Natural killer (NK) cells are an important component of the innate immune response against microbial infections and tumors. Direct involvement of NK cells in tumor growth and infiltration has not yet been demonstrated clearly. Primary effusion lymphoma (PEL) cells were able to produce tumors and asc …

Primary effusion lymphoma (PEL) is a rare B-cell neoplasm, associated with Kaposi sarcoma-associated herpes virus/human herpes virus-8 (KSHV/HHV-8), arising as malignant effusions in body cavities. PEL cells do not harbor conventional genetic cancer mutations; however, their oncogenesis is mainly attributed to HHV-8 latent genes. Treatment strategies are inefficient resulting in poor prognosis of PEL patients, stressing the need for new effective therapy. ST1926 is a synthetic retinoid with favorable antitumor properties and no cross-resistance with the natural retinoid, all-trans retinoic acid. ST1926 has shown potent apoptotic activities on a variety of solid tumors and hematologic malignancies in in vitro and in vivo models. In the present study we elucidated the antitumor activities and underlying molecular mechanism of ST1926 using in vitro, ex vivo, and in vivo PEL preclinical models. ST1926, at sub‑micromolar concentrations, displayed potent antiproliferative effects on PEL cell lines ...

Kaposis sarcoma-associated herpesvirus (KSHV), also called human herpesvirus 8 (HHV-8), is a B-cell-tropic human herpesvirus (reviewed in Refs. 1 , 2 ). The virus was first discovered in 1994 in Kaposis sarcoma (KS) tumors of AIDS patients. In AIDS patients, KSHV is also associated with two lymphoproliferative disorders, namely, primary effusion lymphoma [PEL; initially called body cavity based lymphoma (BCBL); Ref. 3] and multicentric Castlemans disease (4) . To date, multiple KSHV isolates have been sequenced and been shown to contain a 120-kb central long unique region encoding ∼80 putative open reading frames (5, 6, 7) . Antibodies against KSHV exist in virtually all of the HIV-infected as well as in HIV-uninfected KS patients. Prospective longitudinal studies found that increases in peripheral-blood viral load as well as KSHV-specific antibody titers precede the onset of disease and correlate with increased risk for KS. These observations argue that KSHV is required for disease ...

We report on an HIV-1 infected patient who was diagnosed with primary effusion lymphoma (PEL) and who achieved a long-term remission after treatment with only highly active antiviral therapy (HAART).. In September 2005, a 42-year-old white homosexual man was referred to our clinic because he tested positive for HIV. He had a persistent low-grade fever, dry cough, asthenia and occasional dyspnoea, while his chest X-ray showed a left pleural effusion, unresponsive to empiric antibiotic treatment. Thoracentesis showed 350 ml of clear fluid with 1070 cells/ml (lymphocytes), 5.9 g/dl of proteins, 66 mg/ml of glucose, 4.667 and 307 U/l of lactate dehydrogenase (normal plasma value ,460 U/l) in pleural effusion and plasma, respectively. Cytological and immunophenotipical analysis of pleural fluid showed large pleiomorphic cells CD45+, CD138+, CD3− and CD19−, respectively. PCR for human herpes virus 8 (HHV-8) DNA tested positive for both cells and plasma. A bone marrow biopsy was found normal. A ...

Fingerprint Dive into the research topics of Characterization of immunologic and virological parameters in HIV-infected patients with primary effusion lymphoma during antiblastic therapy and highly active antiretroviral therapy. Together they form a unique fingerprint. ...

The cells were established from pleural effusion from a human immunodeficiency virus (HIV) negative patient diagnosed with primary effusion (body cavity based) lymphoma (PEL). BC-3 is a primary effusion lymphoma cell line originated in 1995 by Leandros Arvanitakis and Ethel Cesarman.

