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12 pages, 553 KB  
Article
Distinct Systemic Inflammatory Signatures in Women with Endometriosis and Infertility Without Endometriosis: Implications for Assisted Reproduction
by Luana Ghilea (Seleș), Laura Maghiar, Viorela Romina Murvai, Goman Marius, Alin Bodog and Carmen Anca Huniadi
Medicina 2026, 62(9), 1641; https://doi.org/10.3390/medicina62091641 (registering DOI) - 27 Aug 2026
Abstract
Background and Objectives: Endometriosis is a chronic inflammatory disease associated with impaired fertility, but the extent to which its systemic inflammatory profile differs from that observed in infertile women without endometriosis remains incompletely understood. This study aimed to characterize and compare the systemic [...] Read more.
Background and Objectives: Endometriosis is a chronic inflammatory disease associated with impaired fertility, but the extent to which its systemic inflammatory profile differs from that observed in infertile women without endometriosis remains incompletely understood. This study aimed to characterize and compare the systemic inflammatory profiles of women with endometriosis, infertile women without endometriosis, and healthy controls by evaluating serum interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and high-sensitivity C-reactive protein (hs-CRP). In addition, the study explored the IL-6/TNF-α ratio as an indicator of inflammatory balance and evaluated its relationship with ovarian reserve. Materials and Methods: This observational comparative study included 87 women divided into three groups: healthy controls (n = 29), women with endometriosis (n = 29), and infertile women without endometriosis (n = 29). Serum IL-6, TNF-α, and hs-CRP concentrations were determined specifically for the present study, whereas the corresponding clinical and embryological data were retrieved from medical records. Group comparisons were performed using the Kruskal–Wallis test followed by Dunn’s post hoc test with Holm correction. The IL-6/TNF-α ratio was calculated as an exploratory indicator of inflammatory balance. Associations between inflammatory biomarkers and anti-Müllerian hormone (AMH) concentrations were assessed using Spearman’s correlation analysis. Results: Significant differences in serum inflammatory biomarkers were observed among the three groups. IL-6 concentrations were significantly increased in both women with endometriosis and infertile women without endometriosis compared with healthy controls, whereas TNF-α concentrations were significantly elevated only in infertile women without endometriosis compared with both healthy controls and women with endometriosis (adjusted p < 0.001 for both comparisons). Differences in hs-CRP were more modest but remained significant overall. Women with endometriosis exhibited a significantly higher IL-6/TNF-α ratio than infertile women without endometriosis, suggesting distinct inflammatory patterns between these conditions. No significant correlations were identified between circulating inflammatory biomarkers and AMH concentrations. Conclusions: Women with endometriosis and infertile women without endometriosis exhibit distinct systemic inflammatory profiles rather than simply different levels of inflammation. The IL-6/TNF-α ratio may provide additional information regarding the balance of inflammatory pathways beyond the isolated evaluation of individual cytokines. Larger prospective studies integrating systemic and local inflammatory biomarkers with assisted reproductive outcomes are warranted to validate these findings and further explore their clinical relevance. Full article
(This article belongs to the Special Issue Reproductive Medicine in Clinical Practice)
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19 pages, 13593 KB  
Article
Morpho-Functional Effects of Nonylphenol–Steroid Hormone Co-Exposure on Human Prostate PNT1A Cells
by Aldo Mileo, Teresa Chianese, Stefania Boccia, Francesca Carrella, Benedetta Sgangarella Valvano, Rosaria Sciarrillo, Luigi Rosati, Lucia Capasso, Antonio De Luca, Anna Capaldo and Maria De Falco
Toxics 2026, 14(9), 755; https://doi.org/10.3390/toxics14090755 - 26 Aug 2026
Abstract
Nonylphenol (NP) is a chemical compound belonging to the class of alkylphenols (APs), known for its widespread environmental distribution and endocrine-disrupting properties. It is commonly used in the production of detergents, pesticides, and plastic materials and, owing to these properties, it can accumulate [...] Read more.
