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F Facchetti

Publications and source records attributed to F Facchetti.

At least 19 recordsLinked to original sources
PubMed2006

Jaw1/LRMP, a germinal centre-associated marker for the immunohistological study of B-cell lymphomas.

Jaw1, also known as lymphoid-restricted membrane protein (LRMP), is an endoplasmic reticulum-associated protein. High levels of Jaw1/LRMP mRNA have been found in germinal centre B-cells and in diffuse large B-cell lymphomas of 'germinal centre' subtype. This paper documents Jaw1/LRMP expression at the protein level in human tissues by immunohistochemical and western blotting analysis using an antibody reactive with paraffin-embedded tissues. Jaw1/LRMP was highly expressed in germinal centre B-cells (in keeping with gene expression data), in 'monocytoid B-cells', and in splenic marginal zone B-cells. It was absent, or present at only low levels, in mature T-cells, although cortical thymocytes were weakly positive. Among lymphoid neoplasms, Jaw1/LRMP was found in germinal centre-derived lymphomas (follicle centre lymphoma, Burkitt's lymphoma, lymphocyte-predominant Hodgkin's disease) but not in T-cell neoplasms (with the exception of a single T lymphoblastic lymphoma). Classical Hodgkin's disease and myeloma lacked Jaw1/LRMP but many cases of chronic lymphocytic leukaemia (but not mantle zone lymphoma) were Jaw1/LRMP-positive. Approximately half of the marginal zone lymphomas were Jaw1/LRMP-positive. In diffuse large B-cell lymphomas, Jaw1/LRMP was found in three-quarters (24/32) of the cases classified phenotypically as being of 'germinal centre' type, but it was also expressed in almost half (13/28) of the 'non-germinal centre' cases. A similar proportion of 'non-germinal centre' cases were positive for the protein products of two other genes expressed highly in germinal centre cells (HGAL/GCET2 and PAG). The fact that all three of these proteins are expressed in a significant proportion of diffuse large B-cell lymphomas assigned to the 'non-germinal centre' category indicates that the immunophenotypic categorization of diffuse large B-cell lymphoma according to cellular origin may be more complicated than currently understood. Finally, the expression of Jaw1/LRMP in other types of lymphoma and in non-lymphoid tissues/tumours may be of interest in differential diagnosis and research.

Adrenal Glands↗
PubMed2006

Cancer stem cells and therapeutic perspectives.

The cancer stem cell hypothesis suggests that neoplastic clones are maintained exclusively by a rare fraction of cells with stem cell proprieties. Stem cells are defined as cells which are able to both extensively self-renew and differentiate into progenitors. Furthermore, stem cells are also attractive candidates as origin of cancers, as in their long lifespan mutations and epigenetic changes they can increase allowing for increasing evolution toward malignancy. Herein, we discuss the evidences reported in literature on existence of cancer stem cells in several tumors and mechanisms of the extrinsic and intrinsic circuitry controlling stem cell fate as well as their possible connections to cancer. In particular, the review will focus on recent results on conserved Polycomb Group (PcG) gene family, an epigenetic chromatin modifiers involved in cancer development and also in the maintenance of embryonic and adult stem cells. There are two distinct multiprotein PcG complexes identified, Polycomb repressive complex (PRC) 1 and 2. The fact that either PRC1 Bmi1 than PRC2 SU(Z)12 components are implicated in self-renewal stem cells and up-regulated in several kind of human cancer, confirm the importance of (de)regulation of the PcG genes in cancer and stem cell biology. Moreover, Bmi1 and SU(Z)12 are downstream target of Sonic hedgehog (Shh) and Wnt signaling respectively, providing for a connection between epigenetic change regulators (PcG) and developmental-signaling pathways. Finally, potential therapies using inhibitors acting on cancer stem cell population such as cyclopamine, an inhibitor of hedgehog signalling, 6-bromoindirubin-3'-oxime (BIO) which acts on GSK3 and inhibitors of beta-catenin signaling such as exisulind and the tyrosine-kinase inhibitor STI571/Gleevac/imatinib will also discuss.

Humans↗
PubMed2006

[The Haemolymphopathology Italian Group (H.I.G.): an essential resource for the new technical and organization problems troubling modern haemolymphopathology diagnostics].

