Biomedical subjects

H Sakurai

Publications and source records attributed to H Sakurai.

At least 19 recordsLinked to original sources

PubMed2006

High peak reflux velocity in the proximal deep veins is a strong predictor of advanced post-thrombotic sequelae.

BACKGROUND: The presence of reflux in the femoral vein (FV) and popliteal vein (POPV) after acute deep vein thrombosis (DVT) is considered to contribute to the development of advanced post-thrombotic syndrome (PTS). However, a quantification of reflux has yet to be determined. The purpose of study was to determine the indicative parameters reflecting the progression of PTS. METHODS: Venous abnormalities were evaluated in 131 limbs out of 130 patients who completed a six-year follow-up after an acute DVT. Clinical manifestations were categorized according to the clinical, etiologic, anatomic, and pathophysiologic (CEAP) classification, and the patients were divided into two groups at a six-year follow-up point: group I, C(0-3)E(s),A(s,d,p),P(r,o), early chronic venous insufficiency (CVI); group II, C(4-6)E(s),A(s,d,p),P(r,o), advanced CVI. Venous segments were examined whether they were occluded or recanalized. The reflux parameters assessed were the diameter (cm), the reflux time (RT; s), the peak reflux velocity (PRV; cm s(-1)), and total refluxed volume, and these parameters were assessed especially in the FV and POPV at the two-year (early phase) and subsequent six-year (late phase) follow-up points after DVT. RESULTS: There were 98 limbs in group I and 33 in group II. The frequency of venous reflux was significantly higher in group II (<0.0001). In contrast, the proportion of occlusion did not differ between the groups (P = 0.138). The proportions of FV and POPV incompetence were significantly higher in group II (P < 0.0001 and P < 0.0001, respectively). In these veins, the RT did not improve the discrimination power between the two groups. In contrast, the PRV had significant discrimination power in these veins at both the two- and six-year follow-up points. In the superficial venous system, there were no significant differences in any of the determined parameters between the groups. In group II, 19 patients (58%), who had early symptoms of CVI at the two-year follow-up point, subsequently developed advanced symptoms of PTS. After calculating a suitable cutoff point using receiver operating characteristic curves analysis at the two-year follow-up point, multivariable analysis showed that a PRV of >25.4 cm s(-1) in the POPV was the strongest independent predictor of advanced CVI [odds ratio (OR) 60.32; 95% confidence interval (95CI) 43.1-1238.97, P < 0.0001]. Similarly, in the FV, a PRV of >24.5 cm s(-1) was found to be a strong predictor of advanced CVI (OR 25.77, 95CI 10.56-331.12, P < 0.0001). CONCLUSIONS: These findings suggest that the presence of a high PRV in the proximal deep veins is an independent predictor of advanced symptoms of PTS.

Aged↗

PubMed2006

Characterization of capsid-modified adenovirus vectors containing heterologous peptides in the fiber knob, protein IX, or hexon.

Adenovirus (Ad) vectors are widely used in gene therapy and in vitro/in vivo gene transfer because of their high transduction efficiency. However, Ad vector application in the gene therapy field is limited by poor transduction into cells not expressing the primary receptor, coxsackievirus and adenovirus receptor. To overcome this problem, several types of capsid-modified Ad vectors have been developed. The HI loop or C-terminus of the fiber knob, the C-terminus of the protein IX (pIX) and the hypervariable region 5 of the hexon are promising candidate locations for displaying foreign peptide sequences. In the present study, we constructed Ad vectors in which each of the above region was modified by a simple in vitro ligation-based method, and examined the characterization of each Ad vector containing the FLAG tag (DYKDDDDK) or RGD (CDCRGDCFC) peptide. Enzyme-linked immunosorbent assay examining the surface expression of foreign peptides on the virus suggested that foreign peptides are exposed on virion surfaces in all types vectors and that the hexon was the most efficiently reacted, reflecting the copy number of the modification. However, in the case of the transduction efficiency of Ad vectors containing the RGD peptides, the modification of pIX and the hexon showed no effect. The modification of the HI loop of the fiber knob was the most efficient, followed by the modification of the C-terminus region of the fiber knob. These comparative analyses, together with a simple construction method for each modified Ad vector, could provide basic information for the generation of capsid-modified Ad vectors.

Adenoviridae↗

PubMed2006

Measurement of excited states in (40)Si and evidence for weakening of the N=28 shell gap.

