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CMOD Path > Cancer... FML > Flashcards

Cancer... FML Flashcards

1
Q

p 15, p16, p18, p19 inhibit what CDKs

A

CDK4 and CDK6 (only in G1 to S transition)

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2
Q

p21, p27, p57

A

Inhibit multiple CDKs

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3
Q

Cyclin/CDK regulating G1-S

A

Cylcin D-CDK4, Cyclin D-CDK6, Cyclin E-CDK2

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4
Q

Cyclin/CDK regulating S

A

Cyclin A-CDK2 and cyclin A-CDK1

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5
Q

Cyclin/CDK regulating G2 to M

A

Cyclin B/CDK1

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6
Q

Warburg effect

A

Increased glucose and glutamine uptake, increased glycolysis, decreased OxPhos

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7
Q

Wnt/Frizzled pathway

A

Wnt binds to frizzled and disheveled to prevent beta-catenin destruction so nuclear transcription occurs

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8
Q

Ovarian carcinoma metastasizes by

A

Seeding of body cavities

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9
Q

Carcinomas metastasize by

A

Spreading to regional lymph nodes

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10
Q

Sarcomas metastasize by

A

Spreading through blood to lungs and liver

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11
Q

Metastatic ovarian carcinomas cause

A

Intestinal obstruction leading to nausea and vomiting

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12
Q

Hamartoma

A

Mass of mature but disorganized tissue indigenous to its site

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13
Q

Choristoma

A

Mass of normal tissue present outside of normal site

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14
Q

Teratoma

A

Benign or malignant neoplasm with components of more than one germ cell layer

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15
Q

Polyp

A

Macroscopic projection above mucosal surface

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16
Q

Anaplasia

A

Lack of visible differentiation of malignant tumor cells –> larger than undifferentiated cells, bigger nuclei/less cytoplasm, pleomorphic

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17
Q

Dysplasia

A

Disordered growth

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18
Q

Desmoplasia

A

Formation of abundant fibrous stroma by some carcinomas

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19
Q

Carcinoma in situ

A

Tissue with all cytologic features of malignancy without visible invasion

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20
Q

Neoplasia

A

cell proliferation that is autonomous, clonal, and irreversible

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21
Q

BCR-ABL fusion

A

Chronic myelogenous leukemia (CML)

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22
Q

EML4-ALK fusion

A

Lung primary adenocarcinoma

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23
Q

Fli-EWS fusion

A

Ewing carcinoma

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24
Q

Overexpressed BCL2

A

Follicular lymphoma

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25
Q

Overexpressed HGMA2

A

Parotid pleomorphic adenoma

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26
Q

Overexpressed MYC gene

A

Burkitt lymphoma –> fastest growing human cancer MYC is the master controller gene –> codes for telomerase

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27
Q

TMRPSS fusion

A

Prostate adenocarcinoma

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28
Q

Imatinib

A

TKI that inhibits BCR-ABL in CML

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29
Q

Crizotinib

A

Targeted therapy for EML4-ALK for lung primary adenocarcinoma

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30
Q

Erlotinib

A

Blocks mutated EGFR tyrosine kinase (breast carcinoma and lung adenocarcinoma)

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31
Q

ERBB1 or EML4-ALK

A

Tyrosine kinase mutated in lung adenocarcinoma

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32
Q

ERBB2 and HER2

A

Tyrosine kinases mutated in breast carcinoma

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33
Q

RAS point mutation

A

Makes RAS signaling constitutive In 90% of pancreatic adenocarcinomas, 50% of colon, endometrial, and thyroid

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34
Q

Vemurafenib

A

TKI that targets BRAF (downstream of RAS) in hairy cell leukemias and melanomas

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35
Q

Two most important tumor suppressor genes

A

RB and TP53 –> encode proteins that inhibit G1 to S progression

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36
Q

Trastuzumab

A

Targets HER2 in breast cancer

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37
Q

Rb protein

A

Regulates the G1 to S transition

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38
Q

Rb mechanism of regulation

A

Hypophosphorylated Rb binds to E2F to prevent transcription of S phase genes. Growth factors stimulate Cyclin/CDK complexes which phosphorylates Rb to release E2F and transcription of S phase genes occurs

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39
Q

HPV E7 protein

A

Protein that binds to E2F binding pocket of Rb to prevent sequestration of E2F –> also inactivated p21 and p27 and activates cyclins E and A

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40
Q

Most frequently mutated gene in cancer

A

TP53

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41
Q

Li-Fraumeni syndrome

A

Inherit one mutated TP53 allele –> 25x higher risk of developing malignancy by 50

