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BFM


Glossaire des marqueurs tumoraux
Définitions ('Scope Notes' de Medline)


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A

Acid Phosphatase
An enzyme that catalyses the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate. Note: prostate-specific acid phosphatase (PROSTATE + ACID PHOSPHATASE) . Ortho-phosphoric-monoester phosphohydrolase
Actins
Filamentous proteins that are the main constituent of the thin filaments of muscle fibers. The filaments (known also as filamentous or F-actin) can be dissociated into their globular subunits; each subunit is composed of a single polypeptide 375 amino acids long. This is known as globular or G-actin. In conjunction with myosin, actin is responsible for the contraction and relaxation of muscle
Acute-Phase Proteins
Proteins that are secreted into the blood in increased or decreased quantities by hepatocytes in response to trauma, inflammation, or disease. These proteins can serve as inhibitors or mediators of the inflammatory processes. Certain acute-phase proteins have been used to diagnose and follow the course of diseases or as tumor markers. Note: blood proteins
Alkaline Phosphatase
An enzyme that catalyses the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate. Ortho-phosphoric-monoester phosphohydrolase
Alpha 1-Antichymotrypsin
Glycoprotein found in alpha(1)-globulin region in human serum. It inhibits chymotrypsin-like proteinases in vivo and has cytotoxic killer-cell activity in vitro. The protein also has a role as an acute-phase protein and is active in the control immunologic and inflammatory processes, and as a tumor marker. It is a member of the serpin superfamily. Note: a serpin & acute-phase protein. Pharmacologic action: serine proteinase inhibitors
Alpha-fetoproteins
The first alpha-globulins to appear in mammalian sera during development of the embryo and the dominant serum proteins in early embryonic life. They reappear in the adult serum during certain pathologic states, primarily hepatocellular carcinoma
Alpha-Macroglobulins
Glycoproteins with a molecular weight of approximately 620,000 to 680,000. Precipitation by electrophoresis is in the alpha region. They include alpha 1-macroglobulins and alpha 2-macroglobulins. These proteins exhibit trypsin-, chymotrypsin-, thrombin-, and plasmin-binding activity and function as hormonal transporters
Alternative Splicing
A process whereby multiple protein isoforms are generated from a single gene. Alternative splicing involves the splicing together of nonconsecutive exons during the processing of some, but not all, transcripts of the gene. Thus a particular exon may be connected to any one of several alternative exons to form messenger RNA. The alternative forms produce proteins in which one part is common while the other part is different. NOTE: a form of RNA splicing where multiple protein isoforms are generated from a single gene
Androgen-binding proteins
Carrier proteins produced in the Sertoli cells of the testis, secreted into the seminiferous tubules, and transported via the efferent ducts to the epididymis. Participate in the transport of androgens; include also synthetic androgens binding proteins
Aneuploidy
The chromosomal constitution of cells which deviate from the normal by the addition or substraction of chromosomes or chromosome pairs. In a normally diploid cell the loss of a chromosome pair is termed nullisomy , the loss of a single chromosome is monosomy, the addition of a chromosome pair is tetrasomy, the addition of a single chromosome is trisomy. Note: chromosome aberration
Angiogenesis factor
Substance causing proliferation of new blood vessels. It is found in tissues with high metabolic requirements, such as the retina, and in certain cancers. The factor is also released by hypoxic macrophages at the edges or outer surfaces of wounds and initiates revascularization in wound healing. NOTE: a growth factor
Angiotensins
Oligopeptides ranging in size from angiotensin precursors with 14 amino acids to the active vasoconstrictor angiotensin II with 8 amino acids, or their analogs or derivatives. The amino acid content varies with the species and changes in that content produce antagonistic or inactive compounds. NOTE: neurotransmitters; "angiotensin" not specified as I, II or III is probably ANGIOTENSIN II but check text
Ankyrins
A family of membrane-associated proteins responsible for the attachment of the cytoskeleton. Note: membrane proteins
Antibodies, Neoplasm
Immunoglobulins induced by antigens specific for tumors other than the normally occuring histocompatibility antigens
Antigens, CD
Differentiation antigens residing on human leukocytes. CD stands for cluster of differentiation, which refers to groups of monoclonal antibodies that show similiar reactivity with certain subpopulations of antigens. The subpopulations of antigens are also known by the same CD designation
Antigens, CD14
Glycolipid-anchored membrane glycoproteins expressed on cells of the myelomonocyte lineage including monocytes, macrophages, and some granulocytes. They function as receptors for the complex of lipopolysaccharide (LPS) and LPS-binding protein. NOTE: myelomonocytic differentiation antigen
Antigens, CD15
Carbohydrate antigen which is accumulated in various human cancer tissues and secreted into the blood stream. The carbohydrate moiety can be further modified with fucose or sialic acid. Monoclonal antibodies have been determined which can discriminate each subgroup of this antigen in the sera of cancer patients. Sialyl SSEA-1 antigen is particularly elevated in the sera of patients with a variety of tumors. NOTE: carbohydrate tumor-assoc antigen.
Antigens, CD30
Differentiation antigens normally present in a small number of cells in the lymph nodes and tonsils in vivo, but also capable of being induced in a wide range of cells in vitro. They are clinically useful as tumor markers for Ki-1 lymphoma (LYMPHOMA, LARGE-CELL, KI-1) and some cases of LYMPHOMATOID PAPULOSIS, MYCOSIS FUNGOIDES, and HODGKIN'S DISEASE.
Antigens, CD31
Cell adhesion molecules present on virtually all monocytes, platelets, and granulocytes. CD31 is highly expressed on endothelial cells and concentrated at the junctions between them.
Antigens, CD40
Differentiation antigens found on all mature B-lymphocytes and some epithelial cells, carcinomas, and lymphoid dendritic cells. This is a member of the TUMOR NECROSIS FACTOR superfamily. Evidence suggests that CD40-dependent activation of B-cells is important for generation of memory B-cells within the germinal centers. NOTE: B-lymphocyte differentiation antigens
Antigens, CD44
Acidic sulfated integral membrane glycoproteins expressed in several alternatively spliced and variable glycosylated forms on a wide variety of cell types including mature T-cells, B-cells, medullary thymocytes, granulocytes, macrophages, erythrocytes and fibroblasts. CD44 antigens are the principle cell surface receptors for hyaluronate and this interaction mediates binding of lymphocytes to high endothelial venules. Note: lymphocyte homing receptors
Antigens, CD55
Glycoproteins broadly distributed among hematopoietic and non-hematopoietic cells. CD55 prevents the assembly of C3 convertase or accelerates the disassembly of preformed convertase, thus blocking the formation of the membrane attack complex. NOTE: differentiation antigens
Antigens, CD58
Glycoproteins with a wide distribution on hematopoietic and non-hematopoietic cells and strongly expressed on macrophages. CD58 mediates cell adhesion by binding to CD2 (ANTIGENS, CD2) and this enhances antigen-specific T-cell activation. NOTE: differentiation antigens
Antigens, CD59
Small glycoproteins found on both hematopoietic and non-hematopoietic cells. CD59 restricts the cytolytic activity of homologous complement by binding to C8 and C9 and blocking the assembly of the membrane attack complex. (From Barclay et al., The Leukocyte Antigen FactsBook, 1993, p234). NOTE: differentiation antigens
Antigens, CD80
The natural ligand for the T-cell antigen CD28 (ANTIGENS, CD28) mediating T- and B-cell adhesion. CD80 is expressed on activated B-cells and gamma-interferon-stimulated monocytes. The binding of CD80 to CD28 and CTLA-4 provides a co-stimulatory signal to T-cells and leads to greatly upregulated lymphokine production. NOTE: differentiation antigens
Antigens, CD95
Differentiation antigens expressed on a variety of cell lines including myeloid and lymphoblastoid cell lines. Their primary role is to regulate peripheral immune responses, which is achieved by triggering APOPTOSIS. NOTE: differentiation antigens; in X ref FAS ANTIGENS, fas stands for Folic Acid Synthesis
Antigens, differentiation
Antigens expressed primarily on the membranes of living cells during sequential stages of maturation and differentiation. As immunologic markers they have high organ and tissue specificity and are useful as probes in studies of normal cell development as well as neoplastic transformation
Antigens, Neoplasm
Proteins, glycoprotein, or lipoprotein moieties on surfaces of tumor cells that are usually identified by monoclonal antibodies. Many of these are of either embryonic or viral origin
Antigens, Surface
Antigens on surfaces of cells, including infectious or foreign cells or viruses. They are usually protein-containing groups on cell membranes or walls and may be isolated
Antigens, Tumor-Associated, Carbohydrate
Carbohydrate antigens expressed by malignant tissue. They are useful as tumor markers and are measured in the serum by means of a radioimmunoassay employing monoclonal antibodies
Antigens, Viral, Tumor
Those proteins recognized by antibodies from serum of animals bearing tumors induced by virus; these proteins are presumably coded for by the nucleic acids of the same viruses that caused the neoplastic transformation
Apoptosis
One of the two mechanisms by which CELL DEATH occurs (the other being the pathological process of NECROSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA FRAGMENTATION) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. NOTE: the physiol mechanism of cell death
Aromatase
An enzyme which converts androgens to estrogens by desaturating ring A of the steroid. This enzyme complex is located in the endoplasmic reticulum of estrogen-producing cells including ovaries, placenta, testicular Sertoli and Leydig cells, adipose, and brain tissues. The enzyme complex has two components, one of which is the CYP19 gene product, the aromatase cytochrome P-450. The other component is NADPH-cytochrome P-450 reductase which transfers reducing equivalents to P-450(arom). NOTE: a cytochrome P-450 enzyme
Aspartate Aminotransferase
An enzyme of the transferase class that catalyzes the reaction of L-aspartate and 2-ketoglutarate to yield oxaloacetate and L-glutamate. The enzyme is a pyridoxal phosphate protein. In the liver the reaction transfers excess metabolic nitrogen into aspartate for disposal in the urea cycle. The enzyme occurs also in the cytoplasm and mitochondria of most cells and is released into the blood in tissue damage. Elevation in serum aspartate aminotransferase (SGOT) activity is used as a diagnostic test. (From Dorland, 27th ed)
Autocrine motility factor
A member of the class of cytokines secreted by tumor cells. It elicits increases in cell motility and phosphoinositide metabolism in the secreting or producing cell via a pertussis toxin-sensitive G-protein signal transduction pathway. The factor has also been used as a marker for bladder cancer. NOTE: "secreted by tumor cells"

