Search Results (807)

Radiation-induced keratoconjunctivitis sicca (KCS) is a significant late complication in dogs receiving radiation therapy for intranasal tumors, particularly with hypofractionated intensity-modulated radiation therapy (IMRT). This retrospective case-control study was performed to identify anatomical and dosimetric risk factors for KCS in 15 canine patients treated with IMRT delivered in 4–6 weekly fractions of 8 Gy. Orbital structures were retrospectively contoured, and dose–volume metrics (D50) were calculated. Receiver operating characteristic (ROC) curve analysis and odds ratios were used to evaluate the associations between radiation dose and KCS development. Six dogs (33%) developed KCS within three months post-treatment. Statistically significant dose differences were observed between affected and unaffected eyes for the eyeball, cornea, and retina. ROC analyses identified dose thresholds predictive of KCS: 13.8 Gy (eyeball), 14.9 Gy (cornea), and 17.0 Gy (retina), with the retina showing the highest odds ratio (28.33). To ensure clinical relevance, KCS was diagnosed based on decreased tear production combined with corneal damage to ensure clinical relevance. This study proposes dose thresholds for ocular structures that may guide treatment planning and reduce the risk of KCS in canine patients undergoing IMRT. Further prospective studies are warranted to validate these thresholds and explore mitigation strategies for high-risk cases. Full article

Background/Objectives: Taste dysfunction is a highly prevalent yet underrecognized complication among patients with head and neck cancer (HNC), significantly impairing nutritional intake, treatment adherence, and quality of life (QoL). This comprehensive review synthesizes current knowledge on the pathophysiological mechanisms and clinical management of taste dysfunction associated with HNC and its treatments, particularly chemotherapy and radiotherapy. Methods: A structured literature search was performed across PubMed, Scopus, and Cochrane Library for articles published between January 2015 and February 2025. Studies were included if they investigated taste dysfunction related to HNC, focusing on pathophysiological mechanisms and therapeutic interventions. A total of 47 original studies were analyzed through a narrative synthesis due to heterogeneity in study designs and outcomes. Results: Taste dysfunction in HNC patients arises from tumor-related inflammation, cytotoxic injury from chemotherapy, and radiation-induced epithelial and neural damage. Chemotherapy and radiotherapy often exert synergistic negative effects on gustatory function. Management strategies identified include dietary counselling, nutritional supplementation (zinc, lactoferrin, monosodium glutamate, miraculin), pharmacological agents targeting salivary function, and non-pharmacological interventions such as acupuncture, photobiomodulation, and reconstructive surgery. However, the evidence is limited by small sample sizes, methodological variability, and the frequent exclusion of HNC patients from broader dysgeusia trials. Reported prevalence of taste dysfunction ranged from 39% to 97.4%, with higher rates observed among patients treated with radiotherapy and chemoradiotherapy. Conclusions: Taste dysfunction remains a critical yet unmet clinical challenge in HNC patients. High-quality, targeted research is urgently needed to develop standardized assessments and evidence-based management strategies to improve patient outcomes. Full article

Breast cancer detection through non-invasive and accurate techniques remains a critical challenge in medical diagnostics. This study introduces a deep learning-based framework that leverages a microwave radar system equipped with an arc-shaped array of six antennas to estimate key tumor parameters, including position, size, and depth. This research begins with the evolutionary design of an ultra-wideband octagram ring patch antenna optimized for enhanced tumor detection sensitivity in directional near-field coupling scenarios. The antenna is fabricated and experimentally evaluated, with its performance validated through S-parameter measurements, far-field radiation characterization, and efficiency analysis to ensure effective signal propagation and interaction with breast tissue. Specific Absorption Rate (SAR) distributions within breast tissues are comprehensively assessed, and power adjustment strategies are implemented to comply with electromagnetic exposure safety limits. The dataset for the deep learning model comprises simulated self and mutual S-parameters capturing tumor-induced variations over a broad frequency spectrum. A core innovation of this work is the development of the Attention-Based Feature Separation (ABFS) model, which dynamically identifies optimal frequency sub-bands and disentangles discriminative features tailored to each tumor parameter. A multi-branch neural network processes these features to achieve precise tumor localization and size estimation. Compared to conventional attention mechanisms, the proposed ABFS architecture demonstrates superior prediction accuracy and interpretability. The proposed approach achieves high estimation accuracy and computational efficiency in simulation studies, underscoring the promise of integrating deep learning with conformal microwave imaging for safe, effective, and non-invasive breast cancer detection. Full article

