A5085506831- Nanoplatforms for cancer theranostics
- Immunotherapy and Immune Responses
- Cancer Immunotherapy and Biomarkers
- Cancer Cells and Metastasis
- Cancer Research and Treatments
- Single-cell and spatial transcriptomics
- bioluminescence and chemiluminescence research
- Cancer Genomics and Diagnostics
- Virus-based gene therapy research
- Cancer Risks and Factors
- Cell Image Analysis Techniques
- Advanced Breast Cancer Therapies
- CAR-T cell therapy research
- Immune cells in cancer
- Inflammatory Biomarkers in Disease Prognosis
- Extracellular vesicles in disease
- Molecular Biology Techniques and Applications
- Angiogenesis and VEGF in Cancer
- Lung Cancer Research Studies
- Atherosclerosis and Cardiovascular Diseases
- Gene expression and cancer classification
- Prostate Cancer Treatment and Research
- Inflammatory mediators and NSAID effects
- Cancer, Stress, Anesthesia, and Immune Response
- Microbial metabolism and enzyme function
Celldex Therapeutics (United States)
2023-2025
Brigham and Women's Hospital
2020-2024
Harvard University
2018-2024
Soochow University
2022
Second Affiliated Hospital of Soochow University
2022
Oregon Health & Science University
2015-2021
University of Colorado Anschutz Medical Campus
2014
University of Science and Technology of China
2012
Breast involution following pregnancy has been implicated in the high rates of metastasis observed postpartum breast cancers; however, it is not clear how this remodeling process promotes metastasis. Here, we demonstrate that human cancers have increased peritumor lymphatic vessel density correlates with frequency lymph node metastases. Moreover, was normal tissue compared from nulliparous women. In rodents, mammary lymphangiogenesis upregulated during weaning-induced gland involution....
Normal epithelium exists within a dynamic extracellular matrix (ECM) that is tuned to regulate tissue specific epithelial cell function. As such, ECM contributes homeostasis, differentiation, and disease, including cancer. Though it now recognized the functional unit of normal transformed its adjacent ECM, we lack basic understanding tissue-specific composition abundance, as well how physiologic changes in impact cancer risk outcomes. While traditional proteomic techniques have advanced...
Women diagnosed with breast cancer within 5 years postpartum (PPBC) have poorer prognosis than age matched nulliparous women, even after controlling for clinical variables known to impact disease outcomes. Through rodent modeling, the poor of PPBC has been attributed physiologic mammary gland involution, which shapes a tumor promotional microenvironment through induction wound-healing-like programs including myeloid cell recruitment. Previous studies utilizing immune compromised mice shown...
Women diagnosed with breast cancer within 5 years of childbirth have poorer prognosis than nulliparous or pregnant women. Weaning-induced involution is implicated, as the collagen-rich, immunosuppressive microenvironment involuting mammary gland tumor promotional in mice. To investigate role fibroblasts, isolated PDGFRα+ cells from and postweaning mice were assessed for activation phenotype protumorigenic function. Fibroblast during was evident by increased expression fibrillar collagens,...
Patients with metastatic cancer refractory to standard systemic therapies have a poor prognosis and few therapeutic options. Radiotherapy can shape the tumor microenvironment (TME) by inducing immunogenic cell death promoting recognition natural killer cells T lymphocytes. Granulocyte macrophage-colony stimulating factor (GM-CSF) was known promote dendric maturation function, might also induce macrophage polarization anti-tumor capabilities. A phase II trial (ChiCTR1900026175) conducted...
Abstract CAN-2409 is a replication-defective adenovirus that delivers the herpes simplex virus (HSV)-thymidine kinase gene to infected cells. Intratumoral administration of followed by prodrug results in formation toxic metabolite able induce immunogenic cell death, exposure tumor-associated antigens, and activation local systemic immune responses. We used dynamic labeling model with MC38 tumor cells implanted photoconvertible Kaede mice. Violet light was label microenvironment,...
<p>CAN-2409 + prodrug induces expansion of immune cells and neoantigen-specific T retained in tumors. <b>A,</b> Summary MC38 implanted subcutaneous on the flank C57BL/6 Kaede mice photoconverted by violet light exposure. <b>B,</b> Study timeline for experiments assessing effect CAN-2409 TME modulation photoconvertible mice. <b>C,</b> Representative flow cytometry plots showing KR<sup>+</sup> KG<sup>+</sup> expression...
<p>No significant changes of CD8<sup>+</sup> T cell in the dLN following CAN-2409 treatment. <b>A,</b> Quantification total tumor dLN. <b>B,</b> Representative flow cytometry plots for KG<sup>+</sup> and KR<sup>+</sup> populations cells quantification are shown <b>C</b> cells. <b>D,</b> Ki67<sup>+</sup> percentage KG<sup>+</sup>CD8<sup>+</sup>T <b>E,</b>...
