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106. Myocardial infarction accelerates breast cancer via innate immune reprogramming

Author

Koelwyn, Graeme J., Newman, Alexandra A.C., Afonso, Milessa S., van Solingen, Coen, Corr, Emma M., Brown, Emily J., Albers, Kathleen B., Yamaguchi, Naoko, Narke, Deven, Schlegel, Martin, Sharma, Monika, Shanley, Lianne C., Barrett, Tessa J., Rahman, Karishma, Mezzano, Valeria, Fisher, Edward A., Park, David S., Newman, Jonathan D., Quail, Daniela F., Nelson, Erik R., Caan, Bette J., Jones, Lee W., and Moore, Kathryn J.

Subjects
Heart attack -- Models -- Complications and side effects, Immune response -- Health aspects, Breast cancer -- Models -- Development and progression, Biological sciences, Health
Abstract

Disruption of systemic homeostasis by either chronic or acute stressors, such as obesity.sup.1 or surgery.sup.2, alters cancer pathogenesis. Patients with cancer, particularly those with breast cancer, can be at increased risk of cardiovascular disease due to treatment toxicity and changes in lifestyle behaviors.sup.3-5. While elevated risk and incidence of cardiovascular events in breast cancer is well established, whether such events impact cancer pathogenesis is not known. Here we show that myocardial infarction (MI) accelerates breast cancer outgrowth and cancer-specific mortality in mice and humans. In mouse models of breast cancer, MI epigenetically reprogrammed Ly6C.sup.hi monocytes in the bone marrow reservoir to an immunosuppressive phenotype that was maintained at the transcriptional level in monocytes in both the circulation and tumor. In parallel, MI increased circulating Ly6C.sup.hi monocyte levels and recruitment to tumors and depletion of these cells abrogated MI-induced tumor growth. Furthermore, patients with early-stage breast cancer who experienced cardiovascular events after cancer diagnosis had increased risk of recurrence and cancer-specific death. These preclinical and clinical results demonstrate that MI induces alterations in systemic homeostasis, triggering cross-disease communication that accelerates breast cancer. By reprogramming innate immune cells to an immunosuppressive phenotype, myocardial infarction accelerates breast cancer progression in mice, and the clinical relevance of these findings was demonstrated in individuals with early-stage breast cancer who experienced cardiovascular events after cancer diagnosis., Author(s): Graeme J. Koelwyn [sup.1] , Alexandra A. C. Newman [sup.1] , Milessa S. Afonso [sup.1] , Coen van Solingen [sup.1] , Emma M. Corr [sup.1] , Emily J. Brown [...]

Published
2020
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107. Essays in Development Economics

Author

Park, David Sungho

Subjects
Economics
Abstract

This dissertation contains three essays broadly related to evaluating program effects in developing countries and survey methodology. In Chapter 1, joint work with Naresh Kumar, we evaluate the impact of a multifaceted female empowerment program on reducing intimate partner violence (IPV) in urban Liberia. We ran a randomized controlled trial (RCT) in partnership with the Liberian Red Cross. The program intervention includes intensive psychosocial therapy and vocational skills training throughout a full year. About 12 months after program completion, we find the program significantly reduced the proportion of women who experienced emotional, physical, and sexual IPV by 10-26 percentage points (from control bases of 24-62 percent). While there are multiple pathways through which IPV could be impacted, one channel is that the business training was highly effective: labor supply increased by 37 percent and expenditure by 49 percent. One focus of the program is psychological empowerment, and we find positive but statistically insignificant effects on distress and happiness indices. We also find improvements in social norms around IPV: perceived justifiability of IPV reduced by 0.3 standard deviations.In Chapter 2, joint work with Shilpa Aggarwal, Dahyeon Jeong, Naresh Kumar, Jonathan Robinson and Alan Spearot, we study another important issue in this topic, which is the accurate measurement of IPV. Women may under-report intimate partner violence (IPV) due to several social and psychological factors. We conducted a measurement experiment in rural Liberia and Malawi in which women were asked IPV questions via self-interviewing (SI) or face-to-face interviewing (FTFI). About a third of women incorrectly answered basic screening questions in SI, and SI generates placebo effects on innocuous questions even for those who "pass" screening. Because the probability of responding "yes" to any specific IPV question is less than 50 percent, and that IPV is typically reported as an index (reporting yes to at least one question), such misunderstanding increases IPV reporting. In Malawi, we find that SI increases the reported incidence of any type of IPV by 13 percentage points on a base of 20 percent; in Liberia, we find an insignificant increase of 4 percentage points on a base of 38 percent. Our results suggest SI may spuriously increase reported IPV rates.In Chapter 3, joint work with Shilpa Aggarwal, Dahyeon Jeong, Naresh Kumar, Jonathan Robinson and Alan Spearot, we quantify survey fatigue by randomizing the order of questions in in-person surveys (lasting 2.5 hours on average) fielded in an evaluation of cash transfers in rural Liberia and Malawi. An additional hour of survey time increases the probability that a respondent skips a question by 10-64 percent. Because skips are more common, the total monetary value of aggregated categories such as assets or expenditures declines as the survey goes on, and this effect is sizeable for some categories: for example, an extra hour of survey time lowers food expenditures by 25 percent. Evidence from a similar experiment within high-frequency phone surveys shows that the results are not driven by the respondents deliberately choosing to skip questions in order to hasten the end of the survey, suggesting that cognitive burden is the key driver of survey fatigue.

