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14 pages, 1626 KB  
Article
Deep Learning-Based Prediction of Individual Cell α-Dispersion Capacitance from Morphological Features
by Tae Young Kang, Soojung Kim, Yoon-Hwae Hwang and Kyujung Kim
Biosensors 2025, 15(11), 753; https://doi.org/10.3390/bios15110753 - 10 Nov 2025
Viewed by 131
Abstract
The biophysical characteristics of cellular membranes, particularly their electrical properties in the α-dispersion frequency domain, offer valuable insights into cellular states and are increasingly important for cancer diagnostics through epidermal growth factor receptor (EGFR) expression analysis. However, a critical limitation in these [...] Read more.
The biophysical characteristics of cellular membranes, particularly their electrical properties in the α-dispersion frequency domain, offer valuable insights into cellular states and are increasingly important for cancer diagnostics through epidermal growth factor receptor (EGFR) expression analysis. However, a critical limitation in these electrical measurements is the confounding effect of morphological changes that inevitably occur during prolonged observation periods. These shape alterations significantly impact measured capacitance values, potentially masking true biological responses to epidermal growth factor (EGF) stimulation that are essential for cancer detection. In this study, we attempted to address this fundamental challenge by developing a deep learning method that establishes a direct computational relationship between cellular morphology and electrical properties. We combined optical trapping technology and capacitance measurements to generate a comprehensive dataset of HeLa cells under two different experimental conditions: (i) DPBS treatment and (ii) EGF stimulation. Our convolutional neural network (CNN) architecture accurately predicts 401-point capacitance spectra (0.1–2 kHz) from binary morphological images at low frequencies (0.1–0.8 kHz, < 10% error rate). This capability allows for the identification and subtraction of morphology-dependent components from measured capacitance changes, effectively isolating true biological responses from morphological artefacts. The model demonstrates remarkable prediction performance across diverse cell morphologies in both experimental conditions, validating the robust relationship between cellular shape and electrical characteristics. Our method significantly improves the precision and reliability of EGFR-based cancer diagnostics by providing a computational framework for a morphology-induced measurement error correction. Full article
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13 pages, 1991 KB  
Article
Revisiting p53 Immunohistochemical Staining and Its Prognostic Implications in Advanced EGFR-Mutated Lung Adenocarcinoma
by Feng-Che Kuan, Shun-Fu Chang, Yao-Ren Yang, Yu-Ying Wu, Fen-Fen Chen, Kam-Fai Lee, Chen-Lin Chi, Meng-Hung Lin and Chung-Sheng Shi
Cancers 2025, 17(21), 3577; https://doi.org/10.3390/cancers17213577 - 5 Nov 2025
Viewed by 260
Abstract
Background/Objectives: TP53 mutations in advanced epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer could worsen prognosis. Therefore, we aimed to investigate the clinical significance of TP53 mutations and p53 expression in these patients. Methods: Patients with advanced/metastatic EGFR-mutated lung adenocarcinoma treated with [...] Read more.
Background/Objectives: TP53 mutations in advanced epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer could worsen prognosis. Therefore, we aimed to investigate the clinical significance of TP53 mutations and p53 expression in these patients. Methods: Patients with advanced/metastatic EGFR-mutated lung adenocarcinoma treated with first-line tyrosine kinase inhibitors were retrospectively enrolled. Sanger sequencing was performed to detect TP53 mutations and immunohistochemical staining was used to verify p53 protein expression levels. Kaplan-Meier and Cox proportional hazards analyses were used to estimate survival and hazard ratio (HR) with 95% confidence interval (CI). Results: The study involved 83 patients with adequate tumor samples for TP53/p53 analysis. Patients with tumor p53 immunostaining ≥50% showed significantly better overall survival (OS) (HR: 0.49 [95% CI: 0.30–0.81], p < 0.001), but TP53 mutations were not associated with inferior progression-free survival (PFS) or OS (missense vs. wild-type [PFS, HR: 0.68 (95% CI: 0.40–1.15), p = 0.151; OS, HR: 0.88 (95% CI: 0.56–1.42), p = 0.599]). Areas under the receiver operating characteristic curves of TP53 mutations with different cut-off values for p53 positivity were 0.51–0.56. The Kaplan-Meier survival analysis revealed significant survival benefits in patients with EGFR L858R substitution and tumor p53 immunostaining ≥50% (median PFS: 8.0 vs. 5.3; median OS: 20.4 vs. 15.3 months; log-rank p = 0.025 and 0.049, respectively). Conclusions: Tumor p53 immunostaining (≥50%) was associated with better OS, especially in patients with TP53 mutations or L858R. Prospective clinical trials are required to explore the prognostic significance of p53 expression in the genomic era of TP53 mutations. Full article
(This article belongs to the Section Cancer Biomarkers)
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16 pages, 1040 KB  
Article
Treatment Patterns by Physiologic Age in Older Adults with Early-Stage Breast Cancer: A Single Institution Retrospective Study
by Eliza H. Lorentzen, Yu-Jen Chen, Maria Harvey and Christina A. Minami
J. Clin. Med. 2025, 14(21), 7853; https://doi.org/10.3390/jcm14217853 - 5 Nov 2025
Viewed by 152
Abstract
Background/Objectives: Older adults with breast cancer may suffer from over- and undertreatment if intensity of therapy does not align with their physiologic age. We sought to evaluate the association between physiologic age, chronologic age, and treatment patterns in women ≥ 70 years [...] Read more.
