Abstract: Background: Radiotherapy is an essential component for the treatment of skull skull‑base tumours. However, radiation‑induced brain injury (RIBI) appearing on magnetic resonance imaging (MRI) as pseudoprogression, radiation‑induced contrast enhancement (RICE), radiation necrosis, and other contrast‑enhancing brain lesions—remains an important late toxicity which is not very well characterized. Clarifying adult‑specific patterns, the role of positron emission tomography (PET), and differences between proton and photon therapy is clinically relevant. Methods: Narrative review of peer‑reviewed literature to 1 October 2025 focused on adult chordoma, chondrosarcoma, meningioma, adenoid cystic carcinoma, pituitary adenoma, craniopharyngioma, undifferentiated carcinoma of nasopharyngeal type (UCNT), and germinoma. Results: Radiation-induced brain injury (RIBI) may range from early transient brain oedema/enhancement to late necrosis. Lesions cluster in temporal and frontal lobes after skull‑base irradiation. Proton therapy generally reduces high‑dose exposure versus photons and is associated with fewer severe necrotic events, though asymptomatic RICE is common. Advanced MRI (diffusion, perfusion, spectroscopy, ASL, amide proton transfer) and positron emission tomography (PET) with Fluorodeoxyglucose (FDG) and amino‑acid tracers aid distinction between treatment effect and progression. Risk reflects dose–volume metrics, prior irradiation, and patient comorbidities. Conclusions: MRI/PET alterations after skull‑base radiotherapy vary by modality, dose, and tumor context. Integrating multimodal imaging with clinical factors should guide surveillance and management; prospective validation is needed.

Abstract: Older adults with cancer face disproportionately high rates of severe treatment-related toxicities, yet current prediction tools rarely incorporate biomarkers that capture physiological resilience. The hypothalamic–pituitary–adrenal (HPA) axis—central to stress adaptation, immune regulation, and tissue repair—undergoes pronounced age-related alterations, including elevated basal cortisol, reduced dehydroepiandrosterone (DHEA) and its sulphate form DHEAS, and an increased cortisol:DHEA(S) ratio. These changes may impair immune function, delay recovery, and exacerbate vulnerability to treatment toxicity. This narrative review synthesizes mechanistic and clinical evidence linking HPA-axis dysregulation to treatment tolerance in geriatric oncology. Common patterns include blunted diurnal cortisol slopes, elevated evening cortisol, and low DHEA(S), which are associated with fatigue, functional decline, and reduced survival across cancer types. However, their predictive value for acute treatment toxicities remains underexplored due to methodological heterogeneity, lack of age-specific reference ranges, and absence from existing geriatric toxicity models. This review proposes a translational roadmap that prioritizes (1) standardization of salivary cortisol/DHEA(S) protocols; (2) prospective, age-stratified validation studies using standardized toxicity endpoints; (3) interventional testing of behavioral or pharmacological strategies to modulate HPA function; and (4) integration into oncology workflows and electronic decision-support tools. Incorporating endocrine biomarkers into risk prediction could refine treatment stratification, enable targeted supportive care, and ultimately improve outcomes for older patients with cancer.

Abstract: Background/Objectives: Repetitive magnetic stimulation (rMS) and static magnetic stimulation (sMS) are currently used as adjunctive therapies for certain neurological conditions. Despite substantial advances in cancer treatment, unfavorable prognoses and outcomes persist, especially for aggressive neoplasms, including glioblastoma and acute myeloid leukemia. In this context, the application of magnetic fields has demonstrated significant anti-tumoral benefits in both in vitro and animal studies, indicating its potential as an effective non-invasive therapeutic strategy; nevertheless, the precise mechanisms of action remain unclear. This scoping review was intended to identify published research investigating the effects of sMS and rMS in in vitro and in vivo models to evaluate their impacts on morphological and molecular parameters. Methods: Four databases (PubMed, Embase, Web of Science, and Scopus) were assessed; the search strategy was limited to the past twenty-five years of data publication. Studies employing rMS or sMS as a primary therapy for conditions apart from neoplasms, and those not addressing these interventions as an adjuvant therapy were excluded. Results: Nine articles using rMS were included: three in vitro, two employing animal models, and the remaining four including both cellular and animal-based analyses. Seventeen studies using sMS were identified: thirteen in vitro and four in vivo. Conclusions: This review indicates that sMS and rMS are employed as adjuvant therapies for increasing the efficacy of conventional drugs like chemotherapy. Their efficacy relies on specific factors: type of cancer, location, cell type, metabolism, and exposure parameters, including intensity, frequency, and duration.

