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Oncology Glossary

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IAP (inhibitors of apoptosis proteins): proteins that suppress host cell death in response to viral infection. By binding to caspases, IAPs directly inhibit apoptosis. Survivin and XIAP are members of this family, differing perhaps in binding to selective caspases.

ibrutinib: an irreversible BTK inhibitor.

I-CAM (intercellular cell adhesion molecule): a member of the superfamily of immunoglobulin-like molecules. I-CAM may be expressed on activated endothelial cells and leukocytes. These are target ligands for the integrins expressed by WBCs (heterophilic binding).

Id proteins: a family of proteins identified as inhibitors of differentiation or DNA binding. Id proteins form inactive heterodimers with basic helix-loop-helix (a structural motif in some proteins) transcriptional factors, thus inhibiting transcription.

IDH1 (isocitrate dehydrogenase 1): gene encoding isocitrate dehydrogenase 1. IDH1 converts isocitrate to alpha-ketoglutarate in the cytoplasm. IDH1 mutations in cancer result in a novel enzymatic activity whereby alpha-ketoglutarate is converted to D-2 hydroxyglutarate (R-2 hydroxyglutarate).

idiotype: the unique amino acid sequences in the variable regions of the heavy and light chains of an immunoglobulin molecule.

IDO (indolamine 2,3 dioxygenase): a tryptophan-catabolizing enzyme. IDO is induced by the T-helper 1 cells and cytokine interferon-γ. T lymphocytes undergo proliferation arrest when exposed to tryptophan shortage, which can be provoked by IDO, an enzyme that is expressed in placenta and catalyzes tryptophan degradation. Most human tumors constitutively express IDO.

IFN-α (interferon alfa): a cytokine with multiple postulated mechanisms that is used as antitumor therapy in several diseases, including metastatic renal cell carcinoma and hairy cell leukemia.

IFN-α-2b (interferon alfa-2b): recombinant interferon alfa that is commercially prepared from a bacterial fermentation of E. coli bearing an expression vector containing the interferon alfa-2b (IFN-α-2b) gene from human leukocytes.

IFN-γ (interferon gamma): cytokine that is produced by activated T cells and natural killer cells. The primary action of IFN-γ is the activation of macrophages.

IGF (insulin-like growth factor): proteins with sequences similar to insulin. IGFs trigger similar cellular responses as insulin, including mitogenesis. IGF-1 (secreted by the liver) and IGF-2 (secreted by brain, kidney, pancreas, and muscle) function through cell surface receptors. See IGF-1R.

IGF-1 (insulin-like growth factor-I): see IGF (insulin-like growth factor).

IGF-1R (insulin-like growth factor-1 receptor): a tyrosine kinase receptor that protects several cell types from apoptotic injuries by way of the activation of PI3K, Akt/PKB, and phosphorylation of BAD (leading to its inactivation). IGF-1R also mediates regulation of angiogenic factors in tumor cells.

IGF-2R: also called the IGF-2R/M6P. IGF-2R is functionally different from IGF-1R. The receptor has an extracellular domain that binds M6P and IGF-2. The receptor also binds lysosomal enzymes. IGF-2R/M6P may be involved in clearing IGF-2 from circulation by endocytosis. The receptor has also been shown to bind to retinoic acid and urokinase-type plasminogen activator receptor at different sites. Intracellular IGF-2R/M6P functions to direct lysosomal enzymes to lysosomes. In addition, IGF-2R/M6P has been shown to be death receptor for granzyme B during cytotoxic T-cell–induced apoptosis.

IGFBP-3 (insulin-like growth factor binding protein-3): a member of the family of high-affinity proteins. IGFBP-3 influences cell proliferation by modulating access of IGFs to the IGF receptors. IGFBP-3 is known to inhibit cell growth by sequestering IGFs and induces apoptosis in an IGF-independent manner. In some circumstances, IGFBP3 can have an opposite effect, because it acts as a carrier of IGFs toward its receptor, thus supporting the proliferative effect of this growth factor.

