Search Results (3,137)

Biosensors based on electrolyte-gated organic field-effect transistors (EGOFETs) have attracted considerable attention due to their advantages, including low cost, inherent signal amplification, and low-voltage operation. A critical step influencing sensing performance is the integration of specific receptors onto the device surface. Among various strategies, the covalent immobilization of biorecognition elements onto gold surfaces via thiol chemistry is one of the most widely used approaches. In this study, we report the optimization of a mixed self-assembled monolayer (SAM) composed of 11-mercaptoundecanoic acid (11-MUA) and 3-mercaptopropionic acid (3-MPA) for label-free detection of human IgG using EGOFETs. The quality of the SAM was systematically modulated by varying the total concentration from 10 to 400 mM and characterized using X-ray Photoelectron Spectroscopy (XPS), Electrochemical Impedance Spectroscopy (EIS), Cyclic Voltammetry (CV), and Atomic Force Microscopy (AFM). The results revealed that a concentration of 50 mM yielded a densely packed and well-ordered monolayer. After covalent immobilization of anti-IgG antibodies via 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride/N-hydroxysuccinimide (EDC/NHS) chemistry and subsequent blocking with ethanolamine and bovine serum albumin (BSA), the functionalized gate electrodes were integrated into poly(3-hexylthiophene) (P3HT)-based EGOFETs. Electrical measurements demonstrated that EGOFET biosensors functionalized with the 50 mM SAM achieved optimal sensing performance. The devices exhibited a highly linear response (R² = 0.998) over a wide concentration range from 1 fM to 10 nM, with a LOD of 2.82 fM, and showed excellent selectivity against non-target immunoglobulins A and M (IgA and IgM). This SAM concentration optimization strategy provides a versatile approach for engineering high-performance EGOFET biosensors, with potential applicability to a broad range of disease biomarkers. Full article

Background: Mycoplasma pneumoniae (MP) is a major cause of respiratory tract infections in children and adolescents. Currently, there is no licensed vaccine, underscoring the urgent need for the development of safe and effective vaccines. Objective: The aim of this study is to develop a recombinant subunit vaccine candidate incorporating three antigens: the P1 protein, the P40/90 complex, and a detoxified mutant of community-acquired respiratory distress syndrome toxin. The protective efficacy of this vaccine candidate was also evaluated. Methods: Target genes were codon-optimized for expression in E. coli, and the recombinant proteins were successfully expressed and purified. The low-toxicity CARDS toxin mutant was screened based on TNF-α secretion levels in stimulated RAW264.7 cells. A three-component vaccine composed of P1, P40/90, and the mutant CARDS toxin was formulated and adjuvanted with either Al(OH)₃ alone or in combination with CpG. Mice were immunized, and immunogenicity was assessed by measuring antigen-specific IgG antibody titers. Protective efficacy was evaluated following challenge by analyzing lung histopathology, bacterial load, and inflammatory cytokine levels. Results: Seven high-purity recombinant proteins were successfully produced, including P1, the P40/90 complex, wild-type CARDS toxin, and four CARDS toxin mutants (E132A, E132Q, H36A, R10A). The E132A mutant was selected due to its significantly reduced toxicity while retaining immunogenicity. The three-component vaccine effectively elicited antibody responses against each of the included antigens. After three immunizations, IgG antibody titers in all groups reached approximately 10⁴. Immunized mice showed markedly reduced pulmonary pathology scores (control group: 2 or 2.67; immunized groups: 1.67, 1.33, and 0) and significantly decreased bacterial loads in lung tissue (control: 30.11 ± 10.40 cp/μL; immunized groups: 20.72 ± 4.37 cp/μL and 8.51 ± 8.32 cp/μL). Furthermore, the group receiving the alum + CpG adjuvant exhibited approximately a 10-fold higher antibody response compared with the alum-only group, indicating enhanced protective efficacy. Conclusions: The three-component candidate vaccine, MPtriV, adjuvanted with Al(OH)₃ + CpG, demonstrates promising immunogenicity, safety, and protective efficacy against Mycoplasma pneumoniae infection, providing a viable strategy and experimental foundation for the development of MP subunit vaccines. Full article

