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)

HepG2 cells, a human hepatoma cell line, stably expressing NADPH-cytochrome P450 reductase (OR) and/or cytochrome P450 2D6 wild-type (CYP2D6-WT) or its variants (Pro34Ser, Gly42Arg, Arg296Cys and Ser486Thr) were established in the present study. The cultivation of HepG2 cells expressing CYP2D6-WT in the culture medium containing dimethyl sulfoxide (DMSO, 0.1% of final concentration) markedly increased the bufuralol (BF) 1''-hydroxylase activity compared with that of control cells when cultivated without DMSO. A similar effect was also observed in HepG2 cells stably expressing CYP2D6 and OR. The addition of hemin in place of DMSO to the culture medium resulted in no increase in the enzyme activity. Western blot analysis revealed that the levels of CYP2D6 protein were similar between DMSO-treated and non-treated HepG2 cells regardless of OR expression. Spectrophotometric analysis of reduced carbon monoxide-difference spectra of HepG2 cells expressing CYP2D6-WT and/or OR demonstrated that the addition of DMSO increased the peak height of functional CYP2D6 at 450 nm. These results suggest that the increase in CYP2D6 activity is attributable to the radical-scavenging effect of DMSO. The HepG2 cell lines stably expressing OR and CYP2D6 or its variants in combination with DMSO treatment may be useful for screening the cytotoxicity of chemical compounds which undergo oxidation by CYP2D6.
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PMID:The effect of dimethyl sulfoxide on the function of cytochrome P450 2D6 in HepG2 cells upon the co-expression with NADPH-cytochrome P450 reductase. 1621 21

The method for early detection of hepatocellular carcinoma (HCC) has been well-established in Japan by means of regularly screening patients at risk for developing HCC by using imaging and tumor markers. An important issue is the accurate characterization of nodular lesions found in cirrhotic livers. This problem has been addressed by development of imaging modalities such as ultrasonography angiography with intra-arterial injection of CO2, computed tomography during hepatic arteriography, and computed tomography during arterial portography. It is most important to differentiate the typical hemodynamic patterns of low-grade dysplastic nodule including arterial hypovascularity with preserved portal perfusion from those of HCC characterized by arterial hypervascularity with decreased portal perfusion. At present, these findings are easily obtained by contrast-enhanced phase-invasion harmonic imaging, which is a noninvasive ultrasound technology. Radiofrequency ablation is an efficient technique to curatively treat early-stage HCC. The 5-year survival rate of RFA at our institution is 76%. Although local recurrence rate after curative RFA is as low as 6.2%, the intrahepatic distant metastasis is as high as 85% at 5 years. The prevention of intrahepatic distant recurrence by maintenance interferon therapy is thus very important. The 5-year survival rate and first, second, and third recurrence rates after curative RFA in patients who had maintenance interferon therapy were much better than those in patients who did not receive interferon therapy after curative RFA. In conclusion, recent progress in screening, diagnostic, and therapeutic strategy for early-stage HCC has improved the prognosis of patients with HCC. Furthermore, advances of prognostic staging system, such as Japan Integrated Staging score, facilitate the management of HCC.
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PMID:Early detection and curative treatment of early-stage hepatocellular carcinoma. 1623 64

Calculations at the CCSD(T)/aug-cc-pVDZ//B3LYP/6-31G(d) level of theory indicate that the anions -CCCO2H and HCCCO2(-) are stable species in their singlet states. Upon collision-induced, vertical one-electron oxidation under neutralisation-reionisation (-NR+) conditions, they produce the neutral molecules CCCO2H and HCCCO2, respectively. Some of the CCCO2H neutrals should be stable for the duration of the neutralisation-reionisation experiment (10(-6) s), while others will dissociate to CCCO and OH (requires 125 kJ mol(-1)). In contrast, neutral HCCCO2 is expected to be much less stable, and dissociate to HCC and CO2 (37 kJ mol(-1)). Neither CCCO2H nor HCCCO2 is expected to interconvert, or to rearrange to other isomers. The anions -CCCO2H and HCCCO2(-) have been formed in the ion source of the mass spectrometer by the reactions between (CH3)3Si-C[triple bond]C-CO2H and F- and HC[triple bond]C-CO2Si(CH3)3 and F-, respectively. The -NR+ spectrum of -CCCO2H shows a recovery signal and also indicates that the lowest energy dissociation pathway of neutral CCCO2H corresponds to the loss of OH. The -NR+ spectrum of HCCCO2 displays little or no recovery signal, and the spectrum is dominated by the [CO2]+ ion. The experimental observations are in agreement with the predictions of the extensive theoretical studies.
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PMID:The formation of neutral CCCO2H and HCCCO2 molecules from anionic precursors in the gas phase: a joint experimental and theoretical study. 1630 48

