[Retracted] Downregulation of miR­29b targets DNMT3b to suppress cellular apoptosis and enhance proliferation in pancreatic cancer.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that certain of the Hoechst staining data shown in Fig. 4E were strikingly similar to data appearing in different form in another article by different authors at a different research institute; moreover, an unexpectedly high degree of similarity was noted with the data featured in a couple of different data panels showing the results of apoptosis experiments in Fig. 4D. Owing to the fact that the contentious data in the above article had already been published prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 17: 2113­2120, 2018; DOI: 10.3892/mmr.2017.8145].

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-box-binding 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.

TAF15 promotes cell proliferation, migration and invasion of gastric cancer via activation of the RAF1/MEK/ERK signalling pathway.

TATA-box-binding protein-associated Factor 15 (TAF15), a member of the FUS/EWS/TAF15 (FET) family, contributes to the progression of various tumours. However, the role and molecular mechanism of TAF15 in gastric cancer (GC) progression are still unknown. In this study, we found that TAF15 was significantly upregulated in GC tumour tissues and cell lines. Overexpression of TAF15 was associated with a larger tumour size, high pathologic stage and high T stage of GC. TAF15 knockdown suppressed the proliferation, migration and invasion of GC cells in vitro and inhibited the tumour growth in vivo. Additionally, TAF15 knockdown led to the significant reductions in the phosphorylation levels of RAF1, MEK and ERK1/2, while total RAF1, MEK and ERK1/2 exhibited no significant change in GC cell lines. In summary, TAF15 is overexpressed in GC tumour tissues and cell lines, and promotes cell proliferation, migration and invasion in GC via the RAF1/MEK/ERK signaling pathway, which suggests that TAF15 might be a potential molecular diagnostic marker or therapeutic target for GC.

Temporal Trends and Projection of Cancer Attributable to Human Papillomavirus Infection in China, 2007-2030.

BACKGROUND: Information on temporal trends of cancer attributable to human papillomavirus (HPV) in China is limited. METHODS: Cancer incidence and mortality during 2007 to 2015 were extracted from the Chinese Cancer Registry Annual Report and the national population from the National Bureau of Statistics. HPV-attributable cancer burden and the average annual percentage change during 2007 to 2015 were estimated and cancer burden during 2016 to 2030 was projected. RESULTS: HPV-attributable cancer cases have increased by 3.8% [95% confidence interval (CI), 2.9%-4.8%] annually from 85,125 to 113,558 and age-standardized incidence rate (ASIR) rose by 3.0% (95% CI, 2.5%-3.5%) from 4.67 to 5.83 per 100,000 persons during 2007 to 2015. Cervical, female anal, and vulva cancer cases have increased by 3.8% (95% CI, 2.8%-4.7%), 6.5% (95% CI, 1.2%-12.2%), and 3.7% (95% CI, 1.6%-5.8%) per year. Male anal and oropharyngeal cancer cases have elevated by 7.5% (95% CI, 2.8%-12.5%) and 4.4% (95% CI, 2.4%-6.3%) annually. The increases of cervical and anal cancer were most rapid among those aged 50 and older. HPV-attributable cancer deaths and mortality rate have risen by 4.7% (95% CI, 2.9%-6.7%) and 3.3% (95% CI, 0.9%-5.8%) respectively. HPV-attributable cancer cases and ASIR are projected to reach 214,077 and 9.35 of 100,000 persons by 2030 respectively, with 87.7% being cervical cancer, and anal cancer cases are expected to triple. CONCLUSIONS: HPV-attributable cancer burden has largely increased in the past and will keep rising for the next decade. Cervical cancer control should be the priority and anal cancer prevention should be addressed. IMPACT: This study supplies fundamental evidence for policy-making on HPV-attributable cancer control.

Cervical cancer burden, status of implementation and challenges of cervical cancer screening in Association of Southeast Asian Nations (ASEAN) countries.

