PubMed Health⌕ Search

Biomedical subjects

Simon S Cross

Publications and source records attributed to Simon S Cross.

28 records · Page 2Linked to original sources
PubMed2004

Dysregulated expression of S100A11 (calgizzarin) in prostate cancer and precursor lesions.

S100A11 is a calcium-binding protein implicated in a variety of biologic functions such as proliferation and differentiation as well as in cancer. To further understand its role in prostate cancer, we performed immunohistochemistry on a series of benign, premalignant, malignant and metastatic prostate cancer tissues in addition to prostate cancer derived cell lines. In benign prostatic hyperplasia (n=30) and benign tissue adjacent to adenocarcinoma (n=54), S100A11 expression was significantly higher in basal cells compared with in luminal cells (P <0.001). A complete absence of staining was seen in 4/14 (29%) lesions of prostatic intraepithelial neoplasia. The majority of tumors, 39/54 (72%), showed significant overexpression of S100A11 compared with the luminal cells of adjacent benign epithelium (P <0.001), whereas 14/54 (26%) of cases showed an absence of staining. All 4 cases of metastatic cancer showed intense to moderate expression. There was a significant association between S100A11 expression and high pathologic stage (pT3b) versus lower stages (pT2a-3a; P=0.027), but not with tumor Gleason score or prostate-specific antigen levels. LNCaP, PC3, and Du145 cancer cell lines showed intense to moderate S100A11 expression by immunochemistry, which was confirmed by Western blotting and reverse-transcription polymerase chain reaction. A survey of 14 other types of normal tissues arranged on a tissue microarray showed that S100A11 is widely expressed amongst epithelia. Our finding of frequent dysregulated expression of S100A11 in cancer and precursor lesions, together with an association with high histological stage, suggests that S100A11 may be involved in prostate cancer development and progression.

Adenocarcinoma↗
PubMed2004

A prospective evaluation of high-magnification chromoscopic colonoscopy in predicting completeness of EMR.

BACKGROUND: EMR is used to treat flat and sessile lesions in the colon. The aim of this study was to prospectively assess the efficacy of high-magnification chromoscopic colonoscopy in predicting complete resection margins after EMR. METHODS: A total of 1250 patients underwent colonoscopy by using a magnifying colonoscope. Chromoscopy with indigo carmine and crystal violet dye solutions was used to assess mucosal pit patterns. EMR was performed by using the saline solution inject-and-cut technique. After EMR, resection margins were inspected by using high magnification, and completeness of excision was predicted from the surface pit pattern. This was compared with completeness of excision as determined histopathologically. RESULTS: A total of 684 lesions were treated by EMR (62 piecemeal) in 602 patients. The sensitivity of high-magnification chromoscopic colonoscopy for predicting remnant tissue in the lateral margins and the deep margins were, respectively, 79% and 80%. Specificity for both margins was 97%. The overall accuracy of high-magnification chromoscopic colonoscopy in predicting incomplete resection after EMR in the lateral axis and the deep axis was, respectively, 93% and 95%, where the true respective fractions of incomplete resections were 17% and 10%. Of the single en bloc EMRs performed, 77 (12%) had histopathologic evidence of incomplete resection in either axis, compared with 60 (97%) of the 62 piecemeal resections. Piecemeal resection was more likely to result in incomplete resection compared with en bloc EMR (p < 0.001). Complete resection by EMR was more likely if the lesion was sessile instead of flat (p < 0.001). CONCLUSIONS: High-magnification chromoscopic colonoscopy as an in vivo modality for prediction of remnant tissue after EMR has a high overall accuracy, but further studies assessing long-term outcome and cost-effectiveness compared with conventional colonoscopic techniques are required.

Adenoma↗
PubMed2003

Distinct patterns of microsatellite instability are seen in tumours of the urinary tract.