We reported a 60-year-old male patient with hepatocellular carcinoma (HCC) of 5cm in diameter with advanced tumor thrombosis in the left main trunk of portal vein and bile duct. He was treated with multimodal treatments resulting in a long-term survival of more than 4 years. At first, he was treated with transcatheter arterial chemoembolization (TACE) in April 1999, but the therapeutic effect was insufficient. Therefore, we performed an extended left hepatic lobectomy in July. Since six HCCs appeared in a posterior segment in January 2000, we achieved microwave coagulation therapy under laparotomy. Because of diffuse relapse of HCCs in the same segment of the liver, we performed hepatic arterial chemotherapy (HAC) using low-dose CDDP and 5-FU. As a result, complete disappearance of the tumors was observed. A new lesion appeared in S7 in January 2001. We performed TACE, but relapsed in June, so we selected percutaneous radio-frequency ablation under CO2 angiography. Since a recurrent tumor was detected at the same therapeutic site with invasion to the diaphragm in September 2002, we performed a partial liver resection with synchronous excision of the diaphragm. We continued TACE and systemic chemotherapy for relapses in and out of the liver. Accordingly, he lived for over four years. We conclude that a long-term survival in this patient can be attributable to appropriate treatment selections and timing, such as hepatic resection, TACE, HAC and ablation therapies based on changes in diagnostic imaging and tumor markers. In addition, we have to pay attention to keep good hepatic reserve in order to continue treatment for recurrences of HCC.
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PMID:[A long-term survival of the patient with hepatocellular carcinoma and advanced portal vein and bile duct tumor thrombosis successfully treated with multimodal treatments]. 1631 47

The incidence of hepatocellular carcinoma (HCC) in cirrhotic patients is increasing. Despite advances in imaging and laboratory screening which allow earlier diagnosis, the surgeon is all too often confronted with an HCC of advanced stage or arising in the setting of severe cirrhosis. Hepatic resection is still considered the treatment of choice for hepatocellular carcinoma in patients with liver cirrhosis. From 1998 to 2005, 6 patients (5 males, 1 female, age 52-70 years, mean age 64.1 years) with HCC associated severe, but well compensated liver cirrhosis (Child A-- 4 patients, Child B--2 patients) underwent 9 hepatic resection in our department. Mean tumor size was 56 mm (range 23-86 mm). Two of these lesions were in the left liver and four in the right lobe. Doppler ultrasonography was performed in all cases and CT in 3 cases to confirm the extension of the lesions. Laparoscopy was performed in 3 patients under CO2 pneumoperitoneum. The Pringle maneuver was not used. The transection of the liver parenchyma was obtained by the use of Ligasure and harmonic scalpel. Nine hepatic resections were performed: 7 segmentectomy and 2 non-anatomical resections. The resection margin was 1 cm. The mean operative time was 90 minutes (range 60-120). Mean blood loss was 250 ml and 2 patients required blood transfusion. One patient died on the tenth postoperative day from a severe respiratory distress syndrome and hepatic failure. Major morbidities occurred in three patients who developed moderate postoperative ascites, which resolved successfully with conservative treatment in two patients. Limited liver resection in cirrhotic patients with HCC is feasible with a low complication rate when careful selection criteria are followed (tumor size smaller than 8 cm, Child-Pugh A class and the good general conditions of the patients). Other medical and interventional treatments (chemoembolization, chemotherapy) can only slow the progress of HCC.
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PMID:[Liver resection for hepatocellular carcinoma in cirrhotic patients]. 1661 Jan 75

A 78-year-old man had a history of blood transfusion and hepatitis C virus-related liver cirrhosis. He was admitted to the authors' hospital with a hepatocellular carcinoma just below the right hemidiaphragm. Although the lesion was not well visualized with standard sonography, it was clearly defined by performance of sonography with intraarterial injection of carbon dioxide, allowing safe and accurate radiofrequency ablation. To increase the extent of tumor ablation, transcatheter arterial chemoembolization was performed immediately before radiofrequency ablation. By concomitant application of these two techniques, complete tumor necrosis was achieved without the need to perform additional ablation.
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PMID:Carbon dioxide-enhanced sonographically guided radiofrequency ablation plus transcatheter arterial chemoembolization for hepatocellular carcinoma. 1661 57

To report a non-fatal case of reperfusion pulmonary edema (RPE) after the removal of a hepatocellular carcinoma embolus, which had caused an acute obstruction of the tricuspid valve and pulmonary vasculature during a hepatic lobectomy. Pulmonary embolism caused by hepatocellular carcinoma embolus is extremely rare, and, in the present case, it was associated with unusual clinical features. A 69-year-old ASA II woman with hepatocellular carcinoma was presented for an elective left hepatic lobectomy. During the surgery, the tumor embolus was dislodged from the interior of the lumen of the inferior vena cava (IVC), which then drifted into the tricuspid valve area and pulmonary vasculature. The patient showed the specific signs of acute pulmonary embolism, such as a reduction in end-tidal carbon dioxide, an increase in central venous pressure, and a decrease in arterial pressure. The patient exhibited the symptoms for about 10 minutes. After this period, however, cardiovascular variables became relatively stable, even during a mechanical obstruction due to cross-clamping the pulmonary artery for embolectomy. After several hours of pulmonary embolectomy, the patient experienced an episode of RPE. The ventilatory supports for the treatment of RPE were successful, and the patient recovered without any complications. The patient's case in the present study demonstrates that pulmonary embolism may occur as a result of a hepatocellular carcinoma extending into the IVC during operative management. The anesthesiologist should be careful of the possibilities of RPE after removal of the tumor embolus.
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PMID:Reperfusion pulmonary edema after the removal of hepatocellular carcinoma embolus. 1664 60