Excited states in (40)Si have been established by detecting gamma rays coincident with inelastic scattering and nucleon removal reactions on a liquid hydrogen target. The low excitation energy, 986(5) keV, of the 2(1)(+) state provides evidence of a weakening in the N=28 shell closure in a neutron-rich nucleus devoid of deformation-driving proton collectivity.

Journal Article↗

PubMed2006

Observation of strong low-lying E1 strength in the two-neutron halo nucleus 11Li.

An exclusive measurement has been made of the Coulomb dissociation of the two-neutron halo nucleus 11Li at 70 MeV/nucleon at RIKEN. Strong low-energy (soft) E1 excitation is observed, peaked at about Ex = 0.6 MeV with B(E1) = 1.42(18) e2fm2 for Erel < or = 3 MeV, which was largely missed in previous measurements. This excitation represents the strongest E1 transition ever observed at such low excitation energies. The spectrum is reproduced well by a three-body model with a strong two-neutron correlation, which is further supported by the E1 non-energy-weighted cluster sum rule.

Journal Article↗

PubMed2006

Comparison of manual compression release with distal pneumatic cuff maneuver in the ultrasonic evaluation of superficial venous insufficiency.

BACKGROUND: Venous reflux can be elicited either manually or by pneumatic tourniquet, and previous studies did not indicate any significant difference between these manoeuvres in patients with superficial venous insufficiency (SVI). PURPOSE: To investigate if two methods correlate in patients with CVI. MATERIALS AND METHODS: Venous reflux was studied in 94 venous segments of 57 limbs in 52 consecutive patients with SVI. Limbs were divided into two groups: group I (CEAP C2-C3) and group II (CEAP C4-C6). A colour duplex scanner was used to determine quantitative venous reflux at the sapheno-femoral junction (SFJ), at the sapheno-popliteal junction (SPJ), and in the greater saphenous vein in the thigh (GSV). Patients received both manual compression and cuff deflation method in eliciting venous reflux. The parameters assessed were the duration of reflux (second) and the peak reflux velocity (cm/s). STATISTICS: Paired t-test was used to evaluate differences between the two methods. Statistical significance was recorded when the p-value was <0.05. Bland and Altman plot was also used to assess the agreement of the same measurement. RESULTS: There were 58 venous segments in group I and 36 in group II. In group I, there were no significant differences in the duration of reflux at the SFJ, SPJ, and in the GSV. On the contrary, peak reflux velocity was found to be significantly higher at the SFJ and in the GSV (p=0.022 and 0.006, respectively). In group II, there was no significant difference in the duration of reflux at the SFJ and SPJ between the two methods. On the contrary, manual compression maneuver produced significantly higher peak reflux velocity than at the SFJ and in the GSV (p=0.023 and 0.002, respectively). Bland and Altman plot analysis, manual compression method displayed a relatively good agreement with cuff deflation manoeuvre both in group I and group II. In contrast, concerning the peak reflux velocity, relative wide limits of agreement were found between the two methods. CONCLUSIONS: Unlike previously published reports, our results lead to apparent discrepancies in the quantitative evaluation of venous reflux using different methodology.

Adult↗

PubMed2006

Solution equilibrium characterization of insulin-mimetic Zn(II) complexes.

Solution speciation (stoichiometry and stability constants) of the insulin mimetic Zn(II) complexes of several bidentate ligands with (O,O), (N,O) or (S,O) coordination modes have been determined by pH-metry at 25 degrees Celsius and I=0.2M (KCl). All ligands were found to coordinate in a bidentate way forming mono, bis and tris complexes, besides a mixed hydroxo bis complex ZnL(2)(OH) detected in the slightly basic pH range together with the tris complex. Relationships between the stability data, lipophilicity of the complexes and earlier biological data are evaluated. The validity of the linear free energy relationships (LFER) between the proton and Zn(II) complexes and also between the VO(IV) and Zn(II) complexes is tested.

Hydrogen-Ion Concentration↗

PubMed2006

Vanishing N = 20 shell gap: study of excited states in (27,28)Ne.

This Letter reports on the (1)H((28)Ne, (28)Ne) and (1)H((28)Ne, (27)Ne) reactions studied at intermediate energy using a liquid hydrogen target. From the cross section populating the first 2(+) excited state of (28)Ne, and using the previously determined BE(2) value, the neutron quadrupole transition matrix element has been calculated to be M(n)=13.8 +/- 3.7 fm(2). In the neutron knockout reaction, two low-lying excited states were populated in (27)Ne. Only one of them can be interpreted by the sd shell model while the additional state may intrude from the fp shell. These experimental observations are consistent with the presence of fp shell configurations at low excitation energy in (27,28)Ne nuclei caused by a vanishing N=20 shell gap at Z=10.

