bims-mesote Biomed News
on Mesothelioma
Issue of 2023–03–19
ten papers selected by
Laura Mannarino, Humanitas Research
  1. Lifting the curtain on molecular differences between malignant pleural mesotheliomas.
  2. A Narrative Review-Management of Malignant Pleural Effusion Related to Malignant Pleural Mesothelioma.
  3. Prognostic factors and the prognostic role of inflammation indices in malignant pleural mesothelioma.
  4. Effects of pharmacological primary cilium disturbance in the context of in vitro 2D and 3D malignant pleura mesothelioma.
  5. TROP2 expression and SN38 antitumor activity in malignant pleural mesothelioma cells provide a rationale for antibody-drug conjugate therapy.
  6. Malignant pleural mesothelioma characteristics and outcomes: A SEER-Medicare analysis.
  7. Enhancing Pt (IV) Complexes Anticancer Activity Upon Encapsulation in Stimuli Responsive Nanocages.
  8. A rare case of primary gastric Burkitt's lymphoma associated with malignant pleural mesothelioma.
  9. Multiomic analysis of malignant pleural mesothelioma identifies molecular axes and specialized tumor profiles driving intertumor heterogeneity.
  10. Mesothelioma patient and carer experience research: A research prioritisation exercise.
  1. Nat Genet. 2023 Mar 16.
    Lifting the curtain on molecular differences between malignant pleural mesotheliomas.
      
    DOI:  https://doi.org/10.1038/s41588-023-01322-0
  2. Heart Lung Circ. 2023 Mar 14. pii: S1443-9506(23)00099-9. [Epub ahead of print]
    A Narrative Review-Management of Malignant Pleural Effusion Related to Malignant Pleural Mesothelioma.
    Maryum Qureshi, Bibhusal Thapa, Sanjeevan Muruganandan.
      Malignant pleural mesothelioma (MPM) is an aggressive, almost universally fatal cancer with limited therapeutic options. Despite efforts, a real breakthrough in treatment and outcomes has been elusive. Pleural effusion with significant breathlessness and pain is the most typical presentation of individuals with MPM. Although thoracentesis provides relief of breathlessness, most such pleural effusions recur rapidly, and a definitive procedure is often required to prevent a recurrence. Unfortunately, the optimal treatment modality for individuals with recurrent MPM-related effusion is unclear, and considerable variation exists in practice. In addition, non-expandable lung is common in pleural effusions due to MPM and makes effective palliation of symptoms more difficult. This review delves into the latest advances in the available management options (both surgical and non-surgical) for dealing with pleural effusion and non-expandable lung related to MPM. We discuss factors that determine the choice of definitive procedures that need to be tailored to the individual patient.
    Keywords:  Malignant pleural effusion; Malignant pleural mesothelioma; Non-expandable lung
    DOI:  https://doi.org/10.1016/j.hlc.2023.02.004
  3. Turk Gogus Kalp Damar Cerrahisi Derg. 2023 Jan;31(1): 105-115
    Prognostic factors and the prognostic role of inflammation indices in malignant pleural mesothelioma.
    Senar Ebinç, Zeynep Oruç, Ziya Kalkan, Oğur Karhan, Zuhat Urakçı, Mehmet Küçüköner, Muhammet Ali Kaplan, Işıkdoğan Abdurrahman.
       Background: In this study, we aimed to investigate the prognostic factors of malignant pleural mesothelioma and the prognostic value of inflammation indices in malignant pleural mesothelioma.
    Methods: Between January 2002 and December 2019, a total of 132 patients (74 males, 58 females; mean age: 55 years; range, 31 to 79 years) diagnosed with malignant pleural mesothelioma were retrospectively analyzed. Patients" demographic data and laboratory results were recorded. The prognostic value of the following five inflammation indices was evaluated: neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, advanced lung cancer inflammation index, C-reactive protein/albumin ratio, and prognostic nutritional index.
