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16 pages, 3102 KiB  
Article
The Effect of Mild Exercise in the Chemotherapy Room on the Anxiety Level of Cancer Patients: A Prospective Observational Paired Cohort Study
by Christina Mavrogiannopoulou, Georgios Papastratigakis, Emmanouela Koutoulaki, Panagiotis Vardakis, Georgios Stefanakis, Athanasios Kourtsilidis, Kostantinos Lasithiotakis, Alexandra Papaioannou and Vasileia Nyktari
J. Clin. Med. 2025, 14(15), 5591; https://doi.org/10.3390/jcm14155591 - 7 Aug 2025
Abstract
Background/Objectives: Cancer represents a significant health challenge, with high mortality and morbidity rates. Its diagnosis often triggers chronic stress, adversely affecting patient outcomes. Exercise has emerged as complementary therapy, enhancing treatment adherence and mitigating the side effects of chemotherapy. This study examines the [...] Read more.
Background/Objectives: Cancer represents a significant health challenge, with high mortality and morbidity rates. Its diagnosis often triggers chronic stress, adversely affecting patient outcomes. Exercise has emerged as complementary therapy, enhancing treatment adherence and mitigating the side effects of chemotherapy. This study examines the effects of mild exercise during chemotherapy on patient anxiety. Methods: This prospective paired cohort study was conducted in the General Oncology Hospital of Kifisia “Agioi Anargyroi” in Athens, Greece. Adult cancer patients undergoing chemotherapy participated, excluding those with cognitive, hearing, or motor impairments, those who experienced side effects, or those who declined consent. Anxiety was measured before and after a 20-minute exercise routine performed during chemotherapy, using the Greek-translated State–Trait Anxiety Inventory (STAI). The exercise regimen included warm-up, full-body stretching, and cool-down exercises. Pre- and post-exercise scores were analyzed using the Wilcoxon signed-rank test. Results: Forty-five patients (20 women, 25 men; mean age 69.02 ± 10.62 years) with various cancer backgrounds participated. Pre-intervention anxiety levels were in the borderline “moderate” range, dropping post-exercise to the “low” range. Mean STAI scores decreased from 37.73 ± 13.33 to 32.00 ± 14.22 (p < 0.0001), with a medium-large effect size (Cohen’s d for paired samples = −0.646). No significant correlation was found between age and anxiety scores. Discussion: This study found a significant short-term reduction in anxiety, suggesting that incorporating mild exercise during chemotherapy may help in alleviating patient stress. The medium-to-large effect size supports the potential for meaningful short-term benefits. Conclusions: Incorporating mild exercise during chemotherapy may help reduce anxiety and psychological burden. These findings underscore the need for more comprehensive research in larger, more diverse populations to better understand the benefits of incorporating mild exercise during chemotherapy. Full article
(This article belongs to the Section Oncology)
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28 pages, 3469 KiB  
Review
Prostate Cancer Treatments and Their Effects on Male Fertility: Mechanisms and Mitigation Strategies
by Aris Kaltsas, Nikolaos Razos, Zisis Kratiras, Dimitrios Deligiannis, Marios Stavropoulos, Konstantinos Adamos, Athanasios Zachariou, Fotios Dimitriadis, Nikolaos Sofikitis and Michael Chrisofos
J. Pers. Med. 2025, 15(8), 360; https://doi.org/10.3390/jpm15080360 - 7 Aug 2025
Abstract
Prostate cancer (PCa) is the second most frequently diagnosed malignancy in men worldwide. Although traditionally considered a disease of older men, the incidence of early-onset PCa (diagnosis < 55 years) is steadily rising. Advances in screening and therapy have significantly improved survival, creating [...] Read more.