B

Biological Factors
Compounds made by living organisms. They have biological or physiological activities
Biological markers
Measurable and quantifiable biological parameters (e.g., specific enzyme concentration, specific hormone concentration, specific gene phenotype distribution in a population, presence of biological substances) which serve as indices for health- and physiology-related assessments, such as disease risk, psychiatric disorders, environmental exposure and its effects, disease diagnosis, metabolic processes, substance abuse, pregnancy, cell line development, epidemiologic studies, etc.
Bombesin
A tetradecapeptide originally obtained from the skins of toads Bombina bombina and B. variegata. It is also an endogenous neurotransmitter in many animals including mammals. Bombesin affects vascular and other smooth muscle, gastric secretion, and renal circulation and function. NOTE: a neurotransmitter
Bradykinin
A nonapeptide messenger that is enzymatically produced from kallidin in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from mast cells during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. NOTE: a neurotransmitter
BRCA1 Protein
Phosphoprotein encoded by the BRCA1 gene (GENES, BRCA1). It has limited sequence similarity with known proteins. In normal cells the BRCA1 protein is localized in the nucleus, whereas in the majority of breast cancer cell lines and in malignant pleural effusions from breast cancer patients, it is localized mainly in the cytoplasm. (Science 1995;270(5237):713,789-91). NOTE: in normal cell nucleus & in BReast CAncer cell cytoplasm

C

CA-125 Antigen
Carbohydrate antigen most commonly seen in tumors of the ovary and occasionally seen in breast, kidney, and gastrointestinal tract tumors and normal tissue. CA 125 is clearly tumor-associated but not tumor-specific. NOTE: a carbohydrate antigen assoc with various tumors but also normal tissue; CA stands for Cancer-Associated
CA-15-3 Antigen
Carbohydrate antigen elevated in patients which tumor of the breast, ovary, lung and prostate as well as other disorders. Note: a carbohydrate antigen associated with various tumors and other diseases; CA stands for Cancer-Associated
CA-19-9 Antigen
Sialylated Lewis blood group carbohydrate antigen found in many adenocarcinomas of the digestive tract, especially pancreatic tumors. NOTE: a carbohydrate antigen assoc with digestive tract cancer; CA stands for Cancer-Associated
Cadherins
A group of functionally related glycoproteins responsible for the calcium-dependent cell-to-cell adhesion mechanism. They are divided into subclasses E-, P-, and N-cadherins, which are distinct in immunological specificity and tissue distribution. They promote cell adhesion via an homophilic mechanism. These compounds play a role in the construction of tissues and of the whole animal body. Note: glycoproteins in calcium-dependent cell-to-cell adhesion, the action being the source of the name: Calcium-dependent ADHesion
Calcitonin
A peptide hormone that lowers calcium concentration in the blood. In humans, it is released by thyroid cells and acts to decrease the formation and absorptive activity of osteoclasts. Its role in regulating plasma calcium is much greater in children and in certain diseases than in normal adults. NOTE: a neurotransmitter hormone
Calcitriol
(1 alpha,3 beta, 5Z,7E)-9,10-Secocholesta-5,7,10(19)-triene-1,3,25-triol). The physiologically active form of vitamin D. It is formed in kidney by enzymatic hydroxylation of 25-hydroxycholecalciferol (calcifediol) and its production is stimulated by low blood calcium levels and parathyroid hormone. Calcitriol increases intestinal absorption of calcium and phosphorus and in concert with parathyroid hormone increases bone resorption. It is used in the treatment of chronic kidney failure, hypoparathyroidism, osteomalacia, and osteoporosis. NOTE: a physiol active form of vitamin D
Calcium-Binding Proteins
Proteins to which calcium ions are bound. They can act as transport proteins, regulator proteins or activator proteins
Calmodulin-Dependent Protein Kinases
A group of enzymes that catalyzes the phosphorylation of proteins. They are dependent on calmodulin and sometimes calcium. A wide range of proteins can act as acceptor, including vimentin, synapsin, glycogen synthase, myosin light chains, and the microtubule-associated proteins. (From Enzyme Nomenclature, 1992, p277)
Carcinoembryonic antigen
Serum glycoprotein secreted into the glycocalyx coating the luminal surface of the gastrointestinal epithelia. Originally thought to be a specific antigen of the fetal digestive tract and adenocarcinoma of the colon, CEA is now known to occur normally in feces and pancreaticobiliary secretions and to appear in the plasma in a diverse group of neoplastic and non-neoplastic conditions. The primary use of CEA is in monitoring response to treatment of colorectal cancer. (From Dorland, 28th ed) CEA and other members of the CEA family appear to mediate intercellular adhesion. NOTE: Data Form: CEA
Carrier Proteins
Transport proteins that carry specific substances in the blood or across cell membranes
cdc28 protein kinase
A protein kinase encoded by the Saccharomyces cerevisiae CDC28 gene and required for progression from the G1 to the S phase in the cell cycle. It is a complex of approximately 160 kD containing a substrate called p40. (Cell 1988 Sep 23;54(7):1061)
Cell Adhesion
Adherence of cells to surfaces or other cells
Cell Adhesion Molecules
Surface ligands, usually glycoproteins, that mediate cell-to-cell adhesion. Their functions include the assembly and interconnection of various vertebrate systems, as well as maintenance of tissue integration, wound healing, morphogenic movements, cellular migrations, and metastasis
Cell cycle
The complex series of phenomena, occurring between the end of one cell division and the end of the next, by which cellular material is divided between daughter cells
Cell cycle proteins
Proteins that control the cell division cycle. This family of proteins includes a wide variety of classes, including CYCLIN-DEPENDENT KINASES, mitogen-activated kinases, CYCLINS, and phosphoprotein phosphatases (PHOSPHOPROTEIN PHOSPHATASE) as well as their putative substrates such as chromatin-associated proteins, cytoskeletal proteins, and transcription factors. NOTE: DNA-binding proteins; control cell division cycle
Cell Death
The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness and adaptability
Cell Differentiation
Progressive restriction of the developmental potential and increasing specialization of function which takes place during the development of the embryo and leads to the formation of specialized cells, tissues, and organs. Note: cell differentiation is a normal process in morphogenesis
Cell Nucleolus
Within most types of eukaryotic CELL NUCLEUS, a distinct region, not delimited by a membrane, in which some species of rRNA (RNA, RIBOSOMAL) are synthesized and assembled into ribonucleoprotein subunits of ribosomes. In the nucleolus rRNA is transcribed from a nucleolar organizer, i.e., a group of tandemly repeated chromosomal genes which encode rRNA and which are transcribed by RNA polymerase I. (Singleton & Sainsbury, Dictionary of Microbiology & Molecular Biology, 2d ed)
Cell nucleus
Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell many contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)
Cell Survival
The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability
Cell Transformation, neoplastic
Cell changes manifested by escape from control mechanisms, increased growth potential, alterations in the cell surface, karyotypic abnormalities, morphological and biochemical deviations from the norm, and other attributes conferring the ability to invade, metastasize, and kill. NOTE: do not confuse with CELL DIFFERENTIATION, a normal process in morphogenesis
Chaperonins
A class of sequence-related MOLECULAR CHAPERONES found in bacteria, mitochondria, and plastids. Chaperonins are abundant constitutive proteins that increase in amount after stresses such as heat shock, bacterial infection of macrophages, and an increase in the cellular content of unfolded proteins. Bacterial chaperonins are major immunogens in human bacterial infections because of their accumulation during the stress of infection. Two members of this class of chaperones are CHAPERONIN 10 and CHAPERONIN 60
Chloramphenicol Acetyltransferase
An enzyme that catalyzes the acetylation of chloramphenicol to yield chloramphenicol 3-acetate. Since chloramphenicol 3-acetate does not bind to bacterial ribosomes and is not an inhibitor of peptidyltransferase, the enzyme is responsible for the naturally occurring chloramphenicol resistance in bacteria. The enzyme, for which variants are known, is found in both gram-negative and gram-positive bacteria
Chorionic Gonadotropin, beta Subunit, Human
The beta subunit of human chorionic gonadotropin. It is used as a clinical marker to facilitate early detection of normal pregnancy and significantly contributes to the diagnosis of various pregnancy-related disorders, such as ectopic pregnancy, spontaneous abortion, hydatidiform mole, choriocarcinoma, or Trisomy 21. Further, determination of this marker is immensely helpful to guide curative intervention in testicular cancer. Other possible clinical uses includes as a marker of cancers of the bladder, pancreas, or biliary tract. (Scan J Clin Lab Invest Suppl 1993;216:97-104)
Chromogranins
Nerve tissue proteins
Chromosome Aberrations
Deviations from the normal number or structure of chromosomes, not necessarily associated with disease. Note: structural or numerical deviations not necessarily manifesting as disease or patent abnormality
Chromosome Abnormalities
Defects in the structure or number of chromosomes resulting in structural aberrations or manifesting as disease
Chromosome Deletion
Actual loss of a portion of the chromosome
Chromosomes, Human
The structures within the human cell nucleus that contain the hereditary material, DNA. There are 46 chromosomes: normally present in the human, including two which determine the sex of individual, XX for the female and XY for the male. Human chromosomes are classified into groups sharing structural similarity in terms of length from the centromere
Clathrin
The main structural coat protein of coated vesicles which play a key role in the intracellular transport between membranous organelles. Clathrin also interacts with cytoskeletal proteins. NOTE: a membrane protein
Coenzymes
Organic nonprotein molecules, frequently phosphorylated derivatives of water-soluble vitamins, that bind with the protein molecule (APOENZYMES) to form the active enzyme (holoenzyme). They are catalysts for the activation of enzymes. (Dorland, 28th ed; Grant & Hackh's Chemical Dictionary, 5th ed)
Collagenases
Enzymes that catalyze the degradation of collagen by acting on the peptide bonds
Cyclin-dependent kinases
Protein kinases that control cell cycle progression in all eukaryotes and require physical association with CYCLINS to achieve full enzymatic activity. Cyclin-dependent kinases are regulated by phosphorylation and dephosphorylation events
Cyclins
Regulatory proteins that function in the cell cycle to activate maturation promoting factor. They complex with p34cdc2 (protein p34cdc2), the catalytic subunit of maturation promoting factor, and modulate its protein kinase activity. Cyclins themselves have no enzymatic activity. Note: regulatory proteins; growth substances; do not confuse with the nuclear protein cyclin (PCNA or Proliferating Cell Nuclear Antigen)
Cytogenetics
A branch of genetics which deals with the cytological and molecular behavior of genes and chromosomes during cell division
Cytokines
Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner
Cytoskeletal Proteins
Major constituent of the cytoskeleton found in the cytoplasm of eukariotic cells. They form a flexible framework for the cell, provide attachment points for organelles and formed bodies, and make communication between parts of the cell possible

