Search Results (6,166)

Osteosarcoma (OS) is the most common primary bone malignancy in children and adolescents, which is also considered an aggressive disease due to its rapid growth rate, ability to metastasize early, and complex and heterogeneous tumor microenvironment (TME). Although we are developing improved surgical and chemotherapeutic approaches, the presence of metastatic or recurrent disease is still detrimental to the patient’s outcome. Major advances in understanding the molecular mechanisms of OS are needed to substantially improve outcomes for patients being treated for OS. This review integrates new data on the molecular biology, pathophysiology, and immune landscape of OS, as well as introducing salient areas of tumorigenesis underpinning these findings, such as chromothripsis; kataegis; cancer stem cell dynamics; and updated genetic, epigenetic, and glycosylation modifiers. In addition, we review promising biomarkers, diagnostic platforms, and treatments, including immunotherapy, targeted small molecule inhibitors, and nanomedicine. Using genomic techniques, we have defined OS for its significant genomic instability due to TP53 and RB1 mutations, chromosomal rearrangements, and aberrant glycosylation. The TME is also characterized as immunosuppressive and populated by tumor-associated macrophages, myeloid-derived suppressor cells, and regulatory T cells, ultimately inhibiting immune checkpoint inhibitors. Emerging fields such as glycomics and epigenetics, as well as stem cell biology, have defined promising biomarkers and targets. Preclinical studies have identified that glycan-directed CAR therapies could be possible, as well as metabolic inhibitors and 3D tumor models, which presented some preclinical success and could allow for tumoral specificity and enhanced efficacy. OS is a biologically and clinically complex disease; however, advances in exploring the molecular and immunologic landscape of OS present new opportunities in biomarkers and the development of new treatment options with adjunctive care. Successful treatments in the future will require personalized, multi-targeted approaches to account for tumor heterogeneity and immune evasion. This will help us turn the corner in providing improved outcomes for patients with this resilient malignancy. Full article

Prostate cancer (PC) remains a leading cause of malignancy in men worldwide, with current diagnostic methods such as prostate-specific antigen (PSA) testing and tissue biopsies facing limitations in specificity, invasiveness, and ability to capture tumor heterogeneity. Liquid biopsy, especially analysis of circulating tumor DNA (ctDNA), has emerged as a transformative tool for non-invasive detection, real-time monitoring, and treatment selection for PC. This review examines the role of ctDNA in both localized and metastatic PCs, focusing on its utility in early detection, risk stratification, therapy selection, and post-treatment monitoring. In localized PC, ctDNA-based biomarkers, including ctDNA fraction, methylation patterns, fragmentation profiles, and mutations, demonstrate promise in improving diagnostic accuracy and predicting disease recurrence. For metastatic PC, ctDNA analysis provides insights into tumor burden, genomic alterations, and resistance mechanisms, enabling immediate assessment of treatment response and guiding therapeutic decisions. Despite challenges such as the low ctDNA abundance in early-stage disease and the need for standardized protocols, advances in sequencing technologies and multimodal approaches enhance the clinical applicability of ctDNA. Integrating ctDNA with imaging and traditional biomarkers offers a pathway to precision oncology, ultimately improving outcomes. This review underscores the potential of ctDNA to redefine PC management while addressing current limitations and future directions for research and clinical implementation. Full article

Ventricular tachycardia (VT) remains a major cause of morbidity and mortality in patients with structural heart disease. While catheter ablation has become a cornerstone in VT management, recurrence rates remain substantial due to limitations in electroanatomic mapping (EAM), particularly in cases of deep or heterogeneous arrhythmogenic substrates. Cardiac imaging, especially when multimodal and integrated with mapping systems, has emerged as a critical adjunct to enhance procedural efficacy, safety, and individualized strategy. This comprehensive review explores the evolving role of various imaging modalities, including echocardiography, cardiac magnetic resonance (CMR), computed tomography (CT), positron emission tomography (PET), and intracardiac echocardiography (ICE), in the preprocedural and intraprocedural phases of VT ablation. We highlight their respective strengths in substrate identification, anatomical delineation, and real-time guidance. While limitations persist, including costs, availability, artifacts in device carriers, and lack of standardization, future advances are likely to redefine procedural workflows. Full article

