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

1. Epoxide hydrolases form an enzyme family involved in the metabolism of a variety of xenobiotics including cytostatic drugs and carcinogens. Whether human microsomal epoxide hydrolase--one of the main members of the epoxide hydrolase family--is expressed in neoplasia of the liver has been the subject of a controversial discussion. 2. We therefore developed a quantitative immunohistochemical assay and monitored epoxide hydrolase expression in hepatocellular carcinomas (HCC, n = 20), cholangio-cellular carcinomas (CCC, n = 2) and liver metastases (n = 57) of tumours of various origins, and compared the expression intensities and patterns to normal liver tissue. 3. In normal liver tissue microsomal epoxide hydrolase displays expression of the constitutive type with non-zonal staining of all hepatocytes. 4. When using a quantitative immunohistochemical approach statistically significant differences in microsomal epoxide hydrolase expression were observed between normal tissue, hepatocellular carcinoma and liver metastases (mean optical density 2.35, 1.63 and 0.21 respectively, p = 2.9, 6.3 and 18.9). These data indicate differential expression in different types of liver neoplasm. 5. As microsomal epoxide hydrolase is involved in metabolism of different xenobiotics our findings may have implications for tumour progression.
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PMID:Immunohistochemical assessment of human microsomal epoxide hydrolase in primary and secondary liver neoplasm: a quantitative approach. 885 25

In this review, the pharmacokinetic rationale for hepatic arterial drug therapy is discussed, along with techniques that have been developed in order to try to enhance the regional advantage accrued from this route of administration. Clinical trials of hepatic arterial therapy in patients with primary hepatocellular carcinoma and with liver metastases from colorectal carcinoma are discussed. Although clinical response rates are significantly better with regional as compared with systemic therapy, survival is not prolonged. This is mainly due to the development of extrahepatic metastases. A treatment strategy using high dose hepatic arterial 5-fluorouracil (5-FU) infusion with the deliberate aim of achieving maximum tolerated systemic drug levels has entered phase III clinical trial. Monitoring of in vivo tumour pharmacokinetics using 19F magnetic resonance spectroscopy and 18F-5-FU positron emission tomography (PET) demonstrate elegantly how target drug uptake may be assessed. We plan to use PET to monitor intra-tumoral viral transduction and 5-flucytosine conversion rates to active 5-FU in our hepatic arterial pro-drug gene therapy programme soon to enter clinical trial.
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PMID:Intra-hepatic arterial drug delivery. 886 53

Percutaneous ethanol injection (PEI) is a relatively new therapeutic technique for the treatment of liver tumours. PEI is now considered a reliable alternative to surgical resection for cirrhotic patients with a single, small hepatocellular carcinoma (HCC). Intratumoral injection of absolute ethanol, in fact, achieves complete ablation of HCC nodules 3 cm or less in diameter with a high probability. Moreover, PEI is not associated with significant morbidity or mortality and does not damage non-cancerous liver parenchyma. Long-term survival rates of PEI-treated patients were similar to those obtained in matched patients submitted to partial hepatectomy. In large HCC lesions, the anticancer effect of PEI can be significantly enhanced by pretreatment of the tumour with transcatheter arterial chemoembolisation. PEI may also be effectively used to destroy adenomatous hyperplastic nodules in liver cirrhosis, which represent precancerous lesions. The results of PEI in the treatment of liver metastases, in contrast, have been far less encouraging than in the case of HCC, so that PEI is not recommended when other interventional procedures such as radiofrequency electrocautery or interstitial laser photocoagulation are available. Imaging procedures plays a key role in PEI, as they provide a reliable assessment of the therapeutic effect of the procedure.
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PMID:Ethanol injection for the treatment of hepatic tumours. 893 35

There are pharmacologic principles that make regional chemotherapy to the liver a logical treatment strategy. Patients with colorectal liver metastases and hepatocellular carcinoma would appear to be the best candidates for such an approach. Although there are many objective responses to such treatment, survival benefit has not been demonstrated, but new regimens and refined techniques appear to be improving results. Ultimately, regional delivery may be best suited for innovative treatments such as biologicals and gene therapies.
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PMID:Regional chemotherapy approaches for primary and metastatic liver tumors. 901 61

