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T-DM1, a novel antibody-drug conjugate, is highly effective against primary HER2 overexpressing uterine serous carcinoma in vitro and in vivo.

English DP, Bellone S, Schwab CL, Bortolomai I, Bonazzoli E, Cocco E, Buza N, Hui P, Lopez S, Ratner E, Silasi DA, Azodi M, Schwartz PE, Rutherford TJ, Santin AD - Cancer Med (2014)

Bottom Line: T-DM1 was considerably more effective than trastuzumab in inhibiting cell proliferation and in causing apoptosis (P = 0.004) of USC showing HER2 overexpression.T-DM1 shows promising antitumor effect in HER2-positive USC cell lines and USC xenografts and its activity is significantly higher when compared to T.T-DM1 may represent a novel treatment option for HER2-positive USC patients with disease refractory to trastuzumab and traditional chemotherapy.

View Article: PubMed Central - PubMed

Affiliation: Division of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, Connecticut, 06520.

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Cell cycle figure showing the absence of G2/M phase arrest in epidermal growth factor receptor-2 (HER2) nonoverexpressing cell line after treatment with T-DM1. The majority of the cells are in the S phase as shown in figure with the minority of the cells in the G2/M phase.
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fig05: Cell cycle figure showing the absence of G2/M phase arrest in epidermal growth factor receptor-2 (HER2) nonoverexpressing cell line after treatment with T-DM1. The majority of the cells are in the S phase as shown in figure with the minority of the cells in the G2/M phase.

Mentions: Next, we evaluated by cell cycle analysis whether T-DM1 may induce G2/M phase arrest and apoptosis in high HER2-expressing cells. In multiple experiments, we found the percentage of cells in G2/M phase to shift from a mean of 21.85 ± 1.89% in the pretreatment HER2 high expressor cell lines to a mean of 51 ± 8.9% (P = 0.01) after 48–72 h of exposure to 2 μg/mL of T-DM1. T-DM1 showed activity (i.e., induction of G2/M phase arrest and apoptosis) against all USC cell lines tested including cell lines endowed with primary resistance to the cytostatic effects of T. In contrast, no significant G2/M phase arrest was noted in low expressor HER2 cell lines after exposure to T-DM1 (Fig.5).


T-DM1, a novel antibody-drug conjugate, is highly effective against primary HER2 overexpressing uterine serous carcinoma in vitro and in vivo.

English DP, Bellone S, Schwab CL, Bortolomai I, Bonazzoli E, Cocco E, Buza N, Hui P, Lopez S, Ratner E, Silasi DA, Azodi M, Schwartz PE, Rutherford TJ, Santin AD - Cancer Med (2014)

Cell cycle figure showing the absence of G2/M phase arrest in epidermal growth factor receptor-2 (HER2) nonoverexpressing cell line after treatment with T-DM1. The majority of the cells are in the S phase as shown in figure with the minority of the cells in the G2/M phase.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4302675&req=5

fig05: Cell cycle figure showing the absence of G2/M phase arrest in epidermal growth factor receptor-2 (HER2) nonoverexpressing cell line after treatment with T-DM1. The majority of the cells are in the S phase as shown in figure with the minority of the cells in the G2/M phase.
Mentions: Next, we evaluated by cell cycle analysis whether T-DM1 may induce G2/M phase arrest and apoptosis in high HER2-expressing cells. In multiple experiments, we found the percentage of cells in G2/M phase to shift from a mean of 21.85 ± 1.89% in the pretreatment HER2 high expressor cell lines to a mean of 51 ± 8.9% (P = 0.01) after 48–72 h of exposure to 2 μg/mL of T-DM1. T-DM1 showed activity (i.e., induction of G2/M phase arrest and apoptosis) against all USC cell lines tested including cell lines endowed with primary resistance to the cytostatic effects of T. In contrast, no significant G2/M phase arrest was noted in low expressor HER2 cell lines after exposure to T-DM1 (Fig.5).

Bottom Line: T-DM1 was considerably more effective than trastuzumab in inhibiting cell proliferation and in causing apoptosis (P = 0.004) of USC showing HER2 overexpression.T-DM1 shows promising antitumor effect in HER2-positive USC cell lines and USC xenografts and its activity is significantly higher when compared to T.T-DM1 may represent a novel treatment option for HER2-positive USC patients with disease refractory to trastuzumab and traditional chemotherapy.

View Article: PubMed Central - PubMed

Affiliation: Division of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, Connecticut, 06520.

Show MeSH
Related in: MedlinePlus