Published
2022

109. Neuronal cell-based high-throughput screen for enhancers of mitochondrial function reveals luteolin as a modulator of mitochondria-endoplasmic reticulum coupling

Author

Naia, Luana, Pinho, Catarina M., Dentoni, Giacomo, Liu, Jianping, Leal, Nuno Santos, Ferreira, Duarte M. S., Schreiner, Bernadette, Filadi, Riccardo, Fão, Lígia, Connolly, Niamh M. C., Forsell, Pontus, Nordvall, Gunnar, Shimozawa, Makoto, Greotti, Elisa, Basso, Emy, Theurey, Pierre, Gioran, Anna, Joselin, Alvin, Arsenian-Henriksson, Marie, Nilsson, Per, Rego, A. Cristina, Ruas, Jorge L., Park, David, Bano, Daniele, Pizzo, Paola, Prehn, Jochen H. M., and Ankarcrona, Maria

Published
2021
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110. Oral 5-azacytidine and romidepsin exhibit marked activity in patients with PTCL: a multicenter phase 1 study

Author

O'Connor, Owen A., Falchi, Lorenzo, Lue, Jennifer K., Marchi, Enrica, Kinahan, Cristina, Sawas, Ahmed, Deng, Changchun, Montanari, Francesca, Amengual, Jennifer E., Kim, Hye A., Rada, Aishling M., Khan, Karen, Jacob, Alice T., Malanga, Michelle, Francescone, Mark M., Nandakumar, Renu, Soderquist, Craig R., Park, David C., Bhagat, Govind, Cheng, Bin, Risueño, Alberto, Menezes, Daniel, Shustov, Andrei R., Sokol, Lubomir, and Scotto, Luigi

Published
2019
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116. DJ-1 interacts with and regulates paraoxonase-2, an enzyme critical for neuronal survival in response to oxidative stress.

Author

Parsanejad, Mohammad, Bourquard, Noam, Qu, Dianbo, Zhang, Yi, Huang, En, Rousseaux, Maxime WC, Aleyasin, Hossein, Irrcher, Isabella, Callaghan, Steve, Vaillant, Dominique C, Kim, Raymond H, Slack, Ruth S, Mak, Tak W, Reddy, Srinivasa T, Figeys, Daniel, and Park, David S

Subjects
Neurons, Mitochondria, Animals, Humans, Mice, Parkinson Disease, Aryldialkylphosphatase, Intracellular Signaling Peptides and Proteins, Oncogene Proteins, Antioxidants, Apoptosis, Cell Survival, Gene Expression Regulation, Oxidative Stress, HEK293 Cells, Protein Deglycase DJ-1, General Science & Technology
Abstract

Loss-of-function mutations in DJ-1 (PARK7) gene account for about 1% of all familial Parkinson's disease (PD). While its physiological function(s) are not completely clear, DJ-1 protects neurons against oxidative stress in both in vitro and in vivo models of PD. The molecular mechanism(s) through which DJ-1 alleviates oxidative stress-mediated damage remains elusive. In this study, we identified Paraoxonase-2 (PON2) as an interacting target of DJ-1. PON2 activity is elevated in response to oxidative stress and DJ-1 is crucial for this response. Importantly, we showed that PON2 deficiency hypersensitizes neurons to oxidative stress induced by MPP+ (1-methyl-4-phenylpyridinium). Conversely, over-expression of PON2 protects neurons in this death paradigm. Interestingly, PON2 effectively rescues DJ-1 deficiency-mediated hypersensitivity to oxidative stress. Taken together, our data suggest a model by which DJ-1 exerts its antioxidant activities, at least partly through regulation of PON2.

