Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There is growing interest in screening to detect symptomless hepatocellular carcinoma (HCC), which should be easier to treat than symptomatic tumours. Combined alpha-fetoprotein and ultrasound monitoring can detect HCCs of 1 cm, and Lipiodol retention can be detected in tumours smaller than 1 cm. A number of treatment options are available. Surgical resection may be curative in selected patients with a single small tumour, but the cirrhotic patient is left with a diseased liver and the risk of tumour recurrence or death from underlying liver dysfunction. Orthotopic liver transplantation is a rational treatment for patients with decompensating cirrhosis and a small HCC, but it is expensive and necessitates immunosuppression. A variety of targeted or local therapies, either individually or in combination, can be used to treat HCC. These include percutaneous alcohol injection into an HCC, which may be an alternative to surgical resection. Tumour necrosis can be seen after targeted Lipiodol chemotherapy or radiotherapy. Transcatheter arterial embolisation selectively embolises the feeding artery, and can be combined with Lipiodol chemotherapy. Small tumours are thus amenable to treatment, even in patients who cannot have surgery. Screening and treatment for symptomless HCC seems justified, unless controlled trials teach us differently.
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PMID:Treatment of small hepatocellular carcinomas. 135 2

We have shown the in vivo usefulness of a novel chimera tumor necrosis factor (TNF), called rTNF-STH, which was constituted with human thymosin beta 4 and recombinant human TNF-SAM1. Tumor necrosis was induced by intravenous injection of a smaller amount of rTNF-STH (1 x 10(3) U/mouse, 0.67 microgram/mouse) than rTNF-alpha or rTNF-S (1 x 10(4) U/mouse, 2.5-5 micrograms/mouse). Significant antitumor effects of rTNF-STH to Meth A fibrosarcoma, B16 melanoma, MH134 hepatoma, or Lewis lung carcinoma (3LL) were observed by systemic injection of rTNF-STH at the maximum tolerable dose of 1 x 10(4) U/mouse (6.7 micrograms/mouse); this dose did not cause regression of tumors by conventional rTNF-alpha. rTNF-STH showed a significant prolongation of its half-life in serum. The average calculated half-life of the chimera protein is about 110 min, which is 15 times longer than that of original TNF-SAM1 (7.5 min). On the basis of this prolongation of half-life of rTNF-STH and its efficient hemorrhagic necrotic activity, the antitumor effect of rTNF-STH--as compared with that of the known TNF species--is discussed. Findings indicate that use of the chimera protein to alter the N-terminal region of TNF may be a promising approach to obtain molecules that more favorably attack tumors and other diseases than conventional rTNFs.
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PMID:Antitumor activity of a novel chimera tumor necrosis factor (TNF-STH) constructed by connecting rTNF-S with thymosin beta 4 against murine syngeneic tumors. 204 90

The precise cause of the anaemia that is commonly associated with severe pulmonary tuberculosis (PTB) has not been elucidated. The role of erythropoietin (Epo), the central hormone regulating red cell formation, still awaits clarification. We therefore determined serum Epo levels in patients with PTB; group 1, haemoglobin less than 110 g/L, group 2, haemoglobin greater than 110 g/L; group 3, controls, consisted of matched individuals with uncomplicated iron deficiency; group 4, healthy volunteers. Peripheral blood monocytes were obtained from patients with PTB and the controls, cultured, and the supernatant fluid (SNF) harvested. Tumour necrosis factor alpha (TNF alpha) levels were determined in the SNF, which were then added in various dilutions to a hepatocellular carcinoma cell line (HepG2) capable of regulated EPO synthesis in vitro. The influence of this cytokine was defined by the addition of specific neutralising anti-TNF alpha antibodies in this assay system. Patients in group 1 had significantly lower Epo levels (54 + 11 mU/mL) compared with those in group 3 (142 +/- 41 mU/mL) (p < 0.01). Monocyte supernatants from patients in the anaemic PTB group had markedly elevated TNF alpha levels and significantly suppressed Epo output by HepG2 cells in vitro (p < 0.01). This inhibition was consistently abrogated by anti-TNF alpha antibodies. Serum Epo levels were inappropriately low in untreated PTB patients when compared with corresponding haemoglobin levels in iron deficient controls. This blunted response could be ascribed to release of TNF alpha or other cytokines by activated monocytes.
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PMID:Blunted erythropoietin response to anaemia in tuberculosis. 758 43

