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60 Cards in this Set
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Bevacizumab (Avastin)
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(Targeted therapy)
o Anti-VEGF monoclonal antibody. o Binds to VEGF causing reduction in tumor angiogenesis |
o Beneficial when used in concert with chemotherapy
o Used for met. Breast, colon, renal cancer |
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Cisplatin
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(chemotherapy)
o Platinum introduced into DNA o Causes damage that fast-dividing cells cannot fix readily but normal cells can. |
o Fast dividing cells
o Testicular cancer |
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Cyclophosphamide/
Ifosphamide |
hemotherapy)
o Prodrug—effective once metabolized o Alkylating |
o Anti-cancer
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5-FU
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(chemotherapy)
o Works as a nucleoside analogue competing with Uridine causing no thymidine precursor |
o Anti-cancer
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Methotrexate
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(Chemotherapy)
o Disrupts pyrimidine synthesis via impaired folate production -------- Inhibits dihydrofolate reductase (DHFR). Folic acid analog 1. Increases release of adenosine – energy sap 2. Decreases activity of cytokines 3. Anti-angiogenic |
o Anti-cancer
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Paclitaxel
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Chemotherapy)
o Anti-microtubule. Causes stabilization of the metaphase place |
o Anti-cancer
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Doxorubicin
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(Chemotherapy/antibiotic)
o Interferes with toipiosomerase II causing decrease in torsional strength of DNA |
o Anti-cancer
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Topotecan/Irinotecan
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(Chemotherapy)
o Prevents re-ligation of DS breaks after torsional break o S-phase specific |
o Anti-cancer
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Imatinib (Gleevec)
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(Targeted therapy)
o Inhibition at the ATP-binding site of TK o Inhibits BCR-ABL signal transduction o Only effects Hematopoetic cells |
o Used in BCR-ABL (Philadelphia chromosome cancers)
o Use in CML, CIST, PDGF, and c-KIT disorders |
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Sorafenib
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(Targeted therapy)
o Prevents cell proliferation and angiogenesis |
o VEGF and BRAF as target
o Used in hepatocellular carcinomas |
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Trastuzumab (herceptin)
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(Targeted therapy)
o HER and HER2 receptor as target o Prevents ligand binding in those that overexpress HER2 |
o Breast cancer
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IFN
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(Immune modulator)
o Interacts with surface cell proteins causing suppression of cell proliferation o Macrophage activation |
o Anti-cancer
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Tamoxifen
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(targeted)
o Estrogen antagonist |
o Anti-cancer
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RADIATION
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• Radiation of photons, electrons, or protons
• Radiation causes a hydroxyl radical (a radical intermediate) • If you have oxygen that can pair with the free radical, DNA damage results • DS DNA breaks cause permanent damage to fast tumors 2 Kinds of Delivery: 1) External 2) Internal, Brachytherapy: via catheters 3 Kinds of therapy: 1) Photons: INSERT FURTHER DETAILS 2) Electrons 3) Protons May be used in conjunction with chemo. Mindful of TI. |
Delivery:
• Linear acceleration of 8-11 MeV or proton therapy • SI unit in gray (20-80 gray) • Delivered Mon-Fri in small amts. (due to Reassortment, ReOx, repair, repop) • Hypo/Hyperfractionation (less often for delivery or more regularly) Curative for: Neck cancer, lymphoma, GI cancer, cervical cancer. May also be neoadjuvant or adjuvant with surgery. Used for: keloids, ossicifcation, large tumors, lymphoma, trigeminal neuralgia |
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Unfractionated Heparin
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Inactivates serine proteases by binding to AntiThrombin 3 (AT3) and Thrombin
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o Administered via IV or SQ
o IV administered o Indication: - Acute arterial and venous thromboembolism - Prevention of thromboembolisms - Maintenance of coronary artery bypass grafts |
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LMW Heparin :
Nadroparin (Fraxiparin) Tinzaparin (Logiparin) Enoxaparin (Clexane) Dalteparin (Fragmin) |
Inactivates serine proteases by binding to AntiThrombin 3 (AT3) and Factor Xa
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o ½ life is longer so dosing is done by weight
o SQ 1-2 times per day o Indication: - Acute arterial and venous thromboembolism - Prevention of thromboembolisms - Prevention ischemia following MIs |
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Direct Thrombin Inhibitors
Lepirudin Argatroban Dibigitran |
Lepirudin: found originally as anti-coag of leeches
Binds to Thrombin directly |
o Use for HIT
o Lepirudin: renal excretion o Argatroban: kidney excretion o Dabigitran: Renal excretion and PO (but not yet approved) |
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Direct Factor Xa inhibitors
Rivaroxiban Apixaban Fondaparinux |
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o Rivaroxiban is PO
o Apixaban is PO → may be used to prevent clots in the future |
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Coumadin/Warfarin
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o Vitamin K is used to build the GLA domain in factors 2,7,9,10 and Protein C
o Coumadin prevents recycling of Vit K o Warfarin is metabolized in liver o May be reversed with Vit K |
