[Show abstract][Hide abstract] ABSTRACT: Gastric dysplasia is a well-known precancerous lesion. Though the diagnosis of gastric low grade dysplasia (LGD) is generally made from endoscopic forceps biopsy (EFB), the accuracy is doubtful after numerous EFB-proven gastric LGD were upgraded to gastric high grade dysplasia (HGD) or even carcinoma (CA) by further diagnostic test with the procedure of endoscopic resection (ER). We aimed to evaluate the upgraded diagnosis rate (UDR) and the risk factors by ER in EFB-proven gastric LGD lesions. Two investigators independently searched studies reporting the UDR by ER in EFB-proven gastric LGD lesions from databases and analyzed the overall UDR, HGD-UDR and CA-UDR. The pooled UDR by ER in EFB-proven gastric LGD lesions was 25.0% (95% CI, 20.2%-29.8%), made up of HGD-UDR and CA-UDR by rates of 16.7% (95% CI, 12.8%-20.6%) and 6.9% (95% CI, 4.2%-9.6%) respectively. Lesion size larger than 2 cm, surface with depression and nodularity under endoscopic examinations were the major risk factors associated with UDR. In conclusion, one quarter of EFB-proven gastric LGD lesions will be diagnosed as advanced lesions, including gastric HGD (16.7%) and gastric CA (6.9%) by ER. The diagnosis of those LGD lesions with an endoscopic diameter larger than 2cm, and depressed or nodular surface are more likely to be upgraded after ER.
PLoS ONE 07/2015; 10(7):e0132699. DOI:10.1371/journal.pone.0132699 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Endoscopic tattoo with India ink injection for surveillance of premalignant gastric lesions is technically cumbersome and may not be durable. The aim of the study is to evaluate the accuracy of a novel, computer-simulated biopsy marking system (CSBMS) developed for the endoscopic marking of gastric lesions. Twenty-five patients with history of gastric intestinal metaplasia received both CSBMS-guided marking and India ink injection in five points in the stomach at index endoscopy. A second endoscopy was performed at three months. Primary outcome was accuracy of CSBMS (distance between CSBMS probe-guided site and tattoo site measured by CSBMS). The mean accuracy of CSBMS at angularis was 5.3 ± 2.2 mm, antral lesser curvature 5.7 ± 1.4 mm, antral greater curvature 6.1 ± 1.1 mm, antral anterior wall 6.9 ± 1.6 mm, and antral posterior wall 6.9 ± 1.6 mm. CSBMS (2.3 ± 0.9 versus 12.5 ± 4.6 seconds; P = 0.02) required less procedure time compared to endoscopic tattooing. No adverse events were encountered. CSBMS accurately identified previously marked gastric sites by endoscopic tattooing within 1 cm on follow-up endoscopy.
[Show abstract][Hide abstract] ABSTRACT: Background
Patients frequently consult primary care physicians and gastroenterologists when experiencing chronic abdominal pain. Although its diagnostic efficacy in these settings is uncertain, small-bowel capsule endoscopy (SBCE) has been used to evaluate the unexplained reasons for abdominal pain.
To evaluate the diagnostic yield of SBCE in patients with unexplained chronic abdominal pain.
We performed a retrospective review of publications reporting the diagnostic yield of SBCE in patients with unexplained chronic abdominal pain and calculated the overall diagnostic yield.
Two investigators independently searched studies from databases and analyzed the results.
A total of 1520 patients from 21 studies were included.
Small-bowel capsule endoscopy.
Main Outcome Measurements
Per-patient diagnostic yield, with 95% confidence intervals (CI), was evaluated by a random-effect model. Clear categorical analysis also was performed.
The pooled diagnostic yield of SBCE in patients with unexplained chronic abdominal pain was 20.9% (95% CI, 15.9%-25.9%), with high heterogeneity (I2 = 80.0%; P ＜ .001). Inflammatory lesions were the most common (78.3%) positive findings, followed by tumors (9.0%).
Heterogeneity among studies, retrospective design, variable chronicity of abdominal pain, and different previous examinations before SBCE.
SBCE provides a noninvasive diagnostic tool for patients with unexplained chronic abdominal pain, but the diagnostic yield is limited (20.9%). Among patients with positive findings, inflammatory lesions are the most common.
