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Zipprick J, Demir E, Krynska H, Köprülüoğlu S, Strauß K, Skribek M, Hutyra-gram Ötvös R, Gad AKB, Dobra K. Ex-Vivo Drug-Sensitivity Testing to Predict Clinical Response in Non-Small Cell Lung Cancer and Pleural Mesothelioma: A Systematic Review and Narrative Synthesis. Cancers (Basel) 2025; 17:986. [PMID: 40149320 PMCID: PMC11940109 DOI: 10.3390/cancers17060986] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2025] [Revised: 02/28/2025] [Accepted: 03/04/2025] [Indexed: 03/29/2025] Open
Abstract
Background/objectives: Non-small cell lung cancer and pleural mesothelioma are among the most lethal and therapy-resistant tumors in humans. These tumors are diagnosed late, frequently present pleural effusion and develop drug resistance, and the treatment is often inefficient and largely alliative. Therefore, there is an urgent need to refine the selection of drugs and patients for personalized treatment. Methods: To progress the field, we performed a systematic literature review in line with the PRISMA guidelines followed by a narrative synthesis approach to identify themes. Results: The literature to date shows, in general, a positive correlation between the drug-sensitivity of patient-derived cells ex vivo and the clinical outcome. However, only a handful of these studies show a numerical correlation. This, along with the vast diversity of correlated techniques and parameters makes it difficult to directly compare the findings. To build a common knowledge base for future studies, we therefore offer a comprehensive summary of the literature, identify gaps, and suggest future avenues for research. Conclusions: We present unified recommendations for the collection, preparation, and ex vivo sensitivity testing of samples for the future development of personalized medicine.
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Andreikos D, Spandidos DA, Georgakopoulou VE. Telomeres and telomerase in mesothelioma: Pathophysiology, biomarkers and emerging therapeutic strategies (Review). Int J Oncol 2025; 66:23. [PMID: 39981889 PMCID: PMC11844339 DOI: 10.3892/ijo.2025.5729] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2024] [Accepted: 02/10/2025] [Indexed: 02/22/2025] Open
Abstract
Malignant mesothelioma (MM) is a rare but aggressive cancer linked to asbestos exposure and characterized by advanced‑stage disease at presentation. Despite advances in treatment, prognosis remains abysmal, highlighting the imperative for the development of novel biomarkers and treatment approaches. Telomere biology plays a pivotal role in the tumorigenic process and has emerged as a key area in oncology research. Short telomeres have been associated with genomic instability, and substantially shorter telomere length (TL) has been identified in MM, showcasing the potential of TL in risk assessment, early detection, and disease progression monitoring. MM predominantly maintains TL through telomerase activity (TA), which in research has been identified in >90% of MM cases, underscoring the potential of TA as a biomarker in MM. Telomerase reverse transcriptase (TERT) polymorphisms may serve as valuable biomarkers, with research identifying associations between single nucleotide polymorphisms (SNPs) and the risk and prognosis of MM. Additionally, TERT promoter mutations have been associated with poor prognosis and advanced‑stage disease, with the non‑canonical functions of TERT hypothesized to contribute to the development of MM. TERT promoter mutations occur in ~12% of MM cases; C228T, C250T and A161C are the most common, while the distribution and frequency differ depending on histological subtype. Research reveals the promise of the various approaches therapeutically targeting telomerase, with favorable results in pre‑clinical models and inconclusive findings in clinical trials. The present review examines the role of telomere biology in MM and its implications in diagnosis, prognosis, and therapy.
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Affiliation(s)
- Dimitrios Andreikos
- School of Medicine, Democritus University of Thrace, 68110 Alexandroupolis, Greece
| | - Demetrios A. Spandidos
- Laboratory of Clinical Virology, School of Medicine, University of Crete, 71003 Heraklion, Greece
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Mayoral M, Araujo-Filho JAB, Tan KS, Ortiz E, Adusumilli PS, Rusch V, Zauderer M, Ginsberg MS. Are there features that can predict the unresectability of pleural mesothelioma? Eur Radiol 2025; 35:806-814. [PMID: 39143249 DOI: 10.1007/s00330-024-10963-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2024] [Revised: 05/22/2024] [Accepted: 06/27/2024] [Indexed: 08/16/2024]
Abstract
INTRODUCTION The current clinical staging of pleural mesothelioma (PM) is often discordant with the pathologic staging. This study aimed to identify clinical and radiological features that could help predict unresectability in PM. METHODS Twenty-two descriptive radiologic features were retrospectively evaluated on preoperative computed tomography (CT) and/or positron emission tomography/CT (PET/CT) performed in patients with presumably resectable PM who underwent surgery. Measurements of maximum and sum pleural thickness at three levels of the thorax (upper, middle, and lower) were taken and stratified based on the cutpoints provided by the International Association for the Study of Lung Cancer (IASLC). Clinical and radiological features, including clinical-stage, were compared between resectable and unresectable tumors by univariate analysis and logistic regression modeling. RESULTS Of 133 patients, 69/133 (52%) had resectable and 64/133 (48%) had unresectable PM. Asbestos exposure (p = 0.005), neoadjuvant treatment (p = 0.001), clinical T-stage (p < 0.0001), all pleural thickness measurements (p < 0.05), pleural thickness pattern (p < 0.0001) and degree (p = 0.033), lung invasion (p = 0.004), extrapleural space obliteration (p < 0.0001), extension to subphrenic space (p = 0.0004), and two combination variables representing extensive diaphragmatic contact and/or chest wall involvement (p = 0.002) and mediastinal invasion (p < 0.0001) were significant predictors at univariate analysis. At multivariable analysis, all models achieved a strong diagnostic performance (area under the curve (AUC) > 0.8). The two best-performing models were one that included the upper-level maximum pleural thickness, extrapleural space obliteration, and mediastinal infiltration (AUC = 0.876), and another that integrated clinical variables and radiological assessment through the clinical T-stage (AUC = 0.879). CONCLUSION Selected clinical and radiologic features, including pleural thickness measurements, appear to be strong predictors of unresectability in PM. CLINICAL RELEVANCE STATEMENT A more accurate prediction of unresectability in the preoperative assessment of patients with pleural mesothelioma may avoid unnecessary surgery and prompt initiation of nonsurgical treatments. KEY POINTS About half of pleural mesothelioma patients are reported to receive an incorrect disease stage preoperatively. Eleven features identified as predictors of unresectability were included in strongly performing predictive models. More accurate preoperative staging will help clinicians and patients choose the most appropriate treatments.
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Affiliation(s)
- Maria Mayoral
- Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA.
- Medical Imaging Department, Hospital Clinic of Barcelona, 170 Villarroel street, Barcelona, 08036, Spain.
| | | | - Kay See Tan
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA
| | - Eduardo Ortiz
- Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA
| | - Prasad S Adusumilli
- Department of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA
| | - Valerie Rusch
- Department of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA
| | - Marjorie Zauderer
- Department of Medical Oncology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA
| | - Michelle S Ginsberg
- Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA
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Elsayed HH, Sharkawy HY, Ahmed MA, Abdel-Gayed M, Eldewer M. Effect of intraoperative hyperthermic intrathoracic chemotherapy after pleurectomy decortication for treatment of malignant pleural mesothelioma: a comparative study. Updates Surg 2024; 76:2893-2901. [PMID: 39305357 PMCID: PMC11628442 DOI: 10.1007/s13304-024-01986-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2024] [Accepted: 08/30/2024] [Indexed: 12/10/2024]
Abstract
Malignant pleural mesothelioma (MPM) is an aggressive malignancy with few long-term survivors. Despite the dismal prognosis, hyperthermic intrathoracic chemoperfusion (HITOC) was shown to improve survival in a selective group of patients. We analyzed the influence of HITOC following pleurectomy and decortication on postoperative morbidity and overall survival for patients suffering from localized mesothelioma. From March 2017 until August 2023, 55 patients with localized pleural mesothelioma underwent pleurectomy and decortication. Thirty patients performed only surgery while 25 consecutive patients had surgery followed by HITOC with cisplatin (125 mg/m2) infused for 70 min at a temp of 40-43 °C. We analyzed postoperative morbidity, HITOC-related complications, and the influence of HITOC on survival. The trial was registered on 19/08/2022 as NCT05508555. The HITOC group had a mean age of 53.1 ± 8.2 years while the surgery group (non-HITOC) had a mean age of 52.1 ± 8.6 years. The HITOC group had 17 (68%) men, whereas the surgery group included 18 (60%) males. The 30-day mortality in the HITOC group was 0% vs 1 case (3.3%) in the surgery group. HITOC-related transient complications occurred in 4/25 (16%) of the HITOC group (atrial fibrillation, renal impairment and transient hypotension). Progression-free survival in the HITOC group was 8 months (95% CI 4.3-11.6) vs 6 months (95% CI 2.5-9.9) in the surgery-only group (p = 0.79). The overall survival time in the HITOC group was 28 months (95% CI 21.5-34.5) vs 22 months (95% CI 17.5-26.5) in the surgery-only group (p = 0.75). Risk factors analysis for recurrence in the HITOC group confirmed a significant role for early stages (p = 0.03). HITOC following pleurectomy and decortication is a safe therapeutic option that may improve survival for selected patients with localized epithelial pleural mesothelioma. Patients with earlier-stage mesothelioma are more likely to benefit from radical surgery and HITOC.
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Affiliation(s)
- Hany Hasan Elsayed
- Thoracic Surgery Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
| | - Hazem Youssef Sharkawy
- Cardiothoracic Surgery Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Mohammed Attia Ahmed
- Cardiothoracic Surgery Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Mohammed Abdel-Gayed
- Cardiothoracic Surgery Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Mostafa Eldewer
- Cardiothoracic Surgery Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt
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Zafar A, Rashid AA, Moeed A, Tahir MJ, Khan AJ, Shrateh ON, Ahmed A. Safety and efficacy of PD-1/PD-L1 immune checkpoint inhibitors in patients with pre-treated advanced stage malignant mesothelioma: a systematic review and meta-analysis. BMC Cancer 2024; 24:1353. [PMID: 39501196 PMCID: PMC11536716 DOI: 10.1186/s12885-024-13127-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2024] [Accepted: 10/29/2024] [Indexed: 11/09/2024] Open
Abstract
BACKGROUND Malignant mesothelioma is an aggressive cancer with poor prognosis. Programmed cell death protein-1 (PD-1) and its ligand 1 (PD-L1) immune checkpoint inhibitors (ICIs) have recently presented as a viable option in some first line but primarily as a second-line treatment of advanced-stage malignant mesothelioma (asMM). Therefore, this systematic review and meta-analysis aims to assess the safety and efficacy of PD-1/L-1 ICIs in advanced-stage malignant mesothelioma. METHODS PubMed, Scopus, and Cochrane databases were searched for all studies assessing the safety and efficacy of anti PD-1/PD-L1 agents. Primary outcomes were objective response rate (ORR) and disease control rate (DCR). Secondary outcomes were median progression free (mPFS) and overall survival (mOS). Safety outcomes were treatment- (TRAEs) and immune-related adverse events (IRAEs). A random-effects meta-analysis was performed to pool medians and to derive event rates. RESULTS A total of 15 studies were included with total of 1064 asMM patients. ORR and DCR were 16% and 57%, respectively. A pooled mPFS was 4.53 (CI: 3.40-5.65) and mOS was 10.51 (CI: 9.03-12.00). Overall TRAEs had an event rate of 0.69 (0.50-0.83) whereas IRAEs had an event rate of 0.28 (0.15-0.46). There were no significant differences between pembrolizumab, nivolumab primarily, and avelumab subgroups for all the outcomes. Additionally, meta-regression found no covariate to be a significant factor in ORR and DCR. CONCLUSION In this meta-analysis we found that anti-PD1/PD-L1 treatment could be useful in pretreated asMM as they had at least comparable or greater mPFS, mOS, ORR, and DCR than other second-line agents currently being used. REGISTRATION NUMBER This systematic review was registered at PROSPERO prior to the literature search, CRD42023442350.
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Affiliation(s)
| | - Asma Abdul Rashid
- Dow Medical College, Dow University of Health Sciences, Karachi, Pakistan
| | - Abdul Moeed
- Dow Medical College, Dow University of Health Sciences, Karachi, Pakistan
| | | | | | - Oadi N Shrateh
- Faculty of Medicine, Al-Quds University, Jerusalem, Palestine.
| | - Ali Ahmed
- Division of Infectious Diseases and Global Public Health, Department of Medicine, University of California, San Diego, CA, USA
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Andretta E, Costa A, Ventura E, Quintiliani M, Damiano S, Giordano A, Morrione A, Ciarcia R. Capsaicin Exerts Antitumor Activity in Mesothelioma Cells. Nutrients 2024; 16:3758. [PMID: 39519591 PMCID: PMC11547426 DOI: 10.3390/nu16213758] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2024] [Revised: 10/24/2024] [Accepted: 10/30/2024] [Indexed: 11/16/2024] Open
Abstract
BACKGROUND/OBJECTIVES Mesothelioma is an aggressive cancer with limited treatment options. Mesothelioma therapy often involves a multimodal approach including surgery, radiotherapy and chemotherapy. However, the prognosis for patients remains poor. Difficult diagnosis, late symptoms when the tumor is in an advanced stage and the onset of chemotherapy resistance make mesothelioma difficult to treat. For this reason, it is essential to discover new pharmacological approaches. Capsaicin (CAPS) is the active compound of chili peppers. Based on CAPS's anticancer properties on various tumor lines and its chemo-sensitizing action on resistant cells, in this study, we evaluated the effects of CAPS on mesothelioma cells to assess its potential use in mesothelioma therapy. METHODS To evaluate antiproliferative effects of CAPS, we performed MTS assays on various mesothelioma cells, representative of all major mesothelioma subtypes. Transwell migration and wound-healing assays were used to examine the effect of CAPS on mesothelioma cell migration. We also determined the effects of CAPS on oncogenic signaling pathways by assessing the levels of AKT and MAPK activation. RESULTS In this study, we show that CAPS significantly reduces proliferation of both parental and cisplatin-resistant mesothelioma cells. CAPS promotes S-phase cell cycle arrest and inhibits lateral motility and migration of mesothelioma cells. Accordingly, CAPS suppresses AKT and ERK1/2 activation in MSTO-211H and NCI-H2052 cells. Our results support an antitumor effect of CAPS on cisplatin-resistant mesothelioma cells, suggesting that it may reduce resistance to cisplatin. CONCLUSIONS Our results could pave the way for further studies to evaluate the use of CAPS for mesothelioma treatment.
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Affiliation(s)
- Emanuela Andretta
- Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, Department of Biology, College of Science and Technology, Temple University, Philadelphia, PA 19122, USA; (E.A.); (A.C.); (E.V.); (A.G.)
- Department of Veterinary Medicine and Animal Productions, University of Naples Federico II, 80137 Naples, Italy; (S.D.); (R.C.)
- Department of Chemical Sciences, University of Naples Federico II, via Cinthia, 4, 80126 Naples, Italy
| | - Aurora Costa
- Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, Department of Biology, College of Science and Technology, Temple University, Philadelphia, PA 19122, USA; (E.A.); (A.C.); (E.V.); (A.G.)
- Department of Medical Biotechnologies, University of Siena, 53100 Siena, Italy
| | - Elisa Ventura
- Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, Department of Biology, College of Science and Technology, Temple University, Philadelphia, PA 19122, USA; (E.A.); (A.C.); (E.V.); (A.G.)
| | | | - Sara Damiano
- Department of Veterinary Medicine and Animal Productions, University of Naples Federico II, 80137 Naples, Italy; (S.D.); (R.C.)
| | - Antonio Giordano
- Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, Department of Biology, College of Science and Technology, Temple University, Philadelphia, PA 19122, USA; (E.A.); (A.C.); (E.V.); (A.G.)
- Department of Medical Biotechnologies, University of Siena, 53100 Siena, Italy
| | - Andrea Morrione
- Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, Department of Biology, College of Science and Technology, Temple University, Philadelphia, PA 19122, USA; (E.A.); (A.C.); (E.V.); (A.G.)
| | - Roberto Ciarcia
- Department of Veterinary Medicine and Animal Productions, University of Naples Federico II, 80137 Naples, Italy; (S.D.); (R.C.)
