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Biochemical Genetics Feb 2024Malignant pleural mesothelioma (MPM) is a rare and aggressive neoplasm of the pleural tissue that lines the lungs and is mainly associated with long latency from... (Meta-Analysis)
Meta-Analysis
Malignant pleural mesothelioma (MPM) is a rare and aggressive neoplasm of the pleural tissue that lines the lungs and is mainly associated with long latency from asbestos exposure. This tumor has no effective therapeutic opportunities nowadays and has a very low five-year survival rate. In this sense, identifying molecular events that trigger the development and progression of this tumor is highly important to establish new and potentially effective treatments. We conducted a meta-analysis of genome-wide expression studies publicly available at the Gene Expression Omnibus (GEO) and ArrayExpress databases. The differentially expressed genes (DEGs) were identified, and we performed functional enrichment analysis and protein-protein interaction networks (PPINs) to gain insight into the biological mechanisms underlying these genes. Additionally, we constructed survival prediction models for selected DEGs and predicted the minimum drug inhibition concentration of anticancer drugs for MPM. In total, 115 MPM tumor transcriptomes and 26 pleural tissue controls were analyzed. We identified 1046 upregulated DEGs in the MPM samples. Cellular signaling categories in tumor samples were associated with the TNF, PI3K-Akt, and AMPK pathways. The inflammatory response, regulation of cell migration, and regulation of angiogenesis were overrepresented biological processes. Expression of SOX17 and TACC1 were associated with reduced survival rates. This meta-analysis identified a list of DEGs in MPM tumors, cancer-related signaling pathways, and biological processes that were overrepresented in MPM samples. Some therapeutic targets to treat MPM are suggested, and the prognostic potential of key genes is shown.
Topics: Humans; Mesothelioma, Malignant; Mesothelioma; Phosphatidylinositol 3-Kinases; Pleural Neoplasms; Lung Neoplasms
PubMed: 37347449
DOI: 10.1007/s10528-023-10426-5 -
Archivos de Bronconeumologia Jan 2024Thoracic ultrasound (TU) has rapidly gained popularity over the past 10 years. This is in part because ultrasound equipment is available in many settings, more training... (Review)
Review
Thoracic ultrasound (TU) has rapidly gained popularity over the past 10 years. This is in part because ultrasound equipment is available in many settings, more training programmes are educating trainees in this technique, and ultrasound can be done rapidly without exposure to radiation. The aim of this review is to present the most interesting and innovative aspects of the use of TU in the study of thoracic diseases. In pleural diseases, TU has been a real revolution. It helps to differentiate between different types of pleural effusions, guides the performance of pleural biopsies when necessary and is more cost-effective under these conditions, and assists in the decision to remove thoracic drainage after talc pleurodesis. With the advent of COVID19, the use of TU has increased for the study of lung involvement. Nowadays it helps in the diagnosis of pneumonias, tumours and interstitial diseases, and its use is becoming more and more widespread in the Pneumology ward. In recent years, TU guided biopsies have been shown to be highly cost-effective, with other advantages such as the absence of radiation and the possibility of being performed at bedside. The use of contrast in ultrasound to increase the cost-effectiveness of these biopsies is very promising. In the study of the mediastinum and peripheral pulmonary nodules, the introduction of echobronchoscopy has brought about a radical change. It is a fully established technique in the study of lung cancer patients. The introduction of elastography may help to further improve its cost-effectiveness. In critically-ill patients, diaphragmatic ultrasound helps in the assessment of withdrawal of mechanical ventilation, and is now an indispensable tool in the management of these patients. In neuromuscular patients, ultrasound is a good predictor of impaired lung function. Currently, in Neuromuscular Disease Units, TU is an indispensable tool. Ultrasound study of the intercostal musculature is also effective in the study of respiratory function, and is widely used in Respiratory Rehabilitation. In Intermediate Care Units, thoracic ultrasound is indispensable for patient management. In these units there are ultrasound protocols for the management of patients with acute dyspnoea that have proven to be very effective.
Topics: Humans; Pleural Effusion, Malignant; Pleurodesis; Pleural Diseases; Thoracic Diseases; Pleura
PubMed: 37996336
DOI: 10.1016/j.arbres.2023.10.009 -
Journal of Comparative Pathology Nov 2023Malignant mesotheliomas with localized growth are extremely rare in dogs. A 9-year-old male dog presented with a localized tumour that originated from the parietal...
