Heat-induced Signal Transduction Pathways Leading to Cell Death and Cell Survival in Cancer Cells

In recent years, cancer therapy research has focused on molecular targets. For efficient hyperthermic cancer therapy, potential targets of interest are molecules which respond to heat and selectively activate signal transduction factors which can inhibit cancer cell proliferation. Signal transduction pathways affected by heat include p53 mediated pathways, JNK (Jun N-terminal kinase) mediated pathways, Akt (protein kinase B) mediated pathways, NBS1 (Nijimegen breakage syndrome 1) mediated pathways, classic MAP (mitogen activated protein) kinase mediated pathways, and p38 MAP kinase mediated pathways. Events such as cell death, cell survival, cell proliferation, and/or cell cycle arrest can be affected by these pathways. To learn more about heat-induced gene and protein expression, cDNA arrays and protein microarrays were used to study cellular responses to heat. This paper briefly reviews interactions of pro- and anti-apoptotic genes and proteins which are induced by heat shock and are components of signal transduction pathways.著作権者：日本ハイパーサーミア学会日本ハイパーサーミア学会及び著作者の許諾を得て登

Postprandial Hypotension due to a Lack of Sympathetic Compensation in Patients with Diabetes Mellitus.

Postprandial hypotension is an important hemodynamic abnormality in diabetes mellitus, but few reports are available on the relationship between autonomic dysfunction and postprandial hypotension. Ten diabetic patients and 10 healthy volunteers were recruited for this study. Postural blood pressure and heart rate changes were measured before lunch, and then the hemodynamic responses to a standardized meal were investigated. Holter electrocardiogram (ECG) monitoring was conducted for assessing spectral powers and time-domain parameters of RR variations. Postural changes from the supine to the upright position decreased the systolic blood pressure of the diabetics from 133(+-)16 to 107(+-)20 mmHg (p<0.01), but did not decrease the systolic blood pressure of the controls. The heart rate remained constant in the diabetics but was increased in the controls. Food ingestion decreased systolic blood pressure in the diabetics, with a maximum reduction of 25(+-)5 mmHg. This decrease was not associated with any changes in the ratio of low frequency to high frequency, and yet the heart rate remained almost constant. Indexes involving parasympathetic tone were not affected. Food ingestion did not affect blood pressure in the control group. These findings suggest that lack of compensatory sympathetic activation is a factor contributing to postprandial hypotension in diabetics, and that parasympathetic drive does not make a significant contribution to this condition

Formation Range, Mechanical Properties and Thermal Stability of Superconducting Zr-Si Amorphous Alloys

New type of refractory metal-metalloid amorphous alloys containing less than 20 at% Si have been found in binary Zr-Si system by a modified melt-spinning technique for high melting point alloys. Specimens are in the form of continuous ribbons of 1-2 mm width and 0.02-0.03 mm thickness. The silicon content in the amorphous range is limited to the range 12 to 24 at%. The Vickers hardness increases from 395 to 495 DPN with increasing silicon content and the tensile strength is of the order of 1400 MPa. Crystallization temperature is the lowest (720 K) at Zr_Si_, increases with decreasing and increasing silicon content and reaches 804 K at Zr_Si_ and 768 K at Zr_Si_. The activation energy for crystallization is in the range 175 to 202 kJ/mol. These amorphous alloys are so ductile that no cracks are observed even after closely contacted bending test. The good ductility remains unchanged for 3.6 ks at temperatures below 650 K. Further, these amorphous alloys exhibit a superconducting transition which occurs very sharply. The superconducting transition temperature (T_c) increases with decreasing silicon content and reaches a maximum value of 3.2 K for Zr_Si_. Thus, the Zr-Si amorphous alloys are a superconductor which possesses the T_c values higher than zirconium metal in addition to high strength combined with good ductility

Thin film write head field analysis using a benchmark problem

A benchmark problem has been proposed by the Storage Research Consortium (SRC) in Japan, for evaluating the applicability of computer codes to 3-D nonlinear eddy current analysis of thin film magnetic recording write head. Various codes using the finite element method are compared in terms of the write head field and the computational efficiency. The difficulty in 3-D mesh generation of thin film head is also discussed. The write head fields calculated by various codes using different meshes show fairly good agreement. The calculated write head fields are verified by measurement using a stroboscopic electron beam tomography. It is found that the calculation time strongly depends on unknown variables </p

Glycerol as a chemical chaperone enhances radiation-induced apoptosis in anaplastic thyroid carcinoma cells

