bims-mesote 2024-04-21 papers

bims-mesote

Biomed News

on Mesothelioma

Issue of 2024‒04‒21
seven papers selected by
Laura Mannarino, Humanitas Research

Development of Patient and Caregiver Conceptual Models Investigating the Health-Related Quality of Life Impacts of Malignant Pleural Mesothelioma.
Therapeutic Strategies to Improve the Treatment of Pleural Mesothelioma.
Risk factors influencing postoperative pleural empyema in patients with pleural mesothelioma: a retrospective single-Centre analysis.
Circulating SMRP and CA-125 before and after pleurectomy decortication for pleural mesothelioma.
Association Study of Pleural Mesothelioma and Oncogenic Simian Virus 40 in the Crocidolite-Contaminated Area of Dayao County, Yunnan Province, Southwest China.
Diffuse pleural mesotheliomas with genomic near-haploidization: a newly recognized subset with distinct clinical, histologic, and molecular features.
High mobility group box 1 mediates inflammatory responses in malignant peritoneal mesothelioma.

Patient. 2024 Apr 15.

Development of Patient and Caregiver Conceptual Models Investigating the Health-Related Quality of Life Impacts of Malignant Pleural Mesothelioma.

Adam E J Gibson, Waqas Ahmed, Louise Longworth, Bryan Bennett, Melinda Daumont, Liz Darlison.

BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare and usually fatal malignancy frequently linked to occupational asbestos exposures and associated with poor prognosis and considerable humanistic burden. The study aimed to develop conceptual models of the health-related quality of life (HRQoL) impact on patients with and receiving treatment for MPM, and the burden on their caregivers.METHODS: This multi-country study (Australia and United Kingdom) adopted a qualitative methodology to conduct semi-structured, independent interviews with people with MPM (n = 26), current caregivers (n = 20), and caregivers of people who had recently died because of MPM (n = 4). Participants were recruited using a purposive sampling approach and interviews conducted via telephone between January 2021 and January 2022. Transcripts were analysed using thematic analysis and used to construct conceptual models.
RESULTS: Patient analysis yielded four overarching themes: (1) debilitating burden of breathlessness and fatigue; (2) physical mesothelioma symptoms experienced by patients; (3) distress of MPM on the self and family; and (4) treatment is worth 'having a go' despite the potential impact on symptoms. Caregiver analysis yielded five core themes: (1) daily life limited by caregiving duties; (2) emotional well-being and the need for support; (3) the relational role shift to caregiver; (4) time spent providing care negatively impacts work and productivity; and (5) positive aspects and outcomes of caregiving.
CONCLUSIONS: This study highlights the substantial daily and emotional HRQoL impact that MPM symptoms have on patients and caregivers. Both groups reduced work, productivity, and social and leisure activities. There was evidence of positive HRQoL impacts as a result of immunotherapy and radiotherapy, but less for chemotherapy. Caregiver impacts were intensified during the end-of-life period and persisted following patient death. Evident is a need for increased psychological support, information, and advice for caregivers, increased during the end-of-life period.

DOI: https://doi.org/10.1007/s40271-024-00690-x
Curr Med Chem. 2024 Apr 16.

Therapeutic Strategies to Improve the Treatment of Pleural Mesothelioma.

Luca Mirra, Giovanni L Beretta, Daniela Lisini, Angela Marcianti, Eleonora Spampinato, Cristina Corno, Matteo Costantino, Angelo Corsico, Giulia Maria Stella, Paola Perego.

  Pleural mesothelioma is a rare neoplastic disease with aggressive features. Patient survival is poor due to the lack of early symptoms and the absence of effective therapeutic strategies. The development of pleural mesothelioma is mainly associated with asbestos exposure and related chronic inflammation. From a molecular-based perspective, this disease is a heterogeneous tumor lacking actionable alterations. The median overall survival of patients affected by this tumor does not exceed 16 months from diagnosis. Molecular and biochemical approaches have shown that this disease is characterized by resistance to drug-induced apoptosis associated with the activation of cell survival pathways and expression of anti-apoptotic proteins. Thus, there is an urgent need to develop efficient and safe therapeutic strategies. Here, we review the pharmacological options available for the treatment of this disease with specific reference to the antitumor agents used in systemic therapies. In addition, novel pharmacological approaches, such as drug delivery tools, to improve pleural mesothelioma treatment are discussed.

