Monitoring and quantitative assessment of tumor burden using in vivo bioluminescence imaging

Author(s):  
Chia-Chi Chen ◽  
Jeng-Jong Hwang ◽  
Gann Ting ◽  
Yun-Long Tseng ◽  
Shyh-Jen Wang ◽  
...  
2004 ◽  
Vol 120 (2) ◽  
pp. 249-255 ◽  
Author(s):  
Shiva Sarraf-Yazdi ◽  
Jing Mi ◽  
Mark W. Dewhirst ◽  
Bryan M. Clary

Neoplasia ◽  
2000 ◽  
Vol 2 (6) ◽  
pp. 491-495 ◽  
Author(s):  
Alnawaz Rehemtulla ◽  
Lauren D. Stegman ◽  
Shaun J. Cardozo ◽  
Sheila Gupta ◽  
Daniel E. Hall ◽  
...  

Blood ◽  
2009 ◽  
Vol 113 (16) ◽  
pp. 3765-3772 ◽  
Author(s):  
David Daydé ◽  
David Ternant ◽  
Marc Ohresser ◽  
Stéphanie Lerondel ◽  
Sabrina Pesnel ◽  
...  

Abstract Clinical studies have shown a large interindividual variability in rituximab exposure and its significant influence on clinical response in patients receiving similar doses of antibody. The aim of this study was to evaluate the influence of tumor burden on dose-concentration-response relationships of rituximab. Murine lymphoma cells (EL4, 8 × 103), transduced with human CD20 cDNA and transfected with luciferase plasmid (EL4-huCD20-Luc), were intravenously injected into C57BL/6J mice. Tumor burden detection, dissemination, and progression were evaluated quantitatively by in vivo bioluminescence imaging. Different doses of rituximab (6, 12, 20, or 40 mg/kg) were infused 13 days after lymphoma cell inoculation, and rituximab serum concentrations were measured by enzyme-linked immunosorbent assay. Without rituximab, all mice developed disseminated lymphoma and died within 30 days, whereas a significant dose-response relationship was observed in mice receiving rituximab. The 20-mg/kg dose was adequate to study interindividual variability in response because 23% of mice were cured, 59% had partial response, and 18% had disease progression. Rituximab concentrations were inversely correlated with tumor burden; mice with low tumor burden had high rituximab concentrations. Furthermore, rituximab exposure influenced response and survival. Finally, using a pharmacokinetic-pharmacodynamic model, we demonstrated that tumor burden significantly influenced rituximab efficacy.


Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1110-1110
Author(s):  
Martin Chopra ◽  
Simone S Riedel ◽  
Viktoria von Krosigk ◽  
Carina A Bäuerlein ◽  
Christian Brede ◽  
...  

