Down-regulated miR-9 and miR-433 in human gastric carcinoma

<p>Abstract</p> <p>Background</p> <p>MircoRNAs(miRNAs) are short, endogenously non-coding RNAs. The abnormal expression of miRNAs may be valuable for the diagnosis and treatment of tumors.</p> <p>Methods</p> <p>To screening the special miRNAs in gastric carcinoma, expression level of miRNAs in gastric carcinoma and normal gaster samples were detected by miRNA gene chip. Then, the expressions of miR-9 and miR-433 in gastric carcinoma tissue and SGC7901 cell line were validated by qRT-PCR. GRB2 and RAB34, targets of miR-433 and miR-9 respectively, were detected by Western blot.</p> <p>Results</p> <p>We found 19 miRNAs and 7 miRNAs were down-regulated and up-regulated respectively. Compared with normal gaster samples, our data showed that miR-9 and miR-433 were down-regulated in gastric carcinoma. Meanwhile, we also found that miR-433 and miR-9 regulated the expression levels of GRB2 and RAB34 respectively.</p> <p>Conclusion</p> <p>Our data show miR-9 and miR-433 was down-regulated in gastric carcinoma. The targets of miR-433 and miR-9 were tumor-associated proteins GRB2 and RAB34 respectively. This result provided the related information of miRNAs in gastric carcinoma.</p

Dynamic expression of CEACAM7 in precursor lesions of gastric carcinoma and its prognostic value in combination with CEA

<p>Abstract</p> <p>Background</p> <p>The significance of carcinoembryonic antigen-related cell adhesion molecule 7 (CEACAM7) expression in gastric carcinoma and precancerous lesions and its correlation with CEA expression has rarely been previously investigated.</p> <p>Methods</p> <p>CEACAM7 and CEA expression was detected by immunohistochemistry in consecutive sections of 345 subjects with gastric carcinoma and precancerous lesions. Laser confocal analysis was performed to determine CEACAM7 and CEA localization. Correlation between CEACAM7 and CEA expression with clinicopathological parameters was statistically analyzed.</p> <p>Results</p> <p>CEACAM7 expression correlated with pathologic grading (P = 0.006), Lauren's classification (P = 0.023), and CEA expression (Spearman R = 0.605, P < 0.001) in gastric carcinoma. CEACAM7 co-localized with CEA predominantly in the cytoplasmic membrane of cancerous cells. CEA expression was correlated with lymph node metastasis (P = 0.031). CEACAM7 and CEA expression increased progressively from precursor lesions to gastric carcinomas. A combination of CEACAM7 and CEA expression was determined to be an independent predictor for patients with gastric carcinoma by multivariate analysis (P = 0.001).</p> <p>Conclusions</p> <p>CEACAM7 expression correlates with tumor differentiation and CEA expression in gastric carcinoma. CEACAM7 and CEA expression may synergistically promote gastric carcinogenesis. Combined CEACAM7 and CEA expression analysis can be a useful postoperative predictor for patients with gastric carcinoma.</p

Relationship between p53 expression and gastric cancers in cardia and antrum

Background: The mutations in p53 gene and accumulation of p53 protein are the most common genetic events in gastric carcinomas. The present study was conducted to compare the frequency of p53 gene overexpression in a consecutive series of adenocarcinomas arising from the cardia and the antrum. This study also evaluates the associations of this gene expression with demographic and clinicopathologic findings (age, sex, histology, and grade of tumor). Methods: Retrospective analysis was performed on 111 patients with gastric cancer who had undergone upper gastrointestinal endoscopies in 5th Azar Medical Center (northeastern, Iran), during 1998-2005. The series comprised of 25 patients with cardia adenocarcinoma and 86 patients with antral adenocarcinoma. p53 alteration (nuclear p53 overexpression) was detected by immunohistochemistry. Results: Nuclear p53 overexpression was found in 14 (56%) out of the 25 and 27 (31.3%) out of the 86 patients with cardia and antral adenocarcinomas, respectively. p53 gene overexpression was significantly more frequent in adenocarcinomas of the cardia than the antrum. There were no differences in the clinicopathologic characteristics of the tumors between p53-positive and p53-negative cases in both types of the cancer. Conclusion: This study shows that p53 alterations correlate well with gastric location, and they are more frequent in adenocarcinoma of the cardia than the antrum. This result reinforce the hypothesis that the cancers of the lower esophagus and upper stomach have distinct epidemiologic, pathogenesis, and molecular characteristics from that observed in cancers of the lower part of the stomach

Epidemiology and Characteristics of Gastric Carcinoma in Childhood : An Analysis of Data from Population-Based and Clinical Cancer Registries

