Search Results (9,901)

Albumin-binding agents enhance tumor uptake of radiopharmaceuticals targeting prostate-specific membrane antigens (PSMAs) in radiotherapy. We synthesized PSMA-NARI-56, a molecule with both PSMA targeting activity and albumin-binding moiety, labeled with ¹⁷⁷Lu as the therapeutic agent. The aim of this study was to determine the specific binding of ¹⁷⁷Lu-PSMA-NARI-56 towards PSMA, assess its biodistribution, and evaluate therapeutic effectiveness by tumor-bearing mice. The effect of ¹⁷⁷Lu-PSMA-NARI-56 viability of PSMA-positive cell (LNCaP) was evaluated. Biodistribution and endoradiotherapy studies were utilized to determine the distribution, targeting, and anti-tumor efficacy by tumor-bearing mice identified by ¹¹¹In-PSMA-NARI-56. ¹⁷⁷Lu-PSMA-NARI-56 exhibited a significant impact on the viability of the LNCaP cell. Biodistribution results revealed the maximum tumor uptake of ¹⁷⁷Lu-PSMA-NARI-56 occurring within 24 h, reaching 40.56 ± 10.01%ID/g. In radionuclide therapy, at 58 days post-injection (p.i.), ¹⁷⁷Lu-PSMA-NARI-56 demonstrated superior tumor inhibition (98%) compared to ¹⁷⁷Lu-PSMA-617 (58%), and the mouse survival rate after 90 days of radiotherapy (90%) was also higher than that of ¹⁷⁷Lu-PSMA-617 (30%) in LNCaP tumor-bearing mice. In the PSMA-positive animal model, ¹⁷⁷Lu-PSMA-NARI-56 shows higher potential radiotheranostic and prolonged accumulation (identify by ¹¹¹In-PSMA-NARI-56/nanoSPECT/CT image), offering the potential for improved treatment effectiveness and increased survival rates when compared to ¹⁷⁷Lu-PSMA-617. Full article

Background: RiBi is integral to cell proliferation, and its dysregulation is increasingly recognized as a hallmark of aggressive cancers. We sought to develop and validate a composite “PanRibo-515 score” reflecting RiBi activity across multiple tumor types, assess its prognostic significance, and explore its relationship with immune checkpoint therapy outcomes. Methods: We curated 515 RiBi–associated genes (PanRibo-515) and used a LASSO regression-based strategy on a training dataset (GSE202203) to select the prognostically most relevant subset of 68 genes (OncoRibo-68). Directionality (positive or negative impact on survival) was assigned based on the sign of the LASSO coefficients. We integrated a forward selection approach to identify a refined subset of genes for computing the OncoRibo-68 score. For validation, patients in The Cancer Genome Atlas (TCGA) were stratified into high or low OncoRibo-68 score groups for survival analyses. Additional validation for immunotherapy response was conducted using bioinformatic platforms used for immunotherapy response analysis. Results: A higher OncoRibo-68 score consistently correlated with poorer overall and progression-free survival across multiple cancers. Elevated OncoRibo-68 score was linked to an immunosuppressive tumor microenvironment, but interestingly to increased response to checkpoint inhibitors. Conclusions: Our findings highlight RiBi as an important determinant of tumor aggressiveness and identify the OncoRibo-68 score as a promising biomarker for risk stratification and therapy selection. Future research may evaluate whether targeting RiBi pathways could enhance treatment efficacy, particularly in combination with immunotherapy. Full article