Prostate cancer (PCa) is the second most frequently diagnosed malignancy in men worldwide. Although traditionally considered a disease of older men, the incidence of early-onset PCa (diagnosis < 55 years) is steadily rising. Advances in screening and therapy have significantly improved survival, creating a growing cohort of younger survivors for whom post-treatment quality of life—notably reproductive function—is paramount. Curative treatments such as radical prostatectomy, pelvic radiotherapy, androgen-deprivation therapy (ADT), and chemotherapy often cause irreversible infertility via multiple mechanisms, including surgical disruption of the ejaculatory tract, endocrine suppression of spermatogenesis, direct gonadotoxic injury to the testes, and oxidative sperm DNA damage. Despite these risks, fertility preservation is frequently overlooked in pre-treatment counseling, leaving many patients unaware of their options. This narrative review synthesizes current evidence on how PCa therapies impact male fertility, elucidates the molecular and physiological mechanisms of iatrogenic infertility, and evaluates both established and emerging strategies for fertility preservation and restoration. Key interventions covered include sperm cryopreservation, microsurgical testicular sperm extraction (TESE), and assisted reproductive technologies (ART). Psychosocial factors influencing decision-making, novel biomarkers predictive of post-treatment spermatogenic recovery, and long-term offspring outcomes are also examined. The review underscores the urgent need for timely, multidisciplinary fertility consultation as a routine component of PCa care. As PCa increasingly affects men in their reproductive years, proactively integrating preservation into standard oncologic practice should become a standard survivorship priority. Full article
(This article belongs to the Special Issue Clinical Advances in Male Genitourinary and Sexual Health)
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14 pages, 1754 KiB  
Article
Dissecting Tumor Heterogeneity by Liquid Biopsy—A Comparative Analysis of Post-Mortem Tissue and Pre-Mortem Liquid Biopsies in Solid Neoplasias
by Tatiana Mögele, Kathrin Hildebrand, Aziz Sultan, Sebastian Sommer, Lukas Rentschler, Maria Kling, Irmengard Sax, Matthias Schlesner, Bruno Märkl, Martin Trepel, Maximilian Schmutz and Rainer Claus
Int. J. Mol. Sci. 2025, 26(15), 7614; https://doi.org/10.3390/ijms26157614 - 6 Aug 2025
Abstract
Tumor heterogeneity encompasses genetic, epigenetic, and phenotypic diversity, impacting treatment response and resistance. Spatial heterogeneity occurs both inter- and intra-lesionally, while temporal heterogeneity results from clonal evolution. High-throughput technologies like next-generation sequencing (NGS) enhance tumor characterization, but conventional biopsies still do not adequately [...] Read more.
Tumor heterogeneity encompasses genetic, epigenetic, and phenotypic diversity, impacting treatment response and resistance. Spatial heterogeneity occurs both inter- and intra-lesionally, while temporal heterogeneity results from clonal evolution. High-throughput technologies like next-generation sequencing (NGS) enhance tumor characterization, but conventional biopsies still do not adequately capture genetic heterogeneity. Liquid biopsy (LBx), analyzing circulating tumor DNA (ctDNA), provides a minimally invasive alternative, offering real-time tumor evolution insights and identifying resistance mutations overlooked by tissue biopsies. This study evaluates the capability of LBx to capture tumor heterogeneity by comparing genetic profiles from multiple metastatic lesions and LBx samples. Eight patients from the Augsburger Longitudinal Plasma Study with various types of cancer provided 56 postmortem tissue samples, which were compared against pre-mortem LBx-derived circulating-free DNA sequenced by NGS. Tissue analyses revealed significant mutational diversity (4–12 mutations per patient, VAFs: 1.5–71.4%), with distinct intra- and inter-lesional heterogeneity. LBx identified 51 variants (4–17 per patient, VAFs: 0.2–31.1%), which overlapped with mutations from the tissue samples by 33–92%. Notably, 22 tissue variants were absent in LBx, whereas 18 LBx-exclusive variants were detected (VAFs: 0.2–2.8%). LBx effectively captures tumor heterogeneity, but should be used in conjunction with tissue biopsies for comprehensive genetic profiling. Full article
(This article belongs to the Special Issue Liquid Biopsies in Oncology—3rd Edition)
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17 pages, 4116 KiB  
Article
A Bifunctional Anti-PD-1/TGF-β Fusion Antibody Restores Antitumour Immunity and Remodels the Tumour Microenvironment
by Lidi Nan, Yuting Qin, Xiao Huang, Mingzhu Pan, Xiaomu Wang, Yanqing Lv, Annette Sorensen, Xiaoqiang Kang, Hong Ling and Juan Zhang
Int. J. Mol. Sci. 2025, 26(15), 7567; https://doi.org/10.3390/ijms26157567 - 5 Aug 2025
Abstract
Although PD-1/PD-L1 inhibitors have transformed cancer immunotherapy, a substantial proportion of patients derive no clinical benefit due to resistance driven by the tumour microenvironment (TME). Transforming growth factor-β (TGF-β) is a key immunosuppressive cytokine implicated in this resistance. Several bifunctional antibodies that co-target [...] Read more.
