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1

Bortezomib induces apoptosis in T lymphoma cells and natural killer lymphoma cells independent of Epstein-Barr virus infection  

British Library Electronic Table of Contents (United Kingdom)

Abstract Epstein-Barr virus (EBV), which infects not only B cells, but also T cells and natural killer (NK) cells, is associated with multiple lymphoid malignancies. Recently, the proteasome inhibitor bortezomib was reported to induce apoptosis of EBV-transformed B cells. We evaluated the killing effect of this proteasome inhibitor on EBV-associated T lymphoma cells and NK lymphoma cells. First, we found that bortezomib treatment decreased the viability of multiple T and NK cell lines. No significant difference was observed between EBV-positive and EBV-negative cell lines. The decreased viability in response to bortezomib treatment was abrogated by a pan-caspase inhibitor. The induction of apoptosis was confirmed by flow cytometric assessment of annexin V staining. Additionally, cleavage o...

2011-01-01

2

LY294002 may overcome 5-FU resistance via down-regulation of activated p-AKT in Epstein-Barr virus-positive gastric cancer cells  

UK PubMed Central (United Kingdom)

BackgroundAs EBV-associated gastric cancer has unique features that are different from EBV (-) gastric cancer, EBV is considered to have a key role in gastric carcinogenesis. It...Full Text Available

3

Successful establishment of primary small airway cell cultures in human lung transplantation  

UK PubMed Central (United Kingdom)

BackgroundThe study of small airway diseases such as post-transplant bronchiolitis obliterans syndrome (BOS) is hampered by the difficulty in assessing peripheral airway function...Full Text Available

2009-01-01

4

Treatment of hematological malignancies with nonmyeloablative, HLA-haploidentical bone marrow transplantation and high dose, post-transplantation cyclophosphamide  

British Library Electronic Table of Contents (United Kingdom)

Hematopoietic stem cell transplantation provides the only potential curative option in many patients with hematological malignancies. Finding a suitably matched donor in a timely manner is often difficult. However, most patients have a partially HLA-mismatched (HLA-haploidentical) first-degree relative readily available. Historically, HLA-haploidentical bone marrow transplantation (BMT) has been considered extremely high risk due to high rates of life-threatening graft-versus-host disease (GVHD) and non-relapse mortality (NRM). Modifications of the stem cell graft, such as T-cell depletion, have resulted in poor rates of engraftment. We have recently completed a phase II clinical trial of nonmyeloablative HLA-haploidentical hematopoietic BMT followed by post-transplantation high-cyclophosp...

2011-01-01

5

Setting the standard in T-cell-depleted haploidentical transplantation and beyond  

British Library Electronic Table of Contents (United Kingdom)

Much progress has been made in the clinical, biological and technical aspects of the T-cell-depleted haploidentical hematopoietic stem cell transplantation (HSCT). Our experience demonstrates that infusing a megadose of extensively T-cell-depleted hematopoietic peripheral blood stem cells after an immuno-myeloablative conditioning regimen in acute leukemia patients ensures sustained engraftment with minimal GvHD without the need of any post-transplant immunosuppressive treatment. Since our first successful pilot study, our efforts have concentrated on developing new conditioning regimens, optimizing the graft processing and improving the post-transplant immunological recovery. The results we have so far achieved in high risk acute leukemia patients show that haploidentical transplantation ...

2011-01-01

6

Greater than the sum of their parts: Combination strategies for immune regeneration following allogeneic hematopoietic stem cell transplantation  

British Library Electronic Table of Contents (United Kingdom)

Cytoreductive conditioning regimes designed to allow for successful allogeneic hematopoietic stem cell transplantation (allo-HSCT) paradoxically are also detrimental to recovery of the immune system in general but lymphopoiesis in particular. Post-transplant immune depletion is particularly striking within the T cell compartment which is exquisitely sensitive to negative regulation, evidenced by the profound decline in thymic function with age. As a consequence, regeneration of the immune system remains a significant unmet clinical need. Over the past decade studies have revealed several promising therapeutic strategies to address ineffective lymphopoiesis and post-transplant immune deficiency. These include the use of cytokines such as IL-7, IL-12 and IL-15; growth factors and hormones li...

