[Clinical Features of Collagenous Gastritis].

Objective To analyze the clinical characteristics of collagenous gastritis (CG) and provide evidence for the precise diagnosis and treatment of CG.Methods Published case reports and case series were collected from PubMed,CNKI,and Wanfang Med Online with the key words of collagenous gastritis,collagenous gastroduodenitis,collagenous gastrointestinal diseases,and gastric mucosal nodules.The demographic and clinical information of each case was collected.Results According to the extent of collagen deposition in the digestive tract,94 CG cases included in this study were assigned into upper digestive tract (UDT)-CG,total digestive tract (TDT)-CG and other groups.The UDT-CG group included 52 cases (57.69% females and 42.31% males) with a median age of 14.50 (11.00,25.75) years old.There were 17 cases in the TDT-CG group,including 70.59% females and 29.41% males,with a median age of 15.00 (9.50,48.50) years old.The other group contained 25 cases,(64.00% females and 36.00% males) with a median age of 25.00 (15.50,59.50) years old.The main clinical manifestations in the UDT-CG group were anemia (59.62%) and diarrhea (17.31%),and those in the TDT-CG group were anemia (29.41%) and diarrhea (94.12%).The nodular appearance of gastric mucosa was observed in 75.00% cases in the UDT-CG group and 35.29% cases in the TDT-CG group.In the initial treatment,symptomatic therapy and hormonal therapy respectively relieved the symptoms in 75.00% (30/40) and 100% (3/3) cases in the UDT-CG group and 57.14% (4/7) and 83.33% (5/6) cases in the TDT-CG group.In the retreatment,symptomatic therapy and hormone therapy respectively achieved the remission rates of 100.00% (3/3) and 88.89% (8/9) in the UDT-CG group and 80.00% (4/5) and 66.67% (2/3) in the TDT-CG group.Conclusions CG,a rare disease of gastric collagen deposition,mainly occurs in young patients,and females are more susceptible than males.The clinical manifestations of CG are nonspecific,and anemia,abdominal pain,diarrhea,weight loss,and gastrointestinal bleeding are the common symptoms of CG.Nodular appearance of gastric mucosa is a relatively specific endoscopic feature of CG.There is no standardized treatment for CG.Symptomatic treatment is commonly adopted to improve the quality of life of the patients,and hormones can be added when necessary.

Clinical Characteristics and Prognostic Factors of Small Intestine Angiosarcoma: a Retrospective Clinical Analysis of 66 Cases.

BACKGROUND/AIMS: Primary angiosarcoma of the small intestine is a rare neoplasia, and there are limited data from systematic analyses. The aim of this study is to describe the clinical and pathological characteristics in addition to the prognostic factors for this rare neoplasia. METHODS: We retrospectively collected the clinical records and prognostic information of 66 patients with small intestine angiosarcoma reported between 1970 and 2017. We used the Chi-square test, the log-rank test, and Cox regression analyses to evaluate the data. RESULTS: There were 66 patients diagnosed with small intestine angiosarcoma. The onset age ranged from 24-92 years old. There were 24 patients diagnosed before the year 2000, and 42 patients were diagnosed after 2000. The data indicated that 49 cases were diagnosed as primary disease, and the remaining 15 cases were secondary disease. The main clinical symptoms were nonspecific and included gastrointestinal (GI) bleeding and abdominal pain. Additionally, we found multi-center foci were one of the characteristics of this disease. Radiation-induced small intestine angiosarcoma (RSIA) is a special type of disease with a similar prognosis. This type was more frequent in females and decreased after the year 2000. We also found that GI bleeding was less common in RSIA cases. The log-rank test results revealed that old-age, poor differentiation, and GI bleeding were associated with worse prognosis. Surgical treatment showed a trend toward a prolonged survival time. However, the result was not statistically significant. Our results show treatment with adjuvant therapy improved prognosis. The multivariate Cox analysis demonstrated adjuvant therapy was an independent indicator of a favorable outcome in small intestine angiosarcoma patients. CONCLUSION: Pay attention to the unexplained gastrointestinal bleeding could lead to a faster diagnosis and control of small intestine angiosarcoma. Furthermore, treatments including adjuvant therapy can effectively improve the prognosis.

Overexpressed PTOV1 associates with tumorigenesis and progression of esophageal squamous cell carcinoma.

