Palifermin for patients with haematological malignancies: shifting nursing practice from symptom relief to prevention of oral mucositis.

Oral mucositis (OM) is an extremely debilitating side effect of certain high-dose chemotherapy and radiotherapy regimens. It is especially prevalent in patients with haematological malignancies who undergo myeloablative therapy and autologous haematopoietic stem cell transplantation (HSCT). Severe erosion of the lining of the oral cavity can make patients' everyday activities, including eating, drinking, swallowing, and talking, difficult or even impossible. Palifermin (Kepivance) was approved in Europe in 2005 for both prevention and treatment of this painful condition. It works at the epithelial level to help protect cells in the mouth and throat from the damage caused by chemotherapy and radiation, and to stimulate growth and development of new epithelial cells to build up the mucosal barrier. In the pivotal clinical trial, palifermin reduced the incidence, severity, and duration of severe OM. Palifermin was also well-tolerated; common adverse reactions reported included rash, pruritus, erythema, edema, pain, fever, arthralgia, mouth or tongue disorders, and taste alteration. In this article, nurses who are skilled in caring for patients undergoing HSCT review their clinical experience with palifermin, sharing practical advice about its reconstitution, dosing, and administration. By familiarising themselves with the use of palifermin, nurses can influence a shift in clinical practice away from OM symptom management to the more satisfactory situation of protecting patients against severe OM.

Hsp90 inhibition accelerates cell lysis. Anti-Hsp90 ribozyme reveals a complex mechanism of Hsp90 inhibitors involving both superoxide- and Hsp90-dependent events.

The 90 kDa heat shock protein, Hsp90, is an abundant molecular chaperone participating in the cytoprotection of eukaryotic cells. Here we analyzed the involvement of Hsp90 in the maintenance of cellular integrity using partial cell lysis as a measure. Inhibition of Hsp90 by geldanamycin, radicicol, cisplatin, and novobiocin induced a significant acceleration of detergent- and hypotonic shock-induced cell lysis. The concentration and time dependence of cell lysis acceleration was in agreement with the Hsp90 inhibition characteristics of the N-terminal inhibitors, geldanamycin and radicicol. Glutathione and other reducing agents partially blocked geldanamycin-induced acceleration of cell lysis but were largely ineffective with other inhibitors. Indeed, geldanamycin treatment led to superoxide production and a change in membrane fluidity. When Hsp90 content was diminished using anti-Hsp90 hammerhead ribozymes, an accelerated cell lysis was also observed. Hsp90 inhibition-induced cell lysis was more pronounced in eukaryotic (yeast, mouse red blood, and human T-lymphoma) cells than in bacteria. Our results indicate that besides the geldanamycin-induced superoxide production, and a consequent increase in cell lysis, inhibition or lack of Hsp90 alone can also compromise cellular integrity. Moreover, cell lysis after hypoxia and complement attack was also enhanced by any type of Hsp90 inhibition used, which shows that the maintenance of cellular integrity by Hsp90 is important in physiologically relevant lytic conditions of tumor cells.