Wyniki wyszukiwania - Biblioteka Nauki

1

Malformations of angiogenesis in the low differentiated human carcinomas. Immunohistochemical study

100%

Zoltowska A. , Stepinski J. , Lewko B. , Zamorska B. , Roszkiewicz A. , Serkies K. , Kruszewski W.

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2001

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tom 49

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nr 1

59-62

EN

Our previous observations showed that the perivascular mesenchyma of the thin-walled vessels (capillaries) in cancers may be the source of organ-specific stem cells. We suggested that the cells forming vascular channels in altered stroma participate in the tumor development. This study was designed to examine the distribution of the vessels and their appearance in the breast, lung and colon cancers. Using immunohistochemical methods, we have shown that in the low differentiated tumors both CD31 and factor VIII antigens may be expressed in capillaries chiefly on the periphery of neoplastic foci. Many of these vessels were discontinuous, with interruptions or unformed tubules. Sporadically, CD31 protein and factor VIII antigens were not expressed in capillaries inside the very low differentiated cancer cases. It is difficult to assess by immunohistochemichal means whether the vascular malformations are the primary or secondary phenomena in the malignancy and why these abnormalities were especially visible in some low differentiated cancers.

2

Heterocyclic aromatic amines and their role in the induction of carcinogenesis

100%

Woziwodzka A. , Piosik J.

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2009

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nr 4

133-151

EN

Cancer is one of the most frequent causes of human death worldwide. It is a consequence of inherited DNA impairments or mutations induced by several exogenous factors. Diet is one of the most important exogenous factors, which is responsible for one-third cancer incidents in humans. Heterocyclic aromatic amines (HCA) arise during thermal processing of food. Based on the results on rodents and epidemiological data IARC classified HCA as probably (class 2A) or possibly (class 2B) carcinogenic to humans. After metabolic activation by cytochrome P450, N-hydroxy derivatives of HCA demonstrate strong mutagenic activity as they can form adducts with DNA. Experiments on laboratory animals indicated that HCA induce digestive tract, breast and lung cancers. Epidemiological data also confirm the association between HCA consumption and cancer appearance in humans. Although it is impossible to completely eliminate HCA from diet, there are several ways to limit the exposure to HCA and decrease their negative impact on human organisms.

3

Role of response gene to complement 32 in disease

100%

Vlaicu S. I. , Cudrici C. , Ito T. , Fosbrink M. , Tegla C. A. , Rus V. , Mircea P. A. , Rus H.

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2008

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tom 56

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nr 2

115-122

EN

The role of response gene to complement (RGC)-32 as a cell cycle regulator has been attributed to its ability to activate cdc2 kinases and to induce S-phase entry and mitosis. However, recent studies revealed novel functions for RGC-32 in diverse processes such as cellular differentiation, inflammation, and fibrosis. Besides responding to C5b-9 stimulation, RGC-32 expression is also induced by growth factors, hormones, and cytokines. Transforming growth factor ? activates RGC-32 through Smad and RhoA signaling, thus initiating smooth muscle cell differentiation. Accumulating evidence has drawn attention to the deregulated expression of RGC-32 in human malignancies, hyper-immunoglobulin E syndrome, and fibrosis. RCG-32 expression is up-regulated in cutaneous T cell lymphoma and colon, ovarian, and breast cancer, but down-regulated in invasive prostate cancer, multiple myeloma, and drug-resistant glioblastoma. A better understanding of the mechanism by which RGC-32 contributes to the pathogenesis of these diseases will provide new insights into its therapeutic potential. In this review we provide an overview of this field and discuss the most recent research on RGC-32.

4

Nucleotide excision repair, NER - a relationship with cancer risk

100%

Butkiewicz D. , Rusin M. , Pawlas M. , Czarny M. , Chorazy M.