Radiation therapy serves as a fundamental treatment for primary and metastatic brain tumors, whether used alone or combined with surgery and chemotherapy. Despite its oncological efficacy, this treatment paradigm frequently induces radiation-induced brain injury (RBI), a progressive neuropathological condition characterized by structural and functional damage to healthy cerebral parenchyma. Patients with RBI frequently develop affective disorders, particularly major depressive disorder and generalized anxiety disorder, which profoundly impair psychosocial functioning and quality of life. The pathophysiology involves complex mechanisms such as neuroinflammation, oxidative stress, blood–brain barrier disruption, and white matter damage. Current management strategies include antidepressants, corticosteroids, and neuroprotective agents, while emerging therapies targeting neuroinflammation and neural repair show promise. This review comprehensively examines the pathogenesis of RBI-related affective disorders and evaluates both conventional and novel treatment approaches. By synthesizing current evidence, we aim to provide insights for developing more effective interventions to improve patient outcomes and quality of life. Full article

Targeted radionuclide therapy (TRT) utilizes radiopharmaceuticals to deliver radiation directly to cancer cells while sparing healthy tissues. Beyond the absorbed dose of ablative radiation, TRT induces non-targeted effects (NTEs) that significantly enhance its therapeutic efficacy. These effects include radiation-induced bystander effects (RIBEs), abscopal effects (AEs), radiation-induced genomic instability (RIGI), and adaptive responses, which collectively influence the behavior of cancer cells and the tumor microenvironment (TME). TRT also modulates immune responses, promoting immune-mediated cell death and enhancing the efficacy of combination therapies, such as the use of immune checkpoint inhibitors. The molecular mechanisms underlying TRT involve DNA damage, oxidative stress, and apoptosis, with repair pathways like homologous recombination (HR) and non-homologous end joining (NHEJ) playing critical roles. However, challenges such as tumor heterogeneity, hypoxia, and radioresistance limit the effectiveness of this approach. Advances in theranostics, which integrate diagnostic imaging with TRT, have enabled personalized treatment approaches, while artificial intelligence and improved dosimetry offer potential for treatment optimization. Despite the significant survival benefits of TRT in prostate cancer and neuroendocrine tumors, 30–40% of patients remain unresponsive, which highlights the need for further research into molecular pathways, long-term effects, and combined therapies. This review outlines the dual mechanisms of TRT, direct toxicity and NTEs, and discusses strategies to enhance its efficacy and expand its use in oncology. Full article

