Oncology DIT Flashcards
Most prevelent Cancers in Males and Females
Males
- Prostate
- Lung
- Colon
Women
- Breast
- Lung
- Colon
- uterus
Cancer w/ highest mortality in M and F
Males
- Lung
- Prostate
- Colon
- Pancreatic
Females
- Lung
- Breast
- Colon
- Pancreatic
What is an oncogene?
-Quinessential example?
Proto -Oncogenes normally regulate signal for cell growth, lack of response due to a mutation -> oncogene. Only one mutation is needed -> gain of function
RAS (G protein in the MAP kinase pathway that is always on -> cancer)
What is a tumor suppressor gene?
Quientessential example?
Tumor suppressor genes regulate the cell cycle. They but on the brakes while DNA repair goes on and encourages apoptosis if not
BOTH alleles must be lost for be cancerous
p53(TF for p21 and blocking G1-S phase)
RB (hypophos binds to ETF)
are classic
Retinoblastoma herititable vs sporadic
Screen kids how?
1/4 is bilateral w/ Rb tumor suppressor mutation inherited (have one KO, a lot easier to have the other go)
3/4 are sporadic meaning both alleles were lost sporadically
(overall 60% mutations sporadic, 40% inheritied)
See a white reflex in the kids eye instead of red
rb is ?
Mutated in what CA (2)
tumor suppressor gene that inhibits E2F when hypophosphorylated
blocks G1-S phase
Retinoblastoma and osteosarcoma
p53 is?
tumor suppressor gene lost in most cancers
Acts through p21 to cause cell arrest
causes apoptosis through transcription of BAX if DNA repair not complete
BRCA1 and 2 is?
Mutated in what CA(2)
tumor suppressor gene involved in DNA repair
Ovarian and Breast
APC is?
Mutated in what CA
is a tumor suppresor gene
mutated in colorectal CA in familal adenomatous polyposis
WT1 is?
mutated in what CA
tumor suppresor gene
mutated in Wilms tumor
NF1 is?
mutated in what CA
tumor suppresor gene involved q/ RAS GTPase activating protein - > cutaneous neurofibromas
Chromosome 17
mutated in nerofibromatosis type 1
NF2 is ?
mutated in what CA?
tumor suppresor gene on chromosome 22
mutated in neurofibromatosis type 2 -> bilateral acoustic schwannomas
DPC 4 is?
mutated in what CA
tumor suppresor gene
Deleated in Pancreatic Cancer
DCC is?
mutated in what CA
tumor suppresor gene
Deleted in Colon Cancer
VHL is?
mutated in what CA?
tumor suppresor gene implicated in von hippel lindau
TSC is?
mutated in what CA?
tumor suppresor gene implicated in tuberous sclerosis
abl is?
mutated in what CA
oncogene -> mutated Tyrosine kinase that is always on w? proximity for BCR (9:22)
CML
c-myc is?
Mutated in what CA
oncogene leading to a transcription factor
mutated in Burketts
bcl 2 is?
mutated in what CA?
oncogene-> anti apoptotic molecule
mutated in follicular and undifferentiated lymphomas
HER2/neu is?
mutated in what CA?
oncogene-> tyrosine kinase
breast
ovarian
gastric CA
ras is?
mutated in what CA? (4 types)
oncogene -> mutated G protein -> constitutively active MAP kinase -> cell proliferation
quitessential oncogene
K -Ras - colon, lung, pancreatits
H-Ras - bladder, kidney (hematuria)
N-Ras- melanomas ans hematologic
also follicular thyroid carcinoma
L myc is?
Mutated in what CA
oncogene-> mutated TF
lung tumor (small cell)
N-myc is?
Mutated in what CA?
oncgone -> mutated TF
neuroblastoma
Ret is?
mutated in what CA(3)
oncogene-> mutated tyrsine kinase
MEN2A
MEN2B
Papillary carcinoma of the thyroid
afalatoxin CA risk
Hepatocellular
vinyl choride CA risk
angiosarcoma - liver
odd smoking CA risks (3)
pancreatic
transitional cell bladder
renal cell carcinoma
inherited predespositions to CA are inherited in what form?
Examples
inherited in auto dominant pattern
APC, BRCA, RET
aspestos exposure CA (2)
bronchogenic carinoma **
mesothelioma
Arsenic exposure CA(2)
squamous cell carcinoma of skin
angiosarcoma
napthalene CA risk?
transiotional cell
benzyne CA risk
leukemia/lymphoma
beryllym CA risk
lung CA
Radiation CA risk(3)
ALL
AML
thyroid CA
UV radiation of harm?
