bims-mesote Biomed News
on Mesothelioma
Issue of 2022‒06‒05
ten papers selected by
Laura Mannarino
Humanitas Research
  1. Abemaciclib for malignant pleural mesothelioma - Authors' reply.
  2. Unexplained Pleural Effusion Leads to the Revelation of a Malignant Mesothelioma: A Case Report.
  3. The Evolving Therapeutic Landscape for Malignant Pleural Mesothelioma.
  4. Dysregulation of microRNAs and tRNA-derived ncRNAs in mesothelial and mesothelioma cell lines after asbestiform fiber exposure.
  5. Complete and durable response to crizotinib in a patient with malignant pleural mesothelioma harboring CD74-ROS1 fusion.
  6. Discrimination of Malignant Pleural Mesothelioma Cell Lines Using Amino Acid Metabolomics with HPLC.
  7. Comprehensive genomic and tumour immune profiling reveals potential therapeutic targets in malignant pleural mesothelioma.
  8. Abemaciclib for malignant pleural mesothelioma.
  9. Living beyond expectations: a qualitative study into the experience of long-term survivors with pleural mesothelioma and their carers.
  10. Pleural mesothelioma.
  1. Lancet Oncol. 2022 Jun;pii: S1470-2045(22)00285-6. [Epub ahead of print]23(6): e238
    Abemaciclib for malignant pleural mesothelioma - Authors' reply.
    Dean A Fennell, Nada Nusrat.
      
    DOI:  https://doi.org/10.1016/S1470-2045(22)00285-6
  2. Cureus. 2022 Apr;14(4): e24478
    Unexplained Pleural Effusion Leads to the Revelation of a Malignant Mesothelioma: A Case Report.
    Meriem Rhazari, Othman Moueqqit, Sara Gartini, Sanae El Morabit, Safae Diani, Mohammed Aharmim, Afaf Thouil, Hatim Kouismi, Jamal Eddine El Bourkadi.
      Malignant mesothelioma is a rare and aggressive cancer that usually affects subjects with prior asbestos exposure, a major risk factor that has been widely known as carcinogenic, and its use is now controlled if not banned in many areas of the world. Malignant mesothelioma originates from mesothelial surface cells covering the serous cavities, and the pleura is its most common site. Malignant pleural mesothelioma (MPM) typically presents with pleural effusion and chest wall pain with wide pleural thickening at radiological investigation. Although the histological examination along with immunohistochemistry helps yield the diagnosis, clinicians and experts face many challenges in diagnosing malignant mesothelioma not only due to the rarity of the disease but also due to the similarities that the disease share with other malignancies. Here, we report a case of a 55-year-old male patient with a history of chronic asbestos work exposure for 12 years who initially presented with unexplained pleural effusion and chest wall pain and was lost to follow-up but came back later with a worsening clinical state. This case is specially presented to raise awareness against cases of unexplained pleural effusion and chest pain.
    Keywords:  asbestos; epithelioid mesothelioma; malignant mesothelioma; pleural effusion; tuberculosis
    DOI:  https://doi.org/10.7759/cureus.24478
  3. Curr Oncol Rep. 2022 Jun 03.
    The Evolving Therapeutic Landscape for Malignant Pleural Mesothelioma.
    Nirosha D Perera, Aaron S Mansfield.
      PURPOSE OF REVIEW: For patients with malignant pleural mesothelioma, prognosis is poor with extremely low 5-year survival rates and limited therapeutic options. Here, we review the current treatment landscape for mesothelioma and highlight promising future therapeutic directions.RECENT FINDINGS: Evolving frontline therapeutic options for mesothelioma include VEGF inhibition in combination with chemotherapy and dual immune checkpoint inhibition, with synergisms between the therapies and response prediction via biomarkers also being explored. Evolving experimental treatments for mesothelioma include PARP and ALK inhibitors, dendritic and CAR T-cell therapies, anti-mesothelin vaccines, and oncolytic viral therapies, representing timely advances in the field. The therapeutic landscape for malignant pleural mesothelioma is evolving and preferred treatment in the frontline and later settings will likely evolve with it. However, this does not preclude the evidence for including multi-modal therapies spanning angiogenesis and immune checkpoint inhibitors, and biomarker utilization, in current clinical trials and management.
    Keywords:  CAR T-cell therapy; Genetic targets; Immunotherapy; Malignant pleural mesothelioma; Mesothelioma biomarkers; VEGF inhibition
    DOI:  https://doi.org/10.1007/s11912-022-01302-3
  4. Sci Rep. 2022 Jun 02. 12(1): 9181
    Dysregulation of microRNAs and tRNA-derived ncRNAs in mesothelial and mesothelioma cell lines after asbestiform fiber exposure.
    Veronica Filetti, Alessandro La Ferlita, Antonio Di Maria, Venera Cardile, Adriana C E Graziano, Venerando Rapisarda, Caterina Ledda, Alfredo Pulvirenti, Carla Loreto.
