Nobel Prize in Chemistry  for 2004 – Appreciation of Controlled, Ubiquitin-Dependent
Protein Degradation

Summary: In the article three Nobel laureates in chemistry for 2004 and their achievements are presented. Their discovery of the first described function of ubiquitin, namely its participation in the controlled protein degradation is shortly reviewed. Moreover, the role of ubiquitin in the regulation of other cellular processes is shown.

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Autophagy – the Tool of Cancer Cell Survival or Death?

Summary: In the last decade a progress has been achieved in understanding the mechanisms which control the cell death. Accumulating evidence suggest that apoptosis is not the only one type of programmed cell death (PCD). Cells use different pathways to active self-destruction process. There are three types of programmed cell death (PCD): condensation prominent, type I or apoptosis, dependent on the activity of caspases, type II-autophagy prominent and type III occurring through disintegration of cells into fragments without condensation and involvement of lysosomal system. Autophagy is a philogenetically very old process, usually considered as a route of cellular proteins degradation and organelle turnover, comprising macroautophagy, microautophagy and chaperone-mediated autophagy. APG and AUT genes regulate this process in mammalian cells. Beclin 1, a homolog of the yeast autophagy protein Atg6 is required for vacuolar transport and can induce autophagy in human cells. Another one homolog of yeast Atg8 gene codes the microtubule-associated protein I (MAP I) light chain 3 (LC3) which exists on the autophagosomes and is currently the only reliable biochemical marker of autophagosomes. Autophagy is beneficial for the maintenance of the balance between the biosynthesis and catabolism of macromolecules and cell survival. On the other hand, autophagy is also involved in elimination of cancer cells by triggering a non-apoptotic cell death program (PCD II), indicating its inhibitory role in tumor development. This article reviews current knowledge on the role of autophagy in cancer cells and its dual function as a tool of cell protecting or killing. Authors emphasized molecular  links between apoptosis and autophagy in tumor cells and possibility of their control for progression in anticancer therapy

Key words: apoptosis, autophagy, beclin1, cathepsin, BID, MAP I LC3, cancer cells.  

Role of STAT Proteins in Inflammatory Bowel Diseases and Colon Carcinogenesis

Summary: STAT mediators comprise a family of seven proteins, that play a key role in intracellular signaling. They are involved in cell differentiation, proliferation and cell death. This article presents a description of STAT proteins with a focus on their probable role in pathology of alimentary system, particularly inflammatory bowel disease and colon carcinogenesis. In inflammatory bowel disease action of STAT3 STAT1 STAT 4 predominates. STAT1 and STAT3 play remarkable roles in colon carcinoma. It was discovered that STAT1 blocks cell proliferation in cell lines of colorectal cancer. An increased expression of STAT3 correlates with clinical staging and nodal involvement. In other malignancies there are described actions of STATs, that analogously might occur in colorectal carcinoma, but that sort of suggestions should be verified in the future studies of this neoplasm. By means of inhibition of STAT proteins, new possibilities of anticancer therapy emerge. This review shows that STAT can interact with other factors in development of colorectal cancer. However, a precise definition of these reactions belongs to the future.

Key words: STAT proteins, inflammatory bowel diseases, carcinogenesis.  

Nucleotide Metabolism in Higher Plants

Summary: Nucleotides are among the most important compounds in all living organisms. They participate in many biochemical processes in cells. They are precursors for nucleic acid synthesis, an energy source and precursors for components of primary and secondary metabolic products. Therefore, the metabolism of nucleotides are crucial for the growth and development of all organisms. In the present review we have concentrated on nucleotides' metabolism and physiological aspects of these processes during different morphogenetic processes, including embryo maturation and seed germination, storage organ development, sprouting and growth of cultured plant cells. The effects of environmental factors on nucleotide metabolism are also described.

Key words:  higher plants, metabolism, nucleotides, plant development, purines, pyrimidines.
 