To date, two forms of microsatellite instability (MSI) have been described in human cancer. MSI typical of hereditary nonpolyposis colon cancer (HNPCC), is due to deficient DNA mismatch repair (MMR) and is defined with mono- and dinucleotide repeat microsatellites. A second variety of instability is best seen at selective tetranucleotide repeats (EMAST; elevated microsatellite alterations at select tetranucleotides). While MSI occurs infrequently in bladder cancers, EMAST is common. Sporadic tumours with the largest proportion showing MSI are those found most frequently in HNPCC kindreds. While bladder cancer is not frequently seen in HNPCC, upper urinary tract tumours (UTTs) are. Having previously found a low frequency of MSI in bladder cancer, we sought to determine the relative levels of MSI and EMAST in transitional cell carcinoma (TCC) of the upper and lower urinary tracts. Microsatellite analysis was performed at 10 mono- and dinucleotide and eight tetranucleotide loci, in 89 bladder and 71 UTT TCC. Contrasting patterns of instability were seen in urinary tumours. In bladder cancer, MSI was rare and EMAST was common. The presence of EMAST was not related to tumour grade, stage, subsequent outcome or immunohistochemical expression of the MMR proteins. In UTT, while MSI occurred frequently, EMAST was seen less frequently than in bladder cancer. When TCC of the upper and lower urinary tracts are compared, MSI-H is more frequent in UTT and EMAST more frequent in bladder cancer. Our findings show that, as for colorectal cancer, the pattern of MSI varies with location in the urinary tract. In addition, we have confirmed that MSI and EMAST are discrete forms of MSI, and that the presence of EMAST does not affect tumour phenotype.

Adaptor Proteins, Signal Transducing↗
PubMed2003

Symptomatic giardiasis without diarrhea: further evidence to support the routine duodenal biopsy?

BACKGROUND: Worldwide, Giardia lamblia is the most common protozoan isolated from the GI tract. Patients with symptoms caused by giardiasis typically present with diarrhea, the absence of which may result in a low clinical index of suspicion for the diagnosis. METHODS: A series of 6 patients with giardiasis presenting without diarrhea is reported. Five presented with atypical GI symptoms. In all 6 cases, diarrhea was absent. Upper GI pathology was suspected by the investigating clinician and EGD was therefore arranged. OBSERVATIONS: Five of the 6 patients improved with appropriate antibiotic treatment. CONCLUSION: This series of cases demonstrates the importance of considering G lamblia as a cause for GI symptoms even in the absence of diarrhea. Routine procurement of duodenal biopsy specimens is valuable for recognition of atypical presentations of patients with G lamblia and avoiding delays in diagnosis.

Adult↗
PubMed2003

A prospective clinicopathological and endoscopic evaluation of flat and depressed colorectal lesions in the United Kingdom.

OBJECTIVES: Flat and depressed colorectal lesions are now reported in Western populations. The malignant potential, anatomical distribution, and other clinicopathological features have not been established in this group. This study aimed to assess prospectively the prevalence, clinicopathological, and endoscopic features of flat and depressed colorectal lesions in the United Kingdom. METHODS: A single endoscopist performed colonoscopy on 850 consecutive patients presenting for routine colonoscopy. All endoscopies were performed using a high magnification colonoscope with chromoscopy to facilitate detection of flat and depressed colorectal lesions. RESULTS: A total of 458 flat lesions were identified. Of these, 173 (38%) were hyperplastic and 285 (62%) adenomatous or beyond. Of the 173 hyperplastic flat lesions, 162 (94%) were located in the recto-sigmoid region. Of the 267 adenomas, 66 (25%) had areas of high grade dysplasia (HGD), with 54/66 (82%) being present in the right colon. Flat lesions <8 mm in diameter was more likely to contain HGD than those <8 mm (p<0.001). Nine of the 10 (90%) flat invasive adenoacarcinomas were in the right colon and all had a depressed morphological component. In contrast, HGD was observed in 58/466 (12%) of protuberant (sessile/pedunculated) adenomas of which 95% (55/58) were located in the left colon. In addition, HGD was present in 17% of all sessile adenomas versus 44.6% of flat lesions >8 mm in diameter (p=0.001). Of the 14 protuberant carcinomas, 13/14 (93%) were in the left colon. Synchronous lesions were found in 96/816 (12%) of cases. Of the 816 patients with two or more left-sided protuberant adenomas <8 mm (with or without HGD), 89 (11%) had one or more flat lesions in the right colon with HGD. CONCLUSIONS: Flat adenomas and carcinomas have a high malignant potential compared to protuberant lesions and have a propensity for developing in the right hemi-colon. Total colonoscopy is required to detect such lesions, as only 18% of flat lesions would be in reach of the flexible sigmoidoscope.

