TATA-box-binding protein-associated factor 15 is a novel biomarker that promotes cell proliferation and migration in gastrointestinal stromal tumor

BACKGROUND Gastrointestinal stromal tumor(GIST)is a common neoplasm with high rates of recurrence and metastasis,and its therapeutic efficacy is still not ideal.There is an unmet need to find new molecular therapeutic targets for GIST.TATA-boxbinding protein-associated factor 15(TAF15)contributes to the progress of various tumors,while the role and molecular mechanism of TAF15 in GIST progression are still unknown.AIM To explore new molecular therapeutic targets for GIST and understand the biological role and underlying mechanisms of TAF15 in GIST progression.METHODS Proteomic analysis was performed to explore the differentially expressed proteins in GIST.Western blotting and immunohistochemical analysis were used to verify the expression level of TAF15 in GIST tissues and cell lines.Cell counting kit-8,colony formation,wound-healing and transwell assay were executed to detect the ability of TAF15 on cell proliferation,migration and invasion.A xenograft mouse model was applied to explore the role of TAF15 in the progression of GIST.Western blotting was used to detect the phosphorylation level and total level of RAF1,MEK and ERK1/2.RESULTS A total of 1669 proteins were identified as differentially expressed proteins with 762 upregulated and 907 downregulated in GIST.TAF15 was selected for the further study because of its important role in cell proliferation and migration.TAF15 was significantly over expressed in GIST tissues and cell lines.Overexpression of TAF15 was associated with larger tumor size and higher risk stage of GIST.TAF15 knockdown significantly inhibited the cell proliferation and migration of GIST in vitro and suppressed tumor growth in vivo.Moreover,the inhibition of TAF15 expression significantly decreased the phosphorylation level of RAF1,MEK and ERK1/2 in GIST cells and xenograft tissues,while the total RAF1,MEK and ERK1/2 had no significant change.CONCLUSION TAF15 is over expressed in GIST tissues and cell lines.Overexpression of TAF15 was associated with a poor prognosis of GIST patients.TAF15 promotes cell proliferation and migration in GIST via the activation of the RAF1/MEK/ERK signaling pathway.Thus,TAF15 is expected to be a novel latent molecular biomarker or therapeutic target of GIST.

Endoscopic therapy for gastric stromal tumors originating from the muscularis propria

AIM:To explore endoscopic therapy methods for gastric stromal tumors originating from the muscularis propria.METHODS:For 69 cases diagnosed as gastric stromal tumors originating from the muscularis propria,three types of endoscopic therapy were selected,based on the size of the tumor.These methods included endoscopic ligation and resection(ELR),endoscopic submucosal excavation(ESE) and endoscopic full-thickness resection(EFR).The wound surface and the perforation of the gastric wall were closed with metal clips.Immunohistostaining for CD34,CD117,Dog-1,S-100 and smooth muscle actin(SMA) was performed on the resected tumors.RESULTS:A total of 38 cases in which the tumor size was less than 1.2 cm were treated with ELR;three cases were complicated by perforation,and the perforations were closed with metal clips.Additionally,18 cases in which the tumor size was more than 1.5 cm were treated with ESE,and no perforation occurred.Finally,13 cases in which the tumor size was more than 2.0 cm were treated with EFR;all of the cases were complicated by artificial perforation,and all of the perforations were closed with metal clips.All of the 69 cases recovered with medical treatment,and none required surgical operation.Immunohistostaining demonstrated that among all of the 69 gastric stromal tumors diagnosed by gastroscopy,12 cases were gastric leiomyomas(SMA-positive),and the other 57 cases were gastric stromal tumors.CONCLUSION:Gastric stromal tumors originating from the muscularis propria can be treated successfully with endoscopic techniques,which could replace certain surgical operations and should be considered for further application.