Although PD-1/PD-L1 inhibitors have transformed cancer immunotherapy, a substantial proportion of patients derive no clinical benefit due to resistance driven by the tumour microenvironment (TME). Transforming growth factor-β (TGF-β) is a key immunosuppressive cytokine implicated in this resistance. Several bifunctional antibodies that co-target PD-1 and TGF-β signalling have entered clinical trials and shown encouraging efficacy, but the mechanistic basis of their synergy is not fully understood. Here, we engineered 015s, a bifunctional fusion antibody that simultaneously targets murine PD-1 and TGF-β and evaluated its antitumour efficacy and mechanistic impact in pre-clinical models. Antibody 015s exhibited high affinity, dual target binding, and the effective inhibition of PD-1 and TGF-β signalling. In vivo, 015s significantly suppressed tumour growth compared with anti-mPD-1 or TGF-β receptor II (TGF-βRII) monotherapy. When combined with the CD24-targeted ADC, 015s produced even greater antitumour activity and achieved complete tumour regression. Mechanistic studies demonstrated that 015s significantly reduced tumour cell migration and invasion, reversed epithelial–mesenchymal transition (EMT), decreased microvascular density, and attenuated collagen deposition within the TME. Antibody 015s also decreased bioactive TGF-β1 and increased intratumoural IFN-γ, creating a more immunostimulatory milieu. These findings support further development of PD-1/TGF-β bifunctional antibodies for cancers with high TGF-β activity or limited response to immune checkpoint blockade. Full article
(This article belongs to the Section Molecular Immunology)
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16 pages, 2030 KiB  
Article
Myocardial Strain Measurements Obtained with Fast-Strain-Encoded Cardiac Magnetic Resonance for the Risk Prediction and Early Detection of Chemotherapy-Related Cardiotoxicity Compared to Left Ventricular Ejection Fraction
by Daniel Lenihan, James Whayne, Farouk Osman, Rafael Rivero, Moritz Montenbruck, Arne Kristian Schwarz, Sebastian Kelle, Pia Wülfing, Susan Dent, Florian Andre, Norbert Frey, Grigorios Korosoglou and Henning Steen
Diagnostics 2025, 15(15), 1948; https://doi.org/10.3390/diagnostics15151948 - 3 Aug 2025
Viewed by 267
Abstract
Background: Breast and hematological cancer treatments, especially with anthracyclines, have been shown to be associated with an increased risk of cardiotoxicity (CTX). An accurate prediction of cardiotoxicity risk and early detection of myocardial injury may allow for effective cardioprotection to be instituted and [...] Read more.
Background: Breast and hematological cancer treatments, especially with anthracyclines, have been shown to be associated with an increased risk of cardiotoxicity (CTX). An accurate prediction of cardiotoxicity risk and early detection of myocardial injury may allow for effective cardioprotection to be instituted and tailored to reverse cardiac dysfunction and prevent the discontinuation of essential cancer treatments. Objectives: The PRoactive Evaluation of Function to Evade Cardio Toxicity (PREFECT) study sought to evaluate the ability of fast-strain-encoded (F-SENC) cardiac magnetic resonance imaging (CMR) and 2D echocardiography (2D Echo) to stratify patients at risk of CTX prior to initiating cancer treatment, detect early signs of cardiac dysfunction, including subclinical CTX (sub-CTX) and CTX, and monitor for recovery (REC) during cardioprotective therapy. Methods: Fifty-nine patients with breast cancer or lymphoma were prospectively monitored for CTX with F-SENC CMR and 2D Echo over at least 1 year for evidence of cardiac dysfunction during anthracycline based chemotherapy. F-SENC CMR also monitored myocardial deformation in 37 left ventricular (LV) segments to obtain a MyoHealth risk score based on both longitudinal and circumferential strain. Sub-CTX and CTX were classified based on pre-specified cardiotoxicity definitions. Results: CTX was observed in 9/59 (15%) and sub-CTX in 24/59 (41%) patients undergoing chemotherapy. F-SENC CMR parameters at baseline predicted CTX with a lower LVEF (57 ± 5% vs. 61 ± 5% for all, p = 0.05), as well as a lower MyoHealth (70 ± 9 vs. 79 ± 11 for all, p = 0.004) and a worse global circumferential strain (GCS) (−18 ± 1 vs. −20 ± 1 for all, p < 0.001). Pre-chemotherapy MyoHealth had a higher accuracy in predicting the development of CTX compared to CMR LVEF and 2D Echo LVEF (AUC = 0.85, 0.69, and 0.57, respectively). The 2D Echo parameters on baseline imaging did not stratify CTX risk. F-SENC CMR obtained good or excellent images in 320/322 (99.4%) scans. During cancer treatment, MyoHealth had a high accuracy of detecting sub-CTX or CTX (AUC = 0.950), and the highest log likelihood ratio (indicating a higher probability of detecting CTX) followed by F-SENC GLS and F-SENC GCS. CMR LVEF and CMR LV stroke volume index (LVSVI) also significantly worsened in patients developing CTX during cancer treatment. Conclusions: F-SENC CMR provided a reliable and accurate assessment of myocardial function during anthracycline-based chemotherapy, and demonstrated accurate early detection of CTX. In addition, MyoHealth allows for the robust identification of patients at risk for CTX prior to treatment with higher accuracy than LVEF. Full article
(This article belongs to the Special Issue New Perspectives in Cardiac Imaging)
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19 pages, 3468 KiB  
Article
Fine-Tuning Models for Histopathological Classification of Colorectal Cancer
by Houda Saif ALGhafri and Chia S. Lim
Diagnostics 2025, 15(15), 1947; https://doi.org/10.3390/diagnostics15151947 - 3 Aug 2025
Viewed by 160
Abstract
Background/Objectives: This study aims to design and evaluate transfer learning strategies that fine-tune multiple pre-trained convolutional neural network architectures based on their characteristics to improve the accuracy and generalizability of colorectal cancer histopathological image classification. Methods: The application of transfer learning with pre-trained [...] Read more.
