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Lymphoma Cells (lymphoma + cell)
Kinds of Lymphoma Cells Terms modified by Lymphoma Cells Selected AbstractsPediatric ALK+ anaplastic large cell lymphoma with t(3;8)(q26.2;q24) translocation and c-myc rearrangement terminating in a leukemic phaseAMERICAN JOURNAL OF HEMATOLOGY, Issue 1 2007Sara Monaco Abstract Pediatric ALK-positive anaplastic large cell lymphoma (ALK+ ALCL) is usually associated with a favorable prognosis. ALK+ ALCL associated with a leukemic phase is uncommon, but has been associated with an aggressive clinical course and unfavorable prognosis. Overexpression of c-myc has been shown to be a consistent finding in ALK+, but not ALK-negative ALCL (ALK, ALCL), and the c-myc gene is considered a downstream target of deregulated ALK signaling. We describe a pediatric ALK+ ALCL with a leukemic phase at relapse. Similar to other rare cases described in the literature, it followed an aggressive clinical course despite multiple regimens of chemotherapy and bone marrow transplantation. Lymphoma cells showed aberrant ALK expression and c-myc overexpression. In addition to the characteristic t(2;5)(p23;q35) translocation, a t(3;8)(q26.2;q24) translocation was also present, and c-myc gene rearrangement was confirmed by FISH analysis. The findings in this case demonstrate the association of peripheral blood leukemic involvement and aggressive clinical course, and suggest that other factors, such as c-myc rearrangement, may be responsible for the aggressive clinical behavior in ALK+ ALCL. Am. J. Hematol., 2006. © 2006 Wiley-Liss, Inc. [source] Prognosis of follicular lymphomasHEMATOLOGICAL ONCOLOGY, Issue 2 2006Stefano Luminari Abstract Follicular lymphoma (FL) is as an indolent neoplasia with median survival measured in decades. Nevertheless, some patients have poor progression-free survival and overall survival. Several treatment approaches are proposed for patients with FL, however criteria to rationalize treatment decisions are lacking. Studies have been performed to build up prognostic indices that are useful for defining risk-adapted treatment recommendations. Available indices are based on parameters that have an independent role in predicting patient survival and that are variably correlated with the features of the disease, with the characteristics of the patient and with the effects of treatment. Two new prognostic indices have recently been proposed for FL: the Italian Lymphoma Intergroup (ILI) index and the Follicular Lymphoma International prognostic Index (FLIPI). Both indices are based on large series of patients and exhibit differences in their ability to discriminate between patients with different probabilities of survival. In recent years, with the advent of gene expression profile studies, our knowledge of the biology of FL is changing as novel data become available about the lymphoma cell and about the role of the microenvironment; these studies have already provided novel prognostic tools for identifying patients with more aggressive disease. Further data and large international cooperative studies are needed to translate into clinical practice the novel acquisitions of biology and therapeutics. Copyright © 2006 John Wiley & Sons, Ltd. [source] Human T-lymphotropic virus type-1 related adult T-cell leukemia/lymphoma presenting as a parotid mass diagnosed by fine-needle aspiration biopsyDIAGNOSTIC CYTOPATHOLOGY, Issue 5 2004Guo-Xia Tong M.D., Ph.D. Abstract A 48-yr-old black woman with a history of blood transfusions for menorrhagia secondary to uterine fibroids but no known Caribbean association presented with a 6-wk history of a rapidly enlarging right parotid mass. At the time of presentation, she could not close her right eye. An aspiration biopsy showed small, medium, and large lymphoma cells with angulated nuclei, red macronucleoli, and basophilic cytoplasm with fine vacuoles. Flow cytometry indicated a (CD25+/CD7,) T-cell lineage, suggesting an human T-lymphotropic virus (HTLV) 1-related T-cell leukemia/lymphoma, which was confirmed by polymerase chain reaction (PCR)-based amplification on DNA extracted from fresh tissue with specific oligonucleotide primers for HTLV-1 DNA sequence. Histology showed interstitial infiltration and destruction of the parotid parenchyma by lymphoma cells without involvement of adjacent lymph nodes. Total body CT scan and magnetic resonance imaging (MRI) studies were negative for lymphadenopathy but showed liver metastasis. To our knowledge, this is the first reported case of HTLV-1-related primary parotid lymphoma as the initial presentation of adult T-cell leukemia/lymphoma. Diagn. Cytopathol. 