Biomarkers for malignant pleural mesothelioma: a meta-analysis

Abstract Malignant pleural mesothelioma (MPM) is a rare but aggressive cancer, and early detection is associated with better survival. Mesothelin, fibulin-3 and osteopontin have been suggested as screening biomarkers. The study conducted a meta-analysis of the mean differences of mesothelin, osteopontin and fibulin-3 in blood and pleural samples. PubMed searches were conducted for studies that measured levels of mesothelin, osteopontin and fibulin-3 in participants with MPM compared with malignancy, benign lung disease or healthy participants. Thirty-two studies with mesothelin levels, 12 studies with osteopontin levels and 9 studies with fibulin-3 levels were included in the meta-analysis. Statistically significant mean differences were seen between MPM patients and all other comparison groups for mesothelin blood and pleural levels. Statistically significant differences in blood osteopontin levels were seen between participants with benign lung disease and healthy participants compared with participants with MPM, but not when comparing participants with cancer with MPM participants. There were not enough studies that reported osteopontin levels in pleural fluid to complete a meta-analysis. Statistically significant differences were seen in both blood and pleural levels of fibulin-3 in MPM patients compared with all other groups. On the basis of these results, mesothelin and fibulin-3 levels appear to be significantly lower in all control groups compared with those with MPM, making them good candidates for screening biomarkers. Osteopontin may be a useful biomarker for screening healthy individuals or those with benign lung disease but would not be useful for screening patients with malignancies.

Download Full-text

Relationship between total plasma homocysteine and the risk of aneurysms – a meta-analysis

VASA ◽

10.1024/0301-1526/a000891 ◽

2020 ◽

pp. 1-6

Author(s):

Hanji Zhang ◽

Dexin Yin ◽

Yue Zhao ◽

Yezhou Li ◽

Dejiang Yao ◽

...

Keyword(s):

Large Scale ◽

Meta Analysis ◽

Single Species ◽

Total Plasma ◽

Control Groups ◽

Randomized Controlled ◽

Randomized Controlled Studies ◽

The Difference ◽

The Relationship ◽

Healthy Participants

Summary: Our meta-analysis focused on the relationship between homocysteine (Hcy) level and the incidence of aneurysms and looked at the relationship between smoking, hypertension and aneurysms. A systematic literature search of Pubmed, Web of Science, and Embase databases (up to March 31, 2020) resulted in the identification of 19 studies, including 2,629 aneurysm patients and 6,497 healthy participants. Combined analysis of the included studies showed that number of smoking, hypertension and hyperhomocysteinemia (HHcy) in aneurysm patients was higher than that in the control groups, and the total plasma Hcy level in aneurysm patients was also higher. These findings suggest that smoking, hypertension and HHcy may be risk factors for the development and progression of aneurysms. Although the heterogeneity of meta-analysis was significant, it was found that the heterogeneity might come from the difference between race and disease species through subgroup analysis. Large-scale randomized controlled studies of single species and single disease species are needed in the future to supplement the accuracy of the results.

Download Full-text

Hitting the Bull’s-Eye: Mesothelin’s Role as a Biomarker and Therapeutic Target for Malignant Pleural Mesothelioma

Cancers ◽

10.3390/cancers13163932 ◽

2021 ◽

Vol 13 (16) ◽

pp. 3932

Author(s):

Dannel Yeo ◽

Laura Castelletti ◽

Nico van Zandwijk ◽

John E. J. Rasko

Keyword(s):

Malignant Pleural Mesothelioma ◽

Treatment Options ◽

Survival Rates ◽

Treatment Strategies ◽

Pleural Mesothelioma ◽

Normal Tissues ◽

Drug Conjugates ◽

Aggressive Cancer ◽

Immunotherapy Target ◽

Bull's Eye

Malignant pleural mesothelioma (MPM) is an aggressive cancer with limited treatment options and poor prognosis. MPM originates from the mesothelial lining of the pleura. Mesothelin (MSLN) is a glycoprotein expressed at low levels in normal tissues and at high levels in MPM. Many other solid cancers overexpress MSLN, and this is associated with worse survival rates. However, this association has not been found in MPM, and the exact biological role of MSLN in MPM requires further exploration. Here, we discuss the current research on the diagnostic and prognostic value of MSLN in MPM patients. Furthermore, MSLN has become an attractive immunotherapy target in MPM, where better treatment strategies are urgently needed. Several MSLN-targeted monoclonal antibodies, antibody–drug conjugates, immunotoxins, cancer vaccines, and cellular therapies have been tested in the clinical setting. The biological rationale underpinning MSLN-targeted immunotherapies and their potential to improve MPM patient outcomes are reviewed.