Background/Objectives: Older adults with breast cancer may suffer from over- and undertreatment if intensity of therapy does not align with their physiologic age. We sought to evaluate the association between physiologic age, chronologic age, and treatment patterns in women ≥ 70 years with non-metastatic breast cancer. Methods: Patients ≥ 70 diagnosed with non-metastatic breast cancer 10/2021–3/2024 who had received surgical therapy and frailty (Geriatric-8) and life expectancy (Schonberg index) screening at our institution were identified from our institutional database. Descriptive analyses were run using chi-square tests of proportion. In the largest subgroup (patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2)-disease), multivariate logistic regression adjusting for patient- and disease-level characteristics was used to assess the relationship between life expectancy < 10 years and the omission of sentinel lymph node biopsy (SLNB) and radiation therapy (RT). Results: Of 272 patients, 104 (38.2%) screened positive for frailty and 64 (23.5%) had a life expectancy of <10 years. On bivariate analysis, a higher proportion of frail patients (44 (42.3%) had a life expectancy < 10 years, while 20 (11.9%) robust patients had a life expectancy < 10 years (p < 0.001). Most patients (226, 83.1%) had HR+/HER-2 negative disease; 10 (3.7%) had HER2+ disease; and 33 (12.1%) had triple-negative breast cancer (TNBC) (p < 0.001). Life expectancy was not significantly associated with omission of SLNB (life expectancy < 10 years: reference; life expectancy ≥ 10 years: OR 0.81 95% CI [0.20–3.28]) or RT (life expectancy < 10 years: reference; life expectancy ≥ 10 years: OR 1.14, 95% CI 0.44–2.93]) in patients with stage I–II HR+/HER-2− disease on adjusted analysis. Conclusions: While patients at risk for frailty and limited life expectancy are relatively common in our population, these measures may not significantly influence patient and clinician treatment decision making. Future efforts to tailor therapy by measures of physiologic age are needed. Full article
(This article belongs to the Special Issue Breast Cancer: Symptoms, Types, Causes & Treatment)
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24 pages, 4341 KB  
Article
EGFR mRNA-Engineered Mesenchymal Stem Cells (MSCs) Demonstrate Radioresistance to Moderate Dose of Simulated Cosmic Radiation
by Fay Ghani, Peng Huang, Cuiping Zhang and Abba C. Zubair
Cells 2025, 14(21), 1719; https://doi.org/10.3390/cells14211719 - 1 Nov 2025
Viewed by 340
Abstract
Galactic cosmic ray (GCR) radiation is a major barrier to human space exploration beyond Earth’s magnetic field protection. Mesenchymal stem cells (MSCs) are found in all organs and play a critical role in repair and regeneration of tissue. We engineered bone marrow-derived MSCs [...] Read more.
Galactic cosmic ray (GCR) radiation is a major barrier to human space exploration beyond Earth’s magnetic field protection. Mesenchymal stem cells (MSCs) are found in all organs and play a critical role in repair and regeneration of tissue. We engineered bone marrow-derived MSCs and evaluated their response to ionizing radiation exposure. Epidermal growth factor receptor (EGFR) expression by certain types of cancers has been shown to induce radioresistance. In this study, we tested the feasibility of transfecting MSCs to overexpress EGFR (eMSC-EGFR) and their capacity to tolerate and recover from X-ray exposure. Quantitative real-time PCR (qRT-PCR) and immunoblotting results confirmed the efficient transfection of EGFR into MSCs and EGFR protein production. eMSC-EGFR maintained characteristics of human MSCs as outlined by the International Society for Cell & Gene Therapy. Then, engineered MSCs were exposed to various dose rates of X-ray (1–20 Gy) to assess the potential radioprotective role of EGFR overexpression in MSCs. Post-irradiation analysis included evaluation of morphology, cell proliferation, viability, tumorigenic potential, and DNA damage. eMSC-EGFR showed signs of radioresistance compared to naïve MSCs when assessing relative proliferation one week following exposure to 1–8 Gy X-rays, and significantly lower DNA damage content 24 h after exposure to 4 Gy. We establish for the first time the efficient generation of EGFR overexpressing MSCs as a model for enhancing the human body to tolerate and recover from moderate dose radiation injury in long-term manned space travel. Full article
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15 pages, 1843 KB  
Article
Real-World Evidence of Long-Term Disease Control in HER2-Positive Metastatic Breast Cancer Patients Treated with a First-Line Combination of Trastuzumab and/or Pertuzumab Plus Chemotherapy
by Loïc Chaigneau, Eva Lapp, Taha Jai, Erion Dobi, Berenger Martin, Elsa Curtit and Virginie Nerich
Cancers 2025, 17(21), 3532; https://doi.org/10.3390/cancers17213532 - 31 Oct 2025
Viewed by 231
Abstract
Background and Method: The overexpression of the human epidermal growth factor receptor 2 (HER2) in breast cancer is correlated with accelerated tumor progression and an unfavorable clinical outcome. Since the introduction of trastuzumab in 2002, the treatment of HER2-positive breast cancer has [...] Read more.
