RESUMO
Immunosuppressive cells in the tumor microenvironment allow cancer cells to escape immune recognition and support cancer progression and dissemination. To improve therapeutic efficacy, we designed a liposomal oxaliplatin formulation (PCL8-U75) that elicits cytotoxic effects toward both cancer and immunosuppressive cells via protease-mediated, intratumoral liposome activation. The PCL8-U75 liposomes displayed superior therapeutic efficacy across all syngeneic cancer models in comparison to free-drug and liposomal controls. The PCL8-U75 depleted myeloid-derived suppressor cells and tumor-associated macrophages in the tumor microenvironment. The combination of improved cancer cell cytotoxicity and depletion of immunosuppressive populations of immune cells is attractive for combination with immune-activating therapy. Combining the PCL8-U75 liposomes with a TLR7 agonist induced immunological rejection of established tumors. This combination therapy increased intratumoral numbers of cancer antigen-specific cytotoxic T cells and Foxp3- T helper cells. These results are encouraging toward advancing liposomal drug delivery systems with anticancer and immune-modulating properties into clinical cancer therapy.
Assuntos
Antineoplásicos , Neoplasias , Linhagem Celular Tumoral , Sistemas de Liberação de Medicamentos , Humanos , Fatores Imunológicos , Imunoterapia/métodos , Lipossomos , Neoplasias/tratamento farmacológico , Microambiente TumoralRESUMO
The aim was to compare the effectiveness of untailored text messages for smoking cessation to tailored text messages delivered at a higher frequency. From February 2007 to August 2009, 2030 users of an internet-based smoking cessation program with optional text message support aged 15-25 years were consecutively randomized to versions of the program that offered either tailored or untailored text messages. Thirty-day point abstinence from smoking was measured self-reportedly at 12-months follow-up. Response rates were 36.3% and 38.1% in the tailored and untailored group, respectively. We analyzed the entire study population, as well as those opting for text messages (n = 1619). In intention-to-treat analysis with multiple imputation of missing data, the odds ratio for 30-day point abstinence was 1.28 (95% CI 0.91-2.08) for the tailored compared with untailored messages. When restricting the analysis to those who had chosen to receive text messages, the corresponding odds ratio was 1.45 (95% CI 1.01-2.08). The higher long-term quit rates in the group receiving the tailored text messages compared with untailored text messages in the restricted analysis indicated that tailoring and higher frequency of text messages increases quit rates among young smokers.