2011-01-01

7

Post-transplant monitoring of renal allografts: are we there yet?  

British Library Electronic Table of Contents (United Kingdom)

Transplantation has emerged as the therapy of choice for many patients with end organ failure. One of the major goals is to tailor immunosuppressive therapy to the individual needs of every patient to balance the risk for rejection and over-immunosuppression. This will require diagnostic tools that can detect harmful processes in the allograft early, and that can be measured repeatedly. This review will consider recent advances in our understanding of the molecular nature of these processes and how this information is being utilized to design novel diagnostic assays to non-invasively monitor allografts. Highlighted is the need for large-scale prospective multi-centre studies to validate assays that show early promise in single centre studies.

2009-01-01

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CD5 Is Dissociated from the B-Cell Receptor in B Cells from Bovine Leukemia Virus-Infected, Persistently Lymphocytotic Cattle: Consequences to B-Cell Receptor-Mediated Apoptosis  

UK PubMed Central (United Kingdom)

Bovine leukemia virus (BLV), a retrovirus related to human T-cell leukemia virus types 1 and 2, can induce persistent nonneoplastic expansion of the CD5+ B-cell population, termed...Full Text Available

2001-02-01

10

Native kidney reincarnation following a failed transplant  

International Nuclear Information System (INIS)

Full text: A 51-year-old woman with end stage renal failure secondary to Haemolytic Uraemic syndrome underwent a cadaveric renal transplant. A routine post transplant DTPA scan was performed which demonstrated satisfactory renal transplant perfusion and function. Incidental note was made of tracer uptake in the pelvis in the mid-line, which was suspected to be a uterine fibroid. This was confirmed on ultrasonography and at surgery. One week post transplantation the patient became acutely unwell and at laparotomy a perforated diverticular abscess was drained. Intraoperatively the transplant kidney was examined and the surgeon thought there was a area of infarction. This was confirmed on biopsy. As the patient's creatinine was rising a repeat DTPA study was performed. Perfusion and function of the transplant kidney was virtually absent while Doppler studies showed no flow. The patient however continued to ...

2002-05-04

11

Presence of preactivated T cells in hemodialyzed patients: their possible role in altered immunity.  

UK PubMed Central (United Kingdom)

Interleukin 2 (IL-2) and B-cell growth factors I and II (BCGF I and BCGF II) are lymphokines produced by T cells that play a major role in T- and B-cell cooperation. Peripheral blood lymphocytes from...Full Text Available

1986-10-01

12

Chronic inflammatory disease, lymphoid tissue neogenesis and extranodal marginal zone B-cell lymphomas  

UK PubMed Central (United Kingdom)

Chronic autoimmune or pathogen-induced immune reactions resulting in lymphoid neogenesis are associated with development of malignant lymphomas, mostly extranodal marginal zone B-cell lymphomas (MZBCLs)....Full Text Available

2009-08-01

13

Natural killer cell activity influences outcome after T cell depleted stem cell transplantation from matched unrelated and haploidentical donors  

British Library Electronic Table of Contents (United Kingdom)

Lytic activity and recovery of natural killer (NK) cells was monitored in pediatric patients with leukemias (ALL, AML, CML, JMML) and myelodysplastic syndromes after transplantation of T cell depleted stem cells from matched unrelated (n = 18) and mismatched related (haploidentical, n = 29) donors. CD34 + selection with magnetic microbeads resulted in 8 x 10^3/kg residual T cells. No post-transplant immune suppression was given. NK cells recovered rapidly after transplantation (300 CD56+/@mL at day 30, median), whereas T cell recovery was delayed (median: 12 CD3+/@mL at day 90). NK activity was measured as specific lysis of K 562 targets several times (mean: 3 assays per patient). Four temporal patterns of lytic activity could be differentiated: consistently low, consistently high, decreas...