The fungal pathogen Puccinia striiformis f. sp. tritici, which causes yellow rust disease, poses a significant economic threat to wheat production not only in Uzbekistan but also globally, leading to substantial reductions in grain yield. This study aimed to develop yellow rust-resistance wheat lines by introgressing Yr10 and Yr15 genes into high-yielding cultivar Grom using the marker-assisted backcrossing (MABC) method. Grom was crossed with donor genotypes Yr10/6*Avocet S and Yr15/6*Avocet S, resulting in the development of F₁ generations. In the following years, the F₁ hybrids were advanced to the BC₂F₁ and BC₂F₂ generations using the MABC approach. Foreground and background selection using microsatellite markers (Xpsp3000 and Barc008) were employed to identify homozygous Yr10- and Yr15-containing genotypes. The resulting BC₂F₂ lines, designated as Grom-Yr10 and Grom-Yr15, retained key agronomic traits of the recurrent parent cv. Grom, such as spike length (13.0–11.9 cm) and spike weight (3.23–2.92 g). Under artificial infection conditions, the selected lines showed complete resistance to yellow rust (infection type 0). The most promising BC₂F₂ plants were subsequently advanced to homozygous BC₂F₃ lines harboring the introgressed resistance genes through marker-assisted selection. This study demonstrates the effectiveness of integrating molecular marker-assisted selection with conventional breeding methods to enhance disease resistance while preserving high-yielding traits. The newly developed lines offer valuable material for future wheat improvement and contribute to sustainable agriculture and food security. Full article

Colorectal cancer (CRC) remains one of the most lethal malignancies worldwide, with high recurrence rates and limited curative options in metastatic settings. Cancer vaccines represent an emerging immunotherapeutic approach that aims to stimulate robust, tumor-specific immune responses. This review summarizes the current state of CRC vaccine development, including tumor cell-based, dendritic cell-based, peptide-based, nucleic acid-based (DNA and mRNA), and virus-based platforms. We highlight findings from key clinical trials that demonstrate immunogenicity, safety, and preliminary efficacy, with particular attention to combinations with chemotherapy and immune checkpoint inhibitors. Furthermore, we explore critical challenges such as tumor heterogeneity, immunosuppressive tumor microenvironments, and the logistical complexity; in this context, we particularly focus on the current development of personalized cancer vaccines, exploring the newly identified encouraging epitopes and their safety and efficacy in recent trials. The integration of cancer vaccines with in silico modeling, advanced delivery systems such as nanoparticles or AI-guided designs, and microbiome modulation represents a promising avenue for enhancing their clinical utility. Overall, therapeutic and prophylactic cancer vaccines may soon contribute meaningfully to the comprehensive management of CRC, especially in settings of minimal residual disease or early recurrence. Full article

Background/Objectives: Leukemia is associated with high recurrence rates and cancer vaccines are emerging as a promising immunotherapy against the disease. Here, we investigate the mechanism of action by which a personalized vaccine made from leukemia cells infected with an oncolytic virus (ICV) induces anti-tumor immunity. Methods: Using the L1210 murine model, leukemia cells were infected and irradiated to create the ICV. The CRISPR-Cas9 system was used to engineer knockout cells to test in treatment efficacy studies. Results: We found that pro-inflammatory interferons (IFNs) that are produced by infected vaccine cells induce the immunoproteasome (ImP), a specialized proteasome subtype that is found in immune cells. Interestingly, we show that while a vaccine using the oncolytic vesicular stomatitis virus (oVSV) completely protects against tumor challenge, the wild-type (wt) virus, which does not induce the ImP, is not as effective. To delineate the contribution of the ImP for vaccine efficacy, we generated ImP-knockout cell lines and found no differences in treatment efficacy compared to wild-type cells. Furthermore, an ICV using another murine leukemia model that expresses the ImP only when infected by an IFN gamma-encoding variant of the virus demonstrated similar efficacy as the parental virus. Conclusions: Taken together, our data show that ImP expression by vaccine cells was not required for the efficacy of leukemia ICVs. Full article

