NEW POTENTIAL TREATMENT FOR BRAIN GLIOMA

Author(s):  
A.A. Gorbunov ◽  
T.M. Shipitsyna ◽  
E.B. Pilipenko-Koshel

According to the latest statistics, brain gliomas are the most common cause of death from CNS tumors. Brain gliomas are also ranked as the second (after stroke) cause of brain surgery The mortality rate from gliomas is high and sometimes reaches 80 %. It is because the tumor grows from undifferentiated cells, which causes its peracute development and malignant transformation. Symptoms of glioma occur at stages 3 and 4, when all treatment is symptomatic, and operations are palliative. In this regard, it is necessary to develop and introduce methods for non-surgical glioma treatment. These methods include the use of antisense oligonucleotides, optogenetics, and oncolytic viruses. The aim of antisense oligonucleotides is to replace a section in a glioma cell genome with a foreign one, which disrupts cell division and leads to apoptosis and necrosis of the entire tumor. Optogenetics excludes the introduction of substances into the body. It provides a certain light signal to glioma cells, which also suppresses the growth of an undifferentiated tumor. Oncolytic viruses are genetically modified viruses that identify tumor cells, penetrate into them and start a cascade of apoptotic reactions Despite all success, such methods are still studied at the laboratory level, their implementation in practical medicine is slow and cautious. However, insufficient knowledge retards the widespread use of potentially promising and effective drugs. Scientists around the world are developing methods to treat brain gliomas at different stages of their development. This article reflects modern achievements of scientists and neurosurgeons, describing new methods for brain glioma treatment. Key words: brain glioma, optogenetics, antisense oligonucleotides, oncolytic viruses, p53 gene. Согласно последним данным статистики, глиомы мозга являются наиболее частой причиной смертей от онкологии центральной нервной системы, а также занимают второе место по частоте как причина хирургических вмешательств на головной мозг, уступая инсультам. Смертность от глиом высока и порой достигает 80 %. Причина этого заключается в том, что опухоль растет из недифференцированных клеток, что обусловливает её молниеносный рост и быстрое озлокачествление. Симптомы глиомы возникают на 3–4 стадии развития, когда все лечение направлено на ликвидацию симптомов, а операции носят паллиативный характер. В связи с этим необходима разработка и внедрение методов по нехирургическому лечению глиом. Такими методами являются использование антисмысловых олигонуклеотидов, оптогенетика, применение онколитических вирусов. Суть использования антисмысловых олигонуклеотидов заключается в замене участка генома клетки глиомы на инородный, попавший извне, что нарушает деление клеток и приводит к апоптозу и некрозу всей опухоли. Оптогенетика исключает введение веществ в организм и заключается в подаче определенного светового сигнала на глиозные клетки, что также тормозит рост недифференцированной опухоли. Онколитические вирусы – это генномодифицированные вирусы, которые определяют опухолевые клетки, проникают в них и запускают каскад апоптотических реакций. Несмотря на все успехи, данные методы продолжают изучаться на уровне лабораторий, их внедрение в практическую медицину происходит медленно и со страхом. Однако недостаточная изученность тормозит широкое применение потенциально перспективных и эффективных лекарств. Учеными мира разрабатываются методы, позволяющие лечить глиомы мозга на разных стадиях их развития. Данная статья отображает современные достижения ученых и нейрохирургов в поисках возможности применения такого рода методов. Ключевые слова: глиома мозга, оптогенетика, антисмысловые олигонуклеотиды, онколитические вирусы, ген р53.

Author(s):  
G. V. Mokrov ◽  
T. D. Nikiforova ◽  
S. A. Kryzhanovskiy

The review discusses modern views about the structure and functions of Epac proteins (exchange proteins directly activated by cyclic adenosine monophosphate). The involvement of Epac proteins both in the regulation of the physiological functions of the body and in the initiation of various pathological processes allows to consider them as a fundamentally new biological target for creating original, highly effective drugs. Information on existing Epac protein agonists and antagonists was collected, and the influence of Epac ligands structure on the values of their affinity and selectivity was analyzed. Presumptive mechanisms of the interaction of ligands with Epac proteins are presented.


2020 ◽  
Vol 6 (1) ◽  
pp. 7-14
Author(s):  
I. S. Drachev ◽  
V. I. Legeza ◽  
A. B. Seleznev

