjusted OR = 1.98, 95% CI = 1.39–2.81, respectively). Further stratified analysis showed that the association between the risk of gastric cancer and the rare genotypes of rs2230724 were more profound in the subgroups of elder individuals (>56 years), males, nonsmokers and urban subjects, while the association between the risk and the rare genotypes of rs1887427 persisted in subgroups of younger individuals (≤56 years), males, nonsmokers and both of rural and urban subjects. Conclusion The JAK2 gene rs2230724 and rs1887427 polymorphisms are associated with an increased risk of gastric cancer in a Chinese Han population. PMID:23717640

  9. Localized amyloidosis of the stomach mimicking a superficial gastric cancer.

    PubMed

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

    2016-06-01

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

  10. 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.

  11. The direct effect of estrogen on cell viability and apoptosis in human gastric cancer cells.

    PubMed

    Qin, Jian; Liu, Min; Ding, Qianshan; Ji, Xiang; Hao, Yarong; Wu, Xiaomin; Xiong, Jie

    2014-10-01

    Epidemiology researches indicated that gastric cancer is a male-predominant disease; both expression level of estrogen and expression pattern of estrogen receptors (ERs) influence its carcinogenesis. But the direct effect of estrogen on gastric cancer cells is still unclear. This study aimed to explore the direct effect of β-estradiol (E2) on gastric cancer cells. SGC7901 and BGC823 were treated with a serial of concentrations of E2. The survival rates of both the cell lines were significantly reduced, and the reduction of viability was due to apoptosis triggered by E2 treatment. Caspase 3 was activated in response to the increasing E2 concentration in both SGC7901 and BGC823. Cleaved Caspase 3 fragments were detected, and the expression levels of Bcl-2 and Bcl-xL were reduced. Apoptosis was further confirmed by flow cytometry. The expression level of PEG10, an androgen receptor target gene, was reduced during E2 treatment. Both ERα and ERβ were expressed in these cell lines, and the result of bioinformatics analysis of gastric cancer from GEO datasets indicated that the expression levels of both ERα and ERβ were significantly higher in noncancerous gastric tissues than in gastric cancer tissues. Our research indicated that estrogen can reduce cell viability and promote apoptosis in gastric cancer cells directly; ERs expression level is associated with gastric cancer. Our research will help to understand the mechanism of gender disparity in gastric cancer.

  12. Evaluation of Outcome and Tolerability of Combination Chemotherapy with Capecitabine and Oxaliplatin as First Line Therapy in Advanced Gastric Cancer.

    PubMed

    Mashhadi, Mohammad Ali; Sepehri, Zahra; Bakhshipour, Ali Reza; Zivari, Ali; Danesh, Hossein Ali; Metanat, Hasan Ali; Karimkoshteh, Azra; Hashemi, Seyed Mehdi; Rahimi, Hossein; Kiani, Zohre

    2016-10-01

    Background: Combination chemotherapy is accepted as a high efficacy treatment for gastric cancer, whereas choice of standard treatment is unclear. Multiple chemotherapeutic regimens have been used to achieve higher efficacy and lower toxicity. This study was designed to evaluate the treatment results of advanced gastric cancer with Capecitabine and Oxaliplatin regimen. Subjects and Methods: All cases with documented gastric adenocarcinoma and advanced disease were candidates for receiving Xelox regimen (Capecitabine - 750 mg/m(2)/twice daily/ 1-14 days and Oxaliplatin 125 mg/m(2) in 1st day). Results: Twenty five cases with advanced gastric cancer entered in study while 24 cases continued treatment protocol and were evaluated. Mean age was 59.5 ± 12.1 years (range: 20-75), male and female cases were 66.7% and 33.3%, respectively. All cases received at least four cycles of Xelox regimen. Overall response rate was 74.99% with 29.16% complete response. Overall survival rate was 13 ± 0.53 months and DFS (disease-free survival) was 6 ± 1.09 months. Extremities neuropathy (62.5%), headache (45.8%) and muscle cramps (29.2%) were the most common complains. Haematological changes were rare and 16.7% of cases had mild cytopenia. Treatment related death was not observed. Conclusion: Xelox regimen is a safe and highly effective first line treatment for gastric cancer; however, considering it as first line therapy needs larger studies.

  13. Evaluation of Outcome and Tolerability of Combination Chemotherapy with Capecitabine and Oxaliplatin as First Line Therapy in Advanced Gastric Cancer

    PubMed Central

    Mashhadi, Mohammad Ali; Sepehri, Zahra; Bakhshipour, Ali Reza; Zivari, Ali; Danesh, Hossein Ali; Metanat, Hasan Ali; Karimkoshteh, Azra; Hashemi, Seyed Mehdi; Rahimi, Hossein; Kiani, Zohre

    2016-01-01

    Background: Combination chemotherapy is accepted as a high efficacy treatment for gastric cancer, whereas choice of standard treatment is unclear. Multiple chemotherapeutic regimens have been used to achieve higher efficacy and lower toxicity. This study was designed to evaluate the treatment results of advanced gastric cancer with Capecitabine and Oxaliplatin regimen. Subjects and Methods : All cases with documented gastric adenocarcinoma and advanced disease were candidates for receiving Xelox regimen (Capecitabine – 750 mg/m2/twice daily/ 1-14 days and Oxaliplatin 125 mg/m2 in 1st day). Results: Twenty five cases with advanced gastric cancer entered in study while 24 cases continued treatment protocol and were evaluated. Mean age was 59.5 ± 12.1 years (range: 20-75), male and female cases were 66.7% and 33.3%, respectively. All cases received at least four cycles of Xelox regimen. Overall response rate was 74.99% with 29.16% complete response. Overall survival rate was 13 ± 0.53 months and DFS (disease-free survival) was 6 ± 1.09 months. Extremities neuropathy (62.5%), headache (45.8%) and muscle cramps (29.2%) were the most common complains. Haematological changes were rare and 16.7% of cases had mild cytopenia. Treatment related death was not observed. Conclusion: Xelox regimen is a safe and highly effective first line treatment for gastric cancer; however, considering it as first line therapy needs larger studies. PMID:27928475

  14. Co-ordinated overexpression of SIRT1 and STAT3 is associated with poor survival outcome in gastric cancer patients.

    PubMed

    Zhang, Shu; Huang, Shuling; Deng, Chao; Cao, Yu; Yang, Jun; Chen, Guangxia; Zhang, Bin; Duan, Chaoqin; Shi, Jiong; Kong, Bo; Friess, Helmut; Zhao, Nanyi; Huang, Chen; Huang, Xiaoli; Wang, Lei; Zou, Xiaoping

    2017-01-03

    In many gastric cancer patients, the disease is diagnosed in an advanced stage and therefore the mortality levels are high. Because there is a need to identify novel early diagnostic and prognostic biomarkers, we tested whether SIRT1 and STAT3 are good candidates. Towards this, we used patient tissues representing different stages of gastric cancer including gastric pre-cancerous lesions, early gastric cancer, and advanced gastric cancer, and probed SIRT1, STAT3 and phosphorylated STAT3 (pSTAT3) levels using immunohistochemistry. Our results revealed upregulated expression of SIRT1 in all stages of gastric cancer compared with noncancerous gastric mucosa, suggesting that high SIRT1 levels are likely involved in establishing gastric neoplasticity. However, STAT3 and pSTAT3 levels remained low until the gastric mucosa reached the tumor stage. Moreover, co-ordinated high expression of SIRT1 and STAT3 predicted poor overall survival for advanced gastric cancer patients. In addition, through analysis of gastric cancer patients from the TCGA dataset, we identified SIRT2 as an independent prognostic factor in gastric cancer patients. We postulate that SIRT1 and STAT3 are potential early diagnostic and prognostic markers of gastric cancer. Our study also shows that SIRT1 acts a gatekeeper during gastric tumorigenesis.

  15. Guanine nucleotide binding protein-like 3 is a potential prognosis indicator of gastric cancer.

    PubMed

    Chen, Jing; Dong, Shuang; Hu, Jiangfeng; Duan, Bensong; Yao, Jian; Zhang, Ruiyun; Zhou, Hongmei; Sheng, Haihui; Gao, Hengjun; Li, Shunlong; Zhang, Xianwen

    2015-01-01

    Guanine nucleotide binding protein-like 3 (GNL3) is a GIP-binding nuclear protein that has been reported to be involved in various biological processes, including cell proliferation, cellular senescence and tumorigenesis. This study aimed to investigate the expression level of GNL3 in gastric cancer and to evaluate the relationship between its expression and clinical variables and overall survival of gastric cancer patients. The expression level of GNL3 was examined in 89 human gastric cancer samples using immunohistochemistry (IHC) staining. GNL3 in gastric cancer tissues was significantly upregulated compared with paracancerous tissues. GNL3 expression in adjacent non-cancerous tissues was associated with sex and tumor size. Survival analyses showed that GNL3 expression in both gastric cancer and adjacent non-cancerous tissues were not related to overall survival. However, in the subgroup of patients with larger tumor size (≥ 6 cm), a close association was found between GNL3 expression in gastric cancer tissues and overall survival. GNL3-positive patients had a shorter survival than GNL3-negative patients. Our study suggests that GNL3 might play an important role in the progression of gastric cancer and serve as a biomarker for poor prognosis in gastric cancer patients.

  16. Quality assurance manual of endoscopic screening for gastric cancer in Japanese communities.

    PubMed

    Hamashima, Chisato; Fukao, Akira

    2016-09-02

    The Japanese government introduced endoscopic screening for gastric cancer in 2015 as a public policy based on the Japanese guidelines on gastric cancer screening. To provide appropriate endoscopic screening for gastric cancer in Japanese communities, we developed a quality assurance manual of endoscopic screening and recommend 10 strategies with their brief descriptions as follows: (i) Formulation of a committee responsible for implementing and managing endoscopic screening, and for deciding the suitable implementation methods in consideration of the local context; (ii) Development of an interpretation system that leads to a final judgement to standardize endoscopic examination and improve its accuracy; (iii) Preparation of management and reporting systems for adverse effects by the committee for safety management; (iv) Obtaining informed consent before operation following adequate explanations regarding the benefits and harms of endoscopic screening; (v) Avoidance of frequent screenings to reduce false-positive results and overdiagnosis. As a reference, the target age group is ≥50 years, and the screening interval is 2 years; (vi) Keeping the biopsy rate within 10% as post-biopsy bleeding may occur. Before endoscopic screening, any history of antithrombotic drug usage should be checked; (vii) Nonadministration of sedation in endoscopic screening for safety management; (viii) Adherence to proper endoscopic cleaning and disinfection to reduce infection; (ix) Use of a checklist to achieve optimal program preparation when municipal governments introduce endoscopic screening; (x) Identification of the aims and roles by referring to a checklist if primary care physicians decide to participate in endoscopic screening.

