Our results could facilitate the practice of personalized cancer medicine based on the gene expression profile of the patients. (C) 2014 Elsevier Inc. All rights reserved.”
“Bisphosphonates (BPs) are in clinical use for the treatment of breast cancer patients with bone metastases. Their anti-resorptive effect is mainly explained by inhibition of osteoclast

activity, but recent evidence also points to a direct action of BPs on bone-forming osteoblasts. However, the mechanisms how BPs influence osteoblasts BMS-777607 in vitro and their interactions with breast cancer cells are still poorly characterized. Human osteoblasts isolated from bone specimens were characterized in depth by their expression of osteogenic marker Copanlisib in vivo genes. The influence of the nitrogen-containing BPs zoledronate (Zol), ibandronate (Iban), and pamidronate (Pam) on molecular and cellular functions of osteoblasts was assessed focusing on cell proliferation and viability, apoptosis, cytokine secretion, and osteogenic-associated genes. Furthermore, effects of BPs on osteoblast-breast tumor cell interactions were examined in an established in vitro model system. The BPs Zol and Pam inhibited cell viability of osteoblasts. This effect was mediated by an induction of caspase-dependent apoptosis in osteoblasts. By interfering with the mevalonate pathway, Zol also reduces the proliferation of osteoblasts.

The expression of phenotypic markers of osteogenic differentiation was altered by Zol and Pam. In addition, both BPs strongly influenced the secretion of the chemokine CCL2 by osteoblasts. Breast cancer cells also responded to Zol and Pam with a reduced cell adhesion to osteoblast-derived extracellular matrix molecules and with a decreased migration in response to osteoblast-secreted factors.

BPs revealed Microtubule Associat inhibitor prominent effects on human osteoblasts. Zol and Pam as the most potent BPs affected not only the expression of osteogenic markers, osteoblast viability, and proliferation but also important osteoblast-tumor cell interactions. Changing the osteoblast metabolism by BPs modulates migration and adhesion of breast cancer cells as well.”
“Objective We examine data from short-term placebo-controlled and comparator-controlled clinical trials of ziprasidone in schizophrenia to confirm the predictive capacity of early symptom changes for response. We pose the question of how early is too early to consider “stay or switch” and evaluate the predictive capability of a clinical measure in this regard.\n\nMethods We presented two separate pooled analyses of (i) two placebo-controlled and (ii) two active comparator (risperidone and olanzapine) randomized trials of ziprasidone in schizophrenia. Relationship between early changes in Positive and Negative Syndrome Scale (PANSS) total, Brief Psychiatric Rating Scale (BPRS), and Clinical Global Impression-Improvement (CGI-I) scores and treatment outcome was evaluated.