Search Results (3,872)

Breast cancer (BC) requires the evaluation of tumor aggressiveness features to guide treatment decisions. Biopsy-derived prognostic information may differ from surgical histopathology due to tumor heterogeneity. Hybrid PET/MRI can provide additional information for tumor characterization, supporting initial therapy planning and prognosis. In this work, we acquired 157 BC patients using a hybrid PET/MRI scanner. The PET data were combined with ADC and semi-quantitative DCE-MRI metrics to derive “hybrid PET/MRI parameters.” Pathological data such as tumor grade, hormone receptors, proliferation index (Ki67), and surrogate molecular subtype were collected, and we evaluated their associations with hybrid imaging, also comparing with the PET and MRI data analyzed separately. Ki67 showed moderate correlations with PET, ADCmin, and most hybrid parameters. The PET and hybrid data differentiate histopathological factors, while ADCmin differentiates G1 vs. G2 and luminal A vs. luminal B. In the ROC analysis, hybrid SUVmax/ADCmin shows better performance to predict luminal B from luminal A (AUC 0.720, sensitivity 73.1%, specificity 63.2%, PPV 54.3%, NPV 79.7%) than SUVmean alone. Our findings suggest that these novel hybrid PET/MRI parameters may help the characterization of tumor tissue in IDC. However, a multivariate analysis is needed to confirm our preliminary results. Full article

Background: Indoleamine 2,3-dioxygenase (IDO) is an immune checkpoint that has been shown to play a key immunomodulatory role in various solid tumors, including breast cancer (BC). Although increased IDO expression has been previously observed in some BC subtypes, mainly triple-negative BC (TNBC), the clinical relevance of this protein across the entire range of BC and its exact correlations with other immune checkpoints remain to be elucidated. We herein aimed to further investigate the differential expression patterns of IDO and programmed death-ligand 1 (PD-L1) in variable BC subtypes and in distinct compartments of breast cancer tissue, and to explore their potential associations with standard patient- and tumor-related clinicopathological parameters as well as prognosis. Methods: This was a retrospective multi-center cohort study of 150 female patients with BC. The clinicopathological parameters analyzed were retrieved from the medical records of patients while sections from archival formalin-fixed, paraffin-embedded (FFPE) tissue blocks were also obtained for the performance of immunohistochemistry. The expression of IDO and PD-L1 was evaluated separately on tumor cells (IDO/CA, PD-L1/CA), lymphocytes (IDO/L, PD-L1/L) and stromal cells (IDO/S, PD-L1/S) and the results were correlated with the remaining clinical and pathological features of patients, as well as with local recurrence, metastasis and survival. Results: The mean age of patients was 59.5 years (SD = 13.4 years). Positive expression of IDO/CA, IDO/L and IDO/S was found in 6%, 93.3% and 90.7% of tissue samples, respectively, while 4%, 11.2% and 6.7% of tumors were positive for PD-L1/CA, PD-L1/L and PD-L1/S, respectively. A significantly higher rate of positive IDO/CA expression was observed in triple-negative BC (TNBC) patients (p = 0.037). Positive expression of IDO-CA was also significantly associated with positivity for PD-L1/L and PD-L1/S (p = 0.001 and p = 0.015, respectively). Multivariable logistic regression analysis showed independent correlations between IDO/CA and IDO/L and the presence of invasive ductal carcinoma (IDC) (OR = 1.10; p = 0.026) and N1 status (OR = 10.93; p = 0.039), respectively, IDO/S and both N1 (OR = 14.64; p = 0.018) and positive HER2 status (OR = 6.11; p = 0.019), PD-L1/L and high Ki67 (OR = 7.96; p = 0.001) as well as negative ER (OR = 0.08; 0.003) and PR status (OR = 0.09; p = 0.002), PD-L1/S and both NST (no special type) histology (OR = 4.68; p = 0.032) and negative ER status (OR = 0.21; p = 0.044). No statistically significant associations were observed between the expression patterns of the examined biomarkers and recurrence, metastasis or survival. Conclusions: In our study, IDO expression on tumor cells was predominantly observed in TNBC and was found to correlate with PD-L1 expression in the lymphocytic and stromal compartments. Furthermore, expression of PD-L1 among lymphocytes was found to independently correlate with unfavorable clinicopathological parameters, including high proliferation rate and negative hormone receptor status. Full article

