bims-mesote 2023-05-07 papers

bims-mesote

Biomed News

on Mesothelioma

Issue of 2023–05–07
eight papers selected by
Laura Mannarino, Humanitas Research

Sequential multi-parametric MRI in assessment of the histological subtype and features in the malignant pleural mesothelioma xenografts.
Combination therapy with anti-programmed cell death 1 antibody plus angiokinase inhibitor exerts synergistic antitumor effect against malignant mesothelioma via tumor microenvironment modulation.
Establishment and validation of nomograms to predict survival probability of advanced malignant pleural mesothelioma based on the SEER database and a Chinese medical institution.
An evaluation of the methodological quality of published guidelines for the surgical treatment of pleural mesothelioma.
High Expression of SMO and GLI1 Genes with Poor Prognosis in Malignant Mesothelioma.
Characterizing the distribution of alterations in mesothelioma and their correlation to morphology.
Characteristics of transcription profile, adhesion and migration of SETD2-loss Met-5A mesothelial cells exposed with crocidolite.
Mesothelioma palliative care needs: supporting patients and families with new research-based resources.

Heliyon. 2023 Apr;9(4): e15237

Sequential multi-parametric MRI in assessment of the histological subtype and features in the malignant pleural mesothelioma xenografts.

Zhenghua Zhang, Shasha Shen, Jiyao Ma, Tianfu Qi, Chao Gao, Xiong Hu, Dan Han, Yilong Huang.

   Objective: It is still a challenge to find a noninvasive technique to distinguish the histological subtypes of malignant pleural mesothelioma (MPM) and characterize the development of related histological features. We investigated the potential value of multiparametric MRI in the assessment of the histological subtype and development of histologic features in the MPM xenograft model.
Methods: MPM xenograft models were developed by injecting tumour cells into the right axillary space of nude mice. The T1, T2, R2*, T2*, apparent diffusion coefficient (ADC), true diffusion coefficient (D), pseudo diffusion coefficient (D*), and perfusion fraction (f) at 14 d, 28 d, and 42 d were measured and compared between the epithelial and biphasic MPM. Correlations between multiparametric MRI parameters and histologic features, including necrotic fraction (NF) and microvessel density (MVD), were analysed.
Results: This study found that T2, T2* and IVIM-DWI parameters can reflect the spatial and temporal heterogeneity of MPM. Compared to the epithelial MPM, T2 and T2* were higher and ADC, D, D*, and f were lower in the biphasic MPM (P < 0.05). MRI parameters were different in different stages of epithelial and biphasic MPM. Moderate correlations were found between ADC and tumor volume and NF in the epithelial MPM, and there was a correlation between f and tumor volume and NF and MVD in the two groups.
Conclusion: MRI parameters changed with tumor progression in a xenograft model of MPM. MRI parameters may provide useful biomarkers for evaluating the histological subtype and histological features development of MPM.

Keywords:  Histological subtype; Malignant pleural mesothelioma; Microvessel density; Multiparametric MRI; Necrosis

DOI:  https://doi.org/10.1016/j.heliyon.2023.e15237
Lung Cancer. 2023 Apr 26. pii: S0169-5002(23)00757-2. [Epub ahead of print]180 107219

Combination therapy with anti-programmed cell death 1 antibody plus angiokinase inhibitor exerts synergistic antitumor effect against malignant mesothelioma via tumor microenvironment modulation.

Akio Tada, Toshiyuki Minami, Hidemi Kitai, Yoko Higashiguchi, Mayuko Tokuda, Tomoki Higashiyama, Yoshiki Negi, Daisuke Horio, Yasuhiro Nakajima, Taiichiro Otsuki, Koji Mikami, Ryo Takahashi, Akifumi Nakamura, Kazuhiro Kitajima, Masaki Ohmuraya, Kozo Kuribayashi, Takashi Kijima.

