Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C1864663 (HCC)
 2,985 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 58-year-old man was followed up for HBV-associated chronic hepatitis. A low echoic hepatic nodule 1.6cm in diameter developed in segment 8 of the liver. The tumor was hypervascular and showed enhancement on CV during hepatic arteriography (CTHA) and a defect on CT during arterial portography (CTAP). Strong enhancement, which lasted for 30 seconds, was observed at the margin of the tumor on single-level dynamic CTHA. The resected tumor was whitish, had no capsule, and consisted mainly of intermediate immature cells together with HCC-like and CCC-like tumor cells. These findings led to the diagnosis of primary liver carcinoma of intermediate (hepatocyte-cholangiocyte) phenotype. Cytokeratin (CK) 7, CK8, CK19, EMA and vimentin were positive and HP-1 and c-kit tests were negative on immunohistochemical staining. Staining with CD34+alphaSMA showed more muscular arterial vessels and sinusoid-like vessels in the peripheral zone of the tumor than in the central zone. Six months after the resection of the tumor, swollen abdominal lymph nodes were observed on US and CT, which aspiration needle biopsy showed to be metastasis of a hepatic tumor.
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PMID:[A case of primary liver carcinoma of intermediate (hepatocyte-cholangiocyte) phenotype: comparison of hemodynamics and histopathology]. 2020 49

Combined hepatocellular carcinoma and cholangiocarcinoma (combined HCC-CC) is a rare subtype of primary liver cancer. We investigated the histopathologic features of transitional or intermediate areas in 21 combined HCC-CCs and immunophenotypes using different hepatic progenitor cell markers (CK7, CK19, c-kit, NCAM, and EpCAM). Major histologic findings of transitional or intermediate areas of 21 combined HCC-CCs included strands/trabeculae of small, uniform, oval-shaped cells with scant cytoplasm and hyperchromatic nuclei embedded within an abundant stroma, small cells with an antler-like anastomosing pattern, and solid nests of intermediate hepatocyte-like cells surrounded by small cells in periphery, in order of frequency. The intermediate area of one tumor was composed predominantly of spindle cells arranged in short fascicles. Immunophenotype of tumor cells with intermediate morphology suggested a progenitor cell origin for this tumor. Clinical findings of combined HCC-CC showed a closer resemblance with those of HCC than those of CC. In univariate analysis, tumor size, TNM stage, and serum alpha-fetoprotein levels showed a significant association with poor patient survival. Serum alpha-fetoprotein level was an independent prognostic indicator in multivariate analysis. In conclusion, an awareness of the clinicopathologic features, specifically the various morphologic features of intermediate areas in this tumor, is essential for prevention of potential misdiagnosis as another tumor.
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PMID:Clinicopathologic study on combined hepatocellular carcinoma and cholangiocarcinoma: with emphasis on the intermediate cell morphology. 2186 May 52

Sorafenib, a receptor tyrosine kinase-inhibitor with anti-proliferative and anti-angiogenic activity, is currently the only approved systemic treatment for patients with hepatocellular carcinoma. It inhibits downstream signaling of VEGFR-2, PDGFR, c-Kit receptors and BRAF. Over the last four years comprehensive experience with sorafenib in this indication has been accumulated. In this review we discuss the current data on the use of sorafenib in patients with advanced HCC including special patient populations such as patients with impaired liver function, patients after transplantation, and others. The most frequent side-effects and practical tips on how to manage them are discussed in detail. In addition, we summarize the current experimental data on the use of sorafenib in combination treatment, e. g., together with transarterial chemoembolisation or other targeted agents.
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PMID:Treatment of hepatocellular carcinoma with sorafenib - focus on special populations and adverse event management. 2296 33

Objective. The intrahepatic stem cells, also known as hepatic progenitor cells (HPCs), are able to differentiate into hepatocytes and bile duct epithelia. By exposure of different injuries and different hepatocarcinogenic regimens, the mature hepatocytes can no longer effectively regenerate; stem cells are involved in the pathogenesis of hepatocellular carcinoma. Methods. Immunohistochemistry was performed on 107 paraffin-embedded hepatocellular carcinoma specimens with the marker of hepatocyte and hepatocellular carcinoma (HepPar1), biliary differentiation (CK7,CK19), haemopoietic stem cell (HSC) (c-kit/CD117, CD34, and Thy-1/CD90), HPC specific markers (OV-6), and Ki-67, p53 protein. Results. HPCs can be identified in the tumor nodules, around the edge of tumor nodules, and in the portal tracts of the paracirrhosis nodules being positive in HepPar1, CK7, CK19, and OV-6, but they failed to immunostain with CD117, CD34, and CD90. The HPCs positive in Ki-67 are observed in the tumor and paracirrhosis tissues. In 107 specimens, 40.2% (43/107) HCC tissues expressed p53 protein, lower than that of the HPCs around the tumor nodules (46.7%, 50/107) and much higher than that of the HPCs around the paracirrhosis nodules (8.41%, 9/107). Conclusion. Human hepatocellular carcinogenesis may be based on transformation of HPCs, not HSCs, through the formation of the transitional cells (hepatocyte-like cells and bile ductal cells).
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PMID:Probing the hepatic progenitor cell in human hepatocellular carcinoma. 2353 83

The immune modulatory effect of tivozanib, a tyrosine kinase inhibitor, and the underlying immune mechanisms impacting survival of HCC patients have not been investigated. Pre-clinical studies have shown that tivozanib reduces Tregs and MDSCs accumulation through inhibition of c-Kit/SCF axis. We rationalized that c-Kit/SCF axis antagonism by tivozanib may reverse tumor-induced immune suppression in HCC patients. The frequency of circulating Tregs, MDSCs, CTLA-4+Tregs, PD-1+T cells, c-Kit+pERK-2+Tregs, and c-Kit+pERK-2+MDSCs were quantified in HCC patients at baseline and two time points during tivozanib treatment. We report for the first time that reduction in Tregs after tivozanib treatment and increased levels of baseline CD4+PD-1+T cells correlated with significant improvement in overall survival (OS) of the patients and these signatures may be potential biomarkers of prognostic significance. This immune modulation resulted from tivozanib-mediated blockade of c-Kit/SCF signaling, impacting ERK2 phosphorylation on Tregs and MDSCs. Low pre-treatment CD4+T cells: Treg ratio and reduction in the frequencies of Foxp3+c-Kit+pERK+Tregs after tivozanib treatment correlated significantly with progression free survival. In a comparative analysis of tivozanib vs sorafenib treatment in HCC patients, we demonstrate that decrease in the baseline numbers or frequencies of Foxp3+Tregs, MDSCs and exhausted T cells was significantly greater following tivozanib treatment. Additionally, greater increase in CD4+T cell: Treg ratio after tivozanib treatment was associated with significant improvement in OS compared to sorafenib treatment, highlighting the greater efficacy of tivozanib. These insights may help identify patients who likely would benefit from c-Kit/SCF antagonism and inform efforts to improve the efficacy of tivozanib in combination with immunotherapy.
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PMID:Tivozanib mediated inhibition of c-Kit/SCF signaling on Tregs and MDSCs and reversal of tumor induced immune suppression correlates with survival of HCC patients. 3310 75