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Mechanisms of Disease > Neoplasia > Flashcards

Neoplasia Flashcards

1
Q

Describe the Warburg effect?

A

Excessive glycolysis in the presence of oxygen

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2
Q

What are agonists of HER1/2?

A

EGF - epidermal growth factor

TGFα - transforming growth factor

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3
Q

Do carcinomas have mesenchymal or epithelial origin?

A

Epithelial

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4
Q

What are the pathways of spread for metastasis?

A

Direct seeding of body cavities/surfaces

Lymphatic system

Vascular system

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5
Q

Src signaling regulates what?

A

Cytoskeleton

Cell migration

Adhesion

Invasion

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6
Q

What underlying cancers can cause hypoglycemia as a paraneoplastic syndrome. Why?

A

Ovarian carcinoma

Fibrosarcoma

Mesenchymal sarcomas

Produce insulin or insulin-like substance; induces glucose uptake

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7
Q

What is the function of p53?

A

Inhibit cell cycle progression to allow DNA repair

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8
Q

What type of gene promotes proliferation and inhibit cell death?

A

Oncogenes

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9
Q

Describe the TNM system.

A

Numbers are assigned to each characteristic based on a scale for individual cancers

T = tumor size

N = lymph node metastases

M = other metastases

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10
Q

In the epithelium, when dysplasia breaches the basement membrane it is considered ____.

A

Invasive

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11
Q

Metaplasia refers to ____.

A

Replacement of one cell type to another; associated with tissue damage, repair, and regeneration

Ex: Barrett’s Esophagus

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12
Q

What are some of the local effects of a cancerous tumor?

A

Affect function of vital tissue by pressure, obstruction, or infection

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13
Q

Solid tumors cannot be more than ______ in diameter without angiogenesis, as it is the diffusion limit

A

1-2 mm

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14
Q

Where are you most likely to see metastasis via direct seeding?

A

Peritoneal

Any spaces (including joints and subarachnoid)

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15
Q

A sarcoma has _____ stroma and is considered _____.

A

little

“fleshy”

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16
Q

Grading of a tumor is determined by?

A

Cytology

Ex: Pap Smear

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17
Q

The transition between what two phases of the cell cycle is disrupted in most cancers?

A

G1 to S phase

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18
Q

Under hypoxic conditions, Src signaling promotes what?

A

Angiogenesis

(VEGF, MMPs, IL8)

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19
Q

Myc controls _____% of all mammalian genes.

A

10-15%

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20
Q

Does grading or staging have greater clinical value?

A

Staging

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21
Q

What is a teratoma?

A

Tumor derived from totipotent cells; mixture of adult tissue types

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22
Q

What are the ways cancer cells evade the immune system?

A

Antigen loss

HLA mutations (histone compatibility)

Produce immune inhibitors

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23
Q

Stroma refers to what in cancer.

A

Supportive tissue

ex: connective tissue, blood vessels, lymphatics

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24
Q

Mutations in BRCA1/2 are associated with?

A

Inherited breast cancer susceptibility

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25
Q

What is a leiomyoma? Is it highly differentiated or does it lack differentiation?

A

Benign smooth muscle tumor of the uterine wall

Highly differentiated

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26
Q

Does parenchyma or stroma determine tumor behavior?

A

Parenchyma

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27
Q

What cancer is associated with overactivation of HER1/2?

A

Breast cancer

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28
Q

Is a papilloma mesenchymal or epithelial in origin?

A

Epithelial

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29
Q

Is a fibroma mesenchymal or epithelial in origin?

A

Mesenchymal

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30
Q

Is a leiomyoma mesenchymal or epithelial in origin?

A

Mesenchymal

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31
Q

The likelihood of metastasis increases due to what cellular factors?

A

Lack of differentiation

Aggressive local invasion

Rapid growth

Large size

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32
Q

What extracellular stimuli activate Myc?

A

Growth factors

Cytokines

Cell adhesion

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33
Q

What enzymes does Rb interact with?

A

Chromatin remodeling enzymes; has significant impact on global gene expression

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34
Q

Does stroma affect parenchymal behavior or does parenchymal affect stroma behavior?

