BioMed Research International

Our medical research library holds 21 studies published in BioMed Research International (2013–2023). Each entry links to the study's record on PubMed and, where there is one, to the publisher's page and a free full text. 21 have an abstract, the authors' own summary as PubMed records it: open "Abstract" to read it.

About the journal

• Publisher: Wiley
• Published: 2012 to the present, United States
• Language: English
• ISSN: 2314-6141 (electronic), 2314-6133 (print)
• Continues: Journal of Biomedicine and Biotechnology
• Its record in the NLM Catalog

2020s

• Retracted. Applications of Neural Network-Based Plan-Cancer Method for Primary Diagnosis of Mesothelioma Cancer. D. Kapila, S. Panwar, M.K.M.M. Raja, et al. 2023;2023:3164166. PubMed · Publisher · Free full text

  Abstract

  "Malignant mesothelioma (MM)" is an uncommon although fatal form of cancer. The proper MM diagnosis is crucial for efficient therapy and has significant medicolegal implications. Asbestos is a carcinogenic material that poses a health risk to humans. One of the most severe types of cancer induced by asbestos is "malignant mesothelioma." Prolonged shortness of breath and continuous pain are the most typical symptoms of the condition. The importance of early treatment and diagnosis cannot be overstated. The combination "epithelial/mesenchymal appearance of MM," however, makes a definite diagnosis difficult. This study is aimed at developing a deep learning system for medical diagnosis MM automatically. Otherwise, the sickness might cause patients to succumb to death in a short amount of time. Various forms of artificial intelligence algorithms for successful "Malignant Mesothelioma illness" identification are explored in this research. In relation to the concept of traditional machine learning, the techniques support "Vector Machine, Neural Network, and Decision Tree" are chosen. SPSS has been used to analyze the result regarding the applications of Neural Network helps to diagnose MM.

  Copyright © 2023 Dhiraj Kapila et al.

• High Expression of SMO and GLI1 Genes with Poor Prognosis in Malignant Mesothelioma. G.Y. Ma, S. Shi, Y.Z. Sang, et al. 2023;2023:6575194. PubMed · Publisher · Free full text

  Abstract

  Background: To investigate the value of SMO and GLI1 genes in the hedgehog pathway in malignant mesothelioma specimens. Further study on the expression and prognosis of SMO and GLI1 in malignant mesothelioma tissues and the relationship between the two and the molecular mechanisms of mesothelioma immunity and to further investigate the prognostic value of mesothelioma expression.

  Materials And Methods: Immunohistochemistry and RT-qPCR were applied to detect the expression of SMO and GLI1 proteins and mRNA in biopsy specimens and plasma cavity effusion specimens from malignant mesothelioma (n = 130) and benign mesothelial tissues (n = 50) and to analyze the clinicopathological significance and survival risk factors of SMO and GLI1 protein expression in mesothelioma. The mechanisms of mesothelioma cell expression and immune cell infiltration were investigated using bioinformatics methods.

  Results: SMO and GLI1 in mesothelioma tissues detected high concordance between the diagnostic results of mesothelioma biopsy specimens and plasma cavity effusion specimens. The expression levels of SMO and GLI1 protein and mRNA in mesothelioma tissues were higher than those in benign mesothelioma tissues. The expression levels of SMO and GLI1 protein were correlated with the age, site, and asbestos exposure history of patients with mesothelioma. The expression levels of SMO and GLI1 protein were correlated with the expressions of ki67 and p53 (P < 0.05). SMO and GLI1 gene expression levels were negatively correlated with good prognosis in mesothelioma patients (P < 0.05). Cox proportional risk model indicated that protein expressions of invasion, lymph node metastasis, distant metastasis, staging, and genes were independent prognostic factors of mesothelioma. The GEPIA database showed the overall survival rate and the disease-free survival rate of mesothelioma patients in the high SMO and GLI1 expression groups; the UALCAN database analysis showed lower SMO expression levels in mesothelioma patients with more pronounced TP53 mutations (P = 0.001); GLI1 gene expression levels were strongly correlated with lymph node metastasis in mesothelioma patients (P = 0.009). Timer database analysis showed that the mechanism of immune cell infiltration was closely related to SMO and GLI1 expression. The degree of immune cell infiltration was strongly correlated with the prognosis of mesothelioma patients (P < 0.05).