Molecular subtype–guided therapy for breast cancer (BC) remains limited in a subset of patients by suboptimal efficacy, acquired resistance, and the presence of “undruggable” targets. Proteolysis-targeting chimeras (PROTACs) represent a targeted protein degradation (TPD) strategy that differs fundamentally from conventional occupancy-driven inhibition. By inducing ubiquitination of a protein of interest and subsequent proteasomal degradation, PROTACs can directly reduce pathogenic protein abundance and potentially abrogate non-catalytic or scaffolding functions, thereby enabling more durable pathway suppression in selected resistance contexts. This review comprehensively summarizes the mechanisms of action, key molecular design elements, and the developmental landscape of PROTACs, and maps target selection and research progress across BC molecular subtypes. In hormone receptor–positive/HER2-negative BC, clinical translation is most advanced for estrogen receptor alpha-directed PROTACs; Phase III evidence indicates biomarker-dependent efficacy, with clearer benefit signals in resistant subgroups such as estrogen receptor 1 mutations, suggesting that the net clinical benefit of TPD is more likely to be realized through precision stratification. In contrast, in solid-tumor settings, including human epidermal growth factor receptor 2 (HER2)-positive BC and triple-negative breast cancer, PROTAC translation is more frequently constrained by an “exposure–selectivity–therapeutic window” trade-off driven by physicochemical liabilities, insufficient tumor penetration, and broad target expression. Accordingly, engineering strategies—such as antibody/aptamer-mediated targeted delivery, stimulus-responsive prodrugs, nanocarriers, and local administration—are emerging as decisive approaches to enable safe and effective clinical implementation. Looking forward, further progress of PROTACs in BC will depend on expanding the spectrum of E3 ubiquitin ligases and recruitment modalities, establishing predictable and dynamically monitorable biomarker systems, optimizing rational combination/sequencing regimens with exposure- and schedule-guided dosing, and advancing scalable manufacturing and quality control capabilities, thereby translating mechanistic advantages of TPD into verifiable precision-therapy applications. Full article

Antibody–drug conjugates (ADCs) represent a paradigm shift in precision oncology, ingeniously coupling the targeting capability of monoclonal antibodies with the lethal potency of cytotoxic payloads to selectively eradicate tumor cells. While ADCs have demonstrated transformative efficacy across a spectrum of malignancies, the emergence of intrinsic and acquired resistance remains a formidable obstacle, frequently culminating in treatment failure and disease progression. The landscape of ADC resistance is highly complex, governed by a diverse array of molecular mechanisms. These range from alterations in antigen dynamics—such as downregulation or impaired trafficking—to intracellular adaptations, including the upregulation of multi-drug resistance efflux pumps, enhanced DNA damage repair capacity, and the blockade of apoptotic cell death. Moreover, tumor cells often exploit compensatory signaling networks to bypass therapeutic inhibition. Consequently, elucidating the intricate signaling cascades that drive these resistance phenotypes is critical for clinical advancement. This review comprehensively examines the pivotal signaling pathways underpinning ADC resistance and evaluates novel therapeutic strategies designed to circumvent these molecular barriers, aiming to optimize patient outcomes. Full article

Background/Objectives: While intravitreal administration allows for increased ocular exposure to anti-TNF-α monoclonal antibodies, there is still a need for developing delivery systems able to prolong ocular drug exposure and alleviate patient compliance and safety concerns because of repeated injections. Therefore, the objective of this work was to guide the design of sustained-release formulations of anti-TNF-α monoclonal antibodies for intravitreal administration through a model-based strategy in non-infectious uveitis in the preclinical setting. Methods: Using an in-house-developed anterior uveitis disease model in rats, an intravenous reference dose reducing free TNF-α by 90% at the biophase was established. Intravitreal administrations of sustained-release formulations every 24 weeks were then simulated for adalimumab, golimumab and infliximab to evaluate TNF-α kinetics in the anterior chamber of the eye at different release rates. The selected sustained-release formulation was further evaluated for possible formulation issues causing device emptying before the next administration. Results: Intravitreal administration of sustained-release formulations releasing adalimumab, golimumab or infliximab at 1.802, 0.979 and 1.442 μg/week, respectively, met the predefined criteria of ≥90% reduction in free TNF-α at the biophase. TNF-α levels in aqueous humour were anticipated to be the most sensitive to detect possible formulation issues. Formulation emptying 10, 4 or 8 weeks for adalimumab, golimumab and infliximab, respectively, before next administration triggered TNF-α reaching pathological levels at week 24 post-dose. Conclusions: This work underscores the potential of new approach methodologies in the preclinical drug development of sustained-release formulations for intravitreal administration in ocular inflammatory disorders with less animal testing and without compromising the accuracy of model-informed predictions for human translation. Full article

