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Metastasizing, Luciferase Transduced MAT‑Lu Rat Prostate Cancer Models: Follow up of Bolus and Metronomic Therapy with Doxorubicin as Model Drug.

Jantscheff P, Esser N, Geipel A, Woias P, Ziroli V, Goldschmidtboing F, Massing U - Cancers (Basel) (2011)

Bottom Line: Our sensitive method, however, for the first time detects metastasis also in lymph node (11/24), spleen (3/24), kidney (4/24), liver (5/24), and bone tissue (femur or spinal cord - 5/20 and 12/20, respectively).Intravenous bolus treatment of MAT-Lu PCa with doxorubicin reduced subcutaneous tumor growth by about 50% and the number of animals affected by metastatic lesions in lymph nodes (0/4), lung (3/6) or lumbar spine (0/2), as determined by in vivo imaging and in vitro analysis.Additionally, the possible applicability of the luciferase transduced MAT-Lu model(s) to study basic principles of metronomic therapies via jugular vein catheter, using newly established active microport pumping systems, is presented.

View Article: PubMed Central - PubMed

Affiliation: Tumour Biology Center, Clinical Research, Department Lipids & Liposomes, Breisacher Str.117, D-79106 Freiburg, Germany. jantscheff@tumorbio.uni-freiburg.de.

ABSTRACT
The most fatal outcomes of prostate carcinoma (PCa) result from hormone-refractory variants of the tumor, especially from metastatic spread rather than from primary tumor burden. The goal of the study was to establish and apply rat MAT-Lu prostate cancer tumor models for improved non-invasive live follow up of tumor growth and metastasis by in vivo bioluminescence. We established luciferase transduced MAT-Lu rat PCa cells and studied tumor growth and metastatic processes in an ectopic as well as orthotopic setting. An intravenous bolus treatment with doxorubicin was used to demonstrate the basic applicability of in vivo imaging to follow up therapeutic intervention in these models. In vitro analysis of tissue homogenates confirmed major metastatic spread of subcutaneous tumors into the lung. Our sensitive method, however, for the first time detects metastasis also in lymph node (11/24), spleen (3/24), kidney (4/24), liver (5/24), and bone tissue (femur or spinal cord - 5/20 and 12/20, respectively). Preliminary data of orthotopic implantation (three animals) showed metastatic invasion to investigated organs in all animals but with varying preference (e.g., to lymph nodes). Intravenous bolus treatment of MAT-Lu PCa with doxorubicin reduced subcutaneous tumor growth by about 50% and the number of animals affected by metastatic lesions in lymph nodes (0/4), lung (3/6) or lumbar spine (0/2), as determined by in vivo imaging and in vitro analysis. Additionally, the possible applicability of the luciferase transduced MAT-Lu model(s) to study basic principles of metronomic therapies via jugular vein catheter, using newly established active microport pumping systems, is presented.

No MeSH data available.


Related in: MedlinePlus

Growth curve of orthotopic MAT-Lu PCa determined by luciferase in vivo imaging and tumor images from orthotopic MAT-Lu PCa. (Above) Tumor growth follow up by in vivo bioluminescence image-analysis once a week in a Nightowl LB981 camera system (Berthold, Bad-Wildbach, Germany). Growth was terminated at day 27 due to general health situation. (Below) Inverted images of in vivo bioluminescence from three individual rats at different imaging time points (days 10 and 28).
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f3-cancers-03-02679: Growth curve of orthotopic MAT-Lu PCa determined by luciferase in vivo imaging and tumor images from orthotopic MAT-Lu PCa. (Above) Tumor growth follow up by in vivo bioluminescence image-analysis once a week in a Nightowl LB981 camera system (Berthold, Bad-Wildbach, Germany). Growth was terminated at day 27 due to general health situation. (Below) Inverted images of in vivo bioluminescence from three individual rats at different imaging time points (days 10 and 28).

Mentions: To determine the growth of orthotopic rat MAT-Lu ELN PCa, we implanted the cells intraprostatic into three animals as a preliminary experiment, and followed up tumor increase by in vivo imaging once a week. As seen in Figure 3, tumor growth could be detected for the first time by bioluminescence seven days after implantation, while first imaging (day 2) did not show any identifiable signals. The tumor growth showed similar characteristics to the ectopic situation with weak growth during the first phase (until day 14) followed by striking exponential growth (until termination day 27). Final tumor dimensions at this time point were 4.33 ± 1.31 × 3.49 ± 0.91 cm (corresponding to a volume of 21.8 ± 5.1 cm3 and about 10% of the weight of the rat). The consistence of the orthotopic MAT-Lu tumors was similar to subcutaneous ones (see above) and also of rather cystic structure (not shown). No body weight reduction was observed (data not shown).


