Search Results (3,245)

Gallium-68 is a widely used positron-emitting radionuclide in nuclear medicine, traditionally obtained from ⁶⁸Ge/⁶⁸Ga generators. However, increasing clinical demand has driven interest in alternative production methods, such as medical cyclotrons equipped with solid targets. This study evaluates the functional equivalence of gallium-68 chloride obtained from cyclotron solid target and formulated to be equivalent to the eluate from a germanium-gallium generator, aiming to determine whether this production method can serve as a reliable alternative for PET radiopharmaceutical applications. Preparations of [⁶⁸Ga]Ga-PSMA-11 and [⁶⁸Ga]Ga-DOTATOC, labeled with cyclotron-derived gallium-68 chloride, were subjected to quality control analysis using radio thin layer chromatography and radio high performance liquid chromatography. Subsequently, biodistribution studies were performed in mouse oncological models of expression of PSMA antigen and SSTR receptor to compare uptake of preparations produced with generator and cyclotron-derived isotopes. All tested formulations met the required radiochemical purity specifications. Moreover, tumor accumulation of the radiolabeled compounds was comparable regardless of the isotope source. The results support the conclusion that gallium-68 produced via cyclotron is functionally equivalent to that obtained from a generator, demonstrating its potential for interchangeable use in clinical and research radiopharmaceutical applications. Full article

Background/Objectives: Human endogenous retroviruses (ERVs) are genomic sequences integrated into the human genome from ancestral exogenous retroviruses and are epigenetically silenced under normal conditions. Growing evidence has shown that they can be reactivated in human diseases such as cancers and autoimmune diseases. However, their clinical implications in colon cancer are yet to be explored. Methods: RNA-seq data were downloaded from RNA Atlas and TCGA for cell lines and tissue samples, respectively. After alignment, ERV expression was quantified against comprehensively compiled ERVs (3220). ERV expression profiles were compared between sequencing protocols, cancer and normal cells, and matched tumor and normal tissue pairs. Unsupervised clustering was used to identify ERV-defined tumor subtypes and their associations with clinical and other molecular features. ERV association with disease-specific survival (DSS) was performed using the Cox regression model. Results: PolyA and total RNA protocols were comparable in ERV expression detection. Cancer cells had significantly increased ERV expression and reactivation. Upregulated ERVs were significantly enriched in viral protein interactions with cytokine and cytokine receptors. ERV expression-defined tumor classes were significantly associated with tumor mutation burden and immuno-phenotypes such as antigen processing and presenting machinery and tumor immune infiltration score. Survival analysis identified 152 ERVs to be independently associated with DSS. Conclusions: ERV abnormal expression is common in colon cancer. The ERV-defined subtypes are associated with tumor immunity, and some ERVs are independently associated with patient outcomes. Full article

Mannan oligosaccharide (MOS), a prebiotic derived from yeast cell walls, has been shown to enhance growth performance and health status in various aquatic species. As an exogenous antigen adjuvant, MOS modulates T-cell-mediated immune responses, thereby improving immune function and suppressing excessive inflammatory reactions. This study aimed to evaluate the effects of dietary MOS supplementation on growth performance, serum biochemical parameters, muscle composition, digestive enzyme activity, antioxidant and immune status, and the mTOR signaling pathway in juvenile GIFT tilapia (Oreochromis niloticus). Juveniles (initial body weight: 16.17 ± 1.32 g) were randomly assigned to six treatment groups (three replicate tanks per group) and fed diets supplemented with MOS at 0, 0.2%, 0.4%, 0.6%, 0.8%, and 1% (equivalent to 0, 2, 4, 6, 8, and 10 g/kg of diet, respectively) for 60 days. Compared with the control group, fish fed MOS-supplemented diets exhibited significantly higher (p < 0.05) weight gain rates, specific growth rates, and protein efficiency ratios, along with a significantly lower (p < 0.05) feed conversion ratio. Serum albumin, high-density lipoprotein, and lysozyme levels were significantly increased (p < 0.05), whereas triglycerides, low-density lipoprotein, aspartate aminotransferase, and alanine aminotransferase levels were significantly decreased (p < 0.05). In the liver, head kidney, and spleen, the expression of pro-inflammatory genes (tumor necrosis factor α, interleukin 1β, interleukin 6, interleukin 8, and interferon γ) was significantly downregulated (p < 0.05), while the expression of antioxidant and protective genes (superoxide dismutase, catalase, glutathione peroxidase, glutathione S-transferase, nuclear factor erythroid 2-related factor 2, lysozyme, alkaline phosphatase, interleukin-10, transforming growth factor β, and heat shock protein 70) as well as mTOR signaling pathway-related genes (mammalian target of rapamycin, akt protein kinase B, phosphatidylinositol 3 kinase, and ribosomal protein S6 kinase polypeptide 1) was significantly upregulated (p < 0.05). Overall, MOS positively affects tilapia’s growth, health, and immunity, with 0.60% identified as the optimal dietary level based on growth performance. Full article

