-
International Journal of Molecular... May 2024One aspect of ovarian tumorigenesis which is still poorly understood is the tumor-stroma interaction, which plays a major role in chemoresistance and tumor progression....
One aspect of ovarian tumorigenesis which is still poorly understood is the tumor-stroma interaction, which plays a major role in chemoresistance and tumor progression. Cancer-associated fibroblasts (CAFs), the most abundant stromal cell type in the tumor microenvironment, influence tumor growth, metabolism, metastasis, and response to therapy, making them attractive targets for anti-cancer treatment. Unraveling the mechanisms involved in CAFs activation and maintenance is therefore crucial for the improvement of therapy efficacy. Here, we report that CAFs phenoconversion relies on the glucose-dependent inhibition of autophagy. We show that ovarian cancer cell-conditioning medium induces a metabolic reprogramming towards the CAF-phenotype that requires the autophagy-dependent glycolytic shift. In fact, 2-deoxy-D-glucose (2DG) strongly hampers such phenoconversion and, most importantly, induces the phenoreversion of CAFs into quiescent fibroblasts. Moreover, pharmacological inhibition (by proline) or autophagy gene knockdown (by siBECN1 or siATG7) promotes, while autophagy induction (by either 2DG or rapamycin) counteracts, the metabolic rewiring induced by the ovarian cancer cell secretome. Notably, the nutraceutical resveratrol (RV), known to inhibit glucose metabolism and to induce autophagy, promotes the phenoreversion of CAFs into normal fibroblasts even in the presence of ovarian cancer cell-conditioning medium. Overall, our data support the view of testing autophagy inducers for targeting the tumor-promoting stroma as an adjuvant strategy to improve therapy success rates, especially for tumors with a highly desmoplastic stroma, like ovarian cancer.
Topics: Humans; Female; Autophagy; Cancer-Associated Fibroblasts; Ovarian Neoplasms; Glucose; Cell Line, Tumor; Tumor Microenvironment; Resveratrol; Culture Media, Conditioned; Deoxyglucose; Glycolysis
PubMed: 38891879
DOI: 10.3390/ijms25115691 -
BMC Pulmonary Medicine Jun 2024The diagnostic complexities that arise in radiographic distinction between ectopic pleural thymoma and other thoracic neoplasms are substantial, with instances of...
BACKGROUND
The diagnostic complexities that arise in radiographic distinction between ectopic pleural thymoma and other thoracic neoplasms are substantial, with instances of co-occurring T-cell lymphocytosis and osseous metastasis being exceedingly rare.
CASE PRESENTATION
A 51-year-old woman was admitted to our hospital with dyspnea and chest pain. Upon imaging examination, she was found to have diffuse and nodular pleural thickening on the left side, collapse of the left lung and a compression in the second thoracic vertebrae. All lesions showed significant F-FDG uptake on F-FDG PET/CT examination. Furthermore, she exhibited T-cell lymphocytosis in her peripheral blood, lymph nodes, and bone marrow. After ruling out malignant pleural mesothelioma (MPM), lung cancer with pleural metastasis, and T-cell lymphoma, the definitive diagnosis asserted was ectopic pleural thymoma with T-cell lymphocytosis and bone metastasis.
CONCLUSION
Physicians need to expand their knowledge of the imaging features of ectopic pleural thymoma. Cases with T-cell lymphocytosis may exhibit increased aggressiveness and prone to bone metastasis.
Topics: Humans; Female; Middle Aged; Thymoma; Lymphocytosis; Pleural Neoplasms; Bone Neoplasms; Positron Emission Tomography Computed Tomography; Thymus Neoplasms; T-Lymphocytes; Fluorodeoxyglucose F18; Diagnosis, Differential; Pleura
PubMed: 38877486
DOI: 10.1186/s12890-024-03090-x -
Science Advances Jun 2024In vivo molecular imaging tools are crucially important for elucidating how cells move through complex biological systems; however, achieving single-cell sensitivity...
