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103 results on '"Schreiber, Anna"'

11. Ausblick

Author

Claus, Mareen, primary, Dahlmüller, Till, additional, Manzel, Melissa, additional, Prieß, Vera, additional, Schreiber, Anna, additional, and Theuerkauf, Erik, additional

Published
2023
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17. First-in-Human Dose-Escalation Study of the Novel Oral Depsipeptide Class I-Targeting HDAC Inhibitor Bocodepsin (OKI-179) in Patients with Advanced Solid Tumors

Author

Schreiber, Anna R., primary, Kagihara, Jodi A., additional, Corr, Bradley R., additional, Davis, S. Lindsey, additional, Lieu, Christopher, additional, Kim, Sunnie S., additional, Jimeno, Antonio, additional, Camidge, D. Ross, additional, Williams, Jud, additional, Heim, Amy M., additional, Martin, Anne, additional, DeMattei, John A., additional, Holay, Nisha, additional, Triplett, Todd A., additional, Eckhardt, S. Gail, additional, Litwiler, Kevin, additional, Winkler, James, additional, Piscopio, Anthony D., additional, and Diamond, Jennifer R., additional

Published
2023
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20. First-in-Human Dose-Escalation Study of the Novel Oral Depsipeptide Class I-Targeting HDAC Inhibitor Bocodepsin (OKI-179) in Patients with Advanced Solid Tumors.

Author

Schreiber, Anna R., Kagihara, Jodi A., Corr, Bradley R., Davis, S. Lindsey, Lieu, Christopher, Kim, Sunnie S., Jimeno, Antonio, Camidge, D. Ross, Williams, Jud, Heim, Amy M., Martin, Anne, DeMattei, John A., Holay, Nisha, Triplett, Todd A., Eckhardt, S. Gail, Litwiler, Kevin, Winkler, James, Piscopio, Anthony D., and Diamond, Jennifer R.

Subjects
*THERAPEUTIC use of antineoplastic agents, *DRUG dosage, *DRUG tolerance, *CLINICAL trials, *NAUSEA, *TIME, *PROTEIN kinase inhibitors, *TREATMENT duration, *CANCER patients, *DESCRIPTIVE statistics, *RESEARCH funding, *TUMORS, *HISTONE deacetylase, *FATIGUE (Physiology), *THROMBOCYTOPENIA, *DRUG toxicity, *PATIENT safety, *CHEMICAL inhibitors
Abstract

Simple Summary: Histone deacetylase (HDAC) inhibitors are anti-cancer agents that have demonstrated efficacy in hematologic malignancies; however, the utility of available agents is limited, owing to narrow therapeutic indices and suboptimal isoform selectivity. Bocodepsin (OKI-179) is a novel, orally bioavailable, Class I-targeting depsipeptide HDAC inhibitor with promising anti-cancer activity in preclinical solid tumor models. In this first-in-human phase I clinical study, we report the safety and tolerability of OKI-179 administered orally daily with intermittent and continuous dosing schedules. OKI-179 was well tolerated with low rates of high-grade adverse events, supporting the potential for the successful combination of OKI-179 with other targeted anti-cancer agents. OKI-179 is currently being investigated in combination with the MEK inhibitor binimetinib in patients with NRAS-mutated melanoma. (1) Background: Histone deacetylases (HDACs) play a critical role in epigenetic signaling in cancer; however, available HDAC inhibitors have limited therapeutic windows and suboptimal pharmacokinetics (PK). This first-in-human phase I dose escalation study evaluated the safety, PK, pharmacodynamics (PDx), and efficacy of the oral Class I-targeting HDAC inhibitor bocodepsin (OKI-179). (2) Patients and Methods: Patients (n = 34) with advanced solid tumors were treated with OKI-179 orally once daily in three schedules: 4 days on 3 days off (4:3), 5 days on 2 days off (5:2), or continuous in 21-day cycles until disease progression or unacceptable toxicity. Single-patient escalation cohorts followed a standard 3 + 3 design. (3) Results: The mean duration of treatment was 81.2 (range 11–447) days. The most frequent adverse events in all patients were nausea (70.6%), fatigue (47.1%), and thrombocytopenia (41.2%). The maximum tolerated dose (MTD) of OKI-179 was 450 mg with 4:3 and 200 mg with continuous dosing. Dose-limiting toxicities included decreased platelet count and nausea. Prolonged disease control was observed, including two patients with platinum-resistant ovarian cancer. Systemic exposure to the active metabolite exceeded the preclinical efficacy threshold at doses lower than the MTD and was temporally associated with increased histone acetylation in circulating T cells. (4) Conclusions: OKI-179 has a manageable safety profile at the recommended phase 2 dose (RP2D) of 300 mg daily on a 4:3 schedule with prophylactic oral antiemetics. OKI-179 is currently being investigated with the MEK inhibitor binimetinib in patients with NRAS-mutated melanoma in the phase 2 Nautilus trial. [ABSTRACT FROM AUTHOR]

