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Petkova R.,Scientific Technological Service STS Ltd. | Tsekov I.,Military Medical Academy | Yemendzhiev H.,University Professor Dr. Assen Zlatarov Burgas | Kalvatchev Z.,Military Medical Academy
Biotechnology and Biotechnological Equipment | Year: 2012

The rate of infection with human papillomavirus (HPV) worldwide is about 80% of the adult population. Anogenital HPV infections are usually transient and cause no lasting damage. In about 15-20% of the cases, however, the HPV infection may persist and in about 1% it may cause transformation of the infected epithelium that might subsequently progress to overt cervical cancer. The hallmark of the malignant transformation is the integration of the viral genome into the host cell genome, resulting in upregulation of the transcription of the viral oncoproteins E6 and E7. The latter are expressed early in the course of the infection, interacting with the major regulators of the cell cycle progression so as to retain the host cell in a state favourable for the replication of the viral genome. Among the crucial cellular partners in the neoplastic transformation of HPV-infected cells are tumour-suppressor proteins such as p53 and pRb, products of protooncogenes such as p21/WAF1, chromatin structure modifiers such as HMGA1, and controllers of the cellular senescence such as the telomerase complex. The high-risk types of HPV seem to have developed mechanisms capable of evading or disabling virtually any defence. Nature has put in place against cancerous transformation, which could account for the high incidence of cervical dysplasia and cervical cancer despite the efforts the modern medicine and healthcare puts into screening programmes, prevention and therapy. The role of the deregulation of the expression of each of these groups of participants in the pathogenesis of activation of persistent dormant infection is reviewed and their impact on the risk for progression to higher grades of cervical intraepithelial neoplasia (CIN) and development of cervical cancer is assessed.

Petkova R.,Scientific Technological Service STS Ltd. | Chelenkova P.,Sofia University | Tournev I.,Medical University-Sofia | Chakarov S.,Sofia University
Biotechnology and Biotechnological Equipment | Year: 2016

Neurons in the adult central nervous system (CNS) are subjected to high levels of oxidative damage that is usually promptly repaired. Transcribed genomic regions are repaired with priority over untranscribed regions. The prioritization of DNA repair in neurons results in modification of the input into the assessment of genomic integrity in order to delay or avoid damage-related apoptosis unless the damage interferes directly with the functioning of the neuron. CNS neurons may be replaced, albeit rarely. Over-stimulation of adult neural progenitor niche caused by accelerated neuronal loss may result in its premature depletion. The combination of the two pathologic mechanisms (increased rates of neuronal death and depletion of the progenitor niche) may eventually result in irreversible loss of specific cell populations in the CNS and/or generalized neuronal loss. Here we propose that the risk of developing sporadic late-onset neurodegenerative disease (LONDD) may be modulated by the individual capacity for detection and repair of DNA damage and the genetic propensity to repair moderate-degree damage or to assess it as irreparable and route the cell towards apoptosis. Thus, subtly deficient DNA damage repair coupled with a tendency to repair the damage rather than kill the damaged cell may be associated with increased risk of cancer, whereas deficient DNA repair coupled with a propensity to destroy damaged cells may increase the risk of LONDD. Extensive studies of individual repair capacity may be needed to test this hypothesis and, potentially, use the results in the assessment of the risk of common late-onset disease. © 2016 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis.

Petkova R.,Scientific Technological Service STS Ltd. | Chelenkova P.,Scientific Technological Service STS Ltd. | Yemendzhiev H.,University Professor Dr. Assen Zlatarov Burgas | Tsekov I.,Military Medical Academy | And 2 more authors.
Biotechnology and Biotechnological Equipment | Year: 2013