Abstract: Triple-negative breast cancer (TNBC) is an aggressive malignancy that disproportionately affects young women. The integration of immune checkpoint inhibitors (ICIs) has significantly improved outcomes in both early-stage and metastatic TNBC, shifting attention toward long-term survivorship issues, particularly endocrine function and fertility. However, the reproductive safety profile of ICIs remains insufficiently characterized. This narrative review synthesizes current preclinical and clinical evidence on ICI-associated reproductive toxicity, focusing on both direct immune-mediated gonadal injury and indirect disruption of the hypothalamic–pituitary–gonadal axis. Experimental models consistently demonstrate immune cell infiltration of ovarian and testicular tissue, cytokine-driven inflammatory cascades, follicular atresia, impaired spermatogenesis, and altered steroidogenesis following PD-1/PD-L1 and CTLA-4 blockade. Emerging clinical data report cases of immune-related orchitis, azoospermia, testosterone deficiency, diminished ovarian reserve, and premature ovarian insufficiency. Secondary hypogonadism due to immune-mediated hypophysitis represents an additional and frequently underdiagnosed mechanism. We further discuss the oncofertility challenges faced by young patients with TNBC treated with chemoimmunotherapy, emphasizing the uncertainty of fertility risk stratification and the importance of early fertility counseling and individualized fertility preservation strategies. To illustrate the potential clinical impact, we present the case of a 34-year-old nulliparous woman who developed premature ovarian insufficiency two years after neoadjuvant chemoimmunotherapy including atezolizumab, despite ovarian suppression. In conclusion, while ICIs have transformed the therapeutic landscape of TNBC, their potential long-term impact on reproductive and endocrine health represents a clinically significant concern. A precautionary, multidisciplinary oncofertility approach and prospective clinical registries are essential to define the true incidence and mechanisms of ICI-associated reproductive toxicity.

Abstract: Background: In triple-negative breast cancer (TNBC), the addition of immunotherapy has significantly improved outcomes. Immune-related adverse events (irAEs) can be accelerated in patients with pre-existing autoimmune (AI) conditions. The treatment-response standardised protocol used in clinical care raises concerns about the need for right-sizing strategies. As the use of immunotherapy expands, recognising toxicity from recurrence and optimising response-adapted approaches are essential to balance cure with quality of survival. Case Presentation: A 38-year-old pregnant woman with a distant history of uveitis and psoriasis was discovered to have pregnancy-associated TNBC. Postnatally, she was treated with neoadjuvant chemotherapy and pembrolizumab, followed by wire-guided left breast wide local excision and sentinel lymph node biopsy of left axilla. After surgery, residual cancer was noted. She continued adjuvant pembrolizumab and adjuvant radiotherapy 40.05Gy/15fr to the breast and nodes, followed by 13.35Gy/5fr. Despite a persistent residual tumour, pembrolizumab was continued as per protocol in a response-agnostic manner. At the end of one year of adjuvant pembrolizumab, she developed progressive numbness and weakness in the ipsilateral arm, initially raising suspicion for local recurrence. Comprehensive MRI and PET-CT imaging did not identify recurrent tumour or new metastatic disease. Electromyography confirmed a lower-trunk brachial plexopathy without a structural cause. An immune-mediated process was diagnosed by a process of elimination. Despite treatment with 1st-line high-dose corticosteroids and 2nd-line intravenous immunoglobulin (IVIG), improvement was limited. Therapeutic plasmapheresis, theoretically removing circulating immune complexes, cytokines, or checkpoint inhibitors, led to marked functional recovery and symptom resolution 20 months later. Discussion: Four main challenges are identified: (1) the diagnostic difficulty in identifying local recurrence or radiation injury from immune-related neuropathy; (2) the emerging therapeutic role of plasmapheresis in steroid-refractory irAEs; (3) the possible inconsistencies between rare toxicities observed in clinical trials vs clinical practice; and (4) the limitations in response in adjuvant therapy, particularly in patients with coexisting AI conditions. Conclusion: Although N-irAEs are rare, survival in early TNBC declines markedly when they occur during treatment. Early recognition and accurate distinction from tumour recurrence, as well as support for plasmapheresis as a potential option in steroid-refractory presentations, have been shown to improve patient survival and symptom reduction. With increasing use of immunotherapy, real-world toxicity data, predictive biomarkers, and personalised treatment strategies are urgently needed to balance cure with long-term functional outcomes.

