School-based psychoeducation and storytelling: Associations with long-term mental health in adolescent survivors of the Wenchuan earthquake.

AIMS: We explored the factors promoting long-term mental health among adolescent survivors of the 2008 Wenchuan earthquake in China. We examined the associations of their long-term mental health with disaster-related storytelling and school-based psychoeducation, and of school-based psychoeducation with disaster-related storytelling. METHODS: A secondary school-based cross-sectional survey was conducted 6 years after the disaster. Participants with traumatic experiences such as injury, loss, witnessing someone's death/injury and home destruction (N = 1028, mean age 15, standard deviation 1.38, male 51%) were eligible. Mental health/disaster education (MHE/DE) was defined as taking one or more lessons in MHE and/or DE at school since the earthquake. Experiences of storytelling about the disaster involved expressing distressing memories and feelings regarding the earthquake since the disaster happened, according to four groups: never expressed distressing memories and feelings, expressed them through writing/drawing, expressed them through talking to lay supporters and expressed them through talking to health professionals. Analysis of covariance was used to compare mean scores on five selected subscales of the Symptom Checklist-90 (SCL-90), the Athens Insomnia Scale (AIS) and the Psychotic-Like Experiences (PLEs) scale among the four storytelling groups. Linear regression analysis was used to identify the relationships between MHE/DE and current mental health as measured by the SCL-90, AIS and PLEs. The relationship between education and storytelling was probed by χ2 test. RESULTS: The talked-to-lay-supporters group showed better mental health on the SCL-90 (p ⩽ 0.001), AIS (p < 0.001) and PLEs (p = 0.004), while the consulted-health-professionals group showed worse mental health on the three dimensions of the SCL-90: depression (p = 0.05), anxiety (p = 0.02) and fear (p = 0.04), and on PLEs (p = 0.02) compared with the never-expressed group. MHE and DE were inversely associated with SCL-90, AIS and PLE scores. Participants who received these forms of education talked about their disaster experiences to lay supporters more than those who did not. CONCLUSIONS: MHE and DE at school may promote adolescents' mental health after a disaster. Experience of storytelling about the disaster to lay supporters may be helpful for long-term psychological recovery, and may be a potential mediating factor for school-based education and better mental health. Because of the cross-sectional nature of this study, causality cannot be inferred; therefore, further prospective intervention studies are needed to elucidate the effect of these factors on adolescent survivors' mental health.

Intermetallic: A Pseudoelement for Catalysis.

A clear correlation between electronic structure and CO2 selectivity for steam reforming of methanol (SRM) was obtained with PdZn, PtZn, NiZn, and PdCd intermetallics on the basis of experiments and calculations. In order to rule out the effects of oxide supports, the intermetallic powders were simply prepared by alloying in an arc furnace followed by crushing in a mortar. PdZn and PdCd exhibit valence electronic densities of states similar to that of Cu and significant chemical shifts (larger than 1 eV) of Pd 3d states with respect to pure Pd, as verified by high-resolution hard X-ray photoelectron spectroscopy (HXPS) measurements and density functional theory (DFT) calculations. Consequently, they show the similar high selectivity of CO2 for the SRM reaction. However, this is not the case for PtZn and NiZn because of the slight differences in their valence electronic structures from that of PdZn. The interval between the Fermi level and the top of the d band is closely related to the selectivity of CO2 for the SRM: the larger the interval is, the higher is the selectivity of CO2. According to DFT calculations for bulk PdZn performed by Chen et al. ( Phys. Rev. B 2003 , 68 , 075417 ), the (111) and (100) surfaces exposing Zn and Pd in an equimolar ratio are more stable than the (001) or (110) surfaces terminated by alternative Zn or Pd layers. First-principles slab calculations for PdZn, PtZn, and NiZn show that bond breaking on the surface leads to a reduction in the d bandwidth but that the d band for stable (111) or (100) surfaces remains essentially unchanged from that of the bulk. It is intriguing that PdZn and PdCd do not contain Cu but show similar valence electronic structure and catalytic selectivity, and hence, a concept is proposed where PdZn and PdCd are regarded as pseudoelements of Cu. The basis of this concept is like electronic structure, like catalysis, which has been demonstrated by experiments and calculations. This is a logical way to enable us to look for new catalysts in which precious metals are partially or completely replaced by base metals. We do not expect that this concept can be applied to all catalytic reactions, but this approach is one of most promising ways to derive a better understanding of the origin of catalytic mechanisms and eventually allow us to design useful catalysts intentionally in the future. This Account reviews the authors' published works on this topic.

