Enterococcus faecalis provides protection during scavenging in carrion crow ( Corvus corone).

The gut microbiota significantly influences host physiology and provides essential ecosystem services. While diet can affect the composition of the gut microbiota, the gut microbiota can also help the host adapt to specific dietary habits. The carrion crow ( Corvus corone), an urban facultative scavenger bird, hosts an abundance of pathogens due to its scavenging behavior. Despite this, carrion crows infrequently exhibit illness, a phenomenon related to their unique physiological adaptability. At present, however, the role of the gut microbiota remains incompletely understood. In this study, we performed a comparative analysis using 16S rRNA amplicon sequencing technology to assess colonic content in carrion crows and 16 other bird species with different diets in Beijing, China. Our findings revealed that the dominant gut microbiota in carrion crows was primarily composed of Proteobacteria (75.51%) and Firmicutes (22.37%). Significant differences were observed in the relative abundance of Enterococcus faecalis among groups, highlighting its potential as a biomarker of facultative scavenging behavior in carrion crows. Subsequently, E. faecalis isolated from carrion crows was transplanted into model mice to explore the protective effects of this bacterial community against Salmonella enterica infection. Results showed that E. faecalis down-regulated the expression of pro-inflammatory cytokines tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-γ), and interleukin 6 (IL-6), prevented S. enterica colonization, and regulated the composition of gut microbiota in mice, thereby modulating the host's immune regulatory capacity. Therefore, E. faecalis exerts immunoregulatory and anti-pathogenic functions in carrion crows engaged in scavenging behavior, offering a representative case of how the gut microbiota contributes to the protection of hosts with specialized diets.

Increased Expression of LIPC Is Associated with Aggressive Phenotype of Borrmann Type 4 Gastric Cancer.

PURPOSE: To investigate lipase C hepatic type (LIPC) expression in Borrmann type 4 gastric cancer and its correlation with clinical outcome. The biological roles of LIPC in Borrmann type 4 gastric cancer progression were also investigated. METHODS: We determined LIPC expression in 324 primary gastric cancer tissues and 178 matched adjacent non-tumor tissues by immunohistochemistry. We explored the role of LIPC in Borrmann type 4 gastric cancer cell (OCUM-1) migration, invasion, proliferation, cell cycle, and expression of epithelial-mesenchymal transition-related genes by knocking down LIPC expression. RESULTS: LIPC expression was upregulated in Borrmann type 4 gastric cancer tissues compared with other types of gastric cancer and adjacent non-tumor tissues. High LIPC expression correlated with lymph node metastasis, advanced TNM stage, and poor overall survival in Borrmann type 4 gastric cancer patients. Multivariate analysis demonstrated that high LIPC expression was an independent prognostic factor in patients with Borrmann type 4 gastric cancer. By reducing LIPC expression, OCUM-1 cell invasion and migration were suppressed and Snail and MMP2 expression was downregulated, while E-cadherin expression was upregulated. CONCLUSIONS: High LIPC expression correlates with poor clinical outcome and plays an important role in regulating cell migration and invasion in Borrmann type 4 gastric cancer.

The Prognosis Value of Lymphatic Vessel Invasion in pN0 Gastric Cancer Patients with Insufficient Examined Lymph Nodes.