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Rezvani A, Shahriarirad R, Jahanshahi S, Fouladi D, Tavallali M, Ziaian B, Fallahi MJ. The aftermath of asbestos prohibition in industry and its association with malignant mesothelioma in the south of Iran: An enduring predicament yet to be resolved. Health Sci Rep 2024; 7:e70117. [PMID: 39377019 PMCID: PMC11456676 DOI: 10.1002/hsr2.70117] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2024] [Revised: 08/16/2024] [Accepted: 09/18/2024] [Indexed: 10/09/2024] Open
Abstract
Purpose Malignant Mesothelioma (MM) is a rare malignancy of the serosa membranes with a high mortality rate and long latent period. The relationship between a group of mineral fibers known as asbestos and mesothelioma is now well accepted in which people can be exposed to these fibers by various means during their lifetime and has been its usage has banned in many countries, such as Iran, which announced its gradual elimination from 1999 over a period of 7 years by using safe substitutes. However, the mineral particles are able to sustain itself in the environment, air, water, and soil and on the other hand, symptoms may take up to half a century to develop in exposed individuals. Also, there remains a shortage of comprehensive investigation on the effects of asbestos exposure within the familial context (household or domestic exposure) or on individuals residing in proximity to asbestos mines or factories (environmental exposure). Based on the high number of MM cases in Iran, and also our hypothesis that residuals of asbestos in the environment and petroleum products may be the etiological factor for MM, we conducted this study to evaluate the clinic epidemiological features of MM in the south of Iran its relation to possible asbestos exposure. Methods In this study, we analyzed the demographic features and occupations of confirmed cases of MM in Shiraz, southern Iran along with the follow-up of the patients' disease from 2008 to 2018, while also comparing the features of our patients with a control group compromising of 105 non-MM patients. Results Among the 35 confirmed cases of MM, with an average age of 61 years, 9 (25.7%) were female, and 26 (74.3%) were male. During our assessment, 12 patients had already died, with a mean time of 11.26 months post-diagnosis. Our findings revealed a higher prevalence of MM among housekeepers and employees of oil companies. In comparison to the control group, individuals with occupational exposure and those residing near refinery locations were at a heightened risk of developing MM. However, based on regression analysis, only occupations associated with refineries exhibited a significant correlation with MM (p = 0.028; OR: 14.602; 95% CI: 1.328-160.499). Conclusion Both occupational and para-occupational exposure demonstrated a significant correlation with MM, whereas our regression analysis did not affirm geographical and environmental factors as contributors to MM. Despite the industry's prohibition of direct asbestos usage, the persistent existence of asbestos particles in the environment for decades, coupled with the long latency period of MM, warrants further investigation. Health authorities and policymakers should recognize this potential hazard, prompting an enhancement of early detection within at-risk groups.
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Affiliation(s)
- Alireza Rezvani
- Thoracic and Vascular Surgery Research CenterShiraz University of Medical ScienceShirazIran
- Bone Marrow Transplantation Center, Nemazi HospitalShiraz University of Medical SciencesShirazIran
| | - Reza Shahriarirad
- Thoracic and Vascular Surgery Research CenterShiraz University of Medical ScienceShirazIran
| | - Sahar Jahanshahi
- Student Research CommitteeShiraz University of Medical SciencesShirazIran
| | - Damoun Fouladi
- Thoracic and Vascular Surgery Research CenterShiraz University of Medical ScienceShirazIran
- Student Research CommitteeShiraz University of Medical SciencesShirazIran
| | - Maryam Tavallali
- College of Agricultural Engineering, Department of Water EngineeringShiraz UniversityShirazIran
| | - Bizhan Ziaian
- Thoracic and Vascular Surgery Research CenterShiraz University of Medical ScienceShirazIran
| | - Mohammad Javad Fallahi
- Thoracic and Vascular Surgery Research CenterShiraz University of Medical ScienceShirazIran
- Department of Internal Medicine, Nemazee HospitalShiraz University of Medical SciencesShirazIran
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Fanizzi A, Catino A, Bove S, Comes MC, Montrone M, Sicolo A, Signorile R, Perrotti P, Pizzutilo P, Galetta D, Massafra R. Transfer learning approach in pre-treatment CT images to predict therapeutic response in advanced malignant pleural mesothelioma. Front Oncol 2024; 14:1432188. [PMID: 39351354 PMCID: PMC11439621 DOI: 10.3389/fonc.2024.1432188] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2024] [Accepted: 08/15/2024] [Indexed: 10/04/2024] Open
Abstract
Introduction Malignant pleural mesothelioma (MPM) is a poor-prognosis disease. Owing to the recent availability of new therapeutic options, there is a need to better assess prognosis. The initial clinical response could represent a useful parameter. Methods We proposed a transfer learning approach to predict an initial treatment response starting from baseline CT scans of patients with advanced/unresectable MPM undergoing first-line systemic therapy. The therapeutic response has been assessed according to the mRECIST criteria by CT scan at baseline and after two to three treatment cycles. We used three slices of baseline CT scan as input to the pre-trained convolutional neural network as a radiomic feature extractor. We identified a feature subset through a double feature selection procedure to train a binary SVM classifier to discriminate responders (partial response) from non-responders (stable or disease progression). Results The performance of the prediction classifiers was evaluated with an 80:20 hold-out validation scheme. We have evaluated how the developed model was robust to variations in the slices selected by the radiologist. In our dataset, 25 patients showed an initial partial response, whereas 13 patients showed progressive or stable disease. On the independent test, the proposed model achieved a median AUC and accuracy of 86.67% and 87.50%, respectively. Conclusions The proposed model has shown high performance even by varying the reference slices. Novel tools could help to improve the prognostic assessment of patients with MPM and to better identify subgroups of patients with different therapeutic responsiveness.
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Affiliation(s)
- Annarita Fanizzi
- Laboratorio di Biostatistica e Bioinformatica, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Tumori 'Giovanni Paolo II', Bari, Italy
| | - Annamaria Catino
- Struttura Semplice Dipartimentale di Oncologia Medica Toracica, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Tumori 'Giovanni Paolo II', Bari, Italy
| | - Samantha Bove
- Laboratorio di Biostatistica e Bioinformatica, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Tumori 'Giovanni Paolo II', Bari, Italy
| | - Maria Colomba Comes
- Laboratorio di Biostatistica e Bioinformatica, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Tumori 'Giovanni Paolo II', Bari, Italy
| | - Michele Montrone
- Struttura Semplice Dipartimentale di Oncologia Medica Toracica, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Tumori 'Giovanni Paolo II', Bari, Italy
| | - Angela Sicolo
- Struttura Semplice Dipartimentale di Oncologia Medica Toracica, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Tumori 'Giovanni Paolo II', Bari, Italy
| | - Rahel Signorile
- Laboratorio di Biostatistica e Bioinformatica, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Tumori 'Giovanni Paolo II', Bari, Italy
| | - Pia Perrotti
- Struttura Semplice Dipartimentale di Oncologia Medica Toracica, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Tumori 'Giovanni Paolo II', Bari, Italy
| | - Pamela Pizzutilo
- Struttura Semplice Dipartimentale di Oncologia Medica Toracica, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Tumori 'Giovanni Paolo II', Bari, Italy
| | - Domenico Galetta
- Struttura Semplice Dipartimentale di Oncologia Medica Toracica, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Tumori 'Giovanni Paolo II', Bari, Italy
| | - Raffaella Massafra
- Laboratorio di Biostatistica e Bioinformatica, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Tumori 'Giovanni Paolo II', Bari, Italy
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Karatkevich D, Losmanova T, Zens P, Deng H, Dubey C, Zhang T, Casty C, Gao Y, Neppl C, Berezowska S, Wang W, Peng RW, Schmid RA, Dorn P, Marti TM. Chemotherapy increases CDA expression and sensitizes malignant pleural mesothelioma cells to capecitabine treatment. Sci Rep 2024; 14:18206. [PMID: 39107509 PMCID: PMC11303810 DOI: 10.1038/s41598-024-69347-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2024] [Accepted: 08/03/2024] [Indexed: 08/10/2024] Open
Abstract
The combination of cisplatin and pemetrexed remains the gold standard chemotherapy for malignant pleural mesothelioma (MPM), although resistance and poor response pose a significant challenge. Cytidine deaminase (CDA) is a key enzyme in the nucleotide salvage pathway and is involved in the adaptive stress response to chemotherapy. The cytidine analog capecitabine and its metabolite 5'-deoxy-5-fluorocytidine (5'-DFCR) are converted via CDA to 5-fluorouracil, which affects DNA and RNA metabolism. This study investigated a schedule-dependent treatment strategy, proposing that initial chemotherapy induces CDA expression, sensitizing cells to subsequent capecitabine treatment. Basal CDA protein expression was low in different mesothelioma cell lines but increased in the corresponding xenografts. Standard chemotherapy increased CDA protein levels in MPM cells in vitro and in vivo in a schedule-dependent manner. This was associated with epithelial-to-mesenchymal transition and with HIF-1alpha expression at the transcriptional level. In addition, pretreatment with cisplatin and pemetrexed in combination sensitized MPM xenografts to capecitabine. Analysis of a tissue microarray (TMA) consisting of samples from 98 human MPM patients revealed that most human MPM samples had negative CDA expression. While survival curves based on CDA expression in matched samples clearly separated, significance was not reached due to the limited sample size. In non-matched samples, CDA expression before but not after neoadjuvant therapy was significantly associated with worse overall survival. In conclusion, chemotherapy increases CDA expression in xenografts, which is consistent with our in vitro results in MPM and lung cancer. A subset of matched patient samples showed increased CDA expression after therapy, suggesting that a schedule-dependent treatment strategy based on chemotherapy and capecitabine may benefit a selected MPM patient population.
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Affiliation(s)
- Darya Karatkevich
- Department of General Thoracic Surgery, Inselspital, Bern University Hospital, University of Bern, Murtenstrasse 28, 3008, Bern, Switzerland
- Oncology-Thoracic Malignancies, Department for BioMedical Research, University of Bern, Bern, Switzerland
- Graduate School of Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland
| | - Tereza Losmanova
- Institute of Tissue Medicine and Pathology, University of Bern, Bern, Switzerland
| | - Philipp Zens
- Institute of Tissue Medicine and Pathology, University of Bern, Bern, Switzerland
| | - Haibin Deng
- Department of General Thoracic Surgery, Inselspital, Bern University Hospital, University of Bern, Murtenstrasse 28, 3008, Bern, Switzerland
- Oncology-Thoracic Malignancies, Department for BioMedical Research, University of Bern, Bern, Switzerland
- 2nd Department of Thoracic Surgery, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, Hunan, China
- Hunan Clinical Medical Research Center of Accurate Diagnosis and Treatment for Esophageal Carcinoma, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, Hunan, China
| | - Christelle Dubey
- Department of General Thoracic Surgery, Inselspital, Bern University Hospital, University of Bern, Murtenstrasse 28, 3008, Bern, Switzerland
- Oncology-Thoracic Malignancies, Department for BioMedical Research, University of Bern, Bern, Switzerland
| | - Tuo Zhang
- Department of General Thoracic Surgery, Inselspital, Bern University Hospital, University of Bern, Murtenstrasse 28, 3008, Bern, Switzerland
- Oncology-Thoracic Malignancies, Department for BioMedical Research, University of Bern, Bern, Switzerland
- Graduate School of Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland
| | - Corsin Casty
- Department of General Thoracic Surgery, Inselspital, Bern University Hospital, University of Bern, Murtenstrasse 28, 3008, Bern, Switzerland
- Oncology-Thoracic Malignancies, Department for BioMedical Research, University of Bern, Bern, Switzerland
| | - Yanyun Gao
- Department of General Thoracic Surgery, Inselspital, Bern University Hospital, University of Bern, Murtenstrasse 28, 3008, Bern, Switzerland
- Oncology-Thoracic Malignancies, Department for BioMedical Research, University of Bern, Bern, Switzerland
| | - Christina Neppl
- Institute of Tissue Medicine and Pathology, University of Bern, Bern, Switzerland
- Institute of Pathology, Heinrich-Heine University and University Hospital of Duesseldorf, Duesseldorf, Germany
| | - Sabina Berezowska
- Institute of Tissue Medicine and Pathology, University of Bern, Bern, Switzerland
- Department of Laboratory Medicine and Pathology, Institute of Pathology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
| | - Wenxiang Wang
- 2nd Department of Thoracic Surgery, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, Hunan, China
- Hunan Clinical Medical Research Center of Accurate Diagnosis and Treatment for Esophageal Carcinoma, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, Hunan, China
| | - Ren-Wang Peng
- Department of General Thoracic Surgery, Inselspital, Bern University Hospital, University of Bern, Murtenstrasse 28, 3008, Bern, Switzerland.
- Oncology-Thoracic Malignancies, Department for BioMedical Research, University of Bern, Bern, Switzerland.
| | - Ralph Alexander Schmid
- Department of General Thoracic Surgery, Inselspital, Bern University Hospital, University of Bern, Murtenstrasse 28, 3008, Bern, Switzerland.
- Oncology-Thoracic Malignancies, Department for BioMedical Research, University of Bern, Bern, Switzerland.
| | - Patrick Dorn
- Department of General Thoracic Surgery, Inselspital, Bern University Hospital, University of Bern, Murtenstrasse 28, 3008, Bern, Switzerland.
- Oncology-Thoracic Malignancies, Department for BioMedical Research, University of Bern, Bern, Switzerland.
| | - Thomas Michael Marti
- Department of General Thoracic Surgery, Inselspital, Bern University Hospital, University of Bern, Murtenstrasse 28, 3008, Bern, Switzerland.
- Oncology-Thoracic Malignancies, Department for BioMedical Research, University of Bern, Bern, Switzerland.
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10
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Chornkrathok S, Carbone M, Yang H, Rouf M, Dodson RF, Dera P. Mineralogical investigation of asbestos contamination of soil near old vermiculite processing plant in Honolulu, Hawai'i. ENVIRONMENTAL POLLUTION (BARKING, ESSEX : 1987) 2024; 356:124350. [PMID: 38857841 DOI: 10.1016/j.envpol.2024.124350] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/25/2024] [Revised: 06/06/2024] [Accepted: 06/07/2024] [Indexed: 06/12/2024]
Abstract
From 1954 to 1983, a vermiculite processing facility operated near the Honolulu airport and processed raw material from the Libby, Montana mine, which is now well known for the high asbestos content of its clay deposits. The factory was closed in 1983 due to health hazard concerns, and remediation was performed in 2001 as part of the Libby mine superfund project. However, because of close proximity of the closed-down facility to residential areas of metropolitan Honolulu, some concerns remain regarding the possible environmental persistence of the harmful contaminant. To assess the dispersion of asbestos-contaminated vermiculite and explore the impact of trade winds on its distribution, air samples, and soil samples were collected from multiple locations near the former vermiculite plant. Polarized light microscopy was employed to identify elongated minerals, including potential asbestos. Quantitative mineralogical analysis utilizing X-ray powder diffraction and Rietveld refinement revealed an average content of approximately 7% vermiculite and 4% tremolite at the site. The asbestiform nature of tremolite was confirmed through X-ray micro-diffraction. Detailed analysis of airborne samples using transmission electron microscopy revealed no detectable levels of asbestos fibers in the vicinity of the former processing facilities, but the possibility of asbestos fibers becoming airborne due to mechanical disturbance during dry weather cannot be ruled out.
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Affiliation(s)
- Sasithorn Chornkrathok
- Department of Earth Sciences, University of Hawai'i at Mānoa, Honolulu, HI, 96822, USA; Hawai'i Institute of Geophysics and Planetology, University of Hawai'i at Mānoa, Honolulu, HI, 96822, USA.
| | - Michele Carbone
- University of Hawai'i Cancer Center, University of Hawai'i at Mānoa, HI, 96813, USA
| | - Haining Yang
- University of Hawai'i Cancer Center, University of Hawai'i at Mānoa, HI, 96813, USA
| | - Mohammad Rouf
- Globeteck Group, Inc., 2800 Woodlawn Drive, Honolulu, HI, 96822, USA
| | | | - Przemyslaw Dera
- Hawai'i Institute of Geophysics and Planetology, University of Hawai'i at Mānoa, Honolulu, HI, 96822, USA
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11
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Liu RA, Wang BY, Chen X, Pu YQ, Zi JJ, Mei W, Zhang YP, Qiu L, Xiong W. Association Study of Pleural Mesothelioma and Oncogenic Simian Virus 40 in the Crocidolite-Contaminated Area of Dayao County, Yunnan Province, Southwest China. Genet Test Mol Biomarkers 2024; 28:189-198. [PMID: 38634609 DOI: 10.1089/gtmb.2023.0532] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/19/2024] Open
Abstract
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.