Background and Method: The overexpression of the human epidermal growth factor receptor 2 (HER2) in breast cancer is correlated with accelerated tumor progression and an unfavorable clinical outcome. Since the introduction of trastuzumab in 2002, the treatment of HER2-positive breast cancer has been revolutionized, leading to significant improvements in survival. This retrospective, multicenter study aimed to describe the characteristics of patients with HER2-positive metastatic breast cancer (MBC) who maintained disease control for a minimum of three years after first-line therapy with trastuzumab and/or pertuzumab combined with chemotherapy. Results: Among 280 eligible patients, 48 (17.5%) were classified as long-term responders. The study population primarily consisted of women with a median age of 56.7 years at diagnosis; de novo metastatic presentation was observed in approximately 70% of cases. An objective response rate of nearly 90% was observed, with a median duration of response of 5.8 years. Median progression-free survival was 11.0 years [95% CI: 6.6—not reached], and median overall survival was not reached [95% CI: 10.9—not reached]. Furthermore, about 15% of patients were able to discontinue systemic therapy without immediate disease progression. Discussion and Conclusions: These findings indicate the potential of achieving prolonged disease control in a subset of patients with HER2-positive MBC, raising questions about therapeutic intensification and potential treatment discontinuation strategies. This study underscores the need for future research to identify predictive factors of durable response and assess the feasibility of adaptive treatment strategies, including planned treatment discontinuation. Full article
(This article belongs to the Section Cancer Metastasis)
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15 pages, 860 KB  
Article
Association Between Serum Growth Factors and Risk of Acute Exacerbation in Chronic Obstructive Pulmonary Disease: A One-Year Prospective Study
by Hong-Yih Tien, Chung-Yu Chen, Chong-Jen Yu and Hao-Chien Wang
Int. J. Mol. Sci. 2025, 26(21), 10584; https://doi.org/10.3390/ijms262110584 - 30 Oct 2025
Viewed by 318
Abstract
Chronic obstructive pulmonary disease (COPD) is characterized by persistent airflow limitation associated with enhanced chronic airway inflammation. Growth factors implicated in COPD’s inflammatory processes may serve as biomarkers for disease progression and exacerbation risk. This study evaluated the relationship between serum growth factors [...] Read more.
Chronic obstructive pulmonary disease (COPD) is characterized by persistent airflow limitation associated with enhanced chronic airway inflammation. Growth factors implicated in COPD’s inflammatory processes may serve as biomarkers for disease progression and exacerbation risk. This study evaluated the relationship between serum growth factors and COPD exacerbations over one year. Serum levels of eleven growth factors, including brain-derived neurotrophic factor (BDNF), leukemia inhibitory factor (LIF), fibroblast growth factor-2 (FGF-2), vascular endothelial growth factor (VEGF), nerve growth factor (NGF), epidermal growth factor (EGF), and stem cell factor (SCF), were measured in COPD patients at baseline. Participants were followed prospectively for one year, and associations between these biomarkers and acute exacerbations (AE) and frequent acute exacerbations (Frequent AE) were assessed using statistical analyses and receiver operating characteristic (ROC) curves. Among the study population, 42 patients experienced at least one AE within the follow-up period. Lower serum FGF-2 levels were significantly associated with increased AE risk (adjusted odds ratio significant after covariate adjustment). ROC analysis identified FGF-2 ≤ 9.12 pg/mL as a predictor of AE (AUC = 0.614, sensitivity = 64.3%, specificity = 57.1%, p = 0.032). For Frequent AE, eight patients experienced multiple exacerbations and exhibited significantly lower levels of NGF, EGF, FGF-2, and LIF. After adjustment, NGF remained significantly predictive; NGF ≤ 25.23 pg/mL demonstrated strong discriminatory power for Frequent AE (AUC = 0.797, p < 0.001). However, interpretations are limited by the small Frequent AE subgroup. Serum growth factors, particularly FGF-2 and NGF, are associated with COPD exacerbation risk. Lower serum FGF-2 may indicate a higher likelihood of acute exacerbations, while lower NGF strongly predicts frequent exacerbations. Larger studies and longer follow-ups are needed to confirm these biomarkers’ predictive utility. Full article
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15 pages, 3140 KB  
Systematic Review
Systematic Review of Line-Field Confocal Optical Coherence Tomography for Diagnosing Pre-Malignant and Malignant Keratinocytic Lesions: Optimising the Workflow
by Maria Luísa Santos e Silva Caldeira Marques, Justin Hero, Mary-Ann el-Sharouni, Marta García Bustínduy and Pascale Guitera
Diagnostics 2025, 15(21), 2746; https://doi.org/10.3390/diagnostics15212746 - 29 Oct 2025
Viewed by 469
Abstract
Background: Line-field confocal optical coherence tomography (LC-OCT) is a non-invasive imaging technique providing high-resolution en-face and cross-sectional views of the epidermis and superficial dermis for in vivo characterisation of actinic keratosis (AK), Bowen’s disease (BD) and squamous cell carcinoma (SCC). Despite its [...] Read more.
