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Capolla S.,University of Trieste | Garrovo C.,Institute for Maternal and Child Health IRCCS Burlo Garofolo | Zorzet S.,University of Trieste | Lorenzon A.,Animal Care Unit | And 8 more authors.
International Journal of Nanomedicine

The expectations of nanoparticle (NP)-based targeted drug delivery systems in cancer, when compared with convectional therapeutic methods, are greater efficacy and reduced drug side effects due to specific cellular-level interactions. However, there are conficting literature reports on enhanced tumor accumulation of targeted NPs, which is essential for translating their applications as improved drug-delivery systems and contrast agents in cancer imaging. In this study, we characterized biodegradable NPs conjugated with an anti-CD20 antibody for in vivo imaging and drug delivery onto tumor cells. NPs’ binding specificity mediated by anti-CD20 antibody was evaluated on MEC1 cells and chronic lymphocytic leukemia patients’ cells. The whole-body distribution of untargeted NPs and anti-CD20 NPs were compared by time-domain optical imaging in a localized human/mouse model of B-cell malignancy. These studies provided evidence that NPs’ functionalization by an anti-CD20 antibody improves tumor pharmacoki-netic profiles in vivo after systemic administration and increases in vivo imaging of tumor mass compared to non-targeted NPs. Together, drug delivery and imaging probe represents a promising theranostics tool for targeting B-cell malignancies. © 2015 Capolla et al. Source

Zuniga-Toala A.,National Autonomous University of Mexico | Zatarain-Barron Z.L.,National Institute of Medical science and Nutrition Salvador Zubiran | Hernandez-Pando R.,National Institute of Medical science and Nutrition Salvador Zubiran | Negrette-Guzman M.,National Autonomous University of Mexico | And 4 more authors.

It has been shown that the pretreatment with nordihydroguaiaretic acid (NDGA), a lignan with direct and indirect antioxidant properties, protects against the ischemia-reperfusion (I/R)-induced renal oxidant damage. Although it has been shown that NDGA induces Nrf2 nuclear translocation in renal epithelial LLC-PK1 cells in culture, it is unknown if NDGA may induce Nrf2 translocation in vivo. In this work was explored if NDGA is able to induce in vivo Nrf2 nuclear translocation in kidneys of rats submitted to uni-nephrectomy (U-NX) or I/R injury. Four groups of male Wistar rats were used: U-NX, NDGA, I/R, and I/R + NDGA. NDGA was injected i.p. (10 mg/kg/day) starting 48 h before I/R. Kidney samples were obtained at 3 h of reperfusion after to measure Nrf2 translocation. Additional groups of rats were studied at 24 h of reperfusion to measure histological damage and apoptosis. NDGA was able to induce Nrf2 translocation in vivo in kidneys of rats submitted to both U-NX and I/R injury and to protect against renal histological damage and apoptosis. It is concluded that the pretreatment of NDGA is able to induce in vivo nuclear Nrf2 translocation in kidney of rats suggesting that this may be involved in the renoprotection against I/R. © 2013 Elsevier GmbH. Source

Brunelli R.L.,Mind and Behavior Unit | Brunelli R.L.,Animal Behavior Graduate Group | Blake J.,Animal Care Unit | Willits N.,University of California at Davis | And 2 more authors.
Journal of the American Association for Laboratory Animal Science

Nursery-reared infants have several behavioral and physiologic differences from their mother-reared counterparts. We investigated whether a response-contingent surrogate mitigated some of those differences by decreasing fearfulness and partner-clinging and increasing environmental exploration in nursery-reared infants continuously paired with a peer. Six nursery-reared infant rhesus macaques (in pairs) were given a mechanical responsive surrogate (RS), and 6 (in pairs) were given an identical but nonresponsive surrogate (NRS). The 2 treatment groups were compared and then combined into a single group of all 12 of surrogate-exposed animals (CS) that was compared with a nonsurrogate control group (NS) of 10 nursery-reared infants. Results showed significant differences between CS and NS infants but no significant differences between the RS and NRS infants. As compared with NS infants, CS infants showed less partner-clinging, less affiliation directed toward only partner, and more foraging and tactile-oral exploration of the environment. These advantageous effects support additional research to develop improved surrogate and the implementation of surrogate programs for nursery-reared infants. Copyright 2014 by the American Association for Laboratory Animal Science Source

Grignaschi G.,Animal Care Unit | Zennaro E.,Animal Care Unit
Animal Technology and Welfare

The purpose of this investigation was to determine possible effects on breeding performance of different mice cleaning procedures carried out every 14 days in two Individually Ventilated Caging (IVC) systems. Trios of C57BI/6JOlaHsd mice were housed in two different IVC systems, both operated in positive mode but with a different cage ventilation design and number of air changes per hour (ACH): 50 vs 70. Three groups of cages per system were defined in terms of cleaning procedures as follows: Group 1 - complete cage change Group 2 - cage-bottom and bedding change Group 3 - bedding change only Breeding performances of mating trios were studied over a period of 26 weeks. Group 1 from both systems were comparable in terms of Production Efficiency Index (P.E.I) and other parameters related to litter size at birth and weaning, whereas Group 2 and 3 of the 50 ACH scored a lower, significant, P.E.I (Group 3, -17,8%; Group 2, -11,1%) vs the respective 70 ACH. In addition, the total mean number of pups weaned per female in the same 50 ACH group was significantly lower. There was a clear impact in the 50 ACH system vs the 70 ACH on breeding performance when only the bedding change was used procedurally for cage cleaning. One main difference between the two IVC systems that may, potentially, be responsible for the negative performance in the 50 ACH system is related to the different air injection point: low rear at animal level in the 50 ACH, compared to high rear in the 70 ACH system. Source

Granadillo M.,Center for Genetic Engineering and Biotechnology | Vallespi M.G.,Center for Genetic Engineering and Biotechnology | Batte A.,Center for Genetic Engineering and Biotechnology | Mendoza O.,Animal Care Unit | And 3 more authors.

The ultimate success of cancer vaccination is dependent upon the generation of tumor-specific CTLs. In this study, we designed and evaluated a novel fusion protein comprising a cell penetrating and immunostimulatory peptide corresponding to residues 32-51 of the Limulus polyphemus protein (LALF32-51) linked to human papillomavirus (HPV) 16 E7 antigen (LALF32-51-E7). We demonstrated that LALF32-51 penetrates the cell membrane and delivers E7 into cells. In a preclinical model of HPV16-induced cervical carcinoma we showed that vaccination with adjuvant-free LALF32-51-E7 fusion protein significantly improves the presentation of E7-derived peptides to T-cells in vitro and induces suppression of tumor growth. © 2010 Elsevier Ltd. Source

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