scholarly journals Diagnostic and Prognostic Utility of the Extracellular Vesicles Subpopulations Present in Pleural Effusion

Biomolecules ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 1606
Author(s):  
Joman Javadi ◽  
André Görgens ◽  
Hanna Vanky ◽  
Dhanu Gupta ◽  
Anders Hjerpe ◽  
...  
Keyword(s):  
Pleural Effusion ◽  
Extracellular Vesicles ◽  
Early Stage ◽  
Asbestos Exposure ◽  
Soluble Proteins ◽  
Diagnostic Markers ◽  
University Hospital ◽  
Soluble Form ◽  
Matrix Remodeling ◽  
Apoptotic Bodies

Extracellular vesicles (EVs), comprising exosomes, microvesicles, and apoptotic bodies, are released by all cells into the extracellular matrix and body fluids, where they play important roles in intercellular communication and matrix remodeling in various pathological conditions. Malignant pleural mesothelioma (MPM) is a primary tumor of mesothelial origin, predominantly related to asbestos exposure. The detection of MPM at an early stage and distinguishing it from benign conditions and metastatic adenocarcinomas (AD) is sometimes challenging. Pleural effusion is often the first available biological material and an ideal source for characterizing diagnostic and prognostic factors. Specific proteins have previously been identified as diagnostic markers in effusion, but it is not currently known whether these are associated with vesicles or released in soluble form. Here, we study and characterize tumor heterogeneity and extracellular vesicle diversity in pleural effusion as diagnostic or prognostic markers for MPM. We analyzed extracellular vesicles and soluble proteins from 27 pleural effusions, which were collected and processed at the department of pathology and cytology at Karolinska University Hospital, representing three different patient groups, MPM (n = 9), benign (n = 6), and AD (n = 12). The vesicles were fractionated into apoptotic bodies, microvesicles, and exosomes by differential centrifugation and characterized by nanoparticle tracking analysis and Western blotting. Multiplex bead-based flow cytometry analysis showed that exosomal markers were expressed differently on EVs present in different fractions. Further characterization of exosomes by a multiplex immunoassay (Luminex) showed that all soluble proteins studied were also present in exosomes, though the ratio of protein concentration present in supernatant versus exosomes varied. The proportion of Angiopoietin-1 present in exosomes was generally higher in benign compared to malignant samples. The corresponding ratios of Mesothelin, Galectin-1, Osteopontin, and VEGF were higher in MPM effusions compared to those in the benign group. These findings demonstrate that relevant diagnostic markers can be recovered from exosomes.

The emerging roles of extracellular vesicles in ovarian cancer

2020 ◽  
Vol 21 ◽  
Author(s):  
Yin-xue Wang ◽  
Yi-xiang Wang ◽  
Yi-ke Li ◽  
Shi-yan Tu ◽  
Yi-qing Wang
Keyword(s):  
Ovarian Cancer ◽  
Extracellular Vesicles ◽  
Large Scale ◽  
Current Treatment ◽  
Detection Methods ◽  
Drug Resistant ◽  
Apoptotic Bodies ◽  
Biological Mechanisms ◽  
Gynecological Malignancy ◽  
Resistance To Chemotherapy

: Ovarian cancer (OC) is one of the deadliest gynecological malignancy. Epithelial ovarian cancer (EOC) is its most common form. OC has both a poor prognosis and a high mortality rate due to the difficulties of early diagnosis, the limitation of current treatment and resistance to chemotherapy. Extracellular vesicles is a heterogeneous group of cellderived submicron vesicles which can be detected in body fluids, and it can be classified into three main types including exosomes, micro-vesicles, and apoptotic bodies. Cancer cells can produce more EVs than healthy cells. Moreover, the contents of these EVs have been found distinct from each other. It has been considered that EVs shedding from tumor cells may be implicated in clinical applications. Such as a tool for tumor diagnosis, prognosis and potential treatment of certain cancers. In this review, we provide a brief description of EVs in diagnosis, prognosis, treatment, drug-resistant of OC. Cancer-related EVs show powerful influences on tumors by various biological mechanisms. However, the contents mentioned above remain in the laboratory stage and there is a lack of large-scale clinical trials, and the maturity of the purification and detection methods is a constraint. In addition, amplification of oncogenes on ecDNA is remarkably prevalent in cancer, it may be possible that ecDNA can be encapsulated in EVs and thus detected by us. In summary, much more research on EVs needs to be perform to reveal breakthroughs in OC and to accelerate the process of its application on clinic.

