The purpose of this study was to assess and describe the current spectrum of emerging zoonoses between 2000 and 2006 in European countries. A computerized search of the Medline database from January ...1966 to August 2006 for all zoonotic agents in European countries was performed using specific criteria for emergence. Fifteen pathogens were identified as emerging in Europe from 2000 to August 2006: Rickettsiae spp., Anaplasma phagocytophilum, Borrelia burgdorferi, Bartonella spp., Francisella tularensis, Crimean Congo Haemorrhagic Fever Virus, Hantavirus, Toscana virus, Tick-borne encephalitis virus group, West Nile virus, Sindbis virus, Highly Pathogenic Avian influenza, variant Creutzfeldt–Jakob disease, Trichinella spp., and Echinococus multilocularis. Main risk factors included climatic variations, certain human activities as well as movements of animals, people or goods. Multi-disciplinary preventive strategies addressing these pathogens are of public health importance. Uniform harmonized case definitions should be introduced throughout Europe as true prevalence and incidence estimates are otherwise impossible.
Common fragile sites (CFSs) are regions of the genome prone to breakage by replication inhibitors (extrinsic replication stress). Recently, we and others observed that oncogene-induced replication ...stress (RS) induces DNA damage from the earliest stages of cancer. Our aim was to perform a genome-wide analysis in precancerous and cancerous experimental models to examine whether allelic imbalance occurs within CFSs. Subsequently, CFSs sequence characteristics were assessed. We used a growth-factor-induced human skin hyperplasia and a H-ras-induced mouse hyperplastic urothelium as preneoplastic models, along with an inducible U2OS-CDT1(Tet-ON) cancer cell line model, all bearing established oncogene-induced RS stimuli. Human DNA was analysed with Affymetrix SNP microarrays, while mouse DNA was analysed with Nimblegen array CGH. We studied 56 aphidicolin-type CFSs and 1914 regions of control, nonfragile DNA. Our theoretical in silico analysis spanned 2.16 billion nonoverlapping bases on human chromosomes 1-22. Our results provide direct experimental evidence indicating that genomic alterations were more common within CFSs in epidermal and urothelial preneoplastic lesions as well as in cancer. CFSs were on average less flexible than nonfragile regions, contained more guanine-cytosine (GC) and Alu sequences. Importantly, regions with loss-of-heterozygosity were also less flexible and had a higher Alu percentage.
Inflammation and Atherosclerosis Kaperonis, E.A.; Liapis, C.D.; Kakisis, J.D. ...
European journal of vascular and endovascular surgery,
04/2006, Letnik:
31, Številka:
4
Journal Article
Recenzirano
Odprti dostop
The aim of this article is to discuss the role of inflammation in atherosclerosis.
An initial chemical, mechanical or immunological insult induces endothelial dysfunction. This triggers a cascade of ...inflammatory reactions, in which monocytes, macrophages, T lymphocytes and vascular smooth muscle cells participate. Leukocyte adhesion molecules, cytokines, growth factors and metalloproteinases participate in all stages of atherogenesis. Almost all of the traditional risk factors for atherosclerosis are associated with and participate in the inflammatory process. Many infectious agents, mainly
Chlamydia pneumoniae, have been proposed as potential triggers of the cascade. The immune system has been implicated in plaque formation, through the activation of cellular and humoral immunity against innate or microbial heat shock protein 60. Methods of detection of systemic or local plaque inflammation have been developed and research is being conducted on the potential use of anti-inflammatory and antibiotic drugs in atherosclerosis.
Intercellular adhesion molecule‐1 (ICAM‐1) is a crucial receptor in the cell–cell interaction, a process central to the reaction to all forms of injury. Its expression is upregulated in response to a ...variety of inflammatory/immune mediators, including cellular stresses. The NF‐κB signalling pathway is known to be important for activation of ICAM‐1 transcription. Here we demonstrate that ICAM‐1 induction represents a new cellular response to p53 activation and that NF‐κB inhibition does not prevent the effect of p53 on ICAM‐1 expression after DNA damage. Induction of ICAM‐1 is abolished after treatment with the specific p53 inhibitor pifithrin‐α and is abrogated in p53‐deficient cell lines. Furthermore, we map two functional p53‐responsive elements to the introns of the ICAM‐1 gene, and show that they confer inducibility to p53 in a fashion similar to other p53 target genes. These results support an NF‐κB‐independent role for p53 in ICAM‐1 regulation that may link p53 to ICAM‐1 function in various physiological and pathological settings.
