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Chordin (CHRD) is a secreted protein important in early development, yet a role for CHRD in human disease has not been identified. In this study we investigated CHRD in cancer and normal adult tissues using the wealth of genome-wide data available in public databases. We found that Chordin is amplified in the DNA of specific cancers such as lung squamous cell and others, although copy number variation did not strictly correlate with higher mRNA expression. In some cancers, such as renal and stomach carcinomas, increased CHRD expression significantly correlated with poor survival. In normal adult human tissues, CHRD mRNA was highest in hepatocytes. Crossveinless-2/BMPER, a component of the Chordin morphogenetic pathway expressed at the opposite side in embryos, was expressed in liver stellate cells. This raises the intriguing possibility that a BMP gradient might be established in the extracellular matrix of the space of Disse that surrounds portal sinusoid capillaries.

Chordin (CHRD) is a secreted protein important in early development, yet a role for CHRD in human disease has not been identified. In this study we investigated CHRD in cancer and normal adult tissues using the wealth of genome-wide data available in public databases. We found that Chordin is amplified in the DNA of specific cancers such as lung squamous cell and others, although copy number variation did not strictly correlate with higher mRNA expression. In some cancers, such as renal and stomach carcinomas, increased CHRD expression significantly correlated with poor survival. In normal adult human tissues, CHRD mRNA was highest in hepatocytes. Crossveinless-2/BMPER, a component of the Chordin morphogenetic pathway expressed at the opposite side in embryos, was expressed in liver stellate cells. This raises the intriguing possibility that a BMP gradient might be established in the extracellular matrix of the space of Disse that surrounds portal sinusoid capillaries.

Abstract Background To investigate the role of achaete-scute complex-like 2 (ASCL2) in stomach adenocarcinoma (STAD), we analyze whether ASCL2 suppression could retard cancer development and further observe the relevance between ASCL2 and inflammation via Toll-like receptor 4 (TLR4) activation in STAD, both in vitro and in vivo. Methods Proliferation, development, inflammation, and apoptosis in STAD are observed using sh-ASCL2 lentivirus via TLR4 activation in vitro and in vivo. The relationship between ASCL2 and inflammation is analyzed. Western blotting of ASCL2 with the target protein of immune-associated cells is performed. The prognosis of STAD and associated ASCL2 mutation are analyzed. Results The ASCL2 level in STAD tumor tissues is increased, compared to normal tissues, and brings a worse prognosis. The ASCL2 shows a negative correlation with inflammation, and TLR4 reveals a positive correlation with gastric cancer. ASCL2 expression is high in MGC803 cells. Sh-ASCL2 could reduce STAD development by decreasing proliferation, tumor volume, and biomarker levels and increasing apoptosis in vitro and in vivo. The inflammatory role of ASCL2 is regulated through TLR4 activation. ASCL2 levels may be related to CNTNAP3, CLIP1, C9orf84, ARIH2, and IL1R2 mutations; positively correlated with M2 macrophage and T follicular helper cell levels; negatively correlated with neutrophil, dendritic cell, monocyte, CD8 T cell, and M1 macrophage levels; and involved in STAD prognosis. Conclusions The ASCL2 may adjust inflammation in STAD through TLR4 activation and may be associated with related immune cells. ASCL2 is possibly an upstream target factor of the TLR4 signaling pathway.

Background: To investigate the role of achaete-scute complex-like 2 (ASCL2) in stomach adenocarcinoma (STAD), we analyze whether ASCL2 suppression could retard cancer development and further observe the relevance between ASCL2 and inflammation via Toll-like receptor 4 (TLR4) activation in STAD, both in vitro and in vivo. Methods: Proliferation, development, inflammation, and apoptosis in STAD are observed using sh-ASCL2 lentivirus via TLR4 activation in vitro and in vivo. The relationship between ASCL2 and inflammation is analyzed. Western blotting of ASCL2 with the target protein of immune-associated cells is performed. The prognosis of STAD and associated ASCL2 mutation are analyzed. Results: The ASCL2 level in STAD tumor tissues is increased, compared to normal tissues, and brings a worse prognosis. The ASCL2 shows a negative correlation with inflammation, and TLR4 reveals a positive correlation with gastric cancer. ASCL2 expression is high in MGC803 cells. Sh-ASCL2 could reduce STAD development by decreasing proliferation, tumor volume, and biomarker levels and increasing apoptosis in vitro and in vivo. The inflammatory role of ASCL2 is regulated through TLR4 activation. ASCL2 levels may be related to CNTNAP3, CLIP1, C9orf84, ARIH2, and IL1R2 mutations; positively correlated with M2 macrophage and T follicular helper cell levels; negatively correlated with neutrophil, dendritic cell, monocyte, CD8 T cell, and M1 macrophage levels; and involved in STAD prognosis. Conclusions: The ASCL2 may adjust inflammation in STAD through TLR4 activation and may be associated with related immune cells. ASCL2 is possibly an upstream target factor of the TLR4 signaling pathway. [ABSTRACT FROM AUTHOR]