Abstract: Background/Objectives: Digital health encompasses telemedicine, mobile health (mHealth), wearable technologies, big data analytics, artificial intelligence (AI), machine learning (ML), and immersive technologies. In oncology, where care is complex, multidisciplinary, and longitudinal, these tools offer opportunities to enhance prevention, early detection, treatment planning, patient–clinician communication, survivorship, and palliative care. However, inconsistent definitions and ongoing ethical, regulatory, and implementation challenges hinder optimal integration. This review aims to synthesize current evidence on digital health in oncology and examine its applications across the cancer care continuum. Methods: A comprehensive narrative review of peer-reviewed literature was conducted, including clinical studies, trials, and systematic reviews evaluating digital health technologies in oncology. Evidence was organized according to key phases of the cancer care continuum, from prevention and diagnosis to treatment delivery, survivorship, and end-of-life care. Results: Digital health applications extend beyond virtual consultations. AI- and ML-driven systems support diagnostics, medical imaging, genomics, and treatment planning, while mHealth applications and wearable devices enable real-time symptom monitoring, toxicity reporting, and long-term follow-up. Digital education and communication platforms improve shared decision-making and patient engagement. Across diverse oncology settings, these tools demonstrate feasibility, high patient and clinician satisfaction, and potential improvements in care coordination and efficiency. Nevertheless, challenges related to data quality, interoperability, privacy, algorithmic bias, equity of access, and regulatory oversight persist. Conclusions: Digital health is increasingly embedded across the oncology care continuum and holds substantial promise for advancing personalized, patient-centred cancer care. Continued multidisciplinary collaboration, robust clinical validation, and responsible governance are essential to ensure safe, equitable, and clinically meaningful global implementation.

Abstract: Autophagy is a highly conserved cellular degradation process essential for maintaining cellular homeostasis, yet its role in cancer is fundamentally context dependent. Increasing evidence indicates that autophagy suppresses tumor initiation by preserving genomic and metabolic integrity, while paradoxically supporting tumor progression, therapy resistance, and immune evasion at advanced stages. This functional duality presents a major challenge for therapeutic targeting and largely reflects the spatiotemporal heterogeneity of autophagy regulation across tumor stages, cancer cell subpopulations, and the tumor microenvironment (TME). In this review, we argue that autophagy-related proteins should be conceptualized as context-dependent therapeutic nodes rather than universally actionable targets. We systematically examine key autophagy regulators—including Beclin-1, p62/SQSTM1, mTOR, and p53， and analyze how their functions are shaped by tumor stage, genetic background, and microenvironmental cues such as hypoxia, immune pressure, and stromal interactions. We further highlight the pivotal role of the TME in determining autophagy dependency and therapeutic vulnerability, providing mechanistic insight into why autophagy modulation without microenvironmental consideration often yields inconsistent outcomes. From a precision medicine perspective, we discuss how nanotechnology-based delivery systems enable spatially and temporally controlled modulation of autophagy, thereby addressing intratumoral heterogeneity and reducing systemic toxicity. By integrating molecular profiling, TME characteristics, and nanomedicine-enabled targeting strategies, this review outlines a rational framework for exploiting autophagy in cancer therapy. Together, these insights provide a foundation for the development of context-aware, autophagy-targeted interventions and advance the pursuit of more effective and personalized cancer treatments.

