Inkcazo

I-Lenalidomide (CC-5013) iphuma kwi-Thalidomide kunye ne-immunomodulator esebenzayo ngomlomo.I-Lenalidomide (CC-5013) i-ligand ye-ubiquitin E3 ligase cereblon (CRBN), kwaye ibangela ukukhethwa kwendawo yokuhlala kunye nokuthotywa kwezinto ezimbini ze-lymphoid transcription factor, i-IKZF1 kunye ne-IKZF3, nge-CRBN-CRL4 ubiquitin ligase.I-Lenalidomide (CC-5013) inqanda ngokukodwa ukukhula kwe-B-cell lymphomas evuthiweyo, kuquka i-myeloma eninzi, kwaye ibangela ukukhululwa kwe-IL-2 kwiiseli ze-T.

Imvelaphi

I-Lenalidomide (eyaziwa nangokuthi i-CC-5013), i-derivative yomlomo ye-thalidomide, i-antineoplastic agent ebonisa umsebenzi we-antitumor ngeendlela ezahlukeneyo, kubandakanywa nokusebenza kwe-immune system, i-angiogenesis inhibition, kunye nemiphumo echanekileyo ye-antineoplastic.Kuye kwafundwa ngokubanzi kunyango lwe-myeloma kunye ne-myelodysplastic syndrome kunye nokuphazamiseka kwe-lymphoproliferative kuquka i-lymphocytic leukemia engapheliyo (CLL) kunye ne-non-Hodgkin lymphoma.Ngokutsho kwezifundo zamva nje, i-Lnalidomide ikhuthaza kwaye ibuyisela ukusebenza kwamajoni omzimba kwizigulana ze-CLL ngokubangela ukugqithiswa kweemolekyuli ze-costimulatory kwi-lymphocytes ye-leukemic ukubuyisela ukhuseleko lwe-humoral kunye nokuveliswa kwe-immunoglobulins kunye nokuphucula amandla eeseli ze-T kunye neeseli ze-leukemic ukwenza i-synapses kunye ne-T. iilymphocytes.

Isalathiso

UAna Pilar Gonzalez-Rodriguez, u-Angel R. Umhlawuli, u-Andrea Acebes-Huerta, uLeticia Hergo-Zapico, uMonica Villa-Alvarez, u-Esther Gonzalez-Garcia, kunye noSegundo Gonzalez.I-Lenalidomide kunye ne-lymphocytic leukemia engapheliyo.I-BioMed Research International 2013.

I-In vitro

I-Lenalidomide inamandla ekukhuthazeni ukwanda kweeseli ze-T kunye ne-IFN-γ kunye nokuveliswa kwe-IL-2.I-Lenalidomide ibonakaliswe ukuba inqanda ukuveliswa kwe-pro inflammatory cytokines TNF-α, IL-1, IL-6, IL-12 kwaye iphakamise imveliso ye-anti-inflammatory cytokine IL-10 esuka kwi-PBMC yabantu.I-Lenalidomide ilawula ukuveliswa kwe-IL-6 ngokuthe ngqo kunye nangokunqanda iiseli ezininzi ze-myeloma (MM) kunye neeseli ze-stromal zethambo (BMSC), ezongeza i-apoptosis yeeseli ze-myeloma [2].Ukusebenzisana okuxhomekeke kwi-dose kunye ne-CRBN-DDB1 i-complex ibonwa kunye ne-Thalidomide, i-Lenalidomide kunye ne-Pomalidomide, kunye ne-IC50 ixabiso le-~30μM, ~3μM kunye ~3μM, ngokulandelanayo, Ezi zincitshisiweyo ze-CRBN iiseli zokubonisa (U266-CRBN60 kunye ne-U266-CRBN75) aziphenduli ngaphantsi kuneeseli zabazali kwimiphumo echasene ne-antiproliferative Lenalidomide kuluhlu lwe-dose-response ye-0.01 ukuya kwi-10μM[3].I-Lenalidomide, i-thalidomide analog, isebenza njengeglu yemolekyuli phakathi kwe-E3 ubiquitin ligase cereblon kunye ne-CKI.α kuboniswa ukubangela u-biquitination kunye nokuthotywa kwe-kinase, ngaloo ndlela ibulala iiseli ze-leukemic ngokusebenza kwe-p53.

Ubuthi bedosi yeLenalidomide ukuya kuthi ga kwi-15, 22.5, kunye ne-45 mg/kg nge-IV, IP, kunye neendlela ze-PO zolawulo.Ukunyinwa kukunyibilika kwisithuthi sethu sokudosa se-PBS, ezi dosi zeLenalidomide zifikelelekayo zinyamezeleka kakuhle ngaphandle kokufa kwempuku enye (yethamo ezine zizonke) kwidosi ye-15 mg/kg IV.Ngokucacileyo, akukho nanye i-toxicity ebonwayo kwisifundo kwi-IV imilinganiselo ye-15 mg / kg (n = 3) okanye i-10 mg / kg (n = 45) okanye nakweyiphi na enye inqanaba ledosi ngeendlela ze-IV, IP, kunye ne-PO.

Ugcino

Ubume beMichiza

Idatha yeBiological eNxulumeneyo

Idatha yeBiological eNxulumeneyo