1,721,162 research outputs found
Women’s Special Issue Series: Biomedicines
Full text linkFollowing the invitation of Biomedicines, we decided to accept the project of this Special Issue because we believe that in many situations gender prejudices still exist and put women in a disadvantaged position for the dissemination of their research, preventing the scientific community from benefiting from a plurality of voices in the interpretation of scientific research. The aim of our Special Issue, entitled “Women’s Special Issue Series: Biomedicines” was to celebrate and highlight the achievements of women in the development of new molecules and therapies, particularly regarding new therapeutic targets, therapeutic strategies, and research on biomedicines and biopharmaceutical products. This Special Issue includes nine manuscripts, among which there are seven high-quality research articles, one meta-analysis and systematic review, and one comprehensive review article, published from 2022 to 2023
Bouganin, an attractive weapon for immunotoxins
Full text linkBougainvillea (Bougainvillea spectabilis Willd.) is a plant widely used in folk medicine and many extracts from different tissues of this plant have been employed against several pathologies. The observation that leaf extracts of Bougainvillea possess antiviral properties led to the purification and characterization of a protein, named bouganin, which exhibits typical characteristics of type 1 ribosome-inactivating proteins (RIPs). Beyond that, bouganin has some peculiarities, such as a higher activity on DNA with respect to ribosomal RNA, low systemic toxicity, and immunological properties quite different than other RIPs. The sequencing of bouganin and the knowledge of its three-dimensional structure allowed to obtain a not immunogenic mutant of bouganin. These features make bouganin a very attractive tool as a component of immunotoxins (ITs), chimeric proteins obtained by linking a toxin to a carrier molecule. Bouganin-containing ITs showed very promising results in the experimental treatment of both hematological and solid tumors, and one bouganin-containing IT has entered Phase I clinical trial. In this review, we summarize the milestones of the research on bouganin such as bouganin chemico-physical characteristics, the structural properties and de-immunization studies. In addition, the in vitro and in vivo results obtained with bouganin-containing ITs are summarized
Novel Strategies to Improve Rituximab Efficacy in Non-Hodgkin's Lymphomas
Full text linkNon-Hodgkin’s lymphomas (NHLs) are the second fastest growing cancer in terms of incidence and deaths in the United States and Europe. NHLs are a heterogeneous cancer group including several haematological neoplasias with different degree of aggressiveness. In spite of the progresses, conventional therapies do not ensure long-term survival [1]. The NHL patients, who have a poor life expectation, could take advantage from innovative therapeutic strategies, such as immunotherapy. Specific antibodies can preferentially bind tumour cells over normal tissues. This specificity is based upon characteristics (surface antigens) that are completely independent from the parameters that allow for differential toxicity of chemo- and radiotherapy. The vascular nature of most lymphomas and their antigen expression make these tumours a favourable setting for treatment with monoclonal antibodies. In fact, the first successful use of antibodies as treatments for cancer was demonstrated in NHLs [2,3]. CD20 has been largely exploited as target antigen for immunotherapy with antibodies because it is expressed at high levels on B-lymphoma cells and is not expressed on stem cells [4].</p
Xanthine Oxidoreductase in Drug Metabolism: Beyond A Role as a Detoxifying Enzyme
No full textThe enzyme xanthine oxidoreductase (XOR) catalyzes the last two steps of purine catabolism in the highest uricotelic primates. XOR is an enzyme with dehydrogenase activity that, in mammals, may be converted into oxidase activity under a variety of pathophysiologic conditions. XOR activity is highly regulated at the transcriptional and post-translational levels and may generate reactive oxygen and nitrogen species, which trigger different consequences, ranging from cytotoxicity to inflammation. The low specificity for substrates allows XOR to metabolize a number of endogenous metabolites and a variety of exogenous compounds, including drugs. The present review focuses on the role of XOR as a drug-metabolizing enzyme, specifically for drugs with anticancer, antimicrobial, antiviral, immunosuppressive or vasodilator activities, as well as drugs acting on metabolism or inducing XOR expression. XOR has an activating role that is essential to the pharmacological action of quinone drugs, cyadox, antiviral nucleoside analogues, allopurinol, nitrate and nitrite. XOR activity has a degradation function toward thiopurine nucleotides, pyrazinoic acid, methylxanthines and tolbutamide, whose half-life may be prolonged by the use of XOR inhibitors. In conclusion,: to avoid potential drug interaction risks, such as a toxic excess of drug bioavailability or a loss of drug efficacy, caution is suggested in the use of XOR inhibitors, as in the case of hyperuricemic patients affected by gout or tumor lysis syndrome, when it is necessary to simultaneously administer therapeutic substances that are activated or degraded by the drug-metabolizing activity of XOR