Multiple barriers impede the transformation of evidence-based research into implementation of cervical cancer screening in ASEAN countries. This review is the first of its kind to show the disease burden of cervical cancer, progress till date to implement screening and corresponding challenges, and propose tailored solutions to promote cervical cancer prevention in ASEAN. In 2020, approximately 69 000 cervical cancer cases and 38 000 deaths happened in ASEAN, and more than 44% and 63% increases on new cases and deaths are expected in 2040. Only four countries have initiated population-based cervical cancer screening programs, but the participation rate is less than 50% in some countries and even lower than 10% in Myanmar and Indonesia. Inequity and unavailability in service delivery, lack of knowledge and awareness, limited follow-up and treatment capacity, and funding sustainability affect successful scale-up of cervical cancer screening most in ASEAN. Implementing HPV detection-based primary screening, appropriate management of screen-positives, enhancing health education, integrating health services can accelerate reduction of cervical cancer burden in ASEAN. Achieving high screening coverage and high treatment compliance will help ASEAN countries remain aligned to cervical cancer elimination strategies.

Risk assessment of self-sampling HPV tests based on PCR, signal amplification to guide the appropriate screening intervals: A prospective study in China.

Objective: We assessed the longitudinal risk of developing cervical intraepithelial neoplasia (CINs) with self-sampling human papillomavirus (HPV) tests, based on polymerase chain reaction (PCR) and signal amplification (careHPV), to explore the appropriate intervals for cervical cancer screening. Methods: A prospective study was conducted in China during 2017-2020. Participants were invited for PCR and careHPV tests with self-samples at baseline. Women positive in either HPV test underwent colposcopy and biopsy if necessary. Women with baseline CIN grade one (CIN1) or less were followed up over 3 years. The absolute risk was assessed by the immediate risk (IR) and cumulative risk (CR), and the relative risk was assessed by the hazard ratio (HR) with a 95% confidence interval (CI). Results: A total of 8,126 women were included in the final analysis. Women positive for the PCR HPV test had comparable IRs of CIN2+ and CIN3+ to those positive on the careHPV test. With triage by HPV genotyping, women with HPV 16/18 infection had the highest IRs of CIN2+ (21.15%) and CIN3+ (9.67%). For CR, women negative for PCR HPV test had a lower risk of CIN2+ than that reported in women negative on careHPV test (0.57% versus 0.98%, HR = 0.58, 95% CI: 0.38, 0.87), but no significant difference was found in the CRs of CIN3+ between them (0.25% versus 0.39%, HR = 0.64, 95% CI: 0.34, 1.20). Among women with CIN1 or less at baseline, women who were persistent or recurrent positive on careHPV or PCR HPV test had a higher risk of developing CIN3+ (11.36%-14.59%), compared with women remained HPV negative from baseline throughout follow-up (≤0.28%). Conclusions: Routine screening with 3-year intervals is acceptable for self-sampling HPV tests based on PCR or careHPV test. Women positive on HPV16/18 triaging at baseline or with CIN1 or less at baseline while being persistent or recurrent positive on careHPV or PCR HPV test during 3-year follow-up require immediate colposcopy or treatment.

Centromere Protein I (CENP-I) Is Upregulated in Gastric Cancer, Predicts Poor Prognosis, and Promotes Tumor Cell Proliferation and Migration.

This study aimed to investigate the expression and cellular function of the centromeric family of proteins (CENPs), especially centromere protein I (CENP-I), in gastric cancer (GC) and identified its clinical significance and cellular functions. CENP-I expression in GC was studied by cDNA microarray, quantitative real-time PCR (qRT-PCR), and immunohistochemistry (IHC), and using datasets from The Cancer Genome Atlas (TCGA), UALCAN, and Gene Expression Omnibus (GEO) databases. Microarray and bioinformatic analyses identified upregulated CENP-A/E/F/H/I/K/P/W and HJURP in stomach adenocarcinoma (STAD), but not in signet ring cell carcinoma (SRCC). Significantly higher CENP-I mRNA expression was also confirmed in 40 pairs of GC tissues than in paired normal gastric tissues by qRT-PCR (P<.001). IHC showed that elevated CENP-I expression was associated with higher tumor stage, lymph node invasion, increased HER2-positive rate (36.7% vs 10.0%), and intestinal Lauren classification in 69 GC samples compared to paired paracancerous normal tissues. The survival of the high-CENP-I group members was poor compared with that of the low-CENP-I group (P = .0011). Cox univariate regression analysis identified tumor size (P = .008), HER2 status (P = .027), and CENP-I expression (P = .049) were independent prognostic factors of GC. The cellular function of CENP-I was studied in MKN45 and MKN28 GC cell lines in vitro. Cell proliferation, migration, and apoptosis were determined using CCK-8, transwell assay, TUNEL assay, and flow cytometry. Our results showed that CENP-I promoted GC cell proliferation, inhibited apoptosis, facilitated cell migration, and induced epithelial-mesenchymal transition (EMT), possibly by activating the AKT pathway. CENP-I expression was correlated with genetic signatures of the proliferative subtype of GC, characterized by intestinal Lauren classification, HER2 amplification, and TP53 mutation. In conclusion, this study revealed an elevated CENP-I expression in GC, which was associated with malignant features and poor prognosis of GC patients, and identified its function in modulating cell proliferation, apoptosis, and migration.

