Reshetov I.V., Romanko Yu.S. Fundamental and applied research of the Institute of Cluster Oncology named after L.L. Levshin on the development of methods for the treatment of diseases of the head and neck. Head and neck. Russian Journal. 2023;11(2):81–91 The authors are responsible for the originality of the data presented and the possibility of publishing illustrative material – tables, drawings, photographs of patients.
Institute of Cluster Oncology named after L.L. Levshin of the First Moscow State Medical University (Institute) is the assignee of the first oncological Institute in Europe – Institute named after Morozov for the Treatment of Tumors of the Imperial Moscow University. Currently, the Institute is a university experimental — clinical cluster, which conducts multilateral research in the field of biology and medicine.
The publication is an overview of the main results of the Institute as part of the implementation of work on the state assignment in 2020–2021. In the field of experimental and clinical development of new methods for the treatment of various diseases of the head and neck.
So, within the state task, a study was conducted that demonstrated the high efficiency of replacing jaw defects using 3D printing and the feasibility of further clinical research in this direction.
A study was made of cancer biomarkers derived from the tumor tissue microenvironment (TME), with particular attention to the extracellular matrix (ECM) and its products of activity and degradation. ECM-associated extracellular vesicles, ECM biomechanical characteristics, and ECM-derived biomarkers predictive of response to immunotherapy were studied. ECM has been shown to be a critical factor in malignant tumors. It is recommended that ECM-derived biomarkers be included in diagnostic and prognostic marker panels in the clinic.
It is shown that the use of modern systems of THz spectroscopy and visualization opens up new possibilities in the label-free diagnosis of tumors, the treatment of cancer and inflammatory diseases. Models have been developed to fully describe the interaction of a THz wave with human brain tissues within the framework of classical electrodynamics, which is important for future research in the field of THz tumor neurodiagnosis. The need for a systematic study of various modes of THz irradiation of tissues and cells, including continuous and pulsed radiation, different powers, number and duration of exposure cycles, is emphasized.
Liposomes containing MANα1-2MAN-PEG-DOPE were first tested as a nanocarrier DNA vaccine in cattle as a prophylactic against bovine herpes-1 (BoHV-1) infection. The proposed method increases immunogenicity and leads to long-term immunity.
A dendritic cell (DC) targeting strategy has been proposed that uses a specific receptor known as DC-SIGN with its ability to bind α1,2-mannobiase, which is present at the ends of oligosaccharides in some viruses, bacteria and other pathogens.
The Digital Display Precision Predictor (DDPP) algorithm is presented, aimed at identifying transcriptomic predictors of treatment outcome. Transcriptomic analysis, based on comparisons between tumor and normal tissue, compared with genomic analysis alone increased the number of patients eligible for targeted therapy by about a third.
Work has been carried out to study the activation of neutrophils as an important therapeutic target in the treatment of cancer, and the use of neutrophils or neutrophil membrane vesicles as drug delivery and targeting vehicles.
It has been shown that lipid-based nanocarriers can open up many opportunities to overcome the limitations of cell therapy and be used to deliver appropriate growth factors to the site of tissue damage and create conditions conducive to cell regeneration.
Delivery of therapeutic agents to brain tissue is one of the most important problems in medicine. The use of transferrin, a protein, is promising for activating the surface of nanoparticles in order to direct them to the brain.
An analysis was made of the use of polymer micelles in the targeted delivery of anticancer drugs, gene therapy, and diagnostic agents.
The advantages of dendrimers, a unique drug delivery system, are analyzed: efficient loading of therapeutic and imaging materials, desired delivery, universal choice of the route of administration, monodisperse system, improved pharmacokinetic and pharmacodynamic profiling.
Lipid nanoparticles, dynamic polyconjugates, GalNAc-siRNA conjugates, exosomes, and erythrocyte systems have been reviewed, demonstrating efficient siRNA delivery to cancer cells.
The combination of salinomycin and paclitaxel delivered by a liposomal preparation modified with mAb 2C5 has been demonstrated to have high antitumor efficacy.