Glycosylation, the enzymatic addition of glycans to proteins and lipids, is a critical post-translational modification that influences protein folding, stability, trafficking, immune modulation, and cell signaling. The vast structural diversity of glycans arising from differences in monosaccharide composition, branching, and terminal modifications such as sialylation, fucosylation, and sulfation underpins their functional specificity and regulatory capacity. This review provides a comprehensive overview of glycan biosynthesis, with a focus on N-glycans, O-glycans, glycosaminoglycans (GAGs), and glycolipids. It explores their essential roles in maintaining cellular homeostasis, development, and immune surveillance. In health, glycans mediate cell–cell communication, protein interactions, and immune responses. In disease, however, aberrant glycosylation is increasingly recognized as a hallmark of numerous pathological conditions, including cancer, neurodegenerative disorders, autoimmune diseases, and a wide range of infectious diseases. Glycomic alterations contribute to tumor progression, immune evasion, therapy resistance, neuroinflammation, and synaptic dysfunction. Tumor-associated carbohydrate antigens (TACAs) and disease-specific glycoforms present novel opportunities for biomarker discovery and therapeutic targeting. Moreover, glycan-mediated host–pathogen interactions are central to microbial adhesion, immune escape, and virulence. This review highlights current advances in glycomics technologies, including mass spectrometry, lectin microarrays, and glycoengineering, which have enabled the high-resolution profiling of the glycome. It also highlights the emerging potential of single-cell glycomics and multi-omics integration in precision medicine. Understanding glycome and its dynamic regulation is essential for uncovering the molecular mechanisms of disease and translating glycomic insights into innovative diagnostic and therapeutic strategies. Full article

This study investigates two cases of stage IVb de novo multi-metastatic nasopharyngeal carcinoma (NPC) that responded to immunotherapy but resulted in different outcomes. Case 1 involved a multi-metastatic NPC patient (T4N3M1) with extensive bone and lymphatic metastases and severely impaired physical condition (ECOG PS 2) who showed significant tumor reduction after one cycle of immunotherapy combined with non-platinum chemotherapy, with no radiation exposure. Due to financial difficulties, the patient received intermittent immunotherapy plus chemotherapy and survived 28 months with a good quality of life. Case 2 describes a multi-metastatic NPC patient (T3N2M1) with multi-organ (bone and liver) metastases and good performance status (ECOG PS 0) who underwent standard chemotherapy, immunotherapy, and radiotherapy but experienced rapid progression and died after 21 months. Immunotherapy combined with chemotherapy remains the standard for multi-metastatic NPC patients. Patients responsive to induction chemotherapy gain survival benefits from subsequent radiotherapy. However, the advantages and disadvantages of radiotherapy for immunotherapy-sensitive multi-metastatic NPC patients are still unclear. Radiotherapy (RT) can enhance local control and promote tumor antigen release, thereby complementing immunotherapy; yet it can also damage immune cells, leading to exhaustion and resistance. Therefore, balancing RT and chemotherapy is vital for optimizing immune synergy and preventing immune exhaustion. Full article

Intercellular mitochondrial transfer in the tumor microenvironment (TME) is a paradigm-shifting process that redefines cancer–T cell crosstalk. This review explores its dual nature as both a tumor immune evasion strategy and a promising therapeutic avenue. Crucially, oxidative stress acts as a key regulator, inducing tunneling nanotube (TNT) formation to facilitate this organelle exchange. Tumors exploit this by transferring dysfunctional, reactive oxygen species (ROS) generating mitochondria to T cells to induce senescence while simultaneously hijacking healthy mitochondria from T cells to empower their own metabolism. This directional exchange, quantified by computational tools like mitochondrial-enabled reconstruction of cellular interactions (MERCI), is linked to poor clinical outcomes. Transfer occurs via TNTs, extracellular vesicles, and direct contact. Conversely, the therapeutic transfer of healthy mitochondria from sources like mesenchymal stromal cells can revitalize exhausted T cells, improving chimeric antigen receptor T (CAR-T) cell efficacy. Clinical translation is guided by emerging biomarkers, including circulating mitochondrial DNA (mtDNA), mitochondrial haplogroups, and the tumor mitochondrial transfer (TMT) score. Harnessing this biological axis for next-generation immunotherapies requires overcoming challenges in transfer efficiency and standardization to effectively modulate the tumor redox landscape and immune response. Full article

