aclarubicin and Carcinoma--Hepatocellular

A female patient in whom acute nonlymphocytic leukemia (ANLL, FAB-M6) developed during treatment of hepatocellular carcinoma (HCC) is described. Two years after partial hepatectomy and subsequent chemotherapy, leukemia developed following a 2 month preleukemic stage. Chromosomal analysis revealed an abnormal karyotype, 46,XX,-5, + der(5)t(3;5)(q25;q31). The balanced translocation t(3;5) has been observed in all types of ANLL and MDS except for ANLL M3 subtype. We summarize patients with ANLL M6 and t(3;5).

Topics: Aclarubicin; Adolescent; Adult; Aged; Anemia, Refractory, with Excess of Blasts; Carcinoma, Hepatocellular; Child; Chromosomes, Human, Pair 3; Chromosomes, Human, Pair 5; Cytarabine; Daunorubicin; Doxorubicin; Female; Hepatectomy; Hepatitis B; Humans; Leukemia, Erythroblastic, Acute; Liver Neoplasms; Male; Middle Aged; Mitomycin; Neoplasm Recurrence, Local; Neoplasms, Multiple Primary; Prednisolone; Remission Induction; Translocation, Genetic

In targeted chemotherapy, Lipiodol Ultrafluid was used as a carrier of anticancer drugs; these combinations were termed oily anticancer agents. Arterial injection therapy with these oily anticancer agents was performed in 330 patients with unresectable hepatocellular carcinoma (HCC) and 110 patients with unresectable metastatic liver cancer. The alpha-fetoprotein (AFP) level decreased in 178 of 186 AFP-positive patients with HCC. Tumor size was reduced in 256 of 269 evaluable patients with HCC. The treatment seemed to prolong survival and in 193 HCC patients who were good candidates for therapy (those without Child C liver cirrhosis, without tumor occupying all four segments of the liver, or without extrahepatic spread) the 1-, 2-, and 5-year survival rates were 85, 52, and 34% respectively. In the 110 patients with metastatic liver cancer, the carcinoembryonic antigen level and tumor size were reduced. The 1-, 2-, and 5-year survival rates of these 110 patients were 61, 32, and 22% respectively.

Topics: Aclarubicin; Adolescent; Adult; Aged; Aged, 80 and over; alpha-Fetoproteins; Antineoplastic Agents; Carcinoembryonic Antigen; Carcinoma, Hepatocellular; Doxorubicin; Drug Delivery Systems; Female; Humans; Injections, Intra-Arterial; Iodized Oil; Liver Neoplasms; Male; Maleic Anhydrides; Middle Aged; Mitomycin; Polystyrenes; Survival Analysis; Survival Rate; Treatment Outcome; Zinostatin

In May 2006, a 72-year-old man with acute myelogenous leukemia (M4Eo) was admitted to our hospital. He had been receiving antiandrogen treatment for prostate cancer (after an operation in 1998) and treatment for diabetes mellitus. He received chemotherapy according to the JALSG GML200 protocol, which led to complete remission; however, in January 2007, his leukemia recurred. CAG combination chemotherapy also resulted in complete remission by May 2007. In August 2007, he developed multiple liver tumors, abdominal pain, and fever. Contrast-enhanced computed tomography revealed hypovascular tumors in both early and delayed phases. Angiography showed ring-like tumor staining and a massive tumor, similar to those seen in metastatic hepatocellular carcinomas (HCCs). He eventually died because of aggressive enlargement of liver tumors during the following month accompanied by the simultaneous recurrence of leukemia and unsuccessful embolization of the hepatic artery. Autopsy specimens showed fibrosis and considerable iron deposition in the liver, suggested secondary hemochromatosis due to transfusion. We also detected multiple moderately differentiated primary HCCs. Secondary hemochromatosis, androgen imbalance, and humoral factors from leukemic cells were believed to be the causes of the rapid onset and development of HCCs.

