A5006411392- Palliative Care and End-of-Life Issues
- Organ Donation and Transplantation
- Radiomics and Machine Learning in Medical Imaging
- Ethics in Clinical Research
- Patient Dignity and Privacy
- Cancer Genomics and Diagnostics
- Lung Cancer Diagnosis and Treatment
- Cancer Immunotherapy and Biomarkers
- Cancer Research and Treatments
- Ethics in medical practice
- Radiopharmaceutical Chemistry and Applications
- Acute Lymphoblastic Leukemia research
- Patient-Provider Communication in Healthcare
- Peptidase Inhibition and Analysis
- Lung Cancer Treatments and Mutations
- Childhood Cancer Survivors' Quality of Life
- CRISPR and Genetic Engineering
- Health Systems, Economic Evaluations, Quality of Life
- Family Support in Illness
- Biomedical Ethics and Regulation
- PARP inhibition in cancer therapy
- Advanced biosensing and bioanalysis techniques
- Adolescent and Pediatric Healthcare
- Esophageal Cancer Research and Treatment
- Radiation Therapy and Dosimetry
Tango Therapeutics (United States)
2025
Moores Cancer Center
2022
University of California, San Diego
2022
University of South Florida
2018
Moffitt Cancer Center
2010-2018
Oregon State University
1987
The NCCN Guidelines for Lung Cancer Screening recommend criteria selecting individuals screening and provide recommendations evaluation follow-up of lung nodules found during initial subsequent screening. These Insights focus on recent updates to the Screening.
Abstract Synthetic lethality approaches in BRCA1/2-mutated cancers have focused on poly(ADP-ribose) polymerase (PARP) inhibitors, which are subject to high rates of innate or acquired resistance patients. Here, we used CRISPR/Cas9-based screening identify DNA Ligase I (LIG1) as a novel target for synthetic BRCA1-mutated cancers. Publicly available data supported LIG1 hyperdependence BRCA1-mutant cells across variety breast and ovarian cancer cell lines. We CRISPRn, CRISPRi, RNAi, protein...
Abstract Inhibition of the deubiquitinating enzyme USP1 can induce synthetic lethality in tumors characterized by homologous recombination deficiency (HRD) and represents a novel therapeutic strategy for treatment BRCA1/2 mutant cancers, potentially including patients whose have primary or acquired resistance to PARP inhibitors (PARPi). Here, we present comprehensive characterization TNG348, an allosteric, selective, reversible inhibitor (USP1i). TNG348 induces dose-dependent accumulation...
<p>Perturbation of LIG1 induces proportional PAR accumulation in BRCA1-mutated cells immunofluorescence and in-cell western assay formats. A) In-cell Western blotting on treatment day 4 MDA-MB-436 engineered to express a DOX-inducible cDNA with endogenous knockout. B) Model validation blotting. C) Quantification relative NAD+ as deduced by total NAD (NADt)/NADH ratio normalized +DOX condition (t-test sgLIG1 vs. -DOX p < 0.0001).</p>
<div>Abstract<p>Synthetic lethality approaches in <i>BRCA1/2-</i>mutated cancers have focused on PARP inhibitors, which are subject to high rates of innate or acquired resistance patients. In this study, we used CRISPR/Cas9-based screening identify DNA ligase I (LIG1) as a novel target for synthetic <i>BRCA1-</i>mutated cancers. Publicly available data supported <i>LIG1</i> hyperdependence <i>BRCA1</i> mutant cells across variety...
<p>Cell lines with damaging mutations in BRCA2 are dependent on LIG1. A) Analysis of DepMap data (28) comparing LIG1 dependence cell vs. wild-type lines. ***p=0.0004 unpaired t-test. B,C) Representative image (B) and quantification (C) colony formation assay DLD1 (WT) BRCA2-/- cells transfected siRNAs targeting the gene or a control sequence. D,E) (D) (E) Western blot assessing knockdown at endpoint for (B).</p>
<p>CRISPRi system does not reduce viability of BRCA mutant cells using an intron-targeting control guide RNA (sgITC). Representative image (A) and quantification (B) colony formation assay (treatment day 14) in MDA-MB-436 (BRCA1 mutant) engineered to express a DOX-inducible CRISPRi targeting intron Knockdown was validated by Western blot (representative C, D). FC, fold-change.</p>
<p>Withdrawal of Doxycycline leads to LIG1 depletion that is sustained through the study. Image (A) and quantification (B) western blotting data from tumors immunodeficient mice grafted with MDA-MB-436 cells engineered express a DOX-inducible CRISPR-resistant cDNA endogenous knockout. Samples depicted are endpoint (day 29 post-grouping).</p>
<p>LIG1 inactivation is lethal in HRD+ BRCA1/2 wild-type HCC1806 cells. A) Representative colony formation assay (treatment day 11) using DOX-inducible shRNA against LIG1, PLK1 (pan-lethal control), or a control sequence B) Western blots assessing LIG1 protein level the models from (A) 4).</p>
<p>LIG1 inactivation is lethal in BRCA1-mutant MDA-MB-436 cells, and rescued by exogenous expression of wild-type BRCA1. A) Representative colony formation assay (treatment day 14) using DOX-inducible shRNA against LIG1, PLK1 (pan-lethal control), or a control sequence cells stably infected with cDNA encoding BRCA1 vector. B) Model validation Western blotting. C) blots assessing LIG1 protein level at endpoint.</p>
<p>Quantification of western blots for dTAG-mediated LIG1 degradation. MDA-MB-436 cells were engineered to express a CRISPR-resistant cDNA fused either the FKBP12mut (dTAG) degron (degradable) (A) or FKBP12wt (non-degradable) (B), with knockout endogenous LIG1. Cells then treated 4 days vehicle (DMSO) indicated doses VHL-targeting PROTAC dTAGv1 and subject immunoblotting LIG1, HA tag, loading control. FC, fold-change.</p>
<p>Supplementary Materials</p>
The ethical concerns in statements of 116 family caregivers to dementia patients were identified. Concerns included obligations for caregiving; conflicts with responsibilities family, career or personal well-being; financing health care; standards and patient roles planning care. These are related societal allocation resources care, the principle autonomy, several other issues.
In preparation for the development of a rapid tissue donation (RTD) programme, we surveyed healthcare providers (HCPs) in our institution about knowledge and attitudes related to RTD with lung cancer patients. A 31-item web based survey was developed collecting data on demographics, RTD. The contained three items measuring participants' RTD, five assessing towards recruitment six HCPs' level agreement factors influencing decisions discuss Response options were presented 5-point Likert scale....
Abstract Background: Translational research in advanced lung cancer is hindered by the limited availability of specimens for molecular techniques. Although helpful, standard practice to biopsy a small amount tissue from single site provides information. We launched thoracic rapid donation (RTD) program enable with collection at multiple tumor sites within hours after death. Many patients chose enroll RTD as an opportunity contribute research. will support projects, such studying differential...