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1.
Front Cell Dev Biol ; 8: 564648, 2020.
Article in English | MEDLINE | ID: mdl-33324632

ABSTRACT

Colorectal cancer (CRC) is one of the most widely diagnosed cancers worldwide. It has been shown that the body-mass index (BMI) of the patients could influence the tumor microenvironment, treatment response, and overall survival rates. Nevertheless, the mechanism on how BMI affects the tumorigenesis process, particularly the tumor microenvironment is still elusive. Herein, we postulate that extracellular vesicles (EVs) from CRC patients and non-CRC volunteers with different BMI could affect immune cells differently, in CD8 T cells particularly. We isolated the EVs from the archived serum of CRC patients with high and low BMI, as well as healthy controls with similar BMI status. The EVs were further characterized via electron microscopy, western blot and dynamic light scattering. Then, functional analysis was performed on CD8 T cells including apoptosis, cell proliferation, gene expression profiling and cytokine release upon co-incubation with the different EVs. Our results suggest that CRC-derived EVs were able to regulate the CD8 T cells. In some assays, low BMI EVs were functionally different than high BMI EVs. This study highlights the possible difference in the regulatory mechanism of cancer patients-derived EVs, especially on CD8 T cells.

2.
Biomolecules ; 10(5)2020 05 05.
Article in English | MEDLINE | ID: mdl-32380793

ABSTRACT

The methylome of open chromatins was investigated in colorectal cancer (CRC) to explore cancer-specific methylation and potential biomarkers. Epigenome-wide methylome of open chromatins was studied in colorectal cancer tissues using the Infinium DNA MethylationEPIC assay. Differentially methylated regions were identified using the ChAMP Bioconductor. Our stringent analysis led to the discovery of 2187 significant differentially methylated open chromatins in CRCs. More hypomethylated probes were observed and the trend was similar across all chromosomes. The majority of hyper- and hypomethylated probes in open chromatin were in chromosome 1. Our unsupervised hierarchical clustering analysis showed that 40 significant differentially methylated open chromatins were able to segregate CRC from normal colonic tissues. Receiver operating characteristic analyses from the top 40 probes revealed several significant, highly discriminative, specific and sensitive probes such as OPLAH cg26256223, EYA4 cg01328892, and CCNA1 cg11513637, among others. OPLAH cg26256223 hypermethylation is associated with reduced gene expression in the CRC. This study reports many open chromatin loci with novel differential methylation statuses, some of which with the potential as candidate markers for diagnostic purposes.


Subject(s)
Chromatin/genetics , Colorectal Neoplasms/genetics , Epigenome , Cyclin A1/genetics , Cyclin A1/metabolism , DNA Methylation , Gene Expression Regulation, Neoplastic , Humans , Trans-Activators/genetics , Trans-Activators/metabolism
3.
BMC Public Health ; 19(Suppl 4): 550, 2019 Jun 13.
Article in English | MEDLINE | ID: mdl-31196184