S-1 as adjuvant chemotherapy for stage III colon cancer: a randomized phase III study (ACTS-CC trial).

BACKGROUND: S-1 is an oral fluoropyrimidine whose antitumor effects have been demonstrated in treating various gastrointestinal cancers, including metastatic colon cancer, when administered as monotherapy or in combination chemotherapy. We conducted a randomized phase III study investigating the efficacy of S-1 as adjuvant chemotherapy for colon cancer by evaluating its noninferiority to tegafur-uracil plus leucovorin (UFT/LV). PATIENTS AND METHODS: Patients aged 20-80 years with curatively resected stage III colon cancer were randomly assigned to receive S-1 (80-120 mg/day on days 1-28 every 42 days; four courses) or UFT/LV (UFT: 300-600 mg/day and LV: 75 mg/day on days 1-28 every 35 days; five courses). The primary end point was disease-free survival (DFS) at 3 years. RESULTS: A total of 1518 patients (758 and 760 in the S-1 and UFT/LV group, respectively) were included in the full analysis set. The 3-year DFS rate was 75.5% and 72.5% in the S-1 and UFT/LV group, respectively. The stratified hazard ratio for DFS in the S-1 group compared with the UFT/LV group was 0.85 (95% confidence interval: 0.70-1.03), demonstrating the noninferiority of S-1 (noninferiority stratified log-rank test, P < 0.001). In the subgroup analysis, no significant interactions were identified between the major baseline characteristics and the treatment groups. CONCLUSION: Adjuvant chemotherapy using S-1 for stage III colon cancer was confirmed to be noninferior in DFS compared with UFT/LV. S-1 could be a new treatment option as adjuvant chemotherapy for colon cancer. CLINICALTRIALSGOV: NCT00660894.

The use of arthrography in the diagnosis of temporomandibular joint synovial chondromatosis.

Synovial chondromatosis (SC) involving the temporomandibular joint (TMJ) is very rare and can occur in either or both cavities. Differentiation of the affected cavity in SC is therefore as important as making the diagnosis. This report presents a case of SC in which both cavities were thought to be affected, but arthrography using cone beam CT (CBCT) allowed us to see that involvement was limited to the superior joint cavity. In addition, we describe the usefulness of arthrographic CBCT for diagnosis and treatment planning in SC of the TMJ.

Safety of UFT/LV and S-1 as adjuvant therapy for stage III colon cancer in phase III trial: ACTS-CC trial.

BACKGROUND: The Adjuvant Chemotherapy Trial of TS-1 for Colon Cancer (ACTS-CC) is a phase III trial designed to validate the non-inferiority of S-1 to UFT/leucovorin (LV) as postoperative adjuvant chemotherapy for stage III colon cancer. We report the results of a planned safety analysis. METHODS: Patients aged 20-80 years with curatively resected stage III colon cancer were randomly assigned to receive UFT/LV (UFT, 300 mg m(-2) per day as tegafur; LV, 75 mg per day on days 1-28, every 35 days, 5 courses) or S-1 (80, 100, or 120 mg per day on days 1-28, every 42 days, 4 courses). Treatment status and safety were evaluated. RESULTS: Of 1535 enrolled patients, a total of 1504 (756 allocated to S-1 and 748 to UFT/LV) were analysed. The completion rate of protocol treatment was 77% in the S-1 group and 73% in the UFT/LV group. The overall incidence of adverse events (AEs) were 80% in S-1 and 74% in UFT/LV. Stomatitis, anorexia, hyperpigmentation, and haematological toxicities were common in S-1, whereas increased alanine aminotransferase and aspartate aminotransferase were common in UFT/LV. The incidences of grade 3 AEs were 16% and 14%, respectively. CONCLUSION: Although AE profiles differed between the groups, feasibility of the protocol treatment was good. Both S-1 and UFT/LV could be safely used as adjuvant chemotherapy.