    Results: Of all patients, 81% (n=107) were aged 65 or older and 61.4% (n=81) had an epithelioid histology. Of 12 variables examined in the multivariate analysis for their relationship with survival, age ≥65 years, non-epithelioid subtype, and prognostic nutritional index <40 were found to be poor prognostic factors. Based on the score constructed from these factors, the good prognostic group (score 0-1) had a median overall survival of 21 months and a one-year survival rate of 77.9%, while the poor prognostic group (score 2-3) had a median overall survival of nine months and a one-year survival rate of 29.7%.
    Conclusion: Our study results indicate that age ≥65 years, prognostic nutritional index <40, and non-epithelioid histological subtype are poor prognostic factors of malignant pleural mesothelioma.
    Keywords:  Inflammation indices; malignant pleural mesothelioma; prognostic nutritional index; prognostic score
    DOI:  https://doi.org/10.5606/tgkdc.dergisi.2023.23365
  4. Biochem Biophys Res Commun. 2023 Mar 06. pii: S0006-291X(23)00287-5. [Epub ahead of print]654 128-135
    Effects of pharmacological primary cilium disturbance in the context of in vitro 2D and 3D malignant pleura mesothelioma.
    Rajesh M Jagirdar, Eleanna Pitaraki, Ourania S Kotsiou, Erasmia Rouka, Sotirios I Sinis, Charalampos Varsamas, Periklis Marnas, Elpiniki Stergiopoulou, Anastasios Giannou, Chrissi Hatzoglou, Konstantinos I Gourgoulianis, Sotirios G Zarogiannis.
       INTRODUCTION: Primary cilium (PC) is a single non-motile antenna-like organelle composed of a microtubule core axon originating from the mother centriole of the centrosome. The PC is universal in all mammalian cells and protrudes to the extracellular environment receiving mechanochemical cues that it transmits in the cell.
    AIM: To investigate the role of PC in mesothelial malignancy in the context of two-dimensional (2D) and three-dimensional (3D) phenotypes.
    MATERIALS AND METHODS: The effect of pharmacological deciliation [using ammonium sulphate (AS) or chloral hydrate (CH)] and PC elongation [using lithium chloride (LC)] on cell viability, adhesion, and migration (2D cultures) as well as in mesothelial sphere formation, spheroid invasion and collagen gel contraction (3D cultures) was investigated in benign mesothelial MeT-5A cells and in malignant pleural mesothelioma (MPM) cell lines, M14K (epithelioid) and MSTO (biphasic), and primary malignant pleural mesothelioma cells (pMPM).
    RESULTS: Pharmacological deciliation or elongation of the PC significantly affected cell viability, adhesion, migration, spheroid formation, spheroid invasion and collagen gel contraction in MeT-5A, M14K, MSTO cell lines and in pMPM cells compared to controls (no drug treatment).
    CONCLUSIONS: Our findings indicate a pivotal role of the PC in functional phenotypes of benign mesothelial cells and MPM cells.
    Keywords:  3D cell cultures; Cell invasion; Cell migration; Malignant pleural mesothelioma; Primary cilium; Tumor spheroids
    DOI:  https://doi.org/10.1016/j.bbrc.2023.03.011
  5. Lung Cancer. 2023 Mar 08. pii: S0169-5002(23)00088-0. [Epub ahead of print]178 237-246
    TROP2 expression and SN38 antitumor activity in malignant pleural mesothelioma cells provide a rationale for antibody-drug conjugate therapy.
    Luca Hegedüs, Özlem Okumus, Fabian Mairinger, Till Ploenes, Sebastian Reuter, Martin Schuler, Anja Welt, Silvia Vega-Rubin-de-Celis, Dirk Theegarten, Agnes Bankfalvi, Clemens Aigner, Balazs Hegedüs.
       OBJECTIVES: Malignant pleural mesothelioma (MPM) is an aggressive cancer which at large is not amenable to curative surgery. Despite the recent approval of immune checkpoint inhibitor therapy, the response rates and survival following systemic therapy is still limited. Sacituzumab govitecan is an antibody-drug conjugate targeting the topoisomerase I inhibitor SN38 to trophoblast cell-surface antigen 2 (TROP-2)-positive cells. Here we have explored the therapeutic potential of sacituzumab govitecan in MPM models.
