Oncology Flashcards

Question

multi-drug resistance (MDR)

Answer 1

mediated by ATP-depended drug efflux pumps; common genes include P-glycoprotein (PgP, MDR1), multi-drug resistance proteins (MRP1, 2, 3, 6, 7); especially big issue for vinca alkaloids, doxorubicin, bleomycin, etoposide, paclitaxel

Answer 2

simultaneous action of two inhibitors acting on different steps of a linear metabolic pathway (i.e. hydroxyurea + cytarabine, methotrexate + 5-FU)

Answer 3

inhibitors that block two separate pathways which lead to the same end product

Answer 4

use of one drug that affects the function of an end product and another drug that affects the synthesis of that end product (i.e. cytarabine + doxorubicin)

Answer 5

"rescue" of the patient's normal cells from chemotherapy; i.e., methotrexate + leucovorin or autologous bone marrow/stem cell transplant

Answer 6

inducing cells to enter one phase of the cell cycle, then using a drug that is specific for that phase (i.e., low-dose 5-FU to block in S-phase, then high-dose cytarabine to kill in S-phase)

Answer 7

bring cells out of G0 and back into cell cycle; first treat with cell cycle nonspecific drugs (i.e. mechlorethamine or carmustine), then treat with cell cycle-specific drugs

Answer 8

a measure of the presence of activated T-cells in and at the margins of a tumor; presence of more T-cells is prognostic of better survival

Answer 9

treatment of a tumor by injection of ex vivo-expanded tumor-experienced T-cells

Answer 10

produced by dendritic cells, activates NK cells

Answer 11

produced by Th1 cells, promotes T-cell survival and proliferation

Answer 12

enzyme expressed by many tumors; converts L-tryptopha to N-formylkynurenine, an immunosuppressive molecule; allows a tumor to suppress host anti-tumor immune responses

Answer 13

enzyme expressed by many tumors; breaks down/depletes arginine, which is required for T-cell activation and survival; allows a tumor to suppress host anti-tumor immune responses

Answer 14

enzyme expressed by many tumors; produces reactive oxygen and nitrogen species, which may nitrocylate TCRs and inhibit their efficacy; allows a tumor to suppress host anti-tumor immune responses

Answer 15

an abnormal mass of tissue, the growth of which exceed and is uncoordinated with that of the normal tissues and persists in the same excessive manner after cessation of the stimuli which evoked the change

Answer 16

a tumor that resembles normal tissue, grows slowly, is non-invasive/encapsulated/well-demarcated, and does not metastasized; named with suffix "-oma"

Answer 17

a tumor of variable morphology, variable growth rate (generally faster than normal tissue), has an invasive growth pattern, and is capable of metastasizing; cancer; named as a carcinoma or sarcoma

Answer 18

swelling; often used interchangeably with "neoplasia"

Answer 19

tissues that cover surfaces, tubules, and ducts; tumors that originate in this tissue are termed carcinomas

Answer 20

connective tissues; tumors that originate in this tissue are termed sarcomas

Answer 21

extent to which tumor cells morphologically and functionally resemble the normal tissue counterpart

Answer 22

cancer originating in epithelial tissue

Answer 23

cancer originating in mesenchymal tissue

Answer 24

benign tumor

Answer 25

prefix describing a tumor originating in fibroblasts

Answer 26

anti-inflammatory cytokine produced by M2 macrophages (often induced by tumor cytokines)

Answer 27

released by macrophages, may induce chronic inflammation

Answer 28

immunosuppressive signaling molecule produced by many tumors

Answer 29

immunosuppressive receptor found on activated T-cells that, when engaged with ligand B7, induces T-cell suppression/apoptosis; in normal immune response, facilitates downregulation of activated T-cells to prevent autoimmunity

Answer 30

immunosuppressive receptor found on T-cells; when engaged with ligand, is a negative signal for T-cell activation

Answer 31

immunosuppressive ligand for PD-1 that is upregulated on many tumor cells; inhibits T-cell activation through engagement with PD-1

Answer 32

released by macrophages, may induce chronic inflammation

Answer 33

a particular granulocyte(includes PMNs) or macrophage phenotype that is the major driver of an immunosuppressive tumor microenvironment; may secrete IDO, organize, IL-10, TGF-beta, PGE2, etc.

