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At least 253 records · Page 14Linked to original sources
PubMed2004

Induction of apoptosis by the proteasome inhibitor MG132 in human HCC cells: Possible correlation with specific caspase-dependent cleavage of beta-catenin and inhibition of beta-catenin-mediated transactivation.

Proteasome inhibitors, like MG132, can exert cell growth inhibitory and apoptotic effects in different tumor types. The apoptotic mechanism of these compounds involves the activation of the effector caspases. beta-catenin, also an oncogene, represents one of the substrates of these proteases, but the consequences of its cleavage are poorly understood. We investigated its function during apoptosis induced by MG132 in three hepatocellular carcinoma (HCC) cell lines, endowed (HepG2 and HuH-6) or not (HA22T/VGH) with activating mutations of beta-catenin. Induction of apoptosis was associated with cell growth inhibition, accumulation of the cells at the G(2)/M phases of the cell cycle, as well as with fragmentation of beta-catenin (but not of alpha- or gamma-catenin) in all the cell lines. The cleavage of beta-catenin was inhibited by the caspase inhibitors Z-VAD-fmk and Z-DEVD-fmk. Fragmented beta-catenin was found in the nuclei of the treated cells. Analyses through the reporter plasmid pTOPflash showed that MG132 significantly reduces Tcf transcriptional activity in the cells. This was associated with a decrease in the mRNA expression of survivin and c-myc, which are target genes of the APC/beta-catenin/Tcf signaling. Nevertheless, Z-VAD-fmk or Z-DEVD-fmk did not reverse the MG132 effects on Tcf transcriptional activity, suggesting that the compound may affect this activity also by other mechanisms. Overall, the present study supports the therapeutic potential of the proteasome inhibitors in HCC.

Amino Acid Chloromethyl Ketones↗
PubMed2004

[A case report of the local treatment against hepatocellular carcinoma (HCC) in consideration of the prospective living donor liver transplantation (LDLT)].

Various local cancer treatments became possible in the cure of hepatocellular carcinoma. Percutaneous ethanol injection (PEIT), a local ablation therapy such as microwave and radiofrequency were added to the transcatheter arterial chemoembolization (TACE) and hepatectomy. However, it is also a well-known fact to repeat hepatic carcinogenesis by the conditions of a background liver whereas to originate in the viral hepatitis. In this point of view, liver transplantation is one of the ultimate treatments to get rid of the carcinogenic factor. A 54-year-old man patient diagnosed as HCC strongly hoped for the prospective liver transplantation surgery from the beginning. Therefore, we had to treat a liver cancer in consideration of the prospective liver transplantation. A local ablation therapy and TACE treatment were carried out with being careful not to have an influence to the transplantation surgery. Because recurrence was repeated, a patient chose a transplantation medical treatment after one year and nine months. We reported the process of local treatments against HCC in consideration of the prospective liver transplantations.

Carcinoma, Hepatocellular↗
PubMed2005

[A clinical study of endoscopic local coagulation therapy for hepatocellular carcinoma (HCC)].

Eighteen subjects with cases of HCC who underwent endoscopic local coagulation therapy at Hiroshima City Hospital between 1998 and 2004 were studied and compared with 6 cases of HCC patients who underwent laparoscopic partial hepatectomy during the same period. The subjects composed of 10 cases of laparoscopic microwave coagulation therapy (L-MCT), 5 cases of laparoscopic radio frequency ablation therapy (L-RFA), and 3 cases of thoracoscopic microwave coagulation therapy (T-MCT). The operation time was 114 minutes for L-MCT and 92 minutes for L-RFA, both of which were significantly shorter than 208 minutes for resection cases. No complications were developed in any of the cases and the postoperative hospitalization period of the cases was 13.1 days, 8.2 days, and 13.0 days, respectively. Although each case of local recurrence was observed both in L-MCT and L-RFA groups, one case displayed observation difficulty from the liver surface and the other required a daughter nodule. The three-year survival rate was 71.4%, while the five-year survival rate was 53.6%. Endoscopic local coagulation therapy is not too invasive and useful for hepatocellular carcinoma in which percutaneous RFA is difficult. However, it is well indicated when the scope is evident with observation being feasible from the liver surface.