Performance of cervical cancer screening and triage strategies among women living with HIV in China.

OBJECTIVES: To evaluate the clinical performance of liquid-based cytology (LBC), HPV tests and visual inspections with acetic acid or Lugol's iodine (VIA/VILI) as primary screening and triage strategies among Chinese women living with HIV (WLHIV). METHODS: WLHIV aged 18 years and older were recruited from HIV/AIDS treatment clinic in Yunnan, China from 2019 to 2020. Women were screened with self- and physician-sampling for HPV tests, LBC, and VIA/VILI. Women positive for any HPV or with cytological abnormalities were recalled for colposcopy examination and biopsy when necessary. Clinical performance of primary and triage strategies for detecting cervical intraepithelial neoplasia grade 2 or worse (CIN2+) was evaluated. RESULTS: For primary screening, sensitivity of physician-HPV tests was 100%, 89.5%, and 100% for hybrid capture 2 (HC2), cobas, and Sansure HPV, and specificity was 80.4%, 85.1%, and 72.0%, respectively. Self-HPV test achieved considerable performance with physician-HPV. Sensitivity and specificity were 61.1% and 96.3% for LBC (atypical squamous cells of undetermined significance or worse [ASCUS+]), 40.0% and 77.3% for VIA/VILI. For triaging HPV-positive women, LBC (ASCUS+), HPV-16/18 genotyping, and VIA/VILI-elevated specificity with sensitivity declined 30%-50% compared with HPV screening alone. Restricted HPV genotyping triage (HPV-16/18/31/33/45/52/58) demonstrated the optimal accuracy (89.5% sensitivity, 81.9% specificity), and was similar to HPV-16/18 with reflex LBC (ASCUS+). Combination antiretroviral therapies (cARTs) <2 years were associated with decreased specificity of HC2 (aOR: 1.87, 95% CI: 1.22-3.91) and Sansure HPV (2.48, 1.43-4.29). CONCLUSIONS: Self-HPV with restricted genotyping triage is highly recommended for cervical cancer screening for WLHIV in China. Feasible triage to increase HPV specificity among women with short duration of cART is needed.

HOXB13 promotes gastric cancer cell migration and invasion via IGF-1R upregulation and subsequent activation of PI3K/AKT/mTOR signaling pathway.

AIMS: This study aimed at exploring HOXB13 expression and function in gastric cancer (GC), and the underlying molecular mechanism. MATERIALS AND METHODS: HOXB13 and fat mass and obesity-associated protein (FTO) expression in GC and non-GC tissues of GC patients were analyzed using Gene Expression Profiling Interactive Analysis (GEPIA) and verified by quantitative reverse transcription-polymerase chain reaction (RT-qPCR) and western blotting. The regulatory relationship between FTO and HOXB13 was verified via RT-qPCR, methylated RNA immunoprecipitation sequencing (MeRIP-seq), and double luciferase reporter gene assay. The effects of HOXB13 and FTO on proliferation, invasion, and migration of GC cells were studied using EdU and Transwell assays. KEY FINDINGS: HOXB13 and FTO expression was abnormally high in GC tissues and cell lines, with no significant correlation between HOXB13 and FTO expression and the prognosis of GC patients. Inhibiting FTO expression in GC cells decreased HOXB13 methylation and upregulated HOXB13 expression. Inhibiting HOXB13 and FTO expression suppressed GC cell proliferation, migration, and invasion. Decreased HOXB13 expression suppressed PI3K/AKT/mTOR signaling pathway activity, while atypical HOXB13 expression promoted it. A probable downstream target of HOXB13 was insulin-like growth factor 1 receptor (IGF-1R); a decrease in IGF-1R relieved GC cell migration, invasion, and proliferation and inhibited PI3K/AKT/mTOR signaling pathway activity promoted by atypical HOXB13 expression. SIGNIFICANCE: HOXB13 and FTO expression is elevated in GC. FTO suppresses HOXB13 methylation; FTO and HOXB13 expression promotes GC cell proliferation, migration, and invasion. HOXB13 expression intensifies GC invasion through PI3K/AKT/mTOR signaling via IGF-1R. HOXB13 and associated signaling pathways can be effective targets for GC therapy.