  Conclusion: The expression levels of both SMO and GLI1 proteins were higher than those of normal mesothelial tissues, and the mRNA expression levels also changed in the same direction. SMO and GLI1 gene expressions in mesothelioma were negatively correlated with age, site of occurrence, and history of asbestos exposure. Positive expression of SMO and GLI1 was negatively correlated with patient survival. The Cox proportional risk model showed that gender, history of asbestos exposure, site of occurrence, SMO, and GLI1 were independent prognostic factors for mesothelioma. The mechanism of immune cell infiltration in mesothelioma is closely related to the gene expression of both and the survival prognosis of mesothelioma patients.

  Copyright © 2023 Guan-Ying Ma et al.

• Retracted. Classification and Detection of Mesothelioma Cancer Using Feature Selection-Enabled Machine Learning Technique. M. Shobana, V.R. Balasraswathi, R. Radhika, et al. 2022;2022:9900668. PubMed · Publisher · Free full text

  Abstract

  Cancer of the mesothelium, sometimes referred to as malignant mesothelioma (MM), is an extremely uncommon form of the illness that almost always results in death. Chemotherapy, surgery, radiation therapy, and immunotherapy are all potential treatments for multiple myeloma; however, the majority of patients are identified with the disease at an advanced stage, at which time it is resistant to these therapies. After obtaining a diagnosis of advanced multiple myeloma, the average length of time that a person lives is one year after hearing this news. There is a substantial link between asbestos exposure and mesothelioma (MM). Using an approach that enables feature selection and machine learning, this article proposes a classification and detection method for mesothelioma cancer. The CFS correlation-based feature selection approach is first used in the feature selection process. It acts as a filter, selecting just the traits that are relevant to the categorization. The accuracy of the categorization model is improved as a direct consequence of this. After that, classification is carried out with the help of naive Bayes, fuzzy SVM, and the ID3 algorithm. Various metrics have been utilized during the process of measuring the effectiveness of machine learning strategies. It has been discovered that the choice of features has a substantial influence on the accuracy of the categorization.

  Copyright © 2022 M. Shobana et al.

• Prognostic Bone Metastasis-Associated Immune-Related Genes Regulated by Transcription Factors in Mesothelioma. Z. Hao, S. Wang, Z. Zheng, et al. 2022;2022:9940566. PubMed · Publisher · Free full text

  Abstract

  Mesothelioma (MESO) is a mesothelial originate neoplasm with high morbidity and mortality. Despite advancement in technology, early diagnosis still lacks effectivity and is full of pitfalls. Approaches of cancer diagnosis and therapy utilizing immune biomarkers and transcription factors (TFs) have attracted more and more attention. But the molecular mechanism of these features in MESO bone metastasis has not been thoroughly studied. Utilizing high-throughput genome sequencing data and lists of specific gene subsets, we performed several data mining algorithm. Single-sample Gene Set Enrichment Analysis (ssGSEA) was applied to identify downstream immune cells. Potential pathways involved in MESO bone metastasis were identified using Gene Oncology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, Gene Set Variation Analysis (GSVA), Gene Set Enrichment Analysis (GSEA), and Cox regression analysis. Ultimately, a model to help early diagnosis and to predict prognosis was constructed based on differentially expressed immune-related genes between bone metastatic and nonmetastatic MESO groups. In conclusion, immune-related gene SDC2, regulated by TFs TCF7L1 and POLR3D, had an important role on immune cell function and infiltration, providing novel biomarkers and therapeutic targets for metastatic MESO.

  Copyright © 2022 Zhiquan Hao et al.

• COL1A1 Is a Potential Prognostic Biomarker and Correlated with Immune Infiltration in Mesothelioma. C. Zhang, S. Liu, X. Wang, et al. 2021;2021:5320941. PubMed · Publisher · Free full text

  Abstract

  Objective: Mesothelioma (MESO) is a rare tumor derived from mesothelium cells. The aim of this study was to explore key candidate genes and potential molecular mechanisms for mesothelioma through bioinformatics analysis.

  Methods: The MESO expression profiles came from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. The differences in the infiltration levels of immune cells between MESO and normal tissues were assessed using CIBERSORT. Differentially expressed genes (DEGs) were identified by comprehensive analysis of multiple datasets. A protein-protein interaction (PPI) network was constructed, and a hub gene COL1A1 was selected for MESO. The expression and mutation of COL1A1 in MESO were analyzed in the cBioPortal database. The correlation between COL1A1 expression and immune cell infiltration was evaluated using the TIMER database. Gene Set Enrichment Analysis (GSEA) of COL1A1 was then performed. Finally, Kaplan-Meier survival analysis was presented to predict the survival times between high and low COL1A1 expression groups for MESO patients.