Journal Article↗

PubMed2006

A new approach to measuring high-resolution magnetic Compton profiles.

It is demonstrated that long-term stability in the polarization of incident photons delivered from an insertion device makes it possible to measure magnetic Compton profiles with a momentum resolution of 0.15 atomic units or better, without employing a solid-state detector and the traditional method of reversing the external magnetic field or the handedness of the polarization of incident photons in an asynchronous cycle with a short period of tens to hundreds of seconds.

Journal Article↗

PubMed2006

The utility of quantitative calf muscle near-infrared spectroscopy in the follow-up of acute deep vein thrombosis.

BACKGROUND: To investigate patterns of venous insufficiency and changes in calf muscle deoxygenated hemoglobin (HHb) levels after an acute deep vein thrombosis (DVT). METHODS: A total of 78 limbs with an acute DVT involving 156 anatomic segments were evaluated with duplex scanning and near-infrared spectroscopy (NIRS) at 1, 3, 6 and 12 months. Venous segments were examined whether they were occluded, partially recanalized, and totally recanalized, and the development of venous reflux was noted. The NIRS was used to measure calf muscle HHb levels. Calf venous blood filling index (HHbFI) was calculated on standing, then the calf venous ejection index (HHbEI), and the venous retention index (HHbRI) were obtained after exercise. RESULTS: The segments investigated were the common femoral vein (CFV; 38 segments), femoral vein (FV; 37), popliteal vein (POPV; 44), and calf veins (CV; 37). At 1 year, thrombi had fully resolved in 67% of the segments, 27% remained partially recanalized, 6% were occluded. The venous occlusion was predominant in the FV (24%) at 1 year. On the contrary, rapid recanalization was obtained in CV than proximal veins at each examination (P < 0.01). Venous reflux was predominant in POPV (55%), followed by FV (19%), and no reflux was found in CV. At 1 year, the HHbFI in POPV reflux patients was significantly higher than those with resolution (0.19 +/- 0.14, 0.11 +/- 0.05 microm s, P = 0.009, respectively). Similarly, there was a significant difference in the HHbRI between the two groups (3.08 +/- 1.91, 1.42 +/- 1.56, P = 0.002, respectively). In patients with FV occlusion, the value of HHbRI was significantly higher than those with complete resolution (2.59 +/- 1.50, 1.42 +/- 1.56, P = 0.011, respectively). CONCLUSIONS: The lower extremity venous segments show different proportions of occlusion, partial recanalization, and total recanalization. The CV shows more rapid recanalization than proximal veins. The NIRS-derived HHbFI and HHbRI could be promising parameters as the overall venous function in the follow-up of acute DVT. These findings might be very helpful for physician in detecting patients who require much longer follow-up studies.

Acute Disease↗

PubMed2006

No meaningful increase in urinary tubular dysfunction markers in a population with 3 microg cadmium/g creatinine in urine.

The critical Cd exposure level to induce tubular dysfunctions is a focus of public concern among general populations in Japan. To answer this question, one group each (about 1000 adult women/area) in nonpolluted areas with high (Area H) and low Cd exposure (Area L) was obtained, and 742 strictly age-matched pairs of never-smoking adult women were selected for comparison. Cd, alpha1-MG (microglobulin) and beta2- MG in urine were taken as markers of exposure and tubular dysfunction, respectively. Geometric mean Cd levels as corrected for creatinine (Cdcr) was greater than three times higher in Area H (2.8 microg/g cr) than in Area L (0.8 microg/g cr). Nevertheless, beta2-MGcr did not differ between the two areas (125 microg/g cr for Area H vs 118 microg/g cr for Area L). alpha1-MGcr was only marginally higher in Area H (2.8 mg/g cr) than in Area L (2.1 mg/g cr), with no biomedical significance. Results were essentially the same when analyses were conducted with noncorrected observed values or values corrected for a specific gravity. Thus, the effects of Cd exposure in Area H on renal tubular function should be essentially nil.

Adult↗

PubMed2006

[Catamenial pneumothorax].

