COL11A1 in FAP polyps and in sporadic colorectal tumors

BACKGROUND: We previously reported that the α-1 chain of type 11 collagen (COL11A1), not normally expressed in the colon, was up-regulated in stromal fibroblasts in most sporadic colorectal carcinomas. Patients with germline mutations in the APC gene show, besides colonic polyposis, symptoms of stromal fibroblast involvement, which could be related to COL11A1 expression. Most colorectal carcinomas are suggested to be a result of an activated Wnt- pathway, most often involving an inactivation of the APC gene or activation of β-catenin. METHODS: We used normal and polyp tissue samples from one FAP patient and a set of 37 sporadic colorectal carcinomas to find out if the up-regulation of COL11A1 was associated with an active APC/β-catenin pathway. RESULTS: In this study we found a statistically significant difference in COL11A1 expression between normal tissue and adenomas from one FAP patient, and all adenomas gave evidence for an active APC/β-catenin pathway. An active Wnt pathway has been suggested to involve stromal expression of WISP-1. We found a strong correlation between WISP-1 and COL11A1 expression in sporadic carcinomas. CONCLUSIONS: Our results suggest that expression of COL11A1 in colorectal tumors could be associated with the APC/β-catenin pathway in FAP and sporadic colorectal cancer

Vitamin C transporter gene (SLC23A1 and SLC23A2) polymorphisms, plasma vitamin C levels, and gastric cancer risk in the EPIC cohort

Vitamin C is known to protect mucosal tissues from oxidative stress and inhibit nitrosamine formation in the stomach. High consumption of fruits, particularly citrus, and higher circulating vitamin C concentrations may be inversely associated with gastric cancer (GC) risk. We investigated 20 polymorphisms in vitamin C transporter genes SCL23A1 and SCL23A2 and GC risk in 365 cases and 1,284 controls nested within the European Prospective Investigation into Cancer and Nutrition cohort. We also evaluated the association between these polymorphisms and baseline plasma vitamin C levels in a subset of participants. Four SNPs were predictors of plasma vitamin C levels (SLC23A1 rs11950646 and rs33972313; SLC23A2 rs6053005 and rs6133175) in multivariable linear regression models. One SNP (SLC23A2 rs6116569) was associated with GC risk, in particular non-cardia GC (OR = 1.63, 95 % CI = 1.11-2.39, based on 178 non-cardia cases), but this association was attenuated when plasma vitamin C was included in the logistic regression model. Haplotype analysis of SLC23A1 yielded no associations with GC. In SLC23A2, one haplotype was associated with both overall and non-cardia GC, another haplotype was associated with GC overall, and a third was associated with intestinal-type GC. Common variants in SLC23A1 and SLC23A2 may influence plasma vitamin C concentration independent of dietary intake, and variation in SLC23A2 may influence GC risk. Additional prospective studies in large populations and consortia are recommended. Investigation of variation in vitamin C transporter genes may shed light on the preventative properties of vitamin C in gastric carcinogenesis

The enterocyte in small intestinal adaption : an experimental and clinicopathological study with special reference to the ultrastructure of the brush border

