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1. Exploiting metabolic vulnerabilities after anti-VEGF antibody therapy in ovarian cancer

Author

Glassman, Deanna, Kim, Mark S., Spradlin, Meredith, Badal, Sunil, Taki, Mana, Bhattacharya, Pratip, Dutta, Prasanta, Kingsley, Charles V., Foster, Katherine I., Animasahun, Olamide, Jeon, Jin Heon, Achreja, Abhinav, Jayaraman, Anusha, Kumar, Praveen, Nenwani, Minal, Wuchu, Fulei, Bayraktar, Emine, Wu, Yutuan, Stur, Elaine, Mangala, Lingegowda, Lee, Sanghoon, Yap, Timothy A., Westin, Shannon N., Eberlin, Livia S., Nagrath, Deepak, and Sood, Anil K.

Published
2023
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2. Serial cytoreductive surgery and survival outcomes in recurrent adult-type ovarian granulosa cell tumors

Author

How, Jeffrey A., primary, Legarreta, Alejandra Flores, additional, Handley, Katelyn F., additional, Fellman, Bryan, additional, Foster, Katherine I., additional, Glassman, Deanna, additional, Vuttaradhi, Veena K., additional, Brodsky, Allison L., additional, Lawson, Barrett, additional, Frumovitz, Michael, additional, Westin, Shannon N., additional, Ramondetta, Lois M., additional, Gershenson, David M., additional, Sood, Anil K., additional, and Hillman, R. Tyler, additional

Published
2024
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4. Mechanism and rational combinations with GP‐2250, a novel oxathiazine derivative, in ovarian cancer.

Author

Kim, Mark S., Glassman, Deanna, Handley, Katelyn F., Lankenau Ahumada, Adrian, Jennings, Nicholas B., Bayraktar, Emine, Foster, Katherine, Joseph, Robiya, Lee, Sanghoon, Coleman, Robert L., and Sood, Anil K.

Subjects
*PROTEIN microarrays, *POLY(ADP-ribose) polymerase, *ANNEXINS, *PROTEIN expression, *LABORATORY mice, *OVARIAN cancer
Abstract

Background: GP‐2250, a novel analog of taurultam (TRLT), has emerged as a potent anti‐neoplastic drug; however, the mechanisms underlying its effects are not well understood. Here, we investigated the mechanism of action and the biological effects of GP‐2250 using in vitro and in vivo models. Methods: We carried out a series of in vitro (MTT assay, Annexin V/PI assay, colony formation assay, reverse‐phase protein array [RPPA], and HRLC/IC analysis) to determine the biological activity of GP‐2250 and investigate the mechanism of action. In vivo experiments were carried out to determine the therapeutic efficacy of GP‐2250 alone and in combination with standard‐of‐care drugs (e.g., paclitaxel, cisplatin, topotecan, and poly ADP‐ribose polymerase [PARP] inhibitors). Results: We investigated the cytotoxic effect of GP‐2250 in 10 ovarian cancer cell lines and found GP‐2250 combined with a PARP inhibitor had the greatest synergy. RPPA revealed that GP‐2250 inhibited hypoxia‐inducible factor‐1α, AKT, and mammalian target of rapamycin (mTOR) activation and expression. High‐resolution mass spectrometry revealed that hexokinase2 activity and protein expression were significantly reduced by GP‐2250 exposure. Furthermore, GP‐2250 reduced glycolysis and ATP synthesis in cancer cells. An in vivo pharmacodynamic experiment using the OVCAR8 mouse model demonstrated that 500 mg/kg GP‐2250 was effective in downregulating AKT and mTOR activation and expression. In the in vivo therapy experiment using an orthotopic mouse model, a combination of GP‐2250 with either PARP inhibitors or bevacizumab showed a significant reduction of tumor weights and nodules compared to those treated with a vehicle, control IgG groups, or monotherapy groups. Conclusions: Taken together, our data indicate that GP‐2250 exerts profound effects on tumor metabolism and, in combination with PARP inhibitors or bevacizumab, showed promising anti‐tumor efficacy. These findings could have implications for the clinical development of GP‐2250. [ABSTRACT FROM AUTHOR]

Published
2024
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7. Supplementary Data from Rational Combination of CRM1 Inhibitor Selinexor and Olaparib Shows Synergy in Ovarian Cancer Cell Lines and Mouse Models

