Spacer application was well tolerated. Increased perirectal space reduced rectal irradiation, reduced rectal toxicity severity, and decreased rates of patients experiencing declines in bowel quality of life. The spacer appears to be an effective tool, potentially enabling advanced prostate RT protocols.

The benefit of a hydrogel spacer in reducing the rectal dose, toxicity, and QOL declines after image guided intensity modulated radiation therapy for prostate cancer was maintained or increased with a longer follow-up period, providing stronger evidence for the benefit of hydrogel spacer use in prostate radiation therapy.

The t(9;22) chromosomal translocation results in expression of P210 BCR-ABL , a fusion protein necessary for the development of chronic myelogenous leukemia (CML). The constitutive activation of the P210 BCR-ABL tyrosine kinase results in phosphorylation of multiple signaling pathways leading to the transformed phenotype. Additionally, extracellular interactions between P210 BCR-ABL -expressing progenitor cells and bone marrow stroma may provide external signals that facilitate CML development. In contrast to the intracellular signaling pathways involved in CML, little is known about how P210 BCR-ABL expression modifies cell-cell and cellsubstratum interactions. To investigate the role of P210 BCR-ABL in modulating cellular adhesion, we used a highly sensitive and quantitative cell detachment apparatus that measures the strength of association between a population of cells and an adhesive matrix. Our findings show that P210 BCR-ABL expression increased adhesion nearly 2-fold between the myeloblastic cell line, 32D, and fibronectin compared to a control vector. We then investigated whether abnormal adhesion due to P210 BCR-ABL expression was caused by its tyrosine kinase activity. A quantitative analysis of cell-fibronectin adhesion found that neither expression of a kinase- IntroductionP210 BCR-ABL is a 210-kd nonreceptor tyrosine kinase that is the product of the t(9;22) balanced translocation between the bcr gene on chromosome 22 and the abl gene on chromosome 9. 1 The translocation results in the formation of the Philadelphia chromosome (Ph), which is the diagnostic marker for chronic myelogenous leukemia (CML), a disease characterized by abnormal accumulation of hematopoietic cells in the bone marrow, elevated peripheral white blood cell counts, and defective progenitor-stromal adhesion in vitro. 2,3 There is intense interest in the observation that P210 BCR-ABL expression in cell lines and bone marrow progenitor cells leads to defective cell binding to fibronectin and stromal cells because abnormal adhesion in transformed cells may contribute to loss of contact inhibition and proliferation in the bone marrow of patients with CML. 3-5 However, the mechanism by which P210 BCR-ABL alters cellular adhesion is poorly understood.P210 BCR-ABL is primarily found in the cytoplasm and colocalizes with actin through a C-terminal actin-binding domain. 6,7 It is unknown if P210 BCR-ABL directly modifies actin or recruits signaling molecules to the cytoskeleton. However, transformed cells exhibit increased motility and enhanced membrane ruffling and proteins of the focal adhesion complex, such as focal adhesion kinase and paxillin, are phosphorylated in P210 BCR-ABL cells. 8,9 Together, these observations suggest that P210 BCR-ABL induces abnormal cell-substratum binding that is likely involved in the pathogenesis of CML. One possible mechanism is that P210 BCR-ABL regulates an inside-out signaling pathway that stimulates integrinmediated adhesion in a manner similar to growth factors, such as interleukin 3 (IL-3). 10 T...

The FiberWire-button implant may not maintain adequate ankle syndesmotic reduction in the immediate post-operative period relative to a metallic screw.