Purpose: Human epidermal growth factor receptor 2 (HER2) is amplified or overexpressed in various malignancies, including breast and gastric cancers, and is associated with poor prognosis. Although HER2-targeted therapies, such as trastuzumab, improve outcomes in HER2-positive tumors, resistance often develops, and HER2-low tumors remain largely untargeted. Trastuzumab deruxtecan (T-DXd; DS-8201a) is a HER2-targeted antibody-drug conjugate with potent activity in HER2-positive and HER2-low tumors. This study evaluates its antitumor mechanisms and efficacy in HER2-positive, HER2-low, and homologous recombination deficiency (HRD)–associated models. Materials and Methods: Effects of T-DXd were assessed in cancer cell lines with diverse HER2 expression and HRD status. In vivo efficacy was evaluated using a xenograft model derived from HER2-low SNU-601 gastric cancer cells. Results: T-DXd reduced HER2 phosphorylation and downstream signaling (AKT, ERK) in HER2-positive cells. It induced DNA damage accumulation, as evidenced by increased γH2AX and p-Chk1 expression, and triggered apoptosis through cleaved poly(ADP-ribose) polymerase and caspase-3 activation, confirmed by annexin V staining. Similar effects were observed in HER2-low cells, with greater sensitivity in HRD cells. In xenografts, T-DXd reduced tumor volume by up to 80% at 4 mg/kg and 10 mg/kg. Histological analyses showed decreased Ki-67 and increased apoptosis. Furthermore, T-DXd induced G2/M cell cycle arrest and nuclear anaplasia, suggesting disruption of chromosomal stability as a potential antitumor mechanism. No significant toxicity, including body weight loss, was observed. Conclusion These findings highlight T-DXd’s effectiveness in HER2-low and HRD tumors, supporting its broader clinical application, including strategies targeting DNA damage repair pathways.

Purpose: Sustained cell proliferation and cell cycle acceleration in cancer cells inherently increase DNA damage, which interferes with homeostatic replication and transcription. Ataxia telangiectasia and Rad3-related (ATR) is crucial for initiation of the DNA damage response, and ATR inhibitors, such as elimusertib, induce increased replication stress and DNA damage. We investigated the anti-tumor effects of elimusertib and its mechanism of action in relation to replication stress. Materials and Methods: Anti-tumor effects were evaluated by MTT assay and colony formation assay in breast cancer cell lines in vitro, in breast cancer cell xenografts in vivo, and in patient-derived xenograft models. Cell cycle was assessed by flow cytometry and BrdU assay was used to measure replicating cells and S-phase progression. Alkaline and neutral comet assay was used to measure single and double-stranded DNA damages, respectively. Results: Elimusertib delayed S-phase progression in MDA-MB-453 and MDA-MB-231 cells and induced caspase-7–dependent apoptosis. Furthermore, the increase in sub-G1 population in the fluorescence-activated cell sorting analysis and Annexin V assay also confirmed apoptotic cell death. In the BrdU assay, single-stranded DNA (ssDNA) increased in sensitive cells and aberrant ssDNA induced DNA damage in S-phase and eventually caused replication catastrophe. Finally, these anti-tumor effects were proven in in vivo xenograft and patient-derived xenograft models. Conclusion Elimusertib had anti-tumor effects and induced replication catastrophe in breast cancer cells with a high replication rate. Moreover, cells under high DNA replication stress were sensitive to elimusertib. Further studies and treatment strategies with elimusertib are warranted for cancers with a high replication rate.

Blood cancers, including leukemia, multiple myeloma, and lymphoma, pose significant challenges owing to their heterogeneous nature and the limitations of traditional treatments. Precision medicine has emerged as a transformative approach that offers tailored therapeutic strategies based on individual patient profiles. Ex vivo drug sensitivity analysis is central to this advancement, which enables testing of patient-derived cancer cells against a panel of therapeutic agents to predict clinical responses. This review provides a comprehensive overview of the latest advancements in ex vivo drug sensitivity analyses and their application in blood cancers. We discuss the development of more comprehensive drug response metrics and the evaluation of drug combinations to identify synergistic interactions.Additionally, we present evaluation of the advanced therapeutics such as antibody–drug conjugates using ex vivo assays. This review describes the critical role of ex vivo drug sensitivity analyses in advancing precision medicine by examining technological innovations and clinical applications. Ultimately, these innovations are paving the way for more effective and individualized treatments, improving patient outcomes, and establishing new standards for the management of blood cancers.