Author

Handley, Katelyn F., primary, Rodriguez-Aguayo, Cristian, primary, Ma, Shaolin, primary, Stur, Elaine, primary, Joseph, Robiya, primary, Bayraktar, Emine, primary, Dasari, Santosh K., primary, Nguyen, Nghi, primary, Powell, Reid T., primary, Sobieski, Mary, primary, Ivan, Cristina, primary, Kim, Mark, primary, Umamaheswaran, Sujanitha, primary, Glassman, Deanna, primary, Wen, Yunfei, primary, Amero, Paola, primary, Stephan, Clifford, primary, Coleman, Robert L., primary, Landesman, Yosef, primary, Westin, Shannon N., primary, Ram, Prahlad T., primary, and Sood, Anil K., primary

Published
2023
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9. Clinical implications of tumor‐based next‐generation sequencing in high‐grade epithelial ovarian cancer

Author

Foster, Katherine I., primary, Shaw, Kenna R. M., additional, Jin, Jeff, additional, Westin, Shannon N., additional, Yap, Timothy A., additional, Glassman, Deanna M., additional, Jazaeri, Amir A., additional, Rauh‐Hain, Jose A., additional, Lee, Sanghoon, additional, Fellman, Bryan M., additional, Ju, Zhenlin, additional, Liu, Yuexin, additional, Fleming, Nicole D., additional, and Sood, Anil K., additional

Published
2023
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10. Endothelial p130cas confers resistance to anti-angiogenesis therapy

Author

Wen, Yunfei, primary, Chelariu-Raicu, Anca, additional, Umamaheswaran, Sujanitha, additional, Nick, Alpa M., additional, Stur, Elaine, additional, Hanjra, Pahul, additional, Jiang, Dahai, additional, Jennings, Nicholas B., additional, Chen, Xiuhui, additional, Corvigno, Sara, additional, Glassman, Deanna, additional, Lopez-Berestein, Gabriel, additional, Liu, Jinsong, additional, Hung, Mien-Chie, additional, and Sood, Anil K., additional

Published
2023
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13. Classification of High-Grade Serous Ovarian Cancer Using Tumor Morphologic Characteristics

Author

Handley, Katelyn F., primary, Sims, Travis T., additional, Bateman, Nicholas W., additional, Glassman, Deanna, additional, Foster, Katherine I., additional, Lee, Sanghoon, additional, Yao, Jun, additional, Yao, Hui, additional, Fellman, Bryan M., additional, Liu, Jinsong, additional, Lu, Zhen, additional, Conrads, Kelly A., additional, Hood, Brian L., additional, Barakat, Waleed, additional, Zhao, Li, additional, Zhang, Jianhua, additional, Westin, Shannon N., additional, Celestino, Joseph, additional, Rangel, Kelly M., additional, Badal, Sunil, additional, Pereira, Igor, additional, Ram, Prahlad T., additional, Maxwell, George L., additional, Eberlin, Livia S., additional, Futreal, P. Andrew, additional, Bast, Robert C., additional, Fleming, Nicole D., additional, Conrads, Thomas P., additional, and Sood, Anil K., additional

Published
2022
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14. What’s next after bevaciumab resistance? Targeting metabolic vulnerabilities in ovarian cancer (022)

Author

Glassman, Deanna, primary, Kim, Mark, additional, Badal, Sunil, additional, Spradlin, Meredith, additional, Animasahun, Olamide, additional, Jeon, Jin Heon, additional, Achreja, Abhinav, additional, Jayaraman, Anusha, additional, Kumar, Praveen, additional, Nenwani, Minal, additional, Wuchu, Fulei, additional, Bayraktar, Emine, additional, Wu, Yutuan, additional, Stur, Elaine, additional, Mangala, Lingegowda, additional, Lee, Sanghoon, additional, Yap, Timothy, additional, Westin, Shannon, additional, Eberlin, Livia Schiavinato, additional, Nagrath, Deepak, additional, and Sood, Anil, additional

Published
2022
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18. Why are thromboembolic events so common in ovarian cancer? An investigation of tumor-mediated molecular markers (236)

