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)

Alpha-fetoprotein (AFP) represents the most important biomarker for hepatocellular carcinoma (HCC). The aim of this study was to identify the optimal staging system to predict the survival of AFP-negative and AFP-positive patients. This study analyzed the data of 431 AFP-negative HCC patients who had previously undergone surgery and 471 AFP-positive HCC candidates. Kaplan-Meier (K-M) survival estimates were plotted, and the P values were assessed using log-rank tests. The Akaike information criterion (AIC) was calculated using the results of a Cox's regression to compare the overall assessment of the seven different staging systems. The AFP-positive group displayed characteristics of poor tumor biological behavior (tumor multiplicity [P = 0.032], low grade differentiation [P = 0.000] and carcinoma cell embolus [P = 0.031]), poor liver function (Child-Pugh B classification [P = 0.003], abnormal prothrombin time activity [P = 0.037] and moderate/severe cirrhosis [P = 0.000]) and increased operative difficulties (transfusion; P = 0.001). TNM7th staging showed the lowest AIC value (1,279.528) for the AFP-negative group, while the Barcelona Clinic Liver Cancer (BCLC) staging system revealed the lowest AIC value (1,991.233) for the AFP-positive group. In conclusion, among the seven favorable staging systems, BCLC staging was superior for the AFP-positive group, while the TNM7th was a more appropriate staging model for the AFP-negative group.
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PMID:Evaluation of seven different staging systems for alpha-fetoprotein expression in hepatocellular carcinoma after hepatectomy. 2332 23

Growth and antigrowth hormones were occasionally investigated in hepatocarcinoma. Somatostatin regulates cell proliferation and inhibits the secretion of many growth factors engaged to tumors through a group of receptors, including somatostatin receptor type 2 (SSTR2). Caspase-3 is a transcription factor which is elevated in liver cancers. The most commonly approved marker for liver cancer is alpha fetoprotein (AFP), although it has no more than 65% sensitivity and specificity. Hepatocarcinoma is also mediated by oxidative stress. Four groups of mice were used in this work: a control group and another three groups (Gp 2, 3, and 4) used for induction of HCC with a single subnecrotic dose of diethylnitrosamine (DENA). Gp 2 was sacrificed on the last day after 8 weeks, Gp 3 after 16 weeks, and Gp 4 after 24 weeks. Both liver tissue SSR2 protein and mRNA, liver AFP, and caspase-3 mRNA expression, concomitant to tissue malondialdehyde (MDA), were significantly elevated with depressed reduced glutathione (GSH). The change was much more prominent and stage dependent for SSR2. These effects were supported by graded histological abnormalities. The study encourages the use of liver tissue SSR2 protein and mRNA as a reliable tumor marker for liver cancer rather than AFP which is always misleading during silent stages of hepatocarcinogenesis.
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PMID:Hepatic somatostatin receptor 2 expression during premalignant stages of hepatocellular carcinoma. 2416 59

Alpha-fetoprotein not only serves as a diagnostic marker for liver cancer, but also posses a variety of biological functions. However, the role of Alpha-fetoprotein on tumor angiogenesis and cell invasion remains incompletely understood. In this study, we aimed to evaluate if Alpha-fetoprotein can regulate the major angiogenic factors and matrix metalloproteinases in human liver cancer cells. Alpha-fetoprotein silencing was achieved by Stealth RNAi. Expression of Alpha-fetoprotein was examined by a full-automatic electrochemistry luminescence immunity analyzer. Expression of VEGF, VEGFR-2, MMP-9, and MMP-2 was examined by Western blot and immunocytochemistry. Apoptosis was detected by TUNEL assay. Angiogenesis was detected by in vitro angiogenesis assay kit. Silencing of Alpha-fetoprotein led to an increased apoptosis, which was associated with a decreased expression of vascular endothelial growth factor, vascular endothelial growth factor receptor 2, matrix metalloproteinases-2/9. These results suggest that Alpha-fetoprotein may play a regulatory role on angiogenesis and cell invasion during liver cancer development.
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PMID:Silencing alpha-fetoprotein inhibits VEGF and MMP-2/9 production in human hepatocellular carcinoma cell. 2458 7

