Milos Arsenijevic

Bio: Milos Arsenijevic is an academic researcher from University of Kragujevac. The author has contributed to research in topics: Cytotoxicity & Substitution reaction. The author has an hindex of 4, co-authored 10 publications receiving 80 citations.

Cytotoxicity of gold(III) Complexes on A549 Human Lung Carcinoma Epithelial Cell Line

Abstract: We have studied the kinetics of the complex formation of gold(III) complexes, [Au(en)Cl2]+ (dichlorido( ethylendiamine)aurate(III)-ion) [Au(dach)Cl2] (dichloride(1,2-diaminocyclohexane)aurate(III)-ion) and [Au(bipy)Cl2]+ (dichlorido(2,2-bipyridyl)aurate(III)-ion) with guanosine5-monophosphate (5-GMP). It was shown that 5-GMP have a high affinity for gold(III) complex, which may have important biological implications, since the interactions of Au(III) with DNA are thought to be responsible for the anti-tumor activity. The [Au(bipy)Cl2]+ complex is more reactive than [Au(en)Cl2]+ or [Au(dach)Cl2]+. The activation parameters for all studied reactions suggest an associative substitution mechanism. The cytotoxicity of gold(III) complexes was tested on A549 human lung carcinoma epithelial cell line and was evaluated by cytotoxic (MTT and LDH test) and apoptotic assays. The results showed that all tested gold(III) complexes displayed cytotoxic effect on A549 cells. Among the tested gold (III) complexes, AuBIPY showed the best cytotoxic effects.

Cytotoxic properties of platinum(IV) and dinuclear platinum(II) complexes and their ligand substitution reactions with guanosine-5′-monophosphate

Abstract: The substitution reaction of the Pt(IV) complex [PtCl4(bipy)] with guanosine-5′-monophosphate (5′-GMP) was studied by UV–Vis spectrophotometry. This reaction was investigated under pseudo-first-order conditions at 37 °C in 25 mM Hepes buffer (pH = 7.2) in the presence of 10 mM NaCl to prevent the hydrolysis of the complex. The substitution of chlorides in [{trans-Pt(NH3)2Cl}2(μ-1,2-bis(4-pyridyl)ethane)](ClO4)2 (Pt3) complex by 5′-GMP was followed by 1H NMR spectroscopy under second-order conditions. Very similar values for the rate constants of both substitution steps were obtained. The Pt(IV) complexes, [PtCl4(bipy)] and [PtCl4(dach)], as well as dinuclaer Pt(II) [{trans-Pt(NH3)2Cl}2(μ-pyrazine)](ClO4)2 (Pt1), [{trans-Pt(NH3)2Cl}2(μ-4,4′-bipyridyl)](ClO4)2 · DMF (Pt2) and [{trans-Pt(NH3)2Cl}2(μ-1,2-bis(4-pyridyl)ethane)](ClO4)2 (Pt3) complexes, displayed potent cytotoxic activity against human ovarium carcinoma cell line TOV21G and lower activity toward human colon carcinoma HCT116 cell line at the same concentrations. Our data indicate that these platinum complexes could be explored further, as potential therapeutic agents for ovarian cancer.

In vitro and in vivo anti-tumor effects of selected platinum(IV) and dinuclear platinum(II) complexes against lung cancer cells

