We identified drugs or mechanisms targeting ABCB1 (or P-glycoprotein; P-gp)-overexpressing drug-resistant cancer populations, given that these cells play a key role in tumor recurrence. Specifically, we searched for Akt inhibitors that could increase cytotoxicity in P-gp-overexpressing drug-resistant cancer cells. We performed cytotoxicity assays using five cell lines: 1. MCF-7/ADR, 2. KBV20C cancer cells (P-gp overexpression, vincristine [VIC] resistance, and GSK690693-resistance), 3. MCF-7, 4. normal HaCaT cells (non-P-gp-overexpressing, VIC-sensitive, and GSK690693-sensitive), and 5. MDA-MB-231 cancer cells (non-Pgp overexpression, relatively VIC-resistance, and GSK690693-sensitive). Herein, we found that low-dose perifosine markedly and selectively sensitizes both MCF-7/ADR and KBV20C drug-resistant cancer cells exhibiting P-gp overexpression. Compared with other Akt inhibitors (AZD5363, BKM120, and GSK690693), low-dose perifosine specifically sensitized P-gp-overexpressing resistant MCF-7/ADR cancer cells. Conversely, Akt inhibitors (other than perifosine) could enhance sensitization effects in drugsensitive MCF-7 and HaCaT cells. Considering that perifosine has both an alkyl-phospholipid structure and is an allosteric inhibitor for membrane-localizing Akt-targeting, we examined structurally and functionally similar Akt inhibitors (miltefosine and MK-2206).However, we found that these inhibitors were non-specific, suggesting that the specificity of perifosine in P-gp-overexpressing resistant cancer cells is unrelated to phospholipid localizing membranes or allosteric inhibition. Furthermore, we examined the molecular mechanism of low-dose perifosine in drug-resistant MCF-7/ADR cancer cells. MCF-7/ADR cells exhibited increased apoptosis via G2 arrest and autophagy induction. However, no increase in P-gp-inhibitory activity was observed in drug-resistant MCF-7/ADR cancer cells. Single low-dose perifosine treatment exerted a sensitization effect similar to co-treatment with VIC in P-gp-overexpressing drug-resistant MCF-7/ADR cancer cells, suggesting that single treatment with low-dose perifosine is a more powerful tool against P-gp-overexpressing drug-resistant cancer cells. These findings could contribute to its clinical use as a first-line treatment, explicitly targeting P-gp-overexpressing resistant cancer populations in heterogeneous tumor populations.Therefore, perifosine may be valuable in delaying or reducing cancer recurrence by targeting P-gp-overexpressing drug-resistant cancer cells.

Purpose: To investigate the clinical characteristics of South Korean patients with pericentral retinitis pigmentosa (RP) and to identify clinical biomarkers associated with rapid visual acuity decline based on baseline factors. Methods: This retrospective study included 59 eyes of 31 patients diagnosed with pericentral RP. Comprehensive ophthalmological examinations and genetic sequencing were conducted to assess the baseline characteristics. For biomarker analysis, eyes were categorized into two groups based on the annual rate of change in visual acuity. The clinical findings of the two groups were evaluated to identify the biomarkers associated with rapid loss of visual acuity. Results: Patients with pericentral RP in this study exhibited a mean best-corrected visual acuity of 0.17 ± 0.23 in logarithm of the minimum angle of resolution. The visual field test showed annular or semicircular scotoma with relatively preserved periphery and 27 eyes (45.8%) exhibited no macular complications in optical coherence tomography. Genetic analysis identified genes associated with previous typical and pericentral RP studies but also highlighted that many genetic causes of pericentral RP remain unidentified. Of the 55 eyes for which the rate of visual acuity change could be estimated, 18 exhibited an annual decline of ≥10%, whereas 37 showed an annual decline of <10%. Male sex and prolonged b-wave latency on dark-adapted 0.01 electroretinogram correlated with rapid visual acuity decline in the multivariate analysis. Conclusions South Korean patients with pericentral RP exhibited a milder phenotype compared to typical RP patients reported in previous studies. Genetic analysis revealed heterogeneity, with mutations in some genes commonly associated with milder forms of RP. Male sex and prolonged b-wave latency on dark-adapted 0.01 electroretinogram were significant biomarkers for predicting rapid visual acuity decline. Monitoring initial b-wave latency is important for predicting visual decline, particularly in male patients with pericentral RP.