Published
2014

117. The Role of CyberKnife Stereotactic Radiosurgery in Recurrent Cranial Medulloblastomas across Pediatric and Adult Populations †.

Author

Yoo, Kelly H., Marianayagam, Neelan J., Park, David J., Zamarud, Aroosa, Gu, Xuejun, Pollom, Erqi, Soltys, Scott G., Meola, Antonio, and Chang, Steven D.

Subjects
CEREBELLAR tumors, CHILD patients, STEREOTACTIC radiosurgery, TUMORS in children, TREATMENT effectiveness, HEALTH equity, OVERALL survival
Abstract

Background/Objectives: Medulloblastoma is the most common malignant brain tumor in children. In recent decades, the therapeutic landscape has undergone significant changes, with stereotactic radiosurgery (SRS) emerging as a promising treatment for recurrent cases. Our study provides a comprehensive analysis of the long-term efficacy and safety of SRS in recurrent medulloblastomas across both pediatric and adult patients at a single institution. Methods: We retrospectively reviewed the clinical and radiological records of patients who underwent CyberKnife SRS for recurrent cranial medulloblastomas at our institution between 1998 and 2023. Follow-up data were available for 15 medulloblastomas in 10 patients. The cohort comprised eight pediatric patients (ages 3–18) and two adult patients (ages 19–75). The median age at the time of SRS was 13 years, the median tumor volume accounted for 1.9 cc, the median biologically equivalent dose (BED) was 126 Gy, and the single-fraction equivalent dose (SFED) was 18 Gy. The SRS was administered at 75% of the median isodose line. Results: Following a median follow-up of 39 months (range: 6–78), 53.3% of the medulloblastomas progressed, 13.3% regressed, and 33.3% remained stable. The 3-year local tumor control (LTC) rate for all medulloblastomas was 65%, with lower rates observed in the adult cohort (50%) and higher rates in pediatric patients (67%). The 3-year overall survival (OS) rate was 70%, with significantly higher rates in pediatric patients (75%) compared to adult patients (50%). The 3-year progression-free survival (PFS) rate was 58.3%, with higher rates in pediatric patients (60%) compared to adult patients (50%). Two pediatric patients developed radiation-induced edema, while two adult patients experienced radiation necrosis at the latest follow-up, with both adult patients passing away. Conclusions: Our study provides a complex perspective on the efficacy and safety of CyberKnife SRS in treating recurrent cranial medulloblastomas across pediatric and adult populations. The rarity of adverse radiation events (AREs) underscores the safety profile of SRS, reinforcing its role in enhancing treatment outcomes. The intricacies of symptomatic outcomes, intertwined with factors such as age, tumor location, and prior surgeries, emphasize the need for personalized treatment approaches. Our findings underscore the imperative for ongoing research and the development of more refined treatment strategies for recurrent medulloblastomas. Given the observed disparities in treatment outcomes, a more meticulous tailoring of treatment approaches becomes crucial. [ABSTRACT FROM AUTHOR]

Published
2024
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118. P‐13: Excessive Oxygen induced Threshold Voltage Shifts in High Mobility Top‐Gate PrIZO TFTs.

Author

Dong, Yuhua, Ge, Shimin, Cai, Zhihui, Yuan, Dong, Yu, Mingjiue, Pan, Zikang, Li, Shan, Park, David, Xie, Zhongjing, and Xiao, Juncheng

Subjects
THIN film transistors, INDUCTIVE effect, INDIUM oxide, THRESHOLD voltage, ZINC oxide, INDIUM gallium zinc oxide
Abstract

The top gate self‐alignment (TGSA) Praseodymium‐doped indium zinc oxide (PrIZO) thin film transistor (TFT) was fabricated with different process condition in our production line, and high field effect mobility of 40.83 cm2 V‐1 s‐1 was obtained by regulating the GI and ILD parameters. At the same time, the devices show excellent stability with PBTS of 0.52 V and NBTIS of ‐0.9 V, indicating its potential in overcoming the trade‐off between mobility and reliability. [ABSTRACT FROM AUTHOR]

Published
2024
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123. Interaction of interictal epileptiform activity with sleep spindles is associated with cognitive deficits and adverse surgical outcome in pediatric focal epilepsy