Keywords:  BRCA1-associated protein 1; Pleural mesothelioma; apoptosis; drug resistance; genomic alterations; nanodelivery.; pleural mesothelioma therapeutic approaches

DOI:  https://doi.org/10.2174/0109298673268206240405084558
Eur J Cardiothorac Surg. 2024 Apr 18. pii: ezae137. [Epub ahead of print]

Risk factors influencing postoperative pleural empyema in patients with pleural mesothelioma: a retrospective single-Centre analysis.

Peter Henschke, Laura Guglielmetti, Sven Hillinger, Gian-Marco Monsch, Didier Schneiter, Isabelle Opitz, Olivia Lauk.

  OBJECTIVES: Postoperative empyema is a severe, potentially lethal complication also present, but poorly studied in patients undergoing surgery for pleural mesothelioma. We aimed to analyse which perioperative characteristics might be associated with an increased risk for postoperative empyema.METHODS: From September 1999 to February 2023 a retrospective analysis of consecutive patients undergoing surgery for pleural mesothelioma at the University Hospital of Zurich was performed. Uni- and multivariable logistic regression was used to identify associated risk factors of postoperative empyema after surgery.
RESULTS: 400 PM patients were included in the analysis, of which n = 50 patients developed empyema after surgery (12.5%). Baseline demographics were comparable between patients with (Eyes) and without empyema (Eno). 39% (n = 156) patients underwent extrapleural pneumonectomy, of which 22% (n = 35) developed postoperative pleural empyema; 6% (n = 15) of remaining 244 patients undergoing pleurectomy and decortication (n = 46), extended pleurectomy and decortication (n = 114), partial pleurectomy (n = 54) or explorative thoracotomy (n = 30) resulted in postoperative empyema. In multivariable logistic regression analysis, extrapleural pneumonectomy (odds ratio 2.8, 95% confidence interval 1.5-5.4, p = 0.002) emerged as the only risk factor associated with postoperative empyema when controlled for smoking status. Median overall survival was significantly worse for Eyes (16 months, interquartile range 5-27 months) than for Eno (18 months, interquartile range 8-35 months).
CONCLUSIONS: Patients undergoing extrapleural pneumonectomy had a significantly higher risk of developing postoperative pleural empyema compared to patients undergoing other surgery types. Survival of patients with empyema was significantly shorter. A concern emerged of a possible connection between adjuvant radiotherapy and postoperative empyema.

Keywords:  Extrapleural Pleuropneumonectomy; Macroscopic Complete Resection; Multimodal Therapy; Pleural Mesothelioma; Postoperative Pleural Empyema

DOI:  https://doi.org/10.1093/ejcts/ezae137
Thorac Cancer. 2024 Apr 16.

Circulating SMRP and CA-125 before and after pleurectomy decortication for pleural mesothelioma.

Juuso Paajanen, Ahmed Sadek, William G Richards, Yue Xie, Emanuele Mazzola, Kristina Sidopoulos, John Kuckelman, Ritu R Gill, Raphael Bueno.

