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Oncology Glossary

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M-CSF (macrophage colony-stimulating factor): a secreted cytokine synthesized by mesenchymal cells. By binding to its receptors, M-CSF stimulates the survival, proliferation, and differentiation of hematopoietic cells of the monocyte-macrophage lineage. It may also be involved in the development of the placenta.

M2 phenotype (type II macrophages, M2 polarized macrophages): under the stimulation of specific cytokines (eg, interleukin [IL] -4, IL-10, IL-13, M-CSF but not GM-CSF, LPS, INF-γ) macrophages tune inflammation and adaptive immunity; promote cell proliferation by producing growth factors and products of the arginase pathway; scavenge debris by expressing scavenger receptors; promote angiogenesis, tissue remodeling, and repair and suppress adaptive immunity.

MAb 225: see cetuximab.

MAb h-R3: a humanized monoclonal antibody targeted against the epidermal growth factor receptor (EGFR). Mab h-R3 is a neutralizing antibody that prevents binding of ligand to EGFR, thereby inhibiting ligand-mediated activation of EGFR.

macrometastasis: a cohesive cluster of metastatic tumor cells more than 2 mm in the largest dimension within a lymph node.

macrophages (Mφ): macrophages that originate from monocytes that belong to the innate immune system. The primary types are peritoneal macrophages, alveolar macrophages, histiocytes, Kupffer cells of the liver, and osteoclasts. They act in nonspecific defense (or innate immunity) as well as specific defense (or cell-mediated immunity) of vertebrate animals. Their role is to phagocytose cellular debris and pathogens either as stationary or mobile cells and to stimulate lymphocytes and other immune cells to respond to the pathogen.

Mad: a family of proteins with basic helix-loop-helix motifs that shows transcriptional repressor activity.

MAF: gene coding for MAF, which belongs to the basic region-leucine zipper (bZIP) family of transcriptional factors. Members of the family are c-Maf, MafA, MafB, and NRL. Maf proteins differ from the canonical bZIP proteins in the length of the DNA-recognition sequence and a requirement of a region outside the bZIP region for specific DNA binding. The gene is involved in t(14;16)(q32;q23) chromosomal translocation found in a limited fraction (less than 5%) of patients with multiple myeloma.

MAFB: gene coding for MafB. The gene is involved in t(14;20)(q32;q11) chromosomal translocation found in a limited fraction (less than 5%) of patients with multiple myeloma. See MAF.

MAGE genes: genes that are typically silent in normal tissues but expressed in several cancers. For example, MAGE-1 directs the expression of a tumor antigen recognized in melanoma by autologous cytolytic T lymphocytes. See MAGE-1.

MAGE-1: a member of the MAGEA1 family that is expressed at high levels in tumors of various histologic origins and typically silent in normal tissues. MAGE-1 has a CpG-rich promoter region that is methylated in most normal tissues.

MAGE-1.A1: a peptide of MAGE-1(amino acids 161-169) that is presented by HLA-A1. The same peptide can also be presented by HLA-B35.

MAGE-3: protein encoded by the MAGE A locus. See MAGE genes.

MAGE-3.A1 antigen: a nonapeptide of MAGE-3 (amino acids 168-176) that is presented by HLA-A1. The same peptide can also be presented by HLA-B35.

MAGE-3.A24: a peptide of MAGE-3 (amino acids 195-203) that is HLA-A24–restricted.

MAGE-A1: protein encoded by the MAGE A locus. See MAGE genes.

MAGE-A3: protein encoded by the MAGE A locus. See MAGE genes.

magnetic resonance imaging: a procedure in which radio waves and a powerful magnet linked to a computer are used to create detailed pictures of areas inside the body. These pictures can show the difference between normal and diseased tissue.

maintenance therapy: therapy intended to prolong the benefit (eg, disease remission) experienced by a patient from a prior primary treatment (eg, chemotherapy).

male-pattern baldness: also known as androgenic alopecia, a progressive scalp hair loss in a distinct pattern resulting from androgenic miniaturization of hair follicles. Generally three zones of the scalp are preferentially affected in a progression of bitemporal recession, frontal hairline recession, and hair thinning on the crown.

malignant peripheral nerve sheath tumor (MPNST): an aggressive soft tissue cancer that arises in cells surrounding the peripheral nerves.

mammaglobin: a glycoprotein that is mostly, although not exclusively, confined to breast tissue. Expression of mammaglobin in nonbreast tissue is associated with the metastasis of breast cancer and may be upregulated in breast cancer.

mammalian target of rapamycin (mTOR): member of a protein complex (along with raptor and GβL) that is used by cells to sense nutrients in the environment. mTOR is a serine/threonine kinase that is activated by AKT and regulates protein synthesis on the basis of nutrient availability. It was discovered when rapamycin, a drug used in transplantation, was shown to block cell growth presumably by blocking the action of mTOR.