Background/Objectives: Radiotherapy (RT) is a mainstay of clinical cancer therapy that causes broad immune responses. The complement system is a pivotal effector mechanism in the innate immune response, but the impact of RT is less well understood. This study investigates the interaction between RT and the complement system as a possible approach to improve immune responses in cancer treatment. Methods: Human solid cancer (lung, prostate, liver, breast cancer), lymphoma, and leukemia cells were irradiated using X-rays and treated with polyclonal antibodies or anti-CD20 monoclonal antibodies, respectively. Chromium release assay was applied to measure cell lysis after radiation with or without complement-activating antibody treatment. The expression of membrane-bound complement regulatory proteins (mCRPs; CD46, CD55, CD59), which confer resistance against complement activation, CD20 expression, apoptosis, and radiation-induced DNA double-strand breaks (γH2AX), was measured by flow cytometry. The radiosensitivity of tumor cells was assessed by colony-forming assay. Results: We demonstrate that RT profoundly impacts complement function by upregulating the expression of membrane-bound complement regulatory proteins (mCRPs) on tumor cells in a dose- and time-dependent manner. Impaired complement-mediated tumor cell lysis could thus potentially contribute to radiotherapeutic resistance. We also observed RT-induced upregulation of CD20 expression on lymphoma and leukemic cells. Notably, complement activation prior to RT proved more effective in inducing RT-dependent early apoptosis compared to post-irradiation treatment. While complement modulation does not significantly alter RT-induced DNA-damage repair mechanisms or intrinsic radiosensitivity in cancer cells, our results suggest that combining RT with complement-based anti-cancer therapy may enhance complement-dependent cytotoxicity (CDC) and apoptosis in tumor cells. Conclusions: This study sheds light on the complex interplay between RT and the complement system, offering insights into potential novel combinatorial therapeutic strategies and a potential sequential structure for certain tumor types. Full article

Malignant peripheral nerve sheath tumors (MPNSTs) are a rare type of soft tissue sarcoma associated with poor prognoses. The standard of care for non-resectable tumors consists of surgical excision followed by radiation and chemotherapy. MPNSTs are most common in patients with neurofibromatosis type 1 but can also occur sporadically. Regardless of origin, MPNSTs most often rely on signaling pathways that increase basal oxidative stress. This provides the basis for developing therapeutics with mechanisms that can potentiate oxidative stress to selectively eradicate tumor cells at doses that are tolerable for normal cells. Artemisinin derivatives are a mainstay of malaria therapy worldwide, with a well-established safety profile. Artemisinin’s antimalarial effects are due to an endoperoxide bridge in its chemical structure that induces oxidative stress. We found that artesunate (ARS) and metabolite dihydroartemisinin (DHA) are selectively cytotoxic to MPNST cells relative to normal Schwann cells with the endoperoxide bridge required for activity. Mechanistically, DHA induced oxidative stress, lipid peroxidation, and DHA-mediated cytotoxicity could be prevented with co-administration of the antioxidant N-acetyl-cysteine. Furthermore, we found that DHA was able to selectively remove MPNST from co-culture with normal Schwann cells. These data supports the further development of artemisinins for the clinical management of MPNST. Full article

Nanotechnology has significantly advanced cancer therapy, particularly through the development of multifunctional nanoparticles (NPs) capable of acting as both therapeutic and diagnostic agents. This review focuses on the synergistic integration of radiotherapy (RT) and photothermal therapy (PTT) mediated by engineered NPs—a rapidly evolving strategy that enhances tumor specificity, minimizes healthy tissue damage, and enables real-time imaging. By analyzing the recent literature, we highlight the dual role of NPs in amplifying radiation-induced DNA damage and converting near-infrared (NIR) light into localized thermal energy. The review classifies various metal-based and composite nanomaterials (e.g., Au, Pt, Bi, Cu, and Fe) and evaluates their performance in preclinical RT–PTT settings. We also discuss the physicochemical properties, targeting strategies, and theragnostic applications that contribute to treatment efficiency. Unlike conventional combinatorial therapies, NP-mediated RT–PTT enables high spatial–temporal control, immunogenic potential, and integration with multimodal imaging. We conclude with the current challenges, translational barriers, and outlooks for clinical implementation. This work provides a comprehensive, up-to-date synthesis of NP-assisted RT–PTT as a powerful approach within the emerging field of nano-oncology. Full article

