Growth of human bronchial carcinomas in nude mice

Abstract

Summary Two hundred and thirteen lung tumours of primary site and 42 metastases were heterotransplanted into nude mice with an overall success rate of 44%. There were differences in success between the histological types. Squamous cell and adenocarcinoma had the highest success rate (51% and 43%, respectively) whereas large cell and small cell carcinoma had a lower success rate (38% for both). The average volume doubling times in the first passage in nude mice ranged from 8.2 in large cell carcinomas to 18.9 days in adenocarcinomas. In subsequent passages an increase in growth rate was found, the overall average doubling time falling from 14.5 days in the first passage to 7.1 days in the second passage. In a study with 171 non-small cell lung carcinomas (NSCLC), the growth data in nude mice were correlated with the clinical data of the corresponding patients. A relationship between the growth parameters in nude mice and prognosis of patients could not be found.During the past 3 years we have transplanted in the course of cooperative clinical studies 255 human lung tumours into nude mice. In this report we describe the incidence and rate of growth of these tumours in the nude mouse, as primary transplants and passaged tumours, and further we examined whether the growth characteristics of these tumours might be of clinical prognostic value. Comparison of a part of the presented data with other measurements and the clinical course will be published elsewhere. Materials and methodsNude mice Athymic nude NMRI-mice (own breeding or Zentralinstitut fur Versuchstierzucht, Hannover), female, 6-9 weeks old, were kept under standardized conventional conditions (Makrolon cages, 270C room temperature, 50% relative humidity, autoclaved bedding) in a separated room especially controlled against infections. An autoclaved special diet (altromin 1410, Altromin Spezialfutterwerke, D-4937 Lage) and acidified water (pH 2-3) were given ad libitum. Patients and tumoursTwo hundred and fifty five histologically verified lung tumours and their lymph node metastases from 213 patients were xenografted into nude mice.

Human tumor xenografts as model for drug testing

“…In most cases the tumors initially exhibit an exponential growth, followed by a slowing of the growth rate (Fig. 1) [80], which, during the first passage, can range from a few days to more than 2 months [82]. Similar volume doubling times have also been reported for other histological types of xenografts [34,104].…”

Patient-Derived First Generation Xenografts of Non–Small Cell Lung Cancers: Promising Tools for Predicting Drug Responses for Personalized Chemotherapy

“…The high engraftment rate (90%) obtained by subrenal capsule grafting allowed the survival of the various types of NSCLC examined. The high take rate contrasts with the much lower rates (20-40%) reported for subcutaneous graft models (13)(14)(15)(16)(17) and is likely a result of superior nutrient supply and enhancement of graft microvascularity provided by the subrenal capsule site (18)(19)(20)(21)(22)(23)(24). The high engraftment rate was further ensured by rigorous selection of viable tumor tissue through fluorescence illumination and by identifying such tissue in cryostat sections from randomly selected pregraft fragments.…”

“…As an alternative approach, chemosensitivity of patients' cancers to various regimens can be evaluated using transplantable subcutaneous tumor lines developed from resected cancer specimens. Although such tumor lines are valuable for drug development and may lead to useful predictions (9)(10)(11)(12), the engraftment rate of s.c. implanted cancers is low (20-40%) and establishing transplantable tumor lines may take as long as 10 months (13)(14)(15)(16)(17), severely limiting the usefulness of this approach for personalized chemotherapy.…”

Molecular heterogeneity of non-small cell lung carcinoma patient-derived xenografts closely reflect their primary tumors

“…We and others have reported the establishment of transplantable NSCLC tumors directly from patients to immune‐deficient mice. These PDXs bear close histopathological resemblance to their corresponding primary cancers and they recapitulate patient responses to a number of therapeutic agents . However, it is still unclear to what extent they fully recapitulate the genetic, epigenetic, and signaling mechanisms that collectively drive clinical disease, especially for their matched patient tumors.…”