Endoscopic full-thickness resection for gastric submucosal tumors arising from the muscularis propria layer

AIM:To evaluate the efficacy,safety and feasibility of endoscopic full-thickness resection(EFR) for the treatment of gastric submucosal tumors(SMTs) arising from the muscularis propria.METHODS:A total of 35 gastric SMTs arising from the muscularis propria layer were resected by EFR between January 2010 and September 2013.EFR consists of five major steps:injecting normal saline into the submucosa;pre-cutting the mucosal and submucosal layers around the lesion;making a circumferential incision as deep as the muscularis propria around the lesion using endoscopic submucosal dissection and an incision into the serosal layer around the lesion with a Hook knife;a full-thickness resection of the tumor,including the serosal layer with a Hook or IT knife;and closing the gastric wall with metallic clips.RESULTS:Of the 35 gastric SMTs,14 were located at the fundus,and 21 at the corpus.EFR removed all of the SMTs successfully,and the complete resection rate was 100%.The mean operation time was 90 min(60-155 min),the mean hospitalization time was 6.0 d(4-10 d),and the mean tumor size was 2.8 cm(2.0-4.5cm).Pathological examination confirmed the presence of gastric stromal tumors in 25 patients,leiomyomas in7 and gastric autonomous nerve tumors in 2.No gastric bleeding,peritonitis or abdominal abscess occurred after EFR.Postoperative contrast roentgenography on the third day detected no contrast extravasation into the abdominal cavity.The mean follow-up period was 6mo,with no lesion residue or recurrence noted.CONCLUSION:EFR is efficacious,safe and minimally invasive for patients with gastric SMTs arising from the muscularis propria layer.This technique is able to resect deep gastric lesions while providing precise pathological information about the lesion.With the development of EFR,the indications of endoscopic resection might be extended.

Endoscopic mucosal resection for rectal carcinoids under micro-probe ultrasound guidance

AIM: To assess the therapeutic value of endoscopic mucosal resection (EMR) under micro-probe ultrasound guidance for rectal carcinoids less than 1 cm in diameter. METHODS: Twenty-one patients pathologically diagnosed with rectal carcinoids following colonoscopy in our hospital from January 2007 to November 2012 were included in this study. The patients consisted of 14 men and 7 women, with a mean age of 52.3 ± 12.2 years (range: 36-72 years). The patients with submucosal tumors less than 1 cm in diameter arising from the rectal and muscularis mucosa detected by micro-probe ultrasound were treated with EMR and followed up with conventional endoscopy and micro-probe ultrasound. RESULTS: All of the 21 tumors were confirmed by micro-probe ultrasound as uniform hypoechoic masses originating from the rectal and muscularis mucosa, without invasion of muscularis propria and vessels, and less than 1 cm in diameter. EMR was successfully completed without bleeding, perforation or other complications. The resected specimens were immunohistochemically confirmed to be carcinoids. Patients were followed up for one to two years, and no tumor recurrence was reported. CONCLUSION: EMR is a safe and effective treatment for rectal carcinoids less than 1 cm in diameter.

Endoscopic full-thickness resection and laparoscopic surgery for treatment of gastric stromal tumors

AIM: To assess the effectiveness of endoscopic fullthickness resection(EFR) and laparoscopic surgery in the treatment of gastric stromal tumors arising from the muscularis propria.METHODS: Out of 62 gastric stromal tumors arising from the muscularis propria, each > 1.5 cm in diameter, 32 were removed by EFR, and 30 were removed by laparoscopic surgery. The tumor expression of CD34, CD117, Dog-1, S-100, and SMA was assessed immunohistochemically. The operative time, complete resection rate, length of hospital stay, incidence of complications, and recurrence rate were compared between the two groups. Continuous data were compared using in-dependent samples t-tests, and categorical data were compared using χ2 tests.RESULTS: The 32 gastric stromal tumors treated by EFR and the 30 treated by laparoscopic surgery showed similar operative time [20-155 min(mean, 78.5 ± 30.1 min) vs 50-120 min(mean, 80.9 ± 46.7 min), P > 0.05], complete resection rate(100% vs 93.3%, P > 0.05), and length of hospital stay [4-10 d(mean, 5.9 ± 1.4 d) vs 4-19 d(mean, 8.9 ± 3.2 d), P >0.05]. None of the patients treated by EFR experienced complications, whereas two patients treated by laparoscopy required a conversion to laparotomy, and one patient had postoperative gastroparesis. No recurrences were observed in either group. Immunohistochemical staining showed that of the 62 gastric stromal tumors diagnosed by gastroscopy and endoscopic ultrasound, six were leiomyomas(SMA-positive), one was a schwannoglioma(S-100 positive), and the remaining 55 were stromal tumors.CONCLUSION: Some gastric stromal tumors arising from the muscularis propria can be completely removed by EFR. EFR could likely replace surgical or laparoscopic procedures for the removal of gastric stromal tumors.