  BACKGROUND: Tumor recurrence remains the main barrier to survival after surgery for pleural mesothelioma (PM). Soluble mesothelin-related protein (SMRP) and cancer antigen 125 (CA-125) are established blood-based biomarkers for monitoring PM. We prospectively studied the utility of these biomarkers after pleurectomy decortication (PD).METHODS: Patients who underwent PD and achieved complete macroscopic resection with available preoperative SMRP levels were included. Tumor marker levels were determined within 60 days of three timepoints: (1) preoperation, (2) post-operation, and (3) recurrence.
RESULTS: Of 356 evaluable patients, 276 (78%) had recurrence by the end of follow-up interval. Elevated preoperative SMRP levels were associated with epithelioid histology (p < 0.013), advanced TNM (p < 0.001) stage, and clinical stage (p < 0.001). Preoperative CA-125 levels were not significantly associated with clinical covariates. Neither biomarker was associated with survival or disease-free survival. With respect to nonpleural and nonlymphatic recurrences, mean SMRP levels were elevated in patients with pleural (p = 0.021) and lymph node (p = 0.042) recurrences. CA-125 levels were significantly higher in patients with abdominal (p < 0.001) and lymph node (p = 0.004) recurrences. Among patients with all three timepoints available, we observed an average decrease in SMRP levels by 1.93 nmol/L (p < 0.001) postoperatively and again an average increase at recurrence by 0.79 nmol/L (p < 0.001). There were no significant changes in levels of CA-125 across the study timepoints (p = 0.47).
CONCLUSIONS: Longitudinal changes in SMRP levels corresponded with a radiographic presence of disease in a subset of patients. SMRP surveillance could aid in detection of local recurrences, whereas CA-125 could be helpful in recognizing abdominal recurrences.

Keywords:  CA‐125; SMRP; biomarkers; pleural mesothelioma; pleurectomy decortication

DOI:  https://doi.org/10.1111/1759-7714.15264
Genet Test Mol Biomarkers. 2024 Apr 18.

Association Study of Pleural Mesothelioma and Oncogenic Simian Virus 40 in the Crocidolite-Contaminated Area of Dayao County, Yunnan Province, Southwest China.

Ru-Ai Liu, Bo-Yong Wang, Xin Chen, Yuan-Qian Pu, Jia-Ji Zi, Wen Mei, Ye-Pin Zhang, Lu Qiu, Wei Xiong.

  Background: In Dayao County, Chuxiong Yi Autonomous Prefecture, Yunnan Province, Southwest China, 5% of the surface is scattered with blue asbestos, which has a high incidence of pleural mesothelioma (PMe). Simian virus 40 (SV40) is a small circular double-stranded DNA polyomavirus that can cause malignant transformation of normal cells of various human and animal tissue types and promote tumor growth. In this study, we investigate whether oncogenic SV40 is associated with the occurrence of PMe in the crocidolite-contaminated area of Dayao County, Yunnan Province, Southwest China. Methods: Tumor tissues from 51 patients with PMe (40 of whom had a history of asbestos exposure) and pleural tissues from 12 non-PMe patients (including diseases such as pulmonary maculopathy and pulmonary tuberculosis) were collected. Three pairs of low-contamination risk primers (SVINT, SVfor2, and SVTA1) were used to detect the gene fragment of SV40 large T antigen (T-Ag) by polymerase chain reaction (PCR). The presence of SV40 T-Ag in PMe tumor tissues and PMe cell lines was detected by Western blotting and immunohistochemical staining with SV40-related antibodies (PAb 101 and PAb 416). Results: PCR, Western blotting, and immunohistochemical staining results showed that the Met5A cell line was positive for SV40 and contained the SV40 T-Ag gene and protein. In contrast, the various PMe cell lines NCI-H28, NCI-H2052, and NCI-H2452 were negative for SV40. PCR was negative for all three sets of low-contamination risk primers in 12 non-PMe tissues and 51 PMe tissues. SV40 T-Ag was not detected in 12 non-PMe tissues or 51 PMe tissues by immunohistochemical staining. Conclusion: Our data suggest that the occurrence of PMe in the crocidolite-contaminated area of Yunnan Province may not be related to SV40 infection and that crocidolite exposure may be the main cause of PMe. The Clinical Trial Registration number: 2020-YXLL20.

Keywords:  Dayao County; crocidolite; pleural mesothelioma; simian virus 40

DOI:  https://doi.org/10.1089/gtmb.2023.0532
Clin Cancer Res. 2024 Apr 17.