  Malignant pleural mesothelioma (MPM) is an asbestos-related fatal malignant neoplasm. Although there has been no reliable chemotherapeutic regimen other than combination therapy of cisplatin and pemetrexed for two decades, combination of ipilimumab plus nivolumab brought about a better outcome in patients with MPM. Thus, cancer immunotherapy using immune checkpoint inhibitor (ICI) is expected to play a central role in the treatment of MPM. To maximize the antitumor effect of ICI, we evaluated whether nintedanib, an antiangiogenic agent, could augment the antitumor effect of anti-programmed cell death 1 (PD-1) antibody (Ab). Although nintedanib could not inhibit the proliferation of mesothelioma cells in vitro, it significantly suppressed the growth of mesothelioma allografts in mice. Moreover, combination therapy with anti-PD-1 Ab plus nintedanib reduced tumor burden more dramatically compared with nintedanib monotherapy via inducing remarkable necrosis in MPM allografts. Nintedanib did not promote the infiltration of CD8+ T cells within the tumor when used alone or in combination with anti-PD-1 Ab but it independently decreased the infiltration of tumor-associated macrophages (TAMs). Moreover, immunohistochemical analysis and ex vivo study using bone marrow-derived macrophages (BMDMs) showed that nintedanib could polarize TAMs from M2 to M1 phenotype. These results indicated that nintedanib had a potential to suppress protumor activity of TAMs both numerically and functionally. On the other hand, ex vivo study revealed that nintedanib upregulated the expression of PD-1 and PD-ligand 1 (PD-L1) in BMDMs and mesothelioma cells, respectively, and exhibited the impairment of phagocytic activity of BMDMs against mesothelioma cells. Co-administration of anti-PD-1 Ab may reactivate phagocytic activity of BMDMs by disrupting nintedanib-induced immunosuppressive signal via binding between PD-1 on BMDMs and PD-L1 on mesothelioma cells. Collectively, combination therapy of anti-PD-1 Ab plus nintedanib enhances the antitumor activity compared with respective monotherapy and can become a novel therapeutic option for patients with MPM.

Keywords:  Angiokinase inhibitor; Immune checkpoint inhibitor; Malignant pleural mesothelioma; Nintedanib; Tumor-associated macrophage; anti-PD-1 Ab

DOI:  https://doi.org/10.1016/j.lungcan.2023.107219
Front Endocrinol (Lausanne). 2023 ;14 1139222

Establishment and validation of nomograms to predict survival probability of advanced malignant pleural mesothelioma based on the SEER database and a Chinese medical institution.

Xuemei Zhang, Lele Chang, Yingying Zhu, Yuxin Mao, Tao Zhang, Qian Zhang, Chunbo Wang.

   Objective: The purpose of this study was to build nomograms for predicting the survival of individual advanced pleural mesothelioma (MPM) patients using the Surveillance, Epidemiology, and End Results (SEER) database.
Methods: The 1251 patients enrolled from the SEER database were randomized (in a 7:3 ratio) to a training cohort and an internal validation cohort. Eighty patients were enrolled from the Harbin Medical University Cancer Hospital as the external validation cohort. Nomograms were constructed from variables screened by univariate or multivariate Cox regression analyses and evaluated by consistency indices (C-index), calibration plots, and receiver operating characteristic (ROC) curves. Patients from the SEER database who received chemotherapy alone and chemoradiotherapy were statistically paired using propensity score matching of the two groups and performed subgroup analysis in the screened variables.
Results: The nomograms are well-structured and well-validated prognostic maps constructed from four variables: gender, histology, AJCC stage, and treatment. All individuals were allocated into high-risk versus low-risk groups based on the median risk score of the training cohort, with the high-risk group having worse OS and CSS in all three cohorts (P<0.05). The outcomes of the subgroup analysis indicated that the advanced MPM patients receiving chemotherapy with or without local radiotherapy do not affect OS or CSS.
Conclusion: The accurate nomograms to predict the survival of patients with advanced MPM were built and validated based on an analysis of the SEER database with an external validation cohort. The study suggests that the additional local radiotherapy to chemotherapy does not increase the survival benefit of patients.

Keywords:  Nomograms; Radiotherapy; SEER database; advanced malignant pleural mesothelioma; prognosis

DOI:  https://doi.org/10.3389/fendo.2023.1139222
Eur J Cancer Prev. 2023 May 03.

An evaluation of the methodological quality of published guidelines for the surgical treatment of pleural mesothelioma.

Luca Bertolaccini, Claudia Bardoni, Gabriele Maffeis, Shehab Mohamed, Elena Prisciandaro, Cristina Diotti, Monica Casiraghi, Francesco Petrella, Lorenzo Spaggiari.

BACKGROUND: To benchmark their quality, a project was designed to analyze the methodology of previous guidelines and recommendations for malignant pleural mesothelioma projects.
METHODS: A narrative literature search was conducted, and each guideline was evaluated using the Appraisal of Guidelines for Research and Evaluation (AGREE) II tool and rated on a seven-point scale for its many items and domains.
RESULTS: Six guidelines that met the inclusion requirements were evaluated. Due to greater development rigor and editorial independence, the engagement of scientific societies was associated with an improvement in methodological quality.
CONCLUSION: According to the standards of AGREE II, the methodological quality of earlier guidelines was relatively low. Nonetheless, two previously published guidelines could serve as a template for the establishment of the most effective methodological quality guidelines.