Nonylphenol (NP) is a chemical compound belonging to the class of alkylphenols (APs), known for its widespread environmental distribution and endocrine-disrupting properties. It is commonly used in the production of detergents, pesticides, and plastic materials and, owing to these properties, it can accumulate in both aquatic and terrestrial ecosystems. As a xenoestrogenic compound, NP can bind steroid receptors, including estrogen receptors (ERs), thereby activating ER-dependent pathways. In this work, we investigated the effects of NP alone and in combination with the endogenous hormones 17β-oestradiol (E2) and/or testosterone (T) on a human non-tumoral prostate cell line (PNT1A). Cell viability and migration assays, together with analysis of ER expression and localization, were carried out to assess the xenoestrogenic activity of NP, particularly in the presence of E2 and T. Our results showed that NP retained its endocrine-disrupting features in the mixtures, positively affecting cell viability, except for the NP+E2 mixture, in which cell viability did not significantly differ from control, suggesting an antagonistic interaction between NP and E2. The mixtures also interfered with steroid receptor dynamics, affecting receptor expression and delaying receptor localization and activation kinetics. Moreover, all mixtures negatively affected cell migration compared with treatment with endogenous hormones alone. In conclusion, our results demonstrate that NP retains its xenoestrogenic behavior in mixture, inducing a significant alteration in prostate cell homeostasis. Full article
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24 pages, 8658 KB  
Article
Post-VABB Cavity-Targeted Avidin-Pretargeted [90Y]Y-DOTA-Biotin in Nonpalpable Breast Cancer: A Phase I Activity-Escalation Study (ARTHE)
by Maddalena Sansovini, Paola Sanna, Paola Possanzini, Emanuela Scarpi, Irene Marini, Silvia Nicolini, Ilaria Grassi, Paola Caroli, Michele Amadori, Annalisa Curcio, Giulia Simoncini, Lucia Fabbri, Oriana Nanni, Manuela Monti, Lilla Vizza, Anna Miserocchi, Valentina Di Iorio, Cristina Cuni, Maria Luisa Belli, Matteo Costantini, Fabio Falcini, Giovanni Paganelli, Federica Matteucci and Anna Sarnelliadd Show full author list remove Hide full author list
Cancers 2026, 18(17), 2760; https://doi.org/10.3390/cancers18172760 - 25 Aug 2026
Abstract
Background/Objectives: Vacuum-assisted breast biopsy (VABB) is widely used for the diagnosis of nonpalpable breast cancer but is not considered definitive treatment because microscopic residual disease may persist within or around the biopsy cavity. The ARTHE phase I trial evaluated a cavity-targeted radionuclide strategy [...] Read more.
Background/Objectives: Vacuum-assisted breast biopsy (VABB) is widely used for the diagnosis of nonpalpable breast cancer but is not considered definitive treatment because microscopic residual disease may persist within or around the biopsy cavity. The ARTHE phase I trial evaluated a cavity-targeted radionuclide strategy based on same-session sequential intralesional administration of avidin followed by [90Y]Y-DOTA-biotin after VABB. Methods: Eighteen women with nonpalpable breast cancer measuring ≤15 mm and a skin-to-cavity distance ≥ 13 mm were treated in three sequential activity-escalation cohorts. The primary objective was to assess acute local and systemic safety, including dose-limiting toxicity. The protocol-specified co-primary objective was to evaluate preliminary antitumor activity, assessed as breast-only pathologic complete response (pCR) at surgery. Given the phase I single-arm design, pCR was analyzed descriptively. The protocol-specified secondary objective was patient-specific dosimetry. Additional exploratory assessments included post-injection biodistribution and integration with subsequent breast-conserving surgery. Results: No dose-limiting toxicities, grade ≥ 3 adverse events, clinically relevant hematologic toxicity, treatment discontinuations, hospitalizations, or treatment-related surgical delays were observed. Local toxicity was limited to grade 1 injection-site pain and/or erythema. Post-injection imaging consistently demonstrated focal intralesional localization without clinically relevant extra-lesional uptake. All patients underwent breast-conserving surgery 4–7 weeks after treatment. No residual tumor cellularity (RTC), from either invasive or in situ carcinoma, was identified in the breast surgical specimen in 5/18 patients (27.8%). However, because diagnostic VABB may have removed part or all of the malignant lesion, the absence of residual carcinoma at surgery cannot be attributed specifically to the radionuclide treatment. Conclusions: The intralesional avidin-mediated local trapping strategy using [90Y]Y-DOTA-biotin after VABB was feasible, showed favorable acute and short-term tolerability, was associated with early focal localization on post-injection imaging, and was compatible with standard breast-conserving surgery. Controlled studies are warranted to determine the therapeutic contribution of this post-biopsy cavity-targeted strategy, optimize administered activity, and refine patient selection. Full article
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12 pages, 1113 KB  
Article
Feasibility of Conventional Abdominal Ultrasound for Monitoring Tumor Size After Stereotactic Body Radiotherapy for Hepatocellular Carcinoma
by Masayuki Ueno, Yohei Yamanouchi, Hideki Hanazawa, Hiroyuki Takabatake, Takahisa Kayahara, Youichi Morimoto, Satoshi Itasaka, Hirokazu Mouri and Motowo Mizuno
Biomedicines 2026, 14(9), 1893; https://doi.org/10.3390/biomedicines14091893 - 25 Aug 2026
Abstract
Background/Objectives: Stereotactic body radiotherapy (SBRT) is increasingly used for hepatocellular carcinoma (HCC) that is unsuitable for surgery, radiofrequency ablation (RFA), or transplantation. Although current evidence for imaging assessment after SBRT is largely based on contrast-enhanced computed tomography (CT) or magnetic resonance imaging [...] Read more.