2011-01-01

14

Role of Surgery After Chemotherapy in B-Cell Lymphoma of Thymus Causing Airway Compression and Right Ventricle Outflow Tract Obstruction  

British Library Electronic Table of Contents (United Kingdom)

Primary B-cell lymphoma of thymus is uncommon. We describe the case of a 23-year-old woman with a history of shortness of breath and distended neck veins of 1-month duration. A chest roentgenogram and computed tomographic chest scan of the showed a large anterior mediastinal mass. Tru-cut biopsy revealed primary B-cell lymphoma of thymus. She underwent chemotherapy with no symptomatic improvement. Post-chemotherapy computed tomographic scan of the chest showed no appreciable reduction in tumor size. Surgical excision was carried out with excellent results.

2011-01-01

15

Reversing B cell aging  

UK PubMed Central (United Kingdom)

Age-related alterations in the cellular composition of the B lineage are a major cause of the poor antibody response to vaccination and to infectious agents among the elderly population. The mechanisms...Full Text Available

16

Amplified B Lymphocyte CD40 Signaling Drives Regulatory B10 Cell Expansion in Mice  

UK PubMed Central (United Kingdom)

BackgroundAberrant CD40 ligand (CD154) expression occurs on both T cells and B cells in human lupus patients, which is suggested to enhance B cell CD40 signaling and play a role...Full Text Available

17

Telomeric DNA in normal and leukemic blood cells.  

UK PubMed Central (United Kingdom)

We studied telomeric DNA in leukemic cells as well as in normal T cells, B cells, monocytes, polymorphonuclear leukocytes, and bone marrow hematopoietic progenitor cells. No marked differences were...Full Text Available

1995-03-01

18

Modulation of B-cell endoplasmic reticulum calcium homeostasis by Epstein-Barr virus Latent Membrane Protein-1  

UK PubMed Central (United Kingdom)

BackgroundCalcium signaling plays an important role in B lymphocyte survival and activation, and is critically dependent on the inositol-1,4,5-tris-phosphate-induced...Full Text Available

19

Identification and Functional Relevance of de novo DNA Methylation in Cancerous B-Cell Populations  

UK PubMed Central (United Kingdom)

Epigenetic remodeling is a hallmark of cancer, with the frequent acquisition of de novo DNA methylation in CpG islands. However, the functional relevance of de novo...Full Text Available

2010-03-01

20

Establishment of an Immunoglobulin M Antibody-Forming Cell Response Model for Characterizing Immunotoxicity in Primary Human B Cells  

UK PubMed Central (United Kingdom)

Rodent models have been extensively utilized to identify putative human immunotoxicants; however, even when immunotoxicity is established, uncertainty remains whether the effects are predictive of human...Full Text Available

2009-12-01

 
 
 
 
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Chimeric Antigen Receptor Therapy for B-cell Malignancies  

UK PubMed Central (United Kingdom)

We presented data showing that the CART-19 cells expressing the 4-1BB signaling domain can have unprecedented and massive in-vivo expansion, traffic to tumor sites, persist long term in vivo, and induce...Full Text Available

22

Anti-CD47 antibody synergizes with rituximab to promote phagocytosis and eradicate non-Hodgkin lymphoma  

UK PubMed Central (United Kingdom)

SummaryMonoclonal antibodies are standard therapeutics for several cancers including the anti-CD20 antibody rituximab for B cell non-Hodgkin lymphoma (NHL). Rituximab and other...Full Text Available

2010-09-03

23

Yttrium Y 90 Ibritumomab Tiuxetan, Fludarabine, Radiation Therapy, and Donor Stem Cell Transplant in Treating Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma  

Science.gov (United States)

B-cell Chronic Lymphocytic Leukemia; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Splenic Marginal Zone Lymphoma; Waldenstrom Macroglobulinemia

2010-10-12

24

Resveratrol causes COX-2- and p53-dependent apoptosis in head and neck squamous cell cancer cells  

