This document presents recommendations of the American Association of Physicists in Medicine (AAPM) for quality assurance of computed-tomography- (CT) simulators and CT-simulation process. This report was prepared by Task Group No. 66 of the AAPM Radiation Therapy Committee. It was approved by the Radiation Therapy Committee and by the AAPM Science Council.

The efficacy of stereotactic body radiotherapy (SBRT) has been well demonstrated. However, it presents unique challenges for accurate planning and delivery especially in the lungs and upper abdomen where respiratory motion can be significantly confounding accurate targeting and avoidance of normal tissues. In this paper we review the current literature on SBRT for lung and upper abdominal tumors with particular emphasis on addressing respiratory motion and its affects. We provide recommendations on strategies to manage motion for different, patient specific situations. Some of the recommendations will potentially be adopted to guide clinical trial protocols.

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Exposure of mammalian cells to DNA damage-inducing agents (DDIA) inhibits ongoing DNA replication. The molecular mechanism of this inhibition remains to be elucidated. We employed a simian virus 40 (SV40) based in vitro DNA replication assay to study biochemical aspects of this inhibition. We report here that the reduced DNA replication activity in extracts of DDIA-treated cells is partly caused by a reduction in the amount of replication protein A (RPA). We also report that the dominant inhibitory effect is caused by the DNAdependent protein kinase (DNA-PK) which inactivates SV40 T antigen (TAg) by phosphorylation. The results demonstrate that RPA and DNA-PK are involved in the regulation of viral DNA replication after DNA damage and suggest that analogous processes regulate cellular DNA replication with the DNA-PK targeting the functional homologues of TAg.Inhibition of DNA replication in eukaryotic cells is one of the earliest effects of radiation to be reported. Camptothecin (CPT) 1 and other DNA damage-inducing agents (DDIA) exert similar inhibitory effects on DNA replication in actively growing cells. It has been documented that a major component of this inhibition derives from a delay in the initiation of unreplicated origins (1, 2). Although this response was first observed several decades ago, the underlying molecular mechanisms remain largely unknown but ATM is thought to play an important role. More recently, evidence has been presented suggesting that the inhibition observed in DNA replication in response to DDIA is equivalent to the activation of a checkpoint in the S-phase and that it requires in yeast the products of MEC1 and RAD53 genes, homologues of ATM and Chk2,. It is important to establish the mechanisms of regulation of DNA replication after DNA damage and the biochemical functions of the above genes in the process. We investigated the regulation of DNA replication after DNA damage using a simian virus 40 (SV40) based in vitro DNA replication assay, and have shown that extracts of cells exposed to DDIA have reduced activity for in vitro DNA replication and inhibit, in a dominant fashion, the ability of extracts from nontreated cells to promote in vitro DNA replication (7,8).In the SV40-based DNA replication assay, replication of plasmids containing the SV40 origin of DNA (ori ϩ DNA) replication is accomplished in vitro with either crude cytoplasmic extracts or proteins purified from such extracts with SV40 T antigen (TAg) as the only noncellular protein (9 -13). It is believed that all cellular proteins required in this assay function in a manner similar to that in vivo (10 -14). We have reported that the degree of inhibition of DNA replication in cells exposed either to x-rays or CPT is comparable with that measured in vitro using extracts prepared from cells exposed to these agents (7,8). We subsequently focused on the molecular characterization of this inhibition. In the present study, we provide evidence that following DNA damage two processes contribute to the inhibition of in vitro ...

We conclude that irradiation before puberty has a severe detrimental effect on outgrowth of seminiferous tubules. But, within the seminiferous epithelium, spermatogenetic recovery occurs at a low rate with no detectable relation to the maturity of the epithelium at irradiation. We also show that autologous testis cell transplantation can enhance spermatogenesis, but only in isolated cases.

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The acute lethality of total-body irradiation (TBI) involves damage to multiple organs, including bone marrow and intestine. Ionizing radiation mitigators that are effective when delivered 24 h or later after TBI include the anti-apoptotic drug, JP4-039 and the anti-necroptotic drug, necrostatin-1. In contrast to effective delivery of JP4-039 at 24 h after TBI, necrostatin-1 is most effective when delivery is delayed until 48 h, a time that correlates with the elevation of necroptosis-inducing inflammatory cytokines and necroptosis-induced serine phosphorylation of receptor-interacting serine/threonine-protein kinase-3 (RIP3) in tissues. The goal of this work was to determine whether administration of JP4-039 influenced the optimal delivery time for necrostatin-1. We measured daily levels of 33 proteins in plasma compared to intestine and bone marrow of C57BL/6NTac female mice over a 7-day time period after 9.25 Gy TBI (LD). Protein responses to TBI in plasma were different from those measured in intestine or bone marrow. In mice that were given JP4-039 at 24 h after TBI, we delayed necrostatin-1 delivery for 72 h after TBI based on measured delay in RIP-3 kinase elevation in marrow and intestine. Sequential delivery of these two radiation mitigator drugs significantly increased survival compared to single drug administration.