Increased intratumoral fluorothymidine uptake levels following multikinase inhibitor sorafenib treatment in a human renal cell carcinoma xenograft model

Murakami, Masahiro; Zhao, Yan; Yu, Wenwen; Fatema, Chowdhury Nusrat; Nishijima, Ken‐ichi; Yamasaki, Masahiro; Takiguchi, Mitsuyoshi; Tamaki, Nagara; Kuge, Yuji

doi:10.3892/ol.2013.1459

Cited by 10 publications

(13 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The remaining 3 groups were treated with CDDP (10 mg/kg body weight), SOX (80 mg/kg body weight), or CDDP plus SOX (5 and 40 mg/kg body weight, respectively) intraperitoneally on alternative days for 3 weeks. The doses were selected based on previously conducted experiments (22,23). tumor volume was measured before the treatment injections were administered and on the 7th, 14th and 21st day of treatment.…”

Section: Methodsmentioning

confidence: 99%

Synergistic growth inhibition by sorafenib and cisplatin in human osteosarcoma cells

et al. 2015

View full text Add to dashboard Cite

Abstract. Molecular-targeted therapy has shown promise as a treatment for advanced osteosarcoma (OS). Sorafenib (SOR), a multikinase inhibitor, is the approved systemic drug of choice for OS, but has demonstrated limited benefits due to its toxicity and other adverse effects. Therapy strategies for reducing toxicity include using lower doses of SOR in combination with other complementary agents. Cisplatin (CDDP) has been shown to be a promising anticancer drug against various types of cancer including OS. In the present study, SOR was combined with CDDP to determine whether this combinatorial treatment suppressed tumor growth thereby simultaneously reducing doses of the two drugs for the treatment of OS. Human Saos-2 OS cells were treated with SOR and CDDP, alone and in combination, and the effect of these treatments on cell proliferation, colony formation, cell cycle, apoptosis, migration, and invasion, and involvement in receptor signaling, as well as tumor growth ability in nude mice was determined. It was found that the combination of low concentrations of SOR and CDDP significantly suppressed the cell proliferation, colony formation, migration and invasion, and induced cell apoptosis and cell cycle arrest in the G0/G1 stage, and suppressed tumor growth in a nude mouse model compared to the actions of either agent alone. The results also showed that SOR in combination with CDDP significantly suppressed the phosphorylation of extracellular signal-regulated kinase (ERK), which may contribute to the inhibition of tumor growth. These results suggested that SOR in combination with CDDP acts synergistically in the treatment of OS.

show abstract

Section: Methodsmentioning

confidence: 99%

Synergistic growth inhibition by sorafenib and cisplatin in human osteosarcoma cells

et al. 2015

View full text Add to dashboard Cite

show abstract

“…Sorafenib is a multikinase inhibitor that has anti-proliferative and anti-angiogenic activities and is reported to show significant therapeutic effects against RCC [5, 6]. Contrary to our expectation, however, the level of [ 3 H]FLT in the tumor significantly increased after the sorafenib treatment [4]. …”

Section: Introductionmentioning

confidence: 72%

“…; Nexavar, Bayer Pharmaceuticals Corporation, West Haven, CT, USA) once daily for 3 days. The vehicle was administered to the control group [4]. …”

Section: Methodsmentioning

confidence: 99%

“…Positron emission tomography (PET) using 3′-[ 18 F]fluoro-3′-deoxythymidine ([ 18 F]FLT) is one of the noninvasive methods of assessing tumor proliferation [1–3]. Accordingly, we have recently evaluated the tumor responses to sorafenib treatment in our model experiments using a renal cell carcinoma (RCC) xenograft and [methyl- 3 H(N)]-3′-fluoro-3′-deoxythythymidine ([ 3 H]FLT) [4]. Sorafenib is a multikinase inhibitor that has anti-proliferative and anti-angiogenic activities and is reported to show significant therapeutic effects against RCC [5, 6].…”

Section: Introductionmentioning

confidence: 99%

“…Including in our previous study [4], static parameters such as standardized uptake value (SUV) have been extensively used to monitor treatment-induced changes in oncology [7–10]. PET is, however, a dynamic imaging modality that allows the imaging and observation of the distribution of a radiolabeled tracer throughout the body over time [11–15].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Dynamic PET evaluation of elevated FLT level after sorafenib treatment in mice bearing human renal cell carcinoma xenograft