  Results: There were distinct differences in the infiltration levels of immune cells between MESO and normal tissues. A total of 118 DEGs were identified by comprehensively analyzing three expression profile datasets. COL1A1, a hub gene, was identified to be highly expressed in MESO compared to normal tissues. COL1A1 genetic mutation occurred in 9% of MESO samples, and amplification was the most common type of mutation. COL1A1 expression was significantly correlated to the infiltration levels of CD4+ T cells, macrophages, and neutrophils. GSEA results indicated that COL1A1 could be involved in key biological processes and pathways like extracellular matrix and PI3K-Akt pathway. Patients with high COL1A1 expression usually experienced shorten overall survival time than those with its low expression.

  Conclusion: Our findings revealed that COL1A1 could become a potential prognostic biomarker for MESO, which was significantly related to immune cell infiltration.

  Copyright © 2021 Cangang Zhang et al.

• Effects of Occupational Hazards on Job Stress and Mental Health of Factory Workers and Miners: A Propensity Score Analysis. Y. Lu, Z. Zhang, H. Yan, et al. 2020;2020:1754897. PubMed · Publisher · Free full text

  Abstract

  This study is to evaluate the effects of different occupational hazards on job stress and mental health of factory workers and miners. A total of 6120 workers from factories and mining enterprises in seven districts and one district of Urumqi were determined using the stratified cluster random sampling method. The Effort-Reward Imbalance (ERI) questionnaire and the Symptom Checklist-90 (SCL-90) were used to evaluate the effects of occupational hazard factors on job stress and mental health of workers. The propensity score analysis was used to control the confounding factors. The occupational hazards affecting job stress of workers were asbestos dust (OR = 1.3, 95% CI: 1.09-1.55), benzene (OR = 1.25, 95% CI: 1.10-1.41), and noise (OR = 1.39, 95% CI: 1.22-1.59). The occupational hazards affecting the mental health of workers were coal dust (OR = 1.19, 95% CI: 1.02-1.38), asbestos dust (OR = 1.58, 95% CI: 1.32-1.92), benzene (OR = 1.28, 95% CI: 1.13-1.47), and noise (OR = 1.23, 95% CI: 1.07-1.42). Different occupational hazards have certain influence on job stress and mental health of factory workers and miners. The enhancements in occupational hazard and risk assessment, occupational health examination, and occupational protection should be taken to relieve job stress and enhance the mental health of factory workers and miners.

  Copyright © 2020 Yaoqin Lu et al.

• The Status of Occupational Burnout and Its Influence on the Psychological Health of Factory Workers and Miners in Wulumuqi, China. Y. Lu, Z. Zhang, S. Gao, et al. 2020;2020:6890186. PubMed · Publisher · Free full text

  Abstract

  The purpose of this study was to investigate the status of occupational burnout and its influence on the psychological health of factory workers and miners, in order to provide theoretical basis and reference for alleviating occupational burnout and promoting psychological health. The cross-sectional study investigated 6130 factory workers and miners with online questionnaire; the Chinese Maslach Burnout Inventory (CMBI) and Symptom Check List-90 (SCL-90) were used. In total, 6120 valid questionnaires were collected; effectiveness was 99.8%. The percentage of the factory workers and miners suffering from occupational burnout was 85.98% and psychological health problems was 38.27%. A statistically significant difference was observed in relation to the prevalence of occupational burnout among factory workers and miners of different sex, education level, labor contracts, work schedule, monthly incomes, weight, hypertension, age, working years, working hours per day, working hours per week, coal dust, silica dust, asbestos dust, benzene, lead, and noise. The detection rate of psychological health was higher for males than females. The detection rate of psychological health was higher for working days per week less than 5 days than more than 5 days. The detection rate of psychological health with high school education, senior professional title, night shift, divorced, monthly income less than 3000 yuan, weight more than 75 kg, age more than 45 years, and working years between 25 and 30 years was higher than that of the other groups. The results showed that sex, education level, professional title, work schedule, monthly income, hypertension, age, working years, asbestos dust, benzene, and occupational burnout affected psychological health among factory workers and miners. Factory workers and miners had high levels of occupational burnout, and occupational burnout was a risk factor that can lead to psychological health.