Download Full-text

Identification of Redox-Sensitive Transcription Factors as Markers of Malignant Pleural Mesothelioma

Cancers ◽

10.3390/cancers13051138 ◽

2021 ◽

Vol 13 (5) ◽

pp. 1138

Author(s):

Martina Schiavello ◽

Elena Gazzano ◽

Loredana Bergandi ◽

Francesca Silvagno ◽

Roberta Libener ◽

...

Keyword(s):

Oxidative Stress ◽

Transcription Factors ◽

Malignant Pleural Mesothelioma ◽

Antioxidant Defense ◽

Asbestos Exposure ◽

Predictive Biomarkers ◽

Antioxidant Systems ◽

Pleural Mesothelioma ◽

Related Factor ◽

Aggressive Cancer

Although asbestos has been banned in most countries around the world, malignant pleural mesothelioma (MPM) is a current problem. MPM is an aggressive tumor with a poor prognosis, so it is crucial to identify new markers in the preventive field. Asbestos exposure induces oxidative stress and its carcinogenesis has been linked to a strong oxidative damage, event counteracted by antioxidant systems at the pulmonary level. The present study has been focused on some redox-sensitive transcription factors that regulate cellular antioxidant defense and are overexpressed in many tumors, such as Nrf2 (Nuclear factor erythroid 2-related factor 2), Ref-1 (Redox effector factor 1), and FOXM1 (Forkhead box protein M1). The research was performed in human mesothelial and MPM cells. Our results have clearly demonstrated an overexpression of Nrf2, Ref-1, and FOXM1 in mesothelioma towards mesothelium, and a consequent activation of downstream genes controlled by these factors, which in turn regulates antioxidant defense. This event is mediated by oxidative free radicals produced when mesothelial cells are exposed to asbestos fibers. We observed an increased expression of Nrf2, Ref-1, and FOXM1 towards untreated cells, confirming asbestos as the mediator of oxidative stress evoked at the mesothelium level. These factors can therefore be considered predictive biomarkers of MPM and potential pharmacological targets in the treatment of this aggressive cancer.

Download Full-text

Effectiveness of orthodontic temporary anchorage devices in canine retraction and anchorage preservation during the two-step technique: a systematic review and meta-analysis

BMC Oral Health ◽

10.1186/s12903-020-01271-8 ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Haonan Tian ◽

Congman Xie ◽

Min Lin ◽

Hongmei Yang ◽

Aishu Ren

Keyword(s):

Systematic Review ◽

Meta Analysis ◽

Risk Of Bias ◽

Controlled Trials ◽

Cochrane Central Register ◽

Canine Retraction ◽

Temporary Anchorage Devices ◽

The Mean ◽

Mean Differences ◽

Implant Anchorage

Abstract Background Temporary anchorage devices have been used for decades in orthodontic practice for many applications. The aim of this systematic review was to assess the effectiveness of orthodontic temporary anchorage devices in canine retraction during the two-step technique. Methods A search was systematically performed for articles published prior to June 30, 2019 in five electronic databases (PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, Scopus). The risk of bias was assessed using the Cochrane risk of bias tool for randomized controlled trials (RCTs) and the risk of bias in nonrandomized studies of interventions (ROBINS-I) tool for controlled clinical trials (CCTs). The Grading of Recommendation, Assessment, Development and Evaluation (GRADE) approach was used for the quality assessment. Data concerning the mean difference in mesial molar movement and extent of canine retraction were extracted for statistical analysis. The mean differences and 95% confidence intervals were analyzed for continuous data. A meta-analysis with a random-effects model for comparable outcomes was carried out. Results Three RCTs and five CCTs were finally included. Meta-analysis showed a significant increase not only in anchorage preservation in the implant anchorage group in both the maxilla (1.56 mm, 95% CI: 1.14 to 1.98, P < 0.00001) and the mandible (1.62 mm, 95% CI: 1.24 to 2.01, P < 0.00001) but also in canine retraction in the implant anchorage group in both the maxilla (0.43 mm, 95% CI: 0.16 to 0.69, P = 0.001) and the mandible (0.26 mm, 95% CI: 0.02 to 0.49, P = 0.03). Conclusions There is very low-quality evidence showing that implant anchorage is more efficient than conventional anchorage during canine retraction. Additional high-quality studies are needed.

