WHO CLASSIFICATION OF TUMOURS OF HAEMATOPOIETIC AND LYMPHOID TISSUES , WHO CLASSIFICATION OF TUMOURS OF HAEMATOPOIETIC AND LYMPHOID TISSUES , کتابخانه مرکزی دانشگاه علوم پزشکی تهران

WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues

Early studies have shown how aberrantly expressed microRNAs are a hallmark of several diseases like cancer. MicroRNA expression profiling was shown to be associated with tumour development, progression and response to therapy, suggesting their possible use as diagnostic, prognostic and predictive biomarkers. Moreover, based on the increasing number of studies demonstrating that microRNAs can function as potential oncogenes or oncosuppressor genes, with the goal to improve disease response and increase cure rates, miRNA-based anticancer therapies have recently been exploited, either alone or in combination with current targeted therapies. The advantage of using microRNA approaches is based on its ability to concurrently target multiple effectors of pathways involved in cell differentiation, proliferation and survival. Here, we review our current knowledge about the involvement of microRNAs in cancer, and their potential as diagnostic, prognostic and therapeutic tools.

https://www.embopress.org/doi/pdf/10.1002/emmm.201100209

MicroRNA dysregulation in cancer: diagnostics, monitoring and therapeutics. A comprehensive review

Long non-coding RNAs (lncRNAs) are emerging as new players in the cancer paradigm demonstrating potential roles in both oncogenic and tumor suppressive pathways. These novel genes are frequently aberrantly expressed in a variety of human cancers, however the biological functions of the vast majority remain unknown. Recently, evidence has begun to accumulate describing the molecular mechanisms by which these RNA species function, providing insight into the functional roles they may play in tumorigenesis. In this review, we highlight the emerging functional role of lncRNAs in human cancer.

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The functional role of long non-coding RNA in human carcinomas

Non-small-cell lung cancers (NSCLCs), the most common lung cancers, are known to have diverse pathological features. During the past decade, in-depth analyses of lung cancer genomes and signalling pathways have further defined NSCLCs as a group of distinct diseases with genetic and cellular heterogeneity. Consequently, an impressive list of potential therapeutic targets was unveiled, drastically altering the clinical evaluation and treatment of patients. Many targeted therapies have been developed with compelling clinical proofs of concept; however, treatment responses are typically short-lived. Further studies of the tumour microenvironment have uncovered new possible avenues to control this deadly disease, including immunotherapy.

Non-small-cell lung cancers: a heterogeneous set of diseases

Since their identification in 1994, cancer stem cells (CSCs) have been objects of intensive study. Their properties and mechanisms of formation have become a major focus of current cancer research, in part because of their enhanced ability to initiate and drive tumour growth and their intrinsic resistance to conventional therapeutics. The discovery that activation of the epithelial-to-mesenchymal transition (EMT) programme in carcinoma cells can give rise to cells with stem-like properties has provided one possible mechanism explaining how CSCs arise and presents a possible avenue for their therapeutic manipulation. Here we address recent developments in CSC research, focusing on carcinomas that are able to undergo EMT. We discuss the signalling pathways that create these cells, cell-intrinsic mechanisms that could be exploited for selective elimination or induction of their differentiation, and the role of the tumour microenvironment in sustaining them. Finally, we propose ways to use our current knowledge of the complex biology of CSCs to design novel therapies to eliminate them.

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Tackling the cancer stem cells — what challenges do they pose?

Purpose The early detection is crucial for improved outcomes in lung cancer, which remains a leading cause of cancer-erelated deaths. There is an urgent need for precise molecular biomarkers to diagnose early-stage lung cancer. To address this, we assessed the potential of integrating diverse molecular biomarkers across both plasma and sputum to improve the accuracy of diagnosis, given the heterogeneous nature of lung cancer arising from multifactorial molecular aberrations. Methods We utilized droplet digital PCR to quantify miRNAs in plasma and bacterial DNA in sputum collected from 114 lung cancer patients and 121 cancer-free smokers. The participants were randomly divided into a development cohort and a validation cohort. Logistic regression models with constrained parameters were employed to optimize a signature with the highest sensitivity and specificity for early detection of lung cancer. Results The individual plasma miRNAs and sputum bacterial biomarkers had sensitivities of 62%-71% and specificities of 61%-79% for diagnosing lung cancer. A panel of plasma miRNA or sputum bacterial biomarkers produced sensitivities of 79%-85% and specificities of 74%-82%. An integrated signature comprising two miRNAs in plasma and three bacterial biomarkers in sputum was developed in the development cohort, and it exhibited a higher sensitivity (87%) and specificity (89%) in comparison to individual biomarkers. The signature's diagnostic value was confirmed in the validation cohort, regardless of tumor stage, histological type, and demo-graphic factors. Conclusion The integration of miRNA and bacterial biomarkers across both plasma and sputum samples offered an effective approach for the diagnosis of lung cancer.

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Integrating miRNAs and Bacterial DNA for Early Detection of Lung Cancer

BACKGROUND: The potential utility of microRNA as biomarkers for early detection of cancer and other diseases is being investigated with genome-scale profiling of differentially expressed microRNA. Processes for measurement assurance are critical components of genome-scale measurements. Here, we evaluated the utility of a set of total RNA samples, designed with between-sample differences in the relative abundance of miRNAs, as process controls. RESULTS: Three pure total human RNA samples (brain, liver, and placenta) and two different mixtures of these components were evaluated as measurement assurance control samples on multiple measurement systems at multiple sites and over multiple rounds. In silico modeling of mixtures provided benchmark values for comparison with physical mixtures. Biomarker development laboratories using next-generation sequencing (NGS) or genome-scale hybridization assays participated in the study and returned data from the samples using their routine workflows. Multiplexed and single assay reverse-transcription PCR (RT-PCR) was used to confirm in silico predicted sample differences. Data visualizations and summary metrics for genome-scale miRNA profiling assessment were developed using this dataset, and a range of performance was observed. These metrics have been incorporated into an online data analysis pipeline and provide a convenient dashboard view of results from experiments following the described design. The website also serves as a repository for the accumulation of performance values providing new participants in the project an opportunity to learn what may be achievable with similar measurement processes. CONCLUSIONS: The set of reference samples used in this study provides benchmark values suitable for assessing genome-scale miRNA profiling processes. Incorporation of these metrics into an online resource allows laboratories to periodically evaluate their performance and assess any changes introduced into their measurement process.

/pdf/summarizing-performance-for-genome-scale-measurement-of-97n3iealn0.pdf

Summarizing Performance for Genome Scale Measurement of miRNA: Reference Samples and Metrics

Excerpt To the editor: In the article by Goodman and colleagues (1) on the use of gingival biopsy in the diagnosis of thrombotic thrombocytopenic purpura, the authors mention the use of lymph node ...

Sanford A. Stass

Papers

Integrating miRNAs and Bacterial DNA for Early Detection of Lung Cancer

Summarizing Performance for Genome Scale Measurement of miRNA: Reference Samples and Metrics

Lymph Node Biopsy in Thrombotic Thrombocytopenic Purpura