ABSTRACT
BACKGROUND: Bone marrow-derived endothelial progenitor cells (EPCs) are critical for metastatic progression. This study explores the effect of tetrathiomolybdate (TM), an anti-angiogenic copper chelator, on EPCs in patients at high risk for breast cancer recurrence. PATIENTS AND METHODS: This phase 2 study enrolled breast cancer patients with stage 3 and stage 4 without evidence of disease (NED), and stage 2 if triple-negative. TM 100 mg orally was administered to maintain ceruloplasmin <17 mg/dl for 2 years or until relapse. The primary end point was change in EPCs. RESULTS: Forty patients (28 stage 2/3, 12 stage 4 NED) were enrolled. Seventy-five percent patients achieved the copper depletion target by 1 month. Ninety-one percent of triple-negative patients copper-depleted compared with 41% luminal subtypes. In copper-depleted patients only, there was a significant reduction in EPCs/ml by 27 (P = 0.04). Six patients relapsed while on study, of which only one patient had EPCs maintained below baseline. The 10-month relapse-free survival was 85.0% (95% CI 74.6%-96.8%). Only grade 3/4 toxicity was hematologic: neutropenia (3.1% of cycles), febrile neutropenia (0.2%), and anemia (0.2%). CONCLUSIONS: TM is safe and appears to maintain EPCs below baseline in copper-depleted patients. TM may promote tumor dormancy and ultimately prevent relapse.
Subject(s)
Breast Neoplasms/blood , Copper/blood , Endothelial Cells/metabolism , Molybdenum/therapeutic use , Neoplasm Recurrence, Local/prevention & control , Stem Cells/metabolism , Adult , Aged , Breast Neoplasms/diagnosis , Breast Neoplasms/drug therapy , Chelating Agents/therapeutic use , Endothelial Cells/drug effects , Female , Humans , Middle Aged , Molybdenum/pharmacology , Neoplasm Recurrence, Local/blood , Risk Factors , Stem Cells/drug effectsABSTRACT
The eukaryotic RNA polymerases Pol I, Pol II, and Pol III are the central multiprotein machines that synthesize ribosomal, messenger, and transfer RNA, respectively. Here we provide a catalog of available structural information for these three enzymes. Most structural data have been accumulated for Pol II and its functional complexes. These studies have provided insights into many aspects of the transcription mechanism, including initiation at promoter DNA, elongation of the mRNA chain, tunability of the polymerase active site, which supports RNA synthesis and cleavage, and the response of Pol II to DNA lesions. Detailed structural studies of Pol I and Pol III were reported recently and showed that the active center region and core enzymes are similar to Pol II and that strong structural differences on the surfaces account for gene class-specific functions.
Subject(s)
DNA-Directed RNA Polymerases , Models, Chemical , Models, Genetic , RNA/biosynthesis , RNA/chemistry , Transcription, Genetic/genetics , Animals , DNA-Directed RNA Polymerases/chemistry , DNA-Directed RNA Polymerases/genetics , DNA-Directed RNA Polymerases/ultrastructure , Enzyme Activation , Humans , Models, Molecular , RNA/geneticsABSTRACT
PURPOSE: We analyzed the efficacy and side effects of a microprocessor controlled high frequency unit for transurethral resection of the prostate. MATERIALS AND METHODS: A high frequency device with microprocessor control was used in 934 consecutive patients undergoing transurethral resection of the prostate. Indications for transurethral resection, medical history, preoperative findings, operative parameters, operative and immediate postoperative complications, and postoperative peak flow rate and residual urine were evaluated. RESULTS: Postoperative peak flow rate and residual urine were comparable to those with standard transurethral resection of the prostate. One patient died on postoperative day 1 for a mortality rate of 0.1%. The immediate morbidity rate was 6.9%. CONCLUSIONS: Morbidity and mortality in this study were lower than those in previous series on transurethral resection of the prostate.
Subject(s)
Electrosurgery/instrumentation , Microcomputers , Prostatectomy/instrumentation , Prostatectomy/methods , Prostatic Diseases/surgery , Aged , Humans , Male , Middle Aged , Prostatic Diseases/physiopathology , UrinationABSTRACT
Two large (N = 1584 and N = 1330) population groups of workers exposed to asbestos as insulators (I) or sheet metal workers (SM) were compared. Prevalence rates of radiographic changes including pleural fibrosis (circumscribed and diffuse) were found to be much higher in I than SM. An integrative index of pleural fibrosis (INDEX) showed similar distribution patterns in the two groups; the effect of INDEX on FVC% predicted was more marked in insulators. Factors that could contribute to this difference are thought to be the higher prevalence of interstitial pulmonary fibrosis (probably including that which is not yet radiologically detectable) in I than in SM, the possibility of more extensive pleural fibrosis in areas not accessible to the standard chest X ray (and thus not affecting INDEX) and a higher proportion of diffuse pleural fibrosis in the I group.