Topics: Aclarubicin; Aged; Androgen Antagonists; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Hepatocellular; Cytarabine; Fatal Outcome; Granulocyte Colony-Stimulating Factor; Hemochromatosis; Humans; Leukemia, Myeloid, Acute; Liver Neoplasms; Male; Neoplasms, Second Primary; Prostatic Neoplasms; Time Factors

To investigate the possibility of recombinant high-density lipoprotein (rHDL) being a carrier for delivering antitumoral drug to hepatoma cells.. Recombinant complex of HDL and aclacinomycin (rHDL-ACM) was prepared by cosonication of apoproteins from HDL (Apo HDL) and ACM as well as phosphatidylcholine. Characteristics of the rHDL-ACM were elucidated by electrophoretic mobility, including the size of particles, morphology and entrapment efficiency. Binding activity of rHDL-ACM to human hepatoma cells was determined by competition assay in the presence of excess native HDL. The cytotoxicity of rHDL-ACM was assessed by MTT method.. The density range of rHDL-ACM was 1.063-1.210 g/mL, and the same as that of native HDL. The purity of all rHDL-ACM preparations was more than 92%. Encapsulated efficiencies of rHDL-ACM were more than 90%. rHDL-ACM particles were typical sphere model of lipoproteins and heterogeneous in particle size. The average diameter was 31.26+/-5.62 nm by measure of 110 rHDL-ACM particles in the range of diameter of lipoproteins. rHDL-ACM could bind on SMMC-7721 cells, and such binding could be competed against in the presence of excess native HDL. rHDL-ACM had same binding capacity as native HDL. The cellular uptake of rHDL-ACM by SMMC-7721 hepatoma cells was significantly higher than that of free ACM at the concentration range of 0.5-10 microg/mL (P<0.01). Cytotoxicity of rHDL-ACM to SMMC-7721 cells was significantly higher than that of free ACM at concentration range of less than 5 microg/mL (P<0.01) and IC50 of rHDL-ACM was lower than IC50 of free ACM (1.68 nmol/L vs 3 nmol/L). Compared to L02 hepatocytes, a normal liver cell line, the cellular uptake of rHDL-ACM by SMMC-7721 cells was significantly higher (P<0.01) and in a dose-dependent manner at the concentration range of 0.5-10 microg/mL. Cytotoxicity of the rHDL-ACM to SMMC-7721 cells was significantly higher than that to L02 cells at concentration range of 1-7.5 microg/mL (P<0.01). IC50 for SMMC-7721 cells (1.68 nmol/L) was lower than that for L02 cells (5.68 nmol/L), showing a preferential cytotoxicity of rHDL-ACM for SMMC-7721 cells.. rHDL-ACM complex keeps the basic physical and biological binding properties of native HDL and shows a preferential cytotoxicity for SMMC-7721 hepatoma to normal L02 hepatocytes. HDL is a potential carrier for delivering lipophilic antitumoral drug to hepatoma cells.

Topics: Aclarubicin; Antibiotics, Antineoplastic; Carcinoma, Hepatocellular; Cell Line, Tumor; Drug Carriers; Hepatocytes; Humans; Lipoproteins, HDL; Liver Neoplasms

Advanced hepatocellular carcinoma (HCC) with extensive tumour growth through the hepatic vein still has an extremely poor prognosis, even after cancer chemotherapy and/or transarterial embolization. Although aggressive surgical treatments using extracorporeal circulation and liver transplantation have been performed by some authors, the reported results were still unsatisfactory. In this study, we report the favourable result of hepatic artery chemoembolization and subsequent surgical resection in three patients with advanced HCC with extensive tumour thrombus through the hepatic vein.. Three irresectable patients with HCC with extensive tumour thrombus through the hepatic vein underwent hepatic artery chemoembolization with aclarubicin, mitomycin C, lipiodol and/or Gelfoam. After the reduction of tumour extent with hepatic artery chemoembolization, two of the three patients underwent surgical resection. These two patients are still alive at 59 and 21 postoperative months, respectively. In the other case, the extent of the tumour and functional reserve of the liver prevented us from performing surgical resection, but the patient is doing well 62 months after the initial treatment.. Hepatic artery chemoembolization with aclarubicin, mitomycin C, lipiodol and/or Gelfoam might be an effective treatment for irresectable advanced HCC with extensive tumour thrombus into the inferior vena cava or the right atrium through the hepatic vein. Radical surgical resection might be applicable for selected patients without high surgical risk after reducing tumour extent by hepatic artery chemoembolization.