Background: Endometrial cancer is the most common gynecologic malignancy in developed countries. Sentinel lymph node (SLN) mapping has emerged as a less invasive alternative to systematic lymphadenectomy and is increasingly incorporated into surgical staging algorithms. Vaginal natural orifice transluminal endoscopic surgery (vNOTES) provides transvaginal access to the retroperitoneum and may facilitate SLN mapping while potentially reducing postoperative morbidity, including lower extremity lymphedema (LEL). Objective: This study aimed to evaluate the feasibility of vNOTES hysterectomy with bilateral salpingo-oophorectomy (BSO) and retroperitoneal SLN mapping and to report early postoperative lymphedema outcomes in patients with newly diagnosed endometrial cancer. Methods: This retrospective cohort study included 113 patients who underwent vNOTES-assisted hysterectomy with BSO and SLN mapping using methylene blue dye at a tertiary referral center between January 2022 and January 2023. Lymphedema was evaluated using the Gynecologic Cancer Lymphedema Questionnaire at 6 and 12 months postoperatively, supported by clinical examination. Descriptive statistical analyses were performed to summarize clinical characteristics and symptom profiles. Results: The mean patient age was 55.0 ± 10.5 years and the mean BMI was 30.94 ± 2.54 kg/m². Endometrioid adenocarcinoma was the most common histological subtype (75.5%), and most tumors were grade 1 (57.1%). SLN mapping was successful in 102 of 113 patients (overall detection rate 90.3%), with bilateral detection in 79.6% and unilateral detection in 10.6% of cases. Limb swelling was reported in 4.1% of patients, while only one patient (1.0%) met the criteria for self-reported mild lymphedema. No clinical signs of inguinal lymphedema were detected. Conclusions: vNOTES hysterectomy combined with retroperitoneal SLN mapping was associated with a low incidence of postoperative lower extremity lymphedema in this single-arm cohort. These findings suggest that vNOTES-assisted SLN mapping may represent a feasible minimally invasive approach for nodal assessment in selected patients with endometrial cancer. Prospective comparative studies are required to confirm these findings and to evaluate long-term oncologic and lymphatic outcomes. Full article

Background: Breast cancer remains a major public health problem, with increasing incidence and persistent survival disparities. In Romania, barriers to early diagnosis and access to multidisciplinary treatment may contribute to poorer outcomes. Methods: We conducted a retrospective single-center cohort study including 118 women diagnosed with and/or treated for breast cancer in our institution between 1 January and 31 December 2020. Patients were followed for 5 years. The primary outcome was overall survival (OS). Clinicopathological characteristics, treatment exposure, pathological response after neoadjuvant therapy, and factors associated with OS were analyzed. Results: The median age at diagnosis was 62 years. Most tumors were located in the upper quadrants, and the most frequent subtype was hormone receptor-positive/HER2-negative breast carcinoma. During follow-up, 26.27% of patients died from disease progression or associated complications. Estimated OS was 88.7% at 1 year and 72.8% at 5 years. Older age at diagnosis and treatment exposure patterns, including the absence of neoadjuvant therapy, were associated with OS. Conclusions: In this single-center retrospective cohort, overall survival was associated with age at diagnosis, tumor characteristics, and treatment patterns. The high proportion of early deaths and the frequent absence of documented surgical treatment in patients who died suggest important challenges related to late presentation, continuity of care, and access to guideline-concordant multidisciplinary treatment in the Romanian setting. Full article