Neuroblastoma – the Significance of Cytogenetic and Molecular Factors in the Assessment of  the Strategy of  Treatment and  Prognosis

Summary: This review discusses recent advances in the understanding of the biology of neuroblastoma, particular attention is paid to the emerging molecular and cytogenetic factors used to determine the strategy of treatment and prognosis in patients with this tumour. In addition, the genetic model of neuroblastoma development and its application in the process of stratification of patients into risk groups is presented.

Key words: neuroblastoma, prognostic factors, chromosomal aberrations, MYCN amplification, apoptosis, multidrug resistance genes, telomerase, neurotrophin receptors, tumour suppressor genes.  

Human Cytomegalovirus (HCMV) – Latency and Immune Evasion

Summary: Human cytomegalovirus (HCMV) has ability to lifelong maintenance within the host using mechanisms involved in latency. Virus can reactivate and during reactivation HCMV uses different mechanisms (inhibition of antigen presentation, influence on cytokine network, inhibition of NK cells, disturbance of apoptosis) which downregulate effectiveness of immune cells.

Key words: HCMV, latency, reactivation, immune system.

Neuropeptide B (NPB) and Neuropeptide W (NPW) and their Receptors – their Distribution and  Role

Summary: GPR7 and GPR8 (G-protein-coupled Receptors) are two recently discovered and structurally related orphan receptors linked to protein G. They are present both in central nervous system and in peripheral organs. Recently, endogenous ligands of these receptors have been identified. One of them is a 29 amino acid residues long, uniquely modified with bromine and, thus, termed the neuropeptide B (NPB). The other, neuropeptide W (NPW), has been identified in two molecular forms of, respectively, 23 and 30 amino acids (NPW23 and NPW30). Amino acid sequence of NPW23 is identical with first 23 N-terminal amino acids of NPW30. Distribution of the gene expression within the brain suggests that NPB plays a role in feeding control, in control of the neuroendocrine axis, as well as in memory and learning processes. NPW, in turn, affects alimentation, stimulates prolactin secretion and regulates function of the hypothalamic-pituitary-adrenal axis.

Key words: neuropeptide B (NPB), neuropeptide W (NPW), orphan receptors, biological role.
 

Perspectives of Application of Immunotherapy in Neuroblastoma Treatment

Summary: Neuroblastoma is the most common extracranial tumour of childhood. Despite of the application of intensive treatment regiments, the majority of high-risk patients are eventually relapsing. This stresses the need for new therapeutical approaches to eradicate residual tumour cells, which might improve the survival of the high-risk group neuroblastoma patients. Immunotherapy of neuroblastoma is one of the currently developed strategies. In this publication recent data on application of immunotherapy in neuroblastoma treatment have been reviewed. They include the publications investigating neuroblastoma interactionswith immune system. Clinically tested and pre-clinically developed approaches engagingthe immune system to fight the tumour have been reviewed. They include dataon development of the passive and active therapies targeting a neuroblastoma antigen GD2 ganglioside, as well as application of modified tumour cells and dendritic cells as vaccines.

Keywords:  neuroblastoma, immunotherapy, monoclonal antibody, GD2 ganglioside.  

Haematological Malignancies in Older Patients

Summary: In the near future increasing number of elderly patients with haematological malignancies will require chemotherapy and/or radiotherapy. The high dose or even standard chemotherapy usually results in higher, than in younger patients, percentage of life-threatening myelosupression and deaths. This phenomenon in elderly patients is not clear. There are reports suggesting that in elderly patients age-related changes are not so different comparing to younger subjects. In elderly patients anti-tumour response is reduced but function of dendritic cells in these patients is preserved. It seems that cell-based immunotherapy might be a promising therapeutic option for age-advanced cancer patients. In this paper we shortly reviewed some age-specific haematological malignancies.

Key words: haematological malignancies, elderly patients, therapeutic options. 

