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Immunohistochemical Analysis of Oral Dysplasia: Diagnostic Assessment by Fascin and Podoplanin Expression

The aim of this study was to investigate fascin and podoplanin expression in oral dysplasia and carcinoma in situ (CIS) immunohistochemically, and to evaluate their relationship to histopathological diagnosis based on architectural and cytological features. Fascin and podoplanin expression patterns were analyzed immunohistologically in 26 specimens of oral lesions, including benign disease (hyperplasia, papilloma, and others), intraepithelial neoplasia/borderline disease (dysplasia), and malignant disease (CIS, invasive squamous cell carcinoma). Fascin expression was scored into four original categories, and podoplanin expression was scored into five previously established categories. The relationship between the immunohistochemically determined scores of fascin and podoplanin expression and the architectural and cytological features in the hematoxylin-eosin-stained slides was analyzed statistically. The immunostaining scores for fascin and podoplanin were significantly higher in dysplasia and CIS than in benign disease (p=0.0011, p=0.00036), and they were significantly higher in dysplasia than in benign disease (p=0.0087, p=0.0032). In all cases of invasive SCC, fascin was expressed mainly in the cytoplasm of the tumor cells and fascin expression extended from the destruction of the basal layer of the epithelium to the upper layer of the epithelium and podoplanin was expressed in the cytoplasm and membrane of the tumor cells. This was the first report of up-regulation of fascin in oral dysplasia. Our results suggest that it would be helpful for improving the diagnostic accuracy of oral dysplasia and CIS to assess the expression of fascin and podoplanin immunohistochemically

Outburst of LS V+44 17 Observed by MAXI and RXTE, and Discovery of a Dip Structure in the Pulse Profile

We report on the first observation of an X-ray outburst of a Be/X-ray binary pulsar LS V +44 17/RX J0440.9+4431, and the discovery of an absorption dip structure in the pulse profile. An outburst of this source was discovered by MAXI GSC in 2010 April. It was the first detection of the transient activity of LS V +44 17 since the source was identified as a Be/X-ray binary in 1997. From the data of the follow-up RXTE observation near the peak of the outburst, we found a narrow dip structure in its pulse profile which was clearer in the lower energy bands. The pulse-phase-averaged energy spectra in the 3$-$100 keV band can be fitted with a continuum model containing a power-law function with an exponential cutoff and a blackbody component, which are modified at low energy by an absorption component. A weak iron K$\alpha$ emission line is also detected in the spectra. From the pulse-phase-resolved spectroscopy we found that the absorption column density at the dip phase was much higher than those in the other phases. The dip was not seen in the subsequent RXTE observations at lower flux levels. These results suggest that the dip in the pulse profile originates from the eclipse of the radiation from the neutron star by the accretion column.Comment: 18 pages, 7 figures, accepted for publication in PAS

Biomarker discovery for practice of precision medicine in hypopharyngeal cancer: a theranostic study on response prediction of the key therapeutic agents

Background: Hypopharyngeal cancer is a relatively rare malignancy with poor prognosis. Current chemotherapeutic algorithm is still far from personalized medicine, and the identification of the truly active therapeutic biomarkers and/or targets is eagerly awaited.Methods: Venturing to focus on the conventional key chemotherapeutic drugs, we identified the most correlative genes (and/or proteins) with cellular sensitivity to docetaxel (TXT), cisplatin (CDDP) and 5-fluorouracil (5-FU) in the expression levels, through 3 steps approach: genome-wide screening, confirmation study on the quantified expression levels, and knock-down and transfection analyses of the candidates. The probable action pathways of selected genes were examined by Ingenuity Pathway Analysis using a large-scale database, The Cancer Genome Atlas.Results: The first genome-wide screening study derived 16 highly correlative genes with cellular drug sensitivity in 15 cell lines (|R| > 0.8, P 0.5, P Conclusion: We newly propose 4 molecules -AGR2, PDE4D,NINJ2 and CDC25B) as the powerful exploratory markers for prediction of cellular response to 3 key chemotherapeutic drugs in hypopharyngeal cancers and also suggest their potentials to be the therapeutic targets, which could contribute to the development of precision medicine of the essential chemotherapy in hypopharyngeal patients.</p

MAXI GSC observations of a spectral state transition in the black hole candidate XTE J1752-223

We present the first results on the black hole candidate XTE J1752-223 from the Gas Slit Camera (GSC) on-board the Monitor of All-sky X-ray Image (MAXI) on the International Space Station. Including the onset of the outburst reported by the Proportional Counter Array on-board the Rossi X-ray Timing Explorer on 2009 October 23, the MAXI/GSC has been monitoring this source approximately 10 times per day with a high sensitivity in the 2-20 keV band. XTE J1752-223 was initially in the low/hard state during the first 3 months. An anti-correlated behavior between the 2-4 keV and 4-20 keV bands were observed around January 20, 2010, indicating that the source exhibited the spectral transition to the high/soft state. A transient radio jet may have been ejected when the source was in the intermediate state where the spectrum was roughly explained by a power-law with a photon index of 2.5-3.0. The unusually long period in the initial low/hard state implies a slow variation in the mass accretion rate, and the dramatic soft X-ray increase may be explained by a sudden appearance of the accretion disk component with a relatively low innermost temperature (0.4-0.7 keV). Such a low temperature might suggest that the maximum accretion rate was just above the critical gas evaporation rate required for the state transition.Comment: Publication of Astronomical Society of Japan Vol.62, No.5 (2010) [in print

