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1.
Am J Cancer Res ; 13(6): 2670-2680, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37424822

RESUMO

MicroRNAs play significant roles in cancer initiation and progression. Exosomes are important extracellular vesicles for transporting molecules to distant sites. This study aims to investigate the functional roles of miR-410-3p in primary gastric cancer, as well as the roles of exosomes in regulating expression of miR-410-3p. In this study, forty-seven pairs of human gastric cancer tissue samples were collected. Endogenous expression of miR-410-3p in tissue samples and cell lines, and expression of exosomal miR-410-3p in cell culture medium were evaluated by RT-qPCR. Functional assays including cell proliferation assay by MTT, cell migration and invasion assay by transwell, and cell adhesion assay were performed. Targets of miR-410-3p were screened. Cell culture medium of culturing cell lines established from stomach (AGS and BCG23) was applied for culturing cell lines established from other sites (MKN45 and HEK293T). It was found that miR-410-3p was significantly downregulated in gastric cancer. Overexpression of miR-410-3p inhibited gastric cancer cell proliferation, migration, and invasion. MiR-410-3p mimic enhanced cell adhesion. HMGB1 was a target of miR-410-3p in primary gastric cancer. Expression of exosomal miR-410-3p in cell culture medium was dramatically higher than its endogenous expression. Exosomes from cell culture medium of AGS or BCG23 regulated endogenous expression of miR-410-3p in MKN45. In conclusion, miR-410-3p functioned as a tumor suppressor in primary gastric cancer. MiR-410-3p was higher expressed in exosomes of cell culture medium than its endogenous expression in cells. Endogenous expression of miR-410-3p in a distant site could be regulated by exosomes from the original site.

2.
BMC Med Educ ; 23(1): 5, 2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36600224

RESUMO

AIM: The global pandemic of COVID-19 has led to extensive practice of online learning. Our main objective is to compare different online synchronous interactive learning activities to evaluate students' perceptions. Moreover, we also aim to identify factors influencing their perceptions in these classes. METHODS: A cross-sectional, questionnaire-based study focusing on clinical year medical students' perceptions and feedback was conducted between February 2021 -June 2021 at the University of Hong Kong. Online learning activities were divided into bedside teaching, practical skill session, problem-based learning (PBL) or tutorial, and lecture. A questionnaire based on the Dundee Ready Education Environment Measure (DREEM) was distributed to 716 clinical year students to document their perceptions. RESULTS: One hundred responses were received with a response rate of 15.4% (110/716, including 96 from bedside teaching, 67 from practical skill session, 104 from PBL/tutorial, and 101 from lecture). For the mean score of the DREEM-extracted questionnaire, online PBL/tutorial scored the highest (2.72 ± 0.54), while bedside scored the lowest (2.38 ± 0.68, p = 0.001). Meanwhile, there was no significant difference when we compared different school years (p = 0.39), age (p = 0.37), gender (p = 1.00), year of internet experience (<17 vs ≥17 years p = 0.59), or prior online class experience (p = 0.62). When asked about students' preference for online vs face-to-face classes. Students showed higher preferences for online PBL/tutorial (2.06 ± 0.75) and lectures (2.27 ± 0.81). Distraction remains a significant problem across all four learning activities. A multivariate analysis was performed regarding students' reported behavior in comparison with their perception through the DREEM-extracted questionnaire. The results showed that good audio and video quality had a significant and positive correlation with their perception of online bedside teaching, practical skill sessions, and PBL/tutorial. It also showed that the use of the video camera correlated with an increase in perception scores for lectures. CONCLUSION: The present analysis has demonstrated that students' perception of different online synchronous interactive learning activities varies. Further investigations are required on minimizing distraction during online classes.