[Show abstract][Hide abstract] ABSTRACT: The KRAS oncogene influences angiogenesis, metastasis and chemoresistance in colorectal cancers (CRCs), and these processes are all enhanced in hypoxic conditions. To define functional activities of mutant KRAS in a hypoxic microenvironment, we first performed cDNA microarray experiments in isogenic DKs5 and DKO3 colon cancer cell lines that differ only by their expression of mutant KRAS (K-ras(D13) ). Adrenomedullin (ADM) was identified as one of the most significantly upregulated genes in DKs5 cells that express the KRAS oncogene in hypoxia (3.2-fold, p = 1.47 × 10(-5) ). Ectopic expression of mutant KRAS (K-ras(V12) ) in Caco-2 cells (K-ras(WT) ) induced ADM, whereas selective knockdown of mutant KRAS alleles (K-ras(D13) or K-ras(V12) ) in HCT116, DLD1 and SW480 colon cancer cells suppressed the expression of ADM in hypoxia. Knockdown of ADM in colon tumor xenografts blocked angiogenesis and stimulated apoptosis, resulting in tumor suppression. Furthermore, ADM also regulated colon cancer cell invasion in vitro. Among 56 patients with CRC, significantly higher expression levels of ADM were observed in samples harboring a KRAS mutation. Collectively, ADM is a new target of oncogenic KRAS in the setting of hypoxia. This observation suggests that therapeutic targets may differ depending upon the specific tumor microenvironment.
International Journal of Cancer 05/2014; 134(9):2041-50. DOI:10.1002/ijc.28542 · 5.09 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Homeobox D10 (HoxD10) plays important roles in the differentiation of embryonic cells and progression of breast cancer. Our previous report revealed that insulin-like growth factor binding protein-3 (IGFBP3) was regulated by HoxD10 in gastric cancer cells; however, the functional roles and underlying mechanisms of IGFBP3 in gastric cancer remain unclear. Here, we found that the expression of IGFBP3 were upregulated after ectopic expression of HoxD10 in gastric cancer cells. Chromatin immunoprecipitation assay showed that HoxD10 bound to three potential regions of IGFBP3 promoter. Exogenous HoxD10 significantly enhanced the activity of luciferase reporter containing these binding regions in gastric cancer cells. Further data showed that all of these binding sites had Hox binding element "TTAT". Immunohistochemical staining results revealed that IGFBP3 expression was significantly downregulated in 86 gastric adenocarcinomas tissues relative to their adjacent non-cancerous tissues (p<0.001). Moreover, IGFBP3 expression was significantly lower in gastric tumor with lymph node metastasis compared with that without lymph node metastasis (p=0.045). Patients with high expression level of IGFBP3 showed favorable 5 year overall survival (p=0.011). Knockdown of IGFBP3 accelerated gastric cancer cell migration and invasion and induced the expression of invasive factors including MMP14, uPA and uPAR. Thus, our data suggest that HoxD10-targeted gene IGFBP3 may suppress gastric cancer cell invasion and favors the survival of gastric cancer patients.
PLoS ONE 12/2013; 8(12):e81423. DOI:10.1371/journal.pone.0081423 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Growing evidence indicates that miRNAs play critical roles in tumorigenesis and cancer progression. Here, we report that miR-215 is significantly up-regulated in gastric cancer tissues from either gastrectomy or gastroscopy. Receiver Operator Characteristic (ROC) curve analysis indicated that miR-215 may be a candidate biomarker for gastric cancer diagnosis. Inhibition of miR-215 significantly suppressed gastric cancer cell proliferation possibly via G1 arrest. Further analyses indicated that miR-215 was able to target retinoblastoma tumor-suppressor gene 1 (RB1) through its 3'-UTR in gastric cancer cells. These data suggest that frequently up-regulated miR-215 in gastric cancer may influence cell proliferation by targeting RB1.
Cancer letters 08/2013; 342(1). DOI:10.1016/j.canlet.2013.08.033 · 5.62 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background
ZIC1, a vital transcription factor with zinc finger domains, has been implicated in the process of neural development. We previously showed that ZIC1 may function as a tumour suppressor in gastrointestinal cancers. However, the molecular mechanism underlying ZIC1 participation in tumour progression remains unknown.
The role of ZIC1 on cell proliferation and migration was examined. The regulation of sonic hedgehog (Shh), phosphoinositide 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) signaling pathways after ectopic expression of ZIC1 in gastric cancer cells were evaluated.
Overexpression of ZIC1 contributes to the inhibition of cell proliferation migration and cell-cycle distribution in gastric cancer. The modulation of G1/S checkpoint by ZIC1 is mainly mediated through the regulation of cyclin-dependent kinases (p21 Waf1/Cip1, p27 Kip1 and cyclin D1). In addition, ZIC1 can inactivate the level of phospholated Akt and Erk1/2, and transcriptionally regulate sonic hedgehog (Shh) signaling, thus leading to regulate the expression of p21 Waf1/Cip1 and cyclin D1. Finally, we have systemically identified ZIC1 downstream targets by cDNA microarray analysis and revealed that 132 genes are down-regulated and 66 genes are up-regulated after transfection with ZIC1 in gastric cancer cells. These candidate genes play critical roles in cell proliferation, cell cycle and cell motility.