Background/Objectives: This study aims to design and evaluate transfer learning strategies that fine-tune multiple pre-trained convolutional neural network architectures based on their characteristics to improve the accuracy and generalizability of colorectal cancer histopathological image classification. Methods: The application of transfer learning with pre-trained models on specialized and multiple datasets is proposed, where the proposed models, CRCHistoDense, CRCHistoIncep, and CRCHistoXcep, are algorithmically fine-tuned at varying depths to improve the performance of colorectal cancer classification. These models were applied to datasets of 10,613 images from public and private repositories, external sources, and unseen data. To validate the models’ decision-making and improve transparency, we integrated Grad-CAM to provide visual explanations that influence classification decisions. Results and Conclusions: On average across all datasets, CRCHistoDense, CRCHistoIncep, and CRCHistoXcep achieved test accuracies of 99.34%, 99.48%, and 99.45%, respectively, highlighting the effectiveness of fine-tuning in improving classification performance and generalization. Statistical methods, including paired t-tests, ANOVA, and the Kruskal–Wallis test, confirmed significant improvements in the proposed methods’ performance, with p-values below 0.05. These findings demonstrate that fine-tuning based on the characteristics of CNN’s architecture enhances colorectal cancer classification in histopathology, thereby improving the diagnostic potential of deep learning models. Full article
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17 pages, 516 KiB  
Article
Incidence and Predictive Factors of Acute Kidney Injury After Major Hepatectomy: Implications for Patient Management in Era of Enhanced Recovery After Surgery (ERAS) Protocols
by Henri Mingaud, Jean Manuel de Guibert, Jonathan Garnier, Laurent Chow-Chine, Frederic Gonzalez, Magali Bisbal, Jurgita Alisauskaite, Antoine Sannini, Marc Léone, Marie Tezier, Maxime Tourret, Sylvie Cambon, Jacques Ewald, Camille Pouliquen, Lam Nguyen Duong, Florence Ettori, Olivier Turrini, Marion Faucher and Djamel Mokart
J. Clin. Med. 2025, 14(15), 5452; https://doi.org/10.3390/jcm14155452 - 2 Aug 2025
Viewed by 360
Abstract
Background: Acute kidney injury (AKI) frequently occurs following major liver resection, adversely affecting both short- and long-term outcomes. This study aimed to determine the incidence of AKI post-hepatectomy and identify relevant pre- and intraoperative risk factors. Our secondary objectives were to develop [...] Read more.
Background: Acute kidney injury (AKI) frequently occurs following major liver resection, adversely affecting both short- and long-term outcomes. This study aimed to determine the incidence of AKI post-hepatectomy and identify relevant pre- and intraoperative risk factors. Our secondary objectives were to develop a predictive score for postoperative AKI and assess the associations between AKI, chronic kidney disease (CKD), and 1-year mortality. Methods: This was a retrospective study in a cancer referral center in Marseille, France, from 2018 to 2022. Results: Among 169 patients, 55 (32.5%) experienced AKI. Multivariate analysis revealed several independent risk factors for postoperative AKI, including age, body mass index, the use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, time to liver resection, intraoperative shock, and bile duct reconstruction. Neoadjuvant chemotherapy was protective. The AKIMEBO score was developed, with a threshold of ≥15.6, demonstrating a sensitivity of 89.5%, specificity of 76.4%, positive predictive value of 61.8%, and negative predictive value of 94.4%. AKI was associated with increased postoperative morbidity and one-year mortality following major hepatectomy. Conclusion: AKI is a common complication post-hepatectomy. Factors such as time to liver resection and intraoperative shock management present potential clinical intervention points. The AKIMEBO score can provide a valuable tool for postoperative risk stratification. Full article
(This article belongs to the Section Gastroenterology & Hepatopancreatobiliary Medicine)
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18 pages, 929 KiB  
Review
From Hypoxia to Bone: Reprogramming the Prostate Cancer Metastatic Cascade
by Melissa Santos, Sarah Koushyar, Dafydd Alwyn Dart and Pinar Uysal-Onganer
Int. J. Mol. Sci. 2025, 26(15), 7452; https://doi.org/10.3390/ijms26157452 - 1 Aug 2025
Viewed by 354
Abstract
Bone is the most frequent site of distant metastasis in advanced prostate cancer (PCa), contributing substantially to patient morbidity and mortality. Hypoxia, a defining feature of the solid tumour microenvironment, plays a pivotal role in driving bone-tropic progression by promoting epithelial-to-mesenchymal transition (EMT), [...] Read more.