  17. Conformal radiotherapy in the adjuvant treatment of gastric cancer: Review of 82 cases

    SciTech Connect

    Kassam, Zahra |; Lockwood, Gina |; O'Brien, Catherine; Brierley, James |; Swallow, Carol ||; Oza, Amit |; Siu, Lillian |; Knox, Jennifer J. |; Wong, Rebecca |; Cummings, Bernard; Kim, John |; Moore, Malcolm |; Ringash, Jolie |. E-mail: jolie.ringash@rmp.uhn.on.cag

    2006-07-01

    Background: The Intergroup 0116 study showed a survival benefit with adjuvant chemoradiotherapy (CRT) for resected gastric cancer. We report our experience using conformal radiotherapy (RT). Methods and Materials: Eighty-two patients with resected gastric or gastroesophageal junction (GEJ) adenocarcinoma, Stage IB to IV (M0), were treated with 45 Gy in 25 fractions using a 5-field conformal technique. Chemotherapy was in accordance with the Intergroup 0116 study, or infusional 5-fluorouracil and cisplatin in a phase I/II trial. Results: Mean age was 56.4 years. Median follow-up was 22.8 months. Grade 3 or greater acute toxicity (National Cancer Institute Common Terminology Criteria of Adverse Events, version 3.0) was noted in 57% of patients (upper gastrointestinal tract 34%, hematologic 33%). One patient died of neutropenic sepsis. Radiation Therapy Oncology Group Grade 3 late toxicity included esophageal strictures (3 patients) and small bowel obstruction (1 patient). Full course CRT was completed by 67% of patients. Of 26 patients who relapsed, 20 died. Site of first relapse was available on 23 patients: 8 locoregional and distant, 4 locoregional alone, 11 distant alone. Overall and relapse-free survival were 69% and 54% at 3 years. Conclusion: Adjuvant CRT for gastric cancer, even with conformal RT, is associated with significant toxicity. Survival was comparable to that reported in the Intergroup 0116 study.

  18. Prognostic value of preoperative serum lactate dehydrogenase levels for resectable gastric cancer and prognostic nomograms

    PubMed Central

    Zhou, Yi-Xin; Wang, Feng; Zhang, Dong-Sheng; Wang, Feng-Hua; Li, Yu-Hong; Xu, Rui-Hua

    2016-01-01

    The present study aimed to evaluate the prognostic significance of preoperative serum lactate dehydrogenase (SLDH) levels for resected gastric cancer and construct prognostic nomograms for risk prediction. The study cohort consisted of 619 patients with D2-resected gastric cancer. The relationship of SLDH levels with clinicopathological features and clinical outcomes was evaluated. Prognostic nomograms were created using identified prognosticators to predict 3-year overall survival (OS) and 3-year disease-free survival (DFS), and bootstrap validation was performed. High SLDH levels were correlated with old age but not depth of invasion or lymph node metastasis. When assessed as a continuous variable, high SLDH levels were independently associated with poor OS and DFS. Internal validation of the developed nomograms revealed good predictive accuracy (bootstrap-corrected concordance indices: 0.77 and 0.75, respectively for prediction of OS and DFS). The preoperative SLDH levels, an identified unfavorable prognosticator, were incorporated into nomograms along with other clinicopathological features to refine the prediction of clinical outcomes for patients with D2-resected gastric cancer. PMID:27223065

  19. Spasmolytic polypeptide-expressing metaplasia (SPEM) associated with gastric cancer in Iceland.

    PubMed

    Halldórsdóttir, Anna Margrét; Sigurdardóttrir, Margrét; Jónasson, Jón Gunnlaugur; Oddsdóttir, Margrét; Magnússon, Jónas; Lee, Jeffrey R; Goldenring, James R

    2003-03-01

    Recent studies have described a spasmolytic polypeptide-expressing metaplastic cell lineage (SPEM) in the gastric fundic mucosa associated with both chronic H. pylori infection and gastric adenocarcinoma. We investigated the association of SPEM both with early gastric adenocarcinoma and in biopsies taken from patients prior to diagnosis of cancer. Two cohorts were examined. First, gastric resections from 29 patients with early gastric cancer were examined. Second, biopsies taken from 18 patients prior to the diagnosis of gastric cancer were compared with their respective resection specimens as well as with control biopsies from a cohort of 19 patients diagnosed with gastritis without subsequent development of cancer. The presence of SPEM and intestinal metaplasia (IM) adjacent to and distant from the cancer was compared and spasmolytic polypeptide (SP) immunostaining within dysplastic/cancerous cells was identified. SPEM was present adjacent to cancer in all early cancer cases where the tumor was located in the body or at the body/antrum junction, and was present in the body mucosa distant from the cancer in 76% of cases. Intestinal metaplasia was found adjacent to the tumor in 76% of cases and in body sections in 52% of resections. SP immunostaining was noted within cancer cells in 62% of tumors, and within dysplastic cells in 76% of resections where dysplasia was present. SPEM was present in 82% of the biopsies obtained prior to the diagnosis of cancer, compared with only 37% in the gastritis cohort. IM was present in only 57% of biopsies. In conclusion, SPEM is strongly associated with early gastric cancers and is observed in gastric biopsies prior to the development of cancer. In addition, early gastric cancers demonstrated a high incidence of SP expression. These results suggest that SPEM merits consideration as an important pre-neoplastic gastric lesion.

  20. Risk Factors for Hospital Readmission after Radical Gastrectomy for Gastric Cancer: A Prospective Study

    PubMed Central

    Huang, Dong-Dong; Pang, Wen-Yang; Lou, Neng; Chen, Bi-Cheng; Chen, Xiao-Lei; Yu, Zhen; Shen, Xian

    2015-01-01

    Background Hospital readmission is gathering increasing attention as a measure of health care quality and a potential cost-saving target. The purpose of this prospective study was to determine risk factors for readmission within 30 days of discharge after gastrectomy for patients with gastric cancer. Methods We conducted a prospective study of patients undergoing radical gastrectomy for gastric cancer from October 2013 to November 2014 in our institution. The incidence, cause and risk factors for 30-day readmission were determined. Results A total of 376 patients were included in our analysis without loss in follow-up. The 30-day readmission rate after radical gastrectomy for gastric cancer was 7.2% (27of 376). The most common cause for readmission included gastrointestinal complications and postoperative infections. On the basis of multivariate logistic regression analysis, preoperative nutritional risk screening 2002 score ≥ 3 was an independent risk factor for 30-day readmission. Factors not associated with a higher readmission rate included a history of a major postoperative complication during the index hospitalization, prolonged primary length of hospital stay after surgery, a history of previous abdominal surgery, advanced age, body mass index, pre-existing cardiopulmonary comorbidities, American Society of Anesthesiology grade, type of resection, extent of node dissection and discharge disposition. Conclusions Readmission within 30 days of discharge after radical gastrectomy for gastric cancer is common. Patients with nutritional risk preoperatively are at high risk for 30-day readmission. Preoperative optimization of nutritional status of patients at nutritional risk may effectively decrease readmission rates. PMID:25915547

  1. Prognostic nutritional index is an independent prognostic factor for gastric cancer patients with peritoneal dissemination

    PubMed Central

    Nie, Runcong; Yuan, Shuqiang; Chen, Shi; Chen, Xiaojiang; Chen, Yongming; Zhu, Baoyan; Qiu, Haibo; Zhou, Zhiwei; Peng, Junsheng; Chen, Yingbo

    2016-01-01

    Objective The predictive and prognostic role of prognostic nutritional index (PNI) in gastric cancer patients with peritoneal dissemination remains unclear. This study aims to explore the role of the PNI in predicting outcomes of gastric cancer patients with peritoneal dissemination. Methods A total of 660 patients diagnosed with gastric adenocarcinoma with peritoneal metastasis between January 2000 and April 2014 at Sun Yat-sen University Cancer Center and the Sixth Affiliated Hospital of Sun Yat-sen University were retrospectively analyzed. The clinicopathologic characteristics and clinical outcomes of patients with peritoneal dissemination were analyzed. Results Compared with PNI-high group, PNI-low group was correlated with advanced age (P=0.036), worse performance status (P<0.001), higher frequency of ascites (P<0.001) and higher frequency of multisite distant metastasis (P<0.001). Kaplan-Meier survival curves showed that PNI-high group had a significantly longer median overall survival than PNI-low group (13.13 vs. 9.03 months, P<0.001). Multivariate survival analysis revealed that Borrmann type IV (P=0.014), presence of ascites (P=0.017) and lower PNI (P=0.041) were independent poor prognostic factors, and palliative surgery (P<0.001) and first-line chemotherapy (P<0.001) were good prognostic factors. For patients receiving palliative surgery, the postoperative morbidity rates in the PNI-low group and PNI-high group were 9.1% and 9.9%, respectively (P=0.797). The postoperative mortality rate was not significantly different between PNI-low and PNI-high groups (2.3% vs. 0.9%, P=0.362). Conclusions PNI is a useful and practical tool for evaluating the nutritional status of gastric cancer patients with peritoneal dissemination, and is an independent prognostic factor for these patients. PMID:28174485

  2. [Postoperative adjuvant chemotherapy for gastric cancer after the adjuvant chemotherapy trial of S-1 for gastric cancer in Hiroshima prefecture: results from a questionnaire survey and future challenges].

    PubMed

    Yamaguchi, Kakuhiro; Hirabayashi, Naoki; Ninomiya, Motoki; Shinozaki, Katsunori; Hatanaka, Nobutaka; Matsuda, Hiroyuki; Tanabe, Kazuaki

    2013-12-01

    A questionnaire survey on postoperative adjuvant chemotherapy for gastric cancer was conducted for 76 hospitals affiliated with the Hiroshima Oncology Group of Gastric Cancer in Hiroshima prefecture in January 2011. Responses were obtained from 29 hospitals, including 12 core cancer treatment hospitals, and the following results were obtained. The percentage of patients completing 1 year of oral S-1 was >70%, affecting approximately 75% of the entire hospital cohort. Dose reduction was conducted in approximately 30% of patients because of age, poor PS, and renal insufficiency. The standard S-1 regimen (4 weeks of S-1 treatment followed by 2 weeks of rest)was adopted in almost half of the patients, whereas the rest of the patients received another treatment schedule such as 2 weeks of treatment followed by 1 week of rest. Dose reduction and withdrawal of S-1 due to adverse events were conducted more frequently in hospitals with low completion rates of 1-year S- 1 treatment than those with a high completion rate. S-1 was most commonly discontinued because of subjective adverse events and patient request, although the discontinuation rate according to objective adverse events such as bone marrow depression was not very high. The fact that some hospitals had high completion rates suggested the importance of supplementary tools for patient IC.