British Library Electronic Table of Contents (United Kingdom)

Cyclooxygenase-2 (COX-2) content is increased in many types of tumor cells. We have investigated the mechanism by which resveratrol, a stilbene that is pro-apoptotic in many tumor cell lines, causes apoptosis in human head and neck squamous cell carcinoma UMSCC-22B cells by a mechanism involving cellular COX-2. UMSCC-22B cells treated with resveratrol for 24 h, with or without selected inhibitors, were examined: (1) for the presence of nuclear activated ERK1/2, p53 and COX-2, (2) for evidence of apoptosis, and (3) by chromatin immunoprecipitation to demonstrate p53 binding to the p21 promoter. Stilbene-induced apoptosis was concentration-dependent, and associated with ERK1/2 activation, serine-15 p53 phosphorylation and nuclear accumulation of these proteins. These effects were blocked by ...

2008-01-01

25

The PTPN22 allele encoding an R620W variant interferes with the removal of developing autoreactive B cells in humans  

UK PubMed Central (United Kingdom)

Protein tyrosine phosphatase nonreceptor type 22 (PTPN22) gene polymorphisms are associated with many autoimmune diseases. The major risk allele encodes an R620W amino acid change that...Full Text Available

2011-09-01

26

Roles of the TNF receptor-associated factor (TRAF)2/3 binding site in differential B cell signaling by CD40 and its viral oncogenic mimic, latent membrane protein 1 (LMP1)  

UK PubMed Central (United Kingdom)

The Epstein-Barr virus protein, LMP1, is a functional mimic of the cellular receptor CD40, but signals to B lymphocytes in an amplified and sustained manner compared to CD40. LMP1 contributes...Full Text Available

2009-09-01

27

Induction of apoptosis in chicken bursal B cells  

Energy Technology Data Exchange (ETDEWEB)

Cell death in general can be a physiological process of cell number regulation in tissue, or it can be the result of exo or endogenous injuries, such a low-dose of radiation. Chicken B cell population in the bursa of Fabricius are very susceptible to PCD. Our present studies concern the development of radiation damage of chicken defence mechanisms. In 6 experiments pathogen free chicken were irradiated by gamma rays with the total doses of 0.25, 0.5, 1.0, 2.0 and 4.0 Gy. The induction of apoptosis was checked by Flow-cyto-meter 12 h after irradiation in bursa cell suspension. There is some increase in the number of induced apoptotic cells 12 h after irradiation at the dose 0.5-.4.0 Gy. There were no significant changes in the proportion of proliferating lymphocytes (G2 M), but cellularity decreased significantly at dose 2.0 and 4.0 Gy/12 h after irradiation. (author)

1997-03-01

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Molecular pathology of tumor-initiating cells: Lessons from Philadelphia chromosome-positive leukemia  

British Library Electronic Table of Contents (United Kingdom)

Recent improvements in cell purification and transplantation techniques have contributed to the identification of cell populations known as tumor-initiating cells (TIC). This discovery has led to the -cancer stem cell hierarchy- concept, which holds that tumors are organized as a hierarchy of malignant tissues sustained by such TIC. However, this concept remains controversial. In this review, we examine recent advances in cancer stem cell research that have been generated from studies of Philadelphia (Ph) chromosome-positive leukemia. The abnormal Ph chromosome, which arises from a translocation creating the BCR-ABL1 fusion gene, is most commonly associated with chronic myelogenous leukemia (CML) and precursor B cell acute lymphoblastic leukemia (B-ALL). Examination of the pathophysiology ...