Background: Melanoma is one of the most aggressive types of skin cancer. Its diagnosis appears to be challenging due to morphological similarities to benign melanocytic lesions. Even though histopathological evaluation is the diagnostic gold standard, immunohistochemistry (IHC) proves to be useful in challenging cases. Preferentially Expressed Antigen in Melanoma (PRAME) has emerged as a promising diagnostic, prognostic, and therapeutic marker in melanoma. Methods: This review critically examines the role of PRAME across clinical domains. It presents an evaluation of PRAME’s diagnostic utility in differentiating melanomas from benign nevi, its prognostic significance across melanoma subtypes, and therapeutic applications in emerging immunotherapy strategies. An extensive analysis of the current literature was conducted, with a focus on PRAME expression patterns in melanocytic lesions and various malignancies, along with its integration into IHC protocols and investigational therapies. Results: PRAME demonstrates high specificity and sensitivity in distinguishing melanoma from benign melanocytic proliferations, particularly in challenging subtypes such as acral, mucosal, and spitzoid lesions. Its overexpression correlates with poor prognosis in numerous malignancies. Therapeutically, PRAME’s HLA class I presentation enables T-cell-based targeting. Early-phase trials show promising results using PRAME-directed TCR therapies and bispecific ImmTAC agents. However, immune evasion mechanisms (i.e., heterogeneous antigen expression, immune suppression in the tumor microenvironment, and HLA downregulation) pose significant challenges to therapy. Conclusions: PRAME is a valuable biomarker for melanoma diagnosis and a promising target for immunotherapy. Its selective expression in malignancies supports its clinical utility in diagnostic precision, prognostic assessment, and precision oncology. Ongoing research aimed at overcoming immunological barriers will be essential for optimizing PRAME-directed therapies and establishing their place in the personalized management of melanoma. Full article

Chimeric antigen receptor (CAR) cell therapy, encompassing CAR T, CAR NK, and CAR macrophage cells, demonstrates high efficacy in tumor treatment, conferring durable and effective responses, notably in hematologic malignancies. However, challenges persist in the manufacture of CAR cells, and treatment is associated with serious adverse events, notably cytokine release syndrome (CRS), a potentially life-threatening complication. Owing to the inherent properties of exosomes, CAR cell-derived exosomes offer distinct advantages in cancer therapeutics. CAR cells-derived exosomes retain the inherent tumor-killing function of the parent cells while also exhibiting key practical advantages, including wide availability, safety, and ease of storage and transport. Furthermore, CAR cell-derived exosomes can be combined with other tumor therapies; this combinatorial approach significantly enhances efficacy while reducing side effects. To accelerate the clinical translation of CAR cell-derived exosomes in tumor therapy, this paper reviews their biogenesis, engineering strategies, antitumor mechanisms and clinical evidence, including case studies of combination therapies with other antitumor modalities. Full article

Background/Objectives: Colorectal cancer (CRC) frequently metastasizes to the peritoneum, significantly worsening patient prognosis. While serum tumor markers such as carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA 19-9) are routinely measured, their diagnostic or prognostic role in peritoneal fluid remains unclear. This study aimed to assess the relationship between CEA and CA 19-9 levels in both serum and peritoneal fluid, and the clinical stage of CRC, particularly focusing on the presence of peritoneal metastases and positive cytology. Methods: We retrospectively analyzed data from 89 patients with histologically confirmed CRC who underwent surgery between 2020 and 2023. All patients had preoperative assessment of CEA and CA 19-9 levels in serum and peritoneal fluid, along with cytological examination of peritoneal fluid samples. Patients were categorized based on the presence or absence of macroscopic peritoneal metastases and cytology results. Results: Elevated levels of CEA and CA 19-9 in peritoneal fluid were significantly associated with the presence of peritoneal metastases. A positive cytological finding also correlated with higher marker concentrations. Conclusions: CEA and CA 19-9 levels in peritoneal fluid strongly correlate with peritoneal dissemination in CRC. These markers may serve as additional predictive factors, aiding in early detection of peritoneal spread and improved risk stratification. Their assessment may be useful in guiding intraoperative and postoperative decision-making. Full article