Use of human stem cell derived cardiomyocytes to examine sunitinib mediated cardiotoxicity and electrophysiological alterations.

Sunitinib, an oral tyrosine kinase inhibitor approved to treat advanced renal cell carcinoma and gastrointestinal stroma tumor, is associated with clinical cardiac toxicity. Although the precise mechanism of sunitinib cardiotoxicity is not known, both the key metabolic energy regulator, AMP-activated protein kinase (AMPK), and ribosomal S 6 kinase (RSK) have been hypothesized as causative, albeit based on rodent models. To study the mechanism of sunitinib-mediated cardiotoxicity in a human model, induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) having electrophysiological and contractile properties of native cardiac tissue were investigated. Sunitinib was cardiotoxic in a dose-dependent manner with an IC50 in the low micromolar range, observed by a loss of cellular ATP, an increase in oxidized glutathione, and induction of apoptosis in iPSC-CMs. Pretreatment of iPSC-CMs with AMPK activators AICAR or metformin, increased the phosphorylation of pAMPK-T172 and pACC-S79, but only marginally attenuated sunitinib mediated cell death. Furthermore, additional inhibitors of AMPK were not directly cytotoxic to iPSC-CMs up to 250 µM concentrations. Inhibition of RSK with a highly specific, irreversible, small molecule inhibitor (RSK-FMK-MEA) did not induce cytotoxicity in iPSC-CMs below 250 µM. Extensive electrophysiological analysis of sunitinib and RSK-FMK-MEA mediated conduction effects were performed. Taken together, these findings suggest that inhibition of AMPK and RSK are not a major component of sunitinib-induced cardiotoxicity. Although the exact mechanism of cardiotoxicity of sunitinib is not known, it is likely due to inhibition of multiple kinases simultaneously. These data highlight the utility of human iPSC-CMs in investigating the potential molecular mechanisms underlying drug-induced cardiotoxicity.

Establishment of temporomandibular joint puncture technique in rats using in vivo micro-computed tomography (R_mCT®).

The aim of the report was to establish puncture techniques for the temporomandibular joint (TMJ) cavity in rats. The experimental sample comprised 30 male Sprague-Dawley rats. Under general anaesthesia the superior joint cavity of the rat was punctured either laterally (lateral puncture technique (LPT), n = 11), anteriorly (anterosuperior puncture technique (ASPT), n = 13) or anteroinferior puncture technique (AIPT), n = 6) using a 27-gauge needle. After the tip of the needle was confirmed by micro-CT (R-mCT®, Rigaku, Tokyo, Japan) located on the mandibular fossa, 0.05 ml of contrast media was injected under micro-CT fluoroscopic guidance. After confirmation that the joint cavity was filled with contrast media, micro-CT imaging was carried out. The puncture for LPT was accurate in 5 of the 11 animals. The ASPT was accurate in all 13 animals. The AIPT punctured 3 of the 6 animals. Furthermore, the ASPT and AIPT demonstrated improved preservation of the needle; it was harder to detach the needle, which led to greater stability. These results suggest that ASPT assisted by R-mCT® is useful for basic research, including drug discovery and pathogenesis of TMJ diseases.

Three-body nonmesonic weak decay of the (Lambda)12C hypernucleus.

