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1、The Association of Schistosomiasis and Inflammatory Bowel Disease with Colorectal Cancer: Tools for Diagnosis and EpidemiologyPeter Chun, Ph.D In Egypt, schistosomiasis ( from S. haematobium and mansoni)has been strongly linked to bladder cancer. The evidence includes:Epidemiological evidenceExperim

2、entally induced schistosomiasisHistopathology Age and gender ratios M. H. Mostafa et al. Relationship between Schistosomiasis and Bladder Cancer. Clin Microbiol Rev 1999. 12(1)97-111The evidence linking S. manosini & haematobium infection to cancer of the large intestine is scant, but intestinal inf

3、estation with S. japonicum is considered a significant contributory factor to the development of cancer of the colon and rectum.A. Ishii et al. Parasitic infection and cancer: with special emphasis on Schistosoma japonicum infections (Trematoda). A review. Mutat Res. 1994 305(2)273-81Colorectal canc

4、er correlates with prevalence and intensity of shistosome infection.The age of onset of cancer is lower in areas of shcistosome endemicity and length of survival is shorter.Affected individuals usually have a long history of inflammatory large bowel symptoms.The cancers correspond in anatomic locati

5、on to the area most affected by the parasite.Z. Xu et at. Schsitosoma japonicum and colorectal cancer: an epidemiological study in the Peoples Republic of China. Int J Cancer. 1984. 34(3):315-8C. Ming-Chai et al. Evolution of colorectal cancer in schistosomiasis: transitional mucosal changes adjacen

6、t to large intestinal carconoma in colectomy specimens Cancer 1980. 46(7):1661-75Chen et al. Colorectal cancer and schistosomiasis. Lancet 1981 971-3ES. Zhao et al. Carconoma of the large instestine with schistosomiasisanalysis of 279 cases. Zhonghua Zhong Liu Za Zhi. 1981 3(1):67-9ES Zhao. Cancer o

7、f the colon and schistosomiasis. J R Soc Med. 1981 74(9):645K. Shindo. Significance of schistosomiasis japonica in the development of cancer of the large intestine. Dis Colon Rectum 1976; (19) 460-9K. Inoguchi et al. The correlation between primary colorectal carcinoma and schistosomiasis japonica.

8、Igakku Kenkyu 1978; (48)93-9K. Matsuda et al. Possible Associations of Rectal Carcinoma with Schistosoma japonicum Infection and Membranous Nephropathy: a Case Report with a Review. Japanese J Clin Oncol (29)576-581 Pathologically, patients with colonic schistosomiasis manifest epithelial dysplasia,

9、 and resemble the changes found in long-standing chronic ulcerative colitis. Chen et al. considered these dysplastic changes as premalignant lesions. Chen et al. Colorectal cancer and schistosomiasis. Lancet 1981 971-3The evidence associating colorectal cancer and ulcerative colitis and Crohns disea

10、se is strong. Tumors often occur at the site of chronic inflammation. The absolute risk of developing colorectal hanker is high when extensive disease begins at a young age. 40% of patients diagnosed with pancolitis from ulcerative colitis before age 15 years developed colon cancer during 20 years o

11、f follow up in a population-based linkage study in Sweden. DK Podolsky. Inflammatory bowel disease. N Engl J Med. 2002. 347:417-429S. japonicum lays a very large number of egg, and represents a constant source of irritation.Inflammation involves a series of host reponses that is designed to promote

12、healing and tissue regeneration. These include recruiting specific types of cells, release of mediators and interactions of chemokines with various targets that affect cytological changes. Leukocytes generate reactive oxygen and nitrogen radicals which can damage proteins, membranes and DNA (includi

13、ng the genes controlling cell growth & proliferation). Inflammatory cells also release factors that inhibit apoptosis, induce angiogenesis, and impair certain immune responses. Collectively, these factors can accelerate mutagenesis, promote the survival and clonal proliferation of mutated cells, som

14、e of which may become invasive and metastatic. M. Thun et al. Inflammation and cancer: an epidemiological perspecitive. In 2004 Cancer and Inflammation. Wiley, Chichester (Novartis Foundation Symposium 256). P6-28. We describe here two membrane based colloidal gold tests which can aid in the detecti

15、on of inflammatory bowel disease and schistosomiasis. Both are easy to perform and can be done at the clinic level at the same time that other screening tests for colorectal cancer are done.We propose the use of these new tests to secure large scale epidemiological evidence linking these two disease

16、s to colorectal cancer in ChinaTests for Fecal Occult BloodChemical TestsPrinciple: Based on peroxidase activity of heme.Advantages: Sensitive, Inexpensive. Will detect digested blood. Quantitation possible.Disadvantages: Not specific. Dietary restriction required.Immunological TestsPrinciple: Based

17、 on detection of human hemoglobin.Advantages: Very specific. No dietary restrictions.Disadvantages: Expensive. More complex to perfom. Examples of Chemical TestsChromogens: O-tolidine/Benzidine, Guaic, Pyramidon.Example of Immunological TestAn algorithm which uses a two stage testing protocol is muc

18、h more cost effective given the price difference between the chemical and immunological tests for fecal occult blood.Immunochemical vs. Guaiac Fecal Occult Blood Tests. 2004. Technology Evaluation Center.Assessment Program vol 19, No. 5. Blue Cross & Blue Shield Association.( A 27 page review.) Othe

19、r non-invasive commercial tests available today:PreGen-Plus from Exact Sciences Corp. (exactsciences)Detection of altered DNA from exfoliated cells in stool specimen. A comparison was made among four neutrophil-derived proteins in stool as an indicator of disease activity in ulcerative colitis. J. L

20、anghorst et al. Digestive Disease Week. May 2004. New Orleans, LA.SensitivitySpecificityCorrelation Lactoferrin 86.4% 69.8% 0.75(above 7.25 ug/g)PNM-Elastase 81.8% 48.8% 0.60(above 0.062ug/g)Calprotectin 72.7% 60.5% 0.65(above 6 ug/g)Lysozyme 54.5% 48.8% 0.55(above 0.6 ug/g)IBD-Scan: A commercial qu

21、antitative ELISA for measuring fecal lactoferrin.techlabThere is a need for a rapid test for lactoferrin.An immunochromatographic test using polyclonal antibodies: a sandwich immunoassay with colloidal gold as visualization reagent. Instruments which allow for quantitationInstruments which allow for quantitationFlow through membrane test for detecting S. japonicum antibodiesTTest spotAnti

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