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2. AMPK Activation by Metformin Promotes Survival of Dormant ER+ Breast Cancer Cells.

Author

Hampsch, Riley, Wells, Jason, Traphagen, Nicole, McCleery, Charlotte, Fields, Jennifer, Dillon, Lloye, Pooler, Darcy, Lewis, Lionel, Demidenko, Eugene, Huang, Yina, Marotti, Jonathan, Goen, Abigail, Kinlaw, William, Miller, Todd, and Shee, Kevin

Subjects
AMP-Activated Protein Kinases, Animals, Aromatase Inhibitors, Breast Neoplasms, Cell Line, Tumor, Cell Proliferation, Cell Survival, Chemotherapy, Adjuvant, Estrogens, Female, Humans, Metformin, Mice, Neoadjuvant Therapy, Receptors, Estrogen, Signal Transduction, Xenograft Model Antitumor Assays
Abstract

PURPOSE: Despite adjuvant endocrine therapy for patients with estrogen receptor alpha (ER)-positive breast cancer, dormant residual disease can persist for years and eventually cause tumor recurrence. We sought to deduce mechanisms underlying the persistence of dormant cancer cells to identify therapeutic strategies. EXPERIMENTAL DESIGN: Mimicking the aromatase inhibitor-induced depletion of estrogen levels used to treat patients, we developed preclinical models of dormancy in ER+ breast cancer induced by estrogen withdrawal in mice. We analyzed tumor xenografts and cultured cancer cells for molecular and cellular responses to estrogen withdrawal and drug treatments. Publicly available clinical breast tumor gene expression datasets were analyzed for responses to neoadjuvant endocrine therapy. RESULTS: Dormant breast cancer cells exhibited upregulated 5 adenosine monophosphate-activated protein kinase (AMPK) levels and activity, and upregulated fatty acid oxidation. While the antidiabetes AMPK-activating drug metformin slowed the estrogen-driven growth of cells and tumors, metformin promoted the persistence of estrogen-deprived cells and tumors through increased mitochondrial respiration driven by fatty acid oxidation. Pharmacologic or genetic inhibition of AMPK or fatty acid oxidation promoted clearance of dormant residual disease, while dietary fat increased tumor cell survival. CONCLUSIONS: AMPK has context-dependent effects in cancer, cautioning against the widespread use of an AMPK activator across disease settings. The development of therapeutics targeting fat metabolism is warranted in ER+ breast cancer.

Published
2020

3. Laplace’s law of succession estimator and M-statistics.

Author

Demidenko, Eugene

Subjects
*CUMULATIVE distribution function, *INFERENTIAL statistics, *BETA distribution, *STANDARD deviations, *COMMON sense, *CONFIDENCE intervals
Abstract

AbstractThe classic formula for estimating the binomial probability as the proportion of successes contradicts common sense for extreme probabilities when the event never occurs or occurs every time. Laplace’s law of succession estimator, one of the first applications of Bayesian statistics, has been around for over 250 years and resolves the paradoxes, although rarely discussed in modern statistics texts. This work aims to introduce a new theory for exact optimal statistical inference using Laplace’s law of succession estimator as a motivating example. We prove that this estimator may be viewed from a different theoretical perspective as the limit point of the short confidence interval on the double-log scale when the confidence level approaches zero. This motivating example paves the road to the definition of an estimator as the inflection point on the cumulative distribution function as a function of the parameter given the observed statistic. This estimator has the maximum infinitesimal probability of the coverage of the unknown parameter and, therefore, is called the maximum concentration (MC) estimator as a part of a more general M-statistics theory. The new theory is illustrated with exact optimal confidence intervals for the normal standard deviation and the respective MC estimators. [ABSTRACT FROM AUTHOR]

Published
2025
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16. Supplementary Figure S7 from Estrogen Therapy Induces Receptor-Dependent DNA Damage Enhanced by PARP Inhibition in ER+ Breast Cancer

