Redox-Mediated and Ionizing-Radiation-Induced Inflammatory Mediators in Prostate Cancer Development and Treatment

SIGNIFICANCE: Radiation therapy is widely used for treatment of prostate cancer. Radiation can directly damage biologically important molecules; however, most effects of radiation-mediated cell killing are derived from the generated free radicals that alter cellular redox status. Multiple proinflammatory mediators can also influence redox status in irradiated cells and the surrounding microenvironment, thereby affecting prostate cancer progression and radiotherapy efficiency. RECENT ADVANCES: Ionizing radiation (IR)-generated oxidative stress can regulate and be regulated by the production of proinflammatory mediators. Depending on the type and stage of the prostate cancer cells, these proinflammatory mediators may lead to different biological consequences ranging from cell death to development of radioresistance. CRITICAL ISSUES: Tumors are heterogeneous and dynamic communication occurs between stromal and prostate cancer cells, and complicated redox-regulated mechanisms exist in the tumor microenvironment. Thus, antioxidant and anti-inflammatory strategies should be carefully evaluated for each patient at different stages of the disease to maximize therapeutic benefits while minimizing unintended side effects. FUTURE DIRECTIONS: Compared with normal cells, tumor cells are usually under higher oxidative stress and secrete more proinflammatory mediators. Thus, redox status is often less adaptive in tumor cells than in their normal counterparts. This difference can be exploited in a search for new cancer therapeutics and treatment regimes that selectively activate cell death pathways in tumor cells with minimal unintended consequences in terms of chemo- and radio-resistance in tumor cells and toxicity in normal tissues

Redox-Modulated Phenomena and Radiation Therapy: The Central Role of Superoxide Dismutases

SIGNIFICANCE: Ionizing radiation is a vital component in the oncologist\u27s arsenal for the treatment of cancer. Approximately 50% of all cancer patients will receive some form of radiation therapy as part of their treatment regimen. DNA is considered the major cellular target of ionizing radiation and can be damaged directly by radiation or indirectly through reactive oxygen species (ROS) formed from the radiolysis of water, enzyme-mediated ROS production, and ROS resulting from altered aerobic metabolism. RECENT ADVANCES: ROS are produced as a byproduct of oxygen metabolism, and superoxide dismutases (SODs) are the chief scavengers. ROS contribute to the radioresponsiveness of normal and tumor tissues, and SODs modulate the radioresponsiveness of tissues, thus affecting the efficacy of radiotherapy. CRITICAL ISSUES: Despite its prevalent use, radiation therapy suffers from certain limitations that diminish its effectiveness, including tumor hypoxia and normal tissue damage. Oxygen is important for the stabilization of radiation-induced DNA damage, and tumor hypoxia dramatically decreases radiation efficacy. Therefore, auxiliary therapies are needed to increase the effectiveness of radiation therapy against tumor tissues while minimizing normal tissue injury. FUTURE DIRECTIONS: Because of the importance of ROS in the response of normal and cancer tissues to ionizing radiation, methods that differentially modulate the ROS scavenging ability of cells may prove to be an important method to increase the radiation response in cancer tissues and simultaneously mitigate the damaging effects of ionizing radiation on normal tissues. Altering the expression or activity of SODs may prove valuable in maximizing the overall effectiveness of ionizing radiation

A combinatorial approach to the set-theoretic solutions of the Yang-Baxter equation

A bijective map $r: X^2 \longrightarrow X^2$, where $X = \{x_1, ..., x_n \}$ is a finite set, is called a \emph{set-theoretic solution of the Yang-Baxter equation} (YBE) if the braid relation $r_{12}r_{23}r_{12} = r_{23}r_{12}r_{23}$ holds in $X^3.$ A non-degenerate involutive solution $(X,r)$ satisfying $r(xx)=xx$, for all $x \in X$, is called \emph{square-free solution}. There exist close relations between the square-free set-theoretic solutions of YBE, the semigroups of I-type, the semigroups of skew polynomial type, and the Bieberbach groups, as it was first shown in a joint paper with Michel Van den Bergh. In this paper we continue the study of square-free solutions $(X,r)$ and the associated Yang-Baxter algebraic structures -- the semigroup $S(X,r)$, the group $G(X,r)$ and the $k$- algebra $A(k, X,r)$ over a field $k$, generated by $X$ and with quadratic defining relations naturally arising and uniquely determined by $r$. We study the properties of the associated Yang-Baxter structures and prove a conjecture of the present author that the three notions: a square-free solution of (set-theoretic) YBE, a semigroup of I type, and a semigroup of skew-polynomial type, are equivalent. This implies that the Yang-Baxter algebra $A(k, X,r)$ is Poincar\'{e}-Birkhoff-Witt type algebra, with respect to some appropriate ordering of $X$. We conjecture that every square-free solution of YBE is retractable, in the sense of Etingof-Schedler.Comment: 34 page