Magnesium (Mg²⁺) has gained oncologists’ attention due to its wide range of biological functions and frequent use as a complementary or integrative agent. This review outlines Mg’s actions, its complex role in carcinogenesis and tumor risk, and clinical issues. Mg²⁺ is essential in numerous biochemical processes, including adenosine triphosphate production, cellular signal transduction, DNA, RNA and protein synthesis, and bone formation. Pertinent full-text articles were thoroughly examined, and the most relevant ones were selected for inclusion in this review. There is conflicting scientific evidence about the relationship between Mg²⁺ changes and cancer risk, apart from colorectal cancer. Chronic Mg²⁺ deficiency leads to immune dysfunctions and enhanced baseline inflammation associated with oxidative stress related to various age-associated morbidities and cancer. On the other hand, Mg²⁺ deficiency is associated with drug or chemotherapy-related hypomagnesemia, postoperative pain, cachexia, opioid-induced constipation, normal tissue protection from radiation damage, and prevention of nephrotoxicity. A balanced diet usually provides sufficient Mg²⁺, but supplementation may be necessary in some clinical settings. Full article

Exposure to high-linear energy transfer (LET) heavy ions, such as ²⁸Si, poses a significant cancer risk for astronauts. While previous studies have linked high-LET radiation exposure to persistent oxidative stress and dysregulated stress responses in intestinal crypt cells with an increased risk of tumorigenesis, the relationship between IR-induced oxidative DNA damage and intestinal cancer risk remains incompletely understood. Here, we investigated the time-dependent effects of ²⁸Si-ion radiation on intestinal tumorigenesis and oxidative DNA damage in Apc^1638N/+ mice, a model for human intestinal cancer predisposition. Male Apc^1638N/+ mice were exposed to 10 cGy of either γ-rays (low-LET) or ²⁸Si-ions (high-LET), and intestinal tumor burden was assessed at 60 and 150 days post-irradiation. While both radiation groups showed modest, non-significant tumor increases at 60 days, ²⁸Si-irradiated mice exhibited an approximately 2.5-fold increase in tumor incidence by 150 days, with a higher incidence of invasive carcinomas compared to γ and sham groups. Serum 8-OxodG levels, a marker of systemic oxidative stress, were significantly elevated in the ²⁸Si-ion group, correlating with increased intestinal 8-OxodG staining. Additionally, assessment of the proliferation marker Cyclin D1 and metaplasia marker Guanylyl Cyclase C (GUCY2C) also revealed significant crypt cell hyperproliferation accompanied by increased metaplasia in ²⁸Si-exposed mouse intestines. Positive correlations between serum 8-OxodG and tumor-associated endpoints provide compelling evidence that exposure to ²⁸Si-ions induces progressive intestinal tumorigenesis through sustained oxidative DNA damage, crypt cell hyperproliferation, and metaplastic transformation. This study provides evidence in support of the radiation quality-dependent progressive increase in systemic and intestinal levels of 8-OxodG during intestinal carcinogenesis. Moreover, the progressive increase in oxidative DNA damage and simultaneous increase in oncogenic events after ²⁸Si exposure also suggest that non-targeted effects might be a significant player in space radiation-induced intestinal cancer development. The correlation between serum 8-OxodG and oncogenic endpoints supports its potential utility as a predictive biomarker of high-LET IR-induced intestinal carcinogenesis, with implications for astronaut health risk monitoring during long-duration space missions. Full article

