Radiosensitization by telomerase-dependent oncolytic adenovirus

DNA修復機能阻害は放射線感受性を増強させるため，DNA修復に関与する因子の阻害剤は放射線増感剤となり得る．我々の開発したテロメラーゼ依存的腫瘍融解アデノウイルス製剤OBP-301（テロメライシン）は，アデノウイルスE1B55kDaタンパクを介して細胞のDNA修復に重要な役割を果たすMRN複合体（Mre11，Rad50，NBS1）を分解する機能を有する．このMRN複合体の分解によりATM（ataxia-telangiectasia mutated）の活性化が抑制され結果的にDNA修復機構が阻害される．我々はOBP-301と放射線との併用が強力な相乗効果を生み出すことをマウスの皮下腫瘍モデルおよび食道癌同所性モデルにおいて証明した．これらの結果はOBP-301が将来有望な放射線増感剤となり得ることだけでなく，E1B55kDaタンパクを産生する腫瘍融解アデノウイルス製剤と放射線との併用が悪性腫瘍に対する有力な治療戦略となり得ることを示す

Cooperative Effect of Coulomb Interaction and Electron-Phonon Coupling on the Heavy Fermion State in the Two-Orbital Periodic Anderson Model

We investigate the two-orbital periodic Anderson model, where the local orbital fluctuations of f-electrons couple with a two-fold degenerate Jahn-Teller phonon, by using the dynamical mean-field theory. It is found that the heavy fermion state caused by the Coulomb interaction between f-electrons U is largely enhanced due to the electron-phonon coupling g, in contrast to the case with the single-orbital periodic Anderson model where the effects of U and g compete to each other. In the heavy fermion state for large $U$ and g, both the orbital and lattice fluctuations are enhanced, while the charge (valence) and spin fluctuations are suppressed. In the strong coupling regime, a sharp soft phonon mode with a large spectral weight is observed for small U, while a broad soft phonon mode with a small spectral weight is observed for large U. The cooperative effect of U and g for half-filling with two f-electrons per atom $n_f=2$ is more pronounced than that for quarter-filling with $n_f=1$.Comment: 8 pages, 11 figures, accepted for publication in JPS

Preliminary Characterization of Extracellular Allelochemicals of the Toxic Marine Dinoflagellate Alexandrium tamarense Using a Rhodomonas salina Bioassay

Members of the marine dinoflagellate genus Alexandrium are known to exude allelochemicals, unrelated to well-known neurotoxins (PSP-toxins, spirolides), with negative effects on other phytoplankton and marine grazers. Physico/chemical characterization of extracellular lytic compounds of A. tamarense, quantified by Rhodomonas salina bioassay, showed that the lytic activity, and hence presumably the compounds were stable over wide ranges of temperatures and pH and were refractory to bacterial degradation. Two distinct lytic fractions were collected by reversed-phase solid-phase extraction. The more hydrophilic fraction accounted for about 2% of the whole lytic activity of the A. tamarense culture supernatant, while the less hydrophilic one accounted for about 98% of activity. Although temporal stability of the compounds is high, substantial losses were evident during purification. Lytic activity was best removed from aqueous phase with chloroform-methanol (3:1). A “pseudo-loss” of lytic activity in undisturbed and low-concentrated samples and high activity of an emulsion between aqueous and n-hexane phase after liquid-liquid partition are strong evidence for the presence of amphipathic compounds. Lytic activity in the early fraction of gel permeation chromatography and lack of activity after 5 kD ultrafiltration indicate that the lytic agents form large aggregates or macromolecular complexes

Assessment of two 3D MDCT colonography protocols for observation of colorectal polyps

OBJECTIVE. The objective of our study was to assess the value of two-way interpretation (i.e., from rectum to cecum and vice versa) compared with one-way interpretation (i.e., from rectum to cecum only) in terms of polyp detection and interpretation time on MDCT colonography. MATERIALS AND METHODS. Fifty consecutive patients underwent both CT colonography and conventional colonoscopy. Three radiologists independently analyzed the CT colonographic examinations of each patient using a primary 3D method. All examinations were analyzed using two techniques: navigation from rectum to cecum only (one-way) and navigation from rectum to cecum and vice versa (two-way). Sensitivity and positive predictive value were calculated on both a per-polyp basis and a per-patient basis. Alternative free-response receiver operating characteristic (ROC) curve analysis was estimated, and image interpretation time was documented. RESULTS. One hundred fifty-five polyps were depicted in 45 patients by colonoscopy. The mean sensitivity of CT colonography for polyp detection with two-way (88.4%) was significantly superior to that with one-way (78.1%) (p < 0.01). The mean positive predictive value of each observer with one-way was 66.7%, whereas that with two-way was 65.8%. The mean area under the alternative free-response ROC curve (A z value) with two-way (0.827) was higher than that with one-way (0.816), but there was not a statistically significant difference. The average interpretation time of each observer with two-way (39 min) was statistically significantly longer than that with one-way (25 min) (p < 0.01). CONCLUSION. When using a primary 3D interpretation technique at CT colonography, complete 3D navigation from rectum to cecum and from cecum to rectum is mandatory to maximize polyp detection. The image interpretation time for two-way interpretation is statistically significantly longer than that with one-way interpretation. © American Roentgen Ray Society