Manhattan plot: in a genome-wide association study, the display of negative log (P values) on the y-axis for single nucleotide polymorphisms across the 22 autosomes and sex chromosomes on the x-axis. The higher the point lies on the y-axis, the lower the P value and the greater the significance.

MAP kinase pathway: signal transduction pathway important for survival and proliferative signals through the activation of Ras, BRAF, MEK, and ERK.

mapatumumab: also called HGS-ETR1 or TRM-1 mAb. Designed to function as an agonist, mapatumumab is a humanized monoclonal antibody directed against TRAIL-R1. It mimics the activity of TRAIL by binding to TRAIL-R1 to induce apoptosis.

MAPK (mitogen-activated protein kinase): a family of enzymes that form an integrated network influencing cellular functions such as differentiation, proliferation, and cell death. These cytoplasmic proteins modulate the activities of other intracellular proteins by adding phosphate groups to their serine/threonine amino acids.

MAPKK (mitogen-activated protein kinase kinase): another name for MEK. See MEK (MAPK-ERK kinase).

MART-1: a melanoma-related antigen. MART-1 is absent in all normal cells except for melanocytes and the retina. In addition, apart from melanomas, MART-1 has not been observed in any other cancers. Consequently, the MART-1 antigen is considered to have a melanoctye lineage.

Masscode: a system designed by BioServe (Laurel, MD) that is a high-throughput genotyping process, which uses a polymerase chain reaction–based, allele-specific discrimination assay measured by means of cleavable mass spectrometry tags.

massively parallel sequencing: a high-throughput approach to sequencing DNA or RNA, also known as next-generation or second-generation sequencing.

matrix-assisted laser desorption and ionization (MALDI): a soft ionization technique used in time-of flight mass spectrometry, allowing the analysis of proteins and peptides, which fragment when ionized by a laser beam. A matrix is used to protect the biomolecule from being destroyed by direct laser beam and to facilitate vaporization and ionization.

matrix-degrading factors: proteases involved in the degradation of extracellular matrix (ECM) components, a process regulated by proteases and protease inhibitors. Several growth factors stimulate protease production, which leads to ECM degradation. Thus, epidermal growth factor, platelet-derived growth factor, basis fibroblast growth factor, and interleukin-1 (IL-2) induce the expression of ECM-degrading proteinases and their activators (eg, metalloproteinases and plasminogen activators).

matrix-producing factors: involved in the formation of the extracellular matrix (ECM), a complex structure that surrounds and supports cells within mammalian tissues. The biologic molecules that constitute this structure can be classified as structural proteins (eg, collagen and elastin), specialized proteins (eg, fibrillin, fibronectin, and laminin) and proteoglycans (proteins with complex carbohydrates).

matrix proteinases: see MMP (matrix metalloprotease [metalloproteinases]).

Max: a transcriptional modulator that can heterodimerize with Mad or myc proteins, enhancing transcriptional repression or activation, respectively. See Mad.

Maxamine: the trade name (Maxim Pharmaceuticals, San Diego, CA) for histamine dihydrochloride, which is being investigated for its antitumor effects. Its mechanism of action is possibly related to its ability to maintain the activity of natural killer cells while inhibiting the suppressive action of monocytes. Thus, it works synergistically with cytokines such as interleukin-2 and interferon alfa to inhibit the growth of cancer cells in vivo.

maximum efficacious dose: the dose above which no significant improvement in efficacy is obtained.

MBD2: member of the class of nuclear proteins related by the presence of a methyl CpG-binding domain and is capable of binding methylated DNA, thereby preventing transcription from methylated gene promoters.

MBPs (methyl-CpG binding proteins): inhibit transcription by binding methylated DNA and other proteins that regulate transcription.

