Primary lung neoplasms are represented by solid, solitary or multiple formations. Blisters are pulmonary emphysemas larger than 1cm, present complete destruction of lung tissue, resulting from dilation, destruction and coalescence of adjacent alveoli, filled with air, located in the subpleural space, surrounded by connective tissue septa, between the lung and the layer of the visceral pleura. Bullaes occupy more than 30% and surgical removal is recommended. The present clinical case reports a 14-year-old female dog, of mixed breed, with an increase in the coughs frequency, fatigue and exercise intolerance. A chest X-ray was taken, a large emphysematous cystic area was found, with thickened and irregular walls located in the left caudal pulmonary lobe, which measured 8cm x 7.5cm x 3cm, and rejected the bronchial branch corresponding to the left caudal pulmonary lobe, in addition to thickening of the bronchial walls, compatible with bronchopathy. The tomographic examination of the cavity showed an air content structure, oval to round in shape, with irregular thick hyperattenuating walls measuring approximately 0.4 cm in thickness, occupying more than 30% of the left hemithorax, and pulmonary lobectomy was chosen. Histopathology confirmed the diagnosis of bronchoalveolar adenocarcinoma, with the presence of sparse areas of necrosis and dystrophic calcification. Concluding that the tomographic exam is of great importance, because only through it, it is possible to evaluate if there is lymph node or pleural involvement or the presence of small metastasis foci. There is indication for surgery and histopathological examination of the piece for a definitive diagnosis.

Nude mice are the usual animal model for studying orthotopically implanted human tumors, and ultrasound imaging has emerged as a viable method for measuring tumors implanted orthotopically. The aim of this study was to evaluate ultrasound findings of liver tumors implanted into mice using a 13-MHz transducer and to correlate these findings with gross pathology and histological examinations. Tumor samples from liver metastases were obtained surgically from patients, and 1-mm³ fragments were implanted into the liver parenchyma of 38 nude mice. Mice were imaged monthly by ultrasound until sacrifice. Of the 38 mice implanted with tumor fragments, 11 developed tumors. Ultrasound detected nodular lesions in the 11 macroscopically positive animals and was able to identify the features of the engrafted tumors. Ultrasound imaging is a viable and noninvasive method for evaluating the liver parenchyma of nude mice, and showed 100% sensitivity and specificity in detecting and characterizing lesions.

The occurrence of liver metastasis is the major cause of death in colorectal cancer patients. The treatment consists of surgery and chemotherapy. However, the patient outcome is very unfavorable. Thus, the development of new therapeutic regimens to treat this condition is urgent and demand the establishment of good animal models. Among the models that have being used, the patient-derived xenografts (PDX) have emerged as one of the most promising. PDXs are preclinical models that faithfully represent the individuality of human cancer, by grafting fresh human tumor in severely immunodeficient mice which allows for higher tumor implantation rates and growth. Metastatic disease could be also modeled using orthotopic implantation into the affected organ. The patient-derived orthotopic xenografts (PDOX) can be interrogated for different treatment strategies based on the individualized gene signature of the human tumor, and the results can inform clinically relevant treatment strategies for the patient. With the objective to establish a PDOX from metastatic colorectal tumors in athymic nude mice, we implanted fresh tumor fragments into mouse liver parenchyma and propagated tumors from three patients which could be serially implanted in second and third mice generations. The morphological and immunohistochemical characterization indicate that xenografts recapitulate the tumor architecture and the expression of mismatch repair genes (MLH1, MSH2, MSH1, PMS2). After tumor implantation in first passage, the time of tumor growth decrease from 150-250 days to 30-100 days without loss of tumor identity. The growth of a post-transplantation lymphoproliferative disease (PTLD) was observed in one case. This pilot study was successful to establish the institutional PDX preclinical platform to study new therapeutic strategies, biomarkers of disease progression and treatment responsiveness. Citation Format: Tiago Goss dos Santos, Bruno Roque, Caroline Roque, Maria Dirlei Begnani, Eduardo Lima, Felipe Coimbra, Rubens Chojniak. Development of patient derived orthotopic xenografts from metastatic colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1045.