D

Diagnosis, Computer-Assisted
Application of computer programs designed to assist the physician in solving a diagnostic problem
Diagnosis, Laboratory
Diagnosis based on findings of laboratory tests
Diagnostic Tests, Routine
Diagnostic procedures, such as laboratory tests and x-rays, routinely performed on all individuals or specified categories of individuals in a specified situation, e.g., patients being admitted to the hospital. These include routine tests administered to neonates
Diploidy
The chromosomal constitution of somatic cells, in which each type of chromosome is represented twice. Symbol: 2N or 2X
DNA Damage
Drug- or radiation-induced injuries in DNA that introduce deviations from its normal double-helical conformation. These changes include structural distortions which interfere with replication and transcription, as well as point mutations which disrupt base pairs and exert damaging effects on future generations through changes in DNA sequence. If the damage is minor, it can often be repaired (DNA REPAIR). If the damage is extensive, it can induce apoptosis
DNA Fragmentation
Endonucleolytic cleavage of genomic DNA into oligonucleosomal fragments at internucleosomal sites. DNA fragmentation along with chromatin condensation are considered the hallmarks of APOPTOSIS. NOTE: cleavage of DNA into fragments at internucleosomal sites: do not confuse with DNA DAMAGE which is by drugs or radiation
DNA Methylation
Enzymatic addition of methyl groups to DNA. This is performed by DNA methyltransferases (DNA methylases) which all use S-Adenosylmethionine as the methyl group donor. Ancestrally a mechanism for neutralizing potentially damaging DNA elements in the prokaryote genome, in eukaryote vertebrates it appears to play a regulatory role in gene expression
DNA Modification Methylases
Enzymes that are part of the restriction-modification systems. They are responsible for producing a species-characteristic methylation pattern, on either adenine or cytosine residues, in a specific short base sequence in the host cell's own DNA. This methylated sequence will occur many times in the host-cell DNA and remain intact for the lifetime of the cell. Any DNA from another species which gains entry into a living cell and lacks the characteristic methylation pattern will be recognized by the restriction endonucleases of similar specificity and destroyed by cleavage. Most have been studied in bacterial systems, but a few have been found in eukaryotic organisms
DNA, neoplasm
DNA present in neoplastic tissue
DNA Repair
The reconstruction of a continuous two-stranded DNA molecule without mismatch from a molecule which contained damaged regions. The major repair mechanisms are excision repair, in which defective regions in one strand are excised and resynthesized using the complementary base pairing information in the intact strand; photoreactivation, in which the lethal and mutagenic effects of ultraviolet light are eliminated; and post-replication repair, in which the primary lesions are not repaired, but the gaps in one daughter duplex are filled in by incorporation of portions of the other (undamaged) daughter duplex. Excision repair and post-replication repair are sometimes referred to as "dark repair" because they do not require light
DNA Topoisomerase
An enzyme catalyzing ATP-independent breakage of single-stranded DNA, followed by passage and rejoining of another single-stranded DNA. This enzyme class brings about the conversion of one topological isomer of DNA into another, e.g., the relaxation of superhelical turns in DNA, the interconversion of simple and knotted rings of single-stranded DNA, and the intertwisting of single-stranded rings of complementary sequences. (From Enzyme Nomenclature, 1992)
DNA-binding Proteins
Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases
DNA-binding proteins
Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases
Down-Regulation (Physiology)
Process that decreases ligand/receptor interactions due to a reduction in the number of available receptors. This can result from internalization of the ligand/receptor complex or from decreased expression of the receptor. Classically the concept referred to hormone receptors but contemporary usage includes other cell surface receptors. NOTE: "regulation" refers to ligand/receptor interactions
Drug Resistance
Diminished or failed response of a human, animal, disease, or tissue to the intended effectiveness of a chemical or drug. It does not include the resistance of micro-organisms to drugs for which DRUG RESISTANCE, MICROBIAL is available. It should be differentiated from DRUG TOLERANCE which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration
Drug Resistance, Multiple
Simultaneous resistance to a broad spectrum of structurally and functionally distinct drugs following exposure to a single agent. It is thought to result from the overexpression of genes encoding an integral plasma membrane protein, P-GLYCOPROTEIN.
Drug Resistance, Neoplasm
Resistance or diminished response of a neoplasm to an antineoplastic agent in humans, animals, or cell or tissue cultures

E

Endothelial growth factors
These growth factors are soluble mitogens secreted by a variety of organs. The factors are a mixture of two single chain polypeptides which have affinity to heparin. Their molecular weight are organ and species dependent. They have mitogenic and chemotactic effects and can stimulate endothelial cells to grow and synthesize DNA. The factors are related to both the basic and acidic fibroblast growth factors but have different amino acid sequences
Enzyme activation
Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1) activation by ions (activators); 2) activation by cofactors (coenzymes); and 3) conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme
Enzyme inhibitors
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction
Epidermal Growth Factor Receptor Protein-Tyrosine Kinase
The catalytic PROTEIN-TYROSINE KINASE domain found on the cytoplasmic beta-portion of epidermal growth factor receptor
Epidermal Growth Factor-Urogastrone
Single chain, non helical, acidic polypeptides of about 52 amino acids found in most mammels. Epidermal growth factor and urogastrone are not identical but seem to share biological activities. They promote growth of, and cell proliferation in, certain tissues, especially epidermal structures and inhibit acid secretion by the stomach. They have been used to treat gastrointestinal ulcers
Evidence-Based Medicine
The process of systematically finding, appraising, and using contemporaneous research findings as the basis for clinical decisions. Evidence-based medicine asks questions, finds and appraises the relevant data, and harnesses that information for everyday clinical practice. Evidence-based medicine follows four steps: formulate a clear clinical question from a patient's problem; search the literature for relevant clinical articles; evaluate (critically appraise) the evidence for its validity and usefulness; implement useful findings in clinical practice. The term "evidence based medicine" (no hyphen) was coined at McMaster Medical School in Canada in the 1980's to label this clinical learning strategy, which people at the school had been developing for over a decade. (From BMJ 1995;310:1122)

F

Fibroblast Growth Factor
Peptide isolated from the pituitary gland and from the brain. It is a potent mitogen which stimulates growth of a variety of mesodermal cells including chondrocytes, granulosa, and endothelial cells. The peptide may be active in wound healing and animal limb regeneration
Fibroblast Growth Factor, acidic
A growth factor which has been isolated from a variety of cells. It contains 154 amino acid residues and has potent heparin-binding activity. Heparin potentiates the biological activities of aFGF. The growth factor is an extremely potent inducer of DNA synthesis in a variety of normal diploid mammalian cell types from mesoderm and neuroectoderm lineages and also has chemotactic and mitogenic activities
Fibroblast Growth Factor, basic
A single-chain polypeptide of approximately 15-16 kDa which has been isolated from a variety of cells. It has a 55% amino acid residue identity to acidic fibroblast growth factor and has potent heparin-binding activity. However, in contrast to the acidic fibroblast growth factor, heparin does not potentiate the biological activities of bFGF. The growth factor is an extremely potent inducer of DNA synthesis in a variety of normal diploid mammalian cell types from mesoderm and neuroectoderm lineages and promotes cellular differentiation in vitro
Frameshift Mutation
A type of mutation in which a number of nucleotides not divisible by three is deleted from or inserted into a coding sequence, thereby causing an alteration in the reading frame of the entire sequence downstream of the mutation. These mutations may be induced by certain types of mutagens or may occur spontaneously. NOTE: non-physiol insertion or deletion of coding sequence nucleotides; do not confuse with FRAMESHIFTING, RIBOSOMAL, physiol process & form of genet translation; do not confuse eff of drug & radiation on frameshift mutation with drug- & radiation-induced frame mutation