Background: Egg proteins are among the most common triggers of allergic reactions. This study aimed to evaluate whether changes in the protein source in hen diets may influence the immunoreactivity of eggs and recognize the ELISA limits in egg allergen detection. Methods: This study used eggs from laying hens fed various feeds (including soy and lupin). Determinations of selected allergens were performed using the immunoenzymatic ELISA method. Results: Studies have shown that including legumes in hens’ diets reduces egg immunoreactivity. The highest detected reactivity using a commercial test for the immunoreactivity of egg albumen was twice as high in whites from hens fed the control diet, and this result was most likely due to the Gal d 1 and Gal d 3 detection. Still, the use of this diet reduced the lysozyme (Gal d 4) content in the egg white by approximately 10%. The applied method did not allow for Gal d 5 determination in the tested eggs. The results of the immunoreactivity of the studied eggs with anti-soy and anti-lupine antibodies were outside the limits of detection. Conclusions: The obtained results confirm that the studied allergen content in eggs can be modified by nutritional factors. Full article

Colorectal cancer (CRC) remains a leading cause of cancer morbidity and mortality worldwide, with nearly one quarter of patients presenting with metastatic disease at diagnosis. The epidermal growth factor receptor (EGFR) plays a central role in CRC pathogenesis through activation of downstream RAS/RAF/MAPK and PI3K/AKT/mTOR signaling pathways, and has become a major therapeutic target. Anti-EGFR monoclonal antibodies, cetuximab and panitumumab, have demonstrated survival benefit in selected patients, particularly those with left-sided, RAS wild-type tumors. However, primary and acquired resistance limit their efficacy, underscoring the need for predictive biomarkers and novel strategies. This review synthesizes current knowledge of EGFR biology, therapeutic integration, and biomarker development, including RAS and BRAF mutations, MSI status, HER2 amplification, EGFR ligands (AREG/EREG), consensus molecular subtypes, and liquid biopsy applications. We also discuss mechanisms of resistance such as pathway reactivation, receptor mutations, and epithelial-to-mesenchymal transition, alongside emerging approaches, including combination regimens, ctDNA-guided rechallenge, and genotype-specific inhibitors. Collectively, these insights highlight the evolving landscape of precision oncology in CRC and the importance of molecular stratification to optimize EGFR-targeted therapy and overcome resistance. Full article

Targeted therapies are reshaping oncology by enabling treatment selection based on actionable molecular alterations, improving precision, and reducing unnecessary toxicity. This review provides an up-to-date overview of current targeted treatment modalities and the medicinal chemistry principles that support their discovery and optimization. We synthesize evidence on small-molecule and biologic strategies spanning receptor and non-receptor kinases and their major signaling axes (PI3K-AKT-mTOR and RAS-RAF-MEK-ERK), apoptosis regulation (BCL-2 family), DNA repair via poly(ADP-ribose) polymerase (PARP) inhibition, and epigenetic or metabolic targets including histone deacetylases (HDACs), bromodomain and extra-terminal proteins (BET), and mutant isocitrate dehydrogenases (IDH1/2). Across these areas, we summarize recurrent resistance mechanisms and the rationale for combination or sequential approaches. Biologic targeted therapy is discussed in parallel, including immune checkpoint blockade, antibody–drug conjugates, bispecific antibodies (BsAb), and cell therapies such as chimeric antigen receptor T cells, with emphasis on biomarker-guided patient stratification. Finally, we outline emerging directions beyond canonical nodes, including modulation of the p53-MDM2/MDM4 axis, ferroptosis control through AIFM2/FSP1, and innate immune pathways such as CD47-SIRPa and the stimulator of interferon genes (STING). Overall, the field is shifting from single-target inhibition toward integrated strategies that combine precise molecular targeting with an understanding of signaling network dynamics, resistance evolution, and therapeutic vulnerabilities. Full article

