bims-mesote Biomed News
on Mesothelioma
Issue of 2021–03–07
six papers selected by
Laura Mannarino, Humanitas Research
  1. Prognostic factors for progression-free and overall survival in malignant pleural mesothelioma.
  2. TRAF7 mutations and immunohistochemical study of uterine adenomatoid tumor compared to malignant mesothelioma.
  3. Malignant mesothelioma without asbestos exposure diagnosed during EGFR-TKI treatment of lung adenocarcinoma: A case report.
  4. Investigating the impact of target lesion selection on drug effect evaluation and tumour growth rate determination using tumour growth inhibition models: example of malignant pleural mesothelioma patients treated with cisplatin alone or in combination with pemetrexed.
  5. Inorganic Fiber Lung Burden in Subjects with Occupational and/or Anthropogenic Environmental Asbestos Exposure in Broni (Pavia, Northern Italy): An SEM-EDS Study on Autoptic Samples.
  6. Osteopontin mRNA expression by rat mesothelial cells exposed to multi-walled carbon nanotubes as a potential biomarker of chronic neoplastic transformation in vitro.
  1. Thorac Cancer. 2021 Mar 04.
    Prognostic factors for progression-free and overall survival in malignant pleural mesothelioma.
    Jordi Guzmán-Casta, Sonia Carrasco-CaraChards, Jorge Guzmán-Huesca, Carla Paola Sánchez-Ríos, Rodrigo Riera-Sala, José Fabián Martínez-Herrera, Erika Sagrario Peña-Mirabal, Diana Bonilla-Molina, Jorge Arturo Alatorre-Alexander, Luis Manuel Martínez-Barrera, Jerónimo Rafael Rodríguez-Cid.
       BACKGROUND: Malignant pleural mesothelioma is an infrequent neoplasia with a poor prognosis and the majority of patients already have advanced disease at the time of presentation. Exposure to asbestos is the most important risk factor for malignant pleural mesothelioma. Mesothelioma is a neoplasia with a long preclinical stage that can span from 15 to 40 years.
    METHODS: This was a descriptive, observational, retrospective study of 136 patients with a confirmed diagnosis of mesothelioma, which compared histological subtypes, immunohistochemical biomarkers, concomitant chronic degenerative diseases, tobacco use, age at the time of diagnosis, clinical stage and chemotherapy agents used or other treatments such as radiotherapy and surgery to identify all the factors that impact in the prognosis of overall survival (OS) and progression-free survival (PFS).
    RESULTS: A total of 136 patients were included in the study. In the total study population, 84 patients were male (61.8%) and 52 were female (38.2%). Median PFS was nine months (95% confidence interval [CI]: 8.4-9.5 months) and median OS was 12 months (95% CI: 11.3-12.6). The results indicated that the most determining prognostic factors for OS and PFS were cell differentiation measured by immunohistochemical biomarkers, the treatment chosen, and that RECIST was the most significant in the evaluation of patient response to treatment.
    CONCLUSIONS: Malignant pleural mesothelioma is a cancer with a poor prognosis usually diagnosed at an advanced stage of disease. Our study revealed that the prognostic factors for OS and PS were cell differentiation, the treatment chosen and RECIST.
    Keywords:  Malignant pleural mesothelioma; overall survival; prognostic factors; progression-free survival
    DOI:  https://doi.org/10.1111/1759-7714.13814
  2. Hum Pathol. 2021 Mar 02. pii: S0046-8177(21)00032-0. [Epub ahead of print]
    TRAF7 mutations and immunohistochemical study of uterine adenomatoid tumor compared to malignant mesothelioma.
    Hiroe Itami, Tomomi Fujii, Tokiko Nakai, Maiko Takeda, Yohei Kishi, Fumiaki Taniguchi, Chiyoko Terada, Fumi Okada, Yuji Nitta, Minami Matsuoka, Shoh Sasaki, Sumire Sugimoto, Tomoko Uchiyama, Kohei Morita, Takahiko Kasai, Ryuji Kawaguchi, Chiho Ohbayashi.