In vivo molecular imaging tools are crucially important for elucidating how cells move through complex biological systems; however, achieving single-cell sensitivity over the entire body remains challenging. Here, we report a highly sensitive and multiplexed approach for tracking upward of 20 single cells simultaneously in the same subject using positron emission tomography (PET). The method relies on a statistical tracking algorithm (PEPT-EM) to achieve a sensitivity of 4 becquerel per cell and a streamlined workflow to reliably label single cells with over 50 becquerel per cell of F-fluorodeoxyglucose (FDG). To demonstrate the potential of the method, we tracked the fate of more than 70 melanoma cells after intracardiac injection and found they primarily arrested in the small capillaries of the pulmonary, musculoskeletal, and digestive organ systems. This study bolsters the evolving potential of PET in offering unmatched insights into the earliest phases of cell trafficking in physiological and pathological processes and in cell-based therapies.
Topics: Positron Emission Tomography Computed Tomography; Animals; Single-Cell Analysis; Cell Tracking; Whole Body Imaging; Mice; Humans; Fluorodeoxyglucose F18; Cell Line, Tumor; Algorithms; Melanoma
PubMed: 38875333
DOI: 10.1126/sciadv.adk5747 -
Tuberkuloz Ve Toraks Jun 2024Tuberculosis (TB) is an airborne infectious disease caused by Mycobacterium tuberculosis (MTB). Although it typically affects the lungs (pulmonary TB), one-fifth of TB...
Tuberculosis (TB) is an airborne infectious disease caused by Mycobacterium tuberculosis (MTB). Although it typically affects the lungs (pulmonary TB), one-fifth of TB cases present as extrapulmonary TB. The diagnosis of extrapulmonary TB is often overlooked due to its atypical clinical and radiological manifestations. Differentiating TB from neoplastic conditions poses significant challenges. A 33-year-old female patient was admitted to the emergency clinic with shortness of breath, cough, and abdominal pain. Postero-anterior chest X-ray revealed massive pleural effusion leading to mediastinal shift. With a preliminary diagnosis of malignant pleural effusion, a pleural catheter was inserted, and the patient was referred for a positron emission tomography (PET/CT) to assess the primary site and the optimal location for a biopsy. The PET/CT revealed asymmetric soft tissue thickening on the left side of the nasopharynx, and increased fluorodeoxyglucose (FDG) uptake in the left cervical lymph nodes raised suspicion regarding primary nasopharyngeal cancer. Additionally, there was an increased FDG uptake observed in the mass lesion located in the right upper lobe, mediastinal lymph nodes, pleural surfaces in the left hemithorax, perihepatic areas, and peritoneum, indicating diffuse metastatic disease. Tuberculosis diagnosis was confirmed through biopsies demonstrating granulomatous inflammation in the lung and nasopharynx, along with culturing MTB from pleural effusion. Positron emission tomography played a crucial role in identifying sites of TB involvement. Despite its rarity, healthcare professionals should consider nasopharyngeal TB as a potential diagnosis when evaluating nasopharyngeal masses.
Topics: Humans; Female; Adult; Diagnosis, Differential; Positron Emission Tomography Computed Tomography; Tuberculosis; Fluorodeoxyglucose F18; Neoplasm Metastasis
PubMed: 38869209
DOI: 10.5578/tt.202402915 -
Cancer Imaging : the Official... Jun 2024Neuroblastoma (NB) is a highly heterogeneous tumor, and more than half of newly diagnosed NB are associated with extensive metastases. Accurately characterizing the...
BACKGROUND
Neuroblastoma (NB) is a highly heterogeneous tumor, and more than half of newly diagnosed NB are associated with extensive metastases. Accurately characterizing the heterogeneity of whole-body tumor lesions remains clinical challenge. This study aims to quantify whole-tumoral metabolic heterogeneity (WMH) derived from whole-body tumor lesions, and investigate the prognostic value of WMH in NB.