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nr 4

485-498

EN

DNA damage repair, responsible for maintaining the genome integrity, plays a central role in cancer biology. Individual DNA repair capacity is genetically determined. Inherited defect in nucleotide excision repair (NER) genes leads to three distinct and extremely rare disorders: xeroderma pigmentosum, associated with high risk of skin cancer, Cockayne syndrome, and trichothiodystrophy. The recently identified common polymorphism in several NER genes may also influence a risk of cancer in general population. The review presents current knowledge about a role of genetic variation of NER genes in cancer predisposition.

5

Prognostic significance of p53 protein accumulation in cancer cells obtained from selected group of patients with sporadic colorectal cancer

100%

Paluszkiewicz P. , Karski J. , Berbe H. , Pawlowska-Wakowicz B. , Cybulski M. , Karski M. , Paszkowska A.

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tom 40

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nr 2

135-144

EN

p53 gene instability frequently causes accumulation of mutant protein in neoplastic cells. The goal of this study was to evaluate of p53 protein accumulation in tumour cells in relation to colorectal cancer outcome. p53 protein accumulation was tested immunohistochemically using DO-7 and Pab-1620 antibodies. In the group of 80 selected patients with sporadic colorectal cancer, p53 protein accumulation in tumour cells was found significantly more often (52.6% of cases) in cancers localised in the colon, nonmucinous and poorly differentiated. In 5-year follow-up, a shorter survival time was observed in the group of patients with p53 protein accumulation in cancer cells (P<0.05). The differences in p53 protein accumulation found in cancer cells in relation to tumour localisation and their histological type indicate the possibility of p53-independent carcinogenesis in mucinous and right-sided cancers. We indicate the importance of performing the immunohistochemical tests for prediction of the outcome of sporadic colorectal cancers.

6

Cancer stem cells: the theory and perspectives in cancer therapy

100%

Gil J. , Stembalska A. , Pesz K. A. , Sasiadek M. M.

Journal of Applied Genetics

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2008

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tom 49

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nr 2

193-199

EN

The cancer stem cell theory elucidates not only the issue of tumour initiation and development, tumour's ability to metastasise and reoccur, but also the ineffectiveness of conventional cancer therapy. This review examines stem cell properties, such as self-renewal, heterogeneity, and resistance to apoptosis. The ?niche' hypothesis is presented, and mechanisms of division, differentiation, self-renewal and signalling pathway regulation are explained. Epigenetic alterations and mutations of genes responsible for signal transmission may promote the formation of cancer stem cells. We also present the history of development of the cancer stem cell theory and discuss the experiments that led to the discovery and confirmation of the existence of cancer stem cells. Potential clinical applications are also considered, including therapeutic models aimed at selective elimination of cancer stem cells or induction of their proper differentiation.

7

Inhibition of angiogenesis in the treatment of tumors

100%

Ostrowski K. , Kinsner A.

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2001

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tom 49

|

nr 1

27-32

EN

Angiogenesis is essential for tumor progression, growth and metastases. Many substances present in a normal organism can inhibit or stimulate the process of new vessel formation in tumors. The use of natural or synthetic angiogenesis inhibitors as anticancer drugs is currently under intense investigation. Such agents can have lower toxicity and are less likely to generate drug resistance than conventional cytotoxic drugs. Clinical trials are now underway to develop optimum treatment strategies for antiangiogenic drugs. This paper reviews the present achievements in preclinical and clinical studies with antitumor drugs based on inhibitors of angiogenesis.

8

Usefulness of polymorphic markers in exclusion of BRCA1/BRCA2 mutations in families with aggregation of breast/ovarian cancers

88%

Gorski B. , Debniak T. , Jakubowska A. , Cybulski C. , Huzarski T. , Byrski T. , Zlowocka E. , Lubinski J.