To determine the association between FGFR4 (rs351855 and rs7708357) gene variants, serum levels, and immunohistochemical markers (Ki-67 and p53) in pituitary adenoma (PA), a case-control study was conducted involving 300 subjects divided into two groups: the control group (n = 200) and a group of PA (n = 100). The genotyping of FGFR4 rs351855 and rs7708357 was carried out using the real-time polymerase chain reaction (RT-PCR) method. The serum FGFR4 levels were measured using the ELISA method. Immunohistochemical analysis (Ki-67 and p53) was conducted. Statistical analysis of the data was performed using IBM SPSS Statistics 30.0 software. There were no statistically significant differences after analyzing the genotypes and alleles of FGFR4 rs351855 and rs7708357 in patients with PA and control groups (all p > 0.05). After evaluating the distribution of genotypes and alleles of FGFR4 rs351855 and rs7708357 in micro/macro, invasiveness, activity, and recurrence of PA and the control groups, the analysis showed no statistically significant differences between the groups (p > 0.05). Similarly, no significant differences in FGFR4 levels were observed between PA patients and control group (median (IQR): 3642.41 (1755.08) pg/mL vs. 3126.24 (1334.15) pg/mL, p = 0.121). Immunohistochemistry for Ki-67 revealed a labeling index (LI) of <1% in 25.5% of patients with PA, an LI of 1% in 10.9%, and an LI of >1% in 63.6% of patients. Further analyses showed no statistically significant associations with tumor size, invasiveness, activity, or recurrence. Immunohistochemistry for p53 revealed that macroadenomas had a significantly higher p53 H-score compared to microadenomas (median (IQR): 30.33 (28.68) vs. 18.34 (17.65), p = 0.005). Additionally, a moderate, statistically significant positive correlation between the Ki-67 LI and the p53 expression was found (Spearman’s ρ = 0.443, p = 0.003, n = 43). FGFR4 variants and serum protein levels were not significantly associated with PA risk or tumor features. Conversely, immunohistochemical markers Ki-67 and p53 were more informative, with higher p53 expression in macroadenomas and a moderate positive correlation between Ki-67 and p53, highlighting their potential relevance in tumor growth assessment. Full article

Pancreatic cancer (PC) is an aggressive malignancy with a poor prognosis, requiring innovative approaches to evaluate new therapies. Considering the high activity of unsymmetrical bisacridines (UAs) in PC monolayer cultures, we employed multicellular tumor spheroids (MCTS) to assess whether UAs retain pro-apoptotic activity under more physiologically relevant conditions. Ultra-low attachment plates were used to form spheroids from three PC cell lines (Panc-1, MIA PaCa-2, and AsPC-1) with different genotypes and phenotypes. The effects of UA derivatives (C-2028, C-2045, and C-2053) were evaluated using microscopy and flow cytometry (7-AAD for viability and annexin V-FITC/PI for membrane integrity). UAs altered the morphology of the spheroids and reduced their growth. Notably, Panc-1 spheroids exhibited compromised integrity. The increase in 7-AAD⁺ cells confirmed diminished cell viability, and annexin V-FITC assays showed apoptosis as the dominant death pathway. Interestingly, the exact derivative was most active against a given cell line regardless of culture conditions. These results confirm that UAs maintain anticancer activity in 3D cultures and induce apoptosis, with varying efficacy across different cell lines. This underscores the value of diverse cellular models in compound evaluation and supports UAs as promising candidates for pancreatic cancer therapy. Full article

Cell confluence and number are critical indicators for assessing cellular growth status, contributing to disease diagnosis and the development of targeted therapies. Accurate and efficient cell segmentation is essential for quantifying these indicators. However, current segmentation methodologies still encounter significant challenges in addressing multi-scale heterogeneity, poorly delineated boundaries under limited annotation, and the inherent trade-off between computational efficiency and segmentation accuracy. We propose an innovative network architecture. First, a preprocessing pipeline combining contrast-limited adaptive histogram equalization (CLAHE) and Gaussian blur is introduced to balance noise suppression and local contrast enhancement. Second, a bidirectional feature pyramid network (BiFPN) is incorporated, leveraging cross-scale feature calibration to enhance multi-scale cell recognition. Third, adaptive kernel convolution (AKConv) is developed to capture the heterogeneous spatial distribution of glioma stem cells (GSCs) through dynamic kernel deformation, improving boundary segmentation while reducing model complexity. Finally, a probability density-guided non-maximum suppression (Soft-NMS) algorithm is proposed to alleviate cell under-detection. Experimental results demonstrate that the model achieves 95.7% mAP50 (box) and 95% mAP50 (mask) on the GSCs dataset with an inference speed of 38 frames per second. Moreover, it simultaneously supports dual-modality output for cell confluence assessment and precise counting, providing a reliable automated tool for tumor microenvironment research. Full article

