Random Shit 2024 Flashcards
learn random shit
What anti-angiogenic agent binds angiopoiten 1 and 2?
Trebaninib
(also AMG 386)
Which has highest risk of EOC?
BRIP1
PALB2
RAD51C
RAD51D
RAD51D (10-20%) > RAD51C = BRIP1 (10-15%) >PALB2
What is most radiosensitive in the bone marrow?
Erythrocytes
megalokarocytes
leukocytes
granulocytes
Leukocytes
Framework of the Doctor-Patient relationship
Paternalistic Model: vests majority of decision-making power in the doctor.
Informative Model: vests the majority of decision-making power in the patient. The doctor provides the patient with all relevant information so he/she can made a decision.
Interpretive Model: provides a greater role for the doctor to assist the patient in understanding her values and interests, and the possible impact of different interventions in these terms. The doctor acts as an advisor.
Deliberative Model: the doctor has a role in judging and prioritizing patient values. The doctor indicates both what the patient could do and, in the context of their understanding of the patient’s life and values, what he thinks the patient should do in terms of choice of intervention.
What is the Hayflick limit?
number of times cell divides based on shortening of telomeres
PARPS SPECIFIC SIDE EFFECTS
NIRAPARIB (Zejula): HTN, thrombocytopenia
OLAPARIB (Lynparza): Pneumonitis, transient Cr elevation, anemia or myelosupression
Rucaparib (Rubraca: Liver enzymes elevation, transient Cr elevation interaction w/MATE1/2
CHEK 2 Gene
CHEK2 encodes a cell cycle checkpoint kinase associated with the deoxyribonucleic acid (DNA) damage repair response Fanconi anemia (FA)-BRCA1/2 pathway (upstream of BRCA)
-dsDNA break –> ATM –> CHEK2 –>p53
Breast cancer lifetime risks for frameshift variants: 20 to 40%.
Also associated with 5-10% risk colon cancer
Tisotumab Vedontin (Tivdak)
Antibody-drug conjugate used in recurrent or metastatic cervical cancer. Binds TF.
Tisotumab (a monoclonal antibody against tissue factor) + monomethyl auristatin E (binds to tubulin and microtubules causing microtubule dysregulation and suppressing microtubule dynamics).
Side Effect: Causes severe ocular toxicities (severe vision loss and corneal ulceration). Bleeding risk (epistaxis)
MOA:
1. Tivdak binds to TF-expressing cells
2. The Tivdak-TF complex is internalized and trafficked to the lysosomes
3. MMAE is released from the antibody via proteolytic cleavage
4. MMAE disrupts the microtubule network of actively dividing cells
5. This leads to cell cycle arrest and apoptosis
Insulin and Endometrial cancer
STIMULATE RAS/RAF/MAPK and PI3K/AKT Pathways.
DOWNREGULATE IGFBP.
STIMULATES IGF1 ACTIVITY.
MOA:
Insulin promotes cell proliferation and survival through ACTIVATION OR STIMULATION of the ras–raf –MAPK and PI3K–AKT pathways.
Indirectly, insulin leads to changes in sex hormones, including increased estrogen levels, with ensuing REDUCTION OR INHIBITION in IGFBP1 levels, a negative regulator of IGF1.
The net result of IGFBP1 downregulation is a major INCREASE in IGF1 activity.
2004 study: women with endometrial cancer had lower levels of insulin-like growth factor binding protein-3 (IGFBP-3) than controls.
EGFR Inhibitors
Tyrosine Kinase Small Molecule Inhibitors: Erlotinib and Gefitinib . Bind to tyrosine kinase domain via competitive blockade of ATP binding, blocking EGFR enzymatic activity.
Monoclonal antibodies: Cetuximab and Panitumumab. Bind to the extracellular domain of EGFR and prevent ligand dependent signaling, blocking cell growth and survival signals.
TILS in ovarian cancer
High grade serous OC (HGSOC) has been shown to be more frequently infiltrated with TILs.
Increased levels of CD8+ TILs is positively correlated with OS, not only in HGSOC but also in endometrioid carcinoma.
Increased levels of Treg is associated with a higher death hazard ratio and aggressive type of cancer.
Characteristics of BRCA related breast cancers
BRCA1 tumors: basal-like cancer subtype by gene expression profiling. ER-, PR-, Her2- and are mutant for p53. Mostly invasive ductal carcinoma with medullary features.
BRCA2 tumors: more commonly express ER hormone receptors with approximately 35% being classified as the luminal A subtype (hormone +, her2 neg), and 40% being classified as luminal B (hormone +, her2 +/-, more aggressive).
Mechanisms of resistance to PARP inhibitors
- Restoration of Homologous Recombinations capacity (the most common acquired PARPis resistance mechanism*)
- BRCA reversion mutations restoring protein function
- Stabilization of replication forks
- Increased drug efflux
- Inhibition of PARP trapping and glycohydrolase
- Alteration in cell cycle control (cyclin-dependent kinase 12 and WEE1 are cell-cycle regulators involved in PARPis resistance due to their ability to restore HR)
- Dysregulated signal pathways: upregulation of the PI3K/AKT pathway, upregulation of the ATM/ATR pathway,
Most common type of neoplastic colon polyp
Tubular Adenoma
About 70 percent of all polyps are adenomatous (tubular adenoma), making it the most common type of colon polyp
What cells are CD56 positive?
NK cells