Objectives: Beta-emitting radionuclide therapy, exemplified by ¹⁷⁷Lu-Oxodotreotide (Lutathera^®), enables targeted treatment of neuroendocrine tumors by delivering β-radiation to tumor cells. However, the dose-dependent molecular mechanisms underlying cellular damage remain insufficiently characterized. This study aimed to investigate the phenotypic changes in IMR-32 human neuroblastoma cells following Lutathera exposure, with a focus on the dose-dependent relationship between radiation and cellular damage. Methods: IMR-32 cells were allocated to control, low- (0.05 MBq/mL), medium- (0.5 MBq/mL), and high-dose (5 MBq/mL) groups and treated with ¹⁷⁷Lu-Oxodotreotide for 24 h. Flow cytometry was employed to assess cell viability, apoptosis, mitochondrial membrane potential, γ-H2AX expression (a marker of DNA damage), and proliferation. Results: Lutathera induced dose-dependent cytotoxic effects. Cell viability declined linearly with increasing dose (control: 100% vs. high-dose: 13.48%; r = −0.955, p < 0.001). Apoptosis was significantly elevated (control: 35.34% vs. high-dose: 88.12%; r = 0.999), accompanied by increased γ-H2AX levels (control: 5.26 × 10⁴ vs. high-dose: 13.13 × 10⁴; r = 0.930), indicating DNA double-strand breaks. Mitochondrial membrane potential decreased (control: 6.06 × 10⁴ vs. high-dose: 46.27 × 10⁴; r = 0.999), and proliferation was suppressed (control: 91.10 × 10⁴ vs. high-dose: 103.84 × 10⁴; r = 0.954), both showing strong dose correlations (p < 0.001). Conclusions: ¹⁷⁷Lu-Oxodotreotide exerts dose-dependent cytotoxicity in IMR-32 cells via DNA damage, mitochondrial dysfunction, and apoptosis induction. These findings underscore the necessity of optimizing dosing regimens to balance therapeutic efficacy and safety in clinical settings, providing a foundation for personalized β-emitter therapies. Full article

Background: The use of nanoradiosensitizers is a promising strategy for the precision enhancement of tumor tissue damage during radiotherapy. Methods: Here, we propose a novel biocompatible theranostic agent based on gadolinium fluoride doped with cerium and terbium (Gd_0.7Ce_0.2Tb_0.1F₃ NPs), which showed pronounced radiocatalytic activity when exposed to photon or proton beam irradiation, as well as remarkable MRI contrast ability. A scheme for the production of biocompatible colloidally stable Gd_0.7Ce_0.2Tb_0.1F₃ NPs was developed. Comprehensive physicochemical characterization of these NPs was carried out, including TEM, SEM, XRD, DLS, and EDX analyses, as well as UV–vis spectroscopy and MRI relaxation assays. Results: Cytotoxicity analysis of Gd_0.7Ce_0.2Tb_0.1F₃ NPs in vitro and in vivo revealed a high level of biocompatibility. It was shown that Gd_0.7Ce_0.2Tb_0.1F₃ NPs effectively accumulate in MCF-7 tumor cells. A study of their radiosensitizing activity demonstrated that the combined effect of Gd_0.7Ce_0.2Tb_0.1F₃ NPs and X-ray irradiation leads to a dose-dependent decrease in mitochondrial membrane potential, a sharp increase in the level of intracellular ROS, and the subsequent development of radiation-induced apoptosis. Conclusions: This outstanding radiosensitizing effect is explained by the radiocatalytic generation of reactive oxygen species by the nanoparticles, which goes beyond direct physical dose enhancement. It emphasizes the importance of evaluating the molecular mechanisms underlying the sensitizing effectiveness of potential nanoradiosensitizers before choosing conditions for their testing in in vivo models. Full article

Stereotactic body radiotherapy (SBRT) delivers ablative radiation doses with sub-millimeter precision. Radiogenomic studies, meanwhile, provide insights into how tumor-intrinsic genetic factors influence responses to such high-dose treatments. This review explores the radiobiological mechanisms underpinning SBRT efficacy, emphasizing the roles of DNA damage response (DDR) pathways, tumor suppressor gene alterations, and inflammatory signaling in shaping tumor radiosensitivity or resistance. SBRT induces complex DNA double-strand breaks (DSBs) that robustly activate DDR signaling cascades, particularly via the ATM and ATR kinases. Tumors with proficient DNA repair capabilities often resist SBRT, whereas deficiencies in key repair genes can render them more susceptible to radiation-induced cytotoxicity. Mutations in tumor suppressor genes may impair p53-dependent apoptosis and disrupt cell cycle checkpoints, allowing malignant cells to evade radiation-induced cell death. Furthermore, SBRT provokes the release of pro-inflammatory cytokines and activates innate immune pathways, potentially leading to immunogenic cell death and reshaping the tumor microenvironment. Radiogenomic profiling has identified genomic alterations and molecular signatures associated with differential responses to SBRT and immune activation. These insights open avenues for precision radiotherapy approaches, including the use of genomic biomarkers for patient selection, the integration of SBRT with DDR inhibitors or immunotherapies, and the customization of treatment plans based on individual tumor genotypes and immune landscapes. Ultimately, these strategies aim to enhance SBRT efficacy and improve clinical outcomes through biologically tailored treatment. This review provides a comprehensive summary of current knowledge on the genetic determinants of response to stereotactic radiotherapy and discusses their implications for personalized cancer treatment. Full article