We investigated the long-term efficacy and the contraindications of single-session percutaneous ethanol injection (PEI) under general anesthesia in hepatocellular carcinoma (HCC). One hundred patients were treated from October, 1991, to April, 1996: 24 patients had a single capsulated HCC, 4.5 to 10 cm phi (group A); 62 had a single infiltrating tumor or multiple lesions (3 to 6), with 10 cm maximum phi (group B); 14 patients were in an advanced stage because of Child class C or of infiltrating tumors with portal thrombosis, with 14 cm lesion maximum phi (group C). Group A patients were treated because they were not operable or refused surgery. Three to 22 injections were performed (mean: 13) depending on tumor size and ethanol spread. The maximum injected volume of ethanol was 190 ml (mean: 57 ml). The procedure took 20 to 50 minutes (mean: 30 minutes). The mean hospital stay was 3.5 days. Tumor necrosis was complete in 58% of encapsulated tumors and > 70% in infiltrating lesions. The greatest lesion with complete post-PEI necrosis was 8.2 cm phi. A transient and variable increase in transaminase, bilirubin, white cell and D-dimer levels and a decrease in red cell, platelet, hemoglobin, fibrinogen and haptoglobin levels were observed. These changes were due to hepatic cell necrosis, hemolysis and focal thrombosis. One death (bleeding esophageal varices in the Child C patient)(1%) and four major complications (one peritoneal bleeding, one liver decompensation, two chemical segmentectomies with pain)(4%) were observed. 1, 2, 3 year survival rates for groups A, B and C were: 80, 63, 63%; 70, 50, 30% and 58, 14 and 0% respectively. In our experience, PEI was an efficacious procedure. The risk conditions are: superficial lesion site with severe coagulation defects, severe portal and/or pulmonary hypertension, esophageal varices at risk of bleeding, cardiac ischemia, advanced cirrhosis.
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PMID:[Single-session alcohol administration for hepatocarcinoma]. 942 44

Replication-competent adenoviruses (Ads) were used for oncolytic virotherapy soon after they were discovered. Recently mutated and genetically engineered Ads have been shown to selectively lyse tumor cells. We have split the human Ad type 5 genome into two defective viruses that complement each other only in certain tumor cells. The genome of one of these vectors, GT5610, contains only the minimal viral elements required in cis for replication and packaging and the E1 viral genes with E1A under the control of the human alpha-fetoprotein promoter. This "controlled" vector has a capacity for 30 kilobases of foreign DNA. The supplemental vector, AdHbeta, contains all adenoviral genes except for E1. Both vectors were designed to carry heterologous reporter genes whose expression could be detected throughout the tumor. Coinfection of hepatocarcinoma cells that have the capacity to transcribe genes under the control of the alpha-fetoprotein promoter leads to cell lysis and copropagation. The oncolytic spread of these complementary vectors in vivo was demonstrated by the intratumoral injection of human hepatocarcinomas xenografted in severe combined immunodeficient (SCID) mice. This system presents safety and gene capacity features that could yield a therapeutic advantage over oncolysis by a single virus.
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PMID:Complementary adenoviral vectors for oncolysis. 1007 60

In this review the usefulness of percutaneous radiofrequency interstitial thermal ablation of liver cancer has been evaluated. The technique has been recently improved by using modified needle electrodes (eg, expandable needle, cooled needle) that allow the ablation of tumors of less than 3.5 cm in diameter in only one session. Tumor necrosis has been shown by imaging techniques such as dynamic or spiral CT, MRI, selective hepatic angiography, ultrasonography-guided fine needle biopsy, and pathologic studies. Both in hepatocellular carcinoma and liver metastases, a complete necrosis has been obtained in more than 80% of the cases. The complication rate has been low without any mortality. In a series of hepatocellular carcinoma followed for a mean time of 23 months, median survival time has been 44 months, whereas recurrence rate was similar to that observed after surgery or ethanol injection. In two small series of metastases, the percentage of disease-free survivors at 1 year ranged from 11 to 66%. In conclusion, radiofrequency interstitial thermal ablation is a safe and effective technique for ablation of liver tumor; however, its precise role in the treatment of liver metastases needs to be defined.
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PMID:Technology for Radiofrequency Thermal Ablation of Liver Tumors. 1040 Nov 46

To study the therapeutic result of hepatic resection for those hepatocellular carcinoma (HCC) shrunked after transcatheter hepatic arterial chemoembolization (TACE) in the patients with unresectable HCC, authors reported 59 patients with HCC. Among the 59 patients, the maximum diameter of the tumor was 5.6 to 20.0 cm prior to the first TACE, mean 9.43 cm. The patients underwent 1 to 6 times of TACE, mean 2.9 times. The tumor diameters were reduced to 3.29 cm prior to operations. The duration between the last TACE treatment and sequential resection varied from 1 to 7 months, mean 2.53 months. Of the 59 patients, 35 patients' serum alpha-fetoprotein (AFP) levels were elevated. AFP levels returned to normal after TACE treatment in 13 patients. Of the patients, liver segmentectomy, combined liver segmentectomy or partial liver resection was performed in 56 patients, left trilobectomy in 2 and left hemihepatectomy in 1. Tumor necrosis ranged from 40% to 100% pathologically and complete tumor necrosis occurred in 9 patients. Of the 13 patients with AFP levels decreased to normal, 9 still had microscopic living tumor foci. The 1-, 3- and 5- year survival rates were 79.7%, 65% and 56%, respectively. These results indicated that TACE treatment can provide chance of tumor resection for those patients with unresectable HCC and good results can be obtained.
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PMID:[Liver resection after transcatheter hepatic arterial chemoembolization for hepatocellular carcinoma and curative effect analysis]. 1067 86