Background/Objectives: Extracellular vesicles (EVs) are involved in cell-to-cell communication and delivery of signaling molecules and represent an interesting approach in targeted therapy. This project focused on EV-mediated facilitation and cell-specific delivery of effector antimiR molecules carried by biologically produced gold nanoparticles (AuNPs). Methods: First, we loaded EVs derived from cancer cells 4T1 with AuNPs-antimiR. The AuNPs were also decorated with or without transferrin (Tf) molecules. We examined parental cell-specific delivery of the AuNPs-Tf-antimiR within monocultures as well as co-cultures in vitro. Subsequently, we used autologous EVs containing AuNPs-Tf-antimiR to target tumor cells in a xenograft tumor model in vivo. Efficacy of the antimir transfer was assessed by qPCR and apoptosis assessment. Results: In vitro, EVs loaded with AuNPs-antimiR were internalized only by the parental cells and the AuNPs-antimiR transfer was successful and effective only in EVs that were decorated with Tf. We achieved effective delivery of the antimiR molecule into cancer cells in vivo, which was proved by specific silencing of the target oncogenic miRNA as well as induction of cancer cells apoptosis. Conclusions: EVs represent an interesting and potent way for targeted cargo delivery and personalized medicine. On the other hand, there are various safety and efficacy challenges that remain to be addressed. Full article

Purpose: The present study aims to evaluate alterations in the peripapillary retinal nerve fiber layer (RNFL) thickness in pediatric patients following surgical resection of childhood-onset craniopharyngioma (CP) and to identify tumor characteristics and other factors influencing these alterations, including changes in the lesion’s location. Design: retrospective clinical cohort study. Methods: A retrospective analysis was conducted on 73 eyes from 38 patients with CP and 64 eyes from 32 age- and sex-matched healthy controls. The mean age of the CP patients was 10.3 ± 4.2 years (range 4–17), while the control group had a mean age of 10.5 ± 3.1 years (range 4–17). Optical coherence tomography (OCT) was used to assess the peripapillary RNFL thickness in the study and control groups. RNFL thickness was analyzed in the superior, inferior, and average sectors, as well as across eight optic nerve sectors. Tumor characteristics were evaluated to determine their correlation with changes in RNFL thickness in individual sectors. Results: Postoperative thickness of peripapillary RNFL in all individual sectors was significantly reduced in the CP group compared to healthy controls. Location, tumor volume, maximum tumor diameter, calcification, ventriculoperitoneal shunt, surgery technique, total resection, presence of Rosenthal fibers, and reoperation due to progression or recurrence correlated with damage to RNFL. Conclusions: CP is associated with significant reductions in RNFL thickness, indicating the tumor’s impact on optic nerve fibers. OCT is a valuable tool for monitoring visual pathway impairment and postoperative outcomes. Correlations between RNFL thickness in individual sectors and clinical parameters may offer valuable insights for diagnosis and monitoring, underlining their potential role in predicting visual outcomes. Regular RNFL evaluation should be integrated into the long-term care of CP patients to optimize visual prognosis and detect progressive or residual damage. Full article

Background/Objectives: Chemotherapy-induced neuropathic pain (CINP) represents a critical challenge in oncology, emerging as a common and debilitating side effect of widely used chemotherapeutic agents, such as paclitaxel (PTX). Current therapeutic interventions and preventive strategies for CINP are largely insufficient, as they fail to address the underlying peripheral nerve damage, highlighting an urgent need for the development of new drugs. This study aimed to investigate the dual-function effects on normal cell protection and tumor suppression of BMX-001, a redox-active manganese metalloporphyrin that has demonstrated antioxidant and anti-inflammatory properties, which offers potential in protecting central nervous system tissues and treating CINP. Methods: This study assessed BMX-001’s different roles in protecting normal cells while acting as a pro-oxidant and pro-inflammatory molecule in cancer cells in vitro. We also evaluated its neuroprotective effect in preclinical PTX-induced CINP models in vivo. Results: Our results showed significant reductions in mechanical and cold allodynia, decreased pro-inflammatory cytokine levels, and restored antioxidant capacity in peripheral nerves and dorsal root ganglia (DRGs) following BMX-001 treatment. Conclusions: Overall, our study highlights the therapeutic potential of BMX-001 to mitigate CINP and enhance anticancer efficiency. Its dual-selective mechanism supports the future clinical investigation of BMX-001 as a novel adjunct to chemotherapeutic regimens. Full article

The aim of this work is to analyse the effectiveness of the medical use of the Cavitron Ultrasonic Surgical Aspirator (CUSA) in microsurgical treatment of Intramedullary Spinal Cord Tumors (IMSCTs), with a focus on the thermo-mechanical effects on neighbouring tissues to assess any potential damage. Indeed, CUSA emerges as an innovative solution, minimally invasive tumor excision technique, enabling controlled and focused operations. This study employs a Finite Element Analysis (FEA) to simulate the vibratory and thermal interactions occurring during CUSA application. A computational model of a vertebral column segment affected by an IMSCT was developed and analysed using ANSYS 2024 software. The simulations examined strain distribution, heat generation, and temperature propagation within the biological tissues. The FEA results demonstrate that the vibratory-induced strain remains highly localised to the application site, and thermal effects, though measurable, do not exceed the critical safety threshold of 46 °C established in the literature. These findings suggest that CUSA can be safely used within defined operational parameters, provided that energy settings and exposure times are carefully managed to mitigate excessive thermal accumulation. These conclusions contribute to the understanding of the thermo-mechanical interactions in ultrasonic tumour resection and aim to assist medical professionals in optimising surgical protocols. Full article