Background/Objectives: Stereotactic body radiotherapy (SBRT) is increasingly used for hepatocellular carcinoma (HCC) that is unsuitable for surgery, radiofrequency ablation (RFA), or transplantation. Although current evidence for imaging assessment after SBRT is largely based on contrast-enhanced computed tomography (CT) or magnetic resonance imaging (MRI), repeated contrast-enhanced imaging may be difficult to perform at every routine follow-up visit. Thus, we evaluated whether conventional abdominal ultrasound (US) can monitor tumor size after SBRT for HCC. Methods: We retrospectively reviewed 67 consecutive patients who underwent SBRT for HCC at our institution between January 2015 and October 2020. After excluding patients treated for local recurrence after RFA or transarterial chemoembolization, those whose lesions were not visible on pretreatment US, and those without follow-up US within one year, 32 patients with 32 nodules were analyzed. Tumor visibility and size changes on US were assessed before treatment and at <6, 6–12, and 12–18 months after SBRT. Results: The treated lesion was identified as a discrete nodule on US in 100% (15/15; 95% CI, 78.2–100%), 75.0% (18/24; 95% CI, 53.3–90.2%), and 50.0% (8/16; 95% CI, 24.7–75.3%) of examinations at <6, 6–12, and 12–18 months, respectively. In all cases in which the lesion was no longer measurable on US, contrast-enhanced CT/MRI showed complete or partial response. Local tumor progression occurred in one patient (3.1%) during a median follow-up of 24.1 months; in this patient, interval enlargement was first detected by US 3.7 months after SBRT and was subsequently confirmed by dynamic CT/MRI. Conclusions: These descriptive findings suggest that in selected patients with lesions clearly visible on pretreatment US, conventional abdominal US may provide complementary morphologic information during the first year after SBRT when used alongside periodic dynamic CT/MRI. Prospective validation is required before routine implementation. Full article
(This article belongs to the Special Issue Hepatocellular Carcinoma: Diagnosis, Pathophysiology, and Treatment)
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22 pages, 2073 KB  
Article
Clinical Characteristics, Treatment Patterns, and Survival Outcomes of Right-Sided RAS/RAF Wild-Type Metastatic Colorectal Cancer: A Real-World Multicenter Cohort Study
by Nur Deniz Yildiz, Çağatay Arslan, İlker Nihat Okten, Umut Kefeli, Mahmut Emre Yildirim, Nuri Karadurmus, Tuba Baydas, Bülent Karabulut, Irfan Cicin, Cemil Bilir, Melike Ozcelik, Timucin Cil, Sinemis Celik, Oktay Bozkurt, Hakan Harputluoglu, Bala Başak Oven, Mehmet Artaç, Hacı Mehmet Türk, Ahmet Alacacıoğlu, Mahmut Gumus and Şuayib Yalcinadd Show full author list remove Hide full author list
Clin. Pract. 2026, 16(9), 158; https://doi.org/10.3390/clinpract16090158 - 24 Aug 2026
Viewed by 107
Abstract
Background: Right-sided metastatic colon cancer represents a clinically distinct subgroup with inferior outcomes and uncertain optimal biologic treatment selection, even among patients with RAS wild-type disease. Real-world data focusing specifically on right-sided RAS wild-type metastatic colon cancer remain limited. This study aimed [...] Read more.
Background: Right-sided metastatic colon cancer represents a clinically distinct subgroup with inferior outcomes and uncertain optimal biologic treatment selection, even among patients with RAS wild-type disease. Real-world data focusing specifically on right-sided RAS wild-type metastatic colon cancer remain limited. This study aimed to describe clinicopathologic characteristics, metastatic patterns, treatment approaches, and survival outcomes in this population using a national multicenter registry. Methods: This retrospective multicenter cohort study was conducted using data from the ONKO-KOLON Türkiye registry. Patients with pathologically confirmed KRAS/NRAS wild-type metastatic colorectal cancer and available primary tumor localization were evaluated. The main analytic cohort included patients with right-sided metastatic colon cancer, defined as right colon or transverse colon tumors. Left-sided colon cancer patients were used as a contextual comparator, while rectal cancer patients were excluded from sidedness-based colon comparisons. Survival outcomes were estimated using the Kaplan–Meier method, and prognostic factors were evaluated using Cox regression analyses. Results: Among 1079 patients in the source cohort, primary tumor localization was available in 1065 patients. Of these, 213 had right-sided colon cancer, 464 had left-sided colon cancer, and 388 had rectal cancer. In the right-sided cohort, median age was 61.5 years, 64.3% were male, and 66.7% had synchronous/de novo metastatic disease. Liver metastasis was the most common metastatic site (63.4%), followed by lymph node (31.0%), lung (21.1%), and peritoneal metastases (15.5%). First-line anti-VEGF-based treatment was used in 46.0% of patients, while anti-EGFR-based treatment was used in 40.8%. Among evaluable patients, the objective response rate was 46.8% and the disease control rate was 79.2%. Median progression-free survival was 10.0 months, and median overall survival was 24.0 months. In unadjusted exploratory analysis, median OS was 27.0 months with anti-EGFR-based treatment and 17.0 months with anti-VEGF-based treatment (log-rank p = 0.022), whereas median PFS was 10.0 months in both groups. In an extended covariate-adjusted multiple-imputation sensitivity model, the anti-EGFR OS estimate did not meet statistical significance (adjusted HR 0.66, 95% CI 0.43–1.00; p = 0.051). In a secondary contextual comparison, median overall survival was shorter in the right-sided than in the left-sided colon cancer group (24.0 vs. 28.0 months; HR 1.47, 95% CI 1.19–1.82; p < 0.001), whereas progression-free survival did not differ significantly. Conclusions: This study provides a descriptive account of metastatic patterns, treatment approaches, and outcomes in a dedicated right-sided RAS wild-type metastatic colon cancer cohort. The unadjusted OS difference between biological treatment groups was not confirmed after measured covariate adjustment and should not be interpreted as evidence of comparative treatment effectiveness. Because molecular profiling was incomplete, this study cannot identify biomarker-defined treatment subgroups. Prospective studies with complete, predefined molecular characterization are needed before molecularly informed treatment selection hypotheses can be evaluated in this population. Full article
