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Biomolecules & Biomedicine Jun 2024Cerebral aneurysms (CA) are critical conditions often associated with oxidative stress in vascular endothelial cells (VECs). The enzyme lactate dehydrogenase A (LDHA)...
Cerebral aneurysms (CA) are critical conditions often associated with oxidative stress in vascular endothelial cells (VECs). The enzyme lactate dehydrogenase A (LDHA) plays a crucial role in glycolysis and lactate metabolism, processes implicated in the pathogenesis of aneurysms. Understanding these molecular mechanisms can inform the development of novel therapeutic targets. This study investigated the role of lactate metabolism and lactate-related genes, particularly LDHA and vascular endothelial growth factor A (VEGFA) genes, in VECs during oxidative stress. Using the GSE26969 dataset, we identified differential expression of lactate-related genes and performed functional enrichment analysis, revealing significant associations with glycolysis and lactate metabolic pathways. To induce oxidative stress, VECs were treated with H2O2, and the expression of LDHA and VEGFA was analyzed using quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting (WB) assays. Under oxygen-glucose deprivation/reperfusion (OGD/R) conditions, the effects of LDHA overexpression and VEGFA knockdown on cell viability and apoptosis were evaluated. Immunoprecipitation combined with western blotting was used to detect the lactylation status of LDHA following OGD/R stimulation and treatment with lactic acid (LA) and 2-deoxyglucose (2-DG). Our results indicated that oxidative stress modulates LDHA expression, glucose uptake, and lactate production, suggesting a metabolic shift towards glycolysis. LDHA overexpression improved cell survival and reduced apoptosis, while VEGFA knockdown had the opposite effect. Additionally, 2-DG treatment reduced LDHA lactylation and apoptosis. Our findings demonstrated that LDHA plays a critical role in the oxidative stress response of VECs, highlighting the potential therapeutic value of targeting glycolysis in CA. This study contributes to the understanding of metabolic adaptations in vascular pathologies and suggests new avenues for therapeutic intervention in CA management.
PubMed: 38829380
DOI: 10.17305/bb.2024.10510 -
Frontiers in Oncology 2024Since the first report, primary mediastinal seminoma has a low incidence in the population, and it mainly affects young and middle-aged men, is clinically rare, and...
INTRODUCTION
Since the first report, primary mediastinal seminoma has a low incidence in the population, and it mainly affects young and middle-aged men, is clinically rare, and accounts for a very small proportion of mediastinal tumors. In this study, we describe the first case of primary mediastinal seminoma with azoospermia and hypothesize that the coexistence of the two disorders may not be a coincidence.
CASE REPORT
A 16-year-old man presented with chest tightness and chest pain, a mediastinal mass on chest CT, and abnormal 18F-fluoro-deoxyglucose uptake on a PET-CT scan. By biopsy of the mass, the pathological diagnosis was a primary mediastinal seminoma. Because chemotherapy is included in the treatment of the tumor, the patient underwent sperm freezing before treatment, considering that chemotherapy can affect fertility, but the patient was diagnosed with azoospermia. Finally, the patient underwent tumor resection and postoperative chemotherapy. No tumor recurrence was observed at the current follow-up.
CONCLUSION
Primary mediastinal seminoma is mainly confirmed by histopathological examination, and surgery and chemoradiotherapy are the current treatments. In patients with mediastinal seminoma or azoospermia, doctors should be aware that the two disorders may coexist, especially in men who have fertility requirements or long-term infertility, and that examination of the mediastinum and semen may lead to unexpected findings in the diagnosis and treatment. For mediastinal germ cell tumors, genetic testing is of great value in the treatment of tumors and the prediction of associated diseases. Future studies exploring the potential correlation between mediastinal seminoma and azoospermia will be prospective.
PubMed: 38826789
DOI: 10.3389/fonc.2024.1309803 -
Journal of Musculoskeletal & Neuronal... Jun 2024Increasingly Charcot neuroarthropathy (CN) is being recognized in patients with Charcot-Marie-Tooth (CMT) disease. In this report, we describe a case of CN in a CMT...
