ABSTRACT
OBJECTIVE: Assess the safety and feasibility of shortened hypofractionated high-dose palliative lung radiotherapy in a retrospective planning study. METHODS: Fifteen late stage (III or IV) NSCLC lung radiotherapy patients previously treated with the standard palliative 36 Gy in 12 fractions (12F) schedule were non-randomly selected to achieve a representative distribution of tumour sizes, volumes, and location. Plans were produced using 30 Gy in 5 fractions (5F) and 6 fractions (6F) using a 6MV FFF co-planar VMAT technique. Plans were optimised to meet dose-constraints for planning target volumes (PTVs) and organs at risk (OARs) with established OAR constraints expressed as biological equivalent doses (BEDs). The potential safety was assessed using these BEDs and also with reductions of 10% (BED-10%) and 20% (BED-20%) to account for a reduction in tolerance doses from the effects of chemotherapy or surgery. RESULTS: Mandatory BED constraints were met for all fifteen 5F and 6F plans; BED-10% constraints were met by all 6F plans and six 5F plans. BED-20% constraints were met by six 6F and three 5F respectively. CONCLUSION: It is potentially safe and feasible to deliver high-dose palliative radiotherapy for late stage NSCLC using the 5F or 6F regimes described, when planned to comparable OAR BEDs as standard radical techniques. It appears toxicity from these regimes should be within acceptable limits provided the dose-constraints described are met. A Phase II study is required to fully assess safety and feasibility, the outcomes of which could reduce the number of patient hospital visits for radiotherapy, thereby benefiting patients and optimising resource utilisation.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Radiotherapy, Intensity-Modulated , Humans , Radiotherapy Dosage , Retrospective Studies , Feasibility Studies , Radiotherapy, Intensity-Modulated/methods , Radiotherapy Planning, Computer-Assisted/methods , Carcinoma, Non-Small-Cell Lung/radiotherapy , Lung/pathology , Lung Neoplasms/radiotherapy , Organs at RiskABSTRACT
The insulin/insulin-like growth factor-1 (IGF-1) signaling system is a public regulator of aging in the model animals Caenorhabditis elegans, Drosophila melanogaster, and Mus musculus. For the first time, proteomic analyses of the environmentally resistant and 'nonaging' C. elegans dauer stage and long-lived daf-2 mutants has provided a unique insight into the protein changes which mediate survival against endogenously produced toxins. These changes support a diversion of energy consumption away from anabolic processes toward enhanced cellular maintenance and detoxification processes as previously described by the 'Green Theory of Aging'. Important components of this enhanced longevity system identified in this proteomics study include the alpha-crystallin family of small heat shock proteins, anti-ROS defense systems and cellular phase II detoxification (in daf-2 only). Among those proteins involved in phase II cellular detoxification that were significantly upregulated was a Pi-class glutathione transferase (GST) CE00302. Targeting this GST with RNAi revealed compensatory regulation within the Pi-class GSTs. Furthermore, a recombinant form of the GST protein was found to detoxify and/or bind short-chain aldehydic natural toxic products of lipid peroxidation and long-chained fatty-acids at physiologically relevant concentrations, which may indicate a role in longevity.
Subject(s)
Caenorhabditis elegans Proteins/genetics , Caenorhabditis elegans Proteins/metabolism , Caenorhabditis elegans/genetics , Caenorhabditis elegans/metabolism , Longevity/physiology , Mutation , Receptor, Insulin/genetics , Receptor, Insulin/metabolism , Analysis of Variance , Animals , Caenorhabditis elegans/chemistry , Cytosol/metabolism , Electrophoresis, Gel, Two-Dimensional , Glutathione S-Transferase pi/genetics , Glutathione S-Transferase pi/metabolism , Inactivation, Metabolic , Inhibitory Concentration 50 , Larva/metabolism , Longevity/genetics , Metabolic Networks and Pathways , RNA InterferenceABSTRACT
In this report, we describe the cloning, sequencing, and expression of the bovine orthologue of CD26 (BoCD26). Several monoclonal antibodies specific for a molecule, activation molecule 3 (ACT3), aberrantly expressed on superantigen-stimulated bovine CD8(+) lymphocytes, reacted with recombinant BoCD26 expressed in COS-7 and CHO cells. We also showed that human CD8(+) T cells stimulated by a superantigen expressed CD26 at high levels. These results demonstrate that ACT3 is identical to BoCD26 and suggest that CD26 upregulation on CD8(+) T cells is a general phenomenon of superantigens and not limited to their effects on bovine cells.