Author

Yu, Han, primary, Kim, Woojoong, additional, Park, David K., additional, Phi, Ji Hoon, additional, Lim, Byung Chan, additional, Chae, Jong‐Hee, additional, Kim, Seung‐Ki, additional, Kim, Ki Joong, additional, Provenzano, Frank A., additional, Khodagholy, Dion, additional, and Gelinas, Jennifer N., additional

Published
2023
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126. 666 Safety, efficacy, and biomarker results of SRK-181, a latent TGFβ1 inhibitor, in anti-PD-1 resistant metastatic ccRCC patients

Author

Yap, Timothy, primary, Vaishampayan, Ulka N, additional, Kilari, Deepak, additional, Sweis, Randy, additional, Barve, Minal, additional, Gainor, Justin, additional, Tarhini, Ahmad A, additional, Karim, Raghad, additional, Sher, Amna, additional, Park, David, additional, Babu, Sunil, additional, McKay, Rana, additional, Ju, Yawen, additional, Liu, Lan, additional, Henry, Susan, additional, and Gan, Lu, additional

Published
2023
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130. SAPPHIRE: phase III study of sitravatinib plus nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer

Author

Borghaei, H., primary, de Marinis, F., additional, Dumoulin, D., additional, Reynolds, C., additional, Theelen, W.S.M.E., additional, Percent, I., additional, Gutierrez Calderon, V., additional, Johnson, M.L., additional, Madroszyk-Flandin, A., additional, Garon, E.B., additional, He, K., additional, Planchard, D., additional, Reck, M., additional, Popat, S., additional, Herbst, R.S., additional, Leal, T.A., additional, Shazer, R.L., additional, Yan, X., additional, Harrigan, R., additional, Peters, S., additional, Abdel-Karim, Isam, additional, Abdelsalam, Mahmoud, additional, Addeo, Alfredo, additional, Aguado, Carlos, additional, Alexander, Patrick, additional, Alt, Jürgen, additional, Azzi, Georges, additional, Balaraman, Rama, additional, Biesma, Bonne, additional, Blackhall, Fiona, additional, Bohnet, Sabine, additional, Boleti, Ekaterini, additional, Borghaei, Hossein, additional, Bradbury, Penelope, additional, Brighenti, Matteo, additional, Campbell, Nicholas, additional, Campbell, Toby, additional, Canon, Jean-Luc, additional, Cappuzzo, Federico, additional, Costa, Enric Carcereny, additional, Cavanna, Luigi, additional, Cetnar, Jeremy, additional, Chella, Antonio, additional, Chouaid, Christos, additional, Christoph, Daniel, additional, Castán, Javier Cortés, additional, Dakhil, Shaker, additional, de Castro Carpeño, Francisco Javier, additional, de Marinis, Filippo, additional, Delmonte, Angelo, additional, Demedts, Ingel, additional, Demey, Wim, additional, Dits, Joyce, additional, del Pilar Diz Taín, Maria, additional, Gómez, Manuel Dómine, additional, Dorius, Timothy, additional, Dumoulin, Daphne, additional, Duruisseaux, Michaël, additional, Eaton, Keith, additional, González, Emilio Esteban, additional, Evans, Devon, additional, Faehling, Martin, additional, Farrell, Nicholas, additional, Feinstein, Trevor, additional, Font, Enriqueta Felip, additional, Garcia Campelo, Maria Rosario, additional, Garon, Edward, additional, Garrido López, María Pilar, additional, Germonpré, Paul, additional, Gersten, Todd, additional, Cao, Maria Gonzalez, additional, Gopaluni, Srivalli, additional, Greillier, Laurent, additional, Grossi, Francesco, additional, Guisier, Florian, additional, Gurubhagavatula, Sarada, additional, Calderón, Vanesa Gutiérrez, additional, Hakimian, David, additional, Hall, Richard, additional, Hao, Desirée, additional, Harris, Ronald, additional, Hashemi, Sayed, additional, He, Kai, additional, Hendriks, Lizza, additional, Huang, Chao, additional, Ibrahim, Emad, additional, Jain, Sharad, additional, Johnson, Melissa, additional, Jones, Benjamin, additional, Jones, Monte, additional, Juan Vidal, Óscar José, additional, Juergens, Rosalyn, additional, Kaderbhai, Courèche, additional, Kastelijn, Elisabeth A (Lisanne), additional, Keresztes, Roger, additional, Kio, Ebenezer, additional, Kokowski, Konrad, additional, Konduri, Kartik, additional, Kulkarni, Swati, additional, Kuon, Jonas, additional, Kurkjian, Carla, additional, Labbé, Catherine, additional, Lerner, Rachel, additional, Lim, Farah, additional, Madroszyk-Flandin, Anne, additional, Marathe, Omkar, additional, Martincic, Danko, additional, McClay, Edward, additional, McIntyre, Kristi, additional, Mekhail, Tarek, additional, Misino, Andrea, additional, Molinier, Olivier, additional, Morabito, Alessandro, additional, Morócz, Éva, additional, Müller, Veronika, additional, Nagy, Tünde, additional, Nguyen, Anthony V., additional, Nidhiry, Emmanuel, additional, Okazaki, Ian, additional, Ortega-Granados, Ana Laura, additional, Ostoros, Gyula, additional, Oubre, David, additional, Owen, Scott, additional, Pachipala, Krishna, additional, Park, David, additional, Patel, Pareshkumar, additional, Percent, Ivor, additional, Pérol, Maurice, additional, Peters, Solange, additional, Piet, Berber, additional, Planchard, David, additional, Polychronis, Andreas, additional, Aix, Santiago Ponce, additional, Pons-Tostivint, Elvire, additional, Popat, Sanjaykumar, additional, Pulla, Mariano Provencio, additional, Quantin, Xavier, additional, Quéré, Gilles, additional, Rafique, Noman, additional, Ramaekers, Ryan, additional, Reck, Martin, additional, Reiman, Anthony, additional, Reinmuth, Niels, additional, Reynolds, Craig, additional, Rodríguez-Abreu, Delvys, additional, Romano, Gianpiero, additional, Roque, Tammy, additional, Salzberg, Matthew, additional, Sanborn, Rachel, additional, Sandiego, Sergio, additional, Schaefer, Eric, additional, Schreeder, Marshall, additional, Seetharamu, Nagashree, additional, Seneviratne, Lasika, additional, Shah, Purvi, additional, Shunyakov, Leonid, additional, Slater, Dennis, additional, Parra, Hector Soto, additional, Stigt, Johannes, additional, Stilwill, Joseph, additional, Su, Jingdong, additional, Surmont, Veerle, additional, Swink, Alicia, additional, Szalai, Zsuzsanna, additional, Talbot, Toby, additional, Garcia, Alvaro Taus, additional, Theelen, Willemijn, additional, Thompson, Jonathan, additional, Tiseo, Marcello, additional, Uprety, Dipesh, additional, Uyeki, James, additional, van der Leest, Kornelius Cor, additional, Van Ho, Anthony, additional, van Putten, John, additional, Estévez, Sergio Vázquez, additional, Veatch, Andrea, additional, Vergnenègre, Alain, additional, Ward, Patrick, additional, Weise, Amy, additional, Weiss, Matthias, additional, Whitehurst, Matthew, additional, Zai, Silvia, additional, Zalcman, Gérard, additional, and Zuniga, Richard, additional