HHV-8, also designated Kaposis sarcoma-associated herpesvirus is associated with multicentric Castlemans disease and primary effusion lymphoma, a rare type of non-Hodgkin lymphoma affecting the body cavities. HHV-8 K14 is expressed at the surfaces of infected cells solely during the lytic cycle. It interacts with human CD200R, a receptor expressed on myeloid cells that is involved in locally restricting macrophage activation. The interaction of HHV-8 K14 with CD200R allows the protein to locally restrain macrophage activation by inhibiting TNFα production. HHV-8 encodes a viral-cyclin that is homologous to cellular D-type cyclins, a class of positive cell cycle mediators that are physiologically regulated by the p27 cell cycle inhibitor. HHV-8 cyclin is not sensitive to p27, however, which may explain the coexistence of p27 and high proliferative index of HHV-8 observed in individuals with primary effusion lymphoma (PEL).. Clone: ...

Figure 1. Left panel: morphologic and immunohistochemical analyses. (A, B). The mediastinal mass biopsy obtained from patient 1006 displayed a diffuse infiltration with large PEL-like tumor cells containing irregularly shaped nuclei and abundant cytoplasm. (A. Hematoxylin and Eosin (HE) stain, x400); latency-associated nuclear antigen-1 (LANA-1) immunostaining showed that most tumor cells exhibited the pattern of nuclear speckles characteristic of HHV-8-infected cells. B. LANA-1, x400). C, D. The spleen of patient 977 was infiltrated with coalescent sheets of plasmablasts. These cells had a moderate amphophilic cytoplasm and a large rounded nucleus often peripherally located and containing one or more prominent nucleoli (C, HE stain, x400); they were HHV-8-infected. (D. LANA-1, x400). Right panel: HHV-8 clonality analysis. Southern blot hybridization of Taq-I-digested genomic DNA with a 32P-labeled HHV-8 terminal repeat probe (803 bp NotI fragment, kindly provided by Y. Chang, Columbia ...

Human herpesvirus 8 (HHV-8) is associated with endothelial Kaposis sarcoma (KS) and B cell malignancies primary effusion lymphoma and multicentric Castlemans...

Primary effusion lymphoma (PEL) is a rare subtype of large B-cell lymphoma representing approximately 4% of all immunodeficiency syndrome (AIDS)-related lymphomas. It occurs in two forms; classic and extracavitary/solid. PEL classically presents as a lymphomatous effusion in the pleural, pericardial, or peritoneal cavities, but may also manifest as extracavitary masses involving the gastrointestinal tract, lungs, skin and central nervous system. PEL is universally associated with the human herpesvirus 8 (HHV8) and most often occurs in the setting of immunodeficiency. Additionally tumor cells often show coinfection with Epstein-Barr Virus (EBV).. The tumor cells show morphologic variability which ranges from immunoblastic/plasmablastic to anaplastic. The nuclei are large and round to more irregular or lobated with prominent nucleoli. On histological sections these cells may appear more uniform and monotonous than on cytologic specimens. Immunophenotypically the lymphoma cells usually express ...

Primary effusion lymphoma (PEL) is a largely incurable malignancy of B cell origin with plasmacytic differentiation. Here, we report the identification of a highly effective inhibitor of PEL. This compound, 6-ethylthioinosine (6-ETI), is a nucleoside analog with toxicity to PEL in vitro and in vivo, but not to other lymphoma cell lines tested. We developed and performed resistome analysis, an unbiased approach based on RNA sequencing of resistant subclones, to discover the molecular mechanisms of sensitivity. We found different adenosine kinase-inactivating (ADK-inactivating) alterations in all resistant clones and determined that ADK is required to phosphorylate and activate 6-ETI. Further, we observed that 6-ETI induces ATP depletion and cell death accompanied by S phase arrest and DNA damage only in ADK-expressing cells. Immunohistochemistry for ADK served as a biomarker approach to identify 6-ETI-sensitive tumors, which we documented for other lymphoid malignancies with plasmacytic features. ...

Primary Effusion Lymphoma (PEL) is a very unusual effusion. It is characterized by its ability to cause fluid to accumulate in the lungs and/or belly. Most of the lymphoma, which AIDS patients get,...

B-cell lymphoid tumors that occur in association with AIDS. Patients often present with an advanced stage of disease and highly malignant subtypes including BURKITT LYMPHOMA; IMMUNOBLASTIC LARGE-CELL LYMPHOMA; PRIMARY EFFUSION LYMPHOMA; and DIFFUSE, LARGE B-CELL, LYMPHOMA. The tumors are often disseminated in unusual extranodal sites and chromosomal abnormalities are frequently present. It is likely that polyclonal B-cell lymphoproliferation in AIDS is a complex result of EBV infection, HIV antigenic stimulation, and T-cell-dependent HIV activation ...

