Abstract:
:After the initial dramatic effects, observed in a Lewis lung carcinoma animal model, using a combination of thymosin alpha 1 (Talpha1) and interferon (IFN) after cyclophosphamide, a number of other preclinical models in mice (Friend erythroleukemia and B16 melanoma) and in rats (DHD/K12 colorectal cancer liver metastasis) have confirmed the efficacy of the combination therapy with Talpha1 and either IFN or IL-2 plus chemotherapy. These results provided the scientific foundation for the first clinical trials using Talpha1 in combination with BRMs and/or chemotherapy. Pivotal trials in advanced non-small cell lung cancer (NSCLC) and melanoma with Talpha1 and IFN-alpha low doses after cis-platinum or dacarbazine produced the first evidence of the high potentiality of this approach in the treatment of human cancer. The combination of Talpha1 and IFN-alpha was also used in patients affected by chronic B and C hepatitis including IFN-nonresponders and infected by precore mutants or genotype 1b. Further studies demonstrated additional biological activities clarifying the mechanism of action of Talpha1, partially explaining the synergism with IFN. It has been shown the capacity of activating infected dendritic cells through Toll-like receptor signaling, thus influencing the inflammation balance, and of increasing the expression of tumor, viral, and major histocompatibility complex (MHC) I antigens. Dose-response studies suggested the possibility of improving the efficacy of this molecule reducing the overall toxic. Based on these information two clinical trials are ongoing: a large phase II on advanced melanoma patients treated with Talpha1 at different doses after dacarbazine and a phase III one, on IFN-resistant hepatitis C virus (HCV) patients treated with a triple combination (IFN, ribavirin, and Talpha1).
journal_name
Ann N Y Acad Scijournal_title
Annals of the New York Academy of Sciencesauthors
Garaci E,Favalli C,Pica F,Sinibaldi Vallebona P,Palamara AT,Matteucci C,Pierimarchi P,Serafino A,Mastino A,Bistoni F,Romani L,Rasi Gdoi
10.1196/annals.1415.044subject
Has Abstractpub_date
2007-09-01 00:00:00pages
225-34eissn
0077-8923issn
1749-6632pii
annals.1415.044journal_volume
1112pub_type
杂志文章abstract::Enhancer DNA decoy oligonucleotides (ODNs) inhibit transcription by competing for transcription factors. A decoy ODN composed of the cAMP response element (CRE) inhibits CRE-directed gene transcription and tumor growth without affecting normal cell growth. We used DNA microarrays to analyze the global gene expression ...
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abstract::The results reviewed here demonstrate that vestibulospinal and vestibulo-ocular interneurons in the chicken embryo are organized into coherent clusters, each of which occupies a unique spatial domain and has a characteristic axon trajectory. Moreover, the vestibulo-ocular clusters have specific termination patterns in...
journal_title:Annals of the New York Academy of Sciences
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abstract::Entomopathogenic fungi are promising alternatives to chemical acaricides in controlling tick populations; however, biological formulations are required to improve conidial performance of these pathogens in the field. This study evaluated the effect of in vitro treatment of Rhipicephalus sanguineus with conidial formul...
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journal_title:Annals of the New York Academy of Sciences
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journal_title:Annals of the New York Academy of Sciences
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journal_title:Annals of the New York Academy of Sciences
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