METHODS
We retrospectively enrolled 95 newly diagnosed pediatric NB patients in our department. Traditional semi-quantitative PET/CT parameters including the maximum standardized uptake value (SUVmax), the mean standardized uptake value (SUVmean), the peak standardized uptake value (SUVpeak), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were measured. These PET/CT parameters were expressed as PSUVmax, PSUVmean, PSUVpeak, PMTV, PTLG for primary tumor, WSUVmax, WSUVmean, WSUVpeak, WMTV, WTLG for whole-body tumor lesions. The metabolic heterogeneity was quantified using the areas under the curve of the cumulative SUV-volume histogram index (AUC-CSH index). Intra-tumoral metabolic heterogeneity (IMH) and WMH were extracted from primary tumor and whole-body tumor lesions, respectively. The outcome endpoints were overall survival (OS) and progression-free survival (PFS). Survival analysis was performed utilizing the univariate and multivariate Cox proportional hazards regression. The optimal cut-off values for metabolic parameters were obtained by receiver operating characteristic curve (ROC).
RESULTS
During follow up, 27 (28.4%) patients died, 21 (22.1%) patients relapsed and 47 (49.5%) patients remained progression-free survival, with a median follow-up of 35.0 months. In survival analysis, WMTV and WTLG were independent indicators of PFS, and WMH was an independent risk factor of PFS and OS. However, IMH only showed association with PFS and OS. In addition to metabolic parameters, the International Neuroblastoma Staging System (INSS) was identified as an independent risk factor for PFS, and neuron-specific enolase (NSE) served as an independent predictor of OS.
CONCLUSION
WMH was an independent risk factor for PFS and OS, suggesting its potential as a novel prognostic marker for newly diagnosed NB patients.
Topics: Humans; Neuroblastoma; Positron Emission Tomography Computed Tomography; Fluorodeoxyglucose F18; Male; Female; Retrospective Studies; Prognosis; Child, Preschool; Child; Infant; Radiopharmaceuticals; Adolescent; Tumor Burden
PubMed: 38863073
DOI: 10.1186/s40644-024-00718-3 -
Journal of Translational Medicine Jun 2024The purpose of the study was to evaluate the expression and function of basic leucine zipper ATF-like transcription factor (BATF) in colorectal cancer (CRC), and its...
PURPOSE
The purpose of the study was to evaluate the expression and function of basic leucine zipper ATF-like transcription factor (BATF) in colorectal cancer (CRC), and its correlation with 2-deoxy-2[F]fluoro-D-glucose (F-FDG) positron emission tomography/computed tomography (PET/CT) parameters.
METHODS
The TIMER database, GEPIA database, TCGA, and GEO database were used to analyze the expression profile of BATF in human cancers. The reverse transcription‑quantitative PCR and western blot analyses were used to evaluate the mRNA level and protein expression in different CRC cell lines. The expression of BATF in SW620 and HCT116 cells was silenced and cell counting kit-8 assays and clonogenic assay were utilized to evaluate the role of BATF in CRC proliferation. The expression of tumor BATF and glucose transporter 1 (GLUT-1) were examined using immunohistochemical tools in 37 CRC patients undergoing preoperative F-FDG PET/CT imaging. The correlation between the PET/CT parameters and immunohistochemical result was evaluated.
RESULTS
In database, BATF was highly expressed in pan-cancer analyses, including CRC, and was associated with poor prognosis in CRC. In vitro, the results showed that knocking down of BATF expression could inhibit the proliferation of SW620 and HCT116 cells. In CRC patients, BATF expression was upregulated in tumor tissues compared with matched para-tumoral tissues, and was related with gender and Ki-67 levels. BATF expression was positively related to GLUT-1 expression and PET/CT parameters, including tumor size, maximum standard uptake value, metabolic tumor volume, and total lesion glycolysis. The multiple logistic analyses showed that SUV was an independent predictor of BATF expression. With 15.96 g/cm as the cutoff, sensitivity was 85.71%, specificity 82.61%, and area-under-the-curve 0.854.
CONCLUSION
BATF may be an oncogene associated with F-FDG PET/CT parameters in CRC. SUV may be an independent predictor of BATF expression.
Topics: Humans; Fluorodeoxyglucose F18; Colorectal Neoplasms; Basic-Leucine Zipper Transcription Factors; Positron Emission Tomography Computed Tomography; Female; Male; Disease Progression; Cell Proliferation; Cell Line, Tumor; Middle Aged; Gene Expression Regulation, Neoplastic; Glucose Transporter Type 1; Aged
PubMed: 38862971
DOI: 10.1186/s12967-024-05367-5 -
Theranostics 2024The availability of non-invasive drug delivery systems capable of efficiently transporting bioactive molecules across the blood-brain barrier to specific cells at the...
