zwinthrop's version from 2015-05-18 18:27

Renal Cancers

Question Answer
Renal CarcinomaMNEMONIC: 3 letters = Chromosome 3 = Triad (hematuria, flank pain, mass).
GENERAL: Most common primary renal malignancy. RISKS: Men 50-70, Smoking, Obesity, HTN.
GENETICS: Loss of VHL (3P) Tumor Suppressor --> Increased IGF-1 --> Increased HIF --> Increased VEGF/PDGF
Clear Cell Carcinoma = 70-80%, originates in PCT, polygonal clear cells filled with lipids/carbs, more sporadic than familial (5%). VHL Syndrome associated.
Papillary Carcinoma = 10-15%, Originates in DCT, cuboidal/low columnar cells, papillary growth, foam cells in papillary cores, Psammoma bodies, associated with Trisomy 7/17 and loss of Y chromosome.
CLINICAL: Edema (varicocele due to blocked drainage of spermatic vein (left kidney)), Paraneoplastic syndromes: EPO (polycythemia), Renin (HTN), PTHrp (hyper Ca2+), ACTH (Cushing syndrome). Metastasis to lung/bone.
STAGING: based on involvement of renal vein invasion (IVC/hematogenous spread).
Urothelial CarcinomaMNEMONIC: Problems in your Pee SAC: Phenacetin, Smoking, Aniline dyes, Cyclophosphamide.
Genetics: P53, RB, Lynch Syndrome.
TYPES: Transitional Cell Carcinoma = most common tumor of urinary tract (renal calyces, pelvis, ureters, bladder), painless hematuria.
RISKS: Schistosoma haematobium infection (Middle East), chronic cystitis, smoking, chronic nephrolithiasis. Presents with painless hematuria.
CLINICAL: Hematuria, Palpable Hydronephrosis/flank pain, Bilharziasis, Proximal Urethra, Bad Prognosis.
Wilms TumorGENERAL: most common renal malignancy in children 2-4 (90% sporadic). GENETICS: Loss of function mutations of tumor supressors.
TYPES: WT1 = WAGR Complex (Wilms, Aniridia, Genitourinary malformation, mentar retadation)-11p13 del; Denys-Drash Syndrome (90% risk for Wilms). WT2 = Beckwith-Wieldemann Syn (Wilms, Macroglossia, Organomegaly (tongue), Muscular Hemihypertrophy).
CLINICAL: Large, palpable unilateral flank mass and/or hematuria, HTN (renin).
HISTO: blastema, primative glomeruli, tubules, and stromal cells. Blastema: blue cells. Triphasic Combination. Anaplasia determines prognosis

Renal Cancer Drugs

Question Answer
All nibs→ inhibit PDGFR/VEGF and cause Hand-foot syndrome, also called Palmar-Plantar Erythrodysesthesia.
What is Hand-foot syndrome? What is it a SE for? Side effect of some types of chemotherapy. Hand-foot syndrome causes redness, swelling, and pain on the palms of the hands and/or the soles of the feet.
SunittinibMOA: Multi-kinase inhibitor - inhibits angiogenesis/prolif (PDGFR/VEGF ).
SE: neutropenia; thrombocytopenia; hypertension; diarrhea; hyperamylasemia; hand-foot syndrome (palmar-plantar erythrodysesthesia).
SorafenibMOA: Multi-kinase inhibitor - inhibits angiogenesis/prolif (PDGFR/VEGF ).
SE: rash; diarrhea; hand-foot syndrome).
PazopanibMOA: kinase inhbitor (VEGF 1/2/3;PDGF-α/β; c-KIT; FGF-1/3)
AxitinibMOA: newest kinase inhbitor (VEGF 1/2/3;PDGF-α/β; c-KIT).
TemsirolimusMOA: mTOR inhibitor -- downstream inhibits HIF. Esterified precursor of sirolimus.
SE: Rash; Pain; infection; edema; thrombocytopenia; neutropenia; hyperlipidemia; hyperglycemia.
EverolimusMOA: mTOR inhibitor -- downstream inhibits HIF. Esterified precursor of sirolimus.
SE: Stomatitis; Infections; Fatigue; Asthenia; Cough; Diarrhea.
BevacizumabMOA: VEGF inhibitor - soaks up ligand so it cannot bind VEGFR2 - stops proliferation/angiogenesis. BIG POINT:: only attacks VEGF pathway, not PDGF-beta, but does stil lcompletely block VEGF.
SE: asthenia, pain, infection.
IL-2MOA: activates lymphoid cells→ T-cell growth factor that activates T-cells and natural killer cells. Short half-life.
SE: fluid retention, inflammation, hypotension, arrythmias.
IFN-alpha 2aMOA: antiproliferative effects on RCCs.
Why are RCC's resistant to chemo?MDR p-glycoprotein (ATP-pump). Renal proximal tubules and renal cell carcinoma express high levels of the MDR protein→ Generally < 10% success rate
Temsirolimus works by binding to FKBP12 and subsequently inhibiting what protein(s)?mTOR
Stage IV RCC is aggressively treated with agents such as sunitib, sorafenib, and bevacizumab that ultimately target what aspect of the disease?Angiogenesis and proliferation
Historically, advanced stage renal cell carcinoma has had a bleak prognosis because the disease is resistant to traditional cancer chemotherapeutics (alkylating agents, antimetabolites, and natural products) The primary reason for this resistance isHigh expression of the multi-drug resistance pump
Can you describe - in a sentence - the difference b/w tacrolimus and everolimus?Calcenuerin inhibitor vs. mTOR inhibitor

Transplant Rejection Drugs

Question Answer
CyclosporineGoal: Maintenance. MOA: Block Calcineurin→ blocks T cell activation and apoptosis
TacrolimusGoal: Maintenance. MOA: Binds FKBP→blocks Calcineurin→ blocks T cell activation and apoptosis.
SirolimusGoal: Maintenance. MOA: Blocks TOR→permits apoptosis/blocks T cell activation
AzathioprineGoal: Maintenance. MOA: Block DNA synthesis via purine metabolism (BM issues with Allopurinol)
Mycophenolate mofetilGoal: Maintenance. Block DNA synthesis by blocking IMPDH
PrednisoneGoal: Induction , Maintenance, & Anti-Rejection. MOA: Blocks Cytokine Expression; Prevent all phases of T cell activation
BasiliximabGoal: Induction. MOA: Blocks IL-2 Receptor→Blocking T cell expansion
rATG (Thymoglobulin®)Goal: Induction. MOA: Destroys Cells via CD3
RituximabGoal: Anti-Rejection. MOA: Anti-CD20 monoclonal antibody (mouse); Destroys naïve and resting memory B cells