Chemotherapy resistance and oncogene expression in non–small cell lung cancer

d’Amato, Thomas A.; Landreneau, Rodney J.; Ricketts, William; Huang, Weidong; Parker, Ricardo J.; Mechetner, Eugene; Yu, Ing-Ru; Luketich, James D.

doi:10.1016/j.jtcvs.2006.10.019

Cited by 43 publications

(33 citation statements)

References 29 publications

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“…The results of biomarker testing by immunohistochemistry and flow cytometry on the primary ovarian tumor were abstracted from the database [19]. These biomarker evaluations for immunohistochemistry and flow cytometry were performed by Oncotech Inc. as part of routine clinical testing by using the fresh tumor samples obtained by pathologist at the time of primary cytoreductive surgery as described previously [20][21][22]; tumor tissues were also processed for formalin fixation for H&E staining. The H&E slides from the primary ovarian tumor specimens and metastatic sites were used for evaluation of tumoral LVSI.…”

Section: Discussionmentioning

confidence: 99%

Estrogen receptor expression and increased risk of lymphovascular space invasion in high-grade serous ovarian carcinoma

Matsuo

Todd

Yoshino

et al. 2013

Gynecologic Oncology

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Objective-Recent studies have demonstrated that lymphovascular space invasion (LVSI) is associated with increased risk of hematogenous and lymphatic metastasis and poor clinical outcome of women with epithelial ovarian cancer. Given the suspected role of estrogen in promoting ovarian cancer metastasis, we examined potential links between estrogen receptor and LVSI in high-grade serous ovarian carcinoma.Methods-Tumoral expression of ER, PR, p53, MDR1, EGFR, HER2, DNA ploidy, and S-phase fraction was examined for 121 cases of stage I-IV high-grade serous ovarian carcinoma samples obtained at primary cytoreductive surgery. Biomarker expression was correlated to LVSI and survival outcomes.Results-LVSI was observed in 101 (83.5%) of all cases. Immunohistochemistry of tested biomarkers showed ER (86.7%) to be the most commonly expressed followed by p53 (71.4%), Conclusion-Our data demonstrated that estrogen receptor was positively correlated with LVSI that was an independent prognostic indicator of poor survival outcomes of high-grade serous ovarian carcinoma. This study emphasizes the importance of estrogen pathway in promoting lymphatic or vascular spread of high-grade serous ovarian carcinoma.

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Section: Discussionmentioning

confidence: 99%

Estrogen receptor expression and increased risk of lymphovascular space invasion in high-grade serous ovarian carcinoma

Matsuo

Todd

Yoshino

et al. 2013

Gynecologic Oncology

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“…Results of phase II clinical trials of picoplatin have shown survival benefit in ovarian, NSCLC, and SCLC patients (20). The chemotherapeutic treatment of NSCLC by platinum agents has been hampered by rapid development of resistance (21). Consideration of picoplatin as a potential treatment for NSCLC led us to determine the role of OCT-mediated uptake in its lung cancer efficacy.…”

Section: Discussionmentioning

confidence: 99%

Organic Cation Transporters Modulate the Uptake and Cytotoxicity of Picoplatin, a Third-Generation Platinum Analogue

Yee

et al. 2010

Molecular Cancer Therapeutics

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Picoplatin, a third-generation platinum agent, is efficacious against lung cancers that are otherwise resistant or become refractory during platinum treatment. This effort was aimed at the determination of the influence of organic cation transporters 1, 2, and 3 (OCT1, OCT2, and OCT3) and their genetic variants on cellular uptake of picoplatin and on the individual components of the ensuing cytotoxicity such as DNA adduct formation. The effect of OCT1 on picoplatin pharmacokinetics and antitumor efficacy was determined using OCT knockout mice and HEK293 xenografts stably expressing OCT1. The uptake and DNA adduct formation of picoplatin were found to be significantly enhanced by the expression of the OCTs. Expression of OCT1 and OCT2, but not OCT3, significantly enhanced picoplatin cytotoxicity, which was reduced in the presence of an OCT inhibitor. Common reduced functional variants of OCT1 and OCT2 led to reduction in uptake and DNA adduct formation of picoplatin in comparison with the reference OCT1 and OCT2. Pharmacokinetic parameters of picoplatin in Oct1−/− and Oct1+/+ mice were not significantly different, suggesting that the transporters do not influence the disposition of the drug. In contrast, the volume of OCT1-expressing xenografts in mice was significantly reduced by picoplatin treatment, suggesting that OCT1 may enhance the antitumor efficacy of picoplatin. These studies provide a basis for follow-up clinical studies that would seek to examine the relationship between the anticancer efficacy of picoplatin and expression levels of OCTs and their genetic variants in tumors.