Abstract: In the present study, cytotoxic effects of cisplatin, the most usually used chemotherapeutic agent, were compared with new designed platinum(IV) ([PtCl4(en)] (en = ethylenediamine) and [PtCl4(dach)]) (dach = (±)-trans-1,2-diaminocyclohexane) and platinum(II) complexes ([{trans-Pt(NH3)2Cl}2(μ-pyrazine)](ClO4)2 (Pt1), [{trans-Pt(NH3)2Cl}2(μ-4,4'-bipyridyl)](ClO4)2DMF(Pt2),[{trans-Pt(NH3)2Cl}2(μ-1,2-bis(4pyridyl)ethane)](ClO4)2 (Pt3)), in vitro and in vivo against human and murine lung cancer cells, to determine anti-tumor potential of newly synthesized platinum-based drugs in the therapy of lung cancer. Results obtained by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide], Lactate dehydrogenase and Annexin V/Propidium Iodide assays showed that, among all tested complexes, [PtCl4(en)] had the highest cytotoxicity against human and murine lung carcinoma cells in vitro. [PtCl4(en)] showed significantly higher cytotoxicity then cisplatin in all tested concentrations, mainly by inducing apoptosis in lung cancer cells. [PtCl4(en)] was well tolerated in vivo. Clinical signs of [PtCl4(en)]-induced toxicity, such as changes in food, water consumption or body weight, nephrotoxicity or hepatotoxicity was not observed in [PtCl4(en)]-treated mice. [PtCl4(en)] managed to increase presence of CD45+ leukocytes, including F4/80+ macrophages, CD11c+ dendritic cells, CD4+ helper and CD8+ cytotoxic T cells (CTLs) in the lungs, cytotoxic NK, NKT and CTLs in the spleens of tumor bearing mice, resulting with reduction of metastatic lesions in the lungs, indicating its potential to stimulate anti-tumor immune response in vivo. Due to its anti-tumor cytotoxicity, biocompatibility, and potential for stimulation of anti-tumor immune response, [PtCl4(en)] may be a good candidate for further testing in the field of medicinal chemistry.

Automatic Evaluation of the Lung Condition of COVID-19 Patients Using X-ray Images and Convolutional Neural Networks.

Abstract: COVID-19 represents one of the greatest challenges in modern history. Its impact is most noticeable in the health care system, mostly due to the accelerated and increased influx of patients with a more severe clinical picture. These facts are increasing the pressure on health systems. For this reason, the aim is to automate the process of diagnosis and treatment. The research presented in this article conducted an examination of the possibility of classifying the clinical picture of a patient using X-ray images and convolutional neural networks. The research was conducted on the dataset of 185 images that consists of four classes. Due to a lower amount of images, a data augmentation procedure was performed. In order to define the CNN architecture with highest classification performances, multiple CNNs were designed. Results show that the best classification performances can be achieved if ResNet152 is used. This CNN has achieved AUCmacro¯ and AUCmicro¯ up to 0.94, suggesting the possibility of applying CNN to the classification of the clinical picture of COVID-19 patients using an X-ray image of the lungs. When higher layers are frozen during the training procedure, higher AUCmacro¯ and AUCmicro¯ values are achieved. If ResNet152 is utilized, AUCmacro¯ and AUCmicro¯ values up to 0.96 are achieved if all layers except the last 12 are frozen during the training procedure.

Sternum Resection and Chest Wall Reconstruction with Metaacrilate Implant in Tuberculosis

Abstract: We report a case of successful sternum and ribs/cartilage resection and chest wall reconstruction with a methacrylate implant produced using a three-dimensional model in a patient with a tuberculotic mass in this region. Clinical and radiologic follow-up 2 years after surgery showed excellent cosmetic and functional outcome.

Antitumour metal compounds: more than theme and variations

Abstract: Triggered by the resounding success of cisplatin, the past decades have seen tremendous efforts to produce clinically beneficial analogues. The recent achievement of oxaliplatin for the treatment of colon cancer should, however, not belie the imbalance between a plethora of investigated complexes and a very small number of clinically approved platinum drugs. Strategies opening up new avenues are increasingly being sought using complexes of metals other than platinum such as ruthenium or gallium. Based on the chemical differences between these metals, the spectrum of molecular mechanisms of action and potential indications can be broadened substantially. Other approaches focus on complexes with tumour-targeting properties, thereby maximizing the impact on cancer cells and minimizing the problem of adverse side effects, and complexes with biologically active ligands.

Metal complexes in cancer therapy - an update from drug design perspective.