2011-01-01

29

Diagnostic and Prognostic Utility of t(14;18) in Follicular Lymphoma  

British Library Electronic Table of Contents (United Kingdom)

Abstract Background: Follicular lymphoma (FL) is one of the most common non-Hodgkin's lymphomas of B cells, being closely associated with a t(14;18) translocation. Detection of t(14;18), which is present in 70-95% of FL, might aid in FL diagnosis. Objective: To compare the efficacy of routine polymerase chain reaction (PCR) and fluorescence in situ hybridization (FISH) techniques in detecting t(14;18) in paraffin-embedded tissue samples of FL patients at different stages. Combined with other immunophenotypic biological determinants, detection of t(14;18) might help to determine patients at increased risk according to the FL International Prognostic Index (FLIPI) and therefore facilitate appropriate treatment. Design and Methods: This study was mainly based on a retrospective examination of...

2007-01-01

30

Efficient natural defense mechanisms against Listeria monocytogenes in T and B cell-deficient allogeneic bone marrow radiation chimeras. Preactivated macrophages are the main effector cells in an early phase after bone marrow transfer  

International Nuclear Information System (INIS)

Radiation chimeras in the early phase after bone marrow transplantation are a good model to study the efficiency of the body's nonspecific defense system represented by macrophages (M phi), polymorphonuclear cells (PMN), and NK cells. These cell types are present in large numbers in spleen and liver at that time, whereas the specific immune system represented by T and B cells is functionally deficient. We previously reported enhanced activities in vitro of M phi (and PMN) from recipient animals in an early phase after allogeneic bone marrow transfer. We here demonstrate that these activities result in enhanced spontaneous resistance against Listeria monocytogenes in vivo: CFU of L. monocytogenes in spleen and liver 48 h after infection were about 1 or 2 to 4 log steps less than in untreated control mice of donor or host haplotype. This enhanced resistance decreased over the 4-mo period after marrow transfer. Preactivated M phi were identified ...

31

Long-term IL-2 therapy after transplantation of T cell depleted stem cells from alternative donors in children  

British Library Electronic Table of Contents (United Kingdom)

The aim of this pilot study was to evaluate the feasibility of long-term subcutaneous application of low-dose IL-2 in children with malignancies at very high risk of relapse who underwent highly T cell and B cell depleted HLA-identical (MUD) or full haplotype mismatched related hematopoetic stem cell transplantation. We studied 11 patients with acute leukemias/myelodysplastic syndrome and juvenile myelomonocytic leukemia (active disease and/or second stem cell transplantation, n = 8; >=CR 2, n = 2) and relapsed or progressive Ewings sarcoma (n = 2) who received prophylactic IL-2 treatment for a high probability of disease recurrence after allo-HSCT. Toxicities from IL-2 were transient fever, fatigue and local inflammation. In one patient GvHD grade III with no clear association to IL-2 adm...

2011-01-01

32

Successful treatment of skin infiltration in childhood hematological malignancies with total skin electron beam therapy. A report of two cases  

Energy Technology Data Exchange (ETDEWEB)

Two children with cutaneous lymphoma and leukemia who were treated with total skin electron beam therapy (TSEB) are described here. Patient 1. A 7-year-old boy was admitted because of a mass over the bilateral parotis and anemia. The white blood cell count on admission was 5,000/ul. Bone marrow examination revealed 70 per cent monoblasts (M5a type by FAB classification). Complete remission was obtained following the regimen of daunomycin, cytosine arabinoside, 6-mercaptopurine and prednisolone. He was again admitted because of a skin nodule on the left thigh 19 months after initial diagnosis. A biopsy of the skin nodule demonstrated monoblastic infiltration. He received 20 Grays (Gy) to the left thigh and this led to resolution of the skin nodule. At that time, other skin nodules appeared on the right upper and lower extremities. He was treated with TSEB. Daily doses of 1 Gy were given twice a week with a 4 MeV electron beam and a total dose of 10 Gy was administered over a period of 4 ...