Hepatocellular carcinoma diagnosis and treatment has witnessed many major changes and challenges in the past two decades. Increasing incidence of HCC has introduced new monitoring systems and increased the efficacy of screening tests, as well as prognosis of the disease, including the staging system, serological testing and diagnostic imaging. Moreover, surgical resection, liver transplantation and herbal therapy have improved treatment. The most encouraging specific serological marker for HCC is alpha fetoprotein (AFP), which, along with ultrasonography, has improved earlier detection of HCC. Most recently, circulating tumor cell measurement has emerged as a promising tool for the prognosis of HCC. Herbal drugs and herbal composite formula drugs are promising towards the prevention of invasion and proliferation of tumor cells. Chemotherapeutic agents, such as sorafenib, bevacizumab and erlotinib, which target growth factor receptors in signaling pathways, are also used as HCC treatments. Furthermore, radiotherapy is employed in the treatment of unresectable tumors. The present report provides an analysis of the above parameters in the management of HCC.
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PMID:New possibilities in hepatocellular carcinoma treatment. 2469 83

Identification of novel biomarkers for tumor-initiating cells (TICs) is of critical importance for developing diagnostic and therapeutic strategies against cancers. Here we identified the role of KIAA1114, a full-length translational product of the trophinin gene, as a distinctive marker for TICs in human liver cancer by developing a DNA vaccine-induced monoclonal antibody targeting the putative extracellular domain of KIAA1114. Compared with other established markers of liver TICs, KIAA1114 was unique in that its expression was detected in both alpha fetoprotein (AFP)-positive and AFP-negative hepatocellular carcinoma (HCC) cell lines with the expression levels of KIAA1114 being positively correlated to their tumorigenic potentials. Notably, KIAA1114 expression was strongly detected in primary hepatic tumor, but neither in the adjacent non-tumorous tissue from the same patient nor normal liver tissue. KIAA1114high cells isolated from HCC cell lines displayed TIC-like features with superior functional and phenotypic traits compared to their KIAA1114low counterparts, including tumorigenic abilities in xenotransplantation model, in vitro colony- and spheroid-forming capabilities, expression of stemness-associated genes, and migratory capacity. Our findings not only address the value of a novel antigen, KIAA1114, as a potential diagnostic factor of human liver cancer, but also as an independent biomarker for identifying TIC populations that could be broadly applied to the heterogeneous HCC subtypes.
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PMID:KIAA1114, a full-length protein encoded by the trophinin gene, is a novel surface marker for isolating tumor-initiating cells of multiple hepatocellular carcinoma subtypes. 2471 74

A young man presented with a large liver mass and positive hepatitis B virus markers. This 18-year-old male has developed ascites, jaundice, high serum alpha fetoprotein (AFP) level, liver mass and portal hypertension, without fever or calcification in the mass. All favored the diagnosis of rapidly, progressive hepatocellular carcinoma, however proven hepatoblastoma in liver biopsy. Hepatoblastoma usually manifests prior to the third year of life, but can rarely be seen in older children or adults. Although HCC rarely can be presented in young patients with HBV infection, but in patients without cirrhosis hepatoblastoma should be considered as the first possible diagnosis.
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PMID:An 18-year-old man with hepatitis B virus infection and hepatoblastoma. 2482 53

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, and is advanced by severe viral hepatitis B or C (HBV or HCV) as well as alcoholic liver disease. Many patients with early disease are asymptomatic therefore HCC is frequently diagnosed late requiring costly surgical resection or transplantation. The available non-invasive detections systems are based on the clinical utility of alpha fetoprotein (AFP) measurement, together with ultrasound and other more sensitive imaging techniques. The hallmark of liver disease and its propensity to develop into fully blown HCC is depended on several factors including the host genetic make-up and immune responses. While common symptoms involve diarrhea, bone pain, dyspnea, intraperitoneal bleeding, obstructive jaundice, and paraneoplastic syndrome, the evolution of cell and immune markers is important to understand viral induced liver cancers in humans. The circulating miRNA, cell and immune based HCC biomarkers are imperative candidates to successfully develop strategies to restrain liver injury. The current molecular genetics and proteomic analysis have lead to the identification of number of key biomarkers for HCC for earlier diagnosis and more effective treatment of HCC patients. In this review article, we provide latest updates on the biomarkers of HBV or HCV-associated HCC and their co-evolutionary relationship with liver cancer.
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PMID:Biomarkers for virus-induced hepatocellular carcinoma (HCC). 2495 36

