Chronic stress increases experimental pancreatic cancer growth, reduces survival and can be antagonised by beta-adrenergic receptor blockade.

BACKGROUND/OBJECTIVES: Chronic stress could promote tumour growth and reduce survival of pancreatic cancer patients via beta-adrenergic receptors of tumour cells. We have tested the impact of chronic acoustic and restraint stress on tumour development in an orthotopic syngeneic murine model of pancreatic cancer. METHODS AND RESULTS: Tumour-bearing C57BL/6 mice exposed to chronic stress had 45% (p = 0.0138) higher circulating steroid and 111% (p = 0.0052) higher adrenal tyrosine hydroxylase levels. Their immune response was significantly suppressed: The in vitro LPS response of splenocytes was significantly reduced regarding Th1- and Th2-cytokines including IFN-gamma, IL-6, IL-10 and MCP-1 (0.0011 < p < 0.043). Also, tumours of stressed mice showed a tendency towards fewer total CD4 cells, more regulatory T cells (Treg), less T cell/tumour cell contacts and a reduction of CTLA-4 in CD4 cells (p > 0.05). TGF-beta in vitro was increased by 23.4% using catecholamines (p < 0.012) and in vivo employing chronic stress (p < 0.001). After 5 weeks tumour volumes were 130% (p = 0.0061) larger and median survival reduced by 13.5% (p = 0.0058). Tumours expressed more VEGF (p = 0.0334), had greater microvessel densities (p = 0.047), and an increased MMP-9 expression (p = 0.0456). Beta-catecholamines increased proliferation in tumour cells by 18% (p < 0.0001) and migration by 78% (p = 0.0348) whereas the beta-blocker propranolol reduced these effects by 25% (p < 0.0001) and 53% (p = 0.045), respectively. When stressed tumour-bearing animals were treated with propranolol tumour volumes were reduced by 69% (p = 0.0088) and survival improved by 14% (p < 0.0058). CONCLUSIONS: The potential treatment with beta-blockers of patients with pancreatic cancer or other malignancies should be further evaluated as an adjuvant anti-neoplastic agent in clinical trials.

Recruiting for caregiver education research: perspectives of caregivers of people with multiple sclerosis.

Caregiver education programs can support participants in a role that is often challenging. Research is needed to determine the effectiveness of these programs; however, recruitment for such studies can be difficult. The objectives of this study were to explore 1) how multiple sclerosis (MS) caregivers respond to recruitment materials for a research study evaluating a caregiver education program, including aspects of the materials that encourage or discourage their interest in participation; and 2) what recommendations MS caregivers have for improving study recruitment advertising. Qualitative interviews were conducted with seven MS caregivers. Participants were asked about their reactions to advertisements for a pilot study intended to evaluate an MS caregiver education program. Participants were also asked to reflect on factors that would influence their decision to participate in the program and to provide suggestions to improve recruitment materials. Data were analyzed using a constant-comparative approach. Study findings indicated that the language and visual design of the advertisements influenced the participants' initial responses. Some caregivers first responded to the fact that the program was part of a research study, and these caregivers had overall negative responses to the advertising, such as concern that the program was being "tested." Other caregivers first considered the personal relevance of the program. These caregivers had neutral-to-positive responses to the flyers and weighed the relevance of the program against the research and logistical aspects. Participants provided recommendations to improve the recruitment materials. While recruiting for caregiver education research can be challenging, piloting recruitment materials and using a variety of advertising options may improve response.