Peter R. Mueller

Bio: Peter R. Mueller is an academic researcher from Harvard University. The author has contributed to research in topics: Percutaneous & Biopsy. The author has an hindex of 97, co-authored 613 publications receiving 34457 citations. Previous affiliations of Peter R. Mueller include Northwestern University & National Institutes of Health.

Dicer, Drosha, and outcomes in patients with ovarian cancer

Abstract: BACKGROUND We studied Dicer and Drosha, components of the RNA-interference machinery, in ovarian cancer. METHODS We measured messenger RNA (mRNA) levels of Dicer and Drosha in specimens of invasive epithelial ovarian cancer from 111 patients, using a quantitative reverse-transcriptase-polymerase-chain-reaction assay, and compared the results with clinical outcomes. Validation was performed with the use of published microarray data from cohorts of patients with ovarian, breast, and lung cancer. Mutational analyses of genomic DNA from the Dicer and Drosha genes were performed in a subgroup of ovarian-cancer specimens. Dicer-dependent functional assays were performed by means of in vitro transfection with small interfering RNA (siRNA) and short hairpin RNA (shRNA). RESULTS Levels of Dicer and Drosha mRNA correlated with the levels of expression of the corresponding protein and were decreased in 60% and 51% of ovarian-cancer specimens, respectively. Low Dicer expression was significantly associated with advanced tumor stage (P=0.007), and low Drosha expression with suboptimal surgical cytoreduction (P=0.02). Cancer specimens with both high Dicer expression and high Drosha expression were associated with increased median survival (>11 years, vs. 2.66 years for other subgroups; P<0.001). We found three independent predictors of reduced disease-specific survival in multivariate analyses: low Dicer expression (hazard ratio, 2.10; P=0.02), high-grade histologic features (hazard ratio, 2.46; P=0.03), and poor response to chemotherapy (hazard ratio, 3.95; P<0.001). Poor clinical outcomes among patients with low Dicer expression were validated in additional cohorts of patients. Rare missense mutations were found in the Dicer and Drosha genes, but their presence or absence did not correlate with the level of expression. Functional assays indicated that gene silencing with shRNA, but not siRNA, may be impaired in cells with low Dicer expression. CONCLUSIONS Our findings indicate that levels of Dicer and Drosha mRNA in ovarian-cancer cells have associations with outcomes in patients with ovarian cancer.

Percutaneous US-guided radio-frequency tissue ablation of liver metastases: treatment and follow-up in 16 patients.

Abstract: PURPOSE: To determine the potential efficacy of radio-frequency (RF) ablation of liver metastases during long-term follow-up. MATERIALS AND METHODS: Sixteen patients with 31 hepatic metastases were treated with percutaneous, ultrasound-guided RF ablation. RF was applied to monopolar electrodes (2-3-cm tip exposure) either individually or within a multiprobe array (two to four probes) for 6 minutes at 90 degrees C over one to four treatment sessions per metastasis. RESULTS: In only one of 75 sessions, a moderate complication, self-limited intraperitoneal hemorrhage, was observed. Four patients (four lesions) underwent surgical resection 15-60 days after RF treatment. Residual, viable tumor was seen in all of these patients. The remaining 12 patients were followed up for 9-29 months (mean, 18.1 months). In these patients, 18 of 27 lesions remained stable or decreased in size and showed no enhancement at computed tomography and/or magnetic resonance imaging for at least 9 months. Two patients died of dissemi...

Cystic tumors of the pancreas. New clinical, radiologic, and pathologic observations in 67 patients