Background: Breast cancer (BC) is the most common cancer in women worldwide. Much progress has been made to improve treatment options for patients suffering from the disease, including a novel therapy—Poly (ADP-ribose) polymerase inhibitor (PARPi) that specifically targets tumors with deficiencies in the Homologous Recombination (HR) DNA repair pathway. To benefit better from conventional therapy, many patients seek alternative supplementation, with 20–30% of cancer patients using herbal medication on top of their regular treatment. An example of such easily available over-the-counter supplements is curcumin, a natural compound derived from turmeric (Curcuma longa). Various studies reported the potential HR deficiency (HRD) inducing effect of curcumin in cancer cells. Methods: Eight BrC and three normal cell lines and a BrC PDX model were used to evaluate the effect of curcumin on RAD51 ionizing radiation-induced focus (IRIF) formation. Three breast BrC cell lines underwent further analysis using the BRCA2 Western blot technique. To assess cell survival after treatment with curcumin and/or PARPi, a clonogenic survival assay was performed on both normal and cancerous cell lines. Results: Curcumin treatment led to a reduction in RAD51 IRIF formation capacity across all tested models. A decrease in BRCA2 levels was observed in the tested cell lines. Our findings demonstrate that HRD can be induced in both cancerous and normal cells, suggesting that curcumin treatment may increase the risk of toxicity when combined with PARPi therapy. Conclusions: The use of curcumin in combination with certain anti-cancer treatments should not be implemented without extensive monitoring for deleterious side effects. Full article

Multidrug resistance (MDR) represents a major obstacle to successful chemotherapy and, due to overlapping defense mechanisms, such as enhanced DNA repair and the evasion of apoptosis, can also be associated with radioresistance. In this study, we investigated whether MDR breast cancer cells (MCF-7/CMF) exhibit reduced susceptibility to radiation-induced DNA fragmentation compared to their non-resistant parental counterpart (MCF-7). Using a nucleosome-based ELISA, we quantified the chromatin fragmentation in MCF-7 and MCF-7/CMF cells following their exposure to four radiopharmaceuticals: [^99mTc]pertechnetate, [¹³¹I]NaI (sodium iodide), [¹²⁵I]NaI, and the DNA-incorporating compound [¹²⁵I]iododeoxyuridine ([¹²⁵I]IdU). Each radioactive preparation was assessed across a range of activity concentrations, using a two-way ANOVA. For [^99mTc]pertechnetate and [¹³¹I]NaI, significantly higher DNA fragmentation was observed in the sensitive cell line, whereas [¹²⁵I]NaI showed no significant difference between the two phenotypes. In contrast to the other radiopharmaceuticals, [¹²⁵I]IdU induced greater fragmentation in resistant cells. This finding was supported by the statistical analysis (a 63.7% increase) and visualized in the corresponding dose–response plots. These results highlight the critical role of the intranuclear enrichment of Auger emitters and support further development of radiopharmaceuticals in accordance with this principle. Our data suggest that radiotoxicity is governed not by linear energy transfer (LET) alone, but, fundamentally, by the spatial proximity of the radionuclide to the DNA. Targeting tumor cell DNA with precision radiotherapeutics may, therefore, offer a rational strategy to overcome MDR in breast cancer. Full article