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Topic Review
EPR Effect for Cancer Treatment
The EPR effect was first discovered by Maeda and colleagues in solid murine tumors. The polymer-drug conjugates were i.v. administered, and 10-to-100-fold higher concentrations were achieved relative to free drug administration. The concentration of nanodrugs builds up in tumors due to the EPR effect, reaching several times higher than that of plasma due to the lack of lymphatic drainage. 
  • 1.0K
  • 23 Jun 2021
Topic Review
Selenomethionine
Selenium is an essential trace element. Although this chalcogen forms a wide variety of compounds, there are surprisingly few small-molecule organic selenium compounds (OSeCs) in biology. Besides its more prominent relative selenocysteine (SeCys), the amino acid selenomethionine (SeMet) is one example. SeMet is synthesized in plants and some fungi and, via nutrition, finds its way into mammalian cells. In contrast to its sulfur analog methionine (Met), SeMet is extraordinarily redox active under physiological conditions and via its catalytic selenide (RSeR’)/selenoxide (RSe(O)R’) couple provides protection against reactive oxygen species (ROS) and other possibly harmful oxidants. In contrast to SeCys, which is incorporated via an eloquent ribosomal mechanism, SeMet can enter such biomolecules by simply replacing proteinogenic Met. Interestingly, eukaryotes, such as yeast and mammals, also metabolize SeMet to a small family of reactive selenium species (RSeS). Together, SeMet, proteins containing SeMet and metabolites of SeMet form a powerful triad of redox-active metabolites with a plethora of biological implications. In any case, SeMet and its family of natural RSeS provide plenty of opportunities for studies in the fields of nutrition, aging, health and redox biology. 
  • 791
  • 23 Jun 2021
Topic Review
Aurora Kinase B in Cancer
Aurora kinase B (AURKB) is a mitotic serine/threonine protein kinase that belongs to the aurora kinase family along with aurora kinase A (AURKA) and aurora kinase C (AURKC). AURKB is a member of the chromosomal passenger protein complex and plays a role in cell cycle progression.
  • 979
  • 23 Jun 2021
Topic Review
Thrombospondin-1 in the Tumor Microenvironment
The identification of thrombospondin-1 as an angiogenesis inhibitor in 1990 prompted interest in its role in cancer biology and potential as a therapeutic target. Decreased thrombospondin-1 mRNA and protein expression are associated with progression in several cancers, while expression by nonmalignant cells in the tumor microenvironment and circulating levels in cancer patients can be elevated. THBS1 is not a tumor suppressor gene, but the regulation of its expression in malignant cells by oncogenes and tumor suppressor genes mediates some of their effects on carcinogenesis, tumor progression, and metastasis. In addition to regulating angiogenesis and perfusion of the tumor vasculature, thrombospondin-1 limits antitumor immunity by CD47-dependent regulation of innate and adaptive immune cells. Conversely, thrombospondin-1 is a component of particles released by immune cells that mediate tumor cell killing. Thrombospondin-1 differentially regulates the sensitivity of malignant and nonmalignant cells to genotoxic stress caused by radiotherapy and chemotherapy. 
  • 854
  • 23 Jun 2021
Topic Review
Diffuse Large B-Cell Lymphomas
Diffuse large B-cell lymphoma (DLBCL) is the commonest form of lymphoid malignancy, with a prevalence of about 40% worldwide. The term DLBCL reflects the growth pattern and size of the neoplastic cells, which tend to diffusely efface the normal structure of the involved organ (most frequently the lymph node) and are provided with a diameter at least twice that of normal lymphocytes. Although during the last few years several distinct clinical-pathological categories of DLBCL have been reported in the literature, which are nowadays listed in the Revised 4th Edition of the WHO Classification of the Tumours of Haematopoietic and Lymphoid Tissues, about 80% of DLBCLs do not enter into any of these categories and are therefore termed not otherwise specified (NOS). DLBCL-NOS displays a quite variable morphology and only rarely consists of only one cytotype (centroblastic, immunoblastic or anaplastic). Thus, microscopic examination fails to define the cell of origin, prognostic indicators and novel potential therapeutic targets. The standard of care  is the immuno-chemotherapy R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), which cures up to 65% of patients. The remaining individuals with DLBCL-NOS experience resistant or relapsing disease and eventually die of it. This situation has promoted a huge number of studies focusing on the pathobiology of the tumour and based on high-throughput techniques, including gene expression profiling and next generation sequencing. In addition, attention has been focused on the mcroenvironmental composition, which can influence the behaviour and response to therapy of the tumour in conjunction with the molecular characteristics of neoplastic cells. The aim of the present review is to discuss the most recent acquisitions in the field of DLBCL-NOS based on the extensive application of molecular techniques, which paves the way to a more rational classification of the tumour along with the identification of effective prognostic indicators and novel therapeutic targets for  ad hoc personalised approaches. 
