Combined Modality Therapies for High-Risk Prostate Cancer: Narrative Review of Current Understanding and New Directions.

Despite the many prospective randomized trials that have been available in the past decade regarding the optimization of radiation, hormonal, and surgical therapies for high-risk prostate cancer (PCa), many questions remain. There is currently a lack of level I evidence regarding the relative efficacy of radical prostatectomy (RP) followed by adjuvant radiation compared to radiation therapy (RT) combined with androgen deprivation therapy (ADT) for high-risk PCa. Current retrospective series have also described an improvement in biochemical outcomes and PCa-specific mortality through the use of augmented radiation strategies incorporating brachytherapy. The relative efficacy of modern augmented RT compared to RP is still incompletely understood. We present a narrative review regarding recent advances in understanding regarding comparisons of overall and PCa-specific mortality measures among patients with high-risk PCa treated with either an RP/adjuvant RT or an RT/ADT approach. We give special consideration to recent trends toward the assembly of multi-institutional series targeted at providing high-quality data to minimize the effects of residual confounding. We also provide a narrative review of recent studies examining brachytherapy boost and systemic therapies, as well as an overview of currently planned and ongoing studies that will further elucidate strategies for treatment optimization over the next decade

The Impact of Prostate Cancer Treatment on Quality of Life: A Narrative Review with a Focus on Randomized Data.

Despite excellent oncologic outcomes, the management of localized prostate cancer remains complex and is dependent on multiple factors, including patient life expectancy, medical comorbidities, tumor characteristics, and genetic risk factors. Decades of iterative clinical trials have improved the optimization and utilization of surgical and radiation-based modalities, as well as their combinatorial use with anti-androgen and systemic therapies. While cure rates are high and converging on equivalent disease control should an upfront surgical or radiotherapeutic approach be optimized, the long-term side effects of surgical and radiation-based treatments can differ significantly in nature. Decisions regarding the selection of therapy are therefore best made in an informed and shared medical decision-making process between clinician and patient with respect to cancer control as well as adverse effects. We outline in this narrative review an understanding regarding implications of surgical and radiation treatment on quality of life after treatment, and how these data may be considered in the context of advising patients regarding the selection of therapy. This narrative review largely focuses on the quality of life data obtained from prospective randomized trials of men treated for prostate cancer. We believe this provides the best assessment of the quality of life and can be used to inform patients when making treatment decisions

Generating topological order from a 2D cluster state using a duality mapping

In this paper we prove, extend and review possible mappings between the two-dimensional Cluster state, Wen's model, the two-dimensional Ising chain and Kitaev's toric code model. We introduce a two-dimensional duality transformation to map the two-dimensional lattice cluster state into the topologically-ordered Wen model. Then, we subsequently investigates how this mapping could be achieved physically, which allows us to discuss the rate at which a topologically ordered system can be achieved. Next, using a lattice fermionization method, Wen's model is mapped into a series of one-dimensional Ising interactions. Considering the boundary terms with this mapping then reveals how the Ising chains interact with one another. The relationships discussed in this paper allow us to consider these models from two different perspectives: From the perspective of condensed matter physics these mappings allow us to learn more about the relation between the ground state properties of the four different models, such as their entanglement or topological structure. On the other hand, we take the duality of these models as a starting point to address questions related to the universality of their ground states for quantum computation.Comment: 5 Figure

Quantum memories at finite temperature

To use quantum systems for technological applications one first needs to preserve their coherence for macroscopic time scales, even at finite temperature. Quantum error correction has made it possible to actively correct errors that affect a quantum memory. An attractive scenario is the construction of passive storage of quantum information with minimal active support. Indeed, passive protection is the basis of robust and scalable classical technology, physically realized in the form of the transistor and the ferromagnetic hard disk. The discovery of an analogous quantum system is a challenging open problem, plagued with a variety of no-go theorems. Several approaches have been devised to overcome these theorems by taking advantage of their loopholes. The state-of-the-art developments in this field are reviewed in an informative and pedagogical way. The main principles of self-correcting quantum memories are given and several milestone examples from the literature of two-, three- and higher-dimensional quantum memories are analyzed

Prevention and Mitigation of Acute Radiation Syndrome in Mice by Synthetic Lipopeptide Agonists of Toll-Like Receptor 2 (TLR2)

Bacterial lipoproteins (BLP) induce innate immune responses in mammals by activating heterodimeric receptor complexes containing Toll-like receptor 2 (TLR2). TLR2 signaling results in nuclear factor-kappaB (NF-κB)-dependent upregulation of anti-apoptotic factors, anti-oxidants and cytokines, all of which have been implicated in radiation protection. Here we demonstrate that synthetic lipopeptides (sLP) that mimic the structure of naturally occurring mycoplasmal BLP significantly increase mouse survival following lethal total body irradiation (TBI) when administered between 48 hours before and 24 hours after irradiation. The TBI dose ranges against which sLP are effective indicate that sLP primarily impact the hematopoietic (HP) component of acute radiation syndrome. Indeed, sLP treatment accelerated recovery of bone marrow (BM) and spleen cellularity and ameliorated thrombocytopenia of irradiated mice. sLP did not improve survival of irradiated TLR2-knockout mice, confirming that sLP-mediated radioprotection requires TLR2. However, sLP was radioprotective in chimeric mice containing TLR2-null BM on a wild type background, indicating that radioprotection of the HP system by sLP is, at least in part, indirect and initiated in non-BM cells. sLP injection resulted in strong transient induction of multiple cytokines with known roles in hematopoiesis, including granulocyte colony-stimulating factor (G-CSF), keratinocyte chemoattractant (KC) and interleukin-6 (IL-6). sLP-induced cytokines, particularly G-CSF, are likely mediators of the radioprotective/mitigative activity of sLP. This study illustrates the strong potential of LP-based TLR2 agonists for anti-radiation prophylaxis and therapy in defense and medical scenarios

