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The probable role of stem cells has been presented in the development of tumors. It has been stressed that in contrast to immature, capable of proliferation and undifferentiated cells, the mature cells are unable to yield a neoplastic clone. The existence of cell clones or subclones determines the extent of differentiation in tumor cells and, thus, results in the heterogeneity of the tumor. Biological activity of such tumors involves production of several substances which negatively affect the organism of the host.
Papillomaviruses (PV) are small, nonenveloped, DNA viruses, which had originally been grouped together with the Polyomaviruses in one family, Papovaviridae. In the year 2004 the International Committee on the Taxonomy of Viruses officially recognized two separate families: Papillomaviridae and Polyomaviridae. PV are pathogens of skin and mucosa in animals and humans, and they are very species-specific. The only known case of cross-species infection is the infection of horses by bovine papillomaviruses (BPV) type 1 and 2. Infection by high-risk types of human papillomaviruses (HPV) such as HPV type 16 and 18 is directly related to the subsequent development of cervical carcinoma in women. In the year 1995 The International Agency for Research on Cancer officially declared, that HPV-16 and HPV-18 are carcinogenic for humans. Animal PV cause various diseases in both farm and companion animals, e.g. skin and teat papillomatosis in cattle, canine oral papillomatosis, oesophageal papillomas and carcinoma in cattle and equine sarcoids. The mechanisms of carcinogenesis caused by PV were initially established using animal models and specifically chosen PV, particularly cottontail rabbit papillomavirus (CRPV), BPV and canine oral papillomavirus (COPV). In the paper the organization and structure of the PV genome, the characteristics of early and late regions, enzymatic and regulatory proteins, encoded by specific open reading frames and engaged in virus replication process, as well as structural proteins that take part in virus-cell interaction have been discussed. The replication process of PV and mechanisms of carcinogenic transformation of cells infected with PV were also described. The possibility of the implementation of specific immunoprophylaxis and the necessity of improvement of diagnostic methods, as well as conducting molecular comparative studies of human and animal PV, important for the protection of animal health and public health, have been indicated.
There is a specific antagonism between an aging organism and neoplasia, in which the tumor is considered to influence the local tissue. It returns to some atavistic features, including the thermodynamic approach (2nd law of thermodynamics, Fig. 1), causing the rejuvenation of the surrounding tissue. The existence of various theories of oncogenesis entitles their supplementation with the theory of inflammaging: an entropic inflammation that can potentially have an indirect influence on the oncogenesis. This theory covers the effects of various causes of aging, including genetically programmed changes, telomere dependent processes and damage of genome, epigenome and proteome particles. The paper describes the patomechanism of inflammaging, including the role of mitochondria (point mutations and deletions especially in mtDNA), oxidative stress with overproduction and accumulation of free radicals and NFkB factor (nuclear factor kappa-light chain-enhancer of activated B cells) and the possibility of the influence of inflammaging on oncogenesis (Fig. 2). The inflamma-ging is programmed by hypothalamus using the immune-neuro-endocrine system, including gonadotropin releasing hormone (GnRH) that inhibits the NFkB factor with the inactivation of kinase IKK-beta. Regardless of that, the chronic inflammation, exceeding its defensive competence, lasts for years and can also be the beginning of neoplastic cells proliferation.
Senescence of the organism is a consequence of several molecular (induction of proapoptotic genes expression, DNA damage) and biochemical changes, which gradually leads to the degeneration of some systems and organs. One of the most important features of progressive senescence is also a decreased response of the immunological system (proinflammatory response), which may result in a higher susceptibility to infection. The process of oncogenesis is closely associated with the age of an animal and progressive senescence. However, the proper assessment of the association between the induction of oncogenesis and senescence is problematic, mainly with regards to several species specific features like the weight of a dog or its breed. Moreover, the association between the activity of the immunological system and oncogenesis in a dog in an age-dependent manner is also unclear. Studies have suggested that the main factors which influence the process of senescence and oncogenesis are: DNA damage, spontaneous mutations, increase of oxidative stress and decrease of immunological system activity. In this article, the mechanisms and factors associated with oncogenesis and canine senescence have been presented. The authors have also described the role of selected proteins in the induction of these processes.
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