We report a patient with hepatocellular carcinoma whose tumor thrombus was extending into the right atrium. A 55-year-old man underwent extended anterior segmental hepatectomy and removal of the tumor thrombus in the right atrium under cardiopulmonary bypass and general anesthesia using sevoflurane, nitrous oxide and oxygen. End-tidal carbon dioxide was closely monitored to detect pulmonary tumor emboli during the surgery. Intravenous fluid and blood transfusion in large volumes were necessary to avoid circulatory derangement.
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PMID:[Anesthetic management of a patient with hepatocellular carcinoma with tumor thrombosis extending into the right atrium]. 1671 16

Heme oxygenase consists of two structurally related isozymes, heme oxygenase-1 and and heme oxygenase-2, each of which cleaves heme to form biliverdin, iron and carbon monoxide. Expression of heme oxygenase-1 is increased or decreased depending on cellular microenvironments, whereas little is known about the regulation of heme oxygenase-2 expression. Here we show that hypoxia (1% oxygen) reduces the expression levels of heme oxygenase-2 mRNA and protein after 48 h of incubation in human cell lines, including Jurkat T-lymphocytes, YN-1 and K562 erythroleukemia, HeLa cervical cancer, and HepG2 hepatoma, as judged by northern blot and western blot analyses. In contrast, the expression level of heme oxygenase-1 mRNA varies under hypoxia, depending on the cell line; it was increased in YN-1 cells, decreased in HeLa and HepG2 cells, and remained undetectable in Jurkat and K562 cells. Moreover, heme oxygenase-1 protein was decreased in YN-1 cells under the conditions used, despite the induction of heme oxygenase-1 mRNA under hypoxia. The heme oxygenase activity was significantly decreased in YN-1, K562 and HepG2 cells after 48 h of hypoxia. To explore the mechanism for the hypoxia-mediated reduction of heme oxygenase-2 expression, we showed that hypoxia shortened the half-life of heme oxygenase-2 mRNA (from 12 h to 6 h) in YN-1 cells, without affecting the half-life of heme oxygenase-1 mRNA (9.5 h). Importantly, the heme contents were increased in YN-1, HepG2 and HeLa cells after 48 h of incubation under hypoxia. Thus, the reduced expression of heme oxygenase-2 may represent an important adaptation to hypoxia in certain cell types, which may contribute to the maintenance of the intracellular heme level.
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PMID:Hypoxia reduces the expression of heme oxygenase-2 in various types of human cell lines. A possible strategy for the maintenance of intracellular heme level. 1678 41

The HXeCCH...CO2 complex is studied experimentally and computationally. The complex is prepared in a low-temperature xenon matrix using UV photolysis of propiolic acid (HCCCOOH) and thermal mobilization of H atoms at 45 K. Photolysis of propiolic acid leads to the HCCH...CO2 complex as one of the photolysis products. The HCCH...CO2 complex is further photolyzed to the HCC...CO2 complex. Thermal annealing leads to the formation of HXeCCH complexed with CO2. The H-Xe stretching absorption of the HXeCCH...CO2 complex is blueshifted (+31.9 and +5.8 cm(-1)) from the value of the HXeCCH monomer in a xenon matrix. In the calculations, three HXeCCH...CO2 structures were found (one parallel and two linear structures) corresponding to the true energy minima on the potential energy surface. For the H-Xe stretching mode, the calculations give blueshifted values of +19.2 or +19.5 cm(-1) depending on the computational level [MP2/6-311++G(2d,2p) and MP2/aug-cc-pVDZ] for the parallel structure and +19.4 or +27.9 cm(-1) for one linear structure. For the second linear structure, the H-Xe stretching frequency is redshifted by -8.6 or -9.4 cm(-1) at these levels of theory. Based on the calculations, the experimental band shifted by +5.8 cm(-1) (1492.2 cm(-1)) most likely corresponds to the HXeCCH...CO2 parallel structure. The band with larger blueshift of +31.9 cm(-1) (1518.3 cm(-1)) can be due to another matrix site of the same structure or to the blueshifting linear structure.
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PMID:Matrix isolation and ab initio study of the HXeCCH...CO2 complex. 1794 55


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