Increasingly Charcot neuroarthropathy (CN) is being recognized in patients with Charcot-Marie-Tooth (CMT) disease. In this report, we describe a case of CN in a CMT patient, adding to the very scarce literature describing this association. We additionally report his unique evaluation with fluorodeoxyglucose (FDG) and sodium fluoride (NaF) positron emission tomography/computed tomography (PET/CT) scanning, the study of which is limited in CN despite its promising role. A 54-year-old known case of CMT, presented with left foot pain, and swelling for 4 months. Weakness and sensory deficits as a result of CMT were evident in both lower and upper limbs. His x-ray was suggestive of CN. Both FDG and NaF PET/CT scanning demonstrated increased tracer uptake in the first tarsometatarsal joint (TMTJ), in keeping with CN. Recognition of the association of CMT with CN is of vital importance as early diagnosis relies on high clinical suspicion. Characterizing risk factors of CN in CMT patients is still under study. Moreover, there is lack of data evaluating the role of PET/CT in CN and specifically in the context of CMT.
Topics: Humans; Charcot-Marie-Tooth Disease; Middle Aged; Positron Emission Tomography Computed Tomography; Male; Fluorodeoxyglucose F18; Sodium Fluoride; Arthropathy, Neurogenic; Radiopharmaceuticals
PubMed: 38826006
DOI: No ID Found -
Scientific Reports Jun 2024The aim of the study was to assess healthy tissue metabolism (HTM) using 2-deoxy-2-[F]fluoro-D-glucose ([F]FDG) positron emission tomography/computed tomography (PET/CT)...
The aim of the study was to assess healthy tissue metabolism (HTM) using 2-deoxy-2-[F]fluoro-D-glucose ([F]FDG) positron emission tomography/computed tomography (PET/CT) during chemotherapy in Hodgkin lymphoma (HL) and the association of HTM with baseline metabolic tumour volume (MTV), haematological parameters, adverse events (AEs), early response and progression-free survival (PFS). We retrospectively identified 200 patients with advanced HL from the RATHL trial with [F]FDG-PET/CT before (PET0) and following 2 cycles of chemotherapy (PET2). [F]FDG-uptake was measured in bone marrow (BM), spleen, liver and mediastinal blood pool (MBP). Deauville score (DS) 1-3 was used to classify responders and DS 4-5, non-responders. [F]FDG-uptake decreased significantly in BM and spleen and increased in liver and MBP at PET2 (all p < 0.0001), but was not associated with MTV. Higher BM uptake at PET0 was associated with lower baseline haemoglobin and higher absolute neutrophil counts, platelets, and white blood cells. High BM, spleen, and liver uptake at PET0 was associated with neutropenia after cycles 1-2. BM uptake at PET0 was associated with treatment failure at PET2 and non-responders with higher BM uptake at PET2 had significantly inferior PFS (p = 0.023; hazard ratio = 2.31). Based on these results, we concluded that the change in HTM during chemotherapy was most likely a direct impact of chemotherapy rather than a change in MTV. BM uptake has prognostic value in HL.
Topics: Humans; Hodgkin Disease; Fluorodeoxyglucose F18; Positron Emission Tomography Computed Tomography; Male; Female; Adult; Middle Aged; Prognosis; Retrospective Studies; Young Adult; Bone Marrow; Aged; Liver; Adolescent; Radiopharmaceuticals; Spleen
PubMed: 38824206
DOI: 10.1038/s41598-024-63349-5 -
Nature Communications May 2024Minimally invasive thermal therapy is a successful alternative treatment to surgery in solid tumors with high complete ablation rates, however, tumor recurrence remains...
Minimally invasive thermal therapy is a successful alternative treatment to surgery in solid tumors with high complete ablation rates, however, tumor recurrence remains a concern. Central memory CD8 T cells (T) play important roles in protection from chronic infection and cancer. Here we find, by single-cell RNA analysis of human breast cancer samples, that although the memory phenotype of peripheral CD8 T cells increases slightly after microwave ablation (MWA), the metabolism of peripheral CD8 T cells remains unfavorable for memory phenotype. In mouse models, glycolysis inhibition by 2-deoxy-D-glucose (2DG) in combination with MWA results in long-term anti-tumor effect via enhancing differentiation of tumor-specific CD44CD62LCD8 T cells. Enhancement of CD8 T cell differentiation determined by Stat-1, is dependent on the tumor-draining lymph nodes (TDLN) but takes place in peripheral blood, with metabolic remodeling of CD8 T cells lasting the entire course of the the combination therapy. Importantly, in-vitro glycolysis inhibition in peripheral CD8 T cells of patients with breast or liver tumors having been treated with MWA thrice leads to their differentiation into CD8 T cells. Our work thus offers a potential strategy to avoid tumor recurrence following MWA therapy and lays down the proof-of-principle for future clinical trials.