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52 pages, 7768 KB  
Review
Smart Mesoporous Silica Nanoparticle-Based Drug Delivery Systems: Recent Advances in Biomedical Applications, Wound Healing and Therapeutic Perspectives
by Manickam Rajkumar, Nadarajan Prathap, Vivekanand Ankush Kashid, Bhupendra G. Prajapati, Kokila Palani, Parappurath Narayanan Sudha, Prabhakaran Rajkumar and Biswajit Basu
Pharmaceutics 2026, 18(8), 1044; https://doi.org/10.3390/pharmaceutics18081044 - 21 Aug 2026
Viewed by 378
Abstract
Mesoporous silica nanoparticles (MSNs) have emerged as versatile nanocarriers for biomedical applications because of their unique physicochemical properties, including high surface area, large pore volume, excellent drug-loading capacity, controllable biodegradation, and facile surface functionalization. These characteristics have enabled the development of advanced drug [...] Read more.
Mesoporous silica nanoparticles (MSNs) have emerged as versatile nanocarriers for biomedical applications because of their unique physicochemical properties, including high surface area, large pore volume, excellent drug-loading capacity, controllable biodegradation, and facile surface functionalization. These characteristics have enabled the development of advanced drug delivery systems with enhanced therapeutic efficacy, targeted delivery, improved bioavailability, and reduced systemic toxicity. Recent advances in MSN synthesis, physicochemical properties, surface engineering, and functionalization strategies have significantly improved their biological performance and therapeutic potential. In particular, integrating polymers, lipids, and liposomes with MSN platforms has enhanced colloidal stability, circulation time, cellular uptake, and target specificity, thereby facilitating efficient, stimuli-responsive drug delivery. This review highlights MSN-based drug delivery systems in cancer therapy, where multifunctional nanocarriers enable site-specific delivery, controlled drug release, enhanced tumor accumulation, and reduced off-target effects. The review discusses the expanding roles of MSNs in antimicrobial therapy, wound healing, tissue engineering, and regenerative medicine, emphasizing their ability to promote localized therapeutic delivery, immunomodulation, angiogenesis, and tissue regeneration. The review discusses the diagnostic and theragnostic capabilities of MSNs for disease imaging and monitoring. It also critically evaluates current challenges related to biocompatibility, biodegradation, toxicity, biological barriers, large-scale manufacturing, clinical translation, and regulatory considerations. This review provides a comprehensive overview of recent progress, current limitations, and future opportunities for MSN-based platforms in targeted drug delivery and advanced biomedical applications, supporting their continued advancement toward clinical translation and precision medicine. Full article
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22 pages, 4640 KB  
Review
Breast-Conserving Surgery in Multicentric Breast Cancer: Evolving Evidence and Patient Selection
by Mariam Rizk and Kefah Mokbel
Cancers 2026, 18(16), 2705; https://doi.org/10.3390/cancers18162705 - 21 Aug 2026
Viewed by 259
Abstract
Multicentric breast cancer—two or more biopsy-proven tumor foci in anatomically distinct regions of the same breast—has historically been treated as a near-automatic indication for mastectomy, reflecting concerns about occult residual disease, achievability of negative margins at every focus, and unacceptable cosmetic outcome. This [...] Read more.
Multicentric breast cancer—two or more biopsy-proven tumor foci in anatomically distinct regions of the same breast—has historically been treated as a near-automatic indication for mastectomy, reflecting concerns about occult residual disease, achievability of negative margins at every focus, and unacceptable cosmetic outcome. This narrative review synthesizes the evidence underlying that historical position and the more recent data that have begun to qualify it. The single-arm ACOSOG Z11102 (Alliance) trial reported a 5-year local recurrence rate of 3.1% after breast-conserving therapy for two to three ipsilateral foci and recent retrospective cohorts report comparable to local control. These findings sit alongside a persistent and unresolved tension around preoperative MRI, which improves detection of additional foci but has not demonstrated improvement in local control or survival outcomes in randomized trials, despite increasing mastectomy conversion. We review the definitions and biology of multifocal and multicentric disease, the maturing role of oncoplastic technique, margin and radiotherapy planning considerations specific to multicentric resection, the evolving use of neoadjuvant systemic therapy, hereditary cancer considerations, and the current guideline landscape (ASBrS, NCCN, ESMO, AGO). We propose a practical, multidisciplinary framework for patient selection and identify the principal gaps—absence of randomized comparison with mastectomy, unresolved necessity of routine MRI, and limited data on breast conservation after neoadjuvant therapy specifically in multicentric disease—that should guide both clinical decision-making and future research. Full article
(This article belongs to the Special Issue Current Advances in Surgical and Systemic Treatment of Breast Cancer)
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46 pages, 19374 KB  
Review
The Invasive Margin of Glioblastoma as a Molecular Ecosystem: Spatial Heterogeneity, Tumor–Host Interactions, and Therapeutic Opportunities
by Nikodem Kuczyński, Dawid Larysz, Dorota Uchman-Rzeżnik, Gunawan Irianto and Dawid Pilewski
Int. J. Mol. Sci. 2026, 27(16), 7449; https://doi.org/10.3390/ijms27167449 - 20 Aug 2026
Viewed by 169
Abstract
Glioblastoma (GBM) recurs predominantly from infiltrative disease that persists beyond the contrast-enhancing tumor (CET). This structured narrative review aims to define the invasive margin and peritumoral brain zone (PBZ) as a spatially organized molecular ecosystem, summarize the approaches used to interrogate this compartment, [...] Read more.
