Exploring Ovarian Cancer Cell Resistance to Rhenium Anticancer Complexes

Rhenium tricarbonyl complexes have been recently investigated as novel anticancer agents. However, little is understood about their mechanisms of action, as well as the means by which cancer cells respond to chronic exposure to these compounds. To gain a deeper mechanistic insight into these rhenium anticancer agents, we developed and characterized an ovarian cancer cell line that is resistant to a previously studied compound [Re(CO)₃(dmphen)(ptolICN)]⁺, where dmphen=2,9‐dimethyl‐1,10‐phenanthroline and ptolICN=para‐tolyl isonitrile, called TRIP. This TRIP‐resistant ovarian cancer cell line, A2780TR, was found to be 9 times less sensitive to TRIP compared to the wild‐type A2780 ovarian cancer cell line. Furthermore, the cytotoxicities of established drugs and other rhenium anticancer agents in the TRIP‐resistant cell line were determined. Notably, the drug taxol was found to exhibit a 184‐fold decrease in activity in the A2780TR cell line, suggesting that mechanisms of resistance towards TRIP and this drug are similar. Accordingly, expression levels of the ATP‐binding cassette transporter P‐glycoprotein, an efflux transporter known to detoxify taxol, were found to be elevated in the A2780TR cell line. Additionally, a gene expression analysis using the National Cancer Institute 60 cell line panel identified the MT1E gene to be overexpressed in cells that are less sensitive to TRIP. Because this gene encodes for metallothioneins, this result suggests that detoxification by this class of proteins is another mechanism for resistance to TRIP. The importance of this gene in the A2780TR cell line was assessed, confirming that its expression is elevated in this cell line as well. As the first study to investigate and identify the cancer cell resistance pathways in response to a rhenium complex, this report highlights important similarities and differences in the resistance responses of ovarian cancer cells to TRIP and conventional drugs.     

Gas‐phase rate coefficients for the reactions of O(3P), S(3P), Se(3P), and Te(3P) with alkenes: Application of perturbation frontier molecular orbital theory,correlations, and structure–activity relations (SARs)

The kinetics of the reactions of the atoms O(³P), S(³P), Se(³P), and Te(³P) with a series of alkenes are examined for correlations relating the logarithms of the rate coefficients to the energies of the highest occupied molecular orbitals (HOMOs) of the alkenes. These correlations may be employed to predict rate coefficients from the calculated HOMO energy of any other alkene of interest. The rate coefficients obtained from the correlations were used to © 2006 Wiley Periodicals, Inc. Int J Chem Kinet 38: 351–356, 2006     

Observations on the detection of b‐ and y‐type ions in the collisionally activated decomposition spectra of protonated peptides

Tandem mass spectrometric data from peptides are routinely used in an unsupervised manner to infer product ion sequence and hence the identity of their parent protein. However, significant variability in relative signal intensity of product ions within peptide tandem mass spectra is commonly observed. Furthermore, instrument‐specific patterns of fragmentation are observed, even where a common mechanism of ion heating is responsible for generation of the product ions. This information is currently not fully exploited within database searching strategies; this motivated the present study to examine a large dataset of tandem mass spectra derived from multiple instrumental platforms. Here, we report marked global differences in the product ion spectra of protonated tryptic peptides generated from two of the most common proteomic platforms, namely tandem quadrupole‐time‐of‐flight and quadrupole ion trap instruments. Specifically, quadrupole‐time‐of‐flight tandem mass spectra show a significant under‐representation of N‐terminal b‐type fragments in comparison to quadrupole ion trap product ion spectra. Energy‐resolved mass spectrometry experiments conducted upon test tryptic peptides clarify this disparity; b‐type ions are significantly less stable than their y‐type N‐terminal counterparts, which contain strongly basic residues. Secondary fragmentation processes which occur within the tandem quadrupole‐time‐of‐flight device account for the observed differences, whereas this secondary product ion generation does not occur to a significant extent from resonant excitation performed within the quadrupole ion trap. We suggest that incorporation of this stability information in database searching strategies has the potential to significantly improve the veracity of peptide ion identifications as made by conventional database searching strategies. Copyright © 2009 John Wiley & Sons, Ltd.     

Assessment of compliance of analytical results with regulatory or specification limits

 In some cases the compliance of a measurement result with a limit value will be unclear and a 'judgment' is required based on agreed criteria. Recent developments in the estimation of measurement uncertainty have opened up the possibility of a more rational approach to such problems. This paper briefly reviews some of the issues and current practices and suggests a pragmatic way forward. Received: 26 August 1998 · Accepted: 31 August 1998     

A canonical structure theorem for finite joining-rank maps

A numerical isomorphism invariant,joining-rank, was introduced in [1] as a quantitative generalization of Rudolph’s property of minimal selfjoinings. Therein, a structure theory was developed for those transformationsT whose joining-rank, jr (T), is finite. Here, we sharpen the theorem and show it to be canonical: If jr (T)<∞ then there is a unique triple 〈e, p, S〉 wheree andp are natural numbers andS is a map with minimal self-joinings, such thatT is ane-point extension ofS ^P. Furthermore, the producte·p equals the joining-rank ofT. This theorem applies to any finite-rank mixing map, since for such maps the rank dominates the joining-rank. Another corollary is that any rank-1 transformation which is partial-mixing has minimal self-joinings. This partially answers a question of [3]. Partially supported by a National Science Foundation Postdoctoral Research Fellowship.     

On a deception game with three boxes

This paper clarifies the status of a deception game posed by Spencer. We show the value of this game is zero.