https://scholar.dgist.ac.kr/handle/20.500.11750/329 2026-06-11T02:14:32Z https://scholar.dgist.ac.kr/handle/20.500.11750/60409 Title: Deciphering the Heterogeneity of Cancer-Associated Fibroblasts in Prostate Cancer: From Stromal Biology to Clinical Translation Author(s): Truong, Ho Trong Tan; Kwon, Whi-An; Woo, Hyeong Jung; Kim, Minseok S.; Tran, Nhu Quang; Joung, Jae Young Abstract: Prostate cancer (PCa) progression and treatment resistance are driven by tumor-intrinsic mechanisms and adaptive remodeling of the tumor microenvironment, in which cancer-associated fibroblasts (CAFs) play a crucial role. Although CAF biology is increasingly recognized, a major translational gap remains: CAFs are highly heterogeneous, and comprise distinct functional states with divergent effects on disease progression, immune regulation, and therapeutic resistance. To bridge this gap, we synthesize evidence from single-cell and spatial transcriptomic studies, tissue-based pathology, liquid biopsy assays, and molecular imaging to construct an evidence-tiered, decision-oriented translational framework that connects stromal mechanisms, translational measurement strategies, and therapeutic interventions in PCa. Single-cell and spatial transcriptomic analyses have consistently identified multiple CAF programs, including matrix-remodeling, inflammatory, immunoregulatory, antigen-presenting, and therapy-imprinted states, each with distinct functional outputs and clinical correlates. Tissue-based readouts, including reactive stromal grade (RSG) and fibroblast activation protein (FAP) immunohistochemistry, provide practical proxies for stromal activation and correlate with disease-specific mortality and imaging phenotypes. Circulating CAFs (cCAFs) represent an emerging liquid biopsy modality for longitudinal stromal monitoring, although technical standardization is required before clinical implementation. FAP-targeted PET imaging and emerging dual prostate-specific membrane antigen (PSMA)/FAP-targeted theranostic strategies provide noninvasive tools for patient selection and response assessment, particularly in PSMA-discordant or tracer-heterogeneous disease. Androgen receptor (AR)-targeted therapy can reprogram stromal states toward resistance-promoting circuits, highlighting the dynamic and plastic nature of the CAF compartment. A state-based CAF framework organizes stromal biology into testable translational hypotheses rather than immediate clinical standards. RSG and FAP-based tissue or imaging readouts are practical markers of stromal activation, whereas spatial CAF-immune signatures and cCAF assays remain investigational and require assay harmonization and prospective validation. Future trials should pre-specify stromal biomarkers as enrichment or pharmacodynamic variables when matched to the intervention and should avoid treating CAFs as a uniform therapeutic target. 2026-04-30T15:00:00Z https://scholar.dgist.ac.kr/handle/20.500.11750/60388 Title: Modulation of WNT and FGF18 enhances yield and subtype identity of hPSC-derived midbrain dopamine neurons Author(s): Kim, Tae Wan; Piao, Jinghua; Bocchi, Vittoria D.; Koo, So Yeon; Choi, Se Joon; Chaudhry, Fayzan; Yang, Donghe; Cho, Hyein S.; Hergenreder, Emiliano; Ruiz Perera, Lucia; Joshi, Subhashini; Abou Mrad, Zaki; Claros, Nidia; Donohue, Shkurte Ademi; Eun Im, Yeong; Jeong, Hyo Jae; Frank, Anika K.; Walsh, Ryan M.; Mosharov, Eugene V.; Betel, Doron; Tabar, Viviane; Studer, Lorenz Abstract: While clinical trials of human pluripotent stem cell-derived midbrain dopamine (mDA) neuron precursor grafts for Parkinson's disease (PD) are ongoing, current protocols remain suboptimal. In particular, the yield of TH+ mDA neurons after in vivo grafting and the expression of certain mDA neuron and subtype-specific markers require improvement. Single-cell transcriptomic analyses of grafts have revealed low proportions of mDA neurons and substantial off-target contamination. Here, we present an optimized mDA neuron differentiation strategy that builds on our clinical-grade ("Boost") protocol by adding FGF18 and IWP2 treatment ("Boost+") at the neurogenesis stage. Boost+ mDA neurons show higher expression of EN1, PITX3, and ALDH1A1. Improvements in mDA neuron yield and transcriptional similarity to primary mDA neurons are observed in vitro and following transplantation. Single-nucleus RNA sequencing demonstrates enrichment of A9 mDA neurons within Boost+ grafts. Functional studies in vitro demonstrate increased dopamine production and release and improved electrophysiological properties. In vivo analyses show higher percentages of TH+ mDA neurons, resulting in efficient rescue of amphetamine-induced rotation behavior in the 6-OHDA rat model and rescue of deficits in some nondrug-induced assays, including the ladder rung assay, which are not improved by Boost mDA neurons. The Boost+ conditions present an optimized differentiation protocol with advantages for disease modeling and mDA neuron grafting paradigms. 2026-04-30T15:00:00Z https://scholar.dgist.ac.kr/handle/20.500.11750/60382 Title: 전자약의 스크리닝 장치 및 이를 이용한 스크리닝 방법 Author(s): 김운해; 김민석; 강현규 https://scholar.dgist.ac.kr/handle/20.500.11750/60372 Title: 면역 항암 활성 사이토카인을 스크리닝하는 방법 및 IL-15를 유효성분으로 포함하는 암 질환 예방 또는 치료용 조성물 Author(s): 강성민; 예경무; 백문창 Abstract: 본 발명은 암세포의 엑소좀 분비를 억제하거나 프로그램된 세포사멸-리간드의 발현을 억제하는 면역 항암 활성을 갖는 사이토카인을 스크리닝 하는 방법에 관한 것으로, 사이토카인을 암호화하는 유전자, 링커를 암호화하는 링커 도메인, 및 막관통 단백질을 암호화하는 막관통 도메인으로 구성된 벡터를 암세포에 형질전환함으로써, 엑소좀 분비와 관련된 유전자의 발현 수준 또는 PD-L1의 발현 수준을 억제하는 면역 항암 활성을 나타내는 사이토카인을 선별할 수 있으며, 선별된 사이토카인을 새로운 항암제로 제공한다. 또한, 본 발명은 위의 스크리닝 기법을 이용하여 선별한 IL-15, 이의 발현 촉진제 또는 활성화제를 유효성분으로 포함하는 암 질환 예방 또는 치료용 조성물에 관한 것으로, 본 발명에서는 암세포에 IL-15를 처리 시, 암세포 유래 엑소좀 분비가 억제되고, T 세포의 면역 회피를 유도하는 PD-L1의 발현이 억제되어 항암 효과가 증진되는 것을 확인하였으며, 암세포에 직접적으로 항암 효과를 나타내는 것을 확인하였다. IL-15가 세포독성 T 세포를 활성화시키고 면역관문 PD-1, CTLA-4를 감소시키며 면역세포 유래 엑소좀을 증진시켜 면역 항암 효과를 나타내는 것을 확인하였다. 이는 IL-15, 이의 발현 촉진제 또는 활성화제는 암 질환 예방 또는 치료용 조성물 등으로 유용하게 활용될 수 있다.