      Adenomatoid tumors (ATs) are benign mesothelial tumors with good prognosis and usually occur in female and male genital tracts, including in the uterus. ATs are genetically defined by tumor necrosis factor receptor-associated factor (TRAF) 7 mutations and a high frequency of AT cases show immunosuppression. On the other hand, malignant mesotheliomas (MMs) are malignant mesothelial tumors with very poor prognosis. Genetic alterations in TRAF, MTAP, and BAP1 in ATs derived from the uterus and MMs of pleural or peritoneal origin were compared by gene sequence analysis or immunohistochemical approaches. Formalin-fixed paraffin-embedded tissues derived from patients were used for immunohistochemical staining of L1CAM, BAP1, MTAP, and HEG1 in 51 uterine AT cases, 34 pleural or peritoneal MM cases, and for next-generation sequencing of the TRAF7 gene in 44 AT cases and 21 MM cases. ATs had a significantly higher rate of L1CAM expression than MMs, while MMs had a significantly higher rate of loss of MTAP and BAP1 expression than ATs. There was no difference in the rate of HEG1 expression between the tumor types. Most of the ATs (37/44; 84%) had somatic mutations in TRAF7, none of the MMs did (0/21; 0%). Additionally, a low frequency of AT cases was associated with a history of immunosuppression (9/51; 17.6%). TRAF7 mutation is one of the major factors distinguishing the development of AT from MM, and immunosuppression might not be associated with most AT cases.
    Keywords:  L1CAM; TRAF7; adenomatoid tumor; malignant mesothelioma
    DOI:  https://doi.org/10.1016/j.humpath.2021.02.007
  3. Cancer Treat Res Commun. 2021 Feb 24. pii: S2468-2942(21)00044-7. [Epub ahead of print]27 100345
    Malignant mesothelioma without asbestos exposure diagnosed during EGFR-TKI treatment of lung adenocarcinoma: A case report.
    Xiaomin Niu, Chenglei Zhou, Aiyan Hu, Lingzi Su, Dan Lin, Hui Han, Yan Lu.
      Synchronous malignant mesothelioma (MM) and lung carcinoma are extremely rare in patients without a history of asbestos exposure and poses tremendous difficulties in clinical management. We report a patient without asbestos exposure diagnosed with MM during EGFR-TKI treatment of lung adenocarcinoma (LUAD), who responded to first-line chemotherapy with pemetrexed plus carboplatin and failed to subsequent systemic therapy. Clinicians should be careful about the possibility of MM comorbidity in LUAD patients whose lesions respond differently to EGFR-TKI, even in those without a history of asbestos exposure.
    Keywords:  GFR-TKI resistance; Lung adenocarcinoma; Lung carcinoma; Malignant mesothelioma (mm)
    DOI:  https://doi.org/10.1016/j.ctarc.2021.100345
  4. Eur J Pharm Sci. 2021 Mar 02. pii: S0928-0987(21)00083-X. [Epub ahead of print] 105781
    Investigating the impact of target lesion selection on drug effect evaluation and tumour growth rate determination using tumour growth inhibition models: example of malignant pleural mesothelioma patients treated with cisplatin alone or in combination with pemetrexed.
    Aurélie Lombard, Hitesh Mistry, Sonya C Chapman, Ivelina Gueorguieva, Leon Aarons, Kayode Ogungbenro.
      In the last update of the RECIST criteria in 2009, it was proposed that the number of target lesions to be followed over time for response-to-treatment assessment be reduced from 10 to 5 lesions maximum, with up to 2 per organ. We explored the impact of reducing the number of target lesion on the assessment of drug effect in a randomised phase III clinical trial using a tumour growth inhibition (TGI) model. Tumour size measurements from 441 (out of 456) patients were used to build two datasets for which observations were the sum of longest diameters of all measurable lesions (ALL dataset) or following the RECIST 1.1 recommendations (R1.1 dataset). TGI models incorporating a categorical covariate for treatment group or a pharmacokinetic metric (i.e. dose; simulated area under the curve) were used to describe the longitudinal tumour size kinetics. Drug exposure was not superior to treatment group at describing drug effect. ALL and R1.1 individual estimates of drug effect appeared to be strongly correlated (r2=0.88). Including pharmacokinetic metrics in TGI models should be conducted carefully when no pharmacokinetic samples are available. Reducing the number of target lesion did not seem to compromise the determination of drug effect using TGI models.