(1) Background: Gastric carcinoma is an exceptionally rare tumor in childhood. Little is known about the etiology, epidemiology, and clinical features of pediatric gastric carcinomas. This analysis aimed to fill this gap by increasing knowledge about the occurrence of gastric carcinoma in childhood. (2) Material and methods: Data from gastric carcinoma cases diagnosed between 2000 and 2017/2018 were retrieved from the Surveillance, Epidemiology, and End Results Program (SEER) and the German Center for Cancer Registry Data. Data from patients <20 years of age were analyzed for patient- and tumor-related characteristics. In addition, clinical data from patients with gastric carcinoma registered in the German Registry for Rare Pediatric Tumors (STEP) were analyzed for diagnostics, therapy, and outcome. (3) Results: Ninety-one cases of gastric carcinoma, mainly in adolescents, were identified in the epidemiologic cancer registries. Among patients with recorded staging data, advanced tumor stages were common (66.7%). Within the follow-up period covered, 63.7% of patients with clinical follow-up data died. Eight pediatric patients with gastric carcinoma were enrolled in the STEP registry, among whom two were patients with hereditary CDH1 mutations and another was a patient with Peutz–Jeghers syndrome. Three patients were found to have distinctly decreased immunoglobulin concentrations. All four patients in whom complete resection was achieved remained in remission. Three of the other four patients died despite multimodal therapy. (4) Conclusions: A combination of Helicobacter pylori infection and tumor predisposition and/or immunodeficiency appears to promote the development of gastric carcinoma in childhood. While patients with localized disease stages have a good chance of achieving durable remission through complete resection, patients with stage IV carcinomas face a dismal prognosis, highlighting the need to develop new strategies such as mutation-guided treatments

Gastric Cancer at a University Teaching Hospital in Northwestern Tanzania: A Retrospective Review of 232 Cases.

Despite marked decreases in its incidence, particularly in developed countries, gastric cancer is still the second most common tumor worldwide. There is a paucity of information regarding gastric cancer in northwestern Tanzania. This study was undertaken to describe our experience, in our local setting, on the management of gastric cancer, outlining the clinicopathological and treatment outcome of these patients and suggesting ways to improve the treatment outcome. This was a retrospective study of histologically confirmed cases of gastric cancer seen at Bugando Medical Centre between January 2007 and December 2011. Data were retrieved from patients' files and analyzed using SPSS computer software version 17.0. A total of 232 gastric cancer patients were enrolled in the study, representing 4.5% of all malignancies. The male to female ratio was 2.9:1. The median age of patients was 52 years. The majority of the patients (92.1%) presented late with advanced gastric cancer (Stages III and IV). Lymph node and distant metastasis at the time of diagnosis was recorded in 31.9% and 29.3% of cases, respectively. The antrum was the most frequent anatomical site (56.5%) involved and gastric adenocarcinoma (95.1%) was the most common histopathological type. Out of 232 patients, 223 (96.1%) patients underwent surgical procedures for gastric cancer of which gastro-jejunostomy was the most frequent performed surgical procedure, accounting for 53.8% of cases. The use of chemotherapy and radiotherapy was documented in 56 (24.1%) and 12 (5.1%) patients, respectively. Postoperative complication and mortality rates were 37.1% and 18.1%, respectively. According to multivariate logistic regression analysis, preoperative co-morbidity, histological grade and stage of the tumor, presence of metastases at the time of diagnosis was the main predictors of death (P <0.001). At the end of five years, only 76 (32.8%) patients were available for follow-up and the overall five-year survival rate was 6.9%. Evidence of cancer recurrence was reported in 45 (19.4%) patients. Positive resection margins, stage of the tumor and presence of metastasis at the time of diagnosis were the main predictors of local recurrence (P <0.001). Gastric cancer in this region shows a trend towards relative young age at diagnosis and the majority of patients present late with an advanced stage. Lack of awareness of the disease, poor accessibility to health care facilities and lack of screening programs in this region may contribute to advanced disease at the time of diagnosis. There is a need for early detection, adequate treatment and proper follow-up to improve treatment outcome

Influence of perineural invasion in predicting overall survival and disease-free survival in patients With locally advanced gastric cancer

Background The aim of the present study was to evaluate the prognostic significance of perineural invasion (PNI) in locally advanced gastric cancer patients who underwent D2 gastrectomy and adjuvant chemotherapy. Methods The records of a series of 103 patients undergoing D2 gastrectomy with curative intent combined with adjuvant chemotherapy from January 2004 to December 2014 were retrospectively reviewed. Results PNI was positive in 47 (45.6%) specimens. The 1-, 3-, and 5-year overall survival rates were 81%, 55%, and 42%, respectively. The 1-, 3-, and 5-year disease-free survival (DFS) rates were 76%, 57%, and 49%, respectively. A multivariate analysis showed that age number of positive lymph nodes, T stage, and PNI were independently associated with overall survival. Regarding DFS, the multivariate analysis showed that only PNI was independently associated with DFS. Conclusions PNI and T stage and positive lymph nodes are independent markers of poor prognosis in patients with gastric cancer. PNI should be incorporated in the postoperative staging system for planning follow-up after surgery and in our opinion to propose more aggressive postoperative therapies in PNI-positive patients

Metastatic carcinoma of the colon similar to Crohn's disease: a case report.

