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International Journal of Molecular... Mar 2020Malignant mesothelioma is an infrequent tumor that initiates from the mesothelial cells lining of body cavities. The great majority of mesotheliomas originate in the... (Review)
Review
Malignant mesothelioma is an infrequent tumor that initiates from the mesothelial cells lining of body cavities. The great majority of mesotheliomas originate in the pleural cavity, while the remaining cases initiate in the peritoneal cavity, in the pericardial cavity or on the tunica vaginalis. Usually, mesotheliomas grow in a diffuse pattern and tend to enclose and compress the organs in the various body cavities. Mesothelioma incidence is increasing worldwide and still today, the prognosis is very poor, with a reported median survival of approximately one year from presentation. Thus, the development of alternative and more effective therapies is currently an urgent requirement. The aim of this review article was to describe recent findings about the anti-cancer activity of curcumin and some of its derivatives on mesotheliomas. The potential clinical implications of these findings are discussed.
Topics: Antineoplastic Agents; Curcumin; Humans; Mesothelioma, Malignant; Phytochemicals; Pleura; Pleural Neoplasms; Prognosis
PubMed: 32155978
DOI: 10.3390/ijms21051839 -
Advances in Respiratory Medicine 2020Malignant pleural mesothelioma (MPM) is a relatively rare, but highly lethal cancer of the pleural mesothelial cells. Its pathoge-nesis is integrally linked to asbestos... (Review)
Review
Malignant pleural mesothelioma (MPM) is a relatively rare, but highly lethal cancer of the pleural mesothelial cells. Its pathoge-nesis is integrally linked to asbestos exposure. In spite of recent developments providing a more detailed understanding of the pathogenesis, the outcomes continue to be poor. To date, trimodality therapy involving surgery coupled with chemotherapy and/or radiotherapy remains the standard of therapy. The development of resistance of the tumor cells to radiation and several che-motherapeutic agents poses even greater challenges in the management of this cancer. Ionizing radiation damages cancer cell DNA and aids in therapeutic response, but it also activates cell survival signaling pathways that helps the tumor cells to overcome radiation-induced cytotoxicity. A careful evaluation of the biology involved in mesothelioma with an emphasis on the workings of pro-survival signaling pathways might offer some guidance for treatment options. This review focuses on the existing treatment options for MPM, novel treatment approaches based on recent studies combining the use of inhibitors which target different pro-survival pathways, and radiotherapy to optimize treatment.
Topics: Antineoplastic Combined Chemotherapy Protocols; Asbestos; Clinical Trials as Topic; Humans; Mesothelioma, Malignant; Neoplasm Staging; Pleural Neoplasms; Radiotherapy, Adjuvant
PubMed: 32869268
DOI: 10.5603/ARM.a2020.0103 -
Cancer Research and Treatment Oct 2019Lung cancers presenting as subsolid nodule commonly have peripheral location, making the cancer-pleura relationship noteworthy. We aimed to evaluate the effect of...
PURPOSE
Lung cancers presenting as subsolid nodule commonly have peripheral location, making the cancer-pleura relationship noteworthy. We aimed to evaluate the effect of pleural attachment and/or indentation on visceral pleural invasion (VPI) and recurrence-free survival.
MATERIALS AND METHODS
Patients who underwent curative resection of lung cancer as subsolid nodules from April 2007 to January 2016 were retrospectively evaluated. They were divided into four groups according to their relationship with the pleura. Clinical, radiographical, and pathological findings were analyzed.
RESULTS
Among 404 patients with malignant subsolid nodule, 120 (29.7%) had neither pleural attachment nor indentation, 26 (6.4%) had attachment only, 117 (29.0%) had indentation only, and 141 (34.9%) had both. VPI was observed in nodules of 36 patients (8.9%), but absent in nonsolid nodules and in those without pleural attachment and/or indentation. Compared to subsolid nodules with concurrent pleural attachment and indentation, those with attachment only (odds ratio, 0.12; 95% confidence interval [CI], 0.02 to 0.98) and indentation only (odds ratio, 0.10; 95% CI, 0.03 to 0.31) revealed lower odds of VPI. On subgroup analysis, the size of the solid portion was associated with VPI among those with pleural attachment and indentation (p=0.021). Such high-risk features for VPI were associated with earlier lung cancer recurrence (adjusted hazard ratio, 3.31; 95% CI, 1.58 to 6.91).
CONCLUSION
Concurrent pleural attachment and indentation are risk factors for VPI, and the odds increase with larger solid portion in subsolid nodules. Considering the risk of recurrence, early surgical resection could be encouraged in these patients.
