Regulation of Ikaros function by casein kinase 2 and protein phosphatase 1

The Ikaros gene encodes a zinc finger,DNA-binding protein that regulates gene transcription and chromatin remodeling.Ikaros is a master regulator of hematopoiesis and an established tumor suppressor.Moderate alteration of Ikaros activity (e.g.haploinsufficiency) appears to be sufficient to promote malignant transformation in human hematopoietic cells.This raises questions about the mechanisms that normally regulate Ikaros function and the potential of these mechanisms to contribute to the development of leukemia.The focus of this review is the regulation of Ikaros function by phosphorylation/dephosphorylation.Site-specific phosphorylation of Ikaros by casein kinase 2 (CK2) controls Ikaros DNA-binding ability and subcellular localization.As a consequence,the ability of Ikaros to regulate cell cycle progression,chromatin remodeling,target gene expression,and thymocyte differentiation are controlled by CK2.In addition,hyperphosphorylation of Ikaros by CK2 leads to decreased Ikaros levels due to ubiquitinmediated degradation.Dephosphorylation of Ikaros by protein phosphatase 1 (PP1) acts in opposition to CK2 to increase Ikaros stability and restore Ikaros DNA binding ability and pericentromeric localization.Thus,the CK2 and PP1 pathways act in concert to regulate Ikaros activity in hematopoiesis and as a tumor suppressor.This highlights the importance of these signal transduction pathways as potential mediators of leukemogenesis via their role in regulating the activities of Ikaros.

Radiation-Induced Spinal Glioblastoma Multiforme: A Rare Complication in the Management of Head and Neck Cancer

Background: Radiation-induced gliomas of the spinal cord are rare late complications of spinal cord irradiation that typically occur in patients treated at younger ages. Aim: Raise awareness of radiation induced high grade gliomas with a case presentation and a review of the literature. Case Presentation: A 50-year-old male with Stage IVA squamous cell carcinoma of the oropharynx was treated with external beam radiotherapy with a complete response. Seven years later, he presented with a cervical spinal cord mass on MRI. An open biopsy was performed. Pathology revealed an intramedullary WHO grade IV astrocytoma, (i.e., glioblastoma multiforme) of the cervical spine that fulfilled the criteria for a radiation-induced malignancy. Conclusions : Review of the literature suggests that radiation-induced gliomas tend to be high grade and may occur at the periphery of an irradiated field. Radiation-induced gliomas of the spinal cord are a serious complication of radiotherapy that may occur in older patients with head and neck cancers, but are so rare that it should not affect treatment decisions.

Network analyses:Inhibition of androgen receptor signaling reduces inflammation in the lung through AR-MAF-IL6 signaling axes

Androgen receptor(AR)is a major transcription factor that plays a role in inflammatory response including interleukin-6(IL6)signaling.1 While AR regulation through paracrine loop signaling in prostate tissue is well-studied,its impact through an IL6 autocrine loop in the lung has not been wellstudied despite the organ's response to respiratory viral infection.Chemical inhibition and RNA knockdown of AR identified a bZIP transcription factor MAF to be a common target of inflammation using these perturbations in lung cells.

TrueBeam Low Dose Rate Investigation for Pulsed Reduced Dose Rate IMRT

The capability of the TrueBeam treatment system to deliver step and shoot IMRT plans at low dose rates was evaluated. Beam characteristics during low dose rates (5 to 100 MU/min) were evaluated for consistency using a planar ion chamber array. MU constancy, linearity, and beam profile symmetry were all found to be equivalent within 0.5%. The response of the Scandi Dos Delta 4 system was also evaluated at low dose rates of using static open beams compared to ion chamber measurements, and step and shoot IMRT plans comparing 5 - 20 MU/min and 100 MU/min dose rates, with a maximum observed absolute dose difference of 0.8% and equivalence margin of 0.2%. The Gamma Index and measurement reproducibility were also found to be equivalent.

Unraveling the molecular genetics of head and neck cancer through genome-wide approaches

The past decade has seen an unprecedented increase in our understanding of the biology and etiology of head and neck squamous cell carcinomas(HNSCC).Genome-wide sequencing projects have identified a number of recurrently mutated genes,including unexpected alterations in the NOTCH pathway and chromatin related genes.Gene-expression profiling has identified 4 distinct genetic subtypes which show some parallels to lung squamous cell carcinoma biology.The identification of the human papilloma virus as one causative agent in a subset of oropharyngeal cancers and their association with a favorable prognosis has opened up avenues for new therapeutic strategies.The expanding knowledge of the underlying molecular abnormalities in this once very poorly understood cancer should allow for increasingly rational clinical trial design and improved patient outcomes.