OBJECTIVES: To investigate the prognosis value of lymphatic vessel invasion (LVI) in pN0 gastric cancer patients with insufficient examined lymph nodes (ELNs). METHODS: Clinicopathologic and prognostic data of pN0 gastric cancer patients with insufficient ELNs who underwent radical surgery in our institution were retrospectively studied. RESULTS: Firstly, we confirmed that less than 16 but not less than 30 ELNs were insufficient ELNs in the present study. Of the 350 pN0 patients with < 16 ELNs, 64 patients (18.29%) had LVI. The overall survival (OS) of patients with LVI was significantly poorer than those without LVI. Multivariate analysis suggested that LVI was one of the independent factors predicting prognosis of pN0 patients with < 16 ELNs. Further analyses suggested that there were similar prognoses between pN0 patients with < 16 ELNs who had LVI and pN1 patients, and between pN0 patients with < 16 ELNs who had no LVI and pN0 patients with ≥ 16 ELNs, respectively. Therefore, we proposed a novel pN classification, in which LVI-positive pN0 gastric cancer with < 16 ELNs was classified as pN1 disease. Two-step multivariate analysis demonstrated that the novel pN classification was more suitable for prognostic assessment than the original one. CONCLUSIONS: LVI is a powerful and independent prognostic factor for pN0 gastric cancer patients with < 16 ELNs, and node-negative gastric cancer with < 16 ELNs which had LVI should be considered as node-positive disease. LVI is an effective indicator identifying patients stage migration happens to in pN0 patients with < 16 ELNs.

The prognostic roles of circulating ALDH1+ tumor cell in the patients with non-small cell lung cancer.

Circulating tumor cells can provide important diagnostic and prognostic information of the patients with non-small cell lung cancer (NSCLC). Aldehyde dehydrogenase 1 (ALDH1), a cancer stem cell marker, has been used in various tumors, including NSCLC. In the present study, we isolated the circulating ALDH1+ tumor cells from the NSCLC patients using ALDH1 as a potential marker. Higher percentage of ALDH1+ tumor cells was identified in blood samples from the NSCLC patients compared with normal controls. ALDH1+ cells were correlated with the poor prognosis of these patients by using Kaplan-Meier analysis. In the last, the tumorigenic properties of ALDH1+ tumor cells were determined in vitro and in vivo by using sphere assay and xenograft tumor mouse models. Our in vitro and in vivo experiments demonstrated that ALDH1 could drive the stemness of circulating NSCLC cells. Circulating ALDH1+ cells could be used as a prognostic marker for NSCLC.

Rare upper gastrointestinal hemorrhage of cetuximab: A case report.

RATIONALE: cetuximab, an epidermal growth factor receptor inhibitor, is a targeted therapeutic regimen of colorectal cancers. Several common adverse effects have been found, such as cutaneous or gastrointestinal toxicity. However, according to the articles had been published, upper gastrointestinal bleeding (UGIB) is considered to be rare and its mechanism remains unclear. PATIENT CONCERNS: In this report, we presented a 42-year-old male patient with advanced recto-sigmoid cancer. After palliative operation, the patient suffered from complete upper gastrointestinal (GI) obstruction, which was induced by extensive abdominal metastasis of the tumor. Considering his poor condition, we chose the targeted drug, cetuximab, as his further treatment. But after the application of cetuximab, the UGIB immediately happened twice in this patient. DIAGNOSIS: UGIB, as a rare complication of cetuximab, occured to the patient. INTERVENTIONS: We stopped the bleeding with thrombin, hemocoagulase and somatostatin and suspended the subsequent treatment plan of cetuximab. At the same time, anti-shock treatment was given immediately. OUTCOMES: He was died of respiratory and circulatory failure caused by UGIB and advanced tumor eventually. LESSONS: UGIB should be considered as a rare but severe complication of cetuximab. When cetuximab is applied for patients with advanced colon tumors, more cautions should be required if the patients are accompanied by upper gastrointestinal obstruction. In addition, for those patients who suffered from UGIB recently, cetuximab should be prohibited if the Rockall score ranged > 5 points.

Tbx3 overexpression in human gastric cancer is correlated with advanced tumor stage and nodal status and promotes cancer cell growth and invasion.

