Bisphosphonates antagonise bone growth factors' effects on human breast cancer cells survival

Bone tissue constitutes a fertile 'soil' for metastatic tumours, notably breast cancer. High concentrations of growth factors in bone matrix favour cancer cell proliferation and survival, and a vicious cycle settles between bone matrix, osteoclasts and cancer cells. Classically, bisphosphonates interrupt this vicious cycle by inhibiting osteoclast-mediated bone resorption. We and others recently reported that bisphosphonates can also induce human breast cancer cell death in vitro, which could contribute to their beneficial clinical effects. We hypothesised that bisphosphonates could inhibit the favourable effects of 'bone-derived' growth factors, and indeed found that bisphosphonates reduced or abolished the stimulatory effects of growth factors (IGFs, FGF-2) on MCF-7 and T47D cell proliferation and inhibited their protective effects on apoptotic cell death in vitro under serum-free conditions. This could happen through an interaction with growth factors' intracellular phosphorylation transduction pathways, such as ERK1/2-MAPK. In conclusion, we report that bisphosphonates antagonised the stimulatory effects of growth factors on human breast cancer cell survival and reduced their protective effects against apoptotic cell death. Bisphosphonates and growth factors thus appear to be concurrent compounds for tumour cell growth and survival in bone tissue. This could represent a new mechanism of action of bisphosphonates in their protective effects against breast cancer-induced osteolysis.Journal ArticleResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe

Impact of internet of things (IoT) in disaster management: a task-technology fit perspective

YesDisaster management aims to mitigate the potential damage from the disasters, ensure immediate and suitable assistance to the victims, and attain effective and rapid recovery. These objectives require a planned and effective rescue operation post such disasters. Different types of information about the impact of the disaster are, hence, required for planning an effective and immediate relief operation. The IoT technology available today is quite mature and has the potential to be very useful in disaster situations. This paper analyzes the requirements for planning rescue operation for such natural disasters and proposes an IoT based solution to cater the identified requirements. The proposed solution is further validated using the task-technology fit (TTF) approach for analyzing the significance of the adoption of IoT technology for disaster management. Results from the exploratory study established the core dimensions of the task requirements and the TTF constructs. Results from the confirmatory factor analysis using PLS path modelling, further, suggest that both task requirements and IoT technology have significant impact on the IoT TTF in the disaster management scenario. This paper makes significant contributions in the development of appropriate constructs for modeling TTF for IoT Technology in the context of disaster management

The pharmacology of bisphosphonates and new insights into their mechanisms of action.

Bisphosphonates are chemically stable analogs of inorganic pyrophosphate, which are resistant to breakdown by enzymatic hydrolysis. The biological effects of bisphosphonates on calcium metabolism were originally ascribed to their physico-chemical effects on hydroxyapatite crystals. Although such effects may contribute to their overall action, their effects on cells are probably of greater importance, particularly for the more potent compounds. Remarkable progress has been made in increasing the potency of bisphosphonates as inhibitors of bone resorption, and the most potent compounds in current use are characterized by the presence of a nitrogen atom at critical positions in the side chain which, together with the bisphosphonate moiety itself, seems to be essential for maximal activity. As a class the bisphosphonates offer a very effective means of treating Paget's disease