Malignant mesotheliomas with localized growth are extremely rare in dogs. A 9-year-old male dog presented with a localized tumour that originated from the parietal pleura and had polypoid growth in the thoracic cavity. Histological examination revealed that the tumour consisted of tubular formations with scattered cysts and minimal papillary growth pattern. Neoplastic cells were immunopositive for mesothelial markers (calretinin and Wilms' tumour gene 1) and negative for carcinoma markers (thyroid transcription factor 1 and tumour protein 63). The animal was alive with no recurrence or metastasis/dissemination 11 months after surgery. To the best of our knowledge, this is the first report of a localized mesothelioma in a dog without metastasis/dissemination and highlights the value of mesothelial markers for an accurate diagnosis.
Topics: Male; Dogs; Animals; Mesothelioma, Malignant; Mesothelioma; Biomarkers, Tumor; Carcinoma; Cell Proliferation; Diagnosis, Differential; Dog Diseases
PubMed: 37922825
DOI: 10.1016/j.jcpa.2023.09.006 -
Cell Reports Methods Nov 2023Current in vitro and in vivo assays used to study immunotherapeutic interventions lack human immune components that mimic the tumor microenvironment to investigate...
Current in vitro and in vivo assays used to study immunotherapeutic interventions lack human immune components that mimic the tumor microenvironment to investigate drug potency and limitations of efficacy. Herein, we describe an ex vivo pleural effusion culture (ePEC) assay, using malignant pleural-effusion-derived soluble and cellular factors that differentially affected the cytotoxicity of chimeric antigen receptor (CAR) T cells. Following identification of CAR T cell-suppressive factors, blocking of individual factors reveals their contribution to compromising T cell efficacy. ePEC is a human component assay that can be utilized for developing next-generation cell and antibody therapies that counteract immunosuppression.
Topics: Humans; Receptors, Chimeric Antigen; T-Lymphocytes; Immunotherapy, Adoptive; Pleural Effusion, Malignant; Tumor Microenvironment
PubMed: 37875122
DOI: 10.1016/j.crmeth.2023.100622 -
Seminars in Roentgenology Oct 2023
Topics: Humans; Diagnosis, Differential; Pleural Diseases; Tomography, X-Ray Computed; Pleura; Pleural Neoplasms
PubMed: 37973269
DOI: 10.1053/j.ro.2023.06.001 -
BMC Pulmonary Medicine Sep 2023Tuberculous pleural effusion (TPE) and malignant pleural effusion (MPE) may occasionally show similar cytological and biochemical picture including ADA. In such cases,...
BACKGROUND
Tuberculous pleural effusion (TPE) and malignant pleural effusion (MPE) may occasionally show similar cytological and biochemical picture including ADA. In such cases, differentiating TPE and MPE is challenging and needs histopathology of pleural tissue which may involve invasive procedures. The present study aims to evaluate the diagnostic accuracy of pleural fluid ADA to serum CRP (ADA/CRP) ratio to discriminate between tuberculous and malignant pleural effusion. In addition, we investigated whether the ratio ADA/CRP adds diagnostic value to ADA.
METHODS
This cross-sectional study was conducted in the National Institute of Diseases of the Chest and Hospital (NIDCH), Mohakhali, Dhaka, from July 2021 to February 2022 on diagnosed patients of TPE and malignant pleural effusion MPE. A receiver operating characteristic curve (ROC) was constructed for identifying TPE. The added value of the ADA/CRP ratio to ADA was evaluated using the net reclassification improvement (NRI) and integrated discrimination improvement (IDI). A value of p < 0.05 was considered statistically significant for all tests.
RESULTS
Fifty-nine patients were enrolled in this study, of which 31 had TPE, and 28 had MPE. Pleural fluid ADA to serum CRP ratio and pleural fluid ADA level was significantly higher in patients with TPE, but there was no significant difference in serum CRP levels between patients with TPE and MPE. At cut off value of > 1.25, pleural fluid ADA to serum CRP ratio had a sensitivity of 93.8%, specificity of 85.2%, and positive and negative predictive values were 88.2% and 92% respectively, in the diagnosis of TPE and area under ROC curve (AUC) was 0.94. The NRI and IDI analyses revealed added diagnostic value of ADA/CRP to ADA.
CONCLUSION
This study shows that the ADA/CRP ratio improves the diagnostic usefulness of ADA for TPE.
Topics: Humans; C-Reactive Protein; Pleural Effusion, Malignant; Adenosine Deaminase; Cross-Sectional Studies; Bangladesh; Pleural Effusion; Tuberculosis
PubMed: 37715196
DOI: 10.1186/s12890-023-02644-9 -
Lung Cancer (Amsterdam, Netherlands) Aug 2023VEGF/VEGFR autocrine loop is a hallmark of pleural mesothelioma (PM). We thus assayed the prognostic and predictive values of VEGFR-2 [vascular endothelial growth factor...