The mesenchymal-epithelial transition factor (c-Met) is a receptor tyrosine kinase with hepatocyte growth factor (HGF) as its only high-affinity ligand. Aberrant activation of c-Met is associated with many human malignancies, including hepatocellular carcinoma (HCC). We investigated the in vivo antitumor and antimetastatic efficacy of the c-Met inhibitor MSC2156119J (EMD 1214063) in patient-derived tumor explants. BALB/c nude mice were inoculated with MHCC97H cells or with tumor fragments of 10 patient-derived primary liver cancer explants selected according to c-Met/HGF expression levels. MSC2156119J (10, 30, and 100 mg/kg) and sorafenib (50 mg/kg) were administered orally as single-agent treatment or in combination, with vehicle as control. Tumor response, metastases formation, and alpha fetoprotein (AFP) levels were measured. MSC2156119J inhibited tumor growth and induced complete regression in mice bearing subcutaneous and orthotopic MHCC97H tumors. AFP levels were undetectable after 5 weeks of MSC2156119J treatment, and the number of metastatic lung foci was reduced. Primary liver explant models with strong c-Met/HGF activation showed increased responsiveness to MSC2156119J, with MSC2156119J showing similar or superior activity to sorafenib. Tumors characterized by low c-Met expression were less sensitive to MSC2156119J. MSC2156119J was better tolerated than sorafenib, and combination therapy did not improve efficacy. These findings indicate that selective c-Met/HGF inhibition with MSC2156119J is associated with marked regression of c-Met high-expressing tumors, supporting its clinical development as an antitumor treatment for HCC patients with active c-Met signaling.
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PMID:The c-Met Inhibitor MSC2156119J Effectively Inhibits Tumor Growth in Liver Cancer Models. 2525 30

The role of transcatheter arterial chemoembolization (TACE) prior to curative therapy is still unclear. The aim of our study was to elucidate the survival of single hepatocellular carcinoma (HCC) and also to clarify whether TACE plus sequential curative therapy provides benefits in single HCC. A total of 470 patients with a diagnosis of single HCC between 2005 and 2010 were studied. The factors associated with clinical outcomes were analyzed. The outcomes between patients who underwent neoadjuvant TACE and those who did not were also compared. The 1-, 3-, and 5-year overall survival (OS) rates of all patients were 92.6%, 73.3%, and 59.6%, respectively. Child-Pugh class A [HR: 2.04, 95% confidence interval (CI): 1.277-3.254, p = 0.003], very early stage Barcelona Clinic Liver Cancer (BCLC) (HR: 2.03, 95% CI: 1.021-4.025, p = 0.043), tumor size < 5 cm (HR: 1.75, 95% CI: 1.115-2.751, p = 0.015), alpha fetoprotein (AFP) level < 200 ng/mL (HR: 2.07, 95% CI: 1.346-3.182, p = 0.001), and curative-based therapy (HR: 2.16, 95% CI: 1.442-3.224, p < 0.001) were factors associated with better OS. The 1-, 3-, and 5-year disease-free survival (DFS) rates of all the patients were 75.4%, 53.7%, and 36.3%, respectively. Only Child-Pugh class A (HR: 1.57, 95% CI: 1.068-2.294, p = 0.022) and curative-based therapy (HR: 1.51, 95% CI: 1.128-2.028, p = 0.006) were significantly associated with better DFS. Neoadjuvant TACE did not provide benefit compared with curative therapy alone in subgroup analysis. In conclusion, neoadjuvant TACE is not recommended in single HCC patients who may indicate for curative therapy.
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PMID:Neoadjuvant transcatheter arterial chemoembolization does not provide survival benefit compared to curative therapy alone in single hepatocellular carcinoma. 2564 85

Hepatocellular carcinoma is the 5(th) most common cancer in men and the 2(nd) common cause of death from cancer worldwide. The tumour commonly metastasizes to the lungs, regional lymph nodes and bone. Spinal cord compression secondary to metastatic disease as a first presentation is uncommon. We describe a patient who presented with paraplegia as a first presentation of hepatocellular carcinoma. 46 year old Namibian man presented with progressive leg weakness that was associated with a dull back ache and inability to pass urine and stool. He had no history of trauma nor did he have chronic cough, night sweats or fevers. He has been treated several times for alcohol dependence. On examination he was wasted, power 0/5 in both lower limbs and a sensory level at T12. He also had a non-tender hepatomegaly with Alpha-fetoprotein of 2000. The Chest X-ray and Chest CT showed nodular opacities indicating metastatic disease and the X-ray and CT of the thoracic spine showed osteolytic lesion with destruction of the pedicle of L1. Liver and spinal biopsy confirmed the hepatocellular carcinoma. The extra hepatic manifestations of HCC are diverse and Spinal cord metastasis is of pertinent clinical importance and should thus be greatly considered.
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PMID:Spinal cord compression: an unusual presentation of hepatocellular carcinoma. 2593 76


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