Background/Objectives: Pulmonary typical carcinoid (TC) is a rare type of primary neuroendocrine neoplasm of the lung with indolent behavior and a good prognosis. The main treatment strategy is surgery, the extent of which is controversial given the nature of the disease. The aim of this study is to assess whether the extent of resection influences survival and recurrence in patients undergoing lung resection and lymphadenectomy for TC and to investigate negative prognostic factors for OS. Methods: A single-centre retrospective study of 15 years’ experience was conducted. Data from all patients who underwent lung resection and lymphadenectomy for TC were collected. Patients were divided into two groups: anatomical and non-anatomical resections. Perioperative and long-term oncological results were analyzed. Results: In total, 115 patients were surgically treated for TC, of whom 83 (72%) underwent anatomical resection and 32 (28%) non-anatomical resection. Univariate analyses showed that age, left lower lobe, and many comorbidities had a detrimental effect on OS, whereas on multivariate analysis, only left lower lobe location and a high Charlson–Deyo comorbidity index (CCI) were confirmed as negative prognostic factors for OS. At a median follow-up of 93 months (IQR 57-129), the OS survival curves show a slightly lower trend for non-anatomical resections (p 0.152), while no differences were found for DFS. Conclusions: The results of this study confirm that in selected patients at risk for major resections, non-anatomical resection can be used to treat TC when R0 is achievable. These data, together with evidence from the literature, highlight the importance of patient-centred care in this rare disease. Full article

Downy mildew caused by Plasmopara viticola is an important disease in grape production, particularly in the highly susceptible, widely cultivated Vitis vinifera L. Breeding for disease resistance is an effective solution, and V. vinifera intraspecific crosses can yield progeny with both disease resistance and high quality. To assess the potential of intraspecific recurrent selection in V. vinifera (IRSV) in improving grapevine resistance to downy mildew and to analyze the pattern of disease resistance inheritance, the disease-resistant variety Ecolly was selected as one of the parents and crossed with Cabernet Sauvignon, Marselan, and Dunkelfelder, respectively, creating three reciprocal combinations, resulting in 1657 hybrid F1 progenies. The primary results are as follows: (1) significant differences in disease resistance among grape varieties and, significant differences in disease resistance between different vintages of the same variety were found; (2) the leaf downy mildew resistance levels of F1 progeny of different hybrid combinations conformed to a skewed normal distribution and showed some maternal dominance; (3) the degree of leaf bulbous elevation was negatively correlated with the level of leaf downy mildew resistance, and the correlation coefficient with the level of field resistance was higher; (4) five progenies with higher levels of both field and in vitro disease resistance were obtained. Intraspecific hybridization can improve the disease resistance of offspring through super-parent genetic effects, and Ecolly can be used as breeding material for recurrent hybridization to obtain highly resistant varieties. Full article

Background: Patients with resected stage IIB and IIC melanoma are at high risk of recurrence and distant metastasis, despite surgical treatment. The recent emergence of immune checkpoint inhibitors (ICIs) has led to their evaluation in the adjuvant setting for early-stage disease. This review aims to synthesize current evidence regarding adjuvant immunotherapy for stage IIB/IIC melanoma, explore emerging strategies, and highlight key challenges and future directions. Methods: We conducted a comprehensive literature review of randomized clinical trials, observational studies, and relevant mechanistic and biomarker research on adjuvant therapy in stage IIB/IIC melanoma. Particular focus was placed on pivotal trials evaluating PD-1 inhibitors (KEYNOTE-716 and CheckMate 76K), novel vaccine and targeted therapy trials, mechanisms of resistance, immune-related toxicity, and biomarker development. Results: KEYNOTE-716 and CheckMate 76K demonstrated significant improvements in recurrence-free survival (RFS) and distant metastasis-free survival (DMFS) with pembrolizumab and nivolumab, respectively, compared to placebo. However, no definitive overall survival benefit has yet been shown. Adjuvant immunotherapy is linked to immune-related adverse events, including permanent endocrinopathies. Emerging personalized approaches, such as circulating tumor DNA monitoring and gene expression profiling, may enhance patient selection, but remain investigational. Conclusions: Adjuvant PD-1 blockade offers clear RFS benefits in high-risk stage II melanoma, but optimal patient selection remains challenging, due to uncertain overall survival benefit and toxicity concerns. Future trials should integrate biomarker-driven approaches to refine therapeutic decisions and minimize overtreatment. Full article