OBJECTIVES
VEGF/VEGFR autocrine loop is a hallmark of pleural mesothelioma (PM). We thus assayed the prognostic and predictive values of VEGFR-2 [vascular endothelial growth factor receptor 2 or Flk-1] and CD34, a marker of endothelial cells, in samples from patients accrued in the Mesothelioma Avastin Cisplatin Pemetrexed Study ('MAPS', NCT00651456).
MATERIALS AND METHODS
VEGFR2 and CD34 expression were assayed using immunohistochemistry in 333 MAPS patients (74.3%), and their prognostic value was evaluated in terms of overall survival (OS) and progression-free survival (PFS) in univariate and multivariate analyses, before validation by bootstrap methodology.
RESULTS
Positive VEGFR2 or CD34 staining was observed in 234/333 (70.2%) and 322/323 (99.6%) of tested specimens, respectively. VEGFR2 and CD34 staining correlated weakly, yet significantly, with each other (r = 0.36, p < 0.001). High VEGFR2 expression or high CD34 levels were associated with longer OS in PM patients in multivariate analysis (VEGFR2: adjusted [adj.] hazard ratio [HR]: 0.91, 95% confidence interval [CI] [0.88; 0.95], p < 0.001; CD34: adj. HR: 0.86, 95 %CI [0.76; 0.96], p = 0.010), with only high VEGFR2 expression resulting in significantly longer PFS (VEGFR2: adj. HR: 0.96, 95 %CI [0.92; 0.996], p = 0.032). Stability of these results was confirmed using bootstrap procedure. Nevertheless, VEGFR2 expression failed to specifically predict longer survival in bevacizumab-chemotherapy combination trial arm, regardless of whether the VEGFR2 score was combined or not with serum VEGF concentrations.
CONCLUSION
VEGFR2 overexpression independently correlated with longer OS or PFS in PM patients, such biomarker deserving prospective evaluation as stratification variable in future clinical trials.
Topics: Humans; Antineoplastic Combined Chemotherapy Protocols; Endothelial Cells; Lung Neoplasms; Mesothelioma; Mesothelioma, Malignant; Pemetrexed; Pleural Neoplasms; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor Receptor-2
PubMed: 37393757
DOI: 10.1016/j.lungcan.2023.107287 -
Scientific Reports Feb 2024Diagnosis of malignant pleural effusion (MPE) is made by cytological examination of pleural fluid or histological examination of pleural tissue from biopsy....
Diagnosis of malignant pleural effusion (MPE) is made by cytological examination of pleural fluid or histological examination of pleural tissue from biopsy. Unfortunately, detection of malignancy using cytology has an overall sensitivity of 50%, and is dependent upon tumor load, volume of fluid assessed, and cytopathologist experience. The diagnostic yield of pleural fluid cytology is also compromised by low abundance of tumor cells or when morphology is obscured by inflammation or reactive mesothelial cells. A reliable molecular marker that may complement fluid cytology for the diagnosis of malignant pleural effusion is needed. The purpose of this study was to establish a molecular diagnostic approach based on pleural effusion cell-free DNA methylation analysis for the differential diagnosis of malignant pleural effusion and benign pleural effusion. This was a blind, prospective case-control biomarker study. We recruited 104 patients with pleural effusion for the study. We collected pleural fluid from patients with: MPE (n = 48), indeterminate pleural effusion in subjects with known malignancy or IPE (n = 28), and benign PE (n = 28), and performed the Sentinel-MPE liquid biopsy assay. The methylation level of Sentinel-MPE was markedly higher in the MPE samples compared to BPE control samples (p < 0.0001) and the same tendency was observed relative to IPE (p = 0.004). We also noted that the methylation signal was significantly higher in IPE relative to BPE (p < 0.001). We also assessed the diagnostic efficiency of the Sentinel-MPE test by performing receiver operating characteristic analysis (ROC). For the ROC analysis we combined the malignant and indeterminate pleural effusion groups (n = 76) and compared against the benign group (n = 28). The detection sensitivity and specificity of the Sentinel-MPE test was high (AUC = 0.912). The Sentinel-MPE appears to have better performance characteristics than cytology analysis. However, combining Sentinel-MPE with cytology analysis could be an even more effective approach for the diagnosis of MPE. The Sentinel-MPE test can discriminate between BPE and MPE. The Sentinel-MPE liquid biopsy test can detect aberrant DNA in several different tumor types. The Sentinel-MPE test can be a complementary tool to cytology in the diagnosis of MPE.