  3. Gene Expression Signature Analysis Identifies Vorinostat as a Candidate Therapy for Gastric Cancer

    PubMed Central

    Choi, Woonyoung; Park, Yun-Yong; Kim, KyoungHyun; Kim, Sang-Bae; Lee, Ju-Seog; Mills, Gordon B.; Cho, Jae Yong

    2011-01-01

    Background Gastric cancer continues to be one of the deadliest cancers in the world and therefore identification of new drugs targeting this type of cancer is thus of significant importance. The purpose of this study was to identify and validate a therapeutic agent which might improve the outcomes for gastric cancer patients in the future. Methodology/Principal Findings Using microarray technology, we generated a gene expression profile of human gastric cancer–specific genes from human gastric cancer tissue samples. We used this profile in the Broad Institute's Connectivity Map analysis to identify candidate therapeutic compounds for gastric cancer. We found the histone deacetylase inhibitor vorinostat as the lead compound and thus a potential therapeutic drug for gastric cancer. Vorinostat induced both apoptosis and autophagy in gastric cancer cell lines. Pharmacological and genetic inhibition of autophagy however, increased the therapeutic efficacy of vorinostat, indicating that a combination of vorinostat with autophagy inhibitors may therapeutically be more beneficial. Moreover, gene expression analysis of gastric cancer identified a collection of genes (ITGB5, TYMS, MYB, APOC1, CBX5, PLA2G2A, and KIF20A) whose expression was elevated in gastric tumor tissue and downregulated more than 2-fold by vorinostat treatment in gastric cancer cell lines. In contrast, SCGB2A1, TCN1, CFD, APLP1, and NQO1 manifested a reversed pattern. Conclusions/Significance We showed that analysis of gene expression signature may represent an emerging approach to discover therapeutic agents for gastric cancer, such as vorinostat. The observation of altered gene expression after vorinostat treatment may provide the clue to identify the molecular mechanism of vorinostat and those patients likely to benefit from vorinostat treatment. PMID:21931799

  4. Primo Vascular System: An Endothelial-to-Mesenchymal Potential Transitional Tissue Involved in Gastric Cancer Metastasis.

    PubMed

    Ping, An; Zhendong, Su; Rongmei, Qu; Jingxing, Dai; Wei, Chen; Zhongyin, Zhou; Hesheng, Luo; Soh, Kwang-Sup

    2015-01-01

    Gastric cancer is the fourth commonest cancer in the world and the second leading cause of cancer-related death. Investigation of gastric cancer metastasis is one of the hottest and major focuses in cancer research. Growing evidence manifested that primo vascular system (PVS) is a new kind of circulatory system beyond vascular and lymphatic system. Previous researches revealed that PVS is a specific tissue between endothelium and mesenchyme and is involved in cancer, especially in tumor metastasis and regeneration. In current study, we investigated the role of primo vessels in gastric cancer metastasis and its possible relationship to vascular vessels formation. Our results indicated that primo vessels were involved in gastric cancer metastasis. We observed blood vessel-mediated metastasis, primo vessel-mediated metastasis, and an intermediate state between them. We deduced that primo vessels may be precursors of blood vessels. These results possibly provided a thoroughly new theoretic development in cancer metastasis.

  5. Primo Vascular System: An Endothelial-to-Mesenchymal Potential Transitional Tissue Involved in Gastric Cancer Metastasis

    PubMed Central

    Ping, An; Zhendong, Su; Rongmei, Qu; Jingxing, Dai; Wei, Chen; Zhongyin, Zhou; Hesheng, Luo; Soh, Kwang-Sup

    2015-01-01

    Gastric cancer is the fourth commonest cancer in the world and the second leading cause of cancer-related death. Investigation of gastric cancer metastasis is one of the hottest and major focuses in cancer research. Growing evidence manifested that primo vascular system (PVS) is a new kind of circulatory system beyond vascular and lymphatic system. Previous researches revealed that PVS is a specific tissue between endothelium and mesenchyme and is involved in cancer, especially in tumor metastasis and regeneration. In current study, we investigated the role of primo vessels in gastric cancer metastasis and its possible relationship to vascular vessels formation. Our results indicated that primo vessels were involved in gastric cancer metastasis. We observed blood vessel-mediated metastasis, primo vessel-mediated metastasis, and an intermediate state between them. We deduced that primo vessels may be precursors of blood vessels. These results possibly provided a thoroughly new theoretic development in cancer metastasis. PMID:26379752

  6. Use of Adjuvant 5-Fluorouracil and Radiation Therapy After Gastric Cancer Resection Among the Elderly and Impact on Survival

    SciTech Connect

    Strauss, Joshua; Hershman, Dawn L.; Buono, Donna; McBride, Russell; Clark-Garvey, Sean; Woodhouse, Shermian A.; Abrams, Julian A.

    2010-04-15

    Purpose: In randomized trials patients with resected nonmetastatic gastric cancer who received adjuvant chemotherapy and radiotherapy (chemoRT) had better survival than those who did not. We investigated the effectiveness of adjuvant chemoRT after gastric cancer resection in an elderly general population and its effects by stage. Methods and Materials: We identified individuals in the Surveillance, Epidemiology, and End Results-Medicare database aged 65 years or older with Stage IB through Stage IV (M0) gastric cancer, from 1991 to 2002, who underwent gastric resection, using multivariate modeling to analyze predictors of chemoRT use and survival. Results: Among 1,993 patients who received combined chemoRT or no adjuvant therapy after resection, having a later year of diagnosis, having a more advanced stage, being younger, being white, being married, and having fewer comorbidities were associated with combined treatment. Among 1,476 patients aged less than 85 years who survived more than 4 months, the 313 who received combined treatment had a lower mortality rate (hazard ratio, 0.83; 95% confidence interval, 0.71-0.98) than the 1,163 who received surgery alone. Adjuvant therapy significantly reduced the mortality rate for Stages III and IV (M0), trended toward improved survival for Stage II, and showed no benefit for Stage IB. We observed trends toward improved survival in all age categories except 80 to 85 years. Conclusions: The association of combined adjuvant chemoRT with improved survival in an overall analysis of Stage IB through Stage IV (M0) resected gastric cancer is consistent with clinical trial results and suggests that, in an elderly population, adjuvant chemoradiotherapy is effective. However, our observational data suggest that adjuvant treatment may not be effective for Stage IB cancer, is possibly appropriate for Stage II, and shows significant survival benefits for Stages III and IV (M0) for those aged less than 80 years.

  7. Sonic Hedgehog Pathway Contributes to Gastric Cancer Cell Growth and Proliferation

    PubMed Central

    Wan, Jianhua; Zhou, Ji; Zhao, Hailong; Wang, Mei; Wei, Zhuanqin; Gao, Hongyan

    2014-01-01

    Abstract The Sonic Hedgehog (Shh) signaling pathway is commonly activated in gastrointestinal cancer. However, our understanding of the Shh pathway in gastric cancer remains limited. Here we examined the effects of cyclopamine, a specific inhibitor of the Shh signaling pathway, on cell growth and proliferation in gastric primary cancer cells GAM-016 and the MKN-45 cell line. The results showed that the Shh signaling molecules SHH, PTCH, SMO, GLI1, and GLI2 were intact and activated in both types of cells. Furthermore, we observed that cyclopamine inhibited gastric cancer cell proliferation through cell cycle arrest and apoptosis. An in vivo study using NOD/SCID mouse xenografts demonstrated that cyclopamine significantly prevented tumor growth and development. Our study indicated that Shh signaling pathway could promote gastric cancer cell proliferation and tumor development, and blocking this pathway may be a potential strategy in gastric cancer treatment. PMID:24804165

  8. Emerging Role of miRNAs in the Drug Resistance of Gastric Cancer

    PubMed Central

    Riquelme, Ismael; Letelier, Pablo; Riffo-Campos, Angela L.; Brebi, Priscilla; Roa, Juan Carlos

    2016-01-01

    Gastric cancer is the third leading cause of cancer mortality worldwide. Unfortunately, most gastric cancer cases are diagnosed in an advanced, non-curable stage and with a limited response to chemotherapy. Drug resistance is one of the most important causes of therapy failure in gastric cancer patients. Although the mechanisms of drug resistance have been broadly studied, the regulation of these mechanisms has not been completely understood. Accumulating evidence has recently highlighted the role of microRNAs in the development and maintenance of drug resistance due to their regulatory features in specific genes involved in the chemoresistant phenotype of malignancies, including gastric cancer. This review summarizes the current knowledge about the miRNAs’ characteristics, their regulation of the genes involved in chemoresistance and their potential as targeted therapies for personalized treatment in resistant gastric cancer. PMID:27011182

  9. Emerging Role of miRNAs in the Drug Resistance of Gastric Cancer.

    PubMed

    Riquelme, Ismael; Letelier, Pablo; Riffo-Campos, Angela L; Brebi, Priscilla; Roa, Juan Carlos

    2016-03-22

    Gastric cancer is the third leading cause of cancer mortality worldwide. Unfortunately, most gastric cancer cases are diagnosed in an advanced, non-curable stage and with a limited response to chemotherapy. Drug resistance is one of the most important causes of therapy failure in gastric cancer patients. Although the mechanisms of drug resistance have been broadly studied, the regulation of these mechanisms has not been completely understood. Accumulating evidence has recently highlighted the role of microRNAs in the development and maintenance of drug resistance due to their regulatory features in specific genes involved in the chemoresistant phenotype of malignancies, including gastric cancer. This review summarizes the current knowledge about the miRNAs' characteristics, their regulation of the genes involved in chemoresistance and their potential as targeted therapies for personalized treatment in resistant gastric cancer.

  10. Chromoendoscopy in combination with random biopsies does not improve detection of gastric cancer foci in CDH1 mutation positive patients

    PubMed Central

    Hüneburg, Robert; Marwitz, Tim; van Heteren, Peer; Weismüller, Tobias J.; Trebicka, Jonel; Adam, Ronja; Aretz, Stefan; Perez Bouza, Alberto; Pantelis, Dimitrios; Kalff, Jörg C.; Nattermann, Jacob; Strassburg, Cristian P.