Journal of Applied Genetics

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2003

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tom 44

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nr 3

419-423

EN

Founder mutations can account for a large proportion of BRCA1/BRCA2 gene abnormalities in a given population. However there is still a need to study the entire gene in many families, even in countries where founder mutations have been identified. It is possible to decrease the number of cases which are studied by complex and expensive sequencing/Southern blot analyses of BRCA1/BRCA2 genes by exclusion of common BRCA1/BRCA2 alleles in a given family by using polymorphic dinucleotide markers. The goal of our study was to assess the effectiveness of this method in exclusion of BRCA1/BRCA2 constitutional mutations. In each family, blood samples for genetic analyses were taken from two affected relatives from the same generation. Six polymorphic microsatellite markers linked to BRCA1/BRCA2 genes were analysed. Results obtained with these markers were verified by applying BRCA1 testing for the most common founder mutations in Poland and using ?exon by exon? sequencing of coding fragments of the BRCA2 gene. Polymorphic markers useful in BRCA1/BRCA2 analyses included only 3 of 6 examined ? D17S855, D13S260 and D13S267. Occurrence of common alleles of BRCA1 was excluded in 3 families and BRCA2 in 5 out of 30 families. Results obtained by testing for BRCA1 Polish founder mutations and BRCA2 sequencing were in agreement with BRCA1 findings based on polymorphic markers. The only exception was family 994 with BRCA1 exon 5 300T/G mutation, in which BRCA1 mutation carrier was excluded by using D17S855. Among 14 families without BRCA1 Polish founder mutations in this gene were excluded in 2 families and BRCA2 mutation was excluded in one family.

9

Isolation, composition and biological activities of mushroom polysaccharides on the example of Hericium erinaceum

88%

Malinowska E. , Krzyczkowski W. , Herold F.

Biotechnologia

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2008

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nr 1

109-121

EN

In recent years mushroom polysaccharides have been extensively investigated according to their unique biological activity. Among them polysaccharides from Hericium erinaceum (Hydnaceae) are well known as anti-tumor and cholesterol reducing agents as well as growth and differentiation of adrenal nerve cells stimulators. In Poland, H. erinaceum is restricted only to several areas and is considered endangered species. Thus mycelium and culture broth obtained from submerged in vitro culture could be an excellent source of polysaccharides. The review describes methods of isolation, purification and analysis of mushroom polysaccharides and summarizes data about biological activities of Hericium erinaceum polysaccharides.

10

Dendritic cells and their application in cancer immunotherapy - achievements and future prospects

88%

Rossowska J. , Pajtasz-Piasecka E.

Postępy Higieny i Medycyny Doświadczalnej

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2003

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tom 57

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nr 5

501-518

EN

Dendritic cells (DC) are generally believed to play a key role in the initiation of immune response. A potential usefulness of these cells in antitumor immunotherapy is strongly considered in every stage of cancer treatment. Studies on tumor tissue infiltration by immune cells shown, that DC represented only a small percentage of leukocytes. The influence of tumor environment resulted in reduction of DC number, their inability to migrate across endothelial barriers, or impaired maturation and efficiency of tumor antigens presentation. Thus, decreased number of DC in tumors could be associated with a bad prognosis. Many attempts concentrate on the creation of the DC-based vaccines, which would generate strong anticancer cell mediated immunity. They include studies on stage of differentiation of the administered DC; effective way for antigen loading; optimum route and schedule of DC delivery into tumor bearing host; effective vectors for the therapeutic genes; effects of the therapy based on cytokine secreting DC; influence of DC on co-operation between innate and acquired immunity as well as on the generation of specific antitumor response. This review is focused on two important areas aiming for the preparation of DC vaccine for effective stimulation of immune response: - loading of DC with tumor antigens (or other ways of DC preparation to successful antigen presentation) - as an encouraging evidence of therapeutic efficacy, and - genetic modification of DC with cytokines resulting in the stimulation or alteration of the antitumor DC activity - as a promising anticancer strategy.

11

DNA Tumor Vaccines

88%

Wlazlo A. P. , Ertl H. C. J.

