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)

A prospective trial was performed in patients with advanced hepatocellular carcinoma to assess the therapeutic efficacy of transcatheter arterial chemotherapy using implanted reservoirs (12 patients) or conventional transcatheter arterial chemotherapy (8 patients). Epirubicin at a dose of 40 mg/m2 was given every month in the former, while epirubicin at a dose of 60 mg/m2 was administered every 3 months in the latter. During the 6 months from the introduction of these therapies, hospitalized periods were shorter and total hospital costs were less in the reservoir group than in the conventional chemotherapy group (p < 0.05 and p < 0.01, respectively). Transcatheter arterial chemotherapy using implanted reservoirs can be carried out on a day-care basis and may be beneficial for the treatment of patients with advanced hepatocellular carcinoma.
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PMID:Treatment for advanced hepatocellular carcinoma by transarterial chemotherapy using reservoirs or one-shot arterial chemotherapy. 937 90

We developed a Hotwire for use in percutaneous transcatheter thermotherapy (PTCT) for local tumor control. The Hotwire has a temperature sensor and a heater, and is inserted into the hepatic artery through a Y-connector and an angiocatheter. It can then warm fluid from the Y-connector to 45 degrees C under electorical control PTCT was performed on liver tumors using 4 mg of MMC and 10 mg Epirubicin. The antitumor effects and indications for PTCT were investigated in patients with unresectable liver tumors, including 3 patients who had hepatocellular carcinoma (HCC) with intraportal invasion and collateral vessels, one patient with liver metastasis of rectal cancer, and two gastric cancer patients. In all patients, tumor marker levels decreased (PIVKA-II; 8.5-->0.9, 2.9-->0.9, AFP; 1154-->753, CEA; 300-->226, TPA; 6319-->4227, 3312-->943), and CRP levels were markedly elevated with tumor fever. The only adverse reaction to PTCT was nausea and vomiting in one female patient. We repeated PTCT 6 times for giant HCC, and performance status was improved (2-->0). In conclusion, PTCT using the Hotwire is useful for treating hypervascular tumors limited to the liver, especially HCC with intraportal invasion and collateral vessels.
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PMID:[Percutaneous transcatheter thermotherapy (PTCT): use of hotwire for local tumor control]. 938 95

Segmental SMANCS Lipiodol TAE (Seg. SMANCS Lp-TAE) using SMANCS was used to treat HCC in 58 patients and was evaluated in comparison with Seg. Lp-TAE using Epirubicin performed in 50 patients with respect to the course of atrophy of the embolized area, recurrence rate and side effects. On serial CT (Lp-CT) performed after TAE, in cases with P type in which the tumor is present in the periphery of the embolized area and showing Type I homogeneous accumulation of Lp within the tumor, the incidence of atrophy in the embolized area including the tumor was high and the recurrence rate was low. Although no significant difference in the recurrence rate was noted between the groups in which SMANCS and EPI were used, there were more cases with marked atrophy and a lower recurrence rate in the former. No difference was found in post-procedural side effects such as fever between the two groups, while hypotension was rarely observed during the procedure in the group in which SMANCS was used and was easily managed with intravenous steroids. The present results suggest that Seg. SMANCS Lp-TAE is an effective local treatment for HCC limited to a subsegment or segment.
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PMID:[Treatment of hepatocellular carcinoma by segmental SMANCS Lipiodol-TAE]. 951 99

Between 1990 and 1997, 227 patients with hepatocellular carcinoma were treated by intrahepatic arterial injection of a Lipiodol-Epirubicin-Mitomycin C emulsion followed by intermittent hepatic artery infusion of Epirubicin, Mitomycin C and 5-FU, employing an implantable subcutaneous infusion port. A catheter was inserted percutaneously into the hepatic artery using the Seldinger technique. Objective remission was induced in 80% of the evaluable patients as evidenced by a decrease in their AFP and PIVKA II levels. These remissions were also confirmed by liver sonogram and CT scan showing decreased tumor volume. Transcatheter oily chemoembolization combined with intermittent hepatic artery infusion chemotherapy seems to be an effective treatment for unresectable hepatocellular carcinoma both for palliation of symptoms as well as prolongation of survival with good quality of life.
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PMID:[Transcatheter oily chemoembolization and intermittent hepatic artery infusion chemotherapy in the management of advanced hepatocellular carcinoma]. 970 3