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Both AIDS-KS libraries were found to express HHV8 RNA. The detection of relatively low tag counts for HHV8 specific ORFs can be explained by only a low percentage of cells expressing HHV8 RNA. The viral T1.1 and T0.7 transcripts are the predominant viral transcripts found in AIDS-KS tumours [19] and in primary effusion lymphoma (PEL) [33], another disease associated with HHV8. Recently, the global HHV8 genome expression of two PEL cell lines was studied using viral micro-arrays [34, 35]. A good correlation between the kinetic behaviour of viral genes in cultured PEL cells and the transcription patterns observed in AIDS-KS biopsies has been observed [36]. The pattern of gene expression concurred with the functional roles of the viral genes. Transcripts corresponding to ORF K4.2, 18 and 59 were simultaneously expressed in induced PEL cells and were all classified as secondary lytic genes. We detected in our SAGE libraries only tags belonging to the five HHV8 ORFs mentioned before, suggesting ...

Science & Technology, Life Sciences & Biomedicine, Biochemistry & Molecular Biology, IRES, eIF4E, viruses, RNA structure, translation, CAP-INDEPENDENT TRANSLATION, RIBOSOME ENTRY SITE, HEPATITIS-C VIRUS, RNA SECONDARY STRUCTURE, MULTICENTRIC CASTLEMANS-DISEASE, SMALL-MOLECULE INHIBITION, PRIMARY EFFUSION LYMPHOMA, OPEN READING FRAME, GAG CODING REGION, KAPPA-B PATHWAY ...

Herpes Virus Type 8 / HHV8, 0.1 ml. Kaposis sarcoma-associated herpesvirus (KSHV) belongs to the gamma-(2)-herpesvirus subfamily and has been closely linked to the Kaposis sarcoma, primary effusion lymphoma (PEL) and multicentric Castlemans

Kaposis sarcoma-associated herpesvirus (KSHV) bears four genes with homology to human being interferon regulatory factors (IRFs). PEL cell lines resulted in improved MHC II levels; overexpression of vIRF-3 in KSHV-negative B cells prospects to downmodulation of MHC II. This rules could be traced back to inhibition of class II transactivator (CIITA) transcription by vIRF-3. Reporter assays exposed the gamma interferon (IFN-γ)-sensitive CIITA promoters PIV and PIII were inhibited by vIRF-3. Consistently IFN-γ levels improved upon vIRF-3 knockdown in PEL cells. IFN-γ rules by vIRF-3 was confirmed in reporter assays as well as by upregulation of standard IFN-γ target genes upon knockdown of vIRF-3 in PEL cells. In summary we conclude that vIRF-3 contributes to the viral immunoevasion by downregulation of IFN-γ and CIITA and thus MHC II manifestation. Intro Kaposis sarcoma-associated herpesvirus (KSHV) also termed human being herpesvirus 8 (HHV-8) belongs to the gammaherpesvirus-2 subgroup ...

This report presents the clinical, cytological and molecular features of a pleural effusion lymphoma which developed in a patient treated for chronic myeloid leukaemia after five years of dasatinib therapy. This effusion lymphoma recurred three times but largely resolved after pleurocentesis and steroid treatment. More reports on such unusual cases may improve our understanding and management of patients with this rare adverse effect associated with dasatinib ...

Pels, E; Groot, J W.; Mullink, R; Unnik, J A.; Otter, D W.; and Exudate, F O., Cells with ring-shaped nuclei. (1980). Subject Strain Bibliography 1980. 3014 ...