We report 3 cases of catamenial pneumothorax, with review of the literatures. Case 1: A 38-year-old female had recurrent right-sided pneumothorax in February 2001. Videothoracoscopic visualization showed multiple small fenestrations in central tendon of diaphragm. A partial diaphragmatic resection including the lesions was performed. She received hormone therapy postoperatively. Case 2: A 40-year-old female with past history of ovarian endometriosis had recurrent right-sided pneumothorax in 1993. During the operation, multiple diaphragmatic fenestrations and bullae of right middle and lower lobes were identified. The lesions were resected and postoperative hormone therapy was performed for 6 months. In 1997, right-sided pneumothorax recurred. She underwent surgical procedure due to prolonged air leakage from the right lung. During the operation, a diaphragmatic fenestration and bulla of apex of right upper lobe of the lung were visualized. Diaphragm was reefed and bulla was resected. After that, she had no recurrence of pneumothorax. Case 3: A 39-year-old female had recurrent right-sided pneumothorax in 2003. Under video-assisted thoracoscopic surgery, multiple fenestrations of central tendinous diaphragm were identified. Diaphragmatic partial resection was performed. Postoperatively, she received hormone therapy for 6 months. After hormone therapy, she suffered from recurrent pneumothorax, and underwent an operation. During the operation, she had endometriosis of visceral pleura without diaphragmatic fenestration. Once again, she received postoperative hormone therapy. Catamenial pneumothorax is a rare disease, and the definite etiology has not been clarified. A combination of both surgical and hormone therapy is useful for treatment.

Adult↗

PubMed2005

Orally active antioxidative copper(II) aspirinate: synthesis, structure characterization, superoxide scavenging activity, and in vitro and in vivo antioxidative evaluations.

Ever since it was proposed that reactive oxygen species (ROS) are involved in the pathogeneses of various diseases, superoxide dismutase (SOD)-mimetic complexes have been intensively studied. We prepared copper(II) aspirinate [Cu2(asp)4] from Cu(II) and aspirin, which has been in use for many years as an antipyretic, an analgesic, and an anti-inflammatory agent. However, Cu2(asp)4 has been found to have additional activities, including anti-inflammatory, antiulcer, anti-ischemic/reperfusion agent, anticancer, antimutagenic, and antimicrobial activities. The activity of copper salicylate [Cu(sal)2] was also compared with that of Cu2(asp)4. The structure of the Cu2(asp)4 was determined using X-ray structure analysis. Its SOD-mimetic activity was determined using cytochrome c, electron spin resonance (ESR) spectroscopy, and ESR spin trap methods. The activity of Cu2(asp)4 was slightly greater than CuSO4 and copper acetate [Cu(ace)2] and slightly less than that of Cu(sal)2. The in vitro antioxidant activity, evaluated in human epithelial or transformed neoplastic keratinocyte cells, HaCaT, and normal dermal fibroblasts in terms of cell survival following ultraviolet B (UVB) irradiation, was significantly increased in the presence of Cu2(asp)4, Cu(sal)2, and CuSO4. Further, ROS generation following UVA irradiation in the skin of hairless mice following oral treatment with Cu2(asp)4 for three consecutive days was significantly suppressed compared to the vehicle- or Cu(ace)2-treated mice. On the basis of these results, Cu2(asp)4 was observed to be a potent antioxidative compound possessing antioxidative activity in biological systems. In conclusion, Cu2(asp)4 is a potent antioxidative agent that may be useful for future treatment of diseases resulting from ROS.

Administration, Oral↗

PubMed2005

Influence of low-frequency massage device on transdermal absorption of ionic materials.

The influence of a low-frequency massage device on transdermal absorption of sodium benzoate, ketoprofen and diclofenac sodium was investigated in rats. Electrode pads spread with a hydroxypropyl cellulose gel containing the drug model were placed on excised skin in vitro. The transdermal permeation studies were carried out in the treatment group with the pulse applied through electrode pads spread with the gel, the pretreatment group with the gel applied after the application of the pulse and in the control group in which the gel was applied without the pulse. In vivo, transdermal absorption of ketoprofen was examined in the same groups used for the in vitro study. The pharmacokinetics of ketoprofen in plasma after intravenous injection was also studied. The treatment group showed higher cumulative permeated amounts of the drug models than the control in vitro. However, the enhancing effect was not observed in the pretreatment group. In vivo, the plasma ketoprofen level increased temporarily after the pulse was applied and then increased gradually as compared with the control. Since the distribution of ketoprofen from the central to the peripheral compartment was enhanced by the pulse in the injection study, enhancement of the biodistribution of ketoprofen by the low-frequency pulse was suggested.