Published
2024
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21. Elucidating the direct effects of the novel HDAC inhibitor bocodepsin (OKI-179) on T cells to rationally design regimens for combining with immunotherapy

Author

Holay, Nisha, primary, Somma, Alexander, additional, Duchow, Mark, additional, Soleimani, Milad, additional, Capasso, Anna, additional, Kottapalli, Srividya, additional, Rios, Joshua, additional, Giri, Uma, additional, Diamond, Jennifer, additional, Schreiber, Anna, additional, Piscopio, Anthony D., additional, Van Den Berg, Carla, additional, Eckhardt, S. Gail, additional, and Triplett, Todd A., additional

Published
2023
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22. A Case of Fetal-Induced Graft-versus-Host Disease

Author

Schreiber, Anna R., primary, Santos, Jennifer, additional, McMahon, Brandon, additional, Buckner, Tyler W., additional, Olson, Courtney, additional, Alberti, Michael O., additional, Guimarães-Young, Amy, additional, Knoeckel, Christopher, additional, Broussard, Lindsey, additional, Aubrey, Michael, additional, Palmer, Brent E., additional, Weiss, Emma, additional, Connors, Geoffrey R., additional, Brunner, Selene, additional, Wisell, Joshua A., additional, Pacheco, Theresa, additional, Aisner, Dara L., additional, and Gutman, Jonathan A., additional

Published
2023
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24. Supplementary Tables and Figures from Cabozantinib Exhibits Potent Antitumor Activity in Colorectal Cancer Patient-Derived Tumor Xenograft Models via Autophagy and Signaling Mechanisms

Author

Scott, Aaron J., primary, Arcaroli, John J., primary, Bagby, Stacey M., primary, Yahn, Rachel, primary, Huber, Kendra M., primary, Serkova, Natalie J., primary, Nguyen, Anna, primary, Kim, Jihye, primary, Thorburn, Andrew, primary, Vogel, Jon, primary, Quackenbush, Kevin S., primary, Capasso, Anna, primary, Schreiber, Anna, primary, Blatchford, Patrick, primary, Klauck, Peter J., primary, Pitts, Todd M., primary, Eckhardt, S. Gail, primary, and Messersmith, Wells A., primary

Published
2023
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25. The emergence of targeted therapy for HER2-low triple-negative breast cancer: a review of fam-trastuzumab deruxtecan.

Author

Schreiber, Anna R., O'Bryant, Cindy L., Kabos, Peter, and Diamond, Jennifer R.

Subjects
TRIPLE-negative breast cancer, EPIDERMAL growth factor receptors, HORMONE receptor positive breast cancer, CLINICAL trials, INTERSTITIAL lung diseases, DNA topoisomerase I, ANTIBODY-drug conjugates
Abstract

Metastatic triple-negative breast cancer (TNBC) is an aggressive sub-type of breast cancer. Despite recent advances, metastatic TNBC remains difficult to treat with limited targeted treatment options. Fam-trastuzumab deruxtecan (T-DXd), is a novel antibody-drug conjugate (ADC) targeting human epidermal growth factor receptor 2 (HER2) and is composed of a unique linker bound to the topoisomerase I inhibitor DXd. T-DXd has significant anti-tumor activity in patients with HER2-low TNBC. This review reports on the mechanism, pre-clinical/clinical studies, efficacy, and tolerability of T-DXd. A literature search was conducted via PubMed using keywords such as 'fam-trastuzumab deruxtecan,' 'Enhertu,' and 'HER2-low cancers.' The Phase III Destiny-Breast04 Trial showed benefit in progression-free and overall survival in patients with HER2-low metastatic breast cancers treated with T-DXd compared to treatment of physician's choice chemotherapy. T-DXd is the first pharmaceutical to effectively target a HER2-low population with clinically meaningful efficacy in patients with HER2-low TNBC. Compared to chemotherapy, T-DXd has a similar safety profile, with the additional need for close monitoring for interstitial lung disease. Given the clinical activity of T-DXd in TNBC, it is likely there will be continued efforts to refine HER2-low diagnostics and to develop additional ADCs with other protein targets. [ABSTRACT FROM AUTHOR]

Published
2023
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26. The lncRNANeat1is associated with astrocyte reactivity and memory deficits in a mouse model of Alzheimer’s disease

Author

Irwin, Ashleigh B, Martina, Verdion, Sint Jago, Silvienne C, Bahabry, Rudhab, Schreiber, Anna Maria, and Lubin, Farah D.

