The actin-bundling protein Fascin is overexpressed in inflammatory bowel disease and may be important in tissue repair

<b>Background</b> Fascin is associated with increased cell motility in colorectal tumours but is absent from the normal colonic epithelium. We examined the expression of fascin in inflammatory bowel disease (IBD) and its location at regions undergoing restitution and regeneration. Tissue repair is essential for disease remission and we sought to determine the effects of therapeutic modalities on fascin expression and function using an in vitro model.<p></p> <b>Methods</b> Immunohistochemistry was performed on colonic tissue from IBD patients to determine changes in fascin expression and distribution. A human colorectal epithelial cell line was treated with 5-aminosalicylate (a common treatment for IBD), or sodium butyrate to determine the effect on fascin expression and cell motility.<p></p> <b>Results</b> Fascin overexpression was observed in both ulcerative colitis and Crohn's colitis and expression correlated with disease severity. Immunoreactivity was more intense and widespread in Crohn's compared to ulcerative colitis. Interestingly, highly expressing foci were consistently observed at the edges of ulcers where flattened, motile epithelial cells are actively involved in restitution, and also in areas of mucosal regeneration. 5-aminosalicylate reduced fascin expression in colorectal epithelial cells and inhibited their motility. Conversely, sodium butyrate increased fascin expression and stimulated cell motility in the same cells.<p></p> <b>Conclusions</b> Our data shows that fascin is overexpressed in inflammatory bowel disease and its location is indicative of a role in tissue repair. Our in vitro studies show that different therapeutic modalities may have converse effects on fascin expression and may have significant consequences for disease remission and the clinical management of IBD

The actin-bundling protein fascin is overexpressed in colorectal adenomas and promotes motility in adenoma cells in vitro

Background: Fascin is overexpressed in many cancers, including colorectal, but its role in the malignant transformation of benign colorectal adenomas is unclear. Methods: Immunohistochemical analysis of fascin expression was carried out in resected human colorectal adenoma specimens. The effects of forced overexpression of fascin on adenoma cell motility were also analysed. Results: We show fascin overexpression in adenomas increasing with tumour size, histological type, and degree of dysplasia and increased cell motility in adenoma cell lines following fascin transfection. Conclusion: These data suggest an important role for fascin in the malignant progression of colorectal tumours

The very bright SCUBA galaxy count: looking for SCUBA galaxies with the Mexican Hat Wavelet

We present the results of a search for bright high-redshift galaxies in two large SCUBA scan-maps of Galactic regions. A Mexican Hat Wavelet technique was used to locate point sources in these maps, which suffer high foreground contamination as well as typical scan-map noise signatures. A catalogue of point source objects was selected and observed again in the submillimetre continuum, and in HCO+ (3->2) at zero redshift to rule out Galactic sources. No extragalactic sources were found. Simulations show that the survey was sensitive to sources with fluxes > 50 mJy, depending on the local background. These simulations result in upper limits on the 850-micron counts of SCUBA galaxies of 53 per square degree at 50 mJy and 2.9 per square degree at 100 mJy.Comment: Accepted by MNRA

Factors influencing patient satisfaction with dental appearance and treatments they desire to improve aesthetics

Background: We assessed factors influencing patients’ satisfaction with their dental appearance and the treatments they desired to improve dental aesthetics. Methods: A cross-sectional study was performed out among 235 adult patients who visited the Hospital Universiti Sains Malaysia dental clinic. A structured, interviewer-guided questionnaire was used to identify patient satisfaction with their general dental appearance, cosmetic elements and desired treatments. Results: The 235 patients consisted of 70 males (29.8%) and 165 females (70.2%), of mean age 31.5 years (SD 13.0). Of these patients, 124 (52.8%) were not satisfied with their general dental appearance. In addition, 132 patients (56.2%) were not happy with the color of their teeth, 76 (32.3%), regarded their teeth were poorly aligned, 62 (26.4%), as crowded and 56 (23.4%) protruded. Dissatisfaction with tooth color was significantly higher in female than in male patients (odds ratio [OR] of 1.99 (95% confidence interval [CI] 1.13-3.50). Tooth whitening was the treatment most desired by patients (48.1%). Results of multiple logistic regression analysis showed that patient dissatisfaction with general dental appearance was significantly associated with female gender (OR = 2.18; 95% CI: 1.18-4.03), unhappiness with tooth color (OR = 3.05; 95% CI: 1.74-5.34) and the opinion that their teeth protruded (OR = 2.91, 95% CI: 1.44-5.91)

Abrogation of the radiation-induced G2 checkpoint by the staurosporine derivative UCN-01 is associated with radiosensitisation in a subset of colorectal tumour cell lines

Ionising radiation is commonly used in the treatment of colorectal cancer. Tumour cells with mutant p53 undergo cell cycle arrest at G2/M after ionising radiation and evidence suggests that abrogation of this G2 arrest can lead to a premature, aberrant mitosis, thus enhancing ionising radiation-induced cell killing. The G2 checkpoint inhibitor UCN-01 was thus investigated to determine whether it would abrogate the G2 checkpoint induced by 5 Gy ionising radiation in a range of colorectal tumour cell lines. Data presented show that, at doses that are alone non-toxic to the cells, UCN-01 inhibits the ionising radiation-induced G2 checkpoint in five colorectal tumour cell lines with mutant p53. The ability of UCN-01 to sensitise cells to ionising radiation-induced growth inhibition and apoptosis was also investigated and UCN-01 was found to radiosensitise two out of five cell lines. These results were confirmed by long-term colony forming efficiency studies. These results demonstrate that abrogation of the ionising radiation-induced G2 checkpoint is not necessarily associated with sensitisation to ionising radiation, however, some colorectal tumour cell lines can be radiosensitised by UCN-01. Although the mechanism of radiosensitisation is not clear, this may still be an important treatment strategy