Author

Traphagen, Nicole A., primary, Schwartz, Gary N., primary, Tau, Steven, primary, Roberts, Alyssa M., primary, Jiang, Amanda, primary, Hosford, Sarah R., primary, Marotti, Jonathan D., primary, Goen, Abigail E., primary, Romo, Bianca A., primary, Johnson, Anneka L., primary, Duffy, Emily-Claire K., primary, Demidenko, Eugene, primary, Heverly, Paul, primary, Mosesson, Yaron, primary, Soucy, Shannon M., primary, Kolling, Fred, primary, and Miller, Todd W., primary

Published
2023
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17. Supplementary Table S1 from Estrogen Therapy Induces Receptor-Dependent DNA Damage Enhanced by PARP Inhibition in ER+ Breast Cancer

Author

Traphagen, Nicole A., primary, Schwartz, Gary N., primary, Tau, Steven, primary, Roberts, Alyssa M., primary, Jiang, Amanda, primary, Hosford, Sarah R., primary, Marotti, Jonathan D., primary, Goen, Abigail E., primary, Romo, Bianca A., primary, Johnson, Anneka L., primary, Duffy, Emily-Claire K., primary, Demidenko, Eugene, primary, Heverly, Paul, primary, Mosesson, Yaron, primary, Soucy, Shannon M., primary, Kolling, Fred, primary, and Miller, Todd W., primary

Published
2023
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18. Data from Estrogen Therapy Induces Receptor-Dependent DNA Damage Enhanced by PARP Inhibition in ER+ Breast Cancer

Author

Traphagen, Nicole A., primary, Schwartz, Gary N., primary, Tau, Steven, primary, Roberts, Alyssa M., primary, Jiang, Amanda, primary, Hosford, Sarah R., primary, Marotti, Jonathan D., primary, Goen, Abigail E., primary, Romo, Bianca A., primary, Johnson, Anneka L., primary, Duffy, Emily-Claire K., primary, Demidenko, Eugene, primary, Heverly, Paul, primary, Mosesson, Yaron, primary, Soucy, Shannon M., primary, Kolling, Fred, primary, and Miller, Todd W., primary

Published
2023
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19. Enhancement of Radiation Therapy through Blockade of the Immune Checkpoint, V-domain Ig Suppressor of T Cell Activation (VISTA), in Melanoma and Adenocarcinoma Murine Models

Author

Duval, Kayla E. A., primary, Tavakkoli, Armin D., additional, Kheirollah, Alireza, additional, Soderholm, Haille E., additional, Demidenko, Eugene, additional, Lines, Janet L., additional, Croteau, Walburga, additional, Zhang, Samuel C., additional, Wagner, Robert J., additional, Aulwes, Ethan, additional, Noelle, Randolph J., additional, and Hoopes, P. Jack, additional

Published
2023
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20. Enhancement of Adiation Therapy through Blockade of the Immune Checkpoint VISTA in Melanoma and Adenocarcinoma Murine Models

Author

Duval, Kayla E.A., primary, Tavakkoli, Armin D., additional, Kheirollah, Alireza, additional, Soderholm, Haille E., additional, Demidenko, Eugene, additional, Lines, Janet L., additional, Croteau, Walburga, additional, Wagner, Robert J., additional, Aulwes, Ethan, additional, Noelle, Randolph J., additional, and Hoopes, P. Jack, additional

Published
2023
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21. Supplementary Fig. 1 from Alternating 17β-Estradiol and Aromatase Inhibitor Therapies Is Efficacious in Postmenopausal Women with Advanced Endocrine-Resistant ER+ Breast Cancer

Author

Schwartz, Gary N., primary, Kaufman, Peter A., primary, Giridhar, Karthik V., primary, Marotti, Jonathan D., primary, Chamberlin, Mary D., primary, Arrick, Bradley A., primary, Makari-Judson, Grace, primary, Goetz, Matthew P., primary, Soucy, Shannon M., primary, Kolling, Fred, primary, Demidenko, Eugene, primary, and Miller, Todd W., primary

