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)

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

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

Overexpression of the trans-membrane drug efflux pump P-glycoprotein is one of the major mechanisms by which cancer cells develop multidrug resistance. We demonstrated previously that noncytotoxic doses of various genotoxic chemicals, particularly DNA cross-linking agents, preferentially altered expression of inducible genes. These effects occurred principally at the transcriptional level and were closely correlated temporally with DNA damage. Because the mdr1 gene coding for P-glycoprotein has been reported to be highly inducible, we were interested in the effects of genotoxic cancer chemotherapy agents on its expression. We report that the DNA cross-linking agent mitomycin C significantly suppressed mRNA and protein expression of P-glycoprotein and decreased the rate of drug efflux. Mitomycin C pretreatment also significantly increased the sensitivity of cancer cells to subsequent killing by the P-glycoprotein substrate doxorubicin, decreasing the ED50 by 5- to 10-fold. Suppression of P-glycoprotein expression was also observed with subtoxic doses of the DNA cross-linking agents cisplatin, BMS181174, and chromium(VI). These effects occurred in both human and rodent cell lines; in cell lines derived from colon, breast, leukemia, neuroblastoma, and hepatoma tumors; and under both monolayer and "spheroid" culture conditions. These results suggest the basis for novel clinical cancer chemotherapy regimens aimed at drug-resistant tumors, in which a sub-chemotherapeutic dose of a DNA cross-linking agent is used to modulate the multidrug resistance phenotype prior to treatment with a second cytotoxic agent.
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PMID:Suppression of P-glycoprotein expression and multidrug resistance by DNA cross-linking agents. 981 17

There are conflicting results for experiments aimed at determining whether anticancer drug therapy of human hepatocellular carcinoma prolongs the survival rate effectively. The purpose of this study was to assess the effect of low concentrations of doxorubicin, mitomycin C, and ethanol on cell replication (cell number and proliferation), and cell apoptosis of cultured human hepatocellular carcinoma (Hep-G2) cells. After 1 day of exposure doxorubicin inhibited cell replication initially by 72%, but a partial recovery of the cell number was observed. Mitomycin C inhibited to the same extent but without recovery. Ethanol reduced the cell number even further, the maximum inhibition (12 days after exposure) being 96.4%. After 3 days of exposure all three agents stopped cell replication at a level of 2%-4% of the control (P < 0.001). Cell apoptosis was activated most strikingly by mitomycin C (5 microg/ml) after 1 day of exposure and by ethanol (150 microl/ml) after 3 days of exposure. Two-way repeated-measures analysis of variance showed statistically significant differences, with ethanol being the most significant followed by mitomycin C doxorubicin, and the control (P < 0.01). Thus, a low dose of ethanol combined with an exposure time of up to 3 days appears to be an effective regimen to control growth of human hepatocellular carcinoma cells in vitro. The strong induction of apoptosis by ethanol might be of additional benefit for a local application in vivo.
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PMID:Effects of doxorubicin, mitomycin C, and ethanol on Hep-G2 cells in vitro. 1003 71

Transcatheter arterial chemo-embolization (TACE) using degradable starch microspheres (DSM) was performed for multiple recurrence after hepatectomy in a patient with cholangiocarcinoma. The patient was a 68-year-man. He received treatment for hepatitis type C starting in 1996 at a nearby hospital. In November 1997, an increased AFP level was noted and a CT scan of the abdomen revealed an abnormal shadow in the liver. On May 21, 1998, imaging results led to the diagnosis of cholangiocarcinoma or a mixed type of hepatocellular carcinoma with cholangioma. Hepatic S7 sub-sequential resection was performed. The lesion was found to be a tumor-forming type, measuring 2.2 x 2.0 cm in diameter, diagnosed histopathologically as cholangiocarcinoma, tw (-), but Stage III since a nodule suggesting intrahepatic metastasis was noted in the cut surface of the resected liver. CT scan after a month revealed multiple metastatic lesions in the liver. TACE was performed by administering 450 mg of DSM, 10 mg of MMC and 30 mg of FARM, given in three divided doses on October 30, 1998, and February 9, 1999, according to Seldinger's method. A CT scan on January 31, 2000 revealed nearly complete remission of the hepatic SOL. Accordingly, TACE was considered to be useful therapy in combination with DSM, MMC and FARM for intrahepatic recurrence of cholangiocarcinoma.
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PMID:[Transcatheter arterial chemo-embolization using degradable starch microspheres (DSM) markedly effective for post-hepatectomy intra-hepatic recurrence in a patient with cholangioma]. 1108 48