Recently, many progresses have been recorded in the molecular and histogenetic characterization of the haematopoietic and lymphoid tumours, resulting in important classifying changes. As a consequence, the exact definition of lymphoma subtype requires an integration between traditional morphologic "expertise" and several bio-functional data obtained from advanced and complex ancillary techniques (immunohistochemistry, molecular biology and cytogenetics). At the same time, the data provided by gene expression profiling studies are going to deeply modify the therapies in haematological cancers. These studies are expected to allow the achievement of single-patient-tailored genic therapy; for this reason it is necessary to get biological samples of good quality. Indeed, while these progresses contribute to highlight the pathologist's diagnostic role, they should make us reflect on the state of the art of the Italian haemolymphopathology diagnostics and on its ability to cope up with the new challanges. The aim of this article is to outline a realistic picture of the present condition, and to explain the reasons for setting up, inside SIAPEC-IAP, the Haemolymphopathology Italian Group (H.I.G.). The purpose of H.I.G. will be twofold: first of all, scheduling of a series of projects so as to the haemolymphopathological diagnostic standardization; secondly, building a national network among all the pathologists involved in this exciting and complex field of the anatomic pathology.

Europe↗
PubMed2005

Oral cavity lymphomas in immunocompetent and human immunodeficiency virus infected patients.

Oral cavity lymphoma (OCL) seems to occur more frequently in HIV-positive patients, but it is presently unknown whether HIV-related immune deficit plays a role in modifying the prevalence and the characteristics of these lymphomas. To clarify this issue, we compared OCL occurring in immunocompetent and HIV-positive patients. A comparison was made between cases of OCL occurring among 543 and 123 NHL consecutively diagnosed at a single center in immunocompetent and HIV-positive patients respectively. The prevalence of oral cavity involvement at diagnosis was significantly lower in the immunocompetent subgroup (HIV-negative: 1.66%; HIV-positive: 7.3%, P = 0.002). Extranodal T/NK nasal-nasal-type lymphoma (ET/NK-NL) was observed in 3 of 9 immunocompetent patients, whereas plasmablastic lymphoma (PBL) was observed in 3 of 9 HIV-positive patients. EBV expression correlated with HIV-positivity. Response to treatment was similar between the two subgroups, but the overall prognosis was significantly worse among HIV-positive patients. Median survival was 34 months in immunocompetent vs. 9 months in HIV-positive patients (P < 0.01). A higher frequency of oral cavity lymphoma was associated with HIV infection. ET/NK-NL and PBL seemed to be clinical entities characteristically related to immunocompetent and HIV-positive subgroups, respectively. Chemotherapy was feasible and effective in both subgroups, although a poor prognosis was associated with immunodeficiency.

Acquired Immunodeficiency Syndrome↗
PubMed2004

Modulation of pro- and anti-apoptotic factors in human melanoma cells exposed to histone deacetylase inhibitors.

Valproic acid (VPA, 2-propylpentanoic acid) is an established drug in the long-term therapy of epilepsy. Recently, VPA was demonstrated to inhibit histone deacetylases (HDACs) class I enzyme at therapeutically relevant concentrations, thereby, mimicking the prototypical histone deacetylase inhibitors, tricostatin A (TSA) or suberoylanilide hydroxamic acid (SAHA). In the present study, we investigated the cellular effects of VPA, TSA and SAHA on four human melanoma cell lines (WM115, WM266, A375, SK-Mel28) with particular reference to the modulation of regulators of apoptosis, including Bcl-2, BclXL, Mcl-1, Apaf-1, BclXs, NOXA, TRAIL-R1, TRAIL-R2, caspase 8, and survivin). Firstly, we found that VPA induced apoptosis in two of the four human melanoma cell lines, while both TSA and SAHA exhibited an antiproliferative and apoptotic effects in all four cell lines, a different expression of Bcl-2 and BclX(L/S) occurred. On the other hand, SAHA and VPA modulated differently pro- and anti-apoptotic factors. In particular, the treatment with VPA enhanced the level of expression of survivin only in VPA-resistant cell lines, whereas down-regulation of survivin was induced by VPA and SAHA in VPA-sensitive cells. In the latter, since activation of caspase 8 was documented, a receptor-mediated apoptosis was suggested. Taken together, our results suggest that HDAC inhibitors may represent a promising therapeutic strategy to treat melanoma.

Apoptosis↗
PubMed2003

Photosensitive erythema multiforme and erythema multiforme-like polymorphous light eruption.