Published
2023
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22. Supplementary Methods 1 from Alternating 17β-Estradiol and Aromatase Inhibitor Therapies Is Efficacious in Postmenopausal Women with Advanced Endocrine-Resistant ER+ Breast Cancer

Author

Schwartz, Gary N., primary, Kaufman, Peter A., primary, Giridhar, Karthik V., primary, Marotti, Jonathan D., primary, Chamberlin, Mary D., primary, Arrick, Bradley A., primary, Makari-Judson, Grace, primary, Goetz, Matthew P., primary, Soucy, Shannon M., primary, Kolling, Fred, primary, Demidenko, Eugene, primary, and Miller, Todd W., primary

Published
2023
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23. Supplementary Tables 1-8 from Alternating 17β-Estradiol and Aromatase Inhibitor Therapies Is Efficacious in Postmenopausal Women with Advanced Endocrine-Resistant ER+ Breast Cancer

Author

Schwartz, Gary N., primary, Kaufman, Peter A., primary, Giridhar, Karthik V., primary, Marotti, Jonathan D., primary, Chamberlin, Mary D., primary, Arrick, Bradley A., primary, Makari-Judson, Grace, primary, Goetz, Matthew P., primary, Soucy, Shannon M., primary, Kolling, Fred, primary, Demidenko, Eugene, primary, and Miller, Todd W., primary

Published
2023
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24. Data from Alternating 17β-Estradiol and Aromatase Inhibitor Therapies Is Efficacious in Postmenopausal Women with Advanced Endocrine-Resistant ER+ Breast Cancer

Author

Schwartz, Gary N., primary, Kaufman, Peter A., primary, Giridhar, Karthik V., primary, Marotti, Jonathan D., primary, Chamberlin, Mary D., primary, Arrick, Bradley A., primary, Makari-Judson, Grace, primary, Goetz, Matthew P., primary, Soucy, Shannon M., primary, Kolling, Fred, primary, Demidenko, Eugene, primary, and Miller, Todd W., primary

Published
2023
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29. Estrogen Therapy Induces Receptor-Dependent DNA Damage Enhanced by PARP Inhibition in ER+ Breast Cancer

Author

Traphagen, Nicole A., primary, Schwartz, Gary N., additional, Tau, Steven, additional, Roberts, Alyssa M., additional, Jiang, Amanda, additional, Hosford, Sarah R., additional, Marotti, Jonathan D., additional, Goen, Abigail E., additional, Romo, Bianca A., additional, Johnson, Anneka L., additional, Duffy, Emily-Claire K., additional, Demidenko, Eugene, additional, Heverly, Paul, additional, Mosesson, Yaron, additional, Soucy, Shannon M., additional, Kolling, Fred, additional, and Miller, Todd W., additional

Published
2023
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30. Alternating 17beta-estradiol and aromatase inhibitor therapies is efficacious in post-menopausal women with advanced endocrine-resistant ER+ breast cancer

Author

Schwartz, Gary N., primary, Kaufman, Peter A., additional, Giridhar, Karthik V., additional, Marotti, Jonathan D., additional, Chamberlin, Mary D., additional, Arrick, Bradley A., additional, Makari-Judson, Grace, additional, Goetz, Matthew P., additional, Soucy, Shannon M., additional, Kolling, Fred, additional, Demidenko, Eugene, additional, and Miller, Todd W., additional

Published
2023
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34. Enhancing sparse representation of color images by cross channel transformation

Author

Demidenko, Eugene, Rebollo-Neira, Laura, Inacio, Aurelien, Demidenko, Eugene, Rebollo-Neira, Laura, and Inacio, Aurelien

Abstract

Transformations for enhancing sparsity in the approximation of color images by 2D atomic decomposition are discussed. The sparsity is firstly considered with respect to the most significant coefficients in the wavelet decomposition of the color image. The discrete cosine transform is singled out as an effective 3 point transformation for this purpose. The enhanced feature is further exploited by approximating the transformed arrays using an effective greedy strategy with a separable highly redundant dictionary. The relevance of the achieved sparsity is illustrated by a simple encoding procedure. On typical test images the compression at high quality recovery is shown to significantly improve upon JPEG and WebP formats.

