Molecular Mechanism of Arsenic Trioxide-Induced Apoptosis in HL-60 and Cell Lines

Recently, it has been reported that arsenic trioxide (As2 O3) is an effective anticancer agent for acute promyelocytic leukemia (APL). In the present study, we examined the anticancer effects of As2 O3 at low concentration (0.25～2.OμM) on two hunan leukemia/lymphoma cell lines, HL-60 and RL, in vitro. We found that As2 O3 inhibited the growth of HL-60 and RL similar to the reported APL cell line, NB4. Typical apoptosis was observed in morphologlcal study and DNA fragmentation assay, as well as a cell cycle arrest at subG1. To address the mechanism of As2 03-induced apoptosis, we also examined the effect of As2 O3 on the CD95/CD95L pathway and bcl-2 protein expression. The results showed that the CD95/CD95L expressions were upregulated; meanwhile, caspase 8 and caspase 3 were activated. However, the bcl-2 protein expression was downregulated. Using anti-CD95 monoclonal antibody to block the CD95　pathway, As2 O3 - induced apoptosis was ameliorated. These data suggest that in HL-60 and RL cell lines the CD95/CD95L pathway and downregulation of bc1-2 protein expression are invoIved in As2 O3-induced apoptosis

Arsenic Trioxide Induces Oncosis in K562 Cell Line Via CD95 CD95L Pathway

Recently it has been reported that arsenic trioxide (As203) is very effective in the treatment of acute promyelocytic leukemia (APL) by inducing apoptosis, but the molecular mechanism of its action on other leukemia remains unclear. In the present study, we tested the effect of As2 O3 at low concentration O.25-2.O μM on K562, a chronic myelogenous leukemia cell line. As2 03 inhibited the cell growth of K562 in a similar way to APL cell line NB4. Typical oncotic cell death, such as cytoplasmic swelling and swelling of organelles, was observed by morphological study and cell cycle was arrested at G2+M phases. During the treatment of As2 03, the CD95 and CD95 ligand (CD95L) expressions were upregulated, and caspase 8 and caspase 3 were activated, but bcl-2 expression was not changed. Treatment of the cells with anti-CD95 monoclonal antibody or ZVAD-fmk capable of blocking the CD95 signaling pathway ameliorated As2 03-induced oncosis. These results suggest that the induction of oncosis by As2 03 invoIves CD95/CD95L pathway in K562 and As2 03 may provide a novel therapy for leukemia other than APL

Noble gases and K-Ar ages of five Rumuruti chondrites Yamato(Y)-75302, Y-791827, Y-793575, Y-82002, and Asuka-881988

Noble gases and K concentrations have been determined for aliquot samples prepared from the five Antarctic R-chondrites Yamato (Y)-75302,Y-791827,Y-793575,Y-82002,and Asuka (A)-881988. K-Ar ages of about 4.2Ga were obtained for Y-75302,Y-791827,Y-793575 and A-881988,while Y-82002 showed a slightly younger age of 3.9Ga. The Y-75302,Y-791827 and Y-82002 are enriched in solar light noble gases. Four meteorites Y-75302,Y-791827,Y-82002 and A-881988 have cosmic-ray exposure ages of about 20Ma, while the age of Y-793575 is about 7Ma. Based on the noble gas compositions and K-Ar ages, Y-75302 and Y-791827 are probably paired and Y-82002 may belong to this pair. Relatively high and variable ^Xe/^Xe ratios between 2-3.7 as well as enrichments of heavier Xe isotopes were observed in all R-chondrites