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Background Kaposi sarcoma-associated herpesvirus (KSHV) is the etiologic agent of primary effusion lymphomas (PEL). Herpesvirus Type 8 (HHV-8)) [1], is linked to all forms of Kaposi sarcoma, primary effusion lymphoma (PEL) [2C4], and some forms of multicentric Castelmans disease (MCD) [5,6]. PEL is a monoclonal/oligoclonal, rare, aggressive and body cavity-based B-cell lymphoma, accounting for approximately 3% of AIDS-related lymphomas [7,8]. This unusual lymphoproliferative disorder is divided into classical and solid variants. The classical PEL is characterized by malignant effusions in the serosal surfaces, mostly pleural, pericardial and peritoneal cavities and by the absence of an obvious tumor mass, lymphadenopathy or hepatosplenomegaly [9]. The solid PEL manifests with extracavitary tissue-based tumors that may precede PEL development [10], may follow malignant effusions [11], or may not at all be associated with PEL serous effusions [3,6,10,12C14]. The presence of KSHV genome in PEL ...

TY - JOUR. T1 - Low-grade Epstein-Barr virus positive plasma cell proliferations of precursor plasma cell origin. T2 - Report of two cases. AU - Oaxaca, Gabriel G.. AU - Coffey, Amy M. AU - Gannon, Francis H.. AU - Szigeti, Reka. PY - 2017/7/30. Y1 - 2017/7/30. N2 - B cell lymphoproliferative disorders with plasmacytic differentiation are a spectrum of neoplasms arising from B cells in different stages of maturation, which include marginal zone lymphoma, plasmablastic lymphoma, ALK-positive diffuse large B cell lymphoma, primary effusion lymphoma, and plasma cell neoplasms. Within this group, Epstein-Barr virus (EBV) is mostly linked to plasmablastic lymphoma and primary effusion lymphoma. EBV has only rarely been associated with the remaining entities and occurs almost exclusively in immunocompromised patients. We report two cases of EBV positive, mature appearing plasma cell proliferations without previously identified immunodeficiency. The proliferating plasma cells showed co-expression of ...

To determine the presence of Kaposi sarcoma-associated herpesvirus (KSHV) and other serologic markers, we tested serum specimens of 339 Amerindians, 181 rural non-Amerindians, and 1,133 urban blood donors (13 Amerindians) in the Brazilian Amazon. High KSHV seroprevalence in children and inverse association with herpes simplex virus type 2 indicates predominant nonsexual transmission among Amerindians.

Our laboratory investigates Kaposis sarcoma-associated herpesvirus (KSHV) or human herpesvirus 8 (HHV-8). KSHV has a causative role in Kaposis sarcoma, primary effusion lymphomas and multicentric Castlemans disease, an aggressive lymphoproliferative disorder. KSHV latently infects tumor cells and has evolved an intricate mechanism to efficiently persist in proliferating cells in the absence of chromosomal integration. KSHV persists in latently infected cells as an extrachromosomal, multiple copy plasmid (episome), from which it expresses several viral genes including the latency-associated nuclear antigen (LANA). LANA is essential for KSHV episome persistence in cells. LANA mediates viral DNA replication, which occurs in concert with cell DNA replication, and then tethers KSHV episomes to mitotic chromosomes to ensure their efficient segregation to progeny nuclei, thereby avoiding loss of the genome in the cytoplasm. LANA also exerts effects on cell growth and transcription. We are currently ...

Author Summary Heat shock proteins, such as Hsp90, aid the folding of proteins. They seem to be essential to sustain the growth of cancer cells. Hsp90 inhibitors are in clinical trials for many cancers but with mixed results, presumably since these proteins have many clients. The mechanism for drug efficacy and tumor-type variation in responses is not understood. Here we show that in the case of Kaposi sarcoma and primary effusion lymphoma, which are cancers caused by Kaposi sarcoma associated herpesvirus (KSHV/HHV8) an essential viral protein, LANA, binds to Hsp90 and is a client of Hsp90. Different small molecule Hsp90 inhibitors reduce the expression of LANA. At the same time they reduce the expression of the newly discovered co-receptor of KSHV ephA2, of Akt, cdc2 and ephrin-B2. Since LANA is required to maintain the virus latent in all tumor cells, a process, which is periodically aided by de novo infection, these inhibitors interfere with essential components of viral pathogenesis and in vivo

We have shown here that cultured primary human DMVEC cultures can be infected at different efficiencies by KSHV virions derived from several PEL cell lines. The infection causes a phenotype involving aligned and swirling bunches of elongated spindle-shaped cells that closely resembles that displayed by the pathogenic spindle cells of nodular KS lesions. Importantly, KSHV infection of the DMVEC cultures and the associated spindle cell conversion phenotype correlate almost completely with constitutive LANA1 protein expression in the same cells. Recent studies by Dupin et al. (10) have also confirmed that almost all spindle cells in late nodular KS lesions express LANA1. The similarity to the latent state found in both PEL cell lines and KS lesions is emphasized by the punctate nuclear character of the LANA1 signal (4), implying that the viral genomes also establish a multicopy episomal state in infected spindloid DMVEC. However, although the KSHV-infected spindle cells have high mitotic indices ...