Overexpression of ZIC1 results in inactivation of Shh, PI3K and MAPK signaling pathways, as well as regulation of multiple downstream targets which are essential for the development and progression of gastric cancer. ZIC1 serves as a potential therapeutic target for gastric cancer.
BMC Cancer 07/2012; 12(1). DOI:10.1186/1471-2407-12-290 · 3.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Homeobox D10 (HoxD10 ) gene plays a critical role in cell differentiation and morphogenesis during development. However, the function of HoxD10 in tumor progression remains largely unknown. We demonstrate that the expression of HoxD10 is commonly downregulated in gastric cancer tissues (n = 33) and cell lines (n = 8) relative to normal stomach tissues. Functionally, reexpression of HoxD10 results in significant inhibition of cell survival, induction of cell apoptosis, and impairment of cell migration and invasion. Moreover, ectopic expression of HoxD10 suppresses gastric tumor growth in a mouse xenograft model. To identify target candidates of HoxD10, we performed cDNA microarray and showed that HoxD10 regulates multiple downstream genes including IGFBP3. Reintroduction of HoxD10 transcriptionally upregulates IGFBP3, activates caspase 3 and caspase 8, and subsequently induces cell apoptosis. Methylation specific PCR revealed that HoxD10 promoter DNA was hypermethylated in gastric cancer cell lines. Additionally, 5-aza demethylation treatment could transiently reactivate the expression of HoxD10 in gastric cancer cells. HoxD10 promoter methylation frequently was detected in gastric cancer tissues obtained from endoscopic biopsies (85.7%, 24/28) and surgically resected samples (82.6%, 57/69). Intestinal metaplasia tissues showed a 60% methylation rate (18/30), but no detectable methylation in normal stomach tissues (0%, 0/10). Taken together, our results suggest that HoxD10 functions as a candidate tumor suppressor in gastric cancer, which is inactivated through promoter hypermethylation.
Molecular Medicine 12/2011; 18(1):389-400. DOI:10.2119/molmed.2011.00172 · 4.51 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The role of gastrin on the development of atrophic gastritis (AG) and its relationship with the expression of RegIα in vivo remain unclear. We established experimental AG in rats by combination administration with sodium salicylate, alcohol, and deoxycholate sodium. The mean score of inflammation in gastric antrum in AG rats was significantly elevated (P < 0.05), while the number of glands dramatically decreased (P < 0.05). In addition, the cell proliferation in gastric glands was increased in experimental AG rats, as determined by immunohistochemistry staining of PCNA and GS II. The level of serum gastrin in AG rats was significantly elevated relative to that of normal rats (P < 0.01). Moreover, the expression of RegIα protein and its receptor mRNA was increased in gastric tissues in AG rats (P < 0.05). Taken together, we demonstrated that the overexpression of Reglα is related with hypergastrinemia in AG rats.
Gastroenterology Research and Practice 09/2011; 2011(5):403956. DOI:10.1155/2011/403956 · 1.75 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The transcription factor, Zinc finger of the cerebellum (ZIC1), plays a crucial role in vertebrate development. Recently, ZIC1 has also been found to participate in the progression of human cancers, including medulloblastomas, endometrial cancers, and mesenchymal neoplasms. However, the function of ZIC1 in colon cancer progression has not been defined. In this study, we demonstrate ZIC1 to be silenced or significantly downregulated in colon cancer cell lines. These effects were reversed by demethylation treatment with 5-aza-2'-deoxycytidine (Aza). ZIC1 expression is also significantly downregulated in primary colorectal cancer tissues relative to adjacent non-tumor tissues (p = 0.0001). Furthermore, methylation of ZIC1 gene promoter is frequently detected in primary tumor tissues (85%, 34/40), but not in adjacent non-tumor tissues. Ectopic expression of ZIC1 suppresses cell proliferation and induces apoptosis, which is associated with MAPK and PI(3)K/Akt pathways, as well as the Bcl-xl/Bad/Caspase3 cascade. To identify target candidates of ZIC1, we employed cDNA microarray and found that 337 genes are downregulated and 95 genes upregulated by ectopic expression of ZIC1, which were verified by 10 selected gene expressions by qRT-PCR. Taken together, our results suggest that ZIC1 may potentially function as a tumor suppressor gene, which is downregulated through promoter hypermethylation in colorectal cancers.
