ABSTRACT
BACKGROUND: The detection of microRNA (miRNA) dysregulation in stool is a novel approach for the diagnosis of colorectal carcinoma (CRC). The aim of this study is to investigate the use of miR-221 and miR-18a in stool samples as non-invasive biomarkers for CRC diagnosis. METHODS: A miRNA expression array containing 667 miRNAs was performed to identify miRNA dysregulation in CRC tissues. We focused on miR-221 and miR-18a, two significantly upregulated miRNAs which were subsequently verified in 40 pairs of CRC tissues and 595 stool samples (198 CRCs, 199 polyps and 198 normal controls). RESULTS: miR-221 and miR-18a were upregulated in the miRNA expression array. miR-221 and miR-18a levels were also significantly higher in 40 CRC tumours compared with their respective adjacent normal tissues. In stool samples, miR-221 and miR-18a showed a significant increasing trend from normal controls to late stages of CRC (P<0.0001). The levels of stool miR-221 and miR-18a were both significantly higher in subjects with stages I+II (miR-221: P<0.0001, miR-18a: P<0.0001) and stages III+IV of CRC (miR-221: P=0.0004, miR-18a: P<0.0001) compared with normal controls. The AUC of stool miR-221 and miR-18a were 0.73 and 0.67 for CRC patients as compared with normal controls, respectively. No significant differences in stool miR-221 and miR-18a levels were found between patients with proximal and distal CRCs. The use of antibiotics did not influence stool miRNA-221 and miRNA-18a levels. CONCLUSIONS: Stool-based miR-221 can be used as a non-invasive biomarker for the detection of CRC.
Subject(s)
Biomarkers, Tumor/genetics , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/genetics , Feces/chemistry , MicroRNAs/genetics , Aged , Case-Control Studies , Female , Follow-Up Studies , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Humans , Male , Middle Aged , Oligonucleotide Array Sequence Analysis , Prognosis , ROC CurveABSTRACT
The NF-kappaB signalling pathway plays important roles in liver organogenesis and carcinogenesis. Mouse embryos deficient in IKKbeta die in mid-gestation, due to excessive apoptosis of hepatoblasts. Although activation of the NF-kappaB signalling pathway has been demonstrated in human hepatocellular carcinoma, the role of NF-kappaB is controversial. Here, we have generated transgenic mice in which a constitutively active form of IKKbeta was expressed in a hepatocyte-specific manner. Using electrophoretic mobility shift assay, we documented increased NF-kappaB activities and up-regulated levels of NF-kappaB downstream target genes, Bcl-xL and STAT5, in the transgenic mouse livers. These results confirmed that the NF-kappaB pathway was activated in the livers of the transgenic mice. However, there was no significant difference in tumour formation between transgenic and wild-type mice up to an age of 50 weeks. When we treated the transgenic mice with the chemical carcinogen diethylnitrosamine (DEN), we observed no significant differences in the incidence and size of liver tumours formed in these mice with and without DEN treatment at 35 weeks of age, suggesting that the activated NF-kappaB pathway in the livers of the transgenic mice did not enhance hepatocarcinogenesis. Interestingly, some of the transient transgenic embryos (E12.5) had abnormal excessive accumulation of nucleated red blood cells in their developing livers. In summary, NF-kappaB activation in hepatocytes did not significantly affect chemical hepatocarcinogenesis. In addition, the TTR/IKKCA transgenic mice may serve as a useful model for studying the role of NF-kappaB activation in hepatocarcinogenesis as well as inflammatory and metabolic diseases.
Subject(s)
Carcinoma, Hepatocellular/metabolism , Hepatocytes/metabolism , I-kappa B Kinase/genetics , Liver Neoplasms, Experimental/metabolism , NF-kappa B/metabolism , Animals , Blotting, Western/methods , Carcinoma, Hepatocellular/chemically induced , Cell Line, Tumor , Diethylnitrosamine , Electrophoretic Mobility Shift Assay , I-kappa B Kinase/metabolism , Immunohistochemistry , Liver/embryology , Liver Neoplasms, Experimental/chemically induced , Male , Mice , Mice, Transgenic , NF-kappa B/analysis , Transfection/methodsABSTRACT
We conducted a survey on staff perceptions of what the educational needs would be for an infection surveillance and control program in patient care practices in 10 hospitals in Hong Kong. Seven hundred twenty nurses were interviewed and were requested to select their needs from six topics: isolation procedures, disinfection of environment and instruments, surgical wound care, urinary catheter care, prevention of hospital-acquired pneumonia, and prevention of infusion therapy sepsis. According to their pattern of needs, the clinical units could be divided into three groups. Staff members in the "medically oriented units," consisting of the medical, geriatric, obstetric, and intensive care units, indicated that their greatest needs were in the areas of isolation procedures and disinfection of environment and instruments, whereas nurses in the "surgically oriented units," consisting of surgical, orthopedic, and gynecologic units, indicated that surgical wound care was the area where education was most needed. The pattern in the third group, the pediatric units, was similar to that of medical units in indicating isolation procedures and disinfection of environment and instruments as the greatest needs but differed in having a higher score for prevention of hospital-acquired pneumonias and a lower score for surgical wound care. An effective educational program should take these needs into consideration. We discuss the application of the survey findings in planning in-service education in infection control.