Published
2023
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139. Computational Data Sciences and the Regulation of Banking and Financial Services

Author

O’Halloran, Sharyn, Dumas, Marion, Maskey, Sameer, McAllister, Geraldine, Park, David K., Alhajj, Reda, Series editor, Glässer, Uwe, Series editor, Aggarwal, Charu C., Advisory board, Brantingham, Patricia L., Advisory board, Gross, Thilo, Advisory board, Han, Jiawei, Advisory board, Liu, Huan, Advisory board, Manasevich, Raul, Advisory board, Masys, Anthony J., Advisory board, Morselli, Carlo, Advisory board, Wittek, Rafael, Advisory board, Zeng, Daniel, Advisory board, Kaya, Mehmet, editor, Erdoǧan, Özcan, editor, and Rokne, Jon, editor

Published
2017
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140. Randomized phase II study of fulvestrant and erlotinib compared with erlotinib alone in patients with advanced or metastatic non-small cell lung cancer

Author

Garon, Edward B., Siegfried, Jill M., Stabile, Laura P., Young, Patricia A., Marquez-Garban, Diana C., Park, David J., Patel, Ravi, Hu, Eddie H., Sadeghi, Saeed, Parikh, Rupesh J., Reckamp, Karen L., Adams, Brad, Elashoff, Robert M., Elashoff, David, Grogan, Tristan, Wang, He-Jing, Dacic, Sanja, Brennan, Meghan, Valdes, Yacgley, Davenport, Simon, Dubinett, Steven M., Press, Michael F., Slamon, Dennis J., and Pietras, Richard J.

Published
2018
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