The objective of the current study was to investigate the expression pattern of Tbx3 and its clinicopathological significance in patients with gastric cancer. The expression pattern of Tbx3 in gastric cancer tissues and adjacent noncancerous surface epithelia and mucosal glands was detected by immunohistochemistry. Tbx3 was found to be overexpressed in 46 of 98 human gastric cancer samples, and this correlated with advanced clinical stage, tumor stage, and nodal status. In addition, in the SGC-7901 gastric cancer cell line, Tbx3 overexpression by plasmid transfection promoted growth and invasion. Conversely, depleting Tbx3 expression by small-interfering RNA inhibited proliferation and invasion in BGC-823 cell line. Moreover, Tbx3 accelerated cell cycle progression at the G1/S boundary. Tbx3 also regulated epithelial-to-mesenchymal transition (EMT) to promote cell invasion by repressing E-cadherin expression and increasing expression levels N-cadherin, vimentin. These results indicate that in gastric cancer, Tbx3 plays an important role and might be a useful therapy target.

The roles of serum CXCL16 in circulating Tregs and gastrointestinal stromal tumor cells.

Gastrointestinal stromal tumors (GIST) are the most common sarcomas of the digestive system. Abnormal expression of CXCL16 and its sole receptor, CXCR6, has been demonstrated in many cancers. However, no studies have shown the relationship between CXCL16 or CXCR6 expression and GIST. In this study, we detected CXCL16 and CXCR6 expression in GIST patient samples by using immunohistochemistry analysis and Western blot analysis. Serum CXCL16 level was determined by using enzyme-linked immunosorbent assay. Circulating Tregs were isolated by using flow cytometry. MTT assay, cell cycle assay, and transwell assay were used to test the effects of recombinant CXCL16 on Tregs and GIST cells in vitro. The levels of CXCL16 and CXCR6 protein were higher in cancer tissues than in normal tissues. Serum CXCL16 level and circulating Tregs were higher in GIST patients than that in the healthy volunteers. CXCL16, CXCR6, serum CXCL16, and circulating Tregs were significantly associated with a decreased survival time of patients. Relative to control cells, high concentration recombinant CXCL16 treated Tregs and GIST cells exhibited lower proliferation and mobility rates as assessed by MTT assay and transwell assay, respectively. Taken together, CXCL16 was observed to mediate the inhibitory effects in Tregs and GIST cells, and these involved suppression of the MEK/ERK signaling pathway.

Endoglin overexpression mediates gastric cancer peritoneal dissemination by inducing mesothelial cell senescence.

Peritoneal dissemination (PD), which is highly frequent in gastric cancer (GC) patients, is the main cause of death in advanced GC. Senescence of human peritoneal mesothelial cells (HPMC) may contribute to GC peritoneal dissemination (GCPD). In this study of 126 patients, we investigated the association between Endoglin expression in GC peritoneum and the clinicopathological features. The prognosis of patients was evaluated according to Endoglin and ID1 expression. In vitro, GC cell (GCC)-HPMC coculture was established. Endoglin and ID1 expression was evaluated by Western blot. Cell cycle and HPMC senescence were analyzed after harvesting HPMC from the coculture. GCC adhesion and invasion to HPMC were also assayed. Our results showed that positive staining of Endoglin (38%) was associated with a higher TNM stage and higher incidence of GCPD (both P < .05). Kaplan-Meier analysis showed that the patients who were Endoglin positive had a shorter survival time compared with Endoglin-negative patients (P = .02). Using the HPMC and GCC adherence and invasion assay, we demonstrated that transforming growth factor beta 1 (TGF-ß)1-induced HPMC senescence was attenuated by silencing the Endoglin expression, which also prevented GCC attachment and invasion. Our study indicated a positive correlation between Endoglin overexpression and GCPD. Up-regulated Endoglin expression induced HPMC senescence via TGF-ß1 pathway. The findings suggest that Endoglin-induced HPMC senescence may contribute to peritoneal dissemination of GCCs.

Canstatin induces apoptosis in gastric cancer xenograft growth in mice through the mitochondrial apoptotic pathway.