Assuntos
COVID-19 , Educação a Distância , Educação de Graduação em Medicina , Estudantes de Medicina , Humanos , COVID-19/epidemiologia , Estudos Transversais , Pandemias , Percepção , Inquéritos e Questionários
3.
Am J Cancer Res ; 12(10): 4680-4692, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36381319

RESUMO

Gastric cancer is one of the leading causes of cancer death in the world. Early diagnosis and effective chemotherapy are vital to reduce the overall mortality. Prostaglandin E2 (PGE2) has been implicated as an important factor in gastric cancer carcinogenesis. ECF based regimen (epirubicin, cisplatin, 5-fluorouracil) is the first-line chemotherapy for advanced gastric cancer. However, patients develop resistance after chemotherapy. The aim of this study is sought to investigate the role of EP2 receptor, a PGE2 receptor, and the antagonism of EP2 receptor in response to ECF treatment. Expression of EP2 receptor was evaluated in gastric cancer tissue samples and cell lines. Cell proliferation and cell apoptosis assays were performed in vitro and in vivo, upon knockdown of EP2 receptor, antagonist of EP2 receptor and/or ECF treatment. Western Blot was applied for evaluation of proteins relating to cell cycle, apoptosis and drug transporter. Next generation sequencing and ingenuity pathway analysis were applied for screening for downstream targets of EP2 receptor. Expressions of the targets of EP2 receptor were further evaluated in gastric cancer cells and tissues. In this study, we found that expression of EP2 receptor was significantly upregulated in gastric cancer. Inhibition of EP2 receptor reduced gastric cancer cell proliferation, induced cell cycle arrest proteins, and enhanced cell apoptosis. Moreover, knockdown of EP2 receptor by siRNA or antagonist sensitized gastric cancer cells to ECF. Silence of EP2 receptor also significantly abrogated gastric cancer growth in a mice model. Analysis revealed that CAV1 was a downstream target of EP2 receptor in gastric cancer. Our findings illustrated that blocking EP2 receptor reduced tumor growth and induced apoptosis in gastric cancer. This novel study unraveled CAV1 was a downstream target of EP2 receptor. Antagonizing EP2 receptor could be a potential therapeutic target in gastric cancer, in particular those with high EP2 receptor expression.

4.
Heliyon ; 8(1): e08744, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35036612

RESUMO

INTRODUCTION: A new Online interactive Ultrasound Teaching (OUT) was developed in our institution in March 2021 during COVID-19 outbreak. METHODS: This is a case control study on 65 final year medical students to compare OUT with conventional face-to-face ultrasound tutorials. There were 31 female and 34 male students. Median age was 23 years old (Range 21-30). Students were randomly assigned into two different teaching groups. Competency in conducting ultrasonic exam was assessed by Objective Structured Assessment of Ultrasound Skills (OSAUS). RESULTS: 32 students were randomized into the control group (face to face teaching) while 33 students were randomized into the case group (OUT). Baseline demographic characteristics were comparable between the two groups (p > 0.05).The median score of the blinded OSAUS assessment was 5.5 (Range 3-7). There were 4 (6.2%) students who failed in the assessment (scored <4 out of 7), and 10 (15.4%) students scored full marks in the assessment.The medians scores were 5.5 (Range 3-7), and 6 (Range 3-7) (p = 0.8057) in the control and case groups respectively. 6 (18.8%) students in the control group scored full mark, comparing to 4 (12.1%) students in the case group (p = 0.5105). 2 students from each group failed the assessment (p = 1). CONCLUSION: Ultrasonographic skills performance was comparable between students who were taught by OUT and conventional face-to-face tutorial.