A

Stroma affects parenchymal behavior

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35
Q

HIF1α induces VEGF, which leads to?

A

Angiogenesis

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36
Q

The following are all characteristics of what class of tumor?

Pleomorphism

Abnormal nuclear morphology

Irregular and increased mitoses

Loss of polarity

Central ischemic necrosis

A

Anaplastic

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37
Q

What glycolytic enzyme is activated by HIF1α?

A

Hexokinase 2 (HK2)

Responsible for initiating glycolysis by phosphorylating glucose into glucose-6-phosphate

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38
Q

Pleomorphism refers to _____?

A

Variations in size and shape of cells

Ex: tumor giant cells in a Rhabdomyosarcoma (malignant tumor of skeletal muscle)

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39
Q

Pathological staging of a tumor is determined by?

A

Biopsies

Clinical staging information

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40
Q

Do carcinomas originate from endoderm, mesoderm, or ectoderm?

A

Any of them

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41
Q

What is the function of cyclins?

A

Activate cyclin-depending kinases (Cdks) at specific points in the cell cycle

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42
Q

What cancer is linked to exposure to Aflatoxin B1?

A

Hepatocellular carcinoma

43
Q

What is the normal function of BRCA1/2?

A

Act as mediators of double-stranded break (DSB) repair

Replication fork collapse recovery

44
Q

Is a cystadenoma mesenchymal or epithelial in origin?

A

Epithelial

45
Q

What is are paraneoplastic syndromes?

A

Cancer patients that have symptoms unrelated to an existing tumor that cannot be explained by new pathology and is not due to systemic effects of hormones or inflammation

46
Q

What is the hallmark characteristic of a papilloma?

A

Fingerlike projections, either micro or macroscopic

47
Q

What are the potential fates of double-stranded DNA repair? (4)

A

Repaired directly

p53-mediated pathways

Apoptosis

Senesce

48
Q

Mesenchymal tumors are derived from?

A

Mesoderm

49
Q

What is the most common pathway for spread of carcinomas?

A

lymphatic system

50
Q

Are veins or arteries more likely to be penetrated by a metastasis?

A

Veins

51
Q

Clinical staging of a tumor is determined by?

A

Physical exam

Imaging

Lab tests

52
Q

How is Rb regulated in the cell?

A

Inhibited by hyperphosphorylation by cyclin/CDK complexes; allows for cell cycle progression

53
Q

How does p53 activate?

A

Complexes with PIDD to form PIDDosome

54
Q

Glycolytic enzymes are expressed at ____ rates in cancer cells.

A

Higher

55
Q

What are the three main stages of carcinogenesis?

A
  1. Initiation/priming
  2. Permanent DNA damage
  3. Additional promoter mutations
56
Q

What is the consequence of acute exposure to Aflatoxin B1 at high levels or exposure in children?

A

Hepatic necrosis

57
Q

Anaplasia refers to ____.

A

Lack of differentiation

58
Q

Is a chondroma mesenchymal or epithelial in origin?

A

Mesenchymal

59
Q

Breast cancer can be induced by what hormone?

A

Estrogen

60
Q

How does merlin act on the cell membrane and the nucleus?

A

Membrane: inhibits RTKs and integrins

Nucleus: inhibits E3 ubiquitin ligase

61
Q

What extracellular stimuli inhibit Myc?

A

Contact-inhibition

TGFβ

Differentiation

62
Q

How does Aflatoxin B1 act on a cell?

A

Causes characteristic mutation on Ser249 of p53

63
Q

Parenchyma refers to ____ in cancer.

A

The cancer cells themselves

64
Q

What must occur in order for Myc to bind to DNA?

A

It must complex with another protein (Max)

65
Q

Anaplasia is a hallmark of ____.

A

Malignancy

66
Q

When a tumor is more differentiated, does that generally indicate a better or worse prognosis?

A

Better prognosis

67
Q

An adenoma is a tumor of?

A

Glands

68
Q

What does cyclin D1 mediate?

A

G1 to S phase transition

69
Q

What kind of gene inhibits proliferation and promotes cell death?

