Background: Kelch-like ECH-associated protein 1 (KEAP1)–nuclear factor erythroid- 2-related factor 2 (NRF2) pathway is a major regulator protecting cells from oxidative and metabolic stress. Studies have revealed that this pathway is involved in mediating resistance to cytotoxic chemotherapy and immunotherapy; however, its implications in oncogene-addicted tumors are largely unknown. This study aimed to elucidate whether this pathway could be a potential therapeutic target for epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer. Methods: We measured the baseline expression of NRF2 using EGFR-mutant parental cells and acquired gefitinib resistant cells. We investigated whether NRF2 inhibition affected cell death in vitro and tumor growth in vivo using a xenograft mouse model, and compared the transcriptional changes before and after NRF2 inhibition. Results: Baseline NRF2 expression was enhanced in PC9 and PC9 with gefitinib resistance (PC9/GR) cells than in other cell lines, with a more prominent expression in PC9/ GR. The NRF2 inhibitor induced NRF2 downregulation and cell death in a dose-dependent manner. Cotreatment with an NRF2 inhibitor enhanced osimertinib-induced cell death in vitro, and potentiated tumor growth inhibition in a PC9/GR xenograft model. Finally, RNA sequencing revealed that NRF2 inhibition resulted in the altered expression of multiple genes involved in various signaling pathways. Conclusion We identified that NRF2 inhibition enhanced cell death and inhibited tumor growth in tyrosine kinase inhibitor (TKI)-resistant lung cancer with EGFR-mutation. Thus, NRF2 modulation may be a novel therapeutic strategy to overcome the resistance to EGFR-TKIs.

Background: Kelch-like ECH-associated protein 1 (KEAP1)–nuclear factor erythroid- 2-related factor 2 (NRF2) pathway is a major regulator protecting cells from oxidative and metabolic stress. Studies have revealed that this pathway is involved in mediating resistance to cytotoxic chemotherapy and immunotherapy; however, its implications in oncogene-addicted tumors are largely unknown. This study aimed to elucidate whether this pathway could be a potential therapeutic target for epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer. Methods: We measured the baseline expression of NRF2 using EGFR-mutant parental cells and acquired gefitinib resistant cells. We investigated whether NRF2 inhibition affected cell death in vitro and tumor growth in vivo using a xenograft mouse model, and compared the transcriptional changes before and after NRF2 inhibition. Results: Baseline NRF2 expression was enhanced in PC9 and PC9 with gefitinib resistance (PC9/GR) cells than in other cell lines, with a more prominent expression in PC9/ GR. The NRF2 inhibitor induced NRF2 downregulation and cell death in a dose-dependent manner. Cotreatment with an NRF2 inhibitor enhanced osimertinib-induced cell death in vitro, and potentiated tumor growth inhibition in a PC9/GR xenograft model. Finally, RNA sequencing revealed that NRF2 inhibition resulted in the altered expression of multiple genes involved in various signaling pathways. Conclusion We identified that NRF2 inhibition enhanced cell death and inhibited tumor growth in tyrosine kinase inhibitor (TKI)-resistant lung cancer with EGFR-mutation. Thus, NRF2 modulation may be a novel therapeutic strategy to overcome the resistance to EGFR-TKIs.

Background: Kelch-like ECH-associated protein 1 (KEAP1)–nuclear factor erythroid- 2-related factor 2 (NRF2) pathway is a major regulator protecting cells from oxidative and metabolic stress. Studies have revealed that this pathway is involved in mediating resistance to cytotoxic chemotherapy and immunotherapy; however, its implications in oncogene-addicted tumors are largely unknown. This study aimed to elucidate whether this pathway could be a potential therapeutic target for epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer. Methods: We measured the baseline expression of NRF2 using EGFR-mutant parental cells and acquired gefitinib resistant cells. We investigated whether NRF2 inhibition affected cell death in vitro and tumor growth in vivo using a xenograft mouse model, and compared the transcriptional changes before and after NRF2 inhibition. Results: Baseline NRF2 expression was enhanced in PC9 and PC9 with gefitinib resistance (PC9/GR) cells than in other cell lines, with a more prominent expression in PC9/ GR. The NRF2 inhibitor induced NRF2 downregulation and cell death in a dose-dependent manner. Cotreatment with an NRF2 inhibitor enhanced osimertinib-induced cell death in vitro, and potentiated tumor growth inhibition in a PC9/GR xenograft model. Finally, RNA sequencing revealed that NRF2 inhibition resulted in the altered expression of multiple genes involved in various signaling pathways. Conclusion We identified that NRF2 inhibition enhanced cell death and inhibited tumor growth in tyrosine kinase inhibitor (TKI)-resistant lung cancer with EGFR-mutation. Thus, NRF2 modulation may be a novel therapeutic strategy to overcome the resistance to EGFR-TKIs.

