https://ir.ymlib.yonsei.ac.kr/handle/22282913/168856 2026-05-15T01:34:07Z https://ir.ymlib.yonsei.ac.kr/handle/22282913/211412 Title: ATP release mediated by TRPM3 enhances invasion in glioblastoma Authors: Bae, Kkot Garam; Song, Chae Won; Yoo, Jae Hong; Lee, Myunghoon; Koo, Noah; Lee, Gangsan; Park, Yongmin Mason; Yoo, Jihwan; Hwang, In-Young; Woo, Dong Ho; Lee, C. Justin; Han, Kyung-Seok Abstract: Glioblastoma (GBM) is the most aggressive and lethal form of primary brain tumor, characterized by uncontrolled proliferation and invasion into surrounding brain tissue. Mechanical stimulation (MS) in the tumor microenvironment (TME) has been correlated to tumor progression, partly via ATP release. However, the underlying molecular mechanisms remain poorly understood. In this study, we found that transient receptor potential melastatin 3 (TRPM3) channel mediates MS-induced ATP release from GBM cells. Genetic knockdown of TRPM3 significantly attenuated ATP release and suppressed GBM cell invasion, indicating its functional relevance in tumor dissemination. Furthermore, TRPM3 regulated ATP release in a Ca2+-independent manner, suggesting a noncanonical mechanism of mechanosensitive signaling. Consequently, targeting TRPM3 may offer a novel target to reduce the invasion of GBM within the TME. 2026-12-01T00:00:00Z https://ir.ymlib.yonsei.ac.kr/handle/22282913/211455 Title: Low-dose radiation generated ROS-activatable doxorubicin prodrug loaded liposome nanoparticles for triple-negative breast cancer treatment Authors: Lim, Hwanju; Moon, Yujeong; Han, Sangheon; Cho, Hanhee; Song, Sunejeong; Kim, Jinseong; Goo, Jagyeong; Shim, Nayeon; Guo, Lili; Kim, Tae-il; Chang, Won Seok; Koh, Won-Gun; Kim, Kwangmeyung Abstract: Triple-negative breast cancer (TNBC) treatment is frequently limited by both intrinsic resistance and normal tissue toxicity in radiation therapy (RT) and chemotherapy. Herein, we report reactive oxygen species (ROS)activatable DOX prodrug loaded liposome nanoparticles (ROS-LNPs) for precision therapy against TNBC. First, the ROS-activatable DOX prodrug was prepared by chemically conjugating caspase-3-cleavable peptide (AcetylLys-Gly-Asp-Glu-Val-Asp, KGDEVD) to DOX using self-immolative PABC linker, resulting in DEVD-DOX. The prodrug of DEVD-DOX is inactive and nontoxic in cancer cells, but it exhibits ROS-activatable cytotoxicity following low-dose radiation. Second, DEVD-DOX is encapsulated into 1,2-dioleoyl-sn-glycero-3-phospho-Lserine (PS)-containing liposome nanoparticles (ROS-LNPs) to improve blood stability and uniformly penetrate into tumor tissue. The resulting ROS-LNPs form very stable nanoparticles with an average diameter of 108.1 +/- 7.3 nm. In particular, ROS-LNPs exhibit low-dose radiation (5 Gy) generated ROS-activatable cytotoxicity in 4 T1 cells, wherein ROS-induced activated caspase-3 can cleave DEVD-DOX released from ROS-LNPs into free DOX that further shows the ROS-induced amplified cytotoxicity without lose-dose radiation. To overcome physiological barriers of the tumor targeting of ROS-LNPs in tumor microenvironment (TME), micro-syringe chip (MSC)-mediated intratumoral delivery strategy is employed to ensure uniform intratumoral delivery. MSCmediated intratumoral administration of ROS-LNPs exhibit 3.26-fold higher tumor-targeting efficiency than conventional intratumoral administration in 4 T1 tumor-bearing mice. The combination of ROS-LNPs and lowdose radiation greatly suppresses tumor growth with potential anticancer immunity, such elevated ICD, dendritic cell (DC) activation, and cytotoxic T cell infiltration, in 4 T1 tumor-bearing mice. Furthermore, the combination of ROS-LNPs and low-dose radiation exhibits the minimal off-target toxicity in normal tissues. This study highlights the clinical potential of ROS-activable doxorubicin loaded liposome nanoparticles as a promising stimulus-responsive platform to bridge the gap between low-dose RT and precision chemotherapy in TNBC treatment. 