PPARgamma1 as a molecular target of eicosapentaenoic acid in human colon cancer (HT-29) cells.

Diets high in (n-3) PUFA decrease colon cancer development and suppress colon tumor growth, but the molecular mechanism through which these compounds act is largely unknown. We sought to determine whether PPARgamma1 serves as a molecular link between the physiological actions of eicosapentaenoic acid (EPA) in human colon cancer cells (HT-29). At nutritionally relevant concentrations, EPA stimulated a PPAR response element (PPRE) reporter assay in a dose-responsive manner in HT-29 cells.

The costs of nosocomial infections.

Background: Although nosocomial infections (NIs) are widely regarded as expensive complications of healthcare delivery, their costs have not been rigorously quantified in large-scale studies. Additionally, problems that can bias cost estimates have often gone unaddressed. For example, are NIs more likely to cause significant extra length of stay (LOS) and costs, or are they more likely to be relatively inexpensive and inevitable consequences of long and expensive hospitalizations? This study is the largest of its kind to provide a rigorous analysis of the costs of NIs.

PPARalpha ligands reduce PCB-induced endothelial activation: possible interactions in inflammation and atherosclerosis.

Exposure to polychlorinated biphenyls (PCBs) can activate inflammatory responses in vascular endothelial cells. Activation of peroxisome proliferator-activated receptors (PPARs) by nutrients or synthetic agonists has been shown to block pro-inflammatory responses both in vitro and in vivo. Here we demonstrate that activation of PPARalpha by synthetic agonists can reduce 3,3'4,4'-tetrachlorobiphenyl (PCB77)-induced endothelial cell activation.

MAZ drives tumor-specific expression of PPAR gamma 1 in breast cancer cells.

The peroxisome proliferator-activated receptor gamma 1 (PPARgamma1) is a nuclear receptor that plays a pivotal role in breast cancer and is highly over-expressed relative to normal epithelia. We have previously reported that the expression of PPARgamma1 is mediated by at least six distinct promoters and expression in breast cancer is driven by a tumor-specific promoter (pA1). Deletional analysis of this promoter fragment revealed that the GC-rich, 263 bp sequence proximal to the start of exon A1, is sufficient to drive expression in breast cancer cells but not in normal, human mammary epithelial cells (HMEC).

Drug costs and out-of-pocket spending in cancer clinical trials.

Objective: To estimate the effect of clinical trial participation on drug utilization, drug costs, and out-of-pocket expenditures for cancer patients.

Methods: The study used a national probability sample of patients participating in cancer clinical trials and a matched cohort of patients not enrolled in trials but receiving treatment for the same cancers from the same providers. Subjects were interviewed about prescription drug utilization and out-of-pocket drug expenditures.

Damages caps in medical malpractice cases.

This article reviews the empirical literature on the effects of damages caps and concludes that the better-designed studies show that damages caps reduce liability insurance premiums. The effects of damages caps on defensive medicine, physicians' location decisions, and the cost of health care to consumers are less clear. The only study of whether consumers benefit from lower health insurance premiums as a result of damages caps found no impact.

Cost-utility analysis of emergency department thoracotomy for trauma victims.

Background: Our objective was to assess the cost-effectiveness of emergency department thoracotomy (EDT) performed on both penetrating and blunt trauma victims, using both published survival and outcome data and previously unaccounted for data on the cost of occupational exposure.

Methods: Cost-utility analysis was performed using decision-analytic models constructed for both penetrating and blunt trauma scenarios. Survival and impairment data, the rates and costs of occupational exposure, and the utilities of neurologic impairment and provider seroconversion were all based on published literature.

Transactivation of ERalpha by Rosiglitazone induces proliferation in breast cancer cells.

In the present study, we demonstrate that Rosiglitazone (Rosi), a thiazolidinedione and PPARgamma agonist, induces ERE (Estrogen Receptor Response Element) reporter activity, pS2 (an endogenous ER gene target) expression, and proliferation of ER positive breast cancer (MCF-7) cells. By performing a dose-response assay, we determined that high concentrations of Rosi inhibit proliferation, while low concentrations of Rosi induce proliferation. Using the anti-estrogen ICI, ER negative breast cancer (MDA-MB-231) cells, and a prostate cancer cell line (22Rv1) deficient in both ERalpha and PPARgamma, we determined that Rosiglitazone-induced ERE reporter activation and proliferation is through an ERalpha dependent mechanism.