Topics: Glycolysis; Animals; CD8-Positive T-Lymphocytes; Humans; Cell Differentiation; Mice; Female; Breast Neoplasms; Microwaves; Immunologic Memory; Deoxyglucose; Cell Line, Tumor; Liver Neoplasms; Memory T Cells
PubMed: 38821965
DOI: 10.1038/s41467-024-49059-6 -
Anticancer Research Jun 2024This study analyzed the effect of epidermal growth factor receptor (EGFR) mutations on fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography...
BACKGROUND/AIM
This study analyzed the effect of epidermal growth factor receptor (EGFR) mutations on fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (F-18 FDG PET/CT) results in lung cancer and the pathological findings in patients subjected to surgery.
PATIENTS AND METHODS
A total of 210 patients diagnosed with lung cancer by F-18 FDG PET/CT at Inje University Busan Paik Hospital between January 2018 and December 2023 were recruited. EGFR mutation tests were performed on biopsy specimens. Overall, 78 patients (37.1%) with EGFR mutations were included in this study. Twenty-seven patients (12.9%) had distant metastases at the time of diagnosis. Of all patients, 69 (32.9%) underwent surgery at our hospital, and their pathological findings were analyzed.
RESULTS
The maximum standardized uptake value (SUVmax) of F-18 FDG PET/CT was <10 in patients with EGFR mutations. Patients with EGFR mutations were not commonly diagnosed with diabetes. When analyzing the pathological findings after surgery in the 69 patients, adenocarcinoma was more common in those with EGFR mutations. In contrast, perineural invasion was more common in patients without EGFR mutations. When analyzing the results of 69 patients with postoperative pathology, 25 relapsed during the median follow-up of 21.7 months (range=0.9-58.4 months). Patients who underwent surgery and had EGFR mutations (n=26) exhibited lower recurrence rates compared to those without EGFR mutations. Disease-free survival was longer in patients with EGFR mutations.
CONCLUSION
In non-small-cell lung cancer with an EGFR mutation, the F-18 FDG PET/CT SUVmax value and the probability of recurrence were lower. EGFR mutations are associated with low-glucose metabolism.
Topics: Humans; Lung Neoplasms; ErbB Receptors; Positron Emission Tomography Computed Tomography; Male; Female; Mutation; Middle Aged; Aged; Fluorodeoxyglucose F18; Adult; Aged, 80 and over; Radiopharmaceuticals; Carcinoma, Non-Small-Cell Lung
PubMed: 38821597
DOI: 10.21873/anticanres.17075 -
European Journal of Radiology Jul 2024The objective of this study was to preliminarily assess the ability of metabolic parameters and radiomics derived from F-fluorodeoxyglucose positron emission...
PURPOSE
The objective of this study was to preliminarily assess the ability of metabolic parameters and radiomics derived from F-fluorodeoxyglucose positron emission tomography/computed tomography (F-FDG PET/CT) to distinguish mass-forming pancreatic lymphoma from pancreatic carcinoma using machine learning.
METHODS
A total of 88 lesions from 86 patients diagnosed as mass-forming pancreatic lymphoma or pancreatic carcinoma were included and randomly divided into a training set and a validation set at a 4-to-1 ratio. The segmentation of regions of interest was performed using ITK-SNAP software, PET metabolic parameters and radiomics features were extracted using 3Dslicer and PYTHON. Following the selection of optimal metabolic parameters and radiomics features, Logistic regression (LR), support vector machine (SVM), and random forest (RF) models were constructed for PET metabolic parameters, CT radiomics, PET radiomics, and PET/CT radiomics. Model performance was assessed in terms of area under the curve (AUC), accuracy, sensitivity, and specificity in both the training and validation sets.