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Affiliation(s)
- Ru-Ai Liu
- Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Dali University, Dali, China
- Yunnan Provincial Key Laboratory of Clinical Biochemical Testing, Dali University, Dali, China
| | - Bo-Yong Wang
- Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Dali University, Dali, China
- Yunnan Provincial Key Laboratory of Clinical Biochemical Testing, Dali University, Dali, China
| | - Xin Chen
- Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Dali University, Dali, China
- Yunnan Provincial Key Laboratory of Clinical Biochemical Testing, Dali University, Dali, China
| | - Yuan-Qian Pu
- Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Dali University, Dali, China
- Yunnan Provincial Key Laboratory of Clinical Biochemical Testing, Dali University, Dali, China
| | - Jia-Ji Zi
- Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Dali University, Dali, China
- Yunnan Provincial Key Laboratory of Clinical Biochemical Testing, Dali University, Dali, China
- Yunnan Provincial Key Laboratory of Entomological Biopharmaceutical R&D, Dali University, Dali, China
| | - Wen Mei
- Department of Pathology, The First People's Hospital of Chuxiong Prefecture, Chuxiong, China
| | - Ye-Pin Zhang
- Department of Pathology, The First People's Hospital of Chuxiong Prefecture, Chuxiong, China
| | - Lu Qiu
- School of Chemistry and Life Sciences, Chuxiong Normal College, Chuxiong, China
| | - Wei Xiong
- Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Dali University, Dali, China
- Yunnan Provincial Key Laboratory of Clinical Biochemical Testing, Dali University, Dali, China
- Yunnan Provincial Key Laboratory of Entomological Biopharmaceutical R&D, Dali University, Dali, China
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12
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Marshall T, Lane J, Lahorra J. A Rare Presentation of Minimally Invasive Mesothelioma as a Large Tension Pneumothorax. Int J Surg Pathol 2024; 32:109-114. [PMID: 37128670 DOI: 10.1177/10668969231167492] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/03/2023]
Abstract
Development of mesothelioma is associated with asbestos exposure. Common presentations are with pleural-based plaques invading the chest wall and/or pleural effusion on chest imaging. The intent of this case report is to describe a rare presentation of mesothelioma, which presented atypically as a large tension pneumothorax. A 93-year-old male presented with a history of dyspnea that started after a coughing episode. On physical examination he was hemodynamically stable, but was hypoxic requiring 2L of supplemental oxygen. Computed tomography of the chest revealed a large right tension pneumothorax. A chest tube was placed and connected to suction (-20cmH20), but he continued to have an unresolving air leak over the following 2-week period. Upon video-assisted thoracotomy there were no blebs or adhesions seen. Right apical wedge resection and talc pleurodesis were performed. Pathologic examination revealed an atypical mesothelial cell proliferation with minimal, focal invasion into the pulmonary parenchyma. Tumor spread along the visceral pleura was thought to be the underlying cause of the pneumothorax. The surgical margins were uninvolved by the tumor, and the patient was later discharged home in stable condition. This was a rare presentation of what could best be described as minimally invasive mesothelioma arising in a background of probable mesothelioma in situ, which presented atypically as a large tension pneumothorax. This case highlighted the importance of establishing a pathologic diagnosis from pleural effusion cytology and/or pleural biopsy in persons presenting with spontaneous pneumothorax, and the difficulty in confirming a pathologic diagnosis of early mesothelial neoplasia.
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Affiliation(s)
- Tanya Marshall
- Department of Internal Medicine, Cleveland Clinic Akron General, Akron, OH, USA
- Pulmonary Critical Care Division, Allegheny General Hospital, Pittsburgh, PA, USA
| | - Jason Lane
- Department of Pathology, Cleveland Clinic Akron General, Akron, OH, USA
| | - Joseph Lahorra
- Department of Cardiothoracic Surgery, Cleveland Clinic Akron General, Akron, OH, USA
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13
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Lewis RC, Smith SJ, Krevanko CF, Hall ED, Miller EW, Beckett EM, Pierce JS. Occupational exposure to cosmetic talc and mesothelioma in barbers, hairdressers, and cosmetologists: A systematic review of the epidemiology. Toxicol Ind Health 2023; 39:564-582. [PMID: 37527434 DOI: 10.1177/07482337231191162] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/03/2023]
Abstract
Inhalation exposure to cosmetic talc has generated much scientific debate regarding its potential as a risk factor for mesothelioma, a rare, but fatal cancer. Barbers, hairdressers, and cosmetologists have regularly used cosmetic talc-containing products, but the collective epidemiological evidence for mesothelioma in these occupations has yet to be described. As such, we conducted a systematic review of PubMed and the National Institute for Occupational Safety and Health's (NIOSH) Numbered Publications list to identify original epidemiological literature reporting measures of association between these occupations and incidence of or death from mesothelioma. Literature screening was performed independently twice, the results of which were summarized and tabulated and underwent a review for their accuracy. A total of 12 studies met our inclusion criteria, including three cohort, six case-control, and three proportionate mortality/registration studies. The data from these studies were collected in 13 European and North American countries, spanning more than 50 years. We supplemented this review with queries of occupational mortality databases that are managed by the Washington State Department of Health and NIOSH for 26 U.S. states. Most findings were null and if statistically significant, nearly all showed an inverse relationship, indicative of a protective effect of these occupations on mesothelioma risk. Overall, the epidemiological evidence does not support an increased risk of mesothelioma for these occupations. This research fills an important data gap on the etiology of mesothelioma in barbers, hairdressers, and cosmetologists, and provides a benchmark for those with comparatively less exposure, such as non-occupational users of similar cosmetic talc-containing products.
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14
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Strange CD, Marom EM, Ahuja J, Shroff GS, Gladish GW, Carter BW, Truong MT. Imaging of Malignant Pleural, Pericardial, and Peritoneal Mesothelioma. Adv Anat Pathol 2023; 30:280-291. [PMID: 36395181 DOI: 10.1097/pap.0000000000000386] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
Malignant mesothelioma is a rare tumor arising from the mesothelial cells that line the pleura, pericardium, peritoneum, and tunica vaginalis. Imaging plays a primary role in the diagnosis, staging, and management of malignant mesothelioma. Multimodality imaging, including radiography, computed tomography (CT), magnetic resonance imaging (MRI), and F-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT), is used in a variety of scenarios, including diagnosis, guidance for tissue sampling, staging, and reassessment of disease after therapy. CT is the primary imaging modality used in staging. MRI has superior contrast resolution compared with CT and can add value in terms of determining surgical resectability in equivocal cases. MRI can further assess the degree of local invasion, particularly into the mediastinum, chest wall, and diaphragm, for malignant pleural and pericardial mesotheliomas. FDG PET/CT plays a role in the diagnosis and staging of malignant pleural mesothelioma (MPM) and has been shown to be more accurate than CT, MRI, and PET alone in the staging of malignant pleural mesothelioma. PET/CT can also be used to target lesions for biopsy and to assess prognosis, treatment response, and tumor recurrence.
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Affiliation(s)
- Chad D Strange
- Department of Thoracic Imaging, University of Texas MD Anderson Cancer Center, Houston, TX
| | - Edith M Marom
- Department of Diagnostic Radiology, Chaim Sheba Medical Center, Tel Aviv University, Ramat Gan, Israel
| | - Jitesh Ahuja
- Department of Thoracic Imaging, University of Texas MD Anderson Cancer Center, Houston, TX
| | - Girish S Shroff
- Department of Thoracic Imaging, University of Texas MD Anderson Cancer Center, Houston, TX
| | - Gregory W Gladish
- Department of Thoracic Imaging, University of Texas MD Anderson Cancer Center, Houston, TX
| | - Brett W Carter
- Department of Thoracic Imaging, University of Texas MD Anderson Cancer Center, Houston, TX
| | - Mylene T Truong
- Department of Thoracic Imaging, University of Texas MD Anderson Cancer Center, Houston, TX
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15
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SabzeAli N, Jaafarzadeh N, Shoushtari MH, Khadem M, Borsi SH, Zahedi A, Raji H. Investigation of asbestos concentration in ambient and lavage fluids of patients referred for bronchoscopy, Ahvaz. JOURNAL OF ENVIRONMENTAL HEALTH SCIENCE & ENGINEERING 2022; 20:641-646. [PMID: 36406611 PMCID: PMC9672228 DOI: 10.1007/s40201-022-00797-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/16/2020] [Revised: 02/19/2022] [Accepted: 03/13/2022] [Indexed: 06/16/2023]
Abstract
Introduction The amount of fibers in the lungs is considered to reflect the cumulative intensity of past asbestos exposure, and bronchoalveolar lavage (BAL) has been proposed to be a good indicator of the presence and quantity of asbestos particles in the lungs. This study evaluated the asbestos concentration in BAL fluids of asbestos-exposed and unexposed pulmonary patients and the environment of Ahvaz city. Methods This prospective study was conducted on 80 patients underwent diagnostic fiberoptic bronchoscopy referred to Imam Khomeini Hospital in Ahvaz, Iran, in 2019. Patients with Lung diseases were divided into three groups based on CT scan results: normal (n = 32), lung cancer (n = 40) and Interstitial lung disease (n = 8). The analysis of asbestos fiber concentration in BAL fluid was carried out by Scanning Electron Microscope (SEM). Results The positive asbestos test was detected in 69% of all subjects, including 64% of whom had asbestos-related jobs and 74.5% of those with non-related jobs (p = 0.240). The concentrations of asbestos fiber in the BAL in normal patients, lung cancer and interstitial fibrosis (ILD) were 8.13 ± 5.38, 9.66 ± 7.30 and 6.31 ± 1.98 f/ml, respectively (P = 0.492). There was no significant difference between the asbestos levels and exposure history (P = 0.877). The mean concentration of asbestos in the ambient air during the current year was 2.69 ± 0.57 f/ml (2.26-3.70), and the correlation between asbestos levels in BAL and the air was not significant (r = 0.147; P = 0.243). Conclusions The exposure of different occupational and non-occupational groups to this carcinogenic substance indicates the need for environmental and individual control measures to reduce and prevent asbestos exposure.
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Affiliation(s)
- Negar SabzeAli
- Air Pollution and Respiratory Diseases Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Nematollah Jaafarzadeh
- Environmental Technologies Research Center, Ahvaz Jundishapur university of medical sciences, Ahvaz, Iran
| | - Maryam Haddadzadeh Shoushtari
- Air Pollution and Respiratory Diseases Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Monireh Khadem
- Department of Occupational Health Engineering, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Seyed Hamid Borsi
- Air Pollution and Respiratory Diseases Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Amir Zahedi
- department of environmental health engineering, Ahvaz Jundishapur university of medical science, Ahvaz, Iran
| | - Hanieh Raji
- Air Pollution and Respiratory Diseases Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
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16
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Moro J, Sobrero S, Cartia CF, Ceraolo S, Rapanà R, Vaisitti F, Ganio S, Mellone F, Rudella S, Scopis F, La Paglia D, Cacciatore CC, Ruffini E, Leo F. Diagnostic and Therapeutic Challenges of Malignant Pleural Mesothelioma. Diagnostics (Basel) 2022; 12:3009. [PMID: 36553016 PMCID: PMC9776695 DOI: 10.3390/diagnostics12123009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2022] [Revised: 10/30/2022] [Accepted: 11/15/2022] [Indexed: 12/03/2022] Open
Abstract
Malignant pleural mesothelioma is a rare cancer characterized by a very poor prognosis. Exposure to asbestos is the leading cause of malignant pleural mesothelioma. The preinvasive lesions, the mesothelial hyperplasia and its possible evolution are the focus of the majority of the studies aiming to identify the treatable phase of the disease. The role of BAP-1 and MTAP in the diagnosis of mesothelioma in situ and in the prognosis of malignant pleural mesothelioma is the main topic of recent studies. The management of preinvasive lesions in mesothelioma is still unclear and many aspects are the subject of debate. The diagnosis, the disease staging and the accurate, comprehensive assessment of patients are three key instants for an appropriate management of patients/the disease.
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Affiliation(s)
- Jacopo Moro
- Thoracic Surgery Division, Department of Oncology, San Luigi Gonzaga Hospital Orbassano, University of Turin, 10043 Orbassano, Italy
| | - Simona Sobrero
- Thoracic Surgery Division, Department of Oncology, San Luigi Gonzaga Hospital Orbassano, University of Turin, 10043 Orbassano, Italy
| | | | - Simona Ceraolo
- Nursing Degree Program, Department of Clinical and Biological Sciences, University of Turin, 10124 Torino, Italy
| | - Roberta Rapanà
- Thoracic Surgery Division, Department of Oncology, San Luigi Gonzaga Hospital Orbassano, University of Turin, 10043 Orbassano, Italy
| | - Federico Vaisitti
- Thoracic Surgery Division, Department of Oncology, San Luigi Gonzaga Hospital Orbassano, University of Turin, 10043 Orbassano, Italy
| | - Stefano Ganio
- Thoracic Surgery Division, Department of Oncology, San Luigi Gonzaga Hospital Orbassano, University of Turin, 10043 Orbassano, Italy
| | - Federica Mellone
- Thoracic Surgery Division, Department of Oncology, San Luigi Gonzaga Hospital Orbassano, University of Turin, 10043 Orbassano, Italy
| | - Stefano Rudella
- Thoracic Surgery Division, Department of Oncology, San Luigi Gonzaga Hospital Orbassano, University of Turin, 10043 Orbassano, Italy
| | - Federico Scopis
- Thoracic Surgery Division, Department of Oncology, San Luigi Gonzaga Hospital Orbassano, University of Turin, 10043 Orbassano, Italy
| | - Danilo La Paglia
- Thoracic Surgery Division, Department of Oncology, San Luigi Gonzaga Hospital Orbassano, University of Turin, 10043 Orbassano, Italy
| | - Carola Crystel Cacciatore
- Thoracic Surgery Division, Department of Oncology, San Luigi Gonzaga Hospital Orbassano, University of Turin, 10043 Orbassano, Italy
| | - Enrico Ruffini
- Division of Thoracic Surgery, Department of Surgical Sciences, Città della Salute Hospital Turin, University of Turin, 10126 Torino, Italy
| | - Francesco Leo
- Thoracic Surgery Division, Department of Oncology, San Luigi Gonzaga Hospital Orbassano, University of Turin, 10043 Orbassano, Italy
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17
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Handra CM, Chirila M, Smarandescu RA, Ghita I. Near Missed Case of Occupational Pleural Malignant Mesothelioma, a Case Report and Latest Therapeutic Options. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:14763. [PMID: 36429481 PMCID: PMC9690238 DOI: 10.3390/ijerph192214763] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/06/2022] [Revised: 11/02/2022] [Accepted: 11/07/2022] [Indexed: 06/16/2023]
Abstract
Asbestos use started to be gradually banned in Europe from 1991 onwards, and there are currently strict occupational exposure limits for asbestos. However, malignant mesothelioma has a long latency time (in some cases up to 50-60 years), so the risks related to asbestos exposure should not be forgotten. Considering the increased risk of lung cancer following the inhalation of asbestos fibers, lifetime health monitoring should be considered in people occupationally exposed to asbestos, with an emphasis on the respiratory system. An assessment of their occupational history should be performed rigorously, especially in the areas with a history of asbestos production/use, as this is a key element for an early diagnosis and appropriate treatment. This case report presents a near-missed case of occupational pleural malignant mesothelioma. The latency time between the first asbestos exposure and the diagnosis of occupational pleural malignant mesothelioma was 49 years. The accurate diagnosis was made two years after the first symptoms appeared.
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Affiliation(s)
- Claudia-Mariana Handra
- Occupational Health Department, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania
| | - Marinela Chirila
- Faculty of Pharmacy, Titu Maiorescu University, 040441 Bucharest, Romania
| | - Raluca-Andreea Smarandescu
- Occupational Health Department, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania
| | - Isabel Ghita
- Pharmacy and Pharmacology Department, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania
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18
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Dusseault SK, Okobi OE, Thakral N, Sankar V, Gunawardene I, Dawkins B, Abu Y, Davis B. Primary Peritoneal Mesothelioma: Diagnostic Challenges of This Lethal Imposter. Case Rep Gastroenterol 2022; 16:588-594. [PMID: 36636360 PMCID: PMC9830302 DOI: 10.1159/000523935] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2021] [Accepted: 03/02/2022] [Indexed: 11/10/2022] Open
Abstract
Primary Peritoneal Mesothelioma is a rapidly aggressive and rare neoplasm that arises from the lining of mesothelial cells of the peritoneum and spreads extensively within the confines of the abdominal cavity. The pathogenesis of all forms of mesothelioma is strongly associated with industrial pollutants, of which asbestos is the principal carcinogen. Characteristically, asbestos exposure has a strong relationship with mesothelioma of the pleura, but the peritoneal cavity is the second most commonly affected site. Additionally, in contrast to pleural mesothelioma, which has a male predominance (male-female ratio of between four and five to one), women comprise approximately one-half of all cases of malignant peritoneal mesothelioma. A thorough history of occupational/paraoccupational exposure along with histopathology is the key to timely diagnosis and treatment.
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Affiliation(s)
- Sonya K. Dusseault
- Family Medicine, Lakeside Medical Center, Belle Glade, Florida, USA,*Sonya K. Dusseault, sonyadusseault6*gmail.com
| | | | - Nimish Thakral
- Internal medicine, Memorial Healthcare Systems, Pembroke Pines, Florida, USA
| | - Vignesh Sankar
- Nova Southeastern University College of Osteopathic Medicine, Davie, Florida, USA
| | | | - Bryan Dawkins
- Family Medicine, Lakeside Medical Center, Belle Glade, Florida, USA
| | - Yaw Abu
- Pulmonology/Critical Care, Lakeside Medical Center, Belle Glade, Florida, USA
| | - Barry Davis
- General Surgery, Lakeside Medical Center, Belle Glade, Florida, USA
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19
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ER Stress Response and Induction of Apoptosis in Malignant Pleural Mesothelioma: The Achilles Heel Targeted by the Anticancer Ruthenium Drug BOLD-100. Cancers (Basel) 2022; 14:cancers14174126. [PMID: 36077664 PMCID: PMC9454852 DOI: 10.3390/cancers14174126] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2022] [Revised: 08/02/2022] [Accepted: 08/23/2022] [Indexed: 11/17/2022] Open
Abstract
Simple Summary Malignant mesothelioma is a rare cancer arising from the serosal surfaces of the body, mainly from the pleural layer. This cancer, strongly linked to asbestos exposure, shows a very inauspicious prognosis. In fact, there is no efficient therapeutic treatment for malignant pleural mesothelioma (MPM). Thus, there is an urgent need to develop novel therapeutic approaches to treat this form of cancer. Our previous study showed the importance of GRP78 in MPM survival. BOLD-100 is a specific modulator of GRP78 and we have observed that it shows cytotoxicity against MPM cells. In particular, we describe that BOLD-100 increases oxidative stress and deregulates the calcium homeostasis leading to cell stress and, ultimately, to cell death. Our in vitro data strongly suggest that BOLD-100 inhibits the growth of MPM cell lines, proposing the application as a single agent, or in combination with other standard-of-care drugs, to treat MPM. Abstract Malignant mesothelioma is a rare cancer arising from the serosal surfaces of the body, mainly from the pleural layer. This cancer is strongly related to asbestos exposure and shows a very inauspicious prognosis, because there are scarce therapeutic options for this rare disease. Thus, there is an urgent need to develop novel therapeutic approaches to treat this form of cancer. To explore the biology of malignant pleural mesothelioma (MPM), we previously observed that MPM cell lines show high expression of the GRP78 protein, which is a chaperone protein and the master regulator of the unfolded protein response (UPR) that resides in the endoplasmic reticulum (ER). Based on our previous studies showing the importance of GRP78 in MPM, we observed that BOLD-100, a specific modulator of GRP78 and the UPR, shows cytotoxicity against MPM cells. Our studies demonstrated that BOLD-100 increases ROS production and Ca2+ release from the ER, leading to ER stress activation and, ultimately, to cell death. Our in vitro data strongly suggest that BOLD-100 inhibits the growth of MPM cell lines, proposing the application as a single agent, or in combination with other standard-of-care drugs, to treat MPM.
