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88 Cards in this Set

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Importance of Glucose-6-phosphate enzyme isoforms?
Clonality can depict neoplasm. Normally you inherit a G6PD isotype from each parent. The ratio of each type should be 1:1. If it's asymmetrical you have a monoclonal growth that can indicate a neoplastic growth. Theoretically any X-linked isoform would work, so if androgen receptors have isotypes you could use those instead. X-linked and thus ONLY WORKS ON WOMEN
B cell clonality determined by Ig light chain phenotype
Ig has 2 heavy, 2 light chains each b cell expresses light chains that are either kappa or lambda
the NORMAL ratio is 3:1 kappa to lambda
any extreme asymmetry from this ratio could indicate neoplasm
3:1 ratio represents?
kappa to lamda KAPPA TO LAMDA KAPPA TO LAMDA 3-1 KAPPA LAMDA
Enlarged lymph node DDx
Metastatic Cancer
Reactive hyperplasia due to infection
Lymphoma

DIAGNOSTIC FOR LYMPHOMA is a Kappa to Lamda ratio that is NOT 3:1
Lamda to Kappa ratio of 3:1 and enlarged lymph node
LYMPHOMA
Kappa to Lamda ratio of 3:1 and enlarged lymph node
NORMAL
Aflatoxin
hepatocellular carcinoma, derived from Aspergillus which can contaminate stored grains
history with a grain silo
Aspergillus, can make aflatoxins which cause hepatocellular carcinoma
Alkylating agents
Leukemia/lymphoma this can be a side effect of chemotherapy
Squamous cell carcinoma of oropharynx and upper esophagus
alcohol
pancreatic carcinoma
alcohol
MCC of hepatocellular carcinoma
alcohol
Carcinogens in cigarette smoke
Polycyclic Hydrocarbons, Arsenic, Naphthylamine
Squamous cell carcinoma of skin risk factor
Arsenic
lung cancer can be caused by this chemical in cigarettes
arsenic
Lung carcinoma
Asbestos This is MORE LIKELY than mesothelioma after asbestos exposure
Mesothelioma
asbestos
Most carcinogenic chemical in cigarette smoke?
polycyclic hydrocarbons
Cigarette smoke causes...
Carcinoma of oropharynx, esophagus, lung AND kidney, bladder due to hyperconcentration of carcinogens in urine.

Also, increases likelihood of cervical cancer.
History of eating large amount of smoked foods with Japanese descent
Think Nitrosamines Stomach cancer, Intestinal type, NOT diffuse
Urothelial carcinoma of bladder
Naphthylamine(cigarette smoke derivative)
What symptom would you expect to see from occupational exposure to Polyvinyl chlorides such as those used to make PVC pipes?
Angiosarcoma of the liver caused by the vinyl chloride exposure
Occupational exposure to Nickel, chromium, beryllium or silica
Lung cancer
Chinese male or indigenous african presenting with neck mass
Nasopharyngeal carcinoma secondary to EBV
Cancer associated with EBV
Burkitt's lymphoma and CNS lymphoma in AIDS patients and nasopharyngeal carcinoma
Older eastern european male and you see a papular erythematous lesion
Kaposi Sarcoma caused by HHV-8 Can also afflict AIDS patients, transplant patients
Which hep viri preclude hepatocellular carcinoma?
Hep B and Hep C Hep B = HepadnavirusHep C = Flavivirus
HTLV-1
HTLV-1 is a retrovirus that predisposed to Adult T-cell leukemia/lymphoma
HPV high risk? low risk?
High risk = 16, 18, 31, 33 (Squamous cell carcinoma of lower GU tract. Also ADENOcarcinoma of cervix) Low Risk = 6, 11 (condyloma acumulatum)
A worker during the japanese nuclear meltdown is predisposed to
ionizing radiation causing AML, CML and papillary carcinoma of the thyroid
What is the malignant cell in AML
myeloblast
What is the MOA of ionizing radiation
generation of hydroxyl free radicals
MOA of non-ionizing radiation
pyrimidine dimers are created which are normally excised by restriction endonucleases
non-ionizing radiation(UVB light) predisposes to....