RESULTS
Strong discriminative ability observed in all models, with AUC values ranging from 0.727 to 0.978. The highest performance exhibited by the combined PET and CT radiomics features. AUC values for PET/CT radiomics models in the training set were LR 0.994, SVM 0.994, RF 0.989. In the validation set, AUC values were LR 0.909, SVM 0.883, RF 0.844.
CONCLUSION
Machine learning models utilizing the metabolic parameters and radiomics of F-FDG PET/CT show promise in distinguishing between pancreatic carcinoma and mass-forming pancreatic lymphoma. Further validation on a larger cohort is necessary before practical implementation in clinical settings.
Topics: Humans; Fluorodeoxyglucose F18; Pancreatic Neoplasms; Positron Emission Tomography Computed Tomography; Machine Learning; Male; Female; Middle Aged; Diagnosis, Differential; Radiopharmaceuticals; Lymphoma; Aged; Sensitivity and Specificity; Adult; Reproducibility of Results; Aged, 80 and over
PubMed: 38820949
DOI: 10.1016/j.ejrad.2024.111531 -
BMJ Open May 2024Fluorine-fluorodeoxyglucose (F-FDG) positron emission tomography (PET) CT imaging has been used in many inflammatory and infectious conditions to differentiate areas of...
Can FDG-PET/CT imaging be used to predict decline in quality of life in interstitial lung disease? A prospective study of the relationship between FDG uptake and quality of life in a UK outpatient setting.
BACKGROUND
Fluorine-fluorodeoxyglucose (F-FDG) positron emission tomography (PET) CT imaging has been used in many inflammatory and infectious conditions to differentiate areas of increased metabolic activity. FDG uptake differs between areas of normal lung parenchyma and interstitial lung disease (ILD).
OBJECTIVES
In this study, we investigated whether FDG-PET/CT parameters were associated with a change in the quality of life (QoL) in patients with ILD over 4 years of follow-up.
METHODS
Patients underwent PET-CT imaging at diagnosis and were followed up with annual QoL assessment using the St George's Respiratory Questionnaire (SGRQ) until death or 4 years of follow-up. Maximum standard uptake value (SUVmax) and Tissue-to-Background Ratio (TBR) were assessed against SGRQ overall and subscale scores.
RESULTS
193 patients (94 patients in the idiopathic pulmonary fibrosis (IPF) subgroup and 99 patients in the non-IPF subgroup) underwent baseline FDG-PET/CT imaging and QoL assessment. Weak-to-moderate correlation was observed between baseline SUVmax and SGRQ scores in both ILD subgroups. No relationship was observed between baseline SUVmax or TBR and change in SGRQ scores over 4 years of follow-up. In the IPF subgroup, surviving patients reported a decline in QoL at 4 years post diagnosis whereas an improvement in QoL was seen in surviving patients with non-IPF ILD.
CONCLUSIONS
Weak-to-moderate positive correlation between baseline SUVmax and SGRQ scores was observed in both ILD subgroups (IPF:r=0.187, p=0.047, non-IPF: r=0.320, p=0.001). However, baseline SUVmax and TBR were not associated with change in QoL in patients with IPF and non-IPF ILD over 4 years of follow-up. At 4 years post diagnosis, surviving patients with IPF reported declining QoL whereas improvement was seen in patients with ILD who did not have IPF.
Topics: Humans; Fluorodeoxyglucose F18; Positron Emission Tomography Computed Tomography; Quality of Life; Male; Female; Lung Diseases, Interstitial; Prospective Studies; Aged; Middle Aged; United Kingdom; Radiopharmaceuticals; Surveys and Questionnaires; Idiopathic Pulmonary Fibrosis
PubMed: 38816048
DOI: 10.1136/bmjopen-2023-081103 -
Turkish Journal of Medical Sciences 2024The aim of this study is to evaluate the baseline F18-FDG PET/CT findings of individuals diagnosed with giant cell arteritis (GCA) and to explore its association with...
BACKGROUND/AIM
The aim of this study is to evaluate the baseline F18-FDG PET/CT findings of individuals diagnosed with giant cell arteritis (GCA) and to explore its association with clinical findings and classification criteria.
