TUMOR MARKERS IN BONE MARROW IN PATIENTS WITH PROSTATIC CANCER

We compared prostatic specific acid phosphatase (PAP), prostatic specific antigen (PA) and γ-seminoprotein (γ-SM) levels between bone marrow and serum for the purpose of assessing of the usefulness of these tumor markers in early detection of bone metastasis in cases with prostatic cancer. Thirty-three patients were entered into this study. Of the patients, 20 had prostatic cancer including 11 with bone metastasis, and 13 patients had benign prostatic hypertrophy (BPH) served as controls. It seemed unlikely that bone marrow PAP, PA and γ-SM are more useful than their serum levels for detection of bone metastasis of prostatic cancer. Because correlation between bone marrow and serum levels of each marker was observed not only in cases with prostate cancer accompanied by bone metastasis but also in metastasis-free prostatic cancer and BPH cases, it seems likely that PAP, PA and γ-SM in bone marrow circulate from peripheral blood rather than from bone metastasis of prostatic cancer

Preparation and crystal structure of [enH(2)](0.5)[Ho(HPO4)(SO4)(H2O)] (en; ethylenediamine)

Single crystals of an organically templated holmium hydrogen phosphate sulfate, [enH(2)](0.5)[Ho(HPO4)(SO4)(H2O)] (en; ethylenediamine) were prepared by hydrothermal reaction and its crystal structure was determined by single crystal X-ray diffraction data. This compound crystallized in the monoclinic system, space group P2(1)/a (No. 14) and the unit cell parameters are a 12.938(5), b = 6.834(3), c = 9.100(2) angstrom, and beta=88.12(2)degrees. The crystal structure is similar to that of [enH(2)](0.5)[Ce(HPO4)(SO4)(H2O)] which had a layered structure built tip by Cc centered polyhedra and HPO4 and SO4 tetrahedra, and the diprotonated ethylenediamine cations were located in the interlayer. For other rare earth elements two types of compounds were obtained tinder hydrothermal conditions. The compounds of R = La, Pr, Nd, Sm and Eu are isostructural with [enH(2)](0.5)[Ce(HPO4)(SO4)(H2O)] and those of Gd, Th, Dy, Er and Yb with [enH(2)](0.5)[Ho(HPO4)(SO4)(H2O)]. The unit cell volumes of these compounds decrease by lanthanide contraction. The compounds of R except La, Sm and Eu exhibited the Curie-Weiss paramagnetic behavior. (C)2010 The Ceramic Society of Japan. All rights reserved

バネ デ ケツゴウ サレタ シンドウコケイ ノ ドウキ セイギョ ノ カイセキ

同一のプロセスが繰り返されるリズム現象は、振り子の振動や化学反応、あるいは生物の体内時計のように数多く知られている。特に非線形振動子同士がある種の相互作用を持つ時、同期して振動する現象は「引き込み」と呼ばれ、数理的な研究が盛んに行われている。生物の体内時計が太陽の運動に同期して概日性リズムを生じて生命活動に役立てていることや、神経振動子群のモデルを用いることで柔軟な歩行運動を生成できる可能性が指摘されるなど、同期現象は基礎的な興味に留まらず種々の応用が期待されている。制御理論の立場からもFradkov［1,2］らは振動子の同期をエネルギ制御によって実現できることを指摘している。この手法は十分に小さな制御入力によって制御目的を達成し、系の特徴を利用した有用な方法である。しかしながら、Fradkovらの研究では振動子の同期の機序について十分に考察されていることは言い難い。そこで本研究では位相モデル［3］を用いて系を縮約し、制御系の同期について詳細を明らかにする

Anti-Cancer Effects of REIC/Dkk-3-encoding Adenoviral Vector for the Treatment of Non-small Cell Lung Cancer