Understanding women's perspectives on breast cancer is essential for cancer control: knowledge, risk awareness, and care-seeking in Mwanza, Tanzania.

BACKGROUND: Breast Cancer is the most common cancer in women worldwide. Since 2008, Mwanza, Tanzania, has worked to provide comprehensive cancer services through its Zonal consultant hospital. New national guidelines focused on clinical breast exam requires that women be aware of and seek care for breast concerns. Therefore, this study aims to understand breast cancer awareness in Mwanza and describe women-level barriers, care-seeking behavior, and perspectives on breast cancer. METHODS: A community-based survey was administered to conveniently sampled women aged 30 and older to assess women's perspectives on breast cancer and care-seeking behavior. RESULTS: Among 1129 women with a median age of 37 (IQR: 31-44) years, 73% have heard of cancer and 10% have received breast health education. Women self-evaluated their knowledge of breast cancer (from 1-none to 10-extremely knowledgeable) with a median response of 3 (IQR: 1-4). Only 14% felt they knew any signs or symptoms of breast cancer. Encouragingly, 56% of women were fairly-to-very confident they would notice changes in their breasts, with 24% of women practicing self-breast examination and 21% reporting they had received a past breast exam. Overall, 74% said they would be somewhat-to-very likely to seek care if they noticed breast changes, with 96% noting severity of symptoms as a motivator. However, fear of losing a breast (40%) and fear of a poor diagnosis (38%) were most frequent barriers to care seeking. In assessing knowledge of risk factors, about 50% of women did not know any risk factors for breast cancer whereas 42% of women believed long term contraceptive use a risk factor. However, 37% and 35% of women did not think that family history or being older were risk factors, respectively. CONCLUSIONS: The success of efforts to improve early diagnosis in a setting without population-based screening depends on women being aware of breast cancer signs and symptoms, risks, and ultimately seeking care for breast concerns. Fortunately, most women said they would seek care if they noticed a change in their breasts, but the low levels of cancer knowledge, symptoms, and common risk factors highlight the need for targeted community education and awareness campaigns.

Development and Validation of an Automatic Image-Recognition Endoscopic Report Generation System: A Multicenter Study.

INTRODUCTION: Conventional gastrointestinal (GI) endoscopy reports written by physicians are time consuming and might have obvious heterogeneity or omissions, impairing the efficiency and multicenter consultation potential. We aimed to develop and validate an image recognition-based structured report generation system (ISRGS) through a multicenter database and to assess its diagnostic performance. METHODS: First, we developed and evaluated an ISRGS combining real-time video capture, site identification, lesion detection, subcharacteristics analysis, and structured report generation. White light and chromoendoscopy images from patients with GI lesions were eligible for study inclusion. A total of 46,987 images from 9 tertiary hospitals were used to train, validate, and multicenter test (6:2:2). Moreover, 5,699 images were prospectively enrolled from Qilu Hospital of Shandong University to further assess the system in a prospective test set. The primary outcome was the diagnosis performance of GI lesions in multicenter and prospective tests. RESULTS: The overall accuracy in identifying early esophageal cancer, early gastric cancer, early colorectal cancer, esophageal varices, reflux esophagitis, Barrett's esophagus, chronic atrophic gastritis, gastric ulcer, colorectal polyp, and ulcerative colitis was 0.8841 (95% confidence interval, 0.8775-0.8904) and 0.8965 (0.8883-0.9041) in multicenter and prospective tests, respectively. The accuracy of cecum and upper GI site identification were 0.9978 (0.9969-0.9984) and 0.8513 (0.8399-0.8620), respectively. The accuracy of staining discrimination was 0.9489 (0.9396-0.9568). The relative error of size measurement was 4.04% (range 0.75%-7.39%). DISCUSSION: ISRGS is a reliable computer-aided endoscopic report generation system that might assist endoscopists working at various hospital levels to generate standardized and accurate endoscopy reports (http://links.lww.com/CTG/A485).