HPV infection is a major pathogenetic factor in cervical carcinoma as well as in many of the squamous cancers of head and neck and other epithelial cancers. Persistence of HPV DNA detectable by routine methods is considered to be a risk factor for advanced CIN and, in patients treated by surgery or non-surgical treatment modalities (radiotherapy, chemotherapy), HPV persistence is believed to be associated with increased risk for local recurrence. In terms of survival, however, it has been repeatedly proven that patients with cervical cancer and other HPV-associated cancers with detectable HPV DNA tend to have better outcomes than patients with HPV-negative tumours. The P72R polymorphism in the human TP53 gene has been contemplated as an independent phenotype modifier in cancers, especially the R allele which has been shown to confer higher pro-apoptotic properties to the resultant p53 protein. It has been demonstrated, however, that RR homozygotes were much more common in study groups with HPV-associated tumours than the other two genotypes and that the P allele in P/R heterozygotes was preferentially lost while the R allele was preferentially retained and mutated. It is possible that HPV-dependent carcinogenesis strictly relies on the presence of HPV and the expression of the E6 and E7 oncoproteins only in the initial phases of transformation of infected cells (e.g. CIN). It may be associated with activation of latent HPV that would create a background of decreased control over the integrity of the genome of the host cell. The process can develop further by mechanisms independent of the presence of HPV and if the virus clears at some later point, that would not halt the already ongoing neoplastic transformation. Absence of HPV DNA in cervical tumours, whether before or after treatment, is not a reason to decrease vigilant monitoring and rule out the need for further treatment, as it may be quite possible that the TP53 gene of the infected cells has already been modified in the course of cancer progression by HPV-independent mutagenesis. Cervical tumours that are HPV-negative ought to alert attending oncologists for the possibility for increased growth potential and invasiveness of the tumour so as to contemplate more aggressive anticancer therapies, especially in carriers of the R allele of the P53R polymorphism. © Biotechnol. & Biotechnol.

Chakarov S.,Sofia University | Petkova R.,Scientific Technological Service STS Ltd | Russev G.C.,Bulgarian Academy of Science
Biotechnology and Biotechnological Equipment | Year: 2012

p53 is a master regulator of the cell cycle, capable of assessing the severity and the scope of damage to the cellular DNA, integrating the signals from the cell under stress and delivering the final decision about the destiny of the cell - undertaking repair activities; entering replicative senescence; inducing cell death; resorting to translesion transactions or altering the metabolism or the expression pattern of the cell. Proper functioning of p53 and its related pathways is essential in multicellular eukaryotes, with failures in the DNA-binding and transactivation properties of p53 usually resulting in cancer. Recent research on some common polymorphic variants of p53 that exhibit differential properties in their ability to induce cell cycle arrest or apoptosis indicate that p53 is not only the 'guardian angel' of the genome, as is commonly believed, keeping its integrity in check and disposing of damaged cells, but it is as well the 'archangel' that is responsible for cutting down the lifespan of the organism by the mechanism of ageing. One function can hardly exist without the other, and it is very individual as to whether carriership of one polymorphic form or another would be beneficial in the particular case, considering the general status of the patient and the specificities of the pathogenesis of the disease or condition in question. Age of the patient seems to be a major determining factor, as the differential pattern in the properties of p53 seems to become more pronounced as age advances.

Chelenkova P.,Scientific Technological Service STS Ltd. | Petkova R.,Scientific Technological Service STS Ltd. | Yochev S.,Bulgarian Ichthyological Society | Vasilev M.,Bulgarian Academy of Science | Chakarov S.,Sofia University
Biotechnology and Biotechnological Equipment | Year: 2011

Brown trout (Salmo trutta fario) is a popular object of recreational fishing in Bulgaria and throughout Europe. Free-living ('wild') populations of brown trout are seen in many cold water rivers, and restocking of artificial as well natural water basins is carried out routinely. Genetic analysis for a microsatellite marker common for several salmonid species but discriminative in regards to species affiliation shows that allele lengths uncharacteristic of brown trout but typical of Atlantic salmon may be observed in Bulgarian 'wild' populations of brown trout. It is possible that a subpopulation containing interspecies hybrids with Atlantic salmon exists in the Bulgarian water basins populated with brown trout. Since brown trout-salmon hybrids have been shown to be viable and fertile, the possibility for future interspecies introgression cannot be ruled out. The biodiversity of Bulgarian natural populations of salmonid fishes may benefit from a more finely tailored stocking strategy.

Khalil H.S.,University of Abertay Dundee | Petkova R.,Scientific Technological Service STS Ltd | Zhelev N.,University of Abertay Dundee
Biotechnology and Biotechnological Equipment | Year: 2012

Human society ages at a steady rate, that is, the proportion of adult and elderly individuals increases constantly because of improved living conditions and the advances in medical care. This means that very soon the tradeoff between the advantages in old age conferred by alleles disadvantageous or neutral in young age would begin to show, providing the fascinating opportunity of studying the interplay between genetic factors and environment outside the framework of reproductive capacity and in the unique milieu of the aging cell. Being healthy and/or health-conscious in youth does not guarantee for successful aging or even that the person would live up to the average life expectancy of the population. Therefore, successful aging and longevity are related to a healthy-conscious attitude to a degree only. The present paper reviews the basic genetic and evolutionary mechanisms which have operated during human history so as to ensure survival of humankind and the possible factors preventing or contributing to successful aging.