The availability of non-invasive drug delivery systems capable of efficiently transporting bioactive molecules across the blood-brain barrier to specific cells at the injury site in the brain is currently limited. Delivering drugs to neurons presents an even more formidable challenge due to their lower numbers and less phagocytic nature compared to other brain cells. Additionally, the diverse types of neurons, each performing specific functions, necessitate precise targeting of those implicated in the disease. Moreover, the complex synthetic design of drug delivery systems often hinders their clinical translation. The production of nanomaterials at an industrial scale with high reproducibility and purity is particularly challenging. However, overcoming this challenge is possible by designing nanomaterials through a straightforward, facile, and easily reproducible synthetic process. In this study, we have developed a third-generation 2-deoxy-glucose functionalized mixed layer dendrimer () utilizing biocompatible and cost-effective materials a highly facile convergent approach, employing copper-catalyzed click chemistry. We further evaluated the systemic neuronal targeting and biodistribution of , and brain delivery of a neuroprotective agent pioglitazone () in a pediatric traumatic brain injury (TBI) model. The exhibits favorable characteristics including high water solubility, biocompatibility, biological stability, nanoscale size, and a substantial number of end groups suitable for drug conjugation. Upon systemic administration in a pediatric mouse model of traumatic brain injury (TBI), the localizes in neurons at the injured brain site, clears rapidly from off-target locations, effectively delivers , ameliorates neuroinflammation, and improves behavioral outcomes. The promising results coupled with a convenient synthetic approach for the construction of makes it a potential nanoplatform for addressing brain diseases.
Topics: Animals; Dendrimers; Neurons; Drug Delivery Systems; Deoxyglucose; Neuroprotective Agents; Mice; Pioglitazone; Blood-Brain Barrier; Brain Injuries, Traumatic; Brain; Brain Diseases; Humans; Disease Models, Animal; Tissue Distribution; Male
PubMed: 38855177
DOI: 10.7150/thno.95476 -
BMC Cancer Jun 2024The axillary lymph-node metastatic burden is closely associated with treatment decisions and prognosis in breast cancer patients. This study aimed to explore the value...
BACKGROUND
The axillary lymph-node metastatic burden is closely associated with treatment decisions and prognosis in breast cancer patients. This study aimed to explore the value of F-fluorodeoxyglucose (F-FDG) positron emission tomography (PET)/computed tomography (CT)-based radiomics in combination with ultrasound and clinical pathological features for predicting axillary lymph-node metastatic burden in breast cancer.
METHODS
A retrospective analysis was conducted and involved 124 patients with pathologically confirmed early-stage breast cancer who had undergone F-FDG PET/CT examination. The ultrasound, PET/CT, and clinical pathological features of all patients were analysed, and radiomic features from PET images were extracted to establish a multi-parameter predictive model.
RESULTS
The ultrasound lymph-node positivity rate and PET lymph-node positivity rate in the high nodal burden group were significantly higher than those in the low nodal burden group (χ = 19.867, p < 0.001; χ = 33.025, p < 0.001). There was a statistically significant difference in the PET-based radiomics score (RS) for predicting axillary lymph-node burden between the high and low lymph-node burden groups. (-1.04 ± 0.41 vs. -1.47 ± 0.41, t = -4.775, p < 0.001). The ultrasound lymph-node positivity (US_LNM) (odds ratio [OR] = 3.264, 95% confidence interval [CI] = 1.022-10.423), PET lymph-node positivity (PET_LNM) (OR = 14.242, 95% CI = 2.960-68.524), and RS (OR = 5.244, 95% CI = 3.16-20.896) are all independent factors associated with high lymph-node burden (p < 0.05). The area under the curve (AUC) of the multi-parameter (MultiP) model was 0.895, which was superior to those of US_LNM, PET_LNM, and RS models (AUC = 0.703, 0.814, 0.773, respectively), with statistically significant differences (Z = 2.888, 3.208, 3.804, respectively; p = 0.004, 0.002, < 0.001, respectively). Decision curve analysis indicated that the MultiP model provided a higher net benefit for all patients.