We have measured the branching ratio of the three-body process in the nonmesonic weak decay of Lambda12C to be 0.29+/-0.13. This result was obtained by reproducing the nucleon and the nucleon pair yields introducing a measured final state interaction. At the same time, we have determined the absolute decay widths, Gamma(n) and Gamma(p), along with Gamma2N, whose relative ratio has been a long-standing puzzle. Including the three-body process, we have successfully reproduced the nucleon energy distribution, the coincidence two-nucleon angular correlation, and the momentum sum distribution simultaneously.

Diagnostic accuracy of microcomputed tomography for osseous abnormalities in the rat temporomandibular joint condyle.

OBJECTIVES: Our aim was to investigate the diagnostic accuracy of in vivo micro-CT for osseous abnormalities of the rat temporomandibular joint (TMJ) condyle, using macroscopic observations as the "gold standard". METHODS: A 30 TMJ arthritis model was prepared by injecting inflammatory complete Freund's adjuvant (CFA) into one side of the TMJ cavities of rats. The TMJ condyles were then imaged using micro-CT. The samples were macroscopically evaluated for osseous abnormalities, including erosions, osteophytes, flattening and concavity. The micro-CT images were independently assessed for abnormalities using the same criteria. Images in three planes were produced using the micro-XYZ technique with the micro-CT equipment. RESULTS: According to the macroscopic observations, 26 of the 60 rat condyles showed osseous abnormalities. The micro-XYZ images detected abnormalities in 25 of the condyles. The condyle diagnostic accuracy of micro-CT was 0.98, the sensitivity was 0.96 and the specificity was 1.0. CONCLUSIONS: Good diagnostic results were obtained using micro-CT. It is therefore an effective technique for the evaluation of osseous abnormalities in the rat TMJ condyle.

Meiotic chromosomes move by linkage to dynamic actin cables with transduction of force through the nuclear envelope.

Chromosome movement is prominent during meiosis. Here, using a combination of in vitro and in vivo approaches, we elucidate the basis for dynamic mid-prophase telomere-led chromosome motion in budding yeast. Diverse findings reveal a process in which, at the pachytene stage, individual telomere/nuclear envelope (NE) ensembles attach passively to, and then move in concert with, nucleus-hugging actin cables that are continuous with the global cytoskeletal actin network. Other chromosomes move in concert with lead chromosome(s). The same process, in modulated form, explains the zygotene "bouquet" configuration in which, immediately preceding pachytene, chromosome ends colocalize dynamically in a restricted region of the NE. Mechanical properties of the system and biological roles of mid-prophase movement for meiosis, including recombination, are discussed.

Dosimetric evaluation of nuclear interaction models in the Geant4 Monte Carlo simulation toolkit for carbon-ion radiotherapy.

We tested the ability of two separate nuclear reaction models, the binary cascade and JQMD (Jaeri version of Quantum Molecular Dynamics), to predict the dose distribution in carbon-ion radiotherapy. This was done by use of a realistic simulation of the experimental irradiation of a water target. Comparison with measurement shows that the binary cascade model does a good job reproducing the spread-out Bragg peak in depth-dose distributions in water irradiated with a 290 MeV/u (per nucleon) beam. However, it significantly overestimates the peak dose for a 400 MeV/u beam. JQMD underestimates the overall dose because of a tendency to break a nucleus into lower-Z fragments than does the binary cascade model. As far as shape of the dose distribution is concerned, JQMD shows fairly good agreement with measurement for both beam energies of 290 and 400 MeV/u, which favors JQMD over the binary cascade model for the calculation of the relative dose distribution in treatment planning.

Comparison of image validity between cone beam computed tomography for dental use and multidetector row helical computed tomography.