5.
Surgeon ; 20(5): e195-e205, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34483055

RESUMO

Rapid development of COVID-19 has resulted in a massive shift from traditional to online teaching. This review aims to evaluate the effectiveness of distance learning on anatomy and surgical training. This systematic review was conducted in line with the PRISMA statement and current methodological literature. The databases CINAHL, Cochrane, EMBASE and Pubmed were searched using the search terms "Distant learning" OR "Distance learning" AND "Anatomy OR Surgery". 182 non-duplicate studies were identified. 20 studies were included for qualitative analysis. 10 studies evaluated students' performance with distance learning. 3 studies suggested that students' learning motivation improved with distance learning pedagogy. 5 studies found improved student performance with distance learning (performance or task completion time) when compared to conventional physical method. While 2 other studies found non-inferior student performance. 10 studies evaluated students' feedback on distance learning. Most feedbacks were positive, with flexibility, efficiency, increased motivation and better viewing angles as the most-liked features of distance teaching. 4 studies pointed out some limitations of distance learning, including the lack of personal contact with tutor, poor network and reduced student concentration. 7 studies evaluated tutors' feedback on distance learning. Tutors generally liked online platforms for the ease of tracking silent students, monitoring performance and updating fast-changing knowledge. Yet the lack of hands-on experience for students, technical issues and high costs are the main concerns for tutors. In conclusion, distance learning is a feasible alternative for anatomy and surgical teaching.


Assuntos
COVID-19 , Educação a Distância , Estudantes de Medicina , COVID-19/epidemiologia , Humanos , Ensino
6.
BMC Med Educ ; 21(1): 141, 2021 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-33658015

RESUMO

BACKGROUND: Educational pedagogies were modified during the COVID-19 pandemic to minimise interruption to teaching. One approach has been the distance learning problem-based learning (PBL) tutorial utilising the online peer-to-peer platform. The aim of this study was to compare the performance of students using distance learning PBL tutorials using with that of students utilising the conventional face-to-face approach. METHODS: This retrospective study was conducted in a single academic institution. We compared two groups of fourth-year medical students from the same class: one group used distance learning (DL); the other, the face-to-face (FF) method. We used students' baseline performance at the preceding block for one-to-one propensity score matching. Students utilising the PBL tutorial were given grades by their tutors according to a standardised scoring system encompassing five key areas (score range: 0-10). The main outcome was a student's total score (i.e., the sum of the scores from the five key areas, ranging from 0 to 50). RESULT: We matched 62 students in each group. With four tutorials, there were 490 observations, with 245 in each group. The mean total score for the DL group was 37.5 ± 4.6, which was significantly lower than that of the FF group (39.0 ± 4.4, p < 0.001). We noted that students in the DL group had a significantly lower scores for all five areas of proficiency: participation, communication, preparation, critical thinking and group skills. CONCLUSION: Findings of this study revealed that the performance of students utilising the DL PBL tutorials was lower than that of students participating in the conventional FF approach. Further studies are needed to ascertain the underlying cause.


Assuntos
COVID-19/epidemiologia , Educação a Distância , Educação de Graduação em Medicina/métodos , Pandemias , Aprendizagem Baseada em Problemas/métodos , Sucesso Acadêmico , Feminino , Hong Kong/epidemiologia , Humanos , Masculino , Estudos Retrospectivos , SARS-CoV-2 , Adulto Jovem
7.
Surg Today ; 51(8): 1404-1409, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33492484

RESUMO

PURPOSE: Medical education has been disrupted by the COVID-19 pandemic in many countries, with face-to-face lectures replaced by pre-recorded videos. However, surgical skills training cannot be replaced easily by videos, as a high level of tutor-student interaction is required. Thus, we developed a new web-based surgical skill learning session (WSSL). This case-control study evaluates the surgical skills competency of medical students taught by the WSSL. METHODS: This case-control study compares WSSL with face-to-face tutorials. Students were assigned randomly to one of two groups according to the teaching method. Independent blinded assessment was performed by a standardized marking scheme, modified from the Objective Structured Assessment of Technical Skills (OSATS) global rating scale. RESULTS: We recruited 62 final-year medical students into the study, with 33 randomized to the face-to-face teaching group (control group), and 29 to the WSSL group(case group) according to their student number. The baseline demographic characteristics of the two groups were comparable. The mean score at the clinical competency assessment of the control group was 4.8/5 (range 4-5) and that of the case group was 4.7/5 (range 4-5) (p = 1). There were no difficulties with program or hardware installation reported by the WSSL students. CONCLUSIONS: Surgical skills performance was comparable between students who were taught by the WSSL and those taught by conventional face-to-face tutorials.