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Lopci E, Castello A, Mansi L. FDG PET/CT for Staging and Restaging Malignant Mesothelioma. Semin Nucl Med 2022; 52:806-815. [PMID: 35965111 DOI: 10.1053/j.semnuclmed.2022.07.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2022] [Revised: 07/19/2022] [Accepted: 07/25/2022] [Indexed: 11/11/2022]
Abstract
Malignant mesothelioma is an aggressive tumor originating from the mesothelial cells and presenting in general with a very poor prognosis. The pleural localization represents the prevailing disease site, while peritoneal involvement is commonly rare. The WHO classifies mesotheliomas into epithelioid, biphasic, and sarcomatoid histotypes, having diverse outcome with the sarcomatoid or biphasic forms showing the poorest prognosis. Given the peculiar rind-like pattern of growth, mesothelioma assessment is rather challenging for medical imagers. Conventional imaging is principally based on contrast-enhanced CT, while the role of functional and metabolic imaging is regarded as complementary. By focusing essentially on the staging and restaging role of [18F]FDG PET/CT in malignant mesotheliomas, the present review will summarize the available data present in literature and provide some hints on alternative imaging and future perspectives. Given the prevailing incidence of pleural disease, the majority of the information will be addressed on malignant pleural mesothelioma, although a summary of principal characteristics and imaging findings in patients with peritoneal mesothelioma will be also provided.
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Affiliation(s)
- Egesta Lopci
- Nuclear Medicine Unit, IRCCS - Humanitas Research Hospital, Milan, Italy.
| | - Angelo Castello
- Nuclear Medicine Unit, Fondazione IRCCS Ca' Granda, Milan, Italy
| | - Luigi Mansi
- Interuniversity Research Center for the Sustainable Development (CIRPS), Rome, Italy
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21
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Murphy F, Jacobsen NR, Di Ianni E, Johnston H, Braakhuis H, Peijnenburg W, Oomen A, Fernandes T, Stone V. Grouping MWCNTs based on their similar potential to cause pulmonary hazard after inhalation: a case-study. Part Fibre Toxicol 2022; 19:50. [PMID: 35854357 PMCID: PMC9297605 DOI: 10.1186/s12989-022-00487-6] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2022] [Accepted: 06/23/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND The EU-project GRACIOUS developed an Integrated Approach to Testing and Assessment (IATA) to support grouping high aspect ratio nanomaterials (HARNs) presenting a similar inhalation hazard. Application of grouping reduces the need to assess toxicity on a case-by-case basis and supports read-across of hazard data from substances that have the data required for risk assessment (source) to those that lack such data (target). The HARN IATA, based on the fibre paradigm for pathogenic fibres, facilitates structured data gathering to propose groups of similar HARN and to support read-across by prompting users to address relevant questions regarding HARN morphology, biopersistence and inflammatory potential. The IATA is structured in tiers, allowing grouping decisions to be made using simple in vitro or in silico methods in Tier1 progressing to in vivo approaches at the highest Tier3. Here we present a case-study testing the applicability of GRACIOUS IATA to form an evidence-based group of multiwalled carbon nanotubes (MWCNT) posing a similar predicted fibre-hazard, to support read-across and reduce the burden of toxicity testing. RESULTS The case-study uses data on 15 different MWCNT, obtained from the published literature. By following the IATA, a group of 2 MWCNT was identified (NRCWE006 and NM-401) based on a high degree of similarity. A pairwise similarity assessment was subsequently conducted between the grouped MWCNT to evaluate the potential to conduct read-across and fill data gaps required for regulatory hazard assessment. The similarity assessment, based on expert judgement of Tier 1 assay results, predicts both MWCNT are likely to cause a similar acute in vivo hazard. This result supports the possibility for read-across of sub-chronic and chronic hazard endpoint data for lung fibrosis and carcinogenicity between the 2 grouped MWCNT. The implications of accepting the similarity assessment based on expert judgement of the MWCNT group are considered to stimulate future discussion on the level of similarity between group members considered sufficient to allow regulatory acceptance of a read-across argument. CONCLUSION This proof-of-concept case-study demonstrates how a grouping hypothesis and IATA may be used to support a nuanced and evidence-based grouping of 'similar' MWCNT and the subsequent interpolation of data between group members to streamline the hazard assessment process.
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Affiliation(s)
- Fiona Murphy
- NanoSafety Group, Heriot-Watt University, Edinburgh, UK.
| | | | - Emilio Di Ianni
- National Research Centre for the Working Environment (NFA), Copenhagen, Denmark
| | | | - Hedwig Braakhuis
- National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands
| | - Willie Peijnenburg
- National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands
- Institute of Environmental Sciences, Leiden University, Leiden, The Netherlands
| | - Agnes Oomen
- National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands
| | | | - Vicki Stone
- NanoSafety Group, Heriot-Watt University, Edinburgh, UK
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22
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Alnefaie A, Albogami S, Asiri Y, Ahmad T, Alotaibi SS, Al-Sanea MM, Althobaiti H. Chimeric Antigen Receptor T-Cells: An Overview of Concepts, Applications, Limitations, and Proposed Solutions. Front Bioeng Biotechnol 2022; 10:797440. [PMID: 35814023 PMCID: PMC9256991 DOI: 10.3389/fbioe.2022.797440] [Citation(s) in RCA: 55] [Impact Index Per Article: 18.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2021] [Accepted: 05/18/2022] [Indexed: 11/13/2022] Open
Abstract
Adaptive immunity, orchestrated by B-cells and T-cells, plays a crucial role in protecting the body from pathogenic invaders and can be used as tools to enhance the body's defense mechanisms against cancer by genetically engineering these immune cells. Several strategies have been identified for cancer treatment and evaluated for their efficacy against other diseases such as autoimmune and infectious diseases. One of the most advanced technologies is chimeric antigen receptor (CAR) T-cell therapy, a pioneering therapy in the oncology field. Successful clinical trials have resulted in the approval of six CAR-T cell products by the Food and Drug Administration for the treatment of hematological malignancies. However, there have been various obstacles that limit the use of CAR T-cell therapy as the first line of defense mechanism against cancer. Various innovative CAR-T cell therapeutic designs have been evaluated in preclinical and clinical trial settings and have demonstrated much potential for development. Such trials testing the suitability of CARs against solid tumors and HIV are showing promising results. In addition, new solutions have been proposed to overcome the limitations of this therapy. This review provides an overview of the current knowledge regarding this novel technology, including CAR T-cell structure, different applications, limitations, and proposed solutions.
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Affiliation(s)
- Alaa Alnefaie
- Department of Medical Services, King Faisal Medical Complex, Taif, Saudi Arabia
| | - Sarah Albogami
- Department of Biotechnology, College of Science, Taif University, Taif, Saudi Arabia
| | - Yousif Asiri
- Department of Clinical Pharmacy, College of Pharmacy, Taif University, Taif, Saudi Arabia
| | - Tanveer Ahmad
- Multidisciplinary Centre for Advanced Research and Studies, Jamia Millia Islamia, New Delhi, India
| | - Saqer S. Alotaibi
- Department of Biotechnology, College of Science, Taif University, Taif, Saudi Arabia
| | - Mohammad M. Al-Sanea
- Department of Pharmaceutical Chemistry, College of Pharmacy, Jouf University, Sakaka, Saudi Arabia
| | - Hisham Althobaiti
- Chief of Medical Department, King Faisal Medical Complex (KFMC), Taif, Saudi Arabia
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Banna GL, Signori A, Curioni-Fontecedro A, Cortellini A, Ponzano M, Giunta EF, Rebuzzi SE, Chan S, Gebbia V, van Eeden R, Addeo A, Ottensmeier C. Systemic therapy for pre-treated malignant mesothelioma: A systematic review, meta-analysis and network meta-analysis of randomised controlled trials. Eur J Cancer 2022; 166:287-299. [PMID: 35358809 DOI: 10.1016/j.ejca.2022.02.030] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2022] [Accepted: 02/27/2022] [Indexed: 12/25/2022]
Abstract
BACKGROUND Randomised controlled trials (RCTs) with systemic therapies for patients with pre-treated mesothelioma have reported equivocal efficacy results and generated a degree of clinical uncertainty about the choice of active treatment in this poor prognosis malignancy. METHODS To compare the effectiveness and safety and weigh the benefit of different systemic treatments in patients with pre-treated mesothelioma by systematic review, meta-analysis and network meta-analysis of RCTs. Full-text articles and abstracts were searched on PubMed, EMBASE, Cochrane Library and oncology conferences proceedings from 2005 through November 2021 for phase 2 and 3 RCTs. The protocol was submitted to the PROSPERO registry. Reporting followed the PRISMA guideline. Outcomes of interest were overall survival (OS) and progression-free (PFS), grade ≥3 treatment-related (Tr) adverse events (AEs), Tr-deaths and Tr-AEs leading to treatment discontinuation. FINDINGS Nine trials at low risk of bias by Cochrane Collaboration's methodology were included, encompassing 2789 patients. Five studies showed PFS benefit in the experimental treatment. In two studies, OS was prolonged by immunotherapy (versus placebo) or by adding an antiangiogenic agent to chemotherapy. Reported Tr-AE were lower with single-agent anti-PD1 compared with chemotherapy or placebo. The meta-analysis revealed a beneficial global effect on OS and PFS from experimental treatments (HR 0.86, 95% CI 0.77-0.96, p = 0.0083 and HR 0.79, 95% CI 0.72-0.86, p < 0.001), that for the PFS significantly favoured the comparison with non-active treatments (HR 0.73, 95% CI 0.66-0.81, p < 0.001). Younger patients (i.e. <65-70 years) appeared to benefit the most in OS (HR 0.71, 95% CI 0.55-0.92, p = 0.04). The risk of serious Tr-AEs and Tr-deaths was not significantly increased by experimental treatments (RR 1.38, 95% CI 0.81-2.35, p = 0.24 and RR 2.07, 95% CI 0.69-6.24, p = 0.19, respectively) that instead increased TrAEs leading to treatment discontinuation (RR 2.9, 95% CI 1.44-6.08, p = 0.003). The network meta-analysis did not identify any superior treatment in PFS. INTERPRETATION For patients with pre-treated MPM, single-agent anti-PD1 or chemotherapy ± the antiangiogenic agent can be considered active and safe systemic therapeutic options, particularly for younger patients.
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Affiliation(s)
| | - Alessio Signori
- Department of Health Sciences Section of Biostatistics, University of Genova, Genoa, Italy
| | | | - Alessio Cortellini
- Department of Surgery and Cancer, Imperial College London, Faculty of Medicine, Hammersmith Hospital, London, United Kingdom
| | - Marta Ponzano
- Department of Health Sciences Section of Biostatistics, University of Genova, Genoa, Italy
| | - Emilio Francesco Giunta
- Department of Experimental Medicine, Università Degli Studi Della Campania Luigi Vanvitelli, Naples, Italy
| | | | - Samuel Chan
- Oncology Department, Portsmouth Hospitals University NHS Trust, Portsmouth, United Kingdom
| | | | - Ronwyn van Eeden
- The Medical Oncology Centre of Rosebank, University of the Witwatersrand, Johannesburg, South Africa
| | - Alfredo Addeo
- Department of Oncology, Geneva University Hospital, Geneve, Switzerland
| | - Christian Ottensmeier
- Department of Molecular & Clinical Cancer Medicine, University of Liverpool, Liverpool, UK
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Saleh DM, Luo S, Ahmed OHM, Alexander DB, Alexander WT, Gunasekaran S, El-Gazzar AM, Abdelgied M, Numano T, Takase H, Ohnishi M, Tomono S, Hady RHAE, Fukamachi K, Kanno J, Hirose A, Xu J, Suzuki S, Naiki-Ito A, Takahashi S, Tsuda H. Assessment of the toxicity and carcinogenicity of double-walled carbon nanotubes in the rat lung after intratracheal instillation: a two-year study. Part Fibre Toxicol 2022; 19:30. [PMID: 35449069 PMCID: PMC9026941 DOI: 10.1186/s12989-022-00469-8] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2021] [Accepted: 04/07/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Considering the expanding industrial applications of carbon nanotubes (CNTs), safety assessment of these materials is far less than needed. Very few long-term in vivo studies have been carried out. This is the first 2-year in vivo study to assess the effects of double walled carbon nanotubes (DWCNTs) in the lung and pleura of rats after pulmonary exposure. METHODS Rats were divided into six groups: untreated, Vehicle, 3 DWCNT groups (0.12 mg/rat, 0.25 mg/rat and 0.5 mg/rat), and MWCNT-7 (0.5 mg/rat). The test materials were administrated by intratracheal-intrapulmonary spraying (TIPS) every other day for 15 days. Rats were observed without further treatment until sacrifice. RESULTS DWCNT were biopersistent in the rat lung and induced marked pulmonary inflammation with a significant increase in macrophage count and levels of the chemotactic cytokines CCL2 and CCL3. In addition, the 0.5 mg DWCNT treated rats had significantly higher pulmonary collagen deposition compared to the vehicle controls. The development of carcinomas in the lungs of rats treated with 0.5 mg DWCNT (4/24) was not quite statistically higher (p = 0.0502) than the vehicle control group (0/25), however, the overall incidence of lung tumor development, bronchiolo-alveolar adenoma and bronchiolo-alveolar carcinoma combined, in the lungs of rats treated with 0.5 mg DWCNT (7/24) was statistically higher (p < 0.05) than the vehicle control group (1/25). Notably, two of the rats treated with DWCNT, one in the 0.25 mg group and one in the 0.5 mg group, developed pleural mesotheliomas. However, both of these lesions developed in the visceral pleura, and unlike the rats administered MWCNT-7, rats administered DWCNT did not have elevated levels of HMGB1 in their pleural lavage fluids. This indicates that the mechanism by which the mesotheliomas that developed in the DWCNT treated rats is not relevant to humans. CONCLUSIONS Our results demonstrate that the DWCNT fibers we tested are biopersistent in the rat lung and induce chronic inflammation. Rats treated with 0.5 mg DWCNT developed pleural fibrosis and lung tumors. These findings demonstrate that the possibility that at least some types of DWCNTs are fibrogenic and tumorigenic cannot be ignored.
