Background: A novel botulinum toxin type A (Protoxin; Protox Inc.) has been developed. Objective: To evaluate the efficacy and safety of the newly developed Protoxin compared to the approved drug onabotulinumtoxinA (OBoNT) in moderate to severe glabellar lines. Methods: Adults with a glabellar line Facial Wrinkle Scale (FWS) score of 2 (moderate) or 3 (severe) were enrolled in the study. Subjects were randomized in a 1:1 ratio to receive either Protoxin or OBoNT. A total of 20 units of botulinum toxin was injected at five sites in the glabellar region (4 units at each site). FWS scores were assessed at baseline and at weeks 4, 8, 12, and 16 post-injection. The primary endpoint was the proportion of subjects at week 4 who had a reduction of 2 or more points in FWS and a final score of 0 (none) or 1 (mild). Results: A total of 274 subjects were randomized, of whom 78.1% were female. At week 4 post-treatment, the improvement rate of glabellar lines was 62.22% in the Protoxin group and 62.96% in the OBoNT group. The lower limit of the two-sided 95% confidence interval (−12.24%) exceeded the −15% margin, confirming the non-inferiority of the new drug. Safety profiles were comparable between the two groups. Conclusion Protoxin demonstrated efficacy and safety profiles comparable to those of OBoNT in the treatment of moderate to severe glabellar lines.

Objective: To evaluate the performance of supplemental automated breast ultrasound (ABUS) added to mammography-based breast cancer screening for women with nondense breasts. Materials and Methods: A retrospective search of radiology databases at two tertiary institutions identified asymptomatic women with nondense breasts who underwent breast cancer screening using both digital mammography (DM) and supplemental ABUS between January 2020 and December 2023. We excluded women without sufficient follow-up data or those without an established final diagnosis, including histopathologic results. The performance measures of DM alone and ABUS combined with DM (ABUS plus DM) were compared. The primary outcome was the cancer detection rate (CDR), and the secondary outcomes were sensitivity and specificity. Subgroup analyses were performed for women with scattered fibroglandular density and almost entirely fatty breasts. Results: A total of 2,904 pairs of screening examinations were performed in 1,683 women (59 ± 10 years), detecting 26 cancers. In comparison with DM alone, ABUS plus DM showed higher CDR (9.0 vs. 7.9 per 1,000 examinations, P < 0.001), higher sensitivity (100% [26/26] vs. 88.5% [23/26], P < 0.001), and lower specificity (95.0% [2,735/2,878] vs. 97.9% [2,817/2,878], P < 0.001). In women with scattered fibroglandular density, ABUS increased the CDR from 7.4 to 8.5 per 1,000 examinations and improved the sensitivity from 87.0% [20/23] to 100% [23/23] (P < 0.001). In women with almost entirely fatty breasts, ABUS plus DM showed the same CDR (16.4 per 1,000 examinations) and sensitivity (100% [3/3]) as DM alone. Three cancers (11.5% [3/26]), all of which were stage T1N0, were detected only by supplemental ABUS. Conclusion Supplemental ABUS improved cancer detection and sensitivity in women with nondense breasts, with the benefits primarily observed in those with scattered fibroglandular density.