Assessing the Effects of Responsible Leadership and Ethical Conflict on Behavioral Intention

[[abstract]]This study develops a research model that elaborates how responsible leadership and ethical conflict influence employees from the perspectives of role theory and attachment theory. Its empirical results reveal that turnover intention indirectly relates to ethical conflict and responsible leadership via the mediating mechanisms of organizational identification and organizational uncertainty. At the same time, helping intention indirectly relates to ethical conflict and responsible leadership only through organizational identification. Finally, the managerial implications for international business and research limitations based on the empirical results are discussed.[[notice]]補正完

Combined Effect of Histone Acetylation and Acetyl Mark Readers on Radiation Sensitivity

We are interested in studying potential drugs that have the ability to make tumors more sensitive to radiation. There has been much interest in examining the effect of modulation to chromatin structure on the DNA damage response (DDR). We therefore examined histone deacetylase (HDAC) inhibitors, small molecules that modify the structural features of chromatin involved in the packaging of DNA. HDAC inhibitors are considered to be potential drug candidates to complement radiation therapy, yet the mechanisms underlying their effects have been elusive. To study the DDR signaling effects of HDAC inhibitors, we developed a high-throughput automated microscopy assay to assess effects on elements of DNA damage-mediated signaling through quantification of H2AX phosphorylation, cell cycle profiling, and cell survival following irradiation. We then applied this assay to a library of diverse HDAC inhibitors as well as a collection of shRNAs targeting the individual HDACs. We next assessed DSB induction and repair kinetics on a selection of active HDAC inhibitors with CometChip, a novel high-throughput adaptation of the single-cell DSB comet assay. Finally, with the recent discovery of the role of the bromodomain chromatin reader protein Brd4 in the insulation of chromatin from the DDR, we explored combinatorial use of HDACi and JQ1 to achieve altered DDR through simultaneous alteration of chromatin structure and acetyl-lysine reading. Our data suggest that class I HDAC inhibitors potently elevate H2AX phosphorylation, but without strong effects on DSB induction or repair kinetics. We find that many HDAC inhibitors also enhance G2/M cell cycle arrest and decrease proliferation, even in the absence of irradiation. These data suggest that HDAC inhibitors influence radiation effects primarily through altering DNA damage-induced signaling events. We have also found that overexpression of specific Brd4 isoforms can abrogate the elevated H2AX phosphorylation induced by HDAC inhibition and lead to preferential cell death. This may have important implications for the clinical use of these agents

Radioprotection In Vitro and In Vivo by Minicircle Plasmid Carrying the Human Manganese Superoxide Dismutase Transgene

Manganese superoxide dismutase plasmid liposomes (MnSOD-PL) confer organ-specific in vivo ionizing irradiation protection. To prepare for potential intravenous clinical trials of systemic MnSOD-PL for radioprotection in humans, plasmid and bacterial sequences were removed and a new minicircle construct was tested. Minicircle MnSOD was purified and then cotransfected into 32D cl 3 murine interleukin-3-dependent hematopoietic progenitor cells along with another plasmid carrying the neo gene. Cells were selected in G418 (50 μg/ml) and cloned by limiting dilution. Biochemical analysis of minicircle MnSOD-transfected cells showed an MnSOD biochemical activity level of 5.8 ± 0.5 U/mg compared with 2.7 ± 0.1 U/mg for control 32D cl 3 cells (p = 0.0039). 32D-mc-MnSOD cells were as radioresistant as full-length MnSOD-PL transgene-expressing 2C6 cells, relative to 32D cl 3 parent cells, with an increased shoulder on the radiation survival curve (\documentclass{aastex}\usepackage{amsbsy}\usepackage{amsfonts}\usepackage{amssymb}\usepackage{bm}\usepackage{mathrsfs}\usepackage{pifont}\usepackage{stmaryrd}\usepackage{textcomp}\usepackage{portland,xspace}\usepackage{amsmath,amsxtra}\pagestyle{empty}\DeclareMathSizes{10}{9}{7}{6}\begin{document} $${\overline n} = 4.8 \pm 0.2$$ \end{document} and \documentclass{aastex}\usepackage{amsbsy}\usepackage{amsfonts}\usepackage{amssymb}\usepackage{bm}\usepackage{mathrsfs}\usepackage{pifont}\usepackage{stmaryrd}\usepackage{textcomp}\usepackage{portland,xspace}\usepackage{amsmath,amsxtra}\pagestyle{empty}\DeclareMathSizes{10}{9}{7}{6}\begin{document}$${\overline n} = 4.6 \pm 0.2$$ \end{document}, respectively, compared with 1.5 ± 0.5 for 32D cl 3 cells; p = 0.007). C57BL/6NHsd mice received intraoral mc-MnSOD-PL, mc-DsRed-PL control, full-length MnSOD-PL, or blank-PL and then were irradiated 24 hr later with 31 Gy to the esophagus. Mice receiving mc-MnSOD-PL showed increased survival compared with control mice or mice treated with mc-DsRed-PL (p = 0.0003 and 0.039, respectively), and comparable to full-length MnSOD-PL. Intravenous, systemic administration of mc-MnSOD-PL protected mice from total body irradiation (9.75 Gy). Therefore, minicircle DNA containing the human MnSOD transgene confers undiminished radioprotection in vitro and in vivo