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)

P-glycoprotein is a plasma-membrane glycoprotein involved in multidrug resistance. P-glycoprotein overexpression has been demonstrated to occur in tumor cells after cytotoxic drug exposure, but also in some cancers including hepatocellular carcinomas before any chemotherapeutic treatment. In order to better analyze this constitutive type of tumoral drug resistance, we have investigated P-glycoprotein expression and function in rat liver tumors induced experimentally by administration of diethylnitrosamine and in two cell clones derived from one of these tumors designated as RHC1 and RHC2. High levels of P-glycoprotein mRNAs were found in both liver tumor samples and the two hepatoma cell clones as assessed by Northern blotting; both RHC1 and RHC2 cells displayed altered liver functions commonly observed in rat hepatoma cells, particularly the decreased expression of albumin and overexpression of the fetal glutathione S-transferase 7-7. The use of specific multidrug resistance (mdr) probes revealed a major induction of the mdr1 gene in liver tumor samples while RHC1 and RHC2 cells expressed both mdr1 and mdr3 genes without displaying a major alteration in the number of mdr gene copies as assessed by Southern blotting. High amounts of P-glycoprotein were also demonstrated in RHC1 and RHC2 cells by Western blotting. These cells were strongly resistant to doxorubicin and vinblastine, two anticancer drugs transported by P-glycoprotein. Doxorubicin intracellular retention was low in RHC1 and RHC2 cells, but was strongly enhanced in the presence of verapamil, a known modulator agent of P-glycoprotein; low retention appeared to occur via a drug efflux mechanism, indicating that P-glycoprotein was fully active. These results show that rat hepatoma cells can display elevated levels of functional P-glycoprotein without any prior cytotoxic drug selection and suggest that these cells represent a useful model for analyzing P-glycoprotein regulation in intrinsically clinical drug-resistant cancers.
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PMID:Constitutive expression of functional P-glycoprotein in rat hepatoma cells. 790 26

To study the effect of bile acids on P-glycoprotein-mediated drug transport, we performed experiments using multidrug resistant cells and rat canalicular membrane vesicles. Cellular accumulation and efflux of rhodamine 123 were measured in drug-resistant cells by means of computerized quantitative image analysis and fluorescence microscopy. ATP-dependent [3H]daunomycin transport was studied by means of rapid filtration in canalicular membrane vesicles prepared from normal rats. Doxorubicin-sensitive (PSI-2) and -resistant (PN1A) 3T3 cells and human-derived hepatocellular carcinoma doxorubicin-sensitive and -resistant cells were used. Taurochenodeoxycholate and glycochenodeoxycholate, taurolithocholate and ursodeoxycholate (50 to 200 mumol/L) inhibited rhodamine 123 and [3H]daunomycin transport in multidrug-resistant cells and canalicular membrane vesicles, respectively, whereas taurocholate, taurodeoxycholate and tauroursodeoxycholate did not. Primary and secondary unconjugated bile acids had no effect. These results reveal that taurolithocholate, taurochenodeoxycholate and glycochenodeoxycholate and ursodeoxycholate inhibit P-glycoprotein-mediated drug transport function in multidrug resistant cell lines and in canalicular membrane vesicles. These results suggest possible interaction between P-glycoprotein function and bile acids in cholestasis and after treatment of patients with ursodeoxycholic or chenodeoxycholic acid.
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PMID:Bile acid inhibition of P-glycoprotein-mediated transport in multidrug-resistant cells and rat liver canalicular membrane vesicles. 791 87

In this paper we report the results we obtained after chemoembolization in 46 patients with HCC in cirrhosis. Chemoembolization is performed by introducing, through an angiographic catheter placed after the origin of the gastroduodenal artery, 20 mg of Doxorubicin Chlorhydrate mixed with 20 ml of Lipiodol and with 10 ml of contrast agent followed by embolization with Spongostan. Chemoembolization results were assessed comparing site, size and local spread of the tumor, hepatic compromission (according to Child's classification) and number of chemoembolization maneuvers with survival in each patient. Overall survival rates are 95.7% at 6 months, 88.5% at 12 months, 60% at 18 months, 36.4% at 24 and 31.8% at 30 months. The best responses were obtained with lesions smaller than 5 cm (100% survival at 6 months, 91.7% at 12 months, 71.4% at 18 and 42.8% at 24 months). Other factors favoring good treatment response were a single lesion (92.9% at 6 months, 91.7% at 12 months, 71.4% at 18 and 42.8% at 24 months), at least 3 cycles of chemoembolization (100% at 6 months, 90% at 12 months, 85.7% at 18 and 42.8% at 24 months) and a low degree of hepatic compromission (Child A and B rather than Child C; in the latter group the survival rates were 75% a 6 months and 0% at 12 months). In conclusion, chemoembolization proves to be the treatment of choice in the HCC patients who cannot undergo surgery.
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PMID:[Survival in 46 patients with hepatocarcinoma treated by chemoembolization]. 793 27

