Canonical Wnt signaling has been implicated in the regulation of multiple myeloma (MM) growth. Here, we investigated whether the targeting of this pathway with a novel pharmacological inhibitor ICG-001 would result in an anti-tumor effect and improvement of chemosensitivity in MM. As expected, ICG-001 specifically down-regulated β-catenin/TCF-mediated transcription in MM cells. Treatment with ICG-001 resulted in growth arrest and apoptosis in MM cell lines and primary MM cells. Moreover, ICG-001 enhanced the cytotoxic effects of doxorubicin and melphalan and abrogated chemoresistance of MM cells to these chemotherapeutics induced by bone marrow stroma. The cytotoxic effect of ICG-001 was caspase-dependent and mediated through transcriptional up-regulation of BH3-only pro-apoptotic members of the Bcl-2 family Noxa and Puma but not through inhibition of canonical Wnt signaling. ICG-001 selectively induced apoptosis in primary MM cells but did not affect non-MM cells of the bone marrow microenvironment. Experiments using a xenograft model of MM showed substantial anti-tumor effects of this compound in vivo. Thus, our study demonstrated that the small molecule inhibitor ICG-001 has strong anti-MM effects and could be developed further for therapeutic intervention in this disease.

Patient care is of the utmost importance in the hospital setting. Bedrest and immobility during hospitalization, especially in the surgical and intensive care setting, place the patient at high risk for pressure ulcers. It is very important to prevent or notice a pressure ulcer forming due to the significant health care costs involved and patient health associated with them. Various measures are in place to prevent patients from getting pressure ulcers, but a newer material, silicone foam dressings, has been introduced as an alternative solution for the prevention of these ulcers. We review the current literature to examine whether the standard protocol or silicone material is superior to the prevention of pressure ulcer formation. We conclude that silicone foam dressings, when used as prophylactic treatment, seems very promising and may even be superior to the standard care of prevention. However, there were limitations to some studies and further research is needed to confirm the role of silicone foam dressings.

Multiple myeloma (MM), a blood cancer characterized by the uncontrolled proliferation of plasma cells, remains incurable by current therapy. Notch signaling has been implicated in the growth and chemoresistance of various cancer types including MM, and therefore we hypothesized that targeting the Notch pathway could be beneficial for the treatment of this disease. Here, we report an anti-tumor effect of Notch/g-secretase inhibitor RO4929097 in a pre-clinical model of MM. We demonstrate that this effect was associated with decreased angiogenesis and significant down-regulation of TGF-b1. In addition, we also show that treatment with RO4929097 results in decreased number and functional activity of osteoclasts. Taken together, our data indicate that targeting Notch may be considered as a new strategy to be tested for MM therapy.