Abstract: In the past, metal-based compounds were widely used in the treatment of disease conditions, but the lack of clear distinction between the therapeutic and toxic doses was a major challenge. With the discovery of cisplatin by Barnett Rosenberg in 1960, a milestone in the history of metal-based compounds used in the treatment of cancers was witnessed. This forms the foundation for the modern era of the metal-based anticancer drugs. Platinum drugs, such as cisplatin, carboplatin and oxaliplatin, are the mainstay of the metal-based compounds in the treatment of cancer, but the delay in the therapeutic accomplishment of other metal-based compounds hampered the progress of research in this field. Recently, however, there has been an upsurge of activities relying on the structural information, aimed at improving and developing other forms of metal-based compounds and nonclassical platinum complexes whose mechanism of action is distinct from known drugs such as cisplatin. In line with this, many more metal-based compounds have been synthesized by redesigning the existing chemical structure through ligand substitution or building the entire new compound with enhanced safety and cytotoxic profile. However, because of increased emphasis on the clinical relevance of metal-based complexes, a few of these drugs are currently on clinical trial and many more are awaiting ethical approval to join the trial. In this review, we seek to give an overview of previous reviews on the cytotoxic effect of metal-based complexes while focusing more on newly designed metal-based complexes and their cytotoxic effect on the cancer cell lines, as well as on new approach to metal-based drug design and molecular target in cancer therapy. We are optimistic that the concept of selective targeting remains the hope of the future in developing therapeutics that would selectively target cancer cells and leave healthy cells unharmed.

Metal Drugs and the Anticancer Immune Response.

Abstract: The immune system deploys a multitude of innate and adaptive mechanisms not only to ward off pathogens but also to prevent malignant transformation ("immune surveillance"). Hence, a clinically apparent tumor already reflects selection for those malignant cell clones capable of evading immune recognition ("immune evasion"). Metal drugs, besides their well-investigated cytotoxic anticancer effects, massively interact with the cancer-immune interface and can reverse important aspects of immune evasion. This topic has recently gained intense attention based on combination approaches with anticancer immunotherapy (e.g., immune checkpoint inhibitors), a strategy recently delivering first exciting results in clinical settings. This review summarizes the promising but still extremely fragmentary knowledge on the interplay of metal drugs with the fidelity of anticancer immune responses but also their role in adverse effects. It highlights that, at least in some cases, metal drugs can induce long-lasting anticancer immune responses. Important steps in this process comprise altered visibility and susceptibility of cancer cells toward innate and adaptive immunity, as well as direct impacts on immune cell populations and the tumor microenvironment. On the basis of the gathered information, we suggest initiating joint multidisciplinary programs to implement comprehensive immune analyses into strategies to develop novel and smart anticancer metal compounds.

Applications of artificial intelligence in COVID-19 pandemic: A comprehensive review

Abstract: During the current global public health emergency caused by novel coronavirus disease 19 (COVID-19), researchers and medical experts started working day and night to search for new technologies to mitigate the COVID-19 pandemic. Recent studies have shown that artificial intelligence (AI) has been successfully employed in the health sector for various healthcare procedures. This study comprehensively reviewed the research and development on state-of-the-art applications of artificial intelligence for combating the COVID-19 pandemic. In the process of literature retrieval, the relevant literature from citation databases including ScienceDirect, Google Scholar, and Preprints from arXiv, medRxiv, and bioRxiv was selected. Recent advances in the field of AI-based technologies are critically reviewed and summarized. Various challenges associated with the use of these technologies are highlighted and based on updated studies and critical analysis, research gaps and future recommendations are identified and discussed. The comparison between various machine learning (ML) and deep learning (DL) methods, the dominant AI-based technique, mostly used ML and DL methods for COVID-19 detection, diagnosis, screening, classification, drug repurposing, prediction, and forecasting, and insights about where the current research is heading are highlighted. Recent research and development in the field of artificial intelligence has greatly improved the COVID-19 screening, diagnostics, and prediction and results in better scale-up, timely response, most reliable, and efficient outcomes, and sometimes outperforms humans in certain healthcare tasks. This review article will help researchers, healthcare institutes and organizations, government officials, and policymakers with new insights into how AI can control the COVID-19 pandemic and drive more research and studies for mitigating the COVID-19 outbreak.

Gold(III) complexes in medicinal chemistry

Abstract: A number of gold(III) compounds has been designed with the objective of overcoming the disadvantages associated with the platinum-based drugs for cancer treatment. Compounds of a remarkable structural manifold show significant antiproliferative effects in vitro against a number of cancer cells, including cisplatin resistant ones. The target of most of them is, unlike that of cisplatin, not the DNA. Although the mechanisms of action displayed by the gold compounds in biological media are still under investigation, many studies show evidence that the cellular targets are mitochondria-based. Recent advances in gold(III) medicinal chemistry also recommend such compounds for other pharmacological applications such as the treatment of viral or parasitic diseases. The radioactive isotopes (198)Au and (199)Au present potential in radiotherapy.