Vascular ligand-receptor mapping by direct combinatorial selection in cancer patients.

Molecules differentially expressed in blood vessels among organs or between damaged and normal tissues, are attractive therapy targets; however, their identification within the human vasculature is challenging. Here we screened a peptide library in cancer patients to uncover ligand-receptors common or specific to certain vascular beds. Surveying ~2.35 x 10(6) motifs recovered from biopsies yielded a nonrandom distribution, indicating that systemic tissue targeting is feasible. High-throughput analysis by similarity search, protein arrays, and affinity chromatography revealed four native ligand-receptors, three of which were previously unrecognized. Two are shared among multiple tissues (integrin α4/annexin A4 and cathepsin B/apolipoprotein E3) and the other two have a restricted and specific distribution in normal tissue (prohibitin/annexin A2 in white adipose tissue) or cancer (RAGE/leukocyte proteinase-3 in bone metastases). These findings provide vascular molecular markers for biotechnology and medical applications.

Wide variation in content of inpatient do-not-resuscitate order forms used at National Cancer Institute-designated cancer centers in the United States.

GOALS OF WORK: Determining resuscitation status (RS) for inpatients with advanced cancer is emotionally charged and often conflictual. Available data suggest that clinicians have inconsistent practices when establishing and documenting do-not-resuscitate (DNR) orders. Lack of standardization may contribute to ineffective and unclear discussions regarding RS. To inform revisions of DNR order forms used at one comprehensive cancer center, we surveyed National Cancer Institute-designated cancer centers (NCICCs) to determine if a standardized approach to documenting inpatient DNR orders exists. MATERIALS AND METHODS: Over a 12-week period in 2002-2003, the 50 NCICCs providing inpatient care were contacted regarding participation in this Institutional Review Board-approved study. Using a 69-item database, inpatient DNR order forms were analyzed for content and elements of process used to establish and document RS. Each form was evaluated by two raters to assess inter-rater reliability. Analysis was descriptive; inter-rater agreement was summarized using the kappa statistic. MAIN RESULTS: Sixty percent (30 out of 50) of NCICCs participated. Eighty percent of responding sites confined the order process exclusively to cardiopulmonary resuscitation and did not include other interventions for possible limitation. Two thirds of responding sites used preformatted order forms specific for establishing inpatient RS; forms varied widely in content and elements of process used to establish and document DNR orders. CONCLUSIONS: NCICCs do not have a standardized approach to establishing and documenting DNR orders. Lack of standardization may reflect the absence of a common understanding of these difficult issues which may contribute to unclear and ineffective communication when addressing RS.

Phase I participants' views of quality of life and trial participation burdens.

PURPOSE: Participants' perception of quality of life (QOL) and respondent burden have significant implications for investigators' ethical responsibilities to their subjects in phase I cancer trials. To address these responsibilities, analysis was conducted on participants' views of their experiences of a phase I trial, including the associated burdens and what constitutes QOL. PATIENTS AND METHODS: One hundred potential participants of the endostatin trial were surveyed. Sixteen of the 18 trial participants were interviewed extensively about their experiences on the trial. RESULTS: Participants described 'normality' as a baseline ability to function, be productive, and be free from symptoms of disease and side effects of treatment. Reflecting the relative nontoxicity of the study drug, participants contrasted their current QOL with their negative experience of previous cancer treatments and viewed their QOL as fairly good. However, participants emphasized that indirect and procedural burdens of trial participation had a significant impact on their current QOL. CONCLUSIONS: Candid descriptions of a trial's practical demands, in addition to potential physical complications in a trial, could improve the quality of informed consent.

Revisiting ethical guidelines for research with terminal wean and brain-dead participants.

Some research is too risky to be conducted on anyone with a life expectancy of more than a few hours. Yet under some circumstances, the research can still be carried out by using subjects who are either brain dead or are soon to undergo a terminal wean, and who have articulated values that inclusion in the study can honor. So argues a team of ethicists and researchers at M.D. Anderson Cancer Center, where such research was recently undertaken.

Study of the media's potential influence on prospective research participants' understanding of and motivations for participation in a high-profile phase I trial.

PURPOSE: To describe prospective participants' initial source of information about, understanding of, and motivation to participate in a phase I clinical trial of the antiangiogenesis agent human recombinant endostatin. PATIENTS AND METHODS: We surveyed 100 of 130 persons referred to the endostatin trial between October 1999 and November 2000 and analyzed media coverage of the agent from 1997 to 2000. RESULTS: Forty-seven percent of survey respondents first heard about the trial from media reports. Fifty-one percent of these subsequently contacted their physicians. Thirty-three percent of respondents correctly understood the purpose of the trial. Seventy-nine respondents were interviewed before they met trial investigators to discuss the trial. Of these, those who first heard about endostatin from the media were five times more likely to understand correctly the trial's purpose than those who first heard from other sources. Seventy-four percent (70 of 95) of respondents cited hope for personal benefit as the main reason for their willingness to enroll. Those who first heard about endostatin from the media were no more motivated by hope of personal benefit (77%) than those who first heard from other sources (71%) (P =.46). Ninety-nine percent of all respondents cited "joining the study gives me hope" as a contributing factor in their decision making about the trial. CONCLUSION: Media coverage prompted prospective participants to contact their physicians but did not seem to hinder understanding nor could it be shown to heighten their hope for personal benefit.