Anti-Tumor Effect against Human Cancer Xenografts by a Fully Human Monoclonal Antibody to a Variant 8-Epitope of CD44R1 Expressed on Cancer Stem Cells

BACKGROUND: CD44 is a major cellular receptor for hyaluronic acids. The stem structure of CD44 encoded by ten normal exons can be enlarged by ten variant exons (v1-v10) by alternative splicing. We have succeeded in preparing MV5 fully human IgM and its class-switched GV5 IgG monoclonal antibody (mAb) recognizing the extracellular domain of a CD44R1 isoform that contains the inserted region coded by variant (v8, v9 and v10) exons and is expressed on the surface of various human epithelial cancer cells. METHODS AND PRINCIPAL FINDINGS: We demonstrated the growth inhibition of human cancer xenografts by a GV5 IgG mAb reshaped from an MV5 IgM. The epitope recognized by MV5 and GV5 was identified to a v8-coding region by the analysis of mAb binding to various recombinant CD44 proteins by enzyme-linked immunosorbent assay. GV5 showed preferential reactivity against various malignant human cells versus normal human cells assessed by flow cytometry and immunohistological analysis. When ME180 human uterine cervix carcinoma cells were subcutaneously inoculated to athymic mice with GV5, significant inhibition of tumor formation was observed. Furthermore, intraperitoneal injections of GV5markedly inhibited the growth of visible established tumors from HSC-3 human larynx carcinoma cells that had been subcutaneously transplanted one week before the first treatment with GV5. From in vitro experiments, antibody-dependent cellular cytotoxicity and internalization of CD44R1 seemed to be possible mechanisms for in vivo anti-tumor activity by GV5. CONCLUSIONS: CD44R1 is an excellent molecular target for mAb therapy of cancer, possibly superior to molecules targeted by existing therapeutic mAb, such as Trastuzumab and Cetuximab recognizing human epidermal growth factor receptor family

金沢大学における携帯型パソコン必携化に関する12年間の取組

金沢大学総合メディア基盤センター近年，ICTの技術的発展と社会的浸透によって，教育への情報化の推進などの取組が着実に進められつつある．特にSociety4.0（情報化社会）からSociety5.0に向けた人材育成は急務といわれている．そのための前段として携帯型パソコン必携化のような取組は，必要不可欠なものになるだろう．そこで，本稿にて，金沢大学で平成18年度から12年間実施してきた新入学生に携帯型パソコン必携化を軸に，ICTに関するさまざまな方策を紹介し，併せてそれら上手に活用させるためのICT活用教育実施とサポート体制について紹介する

Anionic Polymerization Mechanism of Acrylonitrile Trimer Anions : Key Branching Point between Cyclization and Chain Propagation

A cluster anion of vinyl compounds in the gaseous phase has served as one of the simplest microscopic models of the initial stages of anionic polymerization. Herein, we describe our investigations into the initial stage mechanisms of anionic polymerization of acrylonitrile (AN; CH2=CHCN) trimer anions. While the cyclic oligomer is found in mass and photoelectron spectroscopic studies of (AN)3-, only the chain oligomer is found in the infrared photodissociation (IRPD) spectrum of Ar-tagged (AN)3-. Based on the calculated polymerization pathway of (AN)3-, we consider that the chain oligomers are the reaction intermediates in the cyclization of (AN)3-. The rotational isomerization of the (AN)3- chain oligomer is found to be the bottleneck in the cyclization of (AN)3-. To form the (AN)4- chain oligomer by chain propagation, the addition of an AN molecule to (AN)3- should occur prior to the rotational isomerization. We conclude that the rotational isomerization in the (AN)3- chain oligomer is the key branching point between cyclization (termination) or chain propagation in the anionic polymerization.This is a preprint of an article published by American Chemical Society in Journal of Physical Chemistry A, 2012, available online: http://pubs.acs.org/doi/abs/10.1021/jp305291r

Dosimetry for a microbeam array generated by synchrotron radiation at SPring-8

A microbeam array was formed with a multi-slit collimator (MSC) for research on radiation therapy (MRT). Kodak EDR2 film was used to measure the dose distribution of the microbeam array. The calibration curve of optical density of the film with respect to a dose was established using a standard Farmer chamber and 60Co gamma-ray source. The peak dose of 3.6 Gy/s at the maximum was derived from the film dosimetry using the calibration curve. The uncertainty was estimated to be 5 % which was mainly attributed to the uncertainty of the calibration. It was found that the ionization chamber used for monitoring the dose during the MRT experiments gave lower dose by about 30 % than the dose derived from the film dosimetry

The PCC assay can be used to predict radiosensitivity in biopsy cultures irradiated with different types of radiation

It has been studied to identify potential biomarkers for radiosensitivity using the relationship between cell killing and the yield of excess chromatin fragments detected with the premature chromosome condensation (PCC) technique. This method will be applied to primary cultured cells obtained from biopsies from patients. Six primary culture biopsies were obtained from 6 patients with carcinoma of the cervix before starting radiotherapy. The cultures were irradiated with two different LET carbon-ion beams (LET= 13 keV/µm, 77.1+2.8 keV/µm) and 200kV X rays. The carbon-ion beams were produced by the Heavy Ion Medical Accelerator in Chiba (HIMAC). PCC was performed using the polyethylene glycol-mediated cell fusion technique. The yield of excess chromatin fragments were measured by counting the number of unrejoined chromatin fragments detected with the PCC technique after a 24-hour post-irradiation incubation period. Obtained results indicated that cultures, which were more sensitive to killing, were also more susceptible to the induction of excess chromatin fragments. Furthermore there was a good correlation between cell killing and excess chromatin fragments among the 6 cell cultures examined. There is also evidence that the induction of excess chromatin fragments was increasing with increasing LET as well as cell-killing effect in the same cell culture. The data reported here support the idea that the yield of excess chromatin fragments detected with the PCC technique might be useful for predicting radiosensitivity of cells contained in tumor tissue, and to predict responses to different radiation types