Canstatin, the non-collagenous domain of collagen type IV α-chains, belongs to a series of collagen-derived angiogenic inhibitors. In this study, the inhibitory effect of recombinant canstatin on tumour growth was investigated using a gastric cancer xenograft model. The volume and weight of tumours in mice treated with canstatin were lower than that in mice treated with PBS. Accordingly, the survival rate of these mice was significantly higher than that of mice bearing tumours treated with PBS. Moreover, valuable insight into the mechanisms mediated by canstatin was obtained.

Association of polymorphisms in interleukin-18 and interleukin-28B genes with outcomes of hepatitis B virus infections: a meta-analysis.

Several polymorphisms in the interleukin-18 (IL-18) and nterleukin-28B (IL-28B) genes have been reported to influence hepatitis B virus (HBV) infection. However, the published findings have been conflicting. We conducted meta-analyses of randomized, controlled trials to address the association of IL-18 or IL-28B polymorphisms and the outcomes of HBV infection. Weipu, Wanfang, CNKI, MEDLINE, PubMed, EMBASE, and Cochrane Library databases were employed to search for citations using the MeSH terms as "interleukin-18"/"interleukin-28B" AND "HBV" AND "gene" AND "polymorphism" without any restriction in language and publication year. Meta-analysis was conducted by RevMan 5.0 software. The results showed that the IL28B rs8099917 AA genotype (AA vs AC + CC: odds ratio (OR) = 0.63, 95 % confidence interval (CI) = 0.46-0.87) was associated with a decreased risk of hepatocellular carcinoma (HCC). Carriage of IL28B rs12979860 CC genotype was associated with an increased risk for developing liver cirrhosis among patients with HBV infection (CC vs CT + TT: OR = 1.39, 95 % CI = 1.04-1.85). Further well-designed large studies are warranted to confirm the mechanisms by which these are involved in these outcomes of HBV infection.

Bag-3 expression is involved in pathogenesis and progression of colorectal carcinomas.

Bcl-2-associated athanogene 3 (Bag-3) belongs to a member of the Hsc70 binding co-chaperone Bag-family proteins and has critical roles in protein homeostasis, cell survival, actin organization, cell adhesion, cell motility and tumor metastasis. To clarify the role of Bag-3 in colorectal carcinogenesis and subsequent development, its expression was examined by immunohistochemistry (IHC) and in situ hybridization (ISH) on tissue microarrays containing colorectal carcinomas, adenomas, non-neoplastic mucosa (NNM) and metastatic carcinomas in lymph node and liver. Colorectal carcinoma tissue and cell lines were studied for Bag-3 expression by RT-PCR, Western blot and immunofluorescence. The results demonstrated that Bag3 was distinctly expressed in Colo201, Colo205, DLD-1, HCT-15, HCT-116, HT-29, KM-12, SW480, SW620, and WiDr at both mRNA and protein levels. Carcinoma showed stronger Bag-3 expression than adjacent NNM by IHC and Western blot (P<0.05), while its mRNA had the opposite by real-time PCR and ISH (P<0.05). Metastatic carcinoma more frequently expressed Bag-3 mRNA in lymph node and liver than in primary carcinoma (P<0.05). Immunohistochemically, Bag-3 expression was seen to gradually decrease from carcinoma, adenoma to NNM (P<0.05). There was a positive correlation between Bag-3 expression and TNM staging and GRP94 expression (P<0.05), but no relationship to patient age or sex, tumor size, depth of invasion, lymphatic or venous invasion, lymph node metastasis, differentiation or prognosis of colorectal carcinomas (P<0.05). Our study indicated that aberrant Bag-3 expression might be involved in colorectal adenoma-adenocarcinoma sequence and subsequent progression.

Beclin 1 expression is an independent prognostic factor for gastric carcinomas.