PTOV1 has been demonstrated to play an extensive role in many types of cancers. This study takes the first step to clarify the potential relationship between esophageal squamous cell carcinoma and PTOV1 expression and highlight the link between PTOV1 and the tumorigenesis, progression, and prognosis of esophageal squamous cell carcinoma. PTOV1 expression was detected by quantitative reverse transcription polymerase chain reaction and western blotting or immunohistochemical staining in esophageal squamous cell carcinoma cell lines, esophageal squamous cell carcinoma tissues, and its paired adjacent non-cancerous tissues. Moreover, we have analyzed the relationship between PTOV1 expression and clinicopathological features of esophageal squamous cell carcinoma. Survival analysis and Cox regression analysis were used to assess its prognostic significance. We found that PTOV1 expression was significantly higher in the esophageal squamous cell carcinoma cell lines and tissues at messenger RNA level (p < 0.001) and protein level (p < 0.001). Gender, tumor size, or differentiation was tightly associated with the PTOV1 expression. Lymph node involvement (p < 0.001) and TNM stage (p < 0.001) promoted a high PTOV1 expression. A prognostic significance of PTOV1 was also found by Log-rank method, and the overexpression of PTOV1 was related to a shorter OS and DFS. Multiple Cox regression analysis indicated overexpressed PTOV1 as an independent indicator for adverse prognosis. In conclusion, this study takes the lead to demonstrate that the overexpressed PTOV1 plays a vital role in the tumorigenesis and progression of esophageal squamous cell carcinoma, and it is potentially a valuable prognostic predicator and new chemotherapeutic target for esophageal squamous cell carcinoma.

The apoptotic effect and associated signalling of HSP90 inhibitor 17-DMAG in hepatocellular carcinoma cells.

Primary liver cancer is one of the highly malignant tumours. The traditional surgery, chemotherapy and radiation therapy only established 6% of 5-year survival rate in HCC (hepatocellular carcinoma). Therefore there is an urgent need to develop new therapeutic strategies. HSP90 (heat shock protein 90) is one of the important molecular chaperones and was identified with high expression in the primary liver cancer. In this study, we evaluated the therapeutic effect of specific HSP90 inhibitor 17-DMAG (17-dimethylaminoethylamino-17-demethoxy geldanamycin) in HCC cells. The time and concentration effects of 17-DMAG were investigated in HCC cells. Cell proliferation was measured by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide] assay and cell counting. Apoptosis was detected by flow cytometry with staining of Annexin V-FITC/PI (propidium iodide). The protein levels of survivin, cyclin D1, p53 and NF-κB (nuclear factor κB) were measured by Western blotting. 17-DMAG inhibited the proliferation of HCC cells in a time- and concentration-dependent manner. Treatment with 400 nmol/l 17-DMAG for 48 h significantly induced early-stage apoptosis (22.4%). Conversely, it induced less late-stage apoptosis (3.03%). The 5 mg/l of cisplatin induced significantly less early-stage apoptosis (6.5%), but similar proportion of late-stage apoptosis (4.89%) compared with 17-DMAG. Inhibition of HSP90 activity by 400 nmol/l 17-DMAG decreased protein levels of survivin, cyclin D1 and NF-κB protein levels, whereas increased p53 protein level. HSP90 plays a key role in HCC cell growth and survival through regulation of survivin, cyclin D1, p53 and nucleus NF-κB protein levels and the specific HSP90 inhibitor 17-DMAG can play a therapeutic role in HCC treatment.

Inhibition of Pim-1 kinase ameliorates dextran sodium sulfate-induced colitis in mice.

BACKGROUND: Pim-1 kinase is involved in the control of cell growth, differentiation and apoptosis. Recent evidence suggests that Pim kinases play a role in immune regulation and inflammation. However, the role of Pim-1 kinase in inflammatory bowel diseases (IBD) remains unclear. AIMS: The aims of this study were to explore the role of Pim-1 kinase in the pathology of IBD and to assess whether inhibiting Pim-1 kinase may be of therapeutic benefit as a treatment regimen for IBD. METHODS: Colitic mouse model was established by the induction of dextran sodium sulfate. The expression of Pim-1 in the colonic samples of control and colitic mice was examined. Furthermore, the mice were treated with Pim-1inhibitor (PIM-Inh), then the body weight and colon inflammation were evaluated, and the production of cytokines including IFN-γ, IL-4, TGF-ß and IL-17 in colon tissues was determined by ELISA. The expression of T cell master transcription factors T-bet, ROR-γt, GATA-3 and Foxp3 and Nuclear factor κB (NF-κB) and inducible nitric oxide synthase in colon tissues was detected by real-time PCR and western blot. Finally, the effect of LPS on Pim-1 expression and the effects of PIM-Inh on LPS-induced upregualtion of p65 and TNF-α in RAW264.7 cells were examined by real-time PCR and western blot. RESULTS: Pim-1 expression was correlated with the degree of mucosal inflammation in vivo, and it was significantly induced by LPS in vitro. PIM-Inh had protective effects on acute colitis in vivo. Mechanistically, PIM-Inh reduced the proinflammatory immune response through the inhibition of the overactivation of macrophages and the down-regulation of excessive Th1- and Th17-type immune responses. Furthermore, PIM-Inh could skew T cell differentiation towards a Treg phenotype. CONCLUSIONS: Pim-1 kinase is involved in mucosal injury/inflammation and Pim-1 kinase inhibitor may provide a novel therapeutic approach for IBD.