    Keywords:  Target lesion selection; chemotherapy; malignant pleural mesothelioma; modelling
    DOI:  https://doi.org/10.1016/j.ejps.2021.105781
  5. Int J Environ Res Public Health. 2021 Feb 19. pii: 2053. [Epub ahead of print]18(4):
    Inorganic Fiber Lung Burden in Subjects with Occupational and/or Anthropogenic Environmental Asbestos Exposure in Broni (Pavia, Northern Italy): An SEM-EDS Study on Autoptic Samples.
    Silvia Damiana Visonà, Silvana Capella, Sofia Bodini, Paola Borrelli, Simona Villani, Eleonora Crespi, Andrea Frontini, Claudio Colosio, Elena Belluso.
      Increased mortality due to malignant mesothelioma has been demonstrated by several epidemiologic studies in the area around Broni (a small town in Lombardy, northern Italy), where a factory producing asbestos cement was active between 1932 and 1993. Until now, the inorganic fiber burden in lungs has not been investigated in this population. The aim of this study is to assess the lung fiber burden in 72 individuals with previous occupational and/or anthropogenic environmental exposure to asbestos during the activity of an important asbestos cement factory. Inorganic fiber lung burden was assessed in autoptic samples taken from individuals deceased from asbestos-related diseases using a scanning electron microscope equipped with an energy-dispersive spectrometer. Significant differences in the detected amount of asbestos were pointed out among the three types of exposure. In most lung samples taken from patients who died of mesothelioma, very little asbestos (or, in some cases, no fibers) was found. Such subjects showed a significantly lower median amount of asbestos as compared to asbestosis. Almost no chrysotile was detected in the examined samples. Overall, crocidolite was the most represented asbestos, followed by amosite, tremolite/actinolite asbestos, and anthophyllite asbestos. There were significant differences in the amount of crocidolite and amosite fibers according to the kind of exposure. Overall, these findings provide novel insights into the link between asbestos exposure and mesothelioma, as well as the different impacts of the various types of asbestos on human health in relation to their different biopersistences in the lung microenvironment.
    Keywords:  SEM-EDS; asbestos; asbestos bodies; lung fiber burden; malignant mesothelioma
    DOI:  https://doi.org/10.3390/ijerph18042053
  6. Toxicol In Vitro. 2021 Feb 27. pii: S0887-2333(21)00051-5. [Epub ahead of print] 105126
    Osteopontin mRNA expression by rat mesothelial cells exposed to multi-walled carbon nanotubes as a potential biomarker of chronic neoplastic transformation in vitro.
    Sreepradha Sridharan, Alexia Taylor-Just, James C Bonner.
      Mesothelioma is a cancer of the lung pleura primarily associated with inhalation of asbestos fibers. Multi-walled carbon nanotubes (MWCNTs) are engineered nanomaterials that pose a potential risk for mesothelioma due to properties that are similar to asbestos. Inhaled MWCNTs migrate to the pleura in rodents and some types cause mesothelioma. Like asbestos, there is a diversity of MWCNT types. We investigated the neoplastic potential of tangled (tMWCNT) versus rigid (rMWCNT) after chronic exposure using serial passages of rat mesothelial cells in vitro. Normal rat mesothelial (NRM2) cells were exposed to tMWCNTs or rMWCNTs for 45 weeks over 85 passages to determine if exposure resulted in transformation to a neoplastic phenotype. Rat mesothelioma (ME1) cells were used as a positive control. Osteopontin (OPN) mRNA was assayed as a biomarker of transformation by real time quantitative polymerase chain reaction (qPCR) and transformation was determined by a cell invasion assay. Exposure to rMWCNTs, but not tMWCNTs, resulted in transformation of NRM2 cells into an invasive phenotype that was similar to ME1 cells. Moreover, exposure of NRM2 cells to rMWCNTs increased OPN mRNA that correlated with cellular transformation. These data suggest that OPN is a potential biomarker that should be further investigated to screen the carcinogenicity of MWCNTs in vitro.
    Keywords:  Carbon nanotubes; Mesothelial cells; Mesothelioma; Osteopontin
    DOI:  https://doi.org/10.1016/j.tiv.2021.105126
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