Modelo de tumor de pulmão em rato com o carcinossarcoma de Walker

Abstract

OBJETIVO: Desenvolver um modelo de tumor pulmonar em ratos com o carcinossarcoma de Walker e verificar in vivo a presença de tumor por meio de tomografia computadorizada (TC). MÉTODOS: Ratos Wistar fêmeas (n=47) foram anestesiados com pentobarbital, intubados por traqueostomia e submetidos a toracotomia para injeção no parênquima pulmonar de células do tumor de Walker ou do veículo das mesmas. O estudo consistiu de duas etapas: na primeira desenvolveu-se a técnica de implante do tumor e estabeleceu-se o número de células necessário para um bom índice de pega tumoral. Na segunda etapa, determinou-se o volume do tumor em cm³ (Dxd²/2) através de TC e necropsia (6° dia do implante), e analizou-se a sobrevida dos animais. RESULTADOS: O índice de pega do tumor foi 93,3%, sendo 81,8% na primeira etapa e 100% na segunda. A mortalidade cirúrgica foi 17,0%. As medidas dos tumores foram semelhantes (0,099 vs. 0,111 cm³) na tomografia e na necropsia, respectivamente (r=0,993; p<0,0001) e a sobrevida mediana foi 10 dias. CONCLUSÃO: O alto índice de pega e a boa correlação dos dados de tomografia com os de necropsia permitem, por meio deste modelo, o monitoramento tomográfico do crescimento tumoral e, portanto, a avaliação da ação in vivo de drogas anti-tumorais, além da análise de sobrevida sem a necessidade do sacrifício dos animais.

Experimental rat lung tumor model with intrabronchial tumor cell implantation

“…This is similar to the tumor take rate (94.5%) observed for an earlier model developed in our laboratory 10 and inoculated via thoracotomy with 2 x 10 5 cells of the same lineage. In a study by Wang et al 9 , tumor cells implanted by direct puncture of the parenchyma via thoracotomy yielded a higher take rate (100%) than cells inoculated intrabronchially (95%), illustrating the influence of the microenvironment upon tumor development.…”

“…Models based on implantation via thoracotomy may present high tumor take rates, but require a high level of surgical skill, are more difficult to reproduce and are associated with higher rates of surgical mortality. The thoracotomy-based model developed by Gomes-Neto et al 10 presented a relatively high surgical mortality rate (14.3%), in contrast with the present model of intrabronchial implantation (4.8%). The aggressive nature of Walker's carcinosarcoma is evident in the high tumor take rates observed and the rapid growth of the neoplasm characterized by the presence of large nodules in the lung (average volume: 0.118 ± 0.108 cm 3 ) as early as the 5th day following cell implantation.…”

“…The neoplasm is cultivated at the laboratory by weekly intramuscular injections with a suspension of 10 6 tumor cells in the inner thigh of Wistar rats. The cells were prepared for the present study as described in the literature 10 . Tumor cell viability was assessed with trypan blue staining and the number of cells per 1 ml of suspension was determined using a Neubauer chamber.…”

“…Moreover, orthotopic lung tumor models using human cancer cells require the use of cell lineages from primary lung tumors as well as immunosuppressed animals, since this type of tumor will not take or grow in immunocompetent animals 8 . In lung tumor models cells may be inoculated intrabronchially in the pulmonary parenchyma 7,8 or may be implanted directly by puncture during open thoracotomy 9,10 .The orthotopic lung tumor model using intrabronchial inoculation of tumor cells was originally developed by McLemore et al 11 and involved inserting a catheter by tracheal puncture. Later Howard et al 8 and Johnston et al 7 improved the technique by using cervical tracheotomy for the insertion of an ultrafine intrabronchial catheter, thus making it possible to implant cells on the periphery of the pulmonary parenchyma.…”

“…Later Howard et al 8 and Johnston et al 7 improved the technique by using cervical tracheotomy for the insertion of an ultrafine intrabronchial catheter, thus making it possible to implant cells on the periphery of the pulmonary parenchyma. None of the studies above used computed tomography (CT) to detect the presence of lung tumors in the animals, although a few other and more recent experimental studies have reported using CT scans with small animals 10,12,13 . The objectives of this study were a) to develop a technically simple rat lung tumor model with intrabronchial implantation of cells of Walker's carcinosarcoma by cervical tracheotomy, and b) to diagnose tumors in vivo using high-resolution computed tomography (HRCT) with subsequent correlation of findings from necropsy and histopathological examination.…”