A 10-center cooperative clinical study with a new formulation of epirubicin hydrochloride injectable solution (Epirubicin-RTU) was conducted in patients with hepatocellular carcinoma. Epirubicin-RTU 60 mg/m2 was injected into the hepatic artery and a three-week drug-free interval followed. Of 15 patients with hepatocellular carcinoma registered in this study, 14 patients were eligible, and they all completed the entire course. The objective was to investigate the safety of treatment with Epirubicin-RTU in 14 eligible patients. The adverse drug reactions frequently observed in these 14 eligible cases were leukopenia, neutropenia, thrombocytopenia, alopecia, and fever. They were all reversible and tolerable. With these results. Epirubicin-RTU was considered to be a safe pharmaceutical product to inject into the hepatic artery.
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PMID:[Results of clinical study with epirubicin hydrochloride injectable solution in hepatoma]. 975 97

New data show that perioperative cytostatic therapy is beneficial in the case of liver transplantation for hepatic cancer. However, it has not been established clearly whether chemotherapy interferes with graft rejection. We therefore studied the interactions between tumor growth and graft rejection, especially with regard to chemotherapy, using a combined tumor/transplantation model. As a tumor model, we used the Novikoff hepatoma, a malignant hepatoma that was injected subcutaneously into the backs of rats. Heterotopic heart grafting served as the transplantation model. In a first step (a), we studied the effect of cytostatic therapy on tumor growth: tumor cells were injected, and in four groups epirubicin, cyclosporine, epirubicin + cyclosporine, and placebo were applied, in corresponding groups, transplantation was additionally performed. Tumor growth was measured and the resected tumors were examined by histology and immunohistology. In a second step (b), we studied the effect of chemotherapy on graft rejection: transplantation was performed and the above-mentioned drugs were applied; in corresponding groups, a solid tumor was additionally induced and resected immediately before transplantation. The results of these procedures were as follows: (a) Epirubicin decreased tumor growth and diminished the volume-increasing effect of cyclosporine significantly. After transplantation, tumor growth was similar. (b) Epirubicin prolonged graft survival significantly, and the combination with cyclosporine had an augmenting effect. In the corresponding groups, graft survival was similar. In conclusions. chemotherapy diminishes the tumor-increasing effect of cyclosporine and does not interfere negatively with graft survival. It might therefore be beneficial after transplantation for malignancy.
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PMID:The efficacy of adjuvant cytostatic therapy after organ transplantation for malignancy: an experimental study with a combined transplantation/tumor model. 1083 50

We report a patient with combined hepatocellular carcinoma and cholangiocarcinoma (HCC-CC) growing into the common bile duct (CBD) and showing obstructive jaundice within 2 years of the onset of the disease. The patient was a 59-year-old Japanese man in whom, at the age of 57 years. a hepatic tumor was discovered by diagnostic imaging during follow-up of hepatitis B surface antigen (HBsAg)-positive liver cirrhosis. The tumor was diagnosed as HCC. Epirubicin was injected twice, intraarterially. The patient then received oral etoposide therapy for the next 14 months. The treatment was initially effective, but approximately 2 years after the hepatic tumor was discovered, local recurrence of the tumor and a tumor thrombus in the CBD were discovered. Although he was treated with percutaneous transhepatic biliary drainage (PTBD), to reduce obstructive jaundice, the jaundice was irreversible and he died of severe hepatic failure. The autopsy findings confirmed that the hepatic tumor was HCC-CC, in which the HCC and CC components expressed alpha-fetoprotein (AFP) and carbohydrate antigen 19-9 (CA19-9), respectively, which accurately reflected the disease process. The underlying mechanism of the growth of HCC-CC into the CBD may differ from the underlying mechanism of the development of icteric-type HCC.
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PMID:Combined hepatocellular carcinoma and cholangiocarcinoma growing into the common bile duct. 1177 13