Background: Rosacea is a chronic inflammatory disorder characterized by flushing, erythema, papules/pustules, and telangiectasia. Several clinical studies have investigated the efficacy of botulinum neurotoxin A (BoNT/A) in the treatment of rosacea, but its mechanism of action remains unclear. Objective: This study aims to examine the potential role of BoNT/A in a mouse model of rosacea-like skin lesions induced by the 37-amino acid C-terminal cathelicidin peptide (LL-37). Methods: Mice were randomly divided into 4 groups: Control, LL-37, LL-37 + BoNT/A, and LL-37 + dexamethasone. Results: BoNT/A treatment alleviated skin damage, reduced skin thickness, and decreased mast cell infiltration. Furthermore, BoNT/A improved redness score severity and redness area while enhancing skin barrier function by suppressing transepidermal water loss and increasing skin hydration. At the molecular level, BoNT/A decreased the mRNA levels of interleukin (IL)-6 and tumor necrosis factor-α, which are known as pro-inflammatory cytokines. It also downregulated the expression of pyrin domain-containing protein 3, caspase-1, and IL-1 beta in the LL-37-injected dorsal skin. Furthermore, BoNT/A prevented LL-37-mediated upregulation of neurovascular-associated factors, including CD31, transient receptor potential vanilloid 1, calcitonin-related polypeptide alpha, vascular endothelial growth factor, chymase 1, and tryptase alpha/beta 1. Conclusion These results indicate that BoNT/A effectively alleviates inflammatory and vascular responses in a rosacea mouse model, highlighting its potential as a promising preventive approach for rosacea.

Background: Elevated active glucocorticoids (GCs) are implicated in skin barrier dysfunction, notably in aging and diabetes. The enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) converts inactive GCs to active forms, potentially exacerbating this dysfunction. Objective: We aimed to investigate the impact of a novel 11β-HSD1 inhibitor on skin inflammation using both in vitro and in vivo models. Methods: To elucidate the efficacy of a new 11β-HSD1 inhibitor in mitigating skin inflammation induced by various triggers, including dexamethasone treatment, ultraviolet B irradiation, and high glucose levels, in cultured human keratinocytes and the db/db mice as a type 2 diabetes murine model. In cultured keratinocytes, we assessed the effects of the 11β-HSD1 inhibitor on cortisol levels, 11β-HSD1 expression, and cytokine production under conditions simulating inflammation. In db/db mice, we evaluated the inhibitor’s impact on skin barrier function, hemoglobin A1c (HbA1c) levels, corticosterone levels, 11β-HSD1 expression, and cytokine profiles following a 2-week treatment regimen. Results: Our results demonstrated that both the novel 11β-HSD1 inhibitor and a known inhibitor reduced cortisol levels, 11β-HSD1 expression, and inflammatory cytokine production in cultured keratinocytes. In db/db mice, treatment with either inhibitor improved skin barrier function, lowered serum HbA1c levels, and decreased corticosterone, 11β-HSD1, and inflammatory cytokine expression. Conclusion A new 11β-HSD1 inhibitor, “11b-0048,” showed a significant inhibitory effect on the expression of 11β-HSD1 in keratinocytes activated by various conditions and diabetic skin.

Purpose: While MRI-based tumor regression grade (mrTRG) has shown promise in evaluating pathologic response to concurrent chemoradiotherapy (CCRT) in rectal cancer, its ability to predict pathologic complete response remains limited.This study aimed to enhance mrTRG’s diagnostic performance in predicting ypT0–1N0 status, a key factor in considering non-radical management after CCRT for locally advanced rectal cancer (LARC). Methods: This retrospective study included 430 patients with LARC who underwent radical resection following CCRT at a single referral hospital between April 2018 and September 2024. Multivariable logistic regression was used to identify predictive factors associated with achieving ypT0–1N0 status. The diagnostic performances of mrTRG1–2 alone and in combination with other factors were assessed by comparing sensitivity, specificity, positive-predictive value (PPV), negative-predictive value, and area under the curve (AUC). Results: Ninety-three patients (21.6%) achieved ypT0–1N0. In the multivariable analysis, fungating type, cT1–2, and mrTRG1–2 were independent predictors for ypT0–1N0. Integrating mrTRG with gross tumor type yielded the highest AUC of 0.689 among the combined models. For predicting ypT0–1N0, the combination of mrTRG and gross tumor type improved PPV (79.2% vs. 41.5% for mrTRG alone) while also demonstrating enhanced sensitivity compared with ycT0–1N0, the conventional MRI-based predictor (40.9% vs. 22.6%). Conclusion This study demonstrated that combining mrTRG and gross tumor type improved the PPV of mrTRG in predicting ypT0–1N0 after CCRT in LARC. Further studies are warranted to validate the role of gross tumor type in refining predictive systems for selecting candidates for non-radical treatment.

