Biomedical subjects

Antonio Cozzio

Publications and source records attributed to Antonio Cozzio.

15 recordsLinked to original sources

PubMed2006

Intra-lesional low-dose interferon alpha2a therapy for primary cutaneous marginal zone B-cell lymphoma.

Primary cutaneous marginal zone lymphomas (pcMZL) belong to the primary cutaneous B-cell lymphoma (pCBCL) group. They are characterized by their restriction to the skin and a high likelihood of recurrence after various treatment modalities. First-line therapy consists of surgery and radiotherapy. These therapies may not always be indicated in young patients or in patients with pCBCL located in the face, where surgery or radiotherapy may leave disfiguring scars or radioderma. Eight patients with pcMZL were treated with intra-lesional injections of 3 million units of recombinant IFNalpha2a three times per week. The patients either did not want to undergo or did not qualify for surgical excision or radiotherapy due to inappropriate localization or age. All patients experienced complete tumor regression after a mean of 8.5 weeks (range 3 - 20). Two patients relapsed 4 and 12 months after treatment, respectively, but tumor regression was repeated after additional cycles of intra-lesional IFNalpha2a. All other patients remained free of disease. Thus, intra-lesional IFNalpha2a may represent a valuable alternative to surgery and radiotherapy as first-line treatment of pcMZL.

Adult↗

PubMed2006

Standard and experimental therapy in cutaneous T-cell lymphomas.

Cutaneous T-cell lymphomas are a heterogeneous group of lymphoproliferative disorders, characterized by the accumulation of clonal lymphocytes in the skin. Skin-directed therapies are the preferred first-line modalities. There are interesting new developments in topical therapy using retinoids and gene-therapy products such as adenovirus- interferon (IFN)-gamma. Systemic treatment uses biologicals such as fusion molecules, monoclonal antibodies and immune response modifiers (IFNs and retinoids), and well-tolerated antiproliferative drugs such as methotrexate. Evidence-based treatment recommendation exists but is hampered by the lack of large multicenter randomized trials.

Humans↗

PubMed2006

Pathogenesis and therapy of cutaneous lymphomas--progress or impasse?

The cutaneous environment hosts a number of hematopoietic neoplasms that are dominated by primary cutaneous (PC) T-cell lymphomas. Recent progress in molecular biology and immunology has provided tools to investigate the pathogenesis and the biology of these neoplasms. This review highlights newest findings concerning the immune biology of CD4+ CD56+ hematodermic neoplasms, and PC T-cell and B-cell lymphomas, speculating how these can be translated into more sophisticated, biology-based treatment approaches in the near future.

CD4 Antigens↗

PubMed2006

[Perspective of cutaneous lymphoma reserach].

Primary cutaneous lymphomas are characterized by an expansion of hematopoietic cells in the special microenvironment of the skin. They represent a special challenge both for researches and for clinicians who treat patients with these disorders. New research data concerning the biology of lymphocytes and the cutaneous microenvironment have increased our knowledge of these diseases in the last decades. The new WHO/EORTC classification definitely will facilitate a more detailed investigation of the various subtypes.

Biomedical Research↗

PubMed2006

Cutaneous malignant lymphomas: update 2006.

Cutaneous lymphomas represent a unique group of lymphomas and are the second most frequent extranodal lymphomas. As with other neoplasias, the pathogenesis is based mainly on a stepwise accumulation of mutations of suppressor genes and oncogenes caused by genetic, environmental or infectious factors. The diagnostic work-up includes clinical, histological, imaging and hematological investigations and in many cases immunohistochemical and molecular biological analyses. The current WHO/EORTC classification of cutaneous lymphomas differentiates "mature T-cell and NK-cell lymphomas", "mature B-cell lymphomas" and "immature hematopoietic malignancies", their variants and subgroups. It is compatible with the WHO classification for neoplasias of the hematopoietic and lymphoid tissue and respects the organ-specific peculiarities of primary cutaneous lymphomas. The assignment of the various types of cutaneous lymphomas into prognostic categories (pre-lymphomatous "abortive" disorders; definite malignant lymphomas of low-grade malignancy; definite malignant lymphomas of high-grade malignancy) provides essential information on the biological behavior and allows an appropriate planning of the therapeutic strategy, which may be topical or systemic and aggressive or non-aggressive. Besides the classical options for therapy, there are new and "experimental" strategies, the efficacy of which has to be studied in clinical trials.

