1,721,025 research outputs found
Updating on tumor markers in tissues and biological fluids: Immunology of host-tumor interaction.
No full textThe ErbB2 receptor in gastric cancer. the quick-change artist
Full text linkThe ErbB family of receptors is providing the oncogenic signals necessary to cells to become transformed. In gastric cancer (GC) the ErbB2 (HER2) expression is associated with a poor prognosis, but addition of ErbB-targeted therapeutics to chemotherapy has produced unsatisfactory results with moderate improved outcomes for patients. The ToGA trail has revolutionized the treatment of GC, introducing the use of trastuzumab and changing the poor prognosis of these patients. However, this study reported only a modest prolongation of progression-free survival (PFS) and overall survival (OS) in patients with high expression of ErbB2 protein, with a large percentage of initially good responders, then becoming refractory to therapy within one year. These findings indicate the occurrence of resistant phenotypes
arising from diverse adaptive and genetic changes. Due to the promiscuity of ErbB2 in the EGFR family signaling network, the use of ErbB targeted mono-therapies certainly contributes to a redistribution of the stoichiometry among receptors leading to the activation of compensatory pathways, suggesting that survival of cancer cells is sustained, at least in part, by the network of the ErbB receptors and their ligands. For these reasons, the use of combination therapies is becoming the most logical strategy for any type of cancer treatment, including GC. In this review we summarize information regarding mechanisms, pathways and molecules involved in the resistance to ErbB-targeted molecules with the intent to provide rational guidelines for developing more efficient therapeutic approaches
Molecole chimeriche con recettori innati di attivazione per immunoterapia
No full textGli Fc-CR sono progettati per reindirizzare le funzioni delle cellule T contro cellule target opsonizzate. Ciò è consentito dalla presenza di un modulo FcR extracellulare del recettore chimerico in grado di legare gli anticorpi monoclonali e di elementi trasduzionali di signaling (CD28/-chain) nella sua porzione interna. Gli "c-CR implementano l’attività del sistema immunitario aggiungendo una risposta T dipendente per attivazione anticorpale (ADCC-like), mantenendo gli effetti clinicamente rilevanti degli anticorpi terapeutici disponibili per il trattamento dei tumori, e che possono essere diversamente somministrati ai pazienti durante la terapia.
Gli Fc-CR codificano per proteine chimeriche transmembrana dotata di duplice funzione:
a) complessano il frammento Fc delle IgG tramite la porzione extracellulare del frammento FcRI del CD64 (CD64-CR); o del FcRIIb del CD32 (CD32-CR).
b) Attivano il macchinario litico in cellule effettrici del sistema immunitario tramite le porzioni intracellulari del CD28 e della -chain presenti nel Fc-CR.
Il meccanismo di azione prevede la formazione di un ponte fra la “cellula bersaglio” e il “Linfocita T riprogrammato” mediato da anticorpi monoclonali che riconoscano antigeni presenti sulla cellula target.
Gli Fc-CR sono recettori chimerici "Universali" specificamente progettati per ampliare le opzioni immunoterapeutiche legate all’utilizzo di anticorpi e per superare fenomeni di resistenza legati alla selezione di cellule tumorali antigene negative. I linfociti T trasdotti con Fc-CR migliorano l'efficacia terapeutica degli anticorpi normalmente utilizzati nelle terapie oncologiche
WW domain containing E3 ubiquitin protein ligase 1 targets the full-length ErbB4 for ubiquitin-mediated degradation in breast cancer
No full textErbB4, a member of the epidermal growth factor receptor family, plays a role in normal breast and breast cancer development by regulating mammary epithelial cell proliferation, survival and differentiation. In this study, we show that WWP1, a C2-WW-HECT type E3 ubiquitin ligase, binds, ubiquitinates and destructs ErbB4-CYT1, but much less efficiently for CYT2, isoforms (both JMa and JMb). The protein-protein interaction occurs primarily between the first and third WW domains of WWP1 and the second PY motif of ErbB4. Knockdown of WWP1 by two different small interfering RNAs increases the endogenous ErbB4 protein levels in both MCF7 and T47D breast cancer cell lines. In addition, overexpression of the wild type, but not the catalytic inactive WWP1, dramatically decreases the endogenous ErbB4 protein levels in MCF7. Importantly, we found that WWP1 negatively regulates the heregulin-beta 1-stimulated ErbB4 activity as measured by the serum response element report assay and the BRCA1 mRNA expression. After a systematic screening of all WWP1 family members by small interfering RNA, we found that AIP4/Itch and HECW1/NEDL1 also negatively regulate the ErbB4 protein expression in T47D. Interestingly, the protein expression levels of both WWP1 and ErbB4 are higher in estrogen receptor-alpha-positive than in estrogen receptor-alpha-negative breast cancer cell lines. These data suggest that WWP1 and its family members suppress the ErbB4 expression and function in breast cancer. Oncogene (2009) 28, 2948-2958; doi:10.1038/onc.2009.162; published online 29 June 200
Oncogeni e fattori di crescita. In: "Il Cancro": ricerca ed applicazioni cliniche
No full textLe Scienz
Analysis of the possibile transport to the nucleus of the KGFR and its ligands at late steps of endocytosis.
No full text
Mitogenic signal trasduction by erbB-3: evidence for constitutive activation in human mammary carcinomas.
No full textBIOTHECNOLOGY TODA
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