Glioblastoma multiforme (GBM) is one of the most aggressive cancers, with limited treatment options due to its highly immunosuppressive microenvironment and resistance to conventional therapies. γδ T cells, known for their potent antitumor activity and ability to recognize tumor antigens independently of HLA molecules, have emerged as a promising therapeutic strategy. This review explores the role of γδ T cells in glioblastoma, focusing on their functional plasticity, cytotoxic mechanisms, and interactions with components of the tumor microenvironment. We examine the factors that influence γδ T cell polarization toward pro- or anti-tumor phenotypes and analyze preclinical findings that support their application in GBM treatment. Furthermore, we discuss potential combinatory approaches—including immune checkpoint inhibitors, cytokine stimulation, and adoptive cell transfer techniques—to enhance the therapeutic effectiveness and persistence of γδ T cells. Understanding the dynamics between GBM and γδ T cells may pave the way for innovative immunotherapeutic strategies aimed at overcoming immune evasion and improving clinical outcomes. Full article

In Brazil, the annual scorpion sting cases surpass those of other neglected tropical diseases, highlighting a significant public health issue. The severity of scorpion envenomation relates to the venom’s rapid action, complex composition, species identification challenges, and limited antivenom availability. This work aimed to characterize the venom of Tityus confluens through proteomic, enzymatic, and biological analyses while also assessing its reactivity to anti-scorpion antivenom. The electrophoretic analysis revealed seven protein bands, with the most prominent bands at 30, 15, and 10 kDa. The C18-RP-HPLC analysis isolated sixteen primary fractions. The proteomic analysis identified various toxins, including potassium channel toxins, sodium channel toxins, and antimicrobial peptides, as well as other proteins such as hypotensin and metalloproteinases. Antigenic components were identified in the T. confluens venom, which displayed dose-dependent but time-independent amylolytic activity. The ATPase activity significantly increased with 1–10 μg of venom. No cytotoxic effects were observed on carcinoma or non-tumoral cell lines. The T. confluens venom features a complex protein composition rich in toxins that target ion channels and enzymes. It exhibits active enzymatic and antigenic properties, and displays low cytotoxicity. This is the first proteomic research on the composition of T. confluens venom and may provide valuable insights into understanding the clinical manifestations of scorpion stings. Full article

Background: Hemoglobin (Hb) has been identified to be an independent prognostic marker for oncological outcomes in several malignancies. However, the impact of Hb levels before radical prostatectomy (RP) in localized prostate cancer remains unclear. Methods: Preoperative Hb levels were retrospectively collected from patients, who underwent RP from 2016 to 2022. Hb levels were analyzed as continuous and binary variables. For binary analysis, the cohort was divided into high-Hb (≥150 g/L) and low-Hb (<150 g/L) groups using the median as a cutoff. We used Spearman rank correlation to assess possible associations between Hb and continuous variables and logistic regression for Hb and binary variables. To assess the impact of preoperative Hb on recurrence-free survival (RFS), adjuvant treatment free survival (TFS), and metastasis-free survival (MFS), univariate and multivariate Cox regression analyses were performed. Results: A total of 567 patients were included in the analysis. Higher Hb levels, both when analyzed as a continuous variable and when divided in high and low groups, were inversely correlated with age (p < 0.001) and the International Society of Urological Pathology (ISUP) grade (p = 0.005 or p = 0.028, respectively). Patients in the high-Hb group showed a decreased risk of extraprostatic disease (≥pT3) (odds ratio [OR] 0.71, 95%-CI: 0.50–0.99, p = 0.047). In univariate cox regression analysis, high-Hb patients had a significantly longer RFS compared to the low-Hb group (hazard ratio [HR] 0.64, 95%-CI: 0.44–0.92, p = 0.015). When adjusting for age, ISUP grade, positive surgical margin, prostate specific antigen, nodal status, and ≥pT3, this effect was no longer statistically significant (HR 0.76, 95%-CI 0.56–1.22, p = 0.178). Hb was not a significant prognostic factor for TFS or MFS. Conclusions: In this large cohort, lower preoperative Hb values were associated with a more aggressive tumor grading and shorter RFS. However, we were unable to identify Hb as an independent predictor of oncological survival outcomes. Full article