Blood cancers, including leukemia, multiple myeloma, and lymphoma, pose significant challenges owing to their heterogeneous nature and the limitations of traditional treatments. Precision medicine has emerged as a transformative approach that offers tailored therapeutic strategies based on individual patient profiles. Ex vivo drug sensitivity analysis is central to this advancement, which enables testing of patient-derived cancer cells against a panel of therapeutic agents to predict clinical responses. This review provides a comprehensive overview of the latest advancements in ex vivo drug sensitivity analyses and their application in blood cancers. We discuss the development of more comprehensive drug response metrics and the evaluation of drug combinations to identify synergistic interactions.Additionally, we present evaluation of the advanced therapeutics such as antibody–drug conjugates using ex vivo assays. This review describes the critical role of ex vivo drug sensitivity analyses in advancing precision medicine by examining technological innovations and clinical applications. Ultimately, these innovations are paving the way for more effective and individualized treatments, improving patient outcomes, and establishing new standards for the management of blood cancers.

Blood cancers, including leukemia, multiple myeloma, and lymphoma, pose significant challenges owing to their heterogeneous nature and the limitations of traditional treatments. Precision medicine has emerged as a transformative approach that offers tailored therapeutic strategies based on individual patient profiles. Ex vivo drug sensitivity analysis is central to this advancement, which enables testing of patient-derived cancer cells against a panel of therapeutic agents to predict clinical responses. This review provides a comprehensive overview of the latest advancements in ex vivo drug sensitivity analyses and their application in blood cancers. We discuss the development of more comprehensive drug response metrics and the evaluation of drug combinations to identify synergistic interactions.Additionally, we present evaluation of the advanced therapeutics such as antibody–drug conjugates using ex vivo assays. This review describes the critical role of ex vivo drug sensitivity analyses in advancing precision medicine by examining technological innovations and clinical applications. Ultimately, these innovations are paving the way for more effective and individualized treatments, improving patient outcomes, and establishing new standards for the management of blood cancers.

Abstinence from prolonged psychostimulant use prompts stimulant withdrawal syndrome. Molecular adaptations within the dorsal striatum have been considered the main hallmark of stimulant abstinence. Here we explored striatal miRNA-target interaction and its impact on circulating miRNA marker as well as behavioral dysfunctions in methamphetamine (MA) abstinence. We conducted miRNA sequencing and profiling in the nonhuman primate model of MA abstinence, followed by miRNA qPCR, LC-MS/MS proteomics, immunoassays, and behavior tests in mice. In nonhuman primates, MA abstinence triggered a lasting upregulation of miR-137 in the dorsal striatum but a simultaneous downregulation of circulating miR-137. In mice, aberrant increase in striatal miR-137-dependent inhibition of SYNCRIP essentially mediated the MA abstinence-induced reduction of circulating miR-137. Pathway modeling through experimental deduction illustrated that the MA abstinence-mediated downregulation of circulating miR-137 was caused by reduction of SYNCRIP-dependent miRNA sorting into the exosomes in the dorsal striatum. Furthermore, diminished SYNCRIP in the dorsal striatum was necessary for MA abstinence-induced behavioral bias towards egocentric spatial learning. Taken together, our data revealed circulating miR-137 as a potential blood-based marker that could reflect MA abstinence-dependent changes in striatal miR-137/SYNCRIP axis, and striatal SYNCRIP as a potential therapeutic target for striatum-associated cognitive dysfunction by MA withdrawal syndrome.

Omija berry (Schisandra fructus) is a traditional Korean fruit, which contains lots of medicinal ingredients. In order to analyze whether Omija contains antibacterial components, we extracted Omija using five different methods including water precipitation, ethanol precipitation, hot water extract, methanol-ultrasonication, and water-ultrasonication, and examined their antimicrobial activities against Escherichia coli (E. coli), and Bacillus cereus (B. cereus). Most of Omija extracts did not inhibit bacteria growth in the paper disc diffusion assay except hot water extract for 60 minutes. Hot water extract for 60 minutes made clear inhibition zone around the disc at all the concentrations (x1, x1/10, x1/100) in both E. coli and B. cereus. However, hot water extracts for 90 minutes and 120 minutes showed antimicrobial activities only at x1 stock solution, which indicates that 60 minutes extraction at hot water is the best method to obtain Omija extract with the best antimicrobial activities in disc diffusion assay. In turbidimetric assay, water extract in soak, hot water extract, and methanol extract in ultrasonicator inhibited growth of both E. coli and B. cereus. Ethanol extract in soak and water extract in ultrasonicator had no effect on bacterial growth in both E. coli and B. cereus. In this study, we found that Omija extracts showed antimicrobial activities against E. coli and B. cereus. Therefore, water soluble materials of Omija can be used as a drink supplement and developed as an antibacterial cleanser.
Bacillus cereus* ; Bacillus* ; Bacteria ; Diffusion ; Escherichia coli ; Ethanol ; Fruit ; Methanol ; Methods ; Water