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Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hepatocellular carcinoma (HCC) is the third cause of cancer-related death worldwide. Curative options for HCC are limited and exclusively available for patients carrying an early stage HCC. In advanced stages, traditional chemotherapy proved to be only marginally effective or even toxic. Thus, the identification of new treatment options is needed. New targets for non-conventional treatment will necessarily take advantage of progresses on the molecular pathogenesis of HCC. MicroRNAs (miRNAs) are a group of tiny RNAs with a fundamental role in the regulation of gene expression. Aberrant expression of several miRNAs was found to be involved in human hepatocarcinogenesis. miRNA expression signatures were correlated with bio-pathological and clinical features of HCC. In some cases, aberrantly expressed miRNAs could be linked to cancer-associated pathways, indicating a direct role in liver tumourigenesis. For example, up-regulation of mir-221 and mir-21 could promote cell cycle progression, reduce cell death and favour angiogenesis and invasion. These findings suggest that miRNAs could become novel molecular targets for HCC treatment. The demonstration of in vivo efficacy and safety of anti-miRNA compounds has opened the way to their use in clinical trials.
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PMID:MicroRNA involvement in hepatocellular carcinoma. 1912 Jul 3

Nanoparticles of poly(DL-lactide-co-glycolide) (PLGA) in the size range 90-150 nm were produced using the physicochemical method with solvent/non-solvent systems. The encapsulation of the ascorbic acid in the polymer matrix was performed by homogenization of the water and organic phases. In vitro degradation and release tests of PLGA nanoparticles with and without encapsulated ascorbic acid were studied for more than 60 days in PBS and it has been determined that PLGA completely degrades within this period, fully releasing all encapsulated ascorbic acid. The cytotoxicity of PLGA and PLGA/ascorbic acid 85/15% nanoparticles was examined with human hepatoma cell lines (HepG2 ECACC), in vitro. The obtained results indicate that neither PLGA nanospheres nor PLGA/ascorbic acid 85/15% nanoparticles significantly affected the viability of the HepG2 cells. The investigation of the distribution and pharmacokinetics of PLGA is crucial for the effective prediction of host responses to PLGA in particular applications. Thus we present a method of labeling PLGA nanospheres and PLGA/ascorbic acid 85/15 wt% nanoparticles by (99m)Tc which binds outside, leaving the cage intact. This enables a quick and convenient investigation of the pharmacological behavior and metabolism of PLGA. The biodistribution of (99m)Tc-labeled PLGA particles with and without encapsulated ascorbic acid after different periods of time of their installation into rats was examined. PLGA nanospheres with encapsulated ascorbic acid exhibit prolonged blood circulation accompanied by time-dependent reduction in the lungs, liver and spleen, and addition in the kidney, stomach and intestine. The samples were characterized by x-ray diffraction, scanning electron microscopy, stereological analysis, transmission electron microscopy, ultraviolet spectroscopy and instant thin layer chromatography.
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PMID:An innovative, quick and convenient labeling method for the investigation of pharmacological behavior and the metabolism of poly(DL-lactide-co-glycolide) nanospheres. 1963

Osteopontin (OPN, SPP1) is a secretory extracellular matrix protein that has been implicated in cancer-associated mechanisms such as metastasis, invasion and angiogenesis. Three OPN isoforms (OPN-a, -b and -c) derived from alternative splicing are known to exist, but their functional specificity remains unclear. Here, we found that the expression profile of OPN isoforms in hepatocellular carcinoma (HCC) cell lines and patient tissues were correlated with specific cellular phenotypes and tumorigenicity of HCC. Thus, SK-Hep1 cells with a robust migratory capacity dominantly expressed both OPN-a and -b, but non-migratory cell lines such as Hep3B and PLC/PRF/5 mainly expressed OPN-c. Moreover, tumor tissues predominantly expressed OPN-a and -b, whereas normal liver tissues mainly expressed OPN-c. Transwell infiltration and wound-induced migration assays revealed that both OPN-a and -b induced Hep3B cell migration, while OPN-c had no significant effects. By contrast, OPN-c suppressed the migratory activity of SK-Hep1 cells although no significant changes were induced by OPN-a. Consistently, OPN isoforms differentially activated migration-associated signaling pathways such that OPN-a and -b increased the expression of urokinase type plasminogen activator and the phosphorylation of p42/p44 MAP kinase, but these pathways were not activated by OPN-c. Thus, the findings of the present study suggest that OPN splice variants differentially couple to signaling pathways to modulate the migratory property of HCC cells and that this is one of the mechanisms underlying the pathological heterogeneity of HCC progression.
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PMID:Osteopontin splice variants differentially modulate the migratory activity of hepatocellular carcinoma cell lines. 1988 63

