Differential sensitivity to platinum-based chemotherapy in primary uterine serous papillary carcinoma cell lines with high vs low HER-2/neu expression in vitro

Sarah N. Cross; Emiliano Cocco; Stefania Bellone; Valsamo K. Anagnostou; Stacey L. Brower; Christine E. Richter; Eric R. Siegel; Peter E. Schwartz; Thomas J. Rutherford; Alessandro D. Santin

doi:10.1016/j.ajog.2010.02.056

Differential sensitivity to platinum-based chemotherapy in primary uterine serous papillary carcinoma cell lines with high vs low HER-2/neu expression in vitro

Sarah N. Cross, Emiliano Cocco, Stefania Bellone, Valsamo K. Anagnostou, Stacey L. Brower, Christine E. Richter, Eric R. Siegel, Peter E. Schwartz, Thomas J. Rutherford, Alessandro D. Santin

Research output: Contribution to journal › Article › peer-review

14 Scopus citations

Abstract

Objective: We sought to identify effective chemotherapy regimens against uterine serous papillary adenocarcinoma (USPC). Study Design: Six USPC, half of which overexpress HER-2/neu at 3+ level, were evaluated for growth rate and in vitro sensitivity to 14 single-agent chemotherapies and 5 combinations by ChemoFx (Precision Therapeutics Inc, Pittsburgh, PA). Results: Cell lines overexpressing HER-2/neu showed higher proliferation when compared to low HER-2/neu-expressing cell lines and a lower half maximum inhibitory concentration (IC₅₀) when exposed to the majority of single-agent chemotherapies. High HER-2/neu expressors were more sensitive to platinum compounds, manifesting a 5.22-fold decrease in carboplatin-IC₅₀ (P = .005) and a 5.37-fold decrease in cisplatin-IC₅₀ (P = .02). When all cell lines were analyzed as a group, chemotherapy agents tested demonstrated lower IC₅₀ when used in combination than as individual agents. Conclusion: USPC overexpressing HER-2/neu display greater in vitro sensitivity to platinum compounds when compared to low HER-2/neu expressors. Higher proliferative capability rather than increased drug resistance may be responsible for the adverse prognosis associated with HER-2/neu overexpression in USPC.

Original language	English (US)
Pages (from-to)	162.e1-162.e8
Journal	American journal of obstetrics and gynecology
Volume	203
Issue number	2
DOIs	https://doi.org/10.1016/j.ajog.2010.02.056
State	Published - 2010
Externally published	Yes

Keywords

HER-2/neu
chemoresistance
chemosensitivity
endometrial neoplasms
uterine serous tumors

ASJC Scopus subject areas

Obstetrics and Gynecology

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10.1016/j.ajog.2010.02.056

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Cross, S. N., Cocco, E., Bellone, S., Anagnostou, V. K., Brower, S. L., Richter, C. E., Siegel, E. R., Schwartz, P. E., Rutherford, T. J., & Santin, A. D. (2010). Differential sensitivity to platinum-based chemotherapy in primary uterine serous papillary carcinoma cell lines with high vs low HER-2/neu expression in vitro. American journal of obstetrics and gynecology, 203(2), 162.e1-162.e8. https://doi.org/10.1016/j.ajog.2010.02.056

Differential sensitivity to platinum-based chemotherapy in primary uterine serous papillary carcinoma cell lines with high vs low HER-2/neu expression in vitro. / Cross, Sarah N.; Cocco, Emiliano; Bellone, Stefania et al.
In: American journal of obstetrics and gynecology, Vol. 203, No. 2, 2010, p. 162.e1-162.e8.

Research output: Contribution to journal › Article › peer-review

Cross, SN, Cocco, E, Bellone, S, Anagnostou, VK, Brower, SL, Richter, CE, Siegel, ER, Schwartz, PE, Rutherford, TJ & Santin, AD 2010, 'Differential sensitivity to platinum-based chemotherapy in primary uterine serous papillary carcinoma cell lines with high vs low HER-2/neu expression in vitro', American journal of obstetrics and gynecology, vol. 203, no. 2, pp. 162.e1-162.e8. https://doi.org/10.1016/j.ajog.2010.02.056

@article{dae31f6842a64131ab569bd7c16dba7f,

title = "Differential sensitivity to platinum-based chemotherapy in primary uterine serous papillary carcinoma cell lines with high vs low HER-2/neu expression in vitro",

abstract = "Objective: We sought to identify effective chemotherapy regimens against uterine serous papillary adenocarcinoma (USPC). Study Design: Six USPC, half of which overexpress HER-2/neu at 3+ level, were evaluated for growth rate and in vitro sensitivity to 14 single-agent chemotherapies and 5 combinations by ChemoFx (Precision Therapeutics Inc, Pittsburgh, PA). Results: Cell lines overexpressing HER-2/neu showed higher proliferation when compared to low HER-2/neu-expressing cell lines and a lower half maximum inhibitory concentration (IC50) when exposed to the majority of single-agent chemotherapies. High HER-2/neu expressors were more sensitive to platinum compounds, manifesting a 5.22-fold decrease in carboplatin-IC50 (P = .005) and a 5.37-fold decrease in cisplatin-IC50 (P = .02). When all cell lines were analyzed as a group, chemotherapy agents tested demonstrated lower IC50 when used in combination than as individual agents. Conclusion: USPC overexpressing HER-2/neu display greater in vitro sensitivity to platinum compounds when compared to low HER-2/neu expressors. Higher proliferative capability rather than increased drug resistance may be responsible for the adverse prognosis associated with HER-2/neu overexpression in USPC.",