2026-05-01T00:00:00Z https://ir.ymlib.yonsei.ac.kr/handle/22282913/211969 Title: Analysis of skull base reconstruction methods in huge cranial-nasal communication defect: Bilateral reverse temporalis muscle flap and free flap Authors: Nuch, Kong Srey; Hong, Jong Won; Lee, Won Jai; Chang, Jong Hee; Kim, Chang Hoon Abstract: Background: Effective skull base reconstruction for huge cranial-nasal defects is critical to restoring function and esthetics and preventing complications, such as cerebrospinal fluid (CSF) leakage and ascending infection. We introduced and evaluated two advanced surgical methods of reconstruction: bilateral reverse temporalis muscle flaps and free flaps. Methods: A retrospective review of 16 patients (11 males and 5 females) who underwent skull base reconstruction from January 2017 to December 2024 was conducted. Bilateral reverse temporalis muscle flaps or free flaps, predominantly anterolateral thigh flaps and one rectus myocutaneous flap, were used. Data included patient demographics, defect origins, pathological lesions, reconstruction methods, and postoperative outcomes. Results: Huge cranial-nasal defects resulted from benign tumors (n=3), malignant tumors (n=10), or mucocele/infection (n=3). The defect originated from the nasal cavity (n=12), and the cranium (n=4), with an average defect size of 23.8 +/- 9.3 cm2. Reconstruction was performed using bilateral reverse temporalis muscle flaps (n=6) or free flaps (n=10). Both reconstruction methods effectively prevented CSF leakage and ensured primary healing. Complication rates were comparable, with free flap reconstructions associated with fewer postoperative issues. There were no significant differences in operation times or hospital stays between the two techniques. Conclusion: Bilateral reverse temporalis muscle and free flaps were both effective for skull base reconstruction in patients with huge cranial-nasal communication defects. Bilateral reverse temporalis flaps provide reliable vascularization without microsurgery, and free flaps offer customizable volume. The reconstruction approach should be tailored to the defect size, donor site condition, and surgeon's expertise. (c) 2026 Published by Elsevier Ltd on behalf of British Association of Plastic, Reconstructive and Aesthetic Surgeons. 2026-05-01T00:00:00Z https://ir.ymlib.yonsei.ac.kr/handle/22282913/211615 Title: A prospective study for brain metastasis imaging screening in patients with advanced HER2-positive or triple-negative breast cancer Authors: Kim, G. M.; Kim, M. H.; Park, H. S.; Kim, J. H.; Kim, K. H.; Kim, S. -G.; Kim, J. Y.; Park, H, S.; Park, S.; Lee, S. -K.; Kim, Y. B.; Chang, J. H.; Kim, S. I.; Sohn, Joo Hyuk; 김건민; 김민환; 김지예; 박형석; 이승구; 김용배; 장종희; 김승일 Abstract: Background: Current guidelines for advanced breast cancer do not recommend routine brain imaging in neurologically asymptomatic patients. Prospective clinical evidence on the effectiveness of screening for early detection of brain metastasis (BM) remains limited. We conducted a prospective cohort study to evaluate the utility of magnetic resonance imaging (MRI) screening in patients with advanced human epidermal growth factor receptor 2-positive (HER2+) or triple-negative breast cancer (TNBC). Patients and methods: In this single-arm, prospective study, screening brain MRI was carried out at diagnosis in asymptomatic patients with advanced HER2+ or TNBC. Patients without BM on baseline MRI were monitored for the development of neurologic symptoms. Follow-up brain MRI studies were carried out at the initiation of second-and third-line systemic therapy. The primary endpoint was the detection rate of BM on screening MRI. Results: MRI detected asymptomatic BM in 11/112 (9.8%) patients at baseline; the cumulative detection rates increased to 17.0% and 19.6% by the initiation of second-and third-line therapy, respectively. Through this serial screening strategy, two-thirds of all BM cases (22/33) were identified at an asymptomatic stage. Patients with baseline metastatic involvement of three or more organ sites outside the central nervous system had an increased risk of BM (hazard ratio 3.38), and 38.5% of patients in this subgroup were diagnosed with BM by MRI screening. Stereotactic radiosurgery (66.7%) was the most common initial treatment for BM, and the median overall survival after BM diagnosis was 23.3 months. Conclusions: Two-thirds of BM cases in patients with advanced HER2+ or TNBC were diagnosed at an asymptomatic stage in this prospective serial brain MRI screening program. 2026-04-01T00:00:00Z