Diffuse pleural mesotheliomas with genomic near-haploidization: a newly recognized subset with distinct clinical, histologic, and molecular features.

Soo-Ryum Yang, Gowtham Jayakumaran, Jamal Benhamida, Christopher A Febres Aldana, Rachel Fanaroff, Jason Chang, Erika Gedvilaite, Liliana B Villafania, Jennifer L Sauter, Michael Offin, Marjorie G Zauderer, Marc Ladanyi.

PURPOSE: Diffuse pleural mesotheliomas (DPMs) with genomic near-haploidization (GNH) represent a novel subtype first recognized by the TCGA project; however, its clinicopathologic and molecular features remain poorly defined.EXPERIMENTAL DESIGN: We analyzed clinical genomic profiling data from 290 patients with DPM using the MSK-IMPACT assay. Allele-specific copy number analysis was performed using the FACETS algorithm.
RESULTS: 210 patients were evaluable for LOH analysis using FACETS. In this cohort, GNH was detected in 10 cases (4.8%). Compared to non-GNH tumors, GNH DPMs were associated with younger age and less frequent self-reported history of occupational asbestos exposure. Histologically, GNH DPMs were enriched in biphasic subtype (80% vs. 14.5%) and showed abundant tumor infiltrating lymphocytes (TILs). Genomic analysis revealed a higher frequency of TP53 alterations, while SETDB1 mutations were present in nearly all and only in this subset. The clinicopathologic and molecular findings were further validated in a separate cohort. Despite the younger age, patients with GNH DPMs had a shorter overall survival (10.9 vs. 25.4 months, p=0.004); the poor prognostic impact of GNH remained significant after controlling for biphasic histology. Out of three patients with GNH DPMs who received immune checkpoint blockade (ICB), two achieved a clinician assessed partial response.
CONCLUSIONS: GNH defines an aggressive subtype of mainly biphasic DPMs in younger patients with recurrent alterations in SETDB1 and TP53. The enrichment in biphasic histology and TILs, together with our preliminary ICB response data and anecdotal clinical trial data, suggests that further evaluation of immunotherapy may be warranted in this subset.

DOI: https://doi.org/10.1158/1078-0432.CCR-24-0085
Int Immunopharmacol. 2024 Apr 12. pii: S1567-5769(24)00557-5. [Epub ahead of print]133 112039

High mobility group box 1 mediates inflammatory responses in malignant peritoneal mesothelioma.

Lianfen Wang, Xuesong Wang, Ningning Sun, Weili Liu.

  BACKGROUND: Serum high mobility group box 1 (HMGB1) serves as a diagnostic biomarker for malignant peritoneal mesothelioma (MPM) patients, yet its diagnostic significance within MPM tumor tissues remains uncertain. This study aims to elucidate the roles of HMGB1 in MPM.METHODS: HMGB1 expression analysis was conducted in both tumor and adjacent non-cancerous tissues collected from MPM patients. The two-year follow-up of MPM patients commenced from the diagnosis date. Inflammatory cytokine analysis was performed on these tissues, and Pearson correlation coefficient analysis was applied to examine variable relationships. In vitro assays included constructing an HMGB1 knockdown cell line, assessing cell viability, apoptosis, and inflammatory cytokine levels to delineate HMGB1's roles in MPM.
RESULTS: HMGB1 overexpression was observed in MPM tumor tissues, particularly in stages III-IV. Diagnostic implications of HMGB1 for MPM were evident, augmenting its diagnostic value. HMGB1 overexpression correlated with diminished survival rates. Positive correlations existed between inflammatory cytokines and HMGB1 in MPM tumor tissues and cell lines. Suppression of HMGB1 regulated cell growth and apoptosis in MPM cell lines.
CONCLUSION: HMGB1 exhibits diagnostic potential for MPM and modulates inflammatory responses within the disease context.

Keywords:  High mobility group box 1; Inflammatory responses; MSTO-211H cells; Malignant peritoneal mesothelioma; Mesothelioma cells

DOI:  https://doi.org/10.1016/j.intimp.2024.112039