tumor-hypoxia-assessment-vivo-3d-oxygen-imaging-through-electron

Tumor Hypoxia Assessment: In Vivo 3D Oxygen Imaging Through Electron Paramagnetic Resonance

The precise and real-time measurement of oxygen partial pressure (pO2) brings valuable information in many pathologies, including cancer. Low tumor pO2 ...

Jagiellonian University

Cancer is one of the leading causes of death in humans. Despite the progress in cancer treatment, and an increase in the effectiveness of diagnostic methods, cancer is still highly lethal and very difficult to treat in many cases. Combination therapy, in the context of cancer treatment, seems to be a promising option that may allow minimizing treatment side effects and may have a significant impact on the cure. It may also increase the effectiveness of anti-cancer therapies. Moreover, combination treatment can significantly increase delivery of drugs to cancerous tissues. Photodynamic therapy and hyperthermia seem to be ideal examples that prove the effectiveness of combination therapy. These two kinds of therapy can kill cancer cells through different mechanisms and activate various signaling pathways. Both PDT and hyperthermia play significant roles in the perfusion of a tumor and the network of blood vessels wrapped around it. The main goal of combination therapy is to combine separate mechanisms of action that will make cancer cells more sensitive to a given therapeutic agent. Such an approach in treatment may contribute toward increasing its effectiveness, optimizing the cancer treatment process in the future.

Photodynamic Therapy and Hyperthermia in Combination Treatment-Neglected Forces in the Fight against Cancer.

The growing consumption of antidepressant pharmaceuticals has resulted in their widespread occurrence in the environment, particularly in waterways with a typical concentration range from ng L to μg L. An increasing number of studies have confirmed the ecotoxic potency of antidepressants, not only at high concentrations but also at environmentally relevant levels. The present review covers literature from the last decade on the individual-level ecotoxicological effects of the most commonly used antidepressants, including their impact on behavior, growth, and survival. We focus on the relationship between antidepressants physico-chemical properties and dynamics in the environment. Furthermore, we discuss the advantages of considering behavioral changes as sensitive endpoints in ecotoxicology, as well as some current methodological shortcomings in the field, including low standardization, reproducibility and context-dependency.

Antidepressant pharmaceuticals in aquatic systems, individual-level ecotoxicological effects: growth, survival and behavior.

The goal of this work was to compare pO measured using both continuous wave (CW) and pulse electron paramagnetic resonance (EPR) spectroscopy. The Oxychip particle spin probe enabled longitudinal monitoring of pO in murine pancreatic tumor treated with gemcitabine during the course of therapy.

Pulse and CW EPR Oximetry Using Oxychip in Gemcitabine-Treated Murine Pancreatic Tumors.

Molecular oxygen, besides a photosensitizer and light of appropriate wavelength, is one of the three factors necessary for photodynamic therapy (PDT). In tumor tissue, PDT leads to the killing of tumor cells, destruction of endothelial cells and vasculature collapse, and the induction of strong immune responses. All these effects may influence the oxygenation levels, but it is the vasculature changes that have the main impact on pO. The purpose of our study was to monitor changes in tumor oxygenation after PDT and explore its significance for predicting long-term treatment response.

EPR Monitoring of Oxygenation Levels in Tumors After Chlorophyllide-Based Photodynamic Therapy May Allow for Early Prediction of Treatment Outcome.

Aclarubicin (aclacinomycin A) is one of the anthracycline antineoplastic antibiotics with a multifaceted mechanism of antitumor activity. As a second-generation drug, it offers several advantages compared to standard anthracycline drugs such as doxorubicin or daunorubicin, which could position it as a potential blockbuster drug in antitumor therapy. Key mechanisms of action for aclarubicin include the inhibition of both types of topoisomerases, suppression of tumor invasion processes, generation of reactive oxygen species, inhibition of chymotrypsin-like activity, influence on cisplatin degradation, and inhibition of angiogenesis. Therefore, aclarubicin appears to be an ideal candidate for antitumor therapy. However, despite initial interest in its clinical applications, only a limited number of high-quality trials have been conducted thus far. Aclarubicin has primarily been evaluated as an induction therapy in acute myeloid and lymphoblastic leukemia. Studies have indicated that aclarubicin may hold significant promise for combination therapies with other anticancer drugs, although further research is needed to confirm its potential. This paper provides an in-depth exploration of aclarubicin's diverse mechanisms of action, its pharmacokinetics, potential toxicity, and the clinical trials in which it has been investigated.

Aclarubicin: contemporary insights into its mechanism of action, toxicity, pharmacokinetics, and clinical standing.

An increasing number of drugs introduced to the market and numerous repositories of compounds with confirmed activity have posed the need to revalidate the state-of-the-art rules that determine the ranges of properties the compounds should possess to become future drugs. In this study, we designed a series of two chemotypes of aryl-piperazine hydantoin ligands of 5-HTR, an attractive target in search for innovative CNS drugs, with higher molecular weight (close to or over 500). Consequently, 14 new compounds were synthesised and screened for their receptor activity accompanied by extensive docking studies to evaluate the observed structure-activity/properties relationships. The ADMET characterisation in terms of the biological membrane permeability, metabolic stability, hepatotoxicity, cardiotoxicity, and protein plasma binding of the obtained compounds was carried out in vitro. The outcome of these studies constituted the basis for the comprehensive challenge of computational tools for ADMET properties prediction. All the compounds possessed high affinity to the 5-HTR (K below 250 nM for all analysed structures) with good selectivity over 5-HTR and varying affinity towards 5-HTR, 5-HTR and DR. For the best compounds of this study, the expression profile of genes associated with neurodegeneration, anti-oxidant response and anti-inflammatory function was determined, and the survival of the cells (SH-SY5Y as an in vitro model of Alzheimer's disease) was evaluated. One 5-HTR agent (32) was characterised by a very promising ADMET profile, i.e. good membrane permeability, low hepatotoxicity and cardiotoxicity, and high metabolic stability with the simultaneous high rate of plasma protein binding and high selectivity over other GPCRs considered, together with satisfying gene expression profile modulations and neural cell survival. Such encouraging properties make it a good candidate for further testing and optimisation as a potential agent in the treatment of CNS-related disorders.

Article	Year
Photodynamic Therapy and Hyperthermia in Combination Treatment-Neglected Forces in the Fight against Cancer. Pharmaceutics\| PubMed ID: 34452108	2021
Antidepressant pharmaceuticals in aquatic systems, individual-level ecotoxicological effects: growth, survival and behavior. Aquatic toxicology (Amsterdam, Netherlands)\| PubMed ID: 37167880	2023
Pulse and CW EPR Oximetry Using Oxychip in Gemcitabine-Treated Murine Pancreatic Tumors. Molecular imaging and biology\| PubMed ID: 37784004	2024
EPR Monitoring of Oxygenation Levels in Tumors After Chlorophyllide-Based Photodynamic Therapy May Allow for Early Prediction of Treatment Outcome. Molecular imaging and biology\| PubMed ID: 38296885	2024
Aclarubicin: contemporary insights into its mechanism of action, toxicity, pharmacokinetics, and clinical standing. Cancer chemotherapy and pharmacology\| PubMed ID: 38965080	2024
Unlocking the potential of higher-molecular-weight 5-HTR ligands: Synthesis, affinity, and ADMET examination. Bioorganic chemistry\| PubMed ID: 39079393	2024

Aleksandra Murzyn

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