Carcinoma, Hepatocellular↗
PubMed2006

[Natural history of Japanese patients with non-alcoholic fatty liver disease (NAFLD), especially non-alcoholic steatohepatitis (NASH) patients with hepatocellular carcinoma (HCC)].

Our current knowledge of the natural history of NAFLD can be summarized as follows: 1) simple steatosis can progress to steatohepatitis, fibrosis, cirrhosis, and even liver-related death but progression occurs in less than 5% of patients, 2) patients with NASH can progress to cirrhosis, 3) once cirrhosis develops in patients with NAFLD the prognosis appears to be poor with several studies reporting that some patients develop HCC and up to a third of patients develop liver-related morbidity or mortality, 4) older age and advanced fibrosis are risk factors for HCC in NASH. Changes in lifestyle have resulted in a dramatic increase in the prevalence of NAFLD. It is extremely important that we diagnose NASH definitely and perform appropriate treatment.

Asian People↗
PubMed2006

[S-1 treatment against advanced HCC].

We have reported a remarkably high anti-tumor efficacy using intra arterial 5-FU infusion chemotherapy combined with subcutaneous interferon-alpha injection to treat advanced hepatocellular carcinoma (HCC) with portal vein thrombus. However, we have been confirming distant metastases along with a prognosis extension as hepatic lesions could possibly be controlled to a certain extent. Even though there has been no effective chemotherapy against hepatocellular carcinoma with distant metastases, we performed S-1 and interferon-alpha combination chemotherapy for the cases where good results were exhibited from interferon-alpha combined with arterial 5-FU infusion. As a result, we confirmed CR in the anti-tumor effect against distant metastases with no severe adverse effects. It was suggested that a combination therapy of S-1 and interferon-alpha may be one of the most effective treatment modalities against advanced HCC with distant metastases.

Administration, Oral↗
PubMedDate not supplied

Hemoperitoneum as a first manifestation of HCC with bleeding from ruptured aberrant vessel: a case report.

A young man presented with a history of abdominal pain and distension for 4 days. Diagnosis of spontaneous hemoperitoneum was made after clinical examination, abdominal USG and a diagnostic peritoneal tap. Emergency laparotomy revealed massive hemoperitoneum with extensive bilobar hepato-cellular carcinoma (HCC). A ruptured aberrant vessel communicating between the intercostal vessel and HCC in the liver had caused massive hemoperitoneum.

Adult↗
PubMedDate not supplied

Evaluation of the therapeutic effect using MD-CT immediately after RFA for HCC.

BACKGROUND/AIMS: Radiofrequency ablation (RFA) is an effective modality for treatment of hepatocellular carcinoma (HCC), because it can induce large coagulation necrosis in a few sessions. The aim of this study is to evaluate whether we can assess the therapeutic effect of RFA immediately after RFA. METHODOLOGY: Twenty-one patients (25 nodules) with HCC undergoing RFA treatment were enrolled in this study. Fourteen patients were treated with combination therapy of lipiodol chemoembolization and RFA, while 7 patients were treated with RFA alone. Dynamic computed tomography (CT) using multidetector row helical CT (MD-CT) was performed before, immediately after and 1 week after RFA. Simultaneously, multiplanar reconstruction (MPR) images were also obtained for comparison. RESULTS: With or without chemoembolization, the size of coagulated necrosis was almost the same between the time immediately after and 1 week after RFA. The therapeutic effect was able to be evaluated by dynamic CT scans immediately after RFA in all patients. Moreover, MPR images facilitate the detailed evaluation of the therapeutic effect. CONCLUSIONS: Examination of dynamic CT using MD-CT immediately after RFA is useful to evaluate the therapeutic effect and may enable a shorter hospital stay.