Abstract:

Germline pathogenic variants influence breast cancer risk and clinical behavior, yet data from Indonesian populations remain scarce. In this pilot cross-sectional study, 31 newly diagnosed Indonesian women with luminal A or luminal B breast cancer underwent germline testing using a 113-gene hereditary cancer panel, with variants classified according to ACMG criteria and correlated with clinicopathological features. Pathogenic or likely pathogenic variants were identified in 9 of 31 patients (29.0%), most frequently involving BRCA2, PALB2, and RECQL4. A significantly higher frequency of pathogenic/likely pathogenic variants was observed among patients with mixed invasive histology (3/3) compared with those with invasive carcinoma of no special type (6/27; p = 0.019), and a positive first-degree family history of breast cancer was also associated with pathogenic/likely pathogenic variant status (p = 0.022). This study provides the first description of germline pathogenic variants in Indonesian luminal breast cancer and suggests that mixed invasive histology and first-degree family cancer history may represent enrichment signals for hereditary predisposition, warranting validation in larger cohorts.

Abstract: Lung cancer is one of the most commonly diagnosed cancers worldwide and remains the leading cause of cancer-related death in both men and women. In 2022, approximately 2.5 million new cases of lung cancer and 1.8 million deaths due to the disease were estimated. Historically, lung cancer has been more frequent in men, although the difference between sexes has been decreasing, with tobacco use remaining the main etiological factor. Survival rates vary considerably depending on the stage at diagnosis and other factors, and overall prognosis remains poor, with a relatively low five-year survival rate compared to other types of cancer. In this work, the objective is to present current approaches to lung cancer diagnosis through the study of multiple genetic alterations and biomarkers, mainly detected by next-generation sequencing (NGS), which has significantly transformed cancer diagnostics by enabling highthroughput and cost-effective genomic analysis. In the context of lung cancer, NGS plays a crucial role in improving molecular characterization, guiding targeted therapies, and supporting personalized medicine strategies. Specifically, its relevance lies in the ability to provide a comprehensive genomic profile of the tumor, identify driver mutations, predict treatment response, detect co-occurring alterations, and assist in therapeutic stratification. A real-world case study was conducted including 101 patients diagnosed with lung cancer between 2023 and 2025 in a reference laboratory, whose tumors were analyzed using NGS. The most frequently altered genes identified were KRAS, EGFR, and ALK, together with other less common but clinically actionable alterations, as well as the evaluation of programmed death-ligand 1 (PD-L1) expression by immunohistochemistry. In summary, next-generation sequencing represents a fundamental tool in the diagnostic workflow of lung cancer, enabling comprehensive molecular profiling that supports personalized treatment selection and contributes to improved clinical management of patients.

Abstract: A type II cadherin, Cadherin-19 (CDH19), plays a vital role in neural crest development. CDH19 regulates cell–cell junctions and migration by forming catenin-cytoskeleton complexes. Although anti-CDH19 monoclonal antibodies (mAbs) are used for specific applications such as Western blotting and immunohistochemistry (IHC), suitable anti-CDH19 mAbs for flow cytometry are limited. Here, novel anti-human CDH19 mAbs (Ca19Mabs) were developed through flow cytometry-based high-throughput screening. One clone, Ca19Mab-8 (IgG1, κ), specifically recognized CDH19-overexpressing Chinese hamster ovary-K1 cells but did not bind to other 21 CDHs (including both type I and type II) in flow cytometry. Additionally, Ca19Mab-8 recognized endogenous CDH19 in the human glioblastoma cell line LN229. The dissociation constant (KD) of Ca19Mab-8 for LN229/CDH19 was 9.0 × 10⁻⁹ M. Ca19Mab-8 can detect CDH19 in Western blotting and IHC. These findings suggest that Ca19Mab-8 is versatile for basic research and has potential applications in clinical diagnosis and tumor therapy.