The effectiveness of cell-penetrating peptides (CPPs) in delivering drugs and genes (siRNA, pDNA) to tumor sites to combat drug resistance was analyzed.
An experimental study was made of the effectiveness of direct electrical stimulation of the posterior cricoarytenoid muscle for controlled opening of the glottis. Neurostimulation has a great potential for stimulating the human larynx. The efficiency of transplantation of parietal cells obtained from the olfactory lining of the nose of rats and humans on changing the size of post-traumatic spinal cord cysts has been established.
The pathways and profiles of DNA expression in uveal melanoma have been determined, which will contribute to the creation of prognostic models that can lead to an improvement in the prognosis for patients with this disease. The effectiveness of cell-penetrating peptides (CPPs) in delivering drugs and genes (siRNA, pDNA) to tumor sites to combat drug resistance was analyzed.
An experimental study was made of the effectiveness of direct electrical stimulation of the posterior cricoarytenoid muscle for controlled opening of the glottis. Neurostimulation has a great potential for stimulating the human larynx. The transplantation of ensheathing cells obtained from the olfactory lining of the nose of rats and humans was found to be effective in changing the size of post-traumatic spinal cord cysts.
The pathways and profiles of DNA expression in uveal melanoma have been determined, which will contribute to the creation of prognostic models that can lead to an improvement in the prognosis for patients with this disease. The accumulation of methylene blue both in various tissues and in immune cells has been established, which indicates a potential correction of the immune response in patients with COVID-19 and a change in the macrophage phenotype, which can be achieved by deactivating inflammatory macrophages in tissues using red laser radiation. When modeling septoplasty, a change in heart rate variability, an increase in the concentration of corticosterone in the blood plasma in rats was established. As a result of a comparative analysis of the effect of septoplasty and modeling of sinus lift in rats on changes in the frequency domain of heart rate variability were established an increase in the activity of the sympathetic nervous system and a shift in metabolism under the influence of postoperative inflammation.
Based on the studies, it was found that photobiomodulation therapy after septoplasty shows better results compared to the standard rehabilitation of patients after septoplasty: it helps to reduce the severity of pain and inflammatory response to surgical stress and leads to less pronounced changes in the autonomic nervous system in response to surgical stress.
A separate staging system for oropharyngeal cancer associated with human papillomavirus is considered.
The advantages of three-dimensional (3D) surface scanning over ultrasound during preoperative planning are shown, especially in «difficult» areas of the face.
Data were obtained on the three-dimensional course of the angular artery within the nasolabial sulcus depending on age, sex and body mass index. With age, the depth and lateral distance between the arteries and sulci decreases significantly, and therefore there is no guaranteed safe place in the midface for minimally invasive procedures. The results of the study will help improve safety in minimally invasive treatments.
Provided objective evidence of antagonistic skin movement between the medial and lateral midface. The functional border, identified by the 3D image, corresponds to the anatomical location of the ligament line.
When studying the relationship of forehead fascial anatomy with the effectiveness of treatment with neuromodulators, it was found that the deep injection technique leads to a better result.
The effectiveness of laser-induced fluorescent diagnostics and photodynamic therapy with sublingual administration of 5-ALA to patients in the treatment of precancerous lesions of the oral cavity and larynx has been demonstrated. Key words: 3D printing of a jaw implant, cancer biomarkers, THz irradiation of tissues and cells, vaccine, DC- SIGN, neutrophil activation, cell therapy, lipid-based nanocarriers, liposomes, transferrin, polymer micelles, nanopreparations, peptides, neurostimulation, parietal cell transplantation, DNA expression pathways and profiles, uveal melanoma, methylene blue, COVID-19, laser radiation, heart rate variability, photobiomodulation therapy, septoplasty, thyroidectomy, oropharyngeal cancer, HPV, 3D surface scanning, facial artery, fluorescent diagnostics, photodynamic therapy, 5-ALA
Conflicts of interest. The authors have no conflicts of interest to declare.
Funding. There was no funding for this study