Meckel's diverticulum bleeding diagnosed with magnetic resonance enterography:A case report

Although the introduction of double-balloon enteroscopy has greatly improved the diagnostic rate, definite diagnosis of Meckel's diverticulum far from the ileocecal valve is still impossible in most cases. We explored the role of magnetic resonance (MR) enterography in detecting bleeding from Meckel's diverticulum that can not be confirmed via double-balloon enteroscopy. This study describes a case of male patient with bleeding from Meckel's diverticulum diagnosed with MR enterography of the small intestine. No bleeding lesion was found via colonoscopy, anal enteroscopy, or oral colonoscopy. MR enterography of the small intestine revealed an occupying lesion of 3.0 cm in the lower segment of the ileum. The patient was transferred to the Department of Abdominal Surgery of our hospital for surgical treatment. During surgery, a mass of 3 cm × 2 cm was found 150 cm from the ileocecal valve, in conjunction with congestion and edema of the corresponding mesangium. Intraoperative diagnosis was small bowel diverticulum with bleeding. The patient underwent partial resection of the small intestine. Postopera-tive pathology showed Meckel's diverticulum containing pancreatic tissues. He was cured and discharged 7 d after operation. We conclude that MR enterography of the small intestine has greatly improved the diagnosis rate of Meckel's diverticulum, particularly in those patients with the disease which can not be confirmed via double-balloon enteroscopy.

Small intestinal vascular malformation bleeding:A case report with imaging findings

The small intestine is approximately 5-6 m long and occupies a large area in the abdominal cavity. These factors preclude the use of ordinary endoscopy and X-ray to thoroughly examine the small intestine for bleeding of vascular malformations. Thus,the diagnosis of intestinal bleeding is very difficult. A 47-year-old man presented at the hospital 5 mo ago with dark stool. Several angiomas were detected by oral approach enteroscopy,but no active bleeding was observed. Additionally,no lesions were detected by anal approach enteroscopy;however,gastrointestinal tract bleeding still occurred for an unknown reason. We performed an abdominal vascular enhanced computed tomography examination and detected ileal vascular malformations. Ileum angioma and vascular malformation were detected by a laparoscopic approach,and segmental resection was performed for both lesions,which were confirmed by pathological diagnosis. This report systemically emphasizes the imaging findings of small intestinal vascular malformation bleeding.

Activated rat hepatic stellate cells influence Th1/Th2 profile in vitro

AIM: To investigate the effects of activated rat hepatic stellate cells(HSCs) on rat Th1/Th2 profile in vitro.METHODS: Growth and survival of activated HSCs and CD4+ T lymphocytes cultured alone or together was assessed after 24 or 48 h. CD4+ T lymphocytes were then cultured with or without activated HSCs for 24 or 48 h and the proportion of Th1 [interferon(IFN)-γ+] and Th2 [interleukin(IL)-4+] cells was assessed by flow cytometry. Th1 and Th2 cell apoptosis was assessed after 24 h of co-culture using a caspase-3 staining procedure. Differentiation rates of Th1 and Th2 cells from CD4+ T lymphocytes that were positive for CD25 but did not express IFN-γ or IL-4 were also assessed after 48 h of co-culture with activated HSCs. Galectin-9 expression in HSCs was determined by immunofluorescence and Western blotting. ELISA was performed to assess galectin-9 secretion from activated HSCs.RESULTS: Co-culture of CD4+ T lymphocytes with activated rat HSCs for 48 h significantly reduced the proportion of Th1 cells compared to culture-alone conditions(-1.73% ± 0.71%; P < 0.05), whereas the proportion of Th2 cells was not altered; the Th1/Th2 ratio was significantly decreased(-0.44 ± 0.13; P < 0.05). In addition, the level of IFN-γ in Th1 cells wasdecreased(-65.71 ± 9.67; P < 0.01), whereas the level of IL-4 in Th2 cells was increased(82.79 ± 25.12; P < 0.05) by co-culturing, as measured by mean fluorescence intensity by flow cytometry. Apoptosis rates in Th1(12.27% ± 0.99%; P < 0.01) and Th2(1.71% ± 0.185%; P < 0.01) cells were increased 24 h after co-culturing with activated HSCs; the Th1 cell apoptosis rate was significantly higher than in Th2 cells(P < 0.01). Galectin-9 protein expression was significantly decreased in HSCs only 24 h after coculturing(P < 0.05) but not after 48 h. Co-culture for 48 h significantly increased the differentiation of Th1 and Th2 cells; however, the increase in the proportion of Th2 cells was significantly higher than that of Th1 cells(1.85% ± 0.48%; P < 0.05).CONCLUSION: Activated rat HSCs lower the Th1/Th2 profile, inhibiting the Th1 response and enhancing the Th2 response, and this may be a novel pathway for liver fibrogenesis.

