A5003082907- Nanoplatforms for cancer theranostics
- Mast cells and histamine
- Cellular Mechanics and Interactions
- SARS-CoV-2 and COVID-19 Research
- Cancer Immunotherapy and Biomarkers
- 3D Printing in Biomedical Research
- CAR-T cell therapy research
- Nanoparticle-Based Drug Delivery
- Cancer Cells and Metastasis
- Ultrasound and Hyperthermia Applications
- RNA Interference and Gene Delivery
- COVID-19 Clinical Research Studies
- Photoacoustic and Ultrasonic Imaging
- Immune Cell Function and Interaction
- Immune cells in cancer
- Hydrogels: synthesis, properties, applications
- Immunotherapy and Immune Responses
- Mathematical Biology Tumor Growth
- Advanced Polymer Synthesis and Characterization
- COVID-19 epidemiological studies
- Cancer, Hypoxia, and Metabolism
- Elasticity and Material Modeling
- Fibroblast Growth Factor Research
- Proteoglycans and glycosaminoglycans research
- Vaccine Coverage and Hesitancy
University of Cyprus
2016-2025
Massachusetts General Hospital
2022-2024
Harvard University
2022-2024
Advances in immunotherapy have revolutionized the treatment of multiple cancers. Unfortunately, tumors usually impaired blood perfusion, which limits delivery therapeutics and cytotoxic immune cells to also results hypoxia-a hallmark abnormal tumor microenvironment (TME)-that causes immunosuppression. We proposed that normalization TME using antiangiogenic drugs and/or mechanotherapeutics can overcome these challenges. Recently, with checkpoint blockers was shown effectively induce vascular...
Tumor normalization strategies aim to improve tumor blood vessel functionality (i.e., perfusion) by reducing the hyper-permeability of vessels or restoring compressed vessels.Despite progress in normalize microenvironment (TME), their combinatorial antitumor effects with nanomedicine and immunotherapy remain unexplored.Methods: Here, we re-purposed TGF-β inhibitor tranilast, an approved anti-fibrotic antihistamine drug, combined it Doxil TME, increase perfusion oxygenation, enhance...
Normalization of the tumor microenvironment by selectively targeting components extracellular matrix has been recently proposed to have potential decompress blood vessels, increase vessel perfusion and thus, improve drug delivery efficacy cancer therapy. Therefore, we now need identify safe well tolerated pharmaceutical agents that are able remodel solid tumors enhance chemotherapy. In this study, repurposed Pirfenidone, a clinically approved anti-fibrotic for treatment idiopathic pulmonary...
Dexamethasone is a glucocorticoid steroid with anti-inflammatory properties used to treat many diseases, including cancer, in which it helps manage various side effects of chemo-, radio-, and immunotherapies. Here, we investigate the tumor microenvironment (TME)-normalizing dexamethasone metastatic murine breast cancer (BC). normalizes vessels extracellular matrix, thereby reducing interstitial fluid pressure, tissue stiffness, solid stress. In turn, penetration 13 32 nm dextrans, represent...
Abstract Accumulation of mechanical stresses during cancer progression can induce blood and lymphatic vessel compression, creating hypo-perfusion, hypoxia interstitial hypertension which decrease the efficacy chemo- nanotherapies. Stress alleviation treatment has been recently proposed to reduce in order decompress tumor vessels improve perfusion chemotherapy. However, it remains unclear if improves nanomedicines, present numerous advantages over traditional chemotherapeutic drugs....
Despite the important role that mechanical forces play in tumor growth and therapy, contribution of swelling to mechanopathology remains unexplored. Tumors rich hyaluronan exhibit a highly negative fixed charge density. Repulsive among these charges as well cancer cells due regulation intracellular tonicity can cause development stress might compress blood vessels, compromising perfusion drug delivery. Here, we designed an experimental strategy, using four orthotopic models, measure related...
Mechanical forces play a crucial role in tumor patho-physiology. Compression of cancer cells inhibits their proliferation rate, induces apoptosis and enhances invasive metastatic potential. Additionally, compression intratumor blood vessels reduces the supply oxygen, nutrients drugs, affecting progression treatment. Despite great importance mechanical microenvironment to pathology cancer, there are limited studies for constitutive modeling properties tumors on how these parameters affect...
Abstract Nano‐immunotherapy regimens have high potential to improve patient outcomes, as already demonstrated in advanced triple negative breast cancer with nanoparticle albumin‐bound paclitaxel and the immune checkpoint blocker (ICB) atezolizumab. This regimen, however, does not lead cures median survival lasting less than two years. Thus, understanding mechanisms of resistance development strategies enhance nano‐immunotherapy are urgently needed. Here, human tissue it is shown that blood...
Significance Vessel cooption is a strategy that many tumors employ to progress without creating new blood vessels but by exploiting preexisting of the host tissue. In addition promoting tumor growth, also associated with resistance antiangiogenic therapy. Despite importance this mode progression, molecular and cellular mechanisms are not fully understood. Here, we combine intravital microscopy imaging mathematical modeling explore dynamics individual cancer cell collective response coopted...