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Affiliation(s)
- Dina Mourad Saleh
- Nanotoxicology Lab Project, Nagoya City University, 3-1 Tanabe-Dohri, Mizuho-ku, Nagoya, 467-8603, Japan
- Department of Experimental Pathology and Tumor Biology, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Japan
- Department of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Assuit University, Assuit, Egypt
| | - Shengyong Luo
- College of Basic Medical Sciences, Anhui Medical University, Hefei, China
| | - Omnia Hosny Mohamed Ahmed
- Nanotoxicology Lab Project, Nagoya City University, 3-1 Tanabe-Dohri, Mizuho-ku, Nagoya, 467-8603, Japan
- Department of Experimental Pathology and Tumor Biology, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Japan
- Department of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Aswan University, Aswan, Egypt
| | - David B Alexander
- Nanotoxicology Lab Project, Nagoya City University, 3-1 Tanabe-Dohri, Mizuho-ku, Nagoya, 467-8603, Japan.
| | - William T Alexander
- Nanotoxicology Lab Project, Nagoya City University, 3-1 Tanabe-Dohri, Mizuho-ku, Nagoya, 467-8603, Japan
| | - Sivagami Gunasekaran
- Nanotoxicology Lab Project, Nagoya City University, 3-1 Tanabe-Dohri, Mizuho-ku, Nagoya, 467-8603, Japan
- Department of Experimental Pathology and Tumor Biology, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Japan
| | - Ahmed M El-Gazzar
- Department of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, Alexandria University, Alexandria, Egypt
| | - Mohamed Abdelgied
- Department of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, Beni-Suef University, Beni-Suef, Egypt
- Department of Pediatrics and Human Development, Michigan State University, Michigan, USA
| | - Takamasa Numano
- Nanotoxicology Lab Project, Nagoya City University, 3-1 Tanabe-Dohri, Mizuho-ku, Nagoya, 467-8603, Japan
| | - Hiroshi Takase
- Core Laboratory, Graduate School of Medicine, Nagoya City University, Nagoya, Japan
| | - Makoto Ohnishi
- Japan Industrial Safety and Health Association, Japan Bioassay Research Center, Hadano, Kanagawa, Japan
| | - Susumu Tomono
- Department of Microbiology and Immunology, Aichi Medical University School of Medicine, Nagakute, Japan
| | - Randa Hussein Abd El Hady
- Department of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Assuit University, Assuit, Egypt
| | - Katsumi Fukamachi
- Department of Neurotoxicology, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Japan
| | - Jun Kanno
- National Institute Hygienic Sciences, Kawasaki, Japan
| | | | - Jiegou Xu
- Nanotoxicology Lab Project, Nagoya City University, 3-1 Tanabe-Dohri, Mizuho-ku, Nagoya, 467-8603, Japan
- Department of Immunology, School of Basic Medical Sciences, Anhui Medical University, Hefei, China
| | - Shugo Suzuki
- Department of Molecular Pathology, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
| | - Aya Naiki-Ito
- Department of Experimental Pathology and Tumor Biology, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Japan
| | - Satoru Takahashi
- Department of Experimental Pathology and Tumor Biology, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Japan
| | - Hiroyuki Tsuda
- Nanotoxicology Lab Project, Nagoya City University, 3-1 Tanabe-Dohri, Mizuho-ku, Nagoya, 467-8603, Japan.
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Volpi F, D’Amore CA, Colligiani L, Milazzo A, Cavaliere S, De Liperi A, Neri E, Romei C. The Use of Chest Magnetic Resonance Imaging in Malignant Pleural Mesothelioma Diagnosis. Diagnostics (Basel) 2022; 12:diagnostics12030750. [PMID: 35328305 PMCID: PMC8946868 DOI: 10.3390/diagnostics12030750] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2022] [Revised: 03/15/2022] [Accepted: 03/16/2022] [Indexed: 12/10/2022] Open
Abstract
In recent years, many articles have demonstrated that magnetic resonance imaging (MRI) may be performed successfully in the study of the chest. The aim of this study was to evaluate the potential role of MRI in the differentiation of benign from malignant pleural disease with a special focus on malignant pleural mesothelioma and on MRI protocols. A systematic literature search was performed to find original articles about chest MRI in patients with either benign or malignant pleural disease. We retrieved 1246 papers and 17 studies were finally identified as being in accordance with our purpose. For a morphologic assessment, T1-weighted and T2-weighted sequences were usually performed, eventually associated with T1 post-contrast sequences for better detection of pleural lesions. Functional sequences such as Diffusion Weighting Imaging (DWI), associated with the evaluation of Apparent Diffusion Coefficient (ADC) maps, were lately and gradually introduced in chest MRI protocols and their potentiality in differentiating benign from malignant disease has been investigated by many authors. Many progresses have been performed to improve quality images and diagnostic performances of MRI. A better and early identification of pleural disease may be obtained, providing MRI as a possible tool that can differentiate malignant from benign pleural disease without using invasive procedures.
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Affiliation(s)
- Federica Volpi
- Department of Translational Research, Academic Radiology, University of Pisa, 56126 Pisa, Italy; (F.V.); (C.A.D.); (L.C.); (A.M.); (E.N.)
| | - Caterina A. D’Amore
- Department of Translational Research, Academic Radiology, University of Pisa, 56126 Pisa, Italy; (F.V.); (C.A.D.); (L.C.); (A.M.); (E.N.)
| | - Leonardo Colligiani
- Department of Translational Research, Academic Radiology, University of Pisa, 56126 Pisa, Italy; (F.V.); (C.A.D.); (L.C.); (A.M.); (E.N.)
| | - Alessio Milazzo
- Department of Translational Research, Academic Radiology, University of Pisa, 56126 Pisa, Italy; (F.V.); (C.A.D.); (L.C.); (A.M.); (E.N.)
| | - Silvia Cavaliere
- Department of Diagnostic Imaging, Diagnostic Radiology 2, Pisa University Hospital, 56124 Pisa, Italy; (S.C.); (A.D.L.)
| | - Annalisa De Liperi
- Department of Diagnostic Imaging, Diagnostic Radiology 2, Pisa University Hospital, 56124 Pisa, Italy; (S.C.); (A.D.L.)
| | - Emanuele Neri
- Department of Translational Research, Academic Radiology, University of Pisa, 56126 Pisa, Italy; (F.V.); (C.A.D.); (L.C.); (A.M.); (E.N.)
| | - Chiara Romei
- Department of Diagnostic Imaging, Diagnostic Radiology 2, Pisa University Hospital, 56124 Pisa, Italy; (S.C.); (A.D.L.)
- Correspondence:
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Cantini L, Laniado I, Murthy V, Sterman D, Aerts JGJV. Immunotherapy for mesothelioma: Moving beyond single immune check point inhibition. Lung Cancer 2022; 165:91-101. [PMID: 35114509 DOI: 10.1016/j.lungcan.2022.01.016] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2022] [Accepted: 01/20/2022] [Indexed: 12/29/2022]
Abstract
Malignant pleural mesothelioma (MPM) is an aggressive neoplasm with low survival rates. Platinum-based chemotherapy has represented the cornerstone of treatment for over a decade, prompting the investigation of new therapeutic strategies both in the early stage of the disease and in the advanced setting. The advent of immune check-point inhibitors (ICIs) has recently revamped the enthusiasm for using immunotherapy also in MPM. However, results from first clinical trials using single immune check-point inhibition have been conflicting, and this may be mainly attributed to the lack of specific biomarkers as well as to intra- and inter- patient heterogeneity. The phase III Checkmate743 firstly demonstrated the superiority of an ICI combination (nivolumab plus ipilimumab) over chemotherapy in the first-line treatment of unresectable MPM, leading to FDA approval of this regimen and showing that moving beyond single immune check point inhibition might be a successful strategy to overcome resistance in the majority of MPM patients. In this review, we describe the emerging immunotherapy strategies for the treatment of MPM. We also discuss how refining the approach in pre-clinical studies towards a more holistic perspective (which takes into account not only genetic but also pathophysiological vulnerabilities) and strengthening multi-institutional collaboration in clinical trials is finally helping the clinical development of immunotherapy in MPM.
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Affiliation(s)
- Luca Cantini
- Department of Pulmonary Medicine, Erasmus MC Cancer Institute, Rotterdam, the Netherlands; Clinical Oncology, Università Politecnica Delle Marche, AOU Ospedali Riuniti Ancona, Italy
| | - Isaac Laniado
- Division of Pulmonary, Critical Care, and Sleep Medicine, New York University (NYU), School of Medicine/NYU Langone Medical Center, New York, NY, United States
| | - Vivek Murthy
- Division of Pulmonary, Critical Care, and Sleep Medicine, New York University (NYU), School of Medicine/NYU Langone Medical Center, New York, NY, United States
| | - Daniel Sterman
- Division of Pulmonary, Critical Care, and Sleep Medicine, New York University (NYU), School of Medicine/NYU Langone Medical Center, New York, NY, United States
| | - Joachim G J V Aerts
- Department of Pulmonary Medicine, Erasmus MC Cancer Institute, Rotterdam, the Netherlands.
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Anobile DP, Montenovo G, Pecoraro C, Franczak M, Ait Iddouch W, Peters GJ, Riganti C, Giovannetti E. Splicing deregulation, microRNA and notch aberrations: fighting the three-headed dog to overcome drug resistance in malignant mesothelioma. Expert Rev Clin Pharmacol 2022; 15:305-322. [PMID: 35533249 DOI: 10.1080/17512433.2022.2074835] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2021] [Accepted: 05/04/2022] [Indexed: 12/20/2022]
Abstract
INTRODUCTION Malignant mesothelioma (MMe) is an aggressive rare cancer of the mesothelium, associated with asbestos exposure. MMe is currently an incurable disease at all stages mainly due to resistance to treatments. It is therefore necessary to elucidate key mechanisms underlying chemoresistance, in an effort to exploit them as novel therapeutic targets. AREAS COVERED Chemoresistance is frequently elicited by microRNA (miRNA) alterations and splicing deregulations. Indeed, several miRNAs, such as miR-29c, have been shown to exert oncogenic or oncosuppressive activity. Alterations in the splicing machinery might also be involved in chemoresistance. Moreover, the Notch signaling pathway, often deregulated in MMe, plays a key role in cancer stem cells formation and self-renewal, leading to drug resistance and relapses. EXPERT OPINION The prognosis of MMe in patients varies among different tumors and patient characteristics, and novel biomarkers and therapies are warranted. This work aims at giving an overview of MMe, with a special focus on state-of-the-art treatments and new therapeutic strategies against vulnerabilities emerging from studies on epigenetics factors. Besides, this review is also the first to discuss the interplay between miRNAs and alternative splicing as well as the role of Notch as new promising frontiers to overcome drug resistance in MMe.
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Affiliation(s)
- Dario P Anobile
- Department of Medical Oncology, VU University Medical Center, Cancer Center Amsterdam, Amsterdam, Netherlands
- Department of Oncology, University of Torino, Orbassano, Italy
| | - Giulia Montenovo
- Department of Medical Oncology, VU University Medical Center, Cancer Center Amsterdam, Amsterdam, Netherlands
- Department of Medicine and Surgery, University of Parma, Parma, Italy
| | - Camilla Pecoraro
- Department of Medical Oncology, VU University Medical Center, Cancer Center Amsterdam, Amsterdam, Netherlands
- Farmaceutiche (STEBICEF), Università degli Studi di PalermoDipartimento Di Scienze E Tecnologie Biologiche Chimiche E , Palermo, Italy
| | - Marika Franczak
- Department of Medical Oncology, VU University Medical Center, Cancer Center Amsterdam, Amsterdam, Netherlands
- Department of Biochemistry, Medical University of Gdansk, 80-210 Gdansk, Poland
| | - Widad Ait Iddouch
- Department of Medical Oncology, VU University Medical Center, Cancer Center Amsterdam, Amsterdam, Netherlands
| | - Godefridus J Peters
- Department of Medical Oncology, VU University Medical Center, Cancer Center Amsterdam, Amsterdam, Netherlands
- Department of Biochemistry, Medical University of Gdansk, 80-210 Gdansk, Poland
| | - Chiara Riganti
- Department of Oncology, University of Torino, Orbassano, Italy
| | - Elisa Giovannetti
- Department of Medical Oncology, VU University Medical Center, Cancer Center Amsterdam, Amsterdam, Netherlands
- Fondazione Pisana per la Scienza Pisa, 56100 Pisa, Italy
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Visci G, Rizzello E, Zunarelli C, Violante FS, Boffetta P. Relationship between exposure to ionizing radiation and mesothelioma risk: A systematic review of the scientific literature and meta-analysis. Cancer Med 2022; 11:778-789. [PMID: 35029060 PMCID: PMC8817084 DOI: 10.1002/cam4.4436] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2021] [Revised: 11/05/2021] [Accepted: 11/06/2021] [Indexed: 11/23/2022] Open
Abstract
BACKGROUND Ionizing radiation and mesothelioma have been examined among personnel employed in nuclear power plant and patients treated by external beam radiation therapy (EBRT). The association is still controversial; the purpose of this review is to summarize the scientific evidence published in the literature regarding the relationship between ionizing radiation and incidence of mesothelioma and, if possible, estimating strongness of the association by meta-analysis of extracted data. METHODS Articles included in the systematic review were retrieved by searching among the three main scientific databases: PubMed, Scopus, and Embase. The literature search was conducted in June 2021. A meta-analysis of random effects was conducted, stratified by exposure (EBRT, occupational exposure). The heterogeneity of the summary relative risks (RRs) was assessed using I2 statistics. Publication bias was evaluated graphically through the funnel plot. FINDINGS The exposure to ionizing radiation could be a risk factor for mesothelioma: both for exposure to high doses for short periods (EBRT) (RR of 3.34 [95% confidence interval, CI 1.24-8.99]) and for exposure to low doses for a prolonged duration (exposure working) (RR of 3.57 [95% CI 2.16-5.89]). CONCLUSIONS Despite the low number of mesotheliomas in the general population, the steadily increased risk among individuals exposed to radiation is still worth considering.
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Affiliation(s)
- Giovanni Visci
- IRCCS Azienda Ospedaliero‐Universitaria di BolognaBolognaItaly
| | | | | | - Francesco Saverio Violante
- IRCCS Azienda Ospedaliero‐Universitaria di BolognaBolognaItaly
- Department of Medical and Surgical SciencesUniversity of BolognaBolognaItaly
| | - Paolo Boffetta
- Department of Medical and Surgical SciencesUniversity of BolognaBolognaItaly
- Stony Brook Cancer CenterStony Brook UniversityStony BrookNew YorkUSA
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29
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[Analysis of the Efficacy of Pemetrexed Maintenance Therapy in Patients with
Malignant Pleural Mesothelioma]. ZHONGGUO FEI AI ZA ZHI = CHINESE JOURNAL OF LUNG CANCER 2022; 25:7-13. [PMID: 35078279 PMCID: PMC8796129 DOI: 10.3779/j.issn.1009-3419.2021.101.48] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
BACKGROUND Malignant pleural mesothelioma (MPM) is a highly aggressive disease arising from pleural mesothelial cells. Advanced pleural mesothelioma has a poor prognosis, with a median survival of no more than 15 months. First line standard chemotherapy regimen recommended is Pemetrexed based chemotherapy regimen, with or without bevacizumab. There is no consensus on whether patients who have received first-line standard chemotherapy can benefit from pemetrexed maintenance chemotherapy. The study aimed to investigate the efficacy and safety of pemetrexed maintenance therapy (PMT) after treatment with a pemetrexed and platinum regimen for patients with MPM. METHODS A total of 40 MPM patients were collected from Cancer Hospital Chinese Academy of Medical Sciences from January 2013 to January 2018, eligible patients were unresectable MPM, without disease progression following 4 to 6 cycles of pemetrexed and platinum, including pemetrexed maintenance therapy group (22 cases) and observation group (18 cases). The last follow-up was conducted in January 2020. The primary endpoint were progression free survival (PFS), and the secondary end points were overall survival (OS), the efficacy, adverse reactions of PMT. RESULTS The median PFS in the PMT arm was longer than that in the observation arm (8.5 mon vs 3 mon, P=0.008), but there was no significant difference in median OS (26.4 mon vs 15.7 mon, P=0.177). Objective response rate (ORR) of two group were 22.7% and 0%, respectively. The grade 3-4 toxicity in PMT group included grade 4 neutropenia in 1 patient (4.5%), grade 3 neutropenia in 1 patient (4.5%), grade 4 anemia in 1 patient (4.5%) and grade 3 nausea and anorexia in 1 patient (4.5%). CONCLUSIONS Pemetrexed maintenance therapy following initial pemetrexed and platinum chemotherapy improve PFS in patients with MPM, and is well tolerated.
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30
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Hajj GNM, Cavarson CH, Pinto CAL, Venturi G, Navarro JR, Lima VCCD. Malignant pleural mesothelioma: an update. J Bras Pneumol 2021; 47:e20210129. [PMID: 34909922 PMCID: PMC8836658 DOI: 10.36416/1806-3756/e20210129] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2021] [Accepted: 09/11/2021] [Indexed: 12/14/2022] Open
Abstract
Malignant mesotheliomas are rare types of cancers that affect the mesothelial surfaces, usually the pleura and peritoneum. They are associated with asbestos exposure, but due to a latency period of more than 30 years and difficult diagnosis, most cases are not detected until they reach advanced stages. Treatment options for this tumor type are very limited and survival ranges from 12 to 36 months. This review discusses the molecular physiopathology, current diagnosis, and latest therapeutic options for this disease.