Abstract: Objective To screen out the ferroptosis-related prognostic genes of gastric cancer and to construct a ferroptosis genes-related prognostic model through bioinformatics method. Methods â‘ To screen out ferroptosis-related genes associated with prognosis of gastric cancer: ：The gene microarray and related clinical data of gastric cancer were download from The Cancer Genome Atlas(TCGA) database. R software was used to screen out ferroptosis-related differentially expressed genes between cancer and paracancer tissues, as well as prognostic genes related to overall survival. The intersectional genes were obtained and their biological functions were analyzed. The Gene Set Enrichment Analysis (GSEA) software (https//www. gsea-msigdb.org/gsea/index.jsp) was utilized to analyze the enrichment pathways of ferroptosis genes related to the prognosis of gastric cancer of high expression. â‘¡ To construct and verify prognostic model of gastric cancer: A gene-related prognostic model of gastric cancer was constructed and validated by Lasso Cox regression analysis. Results Compared with paracancer tissues, the expression of 29 ferroptosis-related genes increased and the expression of 12 ferroptosis-related genes decreased in the gastric cancer tissues. Among them，NFE2L2 and SLC1A5 were related to the prognosis of gastric cancer. NFE2L2 mainly participated in the biological functions such as detection of chemical stimulus and regulation of membrane potential, while SLC1A5 mainly participated in the biological functions such as metal ion transport and regulation of protein serine and threonine kinase activity. The prognostic model of these genes was e(-0.315×NFE2L2)+(-0.161×SLC1A5). The area under ROC curve predicted by this model was 0. 561, 0. 587 and 0. 615 in the Abstract: Objective To screen out the ferroptosis-related prognostic genes of gastric cancer and to construct a ferroptosis genes-related prognostic model through bioinformatics method. Methods ①To screen out ferroptosis-related genes associated with prognosis of gastric cancer: ：The gene microarray and related clinical data of gastric cancer were download from The Cancer Genome Atlas(TCGA) database. R software was used to screen out ferroptosis-related differentially expressed genes between cancer and paracancer tissues, as well as prognostic genes related to overall survival. The intersectional genes were obtained and their biological functions were analyzed. The Gene Set Enrichment Analysis (GSEA) software (https//www. gsea-msigdb.org/gsea/index.jsp) was utilized to analyze the enrichment pathways of ferroptosis genes related to the prognosis of gastric cancer of high expression. ② To construct and verify prognostic model of gastric cancer: A gene-related prognostic model of gastric cancer was constructed and validated by Lasso Cox regression analysis. Results Compared with paracancer tissues, the expression of 29 ferroptosis-related genes increased and the expression of 12 ferroptosis-related genes decreased in the gastric cancer tissues. Among them，NFE2L2 and SLC1A5 were related to the prognosis of gastric cancer. NFE2L2 mainly participated in the biological functions such as detection of chemical stimulus and regulation of membrane potential, while SLC1A5 mainly participated in the biological functions such as metal ion transport and regulation of protein serine and threonine kinase activity. The prognostic model of these genes was e(-0.315×NFE2L2)+(-0.161×SLC1A5). The area under ROC curve predicted by this model was 0. 561, 0. 587 and 0. 615 in the [ABSTRACT FROM AUTHOR]