G

G-Proteins
The mediators of activated cell-surface receptors and their enzymes or of ion channels. They are responsible for activating a chain of events that alters the concentration of intracellular signaling molecules (i.e., intracellular messengers) such as cyclic AMP and Ca2+. In turn, these intracellular messengers alter the behavior of other target proteins within the cell. Note: membrane proteins
Galactosyltransferases
Enzymes that catalyze the transfer of galactose from a nucleoside diphosphate galactose to an acceptor molecule which is frequently another carbohydrate
Gamma-glutamyltransferase
An enzyme that catalyzes reversibly the transfer of a glutamyl group from a glutamyl-peptide and an amino acid to a peptide and a glutamyl-amino acid
Gelatinases
A class of enzymes that catalyzes the degradation of gelatin by acting on the peptide bonds
Gene Amplification
A selective increase in the number of copies of a gene coding for a specific protein without a proportional increase in other genes. It occurs naturally via the excision of a copy of the repeating sequence from the chromosome and its extrachromosomal replication in a plasmid, or via the production of an RNA transcript of the entire repeating sequence of ribosomal RNA followed by the reverse transcription of the molecule to produce an additional copy of the original DNA sequence. Laboratory techniques have been introduced for inducing disproportional replication by unequal crossing over, uptake of DNA from lysed cells, or generation of extrachromosomal sequences from rolling circle replication
Gene Deletion
A genetic rearrangement trough loss of segments of DNA or RNA, bringing sequences which are normally separated into close proximity. This deletion may be detected using cytogenetic techniques and can also be inferred from the phenotype, indicating a deletion at one specific locus
Gene Expression
The phenotypic manifestation of a gene or genes by the processes of gene action
Gene Expression Regulation
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action at the level of transcription or translation. These processes include gene activation and genetic induction
Gene Expression Regulation, Neoplastic
Any of the processes by which nuclear, cytoplasmic, or intracellular factors influence the differential control of gene action in neoplastic tissue
Gene Rearrangement
Ordered rearrangement of variable gene regions; especially, the rearrangement of antibody genes during the differentiation of B-lymphocytes and the rearrangement of T-cell antigen receptor genes
Genes
Specific sequences of nucleotides along a molecule of DNA (or, in the case of some viruses, RNA) which represent the functional units of heredity. The majority of eukaryotic genes contain coding regions (codons) that are interrupted by non-coding regions (introns) and are therefore labeled split genes
Genes, abl
Retrovirus-associated DNA sequences (abl) originally isolated from the Abelson murine leukemia virus (Ab-MuLV). The proto-oncogene abl (c-abl) codes for a protein that is a member of the tyrosine kinase family. The human c-abl gene is located at 9q34.1 on the long arm of chromosome 9. It is activated by translocation to bcr on chromosome 22 in chronic myelogenous leukemia. NOTE: abl stands for "ABelson Leukemia"
Genes, bcl-2
The B-cell leukemia/lymphoma-2 genes, responsible for blocking apoptosis in normal cells, and associated with follicular lymphoma when overexpressed. Overexpression results from the t(14;18) translocation. The human c-bcl-2 gene is located at 18q24 on the long arm of chromosome 18. NOTE: bcl stands for "B-Cell Leukemia"
Genes, BRCA1
Tumor suppressor genes located on human chromosome 17q12-21. The mutation of these genes is associated with the formation of familial breast and ovarian cancer.
Genes, DCC
Tumor suppressor genes located in the 18q21-qter region of human chromosome 18. The absence of these genes is associated with the formation of colorectal cancer (DCC stands for deleted in colorectal cancer). The products of these genes show significant homology to neural cell adhesion molecules and other related cell surface glycoproteins. NOTE: DCC stands for "Deleted in Colorectal Cancer"
Genes, erbA
Retrovirus-associated DNA sequences (ERYTHROBLASTOSIS VIRUS, AVIAN, hence erbA) originally isolated from the avian erythroblastosis virus. The c-erbA proto-oncogene encodes the thyroid hormone receptors (RECEPTORS, THYROID HORMONE). Two distinct c-erbA proto-oncogenes have been identified, erbA-alpha and erbA-beta, each giving rise to at least two proteins. erbA-alpha is located at 17q21 on the long arm of chromosome 17. erbA-beta is located at 3p24 on the short arm of chromosome 3. The v-erbA oncogene potentiates cell transformation through inhibition of spontaneous differentiation of cells already transformed by the v-erbB gene and eliminates growth requirements of transformed erythroblasts. NOTE: erbA stands for "ERythroBlastosis virus, Avian"
Genes, erbB
Retrovirus-associated DNA sequences (erbB) originally isolated from, or related to, the avian erythroblastosis virus (AEV). These genes code for the epidermal growth factor receptor (EGFR) family of receptors which is important in the control of normal cell proliferation and in the pathogenesis of human cancer. The genes include erbB-1 (GENES, ERBB-1), erbB-2 (GENES, ERBB-2), and erbB-3, all of which show abnormalities of expression in various human neoplasms
Genes, erbB-1
Retrovirus-associated DNA sequences (erbB) originally isolated from the avian erythroblastosis virus (AEV). The oncogene v-erbB arose by insertion of viral DNA into the c-erbB-1 proto-oncogene resulting in expression of a protein lacking the amino-terminal ligand-binding domain. v-erbB is the primary transforming gene of AEV and abrogates the requirements for other mitogens. The proto-oncogene c-erbB-1 codes for the protein epidermal growth factor receptor (EPIDERMAL GROWTH FACTOR RECEPTOR-UROGASTRONE). Overexpression of the gene occurs in a wide range of tumors, commonly squamous carcinomas of various sites and less commonly adenocarcinomas. The human c-erbB-1 gene is located at 7p12-13 on the short arm of chromosome 7
Genes, erbB-2
Retrovirus-associated DNA sequences (erbB) related to the c-erbB-1 gene and identified by probes from c-erbB-1 or its avian viral homologue v-erbB. The proto-oncogene erbB-2 (c-erbB-2) codes for a protein that has structural features indicative of a growth factor receptor with close similarity to the epidermal growth factor (EGF) receptor. Overexpression and amplification of the gene is associated with adenocarcinomas and with poor prognosis in breast carcinomas. The human c-erbB-2 gene is located at 17p12-21 on the short arm of chromosome 17
Genes, fms
Family of retrovirus-associated DNA sequences (fms) originally isolated from the Susan McDonough strain of feline sarcoma virus (SM-FeSV). The proto-oncogene fms (c-fms) codes for a protein (CSF-1) that is a member of the transmembrane tyrosine kinase growth factor receptor family. The human c-fms gene is located at 5q33.3 on the long arm of chromosome 5. NOTE: fms stands for "Feline McDonough Sarcoma", a family of DNA sequences "originally isolated from the Susan McDonough strain of feline sarcoma virus"
Genes, fos
Retrovirus-associated DNA sequences (fos) originally isolated from the Finkel-Biskis-Jinkins (FBJ-MSV) and Finkel-Biskis-Reilly (FBR-MSV) murine sarcoma viruses. The proto-oncogene protein c-fos codes for a nuclear protein which is involved in growth-related transcriptional control. The insertion of c-fos into FBJ-MSV or FBR-MSV induces osteogenic sarcomas in mice. The human c-fos gene is located at 14q21-31 on the long arm of chromosome 14. NOTE: fos stands for "Finkel" & "Osteogenic Sarcoma"
Genes, Intracisternal A-Particle
A family of retrovirus-like genetic elements coding for virus-like particles found regularly in early rodent embryos but which, under certain circumstances such as DNA hypomethylation, are transcribed in a wide variety of neoplasms, including plasmacytomas, neuroblastomas, rhabdomyosarcomas, teratocarcinomas, and colon carcinomas. NOTE: "intracisternal" refers to the cisternae of the endoplasmic reticulum
Genes, jun
Retrovirus-associated DNA sequences (jun) originally isolated from the avian sarcoma virus 17 (ASV 17). The proto-oncogene jun (c-jun) codes for a nuclear protein which is involved in growth-related transcriptional control. Insertion of c-jun into ASV-17 or the constitutive expression of the c-jun protein produces tumorgenicity. The human c-jun gene is located at 1p31-32 on the short arm of chromosome 1. NOTE: jun stands for "JU-Nana", Japanese for 17 (avian sarcoma virus 17)
Genes, MDR
Genes responsible for multidrug resistance resulting from their overexpression in mammalian cells. Mammalian P-glycoproteins are encoded by small MDR gene familes. The human multidrug resistance 1 (MDR1) gene responds to environmental stress including various anticancer agents. It is a major determinant in the development of resistance to a large number of cancer chemotherapeutic agents. (Biochem Biophys Res Commun 1994;199(3):1428-35; Cancer Res 1994:54(6):1536-41). NOTE: MDR stands for 'MultiDrug Resistance'
Genes, mos
Retrovirus-associated DNA sequences (mos) originally isolated from the Moloney murine sarcoma virus (Mo-MSV). The proto-oncogene mos (c-mos) codes for a protein which is a member of the serine kinase family. There is no evidence as yet that human c-mos can become transformed or has a role in human cancer. However, in mice, activation can occur when the retrovirus-like intracisternal A-particle inserts itself near the c-mos sequence. The human c-mos gene is located at 8q22 on the long arm of chromosome 8. NOTE: mos stands for "MOloney Sarcoma"
Genes, myc
Family of retrovirus-associated DNA sequences (myc) originally isolated from an avian myelocytomatosis virus. The proto-oncogene myc (c-myc) codes for a nuclear protein which is involved in nucleic acid metabolism and in mediating the cellular response to growth factors. Truncation of the first exon, which appears to regulate c-myc expression, is crucial for tumorigenicity. The human c-myc gene is located at 8q24 on the long arm of chromosome 8. NOTE: myc stands for "MYeloCytomatosis"
Genes, p53
Tumor suppressor genes located on the short arm of human chromosome 17 and coding for the phosphoprotein p53
Genes, ras
Family of retrovirus-associated DNA sequences (ras) originally isolated from Harvey (H-ras, Ha-ras, rasH) and Kirsten (K-ras, Ki-ras, rasK) murine sarcoma viruses. Ras genes are widely conserved among animal species and sequences corresponding to both H-ras and K-ras genes have been detected in human, avian, murine, and non-vertebrate genomes. The closely related N-ras gene has been detected in human neuroblastoma and sarcoma cell lines. All genes of the family have a similar exon-intron structure and each encodes a p21 protein. NOTE: ras stands for "Retrovirus Associated Sequences"
Genes, Retinoblastoma
Tumor suppressor genes located on human chromosome 13 in the region 13q14 and coding for a family of phosphoproteins with molecular weights ranging from 104 kDa to 115 kDa. One copy of the wild-type Rb gene is necessary for normal retinal development. Loss or inactivation of both alleles at this locus results in retinoblastoma
Genes, src
Retrovirus-associated DNA sequences (src) originally isolated from the Rous sarcoma virus (RSV). The proto-oncogene src (c-src) codes for a protein that is a member of the tyrosine kinase family and was the first proto-oncogene identified in the human genome. The human c-src gene is located at 20q12-13 on the long arm of chromosome 20. NOTE: src stands for "SaRComa"
Genes, Suppressor
Genes that inhibit expression of a previous mutation. They allow the wild-type phenotype to be wholly or partially restored
Genes, Suppressor, Tumor
Genes that inhibit expression of the tumorigenic phenotype. They are normally involved in holding cellular growth in check. When tumor suppressor genes are inactivated or lost, a barrier to normal proliferation is removed and deregulated growth is possible
Genetic Markers
A phenotypically recognizable genetic trait which can be used to identify a genetic locus, a linkage group, or a recombination event
Glucuronosyltransferase
A family of enzymes accepting a wide range of substrates, including phenols, alcohols, amines, and fatty acids. They function as drug-metabolizing enzymes that catalyze the glucuronic acid conjugation of a variety of endogenous and exogenous compounds
Glutathione Peroxidase
An enzyme catalyzing the oxidation of 2 moles of glutathione in the presence of hydrogen peroxide to yield oxidized glutathione and water. CAS TYPE 1 NAME: Glutathione:hydrogen-peroxide oxidoreductase
Glutathione transferases
Transferases that catalyze the addition of aliphatic, aromatic, or heterocyclic radicals as well as epoxides and arene oxides to glutathione. Addition takes place at the sulfur atom. They also catalyze the reduction of polyol nitrate by glutathione to polyol and nitrite. CAS TYPE 1 NAME: RX:glutathione R-transferase
Glyceraldehydephosphate dehydrogenase
D-Glyceraldehyde-3-phosphate:NADP+ oxidoreductase
Gonadorelin
Luteinizing hormone-releasing factor. A decapeptide hormone released by the hypothalamus that stimulates the secretion of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the pituitary gland. NOTE: a neurotransmitter hypothalamic hormone
Goserelin
6-(O-(1,1-Dimethylethyl)-D-serine)-10-deglycinamideluteinizing hormone-releasing factor (pig) 2-(aminocarbonyl)hydrazide. A long-acting GONADORELIN agonist. It is used in the treatment of malignant neoplasms of the prostate, uterine fibromas, and metastatic breast cancer. NOTE: a hormonal antineoplastic. PHARMACOLOGIC ACTION: Antineoplastic Agents, Hormonal
Growth Inhibitors
Endogenous or exogenous substances which inhibit the normal growth of human and animal cells or micro-organisms, as distinguished from those affecting plant growth (= PLANT GROWTH REGULATORS)
Growth Substances
Signal molecules that are involved in the control of cell growth and differentiation
Guanylate Cyclase
An enzyme that catalyzes the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. It also acts on ITP and dGTP. (From Enzyme Nomenclature, 1992)

H

Haploidy
The number of chromosomes in the gametes, which is half the number normally found in somatic cells. Symbol: N.
Haplotypes
The genetic constitution of individuals with respect to one member of a pair of allelic genes; sets of single alleles or closely linked genes that tend to be inherited together, such as those of the major histocompatibility complex; portions of phenotypes determined by genes located on one of a pair of chromosomes
Heat Shock Proteins
Proteins which are synthesized in eukaryotic organisms and bacteria in response to hyperthermia and other environmental stresses. They increase thermal tolerance and perform functions essential to cell survival under these conditions
Heat-Shock Protein 27
Proteins which are synthesized in eukaryotic organisms and bacteria in response to hyperthermia and other environmental stresses. They increase thermal tolerance and perform functions essential to cell survival under these conditions
Heat-Shock Proteins
Proteins which are synthesized in eukaryotic organisms and bacteria in response to hyperthermia and other environmental stresses. They increase thermal tolerance and perform functions essential to cell survival under these conditions
Heat-Shock Proteins 70
A class of molecular chaperones found in both prokariotes and in several compartments of eukariotic cells. There is evidence that these proteins can interact with polypeptides during a variety of assembly processes in such a way as to prevent the formation of nonfunctional structures
Heat-Shock Proteins 90
A class of molecular chaperones whose members act in the mechanism of signal transduction by steroid receptors
Hepatocyte Growth Factor
Multifunctional growth factor which regulates both cell growth and cell motility. It exerts a strong mitogenic effect on hepatocytes and primary epithelial cells. Its receptor is the proto-oncogene protein c-met.
High Mobility Group Proteins
A group of non-histone proteins found in chromatin. Their role has not been definitely established, but they are believed to have a role in matrix stabilization, protection of single-stranded DNA, and are required for transcription
Hormones
Chemical substances having a specific regulatory effect on the activity of a certain organ or organs. The term was originally applied to substances secreted by various endocrine glands and transported in the bloodstream to the target organs. It is sometimes extended to include those substances that are not produced by the endocrine glands but that have similar effects
Hormones, Ectopic
Hormones released from neoplasms or cells outside the usual sources of hormones. Such hormones may be useful as tumor markers. (Dorland, 28th ed)