Background: Line-field confocal optical coherence tomography (LC-OCT) is a non-invasive imaging technique providing high-resolution en-face and cross-sectional views of the epidermis and superficial dermis for in vivo characterisation of actinic keratosis (AK), Bowen’s disease (BD) and squamous cell carcinoma (SCC). Despite its promise, standardised imaging protocols are lacking. Objective: This systematic review aims to assess the utility of LC-OCT for diagnosing AK, BD and SCC, with particular emphasis on workflow optimisation and protocol standardisation. Methods: A systematic literature search was performed using PubMed, Embase, and Scopus databases (January 2018–October 2024). Two reviewers independently screened the records, extracted data and applied the Confidence in the Evidence from Reviews of Qualitative research (CERQual) framework to assess confidence in key findings. Results: Eleven studies met the inclusion criteria. LC-OCT reliably identified key histopathological correlates. Across studies, LC-OCT consistently visualised hyperkeratosis, keratinocytic atypia, parakeratosis, and acanthosis, as well as characteristic vascular alterations and dermal remodeling. LC-OCT also demonstrated its capacity to detect invasive features by revealing disruptions in the dermo-epidermal junction and the presence of tumour strands infiltrating the dermis. Multimodal imaging combined with technical optimisations such as minimal probe pressure, paraffin oil coupling, and dermoscopy-guided localisation, substantially improved image resolution and interobserver concordance. Conclusions: This systematic review provides a basis for establishing standardised LC-OCT imaging protocols in keratinocytic tumours. While LC-OCT shows promise as a non-invasive diagnostic tool, further multicenter studies are needed to refine imaging workflows and evaluate the integration of artificial intelligence-based analysis to improve diagnostic accuracy and reproducibility. Full article
(This article belongs to the Section Biomedical Optics)
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19 pages, 9803 KB  
Article
Shikonin-Loaded Nanoparticles Attenuate Particulate Matter-Induced Skin Injury by Inhibiting Oxidative Stress and Inflammation
by Feifei Huang, Qinghua Tang, Ke Wang, Lingmei Zhou, Ruiwei Liao, Zhuoya Wang, Yan Li, Lin Zhou and Ming Li
Antioxidants 2025, 14(11), 1301; https://doi.org/10.3390/antiox14111301 - 29 Oct 2025
Viewed by 500
Abstract
Exposure to fine particulate matter (PM2.5) poses a major threat to skin health, yet effective prevention strategies remain limited. Shikonin, a naphthoquinone derived from Lithospermum erythrorhizon, exhibits potent antioxidant and anti-inflammatory activities. However, its therapeutic application is limited by low bioavailability. To address [...] Read more.
Exposure to fine particulate matter (PM2.5) poses a major threat to skin health, yet effective prevention strategies remain limited. Shikonin, a naphthoquinone derived from Lithospermum erythrorhizon, exhibits potent antioxidant and anti-inflammatory activities. However, its therapeutic application is limited by low bioavailability. To address this limitation, we developed shikonin-loaded nanoparticles (SH-NPs) using an emulsion solvent evaporation method and characterized their physicochemical properties. The protective effects of SH-NPs against PM2.5-induced skin damage were evaluated in a mouse model. The SH-NPs exhibited favorable characteristics, including a mean particle size of 209.03 ± 2.45 nm, a PDI of 0.064 ± 0.03, and a zeta potential of –17.69 ± 2.06 mV. The encapsulation efficiency is 88% and the drug loading capacity is 5.5%, respectively. In vitro, SH-NPs significantly enhanced cellular uptake in HaCaT cells. In vivo, treatment with SH-NPs significantly improved skin structural disorders, epidermal thickening, and collagen fiber reduction, while downregulating the expression of MMP-2 and MMP-9. Furthermore, SH-NPs increased the expression of SOD1 and SOD2, reduced MDA levels, and decreased the expression of TNF-α, IL-1β, and NO. In conclusion, SH-NPs attenuated PM2.5-induced skin toxicity via enhanced antioxidant, anti-inflammatory, and anti-degradation mechanisms, offering a novel strategy to boost shikonin bioavailability and prevent PM2.5-related skin damage. Full article
(This article belongs to the Section Health Outcomes of Antioxidants and Oxidative Stress)
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14 pages, 1927 KB  
Article
Comparative Study on Leaf Functional Traits and Environmental Adaptability of Seedlings of the Endangered Plants Ormosia olivacea, Ormosia pachycarpa, and Ormosia sericeolucida
by Juntong Yan, Guohua He, Xi Li, Shuo Feng, Yingying Wu, Rong Zou and Jianmin Tang
Agronomy 2025, 15(11), 2512; https://doi.org/10.3390/agronomy15112512 - 29 Oct 2025
Viewed by 301
Abstract
To investigate the photosynthetic characteristics and leaf anatomical structures of seedlings from the endangered plants Ormosia olivacea, Ormosia pachycarpa, and Ormosia sericeolucida, this study aimed to elucidate the influence of leaf structure on photosynthetic traits and light requirements among these [...] Read more.