Holda Anagho 14 is a doctoral student in infection biology at Hannover Medical School in Germany, where she studies interactions between Hepatitis Delta Virus (HDV) and host cells in the lab of Professor Thomas von Hahn, M.D. At Amherst, she majored in biology, where she first became excited about research after a summer internship in Professor Caroline Gouttes lab. While at Amherst, she also took several German language courses and served as president of the German theme house. After graduation, she spent a year as a research fellow at the National Cancer Institute in Bethesda, where she conducted research on the effects of immunomodulatory drugs in primary effusion lymphoma, caused by Kaposis sarcoma-associated herpesvirus (KSHV) in the lab of Dr. Robert Yarchoan 71, M.D. There she first became interested in viruses. With generous support from Amherst College through the Kellogg Fellowship, she enrolled in the masters program in molecular biosciences at the University of Heidelberg in ...

Holda Anagho 14 is a doctoral student in infection biology at Hannover Medical School in Germany, where she studies interactions between Hepatitis Delta Virus (HDV) and host cells in the lab of Professor Thomas von Hahn, M.D. At Amherst, she majored in biology, where she first became excited about research after a summer internship in Professor Caroline Gouttes lab. While at Amherst, she also took several German language courses and served as president of the German theme house. After graduation, she spent a year as a research fellow at the National Cancer Institute in Bethesda, where she conducted research on the effects of immunomodulatory drugs in primary effusion lymphoma, caused by Kaposis sarcoma-associated herpesvirus (KSHV) in the lab of Dr. Robert Yarchoan 71, M.D. There she first became interested in viruses. With generous support from Amherst College through the Kellogg Fellowship, she enrolled in the masters program in molecular biosciences at the University of Heidelberg in ...

The AIDS-defining malignancies are Kaposi's sarcoma, aggressive B-cell lymphoma, primary CNS lymphoma and cervix carcinoma. Non-AIDS-defining malignancies like Hodgkin's lymphoma and anal carcinoma occur more frequently in the HIV-positive population but are not necessarily related to the level of immune suppression. Kaposi's sarcoma is a vascular tumour caused by human herpesvirus 8 and occurs mainly in the skin and mucous membranes but can involve any organ. Management of Kaposi's sarcoma starts with HAART and, if clinically indicated, either local therapy like radiotherapy or systemic chemotherapy. AIDS-related lymphomas present at an advanced stage, are usually associated with B-symptoms and extranodal disease, and often involve unusual sites. The commonest histologies are diffuse large B-cell and Burkitts's lymphoma. Those seen almost exclusively in HIV are plasmablastic and primary effusion lymphoma. Primary CNS lymphoma in HIV is associated with a CD4 count < 50,

Castleman disease causes growths to form on your lymph nodes. Take these questions with you to your next doctors appointment to learn more about it.

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TY - JOUR. T1 - Targeted inhibition of calcineurin signaling blocks calcium-dependent reactivation of Kaposi sarcoma-associated herpesvirus. AU - Zoeteweij, J. P.. AU - Moses, A. V.. AU - Rinderknecht, A. S.. AU - Davis, D. A.. AU - Overwijk, W. W.. AU - Yarchoan, R.. AU - Orenstein, J. M.. AU - Blauvelt, A.. PY - 2001/4/15. Y1 - 2001/4/15. N2 - Kaposi sarcoma-associated herpesvirus (KSHV) is associated with KS, primary effusion lymphoma (PEL), and multicentric Castleman disease. Reactivation of KSHV in latently infected cells and subsequent plasma viremia occur before the development of KS. Intracellular signaling pathways involved in KSHV reactivation were studied. In latently infected PEL cells (BCBL-1), KSHV reactivation in single cells was determined by quantitative flow cytometry. Viral particle production was determined by electron microscope analyses and detection of minor capsid protein in culture supernatants. Agents that mobilized intracellular calcium (ionomycin, thapsigargin) ...