The paper describes the current state of development of seasickness as one of movement disease variants. The given type of pathology occurs when combining different types of ship’s motion (rolling and pitching). Circular, vertical and slow movements induce more pronounced and frequent signs of seasickness than linear, horizontal and quick ones. In the view of majority of researchers, the most likely is an intersensory conflict theory i.e. violation of coherent functioning of afferent body systems performing spatial orientation, statokinetic equilibrium and keeping balance. The leading role is played by the functional dysfunction of the vestibular analyzer. The classification of means of preventing and stopping of motion sickness is given, the mechanisms of their action, specific activity and side effects are described. It has been shown that currently the most effective drugs are M-cholinergic antagonists (scopolamine hydrobromide) and H1-histamine antagonists of the 1st generation (dimenhydrinate, diphenhydramine, cyclizine, meclizine, promethazine, etc.). Of the antipsychotics and blockers of D2 receptors, prochlorperazine and metoclopramide are recommended. It is also worth to use prokinetics (domperidone, cisapride, renzapride, etc.), tranquilizers (barbiturates, benzodiazepines), sleeping pills and local anesthetics. Particular attention is paid to combination drugs, consisting of antiemetic and psychostimulating drugs, designed to maintain working capacity under the influence of seasickness factors on the body. Non-pharmacological means of preventing seasickness and alleviating its symptoms are described. The main directions of improving the system of measures aimed at maintaining efficiency in the presence of symptoms of seasickness are determined. 


Development ◽  
1982 ◽  
Vol 70 (1) ◽  
pp. 29-36
Author(s):  
V. Gremigni ◽  
M. Nigro ◽  
I. Puccinelli

The source and fate of blastema cells are important and still unresolved problems in planarian regeneration. In the present investigation we have attempted to obtain new evidence of cell dedifferentiation-redifferentiation by using a polyploid biotype of Dugesia lugubris s.1. This biotype is provided with a natural karyological marker which allows the discrimination of triploid embryonic and somatic cells from diploid male germ cells and from hexaploid female germ cells. Thanks to this cell mosaic we previously demonstrated that male germ cells take part in blastema formation and are then capable of redifferentiating into somatic cells. In the present investigation sexually mature specimens were transected behind the ovaries and the posterior stumps containing testes were allowed to regenerate the anterior portion of the body. Along with the usual hexaploid oocytes, a small percentage (3.2%) of tetraploid oocytes were produced from regenerated specimens provided with new ovaries. By contrast only hexaploid oocytes were produced from control untransected specimens. The tetraploid oocytes are interpreted as original diploid male germ cells which following the transection take part in blastema formation and then during regeneration redifferentiate into female germ cells thus doubling their chromosome number as usual for undifferentiated cells entering the female gonad in this biotype.


1930 ◽  
Vol 52 (3) ◽  
pp. 385-404 ◽  
Author(s):  
Claude E. Forkner

1. The theories for the origin of monocytes from myeloblasts, lymphocytes, endothelium, macrophages, and primitive cells are reviewed and considered. 2. Monocytes in all stages of development have been demonstrated to be present constantly in large numbers in all the lymph nodes of the body, except in the large mesenteric group. 3. The relations of these cells to undifferentiated cells, lymphocytes, macrophages, plasma cells, and endothelium are described. 4. The origin of adult monocytes from primitive undifferentiated cells through the stages of monoblasts and pre-monocytes is described and illustrated. 5. The demonstration in certain lymph nodes of innumerable monocytes in all stages of development permits of a shifting of the term "monoblast" from a more or less theoretical name to its proper place as a term designating that particular cell which is derived from a primitive undifferentiated cell and which is the immediate precursor of the pre-monocyte. 6. The term "pre-monocyte" is proposed to designate the intermediate stage between the monoblast and the mature monocyte. 7. Evidence is advanced to show that monocytes are an independent strain of cells, but that under physiological conditions they may be transformed into macrophages, this representing at least one way in which the latter cells normally are produced. 8. In no organs or tissues other than in certain specific lymph nodes, chiefly the peripheral group, can one constantly find monocytes in all stages of development. 9. Developing monocytes occasionally may be found in small numbers in the spleen, mesenteric lymph nodes, Peyer's patches, subcutaneous connective tissues, lungs, and omenta of normal rabbits, but their presence is by no means constant and their numbers are insignificant in comparison with those found in the peripheral lymph nodes. 10. Monocytes and pre-monocytes do not stain by the common methods used for the demonstration of the reticulo-endothelial system and therefore must be considered for the present as independent of this system, except in so far as monocytes may be transformed into macrophages. 11. Plasma cells, stained with the supravital technique, as seen in lymph nodes, are described. No basis has been found for the theory that plasma cells and monocytes are closely related structural elements.


1995 ◽  
Vol 10 (6) ◽  
pp. 442 ◽  
Author(s):  
Seung Hoon Lee ◽  
Jong Hyun Kim ◽  
Chang Hun Rhee ◽  
Young Soon Kang ◽  
Je Ho Lee ◽  
...  

Medicines ◽  
2020 ◽  
Vol 7 (3) ◽  
pp. 12
Author(s):  
Akshay Anand ◽  
Gurkeerat Kaur ◽  
Sridhar Bammidi ◽  
Deepali Mathur ◽  
Priya Battu ◽  
...  

