1,721,401 research outputs found
Telomere/telomerase interplay in virus-driven and virus-independent lymphomagenesis: pathogenic and clinical implications
No full textTelomerase is a ribonucleoprotein complex critically involved in extending and maintaining telomeres. Unlike the majority of somatic cells, in which hTERT and telomerase activity are generally silent, normal lymphocytes show transient physiological hTERT expression and telomerase activity according to their differentiation/activation status. During lymphomagenesis, induction of persistent telomerase expression and activity may occur before or after telomere shortening, as a consequence of the different mechanisms through which transforming factors/agents may activate telomerase. Available data indicate that the timing of telomerase activation may allow the distinction of two different lymphomagenetic models: (i) an early activation of telomerase via exogenous regulators of hTERT, along with an increased lymphocyte growth and a subsequent selection of cells with increased transforming potential may characterize several virus-related lymphoid malignancies; (ii) a progressive shortening of telomeres, leading to genetic instability which favors a subsequent activation of telomerase via endogenous regulators may occur in most virus-unrelated lymphoid tumors. These models may have clinically relevant implications, particularly for the tailoring of therapeutic strategies targeting telomerase
Infectious etiopathogenesis of extranodal lymphomas
No full textSeveral infectious agents are established causes of non-Hodgkin’s lymphoma in humans. They include human immunodeficiency virus (HIV), Epstein-Barr virus (EBV), human herpes virus 8 (HHV-8), hepatitis C virus (HCV), and Helicobacter pylori. In addition, a causal role is suspected for hepatitis B virus (HBV), Borrelia burgdorferi, Campylobacter jejuni, and various Chlamydia species. For some of these agents, notably HIV, HHV-8, H. pylori, Chlamydia, and B. burgdorferi, the association seems specific to one or a few types of extra - nodal lymphomas, while EBV is associated with a variety of nodal and extranodal lymphomas. In the case of HCV, the risk of both nodal and extranodal lymphomas seems increased among chronically infected individuals. No data are available on HBV and risk of extranodal lymphoma. In the following sections, the epidemiological and pathogenetic evidence linking infectious agents to extra - nodal lymphoma is reviewed. Infectious agents may contribute to lymphomagenesis by two main pathogenetic mechanisms. First, a direct role is played mainly by viruses such as EBV and HHV-8, which infect target cells and express a variety of viral products that promote cell growth and survival. Additional environmental and genetic factors contribute to the malignant phenotype. The virus genome is usually present in all tumor cells. Secondly, infectious agents, mainly bacteria, may indirectly contribute to lymphomagenesis by providing a chronic antigenic stimulus that would drive the development of extranodal lymphomas along a continuum pathway, starting from the development of acquired mucosaassociated lymphoid tissue (MALT), through low-grade lymphoma, and ultimately leading to high-grade tumors. Proliferation of B cells may be dependent on the contact with infiltrating antigen-specific CD4+ helper T cells. Antigens derived from the infectious agent may be cross-reactive with self-antigens, which, in turn, may further sustain B cell growth. This model indicates that infectious agents could trigger autoimmune reactivity and emphasizes the likely relevant role of autoimmune mechanisms in the pathogenesis of some extranodal lymphomas (Figure 4.1). © 2008 by Taylor & Francis Group, LLC
Association Between B-Type Epstein-Barr-Virus and Hodgkins-Disease in Immunocompromised Patients
No full text
GSK-3 beta inhibition - At the crossroad between Akt and mTOR constitutive activation to enhance cyclin D1 protein stability in mantle cell lymphoma
No full textStrategies able to downregulate the aberrant expression of cyclin D1 may prove of therapeutic relevance in cancer patients. This is particularly true for mantle cell lymphoma (MCL) in which cyclin D1 is overexpressed as a consequence of the t(11;14)(q13;q32) translocation. We have recently demonstrated that an increased cyclin D1 stability also contributes to the high levels of this protein observed in MCL cells. This effect is mediated by a constitutive activation of PI3-K/Akt, which keeps GSK-3β inhibited. Here we show that inhibition of PI3-K/Akt induces a 40% decrease of cyclin D1 half-life as a result of accumulation of the dephosphorylated/active form of GSK-3β within the nucleus, where this kinase can phosphorylate cyclin D1 on Thr286 thereby promoting its nuclear export. Translocation of cyclin D1 into the cytoplasm is mediated by the nuclear exportin CRM1, whose association with cyclin D1 increases following PI3-K/Akt inhibition. Notably, rapamycin downregulated GSK-3β Ser9 phosphorylation with concurrent nuclear export of cyclin D1 only in MCL cells in which GSK-3β is under the control of mTOR. These findings suggest that the ability to downregulate cyclin D1 through GSK-3β may identify subsets of MCL patients who may benefit from the treatment with mTOR inhibitors and stimulate further studies to assess whether the inability to affect GSK-3β activity may constitute a clinically relevant resistance factor to mTOR inhibitors. ©2008 Landes Bioscience