Abstract: Background: Oncology medication costs are increasing internationally; patient attitudes towards these costs remain unclear. Methods: A three-part cross-sectional questionnaire was distributed to patients with breast cancer to determine their attitudes towards oncology medication costs and to ex-plore potential patient acceptable methods to reduce these costs. Results: 321 patients were eligible for inclusion and 180 fully completed the questionnaire (56.1% response rate). Overall, 67.8% (N = 122/180) of patients found the costs presented in the questionnaire to be unacceptable. 92.2% (N = 166/180), 87.8% (N = 158/180) and 68.9% (N = 124/180) of participants found the costs of pembrolizumab, palbociclib and trastuzumab respectively to be unacceptable. 72.8% (N = 131/180) of patients indicated that they would like to be better informed about the societal costs of their cancer treatment and 81.1% (N = 146/180) of patients believed that reducing the costs of cancer treatment to society is important. There was a statistically significant difference in patient desires to be better informed of societal drug costs between those with early-stage breast cancer and those with metastatic disease (75.8% vs 47.4%, χ2 = 6.923, p = 0.009). Conclusion: These findings indicate that many Irish patients with breast cancer find the societal costs of oncology medications to be unacceptable, and many patients have a de-sire to be better informed of these costs.

Abstract: Glioblastoma (GBM) remains among the most treatment-refractory human malignancies, shaped by profound molecular heterogeneity, extensive genomic instability and an immunosuppressive tumor microenvironment. Radiotherapy represents a cornerstone of current management; however, its therapeutic benefit is frequently limited by adaptive resistance and ineffective antitumor immunity. Emerging evidence indicates that ionizing radiation acts not only as a cytotoxic modality, but also as a potent immunological trigger through the release of damage-associated molecular patterns (DAMPs) and the induction of immunogenic cell death (ICD). In this review, we synthesize recent advances describing how canonical DAMPs—including HMGB1, ATP, calreticulin exposure, mitochondrial and nuclear DNA fragments—coordinate innate and adaptive immune activation via TLR-, RAGE- and cGAS–STING-dependent pathways. We further discuss the dual nature of DAMP signaling, which can either promote durable antitumor immunity or foster chronic inflammation, myeloid reprogramming and tumor tolerance, depending on radiation dose, fractionation, tumor context and concomitant therapies. Special emphasis is placed on how different radiation qualities, particularly proton versus photon irradiation, differentially modulate DAMP release, ICD dynamics and microenvironmental remodeling. Finally, we highlight translational opportunities to exploit DAMP-related signatures as liquid-biopsy biomarkers of response, as rational selectors for combination strategies (including immunotherapy and radiosensitizers), and as biological guides for personalized and adaptive radiotherapy in GBM. Collectively, DAMP-centered radiobiology provides a conceptual framework to integrate immunity into radiation planning and may enable a new generation of biologically informed treatment strategies for glioblastoma.

