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1.
Invest New Drugs ; 40(1): 30-41, 2022 02.
Article in English | MEDLINE | ID: mdl-34478029

ABSTRACT

Breast cancer is the leading cause of cancer death among women worldwide. For this reason, the development of new therapies is still essential. In this work we have analyzed the antitumor potential of levoglucosenone, a chiral building block derived from the pyrolysis of cellulose-containing materials such as soybean hulls, and three structurally related analogues. Employing human and murine mammary cancer models, we have evaluated the effect of our compounds on cell viability through MTS assay, apoptosis induction by acridine orange/ethidium bromide staining and/or flow cytometry and the loss of mitochondrial potential by tetramethylrhodamine methyl ester staining. Autophagy and senescence induction were also evaluated by Western blot and ß-galactosidase activity respectively. Secreted metalloproteases activity was determined by quantitative zymography. Migratory capacity was assessed by wound healing assays while invasive potential was analyzed using Matrigel-coated transwell chambers. In vivo studies were also performed to evaluate subcutaneous tumor growth and experimental lung colonization. All compounds impaired in vitro proliferation with IC50 values in a range of low micromolar. Apoptosis was identified as the main mechanism responsible for the reduction of monolayer cell content induced by the compounds without detecting modulations of autophagy or senescence processes. Two of the four compounds (levoglucosenone and its brominated variant) were able to modulate in vitro events associated with tumor progression, such as migratory potential, invasiveness, and proteases secretion. Furthermore, tumor volume and metastatic spread were significantly reduced in vivo after the treatment these two compounds. Here, we could obtain from soybean hulls, a material with almost no commercial value, a variety of chemical compounds useful for breast cancer treatment.


Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Breast Neoplasms/pathology , Bridged Bicyclo Compounds, Heterocyclic/pharmacology , Glucose/analogs & derivatives , Animals , Antineoplastic Agents, Phytogenic/chemistry , Apoptosis/drug effects , Bridged Bicyclo Compounds, Heterocyclic/chemistry , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/drug effects , Cellulose/chemistry , Dose-Response Relationship, Drug , Glucose/chemistry , Glucose/pharmacology , Humans , Inhibitory Concentration 50 , Mice , Mice, Inbred BALB C , Tumor Burden/drug effects
3.
Toxicology ; 463: 152967, 2021 11.
Article in English | MEDLINE | ID: mdl-34619302

ABSTRACT

Blister agents damage the skin, eyes, mucous membranes and subcutaneous tissues. Other toxic effects may occur after absorption. The response of the Scientific Advisory Board (SAB) of the Organisation for the Prohibition of Chemical Weapons (OPCW) to a request from the OPCW Director-General in 2013 on the status of medical countermeasures and treatments to blister agents is updated through the incorporation of the latest information. The physical and toxicological properties of sulfur mustard and clinical effects and treatments are summarised. The information should assist medics and emergency responders who may be unfamiliar with the toxidrome of sulfur mustard and its treatment.


Subject(s)
Chemical Warfare Agents/poisoning , Mustard Gas/poisoning , Animals , Humans , Medical Countermeasures
4.
Toxicology ; 415: 56-69, 2019 03 01.
Article in English | MEDLINE | ID: mdl-30639304

ABSTRACT

The Scientific Advisory Board (SAB) of the Organisation for the Prohibition of Chemical Weapons (OPCW) has provided advice on assistance and protection in relation to the Chemical Weapons Convention. In this, the first of several papers describing the SAB's work on this topic, we describe advice given in response to questions from the OPCW Director-General in 2013 and 2014 on the status of available medical countermeasures and treatments to organophosphorus nerve agents. This paper provides the evidence base for this advice which recommended to the OPCW pretreatments, emergency care, and long-term treatments that were available at the time of the request for this class of chemical warfare agent (CWA). It includes a bibliography of over 140 scientific references, which can be used as a platform for watching future medical countermeasure developments. The information provided in this paper should serve as a valuable reference for medical professionals and emergency responders who may have no knowledge of the symptoms and treatment options of exposure to nerve agents.


Subject(s)
Advisory Committees , Chemical Warfare Agents/poisoning , Medical Countermeasures , Nerve Agents/poisoning , Humans , Poisoning/therapy
5.
Toxicology ; 413: 13-23, 2019 02 01.
Article in English | MEDLINE | ID: mdl-30500381

ABSTRACT

The Scientific Advisory Board (SAB) of the Organisation for the Prohibition of Chemical Weapons (OPCW) has provided advice in relation to the Chemical Weapons Convention on assistance and protection. We present the SAB's response to a request from the OPCW Director-General in 2014 for information on the best practices for preventing and treating the health effects from acute, prolonged, and repeated organophosphorus nerve agent (NA) exposure. The report summarises pre- and post-exposure treatments, and developments in decontaminants and adsorbing materials, that at the time of the advice, were available for NAs. The updated information provided could assist medics and emergency responders unfamiliar with treatment and decontamination options related to exposure to NAs. The SAB recommended that developments in research on medical countermeasures and decontaminants for NAs should be monitored by the OPCW, and used in assistance and protection training courses and workshops organised through its capacity building programmes.


Subject(s)
Advisory Committees/standards , Chemical Warfare Agents/toxicity , Decontamination/standards , Medical Countermeasures , Nerve Agents/toxicity , Antidotes/therapeutic use , Decontamination/methods , Humans , Netherlands , Organophosphorus Compounds/toxicity , Treatment Outcome
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