Objective: To compare a deep learning (DL)-accelerated non-enhanced abbreviated MRI (AMRI DL) protocol with standard AMRI (AMRI STD) of the liver in terms of image quality and malignant focal lesion detection. Materials and Methods: This retrospective study included 155 consecutive patients (110 male; mean age 62.4 ± 11 years) from two sites who underwent standard liver MRI and additional AMRIDL sequences, specifically DL-accelerated single-shot fast-spin echo (SSFSE DL) and DL-accelerated diffusion-weighted imaging (DWIDL). Additional MRI phantom experiments assessed signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and apparent diffusion coefficient (ADC) values. Three reviewers evaluated AMRIDL and AMRI STD protocols for image quality using a five-point Likert scale and identified malignant hepatic lesions. Image quality scores and per-lesion sensitivities were compared between AMRIDL and AMRI STD using the Wilcoxon signed-rank test and logistic regression with generalized estimating equations, respectively. Results: Phantom experiments demonstrated comparable SNR and higher CNR for SSFSE DL compared to SSFSE STD, with similar ADC values for DWIDL and DWI STD. Among the 155 patients, 130 (83.9%) had chronic liver disease or a history of intra- or extrahepatic malignancy. Of 104 malignant focal lesions in 64 patients, 58 (55.8%) were hepatocellular carcinomas (HCCs), 38 (36.5%) were metastases, four (3.8%) were cholangiocarcinomas, and four (3.8%) were lymphomas. The pooled per-lesion sensitivity across three readers was 97.6% for AMRIDL, comparable to 97.6% for AMRI STD. Compared with AMRI STD, AMRIDL demonstrated superior image quality regarding structural sharpness, artifacts, and noise (all P < 0.001) and reduced the average scan time by approximately 50% (2 min 29 sec vs. 4 min 11 sec). In patients with chronic liver disease, AMRIDL achieved a 96.6% per-lesion sensitivity for HCC detection, similar to 96.5% for AMRI STD (P > 0.05). Conclusion The AMRIDL protocol offers comparable sensitivity for detecting malignant focal lesions, including HCC while significantly enhancing image quality and reducing scan time by approximately 50% compared to AMRI STD.

Background: Small cell lung cancer (SCLC) is called ‘smoker’s disease’ because it is strongly associated with smoking and most cases occur in smokers. However, it can also occur in never smokers. We investigated the clinical features of never smokers with SCLC and compared their treatment outcomes with those of smokers with SCLC. Methods: We retrospectively reviewed the clinical data of patients who had proven SCLC and had received chemotherapy at a single cancer center between July 2002 and April 2021. Results: Of 1,643 patients, 1,416 (86.2%) were enrolled in this study. A total of 162 (11.4%) and 1,254 (88.6%) patients were never smokers and smokers, respectively. There were more female never smokers than smokers (n=130; 80.2% vs. 79, 6.3%, p=0.000), and the incidence of ischemic heart disease was lower among never smokers than among smokers (4/1,416, [2.5%] vs. 83/1,416 [6.6%], p=0.036). Never smokers showed less symptoms at diagnosis than smokers (80.9% vs. 87.2%, p=0.037); however, they showed more toxicity after first-line treatment (61.7% vs. 47.8%, p=0.001). The objective response rate (ORR) was significantly higher in never smokers (74.1% vs. 59.6%, p=0.000). In the multivariate analysis, never smoking and second-line treatment were associated with a better ORR. However, progression-free survival and overall survival were not significantly different between never smokers and smokers. Conclusion In conclusion, never smokers accounted for 11.4% of patients with SCLC. They had distinguishing clinical characteristics and showed better chemotherapeutic responses than smokers.

Purpose: Adjuvant treatment for craniopharyngioma after surgery is controversial. Adjuvant external beam radiation therapy (EBRT) can increase the risk of long-term sequelae. Stereotactic radiosurgery (SRS) is used to reduce treatment-related toxicity.In this study, we compared the treatment outcomes and toxicities of adjuvant therapies for craniopharyngioma. Materials and Methods: We analyzed patients who underwent craniopharyngioma tumor removal between 2000 and 2017. Of the 153 patients, 27 and 20 received adjuvant fractionated EBRT and SRS, respectively. We compared the local control (LC), progression-free survival (PFS), and overall survival between groups that received adjuvant fractionated EBRT, SRS, and surveillance. Results: The median follow-up period was 77.7 months. For SRS and surveillance, the 10-year LC was 57.2% and 57.4%, respectively. No local progression was observed after adjuvant fractionated EBRT. One patient in the adjuvant fractionated EBRT group died owing to glioma 94 months after receiving radiotherapy (10-year PFS: 80%). The 10-year PFS was 43.6% and 50.7% in the SRS and surveillance groups, respectively. The treatment outcomes significantly differed according to adjuvant treatment in nongross total resection (GTR) patients. Additional treatment-related toxicity was comparable in the adjuvant fractionated EBRT and other groups. Conclusion Adjuvant fractionated EBRT could be effective in controlling local failure, especially in patients with non-GTR, while maintaining acceptable treatment-related toxicity.

