Differential 24 h responsiveness of Prox1-expressing precursor cells in adult hippocampal neurogenesis to physical activity, environmental enrichment, and kainic acid-induced seizures.

Regulation of adult hippocampal neurogenesis in mice responds to behavioral stimuli, including physical activity (RUN) and the exposure to enriched environments (ENR). If studied after days or weeks, these stimuli and the pathological stimulus of kainic acid-induced seizures (KA) show differential effects on different developmental stages of adult neurogenesis. The question thus arose, whether such differential effects would also be apparent under very acute conditions. To further refine our method for identifying key restriction points in adult neurogenesis we here used the first expression of granule cell-specific transcription factor prospero-related homeobox 1 (Prox1) to identify lineage-determined progenitor cells in a nestin-green fluorescent protein (GFP) reporter gene mouse and labeled proliferating precursor cells with bromodeoxyuridine (BrdU). Twenty-four hours after the stimulus adult neurogenesis showed a very similar response to the three paradigms, in that cell proliferation increased. Detailed analysis, however, revealed the following new results: (1) KA, but not RUN and ENR stimulated the division of radial glia-like type-1 cells, (2) KA led to the disappearance of proliferative undetermined progenitor cells (type-2a), (3) only RUN increased proliferation of type-2a cells, (4) ENR and KA, in contrast, acted on lineage-determined progenitor cells (type-2b and type-3) even under acute conditions, and (5) only in the case of KA the short-term stimulus resulted in measurably increased survival of newborn neurons 4 weeks later. These results confirm and specify the idea that in the course of neuronal development in the adult hippocampus, precursor cells acutely sense and distinguish various forms of "activity" differentially and translate these stimuli into defined responses based on their stage of development.

[O-Twist Marker for marking breast cancer under neoadjuvant chemotherapy--first results]. / Einsatz des O-Twist-Markers zur Lokalisation von Mammakarzinomen unter neoadjuvanter Chemotherapie--erste Ergebnisse.

PURPOSE: Evaluation of ultrasound-guided percutaneous marking of breast cancer using an "O-Twist Marker" (BARD GmbH, Karlsruhe, Germany) in patients undergoing neoadjuvant chemotherapy. In the event of complete remission, the lesion of interest can be missed after completion of therapy. In these cases marking of the tumor site is essential. MATERIALS AND METHODS: We monitored patients with breast cancer proven by biopsy who were undergoing neoadjuvant chemotherapy with ultrasound. In cases in which the follow-up ultrasound examination after the second chemotherapy cycle showed a significant tumor mass reduction (> 30 %), we pinpointed the lesion with an ultrasound-guided "O-Twist Marker". The position of the marker was documented by ultrasound and mammography. Between January and November 2006, we marked 7 patients. RESULTS: The visibility of the marker was excellent on mammography, but only moderate on ultrasound. The marker did not cause any imaging interference. The instrument was easy to operate. We did not detect any migration of the marker. In 3/7 patients it would have been possible to locate the remaining tumor tissue after the completion of neoadjuvant chemotherapy without the marking. In 4/7 cases the clip was very useful or even essential for preoperative site determination. CONCLUSION: The use of "O-Twist Marker" is a reliable and effective technique for locating breast cancer sites in remission during neoadjuvant chemotherapy. The visibility of the marker on ultrasound should be improved. In 57 % of the cases tumor marking was advantageous for surgical procedures.

Long-term stabilization in patients with malignant glioma after treatment with liposomal doxorubicin.

BACKGROUND: Resistance to chemotherapeutic agents and poor blood-brain barrier penetration are major limitations in the treatment of malignant glioma. To improve drug delivery across the blood-brain barrier, the authors used doxorubicin as liposomal encapsulated formulation (Caelyx, Scheringh-Plough, Munich, Germany) in therapy of recurrent malignant glioma. METHODS: Fifteen patients with recurrent high-grade gliomas were included in the study. Of these, 13 patients could be evaluated, including 6 patients with glioblastoma, 1 patient with gliosarcoma and 6 patients with anaplastic astrocytoma. The treatment consisted of liposomal doxorubicin (20 mg/m(2)), applied intravenously every 2 weeks. RESULTS: Stabilization of the disease was observed in 54% (7 of 13) of patients. Partial response and complete response (CR) were not observed. Median time-to-progression was 11 weeks. Progression free survival at 12 months was 15%. Median overall survival (OS) after doxorubicin therapy was 40.0 weeks, whereas the median OS after diagnosis reached 20.0 months (87.0 weeks). Doxorubicin was well tolerated, with main side effects being palmoplantar erythrodysesthesia occurring in 38% and myelotoxicity (World Health Organization Grade 3-4) in 31% of the patients. CONCLUSIONS: Doxorubicin has been shown to be a safe treatment with moderate activity that may lead to long-term stabilization in recurrent high-grade glioma patients. Of note, median OS after all and after initiation of recurrence therapy was prolonged in comparison with the OS in other Phase II studies, as recently described by Wong et al. (Wong ET, Hess KR, Gleason MJ, Jaeckle KA, Kyritsis AP, Prados MD, et al. Outcomes and prognostic factors in recurrent glioma patients enrolled onto phase II clinical trials. J Clin Oncol 1999;17:2572.).