Abstract: Immunotherapy has transformed cancer management. Patients receiving immune checkpoint inhibitors frequently experience concurrent pain and sleep disturbances that affect quality of life, treatment adherence, and overall survival. Nursing interventions addressing both symptoms remain poorly defined. This scoping review searched the Scopus, ScienceDirect, PubMed, and CINAHL for updates from 2019 to 2025 following PRISMA-ScR guidelines; ten studies were included (randomized controlled trials, systematic reviews, and observational studies for all cancers since focusing on melanoma alone would not give enough results. Nurse-led interventions included education, physical therapies (massage, reflexology, acupressure), behavioral approaches, and digital platforms (telehealth, electronic patient-reported outcomes). The patients achieved moderate short-term pain reductions, significantly improved quality of life, enhanced treatment adherence, and reduced emergency department visits by up to 45%. However, only 2/10 studies used validated instruments to measure sleep quality, and none designed primary interventions specifically targeting sleep disturbances in patients receiving immunotherapy. Long-term sustainability of pain interventions was questionable, with most effects attenuating beyond eight weeks except for psycho-educational approaches. Future research should develop integrated, nurse-delivered interventions addressing pain and sleep as interconnected symptoms, with extended follow-up periods and enhanced accessibility across diverse healthcare settings. Validated instruments to measure sleep quality should be employed.

Abstract:

Background: Accurate prognostic assessment remains crucial in metastatic renal cell carcinoma (mRCC), especially as treatment options have expanded beyond vascular endothelial growth factor (VEGF)–targeted therapies to include immune checkpoint inhibitors (ICIs) and ICI–TKI combinations. The widely used IMDC classification shows important limitations in the modern therapeutic era, highlighting the need for complementary prognostic tools. In this context, the Meet-URO and CANLPH scores—incorporating clinical, inflammatory, and nutritional markers have emerged as promising alternatives. Objective: To evaluate and compare the prognostic performance of the Meet-URO and CANLPH scoring systems in a real-world mRCC cohort predominantly treated with first-line tyrosine kinase inhibitor (TKI) monotherapy due to limited access to ICI-based combinations. Methods: This retrospective single-center study included 112 patients with mRCC. The Meet-URO score was calculated for all patients, while the CANLPH score was assessed in 56 patients with complete laboratory data. CAR, NLR, and PHR were computed using baseline pre-treatment measurements. Overall survival (OS) and progression-free survival (PFS) the latter defined exclusively for first-line therapy—were estimated using the Kaplan–Meier method. Correlations between inflammatory markers and survival outcomes were analyzed using Spearman’s rho. Results: Meet-URO demonstrated clear prognostic stratification across all five categories, with the most favorable outcomes in score group 2 and progressively poorer OS and PFS in higher-risk groups. CANLPH also showed meaningful survival discrimination, with the highest inflammatory group (score 3) exhibiting markedly reduced OS and PFS. CAR was the strongest individual predictor of survival, while NLR and PHR showed weaker associations. Conclusion: Both Meet-URO and CANLPH provide strong, complementary prognostic information in mRCC, even in a cohort largely treated with TKI monotherapy. Their integration into routine risk assessment may enhance clinical decision-making, particularly in resource-limited settings.

Abstract: Background/Objectives: Nutritional risk screening is critical in the management of gynaecologic oncology (GO) surgical patients. Malnutrition is prevalent in this population and is associated with poorer surgical outcomes, including increased morbidity, prolonged hospital stays, and reduced survival rates. Nevertheless, the optimal nutritional screening tools for this patient group remain undefined. Methods: We conducted a narrative review to critically appraise commonly used nutritional screening and assessment tools in surgical GO patients. To highlight practical challenges in accurately identifying at-risk individuals, we incorporated findings from our recent clinical audit. Results: Several nutritional screening and assessment tools were identified. The results varied considerably between tools. The presence of ascites and rapid deterioration in oral intake were frequently overlooked, leading to under-recognition of malnutrition. These issues were corroborated by our audit findings. Emerging strategies including determining body composition from routine preoperative CT scans show promise. Conclusions: Accurate nutritional assessment is imperative to improve surgical outcomes in surgical GO patients. As currently no gold standard currently exists for this population, bespoke approaches to address disease-specific nutritional considerations are urgently needed to identify those at risk and allow for timely nutritional interventions. Integrating CT-based body composition analysis can provide an objective solution, thus requiring further investigation.