Human cancers, including hepatocellular carcinoma (HCC), are characterized by a high degree of drug resistance. The multidrug resistance (MDR) transporters MDR1-P-glycoprotein and MRP2 (multidrug-associated protein 2) are expressed in almost 50% of human cancers, including HCCs. In this study, we analyzed the effect of anti-MDR1 ribozymes, especially AFP promoter-driven anti-MDR1 ribozymes, to specifically chemosensitize HCC cells. Epirubicin-selected HB8065/R cells were used as MDR1-P-glycoprotein-overexpressing cells. Adenoviral vectors were constructed to allow an efficient gene transfer of anti-MDR1 ribozyme constructs. AFP promoter-driven anti-MDR1 ribozymes reduced the IC(50) 30-fold for epirubicin in HCC cells, whereas human colorectal cancer cells were unaffected. Target sequences were either the translational start site or codon 196 of the human MDR1 gene. Adenoviral delivery of CMV promoter-driven anti-MDR1 ribozymes resulted in a reduced IC(50) for epirubicin and doxorubicin (60- and 20-fold, respectively). They completely restored chemosensitivity in stably transfected anti-MDR1 ribozyme-expressing HCC cells as well as in HCC cells transduced with adenoviruses expressing wild-type anti-MDR1 ribozymes. Adenoviral delivery of ribozymes was so efficient that chemosensitization of HCC cells could be demonstrated in cell cultures without further selection of transduced cells for single anti-MDR1 ribozyme-expressing HCC cell clones. Northern blots showed a decreased MDR1 mRNA expression, and fluorescence-activated cell sorting (FACS) analysis revealed a significantly reduced expression of MDR1-P-glycoprotein on the cell surface of HB8065/R cells after transduction with the anti-MDR1 ribozymes. In conclusion, our data demonstrate that adenoviral delivery of ribozymes can chemosensitize HCC cells and that chemosensitization can be specifically achieved by ribozymes driven by an AFP promoter directed against human MDR1.
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PMID:Reversal of drug resistance of hepatocellular carcinoma cells by adenoviral delivery of anti-MDR1 ribozymes. 1229 34

Epirubicin HCl is a new anthracycline analog and derivative of doxorubicin. Doxorubicin is a potent anticancer agent, the use of which is limited by its cumulative dose-dependent cardiotoxicity. Epirubicin HCl has more favorable therapeutic index than doxorubicin and possesses less hematologic and cardiac toxicity at comparable doses. Hepatoma G2 cells are a valuable model to study hepatocellular carcinoma and the liver, where drugs are metabolized. The goal of our study was to evaluate the cytotoxic effect of epirubicin HCl on viability of Hep G2 cells measured using the MTT cytotoxicity test. Epirubicin HCl produced a concentration- and time-dependent cytotoxicity to Hep G2 cells. The mechanism of cytotoxicity of epirubicin HCl (IC(50) value of 1.6 mug/ml within 24 h) appeared to involve a production of free radical species since activities of free radical scavenging enzymes (SOD, catalase, Se-dependent GPx) were increased. Addition of SOD prevented cytotoxicity of epirubicin HCl, and also counteracted the apoptosis. DNA fragmentation was determined to evaluate apoptosis. Western blot analysis indicated a decrease in GST-pi expression and increased activity of NADPH-dependent cytochrome P450 reductase which is a major enzyme in the conversion of epirubicin HCl to a free radical. It is proposed that production of reactive oxygen species increased by the treatment with epirubicin HCl can cause lipid peroxidation, which subsequently promotes apoptosis and reduces cell viability. Superoxide dismutase, catalase and glutathione peroxidase must be considered as a part of the intracellular antioxidant defense mechanism of Hep G2 cells against single electron reducing quinone-containing anticancer antibiotics.
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PMID:Epirubicin HCl toxicity in human-liver derived hepatoma G2 cells. 1552 Apr 98

Epirubicin is an antineoplastic agent known as an anthracycline. It acts directly on DNA by blocking its replication and transcription, so apoptosis can be induced for cancer cells. The protein expression of cancer cells will be altered due to the induction of pharmacological action of epirubicin, so it is important to pay attention to the altered profiling of proteins. Here proteomic strategy was applied to the hepatoma cells at subcellular level, comparative proteome analysis of mitochondria and nucleus were conducted between the hepatoma cells administered with epirubicin and the not-administered. Centrifugation was used for the subcellular fractionation, then 2-DE for the separation of proteins, imaging analysis for the diction of expression-altered spots, and MALDI-TOF-MS for the identification of proteins. In total, 15 proteins were found to have altered their expression after the induction of epirubicin, among them, 5 proteins showed up-regulated expression and 10 showed down-regulated expression. These altered proteins are involved in life processes of cells such as energy metabolism, protein biosynthesis, structure of cell skeleton, processing and maturation of mRNA, heat shock of cells and apoptosis.
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PMID:[Proteomic approach to the effect of epirubicin on hepatoma cells at subcellular level]. 1711 50


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