Clinical Efficacy and Predictive Molecular Markers of Neoadjuvant Gemcitabine and Pemetrexed in Resectable Non-small Cell Lung Cancer

BackgroundA trial of neoadjuvant gemcitabine and pemetrexed (GP) chemotherapy in patients with resectable non-small cell lung cancer was conducted. The goal was to achieve a disease response rate of 50% and to determine if the expression levels of genes associated with GP metabolism are predictive of response.MethodsPatients had staging with a computed tomography scan, whole body F-18 fluorodeoxyglucose positron emission tomography, and mediastinoscopy. Four biweekly cycles of GP were given. Patients were restaged, and those with resectable stage IB-III disease had thoracotomy. Fresh frozen tumor specimens were collected before and after chemotherapy and the mRNA levels of 14 target genes determined by real-time reverse transcription polymerase chain reaction.ResultsFifty-two patients started therapy. The radiographic disease response rate was 35% (95% confidence interval 21.7-49.6%), and the progression rate was 6%. Forty-six patients had a thoracotomy. The complete tumor resection rate was 77% (40/52). There were no perioperative deaths or deaths related to chemotherapy. Tumor response to chemotherapy was inversely correlated with the level of expression of RRM1 (p < 0.001; regulatory subunit of ribonucleotide reductase) and TS (p = 0.006; thymidylate synthase); i.e., the reduction in tumor size was greater in those with low levels of expression.ConclusionsNeoadjuvant GP is well tolerated and produces an objective response rate of 35%. Tumoral RRM1 and TS mRNA levels are predictive of disease response and should be considered as parameters for treatment selection in future trials with this regimen

Sulfur isotope measurement of sulfate and sulfide by high-resolution MC-ICP-MS

Author Posting. © Elsevier B.V. , 2008. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Chemical Geology 253 (2008): 102-113, doi:10.1016/j.chemgeo.2008.04.017.We have developed a technique for the accurate and precise determination of 34S/32S isotope ratios (δ34S) in sulfur-bearing minerals using solution and laser ablation multiple-collector inductively coupled plasma mass spectrometry (MC-ICP-MS). We have examined and determined rigorous corrections for analytical difficulties such as instrumental mass bias, unresolved isobaric interferences, blanks, and laser ablation- and matrix-induced isotopic fractionation. Use of high resolution sector-field mass spectrometry removes major isobaric interferences from O2+. Standard–sample bracketing is used to correct for the instrumental mass bias of unknown samples. Blanks on sulfur masses arising from memory effects and residual oxygen-tailing are typically minor (< 0.2‰, within analytical error), and are mathematically removed by on-peak zero subtraction and by bracketing of samples with standards determined at the same signal intensity (within 20%). Matrix effects are significant (up to 0.7‰) for matrix compositions relevant to many natural sulfur-bearing minerals. For solution analysis, sulfur isotope compositions are best determined using purified (matrix-clean) sulfur standards and sample solutions using the chemical purification protocol we present. For in situ analysis, where the complex matrix cannot be removed prior to analysis, appropriately matrix-matching standards and samples removes matrix artifacts and yields sulfur isotope ratios consistent with conventional techniques using matrix-clean analytes. Our method enables solid samples to be calibrated against aqueous standards; a consideration that is important when certified, isotopically-homogeneous and appropriately matrix-matched solid standards do not exist. Further, bulk and in situ analyses can be performed interchangeably in a single analytical session because the instrumental setup is identical for both. We validated the robustness of our analytical method through multiple isotope analyses of a range of reference materials and have compared these with isotope ratios determined using independent techniques. Long-term reproducibility of S isotope compositions is typically 0.20‰ and 0.45‰ (2σ) for solution and laser analysis, respectively. Our method affords the opportunity to make accurate and relatively precise S isotope measurement for a wide range of sulfur-bearing materials, and is particularly appropriate for geologic samples with complex matrix and for which high-resolution in situ analysis is critical.Support was provided by National Science Foundations grants OCE-0327448 to P.R.C. and W.B. and OCE-0622982 to O.J.R. Support for L.A.B. was provided by the Woods Hole Oceanographic Institution Plasma Facility Development Grant (NSF-EAR/IF-0318137)

Antegrade versus Retrograde Cardioplegia for Uncomplicated Coronary Artery Disease: A Comparative Study

Since the introduction of the retrograde administration of cardioplegic solutions in cardiac surgery in the mid-1980's, the technique has been widely adopted for routine use in high risk patients with impaired ventricular function, based on favorable results demonstrated in clinical series. However, we sought to evaluate the benefits of routine use of this method in low risk patients by means of a retrospective review of 34 consecutive non-repeat, isolated coronary artery bypass grafting patients with left ventricular ejection fractions > 35%. Seventeen patients received intermittent ante grade cardioplegia exclusively and 17 received ante grade induction followed by intermittent retrograde cardioplegia maintenance. No significant baseline differences were found between the two groups. There were no deaths or major complications in either group. Retrograde cardioplegia patients had significantly lower pulmonary artery diastolic pressures in the first 24 hours postoperatively, accompanied by a non-significant trend toward higher cardiac indices during this same period. Phenylephrine infusions were used more frequently during the postoperative period in the retrograde group (p = 0.021). Fewer pulmonary complications were seen in the retrograde cardioplegia group (p=0.042), in addition to non-significant trends toward less atrial arrhythmias and less hospital days. No adverse effects or increased operative time could be attributed to the retrograde administration of cardioplegic solution in this study population. Based on the results from this small clinical series, retrograde cardioplegia administration offers distinct advantages for myocardial protection in low risk coronary bypass patients, as manifested by improved postoperative hemodynamic performance, with no significant adverse effects. A prospective, randomized trial of this technique in a larger, similar patient population is likely to show even more compelling positive results favoring the routine use of retrograde administration of cardioplegic solutions

by multi-angle

Automated classification and recognition of bacterial particles in flo