PLoS ONE 02/2011; 6(2):e16916. DOI:10.1371/journal.pone.0016916 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: As one of major epigenetic changes to inactivate tumor suppressor genes in human carcinogenesis, promoter hypermethylation was proposed as a marker to define novel tumor suppressor genes and predict the prognosis of cancer patients. In the present study, we found KL (klotho) as a novel tumor suppressor gene silenced through promoter hypermethylation in gastric cancer, the second leading cause of cancer death worldwide. KL expression was downregulated in primary gastric carcinoma tissues (n=22, p<0.05) and all of gastric cancer cells lines examined. Ectopic expression of KL inhibited the growth of gastric cancer cells partially through the induction of apoptosis, demonstrating a tumor suppressive role of KL in gastric cancer. Demethylation with 5-aza-2'-deoxycytidine (Aza) increased KL expression and KL promoter was hypermethylated in gastric cancer cell lines as well as some of primary gastric carcinoma tissues (47/99) but none of normal gastric tissues. Importantly, promoter methylation of KL was significantly associated with the poor outcome of gastric cancer patients (p=0.025, Log-rank test), highlighting the relevance of epigenetic inactivation of KL in gastric carcinogenesis. As a summary, we found that KL is a novel tumor suppressor gene epigenetically inactivated in gastric cancer and promoter methylation of KL could be used to predict the prognosis of gastric cancer patients.
American Journal of Cancer Research 01/2011; 1(1):111-119. · 4.17 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Gastric carcinogenesis is a multiple-stage process. It is believed that a premalignant lesion often precedes or accompanies gastric cancer, although the underlying mechanisms have not been fully elucidated. Here, we revealed that REG Iα was frequently overexpressed not only in gastric cancer tissues, but also in the intestinal metaplastic and atypical dysplasia gland, which are considered precancerous lesions, in 102 patients. To investigate the role of REG Iα in gastric cancer, we employed siRNA-mediated silencing techniques and found that the downregulation of REG Iα significantly inhibited gastric cancer cell proliferation, whereas overexpression of REG Iα promoted proliferation. In addition, REG Iα appeared to have an anti-apoptotic effect in gastric cancer cells, which was associated with the Bad/Bcl-xL/caspase-3 pathway. Furthermore, gastrin was found to activate REG Iα expression and nuclear translocation of β-catenin in gastric cancer cells. Thus, these data suggest that REG Iα, a potential downstream of gastrin, may be involved in gastric carcinogenesis.
Molecular Medicine Reports 11/2010; 3(6):999-1005. DOI:10.3892/mmr.2010.364 · 1.55 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Lack of clinical biomarkers for early gastric cancer without specific early symptoms leads to delayed diagnosis, which contributes to high mortality of gastric cancer. Here, we used oligonucleotide microarray to systematically examine differential gene expression among 33 samples from normal, premalignant, and malignant lesions in stomach. A focal adhesion pathway mainly composed of collagen genes was found to have a significantly different expression profile in gastric cancers compared to premalignant lesions. A subset of collagen genes efficiently separated malignant from premalignant tissues, and two representative genes COL11A1 and COL1A1 were validated in 42 tissue samples with quantitative reverse transcription-PCR and in situ hybridization. The data above suggest that focal adhesion pathway may have a role in the pathogenesis of gastric cancer, and the expression profile of collagen genes may be a potential biomarker to distinguish malignant from premalignant lesions in stomach.
The Anatomical Record Advances in Integrative Anatomy and Evolutionary Biology 05/2009; 292(5):692-700. DOI:10.1002/ar.20874 · 1.54 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background
Upper gastrointestinal bleeding with complicated factors is always difficult to find the primary origin.
Here we present a case of a 74-year-old male farmer suffered from acute upper gastrointestinal bleeding caused by gastric ulcer and Mallory-Weiss syndrome and chronic anemia which was at last found caused by hook worm infection.
It tells us that considering multi-possibility when can not explain the symptom with monophyletism is very important for clinicians.
[Show abstract][Hide abstract] ABSTRACT: Mucosa marking targeting biopsy (MTB) technique has been tested and verified in animal model. For multi-focal atrophic gastritis, random biopsy may miss the point of atrophy, intestinal metaplasia or dysplasia. In order to monitor chronic atrophic gastritis on gastroscopy, get the proper biopsy sample is very important.
Fifty-three atrophic gastritis patients were enrolled prospectively in this study. India ink was tattooed at five points of stomach. Endoscopy was repeated at 3, 9, 15 and 24 months.
Tattoos (96.2%) produced with 1:10 concertrations were visible with a good to excellent tattoo persistence at 3 months. Only two patients (3.8%) had poor tattoo persistence and were retattooed at 3-months interval. Tattoos did not disappear in patients who repeated for more than two gastroscopies at 24 months or even long. There were no complications related to India ink tattooing including abdominal pain, bleeding or perforation. At follow-up gastroscopy, no ulcers, inflammation, break in the mucosa, or pain was noted.
Clinical use of MTB technique is safe and persistence and may be used as an effective method for longitudinal follow-up in atrophic gastritis and other precancerous lesions.