  Copyright © 2020 Yaoqin Lu et al.

2010s

• Dosimetric Comparison of Lung-Sparing Radiation Therapy between Volumetric Arc Therapy and Helical Tomotherapy for Unresectable Malignant Pleural Mesothelioma. B. Pehlivan, K. Sengul, A. Yesil, et al. 2019;2019:4568958. PubMed · Publisher · Free full text

  Abstract

  Objective: To compare volumetric arc therapy (VMAT) and helical tomotherapy (HT) plans in terms of dosimetric parameters in positron emission tomography- (PET-) computerized tomography- (CT-) based radiation therapy planning in unresectable malignant pleural mesothelioma (MPM).

  Methods: CT and coregistered PET-CT data from seven patients with histologically-proven MPM were utilized for VMAT and HT plans. Target volumes and organs at risk (OARs) were delineated. The prescription doses for planning target volume 1 (PTV1) and PTV2 were 45.0 Gy and 54 Gy in 1.8 Gy/fr, respectively. Each technique was evaluated in terms of target volume coverage and OAR doses.

  Findings: Although the maximum (p=0.001) and mean (p < 0.001) doses of PTV1, and PTV2 (p < 0.001 for maximum and p=0.001 for mean doses) favored the HT technique over VMAT, both techniques efficiently covered the target volumes. Additionally, HT also provided more homogeneous dose distribution (p < 0.001) and numerically lower doses received by most OARs, but again both rotational techniques were successful in keeping the OAR doses below the universally accepted limits. The major disadvantage of the HT technique was the requirement for longer treatment times (7.4 versus 2.5 minutes/fr; p < 0.001) to accomplish the intended treatment.

  Conclusion: Results of this dosimetric comparison clearly demonstrated the possibility of safe hemithoracic irradiation of medically/technically unresectable MPM patients with either of the two rotational RT techniques, namely the VMAT and HT. Clinically, considering their poor prognosis, these promising findings may open a potential new window for curative treatment of unresectable MPM patients, if further confirmed by future clinical studies.

  Copyright © 2019 Berrin Pehlivan et al.

• Different Cellular Response of Human Mesothelial Cell MeT-5A to Short-Term and Long-Term Multiwalled Carbon Nanotubes Exposure. L. Ju, W. Wu, M. Yu, et al. 2017;2017:2747215. PubMed · Publisher · Free full text

  Abstract

  Despite being a commercially important product, multiwalled carbon nanotubes (MWCNTs) continue to raise concerns over human health due to their structural similarity to asbestos. Indeed, exposure to MWCNT has been shown to induce lung cancer and even mesothelioma, but contradictory results also exist. To clarify the potentially carcinogenic effects of rigid and rod-like MWCNT and to elucidate the underlying mechanisms, the effects of MWCNT on human mesothelial cell MeT-5A were examined throughout 3 months of continuous exposure, including cytotoxicity, genotoxicity, and cell motility. It was found that MWCNT did not affect MeT-5A cell proliferation at 10 μg/cm2 within 72 h treatment, but under the same condition, MWCNT induced genotoxicity and perturbed cell motility. In addition, MeT-5A cells demonstrated different cellular responses to MWCNT after short-term and long-term exposure. Taken together, our results indicated a possible carcinogenic potential for MWCNT after long-term treatment, in which Annexin family proteins might be involved.

• Incidental and Underreported Pleural Plaques at Chest CT: Do Not Miss Them-Asbestos Exposure Still Exists. M.A. Mazzei, F. Contorni, F. Gentili, et al. 2017;2017:6797826. PubMed · Publisher · Free full text

  Abstract

  Pleural plaques (PPs) may be a risk factor for mortality from lung cancer in asbestos-exposed workers and are considered to be a marker of exposure. Diagnosing PPs is also important because asbestos-exposed patients should be offered a health surveillance that is mandatory in many countries. On the other hand PPs are useful for compensation purposes. In this study we aimed to evaluate the prevalence, as incidental findings, and the underreporting rate of PPs in chest CT scans (CTs) performed in a cohort of patients (1512) who underwent chest CT with a slice thickness no more than 1.25 mm. PPs were found in 76 out of 1482 patients (5.1%); in 13 out of 76 (17,1%) CTs were performed because of clinical suspicion of asbestos exposure and 5 of them (38%) were underreported by radiologist. In the remaining 63 cases (82.9%) there was no clinical suspicion of asbestos exposure at the time of CTs (incidental findings) and in 38 of these 63 patients (60.3%) PPs were underreported. Reaching a correct diagnosis of PPs requires a good knowledge of normal locoregional anatomy and rigorous technical approach in chest CT execution. However the job history of the patient should always be kept in mind.

