The anti-tumor agent sagopilone shows antiresorptive effects both in vitro and in vivo.

UNLABELLED: Sagopilone, a fully synthetic epothilone and very potent anti-tumor agent, has proved to be efficient in inhibiting bone destruction and tumor burden in a mouse model of breast cancer bone metastasis. In addition to its antiproliferative effects, this study shows direct effects of sagopilone on bone resorption and osteoclast activity. INTRODUCTION: Sagopilone, a novel fully synthetic third-generation epothilone, has proved to be efficient in inhibiting bone destruction and tumor burden in a mouse model of breast cancer bone metastasis. The aim of this study was to investigate whether the effect was primarily due to sagopilone's antiproliferative effect and consequent inhibition of tumor cell growth, or if sagopilone exerts direct effects on bone resorption and osteoclast activity. METHODS: Sagopilone was studied and compared to paclitaxel in vitro in human osteoclast differentiation and activity cultures. For studying the potential of sagopilone for inhibiting bone resorption in vivo, a mouse model of ovariectomy (ovx)-induced osteoporosis was utilized. RESULTS: Sagopilone inhibited osteoclast differentiation and activity more efficiently than paclitaxel and showed less cytotoxicity. Whereas sagopilone showed inhibitory effects on human osteoclast differentiation and activity already at 5 and 15 nM, respectively, paclitaxel started to show effects only at 20 and 100 nM concentrations, respectively. Sagopilone treatment increased BMD In the mouse ovx model even though a non-optimized dose was used which is effective in tumor-bearing mice. CONCLUSION: This is the first study to evaluate sagopilone's effects on bone resorption in non-cancerous situation. The evidence that sagopilone is beneficial for bone will strengthen the status of sagopilone as an anti-cancer compound compared to other microtubule stabilizing agents.

[Frontal syndrome of progressive supranuclear palsy]. / Le syndrome frontal de la paralysie supranucléaire progressive.

Neuropsychological findings in 10 clinical cases of progressive supranuclear palsy are presented. Patients were aged 52 to 80 and the duration of their illness was 1 to 5 years. Severe psychological disturbances e.g. depression or outbursts of irritability were prominent features in 5 patients. Formal neuropsychological testing disclosed mental slowing, impaired attention, reduced verbal fluency and elaborated linguistic abilities, poor abstract thinking and reasoning, mild to moderate memory loss, dynamic apraxia, grasping, motor impersistence, imitation and utilization behaviour. The clinical similarities between these neuropsychological changes and frontal lobe syndromes, together with the lack of cortical involvement, suggest that the "dementia" of progressive supranuclear palsy could be explained by deactivation of the frontal cortex by subcortical lesions. The special importance of pallidal and mesencephalic reticular involvement in the syndrome is hypothetized.

[Echolalic repetition and severe comprehension disorders. Left hemisphere deactivation syndrome? (author's transl)]. / Répétition écholalique et troubles sévères de la compréhension. Syndrome de dé-activation de l'hémisphère gauche?

An aphasic patient presented with suppression of spontaneous speech, correct repetition, and disturbed comprehension and denomination. The association of a lesion on CT scanning affecting the deep regions of the left hemisphere, and extinction of the right ear to dichotic audition, leads to a discussion of the role of the right hemisphere in remaining psycholinguistic capabilities.