[Clinical and prognostic features of the patients with esophageal squamous cell carcinomas as a first primary malignancy].

Objective: To retrospectively analyze the clinical characters and prognosis of the patients with Esophageal Squamous Cell Carcinomas as First Primary Malignancy (ESCCFPM), which will help us better understand the relationship between Esophageal Squamous Cell Carcinoma (ESCC) and other cancers, and to provide appropriate research evidence for the clinical diagnosis and treatment. Methods: The clinicopathological and follow-up data of 540 Patients with ESCCFPM between January 1, 2004 and December 31, 2016 were collected from the Surveillance, Epidemiology and End Results (SEER) database of National Cancer Institute. The Kaplan-Meier method was used to determine Overall Survival (OS) curves of ESCC patients, and the Log-Rank test was used to estimate differences in survival. The Cox proportional hazards models were adopted for the prognosis analyses. Results: Regarding the number of multiple primary malignancies (MPMs), 491 had two malignancies, 42 had three malignancies and 7 had four malignancies. ESCCFPM is more common among males. The high incidence age is between 61 and 80 years old. Tumors of the respiratory system (36.9%), were the most common MPMs followed by digestive system (35.2%) and reproductive system (8.9%). The 1-year, 3-year, 5-year OS rates for patients with ESCCFPM were 76.9%, 50.4% and 38.9%, respectively. The age of the ESCC diagnosed, T stage, time of occurrence, carcinoma number, lymph node dissection, surgery, radiotherapy and chemotherapy were the prognostic factor of overall survival for ESCCFPM patients. Age, race, T stage, time of occurrence surgery and radiotherapy were independent prognostic factors for the whole cohort by multivariate survival analysis. Conclusion: ESCCFPM,mainly two-lesion cancer, is most commonly found in respiratory system and digestive systems. Enhanced follow-up of respiratory and digestive tumors in ESCCFPM patients aged 61-80 may help identify multiple primary malignancies. Surgery, radiotherapy and chemotherapy may improve overall survival for ESCCFPM patients.

[The diagnostic value of double-balloon enteroscopy in 67 cases with obscure abdominal pain].

OBJECTIVE: To evaluate the diagnostic valve of double balloon enteroscopy in patients with obscure abdominal pain and analyze the etiology of chronic abdominal pain resulted from enteral diseases. METHODS: Sixty-seven cases with chronic abdominal pain underwent a previous negative gastroscopy, colonoscopy, gastrointestinal barium, B ultrasound and electrocardiogram were received double balloon enteroscopy during June 2005 to June 2008. RESULTS: Thirty-six of 67 patients was done by enteroscopy via anus, and 19 cases via oral, and 12 cases via both anus and oral. The lesions were found in 41 of the 67 patients, with overall diagnostic yield of 61.19%. Among 41 cases of abdominal pain resulted from small bowel diseases, Crohn's disease were found in 15 cases (36.59%), non-specific small enteritis in 10 cases (24.39%), tumors in 8 cases (19.51%), other enteral diseases in 8 cases (19.51%). CONCLUSIONS: Double balloon enteroscopy was a diagnostic modality with a high diagnostic value for obscure abdominal pain resulted from small bowel diseases. The most common causes of obscure abdominal pain were Crohn's disease, non-specific small enteritis and tumors.

CUEDC2: multifunctional roles in carcinogenesis.

The ubiquitously expressed multifunctional protein, CUEDC2 (CUE domain-containing 2), is involved in many physiological and pathological processes, including the cell cycle regulation and inflammation. Although it is known that CUEDC2 is expressed disparately in breast cancer, ovarian carcinoma, hepatocellular carcinoma, cholangiocarcinoma, glioma, lung adenocarcinoma, colon cancers, and is involved in the Warburg's effect, its role in oncogenesis remains to be further explored. In this review, we examine the expression of CUEDC2 in various tumors, and discuss several fundamental signaling pathways that are impacted by CUEDC2.

Weekday of Surgery Affects Postoperative Complications and Long-Term Survival of Chinese Gastric Cancer Patients after Curative Gastrectomy.