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“…The results of biomarker testing by immunohistochemistry and flow cytometry on the primary ovarian tumor were abstracted from the database [19]. These biomarker evaluations for immunohistochemistry and flow cytometry were performed by Oncotech Inc. as part of routine clinical testing by using the fresh tumor samples obtained by pathologist at the time of primary cytoreductive surgery as described previously [20-22]; tumor tissues were also processed for formalin fixation for H&E staining. The H&E slides from the primary ovarian tumor specimens and metastatic sites were used for evaluation of tumoral LVSI.…”

Section: Methodsmentioning

confidence: 99%

Estrogen receptor expression and increased risk of lymphovascular space invasion in high-grade serous ovarian carcinoma

Matsuo

Sheridan

Mabuchi

et al. 2014

Gynecologic Oncology

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Objective Recent studies have demonstrated that lymphovascular space invasion (LVSI) is associated with increased risk of hematogenous and lymphatic metastasis and poor clinical outcome of women with epithelial ovarian cancer. Given the suspected role of estrogen in promoting ovarian cancer metastasis, we examined potential links between estrogen receptor and LVSI in high-grade serous ovarian carcinoma. Methods Tumoral expression of ER, PR, p53, MDR1, EGFR, HER2, DNA ploidy, and S-phase fraction was examined for 121 cases of stage I-IV high-grade serous ovarian carcinoma samples obtained at primary cytoreductive surgery. Biomarker expression was correlated to LVSI and survival outcomes. Results LVSI was observed in 101 (83.5%) of all cases. Immunohistochemistry of tested biomarkers showed ER (86.7%) to be the most commonly expressed followed by p53 (71.4%), HER2 (68.3%), EGFR (52.1%), MDR-1 (14.3%), and PR (8.9%). ER expression was positively correlated to PR expression (r=0.31, p=0.001). LVSI was only correlated with ER (odds ratio 6.27, 95%CI 1.93-20.4, p=0.002) but not with other biomarkers. In multivariate analysis, ER remained significantly associated with LVSI (p=0.039). LVSI remained a significant prognostic factor for decreased progression-free survival (HR 3.01, 95%CI 1.54-5.88, p=0.001) and overall survival (HR 2.69, 95%CI 1.18-6.23, p=0.021) while ER-expression did not remain as a significant variable in multivariate analysis. Conclusion Our data demonstrated that estrogen receptor was positively correlated with LVSI that was an independent prognostic indicator of poor survival outcomes of high-grade serous ovarian carcinoma. This study emphasizes the importance of estrogen pathway in promoting lymphatic or vascular spread of high-grade serous ovarian carcinoma.

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Chemotherapy resistance and oncogene expression in non–small cell lung cancer

Abstract: Multi-drug chemotherapy resistance in non-small cell lung cancer tumor cultures is common, and associations between molecular markers and in vitro chemotherapy resistance are noted. Clinical validation through integration of such testing into clinical trials seems warranted.

Cited by 43 publications

References 29 publications

Estrogen receptor expression and increased risk of lymphovascular space invasion in high-grade serous ovarian carcinoma

Estrogen receptor expression and increased risk of lymphovascular space invasion in high-grade serous ovarian carcinoma

Organic Cation Transporters Modulate the Uptake and Cytotoxicity of Picoplatin, a Third-Generation Platinum Analogue

Estrogen receptor expression and increased risk of lymphovascular space invasion in high-grade serous ovarian carcinoma

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