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Immunology > Malignancies > Flashcards

Malignancies Flashcards

1
Q

RAS activates this pathway

A

PI3K pathway

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2
Q

This pathway leads to progrowth metabolism (Warburg)

A

PI3K pathway
Activated by Ras

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3
Q

RAS activates this transcription factor which stimulates production of MYC and cyclins

A

BRAF

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4
Q

BRAF is activated by RAS and induces production of these 2

A

MYC and cyclins

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5
Q

BRAF is activated by Ras and induces production of this, which leads to pro-growth pathways

A

MYC

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6
Q

This is dysregulated in neuroblastoma

A

MYC

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7
Q

Proteins that cause progression through the cell cycle

A

Cyclins

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8
Q

Cyclins attach to and activate these

A

Cyclin dependent kinases (CDKs)

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9
Q

These attach to and activate cyclin dependent kinases (CDKs)

A

cyclins

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10
Q

These phosphorylate various proteins to produce growth, division, metabolic effects
Lose activity when the attached cyclin degrades

A

Cyclin dependent kinases (CDKs)

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11
Q

Two checkpoints in the cell cycle

A

Between G1-S progression and G2-M progression

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12
Q

This cyclin binds CDK4

A

Cyclin D

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13
Q

Cyclin D binds this CDK

A

CDK4

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14
Q

MYC stimulates this cyclin pathway

A

Cyclin D

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15
Q

This stimulates the cyclin D pathway

A

MYC

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16
Q

This is inactivated and allows S phase entry

A

Rb

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17
Q

Tumor suppressor gene that is lost in Familial Retinoblastoma

A

Rb

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18
Q

Translocation in mantle cell lymphoma

A

t(11:14) of cyclin D

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19
Q

Ras may be dysregulated by this type of mutation

A

Gain of function

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20
Q

This inhibits many proto-oncogenes

A

p53

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21
Q

Tumor suppressor gene that inhibits cyclin dependent kinase (CDK4-Cyclin D complex)
Often lost in melanoma

A

p16

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22
Q

p16 inhibits this

A

Cyclin dependent kinase (CDK4-cyclin D complex)

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23
Q

Tumor suppressor gene that is often lost in melanoma

A

p16

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24
Q

PTEN inhibits this

A

PI3K

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25
Q

This inhibits PI3K

A

PTEN

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26
Q

This inhibits E2F transcription factor

A

Rb

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27
Q

Rb inhibits this transcription factor

A

E2F

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28
Q

Is RAS active or inactive when phosphorylated?

A

Active

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29
Q

To prevent inappropriate growth, these immediately dephosphorylate the RAS-GTP to its inactive form

A

GAP proteins
Are tumor suppressor proteins

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30
Q

GTPase activating protein (tumor suppressor gene) that normally inactivates RAS:GTP –> GDP, and when lost causes neurofibromatosis 1

A

NF1

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31
Q

Tumor suppressor gene that inhibits PI3K/AKt signaling

A

PTEN (phosphatase and tensin homologue)

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32
Q

Autosomal dominant disorder involving loss of function mutation of NF1 (GAP)

A

Neurofibromatosis 1

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33
Q

Neurofibromatosis 1 is caused by this

A

Loss of function mutation of NF1 gene

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34
Q

Autosomal dominant disorder caused by a loss of function mutation in PTEN gene

A

Cowden syndrome

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35
Q

Cowden syndrome is caused by this

A

Loss of function mutation of PTEN gene

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36
Q

Endometrial carcinoma, breast carcinoma, thyroid cancer, hamartomatous intestinal polyps and hamartomatous skin lesions are features of this condition

A

Cowden syndrome

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37
Q

Active form of Rb tumor suppressor gene is this

A

Hypophosphorylated

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38
Q

This binds and inactivates E2F, a pro-growth transcription factor

A

Rb

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39
Q

Rb binds and inactivates this

A

E2F, a pro-growth transcription factor

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40
Q

E2F is this

A

Pro-growth transcription factor

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41
Q

Autosomal dominant condition involving the inheritance of one allele, so only one more cell needs a mutation to produce a tumor