a/w?
Basal cell carcinoma, squamous cell carcinoma and melanoma of the skin A/W Xeroderma Pigmentosum where base excision is broken.
Most common cancers of INCIDENCE
breast/prostate
lungs
colorectal
Most common cancers of MORTALITY
lung
breast/prostate
colorectal
Mammography looks for which cancer?
DCIS, ductal carcinoma in situ
Where does prostate cancer generally present?
posterior periphery
Describe the RAS pathway
ras-GDP associated with GF in an inactive state
Receptor binding causes GDP to be replaced with GTP activating ras
ras sends growth signals to nucleus
ras inactivated itself by cleaved GTP to GDP.
This is overseen by GTPase activating protein NOW ABNORMALA mutated ras inhibits GTPase activating protein, resulting in its constitutively activation.
Describe role of p53 in DNA repair
p53 is the cell cycle cop It stops a cell in G1 going to S and checks the DNA. If its crappy DNA, it'll say to go get fixed. If it can't get fixed, p53 euthanizes the cell via the Bcl pathway. p53's thug, BAX breaks the Bcl2 that stabilizes the mitochondrial membrane, and thus cytochrome c leaks out and activates apoptotic pathways.
Li-Fraumeni syndrome
germline mutation of one p53 gene.
Rb's role in cell cycle regulation
Rb is bound to E2f, this keeps the cell cycle in G1. When CDK comes over and phosphorylates Rb, E2f falls off and gives the green light for S phase and parties like its 1939. If Rb is mutated, then it is NEVER attached to E2f and the cell ALWAYS has the greenlight to party. That's bad
Germline retinoblastoma is A/w?
osteosarcoma
What gene is overexpressed in follicular lymphoma?
Bcl2. This overstabilizes the mitochondrial membrane, which isn't usually a problem except in the thymus, where you need negative selection to get rid of autoreactive t-lymphocytes. Also B-cells that would undergo apoptosis during somatic hypermutation...don't. This leads to lymphoma, which is probably polyclonal.
Follicular lymphoma is associated with what translocation?
t(14;18) moves Bcl2(18) to the Ig heavy chain locus(14) making it constitutively active
Describe the process of tumor invasion
TUMOR INVASION!!
1.) downregulation of cadherins, which normally keep cells buddy-buddy all attached to each other, causes...well, detachment.
2.) Tumor cells then find a new friend to screw with, laminin, and in the process destroy the basement membrane(type IV collagen) with a collagenase
3.) Bored with laminin, tumor cells attach to fibronectin in the ECM and spread locally until they get tired of THAT.
4.) They find a blood or lymph vessel so they can go explore the world and party....like its 1939.
Sarcoma's generally spread...
haemotogenously
Breast cancers generally spread...
lymphatically(axillary breast node first hit)
omental caking
ovarian carcinoma. Commonly seeds body cavities, like the peritoneum
Hematogenous spread cancers...
Renal cell carcinoma(invades renal vein)
Hepatocellular carcinoma(invades hepatic vein)
follicular carcinoma of the thyroid
choriocarcinoma(placental malignancy)
sarcoma's...DUH
Keratin stains
epithelium
vimentin
mesenchyme
Desmin
muscle
GFAP
neuroglia
neurofilament
neurons
neurons IMF
neurofilament
neuroglia IMF
GFAP
muscle IMF
desmin
Mesenchyme IMF
vimentin
Epithelium IMF
Keratin
S-100
Melanin
What do you look for to be positive in melanoma's?
S-100
Chromogranin
Small cell carcinoma of lung and carcinoid tumors both of those are neuroendocrine tumors
Neuroendocrine tumors
Small cell carcinoma of lung and carcinoid tumors
stains Chromogranin
Absolute definition of benign neoplasm
Will never metastatize
CA-125
ovarian cancer, NON-specific test
Single most prognostic indicator?
metastasis
Grade or Staging more important?
Staging -- TNM
Staging or Grade more important?
Staging -- TNM
PDGFB mutation a/w?
overexpression, autocrine loop that can lead to an astrocytoma
breast carcinoma's can sometimes express this receptor
ERBB2[HER2/Neu] amplification of receptors expressed.
Common treatment for ERBB2 cancers
Trastuzumab
RET function
neural growth factor receptor
RET A/W
MEN 2A, MEN 2B, sporadic medullary carcinoma of thyroid
KIT function?
Stem cell growth factor receptor
KIT A/W
gastrointestinal stromal tumor
RAS gene family A/W
Carcinomas, melanoma and lymphoma
ABL
Tyrosine kinase
ABL A/W
CML and some types of ALL(poor prognosis)
t(9;22) with BCR. Abl starts on 9, but swaps with BCR which is on 22
c-MYC A/W
what translocation?
Burkitt Lymphoma transcription factor
t(8;14) involving IgH which is always on. So when MYC gene on chromosome 8, which is a transcription factor is ALWAYS on, problems arise. In the party factory.
N-MYC
amplification mutation leading to Neuroblastoma
L-MYC
Small cell lung carcinoma
CCND1(Cyclin D1)
What translocation?
Mantle cell lymphoma t(11;14) involving IgH which is always on. So when cyclin, which regulates cell cycle is ALWAYS on, the cops never roll that party.
CDK4 mutation
Melanoma
Growth Factor Receptors
ERBB2[HER2/neu]
RET
KIT
Signal Transducers
RAS gene family - GTP binding protein
ABL - Tyrosine Kinase
Nuclear Regulators
c-MYC
N-MYC
L-MYC

they're all transcription factors
Cell Cycle Regulators
CCND1(Cyclin D1)
CDK4