OBJECTIVES: To evaluate and compare the image validity of a cone beam CT machine for dental use (3DX) and the latest medical CT system, multidetector row helical CT (MDCT). METHODS: A dried right maxilla of an Asian adult was used as a phantom. It was cut from the zygomatic process towards the midline, parallel to the midline plane, into eight slices of 2 mm thickness. This phantom was imaged with the 3DX and MDCT machines. Images were evaluated by comparing them with one selected bone slice from the phantom. In this comparison, two types of MDCT images were used: one with the window level (WL) and window width (WW) suitable for observing teeth (MDCT tooth image), and the other appropriate for observing bone (MDCT bone image). Three dentists and one radiographer then used our reported subjective five-level scale to evaluate and compare images generated by the two systems in terms of validity. Cancellous bone as well as enamel, dentin, pulp cavity, periodontal ligament space, lamina dura and overall impression were evaluated. RESULTS: Statistically significant differences (P<0.05) were found for almost all observation items. Our subjective evaluation clarified that 3DX was superior to MDCT in terms of image validity. Few significant intra- or interevaluator errors were found. CONCLUSIONS: Our subjective evaluation of image validity clarified 3DX as being superior to MDCT. Taken together with the low skin dose we previously reported for 3DX, the results demonstrate 3DX to be beneficial for imaging diagnosis of hard tissues in the maxillofacial region.

Prognostic significance of microvessel density and other variables in Japanese and British patients with primary invasive breast cancer.

The purpose of this study is to investigate the associations of microvessel density (MVD) and other pathological variables with survival, and whether they accounted for survival differences between Japanese and British patients. One hundred seventy-three Japanese and 184 British patients were included in the study. British patients were significantly older (56.3+/-11.4 years vs 52.5+/-12.9 years; P<0.01) and had smaller tumours (2.2+/-1.3 vs 2.7+/-1.8 cm; P<0.01), which were more frequently oestrogen receptor positive (78.8 vs 57.2%, P<0.01), had more grade III tumours (29.9 vs 21.4%, P=0.04) and more infiltrating lobular carcinomas (13.6 vs 4.0%, P<0.01) and a higher MVD compared with Japanese patients (57.9+/-19.8 vs 53.2+/-18.6; P=0.01). However, no difference in the prevalence of lymph-node metastasis was found between them (39.1 vs 37.5%, P=0.75). Younger British patients (age <50 years) had the highest MVD compared with Japanese and older British patients (P<0.01). Japanese patients were proportionately more likely to receive chemotherapy than endocrine therapy (P<0.01). British patients had a significantly worse relapse-free survival and overall survival compared with Japanese patients, after statistical adjustment for variables (hazard ratio=2.1, 2.4, P<0.01, P<0.01, respectively), especially, in T2 stage, low MVD and older subgroup (HR: 3.6, 5.0; 3.1, 3.3; 3.2, 3.9, respectively), but only in ER negative cases (P=0.04, P=0.01, respectively). The present study shows that MVD contributes to the Japanese-British disparity in breast cancer. However, the MVD variability did not explain the survival differences between Japanese and British patients.

Usefulness of cone beam computed tomography for odontogenic myxoma.

A case of odontogenic myxoma is reported as showing a cyst-like pattern with a partially thick but vague and unclear radiopaque border between the left mandibular second premolar and first molar on rotational panoramic radiography. Internal structure of the lesion displayed radiolucency with a sparse and coarse trabecular pattern. No expansion of bucco-lingual cortical bone was apparent. The radiographic pattern of odontogenic myxoma did not resemble a tennis racket-like or straight, curved and coarse septal appearance on panoramic radiography, but characteristic findings were noted on cone beam CT. Cone beam CT may prove extremely useful in clarifying detailed internal structure and the state of margins.

Exclusive measurement of the nonmesonic weak decay of the lambda(5)He hypernucleus.

We performed a coincidence measurement of two nucleons emitted from the nonmesonic weak decay of lambda(5)He formed via the 6Li(pi+, K+) reaction. The energies of the two nucleons and the pair number distributions in the opening angle between them were measured. In both np and nn pairs, we observed a clean back-to-back correlation coming from the two-body weak reactions of lambda p --> np and lambda n --> nn, respectively. The ratio of the nucleon pair numbers was N(nn)/N(np) = 0.45 +/- 0.11(stat) +/- 0.03(syst) in the kinematic region of cos theta(NN) < -0.8. Since each decay mode was exclusively detected, the measured ratio should be close to the ratio of gamma(lambda p --> np)/gamma(lambda n --> nn). The ratio is consistent with recent theoretical calculations based on the heavy meson and/or direct-quark exchange picture.