IGFBPs (IGF-binding proteins): a family of six conserved proteins that share the ability to bind the insulin-like growth factors IGF-1 and IGF-2. They are secreted proteins and are found in serum, all biologic fluids, and tissue extracts. The amino and carboxy termini of the members belonging to this family show sequence similarity, with variability present in the central region of the molecules. IGFBPs function by binding to IGFs and inhibit interactions of IGFs with their receptors, IGF-1R and IGF-2R. The roles of different IGFBPs may differ depending on their tissue expression, regulation by hormones and growth factors, proteolytic degradation, and association with cell membranes or cell membrane receptors. Some IGFBPs have nuclear localization signals and may be found within the nucleus.

IGHV mutation status: the immunoglobulin heavy chain variable region genes at the B-cell receptor locus. This gene locus is the target of a high rate of somatic mutations (termed somatic hypermutation) during proliferation of B cells upon antigen stimulation and recognition. In chronic lymphocytic leukemia, IGHV mutation status is clinically relevant because it is highly correlated with disease prognosis and outcome. Patients with chronic lymphocytic leukemia with mutated IGHV locus (typically exhibiting 98% sequence homology to germline) generally have a more favorable clinical outcome.

I-κB: inhibitor of NF-κB. See NF-κB.

IκK (IκB kinase): a complex of two subunits, IκKα and IκKβ. IκB-kinase directly phosphorylates IκB in complex with NFκB. The phosphorylation leads to the dissociation of IκB from NF-κB, an event responsible for the activation of NF-κB. Phosphorylated IκB is targeted for degradation.

Ileal conduit: a form of urostomy that involves anastomosing the ureters to a detached segment of ileum and the other end of the ileum is brought out on the abdominal wall as a stoma.

ILK (integrin-linked kinase): a serine/threonine kinase with ankyrin-like repeats. ILK regulates transduction of extracellular matrix signaling through integrins by interacting with the cytoplasmic domain of beta-1 and beta-3 integrins. ILK links integrins and growth factor receptors to the actin cytoskeleton, where it facilitates interaction with several proteins. It phosphorylates a variety of substrates, including Akt (important in survival pathways), β-1 integrin, and glycogen synthase kinase.

ILT: a family of genes encoding immunoglobulin-like transcripts. A subset of ILTs (ILT2, ILT3, ILT4, ILT5, and leukocyte immunoglobulin-like receptor 8) displays long cytoplasmic tails, which have immunoreceptor tyrosine-based inhibitory motifs. A second subset (ILT1, ILT7, ILT8, and leukocyte immunoglobulin-like receptor 6) contains short cytoplasmic domains lacking signal transduction motifs but having basic arginine residue within the transmembrane domain, which associates with the FcR γ-chain and transduces stimulatory signals.

IM862: a synthetic dipeptide (l-glutamine l-tryptophan). IM862 was isolated from bovine thymus and has been used as an adjuvant treatment to chemotherapy in parasitic and fungal disorders. It has been shown to be an inhibitor of angiogenesis in several assays that monitor angiogenesis.

image-guided radiation therapy: a technique of radiation therapy delivery in which the location of the tumor is monitored by imaging on a daily basis to ensure the precise delivery of the radiation therapy dose to the predefined volume of interest.

imatinib: a small molecule compound originally developed for treating chronic myelogenous leukemia and GI stromal tumors. Imatinib (STI571; Gleevec, Novartis, East Hanover, NJ) is a selective tyrosine kinase inhibitor that binds to the ATP-binding pocket and blocks the tyrosine kinase activities of Abl, c-kit, and platelet-derived growth factor receptor.

immune checkpoint: immune inhibitory pathway that negatively modulates the duration and amplitude of immune responses. Examples include the CTLA-4:B7.1/B7.2 pathway, and the PD-1:PD-L1/PD-L2 pathway.

immunity: resistance to invasion by a specific pathogen.