The small intestine mucosa is known to be able to adapt itself to several kinds of both physiological and pathological conditions. The adaptive patterns of the structure of the enterocytes, particularly their apical surface (brush border), were studied in three models: (1) in rats, subjected to antrectomy or antral exclusion, combined with gastroduodenostomy and gastrojejunostomy; (2) in rats with alloxan dia­betes; (3) in children with coeliac disease; a) in its active phase; b) after long-term treatment with gluten-free diets; c) after long-term challenge with dietary gluten following treatment; d) after short-term elimination of dietary gluten. Gut mucosa from fasting or fed, normal or sham-operated rats, fasting cats, and short-statured children with no signs of gastrointestinal disease served as controls. - The specimens were prepared for light microscopy (LM), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). Quantitation of structural variables was achieved by means of LM and TEM morphometrical procedures. Differentiation of the rat enterocytes from the base to the crest of the villi was structurally reflected by doubling of their apical cell area, an increase in cell height, and a decrease of both nuclear and mitochondrial volume densities. In mature normal rat enterocytes, high-power SEM showed regularly arranged, nude microvilli in thir apical surfaces, whereas in cat and man the apical surfaces were covered by a thick glycocalyx. - Fasting for 24 hours decreased the total length of the rat small intestine and the height of the enterocytes. Antrectomy and antral exclusion with gastrojejunostomy produced an increase of the apical surfaces of the enterocytes of the seif-emptying duodenal blind loop, whereas no changes occurred after antrectomy with gastroduodeno­stomy. In the jejunum, the apical surface area was reduced both after antrectomy and antral exclusion. In the diabetic rats a slight decrease of the apical surface area, together with an elongation of both the vil­li and the crypts, was observed in the jejunum, whereas no structural changes occurred in the duodenal mucosa. Both in active coeliac disease and after long-term challenge with dietary gluten, SEM analyses showed uniformly destructed villi. The api­cal surfaces of the enterocytes were frequently convex and irregular in size and delineation (the surface of the normal enterocytes was polygo­nal and flat). Ultrastructurally, the apical surfaces were severely damaged with a distortion of the glycocalyx and with marked irregularity of the microvilli. - After gluten elimination, the surface ultrastructu­re of the enterocytes in the coeliac gut mucosa generally showed a rapid, clear-cut restoration despite a remaining severe atrophy of the villi. Successful dietary treatment (after about one year of gluten-free diet) restored the small intestine mucosa to normal as assessed both by LM and low-power SEM. In contrast, high-power SEM often disclosed per­sisting lesions of the enterocytes. Another provocation with gluten for up to 9 days in clinically healed coeliac mucosa did not significantly alter the surface ultrastructure of the enterocytes.S. 1-52: sammanfattning, s. 53-138: 5 uppsatserdigitalisering@um

Är det svårt att använda de förenklade utredningsformerna

Tänk dig att du som nyutexaminerad polis tillsammans med din kollega kallas tillen butik i stans köpcentra med anledning av ett snatteri. Den förtvivladegärningsmannen är över 18 år och erkänner gärningen på en gång ni kommerfram. Hur skulle ni lösa situationen? Kontaktar ni förundersökningsledare för attstarta en förundersökning? Eller skulle ni använda er av en förenklad utredningenligt Rättegångsbalken 23:22§?Efter snart fyra terminer på polisutbildningen och med några veckor kvar tillexamen känner vi en viss osäkerhet kring tillämpningen av förenklad utredningenligt RB 23:21§ och RB 23:22§. Vi har dessutom fått en allmän uppfattning, omatt vi inte är ensamma på utbildningen att känna denna osäkerhet kringtillämpningen av detta förfarande.Vi ställde oss frågan hur många undervisnings tillfällen vi haft i detta ämne ochkom fram till att det hitintills endast varit en lektion om förenklad utredning. Detär enligt vår mening alldeles för lite. Att veta när och hur förfarandet skaanvändas, skulle spara både tid och resurser vilket skulle leda till ett betydligteffektivare polisarbete.Användningsområdet är väldigt omfattande och användbart för poliser somtillbringar sina arbetsdagar till att lösa vardagsbrottslighet. Som exempel kanförenklad utredning användas vid: Trafikförseelser, stöld, snatteri, ringa narkotikabrott, enklare former av misshandel och så vidare. Dessa brott utgör som ni säkertförstår en väldigt stor del av vår framtida vardag.Polisens organisation och utrustning - Strategi taktik operatio

DNA Aneuploidy in Ulcerative Colitis and in Colorectal Carcinoma – A Comparative Study