<div><p>Objectives</p><p>REIC/Dkk-3 is down-regulated in a broad range of human cancer cells and is considered to function as a tumor suppressor. We previously reported that REIC/Dkk-3-expressing adenovirus vector (Ad-REIC) induced endoplasmic reticulum (ER) stress and cancer-specific apoptosis in human prostate cancer. In this study, we examined the therapeutic impact of Ad-REIC on non-small cell lung cancer (NSCLC).</p><p>Materials and Methods</p><p>We examined the anti-tumor effect of Ad-REIC on 25 NSCLC cell lines <i>in vitro</i> and A549 cells <i>in vivo</i>. Two of these cell lines were artificially established as EGFR-tyrosine kinase inhibitor (TKI) resistant sublines.</p><p>Results</p><p>Ad-REIC-treatment inhibited the cell viability by 40% or more in 13 (52%) of the 25 cell lines at multiplicity of infection (MOI) of 20 (20 MOI). These cell lines were regarded as being highly sensitive cells. The cell viability of a non-malignant immortalized cell line, OUMS-24, was not inhibited at 200 MOI of Ad-REIC. The effects of Ad-REIC on EGFR-TKI resistant sublines were equivalent to those in the parental cell lines. Here, we demonstrated that Ad-REIC treatment activated c-Jun N-terminal kinase (JNK) in NSCLC cell lines, indicating the induction of ER stress with GRP78/BiP (GRP78) up-regulation and resulting in apoptosis. A single intratumoral injection of Ad-REIC significantly inhibited the tumorigenic growth of A549 cells <i>in vivo</i>. As predictive factors of sensitivity for Ad-REIC treatment in NSCLC, we examined the expression status of GRP78 and coxsackievirus and adenovirus receptor (CAR). We found that the combination of the GRP78 and CAR expressional statuses may be used as a predictive factor for Ad-REIC sensitivity in NSCLC cells.</p><p>Conclusion</p><p>Ad-REIC induced JNK activation and subsequent apoptosis in NSCLC cells. Our study indicated that Ad-REIC has therapeutic potential against NSCLC and that the expression statuses of GRP78 and CAR may predict a potential therapeutic benefit of Ad-REIC.</p></div

Anti-tumor effect of Ad-REIC treatment on A549 tumor growth <i>in vivo</i>.

<p>(a) The mean volume of the subcutaneous xenograft tumors was calculated for 5 mice in each group. A significant difference was observed between the results of Ad-REIC and Ad-LacZ treatment (*p<0.001 by repeated measurement of ANOVA). (b) Appearance of the tumors at the time of sacrifice after treatment with PBS, Ad-LacZ, and Ad-REIC.</p

Ad-REIC sensitivity and categories based on predictive factors.

<p>Ad-REIC sensitivity and categories based on predictive factors.</p

Sensitivity and predictive factors of sensitivity for Ad-REIC treatment in 25 NSCLC cell lines.

<p>The inhibition rates of 25 NSCLC cell lines transfected with Ad-REIC compared to Ad-LacZ are shown as black bar in 20 MOI and white bar in 200 MOI. Thirteen cell lines with over 40% inhibition rate in 20 MOI are defined as highly sensitive and 12 cell lines with lower inhibition rate in 20 MOI are defined as resistant. All the resistant cell lines shows over 40% inhibition rate in 200 MOI. The cell lines are classified into 3 categories based on the GRP and CAR protein expression level as follows; category A (low GRP/high CAR), category B (low GRP/low CAR or high GRP/high CAR), category C (high GRP/low CAR). All 8 highly sensitive cell lines were included in category A, and all 5 resistant cell lines were included in category C. Sq; squamous cell carcinoma, AD; adenocarcinoma, LC; large cell carcinoma, ADSQ; adenosquamous cell carcinoma, MM; malignant mesothelioma, NHF; normal human fibroblast.</p

Ad-REIC induced JNK activation and subsequent apoptosis in NSCLC cells.

<p>(a) Induction of apoptosis after <i>in vitro</i> Ad-REIC treatment as examined in A549 cells using Hoechst 33342 staining. The upper panel indicates the appearance of apoptotic cells after Ad-REIC treatment. The lower panel shows the apoptotic rate of A549 cells after the indicated treatment. A total of 5 different fields were examined under a microscope to determine the apoptotic rate. A significant difference was observed (*p<0.001) between the Ad-LacZ and the Ad-REIC treatment. (bar: 100 µm) (b) Western blot analysis for proteins involved in signal transduction triggered by Ad-REIC. Cells were harvested at 48 h after transfection with Ad-LacZ or Ad-REIC at 20 MOI. (c) H460 cells, which are resistant to adenovirus transduction, were harvested at 48 h after transfection with Ad-LacZ or Ad-REIC at 20, 100, and 200 MOI.</p

Characteristics and the inhibition rate of cell viability on NSCLC cell lines.

<p>NSCLC, non-small cell lung cancer; AD, adenocarcinoma; SQ, squamous cell carcinoma; LC, large cell carcinoma; ADSQ, adeno-squamous cell carcinoma; MM, malignant mesothelioma; NHF, normal human fibroblast; mut, mutation; W/t. wild type; MOI, multiplicity of infection.</p