Chlamydial infection: the link with ocular adnexal lymphomas
No full textChlamydiae are obligate intracellular bacteria that grow in eukaryotic cells and cause a wide spectrum of diseases. They can establish persistent infections, are mitogenic in vitro, promote polyclonal cell proliferation in vivo and induce resistance to apoptosis in infected cells-properties that might contribute to tumorigenesis. In fact, Chlamydophila psittaci (Cp) has been linked to the development and maintenance of ocular adnexal marginal zone B-cell lymphoma (OAMZL). In this indolent malignancy, Cp is transported by monocytes and macrophages and causes both local and systemic infection. Cp elementary bodies are viable and infectious in the conjunctiva and peripheral blood of patients with OAMZL. Bacterial eradication with antibiotic therapy is often followed by lymphoma regression. Despite recent advances in the understanding of this bacterium-lymphoma association, several questions remain unanswered. For instance, prevalence variations among different geographical areas and related diagnostic and therapeutic implications remain a major investigational issue. We will focus on clinical and therapeutic implications of chlamydial infections in patients with lymphomas and summarize the current knowledge on the association between Cp infection and OAMZL. Available data on the epidemiology, biology and pathogenesis of this association are analyzed and new investigative and clinical approaches are discussed
3° Incontro scientifico Virus e Tumori Solidid. Ferrara 23 Marzo 2012.
No full textL’ iniziativa desidera in prima istanza verificare
lo stato dell’arte nel settore della oncologia
virale con specifico riferimento a virus
potenzialmente oncogeni trovati associati a
tumori solidi umani. In due precedenti incontri,
con il congresso di Pavia “Virus e Tumori Solidi”
del 20-21 Ottobre 2011, e con il meeting di
Aviano (PN) del 19 Gennaio 2011 sono state
poste le basi culturali per affrontare in maniera
multidisciplinare un argomento di forte attualità
ed impatto nel panorama sia scientifico che
sanitario.
Il terzo incontro che si svolge oggi a Ferrara, 23
Marzo 2012, ha come finalità un’ulteriore
disamina del tema e la proposizione di specifici
argomenti che potranno diventare progetti di
ricerca da presentare alle Agenzie finanziatrici
sia pubbliche che private. Il gruppo di ricercatori
del settore sono in grado di affrontare sia gli
argomenti di base, relativi ai processi biologici,
che le applicazioni cliniche, tipiche delle fasi di
diagnosi e cura dei tumori solidi. Inoltre, durante
il meeting scientifico si metteranno a confronto
diversi know-how relativi a tecnologie,
metodiche e protocolli standardizzati sia per il
laboratorio di ricerca che per la pratica clinica
con l’intento di condividere qualità e
riproducibilità dei dati
Infectious agents in mucosa-associated lymphoid tissue-type lymphomas: Pathogenic role and therapeutic perspectives
No full textMucosa-associated lymphoid tissue (MALT) lymphoma probably constitutes the best in vivo model showing how complex interplay between B lymphocytes and the surrounding microenvironment may lead to a neoplastic disorder. After the seminal discovery of the pathogenic association between Helicobacter pylori and gastric MALT lymphomas, evidence suggests the possible involvement of other infectious agents in the development of MALT lymphomas arising at different body sites. Although several other bacteria (Borrelia burgdorferi, Campylobacter jejuni, and Chlamydia psittaci) and viruses (Hepatitis C virus) seem to play a role in lymphomas presenting at different locations, a possible common pathogenic mechanism is emerging. Several lines of evidence suggest that different infectious agents might provide a chronic antigenic stimulation that elicits host immune responses able to promote clonal B-cell expansion. This model is also substantiated by the increasing number of patients with MALT lymphomas who exhibit objective clinical responses after antimicrobial therapy. A multidisciplinary approach is critical to better understand the complex etiopathogenesis of MALT lymphomas with the final goal to dissect the clinicopathologic heterogeneity of these disorders and design more tailored preventive and therapeutic approaches
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