DNA aneuploidy is of interest as an additive marker for carcinoma risk in ulcerative colitis. It is known that colorectal carcinomas often are aneuploid with DNA indices centered around a median value of 1.5, corresponding to triploidy, and that adenomas, if aneuploid, have DNA indices closer to 2.0, the tetraploid region. In a colonoscopic surveillance programme, colorectal mucosal biopsies from 104 patients with ulcerative colitis were examined by flow cytometry, and the DNA indices determined and compared with findings of cellular dysplasia. In 17 patients, DNA aneuploidy was diagnosed, with DNA indices ranging from 1.2 to 2.0, median 1.9. Three patients with high grade dysplasia all had DNA indices within the triploid region. These results were compared with the DNA indices from a group of 49 patients with non‐colitis‐associated aneuploid colorectal carcinomas, in which the levels ranged from 1.1 to 2.0 with a median value of 1.5. Accordingly, the DNA index in the colitis patients with aneuploidy was more often within the tetraploid region. These results, obtained in patients with ulcerative colitis, indicate a possible precancerous progress from diploidy over tetraploidy to triploidy also in patients with long‐standing ulcerative colitis. In addition, the results speak in favour of a connection between DNA indices in the triploid region and more profound premalignant alterations

Human Colorectal Cancers with an Intact p16/Cyclin D1/pRb Pathway Have Up-Regulated p16 Expression and Decreased Proliferation in Small Invasive Tumor Clusters

A systematic spatial heterogeneity with high proliferative activity at the luminal border and low activity at the invasive margin is an unexpected behavior that has been observed in colorectal cancer (CRC). To clarify this phenomenon and possible underlying regulatory mechanisms, we have by immunohistochemistry elucidated the proliferative activity and the expression of G1/S regulatory proteins in small and large tumor cell clusters at the invasive margin in 97 CRCs. By identifying small tumor clusters at the tumor front, actually invading cancer cells could be characterized and analyzed separately. These cells could then be compared with the main tumor mass represented by the larger tumor clusters. The proliferation was significantly lower in small tumor clusters compared with larger clusters (P < 0.001) and the decrease in proliferation was correlated with a p16 up-regulation (rs = −0.41, P < 0.001). Interestingly, CRCs lacking p16 expression (18%) or tumors with other aberrations in the p16/cyclin D1/pRb pathway had a less pronounced decrease in proliferation between large and small clusters (P < 0.001), further strengthening the association between p16 and ceased proliferation at the invasive margin. This contrasts to tumors with low p27 or abnormal p53 levels showing sustained proliferation in small tumor clusters. Our findings imply that invading CRC cells generally have low proliferative activity, and this phenomenon seems to be mediated through p16 and the p16/cyclin D1/pRb pathway

<it>COL11A1</it> in FAP polyps and in sporadic colorectal tumors

Abstract Background We previously reported that the α-1 chain of type 11 collagen (COL11A1), not normally expressed in the colon, was up-regulated in stromal fibroblasts in most sporadic colorectal carcinomas. Patients with germline mutations in the APC gene show, besides colonic polyposis, symptoms of stromal fibroblast involvement, which could be related to COL11A1 expression. Most colorectal carcinomas are suggested to be a result of an activated Wnt- pathway, most often involving an inactivation of the APC gene or activation of β-catenin. Methods We used normal and polyp tissue samples from one FAP patient and a set of 37 sporadic colorectal carcinomas to find out if the up-regulation of COL11A1 was associated with an active APC/β-catenin pathway. Results In this study we found a statistically significant difference in COL11A1 expression between normal tissue and adenomas from one FAP patient, and all adenomas gave evidence for an active APC/β-catenin pathway. An active Wnt pathway has been suggested to involve stromal expression of WISP-1. We found a strong correlation between WISP-1 and COL11A1 expression in sporadic carcinomas. Conclusions Our results suggest that expression of COL11A1 in colorectal tumors could be associated with the APC/β-catenin pathway in FAP and sporadic colorectal cancer.</p