Immunohistochemical Analysis of Neuroendocrine (NE) Differentiation in Testicular Germ Cell Tumors (GCTs): Use of Confocal Laser Scanning Microscopy (CLSM) to Demonstrate Direct NE Differentiation from GCTs

Neuroendocrine (NE) differentiation is infrequent in testicular tumors and its histogenesis is not well understood. The present study is aimed at elucidating the pathway of neuroendocrine differentiation in germ cell tumors (GCTs) of the testis. In the analysis of 46 germ cell tumor components from 23 testicular tumors, we focused on GCTs with neuroendocrine differentiation, 7 teratoma, 1 embryonal carcinoma and 1 neuroendocrine carcinoma by immunohistochemical study and confocal laser scanning microscopy (CLSM) analysis. NE marker positive cells were noted in the tumor with collision of teratoma and embryonal carcinoma (E&T tumor), in the immature columnar cells of transitional form of embryonal carcinoma to teratoma (E-T cells) and neuroendocrine carcinoma cells, in addition to the well known mature intestinal mucosa in teratoma. Double staining for a NE marker (CGA) and a germ cell marker (PLAP) demonstrated the localization of both proteins in the same E-T cells confirmed by CLSM. Another finding, indicating the intimate relation between embryonal carcinoma and neuroendcrine differentiation, is that neuroendocrine carcinoma expressed a marker of embryonal carcinoma, CD30. The present results indicated that the NE cells might be differentiated from embryonal carcinoma, a view that has not been proposed before, but that is made in the present study using CLSM

Smoking cessation is associated with increased plasma adiponectin levels in men

SummaryObjectivesLow levels of adiponectin, an adipocytokine with anti-diabetic and anti-atherogenic properties, are associated with increased risk of future myocardial infarction in men. Previous studies have demonstrated that cigarette smoking is involved in the development of insulin resistance, and current smokers have been shown to have reduced plasma adiponectin levels. However, the influence of smoking cessation on adiponectin levels remains unknown. We sought to assess whether smoking cessation is associated with increased plasma adiponectin levels in men.MethodsThe study includes 72 men (47 non-smokers and 25 current smokers at baseline) with stable angina pectoris who underwent percutaneous coronary intervention and follow-up coronary angiography 6 months later. During the 6-month follow-up period, all 47 non-smokers remained non-smokers, while 15 men of the 25 baseline current smokers successfully quit smoking. We evaluated plasma adiponectin levels at coronary intervention and 6 months later.ResultsPlasma adiponectin levels at coronary intervention were comparable to those after 6 months in non-smokers (4.22 [3.15–6.43] vs. 4.58 [3.03–6.26]μg/mL, P=0.124) and in persistent smokers (4.77 [4.25–10.53] vs. 5.16 [4.11–8.10]μg/mL, P=0.721). Meanwhile, an increase in adiponectin level was observed in patients who quit smoking for 6 months (4.24 [3.30–5.70] vs. 5.50 [4.03–8.00]μg/mL, P=0.002). Univariate analysis revealed that the percent increase in adiponectin levels correlated positively with smoking cessation (P=0.003) and negatively with additional use of β-blockers (P=0.049). In addition, increases in adiponectin levels were closely associated with increase in high-density lipoprotein cholesterol (P=0.148), decrease in triglycerides (P=0.140), and additional use of renin–angiotensin system inhibitors (P=0.069). Multivariate analysis demonstrated that smoking cessation was an independent determinant of the increase in adiponectin (P=0.036).ConclusionsSmoking cessation is associated with increased plasma adiponectin levels in men with stable angina, suggesting that the significance of smoking cessation may be partly explained by the increase in adiponectin level

HER2 testing on core needle biopsy specimens from primary breast cancers: interobserver reproducibility and concordance with surgically resected specimens