Purpose: To investigate the clinical characteristics of South Korean patients with pericentral retinitis pigmentosa (RP) and to identify clinical biomarkers associated with rapid visual acuity decline based on baseline factors. Methods: This retrospective study included 59 eyes of 31 patients diagnosed with pericentral RP. Comprehensive ophthalmological examinations and genetic sequencing were conducted to assess the baseline characteristics. For biomarker analysis, eyes were categorized into two groups based on the annual rate of change in visual acuity. The clinical findings of the two groups were evaluated to identify the biomarkers associated with rapid loss of visual acuity. Results: Patients with pericentral RP in this study exhibited a mean best-corrected visual acuity of 0.17 ± 0.23 in logarithm of the minimum angle of resolution. The visual field test showed annular or semicircular scotoma with relatively preserved periphery and 27 eyes (45.8%) exhibited no macular complications in optical coherence tomography. Genetic analysis identified genes associated with previous typical and pericentral RP studies but also highlighted that many genetic causes of pericentral RP remain unidentified. Of the 55 eyes for which the rate of visual acuity change could be estimated, 18 exhibited an annual decline of ≥10%, whereas 37 showed an annual decline of <10%. Male sex and prolonged b-wave latency on dark-adapted 0.01 electroretinogram correlated with rapid visual acuity decline in the multivariate analysis. Conclusions South Korean patients with pericentral RP exhibited a milder phenotype compared to typical RP patients reported in previous studies. Genetic analysis revealed heterogeneity, with mutations in some genes commonly associated with milder forms of RP. Male sex and prolonged b-wave latency on dark-adapted 0.01 electroretinogram were significant biomarkers for predicting rapid visual acuity decline. Monitoring initial b-wave latency is important for predicting visual decline, particularly in male patients with pericentral RP.

Objective: To compare a deep learning (DL)-accelerated non-enhanced abbreviated MRI (AMRI DL) protocol with standard AMRI (AMRI STD) of the liver in terms of image quality and malignant focal lesion detection. Materials and Methods: This retrospective study included 155 consecutive patients (110 male; mean age 62.4 ± 11 years) from two sites who underwent standard liver MRI and additional AMRIDL sequences, specifically DL-accelerated single-shot fast-spin echo (SSFSE DL) and DL-accelerated diffusion-weighted imaging (DWIDL). Additional MRI phantom experiments assessed signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and apparent diffusion coefficient (ADC) values. Three reviewers evaluated AMRIDL and AMRI STD protocols for image quality using a five-point Likert scale and identified malignant hepatic lesions. Image quality scores and per-lesion sensitivities were compared between AMRIDL and AMRI STD using the Wilcoxon signed-rank test and logistic regression with generalized estimating equations, respectively. Results: Phantom experiments demonstrated comparable SNR and higher CNR for SSFSE DL compared to SSFSE STD, with similar ADC values for DWIDL and DWI STD. Among the 155 patients, 130 (83.9%) had chronic liver disease or a history of intra- or extrahepatic malignancy. Of 104 malignant focal lesions in 64 patients, 58 (55.8%) were hepatocellular carcinomas (HCCs), 38 (36.5%) were metastases, four (3.8%) were cholangiocarcinomas, and four (3.8%) were lymphomas. The pooled per-lesion sensitivity across three readers was 97.6% for AMRIDL, comparable to 97.6% for AMRI STD. Compared with AMRI STD, AMRIDL demonstrated superior image quality regarding structural sharpness, artifacts, and noise (all P < 0.001) and reduced the average scan time by approximately 50% (2 min 29 sec vs. 4 min 11 sec). In patients with chronic liver disease, AMRIDL achieved a 96.6% per-lesion sensitivity for HCC detection, similar to 96.5% for AMRI STD (P > 0.05). Conclusion The AMRIDL protocol offers comparable sensitivity for detecting malignant focal lesions, including HCC while significantly enhancing image quality and reducing scan time by approximately 50% compared to AMRI STD.

Purpose: This study aimed to characterize the clinical patterns and severity of brain injury in neonates who survived extracorporeal membrane oxygenation (ECMO) therapy for acute respiratory failure during the neonatal period, to evaluate their short-term neurodevelopmental outcomes, and to identify the factors associated with these outcomes. Methods: We retrospectively reviewed the medical records of neonates who survived ECMO between 2018 and 2024. Based on brain magnetic resonance imaging (MRI) findings, the patients were classified into two groups: no/mild and moderate/severe brain injury. Neurodevelopmental outcomes were assessed at 12–40 months of age using the Bayley Scale of Infant Development II/III and/or the Korean Developmental Screening Test. Results: Among the 19 neonates included in the study, 18 (94.7%) showed varying degrees of brain injury on MRI (mild: 12, moderate: 1, severe: 5). Neonates with moderate/severe brain injury had significantly longer durations of ECMO support and extended durations of mechanical ventilation and were more likely to receive continuous renal replacement therapy than those with no or mild injury. Developmental delay was identified in 36.8% of survivors and was significantly associated with prolonged mechanical ventilation, longer neonatal intensive care unit stays, and a higher incidence of seizures. Conclusion Brain injury is frequently observed on MRI in neonates treated with ECMO. However, its direct association with adverse neurodevelopmental outcomes is not definitive. Since MRI findings alone cannot predict developmental outcomes, clinical and environmental factors should be integrated into prognostic assessments.