Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0029463 (osteosarcoma)
 16,637 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Platinum agents cause DNA cross-linking. Nucleotide excision repair genes play a key role in DNA damage repair. This study aims to investigate whether polymorphisms in these genes are associated with tumor response and survival in cisplatin-treated osteosarcoma patients. Eight single nucleotide polymorphisms in ERCC2, XPC, XPA, ERCC1, ERCC4 and ERCC5 genes were analyzed in 91 patients diagnosed with osteosarcoma and treated with cisplatin. A significant association with tumor response, after correction for multiple testing, was found for the Lys751Gln polymorphism in the ERCC2 gene. We found that only 45% of patients with at least one polymorphic G allele responded compared with 80% of patients homozygous for the common T allele (odds ratio=4.9, 95% confidence interval=1.64-14.54, adjusted P-value=0.047). In addition, carrying at least one ERCC2 Lys751GlnG allele was significantly associated with shorter event-free survival (median=184 months, compared with 240 months for TT homozygotes; hazard ratio=5.76, 95% confidence interval=1.30-25.55; P-value=0.021). Although ototoxicity was only recorded in 32 patients, we found weak evidence of an association with the CC genotype of XPC Lys939Gln (P-value= 0.042). This is the first pharmacogenetic study focused on osteosarcoma treatment providing evidence that polymorphic variants in DNA repair genes could be useful predictors of response to cisplatin chemotherapy in osteosarcoma patients.
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PMID:Common variations in ERCC2 are associated with response to cisplatin chemotherapy and clinical outcome in osteosarcoma patients. 1943 73

We investigated the cell-killing efficacy of UV light on cancer cells expressing GFP in the nucleus and RFP in the cytoplasm (dual-color cells). After exposure to various doses of UVA, UVB, or UVC, apoptotic and viable cells were quantitated under fluorescence microscopy using dual-color 143B human osteosarcoma cells, HT-1080 human fibrosarcoma cells, Lewis lung carcinoma (LLC), and XPA-1 human pancreatic cancer cells in vitro. UV-induced cancer cell death was wave-length and dose dependent, as well as cell-line dependent. After UVA exposure, most cells were viable even when the UV dose was increased up to 200 J/m(2). With UVB irradiation, cell death was observed with irradiation at 50 J/m(2). For UVC, as little as 25 J/m(2) UVC irradiation killed approximately 70% of the 143B dual-color cells. This dose of UVB or UVA had almost no effect on the cancer cells. UV-induced cancer cell death varied among the cell lines. Cell death began about 4 h after irradiation and continued until 10 h after irradiation. UVC exposure also suppressed cancer cell growth in nude mice in a model of minimal residual cancer (MRC). No apparent side effects of UVC exposure were observed. This study opens up the possibility of UVC treatment for MRC after surgical resection.
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PMID:UV light killing efficacy of fluorescent protein-expressing cancer cells in vitro and in vivo. 2050 55

The aim of this study was to investigate the role of common polymorphisms in the nucleotide excision repair pathway genes in the tumorigenesis of osteosarcoma and in the response to DNA damaging therapies, such as cisplatin-based neoadjuvant therapy. Excision repair cross-complementing (ERCC) group 2 (XPD; rs13181 and rs1799793), group 5 (XPG; rs17655) and group 1 (XPA; rs3212986 and rs11615) polymorphisms were analyzed in a group of 130 homogenously treated patients with high-grade osteosarcoma, for association with event-free survival (EFS), using the Kaplan-Meier plots and log-rank test. A positive association was observed between both XPD single-nucleotide polymorphisms and an increased EFS (hazards ratio (HR) = 0.34, 95% confidence interval (CI) 0.12-0.98 and HR = 0.19, 95% CI 0.05-0.77, respectively). We had also performed a case-control study for relative risk to develop osteosarcoma. Patients carrying at least one variant allele of XPD rs1799793 had a reduced risk of developing osteosarcoma, compared with wild-type patients (odds ratio = 0.55, 95% CI 0.36-0.84). This study suggests that XPD rs1799793 could be a marker of osteosarcoma associated with features conferring either a better prognosis or a better outcome after platinum therapy, or both.
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PMID:Nucleotide excision repair gene variants and association with survival in osteosarcoma patients treated with neoadjuvant chemotherapy. 2182 87

We analyzed the role of genetic polymorphisms of six important NER pathway genes in response to chemotherapy and clinical outcome of osteosarcoma patients. A prospective study including 172 osteosarcoma patients was conducted between January 2009 and January 2011. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used for ERCC1 rs11615 and rs2298881, ERCC2 rs13181 and rs1799793, ERCC4 rs1800067, ERCC5 rs1047768, XPA 1800975, and XPC rs2228000 and rs2228001 gene polymorphisms. By logistic regression analysis, TT genotype of ERCC1 rs11615 genetic polymorphism was significant correlated with poor response to chemotherapy when compared with wide-type genotype (OR=0.27, 95% CI=0.10-0.71). AC and CC genotype of ERCC1 rs2298881 were significantly associated with poor response to chemotherapy when compared with AA genotype (For AC genotype, OR=0.45, 95% CI=0.21-0.97; for CC genotype, OR=0.19, 95% CI=0.06-0.58). By Cox proportional hazards regression analysis, TT genotype of ERCC1 rs11615 and CC genotype of ERCC1 rs2298881 suffered a 3.16 and 3.57-fold increased hazards of death (For ERCC1 rs11615, HR=3.16, 95% CI=1.19-9.16; for ERCC1 rs2298881, HR=3.57, 95% CI=1.10-11.35). In conclusion, our findings suggest that ERCC1 rs11615 and ERCC1 rs2298881 genetic polymorphisms are significantly associated with poor response to chemotherapy and unfavourable survival of osteosarcoma.
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PMID:Genetic polymorphisms in nucleotide excision repair pathway influences response to chemotherapy and overall survival in osteosarcoma. 2633 55