Author

Glassman, Deanna, primary, Bateman, Nicholas, additional, Conrads, Thomas, additional, Lee, Sanghoon, additional, Zhao, Li, additional, Ivan, Cristina, additional, Rangel, Kelly, additional, Zhang, Jianhua, additional, Futreal, P. Andrew, additional, Afshar-Kharghan, Vahid, additional, Maxwell, George, additional, Yao, Jun, additional, Tan, Yukun, additional, Chen, Ken, additional, and Sood, Anil, additional

Published
2022
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20. Abstract 2484: Hyperpolarized magnetic resonance spectroscopy assessment of the metabolic effects of glutaminase inhibitor therapy in an ovarian cancer model

Author

Glassman, Deanna, primary, Kim, Mark S., additional, Dutta, Prasanta, additional, Kingsley, Charles V., additional, Bayraktar, Emine, additional, Wu, Yutuan, additional, Stur, Elaine, additional, Mangala, Lingegowda S., additional, Foster, Katherine, additional, Lee, Sanghoon, additional, Yap, Timothy A., additional, Westin, Shannon N., additional, Bhattacharya, Pratip, additional, and Sood, Anil K., additional

Published
2022
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21. Endothelial p130cas confers resistance to anti-angiogenesis therapy

Author

Wen, Yunfei, primary, Chelariu-Raicu, Anca, additional, Umamaheswaran, Sujanitha, additional, Nick, Alpa M., additional, Stur, Elaine, additional, Hanjra, Pahul, additional, Jiang, Dahai, additional, Jennings, Nicholas B., additional, Chen, Xiuhui, additional, Corvigno, Sara, additional, Glassman, Deanna, additional, Lopez-Berestein, Gabriel, additional, Liu, Jinsong, additional, Hung, Mien-Chie, additional, and Sood, Anil K., additional

Published
2022
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22. Molecular Correlates of Venous Thromboembolism (VTE) in Ovarian Cancer

Author

Glassman, Deanna, primary, Bateman, Nicholas W., additional, Lee, Sanghoon, additional, Zhao, Li, additional, Yao, Jun, additional, Tan, Yukun, additional, Ivan, Cristina, additional, Rangel, Kelly M., additional, Zhang, Jianhua, additional, Conrads, Kelly A., additional, Hood, Brian L., additional, Abulez, Tamara, additional, Futreal, P. Andrew, additional, Fleming, Nicole D., additional, Afshar-Kharghan, Vahid, additional, Maxwell, George L., additional, Conrads, Thomas P., additional, Chen, Ken, additional, and Sood, Anil K., additional

Published
2022
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23. Rational Combination of CRM1 Inhibitor Selinexor and Olaparib Shows Synergy in Ovarian Cancer Cell Lines and Mouse Models

Author

Handley, Katelyn F., primary, Rodriguez-Aguayo, Cristian, additional, Ma, Shaolin, additional, Stur, Elaine, additional, Joseph, Robiya, additional, Bayraktar, Emine, additional, Dasari, Santosh K., additional, Nguyen, Nghi, additional, Powell, Reid T., additional, Sobieski, Mary, additional, Ivan, Cristina, additional, Kim, Mark, additional, Umamaheswaran, Sujanitha, additional, Glassman, Deanna, additional, Wen, Yunfei, additional, Amero, Paola, additional, Stephan, Clifford, additional, Coleman, Robert L., additional, Landesman, Yosef, additional, Westin, Shannon N., additional, Ram, Prahlad T., additional, and Sood, Anil K., additional

Published
2021
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25. If looks could kill: morphologic subtypes of high-grade serous ovarian cancer

Author

Handley, Katelyn, primary, Sims, Travis, additional, Glassman, Deanna, additional, Fleming, Nicole, additional, Lee, Sanghoon, additional, Fellman, Bryan, additional, Yao, Hui, additional, Yao, Jun, additional, Liu, Jinsong, additional, Bast, Robert, additional, Lu, Zhen, additional, Westin, Shannon, additional, Rangel, Kelly, additional, Celestino, Joseph, additional, Bateman, Nicholas, additional, Conrads, Thomas, additional, Maxwell, George, additional, Ram, Prahlad, additional, and Sood, Anil, additional

Published
2021
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30. Targeting CCR2+ macrophages with BET inhibitor overcomes adaptive resistance to anti-VEGF therapy in ovarian cancer.