Gauss-Bonnet-Chern theorem on moduli space

In this paper, we proved the Gauss-Bonnet-Chern theorem on moduli space of polarized Kahler manifolds. Using our results, we proved the rationality of the Chern-Weil forms (with respect to the Weil-Petersson metric) on CY moduli. As an application in physics, by the Ashok-Douglas theory, counting the number of flux compactifications of the type IIb string on a Calabi-Yau threefold is related to the integrations of various Chern-Weil forms. We proved that all these integrals are finite (and also rational).Comment: Final version, Journal ref adde

A rapid and sensitive method for measuring cell adhesion

We have adapted the CyQuant® assay to provide a simple, rapid, sensitive and highly reproducible method for measuring cell adhesion. The modified CyQuant® assay eliminates the requirement for labour intensive fluorescent labelling protocols prior to experimentation and has the sensitivity to measure small numbers (>1000) of adherent cells

The potential of new tumor endothelium-specific markers for the development of antivascular therapy.

Angiogenesis is a hallmark of solid tumors, and disruption of tumor vasculature is an active anticancer therapy in some cases. Several proteins expressed on the surface of tumor endothelium have been identified during the last decade. However, due to the expression in both physiological and tumor angiogenesis, only a few targets have been developed for clinical therapeutics. By thorough SAGE analysis of mouse endothelial cells isolated from various normal resting tissues, regenerating liver, and liver-metastasized tumor, Seaman and colleagues in this issue of Cancer Cell have demonstrated organ-specific endothelial markers, physiological angiogenesis endothelial markers, and tumor endothelial markers and revealed striking differences between physiological and pathological angiogenesis

Analysis of the interfacial stresses of the strengthened rc beams externally bonded with cfrp sheet or steel plate

2002-2003 > Academic research: refereed > Publication in refereed journalVersion of RecordPublishe

Validation of nonlinear PCA

Linear principal component analysis (PCA) can be extended to a nonlinear PCA by using artificial neural networks. But the benefit of curved components requires a careful control of the model complexity. Moreover, standard techniques for model selection, including cross-validation and more generally the use of an independent test set, fail when applied to nonlinear PCA because of its inherent unsupervised characteristics. This paper presents a new approach for validating the complexity of nonlinear PCA models by using the error in missing data estimation as a criterion for model selection. It is motivated by the idea that only the model of optimal complexity is able to predict missing values with the highest accuracy. While standard test set validation usually favours over-fitted nonlinear PCA models, the proposed model validation approach correctly selects the optimal model complexity.Comment: 12 pages, 5 figure

Steam reforming on transition-metal carbides from density-functional theory

A screening study of the steam reforming reaction (CH_4 + H_2O -> CO + 3H_2) on early transition-metal carbides (TMC's) is performed by means of density-functional theory calculations. The set of considered surfaces includes the alpha-Mo_2C(100) surfaces, the low-index (111) and (100) surfaces of TiC, VC, and delta-MoC, and the oxygenated alpha-Mo_2C(100) and TMC(111) surfaces. It is found that carbides provide a wide spectrum of reactivities towards the steam reforming reaction, from too reactive via suitable to too inert. The reactivity is discussed in terms of the electronic structure of the clean surfaces. Two surfaces, the delta-MoC(100) and the oxygen passivated alpha-Mo_2C(100) surfaces, are identified as promising steam reforming catalysts. These findings suggest that carbides provide a playground for reactivity tuning, comparable to the one for pure metals.Comment: 6 pages, 4 figure