Background:. - KSHV-associated multicentric Castleman disease (KSHV-MCD) is caused by a herpes virus known as KSHV. This disease can also cause several other cancers, including Kaposi sarcoma. People with KSHV-MCD often have symptoms like fever, weight and muscle loss, and fluid in the legs or abdomen. Tocilizumab may be able to block the chemicals in the body that cause KSHV-MCD symptoms. Researchers want to test this drug and other anti-virus drugs to find the best combination of drugs to treat KSHV-MCD.. Objectives:. - To test the effectiveness of tocilizumab with and without other anti-virus drugs for KSHV-MCD.. Eligibility:. - People at least 18 years of age who have KSHV-MCD and have certain symptoms and blood abnormalities caused by their KSHV-MCD.. Design:. ...

Background:. - KSHV-associated multicentric Castleman disease (KSHV-MCD) is caused by a herpes virus known as KSHV. This disease can also cause several other cancers, including Kaposi sarcoma. People with KSHV-MCD often have symptoms like fever, weight and muscle loss, and fluid in the legs or abdomen. Tocilizumab may be able to block the chemicals in the body that cause KSHV-MCD symptoms. Researchers want to test this drug and other anti-virus drugs to find the best combination of drugs to treat KSHV-MCD.. Objectives:. - To test the effectiveness of tocilizumab with and without other anti-virus drugs for KSHV-MCD.. Eligibility:. - People at least 18 years of age who have KSHV-MCD and have certain symptoms and blood abnormalities caused by their KSHV-MCD.. Design:. ...

While the aetiology of idiopathic multicentric Castleman disease (iMCD) remains unclear, the involvement of autoinflammatory mechanisms has been suggested. Herein we report a Japanese patient with iMCD with a novel heterozygous Ile729Met mutation in exon 10 of the Mediterranean fever (MEFV) gene.We performed genetic analysis via targeted next-generation sequencing analysis and Sanger sequencing and conducted molecular dynamics simulations to investigate the hydrophobic interactions around the 729th amino acid in human pyrin.In February 2011, a 59-year-old man was diagnosed with IgG4-related disease at our department based on the findings of cervical and hilar lymphadenopathies, typical lung lesions and cervical lymph node biopsy. The patient was followed up without treatment, as he was asymptomatic. However, he had been experiencing prolonged fatigue and fever with high levels of CRP since June 2017. Axillary lymph node biopsy findings led to the diagnosis of iMCD. He was successfully treated ...

Dr. Uldricks major research interests are the natural history and management of virally associated malignancies that occur in the setting of HIV/AIDS and other immune disorders. Therapeutic studies focus on novel approaches to the treatment of several viral-associated malignancies using approaches that incorporate cytokine and growth factor manupulation and targeting of reservoirs of gamma-herpesvirus infected lymphoid cells using monoclonal antobodies or virus-activated cytotoxic therapy.. Active projects include: (1) Evaluation of the natural history of KSHV-associated disorders, including Kaposi sarcoma, KSHV-associated multicentric Castleman disease, primary effusion lymphoma, and a novel entity we described, KSHV-associated Inflammatory Cytokine Syndrome (KICS) (2) Early-phase treatment studies in KSHV-associated malignancies employing immune modulating, anti-angiogenic and virus-activated cytotoxic therapies (3) Evaluation of radiation-sparing approaches for HIV-associated primary CNS ...