By administering an excessive amount of iodized oil via the hepatic artery, anticancer drugs in the iodized oil flow into the portal vein through the arterioportal communication. This phenomenon permits chemotherapy against extracapsular infiltration by a hepatocellular carcinoma (HCC) nourished by the portal blood flow. From May 1983 through July 1992, 240 cases of HCC underwent transcatheter arterioportal chemoembolization (TAPCE) with more than 5 ml of iodized oil (mean, 15 ml) in our hospital. In all, 32 patients survived for more than 3 years, and the factors favoring the efficacy of TAPCE therapy were investigated. Doxorubicin (mean, 46 mg) was given to 31 patients and 20 mg mitomycin C was given to 1 patient. The patients included one Stage 1 case, 13 Stage 2 cases, 17 Stage 3 cases, and one Stage 4 case. The mean tumor size was 5.0 cm, and portal invasion was suggested in 8 cases by angiography. The tumors were divided into 5 types: 13 cases of the single nodular type (SN), 7 cases of the single nodular type with proliferation (SN-P), 3 cases of the multinodular fused type (MN-F), 5 cases of the multinodular type (MN), and 4 cases of the massive type. A complication of liver dysfunction was detected in 14 cases, and half of them were Child's class C. In all, 7 patients underwent hepatectomy and 6 received percutaneous ethanol injection after TAPCE. The treated area of TAPCE was classified as segmental, lobar, or total. Segmental and lobar administration of TAPCE yielded statistically effective results, and their tumor response rate was 86%. All of the MN-F and massive types showed a good tumor response. The incidence of intrahepatic distant metastasis was higher in the localized TAPCE group than in the total TAPCE group. Segmental and lobar TAPCE should be applied for localized infiltrating HCCs, even in cases associated with liver cirrhosis, but these methods have a limited capacity to prevent distant intrahepatic metastasis.
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PMID:Effective cases of transcatheter arterioportal chemoembolization with high-dose iodized oil for hepatocellular carcinoma. 813 86

The Cooperative Study Group conducted a study to assess the therapeutic effects of chemoembolization in patients with advanced hepatocellular carcinoma (HCC) using either epirubicin hydrochloride (FARM) or doxorubicin hydrochloride (ADR). A total of 77 patients were enrolled in this study and randomized into 2 groups: 39 patients were treated with a FARM solution as the material for Lipiodol-transcatheter arterial embolization (TAE; FARM group), and 38 patients were treated with an ADR solution as the material for L-TAE (ADR group). For the FARM group, the 1-year survival rate was 69.9% and the 2-year survival rate was 44.5%. For the ADR group, the corresponding survival rates were 74.7% and 44.0%. The differences among the above figures were not statistically significant. As side effects, fever, nausea, and generalized fatigue occurred at almost the same frequencies in the two groups. Changes detected in the liver function and the peripheral blood cell count in both groups were not severe. There was no significant difference between the toxic effects observed in the two groups. In conclusion, there was no significant difference in therapeutic efficacy between the FARM and ADR groups.
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PMID:Prospective and randomized controlled study of chemoembolization therapy in patients with advanced hepatocellular carcinoma. Cooperative Study Group for Liver Cancer Treatment in Shikoku area. 813 92

A 46-year-old male with unresectable hepatocellular carcinoma (HCC) comprised of severe liver dysfunction was treated by intra-arterial infusion chemotherapy through an implantable reservoir. During 39 months, a total amount of THP-ADR 420 mg, ADR 70 mg and CDDP 350 mg was infused. Through the therapy, the tumor size on the lateral segment was well controlled, and serum AFP and PIVKA-II levels were also lowered. No severe side effect was observed. The patient was treated on an outpatient basis, and a good quality of life during therapy was maintained. This case suggests that THP-ADR may play an important role in a combined intraarterial chemotherapy for advanced HCC.
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PMID:[A case of hepatocellular carcinoma treated by intra-arterial infusion chemotherapy using THP-adriamycin]. 875 11