Aged↗
PubMed1989

Validity of MR imaging for monitoring effects of percutaneous ethanol injection for HCC.

Magnetic resonance (MR) images of 44 hepato-cellular carcinoma (HCC) patients who had undergone percutaneous ethanol injection therapy (PEIT) were analyzed during and after the treatment. Using a long TE/TR spin-echo technique, the initial high intensity of the tumor decreased during treatment in all patients. Decrease in tumor intensity corresponded well with decrease of serum alpha-fetoprotein level and histopathological changes of the necrosis. During the long-term follow-up of three patients, the reappearance of a highly intense area was readily detected by MR imaging, and hence the recurrence of the tumor, as determined clinically or histopathologically, was confirmed. The long TE/TR spin-echo technique proves most helpful in monitoring the effectiveness of PEIT for HCC, as well as for its recurrence.

Carcinoma, Hepatocellular↗
PubMed1986

[Randomized clinical trial of cis-platinum diamminedichloride (PDD) in the treatment of hepatocellular carcinoma (HCC)].

From Oct. 1982 to Apr. 1985, 82 patients with HCC proven by pathology were treated in our hospital. 43 treated by hepatic arterial perfusion, were randomized into PDD group: PDD 10 mg per day X 10, every 3 weeks; control group: fluorouracil (5-Fu) 250 mg per day X 4, every week and thio-tepa (TSPA) 10 mg, twice a week. The other 39 treated by intravenous chemotherapy, were also randomized into PDD group: PDD 20 mg per day X 5, every 3 weeks; control group: 5-Fu 500 mg and TSPA 10 mg, twice a week. The objective response rates were 31.8% (7/22) in PDD group and 23.8% (5/21) in control group by hepatic arterial perfusion, and 20.0% (4/20) in the former and 0% (0/19) in the latter who were treated intravenously. The median survivals were 8 months for all the patients receiving hepatic arterial perfusion, and 6 and 5 months for the intravenous PDD and its control group, respectively. The side effects and kidney toxicity of PDD were tolerable to the patients. It is observed that PDD is better than 5-Fu and TSPA in the treatment of HCC.

Carcinoma, Hepatocellular↗
PubMed1994

[Analysis of nuclear DNA heterogeneity of the hepatocellular carcinoma (HCC)].

To evaluate the objective proliferative activity in HCC nuclear DNA contents were measured by means of microspectrophotometry and at the same time the immunohistochemical technique using anti-PCNA antibody was employed. Surgically resected 26 HCCs were analyzed in terms of cell proliferative activity and regional heterogeneity. The analysis was performed by immunohistochemical demonstration of PCNA and pathologic histochemical study in formalin-fixed, paraffin-embedded specimens and cytophotometric measurements of nuclear DNA contents in fresh specimens. The results were as follows. 1) Nine HCCs showed regional ploidy heterogeneity. 2) PCNA labeling index and histological grade of the marginal area was much higher than that of the central area. From these results, we concluded that in the process of the HCC progression proliferative activity was decreased in the central area and was not decreased in the marginal area.

Carcinoma, Hepatocellular↗
PubMed1996

[The effects of preoperative transcatheter arterial chemoembolization (TAE) for the recurrence of hepatocellular carcinoma (HCC) from the viewpoint of consecutive tumor necrosis effect].

From 1990 to 1994, seventy-seven patients with HCC below 10 cm in tumor diameter underwent hepatic resections after TAE. They were divided into two groups: group C, complete necrosis (over 90% histologically at the maximum cutting surface of the specimen): group I, incomplete necrosis (under 90%). There were no significant differences in clinical background of patients, histopathological features and total disease-free survival rate (DFR) between the two groups. Nevertheless, DFR of patients in group C was significantly better than that of patients in group I, limiting the patients for curative resection. It was suggested that the recurrence of HCC after resection might be inhibited by curative operation following preoperative TAE with complete necrosis of tumor.