Background and Objectives: Bladder cancer is one of the most common malignancies of the urinary tract and poses a significant clinical challenge due to its biological heterogeneity and high rates of recurrence and progression. Urothelial carcinoma represents the predominant histological subtype, ranging from non-muscle-invasive disease with relatively favorable outcomes to aggressive muscle-invasive and metastatic forms associated with poor prognosis. Accurate diagnosis, staging, prognostic stratification, and assessment of treatment response are therefore essential for optimal patient management. The objective of this review is to summarize and critically evaluate the current evidence on the role of positron emission tomography/computed tomography (PET/CT) in bladder cancer, with particular emphasis on [¹⁸F]FDG PET/CT and non-FDG radiotracers. Materials and Methods: A narrative review of the available literature was performed, focusing on clinical studies, review articles, and guideline documents addressing the use of PET/CT in bladder cancer. The literature search included articles published between 2000 and 2025, while earlier landmark studies were selectively included if considered historically important for understanding the development of PET/CT imaging in bladder cancer. The initial search yielded over 500 records; after screening titles and abstracts, more than 100 articles were selected for full-text evaluation. The analyzed evidence encompasses the clinical applications of [¹⁸F]FDG PET/CT and alternative radiotracers, including choline-, acetate-, methionine-, and sodium fluoride-based tracers, and fibroblast activation protein inhibitors (FAPI), across different stages of disease and clinical settings. Results: Conventional imaging modalities, such as computed tomography and magnetic resonance imaging, provide important anatomical information but remain limited in the evaluation of lymph node involvement, early metastatic disease, treatment response, and disease recurrence. Despite limitations related to physiological urinary excretion, [¹⁸F]FDG PET/CT has demonstrated clinical value in selected scenarios, particularly for staging, prognostic assessment, detection of recurrence, and response evaluation. To overcome FDG-related constraints, several non-FDG radiotracers have been investigated. Among these, FAPI PET/CT has emerged as a promising modality due to its ability to target the tumor stroma, potentially improving lesion detectability and tumor-to-background contrast. Conclusions: This review summarizes and critically evaluates current evidence on the role of PET/CT in bladder cancer, with a focus on [¹⁸F]FDG PET/CT and non-FDG radiotracers. The discussed studies highlight their applications in primary diagnosis, staging, prognostic assessment, detection of recurrence, and evaluation of treatment response, as well as their respective advantages and limitations. Furthermore, potential future directions for PET/CT imaging in clinical practice are outlined, emphasizing the need for further research to clarify the optimal use of established and emerging radiotracers. 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

Background/Objectives: Malignant salivary gland tumors (MSGTs) are rare, biologically heterogeneous neoplasms in which histopathologic diagnosis and classification are challenging and subject to interobserver variability. Artificial intelligence (AI) approaches using radiologic, histopathologic, and molecular data, including radiomics, deep learning, and biomarker-based models, have been proposed as adjunctive diagnostic tools. This systematic review aimed to identify and critically appraise AI/ML models across radiologic, histopathologic, and molecular domains for distinct diagnostic tasks in MSGTs, and to integrate their diagnostic roles through a functional meta-synthesis. Methods: We conducted a PRISMA 2020-compliant systematic review. Embase, PubMed/MEDLINE, and Scopus were searched from inception to February 2026. Eligible studies developed or validated AI/ML diagnostic or classification models in human salivary gland tumor cohorts and reported extractable performance metrics. Results: From 1265 records, eight studies (1922 participants) met the inclusion criteria, spanning CT/MRI radiomics or deep learning (n = 4), whole-slide histopathology deep learning (n = 3), and DNA methylation-based classification (n = 1). External validation was reported in two CT-based benign–malignant discrimination studies, with AUCs of 0.890 (95% CI 0.844–0.937) and 0.745 (95% CI 0.699–0.791). Heterogeneity in model construction, outcome definitions, and validation strategies precluded meta-analysis. Risk of bias was frequently high in QUADAS-2/PROBAST assessments, driven by retrospective sampling, limited blinding, and analysis-related concerns, while calibration and utility were rarely assessed. Conclusions: AI/ML models for MSGTs demonstrate promising diagnostic performance, particularly for preoperative benign–malignant discrimination, but the current evidence base is limited by heterogeneity, predominantly internal validation, and high risk of bias. The functional meta-synthesis identified three convergent diagnostic domains: malignancy discrimination, histopathologic subtype classification, and molecular/epigenetic taxonomy refinement. Full article