Dermatology↗

PubMed2005

CD4+CD56+ hematodermic neoplasms bear a plasmacytoid dendritic cell phenotype.

CD4+CD56+ hematodermic neoplasms (HNs) with initial presentation in the skin are characterized by highly aggressive behavior and poor prognosis. Recent studies indicate that malignant cells, which are devoid of common T-, B-, NK-, and myeloid lineage markers, may be of plasmacytoid dendritic cell (pDC) origin. We undertook a study to assess the expression of several pDC-associated molecules on a series of 5 CD4+CD56+ HN cases. CD123 was expressed in all 5 cases, with some heterogeneity in individual cases. All but one case revealed fine membranous BDCA-2 staining of the dermal infiltrate. pDC-like phenotype of the malignant infiltrating cells was confirmed by costaining of BDCA-2+ cells with CD123 and CD4. MxA protein, representing the surrogate marker for lesional type I interferon activity, was expressed in 4 of 5 evaluated cases. Our findings further substantiate the putative pDC origin of CD4+CD56+ HNs.

Adult↗

PubMed2005

WHO/EORTC classification of cutaneous lymphomas 2005: histological and molecular aspects.

UNLABELLED: The new WHO/EORTC classification for cutaneous lymphomas comprises mature T-cell and natural killer (NK)-cell neoplasms, mature B-cell neoplasms, and immature hematopoietic malignancies. It reflects the unique features of lymphoproliferative diseases of the skin, and at the same time it is as compatible as possible with the concepts underlying the WHO classification for nodal lymphomas and the EORTC classification of cutaneous lymphomas. This article reviews the histological, phenotypical, and molecular genetic features of the various nosological entities included in this new classification. These findings always have to be interpreted in the context of the clinical features and biologic behavior. AIM: To review the histological, phenotypical and molecular genetic features of the various nosological entities of the new WHO/EORTC classification for cutaneous lymphomas. METHODS: Extensive review of the literature cited in Medline and own data of the authors. RESULTS: The WHO/EORTC classification of cutaneous lymphomas comprises mature T-cell and NK-cell neoplasms, mature B-cell neoplasms and immature hematopoietic malignancies. It reflects the unique features of primary cutaneous lymphoproliferative diseases. CONCLUSION: This classification is as much as possible compatible with the concept of the WHO classification for nodal lymphomas and the EORTC classification of cutaneous lymphomas. The histological, phenotypical and molecular genetic features always have to be interpreted in the context of the clinical features and biologic behavior.

Europe↗

PubMed2004

Varicella-zoster virus infection of human neural cells in vivo.

Varicella-zoster virus (VZV) establishes latency in sensory ganglia and causes herpes zoster upon reactivation. These investigations in a nonobese diabetic severe combined immunodeficient mouse-human neural cell model showed that VZV infected both neurons and glial cells and spread efficiently from cell to cell in vivo. Neural cell morphology and protein synthesis were preserved, in contrast to destruction of epithelial cells by VZV. Expression of VZV genes in neural cells was characterized by nuclear retention of the major viral transactivating protein and a block in synthesis of the predominant envelope glycoprotein. The attenuated VZV vaccine strain retained infectivity for neurons and glial cells in vivo. VZV gene expression in differentiated human neural cells in vivo differs from neural infection by herpes simplex virus, which is characterized by latency-associated transcripts, and from lytic VZV replication in skin. The chimeric nonobese diabetic severe combined immunodeficient mouse model may be useful for investigating other neurotropic human viruses.