ABSTRACT

BACKGROUND: Inflammatory bowel disease (IBD) was once considered as a Western disease. However, recent epidemiological data showed an emerging trend of IBD cases in the Eastern Asia countries. Clinico-epidemiological data of IBD in Malaysia is scarce. This study aimed to address this issue. METHODS: Retrospective analysis of ulcerative colitis (UC) and Crohn's disease (CD), diagnosed from January 1980 till June 2018 was conducted at our centre. RESULTS: A total of 413 IBD patients (281 UC, 132 CD) were identified. Mean crude incidence of IBD has increased steadily over the first three decades: 0.36 (1980-1989), 0.48 (1990-1999) and 0.63 per 100,000 person-years (2000-2009). In the 2010 to 2018 period, the mean crude incidence has doubled to 1.46 per 100,000 person-years. There was a significant rise in the incidence of CD, as depicted by reducing UC:CD ratio: 5:1 (1980-1989), 5:1 (1990-1999), 1.9:1 (2000-2009) and 1.7:1 (2010-2018). The prevalence rate of IBD, UC and CD, respectively were 23.0, 15.67 and 7.36 per 100,000 persons. Of all IBD patients, 61.5% (n = 254) were males. When stratified according to ethnic group, the highest prevalence of IBD was among the Indians: 73.4 per 100,000 persons, followed by Malays: 24.8 per 100,000 persons and Chinese: 14.6 per 100,000 persons. The mean age of diagnosis was 41.2 years for UC and 27.4 years for CD. Majority were non-smokers (UC: 76.9%, CD: 70.5%). The diseases were classified as follows: UC; proctitis (9.2%), left-sided colitis (50.2%) and extensive colitis (40.6%), CD; isolated ileal (22.7%), colonic (28.8%), ileocolonic (47.7%) and upper gastrointestinal (0.8%). 12.9% of CD patients had concurrent perianal disease. Extra intestinal manifestations were observed more in CD (53.8%) as compared to UC (12%). Dysplasia and malignancy, on the other hand, occurred more in UC (4.3%, n = 12) than in CD (0.8%, n = 1). Over one quarter (27.3%) of CD patients and 3.6% of UC patients received biologic therapy. CONCLUSION: The incidence of IBD is rising in Malaysia, especially in the last one decade. This might be associated with the urbanization and changing diets. Public and clinicians' awareness of this emerging disease in Malaysia is important for the timely detection and management.


Subject(s)
Colitis, Ulcerative/epidemiology , Crohn Disease/epidemiology , Inflammatory Bowel Diseases/epidemiology , Adolescent , Adult , Aged , Female , Humans , Incidence , Malaysia/epidemiology , Male , Middle Aged , Prevalence , Retrospective Studies , Urbanization , Young Adult
4.
Surg Laparosc Endosc Percutan Tech ; 27(5): 341-345, 2017 Oct.
Article in English | MEDLINE | ID: mdl-28902038

ABSTRACT

BACKGROUND: Surgical smoke containing potentially carcinogenic and harmful materials is an inevitable consequence of surgical energy devices, and constitutes a substantial occupational hazard in the operating room. This study aimed to evaluate the efficacy of a built-in-filter trocar in eliminating hazardous surgical smoke during laparoscopic and robotic rectal surgery. METHODS: Ten patients who underwent rectal cancer resection were enrolled. Five patients underwent surgery utilizing a nonfiltered trocar, and the remaining 5 utilized a built-in-filter trocar. Gas samples were aspirated from the peritoneal cavity over 30 minutes of electrocauterization and collected in a Tedlar bag. Concentrations of surgical smoke were measured using ultraperformance liquid chromatography and gas chromatography. RESULTS: Eleven hazardous chemical compounds (benzene, toluene, ethylbenzene, xylene, styrene, formaldehyde, acetaldehyde, propionaldehyde, butyraldehyde, isovaleraldehyde, and valeraldehyde) were identified in the surgical smoke. With the built-in-filter trocar, removal rates of 69% for benzene (P=0.028), 72% for toluene (P=0.009), 67% for butyraldehyde (P=0.047), 46% for ethylbenzene (P=0.092), 44% for xylene (P=0.086), 35% for styrene (P=0.106), 39% for formaldehyde (P=0.346), and 33% for propionaldehyde (P=0.316) were achieved. CONCLUSIONS: This study confirmed the presence of harmful materials in surgical smoke. Evacuation of surgical smoke through a disposable built-in-filter trocar is a simple and effective way in reducing volatile organic compounds concentrations.


Subject(s)
Filtration/instrumentation , Hazardous Substances/isolation & purification , Laparoscopy/instrumentation , Rectal Neoplasms/surgery , Smoke/prevention & control , Surgical Instruments , Case-Control Studies , Chromatography , Equipment Design , Feasibility Studies , Female , Humans , Male , Mass Spectrometry , Micropore Filters , Middle Aged , Pilot Projects , Robotic Surgical Procedures/instrumentation , Smoke/analysis , Spectrophotometry
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