A 73-year old man with multiple hepatocellular carcinomas underwent 4 transarterial chemoembolizations, but a tumor thrombus appeared in the left portal vein. The tumor sizes in segments 4 and 5 were 4.0 cm and 2.4 cm, respectively. The serum levels of AFP and PIVKA-II were 14,991 ng/ml and 15,944 mAU/ml, respectively. The tumor was 5-FU palpable in the epigastric region. Four ml of SMANCS and 4 ml of Lipiodol were injected to proper hepatic artery using the Seldinger technique. In addition, epirubicin (20 mg), MMC (4 mg) and Lipiodoi (2 ml) were injected into a proper hepatic artery via a reservoir every 3 weeks. The tumor was not palpable, and the tumor markers were markedly reduced after 2 months. The evaluation of response to the treatment was a partial response 3 months and 6 months later. Chemo-lipiodolization was very useful for advanced hepatocellular carcinoma with portal vein thrombus.
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PMID:[A case report of hepatocellular carcinoma with portal thrombus responding to hepatic arterial infusion chemo-lipiodolization]. 1248 79

The hepatic artery-embolizing effect of degradable starch microspheres (DSM) was assessed by dynamic CT scanning soon after embolization in patients with malignant hepatic tumors. Using the Seldinger method, DSM with a mixture of contrast medium, MMC, ADM or Epi-ADM was manually injected. The subjects were 32 patients with metastatic carcinoma of the liver (62 treatments) and 15 patients with hepatocellular carcinoma(19 treatments) (47 patients received 81 treatments in all). Dynamic CT scanning was performed within 2 weeks of each embolization procedure, and the percent reduction in the area visualized (necrotic effect) was calculated to assess the efficacy of embolization. The necrotic effect of embolization was classified as CR, PR, NC, and PD after 9, 41, 10, and 2 treatments, respectively, in the patients with metastatic carcinoma of the liver and after 4, 6, 6, and 3 treatments, respectively, in the patients with hepatocellular carcinoma. Although there was no patient in whom the tumor showed 50% or more reduction, the contrast enhanced area showed 50% or more decrease in 60 out of 81 treatments. Therefore, blocking of blood flow seemed to contribute more to the response than enhancement of the efficacy of the anticancer agents. Adverse reactions were all transient and controllable. Based on our results, intra-arterial chemotherapy plus DSM embolization seems to be useful for treating malignant hepatic tumors.
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PMID:[Early effect of intra-arterial chemotherapy combined with degradable starch microspheres for malignant hepatic tumors]. 1255 9

Nineteen patients with far advanced hepatocellular carcinoma received transarterial hepatic chemotherapy. Twelve patients were Child-Pugh A, 2 were B, and 2 were C. Seventeen patients had portal vein thrombus, and 2 patients had extra-hepatic metastasis. Among the 19 patients, 13 received low-dose CDDP and 5-FU, and 5-FU with interferon was performed in 2. Lipiodol chemotherapy with epirubicin and MMC was performed after first-line chemotherapy, following the evaluation of the progressive disease. The 1- and 3-year survival rates in all cases were 42.5% and 18.2%, respectively. Of the 18 patients evaluated for response, 1 showed complete response, 2 showed partial responses, 8 had stable disease, and 7 progressed. Median survival time of CR, PR and SD patients was 14.2 months. A multivariate analysis identified CLIP score and therapeutic effect as independent predictors for mortality. It is concluded that transarterial hepatic chemotherapy was very useful for far advanced hepatocellular carcinoma.
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PMID:[Long-term outcome of advanced hepatocellular carcinoma that received transarterial hepatic chemotherapy]. 1461 68