Answer 34

macrophage found in the tumor microenvironment; may be induced by the tumor into a myeloid suppressor cell phenotype

Answer 35

released by macrophages, may induce chronic inflammation; also released by many tumors, may nitrocylate TCRs

Answer 36

produced by delta-gamma T-cells and NK cells, induces dendritic cell activation and maturation

Answer 37

produced by delta-gamma T-cells

Answer 38

produced by Th2 cells, immunosuppressive in the tumor microenvironment

Answer 39

produced by Th2 cells, immunosuppressive in the tumor microenvironment

Answer 40

growth factor critical for tumor angiogenesis; antagonized by bevacizumab (Avastin)

Answer 41

receptor for epithelial growth factor often targeted in cancer treatment by trastuzumab (Herceptin)

Answer 42

prefix describing a tumor originating in adipocytes

Answer 43

prefix describing a tumor originating in smooth muscle cells

Answer 44

prefix describing a tumor originating in skeletal muscle cells

Answer 45

prefix describing a tumor originating in bone tissue

Answer 46

prefix describing a tumor originating in cartilage

Answer 47

prefix describing a tumor originating in blood vessels

Answer 48

a tumor with multiple morphological components; both epithelial and mesenchymal origin

Answer 49

predominantly benign tumors; originate from totipotent stem cells, composed of tissue derived from multiple germ layers

Answer 50

mixed tumor of both epithelial and mesenchymal cell origin

Answer 51

a mass of disorganized, mature tissue that is specific to the site of development; indicative of anomalous development (common in stomach, lung)

Answer 52

a mass of ectopic tissue in a foreign location; i.e., gastric heterotopia (island of gastric mucosa in the colon)

Answer 53

anti-CTLA-4 mAb often used in cancer treatment to enhance host immune response against tumor cells/block T-cell inactivation by tumor cells; more toxicity than pembrolizumab

Answer 54

anti-PD-1 mAb used in cancer treatment to enhance host immune response against tumor cells/block T-cell suppression by tumor cells

Answer 55

anti-PD-1 mAb often used in cancer treatment to enhance host immune response against tumor cells/block T-cell suppression by tumor cells; less toxicity than ipilimumab

Answer 56

mediated by NK cells via CD16 recognition of IgG Fc domains/IgG specificity for tumor cell antigens; also mediated by macrophages and T-cells; stimulated by administration of mAbs in cancer treatment

Answer 57

a genetically-engineered receptor often introduced into TILs for adoptive cell transfer that has both an antibody component that is specific for a particular tumor cell antigen as well as a TCR signaling component that is connected to T-cell activation pathways; induces all T-cells in culture to be specific for that cancer antigen (in addition to their native antigens); only effective in hematologic cancers

Answer 58

T-cells isolated and cultured from a patient's tumor that has been surgically resected, which are then activated and expanded using a cytokine mix and reinfused into the patient following conditioning (via chemotherapy or radiation)

Answer 59

experimental method of using tumor cells, allogeneic tumor cells, genetically modified APCs, or cancer antigens/proteins in order to vaccinate a patient against cancer cells

Answer 60

transplantation of donor hematopoietic stem cells, sometimes along with donor T-cells, in order to replace cancerous blood cells; when T-cells are included, they may react against host antigens, which may cause GVHD or may also attack residual host tumor cells

Answer 61

when donor T-cells are included in an HSCT and allowed to react against host cells so that they can kill residual tumor cells; often induces complete remission

Answer 62

a system of rating a tumor to indicate how much it resembles normal tissue; cellular metrics include cellular/nuclear pleomorphism, coarsely-clumped chromatin, hyperchromatic nuclei, high nuclear to cytoplasmic ratio, large nucleoli, atypical/bizarre mitoses, loss of tissue polarity, and tumor giant cells

Answer 63

complete lack of tissue differentiation; describes a tumor that lacks any resemblance to parent tissue; can make it difficult to determine tissue origin of metastases

Answer 64

when a tumor has penetrated the basement membrane and invaded the extracellular matrix; involves loss of E-cadherin function, degradation of basement membrane via MMPs, change of attachments (loss of interns), and migration

Answer 65

migration of malignant cells to tissues/organs outside their parent tissue; common sites of metastasis include lymph nodes, lungs, liver, bone, and brain; each tumor type has a penchant for specific metastatic sites based on adhesion molecules and chemokines expressed

Answer 66

malignant/dysplastic epithelial tissue characterized by full-thickness dysplasia that has not yet invaded its basement membrane

Answer 67

disordered growth, i.e. loss of polarity, loss of maturation, loss of architecture, loss of organization

Answer 68

the first lymph node to receive drainage from the site of a tumor; useful to resect and stain to look for first metastases (particularly in carcinomas)

Answer 69

describes the severity of a cancer, including the magnitude/size of the primary tumor and the extent of spread in the body; TNM staging includes tumor size, nodal involvement, and metastasis; metrics are combined to determine "overall" stage of I, II, III, or IV