Published
2023

35. Supplementary Tables from A Transcriptionally Definable Subgroup of Triple-Negative Breast and Ovarian Cancer Samples Shows Sensitivity to HSP90 Inhibition

Author

Shee, Kevin, primary, Wells, Jason D., primary, Ung, Matthew, primary, Hampsch, Riley A., primary, Traphagen, Nicole A., primary, Yang, Wei, primary, Liu, Stephanie C., primary, Zeldenrust, Megan A., primary, Wang, Liewei, primary, Kalari, Krishna R., primary, Yu, Jia, primary, Boughey, Judy C., primary, Demidenko, Eugene, primary, Kettenbach, Arminja N., primary, Cheng, Chao, primary, Goetz, Matthew P., primary, and Miller, Todd W., primary

Published
2023
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36. Supplementary Data from A Transcriptionally Definable Subgroup of Triple-Negative Breast and Ovarian Cancer Samples Shows Sensitivity to HSP90 Inhibition

Author

Shee, Kevin, primary, Wells, Jason D., primary, Ung, Matthew, primary, Hampsch, Riley A., primary, Traphagen, Nicole A., primary, Yang, Wei, primary, Liu, Stephanie C., primary, Zeldenrust, Megan A., primary, Wang, Liewei, primary, Kalari, Krishna R., primary, Yu, Jia, primary, Boughey, Judy C., primary, Demidenko, Eugene, primary, Kettenbach, Arminja N., primary, Cheng, Chao, primary, Goetz, Matthew P., primary, and Miller, Todd W., primary

Published
2023
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37. Legend for Table S1 from AMPK Activation by Metformin Promotes Survival of Dormant ER+ Breast Cancer Cells

Author

Hampsch, Riley A., primary, Wells, Jason D., primary, Traphagen, Nicole A., primary, McCleery, Charlotte F., primary, Fields, Jennifer L., primary, Shee, Kevin, primary, Dillon, Lloye M., primary, Pooler, Darcy B., primary, Lewis, Lionel D., primary, Demidenko, Eugene, primary, Huang, Yina H., primary, Marotti, Jonathan D., primary, Goen, Abigail E., primary, Kinlaw, William B., primary, and Miller, Todd W., primary

Published
2023
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39. Supplementary Table S1 from AMPK Activation by Metformin Promotes Survival of Dormant ER+ Breast Cancer Cells

Author

Hampsch, Riley A., primary, Wells, Jason D., primary, Traphagen, Nicole A., primary, McCleery, Charlotte F., primary, Fields, Jennifer L., primary, Shee, Kevin, primary, Dillon, Lloye M., primary, Pooler, Darcy B., primary, Lewis, Lionel D., primary, Demidenko, Eugene, primary, Huang, Yina H., primary, Marotti, Jonathan D., primary, Goen, Abigail E., primary, Kinlaw, William B., primary, and Miller, Todd W., primary

Published
2023
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40. Supplementary Figures from AMPK Activation by Metformin Promotes Survival of Dormant ER+ Breast Cancer Cells

Author

Hampsch, Riley A., primary, Wells, Jason D., primary, Traphagen, Nicole A., primary, McCleery, Charlotte F., primary, Fields, Jennifer L., primary, Shee, Kevin, primary, Dillon, Lloye M., primary, Pooler, Darcy B., primary, Lewis, Lionel D., primary, Demidenko, Eugene, primary, Huang, Yina H., primary, Marotti, Jonathan D., primary, Goen, Abigail E., primary, Kinlaw, William B., primary, and Miller, Todd W., primary

Published
2023
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41. Suppl Methods and References from AMPK Activation by Metformin Promotes Survival of Dormant ER+ Breast Cancer Cells

