Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:6.2.1.7 (BAL)
 1,977 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

BRIIL-2 is a clinical study for evaluation of efficacy and toxicity of third line treatment of pulmonary metastasis from renal cancer and melanoma with flexible bronchoscopic istillation of IL-2. Moreover, we evaluate local (BALT) and peripheral lymphocytic activation during this IL-2 administration. Up today we enrolled two patients with pulmonary metastasis from renal cancer already treated with two lines of molecular therapy, chemotherapy or systemic immunotherapy. Regarding to immunologic stimulation, lymphocytic fraction decreased from 21 to 2% in the first and from 10.5 to 6% in the second patient, indicating lymphocytic enrollment for activation, while TCD4/CD8 ratio is stable. In both patients we also observed a significant increase of HLA-DR in T lymphocytes (CD3) either in BAL or in peripheral blood. No significant major toxicities were observed after broncho-istillation, even if the dose was progressively increased. Thus IL-2 broncho-istillation could represent a valid administration modality to obtain an effective immunologic stimulation either local or systemic.
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PMID:[IL-2 bronchoscopic istillation and immune cell activation: preliminary results of the BRIIL-2 study for treatment of pulmonary metastasis from renal cancer and melanoma]. 1945 4

Deltex-3-like (DTX3L), an E3 ligase, is a member of the Deltex (DTX) family and is also called B-lymphoma and BAL-associated protein (BBAP). Previously, we established RFP/RET-transgenic mice, in which systemic hyperpigmented skin, benign melanocytic tumor(s) and melanoma(s) develop stepwise. Here we showed that levels of Dtx3l/DTX3L in spontaneous melanoma in RFP/RET-transgenic mice and human melanoma cell lines were significantly higher than those in benign melanocytic cells and primarily cultured normal human epithelial melanocytes, respectively. Immunohistochemical analysis of human tissues showed that more than 80% of the melanomas highly expressed DTX3L. Activity of FAK/PI3K/AKT signaling, but not that of MEK/ERK signaling, was decreased in Dtx3l/DTX3L-depleted murine and human melanoma cells. In summary, we demonstrated not only increased DTX3L level in melanoma cells but also DTX3L-mediated regulation of invasion and metastasis in melanoma through FAK/PI3K/AKT but not MEK/ERK signaling. Our analysis in human BRAFV600E inhibitor-resistant melanoma cells showed about 80% decreased invasion in the DTX3L-depleted cells compared to that in the DTX3L-intact cells. Thus, DTX3L is clinically a potential therapeutic target as well as a potential biomarker for melanoma.
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PMID:Deltex-3-like (DTX3L) stimulates metastasis of melanoma through FAK/PI3K/AKT but not MEK/ERK pathway. 2603 50