Toxic Plant Proteins as Experimental Drugs for Human Pathologies
Full text linkEditorial on the Research Topic
Toxic Plant Proteins as Experimental Drugs for Human Pathologies
Front. Pharmacol., 28 April 2021 | https://doi.org/10.3389/fphar.2021.68992
Plant Toxin-Based Immunotoxins for Cancer Therapy: A Short Overview
Full text linkImmunotoxins are chimeric proteins obtained by linking a toxin to either an intact antibody or an antibody fragment. Conjugation can be obtained by chemical or genetic engineering, where the latter yields recombinant conjugates. An essential requirement is that the target molecule recognized by the antibody is confined to the cell population to be deleted, or at least that it is not present on stem cells or other cell types essential for the organism’s survival. Hundreds of different studies have demonstrated the potential for applying immunotoxins to many models in pre-clinical studies and in clinical trials. Immunotoxins can be theoretically used to eliminate any unwanted cell responsible for a pathological condition. The best results have been obtained in cancer therapy, especially in hematological malignancies. Among plant toxins, the most frequently employed to generate immunotoxins are ribosome-inactivating proteins, the most common being ricin. This review summarizes the various approaches and results obtained in the last four decades by researchers in the field of plant toxin-based immunotoxins for cancer therapy
Heterophyllin: A New Adenia Toxic Lectin with Peculiar Biological Properties
Full text linkRibosome-inactivating proteins (RIPs) are plant toxins that were identified for their ability to irreversibly damage ribosomes, thereby causing arrest of protein synthesis and induction of cell death. The RIPs purified from Adenia plants are the most potent ones. Here, we describe a novel toxic lectin from Adenia heterophylla caudex, which has been named heterophyllin. Heterophyllin shows the enzymatic and lectin properties of type 2 RIPs. Interestingly, in immunoreactivity experiments, heterophyllin poorly cross-reacts with sera against all other tested RIPs. The cytotoxic effects and death pathways triggered by heterophyllin were investigated in three human-derived cell lines: NB100, T24, and MCF7, and compared to ricin, the most known and studied type 2 RIP. Heterophyllin was able to completely abolish cell viability at nM concentration. A strong induction of apoptosis, but not necrosis, and the involvement of oxidative stress and necroptosis were observed in all the tested cell lines. Therefore, the enzymatic, immunological, and biological activities of heterophyllin make it an interesting molecule, worthy of further in-depth analysis to verify its possible pharmacological application
High in Vitro Anti-Tumor Efficacy of Dimeric Rituximab/Saporin-S6 Immunotoxin
Full text linkThe anti-CD20 mAb Rituximab has revolutionized lymphoma therapy, in spite of a number of unresponsive or relapsing patients. Immunotoxins, consisting of toxins coupled to antibodies, are being investigated for their potential ability to augment Rituximab efficacy. Here, we compare the anti-tumor effect of high- and low-molecular-weight Rituximab/saporin-S6 immunotoxins, named HMW-IT and LMW-IT, respectively. Saporin-S6 is a potent and stable plant enzyme belonging to ribosome-inactivating proteins that causes protein synthesis arrest and consequent cell death. Saporin-S6 was conjugated to Rituximab through an artificial disulfide bond. The inhibitory activity of HMW-IT and LMW-IT was evaluated on cell-free protein synthesis and in two CD20+ lymphoma cell lines, Raji and D430B. Two different conjugates were separated on the basis of their molecular weight and further characterized. Both HMW-IT (dimeric) and LMW-IT (monomeric) maintained a high level of enzymatic activity in a cell-free system. HMW-IT, thanks to a higher toxin payload and more efficient antigen capping, showed stronger in vitro anti-tumor efficacy than LMW-IT against lymphoma cells. Dimeric HMW-IT can be used for lymphoma therapy at least for ex vivo treatments. The possibility of using HMW-IT augments the yield in immunotoxin preparation and allows the targeting of antigens with low internalization rates
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