Adult↗
PubMedDate not supplied

Postoperative adjuvant chemotherapy after radical hepatic resection for hepatocellular carcinoma (HCC).

BACKGROUND/AIMS: This prospective randomized study was aimed to clarify the efficacy of epirubicin after radical hepatic resection for hepatcellular carcinoma (HCC). MATERIALS AND METHODS: One hundred and one patients entered the present study and were randomly allocated to Group A in which UFT (300 mg/day) was given from 5th postoperative week for one year, or Group B in which a bolus injection of epirubicin (40 mg/m2) was given arterially, in addition to the same UFT administration, on day 28. Groups A and B included 40 and 48 eligible cases, respectively. RESULTS: No obvious intergroup differences were observed including prescribed dose of UFT. The 1-, 3- and 5-year survival rates (Groups A vs B) were 82 vs 90%, 50 vs 49% and 35 vs 30% (p = 0.2162). Excluding 4 operative deaths, the recurrence-free survival rates were 65 vs 70%, 32 vs 37% and 14 vs 17% (p = 0.3843). Initial recurrence sites were also similar. CONCLUSIONS: A bolus arterial injection of epirubicin does not change the long term results after radical hepatic resection for HCC.

Aged↗
PubMed1997

[Early HCC and adenomatous hyperplasia: evaluation of arterial and portal blood flow with CTA, CTAP, and pathologic correlation].

In order to analyze the hemodynamic properties of early hepatocellular carcinoma (HCC) and adenomatous hyperplasia (AH), three lesions (two HCCs, one AH) depicted as hypoattenuating at CTA and iso attenuating at CTAP were correlated with the histopathological findings. The number of normal hepatic arteries in the tumor was lower than in the liver. Degeneration and narrowing of the lumens were also seen microscopically. All tumors showed the replacing growth pattern and had similar numbers of the portal tracts in the tumor to the liver. The decreased number of intratumoral normal arteries is suspected to be a characteristic finding of the early stage of HCC.

Adenoma↗
PubMed2001

Proteome analysis of a human heptocellular carcinoma cell line, HCC-M: an update.

Recently, we reported the proteome analysis of a human hepatocellular carcinoma cell line, HCC-M (Electrophoresis 2000, 21, 1787-1813), using two-dimensional gel electrophoresis (2-DE) and matrix assisted laser desorption/ionization-time of flight-mass spectrometry (MALDI-TOF-MS). From a total of 408 unique spots excised from the 2-DE gel, 301 spots yielded good MALDI spectra. Out of these, 272 spots had matches returned from the database search leading to the identification of these proteins. Here, we report the results on the identification of the remaining 29 spots using nanoelectrospray ionization-tandem mass spectrometry (nESI-MS/MS). First, "peptide tag sequencing" was performed to obtain partial amino acid sequences of the peptides to search the SWISS-PROTand NCBI nonredundant protein databases. Spots that were still not able to find any matches from the databases were subjected to de novo peptide sequencing. The tryptic peptide sequences were used to search for homologues in the protein and nucleotide databases with the NCBI Basic Local Alignment Search Tool (BLAST), which was essential for the characterization of novel or post-translationally modified proteins. Using this approach, all the 29 spots were unambiguously identified. Among them, phosphotyrosyl phosphatase activator (PTPA), RNA-binding protein regulatory subunit, replication protein A 32 kDa subunit (RP-A) and N-acetylneuraminic acid phosphate synthase were reported to be cancer-related proteins.

Carcinoma, Hepatocellular↗
PubMed2004

Selection of candidates with HCC for transplantation in the MELD era.

