NUT Midline Carcinoma
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NUT Midline Carcinoma
NUT carcinoma (NC; formerly NUT midline carcinoma (NMC)) is a rare genetically defined, very aggressive squamous cell epithelial cancer that usually arises in the midline of the body and is characterized by a chromosomal rearrangement in the nuclear protein in testis gene (i.e. ''NUTM1'' gene). In approximately 75% of cases, the coding sequence of ''NUTM1'' in band 14 on the long (or "q") arm of chromosome 15 is fused to '' BRD4'' or '' BRD3'', which creates a chimeric gene that encodes the ''BRD-NUT'' fusion protein. The remaining cases, the fusion of NUTM1 is to an unknown partner gene, usually called ''NUT''-variant. The name NUT carcinoma was introduced as the carcinoma does not only occur in the body midline; therefore, WHO also changed the name in 2015 in the WHO Classification of Tumours of the Lung, Pleura, Thymus and Heart. Signs and symptoms In the United States, about 20–30 cases are reported each year. This may be a gross underestimate of the total number of cases ...
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Micrograph
A micrograph or photomicrograph is a photograph or digital image taken through a microscope or similar device to show a magnified image of an object. This is opposed to a macrograph or photomacrograph, an image which is also taken on a microscope but is only slightly magnified, usually less than 10 times. Micrography is the practice or art of using microscopes to make photographs. A micrograph contains extensive details of microstructure. A wealth of information can be obtained from a simple micrograph like behavior of the material under different conditions, the phases found in the system, failure analysis, grain size estimation, elemental analysis and so on. Micrographs are widely used in all fields of microscopy. Types Photomicrograph A light micrograph or photomicrograph is a micrograph prepared using an optical microscope, a process referred to as ''photomicroscopy''. At a basic level, photomicroscopy may be performed simply by connecting a camera to a microscope ...
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Head
A head is the part of an organism which usually includes the ears, brain, forehead, cheeks, chin, eyes, nose, and mouth, each of which aid in various sensory functions such as sight, hearing, smell, and taste. Some very simple animals may not have a head, but many bilaterally symmetric forms do, regardless of size. Heads develop in animals by an evolutionary trend known as cephalization. In bilaterally symmetrical animals, nervous tissue concentrate at the anterior region, forming structures responsible for information processing. Through biological evolution, sense organs and feeding structures also concentrate into the anterior region; these collectively form the head. Human head The human head is an anatomical unit that consists of the skull, hyoid bone and cervical vertebrae. The term "skull" collectively denotes the mandible (lower jaw bone) and the cranium (upper portion of the skull that houses the brain). Sculptures of human heads are generally b ...
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Histone Deacetylase Inhibitor
Histone deacetylase inhibitors (HDAC inhibitors, HDACi, HDIs) are chemical compounds that inhibit histone deacetylases. HDIs have a long history of use in psychiatry and neurology as mood stabilizers and anti-epileptics. More recently they are being investigated as possible treatments for cancers, parasitic and inflammatory diseases. Cellular biochemistry/pharmacology To carry out gene expression, a cell must control the coiling and uncoiling of DNA around histones. This is accomplished with the assistance of histone acetyl transferases (HAT), which acetylate the lysine residues in core histones leading to a less compact and more transcriptionally active euchromatin, and, on the converse, the actions of histone deacetylases (HDAC), which remove the acetyl groups from the lysine residues leading to the formation of a condensed and transcriptionally silenced chromatin. Reversible modification of the terminal tails of core histones constitutes the major epigenetic mechanism for re ...
