Evaluation of the radiosensitizing potency of chemotherapeutic agents in prostate cancer cells

PURPOSE: Despite recent advances in the treatment of metastatic prostate cancer, survival rates are low and treatment options are limited to chemotherapy and hormonal therapy. Although ionizing radiation is used to treat localized and metastatic prostate cancer, the most efficient use of radiotherapy is yet to be defined. Our purpose was to determine in vitro the potential benefit to be gained by combining radiation treatment with cytotoxic drugs. MATERIALS AND METHODS: Inhibitors of DNA repair and heat shock protein 90 and an inducer of oxidative stress were evaluated in combination with x-radiation for their capacity to reduce clonogenic survival and delay the growth of multicellular tumor spheroids. RESULTS: Inhibitors of the PARP DNA repair pathway, olaparib and rucaparib, and the HSP90 inhibitor 17-DMAG, enhanced the clonogenic cell kill and spheroid growth delay induced by x-radiation. However, the oxidative stress-inducing drug elesclomol failed to potentiate the effects of x-radiation. PARP inhibitors arrested cells in the G2/M phase when administered as single agents or in combination with radiation, whereas elesclomol and 17-DMAG did not affect radiation-induced cell cycle modulation. CONCLUSIONS: These results indicate that radiotherapy of prostate cancer may be optimized by combination with inhibitors of PARP or HSP90, but not elesclomol

Leading economic indexes for New York State and New Jersey

The authors develop indexes of leading economic indicators for New York State and New Jersey over the 1972-99 period. They find that the leading indexes convey useful information about the future course of economic activity in both states. The authors then construct separate indexes to forecast recessions and expansions in each state. The movements of the recession and expansion indexes are found to display a close relationship with the behavior of the leading indexes. Accordingly, the recession and expansion indexes allow the authors to extend the informational content of the leading indexes by estimating the probability of an upcoming cyclical change in state economic activity within the next nine months.Economic indicators ; New York (State) ; New Jersey ; Index numbers (Economics) ; Economic conditions - United States ; Federal Reserve District, 2nd

Unusual structure-energy correlations in intramolecular Diels–Alder reaction transition states

Detailed analysis of calculated data from an experimental/computational study of intramolecular furan Diels–Alder reactions has led to the unusual discovery that the mean contraction of the newly forming C-C σ-bonds from the transition state to the product shows a linear correlation with both reaction Gibbs free energies and reverse energy barriers. There is evidence for a similar correlation in other intramolecular Diels–Alder reactions involving non-aromatic dienes. No such correlation is found for intermolecular Diels–Alder reactions

Two new indexes offer a broad view of economic activity in the New York - New Jersey region

The authors develop two coincident indexes that provide a comprehensive measure of economic activity in New Jersey, New York State, and New York City.Federal Reserve District, 2nd ; Economic conditions - United States ; New York (N.Y.) ; New York (State) ; New Jersey ; Index numbers (Economics)

A Study of Majolica Pottery Decoration

It was the purpose of this study to investigate the origin and development of majolica decoration and to execute original variations of these techniques on pottery made by the candidate

Substitution effects in intramolecular furan cycloadditions

The intramolecular Diels-Alder reaction of furan (IMDAF) provides a high degree of structural complexity in one step. However, reaction reversibility issues and the lower reactivity of furan in comparison to non-aromatic dienes prevent more widespread use of furan as a diene component in such reactions. Initial efforts to develop a new mode of organocatalysis which we hoped would facilitate IMDAF reaction was unfortunately unsuccessful, thus alternative means of IMDAF facilitation were investigated. For the first time, a comprehensive synthetic and computational study of the effect of halogen substitution on the IMDAF reaction has been undertaken. We have successfully demonstrated that halogenation of the furan moiety facilitates the IMDAF reaction (displaying increased reactivity to the non-halogenated analogue, regardless of halogen position), whereas dienophile halogenation hinders it. Additionally, careful selection of the position of the halogen on the furan can somewhat overcome the detrimental effect of having a halogen on the dienophile leading to highly functionalised cycloadducts with potential for further modification. Computational data produced by Martin Paterson and Justyna McKinlay support the idea that frontier molecular orbital effects cannot explain the experimental observations and we thus believe that the reactions are controlled by the interplay of three factors: positive charge stabilisation in the transition state and product, steric effects and a dipolar interaction term identified by the high level calculations. Finally, we have briefly demonstrated that nitro groups on the furan moiety also facilitate the IMDAF reaction whereas acyl groups appear to hinder the reaction. STEREOCHEMICAL ABSTRACT Any chiral compounds included in this thesis are racemic in nature. However, for clarity, such mixtures are schematically represented by drawings of only one of the enantiomers.EPSR

Halogenation effects in Intramolecular Furan Diels-Alder reactions:broad scope synthetic and computational studies

For the first time a comprehensive synthetic and computational study of the effect of halogen substitution on both furan and dienophile for the intramolecular Furan Diels-Alder (IMDAF) reaction has been undertaken. Contrary to our initial expectations, halogen substitution on the dienophile was found to have a significant effect, making the reactions slower and less thermodynamically favourable. However, careful choice of the site of furan halogenation could be used to overcome dienophile halogen substitution, leading to highly functionalised cycloadducts. These reactions are thought to be controlled by the interplay of three factors: positive charge stabilisation in the transition state and product, steric effects and a dipolar interaction term identified by high level calculations. Frontier orbital effects do not appear to make a major contribution in determining the viability of these reactions, which is consistent with our analysis of calculated transition state structural data

Is the worst over? Economic indexes and the course of the recession in New York and New Jersey

The New York-New Jersey region entered a pronounced downturn in 2008, but the pace of decline eased considerably in spring 2009 and then leveled off in July, according to three key Federal Reserve Bank of New York economic indexes. These developments, in conjunction with a growing consensus that the national economy is headed for recovery, suggest that the worst may be over for the region's economy. However, a downsizing of the area's critical finance sector could pose a major risk to the economic outlook going forward--particularly for New York City.Federal Reserve Bank of New York ; Federal Reserve District, 2nd ; Economic conditions ; Economic indicators