Beclin 1, an important autophagy-related protein in human cells, is involved in autophagy, differentiation, anti-apoptosis, and cancer progression, which is increased during periods of cell stress and extinguished during the cell cycle. In order to clarify the role of Beclin 1 in gastric carcinogenesis and subsequent progression, its expression was examined by immunohistochemistry and in situ hybridization (ISH) on tissue microarrays containing gastric carcinomas, adjacent non-neoplastic mucosa, and metastatic lymph node. Gastric carcinoma tissue and cell lines were studied for Beclin 1 expression by Western blot or RT-PCR, respectively. The results demonstrated that Beclin 1 was distinctively expressed in GES-1, AGS, BGC-823, GT-3 TKB, HGC-27, KATO-III, MGC-803, MKN28, MKN45, SCH, SGC-7901, or STKM-2 at both mRNA and protein levels. However, Beclin 1 mRNA was highly expressed in gastric carcinoma than matched mucosa by real-time PCR and ISH (P < 0.05). Beclin 1 expression was negatively related to distant metastasis and poor prognosis of gastric carcinoma (P < 0.05). Beclin 1 was highly expressed in male than female patients with gastric carcinoma (P < 0.05). The 65-year-elder patients with gastric carcinoma had higher Beclin 1 expression than the younger ones (P < 0.05). The diffuse-type carcinomas showed less Beclin 1 expression than intestinal- and mixed-type ones (P < 0.05). In intestinal-type gastric carcinoma, Beclin 1 expression was inversely associated with venous invasion, lymph node metastasis, and tumor-node-metastasis (TNM) staging (P < 0.05). Kaplan-Meier analysis indicated that Beclin 1 expression was positively linked to favorable prognosis of the patients with overall and intestinal-type carcinoma (P < 0.05). Cox's proportional hazard model indicated that venous invasion, lymph node metastasis, distant metastasis, TNM staging, and Beclin 1 expression were independent prognostic factors for gastric carcinomas (P < 0.05). It was suggested that aberrant Beclin 1 expression is closely linked to pathogenesis, metastasis, and differentiation of gastric carcinoma. Beclin 1 expression might be employed to indicate the favorable prognosis of gastric carcinomas as an independent factor.

COL4A3 expression correlates with pathogenesis, pathologic behaviors, and prognosis of gastric carcinomas.

COL4A3 protein belongs to type IV collagen family and is closely linked to kidney diseases and cancer. To clarify the roles of COL4A3 in gastric carcinogenesis and subsequent progression, its expression was examined by immunohistochemistry on tissue microarrays containing gastric carcinomas, adjacent intestinal metaplasia, pure intestinal metaplasia, and gastritis. Gastric carcinoma tissue and cell lines were studied for COL4A3 expression by Western blotting and reverse transcription-polymerase chain reaction. We found that COL4A3 was differentially expressed in GES-1, AGS, BGC-823, GT-3 TKB, HGC-27, KATO-III, MGC-803, MKN28, MKN45, SCH, SGC-7901, and STKM-2 at both messenger RNA and protein levels. Carcinomas showed statistically lower COL4A3 expression than matched nonneoplastic mucosa (P < .05). Expression was strong in intestinal metaplasia in comparison with gastritis and carcinoma (P < .05). There was greater COL4A3 expression in carcinoma than gastritis (P < .05). Expression of COL4A3 protein was positively correlated with tumor size, lymphatic invasion, venous invasion, and TNM stage (P < .05). There was more COL4A3 expression in diffuse than in intestinal-type carcinomas regardless of invasion into the muscularis propria (P < .05). Histologically, all signet ring cell (n = 43) and mucinous (n = 12) carcinomas showed COL4A3 expression. Kaplan-Meier analysis indicated that COL4A3 expression was negatively associated with a favorable prognosis of overall, advanced, and intestinal-type gastric carcinomas (P < .05). Aberrant COL4A3 expression might play an important role in the pathogenesis and subsequent progression of gastric carcinoma. COL4A3 overexpression might be used as a marker of gastric intestinal metaplasia and mucinous and signet ring cell carcinoma.