Administration, Cutaneous↗

PubMed2005

Low-level cadmium exposure in Toyama City and its surroundings in Toyama prefecture, Japan, with references to possible contribution of shellfish intake to increase urinary cadmium levels.

OBJECTIVES: This study was initiated to examine if exposure to cadmium (Cd) was high also outside of the previously identified Itai-itai disease endemic region in the Jinzu River basin in Toyama prefecture in Japan. METHODS: Morning spot urine samples were collected in June-August 2004 from 651 adult women (including 535 never-smokers) in various regions in Toyama prefecture, and subjected to urinalyses for cadmium (Cd), alpha1-microglobulin (alpha1-MG), beta2-microglobulin (beta2-MG), N-acetyl-beta-D-glucosaminidase (NAG), specific gravity (SG or sg) and creatinine (CR or cr). Three months later, the second urine samples were collected from those with elevated Cd in urine (e.g., > or =4 microg/g cr), together with answers to questionnaires on shellfish consumption. RESULTS: The geometric mean (GM) Cd, alpha1-MG, beta2-MG and NAG (after correction for CR) for the total participants were 2.0 microg/g cr, 2.4 mg/g cr, 104 microg/g cr and 2.8 units/g cr, respectively; further analysis with never-smoking cases only did not induce significant changes in these parameters. Analyses of the second urine samples from the high Cd subjects showed that there was substantial decrease (to about a half) in Cd in the 3-month period, and that the decrease was accompanied by reduction in alpha1-MG and NAG (beta2-MG did not show elevation even in the first samples). The urinalysis results in combination with the results of the questionnaire survey suggest that the high urinary Cd was temporary and might be induced by intake of shellfish that is edible whole. CONCLUSIONS: The overall findings appear to suggest that Cd exposure in Toyama populations (outside of the Itai-itai disease endemic region) was at the levels commonly observed on the coast of the Sea of Japan, and that the Cd level in urine might be modified by the intake of some types of seafood. Further studies are necessary to elucidate the relation of urinary Cd with seafood intake.

Acetylglucosaminidase↗

PubMed2005

Smoking-induced increase in urinary cadmium levels among Japanese women.

OBJECTIVE: To examine if cigarette smoking will induce elevation in cadmium (Cd) in urine. METHODS: Information on smoking habits, and urinary levels of cadmium (Cd-U), alpha(1)-microglobulin (alpha(1)-MG), beta(2)-microglobulin (beta(2)-MG), creatinine (CR or cr), and urine specific gravity (SG or sg) was cited from a combination of three previously established databases on adult Japanese women. After exclusion of those with unclear answers on smoking habits (412 cases), the combination (12,846 cases) gave 11,092, 1420 and 334 cases of never, current and former smokers, respectively, for present statistical analyses. RESULTS: Multiple regression analyses taking Cd-U as a dependent variable and 11 regions of urine collection, age and smoking habits as independent variables showed that age and regions were powerful confounders in the analysis for the effects of smoking on Cd-U. To exclude the confounding effects, current and former smokers were paired with age- and region-matched never smoking controls in subsequent analyses. In addition, former smokers were paired with age- and region-matched current smokers. The comparison of the paired cases showed that Cd-U for current smokers was significantly higher than that for never smokers. The levels for former smokers were however not higher than the levels for never smokers. When classified by the number of cigarettes consumed per day, Cd-U for current smokers increased dependently to the number of cigarettes (about 0.09 microg/cigarette/day) with leveling off at 15 or more cigarettes. There was a subtle cigarette dose-dependent increase in alpha(1)-MG, but the increase was insignificant in case of beta(2)-MG. Estimation of the amount of Cd absorbed due to cigarette smoking followed by comparison with the increase in Cd-U suggested that almost all Cd absorbed will be excreted into urine. CONCLUSIONS: Among currently smoking Japanese women, cadmium in urine increased in a manner dependent to the number of cigarettes consumed daily. Thus, smoking is a confounder of Cd-U evaluation even among the population with relatively high dietary Cd burden.

Adult↗

PubMed2005

Decreases in urine specific gravity and urinary creatinine in elderly women.