Topics: Aged; Female; Humans; Lung Neoplasms; Male; Middle Aged; Multiple Pulmonary Nodules; Neoplasm Invasiveness; Odds Ratio; Pleural Neoplasms; Pneumonectomy; Prognosis; Retrospective Studies; Treatment Outcome
PubMed: 30913858
DOI: 10.4143/crt.2019.057 -
Journal of Cancer Research and... 2018Malignant pleural mesothelioma (MPM) is a highly lethal and refractory to multimodal treatment tumor. Numb is considered as a tumor suppressor playing critical roles in...
AIM OF STUDY
Malignant pleural mesothelioma (MPM) is a highly lethal and refractory to multimodal treatment tumor. Numb is considered as a tumor suppressor playing critical roles in determining cell fate and has been shown to target the oncogenic transcription factor Gli1 for Itch-dependent ubiquitination, resulting in suppression of the oncogenic sonic hedgehog signaling in medulloblastoma. This study was designed to analysis the role of Numb and Gli1 in MPM.
MATERIALS AND METHODS
Tissues of 61 MPM patients and 22 normal pleura as control were investigated. Numb and Gli1 expression were evaluated by immunohistochemistry. The associations with clinical and pathological parameters of the two markers were statistically analyzed, and the correlation between them was also demonstrated.
RESULTS
The expression levels of Numb with nuclear Gli1 exhibited a significant inverse correlation (r = -0.361 P < 0.05). In addition, Numb has an inverse correlation with ki-67 labeling index (P < 0.05), and nuclear Gli1 was found in associated with the tumor International Mesothelioma Interest Group-stage (P < 0.05). The overall survival was influenced by the expression of Numb (P < 0.05) and histological subtype (P < 0.05), further regression analysis showed that only histological subtype has a prognostic influence on survival (P < 0.05).
CONCLUSION
The results provide new evidence of Numb and Gli1 on the clinical characteristics of MPM, which may be helpful in clinical diagnosis and targeted therapy. Further research with larger sample size is needed.
Topics: Aged; Cell Proliferation; Female; Gene Expression Regulation, Neoplastic; Humans; Lung Neoplasms; Male; Membrane Proteins; Mesothelioma; Mesothelioma, Malignant; Middle Aged; Molecular Targeted Therapy; Nerve Tissue Proteins; Pleural Neoplasms; Prognosis; Zinc Finger Protein GLI1
PubMed: 30197333
DOI: 10.4103/0973-1482.180614 -
Journal of Thoracic Oncology : Official... Nov 2018There is no approved second-line treatment for malignant pleural mesothelioma (MPM). On the basis of promising early results, pembrolizumab was used off-label in...
INTRODUCTION
There is no approved second-line treatment for malignant pleural mesothelioma (MPM). On the basis of promising early results, pembrolizumab was used off-label in Switzerland and Australia. We investigated outcomes in association with clinicopathological features and expression of programmed death ligand 1 (PD-L1).
METHODS
Registry data in Australia and Switzerland were pooled. Patient characteristics, including age, sex, histological subtype, and previous treatments were captured. Outcomes were assessed locally. PD-L1 expression was categorized as negative (<5%), intermediate (5%-49%), and high (≥50%).
RESULTS
A total of 93 patients (48 from Switzerland and 45 from Australia) were treated; 68 patients (73%) had epithelioid MPM, and 67 (72%) had an Eastern Cooperative Oncology Group performance status of 0 or 1. Pembrolizumab was the second-line treatment in 48 of 93 patients (52%). PD-L1 expression results were available for 66 patients (71%). Most (68%) were negative, 18% were intermediate, and 14% were high for PD-L1 expression. In the full cohort, the overall response rate (ORR) was 18%, the median progression-free survival (mPFS) was 3.1 months, and the median overall survival was 7.2 months. In patients with an Eastern Cooperative Oncology Group performance status of 0 or 1 and only one previous systemic treatment (n = 35), the ORR was 37%, the mPFS was 3.7 months, and the median overall survival was 10.2 months. The nonepitheloid histological subtype showed an improved ORR (24% versus 16% [p = 0.54) and mPFS (5.6 versus 2.8 months [p = 0.02]). Compared with intermediate and negative PD-L1 expression, high PD-L1 expression was associated with an improved ORR (44% versus 42% versus 11% [p = 0.01]) and mPFS (6.2 versus 3.9 versus 2.7 months [p = 0.04]). Toxicity was as expected.