Antibody–drug conjugates (ADCs) have become an important class of targeted anticancer therapeutics by integrating the tumor selectivity of monoclonal antibodies with the potent cytotoxicity of small-molecule payloads through rational linker design. This review summarizes the structural fundamentals of ADCs, including antibodies, linkers, and payloads, and describes their coordinated mechanism of action. We trace the evolutionary trajectory of ADCs across three generations, highlighting key breakthroughs, limitations, and representative agents for each era. Furthermore, we elaborate on cleavage mechanisms of linkers (cleavable and non-cleavable). We also categorize and discuss cytotoxic payloads, covering traditional microtubule-disrupting agents, DNA-damaging agents, and novel mechanism-based payloads, along with their modification strategies and preclinical/clinical performance. Finally, we discuss representative and clinically influential ADC designs, with emphasis on the relationships among antibody, linker, and payload. Full article

Background: This study aimed to assess the prevalence of PD-L1 protein expression in dermatofibrosarcoma protuberans (DFSP) to provide insights into the potential use of immune checkpoint inhibitors. Methods: We retrospectively analyzed formalin-fixed, paraffin-embedded primary DFSP specimens (n = 17). Diagnoses were confirmed by two senior dermatopathologists according to guideline criteria, including diffuse CD34 positivity and storiform spindle cell morphology. All cases represented conventional DFSP without fibrosarcomatous transformation. PD-L1 immunohistochemistry was carried out using a rabbit monoclonal antibody (ab205921, clone 28-8; Abcam). Only membranous staining in viable tumor cells was scored as a tumor proportion score (TPS), where >1% was considered positive. Any cytoplasmic staining without convincing membranous accentuation was not scored. PD-L1 staining in tumor-infiltrating immune cells was recorded separately. Five pleomorphic dermal sarcomas served as positive controls. Results: The median age was 62 years (IQR 55–74); 12 patients were men and 5 were women. The primary sites were trunk (59%), upper extremity (35%), and lower extremity (6%); immunosuppression was present in 18%. By FNCLCC, 82% of tumors were G1 and 18% were G2; no G3 tumors were identified. All DFSPs were PD-L1-negative in DFSP cells (TPS ≤ 1%) and in tumor-infiltrating lymphocytess. Among controls, 3/5 pleomorphic dermal sarcomas were PD-L1-positive with the expected membranous pattern and variable intensity. Conclusions: PD-L1 expression was absent in this cohort of conventional, predominantly low-grade DFSP, suggesting that classic DFSP is generally not an ideal candidate for PD-1/PD-L1-directed checkpoint blockade. These conclusions should not be extrapolated to fibrosarcomatous DFSP or metastatic disease, where PD-L1 expression has been reported. Selective PD-L1 testing may still be warranted in clinically aggressive scenarios (e.g., fibrosarcomatous transformation, unresectable recurrence, or metastasis). Full article

Background: Crimean-Congo hemorrhagic fever (CCHF) is a severe tick-borne viral disease with a high fatality rate, and no licensed vaccines are currently available. The nucleoprotein (NP) of the Crimean-Congo hemorrhagic fever virus (CCHFV) plays a critical role in viral replication and immune recognition, making it a promising target for vaccine development. This study aimed to design and evaluate a multiepitope recombinant DNA vaccine targeting the NP of CCHFV. Methods: Cytotoxic T lymphocyte (CTL) epitopes from the NP were predicted via immunoinformatics approaches and systematically assessed for antigenicity, allergenicity, toxicity, hydrophobicity, and global population coverage. The selected epitopes were incorporated into four DNA vaccine constructs driven by a cytomegalovirus promoter, adjuvanted with human β-defensin 3 (hBD3), and fused to the reporter protein mRuby3. The constructs were evaluated in vitro using a fluorescent reporter system designed to provide a readout of TCR signaling upon the co-culture of T lymphocytes with differentiated monocytic cells expressing antigens. In vivo immunogenicity and protective efficacy were assessed in BALB/c (exploratory pilot) and IFNAR^−/− mice, a highly susceptible model for viral infection. Cytokine responses were measured to assess immunogenicity. Results: In vitro assays showed predominantly antigen-independent T-cell activation, suggesting that nonspecific stimulation inherent to the reporter co-culture system likely obscured the detection of antigen-specific TCR signaling. In vivo analyses in BALB/c mice revealed that the constructs elicited only modest systemic cytokine profiles while CCHFV-specific IgG and IFN-γ secretion remained undetectable, indicating that antigen-specific T-cell and antibody responses were limited. In the IFNAR^−/− challenge model, several peptide groups achieved significant 2–3 log reductions in tissue viral RNA and infectious titers (p < 0.05 vs. sham). However, the observed viral modulations were insufficient to reach the protective threshold and did not translate to a survival benefit (0%). Conclusion: Despite a rational in silico foundation, the multiepitope DNA vaccine constructs demonstrated limitations in inducing potent, antigen-specific immunity across both mouse models. The lack of antigen-specific responses indicates limitations in epitope selection, construct design, and delivery strategies, requiring optimization of next-generation epitope-based vaccines. These findings highlight the complexity of translating computational epitope predictions into functional vaccines, and provide benchmark data as a framework to guide future optimizations. Full article