• Combined Analysis of SNP Array Data Identifies Novel CNV Candidates and Pathways in Ependymoma and Mesothelioma. G. Wajnberg, B.S. Carvalho, C.G. Ferreira, et al. 2015;2015:902419. PubMed · Publisher · Free full text

  Abstract

  Copy number variation is a class of structural genomic modifications that includes the gain and loss of a specific genomic region, which may include an entire gene. Many studies have used low-resolution techniques to identify regions that are frequently lost or amplified in cancer. Usually, researchers choose to use proprietary or non-open-source software to detect these regions because the graphical interface tends to be easier to use. In this study, we combined two different open-source packages into an innovative strategy to identify novel copy number variations and pathways associated with cancer. We used a mesothelioma and ependymoma published datasets to assess our tool. We detected previously described and novel copy number variations that are associated with cancer chemotherapy resistance. We also identified altered pathways associated with these diseases, like cell adhesion in patients with mesothelioma and negative regulation of glutamatergic synaptic transmission in ependymoma patients. In conclusion, we present a novel strategy using open-source software to identify copy number variations and altered pathways associated with cancer.

• Endocytosis of Multiwalled Carbon Nanotubes in Bronchial Epithelial and Mesothelial Cells. K. Maruyama, H. Haniu, N. Saito, et al. 2015;2015:793186. PubMed · Publisher · Free full text

  Abstract

  Bronchial epithelial cells and mesothelial cells are crucial targets for the safety assessment of inhalation of carbon nanotubes (CNTs), which resemble asbestos particles in shape. Intrinsic properties of multiwalled CNTs (MWCNTs) are known to cause potentially hazardous effects on intracellular and extracellular pathways. These interactions alter cellular signaling and affect major cell functions, resulting in cell death, lysosome injury, reactive oxygen species production, apoptosis, and cytokine release. Furthermore, CNTs are emerging as a novel class of autophagy inducers. Thus, in this study, we focused on the mechanisms of MWCNT uptake into the human bronchial epithelial cells (HBECs) and human mesothelial cells (HMCs). We verified that MWCNTs are actively internalized into HBECs and HMCs and were accumulated in the lysosomes of the cells after 24-hour treatment. Next, we determined which endocytosis pathways (clathrin-mediated, caveolae-mediated, and macropinocytosis) were associated with MWCNT internalization by using corresponding endocytosis inhibitors, in two nonphagocytic cell lines derived from bronchial epithelial cells and mesothelioma cells. Clathrin-mediated endocytosis inhibitors significantly suppressed MWCNT uptake, whereas caveolae-mediated endocytosis and macropinocytosis were also found to be involved in MWCNT uptake. Thus, MWCNTs were positively taken up by nonphagocytic cells, and their cytotoxicity was closely related to these three endocytosis pathways.

• Functional Alteration of Natural Killer Cells and Cytotoxic T Lymphocytes upon Asbestos Exposure and in Malignant Mesothelioma Patients. Y. Nishimura, N. Kumagai-Takei, H. Matsuzaki, et al. 2015;2015:238431. Review PubMed · Publisher · Free full text

  Abstract

  Malignant mesothelioma is caused by exposure to asbestos, which is known to have carcinogenic effects. However, the development of mesothelioma takes a long period and results from a low or intermediate dose of exposure. These findings have motivated us to investigate the immunological effects of asbestos exposure and analyze immune functions of patients with mesothelioma and pleural plaque, a sign of exposure to asbestos. Here, we review our knowledge concerning natural killer (NK) cells and cytotoxic T lymphocytes (CTL). NK cells showed impaired cytotoxicity with altered expression of activating receptors upon exposure to asbestos, while induction of granzyme(+) cells in CD8(+) lymphocytes was suppressed by asbestos exposure. It is interesting that a decrease in NKp46, a representative activating receptor, is common between NK cells in PBMC culture with asbestos and those of mesothelioma patients. Moreover, it was observed that CD8(+) lymphocytes may be stimulated by some kind of "nonself" cells in plaque-positive individuals and in mesothelioma patients, whereas CTL in mesothelioma is impaired by poststimulation maintenance of cytotoxicity. These findings suggest that analysis of immunological parameters might contribute to the evaluation of health conditions of asbestos-exposed individuals and to a greater understanding of the pathology of malignant mesothelioma.