Subjects
Article
Abstract

Dysregulation of long non-coding RNAs (lncRNAs) have been associated with Alzheimer’s disease (AD). However, the functional role of lncRNAs in AD remains unclear. Here, we report a crucial role for the lncRNANeat1in astrocyte dysfunction and memory deficits associated with AD. Transcriptomics analysis show abnormally high expression levels ofNEAT1in the brains of AD patients relative to aged-matched healthy controls, with the most significantly elevated levels in glial cells. In a human transgenic APP-J20 (J20) mouse model of AD, RNA-fluorescentin situhybridization characterization ofNeat1expression in hippocampal astrocyte versus non-astrocyte cell populations revealed a significant increase inNeat1expression in astrocytes of male, but not female, mice. This corresponded with increased seizure susceptibility in J20 male mice. Interestingly,Neat1deficiency in the dCA1 in J20 male mice did not alter seizure threshold. Mechanistically,Neat1deficiency in the dorsal area CA1 of the hippocampus (dCA1) J20 male mice significantly improved hippocampus-dependent memory.Neat1deficiency also remarkably reduced astrocyte reactivity markers suggesting thatNeat1overexpression is associated with astrocyte dysfunction induced by hAPP/Aβ in the J20 mice. Together, these findings indicate that abnormalNeat1overexpression may contribute to memory deficits in the J20 AD model not through altered neuronal activity, but through astrocyte dysfunction.

Published
2023

28. Abstract CT120: Phase II study of radiotherapy in combination with chemotherapy and immunotherapy in patients with PD-L1-positive metastatic triple-negative breast cancer

Author

Schreiber, Anna R., primary, Kagihara, Jodi, additional, Nicklawsky, Andrew, additional, Gao, Dexiang, additional, Afghahi, Anosheh, additional, Elias, Anthony, additional, Kabos, Peter, additional, Shagisultanova, Elena, additional, Pitts, Todd, additional, Lang, Julie, additional, Karam, Sana, additional, Borges, Virginia, additional, Fisher, Christine, additional, and Diamond, Jennifer R., additional

Published
2022
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30. Abstract 3509: Immune modulation in immune co-cultures of pancreatic ductal adenocarcinoma by small molecule CLK/WNT pathway inhibitor SM04690

Author

Dominguez, Adrian TA, primary, Real, Adreanna G., additional, Levandowski, Cecilia B., additional, Lewis, Matthew S., additional, Hartman, Sarah, additional, Yacob, Betelehem, additional, Smoots, Stephen, additional, Schreiber, Anna, additional, Lanis, Jordi, additional, Nepal, Pragya, additional, Diamond, Jennifer, additional, Lieu, Chris, additional, Messersmith, Wells, additional, Lang, Julie, additional, and Pitts, Todd, additional

Published
2022
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31. Selected Histone Deacetylase Inhibitors Reverse the Frataxin Transcriptional Defect in a Novel Friedreich’s Ataxia Induced Pluripotent Stem Cell-Derived Neuronal Reporter System

Author

Schreiber, Anna M., Li, Yanjie, Chen, Yi-Hsien, Napierala, Jill S., and Napierala, Marek

Subjects
General Neuroscience
Abstract

Friedreich’s ataxia (FRDA) is a neurodegenerative disorder caused by the expansion of guanine–adenine–adenine repeats within the first intron of the frataxin (FXN) gene. The location and nature of the expansion have been proven to contribute to transcriptional repression of FXN by decreasing the rate of polymerase II (RNA polymerase II) progression and increasing the presence of histone modifications associated with a heterochromatin-like state. Targeting impaired FXN transcription appears as a feasible option for therapeutic intervention, while no cure currently exists. We created a novel reporter cell line containing an FXN-Nanoluciferase (FXN-NLuc) fusion in induced pluripotent stem cells (iPSCs) reprogrammed from the fibroblasts of patients with FRDA, thus allowing quantification of endogenous FXN expression. The use of iPSCs provides the opportunity to differentiate these cells into disease-relevant neural progenitor cells (NPCs). NPCs derived from the FXN-NLuc line responded to treatments with a known FXN inducer, RG109. Results were validated by quantitative PCR and Western blot in multiple FRDA NPC lines. We then screened a commercially available library of compounds consisting of molecules targeting various enzymes and pathways critical for silencing or activation of gene expression. Only selected histone deacetylase inhibitors were capable of partial reactivation of FXN expression. This endogenous, FRDA iPSC-derived reporter can be utilized for high-throughput campaigns performed in cells most relevant to disease pathology in search of FXN transcription activators.