Glioblastoma (GBM) recurs predominantly from infiltrative disease that persists beyond the contrast-enhancing tumor (CET). This structured narrative review aims to define the invasive margin and peritumoral brain zone (PBZ) as a spatially organized molecular ecosystem, summarize the approaches used to interrogate this compartment, and evaluate how malignant-cell plasticity, host niches, and treatment-induced remodeling contribute to minimal residual disease and recurrence. A structured literature search of PubMed/MEDLINE, Scopus, and Web of Science identified the clinical, translational, preclinical, and review literature available through July 2026; evidence was synthesized qualitatively, with priority given to human tissue studies and single-cell or spatially resolved analyses. Across studies, the margin differs from both tumor core and normal brain and contains heterogeneous malignant states interacting with neural, vascular, immune, hypoxic, and extracellular-matrix-supported niches. Surgery, radiotherapy, and systemic treatment further reshape these interactions through inflammation, vascular injury, senescence, hypoxia, and fibrosis. The main translational challenge is therefore not simply to control the CET, but to identify biologically high-risk non-enhancing tissue and demonstrate that therapy reaches and modifies it. We propose three priorities: image-registered characterization of residual compartments, regional measurement of drug exposure and target engagement, and integration of local margin control with distributed and niche-directed treatment. Prospective validation is required before spatial PBZ biomarkers can guide routine care. Full article
(This article belongs to the Special Issue Molecular Insights into Glioblastoma Pathogenesis and Therapeutics)
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22 pages, 1614 KB  
Review
A Pathway to Chordoma Treatment: A Review on CDKN2A and Therapeutic Targeting
by Muneeb Mohiuddin, Benjamin Vaca, Elijah Haynal, Othman Bin-Alamer, Peter Zaki, Hussam Abou-Al-Shaar, Georgios A. Zenonos, Hector A. Perez, Miguel Lopez-Gonzalez and Zachary C. Gersey
Cancers 2026, 18(16), 2688; https://doi.org/10.3390/cancers18162688 - 19 Aug 2026
Viewed by 237
Abstract
Background: Chordoma is a rare malignant bone tumor thought to arise from remnants of the embryonic notochord. Its management remains challenging because of its proximity to critical neurovascular structures and its high propensity for local recurrence. Current standard treatment consists of maximal safe [...] Read more.
Background: Chordoma is a rare malignant bone tumor thought to arise from remnants of the embryonic notochord. Its management remains challenging because of its proximity to critical neurovascular structures and its high propensity for local recurrence. Current standard treatment consists of maximal safe resection followed by radiotherapy, yet durable disease control remains difficult to achieve in many patients. Emerging evidence suggests that cyclin-dependent kinase inhibitor 2A (CDKN2A) loss is a recurrent molecular event in chordoma and may serve as both a prognostic biomarker and a therapeutic target. Methods: A literature search was performed by acquiring articles containing “(CDKN2A or p16) AND (chordoma or notochordal tumor)”, and “chordoma 9p21”. Of the 41 articles retrieved, 17 met the inclusion criteria. Results: Homozygous and heterozygous CDKN2A deletions were frequently identified in chordoma using fluorescence in situ hybridization and genomic sequencing approaches. These alterations were commonly associated with loss of p16^INK4A expression, the protein product of CDKN2A, supporting a role in tumorigenesis and disease progression. Epigenetic mechanisms may also contribute to reduced p16^INK4A expression in a subset of tumors. Preclinical studies in CDKN2A-deficient chordoma cell lines and patient-derived xenografts demonstrated sensitivity to cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors, including palbociclib, flavopiridol, and abemaciclib. Combination strategies pairing palbociclib with buparlisib or rapamycin produced greater antitumor effects, particularly in p16^INK4A- and PTEN-deficient models. In addition, CDKN2A loss has been associated with adverse clinical features in selected cohorts, although its independent prognostic significance remains unclear. Available preclinical evidence further suggests that chordomas lacking p16^INK4A expression and retaining retinoblastoma pathway dependence may be particularly susceptible to CDK4/6 inhibition. Conclusions: CDKN2A loss is a recurrent molecular alteration in chordoma that is associated with reduced p16^INK4A expression, adverse clinicopathologic features, and less favorable outcomes in selected cohorts, although its independent prognostic significance remains inconsistent. Preclinical data support CDK4/6 inhibition, particularly in biomarker-selected CDKN2A-deficient tumors, and suggest that combination approaches targeting complementary pathways such as PI3K/mTOR may further enhance therapeutic efficacy. Together, these findings support the clinical relevance of CDKN2A as both a prognostic biomarker and a promising therapeutic target in chordoma. Full article
(This article belongs to the Section Cancer Therapy)
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25 pages, 2610 KB  