Background: Kelch-like ECH-associated protein 1 (KEAP1)–nuclear factor erythroid- 2-related factor 2 (NRF2) pathway is a major regulator protecting cells from oxidative and metabolic stress. Studies have revealed that this pathway is involved in mediating resistance to cytotoxic chemotherapy and immunotherapy; however, its implications in oncogene-addicted tumors are largely unknown. This study aimed to elucidate whether this pathway could be a potential therapeutic target for epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer. Methods: We measured the baseline expression of NRF2 using EGFR-mutant parental cells and acquired gefitinib resistant cells. We investigated whether NRF2 inhibition affected cell death in vitro and tumor growth in vivo using a xenograft mouse model, and compared the transcriptional changes before and after NRF2 inhibition. Results: Baseline NRF2 expression was enhanced in PC9 and PC9 with gefitinib resistance (PC9/GR) cells than in other cell lines, with a more prominent expression in PC9/ GR. The NRF2 inhibitor induced NRF2 downregulation and cell death in a dose-dependent manner. Cotreatment with an NRF2 inhibitor enhanced osimertinib-induced cell death in vitro, and potentiated tumor growth inhibition in a PC9/GR xenograft model. Finally, RNA sequencing revealed that NRF2 inhibition resulted in the altered expression of multiple genes involved in various signaling pathways. Conclusion We identified that NRF2 inhibition enhanced cell death and inhibited tumor growth in tyrosine kinase inhibitor (TKI)-resistant lung cancer with EGFR-mutation. Thus, NRF2 modulation may be a novel therapeutic strategy to overcome the resistance to EGFR-TKIs.

Background: Kelch-like ECH-associated protein 1 (KEAP1)–nuclear factor erythroid- 2-related factor 2 (NRF2) pathway is a major regulator protecting cells from oxidative and metabolic stress. Studies have revealed that this pathway is involved in mediating resistance to cytotoxic chemotherapy and immunotherapy; however, its implications in oncogene-addicted tumors are largely unknown. This study aimed to elucidate whether this pathway could be a potential therapeutic target for epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer. Methods: We measured the baseline expression of NRF2 using EGFR-mutant parental cells and acquired gefitinib resistant cells. We investigated whether NRF2 inhibition affected cell death in vitro and tumor growth in vivo using a xenograft mouse model, and compared the transcriptional changes before and after NRF2 inhibition. Results: Baseline NRF2 expression was enhanced in PC9 and PC9 with gefitinib resistance (PC9/GR) cells than in other cell lines, with a more prominent expression in PC9/ GR. The NRF2 inhibitor induced NRF2 downregulation and cell death in a dose-dependent manner. Cotreatment with an NRF2 inhibitor enhanced osimertinib-induced cell death in vitro, and potentiated tumor growth inhibition in a PC9/GR xenograft model. Finally, RNA sequencing revealed that NRF2 inhibition resulted in the altered expression of multiple genes involved in various signaling pathways. Conclusion We identified that NRF2 inhibition enhanced cell death and inhibited tumor growth in tyrosine kinase inhibitor (TKI)-resistant lung cancer with EGFR-mutation. Thus, NRF2 modulation may be a novel therapeutic strategy to overcome the resistance to EGFR-TKIs.

Methods: Magnetic resonance imaging (MRI) and clinical evaluation were performed for patients with single-level uniportal endoscopic lumbar decompression with a minimum follow-up of 2 years. Results: A total of 126 patients were recruited with a minimum follow-up of 26 months. The incidence of epidural fluid hematoma was 27%. Postoperative MRI revealed a significant improvement in the postoperative dura sac area at postoperative day 1 and at the upper endplate at 6 months in the hematoma cohort (39.69±15.72 and 26.89±16.58 mm2) as compared with the nonhematoma cohort (48.92±21.36 and 35.1±20.44 mm2), respectively (p <0.05); and at the lower endplate on postoperative 1 day in the hematoma cohort (51.18±24.69 mm2) compared to the nonhematoma cohort (63.91±27.92 mm2) (p <0.05). No significant difference was observed in the dura sac area at postoperative 1 year in both cohorts. The hematoma cohort had statistically significant higher postoperative 1-week Visual Analog Scale (VAS; 3.32±0.68) pain and Oswestry Disability Index (ODI; 32.65±5.56) scores than the nonhematoma cohort (2.99±0.50 and 30.02±4.84, respectively; p <0.05). No significant difference was found at the final follow-up VAS, ODI, and MRI dura sac area. Conclusions Epidural fluid hematoma is a common early postoperative MRI finding in lumbar endoscopic unilateral laminotomy with bilateral decompression. Conservative management is the preferred treatment option for patients who do not have a neurological deficit. Symptoms last only a few days and are self-limiting. A common endpoint is a remodeled fluid hematoma and the subsequent expansion of the dura sac area.