    2016-01-01

    Background and study aims: Hereditary diffuse gastric cancer (HGGC), an autosomal dominant tumor-syndrome, accounts for 1 % to 3 % of gastric cancers worldwide. Presumably 30 % to 40 % of all patients fulfilling the clinical guidelines for HDGC are carriers of a pathogenic mutation in the CDH1 gene. Patients often show multiple foci of signet ring cell carcinoma at early age and are advised to undergo prophylactic total gastrectomy (PTG). Our aim was to improve the endoscopic detection of HDGC by using an enhanced endoscopic protocol. Patient and methods: Patients with a proven CDH1 germline mutation identified in our institute were prospectively included. Patients were advised to undergo PTG and offered a baseline endoscopic examination prior surgery. Examination was performed by using high-resolution white-light endoscopy and pan-gastric chromoendoscopy with indigo carmine as dye combined with targeted and multiple random biopsies assessed by an expert histopathologist. Postoperative histopathology was compared with results from endoscopic biopsies. Results: Between September 2012 and November 2014 8 patients with a proven CDH1 germline mutation were included. We conducted 44 targeted (6.3/patient) and 225 random (32.1/patient) biopsies in 7 patients. We detected 1 gastric cancer by random biopsy (14 %). All other examinations showed no signs of cancer. Histopathology of gastrectomy specimen revealed multiple foci of gastric carcinoma in 6 patients (86 %) with a total number of 27 cancer foci. Conclusions: Examination with targeted and random biopsies combined with chromoendoscopy is not able to detect small foci of gastric cancer in CDH1 mutation carriers. Therefore PTG is advocated in these patients. PMID:27995193

  11. Aberrant silencing of the endocrine peptide gene tachykinin-1 in gastric cancer

    SciTech Connect

    David, Stefan; Kan, Takatsugu; Cheng, Yulan; Agarwal, Rachana; Jin, Zhe; Mori, Yuriko

    2009-01-16

    Tachykinin-1 (TAC1) is the precursor protein for neuroendocrine peptides, including substance P, and is centrally involved in gastric secretion, motility, mucosal immunity, and cell proliferation. Here we report aberrant silencing of TAC1 in gastric cancer (GC) by promoter hypermethylation. TAC1 methylation and mRNA expression in 47 primary GCs and 41 noncancerous gastric mucosae (NLs) were analyzed by utilizing real-time quantitative PCR-based assays. TAC1 methylation was more prevalent in GCs than in NLs: 21 (45%) of 47 GCs versus 6 (15%) of 41 NLs (p < 0.01). Microsatellite instability was also associated with TAC1 methylation in GCs. There was no significant association between TAC1 methylation and age, gender, stage, histological differentiation, or the presence of Helicobacter pylori. TAC1 mRNA was markedly downregulated in GCs relative to NLs. 5-Aza-2'-deoxycytidine-induced demethylation of the TAC1 promoter resulted in TAC1 mRNA upregulation. Further studies are indicated to elucidate the functional involvement of TAC1 in gastric carcinogenesis.

  12. [A case of early gastric cancer completely responding to adjuvant chemotherapy for advanced colon cancer].

    PubMed

    Tanaka, Ryo; Kameyama, Hitoshi; Nakano, Mae; Ichikawa, Hiroshi; Hanyu, Takaaki; Nakano, Masato; Ishikawa, Takashi; Shimada, Yoshifumi; Sakata, Jun; Kobayashi, Takashi; Kosugi, Shinichi; Minagawa, Masahiro; Koyama, Yu; Wakai, Toshifumi

    2014-11-01

    A 70-year-old man was referred to our hospital with ascending colon cancer (cT3N1M0, Stage IIIa), which was found during examinations following a positive fecal occult blood test. The patient was also diagnosed with early gastric cancer (cT1a, N0, M0, Stage IA)during a preoperative gastroscopy examination. A laparoscopically assisted right colectomy and D3 lymphadenectomy was performed for the ascending colon cancer. The postoperative pathological diagnosis was Stage IIIb (pT3N2), he was administered in combination with capecitabine plus oxaliplatin (CapeOX) as adjuvant chemotherapy before the treatment for the colon cancer. After 6 months of adjuvant chemotherapy, we were unable to detect any gastric lesions at the same location using gastroscopy, and so diagnosed a clinical complete response. A follow-up gastroscopy 6 months later showed the same findings. The patient has had no recurrence of gastric cancer for 18 months after the initial operation. He will continue to be followed up closely using gastroscopy. In this case, CapeOX as adjuvant chemotherapy for advanced colon cancer was also effective for early gastric cancer.

  13. Mass Eradication of Helicobacter pylori to Prevent Gastric Cancer: Theoretical and Practical Considerations

    PubMed Central

    Lee, Yi-Chia; Chiang, Tsung-Hsien; Liou, Jyh-Ming; Chen, Hsiu-Hsi; Wu, Ming-Shiang; Graham, David Y

    2016-01-01

    Although the age-adjusted incidence of gastric cancer is declining, the absolute number of new cases of gastric cancer is increasing due to population growth and aging. An effective strategy is needed to prevent this deadly cancer. Among the available strategies, screen-and-treat for Helicobacter pylori infection appears to be the best approach to decrease cancer risk; however, implementation of this strategy on the population level requires a systematic approach. The program also must be integrated into national healthcare priorities to allow the limited resources to be most effectively allocated. Implementation will require adoption of an appropriate screening strategy, an efficient delivery system with a timely referral for a positive test, and standardized treatment regimens based on clinical efficacy, side effects, simplicity, duration, and cost. Within the population, there are subpopulations that vary in risk such that a “one size fits all” approach is unlikely to be ideal. Sensitivity analyses will be required to identify whether the programs can be utilized by heterogeneous populations and will likely require adjustments to accommodate the needs of subpopulations. PMID:26696028

  14. Anti-angiogenic therapies for advanced esophago-gastric cancer

    PubMed Central

    Fontana, Elisa; Sclafani, Francesco; Cunningham, David

    2014-01-01

    Neo-vascularization is a vital process for tumor growth and development which involves the interaction between tumor cells and stromal endothelial cells through several growth factors and membranous receptors which ultimately activate pro-angiogenic intracellular signaling pathways. Inhibition of angiogenesis has become a standard treatment option for several tumor types including colorectal cancer, glioblastoma and ovarian cancer. In gastric cancer, the therapeutic role of anti-angiogenic agents is more controversial. Bevacizumab and ramucirumab, two monoclonal antibodies, which target vascular endothelial growth factor-A and vascular endothelial growth factor receptor-2, respectively, have been demonstrated antitumor activity in patients with tumors of the stomach or esophagogastric junction. However, especially for bevacizumab, this antitumor activity has not consistently translated into a survival advantage over standard treatment in randomized trials. In this article, we provide an overview of the role of angiogenesis in gastric cancer and discuss the results of clinical trials that investigated safety and effectiveness of antiangiogenic therapies in this disease. A review of the literature has been done using PubMed, ClinicalTrials.gov website and the ASCO Annual Meeting Library. PMID:25538401

  15. 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.

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

    PubMed

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

    2016-02-09

    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.

  17. Short-term and long-term risk factors in gastric cancer

    PubMed Central

    Verlato, Giuseppe; Marrelli, Daniele; Accordini, Simone; Bencivenga, Maria; Di Leo, Alberto; Marchet, Alberto; Petrioli, Roberto; Zoppini, Giacomo; Muggeo, Michele; Roviello, Franco; de Manzoni, Giovanni

    2015-01-01

    While in chronic diseases, such as diabetes, mortality rates slowly increases with age, in oncological series mortality usually changes dramatically during the follow-up, often in an unpredictable pattern. For instance, in gastric cancer mortality peaks in the first two years of follow-up and declines thereafter. Also several risk factors, such as TNM stage, largely affect mortality in the first years after surgery, while afterward their effect tends to fade. Temporal trends in mortality were compared between a gastric cancer series and a cohort of type 2 diabetic patients. For this purpose, 937 patients, undergoing curative gastrectomy with D1/D2/D3 lymphadenectomy for gastric cancer in three GIRCG (Gruppo Italiano Ricerca Cancro Gastrico = Italian Research Group for Gastric Cancer) centers, were compared with 7148 type 2 diabetic patients from the Verona Diabetes Study. In the early/advanced gastric cancer series, mortality from recurrence peaked to 200 deaths per 1000 person-years 1 year after gastrectomy and then declined, becoming lower than 40 deaths per 1000 person-years after 5 years and lower than 20 deaths after 8 years. Mortality peak occurred earlier in more advanced T and N tiers. At variance, in the Verona diabetic cohort overall mortality slowly increased during a 10-year follow-up, with ageing of the type 2 diabetic patients. Seasonal oscillations were also recorded, mortality being higher during winter than during summer. Also the most important prognostic factors presented a different temporal pattern in the two diseases: while the prognostic significance of T and N stage markedly decrease over time, differences in survival among patients treated with diet, oral hypoglycemic drugs or insulin were consistent throughout the follow-up. Time variations in prognostic significance of main risk factors, their impact on survival analysis and possible solutions were evaluated in another GIRCG series of 568 patients with advanced gastric cancer, undergoing

  18. Breast cancer metastasizing to the stomach mimicking primary gastric cancer: A case report

    PubMed Central

    Yim, Kwangil; Ro, Sang Mi; Lee, Jieun

    2017-01-01

    Breast cancer with stomach metastasis rare with an incidence of 1% or less among metastatic breast cancer patients. We experienced a case of breast cancer metastasizing to the stomach in 65-year-old female patient. She experienced dyspepsia and poor oral intake before visiting the clinic. Diffuse infiltration with nodular mucosal thickening of the stomach wall was observed, suggesting advanced gastric cancer based on gross endoscopic finding. Spread of poorly cohesive tumor cells in the gastric mucosa observed upon hematoxylin and eosin stain resembled signet ring cell carcinoma, but diffuse positive staining for GATA3 in immunohistochemical stain allowed for a conclusive diagnosis of breast cancer metastasizing to the stomach. Based on the final diagnosis, systemic chemotherapy was administered instead of primary surgical resection. After 2 cycles of docetaxel administration, she showed a partial response based on abdominal computed tomography scan. This case is an unusual presentation of breast cancer metastasizing to the gastrointestinal tract.

  19. 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.