MC1R (melanocortin-1 receptor): a Gs-protein coupled receptor primarily expressed in cutaneous and hair follicle melanocytes. MC1R is activated by α-melanocyte stimulating hormone or adrenocorticotropin. Many MC1R allelic variants exist in nature; these mutants correlate with phenotypes, such as red hair, associated with greater ultraviolet radiation sensitivity and melanoma risk.

M-CGH (metaphase comparative genomic hybridization): a relatively new molecular cytogenetic technique that detects DNA sequence copy number changes throughout the genome in a single hybridization. The method is based on cohybridization of differentially labeled tumor and normal DNA to human metaphase chromosomes. Alterations, classified as DNA gains and losses, reveal a characteristic pattern that includes mutations at chromosomal and subchromosomal levels. Gains and losses of DNA sequences of approximately 2 to 20 Mb can be detected by this method.

Mcl-1: an anti-apoptotic protein belonging to the Bcl-2 family. Mcl-1 was first identified in human myeloblastic leukemia cell line that was induced to differentiate along the monocyte lineage.

MCM (minichromosome maintenance) proteins: essential for eukaryotic genome replication. MCM proteins form a hexameric complex and are important components involved in the formation of replication forks and in recruiting DNA replication–related proteins. The MCM2, 4, 6, and 7 complex possesses DNA helicase activity, which has a role in regulating DNA replication.

MCM2: see MCM (minichromosome maintenance) proteins.

MCM6: see MCM (minichromosome maintenance) proteins.

MCP1 (monocyte chemoattractant protein-1): a macrophage chemotactic protein also known as chemokine (C-C motif) ligand 2 (CCL2). MCP1 is a member of the small inducible gene (SIG) family.

MDM2: an E3 ubiquitin ligase that recognizes the N-terminal activation domain (TAD) of proteins belonging to the p53 family. By blocking the ability of p53 to associate with factors involved in protein transcription, the MDM2 interaction with p53 prevents transcriptional activation. In addition, interaction with p53 leads to ubiquitinylation and subsequent degradation of p53. See proteasome and ubiquitin.

MDP (melanocytic differentiation protein): protein expressed by melanocytes and by melanoma cells, typically functioning as part of the melanin synthetic pathway. Examples include tyrosinase, gp100, and MART-1/melan-A.

MDR-1: gene encoding P-glycoprotein.

MDS-EVI1 (myelodysplastic syndrome 1–ecotropic viral integration 1 site): a fusion protein that occurs as a result of a chromosomal translocation [t(3;3)(q21;q26)] or inversion [inv(3)(q21q26)] lacking the SET domain.

MDX-010: a fully human anti-CTLA-4 antibody. MDX-010 has been granted orphan-drug designation by the US Food and Drug Administration for the treatment of melanoma as well as other types of solid tumors.

MEK (MAPK-ERK kinase): a protein kinase activated by c-Raf through phosphorylation of specific serine residues. Activation of ERK by activated MEK may lead to translocation of ERK to the nucleus, resulting in the activation of specific transcription factors.

MEK1: an isoform of MEK. See MEK (MAPK-ERK kinase).

MEK2: an isoform of MEK. See MEK (MAPK-ERK kinase).

MEK/MAP/ERK kinase: a family of kinases that activates the MAPK family of proteins through phosphorylation of both a threonine and tyrosine residue. These kinases belong to the signal transduction pathway governing proliferation. Growth factors involved in proliferative pathways (such as epidermal growth factor, fibroblast growth factor, and platelet-derived growth factor) are the extracellular stimuli that activate these kinases.

melan-A/MART-1: a melanoma-related antigen. MART-1 is absent in all normal cells except for melanocytes and the retina. In addition, apart from melanomas, MART-1 has not been observed in any other cancers. Consequently, the MART-1 antigen is considered to have a melanocyte lineage.

Merkel cells: cells universally present in the skin of vertebrates at a low frequency. They are found particularly in sensitive and tactile areas, where they primarily come into contact with sensory neurons and have thus been associated with the sense of discrimination between shapes and textures. Merkel cells belong to the neuroendocrine system because they secrete a wide spectrum of hormones and neurotransmitters. They can turn malignant and are then responsible for the development of the skin tumor known as Merkel cell carcinoma.

mesorectal fascia: the thin layer of visceral fascia enclosing the mesorectum.

mesorectum: the perirectal tissue composed of fat, lymphatics, and blood vessels contained within the endopelvic visceral fascia and extending the length of the rectum.

