Neil Sidell

Retinoic acid (RA) induced concentration-dependent morphologic differentiation and growth inhibition in the LA-N-1 human neuroblastoma cell line. Time course studies demonstrated a significant increase in the formation of long neurites in LA-N-1 cultures within 48 hours of RA addition; maximum expression of differentiation occurred at approximately 4 days. This differentiation profile corresponded to a detectable decrease in [3H]thymidine incorporation at 48 hours and complete inhibition of cell growth after 3-4 days. The RA-induced morphologic differentiation and growth inhibition persisted despite removal of the drug. A soft agar assay system showed that RA also inhibited the ability of LA-N-1 cells to form anchorage-independent colonies and induced morphologic differentiation in colonies that did develop. These findings suggest that RA promoted the differentiation of LA-N-1 neuroblastoma cells, resulting in an altered expression of the malignant phenotype.

Antibodies sustain viral control For many infected individuals, antiretroviral therapy (ART) means that an HIV-1 diagnosis is no longer a death sentence. But the virus persists in treated individuals, and complying with the intense drug regimen to keep virus loads down can be challenging for patients. Seeking an alternative, Byrareddy et al. treated ART-suppressed monkeys with antibodies targeting α4β7 integrin. When ART was halted in the antibody-treated animals, viral loads stayed undetectable, and normal CD4 T cell counts were maintained for over 9 months—and persisted—even after stopping the antibody therapy. Science , this issue p. 197

Neuroblastoma is a childhood solid tumor composed of primitive cells derived from precursors of the autonomic nervous system. This neoplasm has the highest rate of spontaneous regression of all cancer types and has been noted to undergo spontaneous and chemically induced differentiation into elements resembling mature nervous tissue. As such, neuroblastoma has been a prime model system for the study of neuronal differentiation and the process of cancer cell maturation. In this paper we review those agents that have been described to induce the differentiation of neuroblastoma, with an emphasis on the effects and possible mechanisms of action of a group of related compounds, the retinoids. With this model system and the availability of subclones that are both responsive and resistant to chemically induced differentiation, fundamental questions regarding the mechanisms and processes underlying cell maturation have become more amenable to in vitro study.