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)

Doxorubicin (60 mg/m2 at 3-weekly intervals to a maximum total of 550 mg/m2) induced clinical remission in 14 (32%) of 44 patients with hepatocellular carcinoma. In 3 of those who responded, hepatic arteriography showed clearing of the previously extensive tumour circulation, and in a 4th there was disappearance of the tumour on serial ultrasound examinations. A fall in serum-alpha-fetoprotein level after the initial injection of doxorubicin predicted a favourable clinical response, whereas the level continued to rise in patients who did not respond.
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PMID:Induction of remission in hepatocellular carcinoma with doxorubicin. 7 32

A retrospective analysis of 35 stage IV HCC (26 IV-A case and 9 IV-B cases) which underwent reduction surgery from 1983 suggested a possibility to extend their survival period by decrease in their tumor-mass and subsequent immunochemotherapy for improvement of their depressed immunity. Their operability depended on the clinical stage of accompanying liver cirrhosis and extent of distant organ metastasis. It is of first importance for reduction surgery to select intrahepatic multiple tumors, slow-growing and not rapidly to induce distant organ metastases, among them. Intrahepatic tumors arising from multicentric origins were found in 42% in IV-A cases but 0% in IV-B. DNA ploidy analysis of the multicentric tumors in 8 cases did not show any clear indication of resectable tumors according to DNA index. The present immunochemotherapy is composed of a continuous infusion of IL2 and intermittent one-shot injections of 10mg ADR to the remnant liver by using subcutaneously implanted pump. In patients who could enhance peripheral NK and LAK activities by the immunotherapy, decreases in intra- and extra- hepatic tumors were observed. The 2 year-survival rate was 49% in IV-A, but only one case who is receiving the immunotherapy is surviving over 2 years in IV-B.
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PMID:[Significance of reduction surgery for stage IV hepatocellular carcinoma (HCC) and postoperative immunochemotherapy for extension of survival period]. 165 92

Antitumor effect of TNF has been demonstrated to be increased with some kinds of anticancer agents. We reported antitumor effect of hepatic endogenous TNF induced with gamma-IFN and OK-432 for hepatocellular carcinoma (HCC). To increase antitumor effect of transcatheter arterial embolization (TAE), hepatic arterial chemoembolization was performed with a mixture of gamma-IFN, OK-432 and gelatin sponge following a mixture of Doxorubicin and iodized oil (LPO) on the first time. Serum alpha-fetoprotein decreased from 18,903 ng/ml to 470 ng/ml but elevated three months after these procedures. Following the above procedure, hepatic arterial embolization with a mixture of gelatin sponge and Actinomycin D as an inhibitor of RNA was given the second time. Serum alpha-fetoprotein decreased under 5 ng/ml and computed tomography revealed decreased tumor size and low density area following this second procedure. Hepatic arterial chemoembolization with a mixture of hepatic induction of endogenous TNF and anticancer agents may well be beneficial for survival of patient with HCC.
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PMID:[Chemoembolization combined with hepatic arterial induction of endogenous TNF and anticancer agents for hepatocellular carcinoma--a case report]. 216 47

The property of selective deposition of oily contrast medium, Lipiodol (LPD), in tumor tissue was utilized for targetting intraarterial infusion chemotherapy for hepatic cancers. For this therapy anti-cancer agents need to be suspended in LPD. In this report the new suspension device using ultrasonificator attached with Cuphorn was studied. Doxorubicin (Dx) was stable to ultrasonification for 1 hour. Ten mg/ml of Dx was mixed with LPD and this mixture was treated 2 times for 5 minutes with the ultrasonification method. This procedure was simple and sterile, as the commercially used Dx vials into which LPD was injected were set in the Cuphorn and ultrasonificated just as sealed. Microscopic examination of the suspension showed uniform dispersion of Dx particles without formation of aggregates. Dx particles were finely and regularly fragmented. In vitro the suspensions showed a gradual release of Dx from LPD to water phase. In one case with hepatocellular carcinoma received intraarterial infusion of this suspension, the size of the tumor and serum level of alpha-fetoprotein was prominently decreased. This ultrasonification method was simple and convenient to prepare Dx-in-oil suspension.
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PMID:[A new method of preparation of doxorubicin-in-oil suspension using ultrasonificator attached with Cuphorn]. 217 76