  In plain English

  This review summarized a Japanese research group's own earlier laboratory and blood studies on how asbestos may affect two kinds of killer immune cells: natural killer (NK) cells and cytotoxic T lymphocytes (CTLs). An NK cell line kept with chrysotile asbestos showed impaired killing ability after around 5 months. In blood, NK cells from 7 malignant mesothelioma patients had less of a surface receptor called NKp46 than those from 10 healthy people. Human blood cells cultured with chrysotile showed the same drop; glass wool did not cause it. Chrysotile also held back the development of killer function in CD8+ T cells in culture. Compared with 16 healthy volunteers, 16 people with pleural plaques and 14 mesothelioma patients had a higher percentage of CD8+ cells containing perforin, a cell-killing protein. After stimulation, this percentage fell in mesothelioma patients, while most healthy and plaque-positive individuals kept these cells. The authors concluded that asbestos exposure has the potential to suppress NK cell and CTL function. They said more studies were needed to tell whether CTL impairment in mesothelioma stems from the tumor or from asbestos.

  We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

• Increased Standardised Incidence Ratio of Malignant Pleural Mesothelioma in Taiwanese Asbestos Workers: A 29-Year Retrospective Cohort Study. C.K. Lin, Y.Y. Chang, J.D. Wang, et al. 2015;2015:678598. PubMed · Publisher · Free full text

  Abstract

  Objective: This paper aimed to determine the standardised incidence ratio (SIR) of malignant pleural mesothelioma (MPM) in workers exposed to asbestos in Taiwan.

  Methods: All workers employed in asbestos-related factories and registered by the Bureau of Labour Insurance between 1 March, 1950, and 31 December, 1989, were included in the study and were followed from 1 January, 1980, through 31 December, 2009. Incident cases of all cancers, including MPM (ICD-9 code: 163), were obtained from the Taiwan Cancer Registry. SIRs were calculated based on comparison with the incidence rate of the general population of Taiwan and adjusted for age, calendar period, sex, and duration of employment.

  Results: The highest SIR of MPM was found for male workers first employed before 1979, with a time since first employment more than 30 years (SIR 4.52, 95% CI: 2.25-8.09). After consideration of duration of employment, the SIR for male MPM was 5.78 (95% CI: 1.19-16.89) for the workers employed for more than 20 years in asbestos-related factories.

  Conclusions: This study corroborates the association between occupational asbestos exposure and MPM. The highest risk of MPM was found among male asbestos workers employed before 1979 and working for more than 20 years in asbestos-related factories.

• MicroRNA and mRNA features of malignant pleural mesothelioma and benign asbestos-related pleural effusion. G. Ak, S.C. Tomaszek, F. Kosari, et al. 2015;2015:635748. PubMed · Publisher · Free full text

  Abstract

  Introduction: We investigated the expression of microRNAs and mRNAs in pleural tissues from patients with either malignant pleural mesothelioma or benign asbestos-related pleural effusion.

  Methods: Fresh frozen tissues from a total of 18 malignant pleural mesothelioma and 6 benign asbestos-related pleural effusion patients were studied. Expression profiling of mRNA and microRNA was performed using standard protocols.

  Results: We discovered significant upregulation of multiple microRNAs in malignant pleural mesothelioma compared to benign asbestos-related pleural effusion. Hsa-miR-484, hsa-miR-320, hsa-let-7a, and hsa-miR-125a-5p were able to discriminate malignant from benign disease. Dynamically regulated mRNAs were also identified. MET was the most highly overexpressed gene in malignant pleural mesothelioma compared to benign asbestos-related pleural effusion. Integrated analyses examining microRNA-mRNA interactions suggested multiple altered targets within the Notch signaling pathway.

  Conclusions: Specific microRNAs and mRNAs may have diagnostic utility in differentiating patients with malignant pleural mesothelioma from benign asbestos-related pleural effusion. These studies may be particularly helpful in patients who reside in a region with a high incidence of mesothelioma.