Assuntos
COVID-19/epidemiologia , Competência Clínica , Instrução por Computador , Educação de Graduação em Medicina/métodos , Cirurgia Geral/educação , Estudos de Casos e Controles , Currículo , Avaliação Educacional , Feminino , Humanos , Internet , Masculino , Pandemias , SARS-CoV-2 , Adulto Jovem
8.
Surg Pract ; 24(3): 105-109, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32837531

RESUMO

Introduction: Due to the COVID-19 outbreak, all on-site undergraduate medical teaching activities in Hong Kong have been suspended. A new web-based surgical skills learning (WSSL) for basic surgical skills training that were normally taught face-to-face was developed. Methodology: Basic surgical skills were taught with normal face-to-face tutorial to 30 final year medical students prior to the outbreak. The same group of students were invited to join the online WSSL using Zoom. Evaluation of WSSL was performed by a standardized questionnaire. Results: Thirty final year medical students (16 female, 14 male students) were recruited into the study. Median age was 23 (range 22-24). Most of them believed that WSSL is easy to follow. When compared to face-to-face teaching. Most students (N = 22, 73.4%) felt that WSSL was just as difficult/easy as conventional teaching for learning instrumental knots. Students were asked to evaluate WSSL by using a Likert scale of 1 to 10 (with 10 being highly recommended). Twelve (40%) students highly recommended WSSL (Score 9 to 10), 15 students (50%) slightly recommended WSSL (Score 6-8). Conclusion: Web-based surgical skills learning is a feasible alternative for face-to-face surgical skills teaching.

9.
J Cell Mol Med ; 24(11): 6220-6232, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32383554

RESUMO

Exosomes secreted by living cancer cells can regulate metastasis. Exosomal miRNAs can reflect pathological conditions of the original cancer cells. Therefore, we aim to identify exosomal miRNAs as circulating biomarkers for haematogenous metastasis of gastric cancer. Pre-treatment serum samples of eighty-nine patients with stage II/III gastric cancer were collected. Thirty-four of them developed haematogenous metastasis after surgery and the other fifty-five did not. Extraction of exosomes was validated by western blot, transmission electron microscopy and nanoparticle tracking analysis. MiRNA qPCR array was performed in three matched pairs of samples. Internal control was selected from PCR array and validated in the remaining samples. Expressions of exosomal miRNAs were evaluated in the remaining samples by RT-qPCR, as well as in gastric cancer tissue samples and cell culture medium. Expression levels of exosomal miRNAs were analysed with clinical characteristics. The results indicated thirteen up-regulated and six down-regulated miRNAs were found after normalization. MiR-379-5p and miR-410-3p were significantly up-regulated in metastatic patients (P < .01). Higher expression of exosomal miR-379-5p or miR-410-3p showed shorter progression-free survival of the patients (P < .05). It was also found that miR-379-5p and miR-410-3p were down-regulated in gastric cancer tissue samples, while they were significantly up-regulated in gastric cancer cell culture medium compared with cancer cells. In conclusion, exosomal miRNAs are promising circulating biomarkers for prediction of development of haematogenous metastasis after surgery for stage II/III gastric cancer.


Assuntos
Biomarcadores Tumorais/genética , Exossomos/genética , MicroRNAs/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/cirurgia , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Meios de Cultura , Exossomos/ultraestrutura , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , MicroRNAs/sangue , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Metástase Neoplásica , Intervalo Livre de Progressão , Reprodutibilidade dos Testes , Neoplasias Gástricas/sangue , Neoplasias Gástricas/ultraestrutura
10.
EBioMedicine ; 52: 102661, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32062358