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2001

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tom 49

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nr 1

1-12

EN

A new generation of vaccines are being developed to induce immune responses that fight off infectious agents, or erradicate cancerous cells. The new vaccines are based on a plasmid vector, which in transfected mammalian cells cause constitutive high-level expression of the target antigen. Expression of the target antigen, in turn, can induce a full-range of immunologic responses, including cell-mediated killing, cell-mediated cytokine release and the production of antigen-specific antibodies. Through molecular techniques, these nucleic acid vaccines can enhanced to increase target antigen expression and faciliatate antigen presentation. Additionally, genetic adjuvants expressed simultaneously with the target antigens can induce the immune responses to disease-associated antigens. The ease with which these genetic vaccines can be generated and the potency of their ability to generate immune-mediated responses make them highly effective, which creates hope for developing effective treatment and prevention of various diseases, most notably cancer.

12

Fatty acid synthase-catalyzed de novo fatty acid biosynthesis: from anabolic-energy-storage pathway in normal tissues to jack-of-all-trades in cancer cells

88%

Menendez J. A. , Lupu R.

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nr 6

414-426

EN

In 1994, Kuhajda and colleagues unambiguously identified the oncogenic antigen-519, a prognostic molecule found in breast cancer patients with markedly worsened prognosis, as fatty acid synthase (FAS), the key enzyme for the de novo fatty acid biosynthesis. It now appears that human carcinomas and their pre-neoplastic lesions constitutively overexpress FAS and undergo significant endogenous fatty acid biosynthesis. Moreover, FAS blockade specifically induces apoptotic cancer cell death and prolongs survival of cancer xenograft hosts. Therefore, FAS signaling seems to play a central role in the maintenance of the malignant phenotype by enhancing cancer cell survival and proliferation. This review documents the rapidly changing perspectives on the function of FAS in cancer biology. First, we describe molecular mechanism by which aberrant transduction cascades driven by oncogenic changes subvert the down-regulatory effects of dietary fatty acids, resulting in tumor-associated FAS insensitivity to nutritional signals. Second, we speculate on the putative function that hypoxia can play as the epigenetic factor that triggers and maintains FAS overexpression in cancer cells by inducing changes in gene expression and in metabolism for survival. Third, we explore the role that FAS exhibits in cancer evolution by specifically regulating cancer-related proteins such as Her-2/neu oncogene and estrogen receptor. Finally, we reveal previously unrecognized functions of FAS on the response of cancer cells to chemo-, endocrine-, and immuno-therapies. These findings, all together, should ultimately enhance our understanding of how FAS-dependent endogenous fatty acid metabolism, once considered a minor anabolic-energy-storage pathway in normal cells, has become a jack-of-all-trades in cancer cells.

13

The influence of beta-carotene, retinoids, RAR and RXR receptors on proliferation and neoplastic transformation of cells

88%

Staniaszek K. , Gozdzicka-Jozefiak A.

Biotechnologia

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2008

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nr 3

28-45

EN

Beta carotene is a member of a class of substances called carotenoids. Beta carotene, alpha carotene and beta cryptoxanthin can serve as dietary precursors of retinoids (RA, all-trans retinol or provitamin A). Biological effects of retinoids and expression of RA responsive gene are mediated by different receptors, namely RAR and RXR in homodimeric or heterodimeric form. Expression levels of the retinoic acid receptors are significantly different in neoplastic tissues compared with non-neoplastic tissues for many types of tumors.

14

The genes of interferons and interferon-related factors: localization and relationships with chromosome aberrations in cancer

75%

Haus O.