To investigate the role of cell division cycle associated 7 (CDCA7) in stomach carcinoma, detect whether CDCA7 knockdown could regulate the development of stomach carcinoma, and further observe the relationship between CDCA7 and inflammation through TLR4/NF‐κB signaling pathway in stomach adenocarcinoma (STAD) in vitro and in vivo. TIMER2.0, Kaplan–Meier plotter, Target Gene, and GEPIA systems were used to predict the potential function of CDCA7. Western blot and immunohistochemistry was used to analyze the expression of CDCA7 at different tissue or cell lines. The proliferation, development, inflammation, and apoptosis of STAD in vitro and in vivo were observed by using CDCA7 knockdown lentivirus through TLR4 suppression by its inhibitor. Bioinformatics analysis of CDCA7 with inflammation and western blot of CDCA7 with target protein of immune‐associated cells were observed by using CDCA7 knockdown lentivirus in vivo. Finally, the prognosis and associated of CDCA7 in some gene mutations of STAD was observed by Target Gene system. CDCA7 expression in STAD tumor tissue was higher than the normal. The CDCA7 expression in tumor or MGC803 cells was increased. Furthermore, CDCA7 knockdown lentivirus could inhibit STAD development in vitro and in vivo through weakening tumor cells proliferation, reducing tumor volume and biomarker levels, and then increasing apoptotic level. CDCA7 is possibly able to regulate inflammation in STAD through TLR4/NF‐κB signaling pathway. Furthermore, CDCA7 may be related with mast cells and the upstream target factor of TLR4/NF‐κB signaling pathway in inflammation. These results may provide a new strategy to stomach carcinoma development by regulating inflammation. [ABSTRACT FROM AUTHOR]

Recently, the number of long-term survivors of = 5 years after stomach carcinoma resection is increasing in Japan. The clinical courses of 4,883 patients who underwent stomach carcinoma resection were retrospectively reviewed to investigate the cause of death including multiple primary cancers (MPC) and delayed stomach carcinoma recurrence among long-term survivors of = 5 years. Of 3,061 patients who survived for = 5 years, 1,203 patients (39.3%) were dead after 5 years survival, including 299 patients (24.9%) who died of MPC. Of 84 patients (7.0%) who died of recurrent stomach carcinoma, 25 patients were newly diagnosed = 5 years postoperative. The most common site of MPC was lung in 124 patients, and 347 patients (44.7%) had a smoking-related MPC, including 124 lung, 63 esophagus, 62 head and neck, and 98 other cancers. We examined the prognostic differences in 527 patients with MPC according to the diagnosis time. In 325 patients of long-term survivors in whom MPC was diagnosed = 5 years postoperative, 5-year survival rate and the median survival time after diagnosis were 35.1% and 17.7 months, respectively. This outcome was significantly poorer than that of 160 patients in whom MPC was diagnosed within 5 years postoperative (58.5% and 62.7 months, P < 0.0001). In conclusion, MPC accounted for approximately a quarter of the cause of death in long-term survivors. Lifestyle instructions including smoking cessation are important. Periodical cancer screening allows the early asymptomatic diagnosis and may contribute to a decrease in cancer mortality of MPC in long-term cancer survivors. [ABSTRACT FROM AUTHOR]

Background Neuromyelitis optica ( NMO) is an autoimmune astrocytopathy associated with anti-aquaporin-4 ( AQP4). The development of NMO in the setting of cancer suggests that AQP4 autoimmunity might in some cases be paraneoplastic. Case presentation We report an 85-year-old woman who developed a right optic neuritis and a longitudinally extensive transverse myelitis associated with AQP4 autoantibodies after the relapse of stomach cancer. Histopathological observations in several case reports have led to the hypothesis that the NMO associated with the malignancy is caused by an autoimmunity against abnormally expressed AQP4 on tumor cells. However, we found no AQP4 antigen on the cancer cells in our resected tissues. Our findings did not support the concept of a paraneoplastic process in the narrow sense. Conclusions The exact mechanisms of cancer-related NMO, which might be multifactorial, remain controversial. [ABSTRACT FROM AUTHOR]