Abstract:

Background/Objectives: The anti-CLDN18.2 antibody zolbetuximab has emerged as a novel therapeutic option for advanced gastric adenocarcinoma. However, robust predictive biomarkers for its efficacy remain an unmet need. Methods: Utilizing the Japanese Center for Cancer Genomics and Advanced Therapeutics database, we retrospectively analyzed the clinical and genomic profiles of 49 patients with gastric adenocarcinoma who received zolbetuximab-containing regimens. Due to Japanese health insurance regulations, these patients were deemed to have CLDN18.2-positive tumors. We explored the association between objective response rate (ORR) and concurrent genomic alterations, focusing on tumor mutational burden (TMB) and major mutations (TP53, ARID1A, CDH1). Results: The ORR to zolbetuximab-based therapy in this cohort was 22.2%. Statistical analysis revealed a trend toward higher clinical response in patients with lower TMB (median 1.82 in responders vs. 4.0 in non-responders; p=0.050). Furthermore, patients without a CDH1 single nucleotide variant also showed a suggestive trend toward better response (p=0.086). No significant associations were found with TP53 or ARID1A alterations (p=0.787 and p=0.239, respectively). Conclusions: Our findings suggest that low TMB and the absence of CDH1 variants may serve as potential predictive biomarkers for response to zolbetuximab in CLDN18.2-positive gastric cancer. Prospective validation is warranted to maximize patient selection for this targeted therapy.

Abstract: Cancer remains a leading cause of morbidity and mortality worldwide, and effective strategies for cancer prevention are urgently needed to complement therapeutic ad-vances. While dietary factors are known to influence cancer risk, the molecular mecha-nisms that mediate inter-individual responses to nutritional exposures remain poorly defined. Emerging evidence identifies long non-coding RNAs (lncRNAs) as pivotal regulators of gene expression, chromatin organization, metabolic homeostasis, immune signaling, and cellular stress responses, core processes that drive cancer initiation and progression and are highly sensitive to nutritional status. In parallel, advances in pre-cision nutrition have highlighted how variability in genetics, metabolism, microbiome composition, and epigenetic landscapes shapes dietary influences on cancer susceptibility. This review integrates these rapidly evolving fields by positioning lncRNAs as molecular conduits that translate dietary exposures into transcriptional and epigenetic programs governing cancer development, progression, and therapeutic vulnerability. We provide mechanistic evidence demonstrating how dietary bioactive compounds and micronu-trients, including polyphenols (curcumin, resveratrol, EGCG), flavonoids, alkaloids such as berberine, omega-3 fatty acids, folate, vitamin D, probiotic metabolites (such as bu-tyrate and propionate), and trace elements (such as selenium, and zinc), modulate on-cogenic and tumor-suppressive lncRNAs. These nutrient-lncRNA interactions influence cancer-relevant pathways controlling proliferation, epithelial-mesenchymal transition, inflammation, oxidative stress, and metabolic rewiring. We further discuss emerging lncRNA signatures that reflect nutritional and metabolic states, their potential utility as biomarkers for individualized dietary interventions, and their integration into liquid biopsy platforms. Leveraging multi-omics datasets and systems biology, we outline AI-driven frameworks to map nutrient-lncRNA regulatory networks and identify tar-getable nodes for cancer chemoprevention. Finally, we address translational challenges, including compound bioavailability, inter-individual variability, and limited clinical validation, and propose future directions for incorporating lncRNA profiling into preci-sion nutrition-guided cancer prevention trials. Together, these insights position lncRNAs at the nexus of diet and cancer biology and establish a foundation for mechanistically informed precision nutrition strategies in cancer chemoprevention.