    MATERIALS AND METHODS: TROP2 expression was analyzed in a panel of two well established and 15 pleural effusion derived novel lines by RT-QPCR and immunoblotting, TROP2 membrane-localization was studied by flow cytometry and immunohistochemistry. Cultured mesothelial cells and pneumothorax pleura served as controls. The sensitivity of MPM cell lines to irinotecan and SN38 was studied using cell viability, cell cycle, apoptosis and DNA damage assays. Drug sensitivity of cell lines was correlated with RNA expression of DNA repair genes. Drug sensitivity was defined as an IC50 below 5 nM in the cell viability assay.
    RESULTS: TROP2 expression was detected at RNA and protein level in 6 of the 17 MPM cell lines, but not in in cultured mesothelial control cells or in the mesothelial layer of the pleura. TROP2 was detectable on the cell membrane in 5 MPM lines and was present in the nucleus in 6 cell models. Ten of 17 MPM cell lines showed sensitivity to SN38 treatment, among those 4 expressed TROP2. High AURKA RNA expression and high proliferation rate correlated with sensitivity to SN38-induced cell death, DNA damage response, cell cycle arrest and cell death. Sacituzumab govitecan treatment effectively induced cell cycle arrest and cell death in TROP2-positive MPM cells.
    CONCLUSION: TROP2 expression and sensitivity to SN38 in MPM cell lines support biomarker-selected clinical exploration of sacituzumab govitecan in patients with MPM.
    Keywords:  AURKA; Malignant pleural mesothelioma; SN38; Sacituzumab govitecan; TROP2
    DOI:  https://doi.org/10.1016/j.lungcan.2023.03.003
  6. J Surg Oncol. 2023 Mar 18.
    Malignant pleural mesothelioma characteristics and outcomes: A SEER-Medicare analysis.
    Emanuela Taioli, Andrea Wolf, Naomi Alpert, Daniel Rosenthal, Raja Flores.
       BACKGROUND: Pleural mesothelioma is rare cancer linked to asbestos exposure. Previous research has indicated that female individuals have better survival than male individuals, but this has never been examined in the Surveillance, Epidemiology, and End Results (SEER)-Medicare database.
    MATERIALS AND METHODS: Malignant pleural mesothelioma cases diagnosed from 1992 to 2015 were queried from the linked SEER-Medicare database. Multivariable logistic regression was used to assess the clinical and demographic factors associated with sex. A multivariable Cox proportional hazards model and propensity matching methods were used to assess sex differences in overall survival (OS) while accounting for potential confounders.
    RESULTS: Among 4201 patients included in the analysis, 3340 (79.5%) were males and 861 (20.5%) females. Females were significantly older, with more epithelial histology than males were, and had significantly better OS, adjusted for confounders (adjusted hazard ratio, 0.83, 95% confidence interval: 0.76-0.90). Other variables independently associated with improved survival included younger age at diagnosis, having a spouse/domestic partner, epithelial histology, lower comorbidity score, and receipt of surgery or chemotherapy.
    CONCLUSIONS: The study describes sex differences in mesothelioma occurrence, treatment, and survival and is the first to examine SEER-Medicare. It provides directions for future research into potential therapeutic targets.
    Keywords:  rare cancers; sex differences; survival
    DOI:  https://doi.org/10.1002/jso.27243
  7. Adv Healthc Mater. 2023 Mar 12. e2202932
    Enhancing Pt (IV) Complexes Anticancer Activity Upon Encapsulation in Stimuli Responsive Nanocages.
    María Sancho-Albero, Giorgio Facchetti, Nicolò Panini, Marina Meroni, Ezia Bello, Isabella Rimoldi, Massimo Zucchetti, Roberta Frapolli, Luisa De Cola.