MET: the receptor for hepatocyte growth factor. MET is a transmembrane receptor tyrosine kinase. The primary single chain precursor protein is post-translationally cleaved to produce the alpha and beta subunits; the mature receptor is composed of these subunits linked via disulfide bonds. Various mutations in the MET gene have been associated with papillary renal carcinoma.

meta-analytic approach: a method that evaluates the predictability of the surrogate end point on the true clinical end point (overall survival) in a series of clinical trials.

metabolic response: tumor glucose use is quantitatively assessed by [18F]fluorodeoxyglucose positron emission tomography (PET) prior to chemotherapy and 14 days after initiation of therapy. Patients are classified as metabolic responders, when the metabolic activity of the primary tumor has decreased by more than 35% at the time of the second PET. This cutoff value is prospectively validated for AEG I, II, III and gastric cancer.

metabolic syndrome: characterized by a group of metabolic risk factors occurring together in one person. These risk factors include abdominal obesity manifested as excessive fat tissue in and around the abdomen, elevated blood levels of triglycerides, decreased blood levels of high-density lipoprotein cholesterol, elevated blood pressure, and elevated fasting blood glucose, which is a measure of glucose intolerance and is also known as insulin resistance.

metabolite: a substance that takes part in the process of metabolism, which involves the breakdown of complex organic constituents of the body with the liberation of energy for use in bodily functioning. The various compounds that take part in or are formed by these reactions are called metabolites.

metagene: a single aggregate measure of the expression of a group of genes that usually show coordinated expression in a set of samples. The metagene value may be defined as the arithmetic mean or the weighted average or some other mathematical combination of the genes of interest.

metalloproteinase: see MMP (matrix metalloprotease [metalloproteinases]).

metastatic castration-resistant prostate cancer (mCRPC): progressive disease despite surgical castration or ongoing use of gonadotropin-releasing hormone agonists with confirmed castrate levels of testosterone.

2-methoxyethyl backbone: third-generation oligonucleotides used in antisense technology. The methoxyethyl backbone substitutes for the conventional phosphodiester backbone found in oligonucleotides, RNA, and DNA.

methyl-binding domains: domains in transcription factors that bind to methyl-CpGs and attract transcriptional repressors.

Methyl-Seq: determines the methylation status of CpG islands (regulatory regions) across the genome, thereby assisting in the interpretation of the activation state of certain genes or regions.

methylation-silenced tumor suppression genes: see DNA methylation and promoter hypermethylation.

methylation-specific polymerase chain reaction: a molecular assay that detects methylation of a particular stretch of DNA.

methylation-specific polymerase chain reaction (MSP): a method used to identify methylated cytosine bases in genomic DNA. Bisulfite treatment deaminates unmethylated cytosine residues into thymidine bases; methylation prevents deamination. Primers specific for methylated and unmethylated DNA sequences are then used in a polymerase chain reaction to amplify respective sequences.

metronomic chemotherapy: a schedule of chemotherapy given at lower doses to allow more frequent administration without the induction of myelosuppression seen with maximum tolerated dose (MTD) regimens. This type of regimen is also called antiangiogenic scheduling as a result of the fact that slowly proliferating (angiogenic) endothelial cells are more efficiently targeted by metronomic chemotherapy than by MTD regimens, resulting in inhibition of tumor growth because of insufficient neovascularization.

MGMT: the DNA repair protein, O6-methylguanine DNA methyltransferase, which confers resistance to alkylating agents. Thus, cells are protected from the toxicity of alkylating agents, which frequently target the O6 position of guanine in DNA.

MGMT gene: gene coding for the DNA repair protein, O6-methylguanine DNA methyltransferase, which confers resistance to alkylating agents. Thus, cells are protected from the toxicity of alkylating agents, which frequently target the O6 position of guanine in DNA.

MHC class I (major histocompatibility complex I): molecules found on almost every nucleated cell of the body. In humans, these are often referred to as human leukocyte antigen (HLA) molecules. These molecules act as signposts by displaying fragments of protein antigens on the cell surface. The presented fragments (epitopes) can be derived from self or nonself (viral) antigens. MHC class I molecules presenting epitopes are recognized by cytotoxic T cells. When a nucleated cell is aberrant (malignant or virally infected), intracellularly derived epitopes that are foreign to circulating T cells will be presented, leading to immune activation. In humans, there are three major loci that encode MHC class I molecules: HLA-A, HLA-B, and HLA-C.

