Innovation in Clinical Trial Design and Product Promotion: Evolving the Patient Perspective With Regulatory and Technological Advances.

Clinical trials are evolving to innovative designs and capabilities. Clinical outcomes from pivotal trials are the backbone of good marketing practices. Novel study designs included in product labels and the uptick of innovative technology foreshadow a crescendo of patient empowerment not only in clinical trials, but also in the real-world setting.

Innovation in Clinical Trial Design and Product Promotion: Evolving the Patient Perspective With Regulatory and Technological Advances.

Clinical trials are evolving to innovative designs and capabilities. Clinical outcomes from pivotal trials are the backbone of good marketing practices. Novel study designs included in product labels and the uptick of innovative technology foreshadow a crescendo of patient empowerment not only in clinical trials, but also in the real-world setting.

Proteasome inhibitors stimulate both bone formation and hair growth by similar mechanisms.

We propose that the remodeling process that occurs in localized areas on endosteal bone surfaces and in Haversian canals shares many features in common with the mammalian hair cycle. In both, there are phases of resorption or regeneration, a transition phase, and then a phase of growth, termed anagen in the hair follicle, and formation in the bone remodeling cycle. Furthermore, we suggest that these processes both use the same molecular mechanisms, and specifically the Hedgehog-BMP-Wnt signal transduction cascades.

Selective inhibitors of the osteoblast proteasome stimulate bone formation in vivo and in vitro.

We have found that the ubiquitin-proteasome pathway exerts exquisite control of osteoblast differentiation and bone formation in vitro and in vivo in rodents. Structurally different inhibitors that bind to specific catalytic beta subunits of the 20S proteasome stimulated bone formation in bone organ cultures in concentrations as low as 10 nM. When administered systemically to mice, the proteasome inhibitors epoxomicin and proteasome inhibitor-1 increased bone volume and bone formation rates over 70% after only 5 days of treatment.

Guanosine nucleotides inhibit different syndromes of PTHrP excess caused by human cancers in vivo.

There are two well-described syndromes caused by tumor production of parathyroid hormone-related peptide (PTHrP), namely osteolytic bone disease associated with breast cancer and humoral hypercalcemia of malignancy (HHM) that occurs with or without bone metastasis. Both syndromes have been shown experimentally to be inhibited by neutralizing antibodies to PTHrP. In a search for small-molecule inhibitors of PTHrP production or effects, we have identified guanine-nucleotide analogs as compounds that inhibit PTHrP expression by human tumor cells associated with these syndromes.