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Neoplasia II Flashcards

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1
Q

Who is the guardian of the genome?

A

p53

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2
Q

What hereditary germline mutations lead to breast cancer at an early age?

A

BRCA-1 and 2

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3
Q

What are Gatekeepers?

A

genes that directly control tumor growth, i.e. tumor suppressors and oncogenes

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4
Q

What are Caretakers?

A

genes that affect genetic stability by causing defective DNA repair

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5
Q

What are some defects in gene repair?

A 
BRCA 1, 2
HNPC
Xeroderma pigmentosa
Ataxia telangiectasia
Bloom syndrom
Fanconi anemia
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6
Q

Follicular B cell lymphomas have a blank translocation that fuses with what?

A

Have a t translocation that fuses with BCL2 gene (chr. 18)

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7
Q

What is the primary mechanism of follicular B cell lymphomas?

A

Evasion of apoptosis. Fusion of BCL2 gene with active IgH locus on chromosome 14 results in over production of BCL2 (anti-apoptotic)

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8
Q

Sustained angiogenesis is required for a tumor to grow over?

A

2 mm

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9
Q

What is angiogenesis normally inhibited by?

A

Thrombomodulin (p53 induced) and destruction of HIF-1alpha (VHL)

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10
Q

What happens with HIF and VHL during tumor hypoxia?

A

Tumor hypoxia turns of VHL, so that HIF-1alpha produces VEGF

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11
Q

What are the four steps of cancer invasion?

A
  1. Detachment of tumor cells from each other
  2. Degradation of basement membrane and ECM
  3. Attachment of tumor cells to basement membrane
  4. Migration
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12
Q

What is bevacizumab?

A

Anti VEGF agent. Only mildly helpful

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13
Q

What is the angiogenic switch mediated by?

A

HIF1alpha, FGF, loss of p53, decreases thromodulin 1

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14
Q

Tumors need to overcomes what anti-angiogenic factors for sustained angiogenesis?

A

Angiostatin, Endostatin, and Vasculostatin

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15
Q

For cancer invasion, detachment of cells is mediated by what?

A

Down-regulation of E cadherin or mutated catenin

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16
Q

For cancer invasion, attachment of cells to exposed basement membrane is mediated by what?

A

Fibronectin and laminin receptors

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17
Q

Where does colon cancer generally metastasize to?

A

Liver

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18
Q

Where do prostate and breast cancer generally metastasize to?

A

Bone

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19
Q

What is the mechanism for metastatic organ tropism?

A

Differential concentration of endothelial cell ligands for adhesion molecules in different organs
Chemokines (ie CXCR4 and CCr7 receptors in breast cancer)

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20
Q

What is tumor embolus?

A

Tumor cells that invade veins go to the lungs and elicit formation of blood clot around them

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21
Q

What is responsible for the organization of a tumor embolus?

A

Organized by fibroblasts

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22
Q

What are chemical carcinogens?

A

Initiators cause mutations, which can potentially become irreversible

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23
Q

Do promoters cause reversible or irreversible proliferation of initiated cells?

A

Reversible

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24
Q

What are direct chemical carcinogens?

Study These Flashcards
A

Electrophiles

25
What are indirect chemical carcinogens?
Require metabolic activation of procarcingens commonly by CYP450 mono-oxygenases
26
What are some examples of indirect chemical carcinogens?
Estrogen, alcohol, anti-cancer drugs, asbestos, polycyclic and heterocyclic aromatic hydrocarbons, aromatic amines, amides, and azo dyes, etc
27
What carcinogens have long latent period (yrs-decade)
Radiation
28
UV light causes what?
Skin cancer
29
Radiation therapy can cause what type of cancer?
Sarcomas
30
Nuclear power plant leaks cause what type of cancer?
Thyroid Cancer
31
What are some microbial carcinogens?
HCV, HBV, HPV, and helicobacter pylori
32
What microbial carcinogens cause hepatic cancer?
HCV and HBV
33
What microbial carcinogens cause lymphoma?
HBV
34
What microbial carcinogens cause uterine cervical cancer?
HPV
35
What microbial carcinogens cause gastric carcinoma and lymphoma?
Helicobacter pylori
36
What are some tumor antigens?
Mutated oncogene products Products of other mutated genes Overly or aberrantly expressed proteins Oncogenic viral products
37
What are even more tumor antigens?
``` Oncofetal antigens (CEA, AFP) Altered cell surface glycolipids (CA-125, CA-19-9) Cell type specific differentiation antigens ```
38
What is the principal immune surveillance mechanisms?
CD8
39
What are other immune surveillance mechanisms?
NK cells (activated by IL2), macrophages, and antibodies
40
What are some resistance mechanisms to immune surveillance?
``` Selective outgrowth of Ag-neg cells Decreased MHC molecules Lack of co stimulation Ag masking Apoptosis of CD8's Immunodeficiency ```
41
What are paraneoplastic syndromes?
Symptoms not attributable to direct effects of tumor ( or hormones native to primary tumor organ)
42
What percentage of patients do paraneoplastic syndromes occur in?
10%, not counting cachexia
43
What can be the earliest manifestation of occult tumor?
paraneoplastic syndrome
44
Can paraneoplastic syndrome be sickening or fatal by themselves?
Yes
45
Can paraneoplastic syndrome mimic metastatic disease?
Yes
46
What are examples of paraneoplastic syndromes?
``` Hypercalcemia (most common) Cushing syndrome Syndrome of inappropriate ADH Hypoglycemia Carcinoid syndrome (serotonin) eaton-lamberts syndrome (myasthenia) ```
47
What are symptoms of hypercalcemia of malignancy?
nausea, vomiting, constipation, polyuria, disorientation, lethargy, seizures
48
What are mechanisms of hypercalcemia?
Parathyroid hormone related protein
49
How do you treat hypercalcemia?
Hydration and biphosphonates
50
What lung cancer types most commonly causes hypercalemia?
Squamous cell carcinoma
51
What are signs and symptoms of Cushing syndrome?
Weight gain, central obesity, moon face, weakness, hirutism, HTN, glucose intolerance, depression, psychosis, broad red abdominal striae, buffalo hump deposition, plethora, osteoporosis, menstrual irregularity, muscle wasting
52
What is the most common source of cushing syndrome?
Pituitary carcinoma: ACTH | Small cell carcinoma of lung as well
53
What are symptoms of Carcinoid syndrome?
cutaneous flushing, diarrhea, cramps, nausea, vomiting, cough
54
What are more random examples of paraneoplastic syndromes that no one gives a fuck about?
Acanthosis Dermatomyositis Hypertrophic osteoarthropathy Migratory thromboplebitis (Trousseau syndrome) Marantic (non bacterial thrombotic) endocarditis
55
What determines tumor stage?
Anatomic extent, including primary tumor size, extent of lymph node, and distant metastases
56
What is tumor grade?
Qualitative assessment of the differentiation of a tumor. In other words, the extent to which it resembles normal tissue at primary site?
57
What are the two stages of cancer diagnosis?
1. Discovery | 2. Specific diagnosis
58
What is the discovery phase of diagnosing cancer?
Symptoms, signs, radiology, and serum markers
59
What is the specific diagnostic phase of diagnosing cancer?
Biopsy: fine needle aspiration cytology, exfoliative cytology

Pathology (6 decks)

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