I

Image Cytometry
A technique encompassing morphometry, densitometry, neural networks, and expert systems that has numerous clinical and research applications and is particularly useful in anatomic pathology for the study of malignant lesions. The most common current application of image cytometry is for DNA analysis, followed by quantitation of immunohistochemical staining. NOTE: a cytophotometry technique
Insulin-Like Growth Factor I
A well-characterized basic peptide believed to be secreted by the liver and to circulate in the blood. It has growth-regulating, insulin-like, and mitogenic activities. This growth factor has a major, but not absolute, dependence on SOMATOTROPIN. It is believed to be mainly active in adults in contrast to INSULIN-LIKE GROWTH FACTOR II, which is a major fetal growth factor. NOTE: a neurotransmitter somatomedin
Insulin-Like Growth Factor II
A well-characterized neutral peptide believed to be secreted by the liver and to circulate in the blood. It has growth-regulating, insulin-like and mitogenic activities. The growth factor has a major, but not absolute, dependence on SOMATOTROPIN. It is believed to be a major fetal growth factor in contrast to INSULIN-LIKE GROWTH FACTOR I, which is a major growth factor in adults. NOTE: a neurotransmitter somatomedin
Insulin-Like Growth Factor-Binding Protein 1
One of the six homologous proteins that specifically bind insulin-like growth factors (SOMATOMEDINS) and modulate their mitogenic and metabolic actions. The function of this protein is not completely defined. However, several studies demonstrate that it inhibits IGF binding to cell surface receptors and thereby inhibits IGF-mediated mitogenic and cell metabolic actions. (Proc Soc Exp Biol Med 1993;204(1):4-29)
Insulin-Like Growth Factor-Binding Protein 2 to 6
One of the six homologous soluble proteins that bind insulin-like growth factors (SOMATOMEDINS) and modulate their mitogenic and metabolic actions at the cellular level
Insulin-Like Growth-Factor-Binding Proteins
A family of soluble proteins that bind insulin-like growth factors and modulate their biological actions at the cellular level. (Int J Gynaecol Obstet 1992;39(1):3-9)
Integrins
A family of transmembrane glycoproteins consisting of noncovalent heterodimers. They interact with a wide variety of ligands including extracellular matrix glycoproteins, complement, and other cells, while their intracellular domains interact with the cytoskeleton. The integrins consist of at least three identified families: the cytoadhesin receptors, the leukocyte adhesion receptors, and the very-late-antigen receptors. Each family contains a common beta-subunit combined with one or more distinct alpha-subunits. These receptors participate in cell-matrix and cell-cell adhesion in many physiologically important processes, including embryological development, hemostasis, thrombosis, wound healing, immune and nonimmune defense mechanisms, and oncogenic transformation. NOTE: a family of glycoproteins acting as immunologic receptors
Intercellular Adhesion Molecule-1
A cell-surface ligand with a role in leukocyte adhesion and inflammation. Its production is induced by gamma-interferon and it is required for neutrophil migration into inflamed tissue
Interferon Type II
The major interferon produced by mitogenically or antigenically stimulated lymphocytes. It is structurally different from type I interferon (INTERFERON TYPE I) and its major activity is immunoregulation. It has been implicated in the expression of class II histocompatibility antigens in cells that do not normally produce them, leading to autoimmune disease. CAS TYPE 1 NAME: Interferon gamma (human lymphocyte protein moiety reduced) PHARMACOLOGIC ACTION: Antineoplastic Agents; Antiviral Agents.
Interferon-alpha
One of the type I interferons (INTERFERON TYPE I) produced by peripheral blood leukocytes or lymphoblastoid cells when exposed to live or inactivated virus, double-stranded RNA, or bacterial products. It is the major interferon produced by virus-induced leukocyte cultures and, in addition to its pronounced antiviral activity, causes activation of NK cells. It is used experimentally in the treatment of hairy-cell leukemia. PHARMACOLOGIC ACTION: Antineoplastic Agents; Antiviral Agents
Interferons
Proteins secreted by vertebrate cells in response to a wide variety of inducers. They confer resistance against many different viruses, inhibit proliferation of normal and malignant cells, impede multiplication of intracellular parasites, enhance macrophage and granulocyte phagocytosis, augment natural killer cell activity, and show several other immunomodulatory functions. NOTE: antiviral & antineoplastic agents, do not confuse with VIRUS INHIBITORS, substances found in normal serum, body fluids or tissue. PHARMACOLOGIC ACTION: Antineoplastic Agents; Antiviral Agents
Interleukin-2
Soluble substances elaborated by antigen- or mitogen-stimulated T-lymphocytes which induce DNA synthesis in naive lymphocytes.
Interleukin-6
Factor that stimulates the growth and differentiation of human B-cells and is also a growth factor for hybridomas and plasmacytomas. It is produced by many different cells including T-cells, monocytes, and fibroblasts.
Interleukin-8
A cytokine that activates neutrophils and attracts neutrophils and T-lymphocytes. It is released by several cell types including monocytes, macrophages, T-lymphocytes, fibroblasts, endothelial cells, and keratinocytes by an inflammatory stimulus. IL-8 is a member of the beta-thromboglobulin superfamily and structurally related to platelet factor 4.
Interleukins
Soluble factors which stimulate growth-related activities of leukocytes as well as other cell types. They enhance cell proliferation and differentiation, DNA synthesis, secretion of other biologically active molecules and responses to immune and inflammatory stimuli.

J

K

Kallikrein
Peptidohydrolytic enzyme found in normal blood and urine. It is involved in blood coagulation and is formed from prekallikrein, probably by clotting factor XII. Kallikrein is a potent vasodilator and hypotensive, increases vascular permeability and affects smooth muscle. It is thereby intimately involved in inflammation and allergic reactions. Two forms are recognized, plasma kallikrein (EC 3.4.21.34) and tissue kallikrein (EC 3.4.21.35). NOTE: a blood coag factor; a serine proteinase; /antag permitted but consider KALLIKREIN-TRYPSIN INACTIVATOR
Keratin
A class of fibrous proteins or scleroproteins important both as structural proteins and as keys to the study of protein conformation. The family represents the principal constituent of epidermis, hair, nails, horny tissues, and the organic matrix of tooth enamel. Two major conformational groups have been characterized, alpha-keratin, whose peptide backbone forms an alpha-helix, and beta-keratin, whose backbone forms a zigzag or pleated sheet structure
Ki-67 Antigen
A cell cycle and tumor growth marker which can be readily detected using immunocytochemistry methods. Ki-67 is a nuclear antigen present only in the nuclei of cycling cells

L

Laminin
Large, noncollagenous glycoprotein with antigenic properties. It is localized in the basement membrane lamina lucida and functions to bind epithelial cells to the basement membrane. Evidence suggests that the protein plays a role in tumor invasion. NOTE: an extracellular matrix protein
LH
A small glycoprotein hormone secreted by the anterior pituitary. LH plays an important role in controlling ovulation and in controlling secretion of hormones by the ovaries and testes. NOTE: a neurotransmitter pituitary hormone; Luteinizing Hormone
Linkage (Genetics)
The association in inheritance of two or more non-allelic genes due to their being located more or less closely on the same chromosome
Lymphokines
Soluble protein factors generated by activated lymphocytes that affect other cells, primarily those involved in cellular immunity

M

Macrophage Migration-Inhibitory Factors
Proteins released by sensitized lymphocytes and possibly other cells that inhibit the migration of macrophages away from the release site. The structure and chemical properties may vary with the species and type of releasing cell. NOTE: a lymphokine
Mass Screening
Organized periodic procedures performed on large groups of people for the purpose of detecting disease
Maturation-promoting factor
Protein kinase that drives both the mitotic and meiotic cycles in all eukaryotic organisms. In meiosis it induces immature oocytes to undergo meiotic maturation. In mitosis it has a role in the G2/M phase transition. Once activated by CYCLINS, MPF directly phosphorylates some of the proteins involved in nuclear envelope breakdown, chromosome condensation, spindle assembly, and the degradation of cyclins. The catalytic subunit of MPF is PROTEIN P34CDC2. NOTE: a protein kinase
Membrane Glycoproteins
Glycoproteins found on the membrane or surface of cells
Membrane metallo-endopeptidase
Term has been mapped to 'Neprilysin'..... MeSH HEADING: NEPRILYSIN. SCOPE: Enzyme that is a major constituent of kidney brush-border membranes and is also present to a lesser degree in the brain and other tissues. It preferentially catalyzes cleavage at the amino group of hydrophobic residues of the B-chain of insulin as well as opioid peptides and other biologically active peptides. The enzyme is inhibited primarily by EDTA, phosphoramidon, and thiorphan and is reactivated by zinc. Neprilysin is identical to common acute lymphoblastic leukemia antigen (CALLA), an important marker in the diagnosis of human acute lymphocytic leukemia. NOTE: identical to Common Acute Lymphoblastic Leukemia Antigen (CALLA)
Membrane Proteins
Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors
Membrane Proteins
Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors
Meta-analysis
A quantitative method of combining the results of independent studies (usually drawn from the published literature) and synthesizing summaries and conclusions which may be used to evaluate therapeutic effectiveness, plan new studies, etc., with application chiefly in the areas of research and medicine
Metalloproteinases
Peptide hydrolases which use a metal in the catalytic mechanism. This group of enzymes is inactivated by metal chelators
Methylation
Addition of methyl groups. In histo-chemistry methylation is used to esterify carboxyl groups and remove sulfate groups by treating tissue sections with hot methanol in the presence of hydrochloric acid. (From Stedman, 25th ed)
Microcirculation
The vascular network lying between the arterioles and venules; includes capillaries, metarterioles and arteriovenous anastomoses. Also, the flow of blood through this network
Microfilament Proteins
Filaments which are composed primarily of actin and found in the cytoplasmic matrix of almost all cells. They are often associated with microtubules and may play a role in cytoskeletal function and/or mediate movement of the cell or the organelles within the cell
Microsatellite repeats
A variety of simple di- (DINUCLEOTIDE REPEATS), tri- (TRINUCLEOTIDE REPEATS), tetra-, and pentanucleotide tandem repeats that are dispersed in the euchromatic arms of most chromosomes. The dinucleotide repeat of guanine and thymine, (GT)n, is the most common of these dispersed repeats. (From Cooper, The Human Genome Project, 1994, p186)
Mitosis
A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species
Mitotic Index
An expression of the number of mitoses found in a stated number of cells
Monokines
Soluble mediators of the immune response that are neither antibodies nor complement. They are produced largely, but not exclusively, by monocytes and macrophages
Monophenol Monooxygenase
An enzyme of the oxidoreductase class that catalyzes the reaction between L-tyrosine, L-dopa, and oxygen to yield L-dopa, dopaquinone, and water. It is a copper protein that acts also on catechols, catalyzing some of the same reactions as CATECHOL OXIDASE
MSH
Peptide hormones secreted by the intermediate lobe of the pituitary that stimulate melanin release and dispersal. Melanocyte-stimulating hormones are also found in the brain where they are presumed to play a signaling role. NOTE: neurotransmitter pituitary hormones; Melanotropin
Mucins
A secretion containing mucopolysaccharides and protein that is the chief constituent of mucus
Mutagenesis
Process of generating genetic mutations. It may occur spontaneously or be induced by mutagens
Mutagenesis, Insertional
Mutagenesis where the mutation is caused by the introduction of foreign DNA sequences into a gene. This may occur spontaneously in vivo or be experimentally induced in vivo or in vitro. Proviral DNA can be inserted into or adjacent to a cellular proto-oncogene. Insertion of the provirus can cause mutations by interrupting coding sequences or regulatory elements, or cause unregulated expression of the proto-oncogene resulting in tumor formation.
Mutation
Any detectable and heritable change in the genetic material not caused by genetic segregation or recombination, which is transmitted to daughter cells and to succeeding generations, providing it is not a dominant lethal factor