Abstract: Within a 12-year period we treated 67 patients (49 women, 18 men; mean age, 61 years) with cystic neoplasms of the pancreas, including 18 serous cystic adenomas, 15 benign mucinous cystic neoplasms, 27 mucinous cystadenocarcinomas, 3 papillary cystic tumors, 2 cystic islet cell tumors, and 2 cases of mucinous ductal ectasia. Mean tumor size was 6 cm (2 to 16 cm). In 39% the patients had no symptoms, and in 37% the lesions had been misdiagnosed as a pseudocyst. Computed tomography was useful for detection, for distinguishing the microcystic subgroup of serous cystadenoma, and for showing rim calcification (all 7 cases were malignant) but was not reliable for distinguishing neoplasm from pseudocyst, serous from mucinous tumors, or benign from malignant. Arteriography showed hypervascularity in 4 of 10 serous adenomas, 3 of 11 mucinous carcinomas, and 1 of 1 papillary cystic tumors. Endoscopic pancreatography showed no communication with the cyst cavity in 37 of 37 cases of cystic neoplasms but opacified the ectatic ducts in 2 of 2 cases of mucinous ductal ectasia. Stenosis or obstruction of the pancreatic duct indicated cancer. The tumor was resected by distal pancreatectomy in 25 patients, by proximal resection in 29, and by total pancreatectomy in one, with no operative deaths. Forty-four per cent of the tumors were malignant. In 10 cases the tumor was unresectable because of local extension or distant metastases, and those patients died at a mean of 4 months. Seventy-five per cent of those resected for cure are alive without evident recurrence. Because the epithelial lining of the tumor was partially (5% to 98%) absent in 40% to 72% of cases of the major tumor types, and the mucinous component comprised only about 65% of mucinous cystadenoma lining, misdiagnoses on frozen and even permanent sections were made. Mitoses and histologic solid growth correlated with malignancy. Neuroendocrine elements were seen in 87% of benign and 47% of malignant mucinous tumors. It is recommended that the terms macrocystic and microcystic be abandoned in favor of the histologic designations serous and mucinous. Incomplete examination of the cyst wall can be misleading, however. It is suggested that mucinous ductal ectasia be recognized separately from cystic tumors and that all of these lesions be resected, with the possible exception of asymptomatic confirmed serous cystadenomas.

ACC/AHA 2005 Practice Guidelines for the Management of Patients With Peripheral Arterial Disease (Lower Extremity, Renal, Mesenteric, and Abdominal Aortic)

Abstract: Patients With Peripheral Arterial Disease (Lower Extremity, Renal, Mesenteric, and Abdominal Aortic) A Collaborative Report from the American Association for Vascular Surgery/Society for Vascular Surgery,* Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, Society of Interventional Radiology, and the ACC/AHA Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Peripheral Arterial Disease) Endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation; National Heart, Lung, and Blood Institute; Society for Vascular Nursing; TransAtlantic Inter-Society Consensus; and Vascular Disease Foundation

MicroRNA therapeutics: towards a new era for the management of cancer and other diseases

Abstract: MicroRNAs (miRNAs) are small non-coding RNAs that can modulate mRNA expression. Insights into the roles of miRNAs in development and disease have led to the development of new therapeutic approaches that are based on miRNA mimics or agents that inhibit their functions (antimiRs), and the first such approaches have entered the clinic. This Review discusses the role of different miRNAs in cancer and other diseases, and provides an overview of current miRNA therapeutics in the clinic. In just over two decades since the discovery of the first microRNA (miRNA), the field of miRNA biology has expanded considerably. Insights into the roles of miRNAs in development and disease, particularly in cancer, have made miRNAs attractive tools and targets for novel therapeutic approaches. Functional studies have confirmed that miRNA dysregulation is causal in many cases of cancer, with miRNAs acting as tumour suppressors or oncogenes (oncomiRs), and miRNA mimics and molecules targeted at miRNAs (antimiRs) have shown promise in preclinical development. Several miRNA-targeted therapeutics have reached clinical development, including a mimic of the tumour suppressor miRNA miR-34, which reached phase I clinical trials for treating cancer, and antimiRs targeted at miR-122, which reached phase II trials for treating hepatitis. In this article, we describe recent advances in our understanding of miRNAs in cancer and in other diseases and provide an overview of current miRNA therapeutics in the clinic. We also discuss the challenge of identifying the most efficacious therapeutic candidates and provide a perspective on achieving safe and targeted delivery of miRNA therapeutics.

Optimal Versus Naive Diversification: How Inefficient is the 1/N Portfolio Strategy?

Abstract: We evaluate the out-of-sample performance of the sample-based mean-variance model, and its extensions designed to reduce estimation error, relative to the naive 1-N portfolio. Of the 14 models we evaluate across seven empirical datasets, none is consistently better than the 1-N rule in terms of Sharpe ratio, certainty-equivalent return, or turnover, which indicates that, out of sample, the gain from optimal diversification is more than offset by estimation error. Based on parameters calibrated to the US equity market, our analytical results and simulations show that the estimation window needed for the sample-based mean-variance strategy and its extensions to outperform the 1-N benchmark is around 3000 months for a portfolio with 25 assets and about 6000 months for a portfolio with 50 assets. This suggests that there are still many "miles to go" before the gains promised by optimal portfolio choice can actually be realized out of sample. The Author 2007. Published by Oxford University Press on behalf of The Society for Financial Studies. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org, Oxford University Press.