MHC class II (major histocompatibility complex II): molecules found only on a few types of cells in the body, most notably, antigen-presenting cells such as macrophages and dendritic cells. Like MHC class I, these molecules present fragments of protein antigens. Unlike MHC class I, MHC class II peptides are usually derived from extracellular antigens that may be released by bacteria or tumors. MHC class II molecules presenting epitopes are recognized by helper T cells. In humans, there are three major loci that encode MHC class II molecules: human leukocyte antigen (HLA) -DR, HLA-DP, and HLA-DQ.

Mi2: a member of the Swi/Snf family of proteins with helicase and ATPase activities. Mi2 is part of the NuRD complex and is responsible for its chromatin remodeling activity.

Mi2α: see Mi2.

MIBG scintigraphy: a nuclear medicine scan using iodine-123 metaiodobenzylguanidine (MIBG) scintigraphy to identify neuroblastoma or pheochromocytoma lesions.

microarray: a miniature array of regularly spaced DNA or oligonucleotide sequences printed on a solid support at high density that is used in a hybridization assay. The sequences may be cDNAs or oligonucleotide sequences that are synthesized in situ to make a DNA chip.

microarray analysis: see cDNA microarray and tissue microarray.

microarray-based comparative genomic hybridization (array-CGH): a method that uses microarrays to probe changes in chromosomal DNA, thereby identifying precise areas in which genetic changes occur in cancer cells.

microarray expression profiling: the creation of gene expression profiles using microarray technology. See gene expression profile and cDNA microarray.

microarray technology: see cDNA microarray and tissue microarray.

microarray transcriptional profiling: the use of arrays of immobilized cDNAs or oligonucleotides representing gene sequences upon which RNA from various cell types is hybridized and detected. In this manner the expression of thousands of genes expressed in a given cell type can be measured simultaneously.

microenvironment: the unique complex of tumor cells, stromal, and immune infiltrate that can promote or reject tumors as well as shape their phenotype through contact-dependent or soluble mediators.

microglial cell: a type of glial cell that acts as the first and primary form of active immune defense in the CNS.

micrometastasis: a cohesive cluster of metastatic tumor cells measuring more than 0.2 mm and up to 2.0 mm in the largest dimension found within a lymph node.

microRNA profiles: the study of the global expression of microRNAs in tissues.

microRNAs: endogenous noncoding RNAs approximately 22 nucleotides long that regulate gene silencing by post-transcriptional mechanisms such as cleavage or translational repression.

microsatellite DNA: s short tandemly repeated sequence in the DNA of a genome. The short sequences repeat many times (10 to 100) and are frequent in all genomes. More than 10 to 25 repeats tend to harbor polymorphisms. Microsatellite sequences are often used for genetic fingerprinting and are not useful in evolutionary studies as a result of their propensity for mutations.

microsatellite instability: the genomic instability associated with the presence of microsatellites (repeating units in DNA of 1–5 basepairs that are ubiquitous, abundant, and repeated several times in eukaryotic genomes), giving rise to mutations that involve the addition or subtraction of one or two repeat units.

microsatellite instability (MSI): an alteration in the length of the microsatellites from cell to cell.

microsatellite markers: microsatellite sequences often used as markers for genetic fingerprinting and to detect the loss of one of the two alleles of one or more genes.

microsatellites: repeating units of 1-4 DNA base pairs that are distributed widely throughout the genome and have a high degree of repeat length variation in the population. Their length remains stable with cell division and inheritance so they may be used as molecular markers of cell lineage, in population genetic studies or paternity testing.

microvascular invasion: the presence of tumor cells inside the lumen of the microvasculature, including minor vascular invasion and microscopic vascular invasion. Microvascular invasion differs from major vascular invasion, which refers to gross invasion of the right or left main branches of the portal or hepatic veins.

microvessel density (MVD): a quantification technique used to assess the number of vessels in a particular tumor specimen using immunohistochemical stains for endothelial markers. High MVD has been found to be associated with poor prognosis in patients with solid tumors.

minimal residual disease (MRD): the low level of tumor cells (eg, after chemotherapy) that can only be detected with highly sensitive molecular methods (eg, polymerase chain reaction) or to molecularly defined relapse after long-term remission.

mismatch repair: one of four major pathways of DNA repair in mammalian cells. Mismatch repair recognizes and corrects errors in DNA replication leading to single base-pair mismatches or insertions/deletions in small repetitive tracts of DNA known as microsatellites.

mismatch repair genes (MMR): genes that recognize and correct errors in DNA replication leading to single base-pair mismatches or insertions/deletions in small repetitive tracts of DNA known as microsatellites.

missense: a change (mutation) in one nucleotide that results in the coding of a different amino acid.

missense mutation: a change (mutation) in one nucleotide that results in the coding of a different amino acid.