DOI: https://doi.org/10.1097/CEJ.0000000000000810
Biomed Res Int. 2023 ;2023 6575194

High Expression of SMO and GLI1 Genes with Poor Prognosis in Malignant Mesothelioma.

Guan-Ying Ma, Shuai Shi, Yin-Zhou Sang, Ping Wang, Zhi-Gang Zhang.

Background: To investigate the value of SMO and GLI1 genes in the hedgehog pathway in malignant mesothelioma specimens. Further study on the expression and prognosis of SMO and GLI1 in malignant mesothelioma tissues and the relationship between the two and the molecular mechanisms of mesothelioma immunity and to further investigate the prognostic value of mesothelioma expression.
Materials and Methods: Immunohistochemistry and RT-qPCR were applied to detect the expression of SMO and GLI1 proteins and mRNA in biopsy specimens and plasma cavity effusion specimens from malignant mesothelioma (n = 130) and benign mesothelial tissues (n = 50) and to analyze the clinicopathological significance and survival risk factors of SMO and GLI1 protein expression in mesothelioma. The mechanisms of mesothelioma cell expression and immune cell infiltration were investigated using bioinformatics methods.
Results: SMO and GLI1 in mesothelioma tissues detected high concordance between the diagnostic results of mesothelioma biopsy specimens and plasma cavity effusion specimens. The expression levels of SMO and GLI1 protein and mRNA in mesothelioma tissues were higher than those in benign mesothelioma tissues. The expression levels of SMO and GLI1 protein were correlated with the age, site, and asbestos exposure history of patients with mesothelioma. The expression levels of SMO and GLI1 protein were correlated with the expressions of ki67 and p53 (P < 0.05). SMO and GLI1 gene expression levels were negatively correlated with good prognosis in mesothelioma patients (P < 0.05). Cox proportional risk model indicated that protein expressions of invasion, lymph node metastasis, distant metastasis, staging, and genes were independent prognostic factors of mesothelioma. The GEPIA database showed the overall survival rate and the disease-free survival rate of mesothelioma patients in the high SMO and GLI1 expression groups; the UALCAN database analysis showed lower SMO expression levels in mesothelioma patients with more pronounced TP53 mutations (P = 0.001); GLI1 gene expression levels were strongly correlated with lymph node metastasis in mesothelioma patients (P = 0.009). Timer database analysis showed that the mechanism of immune cell infiltration was closely related to SMO and GLI1 expression. The degree of immune cell infiltration was strongly correlated with the prognosis of mesothelioma patients (P < 0.05).
Conclusion: The expression levels of both SMO and GLI1 proteins were higher than those of normal mesothelial tissues, and the mRNA expression levels also changed in the same direction. SMO and GLI1 gene expressions in mesothelioma were negatively correlated with age, site of occurrence, and history of asbestos exposure. Positive expression of SMO and GLI1 was negatively correlated with patient survival. The Cox proportional risk model showed that gender, history of asbestos exposure, site of occurrence, SMO, and GLI1 were independent prognostic factors for mesothelioma. The mechanism of immune cell infiltration in mesothelioma is closely related to the gene expression of both and the survival prognosis of mesothelioma patients.

DOI: https://doi.org/10.1155/2023/6575194
Am J Clin Pathol. 2023 May 04. pii: aqad041. [Epub ahead of print]

Characterizing the distribution of alterations in mesothelioma and their correlation to morphology.

Heather I-Hsuan Chen-Yost, Melissa Y Tjota, Guimin Gao, Owen Mitchell, Hedy Kindler, Jeremy Segal, Aliya N Husain, Jeffrey Mueller, Jefree J Schulte.