Caspase-8 is frequently mutated or silenced in several tumors including hepatocellular carcinomas (HCC) thereby potentially contributing to chemoresistance. The aim of our present study was to evaluate if chemotherapeutic drugs may mediate their effects through up-regulation of caspase-8 gene transcription. Huh7 hepatoma cells were transfected with a caspase-8 promoter construct fused to a luciferase reporter gene followed by stimulation with a subset of different chemotherapeutic drugs. Several drugs slightly induced caspase-8 promoter activity. However, strong caspase-8 promoter induction was found after Mitomycin C (MMC) treatment and this correlated with an increase in endogenous caspase-8 mRNA expression. Further molecular analysis demonstrated that MMC controls caspase-8 transcription via a c-jun/AP1 site located in the promoter in close proximity to the transcription start site. Inactivation of this c-jun/AP1 site using a dominant-negative c-jun adenovirus or site-directed mutagenesis inhibited MMC-dependent promoter induction. MMC treatment resulted in higher caspase-8 enzymatic activity and apoptosis and could be synergistically enhanced by co-stimulation with interferon-alpha (IFNalpha) via independent transcriptional mechanisms. In summary MMC controls caspase-8 expression via a c-jun/AP1 element in its promoter region. MMC-induced up-regulation of caspase-8 triggers apoptosis in target cells which can be further enhanced by IFNalpha. Therefore these findings also provide a potential new therapeutic approach to treat cancer cells.
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PMID:Molecular mechanism of Mitomycin C-dependent caspase-8 regulation: implications for apoptosis and synergism with interferon-alpha signalling. 1792 91

This study investigated the inhibitory effect of the extract of fungi of Huaier (EFH) on the growth of hepatocellular carcinoma (HCC) cells. Hep-G2 cells, a human HCC cell line, were cultured in DMEM containing 10% fetal bovine serum and treated with EFH of different concentrations (1, 2, 4, 8 mg/mL) for 24, 48 and 72 h respectively. The apoptosis rate of the cells was flow cytometrically measured. Thirty-six tumor-bearing New Zealand rabbits were randomly divided into 3 groups: group A (control group), in which the rabbits were infused with 0.2 mL/kg normal saline via the hepatic artery; group B (transhepatic artery chemoembolization [TACE] group), in which the rabbits were given lipiodol at 0.2 mL/kg plus MMC at 0.5 mg/kg via the hepatic artery; group C (TACE+EFH group), in which EFH (500 mg/kg) were orally administered after TACE. Two weeks after TACE, the rabbits were sacrificed and the implanted tumors were sampled. The tumor volume and the necrosis rate were determined. The tumor tissues were immunohistochemically detected for the expressions of factor VIII, VEGF, P53, Bax and Bcl-2. The microvessel density (MVD) was calculated by counting the factor VIII-positive endothelial cells. Our results showed that after treatment with EFH, the apoptosis rate of Hep-G2 cells was enhanced in a concentration- and time-dependent manner. Two weeks after the treatment, the average tumor volume, the necrosis rate and the growth rate of the implanted tumor in group C were significantly different from those in groups A and B (P<0.05). MVD and VEGF expressions were significantly decreased in the group C when compared with those in groups B (P<0.05 for all). The Bax expression was weakest in group A and strongest in group C. The expressions of P53 and Bcl-2 were minimal in group C and maximal in group A. There were significant differences in the expressions of P53, Bax and Bcl-2 among the 3 groups (P<0.05 for all) and there was significant difference between group B and group C (P<0.05). It was concluded that EFH could suppress not only the growth of HCC cells but also tumor angiogenesis and it can induce the apoptosis of HCC cells. EFH serves as an alternative for the treatment of HCC.
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PMID:Inhibitory effect of extract of fungi of Huaier on hepatocellular carcinoma cells. 1939 4


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