MITF (micropthalmia-associated transcription factor): an early marker for melanocyte lineage and essential for normal melanocyte development. It induces transcription of genes important for melanin production, including tyrosinase. Currently, there are contradictory data regarding MITF, both supporting and negating a role in melanomagenesis.

mitogen: a substance able to induce cellular mitosis or cell division.

mixed lymphocyte-peptide culture (MLPC)/tetramer/cloning: a cytotoxic T lymphocyte (CTL) –monitoring approach in which peripheral blood mononuclear cells are incubated with the target antigenic peptide in limiting dilution conditions. Expanded antigen-specific CTLs are then identified by tetramers (tetrameric arrays of soluble class I major histocompatibility complex–peptide complexes) and cloned for further characterization.

ML-IAP (melanoma inhibitor of apoptosis protein): an antagonist of caspases 3, 7, and 9 that has been identified in patients with melanoma. ML-IAP blocks signaling from the death receptor and mitochondrion-based apoptotic pathways. JNK1 also participates in ML-IAP–mediated suppression of cell death, whereas the mitochondrial protein SMAC/DIABLO is a negative regulator. Thus, ML-IAP endows melanoma cells with a survival advantage during tumor progression.

MLH1 (MutL homolog 1): a DNA mismatch repair enzyme. MLH1 is responsible for overall fidelity of DNA replication.

MLL (myeloid/lymphoid or mixed-lineage leukemia): a protein with two DNA-binding motifs, a DNA methyl transferase motif, a bromodomain, and segments of homology with trithorax, in particular in the C-terminal SET domain.

mLST8: a G protein-β–like subunit that independently and specifically interacts with the kinase domain of mammalian target of rapamycin (mTOR) and stabilizes the mTOR-raptor association.

MMP (matrix metalloprotease [metalloproteinases]): member of a family of enzymes (zinc-dependent endoproteinases) that are involved in the degradation of the extracellular matrix. MMPs are involved in both normal and pathologic tissue remodeling, where their selective proteolysis helps to regulate cell growth, angiogenesis, and invasiveness.

MMP12: gene encoding matrix metalloproteinase 12 (also called macrophage elastase). See MMP (matrix metalloprotease [metalloproteinases]).

MMP9: matrix metalloproteinase 9. See MMP (matrix metalloprotease [metalloproteinases]).

MMPIs (matrix metalloproteinase inhibitor): natural proteins or synthesized compounds that inhibit the activity of one or more MMPs.

MMSET: a member of the class of nuclear-receptor binding, SET domain–containing proteins.

MMSET-FGFR3: a translocation t(4;14)(p16;q32) seen in multiple myeloma that results in the fusion of MMSET with FGFR3 (fibroblast growth factor receptor 3). The fusion protein lacks the SET domain. See MMSET.

MMSET/WHSC1: gene coding for the Wolf-Hirschhorn syndrome candidate 1 protein (also known as multiple myeloma SET domain [MMSET]). Ubiquitously expressed in early development, the WHSC1 protein contains four domains present in other proteins implicated in development: a PWWP domain, an HMG box, a SET domain, and a PHD-type zinc finger. The gene is involved in t(4;14)(p16.3;q32) chromosomal translocation found in approximately 15% of patients with multiple myeloma.

modifiable signal-transducing target: efficient and powerful targets that can predict disease outcome and therapy response and that are particularly helpful because of their multisubstrate/ multifunctional signaling cascade modifications.

modified population analysis: statistical analysis that does not use the intention-to-treat analysis (ie, a strategy for analyzing data in which all participants are included in the group to which they were assigned, whether or not they completed the intervention given to the group). Intention-to-treat analysis prevents bias caused by the loss of participants, which may disrupt the baseline equivalence established by random assignment and which may reflect nonadherence to the protocol.

modified RECIST criteria: RECIST criteria amended for hepatocellular carcinoma where measurement of enhancing tumor is taken into account when classifying response.