Introduction: Serum biomarkers such as CA-125 and HE4, along with the ROMA score, (which integrates both markers) are widely used to distinguish between benign and malignant ovarian tumors. In ovarian cancer, chronic exposure to tumor-associated antigens (TAAs), such as CA-125 and HE4, can lead to T cell exhaustion and senescence, thereby facilitating immune evasion. This study aimed to evaluate exhausted and senescent T cells in the peripheral blood of patients with benign or malignant ovarian tumors, and compare these findings to those of healthy donors, and assess their correlation with the ROMA score. Methods: The expression of senescent and exhaustion markers was evaluated on peripheral CD4⁺ T cells from patients with benign and malignant ovarian tumors, as well as healthy donors. Multicolor flow cytometry was performed to evaluate the expression of CTLA-4, PD-1, Tim3, CD28, CD57, and CD27. Results: PD1⁺Tim3⁺CD4⁺ expression was significantly higher in the malignant group compared to both the benign group (p = 0.05) and healthy donors (p = 0.015). A positive and significant correlation was observed between ROMA and PD-1⁺Tim3⁺ T cells (r = 0.44, p = 0.0006). The confusion matrix demonstrated good classification accuracy, and in the ROC analysis, the combination of ROMA and PD-1⁺Tim3⁺ yielded the highest Youden Index (0.75) and superior specificity (88.8%) compared to ROMA alone, albeit with a slight reduction in sensitivity (86.9% vs. 91.3%). A nomogram integrating ROMA and PD-1⁺Tim3⁺ exhibited strong predictive performance, with a concordance index (C-index) of 0.91. Conclusion: The combination of the ROMA score with the expression of PD-1⁺ and Tim-3⁺ in CD4⁺ T cells creates a simple yet highly effective model to differentiate between benign and malignant ovarian tumors. Full article

(1) Background: The gold standard, prostate-specific antigen (PSA) screening lacks the sensitivity and specificity required for confident, early prostate-cancer detection. MicroRNAs (miRNAs) are small, highly stable, non-coding RNAs whose expression changes reproducibly in malignancy and therefore offer promise as minimally invasive biomarkers. Although prostate cancer biopsies are the gold standard for prostate cancer diagnosis, limitations in the field continue to persist. Since circulating fluids can also be a source of miRNA biomarkers, we investigated the overlap between miRNAs enriched in prostate cancer tissue and those isolated from the plasma of patients with prostate cancer. (2) Methods: We synthesized the published literature (PubMed, Google Scholar, ResearchGate, 2005–April 2025) and re-analyzed three Gene Expression Omnibus (GEO) datasets (GSE54516, GSE21032—tissue; GSE206793—plasma) to identify miRNAs consistently dysregulated in prostate cancer tissue and circulation. (3) Results: Of the 318 screened full-text articles, 24 met the inclusion criteria. From the GEO reanalysis (false-discovery-rate < 0.05, |log₂FC| ≥ 1), 219 and 326 miRNAs were differentially expressed in tissue, whereas 12 were altered in plasma. Two miRNAs—miR-449b and miR-455-3p—were common in both compartments, highlighting their translational potential as liquid biopsy surrogates of tumor biology. (4) Conclusions: We summarize functional evidence for leading tumor-suppressive (e.g., miR-205, miR-23b, miR-455-3p) and oncogenic (e.g., miR-21, miR-182, miR-449b) candidates, discuss their intersection with the androgen-receptor, TGF-β, WNT/β-catenin, and PI3K-AKT signaling, and outline outstanding requirements for the clinical qualification of miRNA panels in prostate cancer. Full article

High-risk prostate cancer (PC) accounts for 50–75% of 10-year relapse after primary treatment. Routine clinicopathological parameters for PC patient stratification have proven insufficient to inform clinical decisions in this setting. Tumor genomic profiling allowed overcoming the limits of diagnostic accuracy in the field of PC, integrated with radiomic features, automated platforms, evaluation of patient-related factors (age, performance status, comorbidity) and tumor-related factors (risk class, volume, T stage). In this scenario, the use of biomarkers to guide decision-making in localized, high-risk PC is evolving actively and rapidly. Additional tests for prostate-specific antigen have demonstrated superior sensitivity and specificity for detecting clinically significant PC, as well as commercially available genomic classifiers improving the risk prediction of disease recurrence/progression/metastasis, in combination with common clinical variables. This narrative review aimed to summarize the state of the art on the utility and evolution of old and emerging biomarkers in the diagnosis and prognosis of localized, high-risk PC, and the potential for their application in clinical practice. We focused on the theoretical molecular foundation of prostate carcinogenesis and explored the impact of genomic profiling, next-generation sequencing, and artificial intelligence in the extrapolation of customized features able to predict disease aggressiveness and possibly drive personalized therapeutic decisions. Full article