Cancer... FML Flashcards
1
Q
p 15, p16, p18, p19 inhibit what CDKs
A
CDK4 and CDK6 (only in G1 to S transition)
2
Q
p21, p27, p57
A
Inhibit multiple CDKs
3
Q
Cyclin/CDK regulating G1-S
A
Cylcin D-CDK4, Cyclin D-CDK6, Cyclin E-CDK2
4
Q
Cyclin/CDK regulating S
A
Cyclin A-CDK2 and cyclin A-CDK1
5
Q
Cyclin/CDK regulating G2 to M
A
Cyclin B/CDK1
6
Q
Warburg effect
A
Increased glucose and glutamine uptake, increased glycolysis, decreased OxPhos
7
Q
Wnt/Frizzled pathway
A
Wnt binds to frizzled and disheveled to prevent beta-catenin destruction so nuclear transcription occurs
8
Q
Ovarian carcinoma metastasizes by
A
Seeding of body cavities
9
Q
Carcinomas metastasize by
A
Spreading to regional lymph nodes
10
Q
Sarcomas metastasize by
A
Spreading through blood to lungs and liver
11
Q
Metastatic ovarian carcinomas cause
A
Intestinal obstruction leading to nausea and vomiting
12
Q
Hamartoma
A
Mass of mature but disorganized tissue indigenous to its site
13
Q
Choristoma
A
Mass of normal tissue present outside of normal site
14
Q
Teratoma
A
Benign or malignant neoplasm with components of more than one germ cell layer
15
Q
Polyp
A
Macroscopic projection above mucosal surface
16
Q
Anaplasia
A
Lack of visible differentiation of malignant tumor cells –> larger than undifferentiated cells, bigger nuclei/less cytoplasm, pleomorphic
17
Q
Dysplasia
A
Disordered growth
18
Q
Desmoplasia
A
Formation of abundant fibrous stroma by some carcinomas
19
Q
Carcinoma in situ
A
Tissue with all cytologic features of malignancy without visible invasion
20
Q
Neoplasia
A
cell proliferation that is autonomous, clonal, and irreversible
21
Q
BCR-ABL fusion
A
Chronic myelogenous leukemia (CML)
22
Q
EML4-ALK fusion
A
Lung primary adenocarcinoma
23
Q
Fli-EWS fusion
A
Ewing carcinoma
24
Q
Overexpressed BCL2
A
Follicular lymphoma
25
Overexpressed HGMA2
Parotid pleomorphic adenoma
26
Overexpressed MYC gene
Burkitt lymphoma --\> fastest growing human cancer MYC is the master controller gene --\> codes for telomerase
27
TMRPSS fusion
Prostate adenocarcinoma
28
Imatinib
TKI that inhibits BCR-ABL in CML
29
Crizotinib
Targeted therapy for EML4-ALK for lung primary adenocarcinoma
30
Erlotinib
Blocks mutated EGFR tyrosine kinase (breast carcinoma and lung adenocarcinoma)
31
ERBB1 or EML4-ALK
Tyrosine kinase mutated in lung adenocarcinoma
32
ERBB2 and HER2
Tyrosine kinases mutated in breast carcinoma
33
RAS point mutation
Makes RAS signaling constitutive In 90% of pancreatic adenocarcinomas, 50% of colon, endometrial, and thyroid
34
Vemurafenib
TKI that targets BRAF (downstream of RAS) in hairy cell leukemias and melanomas
35
Two most important tumor suppressor genes
RB and TP53 --\> encode proteins that inhibit G1 to S progression
36
Trastuzumab
Targets HER2 in breast cancer
37
Rb protein
Regulates the G1 to S transition
38
Rb mechanism of regulation
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
39
HPV E7 protein
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
40
Most frequently mutated gene in cancer
TP53
41
Li-Fraumeni syndrome
Inherit one mutated TP53 allele --\> 25x higher risk of developing malignancy by 50
42
MDM2
Protein that stimulates degradation of p53 that is overexpressed in malignancies
43
HPV E6 protein
Binds to and degrades p53 and also stimulates expression of TERT (catalytic subunit of telomerase)
44
Von Hippel Lindau gene product
Causes ubiquitination and degradation of HIF-1
45
VHL germ line mutation