  20. Gastric cancer in pregnancy: is laparoscopic gastrectomy with lymph node dissection feasible and safe?

    PubMed Central

    Alshahrani, Amer Saeed

    2017-01-01

    Gastric cancer with pregnancy is rare and usually presents in late and advanced stage. Standard interventions in diagnosing, staging and treatment of cancer may be harmful for the fetus. The treatment of cancer in pregnancy should not differ significantly from the treatment in nonpregnant women. There have been case reports of open gastrectomy for gastric cancer in pregnancy. We present a case of early gastric cancer in a 37-year-old pregnant woman treated with laparoscopic distal gastrectomy with lymph node dissection with no postoperative complications. Laparoscopic distal gastrectomy with lymph node dissection seems to be feasible and safe in pregnancy for a mother and a fetus. PMID:28090507

  1. Influence of age and gender on association between -765G > C COX-2 genetic polymorphism and gastric adenocarcinoma risk: a case-control study in Iran

    PubMed Central

    Rostami, Masumeh; Aznab, Mozaffar; Abachi, Mina

    2012-01-01

    Aim The purpose of this study was to investigate the possible influence of age and gender on association between -765G > C COX-2 genetic polymorphism and gastric adenocarcinoma risk in Iranian patients. Background The promoter polymorphism of COX-2 gene -765G > C has been described to play an important role in many cancers such as gastric cancer. Patients and methods We carried out single-nucleotide polymorphism analysis in Iranian samples including 91 patients and 91 control normal using PCR- RFLP technique. Results Statistical analysis revealed no significant association between GG, GC and CC genotypes and risk of gastric adenocarcinoma. However differences were considered significant (P=0.043) for female subjects with C carrier genotypes (GC and CC) and gastric adenocarcinoma when compared with male patients (P=0.645) and control groups (P=0.653). Also, there was a statistically significant difference between increasing of age and susceptibility for gastric adenocarcinoma (Odd Ratio=1.125, 95% CI=1.089-1.162). Conclusion These results suggested that Iranian C carrier females can be more susceptible for gastric adenocarcinoma in comparison with control group. Also increasing of age should be considered as a risk factor for this disease. PMID:24834195

  2. miR-532 promoted gastric cancer migration and invasion by targeting NKD1.

    PubMed

    Hu, Shaobo; Zheng, Qichang; Wu, Heshui; Wang, Chunyou; Liu, Tao; Zhou, Wei

    2017-03-26

    Gastric cancer is one of the most common human malignant neoplasms, especially in China, its regulatory mechanism is important to develop new therapy approaches. miRNAs have been demonstrated to regulate gastric cancer progression. We found miR-532 was overexpressed in gastric cancer tissues and cells, Wound healing and transwell assay revealed that its overexpression promoted gastric cancer cell migration and invasion, its knockdown inhibited gastric cancer cell migration and invasion. Wnt/β-catenin antagonist naked cuticle homolog 1 (NKD1) was the target of miR-532, miR-532 inhibited NKD1 expression. TOP/FOP luciferase activity analysis suggested miR-532 also increased Wnt/β-catenin pathway activity. Overexpression miR-532 and NKD1 inhibited gastric cancer cell migration and invasion, consistent with miR-532 knockdown. These findings revealed miR-532 promoted gastric cancer cell migration and invasion through inhibiting NKD1 and activated Wnt/β-catenin pathway. We provide a potential target for gastric cancer therapy.

  3. Polymorphism of the salt sensitivity gene angiotensinogen and gastric cancer risk.

    PubMed

    Shibata, Tomoyuki; Tahara, Tomomitsu; Arisawa, Tomiyasu; Hirata, Ichiro

    2011-01-01

    A high-salt diet is a risk factor for gastric cancers other than those caused by Helicobacter pylori. The angiotensinogen (AGT) M235T polymorphism has been associated with salt sensitivity. The aim of the present study was to clarify the association between the AGT M235T polymorphism and gastric cancer. The AGT M235T polymorphism was genotyped using PCR-RFLP analysis in 206 gastric cancers and 210 control biopsies. A logistic-regression analysis was performed to identify an odds ratio to determine whether a correlation exists between genetic polymorphism and risk in patients with gastric cancer as compared to the control samples. Statistical significance was determined using the Mann Whitney U and Chi-square tests. The genotype distribution was found to be MM=9 (4.4%), MT=57 (27.7%), and TT=140 (67.9%) in samples from patients with gastric cancer and MM=8 (3.8%), MT=60 (28.6%) and TT=142 (67.6%) in the control samples. The odds ratio of gastric cancer of the MM genotype associated with the T carrier was 1.0 (0.4-2.7) (P=0.95). The distribution pattern of AGT M235T polymorphism in the gastric cancer cases and controls was not found to be significantly different in this study. Thus, it can be concluded that other sites of AGT polymorphism or other salt sensitivity genes may be associated with gastric cancer.

  4. Increased susceptibility of aging gastric mucosa to injury: the mechanisms and clinical implications.

    PubMed

    Tarnawski, Andrzej S; Ahluwalia, Amrita; Jones, Michael K

    2014-04-28

    This review updates the current views on aging gastric mucosa and the mechanisms of its increased susceptibility to injury. Experimental and clinical studies indicate that gastric mucosa of aging individuals-"aging gastropathy"-has prominent structural and functional abnormalities vs young gastric mucosa. Some of these abnormalities include a partial atrophy of gastric glands, impaired mucosal defense (reduced bicarbonate and prostaglandin generation, decreased sensory innervation), increased susceptibility to injury by a variety of damaging agents such as ethanol, aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs), impaired healing of injury and reduced therapeutic efficacy of ulcer-healing drugs. Detailed analysis of the above changes indicates that the following events occur in aging gastric mucosa: reduced mucosal blood flow and impaired oxygen delivery cause hypoxia, which leads to activation of the early growth response-1 (egr-1) transcription factor. Activation of egr-1, in turn, upregulates the dual specificity phosphatase, phosphatase and tensin homologue deleted on chromosome ten (PTEN) resulting in activation of pro-apoptotic caspase-3 and caspase-9 and reduced expression of the anti-apoptosis protein, survivin. The imbalance between pro- and anti-apoptosis mediators results in increased apoptosis and increased susceptibility to injury. This paradigm has human relevance since increased expression of PTEN and reduced expression of survivin were demonstrated in gastric mucosa of aging individuals. Other potential mechanisms operating in aging gastric mucosa include reduced telomerase activity, increase in replicative cellular senescence, and reduced expression of vascular endothelial growth factor and importin-α-a nuclear transport protein essential for transport of transcription factors to nucleus. Aging gastropathy is an important and clinically relevant issue because of: (1) an aging world population due to prolonged life span; (2) older

  5. Body iron status and gastric cancer risk in the EURGAST study.

    PubMed

    Fonseca-Nunes, Ana; Agudo, Antonio; Aranda, Núria; Arija, Victoria; Cross, Amanda J; Molina, Esther; Sanchez, Maria Jose; Bueno-de-Mesquita, H B As; Siersema, Peter; Weiderpass, Elisabete; Krogh, Vittorio; Mattiello, Amalia; Tumino, Rosario; Saieva, Calogero; Naccarati, Alessio; Ohlsson, Bodil; Sjöberg, Klas; Boutron-Ruault, Marie-Christine; Cadeau, Claire; Fagherazzi, Guy; Boeing, Heiner; Steffen, Annika; Kühn, Tilman; Katzke, Verena; Tjønneland, Anne; Olsen, Anja; Khaw, Kay-Tee; Wareham, Nick; Key, Tim; Lu, Yunxia; Riboli, Elio; Peeters, Petra H; Gavrila, Diana; Dorronsoro, Miren; Quirós, José Ramón; Barricarte, Aurelio; Jenab, Mazda; Zamora-Ros, Raúl; Freisling, Heinz; Trichopoulou, Antonia; Lagiou, Pagona; Bamia, Christina; Jakszyn, Paula

    2015-12-15

    Although it appears biologically plausible for iron to be associated with gastric carcinogenesis, the evidence is insufficient to lead to any conclusions. To further investigate the relationship between body iron status and gastric cancer risk, we conducted a nested case-control study in the multicentric European Prospective Investigation into Cancer and Nutrition (EPIC) study. The study included 456 primary incident gastric adenocarcinoma cases and 900 matched controls that occurred during an average of 11 years of follow-up. We measured prediagnostic serum iron, ferritin, transferrin and C-reactive protein, and further estimated total iron-binding capacity (TIBC) and transferrin saturation (TS). Odds ratios (ORs) and 95% confidence intervals (CIs) for the risk of gastric cancer by iron metrics were estimated from multivariable conditional logistic regression models. After adjusting for relevant confounders, we observed a statistically significant inverse association between gastric cancer and ferritin and TS indices (ORlog2  = 0.80, 95% CI = 0.72-0.88; OR10%increment  = 0.87, 95% CI = 0.78-0.97, respectively). These associations appear to be restricted to noncardia gastric cancer (ferritin showed a p for heterogeneity = 0.04 and TS had a p for heterogeneity = 0.02), and no differences were found by histological type. TIBC increased risk of overall gastric cancer (OR50 µg/dl  = 1.13, 95% CI = 1.02-1.2) and also with noncardia gastric cancer (p for heterogeneity = 0.04). Additional analysis suggests that time between blood draw and gastric cancer diagnosis could modify these findings. In conclusion, our results showed a decreased risk of gastric cancer related to higher body iron stores as measured by serum iron and ferritin. Further investigation is needed to clarify the role of iron in gastric carcinogenesis.

  6. Histone deacetylase 3 inhibits expression of PUMA in gastric cancer cells.

    PubMed

    Feng, Lifeng; Pan, Min; Sun, Jie; Lu, Haiqi; Shen, Qi; Zhang, Shengjie; Jiang, Tingting; Liu, Liangyi; Jin, Wei; Chen, Yan; Wang, Xian; Jin, Hongchuan

    2013-01-01

    During cancer development, tumor suppressor genes were silenced by promoter methylation or histone deacetylation. Histone deacetylases (HDACs) are important to maintain histone deacetylation. HDAC inhibitors (HDACis) were thus proposed as a new therapeutic approach to cancer. The current study aims to understand the effect and molecular mechanisms of HDACis on gastric cancer cells. Trichostatin A (TSA) significantly inhibited the growth of gastric cancer cells by inducing apoptosis. Gene profiling results showed PUMA (p53 upregulated modulator of apoptosis) as one of 122 genes upregulated in TSA-treated gastric cancer cells. PUMA was downregulated in gastric cancer cell lines and primary gastric carcinoma tissues. Patients with low PUMA expression had significant decreases in overall survival (HR, 2.04; p = 0.047). Ectopic PUMA expression inhibited the growth of gastric cancer cells while PUMA depletion promoted cellular growth. The knockdown of HDAC3 but not other HDACs upregulated PUMA expression. HDAC3 could bind to PUMA promoter, which was abrogated after TSA treatment. In contrast to TSA and SB, HDAC3 siRNA failed to upregulate p53 expression but promoted the interaction of p53 with PUMA promoter. In summary, proapoptotic PUMA was downregulated in gastric cancer and its mRNA expression level is a valuable prognosis factor for gastric cancer. HDAC3 is important to downregulate PUMA expression in gastric cancer and HDACis, like TSA, promoted PUMA expression through stabilizing p53 in addition to HDAC3 inhibition. In combination with chemotherapy, targeting HDAC3 might be a promising strategy to induce apoptosis of gastric cancer cells.