Role and clinicopathologic significance of CXC chemokine ligand 16 and chemokine (C-X-C motif) receptor 6 expression in gastric carcinomas.

The chemokine ligand CXC chemokine ligand 16 and its receptor chemokine (C-X-C motif) receptor 6 are up-regulated in many types of cancer and give rise to more aggressive behavior by regulating proliferation and angiogenesis. To clarify the role and clinicopathologic significance of CXC chemokine ligand 16 and chemokine (C-X-C motif) receptor 6 expression in gastric carcinoma, their expression was examined by immunohistochemistry of tissue microarrays containing gastric carcinoma and nonneoplastic mucosa, reverse transcription-polymerase chain reaction, and Western blotting and by enzyme-linked immunosorbent assay to determine the CXC chemokine ligand 16 concentration in serum. Expression was compared with the clinicopathologic features of the carcinomas. All carcinoma and epithelial cells showed CXC chemokine ligand 16 and chemokine (C-X-C motif) receptor 6 messenger RNA expression to various degrees. Among 28 pairs of gastric carcinoma and normal tissues, there was higher CXC chemokine ligand 16 expression in carcinoma than in adjacent mucosa (P < .05), whereas the converse was true for chemokine (C-X-C motif) receptor 6 (P < .05). Nuclear CXC chemokine ligand 16 expression correlated inversely with the depth of invasion, lymphatic invasion, Union Internationale Contre le Cancer stage, and favorable prognosis. The serum CXC chemokine ligand 16 concentration was lower in male patients or patients 55 years or older than in female or younger patients, respectively (P < .05). Patients with lymphatic invasion or mixed-type carcinoma showed lower CXC chemokine ligand 16 concentrations than those with no lymphatic invasion or with diffuse-type carcinoma (P < .05). Aberrant expression of CXC chemokine ligand 16 and chemokine (C-X-C motif) receptor 6 might be involved in gastric carcinogenesis. The expression and serum concentration of CXC chemokine ligand 16 could indicate the aggressiveness and prognosis of gastric carcinomas.

The roles of REIC gene and its encoding product in gastric carcinoma.

REIC is downregulated in immortalized cell lines compared with the parental normal counterparts. It may inhibit colony formation, tumor growth and induce apoptosis. Here, gastric carcinoma or epithelial cells transfected with REIC-expressing plasmid, its siRNA or treated with recombinant REIC were subjected to the phenotypes' measurement or related molecules' detection. REIC expression was examined in gastric carcinomas by RT-PCR, western blot and immunohistochemistry. REIC overexpression or treatment resulted in a low karyoplasmic ratio and proliferation, G1 arrest, high apoptosis, low migration, invasion or lamellipodia formation in AGS cells. REIC knockdown caused the opposite in GES-1 cells. Anti-REIC antibody blocked the effects of REIC overexpression on proliferation, G1/S progression and apoptosis. Ectopic REIC expression downregulated the expression of ß-catenin, phosphorylated S6K (Thr389), phosphorylated Akt1/2/3 (Ser473), cyclin D2 and E, WAVE2 and upregulated phosphorylated mTOR (Ser2448) expression and the mRNA level of Akt1, Akt2, mTOR, Raptor and Rictor in AGS cells. REIC expression was negatively associated with tumor size, lymph node metastasis, dedifferentiation or poor prognosis of carcinoma. The serum REIC level was significantly higher in healthy individuals than the carcinoma patients and inversely linked to tumor size by ELISA. The possible mechanisms underlying the forced REIC overexpression or recombinant REIC mediated the reversal of the aggressive phenotypes of gastric carcinoma cells are to downregulate ß-catenin and WAVE2 expression and to alter other related target proteins. Downregulated REIC expression was closely linked to aggressive behaviors and poor prognosis of gastric carcinoma.

Clinicopathological and prognostic significance of MUC-2, MUC-4 and MUC-5AC expression in japanese gastric carcinomas.