Topics: Aclarubicin; Aged; Antibiotics, Antineoplastic; Budd-Chiari Syndrome; Carcinoma, Hepatocellular; Chemoembolization, Therapeutic; Gelatin Sponge, Absorbable; Hepatic Artery; Humans; Iodized Oil; Liver Neoplasms; Male; Middle Aged; Mitomycin; Neoplastic Cells, Circulating; Radiography

Topics: Aclarubicin; Antibiotics, Antineoplastic; ATP Binding Cassette Transporter, Subfamily B, Member 1; Carcinoma, Hepatocellular; Cyclosporins; Daunorubicin; Dose-Response Relationship, Drug; Doxorubicin; Drug Resistance, Multiple; Epirubicin; Humans; Liver Neoplasms; Tumor Cells, Cultured

Drug resistance is a major obstacle to successful chemotherapy of primary liver cancer, which is associated with high expression of the multidrug resistance (MDR) gene product P-glycoprotein (Pgp), a multidrug efflux transporter. The most effective single agents in treatment of primary liver carcinoma belong to the anthracycline family, yet several anthracyclines are known to be substrates for Pgp. In the present study, we compared four anthracyclines with respect to cell growth inhibition, intracellular accumulation and cellular efflux using the HB8065/R human hepatoma cell line which is rich in Pgp, and the Pgp-poor parental line HB8065/S. The anthracyclines were also administered in conjunction with the Pgp-modifying agents verapamil and SDZ PSC 833 to assess modulation of resistance. The HB8065/R cells were sensitive to aclarubicin (ACL) and highly resistant to epirubicin (EPI), doxorubicin (DOX) and daunorubicin (DNR). SDZ PSC 833 enhanced accumulation, decreased efflux and increased cytotoxicity of EPI, DOX and DNR in the HB8065/R cells, but none of these effects was seen with ACL. In conclusion, ACL is apparently not transported by Pgp and retains its activity in a multidrug-resistant human hepatoma cell line; such properties can be exploited for clinical purposes.

Topics: Aclarubicin; Antibiotics, Antineoplastic; ATP Binding Cassette Transporter, Subfamily B, Member 1; Carcinoma, Hepatocellular; Cell Division; Cell Membrane; Daunorubicin; Doxorubicin; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Drug Screening Assays, Antitumor; Epirubicin; Humans; Liver Neoplasms; Microscopy, Confocal; Tumor Cells, Cultured

In an attempt to investigate the interaction between the changes of cytokines and acute phase reactants after transcatheter arterial chemoembolization therapy (TACE), the levels of interleukin 6 (IL-6), interleukin 8 (IL-8), C-reactive protein (CRP) and pancreatic secretory trypsin inhibitor (PSTI) in the blood of patients with unresectable hepatocellular carcinoma (HCC) were measured. Before the therapy, serum IL-6 and plasma IL-8 levels were detectable in 77.8% and 28.5%, respectively, of patients with HCC. Levels of serum IL-6 and plasma IL-8 increased after TACE and reached a peak on day 3 in all patients (18/18) and in 87.5% of patients (12/14), respectively. Both blood levels of IL-6 and IL-8 reached a peak earlier than those of CRP and PSTI did after the therapy. When the maximal values of IL-6 were compared with those of CRP and PSTI, there were significant positive correlations (r = 0.63, P < 0.01 and r = 0.81, P < 0.01, respectively). Similarly, comparisons of the maximal values of IL-8 with those of CRP and PSTI gave a significant correlation (r = 0.68, P < 0.01 and r = 0.67, P < 0.05, respectively). However, no significant correlation was found between the elevation of IL-6 and IL-8.