scholarly journals SEOM clinical guidelines for the treatment of malignant pleural mesothelioma (2020)

2021 ◽  
Vol 23 (5) ◽  
pp. 980-987 ◽  
Author(s):  
E. Nadal ◽  
J. Bosch-Barrera ◽  
S. Cedrés ◽  
J. Coves ◽  
R. García-Campelo ◽  
...  
Keyword(s):  
Survival Benefit ◽  
Early Stage ◽  
Asbestos Exposure ◽  
Standard Of Care ◽  
Tumor Board ◽  
Pleural Mesothelioma ◽  
Therapeutic Approaches ◽  
Dismal Prognosis ◽  
Line Chemotherapy ◽  
Multidisciplinary Tumor Board

AbstractMesothelioma is a rare and aggressive tumour with dismal prognosis arising in the pleura and associated with asbestos exposure. Its incidence is on the rise worldwide. In selected patients with early-stage MPM, a maximal surgical cytoreduction in combination with additional antitumour treatment may be considered in selected patients assessed by a multidisciplinary tumor board. In patients with unresectable or advanced MPM, chemotherapy with platinum plus pemetrexed is the standard of care. Currently, no standard salvage therapy has been approved yet, but second-line chemotherapy with vinorelbine or gemcitabine is commonly used. Novel therapeutic approaches based on dual immunotherapy or chemotherapy plus immunotherapy demonstrated promising survival benefit and will probably be incorporated in the future.

scholarly journals Asbestos Exposure Level and the Carcinogenic Risk Due to Corrugated Asbestos-Cement Slate Roofs in Korea

2021 ◽  
Vol 18 (13) ◽  
pp. 6925
Author(s):  
Eun-Soo Lee ◽  
Young-Ki Kim
Keyword(s):  
Asbestos Exposure ◽  
Health Impact ◽  
Pooled Analysis ◽  
Carcinogenic Risk ◽  
University Hospital ◽  
Exposure Level ◽  
Lifetime Cancer Risk ◽  
Indoor Exposure ◽  
Asbestos Cement ◽  
Environmental Causes

Asbestos-cement slate roofs are one of the most common environmental causes of asbestos exposure. However, few studies have examined residential asbestos-cement slate-related exposure and its effects on human health. This study was performed to evaluate cumulative asbestos exposure levels and to calculate the Excess Lifetime Cancer Risk (ELCR) of residents of asbestos-cement slate-roofed houses. We reviewed previous Korean literature to estimate the concentration of airborne asbestos from asbestos-cement slate roofed buildings. Finally, eight studies were selected, and a pooled analysis was performed. The results derived from the pooled analysis were combined with the data from a health impact survey conducted from 2009 to 2016 at the Environmental Health Center for Asbestos (EHCA) of the Yangsan Pusan National University Hospital, and a carcinogenic risk assessment was performed. As a result, the representative value of the indoor exposure concentration related to asbestos-cement slate was found to be 0.0032 f/cc on average, and the representative value of the exposure related to occupational asbestos-cement slate dismantling and demolition was found to be 0.0034 f/cc. In addition, the ELCR of asbestos-cement slate related indoor exposure and occupational dismantling and demolition was found to be of medium risk, and the ELCR of residential dismantling and demolition of asbestos-cement slate was less than 10−6, indicating that the risk was low. Since there is no threshold for carcinogenicity related to asbestos, this should not be ignored even if the risk appears low, and it would be reasonable to calculate the carcinogenic risk based on total lifetime exposure. More studies on asbestos exposure scenarios and the scope of similar exposure groups through additional data collection and further analysis of risk are needed.

scholarly journals Contagion Management at the Méditerranée Infection University Hospital Institute

2021 ◽  
Vol 10 (12) ◽  
pp. 2627
Author(s):  
Pierre-Edouard Fournier ◽  
Sophie Edouard ◽  
Nathalie Wurtz ◽  
Justine Raclot ◽  
Marion Bechet ◽  
...  
Keyword(s):  
Infectious Disease ◽  
Early Diagnosis ◽  
Personal Protective Equipment ◽  
Early Stage ◽  
Point Of Care ◽  
University Hospital ◽  
Protective Equipment ◽  
Monitoring Point ◽  
Epidemiological Monitoring ◽  
Wide Range