Objective To investigate tlie effects of detection of BRCA1, ERCC1, TYMS and TUBB3 genes in guidance of individual chemotherapy for patients with advanced gastric cancer. Methods Eighty patients with advanced gastric cancer were randomly divided into the individual group (TG) ( n = 40) and the control group (CG) ( n =40). The protein and mRNA expression levels of BRCA1 , ERCC1 , TYMS and TUBB3 genes were measured by immunohistochemical method and branched-DNA liquid chip quantitative analysis, respectively. Different chemotherapies were administered according to the mRNA expression levels of the four genes, while DCF or mDCF chemotherapy was directly applied to the control group. Overall response rate (ORR) , adverse effects, and progression-free survival ( PFS) were observed and analyzed. Results After two cycles, ORR were 41.9% in the TG and 39. 4% in the CG. KPS clinical benefit rates were 54. 8% in the TG and 54.5% in the CG. There were no statistical differences between two groups (both P >0.05). After four cycles, ORR were 45% in the TG and 54. 5% in the CG, and KPS clinical benefit rates were 75. 0% in the TG and 72. 7% in the CG. There were no statistical differences between two groups (both P>0. 05). The rates of adverse effects in grade 3 to 4 were 26.3% and 55.9% in the TG and CG, respectively. There was no statistical difference between the two groups ( P > 0.05) , but adverse effects were significantly less serious in TG than in CG after dose reduction and chemotherapy discontinuance (/><().05). PFS were7.7 m (95 %CI: 5.97-9.42) and 6. 6 m (95% Cl: 5.59-7.6) in the TG and CG. There was no statistically significant difference between the two groups (/J >0.05). Conclusion Compared with DCF or mDCF chemotherapy, using their BRCA1 , ERCC1 , TYMS and TUBB3 mRNA expression levels in guidance of the individual chemotherapy for patients with advanced gastric cancer may reduce the adverse effects, but there are no statistical differences in the ORR and PFS. [ABSTRACT FROM AUTHOR]

The laparoscopic surgery in gastric cancer is applied with increasing frequency nowadays; noticeable reports come mainly from Korea and Japan with satisfactory results. This review presents briefly the issue by evaluating its role. A PubMed search of relevant articles published up to 2010 was performed to identify current information. Most data come from Far East, where gastric cancer occurs more often, and the proportion of early gastric cancer is high. Laparoscopic approach includes both the diagnostic laparoscopy and laparoscopic resection. Laparoscopic gastrectomy has currently limited application for gastric cancer in the West; it is not widely accepted and raises important considerations necessitating the planning of multicentre randomised control trials based mainly on the long-term results.

Primary bladder tumor is a frequent urological malignancy, whereas the incidence of secondary bladder tumor from a distant organ is quite rare. Secondary bladder neoplasms represent 1% of all malignant bladder tumors, of which distant metastases from stomach account for about 4% of cases. We present the case of a 30-year-old male who underwent partial gastrectomy for Signet-ring cell carcinoma of the stomach and presented 2 years later with hematuria. On computerized tomography scan, a bladder tumor was found which was resected cystoscopically. The histopathological examination revealed secondary Signet-ring cell adenocarcinoma of the urinary bladder.

Hepatoid adenocarcinoma of the stomach (HAS) is a rare distinct variant of gastric carcinoma with earlier metastases and worse prognosis compared to the more common intestinal types. It is often misdiagnosed as hepatocellular carcinoma, especially when primary HAS is insignificantly anatomically abnormal, produces high alpha-fetoprotein and develops early liver metastasis. In this case we show the significance of dual-time-point F-fluorodeoxyglucose positron emission tomography (PET)/computed tomography (CT) in accurately diagnosing and staging HAS. [ABSTRACT FROM AUTHOR]

Aims To clarify the relationship between the Epstein–Barr virus (EBV) and gastric carcinoma with lymphoid stroma (GCLS) in Koreans, and to characterize the EBV-positive GCLS. Methods and results EBV infection was examined using EBER in-situ hybridization and polymerase chain reaction in 45 cases of GCLS among Koreans, and in 292 consecutive cases of gastric carcinomas without lymphoid stroma (non-GCLS) as controls. EBV infection was found in 30 tumours (67%) of GCLS and 10 tumours (3.4%) of non-GCLS (P < 0.05). EBV-positive GCLS was more prevalent in males, poorly differentiated histological type and diffuse type in Lauren's classification, and tended to be located more in the middle third of the stomach than EBV-negative GCLS (P < 0.05). p53 overexpression was observed in 22% of GCLS (17% of EBV-positive GCLS and 33% of EBV-negative GCLS), and 34% of non-GCLS (EBV-positive GCLS vs. non-GCLS: P = 0.056). The survival of the patient with GCLS was not correlated with EBV infection or p53 immunoexpression (follow-up period: 11–97 months). Conclusions GCLS in Koreans is strongly associated with EBV infection. The prognosis in GCLS is not dependent upon either the status of EBV infection or the status of p53 immunoexpression. [ABSTRACT FROM AUTHOR]