Replication licensing ensures once per cell cycle replication and is essential for genome stability. Overexpression of two key licensing factors, Cdc6 and Cdt1, leads to overreplication and ...chromosomal instability (CIN) in lower eukaryotes and recently in human cell lines. In this report, we analyzed hCdt1, hCdc6, and hGeminin, the hCdt1 inhibitor expression, in a series of non-small-cell lung carcinomas, and investigated for putative relations with G(1)/S phase regulators, tumor kinetics, and ploidy. This is the first study of these fundamental licensing elements in primary human lung carcinomas. We herein demonstrate elevated levels (more than fourfold) of hCdt1 and hCdc6 in 43% and 50% of neoplasms, respectively, whereas aberrant expression of hGeminin was observed in 49% of cases (underexpression, 12%; overexpression, 37%). hCdt1 expression positively correlated with hCdc6 and E2F-1 levels (P = 0.001 and P = 0.048, respectively). Supportive of the observed link between E2F-1 and hCdt1, we provide evidence that E2F-1 up-regulates the hCdt1 promoter in cultured mammalian cells. Interestingly, hGeminin overexpression was statistically related to increased hCdt1 levels (P = 0.025). Regarding the kinetic and ploidy status of hCdt1- and/or hCdc6-overexpressing tumors, p53-mutant cases exhibited significantly increased tumor growth values (Growth Index; GI) and aneuploidy/CIN compared to those bearing intact p53 (P = 0.008 for GI, P = 0.001 for CIN). The significance of these results was underscored by the fact that the latter parameters were independent of p53 within the hCdt1-hCdc6 normally expressing cases. Cumulatively, the above suggest a synergistic effect between hCdt1-hCdc6 overexpression and mutant-p53 over tumor growth and CIN in non-small-cell lung carcinomas.
Objectives: to determine the incidence of early complications following percutaneous transluminal angioplasty and to describe their management and outcome. Materials: five hundred and fifty ...consecutive patients undergoing angioplasty of 648 limbs, containing 1053 anatomical segments during a two year period were reviewed retrospectively. Results: early complications affected 109 segments (10%) in 92 limbs (14%) of 84 patients (15%). Of the 109 segments affected by early complications, 106 (97%) were managed by endovascular techniques with surgery being required on only three (3%) occasions. There were no deaths attributable to angioplasty. Conclusions: although early complications occur in 14% of limbs undergoing percutaneous transfemoral angioplasty, the majority (97%) can be managed by endovascular techniques.
Eur J Vasc Endovasc Surg 25, 125–130 (2003)
Gastrointestinal (GI) cancer constitutes a highly lethal entity among malignancies in the last decades and is still a major challenge for cancer therapeutic options. Despite the current combinational ...treatment strategies, including chemotherapy, surgery, radiotherapy, and targeted therapies, the survival rates remain notably low for patients with advanced disease. A better knowledge of the molecular mechanisms that influence tumor progression and the development of optimal therapeutic strategies for GI malignancies are urgently needed. Currently, the development and the assessment of the efficacy of immunotherapeutic agents in GI cancer are in the spotlight of several clinical trials. Thus, several new modalities and combinational treatments with other anti-neoplastic agents have been identified and evaluated for their efficiency in cancer management, including immune checkpoint inhibitors, adoptive cell transfer, chimeric antigen receptor (CAR)-T cell therapy, cancer vaccines, and/or combinations thereof. Understanding the interrelation among the tumor microenvironment, cancer progression, and immune resistance is pivotal for the optimal therapeutic management of all gastrointestinal solid tumors. This review will shed light on the recent advances and future directions of immunotherapy for malignant tumors of the GI system.
The development of cancer is a multifactorial phenomenon, while it constitutes a major global health problem. Viruses are an important factor that is involved in tumorigenesis and is associated with ...12.1% of all cancer cases. Major examples of oncogenic viruses which are closely associated with the digestive system are HBV, HCV, EBV, HPV, JCV, and CMV. EBV, HPV, JCV, and CMV directly cause oncogenesis by expressing oncogenic proteins that are encoded in their genome. In contrast, HBV and HCV are correlated indirectly with carcinogenesis by causing chronic inflammation in the infected organs. In addition, the tumor microenvironment contains various immune cells, endothelial cells, and fibroblasts, as well as several growth factors, cytokines, and other tumor-secreted molecules that play a key role in tumor growth, progression, and migration, while they are closely interrelated with the virus. The presence of T-regulatory and B-regulatory cells in the tumor microenvironment plays an important role in the anti-tumor immune reaction. The tumor immune microenvironments differ in each type of cancer and depend on viral infection. The alterations in the immune microenvironment caused by viruses are also reflected in the effectiveness of immunotherapy. The present review aims at shedding light on the association between viruses and digestive system malignancies, the characteristics of the tumor immune microenvironment that develop, and the possible treatments that can be administered.
The Androgen Receptor (AR) is emerging as an important factor in the pathogenesis of breast cancer (BC), which is the most common malignancy among females worldwide. The concordance of more than 70% ...of AR expression in primary and metastatic breast tumors implies that AR may be a new marker and a potential therapeutic target among AR-positive breast cancer patients. Biological insight into AR-positive breast cancer reveals that AR may cross-talk with several vital signaling pathways, including key molecules and receptors. AR exhibits different behavior depending on the breast cancer subtype. Preliminary clinical research using AR-targeted drugs, which have already been FDA-approved for prostate cancer (PC), has given promising results for AR-positive breast cancer patients. However, since the prognostic and predictive value of AR positivity remains uncertain, it is difficult to identify and stratify patients that would benefit from AR-targeted therapies. Herein, through a review of preclinical studies, clinical studies, and clinical trials, we summarize the biology of AR, its prognostic and predictive value, as well as its therapeutic implications by breast cancer molecular subtype.
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