Antibody–drug conjugates (ADCs) are reshaping the therapeutic approach to advanced gastrointestinal cancers by integrating tumor-specific monoclonal antibodies with potent cytotoxic payloads to improve targeted tumor cell destruction while minimizing systemic exposure. Compared to traditional chemotherapy, trastuzumab deruxtecan has significantly improved objective response rates and overall survival in HER2-positive gastric and gastroesophageal junction tumors after trastuzumab-based therapy. This supports its role as an important second-line or later treatment option. The ongoing advancement of ADCs targeting CLDN18.2, TROP2, and CEACAM5 indicates that this therapeutic category will continue to expand across gastrointestinal neoplasms. Nonetheless, these advancements are accompanied by a specific and clinically significant toxicity profile. Hematologic suppression, gastrointestinal side effects, hepatotoxicity, and notably interstitial lung disease (ILD) are essential consequences that may need inpatient assessment and care. Interstitial lung disease (ILD), although uncommon, may be severe or lethal if not identified immediately and treated swiftly with medication cessation and corticosteroids. In hospitalized patients, distinguishing ADC-related toxicity from infection or disease progression is often difficult owing to overlapping clinical manifestations, requiring meticulous evaluation and interdisciplinary cooperation. As ADCs are integrated into earlier treatment lines and across a broader patient population, hospital systems must evolve to ensure prompt identification, consistent management protocols, and efficient collaboration between oncology and inpatient teams. This study analyzes the mechanisms, clinical effectiveness, and safety profile of ADCs in gastrointestinal oncology, pointing out the importance of institutional preparedness to safely incorporate these medicines into standard clinical practice. These features also align ADC therapy with personalized medicine by emphasizing biomarker-guided patient selection and individualized toxicity monitoring. Full article

Pseudomonas aeruginosa causes severe healthcare-associated infections, yet no vaccine has been licenced. To circumvent the antigenic variability of classical surface antigens, we evaluated LolB—an essential outer-membrane lipoprotein whose periplasmic orientation favours T-cell-dominant mechanisms with potential antibody access via outer-membrane vesicles (OMVs) or bacteriolysis. An integrative in silico pipeline combined multi-strain conservation (20 isolates), epitope discovery (B- and T-cell), safety filters, physicochemical profiling, de novo/refined 3D modelling, molecular dynamics (MD), and docking to TLR4/MD-2. LolB was highly conserved (95–100% identity) under strong purifying selection (dN/dS = 0.15). A conformational B-cell hotspot centred on Q72 mapped to a solvent-accessible flexible loop. Two class II epitopes—LAAQNSPLT and FLGSAAAVS—showed predicted high affinity (IC₅₀ < 10 nM), non-toxicity, and broad coverage, with the pooled set achieving 98.6% global HLA coverage in silico. The final 119-aa construct (N-terminal hBD-3 adjuvant; GPGPG linkers) was compact and tractable (MW = 12.7 kDa; instability index < 40; near-neutral GRAVY) and scored higher for antigenicity than native LolB (VaxiJen 0.82 vs. 0.41). MD supported thermal stability up to 350 K, linker RMSF < 1.5 Å, and a stable 18.2 ± 2.8 Å interdomain spacing. Docking predicted a 1420 Ų interface and ΔG = −10.2 kcal·mol⁻¹ (Kd = 28 nM) with reproducible polar contacts, suggesting productive TLR4/MD-2 engagement. A conservative R42A/K variant is proposed to temper IFN-γ bias. This work therefore suggests an essentiality-anchored LolB-derived multi-epitope construct as a computational vaccine candidate against multidrug-resistant P. aaeruginosa and defines specific experimentally testable hypotheses for future in vitro/in vivo assessment. Essentiality-anchored epitope selection plus adjuvant-surface engineering yielded a structurally coherent, immunologically rational LolB-derived multi-epitope vaccine warranting experimental validation. Full article