1. Liver transplantation is the main option for patients with early HCC who are not optimal candidates for surgical resection. 2. Shortage of donors is its main limitation, as waiting for a liver allows the tumor to progress and induce exclusion from the waiting list and death. 3. The absence of randomized controlled trials hinders the establishment of the most effective therapy to prevent tumor progression while waiting. 4. Live donation may be a cost-effective approach if optimal results are expected and the mortality risk for the donor is kept below .3%. 5. Priority policies have to be developed and refined to provide a fair and effective distribution of cadaveric organs.

Carcinoma, Hepatocellular↗
PubMed2001

Expression of the Hoxa-13 gene correlates to hepatitis B and C virus associated HCC.

To study the Hoxa-13 gene in the liver, we examined its expression by RT-PCR in various liver cell lines, rat livers under different conditions, and human primary hepatocellular carcinomas (HCCs). The gene was found to be expressed in cell lines originating from liver stem-like cells, but not in cell lines originating from hepatocytes and bile duct epithelia. Expression was induced in rat livers after treatment with d-galactosamine, which is known to induce oval cell proliferation, but not after a two-thirds partial hepatectomy (2/3 PH) where induction of oval cell proliferation is thought not to occur. Expression of the gene correlated with human HCC samples associated with Hepatitis B or C virus infection in this small series. These results suggest that the Hoxa-13 gene may provide a potentially useful tool for elucidation of mechanisms involved in lineage-specific differentiation and carcinogenesis of liver stem cells.

Animals↗
PubMed2000

Molecular bases for the development of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC).

Hepatocellular carcinoma (HCC) is the most common histological form of primary liver cancer; the tumor cells having retained features of hepatocytic differentiation. It is important to emphasize the heterogeneity of the histological background on which the tumor develops. Most HCCs complicate the evolution of an active or inactive cirrhosis. However, some tumors occur on livers with minimal histological changes; the prevalence of such cases varies from one geographical region to the other; being much higher in the southern half of Africa (around 40% of HCCs) than in Asia, America and Europe, where at least 90% of HCCs are associated in the cirrhosis. This heterogeneity is probably a reflection of different environmental and genetic factors. A large number of epidemiological and molecular studies have indeed clearly demonstrated the prime importance of environmental factors to the development of primary liver cancers in humans. Chronic hepatitis B (HBV) and C (HCV) infections are major risk factors. This review will mainly analyse the impact of chronic HBV infection but it is important to emphasize the potential synergistic effects between HBV and HCV, as well as between viral infections and other environmental factors, such as alcohol, chemical carcinogens (see review by Dr Wogan) and other, still poorly defined, hormonal factors which may account for the higher incidence of the tumor in man. Finally the review by Dr Buendia highlights the emerging issue of liver-cancer genetics.

Apoptosis↗
PubMed1994

Automated sequencing of amino acid spin systems in proteins using multidimensional HCC(CO)NH-TOCSY spectroscopy and constraint propagation methods from artificial intelligence.

We have developed an automated approach for determining the sequential order of amino acid spin systems in small proteins. A key step in this procedure is the analysis of multidimensional HCC(CO)NH-TOCSY spectra that provide connections from the aliphatic resonances of residue i to the amide resonances of residue i + 1. These data, combined with information about the amino acid spin systems, provide sufficient constraints to assign most proton and nitrogen resonances of small proteins. Constraint propagation methods progressively narrow the set of possible assignments of amino acid spin systems to sequence-specific positions in the process of NMR data analysis. The constraint satisfaction paradigm provides a framework in which the necessary constraint-based reasoning can be expressed, while an object-oriented representation structures and facilitates the extensive list processing and indexing involved in matching. A prototype expert system, AUTOASSIGN, provides correct and nearly complete resonance assignments with one real and 31 simulated 3D NMR data sets for a 72-amino acid domain, derived from the Protein A of Staphylococcus aureus, and with 31 simulated NMR data sets for the 50-amino acid human type-alpha transforming growth factor.

Amino Acid Sequence↗