Author

Hampsch, Riley A., primary, Wells, Jason D., primary, Traphagen, Nicole A., primary, McCleery, Charlotte F., primary, Fields, Jennifer L., primary, Shee, Kevin, primary, Dillon, Lloye M., primary, Pooler, Darcy B., primary, Lewis, Lionel D., primary, Demidenko, Eugene, primary, Huang, Yina H., primary, Marotti, Jonathan D., primary, Goen, Abigail E., primary, Kinlaw, William B., primary, and Miller, Todd W., primary

Published
2023
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42. Supplementary data from Strategically Timing Inhibition of Phosphatidylinositol 3-Kinase to Maximize Therapeutic Index in Estrogen Receptor Alpha–Positive, PIK3CA-Mutant Breast Cancer

Author

Yang, Wei, primary, Hosford, Sarah R., primary, Dillon, Lloye M., primary, Shee, Kevin, primary, Liu, Stephanie C., primary, Bean, Jennifer R., primary, Salphati, Laurent, primary, Pang, Jodie, primary, Zhang, Xiaolin, primary, Nannini, Michelle A., primary, Demidenko, Eugene, primary, Bates, Darcy, primary, Lewis, Lionel D., primary, Marotti, Jonathan D., primary, Eastman, Alan R., primary, and Miller, Todd W., primary

Published
2023
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43. Supplementary Figure 1 from Blockade of the Ubiquitin Protease UBP43 Destabilizes Transcription Factor PML/RARα and Inhibits the Growth of Acute Promyelocytic Leukemia

Author

Guo, Yongli, primary, Dolinko, Andrey V., primary, Chinyengetere, Fadzai, primary, Stanton, Bruce, primary, Bomberger, Jennifer M., primary, Demidenko, Eugene, primary, Zhou, Da-Cheng, primary, Gallagher, Robert, primary, Ma, Tian, primary, Galimberti, Fabrizio, primary, Liu, Xi, primary, Sekula, David, primary, Freemantle, Sarah, primary, and Dmitrovsky, Ethan, primary

Published
2023
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44. Data from Blockade of the Ubiquitin Protease UBP43 Destabilizes Transcription Factor PML/RARα and Inhibits the Growth of Acute Promyelocytic Leukemia

Author

Guo, Yongli, primary, Dolinko, Andrey V., primary, Chinyengetere, Fadzai, primary, Stanton, Bruce, primary, Bomberger, Jennifer M., primary, Demidenko, Eugene, primary, Zhou, Da-Cheng, primary, Gallagher, Robert, primary, Ma, Tian, primary, Galimberti, Fabrizio, primary, Liu, Xi, primary, Sekula, David, primary, Freemantle, Sarah, primary, and Dmitrovsky, Ethan, primary

Published
2023
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45. Estrogen therapy induces receptor-dependent DNA damage enhanced by PARP inhibition in ER+ breast cancer

Author

Traphagen, Nicole A, primary, Schwartz, Gary N., additional, Tau, Steven, additional, Jiang, Amanda, additional, Hosford, Sarah R., additional, Goen, Abigail E., additional, Roberts, Alyssa M., additional, Romo, Bianca A., additional, Johnson, Anneka L., additional, Duffy, Emily-Claire K., additional, Demidenko, Eugene, additional, Heverly, Paul, additional, Mosesson, Yaron, additional, Soucy, Shannon M., additional, Kolling, Fred, additional, and Miller, Todd W., additional

Published
2023
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48. Kolmogorov-Smirnov Test for Image Comparison

Author

Demidenko, Eugene, Kanade, Takeo, editor, Kittler, Josef, editor, Kleinberg, Jon M., editor, Mattern, Friedemann, editor, Mitchell, John C., editor, Nierstrasz, Oscar, editor, Pandu Rangan, C., editor, Steffen, Bernhard, editor, Sudan, Madhu, editor, Terzopoulos, Demetri, editor, Tygar, Dough, editor, Vardi, Moshe Y., editor, Weikum, Gerhard, editor, Laganá, Antonio, editor, Gavrilova, Marina L., editor, Kumar, Vipin, editor, Mun, Youngsong, editor, Tan, C. J. Kenneth, editor, and Gervasi, Osvaldo, editor

Published
2004
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