A

Familial Retinoblastoma

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42
Q

Inherited loss of a p53 copy (one hit)
25x risk of malignancy by age 50
Sarcomas, adrenal carcinoma, breast cancer, leukemia

A

Li-Fraumeni Syndrome

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43
Q

Li-Fraumeni Syndrome is an inherited loss of this

A

A p53 copy

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44
Q

Sarcomas and adrenal carcinoma are characteristic of this condition caused by loss of p53 copy

A

Li-Fraumeni Syndrome

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45
Q

Tumor suppressor gene lost in colon cancer

A

APC
Part of WNT signaling pathway to stabilize beta-catenin, a co-transcription factor

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46
Q

Part of WNT signaling pathway to stabilize beta-catenin, a co-transcription factor
Lost in colon cancer

A

APC

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47
Q

APC is a tumor suppressor gene lost in this

A

Colon cancer

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48
Q

Tumor suppressor gene lost in signet ring cancer of breast and stomach

A

CDH1

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49
Q

Tumor suppressor gene that encodes E-cadherin adhesion molecule

A

CDH1

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50
Q

Tumor suppressor gene lost in renal cell carcinomas

A

VHL

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51
Q

Gain of function of these lead to neoplasia

A

Oncogenes

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52
Q

Loss of function mutations of these lead to neoplasia

A

Tumor suppressor genes

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53
Q

Often a single mutation of these is needed for neoplasia (dominant pattern of inheritance)

A

Oncogenes

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54
Q

Usually need loss of both genes of these for neoplasia (recessive pattern of inheritance)

A

Tumor suppressor genes

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55
Q

Growth promoting metabolic alterations
Cells enter preferential fermentative metabolism
Provides excess carbon macromolecules at expense of energy

A

Warburg effect

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56
Q

p53 is this type of apoptotic force

A

Pro-apoptotic

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57
Q

bcl-2 is this type of apoptotic force

A

Anti-apoptotic

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58
Q

This is over-expressed in follicular lymphoma
t(14;18)

A

bcl-2

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59
Q

Over-expression of this results in slow-growing, indolent tumors
Incurable because low proliferation

A

bcl-2

60
Q

Proteins that form channels in mitochondrial membrane

A

Bax/Bak

61
Q

Protein that binds bax/bak and prevents its dimerization
Results in no mitochondrial permeability

A

Bcl-2

62
Q

This protein activates bax/bak and relocates to mitochondrion
Results in increased mitochondrial permeability and caspase activation

A

p53

63
Q

Cellular immortality most often involves this mechanism

A

Telomere

64
Q

Some cancers reactivate telomerase function, and this is one mechanism

A

loss of p53

65
Q

Some cancers have intrinsic telomerase activity by this method

A

Retain stem cell population

66
Q

New vascular supply is needed for tumors to grow beyond this

A

1-2 mm

67
Q

This type of tumor environment promotes HIF-enabled transcription

A

Ischemic

68
Q

This inhibits VEGF
Loss allows VEGF to promote vessel growth (tumor angiogenesis)

A

p53

69
Q

Monoclonal antibody that inhibits VEGF

A

Bevacizumab

70
Q

Bevacizumab inhibits this

A

VEGF
Prevents angiogenesis

71
Q

Transcription factor activated in ischemic tumor environment that promotes transcription of VEGF

A

Hypoxia inducible factor (HIF)

72
Q

Cell adhesion molecule that is often lost or suppressed to allow metastatic epithelial cells to detach from each other

A

E-cadherin

73
Q

In normal cells, epithelial integrins bind this on the matrix

A

Laminin

74
Q

In normal cells, these bind matrix laminin

A

Epithelial integrins

75
Q

In cancer, this is lost, which usually binds matrix laminin
Allows cells to attach to remodeled matrix