RESUMO

BACKGROUND: Progressive peritoneal fibrosis is a common complication in patients on long-term peritoneal dialysis (PD). PD-associated peritonitis is a major exacerbating factor. We investigated the anti-fibrotic properties of decorin secreted by peritoneal mesothelial cells. METHODS: Dialysate decorin level in stable PD patients and those with peritonitis was measured. In vitro experiments were conducted to investigate the effect of decorin in fibrotic response in human peritoneal mesothelial cells (HPMC). FINDINGS: Increasing PD duration was associated with a progressive decrease of dialysate decorin and CA125 levels. Dialysate decorin level correlated with CA125 level. Peritonitis episodes were associated with a massive drop of dialysate decorin, which persisted for over three months despite clinical recovery. Dialysate decorin level correlated with that of TGF-ß1, but was inversely related to IL-1ß and IL-8. TGF-ß1, IL-1ß, IL-6, IL-8, or TNF-α reduced decorin secretion in HPMC, but induced fibronectin expression. The effects were mediated in part through increased p38 MAPK and AKT/PI3K phosphorylation. Decorin abrogated the induction of fibronectin expression in mesothelial cells by PD fluids or pro-fibrotic cytokines, through decreased TGF-ßRI, p38 MAPK and AKT/PI3K phosphorylation and increased glycogen synthase kinase-3ß phosphorylation. Decorin gene-silencing resulted in increased fibronectin expression under these conditions. INTERPRETATION: Our data demonstrate anti-fibrotic actions of decorin in HPMC, when these cells are subjected to the pro-fibrotic effect of peritoneal dialysate and pro-fibrotic cytokines in PD, especially during peritonitis.


Assuntos
Decorina/metabolismo , Diálise Peritoneal/efeitos adversos , Peritonite/etiologia , Peritonite/patologia , Idoso , Biomarcadores , Citocinas/metabolismo , Feminino , Fibronectinas/metabolismo , Fibrose , Técnicas de Silenciamento de Genes , Humanos , Masculino , Pessoa de Meia-Idade , Diálise Peritoneal/métodos
12.
Oncotarget ; 9(36): 24209-24220, 2018 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-29849934

RESUMO

MiR-92a has been shown to be dysregulated in various cancers and exhibited differential role in carcinogenesis. In this study, we sought to delineate the functional role of miR-92a and its regulatory pathway in gastric cancer. MiR-92a expression were underexpressed in tissues of gastric cancer patients with the area under curve (AUC) of 0.78. Low expression in plasma was due to the increased promoter DNA methylation of miR-92a. Overexpression of miR-92a inhibited cell proliferation and invasion, and induced apoptosis. Furthermore, miR-92a reduced tumor growth in xenograft model. EP4 and Notch 1 were identified to be negatively regulated by miR-92a, and involved in cell growth. Moreover, NF-κB expression was inversely correlated with miR-92a in gastric cancer tissues and suppressed the expression of miR-92. This study unravels the tumor suppressive role of miR-92a involving EP4/Notch 1 signaling regulated by NF-κB in gastric cancer. Further studies on miR-92a and EP4/Notch1 may provide a new treatment strategy for gastric cancer.

13.
Appl Immunohistochem Mol Morphol ; 26(4): 239-245, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-27490762

RESUMO

Human epidermal growth factor receptor 2 (HER2) dysregulation is associated with tumorigenesis in gastric/gastroesophageal junction cancer; however, the number of patients with HER2-positive disease is unclear, possibly due to differing scoring criteria/assays. Data are also lacking for early disease. We aimed to assess the HER2-positivity rate using approved testing criteria in a large, real-life multinational population. HER2-positivity was defined as an immunohistochemistry staining score of 3+, or immunohistochemistry 2+ and HER2 amplification detected by in situ hybridization. A total of 4949 patients were enrolled and results showed that 14.2% of 4920 samples with immunohistochemistry results were HER2-positive. HER2-positivity was significantly higher in males (16.1% vs. 9.6% in females), in gastroesophageal versus stomach tumors (22.1% vs. 12.9%), in biopsy versus surgical samples (18.3% vs. 13.0%), in intestinal tumor subtypes versus diffuse (21.5% vs. 4.8%) and mixed types (21.5% vs. 8.5%) (P<0.001), in mixed versus diffuse types (8.5% vs. 4.8%), and in "other" versus diffuse types (11.7% vs. 4.8%; P=0.002). There were no significant differences between stages. Patients in the youngest age percentile had significantly lower HER2-positivity rates than patients in the remaining percentiles (9.2% vs. 15.9%, 15.7%, and 15.1%; P<0.001). HER2-positivity was highest in France (20.2%) and lowest in Hong Kong (10.4%). In conclusion, HER-EAGLE, the first study of its kind to be conducted in a large, multinational population of almost 5000 patients, gives valuable insights into the real-world HER2-positivity rate in a gastric/gastroesophageal junction cancer patient population not selected for disease stage or histology.