Cancer-related cognitive impairment (CRCI)—encompassing anxiety, depression, and memory deficits—significantly diminishes the quality of life in patients with cancer, yet remains underrecognized in clinical practice. In this study, we investigated the therapeutic potential of tabernanthalog (TBG), a non-hallucinogenic analog of psychedelic compounds, as a novel intervention for CRCI using a Lewis lung carcinoma (3LL) mouse model. Behavioral assessments revealed heightened anxiety-like behavior and memory impairment following 3LL cell transplantation. Biochemical analysis revealed reduced tryptophan levels in both blood and hippocampal tissue, accompanied by the downregulation of serotonergic receptor genes and upregulation of pro-inflammatory cytokine genes in the hippocampus of tumor-bearing mice. Additionally, microglial density and morphological activation were markedly elevated. TBG treatment reversed these behavioral deficits, improving both anxiety-related behavior and memory performance. These effects were associated with the normalization of microglial density and morphology, as well as the restoration of serotonergic receptor and cytokine gene expression. In vitro, TBG partially suppressed neuroinflammatory gene expression in BV-2 microglial cells exposed to conditioned medium from 3LL cells. Collectively, these findings suggest that TBG alleviates CRCI-like symptoms by modulating neuroinflammation and microglial activation. This study highlights TBG as a promising therapeutic candidate for improving cognitive and emotional functioning in patients with cancer. Full article

Background: Autism spectrum disorder (ASD) represents a neurobiological disorder with a high prevalence in the children’s population. The aim of the present review was to assess the current evidence on the use of salivary biomarkers for the early diagnosis of ASD. Materials and methods: A search was conducted on the electronic databases PUBMED/Medline, Google Scholar and Scopus for the retrieval of articles concerning the study topic. Results: A total of 22 studies have been included in the present review considering 21 articles identified from databases and 1 article included using a manual search. A wide range of biomarkers have been proposed for early detection of ASD diseases including nonspecific inflammation markers like interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor α (TNFα), oxidative stress markers like superoxide dismutase and glutathione peroxidase, hormones such as cortisol and oxytocin, various microRNAs including miR-21, miR-132 and miR-137, and exosomes. The techniques used for biomarke detection may vary according to molecule type and concentration. Conclusions: salivary biomarkers could represent a potential useful tool for the primary detection of several systemic diseases including ASD, taking advantage of non-invasiveness and cost-effective capability compared to other biofluid-based diagnostic techniques. Full article

The incidence and mortality of colorectal cancer (CRC) have increased globally. Several therapeutic approaches have been suggested to address this health issue, in addition to classical methods. Propranolol (PRO) is a beta-blocker that was repurposed to treat infantile hemangiomas, and its anti-tumor activity has been reported. This study aimed to investigate the effects of PRO in a panel of CRC cell lines and its potential impact when combined with chemotherapy. The effects of PRO on cell cytotoxicity, cell morphology, colony formation, cell death induction, cell cycle, mitochondrial and intracellular reactive oxygen species (ROS), and migration were measured in all cells. CompuSyn software was utilized to assess the possible synergistic or additive interaction in the combined treatment. The results showed that PRO suppressed cell proliferation, altered cell morphology, inhibited colony formation, induced apoptosis, altered cell cycle and ROS generation, and inhibited the migration of treated cells in a cell-type-specific, time-dependent, and dose-dependent manner compared with the control. HT-29 was the most sensitive cell line to PRO in terms of cytotoxicity, apoptosis, cell cycle arrest, and ROS generation, while SW-480 was the most sensitive in terms of migration inhibition. Moreover, the PRO and capecitabine combination exhibited a synergistic effect and induced mitochondrial apoptosis in metastatic CRC cells. The data suggest that PRO could be a promising adjuvant therapy for primary and advanced CRC. This study identified variations between CRC cell lines in response to PRO, which may be related to their genetic and epigenetic differences. In addition, the findings highlight the potential of combination strategies to improve therapeutic outcomes in metastatic CRC. Full article