2004;31:333,337. © 2004 Wiley-Liss, Inc. [source] Cytologic features of recurrent lymphoma involving the urinary bladderDIAGNOSTIC CYTOPATHOLOGY, Issue 3 2004Adam M. Quinn D.O. Abstract Recurrent lymphoma of the bladder only occasionally presents with genitourinary symptoms, and there are very few cases in the literature reporting the cytologic findings of involvement of the urinary bladder by lymphoma. We report the findings from a case of diffuse large B-cell lymphoma with immunoblastic morphology that was identified in a bladder barbotage specimen of a 77-year-old man who presented with recurrent urinary tract infection and hematuria. We describe the cytomorphological features of lymphoma cells in the urine and discuss the differential diagnoses. Correlation of cytologic findings with immunohistochemical results is crucial in the diagnosis of lymphoma involving the urinary bladder. Diagn. Cytopathol. 2004;31:185,188. © 2004 Wiley-Liss, Inc. [source] PARTIAL REGRESSION OF DUODENAL LESIONS OF INTESTINAL FOLLICULAR LYMPHOMA AFTER ANTIBIOTIC TREATMENTDIGESTIVE ENDOSCOPY, Issue 4 2010Tomonori Yaguchi A 51-year-old man was referred to our hospital because of duodenal lesions of lymphoma. Endoscopy showed multiple tiny smooth whitish granules in the second portion of the duodenum including the papilla of Vater. Biopsy specimens showed medium-sized centrocyte-like cells forming lymphoid follicles, and immunohistology showed positive staining for bcl-2 and CD10. A small bowel series showed multiple granular lesions extending from the second portion of the duodenum to the proximal jejunum and the proximal ileum. On the basis of these findings, the tumor was diagnosed as stage I follicular lymphoma (FL). Although the patient was negative for Helicobacter pylori, he underwent antibiotic treatment. The lesions improved 3 months after antibiotic treatment, but biopsy specimens showed residual lymphoma cells. The patient therefore received combination chemotherapy with rituximab. Endoscopy 4 months later showed regression of FL, and there was no evidence of recurrence during 3 years of follow up. The partial regression of duodenal lesions of intestinal FL may be due to the effect of antibiotic treatment. [source] CONCURRENT GASTRIC AND COLONIC LOW-GRADE MUCOSA-ASSOCIATED LYMPHOID TISSUE LYMPHOMATA IN A PATIENT WITHOUT HELICOBACTER PYLORI INFECTIONDIGESTIVE ENDOSCOPY, Issue 1 2003HIROYUKI OKADA Mucosa-associated lymphoid tissue (MALT) lymphomata observed simultaneously in the stomach and colon are rare. We report concurrent gastric and colonic low-grade MALT lymphomata that originated from the same clone in a 58-year-old Japanese man without Helicobacter pylori infection. Endoscopy showed multiple erosive lesions in the gastric body and antrum, and a single flat elevation with an irregular margin in the sigmoid colon. Histopathological findings of both lesions suggested low-grade MALT lymphoma. Lymphoepithelial lesions were evident in the gastric lesions, but not in the colonic lesion. Southern blot analysis of lymphoma cells revealed the same immunoglobulin heavy-chain rearrangement pattern. The chromosomal translocation t(11;18)(q21;q21) was also observed. After six courses of cyclophosphamide, doxorubicin, vincristine and predonisolone, the gastric lesions disappeared endoscopically, while the colonic lesion persisted. A sigmoidectomy was consequently performed. The chromosomal translocation may be related to the pathogenesis of the present MALT lymphoma case without H. pylori infection. It is interesting that the gastric and colonic lesions differed in response