  7. 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.

  8. BET inhibition as a new strategy for the treatment of gastric cancer.

    PubMed

    Montenegro, Raquel C; Clark, Peter G K; Howarth, Alison; Wan, Xiao; Ceroni, Alessandro; Siejka, Paulina; Nunez-Alonso, Graciela A; Monteiro, Octovia; Rogers, Catherine; Gamble, Vicki; Burbano, Rommel; Brennan, Paul E; Tallant, Cynthia; Ebner, Daniel; Fedorov, Oleg; O'Neill, Eric; Knapp, Stefan; Dixon, Darren; Müller, Susanne

    2016-07-12

    Gastric cancer is one of the most common malignancies and a leading cause of cancer death worldwide. The prognosis of stomach cancer is generally poor as this cancer is not very sensitive to commonly used chemotherapies. Epigenetic modifications play a key role in gastric cancer and contribute to the development and progression of this malignancy. In order to explore new treatment options in this target area we have screened a library of epigenetic inhibitors against gastric cancer cell lines and identified inhibitors for the BET family of bromodomains as potent inhibitors of gastric cancer cell proliferations. Here we show that both the pan-BET inhibitor (+)-JQ1 as well as a newly developed specific isoxazole inhibitor, PNZ5, showed potent inhibition of gastric cancer cell growth. Intriguingly, we found differences in the antiproliferative response between gastric cancer cells tested derived from Brazilian patients as compared to those from Asian patients, the latter being largely resistant to BET inhibition. As BET inhibitors are entering clinical trials these findings provide the first starting point for future therapies targeting gastric cancer.

  9. BET inhibition as a new strategy for the treatment of gastric cancer

    PubMed Central

    Montenegro, Raquel C.; Clark, Peter G.K.; Howarth, Alison; Wan, Xiao; Ceroni, Alessandro; Siejka, Paulina; Nunez-Alonso, Graciela A.; Monteiro, Octovia; Rogers, Catherine; Gamble, Vicki; Burbano, Rommel; Brennan, Paul E.; Tallant, Cynthia; Ebner, Daniel; Fedorov, Oleg; O'Neill, Eric; Knapp, Stefan; Dixon, Darren; Müller, Susanne

    2016-01-01

    Gastric cancer is one of the most common malignancies and a leading cause of cancer death worldwide. The prognosis of stomach cancer is generally poor as this cancer is not very sensitive to commonly used chemotherapies. Epigenetic modifications play a key role in gastric cancer and contribute to the development and progression of this malignancy. In order to explore new treatment options in this target area we have screened a library of epigenetic inhibitors against gastric cancer cell lines and identified inhibitors for the BET family of bromodomains as potent inhibitors of gastric cancer cell proliferations. Here we show that both the pan-BET inhibitor (+)-JQ1 as well as a newly developed specific isoxazole inhibitor, PNZ5, showed potent inhibition of gastric cancer cell growth. Intriguingly, we found differences in the antiproliferative response between gastric cancer cells tested derived from Brazilian patients as compared to those from Asian patients, the latter being largely resistant to BET inhibition. As BET inhibitors are entering clinical trials these findings provide the first starting point for future therapies targeting gastric cancer. PMID:27259267

  10. Salt, salted food intake, and risk of gastric cancer: epidemiologic evidence.

    PubMed

    Tsugane, Shoichiro

    2005-01-01

    Because gastric cancer is still the most common cancer, its prevention is one of the most important aspects of Japan's cancer control strategy. Observations among Japanese immigrants in the USA and Brazil based on the geographic differences, the trend in cancer incidence with time, and the change in incidence patterns indicate that gastric cancer is closely associated with dietary factors, such as the intake of salt and salted food. In international and intra-Japanese ecological studies, the average salt excretion level, estimated using randomly selected 24-h urine samples in each population, was closely correlated with gastric cancer mortality. Several case-control and cohort studies, including the author's recent works, have shown that a higher intake of some traditional salt-preserved food and salt per se, which was estimated using a validated food-frequency questionnaire, was associated with a risk of gastric cancer. While salted food intake may increase the risk of Helicobacter pylori infection, it can also act synergistically to promote the development of gastric cancer. Based on substantial evidence about the association between salt and salted food intake and the risk of gastric cancer from ecological, case-control, and cohort studies conducted in Japan and other countries, as well as mechanistic plausibility, dietary modification involving less salt and salted food intake is a practical strategy with which to prevent gastric cancer.

  11. Acidified bile acids enhance tumor progression and telomerase activity of gastric cancer in mice dependent on c-Myc expression.

    PubMed

    Wang, Xiaolong; Sun, Lei; Wang, Xijing; Kang, Huafeng; Ma, Xiaobin; Wang, Meng; Lin, Shuai; Liu, Meng; Dai, Cong; Dai, Zhijun

    2017-03-01

    c-Myc overexpression has been implicated in several malignancies including gastric cancer. Here, we report that acidified bile acids enhance tumor progression and telomerase activity in gastric cancer via c-Myc activation both in vivo and in vitro. c-Myc mRNA and protein levels were assessed in ten primary and five local recurrent gastric cancer samples by quantitative real-time polymerase chain reaction and western blotting analysis. The gastric cancer cell line MGC803 was exposed to bile salts (100 μmol/L glycochenodeoxycholic acid and deoxycholic acid) in an acid medium (pH 5.5) for 10 min daily for 60 weeks to develop an MGC803-resistant cell line. Control MGC803 cells were grown without acids or bile salts for 60 weeks as a control. Cell morphology, proliferation, colony formation and apoptosis of MGC803-resistant cells were analyzed after 60 weeks. To determine the involvement of c-Myc in tumor progression and telomere aging in MGC803-resistant cells, we generated xenografts in nude mice and measured xenograft volume and in vivo telomerase activity. The c-Myc and hTERT protein and mRNA levels were significantly higher in local recurrent gastric cancer samples than in primary gastric cancer samples. MGC803-resistant cells showed a marked phenotypic change under normal growth conditions with more clusters and acini, and exhibited increased cell viability and colony formation and decreased apoptosis in vitro. These phenotypic changes were found to be dependent on c-Myc activation using the c-Myc inhibitor 10058-F4. MGC803-resistant cells also showed a c-Myc-dependent increase in xenograft growth and telomerase activity in vivo. In conclusion, these observations support the hypothesis that acidified bile acids enhance tumor progression and telomerase activity in gastric cancer and that these effects are dependent on c-Myc activity. These findings suggest that acidified bile acids play an important role in the malignant progression of local recurrent

  12. Tobacco chewing and risk of gastric cancer: a case-control study in Yemen.

    PubMed

    Al-Qadasi, F A; Shah, S A; Ghazi, H F

    2017-01-23

    This study aimed to assess the risk factors for gastric cancer in Yemen. A hospital-based case-control study of 70 cases and 140 controls was carried out in Sana'a city between May and October 2014. A structured questionnaire was used to collect information through direct interview. Living in rural areas, tobacco chewing and drinking untreated water were significant risk factors for gastric cancer. Frequent consumption of chicken, cheese, milk, starchy vegetables, cucumber, carrots, leeks, sweet pepper, fruit drinks, legumes and olive oil were associated significantly with decreased risk of gastric cancer. Multiple logistic regression analysis showed that chewing tobacco and frequent consumption of white bread were associated with increased risk of gastric cancer, whereas frequent consumption of chicken, cooked potatoes and fruit drinks had an inverse association. Risk of gastric cancer can be prevented by health education and increasing community awareness.

  13. Noncoding RNAs in gastric cancer: Research progress and prospects

    PubMed Central

    Zhang, Meng; Du, Xiang

    2016-01-01

    Noncoding RNAs (ncRNAs) have attracted much attention in cancer research field. They are involved in cellular development, proliferation, differentiation and apoptosis. The dysregulation of ncRNAs has been reported in tumor initiation, progression, invasion and metastasis in various cancers, including gastric cancer (GC). In the past few years, an accumulating body of evidence has deepened our understanding of ncRNAs, and several emerging ncRNAs have been identified, such as PIWI-interacting RNAs (piRNAs) and circular RNAs (circRNAs). The competing endogenous RNA (ceRNA) networks include mRNAs, microRNAs, long ncRNAs (lncRNAs) and circRNAs, which play critical roles in the tumorigenesis of GC. This review summarizes the recent hotspots of ncRNAs involved in GC pathobiology and their potential applications in GC. Finally, we briefly discuss the advances in the ceRNA network in GC. PMID:27547004

  14. Robotic gastrectomy with transvaginal specimen extraction for female gastric cancer patients

    PubMed Central

    Zhang, Shu; Jiang, Zhi-Wei; Wang, Gang; Feng, Xiao-Bo; Liu, Jiang; Zhao, Jian; Li, Jie-Shou

    2015-01-01

    AIM: To describe the application of complete robotic gastrectomy with transvaginal specimen extraction (TVSE) for gastric cancer patients. METHODS: Between July and November 2014, eight female patients who were diagnosed with gastric adenocarcinoma underwent a TVSE following a full robot-sewn gastrectomy. According to the tumor location, the patients were allocated to two different groups; two patients received robotic total gastrectomy with TVSE and the other six received robotic distal gastrectomy with TVSE. RESULTS: Surgical procedures were successfully performed in all eight cases without conversion. The mean age was 55.3 (range, 42-69) years, and the mean body mass index was 23.2 (range, 21.6-26.0) kg/m2. The mean total operative time and blood loss were 224 (range, 200-298) min and 62.5 (range, 50-150) mL, respectively. The mean postoperative hospital stay was 3.6 (range, 3-5) d. The mean number of lymph nodes resected was 23.6 (range, 17-27). None was readmitted within 30 d of postoperation. During the follow-up, no stricture developed nor was any anastomotic leakage detected. CONCLUSION: It is possible to perform a TVSE following a full robot-sewn gastrectomy with standard D2 lymph node resection for female gastric cancer patients. PMID:26715817