<p>Abstract</p> <p>Background</p> <p>Accurate evaluation of human epidermal growth factor receptor type-2 (HER2) status based on core needle biopsy (CNB) specimens is mandatory for identification of patients with primary breast cancer who will benefit from primary systemic therapy with trastuzumab. The aim of the present study was to validate the application of HER2 testing with CNB specimens from primary breast cancers in terms of interobserver reproducibility and comparison with surgically resected specimens.</p> <p>Methods</p> <p>A total of 100 pairs of archival formalin-fixed paraffin-embedded CNB and surgically resected specimens of invasive breast carcinomas were cut into sections. All 100 paired sections were subjected to HER2 testing by immunohistochemistry (IHC) and 27 paired sections were subjected to that by fluorescence in situ hybridization (FISH), the results being evaluated by three and two observers, respectively. Interobserver agreement levels in terms of judgment and the concordance of consensus scores between CNB samples and the corresponding surgically resected specimens were estimated as the percentage agreement and κ statistic.</p> <p>Results</p> <p>In CNB specimens, the percentage interobserver agreement of HER2 scoring by IHC was 76% (κ = 0.71) for 3 × 3 categories (0-1+ <it>versus </it>2+ <it>versus </it>3+) and 90% (κ = 0.80) for 2 × 2 categories (0-2+ <it>versus </it>3+). These levels were close to the corresponding ones for the surgically resected specimens: 80% (κ = 0.77) for 3 × 3 categories and 92% (κ = 0.88) for 2 × 2 categories. Concordance of consensus for HER2 scores determined by IHC between CNB and the corresponding surgical specimens was 87% (κ = 0.77) for 3 × 3 categories, and 94% (κ = 0.83) for 2 × 2 categories. Among the 13 tumors showing discordance in the mean IHC scores between the CNB and surgical specimens, the results of consensus for FISH results were concordant in 11. The rate of successful FISH analysis and the FISH positivity rate in cases with a HER2 IHC score of 2+ differed among specimens processed at different institutions.</p> <p>Conclusion</p> <p>It is mandatory to study HER2 on breast cancers, and either CNB or surgical specimen can be used.</p

A Search for Lyman alpha Emitters at Redshift 3.7

We present the results of a survey for emission-line objects based on optical intermediate-band ($\lambda_{\rm c}$ = 5736 \AA ~ and $\Delta\lambda$ = 280 \AA) and broad-band ($B$, $V$, $R$, and $i^\prime$) observations of the Subaru/XMM-Newton Deep Field on the 8.2 m Subaru telescope with the Subaru Prime Focus Camera, Suprime-Cam. All the data were obtained during the guaranteed time observations of the Suprime-Cam instrument. The intermediate-band image covered a sky area with 10\minpoint62 \times 12\minpoint40 \approx 132 arcmin$^2$ in the Subaru/XMM-Newton Deep Field (Ouchi et al.). Using this image, we have found 23 emission-line sources whose observed emission-line equivalent widths are greater than 250 \AA. Their optical multicolor properties indicate that six emission-line sources are Ly$\alpha$ emitters at $z \approx$ 3.7 ($\Delta z \approx 0.22$). They are either intense starburst galaxies or active galactic nuclei like quasars at $z \approx$ 3.7. Two more emission-line sources may also be Ly$\alpha$ emitters at $z \approx$ 3.7 although their multicolor properties are marginal. Among the remaining 15 emission-line objects, eight objects appear strong emission-line galaxies at lower redshift; e.g., [O {\sc ii}] $\lambda$3727 emitters at $z \approx 0.54$, H$\beta$ at $z \approx 0.18$, or [O {\sc iii}]$\lambda$5007 emitters at $z \approx 0.15$. The remaining seven objects are unclassified because they are too faint to be detected in broad-band images. We discuss observational properties of these strong emission-line sources. In particular, our data allow us to estimate the star formation density at $z \approx 3.7$ for the first time.Comment: Accepted for publication in AJ;14 pages, 26 figures (all figures are JPEG file

EMPRESS. XII. Statistics on the Dynamics and Gas Mass Fraction of Extremely-Metal Poor Galaxies

We present demography of the dynamics and gas-mass fraction of 33 extremely metal-poor galaxies (EMPGs) with metallicities of $0.015-0.195~Z_\odot$ and low stellar masses of $10^4-10^8~M_\odot$ in the local universe. We conduct deep optical integral-field spectroscopy (IFS) for the low-mass EMPGs with the medium high resolution ($R=7500$) grism of the 8m-Subaru FOCAS IFU instrument by the EMPRESS 3D survey, and investigate H$\alpha$ emission of the EMPGs. Exploiting the resolution high enough for the low-mass galaxies, we derive gas dynamics with the H$\alpha$ lines by the fitting of 3-dimensional disk models. We obtain an average maximum rotation velocity ($v_\mathrm{rot}$) of $15\pm3~\mathrm{km~s^{-1}}$ and an average intrinsic velocity dispersion ($\sigma_0$) of $27\pm10~\mathrm{km~s^{-1}}$ for 15 spatially resolved EMPGs out of the 33 EMPGs, and find that all of the 15 EMPGs have $v_\mathrm{rot}/\sigma_0<1$ suggesting dispersion dominated systems. There is a clear decreasing trend of $v_\mathrm{rot}/\sigma_0$ with the decreasing stellar mass and metallicity. We derive the gas mass fraction ($f_\mathrm{gas}$) for all of the 33 EMPGs, and find no clear dependence on stellar mass and metallicity. These $v_\mathrm{rot}/\sigma_0$ and $f_\mathrm{gas}$ trends should be compared with young high-$z$ galaxies observed by the forthcoming JWST IFS programs to understand the physical origins of the EMPGs in the local universe.Comment: 18 pages, 9 figures, accepted for publication in Ap