Background: This study aimed to evaluate the impact of surgical margin status, tumor size, and adjuvant radiotherapy on local control, overall survival, and postoperative complications in patients undergoing surgery for sacral chordoma. Methods: This retrospective analysis included 18 patients who underwent surgical treatment for primary sacral chordoma between 2002 and 2019. The variables assessed included patient demographics, tumor size and volume, surgical margin status, adjuvant radiotherapy, local recurrence, overall survival, and postoperative complications. Survival analysis was performed using the Kaplan–Meier method, and appropriate parametric or non-parametric tests were used for group comparisons. Results: The cohort’s mean age was 62.6 ± 7.9 years, with a mean follow-up of 8.8 ± 4.1 years and an average tumor volume of 235 cm³. Negative surgical margins (R0) were achieved in 44% of patients. Local recurrence occurred in 50% of R0 cases and 83% of R2 cases. Negative surgical margins (R0) were associated with significantly lower local recurrence rates compared to R1 and R2 resections (Fisher’s exact test, p = 0.043), and showed a trend toward improved overall survival (p = 0.077). Overall survival was significantly lower in patients with tumors measuring ≥ 5 cm (p = 0.031). Adjuvant radiotherapy did not significantly reduce local recurrence (p = 0.245); however, an increase in complication rates was observed, although this association did not reach statistical significance (p = 0.108). Bladder dysfunction was significantly more frequent in patients undergoing S1–S2 resections (p = 0.036). Conclusions: Achieving negative surgical margins improves local control and may prolong survival. Larger tumors (≥5 cm) were associated with worse prognosis. While adjuvant RT may be considered in selected high-risk cases, its efficacy in preventing recurrence is unclear and may increase complication rates. Full article

Hibiscus syriacus L. (HS), native to Eastern and Southern Asia, has been traditionally used in Asian herbal medicine for its anticancer, antimicrobial, and anti-inflammatory properties. Despite these recognized bioactivities, its potential cardioprotective effects, particularly in the setting of heart failure (HF), remain largely unexplored. This study aimed to investigate the effects of HS extracts and its bioactive constituents on angiotensin II (Ang II)-induced cardiac injury using an in vitro model with H9c2 rat cardiomyocytes. Cells exposed to Ang II were pretreated with HS extracts, and assays were performed to assess cell viability, reactive oxygen species (ROS) generation, protein synthesis, and secretion of inflammatory mediators, including tumor necrosis factor-alpha, interleukin 1β (IL-1β), and interleukin 6 (IL-6), as well as chemokine (CCL20) and HF-related biomarkers, such as brain natriuretic peptide (BNP) and endothelin-1. The results demonstrated that HS extracts significantly and dose-dependently attenuated Ang II-induced ROS accumulation and suppressed the secretion of pro-inflammatory cytokines, chemokines, BNP, and endothelin-1. Additionally, HS and its purified components inhibited Ang II-induced protein synthesis, indicating anti-hypertrophic effects. Collectively, these findings highlight the antioxidative, anti-inflammatory, and antihypertrophic properties of HS in the context of Ang II-induced cardiac injury, suggesting that HS may represent a promising adjunctive therapeutic candidate for HF management. Further in vivo studies and mechanistic investigations are warranted to validate its clinical potential. Full article

Feline mammary carcinoma (FMC) exhibits aggressive behavior, with limited treatment options. Given the relevance of the PD-1/PD-L1/PD-L2 axis in human breast cancer immunotherapy, this study assessed PD-1 and its ligands in rare FMC histotypes (n = 48) using immunohistochemistry on tumor cells (TCs), intratumoral lymphocytes (iTILs), and stromal tumor-infiltrating lymphocytes (sTILs). PD-1 was expressed in 13% of TCs, 85% of iTILs, and 94% of sTILs, while PD-L1 was observed in 46% of TCs, 96% of iTILs, and 100% of sTILs. PD-L2 was expressed in 79% of TCs and 100% of both iTILs and sTILs, with PD-L1/PD-L2 co-expression in 42% of TCs. Higher PD-1 IHC scores in TCs were associated with a less aggressive biological behavior; PD-L1 in iTILs was linked to skin ulceration, whereas PD-L2 in TCs was associated with its absence. Our findings highlight the relevance of the PD-1/PD-L1/PD-L2 immune checkpoint in rare FMC subtypes and support further investigation into checkpoint-blockade therapies. Full article