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51.
Suguru Fukuhara Yuji OshikawaKumade Yasunori Kogure Sumito Shingaki Hirokazu Kariyazono Yoshiya Kikukawa Junji Koya Yuki Saito Mariko Tabata Kota Yoshifuji Kota Mizuno Akiko MiyagiMaeshima Hiromichi Matsushita Masanaka Sugiyama Chitose Ogawa Yoshihiro Inamoto Takahiro Fukuda Masato Sugano Nobuhiko Yamauchi Yosuke Minami Makoto Hirata Teruhiko Yoshida Takashi Kohno Shinji Kohsaka Hiroyuki Mano Yuichi Shiraishi Seishi Ogawa Koji Izutsu Keisuke Kataoka 《Cancer science》2022,113(8):2763
Identification of genetic alterations through next‐generation sequencing (NGS) can guide treatment decision‐making by providing information on diagnosis, therapy selection, and prognostic stratification in patients with hematological malignancies. Although the utility of NGS‐based genomic profiling assays was investigated in hematological malignancies, no assays sufficiently cover driver mutations, including recently discovered ones, as well as fusions and/or pathogenic germline variants. To address these issues, here we have devised an integrated DNA/RNA profiling assay to detect various types of somatic alterations and germline variants at once. Particularly, our assay can successfully identify copy number alterations and structural variations, including immunoglobulin heavy chain translocations, IKZF1 intragenic deletions, and rare fusions. Using this assay, we conducted a prospective study to investigate the feasibility and clinical usefulness of comprehensive genomic profiling for 452 recurrently altered genes in hematological malignancies. In total, 176 patients (with 188 specimens) were analyzed, in which at least one alteration was detected in 171 (97%) patients, with a median number of total alterations of 7 (0–55). Among them, 145 (82%), 86 (49%), and 102 (58%) patients harbored at least one clinically relevant alteration for diagnosis, treatment, and prognosis, respectively. The proportion of patients with clinically relevant alterations was the highest in acute myeloid leukemia, whereas this assay was less informative in T/natural killer‐cell lymphoma. These results suggest the clinical utility of NGS‐based genomic profiling, particularly for their diagnosis and prognostic prediction, thereby highlighting the promise of precision medicine in hematological malignancies. 相似文献
52.
Kuriyama S Kikukawa M Masui K Okuda H Nakatani T Sakamoto T Yoshiji H Fukui H Ikenaka K Mullen CA Tsujii T 《International journal of cancer. Journal international du cancer》1999,81(4):592-597
Murine hepatocellular carcinoma cells were retrovirally transduced with the bacterial cytosine deaminase (CD) gene. CD-transduced cells exhibited more than 120-fold higher sensitivity to 5-fluorocytosine (5-FC) compared with parental cells. When syngeneic immunocompetent mice were inoculated s.c. with parental hepatocellular carcinoma cells containing as little as 5% CD-transduced cells, significant inhibition of tumor formation was induced by 5-FC treatment. Furthermore, established solid tumors in immunocompetent mice containing only 5% CD-transduced cells were infiltrated markedly with CD4- and CD8+ T lymphocytes and macrophages by 5-FC treatment, such that significant reduction or even complete regression of tumors was observed. These tumor-free mice resisted subsequent rechallenge with wild-type tumor. Conversely, when athymic nude mice were inoculated with a cell mixture containing CD-transduced cells and parental cells at a ratio of 40:60, all developed tumors despite 5-FC treatment. Our results indicate that gene therapy using the CD/5-FC system can induce efficient anti-tumor effects and protective immunity in immunocompetent mice but not in athymic immunodeficient mice, suggesting that the host's immunocompetence may be a critical factor for achieving successful gene therapy against cancer. 相似文献
53.
Sugihara S Sekene M Kanatsu H Kitamikado H Kikukawa F Hasegawa K Mori H Isobe K 《Gan to kagaku ryoho. Cancer & chemotherapy》2005,32(Z1):53-55
"Home Remote Medical Support System" (the support system) is an interactive real time communication system, consisting of a vital health measuring device and a near-television quality home digital videophone installed at a residence, to connect a primary medical care institution and a homecare patient by information communication lines. Exclusive use of a telephone, vital health measuring device, TV monitor and camera are installed as home devices to communicate with a primary personal computer at the medical institution to manage patient's data and to have video phone health consultations. We employed and conducted the support system with a help from "the remote medical assistant task" operated by the local government since April 2004. Two patients actually used the support system in the first year although we initially planned to have three. In conclusion, the support system appears to have been useful for the health management of patients with stable conditions. Meanwhile, we have to reassess the application of the support system and to balance its accountability among the user efficiency, the content of the support provider and user expenses. 相似文献
54.
