Synergistic activity of recombinant human endostatin in combination with adriamycin: analysis of in vitro activity on endothelial cells and in vivo tumor progression in an orthotopic murine mammary carcinoma model.

PURPOSE: Current combination treatment strategies in malignancy are designed to evaluate the use of cytotoxic drugs and antiangiogenic agents. Endostatin, a fragment of collagen XVIII, specifically inhibits proliferation, migration, and differentiation of endothelial cells in vitro as well as angiogenesis and tumor progression in in vivo models. In this study, we determine the antitumor effect of rhEndostatin administered alone or in combination with Adriamycin against established orthotopic murine mammary carcinoma. EXPERIMENTAL DESIGN: Mice bearing orthotopically established DA-3 mammary adenocarcinoma tumors received varying doses of rhEndostatin alone and in combination with Adriamycin to assess tumor growth inhibition. Additional studies of this in vivo combination included a determination of Adriamycin-induced cardiotoxicity and in vitro effects on human umbilical vein endothelial cell proliferation and cord formation. RESULTS: For single-agent activity, optimal tumor growth inhibition was observed after s.c. administration of 50 mg/kg/day rhEndostatin or 5 mg/kg Adriamycin injected i.v. every 4 days. Combination of Adriamycin with optimal or suboptimal doses of rhEndostatin resulted in synergistic inhibition of DA-3 tumor growth. Importantly, unlike other antiangiogenic agents, rhEndostatin did not exacerbate the cardiotoxicity of Adriamycin. The synergistic interaction between rhEndostatin and Adriamycin was also observed in vitro for inhibition of human umbilical vein endothelial cell proliferation and inhibition of cord formation. CONCLUSIONS: These data suggest that the synergy observed with rhEndostatin in combination with Adriamycin is exerted at the level of the endothelial cell and can result in enhanced tumor growth inhibition. The potential benefit of Adriamycin used in combination with rhEndostatin is being considered for clinical evaluation.     

Future health of AYA survivors

Adolescent and young adult (AYA) oncology patients (ages 15–39) have been identified as a group with healthcare disparities including gaps and challenges in diagnosis, access to care, research, clinical trial participation, and cure rates. Like other patient groups with cancer or other chronic illnesses, disparities can lead to poor future health and outcomes, which is a well‐recognized concern within the AYA population. Cancer is the leading disease‐related cause of death in this age range. Numerous interested groups including the National Cancer Institute have met to address the research and cancer care needs of AYAs. This review highlights how these gaps in care during and after treatment can affect future health of this population of patients. Access to care, models of survivorship care, and lack of provider education are discussed. Survivorship care and use of guidelines, and promotion of psychosocial support and health behaviors during treatment and beyond are essential to optimizing future health of AYA patients.     

Development and validation of the Workplace Interruptions Measure

In 3 studies, we developed and tested the first comprehensive, self‐report measure of workplace interruptions. The Workplace Interruptions Measure (WIM) is based on a typology of interruptions that included intrusions, distractions, discrepancy detections, and breaks. The four‐factor structure was reduced to a 12‐item measure in Study 1 (N = 317) and confirmed in a diverse sample of employees in Study 2 (N = 160). Study 3 (N = 323) further examined the psychometric properties of the WIM in a sample of university faculty and staff. Studies 2 and 3 demonstrated that both effort‐enhancing interruptions (intrusions, distractions, and discrepancy detections) and recovery‐enhancing interruptions (breaks) were associated with stressors and strains. Distractions, discrepancy detections, and breaks uniquely predicted strain outcomes beyond other workplace stressors (i.e., quantitative workload, interpersonal conflict, and role conflict). We discuss implications of the WIM for the theory and practice of interruptions research.     

Examining protective factors and risk factors in urban and rural head start Preschoolers

This study examined a comprehensive screening model within children attending Head Start programs from urban (n =232) and rural (n = 231) communities. The Devereux Early Childhood Assessment (DECA; LeBuffe & Naglieri, 1999 ) was used to measure social‐emotional protective factors (i.e., Total Protective Factors [TPF]) and risk factors (i.e., Behavior Concerns [BC]) within children that resided in two different community settings. Children from low‐income rural programs received higher scores on a subscale measuring children's relationship to adults (i.e., Attachment subscale). Additionally, children from low‐income urban programs received higher scores on children's ability to self‐regulate (i.e., Self‐Control subscale). Significant differences between children from rural and urban settings were not found on the primary scales (BC or TPF) of the DECA. Statistically significant gender differences by community‐type were not found. Findings contribute to the literature by illustrating that community characteristics might influence the development of different social‐emotional behaviors in preschool children. © 2011 Wiley Periodicals, Inc.     

Performance of Older Depressed Patients on Two Cognitive Malingering Tests: False Positive Rates for the Rey 15-item Memorization and Dot Counting Tests

To our knowledge, no investigations have been undertaken to determine whether depression impacts performance on two commonly used tests to detect malingering of cognitive symptoms, the Rey 15-item Memorization Test and the Rey Dot Counting Test. This is a critical issue because of the high rate of depressive symptoms in patients with neurological conditions. It was hypothesized that depressed individuals, especially those with more severe depression, might be at risk for failing the tests, because these patients exhibit mild deficits in mental speed, visual perceptual/spatial skills, and visual memory, abilities required for successful completion of the malingering tests. However, examination of test performance in 64 older participants with major depression generally revealed very low false positive rates for most test scores, and severity of depression was unrelated to test scores. These results add to accumulating data supporting the validity of these cognitive malingering tests by documenting few false positive identifications.     

Specialized Care of Women and Newborns Affected by Opioids With a CORE Team of Nurses

Staff on a mother–baby unit of a large suburban Level II facility identified the need to provide specialized nursing care to women affected by opioids. The manager of the unit recognized inconsistencies in care and frustration expressed by women and staff. She recruited a CORE (Champion for our Opiate patients using Respectful and Relevant Engagement and Education) group of staff nurses to care for these women. CORE nurses received specialized education and resources and served as the primary nurses for women admitted to the unit with a positive urine drug screening result or a history of drug use during pregnancy. Having a CORE team has brought a consistent approach when providing care to families affected by opioids.