keywords = "HER-2/neu, chemoresistance, chemosensitivity, endometrial neoplasms, uterine serous tumors",

author = "Cross, {Sarah N.} and Emiliano Cocco and Stefania Bellone and Anagnostou, {Valsamo K.} and Brower, {Stacey L.} and Richter, {Christine E.} and Siegel, {Eric R.} and Schwartz, {Peter E.} and Rutherford, {Thomas J.} and Santin, {Alessandro D.}",

note = "Funding Information: Supported in part by grants from the Angelo Nocivelli , the Berlucchi , and the Camillo Golgi Foundation , Brescia, Italy; National Institutes of Health (NIH) R01 CA122728-01A2 (Dr Santin); and Grants 501/A3/3 and 0027557 from the Italian Institute of Health (Dr Santin). This investigation was also supported by NIH research Grant no. CA-16359 from the National Cancer Institute . ",

year = "2010",

doi = "10.1016/j.ajog.2010.02.056",

language = "English (US)",

volume = "203",

pages = "162.e1--162.e8",

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T1 - Differential sensitivity to platinum-based chemotherapy in primary uterine serous papillary carcinoma cell lines with high vs low HER-2/neu expression in vitro

AU - Cross, Sarah N.

AU - Cocco, Emiliano

AU - Bellone, Stefania

AU - Anagnostou, Valsamo K.

AU - Brower, Stacey L.

AU - Richter, Christine E.

AU - Siegel, Eric R.

AU - Schwartz, Peter E.

AU - Rutherford, Thomas J.

AU - Santin, Alessandro D.

N1 - Funding Information: Supported in part by grants from the Angelo Nocivelli , the Berlucchi , and the Camillo Golgi Foundation , Brescia, Italy; National Institutes of Health (NIH) R01 CA122728-01A2 (Dr Santin); and Grants 501/A3/3 and 0027557 from the Italian Institute of Health (Dr Santin). This investigation was also supported by NIH research Grant no. CA-16359 from the National Cancer Institute .

PY - 2010

Y1 - 2010

N2 - Objective: We sought to identify effective chemotherapy regimens against uterine serous papillary adenocarcinoma (USPC). Study Design: Six USPC, half of which overexpress HER-2/neu at 3+ level, were evaluated for growth rate and in vitro sensitivity to 14 single-agent chemotherapies and 5 combinations by ChemoFx (Precision Therapeutics Inc, Pittsburgh, PA). Results: Cell lines overexpressing HER-2/neu showed higher proliferation when compared to low HER-2/neu-expressing cell lines and a lower half maximum inhibitory concentration (IC50) when exposed to the majority of single-agent chemotherapies. High HER-2/neu expressors were more sensitive to platinum compounds, manifesting a 5.22-fold decrease in carboplatin-IC50 (P = .005) and a 5.37-fold decrease in cisplatin-IC50 (P = .02). When all cell lines were analyzed as a group, chemotherapy agents tested demonstrated lower IC50 when used in combination than as individual agents. Conclusion: USPC overexpressing HER-2/neu display greater in vitro sensitivity to platinum compounds when compared to low HER-2/neu expressors. Higher proliferative capability rather than increased drug resistance may be responsible for the adverse prognosis associated with HER-2/neu overexpression in USPC.

AB - Objective: We sought to identify effective chemotherapy regimens against uterine serous papillary adenocarcinoma (USPC). Study Design: Six USPC, half of which overexpress HER-2/neu at 3+ level, were evaluated for growth rate and in vitro sensitivity to 14 single-agent chemotherapies and 5 combinations by ChemoFx (Precision Therapeutics Inc, Pittsburgh, PA). Results: Cell lines overexpressing HER-2/neu showed higher proliferation when compared to low HER-2/neu-expressing cell lines and a lower half maximum inhibitory concentration (IC50) when exposed to the majority of single-agent chemotherapies. High HER-2/neu expressors were more sensitive to platinum compounds, manifesting a 5.22-fold decrease in carboplatin-IC50 (P = .005) and a 5.37-fold decrease in cisplatin-IC50 (P = .02). When all cell lines were analyzed as a group, chemotherapy agents tested demonstrated lower IC50 when used in combination than as individual agents. Conclusion: USPC overexpressing HER-2/neu display greater in vitro sensitivity to platinum compounds when compared to low HER-2/neu expressors. Higher proliferative capability rather than increased drug resistance may be responsible for the adverse prognosis associated with HER-2/neu overexpression in USPC.

KW - HER-2/neu

KW - chemoresistance

KW - chemosensitivity

KW - endometrial neoplasms

KW - uterine serous tumors

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DO - 10.1016/j.ajog.2010.02.056

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VL - 203

SP - 162.e1-162.e8

JO - American journal of obstetrics and gynecology

JF - American journal of obstetrics and gynecology

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ER -

Differential sensitivity to platinum-based chemotherapy in primary uterine serous papillary carcinoma cell lines with high vs low HER-2/neu expression in vitro

Abstract

Keywords

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