Published
2022

32. The importance of early ADHD diagnosis for young adults' wellbeing and future employment

Author

Holm, Jens and Schreiber, Anna

Subjects
Psykologi, välbefinnande, adhd, Psychology, diagnos
Abstract

Adhd är idag vanligt förekommande och flera studier bekräftar att andelen individer som får diagnosen adhd ökar. I genomsnitt är det 6-9 % av alla barn över hela världen som idag får diagnosen adhd. En tidig diagnos anses vara avgörande för att möjliggöra lämpliga insatser och behandling. Avsaknad av forskning om huruvida en tidig diagnos som barn har betydelse för individens välbefinnande senare i livet är dock stor. Syftet med denna studie har varit att undersöka om där finns ett samband mellan en tidig diagnos och ett ökat välbefinnandet i vuxen ålder samt om det ökar möjligheten attetablera sig på arbetsmarknaden. Studien genomfördes med kvantitativ ansats och riktade sig till unga vuxna i ålder 20 till 26 år med en adhd-diagnos. Totalt ingick 35 deltagare i studien. Pearsons korrelationskoefficient beräknades för att identifiera samband mellan ålder vid diagnos och välbefinnande i ung vuxen ålder. Resultatet visade på en signifikant negativ korrelation mellan de två variablerna, r(31) = -0.602 , p< .001, vilket ger ett visst stöd för hypotesen att en tidig diagnos har en positiv inverkanpå välbefinnandet som ung vuxen. Several studies confirm that the proportion of individuals diagnosed with ADHD in the world is increasing. As many as 6-9% of all children worldwide are diagnosed with ADHD. An early diagnosis is considered as crucial to enable appropriate interventions and treatment. However, there is a lack of research on whether an early diagnosis as a child has a positive impact on the individual's well-being later in life. The purpose of this study has been to investigate whether there is a relationship between an early diagnosis and an increased well-being in adulthood and whether it also increases the possibility of establishing oneself in the labor market. The study was conducted with a quantitative approach and was aimed at young adults aged 20 to 26 years who have an ADHD diagnosis. The study included 35 participants. Pearson's correlation coefficient was calculated to identify the relationship between age at diagnosis and well-being in young adulthood. The results showed a significant negative correlation between the two variables, r (31) = -0.602, p

Published
2022

34. Evaluating anthracycline + taxane versus taxane-based chemotherapy in older women with node-negative triple-negative breast cancer: a SEER-Medicare study

Author

Schreiber, Anna R., primary, Kagihara, Jodi, additional, Eguchi, Megan, additional, Kabos, Peter, additional, Fisher, Christine M., additional, Meyer, Elisabeth, additional, Molina, Elizabeth, additional, Kondapalli, Lavanya, additional, Bradley, Cathy J., additional, and Diamond, Jennifer R., additional

Published
2021
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47. Evaluation of TAK-264, an Antibody-Drug Conjugate in Pancreatic Cancer Cell Lines and Patient-Derived Xenograft Models

Author

Schreiber, Anna R., primary, Nguyen, Anna, additional, Bagby, Stacey M., additional, Arcaroli, John J., additional, Yacob, Betelehem W., additional, Quackenbush, Kevin, additional, Guy, Joe L., additional, Crowell, Thomas, additional, Stringer, Bradley, additional, Danaee, Hadi, additional, Kalebic, Thea, additional, Messersmith, Wells A., additional, and Pitts, Todd M., additional

Published
2018
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48. Cabozantinib Exhibits Potent Antitumor Activity in Colorectal Cancer Patient-Derived Tumor Xenograft Models via Autophagy and Signaling Mechanisms

Author

Scott, Aaron J., primary, Arcaroli, John J., additional, Bagby, Stacey M., additional, Yahn, Rachel, additional, Huber, Kendra M., additional, Serkova, Natalie J., additional, Nguyen, Anna, additional, Kim, Jihye, additional, Thorburn, Andrew, additional, Vogel, Jon, additional, Quackenbush, Kevin S., additional, Capasso, Anna, additional, Schreiber, Anna, additional, Blatchford, Patrick, additional, Klauck, Peter J., additional, Pitts, Todd M., additional, Eckhardt, S. Gail, additional, and Messersmith, Wells A., additional

Published
2018
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50. Abstract B050: Evaluation of TAK-264, a novel antibody-drug conjugate in pancreatic cancer cell lines and patient-derived xenograft models

Author

Schreiber, Anna R., primary, Nguyen, Anna, additional, Bagby, Stacey M., additional, Yacob, Betelehem, additional, Quackenbush, Kevin, additional, Guy, Joe L., additional, Crowell, Thomas, additional, Stringer, Bradley, additional, Danaee, Hadi, additional, Kalebic, Thea, additional, Messersmith, Wells A., additional, Arcaroli, John J., additional, and Pitts, Todd M., additional

Published
2018
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