INTRODUCTION: Anaplastic thyroid carcinoma, which is one of the most aggressive, malignant tumors in humans, results in an extremely poor prognosis despite chemotherapy and radiotherapy. The present study was designed to evaluate therapeutic effects of radiation by glycerol on p53-mutant anaplastic thyroid carcinoma cells (8305c cells). To examine the effectiveness of glycerol in radiation induced lethality for anaplastic thyroid carcinoma 8305c cells, we performed colony formation assay and apoptosis analysis. RESULTS: Apoptosis was analyzed with Hoechst 33342 staining and DNA ladder formation assay. 8305c cells became radiosensitive when glycerol was added to culture medium before X-ray irradiation. Apoptosis was induced by X-rays in the presence of glycerol. However, there was little apoptosis induced by X-ray irradiation or glycerol alone. The binding activity of whole cell extracts to bax promoter region was induced by X-rays in the presence of glycerol but not by X-rays alone. CONCLUSION: These findings suggest that glycerol is effective against radiotherapy of p53-mutant thyroid carcinomas

Superconducting Properties of Metastable bcc Solid Solution in Melt-quenched Zr-Ge Binary Alloys

Superconducting metastable bcc phase has been found in rapidly quenched Zr-Ge binary alloys in a composition range 9 to 12 at% Ge. With decreasing germanium content, the T_c value of the bcc alloys increased from 3.30 to 3.88 K, while the H_ gradient at T_c, -(dH_/dT)_, and the electrical resistivity at 4.2 K, ρ_n, decreased from 1.86×10^6 to 1.79×10^6 Am^ K^ and 2.00 to 1.70 μΩm, respectively. There existed a strong correlation between ρ_n, T_c and -(dH_/dT)_; with increasing ρ_n, T_c decreased and - (dH_/dT)_ increased. A correlation between the temperature coefficient of resistivity (TCR), 1/ρ_ (dρ/dT) and T_c was also found ; the larger the TCR the higher is the T_c. The existence of such correlations was inferred to originate from the close relation between the electron-phonon coupling constant λ and ρ_n or TCR. The electronic dressed density of states at the Fermi level N(E_f) (1+λ) was calculated from the experimentally measured values of -(dH_/dT)_ and ρ_n by using theories for strong-coupling superconductors. It was found that the values of N(E_f)(1+λ) significantly reflect T_c. The GL parameter k and the GL coherence length ζ_(0) were estimated to be 69-79 and about 7.5 nm, respectively, from the experimental values of -(dH_/dT)_ and σ_n. The metastable bcc Zr-Ge alloys are concluded to be extremely "dirty" type-II superconductors

p53 変異型ヒト口腔がん細胞における高LET 放射線によるp53 非依存Akt 生存シグナルの抑制

Although mutations and deletions in the p53 tumor suppressor gene lead to resistance to low linear energy transfer (LET) radiation, high-LET radiation efficiently induces cell lethality and apoptosis regardless of the p53 gene status in cancer cells. Recently, it has been suggested that the induction of p53-independent apoptosis takes place through the activation of Caspase-9 which results in the cleavage of Caspase-3 and poly (ADP-ribose) polymerase (PARP). This study was designed to examine if high-LET radiation depresses serine/threonine protein kinase B (PKB, also known as Akt) and Akt-related proteins. Human gingival cancer cells (Ca9-22 cells) harboring a mutated p53 (mp53) gene were irradiated with 2 Gy of X-rays or Fe-ion beams. The cellular contents of Akt-related proteins participating in cell survival signaling were analyzed with Western Blotting 1, 2, 3 and 6h after irradiation. Cell cycle distributions after irradiation were assayed with flow cytometric analysis. Akt-related protein levels decreased when cells were irradiated with high-LET radiation. High-LET radiation increased G(2)/M phase arrests and suppressed the progression of the cell cycle much more efficiently when compared to low-LET radiation. These results suggest that high-LET radiation enhances apoptosis through the activation of Caspase-3 and Caspase-9, and suppresses cell growth by suppressing Akt-related signaling, even in mp53 bearing cancer cells.博士（医学）・甲第598号・平成25年3月15日Copyright © 2012 Elsevier Inc. All rights reserve

Probiotics into outer space: feasibility assessments of encapsulated freeze-dried probiotics during 1 month’s storage on the International Space Station

Suppression of immune function during long spaceflights is an issue that needs to be overcome. The well-established probiotic Lactobacillus casei strain Shirota (LcS) could be a promising countermeasure, and we have launched a project to investigate the efficacy of its use on the International Space Station (ISS). As a first step, we developed a specialist probiotic product for space experiments, containing freeze-dried LcS in capsule form (Probiotics Package), and tested its stability through 1 month of storage on the ISS. The temperature inside the ISS ranged from 20.0 to 24.5 °C. The absorbed dose rate of the flight sample was 0.26 mGy/day and the dose equivalent rate was 0.52 mSv/day. The number of live LcS was 1.05 × 1011 colony-forming units/g powder (49.5% of the initial value) 6 months after the start of the study; this value was comparable to those in the two ground controls. Profiles of randomly amplified polymorphic DNA, sequence variant frequency, carbohydrate fermentation, reactivity to LcS-specific antibody, and the cytokine-inducing ability of LcS in the flight sample did not differ from those of the ground controls. We can therefore maintain the viability and basic probiotic properties of LcS stored as a Probiotics Package on the ISS