Citations

We report the results of a phase 2 trial using lenalidomide plus dexamethasone (Rev/Dex) as initial therapy for myeloma. Thirtyfour patients were enrolled. Lenalidomide was given orally 25 mg daily on days 1 to 21 of a 28-day cycle. Dexamethasone was given orally 40 mg daily on days 1 to 4, 9 to 12, and 17 to 20 of each cycle. Objective response was defined as a decrease in serum monoclonal protein level by 50% or greater and a decrease in urine M protein level by at least 90% or to a level less than 200 mg/24 hours, confirmed by 2 consecutive determinations at least 4 weeks apart. Thirty-one of 34 patients achieved an objective response, including 2 (6%) achieving complete response (CR) and 11 (32%) meeting criteria for both very good partial response and near complete response, resulting in an overall objective response rate of 91%. Of the 3 remaining patients not achieving an objective response, 2 had minor response (MR) and one had stable disease. Fortyseven percent of patients experienced grade III or higher nonhematologic toxicity, most commonly fatigue (15%), muscle weakness (6%), anxiety (6%), pneumonitis (6%), and rash (6%). Rev/Dex is a highly active regimen with manageable side effects in the treatment of newly diagnosed myeloma.

Purpose Monoclonal gammopathy of undetermined significance (MGUS) progresses to multiple myeloma or another related plasma cell disorder (PCD) at a rate of approximately 1% per year. Identification of patients with MGUS at high risk of progression will allow development of preventive strategies. We studied the prognostic value of circulating plasma cells (PCs) in patients with MGUS to predict progression. Patients and Methods Patients were eligible for this retrospective analysis if they were seen at the Mayo Clinic between 1984 and 1997, were diagnosed with MGUS, and had an analysis of the peripheral blood for circulating PCs by the slide-based immunofluorescence method. Patients were observed for progression to another PCD. Results Three hundred twenty-five patients were eligible and 63 (19%) had circulating PCs. Patients with circulating PCs were twice as likely (hazard ratio, 2.1) to experience progression to another PCD (most commonly myeloma), compared with those without circulating PCs (95% CI, 1.1 to 4.3; P = .03). In patients with circulating PCs, the median progression-free survival was 138 months compared with a median not yet reached for those without circulating PCs (P = .028). The median overall survival also was shorter for those with circulating PCs. Other factors with prognostic value were high levels of M protein and non–immunoglobulin G heavy-chain type. Conclusion The presence of circulating PCs, especially when combined with other known prognostic factors such as M protein concentration and immunoglobulin isotype, identify a group of individuals with MGUS at higher risk of progression to overt multiple myeloma.

Abstract Rationale Phenotypic and genotypic heterogeneity of lung cancer likely precludes the identification of a single predictive marker and suggests the importance of identifying and measuring multiple markers. Objectives We describe the use of a fluorescent protein microarray to identify and measure multiple non–small cell lung cancer–associated antibodies and show how simultaneous measurements can be combined into a single diagnostic assay. Methods T7 phage cDNA libraries of non–small cell lung cancer were first biopanned with plasma samples from normal subjects and patients with non–small cell lung cancer to enrich the component of tumor-associated proteins, and then applied to microarray slides. Two hundred twelve immunogenic phage-expressed proteins were identified from roughly 4,000 clones, using high-throughput screening with patient plasmas and assayed with 40 cancer and 41 normal plasma samples. Twenty patient and 21 normal plasma samples were randomly chosen and used for statistical determination of the predictive value of each putative marker. Statistical analysis identified antibody reactivity to seven unique phage-expressed proteins that were significantly different (p < 0.01) between patient and normal groups. The remaining 20 patient and 20 normal plasma samples were used as an independent test of the predictive ability of the selected markers. Main Results Measurements of the 5 most predictive phage proteins were combined in a logistic regression model that achieved 90% sensitivity and 95% specificity in prediction of patient samples, whereas leave-one-out statistical analysis achieved 88.9% diagnostic accuracy among all 81 samples. Conclusion Our data indicate that antibody profiling is a promising approach that could achieve high diagnostic accuracy for non–small cell lung cancer.

The mammalian dynamin-like protein DLP1/Drp1 has been shown to mediate both mitochondrial and peroxisomal fission. In this study, we have examined whether hFis1, a mammalian homologue of yeast Fis1, which has been shown to participate in mitochondrial fission by an interaction with DLP1/Drp1, is also involved in peroxisomal growth and division. We show that hFis1 localizes to peroxisomes in addition to mitochondria. Through differential tagging and deletion experiments, we demonstrate that the transmembrane domain and the short C-terminal tail of hFis1 is both necessary and sufficient for its targeting to peroxisomes and mitochondria, whereas the N-terminal region is required for organelle fission. hFis1 promotes peroxisome division upon ectopic expression, whereas silencing of Fis1 by small interfering RNA inhibited fission and caused tubulation of peroxisomes. These findings provide the first evidence for a role of Fis1 in peroxisomal fission and suggest that the fission machinery of mitochondria and peroxisomes shares common components.

Background— Most studies that are the basis of recommended volume thresholds for percutaneous coronary interventions (PCIs) predate the routine use of stent placement. Methods and Results— Data from New York’s Percutaneous Coronary Interventions Reporting System in 1998 to 2000 (n=107 713) were used to examine the impact of annual hospital volume and annual operator volume on in-hospital mortality, same-day coronary artery bypass graft (CABG) surgery, and same-stay CABG surgery after adjustment for differences in patients’ severity of illness. For a hospital-volume threshold of 400, the odds ratios for low-volume hospitals versus high-volume hospitals were 1.98 (95% CI, 1.17, 3.35) for in-hospital mortality, 2.07 (95% CI, 1.36, 3.15) for same-day CABG surgery, and 1.51 (95% CI, 1.03, 2.21) for same-stay CABG surgery. For an operator-volume threshold of 75, the odds ratios for low-volume versus high-volume operators were 1.65 (95% CI, 1.05, 2.60) for same-day CABG surgery and 1.55 (95% CI, 1.10, 2.18) for same-stay CABG surgery. Operator volume was not significantly associated with mortality. Also, for hospital volumes below 400 and operator volumes below 75, the respective odds of mortality, same-day CABG surgery, and same-stay CABG surgery were 5.92, 4.02, and 3.92 times the odds for hospital volumes of 400 or higher and operator volumes of 75 or higher. Conclusions— Higher-volume operators and hospitals continue to experience lower risk-adjusted PCI outcome rates.