Boron Neutron Capture Therapy (BNCT) Mediated by Maleimide-Functionalized Closo-Dodecaborate Albumin Conjugates (MID:BSA) for Oral Cancer: Biodistribution Studies and In Vivo BNCT in the Hamster Cheek Pouch Oral Cancer Model.

BACKGROUND: BNCT (Boron Neutron Capture Therapy) is a tumor-selective particle radiotherapy that combines preferential boron accumulation in tumors and neutron irradiation. Although p-boronophenylalanine (BPA) has been clinically used, new boron compounds are needed for the advancement of BNCT. Based on previous studies in colon tumor-bearing mice, in this study, we evaluated MID:BSA (maleimide-functionalized closo-dodecaborate conjugated to bovine serum albumin) biodistribution and MID:BSA/BNCT therapeutic effect on tumors and associated radiotoxicity in the hamster cheek pouch oral cancer model. METHODS: Biodistribution studies were performed at 30 mg B/kg and 15 mg B/kg (12 h and 19 h post-administration). MID:BSA/BNCT (15 mg B/kg, 19 h) was performed at three different absorbed doses to precancerous tissue. RESULTS: MID:BSA 30 mg B/kg protocol induced high BSA toxicity. MID:BSA 15 mg B/kg injected at a slow rate was well-tolerated and reached therapeutically useful boron concentration values in the tumor and tumor/normal tissue ratios. The 19 h protocol exhibited significantly lower boron concentration values in blood. MID:BSA/BNCT exhibited a significant tumor response vs. the control group with no significant radiotoxicity. CONCLUSIONS: MID:BSA/BNCT would be therapeutically useful to treat oral cancer. BSA toxicity is a consideration when injecting a compound conjugated to BSA and depends on the animal model studied.

Optimization of the classical oral cancerization protocol in hamster to study oral cancer therapy.

OBJECTIVE(S): The hamster carcinogenesis model recapitulates oral oncogenesis. Dimethylbenz[a]anthracene (DMBA) cancerization induces early severe mucositis, affecting animal's welfare and causing tissue loss and pouch shortening. "Short" pouches cannot be everted for local irradiation for boron neutron capture therapy (BNCT). Our aim was to optimize the DMBA classical cancerization protocol to avoid severe mucositis, without affecting tumor development. We evaluated BNCT in animals cancerized with this novel protocol. MATERIALS AND METHODS: We studied: Classical cancerization protocol (24 applications) and Classical with two interruptions (completed at the end of the cancerization protocol). BNCT mediated by boronophenylalanine (BPA) was performed in both groups. RESULTS: The twice-interrupted group exhibited a significantly lower percentage of animals with severe mucositis versus the non-interrupted group (17% versus 71%) and a significantly higher incidence of long pouches (100% versus 53%). Tumor development and the histologic characteristics of tumor and precancerous tissue were not affected by the interruptions. For both groups, overall tumor response was more than 80%, with a similar incidence of BNCT-induced severe mucositis. CONCLUSION(S): The twice-interrupted protocol reduced severe mucositis during cancerization without affecting tumor development. This favored the animal's welfare and reduced the number of animals to be cancerized for our studies, without affecting BNCT response.

Habitat use and demography of Mus musculus in a rural landscape of Argentina.

The main goal of the paper was to determine the habitat distribution of the house mouse (Mus musculus) within a rural landscape of Buenos Aires province, Argentina. We also studied the seasonal variation in abundance and reproductive activity. The habitats studied were poultry farms, human houses in a small village, cropfields, pastures, cropfield and pasture edges, riparian habitats (streams), railway embankments and woodlots. We captured 817 M. musculus and 690 individuals of 5 native rodent species. M. musculus was captured in poultry farms, houses, riparian habitats, cropfield and borders, but it showed a significantly higher abundance in poultry farms compared to the other habitats. Its presence outside poultry farms was significantly related to the distance to streams and poultry farms. The mean trapping success index of M. musculus did not show significant variations between periods, but the proportion of active males was significantly higher in the spring-summer period than in the autumn-winter period. All captures of M. musculus in cropfields, borders and riparian habitats occurred in the spring-summer period. The capture of M. musculus in many types of habitats suggests that it can disperse outside poultry farms, and streams may be used as corridors.

Bromadiolone susceptibility in wild and laboratory Mus musculus L.(house mice) in Buenos Aires, Argentina.

BACKGROUND: Rodents are major pests in many agricultural systems, where they can cause significant economic losses and involve a sanitary risk. The application of anticoagulant rodenticides for rodent control has showed a decrease in effectiveness through time because of the development of resistant populations and the development of aversion behaviour. The goal of the present study was to test the susceptibility to bromadiolone and the existence of anticoagulant resistance in Mus musculus L. (house mouse) in Argentina. We conducted a feeding test with wild animals captured in poultry farms and a laboratory strain that were fed with bromadiolone bait. RESULTS: Three animals of the field experimental group survived the 21 days study period, while for laboratory animals mortality was 100%. Control field animals which were fed without anticoagulant showed 100% survival. CONCLUSION: We found evidence of the presence of anticoagulant resistant M. musculus L. in the study area. Feeding behaviour may have contributed to increasing the time of survival, and may be a mechanism that allows metabolic clearance of the bromadiolone. Under field conditions control with anticoagulants would be less effective because animals have alternative food.