Introduction: Primary hyperparathyroidism (pHPT) is an endocrine disorder characterized by excessive parathyroid hormone production, typically due to adenomas, hyperplasia, or carcinoma. Preoperative imaging plays a critical role in guiding surgical planning, particularly in selecting patients for minimally invasive procedures. While first-line imaging techniques, such as ultrasound and 99mTc-sestamibi scintigraphy, are standard, advanced second-line imaging modalities like 18F-fluorocholine PET/CT (FCH-PET) and four-dimensional computed tomography (4D-CT) have emerged as valuable tools when initial diagnostics are inconclusive. Methods: This article provides an updated review and recommendations of the role of these advanced imaging techniques in localizing parathyroid adenomas. Results: FCH-PET has shown exceptional sensitivity (94% per patient, 96% per lesion) and is particularly useful in detecting small or ectopic adenomas. Despite its higher sensitivity, it can yield false positives, particularly in the presence of thyroid disease. On the other hand, 4D-CT offers detailed anatomical imaging, aiding in the identification of parathyroids in challenging cases, including recurrent disease and ectopic glands. Studies suggest that FCH-PET and 4D-CT exhibit similar diagnostic performance and could be complementary in preoperative planning of most difficult situations. Conclusions: This article also emphasizes a multimodal approach, where initial imaging is followed by advanced techniques only in cases of uncertainty. Although 18F-fluorocholine PET/CT is favored as a second-line option, 4D-CT remains invaluable for its high spatial resolution and ability to guide surgery in complex cases. Despite limitations in evidence, these imaging modalities significantly enhance the accuracy of parathyroid localization, contributing to more targeted and minimally invasive surgery. Full article

Background/Objectives: Primary liver cancer (PLC), encompassing hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), constitutes a growing global health concern. Metabolic dysfunction-associated Steatotic Liver Disease (MASLD) and Type 2 diabetes mellitus (T2DM) represent a recurrent epidemiological overlap. Individuals with MASLD and T2DM (MASLD-T2DM) are at a higher risk of PLC. This scoping review highlights the epidemiological burden, the classic and novel pathogenetic frontiers, and the potential strategies optimizing the management of PLC in MASLD-T2DM. Methods: A systematic search of the PubMed, Medline, and SCOPUS electronic databases was conducted to identify evidence investigating the pathogenetic mechanisms linking MASLD and T2DM to hepatic carcinogenesis, highlighting the most relevant targets and the relatively emerging therapeutic strategies. The search algorithm included in sequence the filter words: “MASLD”, “liver steatosis”, “obesity”, “metabolic syndrome”, “body composition”, “insulin resistance”, “inflammation”, “oxidative stress”, “metabolic dysfunction”, “microbiota”, “glucose”, “immunometabolism”, “trained immunity”. Results: In the MASD-T2DM setting, insulin resistance (IR) and IR-induced mechanisms (including chronic inflammation, insulin/IGF-1 axis dysregulation, and autophagy), simultaneously with the alterations of gut microbiota composition and functioning, represent crucial pathogenetic factors in hepatocarcinogenesis. Besides, the glucose-related metabolic reprogramming emerged as a crucial pathogenetic moment contributing to cancer progression and immune evasion. In this scenario, lifestyle changes, simultaneously with antidiabetic drugs targeting IR-related effects and gut-liver axis, in parallel with novel approaches modulating immunometabolic pathways, represent promising strategies. Conclusions: Metabolic dysfunction, classically featuring MASLD-T2DM, constitutes a continuously expanding global issue, as well as a critical driver in PLC progression, demanding integrated and personalized interventions to reduce the future burden of disease. Full article

Colorectal cancer (CRC) is not only the third most common cancer worldwide, with 1.1 million new cases per year; it is also the second leading cause of cancer death. However, mortality has decreased since 2012 due to early detection programs and better therapeutic approaches. While many patients are diagnosed at an early stage, there is up to 50% relapse after optimal initial treatment. Therefore, it is crucial to explore the mechanism underlying the development of recurrences and metastasis. It is known that tumors release dormant cells that escape chemotherapy and nest in a target organ without proliferating. Under certain circumstances that are not yet entirely clear, they can be activated and metastasize. Therefore, the objective of this work is to explore the detailed mechanisms of dormancy, including early detection of recurrence and therapeutic approaches for the treatment of CRC. The specific objectives are to determine biomarkers that may be useful in identifying dormant cells to detect minimal residual disease (MRD) after surgery and predicting disease progression, as well as evaluating biomarkers that are susceptible to therapeutic intervention. Full article