Hitoshi Tanaka Masakazu Sakaguchi Yoshimasa Kikukawa Tsuneyuki Sato Tadatoshi Ota 《Macromolecular chemistry and physics.》1994,195(6):2083-2091
Radical copolymerizations of ring-substituted trans-cinnamonitriles with olefins such as styrene and acrylonitrile were studied at 60°C. The copolymerization parameters of cinnamonitriles (M1) in the copolymerizations with styrene (M2) were determined to be r1 = 0,01 to 0,30, r2 = 0,45 to 4,25, Q1 = 0,06 to 0,70, and e1 = ?0,52 to 1,35. The relative reactivity, log(1/r2), showed a tendency to increase with increasing Hammett constant σ and was higher in conjugated cinnamonitriles than in less conjugated nitriles. For p-substituted cinnamonitriles, ρ and γ values in the equation of log(1/r2) = ρ · σ + γ · ER were estimated to be 0,48 and 2,0, respectively, where ER is a resonance constant. The relative reactivity was also increased with increasing 13C NMR chemical shift of the olefinic β-carbon of cinnamonitriles and decreasing polarity of the solvents used. In addition, the relative reactivity towards a poly(acrylonitrile) radical is higher in cinnamonitrile than in cinnamic esters. The structure of the radical generated by the attack of the 2-methyl-2-propyl radical at the cinnamonitrile was examined by means of electron paramagnetic resonance (EPR) spectroscopy. 相似文献
55.
56.
Takeshi Shiotani Nobuyuki Kawai Morio Sato Hiroyuki Minamiguchi Taizo Takeuchi Hirohiko Tanihata Kazuro Kikukawa Yasunari Uekado Toshiaki Shinka 《Japanese journal of radiology》2009,27(5):218-220
We report a case of leiomyoma of the seminal vesicle in a 74-year-old man who presented with left hemilumbago. Computed tomography
and magnetic resonance imaging revealed a mass containing coarse calcification and low signal intensity areas on T1- and T2-weighted
images. The clinical features of previously reported cases of leiomyoma of the seminal vesicle are presented, including those
of the present case. There remains a lack of consensus regarding surgical resection of leiomyoma of the seminal vesicle. 相似文献
57.
Kawano Y Ueno S Abe M Kikukawa Y Yuki H Iyama K Okuno Y Mitsuya H Hata H 《Oncology reports》2012,27(1):39-44
Skeletal complications represent major clinical problems in multiple myeloma (MM). MM cells are known to induce differentiation of osteoclasts and inhibit osteoblasts. Receptor activator of nuclear factor-κB ligand (RANKL) and osteoprotegerin (OPG) are key molecules for osteoclastogenesis. Although OPG interacts with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), the contribution of TRAIL to skeletal-related events (SRE) remains a matter of debate. In the present study, we examined the role of TRAIL in MM bone lesions. Myeloma cells were purified from 56 MM patients by CD138-immunomagnetic beads. TRAIL, DKK-1 and MIP1α RNA expression in purified MM cells was analyzed by real-time PCR. Immunohistochemistry of TRAIL was performed on paraffin-embedded plasmacytoma tissue sections. The concentration of TRAIL in the serum and bone marrow plasma from MM patients was analyzed by ELISA. TRAIL expression was significantly higher in MM cells than in plasma cells from patients with monoclonal gammopathy of undetermined significance (MGUS). TRAIL staining was detected in the cytoplasm of myeloma cells. TRAIL expression in MM cells correlated with bone marrow plasma TRAIL concentration. TRAIL expression had a positive correlation with osteolytic markers, such as serum calcium and urinary deoxypyridinoline. These results suggest that TRAIL, produced from myeloma cells, may play an important role in bone resorption of MM patients. Inhibition of this pathway may lead to development of a new therapeutic approach preventing bone resorption in MM. 相似文献
58.
