P-glycoprotein expression in cartilaginous tumors

Rosier, Randy N.; O’Keefe, Regis J.; Teot, Lisa A.; Fox, Edward J.; Nester, Theresa; Puzas, J. Edward; Reynolds, Paul; Hicks, David G.

doi:10.1002/(sici)1096-9098(199706)65:2<95::aid-jso5>3.0.co;2-i

Cited by 26 publications

(11 citation statements)

References 42 publications

(51 reference statements)

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“…6 Our results show that Runx2/Cbfa1 is expressed constitutively in all 11 pathology specimens of human osteosarcoma. Of note, a chondroblastic osteosarcoma showed the highest Runx2/Cbfa1 immunoreactivity (fig 1).…”

Section: Resultsmentioning

confidence: 60%

“…To ascertain sample immunoreactivity, specimens were stained with anti-collagen I antibody (Santa Cruz Biotechnology; Santa Cruz, California, USA) by indirect immunohistochemistry with avidinbiotin peroxidase, as described previously. 6 Eleven specimens were found to be immunoreactive and subsequently stained with Runx2/Cbfa1 and NFkB (p65) specific antibodies (Santa Cruz). Immunoreactive specimens were reviewed and graded by an orthopaedic oncologist (RNR) using a previously established grading system.…”

Section: Methodsmentioning

confidence: 99%

“…Immunoreactive specimens were reviewed and graded by an orthopaedic oncologist (RNR) using a previously established grading system. 6 A Pearson correlation analysis between Runx2/Cbfa1 and NFkB (p65) scores was established.…”

Section: Methodsmentioning

confidence: 99%

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An immunohistochemical analysis to evaluate an inverse correlation between Runx2/Cbfa1 and NFκB in human osteosarcoma

Andela

Siddiqui²,

Groman³

et al. 2005

J Clin Pathol

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Background: Dominant negative inhibition of nuclear factor kB (NFkB) signalling activity in a human osteosarcoma cell line (Saos2) results in malignant reversion and the induction of the osteoblast differentiating transcription factor, Runx2/ Cbfa1. This observation suggests that there is an inverse relation between a transcription factor associated with malignant progression and chemoresistance (NFkB) and an osteoblast differentiating transcription factor (Runx2/Cbfa1). Aims: To assess and correlate Runx2/Cbfa1 and NFkB (p65) immunoreactivity in human osteosarcoma. Methods: Runx2/Cbfa1 and NFkB (p65) immunoreactivity was assessed on 11 paraffin wax embedded archival specimens of human primary osteosarcoma by standard immunohistochemical methods and scored on a scale of 0-3. A Pearson correlation analysis between Runx2/Cbfa1 and NFkB (p65) scores was established. Results: Runx2/Cbfa1 was expressed constitutively in all pathology specimens of human osteosarcoma. Of note, a chondroblastic osteosarcoma showed the highest Runx2/ Cbfa1 immunoreactivity. A Pearson correlation did not support an inverse correlation between Runx2/Cbfa1 and NFkB (p65) scores (r = 0.57) in human osteosarcoma. Conclusion: Runx2/Cbfa1 immunoreactivity does not inversely correlate with NFkB immunoreactivity, and thus cannot serve as an indirect measure of NFkB activity or an independent predictive or prognostic indicator. O steosarcoma is the most common primary bone malignancy, with a propensity for pulmonary metastasis and a predilection for paediatric and geriatric age groups. The cornerstone of current clinical management involves high dose neoadjuvant chemotherapy, to which 40-60% of cases are non-responsive. Thus, prognosticating, stratifying, and individualising treatment is crucial for optimal and cost effective management. 1 ''Although the NFkB activation status of a tumour has predictive and prognostic value, it cannot be measured by routine laboratory investigations'' Histopathologically, osteosarcomas are characterised by atypical cells (osteoblasts, mesenchymal cells, fibroblasts, and chondrocytes) enmeshed in a disorganised bony matrix (immature osteoid). We recently showed that dominant negative inhibition of the promalignant transcription factor, nuclear factor kB (NFkB), in a human osteosarcoma cell line (Saos2) results in malignant reversion and the induction of the osteoblast differentiating transcription factor, Runx2/ Cbfa1.2 3 This finding was interesting for two reasons:N It validated the concept that cellular differentiation and transformation are mutually exclusive processes.N It suggested an inverse relation between a transcription factor associated with malignant progression 4 and chemoresistance (NFkB) 5 and an osteoblast differentiating transcription factor (Runx2/Cbfa1).Although the NFkB activation status of a tumour has predictive and prognostic value, it cannot be measured by routine laboratory investigations. Our present study was designed to assess whether Runx2/Cbfa1 expression could serve as an indirect me...