Archivum Immunologiae et Therapiae Experimentalis

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2000

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tom 48

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nr 2

95-100

EN

The paper presents a review of data on the localization of interferons (IFNs) and IFN system genes and their relationship with human diseases, mainly cancer. Genes of interferon system proteins are located at the sites of breakpoints of the structural chromosome aberrations in cancer. Thus, any of them are rearranged or translocated in various tumor types. As the activity of these genes plays a role in cancer development, their rearrangements may be one of the crucial points in the pathogenesis of some cancer types. Besides, they also take part in organism immunity against viral infections. Transfection experiments with IFN system genes have proved the influence of these genes on cancer behavior and may serve as a basis for clinical gene therapy. IFN-alpha and IFN-beta genes are located at 9p21-22, the site of frequent homozygotic deletions in cancer. Their loss sensitizes cells to the growth inhibitory actions of exogenous IFNs. The IFN-gamma gene, a representative of class II genes, is located at 12q24. 1. Transfection of class II IFNs genes to cancer cell lines causes cell proliferation arrest and augments the expression of HLA antigens, which may be clinically useful in stimulating the immune destruction of tumor cells. The interferon regulatory factor 1 (IRF-1) gene is located at 5q31, the site of common deletions in myelodysplastic syndromes (MDS) and secondary leukemias. The loss of heterozygosity of this gene was found in MDS, which proves that IRF-1 may be a tumor suppressor. A transfection of its gene causes neoplastic transformation arrest. The double-stranded RNA-activated protein kinase (PKR) gene is located at 2p21-22, a region which is frequently rearranged in leukemia. Transfection of a wild type PKR gene reverses neoplastic transformation caused by transfection of a mutated PKR gene, proving that PKR acts as a dominant negative cancer suppressor.

15

RELIGIOUS MEANING AND CONTROL IN THE MIDST OF CANCER

75%

Ladd K. L.

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nr 3

169 – 179

EN

The interrelated processes of finding meaning and making control attributions are examined among cancer patients (N = 168) for whom religion is either a non-central (a-schematics, n = 55) or central (schematics, n = 76) aspect in their self-definitions. Various quality of life indices display complex relations to the prediction of the individual’s level of reported experience of finding meaning and control attributions, depending upon schematicity. No single unifying factor is discerned concerning how the two groups experience meaning; initial perceptions of threat appear to be a common theme in relation to how they attribute control. Additionally, a-schematics, as opposed to schematics, report less improvement in their relationships with family and friends as well as less confidence in how they have personally coped with the cancer related experience.

16

Cancer stem cells as targets for cancer therapy: Selected cancers as examples

75%

Hombach-Klonisch S. , Paranjothy T. , Wiechec E. , Pocar P. , Mustafa T. , Seifert A. , Zahl C. , Gerlach K. L. , Biermann K. , Steger K. , Hoang-Vu C. , Schulze-Osthoff K. , Los M.

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2008

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tom 56

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nr 3

165-180

EN

It is becoming increasingly evident that cancer constitutes a group of diseases involving altered stem-cell maturation/differentiation and the disturbance of regenerative processes. The observed malignant transformation is merely a symptom of normal differentiation processes gone astray rather than the primary event. This review focuses on the role of cancer stem cells (CSCs) in three common but also relatively under-investigated cancers: head and neck, ovarian, and testicular cancer. For didactic purpose, the physiology of stem cells is first introduced using hematopoietic and mesenchymal stem cells as examples. This is followed by a discussion of the (possible) role of CSCs in head and neck, ovarian, and testicular cancer. Aside from basic information about the pathophysiology of these cancers, current research results focused on the discovery of molecular markers specific to these cancers are also discussed. The last part of the review is largely dedicated to signaling pathways active within various normal and CSC types (e.g. Nanog, Nestin, Notch1, Notch2, Oct3 and 4, Wnt). Different elements of these pathways are also discussed in the context of therapeutic opportunities for the development of targeted therapies aimed at CSCs. Finally, alternative targeted anticancer therapies arising from recently identified molecules with cancer-(semi-)selective capabilities (e.g. apoptin, Brevinin-2R) are considered.

17

Epigenetic diagnostics of cancer ? the application of DNA methylation markers

75%

Paluszczak J. , Baer-Dubowska W.