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Affiliation(s)
- Glaucia N M Hajj
- Instituto International de Pesquisa, A.C. Camargo Cancer Center, São Paulo (SP), Brasil.,Instituto Nacional de Oncogenômica e Inovação Terapêutica, São Paulo (SP), Brasil
| | - Carolina H Cavarson
- Instituto International de Pesquisa, A.C. Camargo Cancer Center, São Paulo (SP), Brasil.,Instituto Nacional de Oncogenômica e Inovação Terapêutica, São Paulo (SP), Brasil
| | | | - Gabriela Venturi
- Instituto International de Pesquisa, A.C. Camargo Cancer Center, São Paulo (SP), Brasil.,BP Mirante, São Paulo (SP), Brasil
| | | | - Vladmir C Cordeiro de Lima
- Instituto Nacional de Oncogenômica e Inovação Terapêutica, São Paulo (SP), Brasil.,Rede D'Or, São Paulo (SP), Brasil
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31
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Otsubo K, Sakai H, Kimura H, Miyazawa T, Marushima H, Kojima K, Furuya N, Mineshita M, Chosokabe M, Koike J, Saji H. Thoracic mesenchymal malignant tumors and programed cell death ligand-1 status: Clinicopathologic and prognostic analysis of eight pulmonary sarcomatoid carcinomas and eight malignant mesotheliomas. Thorac Cancer 2021; 12:3169-3176. [PMID: 34655161 PMCID: PMC8636199 DOI: 10.1111/1759-7714.14177] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2021] [Revised: 09/14/2021] [Accepted: 09/16/2021] [Indexed: 11/28/2022] Open
Abstract
BACKGROUND The current study aimed to evaluate the significance of clinicopathological factors, particularly the immunohistochemistry of programed cell death ligand-1 (PD-L1), in eight cases each of pulmonary sarcomatoid carcinoma (PSC) and malignant pleural mesothelioma (MPM) at our hospital. METHODS From January 2004 to December 2020, a total of 16 consecutive patients (eight with PSC and eight with MPM diagnosed via surgical resection or biopsy) were included in this study. After retrospectively reviewing the patient characteristics, the associations between PD-L1 status and age, sex, stage, histological type, and prognosis were investigated. RESULTS PD-L1-positive staining was observed in four (50%) PSC cases and one (12.5%) MPM case. Among the four PD-L1-positive PSC cases, two showed high PD-L1 expression in the vimentin-positive sarcomatoid compartment. Moreover, among those with PSC, two survived for about 10 years, whereas the others died within 5 years. No clear correlation was found between PD-L1 expression and prognosis. Among the patients with MPM, four survived for more than 2 years, with the longest being 9 years. Among MPM cases who received nivolumab, one patient with positive PD-L1 staining in the sarcomatoid survived, whereas the other with negative PD-L1 staining did not. CONCLUSION The present study showed that sarcomatoid carcinoma had a higher PD-L1 expression compared to non-small-cell lung cancer and that both PSC and MPM tended to exhibit PD-L1 positivity in the sarcomatoid compartment. Moreover, while immune checkpoint inhibitors may somewhat prolong the prognosis of both tumors, further studies with a larger cohort are necessary to confirm our results.
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Affiliation(s)
- Kanji Otsubo
- Departments of Chest SurgerySt. Marianna University School of MedicineKawasakiJapan
| | - Hiroki Sakai
- Departments of Chest SurgerySt. Marianna University School of MedicineKawasakiJapan
| | - Hiroyuki Kimura
- Departments of Chest SurgerySt. Marianna University School of MedicineKawasakiJapan
| | - Tomoyuki Miyazawa
- Departments of Chest SurgerySt. Marianna University School of MedicineKawasakiJapan
| | - Hideki Marushima
- Departments of Chest SurgerySt. Marianna University School of MedicineKawasakiJapan
| | - Koji Kojima
- Departments of Chest SurgerySt. Marianna University School of MedicineKawasakiJapan
| | - Naoki Furuya
- Division of Respiratory Medicine, Department of Internal MedicineSt. Marianna University School of MedicineKawasakiJapan
| | - Masamichi Mineshita
- Division of Respiratory Medicine, Department of Internal MedicineSt. Marianna University School of MedicineKawasakiJapan
| | - Motohiro Chosokabe
- Department of PathologySt. Marianna University School of MedicineKawasakiJapan
| | - Junki Koike
- Department of PathologySt. Marianna University School of MedicineKawasakiJapan
| | - Hisashi Saji
- Departments of Chest SurgerySt. Marianna University School of MedicineKawasakiJapan
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Filetti V, Loreto C, Falzone L, Lombardo C, Cannizzaro E, Castorina S, Ledda C, Rapisarda V. Diagnostic and Prognostic Value of Three microRNAs in Environmental Asbestiform Fibers-Associated Malignant Mesothelioma. J Pers Med 2021; 11:jpm11111205. [PMID: 34834557 PMCID: PMC8618926 DOI: 10.3390/jpm11111205] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2021] [Revised: 11/08/2021] [Accepted: 11/11/2021] [Indexed: 12/17/2022] Open
Abstract
Fluoro-edenite (FE) is an asbestiform fiber identified in Biancavilla (Sicily, Italy). Environmental exposure to FE has been associated with a higher incidence of malignant mesothelioma (MM). The present study aimed to validate the predicted diagnostic significance of hsa-miR-323a-3p, hsa-miR-101-3p, and hsa-miR-20b-5p on a subset of MM patients exposed to FE and matched with healthy controls. For this purpose, MM tissues vs. nonmalignant pleura tissues were analyzed through droplet digital PCR (ddPCR) to evaluate differences in the expression levels of the selected miRNAs and their MM diagnostic potential. In addition, further computational analysis has been performed to establish the correlation of these miRNAs with the available online asbestos exposure data and clinic-pathological parameters to verify the potential role of these miRNAs as prognostic tools. ddPCR results showed that the three analyzed miRNAs were significantly down-regulated in MM cases vs. controls. Receiver operating characteristic (ROC) analysis revealed high specificity and sensitivity rates for both hsa-miR-323a-3p and hsa-miR-20b-5p, which thus acquire a diagnostic value for MM. In silico results showed a potential prognostic role of hsa-miR-101-3p due to a significant association of its higher expression and increased overall survival (OS) of MM patients.
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Affiliation(s)
- Veronica Filetti
- Human Anatomy and Histology, Department of Biomedical and Biotechnology Sciences, University of Catania, 95123 Catania, Italy; (V.F.); (C.L.)
| | - Carla Loreto
- Human Anatomy and Histology, Department of Biomedical and Biotechnology Sciences, University of Catania, 95123 Catania, Italy; (V.F.); (C.L.)
| | - Luca Falzone
- Epidemiology Unit, IRCCS Istituto Nazionale Tumori “Fondazione G. Pascale”, 80131 Naples, Italy;
| | - Claudia Lombardo
- Human Anatomy, Department of Medical and Surgical Sciences and Advanced Technologies, University of Catania, 95123 Catania, Italy; (C.L.); (S.C.)
| | - Emanuele Cannizzaro
- Occupational Medicine, Department of Sciences for Health Promotion and Mother and Child Care, University of Palermo, 90128 Palermo, Italy;
| | - Sergio Castorina
- Human Anatomy, Department of Medical and Surgical Sciences and Advanced Technologies, University of Catania, 95123 Catania, Italy; (C.L.); (S.C.)
| | - Caterina Ledda
- Occupational Medicine, Department of Clinical and Experimental Medicine, University of Catania, Via Santa Sofia 87, 95123 Catania, Italy;
- Correspondence:
| | - Venerando Rapisarda
- Occupational Medicine, Department of Clinical and Experimental Medicine, University of Catania, Via Santa Sofia 87, 95123 Catania, Italy;
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Hemminki K, Försti A, Chen T, Hemminki A. Incidence, mortality and survival in malignant pleural mesothelioma before and after asbestos in Denmark, Finland, Norway and Sweden. BMC Cancer 2021; 21:1189. [PMID: 34749677 PMCID: PMC8576876 DOI: 10.1186/s12885-021-08913-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2021] [Accepted: 10/20/2021] [Indexed: 11/22/2022] Open
Abstract
Background Malignant pleural mesothelioma (MPM) is a rare but fatal cancer, which is largely caused by exposure to asbestos. Reliable information about the incidence of MPM prior the influence of asbestos is lacking. The nationwide regional incidence trends for MPM remain poorly characterized. We use nationwide MPM data for Denmark (DK), Finland (FI), Norway (NO) and Sweden (SE) to assess incidence, mortality and survival trends for MPM in these countries. Methods We use the NORDCAN database for the analyses: incidence data were available from 1943 in DK, 1953 in FI and NO and 1958 in SE, through 2016. Survival data were available from 1967 through 2016. World standard population was used in age standardization. Results The lowest incidence that we recorded for MPM was 0.02/100,000 for NO women and 0.05/100,000 for FI men in 1953–57, marking the incidence before the influence of asbestos. The highest rate of 1.9/100,000 was recorded for DK in 1997. Female incidence was much lower than male incidence. In each country, the male incidence trend for MPM culminated, first in SE around 1990. The regional incidence trends matched with earlier asbestos-related industrial activity, shipbuilding in FI and SE, cement manufacturing and shipbuilding in DK and seafaring in NO. Relative 1-year survival increased from about 20 to 50% but 5-year survival remained at or below 10%. Conclusion In the Nordic countries, the male incidence trends for MPM climaxed and started to decrease, indicating that the prevention of exposure was beneficial. Survival in MPM has improved for both sexes but long-term survival remains dismal. Supplementary Information The online version contains supplementary material available at 10.1186/s12885-021-08913-2.
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Affiliation(s)
- Kari Hemminki
- Biomedical Center, Faculty of Medicine and Biomedical Center in Pilsen, Charles University in Prague, 30605, Pilsen, Czech Republic. .,Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 580, D-69120, Heidelberg, Germany.
| | - Asta Försti
- Hopp Children's Cancer Center (KiTZ), Heidelberg, Germany.,Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), Heidelberg, Germany
| | - Tianhui Chen
- Department of Cancer Prevention/Zhejiang Cancer Institute, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer, Chinese Academy of Sciences, Hangzhou, 310022, China.
| | - Akseli Hemminki
- Cancer Gene Therapy Group, Translational Immunology Research Program, University of Helsinki, Helsinki, Finland.,Comprehensive Cancer Center, Helsinki University Hospital, Helsinki, Finland
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34
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Zolondick AA, Gaudino G, Xue J, Pass HI, Carbone M, Yang H. Asbestos-induced chronic inflammation in malignant pleural mesothelioma and related therapeutic approaches-a narrative review. PRECISION CANCER MEDICINE 2021; 4. [PMID: 35098108 PMCID: PMC8797751 DOI: 10.21037/pcm-21-12] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Objective: The aim of this review is addressing the mechanisms of asbestos carcinogenesis, including chronic inflammation and autophagy-mediated cell survival, and propose potential innovative therapeutic targets to prevent mesothelioma development or improve drug efficacy by reducing inflammation and autophagy. Background: Diffuse malignant pleural mesothelioma is an aggressive cancer predominantly related to chronic inflammation caused by asbestos exposure. Millions of individuals have been exposed to asbestos or to other carcinogenic mineral fibers occupationally or environmentally, resulting in an increased risk of developing mesothelioma. Overall patient survival rates are notably low (about 8–14 months from the time of diagnosis) and mesothelioma is resistant to existing therapies. Additionally, individuals carrying inactivating germline mutations in the BRCA-associated protein 1 (BAP1) gene and other genes are predisposed to developing cancers, prevalently mesothelioma. Their risk of developing mesothelioma further increases upon exposure to asbestos. Recent studies have revealed the mechanisms and the role of inflammation in asbestos carcinogenesis. Biomarkers for asbestos exposure and malignant mesothelioma have also been identified. These findings are leading to the development of novel therapeutic approaches to prevent or delay the growth of mesothelioma. Methods: Review of full length manuscripts published in English from January 1980 to February 2021 gathered from PubMed.gov from the National Center of Biotechnology Information and the National Library of Medicine were used to inform this review. Conclusion: Key regulators of chronic inflammation mediate asbestos-driven mesothelial cell transformation and survival through autophagic pathways. Recent studies have elucidated some of the key mechanisms involved in asbestos-induced chronic inflammation, which are largely driven by extracellular high mobility group box 1 (HMGB1). Upon asbestos exposure, mesothelial cells release HMGB1 from the nucleus to the cytoplasm and extracellular space, where HMGB1 initiates an inflammatory response. HMGB1 translocation and release also activates autophagy and other pro-survival mechanisms, which promotes mesothelioma development. HMGB1 is currently being investigated as a biomarker to detect asbestos exposure and to detect mesothelioma development in its early stage when therapy is more effective. In parallel, several approaches inhibiting HMGB1 activities have been studied and have shown promising results. Moreover, additional cytokines, such as IL-1β and TNF-α are being targeted to interfere with the inflammatory process that drives mesothelioma growth. Developing early detection methods and novel therapeutic strategies is crucial to prolong overall survival of patients with mesothelioma. Novel therapies targeting regulators of asbestos-induced inflammation to reduce mesothelioma growth may lead to clinical advancements to benefit patients with mesothelioma.
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Affiliation(s)
- Alicia A Zolondick
- University of Hawai'i Cancer Center, Honolulu, HI, USA.,Department of Molecular Biosciences and Bioengineering, University of Hawai'i at Manoa, Honolulu, HI, USA
| | | | - Jiaming Xue
- University of Hawai'i Cancer Center, Honolulu, HI, USA.,University of Hawai'i, John A. Burns School of Medicine, Honolulu, HI, USA
| | - Harvey I Pass
- Department of Cardiothoracic Surgery, New York University Langone Medical Center, New York, NY, USA
| | | | - Haining Yang
- University of Hawai'i Cancer Center, Honolulu, HI, USA
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Romei C, Fanni SC, Volpi F, Milazzo A, D’Amore CA, Colligiani L, Neri E, De Liperi A, Stella GM, Bortolotto C. New Updates of the Imaging Role in Diagnosis, Staging, and Response Treatment of Malignant Pleural Mesothelioma. Cancers (Basel) 2021; 13:cancers13174377. [PMID: 34503186 PMCID: PMC8430786 DOI: 10.3390/cancers13174377] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2021] [Revised: 08/24/2021] [Accepted: 08/27/2021] [Indexed: 11/16/2022] Open
Abstract
Malignant pleural mesothelioma is a rare neoplasm with poor prognosis. CT is the first imaging technique used for diagnosis, staging, and assessment of therapy response. Although, CT has intrinsic limitations due to low soft tissue contrast and the current staging system as well as criteria for evaluating response, it does not consider the complex growth pattern of this tumor. Computer-based methods have proven their potentiality in diagnosis, staging, prognosis, and assessment of therapy response; moreover, computer-based methods can make feasible tasks like segmentation that would otherwise be impracticable. MRI, thanks to its high soft tissue contrast evaluation of contrast enhancement and through diffusion-weighted-images, could replace CT in many clinical settings.
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Affiliation(s)
- Chiara Romei
- 2nd Radiology Unit, Radiology Department, Pisa University Hospital, 56124 Pisa, Italy;
- Correspondence: (C.R.); (S.C.F.)
| | - Salvatore Claudio Fanni
- Department of Translational Research, Academic Radiology, University of Pisa, 56124 Pisa, Italy; (F.V.); (A.M.); (C.A.D.); (L.C.); (E.N.)
- Correspondence: (C.R.); (S.C.F.)
| | - Federica Volpi
- Department of Translational Research, Academic Radiology, University of Pisa, 56124 Pisa, Italy; (F.V.); (A.M.); (C.A.D.); (L.C.); (E.N.)
| | - Alessio Milazzo
- Department of Translational Research, Academic Radiology, University of Pisa, 56124 Pisa, Italy; (F.V.); (A.M.); (C.A.D.); (L.C.); (E.N.)
| | - Caterina Aida D’Amore
- Department of Translational Research, Academic Radiology, University of Pisa, 56124 Pisa, Italy; (F.V.); (A.M.); (C.A.D.); (L.C.); (E.N.)
| | - Leonardo Colligiani
- Department of Translational Research, Academic Radiology, University of Pisa, 56124 Pisa, Italy; (F.V.); (A.M.); (C.A.D.); (L.C.); (E.N.)
| | - Emanuele Neri
- Department of Translational Research, Academic Radiology, University of Pisa, 56124 Pisa, Italy; (F.V.); (A.M.); (C.A.D.); (L.C.); (E.N.)
| | - Annalisa De Liperi
- 2nd Radiology Unit, Radiology Department, Pisa University Hospital, 56124 Pisa, Italy;
| | - Giulia Maria Stella
- Unit of Respiratory Diseases, Department of Medical Sciences and Infective Diseases, IRCCS Policlinico San Matteo Foundation, University of Pavia Medical School, 27100 Pavia, Italy;
| | - Chandra Bortolotto
- Unit of Radiology, Department of Intensive Medicine, IRCCS Policlinico San Matteo Foundation, University of Pavia Medical School, 27100 Pavia, Italy;
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36
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Brims F. Epidemiology and Clinical Aspects of Malignant Pleural Mesothelioma. Cancers (Basel) 2021; 13:cancers13164194. [PMID: 34439349 PMCID: PMC8391310 DOI: 10.3390/cancers13164194] [Citation(s) in RCA: 35] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2021] [Revised: 08/12/2021] [Accepted: 08/19/2021] [Indexed: 02/06/2023] Open
Abstract
Mesothelioma is a cancer predominantly of the pleural cavity. There is a clear association of exposure to asbestos with a dose dependent risk of mesothelioma. The incidence of mesothelioma in different countries reflect the historical patterns of commercial asbestos utilisation in the last century and predominant occupational exposures mean that mesothelioma is mostly seen in males. Modern imaging techniques and advances in immunohistochemical staining have contributed to an improved diagnosis of mesothelioma. There have also been recent advances in immune checkpoint inhibition, however, mesothelioma remains very challenging to manage, especially considering its limited response to conventional systemic anticancer therapy and that no cure exists. Palliative interventions and support remain paramount with a median survival of 9-12 months after diagnosis. The epidemiology and diagnosis of mesothelioma has been debated over previous decades, due to a number of factors, such as the long latent period following asbestos exposure and disease occurrence, the different potencies of the various forms of asbestos used commercially, the occurrence of mesothelioma in the peritoneal cavity and its heterogeneous pathological and cytological appearances. This review will describe the contemporary knowledge on the epidemiology of mesothelioma and provide an overview of the best clinical practice including diagnostic approaches and management.