Download Full-text

Meta-Analysis: Randomized Trials of Lactobacillus plantarum on Immune Regulation Over the Last Decades

Frontiers in Immunology ◽

10.3389/fimmu.2021.643420 ◽

2021 ◽

Vol 12 ◽

Author(s):

Wei Zhao ◽

Chuantao Peng ◽

Hafiz Arbab Sakandar ◽

Lai-Yu Kwok ◽

Wenyi Zhang

Keyword(s):

Meta Analysis ◽

Controlled Trials ◽

Cochrane Central Register ◽

Central Register ◽

Tnf Α ◽

Ifn Γ ◽

The Mean ◽

Regulatory Effects ◽

Mean Differences ◽

Necrosis Factor

Lactobacillus (L.) plantarum strains, belong to lactic acid bacteria group, are considered indispensable probiotics. Here, we performed meta-analysis to evaluate the regulatory effects of L. plantarum on the immunity during clinical trials. This meta-analysis was conducted by searching across four most common literature databases, namely, Cochrane Central Register of Controlled Trials, Web of Science, Embase, and PubMed. Clinical trial articles that met the inclusion and exclusion criteria were analyzed by Review Manager (version 5.3). p-value < 0.05 of the total effect was considered statistically significant. Finally, total of 677 references were retrieved, among which six references and 18 randomized controlled trials were included in the meta-analysis. The mean differences observed at 95% confidence interval: interleukin (IL)-4, −0.48 pg/mL (−0.79 to −0.17; p < 0.05); IL-10, 9.88 pg/mL (6.52 to 13.2; p < 0.05); tumor necrosis factor (TNF)-α, −2.34 pg/mL (−3.5 to −1.19; p < 0.05); interferon (IFN)-γ, −0.99 pg/mL (−1.56 to −0.41; p < 0.05). Therefore, meta-analysis results suggested that L. plantarum could promote host immunity by regulating pro-inflammatory and anti-inflammatory cytokines.

Download Full-text

Intrapleural cisplatin and mitomycin for malignant mesothelioma following pleurectomy: pharmacokinetic studies.

Journal of Clinical Oncology ◽

10.1200/jco.1992.10.6.1001 ◽

1992 ◽

Vol 10 (6) ◽

pp. 1001-1006 ◽

Cited By ~ 76

Author(s):

V W Rusch ◽

D Niedzwiecki ◽

Y Tao ◽

C Menendez-Botet ◽

A Dnistrian ◽

...

Keyword(s):

Pleural Fluid ◽

Malignant Pleural Mesothelioma ◽

Plasma Levels ◽

Peak Plasma ◽

Systemic Absorption ◽

Pharmacokinetic Studies ◽

Logarithmic Scale ◽

Pleural Mesothelioma ◽

Intrapleural Chemotherapy ◽

The Mean

PURPOSE Intrapleural cisplatin-based chemotherapy has been used in the treatment of patients with malignant pleural mesothelioma and malignant pleural effusions, but the pharmacokinetics of this form of chemotherapy have not been previously evaluated. We performed pharmacokinetic studies on 12 patients who received both intrapleural cisplatin and mitomycin immediately following pleurectomy/decortication for malignant pleural mesothelioma. PATIENTS AND METHODS Simultaneous pleural fluid and plasma samples were collected at 15 and 30 minutes, and at 1, 2, 3, 4, and 24 hours after administration of the intrapleural chemotherapy (cisplatin 100 mg/m2 and mitomycin 8 mg/m2), and after cisplatin (total and free) and mitomycin levels were measured. The mean peak levels, the areas under the concentration-time curve (AUC) and the drug half-lives (t1/2s) in plasma and pleural fluid were compared using the paired t test. Differences were considered significant if P less than or equal to .05. RESULTS Systemic absorption was rapid, with peak plasma levels being reached within 1 hour of administration of the intrapleural chemotherapy. Peak plasma levels measured after intrapleural chemotherapy approximated those reportedly attained during systemic administration of these drugs at similar doses. However, the mean peak cisplatin and mitomycin levels, and their mean AUCs, were significantly higher in the pleural fluid than in the plasma. There was a three- to fivefold advantage (on a logarithmic scale) for pleural to plasma AUCs for both cisplatin and mitomycin. The mean t1/2s for cisplatin and mitomycin were significantly longer in the plasma than in the pleural fluid. CONCLUSIONS The pharmacokinetics of intrapleural cisplatin-based chemotherapy are analogous to those of intraperitoneal chemotherapy. Our findings show that intrapleural cisplatin-based chemotherapy has a distinct local pharmacologic advantage, but also produces significant and sustained drug plasma levels.