Bone is the most frequent site of distant metastasis in advanced prostate cancer (PCa), contributing substantially to patient morbidity and mortality. Hypoxia, a defining feature of the solid tumour microenvironment, plays a pivotal role in driving bone-tropic progression by promoting epithelial-to-mesenchymal transition (EMT), cancer stemness, extracellular matrix (ECM) remodelling, and activation of key signalling pathways such as Wingless/Integrated (Wnt) Wnt/β-catenin and PI3K/Akt. Hypoxia also enhances the secretion of extracellular vesicles (EVs), enriched with pro-metastatic cargos, and upregulates bone-homing molecules including CXCR4, integrins, and PIM kinases, fostering pre-metastatic niche formation and skeletal colonisation. In this review, we analysed current evidence on how hypoxia orchestrates PCa dissemination to bone, focusing on the molecular crosstalk between HIF signalling, Wnt activation, EV-mediated communication, and cellular plasticity. We further explore therapeutic strategies targeting hypoxia-related pathways, such as HIF inhibitors, hypoxia-activated prodrugs, and Wnt antagonists, with an emphasis on overcoming therapy resistance in castration-resistant PCa (CRPC). By examining the mechanistic underpinnings of hypoxia-driven bone metastasis, we highlight promising translational avenues for improving patient outcomes in advanced PCa. Full article
(This article belongs to the Special Issue Hypoxia: Molecular Mechanism and Health Effects)
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35 pages, 1395 KiB  
Review
Local Chemotherapy of Skin Pre-Neoplastic Lesions and Malignancies from the Perspective of Current Pharmaceutics
by Nadezhda Ivanova
Pharmaceutics 2025, 17(8), 1009; https://doi.org/10.3390/pharmaceutics17081009 - 1 Aug 2025
Viewed by 470
Abstract
In the preceding and early stages of cancer progression, local drug delivery to pre-cancerous and cancerous skin lesions may be applied as an alternative or supplementary therapy. At present, 5-Fluorouracil, imiquimod, and tirbanibulin creams and ointments have established their place in practice, while [...] Read more.
In the preceding and early stages of cancer progression, local drug delivery to pre-cancerous and cancerous skin lesions may be applied as an alternative or supplementary therapy. At present, 5-Fluorouracil, imiquimod, and tirbanibulin creams and ointments have established their place in practice, while several other active pharmaceutical ingredients (APIs) (e.g., calcipotriol, tretinoin, diclofenac) have been repurposed, used off-label, or are currently being investigated in mono- or combined chemotherapies of skin cancers. Apart from them, dozens to hundreds of therapeutics of natural and synthetic origin are proven to possess anti-tumor activity against melanoma, squamous cell carcinoma (SCC), and other skin cancer types in in vitro studies. Their clinical introduction is most often limited by low skin permeability, challenged targeted drug delivery, insufficient chemical stability, non-selective cytotoxicity, or insufficient safety data. A variety of prodrug and nanotechnological approaches, including vesicular systems, micro- and nanoemulsions, solid lipid nanoparticles, nanostructured lipid carriers, polymeric nanoparticles, and others, offer versatile solutions for overcoming the biophysical barrier function of the skin and the undesirable physicochemical nature of some drug molecules. This review aims to present the most significant aspects and latest achievements on the subject. Full article
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12 pages, 955 KiB  
Article
Single-Center Preliminary Experience Treating Endometrial Cancer Patients with Fiducial Markers
by Francesca Titone, Eugenia Moretti, Alice Poli, Marika Guernieri, Sarah Bassi, Claudio Foti, Martina Arcieri, Gianluca Vullo, Giuseppe Facondo, Marco Trovò, Pantaleo Greco, Gabriella Macchia, Giuseppe Vizzielli and Stefano Restaino
Life 2025, 15(8), 1218; https://doi.org/10.3390/life15081218 - 1 Aug 2025
Viewed by 206
Abstract
Purpose: To present the findings of our preliminary experience using daily image-guided radiotherapy (IGRT) supported by implanted fiducial markers (FMs) in the radiotherapy of the vaginal cuff, in a cohort of post-surgery endometrial cancer patients. Methods: Patients with vaginal cuff cancer [...] Read more.