The aim of this study was to determine the clinical characteristics of Behcet's disease (BD) complicated with malignancy in Korea. Of 1,769 patients with BD in our hospital, 32 patients (1.8%, 21 in solid cancer, 11 in hematologic malignancy) developed cancer. In 10 of the 32 subjects (31.3%), malignancy was diagnosed before or concomitantly with BD. Twelve cases (37.5%) occurred within the first 2 years of disease and 9 cases (28.1%) occurred 5 years after the diagnosis of BD. Myelodysplastic syndrome (MDS) was the most common disease (n = 7) followed by thyroid cancer (n = 4), breast cancer, cervix cancer, stomach cancer, rectal cancer, hepatoma, aplastic anemia (n = 3, each), renal cell cancer, endometrial cancer, lymphoma (n = 1, each). There were no significant differences in the clinical characteristic between patients with or without malignancy. Intestinal involvement were more frequent in patients with malignancy than those without, but was not statistically significant (p = 0.083). Our results demonstrate that MDS and thyroid cancer are the most common hematologic disease and solid cancer associated with BD, respectively. Further studies will be required to ascertain the pathogenic link between BD and malignancy and the prevalence of malignancy in BD.
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PMID:Behcet's disease associated with malignancy in Korea: a single center experience. 2001 87

The tumor suppressor protein p53 is a key regulator of cell cycle arrest and apoptosis. Snail protein regulates cancer-associated malignancies. However, the relationship between p53 and Snail proteins in hepatocellular carcinoma (HCC) has not been completely understood. To determine whether Snail and p53 contribute to hepatocarcinogenesis, we analyzed the expression of Snail proteins in p53-overexpressing HCC cells. We found that p53 wild-type (WT) induced the degradation of Snail protein via murine double minute 2-mediated ubiquitination, whereas p53 mutant did not induce Snail degradation. As we expected, only p53WT induced endogenous Snail protein degradation and inhibited tumor cell invasion. These findings contribute to a better understanding of the role of p53 mutation and Snail overexpression as a late event in hepatocarcinogenesis.
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PMID:p53 inhibits tumor cell invasion via the degradation of snail protein in hepatocellular carcinoma. 2038 33

Bone metastases account for 10% to 30% of secondary tumors in all cancer types. In patients with primary hepatocellular carcinoma (HCC), bone metastases are usually treated by nonoperative procedures including pain medication, radiotherapy, hormone therapy, chemotherapy, and bisphosphonates. Surgical treatments include vertebrectomy, reconstruction with a cage or polymethylmethacrylate bone cement, and stabilization with pedicle screws. Sacroplasty to treat bone metastases from HCC has been rarely reported in the literature. We describe the case of a patient with vertebral metastases of HCC treated by this approach. A 65-year-old man had undergone a hepatic segmentectomy in 2004. In May 2008, after several weeks of back pain and bed rest, the patient underwent computed tomography and magnetic resonance imaging of the abdominal and pelvic spine, which revealed metastatic lesions in S1-S5 on the right and S1-S2 on the left. Sacroplasty was performed on all lesions without complications. The patient was discharged from the hospital the same day of the procedure. Two months later, he reported pain relief and improvement in walking. Due to the technical feasibility, low complication rate, and immediate relief of symptoms, sacroplasty for HCC metastases of the sacrum may be considered a valid therapeutic option.
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PMID:Sacroplasty in a patient with bone metastases from hepatocellular carcinoma. A case report. 2043 79