Treatment of established collagen induced arthritis with prostaglandin E1 incorporated in lipid microspheres 总被引:1,自引:0,他引:1
Moriuchi-Murakami E Yamada H Ishii O Kikukawa T Igarashi R 《The Journal of rheumatology》2000,27(10):2389-2396
OBJECTIVE: In view of evidence obtained from in vitro and in vivo experiments that prostaglandin E1 (PGE1) has regulatory effects on disordered immune responses and inflammation, we investigated whether lipo-PGE1, an efficient drug delivery system incorporating PGE1 into lipid microspheres, can ameliorate arthritis in the collagen induced arthritis (CIA) model of rheumatoid arthritis (RA). METHODS: DBA/1J male mice were immunized with bovine type II collagen in adjuvant, and treated daily from onset of clinical arthritis with intravenous administration of lipo-PGE1 (5-50 microg/kg) or lipid vehicle as a control. Arthritis was assessed over a 10 day treatment period by monitoring for paw swelling and clinical score. Histopathology of the arthritic hind paws was also evaluated. Lipo-PGE1 accumulation in arthritic joint tissues was measured using 3H labeled PGE1 incorporated in lipid microspheres. RESULTS: Arthritis was significantly suppressed in lipo-PGE1 treated mice compared with lipid vehicle treated controls (p < 0.05, p < 0.016, respectively) in a dose-dependent manner. Histopathological assessment showed a significant reduction of pannus formation and joint destruction in lipo-PGE1 treated mice compared with controls (p < 0.05). Lipo-PGE1 preferentially accumulated in arthritic joints for a longer period than free PGE1. CONCLUSION: Using an efficient drug delivery system, PGE1 can suppress CIA, and lipo-PGE1 may have a potential therapeutic role in RA. 相似文献
59.
Kikukawa M Shin K Iwamoto T Takasaki M Ueda R Suematu N Takahashi A Mori S 《Nihon Ronen Igakkai zasshi. Japanese journal of geriatrics》2003,40(5):515-519
An 82-year-old woman was admitted with fever and anorexia. Aggravated pancytopenia and liver dysfunction suggested the presence of disseminated intravascular coagulation. The serum ferritin level increased to 9,100 ng/ml. Bone marrow aspiration showed an increase of histiocytes with phagocytosis and a diagnosis of hemophagocytic syndrome was made. Symptomatic therapy was performed because of her deteriorated general condition. She died of multiple organ failure, 32 days after admission. Autopsy revealed swollen lymph nodes with proliferation of large neoplastic cells containing rich cytoplasm and pleomorphic and multi-segmented large nuclei. The immunophenotype of the neoplastic cells was LCA-, CD3-, CD5-, CD 20-, CD79a-, UCHL1-, MT1-, CD15-, p80-. Neoplastic cells were positive for CD30, mainly in Golgi apparati, and also positive for EBV-encoded small nonpolyadenylated RNAs (EBER). This case was diagnosed as anaplastic large cell lymphoma (ALCL) associated with hemophagocytic syndrome. It was estimated that Epstein-Barr virus had played an important role in the development of ALCL in the present case. 相似文献
60.
Tomoyo Okuda Akinori Ando Eiji Sakuradani Hiroshi Kikukawa Nozomu Kamada Misa Ochiai Jun Shima Jun Ogawa 《Current genetics》2014,60(3):175-182
An inducible promoter is a useful tool for the controlled expression of a given gene. In this report, we describe galactose-dependent promoters for potential use in an oleaginous fungus Mortierella alpina. We cloned the putative promoter regions of two genes encoding galactose metabolic enzymes, GAL1 and GAL10, from the genome of M. alpina 1S-4. The β-glucuronidase (GUS) reporter gene assay in M. alpina 1S-4 revealed that regulation of these promoters was dependent on the presence of galactose in the medium both with and without other sugars. With the GAL10 promoter, an approximately 50-fold increase of GUS activity was demonstrated by addition of galactose into the culture media at any cultivation phase. The 5′ deletion analysis of the GAL10 promoter revealed that a promoter region of over 2,000 bp length was required for its high-level activity and sufficient inducible response. Significantly, this is the first report of inducible promoters of zygomycetes. The GAL10 promoter will be a valuable tool for gene manipulation in M. alpina 1S-4. 相似文献