Noriko Saidoh

Isocitrate dehydrogenase mutation is frequently observed in giant cell tumor of bone

Giant cell tumors of bone (GCTB) are benign and locally destructive tumors that include osteoclast‐type multinuclear giant cells. No available treatment is definitively effective in curing GCTB, especially in surgically unresectable cases. Isocitrate dehydrogenase (IDH) mutations have been reported not only in gliomas and acute myeloid leukemias, but also in cartilaginous tumors and osteosarcomas. However, IDH mutations in GCTB have not been investigated. The IDH mutations are remarkably specific to arginine 132 (R132) in IDH1 and arginine 172 (R172) or arginine 140 (R140) in IDH2; IDH1/2 mutations are known to convert α‐ketoglutarate to oncometabolite R(‐)‐2‐hydroxyglutarate. We recently reported that the most frequent IDH mutation in osteosarcomas is IDH2‐R172S, which was detected by MsMab‐1, a multispecific anti‐IDH1/2 mAb. Herein, we newly report the IDH mutations in GCTB, which were stained by MsMab‐1 in immunohistochemistry. DNA direct sequencing and subcloning identified IDH mutations of GCTB as IDH2‐R172S (16 of 20; 80%). This is the first report to describe IDH mutations in GCTB, and MsMab‐1 can be anticipated for use in immunohistochemical determination of IDH1/2 mutation‐bearing GCTB.

Novel Monoclonal Antibody LpMab-17 Developed by CasMab Technology Distinguishes Human Podoplanin from Monkey Podoplanin

Podoplanin (PDPN) is a type-I transmembrane sialoglycoprotein, which possesses a platelet aggregation-stimulating (PLAG) domain in its N-terminus. Among the three PLAG domains, O-glycan on Thr52 of PLAG3 is critical for the binding with C-type lectin-like receptor-2 (CLEC-2) and is essential for platelet-aggregating activity of PDPN. Although many anti-PDPN monoclonal antibodies (mAbs) have been established, almost all mAbs bind to PLAG domains. We recently established CasMab technology to produce mAbs against membranous proteins. Using CasMab technology, we produced a novel anti-PDPN mAb, LpMab-17, which binds to non-PLAG domains. LpMab-17 clearly detected endogenous PDPN of cancer cells and normal cells in Western-blot, flow cytometry, and immunohistochemistry. LpMab-17 recognized glycan-deficient PDPN in flow cytometry, indicating that the interaction between LpMab-17 and PDPN is independent of its glycosylation. The minimum epitope of LpMab-17 was identified as Gly77-Asp82 of PDPN using enzyme-linked immunosorbent assay. Of interest, LpMab-17 did not bind to monkey PDPN, whereas the homology is 94% between human PDPN and monkey PDPN, indicating that the epitope of LpMab-17 is unique compared with the other anti-PDPN mAbs. The combination of different epitope-possessing mAbs could be advantageous for the PDPN-targeting diagnosis or therapy.

Fabrication and nano-imprintabilities of Zr-, Pd- and Cu-based glassy alloy thin films

With the aim of investigating nano-imprintability of glassy alloys in a film form, Zr(49)Al(11)Ni(8)Cu(32), Pd(39)Cu(29)Ni(13)P(19) and Cu(38)Zr(47)Al(9)Ag(6) glassy alloy thin films were fabricated on Si substrate by a magnetron sputtering method. These films exhibit a very smooth surface, a distinct glass transition phenomenon and a large supercooled liquid region of about 80 K, which are suitable for imprinting materials. Moreover, thermal nano-imprintability of these obtained films is demonstrated by using a dot array mold with a dot diameter of 90 nm. Surface observations revealed that periodic nano-hole arrays with a hole diameter of 90 nm were successfully imprinted on the surface of these films. Among them, Pd-based glassy alloy thin film indicated more precise pattern imprintability, namely, flatter residual surface plane and sharper hole edge. It is said that these glassy alloy thin films, especially Pd-based glassy alloy thin film, are one of the promising materials for fabricating micro-machines and nano-devices by thermal imprinting.

Fabrication of nanodot array mold with 2 Tdot/in.2 for nanoimprint using metallic glass

Here, the authors fabricated a mold consisting of nanodot arrays with an 18-nm pitch and performed nanoimprinting of metallic glass for developing bitpatterned media (BPM) with an areal recording density of 2 Tbit/in.2. Specifically, they investigated the feasibility of SiO2/Si mold fabrication by metal mask patterning with focused ion beam assisted chemical vapor deposition (FIB-CVD) and reactive ion etching (RIE). SiO2 was etched with a mixed gas of CHF3 and O2, resulting in successful fabrication of convex nanodot arrays with an 18-nm pitch. The authors attempted nanoimprinting of Pd-based metallic glass with the fabricated SiO2 mold and clearly confirmed the replication of the fine nanohole pattern. These results suggest that the proposed FIB-CVD and RIE process is a promising method for fabricating ultrafine nanodot arrays and that metallic glasses are excellent nanoimprintable materials for mass-produced nanodevices such as BPM with ultrahigh recording density.

Fabrication of Molds with 25-nm Dot-Pitch Pattern by Focused Ion Beam and Reactive Ion Etching for Nanoimprint Using Metallic Glass

Here we attempted to fabricate molds (dies) of nanodot arrays with a 25-nm pitch and to nanoimprint metallic glass for developing bit-patterned media with an ultrahigh recording density of 1 Tbit/in.2. The mold-fabricating process consisted of mask patterning by focused ion beam assisted chemical vapor deposition (FIB-CVD) and reactive ion etching (RIE). We investigated the feasibility of a Pt-deposited metal etching mask on SiO2 on Si and diamond like carbon (DLC) on Al2O3 substrates, and achieved isolated convex nanodot arrays with a 25-nm pitch and an aspect ratio of 1.8 by RIE with O2 plasma on a DLC/Al2O3 substrate. Subsequently, we nanoimprinted Pt-based metallic glass by using the fabricated molds and successfully replicated fine concave nanohole arrays. The results suggest that the FIB-CVD/RIE process is a promising technique for fabricating ultrafine nanopatterned molds, and metallic glasses are ideal nanoimprintable materials for mass producing nanodevices such as bit-patterned media.