A5019688706- Cancer, Stress, Anesthesia, and Immune Response
- Immunotherapy and Immune Responses
- Cancer Immunotherapy and Biomarkers
- Immune cells in cancer
- Chemokine receptors and signaling
- Adipose Tissue and Metabolism
- Immune Cell Function and Interaction
- Receptor Mechanisms and Signaling
- CAR-T cell therapy research
- Hematopoietic Stem Cell Transplantation
- Heat shock proteins research
- Neuropeptides and Animal Physiology
- Stress Responses and Cortisol
- Cancer, Hypoxia, and Metabolism
- Thermal Regulation in Medicine
- thermodynamics and calorimetric analyses
- Exercise and Physiological Responses
- Advances in Oncology and Radiotherapy
- Nanoplatforms for cancer theranostics
- Thermoregulation and physiological responses
- Dietary Effects on Health
- Immune Response and Inflammation
- Epigenetics and DNA Methylation
- Melanoma and MAPK Pathways
- Cancer Risks and Factors
Roswell Park Comprehensive Cancer Center
2013-2025
Pennsylvania State University
2016-2023
Penn State Milton S. Hershey Medical Center
2016-2018
Hershey (United States)
2017
Significance We show that the mandated, subthermoneutral laboratory housing temperature, which is known to cause chronic, metabolic cold stress, induces suppression of antitumor immune response and promotes tumor growth metastasis. When mice are housed at thermoneutrality, there fewer immunosuppressive cells with significantly enhanced CD8 + T cell-dependent control growth. These findings underscore fact investigating mouse models under a single set environmental temperature conditions may...
The immune context of tumors has significant prognostic value and is predictive responsiveness to several forms therapy, including immunotherapy. We report here that CD8+ T-cell frequency functional orientation within the tumor microenvironment regulated by β2-adrenergic receptor (β-AR) signaling in host cells. used three strategies-physiologic (manipulation ambient thermal environment), pharmacologic (β-blockers), genetic (β2-AR knockout mice) reduce adrenergic stress two widely studied...
Cancer research relies heavily on murine models for evaluating the anti-tumour efficacy of therapies. Here we show that sensitivity several pancreatic tumour to cytotoxic therapies is significantly increased when mice are housed at a thermoneutral ambient temperature 30 °C compared with standard 22 °C. Further, find baseline levels norepinephrine as well anti-apoptotic molecules elevated in tumours from The also enhanced by administering β-adrenergic receptor antagonist These data...
Immunotherapy has expanded treatment options for cancers with historically poor outcomes, yet a significant proportion of patients still fail to achieve durable clinical benefit. We defined the contribution β-adrenergic receptor (βAR) signaling, component stress response, on success immunotherapy melanoma since use antagonists (β-blockers) is associated improved outcomes in some cancers. show that metastatic who received had overall survival if they also pan β-blockers. This retrospective...
There is a growing body of evidence supporting the synergistic roles radiotherapy and immunotherapy in treatment malignancy. Published case studies abscopal effect have been reported with use ipilimumab metastatic melanoma, but routine this combination therapy limited. We conducted retrospective analysis to evaluate patients treated for advanced melanoma at single institution from May 2011 June 2015. Patients were grouped into those who had received concurrent while on (Ipi-RT), did not....
Insulin-like growth factor 2 mRNA-binding proteins (IGF2BP1, IGF2BP2, and IGF2BP3) are a family of RNA-binding that play an essential role in the development disease by regulating mRNA stability translation critical regulators cell division metabolism. Genetic chemical inhibition these slows down cancer proliferation, decreases invasiveness, prolongs life span variety animal models. The induction tissues' immunogenicity is increasingly recognized, but, impact IGF2BPs on innate adaptive...
Purpose: Clinical trials combining hyperthermia with radiation and/or chemotherapy for cancer treatment have resulted in improved overall survival and control of local recurrences. The contribution thermally enhanced anti-immune function these effects is considerable interest, but not understood; studies on the fundamental elevated temperature immune effector cells are needed. goal this study to investigate potential mild impact tumour antigen-specific (Ag) CD8+ T cell functions.Method:...
The ability of dendritic cells (DCs) to stimulate and regulate T is critical effective anti-tumor immunity. Therefore, it important fully recognize any inherent factors which may influence DC function under experimental conditions, especially in laboratory mice since they are used so heavily model immune responses. goals this report 1) briefly summarize previous work revealing how DCs respond various forms physiological stress 2) present new data highlighting the potential for chronic mild...