Assuntos
Fatores Etários , Neoplasias Esofágicas/metabolismo , Junção Esofagogástrica/patologia , Receptor ErbB-2/metabolismo , Neoplasias Gástricas/metabolismo , Idoso , Ásia/epidemiologia , Brasil/epidemiologia , Canadá/epidemiologia , Detecção Precoce de Câncer , Neoplasias Esofágicas/epidemiologia , Europa (Continente)/epidemiologia , Feminino , Humanos , Imuno-Histoquímica , Cooperação Internacional , Masculino , Pessoa de Meia-Idade , Fatores Sexuais , Neoplasias Gástricas/epidemiologia
14.
Lab Invest ; 97(9): 1084-1094, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28581489

RESUMO

Metastasis increases the mortality rate of gastric cancer, which is the third leading cause of cancer-associated deaths worldwide. This study aims to identify the genes promoting metastasis of gastric cancer (GC). A human cell motility PCR array was used to analyze a pair of tumor and non-tumor tissue samples from a patient with stage IV GC (T3N3M1). Expression of the dysregulated genes was then evaluated in GC tissue samples (n=10) and cell lines (n=6) via qPCR. Expression of α-actinin-4 (ACTN4) was validated in a larger sample size (n=47) by qPCR, western blot and immunohistochemistry. Knockdown of ACTN4 with specific siRNAs was performed in GC cells, and adhesion assays, transwell invasion assays and migration assays were used to evaluate the function of these cells. Expression of potential targets of ACTN4 were then evaluated by qPCR. Thirty upregulated genes (greater than twofold) were revealed by the PCR array. We focused on ACTN4 because it was upregulated in 6 out of 10 pairs of tissue samples and 5 out of 6 GC cell lines. Further study indicated that ACTN4 was upregulated in 22/32 pairs of tissue samples at stage III &IV (P=0.0069). Knockdown of ACTN4 in GC cells showed no significant effect on cell proliferation, but significantly increased cell-matrix adhesion, as well as reduced migration and invasion of AGS, MKN7 and NCI-N87 cells. We found that NF-κB was downregulated in GC with the knockdown of ACTN4. In conclusion, this is the first study to indicate that ACTN4 is significantly upregulated in patients with metastatic GC. ACTN4 reduces cell adhesion and enhances migration and invasion of GC cells and may therefore be a novel therapeutic target for GC.


Assuntos
Actinina/análise , Actinina/metabolismo , Mucosa Gástrica/metabolismo , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Actinina/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Linhagem Celular Tumoral , Movimento Celular/genética , Estudos de Coortes , Feminino , Perfilação da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Masculino , Pessoa de Meia-Idade , NF-kappa B/análise , NF-kappa B/metabolismo , Estômago/química , Neoplasias Gástricas/química , Regulação para Cima/genética
15.
Sci Rep ; 7: 44935, 2017 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-28322295