Purpose: To present the findings of our preliminary experience using daily image-guided radiotherapy (IGRT) supported by implanted fiducial markers (FMs) in the radiotherapy of the vaginal cuff, in a cohort of post-surgery endometrial cancer patients. Methods: Patients with vaginal cuff cancer requiring adjuvant radiation with external beams were enrolled. Five patients underwent radiation therapy targeting the pelvic disease and positive lymph nodes, with doses of 50.4 Gy in twenty-eight fractions and a subsequent stereotactic boost on the vaginal vault at a dose of 5 Gy in a single fraction. One patient was administered 30 Gy in five fractions to the vaginal vault. These patients underwent external beam RT following the implantation of three 0.40 × 10 mm gold fiducial markers (FMs). Our IGRT strategy involved real-time 2D kV image-based monitoring of the fiducial markers during the treatment delivery as a surrogate of the vaginal cuff. To explore the potential role of FMs throughout the treatment process, we analyzed cine movies of the 2D kV-triggered images during delivery, as well as the image registration between pre- and post-treatment CBCT scans and the planning CT (pCT). Each CBCT used to trigger fraction delivery was segmented to define the rectum, bladder, and vaginal cuff. We calculated a standard metric to assess the similarity among the images (Dice index). Results: All the patients completed radiotherapy and experienced good tolerance without any reported acute or long-term toxicity. We did not observe any loss of FMs during or before treatment. A total of twenty CBCTs were analyzed across ten fractions. The observed trend showed a relatively emptier bladder compared to the simulation phase, with the bladder filling during the delivery. This resulted in a final median Dice similarity coefficient (DSC) of 0.90, indicating strong performance. The rectum reproducibility revealed greater variability, negatively affecting the quality of the delivery. Only in two patients, FMs showed intrafractional shift > 5 mm, probably associated with considerable rectal volume changes. Target coverage was preserved due to a safe CTV-to-PTV margin (10 mm). Conclusions: In our preliminary study, CBCT in combination with the use of fiducial markers to guide the delivery proved to be a feasible method for IGRT both before and during the treatment of post-operative gynecological cancer. In particular, this approach seems to be promising in selected patients to facilitate the use of SBRT instead of BRT (brachytherapy), thanks to margin reduction and adaptive strategies to optimize dose delivery while minimizing toxicity. A larger sample of patients is needed to confirm our results. Full article
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26 pages, 4572 KiB  
Article
Transfer Learning-Based Ensemble of CNNs and Vision Transformers for Accurate Melanoma Diagnosis and Image Retrieval
by Murat Sarıateş and Erdal Özbay
Diagnostics 2025, 15(15), 1928; https://doi.org/10.3390/diagnostics15151928 - 31 Jul 2025
Viewed by 290
Abstract
Background/Objectives: Melanoma is an aggressive type of skin cancer that poses serious health risks if not detected in its early stages. Although early diagnosis enables effective treatment, delays can result in life-threatening consequences. Traditional diagnostic processes predominantly rely on the subjective expertise [...] Read more.
Background/Objectives: Melanoma is an aggressive type of skin cancer that poses serious health risks if not detected in its early stages. Although early diagnosis enables effective treatment, delays can result in life-threatening consequences. Traditional diagnostic processes predominantly rely on the subjective expertise of dermatologists, which can lead to variability and time inefficiencies. Consequently, there is an increasing demand for automated systems that can accurately classify melanoma lesions and retrieve visually similar cases to support clinical decision-making. Methods: This study proposes a transfer learning (TL)-based deep learning (DL) framework for the classification of melanoma images and the enhancement of content-based image retrieval (CBIR) systems. Pre-trained models including DenseNet121, InceptionV3, Vision Transformer (ViT), and Xception were employed to extract deep feature representations. These features were integrated using a weighted fusion strategy and classified through an Ensemble learning approach designed to capitalize on the complementary strengths of the individual models. The performance of the proposed system was evaluated using classification accuracy and mean Average Precision (mAP) metrics. Results: Experimental evaluations demonstrated that the proposed Ensemble model significantly outperformed each standalone model in both classification and retrieval tasks. The Ensemble approach achieved a classification accuracy of 95.25%. In the CBIR task, the system attained a mean Average Precision (mAP) score of 0.9538, indicating high retrieval effectiveness. The performance gains were attributed to the synergistic integration of features from diverse model architectures through the ensemble and fusion strategies. Conclusions: The findings underscore the effectiveness of TL-based DL models in automating melanoma image classification and enhancing CBIR systems. The integration of deep features from multiple pre-trained models using an Ensemble approach not only improved accuracy but also demonstrated robustness in feature generalization. This approach holds promise for integration into clinical workflows, offering improved diagnostic accuracy and efficiency in the early detection of melanoma. Full article
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18 pages, 432 KiB  
Article
Anthropometry and the Risk of Breast Cancer in Moroccan Women: A Large Multicentric Case-Control Study
by Najia Mane, Najoua Lamchabbek, Siham Mrah, Mohammed Saidi, Chaimaa Elattabi, Elodie Faure, Fatima Zahra El M’rabet, Adil Najdi, Nawfel Mellas, Karima Bendahou, Lahcen Belyamani, Boutayeb Saber, Karima El Rhazi, Chakib Nejjari, Inge Huybrechts and Mohamed Khalis
Curr. Oncol. 2025, 32(8), 434; https://doi.org/10.3390/curroncol32080434 - 31 Jul 2025
Viewed by 167
Abstract
Although evidence suggests adiposity as a modifiable risk factor for postmenopausal breast cancer (BC), its association with premenopausal BC remains uncertain. This potential differential relationship for menopausal status has been insufficiently investigated in the Moroccan population due to limited data. This study aims [...] Read more.