to treatment and in their endoscopic and histologic features, despite having the same origin. [source] 3,-azido-3,-deoxythymidine induces deletions in L5178Y mouse lymphoma cells,,ENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 3-4 2007Jianyong Wang Abstract 3,-Azido-3,-deoxythymidine (AZT), a nucleoside analogue used for the treatment of acquired immunodeficiency syndrome (AIDS), induced a significant dose-related increase in the thymidine kinase (Tk) mutant frequency (MF) in L5178Y/Tk+/, 3.7.2C mouse lymphoma cells. Treatment with 1 mg/ml (3,742 ,M) AZT for 24 hr resulted in a MF of 407 × 10,6 compared to a control MF of 84 × 10,6. The MFs of the large and small colony mutants resulting from AZT exposure were 142 × 10,6 and 265 × 10,6, respectively. One hundred and fifty mutants from the 1 mg/ml (3,742 ,M) AZT-treated culture and sixty-nine mutants from independent untreated cultures were isolated and analyzed. LOH analysis using a heteromorphic microsatellite locus located in the Tk gene was performed to determine the presence or absence of the Tk+ allele. Eight other microsatellite markers spanning the entire mouse chromosome 11 also were examined for heterozygosity to determine the extent of LOH. In addition, Tk gene dosage analysis was conducted using Real-Time PCR in those mutants showing LOH at the Tk locus. The presence of only one Tk allele based on Real-Time PCR indicated that the mutant resulted from deletion while the presence of two alleles was consistent with a recombination event. More mutants from the AZT-treated culture showed Tk LOH than did independent mutants from the untreated cultures (91% vs. 64%) and the induced mutants also showed distinct chromosome 11 LOH patterns. The mutation spectrum of mutants from AZT-treated cells was also significantly different from that of spontaneous mutants. More deletions and fewer intragenic mutations were observed in the mutants from the AZT-treated culture than independent mutants from the untreated control. Our data indicate that AZT primarily induced LOH mutations in L5178Y mouse lymphoma cells and a large number of LOH mutations resulted from deletions. Environ. Mol. Mutagen., 2007. Published 2007 Wiley-Liss, Inc. [source] Over-expression of CCL3,,MIP-1, in a blastoid mantle cell lymphoma with hypercalcemiaEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 5 2010Norimichi Hattori Abstract We analyzed a case with the blastoid variant of mantle cell lymphoma (MCL-BV), a rare subtype of B-cell lymphoma, presenting with marked hypercalcemia at diagnosis. Enzyme-linked immunosorbent assay (ELISA) showed elevated serum levels of interleukin-6 (IL-6), tumor necrosis factor-, (TNF-,), macrophage inflammatory protein-1, (MIP-1,), and type I collagen telopeptide, but not parathyroid hormone, calcitriol or parathyroid hormone-related peptide at diagnosis, suggesting local osteoclastic hypercalcemia in this case. By reverse transcription polymerase chain reaction (RT-PCR) analysis, we found predominant expression of mRNA for MIP-1, in addition to those for receptor-activator of nuclear-factor kappa B ligand (RANKL), TNF-,, and IL-6 in lymphoma cells obtained from the patient. Furthermore, recombinant MIP-1, significantly stimulated 3H-thymidine uptake by isolated MCL cells in vitro. Treatment with intravenous fluids, bisphosphonate, and methylprednisolone followed by combination chemotherapy promptly corrects the hypercalcemia and successfully induced complete remission, which was accompanied by a decrease of these cytokines in the serum, including MIP-1,. In the present case, MIP-1,, an osteoclast-activating factor produced by mantle lymphoma cells, may contribute to the development of hypercalcemia. It likely acts through RANKL expression in tumor cells and/or stroma cells, as indicated in multiple myeloma (MM) and adult T-cell leukemia/lymphoma (ATLL). Furthermore, MIP-1, is also involved in the development of an aggressive phenotype on MCL by stimulating proliferation of these lymphoma cells. In summary, the present study demonstrated that MIP-1, is an important factor in the development of both hypercalcemia