Doxorubicin was acylated with estrone 3-hemisuccinate. The modified derivative exhibited high antiproliferative activity in vitro toward cell cultures of the MCF-7 human mammary adenocarcinoma and HepG2 human hepatoma.
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PMID:[Synthesis and antiproliferative activity of a novel N-acyl derivative of doxorubicin]. 1038 42

Chemotherapy with cytostatic and cytotoxic drugs is the main treatment modality for disseminated cancer. However, despite initial clinical responses seen in certain histotypes, such as small cell lung cancer, relapses mostly occur with chemoresistant phenotypes. In order to prolong the relapse-free period, a combination of chemo- and immunotherapy might offer a new treatment strategy. Here, we have tested our hypothesis that complement activation, induced by monoclonal antibodies, in combination with cytostatic drugs may result in additive cytotoxicity in vitro. Doxorubicin, cisplatinum and etoposide were tested in combination with human complement and a murine monoclonal antibody (MAb F12) directed against the tumor-associated ganglioside antigen fucosyl GM1 on a rat hepatoma (H4-II-E) cell line which was used as tumor model. Using the MTT assay to measure cell survival, supra-additive (i.e. synergistic) cytotoxic effects were seen with each of the cytostatic drugs, the strongest being observed with doxorubicin. These results show promise for further research exploring possible prognostically favorable interactions between cytostatic drugs and monoclonal antibodies in the treatment of cancer.
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PMID:Supra-additive cytotoxic effects of a combination of cytostatic drugs and antibody-induced complement activation on tumor cells in vitro. 1112 82

Sendai F-virosomes, a novel type of liposome with reconstituted Sendai F-proteins, have been tested as a delivery system for various bioactive materials. However, encapsulation limitations and difficulties in controlling their constituents were drawbacks for further application to therapeutic purposes. We have tried to control virosomal constituents and have enhanced drug encapsulation efficiency into the virosomes. In vitro cytotoxicity of doxorubicin encapsulated in the F-virosomes were compared with free doxorubicin and doxorubicin in conventional liposomes. The F-virosomes were spontaneously prepared by detergent dialysis, a reconstitution process of Sendai F-proteins into liposomes. The reconstitution density of F-proteins affected the vesicle size of virosomes prepared by detergent dialysis; the larger amount of F-proteins made a smaller size of virosomes. There was little variation of size with time at physiological conditions, whilst the vesicle size of virosomes increased at acidic storage conditions (pH 5.5). Doxorubicin encapsulated in the F-virosomes exhibited a lower IC50 against B16BL6 mouse melanoma cells and Chang human hepatocarcinoma cells than that in conventional liposomes. The F-virosomes also exhibited higher cellular uptake than conventional liposomes. Addition of dioleoylphophatidylethanolamine, a fusogenic phospholipid, into the F-virosome further increased the cellular uptake as well as in vitro cytotoxicity. These types of virosome formulations can be clinically applicable as versatile vesicles for the efficient delivery of various therapeutic drugs, including genetic materials.
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PMID:Enhanced cytotoxicity of doxorubicin encapsulated in liposomes with reconstituted Sendai F-proteins. 1142 72

Doxorubicin (DOX) was coupled to human low density lipoprotein (LDL) to form a complex (LDL-DOX). When injected into mice, LDL-DOX was more accumulated in liver than free DOX. In contrast, LDL-DOX was less accumulated in heart than free DOX. In in vitro studies on human hepatoma (HepG2) cells, although the cellular uptake of LDL-DOX was higher than that of DOX, the anti-proliferative effect of LDL-DOX on these tumor cells was smaller than that of LDL. However, when LDL-DOX or DOX was administered to nude mice bearing HepG2 cells implanted on the shoulder, the anti-proliferative effects on the tumor cells of both drugs were similar. Histological analyses indicated that organization of myocardial filaments was disrupted and vacuolization was observed in DOX-treated group when compared with control group whereas LDL-DOX-treatment did not exhibit any damage in the host's heart. Enzymatic analyses also demonstrated that plasma lactate dehydrogenase activity, which is a common indicator of heart damage, was elevated in DOX-treated group when compared with control group whereas the activity of this enzyme was unchanged in LDL-DOX-treated group. The results in present study indicate that LDL can be used as a targeted carrier for DOX because LDL-DOX can exhibit similar anti-proliferative effect as DOX on tumor but reduce the DOX-induced cardiotoxicity in the host.
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PMID:Low density lipoprotein as a targeted carrier for doxorubicin in nude mice bearing human hepatoma HepG2 cells. 1181 3


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