Interrelationships between Cellular Nucleotide Excision Repair, Cisplatin Cytotoxicity, HER‐2/<i>neu</i> Gene Expression, and Epidermal Growth Factor Receptor Level in Non‐small Cell Lung Cancer Cells

Tsai, Chun‐Ming; Chang, Kuo-Ting; Lan, Li; Perng, Reury-Perng; Yang, Liying

doi:10.1111/j.1349-7006.2000.tb00934.x

Cited by 25 publications

(15 citation statements)

References 45 publications

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“…One possible mechanism of cisplatin resistance is through alterations in cellular proteins involved in DNA-damage repair and in growth and apoptosis signaling (22)(23)(24)(25)(26)(27). Preliminary observations showed microsatellite instability and inactivating homozygous deletions of the 3 ¶ coding region of NPRL2 in various human primary tumors and suggested that NPRL2 may be a novel 3p mismatch repair gene (4,6).…”

Section: Discussionmentioning

confidence: 99%

The 3p21.3 Tumor Suppressor NPRL2 Plays an Important Role in Cisplatin-Induced Resistance in Human Non–Small-Cell Lung Cancer Cells

et al. 2006

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NPRL2 is one of the novel candidate tumor suppressor genes identified in the human chromosome 3p21.3 region. The NPRL2 has shown potent tumor suppression activity in vitro and in vivo and has been suggested to be involved in DNA mismatch repair, cell cycle checkpoint signaling, and regulation of the apoptotic pathway. In this study, we analyzed the endogenous expression of the NPRL2 protein and the cellular response to cisplatin in 40 non-small-cell lung cancer cell lines and found that expression of NPRL2 was significantly and reciprocally correlated to cisplatin sensitivity, with a Spearman correlation coefficient of À0.677 (P < 0.00001). Exogenously introduced expression of NPRL2 by N-[1-(2,3-dioleoyloxyl)propyl]-NNN-trimethylammoniummethyl sulfate: cholesterol nanoparticle-mediated gene transfer significantly resensitized the response to cisplatin, yielding a 40% greater inhibition of tumor cell viability and resulting in a 2-to 3-fold increase in induction of apoptosis by activation of multiple caspases in NPRL2-transfected cells compared with untransfected cells at an equal dose of cisplatin. Furthermore, a systemic treatment with a combination of NPRL2 nanoparticles and cisplatin in a human H322 lung cancer orthotopic mouse model significantly enhanced the therapeutic efficacy of cisplatin and overcame cisplatin-induced resistance (P < 0.005). These findings implicate the potential of NPRL2 as a biomarker for predicting cisplatin response in lung cancer patients and as a molecular therapeutic agent for enhancing response and resensitizing nonresponders to cisplatin treatment.

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Section: Discussionmentioning

confidence: 99%

The 3p21.3 Tumor Suppressor NPRL2 Plays an Important Role in Cisplatin-Induced Resistance in Human Non–Small-Cell Lung Cancer Cells

et al. 2006

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“…In vitro and in vivo studies have demonstrated how the individual overexpression of EGFR and c-erbB-2 is associated with greater resistance to radiotherapy [17,31,32,33,34] and a lower sensitivity to cisplatin [35, 36] in several tumor types.…”

Section: Discussionmentioning

confidence: 99%

Negative Prognostic Impact of the Coexpression of Epidermal Growth Factor Receptor and c-erbB-2 in Locally Advanced Cervical Cancer

et al. 2009

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Objective: The objective was to determine the impact of the coexpression of epidermal growth factor receptor (EGFR) and tumor marker c-erbB-2 on disease-free survival (DFS) and pelvic relapse-free survival (PRFS) in patients with locally advanced cervical cancer (LACC) receiving concurrent chemoradiotherapy. Methods: The expression of EGFR and c-erbB-2 was assessed by immunohistochemistry, which was centralized and blinded to outcome. Univariate and multivariate analyses were used to evaluate the impact of EGFR and c-erbB-2 on DFS and PRFS. Results: 170 patients with LACC were included and received concurrent chemoradiotherapy. 25 (15%) biopsies were considered EGFR and c-erbB-2 positive; 100 (59%) were either EGFR or c-erbB-2 positive, and 45 (26%) were EGFR and c-erbB-2 negative. The 3- and 5-year DFS was 39% each for EGFR- and c-erbB-2-positive patients, 54 and 49%, respectively, for EGFR- or c-erbB-2-positive patients, and 76 and 72%, respectively, for EGFR- and c-erbB-2-negative patients (p = 0.006). EGFR- and c-erbB-2-positive tumors were significantly associated with a decrease in PRFS (hazard ratio, HR, 3.99; 95% confidence interval, CI, 1.44–11.05, p = 0.007), and DFS (HR 2.9; 95% CI, 1.26–6.66, p = 0.01). Conclusion: Patients with LACC coexpressing EGFR and c-erbB-2, and treated with concurrent chemoradiotherapy, had a worse clinical prognosis with shorter DFS and PRFS.

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“…198 Interestingly, experimental but also clinical evidence have linked expression levels of ERCC1, a component of the NER pathway, to lack of sensitivity to platinum compounds in different malignant conditions, including cancers of the ovary, 199 stomach, 200 endometrium 201 and lung, as well as head and neck cancer-derived cell lines. 202,203 The fact that ERCC1 expression levels correlated to poor survival in lung cancer patients treated with platinum-based chemotherapy 204 indicates an association between ERCC1 expression levels and chemosensitivity, although a prognostic effect not related to therapy may not be excluded. variant associated with lower enzyme activity of the xeroderma pigmentosum group D gene has been linked to higher response rate to combined treatment with 5-fluorouracil and oxaliplatin in colorectal cancer.…”

Section: Nucleotide Excision Repairmentioning

confidence: 99%

Mapping genetic alterations causing chemoresistance in cancer: identifying the roads by tracking the drivers

Lønning

Knappskog

2013

Oncogene

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Although new agents are implemented to cancer therapy, we lack fundamental understandings of the mechanisms of chemoresistance, the main obstacle to cure in cancer. Here we review clinical evidence linking molecular defects to drug resistance across different tumour forms and discuss contemporary experimental evidence exploring these mechanisms. Although evidence, in general, is sparse and fragmentary, merging knowledge links drug resistance, and also sensitivity, to defects in functional pathways having a key role in cell growth arrest or death and DNA repair. As these pathways may act in concert, there is a need to explore multiple mechanisms in parallel. Taking advantage of massive parallel sequencing and other novel high-throughput technologies and base research on biological hypotheses, we now have the possibility to characterize functional defects related to these key pathways and to design a new generation of studies identifying the mechanisms controlling resistance to different treatment regimens in different tumour forms.

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Interrelationships between Cellular Nucleotide Excision Repair, Cisplatin Cytotoxicity, HER‐2/neu Gene Expression, and Epidermal Growth Factor Receptor Level in Non‐small Cell Lung Cancer Cells

Cited by 25 publications

References 45 publications

The 3p21.3 Tumor Suppressor NPRL2 Plays an Important Role in Cisplatin-Induced Resistance in Human Non–Small-Cell Lung Cancer Cells

The 3p21.3 Tumor Suppressor NPRL2 Plays an Important Role in Cisplatin-Induced Resistance in Human Non–Small-Cell Lung Cancer Cells

Negative Prognostic Impact of the Coexpression of Epidermal Growth Factor Receptor and c-erbB-2 in Locally Advanced Cervical Cancer

Mapping genetic alterations causing chemoresistance in cancer: identifying the roads by tracking the drivers

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