Kaposis sarcoma-associated herpesvirus (KSHV; also referred to as human herpesvirus 8 [HHV-8]) belongs to the gammaherpesvirus family, which includes Epstein-Barr virus (EBV), herpesvirus saimiri (HSV), and murine gammaherpesvirus 68 (MHV-68) (1). KSHV infection is associated with Kaposis sarcoma (KS), the most common cancer in HIV-infected patients (1). KSHV is also linked to the development of several other lymphoproliferative malignancies, including primary effusion lymphoma (PEL) and a subset of multicentric Castlemans disease (2). Similar to other herpesviruses, the life cycle of KSHV consists of latent and lytic replication phases (3). Following acute infection, KSHV establishes latency in the immunocompetent hosts, where KSHV maintains its genome as an episome and expresses only a limited number of viral proteins or viral mRNAs. Thus, KSHV latency is an effective strategy for evading host immune detection (3). In KS lesions, most of the tumor cells are latently infected by KSHV, ...

Kaposi sarcoma herpesvirus (KSHV) is specifically associated with Kaposi sarcoma (KS) and 2 B cell lymphoproliferative diseases, namely primary effusion lymphoma (PEL) and multicentric Castleman disease (MCD). KS, PEL, and MCD are largely incurable and poorly understood diseases most common in HIV-infected individuals. Here, we have revealed the role of viral FLICE-inhibitory protein (vFLIP) in the initiation of PEL and MCD by specifically expressing vFLIP at different stages of B cell differentiation in vivo. Mice showed MCD-like abnormalities and immunological defects including lack of germinal centers (GCs), impaired Ig class switching, and affinity maturation. In addition, they showed increased numbers of cells expressing cytoplasmic IgM-λ, a thus far enigmatic feature of the KSHV-infected cells in MCD. B cell-derived tumors arose at high incidence and displayed Ig gene rearrangement with downregulated expression of B cell-associated antigens, which are features of PEL. Interestingly, these ...

Kaposis sarcoma-associated herpesvirus (KSHV), or human herpesvirus 8 (HHV8) is a gammaherpesvirus and the etiological agent of Kaposis sarcoma, primary effusion lymphoma and multicentric Castleman disease. The KSHV genome contains genes for a unique group of proteins with homology to cellular interferon regulatory factors, termed viral interferon regulatory factors (vIRFs). This review will give an overview over the oncogenic, antiapoptotic and immunomodulatory characteristics of KSHV and related vIRFs.. ...

Kaposis sarcoma-associated herpesvirus (KSHV) is a newly-identified human herpesvirus and an emerging pathogen. Increasing evidence indicate that this virus is the etiologic agent of Kaposis sarcoma (KS), primary effusion lymphoma (PEL) and multicentric Castlemans disease (MCD), leading neoplasia of AIDS patients. Unique among all DNA tumor viruses, KSHV lytic replication contributes significantly to the formation of KS lesions by either facilitating viral spread to the target site or releasing paracrine factors to support the growth of KS tumor cells. Therefore, KSHV reactivation from latency to lytic replication is not only important for viral propagation, but also critical for viral pathogenicity. My laboratory has been interested in the mechanisms used by KSHV to switch from latency to lytic life cycle. In the past a few years, several major accomplishments have been achieved. (1) Several KSHV immediate-early (IE) genes have been identified in our lab. Since the reactivation process is ...

Kaposis sarcoma-associated herpesvirus (KSHV) has an etiologic role in Kaposis sarcoma, primary effusion lymphoma and multicentric Castlemans disease. These diseases are most common in immunocompromised individuals, especially those with AIDS. Similar to all herpesviruses, KSHV infection is lifelong. KSHV infection in tumor cells is primarily latent, with only a small subset of cells undergoing lytic infection. During latency, the KSHV genome persists as a multiple copy, extrachromosomal episome in the nucleus. In order to persist in proliferating tumor cells, the viral genome replicates once per cell cycle and then segregates to daughter cell nuclei. KSHV only expresses several genes during latent infection. Prominent among these genes, is the latency-associated nuclear antigen (LANA). LANA is responsible for KSHV genome persistence and also exerts transcriptional regulatory effects. LANA mediates KSHV DNA replication and in addition, is responsible for segregation of replicated genomes to daughter

