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Povzetek: Introduction: Inflammation occurs in the initial stage of arterial atherosclerosis and serves as the first step in thrombus generation, with elevated inflammatory markers predicting myocardial infarction in coronary artery disease patients. Inflammation is known to alter the course of multiple diseases and can thus, also impact recovery post-treatment and surgical outcomes. Yet, there is a paucity of data regarding the relationship between inflammatory biomarkers and arterial thrombotic potential in peripheral artery disease (PAD) patients post-revascularization. Our pilot study attempts to fill this gap by evaluating if the expression of inflammatory biomarkers in PAD patients correlates with the incidence of thrombotic events post-revascularization. Methods: Plasma samples were prospectively collected from PAD patients who underwent revascularization from 2021 to 2023 at monthly time points for 6 months from the procedure. Patients were followed for a total of 6 months post-procedure and those who experienced thrombotic events were identified. Nine patients with thrombotic events and 16 with non-thrombotic events along with 5 healthy volunteers were analyzed. Plasma samples were analyzed for the following pro-inflammatory markers: IL-1β (Interleukin-1 beta), IL-6, and TNF-α (Tumor Necrosis Factor - alpha), GM-CSF (Granulocyte-Macrophage Colony-Stimulating Factor), IFNγ (Interferon-gamma), IL-8, MCP-1 (Monocyte Chemoattractant Protein-1). The Kruskal-Wallis test was performed to compare bio-inflammatory marker levels between groups. Results: A total of 303 patients were enrolled, of which 59 had thrombotic events. There were no differences between medications or disease burden between groups. Levels of circulating IL-6 and TNF- α were significantly higher in the thrombosis cohort compared to the non-thrombosis cohort (55 vs. 38, p < 0.02) and (159 vs. 110, p < 0.02) respectively. Although there was a trend toward significance for IL-1β between the thrombotic cohort and non-thrombotic cohort, it did not reach statistical significance (18 vs. 11.5, p = NS). There was no difference observed in aspirin's ability to dampen the inflammatory response between the two groups as all patients were on aspirin between the groups evaluated. Conclusion: Pro-inflammatory markers IL-6 and TNF-α are significantly increased in patients, 1 month prior to an arterial thrombotic event, as compared to patients without thrombotic events. These biomarkers could predict impending thrombosis in patients with PAD post-revascularization.
Ključne besede: inflammation, interleukin-6, peripheral artery disease (PAD), thrombosis, tumor necrosis factor-alpha
Objavljeno v DiRROS: 11.12.2025; Ogledov: 223; Prenosov: 74
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Povzetek: The aim of the study was to evaluate interobserver variability in the determination of the primary tumor for radiotherapy treatment planning in esophageal squamous cell carcinoma (ESCC). Methods: Sixteen patients with locally advanced ESCC were included in the analysis. In all patients positron emission tomography with computed tomography (PETC/CT) and magnetic resonance (MR) scans for radiotherapy planning were performed. Five experienced radiation oncologists delineated the primary tumor based on CT alone, MR alone, PET/CT, CT with fused MR and PET/CT with fused MR. Mean tumor volumes were calculated for each patient and imaging modality. The generalized conformity index (CIgen) was calculated to assess agreement in tumor determination. Results: The mean tumor volumes and CIgen for CT alone, MR alone, PET/CT, CT with fused MR and PET/CT with fused MR were 33.1 cm3, 30.2 cm3, 38.1 cm3, 31.9 cm3, 36.2 cm3 and 0.59, 0.64, 0.66, 0.63, 0.71, respectively. CIgen was significantly higher using PET/CT with fused MR compared to CT (p < 0.001) and PET/CT (p = 0.002) and using PET/CT compared to CT (alone) (p = 0.003). Conclusions: Our study showed higher agreement in primary tumor determination in ESCC using PET/CT compared to CT alone. Higher agreement was also found using PET/CT with fused MR compared to CT alone and PET/CT.