CONCLUSION
A MultiP model based on PET-based radiomics was able to effectively predict axillary lymph-node metastatic burden in breast cancer.
TRIAL REGISTRATION
This study was registered with ClinicalTrials.gov (registration number: NCT05826197) on May 7, 2023.
Topics: Humans; Female; Breast Neoplasms; Positron Emission Tomography Computed Tomography; Fluorodeoxyglucose F18; Middle Aged; Lymphatic Metastasis; Retrospective Studies; Axilla; Adult; Aged; Lymph Nodes; Radiopharmaceuticals; Prognosis; Neoplasm Staging; Radiomics
PubMed: 38849770
DOI: 10.1186/s12885-024-12476-3 -
BMC Cancer Jun 2024[F]Fluorodeoxyglucose ([F]FDG) positron emission tomography (PET) is recommended during diagnostic work-up for ovarian cancer; however, [F]FDG PET has several inherent...
BACKGROUND
[F]Fluorodeoxyglucose ([F]FDG) positron emission tomography (PET) is recommended during diagnostic work-up for ovarian cancer; however, [F]FDG PET has several inherent limitations. The novel oncologic PET-tracer fibroblast activation protein inhibitor (FAPI) has demonstrated promising results in multiple cancer types, including ovarian cancer, and could overcome the limitations of [F]FDG PET; however, high-quality clinical studies are lacking. The primary objective of the present study is to compare the diagnostic accuracy of [Ga]Ga-FAPI-46 PET/CT and [F]FDG PET/CT in ovarian cancer patients and to investigate how this potential difference impacts staging and patient management.
METHODS AND DESIGN
Fifty consecutive ovarian cancer patients will be recruited from Aalborg University Hospital, Denmark. This study will be a single-center, prospective, exploratory clinical trial that adheres to the standards for reporting diagnostic accuracy studies (STARD). This study will be conducted under continuous Good Clinical Practice monitoring. The eligibility criteria for patients are as follows: (1) biopsy verified newly diagnosed ovarian cancer or a high risk of ovarian cancer and referred for primary staging with [F]FDG PET/CT; and (2) resectable disease, i.e., candidate for primary debulking surgery or neoadjuvant chemotherapy followed by interval debulking surgery. All recruited study subjects will undergo [Ga]Ga-FAPI-46 PET/CT at primary staging, before primary debulking surgery or neoadjuvant chemotherapy (Group A + B), in addition to conventional imaging (including [F]FDG PET/CT). Study subjects in Group B will undergo an additional [Ga]Ga-FAPI-46 PET/CT following neoadjuvant chemotherapy prior to interval debulking surgery. The results of the study-related [Ga]Ga-FAPI-46 PET/CTs will be blinded, and treatment allocation will be based on common clinical practice in accordance with current guidelines. The histopathology of surgical specimens will serve as a reference standard. A recruitment period of 2 years is estimated; the trial is currently recruiting.
DISCUSSION
To our knowledge, this trial represents the largest, most extensive, and most meticulous prospective FAPI PET study conducted in patients with ovarian cancer thus far. This study aims to obtain a reliable estimation of the diagnostic accuracy of [Ga]Ga-FAPI-46 PET/CT, shed light on the clinical importance of [Ga]Ga-FAPI-46 PET/CT, and examine the potential applicability of [Ga]Ga-FAPI-46 PET/CT for evaluating chemotherapy response.
TRIAL REGISTRATION
clinicaltrials.gov: NCT05903807, 2nd June 2023; and euclinicaltrials.eu EU CT Number: 2023-505938-98-00, authorized 11th September 2023.
Topics: Humans; Female; Positron Emission Tomography Computed Tomography; Ovarian Neoplasms; Prospective Studies; Neoplasm Staging; Fluorodeoxyglucose F18; Gallium Radioisotopes; Radiopharmaceuticals; Middle Aged; Adult; Aged; Quinolines
PubMed: 38849741
DOI: 10.1186/s12885-024-12461-w -
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