Role of cytokine therapy for renal cell carcinoma in the era of targeted agents.

Starting in the late 1980s, cytokines were considered the mainstay of treatment for locally advanced or metastatic renal cell carcinoma (rcc) because of a lack of improved survival with either chemotherapy or hormonal therapy alone. The cytokine agents interferon alfa (IFNalpha) and interleukin-2 (IL-2) have been the most evaluated, but a low overall response rate and a marginal survival advantage, coupled with significant toxicity, make these therapies less than ideal. Although complete tumour responses have occasionally been seen with high-dose il-2, this therapy is associated with significant morbidity and mortality, and its approval has been based on limited nonrandomized evidence. Newer anti-angiogenesis agents have been evaluated as single agents and in combination with INFalpha, and these are now considered the standard of care for most patients with rcc. However, cytokines may still occasionally be recommended when angiogenesis inhibitors are not available or are contraindicated. In the present paper, we discuss the evidence for the use of cytokine therapy in the setting of pre- and post-targeted therapy for RCC.

Continuous phencyclidine treatment induces schizophrenia-like hyperreactivity of striatal dopamine release.

Functional dopaminergic hyperactivity is a key feature of schizophrenia. Recent in vivo imaging studies have demonstrated greater striatal dopamine release in response to amphetamine challenge in schizophrenia subjects than in normal controls. N-methyl-D-aspartate (NMDA) receptors are known to play a prominent role in regulation of striatal dopamine release. In humans, NMDA antagonists induce a psychotic state that closely resembles schizophrenia. The present study investigates the degree to which chronic continuous administration of the NMDA antagonist phencyclidine (PCP) induces schizophrenia-like hyperreactivity of striatal dopamine release to amphetamine in rodents. Rats were treated with 10 or 15 mg/kg/d PCP for two weeks by osmotic minipump, and striatal dopamine release to amphetamine challenge (1 mg/kg) was monitored by microdialysis. PCP-treated rats showed significant enhancement in amphetamine-induced dopamine release, along with significantly enhanced locomotor activity. These findings support the concept that NMDA receptor dysfunction may contribute to dopaminergic dysfunction in schizophrenia.