Metastasizing, Luciferase Transduced MAT‑Lu Rat Prostate Cancer Models: Follow up of Bolus and Metronomic Therapy with Doxorubicin as Model Drug.

Jantscheff P, Esser N, Geipel A, Woias P, Ziroli V, Goldschmidtboing F, Massing U - Cancers (Basel) (2011)

Growth curve of orthotopic MAT-Lu PCa determined by luciferase in vivo imaging and tumor images from orthotopic MAT-Lu PCa. (Above) Tumor growth follow up by in vivo bioluminescence image-analysis once a week in a Nightowl LB981 camera system (Berthold, Bad-Wildbach, Germany). Growth was terminated at day 27 due to general health situation. (Below) Inverted images of in vivo bioluminescence from three individual rats at different imaging time points (days 10 and 28).
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC3757437&req=5

f3-cancers-03-02679: Growth curve of orthotopic MAT-Lu PCa determined by luciferase in vivo imaging and tumor images from orthotopic MAT-Lu PCa. (Above) Tumor growth follow up by in vivo bioluminescence image-analysis once a week in a Nightowl LB981 camera system (Berthold, Bad-Wildbach, Germany). Growth was terminated at day 27 due to general health situation. (Below) Inverted images of in vivo bioluminescence from three individual rats at different imaging time points (days 10 and 28).
Mentions: To determine the growth of orthotopic rat MAT-Lu ELN PCa, we implanted the cells intraprostatic into three animals as a preliminary experiment, and followed up tumor increase by in vivo imaging once a week. As seen in Figure 3, tumor growth could be detected for the first time by bioluminescence seven days after implantation, while first imaging (day 2) did not show any identifiable signals. The tumor growth showed similar characteristics to the ectopic situation with weak growth during the first phase (until day 14) followed by striking exponential growth (until termination day 27). Final tumor dimensions at this time point were 4.33 ± 1.31 × 3.49 ± 0.91 cm (corresponding to a volume of 21.8 ± 5.1 cm3 and about 10% of the weight of the rat). The consistence of the orthotopic MAT-Lu tumors was similar to subcutaneous ones (see above) and also of rather cystic structure (not shown). No body weight reduction was observed (data not shown).

Bottom Line: Our sensitive method, however, for the first time detects metastasis also in lymph node (11/24), spleen (3/24), kidney (4/24), liver (5/24), and bone tissue (femur or spinal cord - 5/20 and 12/20, respectively).Intravenous bolus treatment of MAT-Lu PCa with doxorubicin reduced subcutaneous tumor growth by about 50% and the number of animals affected by metastatic lesions in lymph nodes (0/4), lung (3/6) or lumbar spine (0/2), as determined by in vivo imaging and in vitro analysis.Additionally, the possible applicability of the luciferase transduced MAT-Lu model(s) to study basic principles of metronomic therapies via jugular vein catheter, using newly established active microport pumping systems, is presented.

View Article: PubMed Central - PubMed

Affiliation: Tumour Biology Center, Clinical Research, Department Lipids & Liposomes, Breisacher Str.117, D-79106 Freiburg, Germany. jantscheff@tumorbio.uni-freiburg.de.

ABSTRACT
The most fatal outcomes of prostate carcinoma (PCa) result from hormone-refractory variants of the tumor, especially from metastatic spread rather than from primary tumor burden. The goal of the study was to establish and apply rat MAT-Lu prostate cancer tumor models for improved non-invasive live follow up of tumor growth and metastasis by in vivo bioluminescence. We established luciferase transduced MAT-Lu rat PCa cells and studied tumor growth and metastatic processes in an ectopic as well as orthotopic setting. An intravenous bolus treatment with doxorubicin was used to demonstrate the basic applicability of in vivo imaging to follow up therapeutic intervention in these models. In vitro analysis of tissue homogenates confirmed major metastatic spread of subcutaneous tumors into the lung. Our sensitive method, however, for the first time detects metastasis also in lymph node (11/24), spleen (3/24), kidney (4/24), liver (5/24), and bone tissue (femur or spinal cord - 5/20 and 12/20, respectively). Preliminary data of orthotopic implantation (three animals) showed metastatic invasion to investigated organs in all animals but with varying preference (e.g., to lymph nodes). Intravenous bolus treatment of MAT-Lu PCa with doxorubicin reduced subcutaneous tumor growth by about 50% and the number of animals affected by metastatic lesions in lymph nodes (0/4), lung (3/6) or lumbar spine (0/2), as determined by in vivo imaging and in vitro analysis. Additionally, the possible applicability of the luciferase transduced MAT-Lu model(s) to study basic principles of metronomic therapies via jugular vein catheter, using newly established active microport pumping systems, is presented.

No MeSH data available.


Related in: MedlinePlus