Purpose: Colorectal cancer (CRC) remains a leading cause of cancer-related mortality, necessitating the identification of novel therapeutic targets. The E3 ubiquitin ligase WW domain-containing E3 ubiquitin protein ligase 2 (WWP2) has been implicated in various cancers, yet its specific role and underlying molecular mechanisms in CRC are poorly understood. This study aimed to investigate the functional role of WWP2 in CRC progression and to elucidate its regulatory mechanisms. Methods: WWP2 expression was evaluated in CRC patient tissues and cell lines using immunohistochemistry, quantitative real-time polymerase chain reaction, and western blotting. The biological functions of WWP2 were assessed using in vitro assays for cell proliferation, migration, and invasion following adenovirus-mediated overexpression. The molecular mechanism was investigated by analyzing the protein expression levels of p53 and its downstream target, p21, via western blot. An in vivo xenograft mouse model was used to confirm the oncogenic role of WWP2. Results: WWP2 expression was significantly upregulated in CRC tissues. Overexpression of WWP2 promoted CRC cell proliferation, migration, and invasion. Mechanistically, increased WWP2 expression led to a marked reduction in the protein levels of the tumor suppressor p53. Consequently, the expression of the p53 downstream target, the cell cycle inhibitor p21, was also suppressed. In the xenograft model, WWP2 overexpression significantly enhanced tumor growth. Conclusion Our findings demonstrate that WWP2 functions as an oncogene in CRC. It promotes cancer progression by destabilizing the tumor suppressor p53 and downregulating p21. This study highlights the WWP2-p53-p21 axis as a potential novel therapeutic target for CRC.

Background/Aims: Biliary tract cancer (BTC) is a rare malignancy with poor prognosis. We investigated genomic determinants of clinical benefit from gemcitabine, cisplatin, and nab-paclitaxel (GAP) versus gemcitabine and cisplatin (GC) in advanced BTC. Methods: Clinical and genomic data using TruSight Oncology 500 were analyzed from patients treated with GAP (N=198) or GC (N=89) as first-line therapy. Results: With a median follow-up of 33.0 months, GAP modestly improved progression-free survival (PFS) (hazard ratio [HR] 0.764; 95% confidence interval [CI] 0.591–0.989) without significant overall survival (OS) difference compared to GC. Genomic profiling revealed frequent alterations in TP53 (35.2%), KRAS (16.4%), SMAD4 (10.5%), and TNFRSF14 (10.5%), involving RTK/RAS (44.3%), TP53 (41.8%), and PI3K (20.2%) pathways. Single-gene mutations did not predict treatment benefit. However, pathway-level analysis identified PI3K pathway activation as significantly associated with inferior PFS (HR 2.148; 95% CI 1.478–3.124) and OS (HR 2.096; 95% CI 1.413–3.109) in patients receiving GAP, an effect not observed with GC. Importantly, GAP conferred clinical benefit only in patients without PI3K pathway activation, while no survival advantage was seen in those with such alterations (Pinteraction=0.023 for PFS, Pinteraction=0.003 for OS). Similar results were obtained in the independent validation cohort treated with GAP (N=103) or GC (N=64) for BTC. Conclusions Genomic profiling using next-generation sequencing identified PI3K pathway activation as key molecular determinant that differentiates patient outcomes between GAP and GC treatments in advanced BTC.

