Notch regulation of early thymocyte development.

Notch signaling plays multiple roles in T cell development. Following thymic entry, Notch signals are required to specify the T cell fate from a multipotent hematopoietic progenitor. At subsequent steps in early T cell development, Notch provides important differentiation, survival, proliferation and metabolic signals.

Suppression of BRAF(V599E) in human melanoma abrogates transformation.

Activating mutations in the BRAF serine/threonine kinase are found in >70% of human melanomas, of which >90% are BRAF(V599E). We sought to investigate the role of the BRAF(V599E) allele in malignant melanoma. We here report that suppression of BRAF(V599E) expression by RNA interference in cultured human melanoma cells inhibits the mitogen-activated protein kinase cascade, causes growth arrest, and promotes apoptosis.

Long-term medical care of testicular cancer survivors.

Testicular cancer is the most common solid tumor diagnosed in men 20 to 35 years of age. Because of highly effective treatments that may include surgery, chemotherapy, and radiation therapy, most patients become long-term survivors. Health-related issues that confront testicular cancer survivors include the late medical effects of chemotherapy, the late relapse of disease, the development of second cancers, the effect of the disease and treatment on fertility, and the psychosocial consequences.

The promise of T-lymphocyte immunotherapy for the treatment of malignant disease.

Exciting developments in basic immunology and tumor biology have increased our understanding of mechanisms of interactions between tumor cells and the immune system. The rapid translation of bench research to clinical applications has led to immense progress in the field of cellular immunotherapy. The rationale for the use of T cells for adoptive transfer is that tumors are immunogenic and that the transferred cells have the capacity to recognize tumor cells and elicit an immune response that leads to specific tumor cell killing.

Antigen specific T lymphocyte activation.

Following recognition of foreign antigens, the T cell antigen receptor (TCR) transduces signals leading to clonal expansion and differentiation into effector cells. Engagement of the TCR results first in the activation of cytosolic protein tyrosine kinases, followed by initiation of multiple signaling cascades. Recently, it has been shown that regulation and integration of these signaling pathways requires formation of multimolecular complexes and the recruitment of these complexes to specific regions within the cell.