and an aggressive phenotype in some types of B-cell lymphoma. [source] Effect of drug-induced cytotoxicity on glucose uptake in Hodgkin's lymphoma cellsEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 2 2006Ursula Banning Abstract:,Background:,In Hodgkin's lymphoma, F-18-fluoro-deoxy- d -glucose positron emission tomography (FDG-PET) is used for staging and response evaluation after chemotherapy. However, drug-mediated downregulation of glucose uptake in viable Hodgkin's lymphoma cells might limit the use of FDG-PET. Methods:,We analyzed the effect of etoposide on cell viability and uptake of F-18-fluoro-deoxy- d -glucose or the glucose analog 2-[N -(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxyglucose (2-NBDG) in vitro. Results:,Etoposide induced a dose-dependent cytotoxicity in HDLM-2 cells which was significantly correlated with reduced FDG uptake. However, it also significantly increased the portion of viable cells which did not take up 2-NBDG. Interestingly, etoposide-induced cytotoxicity was mainly mediated via caspase-dependent mechanisms, whereas the cell death induced by deprivation of glucose was mediated via caspase-independent mechanisms. Conclusion:,Etoposide-mediated reduction of glucose uptake by Hodgkin's lymphoma cells is mainly caused by cell death. In a small fraction of viable cells, etoposide might downregulate glucose transporters and/or hexokinase activity and by that inhibit glucose uptake. This, however, might not lead to false-negative results of response evaluation in Hodgkin's lymphoma patients after chemotherapy, because inhibition of glucose uptake itself seems to be a strong inducer of cell death. Altogether, this study provides important in vitro evidence to clarify the mechanisms by which FDG-PET monitors the effect of anti-cancer treatment in Hodgkin's lymphoma patients. [source] Synergistic activation of interferon-, gene transcription by the viral FLICE inhibitory protein of Kaposi's sarcoma-associated herpesvirus and type,I IFN activatorsEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 10 2007Nathalie Cloutier Abstract Expression of Kaposi's sarcoma-associated herpesvirus v-FLIP leads to the spindle-shape morphology of endothelial cells and is essential for the survival of primary effusion lymphoma cells. Activation of the NF-,B transcription factor by v-FLIP is responsible for these effects. Considering that the interferon-, (ifn- ,) gene is regulated partly through NF-,B, we sought to determine whether v-FLIP would activate the expression of the ifn -, gene. Our results indicate that when v-FLIP is expressed by itself it has no effect on ifn -, gene activation but when it is combined with known IFN-, inducers, a synergistic activation of the ifn -, gene occurs. This effect is strictly dependent on NF-,B and is mediated through the positive regulatory domain,II of the IFN-, promoter. Furthermore, we report that protection from Fas-induced cell-death by v-FLIP is observed whether or not the type,I IFN signaling pathway is activated. Our work therefore contributes to increase our knowledge on v-FLIP, highlighting the complex immunomodulatory properties of this anti-apoptotic viral protein. [source] Impaired lymphocyte development and function in Clast5/Stra13/DEC1-transgenic miceEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 5 2004Mika Seimiya Abstract Clast5/Stra13/DEC1 is a member of the helix-loop-helix family of transcriptional repressors. We have previously shown that Clast5 is rapidly down-regulated upon B,cell activation and its overexpression inhibits cell cycle progression in B,lymphoma cells. In the present study, we show that Clast5 expression is developmentally regulated during B,cell differentiation, being expressed at theprogenitor B,cells, down-regulated at the precursor B,cells, elevated in immature and mature resting B,lymphocytes, and down-regulated again in germinal center B,ells. To investigate the function of Clast5 in regulating lymphocyte development, we have generated transgenic mice expressing Clast5 in B- and T-lineage cells (Clast5-Tg). Clast5-Tg mice grew and bred normally but their spleen