  15. Should peri-gastrectomy gastric acidity be our focus among gastric cancer patients?

    PubMed Central

    Huang, Lei; Xu, A-Man; Li, Tuan-Jie; Han, Wen-Xiu; Xu, Jing

    2014-01-01

    AIM: To investigate the necessity and correctness of acid suppression pre- and post-gastrectomy among gastric carcinoma (GC) patients. METHODS: From June 2011 to April 2013, 99 patients who were diagnosed with GC or adenocarcinoma of the gastroesophageal junction (type II or III) and needed surgical management were enrolled. They all underwent gastrectomy by the same operators [35 undergoing total gastrectomy (TG) plus Roux-en-Y reconstruction, 34 distal gastrectomy (DG) plus Billroth I reconstruction, and 30 proximal gastrectomy (PG) plus gastroesophagostomy]. We collected and analyzed their gastrointestinal juice and tissues from the pre-operational day to the 5th day post-operation, and 6 mo post-surgery. Gastric pH was detected with a precise acidity meter. Gastric juice contents including potassium, sodium and bicarbonate ions, urea nitrogen, direct and indirect bilirubin, and bile acid were detected using Automatic Biochemical Analyzer. Data regarding tumor size, histological type, tumor penetration and tumor-node-metastasis (TNM) stage were obtained from the pathological records. Reflux symptoms pre- and 6 mo post-gastrectomy were evaluated by reflux disease questionnaire (RDQ) and gastroesophageal reflux disease questionnaire (GERD-Q). SPSS 16.0 was applied to analyze the data. RESULTS: Before surgery, gastric pH was higher than the threshold of hypoacidity (4.25 ± 1.45 vs 3.5, P = 0.000), and significantly affected by age, tumor size and differentiation grade, and potassium and bicarbonate ions; advanced malignancies were accompanied with higher pH compared with early ones (4.49 ± 1.31 vs 3.66 ± 1.61, P = 0.008). After operation, gastric pH in all groups was of weak-acidity and significantly higher than that pre-gastrectomy; on days 3-5, comparisons of gastric pH were similar between the 3 groups. Six months later, gastric pH was comparable to that on days 3-5; older patients were accompanied with higher total bilirubin level, indicating more serious

  16. Prognostic value of perioperative leukocyte count in resectable gastric cancer

    PubMed Central

    Chen, Xiao-Feng; Qian, Jing; Pei, Dong; Zhou, Chen; Røe, Oluf Dimitri; Zhu, Fang; He, Shao-Hua; Qian, Ying-Ying; Zhou, Yue; Xu, Jun; Xu, Jin; Li, Xiao; Ping, Guo-Qiang; Liu, Yi-Qian; Wang, Ping; Guo, Ren-Hua; Shu, Yong-Qian

    2016-01-01

    AIM: To investigate the prognostic significance of perioperative leukopenia in patients with resected gastric cancer. METHODS: A total of 614 eligible gastric cancer patients who underwent curative D2 gastrectomy and adjuvant chemotherapy were enrolled in this study. The relationship between pre- and postoperative hematologic parameters and overall survival was assessed statistically, adjusted for known prognostic factors. RESULTS: The mean white blood cell count (WBC) significantly decreased after surgery, and 107/614 (17.4%) patients developed p-leukopenia, which was defined as a preoperative WBC ≥ 4.0 × 109/L and postoperative WBC < 4.0 × 109/L, with an absolute decrease ≥ 0.5 × 109/L. The neutrophil count decreased significantly more than the lymphocyte count. P-leukopenia significantly correlated with poor tumor differentiation and preoperative WBC. A higher preoperative WBC and p-leukopenia were independent negative prognostic factors for survival [hazard ratio (HR) = 1.602, 95% confidence interval (CI): 1.185-2.165; P = 0.002, and HR = 1.478, 95%CI: 1.149-1.902; P = 0.002, respectively] after adjusting for histology, Borrmann type, pTNM stage, vascular or neural invasion, gastrectomy method, resection margins, chemotherapy regimens, and preoperative WBC count. The patients with both higher preoperative WBC and p-leukopenia had a worse prognosis compared to those with lower baseline WBC and no p-leukopenia (27.5 mo vs 57.3 mo, P < 0.001). CONCLUSION: Preoperative leukocytosis alone or in combination with postoperative leukopenia could be independent prognostic factors for survival in patients with resectable gastric cancer. PMID:26973420

  17. Role of Helicobacter pylori in gastric cancer: Updates

    PubMed Central

    Khatoon, Jahanarah; Rai, Ravi Prakash; Prasad, Kashi Nath

    2016-01-01

    Helicobacter pylori (H. pylori) infection is highly prevalent in human, affecting nearly half of the world’s population; however, infection remains asymptomatic in majority of population. During its co-existence with humans, H. pylori has evolved various strategies to maintain a mild gastritis and limit the immune response of host. On the other side, presence of H. pylori is also associated with increased risk for the development of various gastric pathologies including gastric cancer (GC). A complex combination of host genetics, environmental agents, and bacterial virulence factors are considered to determine the susceptibility as well as the severity of outcome in a subset of individuals. GC is one of the most common cancers and considered as the third most common cause of cancer related death worldwide. Many studies had proved H. pylori as an important risk factor in the development of non-cardia GC. Although both H. pylori infection and GC are showing decreasing trends in the developed world, they still remain a major threat to human population in the developing countries. The current review attempts to highlight recent progress in the field of research on H. pylori induced GC and aims to provide brief insight into H. pylori pathogenesis, the role of major virulence factors of H. pylori that modulates the host environment and transform the normal gastric epithelium to neoplastic one. This review also emphasizes on the mechanistic understanding of how colonization and various virulence attributes of H. pylori as well as the host innate and adaptive immune responses modulate the diverse signaling pathways that leads to different disease outcomes including GC. PMID:26909129

  18. Organotypic slice cultures of human gastric and esophagogastric junction cancer.

    PubMed

    Koerfer, Justus; Kallendrusch, Sonja; Merz, Felicitas; Wittekind, Christian; Kubick, Christoph; Kassahun, Woubet T; Schumacher, Guido; Moebius, Christian; Gaßler, Nikolaus; Schopow, Nikolas; Geister, Daniela; Wiechmann, Volker; Weimann, Arved; Eckmann, Christian; Aigner, Achim; Bechmann, Ingo; Lordick, Florian

    2016-07-01

    Gastric and esophagogastric junction cancers are heterogeneous and aggressive tumors with an unpredictable response to cytotoxic treatment. New methods allowing for the analysis of drug resistance are needed. Here, we describe a novel technique by which human tumor specimens can be cultured ex vivo, preserving parts of the natural cancer microenvironment. Using a tissue chopper, fresh surgical tissue samples were cut in 400 μm slices and cultivated in 6-well plates for up to 6 days. The slices were processed for routine histopathology and immunohistochemistry. Cytokeratin stains (CK8, AE1/3) were applied for determining tumor cellularity, Ki-67 for proliferation, and cleaved caspase-3 staining for apoptosis. The slices were analyzed under naive conditions and following 2-4 days in vitro exposure to 5-FU and cisplatin. The slice culture technology allowed for a good preservation of tissue morphology and tumor cell integrity during the culture period. After chemotherapy exposure, a loss of tumor cellularity and an increase in apoptosis were observed. Drug sensitivity of the tumors could be assessed. Organotypic slice cultures of gastric and esophagogastric junction cancers were successfully established. Cytotoxic drug effects could be monitored. They may be used to examine mechanisms of drug resistance in human tissue and may provide a unique and powerful ex vivo platform for the prediction of treatment response.

  19. Photoimmunotherapy of Gastric Cancer Peritoneal Carcinomatosis in a Mouse Model

    PubMed Central

    Sato, Kazuhide; Choyke, Peter L.; Kobayashi, Hisataka

    2014-01-01

    Photoimmunotherapy (PIT) is a new cancer treatment that combines the specificity of antibodies for targeting tumors with the toxicity induced by photosensitizers after exposure to near infrared (NIR) light. We performed PIT in a model of disseminated gastric cancer peritoneal carcinomatosis and monitored efficacy with in vivo GFP fluorescence imaging. In vitro and in vivo experiments were conducted with a HER2-expressing, GFP-expressing, gastric cancer cell line (N87-GFP). A conjugate comprised of a photosensitizer, IR-700, conjugated to trastuzumab (tra-IR700), followed by NIR light was used for PIT. In vitro PIT was evaluated by measuring cytotoxicity with dead staining and a decrease in GFP fluorescence. In vivo PIT was evaluated in a disseminated peritoneal carcinomatosis model and a flank xenograft using tumor volume measurements and GFP fluorescence intensity. In vivo anti-tumor effects of PIT were confirmed by significant reductions in tumor volume (at day 15, p<0.0001 vs. control) and GFP fluorescence intensity (flank model: at day 3, PIT treated vs. control p<0.01 and peritoneal disseminated model: at day 3 PIT treated vs. control, p<0.05). Cytotoxic effects in vitro were shown to be dependent on the light dose and caused necrotic cell rupture leading to GFP release and a decrease in fluorescence intensity in vitro. Thus, loss of GFP fluorescence served as a useful biomarker of cell necrosis after PIT. PMID:25401794

  20. Abnormal expression of paxillin correlates with tumor progression and poor survival in patients with gastric cancer

    PubMed Central

    2013-01-01

    Background Paxillin (PXN) has been found to be aberrantly regulated in various malignancies and involved in tumor growth and invasion. The clinicopathological and prognostic significance of PXN in gastric cancer is still unclear. Methods The expression of PXN was determined in paired gastric cancer tissues and adjacent normal tissues by Western blotting and real-time PCR. Immunohistochemistry was performed to detect the expression of PXN in 239 gastric cancer patients. Statistical analysis was applied to investigate the correlation between PXN expression and clinicopathological characteristics and prognosis in patients. Additionally, the effects of PXN on gastric cancer cell proliferation and migration were also evaluated. Results PXN was up-regulated in gastric cancer tissues and cell lines as compared with adjacent normal tissues and normal gastric epithelial cell line GES-1. Overexpression of PXN was correlated with distant metastasis (P = 0.001) and advanced tumor stage (P = 0.021) in gastric cancer patients. Patients with high PXN expression tended to have poor prognosis compared with patients with low PXN expression (P < 0.001). Multivariate analysis demonstrated that PXN expression was an independent prognostic factor (P = 0.020). Moreover, ectopic expression of PXN promotes cell proliferation and migration in AGS cells whereas knockdown of PXN inhibits cell proliferation and migration in SGC7901 cells. Conclusions PXN plays an important role in tumor progression and may be used as a potential prognostic indicator in gastric cancer. PMID:24180516