RESUMO

The role of bacteria other than Helicobacter pylori (HP) in the stomach remains elusive. We characterized the gastric microbiota in individuals with different histological stages of gastric carcinogenesis and after receiving HP eradication therapy. Endoscopic gastric biopsies were obtained from subjects with HP gastritis, gastric intestinal metaplasia (IM), gastric cancer (GC) and HP negative controls. Gastric microbiota was characterized by Illumina MiSeq platform targeting the 16 S rDNA. Apart from dominant H. pylori, we observed other Proteobacteria including Haemophilus, Serratia, Neisseria and Stenotrophomonas as the major components of the human gastric microbiota. Although samples were largely converged according to the relative abundance of HP, a clear separation of GC and other samples was recovered. Whilst there was a strong inverse association between HP relative abundance and bacterial diversity, this association was weak in GC samples which tended to have lower bacterial diversity compared with other samples with similar HP levels. Eradication of HP resulted in an increase in bacterial diversity and restoration of the relative abundance of other bacteria to levels similar to individuals without HP. In conclusion, HP colonization results in alterations of gastric microbiota and reduction in bacterial diversity, which could be restored by antibiotic treatment.


Assuntos
Transformação Celular Neoplásica , Mucosa Gástrica/microbiologia , Mucosa Gástrica/fisiologia , Infecções por Helicobacter/complicações , Infecções por Helicobacter/microbiologia , Helicobacter pylori , Neoplasias Gástricas/etiologia , Neoplasias Gástricas/patologia , Biodiversidade , Feminino , Humanos , Masculino , Metagenoma , Metagenômica/métodos , Microbiota
16.
Tumour Biol ; 37(3): 3589-97, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26456959

RESUMO

It was reported that circulating microRNAs could be applied as non-invasive biomarkers for cancer monitoring. The purpose of this study was to identify plasma miRNA that may serve as a novel biomarker for gastric cancer and to evaluate its clinical application. MicroRNA profiles were generated from plasma samples of 5 patients with gastric cancer (GC) versus 5 healthy controls (HC). MicroRNA-940 (miR-940) was one of the most downregulated miRNAs with fold change of 0.164. It was revealed that the expression of miR-940 was downregulated in both the initial set (N = 30, P < 0.0001) and the validation set (N = 80, P < 0.0001) of plasma samples of patients with gastric cancer. The sensitivity was obviously higher than the current biomarkers CEA and CA19-9 (81.25 % vs. 22.54 % and 15.71 %). MiR-940 was also significantly downregulated in gastric cancer tissue samples (N = 34, P = 0.0015), as well as in cancer cell lines (N = 7). Importantly, miR-940 was significantly highly expressed in stomach tissue samples than in other types of tissue samples including the liver, breast, thyroid, and lung. Moreover, there was a trend of lower expression of miR-940 from early to advanced stage of gastric cancer. Target prediction suggested that miR-940 regulated cell signaling including NF-κB and Wnt/ß-catenin, as well as pathways of cell communication and adhesion. These pathways play critical roles in gastric cancer initiation and progression. It is the first report that miR-940 may mainly express in the stomach. Downregulation of plasma miR-940 may serve as a novel biomarker for detection of gastric cancer.


Assuntos
Biomarcadores Tumorais/genética , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Neoplasias Gástricas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Linhagem Celular Tumoral , Regulação para Baixo , Feminino , Humanos , Masculino , MicroRNAs/sangue , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Neoplasias Gástricas/sangue , Neoplasias Gástricas/patologia
17.
Mol Cancer ; 14: 202, 2015 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-26607322

RESUMO

BACKGROUND: Despite the declining incidence of gastric cancer, mortality rate remains high due to late presentation. We aimed to evaluate the sensitivity of miRNA as a diagnostic marker for gastric cancer in the circulation. METHODS: Plasma samples from 3 independent groups comprise 123 gastric cancer patients and 111 healthy controls for miRNA profiling from microarray screening. RESULTS: Microarray data showed that 25 miRNAs were upregulated in gastric cancer patients and 6 highly expressed miRNAs (miR-18a, miR-140-5p, miR-199a-3p, miR-627, miR-629 and miR-652) were selected for validation. In an independent validation set, levels of miR-627, miR-629 and miR-652 were significantly higher in gastric cancer patients than healthy controls (P <0.0001). An algorithm with improved sensitivity and specificity as gastric cancer classifier was adopted and validated in another random set of 15 plasma samples. Results showed that combination of 3 miRNAs obtained the highest area under curve, with a cut-off at 0.373, with a sensitivity of 86.7% and a specificity of 85.5%. CONCLUSION: This study revealed a three-miRNA signature as a promising classifier for gastric cancer, and greatly enhances the feasibility of circulating miRNAs as non-invasive diagnostic marker for this disease.


