Random Shit 2024

Question 1

What anti-angiogenic agent binds angiopoiten 1 and 2?

Answer 1

Trebaninib

(also AMG 386)

Question 2

Which has highest risk of EOC?
BRIP1
PALB2
RAD51C
RAD51D

Answer 2

RAD51D (10-20%) > RAD51C = BRIP1 (10-15%) >PALB2

Question 3

What is most radiosensitive in the bone marrow?
Erythrocytes
megalokarocytes
leukocytes
granulocytes

Answer 3

Leukocytes

Question 4

Framework of the Doctor-Patient relationship

Answer 4

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.

Question 5

What is the Hayflick limit?

Answer 5

number of times cell divides based on shortening of telomeres

Question 6

PARPS SPECIFIC SIDE EFFECTS

Answer 6

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

Question 7

CHEK 2 Gene

Answer 7

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

Question 8

Tisotumab Vedontin (Tivdak)

Answer 8

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

Question 9

Insulin and Endometrial cancer

Answer 9

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.

Question 10

EGFR Inhibitors

Answer 10

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.

Question 11

TILS in ovarian cancer

Answer 11

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.

Question 12

Characteristics of BRCA related breast cancers

Answer 12

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).

Question 13

Mechanisms of resistance to PARP inhibitors

Answer 13

1. Restoration of Homologous Recombinations capacity (the most common acquired PARPis resistance mechanism*)
2. BRCA reversion mutations restoring protein function
3. Stabilization of replication forks
4. Increased drug efflux
5. Inhibition of PARP trapping and glycohydrolase
6. 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)
7. Dysregulated signal pathways: upregulation of the PI3K/AKT pathway, upregulation of the ATM/ATR pathway,

Question 14

Most common type of neoplastic colon polyp

Answer 14

Tubular Adenoma
About 70 percent of all polyps are adenomatous (tubular adenoma), making it the most common type of colon polyp

Question 15

What cells are CD56 positive?

Answer 15

NK cells

Question 16

Stat Tests:
Paired- parametric, nonparametric
Unpaired-parametric, nonparametric

Answer 16

Paired tests:
Comparing 2 things:
-paired T test (parametric)=Wilcoxon rank (non-para)
Comparing 3+ things:
-ANOVA (parametric) = Friedman (non-para)

Unpaired/Independent:
Comparing 2 things:
-unpaired T/students T (para)=Mann-Whitney U (non-para)
Comparing 3+ things:
-ANOVA (para) = Kruskal-Wallis

ANOVA= analysis of variance

Question 17

Cancers with:
BRCA1
BRCA2

Answer 17

BRCA1: Breast, ovary, male breast, prostate, pancreatic, uterine serous
BRCA2: Breast, ovary, male breast, prostate, pancreatic, melanoma, stomach, GB, bile duct, salivary

Question 18

STIC Management

Answer 18

Per NCCN:
1) observation alone with or without CA-125 testing when no evidence of invasive cancer is noted
2) surgical staging with observation or chemotherapy based on NCCN Guidelines if invasive cancer is noted.

For those without prior genetic counseling and/or testing, discovery of a STIC should prompt a genetics evaluation.

It is not clear whether surgical staging and/or adjuvant chemotherapy is beneficial for those with STIC

Question 19

Immune Escape Mechanisms

Answer 19

1. Downregulate MHC
2. Tumor Ag loss
3. Stimulate inhibitory receptors on T cells (CTLA-4, PD1, LAG3) this was answer option
4. overproduce indoleamine 2,3 deoxygenase
5. increase tumor infiltration by Tregs and NKT cells to limit immune destruction

Question 20

Warfarin reversal options

Answer 20

Vit K (takes time)

Immediate=FFP and prothrombin complex concentrate

Question 21

Shock types and associated changes

Answer 21

Question 22

Emetogenic Drugs

Answer 22

Highly Emetic > 90%: Cisplatin, Cyclophosphamide, Anthracyclines

Minimally Emetic < 10%:
Bev
Bleo
Nivo/Pembro
Trastuzumab
Vincas

Question 23

Leukemogenic Chemos

Answer 23

Melphalan (10%), Etoposide (1%), Cisplatin, Cyclophosphamide (<1%)

5-FU low leukemogenic potential

Question 24

Lynch Syndrome cancer risks by mutation

Answer 24

MLH1 - 30-50% risk EC (4-20% Ovary)(46-60% colorectal, highest)
PMS2 - 13-25% risk EC (1-3% ovary) (8-20% colorectal, lowest for all)
MSH2 - 20-50% risk EC (8-38% ovary, highest) (33-52% colorectal)
MSH6 - 16-50% risk EC (1-13% ovary)(10-40% colorectal)

Question 25

K and Ca EKG Changes

Answer 25

Question 26

Dopamine Doses and Effects

Answer 26

LOW DOSE (0.5 to <2 mcg/kg/min):
- Mainly activates DOPAMINE-1
receptors in the renal, mesenteric, cerebral and coronary beds resulting in selective vasodilation and increasing blood flow.

INTERM DOSE (5 to 10 mcg/kg/min):
- stimulates BETA-1 adrenergic receptors and increases CO, by increasing SV with variable effects on heart rate.

HIGH DOSE (> 10 mcg/kg/min):
- Stimulate alpha-adrenergic receptors and produce vasoconstriction with an increased SVR.

Question 27

Imatinib (Gleevec) MOA

Answer 27

• Small molecule inhibitor targeting multiple tyrosine kinases such as:
  CSF1R, ABL, c-KIT (through RAS/RAF/MEK pathway) and PDGFR-β
• Specifically used to treat CML and ALL that are Philadelphia chromosome positive t(9;22)(q34;q11).
• Also treats (GIST) > KIT positive
• Side effects: gastrointestinal symptoms, musculoskeletal and skin reactions, bone marrow suppression (neutropenia/thrombocytopenia), fluid retention

Question 28

Ethics Principles

Answer 28