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PLEX SKIN Group

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Foetoprotein [NEW]



Alpha-foetoprotein (AFP), one of the first protein tumour markers discovered, is widely used today in clinical practice. Its application for the screening and diagnosis of hepatocellular carcinoma (HCC), the most frequent form of primary liver tumour, is a matter of extensive debate. In addition to the studies focused on the role of the AFP in the diagnosis of HCC, in recent years AFP has been used to guide the therapeutic choice in HCC and monitor the treatment. Here, we summarize the latest studies that show the interest of AFP quantification in determining the suitability of liver transplantation or to follow-up on patients receiving the targeted treatment sorafenib. We also highlight the recent studies showing the active role of AFP in tumour progression, and the new modes of regulation of this tumour marker. Among these is the regulation of AFP through tumour proteostasis and the Unfolded Protein Response (UPR). We discuss the implications of this new knowledge in the therapeutic context, in terms of interpreting serum levels of AFP, and the new perspectives offered by AFP for the study of tumour proteostasis.




foetoprotein



Background: Hepatocellular carcinoma (HCC) occurs mostly in people with chronic liver disease and ranks sixth in terms of global instances of cancer, and fourth in terms of cancer deaths for men. Despite that abdominal ultrasound (US) is used as an initial test to exclude the presence of focal liver lesions and serum alpha-foetoprotein (AFP) measurement may raise suspicion of HCC occurrence, further testing to confirm diagnosis as well as staging of HCC is required. Current guidelines recommend surveillance programme using US, with or without AFP, to detect HCC in high-risk populations despite the lack of clear benefits on overall survival. Assessing the diagnostic accuracy of US and AFP may clarify whether the absence of benefit in surveillance programmes could be related to under-diagnosis. Therefore, assessment of the accuracy of these two tests for diagnosing HCC in people with chronic liver disease, not included in surveillance programmes, is needed.


Hepatocellular carcinoma (HCC), i.e. cancer originating in the liver, is sixth in terms of global occurrences of cancer and fourth in terms of cancer deaths in men. This cancer occurs mostly in people with chronic liver disease regardless of the cause. Ultrasound (US), which uses ultrasound waves to show abnormalities in the liver, can detect the presence of liver lesions suspected of being HCC. Alpha-foetoprotein (AFP), a glycoprotein, produced by the liver and measurable in the blood, is considered a tumour-marker because high levels can be associated with the presence of HCC. These two tests (US and AFP) are used, alone or in combination, to exclude the presence of HCC in people at high risk of developing HCC. People at high risk are those who have chronic liver disease. Current guidelines recommend surveillance programmes, repeating abdominal US with or without AFP testing every six months to detect early HCC, amenable to surgical resection or other treatment.


Hepatocellular carcinoma (HCC) occurs mostly in people with chronic liver disease and ranks sixth in terms of global instances of cancer, and fourth in terms of cancer deaths for men. Despite that abdominal ultrasound (US) is used as an initial test to exclude the presence of focal liver lesions and serum alpha-foetoprotein (AFP) measurement may raise suspicion of HCC occurrence, further testing to confirm diagnosis as well as staging of HCC is required. Current guidelines recommend surveillance programme using US, with or without AFP, to detect HCC in high-risk populations despite the lack of clear benefits on overall survival. Assessing the diagnostic accuracy of US and AFP may clarify whether the absence of benefit in surveillance programmes could be related to under-diagnosis. Therefore, assessment of the accuracy of these two tests for diagnosing HCC in people with chronic liver disease, not included in surveillance programmes, is needed.


Monospecific anti-[rat alpha-foetoprotein(alpha-FP)] immunoglobulin G was coupled to CNBr-activated Sepharose-4B (4.5 mg/ml packed volume of gel) to yield an adsorbent. The immunoaffinity column was used to isolate alpha-FP from neonatal-rat skin. Purified skin alpha-FP was found to be immunologically and electrophoretically similar to serum alpha-FP. It yielded a single band with mol.wt. 68000 on sodium dodecyl sulphate/polyacrylamide-gel electrophoresis. However, on polyacrylamide-gel electrophoresis under non-denaturing conditions, the alpha-FP displayed slow- and fast-moving variants similar to those observed in serum alpha-FP. A Scatchard plot of oestradiol binding to the alpha-FP yielded an association constant of 2.5 10(9)M-1 by dextran-coated-charcoal and 0.75 10(8)M-1 by Sephadex-gel-filtration procedures respectively. Skin explants from newborn rats were found to incorporate [14C]leucine into immunoprecipitable intracellular alpha-FP. Cycloheximide inhibited the synthesis of alpha-FP in skin explant culture. Our results indicate that newborn-rat skin contains alpha-FP that is similar to serum alpha-FP and which may arise in neonatal-rat skin as a result of synthesis in situ. 041b061a72


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