  1. MET4 Expression Predicts Poor Prognosis of Gastric Cancers with Helicobacter pylori Infection.

    PubMed

    Sakamoto, Naoko; Tsujimoto, Hironori; Takahata, Risa; Brian, Cao; Ping, Zhao; Ito, Nozomi; Shimazaki, Hideyuki; Ichikura, Takashi; Hase, Kazuo; Vande Woude, George F; Shinomiya, Nariyoshi

    2016-12-23

    Role of HGF/SF-MET signaling is important in cancer progression, but its relation with Helicobacter pylori-positive gastric cancers remains to be elucidated. In total, 201 patients with primary gastric carcinoma who underwent curative or debulking resection without preoperative chemotherapy were studied. MET4 and anti-HGF/SF mAbs were used for immunohistochemical analysis. Survival of gastric cancer patients was estimated by Kaplan-Meier method and compared with log-rank. Cox proportional hazards models were fit to determine the independent association of MET-staining status with outcome. The effect of live H. pylori bacteria on cell signaling and biological behaviors was evaluated using gastric cancer cell lines. MET4-positive gastric cancers showed poorer prognosis than MET4-negative cases (overall survival, P = 0.02; relapse-free survival, P = 0.06). Positive staining for MET4 was also a statistically significant factor to predict poor prognosis in H. pylori-positive cases (overall survival, P < 0.01; relapse-free survival, P = 0.01) but not in H. pylori-negative cases. Gastric cancers positively stained with both HGF/SF and MET4 showed a tendency of worst prognosis. Stimulation of MET-positive gastric cancer cells with live H. pylori bacteria directly up-regulated MET phosphorylation and activated MET downstream signals such as p44/42MAPK and Akt, conferring cell proliferation and anti-apoptotic activity. In conclusion, positive staining for MET4 was useful for predicting poor prognosis of gastric cancers with H. pylori infection. H. pylori stimulated MET-positive gastric cancers and activated downstream signaling, thereby promoting cancer proliferation and anti-apoptotic activity. These results support the importance of H. pylori elimination from gastric epithelial surface in clinical therapy. This article is protected by copyright. All rights reserved.

  2. ABO blood group system and gastric cancer: a case-control study and meta-analysis.

    PubMed

    Wang, Zhiwei; Liu, Lei; Ji, Jun; Zhang, Jianian; Yan, Min; Zhang, Jun; Liu, Bingya; Zhu, Zhenggang; Yu, Yingyan

    2012-10-17

    This study focuses on the association between the ABO blood group system and the risk of gastric cancer or Helicobacter pylori infection. The data for the ABO blood group was collected from 1045 cases of gastric cancer, whereby the patient underwent a gastrectomy in Ruijin Hospital, Shanghai. The information on the ABO blood group from 53,026 healthy blood donors was enrolled as control. We searched the Pubmed database on the relationship between ABO blood groups and gastric cancer risk for meta-analysis. In our case-control study, the risk of gastric cancer in blood group A was significantly higher than that in non-A groups (O, B and AB) (odd ratio, OR1.34; 95% confidential interval, CI 1.25-1.44). Compared with non-O groups (A, B and AB), individuals with blood group O demonstrated a reduced risk of gastric cancer (OR = 0.80; 95% CI 0.72-0.88). The proportion of H. pylori infection in blood group A individuals was significantly higher than that in non-A blood groups (OR = 1.42; 95% CI 1.05-1.93). We further combined our data with the published data of others, and crossreferenced the risk of gastric cancer with the blood type, finding consistent evidence that gastric cancer risk in the blood A group was higher than that in the non-A groups (OR = 1.11; 95% CI 1.07-1.15), and that blood type O individuals were consistently shown gastric cancer risk reduction (OR = 0.91; 95% CI 0.89-0.94). Our study concluded that there was a slightly increased risk of gastric cancer in blood group A individuals, and people with blood type A are more prone to be infected by H. pylori than other ABO blood type individuals, whereas, a slightly decreased risk of gastric cancer was identified in blood type O individuals.

  3. Long-term trends and survival analysis of esophageal and gastric cancer in Yangzhong, 1991-2013

    PubMed Central

    Xue, Hengchuan; Yao, Jun

    2017-01-01

    Objective To describe the long-term trends of the incidence, mortality and survival of upper digestive tract cancers in a high-risk area of China. Methods We extracted esophageal and gastric cancer cases diagnosed from 1991 to 2013 through the Yangzhong Cancer Registry and calculated the crude and age-standardized incidence and mortality rates. Cancer trends were calculated using the Joinpoint Regression Program and were reported using the annual percentage change (APC). The cancer-specific survival rates were evaluated and compared between groups using the Kaplan-Meier method and log-rank test. Results The age-standardized incidence rate of esophageal cancer declined from 107.06 per 100,000 person-years (male: 118.05 per 100,000 person-years; female: 97.42 per 100,000 person-years) in 1991 to 37.04 per 100,000 person-years (male: 46.43 per 100,000 person-years; female: 27.26 per 100,000 person-years) in 2013, with an APC of -2.5% (95% confidence interval (CI): -3.4%, -1.5%) for males and -4.9% (95% CI:-5.8%, -3.9%) for females. The age-standardized incidence rate of gastric cancer was 165.11 per 100,000 person-years (male: 225.39 per 100,000 person-years; female: 113.34 per 100,000 person-years) in 1991 and 53.46 per 100,000 person-years (male: 76.51 per 100,000 person-years; female: 32.43 per 100,000 person-years) in 2013, with the APC of -3.6% (95% CI: -4.5%, -2.7%) for males and -4.8% (95% CI: -5.7%, -3.9%) for females. The median survival time was 3.0 years for patients with esophageal or gastric cancer. Cancer cases detected after 2004 had a better prognosis. Conclusions The age-standardized incidence rates of both esophageal and gastric cancer continuously decreased since 1991 through 2013, whereas the mortality rate remained stable before 2004 and significantly declined following the massive endoscopic screening program initiated in 2004. The survival probability of patients with esophageal and gastric cancer has improved obviously in recent decades. PMID

  4. Notch1 directly induced CD133 expression in human diffuse type gastric cancers

    PubMed Central

    Konishi, Hidetomo; Asano, Naoki; Imatani, Akira; Kimura, Osamu; Kondo, Yutaka; Jin, Xiaoyi; Kanno, Takeshi; Hatta, Waku; Ara, Nobuyuki; Asanuma, Kiyotaka; Koike, Tomoyuki; Shimosegawa, Tooru

    2016-01-01

    CD133 is considered as a stem-like cell marker in some cancers including gastric cancers, and Notch1 signaling is known to play an important role in the maintenance and differentiation of stem-like cells. We aimed to investigate whether Notch1 signaling contributes to the carcinogenesis of gastric cancers and CD133 induction. CD133 expression was detected in 51.4% of diffuse type gastric cancers while it was not detected in intestinal type gastric cancers. Similarly, only poorly-differentiated gastric cancer cell lines expressed CD133 and activated-Notch1. Inhibiting Notch1 signaling resulted in decreased CD133 expression, side population cells, cell proliferation and anchorage independent cell growth. Chromatin immunoprecipitation suggested that this Notch1 dependent regulation of CD133 was caused by direct binding of activated-Notch1 to the RBP-Jκ binding site in the 5′ promoter region of CD133 gene. In addition, knocking down RBP-Jκ reduced CD133 induction in activated-Notch1 transfected cells. These findings suggested that Notch1 signaling plays an important role in the maintenance of the cancer stem-like phenotype in diffuse type gastric cancer through an RBP-Jκ dependent pathway and that inhibiting Notch1 signaling could be an effective therapy against CD133 positive diffuse type gastric cancers. PMID:27489358

  5. Fish consumption and the risk of gastric cancer: systematic review and meta-analysis

    PubMed Central

    2011-01-01

    Background Gastric cancer is the fourth most frequently occurring malignancy after lung, breast, and colorectal cancer, and the second most common cause of death from cancer worldwide. Epidemiologic studies have examined the possible association between fish consumption and gastric cancer, but the results were inconclusive. We conducted a systematic review and meta-analysis to examine the association between fish intake and the risk of gastric cancer. Methods PubMed was searched for studies published in English-language journals from 1991 through 2009. We identified 17 epidemiologic studies (15 case-control and 2 cohort studies) that included relative risks (RRs) or odds ratios (ORs) estimates with 95% confidence intervals (CIs) of the relationship between gastric cancer and fish consumption. Data were extracted using standardized data forms. Summary RRs or ORs for the highest versus non/lowest fish consumption levels were calculated using random-effects model. Heterogeneity among studies was examined using Q and I2 statistics. Results In this study, 5,323 cases of gastric cancer and over 130,000 non-cases were included. The combined results from all studies indicated that the association between high fish consumption and reduced gastric cancer risk was not statistically insignificant (RR = 0.87, 95% CI = 0.71-1.07). Conclusions Current evidence indicated that the association between fish consumption and risk of gastric cancer remains unclear. PMID:21247502

  6. Mechanisms for the induction of gastric cancer by Helicobacter pylori infection: aberrant DNA methylation pathway.

    PubMed

    Maeda, Masahiro; Moro, Hiroshi; Ushijima, Toshikazu

    2017-03-01

    Multiple pathogenic mechanisms by which Helicobacter pylori infection induces gastric cancer have been established in the last two decades. In particular, aberrant DNA methylation is induced in multiple driver genes, which inactivates them. Methylation profiles in gastric cancer are associated with specific subtypes, such as microsatellite instability. Recent comprehensive and integrated analyses showed that many cancer-related pathways are more frequently altered by aberrant DNA methylation than by mutations. Aberrant DNA methylation can even be present in noncancerous gastric mucosae, producing an "epigenetic field for cancerization." Mechanistically, H. pylori-induced chronic inflammation, but not H. pylori itself, plays a direct role in the induction of aberrant DNA methylation. The expression of three inflammation-related genes, Il1b, Nos2, and Tnf, is highly associated with the induction of aberrant DNA methylation. Importantly, the degree of accumulated aberrant DNA methylation is strongly correlated with gastric cancer risk. A recent multicenter prospective cohort study demonstrated the utility of epigenetic cancer risk diagnosis for metachronous gastric cancer. Suppression of aberrant DNA methylation by a demethylating agent was shown to inhibit gastric