Superoxide dismutases (SODs) are necessary antioxidant enzymes that protect cells from reactive oxygen species (ROS). Decreased levels of SODs or mutations that affect their catalytic activity have serious phenotypic consequences. SODs perform their bio-protective role by converting superoxide into oxygen and hydrogen peroxide by cyclic oxidation and reduction reactions with the active site metal. Mutations of SODs can cause cancer of the lung, colon, and lymphatic system, as well as neurodegenerative diseases such as Parkinson’s disease and amyotrophic lateral sclerosis. While SODs have proven to be of significant biological importance since their discovery in 1968, the mechanistic nature of their catalytic function remains elusive. Extensive investigations with a multitude of approaches have tried to unveil the catalytic workings of SODs, but experimental limitations have impeded direct observations of the mechanism. Here, we focus on human MnSOD, the most significant enzyme in protecting against ROS in the human body. Human MnSOD resides in the mitochondrial matrix, the location of up to 90% of cellular ROS generation. We review the current knowledge of the MnSOD enzymatic mechanism and ongoing studies into solving the remaining mysteries.

A Review of the Catalytic Mechanism of Human Manganese Superoxide Dismutase

This review details and discusses the technological quality requirements to ensure the desired quality for stereotactic radiotherapy using photon external beam radiotherapy as defined by the DEGRO Working Group Radiosurgery and Stereotactic Radiotherapy and the DGMP Working Group for Physics and Technology in Stereotactic Radiotherapy. The covered aspects of this review are 1) imaging for target volume definition, 2) patient positioning and target volume localization, 3) motion management, 4) collimation of the irradiation and beam directions, 5) dose calculation, 6) treatment unit accuracy, and 7) dedicated quality assurance measures. For each part, an expert review for current state-of-the-art techniques and their particular technological quality requirement to reach the necessary accuracy for stereotactic radiotherapy divided into intracranial stereotactic radiosurgery in one single fraction (SRS), intracranial fractionated stereotactic radiotherapy (FSRT), and extracranial stereotactic body radiotherapy (SBRT) is presented. All recommendations and suggestions for all mentioned aspects of stereotactic radiotherapy are formulated and related uncertainties and potential sources of error discussed. Additionally, further research and development needs in terms of insufficient data and unsolved problems for stereotactic radiotherapy are identified, which will serve as a basis for the future assignments of the DGMP Working Group for Physics and Technology in Stereotactic Radiotherapy. The review was group peer-reviewed, and consensus was obtained through multiple working group meetings.

/pdf/technological-quality-requirements-for-stereotactic-2oz594nbu1.pdf

Technological quality requirements for stereotactic radiotherapy : Expert review group consensus from the DGMP Working Group for Physics and Technology in Stereotactic Radiotherapy

Importance of the field: Ionizing radiation (IR) can produce deleterious effects in living tissues, leading to significant morbidity and a potentially fatal illness affecting various organs dose-dependently. As people may be exposed to IR during cancer radiotherapy or as a result of a radiological/nuclear incident or act of terrorism, the danger of irradiation represents a serious public health problem. At present, however, this problem remains largely impervious to medical management. There is, therefore, a pressing need to develop safe and effective radiation countermeasure (RC) agents to prevent, mitigate or treat the harmful consequences of IR exposure.Areas covered in this review: Recent advances in the search for RC agents as reflected by the relevant patent literature of the past five years along with peer-reviewed publications are surveyed.What the reader will gain: A total of 43 patents, describing ∼ 38 chemically diverse compounds with RC potential are analyzed. These include antioxidants capabl...

Radiation countermeasure agents: an update.

Hypo-fractionated stereotactic radiotherapy (HSRT) is emerging as a valid treatment option for patients with single, large brain metastases (BMs). We analyzed a set of our patients treated with HSRT. The aim of this study was to evaluate local control (LC), brain distant progression (BDP), toxicity and overall survival (OS). From July 2011 to May 2015, 102 patients underwent HSRT consisting of 27Gy/3fractions for lesions 2.1–3 cm and 32Gy/4 fractions for lesions 3.1–5 cm. Local progression was defined as increase of the enhancing abnormality on MRI, and distant progression as new brain metastases outside the irradiated volume. Toxicity in terms of radio-necrosis was assessed using contrast enhanced T1MRI, T2 weighted-MRI and perfusion- MRI. The median maximum diameter of BM was 2.9 cm (range 2.1–5 cm), the median gross target volume (GTV) was 16.3 cm3 and the median planning target volume (PTV) was 33.7 cm3 The median,1,2-year local control rate was 30 months, 96, 96 %; the median, 1–2-year rate of BDP was 24 months, 12, 24 %; the median,1,2-year OS was 14 months, 69, 33 %. KPS and controlled extracranial disease were associated with significant survival benefit (p <0.01). Brain radio-necrosis occurred in six patients (5.8 %). In patients with single, large BMs unsuitable for surgical resection, HSRT is a safe and feasible treatment, with good brain local control and limited toxicity.