Tort law and medical malpractice insurance premiums.

This paper estimated the effects of tort law and insurer investment returns on physician malpractice insurance premiums. Data were collected on tort law from 1991 through 2004, and multivariate regression models, including fixed effects for state and year, were used to estimate the effect of changes in tort law on medical malpractice premiums. The premium consequences of national policy changes were simulated.

A cost-benefit analysis of risk-reduction strategies targeted at older drivers.

Objective: The risk of motor-vehicle collisions increases as driving-related functional abilities decline. These declines can accompany normal or pathological aging and can be identified through driving-related functional screening exams upon license renewal. The objective of this cost-benefit analysis was to determine the utility of four functional screening procedures used to identify drivers at risk for motor-vehicle collisions, as well as an intervention designed to maintain or improve functional abilities.

Relationship among hospital ERCP volume, length of stay, and technical outcomes.

Background: The relationship between hospital procedure volume and outcome has been recognized for various specialties and procedures. Although increasingly used and in existence for 40 years, to date, data on the relationship between hospital volume and outcome of ERCP are scant.

Objective: We sought to examine health-related outcomes after ERCP in relation to hospital procedure volume.

Patterns and predictors of home health and hospice use by older adults with cancer.

Objectives: To describe patterns of home health and hospice use by older cancer patients and a comparison group of older persons without cancer. To identify predictors of home care and hospice utilization.

Design: Retrospective analysis using the Surveillance, Epidemiology and End Results (SEER)-Medicare Database, a linkage of the SEER Program of the National Cancer Institute (an epidemiological surveillance system of population-based tumor registries) and Medicare Claims.

Economical and clinical outcomes of alternative treatment strategies in the management of common bile duct stones in the elderly: wait and see or surgery?

Background: Common bile duct stones (CBDS) are especially prevalent in the elderly population. Although the standard of care for stone removal is endoscopic retrograde cholangiography with sphincterotomy (ERC-S), the clinician's decision to refer a patient for cholecystectomy after ERC-S depends on several factors including potential for future biliary symptoms and complications, morbidity and mortality related to cholecystectomy, and costs associated with referral for cholecystectomy versus conservative approach. Using decision analysis, we explored the economic implications of cholecystectomy versus expectant management following ERC-S in elderly patients with CBDS.

Selective activation of PPARgamma in breast, colon, and lung cancer cell lines.

Peroxisome proliferator-activated receptor gamma (PPARgamma) plays a critical albeit poorly defined role in the development and progression of several cancer types including those of the breast, colon, and lung. A PPAR response element (PPRE) reporter assay was utilized to evaluate the selective transactivation of PPARgamma in 10 different cell lines including normal mammary epithelial, breast, lung, and colon cancer cells. Cells were treated with one of four compounds including rosglitizone (Ros), ciglitizone (Cig), 15-deoxy-Delta(12,14)-prostaglandin J2 (PGJ2), or GW 9662 (GW).

A cost-minimization analysis of alternative strategies in diagnosing pancreatic cancer.

Background: Several modalities currently exist for tissue confirmation of suspected pancreatic cancer prior to therapy. Since there is a paucity of cost-minimization studies comparing these different biopsy modalities, we analyzed costs and examined effectiveness of four alternative strategies for diagnosing pancreatic cancer.

Methods: A decision analysis model of patients with suspected pancreatic cancer was constructed.

The increased expression of peroxisome proliferator-activated receptor-gamma1 in human breast cancer is mediated by selective promoter usage.

Peroxisome proliferator-activated receptor-gamma1 (PPARgamma1) is transactivated by a wide range of ligands in normal human mammary epithelial and breast cancer cells. Although transactivation of PPARgamma mediates the expression of genes that are markers of differentiation, its overexpression in cancers of the breast, thyroid, colon, and lung suggests its dysregulation may play a role in oncogenesis, cancer progression, or both. We report the overexpression of PPARgamma is caused by the use of a tumor-specific promoter in breast cancer cells that is distinct from the promoter used in normal epithelia.