Abstract: Background: Head and neck squamous cell carcinomas (HNSCC) are aggressive malignancies with high mortality and poor prognosis. Pseudogenes with altered expression during HNSCC progression may serve as potential biomarkers for early detection, prognosis, and therapy selection. Methods: In this report, we analyzed the expression of ANXA2P2 and PA2G4P4 pseudogenes in HNSCC patients using data from The Cancer Genome Atlas. Clinical correlations were assessed through UALCAN and cBioPortal. Functional enrichment was investigated using REACTOME, ESTIMATE, and Gene Set Enrichment Analysis. Statistical analyses were performed with GraphPad Prism 8. Results: Both ANXA2P2 and PA2G4P4 were significantly upregulated in HNSCC compared to normal tissue. Their expression varied based on HPV status and was negatively correlated with overall survival. High pseudogene expression was associated with dysregulated oncogenic pathways, while low expression was linked to distinct immunological profiles. Conclusions: ANXA2P2 and PA2G4P4 exhibit oncogenic properties in HNSCC and hold potential as diagnostic and prognostic biomarkers.

Abstract: Background/Objectives: WHO grade II meningiomas exhibit heterogeneous clinical behavior that cannot be predicted by conventional histology. This study examined the relationship between the tumor immune microenvironment (TIME) and tumor growth kinetics in order to establish a biological basis for more precise risk stratification. Methods: A retrospective cohort of 15 patients was evaluated. Serial preoperative magnetic resonance imaging (MRI) scans were used to calculate the relative growth rate (RGR) and minimize the baseline tumor size. The densities of Iba1-positive macrophages (TAMs) and B7-H3-positive tumor cells were quantified using a deep learning-based image analysis system. Results: Linear correlation analysis showed no significant associations between individual immune components and RGR. However, median-based stratification revealed distinct associations. Tumors with low TAM density or high B7-H3-positive tumor cell density exhibited significantly higher RGR (P = 0.0401). Additionally, a significant inverse relationship was identified between TAM and that of B7-H3-positive tumor cell densities (Spearman’s R = -0.911, P < 0.001). Conclusions: We identified a proliferative "immune-cold" phenotype in WHO grade II meningiomas, which is characterized by low TAM density and high B7-H3-positive tumor cell density. This study extends established molecular frameworks by suggesting that high B7-H3-positive tumor cells proactively contribute to rapid tumor growth. These findings highlight the importance of targeting B7-H3-positive tumor cells when treating malignant meningiomas.

Abstract:

Cadherin-5 (CDH5), also known as vascular endothelial cadherin (VE-cadherin), plays essential roles in endothelial cell adhesion, vascular barrier function, and signaling. CDH5 coordinates endothelial cell–cell junction during vascular remodeling, which is indispensable for both vascular homeostasis and adaptive responses to pathological stimuli. Although anti-CDH5 monoclonal antibodies (mAbs) can be used for individual applications including flow cytometry, western blotting, and immunohistochemistry (IHC), highly sensitive and versatile anti-CDH5 mAbs for all applications remain limited. Here, novel anti-human CDH5 mAbs, designated Ca₅Mabs, were developed using a flow cytometry-based high-throughput screening. Among them, a clone Ca₅Mab-8 (IgG_2a, κ) recognized CDH5-overexpressed Chinese hamster ovary-K1 (CHO/CDH5) cells in flow cytometry. Furthermore, Ca₅Mab-8 also recognized endogenous CDH5-expressing human endothelial cell lines (HUVEC/TERT2 and HDMVEC/TERT164-B) and a cervical cancer cell line (Hela). These reactivities were superior to a commercially available anti-CDH5 mAb (clone BV9). The dissociation constant value of Ca₅Mab-8 for CHO/CDH5 was determined as 6.1 × 10⁻⁹ M. Ca₅Mab-8 can detect endogenous CDH5 in Western blotting. Moreover, Ca₅Mab-8, but not BV9, is available for IHC to detect endothelial cells in formalin-fixed paraffin-embedded tissues. These results indicate that Ca₅Mab-8 is versatile for research and are expected to contribute to clinical applications, such as tumor diagnosis and therapy.