A5001466446- Cancer Immunotherapy and Biomarkers
- Acute Myeloid Leukemia Research
- Pancreatic and Hepatic Oncology Research
- Immunotherapy and Immune Responses
- interferon and immune responses
- Ferroptosis and cancer prognosis
- Immune cells in cancer
- Cancer Cells and Metastasis
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Hematopoietic Stem Cell Transplantation
- Cancer, Hypoxia, and Metabolism
- Neuroblastoma Research and Treatments
- Anesthesia and Pain Management
- Chronic Myeloid Leukemia Treatments
- Adenosine and Purinergic Signaling
- Mesenchymal stem cell research
- Cancer Research and Treatments
- Pediatric Pain Management Techniques
- Multiple Myeloma Research and Treatments
- Hematological disorders and diagnostics
- Effects of Radiation Exposure
- Cancer, Stress, Anesthesia, and Immune Response
- CAR-T cell therapy research
- Cytokine Signaling Pathways and Interactions
- 3D Printing in Biomedical Research
University of Rochester Medical Center
2022-2025
University of Rochester
2021-2025
Background/Objectives: Pancreatic ductal adenocarcinoma (PDAC), expecting to be the second leading cause of cancer deaths by 2030, resists immune checkpoint therapies due its immunosuppressive tumor microenvironment (TME). Leukemia inhibitory factor (LIF) is a key target in PDAC, promoting stemness, epithelial-mesenchymal transition (EMT), and therapy resistance. Phase 1 clinical trials showed anti-LIF safe but with limited efficacy, suggesting better outcomes when combined chemotherapy,...
Background: Standard of care therapies such as radiotherapy and chemotherapy have shown little efficacy against pancreatic ductal adenocarcinoma (PDAC). Immunotherapy is a newly emerging form treatment that has promise; however, toxic systemic effects resulted in limited use the clinic. Shifting from to local delivery cancer therapeutics reduces adverse increases response rates multiple malignancies. Importantly, tumor-targeted on distal tissues, bone marrow, not been thoroughly...
Radiation is used to treat pancreatic ductal adenocarcinoma (PDAC) in the locally-advanced setting. Stereotactic body radiation therapy (SBRT), particular, has shown improved outcomes against conventional RT a number of clinical trials. One key cell type involved response are neutrophils. These innate immune cells first responders tissue damage and infiltrate irradiated tumors high numbers rectify injury. Neutrophils typically possess an immunosuppressive, wound healing phenotype this...
Hematopoiesis takes place in the bone marrow and is supported by a complex cellular molecular network microenvironment. Commonly used models of human microenvironment include murine two-dimensional three-dimensional tissue cultures. While these model systems have led to critical advances field, they fail recapitulate many aspects marrow. This has limited our understanding pathophysiology deficiencies therapy for pathologies such as failure syndromes leukemias. Therefore, we developed modular...
Background Stereotactic body radiotherapy (SBRT) induces immunogenic cell death, leading to subsequent antitumor immune response that is in part counterbalanced by activation of evasive processes, for example, upregulation programmed death-ligand 1 (PD-L1) and adenosine generating enzyme, CD73. CD73 upregulated pancreatic ductal adenocarcinoma (PDAC) compared with normal tissue high expression PDACs associated increased tumor size, advanced stage, lymph node involvement, metastasis, PD-L1...
Abstract Leukemias are challenging diseases to treat due, in part, interactions between leukemia cells and the bone marrow microenvironment (BMME) that contribute significantly disease progression. Studies have shown leukemic secrete C‐chemokine (C‐C motif) ligand 3 (CCL3), disrupt BMME resulting loss of hematopoiesis support cell survival proliferation. In this study, a murine model blast crisis chronic myelogenous (bcCML) expresses translocation products BCR/ABL Nup98/HoxA9 was used...
Abstract Rectal cancer ranks as the second leading cause of cancer-related deaths. Neoadjuvant therapy for rectal patients often results in individuals that respond well to and those poorly, requiring life-altering excision surgery. It is inadequately understood what dictates this responder/nonresponder divide. Our major aim identify factors tumor microenvironment drive a fraction radiotherapy. We also sought distinguish potential biomarkers would indicate positive response design...
<h3>Background</h3> Colorectal Cancer (CRC) is a devastating malignancy that ranks as the second leading cause of cancer-related deaths. Rectal cancer (RC) comprises one-third CRC cases, with over 50,000 people in US diagnosed each year. Short course radiation therapy (SCRT) being investigated curative treatment option for RC, aim to preserve organ function and avoid life-altering excision surgery. SCRT can significantly reduce tumor burden subset patients, however most patients' tumors do...
The immunosuppressive milieu in pancreatic cancer (PC) is a significant hurdle to treatments, resulting survival statistics that have barely changed 5 decades. Here we present combination treatment consisting of stereotactic body radiation therapy (SBRT) and IL-12 mRNA lipid nanoparticles delivered directly murine tumors. This was effective against primary metastatic models, achieving cures both settings. protein concentrations were transient localized primarily the tumor. Depleting CD4 CD8...
Abstract Rectal cancer ranks as the second leading cause of cancer-related deaths. Neoadjuvant therapy for rectal patients often results in individuals that respond well to and those poorly, requiring life-altering excision surgery. It is inadequately understood what dictates this responder/nonresponder divide. Our major aim identify factors tumor microenvironment drive a fraction radiotherapy. We also sought distinguish potential biomarkers would indicate positive response design...
Interactions between acute myeloid leukemia (AML) and the bone marrow microenvironment (BMME) are critical to progression chemoresistance. In solid tumor microenvironment, altered metabolite levels contribute cancer progression. We performed a metabolomic analysis of AML patient serum, revealing increased metabolites compared age- sex-matched controls. The most highly elevated in BMME was lactate. Lactate signaling tumors induces immunosuppressive tumor-associated macrophages correlates with...