A5058353577- Cancer Genomics and Diagnostics
- Radiation Therapy and Dosimetry
- Molecular Biology Techniques and Applications
- Advanced Radiotherapy Techniques
- CRISPR and Genetic Engineering
- Nanoplatforms for cancer theranostics
- Genetic factors in colorectal cancer
- Advanced biosensing and bioanalysis techniques
- Medical Imaging Techniques and Applications
- DNA Repair Mechanisms
- Radiopharmaceutical Chemistry and Applications
- BRCA gene mutations in cancer
- Radiation Effects and Dosimetry
- Gene expression and cancer classification
- Radiation Dose and Imaging
- Single-cell and spatial transcriptomics
- Nuclear Physics and Applications
- Lung Cancer Treatments and Mutations
- Electron Spin Resonance Studies
- Breast Cancer Treatment Studies
- Radiation Detection and Scintillator Technologies
- Epigenetics and DNA Methylation
- Genomic variations and chromosomal abnormalities
- PARP inhibition in cancer therapy
- Advanced Breast Cancer Therapies
Dana-Farber Cancer Institute
2016-2025
Dana-Farber Brigham Cancer Center
2016-2025
Brigham and Women's Hospital
2016-2025
Harvard University
2016-2025
Broad Institute
2020-2025
Boston University
2008-2023
Dana-Farber/Harvard Cancer Center
2018
University of Massachusetts Lowell
2015
Northeastern University
2015
Woman's Hospital
2014-2015
Abstract Purpose: Existing cell-free DNA (cfDNA) methods lack the sensitivity needed for detecting minimal residual disease (MRD) following therapy. We developed a test tracking hundreds of patient-specific mutations to detect MRD with 1,000-fold lower error rate than conventional sequencing. Experimental Design: compared our approach digital droplet PCR (ddPCR) in dilution series, then retrospectively identified two cohorts patients who had undergone prospective plasma sampling and clinical...
The bystander effect, originating from cells irradiated in vitro , describes the biologic response(s) of surrounding not directly targeted by a radiation insult. To overcome limitations tissue culture models and determine whether effect that is initiated vivo decay radionuclide can be demonstrated an animal, ability 5-[ 125 I]iodo-2′-deoxyuridine ( IUdR)-labeled tumor to exert damaging on neighboring unlabeled growing s.c. nude mice has been investigated. When are injected with mixture human...
More than 50% of all cancer patients receive radiation therapy. The clinical delivery curative dose is strictly restricted by the proximal healthy tissues. We propose a dual-targeting strategy using vessel-targeted-radiosensitizing gold nanoparticles and conformal-image guided therapy to specifically amplify damage in tumor neoendothelium. resulting vascular disruption substantially improved therapeutic outcome subsidized radiation/nanoparticle toxicity, extending its utility intransigent or...
Radiation therapy (RT), a critical modality in the treatment of lung cancer, induces direct tumor cell death and augments tumor-specific immunity. However, despite initial control, most patients suffer from locoregional relapse and/or metastatic disease following RT. The use immunotherapy non-small-cell cancer (NSCLC) could potentially change this outcome by enhancing effects Here, we report significant (up to 70% volume reduction target lesion) durable 12 weeks) regressions conditional...
Abstract Detecting mutations from single DNA molecules is crucial in many fields but challenging. Next-generation sequencing (NGS) affords tremendous throughput cannot directly sequence double-stranded (‘single duplexes’) to discern the true on both strands. Here we present Concatenating Original Duplex for Error Correction (CODEC), which confers duplex resolution NGS. CODEC 1,000-fold higher accuracy than NGS, using up 100-fold fewer reads sequencing. revealed mutation frequencies of 2.72 ×...
Minimally invasive molecular profiling using cell-free DNA (cfDNA) is increasingly important to the management of cancer patients; however, low sensitivity remains a major limitation, particularly for brain tumor patients. Transiently attenuating cfDNA clearance from body-thereby, allowing more be sampled-has been proposed improve performance liquid biopsy diagnostics. However, there paucity clinical data on effect higher recovery. Here, we investigated impact collecting greater quantities...
Identifying low-abundance mutations within wild-type DNA is important in several fields of medicine, including cancer, prenatal diagnosis and infectious diseases. However, utilizing the clinical diagnostic potential rare limited by sensitivity molecular techniques employed, especially when type position are unknown. We have developed a novel platform that incorporates synthetic reference sequence polymerase chain reaction (PCR) reaction, designed to enhance amplification unknown mutant...
In this study, we quantify the relative damage enhancement due to presence of gold nanoparticles (GNP) in vitro a clinical 6 MV beam for various delivery parameters and depths. It is expected that depths modes produce larger proportions low-energy photons will have effect on cell samples containing GNP. HeLa cells with without 50 nm GNP were irradiated at 1.5, 5, 10, 15 20 cm. Conventional beams square aperture sizes 10 cm isocenter, flattening filter free (FFF) used. Relative DNA was...
Presence of excess unaltered, wild-type (WT) DNA providing no information biological or clinical value often masks rare alterations containing diagnostic therapeutic clues in cancer, prenatal diagnosis, infectious diseases organ transplantation. With the surge high-throughput technologies there is a growing demand for removing unaltered over large pools-of-sequences. Here we present nuclease-assisted minor-allele enrichment with probe-overlap (NaME-PrO), single-step approach broad genome...
The toxic effects of the short-lived (T 1/2 = 13.2 h) Auger-electron-emitting isotope 123I, incorporated in form 123IUdR into DNA V79 cells vitro, have been investigated and compared to those 125IUdR. For concentrations tested, rate incorporation at any time is proportional concentration extracellular radioactivity. curve for survival clonogenic decreases exponentially exhibits no shoulder low doses. mean lethal dose (D37) nucleus 79 +/- 9 cGy about same as that obtained previously with...
Despite widespread interest in next-generation sequencing (NGS), the adoption of personalized clinical genomics and mutation profiling cancer specimens is lagging, part because technical limitations. Tumors are genetically heterogeneous often contain normal/stromal cells, features that lead to low-abundance somatic mutations generate ambiguous results or reside below NGS detection limits, thus hindering sensitivity/specificity standards calling. We applied COLD-PCR (coamplification at lower...
We report the design and fabrication of third generation ultrasmall PEGylated gold nanoparticles based platform (AuRad™) optimized for applications in radiation therapy. The AuRad™ nanoplatform has following key features: (I) surface coating hetero-bifunctional-PEG with amine, carboxyl, methoxy functional groups, which make this a versatile to conjugate various moieties like fluorophores, peptides, drugs, radiolabels; (II) size that is longer circulation, higher tumor uptake modulated...
Allele-specific polymerase chain reaction (PCR) (amplification-refractory mutation system, ARMS) is one of the most commonly used methods for detection. However, a main limitation ARMS-PCR false positive results obtained due to nonspecific priming that can take place with wild-type (WT) DNA, which often precludes detection low-level mutations. To improve analytical specificity ARMS, we present here new technology, NAPA: NaME-PrO-assisted overcomes ARMS deficiency by adding brief enzymatic...
Abstract Purpose While circulating tumor DNA (ctDNA) is a promising biomarker for minimal residual disease (MRD) detection in head and neck squamous cell carcinoma (HNSCC), more sensitive assays are needed accurate MRD at clinically-relevant timepoints. Ultrasensitive immediately after surgery could guide adjuvant therapy decisions, but early ctDNA dynamics poorly understood. Experimental Design We applied MAESTRO, whole-genome, tumor-informed, mutation-enrichment sequencing assay, pooled...