P53, hTERT, WT-1, and VEGFR2 are the most suitable targets for cancer vaccine therapy in HLA-A24 positive pancreatic adenocarcinoma

13301甲第4088号博士（医学）金沢大学博士論文本文Full 以下に掲載：Cancer Immunology Immunotherapy 63(5) pp.479-489 2014. Springer Verlag. 共著者：Takeshi Terashima, Eishiro Mizukoshi, Kuniaki Arai, Tatsuya Yamashita, Mariko Yoshida, Hajime Ota, Ichiro Onishi, Masato Kayahara, Koushiro Ohtsubo, Takashi Kagaya, Masao Honda, Shuichi Kanek

Roles of histone methyl-modifying enzymes in development and progression of cancer

がん進展制御研究所Retroviral insertional mutagenesis in mice is considered a powerful forward genetic strategy to identify disease genes involved in cancer. Our high-throughput screens led to frequent identification of the genes encoding the enzymes engaged in histone lysine methylation. Histone methylation can positively or negatively impact on gene transcription, and then fulfill important roles in developmental control and cell-fate decisions. A tremendous amount of progress has accelerated the characterization of histone methylations and the enzymes that regulate them. Deregulation of these histone methyl-modifying enzymes has been increasingly recognized as a hallmark of cancer in the last few years. However, in most cases, we have only limited understanding for the molecular mechanisms by which these enzymes contribute to cancer development and progression. In this review, we summarize the current knowledge regarding some of the best-validated examples of histone lysine methyltransferases and demethylases associated with oncogenesis and discuss their potential mechanisms of action. © 2013 Japanese Cancer Association

Precision Fe Kalpha and Fe Kbeta Line Spectroscopy of the Seyfert 1.9 Galaxy NGC 2992 with Suzaku

We present detailed time-averaged X-ray spectroscopy in the 0.5--10 keV band of the Seyfert~1.9 galaxy NGC 2992 with the Suzaku X-ray Imaging Spectrometers (XIS). We model the complex continuum in detail. There is an Fe K line emission complex that we model with broad and narrow lines and we show that the intensities of the two components are decoupled at a confidence level >3sigma. The broad Fe K line has an EW of 118 (+32,-61) eV and could originate in an accretion disk (with inclination angle greater than ~30 degrees). The narrow Fe Kalpha line has an EW of 163 (+47,-26) eV and is unresolved FWHM <4090 km/s) and likely originates in distant matter. The absolute flux in the narrow line implies that the column density out of the line-of-sight could be much higher than measured in the line-of-sight, and that the mean (historically-averaged) continuum luminosity responsible for forming the line could be a factor of several higher than that measured from the data. We also detect the narrow Fe Kbeta line with a high signal-to-noise ratio and describe a new robust method to constrain the ionization state of Fe responsible for the Fe Kalpha and Fe Kbeta lines that does not require any knowledge of possible gravitational and Doppler energy shifts affecting the line energies. For the distant line-emitting matter (e.g. the putative obscuring torus) we deduce that the predominant ionization state is lower than Fe VIII (at 99% confidence), conservatively taking into account residual calibration uncertainties in the XIS energy scale and theoretical and experimental uncertainties in the Fe K fluorescent line energies. From the limits on a possible Compton-reflection continuum it is likely that the narrow Fe Kalpha and Fe Kbeta lines originate in a Compton-thin structure.Comment: Abstract is abridged. Accepted for publication in the Suzaku special issue of PASJ (November 2006). 18 pages, 6 figure

A Case of Radiation Fibrosis Appearing as Mass-Like Consolidation after SBRT with Elevation of Serum CEA

We report a case of radiation fibrosis appearing as mass-like consolidation, which was difficult to distinguish from local recurrence. A 72-year-old woman was diagnosed as having primary lung cancer (cT1N0M0 stage IA) in the right upper lobe and was treated with SBRT of 48 Gy in 4 fractions. After 12 months, mass-like consolidation appeared around the irradiated area, and after 13 months, it had increased in size. FDG-PET revealed high uptake (SUV max = 5.61) for the consolidation. CT-guided biopsy was performed, but we could not confirm the diagnosis. Considering her poor respiratory function and her age, short-interval follow-up was performed. After 15 months, the consolidation enlarged at the dorsal side, and carcinoembryonic antigen (CEA) became elevated (14.6 ng/mL). Serum KL-6 (436 U/mL) and SP-D (204 ng/mL) were also elevated. However, after 16 months, serum CEA slightly decreased. The consolidation gradually retracted on follow-up CT images. CEA, KL-6, and SP-D were also decreased by degrees. After 40 months, there is no evidence of local recurrence

ヘイセイ 27ネンド ゼンコク ガクリョク ガクシュウ ジョウキョウ チョウサ ノ モンダイ オ モチイタ キョウイン シボウ ダイガクセイ ノ リカ ノ ガクリョク チョウサ

We carried out an academic survey in science for 80 undergraduates of teacher training courses using 25 science problems of the national school achievement tests conducted in 2015 for 9th grade students at lower secondary school in Japan. Based on the results, we found the following trends in their academic abilities : Although the total average correctness of the undergraduates is about 75％，the itemized scores for physics, chemistry, biology and earth science are significantly different each other. The undergraduates are good at chemistry and biology, whereas they are poor at earth science and physics. The difference in achievement for the undergraduates between the four scientific content domains can be originated from their major subjects at upper secondary school. From the correlation in the correctness for each problem between the undergraduates and 9th graders, both of them are found to share some common weaknesses. Moreover, we found some strong and weak points peculiar to the pre−service teachers

