Analysis of Tumor Vessel Supply in Lewis Lung Carcinoma in Mice by Fluorescent Microsphere Distribution and Imaging with Micro- and Flat-Panel Computed Tomography

Savai, Rajkumar; Wolf, Joachim C.; Greschus, Susanne; Eul, Bastian; Schermuly, Ralph Theo; Hänze, Jörg; Voswinckel, Robert; Langheinrich, Alexander C.; Traupe, Horst; Seeger, Werner; Rose, Frank

doi:10.1016/s0002-9440(10)61184-4

Cited by 32 publications

(31 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In this regard, an earlier study of our group has shown that the pulmonary artery plays a major role in delivering blood supply to LLC1 lung tumors. 2 This finding is in accordance with the observation that jugular vein catheter injection of PEI-complexed siRNA is particularly appropriate for targeting of lung tumor tissue through the pulmonary artery. The finding that LLC1 lung cancer tissue was transfected by siRNA with a higher efficiency than healthy lung tissue is most likely because of anatomical and functional changes to the tumor vessels.…”

Section: Discussionsupporting

confidence: 89%

“…2 In this model, we demonstrated that tumor vascularization arises primarily from the pulmonary artery. This model has now been employed to compare different routes of in vivo siRNA administration for targeting lung tumors.…”

Section: Introductionmentioning

confidence: 80%

“…2 The experiments were started 6-10 days later. Subcutaneous LLC1 tumor model: Tumorigenicity was assessed by subcutaneous injection of LLC1 cells (5 Â 10 6 cells per 200 ml saline) into mice.…”

Section: Tumor Modelsmentioning

confidence: 99%

See 2 more Smart Citations

Intravenous injection of siRNA directed against hypoxia-inducible factors prolongs survival in a Lewis lung carcinoma cancer model

Kamlah

Eul

et al. 2008

Cancer Gene Ther

View full text Add to dashboard Cite

Different routes for the in vivo administration of synthetic siRNA complexes targeting lung tumors were compared, and siRNA complexes were administered for the inhibition of hypoxia-inducible factor (HIF-1a and HIF-2a). Intravenous jugular vein injection of siRNA proved to be the most effective means of targeting lung tumor tissue in the Lewis lung carcinoma (LLC1) model. In comparison, intraperitoneal injection of siRNA was not suitable for targeting of lung tumor and intratracheal administration of siRNA exclusively targeted macrophages. Inhibition of HIF-1a and HIF-2a by siRNA injected intravenously was validated by immunohistofluorescent analysis for glucose-transporter-1 (GLUT-1), a well-established HIF target protein. The GLUT-1 signal was strongly attenuated in the lung tumors of mice treated with siRNA-targeting HIF-1a and HIF-2a, compared with mice treated with control siRNA. Interestingly, injection of siRNA directed against HIF-1a and HIF-2a into LLC1 lung tumor-bearing mice resulted in prolonged survival. Immunohistological analysis of the lung tumors from mice treated with siRNA directed against HIF-1a and HIF2a displayed reduced proliferation, angiogenesis and apoptosis, cellular responses, which are known to be affected by HIF. In conclusion, intravenous jugular vein injection of siRNA strongly targets the lung tumor and is effective in gene inhibition as demonstrated for HIF-1a and HIF-2a.

show abstract

Section: Discussionsupporting

confidence: 89%

Section: Introductionmentioning

confidence: 80%

See 1 more Smart Citation

Intravenous injection of siRNA directed against hypoxia-inducible factors prolongs survival in a Lewis lung carcinoma cancer model

Kamlah

Eul

et al. 2008

Cancer Gene Ther

View full text Add to dashboard Cite

show abstract

“…The total length of the canula from needle point to the end of canula was 28 mm. A longer canula can puncture the outer surface of the lung parenchyma, while a shorter canula will result in instillation in the higher regions of the lung, similar to what Savai et al 13 reported. High instillation of the tumour cells makes accurate discrimination of the tumour from other dense tissues such as the heart with CT more complicated.…”

