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Biomedicine & Pharmacotherapy =... Jul 2024Metastasis is the leading cause of cancer-related deaths, making the development of novel, more effective therapies imperative to alleviate patient suffering. Metabolic...
Metastasis is the leading cause of cancer-related deaths, making the development of novel, more effective therapies imperative to alleviate patient suffering. Metabolic switching is a hallmark of cancer cells that facilitates metastasis. Cancer cells obtain most of their energy and intermediate metabolites, which are required to proliferate and metastasize, through aerobic glycolysis. Previous work from our laboratory has shown that Caveolin-1 (CAV1) expression in cancer cells promotes glycolysis and metastasis. Here, we sought to determine if limiting glycolysis reduced CAV1-enhanced metastasis and to identify the mechanism(s) involved. We evaluated the effects of the glycolysis inhibitor 2-deoxy-D-glucose (2-DG) in metastatic melanoma and breast cancer cell lines expressing or not CAV1. Non-cytotoxic concentrations of 2-DG (1 mM) inhibited the migration of B16-F10 melanoma and MDA-MB-231 breast cancer cells. CAV1-mediated activation of Src/Akt signaling was required for CAV1-enhanced migration and was blocked in the presence of 2-DG. Moreover, inhibition of Akt reduced CAV1-enhanced lung metastasis of B16-F10 cells. Collectively, these findings highlight the importance of CAV1-induced metabolic reprogramming for metastasis and point towards possible therapeutic approaches to prevent metastatic disease by inhibiting glycolysis and Src/Akt signaling.
Topics: Caveolin 1; Glycolysis; Proto-Oncogene Proteins c-akt; Animals; Signal Transduction; src-Family Kinases; Humans; Cell Line, Tumor; Mice; Cell Movement; Deoxyglucose; Female; Neoplasm Metastasis; Melanoma, Experimental; Breast Neoplasms; Lung Neoplasms; Mice, Inbred C57BL
PubMed: 38834004
DOI: 10.1016/j.biopha.2024.116841 -
Clinical Imaging Aug 2024This meta-analysis aimed to compare the diagnostic effectiveness of [F]FDG PET/CT with that of [F]FDG PET/MRI in terms of identifying liver metastasis in patients with... (Comparative Study)
Comparative Study Meta-Analysis
PURPOSE
This meta-analysis aimed to compare the diagnostic effectiveness of [F]FDG PET/CT with that of [F]FDG PET/MRI in terms of identifying liver metastasis in patients with primary cancer.
METHODS
PubMed, Embase, Web of Science, and the Cochrane Library were searched, and studies evaluating the diagnostic efficacy of [F]FDG PET/CT and [F]FDG PET/MRI in patients with liver metastasis of primary cancer were included. We used a random effects model to analyze their sensitivity and specificity. Subgroup analyses and corresponding meta-regressions focusing on race, image analysis, study design, and analysis methodologies were conducted. Cochrane Q and I statistics were used to assess intra-group and inter-group heterogeneity.
RESULTS
Seven articles with 343 patients were included in this meta-analysis. The sensitivity of [F]FDG PET/CT was 0.82 (95 % CI: 0.63-0.96), and that of [F]FDG PET/MRI was 0.91 (95 % CI: 0.82-0.98); there was no significant difference between the two methods (P = 0.32). Similarly, both methods showed equal specificity: 1.00 (95 % CI: 0.95-1.00) for [F]FDG PET/CT and 1.00 (95 % CI: 0.96-1.00) for [F]FDG PET/MRI, and thus, there was no significant difference between the methods (P = 0.41). Furthermore, the subgroup analyses revealed no differences. Meta-regression analysis revealed that race was a potential source of heterogeneity for [F]FDG PET/CT (P = 0.01), while image analysis and contrast agent were found to be potential sources of heterogeneity for [18F]FDG PET/MRI (P = 0.02).
CONCLUSIONS
[F]FDG PET/MRI has similar sensitivity and specificity to [F]FDG PET/CT for detecting liver metastasis of primary cancer in both the general population and in subgroups. [F]FDG PET/CT may be a more cost-effective option. However, the conclusions of this meta-analysis are tentative due to the limited number of studies included, and further research is necessary for validation.
Topics: Humans; Fluorodeoxyglucose F18; Liver; Liver Neoplasms; Magnetic Resonance Imaging; Multimodal Imaging; Positron Emission Tomography Computed Tomography; Positron-Emission Tomography; Radiopharmaceuticals; Sensitivity and Specificity
PubMed: 38833916
DOI: 10.1016/j.clinimag.2024.110209 -
Cancer Imaging : the Official... Jun 2024This study investigates the value of fluorine 18 ([F])-labeled fibroblast activation protein inhibitor (FAPI) for lymph node (LN) metastases in patients with stage...
BACKGROUND
This study investigates the value of fluorine 18 ([F])-labeled fibroblast activation protein inhibitor (FAPI) for lymph node (LN) metastases in patients with stage I-IIIA non-small cell lung cancer (NSCLC).
METHODS
From November 2021 to October 2022, 53 patients with stage I-IIIA NSCLC who underwent radical resection were prospectively included. [F]-fluorodeoxyglucose (FDG) and [F]FAPI examinations were performed within one week. LN staging was validated using surgical and pathological findings. [F]FDG and [F]FAPI uptake was compared using the Wilcoxon signed-ranks test. Furthermore, the diagnostic value of nodal groups was investigated.
RESULTS
In 53 patients (median age, 64 years, range: 31-76 years), the specificity of [F]FAPI for detecting LN metastasis was significantly higher than that of [F]FDG (P < 0.001). High LN risk category, greater LN short-axis dimension(≥ 1.0 cm), absence of LN calcification or high-attenuation, and higher LN FDG SUV (≥ 10.1) were risk factors for LN metastasis(P < 0.05). The concurrence of these four risk factors accurately predicted LN metastases (Positive Predictive Value [PPV] 100%), whereas the presence of one to three risk factors was unable to accurately discriminate the nature of LNs (PPV 21.7%). Adding [F]FAPI in this circumstance improved the diagnostic value. LNs with an [F]FAPI SUV<6.2 were diagnosed as benign (Negative Predictive Value 93.8%), and LNs with an [F]FAPI SUV≥6.2 without calcification or high-attenuation were diagnosed as LN metastasis (PPV 87.5%). Ultimately, the integration of [F]FDG and [F]FAPI PET/CT resulted in the highest accuracy for N stage (83.0%) and clinical decision revisions for 29 patients.
CONCLUSION
In patients with stage I-IIIA NSCLC, [F]FAPI contributed additional valuable information to reduce LN diagnostic uncertainties after [F]FDG PET/CT. Integrating [F]FDG and [F]FAPI PET/CT resulted in more precise clinical decisions.
TRIAL REGISTRATION
The Chinese Clinical Trial Registry: ChiCTR2100044944 (Registered: 1 April 2021, https://www.chictr.org.cn/showprojEN.html?proj=123995 ).
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Middle Aged; Male; Female; Lung Neoplasms; Prospective Studies; Fluorodeoxyglucose F18; Aged; Positron Emission Tomography Computed Tomography; Adult; Lymphatic Metastasis; Radiopharmaceuticals; Neoplasm Staging; Lymph Nodes
PubMed: 38831354
DOI: 10.1186/s40644-024-00701-y -
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