To investigate the photosynthetic characteristics and leaf anatomical structures of seedlings from the endangered plants Ormosia olivacea, Ormosia pachycarpa, and Ormosia sericeolucida, this study aimed to elucidate the influence of leaf structure on photosynthetic traits and light requirements among these three Ormosia species, thereby providing reference for their introduction and cultivation. This study measured the light response curves, CO2 response curves, leaf epidermal and anatomical characteristics, and photosynthetic pigment content of the three Ormosia species. Results indicate: 1. All three species exhibit photophilic tendencies, with Ormosia olivacea demonstrating the highest photosynthetic capacity, achieving a maximum net photosynthetic rate (Pmax) of 1.9062 mol m−2 s−1. Ormosia pachycarpa exhibited the highest potential maximum net photosynthetic rate (Amax), demonstrating superior CO2 utilisation capacity. The Amax values for all three species were significantly higher than their Pmax values. 2. Among the three Ormosia species, Ormosia sericeolucida exhibited the thickest leaf structure, with palisade tissue thickness ordered as follows: Ormosia sericeolucida > Ormosia pachycarpa > Ormosia olivacea. 3. Stomata were present on the lower epidermis of all three species. Ormosia sericeolucida possessed the largest individual stomatal area, while Ormosia olivacea exhibited the highest stomatal density. 4. The chlorophyll a content (Chl a) of all three Ormosia species exceeded their chlorophyll b content (Chl b), indicating they are photophilic plants. Ormosia sericeolucida exhibited higher chlorophyll a (Chl a), chlorophyll b (Chl b), and total chlorophyll (Chl) contents than both Ormosia olivacea and Ormosia pachycarpa. Ormosia olivacea possessed the highest carotenoid content (Car). In summary, Ormosia pachycarpa exhibited the highest potential maximum net photosynthetic rate (Amax), demonstrating the strongest CO2 utilisation capacity, followed by Ormosia olivacea, with Ormosia sericeolucida showing the lowest. Appropriately increasing CO2 levels in cultivation sites would benefit photosynthesis and material accumulation in all three Ormosia species, promoting robust growth. Full article
(This article belongs to the Section Plant-Crop Biology and Biochemistry)
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14 pages, 1627 KB  
Article
Molecular Subtypes and Survival Patterns in Female Breast Cancer: Insights from a 12-Year Cohort
by Ionut Marcel Cobec, Ingolf Juhasz-Böss, Peter Seropian, Sarah Huwer, Vlad Bogdan Varzaru, Andreas Rempen and Aurica Elisabeta Moatar
Medicina 2025, 61(10), 1858; https://doi.org/10.3390/medicina61101858 - 16 Oct 2025
Viewed by 431
Abstract
Background and Objectives: Breast cancer is one of the most common cancers in women and the most common cause of cancer death. Hormone receptors, specifically the estrogen receptor (ER) and progesterone receptor (PR), as well as human epidermal growth factor receptor-2 (Her2), are [...] Read more.