Author

Wu, Yutuan, Jennings, Nicholas B., Sun, Yunjie, Dasari, Santosh K., Bayraktar, Emine, Corvigno, Sara, Stur, Elaine, Glassman, Deanna, Mangala, Lingegowda S., Lankenau Ahumada, Adrian, Westin, Shannon N., Sood, Anil K., and Hu, Wei

Subjects
OVARIAN cancer, MACROPHAGES, ENDOTHELIAL growth factors, CANCER treatment, CANCER cells, VASCULAR endothelial growth factor antagonists, RANIBIZUMAB
Abstract

Purpose: Tumor-associated macrophages (TAMs) are known to contribute to adaptive resistance to anti-vascular endothelial growth factor (VEGF) antibody (AVA) therapy in ovarian cancer. BET (bromodomain and extra-terminal domain) inhibitors (BETi) may have unique roles in targeting TAMs. Our objective was to examine the effects of BETi on TAMs, especially in the context of enhancing the efficacy of AVA therapy. Methods: We conducted a series of in vitro (MTT assay, apoptosis, flow cytometry, and RNA sequencing) and in vivo (xenograft ovarian cancer model) experiments to determine the biological effects of BETi combined with AVA in ovarian cancer. For statistical analysis, a two-tailed Student's t test (equal variance) or ANOVA was used for multiple groups' comparison, and p < 0.05 was considered significant. Results: BETi resulted in a dose-dependent decrease in cell viability and induced apoptosis (p < 0.01) in ovarian cancer cells (SKOV3ip1, OVCAR5, and OVCAR8). Treatment with BETi significantly increased apoptosis in THP-1 monocytes and macrophages (PMA-differentiated THP-1; p < 0.01). Furthermore, BETi selectively induced greater apoptosis in M2-like macrophages (PMA and IL-4, IL-13-differentiated THP-1) (31.3%-36.1%) than in M1-like macrophages (PMA and LPS-differentiated THP-1) (12.4%-18.5%) (p < 0.01). Flow cytometry revealed that the percentage of M1-like macrophages (CD68+/CD80+) was significantly increased after treatment with low-dose BETi (ABBV-075 0.1 µM; p < 0.05), whereas the percentage of CD68+/CCR2+ macrophages was significantly decreased (p < 0.001); these findings suggest that BETi may selectively inhibit the survival of CCR2+ macrophages and re-polarize the macrophages into an M1-like phenotype. RNA-seq analysis revealed that BETi selectively targeted macrophage infiltration-related cytokines/chemokines in ovarian cancer (adjusted p < 0.05 and Log2 fold change ≥ 1.5). Finally, using in vivo ovarian cancer models, compared with control or monotherapy, the combination of BETi (ABBV-075) and bevacizumab resulted in greater inhibition of tumor growth and macrophage infiltration (p < 0.05) and longer survival of tumor-bearing mice (p < 0.001). Conclusions: Our findings indicate a previously unrecognized role for BETi in selectively targeting CCR2+ TAMs and enhancing the efficacy of AVA therapy in ovarian cancer. [ABSTRACT FROM AUTHOR]

Published
2022
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34. Raven Surgical Robot Training in Preparation for da Vinci® Use: A Randomized Prospective Trial.

Author

GLASSMAN, Deanna, WHITE, Lee, LEWIS, Andrew, KING, Hawkeye, CLARKE, Alicia, GLASSMAN, Thomas, COMSTOCK, Bryan, HANNAFORD, Blake, and LENDVAY, Thomas S.

Abstract

The rapid adoption of robotic assisted surgery challenges the pace at which adequate robotic training can occur due to access limitations to the da Vinci robot. Thirty medical students completed a randomized controlled trial evaluating whether the Raven robot could be used as an alternative training tool for the Fundamentals of Laparoscopic Surgery (FLS) block transfer task on the da Vinci robot. Two groups, one trained on the da Vinci and one trained on the Raven, were tested on a criterion FLS block transfer task on the da Vinci. After robotic FLS block transfer proficiency training there was no statistically significant difference between path length (p=0.39) and economy of motion scores (p=0.06) between the two groups, but those trained on the da Vinci did have faster task times (p=0.01). These results provide evidence for the value of using the Raven robot for training prior to using the da Vinci surgical system for similar tasks. [ABSTRACT FROM AUTHOR]

Published
2014
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