Our objective was to study Gd-EOB-DTPA for the characterization of focal liver lesions by means of dynamic MR imaging. A double-blind and randomized dose-ranging phase-2 clinical trial was performed in 31 patients (liver metastases n = 23, hepatocellular carcinoma n = 4, and hemangioma n = 4) at a field strength of 1.0 Tesla. Gd-EOB-DTPA (Schering AG, Berlin, Germany) was administered as an IV bolus (12.5, 25, or 50 micromol/kg body weight) with dynamic T1-weighted MRI during the distribution and cellular uptake of the contrast agent at multiple time points up to 45 min post contrast. Dynamic changes in tumor signal intensity, tumor-liver contrast, enhancement patterns, side effects, and adverse events were evaluated. Monitoring of vital signs revealed no significant changes during bolus injection of Gd-EOB-DTPA. Liver metastases demonstrated an inhomogeneous uptake of Gd-EOB-DTPA during the distribution phase with a washout effect on delayed images > 3 min and highest tumor-liver contrast 20 and 45 min post contrast. Hepatocellular carcinomas showed prolonged enhancement as compared with metastases and hemangiomas. Hemangiomas exhibited an early peripheral-nodular enhancement with subsequent partial or complete filling, persisting enhancement < 10 min following injection of Gd-EOB-DTPA, and delayed washout as compared with liver metastases. Initial clinical experience suggests that Gd-EOB-DTPA as a bolus injectable hepatobiliary MR contrast agent may offer useful features for the characterization of focal liver lesions.
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PMID:Enhancement characteristics of liver metastases, hepatocellular carcinomas, and hemangiomas with Gd-EOB-DTPA: preliminary results with dynamic MR imaging. 903 30

Nonspecific extracellular gadolinium chelate (NEGd) was prospectively compared with managanese (Mn)-DPDP (Mn) for the detection and characterization of focal liver lesions of various histology. Seventeen patients with known or suspected focal liver lesions underwent NEGd and Mn-enhanced studies at 1.5 T. Study findings were correlated with histology (five patients), computed tomography (CT) examinations (17 patients), and 4- to 13-month imaging follow-up by CT and/or MR (five patients). NEGd studies were performed as serial postcontrast spoiled gradient echo (SGE) sequences, and Mn studies were performed as SGE sequences 15 and 30 min postocontrast and T1-weighted, fat-suppressed spin echo at 16 min. NEGd and Mn images were prospectively interpreted in a separate blinded fashion. Lesion detection and characterization were determined. NEGd and Mn-enhanced images demonstrated 61 and 49 lesions, respectively (p = .1, NS). A total of 60 and 33 lesions were characterized on NEGd and Mn images, respectively, which was significantly different (p = .008). No differences were observed for the detection and characterization of liver metastases; whereas there was a trend for superior detection and characterization for hepatocellular carcinoma with NEGA.
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PMID:Comparison of gadolinium chelates with manganese-DPDP for liver lesion detection and characterization: preliminary results. 906 9

Primary and metastatic liver cancers have a poor prognosis. At present, sonographically guided alcohol injection results in a partial reduction of cancer masses even if severe toxic effects (including pain and bleeding) are always present. For these reasons, a pilot study was started to evaluate the feasibility of an intralesional adoptive immunotherapeutic approach, using lymphokine-activated killer (LAK) cells and recombinant interleukin-2 (rIL-2). Nine patients (one with primary hepatocarcinoma and eight with liver metastases) entered the study. Four cycles of weekly injections of LAK cells (ranging from 2 to 9 x 10(8)) and 10(6) IU rIL-2 were performed percutaneously under ultrasonic guidance. In the same period, 3 x 10(6) IU rIL-2/day, for 24 days, was injected subcutaneously. All patients but one completed the therapy. Side effects were limited to grade 1-2 fever and were mostly related to rIL-2 subcutaneous injections. No patients complained of having pain during intralesional therapy. Two complete responses were detected. One partial response, four stable diseases, and one progressive disease were observed. One patient was not evaluable. These preliminary results suggest that sonographically guided intralesional adoptive immunotherapy of liver tumors is feasible, safe, and could offer promising therapeutic advantages in cancers for which conventional treatment is generally unsatisfactory.
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PMID:Intralesional sonographically guided injections of lymphokine-activated killer cells and recombinant interleukin-2 for the treatment of liver tumors: a pilot study. 908 88

