Susceptibility of Melanoma Cells to Targeted Therapy Correlates with Protection by Blood Neutrophils.

Elevated levels of peripheral blood and tumor tissue neutrophils are associated with poorer clinical response and therapy resistance in melanoma. The underlying mechanism and the role of neutrophils in targeted therapy is still not fully understood. Serum samples of patients with advanced melanoma were collected and neutrophil-associated serum markers were measured and correlated with response to targeted therapy. Blood neutrophils from healthy donors and patients with advanced melanoma were isolated, and their phenotypes, as well as their in vitro functions, were compared. In vitro functional tests were conducted through nonadherent cocultures with melanoma cells. Protection of melanoma cell lines by neutrophils was assessed under MAPK inhibition. Blood neutrophils from advanced melanoma patients exhibited lower CD16 expression compared to healthy donors. In vitro, both healthy-donor- and patient-derived neutrophils prevented melanoma cell apoptosis upon dual MAPK inhibition. The effect depended on cell-cell contact and melanoma cell susceptibility to treatment. Interference with protease activity of neutrophils prevented melanoma cell protection during treatment in cocultures. The negative correlation between neutrophils and melanoma outcomes seems to be linked to a protumoral function of neutrophils. In vitro, neutrophils exert a direct protective effect on melanoma cells during dual MAPK inhibition. This study further hints at a crucial role of neutrophil-related protease activity in protection.

Refugees in Denver and their perceptions of their health and health care.

BACKGROUND: Colorado receives approximately 2,500 refugees each year from countries all over the world. We assessed the self-perceived health of and barriers to care for refugees in the Denver metro area in order to understand better the needs of this population. METHODS: A 61-item questionnaire was completed by a convenience sample of 120 local refugees between June and December of 2009. RESULTS: Only 10% of respondents reported their health as excellent, while 31% rated it as either poor or fair. The most prominent barriers to care included unemployment (91%), language (46%), lack of health insurance (41%), lack of transportation (43%), and distrust of doctors (22%). CONCLUSIONS: Our study suggests that refugees in Denver face significant barriers that affect their access to health care. Recommendations include improved job and language skill programs, a health navigator program, and health care provider training on culturally effective care of this population.