      Experimental evidence demonstrated that fluoro-edenite (FE) can develop chronic respiratory diseases and elicit carcinogenic effects. Environmental exposure to FE fibers is correlated with malignant pleural mesothelioma (MPM). An early diagnosis of MPM, and a comprehensive health monitoring of the patients exposed to FE fibers are two clinical issues that may be solved by the identification of specific biomarkers. We reported the microRNA (miRNA) and transfer RNA-derived non coding RNA (tRNA-derived ncRNA) transcriptome in human normal mesothelial and malignant mesothelioma cell lines exposed or not exposed to several concentration FE fibers. Furthermore, an interactive mesothelioma-based network was derived by using NetME tool. In untreated condition, the expression of miRNAs and tRNA-derived ncRNAs in tumor cells was significantly different with respect to non-tumor samples. Moreover, interesting and significant changes were found after the exposure of both cells lines to FE fibers. The network-based pathway analysis showed several signaling and metabolic pathways potentially involved in the pathogenesis of MPM. From papers analyzed by NetME, it is clear that many miRNAs can positively or negatively influence various pathways involved in MPM. For the first time, the analysis of tRNA-derived ncRNAs molecules in the context of mesothelioma has been made by using in vitro systems. Further studies will be designed to test and validate their diagnostic potential in high-risk individuals' liquid biopsies.
    DOI:  https://doi.org/10.1038/s41598-022-13044-0
  5. J Cancer Res Clin Oncol. 2022 Jun 01.
    Complete and durable response to crizotinib in a patient with malignant pleural mesothelioma harboring CD74-ROS1 fusion.
    Xuehua Xie, Mengxing You, Erhong Meng, Shunyou Wang, Beifang Niu, Weiming Huang.
      Malignant pleural mesothelioma (MPM) is a rare and deadly malignancy with an extremely poor prognosis. The median overall survival (OS) of this disease is 12-18 months. However, the oncogenic driver mutations of MPM are rarely understood, and the targeted therapy for it is still under investigation. In this report, we describe a case of MPM with CD74-ROS1 fusion who obtains complete and durable response after receiving crizotinib. By the time of submission, the progression-free survival (PFS) with crizotinib has been 6.0 years, and the patient has survived for 7.6 years. Currently, he is still in complete remission (CR). To the best of our knowledge, this case represents the first report of CD74-ROS1 fusion identified in MPM. Meanwhile, it is also the first report of complete and long-term response to crizotinib in a patient with MPM positive for CD74-ROS1 fusion. This case report might contribute to the tumorigenesis and targeted therapy of this deadly disease.
    Keywords:  CD74-ROS1 fusion; Crizotinib; Malignant pleural mesothelioma; Targeted therapy
    DOI:  https://doi.org/10.1007/s00432-022-04076-0
  6. Biol Pharm Bull. 2022 ;45(6): 724-729
    Discrimination of Malignant Pleural Mesothelioma Cell Lines Using Amino Acid Metabolomics with HPLC.
    Ryoko Tomita, Nao Nishijo, Tadashi Hayama, Toshihiro Fujioka.
      Malignant pleural mesothelioma (MPM) is a malignancy closely associated with asbestos exposure. Although early diagnosis provides a chance of effective treatment and better prognosis, invasive biopsy and cytological procedure are required for definitive diagnosis. In this study, we developed a method to differentiate between MPM and control cell lines, named "amino acid metabolomics," consisting in the assessment of the balance of their amino acid levels in the cell culture medium. Culture media of MESO-1 (MPM cell line) and Met-5A (control) cells were used in this study to evaluate amino acid levels using HPLC, following the fluorescence derivatization method. The time-dependent changes in amino acid levels were visualized on the score plot following principal component analysis, and the results revealed differential changes in amino acid levels between the two cell culture supernatants. A discriminative model based on linear discriminant analysis could distinguish MPM and control cells.
    Keywords:  HPLC; amino acid metabolomics; discriminative model; fluorescence derivatization; malignant mesothelioma cell line; principal component analysis
    DOI:  https://doi.org/10.1248/bpb.b21-00972
  7. Genome Med. 2022 May 30. 14(1): 58
    Comprehensive genomic and tumour immune profiling reveals potential therapeutic targets in malignant pleural mesothelioma.
    Jenette Creaney, Ann-Marie Patch, Venkateswar Addala, Sophie A Sneddon, Katia Nones, Ian M Dick, Y C Gary Lee, Felicity Newell, Ebony J Rouse, Marjan M Naeini, Olga Kondrashova, Vanessa Lakis, Apostolos Nakas, David Waller, Annabel Sharkey, Pamela Mukhopadhyay, Stephen H Kazakoff, Lambros T Koufariotis, Aimee L Davidson, Priya Ramarao-Milne, Oliver Holmes, Qinying Xu, Conrad Leonard, Scott Wood, Sean M Grimmond, Raphael Bueno, Dean A Fennell, John V Pearson, Bruce W Robinson, Nicola Waddell.
      BACKGROUND: Malignant pleural mesothelioma (MPM) has a poor overall survival with few treatment options. Whole genome sequencing (WGS) combined with the immune features of MPM offers the prospect of identifying changes that could inform future clinical trials.METHODS: We analysed somatic mutations from 229 MPM samples, including previously published data and 58 samples that had undergone WGS within this study. This was combined with RNA-seq analysis to characterize the tumour immune environment.