Although evidence suggests adiposity as a modifiable risk factor for postmenopausal breast cancer (BC), its association with premenopausal BC remains uncertain. This potential differential relationship for menopausal status has been insufficiently investigated in the Moroccan population due to limited data. This study aims to assess the relationship between various indicators of adiposity and the risk of BC among Moroccan women by menopausal status. A multicenter case-control study was conducted in Morocco between December 2019 and August 2023, including 1400 incident BC cases and 1400 matched controls. Detailed measures of adiposity and self-reported measures from different life stages were collected. Unconditional logistic regression analyses were conducted to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs) for the association between body size indicators and the risk of BC, adjusting for a range of known risk factors for BC. Higher waist circumference (WC) and hip circumference (HC) were associated with an increased risk of BC in both pre- (p-trend < 0.001 for both WC and HC) and post-menopausal women (p-trend < 0.001 for WC, 0.002 for HC). Current body mass index (BMI) ≥30 kg/m2 increased the risk of postmenopausal BC (p-trend = 0.012). Among postmenopausal women, higher weight at age 20 was positively associated with BC risk (p-trend < 0.001), while, weight at age 30 was significantly associated with increased BC risk in both pre- (p-trend = 0.008) and post-menopausal women (p-trend = 0.028). Interestingly, weight gain since age 20 was inversely associated with BC risk in postmenopausal women in the adjusted model (p-trend = 0.006). Young-adult BMI observed a significant increased trend with BC risk in both pre- (p-trend = 0.008) and post-menopausal women (p-trend < 0.001). In premenopausal women, larger body shape during childhood and early adulthood was positively associated with BC risk (p-trend = 0.01 and = 0.011, respectively). In postmenopausal women, larger childhood and adolescent body silhouettes were also associated with increased BC risk (p-trend = 0.045 and 0.047, respectively). These results suggest that anthropometric factors may have different associations with pre- and post-menopausal BC among Moroccan women. This underscores the importance of conducting large prospective studies to better understand these findings and explore their links to different molecular subtypes of BC. Full article
(This article belongs to the Section Breast Cancer)
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38 pages, 2158 KiB  
Review
Epigenetic Modulation and Bone Metastasis: Evolving Therapeutic Strategies
by Mahmoud Zhra, Jasmine Hanafy Holail and Khalid S. Mohammad
Pharmaceuticals 2025, 18(8), 1140; https://doi.org/10.3390/ph18081140 - 31 Jul 2025
Viewed by 496
Abstract
Bone metastasis remains a significant cause of morbidity and diminished quality of life in patients with advanced breast, prostate, and lung cancers. Emerging research highlights the pivotal role of reversible epigenetic alterations, including DNA methylation, histone modifications, chromatin remodeling complex dysregulation, and non-coding [...] Read more.
Bone metastasis remains a significant cause of morbidity and diminished quality of life in patients with advanced breast, prostate, and lung cancers. Emerging research highlights the pivotal role of reversible epigenetic alterations, including DNA methylation, histone modifications, chromatin remodeling complex dysregulation, and non-coding RNA networks, in orchestrating each phase of skeletal colonization. Site-specific promoter hypermethylation of tumor suppressor genes such as HIN-1 and RASSF1A, alongside global DNA hypomethylation that activates metastasis-associated genes, contributes to cancer cell plasticity and facilitates epithelial-to-mesenchymal transition (EMT). Key histone modifiers, including KLF5, EZH2, and the demethylases KDM4/6, regulate osteoclastogenic signaling pathways and the transition between metastatic dormancy and reactivation. Simultaneously, SWI/SNF chromatin remodelers such as BRG1 and BRM reconfigure enhancer–promoter interactions that promote bone tropism. Non-coding RNAs, including miRNAs, lncRNAs, and circRNAs (e.g., miR-34a, NORAD, circIKBKB), circulate via exosomes to modulate the RANKL/OPG axis, thereby conditioning the bone microenvironment and fostering the formation of a pre-metastatic niche. These mechanistic insights have accelerated the development of epigenetic therapies. DNA methyltransferase inhibitors (e.g., decitabine, guadecitabine) have shown promise in attenuating osteoclast differentiation, while histone deacetylase inhibitors display context-dependent effects on tumor progression and bone remodeling. Inhibitors targeting EZH2, BET proteins, and KDM1A are now advancing through early-phase clinical trials, often in combination with bisphosphonates or immune checkpoint inhibitors. Moreover, novel approaches such as CRISPR/dCas9-based epigenome editing and RNA-targeted therapies offer locus-specific reprogramming potential. Together, these advances position epigenetic modulation as a promising axis in precision oncology aimed at interrupting the pathological crosstalk between tumor cells and the bone microenvironment. This review synthesizes current mechanistic understanding, evaluates the therapeutic landscape, and outlines the translational challenges ahead in leveraging epigenetic science to prevent and treat bone metastases. Full article
(This article belongs to the Section Biopharmaceuticals)
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15 pages, 1843 KiB  
Article
Genotype-Specific HPV mRNA Triage Improves CIN2+ Detection Efficiency Compared to Cytology: A Population-Based Study of HPV DNA-Positive Women
by S. Sørbye, B. M. Falang, M. Antonsen and E. Mortensen
Pathogens 2025, 14(8), 749; https://doi.org/10.3390/pathogens14080749 - 30 Jul 2025
Viewed by 714
Abstract
Background: Effective triage of women testing positive for high-risk HPV DNA is essential to reduce unnecessary colposcopies while preserving cancer prevention. Cytology, the current standard, has limited specificity and reproducibility. The genotype-specific 7-type HPV E6/E7 mRNA test (PreTect HPV-Proofer’7), targeting HPV types 16, [...] Read more.
