A5011913247- RNA modifications and cancer
- Cancer-related molecular mechanisms research
- HER2/EGFR in Cancer Research
- Monoclonal and Polyclonal Antibodies Research
- Cancer therapeutics and mechanisms
- Ferroptosis and cancer prognosis
- Epigenetics and DNA Methylation
- Mitochondrial Function and Pathology
- Cancer, Lipids, and Metabolism
- Cancer, Hypoxia, and Metabolism
- Radiomics and Machine Learning in Medical Imaging
- Receptor Mechanisms and Signaling
- Estrogen and related hormone effects
- Iron Metabolism and Disorders
- Cancer-related gene regulation
- Brain Metastases and Treatment
- Metalloenzymes and iron-sulfur proteins
- HVDC Systems and Fault Protection
Hospital for Sick Children
2022-2024
University of Toronto
2022-2024
Zymeworks (Canada)
2024
Lundbeck (United States)
2024
Abstract In recent years, the field of antibody drug conjugates (ADC) has seen a resurgence, largely driven by clinical benefit observed in patients treated with ADCs incorporating camptothecin-based topoisomerase I inhibitor payloads. Herein, we present development novel camptothecin ZD06519 (FD1), which been specifically designed for its application as an ADC payload. A panel analogs different substituents at C-7 and C-10 positions core was prepared tested vitro. Selected compounds...
Brain metastases (BMs) are the most common and among deadliest brain tumors. Currently, there no reliable predictors of BM development from primary cancer, which limits early intervention. Lung adenocarcinoma (LUAD) is source here we obtained 402 tumor plasma samples a large cohort patients with LUAD or without (n = 346). DNA methylation signatures were evaluated to build validate an accurate model predicting LUAD, was integrated clinical factors provide comprehensive patient-specific risk...
The ability of a patient tumor to engraft an immunodeficient mouse is the strongest known independent indicator poor prognosis in early-stage non-small cell lung cancer (NSCLC). Analysis primary NSCLC proteomes revealed low-level expression mitochondrial aconitase (ACO2) more aggressive, engrafting tumors. Knockdown ACO2 protein transformed immortalized epithelial cells, whereas upregulation cells inhibited proliferation vitro and growth vivo. High level increased iron response element...
Abstract Comprehensive N6-methyladenosine (m6A) epitranscriptomic profiling of primary tumors remains largely uncharted. Here, we profiled the m6A epitranscriptome 10 nonneoplastic lung tissues and 51 adenocarcinoma (LUAD) tumors, integrating corresponding transcriptomic, proteomic, extensive clinical annotations. We identified distinct clusters genes that were exclusively linked to disease progression through modifications. In comparison with tissues, 430 transcripts be hypo-methylated 222...
<p>Supplementary Figure S2 shows the chemical stability of FD1 (ZD06519)</p>
<p>Supplementary Figure S3 shows the in vitro cytotoxicity assessment of trastuzumab-ADCs both two-dimensional (2D) and three-dimensional (3D) spheroid assays</p>
<p>Synthesis and characterization of free drugs drug-linkers</p>
<p>Supplementary Figure S4 shows the pharmacokinetic analysis of ADCs (total antibody PK) from tolerability study in rats</p>
<p>Supplementary Figure S4 shows the pharmacokinetic analysis of ADCs (total antibody PK) from tolerability study in rats</p>
<p>Synthesis and characterization of free drugs drug-linkers</p>
<p>HPLC-HIC, LC-MS, HPLC-SEC, residual free drug analysis, and endotoxin levels of ADCs</p>
<div>Abstract<p>In recent years, the field of antibody drug conjugates (ADC) has seen a resurgence, largely driven by clinical benefit observed in patients treated with ADCs incorporating camptothecin-based topoisomerase I inhibitor payloads. Herein, we present development novel camptothecin ZD06519 (FD1), which been specifically designed for its application as an ADC payload. A panel analogs different substituents at C-7 and C-10 positions core was prepared tested <i>in...
<p>Supplementary Figure S3 shows the in vitro cytotoxicity assessment of trastuzumab-ADCs both two-dimensional (2D) and three-dimensional (3D) spheroid assays</p>
<p>Supplementary Figure S1 shows the murine plasma stability of T-DL4 and T-DL13</p>
<p>Supplementary Figure S1 shows the murine plasma stability of T-DL4 and T-DL13</p>
<div>Abstract<p>In recent years, the field of antibody drug conjugates (ADC) has seen a resurgence, largely driven by clinical benefit observed in patients treated with ADCs incorporating camptothecin-based topoisomerase I inhibitor payloads. Herein, we present development novel camptothecin ZD06519 (FD1), which been specifically designed for its application as an ADC payload. A panel analogs different substituents at C-7 and C-10 positions core was prepared tested <i>in...
<p>HPLC-HIC, LC-MS, HPLC-SEC, residual free drug analysis, and endotoxin levels of ADCs</p>
<p>Supplementary Figure S2 shows the chemical stability of FD1 (ZD06519)</p>
<div>Abstract<p>Comprehensive N<sup>6</sup>-methyladenosine (m<sup>6</sup>A) epitranscriptomic profiling of primary tumors remains largely uncharted. Here, we profiled the m<sup>6</sup>A epitranscriptome 10 nonneoplastic lung tissues and 51 adenocarcinoma (LUAD) tumors, integrating corresponding transcriptomic, proteomic, extensive clinical annotations. We identified distinct clusters genes that were exclusively linked to disease progression...