/pdf/hypo-fractionated-stereotactic-radiotherapy-alone-using-4xftnyicsq.pdf

Hypo-fractionated stereotactic radiotherapy alone using volumetric modulated arc therapy for patients with single, large brain metastases unsuitable for surgical resection.

Radiation therapy (RT) is commonly used for the treatment of localized prostate cancer (PCa). However, cancer cells often develop resistance to radiation through unknown mechanisms and pose an intractable challenge. Radiation resistance is highly unpredictable, rendering the treatment less effective in many patients and frequently causing metastasis and cancer recurrence. Understanding the molecular events that cause radioresistance in PCa will enable us to develop adjuvant treatments for enhancing the efficacy of RT. Radioresistant PCa depends on the elevated DNA repair system and the intracellular levels of reactive oxygen species (ROS) to proliferate, self-renew, and scavenge anti-cancer regimens, whereas the elevated heat shock protein 90 (HSP90) and the epithelial-mesenchymal transition (EMT) enable radioresistant PCa cells to metastasize after exposure to radiation. The up-regulation of the DNA repairing system, ROS, HSP90, and EMT effectors has been studied extensively, but not targeted by adjuvant therapy of radioresistant PCa. Here, we emphasize the effects of ionizing radiation and the mechanisms driving the emergence of radioresistant PCa. We also address the markers of radioresistance, the gene signatures for the predictive response to radiotherapy, and novel therapeutic platforms for targeting radioresistant PCa. This review provides significant insights into enhancing the current knowledge and the understanding toward optimization of these markers for the treatment of radioresistant PCa.

/pdf/profiles-of-radioresistance-mechanisms-in-prostate-cancer-uc2oo85gq9.pdf

Profiles of Radioresistance Mechanisms in Prostate Cancer.

A recombinant MnSOD is radioprotective for normal cells and radiosensitizing for tumor cells

A multichannel time-resolved system for medical optical tomography has been developed. Its main components are an eight channel single-photon counting detector and an ultrafast picosecond solid state laser. Several instrumental aspects concerning the optical coupling between the MCP-PMT and the optical fiber bundles, the electronic components and the roto-translation stages control have been examined. Moreover the accuracy limits in the determination of optical properties of phantom objects have been largely investigated taking into account the role played by the theoretical description of light propagation, the instrumental response function (by means of a convolution procedure) and the fitting algorithm. Information on image quality parameters (spatial resolution, contrast and SNR) have been also obtained by measuring Edge Response Function in different experimental conditions. In such a work, aqueous Intralipid solutions have been used as phantom objects. Furthermore, experimental investigations on well controlled inhomogeneous with different optical properties embedded in Intralipid solutions have been carried on. As last step of the work, preliminary imaging of cylindrical objects has been performed and a Linux version of TOAST code has been used in the imaging reconstruction.

Development of a time-domain tomographic system for optical imaging

Well-characterized phantom objects are necessary for investigating the performances of optical imaging systems based on time-resolved transmittance and fluorescence. For this purposes we have prepared inhomogeneous phantoms made of gelatinous objects placed in aqueous solutions of 10% Intralipid with different concentrations. The gelatinous objects have been prepared using a mixture of 10% Intralipid with agar at which absorbing ink have been added for transmittance based optical imaging system. For fluorescence measurements proper fluorescent dyes (rhodamine6G and IR125) have been added. Conventional optical characterization by spectrophotometric and spectrofluorimetric measurements have been performed. In addition, time-resolved transmittance and fluorescence measurements have been carried out. In particular, time-correlated single photon counting system has been used for time-resolved transmittance measurements. For time-resolved fluorescence measurements an optical imaging system based on a Ti:Sa laser and streak camera has been employed.

Preparation and characterization of phantom objects for optical imaging by time-resolved transmittance and fluorescence

Multicentre treatment planning inter-comparison in a national context: The liver stereotactic ablative radiotherapy case

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A recombinant MnSOD is radioprotective for normal cells and radiosensitizing for tumor cells

Development of a time-domain tomographic system for optical imaging

Preparation and characterization of phantom objects for optical imaging by time-resolved transmittance and fluorescence

Multicentre treatment planning inter-comparison in a national context: The liver stereotactic ablative radiotherapy case