What CA risk (3)
UVB -> pyrimadine dimers
UVA, free radicals
EBV associated w/ (3) CA
Hodgins lymphoma
burkitts lymphoma
nasopharyngeal carcinoma
liver fluke (clonorchis sinensis) associated w/ what CA
cholangiocarcinoma
HCV risk of what CA (2)
Hepatocellular CA
papillary thyrois CA
Down syndrome associated CA (2)
ALL**
AML
Tuberous sclerosis CA (3)
giant cell astrocytoma
cardiac rhabdomyoma
renal angiomyyolipoma
pagers disease of the bone CA risk? (2)
secondary osteosarcoma
fibrosarcoma
Hashimotos disease associated w/ what CA
B cell marginal lymphoma
Dyplastic nevi CA
melanoma
vulvar leukoplakia CA risk
squamous cell
ataxia telangirtasia CA risk
decreased DNA repair
-> leukemia and lymphoma
Hyperplasia means?
increased number of cells
- reversible
metaplasia means?
change in cell type from one to another
-reversible
dysplasia means?
abnormal cell growth w/ loss of cell orientation, shape and size(disorganized)
reversible
anaplasia means?
characterized by (4)
abnormal cells lacking differentiation, cells regress and become less differentiated ->
- high nuclear :cytoplasmic ratio
- prominent nucleoli
- clumping of nuclear chromatin
- many mitotic spindles
Neoplasm means?
clonal proliferation of cells that is uncontrolled and excessive
neoplasia may be benign or malignant
Grade of a tumor looks at?
the amount of differentiation, high grade = less differentiation
Stage of a tumor refers to?
the amount of localization or spread from the primary site
TNM
Tumor Size
Nodes
METS
Benign epithelial tumor is (2)
adenoma - glandular look even if not derived
Papilloma - finger like projection
Malignant epithelial tumor is (2)
Spreads how?
adenocarcioma
papillary carcinoma
spreads via lymphatics
Malignant mesenchymal tumors generally end w?
Spreads?
sarcoma
spreads hematogenously, usually
benign mesenchymal CA rarely -> malignant (as epithelial CA does)
Benign vs malignant CA of blood vessel
Hemangioma
Angiosarcoma
Benign vs malignant CA of the smooth muscle
leiomyoma
leiomyosarcoma
benign vs malignant CA of striated muscle
rhabdomyoma
rhabdomyosarcoma
benign vs malignant CA of bone
osteoma
osteosarcoma
benign vs malignant CA of Fat
lipoma
liposarcoma
Harmatoma
growth of mature tissue that is endogenous to the site where it arises,
a lot of normal tissue
Tumor marker in colorectal CA
CEA
-also detected in pancreatic CA as well (w/ CA 19-9)
CEA marker(2)
tumor marker for Colorectal and Pancreatic
Tumor marker for HCC?
Alpha fetoprotein
- aslo in nonseminomatous germ cell tumors
AFP tumor marker(2)
hepatocellular colorectal cancer
nonseminomatous germ cell tumors
beta hCG tumor marker (2)
hydatriform moles
Choriocarcinoma
Tumor marker for ovarian CA
CA 125
CA 125 tumor marker
ovarian CA
tumor marker for melanoma
S 100
also in neural crest cell derived like schwanomma
S 100 tumor marker for (3)
melanoma
schwanoma
neural crest cell derived
Alkaline phos tumor marker (3)
pages disease of the bone
METs to the bone
biliary disease
CA 19-9 tumor marker
pancreatic CA
Calcitonin tumor marker
Medullary thyroid CA
2 signals released by tumors to allow angiogenesis
VEGF - vascular endothelia growth factor
bFGF - basic fibroblast growth factor
Common sources of METS - Brain (5)
most common brain CA is METS - 50% (gray/white matter junction
Lots of Bad Stuff Kills Glia
- Lung
- Breast
- Skin (melanoma)
- Kidneys (renal cell)
- GI ( colon CA)
Common sources of METS - Bone (6)
permanently relocated tumors like bone
prostate Renal cell testes/thyroid Lung Breast
Common sources of METS - Liver (5)
Cancer Sometimes Penetrates Benign Liver
Colon Stomach pancreas Breast Lung
Lytic vs blastic METS to the bone
Prostate is blastic
Lung is Lytic
Breast can be lytic or blastic
Cachexia is?