molecular cytogenetics: cytogenetic studies that probe the molecular makeup of chromosomes. Several techniques have been developed that have advanced the field of molecular cytogenetics, including fluorescent in situ hybridization and array-based comparative genomic hybridization.

molecular interaction network: molecular interactions (eg, protein-protein and protein-DNA) visualized as a network of interactions using software tools that have been developed to visualize and analyze large-scale data. The network is visualized with molecules as nodes and molecular interactions as edges, with force-directed layout algorithms used to visualize the molecular interaction network. Increasingly, Web-based application programs (eg, WebInterViewer, Ingenuity Pathway Analysis) are used to produce molecular interaction networks of good quality, because multiple molecular interaction networks for shared molecules and for interactions shared by all or some of the networks can be searched.

molecular profiling: a discipline that uses a variety of approaches to generate a global view of mRNA, protein patterns, and DNA alterations in various cell types. Thus, molecular profiles of disease processes may be seen as distinct from normal cells, and therapeutic approaches may be tailored on the basis of molecular profiles.

molecular signature: a discipline that uses a variety of approaches to generate a global view of mRNA, protein patterns, and DNA alterations in various cell types. Thus, molecular signatures of disease processes may be seen as distinct from healthy cells, and therapeutic approaches may be tailored on the basis of molecular signature.

monoclonal antibody: an antibody that is secreted from a single clone of an antibody-forming cell. Large quantities of monoclonal antibodies are produced from hybridomas, which are produced by fusing single antibody-forming cells to tumor cells. The process is initiated with initial immunization against a particular antigen, stimulating the production of antibodies targeted to different epitopes of the antigen. Antibody-forming cells are subsequently isolated from the spleen. By fusing each antibody-forming cell to tumor cells, hybridomas can each be generated with a different specificity and targeted against a different epitope of the antigen.

montanide ISA51: an oil-in-water adjuvant that is safely administered in humans. Montanide ISA51 is similar to Incomplete Freund’s Adjuvant.

Monte-Carlo cross validation: a cross validation method in which the partitions are randomly selected hundreds or thousands of times. See cross validation.

MORF (MOZ-related factor): a factor that preferentially acetylates histones H3 and H4 and has an N-terminal transcriptional repression region containing zinc-finger motifs and shows a very close homology to MOZ throughout its length.

MOZ (monocytic leukemia zinc-finger protein): a MYST protein with histone acetyltransferase activity. See MYST.

MRP (multidrug-resistance protein): an integral membrane phosphoglycoprotein resistant to many drugs.

MSH3: gene encoding the human homolog of the bacterial DNA mismatch repair protein MutS.

MTG16: a transcriptional repressor.

MTHFR (methylenetetrahydrofolate reductase): a metabolic enzyme that catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate. This reaction is required for the multistep process that converts the amino acid homocysteine to methionine. Methionine is an essential amino acid for protein synthesis and is also involved in the production of nucleic acids and other compounds. Reduced MTHFR activity increases the amount of folate—specifically 5,10-methylenetetrahydrofolate, which forms a tertiary complex with thymidylate synthase and fluorouracil, enhancing the action of fluorouracil.

mTORC1: complex composed of mammalian target of rapamycin (mTOR), regulatory associated protein of mTOR (raptor), and mLST8/GL. This complex has the classic features of mTOR by functioning as a sensor for nutrients and energy and controlling protein synthesis. The complex is downstream from AKT and phosphorylates S6K1 upon activation.

mTORC2: complex composed of mammalian target of rapamycin (mTOR), rapamycin-insensitive companion of mTOR (rictor), GL, and mSIN1. Phosphorylation of the complex stimulates AKT phosphorylation at a threonine residue that leads to full AKT activation.

MTT assay: a laboratory test that measures cell growth.

MUC-1: a transmembrane-anchored mucin-type glycoprotein. MUC-1 is present on the surface of normal epithelial cells of organs such as the breast, ovary, pancreas, and colon. It is also a tumor marker because it is overexpressed in similar malignant tissues. Structurally, MUC-1 has an extracellular carbohydrate-rich domain, a transmembrane, and a cytoplasmic domain. Human MUC-1, a membrane-bound glycoprotein, is a primary component of the ductal cell surface of normal glandular cells probably involved in intercell adhesion. MUC-1 is overexpressed and aberrantly glycosylated in carcinoma cells, promoting tumor metastases and inducing immune suppression.