Rats bearing Novikoff hepatoma ascites cells were given i.p. injections of actinomycin D, doxorubicin, or daunorubicin. Four hours after injection, tumor cells were removed from the ascites fluid and analyzed for protein B23 translocation using an immunofluorescence technique. Bright nucleolar fluorescence was observed in untreated cells. Treatment with actinomycin D (1.25 mg/kg), doxorubicin (25 mg/kg), or daunorubicin (12.5 mg/kg) produced a uniform nucleoplasmic fluorescence. This change in immunofluorescence distribution indicated that protein B23 translocated from the nucleolus to the nucleoplasm after drug treatment. These results are an extension of previous studies with HeLa cells (Yung et al., Cancer Res. 46: 922-925, 1986). Doxorubicin-resistant and -sensitive mouse leukemia cells (P388) were cultured in medium containing various doses of doxorubicin for 4 h, and the responsive levels of the cells to doxorubicin were compared. At 50 micrograms/ml doxorubicin, 86% of the doxorubicin-sensitive cells showed uniform nucleoplasmic fluorescence, and less than 2% of the cells retained nucleolar fluorescence. At this same dose, only 9% of the resistant cells showed nucleoplasmic fluorescence, and 75% of the cells retained nucleolar fluorescence. At 100 micrograms/ml, about 26% of the resistant cells showed translocation, in contrast to 100% of the sensitive cells that showed B23 translocation. About 57% of the resistant cells showed an intermediate effect, and about 17% of the resistant cells maintained bright nucleolar fluorescence at this dose. The resistant cells also showed less responsiveness to actinomycin D. These results suggest that identification of "B23 translocation" may be used to detect drug-resistant cells and to study the efficacy of certain antitumor agents.
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PMID:Nucleolar protein B23 translocation after doxorubicin treatment in murine tumor cells. 243 99

Since 1983, transcatheter oily chemoembolization (TOCE) with doxorubicin hydrochloride, iodized oil, and gelatin sponge was used in 100 patients with hepatocellular carcinoma. Doxorubicin, 40-100 mg (mean, 61.3 mg), was mixed with 5-20 mL (mean, 9.6 mL) of an iodized oil to prepare a water-in-oil emulsion that was then infused into the hepatic artery. Both progressive changes in blood concentrations of doxorubicin and its tissue concentrations in patients who underwent hepatectomy demonstrated that the drug was released slowly from the emulsion. The cumulative survival rate was 82.0% for 6 months, 53.8% for 1 year, 33.3% for 2 years, and 17.6% for 3 years. These survival rates were better than those of 104 patients who underwent embolization with gelatin sponge, then received an anticancer drug (67.4% for 6 months, 45.2% for 1 year, 16.3% for 2 years, and 3.8% for 3 years).
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PMID:Transcatheter oily chemoembolization of hepatocellular carcinoma. 253 46

Fifteen to 20 years ago, the natural history of HCC demonstrated approximately 1.5 months median survival after diagnosis with rare cases of one-year survival. Ten to 15 years ago, one shot intraarterial (IA) injection of mitomycin C (MMC) or doxorubicin (ADR) became the prevailing treatment and prolonged median survival to 3-5 months. Ten years ago, transcatheter arterial embolization was introduced and improved the survival rate dramatically. In the earlier period, TAE was performed with gelatin sponge (GS) plus ADR or MMC and showed shrinkage of HCC in the well-capsulated case. Combined use of Lipiodol (LPD) with anticancer drug and GS in later period showed further progress in antitumor response and survival. The one year survival rate obtained from our 100 cases was 53.8%, and the 2 year one was 36.5%. We speculate that the effective response of LPD plus drug to intrahepatic daughter nodules contributed to this improvement because we clarified the efflux of LPD to peripheral portal vein clinically and experimentally. Since the metastatic liver tumor originating from colon or gastric cancer is usually hypovascular and shows limited response to intra-arterial chemotherapy, a special device is needed for improvement. We introduced an S.C. implanted port for injection route and long-term intermittent IA combination therapy with ADR or MMC and degradable starch microspheres (DSM), which embolise arteries temporarily for 20-30 minutes. These new methods achieved a favorable response rate with better quality of life, and would be expected to prolong the life span of patients with metastatic liver tumor.
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PMID:[Recent progress in multidisciplinary treatment of hepatic cancer]. 254 1