Furunculosis caused by Aeromonas salmonicida poses a significant challenge to the sustainable production of maraena whitefish (Coregonus maraena). This case report outlines a multi-year disease management strategy at a European whitefish facility with two production departments, each specialising in different life-cycle stages. Recurrent outbreaks of A. salmonicida necessitated the development of effective vaccination protocols. Herd-specific immersion vaccines failed to confer protection, while injectable formulations with plant-based adjuvants caused severe adverse reactions and mortality rates exceeding 30%. In contrast, the bivalent vaccine Alpha Ject 3000, containing inactivated A. salmonicida and Vibrio anguillarum with a mineral oil adjuvant, yielded high tolerability and durable protection in over one million whitefish. Post-vaccination mortality remained low (3.3%), aligning with industry benchmarks, and furunculosis-related losses were fully prevented in both departments. Transcriptomic profiling of immune-relevant tissues revealed distinct gene expression signatures depending on vaccine type and time post-vaccination. Both the herd-specific vaccine and Alpha Ject 3000 induced the expression of immunoglobulin and inflammatory markers in the spleen, contrasted by reduced immunoglobulin transcript levels in the gills and head kidney together with the downregulated expression of B-cell markers. These results demonstrate that an optimised injectable vaccination strategy can significantly improve health outcomes and disease resilience in maraena whitefish aquaculture. Full article

Recurrent pregnancy loss (RPL) is defined as the occurrence of two or more pregnancy losses before 20 weeks of gestation. RPL is a common medical condition among reproductive-age women, with approximately 23 million cases reported annually worldwide. Up to 5% of pregnant women may experience two or more consecutive pregnancy losses. Previous studies have investigated risk factors for RPL, including maternal age, uterine pathology, genetic anomalies, infectious agents, endocrine disorders, thrombophilia, and immune dysfunction. However, RPL is a disease caused by a complex interaction of genetic factors, environmental factors (e.g., diet, lifestyle, and stress), epigenetic factors, and the immune system. In addition, due to the lack of research on genetics research related to RPL, the etiology remains unclear in up to 50% of cases. Platelets play a critical role in pregnancy maintenance. This study examined the associations of platelet receptor and ligand gene variants, including integrin subunit beta 3 (ITGB3) rs2317676 A > G, rs3809865 A > T; fibrinogen gamma chain (FGG) rs1049636 T > C, rs2066865 T > C; glycoprotein 1b subunit alpha (GP1BA) rs2243093 T > C, rs6065 C > T; platelet endothelial cell adhesion molecule 1 (PECAM1) rs2812 C > T; and platelet endothelial aggregation receptor 1 (PEAR1) rs822442 C > A, rs12137505 G > A, with RPL prevalence. In total, 389 RPL patients and 375 healthy controls (all Korean women) were enrolled. Genotyping of each single nucleotide polymorphism was performed using polymerase chain reaction–restriction fragment length polymorphism and the TaqMan genotyping assay. All samples were collected with approval from the Institutional Review Board at Bundang CHA Medical Center. The ITGB3 rs3809865 A > T genotype was strongly associated with RPL prevalence (pregnancy loss [PL] ≥ 2: adjusted odds ratio [AOR] = 2.505, 95% confidence interval [CI] = 1.262–4.969, p = 0.009; PL ≥ 3: AOR = 3.255, 95% CI = 1.551–6.830, p = 0.002; PL ≥ 4: AOR = 3.613, 95% CI = 1.403–9.307, p = 0.008). The FGG rs1049636 T > C polymorphism was associated with a decreased risk in women who had three or more pregnancy losses (PL ≥ 3: AOR = 0.673, 95% CI = 0.460–0.987, p = 0.043; PL ≥ 4: AOR = 0.556, 95% CI = 0.310–0.997, p = 0.049). These findings indicate significant associations of the ITGB3 rs3809865 A > T and FGG rs1049636 T > C polymorphisms with RPL, suggesting that platelet function influences RPL in Korean women. Full article

Chronic nasopharyngeal and otic disorders in children represent a significant clinical challenge due to their multifactorial etiology, variable presentation, and frequent resistance to standard therapies. Although often approached from a symptomatic or anatomical perspective, these conditions are deeply rooted in histological and molecular alterations that sustain inflammation, impair mucosal function, and promote recurrence. This narrative review synthesizes the current knowledge on the normal histology of the nasopharynx, Eustachian tube, and middle ear, and explores key pathophysiological mechanisms, including epithelial remodeling, immune cell infiltration, cytokine imbalance, and tissue fibrosis. Special emphasis is placed on the role of immunohistochemistry in defining inflammatory phenotypes, barrier dysfunction, and remodeling pathways. The presence of biofilm, epithelial plasticity, and dysregulated cytokine signaling are also discussed as contributors to disease chronicity. These findings have direct implications for diagnosis, therapeutic stratification, and postoperative monitoring. By integrating histological, immunological, and molecular data, clinicians can better characterize disease subtypes, anticipate treatment outcomes, and move toward a more personalized and biologically informed model of pediatric ENT care. Full article