immunoblotting: probing for cellular proteins blotted onto a nylon membrane using antibodies specific to the protein of interest. Cellular proteins are first separated on the basis of molecular weights using gel electrophoresis. The proteins from the gel are then transferred on to a nylon membrane either by diffusion or using an electric field. The cellular proteins on the gel are probed with the primary antibody specific to the protein of interest. The antigen-antibody complex is then detected using a secondary detection system.

immunochemotherapy: a combination of immunotherapy (eg, anti-CD20) and chemotherapy.

immunoescape: a general term referring to the many efforts by tumor cells to suppress or evade antitumor immunity. This may lead to upregulation of inhibitory proteins or downregulation of required proteins necessary for efficient antitumor immunity.

immunofluorescence: laboratory methods that combine the use of antibody reagents to detect the presence of specific biomolecule antigens in situ with a detection system that uses fluorescent molecules to visualize the localization of the target antigen/antibody complex.

immunogenic: capable of inducing an immune response.

immunoglobulin: a class of proteins produced in lymph tissue.

immunoglobulin H VDJ region: a unique region in the immunoglobulin heavy (IgH) chain that connects the variable (V) region of the molecule with the constant region. Briefly, the genetic locus that comprises IgH is made up of heavy chain V genes, heavy chain diversity (D) segments, heavy chain joining (J) segments, and heavy chain constant (C) regions. B-cell development results in changes at the IgH locus that involve DNA rearrangements. VDJ joining occurs at the pro–B-cell stage, prior to activation of V genes. Class switching occurs later in B-cell development. Ultimately, unique combinations of V, D, J, and C segments result in the expression of unique heavy chains.

immunoglobulin heavy (IgH) chain genes: the genetic locus that comprises the IgH chain genes, which is made up of heavy chain variable (V) genes, heavy chain diversity (D) segments, heavy chain joining (J) segments, and heavy chain constant (C) regions. B-cell development results in changes at the IgH locus that involve DNA rearrangements. VDJ joining occurs at the pro–B-cell stage, prior to activation of V genes. Class switching occurs later in B-cell development. Ultimately, unique combinations of V, D, J, and C segments result in the expression of unique heavy chains.

immunoglobulin isotype: the different constant regions of the heavy and light chains of the immunoglobulin. On the basis of the constant region of the heavy chain, the isotype of the immunoglobulin may be IgM, IgG, IgA, IgD, or IgE. On the basis of the constant region of the light chain, the isotype of the immunoglobulin may be either kappa or lambda.

immunohistochemical analyses: techniques used to evaluate the levels and patterns of expression of protein on cells or tissue specimens located on flat slides.

immunohistochemistry: the application of antigen-antibody interactions to histochemical techniques. Typically, a tissue section is mounted on a slide and incubated with antibodies (polyclonal or monoclonal) specific to the antigen (primary reaction). The antigen-antibody signal is then amplified using a second antibody conjugated to a complex of peroxidase-antiperoxidase, avidin-biotin-peroxidase, or avidin-biotin alkaline phosphatase. In the presence of substrate and chromogen, the enzyme forms a colored deposit at the sites of antibody-antigen binding. Immunofluorescence is an alternate approach to visualize antigens. In this technique, the primary antigen-antibody signal is amplified using a second antibody conjugated to a fluorochrome. On ultraviolet light absorption, the fluorochrome emits its own light at a longer wavelength (fluorescence), thus allowing localization of antibody-antigen complexes.

immunophenotyping: a method to identify cells on the basis of their surface antigens. This assay, applying a panel of different fluorochrome-conjugated antibodies, is used to diagnose specific types of leukemia and lymphoma.

immunoscintigraphy: an imaging scintigraphic procedure that uses a radiolabeled antibody as the radiopharmaceutical for the detection of an antigen expressed by a lesion.

immunosuppressive: a substance that lowers the body’s normal immune response.

immunotherapy: a therapeutic approach that uses cellular and/or humoral elements of the immune system to fight a disease.