Topics: Humans; Pleural Effusion, Malignant; Cell-Free Nucleic Acids; DNA Methylation; Biomarkers, Tumor; Pleural Effusion
PubMed: 38316884
DOI: 10.1038/s41598-024-53132-x -
Biochemia Medica Oct 2023Malignant pleural effusion (MPE) and lymph node metastasis (LNM) presence are poor prognostic factors that have importance for cancer patients. The study objective was...
Clinical importance of serum and pleural fluid prominin-1 and hypoxia-inducible factor-1α concentration in the evaluation of lymph node involvement in patients with malignant pleural effusion.
INTRODUCTION
Malignant pleural effusion (MPE) and lymph node metastasis (LNM) presence are poor prognostic factors that have importance for cancer patients. The study objective was to determine whether hypoxia-inducible factor-1α (HIF-1α) and prominin-1 (CD133) in pleural fluid (P) and serum (S) could be used as biomarkers for diagnosis of lymph node involvement in patients with MPE.
MATERIALS AND METHODS
Fifty-six patients with MPE and 30 healthy control subjects were included. Computerized tomography (CT) and positron emission tomography (PET) were used to diagnose pleural effusion. Patients with malignant cells in pleural fluid cytological examination were included in the MPE group. Thirty-five patients with lymph node metastases on CT were included in the LNM-positive MPE group. Serum and pleural fluid HIF-1α and CD-133 concentrations were measured manually enzyme-linked immunosorbent assay (ELISA).
RESULTS
Serum concentrations of HIF-1α and CD133 were higher in MPE patients. It was found that CD133/HIF-1α (S) ratio was higher in the malignant patient group with positive lymph node involvement than in the negative group, while concentrations of HIF-1α (P) were lower. Pleural fluid HIF-1α and CD133/HIF-1α (S) ratio had sufficient performance in diagnosing lymphatic metastases in patients with MPE (AUC = 0.90 and 0.83, respectively).
CONCLUSIONS
In conclusion, serum HIF-1α and CD133 concentrations were higher in patients with MPE, consistent with our hypothesis. Concentrations of HIF-1α (P) and CD133/HIF-1α (S) ratio can be used as biomarkers in diagnosing lymph node involvement in MPE patients, according to this experiment.
Topics: Humans; Pleural Effusion, Malignant; AC133 Antigen; Clinical Relevance; Hypoxia-Inducible Factor 1, alpha Subunit; Biomarkers; Pleural Effusion; Lymph Nodes; Biomarkers, Tumor
PubMed: 37841777
DOI: 10.11613/BM.2023.030701 -
Targeted Oncology Jan 2024Malignant pleural mesothelioma (MPM) is a rare and challenging cancer associated with asbestos fiber exposure, which offers limited treatment options. Historically,... (Review)
Review
Malignant pleural mesothelioma (MPM) is a rare and challenging cancer associated with asbestos fiber exposure, which offers limited treatment options. Historically, platinum-based chemotherapy has been the primary approach, but recent developments have introduced immunotherapy as a promising alternative for the treatment of this disease. Nevertheless, the unique growth patterns and occasionally ambiguous progressive characteristics of MPM make the interpretation of radiological assessments complex. Immunotherapy further complicates matters by introducing unconventional treatment response patterns such as hyperprogression and pseudoprogression. Consequently, there is a growing imperative to integrate the standard RECIST criteria with the mesothelioma-specific mRECIST criteria (version 1.1), as outlined in iRECIST. This comprehensive review is driven by the intent to provide a valuable resource for radiologists and clinicians engaged in the diagnosis, treatment, and monitoring of MPM in the era of immunotherapy. Specifically, the current imaging methods employed for staging and follow-up will be exposed and discussed, with a focus on the technical specificities and the mRECIST 1.1 methodology. Furthermore, we will provide a discussion about major clinical trials related to the use of immunotherapy in MPM patients. Finally, the latest advancements in radiomics, the applications of artificial intelligence in MPM, and their potential impact on clinical practice for prognosis and therapy, are discussed.
Topics: Humans; Mesothelioma, Malignant; Immune Checkpoint Inhibitors; Artificial Intelligence; Pleural Neoplasms; Lung Neoplasms; Combined Modality Therapy
PubMed: 38063957
DOI: 10.1007/s11523-023-01017-w