Article
High-Throughput Discovery of Near-Infrared Oxazine Probes for Fluorescence-Guided Glioblastoma Surgery
by Vince Cataldi, Dhanir Tailor, Antonio R. Montano, Syed Zaki Husain Rizvi, Samrat Chakraborty, Joshua C. Saldivar, Sanjay V. Malhotra, Lei G. Wang, Summer L. Gibbs and Adam W. G. Alani
Cancers 2026, 18(16), 2684; https://doi.org/10.3390/cancers18162684 - 19 Aug 2026
Viewed by 263
Abstract
Background/Objectives: Glioblastoma (GBM) is the most aggressive primary malignant brain tumor in adults, characterized by highly infiltrative growth and poorly defined margins that hinder complete surgical resection. Fluorescence-guided surgery (FGS) can enhance intraoperative tumor visualization; however, currently available fluorophores often exhibit limited tumor [...] Read more.
Background/Objectives: Glioblastoma (GBM) is the most aggressive primary malignant brain tumor in adults, characterized by highly infiltrative growth and poorly defined margins that hinder complete surgical resection. Fluorescence-guided surgery (FGS) can enhance intraoperative tumor visualization; however, currently available fluorophores often exhibit limited tumor specificity and inconsistent labeling. This study aimed to identify near-infrared (NIR) probes with improved glioblastoma selectivity using a high-throughput discovery approach. Methods: A chemically diverse library of 127 NIR oxazine probes was screened using automated fluorescence imaging across four GBM cell lines and a sarcoma control line. Top-performing probes were further evaluated in an orthotopic U251MG-GFP glioblastoma mouse model to assess blood–brain barrier penetration and tumor localization in vivo. Results: Five candidate probes exhibited strong, selective NIR fluorescence in GBM cells. In vivo imaging revealed that the lead probe, LGW01-44, achieved the highest tumor-to-brain contrast with minimal background signal. Ex vivo analysis of brain sections confirmed preferential accumulation of LGW01-44 within intracranial tumor tissue. Conclusions: These findings establish a scalable high-throughput platform for the discovery of tumor-selective NIR imaging agents and identify the oxazine probe LGW01-44 as a promising candidate for fluorescence-guided glioblastoma surgery. Full article
(This article belongs to the Section Cancer Therapy)
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41 pages, 5924 KB  
Review
25 Years of Cancer Immunoediting: Dendritic Cells and Macrophages Filled the Missing Gap
by Vijay Kumar and John H. Stewart IV
Cancers 2026, 18(16), 2672; https://doi.org/10.3390/cancers18162672 - 18 Aug 2026
Viewed by 397
Abstract
In 1909, Paul Ehrlich first suggested that the immune system is critical for suppressing carcinogenesis and cancer growth, which led to the introduction of cancer immunosurveillance by Sir MacFarlane Burnet in 1960. Burnet’s cancer immunosurveillance was further supported and elaborated by Thomas Lewis [...] Read more.
In 1909, Paul Ehrlich first suggested that the immune system is critical for suppressing carcinogenesis and cancer growth, which led to the introduction of cancer immunosurveillance by Sir MacFarlane Burnet in 1960. Burnet’s cancer immunosurveillance was further supported and elaborated by Thomas Lewis in 1982, who noted, for example, the limitations of investigating cancer immunosurveillance in available experimental models, except for virus-induced cancers. The concept of cancer immunosurveillance in 2001 was revised to cancer immunoediting (the immunoediting term was introduced by Dr. Rober Schreiber), based on findings that the immune system not only controls tumorigenesis and tumor growth but also tumor quality/grade or immunogenicity. Advances in immunology, including the identification of target organs and the local immune system, and the identification of novel innate immune cells regulating the adaptive immune response, have further advanced the understanding of cancer immunosurveillance and immunoediting. The current article discusses the evolution of the cancer immunosurveillance hypothesis into cancer immunoediting. At the time of the introduction of cancer immunoediting, the direct role of dendritic cells (DCs) in tumor immunity and immunoediting was not much explored. Similarly, the concept of tumor-associated macrophages (TAMs) and their role in cancer immunosurveillance and immunoediting was not much studied. The current article discusses the evolution of DCs and TAMs in the context of tumor immunity, cancer immunoediting, and immunotherapies specifically targeting these innate immune cells. Full article
(This article belongs to the Special Issue Immunoediting in Cancer Therapies)
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15 pages, 860 KB  
Review
Surgical Management of Recurrent Brain Metastases: A Review
by James W. Sampson, Eric A. Goethe and Sherise D. Ferguson
Cancers 2026, 18(16), 2671; https://doi.org/10.3390/cancers18162671 - 18 Aug 2026
Viewed by 284
Abstract
As survival for cancer patients improves, the incidence of brain metastases has risen. This is likely due to improved systemic disease control, increased diligence in surveillance imaging in high-risk pathologies, improved neuro-imaging techniques and increased systemic screening for clinical trial enrollment. While there [...] Read more.