A 68-year-old Japanese man with a history of linitis plastica carcinoma of the stomach and subsequent gastrectomy 8 years previously presented with lower abdominal pain. Radiological and endoscopic examinations showed multiple submucosal nodular lesions similar to Crohn's disease in the ileocecal area. A firm diagnosis could not be made after initial multiple biopsies. Finally, a submucosal biopsy revealed adenocarcinoma. The ileocecal lesion was diagnosed as a recurrence because of the histological findings, which included mucosal preservation, a similarity with the histologic type of stomach carcinoma, and atypical immunoreactivity for primary colon carcinoma; the lesion was negative for both cytokeratin 7 and cytokeratin 20. In cases where metastatic carcinoma of the colon is suspected, we recommend early consideration of a submucosal biopsy.</p

Bilateral metastasis to the femoral head as the only manifestation of recurrence of gastric adenocarcinoma: a case report

BACKGROUND: Metastases to the bone as the sole manifestation of recurrence of a gastric carcinoma are extremely rare. CASE REPORT: We herein report the case of a 63-year-old man operated a year and a half before for a poorly differentiated gastric carcinoma affecting the fundus, who developed bilateral metastasis to the femoral head as the sole manifestation of recurrence. He was treated with radiotherapy to control pain with a poor response and both femoral heads had to be eventually resected. CONCLUSIONS: We review the literature on the rare occurrence of osseous metastasis from gastric carcinoma and comment briefly on the therapeutic options for these cases

Missense mutations in the perforin (PRF1) gene as a cause of hereditary cancer predisposition

Perforin, a pore-forming toxin released from secretory granules of NK cells and CTLs, is essential for their cytotoxic activity against infected or cancerous target cells. Bi-allelic loss-of-function mutations in the perforin gene are invariably associated with a fatal immunoregulatory disorder, familial haemophagocytic lymphohistiocytosis type 2 (FHL2), in infants. More recently, it has also been recognized that partial loss of perforin function can cause disease in later life, including delayed onset FHL2 and haematological malignancies. Herein we report a family in which a wide range of systemic inflammatory and neoplastic manifestations have occurred across three generations. We found that disease was linked to two missense perforin gene mutations (encoding A91V, R410W) that cause protein misfolding and partial loss of activity. These cases link the partial loss of perforin function with some solid tumours that are known to be controlled by the immune system, as well as haematological cancers. Our findings also demonstrate that perforin gene mutations can contribute to hereditary cancer predisposition

Risk factors in gastric cancer

STATE OF THE ART: Gastric cancer (GC) is still a major health problem worldwide due to its frequency, poor prognosis and limited treatment options. At present prevention is likely to be the most effective means of reducing the incidence and mortality from this disease. The most important etiological factors implicated in gastric carcinogenesis are diet and Helicobacter pylori (H. pylori) infection. High intake of salted, pickled or smoked foods, as well as dried fish and meat and refined carbohydrates significantly increased the risk of developing GC while fibers, fresh vegetables and fruit were found to be inversely associated with GC risk. Epidemiological investigations (retrospective, case-control and prospective) and several meta-analyses have demonstrated that concurrent or previous H. pylori infection is associated with an increased risk of GC in respect to uninfected people. H. pylori colonizes gastric mucosa where it induces a complex inflammatory and immune reaction that on time leads to a severe mucosal damage i.e., atrophy, intestinal metaplasia (IM) and dysplasia. The risk of GC is closely related to the grade and extension of gastric atrophy, IM and dysplasia. PERSPECTIVES AND CONCLUSIONS: Today a plausible program for GC prevention means: (1) a correct dietary habit since childhood increasing vegetables and fruit intake, (2) a decrease of H. pylori spread improving family and community sanitation and hygiene, (3) a search and treat H. pylori strategy in offspring of GC, (4) a search and treat H. pylori strategy in patients with chronic atrophic gastritis and intestinal metaplasia (IM), (5) a careful endoscopic and histologic follow-up if precancerous lesions persist irrespective of H. pylori eradication