A

Integrin

76
Q

In cancer, matrix is induced to produce this
Allows cells to attach to remodeled matrix

A

Fibronectin

77
Q

Morphological stromal reaction to invasion

A

Desmoplasia

78
Q

In order to survive intravascular travel, metastatic cells use this coating for stability and evasion of surveillance

A

Platelet

79
Q

2 complementary adhesion molecules that allow metastatic cancer cell implantation in bone

A

E-cadherin and osteoblast N-cadherin

80
Q

Antigens on tumor cells which are not recognized as self-antigens

A

Neoantigens

81
Q

Tumor cells upregulate this which inhibits APCs

A

CTLA-4

82
Q

Tumor cells upregulate CTLA-4, which inhibits this

A

APCs

83
Q

2 proteins that tumor cells upregulate in order to inhibit/avoid T cell killing

A

CTLA-4 (inhibits APCs)
PD-L1 and PD-L2

84
Q

Anti-CTLA-4 antibody

A

Ipilimumab

85
Q

Ipilimumab is a monoclonal antibody against this

A

CTLA-4

86
Q

Pembrolizumab and Nivolumab are antibodies against this

A

PD-1

87
Q

Atezolizumab, Avelumab and Durvalumab are antibodies against this

A

PD-L1

88
Q

Most frequently mutated gene in human cancer

A

p53

89
Q

Normally p53 is inactivated by this

A

MDM2 ubiquitination

90
Q

Protein that is normally inactivated by MDM2 ubiquitination

A

p53

91
Q

Stressed cells have decrease MDM2 binding, which increases activity of this

A

p53

92
Q

Stressed cells have decreased binding of this, which results in increased p53 activity

A

MDM2

93
Q

This maintains Rb in active hypophosphorylated form

A

p21

94
Q

p21 maintains this in active hypophosphorylated form

A

Rb

95
Q

p53 increases activity of this CDK-inhibitor which maintains Rb in active hypophosphorylated form

A

p21

96
Q

p53 can increase transcription of this to increase mitochondrial permeability and induce apoptosis

A

BAX

97
Q

Tandem nucleotide repeats, normally of uniform constant length
Hallmark of loss of mismatch repair enzymes

A

Microsatellite instability (MSI)

98
Q

Microsatellite instability (MSI) is hallmark of this

A

Loss of mismatch repair enzymes

99
Q

Syndrome of defective MMR enzymes

A

Lynch syndrome

100
Q

System to excise and correct pyrimidine residues cross-linked by UV radiation

A

Nucleotide excision repair

101
Q

Disorder of NER enzyme loss of function (defect in components of excision repair)
HIGH rates of UV induced skin cancers (Squamous cell and Basal cell)

A

Xeroderma Pigmentosa

102
Q

Repair of double stranded DNA breaks and DNA cross-links

A

Homologous recombination

103
Q

Condition caused by Mutations/defects in Homologous recombination factors
Aplastic anemia, leukemia

A

Fanconi anemia

104
Q

Cells that normally break and rejoin DNA, and errors in this produce frequent translocations

A

Lymphoid cells

105
Q

Translocation in Burkitt Lymphoma

A

t(8:14)

106
Q

Translocation of t(8:14) is characteristic of this

A

Burkitt Lymphoma

107
Q

Translocation of t(14:18) is characteristic of this

A

Follicular lymphoma

108
Q

Translocation of t(11:14) is characteristic of this

A

Mantle cell lymphoma

109
Q

Translocation in Follicular Lymphoma

A

t(14:18)

110
Q

Translocation in Mantle Cell Lymphoma

A

t(11:14)

111
Q

Chemical carcinogen that preferentially causes specific mutation in TP53 codon 249