1. Dispenzieri A. Castleman disease. Cancer Treat Res 2008;142:293-330. 2. Liu AY, Nabel CS, Finkelman BS, et al. Idiopathic multicentric Castlemans disease: a systematic literature review. Lancet Haematol 2016;3(4):e163-e175. 3. Chan Kah-Lok, Lade S, Prince HM, et al. Update and new approaches in the threatment of Castleman disease. J Blood Med 2016;7:145-158. 4. Fajgenbaum DC, Uldrick TS, Bagg A, et al. International evidence-based consensus diagnostic criteria for HHV-8-negative/idiopathic multicentric Castleman disease. Blood 2017;129(12):1646-1657. 5. Simpson D. Epidemiology of Castleman disease. Hematol Oncol Clin North Am 2018;32(1):1-10. 6. Castleman B, Towe VW. Case report of the Massachusetts General Hospital weekly clinicopathological exercises, fouded by Richard C Cabot. N Engl J Med 1954;251(10):396-400.. 7. Keller AR, Hochholzer L, Castleman B. Hyaline-vascular and plasma-cell types of giant lymph node hyperplasia of the mediastinum and other localisation. Cancer ...

Since its discovery, improvements in treating Castleman disease and its variants have centered on interleukin-6 (IL-6). IL-6 was discovered from T-cell factors (BCDF or BSF-2), which induced B-cell maturation. Most symptoms of the plasma cell variant of Castleman disease are linked to the hyperfunction of IL-6, constitutively produced in the affected lymph nodes (1989), suggesting IL-6 is key in the pathogenesis of multicentric Castleman disease (MCD). The results of several studies have shown that most MCD symptoms and abnormal laboratory results are improved by anti-IL-6 MCD treatments, such as tocilizumab, a humanized anti-IL-6 receptor antibody, and siltuximab, an anti-IL-6 antibody ...

Castleman disease (CD) is a rare non-malignant lymphoproliferation of undetermined origin. Two major disease phenotypes can be distinguished: unicentric CD (UCD) and multicentric CD (MCD). Diagnosis confirmation is based on histopathological findings in a lymph node. We attempted to survey all cases of paediatric CD identified to date in France to set up a national registry aiming to improve CD early recognition, treatment and follow-up, within the context of a new national reference center (http://www.castleman.fr). In 2016, we e-mailed a questionnaire to members of the French paediatric immunohaematology society, the paediatric rheumatology society and the Reference Centre for Castleman Disease to retrospectively collect cases of paediatric CD (first symptoms before age 18 years). Anatomopathological confirmation was mandatory. We identified 23 patients (12 girls) with a diagnosis of UCD (n = 17) and MCD (n = 6) between 1994 and 2018. The mean age at first symptoms was 11.47 ± 4.23 years for UCD and

Congratulations to the international expert, our own Dr. Frits van Rhee, on his newest publication, A phase 2, open-label, multicenter study of the long-term safety of siltuximab (an anti-interleukin-6 monoclonal antibody) in patients with multicentric Castleman disease.. Be sure to check it out ...

Why research says understanding the overlap between Kaposi sarcoma-associated herpesvirus (KSHV) and human herpesvirus 8 (HHV8)-positive large B-cell lymphomas and associated diseases may lead to better outcomes.. ...

MALADIE DE CASTLEMAN PDF DOWNLOAD - Request PDF on ResearchGate | Maladie de castleman multicentrique: A propos dun cas | La maladie de Castleman est une affection rare, détiologie inconnue.

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PUBLIKÁCIÓK JEGYZÉKE KÖNYVEK 1. Fazekas A., Radnai M., Pelsőczi-K. I., Perényi J. Gnatológia. Medicina, Bp (146 p.) 2. Radnai M. A részleges kivehető fogpótlások. Medicina, Bp (215 p.) 3.

A UNC Lineberger study, led by Dirk Dittmer, PhD, reports the Kaposi sarcoma-associated herpes virus can commandeer a system involved in how host cells can affect changes in neighboring cells.

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Shinoda Masataka , Saito Kimihiro , Kondo Takao , Nakaoki Ariyoshi , Furuki Motohiro , Takeda Minoru , Yamamoto Masanobu , Schaich Thomas J. , van Oerle Bart M. , Godfried Herman P. , Kriele Paul A. C. , Houwman Evert P. , Nelissen Wim H. M. , Pels Gert J. , Spaaij Paul G. M. Jpn J Appl Phys 45(2B), 1311-1313, 2006-02-15 応用物理学会 被引用文献4件 ...