Osteosarcoma, role

Recently, Choy et al. also reported that LDHs are an efficient drug reservoir for folate derivatives [187]. Folic acid derivatives, folinic acid and methotrexate (MTX), have been successfully hybridized with Mg/Al LDHs by ion-exchange reactions. Cellular uptake tests with the MTX-LDH hybrids were carried out in the fibroblast (human tendon) and osteosarcoma (SaOS-2) cell lines by in vitro assay. They found that the LDH not only plays a role as a biocompatible delivery matrix for drugs but also facilitates a significant increase in the delivery efficiency. 

Muller WA, Luz A, Schaffer EH, et al. 1983. The role of time-factor and RBE for the induction of osteosarcomas by incorporated short-lived bone-seekers. Health Phys44(Suppl 1) 203-212. 

The approach to PNET is similar to that described for osteosarcomas, although the chosen cytotoxic agents are different and radiotherapy plays a more important role. Treatment should be started with chemotherapy, usually comprising a combination of agents such as doxorubicin, VP-16, ifosfamide or cyclophosphamide, actinomycin-D and vincristine. After an optimal local response has been obtained, either surgery or local radiotherapy is applied depending on the site of the disease and the applicability of the technique. Sometimes a combination of both is applied. After optimal local treatment. 

Adjuvant chemotherapy involves the use of antineoplastic drugs when surgery or radiation therapy has eradicated the primary tumor but historical experience with similar patients indicates a high risk of relapse due to micrometastases. Adjuvant chemotherapy should employ drugs that are known to be effective in the treatment of advanced stages of the particular tumor being treated. Adjuvant chemotherapy has played a major role in the cure of several types of childhood cancers as well as breast cancer, colorectal cancer, and osteosarcoma in adults. 

Study of other rare hereditary cancers has led to the location of 20 or more additional probable tumor-suppressor genes. One of these, p53, is inactive in over 50% of all human cancers and over 90% of sqamous cell carcinomas of the skin.ee In small-cell lung cancers and osteosarcoma both RB and p53 are inactive.2 Protein p53 is a stronger tumor suppressor than protein Rb. Results of a variety of experiments have suggested that p53, a DNA-binding protein of known structure, plays a key role in checking DNA for damage at the C,... 

Very little work has been reported on the role of oxidative stress in osteoblasts. However, osteoblasts can be induced to produce intracellular ROS (Cortizo et al., 2000 Liu et al., 1999), which can cause a decrease in alkalinephosphatase (ALP) activity that is partially inhibited by vitamin E and cause cell death (Cortizo et al., 2000 Liu et al., 1999). Treatment of rat osteosarcoma ROS 17/2.8 cells with tumor necrosis factor-alpha (TNF-a) suppressed bone sialoprotein (BSP) gene transcription through a tyrosine kinase-dependent pathway that generates ROS (Samoto et al., 2002). H202 modulated intracellular calcium (Ca2+) activity in osteoblasts by increasing Ca2+ release from the intracellular Ca2+ stores (Nam et al., 2002). 

Cortizo, A.M., Bruzzone, L., Molinuevo, S., and Etcheverry, S.B. 2000. A possible role of oxidative stress in the vanadium-induced cytotoxicity in the MC3T3E1 osteoblast and UMR106 osteosarcoma cell lines. Toxicology 147, 89-99. 

Far fewer studies to date have looked at the role of LRP in clinical drug resistance. LRP has been shown to have prognostic significance in AML and epithelial ovarian cancer (23). In the latter study, LRP was an independent determinant of response to treatment and overall survival, whereas Pgp and MRP were not. LRP levels were also shown to be increased post-chemotherapy in osteosarcoma and this was a poor prognostic sign (27). LRP levels prior to chemotherapy did not show prognostic significance. 

Other general cellular responses to Mn(II) include a description by Budzik et al. [216] of Mn(II) participation in the action of Mullerian-inhibiting substance, and the role of Mn(II) in osteosarcoma cell attachment to fibrinogen and von Willebrand factor, mediated by the fibronectin, vitronectin, and adhesion receptors [217]. 

Clarke MF et al. (2006) Cancer stem cells perspectives on current status and future directions AACR Workshop on Cancer Stem Cells. Cancer Res 66(19) 9339-9344 Dincbas FO et al. (2005) The role of preoperative radiotherapy in nonmetastatic high-grade osteosarcoma of the extremities for limb-sparing surgery. Int J Radiat Oncol Biol Phys 62(3) 820-828... 

It is desirable to show how new platinum structures may differ in signalling pathways from those of cisplatin and oxaliplatin. An important example is the role of pS3, the tumor suppresor g te, in modulation of cytotoxicity of platinum drugs. BBR 3464 di lays high activity in human tumor cell lines characterized by both wild type and mutant pS3 gene (21). In contrast, on average, cells with mutant pS3 are more resistant to the effea of cisplatin (25). It has been hypothesized that sensitivity or resistance of tumor cells to cisplatin might be also associated widi the processes involving pS3 (26,27). Transfer of functional pS3 into p53-null SAOS osteosarcoma cells actually reduced cellular sensitivity... 

---