Journal of Applied Genetics

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2006

|

tom 47

|

nr 4

361-364

EN

In recent years it has become apparent that epigenetic events are potentially equally responsible for cancer initiation and progression as genetic abnormalities. DNA methylation is the main epigenetic modification in humans. Two DNA methylation lesions coexist in human neoplasms: hypermethylation of promoter regions of specific genes within a context of genomic hypomethylation. Aberrant methylation is found at early stages of carcinogenesis and distinct types of cancer exhibit specific patterns of methylation changes. Tumor specific DNA is readily obtainable from different clinical samples and methylation status analysis often permits sensitive disease detection. Methylation markers may also serve for prognostic and predictive purposes as they often reflect the metastatic potential and sensitivity to therapy. As current findings show a great potential of recently characterised methylation markers, more studies in the field are needed in the future. Large clinical studies of newly developed markers are especially needed. The review describes the diagnostic potential of DNA methylation markers.

18

Tumor markers studied with proteomic methods in blood and serum plasma

75%

Pietrowska M.

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nr 2

39-53

EN

Proteins are major components that directly determine phenotypes of cells and organisms, in either normal or pathological conditions. Because of numerous post-translational events that modify structure and function of proteins, the knowledge of genomes is only at the beginning of understanding of the full complexity of biological systems. 'Proteomics' is the study of proteomes, which addresses proteins' 3D structure, function, and their inter- and intracellular communication. Among primary goals of proteomics, there is discovery of biomarker for various human disease conditions. Plasma and serum are considered to be the source of choice in molecular diagnostics. The development of cancer involves transformation and proliferation of altered cell types that produce unique proteins and enzymes, which can significantly modify the pattern of serum peptides and proteins. The serum protein/peptide profiles that could be registered using different analytical methodologies appear to carry important information with direct clinical applicability. Importantly, such peptide profiles itself could become a new kind of potential tumor marker. These approaches are promising, but the results obtained are still preliminary. For example, detection of disease markers in the blood proteome could be hampered by its extremely low concentrations and the presence of a few abundant components (e.g., albumin and immunoglobulins), and thus development of more specific and sensitive analytical methods is still required. Nevertheless, identification of serum proteomic patterns or molecular signatures specific for different cancer types, stages and responses to therapy is possible at this moment. This article provides a comprehensive overview of current methodologies used for cancer biomarkers detection in blood proteome.

19

Biotechnology to combat reactive oxygen species

63%

Nawrot R. , Gozdzicka-Jozefiak A.

Biotechnologia

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2002

|

nr 2

88-101

EN

Increased generation of reactive oxygen species (ROS) lies at the background of many diseases, including cancer. Numerous experimental data show that ROS play direct and indirect role in induction and promotion of cancer. Antioxidants, such as glutathione, bilirubin, urate, carotenoids, ascorbate, tocopherols, retinol, belong to nonenzymatic protective mechanisms against ROS antioxidents. A number of plants are rich source of egzogenic antioxidants. Genetic engineering methods are used to modify food plants in the hope that it will elevate their antioxidant content. The recent successful developments are -carotene-rich ?golden rice? and tomato. Intake of these plants could contribute to health benefits worldwide.

20

P-selectin mediates adhesion of leukocytes, platelets, and cancer cells in inflammation, thrombosis, and cancer growth and metastasis

51%

Chen M. , Geng J.-G.

Archivum Immunologiae et Therapiae Experimentalis

|

2006

|

tom 54

|

nr 2

75-84

EN

Stimulated endothelial cells and activated platelets express P-selectin (CD62P), a member of the selectin family of cell adhesion molecules, which interacts with P-selectin glycoprotein ligand-1 (PSGL-1, CD162) for leukocyte rolling on stimulated endothelial cells and heterotypic aggregation of activated platelets onto leukocytes. Cross-linking of PSGL-1 by P-selectin also primes leukocytes intracellularly for cytokine and chemoattractant-induced 2-integrin activation for firm adhesion of leukocytes. Furthermore, P-selectin mediates heterotypic aggregation of activated platelets to cancer cells and adhesion of cancer cells to stimulated endothelial cells. Here we provide a comprehensive summary of the functional roles and the biological importance of P-selectin-mediated cell adhesive interactions in the pathogeneses of inflammation, thrombosis, and the growth and metastasis of cancers.