Atypical teratoid rhabdoid tumor (AT/RT) is a rare, highly aggressive embryonal central nervous system malignancy occurring predominately in infants and toddlers. Spinal AT/RT (spAT/RT) cases are even more limited, and as a result, little is known regarding prognostic factors and optimal treatment regimens. Molecularly, AT/RT is divided into three groups: AT/RT-SHH, AT/RT-TYR and AT/RT-MYC. spAT/RT is predominantly of the MYC subtype. Additionally, a third of patients with AT/RT have a germline Rhabdoid Tumor Predisposition Syndrome (RTPS) that increases the likelihood of developing additional rhabdoid tumors, including renal rhabdoid tumors. Due to the rarity of these tumors, there is a lack of consensus on treatment strategies to be employed. This review paper details the published literature on spAT/RT, with particular emphasis on the recent advances in understanding the biology of these aggressive tumors and currently available therapeutic options, and highlights the challenges associated with the management of this extremely rare condition. 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

Background/Objectives: High-grade serous ovarian cancer (HGSOC) represents the most aggressive subtype of epithelial ovarian cancer and is frequently diagnosed at advanced stages. Increasing evidence suggests that systemic inflammation plays an important role in tumor progression and clinical outcomes. This study aimed to evaluate the association between preoperative systemic inflammatory indices and tumor burden, perioperative outcomes, and recurrence risk in patients with HGSOC undergoing primary debulking surgery. Methods: We conducted a retrospective study including 125 patients with histopathologically confirmed HGSOC who underwent primary debulking surgery between January 2020 and December 2025. Preoperative hematological parameters obtained within 24 h before surgery were used to calculate inflammatory indices including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), and aggregate index of systemic inflammation (AISI). Associations between inflammatory markers, clinicopathological characteristics, perioperative outcomes, and recurrence were analyzed using non-parametric tests and logistic regression models. Results: The mean patient age was 53.66 ± 9.14 years, and most patients presented with advanced disease (FIGO III–IV: 70.4%). Patients with T3 tumors showed significantly higher monocyte (0.66 vs. 0.50 × 10⁹/L, p = 0.003), neutrophil (5.43 vs. 4.99 × 10⁹/L, p = 0.042), and platelet counts (325 vs. 280 × 10⁹/L, p = 0.006) and lower lymphocyte counts (1.79 vs. 1.96 × 10⁹/L, p = 0.009). Composite inflammatory indices were also increased in advanced disease, including PLR (177 vs. 153, p = 0.009), AISI (492 vs. 341, p = 0.002), and SIRI (1.65 vs. 1.18, p = 0.018). Patients requiring postoperative blood transfusion had higher neutrophil counts (7.65 vs. 4.97 × 10⁹/L, p < 0.001) and elevated SIRI (2.56 vs. 1.55, p < 0.001). Patients with recurrence had significantly higher platelet counts (339 vs. 293 × 10⁹/L, p = 0.001) and SII values (2849 vs. 2586, p = 0.012). In multivariate analysis, SII remained independently associated with recurrence (OR 1.022 per 100-unit increase; 95% CI 1.002–1.043; p = 0.033) together with advanced FIGO stages (OR 2.863; 95% CI 1.011–8.104; p = 0.048). Conclusions: Preoperative systemic inflammatory markers are significantly associated with tumor burden, surgical outcomes, and recurrence risk in HGSOC. An elevated SII appears to be an independent predictor of recurrence and may represent a practical biomarker for improving preoperative risk stratification and postoperative surveillance. Full article