The Méditerranée Infection University Hospital Institute (IHU) is located in a recent building, which includes experts on a wide range of infectious disease. The IHU strategy is to develop innovative tools, including epidemiological monitoring, point-of-care laboratories, and the ability to mass screen the population. In this study, we review the strategy and guidelines proposed by the IHU and its application to the COVID-19 pandemic and summarise the various challenges it raises. Early diagnosis enables contagious patients to be isolated and treatment to be initiated at an early stage to reduce the microbial load and contagiousness. In the context of the COVID-19 pandemic, we had to deal with a shortage of personal protective equipment and reagents and a massive influx of patients. Between 27 January 2020 and 5 January 2021, 434,925 nasopharyngeal samples were tested for the presence of SARS-CoV-2. Of them, 12,055 patients with COVID-19 were followed up in our out-patient clinic, and 1888 patients were hospitalised in the Institute. By constantly adapting our strategy to the ongoing situation, the IHU has succeeded in expanding and upgrading its equipment and improving circuits and flows to better manage infected patients.

Development of extracellular vesicles-based classifier for detection of early-stage bladder, ovarian, and pancreatic cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3048-3048
Author(s):  
Juan Pablo Hinestrosa ◽  
Razelle Kurzrock ◽  
Jean Lewis ◽  
Nick Schork ◽  
Ashish M. Kamat ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Confidence Interval ◽  
Extracellular Vesicles ◽  
Metastatic Disease ◽  
Cancer Detection ◽  
Early Stage ◽  
Expression Patterns ◽  
Stepwise Logistic Regression ◽  
Liquid Biopsies ◽  
Cancer Early Detection

3048 Background: Many cancers are lethal because they present with metastatic disease. Because localized/resectable tumors produce vague symptoms, diagnosis is delayed. In pancreatic cancer, only ̃10% of patients survive five years, and it will soon become the second leading cause of cancer-related deaths in the USA. For patients with metastatic disease, the 2- and 5-year survival is < 10% and ̃3%, respectively. For the few patients with local disease, 5-year survival is ̃40%. Many other cancers have comparable differences between early- and late-stage disease. It is apparent a diagnostic assay for early-stage cancers would transform the field by minimizing the need for aggressive surgeries and other harsh interventions, and by its potential to increase survival. Identifying cancer-specific aberrations in blood-based “liquid” biopsies offers a prospect for a non-invasive cancer detection tool. In the bloodstream, there are extracellular vesicles (EVs) with cargoes including membrane and cytosolic proteins, as well as RNA and lipids derived from their parent cells. Methods: We used an alternating current electrokinetics (ACE) microarray to isolate EVs from the plasma of stage I and II bladder (N = 48), ovarian (N = 42), and pancreatic cancer patients (N = 44), and healthy volunteers (N = 110). EVs were analyzed using multiplex protein immunoassays for 54 cancer-related proteins. EV protein expression patterns were analyzed using stepwise logistic regression followed by a split between training and test sets (67%/33% respectively). This process enabled biomarker selection and generation of a classifier to discriminate between cancer and healthy donors. Results: The EV protein-based classifier had an overall area under curve (AUC) of 0.95 with a sensitivity of 71.2% (69.4% – 73.0%, at 95% confidence interval) at > 99% specificity. The classifier’s performance for the pancreatic cancer cohort was very strong, with overall sensitivity of 95.7% (94.6% – 96.9%, at 95% confidence interval) at > 99% specificity. Conclusions: EV-associated proteins may enable early cancer detection where surgical resection is most likely to improve outcomes. The classifier’s performance for the initial three cancers studied showed encouraging results. Future efforts will include examining additional cancer types and evaluating the classifier performance using samples from donors with related benign conditions with the aim of a pan-cancer early detection assay.

scholarly journals Extracellular Vesicles and Matrix Remodeling Enzymes: The Emerging Roles in Extracellular Matrix Remodeling, Progression of Diseases and Tissue Repair

Cells ◽  
2018 ◽  
Vol 7 (10) ◽  
pp. 167 ◽  
Author(s):  
Muhammad Nawaz ◽  
Neelam Shah ◽  
Bruna Zanetti ◽  
Marco Maugeri ◽  
Renata Silvestre ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Extracellular Vesicles ◽  
Tissue Repair ◽  
Metabolic Diseases ◽  
Bioactive Molecules ◽  
Tissue Inhibitors Of Metalloproteinases ◽  
Matrix Remodeling ◽  
Pathological Conditions ◽  
Potential Applications ◽  
Non Coding Rnas