CT is an important technique in liver imaging. To improve the detection of focal liver lesions the use of non-specific, water-soluble contrast media (CM) is mandatory. However, even with use of these CM the sensitivity in tumour detection is low. In the development of liver-specific CM, the majority of the agents have been targeted to the reticuloendothelial system (RES). The clinical use of RES-specific contrast agents has been hampered by frequent adverse reactions, and a new concept whereby the CM is taken up by the hepatocytes has been developed as an alternative. Such a CM is taken up by normal liver parenchyma but not by tumour cells, enhancing the difference between normal and pathological tissue, and therefore improving the diagnostic sensitivity. In the present investigation, FP 736-03 and FP 736-04, two hepatocyte-specific lipid emulsions, have been studied using animal models. In normal liver parenchyma dose-dependent enhancement was found, whereas in tumour tissue of experimental liver metastases and hepatocellular carcinoma, no enhancement was noted. The virtually unchanged attenuation in tumour tissue meant that the liver-to-lesion contrast increased steadily during the observation period. In an attempt to establish the relationship between enhancement and tumour detection, the accumulated doses of FP 736-04 were used. Increasing accuracy in the diagnosis of liver metastases was found up to an enhancement level of 30 HU. A further increase yielded similar detection rates, but a higher proportion of false-positive results. Comparison with iohexol was rendered difficult by the occurrence of image artefacts when this CM was used. However, FP 736-03 proved superior to both native and iohexol-enhanced CT for detection of hepatic metastases. The efficacy of FP 736-04 was also studied in diseased hepatic parenchyma. In cases of fatty liver infiltration, enhancement by FP 736-04 was significantly reduced as compared with normal controls. The degree of enhancement observed in cirrhotic livers did not differ significantly from that in the controls. These preclinical investigations have shown that the hepatocyte-specific lipid emulsions FP 736-03 and FP 736-04 improve the diagnostic accuracy of focal liver lesions as compared to native and water-soluble CM-enhanced CT. FP 736-04 is taken up by diseased liver parenchyma. However, the detection of malignancy in steatotic and cirrhotic livers has not yet been studied with use of this CM.
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PMID:Hepatocyte-specific contrast media for CT. An experimental investigation. 916 54

The high incidence of hepatocellular carcinoma (HCC) in cirrhosis, where previous studies have indicated a severe reduction in several antioxidant vitamin factors, prompted us to compare plasma liposoluble vitamins with tocopherol content in healthy and neoplastic liver tissue in humans. This, with a view to a more positive preventive dietary approach, given the conflicting results obtained by liposoluble vitamin dietary supplementation in different malignancies. Eleven patients with cirrhosis, 18 patients affected by cirrhosis with HCC, and 10 patients with liver metastases (LM) from digestive tract adenocarcinomas were compared with controls who had undergone perlaparoscopic cholecistectomy. Plasma alpha- and beta-carotene, retinol and tocopherol, together with liver tocopherol, from both nonmalignant portions and malignant nodules of the same organ, were determined by high-performance liquid chromatography following a well-assessed technique. The results confirm a trend towards a reduction in circulating carotenoids and tocopherol in cirrhosis and in patients affected by cirrhosis with HCC. Tocopherol content in liver tissue is significantly decreased in cirrhosis (0.26 + 0.03 micromol/g prot., mean + SEM, P < .001) and in cirrhotic areas of the HCC group (0.31 + 0.02, P < .002), with respect to its content in liver specimens of healthy controls (0.46 + 0.03) and in healthy areas of the same organ in patients with LM (0.41 + 0.03). Tocopherol concentration is further reduced by 50% in malignant liver nodules of HCC, with respect to surrounding cirrhotic tissue, whereas in metastatic liver nodules from digestive neoplasms the tocopherol content is almost twice that of healthy surrounding areas. This unpredictable tocopherol behavior in liver specimens, of secondary as opposed to primary malignancies of the liver, affords further insight into the conflicting effects of liposoluble vitamins employed in the chemopreventive treatment of different malignant diseases, where hepatic tocopherol concentration show opposite trends: halved in primary HCC and doubled in LM of digestive adenocarcinomas, with respect to healthy controls.
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PMID:Hepatic tocopherol content in primary hepatocellular carcinoma and liver metastases. 921 53

Primary hepatocellular carcinoma and liver metastases affect several million people each year. The main imaging modalities to detect and assist diagnosis of primary and secondary liver tumours include MR imaging, CT, and US. The value of these techniques is further increased by the use of contrast agents which increase the sensitivity, and sometimes also the specificity, of the investigations. The relative advantages and drawbacks of the different contrast agents and imaging modalities in the detection and characterisation of liver tumours are discussed. Currently there is no consensus amongst investigators as to which is superior, due to the technical complexities and number of combinations possible within each of the different modalities. There continues to be advances in the hardware and software of imaging equipment, as well as a trend to develop new contrast agents with more organ-specificity. These include those targeting the hepatocytes, such as mangafodipir trisodium (MnDPDP, Teslascan), and those with reticuloendothelial cell specificity, such as the superparamagnetic iron oxides. These developments have the potential for making significant contributions to the diagnostic value of imaging procedures and, by reducing the number of investigations necessary to reach a final diagnosis, having a significant and beneficial impact on the pharmaco-economics of patient health care.
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PMID:Liver imaging. Clinical applications and future perspectives. 924 55


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