Early reperfusion and late clinical outcomes in patients presenting with acute myocardial infarction randomly assigned to primary percutaneous coronary intervention or streptokinase

Primary percutaneous coronary intervention (PCI) has become an alternative to thrombolytic therapy as a reperfusion strategy for ST-elevation acute myocardial infarction (AMI). The main goal of this study was to determine whether PCI and thrombolytic therapy achieve comparable reperfusion rates, as evidenced by ST-segment resolution. Secondary end points included infarct vessel patency rates before hospital discharge and short- and long-term outcomes. Patients with ischemic chest pain with duration ≤12 hours and no contraindication for thrombolytic therapy were included. Between October 1993 and August 1995, 58 patients were randomly assigned to streptokinase (SK) and 54 patients to primary PCI. Baseline clinical characteristics and infarct location were well balanced in both groups. Median age (interquartile range) was 68 (58, 75) years, 29% were women, and 78% of the patients met at least one criterion for “not low risk” AMI (anterior location, age >70 years old, previous MI, systolic blood pressure 100 bpm). The median time from symptom onset to random assignment was 217 (139, 335) minutes in the PCI group and 210 (145, 334) minutes in the SK group. Median random assignment to balloon time was 82 (55, 100) minutes, and median random assignment to needle time was 15 (10, 26) minutes ( P < .0001). TIMI grade 3 flow after primary PCI was obtained in 85% of patients. The proportion of patients with ST-segment resolution ≥50% at 120 minutes was 80% in the PCI group and 50% in the SK group ( P = .001). The predischarge angiogram showed the presence of TIMI 3 flow in 96% of patients who received PCI and 65% of patients who received SK ( P < .001). A composite of in-hospital death, reinfarction, severe heart failure, stroke, and major bleeding occurred in 15% of patients who received PCI and 21% of patients who received SK ( P = .4). At 3 years, freedom from the composite end point of AMI, postdischarge revascularization, and death was 61% in the PCI group and 40% in the SK group ( P = .025). Our study shows that primary PCI, as compared with SK, is associated with more effective ST-segment resolution, higher patency rates in the infarct vessel at 7 days, and more favorable clinical outcomes at 3 years of follow-up

Proteogenomic Landscape of Breast Cancer Tumorigenesis and Targeted Therapy

© 2020 The Authors The integration of mass spectrometry-based proteomics with next-generation DNA and RNA sequencing profiles tumors more comprehensively. Here this “proteogenomics” approach was applied to 122 treatment-naive primary breast cancers accrued to preserve post-translational modifications, including protein phosphorylation and acetylation. Proteogenomics challenged standard breast cancer diagnoses, provided detailed analysis of the ERBB2 amplicon, defined tumor subsets that could benefit from immune checkpoint therapy, and allowed more accurate assessment of Rb status for prediction of CDK4/6 inhibitor responsiveness. Phosphoproteomics profiles uncovered novel associations between tumor suppressor loss and targetable kinases. Acetylproteome analysis highlighted acetylation on key nuclear proteins involved in the DNA damage response and revealed cross-talk between cytoplasmic and mitochondrial acetylation and metabolism. Our results underscore the potential of proteogenomics for clinical investigation of breast cancer through more accurate annotation of targetable pathways and biological features of this remarkably heterogeneous malignancy

Integrated Proteogenomic Characterization of Human High-Grade Serous Ovarian Cancer

To provide a detailed analysis of the molecular components and underlying mechanisms associated with ovarian cancer, we performed a comprehensive mass-spectrometry-based proteomic characterization of 174 ovarian tumors previously analyzed by The Cancer Genome Atlas (TCGA), of which 169 were high-grade serous carcinomas (HGSCs). Integrating our proteomic measurements with the genomic data yielded a number of insights into disease, such as how different copy-number alternations influence the proteome, the proteins associated with chromosomal instability, the sets of signaling pathways that diverse genome rearrangements converge on, and the ones most associated with short overall survival. Specific protein acetylations associated with homologous recombination deficiency suggest a potential means for stratifying patients for therapy. In addition to providing a valuable resource, these findings provide a view of how the somatic genome drives the cancer proteome and associations between protein and post-translational modification levels and clinical outcomes in HGSC. VIDEO ABSTRACT