BACKGROUND: The mucin components of the gastric gel layer function as a protective and lubricating factor against luminal acid and proteolytic enzymes. Alteration of mucin expression in gastric preneoplastic and neoplastic lesions has suggested potential roles in neoplastic processes. This study aimed to assess the clinicopathological and prognostic significance of MUC-2, MUC-4 and MUC-5AC in Japanese gastric cancer. METHODS: Expression of MUC-2, -4 and -5AC was evaluated on tissue microarrays of gastric carcinomas and adjacent non-cancerous mucosa specimens by immunohistochemistry and compared with clinicopathological parameters and survival time of the patients. RESULTS: The three mucins were found to be expressed to a lesser extent in gastric carcinomas in comparison with non-cancerous mucosa (p<0.05). MUC-2 expression was negatively correlated with tumor size, depth of invasion, and TNM staging of gastric cancer (p<0.05), while that of MUC-5AC was negatively associated with the depth of invasion, venous invasion, lymph node metastasis and TNM staging (p<0.05), but positively with MUC-4 and MUC-2 expression (p<0.05). There was higher MUC-2 expression in intestinal- than diffuse-type carcinomas (p<0.05). Kaplan-Meier analysis indicated no relationship between expression of the three mucins and the cumulative survival rate of patients, even stratified according to the depth of invasion (p>0.05). CONCLUSION: Down-regulated expression of MUC-2, -4 and -5AC may be involved in pathogenesis, invasion, metastasis or differentiation of gastric carcinoma. Their altered expression might therefore be employed as an indicator of pathobiological behavior.

[The secreted level of REIC protein in gastric carcinoma and its role of proliferation inhibition].

AIM: To detect secretory REIC content in serum from the patients with gastric carcinoma and cell culture medium of gastric carcinoma cell lines, and determine the effects of recombinant REIC on proliferation of gastric carcinoma cells. METHODS: ELISA was employed to determine REIC content in serum and supernatant, and WST-8 to detect the proliferation of gastric carcinoma cells. RESULTS: The secretion level of REIC was obviously decreased in serum form gastric carcinoma, compared with healthy individuals (P<0.05) and inversely correlated with the tumor size of gastric carcinomas (P<0.05). The REIC content was lower in supernatant from gastric carcinoma cells than that in epithelial cells (P<0.05). After the transfection of REIC-expressing plasmid, the concentration of REIC was increased in supernatant from AGS (P<0.05). The proliferation of AGS and BGC-823 could be inhibited by recombinant REIC (P<0.05). CONCLUSION: REIC expression of secretion type decreased in gastric carcinoma cells, and inhibited the proliferation of gastric carcinoma cells. REIC protein might be employed as a good marker or target for the early diagnosis, biological and gene therapy of gastric carcinoma.

The altered expression of ING5 protein is involved in gastric carcinogenesis and subsequent progression.

ING5 can interact with p53, thereby inhibiting cell growth and inducing apoptosis. To clarify the roles of ING5 in gastric tumorigenesis and progression, its expression was examined by immunohistochemistry on a tissue microarray containing gastric nonneoplastic mucosa (n = 119), dysplasia (n = 50), and carcinomas (n = 429), with its comparison with clinicopathologic parameters of the carcinomas. ING5 expression was analyzed in gastric carcinoma tissues and cell lines (MKN28, MKN45, AGS, GT-3 TKB, and KATO-III) by Western blot and reverse transcriptase-polymerase chain reaction. ING5 protein was found to distribute to the nuclei of gastric carcinoma cells with similar messenger RNA levels. An increased expression of ING5 messenger RNA was observed in gastric carcinoma in comparison with paired mucosa (P < .05). Lower expression of nuclear ING5 was detected in gastric dysplasia and carcinoma than that in nonneoplastic mucosa (P < .05). Gastric nonneoplastic mucosa and metastatic carcinoma showed more expression of cytoplasmic ING5 than did gastric carcinoma and dysplasia (P < .05). Nuclear ING5 expression was negatively correlated with tumor size, depth of invasion, lymph node metastasis, and clinicopathologic staging (P < .05), whereas cytoplasmic ING5 was positively associated with depth of invasion, venous invasion, lymph node metastasis, and clinicopathologic staging (P < .05). Nuclear ING5 was more expressed in older than younger carcinoma patients (P < .05). There was a higher expression of nuclear ING5 in intestinal-type than diffuse-type carcinoma (P < .05), whereas it was the converse for cytoplasmic ING5 (P < .05). Survival analysis indicated that nuclear ING5 was closely linked to favorable prognosis of carcinoma patients (P < .05), albeit not independent. It was suggested that aberrant ING5 expression may contribute to pathogenesis, growth, and invasion of gastric carcinomas and could be considered as a promising marker to gauge aggressiveness and prognosis of gastric carcinoma.