BACKGROUND: Photosensitive erythema multiforme (EM) is a rare disorder. It usually occurs only if a herpes virus infection or ingestion of drugs precedes exposure to sunlight in selected patients. METHODS: We report a 37-year-old man who had recurrent EM eruptions following sun exposures over a period of 20 years. Lesions were prevalently located on exposed skin, but unexposed skin and mucosa of the oropharynx were also affected. The patient had poor tolerance to sunlight and denied having herpes simplex infection or using drugs. RESULTS: Provocative phototest induced clinically and histologically similar lesions at low dose thresholds of UVA (10 J/cm2) and UVB (100 mJ/cm2). CONCLUSION: On the basis of clinical and histological findings and results of phototesting, a diagnosis of photosensitive EM was made. The EM-like variant of polymorphous light eruption is discussed in the differential diagnosis.

Adult↗
PubMed2002

[Plasmacytoid monocytes and plasmacytoid dendritic cells. Immune system cells linking innate and acquired immunity].

Plasmacytoid monocytes (PM), originally described by pathologists as cells occurring in the interfollicular area of human lymph nodes, are emerging cells in the scenario of the immune system. PM normally circulate between peripheral blood, lymphoid organs and sites of inflammation using specific migratory pathways and signalling; PM are easily recognizable on the basis of their distinctive morphology and phenotype (CD3-, CD11c-, CD14-, CD20-, CD36+, CD56-, CD68+, CD123+, BD-CA2+). Recently it has been shown that PM produce high levels of type I interferon, thus corresponding to natural interferon-producing cells. Furthermore, PM or their precursors may differentiate in vitro towards a new subset of dendritic cells, supporting a function in antigen-dependent T cell priming. Taken together, these data suggest PM play a relevant role in the immune system, linking innate and acquired immunities. In fact, PM seem to be crucial in the pathogenesis of different immune-mediated human diseases including viral infections and autoimmune disorders, and to be involved in the immune control of some malignant neoplasms. The issue concerning the cell lineage of PM remains unresolved, but the frequent association between a tumoral expansion of PM and myelo-monocytic leukemia, together with cytogenetic identity between the two cell populations identified in rare cases, corroborates the myeloid origin of PM.

Animals↗
PubMed2002

[LAT (linker for activation of T cells): a useful marker for megakaryocyte evaluation on bone marrow biopsies].

Detection of atypical megakaryocytes in bone marrow biopsies, especially in cases of myelodysplastic syndromes (MDS), chronic myeloproliferative disorders (CMPD) and acute leukemias, is facilitated by staining for markers such as Ulex europaeus agglutinin (UEA)-J, CD31, CD61 and von Willebrand factor (VWF), the latter being considered the most sensitive. Recently, LAT (linker for activation of T cells), a molecule involved in T-cell activation and platelet aggregation, was found to be expressed by megakaryocytes and platelets in tissue sections. We compared VWF and LAT immunoreactivity on megakaryocytes in 64 bone marrow biopsies from 12 normal controls (NC), and from patients with MDS (n=18), CMPD (n=21) and acute megakaryocytic leukemia (AML-M7, n=13). Immunostaining was performed on paraffin sections with polyclonal antibodies against VWF and LAT. Immunoreactivity was evaluated by counting positive megakaryocytes in 10 high-power fields, and values were compared using Student's t test for paired data. Both VWF and LAT predominantly stained the cytoplasm of megakaryocytes, although LAT was also recognizable on the cell membrane. In most biopsies, the immunoreactivity of the two antibodies was quite similar. No significant differences were noticed between the mean values of VWF+ and LAT+ megakaryocytes. However, in 22 cases (5 NC; 5 MDS; 6 CMPD; 6 AML-M7), the number of LAT+ megakaryocytes was at least 30% higher than VWF+cells, while in 3 cases opposite findings were found. In 3 AML-M7 cases, anti-LAT antibodies stained numerous megakaryocytes, but anti-VWF staining was practically negative; in another 5 AML-M7 cases, anti-LAT labeling was much stronger than anti-VWF staining. LAT represents a useful immunohistochemical marker for megakaryocytes in normal and pathological conditions. It seems to be expressed by megakaryocytes more than VWF in most cases and, particularly, in conditions associated with poorly differentiated megakaryocytes, such as acute megakaryocytic leukemias. The use of LAT staining should be recommended in association with other megakaryocyte markers in the study of bone marrow biopsies in cases of hematopoietic disorders.

Adaptor Proteins, Signal Transducing↗
PubMed2001

BDCA-2, a novel plasmacytoid dendritic cell-specific type II C-type lectin, mediates antigen capture and is a potent inhibitor of interferon alpha/beta induction.