A quantitative analysis of lymphatic vessels in human breast cancer, based on LYVE-1 immunoreactivity.

This study was undertaken to determine the highly sensitive method for detecting tumour lymphatic vessels in all the fields of each slide (LV), lymphatic microvessel density (LMVD) and lymphatic vessel invasion (LVI) and to compare them with other prognostic parameters using immunohistochemical staining with polyclonal (PCAB) and monoclonal antibodies (MCAB) to the lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1), and the pan-endothelial marker factor VIII in a series of 67 human breast cancers. In all LYVE-1-stained sections, LV (some of which contained red blood cells) were frequently found localised in extralobular stroma, dermis, connective tissue stroma and adjacent to artery and vein, but were rare within the intralobular stroma or the tumour body (3/67 cases) or areas of widespread invasion. In contrast small blood vessels were observed in intra- and extralobular stroma in the factor VIII-stained sections. Quantitation of vessel numbers revealed that LYVE-1/PCAB detected a significantly larger number of LV than either H&E or LYVE-1/MCAB (P<0.0001). LYVE-1/PCAB detected LVI in 25/67 cases (37.3%) and their presence was significantly associated with both lymph node metastasis (chi(2)=4.698, P=0.0248) and unfavourable overall survival (OS) (P=0.0453), while not relapse- free survival (RFS) (P=0.2948). LMVD had no influence for RFS and OS (P=0.4879, P=0.1463, respectively). Our study demonstrates that immunohistochemistry with LYVE-1/PCAB is a highly sensitive method for detecting tumour LV/LVI in breast cancer and LVI is a useful prognostic indicator for lymphatic tumour dissemination.

Protective effect of diltiazem on hepatic ischemia-reperfusion injury in rats by improving liver tissue blood flow.

BACKGROUND: Cytosolic calcium ions are known to play an important role in ischemia-reperfusion (IR) injury. However, the protective effect of calcium channel blockers remains controversial in liver IR injury. Moreover, calcium channel blockers improve hepatic IR injury not due to blocking an increase in hepatic calcium concentration. Therefore, we hypothesized that calcium antagonists protected a liver from IR injury by a vasodilatory action rather than by the inhibition of an increase in Ca2+ within parenchymal cells. This study evaluated the effects of diltiazem, a calcium channel blocker, on liver energy metabolism and blood flow after IR injury. METHODS: Twenty-seven rats underwent hepatic ischemia for 30 minutes followed by 60 minutes of reperfusion. The animals were allocated into group C (without drug); group D5 (diltiazem, 5 microg/kg per min); or group D10 (diltiazem, 10 microg/kg per min). Diltiazem was infused before laparotomy and then throughout the experiment. RESULTS: After 60 minutes of reperfusion, liver tissue blood flow and ATP concentrations were significantly higher in group D10 than the other animals (both, P < .05). Changes in ATP values strongly correlated those observed in blood flow (R = 0.80, P < .001). CONCLUSION: Diltiazem improved ATP-generating capacity during reperfusion by improving liver tissue blood flow. An improvement in hepatic tissue perfusion may be a therapeutic strategy for liver IR injury.

The combination of angiogenesis and blood vessel invasion as a prognostic indicator in primary breast cancer.