Animals↗

PubMed2004

Psoriasis triggered by toll-like receptor 7 agonist imiquimod in the presence of dermal plasmacytoid dendritic cell precursors.

BACKGROUND: It has been proposed that the innate immune system plays a central role in driving the autoimmune T-cell cascade leading to psoriasis; however, there is no direct evidence for this. OBSERVATIONS: We observed aggravation and spreading of a psoriatic plaque when treated topically with the toll-like receptor (TLR) 7 agonist imiquimod. The exacerbation of psoriasis was accompanied by a massive induction of lesional type I interferon activity, detected by MxA expression after imiquimod therapy. Since imiquimod induces large amounts of type I interferon production from TLR7-expressing plasmacytoid dendritic cell precursors (PDCs), the natural interferon-producing cells of the peripheral blood, we asked whether PDCs are present in psoriatic skin. We identified high numbers of PDCs in psoriatic skin lesions (up to 16% of the total dermal infiltrate) based on their coexpression of BDCA2 and CD123. By contrast, PDCs were present at very low levels in atopic dermatitis and not detected in normal human skin. CONCLUSIONS: This study shows that psoriasis can be driven by the innate immune system through TLR ligation. Furthermore, our finding that large numbers of PDCs infiltrate psoriatic skin suggests a role of lesional PDCs as type I interferon-producing targets for the TLR7 agonist imiquimod.

Administration, Topical↗

PubMed2004

Febrile ulceronecrotic Mucha-Habermann disease with clonality: a cutaneous T-cell lymphoma entity?

Febrile ulceronecrotic Mucha-Habermann disease (FUMHD) is a severe variant of pityriasis lichenoides et varioliformis acuta (PLEVA). PLEVA patients only very rarely have systemic signs; the cutaneous lesions are usually asymptomatic, but may be pruritic and may heal with scarring. FUMHD often starts out as classic PLEVA, but goes on to develop widespread ulceronecrotic lesions and is associated with a high mortality rate. Whether Pityriasis lichenoides chronica (PLC) and PLEVA form a spectrum rather than single entities of clonal lymphoproliferative diseases has been discussed. Recently, it has been proposed that FUMHD, too, is a clonal lymphoproliferative disorder. Here, we report two cases of FUMHD with monoclonal T-cell population, as detected by Southern blot analysis. We propose that clonal FUMHD represents a cutaneous T-cell lymphoma entity.

Adult↗

PubMed2004

Microbial colonization and atopic dermatitis.

PURPOSE OF REVIEW: Atopic dermatitis is a chronic relapsing, pruritic inflammation of the skin, affecting 10-20% of children and 1-3% adults worldwide, with increasing prevalence in highly industrialized countries. Here we review relevant studies, published since June 2002, about immunological triggers in atopic dermatitis, with emphasis on the role of microbial colonization. RECENT FINDINGS: During the past 2 years there has been considerable interest in the mechanisms and trigger factors underlying the increased microbial colonization of atopic skin. Staphylococcus aureus appears to play a significant role as it leads to a worsening of disease severity by producing superantigens that induce a strong proliferation of T cells and favour a T helper type 2-like cytokine profile. In addition, different Malassezia species seem to elicit and maintain skin inflammation after sensitization, but the precise immunological pathway has not yet been described. All these microorganisms are not only perceived as aetiological factors but also as agents responsible either for sustained disease activity or resistance to therapy by modulation of the immune response. SUMMARY: New insights into the important role of microorganisms and their key immunomodulatory pathways in atopic dermatitis may have important implications from a therapeutic point of view because patients with atopic dermatitis may benefit from more than just anti-inflammatory treatment in the future.

Adolescent↗

PubMed2003

Similar MLL-associated leukemias arising from self-renewing stem cells and short-lived myeloid progenitors.