MUGA scan (multigated acquisition/angiogram): a noninvasive heart function test that uses a radioactive tracer to delineate the chambers of the heart and major vessels.

Muir-Torre syndrome: an inheritable autosomal-dominant syndrome. The syndrome is caused by a mutation in the mismatch repair genes responsible for hereditary nonpolyposis colon cancer. It is characterized by a combination of sebaceous tumors of the skin and often colon cancer.

multiple imputation: statistical method of accounting for missing data in research data sets. During multiple imputation, several copies of the data are created, with all missing values entered using their known associations with other recorded variables, additionally introducing a random component. The main analysis is then conducted on each copy of the data, and the results are averaged to produce a final result, while accounting for uncertainty related to variations among the imputed data sets. Under certain assumptions, multiple imputation may provide more precise and less biased results than methods that remove participants with missing data from analysis.

multiple training test partitions: multiple subdivisions of the complete set of patient specimens into a training set and a test set. For each subdivision, or partition, a sample is contained either in the training set or the test set but not both. A completely specified classifier is developed in the training set and applied to classify the specimens in the test set. The proportion of incorrect classifications for samples in the test set is determined. The prediction error rate in the test set is averaged over multiple random partitions of the specimens.

multisubstrate/multifunctional PDPK (proline-directed protein kinase): protein kinase containing signal-transducing network amplifications on a wide spectrum of fatal oncogenic factors in patients with cancer that may have great potential to accurately predict cancer progression, disease outcome, and therapy response.

multivariate proportional hazards model: a general method in medical statistics used to analyze the influence of several (patient-specific) covariates on time-to-event end points. No assumption is made concerning the form of the underlying time-to-event curve. The only assumption made is that the effect of the covariates on the hazard rate in the study population is multiplicative and does not change over time.

MUM1 (IRF4): transcriptional factor multiple myeloma 1/interferon regulatory factor 4 protein, expressed in final step of intragerminal center B-cell differentiation and in postgerminal center B cells.

MUM-3: an antigen (recognized by autologous cytotoxic T cells on melanoma cells) that is ubiquitously expressed and is homologous with the RNA helicase gene family.

mutations in FLT3: The FLT3 gene, located at chromosome band 13q12, encodes a membrane-bound protein member of the class III tyrosine kinase receptor family. Receptors belonging to the tyrosine kinase family (eg, epidermal growth factor receptor and platelet-derived growth factor receptor) are activated through the auto- or transphosphorylation of tyrosine residues in the cytoplasmic region of the receptors in an ATP-dependent manner. An internal tandem duplication of FLT3 is one of the most common mutations in normal karyotype acute myeloid leukemia, occurring in approximately 28% to 38% of such patients.

Myb: a proto-oncogene whose protein product is a transcriptional activator. The transcriptional activity of Myb is enhanced by acetylation, which increases its DNA-binding activity. Myb typically regulates the proliferation and differentiation of certain types of cells; improper regulation of or by this protein is associated with oncogenic transformation.

MYBL2: gene encoding for v-myb myeloblastosis viral oncogene homolog (avian) –like 2 protein, which is a member of the Myb family of proteins. The expressed protein, phosphorlyated during the S-phase of the cell cycle by cyclin A/cyclin-dependent kinase, possesses activator and repressor activities. It activates cyclin D1 and the insulin-like growth factor-binding protein 5 genes. See Myb.

MYCN: gene encoding for N-myc.

myeloid-derived suppressor cell: immature myeloid cells that are triggered to proliferate by chronic inflammation. These cells can suppress both innate and adaptive immune responses.

myogenic: pertaining to muscle tissue. Myogenic may be related to formation of muscle tissue, origination from myocytes or muscle tissue, or molecular signals pertinent to muscle tissues.

myogenin: a muscle-specific transcription factor that can induce myogenesis in a variety of cell types in tissue culture. Myogenin is a member of the basic helix-loop-helix gene family.

MYST: a family (named for its original members MOZ, Ybf2/Sas3, Sas2, and Tip60) of histone acetyltransferases (HATs) that are grouped on the basis of their close sequence homology and the occurrence of a particular acetyltransferase homology region of the GNAT superfamily of HATs.

myxedema: a skin and tissue disorder usually resulting from severe prolonged hypothyroidism.

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