Multi-Institutional Data Collection and Analysis via the Pediatric Proton/Photon Consortium Registry

Care of patients with proton therapy has increased in the past decade. It is important to report on outcomes and disease specific utilization of particle therapy. In this chapter, we review our experience in developing a registry for pediatric patients treated with radiation to assess outcomes and provide a platform for shared research interests

Neutron diffraction studies towards deciphering the protonation state of catalytic residues in the bacterial KDN9P phosphatase

The enzyme 2-keto-3-deoxy-9-O-phosphonononic acid phosphatase (KDN9P phosphatase) functions in the pathway for the production of 2-keto-3-deoxy-d-­glycero-d-galacto-nononic acid, a sialic acid that is important for the survival of commensal bacteria in the human intestine. The enzyme is a member of the haloalkanoate dehalogenase superfamily and represents a good model for the active-site protonation state of family members. Crystals of approximate dimensions 1.5 × 1.0 × 1.0 mm were obtained in space group P2(1)2(1)2, with unit-cell parameters a = 83.1, b = 108.9, c = 75.7 Å. A complete neutron data set was collected from a medium-sized H/D-exchanged crystal at BIODIFF at the Heinz Maier-Leibnitz Zentrum (MLZ), Garching, Germany in 18 d. Initial refinement to 2.3 Å resolution using only neutron data showed significant density for catalytically important residues

Engineering Encodable Lanthanide-Binding Tags into Loop Regions of Proteins

Lanthanide-binding tags (LBTs) are valuable tools for investigation of protein structure, function, and dynamics by NMR spectroscopy, X-ray crystallography, and luminescence studies. We have inserted LBTs into three different loop positions (denoted L, R, and S) of the model protein interleukin-1β (IL1β) and varied the length of the spacer between the LBT and the protein (denoted 1−3). Luminescence studies demonstrate that all nine constructs bind Tb3+ tightly in the low nanomolar range. No significant change in the fusion protein occurs from insertion of the LBT, as shown by two X-ray crystallographic structures of the IL1β-S1 and IL1β-L3 constructs and for the remaining constructs by comparing the 1H−15N heteronuclear single-quantum coherence NMR spectra with that of the wild-type IL1β. Additionally, binding of LBT-loop IL1β proteins to their native binding partner in vitro remains unaltered. X-ray crystallographic phasing was successful using only the signal from the bound lanthanide. Large residual dipolar couplings (RDCs) could be determined by NMR spectroscopy for all LBT-loop constructs and revealed that the LBT-2 series were rigidly incorporated into the interleukin-1β structure. The paramagnetic NMR spectra of loop-LBT mutant IL1β-R2 were assigned and the Δχ tensor components were calculated on the basis of RDCs and pseudocontact shifts. A structural model of the IL1β-R2 construct was calculated using the paramagnetic restraints. The current data provide support that encodable LBTs serve as versatile biophysical tags when inserted into loop regions of proteins of known structure or predicted via homology modeling.National Science Foundation (U.S.) (Grant MCB 0744415)Ruth L. Kirschstein National Research Service AwardUnited States. Dept. of Energy (Offices of Biological and Environmental Research and of Basic Energy Sciences)National Institutes of Health (U.S.) (National Center for Research Resources

Radiation Therapy for Small Cell Lung Cancer: An ASTRO Clinical Practice Guideline

Purpose: Several sentinel phase III randomized trials have recently been published challenging traditional radiation therapy (RT) practices for small cell lung cancer (SCLC). This American Society for Radiation Oncology guideline reviews the evidence for thoracic RT and prophylactic cranial irradiation (PCI) for both limited-stage (LS) and extensive-stage (ES) SCLC. Methods: The American Society for Radiation Oncology convened a task force to address 4 key questions focused on indications, dose fractionation, techniques and timing of thoracic RT for LS-SCLC, the role of stereotactic body radiation therapy (SBRT) compared with conventional RT in stage I or II node negative SCLC, PCI for LS-SCLC and ES-SCLC, and thoracic consolidation for ES-SCLC. Recommendations were based on a systematic literature review and created using a consensus-building methodology and system for grading evidence quality and recommendation strength. Results: The task force strongly recommends definitive thoracic RT administered once or twice daily early in the course of treatment for LS-SCLC. Adjuvant RT is conditionally recommended in surgically resected patients with positive margins or nodal metastases. Involved field RT delivered using conformal advanced treatment modalities to postchemotherapy volumes is also strongly recommended. For patients with stage I or II node negative disease, SBRT or conventional fractionation is strongly recommended, and chemotherapy should be delivered before or after SBRT. In LS-SCLC, PCI is strongly recommended for stage II or III patients who responded to chemoradiation, conditionally not recommended for stage I patients, and should be a shared decision for patients at higher risk of neurocognitive toxicities. In ES-SCLC, radiation oncologist consultation for consideration of PCI versus magnetic resonance surveillance is strongly recommended. Lastly, the use of thoracic RT is strongly recommended in select patients with ES-SCLC after chemotherapy treatment, including a conditional recommendation in those responding to chemotherapy and immunotherapy. Conclusions: RT plays a vital role in both LS-SCLC and ES-SCLC. These guidelines inform best clinical practices for local therapy in SCLC