Plasmacytoid dendritic cells are present in lymphoid and nonlymphoid tissue and contribute substantially to both innate and adaptive immunity. Recently, we have described several monoclonal antibodies that recognize a plasmacytoid dendritic cell-specific antigen, which we have termed BDCA-2. Molecular cloning of BDCA-2 revealed that BDCA-2 is a novel type II C-type lectin, which shows 50.7% sequence identity at the amino acid level to its putative murine ortholog, the murine dendritic cell-associated C-type lectin 2. Anti-BDCA-2 monoclonal antibodies are rapidly internalized and efficiently presented to T cells, indicating that BDCA-2 could play a role in ligand internalization and presentation. Furthermore, ligation of BDCA-2 potently suppresses induction of interferon alpha/beta production in plasmacytoid dendritic cells, presumably by a mechanism dependent on calcium mobilization and protein-tyrosine phosphorylation by src-family protein-tyrosine kinases. Inasmuch as production of interferon alpha/beta by plasmacytoid dendritic cells is considered to be a major pathophysiological factor in systemic lupus erythematosus, triggering of BDCA-2 should be evaluated as therapeutic strategy for blocking production of interferon alpha/beta in systemic lupus erythematosus patients.

Amino Acid Sequence↗
PubMed2001

Hodgkin disease developing in patients infected by human immunodeficiency virus results in clinical features and a prognosis similar to those in patients with human immunodeficiency virus-related non-Hodgkin lymphoma.

BACKGROUND: Unlike aggressive non-Hodgkin lymphoma (NHL), Hodgkin disease (HD) develops rarely in patients who are infected by human immunodeficiency virus (HIV), and its characteristics are not well defined. The authors analyzed the clinicopathologic and prognostic features from a consecutive series of patients with HIV-associated HD who were observed at their institution and compared them with the features observed in a concurrent series of patients with systemic HIV-related NHL. METHODS: Eighteen patients with HIV infection who were diagnosed and treated uniformly from 1985 to 1999 at a single primary referral center were analyzed. Their demographic, immunologic, and clinicopathologic features; responses to treatment; and outcomes were compared with those of 98 patients with systemic NHL of aggressive histology who were diagnosed during the same period and with 165 HIV negative patients with HD. RESULTS: HIV-associated HD and NHL occurred in patients with similar age, gender, HIV risk factors, degree of immunodeficiency, and incidence of previous acquired immunodeficiency syndrome. The clinical presentation of HIV-associated HD was atypical and was more aggressive than in HIV negative patients (mediastinal involvement, 11%; Stage III-IV, 84%; B symptoms, 83%). It was similar to HIV-related NHL, except for the frequency of extralymph node disease, which was seen less frequently in patients who had HD (56%) compared with patients who had NHL (82%; P = 0.025), and the frequency of bone marrow involvement, which was unexpectedly higher in patients who had HD (50%) compared with patients who had NHL (20%; P = 0.011). Potentially curative treatment was administered to 77% of patients with HD and 66% of patients with NHL. Complete remission and disease recurrence rates as well as disease free and overall survival rates did not differ significantly, with estimated overall survival at 5 years of 24% in patients with HD and 23% in patients with NHL. CONCLUSIONS: HIV-associated HD is an aggressive disease with demographic, clinical, and prognostic features nearly identical to those of HIV-related NHL.

AIDS-Related Opportunistic Infections↗
PubMed2001

TREM-1 amplifies inflammation and is a crucial mediator of septic shock.

Host innate responses to bacterial infections are primarily mediated by neutrophils and monocytes/macrophages. These cells express pattern recognition receptors (PRRs) that bind conserved molecular structures shared by groups of microorganisms. Stimulation of PRR signalling pathways initiates secretion of proinflammatory mediators, which promote the elimination of infectious agents and the induction of tissue repair. Excessive inflammation owing to bacterial infections can lead to tissue damage and septic shock. Here we show that inflammatory responses to microbial products are amplified by a pathway mediated by triggering receptor expressed on myeloid cells (TREM)-1. TREM-1 is an activating receptor expressed at high levels on neutrophils and monocytes that infiltrate human tissues infected with bacteria. Furthermore, it is upregulated on peritoneal neutrophils of patients with microbial sepsis and mice with experimental lipopolysaccaride (LPS)-induced shock. Notably, blockade of TREM-1 protects mice against LPS-induced shock, as well as microbial sepsis caused by live Escherichia coli or caecal ligation and puncture. These results demonstrate a critical function of TREM-1 in acute inflammatory responses to bacteria and implicate TREM-1 as a potential therapeutic target for septic shock.

Animals↗
PubMed2001

Monocytes from Wiskott-Aldrich patients differentiate in functional mature dendritic cells with a defect in CD83 expression.