      Platinum-based chemotherapy is the first-line treatment for different cancer types and in particular for malignant pleural mesothelioma patients (a tumor histotype with urgent medical needs). Herein we present a strategy to stabilize, transport and intracellular release of a platinumIV (PtIV ) prodrug using a breakable nanocarrier. Its reduction, and therefore activation as anticancer drug, is promoted by the presence of glutathione in neoplastic cells that also causes the destruction of the carrier. The nanocage presents a single internal cavity in which the hydrophobic complex (Pt(dach)Cl2 (OH)2 ), (dach = R,R-diaminocyclohexane) has been encapsulated. We have evaluated the in vitro uptake and the internalization kinetics in cancer model cells and using flow cytometry analysis, demonstrated the successful release and activation of the Pt based drug inside cancer cells. The in vitro findings were confirmed by the in vivo experiments on a mice model obtained by xenografting MPM487, a patient-derived malignant pleural mesothelioma. MPM487 confirmed the well-known resistance of malignant pleural mesothelioma to cisplatin treatment while an interesting 50% reduction of tumor growth was observed when mice were treated with the PtIV , entrapped in the nanocages, at an equivalent dose of platinum complex. This article is protected by copyright. All rights reserved.
    Keywords:  Organosilica; mesothelioma; nanocages; platinum complexes; tumor reduction
    DOI:  https://doi.org/10.1002/adhm.202202932
  8. Ann Ital Chir. 2023 Mar 06. pii: S2239253X23039221. [Epub ahead of print]12
    A rare case of primary gastric Burkitt's lymphoma associated with malignant pleural mesothelioma.
    Erasmo Spaziani, Annalisa Romina Di Filippo, Giampaolo Valle, Martina Spaziani, Piero Francioni, Gianluca Caruso, Giovanni Traumueller Tamagnini, Edoardo Mosciatti, Marcello Picchio, Alessandro De Cesare.
       BACKGROUND: Primary gastric Burkitt lymphoma (PG BL) and malignant pleural mesothelioma (MPM) are rare and aggressive tumors with poor prognosis. HIV and EBV infection have a link in the aetiology of PG BL, while MPM is usually associated with asbestos exposure. Endoluminal bleeding from massive solid tumor, and dyspnea usually due to pleural effusion, are the typical clinical manifestations respectively of PG BL and MPM. In most patients just palliative treatment is indicated.
    CASE REPORT: A caucasian elderly male, negative for the proven risk factors, presenting respiratory failure due to massive left pleural effusion with severe mediastinal shift. Contrast enhanced - Computed Tomography (CE-CT) showed a large mass causing circumferential thickening of the gastric fundus, infiltrating the left diaphragmatic dome and the ipsilateral crus. Macroscopically, on endoscopy the gastric fundus appeared completely occupied by an ulcerated large mass protunding in the gastric lumen. Histopathological examination from biopsy specimens taken during esophagogastroduodenoscopy and thoracoscopy allowed to make diagnosis of PG BL and MPM. The patient first underwent a placement of a chest tube drainage for the pleural effusion and then a thoracoscopic talc insufflation (TTI) in the left hemithorax. A surgical treatment of the gastric lesion was planned, due to the rapid growth and the high risk of bleeding. The patient died because of fatal cardiac arrhythmia, before undergoig abdominal surgery.
    CONCLUSIONS: This report presents an unique case of PG BL associated with MPM and highlights the real challenge for the physicians to identify them in early stage, especially in patients without the proved risk factors. The onset symptoms make it a very singular case, characterized by severe dyspnea up to respiratory failure, due to massive left pleural effusion and contralateral mediastinal fluttering, without an active bleeding from the gastric mass, while CE-CT findings were instead negative for pleural thickening and positive for circumferential thickening of the gastric fundus.
    KEY WORDS: Burkitt Lymphoma, Case Report, Gastric, Pleural Mesothelioma, Pleural Effusion, Respiratory Failure.
  9. Nat Genet. 2023 Mar 16.
    Multiomic analysis of malignant pleural mesothelioma identifies molecular axes and specialized tumor profiles driving intertumor heterogeneity.