Due to?
profound weight loss - fat and lean muscle
Due to the release of cytokines that raise basic metabolic rate -> (TNF alpha)
3 paraneoplastic effects of small cell carcinoma
ACTH -> cushings
ADH -> SIADH
Ab to presynaptic Ca channels -> lambert eaton
Cushing syndrome due to paraneoplasm
Small cell CA of lung
SIADH due to paraneoplastic (2)
small cell CA of lung
intracranial neoplasm
PTHrP releasing neoplasms (4)
squamous cell CA
renal cell carcinoma
breast CA
head and neck squamous cell
2 and details? (4 subtypes)
Most common cause of hypercalcemia
primary hyperparathyroidism
malignancy is #2
- PTHrP
- hodgkins -> Vit D
- multiple myelinoma -> local osteolytic
- lytic bone mets (breast maybe, Lungs definitely)
Hodgkins lymphoma paraneoplastic syndrome
release active Vit D -> hypercalcemia
Erythropoeitin released from 4 CA
potentially really high hemotocrit
pheochromocytoma
renal cell carcinoma
Hemangiobalstoma
Hepatocellular carcinoma
Lambert Eaton due to?
Characterized by
paraneoplastic disorder of small cell CA of lung where Ab are produced against the presynaptic Ca channels in the neuromuscular junction
Presents similar to myasthenia gravis
differs in that it IMPROVES w/ use
5 most important lifestyle factors affecting CA risk
Smoking Obesity Activity level Diet Sun exposure (esp sun burns early-> melanoma and continued UVB -> squamous cell and basal)
Recommendation for breast CA screening
mammogram q/2 yrs starting age 50
informed age 40
unknown after 75
self breast NOT recommended, Clinical unknown
Cervical CA screening
PAP smear > 21 q 3yrs
> 65 yrs stop
Prostate CA screening
informed 50-75
none after 75
DRE insufficient
PSA not sensitive enough
Colon CA screening
colonoscopy q 10 yrs starting age 50
- start earlier w/ family history 10 yrs before youngest
also have fecal occult blood annually
flex sig q 5 yrs
What immune cell protects from CA cells in the body?
CD8 cytotoxic T cells,
looks for antigens: mutated genes, over expressed proteins, oncogenic viruses, ocncofetal antigens, altered surface glycoproteins (CA125, CA19-9), cell type specific
also NK cells and macrophages
Lung CA screening (NEW 2013)
annual chest CT ages 55-80
- 30 pack yr history
- current smoker or quit w/in last 15 yrs
antineoplastic drugs working in the S Phase of cell cycle
antimetabolites
- methotrexate
- 5 FU
- 6 MP
- cytarabine
Etoposide works in what phase of the cell cycle
G2 and S phase
Vinca alkaloids and taxols work in what part of the cell cycle
the M phase
What cells are susceptible to collateral damage w/ antineoplastics (3)
bone marrow -> hematopoetic
GI tract
hair follicles
all divide rapidly
Methotrexate blocks what enzyme and is used in 3 general situations
folic acid analog -> blocking dihydrofolate reductase which converts DHF-> THF
Used in the syntheses of dTMP thus less DNA made
- cancers - leukemias: ALL/AML. breast , sarcomas
- immune suppression: RA and psoriasis
- Uterine path: ectopic pregnancies, choriocarcinoma, hydradidiform mole
Toxicity w/ methotrexate (3)
myelosuppression - reversible w/ leucovorin
fibrotic lung disease
teratogenic - > neural tube defects
Leucovorin works in what toxicity but not another?
folinic acid rescue in methotrexate
does NOT work in 5 - FU
3 antineoplastic drugs that cause fibrotic lung changes
Bleomycin
Busulfan
methotrexate
Used topically in actinic keratosis and basal cell CA
5 FU
treatment of childhood tumors: Ewing, Wilms and rhabdosarcomas
Dactinomycin - intercalates DNA
Which drugs decrease production of dTMP
5 FU
Methotrexate
Toxicity w/ 5 fluorouracil(2)
Myelosuppression - NOT reversible w/ leucovorin
photosensitivity
Uses of 5 FU(4)
colon CA
pancreatic CA
basal cell CA
actinic keratosis
S cell cycle actor that inhibits DNA polymerase, antineoplastic
Cytarabine
acts as a pyrimidine analog -> leukemia and lymphomas
Purine analogs that inhibit PRPP amidotransferase
Azathioprine
6 mercaptopurine - metab by xanthine oxidase
6 thioguanine - can be given w/ allopurinol
S cycle specific antineoplastic that is metabolized by xanthine oxidase
6 mercaptopurine
6 thioguanine is also a purine analog but does not have increased toxicity w/ the use of allopurinol
Toxicity of 6 mercaptopurie and 6 thioguanine
myelosuppression
hepatotoxicity
Alkylating agents (antineoplatics) (3)
Busulfan
nitrosureas (carmustine, etc.)
cyclophosphamide (ifosfamide)
attaches an alkyl group to DNA -> cross linking of stands making it difficult to divide
Used in brain tumors b/c crosses BBB
risk of what?
nitrosureas - carmustine, lomustine, semustine
risk of CNS toxicity
Cyclophosphamide used in what 2 categories
Solid tumors - testicular, breast, ovarian, leukemia etc..