    RESULTS: The comprehensive genome analysis identified 12 driver genes, including new candidate genes. Whole genome doubling was a frequent event that correlated with shorter survival. Mutational signature analysis revealed SBS5/40 were dominant in 93% of samples, and defects in homologous recombination repair were infrequent in our cohort. The tumour immune environment contained high M2 macrophage infiltrate linked with MMP2, MMP14, TGFB1 and CCL2 expression, representing an immune suppressive environment. The expression of TGFB1 was associated with overall survival. A small subset of samples (less than 10%) had a higher proportion of CD8 T cells and a high cytolytic score, suggesting a 'hot' immune environment independent of the somatic mutations.
    CONCLUSIONS: We propose accounting for genomic and immune microenvironment status may influence therapeutic planning in the future.
    Keywords:  Immunotherapy; Malignant pleural mesothelioma; Mutational signatures; RNA sequencing; Tumour micro-environment; Whole genome sequencing
    DOI:  https://doi.org/10.1186/s13073-022-01060-8
  8. Lancet Oncol. 2022 Jun;pii: S1470-2045(22)00276-5. [Epub ahead of print]23(6): e237
    Abemaciclib for malignant pleural mesothelioma.
    Valerio Nardone, Camillo Porta, Rocco Giannicola, Pierpaolo Correale, Luciano Mutti.
      
    DOI:  https://doi.org/10.1016/S1470-2045(22)00276-5
  9. BMJ Open Respir Res. 2022 May;pii: e001252. [Epub ahead of print]9(1):
    Living beyond expectations: a qualitative study into the experience of long-term survivors with pleural mesothelioma and their carers.
    Matthew Johnson, Peter Allmark, Angela Tod.
      BACKGROUND: Malignant pleural mesothelioma (MPM) is characterised by poor prognosis and limited treatment options. However, a minority of patients can survive well beyond these bleak estimates. Little is known about the specific experiences and needs of long-term survivors and families.STUDY PURPOSE: The study aimed to gain in-depth understanding of the experiences of patients diagnosed with MPM 3 or more years, along with their main carer, and to determine the care and support needs of this group.
    PARTICIPANTS AND SETTING: People diagnosed with MPM 3 or more years were recruited via asbestos and mesothelioma social media and support groups. Potential participants were asked to identify someone who acted as their main carer.
    METHOD: The study employed a cross-sectional qualitative interview design. A topic guide aided a conversational interview style, conducted remotely and recorded. Patient and carer pairs were interviewed jointly when possible, but were given an option for separate interviews if preferred. Fifteen patients, with 14 identifying a main carer, consented to participation.
    ANALYSIS: Recorded interviews were transcribed verbatim, and then anonymised by the interviewer. Framework analysis was used to analyse the data iteratively and to develop final themes.
    FINDINGS: Three themes were developed. Participants 'Living beyond expectations' remained acutely aware that MPM was incurable, but developed a range of coping strategies. Periods of disease stability were punctuated with crises of progression or treatment ending, straining coping. 'Accessing treatment' was important for patients and carers, despite the associated challenges. They were aware options were limited, and actively sought new treatments and clinical trials. 'Support needs' were met by healthcare professionals, voluntary groups and social media networks.
    CONCLUSIONS: Managing patients via regional MPM multidisciplinary teams, facilitating equal access to treatment and trials, could reduce patient and carer burden. Greater awareness and support around crisis points for this group could improve care.
    Keywords:  Mesothelioma
    DOI:  https://doi.org/10.1136/bmjresp-2022-001252
  10. Med Clin (Barc). 2022 May 27. pii: S0025-7753(22)00177-4. [Epub ahead of print]
    Pleural mesothelioma.
    José Manuel Porcel.
      The diagnosis of diffuse pleural mesothelioma requires in most cases a pleural biopsy, performed either under imaging guidance (ultrasound or computed tomography) or thoracoscopy. Loss of BAP1 or MTAP expression (immunohistochemistry) and homozygous deletion of CDKN2A (fluorescence in situ hybridization) are the basic molecular markers for the diagnosis of mesothelioma. The histologic type and patient's performance status are the most important prognostic factors. Pleural effusion can be managed by the insertion of tunneled pleural catheters, either as a stand-alone measure (e.g., patients not amenable to multimodality therapy who have been diagnosed by pleural fluid cytology or image-guided biopsy) or combined with the administration of aerosolized talc during a diagnostic thoracoscopy. Immunotherapy is one of the front-line approaches in inoperable patients, particularly in biphasic or sarcomatous histologic varieties.
    Keywords:  Asbesto; Asbestos; BRCA-1 associated protein 1; Catéter permanente; Derrame pleural maligno; Immunotherapy; Indwelling catheters; Inmunoterapia; Malignant pleural effusion; Mesotelioma; Mesothelioma; Proteína 1 asociada a BRCA1
    DOI:  https://doi.org/10.1016/j.medcli.2022.03.007
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