RESUMO
Brain metastasis (BM) represents a clinical challenge for patients with advanced HER2 + breast cancer (BC). The monoclonal anti-HER2 antibody trastuzumab (TZ) improves survival of BC patients, but it has low central nervous system penetrance, being ineffective in treating BM. Previous studies showed that ferritin nanoparticles (HFn) may cross the blood brain barrier (BBB) through binding to the transferrin receptor 1 (TfR1). However, whether this has efficacy in promoting the trans-BBB delivery of TZ and combating BC BM was not studied yet. Here, we investigated the potential of HFn to drive TZ brain delivery and promote a targeted antitumor response in a murine model of BC BM established by stereotaxic injection of engineered BC cells overexpressing human HER2. HFn were covalently conjugated with TZ to obtain a nanoconjugate endowed with HER2 and TfR1 targeting specificity (H-TZ). H-TZ efficiently achieved TZ brain delivery upon intraperitoneal injection and triggered stable targeting of cancer cells. Treatment with H-TZ plus docetaxel significantly reduced tumor growth and shaped a protective brain microenvironment by engaging macrophage activation toward cancer cells. H-TZ-based treatment also avoided TZ-associated cardiotoxicity by preventing drug accumulation in the heart and did not induce any other major side effects when combined with docetaxel. These results provided in vivo demonstration of the pharmacological potential of H-TZ, able to tackle BC BM in combination with docetaxel. Indeed, upon systemic administration, the nanoconjugate guides TZ brain accumulation, reduces BM growth and limits side effects in off-target organs, thus showing promise for the management of HER2 + BC metastatic to the brain.
RESUMO
Respiratory diseases significantly affect intensive pig farming, causing production losses and increased antimicrobial use. Accurate classification of lung lesions is crucial for effective diagnostics and disease management. The integration of non-destructive and rapid techniques would be beneficial to enhance overall efficiency in addressing these challenges. This study investigates the potential of near-infrared (NIR) spectroscopy in classifying pig lung tissues. The NIR spectra (908-1676 nm) of 101 lungs from weaned pigs were analyzed using a portable instrument and subjected to multivariate analysis. Two distinct discriminant models were developed to differentiate normal (N), congested (C), and pathological (P) lung tissues, as well as catarrhal bronchopneumonia (CBP), fibrinous pleuropneumonia (FPP), and interstitial pneumonia (IP) patterns. Overall, the model tailored for discriminating among pathological lesions demonstrated superior classification performances. Major challenges arose in categorizing C lungs, which exhibited a misclassification rate of 30% with N and P tissues, and FPP samples, with 30% incorrectly recognized as CBP samples. Conversely, IP and CBP lungs were all identified with accuracy, precision, and sensitivity higher than 90%. In conclusion, this study provides a promising proof of concept for using NIR spectroscopy to recognize and categorize pig lungs with different pathological lesions, offering prospects for efficient diagnostic strategies.
RESUMO
Respiratory diseases significantly affect intensive pig finishing farms, causing production losses and increased antimicrobial use (AMU). Lesion scoring at slaughter has been recognized as a beneficial practice to evaluate herd management. The integrated analysis of abattoir lesion scores and AMU data could improve decision-making by providing feedback to veterinarians and farmers on the effectiveness of antimicrobial treatments, thus rationalizing their use. This study compared lung and pleural lesion scores collected at Italian pig slaughterhouses with on-farm AMU, estimated through a treatment index per 100 days (TI100). Overall, 24,752 pig carcasses, belonging to 236 batches from 113 finishing farms, were inspected. Bronchopneumonia and chronic pleuritis were detected in 55% and 48% of the examined pigs, respectively. Antimicrobials were administered in 97% of the farms during the six months prior to slaughter (median TI100 = 5.2), notwithstanding compliance with the mandatory withdrawal period. EMA category B (critical) antimicrobials were administered in 15.2% of cases (median TI100 = 0.06). The lung score was not associated with the total AMU, but significant, positive associations were found with the past use of critical antimicrobials (p = 0.041) and macrolides (p = 0.044). This result highlights the potential of abattoir lung lesion monitoring to rationalize antimicrobial stewardship efforts, contributing to AMU reduction.