8521 Background: Combination chemotherapy of IMEP was active as a first-line as well as a second-line treatment for NTCL in a retrospective analysis. Thus, we conducted a prospective, multicenter, phase II study of IMEP chemotherapy in previously, untreated stage I/II NTCL. Methods: Patients with chemo-naïve stage I/II NTCL were enrolled between December 2004 and February 2009 and they received 6 cycles of IMEP (ifosfamide 1.5 g/m 2 on days 1 to 3; methotrextate 30mg/m 2 on days 3 and 10; etoposide 100mg/m 2 on days 1 to 3; and prednisolone 60mg/m 2 /day on days 1 to 5) followed by involved field radiotherapy (IFRT). Response was evaluated every 2 cycles of chemotherapy and 4 to 8 weeks after completion of IFRT using modified Response Evaluation Criteria in Solid Tumors. Results: Overall, 44 patients including 29 males were analyzed by the intent-to-treat principle. Overall response rates were 73% (complete remission [CR], 11 [27%] of 41 evaluable patients) after IMEP chemotherapy and 78% (CR, 18 [67%] of 27) after IMEP followed by IFRT. Grade 3 to 4 neutropenia and thrombocytopenia were documented in 33 (75%) and 7 (16%) patients, respectively. Only 8 (18%) patients experienced grade 3 febrile neutropenia. 2-year progression-free survival (PFS) and overall survival (OS) were 56% and 66%, respectively. High Ki-67 (≥ 70%) and Ann Arbor stage II independently reduced PFS (hazard ration [HR]=5.6, 95% confidence interval [CI] 1.8-17.6; P=.004) and OS (HR=4.8, 95% CI 1.9-12.2; P=.001), respectively. Conclusions: IMEP followed by IFRT is active and safe against patients with previously untreated stage I/II NTCL.

Patients with newly diagnosed, stages IE to IIE, nasal ENKTL are best treated with frontline CCRT.

Treatment with radiation alone had suboptimal results, partly because of the occurrence of a variety of systemic failure with diverse clinicopathologic features. Given the frequent occurrence of systemic failure after radiation treatment, we believe that the multimodality treatment approach containing more effective chemotherapeutic agents should be incorporated in the treatment of angiocentric lymphoma confined to the head and neck.

These findings suggest that machine learning models and individual acoustic features may not sufficiently capture treatment-related changes in MDD patients. This study underscores the value of deep learning models using the DVDSA method, addressing the limitations of pre- and post-treatment classification and highlighting their potential to advance personalized treatment strategies for adolescent MDD.

Vascular endothelial growth factor (VEGF) induces angiogenesis and vascular leakage by binding to cell surface receptor VEGFR2. KIF13B, a kinesin 3 family cellular motor, regulates VEGF/VEGFR2 signaling by bringing VEGFR2 to the cell surface. Regulating the trafficking of VEGFR2 could be a potential therapeutic target in pathogenesis originating from abnormal angiogenesis. However, the regulation mechanism of VEGFR2 trafficking is not fully understood. Here, we show that protein kinase D (PKD) phosphorylates KIF13B. The phosphorylation of KIF13B by PKD is required for KIF13B-VEGFR2 interaction and KIF13B-microtubule interaction. Live cell imaging using VEGFR2-mCherry revealed that the PKD inhibitor reduced the mean speed and total distance of VEGFR2 vesicular trafficking. Finally, inhibition of PKD also mitigated VEGF-induced permeability measured by trans-endothelial electrical resistance (TEER). Our results demonstrate how VEGFR2 trafficking is regulated by the phosphorylation of kinesin motor KIF13B by protein kinase PKD. We anticipate that elucidating the underlying mechanism of VEGFR2 trafficking can help progress the therapy development of the target diseases related to abnormal angiogenesis.