SFME細胞を用いた造血器腫瘍発がん遺伝子のモニター法の確立

金沢大学医学部1.研究目的:本研究は、Serum-Free Mouse Embryo(SFME)細胞がヒトがん組織由来のがん遺伝子によって形質転換され、容易に同系正常マウスに腫瘍を形成する性質を利用して、造血器腫瘍をはじめとする悪性腫瘍における発癌移伝子のモニター法を確立する目的でなされた。2.SFME細胞の培養条件の確立:SFME細胞の培養にはかなりの熟練を要することが分かったために、種々の培養条件について検討した。その結果、(1)培地に超純水を使用し、添加物(EGFなど)は培地交換時に添加すること、(2)ガラス器具は細胞が付着するために使用しないこと、(3)トリプシンおよびトリプシンインヒビターを加えてからの時間はできるだけ短くし、速やかに次のステップに入ること、などを厳守することにより順調に培養できるようになった。現在では、必要に応じて細胞が供給可能になっている。3.ヒトがん遺伝子により形質転換:SFME細胞に、ヒト膀胱癌T24由来活性型H-ras1遺伝子とマウスc-mycを導入して得られた形質転換細胞をBALB/cマウスに移植し腫瘍を形成した。10^6個/マウスの細胞を移植することにより、腫瘍を形成可能であることが確認された。4.形質転換した細胞の性状の検討:形質転換細胞をマウス皮下に接種し、経時的に各臓器への浸潤を観察したところ高頻度に肺に転移する細胞(r/mHM-SFME-1)を発見した。この細胞とPCR法を組み合わせて、臓器(今回は肺)に転移した腫瘍細胞の数を算定することを試みた。その結果、マウス一匹の肺内に1×10^4個の腫瘍細胞が存在すればDNA上検出可能であることが明らかになった。5.ヒト造血器腫瘍への応用:現在ヒト白血病細胞からがん遺伝子を抽出しているが、これを用いてSFME細胞を形質転換し、今回の方法を応用することで治療効果の判定とともに、微量残存腫瘍細胞の量的解析が可能になると考える。1. Objective: In this study, it has been attempted to establish an useful method for monitoring oncogenes in hematologic and other malignancies using Serum-Free Mouse Embryo (SFME) cells which are readily transformed by human cancer cells-derived proto-oncogenes.2. Establishment of culture condition of SFME cells: First, in order to obtain the best culture condition for SFME cells, the cells were cultured under various conditions. It became clear that it is essential to use purified water for cultures and to add various additives (EGF etc.) at the time of medium exchange. Furthermore, a glass apparatus is not suitable for culturing SFME.3. Tumorigenicity of H-ras and c-myc proto-oncogenes-transformed SFME cells: It was confined that transformed SFME cells are transplantable to syngeneic mouse (BALB/C), and are able to develop tumor in mouse.4. Characteristics of transformed SFME cells: Transformed SFME cells were injected subcutaneously into BALB/C mouse and patterns of involvement in the various organs were observed sequentially. Consequently,a transformed cell line which frequently metastasize to the lung (r/mHM-SFME-1) were established. In an attempt to develop a gene-monitoring system, numbers of metastasized r/mHM-SFME-1 cells in the lung of BALB/C were analyzed using PCR method. The detectable minimum number of metastasized cells in the lung per mouse was 1X10^4 cells, and there was a linear correlation between the amount of DNA and a number of metastasized cell.5. Application of this system for oncogene monitor in hematologic malignancies: Analizing SFME cells transformed by human leukemic cells-derived proto-oncogene make it possible to evaluate chemotherapeutic effects and to detect minimal residual disease readily.研究課題/領域番号:03671181, 研究期間(年度):1991 – 1992出典：研究課題「SFME細胞を用いた造血器腫瘍発がん遺伝子のモニター法の確立」課題番号03671181（KAKEN：科学研究費助成事業データベース（国立情報学研究所）） （https://kaken.nii.ac.jp/ja/report/KAKENHI-PROJECT-03671181/036711811992kenkyu_seika_hokoku_gaiyo/）を加工して作

抗腫瘍剤による腫瘍細胞の形態学的変化に関する研究

金沢大学医学部研究課題/領域番号:X00210----077153, 研究期間(年度):1975出典：「抗腫瘍剤による腫瘍細胞の形態学的変化に関する研究」研究成果報告書　課題番号：X00210----077153（KAKEN：科学研究費助成事業データベース（国立情報学研究所）） （https://kaken.nii.ac.jp/ja/grant/KAKENHI-PROJECT-X00210----077153/）を加工して作

The Effect of Local Structure and Non-uniformity on Decoherence-Free States of Charge Qubits

We analyze robustness of decoherence-free (DF) subspace in charge qubits when there are a local structure and non-uniformity that violate collective decoherence measurement condition. We solve master equations of up to four charge qubits and a detector as two serially coupled quantum point contacts (QPC) with an island structure. We show that robustness of DF states is strongly affected by local structure as well as by non-uniformities of qubits

Optimization temperature sensitivity using the optically detected magnetic resonance spectrum of a nitrogen-vacancy center ensemble

Temperature sensing with nitrogen vacancy (NV) centers using quantum techniques is very promising and further development is expected. Recently, the optically detected magnetic resonance (ODMR) spectrum of a high-density ensemble of the NV centers was reproduced with noise parameters [inhomogeneous magnetic field, inhomogeneous strain (electric field) distribution, and homogeneous broadening] of the NV center ensemble. In this study, we use ODMR to estimate the noise parameters of the NV centers in several diamonds. These parameters strongly depend on the spin concentration. This knowledge is then applied to theoretically predict the temperature sensitivity. Using the diffraction-limited volume of 0.1 micron^3, which is the typical limit in confocal microscopy, the optimal sensitivity is estimated to be around 0.76 mK/Hz^(1/2) with an NV center concentration of 5.0e10^17/cm^3. This sensitivity is much higher than previously reported sensitivities, demonstrating the excellent potential of temperature sensing with NV centers.Comment: 17 pages, 4 figures, 1 tabl