• Diagnostic and prognostic value of soluble syndecan-1 in pleural malignancies. F. Mundt, G. Heidari-Hamedani, G. Nilsonne, et al. 2014;2014:419853. PubMed · Publisher · Free full text

  Abstract

  Background: The distinction between malignant and benign pleural effusions is a diagnostic challenge today and measuring soluble biomarkers could add to the diagnostic accuracy. Syndecan-1 is a proteoglycan involved in various cellular functions and is cleaved from the cell surface in a regulated manner. The shed fragment, which can be recovered in effusion supernatant and in serum, retains its binding capacities, but often with different functions and signalling properties than the cell-bound form.

  Aim: This study aimed to investigate the diagnostic and prognostic value of soluble syndecan-1 in pleural effusions and sera from patients with pleural malignancies.

  Study Design: Using two cohorts of patients, we assessed the diagnostic and prognostic value of soluble syndecan-1 in pleural effusions and sera, using enzyme-linked immunosorbent assays.

  Results: In pleural effusions, syndecan-1 distinguished malignant and benign diseases, with an odds ratio of 8.59 (95% CI 3.67 to 20.09). Furthermore, syndecan-1 in pleural effusions predicted a survival difference for patients with pleural metastatic disease and malignant mesothelioma of 11.2 and 9.2 months, respectively. However, no such effects were seen when syndecan-1 was measured in serum.

  Conclusion: Soluble syndecan-1 is a promising candidate biomarker for the cytopathological diagnosis and prognostication of malignant pleural effusions.

• Expression of mesothelioma-related markers in meningiomas: an immunohistochemical study. E. Abdelzaher, D.M. Abdallah. 2014;2014:968794. PubMed · Publisher · Free full text

  Abstract

  Background: Meningiomas are common intracranial tumors. Recently, histogenetic and phenotypic similarities between meningiomas and mesotheliomas have been proposed. We were interested in whether these similarities are reflected on the immunohistochemical level, which would add new potentially diagnostic markers for meningiomas.

  Methods: The expression of mesothelioma-related markers (D2-40, Calretinin, Keratin 5/6, WT1, and Methotheioma-Ab1) was investigated in 87 cases of meningiomas and compared to EMA expression.

  Results: 73.6% of meningioma cases were grade I, 20.7% were grade II, and 5.7% were grade III. 83.9% of meningioma cases were classical and 16.1% had special nonmeningothelial features. D2-40 was expressed in 37.9% of cases and was significantly restricted to classical meningiomas. Calretinin and WT1 were negative while Keratin 5/6 and Mesothelioma-Ab1 were weakly expressed in classical variants (5.7% and 3.4%, resp.). EMA was consistently expressed in all cases. Its expression was significantly higher than that of mesothelioma-related markers; this held true also when D2-40 expression was considered separately.

  Conclusions: Mesothelioma-related markers are not extensively expressed in meningiomas, a finding that argues against their proposed histogenetic and phenotypic similarities. Compared to EMA, the significantly lower expression of mesothelioma-related markers and their restricted expression to classical meningioma variants hamper their potential future use as diagnostic markers for meningioma.

• A potential therapeutic strategy for malignant mesothelioma with gene medicine. Y. Tada, H. Shimada, K. Hiroshima, et al. 2013;2013:572609. Review PubMed · Publisher · Free full text

  Abstract

  Malignant mesothelioma, closely linked with occupational asbestos exposure, is relatively rare in the frequency, but the patient numbers are going to increase in the next few decades all over the world. The current treatment modalities are not effective in terms of the overall survival and the quality of life. Mesothelioma mainly develops in the thoracic cavity and infrequently metastasizes to extrapleural organs. A local treatment can thereby be beneficial to the patients, and gene therapy with an intrapleural administration of vectors is one of the potential therapeutics. Preclinical studies demonstrated the efficacy of gene medicine for mesothelioma, and clinical trials with adenovirus vectors showed the safety of an intrapleural injection and a possible involvement of antitumor immune responses. Nevertheless, low transduction efficiency remains the main hurdle that hinders further clinical applications. Moreover, rapid generation of antivector antibody also inhibits transgene expressions. In this paper, we review the current status of preclinical and clinical gene therapy for malignant mesothelioma and discuss potential clinical directions of gene medicine in terms of a combinatory use with anticancer agents and with immunotherapy.