Diagnosis and treatment of adult mixed-type Henoch-Schönlein purpura.

AIM OF THE STUDY: The purpose of this study was to investigate the clinical manifestations and outcomes of patients with adult mixed-type Henoch-Schönlein purpura (HSP) and imaging characteristics of the disease, and to evaluate the efficacy of combined therapy in treating symptoms of HSP. MATERIAL AND METHODS: From January 2008 to October 2015, 23 patients with adult mixed-type HSP were enrolled. Abdominal contrast-enhanced computed tomography (CT) examination and small intestinal enteroscopy were performed for all the patients. For patients with positive urine protein, ultrasonic guided renal needle biopsy with 18G biopsy needle was performed; immunofluorescence and pathologic examinations were performed. Combined therapy with antihistamine drugs, gastric acid suppressants and glucocorticoids was used to relieve abdominal pain, gastrointestinal tract bleeding and urine protein. RESULTS: The typical skin manifestation of HSP is distributed purpura in dependent areas. Abdominal contrast-enhanced CT examination exhibited the intestinal canal wall thickening and edema. Small intestinal endoscopy showed diffused hyperemia, dropsy, and erosion. All the patients with positive urine protein showed significantly higher IgA levels. With the use of combined therapy, abdominal pain and gastrointestinal tract bleeding disappeared, and urine protein decreased gradually. CONCLUSIONS: Higher IgA levels with multiorgan involvement (gastrointestinal, kidney and skin) should make one consider the diagnosis. The combined examination of abdominal contrast-enhanced CT, small intestinal endoscopy and renal needle biopsy is a valuable method for the early diagnosis of adult mixed-type HSP.

LncRNA GAS5-mediated miR-1323 promotes tumor progression by targeting TP53INP1 in hepatocellular carcinoma.

Background: MiR-1323 was identified in 2006. Until now, the roles and mechanisms of miR-1323 in the progression of cancers including hepatocellular carcinoma (HCC) remain unknown. The aim of this study was to investigate the expressions, roles and mechanisms of miR-1323 in HCC development. Methods: QRT-PCR was used to evaluate the expressions of miR-1323, GAS5 and TP53INP1 in HCC tissues and cell lines. CCK-8 assay, transwell invasion assay and flow cytometry assay were conducted to evaluate the proliferation, invasion and apoptosis of HCC cells. Luciferase assay was used to identify microRNA-target interaction. Results: Firstly, our results showed that miR-1323 promoted proliferation and invasion, and inhibited apoptosis of HCC cells. Secondly, we found that TP53INP1 was a direct target of miR-1323 and could reverse the effects of miR-1323 on proliferation, invasion and apoptosis of HCC cells. Thirdly, our results showed that long non-coding RNA (lncRNA) GAS5 and miR-1323 could interact with each other and affect biological processes of HCC cells. Furthermore, we identified the negative correlations between miR-1323 and TP53INP1, and between miR-1323 and GAS5 in tumor tissues of patients with HCC. Conclusion: Taken together, our study revealed the important roles of GAS5/miR-1323/TP53INP1 axis in HCC progression. This study also provided promising strategies for targeted therapy of patients with HCC.

MiR-29b suppresses proliferation and mobility by targeting SOX12 and DNMT3b in pancreatic cancer.