<p>Supplemental Figure 5 shows the flow cytometry gating scheme applied to tumor-draining lymph node samples</p>
<div>Abstract<p>CAN-2409 is a replication-defective adenovirus that delivers the herpes simplex virus–thymidine kinase gene to infected cells. Intratumoral administration of CAN-2409, followed by prodrug, results in formation toxic metabolite able induce immunogenic cell death, exposure tumor-associated antigens, and activation local systemic immune responses. We used dynamic labeling model with MC38 tumor cells implanted photoconvertible Kaede mice. Violet light was label...
<p>CAN-2409 + prodrug treatment reinvigorates tumor-retained, exhausted CD8<sup>+</sup> T cells, and tumor-experienced which egress tumors, have enhanced functionality. The effect of CAN-2409 on terminal exhaustion cells was assessed in the tumor using CX3CR1 as a marker coupled with granzyme B expression. <b>A,</b> Representative flow cytometry plots for total, KG<sup>+</sup>, KR<sup>+</sup> populations total TAA-specific (MC38...
<p>CAN-2409 + prodrug inhibits tumor growth and increases lymphocyte infiltration in MC38 tumor–bearing C57BL/6 mice. <b>A,</b> mice were treated with or without CAN-2409 i.t. (red arrow) followed by 4 days of i.p. administration (blue arrows), was monitored. Left, curves. Right, inhibition rate after treatment. <b>B,</b> Endpoint analysis mass. <b>C–G,</b> immune populations assessed flow cytometry. <i>N</i> = 7–9 per group (some tumors...
<p>Supplemental Figure 2 shows the tumor growth inhibition rate 4 days after treatment and immune cell quantification in tissue Kaede mice</p>
<p>Tumor growth was better controlled when CAN-2409 + prodrug treatment combined with anti–CTLA-4 antibody therapy compared alone. <b>A,</b> MC38 tumor–bearing mice were treated or without i.t. at day 10, followed by 4 days of i.p. administration prodrug. Anti–CTLA-4 isotype control on 13, and 16. Tumor monitored, tumors collected 17. <b>B,</b> weight quantification (left) tumor inhibition rate (right) study endpoint. Quantification CD3<sup>+</sup>...
<p>Supplemental Figure 4 shows the flow cytometry gating scheme applied to tumor samples</p>
<p>Tumor-recruited, tumor-retained, and tumor-experienced Tregs, which egress tumors, adopt an altered phenotype after CAN-2409 + prodrug treatment. The effect of treatment on proliferative status Treg cells was assessed using Ki67 as a marker coupled with the PD-1 expression. <b>A,</b> Representative flow cytometry plots for total, KG<sup>+</sup>, KR<sup>+</sup> cells. Quantification tumor experiencing (KR<sup>+</sup>) proliferation...
<p>Supplemental Figure 1 shows individual tumor growth of animals treated with and without CAN-2409 prodrug</p>
<p>Supplemental Figure 3 shows the combined effect of CAN-2409 and anti-CTLA-4 Ab treatment on individual tumor growth curves immune cell quantification in tissue</p>
<p>Expansion of immune cells within tumors is, in part, due to CAN-2409 + prodrug–mediated stimulation proliferation T-cell subsets the TME (total, neoantigen-specific, and stem-like CD8<sup>+</sup> T cells). <b>A,</b> The effect prodrug treatment on proliferative status was assessed using Ki67 as a marker. Representative flow cytometry plots for total, KG<sup>+</sup>, KR<sup>+</sup> populations TAA–specific (MC38...
Background: Recent studies have shown that the biological actions and toxicity of water-soluble compound, polyhydroxyfullerene (fullerenol), are related to concentrations present at a particular site action. This study investigated effects different fullerenol on cultured rat hippocampal neurons. Methods results: Fullerenol low significantly enhanced neuron viability as tested by MTT assay Hoechst 33342/propidium iodide double stain detection. At high concentrations, induced apoptosis...
Mammographically-detected breast density impacts cancer risk and progression, fibrillar collagen is a key component of density. However, physiologic factors influencing production in the are poorly understood. In female rats, we analyzed gene expression most abundantly expressed mammary collagens collagen-associated proteins across pregnancy, lactation, weaning cycle. We identified triphasic pattern regulation evidence for reproductive state-dependent composition. An initial phase deposition...
Abstract Programmed death ligand 1 (PD-L1) is an immune checkpoint protein that suppresses cytotoxic T lymphocytes and often overexpressed in cancers. Due to favorable clinical trial results, inhibition (ICI) part of Food Drug Administration approved immuno-oncology therapies; however, not all patients benefit from ICI therapy. High blood platelet-to-lymphocyte ratio has been associated with failure treatment, but whether platelets have a role hindering response unclear. Here, we report...
Despite abundant research demonstrating that platelets can promote tumor cell metastasis, whether primary tumors affect platelet-producing megakaryocytes remains understudied. In this study, we used a spontaneous murine model of breast cancer to show burden reduced megakaryocyte number and size disrupted polyploidization. Single-cell RNA sequencing demonstrated from tumor-bearing mice exhibit pro-inflammatory phenotype, epitomized by increased Ctsg, Lcn2, S100a8, S100a9 transcripts. Protein...