o PO
o Typically 2.5-5mg daily dose o Used for venous and rarely arterial thombosis prevention + heart valves, DVT prevention o Dose via INR |
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Plasminogen Activators
Streptokinase Urokinase t-PA |
Plasminogen, once converted to plasmin (via t-PA) aids in the break-down of fibrin clots into D-dimers. Up-regulation of plasmin causes breakdown of clots
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Indication:
- Acute MIs - PEs - DVTs |
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Prostaglandins
PGE1 / PGE2 (EP1-4) |
o Cytoprotection in GI by inhibition of gastric acid (COX1)
o Regulate renal blood flow (COX1/2) o Regulate Na+/H2O (COX1/2) o Induce uterine contraction (COX1/2) o Pyrogenic & Pro-inflammation (COX2) On inflammation: pain, redness, heat, swelling (E2) |
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Prostaglandins
PGF2α (FP) |
o Vascular smooth muscle contraction (COX1/2)
o Uterine contraction (COX1/2) o Luteal regression o Vasoconstrictor On inflammation: swelling |
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Prostacyclin I2 (PGI2) (IP)
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o Main PG synthesized by endothelial cells by COX2
o Inhibits platelet aggregation o Vasodilation o Inhibits smooth muscle proliferation o Proinflammatory On inflammation: pain, redness, swelling |
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Thromboxane (TxA2)
(TPα or β) |
o Produced by M0s, platelets (only COX1), and kidney
o Platelet aggregation o Vasoconstriction o Smooth Muscle Proliferation |
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COX1
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Expression
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Constitutively active (can be upregulated slightly w/ inflammation)
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COX1
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Function
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housekeeping functions
Cytoprotective PGs in GI tract |
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COX1
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Distribution
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Broad, but only form in platelets
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COX1
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Regulation
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Very Little
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COX2
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Expression
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Upregulated 2o to inflammation
(some baseline level) |
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COX2
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Function
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Upregulated by cytokines, growth factors
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COX2
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Distribution
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Kidney, brain, synovial cells, M0s, predominant in endothelial cells
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COX2
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Regulation
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mRNA regulated by glucocoritcoid
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Carbaprost
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PGF2α analogue
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Mid-trimester abortions
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Prostin E
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PGE2 analogue
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Mid-trimester abortions
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Misoprostol
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PGE1 analogue
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Abortifacient in early pregnancy, Patients on NSAIDS at risk for peptic ulcer
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Dinoprostone
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PGE2 analogue
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Labor induction
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Alprostadil
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PGE1 analogue
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Impotence, patent ductus arteriosis
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Epoprostenol
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PGI2 analogue
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Primary pulmonary hypertension
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Aspirin
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Irreversiably binds COX (1&2)
Acetylates Ser in active site |
Low Dose – inhibits platelet COX1 – antiplatelet
High Dose – analgesic & anti-inflammatory |
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Ibuprofen
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Reversibly bind COX (1&2)
Phase II metabolism |
Antipyresis (block PGE1/E2)
Analgesic (PGE1/2, PGI2) Anti-inflammaotry Antiplatelet (esp aspirin) |
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Naprocin
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Reversibly bind COX (1&2)
Phase II metabolism |
Antipyresis (block PGE1/E2)
Analgesic (PGE1/2, PGI2) Anti-inflammaotry Antiplatelet (esp aspirin) |
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Coxibs
(Rofecoxib, celecocib) |
Selectively inhibit COX2
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Antipyresis (block PGE1/E2)
Analgesic (PGE1/2, PGI2) Anti-inflammaotry Antiplatelet (esp aspirin) |
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Acetaminophen
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NOT AN NSAID
Minimally inhibits COX at typical dose |
Analgesic
Antipyretic LITTLE anti-inflammatory activity NO effect on platelet function |
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Glucocorticoids
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Made in Zona Fasiculata of adrenal cortex.