Extracellular vesicles (EVs) are membrane enclosed micro- and nano-sized vesicles that are secreted from almost every species, ranging from prokaryotes to eukaryotes, and from almost every cell type studied so far. EVs contain repertoire of bioactive molecules such as proteins (including enzymes and transcriptional factors), lipids, carbohydrates and nucleic acids including DNA, coding and non-coding RNAs. The secreted EVs are taken up by neighboring cells where they release their content in recipient cells, or can sail through body fluids to reach distant organs. Since EVs transport bioactive cargo between cells, they have emerged as novel mediators of extra- and intercellular activities in local microenvironment and inter-organ communications distantly. Herein, we review the activities of EV-associated matrix-remodeling enzymes such as matrix metalloproteinases, heparanases, hyaluronidases, aggrecanases, and their regulators such as extracellular matrix metalloproteinase inducers and tissue inhibitors of metalloproteinases as novel means of matrix remodeling in physiological and pathological conditions. We discuss how such EVs act as novel mediators of extracellular matrix degradation to prepare a permissive environment for various pathological conditions such as cancer, cardiovascular diseases, arthritis and metabolic diseases. Additionally, the roles of EV-mediated matrix remodeling in tissue repair and their potential applications as organ therapies have been reviewed. Collectively, this knowledge could benefit the development of new approaches for tissue engineering.

scholarly journals Scalp Metastasis of Mesothelioma

2021 ◽  
Author(s):  
İlkin Yetişkin ◽  
Berna Eren Kömürcüoğlu ◽  
Eylem Yıldırım
Keyword(s):  
Adrenal Gland ◽  
Malignant Mesothelioma ◽  
Malignant Tumor ◽  
Late Stage ◽  
Poor Prognosis ◽  
Early Stage ◽  
Asbestos Exposure ◽  
Distant Metastases ◽  
Rare Neoplasm ◽  
Scalp Metastasis

Mesothelioma is a primary malignant tumor of the mesothelial cells lining the pleura, pericardium and peritoneum, which is frequently seen between the ages of 40-60. Malignant mesothelioma (MM) is a rare neoplasm with a poor prognosis, usually associated with asbestos exposure. It is characterized by aggressive local invasion and metastatic spread. Extrathoracic lymphogenous-hematogenous metastases are rare at the time of diagnosis and in the early stage. However, metastases develop in at least half of the cases in the late stage of the disease. After the spread of serous membranes, distant metastases to the bone, adrenal gland, and liver are frequently observed. Skin and scalp metastases are rarely observed. Our case MPM is presented because it is a rare scalp metastasis.

scholarly journals The Fatty Acid and Protein Profiles of Circulating CD81-Positive Small Extracellular Vesicles Are Associated with Disease Stage in Melanoma Patients

Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 4157
Author(s):  
Giovanni Paolino ◽  
Veronica Huber ◽  
Serena Camerini ◽  
Marialuisa Casella ◽  
Alberto Macone ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Extracellular Vesicles ◽  
Ad Hoc ◽  
Early Stage ◽  
Disease Onset ◽  
Protein Composition ◽  
Disease Stage ◽  
Biological Macromolecules ◽  
Healthy Donors ◽  
Melanoma Patients

The early detection of cutaneous melanoma, a potentially lethal cancer with rising incidence, is fundamental to increasing survival and therapeutic adjustment. In stages II–IV especially, additional indications for adjuvant therapy purposes after resection and for treatment of metastatic patients are urgently needed. We investigated whether the fatty acid (FA) and protein compositions of small extracellular vesicles (sEV) derived from the plasma of stage 0–I, II and III–IV melanoma patients (n = 38) could reflect disease stage. The subpopulation of sEV expressing CD81 EV marker (CD81sEV) was captured by an ad hoc immune affinity technique from plasma depleted of large EV. Biological macromolecules were investigated by gas chromatography and mass spectrometry in CD81sEV. A higher content of FA was detectable in patients with respect to healthy donors (HD). Moreover, a higher C18:0/C18:1 ratio, as a marker of cell membrane fluidity, distinguished early (stage 0–I) from late (III–IV) stages’ CD81sEV. Proteomics detected increases in CD14, PON1, PON3 and APOA5 exclusively in stage II CD81sEV, and RAP1B was decreased in stage III–IV CD81sEV, in comparison to HD. Our results suggest that stage dependent alterations in CD81sEV’ FA and protein composition may occur early after disease onset, strengthening the potential of circulating sEV as a source of discriminatory information for early diagnosis, prediction of metastatic behavior and following up of melanoma patients.

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