モザンビーク キョウワコク ノ ショウガッコウ リカ ノ ガクシュウ ナイヨウ ノ トクチョウ

We analyzed the scientific leaning contents at primary education in Mozambique, comparing to Japanese primary science education. We categorized the learning units about science in the curriculum guideline for Mozambique\u27s primary education in 2017 into seven content domains, "scientific methodology", "physics (energy)", "chemistry (substance/particle)", "biology (life)", "earth science (earth)", "technology and industry" and "healthy and safety life" according to their learning topics. We also tabulated the number of class hours allocated to each unit. As a result, the class hours for teaching "healthy and safety life" with "technology and industry" are found to account for about two third of all class hours, while learning topics about "physics (energy)", "chemistry (substance/particle)" and "earth science (earth)" of Mozambique are quite less than those of Japan. The present primary science curriculum of Mozambique is found to be biased qualitatively and quantitatively towards teaching knowledge necessary for daily life rather than learning correct scientific concepts

Wide-band spectroscopy of the Compton thick Seyfert 2 galaxy Mrk 3 with Suzaku

We obtained a wide-band spectrum of the Compton-thick Seyfert 2 galaxy Mrk 3 with Suzaku. The observed spectrum was clearly resolved into weak, soft power-law emission, a heavily absorbed power-law component, cold reflection, and many emission lines. The heavily absorbed component, absorbed by gas with a column density of 1.1x10^24 cm^-2, has an intrinsic 2--10 keV luminosity of ~1.6x10^43 erg s^-1, and is considered to be direct emission from the Mrk 3 nucleus. The reflection component was interpreted as reflection of the direct light off cold, thick material; the reflection fraction $R$ was 1.36+/-0.20. The cold material is inferred to be located > 1 pc from the central black hole of Mrk 3 due to the low ionization parameter of iron (xi < 1 erg cm s^-1) and the narrow iron line width (s < 22 eV). A Compton shoulder to the iron line was detected, but the intensity of the shoulder component was less than that expected from spherically distributed Compton-thick material. The weak, soft power-law emission is considered to be scattered light by ionized gas. The existence of many highly-ionized lines from O, Ne, Mg, Si, S, and Fe in the observed spectrum indicates that the ionized gas has a broad ionized structure, with xi=10--1000. The scattering fraction with respect to the direct light was estimated to be 0.9+/-0.2%, which indicates that the column density of the scattering region is about 3.6x10^22 cm^-2. This high-quality spectrum obtained by Suzaku can be considered a template for studies of Seyfert 2 galaxies.Comment: 24 pages, 8 figures, accepted in PASJ for publicatio

Jmjd5, an H3K36me2 histone demethylase, modulates embryonic cell proliferation through the regulation of Cdkn1a expression.

Covalent modifications of histones play an important role in chromatin architecture and dynamics. In particular, histone lysine methylation is important for transcriptional control during diverse biological processes. The nuclear protein Jmjd5 (also called Kdm8) is a histone lysine demethylase that contains a JmjC domain in the C-terminal region. In this study, we have generated Jmjd5-deficient mice (Jmjd5Δ/Δ) to investigate the in vivo function of Jmjd5. Jmjd5Δ/Δ embryos showed severe growth retardation, resulting in embryonic lethality at the mid-gestation stage. Mouse embryonic fibroblasts (MEFs) derived from Jmjd5 hypomorphic embryos (Jmjd5neo/neo) also showed the growth defect. Quantitative PCR analysis of various cell cycle regulators indicated that only Cdkn1a expression was upregulated in Jmjd5neo/neo MEFs and Jmjd5Δ/Δ embryos. A knockdown assay with Cdkn1a-specific small interfering RNAs revealed that the growth defect of Jmjd5neo/neo MEFs was significantly rescued. In addition, a genetic study using Jmjd5Δ/Δ; Cdkn1aΔ/Δ double-knockout mice showed that the growth retardation of Jmjd5Δ/Δ embryos was partially rescued by Cdkn1a deficiency. Chromatin immunoprecipitation analysis showed that increased di-methylated lysine 36 of histone H3 (H3K36me2) and reduced recruitment of endogenous Jmjd5 were detected in the transcribed regions of Cdkn1a in Jmjd5neo/neo MEFs. Taken together, these results suggest that Jmjd5 physiologically moderates embryonic cell proliferation through the epigenetic control of Cdkn1a expression.Accepted December 16, 2011

Non-planar Diagrams and Non-commutative Superspace in Dijkgraaf-Vafa theory

We consider the field theory on non-commutative superspace and non-commutative spacetime that arises on D-branes in Type II superstring theory with a constant self-dual graviphoton and NS-NS $B$ field background. $\N=1$ supersymmetric field theories on this non-commutative space (such theories are called $\N=1/2$ supersymmetric theories.) can be reduced to supermatrix models as in hep-th/0303210 \cite{KKM}. We take an appropriate commutative limit in these theories and show that holomorphic quantities in commutative field theories are equivalent to reduced models, including non-planar diagrams to which the graviphoton contributes. This is a new derivation of Dijkgraaf-Vafa theory including non-planar diagrams.Comment: 15 pages, 1 figure, the version to appear in Phys. Lett.