Ukon

Shimizu

et al. 2016

EJNMMI Res

Self Cite

View full text Add to dashboard Cite

BackgroundSorafenib, an oral multikinase inhibitor, has anti-proliferative and anti-angiogenic activities and is therapeutically effective against renal cell carcinoma (RCC). Recently, we have evaluated the tumor responses to sorafenib treatment in a RCC xenograft using [Methyl-3H(N)]-3′-fluoro-3′-deoxythythymidine ([3H]FLT). Contrary to our expectation, the FLT level in the tumor significantly increased after the treatment. In this study, to clarify the reason for the elevated FLT level, dynamic 3′-[18F]fluoro-3′-deoxythymidine ([18F]FLT) positron emission tomography (PET) and kinetic studies were performed in mice bearing a RCC xenograft (A498).The A498 xenograft was established in nude mice, and the mice were assigned to the control (n = 5) and treatment (n = 5) groups. The mice in the treatment group were orally given sorafenib (20 mg/kg/day p.o.) once daily for 3 days. Twenty-four hours after the treatment, dynamic [18F]FLT PET was performed by small-animal PET. Three-dimensional regions of interest (ROIs) were manually defined for the tumors. A three-compartment model fitting was carried out to estimate four rate constants using the time activity curve (TAC) in the tumor and the blood clearance rate of [18F]FLT.ResultsThe dynamic pattern of [18F]FLT levels in the tumor significantly changed after the treatment. The rate constant of [18F]FLT phosphorylation (k3) was significantly higher in the treatment group (0.111 ± 0.027 [1/min]) than in the control group (0.082 ± 0.009 [1/min]). No significant changes were observed in the distribution volume, the ratio of [18F]FLT forward transport (K1) to reverse transport (k2), between the two groups (0.556 ± 0.073 and 0.641 ± 0.052 [mL/g] in the control group).ConclusionsOur dynamic PET studies indicated that the increase in FLT level may be caused by the phosphorylation of FLT in the tumor after the sorafenib treatment in the mice bearing a RCC xenograft. Dynamic PET studies with kinetic modeling could provide improved understanding of the biochemical processes involved in tumor responses to therapy.

show abstract

A rapid ex vivo tissue model for optimising drug detection and ionisation in MALDI imaging studies

Huber

Aichler

Sun

et al. 2014

Histochem Cell Biol

View full text Add to dashboard Cite

The aim of this study was to establish an ex vivo model for a faster optimisation of sample preparation procedures, for example matrix choice, in matrix-assisted laser desorption/ionisation (MALDI) drug imaging studies. The ionisation properties of four drugs, afatinib, erlotinib, irinotecan and pirfenidone, were determined in an ex vivo tissue experiment by spotting decreasing dilution series onto liver sections. Hereby, the drug signals were distinctly detectable using different matrix compounds, which allowed the selection of the optimal matrix for each drug. The analysis of afatinib and erlotinib yielded high drug signals with α-cyano-4-hydroxycinnamic acid matrix, whereas 2,3-dihydroxybenzoic acid was identified as optimal matrix for irinotecan and pirfenidone detection. Our method was validated by a MALDI drug imaging approach of in vivo treated mouse tissue resulting in corresponding findings, indicating the spotting method as an appropriate approach to determine the matrix of choice. The present study shows the accordance between the detection of ex vivo spotted drugs and in vivo administered drugs by MALDI-TOF and MALDI-FT-ICR imaging, which has not been demonstrated so far. Our data suggest the ex vivo tissue spotting method as an easy and reliable model to optimise MALDI imaging measurements and to predict drug detection in tissue sections derived from treated mice prior to the recruitment of laboratory animals, which helps to save animals, time and costs.

show abstract

Increased intratumoral fluorothymidine uptake levels following multikinase inhibitor sorafenib treatment in a human renal cell carcinoma xenograft model

Cited by 10 publications

References 23 publications

Synergistic growth inhibition by sorafenib and cisplatin in human osteosarcoma cells

Synergistic growth inhibition by sorafenib and cisplatin in human osteosarcoma cells

Dynamic PET evaluation of elevated FLT level after sorafenib treatment in mice bearing human renal cell carcinoma xenograft

A rapid ex vivo tissue model for optimising drug detection and ionisation in MALDI imaging studies

Contact Info

Product

Resources

About