The antitumor activity of exogenous and endogenous canstatin on colorectal cancer cells.

Colorectal cancer is the third most common malignancy and the third-leading cause of cancer-related deaths worldwide. In the last several years, recombinant DNA technology has made cancer gene therapy feasible in the clinic. In our studies, we used both exogenous and endogenous canstatin, a type IV collagen genetically distinct product. We detected the effects of canstatin on colorectal cancer cells HCT-15 and HCT-116. DAPI staining, FCM and migration analyse were used to detect the apoptotic cells, cell cycle and mobility. As shown in the results, the apoptotic cell numbers (p<0.05) and G1 arrest cell numbers (p<0.05) were higher than in the non- treatment case. The mobility of the cells was also decreased obviously (p<0.05). Simultaneously, combination effects of exogenous and endogenous canstatin were identified.

The pathobiological behaviors and prognosis associated with Japanese gastric adenocarcinomas of pure WHO histological subtypes.

Japan is a high-risk region for gastric carcinoma with a comparatively early stage and favorable prognosis. To clarify the pathobiological behaviors and prognosis of Japanese gastric adenocarcinoma, we analyzed the clinicopathological characteristics of different WHO subtypes of carcinomas. The expression of ki-67, CPP32, p53, FHIT, maspin, parafibromin, GRP78, GRP94, EMMPRIN, VEGF, P-GSK3beta-ser9, fascin, cortactin, Arp2, Arp3 MUC-2, MUC-5AC and MUC-6 was examined using immunohistochemistry and tissue microarrays. The majority of cases were well-, poorly-, or moderately-differentiated subtype, whereas the minority were papillary or signet ring cell carcinoma (SRC). Patients with poorly-differentiated or SRC carcinoma were predominantly young and female. Poorly-differentiated and mucinous carcinomas were larger, with deeper invasion, more venous or lymphatic invasion, frequent lymph node involvement and peritoneal dissemination, or higher staging. The SRC group exhibited weaker expression of ki-67, CPP32, p53, parafibromin, GRP78, GRP94, P-GSK3beta-ser9, VEGF or cortactin. The moderately-differentiated subtype exhibited lower expression of FHIT and Arp3 positivity. The poorly-differentiated group showed weaker expression of CPP32, EMMPRIN, MUC-2, MUC-5AC, and MUC-6. Survival analysis indicated that the patients with poorly-differentiated or mucinous subtypes had a lower cumulative survival rate than those with papillary, well-, moderately-differentiated, or SRC carcinomas (P<0.05). The age, invasive depth, lymphatic invasion, peritoneal dissemination, and WHO classification were independent prognostic factors for carcinoma patients (P<0.05). It was suggested that poorly-differentiated and mucinous subtypes are more aggressive and of unfavorable prognosis among Japanese gastric carcinomas. Lower levels of proliferation and apoptosis, as well as alterations in tumor suppressor genes, mucin production and ER stress protein played important roles in the pathogenesis of poorly-differentiated and SRC carcinomas.