Perspectives of cancer prevention and control resources from stakeholders in rural southern Illinois.

PURPOSE: Rural residents have a higher cancer burden than urban residents, which is likely related to multiple socioecological factors. This study sought to investigate the perspectives of a diverse set of rural stakeholders regarding access to cancer prevention and control resources in rural southern Illinois. METHODS: Stakeholders were recruited from counties in southern Illinois and included residents (cancer survivors or caregivers), leaders of community-based organizations with health-related missions, and health care providers. Individual interviews and focus groups assessed recommended cancer prevention, control, and treatment resources; helpfulness of regional resources; and needed resources. The research team used an iterative approach to thematic analysis wherein codes were derived inductively and refined repeatedly to reveal overarching themes. FINDINGS: Forty-four stakeholders reported challenges to health care access (eg, travel distance, financial burdens, and poor quality of care) and limited access to supportive care services (lack of caregiver support and "spotty" area resources). To mitigate these barriers, local residents used a combination of individual (self-reliance and adaptive measures) and organizational (patient navigation and financial services) approaches. Finally, stakeholders reported multiple forms of cancer control and prevention communication, including formal discussions with health care providers and various types of informal social support (eg, friends and family). CONCLUSIONS: Stakeholders experienced barriers to cancer prevention and control often mitigated by a reliance on personal adaptations, nonclinical organizational supports, and informal support systems. While resources remain minimal in southern Illinois, researchers and practitioners must make efforts to leverage existing community organizations and social networks to improve cancer outcomes in this region.

CD62L as a therapeutic target in chronic lymphocytic leukemia.

PURPOSE: Despite advances in the treatment of chronic lymphocytic leukemia (CLL), the disease remains incurable with standard therapies and relapse is inevitable. A growing body of evidence indicates that alterations in the adhesion properties of neoplastic cells play a pivotal role in the development and progression of CLL. EXPERIMENTAL DESIGN: The expression of 71 cell surface molecules was examined on CLL peripheral blood mononuclear cells (PBMCs) over 3 weeks in culture. The most highly upregulated marker, CD62L, was examined further for expression on CD5(+)/CD19(+) CLL cells in vitro and in lymph node and bone marrow biopsies. The prosurvival role of CD62L was examined using a functional blocking antibody and therapeutic potential evaluated by comparison with current chemotherapy agents. RESULTS: Blocking CD62L resulted in apoptosis of CLL cells but not PBMCs from healthy donors suggesting a novel role for CD62L in CLL cell survival. The beneficial effect of coculturing CLL cells with bone marrow stromal cells or endothelial cells does not protect CLL cells from anti-CD62L-related toxicity. Moreover, combining fludarabine or mafosfamide with the anti-CD62L in vitro produced an additive effect both with and without stromal cells. CONCLUSION: This is the first reported data showing that blocking the activation and homing marker, CD62L, regulates CLL cell survival in vitro. These data also suggest that therapeutic antibodies against CD62L may provide additional clinical benefit to patients with CLL receiving current standard chemotherapy protocols.

CCL2 and CXCL2 enhance survival of primary chronic lymphocytic leukemia cells in vitro.

Chronic lymphocytic leukemia (CLL) is predominantly a disease of accumulation rather than rapid proliferation. To date, no cell lines exist, as CLL cells undergo rapid apoptosis when cultured in vitro, suggesting that a favorable in vivo microenvironment is required. To identify survival signals we cultured primary CLL peripheral blood mononuclear cells (PBMCs) at high density, which has previously been shown to dramatically improve survival. Using antibody arrays we measured the level of 42 cytokines in culture supernatants and showed that inerleukin-6 (IL-6), IL-8, CXCL2 and CCL2 were highly up-regulated in culture. This is the first report to describe a role for CCL2 and CXCL2 in CLL cell survival. Importantly, CXCL2, IL-6 and IL-8 were significantly up-regulated in primary patient plasma. The addition of either CXCL2 or CCL2 enhanced CLL cell survival, while antibodies blocking these chemokines reduced survival. Co-culture of CLL cells and PBMC accessory cells separated by transwells provided a similar degree of survival protection compared to normal culture, whereas CLL cells cultured alone died rapidly. Interestingly, CCL2 and CXCL2 appeared to be produced by CLL cells but only when co-cultured with accessory cells. Thus, we speculate that accessory cells release soluble factors that promote the production of these pro-survival chemokines from CLL cells and physical interactions are not required. Our data support the concept that the CLL microenvironment is critical, and suggests that soluble factors are more important than physical interactions.