FMS Weeks 6 & 7 Flashcards
Pathology
What are ERBB1 and ERBB2?
EGFR and HER growth factor receptors
What neoplasias are Actinomycin D used for?
choriocarcinoma, Wilm’s tumor, testicular tumors, Kaposi’s sarcoma
What type of tumors are steroid hormones used in?
HR+ tumors
What type of drug is Mechlorethamine?
alkylating agent
What are the 5 big tumor suppressor genes?
P53, RB, APC, PTEN, CDH1
What typ of drug is Bortezomib?
Proteosome inhibitor
What are the 6 hallmarks of cancer?
SERIE A
SUSTAINING proliferative SIGNALING
EVADING growth SUPRESSORS
RESISTING cell DEATH
INDUCING ANGIOGENESIS
ENABLING replicative IMMORTALITY
ACTIVATING INVASION/METASTASIS
What type of drug is danazol?
Androgen agonist
What is the target of Bevacizumab?
VEGF
What type of drug is Lenalidomide?
angiogenesis inhibitor
what is desmoplasia?
firm abundant collagen in many malignant tumors
characteristics of coagulative necrosis
gross architecture is preserved, firm texture, all organs except the brain
What does the tissue in this slide display?
coagulative necrosis
What is the mechanism of fat necrosis?
Leaking digestive enzymes (such as lipases from the pacreas) destroy cells, causing fatty deposits through saponification, calcium deposits, and inflammatory reaction
How do tumors enable replicative immortality?
upregulated telomerase activity
What are the typical toxicities of bleomycins?
skin lesions, hyperpigmentation, dose-limiting pulmonary fibrosis
What is the mechanism of topoisomerase inhibitors?
bind to DNA/topoisomberase II and stabilize dsDNA; results in double stranded breaks
What is type C Niemann-Pick?
lysosomal storage disease; mutations affecting enzyme in cholesterol trafficking
what are renal tubule resorbtion droplets?
reversible accumulations of protein that are absorbed into the cytoplasm of proximal tubular cells; seen in proteinuria conditions
What are the toxicities of lenalidomide?
severe neutropenia, thromboembolism
What type of drug is Trastuzumab?
Monoclonal anitibody
What are the main causes of hemosiderosis?
overload of iron: increased dietary absorbtion, hemolytic anemias, repeated blood transfusions
What is the mechanism of antineoplastic alkaloids?
disaggregate mitotic spindles (metaphase arrest)
What type of drug is Paclitaxel?
taxane
What type of drug is tamoxifen?
Estrogen antagonist
What kind of drug is Nivolumab?
monoclonal antibody (checkpoint inhibitor)
describe metastatic calcification
less common; otherwise normal tissues; associated with hypercalcemia and or some abnormality in Ca metabolism
What does the tissue in this slide display?
liquifactive necrosis
what are the toxicities of Bortezomib?
Therapeutic index around 1; peripheral neruopathy, hypotension, GI, asthenia, myelosuppression
What type of drug is Irinotecan?
topoisomerase inhibitor
With what type of necrosis is pus associated?
liquefactive
What type of drug is 6-mercaptopurine?
Purine analog
Use of retinoic acid in neoplasias?
high concentrations stimulate repressed (broken) RA receptors; especially in myelocytic leukemia (APL)
How does proteasome inhibition work?
they block the proteasome, producing conflicting regulatory signals; cancer cells are more sensitive to proapoptotic effects and undergo apoptosis more than normal cells
Mechanism of purine analogs as antineoplastics?
prodrug that inhibits ATP/GTP synthesis
what are the types of necrosis?
coagulative, liquefactive, caseuous, fat necrosis, and fibrinoid necrosis
What kind of drug is this?
Alkylating agent (mechlorethamine); nitrogen mustard
How do aromatase inhibitors work?
Inhibit aromatase (used in estrogen production); used in combination with estrogen inhibitors like tamoxifen for ER+ tumors
What type of drug is Leuprolide?
GnRH agonist
What is a fibroadenoma?
benign, biphasic (fibroblasts&glandular) neoplasm of the breast
what are the toxicities of vinblastine?