Download Full-text

Patient-derived malignant pleural mesothelioma cell cultures: a tool to advance biomarker-driven treatments

Thorax ◽

10.1136/thoraxjnl-2020-215027 ◽

2020 ◽

Vol 75 (11) ◽

pp. 1004-1008 ◽

Cited By ~ 1

Author(s):

Nikolaos I Kanellakis ◽

Rachelle Asciak ◽

Megat Abd Hamid ◽

Xuan Yao ◽

Mark McCole ◽

...

Keyword(s):

Cell Cultures ◽

Malignant Pleural Mesothelioma ◽

Poor Prognosis ◽

Ex Vivo ◽

Cytotoxic T Cells ◽

Pleural Mesothelioma ◽

Ex Vivo Model ◽

High Throughput Drug Screening ◽

Aggressive Cancer ◽

Malignant Pleural Mesothelioma Cell

Malignant pleural mesothelioma (MPM) is an aggressive cancer, associated with poor prognosis. We assessed the feasibility of patient-derived cell cultures to serve as an ex vivo model of MPM. Patient-derived MPM cell cultures (n=16) exhibited stemness features and reflected intratumour and interpatient heterogeneity. A subset of the cells were subjected to high-throughput drug screening and coculture assays with cancer-specific cytotoxic T cells and showed diverse responses. Some of the biphasic MPM cells were capable of processing and presenting the neoantigen SSX-2 endogenously. In conclusion, patient-derived MPM cell cultures are a promising and faithful ex vivo model of MPM.

Download Full-text

Comparing iStent versus CyPass with or without phacoemulsification in patients with glaucoma: a meta-analysis

Therapeutic Advances in Chronic Disease ◽

10.1177/2040622318820850 ◽

2019 ◽

Vol 10 ◽

pp. 204062231882085 ◽

Cited By ~ 1

Author(s):

Ali Mahdavi Fard ◽

Sangita P. Patel ◽

Leili Pourafkari ◽

Nader D. Nader

Keyword(s):

Intraocular Pressure ◽

Meta Analysis ◽

Cochrane Review ◽

Cataract Extraction ◽

Lowering Effect ◽

The Mean ◽

Mean Differences ◽

Review Manager

Bacground: The aim of this study was to conduct a meta-analysis to compare the overall intraocular pressure (IOP)-lowering effect of iStent or CyPass as isolated procedures or in combination with cataract extraction. Materials and methods: Cochrane review manager 5.3 software (RevMan® 5.3) was used for a meta-analysis of IOPs and the number of antiglaucoma medications in six groups according to the type and number of stents and whether the procedure was isolated or in combination with cataract extraction. Main results: A total of 33 out of 446 publications retrieved have been enrolled. The mean changes in IOP in the groups with one iStent and more than two iStents with concurrent cataract extraction were −3.78 ± 0.53 mmHg and −3.89 ± 0.73 mmHg, respectively. The mean differences in IOP in the groups with one iStent and more than two iStents without concurrent cataract extraction were −3.96 ± 0.25 mmHg and −7.48 ± 0.55 mmHg, respectively. The mean changes in IOP in the groups with CyPass implantation with and without concurrent cataract extraction were −4.97 ± 1.38 mmHg and −8.96 ± 0.16 mmHg, respectively. Conclusions: Both iStent and CyPass either in combination with cataract extraction or as isolated procedures effectively decrease IOP. This effect is greatest with isolated implantation of CyPass followed by multiple iStents and then single iStent implantation and lasts up to 2 years.

Download Full-text