• Synthesis and biological evaluation of O-[3-18F-fluoropropyl]-α-methyl tyrosine in mesothelioma-bearing rodents. I.H. Shih, F.L. Kong, M.S. Ali, et al. 2013;2013:460619. PubMed · Publisher · Free full text

  Abstract

  Radiolabeled tyrosine analogs enter cancer cells via upregulated amino acid transporter system and have been shown to be superior to (18)F-fluoro-2-deoxy-D-glucose ((18)F-FDG) in differential diagnosis in cancers. In this study, we synthesized O-[3-(19)F-fluoropropyl]-α-methyl tyrosine ((19)F-FPAMT) and used manual and automated methods to synthesize O-[3-(18)F-fluoropropyl]-α-methyl tyrosine ((18)F-FPAMT) in three steps: nucleophilic substitution, deprotection of butoxycarbonyl, and deesterification. Manual and automated synthesis methods produced (18)F-FPAMT with a radiochemical purity >96%. The decay-corrected yield of (18)F-FPAMT by manual synthesis was 34% at end-of-synthesis (88 min). The decay-corrected yield of (18)F-FPAMT by automated synthesis was 15% at end-of-synthesis (110 min). (18)F-FDG and (18)F-FPAMT were used for in vitro and in vivo studies to evaluate the feasibility of (18)F-FPAMT for imaging rat mesothelioma (IL-45). In vitro studies comparing (18)F-FPAMT with (18)F-FDG revealed that (18)F-FDG had higher uptake than that of (18)F-FPAMT, and the uptake ratio of (18)F-FPAMT reached the plateau after being incubated for 60 min. Biodistribution studies revealed that the accumulation of (18)F-FPAMT in the heart, lungs, thyroid, spleen, and brain was significantly lower than that of (18)F-FDG. There was poor bone uptake in (18)F-FPAMT for up to 3 hrs suggesting its in vivo stability. The imaging studies showed good visualization of tumors with (18)F-FPAMT. Together, these results suggest that (18)F-FPAMT can be successfully synthesized and has great potential in mesothelioma imaging.

• The cytotoxic effect of magainin II on the MDA-MB-231 and M14K tumour cell lines. R. Anghel, D. Jitaru, L. Bădescu, et al. 2013;2013:831709. PubMed · Publisher · Free full text

  Abstract

  Many studies have highlighted the tumoricidal properties of some natural peptides known to have antimicrobial virtues. Also, the increasingly higher resistance to conventional antibiotics has become a global public health issue, and the need for new antibiotics has stimulated interest in finding and synthesizing new antimicrobial peptides, which may also be used as chemotherapeutic agents. Relying on the literature, the purpose of our in vitro research was to assess the tumoricidal potential of magainin II on a series of tumour cell lines, namely, MDA-MB-231 (breast adenocarcinoma) and M14K (human mesothelioma). The experimental results of our study revealed that the cytotoxic effects of magainin II depend on its concentration. Its efficiency is significant at 120 μM concentrations, and, although it is much lower, it persists even at 60 μM concentrations. The effects were insignificant at 30 μM concentrations. In our experimental research, the tumoricidal effect of magainin II was not significantly dependent on the type of tumour cell line used.

• The influence of gene-gene and gene-environment interactions on the risk of asbestosis. A. Franko, V. Dolžan, N. Arnerić, et al. 2013;2013:405743. PubMed · Publisher · Free full text

  Abstract

  This study investigated the influence of gene-gene and gene-environment interactions on the risk of developing asbestosis. The study comprised 262 cases with asbestosis and 265 controls with no asbestos-related disease previously studied for MnSOD, ECSOD, CAT, GSTT1, GSTM1, GSTP1, and iNOS polymorphisms. Data on cumulative asbestos and smoking were available for all subjects. To assess gene-gene and gene-environmental interactions, logistic regression was used. The associations between MnSOD Ala -9Val polymorphism and the risk of asbestosis and between iNOS genotypes and asbestosis were modified by CAT -262 C > T polymorphism (P = 0.038; P = 0.031). A strong interaction was found between GSTM1-null polymorphism and smoking (P = 0.007), iNOS (CCTTT) n polymorphism and smoking (P = 0.054), and between iNOS (CCTTT) n polymorphism and cumulative asbestos exposure (P = 0.037). The findings of this study suggest that the interactions between different genotypes, genotypes and smoking, and between genotypes and asbestos exposure have an important influence on the development of asbestosis and should be seriously considered in future research on occupational/environmental asbestos-related diseases.

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