MYELOSUPPRESSION, peripheral neuropathy
What type of drug is Pomalidomide?
angiogenesis inhibitor
What type of drug is Degarelix?
GnRH antagonist
What is hemosiderin?
an endogenous pigment derived from hemoglobin, seen in tissues of both physiological/pathological blood cell breakdown
what are the main causes of metastatic calcification?
hypercalcemia: increased secretion of PTH, increased bone resorbtion, vitamin D disorders, renal failure
What is the classical toxicity of Thalidomide?
teratogen, peripheral neuropathy
What is the classical toxicity of checkpoint inhibitors?
immune suppression
What type of drug is Dactomycin?
Antineoplastic antibiotic
What is the philadephia chromosome?
a t(9,22) that leaves ABL gene (Bcr-Abl TK) constituativelyl activated
what is the limiting toxicity of cisplatin?
nephrotoxicity
What are “-tinibs”?
kinase inhibitors
What is unique about Bleomycins?
inactivated except in skin and lung tissue (does not suppress bone marrow)
what are asbestos bodies?
deposition of calcium and iron salts on asbestos fibers
What type of drug is Pertuzumab?
monoclonal antibody
what is Bevacizumab used for?
colon cancer and vasculopathy of the eye
What type of drug is cyclophosphamide?
alkylating agent
what are “-mabs”?
monoclonal antibody drugs
What is KRAS?
G protein
what are the toxicities of Actinomycin?
Classical antineoplastic toxicities
What is steatosis?
fatty accumulation/change in cells that are not able to package/process triglycerides
Key aspects leading to irreversible cell injury?
inability to correct mitochondrial dysfuntion and major disturbances in membrane function
What are the toxicities of pyrimidine analogs?
classical, CNS and MYELOSUPPRESSION, GI, skin
What are Psammoma bodies?
dystrophic accumulation of calium layers with a lamellated appearance
What is the antineoplastic mechanism of taxanes?
mitotic spindle inhibitors; stabilizes microtubules leading to metaphase arrest
How do antineoplastic antibiotics work?
Intercalation and generation of free radicals causing DNA damage (also transcription and replication inhibition at high doses)
what is a leiomyoma?
a benign tumor of the smooth muscle
What is alpha 1 anti-trypsin deficiency?
an accumulation of abnormal endogenous proteins (partially folding) in the ER of liver cells; circulating enzyme deficiency causes emphysema
What type of drug is Adriamycin?
antineoplastic antibiotic
What type of drug is Etoposide?
topoisomerase inhibitor
what is Bortezomib typically used for?
multiple myeloma and mantle cell lymphoma
What type of drug is Nivolumab?
monoclonal antibody
What type of drug is Bevacizumab?
monoclonal antibody; angiogenesis inhibitor
What type of drug is Vorozole?
Aromatase inhibitor
What type of drug is Letrozole?
aromatase inhibitor
What type of drug is Ipilimumab?
monoclonal antibody
What type of drug is Vincristine?
vinca analog
What type of drug is imatinib?
Tyrosine Kinase Inhibitor
What are the main toxicities of Trastuzumab?
CARDIOTOXICITY
long half life; rigors, cytokine release syndrome, tumor lysis syndrome,
What type of drug is Cisplatin?
platium analog
What are the toxicities of Adriamycin (Doxorubicin)?
Classical toxicities and CARDIOTOXICITY
Why do tumors need to enable angiogenesis?
they outgrow their blood supplies
Describe tyrosine kinase inhibitors?
“-tinibs”; inhibit tyrosine kinases associated with neoplasias, metabolized by CYP3A4 (common drug interations), hard to predict toxicities
What is the typical example of fibrinoid necrosis?
“immune complexes” and fibrin deposited on the walls of blood vessels
What are the 2 features of reversible cell injury seen in light microscopy?
cell swelling and fatty change
What type of drug is docetaxel?
taxane
What are the toxicities of Paclitaxel?
myelosuppression, peripheral neurophathy, cardiac block and arrythmias
what are “-rafenibs”?
raf kinase inhibitors
What type of drug is retinoic acid?