and thymus cellularity was reduced compared with control littermates. The development of B,cells in the bone marrow and T,cells in the thymus was impaired, with the expansion of progenitor B and T,cells most strongly affected. The frequency of IL-7-responsive cells in the bone marrow of Clast5-Tg mice was reduced by >80% and their proliferative response to IL-7 was also compromised. Mature B,cells from Clast5-Tg mice were hyporesponsive to antigen receptor cross-linking and exhibited mild reduction in the proliferative response to CD40 ligation or lipopolysaccharide stimulation. Moreover, thedevelopment of germinal center B,cells and antibody production against a T-dependent antigen were reduced in Clast5-Tg mice. These results reveal a critical role for Clast5/Stra13/DEC1 in negatively regulating lymphocyte development and function in vivo. [source] NF-ATc2 induces apoptosis in Burkitt's lymphoma cells through signaling via the B cell antigen receptorEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 1 2003Eisaku Kondo Abstract Cross-linking of the B cell antigen receptor (BCR) with an anti-IgM antibody has been shown to induce dramatic apoptosis in type I Burkitt's lymphoma (BL) cells. However, the apoptotic mechanism triggered via BCR remains unknown. Here we reports a mechanism of BCR ligation-induced apoptosis involving protein phosphatase calcineurin and its specific substrate, transcriptional factor NF-AT. In response to BCR cross-linking, endogenous calcineurin was rapidly activated, and this facilitated nuclear translocation of NF-ATc2, a subtype of NF-AT members. Interestingly, nuclear-imported NF-ATc2 functioned pro-apoptotically in BL cells. The effect of NF-ATc2 was efficiently blocked with FK506, which prevented its nuclear translocation through inactivation of calcineurin. In addtion, TR3 induction during BCR cross-linking was reduced by FK506 and the VIVIT peptide, which is a highly selective inhibitor for NF-AT. This strongly suggests that activation of NF-ATc2 by calcineurin is essential for TR3 recruitment, and that TR3 can be considered as a candidate for death effector in BCR-mediated apoptosis. Therefore, NF-ATc2 plays a crucial role in BCR-mediated apoptosis in type IBL, providing greater insight into unique BL characteristics through BCR signaling. [source] Cloning of MMP-26FEBS JOURNAL, Issue 11 2000A novel matrilysin-like proteinase A cDNA encoding a novel human matrix metalloproteinase (MMP), named MMP-26, was cloned from fetal cDNA. The deduced 261-amino-acid sequence is homologous to macrophage metalloelastase (51.8% identity). It includes only the minimal characteristic features of the MMP family: a signal peptide, a prodomain and a catalytic domain. As with MMP-7, this new MMP does not comprise the hemopexin domain, which is believed to be involved in substrate recognition. A study of MMP-26 mRNA steady states levels reveals, among the tissue examined, a specific expression in placenta. MMP-26 mRNA could also be detected in several human cell lines such as HEK 293 kidney cells and HFB1 lymphoma cells. Recombinant MMP-26 was produced in mammalian cells and used to demonstrate a proteolytic activity of the enzyme on gelatin and ,-casein. [source] Role of DNA polymerase , in tolerance of endogenous and exogenous DNA damage in mouse B cellsGENES TO CELLS, Issue 2 2006Akiko Ukai DNA polymerase , (Pol,) is a family A polymerase that contains an intrinsic helicase domain. To investigate the function of Pol, in mammalian cells, we have inactivated its polymerase activity in CH12 mouse B lymphoma cells by targeted deletion of the polymerase core domain that contains the catalytic aspartic acid residue. Compared to parental CH12 cells, mutant cells devoid of Pol, polymerase activity exhibited a slightly reduced growth rate, accompanied by increased spontaneous cell death. In addition, mutant cells showed elevated sensitivity to mitomycin C, cisplatin, etoposide, ,-irradiation and ultraviolet (UV) radiation. Interestingly, mutant cells were more sensitive to the alkylating agent methyl methanesulfonate (MMS) than parental cells. This elevated MMS