Associated with kidney cancer, pheochromocytoma, and retinal angioma
46
Adenomatous polyposis coli (APC)
Family of proteins tat down regulate growth-promoting signaling pathways --\> germ line mutation associated with familial adenomatous polyposis --\> thousand of colon polyps
47
APC function
APC degrades beta-catenin to prevent transcription of MYC and cyclin D genes. WNT signaling prevents APC from degrading beta-catenin
48
E-cadherin (CDH1 gene)
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
PTEN gene
tumor suppressor that serves as a brake for PI3K/AKT arm of RTK pathway --\> mutations notorious in endometrial carcinoma
50
NF1 gene
Encodes Neurofibromin 1 --\> negative regulator of RAS
51
NF2 gene
Encodes Neurofibromin 2 --\> cytoskeletal protein involved in contact inhibition
52
WT1 gene
Encodes TF that is required for normal development of genitourinary tissue --\> germ line mutation causes Wilms tumor (pediatric kidney cancer)
53
PTCH1 gene
Encodes membrane receptor that is negative regulator of hedgehog pathway --\> germ line mutation causes Gorlin syndrome, associated with basal cell carcinoma and medulloblastoma
54
Glioblastoma microscopic findings
Lymphocytes palisaded around necrotic area (bottom left)
55
Tumoral CDKN2A mutation
Found in 70% of glioblastoma
56
NMYC gene amplification
Feature of neuroblastoma --\> neural crest-derived cells that occurs outside of brain in small children
57
Thrombospondin-1
Angiogenesis inhibitor under transcriptional control by p53
58
Proteins unregulated by cancers to degrade basement membrane
MMP, cathepsin D, urokinase plasminogen activator
59
CD44 (HCAM)
Protein expressed by some tumor cells that may allow them to enter lymphoid tissues
60
Breast cancer bone metastasis
Cancer cells secrete PTHRP which stimulates osteoblasts to produce RANKL --\> stimulates osteoclasts to breakdown bone and release IGF and TGF-B
61
SNAIL and TWIST
downregulate expression of E-cadherin
62
Hereditary nonpolyposis colon cancer
Defective DNA repair enzymes --\> microsatelite instability causes mutations that are not repaired
63
Uterine cervical squamous carcinoma
Apical cells typically appear more flattened with clear cytoplasm --\> in carcinoma, all cells look like the basal cells
64
Inflammatory bowel disease can cause
carcinoma of the colon
65
Chronic hepatitis (especially from HepC) can cause
Hepatocellular carcinoma
66
Chronic pancreatitis can cause
Pancreatic carcinoma
67
Chronic cholecystitis can cause
Gallbladder carcinoma
68
Chronic epithelial injury typically leas to
Metaplasia
69
H pylori and cancer
Chronic active gastritis caused by H pylori leads to gastric carcinoma --\> CagA cytotoxin
70
CagA protein form H pylori
1. Depolarizes cell membrane 2. Activates cell proliferation pathways 3. Causes degradation of p53
71
Intestinal metaplasia
Goblet cells found in gastric mucosa --\> metaplasia
72
Leukoplakia
thickening of squamousepithelium that may occur in the oral cavity or on the penis or vulva --\> hyperkeratosis
73
Immunodeficient patients are more susceptible to
1. B cell lymphoma caused by EBV
2. Kaposi sarcoma caused by Herpes 8
3. Squamous cell carcinoma caused by HPV
74
Cafe au lait spots
Associated with neurofibromatosis type 1 --\> seizures and skeletal abnormalities also common --\> overactive Ras due to mutated neurofibromin1
75
High grade squamous intraepithelial lesion in PAP smear
Cells look basaloid
76
Triple negative breast cancer microscopic appearance
Basaloid