Vitamin A
What is the mechanism of cyclophosphamide?
activated to reactive carbocation (carbonium) by CYP450s; given near tumor site, creates adducts across DNA strands
what is VEGF associated with?
angiogenesis regulation
What is Thalidomide used for as an antineoplastic?
multiple myeloma and other malignancies
What type of drug is Flutamide?
androgen antagonist
What is the angiogenesis action of thalidomide?
inhibits VEGF and bFGF
What are the two components of tumors?
parenchyma (neoplastic cells ) and reactive stroma (connective tissue)
What does Bortezomib act on?
inhibits ubiquitin-proteosome pathway (26S inhibitor)
How do platium analog antineoplastics work?
they crosslink DNA
What are the toxicities of alkylating agents?
classical neoplastic toxicities; purine crystalluria
cyclophosphamide: hemorraghic cystitis
Busulfan: pulmonary fibrosis
What type of drug is Carfilzomib?
proteosome inhibitor
What are the toxicities of topoisomerase inhibitors?
SECONDARY LEUKEMIA (AML), bone marrow suppression, hepatic
What are the toxicities associated with TK inhibitors?
multiple hard to predict toxicities (skin reactions, hepato, hypertension, myelosuppression, edema, CHF)
What is the classic example of caseous necrosis?
lung tissue in tuberculosis
What are “-zomibs”?
proteasome inhibitors
What are glycogenoses?
glycogen storage diseases; defective enzymes in synthesis/breakdown of glycogen, causes cell injury/death
Where does trastuzumab act?
HER2-EGFR protein
what is a rhabdomyosarcoma?
a malignant tumor of the striated msucle
what are “-anibs”?
angiogenesis inhibitors
What are the toxicities of 6-Mercaptopurine?
MYELOSUPPRESSION
classical toxicities, hepatotoxicity, inhibition of xanthine oxidase (necessitates dose reduction with allopurinol)
What type of drug is Gefitinib?
Tyrosine Kinase Inhibitor
What type of drug is Thalidomide?
angiogenesis inhibitor
how might a cell adapt to ER stress from misfolded proteins?
decreased protein synthesis and increased chaperone production; otherwise apoptosis
What is anaplasia?
poorly differentiated
What are xanthomas?
accumulation of foamy macrophages in connective tissue
what are russell bodies?
distended ER in areas of chronic inflammation (plasma cells active synthesizing immunoglobulins)
What type of drug is Vinblastine?
Vinca alkaloid
What are the toxicites of vincristine?
PERIPHERAL NEUROPATHY, myelosuppression
What type of drug is Actinomycin D?
Antineoplastic antibiotic
What is the difference between GnRH agonists and antagonists?
GnRH antagonists are better drugs because they cause drop in LH and FSH without initial surge (GnRH agonists cause initial surge in LH & FSH as receptor numbers increase; require androgen/estrogen antagonists concurrently)
What type of drug is Erlotinib?
Tyrosine Kinase Inhibitor
What category would best descrive glycogen storage diseases?
Accumulation of abnormal endogenous substance due to genetic or acquired defects
What are the immunomodulatory activities of thalidomide?
T-cells are stimulated; B-cells undergo apoptosis
What type of drug is estradiol?
estrogen agonist
two types of pathologic calcification?
dystrophic and metastatic
How do monoclonal antibodyies work?
They are mediators of receptor blockades and antibody-dependent cellular toxicity (driving apoptosis)
What type of necrosis is most associated with the central nervous system?
liquefactive
What is NMYC?
a trascription activator
what is an infarct?
a localized area of coagulative necrosis
What type are Pompe disease and von Gierke disease?
glycogen storage disorders
What is BRAF?
RAS signal transducer
What is the effect of the Philadelphia chromosome?
constituatively activated TK ABL
What type of drug is 5-Fluorouracil?
pyrimidine analog
What phenomenon is featured in this slide?
artherosclerosis
What is a leimyosarcoma?
a malignant (mesenchymal) tumor of the smooth muscle
How to ‘classical’ antineoplastics work?
they inhibit nucleic acid synthesis: binding to DNA or interfering with nucleic acid pathways
describe dystrophic calcification
more common type of calcification; locally in dying/abnormal tissue (also breast tissue); normal serum levels and calcium metabolism
What type of drug is Bleomycin?
antineoplastic antibiotic
