One of the challenges presented by chemotherapy toxicity occurring after marrow transplantation is its histologic similarity to skin GVHD. However, chemoradiation toxicity was not associated with findings diagnostic of histologic GVHD after 20 days posttransplantation. Others have also found that keratinocyte dysplasia was not associated with the onset of aGVHD. Our data suggest that SKD is Voriconazole not associated with clinical GVHD but is associated with histologic GVHD. It is evident from Table 3 that a busulfan preparative regimen fails to be associated with histologic GVHD. This leaves open the possibility that histologic GVHD may tend to be diagnosed in the presence of concurrent SKD. Table 3 also implies that histologic GVHD was sometimes diagnosed in the absence of clinicalGVHD.
This is a widely reported phenomenon, presumably because of the relatively low specificity of the histologic criteria. Further conclusions regarding GVHD are beyond the power of this case control study of SKD,What happens to severe keratinocyte dysplasia?, The time course ofSKDwas studied by evaluating subsequent skin biopsies, Leflunomide Arava when available. A statistical treatment was not attempted. It turned out that SKD resolved rapidly, appearing as slight dysplasia in 32 days on average and moderate atypia in 45 days. Normal histology was reached only slowly, however, after an average of 241 days following the index biopsy. The conclusion that SKD reverts gradually to normal histology over several months is warranted.
In summary, our study has provided evidence that severe Vorinostat MK-0683 keratinocyte dysplasia is an occasional histologic finding in day 28 to 84 of the posttransplantation period of HSCT patients, with a frequency of 9%of the biopsies, 12%of the biopsied patients, and 16%of biopsied patients prepared with a busulfan containing conditioning regimen. Preparation DNA-PK inhibition for transplantation with busulfan was independently and very strongly associated with SKD. Familiarity with this potential association is important for the correct diagnosis when evaluating biopsies from this particular patient population.The treatment of solid tumors with targeted agents has shown promise, particularly with inhibitors of the epidermal growth factor receptor and angiogenic pathways. Enzastaurin, a novel targeted agent in the class of acyclic N bisindolylmaleimides, is an oral serine/threonine kinase inhibitor that targets both the protein kinase C and AKT pathways.
PKC and AKT have been associated with tumorigenesis, treatment efficacy, and outcome in a variety of cancers, including non small cell lung cancer. In preclinical models, anti tumor and anti angiogenic activity of enzastaurin was demonstrated in various cancer cell lines and human cancer reasoning xenografts and, in clinical studies, enzastaurin as a single agent was well tolerated up to 700 mg with early promising activity. In a phase II study, single agent enzastaurin as secondor third line therapy in patients with metastatic NSCLC was well tolerated with some disease stabilization seen. Erlotinib, an EGFR targeted tyrosine kinase inhibitor, has been shown to increase overall survival when combined with gemcitabine in pancreatic cancer and as a second or third line single agent in NSCLC. In NSCLC, erlotinib increased the response rate.