HAb18G/CD147, a cancer-associated biomarker, can promote tumor growth, invasion and metastasis. Here, we established a new strategy to express the extracellular domain of HAb18G/CD147 (HAb18GED) by using the FRT/Flp-In recombinase-based site-directed integration system. Two clones expressing HAb18GED were established, and 600 mg HAb18GED was obtained with more than 95% purity. Our results showed that purified HAb18GED exhibited strong activities to stimulate the secretion of pro-MMP2 and MMP-2 and promote the invasion of HCC cells. Overall, our study effectively overcame the difficulty of large-scale HAb18GED preparation and laid a solid foundation for the further studies on structure and functions of HAb18G/CD147.
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PMID:New strategy for large-scale preparation of the extracellular domain of tumor-associated antigen HAb18G/CD147 (HAb18GED). 2086 55

Lack of compensatory or even reduced food intake is frequently observed in weight-losing cancer patients and contributes to increased morbidity and mortality. Our previous work has shown increased transcription factor expression in the hypothalamus and ventral striatum of anorectic rats bearing small tumors. mRNA expression of molecules known to be involved in pathways regulating appetite in these structures was therefore assessed in this study. Given that pain, pro-inflammatory cytokines and metabolic hormones can modify food intake, spinal cord cellular activation patterns and plasma concentrations of cytokines and hormones were also studied. Morris hepatoma 7777 cells injected subcutaneously in Buffalo rats provoked a 10% lower body weight and 15% reduction in food intake compared to free-feeding tumor-free animals 4 weeks later when the tumor represented 1-2% of body mass. No differences in spinal cord activation patterns or plasma concentration of pro-inflammatory cytokines were observed between groups. However, the changes in plasma ghrelin and leptin concentrations found in food-restricted weight-matched rats in comparison to ad libitum-fed animals did not occur in anorectic tumor-bearing animals. Real-time PCR showed that tumor-bearing rats did not display the increase in hypothalamic agouti-related peptide mRNA observed in food-restricted weight-matched animals. In addition, microarray analysis and real-time PCR revealed increased ventral striatal prostaglandin D synthase expression in food-restricted animals compared to anorectic tumor-bearing rats. These findings indicate that blunted hypothalamic AgRP mRNA expression, probably as a consequence of relatively high leptin and low ghrelin concentrations, and reduced ventral striatal prostaglandin D synthesis play a role in maintaining cancer-associated anorexia.
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PMID:Hormonal, hypothalamic and striatal responses to reduced body weight gain are attenuated in anorectic rats bearing small tumors. 2133 29

The role of microRNAs (miRNAs) in human tumorigenesis has been demonstrated by gene profiling and functional studies. In hepatocellular carcinoma (HCC), consistently deregulated miRNAs were identified. Their aberrant expression revealed relations shared with other types of cancer and others unique to HCC, namely the down-regulation of miR-122. Most importantly, functional and molecular studies uncovered mechanisms that linked deregulated miRNAs to cancer-associated pathways, thereby placing their deregulation in a more rational framework. These results improved our knowledge concerning the molecular basis of HCC and helped to increase our understanding about the great clinical potential behind these small molecules. In fact, a number of studies proved that miRNAs may have clinical relevance as bio-pathologic markers for HCC classification, prognostic stratification, early diagnosis or follow-up of patients. Additionally, the demonstration that miRNAs themselves or anti-miRNA oligonucleotides could be successfully used for in vivo modulation of miRNA actions has shown significant potentials in molecularly targeted therapy. In this context, the liver represents an organ of election to test therapeutic possibilities associated with miRNAs.
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PMID:microRNA involvement in hepatocellular carcinoma. 2155 3

The incidence of hepatocellular carcinoma (HCC) is worldwide sharply on the rise and patients with advanced disease carry a poor prognosis. HCC is the sixth most common cancer and the third leading cause of cancer associated deaths in the world. Intra-arterially administered (131)I-Lipiodol is selectively retained by hepatocellular carcinomas, and has been used as a vehicle for delivery of therapeutic agents to these tumours. In this review we focus on the therapeutic indications, usefulness and methods of treatment with 131-Iodine Lipiodol. The effectiveness of (131)I-Lipiodol treatment is proven both in the treatment of HCC with portal thrombosis and also as an adjuvant to surgery after the resection of HCCs. It is at least as effective as chemoembolization and is tolerated much better. Severe liver dysfunction represents theoretic contraindication for radioembolization as well as for TACE. In such cases (131)I-Lipiodol is an alternative therapy option especially in tumours smaller than 6cm.
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PMID:Iodine-131-lipiodol therapy in hepatic tumours. 2166 71


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