This study was undertaken to examine the interaction between the combination of angiogenesis and blood vessel invasion (BVI) and haematogenous metastasis, and to determine the prognostic significance of that combination in predicting 20-year relapse-free survival (RFS) and overall survival (OS) rates in primary breast cancer. Five hundred and nine patients were studied. We investigated 11 factors, including average microvessel count (AMC)/BVI, lymph-node status (n), clinical tumour size (T), histological grade (HG), lymphatic vessel invasion (LVI), p53, proliferating cell nuclear antigen (PCNA), c-erbB-2, mitotic index (MI), apoptotic index, and tumour necrosis (TN). Blood vessel invasion was detected by both factor VIII-related antigen and elastica van Gieson staining. To evaluate the best objective method to quantify microvessel density in angiogenesis, AMC was employed. The rate of AMC-high and BVI-positive tumours was 32.6 and 29.3%, respectively. That of both AMC-high and BVI-positive tumours was 10.1%. Univariate analysis showed that AMC/BVI, n, T, HG, LVI, p53, PCNA, MI, and TN were significantly predictive of RFS and OS. By multivariate analysis, AMC/BVI was the strongest independent prognostic factor for 20-year RFS (relative risk (RR)=5.5; P<0.0001) and for 20-year OS (RR=4.3; P<0.0001). Lymph-node status was still considered a powerful prognostic indicator; however, the combination of AMC and BVI provided more reliable prognostic information than lymph-node status for haematogenous dissemination.

A nonsurgical technique to create an esophagostomy for difficult cases of percutaneous endoscopic gastrostomy.

BACKGROUND: We developed a minimally invasive technique of esophagostomy called percutaneous transesophageal gastrotubing (PTEG) using a rupture-free balloon (RFB) for enteral nutrition and drainage as well as percutaneous endoscopic gastrostomy (PEG). PTEG using RFB allows surgeons to create a nonsurgical esophagostomy even in difficult cases of PEG (i.e., total gastrectomized patients and massive ascites). METHODS: To create the PTEG, a RFB is inserted into the esophagus through the nose and inflated. The RFB is punctured with a needle at the left neck under ultrasonographic vision. A guidewire is inserted through the needle, followed by dilatation of the punctured site using a dilator with sheath. Finally, the tube is inserted into the gastrointestinal tract and the sheath is peeled off. RESULTS: From January 1998 to June 2002, we treated 115 patients using PTEG with a RFB and there were no major complications. Therapeutic results are as good as those for PEG and it took approximately 15 min to perform. CONCLUSIONS: PTEG with RFB is as safe as PEG and is simple and less invasive. It can be used in some cases for which PEG is contraindicated.

Inhibition of hepatic metastasis in mice treated with cell-binding domain of human fibronectin and angiogenesis inhibitor TNP-470.

BACKGROUND: To prevent tumor metastasis, we administered the cell-binding domain of fibronectin, in combination with the angiogenesis inhibitor TNP-470, to mice with hepatic metastasis. We then assessed the prevention of tumor metastasis resulting from the inhibition of adhesive interactions and the inhibition of angiogenesis. METHODS: A hepatic metastasis model was created by injecting 1 x 10(3) colon 26/TC-1 cells into the anterior mesenteric vein of CDF1 mice. The cell-binding domain obtained from fibronectin included the Arg-Gly-Asp (RGD) sequence. A fibronectin-binding domain (FND)-treated group, an FND plus TNP-470 group, and a control group were established. The animals were killed 4 weeks after the injections of the treatment agents had been completed and the number of metastatic liver nodules was counted. In a simultaneous experiment with the same design, the mice were not killed at 4 weeks, and their survival was observed. RESULTS: The mean number of nodules in the FND plus TNP-470 group was significantly lower than that in the control group (P = 0.019337). The inhibition rate was 51% in the FND group, 60% in the FND 10 micrograms plus TNP-470 10 mg/kg group, and 64% in the FND 10 micrograms plus TNP-470 100 mg/kg group compared with the control group. Mice from the FND group that were not killed died after 6-8 weeks, but mice from the FND plus TNP-470 group died after 8-12 weeks. CONCLUSION: The cell-binding domain of fibronectin may, potentially, be an effective form of antiadhesive therapy that competes with native adhesion molecules and blocks adhesion during the metastatic process. When the cell-binding domain of fibronectin is combined with TNP-470 to inhibit angiogenesis, more effective inhibition of metastatic tumor growth and prolongation of survival can be achieved than after treatment with the cell-binding domain alone.