Wiskott-Aldrich syndrome (WAS) is an X-linked disorder characterized by congenital thrombocytopenia and progressive deterioration of the immune function. Dendritic cells (DC) are key effectors in the induction of specific immunity and are highly specialized in antigen uptake and subsequent migration to draining lymph nodes. DC were generated in vitro from circulating monocytes from ten WAS patients characterized by a different disease score. Immature DC showed similar morphology and membrane phenotype, as compared to normal DC. In chemotaxis assay, immature DC had a reduced migration in response to MIP-1alpha/CCL3, but efficiently endocytosed the macromolecules FITC-dextran and FITC-albumin. Upon terminal differentiation with LPS or CD40 ligand, the acquisition of a mature surface phenotype was variably achieved among WAS patients, with increased expression of CD80, CD86 and DC-LAMP. In contrast, the expression of CD83 was usually low. A defective up-regulation of CD83 was also observed in the lymph node from one WAS patient, whose DC stained positively for DC-LAMP. Mature DC from all the patients tested, but one, significantly migrated in vitro in response to MIP-3beta, a finding confirmed in vivo by the detection of HLA-DR/DC LAMP-positive cells in secondary lymphoid organs. When tested in MLR assays, both immature and mature WAS DC induced allogenic T cell proliferation in a manner comparable to control DC. Collectively these results suggest that, although many functional activities of WAS DC are essentially similar to normal DC, subtle and selective alterations of DC differentiation were also observed, with reduced migratory activity of immature DC and defective CD83 expression upon maturation.

Antigen-Presenting Cells↗
PubMed2001

Myeloperoxidase expression by histiocytes in Kikuchi's and Kikuchi-like lymphadenopathy.

Forty-five examples of Kikuchi's lymphadenitis (KL), 5 Kikuchi-like lupus erythematosus lymphadenopathies, 25 nonnecrotizing lymphadenitidies (5 toxoplasmic, 5 sarcoid-like, 6 dermatopathic, 4 suppurative, 3 tubercular, 2 with sinus histiocytosis), 4 examples of hyaline-vascular Castleman disease (CD), 2 plasmacytoid monocyte tumors (PM-Ts), and 61 accessory cell neoplasms were studied by a panel of antibodies, including the PG-M1 (against a macrophage-restricted CD68 epitope) and a polyclonal anti-myeloperoxidase (MPO). In KL and Kikuchi-like lupus erythematosus lymphadenopathies, 25 to 75% of CD68(+) histiocytes co-expressed MPO. This did not occur in nonnecrotizing lymphadenitidies and accessory cell neoplasms. MPO(+)/CD68(+) elements corresponded to nonphagocytosing mononuclear cells and some crescentic macrophages and phagocytosing histiocytes. Typical PMs were MPO(-)/CD68(+) in all cases, including CD and PM-T. Our observations suggest that in KL and KL-like lymphadenopathies: 1) MPO(+)/CD68(+) blood monocytes might be attracted into tissues because of the lack or paucity of granulocytes and the need of MPO for oxidative processes; 2) PMs are more likely to be involved in the cytotoxic immune reaction than in phagocytic phenomena; 3) the peculiar phenotype of the histiocytic component can be usefully used for the differentiation from malignant lymphoma and PM-T.

Adolescent↗
PubMed2001

Mutations in the thrombomodulin and endothelial protein C receptor genes in women with late fetal loss.

Late fetal loss can be associated with placental insufficiency and coagulation defects. Thrombomodulin (TM) and the endothelial protein C receptor (EPCR) are glycoprotein receptors expressed mainly on the endothelial surface of blood vessels and also in the placenta; they both play a key physiological role in the protein C anticoagulant pathway. Defects in these proteins might play an important role in the pathogenesis of late fetal loss. We performed a case-control study in 95 women with unexplained late fetal loss (> 20 weeks), to elucidate whether TM or EPCR gene mutations were associated with an increased risk for this complication of pregnancy. The control group comprised 236 women who gave birth to at least one healthy baby and had no history of late fetal death or obstetrical complications. The entire TM and EPCR genes, including the promoter region, were screened. In total, five mutations were identified in the TM gene in 95 patients and three in 236 control subjects, and two mutations were identified in the EPCR gene in 95 patients and one in 236 control subjects. The relative risk for late fetal loss when having a mutation in the TM or EPCR gene was estimated by an odds ratio of 4.0 (95% CI 1.1-14.9). In conclusion, identified mutations in the TM and EPCR genes of women with unexplained fetal loss are more prevalent compared with women with no obstetrical complications.

Abortion, Habitual↗