MATERIALS AND METHODS
We analysed data from patients who underwent F18-FDG PET/CT scans to investigate large vessel (LV) involvement between 2010 and 2019. Only patients with a clinical diagnosis of GCA and at least 6 months of follow-up were included. We compared initial clinical features and laboratory findings based on the presence of LV vasculitis on PET/CT and the maximum standard uptake value (SUVmax) of vascular territories.
RESULTS
Twenty-nine patients (median age at diagnosis: 70, F/M: 24/5) were included in the study. Among them, 21 patients (72.4%) presented with cranial symptoms, while 8 patients (27.5%) had isolated LV-GCA. Twenty-two patients (75.9%) met the ACR/EULAR 2022 GCA classification criteria. LV vasculitis was detected on PET/CT in 23 patients (79.3%). A positive correlation was observed between SUVmax in the thoracic aorta and both CRP and ESR levels (r = 0.50, p = 0.026 and r = 0.63, p = 0.002, respectively). PET/CT positive patients were found to be younger (p = 0.016) and more frequently female (p = 0.017). They also exhibited fewer headaches (56.5% vs. 100%, p = 0.04), experienced fewer flares during follow-up (p = 0.03), and had a lower cumulative glucocorticoid dose at the 6th month (p = 0.036). Comparison of PET/CT-positive patients (n = 23) based on the fulfilment of the ACR/EULAR 2022 classification criteria revealed that patients who met these criteria were older (p = 0.02) and had significantly lower CRP levels at diagnosis (p = 0.02).
CONCLUSION
The performance of F18-FDG PET/CT in diagnosing LV involvement in GCA is favourable, and the severity of FDG uptake in the vessel wall correlates with the acute phase response. Patients with extracranial involvement on PET/CT exhibit distinct features, including a younger age and female predominance. Additionally, these patients appear to experience fewer relapses and require lower doses of glucocorticoids. However, the clinical significance of PET/CT in patients who met ACR/EULAR classification criteria, predominantly consisting of patients with ischemic cranial symptoms, could not be determined in our study.
Topics: Humans; Giant Cell Arteritis; Female; Fluorodeoxyglucose F18; Male; Aged; Positron Emission Tomography Computed Tomography; Middle Aged; Radiopharmaceuticals; Aged, 80 and over; Retrospective Studies
PubMed: 38812633
DOI: 10.55730/1300-0144.5767 -
Alzheimer Disease and Associated...Individuals with behavioral-variant frontotemporal dementia (bvFTD) show changes in brain structure as assessed by MRI and brain function assessed by 18FDG-PET...
PURPOSE
Individuals with behavioral-variant frontotemporal dementia (bvFTD) show changes in brain structure as assessed by MRI and brain function assessed by 18FDG-PET hypometabolism. However, current understanding of the spatial and temporal interplay between these measures remains limited.
METHODS
Here, we examined longitudinal atrophy and hypometabolism relationships in 15 bvFTD subjects with 2 to 4 follow-up MRI and PET scans (56 visits total). Subject-specific slopes of atrophy and hypometabolism over time were extracted across brain regions and correlated with baseline measures both locally, via Pearson correlations, and nonlocally, via sparse canonical correlation analyses (SCCA).
RESULTS
Notably, we identified a robust link between initial hypometabolism and subsequent cortical atrophy rate changes in bvFTD subjects. Network-level exploration unveiled alignment between baseline hypometabolism and ensuing atrophy rates in the dorsal attention, language, and default mode networks. SCCA identified 2 significant and highly localized components depicting the connection between baseline hypometabolism and atrophy slope over time. The first centered around bilateral orbitofrontal, frontopolar, and medial prefrontal lobes, whereas the second concentrated in the left temporal lobe and precuneus.
CONCLUSIONS
This study highlights 18FDG-PET as a dependable predictor of forthcoming atrophy in spatially adjacent brain regions for individuals with bvFTD.
Topics: Humans; Frontotemporal Dementia; Atrophy; Positron-Emission Tomography; Male; Female; Magnetic Resonance Imaging; Middle Aged; Aged; Brain; Fluorodeoxyglucose F18; Longitudinal Studies
PubMed: 38812447
DOI: 10.1097/WAD.0000000000000611