N

Neoplasm circulating cells
Exfoliate neoplastic cells circulating in the blood and associated with metastasizing tumors
Neoplasm Staging
Methods which attempt to express in replicable terms the extent of the neoplasm in the patient
Neoplasms, Hormone-Dependent
Certain tumors that 1) arise in organs that are normally dependent on specific hormones and 2) are stimulated or caused to regress by manipulation of the endocrine environment
Neovascularization, Pathologic
Proliferation of blood vessels in tissue not normally containing them, or proliferation of blood vessels of a different kind than usual in tissue. It includes angiogenesis in tumor growth, diabetic retinopathy, hemangiomas, arthritis, and psoriasis. (Stedman, 25th ed & Segen, Dictionary of Modern Medicine, 1992). NOTE: a pathol process; do not confuse with NEOVASCULARIZATION, PHYSIOLOGIC, a physiol phenomenon
Neprilysin
Enzyme that is a major constituent of kidney brush-border membranes and is also present to a lesser degree in the brain and other tissues. It preferentially catalyzes cleavage at the amino group of hydrophobic residues of the B-chain of insulin as well as opioid peptides and other biologically active peptides. The enzyme is inhibited primarily by EDTA, phosphoramidon, and thiorphan and is reactivated by zinc. Neprilysin is identical to common acute lymphoblastic leukemia antigen (CALLA), an important marker in the diagnosis of human acute lymphocytic leukemia
Nerve Growth Factors
Factors which enhance the growth potentialities of sensory and sympathetic nerve cells
Nerve Tissue Protein S 100
Highly acidic calcium-binding protein found in large concentration in the brain and believed to be glial in origin; also found in other organs in the body
Neuropeptide Y
A 36-amino acid peptide present in many organs and in many sympathetic noradrenergic neurons. It has vasoconstrictor and natriuretic activity and regulates local blood flow, glandular secretion, and smooth muscle activity. The peptide also stimulates feeding and drinking behavior and influences secretion of pituitary hormones. NOTE: a neurotransmitter. PHARMACOLOGIC ACTION: Appetite Stimulants
Neuropeptides
Peptides released by neurons as intercellular messengers. Many neuropeptides are also hormones released by non-neuronal cells. NOTE: neurotransmitters
Neurotensin
A biologically active tridecapeptide isolated from the hypothalamus. It has been shown to induce hypotension in the rat, to stimulate contraction of guinea pig ileum and rat uterus, and to cause relaxation of rat duodenum. There is also evidence that it acts as both a peripheral and a central nervous system neurotransmitter. NOTE: a neurotransmitter isolated from the hypothalamus
NF-kappa B
Ubiquitous, inducible, nuclear transcriptional activator that binds to enhancer elements in lymphoid cells. In B-lymphocytes NF-kappa B binds to the immunoglobulin kappa light chain enhancer and in T-lymphocytes it has been shown to bind to the enhancers in virally infected cells including HIV
Nitric-oxide Synthase
An enzyme that catalyzes the conversion of L-arginine, NADPH, and oxygen to citrulline, nitric oxide, and NADP+. The enzyme found in brain, but not that induced in lung or liver by endotoxin, requires calcium. (From Enzyme Nomenclature, 1992)
Nuclear Proteins
Proteins found in the nucleus of a cell. Do not confuse with nucleoproteins which are proteins conjugated with nucleic acids, that are not necesseraly present in the nucleus. Note: proteins in the cell nucleus

O

Oncogene protein p21 (ras)
Transforming protein encoded by ras oncogenes. Point mutations in the cellular ras gene (c-ras) can also result in a mutant p21 protein that can transform mammalian cells. Oncogene protein p21(ras) has been directly implicated in human neoplasms, perhaps accounting for as much as 15-20% of all human tumors
Oncogene protein p55 (v-myc)
Transforming protein coded by myc oncogenes. The v-myc protein has been found in several replication-defective avian retrovirus isolates which induce a broad spectrum of malignancies
Oncogene proteins
Proteins coded by oncogenes. They include proteins resulting from the fusion of an oncogene and another gene (ONCOGENE PROTEINS, FUSION)
Oncogenes
Genes which can potentially induce neoplastic transformation. They include genes for growth factors, growth factor receptors, protein kinases, signal transducers, nuclear phosphoproteins, and transcription factors. When these genes are constitutively expressed after structural and/or regulatory changes, uncontrolled cell proliferation may result. Viral oncogenes have names of the form v-onc; cellular oncogenes (PROTO-ONCOGENES) are designated c-onc. NOTE: ONCOGENES cause neopl transform of cells
Orosomucoid
An alpha-globulin. Used For: alpha 1-acid glycoprotein (acute phase)
Osteocalcin
Vitamin K-dependent calcium-binding protein synthesized by osteoblasts and found primarily in bone. Serum osteocalcin measurements provide a noninvasive specific marker of bone metabolism. The protein contains three residues of the amino acid gamma-carboxyglutamic acid (Gla), which, in the presence of calcium, promotes binding to hydroxyapatite and subsequent accumulation in bone matrix
Oxidoreductases
The class of all enzymes catalyzing oxidoreduction reactions. The substrate that is oxidized is regarded as a hydrogen donor. The systematic name is based on donor: acceptor oxidoreductase. The recommended name will be dehydrogenase, wherever this is possible; as an alternative, reductase can be used. Oxidase is only used in cases where O2 is the acceptor. (Enzyme Nomenclature, 1992, p9)