Assuntos
Biomarcadores Tumorais/sangue , MicroRNAs/sangue , Neoplasias Gástricas/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Progressão da Doença , Detecção Precoce de Câncer , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Neoplasias Gástricas/diagnóstico
19.
Hepatogastroenterology ; 62(139): 748-51, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-26897966

RESUMO

BACKGROUND/AIMS: Patients with gastric intestinal metaplasia and dysplasia are at increased risk of gastric cancer development. We tested the feasibility of using endoscopic radiofrequency ablation for the treatment of dysplasia and metaplasia in the stomach. METHODOLOGY: Patients who had histologically confirmed low-grade gastric dysplasia or IM were recruited. Endoscopic RFA was performed at 8 week-intervals for a maximum of 3 sessions. All patients were followed up by endoscopy until 12 months post-RFA. The primary outcome was the complete eradication of dysplasia or IM on follow-up. Secondary outcome was adverse events related to RFA. RESULTS: A total of 12 patients were recruited. Four patients had low-grade dysplasia and the remaining 8 patients had non-dysplastic IM at baseline. At one year after RFA, complete eradication of dysplasia was noted in four patients with low-grade dysplasia (100%). Gastric IM persisted in all patients with baseline metaplasia but the severity of IM improved in 6 (75%) patients. Endoscopic RFA was safe with minimal complications encountered. CONCLUSIONS: RFA successfully eradicated low-grade dysplasia of the stomach. Gastric IM however persisted after RFA but most patients had evidence of histological improvement on follow up.


Assuntos
Ablação por Cateter/métodos , Gastroscopia/métodos , Gastropatias/cirurgia , Estômago/cirurgia , Idoso , Idoso de 80 Anos ou mais , Ablação por Cateter/efeitos adversos , Estudos de Viabilidade , Feminino , Gastroscopia/efeitos adversos , Humanos , Masculino , Metaplasia , Pessoa de Meia-Idade , Projetos Piloto , Complicações Pós-Operatórias/etiologia , Estudos Prospectivos , Fatores de Risco , Estômago/patologia , Gastropatias/patologia , Fatores de Tempo , Resultado do Tratamento
20.
Asia Pac J Clin Oncol ; 10(4): 297-307, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25227602

RESUMO

Human epidermal growth factor receptor 2 (HER2) testing in gastric and gastroesophageal junction cancer is an evolving area in clinical practice that has particular relevance to Asia-Pacific countries, which face a high incidence of these diseases. A growing body of evidence demonstrates that HER2-targeted therapy improves survival for patients with HER2-positive advanced disease, and drives the need for high-quality testing procedures to identify patients who will respond to treatment. However, various factors challenge day-to-day testing of gastric specimens in these countries, to a degree greater than that observed for breast specimens. Recommendations for HER2 testing of gastric cancer specimens were published as a result of the Trastuzumab for Gastric Cancer (ToGA) trial. The guidelines proposed in this manuscript build on these recommendations and emphasize local testing environments, particularly in Asia-Pacific countries. A multidisciplinary task force comprising experts from Asia-Pacific who actively work and provide education in the area was convened to assess the applicability of existing recommendations in the Asia-Pacific region. The resulting recommendations reported here highlight and clarify aspects of testing that are of particular relevance to the region, and notably emphasize multidisciplinary collaborations to optimize HER2 testing quality.


Assuntos
Receptor ErbB-2/análise , Neoplasias Gástricas/patologia , Comitês Consultivos , Austrália , Ásia Oriental , Guias como Assunto , Humanos , Imuno-Histoquímica , Ensaios Clínicos Controlados Aleatórios como Assunto , Receptor ErbB-2/genética , Neoplasias Gástricas/genética
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