    Lise Mangiante, Nicolas Alcala, Alexandra Sexton-Oates, Alex Di Genova, Abel Gonzalez-Perez, Azhar Khandekar, Erik N Bergstrom, Jaehee Kim, Xiran Liu, Ricardo Blazquez-Encinas, Colin Giacobi, Nolwenn Le Stang, Sandrine Boyault, Cyrille Cuenin, Severine Tabone-Eglinger, Francesca Damiola, Catherine Voegele, Maude Ardin, Marie-Cecile Michallet, Lorraine Soudade, Tiffany M Delhomme, Arnaud Poret, Marie Brevet, Marie-Christine Copin, Sophie Giusiano-Courcambeck, Diane Damotte, Cecile Girard, Veronique Hofman, Paul Hofman, Jérôme Mouroux, Charlotte Cohen, Stephanie Lacomme, Julien Mazieres, Vincent Thomas de Montpreville, Corinne Perrin, Gaetane Planchard, Nathalie Rousseau, Isabelle Rouquette, Christine Sagan, Arnaud Scherpereel, Francoise Thivolet, Jean-Michel Vignaud, Didier Jean, Anabelle Gilg Soit Ilg, Robert Olaso, Vincent Meyer, Anne Boland-Auge, Jean-Francois Deleuze, Janine Altmuller, Peter Nuernberg, Alejandro Ibáñez-Costa, Justo P Castaño, Sylvie Lantuejoul, Akram Ghantous, Charles Maussion, Pierre Courtiol, Hector Hernandez-Vargas, Christophe Caux, Nicolas Girard, Nuria Lopez-Bigas, Ludmil B Alexandrov, Françoise Galateau-Salle, Matthieu Foll, Lynnette Fernandez-Cuesta.
      Malignant pleural mesothelioma (MPM) is an aggressive cancer with rising incidence and challenging clinical management. Through a large series of whole-genome sequencing data, integrated with transcriptomic and epigenomic data using multiomics factor analysis, we demonstrate that the current World Health Organization classification only accounts for up to 10% of interpatient molecular differences. Instead, the MESOMICS project paves the way for a morphomolecular classification of MPM based on four dimensions: ploidy, tumor cell morphology, adaptive immune response and CpG island methylator profile. We show that these four dimensions are complementary, capture major interpatient molecular differences and are delimited by extreme phenotypes that-in the case of the interdependent tumor cell morphology and adapted immune response-reflect tumor specialization. These findings unearth the interplay between MPM functional biology and its genomic history, and provide insights into the variations observed in the clinical behavior of patients with MPM.
    DOI:  https://doi.org/10.1038/s41588-023-01321-1
  10. Eur J Oncol Nurs. 2023 Feb 10. pii: S1462-3889(23)00015-7. [Epub ahead of print]63 102281
    Mesothelioma patient and carer experience research: A research prioritisation exercise.
    Bethany Taylor, Angela Tod, Clare Gardiner, Stephanie Ejegi-Memeh, Madeleine Harrison, Virginia Sherborne, Emilie Couchman, Michaela Senek, Holly Bachas Brook, Jennifer Ross, Xueming Zhang.
       OBJECTIVES: Incidence of mesothelioma worldwide is growing and the UK reports the highest global incidence. Mesothelioma is an incurable cancer with a high symptom burden. However, it is under researched when compared to other cancers. The aim of this exercise was to identify unanswered questions about the mesothelioma patient and carer experience in the UK and to prioritise research areas of most importance through consultation with patients, carers and professionals.
    MATERIALS AND METHODS: A virtual Research Prioritisation Exercise was conducted. This involved a review of mesothelioma patient and carer experience literature to identify research gaps and a national online survey to identify and rank research gaps. Following this, a modified consensus method with mesothelioma experts (patients, carers and professionals from healthcare, legal, academic and volunteer organisations) was undertaken to reach a consensus regarding mesothelioma patient and carer experience research priorities.
    RESULTS: Survey responses were received from 150 patients, carers and professionals and 29 research priorities were identified. During consensus meetings, 16 experts refined these into a list of 11 key priorities. The five most urgent priorities were symptom management, receiving a mesothelioma diagnosis, palliative and end of life care, treatment experiences, barriers and facilitators to joined up service provision.
    CONCLUSION: This novel priority setting exercise will shape the national research agenda, contribute knowledge to inform nursing and wider clinical practice and ultimately improve the experiences of mesothelioma patients and carers.
    Keywords:  Caregivers; Clinical nurse specialist; Clinical practice; Consensus; Grey literature; Mesothelioma; Nursing; Patient experience; Research prioritisation; United Kingdom
    DOI:  https://doi.org/10.1016/j.ejon.2023.102281
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