   OBJECTIVES: Mesothelioma is a lethal disease that arises from the serosal lining of organ cavities. Several recurrent alterations have been observed in pleural and peritoneal -mesotheliomas, including in BAP1, NF2, and CDKN2A. Although specific histopathologic parameters have been correlated with prognosis, it is not as well known whether genetic alterations correlate with histologic findings.
METHODS: We reviewed 131 mesotheliomas that had undergone next-generation sequencing (NGS) at our institutions after pathologic diagnosis. There were 109 epithelioid mesotheliomas, 18 biphasic mesotheliomas, and 4 sarcomatoid mesotheliomas. All our biphasic and sarcomatoid cases arose in the pleura. Of the epithelioid mesotheliomas, 73 were from the pleura and 36 were from the peritoneum. On average, patients were 66 years of age (range, 26-90 years) and predominantly male (92 men, 39 women).
RESULTS: The most common alterations identified were in BAP1, CDKN2A, NF2, and TP53. Twelve mesotheliomas did not show a pathogenic alteration on NGS. For epithelioid mesotheliomas in the pleura, the presence of an alteration in BAP1 correlated with low nuclear grade (P = .04), but no correlation was found in the peritoneum (P = .62). Similarly, there was no correlation between the amount of solid architecture in epithelioid mesotheliomas and any alterations in the pleura (P = .55) or peritoneum (P = .13). For biphasic mesotheliomas, cases with either no alteration detected or with an alteration in BAP1 were more likely to be epithelioid predominant (>50% of the tumor, P = .0001), and biphasic mesotheliomas with other alterations detected and no alteration in BAP1 were more likely to be sarcomatoid predominant (>50% of the tumor, P = .0001).
CONCLUSIONS: This study demonstrates a significant association between morphologic features associated with a better prognosis and an alteration in BAP1.

Keywords:  mesothelioma; molecular; peritoneum; pleura; pulmonary pathology; thoracic pathology

DOI:  https://doi.org/10.1093/ajcp/aqad041
J Appl Toxicol. 2023 May 05.

Characteristics of transcription profile, adhesion and migration of SETD2-loss Met-5A mesothelial cells exposed with crocidolite.

Dan Yang, Chiyun Chen, Hailing Xia, Junqiang Chen, Min Yu.

  Asbestos is fibrous silicate mineral exhibiting biopersistence and carcinogen property and contribute to mesothelioma. Despite the concept of gene-environmental interaction in pathogenesis of mesothelioma, the possible pathophysiological changes of mesothelial cells simultaneously with SETD2 loss and asbestos exposure remains obscure. Herein, CRISPR/Cas9-mediated SETD2 knockout Met-5A mesothelial cells (Met-5ASETD2-KO ) were established and exposed with crocidolite, an amphibole asbestos. Cell viability of Met-5ASETD2-KO appeared to dramatically decrease with ≥ 2.5 μg/cm2 crocidolite exposure as compared to Met-5A, although no cytotoxicity and apoptosis changes of Met-5ASETD2-KO and Met-5A was evident with 1.25 μg/cm2 crocidolite exposure for 48 h. RNA sequencing uncovered top 50 differentially expressed genes (DEGs) between 1.25 μg/cm2 crocidolite exposed Met-5ASETD2-KO (Cro-Met-5ASETD2-KO ) and 1.25 μg/cm2 crocidolite exposed Met-5A (Cro-Met-5A), and ITGA4, THBS2, MYL7, RAC2, CADM1, and CLDN11 appeared to be the primary DEGs involved with adhesion in GO and KEGG analysis. Cro-Met-5ASETD2-KO had strong migration but mild adhesion behavior as compared to Cro-Met-5A. Additionally, crocidolite tended to increase migration of Met-5ASETD2-KO but inhibited migration of Met-5A when compared to their corresponding cells without crocidolite exposure, although no further adhesion property changes was evident for both cells in response to crocidolite. Therefore, crocidolite may affect adhesion-related gene expression and modify adhesion and migration behavior for SETD2-depleted Met-5A, which could provide preliminary insight regarding the potential role of SETD2 in cell behavior of asbestos-related malignant mesothelial cell.

Keywords:  Adhesion; Asbestos; Mesothelial cells; Migration; RNA-seq

DOI:  https://doi.org/10.1002/jat.4493
Br J Community Nurs. 2023 May 02. 28(5): 248-252

Mesothelioma palliative care needs: supporting patients and families with new research-based resources.

Sarah Hargreaves, Clare Gardiner, Angela Tod, Liz Darlison.

   BACKGROUND: Mesothelioma is a rare cancer without cure. Clinical guidelines recommend the timely provision of palliative/supportive care; however, a new study identified barriers to achieving this ambition.
OBJECTIVE: The study aimed to explore palliative care needs and the role of Mesothelioma Clinical Nurse Specialists (MCNSs); and to develop resources to address study findings.
METHODS: The mixed-methods study included a literature review, focus groups, interviews and surveys.
RESULTS: The study highlighted the important role of the MCNSs in palliative care and the need to: address disjointed care; improve support for families; and explain the benefits of palliative care for patients/families. A co-production approach developed an animation for patients/families to demystify palliative care and explain the benefits of early-stage engagement; and an infographic targeted at community and primary care professionals. Recommendations for community nursing practice are described.

Keywords:  Mesothelioma; community nursing; palliative care; patients and families

DOI:  https://doi.org/10.12968/bjcn.2023.28.5.248