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ATP release mediated by TRPM3 enhances invasion in glioblastoma

2026-03-18T06:27:03Z

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.

Lesser occipital nerve decompression for medically refractory occipital headache: A retrospective case series

2026-06-12T07:52:32Z

Title: Lesser occipital nerve decompression for medically refractory occipital headache: A retrospective case series Authors: Ha, Jong-Ho; Park, Hyun Joo; Chung, Moonyoung; 하종호 Abstract: Background: Chronic intractable headaches significantly impair quality of life. Entrapment of the greater (GON) and lesser occipital nerves (LON) has been proposed as a potential cause of occipital headaches. While GON decompression has been widely studied, reports regarding the surgical technique and outcomes of LON decompression remain limited. This study aims to evaluate the clinical effectiveness of LON decompression in patients with medically refractory occipital headaches. Methods: A retrospective analysis was conducted on patients who underwent LOND between April 2021 and December 2024. Diagnostic C2 and/or C3 cervical blocks were used to support the clinical suspicion of occipital nerve-related headache with LON-predominant distribution. Pain was assessed using the Visual Analog Scale (VAS), Douleur Neuropathique 4 (DN4), and Neuropathic Pain Symptom Inventory (NPSI). Quality of life was measured using the SF-36. Operative details and relevant LON anatomical considerations are described.
Results: Nineteen patients were included in this study. Postoperatively, VAS scores decreased significantly (P < 0.001), with corresponding improvements in DN4 (P = 0.021) and NPSI (P <0.001) scores. SF-36 physical (P = 0.002) and mental component (P < 0.001) scores also improved notably. A longer duration of response to diagnostic blocks was associated with greater postoperative improvement in DN4 scores. No major complications were observed.
Conclusions: LON decompression may represent a safe and effective surgical option for selected patients with chronic occipital headaches refractory to conservative treatment, providing meaningful pain relief and improvements in quality of life. Larger, prospective studies are warranted to refine surgical indications and confirm long-term efficacy.

Low-dose radiation generated ROS-activatable doxorubicin prodrug loaded liposome nanoparticles for triple-negative breast cancer treatment

2026-03-25T06:50:21Z

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.

Analysis of skull base reconstruction methods in huge cranial-nasal communication defect: Bilateral reverse temporalis muscle flap and free flap

2026-04-29T08:21:42Z

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.