Background: The deprivation of oxygen reaching the tissues (also termed as hypoxia) affects the normal functioning of the body. This results in development of many diseases like ischemia, glaucoma, MCI (Mild Cognitive Impairment), pulmonary and cerebral edema, stress and depression. There are no effective drugs that can treat such diseases. Despite such failure, alternative interventions such as mind-body techniques (MBTs) have not been adequately investigated. Methods: The first part of this review has been focused on philosophical aspects of various MBTs besides evolving an ayurgenomic perspective. The potential of MBTs as a preventive non-pharmacological intervention in the treatment of various general and hypoxic pathologies has been further described in this section. In the second part, molecular, physiological, and neuroprotective roles of MBTs in normal and hypoxic/ischemic conditions has been discussed. Results: In this respect, the importance of and in vivo studies has also been discussed. Conclusions: Although several studies have investigated the role of protective strategies in coping with the hypoxic environment, the efficacy of MBTs at the molecular level has been ignored.


2014 ◽  
Vol 568-570 ◽  
pp. 359-362
Author(s):  
Dong Heng Zhang ◽  
Xiu Lin Xu ◽  
Xu Dong Guo

To improve the muscle function handicap and enhance the body movement function of the stroke patients, a new medical instrument, based on audio-visual feedback, is developed. The designed stimulator regards sound (voice) and light signal (flash lamp) as the command signals. With remind of both voice and visualization signal, trainers can take the initiative to participate in training and try their best to generate a weak electromyographic signal. It provides a new treatment platform for stroke patients, which can play a positive role in the rebuilding of cerebral nerve net, the rehabilitation of body movement function diseases, the protection of brain function and psychological rehabilitation. The real-time monitoring and regulating function for the stimulating current was innovatively achieved. With the above functions, it’s easy for doctors to set up different stimulating intensities for different patients. This stimulator also has advantages of safer noninvasive, easy to carry and advanced human-computer interaction function, all of these make contributions to building up the muscle strength and the rehabilitation of body movement.


Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 817
Author(s):  
Tsuyoshi Yamamoto ◽  
Yahiro Mukai ◽  
Fumito Wada ◽  
Chisato Terada ◽  
Yukina Kayaba ◽  
...  

The development of clinically relevant anti-microRNA antisense oligonucleotides (anti-miRNA ASOs) remains a major challenge. One promising configuration of anti-miRNA ASOs called “tiny LNA (tiny Locked Nucleic Acid)” is an unusually small (~8-mer), highly chemically modified anti-miRNA ASO with high activity and specificity. Within this platform, we achieved a great enhancement of the in vivo activity of miRNA-122-targeting tiny LNA by developing a series of N-acetylgalactosamine (GalNAc)-conjugated tiny LNAs. Specifically, the median effective dose (ED50) of the most potent construct, tL-5G3, was estimated to be ~12 nmol/kg, which is ~300–500 times more potent than the original unconjugated tiny LNA. Through in vivo/ex vivo imaging studies, we have confirmed that the major advantage of GalNAc over tiny LNAs can be ascribed to the improvement of their originally poor pharmacokinetics. We also showed that the GalNAc ligand should be introduced into its 5′ terminus rather than its 3′ end via a biolabile phosphodiester bond. This result suggests that tiny LNA can unexpectedly be recognized by endogenous nucleases and is required to be digested to liberate the parent tiny LNA at an appropriate time in the body. We believe that our strategy will pave the way for the clinical application of miRNA-targeting small ASO therapy.


2015 ◽  
Vol 129 (4) ◽  
pp. 314-320 ◽  
Author(s):  
J P Hughes ◽  
G Alusi ◽  
Y Wang

AbstractBackground:Viral gene therapy is a promising new treatment modality for head and neck cancer. This paper provides the reader with a review of the relevant literature in this field.Results:There are government licensed viral gene therapy products currently in use for head and neck cancer, utilised in conjunction with established treatment modalities. The viruses target tumour-associated genes, with the first licensed virus replacing p53 gene function, which is frequently lost in tumourigenesis. Oncolytic viruses selectively destroy cancer cells through viral replication and can be armed with therapeutic transgenes.Conclusion:Despite considerable advances in this field over the last 40 years, further research is needed to improve the overall efficacy of the viruses and allow their widespread utilisation in the management of head and neck cancer.


World Science ◽  
2020 ◽  
Vol 1 (6(58)) ◽  
pp. 32-37 ◽  
Author(s):  
Olga Bilan ◽  
Iryna Brubaker ◽  
Kateryna Marchenko-Tolsta

The review investigates the latest developments in the field of application of nanotechnologies in the transportation of therapeutic agents, features and the advantages of using nanoscale drug delivery systems for the treatment of diseases, as well as further prospects of using this field in medicine. Modern drug delivery systems are characterized by target orientation, rapid response to the environment and the use of biocompatible and biodegradable nanomaterials which allow for the development of the next generation of more effective drugs. Interdisciplinary research in this fast-growing field provides opportunities to design and develop multifunctional devices that can accurately target and successfully administer the release and distribution of active ingredients in the body.


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