Many factors have been reported to affect the long-term survival of gastric carcinoma patients after gastrectomy; the present study took the first attempt to find out the potential role of weekday carried out surgery in the postoperative prognosis of gastric cancer patients. 463 gastric cancer patients have been followed up successfully. Pearson χ2 test was used for univariate analyses. Survival curves were constructed by using Kaplan-Meier method and evaluated by using the log-rank test. The Cox proportional hazard regression model was used to find out the risk factors, and subgroup analysis was conducted to rule out confounding factors. We found that the patients who underwent gastrectomy on the later weekday (Wednesday-Friday) more easily suffered from a higher postoperative morbidity. Weekday of surgery was one of the independent indicators for the prognosis of patients after gastric cancer surgery. However, the role of weekday of surgery was significantly weakened in the complications group. In conclusion, surgery performed in the later weekday was more likely to lead to increased postoperative complications and an unfavorable role in prognosis of Chinese gastric cancer patients after curative gastrectomy.

Expression and clinical significance of Apollon in esophageal squamous cell carcinoma.

Apollon, an unusually large member of the inhibitors of apoptosis protein family, may be important for oncogenesis development. The aim of the present study was to assess the association between esophageal squamous cell carcinoma (ESCC) and Apollon expression levels, and to highlight the association between Apollon and the occurrence, development and prognosis of ESCC. Apollon expression was detected by immunohistochemical staining and reverse transcription-quantitative polymerase chain reaction in ESCC tissues, adjacent non­cancerous tissues and paired normal tissues respectively, in order to analyze the association between Apollon expression and the clinicopathological features of ESCC. Survival analysis was used to assess the prognostic significance of Apollon expression. It was determined that the mRNA and protein expression levels of Apollon were significantly higher in the carcinoma tissues compared with the adjacent non­cancerous tissues and normal control tissues (P<0.001). There was a significant difference in lymph node involvement and the tumor, nodes, and metastases stage in patients categorized according to different Apollon expression levels. The prognostic significance of Apollon was also determined using the log­rank method. The overexpression of Apollon was associated with shorter overall survival and disease-free survival rates. The present study indicates that Apollon expression is associated with the biological characteristics of ESCC, and may be a valuable prognostic factor and a novel chemotherapeutic target for ESCC treatment.

eIF4E promotes tumorigenesis and modulates chemosensitivity to cisplatin in esophageal squamous cell carcinoma.

Patients with esophageal squamous cell cancer are often diagnosed with advanced diseases that respond poorly to chemotherapy. Overexpression of eIF4E leads to enhance the translation of key malignancy-related proteins and enabling tumor growth and chemoresistance in a variety of human malignancies, but whether it has a role in ESCC remains obscure. We hypothesized that eIF4E promoted ESCC tumorigenesis and facilitated the development of acquired resistance to the cisplatin-based chemotherapy. In this study, we showed that eIF4E expression was increased significantly in clinical ESCC tissues and and ESCC cell lines and its expression level was correlated with lymph node metastasis, TNM stage, as well as overall and disease-free survival of ESCC. We also showed here that knockdown of eIF4E in EC9706 would dramatically reduced cell proliferation, colony formation, migration and invasion, apoptosis in vitro as well as in vivo, and vice versa. Moreover, "weak mRNAs" were demonstrated to be regulated by eIF4E in ESCC, which might interpret the above function. Overexpression of eIF4E decreased the efficacy of cisplatin-induced cell growth inhibition in ESCC cell line and xenograft model (P < 0.05). eIF4E knockdown by shRNA increased cisplatin-induced cytotoxicity in ESCC cell lines, and enhanced chemosensitivity to cisplatin in xenograft tumor models. Furthermore, we found that the PI3K/AKT pathway and Bcl-2/Bax ratio might be responsible for the eIF4E-induced cisplatin resistance in ESCC. Our data collectively show association of eIF4E expression with chemotherapeutic response in ESCC, and suggest that therapeutically targeting eIF4E may be a viable means of improving chemotherapy response in ESCC.

Tumor-specific expression of shVEGF and suicide gene as a novel strategy for esophageal cancer therapy.

AIM: To develop a potent and safe gene therapy for esophageal cancer. METHODS: An expression vector carrying fusion suicide gene (yCDglyTK) and shRNA against vascular endothelial growth factor (VEGF) was constructed and delivered into EC9706 esophageal cancer cells by calcium phosphate nanoparticles (CPNP). To achieve tumor selectivity, expression of the fusion suicide gene was driven by a tumor-specific human telomerase reverse transcriptase (hTERT) promoter. The biologic properties and therapeutic efficiency of the vector, in the presence of prodrug 5-fluorocytosine (5-FC), were evaluated in vitro and in vivo. RESULTS: Both in vitro and in vivo testing showed that the expression vector was efficiently introduced by CPNP into tumor cells, leading to cellular expression of yCDglyTK and decreased VEGF level. With exposure to 5-FC, it exhibited strong anti-tumor effects against esophageal cancer. Combination of VEGF shRNA with the fusion suicide gene demonstrated strong anti-tumor activity. CONCLUSION: The shVEGF-hTERT-yCDglyTK/5-FC system provided a novel approach for esophageal cancer-targeted gene therapy.