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RUNX1–Survivin Axis Is a Novel Therapeutic Target for Malignant Rhabdoid Tumors
Masamitsu Mikami,Tatsuya Masuda,Takuya Kanatani,Katsutsugu Umeda,Hidefumi Hiramatsu,Hirohito Kubota,Tomoo Daifu,Atsushi Iwai,Etsuko Yamamoto Hattori,Kana Furuichi,Saho Takasaki,Sunao Tanaka,Yasuzumi M 한국분자세포생물학회 2022 Molecules and cells Vol.45 No.12
Malignant rhabdoid tumor (MRT) is a highly aggressive pediatric malignancy with no effective therapy. Therefore, it is necessary to identify a target for the development ofnovel molecule-targeting therapeutic agents. In this study, we report the importance of the runt-related transcription factor 1 (RUNX1) and RUNX1–Baculoviral IAP (inhibitor of apoptosis) Repeat-Containing 5 (BIRC5/survivin) axis in the proliferation of MRT cells, as it can be used as an ideal target for anti-tumor strategies. The mechanism of this reaction can be explained by the interaction of RUNX1 with the RUNX1-binding DNA sequence located in the survivin promoter and its positive regulation. Specific knockdown of RUNX1 led to decreased expression of survivin, which subsequently suppressed the proliferation of MRT cells in vitro and in vivo. We also found that our novel RUNX inhibitor, Chb-M, which switches off RUNX1 using alkylating agent-conjugated pyrrole-imidazole polyamides designed to specifically bind to consensus RUNX-binding sequences (5′-TGTGGT-3′), inhibited survivin expression in vivo. Taken together, we identified a novel interaction between RUNX1 and survivin in MRT. Therefore the negative regulation of RUNX1 activity may be a novel strategy for MRT treatment
Shimizu Takayoshi,Fujibayashi Shunsuke,Masuda Soichiro,Kimura Hiroaki,Ishibe Tatsuya,Ota Masato,Tamaki Yasuyuki,Onishi Eijiro,Ito Hideo,Otsuki Bungo,Murata Koichi,Matsuda Shuichi 대한척추외과학회 2022 Asian Spine Journal Vol.16 No.6
Study Design: A retrospective multicenter case series was conducted.Purpose: This study was designed to investigate the clinical features and surgical outcomes of lower lumbar osteoporotic vertebral collapse (LL-OVC) with symptomatic stenosis based on various surgical procedures and classify them using the newly developed collapse severity criteria.Overview of Literature: The surgical outcomes of LL-OVC with symptomatic stenosis remain unclear.Methods: We investigated patients who underwent surgical intervention for LL-OVC (L3, L4, and/or L5) with symptomatic foraminal and/or central stenosis from eight spine centers. Only patients with a minimum follow-up duration of 1 year were included. We developed new criteria to grade vertebral collapse severity (grade 1, 0%–25%; grade 2, 25%–50%; grade 3, 50%–75%; and grade 4, 75%–100%). The clinical features and outcomes were compared based on the collapse grade and surgical procedures performed (i.e., decompression alone, posterior lateral fusion [PLF], lateral interbody fusion [LIF], posterior/transforaminal interbody fusion [PLIF/TLIF], or vertebral column resection [VCR]).Results: In this study, 59 patients (average age, 77.4 years) were included. The average follow-up period was 24.6 months. The clinical outcome score (Japanese Orthopaedic Association score) was more favorable in the LIF and PLIF/TLIF groups than in the decompression alone, PLF, and VCR groups. The use of VCR was associated with a high rate of revision surgery (57.1%). No significant difference in clinical outcomes was observed between the collapse grades; however, grade 4 collapse was associated with a high rate of revision surgery (40.0%).Conclusions: When treating LL-OVC, appropriate instrumented reconstruction with rigid intervertebral stability is necessary. According to our newly developed criteria, LIF may be a surgical option for any collapse grade. The use of VCR for grade 4 collapse is associated with a high rate of revision.
Kurokawa, Kenji,Ryu, Kyoung-Hwa,Ichikawa, Rie,Masuda, Akiko,Kim, Min-Su,Lee, Hanna,Chae, Jun-Ho,Shimizu, Takashi,Saitoh, Tatsuya,Kuwano, Koichi,Akira, Shizuo,Dohmae, Naoshi,Nakayama, Hiroshi,Lee, Bok American Society for Biochemistry and Molecular Bi 2012 The Journal of biological chemistry Vol.287 No.16