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Results, questions, perspectives of a study on human polyomavirus BK and molecular actors in prostate cancer development
Full text linkBackground: Prostate cancer (PC) is a common tumor in Western countries. Several risk factors play significant roles. MYC, BIRC5/survivin, CDC25 and P53 may contribute to PC risk. As demonstrated, human Polyomavirus BK (BKV) could affect cellular homeostasis contributing to PC pathogenesis. Materials and Methods: Biological samples were collected from PC patients. Viral
RNA was searched using quantitative polymerase chain reaction (PCR), whereas a qualitative PCR was employed to find particular viral sequences. Proper size amplicons were analyzed. Single nucleotide polymorphisms (SNPs) were detected in p53 coding regions by means of a specific PCR.
C-MYC, BIRC5/survivin and CDC25 gene expression was investigated using a Retro Transcriptional Quantitative PCR. Results: Viral DNA copy number was higher in cancer tissues taken from Gleason score 9 patients with Gleason score 7. Different p53 mutated compared to patients exons
were found according to tumor advanced stage and a statistical significant correlation was found between Gleason score and p53 mutational rate. C-MYC, BIRC5/survivin and CDC25 expression was de-regulated according to the literature. Conclusion: The presence of BKV and its variants in transformed cells does not exclude viral pressure in cell immortalization. Expression of other target genes evidenced a significant change in their regulation, useful for cancer drug discovery and therapies
A molecular analysis of the human polyomaviruses DNA sequences in prostate cancer patients reveals a high frequency of JCV detection: preliminary results
No full textBiological agents therapy in crohn's disease
No full textCrohn's disease (CD) is a chronic inflammatory bowel disease (IBD) with significant morbidity and health care costs. The disease seems to occur when the intestinal immune cascade is triggered by microbial antigens in genetically susceptible individuals. Over-activation of the enteric immune and inflammatory pathways causes mucosal damage resulting in the clinical signs and symptoms. Various medications, including 5-aminosalicylates, antibiotics, corticosteroids, and immune-modulators have traditionally been used to control inflammation. Their use is intended to prevent surgery and improve the patient's quality of life, but none cure the disease. Unfortunately, many patients require steroids to control their symptoms and a wide range of dose-related adverse effects makes this an unappealing strategy. Immune-modulators are effective maintenance drugs, but have a slow onset of action with clinical remission rates of approximately 40%. Recently, biological therapy has brought a paradigm shift in the management of CD and other autoimmune diseases, such as rheumatoid arthritis, psoriatic arthritis and multiple sclerosis (MS), resulting in marked decrease of disability and improvement in quality of life. Biologic therapies encompass agents with diverse modes of action, including the tumor necrosis factor a (TNFa) inhibitors, such as infliximab and adalimumab, that are the monoclonal antibody-based therapy of choice in CD. Natalizumab, an adhesion molecule inhibitor, is also used in refractory CD. Although the remarkable efficacy of biological therapy has resulted in significant success in CD management, serious side effects do occur, necessitating careful monitoring of therapy. In addition to other well documented neurologic, hematologic, immunologic, cardiovascular and malignant adverse effects, biological agents therapy has been associated with the development of serious life-threatening infections. In particular, the human polyomavirus JC (JCV) reactivation in CD after biological therapy and its association with progressive multifocal leukoencephalopathy (PML) has been found in one patient treated with natalizumab. After this case of PML and other two cases in MS patients, commercial and investigational use of natalizumab was suspended in February 2005 but was subsequently resumed for MS and for CD, only through a special restricted distribution program to patients who had refractory disease and who have failed both immune-suppressants and anti-TNFa agents and who have careful screening and subsequent monitoring for JCV infection. Therefore, this chapter will address an immunological overview of CD physiopathology, followed by the focusing on the use of infliximab, adalimumab and natalizumab in CD, and on their side effects, with particular attention to the issue of JCV reactivation. © 2013 Nova Science Publishers, Inc. All rights reserved
High frequency of JCV DNA detection in prostate cancer tissues
Full text linkBACKGROUND: Prostate cancer (PC) represents the most frequently diagnosed cancer in men. Exposure to infectious agents has been considered to induce prostatic inflammation and cancerous transformation. Controversial data exist concerning the role of the human polyomaviruses BK (BKV) and JC (JCV) in PC etiology. Therefore, a possible association between these polyomaviruses and PC was investigated.
MATERIALS AND METHODS: Urine, blood and fresh prostatic tissue specimens were collected from 26 patients with PC. The presence of BKV and JCV, the possible non-coding control region (NCCR) variations and the genotyping analysis of viral protein 1 (VP1) of both viruses were assessed.
RESULTS: Data showed a preferential viral re-activation in the urinary compartment and a statistically significant prevalence of JC viruria and of BKV in PC tissues. A BKV DDP-like NCCR sequence was isolated in two patients, whereas JCV NCCR was consistently of an archetypal structural organization. A prevalence of the European genotypes was observed for both viruses.