Clinical Control Study of Endoscopic Full-thickness Resection and Laparoscopic Surgery in the Treatment of Gastric Tumors Arising from the Muscularis Propria

Background： Gastric stromal tumors arising from the muscularis propria are located in deeper layers. Endoscopic resection may be contraindicated due to the possibility of perforation. These tumors are therefore usually removed by surgical or laparoscopic procedures. This study evaluated the curative effects, safety and feasibility of endoscopic full-thickness resection （EFR） of gastric stromal tumors originating from the muscularis propria. Methods： This study enrolled 92 patients with gastric stromal tumors 〉2.5 cm originating from the muscularis propria. Fifty patients underwent EFR, and 42 underwent laparoscopic intragastric surgery. Operation time, complete resection rate, length of hospital stay, incidence of complications, and recurrence rates were compared in these two groups. Results： EFR resulted in complete resection of all 50 gastric stromal tumors, with a mean procedure time of 85± 20 min, a mean hospitalization time of 7.0± 1.5 days and no complications. Laparoscopic intragastric surgery also resulted in a 100% complete resection rate, with a mean operation time of 88 ± 12 min and a mean hospitalization period of 7.5 ± 1.6 days. The two groups did not differ significantly in operation time, complete resection rates, hospital stay or incidence of complications （P 〉 0.05）. No patient in either group experienced tumor recurrence. Conclusions： EFR technique is effective and safe for the resection of gastric stromal tumors arising from the muscularis propria.

Effect of Double-Balloon Enteroscopy on Diagnosis and Treatment of Small-Bowel Diseases

Background： The diagnosis and treatment of small-bowel diseases is clinically difficult. The purpose of this study was to evaluate the diagnostic and therapeutic value of double-balloon enteroscopy in small-bowel diseases. Methods： The history and outcomes of 2806 patients who underwent double-balloon enteroscopy from July 2004 to April 2017 were reviewed, which included 562 patients with obscure digestive tract bleeding, 457 patients with obscure diarrhea, 930 patients with obscure abdominal pain, 795 patients with obscure weight loss, and 62 patients with obscure intestinal obstruction. Examinations were performed through the mouth and/or anus according to the clinical symptoms and abdominal images, lfa lesion was not detected through one direction, examination through the other direction was performed as necessary. Eighty-four patients with small-bowel polyps, 26 with intestinal obstruction caused by enterolith, and 18 with bleeding from Dieulafoy＇s lesions in the small intestine were treated endoscopically. Results： A total of 2806 patients underwent double-balloon enteroscopy, and no serious complications occurred. An endoscopic approach through both the mouth and anus was used in 212 patients. Lesions were detected in 1696 patients, with a detection rate of 60.4%： the rates for obscure digestive tract bleeding, diarrhea, abdominal pain, weight loss, and intestinal obstrtlction were 85.9% （483/562）, 73.5% （336/457）, 48.2% （448/930）, 49.1% （390/795）, and 62.9% （39/62）, respectively. For patients with small-bowel polyps who underwent endoscopic therapy, no complications such as digestive tract bleeding and perforation occurred. Intestinal obstruction with enteroliths was relieved with endoscopic lithotripsy. Among the 18 patients with bleeding from small-bowel Dieulafoy＇s lesions, 14 patients were controlled with endoscopic hemostasis. Conclusion： Double-balloon enteroscopy is useful for diagnosing and treating some small-bowel disease.

Screening for Differentially Expressed Genes of Gastric Stromal Tumor Originating from Muscularis Propria

INTRODUCTION Gastric stromal tumor （GST） is a set of gastrointestinal mesenchymal tumors those originate from interstitial cells of Cajal. Its early diagnosis and treatment are critical to prognosis. The occurrence of GST remains obscure; this study used Affymetrix expression spectrum chip to detect the gene expression spectrum of GST and explore new molecular target that is used in the treatment and prognosis of GST.