Expression von Genen mit möglicher prognostischer Bedeutung für das Ansprechen auf Chemotherapie bei Patienten mit Osteosarkom - Gene mit möglicher prognostischer Bedeutung beim Osteosarkom -

Nathrath, Michaela; Kremer, Markus; Letzel, Heinz; Remberger, K.; Höfler, Heinz; Ulle, Tanja

doi:10.1055/s-2002-33189

Cited by 13 publications

(5 citation statements)

References 26 publications

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“…As a structure specific DNA endonuclease, XPF has been reported to bind to double-stranded DNA [20]and further participated in several DNA repair pathways by combining with ERCC1 [21], [22]. As a crucial rate-limiting factor in NER, the low expression of XPF acted as a genetic susceptibility factor in the development of cancers and a prognosis risk factor after chemotherapy in several of cancers, including esophageal cancer [15], [23], [24], [25]. The functional analysis of XPF -673T>C showed that -673T allele had a significantly higher transcriptional activity compared with the -673C allele.…”

Section: Discussionmentioning

confidence: 99%

XPF-673C>T Polymorphism Effect on the Susceptibility to Esophageal Cancer in Chinese Population

et al. 2014

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PurposeXeroderma pigmentsum group F (XPF) plays a pivotal role in DNA nucleotide excision repair and has been linked to the development of various cancers. This study aims to assess the association of XPF genetic variants with the susceptibility to esophageal squamous cell carcinoma (ESCC) in Chinese population.MethodsThis two-stage case-control study was conducted in a total of 1524 patients with ESCC and 1524 controls. Genotype of XPF -673C>T and 11985A>G variants were determined by polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP). Logistic regression analysis was performed to estimate odd ratios (ORs) and 95% confidence intervals (95% CI).ResultsOur case-control study showed that XPF -673TT genotype was associated with a decreased risk of ESCC compared with CC genotype in both case-control sets (Tangshan set: OR = 0.58; 95%CI = 0.34–0.99, P = 0.040; Beijing set: OR = 0.66; 95%CI = 0.46–0.95, P = 0.027). Stratified analyses revealed that a multiplicative interaction between -673C>T variant and age, sex or smoking status was evident (Gene-age: Pinteraction = 0.002; Gene-sex: Pinteraction = 0.002; Gene-smoking: Pinteraction = 0.002). For XPF 11985A>G polymorphism, there was no significant difference of genotype distribution between ESCC cases and controls.ConclusionThese findings indicated that genetic variants in XPF might contribute to the susceptibility to ESCC.

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Section: Discussionmentioning

confidence: 99%

XPF-673C>T Polymorphism Effect on the Susceptibility to Esophageal Cancer in Chinese Population

et al. 2014

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“…Hattinguer et al showed ERCC 1 positivity in 26% of OS patients, which was significantly associated with worse event-free survival and overall survival [141]. Low expression of ERCC4 was correlated with a poor histological response to chemotherapy [142]. Li et al showed that the expression of ERCC4 and ERCC2 in OS cells was greater in patients with high tumor necrosis compared to patients with low tumor necrosis [143].…”

Section: Dna Repair Improvementmentioning

confidence: 99%

Mechanisms of Resistance to Conventional Therapies for Osteosarcoma

Marchandet

Lallier

Charrier

et al. 2021

Cancers

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Osteosarcoma (OS) is the most common primary bone tumor, mainly occurring in children and adolescents. Current standard therapy includes tumor resection associated with multidrug chemotherapy. However, patient survival has not evolved for the past decades. Since the 1970s, the 5-year survival rate is around 75% for patients with localized OS but dramatically drops to 20% for bad responders to chemotherapy or patients with metastases. Resistance is one of the biological processes at the origin of therapeutic failure. Therefore, it is necessary to better understand and decipher molecular mechanisms of resistance to conventional chemotherapy in order to develop new strategies and to adapt treatments for patients, thus improving the survival rate. This review will describe most of the molecular mechanisms involved in OS chemoresistance, such as a decrease in intracellular accumulation of drugs, inactivation of drugs, improved DNA repair, modulations of signaling pathways, resistance linked to autophagy, disruption in genes expression linked to the cell cycle, or even implication of the micro-environment. We will also give an overview of potential therapeutic strategies to circumvent resistance development.

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“…A study has shown a correlation between ERCC4 and the histological response to chemotherapy in OS patients (55). Similarly, the expression of ERCC4 and ERCC2 mRNA in OS cells has been shown to correlate with the chemotherapeutic effect in OS patients (56).…”

Section: Enhanced Dna Repairmentioning

confidence: 99%

Molecular mechanisms of chemoresistance in osteosarcoma (Review)

2014

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Due to the emergence of adjuvant and neoadjuvant chemotherapy, the survival rate has been greatly improved in osteosarcoma (OS) patients with localized disease. However, this survival rate has remained unchanged over the past 30 years, and the long-term survival rate for OS patients with metastatic or recurrent disease remains poor. To a certain extent, the reason behind this may be ascribed to the chemoresistance to anti-OS therapy. Chemoresistance in OS appears to be mediated by numerous mechanisms, which include decreased intracellular drug accumulation, drug inactivation, enhanced DNA repair, perturbations in signal transduction pathways, apoptosis- and autophagy-related chemoresistance, microRNA (miRNA) dysregulation and cancer stem cell (CSC)-mediated drug resistance. In addition, methods employed to circumvent these resistance mechanism have been shown to be effective in the treatment of OS. However, almost all the current studies on the mechanisms of chemoresistance in OS are in their infancy. Further studies are required to focus on the following aspects: i) Improving the delivery of efficacy through novel delivery patterns; ii) improving the understanding of the signal transduction pathways that regulate the proliferation and growth of OS cells; iii) elucidating the signaling pathways of autophagy and its association with apoptosis in OS cells; iv) utilizing high-throughput miRNA expression analysis to identify miRNAs associated with chemoresistance in OS; and v) identifying the role that CSCs play in tumor metastasis and in-depth study of the mechanism of chemoresistance in the CSCs of OS.

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Expression von Genen mit möglicher prognostischer Bedeutung für das Ansprechen auf Chemotherapie bei Patienten mit Osteosarkom - Gene mit möglicher prognostischer Bedeutung beim Osteosarkom -

Abstract: In our retrospective analyses, low expression of ERCC4 was shown to be related to poor response to chemotherapy. The potential value of ERCC4 as response predictor has to be investigated in a prospective study.

Cited by 13 publications

References 26 publications

XPF-673C>T Polymorphism Effect on the Susceptibility to Esophageal Cancer in Chinese Population

XPF-673C>T Polymorphism Effect on the Susceptibility to Esophageal Cancer in Chinese Population

Mechanisms of Resistance to Conventional Therapies for Osteosarcoma

Molecular mechanisms of chemoresistance in osteosarcoma (Review)

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