Ključne besede: magnetic resonance, positron emission tomography, squamous cell carcinoma, primary tumor
Objavljeno v DiRROS: 26.11.2025; Ogledov: 206; Prenosov: 83
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Povzetek: Medulloblastoma (MB) is the most malignant childhood brain cancer. Group 3 MB (G3 MB) subtype accounts for about 25% of MB and is associated with the worst outcomes. Herein, we report that more than half of G3 MB tumors express melanoma antigens (MAGEs), which are potential prognostic and therapeutic markers. MAGEs are cancer‑testis antigens, aberrantly expressed in several adult cancers, and associated with poorer prognosis and therapy resistance; however, their role in pediatric cancers is mostly unknown. This study aimed to determine whether MAGEs are activated and important in pediatric MB. We obtained formalin‑fixed paraffin‑embedded tumor samples of 34 patients, collected between 2008 and 2015 at the Children’s Medical Center in Dallas and applied our validated reverse transcription quantitative PCR (RT‑qPCR) assay to measure the expression of 23 MAGE genes. To validate our data, we analyzed published datasets from pediatric MB tumors and patient‑derived orthotopic xenografts, totaling 949 patients. Our RT‑qPCR analysis suggested that MAGEs were expressed in G3/4MB. Further mining of bulk and single‑cell RNA‑sequencing datasets confirmed that 50–75% of G3 tumors activate several MAGEs. Intriguingly, single‑cell data analysis showed that MAGEs are expressed in distinct subsets of cells in MAGE‑positive tumors and are not activated in mouse genetic models, suggesting they contribute to the tumor heterogeneity and species‑specificity of G3 MB. We then examined how MAGE expression affects the growth and oncogenic potential by CRISPR‑Cas9‑ and siRNA‑mediated gene depletion. Depletion of MAGEAs, ‑B2, and ‑Cs altered cell survival, viability, and clonogenic growth due to decreased proliferation and increased apoptosis of MAGE‑positive MB cells. These findings suggested that targeting MAGEs could represent a viable therapeutic strategy for G3 MB. A deeper understanding of MAGE regulation and function is warranted and could aid in improving prognostic and therapeutic approaches for this poorly characterized subgroup of pediatric brain tumors.
Ključne besede: medulloblastoma, tumor antigens, MAGE, pediatric cancer, cancer‑testis antigens
Objavljeno v DiRROS: 19.09.2025; Ogledov: 368; Prenosov: 168
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Povzetek: The gut microbiome, a diverse community of microorganisms in the human body, plays an important role in maintaining health and influences various processes such as digestion, immunity, and protection against pathogens. A person's unique gut microbiome, shaped by factors such as birth method, diet, antibiotics, and lifestyle, contributes to bodily functions such as nutrient metabolism, drug processing, and im-mune regulation. Changes in the gut microbiome are associated with a predisposition to cancer and can influence the effectiveness of cancer treatments. Dysbiosis in the gut microbiome can lead to inflammation, tumor development, and metastasis, highlight-ing its importance in cancer research and prevention. The gut microbiota significantly influences cancer development and treatment outcomes. Certain bacteria enhance the effects of therapies such as cyclophosphamide and contribute to the body's im-mune response against tumors. Microbes produce anti-cancer molecules and probiotic compounds, making them potential tools in cancer prevention and treatment. Future research aims to develop targeted antibiotics and explore fecal microbiota transfer to selectively manipulate the microbiota for improved cancer treatment. Due to genetic and physiological similarities, mouse models are invaluable in biomedical research. However, because the gut microbiome of humans and mice and the composition of the tumor microenvironment differ, direct comparison between these two models can be challenging in research. Bridging these gaps is crucial for comparative medicine, especially in cancer research where the microbiome plays an important role in treat-ment outcomes. One important area where the gut microbiome could offer potential new treatment options is in primary brain tumors such as gliomas. To date, there are no long-lasting effective treatments for this type of cancer, but research in mouse models shows a link between tumor progression and response to treatment with changes in the gut microbiome. Overall, the gut microbiome and its modulation represent an opportu-nity for more efficient future cancer treatment.
Ključne besede: gut microbiome, cancer, treatment outcome, tumor models, glioma
Objavljeno v DiRROS: 03.04.2025; Ogledov: 847; Prenosov: 378
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Povzetek: Glioblastoma is the most lethal primary brain tumor and poor survival of glioblastoma patients is attributed to the presence of glioma stem cells (GSCs). These therapy-resistant, quiescent and pluripotent cells reside in GSC niches, which are specific microenvironments that protect GSCs against radiotherapy and chemotherapy. We previously showed the existence of hypoxic peri-arteriolar GSC niches in glioblastoma tumor samples. However, other studies have described peri-vascular niches, peri-hypoxic niches, peri-immune niches and extracellular matrix niches of GSCs. The aim of this review was to critically evaluate the literature on these five different types of GSC niches. In the present review, we describe that the five niche types are not distinct from one another, but should be considered to be parts of one integral GSC niche model, the hypoxic peri-arteriolar GSC niche. Moreover, hypoxic peri-arteriolar GSC niches are structural and functional look-alikes of hematopoietic stem cell (HSC) niches in the bone marrow. GSCs are maintained in peri-arteriolar niches by the same receptor-ligand interactions as HSCs in bone marrow. Our concept should be rigidly tested in the near future and applied to develop therapies to expel and keep GSCs out of their protective niches to render them more vulnerable to standard therapies.
Ključne besede: glioblastoma, glioma stem cells, niches, blood vessels, extracellular matrix, tumor microenvironment, hypoxia, therapy resistance, vasculature
Objavljeno v DiRROS: 06.08.2024; Ogledov: 1103; Prenosov: 757
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