Purpose: Although osimertinib is the standard-of-care treatment of epidermal growth factor receptor (EGFR) T790M mutation–positive non–small cell lung cancer, real-world evidence on the efficacy of osimertinib is not enough to reflect the complexity of the entire course of treatment. Herein, we report on the use of osimertinib in patients with EGFR T790M mutation–positive non–small cell lung cancer who had previously received EGFR tyrosine kinase inhibitor (TKI) treatment in Korea. Materials and Methods: Patients with confirmed EGFR T790M after disease progression of prior EGFR-TKI were enrolled and administered osimertinib 80 mg daily. The primary effectiveness outcome was progression-free survival, with time-to-treatment discontinuation, treatment and adverse effects leading to treatment discontinuation, and overall survival being the secondary endpoints. Results: A total of 558 individuals were enrolled, and 55.2% had investigator-assessed responses. The median progression-free survival was 14.2 months (95% confidence interval [CI], 13.0 to 16.4), and the median time-to-treatment discontinuation was 15.0 months (95% CI, 14.1 to 15.9). The median overall survival was 36.7 months (95% CI, 30.9 to not reached). The benefit with osimertinib was consistent regardless of the age, sex, smoking history, and primary EGFR mutation subtype. However, hepatic metastases at the time of diagnosis, the presence of plasma EGFR T790M, and the shorter duration of prior EGFR-TKI treatment were poor predictors of osimertinib treatment. Ten patients (1.8%), including three with pneumonitis, had to discontinue osimertinib due to severe adverse effects. Conclusion Osimertinib demonstrated its clinical effectiveness and survival benefit for EGFR T790M mutation–positive in Korean patients with no new safety signals.

Methods: We evaluated patients who underwent EPTLIF with a minimum 24-month follow-up. Clinical parameters of the Visual Analog Scale (VAS) and Oswestry Disability Index (ODI) were measured at the preoperative, 1-week postoperative mark, postoperative 3-month mark, and final follow-up. Preoperative and 1-year postoperative magnetic resonance imaging measurement of preoperative and postoperative Kjaer grade, right and left psoas muscle mass area, and right and left paraspinal muscle mass area was performed. Results: EPTLIF with a minimum 24-month follow-up of 35 levels was included. The complication rate was 6%, and the mean Bridwell’s fusion grade was 1.37 (1–2). There was statistically significant improvement at 1 week, 3 months, and 2 years in VAS (4.11±1.23, 4.94±1.30, and 5.46±1.29) and in ODI (40.34±10.06, 46.69±9.14, and 49.63±8.68), respectively (p <0.05). Successful operation rate with excellent and good MacNab’s criteria at 2 years was 97%. There was an increment of statistically significant bilateral psoas muscle cross-sectional area, right side (70.03±149.1 mm²) and left side (67.59±113.2 mm²) (p <0.05). Conclusions Uniportal EPTLIF achieved good fusion and improved clinical outcomes with favorable paraspinal musculature bulk at the 2-year follow-up.

Objective: : Stent-assisted coil embolization (SAC) has been increasingly used to treat various types of intracranial aneurysms. Delayed thromboembolic complications are major concerns regarding this procedure, so dual antiplatelet therapy with aspirin and clopidogrel is needed. However, clinicians vary the duration of dual antiplatelet therapy after SAC, and no randomized study has been performed. This study aims to compare the safety and efficacy of long-term (12 months) dual antiplatelet therapy and shortterm dual antiplatelet therapy (6 months) after SAC for patients with unruptured intracranial aneurysms (UIAs). Methods: : This is a prospective, randomized and multicenter trial to investigate the optimal duration of dual antiplatelet therapy after SAC in patients with UIAs. Subjects will receive dual antiplatelet therapy for 6 months (short-term group) or 12 months (longterm group) after SAC. The primary endpoint is the assessment of thromboembolic complications between 1 and 18 months after SAC. We will enroll 528 subjects (264 subjects in each group) and perform 1 : 1 randomization. This study will involve 14 topperforming, high-volume Korean institutions specializing in coil embolization. Results: : The trial will begin enrollment in 2022, and clinical data will be available after enrollment and follow-up. Conclusion : This article describes that the aim of this prospective randomized multicenter trial is to compare the effect of short-term (6 months) and long-term (12 months) dual antiplatelet therapy on UIAs in patients undergoing SAC, and to find the optimal duration.

In cancer genome studies, the annotation of newly detected oncogene/tumor suppressor gene candidates is a challenging process. We propose using concept lattice analysis for the annotation and interpretation of genes having candidate somatic mutations in whole-exome sequencing in acute myeloid leukemia (AML). We selected 45 highly mutated genes with whole-exome sequencing in 10 normal matched samples of the AML-M2 subtype. To evaluate these genes, we performed concept lattice analysis and annotated these genes with existing knowledge databases.
DNA Mutational Analysis ; Genes, Suppressor ; Genome ; Leukemia, Myeloid, Acute ; Oncogenes ; Sequence Analysis, DNA