As survival for cancer patients improves, the incidence of brain metastases has risen. This is likely due to improved systemic disease control, increased diligence in surveillance imaging in high-risk pathologies, improved neuro-imaging techniques and increased systemic screening for clinical trial enrollment. While there are well-established treatments for brain metastases, many patients will experience recurrence after definitive treatment. The management of these recurrent lesions is not well established and often varies on a per-patient basis, owing to the clinical complexity and variety of these patients. Patients with recurrent brain metastases have surgical procedural options to achieve local tumor control, including laser interstitial thermal therapy (LITT) repeat open surgical resection with or without placement of intracavity brachytherapy. Repeat resection can offer rapid improvement in neurological symptoms, performance status, and potentially survival. LITT is less invasive than a standard craniotomy but offers a chance at directed local treatment while still obtaining tissue for diagnostic purposes and achieving acceptable survival outcomes. Further study is needed to determine the role of LITT for recurrent brain metastases, but it is a useful tool, particularly for patients with deep-seated lesions who may not tolerate a large surgery. Intracavitary brachytherapy allows for the immediate delivery of highly conformal radiation to the surgical bed with excellent local control and low rates of radiation necrosis, even in previously irradiated patients. The decision regarding which of the above to employ for recurrent brain metastases will vary on a case-by-case basis, and further studies are needed to standardize their use for this growing problem. Full article
(This article belongs to the Special Issue Advances in the Management and Prognosis of Brain Metastases)
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13 pages, 5046 KB  
Article
An Outer Membrane Vesicle-Based Vaccine Combined with alb-Flt3L Promotes Durable Antitumor Immunity in HPV-Associated Cancer
by Yining Liu, Yichu Xu, Yu-Cheng Chang, Ya-Chea Tsai, Tzyy-Choou Wu and Chien-Fu Hung
Vaccines 2026, 14(8), 707; https://doi.org/10.3390/vaccines14080707 - 18 Aug 2026
Viewed by 242
Abstract
Background/Objectives: Human papillomavirus (HPV)-associated cancers remain a major global health burden, and no therapeutic cancer vaccine has yet been approved. Oncoprotein E7 plays a key role in tumor initiation and progression and has been identified as a potential target. Here, we aim [...] Read more.
Background/Objectives: Human papillomavirus (HPV)-associated cancers remain a major global health burden, and no therapeutic cancer vaccine has yet been approved. Oncoprotein E7 plays a key role in tumor initiation and progression and has been identified as a potential target. Here, we aim to improve the efficacy and durability of an outer membrane vesicle (OMV)-based E7-targeted vaccine, SOMV-9RE7, through alb-Flt3L combination therapy. Methods: The antitumor efficacy and durability of the combination therapy were evaluated in low-burden and high-burden HPV-positive TC-1 tumor-bearing mouse models. Systemic and local immune responses were investigated by flow cytometry. Results: Combination with alb-Flt3L improved the tumor control and prolonged the therapeutic durability of SOMV-9RE7 compared with monotherapy groups, with more than half of the treated mice surviving beyond 60 days. This combination strategy enhanced E7-specific CD8+ T cell immunity in peripheral blood and the spleen, reduced myeloid-derived suppressor cell (MDSC)-mediated immunosuppression, promoted splenic T cell memory formation, and reshaped the tumor microenvironment. Conclusions: Combining vaccine SOMV-9RE7 with alb-Flt3L improves antitumor efficacy and durability. This therapeutic benefit is associated with both systemic and local immune remodeling, supporting the combination therapy as a promising strategy for therapeutic cancer vaccines. Full article
(This article belongs to the Section Human Papillomavirus Vaccines)
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17 pages, 32864 KB  
Case Report
Resolution of Recurrent Severe Hypoglycemia After Surgical Excision of a Primary Hepatic Neoplasm of Uncertain Histogenesis in a Dog: A Case Report
by Hyeong-Wook Moon, Chi-Youn Song, Jong-Myung Lee, Kwang-Rae Jo, Geun-Bo Park, Hye-Soo Shim, Hwi-Yool Kim and Jung-Moon Kim
Vet. Sci. 2026, 13(8), 822; https://doi.org/10.3390/vetsci13080822 - 18 Aug 2026
Viewed by 278
Abstract
Primary hepatic neoplasms in dogs, while uncommon, are occasionally associated with severe hypoglycemia, although the underlying mechanism may be difficult to establish. A 7-year-old castrated male Maltese dog weighing 3.6 kg was referred for recurrent bilateral pelvic limb weakness, episodic collapse, and abdominal [...] Read more.