sensitivity relative to WT cells persisted in the presence of methoxyamine, an inhibitor of the major base excision repair (BER) pathway, suggesting that Pol, is involved in tolerance of MMS through a mechanism that appears to be different from BER. These results reveal an important role for Pol, in preventing spontaneous cell death and in tolerance of not only DNA interstrand cross-links and double strand breaks but also UV adducts and alkylation damage in mammalian lymphocytes. [source] Peripheral T-cell lymphoma presenting as myelofibrosis with the expression of basic fibroblast growth factorGERIATRICS & GERONTOLOGY INTERNATIONAL, Issue 4 2009Masayuki Kikukawa Myelofibrosis is often observed in chronic myeloproliferative disorders (CMPD), but non-Hodgkin's lymphoma with diffuse myelofibrosis is rare. We describe an elderly case with peripheral T-cell lymphoma-unspecified (PTCL) presenting as diffuse myelofibrosis. Bone marrow biopsy revealed infiltration of atypical lymphocytes and diffuse myelofibrosis without any increase in megakaryocytes. To discuss the pathogenesis of fibrosis, we examined cytokines relative to fibrosis using immunostaining. The expression of basic fibroblast growth factor (bFGF) was diffusely detected in the area of extracellular matrix of bone marrow. In addition, in situ hybridization revealed that infiltrating lymphoma cells expressed bFGF mRNA. Basic FGF, originally identified based on its mitogenicity for fibroblasts, has multiple potential, influencing neoangiogenesis, bone marrow fibrosis and the proliferation of tumor cells. Basic FGF might play an important role in the pathogenesis of myelofibrosis in the present case. [source] 18F-FDG uptake and its clinical relevance in primary gastric lymphomaHEMATOLOGICAL ONCOLOGY, Issue 2 2010Jun Ho Yi Abstract We studied the clinical relevance of 18F-fluorodeoxyglucose (18F-FDG) uptake in patients with primary gastric lymphoma underwent positron emission tomography (PET)/ computed tomography (CT) scan. Forty-two patients with primary gastric lymphoma were analysed: 32 diffuse large B-cell lymphomas (DLBCL) and 10 extranodal marginal zone B-cell lymphomas of mucosa-associated lymphoid tissue (MALT lymphomas). The PET/CT scans were compared with clinical and pathologic features, and the results of CT and endoscopy. Nine patients were up-staged based on the results of their PET/CT scan compared to CT (seven DLBCLs, two MALT lymphomas) while six patients were down-staged by the PET/CT scan. The standard uptake value (SUV) was used as an indicator of a lesion with a high metabolic rate. The high SUVmax group, defined as an SUVmax , median value, was significantly associated with an advanced Lugano stage (p,<,0.001). Three patients with DLBCL, who showed an initially high SUVmax, died of disease progression. Among 24 patients for whom follow-up PET/CT scan with endoscopy was performed, 11 patients with ulcerative or mucosal lesions showed residual 18F-FDG uptake. All of these gastric lesions were grossly and pathologically benign lesions without evidence of lymphoma cells. In conclusion, PET/CT scan can be used in staging patients with primary gastric lymphoma; however, the residual 18F-FDG uptake observed during follow-up should be interpreted cautiously and should be combined with endoscopy and multiple biopsies of the stomach. Copyright © 2009 John Wiley & Sons, Ltd. [source] Extranodal NK/T-cell lymphoma: diagnosis and treatment cuesHEMATOLOGICAL ONCOLOGY, Issue 2 2008Ritsuro Suzuki Abstract Extranodal NK/T-cell lymphoma, nasal type (ENKL) is mostly endemic to East Asia. It predominantly occurs in the nasal or paranasal areas and less frequently in the skin. Most of the tumours show NK-cell, but rarely T-cell, phenotypes. The Epstein,Barr virus (EBV) genome can be usually detected in lymphoma cells. Geographic localization of ENKL matches the endemic distribution of EBV, suggesting that EBV plays an important role in lymphomagenesis. Originally, NK-cell and T-cell types were believed to present the same clinicopathologic characteristics, but recent data suggest more aggressive characteristics for the NK-cell