We have used the hematopoietic system as a model to investigate whether acute myeloid leukemia arises exclusively from self-renewing stem cells or also from short-lived myeloid progenitors. When transduced with a leukemogenic MLL fusion gene, prospectively isolated stem cells and myeloid progenitor populations with granulocyte/macrophage differentiation potential are efficiently immortalized in vitro and result in the rapid onset of acute myeloid leukemia with similar latencies following transplantation in vivo. Regardless of initiating cell, leukemias displayed immunophenotypes and gene expression profiles characteristic of maturation arrest at an identical late stage of myelomonocytic differentiation, putatively a monopotent monocytic progenitor stage. Our findings unequivocally establish the ability of transient repopulating progenitors to initiate myeloid leukemias in response to an MLL oncogene, and support the existence of cancer stem cells that do not necessarily overlap with multipotent stem cells of the tissue of origin.

Acute Disease↗

PubMed2003

Flt3 ligand regulates dendritic cell development from Flt3+ lymphoid and myeloid-committed progenitors to Flt3+ dendritic cells in vivo.

Stimulation of Flt3 receptor tyrosine kinase through its cognate ligand expands early hematopoietic progenitor and dendritic cells (DCs) in humans and mice. The exact developmental stages at which hematopoietic progenitors express Flt3, are responsive to its ligand, and subsequently develop to DCs, are not known. Here we show that common lymphoid and common myeloid progenitors, as well as steady state DCs in thymus, spleen, and epidermis, express Flt3. The receptor is down-regulated once definitive B cell, T cell, and megakaryocyte/erythrocyte commitment occurs, and Flt3 is not detectable on other steady state hematopoietic cell populations. Upon in vivo Flt3 ligand (Flt3L) administration, Flt3+ progenitor cells and their progeny DCs are expanded, whereas Flt3- downstream progenitors are not, or are only slightly increased. Transplantation of common lymphoid and common myeloid progenitors and subsequent Flt3L injection increases progeny DCs of both precursor populations. These findings provide a definitive map of Flt3 expression in the hematopoietic hierarchy and directly demonstrate that Flt3L can drive DC development along both the lymphoid and myeloid developmental pathways from Flt3+ progenitors to Flt3+ DCs.

Animals↗

PubMed2003

Expression of truncated PrP targeted to Purkinje cells of PrP knockout mice causes Purkinje cell death and ataxia.

PrP knockout mice with disruption of only the PrP-encoding region (Zürich I-type) remain healthy, whereas mice with deletions extending upstream of the PrP-encoding exon (Nagasaki-type) suffer Purkinje cell loss and ataxia, associated with ectopic expression of Doppel in brain, particularly in Purkinje cells. The phenotype is abrogated by co-expression of full-length PrP. Doppel is 25% similar to PrP, has the same globular fold, but lacks the flexible N-terminal tail. We now show that in Zürich I-type PrP-null mice, expression of N-terminally truncated PrP targeted to Purkinje cells also leads to Purkinje cell loss and ataxia, which are reversed by PrP. Doppel and truncated PrP probably cause Purkinje cell degeneration by the same mechanism.

Alleles↗

PubMed2003

MLL-GAS7 transforms multipotent hematopoietic progenitors and induces mixed lineage leukemias in mice.

A specific association with mixed lineage leukemias suggests that MLL oncoproteins may selectively target early multipotent hematopoietic progenitors or stem cells. We demonstrate here that a representative MLL fusion protein, MLL-GAS7, impairs the differentiation and enhances the in vitro growth of murine hematopoietic cells with multipotent features. The multilineage differentiation potential of these cells was suggested by their immuno-phenotypes and transcriptional programs and confirmed by their ability to induce three pathologically distinct leukemias in mice, including an acute biphenotypic leukemia (ABL) that recapitulates the distinctive hallmark features of many MLL-associated leukemias in humans. This experimental modeling of ABL in mice highlights its origin from multipotential progenitors that arrest at a bipotential stage specifically targeted or induced by MLL oncogenes.

Animals↗