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Adjacent organ invasion by stomach carcinoma on computed tomography (CT) was studied. CT images of tumors and their adjacent organs, whose invasion was assessed at surgery, were retrospectively analyzed in 51 gastric cancer patients. An absence of fat planes or an irregularity of the border between the tumor and adjacent organs was not found to be significantly related with invasion. The mean densities of the region of interest (ROI) set at the border were greater at the invasion sites (60.0±38.1) than at noninvasion sites (35.6±55.5) ( P<0.05). The standard deviation of the densities in the ROI was not affected by invasion. The discriminant function determined invasion to the pancreas, liver, and colon with an accuracy of 75%, 61% and 78%, respectively. In diagnosing the invasion of stomach cancer on CT, the conventional criteria were not practical, while a quantitative analysis of the density in the ROI with high resolution CT was considered to improve the accuracy. [ABSTRACT FROM AUTHOR]

Intratumoral injections of 10 mg cells walls from Propionibacterium granulosum strain KP-45 (PG) were applied in 14 patients with advanced, metastatic stomach (five cases) and colorectal (nine cases) adenocarcinoma. Each patient had his own 'twin' control. All patients received no other anticancer treatment, except analgetics and/or palliative surgery. Treatment with PG resulted in partial regression of tumors accompanied by improvement of the clinical state of these patients as well as the reappearance of normal values in blood count biochemical parameters. In each pair of twin cases, survival of the PG-treated patient was longer than the untreated control. The mean survival of PG-treated patients was 23.5 months (4 of 14 patients being still alive after 2.5 years follow-up), while all control patients died with a mean survival period of 6.4 months. The difference between these two patient groups of about 17 month is significant ( p>0.01). [ABSTRACT FROM AUTHOR]

The cellular and molecular pathology of gastric cancer and its precursors are reviewed and discussed. Gastric carcinogenesis is a multistep phenomenon, beginning with precancerous conditions. Among these, adenoma is a direct precursor, because of the dysplastic nature of its cells. However, gastric adenoma is relatively rare. Chronic atrophic gastritis (CAG) is the most common precancerous condition, in which intestinal metaplasia often occurs. Carcinoma develops in CAG through stages of hyperplasia and dysplasia involving both metaplastic and non-metaplastic glands. Molecular alterations, including replication error and p53 and APC gene mutation and aneuploidy have been found in some of these conditions, confirming their role in carcinogenesis. Carcinomas of the stomach are heterogeneous in cellular composition. Both intestinal and gastric types of cells are found in all types of tumors, indicating the unique characteristics of gastric cancer. Many molecular lesions have been found in gastric carcinomas. Basic changes involve replication errors, telomerase activity, and aberrant CD44 transcripts. Many other changes often show differences in the frequency of their occurrence between the two major histological types of gastric carcinoma: well differentiated versus poorly differentiated, or intestinal type versus diffuse type. The timing and frequency of these changes in the stomach differ from the timing and frequency in colonic carcinogeneis. Pathological evaluation remains reliable and meaningful, in basic research as well as clinical management. To obtain correlation with molecular alterations, the need for detailed pathologic classification of gastric carcinoma is recognized, taking into account its biologic behavior and grades of cell differentiation. The cellular and molecular pathology of gastric cancer and its precursors are reviewed and discussed. Gastric carcinomas are unique in their heterogeneity in both cellular composition and molecular changes. [ABSTRACT FROM AUTHOR]