P

P-Glycoprotein
Family of integral plasma membrane proteins which, when overexpressed, function as adenosine triphosphate-dependent efflux pumps, causing multidrug resistance (DRUG RESISTANCE, MULTIPLE). Mammalian P-glycoproteins are encoded by small mdr gene families. There are several isotypes in multiple species. NOTE: a carrier protein causing multidrug resist; P stands for "permeability"
P-Glycoprotein
Family of integral plasma membrane proteins which, when overexpressed, function as adenosine triphosphate-dependent efflux pumps, causing multidrug resistance (DRUG RESISTANCE, MULTIPLE). Mammalian P-glycoproteins are encoded by small mdr gene families. There are several isotypes in multiple species. NOTE: a carrier protein causing multidrug resist; P stands for "permeability"
Patient education
The teaching or training of patients concerning their own health needs
Peptide peptidohydrolases
A subclass of enzymes of the hydrolase class that catalyzes the hydrolysis of peptide bonds. These comprise the exopeptidases and endopeptidases, also called peptide hydrolase. (From Dorland, 28th ed)
Phospholipase C
An enzyme found in the alpha-toxin of Clostridium welchii and other strains of clostridia and bacilli. It hydrolyzes glycerophosphatidates with the formation of 1,2-diacylglycerol and a phosphorylated nitrogenous base such as choline.
Phosphoric Monoester Hydrolases
A group of hydrolases which catalyze the hydrolysis of monophosphoric esters with the production of one mole of orthophosphate
Phosphotransferases (Alcohol Group Acceptor)
A group of enzymes that transfers a phosphate group onto an alcohol group acceptor
Plasmin
A product of the lysis of plasminogen (profibrinolysin) by plasminogen activators. It is composed of two polypeptide chains, light (B) and heavy (A), with a molecular weight of 75,000. It is the major proteolytic enzyme involved in blood clot retraction or the lysis of fibrin and quickly inactivated by antiplasmins. NOTE: a fibrinolytic agent; a serine proteinase. PHARMACOLOGIC ACTION: Fibrinolytic Agents
Plasminogen Activators
A heterogeneous group of proteolytic enzymes that convert plasminogen to plasmin. They are concentrated in the lysosomes of most cells and in the vascular endothelium, particularly in the vessels of the microcirculation
Plasminogen Inactivators
Important modulators of the activity of plasminogen activators. Four inhibitors, all belonging to the serpin family of proteins, have been implicated in plasminogen activation inhibition. They are PAI-1, PAI-2, protease-nexin, and PROTEIN C INHIBITOR (PAI-3). All inhibit both the tissue-type and urokinase-type plasminogen activators. PHARMACOLOGIC ACTION: Serine Proteinase Inhibitors
Platelet-Derived Growth Factor
Mitogenic peptide growth hormone carried in the alpha-granules of platelets. It is released when platelets adhere to traumatized tissues. Connective tissue cells near the traumatized region respond by initiating the process of replication
Ploidies
The degree of replication of the chromosomes set in the karyotype
Point Mutation
A mutation caused by the substitution of one nucleotide for another. This results in the DNA molecule having a change in a single base pair
Polymorphism (Genetics)
The regular and simultaneous occurrence in a single interbreeding population of two or more discontinuous genotypes. The concept includes chromosome polymorphism
Polymorphism, Restriction Fragment Length
Variation occurring within a species in the length of DNA fragments generated by a specific endonuclease. Such variations are generated by mutations that create or abolish recognition sites for these enzymes
Polymorphism, Single-Stranded Conformational
Variation occurring within a species in the conformation of denatured DNA fragments. These single-stranded DNA fragments are allowed to partially renature in a way that prevents the formation of double-stranded DNA. The fragments are run on polyacrylamide gels under various conditions to detect subtle changes in migration due to altered secondary structure. The resulting bands will align themselves if the fragments are the same, but will misalign if any point mutations are present. SSCPs have been used in detecting mutations in various genes, such as oncogenes, tumor suppressor genes, and genes responsible for genetic diseases
Polyploidy
The chromosomal constitution of a cell containing multiples of the normal number of chromosomes; includes triploidy (symbol: 3N), tetraploidy (symbol: 4N), etc.
Prognosis
A forecast as to the probable outcome of an attack of disease; the prospect as to recovery from a disease as indicated by the nature and symptoms of the case. (Dorland, 27th ed)
Prolactin
Pituitary lactogenic hormone. A polypeptide hormone with a molecular weight of about 23,000. It is essential in the induction of lactation in mammals at parturition and is synergistic with estrogen. The hormone also brings about the release of progesterone from lutein cells, which renders the uterine mucosa suited for the embedding of the ovum should fertilization occur. NOTE: a neurotransmitter pituitary lactogenic hormone
Proliferating Cell Nuclear Antigen
Nuclear antigen with a role in DNA synthesis, DNA repair, and cell cycle progression. PCNA is required for the coordinated synthesis of both leading and lagging strands at the replication fork during DNA replication. PCNA expression correlates with the proliferation activity of several malignant and non-malignant cell types. NOTE: a nuclear protein
Prostate-Specific Antigen
Kallikrein-like serine proteinase produced by epithelial cells of both benign and malignant prostate tissue. It is an important marker for the diagnosis of prostate cancer. NOTE: a serine proteinase produced by prostate cancer; do not confuse with prostate-specific acid phosphatase ( = PROSTATE + ACID PHOSPHATASE)
Prostatic Hyperplasia
Enlargement or overgrowth of the prostate gland as a result of an increase in the size of its constituent cells. NOTE: non-neoplastic despite X refs ADENOMA, PROSTATIC & PROSTATIC ADENOMA
Prostatic Intraepithelial Neoplasia
A premalignant change arising in the prostatic epithelium, regarded as the most important and most likely precursor of prostatic adenocarcinoma. The neoplasia takes the form of an intra-acinar or ductal proliferation of secretory cells with unequivocal nuclear anaplasia, which corresponds to nuclear grade 2 and 3 invasive prostate cancer
Protein Binding
The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments. Do not confuse with BINDING PROTEINS see CARRIER PROTEINS
Protein Isoprenylation
A post-translational modification of proteins by the attachment of an isoprenoid to the C-terminal cysteine residue. The isoprenoids used, farnesyl diphosphate or geranylgeranyl diphosphate, are derived from the same biochemical pathway that produces cholesterol
Protein Kinase C
An enzyme that phosphorylates proteins on serine or threonine residues in the presence of physiological concentrations of calcium and membrane phospholipids. The additional presence of diacylglycerols markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by phorbol esters and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters
Protein p34cdc2
Phosphoprotein with protein kinase activity that functions in the G2/M phase transition of the cell cycle. It is the catalytic subunit of the MATURATION-PROMOTING FACTOR and complexes with both cyclin A and cyclin B in mammalian cells. The maximal activity of p34cdc2 is achieved when it is fully dephosphorylated. Protein p34cdc2, the product of the cdc2 gene in Schizosaccharomyces pombe, should not be confused with the unrelated product of the CDC2 gene in Saccharomyces cerevisiae that forms the large subunit of DNA polymerase III. NOTE: a maturation-promoting factor; cdc refers to "cell division cycle"
Protein p53
Nuclear phosphoprotein encoded by the p53 gene (GENES, P53) whose normal function is to control cell proliferation. A mutant or absent p53 protein has been found in leukemia, osteosarcoma, lung cancer, and colorectal cancer. NOTE: a nuclear protein
Protein Processing, Post-Translational
Any of various enzymically catalyzed post-translational modifications of peptides or proteins in the cell of origin. These modifications include carboxylation, hydroxylation, acetylation, phosphorylation, methylation, glycosylation, oxidation-reduction, degradation and lysis, peptide bond formation, and changes in molecular weight and electrophoretic motility.
Protein Splicing
Excision of in-frame internal protein sequences (inteins) of a precursor protein, coupled with ligation of the flanking sequences (exteins). Protein splicing is an autocatalytic reaction and results in the production of two proteins from a single primary translation product: the intein and the mature protein
Protein-Serine-Threonine Kinases
A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors
Protein-Tyrosine Kinase
An enzyme that catalyzes the phosphorylation of tyrosine residues in proteins with ATP or other nucleotides as phosphate donors
Protein-Tyrosine-Phosphatase
An enzyme group that specifically dephosphorylates phosphotyrosyl residues in selected proteins. Together with PROTEIN-TYROSINE KINASE, it regulates tyrosine phosphorylation and dephosphorylation in cellular signal transduction and may play a role in cell growth control and carcinogenesis
Proto-Oncogene Proteins
Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity
Proto-Oncogene Proteins c-erbb-2
Cellular proteins in the epidermal growth factor receptor family encoded by the c-erbB genes. These proteins are overexpressed in a significant portion of adenocarcinomas found at various sites, especially in the breast. Gene amplification appears to be the predominant method leading to overexpression
Proto-Oncogene Proteins c-fos
Cellular DNA-binding proteins encoded by the c-fos genes (GENES, FOS). They are involved in growth-related transcriptional control. c-fos combines with c-jun (PROTO-ONCOGENE PROTEINS C-JUN) to form a c-fos/c-jun heterodimer (TRANSCRIPTION FACTOR AP-1) that binds to the TRE (TPA-responsive element) in promoters of certain genes
Proto-Oncogene Proteins c-jun
Cellular DNA-binding proteins encoded by the c-jun genes (GENES, JUN). They are involved in growth-related transcriptional control. There appear to be three distinct functions: dimerization (with c-fos), DNA-binding, and transcriptional activation. Oncogenic transformation can take place by constitutive expression of c-jun
Proto-Oncogene Proteins c-myc
Cellular DNA-binding proteins encoded by the c-myc genes. They are normally involved in nucleic acid metabolism and in mediating the cellular response to growth factors. Elevated and deregulated (constitutive) expression of c-myc proteins can cause tumorigenesis
Proto-Oncogenes
Normal cellular genes homologous to viral oncogenes. The products of proto-oncogenes are important regulators of biological processes and appear to be involved in the events that serve to maintain the ordered procession through the cell cycle. Proto-oncogenes have names of the form c-onc

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RAS Proteins
Small GTP-binding proteins encoded by ras genes (GENES, RAS) that play a critical role in normal cellular growth, differentiation, and development, and have the potential for malignant transformation. Two of the major ras proteins include the normal cellular form, PROTO-ONCOGENE PROTEIN P21(RAS), and the malignant form, ONCOGENE PROTEIN P21(RAS). NOTE: GTP-binding proteins; ras derived from "Retrovirus Associated Sequences"
Receptor Protein-Tyrosine Kinase
A catalytic PROTEIN-TYROSINE KINASE domain found on the cytoplasmic beta-portion of receptors. Many growth and differentiation factor receptors contain this domain. It is critical for the signal transduction pathways required for mitogenesis, transformation, and cell differentiation. (Neuron 1992;9:383)
Receptors, Androgen
Proteins, generally found in the cytoplasm, that specifically bind androgens and mediate their cellular actions. The complex of the androgen and receptor migrates to the nucleus where it induces transcription of specific segments of DNA
Receptors, Calcitriol
Proteins, usually found in the cytoplasm, that specifically bind calcitriol, migrate to the nucleus, and regulate transcription of specific segments of DNA. Vitamin D is converted in the liver and kidney to calcitriol and ultimately acts through these receptors
Receptors, Cell Surface
Cell surface proteins that bind signalling molecules external to the cell with high affinity and convert this extracellular event into one or more intracellular signals that alter the behavior of the target cell (From Alberts, Molecular Biology of the Cell, 2nd ed, pp693-5). Cell surface receptors, unlike enzymes, do not chemically alter their ligands
Receptors, cytoplasmic and nuclear
Proteins in the cytoplasm or nucleus that specifically bind signalling molecules and trigger changes which influence the behavior of cells. The major groups are the steroid hormone receptors, which usually are found in the cytoplasm, and the thyroid hormone receptors, which usually are found in the nucleus. Receptors, unlike enzymes, generally do not catalyze chemical changes in their ligands
Receptors, Epidermal Growth Factor-Urogastrone
Glycoproteins of about 170 kD that have protein kinase activity and span the plasma membranes of growing cells, including tumors. They are activated by the binding of EPIDERMAL GROWTH FACTOR-UROGASTRONE which then initiates DNA and protein synthesis. They are not found on mitotically quiescent cells except in the stomach where they control the synthesis and release of digestive enzymes and gastric acid. TRANSFORMING GROWTH FACTOR ALPHA also binds to and activates these receptors
Receptors, Estradiol
Cytoplasmic proteins that bind estradiol, migrate to the nucleus, and regulate DNA transcription
Receptors, Estrogen
Cytoplasmic proteins that bind estrogens and migrate to the nucleus where they regulate DNA transcription. Evaluation of the state of estrogen receptors in breast cancer patients has become clinically important
Receptors, Glucocorticoid
Cytoplasmic proteins that specifically bind glucocorticoids and mediate their cellular effects. The glucocorticoid receptor-glucocorticoid complex acts in the nucleus to induce transcription of DNA. Glucocorticoids were named for their actions on blood glucose concentration, but they have equally important effects on protein and fat metabolism. Cortisol is the most important example
Receptors, Mineralocorticoid
Cytoplasmic proteins that specifically bind mineralocorticoids and mediate their cellular effects. The receptor with its bound ligand acts in the nucleus to induce transcription of specific segments of DNA. Mineralocorticoids were named for their actions on extracellular electrolyte concentrations. The most important example is aldosterone
Receptors, Progesterone
Specific proteins found in or on cells of progesterone target tissues that specifically combine with progesterone. The cytosol progesterone-receptor complex then associates with the nucleic acids to initiate protein synthesis. There are two kinds of progesterone receptors, A and B. Both are induced by estrogen and have short half-lives
Receptors, prolactin
Labile proteins on or in prolactin-sensitive cells that bind prolactin initiating the cells' physiological response to that hormone. Mammary casein synthesis is one of the responses. The receptors are also found in placenta, liver, testes, kidneys, ovaries, and other organs and bind and respond to certain other hormones and their analogs and antagonists. This receptor is related to the growth hormone receptor
Receptors, Retinoic Acid
Proteins in the nucleus or cytoplasm that specifically bind retinoic acid or retinol and trigger changes in the behavior of cells. Retinoic acid receptors, like steroid receptors, are ligand-activated transcription regulators. Several types have been recognized
Receptors, Steroid
Proteins found usually in the cytoplasm or nucleus that specifically bind steroid hormones and trigger changes influencing the behavior of cells. The steroid receptor-steroid hormone complex regulates the transcription of specific genes
Retinoblastoma protein
Product of the retinoblastoma tumor suppressor gene. It is a nuclear phosphoprotein hypothesized to normally act as an inhibitor of cell proliferation. Rb protein is absent in retinoblastoma cell lines. It also has been shown to form complexes with the adenovirus E1A protein, the SV40 T antigen, and the human papilloma virus E7 protein
Retinoids
Derivatives of vitamin A. Used clinically in the treatment of severe cystic acne, psoriasis, and other disorders of keratinization. Their possible use in the prophylaxis and treatment of cancer is being actively explored. NOTE: dermatol agents
RNA Editing
A process that changes the nucleotide sequence of mRNA from that of the DNA template encoding it. Some major classes of RNA editing are as follows: 1) the conversion of cytosine to uracil in mRNA; 2) the addition of variable number of guanines at pre-determined sites; and 3) the addition and deletion of uracils, templated by guide-RNAs (RNA, GUIDE). NOTE: a type of post-transcriptional RNA processing
RNA, Neoplasm
RNA present in neoplastic tissue
RNA Processing, Post-Transcriptional
Post-transcriptional biological modification of messenger, transfer, or ribosomal RNAs or their precursors. It includes cleavage, methylation, thiolation, isopentenylation, pseudouridine formation, conformational changes, and association with ribosomal protein
RNA Splicing
The ultimate exclusion of nonsense sequences or intervening sequences (introns) before the final RNA transcript is sent to the cytoplasm. NOTE: a physiol process taking place within the cell nucleus; do not confuse with DNA, RECOMBINANT; CLONING, MOLECULAR or GENETIC INTERVENTION
RNA-Directed DNA Polymerase
An enzyme that synthesizes DNA on an RNA template. It is encoded by the pol gene of retroviruses and by certain retrovirus-like elements