CONCLUSION
These real-world data demonstrate similar response rates but inferior survival compared with those in early-phase trials. High PD-L1 expression and nonepitheloid histological subtype were associated with greater activity. Anti-PD-L1 immunotherapy is a reasonable second-line therapy in patients with MPM.
Topics: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal, Humanized; Antineoplastic Agents, Immunological; Female; Humans; Immunotherapy; Lung Neoplasms; Male; Mesothelioma; Mesothelioma, Malignant; Middle Aged; Pleural Neoplasms
PubMed: 30142389
DOI: 10.1016/j.jtho.2018.08.007 -
Cancer Reports (Hoboken, N.J.) Sep 2022Malignant mesothelioma is a rare neoplasm associated with asbestos exposure. Characterizing treatment patterns and outcomes of older patients with advanced malignant...
BACKGROUND
Malignant mesothelioma is a rare neoplasm associated with asbestos exposure. Characterizing treatment patterns and outcomes of older patients with advanced malignant pleural mesothelioma (MPM) is important to understand the unmet needs of this population.
AIM
To evaluate the demographic and clinical characteristics, treatment patterns, and outcomes among older patients diagnosed with advanced MPM in the United States between 2007 and 2013.
METHODS
This was a retrospective cohort study using Surveillance, Epidemiology, and End Results (SEER) data linked with Medicare claims. We included patients who were age 66 or older at the time of their primary MPM diagnosis between 2007 and 2013 and followed them through 2014. Treated patients who received first-line chemotherapy with pemetrexed and platinum within 90 days of diagnosis, second-line, or third-line therapy were identified for evaluation of outcomes.
RESULTS
There were 666 older patients with advanced MPM, of whom 82% were male, 87% White, 78% stage IV, and 70% had no mobility limitation indicators at diagnosis. There were 262 patients who received first-line chemotherapy for advanced MPM, most of whom (80%; n = 209) received pemetrexed-platinum. Of these 209 patients, 41% (n = 86) initiated second-line therapy, and 26% (n = 22) initiated third-line therapy. Median overall survival for the cohort of 209 patients was 7.2 months. Patients with epithelioid histology had better median overall survival (12.2 months) compared with other histologies (4.4-5.6 months). Within 90 days of diagnosis of advanced MPM, 78% of patients were hospitalized, 52% visited an emergency department, and 21% had hospice care. The 2-year cost of care was over $100 000 for all patients with advanced MPM treated with first-line pemetrexed-platinum.
CONCLUSIONS
Although first-line systemic anticancer treatment was generally consistent with guidelines (e.g., pemetrexed-platinum), poor patient outcomes highlight the need for effective treatment options for older patients with advanced MPM.
Topics: Aged; Female; Humans; Male; Medicare; Mesothelioma; Mesothelioma, Malignant; Pemetrexed; Platinum; Pleural Neoplasms; Retrospective Studies; United States
PubMed: 34698447
DOI: 10.1002/cnr2.1568 -
Journal of Toxicology and Environmental... 2016Despite the reduction of global asbestos consumption and production due to the ban or restriction of asbestos uses in more than 50 countries since the 1970s, malignant... (Review)
Review
Despite the reduction of global asbestos consumption and production due to the ban or restriction of asbestos uses in more than 50 countries since the 1970s, malignant mesothelioma remains a disease of concern. Asbestos is still used, imported, and exported in several countries, and the number of mesothelioma deaths may be expected to increase in the next decades in these countries. Asbestos exposure is the main risk factor for malignant pleural mesothelioma, but other types of exposures are linked to the occurrence of this type of cancer. Although recent treatments improve the quality of life of patients with mesothelioma, malignant pleural mesothelioma remains an aggressive disease. Recent treatments have not resulted in appreciable improvement in survival, and thus development of more efficient therapies is urgently needed. The development of novel therapeutic strategies is dependent on our level of knowledge of the physiopathological and molecular changes that mesothelial cells acquired during the neoplastic process. During the past 5 years, new findings have been published on the etiology, epidemiology, molecular changes, and innovative treatments of malignant pleural mesothelioma. This review aims to update the findings of recent investigations on etiology, epidemiology, and molecular changes with a focus on (1) attributable risk of asbestos exposure in men and women and (2) coexposure to other minerals and other elongated mineral particles or high aspect ratio nanoparticles. Recent data obtained on genomic and gene alterations, pathways deregulations, and predisposing factors are summarized.