Controlled by ACTH released from h.t |
Regulate immune and metabolic function
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predisone
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o Receptor in cytosol stabilized by Hsp90,56 binds GC → loses Hsps & localizes to nucleus → binds to GRE on DNA → Transcriptional effects
o Interaction with NK-kB inhibts IL6/8 production o Increased expression of lipocortin which downregulates sPLA2 |
Metabolic: gluconeogenesis, lipolysis, lipogenesis (insulin)
Catabolic: (esp at supratherupeutic doses) protein, osteoporosis, wasting *Immunosuppressive: CELL mediated immunity, proliferation of WBCs *Anti-inflammatory: Inhibit PLA2, Decrease COX(2) mRNA, Decrease IL2,3, cytokines, T-cell proliferation and function Other: Na+ homeostasis, behavioral effects With Rx want to maximize anti-inflammatory effect and minimize Na+ retention effect (hypertension) |
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Cyclophosphamide
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o Alkylating agent
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o Destroys proliferating T and B cells
o Can also destroy resting cells |
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Methotrexate
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o Inhibits purine synthesis
o Inhibits folate dependent enzyme |
o Inhibits all rapidly dividing cells
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Azathioprine (Imuran)
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o Inhibits de novo purine synthesis
o Inhibits hypoxanthine-guanin phosphoribosyltransferase o Metabolism dependent on xanthine oxidase |
o Inhibits all rapidly dividing cells
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Mycophenolate (Cellcept)
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o Inhibits purine synthesis
o Inhibs inosine monophosphate dehydrogenase – needed for guanine nucleotide synthesis |
o Prevents proliferation of B and T cells
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Sirolimus (Rapamycin)
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o Inhibits kinase mTOR
o Blocks signaling in T-cells = cell cycle arrest o Forms a complex with FKBP12 blocks mTOR – used in IL2 signaling |
o Prevents T-cell activation & proliferation
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Cyclosporine / Tacroliumus
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o Binds to immunophyllin → binds to calcinueurin → inhibits its phosphatase activity
o W/out calcinueurin NK-kB stays phosphoralated and can’t locate to nucleus o Nk-kB usually regulates IL2, GM-CSF, TNFα, IFNγ |
o Inhibits IL2 mediated T-cell response
o Prevents T-cell proliferation o Kidney transplant |
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Polyclonal Antibodies
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o Anti-lymphocyte Globulin (ALG)
o Anti-thymocyte Globulin (ATG) o Bind to range of molecules on cells including T-cells |
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Monoclonal Antibodies
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o More specific
o Targeted at T-cell antigens o Ex: o Anti-CD3 – blocks antigen recognition, proliferation, signaling, promotes T-cell opsonization and deletion o Anti-CD25/IL2R antagonist (daclizumab/basiliximab) – block T-cell activation o Anti-TNFα (infliximab) – blocks TNFα binding used for RA and Crohn’s |
Autoimmune, transplant
-ximab: chimeric -zumab: humanized -umab: fully human -cept: receptor fusion |
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Abatacept
CTLA4Ig |
Binds to CD80/86 (B7) on APCs blocks costimulation → antigen specific T-cell anergy
1. inhibits humeral immune response (transient effects) 2. Inhibition of cytokine secretion by T-cells |
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Rituximab
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Fab portion binds CD20 (important for activation and growth) on B-cells Fc portion mediates lysis through complement or antibody
1. Prevents TNFa, IL6 release from B-cells 2. Prevents B-cells from activated T-cells 3. Prevents plasma cell formation and antibodies |
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Leflunomide
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Pyrimidine antagonist / anti-proliferative. Largest impact on T-cells
Also energy sap |
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Anti-TNFα
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Blocks TNFα
1. As its transmembrane bound 2. Soluble 3. Bind to receptor (Aalimumab,Golimumab,Infliximab,Etanercept,Certolizumab) |
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Tocilizumab
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Blocks transmembrane and soluble IL6 (pro-inflammatory cytokine)
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Anti – NF-kB
(under study) |
o Anti-lymphocyte Globulin (ALG)
o Anti-thymocyte Globulin (ATG) o Bind to range of molecules on cells including T-cells |
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JAK Inhibitors
(under study) |
IL2,4,7,9,5,21 all go through JAK signalling
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