OBJECTIVE: To examine the effects of aging on urinary levels of creatinine (CR) and urine specific gravity (SG) among women in a large-scale epidemiology survey. METHODS: Data on CR and SG in urine, together with smoking habits and menopausal status, were selected from previously established databases and combined with the results of supplemental sample collection. In total, CR and SG data were available for 11,090 never-smoking women (total group; 29-80 years of age); a subgroup of 1,851 women who lived in Kyoto was also selected from the total group. Data from the two groups were subjected to statistical analyses. In statistical evaluation, SG was converted to factor G, which was defined as (SG-1.000)x1,000. RESULTS: Classification by decade of years of age showed that both CR and SG decreased steadily as a function of advancement in age over 30 years, both in the total group and in the Kyoto subgroup, showing high reproducibility of the observation on a whole-country basis and on a local basis. When the levels at 80 years of age were compared with those at 30 years, there was an approximately 60% and 30% decrease in CR and factor G, respectively. Thus, the effects of aging were more marked on CR than on factor G (and therefore on SG). Menopause appeared to be an influential factor in the reduction of CR and SG, separately from aging itself. CONCLUSIONS: Urinary levels of creatinine and, to a lesser extent, urine specific gravity, steadily decreased as a function of ages of over 30 years in women.

Adult↗

PubMed2005

Effects of aging on cadmium and tubular dysfunction markers in urine from adult women in non-polluted areas.

OBJECTIVES: The objectives of the present analyses were to examine if Cd and tubular dysfunction marker levels in urine show age-dependent changes among women who lived in areas with no known cadmium (Cd) pollution in Japan, and if the trends would be further modified by correction of analyte concentration in terms of urinary creatinine (CR or cr) or urine specific gravity (SG or sg). METHODS: The results of urinalysis for Cd, alpha(1)-microglobulin (alpha(1)-MG), beta(2)-microglobulin (beta(2)-MG), and N-acetyl-beta-D: -glucosaminidase (NAG) concentrations together with CR and SG were cited from previously established databases. A majority of urine samples were collected in 2000-2002 from adult women (mostly at 40-60 years of age) in various areas in Japan, and the collection was supplemented by cases of > or =60-year-old women in 2003. In total, 11,090 never-smoking cases were subjected to statistical analysis. The values as observed (e.g., Cd(ob)), together with after correction for CR (e.g., Cd(cr)) or SG (e.g., Cd(sg)), were examined by linear regression analysis after logarithmic conversion. RESULTS: The geometric mean (GM) values for Cd were 1.10 microg/l (as observed) or 1.32 microg/g cr (after correction for creatinine concentration). No increases were found in the levels of alpha(1)-MG, beta(2)-MG or NAG on a group basis, in agreement with the conditions that there was no known environmental pollution with Cd in the sampling areas. There were almost linear increases in logarithm of Cd, alpha(1)-MG, beta(2)-MG and NAG concentrations as age advanced. As CR, and to a lesser extent SG, also decreases steadily throughout life, the correction of the analyte concentrations for urine density induced substantial increases in the analyte values; i.e., the correction by CR and SG induced amplification of the increases by two- and 1.4-times, respectively, compared with the increase in non-corrected observed values. CONCLUSIONS: There were age-related increases in Cd and tubular dysfunction markers in urine among women in areas with no known Cd pollution. The increase was amplified two- or 1.4-times when CR or SG correction was applied, respectively. The observation suggests that care should be practiced in applying CR or SG correction, especially when evaluation of Cd exposure and resulting health effects is made among elderly populations.

Aging↗

PubMed2005

Selective inhibition of TNF-alpha-induced activation of mitogen-activated protein kinases and metastatic activities by gefitinib.

We have reported that the selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, gefitinib ('Iressa', ZD1839), suppressed intrahepatic metastasis of hepatocellular carcinoma CBO140C12 cells. In this study, we focused on the tumour necrosis factor-alpha (TNF-alpha) signalling pathways. Real-time reverse transcription-polymerase chain reaction showed that TNF-alpha mRNA was expressed in large quantities in the implanted tumour. Gefitinib inhibited EGF- but not hepatocyte growth factor (HGF)-induced activation of mitogen-activated protein kinase (MAPK) cascades, suggesting selectivity of the inhibitor. However, gefitinib inhibited the TNF-alpha-induced activation of MAPKs and Akt. In addition, TNF-alpha-induced metastatic properties including adhesion to fibronectin, mRNA expression of integrin alpha v, production of matrix metalloproteinase-9 and invasion were inhibited by gefitinib without affecting cell proliferation. Furthermore, the TNF-alpha-induced responses except for NF-kappaB activation were blocked by metalloprotease inhibitors, suggesting that gefitinib inhibited the transactivation of EGFR induced by TNF-alpha. These results suggest that the TNF-alpha signalling pathway is a possible target of gefitinib in suppressing the intrahepatic metastasis of hepatocellular carcinoma.

Animals↗