Answer 70

systemic syndromes due to non-hormonal (hypercoagulability, cytokines, etc.) or hormonal effects of a tumor; examples include Cushing syndrome, hypercalcemia, nonbacterial thrombotic endocarditis, and carcinoid syndrome

Answer 71

cancer of bone or soft tissue; common in adolescents and young adults; caused by translocation between chromosomes 11 (FLI1 gene) and 22 (EWS gene); Dx via histology, immunohistochemistry, molecular cytogenetics

Answer 72

associated with HIV+ individuals; involves interaction between human herpes virus 8 (HHV-8), inflammatory cytokines, and angiogenic factors in the context of profound immune suppression

Answer 73

angi-VEGF drug that, when injected directly into the vitreous humor of the eye, antagonizes VEGF and not only blocks wet AMD progression but also restores lost vision and reduces vascularity

Answer 74

angi-VEGF drug that, when injected directly into the vitreous humor of the eye, antagonizes VEGF and not only blocks wet AMD progression but also restores lost vision and reduces vascularity

Answer 75

specialized highly-polarized endothelial cell that begins process of angiogenesis; resembles a sprouting axon, has many filopodia that sense the surrounding environment; induced by VEGF-A signaling/VEGFR2 on filopodia, receives low notch signal, upregulates Kdr, Nrp, and Flt4; forms through loosening cell junctions (VE-cadherin), matrix remodeling (MMPs), angiogenic factors (VEGF, FGFs, ANG-2, cheekiness

Answer 76

endothelial cells that work in concert with a single tip cell to promote angiogenesis; differentiate in response to VEGF-A/VEGFR1 and receiving notch signaling, repress Kdr, Nrp, and Flt4 while expressing sFlt1; proliferate when stimulated with VEGF-A, establish firm adherens junctions, deposit basement membrane, express axon-guidance genes (Robo4, Jag1, Flt1)

Answer 77

family of membrane-bound receptors that are stimulated by membrane-bound ligands (cell contact-dependent signaling); signaling involves internalization of the extracellular domain of notch into the signal-sending cell followed by cleavage of the intracellular domain by the signal-receiving cell, which alters gene expression in the signal-receiving cell; during angiogenesis, endothelial cell stimulation by VEGFA stimulates expression of the notch ligand DII4, which allows bilateral notch signaling/competition for tip cell differentiation; ultimately the tip cell expresses VEGFR2 and becomes the signal-sending cell for notch, while the stalk cells express VEGFR1 and become the signal-receiving cells for notch signaling

Answer 78

disease of pathologic angiogenesis taking place in the retina, leading to degenerative disease and vision loss

Answer 79

found on chromosome 9, codes for non-receptor tyrosine kinase; constitutively active when translocated to BCR locus on chromosome 22 (t(9;22) Philadelphia chromosome), common in CML and ALL, treatable with imatinib

Answer 80

a normal gene with tightly-regulated expression that usually regulates cell growth; may encode genes such as growth factors, growth factor receptors, signal transducers, transcription factors, or cell cycle regulators; gain-of-function mutations may cause transformation into an oncogene

Answer 81

viruses that directly induce malignant phenotypes, either through viral genomic integration (leads to over-expression of viral proteins that affect cell growth or disruption of a proto-oncogene) or stimulation of host inflammatory responses with subsequent regeneration (i.e., hepatitis B/C, H. pylori, etc.); examples include EBV (LMP1 oncoprotein stimulates JAK2/STAT pathway and activates Bcl-2, EBNA2 stimulates cyclin D1)

Answer 82

a chemical that causes permanent DNA mutations (may be direct or indirect); mutations only truly permanent if they are propagated (i.e., not repaired before the cell divides)

Answer 83

a nontumorigenic chemical that reversibly enhances the proliferation of mutated cells; i.e., phorbol esters, hormones, phenols, bile salts, alcohol

Answer 84

transcription factor that, under hypoxic conditions, drives expression of angiogenic and proliferative genes; under normoxic conditions, it is hydroxylated by prolyl-hydroxylase and targeted for ubiquitinization by VHL

Answer 85

von Hippel-Lindau protein; under normoxic conditions, targets HIF-1alpha for destruction to prevent pathogenic angiogenesis

Answer 86

inherited loss-of-function mutation in VHL gene, causes increased frequency of hemangioblastomas in the retina and CNS

Answer 87

multi-modal: surgery, radiation, chemotherapy

Answer 88

drugs used as one part of cancer treatment that are intended to kill all tumor cells, spare normal cells, and increase the host capacity to fight cancer; ideal drugs are nontoxic to normal cells, kill all tumor cells, have a broad spectrum of activity, good distribution in the body, adequate half-life, non-immunogenic, low incidence of side effects, low cost, oral dosing