Background and Objectives: Breast cancer is one of the most common cancers in women and the most common cause of cancer death. Hormone receptors, specifically the estrogen receptor (ER) and progesterone receptor (PR), as well as human epidermal growth factor receptor-2 (Her2), are tumor-specific markers used to guide breast cancer therapy. The purpose of this study is to evaluate the impact of tumor biology, including ER, PR, and Her2 expression, on survival in female breast cancer. Materials and Methods: This retrospective cohort study represents an analysis of 2016 female breast cancer cases using anonymized data. We reviewed cases of female breast cancer diagnosed from 1 January 2010 to 31 December 2021, in the Clinic of Obstetrics and Gynecology, Diakoneo Diak Klinikum Schwäbisch Hall, Germany. Data on clinical, pathology, immunohistochemistry, and follow-up characteristics were retrieved from the clinic’s database. To interpret the data, we used the software IBM SPSS Statistics 20, and, to account for multiple comparisons, we used a Bonferroni-adjusted significance level of 0.004. In the survival analysis, the Kaplan–Meier method and the log-rank test of equality of survival distributions were applied. Results: Among 2016 female breast cancer cases, 84.5% (1703/2016) were hormone receptor (HR)-positive. The 5-year overall survival was 0.873 (95% CI (0.851, 0.895); 99.6% CI (0.841, 0.905)) for HR-positive patients and 0.760 (95% CI (0.713, 0.807); 99.6% CI (0.691, 0.829)) for HR-negative patients (p < 0.001). Statistically significant differences were observed among HR+/HER2+, HR+/HER2−, HR−/HER2+, and triple-negative subtypes (p = 0.003). When comparing survival distributions based solely on HER2 expression (positive vs. negative), no statistically significant difference was observed (p = 0.29). Conclusions: Statistically significant differences in unadjusted overall survival distributions were observed among breast cancer molecular subtypes. HR-positive breast cancers demonstrated better overall survival than HR-negative cancers, while no statistically significant difference in unadjusted survival was observed between HER2-positive and HER2-negative groups. Full article
(This article belongs to the Special Issue New Developments in Diagnosis and Management of Breast Cancer)
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24 pages, 1198 KB  
Article
A Comprehensive Analysis of Adverse Events Associated with HER2 Inhibitors Approved for Breast Cancer Using the FDA Adverse Event Report System (FAERS)
by Airi Yajima and Yoshihiro Uesawa
Pharmaceuticals 2025, 18(10), 1510; https://doi.org/10.3390/ph18101510 - 8 Oct 2025
Viewed by 793
Abstract
Background/Objectives: Human epidermal growth factor receptor 2 (HER2) inhibitors have markedly improved outcomes in patients with HER2-positive breast cancer. Clinical treatment often involves the sequential or combined use of multiple HER2 inhibitors, making it essential to clarify their distinct adverse event (AE) profiles. [...] Read more.
Background/Objectives: Human epidermal growth factor receptor 2 (HER2) inhibitors have markedly improved outcomes in patients with HER2-positive breast cancer. Clinical treatment often involves the sequential or combined use of multiple HER2 inhibitors, making it essential to clarify their distinct adverse event (AE) profiles. However, AE trends remain insufficiently understood. This study aimed to comprehensively analyze characteristic AEs associated with HER2 inhibitors. Methods: Using the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS, January 2004–September 2024), we conducted disproportionality analyses of AEs associated with HER2 inhibitors approved for breast cancer. Based on the natural logarithm of the reporting odds ratio (lnROR), hierarchical cluster analysis and principal component analysis (PCA) were performed. Results: Disproportionality analysis treating HER2 inhibitors as a single group identified several signals, with hair disorder (ROR 39.93 [95% CI: 37.68–42.32]) as a representative example. Hierarchical clustering showed that monoclonal antibodies (mAbs) and tyrosine kinase inhibitors (TKIs) diverged early in the dendrogram, and clusters broadly corresponded to pharmacological classes. The cluster of hair-related AEs closely corresponded to mAbs. PCA indicated that the first component reflected AE occurrence risk (R2 = 0.655, p < 0.0001), the second component distinguished mAbs from TKIs (tucatinib: r = 0.667; trastuzumab: r = −0.567), and the third component separated molecular targeted agents from antibody–drug conjugates (neratinib: r = 0.521; T-DXd: r = −0.440). Conclusions: FAERS-based analyses enabled visualization of the distinct AE profiles of HER2 inhibitors. These findings may support safe drug selection, risk stratification, and improved AE management strategies. Full article
(This article belongs to the Section Pharmacology)
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17 pages, 762 KB  
Article
Real-World Prevalence, Treatment Patterns, and Economic Impact of EGFR- and ALK-Targeted Therapies in Non-Small Cell Lung Cancer: A Nationwide Analysis from Greece
by George Gourzoulidis, Catherine Kastanioti, George Mavridoglou, Theodore Kotsilieris, Anastasios Tsolakidis, Konstantinos Mathioudakis, Dikaios Voudigaris and Charalampos Tzanetakos
Curr. Oncol. 2025, 32(10), 542; https://doi.org/10.3390/curroncol32100542 - 27 Sep 2025
Viewed by 848
Abstract
Objectives: To determine the prescribing prevalence of epidermal growth factor receptor (EGFR)- and anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) patients in Greece and examine patterns of first-line tyrosine kinase inhibitor (TKI) utilization and associated treatment costs using nationwide real-world data. [...] Read more.