When a large amount of iodized oil (LPD) is selectively administered to targeted segments of the liver, the tumor vessels and sinusoids around the tumor are filled with LPD, subsequently regurgitating excessive LPD via the hepatic arterioportal communication into the portal branches surrounding the tumor. Segmental arterioportal chemoembolization in HCC with Doxorubicin-in-oil emulsion (DOE), which we named cement therapy, was performed in 18 patients with HCC. DOE was administered selectively into one segment division of Couinaud in ten patients, two segments in seven and three segments in one. Computed tomography and ultrasonography following the cement therapy revealed an overall response rate of 39%. The one-year cumulative survival rate was 80%, and that for three-years was 33%. Three cases underwent segmental hepatectomy and these specimens revealed total necrosis of the main tumor and whole daughter nodules, followed by various degrees of hepatic parenchymal infarction. This cement therapy realizes the simultaneous chemoembolization via the artery and portal vein, and was considered an effective treatment for extra-capsular infiltration and daughter nodules of HCC nourished by the portal vein blood flow. Limited administration of DOE to the targeted segments enables transarterial oily chemoembolization (TOCE) without any serious side effects.
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PMID:[Segmental arterio-portal chemo-embolization in hepatocellular carcinoma (cement therapy)]. 255 Dec 28

In a prospective trial of 75 Chinese patients with histologically proven inoperable hepatocellular carcinoma (HCC), 25 patients were randomised to receive doxorubicin 60-75 mg m-2 intravenously once every 3 weeks, 25 to receive recombinant alpha 2 interferon (rIFN) (Roferon) 9-18 x 10(6) IU m-2 intramuscularly (i.m.) daily and 25 to receive rIFN 25-50 x 10(6) IU m-2 i.m. three times weekly. Patients were switched to the other drug if: (a) there was progressive disease after 12 weeks, (b) unacceptable toxicity developed and (c) they had received a total of 500 mg m-2 of doxorubicin. Six patients had switching over of therapy, three on doxorubicin and three on rIFN. In the remaining 69 patients on single drug therapy, the median survival rate of patients on doxorubicin and rIFN was 4.8 and 8.3 weeks respectively (P = ns.). rIFN induced tumour regression of 25-50% in 12% of patients and of over 50% in 10% of patients. When compared with doxorubicin, rIFN was associated with more tumour regression (P = 0.00199) and less progressive tumours (P = 0.00017). It caused less prolonged and less severe marrow suppression (P = 0.01217), and had significantly less fatal complications than doxorubicin (P = 0.01383). Doxorubicin caused fatal complications due to cardiotoxicity and neutropenia in 25% of patients. rIFN was associated with fatal complications due to dementia and renal failure in 3.8% of patients. In the treatment of inoperable HCC, rIFN is superior to doxorubicin in causing more tumour regression, less serious marrow suppression and less fatal complications.
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PMID:Recombinant alpha 2 interferon is superior to doxorubicin for inoperable hepatocellular carcinoma: a prospective randomised trial. 255 81

Mitoxantrone was compared with doxorubicin and aclarubicin of its in vivo antitumor activity and influence on cell cycle transition by use of rat ascitic hepatoma AH109A. Antitumor activity determined by the cell growth curve was similar in mitoxantrone and doxorubicin, but the sensitivity of AH109A to aclarubicin was lower than that to the other two drugs. Doxorubicin and mitoxantrone showed all phase arrests with 1/10 of maximally tolerated dose (MTD), and with lower concentrations a strong arrest at G2 phase was observed, thus, mitoxantrone appeared to have a similar antitumor activity on AH109A to that of doxorubicin. Aclarubicin, with 1/10 MTD, demonstrated only a transient arrest at G2 phase, cells arrested at G2 phase entering into the next phase. With below 1/10 MTD, there was no appearance on histograms, and the influence on AH109A cell cycle transition by aclarubicin was considered to be little in comparison with doxorubicin and mitoxantrone.
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PMID:[In vivo antitumor activity of mitoxantrone and the flow cytometric analysis of its influence on cell cycle transition--comparison with doxorubicin and aclarubicin on ascitic hepatoma AH109A cells]. 259 60


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