Adult↗
PubMedDate not supplied

Angiogenesis induction and regression in human surgical wounds.

Angiogenesis in human wound healing is not well characterized, with only sparse information available regarding the maturation and fate of vessels formed as a consequence of human tissue repair. Therefore, this study aimed to establish the temporal profile of angiogenesis in human dermal wounds. Punch biopsies were obtained under local anesthesia from 45 patients following breast surgery. Scars were predominantly between 2 and 52 weeks after surgery but in five patients were > 52 weeks. Control samples were taken from breast skin peroperatively (n = 24). Quantification of vascular density was performed using the Chalkley grid, following antibody staining for platelet endothelial cell adhesion molecule. Vascular patterns, wound cellularity and morphology were also determined. Cumulative microvessel density was increased in all samples when compared to controls (p < 0.05). This was greatest 2 to 24 weeks following surgery 17 (15-21) median (range), decreased thereafter, but remained elevated compared to controls even in the mature scars > 52 weeks. Control tissue showed an ordered morphological arrangement of dermal structures, collagen, and elastic fibers. However, wounding resulted in marked structural distortion for up to 15 weeks. In conclusion, this study shows for the first time the prolonged persistence of both microvessels and cellularity (fibroblastic cells), in addition to structural distortion in human dermal wounds, which is in contrast to previous in vitro and in vivo studies.

Adult↗
PubMedDate not supplied

Matrix metalloproteinase activity and immunohistochemical profile of matrix metalloproteinase-2 and -9 and tissue inhibitor of metalloproteinase-1 during human dermal wound healing.

Proteolytic activity is required for the turnover of the extracellular matrix during wound healing. Matrix metalloproteinases can collectively cleave all components of the extracellular matrix, with the endogenous tissue inhibitor of metalloproteinase-1 regulating their activity. Breast tissue taken at varying postoperative times (n= 92) or during surgery (controls, n= 17), was used to investigate the temporal and spatial activity of matrix metalloproteinase-2 and -9 and tissue inhibitor of metalloproteinase-1 during human wound healing. Matrix metalloproteinase activity, determined using a quenched fluorescence substrate assay, increased during early healing (3-8 weeks) compared to controls, and then decreased between 24 and 36 weeks after surgery (p < 0.05 until 24 weeks, Mann-Whitney U-test). Immunohistochemistry scores for matrix metalloproteinase-9 expression were significantly elevated compared to controls in scar endothelial cells and fibroblasts from 2 until 12 and 20 weeks, respectively. Matrix metalloproteinase-2 staining was observed exclusively in fibroblasts, reaching maximum levels 8-12 weeks after surgery, decreasing by 1.5 years but remaining significantly increased. Tissue inhibitor of metalloproteinase-1 staining was relatively sparse but was significantly increased until 8 weeks after surgery. These results show that matrix metalloproteinases are present at elevated levels during early wound healing, when angiogenesis occurs, and suggest that matrix metalloproteinase-9 may play a significant role. The later expression of matrix metalloproteinase-2 and -9 in fibroblasts suggests a role in extracellular matrix remodeling.

Adult↗