The Clinical Approach Towards Chondrosarcoma

Gelderblom, Hans; Hogendoorn, Pancras C.W.; Dijkstra, Sander; Rijswijk, Carla Sp van; Krol, Augustinus D.G.; Taminiau, A. H. M.; Bovée, Judith V.M.G.

doi:10.1634/theoncologist.2007-0237erratum

Cited by 130 publications

(222 citation statements)

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“…Chondrosarcomas account for approximately 20% of bone malignancies, with conventional chondrosarcoma associated with a significant rate of morbidity and a 10-year survival rate of 29-83% [1,2]. Although surgical resection is the primary treatment option for patients with chondrosarcoma, conventional chemotherapy and radiotherapy are additional treatment options [2][3][4].…”

Section: Introductionmentioning

confidence: 99%

Recombinant human PDCD5 sensitizes chondrosarcomas to cisplatin chemotherapy in vitro and in vivo

Chen

Zhou

et al. 2010

Apoptosis

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Clinical management of chondrosarcoma remains a challenging problem, largely due to the toxicity and resistance of this tumor to conventional chemotherapy. Programmed Cell Death 5 (PDCD5) is a protein that accelerates apoptosis in different cell types in response to various stimuli, and has been shown to be down-regulated in many cancer tissues. In this study, mRNA and protein levels of PDCD5 were found to be up-regulated in cisplatin-treated SW1353 chondrosarcoma cells compared with untreated cells. Recombinant human PDCD5 (rhPDCD5) was also shown to sensitize chondrosarcoma cells to cisplatin-based chemotherapy, with inhibition of cell growth and apoptosis detected both in vitro and in vivo. Increased expression of Bax and decreased expression of Bcl-2 were also observed, along with release of cytochrome c from mitochondria into the cytosol. Additionally, cleavage of caspase-9 and caspase-3, as well as the cleavage of poly (ADP-ribose) polymerase (PARP), were detected, suggesting that sensitization of chondrosarcoma cells involves the intrinsic mitochondrial apoptosis pathway. In vivo, the treatment of a xenograft model of chondrosarcoma with rhPDCD5 and cisplatin significantly inhibited tumor cell proliferation and induced apoptosis compared to treatment with cisplatin alone. Overall, these data provide a theoretical basis for the administration of rhPDCD5 and cisplatin for the treatment of patients with chondrosarcoma.

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Section: Introductionmentioning

confidence: 99%

Recombinant human PDCD5 sensitizes chondrosarcomas to cisplatin chemotherapy in vitro and in vivo

Chen

Zhou

et al. 2010

Apoptosis

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“…S'agissant des six SO traités, le bénéfice clinique obtenu dans les trois cas de chondrosarcome, tumeur réputée chimiorésistante [5], est à souligner. Le temps jusqu'à progression y apparaît nettement augmenté par comparaison avec les lignes antérieures de chimiothérapie par méthotrexate à haute dose ou adriamycine et cisplatine notamment ( Tableau 3).…”

Section: Réponse Au Traitement Et Survieunclassified

“…Le temps jusqu'à progression y apparaît nettement augmenté par comparaison avec les lignes antérieures de chimiothérapie par méthotrexate à haute dose ou adriamycine et cisplatine notamment ( Tableau 3). Quelques rares cas analogues [4] ont été signalés, conduisant à des essais de phase II [5].…”

Section: Réponse Au Traitement Et Survieunclassified

Gemcitabine and docetaxel combination as rescue chemotherapy for sarcomas. A retrospective single-institution study of 14 patients

et al. 2011

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“…Since the tumour is made chemo-and radio-resistant by the poorly vascularized and chondrogenic nature of the tissue, the only therapeutic control of chondrosarcoma currently available is radical surgery [1][2][3]. Among the numerous strategies aimed at increasing intarget drug accumulation, "vectors" with high specific affinities for one or more targets offer one of the most promising therapeutic opportunities [4].…”

Section: Introductionmentioning

confidence: 99%

Quaternary ammonium-melphalan conjugate for anticancer therapy of chondrosarcoma: in vitro and in vivo preclinical studies

et al. 2011

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Cartilage tumours present ongoing therapeutic challenges due to their chondrogenic extracellular matrix that potentially hampers drug delivery, their low percentage of dividing cells, and their poor vascularity. In this context, and based on the affinity of the quaternary ammonium moiety for proteoglycans (PG), we developed a strategy that uses the quaternary ammonium function to selectively deliver DNA alkylating agents to the cartilage tumour tissue. We engineered the quaternary ammonium derivative of melphalan (Mel-AQ) and assessed its antitumoural activity in vitro and in vivo. In vitro, micromolar concentrations of Mel-AQ inhibited the proliferation of human HEMC-SS chondrosarcoma and Saos-2 osteosarcoma cell lines. Moreover, 24-h incubation with 20 μM Mel-AQ induced a 2.5-fold increase in S population and a 1.5-fold increase in subG0G1 population compared to controls. In vivo, Mel-AQ demonstrated antitumour activity in the orthotopic model of primary Swarm rat chondrosarcoma. When given to chondrosarcoma-bearing rats (three doses of 16 μmol/kg at days 8, 12 and 16 post-implant), Mel-AQ demonstrated an optimal antitumour effect at day 43, when tumour cell growth inhibition peaked at 69%. Interestingly, the treatment protocol was proved well tolerated, since the animals showed no weight loss over the course of the study. This antitumoural effect was assessed in vivo by scintigraphic imaging using (99m)Tc-NTP 15-5 developed in our lab as a PG-targeting radiotracer, and tumour tissue was analyzed at study-end by biochemical PG assay with Alcian blue staining. Mel-AQ treatment led to a significant decrease in the PG content of tumoural tissue. These experimental results highlighted the promising antitumour potential of Mel-AQ as a PG-targeting strategy for therapeutic management of chondrosarcoma.

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The Clinical Approach Towards Chondrosarcoma

Cited by 130 publications

References 0 publications

Recombinant human PDCD5 sensitizes chondrosarcomas to cisplatin chemotherapy in vitro and in vivo

Recombinant human PDCD5 sensitizes chondrosarcomas to cisplatin chemotherapy in vitro and in vivo

Gemcitabine and docetaxel combination as rescue chemotherapy for sarcomas. A retrospective single-institution study of 14 patients

Quaternary ammonium-melphalan conjugate for anticancer therapy of chondrosarcoma: in vitro and in vivo preclinical studies

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