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42
Q

MDM2

A

Protein that stimulates degradation of p53 that is overexpressed in malignancies

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43
Q

HPV E6 protein

A

Binds to and degrades p53 and also stimulates expression of TERT (catalytic subunit of telomerase)

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44
Q

Von Hippel Lindau gene product

A

Causes ubiquitination and degradation of HIF-1

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45
Q

VHL germ line mutation

A

Associated with kidney cancer, pheochromocytoma, and retinal angioma

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46
Q

Adenomatous polyposis coli (APC)

A

Family of proteins tat down regulate growth-promoting signaling pathways –> germ line mutation associated with familial adenomatous polyposis –> thousand of colon polyps

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47
Q

APC function

A

APC degrades beta-catenin to prevent transcription of MYC and cyclin D genes. WNT signaling prevents APC from degrading beta-catenin

48
Q

E-cadherin (CDH1 gene)

A

Beta-catenin binds to cytoplasmic tail of E-cadherin. When a wound disrupts cell contacts, beta-catenin is released to allow for gene transcription

49
Q

PTEN gene

A

tumor suppressor that serves as a brake for PI3K/AKT arm of RTK pathway –> mutations notorious in endometrial carcinoma

50
Q

NF1 gene

A

Encodes Neurofibromin 1 –> negative regulator of RAS

51
Q

NF2 gene

A

Encodes Neurofibromin 2 –> cytoskeletal protein involved in contact inhibition

52
Q

WT1 gene

A

Encodes TF that is required for normal development of genitourinary tissue –> germ line mutation causes Wilms tumor (pediatric kidney cancer)

53
Q

PTCH1 gene

A

Encodes membrane receptor that is negative regulator of hedgehog pathway –> germ line mutation causes Gorlin syndrome, associated with basal cell carcinoma and medulloblastoma

54
Q

Glioblastoma microscopic findings

A

Lymphocytes palisaded around necrotic area (bottom left)

55
Q

Tumoral CDKN2A mutation

A

Found in 70% of glioblastoma

56
Q

NMYC gene amplification

A

Feature of neuroblastoma –> neural crest-derived cells that occurs outside of brain in small children

57
Q

Thrombospondin-1

A

Angiogenesis inhibitor under transcriptional control by p53

58
Q

Proteins unregulated by cancers to degrade basement membrane

A

MMP, cathepsin D, urokinase plasminogen activator

59
Q

CD44 (HCAM)

A

Protein expressed by some tumor cells that may allow them to enter lymphoid tissues

60
Q

Breast cancer bone metastasis

A

Cancer cells secrete PTHRP which stimulates osteoblasts to produce RANKL –> stimulates osteoclasts to breakdown bone and release IGF and TGF-B

61
Q

SNAIL and TWIST

A

downregulate expression of E-cadherin

62
Q

Hereditary nonpolyposis colon cancer

A

Defective DNA repair enzymes –> microsatelite instability causes mutations that are not repaired

63
Q

Uterine cervical squamous carcinoma

A

Apical cells typically appear more flattened with clear cytoplasm –> in carcinoma, all cells look like the basal cells

64
Q

Inflammatory bowel disease can cause

A

carcinoma of the colon

65
Q

Chronic hepatitis (especially from HepC) can cause

A

Hepatocellular carcinoma

66
Q

Chronic pancreatitis can cause

A

Pancreatic carcinoma

67
Q

Chronic cholecystitis can cause

A

Gallbladder carcinoma

68
Q

Chronic epithelial injury typically leas to

A

Metaplasia

69
Q

H pylori and cancer

A

Chronic active gastritis caused by H pylori leads to gastric carcinoma –> CagA cytotoxin

70
Q

CagA protein form H pylori

A
  1. Depolarizes cell membrane 2. Activates cell proliferation pathways 3. Causes degradation of p53
71
Q

Intestinal metaplasia

A

Goblet cells found in gastric mucosa –> metaplasia

72
Q

Leukoplakia

A

thickening of squamousepithelium that may occur in the oral cavity or on the penis or vulva –> hyperkeratosis

73
Q

Immunodeficient patients are more susceptible to

A
  1. B cell lymphoma caused by EBV
  2. Kaposi sarcoma caused by Herpes 8
  3. Squamous cell carcinoma caused by HPV
74
Q

Cafe au lait spots

A

Associated with neurofibromatosis type 1 –> seizures and skeletal abnormalities also common –> overactive Ras due to mutated neurofibromin1

