Imaging of bioluminescent LNCaP‐luc‐M6 Tumors: A new animal model for the study of metastatic human prostate cancer

Scatena, Caroline D.; Hepner, Mischa A; Oei, Yoko; Dusich, Joan; Yu, Shang‐Fan; Purchio, Tony; Contag, Pamela R.; Jenkins, Darlene E.

doi:10.1002/pros.20003

Cited by 66 publications

(51 citation statements)

References 34 publications

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“…The establishment and growth of tumors were monitored by bioluminescent imaging with the IVIS imaging system (Xenogen Corp., Alameda, CA) according to a protocol similar to those described. [45][46][47][48] Briefly, mice were administered firefly luciferin through intraperitoneal injection (100 L/mouse). Approximately 5 minutes later, while under isoflurane anesthesia, mice were imaged with a highly sensitive, cooled charged-coupled device camera in the light-tight specimen chamber of the IVIS system.…”

Section: Reagentsmentioning

confidence: 99%

Efficacy of a novel histone deacetylase inhibitor in murine models of hepatocellular carcinoma

Kashida

Kulp

et al. 2007

Hepatology

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H epatocellular carcinoma (HCC) is the fifth most common human cancer and third most frequent cause of cancer death worldwide. 1 Although over 80% of new HCC cases will occur in Eastern Asia and subSaharan Africa, 2 the startling increase in HCC incidence in the United States over the past 20-25 years and the typically high mortality from this disease have established HCC as an important health concern in this country. [2][3][4][5][6] The clinical management of HCC is complicated by typically late-stage disease at presentation and prevalent underlying liver dysfunction that can render patients ineligible for potentially curative surgical therapies, which are generally suitable for only 20%-30% of HCC patients. 3,5,7 Although regional therapies, such as transarterial embolization and percutaneous treatments, are used in patients with nonresectable disease, their success is curtailed by recurrence as locally advanced or metastatic disease. For these patients, systemic therapy is indicated but has been largely unsuccessful. 3,4,[8][9][10] Thus, a clear need exists to develop effective, life-prolonging therapeutic strategies for the large number of HCC patients with advanced disease.A major challenge in the systemic treatment of HCC is cellular resistance to conventional cytotoxic agents, which, at

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Section: Reagentsmentioning

confidence: 99%

Efficacy of a novel histone deacetylase inhibitor in murine models of hepatocellular carcinoma

Kashida

Kulp

et al. 2007

Hepatology

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“…Inefficient cell uptake of D-luciferin due to alterations in tumour blood supply and cell membrane permeability decreases the luciferase activity. Scatena et al [43] also observed constant bioluminescent signals in prostate tumours despite the 3.3-fold increase in tumour volume. This indicates that luciferase expression can be lost in time, probably owing to genomic instability.…”

Section: Discussionmentioning

confidence: 88%

Functional imaging of multidrug resistance in an orthotopic model of osteosarcoma using 99mTc-sestamibi

Welling

Que

Henriquez

et al. 2007

Eur J Nucl Med Mol Imaging

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Purpose The purpose of this work was the development of an orthotopic model of osteosarcoma based on luciferaseexpressing tumour cells for the in vivo imaging of multidrug resistance (MDR) with 99m Tc-sestamibi. Methods Doxorubicin-sensitive (143B-luc + ) and resistant (MNNG/HOS-luc + ) osteosarcoma cell lines expressing different levels of P-glycoprotein and carrying a luciferase reporter gene were inoculated into the tibia of nude mice. Local tumour growth was monitored weekly by bioluminescence imaging and X-ray. After tumour growth, a 99m Tcsestamibi dynamic study was performed. A subset of animals was pre-treated with an MDR inhibitor (PSC833). Images were analysed for calculation of 99m Tc-sestamibi washout half-life (t 1/2 ), percentage washout rate (%WR) and tumour/non-tumour (T/NT) ratio.Results A progressively increasing bioluminescent signal was detected in the proximal tibia after 2 weeks. The t 1/2 of 99m Tc-sestamibi was significantly shorter (p<0.05) in drugresistant MNNG/HOS-luc + tumours (t 1/2 =87.3±15.7 min) than in drug-sensitive 143B-luc + tumours (t 1/2 =161.0±47.4 min) and decreased significantly with PSC833 (t 1/2 =173.0± 24.5 min, p<0.05). No significant effects of PSC833 were observed in 143B-luc + tumours. The T/NT ratio was significantly lower (p<0.05) in MNNG/HOS-luc + tumours than in 143B-luc + tumours at early (1.55±0.22 vs 2.14± 0.36) and delayed times (1.12±0.11 vs 1.62±0.33). PSC833 had no significant effects on the T/NT ratios of either tumour. Conclusion The orthotopic injection of tumour cells provides an animal model suitable for functional imaging of MDR. In vivo bioluminescence imaging allows the non-invasive monitoring of tumour growth. The kinetic analysis of 99m Tc-sestamibi washout provides information on the functional activity of MDR related to P-glycoprotein expression and its pharmacological inhibition in osteosarcoma.

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“…Docetaxel (Taxotere, Henry Schein) was prepared according to the manufacturer's instructions. Luciferaseexpressing COLO205 cells were stably transfected to constitutively express luciferase (28 ; 2577, dilution 1:200) were ordered from Cell Signaling. Anti-Chk1 antibody was purchased from Santa Cruz Biotechnology (Santa Cruz, CA, G-4).…”

Section: Methodsmentioning

confidence: 99%

PF-00477736 Mediates Checkpoint Kinase 1 Signaling Pathway and Potentiates Docetaxel-Induced Efficacy in Xenografts

Zhang¹,

Yan²,

Painter³

et al. 2009

Clinical Cancer Research

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Purpose: Checkpoint kinase 1 (Chk1) plays a critical role in the activation of mitotic spindle checkpoint and DNA damage checkpoint. We examined the preclinical use of the Chk1 inhibitor PF-00477736 as a docetaxel-sensitizing agent. Specifically, we investigated the correlation between PF-00477736^mediated modulation of biomarkers and the sensitization of docetaxel efficacy. Experimental Design: In vitro and in vivo studies using COLO205 and other cell lines were done to assess PF-00477736^induced enhancement of docetaxel efficacy and effects on associated biomarkers. Conclusions: Docetaxel triggers mitotic spindle checkpoint activation at low concentrations and activates both the DNA damage checkpoint and the spindle checkpoint at high concentrations. In combination with docetaxel, PF-00477736 abrogates the mitotic checkpoint, as well as the DNA damage checkpoint, and results in sensitization to docetaxel. Chk1inhibitor PF-00477736 offers a therapeutic potential for the enhancement of taxane therapy.

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Imaging of bioluminescent LNCaP‐luc‐M6 Tumors: A new animal model for the study of metastatic human prostate cancer

Abstract: The LNCaP-luc-M6 cell line is a bioluminescent, hormone-sensitive prostate cancer cell line applicable for BLI studies to non-invasively monitor subcutaneous and orthotopic prostate tumor growth and metastasis in vivo.

Cited by 66 publications

References 34 publications

Efficacy of a novel histone deacetylase inhibitor in murine models of hepatocellular carcinoma

Efficacy of a novel histone deacetylase inhibitor in murine models of hepatocellular carcinoma

Functional imaging of multidrug resistance in an orthotopic model of osteosarcoma using 99mTc-sestamibi

PF-00477736 Mediates Checkpoint Kinase 1 Signaling Pathway and Potentiates Docetaxel-Induced Efficacy in Xenografts

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