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BET Inhibitors
BET inhibitors are a class of drugs that reversibly bind the bromodomains of BET protein, Bromodomain and Extra-Terminal motif (BET) proteins BRD2, BRD3, BRD4, and BRDT, and prevent protein-protein interaction between BET proteins and acetylated histones and transcription factors. Discovery and development Thienodiazepine BET inhibitors were discovered by scientists at Yoshitomi Pharmaceuticals (now Mitsubishi Tanabe Pharma) in the early 1990s, and their potential both as anti-inflammatories and anti-cancer agents noted. However, these molecules remained largely unknown until 2010 when both the use of JQ1 in NUT midline carcinoma and of I-BET 762 in sepsis were published. Since this time a number of molecules have been described that are capable of targeting BET bromodomains. BET inhibitors have been described that are able to discriminate between the first and second bromodomains of BET proteins (BD1 vs BD2). However, no BET inhibitor has yet been described that can reliably di ...
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NUT Gene
Nut often refers to: * Nut (fruit), fruit composed of a hard shell and a seed, or a collective noun for dry and edible fruits or seeds * Nut (hardware), fastener used with a bolt Nut or Nuts may also refer to: Arts, entertainment, and media Comics * ''Nuts'', comic in the National Lampoon by Gahan Wilson (1970s) * ''Nuts'', comic strip in alternative newspapers by M. Wartella (1990s) Fictional characters * Nut (Marvel Comics), fictional character evoking the Egyptian sky goddess * Nut (movie character), character portrayed by Shing Fui-On in two late 20th-century Hong Kong crime films Films * ''Nuts'' (1987 film), American drama * ''Nuts'' (2012 film), French comedy * ''Nuts!'' (film), animated documentary on John R. Brinkley Television * John Acorn, the "nature nut" in series ''Acorn, The Nature Nut'' *NBC Universal Television Studio, or NUTS, former name of television arm of NBCUniversal / Universal Television * Nuts TV, British television channel related to ''Nuts'' ...
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Chromosomal Translocation
In genetics, chromosome translocation is a phenomenon that results in unusual rearrangement of chromosomes. This includes balanced and unbalanced translocation, with two main types: reciprocal-, and Robertsonian translocation. Reciprocal translocation is a chromosome abnormality caused by exchange of parts between non-homologous chromosomes. Two detached fragments of two different chromosomes are switched. Robertsonian translocation occurs when two non-homologous chromosomes get attached, meaning that given two healthy pairs of chromosomes, one of each pair "sticks" and blends together homogeneously. A gene fusion may be created when the translocation joins two otherwise-separated genes. It is detected on cytogenetics or a karyotype of affected cells. Translocations can be balanced (in an even exchange of material with no genetic information extra or missing, and ideally full functionality) or unbalanced (where the exchange of chromosome material is unequal resulting in extr ...
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Immunohistochemistry
Immunohistochemistry (IHC) is the most common application of immunostaining. It involves the process of selectively identifying antigens (proteins) in cells of a tissue section by exploiting the principle of antibodies binding specifically to antigens in biological tissues. IHC takes its name from the roots "immuno", in reference to antibodies used in the procedure, and "histo", meaning tissue (compare to immunocytochemistry). Albert Coons conceptualized and first implemented the procedure in 1941. Visualising an antibody-antigen interaction can be accomplished in a number of ways, mainly either of the following: * ''Chromogenic immunohistochemistry'' (CIH), wherein an antibody is conjugated to an enzyme, such as peroxidase (the combination being termed immunoperoxidase), that can catalyse a colour-producing reaction. * ''Immunofluorescence'', where the antibody is tagged to a fluorophore, such as fluorescein or rhodamine. Immunohistochemical staining is widely used in the ...
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CD34
CD34 is a transmembrane phosphoglycoprotein protein encoded by the CD34 gene in humans, mice, rats and other species. CD34 derives its name from the cluster of differentiation protocol that identifies cell surface antigens. CD34 was first described on hematopoietic stem cells independently by Civin et al. and Tindle et al. as a cell surface glycoprotein and functions as a cell-cell adhesion factor. It may also mediate the attachment of hematopoietic stem cells to bone marrow extracellular matrix or directly to stromal cells. Clinically, it is associated with the selection and enrichment of hematopoietic stem cells for bone marrow transplants. Due to these historical and clinical associations, CD34 expression is almost ubiquitously related to hematopoietic cells; however, it is actually found on many other cell types as well. Function The CD34 protein is a member of a family of single-pass transmembrane sialomucin proteins that show expression on early haematopoietic and v ...