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Affiliation(s)
- Fraser Brims
- Curtin Medical School, Curtin University, Perth, WA 6845, Australia;
- Department of Respiratory Medicine, Sir Charles Gairdner Hospital, Perth, WA 6009, Australia
- National Centre for Asbestos Related Diseases, Institute for Respiratory Health, Perth, WA 6009, Australia
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Napoli F, Listì A, Zambelli V, Witel G, Bironzo P, Papotti M, Volante M, Scagliotti G, Righi L. Pathological Characterization of Tumor Immune Microenvironment (TIME) in Malignant Pleural Mesothelioma. Cancers (Basel) 2021; 13:2564. [PMID: 34073720 PMCID: PMC8197227 DOI: 10.3390/cancers13112564] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2021] [Revised: 05/17/2021] [Accepted: 05/19/2021] [Indexed: 02/08/2023] Open
Abstract
Malignant pleural mesothelioma (MPM) is a rare and highly aggressive disease that arises from pleural mesothelial cells, characterized by a median survival of approximately 13-15 months after diagnosis. The primary cause of this disease is asbestos exposure and the main issues associated with it are late diagnosis and lack of effective therapies. Asbestos-induced cellular damage is associated with the generation of an inflammatory microenvironment that influences and supports tumor growth, possibly in association with patients' genetic predisposition and tumor genomic profile. The chronic inflammatory response to asbestos fibers leads to a unique tumor immune microenvironment (TIME) composed of a heterogeneous mixture of stromal, endothelial, and immune cells, and relative composition and interaction among them is suggested to bear prognostic and therapeutic implications. TIME in MPM is known to be constituted by immunosuppressive cells, such as type 2 tumor-associated macrophages and T regulatory lymphocytes, plus the expression of several immunosuppressive factors, such as tumor-associated PD-L1. Several studies in recent years have contributed to achieve a greater understanding of the pathogenetic mechanisms in tumor development and pathobiology of TIME, that opens the way to new therapeutic strategies. The study of TIME is fundamental in identifying appropriate prognostic and predictive tissue biomarkers. In the present review, we summarize the current knowledge about the pathological characterization of TIME in MPM.
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Affiliation(s)
- Francesca Napoli
- Department of Oncology, University of Turin, 10043 Orbassano, Italy; (F.N.); (V.Z.); (P.B.); (M.P.); (M.V.); (G.S.)
| | - Angela Listì
- Thoracic Oncology Unit, San Luigi Hospital, 10043 Orbassano, Italy;
| | - Vanessa Zambelli
- Department of Oncology, University of Turin, 10043 Orbassano, Italy; (F.N.); (V.Z.); (P.B.); (M.P.); (M.V.); (G.S.)
| | - Gianluca Witel
- Department of Medical Sciences, University of Turin, City of Health and Science, 10126 Torino, Italy;
| | - Paolo Bironzo
- Department of Oncology, University of Turin, 10043 Orbassano, Italy; (F.N.); (V.Z.); (P.B.); (M.P.); (M.V.); (G.S.)
- Thoracic Oncology Unit, San Luigi Hospital, 10043 Orbassano, Italy;
| | - Mauro Papotti
- Department of Oncology, University of Turin, 10043 Orbassano, Italy; (F.N.); (V.Z.); (P.B.); (M.P.); (M.V.); (G.S.)
- Pathology Unit, City of Health and Science, 10126 Torino, Italy
| | - Marco Volante
- Department of Oncology, University of Turin, 10043 Orbassano, Italy; (F.N.); (V.Z.); (P.B.); (M.P.); (M.V.); (G.S.)
| | - Giorgio Scagliotti
- Department of Oncology, University of Turin, 10043 Orbassano, Italy; (F.N.); (V.Z.); (P.B.); (M.P.); (M.V.); (G.S.)
- Thoracic Oncology Unit, San Luigi Hospital, 10043 Orbassano, Italy;
| | - Luisella Righi
- Department of Oncology, University of Turin, 10043 Orbassano, Italy; (F.N.); (V.Z.); (P.B.); (M.P.); (M.V.); (G.S.)
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Wilk E, Krówczyńska M. Malignant mesothelioma and asbestos exposure in Europe: Evidence of spatial clustering. GEOSPATIAL HEALTH 2021; 16. [PMID: 34000787 DOI: 10.4081/gh.2021.951] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/13/2020] [Accepted: 02/25/2021] [Indexed: 06/12/2023]
Abstract
Exposure to asbestos causes a wide range of diseases, such as asbestosis, malignant mesothelioma (MM) and other types of cancer. Many European countries have reduced production and use of asbestos and some have banned it altogether. Based on data derived from the World Health Organisation (WHO) Cancer Mortality Database, we investigated whether some regions in Europe could have a higher relative risk of MM incidence than others. The data were compared, including the number of MM deaths per million inhabitants and aged-standardized mortality rates. Applying Moran's I and Getis-Ord Gi statistic on the agedstandardized mortality rates of MM cases assisted the spatial analysis of the occurrence of health events leading to an assessment of the heterogeneity of distribution and cluster detection of MM. We found a statistically significant positive autocorrelation for the male population and also the general population, while there was no statistically significant positive one for the female population. Hotspots of relative risk of developing MM were found in northwestern Europe. For the general population, Great Britain and the Netherlands stood out with high levels at the 99% and 95% confidence levels, respectively. For the male population, the results were similar, but with addition of risk also in Belgium and Switzerland. However, in many European countries with high asbestos use per capita, the MM incidence was found to still be low. The reasons for this are not yet clear, but part of the problem is certainly due to incomplete data in registers and databases. The latency time can be longer than 40 years and is related to the intensity and time of exposure (occupational, para-occupational and environmental). In Europe, even though peak production occurred in the 1960s and 1970s, a significant decrease in production did not occur until 25 years later, which means that the impact will continue for as late as The mid 2030s.
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Affiliation(s)
- Ewa Wilk
- Department of Geoinformatics, Cartography and Remote Sensing, Faculty of Geography and Regional Studies, University of Warsaw, Warsaw.
| | - Małgorzata Krówczyńska
- Department of Geoinformatics, Cartography and Remote Sensing, Faculty of Geography and Regional Studies, University of Warsaw, Warsaw.
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Reid G, Klebe S, van Zandwijk N, George AM. Asbestos and Zeolites: from A to Z via a Common Ion. Chem Res Toxicol 2021; 34:936-951. [PMID: 33749247 DOI: 10.1021/acs.chemrestox.0c00286] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
Asbestos and zeolites are silicate-based minerals, linked inextricably via paradoxical similarities and differences which have emanated from different geological epochs. Both have been employed in the service of humanity through millennia: asbestos, for its "inextinguishable" quality of being an insulator against heat and fire; zeolite, a "boiling stone" with its volcanic and marine sedimentary rock origins, for its propensity to adsorb water and remove metals and toxins. Serious adverse health effects observed in asbestos miners as long ago as the 1st Century AD did not halt the rising popularity of asbestos. As the miracle material of the 1900s, asbestos production and consumption exploded, culminating in its ubiquity in ships, vehicles, homes, commercial buildings, and over 3000 different industrial and household products. Through the 1940s and 1950s, epidemiological studies concluded that asbestos was a likely cause of asbestosis, lung cancer, and malignant mesothelioma, and it is now banned in many but far from all countries. The long latency between exposure to asbestos and the occurrence of cancer has obscured the deadly consequences of asbestos exposure for centuries. Even today, a considerable part of the world population is insufficiently aware of the dangers of asbestos, and millions of tons of this carcinogen continue to be mined and used worldwide. Zeolites, both natural and synthetic, are microporous aluminosilicate minerals commonly used in a myriad of processes, in the petrochemical industry, in domestic appliances and cleaning agents, as commercial adsorbents and exchangers for toxins and pollutants, and as catalysts. Zeolites are found in agriculture, veterinary science, and human health. More recently, new materials such as carbon nanotubes are being employed in materials requiring durability and thermal and electrical conductivity, yet nanotubes are now joining the ranks of more established particulates such as asbestos and silica, in causing human disease. In this review, we compare and contrast the similarities and differences of these two groups of silicate minerals and their waxing and waning use in the employ of humanity.
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Affiliation(s)
- Glen Reid
- Department of Pathology, Dunedin School of Medicine, University of Otago, P.O. Box 56, Dunedin 9054, New Zealand
| | - Sonja Klebe
- Department of Anatomical Pathology, Flinders University and SA Pathology Bedford Park 5042, Australia
| | - Nico van Zandwijk
- Sydney Local Health District, Concord Repatriation General Hospital, Concord, New South Wales 2139, Australia
| | - Anthony M George
- School of Life Sciences, University of Technology Sydney, P.O. Box 123 Broadway, New South Wales 2007, Australia
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Identification of distinct immune landscapes using an automated nine-color multiplex immunofluorescence staining panel and image analysis in paraffin tumor tissues. Sci Rep 2021; 11:4530. [PMID: 33633208 PMCID: PMC7907283 DOI: 10.1038/s41598-021-83858-x] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2020] [Accepted: 01/20/2021] [Indexed: 12/15/2022] Open
Abstract
Immune profiling is becoming a vital tool for identifying predictive and prognostic markers for translational studies. The study of the tumor microenvironment (TME) in paraffin tumor tissues such as malignant pleural mesothelioma (MPM) could yield insights to actionable targets to improve patient outcome. Here, we optimized and tested a new immune-profiling method to characterize immune cell phenotypes in paraffin tissues and explore the co-localization and spatial distribution between the immune cells within the TME and the stromal or tumor compartments. Tonsil tissues and tissue microarray (TMA) were used to optimize an automated nine-color multiplex immunofluorescence (mIF) panel to study the TME using eight antibodies: PD-L1, PD-1, CD3, CD8, Foxp3, CD68, KI67, and pancytokeratin. To explore the potential role of the cells into the TME with this mIF panel we applied this panel in twelve MPM cases to assess the multiple cell phenotypes obtained from the image analysis and well as their spatial distribution in this cohort. We successful optimized and applied an automated nine-color mIF panel to explore a small set of MPM cases. Image analysis showed a high degree of cell phenotype diversity with immunosuppression patterns in the TME of the MPM cases. Mapping the geographic cell phenotype distribution in the TME, we were able to identify two distinct, complex immune landscapes characterized by specific patterns of cellular distribution as well as cell phenotype interactions with malignant cells. Successful we showed the optimization and reproducibility of our mIF panel and their incorporation for comprehensive TME immune profiling into translational studies that could refine our ability to correlate immunologic phenotypes with specific patterns of cells distribution and distance analysis. Overall, this will improve our ability to understand the behavior of cells within the TME and predict new treatment strategies to improve patient outcome.
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Denzler S, Vuong D, Bogowicz M, Pavic M, Frauenfelder T, Thierstein S, Eboulet EI, Maurer B, Schniering J, Gabryś HS, Schmitt-Opitz I, Pless M, Foerster R, Guckenberger M, Tanadini-Lang S. Impact of CT convolution kernel on robustness of radiomic features for different lung diseases and tissue types. Br J Radiol 2021; 94:20200947. [PMID: 33544646 DOI: 10.1259/bjr.20200947] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
OBJECTIVES In this study, we aimed to assess the impact of different CT reconstruction kernels on the stability of radiomic features and the transferability between different diseases and tissue types. Three lung diseases were evaluated, i.e. non-small cell lung cancer (NSCLC), malignant pleural mesothelioma (MPM) and interstitial lung disease related to systemic sclerosis (SSc-ILD) as well as four different tissue types, i.e. primary tumor, largest involved lymph node ipsilateral and contralateral lung. METHODS Pre-treatment non-contrast enhanced CT scans from 23 NSCLC, 10 MPM and 12 SSc-ILD patients were collected retrospectively. For each patient, CT scans were reconstructed using smooth and sharp kernel in filtered back projection. The regions of interest (ROIs) were contoured on the smooth kernel-based CT and transferred to the sharp kernel-based CT. The voxels were resized to the largest voxel dimension of each cohort. In total, 1386 features were analyzed. Feature stability was assessed using the intraclass correlation coefficient. Features above the stability threshold >0.9 were considered stable. RESULTS We observed a strong impact of the reconstruction method on stability of the features (at maximum 26% of the 1386 features were stable). Intensity features were the most stable followed by texture and wavelet features. The wavelet features showed a positive correlation between percentage of stable features and size of the ROI (R2 = 0.79, p = 0.005). Lymph node radiomics showed poorest stability (<10%) and lung radiomics the largest stability (26%). Robustness analysis done on the contralateral lung could to a large extent be transferred to the ipsilateral lung, and the overlap of stable lung features between different lung diseases was more than 50%. However, results of robustness studies cannot be transferred between tissue types, which was investigated in NSCLC and MPM patients; the overlap of stable features for lymph node and lung, as well as for primary tumor and lymph node was very small in both disease types. CONCLUSION The robustness of radiomic features is strongly affected by different reconstruction kernels. The effect is largely influenced by the tissue type and less by the disease type. ADVANCES IN KNOWLEDGE The study presents to our knowledge the most complete analysis on the impact of convolution kernel on the robustness of CT-based radiomics for four relevant tissue types in three different lung diseases. .
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Affiliation(s)
- Sarah Denzler
- Department of Radiation Oncology, University Hospital Zurich and University of Zurich, Zurich, Switzerland
| | - Diem Vuong
- Department of Radiation Oncology, University Hospital Zurich and University of Zurich, Zurich, Switzerland
| | - Marta Bogowicz
- Department of Radiation Oncology, University Hospital Zurich and University of Zurich, Zurich, Switzerland
| | - Matea Pavic
- Department of Radiation Oncology, University Hospital Zurich and University of Zurich, Zurich, Switzerland
| | - Thomas Frauenfelder
- Institute of Diagnostic and Interventional Radiology, University Hospital Zurich and University of Zurich, Zurich, Switzerland
| | | | | | - Britta Maurer
- Department of Rheumatology, Center of Experimental Rheumatology, University Hospital Zurich and University of Zurich, Zurich, Switzerland
| | - Janine Schniering
- Department of Rheumatology, Center of Experimental Rheumatology, University Hospital Zurich and University of Zurich, Zurich, Switzerland
| | - Hubert Szymon Gabryś
- Department of Radiation Oncology, University Hospital Zurich and University of Zurich, Zurich, Switzerland
| | - Isabelle Schmitt-Opitz
- Department of Thoracic Surgery, University Hospital Zurich and University of Zurich, Zurich, Switzerland
| | - Miklos Pless
- Department of Medical Oncology, Kantonsspital Winterthur, Winterthur, Switzerland
| | - Robert Foerster
- Department of Radiation Oncology, University Hospital Zurich and University of Zurich, Zurich, Switzerland
| | - Matthias Guckenberger
- Department of Radiation Oncology, University Hospital Zurich and University of Zurich, Zurich, Switzerland
| | - Stephanie Tanadini-Lang
- Department of Radiation Oncology, University Hospital Zurich and University of Zurich, Zurich, Switzerland
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A preliminary study: is fibulin 1 a friend or an enemy that needs to be silenced with siRNAs for mesothelioma? Contemp Oncol (Pozn) 2021; 24:241-246. [PMID: 33531871 PMCID: PMC7836276 DOI: 10.5114/wo.2020.102826] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2020] [Accepted: 10/22/2020] [Indexed: 01/22/2023] Open
Abstract
Introduction The impaired balance between cell proliferation and cell death, followed the inability to receive the death signals, cells push towards the neoplasia pathway. Fibulin 1 (FBLN1) plays a role as a co-factor in the mechanism of action of a protease such as a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS-1), which has important roles in angiogenesis, can also act as both tumor suppressor gene (TSG) and an oncogene in the main constituent of the extra-cellular matrix. This preliminary study has investigated the effects of silencing FBLN1 with siRNA on autophagy, proliferation, apoptosis pathways in the MSM cell line. Material and methods It was transfected siRNA specific to FBLN1 incubated MSM SPC212 cells, and compared with negative control siRNAs by a real-time polymerase chain reaction. It was determined apoptosis, proliferation, autophagy-related genes in mRNA levels. Results It was observed that increased anti-apoptosis genes, such as CASP2, CASP7, DDFA, and BCL2, anti-apoptotic gene, reduced APAF1, CASP8. Proliferation induced through while increased ADAMTS1, CDH1, CDH6, CLDN7, CSF3, MMP7, MMP13 genes. Autophagy increased via increasing MAP1LC3B, ATG-16L1 genes while decreased via suppressed ULK1, and ATG7 genes by silencing FBLN1 with siRNAs (p < 0.05). Conclusions Proliferation can be induction with silencing of FBLN1 with siRNA in processing mechanism MSM. It was concluded that FBLN1 could be act as pleiotropic on autophagy, and apoptosis pathways in proliferation processing for MSM. Therefore we think that FBLN1 acts like a TSG. FBLN1 can be considered as a targeted treatment option in advanced stage MSM.