Petkova R.,Scientific Technological Service STS Ltd. | Chicheva Z.,Scientific Technological Service STS Ltd. | Chakarov S.,Sofia University
Biotechnology and Biotechnological Equipment | Year: 2011

Telomeres are ribonucleoproteid complexes capping the ends of linear genomes and protecting them from attrition and fusion. The rate of telomere shortening is related to cellular aging and a loss of telomere length is observed in a significant proportion of human diseases and conditions. Telomerase activity may serve as a useful marker for capacity for self-renewal and potential for differentiation in stem cells. The present paper reviews the present-day methods for measuring telomere length in cell populations and/or assessment of telomerase activity - Southern hybridisation, flow cytometry/Flow FISH, real-time PCR and some less popular methods such as TRAP analysis and STELA, assessing the advantages and weaknesses of each method and outlining the possible fields of application.

Chicheva Z.,Scientific Technological Service STS Ltd. | Chelenkova P.,Scientific Technological Service STS Ltd. | Petkova R.,Scientific Technological Service STS Ltd. | Chakarov S.,Sofia University
Biotechnology and Biotechnological Equipment | Year: 2012

The DNA repair machinery of healthy human cells usually manages the consequences of the daily barrage of DNA damage for years and decades before any adverse effects related to genotoxic impact become manifest. There is significant variance, however, even between healthy individuals, in regard to their ability to detect and repair genotoxic damage. Some aspects of this variance exist throughout the life of the individual (genetic factors, such as polymorphisms in genes coding for products acting in the repair of DNA damage), while others (e.g. telomere length) may be the outcome of the genotype-phenotype interplay, modified by environmental factors. Numerous markers for assessment of capacity to combat genotoxic damage have been described so far, with only some of them having a value of their own under physiological and/or pathological conditions. In the present study we provide the results from the evaluation of a mini-panel (p53 P72R, XPCins83PAT, rate of telomere attrition) for assessing the capacity of healthy individuals to repair genotoxic damage, and outline the possible fields of application.

Petkova R.,Scientific Technological Service STS Ltd. | Chakarov S.,Sofia University
Biotechnology and Biotechnological Equipment | Year: 2016

The mechanisms for identification of DNA damage and repair usually manage DNA damage very efficiently. If damaged cells manage to bypass the checkpoints where the integrity of the genome is assessed and the decisions whether to proceed with the cell cycle are made, they may evade the imperative to stop dividing and to die. As a result, cancer may develop. Warding off the potential sequence-altering effects of DNA damage during the life of the individual or the existence span of the species is controlled by a set of larger checkpoints acting on a progressively increasing scale, from systematic removal of damaged cells from the proliferative pool by means of repair of DNA damage/programmed cell death through ageing to, finally, cancer. They serve different purposes and act at different levels of the life cycle, safeguarding the integrity of the genetic backup of the individual, the genetic diversity of the population, and, finally, the survival of the species and of life on Earth. In the light of the theory that cancer is the final checkpoint or the nature's manner to prevent complex organisms from living forever at the expense of genetic stagnation, the eventual failure of modern anti-cancer treatments is only to be expected. Nevertheless, the medicine of today and the near future has enough potential to slow down the progression to terminal cancer so that the life expectancy and the quality of life of cancer-affected individuals may be comparable to those of healthy aged individuals. © 2016 The Author(s). Published by Taylor & Francis.

PubMed | Sofia University and Scientific Technological Service STS Ltd.
Type: Journal Article | Journal: Biotechnology, biotechnological equipment | Year: 2015

The concept of pluripotency as a prerogative of cells of early mammal embryos and cultured embryonic stem cells (ESC) has been invalidated with the advent of induced pluripotent stem cells. Later, it became clear that the ability to generate all cell types of the adult organism is also a questionable aspect of pluripotency, as there are cell types, such as germ cells, which are difficult to produce from pluripotent stem cells. Recently it has been proposed that there are at least two different states of pluripotency; namely, the nave, or ground state, and the primed state, which may differ radically in terms of timeline of existence, signalling mechanisms, cell properties, capacity for differentiation into different cell types, etc. Germ-like male and female rodent cells have been successfully produced

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