Pancreatic cancer is one of the leading causes of solid carcinoma with the worst survival rate. The reasons for the worst survival rate include the lack of biomarkers for early detection, diagnosis at a late stage, and the limitation of the current therapy. Further study to investigate the underlying molecular mechanism in pancreatic cancer patients is necessary. A previous study showed that the miR-29b expression level is dysregulated, suggesting that it may serve an important function in pancreatic cancer. The CCK8 assay and the colony formation assay were used to detect the proliferation ability of the treated pancreatic cancer cells; a wound-healing assay and a transwell assay were used to test the migration and invasion ability and the interactive action of miR-29b and SOX12 or DNMT3b was examined by a luciferase assay. Cell proliferation, migration, and invasion were attenuated by miR-29b, whereas knockdown of SOX12 and DNMT3b could block SW1990 malignant activity. Further, the double luciferase assay showed that miR-29b can target SOX12 and DNMT3b directly by binding to their 3'-untranslated region. Finally, a rescue experiment was conducted by transfecting miR-29b and SOX12 overexpressed plasmid into cells. Cell proliferation, migration, and invasion inhibition induced by miR-29b were reversed by SOX12 overexpression, and revail of the expression of DNMT3b. MiR-29b suppressed proliferation, migration, and invasion by directly targeting SOX12 and DNMT3b in pancreatic cancer cells, and DNMT3b might be a target gene of SOX12.

Endoscopic full-thickness resection for gastric gastrointestinal stromal tumor originating from the muscularis propria.

OBJECTIVE: This study retrospectively reviewed 46 cases of gastric gastrointestinal stromal tumors treated by endoluminal endoscopic full-thickness resection (EFR) microsurgery in our gastrointestinal endoscopy center. We aimed to evaluate the EFR for the treatment of gastric gastrointestinal stromal tumors originating from the muscularis propria. METHODS: A total of 46 patients with gastric gastrointestinal stromal tumors originated from the muscularis propria layer from January 2012 to June 2015 were treated with EFR. The patients were followed up with gastroscope and computed tomography (CT) for evaluation of therapeutic effect and safety. RESULTS: EFR was successfully accomplished to remove all tumors in 46 patients. The mean procedure time was 82.5±39.8min (56-188min). Except in 3 leiomyomas, pathological examination confirmed gastrointestinal stromal tumor (GIST) in 43 cases. None of the patients had occurred bleeding, peritonitis and other complications after EFR. Thereafter, all patients were followed up with gastro-scope after 1, 6,12 months. CONCLUSIONS: EFR is effective and safe for patients with gastric gastrointestinal stromal tumors originated from muscularis propria layer and has the advantage of less invasive treatment and higher tumor resection rate. It should be considered for further application.

miR-23b-3p and miR-130a-5p affect cell growth, migration and invasion by targeting CB1R via the Wnt/ß-catenin signaling pathway in gastric carcinoma.

BACKGROUND: Gastric cancer (GC) is the most common malignancy and third leading cause of cancer mortality worldwide. The identification of a sensitive biomarker as well as effective therapeutic targets for the treatment of GC is of critical importance. microRNAs play significant roles in the development of cancer and may serve as promising therapeutic targets. METHODS: The mRNA and protein expression of CB1R were studied both in GC cells and tissues. GC cell lines with specific gene overexpression and knockdown vectors were constructed. CCK-8 assay, matrigel invasion and colony formation assays were performed to evaluate the proliferation and invasion abilities. The binding and regulatory effects of miR-23b-3 and miR-130a-5p on CB1R mRNA were investigated using a luciferase reporter assay. Western blot analysis was performed to explore the potential interaction proteins of CB1R. RESULTS: In the present study, it was demonstrated that the cannabinoid receptor 1 (CB1R) was overexpressed, and miR-23b-3p and miR-130a-5p were downregulated, in GC cells. In addition, the results revealed that these effects are associated with malignant biological behaviors exhibited by GC cells. Furthermore, miR-23b-3p and miR-130a-5p may regulate CB1R expression via the Wnt/ß-catenin signaling pathway. CONCLUSION: Our results suggested dysregulation of CB1R expression is closely related to the malignant biological behavior of gastric cancer cells. miRNA/CB1R-based therapy may represent a promising therapeutic strategy for the clinical treatment of GC patients.