CEA was studied in paraffin sections from 50 cases of colonic and 50 cases of gastric adenocarcinoma using immunoperoxidase and immunofluorescence techniques. CEA was positive more frequently in colonic (86 per cent) than in stomach carcinoma (76 per cent). Immunoperoxidase was found to be the more sensitive technique for the detection of CEA in both organs. The non-neoplastic peritumoral colonic mucosa was more often CEA positive than was the peritumoral gastric mucosa. CEA was found more often, and the intensity of the staining was stronger in well-differentiated colonic and gastric carcinoma than it was in poorly differentiated carcinoma. No relation was found between the presence of CEA in colonic and gastric carcinoma and the stages of the disease. CEA was detected more frequently in carcinomas of the left colon than in carcinomas of the right colon. [ABSTRACT FROM AUTHOR]

Primary bladder tumor is a frequent urological malignancy, whereas the incidence of secondary bladder tumor from a distant organ is quite rare. Secondary bladder neoplasms represent 1% of all malignant bladder tumors, of which distant metastases from stomach account for about 4% of cases. We present the case of a 30-year-old male who underwent partial gastrectomy for Signet-ring cell carcinoma of the stomach and presented 2 years later with hematuria. On computerized tomography scan, a bladder tumor was found which was resected cystoscopically. The histopathological examination revealed secondary Signet-ring cell adenocarcinoma of the urinary bladder. [ABSTRACT FROM AUTHOR]

Endoscopic ultrasonography /EUS/ is a minimally invasive imaging diagnostic method with exceptional accuracy in diagnosing oesophageal and stomach tumour distension. Objective of this retrospective -- prospective study is to determine accuracy of staging assessment and the invasion of oesophagus and stomach tumour with EUS compared to intraoperative findings. Study included patients who had oesophagus and stomach carcinoma verified by routine endoscopy and histopathology findings in the period 2003 -2005 at the Clinic for Gastroenterology and Hepatology, Clinical Centre University of Sarajevo, whereas 18 of them had oesophageal carcinoma stage T1-T4 located on superior, medial and inferior third, and 24 patients had stomach carcinoma T0- T3/ stomach corpus and antrum. 15 (74%) patients with oesophageal carcinoma were operable. 3 (24%) patients were excluded from the study because they had stenosis inferior third of oesophagus, and 23 (100%) patients with stomach carcinoma. They were operated by two surgeons. Intraoperative findings of oesophageal carcinoma showed that EUS sensitivity for all stages was 88.8%, while it was 75% sensitive for stomach carcinoma and 80% specific. Results were statistically assessed with X² test. Conclusion Application of EUS in the staging assessment of oesophageal and stomach carcinoma, especially for stage T, represents a gold standard and its use is scientifically grounded for preoperative application of planning further treatment of these two malignancies compared to intraoperative findings. [ABSTRACT FROM AUTHOR]

Presented is a rare case of bilateral neoplastic metastases to the ovaries (Krukenberg’s tumors) and to the fundus of the uterus which occurred in the course of stomach cancer in a 46-year-old female who was treated surgically in the Department of Obstetrics and Gynecology of the Regional Hospital in Slupsk. The patient was admitted secondary to bilateral ovarian masses. Her past medical history included peptic ulcer disease for a few years, confirmed by gastroscopic biopsy in July of 2000. The surgery performed in our department revealed bilateral ovarian tumors, each measuring about 10 cm in diameter, which were completely removed along with the fundus of the uterus. The intraoperative histologic diagnosis was ovarian cancer. No other macroscopic neoplastic changes were found during the surgery. During surgical removal of the gastrocolic ligament a group of enlarged lymph nodes at the greater curvature of the stomach in the proximity of the spleen was incidentally noticed. The intraoperative histology of the lymph nodes described metastatic neoplasia. Another intraoperative biopsy was also performed of the stomach because of atypical clinical presentation of the ovarian cancer. The pathologic diagnosis was stomach cancer. Upon the consultation with pathologists it was concluded that the primary tumor came from the stomach while the changes in the ovaries and lymph nodes were metastatic. Thus, the surgery consisted of total hysterectomy as well as removal of the stomach along with the spleen, gastrocolic ligament and greater omentum. The distal esophagus was anastomosed with the loop of jejunum. The final result of histologic exam confirmed the location of the primary neoplastic tumor in the stomach with metastases to both ovaries, the body of uterus, and lymph nodes at the greater curvature of the stomach. [ABSTRACT FROM AUTHOR]