77
Melanomas are typically caused by
Sun bathing Carcinomas are from cumulative typical exposure
78
UVB mechanism fo carcinogenicity
Pyrimidine dimer formation --\> must be excised and repaired but can overwhelm repair machinery
79
Melanoma microscopic appearance
large, round cells with lightly basophilic cytoplasm and melanin
80
Hepatocellular carcinoma
Usually in people over 60
Predominantly males
Caused by HepC virus
Manifests as cirrhosis
81
HepC mechanism of cirrhosis
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
PSA tests for
prostate adenocarcinoma
83
CEA tests for
colon, stomach, pancreas, and breast cancers
84
AFP tests for
Hepatocellular carcinomas, teratocarcinomas, and embryonal cell carcinomas
85
HCG tests for
Testicular tumors
86
CA-125 tests for
Ovarian cancer
87
Immunoglobulins test for
Multiple myeloma and other plasma cell tumors
88
APC, TP53, and RAS sequences in stool
Colorectal carcinoma
89
TP53 mutations and hypermethylated genes in sputum
Lung cancer --\> if in saliva it is head and neck cancer
90
TP53 mutations in urine
bladder cancer
91
TGF-B secreted by cancer cells
Immunosuppresant to prevent immune system activation
92
Difference between melanoma and benign nevus
Nevus cells are smaller and lack the pleomorphism of melanoma
93
Aflatoxin B
Toxin produce by some strains of Aspergillus contaminating food that is correlated hepatocellular carcinoma
94
Colon cancer molecular progression
1. Inactivation of APC gene 2. Activation of RAS gene 3. Loss of SMAD (18q tumor suppressor) 4. Loss of TP53
95
Most common symptoms of lung cancer
1. Cough (70%) 2. Hemoptysis (50%) 3. Dyspnea (25%)
96
Colon cancer symptoms
1. Abdominal pain (44%) 2. Change in bowel habits (43%) 3. Hematochezia or melena (40%)
97
Small cell carcinoma microscopic appearance
Small cells with inconspicuous cytoplasm and irregular nuclei
98
3 most common paraneoplastic syndromes
1. Hyperclacemia 2. Cushing syndrome (ACTH) 3. Carcinoid syndrome (seretonin)
99
Symptoms of hypercalcemia
Nausea, vomiting, constipation, polyuria, disorientation, lethargy, seizures --\> caused by PTHRP which induces osteoclast activity
100
Cushing syndrome signs and symptoms
Weight gain, central obesity, moon face, weakness, glucose intolerance, depression, psychosis, buffalo hump dorsal neck fat deposition
101
Most common cause of Cushing syndrome
Pituitary adenoma producing excess ACTH Small cell carcinoma of the lung is common too
102
Carcinoid syndrome
Attacks of cutaneous flushing, diarrhea, cramps, nausea, vomiting, cough
103
Bright red blood in stool
Colon tumor on left side --\> "Red is not right"
104
Black stool
Colon tumor on right side
105
c-kit (oncogene) mutation leads to
Gastrointestinal stromal tumor
106
Wha do you treat c-kit mutations with
imatinib --\> Controls GIST tumor
107
Treatment for adenocarcinoma of the lung with EGFR activating mutation
Erlotinib is first line of treatment
108
Crizotinib
Used to treat lung cancer with EML4-ALK mutation
109
Bevacizumab treats
glioblastoma
110
Sunitinib
Treats renal cell carcinoma --\> prevents signaling of VEGF
111
Tamoxifen treats
Estrogen receptor positive breast cancers
112
Everolimus used for
Breast cancer once tamoxifen treatment has failed
113
Enzalutamide treats
metastatic prostate cancer --\> androgen receptor blocker
114
Vemurafenib used for
Treatment of melanoma with BRAF V600 mutation
115
Vismodegib treats
Basal cell carcinoma --\> blocks Hedgehog signaling
