Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0279530 (bone cancer)
 1,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study aims to clarify the enhancement effect on chromosomal aberrations via selective energy absorption by Cu atoms in cultured bone cancer cells with non-labelled Cu-pyruvaldehyde-bis(N(4)-methylsemicarbazone) (Cu-PTSM) and monochromatic X rays. The X rays having the energy of the Cu K-shell absorption edge arising from synchrotron radiation (KEK-PF) was used as radiation source. Cu-PTSM labelled with copper radionuclides has been developed for medical imaging using positron emission tomography (PET). Evidence clearly showed that the absorption of X rays in the Cu K-shell caused this enhancement. After cells were treated with 1000 nM Cu-PTSM, the enhancement ratio of the initial yield of isochromatid breaks caused by CuK-H X-ray irradiation to that by 200 kV(p) X rays was approximately 2.8. About 5.6 times of the remaining isochromatid breaks were observed at 4 h in Cu-PTSM treated samples irradiated with CuK-H X rays comparing to that with 200 kV(p) X rays. In this study, uniqueness in physical property such as Cu atom K-shell ionisation was applied for the enhancement of biological effects in cancer cells.
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PMID:Enhancement of chromosomal aberrations in tumor cells with a non-labeled Cu-PTSM and irradiation with Cu K-shell monochromatic X rays. 1723 44

Osteosarcoma (OSA) is the most common primary bone cancer in children, adolescents and dogs. Current combination surgical and chemotherapeutic treatments have increased survival. However, in recurrent or metastatic disease settings, the prognosis significantly decreases, representing an urgent need for better second-line and novel chemotherapeutics. The current gold standard for combination chemotherapy in OSA often includes a platinum agent, for example, cisplatin or carboplatin. These platinum agents are shuttled within the cell via copper transporters. Recent interest in targeting copper transport has been directed towards antioxidant protein 1 (Atox1) and copper chaperone for superoxide dismutase 1 (CCS), with Atox1 demonstrating the ability to aggregate platinum agents, preventing them from forming DNA adducts. DC_AC50 is a small molecule inhibitor of both Atox1 and CCS. To assess the impact of targeting these pathways on chemotherapy response, two human and two canine OSA cell lines were utilized. After treatment with single agent or combination drugs, cell viability was evaluated and pharmacological synergism calculated using the combination index method. Apoptosis, cell cycle distribution, clonogenic survival and migration were also evaluated. DC_AC50 synergised with carboplatin in combination treatment of human and canine OSA cells to reduce cancer cell viability. DC_AC50-treated cells were significantly less mitotically active, as demonstrated by decreased expression of phospho-histone H3 and cell cycle analysis. DC_AC50 also potentiated carboplatin-induced apoptosis in OSA cells and decreased clonogenic survival. Finally, DC_AC50 reduced the migratory ability of OSA cells. These results justify further investigation into inhibiting intracellular copper chaperones as a means of reducing/preventing acquired chemotherapy resistance.
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PMID:Inhibition of copper chaperones sensitizes human and canine osteosarcoma cells to carboplatin chemotherapy. 3206 Sep 84