Shaking the family tree: identification of novel and biologically active alternatively spliced isoforms across the KLF family of transcription factors.

Alternative splicing represents a unique post-transcriptional mechanism that increases the complexity of the eukaryotic proteome-generating protein isoforms whose functions can be novel, diverse, and/or even antagonistic when compared to its full-length transcript. The KLF family of genes consists of ≥17 members, which are involved in the regulation of numerous critical cellular processes, including differentiation, cell proliferation, growth-related signal transduction, angiogenesis, and apoptosis. Using a strategy based on RT-PCR, selective cloning, and promoter-based assays of cancer-relevant genes, we identify and characterize the existence of multiple biologically active KLF splice forms across the entire family of proteins. We demonstrate biological function for a number of these isoforms. Furthermore, we highlight a possible functional interaction between full-length KLF4 and one of its splice variants in up-regulating cellular proliferation. Taken together, this report identifies for the first time a more complete view of the genomic and proteomic breadth and complexity of the KLF transcription factor family, revealing the existence of highly expressed and biologically active isoforms previously uncharacterized. In essence, knowing that these KLF isoforms exist provides the first step toward understanding the roles of these genes in human health and disease.

Pentoxifylline in prevention of radiation-induced lung toxicity in patients with breast and lung cancer: a double-blind randomized trial.

PURPOSE: Pentoxifylline (Ptx) is thought to be helpful in preventing radiotoxicity by inhibiting platelet aggregation and tumor necrosis factor. We assessed whether prophylactic use of Ptx could prevent early and late normal lung tissue damage due to radiotherapy in a double-blind, randomized trial. METHODS AND MATERIALS: A total of 40 patients with lung or breast cancer were randomized to receive Ptx (400 mg) or a placebo, 3 times daily, during the entire period of radiotherapy. We used the late effects normal tissue-subjective, objective, management, and analytic (LENT-SOMA) scale to evaluate and compare toxicity, including the findings of pulmonary function tests and radiologic and scintigraphic evaluations performed before and at 3 and 6 months of follow-up. RESULTS: According to the LENT score, a statistically significant difference was found between the two groups in favor of Ptx (p = 0.016). The difference in diffusing capacity of the lung for carbon monoxide and regional perfusion scan results were found to be statistically significant between the groups at 3 and 6 months (p <0.05). The use of Ptx resulted in a noticeable reduction in the higher degrees of lung injury detected radiologically. CONCLUSION: Our study showed a significant protective effect of Ptx for both early and late lung radiotoxicity. We recommend the prophylactic use of Ptx, finding it to be safe and effective.