Topics: Aclarubicin; Acute-Phase Reaction; C-Reactive Protein; Carcinoma, Hepatocellular; Chemoembolization, Therapeutic; Cisplatin; Cytokines; Humans; Interleukin-6; Interleukin-8; Liver Neoplasms; Trypsin Inhibitor, Kazal Pancreatic

Sixty-six consecutive patients with unresectable hepatocellular carcinoma (HCC) were treated with transcatheter arterial chemoembolization (TACE) using aclarubicin microspheres (ACRms) in combination with cisplatin suspended in iodized oil (Lipiodol, Laboratoire Guerbert, Paris, France) (CSL). The stages of the disease were as follows: Stage I (n = 1), Stage II (n = 10), Stage III (n = 26), and Stage IV (n = 29). The effectiveness of TACE was assessed by comparing ACRms with CSL with ACRms without CSL. Of 66 patients treated with ACRms and CSL, 62 (93.9%) could be examined for response. According to response criteria, there were 31 (50.0%) partial responses and 17 (27.4%) minor responses. In 13 cases (21.0%) there was no change and in 1 case (1.6%) there was progressive disease. The cumulative survival rate was 80.7% at 1 year, 64.2% at 2 years, and 50.6% at 3 years. The rates were significantly higher than those of the group treated with ACRms. Eleven patients in the ACRms and CSL group experienced clinical complications: cholecystitis (4.5%), pancreatitis (3.0%), liver abscess (3.0%), hepatic failure (3.0%), gastrointestinal bleeding (1.5%), and renal failure (1.5%). No lethal side effects related to the therapy were observed. TACE using ACRms in combination with CSL prolongs the survival of patients with unresectable HCC.

Topics: Aclarubicin; Adult; Aged; Aged, 80 and over; Carcinoma, Hepatocellular; Chemoembolization, Therapeutic; Cisplatin; Female; Humans; Iodized Oil; Liver Neoplasms; Male; Microspheres; Middle Aged; Neoplasm Staging; Survival Analysis; Treatment Outcome

Transcatheter arterial chemoembolization therapy using polylactic acid microspheres containing aclarubicin hydrochloride (ACR) was performed in 62 patients with primary hepatocellular carcinoma. These microspheres were about 200 microns in diameter and contained 10% (w/w) aclarubicin. A single dose of polylactic acid microspheres containing ACR (50-100 mg of ACR) was administered 1 to 8 times with a mean of 2.2 doses (a total of 160 treatments) in 62 patients. Antitumor effects were observed from the decrease in serum alpha-fetoprotein levels (82.1% of the patients) and in two dimensional size of tumor on computed tomography (93.6%). The cumulative survival rate was 54.3% at 1 year, 24.6% at 2 years, and 19.2% at 3 years, respectively, among 59 patients with unresectable tumors. In 3 resected liver specimens, there was a significant accumulation of ACR in the tumor, and severe necroses of the tumors were observed histologically. Systemic toxicity was mild and all patients tolerated this treatment. These results suggest that transcatheter arterial chemoembolization with the use of polylactic acid microspheres containing ACR is a useful tumor-targeting chemotherapy and is effective in the treatment of hepatocellular carcinoma.

Topics: Aclarubicin; Adult; Aged; alpha-Fetoproteins; Animals; Carcinoma, Hepatocellular; Dogs; Embolization, Therapeutic; Female; Humans; Infusions, Intra-Arterial; Lactates; Lactic Acid; Liver Neoplasms; Male; Microspheres; Middle Aged; Polyesters; Polymers

A new immunotherapy for hepatocellular carcinoma (HCC) using Freund's adjuvant and recombinant interleukin-2 (IL-2) combined with conventional transarterial chemoembolization therapy was performed. In 16 patients with HCC and one patient with metastatic liver cancer receiving this therapy, decrease and suppression of reelevation of alpha-fetoprotein after therapy was observed. Disappearance of tumor thrombi of HCC in the main portal vein was observed in a patient, and decrease of carcinoembryonic antigen was also observed in a patient with metastatic liver cancer. The present therapy using Freund's adjuvant and IL-2 is likely to open a new avenue for the treatment of patients with advanced liver cancer.