A

Aspergillus aflatoxin

112
Q

Aspergillus aflatoxin results in this condition

A

Hepatocellular carcinoma

113
Q

Hepatocellular Carcinoma can be caused by this chemical carcinogen

A

Aspergillus Aflatoxin

114
Q

Aflatoxin preferentially causes this specific mutation

A

TP53 codon 249 (G:C –> T:A)

115
Q

Type of specific UV radiation that produces pyrimidine dimers, especially T-T pairing

A

UV-B (280-320 nm)

116
Q

Acute myeloid leukemia and Thyroid malignancies can be produced from this

A

Ionizing radiation

117
Q

Infection that infects B cells via CD21 (complement receptor)

A

EBV

118
Q

EBV infects these cells

A

B cells

119
Q

EBV infects B cells via this

A

CD21, complement receptor

120
Q

Infection that binding produces viral encoded proteins, LMP-1 and EBNA-2

A

EBV

121
Q

Viral encoded proteins produced from EBV infecting B cells via CD21

A

LMP-1 and EBNA-2

122
Q

Viral encoded protein with stimulated CD40 activated form that mimics helper T cell signaling, leading to B cell proliferation; also activates bcl2 and prevents apoptosis

A

LMP-1

123
Q

The viral encoded protein LMP-1 results in these 2 main actions

A

B cell proliferation
Prevents apoptosis

124
Q

Viral encoded protein EBNA2 activates this

A

Cyclin D1 (leads to proliferation)

125
Q

Viral encoded protein that activates Cyclin D1, leads to proliferation

A

EBNA2

126
Q

EBV results in polyclonal B cell proliferation, and this condition

A

Infectious Mononucleosis

127
Q

What most commonly causes infectious mononucleosis?

A

EBV infection

128
Q

Infectious mononucleosis involves proliferation of these cells as a result of EBV infection

A

Polyclonal B cell proliferation

129
Q

EBV infection in patient with deficient immune system increases likelihood of this

A

t(8:14) = Burkitt lymphoma

130
Q

This type of infection in patient with deficient immune system increases likelihood of t(8:14), leading to Burkitt Lymphoma

A

EBV

131
Q

Microbial infection that can cause adult T cell leukemia/lymphoma

A

HTLV1

132
Q

Microbial infection that can cause mucosal squamous cell carcinomas

A

HPV 16/18

133
Q

Microbial infection that can cause gastric carcinoma and gastric MALT lymphoma

A

H. pylori

134
Q

Microbial infection that can cause hepatocellular carcinoma

A

Hep C and B

135
Q

Microbial infection that can cause nasopharyngeal carcinoma

A

EBV

136
Q

Microbial infection that can cause B cell lymphomas in immune suppressed patients

A

EBV

137
Q

These tumors often are functional

A

Endocrine

138
Q

Parathyroid adenoma secretes these hormones

A

Prolactin, ACTH

139
Q

Adrenal tumor secretes these hormones

A

Catecholamines (epinephrine)

140
Q

Pancreatic tumor secretes this

A

Insulin

141
Q

Signs and symptoms due to tumor but not explained by mass or function of tissue of origin

A

Paraneoplastic syndromes

142
Q

Hypercatabolic state not explain by low caloric intake
Fat and muscle loss
Most often with advanced cancers
Thought to be due to TNF; other inflammatory mediators

A

Cancer Cachexia

143
Q

A category used to predict behavior based on the tumor morphology
Sometimes uses Degree of Differentiation

A

Tumor grade

144
Q

An assessment of the extent of tumor spread

A

Tumor stage

145
Q

What is tumor grade?

A

Category used to predict behavior based on the tumor morphology

146
Q

What is tumor stage?

A

Assessment of the extent of tumor spread
(describes what the tumor has already done)

147
Q

3 components of tumor stage

A

T = primary tumor spread (tumor size, invasion of specific structures, vascular invasion)
N = are lymph nodes involved
M = metastases beyond lymph nodes

Immunology (21 decks)

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