Objectives: To determine the prescribing prevalence of epidermal growth factor receptor (EGFR)- and anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) patients in Greece and examine patterns of first-line tyrosine kinase inhibitor (TKI) utilization and associated treatment costs using nationwide real-world data. Methods: A retrospective analysis of the national e-prescription database was performed, identifying patients initiating first-line treatment (FLT) for EGFR- or ALK-positive NSCLC between 1 January 2020 and 31 December 2022. Demographic characteristics, prescribing prevalence data, drug utilization patterns, total annual drug expenditures, and per patient treatment costs were assessed. All statistical analyses were performed using the statistical software SPSS-v.29. Results: Overall, 1188 EGFR-positive (mean age of 70.93 ± 11.6) and 246 (mean age of 64.26 ± 12.6) ALK-positive NSCLC patients initiated FLT during the three-year study period. EGFR mutations were slightly more common in females (53%), peaking in the 70–79 age group (35%). ALK mutations were also more common among females (52%), particularly within the 60–79 age group. In EGFR-positive patients, osimertinib usage markedly increased from 41% in 2020 to 63% in 2022, primarily displacing afatinib (from 32% to 22%) and erlotinib (from 24% to 14%), with gefitinib prescriptions falling below 2%. Among ALK-positive patients, crizotinib utilization declined significantly from 60% to 16%, whereas alectinib increased to 59% by 2022. Annual EGFR-related total drug expenditures remained stable (€11.5 million in 2020 vs. €11.9 million in 2022), driven primarily by increasing osimertinib usage. Similarly, ALK-related annual drug expenditures showed stability, with costs predominantly attributed to rising alectinib utilization. Conclusions: This nationwide analysis highlights the rapid adoption of second- and third-generation TKIs for EGFR- and ALK-positive NSCLC in Greece, reflecting evolving clinical practice patterns. Although the target patient populations are relatively small, the associated economic burden is considerable. To ensure long-term sustainability of the Greek healthcare system, policymakers should critically assess the cost-effectiveness of these innovative therapies and align resource allocation with value-based care principles. Full article
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16 pages, 961 KB  
Review
Long Non-Coding RNAs in Psoriasis: A Comprehensive Review of Expression Profiles, Mechanistic Insights, Genetic Associations, and Their Clinical Implications
by Judit Danis and Márta Széll
Non-Coding RNA 2025, 11(5), 69; https://doi.org/10.3390/ncrna11050069 - 19 Sep 2025
Viewed by 756
Abstract
Psoriasis is a chronic inflammatory skin disorder affecting approximately 2% of the global population, characterized by abnormal keratinocyte proliferation and dysregulated immune responses. This review examines the emerging role of long non-coding RNAs (lncRNAs) in psoriasis pathogenesis, highlighting their significance as regulatory molecules [...] Read more.
Psoriasis is a chronic inflammatory skin disorder affecting approximately 2% of the global population, characterized by abnormal keratinocyte proliferation and dysregulated immune responses. This review examines the emerging role of long non-coding RNAs (lncRNAs) in psoriasis pathogenesis, highlighting their significance as regulatory molecules in disease initiation, progression, and chronicity. LncRNAs demonstrate distinct expression patterns in psoriatic lesions, with upregulated transcripts such as MALAT1, XIST, MIR31HG, and HOTAIR promoting keratinocyte hyperproliferation, inhibiting apoptosis, and amplifying inflammatory cascades through mechanisms including microRNA sponging and transcription factor modulation. These molecules primarily target key signaling pathways including NF-κB, STAT3, and PI3K/AKT. Conversely, downregulated lncRNAs like NEAT1, MEG3, and PRINS normally function as tumor suppressor molecules that maintain epidermal homeostasis through pro-apoptotic and anti-inflammatory mechanisms. Their reduced expression contributes to the pathological hyperproliferative phenotype characteristic of psoriatic skin. Importantly, genetic variants within lncRNA loci have been identified as significant contributors to psoriasis susceptibility and treatment responses across different populations. Single- nucleotide polymorphisms in genes such as TRAF3IP2-AS1, HOTAIR, and CDKN2B-AS1 demonstrate population-specific associations with disease risk and therapeutic outcomes, suggesting their potential utility as pharmacogenomic markers. The complex regulatory networks involving lncRNAs provide new insights into psoriasis pathogenesis and offer promising avenues for personalized treatment strategies. Integration of lncRNA profiling into clinical practice may enhance our understanding of disease heterogeneity and improve therapeutic outcomes for psoriatic patients. Full article
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14 pages, 1154 KB  
Article
The Clinical Characteristics, Treatment, and Prognosis of Lung Cancer in Young Patients in the New Era of Cancer Treatment: A Retrospective and Comprehensive Analysis
by Xiaoyi Feng, Shengjie Li, Siyuan Yu, Yunxin Liu, Zhanxian Peng, Haoran Zhang, Xiaoxing Gao, Xiaoyan Liu, Minjiang Chen, Jing Zhao, Wei Zhong, Yan Xu and Mengzhao Wang
Curr. Oncol. 2025, 32(9), 489; https://doi.org/10.3390/curroncol32090489 - 31 Aug 2025
Cited by 1 | Viewed by 1261
Abstract
Background: This study was aimed to comprehensively investigate the clinical and molecular characteristics, treatments, and outcomes of young patients with lung cancer in the new era of cancer treatment. Methods: Clinical data from patients aged 18 to 45 with lung cancer, treated at [...] Read more.
