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In fact, it is one of the most investigated molecules in the metastatic process of several malignancies, among them that of colorectal cancer. One of the candidates of key importance has been CD44. Characterising the metastases associated processes is therefore of crucial importance for identifying ways of earlier and more sensitive diagnosis, more defined prognosis, and possibly in the selection of patients for targeted therapies.Ī variety of genes have been described and extensively investigated in the literature as key candidates in the tumorigenesis and progression of colorectal carcinoma, including APC, p53, K-ras, BRAF, DCC, MSH, EGFR, SFK, TGFR2, SMAD4, etc.Įach individual step of the metastatic cascade is the result of complex molecular interactions, regulated by several already identified and/or unidentified genes. In developed countries, colorectal cancer (CRC), or rather its progression to metastatic disease, accounts for 25% of tumour deaths. This fact and the huge potential number of different CD44 splice variants that can contain v3 and v6 domains can explain incoherence of clinical studies regarding functional asessment of CD44 variants, as well as diminish the chances of using CD44 variants for predictive purpose. However, this function may just affect a minority of tumour subclones. Particular CD44 variant isoforms seem to act as “metastasis genes” via tumour microenvironment-driven shifts in v3 and v6 expressions.
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Finally, on quantitative assessment of the variable exons v3 and v6, higher co-expression levels were found to be characteristic to metastatically potent tumour cells. Furthermore, we report a unique roster of all expressed CD44 variant isoforms characteristic to colorectal cancer. We managed to present a colorectal cancer-specific CD44 ASP, which remained unchanged from cell lines throughout primary tumour formation and metastatic progression. A complex preclinical experimental set-up was established to separately test the different steps of tumour progression and the role of tumour microenvironment, respectively, focusing on the role of ‘CD44’ in this process. This ASP was further investigated in terms of its qualitative and quantitative stability in our experimental iso- and xenograft mouse models for colorectal cancer progression.
#Splice serum serial number series
We compared the CD44 alternative splice pattern (ASP) of three genetically different human colorectal cancer cell lines (HT25, HT29, HCT116) using a series of PCR reactions and next- generation sequencing method, as well as identified a colorectal adenocarcinoma specific CD44 ASP. However, little consideration is given to the above in the literature of colorectal carcinomas as well as other tumour types, leading to confusion and contradictory results about its possible role in tumour progression.
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CD44 is considered as ‘a’ metastasis associated gene, despite the fact that it is an umbrella term for a group of molecules produced from a single gene by alternative splicing.