Herpes simplex virus type 1 (HSV-1) replication within tumors can mediate tumor regression (oncolysis). The genetically engineered, HSV-1 mutant rRp450 does not express viral ribonucleotide reductase and is therefore replication conditional. During the course of infection, rRp450 expresses the cytochrome P450 transgene and HSV-1 thymidine kinase gene, thereby enabling it to bioactivate the prodrugs cyclophosphamide and ganciclovir, respectively. rRp450 replication in hepatocellular carcinoma (HCC) cells is cytotoxic and liberates progeny virion that infect adjacent tumor cells. rRp450-mediated oncolysis is enhanced in the presence of cyclophosphamide, whereas it is inhibited in the presence of ganciclovir. As a consequence of defective viral ribonucleotide reductase expression, the yield of rRp450 progeny virions from infection of HCC cells is 3 to 4 log orders greater than that from infection of normal hepatocytes. This is associated with dramatic tumor reduction of diffuse HCC after a single intravascular administration of rRp450. rRp450 holds the promise of the dual therapeutic benefit of selective oncolysis and P450 transgene delivery.
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PMID:Oncolysis of diffuse hepatocellular carcinoma by intravascular administration of a replication-competent, genetically engineered herpesvirus. 1085 Apr 15

A transplantable human hepatoma model, the QGY-9204, was used in this study. The growth kinetics of hepatoma in nude mice were compared after injection of parvovirus H-1 into the tumor growth. Significant difference in growth curves were seen between injected groups with H-1 dosages of 5 x 10(7) PFU and 5 x 10(8) PFU and that of control. It indicated that parvovirus H-1 was capable of suppressing the growth of human hepatoma. Previous studies showed H-1 is oncotropic, oncosuppressive and oncolytic. For histological, ultrastructural and histochemical examinations, transplantable hepatomas were taken at different time interval post H-1 (1 x 10(8) PFU per tumor growth) injection. For H-1 DNA amplification and H-1 nonstructural protein expression, PCR and ABC approach in hepatoma paraffin sections were used. The H-1 treated groups exhibited obvious signs of necrosis. It started on 3rd day post infection (3 d.p.i.) and the area of necrosis enlarged consecutively on 7 d.p.i., 10 d.p.i. and 14 d.p.i., but none was seen in saline-injected group even on 14 d.p.i. H-1 virions were also detected in the damaged tumor cells with numerous vacuoles in cytoplasm. Specific band (908 bp) of H-1 DNA and ABC immunostaining indicated H-1 DNA replication and NS-1 expression in tumors of treated groups, their time course was well in accordance with that process of necrosis. These results suggest that parvovirus H-1 promotes tumor necrosis by its DNA replication and cytotoxic NS-1 protein expression, and thus, it inhibits hepatoma growth and induces oncosuppression and oncolysis.
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PMID:[Inhibition of parvovirus H-1 on transplantable human hepatoma and its histological and histobiochemical studies]. 1103 20

Tumour necrosis factor (TNF)-alpha contributes to the pathogenesis of many inflammatory diseases. Recombinant soluble TNF receptor fusion proteins (sTNFR:Ig) are potent TNF antagonists, both in vitro and in vivo. The concentration of serum amyloid A (SAA) increases by up to 1000-fold during inflammation, largely owing to cytokine-driven transcriptional upregulation. A reporter plasmid, comprising the proximal 0.7 kb of the human SAA2 promoter fused to a luciferase gene, was used in transient transfection experiments in human HepG2 hepatoma cells to assess the quantitative and qualitative TNF antagonist properties of a construct in which sTNFR:Ig synthesis is under the control of a chimera of the SAA2 promoter and a tat/HIV element. The SAA2-tat/HIV-sTNFR:Ig construct retained the fine-tuned cytokine responsiveness of the SAA2 promoter, while exhibiting the quantitatively enhanced level of protein expression conferred by the tat/HIV element. It produced a biologically significant TNF inhibition that was at least as strong as that achieved using a CMV promoter-driven sTNFR:Ig construct. There was a dose- and time-dependent relationship between the pro-inflammatory cytokine used, and the generation of TNF antagonist activity by SAA2-tat/HIV-sTNFR:Ig. Although sTNFR:Ig protein can be induced by either TNF-alpha or interleukin (IL)-1beta, its antagonist activity is limited to the former cytokine. The SAA2-tat/HIV-sTNFR:Ig construct, and derivatives thereof, may therefore be ideally suited to gene therapy applications that require the local production of potent and specific immune modifiers only when there is active pathology. It may consequently be of particular use in the future treatment of diseases such as rheumatoid arthritis.
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PMID:In vitro evaluation of an enhanced human serum amyloid A (SAA2) promoter-regulated soluble TNF receptor fusion protein for anti-inflammatory gene therapy. 1142 7


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