Topics: Aclarubicin; Adult; Aged; alpha-Fetoproteins; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Hepatocellular; Combined Modality Therapy; Embolization, Therapeutic; Female; Freund's Adjuvant; Humans; Interleukin-2; Iodized Oil; Liver Neoplasms; Male; Middle Aged; Mitomycin; Mitomycins; Recombinant Proteins

Chemosensitivity to six different types of antitumor drugs was assayed using the succinate dehydrogenase inhibition (SDI) test, with regard to effects of 29 tissues from primary hepatocellular carcinomas (PHC) and 12 metastatic liver cancers. Succinate dehydrogenase activity in the PHC was significantly decreased by adriamycin (ADM), mitomycin C (MMC), aclacinomycin A (ACR) (P less than 0.01), and 5-fluorouracil (5-FU), cisplatin (DDP) and carboquone (CQ) (P less than 0.05), as compared to findings in tissues from the metastatic liver tumors. In PHC, chemosensitivity to antitumor drugs in the SDI test was positive in 58.6% of tissues exposed to ADM, 60.7% with MMC, 11.1% with 5-FU, 65.4% with DDP, 65.5% with ACR and 64.3% with CQ. On the contrary, the positive rates seen in metastatic liver tissues were 18.2% in DDP and 8.3% in CQ, and there was no positive chemosensitivity in tissues exposed to ADM, MMC, 5-FU and ACR. Therefore, PHC will show a better response than metastatic liver cancers to antitumor drugs. Our observations show that the selection of sensitive drugs is most important to improve the response rate and the survival time of patients. The SDI test proves useful for planning clinical management.

Topics: Aclarubicin; Antineoplastic Agents; Carbazilquinone; Carcinoma, Hepatocellular; Cisplatin; Doxorubicin; Drug Screening Assays, Antitumor; Female; Fluorouracil; Humans; Liver Neoplasms; Male; Mitomycin; Mitomycins; Succinate Dehydrogenase

The lipid lymphographic agent, Lipiodol ultrafluid has been found to remain selectively in hepatocellular carcinoma. Using this characteristic nature of Lipiodol, a new targeting anticancer chemotherapy was devised. In order to achieve targeting anticancer chemotherapy and useful anticancer effects, anticancer drugs must be dissolved or suspended in Lipiodol and diffuse out from the Lipiodol gradually. Oily anticancer agents such as SMANCS dissolved in Lipiodol (SMANCS/Lipiodol), Mitomycin C in Lipiodol (MMC/Lipiodol), Aclarubicin in Lipiodol (ACR/Lipiodol) and a mixture of these were administered by catheterizing the celiac or hepatic artery under X-ray monitoring in 216 patients with hepatocellular carcinoma. Remarkable anticancer effects of this targeting chemotherapy were achieved, the serum AFP level and tumor size both showing a decrease in 91% of cases. The survival period of patients with unresectable hepatoma treated with the present protocol was definitely longer than the comparison group.

Topics: Aclarubicin; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Hepatocellular; Embolization, Therapeutic; Humans; Infusions, Intra-Arterial; Iodized Oil; Liver Neoplasms; Maleic Anhydrides; Mitomycin; Mitomycins; Naphthacenes; Polystyrenes; Zinostatin

Transcatheter hepatic arterial embolization therapy (TAE) is an established method for the treatment of hepatocellular carcinoma (HCC). We have developed a new embolus consisting of microspheres with a mean diameter of about 200 microns which are composed of biodegradable polymolecular polylactic and the anti-cancer agent, aclarubicin -HCl, in a ratio of 12% w/w. These microspheres were applied to 28 patients with inoperable HCC using the following method microspheres containing 50 mg of aclarubicin-HCl were injected through a catheter placed in the hepatic artery or one of its branches, 2 or 3 times at intervals of 2 to 4 weeks. The effectiveness was confirmed by decreased levels of serum AFP and regression of the tumor size, and the accumulated survival rate for 6 months was 83.3%.

Topics: Aclarubicin; Antibiotics, Antineoplastic; Carcinoma, Hepatocellular; Catheterization; Embolization, Therapeutic; Hepatic Artery; Humans; Lactates; Lactic Acid; Liver Neoplasms; Microspheres; Naphthacenes; Polyesters; Polymers