IGFBP-rP1, a potential molecule associated with colon cancer differentiation

<p>Abstract</p> <p>Background</p> <p>In our previous studies, we have demonstrated that insulin-like growth factor binding protein-related protein1 (IGFBP-rP1) played its potential tumor suppressor role in colon cancer cells through apoptosis and senescence induction. In this study, we will further uncover the role of IGFBP-rP1 in colon cancer differentiation and a possible mechanism by revealing responsible genes.</p> <p>Results</p> <p>In normal colon epithelium, immunohistochemistry staining detected a gradient IGFBP-rP1 expression along the axis of the crypt. IGFBP-rP1 strongly expressed in the differentiated cells at the surface of the colon epithelium, while weakly expressed at the crypt base. In colon cancer tissues, the expression of IGFBP-rP1 correlated positively with the differentiation status. IGFBP-rP1 strongly expressed in low grade colorectal carcinoma and weakly expressed in high grade colorectal carcinoma. In vitro, transfection of PcDNA3.1(IGFBP-rP1) into RKO, SW620 and CW2 cells induced a more pronounced anterior-posterior polarity morphology, accompanied by upregulation with alkaline phosphatase (AKP) activity. Upregulation of carcino-embryonic antigen (CEA) was also observed in SW620 and CW2 transfectants. The addition of IGFBP-rP1 protein into the medium could mimic most but not all effects of IGFBP-rP1 cDNA transfection. Seventy-eight reproducibly differentially expressed genes were detected in PcDNA3.1(IGFBP-rP1)-RKO transfectants, using Affymetrix 133 plus 2.0 expression chip platform. Directed Acyclic Graph (DAG) of the enriched GO categories demonstrated that differential expression of the enzyme regulator activity genes together with cytoskeleton and actin binding genes were significant. IGFBP-rP1 could upreguate Transgelin (TAGLN), downregulate SRY (sex determining region Y)-box 9(campomelic dysplasia, autosomal sex-reversal) (SOX9), insulin receptor substrate 1(IRS1), cyclin-dependent kinase inhibitor 2B (p15, inhibits CDK4) (CDKN2B), amphiregulin(schwannoma-derived growth factor) (AREG) and immediate early response 5-like(IER5L) in RKO, SW620 and CW2 colon cancer cells, verified by Real time Reverse Transcription Polymerase Chain Reaction (rtRT-PCR). During sodium butyrate-induced Caco2 cell differentiation, IGFBP-rP1 was upregulated and the expression showed significant correlation with the AKP activity. The downregulation of IRS1 and SOX9 were also induced by sodium butyrate.</p> <p>Conclusion</p> <p>IGFBP-rP1 was a potential key molecule associated with colon cancer differentiation. Downregulation of IRS1 and SOX9 may the possible key downstream genes involved in the process.</p

Does the gender of the subject affect perceived smile aesthetics when varying the dimensions of maxillary lateral incisors?

Objective To assess whether subject gender influences aesthetic opinion when altering the width of maxillary lateral incisors. Method Photographs of a male and a female smile, displaying only the lips and teeth, were digitally altered to produce images where the maxillary lateral incisor was proportioned 52%, 57%, 62%, 67%, 72% and 77% in relation to the width of the maxillary central incisor. The image was then made symmetrical. One hundred participants (50 male and 50 female) were asked to rank each set of photographs from 'most' to 'least attractive'. Result The 57% lateral incisor was considered the 'most attractive' with the 77% lateral incisor the 'least attractive' however no statistically significant difference existed with relation to subject or rater gender. Conclusion Neither the 'golden proportion' nor the 'Recurrent Aesthetic Dental' ('RED') proportion was deemed the most attractive. As subject gender did not have a significant effect, dentists should work to create aesthetic results on an individual basis, operating within a so-called 'golden range'

Expression of CDX2 in normal and neoplastic human colon tissue and during differentiation of an in vitro model system

Background: The Cdx genes are expressed in the colorectal epithelium and are frequently downregulated during tumorigenesis. Overexpression of Cdx genes has been shown previously to result in cellular differentiation. Aim: To study expression of CDX2 in normal and neoplastic human colon using a newly isolated monoclonal antibody. To define expression of CDX1 and CDX2 in an in vitro model system of colorectal tumour progression and to ascertain whether these are subject to regulation during differentiation. Methods: Normal and neoplastic human colon was immunostained for CDX2. CDX1 and CDX2 expression was assayed in cell lines derived from premalignant colonic adenomas by western blotting. Differentiation was induced by sodium butyrate treatment or post confluent growth, and changes in CDX expression compared with carcinoma cell lines with low levels of CDX expression. Results: CDX2 protein displayed no gradient of expression within the colonic crypt. Cell lines derived from adenomas, with high levels of CDX1 and CDX2, showed no regulation of these proteins when induced to differentiate by butyrate or confluency. CDX expression in these cell lines was independent of their APC or Ras status. CDX1 and CDX2 were expressed at very low levels in some carcinoma cell lines and were modestly upregulated on differentiation but were not restored to levels seen in adenoma cells. Conclusion: The lack of significant regulation on cellular differentiation and the absence of a detectable gradient in the crypt implies that CDX2 may confer tissue specificity but may not play the previously suggested role in crypt patterning