The impact of anesthetic technique on long-term oncologic outcomes remains controversial. While early observational data suggested that regional anesthesia might reduce cancer recurrence, large randomized trials have failed to demonstrate consistent survival benefits. This apparent contradiction may not reflect biological neutrality, but rather a mismatch between trial design and the inflammatory biology of the perioperative period. Surgical resection provokes an acute and intense inflammatory surge characterized by sympathetic activation, cytokine release, neutrophil extracellular trap formation, endothelial activation, and transient suppression of cellular immunity. During this perioperative inflammatory window, circulating tumor cells encounter a biologically permissive microenvironment that may facilitate immune evasion, adhesion, and early metastatic niche establishment. The magnitude of this inflammatory response varies across patients and may represent a critical, yet under-recognized, determinant of tumor–host dynamics. Anesthetic and analgesic strategies influence this inflammatory cascade. By attenuating nociceptive signaling and sympathetic activation, regional anesthesia may modulate perioperative immune and immunometabolic pathways. However, it should not be framed as an anti-cancer therapy per se, but rather as a potential regulator of the transient inflammatory milieu that shapes early oncologic biology. We propose that prior neutral trials may reflect methodological misalignment, including heterogeneous tumor populations, absence of inflammatory stratification, and reliance on distant survival endpoints without mechanistic correlates. Future investigations should integrate perioperative immune phenotyping, inflammatory biomarkers, and tumor subtype stratification to determine whether modulation of acute surgical inflammation meaningfully alters early tumor–host interactions. Reconceptualizing the perioperative period as a biologically active inflammatory interface may refine the anesthesiologist’s role within perioperative oncology and open new avenues for precision-based perioperative modulation. Full article

Background and Objectives: Immunohistochemistry (IHC) is a keystone in gastric cancer (GC) management, allowing treatment customization, including for advanced or metastatic diseases. This review aims to evaluate the critical role of IHC markers, analyzing their efficiency in molecular subclassification and prediction of response to gastric cancer-targeted therapies, while also describing state-of-the-art IHC techniques and perspectives. Results: The major challenges for the GC management were structured in two main sections, as follows: (i) the current paradigm of gastric neoplasia diagnosis, which includes subsections related to the methodological and morphological foundations, the epidemiological dynamics, and risk factors, as well as differential diagnosis of poorly differentiated tumors; and (ii) the progress in 3,3′-diaminobenzidine (DAB) application and advanced reagents in gastric cancer immunohistochemistry. Discussion: Considering the role of IHC and DAB, the following topics were successively addressed in seven sections: GC key biomarkers, such as human epidermal growth factor receptor 2 (HER2), programmed death-ligand 1 (PD-L1), and DNA replication mismatch repair (MMR) system, allow direct correlation between tissue morphology and protein expression; intestinal and gastrointestinal differentiation markers; emerging and aggressive histological subtypes; epithelial–mesenchymal transition, E-cadherin, and the process of tumor budding; implementation of innovative procedures in gastric cancer immunohistochemistry; and automation, quality control, and sustainability in the pathology laboratory. Perspectives: The main directions were focused on the integration of artificial intelligence (AI) algorithms for digital quantification of the IHC signal and also on the expansion of panels to new targets, such as Claudin 18.2 (CLDN 18.2), which redefines treatment approaches in advanced stages. Conclusions: Although faced with technical and biological limitations, immunohistochemistry remains indispensable in modern gastric oncology. The evolution towards digital pathology and the refinement of scoring criteria will transform IHC from a complementary test into a visual tool that is essential for personalizing oncological treatment. Full article

Biological heterogeneity among different breast cancer (BC) subtypes results in markedly varying clinical outcomes. Identification and analysis of key gene biomarkers that are differentially regulated during radiation therapy (RT) may pose multiple clinical challenges for BC treatment. The purpose of the study is to identify and analyze the expression of key gene biomarkers and their networks that are differentially regulated after hypofractionated RT. Patients with BC (cT0-T2, N0, M0) were treated with hypofractionated whole breast RT 25 Gy in five fractions, 4 to 8 weeks before breast conservation surgery (BCS). Biopsy (pre-RT; n = 5) and surgical (post-RT; n = 14 or 15) BC tumor samples were used for NanoString targeted sequencing. We identified 165 and 244 differentially expressed genes (DEGs; p < 0.05) in BC tumor samples from BC patients post-RT using the nCounter BC360 and IO360 panels, respectively. Gene networks and pathway analysis revealed that RT increases the gene signature of tumor inflammation (TIS), cytotoxicity, and apoptosis, while downregulating the gene signatures of tumor cell proliferation, differentiation, and cell adhesion, and increases the claudin-low gene score. RT-induced mammary stemness and enhanced infiltration of stroma, mast, and macrophage cells in the BC tumor microenvironment (TME). Further, the nCounter IO360 (immuno-oncology) panel analysis validated the findings of BC360 and demonstrated that RT increased the myeloid inflammation signature and chemokine expression, modulated B, T, NK, and DC cell activities, and enhanced residual cancer burden (RCB) in BC tumors, thus creating an immunosuppressive TME. Collectively, RT sensitized BC tumors by increasing the gene signature of TIS, cytotoxicity, apoptosis, and mammary stemness. RT facilitated an immunosuppressive environment and increased RCB, suggesting that the therapeutic potential of RT is highly individualized for each patient based on their unique tumor biology, genetic makeup, and TME. Full article