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Sequence Deletion
Deletion of sequences of bases or amino acids from the genetic material of an individual. Evidence for these deletions may be obtained by cytological methods
Serine Proteinase Inhibitors
Exogenous or endogenous compounds which inhibit serine proteinases
Serine Proteinases
Peptide hydrolases which have an active center histidine and serine involved in the catalytic process. This group of enzymes is inactivated by organic fluorophosphates such as diisopropylphosphofluoridate (DIPF)
Sermorelin
Human growth hormone-releasing factor(1-29)amide. The biologically active fragment of SOMATOTROPIN-RELEASING HORMONE. It is used to stimulate growth in children with a growth hormone deficiency or insufficiency. NOTE: a somatotropin-releasing hormone
Serpins
A family of serine proteinase inhibitors which are similar in amino acid sequence and mechanism of inhibition, but differ in their specificity toward proteolytic enzymes. This family includes alpha 1-antitrypsin, angiotensinogen, ovalbumin, antiplasmin, alpha 1-antichymotrypsin, thyroxine-binding protein, complement 1 inactivators, antithrombin III, heparin cofactor II, plasminogen inactivators, gene Y protein, placental plasminogen activator inhibitor, and barley Z protein. Some members of the serpin family may be substrates rather than inhibitors of serine proteinases, and some serpins occur in plants where their function is not known. NOTE: "a family of SERine Proteinase INhibitors", thus the source of the name. PHARMACOLOGIC ACTION: Serine Proteinase Inhibitors
Sex Hormone-Binding Globulin
A glycoprotein migrating as a beta-globulin. Its molecular weight, 52,000 or 95,000-115,000, indicates that it exists as a dimer. The protein binds testosterone, dihydrotestosterone, and estradiol in the plasma. Changes in its concentration significantly affect the ratio of unbound (biologically active) testosterone to estradiol in plasma. NOTE: refers to a specific protein in the blood binding only testosterone or estradiol; for other sex hormone-binding globulins consider ANDROGEN-BINDING PROTEINS & PROGESTERONE-BINDING GLOBULIN
Sialic acids
A group of naturally occurring N-and O-acyl derivatives of the deoxyamino sugar neuraminic acid. They are ubiquitously distributed in many tissues
Signal Transduction
The intercellular or intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GABA-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway
Sodium Channels
Cell membrane glycoproteins selective for sodium ions. Fast sodium current is associated with the action potential in neural membranes
Somatomedins
Insulin-like polypeptides made by the liver and some fibroblasts and released into the blood when stimulated by SOMATOTROPIN. They cause sulfate incorporation into collagen, RNA, and DNA synthesis, which are prerequisites to cell division and growth of the organism. NOTE: neurotransmitters
Somatostatin
A polypeptide hormone produced in the hypothalamus that inhibits the release of SOMATOTROPIN. Somatostatin is also a neurotransmitter in the central and peripheral nervous systems and is released by the delta-cells of the pancreas. NOTE: a neurotransmitter hypothalamic hormone. PHARMACOLOGIC ACTION: Hormone Antagonists
Superoxide dismutase
An oxidoreductase that catalyzes the reaction between superoxide anions and hydrogen to yield molecular oxygen and hydrogen peroxide. The enzyme protects the cell against dangerous levels of superoxide
Suppression, Genetic
The restoration of the wild-type phenotype in an organism possessing a mutationally altered genotype. The effects of the mutation may be suppressed by a second "suppressor" mutation on a different gene, by a suppressor mutation on the same gene but located at a distance from the site of the primary mutation, or by the presence of a cytoplasmic suppressor due to a change in non-chromosomal DNA
Synaptophysin
A 38-kDa integral membrane glycoprotein of the presynaptic vesicles in neuron and neuroendocrine cells. It is expressed by a variety of normal and neoplastic neuroendocrine cells and is therefore used as an immunocytochemical marker for neuroendocrine differentiation in various tumors. In ALZHEIMER'S DISEASE and other dementing disorders there is an important synapse loss due in part to a decrease of synaptophysin in the presynaptic vesicles

T

Telomerase
Essential ribonucleoprotein reverse transcriptase that adds telomeric DNA to the ends of eukaryotic chromosomes. Telomerase appears to be repressed in normal human somatic tissues but reactivated in cancer, and thus may be necessary for malignant transformation
Testosterone
The major androgenic hormone produced by the interstitial (Leydig) cells of the testes in response to stimulation by the luteinizing hormone of the anterior pituitary. It regulates gondotropic secretion and wolfian duct differentiation, and stimulates skeletal muscle. It is also responsible for other male characteristics and spermatogenesis after its conversion to dihydrotestosterone. In addition testosterone possesses protein anabolic properties, and it is converted to estradiol in peripheral tissue. (From Dorland, 28th ed) . PHARMACOLOGIC ACTION: Antineoplastic Agents, Hormonal
Testosterone 5-alpha-reductase
3-Oxo-5 alpha-steroid:(acceptor) delta(4)-oxidoreductase
Tissue Polypeptide Antigen
Serological tumor marker composed of a molecular complex of cytokeratins 8, 18, and 19. It is used in the diagnosis and staging of bronchogenic carcinoma
Trans-Activation (Genetics)
Increased rate of gene expression directed by either viral or cellular proteins. These regulatory factors (diffusible gene products) act in trans -- that is, act on homologous or heterologous molecules of DNA. (Cis-acting factors act only on homologous molecules)
Trans-Activators
Diffusible gene products that act on homologous or heterologous molecules of viral or cellular DNA to regulate the expression of proteins
Transcription factor, sp1
Promoter-specific RNA polymerase II transcription factor that binds to the GC box, one of the upstream promoter elements (UPE) in mammalian cells. The binding of Sp1 is necessary to initiate transcription in the promoters of a variety of cellular and viral genes including c-Ha-ras and HIV
Transcription, Genetic
The transfer of genetic information from DNA to messenger RNA by DNA-directed RNA polymerase. It includes reverse transcription and transcription of early and late genes expressed early in an organism's life cycle or during later development
Transferrin
Serum beta-globulin that binds and transports iron. (From Dorland, 28th ed)
Transformation, Genetic
The unidirectional transfer and incorporation of foreign DNA by prokaryotic or eukaryotic cells and the subsequent recombination of part or all of that DNA into the cell's genome. (Glossary of Genetics: Classical and Molecular, 5th ed)
Transforming Growth Factor alpha
Factor isolated in a variety of tissues including epithelium, and maternal decidua. It is closely related to epidermal growth factor (EPIDERMAL GROWTH FACTOR-UROGASTERONE) and binds to the EGF receptor. TGF-alpha acts synergistically with TGF-beta in inducing phenotypic transformation, but its physiological role is unknown
Transforming Growth Factor beta
Factor synthesized in a wide variety of tissues including platelets, placenta, and both normal and transformed cell lines. It acts synergistically with TGF-alpha in inducing phenotypic transformation and can also act as a negative autocrine growth factor. TGF-beta also has a potential role in embryonal development, cellular differentiation, hormone secretion, and immune function. There are at least three forms of TGF-beta: TGF-beta1, TGF-beta2, and TGF-beta1.2. The latter is a heterodimer made up of both TGF-beta1 and TGF-beta2
Transforming Growth Factors
Hormonally active polypeptides that can induce the transformed phenotype when added to normal, non-transformed cells. They have been found in culture fluids from retrovirally transformed cells and in tumor-derived cells as well as in non-neoplastic sources. Their transforming activities are due to the simultaneous action of two otherwise unrelated factors, TRANSFORMING GROWTH FACTOR ALPHA and TRANSFORMING GROWTH FACTOR BETA
Translation, Genetic
Formation of peptides on ribosomes, directed by messenger RNA. NOTE: do not confuse with TRANSLOCATION (GENETICS), a chromosome aberration
Translocation(Genetics)
A type of aberration characterized by fragmentation of a chromosome and transfer of the broken-off portion to another chromosome, often of a different pair. NOTE: do not confuse with TRANSLATION, GENETIC (RNA-directed formation of peptides)
Tubulin
A microtubule subunit protein found in large quantities in mammalian brain. It has also been isolated from sperm flagella, cilia, and other sources. Structurally, the protein is a dimer with a molecular weight of approximately 120,000 and a sedimentation coefficient of 5.8S. It binds to colchicine, vincristine, and vinblastine. NOTE: a nerve tissue protein
Tumor Markers, Biological
Molecular products metabolized and secreted by neoplastic tissue and characterized biochemically in cells or body fluids. They are indicators of tumor stage and grade as well as useful for monitoring responses to treatment and predicting recurrence. Many chemical groups are represented including hormones, antigens, amino and nucleic acids, enzymes, polyamines, and specific cell membrane proteins and lipids
Tumor Necrosis Factor
Serum glycoprotein produced by activated macrophages and other mammalian mononuclear leukocytes which has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. It mimics the action of endotoxin but differs from it. It has a molecular weight of less than 70,000 kDa. NOTE: a blood protein
Tumor Suppressor Proteins
Proteins that are normally involved in holding cellular growth in check. Deficiencies or abnormalities in these proteins may lead to unregulated cell growth and tumor development.

U

Up-Regulation (Physiology)
Process that increases ligand/receptor interactions due to an increase in the number of available receptors. NOTE: "regulation" refers to ligand/receptor interactions
Urokinase
Proteolytic enzyme that converts plasminogen to plasmin where the preferential cleavage is between arginine and valine. It was isolated originally from human urine, but is found in most tissues of most vertebrates. Urokinase is used in the therapy of thromboembolic conditions. NOTE: a serine proteinase & plasminogen activator

V

Vasoactive Intestinal Peptide
A highly basic, single-chain polypeptide isolated from the intestinal mucosa. It has a wide range of biological actions affecting the cardiovascular, gastrointestinal, and respiratory systems. It is also found in several parts of the central and peripheral nervous systems and is a neurotransmitter. NOTE: a neurotransmitter gastrointestinal hormone
Vasoactive Intestinal Peptide
A highly basic, single-chain polypeptide isolated from the intestinal mucosa. It has a wide range of biological actions affecting the cardiovascular, gastrointestinal, and respiratory systems. It is also found in several parts of the central and peripheral nervous systems and is a neurotransmitter. NOTE: a neurotransmitter gastrointestinal hormone
Vitamins
A general term for a number of unrelated organic substances that occur in many foods in small amounts and that are necessary in trace amounts for the normal metabolic functioning of the body. They may be water-soluble or fat-soluble. (Dorland, 28th ed)

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X

Y

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Date de création: 05 avril 1999  --  Dernière mise à jour : Novembre 2012   --  Responsable: C. Delvenne
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