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Carcinoembryonic Antigen
Carcinoembryonic antigen (CEA) describes a set of highly related glycoproteins involved in cell adhesion. CEA is normally produced in gastrointestinal tissue during fetal development, but the production stops before birth. Consequently, CEA is usually present at very low levels in the blood of healthy adults (about 2–4 ng/mL). However, the serum levels are raised in some types of cancer, which means that it can be used as a tumor marker in clinical tests. Serum levels can also be elevated in heavy smokers. CEA are glycosyl phosphatidyl inositol (GPI) cell-surface-anchored glycoproteins whose specialized sialo fucosylated glycoforms serve as functional colon carcinoma L-selectin and E-selectin ligands, which may be critical to the metastatic dissemination of colon carcinoma cells. Immunologically they are characterized as members of the CD66 cluster of differentiation. The proteins include CD66a, CD66b, CD66c, CD66d, CD66e, CD66f. History CEA was first identi ...
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TP63
Tumor protein p63, typically referred to as p63, also known as transformation-related protein 63 is a protein that in humans is encoded by the ''TP63'' (also known as the '' p63'') gene. The ''TP63'' gene was discovered 20 years after the discovery of the '' p53'' tumor suppressor gene and along with '' p73'' constitutes the ''p53'' gene family based on their structural similarity. Despite being discovered significantly later than ''p53'', phylogenetic analysis of ''p53'', ''p63'' and ''p73'', suggest that ''p63'' was the original member of the family from which ''p53'' and ''p73'' evolved. Function Tumor protein p63 is a member of the p53 family of transcription factors. p63 -/- mice have several developmental defects which include the lack of limbs and other tissues, such as teeth and mammary glands, which develop as a result of interactions between mesenchyme and epithelium. TP63 encodes for two main isoforms by alternative promoters (TAp63 and ΔNp63). ΔNp63 is involved ...
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Cytokeratin
Cytokeratins are keratin proteins found in the intracytoplasmic cytoskeleton of epithelial tissue. They are an important component of intermediate filaments, which help cells resist mechanical stress. Expression of these cytokeratins within epithelial cells is largely specific to particular organs or tissues. Thus they are used clinically to identify the cell of origin of various human tumors. Naming The term ''cytokeratin'' began to be used in the late 1970s, when the protein subunits of keratin intermediate filaments inside cells were first being identified and characterized. In 2006 a new systematic nomenclature for mammalian keratins was created, and the proteins previously called ''cytokeratins'' are simply called ''keratins'' (human epithelial category). For example, cytokeratin-4 (CK-4) has been renamed keratin-4 (K4). However, they are still commonly referred to as cytokeratins in clinical practice. Types There are two categories of cytokeratins: the acidic type I cy ...
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Mediastinum
The mediastinum (from ) is the central compartment of the thoracic cavity. Surrounded by loose connective tissue, it is an undelineated region that contains a group of structures within the thorax, namely the heart and its vessels, the esophagus, the trachea, the phrenic and cardiac nerves, the thoracic duct, the thymus and the lymph nodes of the central chest. Anatomy The mediastinum lies within the thorax and is enclosed on the right and left by pleurae. It is surrounded by the chest wall in front, the lungs to the sides and the spine at the back. It extends from the sternum in front to the vertebral column behind. It contains all the organs of the thorax except the lungs. It is continuous with the loose connective tissue of the neck. The mediastinum can be divided into an upper (or superior) and lower (or inferior) part: * The superior mediastinum starts at the superior thoracic aperture and ends at the thoracic plane. * The inferior mediastinum from this level ...
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