Incremental treatment costs in national cancer institute-sponsored clinical trials.

Context: Concern about additional costs for direct patient care impedes efforts to enroll patients in clinical trials. But generalizable evidence substantiating these concerns is lacking.

Objective: To assess the additional cost of treating cancer patients in the National Cancer Institute (NCI)-sponsored clinical trials in the United States across a range of trial phases, treatment modalities, and patient care settings.

Participation of patients 65 years of age or older in cancer clinical trials.

Purpose: Although 61% of new cases of cancer occur among the elderly, recent studies indicate that the elderly comprise only 25% of participants in cancer clinical trials. Further investigation into the reasons for low elderly participation is warranted. Our objective was to evaluate the participation of the elderly in clinical trials sponsored by the National Cancer Institute (NCI) and assess the impact of protocol exclusion criteria on elderly participation.

Signal cross-talk between estrogen receptor alpha and beta and the peroxisome proliferator-activated receptor gamma1 in MDA-MB-231 and MCF-7 breast cancer cells.

We have previously demonstrated that peroxisome proliferator-activated receptor gamma (PPARgamma) is expressed and transcriptionally responsive to both synthetic and natural ligands in a variety of human breast cancer cells. We also observed significant differences in basal and ligand-mediated transactivation of PPARgamma in cells with variable expression of the estrogen receptor. While previous reports indicate that PPARgamma can mediate the expression of estrogen target genes, no data have suggested that estrogen receptor (ER) expression can alter the transcriptional regulation of PPARgamma target gene expression.

Oxa-enediynes: probing the electronic and stereoelectronic contributions to the Bergman cycloaromatization.

Efficient routes to three classes of 10-membered oxa-enediynes are presented. The electronic and stereoelectronic contributions to half-lives are supported by density functional theory calculations. One member of this class cyclizes to give an isochroman which binds to and degrades the aryl hydrocarbon receptor (AhR).

Target-directed enediynes: designed estramycins.

The goal of selective targeting of enediyne cytotoxins has been investigated using estrogenic delivery vehicles. A series of estrogen-enediyne conjugates were assembled, and affinity for human estrogen receptor [hERalpha] was determined. The most promising candidate induced receptor degradation following Bergman cycloaromatization and caused inhibition of estrogen-induced transcription in T47-D human breast cancer cells.

Measuring the incremental cost of clinical cancer research.

Purpose: To summarize evidence on the costs of treating patients in clinical trials and to describe the Cost of Cancer Treatment Study, an ongoing effort to produce generalizable estimates of the incremental costs of government-sponsored cancer trials.

Methods: A retrospective study of costs will be conducted with 1,500 cancer patients recruited from a randomly selected sample of institutions in the United States. Patients accrued to either phase II or phase III National Cancer Institute-sponsored clinical trials during a 15-month period will be asked to participate in a study of their health care utilization (n = 750).

Differential transcriptional activation of peroxisome proliferator-activated receptor gamma by omega-3 and omega-6 fatty acids in MCF-7 cells.

While the role of dietary fats in breast cancer remains controversial, the recent cloning of peroxisome proliferator-activated receptor gamma (PPARgamma), a nuclear hormone receptor, from human breast cancer cells lines provides a potential molecular link. Several fatty acids from four classes of dietary fats were tested for their ability to mediate the transcriptional activity of PPARgamma in MCF-7 and MDA-MB-231 cells using growth media with minimal serum. Whereas omega-3 fatty acids inhibit transactivation of PPARgamma to levels below control, omega-6, monounsaturated and saturated fatty acids stimulate the activity of the transcriptional reporter.

Estimating costs and turnaround times: presenting a user-friendly tool for analyzing costs and performance.

A review of the literature finds wide variation in the costs and turnaround times associated with central laboratories, satellite laboratories, and point-of-care testing. The greatest variation occurs when comparing options for blood gas and electrolyte testing. Some variation can be attributed to costing methods, but substantial variation arises from circumstances under which testing is undertaken in specific sites.