Background/Objectives: Rheumatoid arthritis (RA) is a chronic, inflammatory, autoimmune disease that primarily affects the joints. Current treatments aim to relieve pain and limit joint damage; however, many are associated with significant side effects or high costs. Neutrophils play a critical role in RA development and progression by driving synovial inflammation and tissue damage, yet no approved therapies directly target neutrophil-mediated pathogenic mechanisms. Cannabinoids have demonstrated anti-inflammatory potential. Although cannabinoids have been studied in RA, the direct modulation of neutrophil-driven mechanisms by purified CBG has not been systematically addressed. To harness the cannabinoid potential, we investigated the effects of the purified cannabinoid Cannabigerol (CBG) on neutrophil-mediated immune responses in RA. Methods: We assessed the effects of CBG on human blood isolated neutrophil cytokine secretion, signal transduction and migration as ex vivo models. In addition, collagen antibody-induced arthritis (CAIA) was applied in C57BL/6 wt mice, and immune-cell recruitment and cytokine secretion were examined after CBG treatment. Results: Ex vivo experiments demonstrated that CBG hampered the secretion of pro-inflammatory cytokines from human neutrophils in a dose-dependent manner (TNF-α and IL-6 by 68% and 72%, respectively). Furthermore, CBG downregulated inflammatory signal transduction, such as P38-MAPK, ERK1/2 and Akt phosphorylationpost neutrophil activation by 41%, 54% and 78%, respectively. Importantly, 60% of the CBG downregulation of IL-6 was consistent with the CB2 receptor axis in a selective way. In addition, CBG attenuated neutrophil migration toward IL-8 by 67%. To further evaluate CBG therapeutic capacity, we used CAIA as an in vivo model. CBG treatment resulted in improving mice arthritis clinical scores and body weight in comparison to RA-diseased mice. Moreover, CBG reduced leukocyte recruitment to the inflamed joints by 48%, primarily through the inhibition of neutrophil and monocyte cells to 27% and 49%, respectively. Additionally, CBG showed its anti-inflammatory effect by decreasing inflammatory cytokines like IL-6 and IL-1β by 98% and 60% in the blood. Also, CBG reduced MCP-1 and IL-1β cytokines in the joints by 22% and 38%, respectively. Conclusions: These results show that CBG has anti-inflammatory capacity and therapeutic potential in regulating neutrophil-mediated immunity in RA. These findings are preclinical and require further validation before therapeutic positioning. Full article

Background: Paraneoplastic limbic encephalitis (PLE) with anti-Ma2 antibodies is a rare immune-mediated disorder associated with testicular cancer, particularly in young males. While neurological manifestations are well documented, hypothalamic–pituitary dysfunctions remain underreported. We present a case of anti-Ma2 PLE associated with testicular cancer together with a systematic review of PLE associated with testicular cancer, selectively restricted to anti-Ma2 positive cases and focusing on hypothalamic–endocrine involvement. Case presentation: We describe a 21-year-old male diagnosed with anti-Ma2 PLE and intratubular germ cell neoplasia of the right testis. He underwent orchifunicolectomy and immunosuppressive therapy with neurological improvement. Four years later, he developed new-onset temporal seizures, decreased libido, and a polyuria–polydipsia syndrome. Dynamic endocrine testing, including a water deprivation test and copeptin measurement, supported a diagnosis of partial central diabetes insipidus (CDI). Methods: A systematic literature review was performed in accordance with PRISMA guidelines. PubMed was searched using predefined keywords without time restriction. Studies reporting PLE associated with testicular tumors in humans with confirmed anti-Ma2 antibody positivity were included. Results: Eleven studies were included, reporting a total of 38 patients with anti-Ma2-associated PLE and testicular cancer. Hypothalamic or diencephalic involvement was described in 16 patients (42.0%), while endocrine manifestations were explicitly reported in four cases. Only two previous reports mentioned CDI, without detailed diagnostic evaluation. Conclusions: This study highlights the importance of recognizing hypothalamic-endocrine manifestations in PLE. In patients presenting with polydipsia and polyuria, CDI should be carefully differentiated from primary polydipsia using dynamic testing. Hypothalamic involvement may emerge years after tumor treatment, warranting long-term endocrine surveillance. Full article