Purpose: This study aimed to compare the acute effects of isometric handgrip (IHG) and wall squat (IWS) exercise on 24-hour ambulatory blood pressure (BP) and related indices in young men with prehypertension. Methods: Ten young men with prehypertension (aged 25.0±2.3 years) completed three randomized crossover conditions: IHG, IWS, and control. Twenty-four-hour ambulatory BP monitoring was used to assess 24-hour, daytime, and nighttime mean BP, BP variability (BPV; average real variability and standard deviation), morning BP, and nocturnal dipping pattern. Office BP was measured at baseline, 30 minutes, and 90 minutes after each condition. Results: Twenty-four hour, daytime, and nighttime systolic and diastolic BP did not differ significantly among conditions. BPV indices also showed no significant between-condition differences across 24-hour, daytime, or nighttime periods. Nocturnal systolic BP dipping averaged 5%–8% and did not differ among conditions, indicating a nondipper pattern in all trials. Morning systolic BP, sleep-trough surge, and prewaking surge were similar across conditions. Office BP showed no significant condition or interaction effects; however, both IHG and IWS tended to lower BP at 90 minutes compared with control session. Conclusion A single bout of IHG or IWS did not elicit significant changes in 24-hour ambulatory BP, BPV, morning BP, or dipping pattern in young men with prehypertension. Nonetheless, the small acute reductions in office and morning BP suggest that isometric exercise may have potential as a time-efficient adjunctive strategy for early BP management. Larger and longer-term studies are needed to confirm these findings.

Purpose: Radiotherapy is used to reduce the risk of breast cancer recurrence after surgery, but it is a potential cause of secondary cancer. We validated the risk of secondary cancer in primary breast cancer who received radiotherapy compared with those who did not from a matched cohort using a large-scale observational study of the Observational Health Data Sciences and Informatics (OHDSI) data network. Materials and Methods: A retrospective comparative cohort study using propensity score-matched cohorts was performed using two Observational Medical Outcome Partnership common data model databases, from tertiary general hospitals in South Korea. Among female patients who underwent surgery after the diagnosis of breast cancer, the risk of secondary primary malignant occurrence after 1:1 matching was analyzed. Results: Among 27,078 patients with breast cancer, there was no significant difference in the risk of secondary cancer following radiotherapy in 4,426 patients after 1:1 propensity-score matching. Further, there were no significant differences in the sensitivity analysis according to age, latency period, and number of radiation treatments. Conclusion There was no difference in the risk of secondary cancer in the patients diagnosed with breast cancer depending on whether or not radiotherapy was performed after surgery. In the future, it is necessary to analyze including data generated during cancer treatment.

Purpose: Chronic myeloid leukemia (CML) in children, adolescents, and young adults is rare and differs from older adults. This study evaluated the outcomes of allogeneic hematopoietic stem cell transplantation (HSCT) in young Korean CML patients during the tyrosine kinase inhibitor (TKI) era. Materials and Methods: A retrospective analysis of 35 CML patients aged < 40 years who underwent allogeneic HSCT from 2009 to 2019 was conducted using Korean Blood and Marrow Transplantation Registry data. Patients were grouped by age < 20 years at HSCT (group 1, n=15) and 20-40 years at HSCT (group 2, n=20). Survival outcomes including overall survival (OS), relapse-free survival (RFS), and event-free survival (EFS) were analyzed using the Kaplan-Meier method. Results: The median time between diagnosis and HSCT was 8.9 months. All the patients achieved engraftment but platelet recovery was significantly slower in group 1 (p=0.034). Acute and chronic graft-versus-host disease occurred in 54.3% and 34.3%, respectively. Five-year OS, RFS, and EFS rates of total patients were 66.8%, 50.8%, and 47.6%, with better OS was observed in group 1 by multivariable analysis (p=0.048). Disease status at HSCT was a significant predictor of OS (p=0.028), RFS (p=0.003), and EFS (p=0.004). Disease progression occurred in 13 out of 35 patients (37.1%); treatment-related mortality accounted for 63.6% of deaths (7 out of 11). Conclusion When performed at a younger age, allogeneic HSCT result in superior outcome in CML. Achieving remission before HSCT is critical for improved outcomes, highlighting the importance of pretransplant remission via optimal TKI strategies and minimal residual disease monitoring.