Long-term Monitoring of the Black Hole Binary GX 339-4 in the High/Soft State during the 2010 Outburst with MAXI/GSC

We present the results of monitoring the Galactic black hole candidate GX 339-4 with the Monitor of All-sky X-ray Image (MAXI) / Gas Slit Camera (GSC) in the high/soft state during the outburst in 2010. All the spectra throughout the 8-month period are well reproduced with a model consisting of multi-color disk (MCD) emission and its Comptonization component, whose fraction is <= 25% in the total flux. In spite of the flux variability over a factor of 3, the innermost disk radius is constant at R_in = 61 +/- 2 km for the inclination angle of i = 46 deg and the distance of d=8 kpc. This R_in value is consistent with those of the past measurements with Tenma in the high/soft state. Assuming that the disk extends to the innermost stable circular orbit of a non-spinning black hole, we estimate the black hole mass to be M = 6.8 +/- 0.2 M_sun for i = 46 deg and d = 8 kpc, which is consistent with that estimated from the Suzaku observation of the previous low/hard state. Further combined with the mass function, we obtain the mass constraint of 4.3 M_sun < M < 13.3 M_sun for the allowed range of d = 6-15 kpc and i < 60 deg. We also discuss the spin parameter of the black hole in GX 339-4 by applying relativistic accretion disk models to the Swift/XRT data.Comment: 9 pages, 8 figures, accepted for publication in PASJ (Suzaku+MAXI special issue

Bright X-ray flares from the BL Lac object Mrk 421, detected with MAXI in 2010 January and February

Strong X-ray flares from the blazar Mrk 421 were detected in 2010 January and February through the 7 month monitoring with the MAXI GSC. The maximum 2 -- 10 keV flux in the January and February flares was measured as 120 +- 10 mCrab and 164 +- 17 mCrab respectively; the latter is the highest among those reported from the object. A comparison of the MAXI and Swift BAT data suggests a convex X-ray spectrum with an approximated photon index of about 2. This spectrum is consistent with a picture that MAXI is observing near the synchrotron peak frequency. The source exhibited a spectral variation during these flares, slightly different from those in the previous observations, in which the positive correlation between the flux and hardness was widely reported. By equating the halving decay timescale in the January flare, $t_{\rm d} \sim 2.5 \times 10^{4}$ s, to the synchrotron cooling time, the magnetic field was evaluated as B = 0.045 G $(\delta/10)^{-1/3}$, where $\delta$ is the jet beaming factor. Assuming that the light crossing time of the emission region is shorter than the doubling rise time, $t_{\rm r} \lesssim 2 \times 10^{4}$ s, the region size was roughly estimated as $R < 6 \times 10^{15}$ cm $(\delta/10)$. These are consistent with the values previously reported. For the February flare, the rise time, $t_{\rm r} < 1.3 \times 10^{5}$ s, gives a loose upper limit on the size as $R < 4 \times 10^{16}$ cm $(\delta/10)$, although the longer decay time $t_{\rm d} \sim 1.4 \times 10^{5}$ s, indicates B = 0.015 G $(\delta/10)^{-1/3}$, which is weaker than the previous results. This could be reconciled by invoking a scenario that this flare is a superposition of unresolved events with a shorter timescale.Comment: 14 pages, 4 figures, accepted for PASJ (Vol. 62 No. 6

A Spectral Study of the Black Hole Candidate XTE J1752-223 in the High/Soft State with MAXI, Suzaku and Swift

We report on the X-ray spectral analysis of the black hole candidate XTE\ J1752--223 in the 2009--2010 outburst, utilizing data obtained with the MAXI/Gas Slit Camera (GSC), the Swift/XRT, and Suzaku, which work complementarily. As already reported by Nakahira et al. (2010) MAXI monitored the source continuously throughout the entire outburst for about eight months. All the MAXI/GSC energy spectra in the high/soft state lasting for 2 months are well represented by a multi-color disk plus power-law model. The innermost disk temperature changed from $\sim$0.7 keV to $\sim$0.4 keV and the disk flux decreased by an order of magnitude. Nevertheless, the innermost radius is constant at $\sim$41 $D_{3.5}(\cos{\it i})^{-1/2}$ km, where $D_{3.5}$ is the source distance in units of 3.5 kpc and $i$ the inclination. The multi-color disk parameters obtained with the MAXI/GSC are consistent with those with the Swift/XRT and Suzaku. The Suzaku data also suggests a possibility that the disk emission is slightly Comptonized, which could account for broad iron-K features reported previously. Assuming that the obtained innermost radius represents the innermost stable circular orbit for a non-rotating black hole, we estimate the mass of the black hole to be 5.51$\pm$0.28 $M_{\odot}$ $D_{3.5}(\cos{\it i})^{-1/2}$, where the correction for the stress-free inner boundary condition and color hardening factor of 1.7 are taken into account. If the inclination is less than 49$^{\circ}$ as suggested from the radio monitoring of transient jets and the soft-to-hard transition in 2010 April occurred at 1--4% of Eddignton luminosity, the fitting of the Suzaku spectra with a relativistic accretion-disk model derives constraints on the mass and the distance to be 3.1--55 $M_{\odot}$ and 2.3--22 {\rm kpc}, respectively. This confirms that the compact object in XTE J1752--223 is a black hole.Comment: 12 pages including 7 figures and 4 tables, accepted for publication in PAS