Abstract Graft-versus-host disease (GVHD) is the major complication of allogeneic hematopoietic cell transplantation, a potentially curative therapy for hematologic diseases. It has long been thought that murine bone marrow–derived T cells do not mediate severe GVHD because their quantity and/or phenotype. During course experiments testing impact housing temperatures on GVHD, we discovered this apparent resistance function relatively cool ambient temperature. Murine have ability to in mice...
Background Presence of cytotoxic T lymphocytes (CTL) in the tumor microenvironment (TME) predicts effectiveness cancer immunotherapies. The ability toll-like receptor 3 (TLR3) ligands, interferons (IFNs) and COX2 inhibitors to synergistically induce CTL-attracting chemokines (but not regulatory cell (Treg)-attractants) TME, but healthy tissues, observed our preclinical studies, suggested that their systemic application can reprogram local TMEs. Methods Six evaluable patients (33–69 years)...
TPS319 Background: Immune checkpoint inhibitors (ICIs) have shown limited benefit in CRC outside the microsatellite instability high (MSI-H) population. Deficient cytotoxic T lymphocyte (CTL) trafficking to tumor microenvironment (TME) and excess pro-tumorigenic cytokines immunosuppressive cells may contribute primary ICI resistance stable (MSS) CRC. Selective enrichment of with specific chemokine receptors enhance antitumor immunity. Studies highlight role IL-12 improving progression-free...
The Marie Skłodowska-Curie Symposia on Cancer Research and Care (MSCS-CRC) promote collaborations between cancer researchers care providers in the United States, Canada Central Eastern European Countries (CEEC) to accelerate development of new therapies, strategies for early detection prevention, improve quality life patients their families. 4th MSCS-CRC (September 25-27, 2024, Buffalo New York) brought together 147 participants from US, Canada, Croatia, Czechia, Lithuania, Poland, Romania...
There is widespread recognition among both patients and caregivers that breast cancer often experience debilitating deficiencies in their ability to achieve thermal comfort, feeling excessively hot or cold under circumstances when others are comfortable. However, this symptom receives little clinical scientific attention beyond identification testing of drugs minimise menopausal-like symptoms. Could some these symptoms represent an important prognostic signal? discomfort be other...
Purpose: Researchers studying the murine response to stress generally use mice housed under standard, nationally mandated conditions as controls. Few investigators are concerned whether basic physical aspects of mouse housing could be an additional source stress, capable influencing subsequent impact experimentally applied stressor. We have recently become aware potential for important physiological and immunological properties in mice.Materials methods: Here we sought determine at standard...
Metastatic melanoma is a significant clinical problem with 5-year survival rate of only 15–20%. Recent approval new immunotherapies and targeted inhibitors have provided much needed options for these patients, in some cases promoting dramatic disease regressions. In particular, antibody-based therapies that block the PD-1/PD-L1 checkpoint inhibitory pathway achieved an increased overall response metastatic melanoma, yet durable rates are reported around 15%. To improve advanced-stage...
Traditional treatments, including a variety of thermal therapies have been known since ancient times to provide relief from rheumatoid arthritis (RA) symptoms. However, general absence information on how heating affects molecular or immunological targets relevant RA has limited heat treatment (HT) the category treatments as "alternative therapies". In this study, we evaluated effectiveness mild HT in collagen-induced (CIA) model which used many previous studies evaluate newer pharmacological...
The production of new blood cells relies on a hierarchical network hematopoietic stem and progenitor (HSPCs). To maintain lifelong hematopoiesis, HSPCs must be protected from ionizing radiation or other cytotoxic agents. For many years, murine models have been valuable source information regarding factors that either enhance reduce the survival after exposure marrow to radiation. In recent series studies, however, it has become clear housing-related such as cool room temperature required for...
Abstract Pre-clinical evaluation of novel therapies primarily relies on mouse models for predicting efficacy and toxicity. Unfortunately, when taken into the clinic, promising often fail to achieve expected results in patients or unexpected toxicities are encountered. Emerging evidence now suggests that laboratory housing conditions, including ad libitum feeding limited physical activity, can lead metabolic abnormalities which turn directly affect experimental outcomes diseases such as...