Metabolic Nano-Machines: Extracellular Vesicles Containing Active Enzymes and Their Contribution to Liver Diseases
AbstractPurpose of ReviewThe field of extracellular vesicles is growing exponentially because of the important role that these extracellular organelles had on cell to cell communication, triggering a large number of review compilations focusing on different aspects of their biology. Although their importance as effectors or potential biomarkers is well covered, the highlight of extracellular vesicles as carriers of active enzymes which have the capability to transform the surrounding media is less covered by bibliographic studies. In the present review, we focus our attention on enzymatic activity carried by vesicles, with...
Source: Current Pathobiology Reports - July 16, 2019 Category: Laboratory Medicine Source Type: research

High-Resolution Microscopy for Imaging Cancer Pathobiology
AbstractPurpose of ReviewLight microscopy plays an essential role in clinical diagnosis and understanding the pathogenesis of cancer. Conventional bright-field microscope is used to visualize abnormality in tissue architecture and nuclear morphology, but often suffers from many limitations. This review focuses on the potential of new imaging techniques to improve basic and clinical research in pathobiology.Recent FindingsLight microscopy has significantly expanded its ability in resolution, imaging volume, speed, and contrast. It now allows 3D high-resolution volumetric imaging of tissue architecture from large tissue and ...
Source: Current Pathobiology Reports - July 10, 2019 Category: Laboratory Medicine Source Type: research

Next-Generation Techniques for Determination of Protein-Protein Interactions: Beyond the Crystal Structure
AbstractPurpose of ReviewWe discuss recent advancements in structural biology methods for investigating sites of protein-protein interactions. We will inform readers outside the field of structural biology about techniques beyond crystallography and how these different technologies can be utilized for drug development.Recent FindingsAdvancements in cryo-electron microscopy (cryoEM) and micro-electron diffraction (microED) may change how we view atomic resolution structural biology, such that well-ordered macrocrystals of protein complexes are not required for interface identification. However, some drug discovery applicati...
Source: Current Pathobiology Reports - June 30, 2019 Category: Laboratory Medicine Source Type: research

Breast Cancer and Dietary Intake of Endocrine Disruptors: a Review of Recent Literature
AbstractPurpose of ReviewIn women, breast cancer is the second most common cause of death. Endocrine-disrupting chemicals (EDCs) can interfere with hormone signaling, possibly linking to cancer. Among these, estrogen-mimicking endocrine disruptors (EEDs) infiltrate the human diet and are known to bind to estrogen receptors.Recent FindingsWe reviewed recent literature (n = 13 papers) examining associations between dietary intake of EEDs and breast cancer incidence. Collectively, this sample of investigations suggest a positive correlation, including bisphenol A (BPA) (0.4–4.2 μg/kg-bw/day), phytoestrogens (sum of gen...
Source: Current Pathobiology Reports - June 27, 2019 Category: Laboratory Medicine Source Type: research

Nanotherapies for Treatment of Cardiovascular Disease: a Case for Antioxidant Targeted Delivery
AbstractPurpose of ReviewCardiovascular disease (CVD) involves a broad range of clinical manifestations resulting from a dysfunctional vascular system. Overproduction of reactive oxygen and nitrogen species is causally implicated in the severity of vascular dysfunction and CVD. Antioxidant therapy is an attractive avenue for treatment of CVD-associated pathologies. Implementation of targeted nanoantioxidant therapies has the potential to overcome hurdles associated with systemic delivery of antioxidants. This review examines the currently available options for nanotherapeutic targeting CVD, and explores successful studies ...
Source: Current Pathobiology Reports - June 26, 2019 Category: Laboratory Medicine Source Type: research

Using FFPE Tissue in Genomic Analyses: Advantages, Disadvantages and the Role of Biospecimen Science
AbstractPurpose of ReviewFormalin-fixed, paraffin-embedded (FFPE) tissue blocks are considered by some to be suboptimal for Next Generation Sequencing (NGS) because, compared with fresh-frozen (FF) biospecimens, the nucleic acid obtained from them is fragmented and low in quantity, containing formalin-induced modifications and mutations. However, clinical workflows do not typically have the capability to collect FF tissue, so there is an inherent necessity to perform NGS using FFPE tissue. We review relevant literature that addresses the issue of extracting DNA from FFPE tissue biospecimens then applying it to NGS.Recent F...
Source: Current Pathobiology Reports - June 3, 2019 Category: Laboratory Medicine Source Type: research

The Impact of Pre-analytical Factors on the Reliability of miRNA Measurements
AbstractPurpose of ReviewIn this review, we highlight the importance of using standardized procedures and protocols for circulating miRNA isolation, detection, and quantification, in order to establish their role as non-invasive biomarkers in the clinical setting.Recent FindingsSpecific miRNAs have already been investigated as promising prognostic and diagnostic markers in various types of cancer. Circulating microRNAs detected in plasma are continuously and intensively explored as non-invasive prognostic and diagnostic markers in a variety of human diseases and mainly in cancer. These miRNAs are remarkably stable in biolo...
Source: Current Pathobiology Reports - May 19, 2019 Category: Laboratory Medicine Source Type: research