  [Postepy Biologii Komorki 2005; 32: 115–124]

Aging of  Erythrocyte System and Anemia in the Elderly

Summary: Increasing rate of aged people in societies of developed countries is inevitably connected with occurrence of health problems closely related to this period of life. Ageing as well as old age itself, being a stage of life, are associated with coexisting involutional changes in organs, systems of organs, and old age diseases, accompanying this period of life. In physiological ageing process the disorders mainly concern haematopoesis, especially in conditions of so called hematological stress. It influences the limitations in bone marrow compensation abilities concerning quick leveling of peripheral blood deficits in case of increased demand. It can be connected with telomer hypothesis of ageing. Moreover, the quantitative and qualitative changes in stem cell population are influenced by mutually related factors such as: gene mutations, oxidative stress, uncontrollable apoptosis, regulative disorders of cytokine production. Ageing may also influence the structural changes of erthrocytary membranes, intensification of catabolic processes, and decreased erythropoietin production in kidneys.In aged people, the listed factors are conductive to develop anemies of various etiology. These frequent haematopoietic system diseases, significantly increasing morbidity and mortality in this age group, often result in cardiovascular system diseases, cognitive functions disorders, functional disorders, and fall-downs. They negatively influence the quality of life, however the diagnosis and therapy of old age anemia is a complex geriatric problem.

Key words: ageing, haematopoesis, erythrocyte, cytokines, oxidative stress, anemia.
 

Age-Dependency of the Tolerance of Oncohematological Treatment

Summary: Organism tolerance of very active drugs and aggressive methods of treatment (such as those used in hematology and oncology) is dependent both on age and the possible presence of comorbid disorders. On the other hand, the frequency of these disorders increases with age, so these parameters are statistically (but not always individually) related. Another problem that may influence the analysis is the possible discrepancy between biological and nominal age in particular patients. Furthermore, the tolerance is also dependent on particular tumor present in given patient. Depending on the type of treatment under consideration different are reasons for toxicity increasing with age. With regard to chemotherapy this is increasing with age general susceptibility of internal organs to injury combined with reduced regeneration potential. With regard to bone marrow transplantation it is increased risk of severe graft versus host disease related to thymic involution and with regard to monoclonal antibodies and other immunosuppressive drugs is lowered capacity of immune system to recovery leading to protracted immunodeficient status. However, except for patients heavily pretreated with chemotherapeutic drugs there is no impaired hematopoietic regeneration in older people.
Final conclusion is, that intensive chemotherapy is contraindicated in people older than 70 ± 5 years (depending on comorbidities), autologous stem cell transplantation is contraindicated in patients older than 65 ± 5 years in myeloma and 60 ± 5 years in acute leukemias. Allogeneic transplantation from HLA-identical family donor has upper age limit 55 ± 5 years while allogeneic transplantation from unrelated donor has upper age limit 45 ± 5 years.

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The Quantitative and Qualitative Analysis of The Peripheral Blood Leukocytes  in Centenarians in Comparison to the Healthy Younger Subjects  

Summary: The aim of the study was to characterize the leukocytes (L) from the peripheral blood of centenarians.The study involved 39 subjects aged 100 years and older (group S � 33 females and 6 males) as well as 40 young healthy individuals aged 20�30 years (group K � 35 females and 5 males). In all of them, the quantitative and qualitative analysis of L from blood smear was performed. Additionally, in centenarians, the relationship between the diameter of L and selected serum parameters was studied (vitamin B12, folic acid, iron, C-reactive protein).The mean WBC count as well as mean neutrophils (N) count and limphocytes (L) count were lower in group S than in group K (p<0.05). Oppositely, the mean monocytes (M) count was higher in group S (p<0.001). The diameter of all analyzed L (N, L, M) in group S was higher in comparison to group K (p<0.0001). There was no relationship between the diameter of analyzed leukocytes and the levels of studied biochemical  serum parameters.In conclusion, in centenarians the quantitative and qualitative alterations in peripheral blood leukocytes were found. Further studies are necessary to explain their pathomechanism.

Key words:  centenarians, leukocytes, aging.

[Postepy Biologii Komorki 2005; 32: 137–138]