immunotoxin: a molecule containing an antibody or antibody fragment connected to a protein toxin. Immunotoxins bind to cell-surface antigens via the antibody domain, and after being internalized into the cell, the toxin mediates catalytic cell death. Recombinant immunotoxins refer to proteins in which the Fv is linked to the toxin by a peptide.

importin-α7: protein responsible for importing substrates across the nuclear membrane.

imputation: in a genome-wide association study, the use of a reference data set (eg, HapMaP) and linkage disequilibrium in a region to infer the alleles of single nucleotide polymorphisms not directly genotyped.

in situ hybridization: a method used to detect specific gene sequences in tissue sections or cell preparations by hybridizing the complementary strand of a nucleotide probe to the sequence of interest.

in vitro fertilization (IVF): a procedure in which fertilization occurs outside of the body. The embryos are either placed in a woman’s uterus or stored for future use.

incremental cost-effectiveness ratio (ICER): an equation used commonly in health economics to provide a practical approach to decision making regarding health interventions. It is typically used in cost-effectiveness analysis. ICER is the ratio of the change in costs to incremental benefits of a therapeutic intervention or treatment.

individual-level surrogacy: the association between the true and the surrogate end points at the level of the individual patient, after adjusting for the treatment effect.

indolin-2-one structural analogues: 3-substituted indolin-2-one analogues were designed and synthesized as a novel class of tyrosine kinase inhibitors which exhibit selectivity toward different receptor tyrosine kinases.

inflammatory breast cancer: a clinical diagnosis characterized by rapid enlargement of the breast, generalized induration in the presence or absence of a distinct breast mass, edema of the skin of the breast, erythema that must involve more than one third of the breast, and biopsy-proven carcinoma.

influenza virosome: composed of the influenza surface glycoproteins hemagglutinin and neuraminidase and a mixture of natural and synthetic phospholipids. The virosome delivery system can present a wide variety of antigens to the immune system, including recombinant proteins, synthetic peptides, and bacterial toxins. Virosomes retain the fusogenic properties of the influenza virus, facilitating binding and endocytosis of any incorporated antigen into immunocompetent cells, initiating an efficient immune response.

innate immunity: a nonspecific immune response the body has to any foreign stimulus. This type of immunity is not specific to any particular antigen, and no immunologic memory is generated.

insertion/deletion (indel): a local net gain or loss of nucleotides (generally, between one and 50 bases) that results in a frameshift event.

insulin-like growth factor (IGF) axis: a hierarchy of proteins that work together to regulate the amount of free, biologically active IGF available to interact with target cells. This hierarchy includes growth hormone, insulin-like growth factor-I (IGF-I), insulin-like growth factor-II (IGF-II), six IGF binding proteins (IGFBP), and IGFBP proteases.

integrated optical density (IOD): a computer-assisted method usually used to quantify both the area and the intensity of the positive staining of immunohistochemistry.

integrins: cell-adhesion receptors that are involved in two important pathways: cell-extracellular matrix and cell-cell interactions, thus allowing for cell-cell and cell-extracellular matrix communication. Functionally, integrins are composed of two subunits (heterodimers), one belonging to the α family and the other belonging to the β family.

intensity-modulated radiation therapy: radiation treatment using beams with nonuniform fluence profiles that shape the dose distribution in the target volume and adjacent normal structures. Beam modulation is typically achieved via multileaf collimators or custom-milled compensators to achieve the appropriate fluence profiles calculated by inverse optimization algorithms. The radiation beam is divided into beamlets of varying intensity such that the sum from multiple beams via inverse planning results in improved tumor targeting and normal tissue sparing. A technique of radiation therapy delivery in which the intensity of each beamlet of radiation coming from a specific angle can be adjusted to provide a desired dose distribution when the doses delivered from all beamlets are added from a single angle and from all dose delivery angles. An advanced type of high-precision radiation therapy, which aims to improve the coverage of the radiation therapy target and/or minimize radiation dose to surrounding normal tissue.