Endoscopic sinus surgery (ESS) is commonly performed to treat chronic rhinosinusitis and selected sinonasal tumors, yet postoperative complications such as neo-osteogenesis and restenosis remain frequent, largely due to impaired mucosal regeneration after extensive epithelial and bony tissue loss. Successful nasal epithelial repair requires a microenvironment that preserves cell viability, phenotype, and barrier integrity. Conventional culture substrates often lack physiological relevance or rely on animal-derived components, limiting translational applicability. In this study, we evaluated nanofibrillar cellulose (NFC) hydrogel (GrowDex^®) as a xeno-free scaffold for primary human nasal epithelial cells (NECs). NECs isolated from healthy donor tissue were characterized by immunofluorescence and qPCR for basal, goblet, and ciliated cell markers. Cells embedded in NFC were assessed for viability, cytotoxicity, epithelial morphology, and barrier function. Transepithelial electrical resistance (TEER) and FITC-dextran permeability assays were used to quantify barrier integrity and compared with collagen- and polylysine-based controls. NECs cultured in NFC maintained high viability, stable epithelial morphology, and preserved subtype-specific marker expression without detectable cytotoxicity. NFC-supported cultures demonstrated enhanced barrier formation, indicated by higher TEER values and reduced paracellular permeability relative to controls, and sustained structural integrity during extended culture. These findings identify NFC hydrogel as a biocompatible, non-animal scaffold that supports functional human nasal epithelium regeneration and may contribute to advanced tissue engineering strategies for craniofacial bone repair. Full article

Background and Objectives: Mycosis fungoides (MF) is the predominant subtype of cutaneous T-cell lymphoma, whereas large plaque parapsoriasis (LPP) closely resembles early-stage MF, making differential diagnosis challenging. Immune markers, such as CD47, CD163, and B7-H3, play crucial roles in tumor immune evasion and macrophage polarization. However, their expression profiles and potential diagnostic or prognostic implications in early-stage MF and LPP remain poorly defined. Therefore, this study aimed to evaluate the expression of CD47, CD163, and B7-H3 in early-stage MF and LPP and analyze their associations with clinicopathological characteristics and patient outcomes. Materials and Methods: This retrospective study evaluated the immunohistochemical expression of CD47, CD163, and B7-H3 in 46 patients with early-stage mycosis fungoides (MF) and 46 patients with large plaque parapsoriasis (LPP). Expression levels were assessed using an immunoreactivity scoring system and analyzed for their associations with clinical parameters and disease-free survival (DFS). The study included patients diagnosed and followed at Sivas Cumhuriyet University between 1 March 2015 and 31 March 2025. Results: High CD47 expression was detected in 72.7% of MF patients, high B7-H3 expression in 45.7%, and high CD163 expression in 46.7% compared with LPP patients (p < 0.001). These markers showed positive correlations, and elevated expression, especially of B7-H3 and CD163, was associated with shorter disease-free survival in univariate analysis. Conclusions: The higher expression of CD47, CD163, and B7-H3 in early-stage MF compared with LPP suggests that these markers may contribute to the differential diagnosis and could represent potential therapeutic targets; however, their independent prognostic value requires confirmation in larger studies. Full article