CONCLUSION: Our data demonstrated the presence of JCV DNA in 14/24 (58.3%) cancerous prostatic tissue specimens, confirming the results obtained in a previous study, in which JCV has been defined as common inhabitant of the prostate, and opening the discussion about its potential role in PC
Human polyomavirus JC reactivation and pathogenetic mechanisms of progressive multifocal leukoencephalopathy and cancer in the era of monoclonal antibody therapies
No full textProgressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system caused by the neurotropic human polyomavirus JC (JCV) lytic infection of oligodendrocytes. PML was first described as a complication of lymphoproliferative disorders more than 50 years ago and emerged as a major complication of human immunodeficiency virus (HIV) infection in the 1980s. Despite the ubiquity of this virus, PML is rare and always seen in association with underlying immunosuppressive condition, such as HIV infection, autoimmune diseases, cancer, and organ transplantation. JCV remains quiescent in the kidneys, where it displays a stable archetypal non-coding control region (NCCR). Conversely, rearranged JCV NCCR, including tandem repeat patterns found in the brain of PML patients, have been associated with neurovirulence. The specific site and mechanism of JCV NCCR transformation is unknown. According to one model, during the course of immunosuppression, JCV departs from its latent state and after entering the brain, productively infects and destroys oligodendrocytes. Although the majority of PML cases occur in severely immunesuppressed individuals, PML has been increasingly diagnosed in patients treated with biological therapies such as monoclonal antibodies (mAbs) that modulate immune system functions: in fact, CD4(+) and CD8(+) T lymphopenia, resulting from this immunomodulatory therapy, are the primary risk factor. Furthermore, JCV reactivation in nonpermissive cells after treatment with mAbs, such as intestinal epithelial cells in Crohn's disease patients, in association with other host tumor-inducing factors, could provide valid information on the role of JCV in several malignancies, such as colorectal cancer
Reactivation of human polyomavirus JC in patients affected by psoriasis vulgaris and psoriatic arthritis and treated with biological drugs: Preliminary results
No full textPsoriasis vulgaris (PsV) and psoriatic arthritis (PSA) are inter-related heritable inflammatory skin diseases. Psoriatic lesions develop as a result of abnormal immune responses, hyperproliferation and altered differentiation of keratinocytes, and a notable subset of psoriatic patients develops PsA, characterized by joints inflammation. Recently, biological drugs were introduced to treat these diseases. However, this therapy has already been associated with the development of serious life-threatening infections, such as the reactivation of human polyomavirus JC (JCV), responsible for the progressive multifocal leukoencephalopathy (PML), a lethal demyelinating disease caused by oligodendrocytes lytic infection. Therefore, the aims of our study were the investigation of the possible JCV reactivation in PsV and PsA patients treated with adalimumab, etanercept, and methotrexate, performing quantitative real-time PCR in sera and skin biopsies at the time of recruitment (T0) and after 3 (T3) and 6 (T6) months of treatment, and the sequencing analysis of the JCV non-coding control region (NCCR). We found JCV DNA in 5/15 PsV patients and in 2/15 PsA patients and JCV NCCR sequence analysis always showed a structure similar to non-pathogenic CY archetype, with random occurrence of a few irrelevant point mutations. Nevertheless the poor number of patients analyzed, our preliminary data can pave the way for taking into account that the follow-up of JCV DNA detection and the JCV NCCR sequence analysis in psoriatic patients may be important to evaluate the risk of PML onset, considering that patients affected by autoimmune diseases and treated with biologics continue to rise. J. Cell. Physiol. 227: 37963802, 2012. (c) 2012 Wiley Periodicals, Inc
MALDI-TOF MS VS VITEK2: comparison of systems for the identification of microorganisms responsible of bacteremia.
No full textWe evaluated the reliability and accuracy of the combined use of MALDI-TOF MS and classical ID VITEK2 to identify monomicrobial infection in blood culture bottles. In total, 70 consecutive positive blood cultures were included in this study. Positive blood culture bottles were subjected to Gram staining and subcultured on solid media. Isolates grown from such culture media were used for classical ID using VITEK2 system. In parallel, an aliquot was subjected to a lysing-centrifugation method and used for the identification with the MALDI-TOF system. Results evidenced the correct genus and species identification of 91.4 % of microorganisms responsible for bacteremia with an agreement to the species and the genus level. If compared with the standard method VITEK2, our simple and cost-effective sample preparation method would be very useful for rapid identification of microorganisms using blood culture bottles. In fact, the direct method showed rapid and reliable results, especially for the gram-negative group
New Insights on Human Polyomavirus JC and Pathogenesis of Progressive Multifocal Leukoencephalopathy
Full text linkJohn Cunningham virus (JCV) is a member of the Polyomaviridae family. It was first isolated from the brain of a patient with Hodgkin disease in 1971, and since then the etiological agent of the progressive multifocal leukoencephalopathy (PML) was considered. Until the human immunodeficiency virus (HIV) pandemic, PML was rare: in fact HIV-induced immunodeficiency is the most common predisposing factor accounting for 85% of all instances of PML. This data led to intense research on JCV infection and resulted in better understanding of epidemiology and clinic-pathologic spectrum. Recently, cases of PML have been observed after the introduction of monoclonal antibodies, such as natalizumab, rituximab, efalizumab, and infliximab, in the treatment of autoimmune disease, underlining the important role of host immunity in PML pathogenesis. In this review current understanding of the JCV infection and the new findings relating to the pathogenesis of PML has been comprehensively revised, focusing our attention on the interaction between the cellular and viral molecular pathways implicated in the JCV infection and the modulating role of host immune surveillance in the viral reactivation from a latent state
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