Answer 89

aim for 2-log kill and 4-12 cycles of therapy; constant dose of drug kills a constant fraction of tumor cells; tumor size correlates to duration of therapy, NOT dose

Answer 90

time required for one cell to become two cells

Answer 91

mutated proto-oncogenes with dysregulated, autonomous function/constitutive expression that cause unregulated cell proliferation; usually require gain-of-function mutation on only one allele (dominant)

Answer 92

master regulator transcription factor for cell growth found on chromosome 8 that induces expression of cyclin D, rRNA genes, metabolic reprogramming/Warburg effect, and telomerase; can also reprogram somatic cells into pluripotent stem cells; also inhibits growth-suppressing genes, such as CDKI; when translocated to IG gene locus on chromosome 14 (Ig heavy chain promotor) induces Burkitt's lymphoma

Answer 93

cell cycle regulatory proteins; cyclins are transiently-expressed, unstable proteins that activate CDKs, while CDKs are constitutively-expressed enzymes that phosphorylate target proteins

Answer 94

activated by CDK4, phosphorylates RB to allow the cell to pass through the G1 restriction checkpoint; when fused to IgH gene due to d(11;14) causes mantle cell lymphoma; also in plasma cell myeloma and hairy cell leukemias

Answer 95

APC normally sequesters and mediates destruction/down-regulation of beta-catenin, which is a transcription factor for various growth factors; loss-of-function mutations in APC lead to beta-catenin accumulation and complexing with TCF, which leads to transcription and unregulated cell growth; causes familial adenomatous polyposis (FAP), requires prophylactic colectomy (affects colon more than other organs)

Answer 96

tumor-suppressor gene; "guardian of the genome;" senses cellular stress, such as anoxia, DNA damage, oncoprotein activity, and directs cells to enter repair, senescence, or apoptosis; mediators include p21, GADD45, and BAX; regulated by Mdm2, which ordinarily promotes ubiquitinization of p53, but cellular stress induces phosphorylation of Mdm2/liberation of p53, which is subsequently acetylated (by ATM/ATR family) and acts as a transcription factor

Answer 97

protein that antagonizes apoptosis/stabilizes mitochondrial membrane to prevent cytochrome c leakage; neutralized by BH3; overexpressed in many lymphomas, particularly follicular lymphoma (lack of normal apoptosis in germinal center)

Answer 98

p53 mediator, induces cells to enter apoptosis

Answer 99

highly reactive electron-deificent compounds that react with electron-rich sites (such as DNA, RNA, protein, etc.) and do not require enzymatic processing, i.e. alkylating agents

Answer 100

compounds that require metabolism by CYP450 systems to become carcinogenic

Answer 101

genes that control cell growth; loss-of-function recessive mutations lead to mutator phenotypes/cancer

Answer 102

apoptosis-inhibiting genes; includes Bcl-2, IAP

Answer 103

apoptosis-promoting genes; includes Fas (CD95)/FasL, FLICE death complex, procaspase 8/3, cytochrome c, BAX/BAK, APAF-1, BH3

Answer 104

often upregulated in breast carcinomas, poor prognostic sign (predicts lack of responsiveness to estrogen therapy); treatable with trastuzumab, an anti-Her2 mAb

Answer 105

mutation common in gastrointestinal stream tumors; codes for receptor tyrosine kinase, mutation causes upregulation; treatable with imatinib (Gleevec)

Answer 106

pro-growth signal transducing protein, mutated oncogene is constitutively active and does not require receptor stimulation; mutations commonly affect GTP binding or GTP hydrolysis

Answer 107

most commonly-mutated gene in AML (30% of cases); good prognostic indicator, typically includes a 4bp insertion

Answer 108

codes for serine/threonine protein kinase, mutations found in all hairy cell leukemia, also common in colon cancer, melanomas, and benign nevi; treatable with vemurafenib and dabrafenib

Answer 109

codes for lipid kinase, mutations in the catalytic subunit lead to increased enzyme activity and are found in various cancer; PI3K is negatively regulated by PTEN

Answer 110

encodes p16 and ARF; inhibits Cyclin D/CDK4 complex, promotes RB-mediated cell cycle inhibition

Answer 111

inherited p53 mutation, endows a risk of developing cancer by 50 y.o. that is 25X higher than average; characterized by a wide variety of cancers at younger ages and multiple cancers in the same individual

Answer 112

caused by mutations in mismatch repair genes, induces a mutator phenotype and micro satellite instability; individuals have much higher risk of cancer

Answer 113

gene families that have at least one receptor and one ligand in both neural and vascular tissue; includes Netrin, Sema3, Slit, and Ephrin