Topics: Asbestos; Environmental Exposure; Humans; Lung Neoplasms; Mesothelioma; Mesothelioma, Malignant; Minerals; Nanoparticles; Occupational Exposure; Pleural Neoplasms
PubMed: 27705546
DOI: 10.1080/10937404.2016.1193361 -
Journal of Thoracic Oncology : Official... Aug 2022
Topics: Humans; Lung Neoplasms; Mesothelioma; Mesothelioma, Malignant; Pleural Neoplasms
PubMed: 35931424
DOI: 10.1016/j.jtho.2022.04.014 -
BMC Pulmonary Medicine Apr 2018Malignant pleural mesothelioma (MPM) is marked by its difficult diagnosis and poor prognosis. Medical thoracoscopy (MT) is an effective and safe procedure for the...
BACKGROUND
Malignant pleural mesothelioma (MPM) is marked by its difficult diagnosis and poor prognosis. Medical thoracoscopy (MT) is an effective and safe procedure for the diagnosis of exudative pleural effusions and many factors associated with poor prognosis of MPM. We conducted this study to investigate the value of MT for diagnosing of MPM and to identify prognostic factors for MPM patients.
METHODS
From July 2005 through June 2014, a total of 833 patients with undiagnosed pleural effusions underwent MT and pleural biopsies were taken. Clinical data of all patients with MPM were retrospectively analyzed, and those with complete follow-up data were analyzed for prognostic factors.
RESULTS
Eventually, MPM was the final diagnosis in 40 patients. Diagnostic efficiency of MT for MPM was 87.5%, since diagnosis of MPM failed to be established in 5 patients during the initial MT. Median survival was 17.1 mo (95% confidence interval: 13.6-20.7 mo). MT findings of pleural adhesion and plaques were adverse prognostic factors for MPM. In addition, old age, male gender, smoking history, histological type, poor staging, no treatment, low total protein level in pleural fluid, and computed tomographic findings such as pulmonary consolidation or infiltration, mediastinal lymphopathy, pulmonary mass or nodules, and pleural nodularity were also poor prognostic factors for MPM.
CONCLUSIONS
MT is safe with a high positive rate in the diagnosis of MPM, and pleural adhesion and plaques seen under MT may be the adverse prognostic factors for MPM. Multiple clinical characteristics can affect the survival of MPM patients.
Topics: Adult; Aged; Biopsy; China; Disease Progression; Female; Humans; Lung Neoplasms; Male; Mesothelioma; Mesothelioma, Malignant; Middle Aged; Neoplasm Staging; Outcome Assessment, Health Care; Pleura; Pleural Effusion, Malignant; Pleural Neoplasms; Predictive Value of Tests; Prognosis; Retrospective Studies; Risk Factors; Thoracoscopy; Treatment Outcome
PubMed: 29615010
DOI: 10.1186/s12890-018-0619-3 -
Zhongguo Fei Ai Za Zhi = Chinese... May 2024Malignant pleural mesothelioma (MPM) is a rare cancer with high malignancy and aggressiveness on the pleural, caused by the following risk factors including asbestos... (Review)
Review
Malignant pleural mesothelioma (MPM) is a rare cancer with high malignancy and aggressiveness on the pleural, caused by the following risk factors including asbestos inhalation, genetic factors, and genetic mutation. The present chemotherapy, antiangiogenic therapy, and immunotherapy methods are ineffective and the survival time of patients is very short. There is an urgent need to find potential therapeutic targets for MPM. At present, it has been found the following types of targets: gene mutation targets such as BRCA associated protein 1 (BAP1) and cyclin-dependent kinase 2A (CDKN2A); epigenetic targets such as lysine (K)-specific demethylase 4A (KDM4A) and lysine-specific demethylase 1 (LSD1), and signal protein targets such as glucose-regulated protein 78 (GRP78) and signal transducer and activator of transcription 3 (STAT3). So far, available clinical trials include phase II clinical trials of histone methyltransferase inhibitor Tazemetostat, poly (ADP-ribose) polymerase (PARP) inhibitor Rucaparib and cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitor Abemaciclib, as well as phase I clinical trials of mesothelin-targeting chimeric antigen receptor T-cell immunotherapy (CAR-T) cell injection in the thoracic cavity and TEA domain family member (TEAD) inhibitor VT3989 and IK-930, and the results of these trials have showed certain clinical efficacy. .
Topics: Humans; Mesothelioma, Malignant; Mesothelioma; Lung Neoplasms; Molecular Targeted Therapy; Pleural Neoplasms; Animals; Endoplasmic Reticulum Chaperone BiP
PubMed: 38880927
DOI: 10.3779/j.issn.1009-3419.2024.102.18