Immune suppression
- lupes nephritis
- PAN
hemorrhagic cystitis is associated w/ this antineoplastic
rx:
cyclophosphamide, an alkylating agent
Mesna
Mesna is used in what antineoplastic toxicity
hemorragic nephritis due to cyclophasphamide
-> binds to acrolein, the toxic metabolite
covalently cross links DNA at guanine at N-7
Requires bioactivation
cyclophosphamide an alkylating agent
Busulfan toxicity (2)
an alkylating agent
pulmonary fibrosis and hyperpigmentation
Dactinomycin is useful in these 3 tumors
All kids
- Ewings
- rhadomyosarcoma
- Wilms
intercalates DNA
cardiomegaly is the biggest concern w/ these 2 antineoplastics
Rx w?
daunorubicin and doxorubicin
treat w/ dexrazoxane- Fe chelating agent
Bleomycin toxicity
pulmonary fibrosis
an antitumor antibiotic-> free radical formation
Antitumor antibiotics (4)
Dactinomycin
Doxorubicin/daunorubicin
Bleomycin
toxicity of vinblastine
Blasts bone marrow -> myelosuppression
Toxicity of vincristine? (2)
neurotoxicity
peripheral neuritis
Microtubule binding and modulating drugs (5)
vincristine/vinblastine paclitaxel mebendazole/albendazole griseofulvin colchicine
antineoplastic bind to tubin in M phase to block polymerization
vincristine/vinblastine
antineoplastic that hyper stabilizes polymerized microtubules in M phase so mitotic spindle cannot break down
paclitaxel and the like
Toxicity of paclitaxel (2)
myelosuppression
hypersensitivity
Vincristine and vinblastine are used in (4)
hodgkinlymphoma
wilms tumor
Ewing Sarcoma
Choriocarcinoma
Paclitaxels are used for(2)
ovarian and breast Carcinomas
antineoplastics that are nephrotoxic and ototoxic (3)
cisplatin, carboplatin, oxaliplatin
cross link DNA
Cisplatin, carboplatin and oxaliplatin risk?(2)
nephrotoxic and ototoxic
use amifostine to prevent nephrotoxic
Uses of the platens (cisplatin ) (3)
testicular
bladder
ovary
Testicular CA regiment (3)
Eradticates ball Cancer
epotoposide
Bleomycin (ifosfamide)
cisplatin
Anti topoisomerase inhibitors antineoplastics
inhibits topo II
- Etoposide
- teniposide
inhibits topo I
- Irinotecan
- topotecan
Use of etoposide and teniposide (3)
small cell lung
prostate
testicular CA
inhibit topo II
Nephrotoxic and ototoxic drugs (4)
vancomycin
aminoglycoside
loop dieuretics
cisplatin and carboplatin
Uses of Irinotecan
METS Colon CA
inhibits topo I - like topotecan
Uses of topotecan (3)
small cell lung CA
Ovarian CA
cervical CA
inhibits topo 1- like irinotecan
inhibits ribonucleotide reductase -> decreased DNA synthesis in the S cell cycle
Hydroxyurea
Prednisone as an antineoplastic?
may torgger apoptosis
Symptoms of prednisone toxicity ? Alot
BAM CUSHINGOID
Buffalo hump
Amenorrhea
Moon facies
Crazy - agitation Ulcers Skin changes Hypertension Infection Necrosis of femoral head Glaucoma - cataracts Osteoperosis Immune depression Diabetes
SERM used in osteoporosis
agonist and antogonist prop?
Raloxifene
ER agonist in bone
ER antagonist in breast and endometrial
Monoclonal ab against her2 -neu?
What is her2 Neu
trastuzumab
her 2 is a tyrosine kinase
Toxicity with trastuzumab
cardiotoxicity
monoclonal antibody against CD20
ratuximab
used in non hodgkins lymphoma and RA and phemigus vulgarism and ITP and vascultiis
drug acting as a bcr-abl tyrosine kinase inhibitor
imatinib
used in CML