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Slomovitz B, de Haydu C, Taub M, Coleman RL, Monk BJ. Asbestos and ovarian cancer: examining the historical evidence. Int J Gynecol Cancer 2021; 31:122-128. [PMID: 33037108 DOI: 10.1136/ijgc-2020-001672] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2020] [Revised: 09/09/2020] [Accepted: 09/11/2020] [Indexed: 12/15/2022] Open
Abstract
Asbestos recently returned to the spotlight when Johnson & Johnson halted sales of baby powder due to lawsuits claiming that the talc in baby powder may have been contaminated with asbestos, which has been linked to the risk of ovarian cancer development. Although talc and asbestos have some structural similarities, only asbestos is considered causally associated with ovarian cancer by the WHO's International Agency for Research on Cancer. While it is useful to understand the types and properties of asbestos and its oncologic biology, the history of its association with ovarian cancer is largely based on retrospective observational studies in women working in high asbestos exposure environments. In reviewing the literature, it is critical to understand the distinction between associative risk and causality, and to examine the strength of association in the context of how the diagnosis of ovarian cancer is made and how the disease should be distinguished from a similar appearing but unrelated neoplasm, malignant mesothelioma. Based on contextual misinterpretation of these factors, it is imperative to question the International Agency for Research on Cancer's assertion that asbestos has a clear causal inference to ovarian cancer. This has important clinical implications in the way patients are conceivably counseled and provides motivation to continue research to improve the understanding of the association between asbestos and ovarian cancer.
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Affiliation(s)
- Brian Slomovitz
- Gynecologic Oncology, Broward Health, Fort Lauderdale, Florida, USA
- Obstetrics and Gynecology, Florida International University Herbert Wertheim College of Medicine, Miami, Florida, USA
| | - Christopher de Haydu
- Division of Gynecologic Oncology of the Department of Obstetrics, Gynecology, & Reproductive Sciences, No Affiliation, Miami, Florida, USA
| | - Michael Taub
- Stony Brook University, Stony Brook, New York, USA
| | | | - Bradley J Monk
- Gynecologic Oncology, Obstetrics and Gynecology, Arizona Oncology (US Oncology Network), Phoenix, Arizona, USA
- Gynecologic Oncology, Obstetrics and Gynecology, Creighton University School of Medicine Phoenix Regional Campus, Phoenix, Arizona, USA
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The Crosstalk between FAK and Wnt Signaling Pathways in Cancer and Its Therapeutic Implication. Int J Mol Sci 2020; 21:ijms21239107. [PMID: 33266025 PMCID: PMC7730291 DOI: 10.3390/ijms21239107] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2020] [Revised: 11/24/2020] [Accepted: 11/26/2020] [Indexed: 12/12/2022] Open
Abstract
Focal adhesion kinase (FAK) and Wnt signaling pathways are important contributors to tumorigenesis in several cancers. While most results come from studies investigating these pathways individually, there is increasing evidence of a functional crosstalk between both signaling pathways during development and tumor progression. A number of FAK-Wnt interactions are described, suggesting an intricate, context-specific, and cell type-dependent relationship. During development for instance, FAK acts mainly upstream of Wnt signaling; and although in intestinal homeostasis and mucosal regeneration Wnt seems to function upstream of FAK signaling, FAK activates the Wnt/β-catenin signaling pathway during APC-driven intestinal tumorigenesis. In breast, lung, and pancreatic cancers, FAK is reported to modulate the Wnt signaling pathway, while in prostate cancer, FAK is downstream of Wnt. In malignant mesothelioma, FAK and Wnt show an antagonistic relationship: Inhibiting FAK signaling activates the Wnt pathway and vice versa. As the identification of effective Wnt inhibitors to translate in the clinical setting remains an outstanding challenge, further understanding of the functional interaction between Wnt and FAK could reveal new therapeutic opportunities and approaches greatly needed in clinical oncology. In this review, we summarize some of the most relevant interactions between FAK and Wnt in different cancers, address the current landscape of Wnt- and FAK-targeted therapies in different clinical trials, and discuss the rationale for targeting the FAK-Wnt crosstalk, along with the possible translational implications.
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Gandhi M, Nair S. New vistas in malignant mesothelioma: MicroRNA architecture and NRF2/MAPK signal transduction. Life Sci 2020; 257:118123. [PMID: 32710945 DOI: 10.1016/j.lfs.2020.118123] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2020] [Revised: 07/11/2020] [Accepted: 07/16/2020] [Indexed: 12/11/2022]
Abstract
Malignant mesothelioma (MM) is a cancer of the mesothelial lining of the pleura, peritoneum, pericardium and testes. The most common form is asbestos-linked MM that is etiologically linked to repeated asbestos exposure with a long latency period, although non-asbestos MM has also been reported. Late diagnosis, poor survival rates, lack of diagnostic and prognostic markers act as major impediments in the clinical management of MM. Despite advances in immune checkpoint inhibition and CAR T-cell-based therapies, MM which is of different histologic subtypes remains challenging to treat. We review microRNAs (miRNAs) and the miRNA interactome implicated in MM which can be useful as circulating miRNA biomarkers for early diagnosis of MM and as biomarkers for prognostication in MM. Further, we underscore the relevance of the NRF2/MAPK signal transduction pathway that has been implicated in MM which may be useful as druggable targets or as biomarkers of predictive response. In addition, since MM is driven partly by inflammation, we elucidate chemopreventive phytochemicals that are beneficial in MM, either via crosstalk with the NRF2/MAPK pathway or via concerted anticancer mechanisms, and may be of benefit as adjuvants in chemotherapy. Taken together, a multifactorial approach comprising identification of miRNA target hubs and NRF2/MAPK biomarkers along with appropriately designed clinical trials may enable early detection and faster intervention in MM translating into better patient outcomes for this aggressive cancer.
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Affiliation(s)
- Manav Gandhi
- SVKM's Dr. Bhanuben Nanavati College of Pharmacy, University of Mumbai, VL Mehta Road, Vile Parle (West), Mumbai 400 056, India
| | - Sujit Nair
- SVKM's Dr. Bhanuben Nanavati College of Pharmacy, University of Mumbai, VL Mehta Road, Vile Parle (West), Mumbai 400 056, India.
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Abstract
BACKGROUND Mesothelioma is a rare and deadly form of cancer, linked to asbestos exposure. Although the United Kingdom has banned asbestos, the incidence rate remains high. Previous research has indicated that female individuals have better survival than male individuals, but this has never been examined in the United Kingdom. MATERIALS AND METHODS Pleural mesothelioma cases from 2005 to 2014 were extracted from the United Kingdom Lung Cancer Dataset. Multivariable logistic regression was used to assess the clinical and demographic factors associated with gender. A multivariable Cox proportional hazards model and propensity matching methods were used to assess gender differences in overall survival while accounting for potential confounders. RESULTS There were 8479 (87.8%) male and 1765 (17.2%) female individuals included in the analysis. Female individuals were significantly younger, with more epithelial histology than male individuals. Female individuals had significantly better overall survival (adjusted hazard ratio, 0.85, 95% confidence interval, 0.81-0.90). Results remained similar when stratifying by age and performance status, and when limiting to patients with epithelial histology. CONCLUSIONS The study increases knowledge about gender differences in mesothelioma survival and is the first to directly examine this in the United Kingdom. It further disentangles the effects of age, histology, and health status. Increased estrogen may improve survival and could provide a potential target for future therapies.
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Klampatsa A, Albelda SM. Current Advances in CAR T Cell Therapy for Malignant Mesothelioma. JOURNAL OF CELLULAR IMMUNOLOGY 2020; 2:192-200. [PMID: 32914147 PMCID: PMC7480947 DOI: 10.33696/immunology.2.042] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
Malignant mesothelioma is a relatively rare malignancy arising in the body's serosal surfaces, with malignant pleural mesothelioma (MPM) being the most common type. It is characterized by local spread within the thorax, poor prognosis and resistance to treatment. The development of various immunotherapeutic options has provided a new way- and hope- in treating cancer patients. Chimeric antigen receptor (CAR) T cell therapy has been proven very successful in treating hematological cancers, like leukemias and lymphomas, and its use is now being tested in solid tumors. CARs that recognize and bind to a specific tumor-associated antigen on the tumor's cell surface, are engineered and transduced into T cells. Interaction of the CAR T cell with the tumor then results in T cell activation and subsequent tumor cell lysis. In this review, we provide a current update on our previous comprehensive study summarizing the CAR T cell preclinical studies and clinical trials in MM, and discuss the future perspectives of CAR T cell therapy in this disease.
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Affiliation(s)
- Astero Klampatsa
- Division of Cancer Therapeutics, The Institute of Cancer Research, London, UK
| | - Steven M Albelda
- Division of Pulmonary, Allergy and Critical Care, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
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Kisin ER, Yanamala N, Rodin D, Menas A, Farcas M, Russo M, Guppi S, Khaliullin TO, Iavicoli I, Harper M, Star A, Kagan VE, Shvedova AA. Enhanced morphological transformation of human lung epithelial cells by continuous exposure to cellulose nanocrystals. CHEMOSPHERE 2020; 250:126170. [PMID: 32114335 PMCID: PMC7750788 DOI: 10.1016/j.chemosphere.2020.126170] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/15/2019] [Revised: 01/30/2020] [Accepted: 02/09/2020] [Indexed: 05/06/2023]
Abstract
Cellulose nanocrystals (CNC), also known as nanowhiskers, have recently gained much attention due to their biodegradable nature, advantageous chemical and mechanical properties, economic value and renewability thus making them attractive for a wide range of applications. However, before these materials can be considered for potential uses, investigation of their toxicity is prudent. Although CNC exposures are associated with pulmonary inflammation and damage as well as oxidative stress responses and genotoxicity in vivo, studies evaluating cell transformation or tumorigenic potential of CNC's were not previously conducted. In this study, we aimed to assess the neoplastic-like transformation potential of two forms of CNC derived from wood (powder and gel) in human pulmonary epithelial cells (BEAS-2B) in comparison to fibrous tremolite (TF), known to induce lung cancer. Short-term exposure to CNC or TF induced intracellular ROS increase and DNA damage while long-term exposure resulted in neoplastic-like transformation demonstrated by increased cell proliferation, anchorage-independent growth, migration and invasion. The increased proliferative responses were also in-agreement with observed levels of pro-inflammatory cytokines. Based on the hierarchical clustering analysis (HCA) of the inflammatory cytokine responses, CNC powder was segregated from the control and CNC-gel samples. This suggests that CNC may have the ability to influence neoplastic-like transformation events in pulmonary epithelial cells and that such effects are dependent on the type/form of CNC. Further studies focusing on determining and understanding molecular mechanisms underlying potential CNC cell transformation events and their likelihood to induce tumorigenic effects in vivo are highly warranted.
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Affiliation(s)
- E R Kisin
- EAB, HELD, NIOSH, CDC, Morgantown, WV, USA
| | - N Yanamala
- EAB, HELD, NIOSH, CDC, Morgantown, WV, USA
| | - D Rodin
- Institute for Personalized and Translational Medicine, Ariel University, Ariel, Israel
| | - A Menas
- EAB, HELD, NIOSH, CDC, Morgantown, WV, USA
| | - M Farcas
- EAB, HELD, NIOSH, CDC, Morgantown, WV, USA
| | - M Russo
- EAB, HELD, NIOSH, CDC, Morgantown, WV, USA; Institute of Public Health, Section of Occupational Medicine, Catholic University of the Sacred Heart, Rome, Italy
| | - S Guppi
- EAB, HELD, NIOSH, CDC, Morgantown, WV, USA
| | - T O Khaliullin
- EAB, HELD, NIOSH, CDC, Morgantown, WV, USA; Department of Physiology & Pharmacology, WVU, Morgantown, WV, USA
| | - I Iavicoli
- Department of Public Health, University of Naples Federico II, Naples, Italy
| | - M Harper
- Zefon International, Ocala, FL, USA
| | - A Star
- Department of Chemistry, University of Pittsburgh, Pittsburgh, PA, USA
| | - V E Kagan
- Department of Environmental & Occupational Health, University of Pittsburgh, Pittsburgh, PA, USA; Center for Free Radical and Antioxidant Health, University of Pittsburgh, Pittsburgh, PA, USA; Laboratory of Navigational Redox Lipidomics, IM Sechenov Moscow State Medical University, Moscow, Russian Federation
| | - A A Shvedova
- EAB, HELD, NIOSH, CDC, Morgantown, WV, USA; Department of Physiology & Pharmacology, WVU, Morgantown, WV, USA.
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Marques de Sousa S, Pereira F, Duarte M, Marques M, Vázquez D, Marques C. Malignant Peritoneal Mesothelioma as a Rare Cause of Dyspeptic Complaints and Ascites: A Diagnostic Challenge. GE-PORTUGUESE JOURNAL OF GASTROENTEROLOGY 2020; 27:197-202. [PMID: 32509926 DOI: 10.1159/000503075] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/02/2019] [Revised: 08/31/2019] [Indexed: 12/12/2022]
Abstract
Introduction Malignant peritoneal mesothelioma (MPM) is a rare malignancy of the mesothelial cells in the peritoneum. The best-defined risk factor is asbestos exposure, but germline mutations in BAP1 also increase susceptibility to this tumor. The diagnosis of MPM is challenging since clinical manifestations are often nonspecific. Case Presentation We describe a case of MPM in a 53-year-old former construction worker with prior asbestos exposure. The clinical presentation was a 3-month history of dyspeptic complaints. As initial workup, abdominal ultrasound and upper gastrointestinal endoscopy were performed. Chronic gastritis due to Helicobacter pylori was detected, which was promptly treated but without symptom relief. Abdominal ultrasound showed small volume ascites with hyperechogenic foci, which was later confirmed on computed tomography scan showing the presence of peritoneal nodules in the greater omentum and mesentery. A thorough investigation was conducted based on the suspicion of peritoneal carcinomatosis. A non-peritoneal primary tumor was not found. Ascitic cytology and immunocytochemical studies were suggestive of mesothelioma. He underwent exploratory laparotomy and inoperable peritoneal disease was observed. Peritoneal biopsy confirmed epithelioid-type MPM. Systemic therapy was initiated with platinum plus pemetrexed with good response. The last follow-up was 38 months after the diagnosis. Discussion/Conclusion The diagnosis of MPM is challenging since it requires a high degree of suspicion. MPM has a poor prognosis. The standard of treatment recommended is cytoreductive surgery with hyperthermic intraperitoneal chemotherapy. For those who are inoperable, systemic therapy with pemetrexed-cisplatin combination is the alternative. Given the infrequency of disease, it is imperative to ensure patient participation in clinical trials with the purpose of treatment standardization.
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Affiliation(s)
- Susana Marques de Sousa
- Internal Medicine Department, Centro Hospitalar Póvoa de Varzim/Vila do Conde, Póvoa de Varzim, Portugal
| | - Filipa Pereira
- Oncology Department, Instituto Português de Oncologia do Porto, Porto, Portugal
| | - Maria Duarte
- Internal Medicine Department, Centro Hospitalar Póvoa de Varzim/Vila do Conde, Póvoa de Varzim, Portugal
| | - Marta Marques
- Internal Medicine Department, Centro Hospitalar Póvoa de Varzim/Vila do Conde, Póvoa de Varzim, Portugal
| | - Dolores Vázquez
- Internal Medicine Department, Centro Hospitalar Póvoa de Varzim/Vila do Conde, Póvoa de Varzim, Portugal
| | - Cristina Marques
- Internal Medicine Department, Centro Hospitalar Póvoa de Varzim/Vila do Conde, Póvoa de Varzim, Portugal
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HUANG Q, LAN YJ. Colorectal cancer and asbestos exposure-an overview. INDUSTRIAL HEALTH 2020; 58:200-211. [PMID: 31511437 PMCID: PMC7286717 DOI: 10.2486/indhealth.2018-0271] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/29/2018] [Accepted: 09/05/2019] [Indexed: 06/10/2023]
Abstract
The relationship between colorectal cancer and asbestos exposure has not been fully clarified. This study aimed to determine the associations between asbestos exposure and colorectal cancer. We performed a meta-analysis to quantitatively evaluate this association. A fixed effects model was used to summarize the relative risks across studies. Sources of heterogeneity were explored through subgroup analyses and meta-regression. We analyzed the dose-effect relationship using lung cancer standardized mortality ratio (SMR) and the risk of mesothelioma as a percent (%) as exposure surrogates. A total of 47 cohort studies were included. We identified 28 incidence cohort studies from 17 separate papers and extracted colorectal cancer standardized incidence ratio (SIR). Cancer mortality data were extracted from 19 separate cohorts among 13 papers. The overall colorectal cancer SMR for synthesis cohort was 1.07 (95% CI 1.02-1.12). Statistically significant excesses were observed in exposure to mixed asbestos (SMR/SIR=1.07), exposure to production (SMR/SIR=1.11), among asbestos cement workers (SMR/SIR=1.18) and asbestos textile workers (SMR/SIR=1.11). Additionally, we determined that the SMR for lung cancer increased with increased exposure to asbestos, as did the risk for colorectal cancer. This study confirms that colorectal cancer has a positive weak associations with asbestos exposure.
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Affiliation(s)
- Qian HUANG
- West China School of Public Health and West China Fourth
Hospital, Sichuan University, China
| | - Ya-jia LAN
- West China School of Public Health and West China Fourth
Hospital, Sichuan University, China
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