1988-07-01

33

Radiation therapy for gastrointestinal lymphomas: indications and techniques  

International Nuclear Information System (INIS)

Gastrointestinal lymphomas are almost exclusively of a non Hodgkin's type. The Western form is characterized by a higher incidence of stomach location (50 %), a MALT type (mucosa associated lymphoid tissue) (40 %), a B-cell type (90 %), and a high grade (55 %). Chronic infection with Helicobacter pylori is an important risk factor. Mediterranean lymphomas form a particular clinical and pathological entity with diffuse involvement of the small bowel and are frequently being associated with a chronic malabsorption disorder. Eradication of Helicobacter pylori in early lymphomas, and the use of tetracyclines in early Mediterranean lymphomas, have been shown to induce durable remissions. For more advanced gastric lymphomas, treatment usually consists of anthracycline-based chemotherapy followed by involved field radiotherapy. Surgery is usually reserved for complications such as perforation or bleeding, or in some selected cases for salvage after failure of non-surgical ...

34

Photoaffinity labeling of ATP and NAD"+ binding sites on recombinant human interleukin 2  

International Nuclear Information System (INIS)

Interleukin 2 (IL-2) is a T-cell-derived lymphokine critical in the activation and proliferation of T cells, B cells, and lymphokine-activated killer cells. It is a glycoprotein of #approx#15,500 daltons that is synthesized and secreted after activation by antigen or mitogen. By using the analogs 8-azidoadensoine 5'-[#gamma#-"3"2P]triphosphate ([#gamma#-"3"2P]8N_3ATP) and nicotinamide 2-azidoadenine [adenylate-"3"2P]dinucleotide ([#alpha#-"3"2P]2N_3NAD"+) as photoaffinity probes, the authors have detected specific, metal ion-requiring nucleotide binding sites on recombinant human IL-2 (rhIL-2). The specificity of these nucleotide interactions with rhIL-2 was demonstrated by saturation effects and by competition by the parent nucleotides at physiologically relevant concentrations. Saturation of photoinsertion into rhIL-2 occurred at 50 #mu#M [#gamma#-"3"2P]8N_3ATP. Saturation of photoinsertion with [#alpha#-"3"2P]2N_3NAD"+ was observed at 180 ...

35

Committed T lymphocyte stem cells of rats. Characterization by surface W3/13 antigen and radiosensitivity  

Energy Technology Data Exchange (ETDEWEB)

The existence of stem cells committed to the T lymphoid lineage was deduced from studying how rat T and B stem cells differ in their expression of membrane W3/13 antigen and in their susceptibility in vivo to gamma irradiation. Stem cell activity of rat bone marrow and fetal liver was measured in long-term radiation chimeras using B and T cell alloantigenic surface markers to identify the progeny of donor cells. Monoclonal mouse anti-rat thymocyte antibody W3/13 labeled approximately 40% of fetal liver cells and 60-70% of young rat bone marrow cells (40% brightly, 25% dimly). Bright, dim, and negative cells were separated on a fluorescence-activated cell sorter. All B and T lymphoid stem cells in fetal liver were W3/13 bright, as were B lymphoid stem cells in bone marrow. W3/13 dim bone marrow had over half the T cell repopulating activity of unseparated marrow but gave virtually no B cell repopulation. In further experiments, the ...

1981-01-01

36

Characterization of chicken octamer-binding proteins demonstrates that POU domain-containing homeobox transcription factors have been highly conserved during vertebrate evolution  

Energy Technology Data Exchange (ETDEWEB)

The DNA sequence motif ATTTGCAT (octamer) or its inverse complement has been identified as an evolutionarily conserved element in the promoter region of immunoglobulin genes. Two major DNA-binding proteins that bind in a sequence-specific manner to the octamer DNA sequence have been identified in mammalian species--a ubiquitously expressed protein (Oct-1) and a lymphoid-specific protein (Oct-2). During characterization of the promoter region of the chicken immunoglobulin light chain gene, the authors identified two homologous octamer-binding proteins in chicken B cells. when the cloning of the human gene for Oct-2 revealed it to be a member of a distinct family of homeobox genes, they sought to determine if the human Oct-2 cDNA could be used to identify homologous chicken homeobox genes. Using a human Oct-2 homeobox-specific DNA probe, they were able to identify 6-10 homeobox-containing genes in the chicken genome, demonstrating that the ...

1990-02-01