Section: Preparation Of the Canulasupporting

confidence: 76%

Validation of intratracheal instillation of lung tumour cells in mice using single photon emission computed tomography/computed tomography imaging

Buckle

Leeuwen

2010

Lab Anim

View full text Add to dashboard Cite

In search of better predictive animal models for evaluating treatment response in lung cancer, orthotopic lung tumour models are a great step forward over traditional subcutaneous models. Crucial in the development of such orthotopic models is a reliable and reproducible instillation method. Because cells are instilled inside the thorax, the accuracy of the instillation and visualization of tumour growth demands the use of non-invasive imaging methods. We used a minimally invasive intratracheal intubation method to instill bioluminescent lung tumour cells in the lung parenchyma. Adaptation of the cell containing medium provides the possibility of tracing the exact location of the injection by means of single photon emission computed tomography/computed tomography (CT) imaging. The transplantation medium was also optimized to prevent migration of the injected substance. This results in the outgrowth of single and well-defined lung tumours at the instillation site. Finally, tumour growth was validated and longitudinally monitored with a combination of CT and bioluminescence imaging. The reported transplantation procedure enables the assessment of injection accuracy and provides a good approach for the generation of orthotopic lung tumour models for future response imaging studies.

show abstract

“…Lewis lung carcinoma (LLC) was isolated from the epidermoid carcinoma of the lung in mice. It is regarded as an essential tumor model in studies of metastasis (4,5), vessel formation (6), and effects of therapy (7). A tumor-bearing model of mice with LLC exhibits a greater metastatic potential than a tumor-bearing model alone (8,9).…”

Section: Introductionmentioning

confidence: 99%

Vascular endothelial growth factor-A and changes in a tumor-bearing mouse model with Lewis lung cancer

et al. 2011

View full text Add to dashboard Cite

Abstract. Vascular endothelial growth factor-A (VEGF-A)affects tumor growth and metastasis through stimulation of angiogenesis. The purpose of this study was to describe features of Lewis lung cancer (LLC) in mice and compare the serum VEGF-A levels with those of normal control mice. Two groups of mice were compared: one was subcutaneously injected with LLC cells (n=16) and the other served as the normal control (n=6). The serum VEGF-A levels were measured by ELISA prior to inoculation, and at 7, 21 and 35 days post-inoculation. The tumor weight and the metastatic condition were evaluated on day 35. Changes in body weight and serum VEGF-A concentration over a period of time were compared between the groups using generalized estimating equations. The relationship between the primary tumor and the metastatic condition was analyzed using the Spearman's rank correlation test. The survival rate was 56.3% on day 35 post-tumor inoculation. No difference was found between the groups with regard to gastrocnemius muscle weight on day 35 post-inoculation [0.1315±0.0066 g vs. 0.1308±0.0069 g (normal control)]. In tumor-bearing mice, the weight gain at sacrifice was less (0.24±0.45 vs. 1.93±0.47 g, P= 0.01), the final mean tumor volume and weight were 4264.69±1038.32 mm 3 and 3.70±0.83 g, the number of nodules in the lungs and livers was 6.33 (range 0-20) and 2.22 (range 0-11), respectively, and the serum VEGF-A levels were significantly higher than those of control mice. In conclusion, lower body weight gain, metastasis in the liver and lungs, and elevated VEGF-A levels are features of LLC in mice.

show abstract

Analysis of Tumor Vessel Supply in Lewis Lung Carcinoma in Mice by Fluorescent Microsphere Distribution and Imaging with Micro- and Flat-Panel Computed Tomography

Cited by 32 publications

References 25 publications

Intravenous injection of siRNA directed against hypoxia-inducible factors prolongs survival in a Lewis lung carcinoma cancer model

Intravenous injection of siRNA directed against hypoxia-inducible factors prolongs survival in a Lewis lung carcinoma cancer model

Validation of intratracheal instillation of lung tumour cells in mice using single photon emission computed tomography/computed tomography imaging

Vascular endothelial growth factor-A and changes in a tumor-bearing mouse model with Lewis lung cancer

Contact Info

Product

Resources

About