Background&Purpose: Polygenic risk scores (PRSs) for statin-induced low-density lipoprotein cholesterol (LDL-C) response have been developed in European cohorts, but their utility in non-European populations remains uncertain. We investigated the transferability of a European-derived LDL-C PRS to Korean patients with early-onset ischemic stroke. Methods: We analyzed 2,730 patients aged <55 years with acute ischemic stroke or transient ischemic attack (TIA) admitted within 7 days of onset to 17 academic or regional centers between 2017 and 2023 through the CRCS-K-NIH Registry. This cohort corresponds to the GENE_YAS (Genetic Analysis in Young Age Stroke Patients) study, a prospective sub-study of the CRCS-K-NIH designed to investigate genetic determinants of early-onset stroke. A PRS for on-statin LDL-C response was constructed using 35 single nucleotide polymorphisms identified in European cohorts. Follow-up LDL-C levels were measured 1–6 months post-stroke. Patients were stratified into PRS quartiles, and baseline characteristics, the absolute and percentage LDL-C reduction were compared. Multivariable logistic regression models estimated the association between PRS and treatment goals (LDL-C <70 mg/dL or ≥50% reduction), adjusting for age, sex, and atorvastatin-equivalent dose. Results: Mean age was 47.0 years, 72.4% were male, and baseline LDL-C was 119.3±40.5 mg/dL. Follow-up LDL-C decreased progressively across PRS quartiles (Q1: 81.4 mg/dL; Q2: 79.3 mg/dL; Q3: 75.4 mg/dL; Q4: 70.2 mg/dL; p<0.001). Percentage reduction increased from 27.5% in Q1 to 32.8% in Q4 (p=0.018). Absolute reduction ranged from 44.9 mg/dL in Q1 to 50.7 mg/dL in Q4 (p=0.021). Patients in the highest PRS quartile (Q4) had more than twofold greater odds of achieving LDL-C <70 mg/dL or ≥50% reduction compared with Q1 (adjusted OR 2.15, 95% CI 1.73–2.67, p<0.001). Each 1-SD increase in PRS corresponded to an additional 2.96 mg/dL LDL-C reduction (95% CI 1.37–4.55, p<0.001), independent of statin intensity. Discussion: A European-derived PRS for on-statin LDL-C response was significantly associated with both absolute and relative LDL-C reduction in young Korean stroke patients These findings support the cross-ancestry transferability of pharmacogenomic prediction tools and highlight their potential role in optimizing lipid-lowering strategies for secondary stroke prevention.

These findings suggest that the proposed multi-epitope vaccine represents a promising immunotherapeutic candidate for prostate cancer and warrants further experimental validation.

8521 Background: Combination chemotherapy of IMEP was active as a first-line as well as a second-line treatment for NTCL in a retrospective analysis. Thus, we conducted a prospective, multicenter, phase II study of IMEP chemotherapy in previously, untreated stage I/II NTCL. Methods: Patients with chemo-naïve stage I/II NTCL were enrolled between December 2004 and February 2009 and they received 6 cycles of IMEP (ifosfamide 1.5 g/m 2 on days 1 to 3; methotrextate 30mg/m 2 on days 3 and 10; etoposide 100mg/m 2 on days 1 to 3; and prednisolone 60mg/m 2 /day on days 1 to 5) followed by involved field radiotherapy (IFRT). Response was evaluated every 2 cycles of chemotherapy and 4 to 8 weeks after completion of IFRT using modified Response Evaluation Criteria in Solid Tumors. Results: Overall, 44 patients including 29 males were analyzed by the intent-to-treat principle. Overall response rates were 73% (complete remission [CR], 11 [27%] of 41 evaluable patients) after IMEP chemotherapy and 78% (CR, 18 [67%] of 27) after IMEP followed by IFRT. Grade 3 to 4 neutropenia and thrombocytopenia were documented in 33 (75%) and 7 (16%) patients, respectively. Only 8 (18%) patients experienced grade 3 febrile neutropenia. 2-year progression-free survival (PFS) and overall survival (OS) were 56% and 66%, respectively. High Ki-67 (≥ 70%) and Ann Arbor stage II independently reduced PFS (hazard ration [HR]=5.6, 95% confidence interval [CI] 1.8-17.6; P=.004) and OS (HR=4.8, 95% CI 1.9-12.2; P=.001), respectively. Conclusions: IMEP followed by IFRT is active and safe against patients with previously untreated stage I/II NTCL.

Patients with newly diagnosed, stages IE to IIE, nasal ENKTL are best treated with frontline CCRT.

Treatment with radiation alone had suboptimal results, partly because of the occurrence of a variety of systemic failure with diverse clinicopathologic features. Given the frequent occurrence of systemic failure after radiation treatment, we believe that the multimodality treatment approach containing more effective chemotherapeutic agents should be incorporated in the treatment of angiocentric lymphoma confined to the head and neck.