Incazelo

I-Lenalidomide (CC-5013) iphuma ku-Thalidomide kanye ne-immunomodulator esebenzayo ngomlomo. I-Lenalidomide (CC-5013) iyi-ligand ye-ubiquitin E3 ligase cereblon (CRBN), futhi ibangela ukukhetha kwendawo yonke kanye nokucekelwa phansi kwezinto ezimbili ze-lymphoid transcription factor, i-IKZF1 ne-IKZF3, nge-CRBN-CRL4 ubiquitin ligase. I-Lenalidomide (CC-5013) ivimbela ngokuqondile ukukhula kwama-B-cell lymphomas avuthiwe, okuhlanganisa i-myeloma eminingi, futhi yenza ukukhululwa kwe-IL-2 kumaseli T.

Ingemuva

I-Lenalidomide (eyaziwa nangokuthi i-CC-5013), okuphuma ku-thalidomide ngomlomo, i-antineoplastic ejenti ebonisa umsebenzi we-antitumor ngokusebenzisa izindlela ezihlukahlukene, okuhlanganisa ukusebenza kwamasosha omzimba, ukuvinjelwa kwe-angiogenesis, kanye nemiphumela eqondile ye-antineoplastic. Kuye kwacwaningwa kabanzi ekwelapheni i-myeloma eminingi kanye ne-myelodysplastic syndrome kanye nokuphazamiseka kwe-lymphoproliferative okuhlanganisa i-lymphocytic leukemia engapheli (CLL) kanye ne-non-Hodgkin lymphoma. Ngokusho kocwaningo lwakamuva, i-Lnalidomide ikhuthaza futhi ibuyisele ukusebenza kwamasosha omzimba ezigulini ze-CLL ngokudala ukuvezwa ngokweqile kwama-molecule e-costimulatory kuma-leukemic lymphocytes ukubuyisela ukuzivikela kwe-humoral nokukhiqizwa kwama-immunoglobulins kanye nokwenza ngcono ikhono lama-T cell namaseli e-leukemic ukwakha ama-synapses ane-T. ama-lymphocyte.

Ireferensi

U-Ana Pilar Gonzalez-Rodriguez, u-Angel R. Payer, u-Andrea Acebes-Huerta, u-Leticia Hergo-Zapico, uMonica Villa-Alvarez, u-Esther Gonzalez-Garcia, no-Segundo Gonzalez. I-Lenalidomide kanye ne-lymphocytic leukemia engapheli. I-BioMed Research International 2013.

Ku-Vitro

I-Lenalidomide inamandla ekukhuthazeni ukwanda kwama-T cell kanye ne-IFN-γ kanye nokukhiqizwa kwe-IL-2. I-Lenalidomide ikhonjiswe ukuthi ivimbela ukukhiqizwa kwe-pro inflammatory cytokines TNF-α, IL-1, IL-6, IL-12 futhi iphakamise ukukhiqizwa kwe-cytokine elwa nokuvuvukala IL-10 kusuka kuma-PBMC abantu. I-Lenalidomide ilawula ukukhiqizwa kwe-IL-6 ngokuqondile futhi futhi ngokuvimbela amaseli amaningi e-myeloma (MM) kanye nokusebenzisana kwamaseli e-bone marrow stromal cell (BMSC), okwandisa i-apoptosis yamaseli e-myeloma[2]. Ukusebenzisana okuncike kumthamo yinkimbinkimbi ye-CRBN-DDB1 kubonwa nge-Thalidomide, iLenalidomide ne-Pomalidomide, ngamavelu e-IC50 angu-~30μM, ~3μM kanye ~3μM, ngokulandelana, Lawa maseli e-CRBN ancishisiwe (U266-CRBN60 kanye ne-U266-CRBN75) asabela kancane kunamaseli abazali emiphumeleni elwa nokwanda kweLenalidomide ebangeni lokuphendula umthamo elingu-0.01 kuye ku-10μM[3]. I-Lenalidomide, i-thalidomide analog, isebenza njengeglue yamangqamuzana phakathi kwe-E3 ubiquitin ligase cereblon yomuntu kanye ne-CKI.α kuboniswa ukuthi kubangele ukugcwala nokuwohloka kwalesi kinase, ngaleyo ndlela ngokunokwenzeka ukubulala amangqamuzana e-leukemic ngokusebenza kwe-p53.

Ubuthi bemithamo ye-Lenalidomide bufika ku-15, 22.5, kanye no-45 mg/kg nge-IV, IP, kanye nemizila ye-PO yokuphatha. Ikhawulelwe ukuncibilika emotweni yethu yokudosa i-PBS, le mithamo ephezulu efinyelelekayo ye-Lenalidomide ibekezelelwa kahle ngaphandle kokufa kwegundane elilodwa (kwesamba esithathiwe esine) kumthamo we-15 mg/kg IV. Ngokuphawulekayo, abukho obunye ubuthi obubonwa ocwaningweni kumithamo ye-IV ye-15 mg/kg (n=3) noma 10 mg/kg (n=45) noma kunoma iyiphi enye ileveli yomthamo ngemizila ye-IV, IP, kanye ne-PO.

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