Abstract Abstract 1110 The cytokine tumor necrosis factor-α (TNF) has pleiotropic functions both in normal physiology and disease. TNF and its relative lymphotoxin-α (LT) signal by activating two cell surface receptors TNFR1 and TNFR2. TNFR1 is expressed on most cells whereas TNFR2 is mainly expressed in cells of the hematopoietic system. TNF-TNFR interactions were shown to play a major role in graft-versus-leukemia effect and in the immunosurveillance of solid tumors. To study the contribution of TNF-TNFR interactions on tumor cell progression we employed a syngenic B16 melanoma mouse model combined with in vivo bioluminescence imaging. Firefly luciferase-transgenic B16 melanoma cells were injected intravenously into syngenic albino C57BL/6 hosts. The host mice were either of wildtype, TNF, LT, TNFR1, TNFR2 knockout or TNFR1R2 double knockout genotype. The localization and expansion of the B16 cells was monitored by in vivo bioluminescence imaging for up to 14 days. On days 15, mice were sacrificed and internal organs were imaged ex vivo to further elucidate the organ-specific tumor burden. B16 tumors were primarily found in the lungs of all genotypes. All female knockout genotypes displayed a higher lung tumor burden than wildtype mice. In male mice, only TNF knockout presented enhanced tumor cell signals. Following ex vivo imaging we evaluated the pulmonary infiltration of NK1.1 or NKp46, CD8, CD4 and CD4/CD25/Foxp3 regulatory T cells by flow cytometry and immunofluorescence microscopy. Compared to wildtype mice, more regulatory T cells infiltrated the lungs of female TNFR1 knockout mice (200%). In LT knockout mice, very few NK cells (<20%) but more CD4+ cells (160%) infiltrated the lungs. Only subtle changes occurred in the other deficient mouse strains. However, these changes were independent of the presence of tumor cells and could also be found in normal knockout mice without B16 tumors. Within sections of tumor-bearing lungs, we found that TNF and all three TNFR knockouts exhibited less CD8+ cells within tumors than did wildtype or LT knockout mice. The number of CD8+ cells in normal lung tissue was not altered across the different genotypes. The deficit in NK cells of LT knockout mice was confirmed by histology. The enhanced tumor progression in all knockout mice could be a secondary effect due to their altered immune phenotype rather than to the loss of TNF-TNFR interactions. To circumvent this potential experimental bias and to further assess the influence of the loss of expression of parts of the TNF/TNFR-system in immune cells only, we generated bone marrow chimeras by reconstituting lethally irradiated female wildtype mice with bone marrow derived from TNF, LT, TNFR1 or TNFR2 knockout mice. Tumor cell signals in these chimeric mice progressed more than in normal wildtype mice. In contrast to the first set of experiments with knockout mice, we found that mice reconstituted with either TNF or TNFR2 knockout bone marrow presented less tumor cell signal than did mice reconstituted with wildtype bone marrow. TNF-TNFR interactions between immune cells appear to exhibit pro-tumorigenic functions in our mouse model. These results show that TNF-TNFR interactions are an important step in tumor cell progression and that the outcome of these interactions differs, depending on whether immune or parenchymal cells are deficient in TNF-TNFR signalling components. Disclosures: No relevant conflicts of interest to declare.


2020 ◽  
Vol 20 (9) ◽  
pp. 1147-1156
Author(s):  
Hanrui Li ◽  
GeTao Du ◽  
Lu Yang ◽  
Liaojun Pang ◽  
Yonghua Zhan

Background: Hepatocellular carcinoma is cancer with many new cases and the highest mortality rate. Chemotherapy is the most commonly used method for the clinical treatment of hepatocellular carcinoma. Natural products have become clinically important chemotherapeutic drugs due to their great potential for pharmacological development. Many sesquiterpene lactone compounds have been proven to have antitumor effects on hepatocellular carcinoma. Objective: Britanin is a sesquiterpene lactone compound that can be considered for the treatment of hepatocellular carcinoma. The present study aimed to investigate the antitumor effect of britanin. Methods: BEL 7402 and HepG2 cells were used to study the cytotoxicity and antitumor effects of britanin. Preliminary studies on the nuclear factor kappa B pathway were conducted by western blot analysis. A BEL 7402-luc subcutaneous tumor model was established for the in vivo antitumor studies of britanin. In vivo bioluminescence imaging was conducted to monitor changes in tumor size. Results: The results of the cytotoxicity analysis showed that the IC50 values for britanin in BEL 7402 and HepG2 cells were 2.702μM and 6.006μM, respectively. The results of the colony formation demonstrated that the number of cells in a colony was reduced significantly after britanin treatment. And the results of transwell migration assays showed that the migration ability of tumor cells was significantly weakened after treatment with britanin. Tumor size measurements and staining results showed that tumor size was inhibited after britanin treatment. The western blot analysis results showed the inhibition of p65 protein expression and reduced the ratio of Bcl-2/Bax after treatment. Conclusion: A series of in vitro and in vivo experiments demonstrated that britanin had good antitumor effects and provided an option for hepatocellular carcinoma treatment.


2006 ◽  
Vol 81 (10) ◽  
pp. 1421-1427 ◽  
Author(s):  
Xiaojuan Chen ◽  
Xiaomin Zhang ◽  
Courtney S. Larson ◽  
Marshall S. Baker ◽  
Dixon B. Kaufman

PLoS ONE ◽  
2015 ◽  
Vol 10 (3) ◽  
pp. e0120925 ◽  
Author(s):  
Binje Vick ◽  
Maja Rothenberg ◽  
Nadine Sandhöfer ◽  
Michela Carlet ◽  
Cornelia Finkenzeller ◽  
...  

2016 ◽  
Vol 258 ◽  
pp. S234
Author(s):  
S. Seyed Forootan ◽  
F. Mutter ◽  
J. Clarke ◽  
A. Kipar ◽  
K. Park ◽  
...  

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