Primary hepatic neoplasms in dogs, while uncommon, are occasionally associated with severe hypoglycemia, although the underlying mechanism may be difficult to establish. A 7-year-old castrated male Maltese dog weighing 3.6 kg was referred for recurrent bilateral pelvic limb weakness, episodic collapse, and abdominal distension. Severe hypoglycemia was documented, with a blood glucose concentration of 26 mg/dL. Computed tomography revealed a large mass arising from the right lateral liver lobe, with no identifiable pancreatic mass or distant metastasis. The serum insulin concentration measured during hypoglycemia was low at 1.0 μU/mL, making insulinoma less likely. Glycemic control temporarily or partially improved during prednisolone treatment; however, severe hypoglycemia recurred after prednisolone discontinuation before surgery. The hepatic mass was surgically excised. Dextrose-containing intravenous fluids were maintained for 6 h postoperatively, and no recurrent clinically significant hypoglycemia was documented after their discontinuation. Histopathologic examination revealed a poorly differentiated neoplasm with mesenchymal morphology, occasional cytoplasmic vacuolation, and no unequivocal lipoblasts. The neoplastic cells showed diffuse vimentin immunoreactivity, weak cytoplasmic S-100 immunoreactivity in a subset of cells, and no immunoreactivity for smooth-muscle actin or hepatocyte paraffin 1. These findings raised the possibility of adipocytic differentiation but were insufficient to establish a specific tumor lineage; therefore, the lesion was classified as a primary hepatic neoplasm of uncertain histogenesis. At 247 days after surgery, the dog remained normoglycemic without supplemental glucose or glucocorticoid treatment, and no imaging evidence of local recurrence or distant metastasis was identified. The postoperative course supported an association between the hepatic neoplasm and hypoinsulinemic hypoglycemia. Non-islet-cell tumor hypoglycemia was suspected but remained unconfirmed because an insulin-like growth factor-mediated mechanism was not demonstrated. Full article
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26 pages, 7639 KB  
Article
Magnetic Hyperthermia via Zn0.2Mn0.8Fe2O4 Oleic Acid Nanoparticles Enhances Chemotherapy Efficacy in a Lewis Lung Carcinoma Model
by Denis E. Yakobson, Mikhail N. Zharkov, Oleg A. Kulikov, Vasilisa I. Kulikova, Vladislav S. Bobrov, Aleksey O. Makarov, Ekaterina P. Brodovskaya, Larisa A. Balykova, Ran Yan and Nikolay A. Pyataev
Pharmaceutics 2026, 18(8), 1021; https://doi.org/10.3390/pharmaceutics18081021 - 17 Aug 2026
Viewed by 307
Abstract
Background/Objectives: Combining chemotherapy with local magnetic hyperthermia (MHT) is promising because heating tumor tissue can increase cell damage, sensitize cells to cytostatic drugs, impair DNA repair, and change tumor microenvironment permeability. This creates conditions for enhancing the antitumor efficacy of chemotherapy while [...] Read more.
Background/Objectives: Combining chemotherapy with local magnetic hyperthermia (MHT) is promising because heating tumor tissue can increase cell damage, sensitize cells to cytostatic drugs, impair DNA repair, and change tumor microenvironment permeability. This creates conditions for enhancing the antitumor efficacy of chemotherapy while potentially reducing systemic toxicity. The aim of this study was to evaluate the efficacy of MHT with Zn0.2Mn0.8Fe2O4@OA nanoparticles alone and in combination with cisplatin in a Lewis lung carcinoma model. Methods: Four types of magnetic nanoparticles were synthesized and characterized: Fe3O4 and Zn0.2Mn0.8Fe2O4 coated with oleic acid (OA) or SiO2-NH2. Their physicochemical and magnetothermal properties, cytotoxicity, reactive oxygen species generation, and biodegradation in vivo were evaluated. Antitumor efficacy was studied in C57Bl/6 mice with LLC tumors after intratumoral administration of nanoparticles and two MHT sessions (100 kHz, 8 kA/m, 30 min). In combination therapy, ZnMn@OA and cisplatin at doses of 9 or 18 mg/kg were used. Results/Conclusions: Zn0.2Mn0.8Fe2O4@OA combined efficient heating, biodegradation, and the most pronounced effect among the MHT-alone groups, although MHT without chemotherapy did not provide sustained inhibition of tumor growth or a significant increase in survival. The combination of Zn0.2Mn0.8Fe2O4@OA-MHT with cisplatin 9 mg/kg produced the best therapeutic outcome: median survival increased significantly by two fold compared with the control group and by 1.8-fold compared with the chemotherapy-alone group at the comparable cisplatin dose. This regimen also stabilized body weight, reduced systemic toxicity, and restored RBC, HGB, and HCT parameters to the level of healthy animals by day 7 of the experiment. These data confirm the potential of MHT as a chemosensitizing approach that improves the efficacy and tolerability of cisplatin therapy. Full article
(This article belongs to the Special Issue Functionalized Metal Nanoparticles in Cancer Therapy)
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