Leucurogin and melanoma therapy.

Leucurogin is an ECD disintegrin-like protein, cloned from Bothrops leucurus venom gland. This new protein, encompassing the disintegrin region of a PIII metalloproteinase, is produced by recombinant technology and its biological and functional activity was partially characterized in this study. Biological activity was characterized in vitro using human fibroblasts. Functional activity of leucurogin was analysed in vitro and in vivo with murine B16F10 Nex-2 and human melanoma BLM cells. The results show that leucurogin inhibits cellular processes dependent on collagen type I. In a competition assay with collagen, leucurogin inhibits, in a dose-dependent manner, the adhesion of fibroblast to collagen. At 10 µM leucurogin reduces adhesion (40%) and migration (70%) of hFb and inhibits migration (32%) and proliferation (65%) of BLM cells. At 2.5 µM leucurogin inhibits 80% cell proliferation of B16F10 Nex-2 melanoma cells. At 4.8 µM leucurogin inhibits, in vitro, the vascular structures formation by endothelial cells by 66%. Leucurogin, injected intraperitoneally, i.p. (5 µg/animal, two-month old C57/Bl6 male mice) on alternate days for 15 days, inhibits lung metastasis of B16F10 Nex-2 cells by 70-75%. In the treatment of human melanoma, grafted intradermally in the nude mice flank, leucurogin (7.5 µg/kg in alternate days during 17 days) inhibits tumor growth by more than 40%. Leucurogin can be considered a promising agent for melanoma treatment.

Duration of spermatogenesis and daily sperm production in the rodent Proechimys guyannensis.

The spiny rat (Proechimys guyannensis) is a neotropical rodent that is used in biomedical research, particularly research related to chronic resistance to epilepsy and infectious diseases. To our knowledge, there are few reports concerning the reproductive biology of this species. Therefore, besides providing basic biometric and morphometric data, in the present study we investigated testis function and spermatogenesis in adult spiny rats. The mean testis weight and gonadosomatic index obtained were 1.63 ± 0.2 g and 1.15 ± 0.1% respectively. Based on the development of the acrosomic system, 12 stages of the seminiferous epithelium cycle were characterized. Stages VI and VII presented the highest frequencies (~17-19%), whilst stages II to V showed the lowest frequencies (~2-4%). The most advanced germ cell types labelled at 1 h or 20 days after BrdU injections were respectively preleptotene/leptotene spermatocytes at stage VII and elongated spermatids at stage III. The mean duration of one cycle was 7.5 ± 0.01 days and the entire spermatogenic process lasted 33.7 ± 0.06 days (~4.5 cycles). The seminiferous tubules (ST) occupied ~96 ± 1% of the testis parenchyma, whereas Leydig cells comprised only 1.5 ± 0.4%. The number of Sertoli cells (SC) per testis gram and the SC efficiency (spermatids/SC) were respectively 78 × 106 ± 11 × 106 and 7.9 ± 1. The daily sperm production per testis gram (spermatogenic efficiency; daily sperm production (DSP)/g/testis) was 78 × 106 ± 8 × 106. To our knowledge, this spermatogenic efficiency is among the highest found for mammals investigated to date and is probably related to the very short duration of spermatogenesis and the very high ST percentage and SC number obtained for this species.

Swim training suppresses tumor growth in mice.

The present study was designed to determine the effects of physical training on the development of cancer induced by the injection of Ehrlich tumor cells in mice. Male Swiss mice were subjected to a swim training protocol (5 days/wk for 6 wk, 1 h at 50% of maximal capacity-trained groups) or remained sedentary in their cages (sedentary groups). The inoculation of Ehrlich tumor cells was performed at the end of the fourth week, and animals were killed after 6 wk of training. Heart and solid tumor weights were recorded, and tumor volumes were calculated. Portions of the tumors were used for the evaluation of macrophages and neutrophil accumulation or fixed in neutral 10% buffered formalin for histological analysis. The tumor volume and weight were, respectively, approximately 270% and 280% greater in sedentary mice than in trained mice. Macrophage infiltration in the tumor tissue was significantly lower in trained mice (0.65 +/- 0.16 vs. 1.78 +/- 0.43 macrophages x 10(3) in the sedentary group). Moreover, neutrophil accumulation in tumors was slightly reduced after exercise training, and the amount of tumor cells was reduced in trained mice. Exercise capacity was substantially increased in trained mice, as determined by a 440% increase in the exercise time at 50% of maximal capacity. In summary, swim training retarded the development of Ehrlich tumors in mice, accompanied by a reduction in macrophage infiltration and neutrophil accumulation. These findings provide conceptual support for clinical observations that controlled physical activities may be a therapeutically important approach to preventing cancer progression and may improve the outcome of cancer treatment.