Endoscopic full-thickness resection for gastric gastrointestinal stromal tumor originating from the muscularis propria

SUMMARY OBJECTIVE: This study retrospectively reviewed 46 cases of gastric gastrointestinal stromal tumors treated by endoluminal endoscopic full-thickness resection (EFR) microsurgery in our gastrointestinal endoscopy center. We aimed to evaluate the EFR for the treatment of gastric gastrointestinal stromal tumors originating from the muscularis propria. METHODS: A total of 46 patients with gastric gastrointestinal stromal tumors originated from the muscularis propria layer from January 2012 to June 2015 were treated with EFR. The patients were followed up with gastroscope and computed tomography (CT) for evaluation of therapeutic effect and safety. RESULTS: EFR was successfully accomplished to remove all tumors in 46 patients. The mean procedure time was 82.5±39.8min (56-188min). Except in 3 leiomyomas, pathological examination confirmed gastrointestinal stromal tumor (GIST) in 43 cases. None of the patients had occurred bleeding, peritonitis and other complications after EFR. Thereafter, all patients were followed up with gastro-scope after 1, 6,12 months. CONCLUSIONS: EFR is effective and safe for patients with gastric gastrointestinal stromal tumors originated from muscularis propria layer and has the advantage of less invasive treatment and higher tumor resection rate. It should be considered for further application.

RESUMO OBJETIVO: Este estudo revisou retrospectivamente 46 casos de tumores gástricos estromáticos gastrointestinais tratados por microcirurgia endoluminal endoscópica de ressecção completa (EFR) em nosso centro de endoscopia gastrointestinal. Pretendemos avaliar a EFR para o tratamento de tumores gastrointestinais estromáticos originários da muscularis própria. MÉTODOS: Um total de 46 pacientes com tumores gástricos estromáticos gastrointestinais originários da camada muscular própria, de janeiro de 2012 a junho de 2015, foi tratado com EFR. Os pacientes foram acompanhados com gastroscópio e tomografia computadorizada (TC) para avaliação de efeitos terapêuticos e segurança. RESULTADOS: A EFR foi realizada com sucesso para remover todos os tumores em 46 pacientes. O tempo médio de procedimento foi de 82,5±39,8 min (56-188 min). Exceto em três leiomiomas, exame patológico confirmou tumor estromal gastrointestinal (Gist) em 43 casos. Em nenhum paciente ocorreu sangramento, peritonite e outras complicações após EFR. Posteriormente, todos os pacientes foram acompanhados com gastroscópio após um, seis e 12 meses. CONCLUSÕES: A EFR é eficaz e segura para pacientes com tumores gastrointestinais originários da camada muscular própria e tem a vantagem de ser um tratamento menos invasivo e com maior taxa de ressecção tumoral. Deve ser considerada para posterior aplicação.

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. If a 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 obstruction 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.

Downregulation of miR­29b targets DNMT3b to suppress cellular apoptosis and enhance proliferation in pancreatic cancer.

As one of the most aggressive types of tumor, pancreatic cancer is a principal cause of tumor­associated mortality. Negative associations between microRNA­29 (miR­29) and DNA methyltransferases (DNMT) 3a and 3b have been demonstrated to be associated with the carcinogenesis of a number of types of cancer; however, this has not been completely elucidated in pancreatic cancer. In the present study, pancreatic cancer tissues (n=15) and corresponding paracancerous tissues (n=15) were obtained and the results of reverse transcription­quantitative polymerase chain reaction analysis indicated decreased expression of miR­29b and enhanced mRNA expression of DNMT3b in pancreatic cancer tissues, compared with the corresponding paracancerous tissues. Increased protein expression of DNMT3b was demonstrated by western blotting and immunohistochemistry. In addition, the negative association between miR­29b and DNMT3b was noted in pancreatic cancer tissues, and luciferase reporter assays confirmed that miR­29b was able to directly target DNMT3b in vitro. Notably, miR­29b overexpression was able to decrease cell viability and to promote the apoptosis by targeting DNMT3b, and the knockdown of DNMT3b exhibited consistent results in vitro and in vivo. The results of the present study suggested that miR­29b, as a tumor suppressor, may be a novel target for the development of treatments for pancreatic cancer.