Abstract Nano-immunotherapy improves breast cancer outcomes but not all patients respond and none are cured. To improve efficacy, research focuses on drugs that reprogram cancer-associated fibroblasts (CAFs) to therapeutic delivery immunostimulation. These drugs, however, have a narrow window cause adverse effects. Developing strategies increase CAF-reprogramming while limiting effects is urgent. Here, taking advantage of the capabilities tranilast, we developed tranilast-loaded micelles....
Nanomedicine offered hope for improving the treatment of cancer but survival benefits clinically approved nanomedicines are modest in many cases when compared to conventional chemotherapy. Metronomic therapy, defined as frequent, low dose administration chemotherapeutics - is being tested clinical trials an alternative maximum tolerated (MTD) chemotherapy schedule. Although metronomic has not been yet, it shown better than MTD preclinical studies. When beneficial, therapy seems be associated...
Immunotherapy has revolutionized the treatment of dozens cancers and became a standard care for some tumor types. However, majority patients do not benefit from current immunotherapeutics many develop severe toxicities. Therefore, identification biomarkers to classify as likely responders or non-responders immunotherapy is timely task. Here, we test ultrasound imaging markers stiffness perfusion. Ultrasound non-invasive clinically available can be used both perfusion evaluation. In this...
Abstract Purpose: To explore the cellular cross-talk of tumor-resident mast cells (MC) in controlling activity cancer-associated fibroblasts (CAF) to overcome tumor microenvironment (TME) abnormalities, enhancing efficacy immune-checkpoint inhibitors sarcoma. Experimental Design: We used a coculture system followed by further validation mouse models fibrosarcoma and osteosarcoma with or without administration MC stabilizer antihistamine ketotifen. evaluate contribution ketotifen sensitizing...
Hyaluronan is abundant in the extracellular matrix of many desmoplastic tumors and determines large part tumor biochemical mechanical microenvironment. Additionally, it has been identified as one major physiological barriers to effective delivery drugs solid its targeting with use pharmaceutical agents shown decompress blood vessels, thus improve perfusion efficacy cytotoxic drugs. In this study, we investigated contribution hyaluronan accumulation forces tumors. Using experimental data from...
Significance A distinctive feature of COVID-19 is its extreme heterogeneity—illness ranges from minimally symptomatic to life threatening. Heterogeneity results a poorly understood combination patient factors, viral dynamics, antiviral and immune modulating therapies, dynamics the innate adaptive responses. In order better understand clinical heterogeneity optimal treatment, we developed comprehensive mathematical model incorporating elements responses, renin−angiotensin system (which virus...
SARS-CoV-2 vaccines are effective at limiting disease severity, but effectiveness is lower among patients with cancer or immunosuppression. Effectiveness wanes time and varies by vaccine type. Moreover, previously prescribed were based on the ancestral spike-protein that emerging variants may evade. Here, we describe a mechanistic mathematical model for vaccination-induced immunity. We validate it available clinical data use to simulate of against viral antigenicity, increased virulence,...
The lack of properly perfused blood vessels within tumors can significantly hinder the distribution drugs, leading to reduced treatment effectiveness and having a negative impact on quality life patients with cancer. This problem is particularly pronounced in desmoplastic cancers, where interactions between cancer cells, stromal fibrotic matrix lead tumor stiffness compression most tumor. To address this issue, two mechanotherapy approaches-mechanotherapeutics ultrasound sonopermeation-have...
Amphiphilic polymer conetworks are cross-linked polymers that swell both in water and organic solvents can phase separate on the nanoscale bulk or selective solvents. To date, however, this separation has only been reported with short-range order, characterized by disordered morphologies. We now report first example of amphiphilic conetworks, based end-linked "core-first" star block copolymers, form a lamellar long-range order. These mesoscopically ordered systems be produced simple fashion...
Mechanical compression is a common abnormality of brain tumors that has been shown to be responsible for the severe neurological defects cancer patients representing negative prognostic factor. Indeed, it note undergo resection exhibited higher survival rates than those subjected biopsy only, suggesting compressive forces generated during tumor growth play key role in progression. Despite importance mechanical tumors, there lack studies examining its direct effects on cells and mechanisms...
Ongoing research is actively exploring the use of immune checkpoint inhibitors to treat solid tumors by inhibiting PD-1/PD-L1 axis and reactivating function cytotoxic T effector cells. Many types tumors, however, are characterized a dense stiff stroma difficult treat. Mechanotherapeutics have formed recent class drugs that aim restore biomechanical abnormalities tumor microenvironment, related increased stiffness hypo-perfusion. Here, we developed polymeric formulation containing...
In the pursuit of advancing cancer therapy, this study explores predictive power machine learning in analyzing tumor characteristics, specifically focusing on effects stiffness and perfusion (i.e., blood flow) treatment efficacy. Recent advancements oncology have highlighted significance these physiological properties microenvironment determining outcomes. We delve into relationship between attributes effectiveness therapies preclinical models. Utilizing robust statistical methods...