https://kumel.medlib.dsmc.or.kr/handle/2015.oak/29763 Thu, 19 Mar 2026 23:34:28 GMT 2026-03-19T23:34:28Z https://kumel.medlib.dsmc.or.kr/handle/2015.oak/46553 Title: Hepatitis B virus promotes liver cancer by modulating the immune response to environmental carcinogens Author(s): Mei Huang; Dongyao Wang; Jiao Huang; An-Na Bae; Yun Xia; Xutu Zhao; Mahsa Mortaja; Marjan Azin; Michael R Collier; Yevgeniy R Semenov; Jong Ho Park; Shadmehr Demehri Abstract: Hepatitis B virus (HBV) infection is associated with hepatitis and hepatocellular carcinoma (HCC). Considering that most HBV-infected individuals remain asymptomatic, the mechanism linking HBV to hepatitis and HCC remains uncertain. Herein, we demonstrate that HBV alone does not cause liver inflammation or cancer. Instead, HBV alters the chronic inflammation induced by chemical carcinogens to promote liver carcinogenesis. Long-term HBV genome expression in mouse liver increases liver inflammation and cancer propensity caused by a carcinogen, diethylnitrosamine (DEN). HBV plus DEN-activated interleukin-33 (IL-33)/regulatory T cell axis is required for liver carcinogenesis. Pitavastatin, an IL-33 inhibitor, suppresses HBV plus DEN-induced liver cancer. IL-33 is markedly elevated in HBV+ hepatitis patients, and pitavastatin use significantly correlates with reduced risk of hepatitis and its associated HCC in patients. Collectively, our findings reveal that environmental carcinogens are the link between HBV and HCC risk, creating a window of opportunity for cancer prevention in HBV carriers. Tue, 31 Dec 2024 15:00:00 GMT https://kumel.medlib.dsmc.or.kr/handle/2015.oak/46553 2024-12-31T15:00:00Z https://kumel.medlib.dsmc.or.kr/handle/2015.oak/46519 Title: Design of cathepsin-sensitive linkers for tumor-selective bioconjugate drug delivery Author(s): Anil Giri; Yulim Shin; Jin Ha; Siyeon Chae; Prabhat Shrestha; Khang-Yen Pham; Taeg Kyu Kwon; Jong Ho Park; Jee-Heon Jeong; Na Kyeong Lee; Simmyung Yook Abstract: Cysteine cathepsin, particularly cathepsin B, have emerged as pivotal enzymatic targets in the design of drug delivery systems owing to their overexpression in diverse pathological conditions, most notably cancer. This review provides a comprehensive overview of cathepsin B-cleavable linkers, emphasizing their role in current bioconjugate design and their application across multiple therapeutic platforms. It also provides a comparative overview of linker engineering guided by cathepsin B, ranging from simple dipeptides constructs to modified peptide linkers. These structural refinements are correlated with improvements in substrate discrimination, stability, and cleavage efficiency. Substantial attention is provided to three primary bioconjugate platforms: antibody-drug conjugates (ADCs), prodrug systems and nanoparticle conjugates. Each section enumerates the corresponding unique design, conjugation chemistry, payload distribution modalities, and progress in regulatory translation. The parallel evaluation supports that, while collectively successful, ADCs have yielded the most mature clinical outcomes, notwithstanding ongoing refinements that promise to widen the therapeutic index of prodrug and nanoparticle platforms. Key challenges include achieving a balance between linker stability in circulation and efficient cleavage at the target site, minimizing off-target activation, and accounting for variability in cathepsin expression among patients. Future direction focusses on both advancing linker technology through enhanced stability, refined pharmacokinetics, and multi-mechanism combination strategies and implementing patient stratification for clinical relevance. Tue, 31 Dec 2024 15:00:00 GMT https://kumel.medlib.dsmc.or.kr/handle/2015.oak/46519 2024-12-31T15:00:00Z https://kumel.medlib.dsmc.or.kr/handle/2015.oak/46497 Title: ElF5B as a prognostic biomarker and its correlation with infiltrating immune cells in liver cancer Author(s): Tae-Young Kim; An-Na Bae; Jae-Ho Lee Abstract: Background and objectives: The clinical behavior and molecular mechanisms of hepatocellular carcinoma (HCC) are intricate and highly variable, posing challenges for identifying novel targets in clinical research. The gene eukaryotic translation initiation factors 5B (EIF5B) plays a role in synthesize translation initiation complexes during the synthesis of eukaryotic proteins. Materials and methods: We conducted a comprehensive bioinformatics analysis using public databases including Tumor Immune Estimation Resource (TIMER), UALCAN, Kaplan-Meier plotter, LinkedOmics, and Gene Expression Profiling Interactive Analysis (GEPIA2). Results: EIF5B expression in HCC samples was significantly higher than in normal liver tissue; additionally, EIF5B was highly in primary tumors, various stages of cancer and grades of tumor, and status of nodal metastasis. Higher EIF5B expression was also associated with diagnosis. EIF5B expression showed a positive correlation with B cells macrophages, myeloid dendritic cells, neutrophils, and CD4+ T cells. In the analysis of EIF5B co-expression networks, positively related genes of EIF5B were associated with a high hazard ration in different types of cancer, including HCC. In biological function of EIF5B, mainly plays including protein localization to chromosome, rRNA metabolic process, and ncRNA processing, etc. Conclusion: These results suggest that EIF5B may serve as a novel biomarker with prognostic relevance in HCC and provide insights into tumor immunology in HCC. Tue, 31 Dec 2024 15:00:00 GMT https://kumel.medlib.dsmc.or.kr/handle/2015.oak/46497 2024-12-31T15:00:00Z https://kumel.medlib.dsmc.or.kr/handle/2015.oak/46445 Title: Clinical and Prognostic Value of TIMP1 in Colorectal Cancer Author(s): Jaeho Lee; Leejune chai; Yujoon Cha; Hyeok-Jun Moon Abstract: Tissue inhibitor of metalloproteinases 1 (TIMP1) is a multifunctional molecule that acts as the primary endogenous inhibitors of metalloproteinases (MPs). The imbalance between MMPs and TIMPs can lead to various cancers. We aim to prove the clinical and prognostic value of TIMP1 gene in colorectal cancer (CRC). Materials and Methods: TIMP1 mRNA expression was examined in various cancer types. We further evaluated survival to determine the prognostic significance of TIMP1 mRNA in CRC using The Cancer Genome Atlas (TCGA) data. Results: The patients were divided into two subgroups, based on the TIMP1 gene expression levels to assess the clinical characteristics associated with TIMP1 expression. In rectal cancer, higher TIMP1 expression was linked to venous invasion, and there was also a correlated with histological type, location, and MSI types in colon cancer. Survival analysis showed that higher TIMP1 group was statistically associated with poorer prognosis. Our findings suggest that elevated TIMP1 mRNA expression is significantly associated with aggressive clinicopathological features and poor prognosis in CRC. TIMP1 may serve as a potential biomarker for risk stratification and a therapeutic target in CRC management. Tue, 31 Dec 2024 15:00:00 GMT https://kumel.medlib.dsmc.or.kr/handle/2015.oak/46445 2024-12-31T15:00:00Z