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Section: Resultsmentioning

confidence: 60%

Section: Methodsmentioning

confidence: 99%

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An immunohistochemical analysis to evaluate an inverse correlation between Runx2/Cbfa1 and NFκB in human osteosarcoma

Andela

Siddiqui²,

Groman³

et al. 2005

J Clin Pathol

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“…on the enhanced permeation and retention (EPR) phenomenon [47,50] including to overcome multi-drug resistance [51] via local sustained release [52], but without emphasis on the optimal size range or design for biocompatibility in the biological system in the physiologic state, until recently [1][2][3]7,8,25,26]. However, it has since then been realized that more attention must be paid to the biophysical properties of macromolecular therapeutics such as the purposeful introduction of cationicity to the exterior of sub-optimally sized nanoparticles in order to improve their permeation across the blood-tumor barrier and diffusion through the tumor interstitium [53,54], which results in significant non-selective toxicity to the biological system in the physiologic state [2,3,25,26].…”

Section: Reviewmentioning

confidence: 99%

Translational theranostic methodology for diagnostic imaging and the concomitant treatment of malignant solid tumors

Sarin

2015

Neurovascular Imaging

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Pathologic hyperpermeability exists in the spectrum of disease states, including neuro-ischemic, neuro-inflammatory and neuro-oncological. To-date the characterization of disease pathology with T 1 -weighted quantitative dynamic contrast-enhanced magnetic resonance imaging has relied on the study of modeled microvascular parameters such as diseased tissue transvascular flow rates of small molecule paramagnetic imaging agents with short plasma half-lives, based on which it is difficult to assess the specific nature of the disease state. Another type of T 1 -weighted quantitative dynamic contrast-enhanced magnetic resonance imaging involves the use of paramagnetic heavy metal-chelated dendrimer nanoparticles that possess longer plasma half-lives with pre-determined molar relaxivities to quantitatively image concentration of macromolecular contrast agent accumulation over time in hyperpermeable pathology such as solid tumor tissue with the important advantage of concomitantly treating the pathology, which, in recent years, has been shown to be possible with the use of optimally-sized theranostic dendrimer nanoparticles in the 7 to 10 nanometer size range that are functionalized biocompatibly with a small molecule therapeutic. In this focused review, this translational theranostic methodology for quantitative dynamic contrast-enhanced magnetic resonance imaging and the concomitant treatment of malignant solid tumors with optimally designed theranostic nanoparticles within the 7 to 10 nanometer size range is discussed in context of fine-tuning its suitability for the study and treatment of other disease states with pathologic hyperpermeability and without.

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“…It is also expressed in the hypertrophic region of the epiphyseal growth plate, providing additional evidence for its important physiologic excretory rolein protecting the cell from extracellular insults [8]. …”

Section: The Expression Of P-glycoprotein Allows Chondrosarcoma Cementioning

confidence: 99%

Surmounting Chemotherapy and Radioresistance in Chondrosarcoma: Molecular Mechanisms and Therapeutic Targets

Onishi

Hincker

Lee

2011

Sarcoma

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Chondrosarcoma, a primary malignancy of bone, has eluded successful treatment with modern chemotherapeutic and radiation regimens. To date, surgical resection of these tumors remains the only curative treatment offered to patients with this diagnosis. Understanding and exploring the nature of chemotherapy and radiation resistance in chondrosarcoma could lead to new molecular targets and more directed therapy for these notoriously difficult-to-treat tumors. Here we review the most current hypotheses regarding the molecular mechanisms mediating chemotherapy and radiation resistance and the future direction of chondrosarcoma therapy research.

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P-glycoprotein expression in cartilaginous tumors

Cited by 26 publications

References 42 publications

An immunohistochemical analysis to evaluate an inverse correlation between Runx2/Cbfa1 and NFκB in human osteosarcoma

An immunohistochemical analysis to evaluate an inverse correlation between Runx2/Cbfa1 and NFκB in human osteosarcoma

Translational theranostic methodology for diagnostic imaging and the concomitant treatment of malignant solid tumors

Surmounting Chemotherapy and Radioresistance in Chondrosarcoma: Molecular Mechanisms and Therapeutic Targets

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