On the current management of osteosarcoma. A critical evaluation and a proposal for a modified treatment strategy

Bruland, Øyvind S.; Pihl, Alexander

doi:10.1016/s0959-8049(97)00252-9

Cited by 126 publications

(100 citation statements)

References 52 publications

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“…Doxorubicin is one of the most effective drugs in the management of osteosarcoma (Bruland and Pihl, 1997;Ferguson and Goorin, 2001). Although liposomal delivery of doxorubicin improves the tumour uptake compared to free doxorubicin, the drug distribution within the tumour tissue is still heterogeneous (Vaage et al, 1997;Davies et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

Hyaluronidase induces a transcapillary pressure gradient and improves the distribution and uptake of liposomal doxorubicin (Caelyx™) in human osteosarcoma xenografts

et al. 2005

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Liposomal drug delivery enhances the tumour selective localisation and may improve the uptake compared to free drug. However, the drug distribution within the tumour tissue may still be heterogeneous. Degradation of the extracellular matrix is assumed to improve the uptake and penetration of drugs. The effect of the ECM-degrading enzyme hyaluronidase on interstitial fluid pressure and microvascular pressure were measured in human osteosarcoma xenografts by the wick-in-needle and micropipette technique, respectively. The tumour uptake and distribution of liposomal doxorubicin were studied on tumour sections by confocal laser scanning microscopy. The drugs were injected i.v. 1 h after the hyaluronidase pretreatment. Intratumoral injection of hyaluronidase reduced interstitial fluid pressure in a nonlinear dose-dependent manner. Maximum interstitial fluid pressure reduction of approximately 50% was found after injection of 1500 U hyaluronidase. Neither intratumoral nor i.v. injection of hyaluronidase induced any changes in the microvascular pressure. Thus, hyaluronidase induced a transcapillary pressure gradient, resulting in a four-fold increase in the tumour uptake and improving the distribution of the liposomal doxorubicin. Hyaluronidase reduces a major barrier for drug delivery by inducing a transcapillary pressure gradient, and administration of hyaluronidase adjuvant with liposomal doxorubicin may thus improve the therapeutic outcome.

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Section: Discussionmentioning

confidence: 99%

Hyaluronidase induces a transcapillary pressure gradient and improves the distribution and uptake of liposomal doxorubicin (Caelyx™) in human osteosarcoma xenografts

et al. 2005

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“…Most published studies on osteosarcoma and Ewing's sarcoma apply patient selection on the basis of age, tumour site, stage or treatment protocol, and are thus not representative of OS and ES in general [13]. In order to address a more general development in the treatment and outcome of high-grade bone sarcomas we therefore present an unselected patient material of OS and ES from a single national reference institution, with analyses of general trends over time across all ages, stages and tumour sites, and with sub analyses where appropriate.…”

Section: Discussionmentioning

confidence: 99%

“…This finding supports the view that no major chemotherapy breakthrough can explain the entire improvement in survival seen over time, and the fraction of patients treated with chemotherapy has remained virtually unchanged (Table II). The international experience is that although major improvements were seen in both OS and ES after the introduction of effective combination chemotherapy in the late 1970s and early 1980s, subsequent further intensification has led to only limited progress [6,13,15]. It should also be noted that there is no evidence in the literature of the natural prognosis of OS and ES having changed over the time period in question.…”

Section: Discussionmentioning

confidence: 99%

Management of high-grade bone sarcomas over two decades: The Norwegian Radium Hospital experience

et al. 2006

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“…4 OS is characterized by a high propensity for metastasis, mostly to the lungs, with 10-20% having detectable metastases at diagnosis. 5 Only B10% of OS patients achieve long-term disease-free interval. 6 The unifying histologic features of OS are the presence of malignant osteoid produced by neoplastic cells.…”

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confidence: 99%

Osteogenic BMPs promote tumor growth of human osteosarcomas that harbor differentiation defects

Luο

Chen

Song

et al. 2008

Laboratory Investigation

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Osteosarcoma (OS) is the most common primary malignancy of bone. Here, we investigated a possible role of defective osteoblast differentiation in OS tumorigenesis. We found that basal levels of the early osteogenic marker alkaline phosphatase (ALP) activity were low in OS lines. Osteogenic regulators Runx2 and OSX, and the late marker osteopontin (OPN) expressed at low levels in most OS lines, indicating that most OS cells fail to undergo terminal differentiation. Furthermore, OS cells were refractory to osteogenic BMP-induced increases in ALP activity. Osteogenic BMPs were shown to upregulate early target genes, but not late osteogenic markers OPN and osteocalcin (OC). Furthermore, osteogenic BMPs failed to induce bone formation from human OS cells, rather effectively promoted OS tumor growth in an orthotopic OS model. Exogenous expression of early target genes enhanced BMP-stimulated OS tumor growth, whereas osteogenic BMP-promoted OS tumor growth was inhibited by exogenous Runx2 expression. These results suggest that alterations in osteoprogenitors may disrupt osteogenic differentiation pathway. Thus, identifying potential differentiation defects in OS tumors would allow us to reconstruct the tumorigenic events in osteoprogenitors and to develop rational differentiation therapies for clinical OS management.

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On the current management of osteosarcoma. A critical evaluation and a proposal for a modified treatment strategy

Cited by 126 publications

References 52 publications

Hyaluronidase induces a transcapillary pressure gradient and improves the distribution and uptake of liposomal doxorubicin (Caelyx™) in human osteosarcoma xenografts

Hyaluronidase induces a transcapillary pressure gradient and improves the distribution and uptake of liposomal doxorubicin (Caelyx™) in human osteosarcoma xenografts

Management of high-grade bone sarcomas over two decades: The Norwegian Radium Hospital experience

Osteogenic BMPs promote tumor growth of human osteosarcomas that harbor differentiation defects

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