Background: This study was aimed to comprehensively investigate the clinical and molecular characteristics, treatments, and outcomes of young patients with lung cancer in the new era of cancer treatment. Methods: Clinical data from patients aged 18 to 45 with lung cancer, treated at our hospital from January 2014 through January 2024, were systematically collected and analyzed. Results: This study enrolled a total of 343 patients, with a predominance of females, never-smokers, and those diagnosed at an advanced stage. Adenocarcinoma was the most common histology (72.0%), and rare tumors could also be seen in young patients, such as pulmonary sarcomatoid carcinoma and pulmonary mucoepidermoid carcinoma. The mutation rate of the epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) in NSCLC patients were 35.9% (111/309) and 14.2% (44/309), respectively. PD-L1 expression was assessed in 55 patients, with 14 showing high expression (≥50%) and 24 showing negative expression (<1%). The median overall survival (mOS) for the entire cohort was 80.2 months, with a 5-year survival rate of 55.7%. For patients with stage I, II, and III disease, the mOS had not yet been reached, whereas the mOS for stage IV patients was 39.7 months. Targeted therapy, particularly second-generation ALK tyrosine kinase inhibitors (TKIs), significantly improved the prognosis of patients with driver gene mutations. Chemotherapy combined with immunotherapy was beneficial for patients with progressive disease or driver gene negativity in NSCLC and was associated with improved OS in small cell lung cancer (SCLC). Female, family history of lung cancer, positive driver genes, and first-line use of second-generation ALK-TKIs are independent prognostic factors in young patients with advanced NSCLC. Conclusions: Our findings highlight the importance of early diagnosis, targeted therapy, and immunotherapy in improving outcomes for young patients with lung cancer. Full article
(This article belongs to the Section Thoracic Oncology)
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24 pages, 3632 KB  
Article
Adaptation of Plants to UV-B Radiation with Altitude in Tuha Basin: Synergistic Regulation of Epidermal Structure, Secondary Metabolites, and Organic Element Allocation
by Xiao-Min Wang, Guo-Qiang Zhao, Jie Chen, Fang-Zheng Jing, Li Li, Yu-Ying Wang, Ping Ma, Yu-Hang Wu, Shi-Jian Xu and Wen-Liang He
Life 2025, 15(9), 1375; https://doi.org/10.3390/life15091375 - 29 Aug 2025
Viewed by 915
Abstract
Ultraviolet B (UV-B) radiation is a key environmental factor that limits plant growth and development. High UV-B intensity is a typical environmental feature in Turpan-Hami (Tuha) Basin in Xinjiang, China. In this study, the altitude-dependent UV-B adaptation strategies of plants in Tuha Basin [...] Read more.
Ultraviolet B (UV-B) radiation is a key environmental factor that limits plant growth and development. High UV-B intensity is a typical environmental feature in Turpan-Hami (Tuha) Basin in Xinjiang, China. In this study, the altitude-dependent UV-B adaptation strategies of plants in Tuha Basin were analyzed. Chlorophyll (Chl) and flavonoid (Fla) play an important role in absorbing UV-B radiation, scavenging free radicals, and maintaining photosynthetic performance under UV-B stress. Principal component analysis indicated that the total chlorophyll (Chl t), Chl a, Chl b, and Fla contents and the Chl a/Chl b ratio are important indicators for evaluating plant tolerance to UV-B. Noticeably, with increased altitudes, the roles of Chl b, Chl a/Chl b, and Fla become markedly significant. The characteristics of stomata, epidermal hair, and wax layer are closely correlated with the UV-B amount that reaches leaves. Epidermal hair density and cuticle thickness in leaves decreased with increased altitudes, whereas hydrogen oxide (H2O2) was significantly accumulated, but superoxide anion (O2) remained unchanged. High altitude significantly increased the stomatal apparatus area, density and specific leaf area. Moreover, plants without epidermal hair had a larger stomatal apparatus area compared with plants with epidermal hair. However, the presence or absence of epidermal hair had no effect on cuticle thickness, H2O2 and O2 levels. The carbon (C), nitrogen (N), and hydrogen (H) contents were high in plant leaves at high altitude, but the sulfur (S) content and C/N ratio were low. Taken together, plants in Tuha Basin could cope with UV-B radiation by synergistically regulating epidermal structures and synthesis of secondary metabolites. Meanwhile, these plants could further allocate and reconstruct organic elements to optimize their resource distribution in adaptation to UV-B radiation with different altitudes. Full article
(This article belongs to the Special Issue Physiological Responses and Adaptation Mechanisms of Plants to Stress)
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