75
Q

High grade squamous intraepithelial lesion in PAP smear

A

Cells look basaloid

76
Q

Triple negative breast cancer microscopic appearance

77
Q

Melanomas are typically caused by

A

Sun bathing Carcinomas are from cumulative typical exposure

78
Q

UVB mechanism fo carcinogenicity

A

Pyrimidine dimer formation –> must be excised and repaired but can overwhelm repair machinery

79
Q

Melanoma microscopic appearance

A

large, round cells with lightly basophilic cytoplasm and melanin

80
Q

Hepatocellular carcinoma

A

Usually in people over 60

Predominantly males

Caused by HepC virus

Manifests as cirrhosis

81
Q

HepC mechanism of cirrhosis

A

Viral infection induces regeneration NFKB pathway activated preventing apoptosis Mutations accumulate leading to hepatocellular carcinoma –> HCV core protein may have direct effect on tumorigenesis

82
Q

PSA tests for

A

prostate adenocarcinoma

83
Q

CEA tests for

A

colon, stomach, pancreas, and breast cancers

84
Q

AFP tests for

A

Hepatocellular carcinomas, teratocarcinomas, and embryonal cell carcinomas

85
Q

HCG tests for

A

Testicular tumors

86
Q

CA-125 tests for

A

Ovarian cancer

87
Q

Immunoglobulins test for

A

Multiple myeloma and other plasma cell tumors

88
Q

APC, TP53, and RAS sequences in stool

A

Colorectal carcinoma

89
Q

TP53 mutations and hypermethylated genes in sputum

A

Lung cancer –> if in saliva it is head and neck cancer

90
Q

TP53 mutations in urine

A

bladder cancer

91
Q

TGF-B secreted by cancer cells

A

Immunosuppresant to prevent immune system activation

92
Q

Difference between melanoma and benign nevus

A

Nevus cells are smaller and lack the pleomorphism of melanoma

93
Q

Aflatoxin B

A

Toxin produce by some strains of Aspergillus contaminating food that is correlated hepatocellular carcinoma

94
Q

Colon cancer molecular progression

A
  1. Inactivation of APC gene 2. Activation of RAS gene 3. Loss of SMAD (18q tumor suppressor) 4. Loss of TP53
95
Q

Most common symptoms of lung cancer

A
  1. Cough (70%) 2. Hemoptysis (50%) 3. Dyspnea (25%)
96
Q

Colon cancer symptoms

A
  1. Abdominal pain (44%) 2. Change in bowel habits (43%) 3. Hematochezia or melena (40%)
97
Q

Small cell carcinoma microscopic appearance

A

Small cells with inconspicuous cytoplasm and irregular nuclei

98
Q

3 most common paraneoplastic syndromes

A
  1. Hyperclacemia 2. Cushing syndrome (ACTH) 3. Carcinoid syndrome (seretonin)
99
Q

Symptoms of hypercalcemia

A

Nausea, vomiting, constipation, polyuria, disorientation, lethargy, seizures –> caused by PTHRP which induces osteoclast activity

100
Q

Cushing syndrome signs and symptoms

A

Weight gain, central obesity, moon face, weakness, glucose intolerance, depression, psychosis, buffalo hump dorsal neck fat deposition

101
Q

Most common cause of Cushing syndrome

A

Pituitary adenoma producing excess ACTH Small cell carcinoma of the lung is common too

102
Q

Carcinoid syndrome

A

Attacks of cutaneous flushing, diarrhea, cramps, nausea, vomiting, cough

103
Q

Bright red blood in stool

A

Colon tumor on left side –> “Red is not right”

104
Q

Black stool

A

Colon tumor on right side

105
Q

c-kit (oncogene) mutation leads to

A

Gastrointestinal stromal tumor

106
Q

Wha do you treat c-kit mutations with

A

imatinib –> Controls GIST tumor

107
Q

Treatment for adenocarcinoma of the lung with EGFR activating mutation

A

Erlotinib is first line of treatment

108
Q

Crizotinib

A

Used to treat lung cancer with EML4-ALK mutation

109
Q

Bevacizumab treats

A

glioblastoma

110
Q

Sunitinib

A

Treats renal cell carcinoma –> prevents signaling of VEGF

111
Q

Tamoxifen treats

A

Estrogen receptor positive breast cancers

112
Q

Everolimus used for

A

Breast cancer once tamoxifen treatment has failed

113
Q

Enzalutamide treats

A

metastatic prostate cancer –> androgen receptor blocker

114
Q

Vemurafenib used for

A

Treatment of melanoma with BRAF V600 mutation

115
Q

Vismodegib treats

A

Basal cell carcinoma –> blocks Hedgehog signaling

CMOD Path (7 decks)

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