Prostate bed irradiation with alternative radio-oncological approaches (PAROS) - a prospective, multicenter and randomized phase III trial

Background: For patients with treatment-naïve carcinoma of the prostate, hypofractionated irradiation becomes more and more popular. Due to the low α/β value of prostate cancer, increased single dose leading to a shortened treatment period seems to be safe and feasible. However, reliable data is lacking for post-prostatectomy patients so far. Further, the role of proton therapy is still under debate. Two prospective phase II trials with both, hypofractionated photon and proton therapy, provided promising results. Methods/design: The PAROS trial is a prospective, multicenter and randomized phase III trial for men with localized prostate carcinoma after surgery. Post-prostatectomy patients will be randomized to either normofractionated radiotherapy (nRT) with photons (70.0/ 2.0 Gy), or hypofractionated radiotherapy (hRT) with photons (57.0/ 3.0 Gy) or hRT with protons (57.0/ 3.0 Gy relative biological effectiveness [RBE]). Block randomization is stratified by Gleason Score (≤ 7 vs. > 7) and treatment indication (adjuvant vs. salvage). The trial is planned to enroll 897 patients. The primary objective is to show an improvement in the bowel-score according to EORTC QLQ-PR25 after proton therapy compared to photon irradiation (week 12 vs. baseline). Secondary aims are non-inferiority of hRT compared to nRT with regard to biochemical progression-free survival (bPFS), overall survival (OS), quality of life and toxicity. Discussion: The present study aims to evaluate the role of hypofractionated radiotherapy to the prostate bed with photons and protons leading to significant impact on future management of operated men with prostate cancer. Trial registration: Deutsches Register klinischer Studien DRKS00015231; registered 27 September 2018

Induction of Cancer Cell Death by Isoflavone: The Role of Multiple Signaling Pathways

Soy isoflavones have been documented as dietary nutrients broadly classified as “natural agents” which plays important roles in reducing the incidence of hormone-related cancers in Asian countries, and have shown inhibitory effects on cancer development and progression in vitro and in vivo, suggesting the cancer preventive or therapeutic activity of soy isoflavones against cancers. Emerging experimental evidence shows that isoflavones could induce cancer cell death by regulating multiple cellular signaling pathways including Akt, NF-κB, MAPK, Wnt, androgen receptor (AR), p53 and Notch signaling, all of which have been found to be deregulated in cancer cells. Therefore, homeostatic regulation of these important cellular signaling pathways by isoflavones could be useful for the activation of cell death signaling, which could result in the induction of apoptosis of both pre-cancerous and/or cancerous cells without affecting normal cells. In this article, we have attempted to summarize the current state-of-our-knowledge regarding the induction of cancer cell death pathways by isoflavones, which is believed to be mediated through the regulation of multiple cellular signaling pathways. The knowledge gained from this article will provide a comprehensive view on the molecular mechanism(s) by which soy isoflavones may exert their effects on the prevention of tumor progression and/or treatment of human malignancies, which would also aid in stimulating further in-depth mechanistic research and foster the initiation of novel clinical trials

Lawson criterion for ignition exceeded in an inertial fusion experiment

For more than half a century, researchers around the world have been engaged in attempts to achieve fusion ignition as a proof of principle of various fusion concepts. Following the Lawson criterion, an ignited plasma is one where the fusion heating power is high enough to overcome all the physical processes that cool the fusion plasma, creating a positive thermodynamic feedback loop with rapidly increasing temperature. In inertially confined fusion, ignition is a state where the fusion plasma can begin "burn propagation" into surrounding cold fuel, enabling the possibility of high energy gain. While "scientific breakeven" (i.e., unity target gain) has not yet been achieved (here target gain is 0.72, 1.37 MJ of fusion for 1.92 MJ of laser energy), this Letter reports the first controlled fusion experiment, using laser indirect drive, on the National Ignition Facility to produce capsule gain (here 5.8) and reach ignition by nine different formulations of the Lawson criterion

Search for direct production of charginos and neutralinos in events with three leptons and missing transverse momentum in √s=7 TeV pp collisions with the ATLAS detector

A search for the direct production of charginos and neutralinos in final states with three electrons or muons and missing transverse momentum is presented. The analysis is based on 4.7 fb(-1) of root s = 7 TeV proton-proton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in three signal regions that are either depleted or enriched in Z-boson decays. Upper limits at 95% confidence level are set in R-parity conserving phenomenological minimal supersymmetric models and in simplified models, significantly extending previous results. (C) 2012 CERN. Published by Elsevier B.V. All rights reserved

Search for direct production of charginos and neutralinos in events with three leptons and missing transverse momentum in √s=7 TeV pp collisions with the ATLAS detector

A search for the direct production of charginos and neutralinos in final states with three electrons or muons and missing transverse momentum is presented. The analysis is based on 4.7 fb-1 of sqrt(s) = 7 TeV proton-proton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in three signal regions that are either depleted or enriched in Z-boson decays. Upper limits at 95% confidence level are set in R-parity conserving phenomenological minimal supersymmetric models and in simplified models, significantly extending previous results