Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0345904 (liver cancer)
 15,188 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pathogenetic mechanisms of hepatocellular carcinoma (HCC) are still unclear and new tools for diagnostic and therapeutic purposes are ongoing. We have assessed whether squamous cell carcinoma antigen (SCCA), a serpin overexpressed in neoplastic cells of epithelial origin, is also expressed in liver cancer. Squamous cell carcinoma antigen was evaluated by immunohistochemistry in 65 HCCs of different aetiology and in 20 normal livers. Proliferative activity was assessed using MIB-1 antibody. In 18 surgical samples, tumour and nontumour liver tissue was available for SCCA cDNA amplification and sequencing. Squamous cell carcinoma antigen was detected in 55 out of 65 (85%) tumour specimens, but in none of the 20 controls. In the majority of the cases, the positive signal was found in the cytoplasm of more than 50% of the hepatocytes. Low or undetectable SCCA (score<or=1) was associated to lower MIB-1 labelling index, compared to cases with SCCA score >or=2 (mean+/-s.d.: 2%+/-2.4 vs 7.5%+/-10.3, P<0.05). Squamous cell carcinoma antigen mRNA could be directly sequenced in 14 out of 18 liver tumours but in none of the corresponding nontumour samples. From sequence alignment, a novel SCCA1 variant (G(351) to A) was identified in five cases, while SCCA1 was revealed in six cases and SCCA2 in three cases. In conclusion, SCCA variants are overexpressed in HCC, independently of tumour aetiology. A novel SCCA1 variant has been identified in one third of liver tumours.
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PMID:Overexpression of squamous cell carcinoma antigen variants in hepatocellular carcinoma. 1497 Aug 61

SERPINB3 (Squamous Cell Carcinoma Antigen, SCCA1) is a member of the ov-serpins, a serine protease inhibitors family expressed in many cell types including normal epithelium, leukocytes, tumors of epithelial origin and primary liver cancer. Several studies, carried out in vitro and in vivo, have documented an important role of SERPINB3 in the modulation of programmed cell death by different mechanisms, both in inflammatory processes and in cancer. SERPINB3 significantly attenuates apoptosis by contrasting cytochrome c release from the mitochondria and by antichemotactic effect for NK cells. Mechanisms involved in apoptosis induction and regulation play a key role in the balance between cell proliferation and death. Imbalance of this equilibrium may contribute to the development of autoimmune diseases, as defective apoptosis of immune cells leads to deregulated autoreactive cell proliferation. Since defective programmed cell death represents a critical feature of autoimmunity, the involvement of SERPINB3 in this pathological field deserves further studies.
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PMID:SERPINB3, apoptosis and autoimmunity. 1933 50

SERPINB3 (formerly known as squamous cell carcinoma antigen-1 or SCCA1) is a member of the family of serine-protease inhibitors. SERPINB3 protects cells from oxidative stress conditions, but in chronic liver damage this serpin may lead to hepatocellular carcinoma through different strategies, including inhibition of apoptosis, induction of epithelial to mesenchymal transition and decrease of desmosomal junctions, cell proliferation and invasiveness. SERPINB3 may also contribute to tumor cell resistance to anti-neoplastic drugs through its binding to the respiratory Complex I, protecting cells from the pro-oxidant action of chemotherapeutic agents. Mechanisms of tumor growth promotion induced by SERPINB3 include the inhibition of intratumor infiltration of natural killer cells, up-regulation of Myc oncogene and the recent identification of this serpin as a Ras-responsive factor. In the liver SERPINB3 and SERPINBB4 isoforms (known as squamous cell carcinoma antigen or SCCA) are undetectable in normal hepatocytes, but their expression progressively increases in chronic liver diseases, dysplastic nodules and hepatocellular carcinoma. High SERPINB3 levels have been recently detected in HCC tissue of patients with early tumor recurrence after surgical resection. In serum SERPINB3/4 isoforms (or SCCA) are detectable bound to IgMs (SCCA-IgM) in the majority of HCV infected patients with HCC and in patients with cirrhosis their levels and/or the progressive increase have been found correlated to the risk of HCC development. Preliminary findings in patients with HCC revealed that SCCA-IgM was predictive of HCC prognosis, since low levels of this biomarker were able to identify HCC patients with long overall and progression-free survival.
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PMID:Role of SERPINB3 in hepatocellular carcinoma. 2533 58

Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer and the third cause of cancer deaths. The leading predisposing condition is represented by an underlying viral hepatitis, mainly sustained by hepatitis B and C viruses. Since the cumulative risk of developing HCC can be as high as 30-fold in patients with infectious cirrhosis, a timely diagnosis is necessary for establishing an appropriate treatment in these patients. The armamentarium of diagnostic and prognostic biomarkers in patients with HCC currently entails alpha-fetoprotein (AFP) and a limited number of innovative biomarkers, among which squamous cell carcinoma antigen (SCCA) and its immune complexes are among the most widely investigated. The clinical data published so far and reviewed in this article seemingly suggest that neither total serum SSCA or its isoform 1 (i.e., SCCA1) may be ready for the prime time for management of patients with HCC. More interesting evidence has emerged from studies investigating the serum values of SCCA-IgM, since the diagnostic performance of this biomarker was found to be frequently superior to that of AFP and, even more importantly, the combination of SCCA-IgM and AFP was characterized by a much better sensitivity than either biomarker alone, with only a modest decrease of specificity. Larger studies are needed before these preliminary findings can be generalized, but the combined use of AFP and SCCA-IgM represents an appealing perspective in diagnosis and prognostication of HCC.
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PMID:Squamous cell carcinoma antigen in hepatocellular carcinoma: Ready for the prime time? 2584 50