Biospecimen Science of Blood for Peripheral Blood Mononuclear Cell (PBMC) Functional Applications
AbstractPurpose of ReviewPeripheral blood mononuclear cells (PBMCs) are used in a wide variety of preclinical assays. Preanalytical variations can have a devastating impact on the results. In this review, we list critical preanalytical factors for PBMC-based assays to develop awareness and orientation to the types of sample preparation and storage that one may consider employing.Recent FindingsCritical factors during blood collection are the blood collection tube and anticoagulant, possible stabilizer used, and the pre-isolation blood storage temperature and time. During PBMC isolation, critical factors are the isolation m...
Source: Current Pathobiology Reports - May 10, 2019 Category: Laboratory Medicine Source Type: research

Biospecimen Science of Blood for cfDNA Genetic Analyses
AbstractPurpose of ReviewcfDNA is increasingly used for biomonitoring oncological diseases or pregnancy status by different genetic analyses. Uncontrolled pre-analytical variability impacts the quality and quantity and subsequently undermines the utility of this analyte. In this review, we summarize critical pre-analytical factors to be addressed, to avoid irreproducible results.Recent FindingscfDNA quantity and quality can be impacted by the in vivo condition of the donor and the ex vivo biospecimen handling prior to the downstream analysis. In vivo, physical and psychosocial stress, circadian rhythmicity, and age appear ...
Source: Current Pathobiology Reports - April 15, 2019 Category: Laboratory Medicine Source Type: research

Standardization of Blood Collection and Processing for the Diagnostic Use of Extracellular Vesicles
AbstractPurpose of ReviewExtracellular vesicles (EVs) are lipid membrane vesicles released by many types of cells in both health and disease. EVs can be found in most body fluids, carrying a plethora of biomolecules, including proteins, RNA, and DNA, that reflect the biomolecular composition of the tissue of origin. Parenchymal and stromal cells actively release EVs in the extracellular milieu and in circulation, providing valuable information that may be exploited for diagnostic applications. However, isolation of these EV subpopulations in circulation is extremely challenging as they are diluted within more abundant EV s...
Source: Current Pathobiology Reports - January 18, 2019 Category: Laboratory Medicine Source Type: research

Cancer Foraging Ecology: Diet Choice, Patch Use, and Habitat Selection of Cancer Cells
AbstractPurpose of ReviewHere we connect theories of diet choice, patch use, and habitat selection with cancer biology. Key and only partially answered questions include: Do cancer cells ’ uptake of nutrients conform to theory? What are the supply and total mass of resources within tumors? Can cancer cell foraging strategies provide indicators for tumor dynamics and therapies? We advocate for a new research subdiscipline of cancer foraging ecology.Recent FindingsForaging ecology studies feeding behaviors of organisms as adaptations. Virtually all of life exhibits adaptations relating to diet, patch use, and habitat selec...
Source: Current Pathobiology Reports - November 27, 2018 Category: Laboratory Medicine Source Type: research

Virotherapy as Potential Adjunct Therapy for Graft-Vs-Host Disease
AbstractPurpose of ReviewThis review discusses the pathophysiology, risk factors, and the advances in the prevention or treatment of graft-vs-host disease (GvHD) by exploiting adjunct virotherapy. In addition, nonviral adjunct therapeutic options for the prevention of GvHD in the context of allogeneic hematopoietic stem cell transplantation (allo-HSCT) are discussed. The role of oncolytic viruses to treat different HSCT-eligible hematological cancers is also considered and correlated with the issue of GvHD in the context of allo-HSCT.Recent FindingsEmerging therapies focused on the prevention or treatment of GvHD include t...
Source: Current Pathobiology Reports - November 19, 2018 Category: Laboratory Medicine Source Type: research

Life History Trade-Offs in Tumors
AbstractPurposeIn this paper, we provide an overview of a life history theory and how it applies to cancer evolution.Recent FindingsWe review the literature on trade-offs in tumors, focusing on the trade-offs among cellular proliferation, survival, and motility. Trade-offs are critical natural constraints for almost all evolutionary processes. Many ecological studies show that trade-offs among these cellular functions maintain a genetic diversity. In addition, these trade-offs are not fixed, but rather can shift depending on the ecological circumstances in the microenvironment. This can lead to selection for the cellular c...
Source: Current Pathobiology Reports - November 10, 2018 Category: Laboratory Medicine Source Type: research

Hepatic Manifestations in Glycogen Storage Disease Type III
AbstractPurpose of ReviewGlycogen storage disease type III (GSD III) is an orphan disease that mainly affects the liver, heart, and skeletal muscles. It is caused by the deficiency of glycogen debranching enzyme (GDE), resulting in accumulation of glycogen (limit dextrin) primarily in the cytoplasm. With an increase in life expectancy in patients and advances in research, long-term hepatic manifestations are being recognized. This review examines our understanding of the natural history of the hepatic manifestations of GSD III and the importance of developing definitive therapies.Recent FindingsAnimal models have shown spe...
Source: Current Pathobiology Reports - November 5, 2018 Category: Laboratory Medicine Source Type: research

Nanotechnology Enabled Inhalation of Bio-therapeutics for Pulmonary Diseases: Design Considerations and Challenges
AbstractPurpose of ReviewThis review aims to critically discuss design considerations for the development of nanoparticle-based formulations for inhalation delivery of bio-therapeutics in pulmonary diseases. We will also discuss the challenges towards clinical translation of this approach, highlighting the directions for future research.Recent FindingsNanotechnology-based inhalation delivery of bio-therapeutics in pulmonary diseases can potentially overcome the shortcomings of clinically used parenteral route. Exploration of inhalable nanoparticles for delivery of bio-therapeutics in pulmonary diseases is still at an early...
Source: Current Pathobiology Reports - October 24, 2018 Category: Laboratory Medicine Source Type: research