interleukin-1 (IL-1): produced by activated macrophages, endothelial cells, and B cells. IL-1 is a cytokine that induces inflammatory responses. As a proinflammatory cytokine, IL-1 has a role in immune, degradative, and growth-promoting processes. Belonging to this class of cytokines, IL-1β and IL-1α are agonists whereas IL-1Ra is an antagonist of the IL-1 receptor.

interleukin-11 (IL-11): a pleiotropic cytokine with diverse biologic activities on several cell types. In general, IL-11 modulates inflammatory processes. It also stimulates T-cell–dependent development of immunoglobulin, proliferation of hematopoietic stem cells, osteoclastic activity in bone, and decidualization of endometrium.

interleukin-1β (IL-1β): see interleukin-1 (IL-1).

interleukin-2 (IL-2): a cytokine that stimulates proliferation of activated T cells and, at high doses, is used as antitumor therapy in metastatic renal cell carcinoma.

interleukin-4 (IL-4): a cytokine that is responsible for B-cell differentiation, activation, proliferation, and immunoglobulin E switch. IL-4 is produced by T cells, mast cells, and basophils. It functions through the CD124 receptor.

interleukin-6 (IL-6): produced predominantly by activated immune cells such as microglia. IL-6 is involved in the amplification of inflammatory reactions.

interleukin-8 (IL-8): a proinflammatory cytokine structurally related to platelet factor 4. IL-8 is released by several cell types (eg, monocytes, macrophages, T cells, endothelial cells, tumor cells) in response to an inflammatory stimulus. It activates neutrophils and is a chemokine for neutrophils and T lymphocytes. It is also an angiogenic factor.

internal validation: estimation of the predictive accuracy of a model in the same study used to develop the model. Typically, the sample is split in two portions, one used as a training set in the model, and the other is reserved for testing the model. The internal estimate of predictive accuracy should be used to provide a preliminary measure of the predictive power of the variables used. Developmental studies often do not adequately represent real-world conditions of therapeutic decision making, and hence external validation of the clinical value of the classifier is required.

International Germ Cell Cancer Collaborative Group classification: a classification for metastatic germ cell cancer which is based on prognostic factors including site of the primary tumor, presence or absence of nonpulmonary visceral metastases, and the level of tumor marker AFP, HCG, and LDH.

International Prostate Symptom Scores (IPSS): an eight-question (seven symptom questions plus one quality-of-life question) written screening tool used to diagnose and track urinary symptoms that also has been related to outcome after some types of prostate cancer treatment.

interstitial fluid pressure: the pressure exerted by the free interstitial fluid in a tissue, which is nearly zero mmHg in most normal tissues but much higher in tumors, because of leaky blood vessels. Interstitial fluid pressure cannot permanently collapse leak vessels.

intrinsic genes: a set of genes whose level of expression is used to sort breast cancers into subtypes.

intrinsic subtype: a subset of tumors that share similarities in their gene expression profile. Subtypes are identified by unsupervised analysis of gene expression.

irinotecan: a plant alkaloid. A prodrug is converted to a biologically active metabolite 7-ethyl-10-hydroxy-camptothecin (SN-38) by a carboxylesterase-converting enzyme. SN-38 inhibits topoisomerase I activity.

IRS1: gene encoding insulin receptor substrate 1. It mediates the biologic response to insulin stimulation by binding and activating various enzymes or adaptor molecules.

ISG20: gene encoding for the exonuclease protein ISG20, which is stimulated by interferon and is directly induced by synthetic double-stranded RNA via NF-κB and IRK-1 activation.

ISIS 2503: a phosphorothioate antisense oligodeoxynucleotide designed to hybridize to the 3'-untranslated region of human H-Ras mRNA.

ISIS 5132: an antisense oligonucletide targeting the mRNA for c-Raf.

isobologram: a means of graphically displaying drug interactions.

isoforms: proteins derived from the same gene but have distinct physical, and sometimes biologic, properties, arising from a differential exon-splicing process.

ISWI: an ATPase that has sequence similarity to the Swi/Snf homolog in Drosophila, the name implies imitation switch.

ITGβ7: gene coding for integrin β7. See integrins.

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