No abstract

Tumor metastasis is the major cause of morbidity and mortality in patients with breast cancer. It is critical to identify metastasis enabling genes and understand how they are responsible for inducing specific aspects of the metastatic phenotype to allow for improved clinical detection and management. Protein kinase CE (PKCE), a member of a family of serine/threonine protein kinases, is a transforming oncogene that has been reported to be involved in cell invasion and motility. In this study, we investigated the role of PKCE in breast cancer development and progression. High-density tissue microarray analysis showed that PKCE protein was detected in 73.6% (106 of 144) of primary tumors from invasive ductal breast cancer patients. Increasing PKCE staining intensity was associated with high histologic grade (P = 0.0206), positive Her2/neu receptor status (P = 0.0419), and negative estrogen (P = 0.0026) and progesterone receptor status (P = 0.0008). Kaplan-Meier analyses showed that PKCE was significantly associated with poorer disease-free and overall survival (log-rank, P = 0.0478 and P = 0.0414, respectively). RNA interference of PKCE in MDA-MB231 cells, an aggressive breast cancer cell line with elevated PKCE levels, resulted in a cell phenotype that was significantly less proliferative, invasive, and motile than the parental or the control RNA interference transfectants. Moreover, in vivo tumor growth of small interfering RNA-PKCE MDA-MB231 clones was retarded by a striking 87% (P < 0.05) and incidence of lung metastases was inhibited by 83% (P < 0.02). PKCEdeficient clones were found to have lower RhoC GTPase protein levels and activation. Taken together, these results revealed that PKCE plays a critical and causative role in promoting an aggressive metastatic breast cancer phenotype and as a target for anticancer therapy. (Cancer Res 2005; 65(18): 8366-71)

ObjectivesRecurrent respiratory papillomatosis (RRP) is a chronic disease of the respiratory tract that occurs in both children and adults. It is caused by the human papillomavirus (HPV), in particular low‐risk HPV6 and HPV11, and aggressiveness varies among patients. RRP remains a chronic disease that is difficult to manage. This review provides perspectives on current and future management of RRP.ResultsThe current standard of care is surgical excision, with adjuvant therapies as needed. Surgical management of RRP has evolved with the introduction of microdebriders and photoangiolytic lasers; the latter can now be used in the office setting. Numerous adjuvant pharmacologic therapies have been utilized with some success. Also, exciting preliminary data show that HPV vaccines may prolong the time to recurrence in the RRP population. There is also optimism that wide‐spread HPV vaccination could reduce RRP incidence indirectly by preventing vertical HPV transmission to newborns.ConclusionTo date, the biology of RRP is not well understood, although it has been noted to become more aggressive in the setting of immune suppression. Additional research is needed to better understand immune system dysfunction in RRP such that immunomodulatory approaches may be developed for RRP management.Level of Evidence4