  • 584
  • 23 Jun 2021
Topic Review
Thyroid Cancer Stem-Like Cells
Thyroid cancer (TC) is the most common endocrine malignancy. Recent progress in thyroid cancer biology revealed a certain degree of intratumoral heterogeneity, highlighting the coexistence of cellular subpopulations with distinct proliferative capacities and differentiation abilities. Among those subpopulations, cancer stem-like cells (CSCs) are hypothesized to drive TC heterogeneity, contributing to its metastatic potential and therapy resistance. CSCs principally exist in tumor areas with specific microenvironmental conditions, the so-called stem cell niches. In particular, in thyroid cancer, CSCs’ survival is enhanced in the hypoxic niche, the immune niche, and some areas with specific extracellular matrix composition.
  • 507
  • 23 Jun 2021
Topic Review
EVs in HPV Infection
Since their description, extracellular vesicles (EVs) have shown growing relevance in cancer progression. These cell structures contain and transfer molecules such as nucleic acids (including DNA and RNA), proteins, and lipids. Despite the rising information about EVs’ relationship with cancer, there is still scarce evidence about their content and function in cervical cancer. Interestingly, the composition and purposes of some cellular molecules and the expression of oncogenic proteins packaged in EVs seem modified in HPV-infected cells; and, although only the E6 oncogenic protein has been detected in exosomes from HPV-positive cells, both E6/E7 oncogenes mRNA has been identified in EVs; however, their role still needs to be clarified. Given that EVs internalizing into adjacent or distant cells could modify their cellular behavior or promote cancer-associated events like apoptosis, proliferation, migration, or angiogenesis in receptor cells, their comprehensive study will reveal EV-associated mechanisms in cervical cancer. 
  • 370
  • 23 Jun 2021
Topic Review
Small-Molecule Inhibitors Targeting Proteasome-Associated Deubiquitinases
The 26S proteasome is the principal protease for regulated intracellular proteolysis. This multi-subunit complex is also pivotal for clearance of harmful proteins that are produced throughout the lifetime of eukaryotes. Recent structural and kinetic studies have revealed a multitude of conformational states of the proteasome in substrate-free and substrate-engaged forms. These conformational transitions demonstrate that proteasome is a highly dynamic machinery during substrate processing that can be also controlled by a number of proteasome-associated factors. Essentially, three distinct family of deubiquitinases–USP14, RPN11, and UCH37–are associated with the 19S regulatory particle of human proteasome. USP14 and UCH37 are capable of editing ubiquitin conjugates during the process of their dynamic engagement into the proteasome prior to the catalytic commitment. In contrast, RPN11-mediated deubiquitination is directly coupled to substrate degradation by sensing the proteasome’s conformational switch into the commitment steps. 
  • 499
  • 23 Jun 2021
Topic Review
Extracellular Vesicles in Hepatocellular Carcinoma
Extracellular vesicles (EVs) are defined as lipid bilayer particles naturally released from cells into the extracellular space. EVs have attracted interest as mediators of intercellular communication following the discovery that EVs contain RNA molecules, including non-coding RNA (ncRNA).Growing evidence for the enrichment of peculiar RNA species in specific EV subtypes has been demonstrated. ncRNAs, transferred from donor cells to recipient cells, confer to EVs the feature to regulate the expression of genes involved in differentiation, proliferation, apoptosis, and other biological processes. These multiple actions require accuracy in the isolation of RNA content from EVs and the methodologies used play a relevant role. In the liver, EVs play a crucial role in regulating cell-cell communications and several pathophysiological events in the heterogeneous liver class of cells via horizontal transfer of their cargo.
  • 460
  • 23 Jun 2021
Topic Review
Fluorescent Protein-Based Autophagy Biosensors
Autophagy is an important cellular process of self-degradation for dysfunctional or unnecessary molecules and organelles, thus dysregulation of autophagy can be involved in various diseases such as neurodegenerative diseases. To understand complex process of autophagy and the related diseases, various methods have been developed, for example biochemical, chemical, and imaging assays. In particular, fluorescent protein (FP)-based autophagy biosensors allow sensitive and selective monitoring of autophagy progression in live cells. After the discovery of green fluorescent protein (GFP), a variety of FPs has been discovered and engineered which have different physicochemical properties, such as excitation/emission spectra, Stokes shift, maturation rate, stability, photo-reactivity and pH-sensitivity. Advances in fluorescent protein technology and FP-based biosensors enabled the real-time monitoring of cellular and molecular events in live cells with high spatiotemporal resolutions.
  • 1.4K
  • 22 Jun 2021
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