EMPRESS. IX. Extremely Metal-Poor Galaxies are Very Gas-Rich Dispersion-Dominated Systems: Will JWST Witness Gaseous Turbulent High-z Primordial Galaxies?

We present kinematics of 6 local extremely metal-poor galaxies (EMPGs) with low metallicities ($0.016-0.098\ Z_{\odot}$) and low stellar masses ($10^{4.7}-10^{7.6} M_{\odot}$). Taking deep medium-high resolution ($R\sim7500$) integral-field spectra with 8.2-m Subaru, we resolve the small inner velocity gradients and dispersions of the EMPGs with H$\alpha$ emission. Carefully masking out sub-structures originated by inflow and/or outflow, we fit 3-dimensional disk models to the observed H$\alpha$ flux, velocity, and velocity-dispersion maps. All the EMPGs show rotational velocities ($v_{\rm rot}$) of 5--23 km s$^{-1}$ smaller than the velocity dispersions ($\sigma_{0}$) of 17--31 km s$^{-1}$, indicating dispersion-dominated ($v_{\rm rot}/\sigma_{0}=0.29-0.80<1$) systems affected by inflow and/or outflow. Except for two EMPGs with large uncertainties, we find that the EMPGs have very large gas-mass fractions of $f_{\rm gas}\simeq 0.9-1.0$. Comparing our results with other H$\alpha$ kinematics studies, we find that $v_{\rm rot}/\sigma_{0}$ decreases and $f_{\rm gas}$ increases with decreasing metallicity, decreasing stellar mass, and increasing specific star-formation rate. We also find that simulated high-$z$ ($z\sim 7$) forming galaxies have gas fractions and dynamics similar to the observed EMPGs. Our EMPG observations and the simulations suggest that primordial galaxies are gas-rich dispersion-dominated systems, which would be identified by the forthcoming James Webb Space Telescope (JWST) observations at $z\sim 7$.Comment: Submitted to ApJ; After revisio

Somatostatin analogue inhibits mobility of prostate carcinoma cells and SSTR2a is a prognostic and therapeutic biomarker for prostate carcinoma

The somatostatin analogue (SA), Octreotide, has been used as a therapeutic reagent for somatostatin receptor type 2a (SSTR2a)-positive cancers. The purpose of this study is to detect SSTR2a in human prostate carcinomas and to elucidate the effects of SA on SSTR2a-positive prostate carcinoma cells to determine the potential of this drug as a new therapeutic method for advanced prostate carcinoma. Material and Methods: Immunohistochemical study of SSTR2a was performed on 108 prostate carcinoma cases. RT-PCR analysis was performed on 11 needle biopsy and 3 metastatic cases. Proliferation, migration and invasion assays were performed by using SSTR2a-positive prostate cancer cells, DU145 and PC3, treated with SA and/or Rho-kinase inhibitor Y-27632. Morphological changes of prostate carcinoma cells were also examined by staining for vinculin, rhodamine phalloidin, and alpha tubulin. Results: The study showed expression of SSTR2a in 13 of the 108 cases (12%); the histological grade (Gleason) and tumor stage of the prostate carcinoma were directly related to SSTR2a expression. Among the seven cases of lymph node (LN) metastasis, SSTR2a expression was markedly higher. SSTR2 mRNA was detected by RT-PCR in only 4 of 11 needle biopsy cases and 1 of 3 cases of LN metastasis. Migration and invasion abilities of DU145 and PC3 cells were inhibited by SA in a dose-dependent manner. This inhibition was reversed by Y-27632. Morphological changes of the prostate cancer cells treated with SA and Y27632 corroborate the migration and invasion assays, although SA had no effect on proliferation of DU145 and PC3 cells. Conclusion: SSTR2a is a potential prognostic factor for prostatic carcinoma. SA may be beneficial for patients with advanced prostate carcinoma or to protect from distal metastasis if they are positive for SSTR2a