A

Tumor suppressor genes

70
Q

Mutations in cyclin D1 can result in what?

A

Inappropriate entry into S phase

71
Q

What is the function of Rb?

A

Inhibits cell cycle progression and differentiation by interacting with transcription factors

72
Q

BRCA2 acts in?

A

Homologous recombination

73
Q

HIF1α counteracts the activity of what protein? How?

A

Myc

Blocks or displaces it due to overlapping recognition sequences

74
Q

What are the three types of staging of a tumor?

A

Clinical

Pathological

Restaging

75
Q

Staging of a tumor is based on?

A

Location of primary tumor

Tumor size

Lymph node spread (local v. regional)

Distant metastases

76
Q

What is Max?

A

Myc-associated protein X

FOrms a heterodimer with Myc so it can bind to DNA

77
Q

Is a polyp mesenchymal or epithelial in origin?

A

epithelial

78
Q

Staging of a tumor can be determined by?

A

Surgery or imaging

79
Q

What is Aflatoxic B1?

A

Carcinogen produced by Aspergillus (mold that grows on nuts)

80
Q

What is VHL? Function?

A

Von Hippel Lindau protein

Ubiquitin ligase that targets HIF1α for destruction

81
Q

What type of abnormal nuclear morphology would you expect to see in an anaplastic tumor?

A

Unusually large for the cell with variable and irregular shape

Coarse, clumped chromatin that may be hyperchromatic

Abnormally large nucleoli

82
Q

Prostate cancer is dependent on what hormones?

A

Androgens

83
Q

What is Myc?

A

An oncogenic transcription factor that serves as an intracellular sensor and transducer of extracellular stimuli

84
Q

Are adenomas mesenchymal or epithelial in origin?

A

Epithelial

85
Q

Does Ras signaling promote proliferation or inhibit proliferation?

A

Promotes proliferation

86
Q

In the epithelium, when dysplasia is contained by the basement membrane, it is referred to as ______.

A

Carcinoma In situ

87
Q

What is the consequence of chronic low level exposure to Aflatoxin B1?

A

Hepatocellular carcinoma

88
Q

HER1/2 genes code for what protein?

A

Epidermal growth factor receptor (EGFR)

89
Q

What are some of the normal functions of Myc?

A

Cell survival

Cell cycle progression

Cell adhesion

Energy production

Protein biosynthesis

Nucleotide and Amino acid metabolism

90
Q

What causes p53 to activate?

A

Genotoxic stress due to double-stranded DNA breaks

91
Q

Do sarcomas have a mesenchymal or epithelial origin?

A

Mesenchymal

92
Q

What is the protein product of the NF2 gene? What is its function?

A

Merlin

Inhibits proliferation and survival

93
Q

What type of receptor is EGFR?

A

Receptor tyrosine kinase

94
Q

What is a mixed tumor?

A

Divergent differentiation of a neoplastic clone of the SAME germ layer

Ex: mixed tumor of the salivary gland can have epithelial components in the stroma as well as islands of cartilage or bone

95
Q

What is the most common pathway for spread of sarcomas?

A

Vascular system

96
Q

What is HIF1α? Function?

A

Hypoxia-inducible factor

Dimerizes with HIF1β and acts as a transcription factor for survival proteins; especially glycolytic proteins

97
Q

Dysplasia refers to _____.

A

Disordered growth; loss of cellular uniformity and normal organization of tissue

98
Q

What protein is mutated in pheochromocytomas (tumor of the adrenal glands)

A

Max

99
Q

Grading of a tumor assumes that what two aspects of it are related?

A

Behavior and differentiation

100
Q

What is cachexia? Symptoms?

A

Progressive loss of both fat and lean tissue, typically from cancer

Profound weakness, anorexia, anemia

101
Q

Dysplasia is a precursor to ____.

A

Malignancy, but does not always lead to cancer.

102
Q

BRCA1 acts in?

A

Checkpoint activation and DNA repair

103
Q

What enzyme of the citric acid cycle is activated by HIF1α?

A

Pyruvate dehydrogenase kinase

Mechanisms of Disease (13 decks)

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