Background: Effective triage of women testing positive for high-risk HPV DNA is essential to reduce unnecessary colposcopies while preserving cancer prevention. Cytology, the current standard, has limited specificity and reproducibility. The genotype-specific 7-type HPV E6/E7 mRNA test (PreTect HPV-Proofer’7), targeting HPV types 16, 18, 31, 33, 45, 52, and 58, detects transcriptionally active infections and may enhance risk stratification. Methods: Between 2019 and 2023, 34,721 women aged 25–69 underwent primary HPV DNA screening with the Cobas 4800 assay at the University Hospital of North Norway, within the national screening program. Of these, 1896 HPV DNA-positive women were triaged with liquid-based cytology with atypical squamous cells of undetermined significance or worse (≥ASC-US) and the 7-type HPV mRNA test. Histological outcomes were followed through October 2024. Diagnostic performance for CIN2+ was evaluated overall and by genotype. Results: CIN2+ prevalence was 13.3%. The mRNA test reduced test positivity from 50.3% to 33.4% while maintaining comparable sensitivity (70.6% vs. 72.2%) and improving specificity (72.3% vs. 53.0%) and PPV (28.1% vs. 19.1%). Genotype-specific PPVs were highest for HPV16 mRNA (47.7%), followed by HPV33 (39.2%) and HPV31 (32.2%), all exceeding corresponding DNA-based estimates. Conclusion: Genotype-specific HPV mRNA triage offers superior risk discrimination compared to cytology, supporting more targeted, efficient, and accessible cervical cancer screening. Full article
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26 pages, 685 KiB  
Article
Novel Research Regarding Topical Use of Diclofenac in Dermatology—Non-Clinical and Clinical Data
by Diana Ana-Maria Nițescu, Horia Păunescu, Mihnea Costescu, Bogdan Nițescu, Laurențiu Coman, Ion Fulga and Oana Andreia Coman
Sci. Pharm. 2025, 93(3), 34; https://doi.org/10.3390/scipharm93030034 - 30 Jul 2025
Viewed by 261
Abstract
Diclofenac, an aryl-acetic acid derivative from the non-steroidal anti-inflammatory drug class, is the subject of multiple non-clinical and clinical studies regarding its usefulness in treating some dermatologic pathologies with an inflammatory, auto-immune, or proliferative component. Diclofenac is now approved for the topical treatment [...] Read more.
Diclofenac, an aryl-acetic acid derivative from the non-steroidal anti-inflammatory drug class, is the subject of multiple non-clinical and clinical studies regarding its usefulness in treating some dermatologic pathologies with an inflammatory, auto-immune, or proliferative component. Diclofenac is now approved for the topical treatment of actinic keratoses (AK), pre-malignant entities that have the risk of transformation into skin carcinomas. The hypothesis that diclofenac increases granular layer development in the mice tail model, having an anti-psoriatic effect, was demonstrated in a previous study in which 1% and 2% diclofenac ointment was evaluated. The aim of the present study was to perform experimental research on the topical effect of diclofenac in the mice tail model, by testing 4% and 8% diclofenac ointment, which is presented in the first part of the manuscript. In the second part of the manuscript, we also aimed to conduct a literature review regarding topical diclofenac uses in specific dermatological entities by evaluating the articles published in PubMed and Scopus databases during 2014–2025. The studies regarding the efficacy of topical diclofenac in dermatological diseases such as AK and field cancerization, actinic cheilitis, basal cell carcinoma, Bowen disease, Darier disease, seborrheic keratoses, and porokeratosis, were analyzed. The results of the experimental work showed a significant effect of 4% and 8% diclofenac ointment on orthokeratosis degree when compared to the negative control groups. Diclofenac in the concentration of 4% and 8% significantly increased the orthokeratosis degree compared to the negative control with untreated mice (p = 0.006 and p = 0.011, respectively, using the Kruskal–Wallis test) and to the negative control with vehicle (p = 0.006 and p = 0.011, respectively, using the Kruskal–Wallis test). The mean epidermal thickness was increased for the diclofenac groups, but not significantly when compared to the control groups. The results are concordant with our previous experiment, emphasizing the need for future clinical trials on the use of topical diclofenac in psoriasis. Full article
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