Platelet-activating factor receptor (PAF-R)-dependent pathways control tumour growth and tumour response to chemotherapy

<p>Abstract</p> <p>Background</p> <p>Phagocytosis of apoptotic cells by macrophages induces a suppressor phenotype. Previous data from our group suggested that this occurs via Platelet-activating factor receptor (PAF-R)-mediated pathways. In the present study, we investigated the impact of apoptotic cell inoculation or induction by a chemotherapeutic agent (dacarbazine, DTIC) on tumour growth, microenvironmental parameters and survival, and the effect of treatment with a PAF-R antagonist (WEB2170). These studies were performed in murine tumours: Ehrlich Ascitis Tumour (EAT) and B16F10 melanoma.</p> <p>Methods</p> <p>Tumour growth was assessed by direct counting of EAT cells in the ascitis or by measuring the volume of the solid tumour. Parameters of the tumour microenvironment, such as the frequency of cells expressing cyclo-oxygenase-2 (COX-2), caspase-3 and galectin-3, and microvascular density, were determined by immunohistochemistry. Levels of vascular endothelium growth factor (VEGF) and prostaglandin E2 (PGE2) were determined by ELISA, and levels of nitric oxide (NO) by Griess reaction. PAF-R expression was analysed by immunohistochemistry and flow cytometry.</p> <p>Results</p> <p>Inoculation of apoptotic cells before EAT implantation stimulated tumour growth. This effect was reversed by <it>in vivo </it>pre-treatment with WEB2170. This treatment also reduced tumour growth and modified the microenvironment by reducing PGE2, VEGF and NO production. In B16F10 melanoma, WEB2170 alone or in association with DTIC significantly reduced tumour volume. Survival of the tumour-bearing mice was not affected by WEB2170 treatment but was significantly improved by the combination of DTIC with WEB2170. Tumour microenvironment elements were among the targets of the combination therapy since the relative frequency of COX-2 and galectin-3 positive cells and the microvascular density within the tumour mass were significantly reduced by treatment with WEB2170 or DTIC alone or in combination. Antibodies to PAF-R stained the cells from inside the tumour, but not the tumour cells grown <it>in vitro</it>. At the tissue level, a few cells (probably macrophages) stained positively with antibodies to PAF-R.</p> <p>Conclusions</p> <p>We suggest that PAF-R-dependent pathways are activated during experimental tumour growth, modifying the microenvironment and the phenotype of the tumour macrophages in such a way as to favour tumour growth. Combination therapy with a PAF-R antagonist and a chemotherapeutic drug may represent a new and promising strategy for the treatment of some tumours.</p

Influência da fase embrionária dos ovos da traça-das-crucíferas sobre fêmeas de Trichogramma pretiosum com diferentes idades Influence of diamondback moth embrionary egg stage on Trichogramma pretiosum females of different ages

Plutella xylostella é considerada a praga mais importante das crucíferas. O método de controle mais utilizado para essa praga é o químico. Contudo, esta espécie de inseto vem desenvolvendo resistência aos inseticidas aplicados. O controle biológico com espécies do gênero Trichogramma é considerado uma alternativa no controle dessa praga. Porém, poucos são os trabalhos que mencionam aspectos biológicos desse parasitóide sobre esta praga. Neste trabalho avaliou-se a influência da fase embrionária dos ovos do hospedeiro P. xylostella sobre fêmeas de T. pretiosum com diferentes idades. Fêmeas do parasitóide foram divididas em cinco lotes, compostos por espécimes recém-emergidos com 24; 48; 72 e 96 horas de idade. Cada lote continha dez fêmeas de T. pretiosum. Para cada fêmea de cada lote, foi oferecida uma cartela contendo 30 ovos de P. xylostella com um, dois e três dias de idade. As maiores taxas de parasitismo foram observadas em fêmeas com idade superior a 48 horas, independente do desenvolvimento embrionário do hospedeiro. Em ovos com três dias de desenvolvimento embrionário verificou-se que, para fêmeas recém-emergidas e com 48 horas de idade, a taxa de viabilidade foi superior apenas em relação àquelas com 96 horas de idade. Ao se avaliar os descendentes de T. pretiosum provenientes de ovos com um dia de desenvolvimento embrionário, verificou-se que os maiores valores de longevidade foram obtidos quando as fêmeas desse parasitóide eram recém-emergidas.<br>Plutella xylostella is one of the most important pests of Cruciferae. Chemicals have been used to control this insect, but the rapid development of resistance is a serious constraint to this method. Biological control with Trichogramma species has been reported as an alternative to control diamondback moth. However few works report biological parameters of this parasitoid interacting with this pest. This work was carried out to evaluate the influence of egg embryonary stage of P. xylostella on T. pretiosum females at different ages. Females of this parasitoid were organized in five groups. These groups were composed of females just emerged, 24 h; 48 h; 72 h, and 96 hours-old. Each group was formed of ten females. Each female received a card with thirty P. xylostella eggs, one, two and three day-old. Higher parasitism rates were observed with females older than 48 hours, with no influence of host embryonic development. In three day-old eggs it was verified that just emerged females and 48 hour-old, the viability index was superior just to those 96 hour-old. The progeny with one day of embryonary development, presented higher longevity values with just emerged females