phenotype. Although ENKL is sensitive to radiotherapy, it shows a poorer response to chemotherapeutic agents than other lymphomas due to expression of p-glycoprotein. Therefore, new therapeutic approaches must be considered. Several new clinical trials are now being conducted in East Asia. Copyright © 2008 John Wiley & Sons, Ltd. [source] Hyaluronan oligosaccharides sensitize lymphoma resistant cell lines to vincristine by modulating P-glycoprotein activity and PI3K/Akt pathwayINTERNATIONAL JOURNAL OF CANCER, Issue 5 2008Rosalía I. Cordo Russo Abstract Multidrug resistance (MDR) is one of the main reasons for failure of cancer therapy. It may be mediated by overexpression of ATP-dependent efflux pumps or by alterations in survival or apoptotic pathways. Fragments generated by enzymatic degradation of hyaluronan (oHA) were able to modulate growth and cell survival and sensitize MDR breast cancer cells to cytotoxic drugs. In this work the relationship between oHA and MDR in lymphoid malignancies was analyzed using murine lymphoma cell lines resistant to doxorubicin (LBR-D160) or vincristine (LBR-V160) and a sensitive line (LBR-). After oHA treatment, higher apoptosis levels were observed in the resistant cell lines than in the sensitive one. Besides, oHA sensitized LBR-D160 and LBR-V160 to vincristine showing increased apoptosis induction when used in combination with vincristine. Native hyaluronan failed to increase apoptosis levels. As different survival factors could be modulated by hyaluronan, we investigated the PI3K/Akt pathway through PIP3 production and phosphorylated Akt (p-Akt) and survivin expression was also evaluated. Our results showed that oHA decreased p-Akt in the 3 cell lines while anti-CD44 treatment abolished this effect. Besides, survivin was downregulated only in LBR-V160 by oHA. When Pgp function was evaluated, we observed that oHA were able to inhibit Pgp efflux in murine and human resistant cell lines in a CD44-dependent way. In summary, we report for the first time that oHA per se modulate MDR in lymphoma cells by decreasing p-Akt as well as Pgp activity, thus suggesting that oHA could be useful in combination with classical chemotherapy in MDR hematological malignancies. © 2007 Wiley-Liss, Inc. [source] Rapid induction of apoptosis in B-cell lymphoma by functionally isolated human antibodiesINTERNATIONAL JOURNAL OF CANCER, Issue 2 2006Johan Fransson Abstract Novel panning and screening methodology was devised to isolate high affinity human recombinant scFv antibody fragments with functionally associated properties in B lymphoma cells. The approach was used to generate a panel of apoptosis-inducing antibodies specific for antigens differentially expressed in B lymphoma vs. T leukaemia cells. The selections resulted in an antibody pool with near perfect selectivity (>99%) for the B lymphoma target cells. Randomly picked clones (72) revealed 7 unique antibody genotypes. Six of these rapidly induced apoptosis in target cells. Following the conversion to full IgGs, the antibodies were shown to be specific for HLA-DR/DP, the B-cell receptor , chain and for CD54/ICAM-1. The latter receptor was not previously associated with apoptotic properties in B-cell lymphomas. Anti-ICAM-1 IgG induced apoptosis in a broad range of B lymphoma cell lines and were shown by immunohistochemistry to bind strongly to B lymphoma tissue obtained from 5 different B lymphoma patients. The recombinant IgG antibodies had affinities in the subnanomolar (0.3 nM) to nanomolar (3 nM) range. The described technology is generally applicable for the rapid isolation of high affinity human antibodies with specificity for differentially expressed cell surface receptors with intrinsic negative or positive signalling properties from naïve phage libraries. © 2006 Wiley-Liss, Inc. [source] In vitro Epstein-Barr virus-immortalized lymphoma cell line carrying t(9;14)(p13;q32) chromosome abnormality, derived from splenic lymphoma with villous lymphocytesINTERNATIONAL JOURNAL OF CANCER, Issue 2 2006Masanori Daibata Abstract We herein describe splenic lymphoma with villous lymphocytes (SLVL) carrying t(9;14)(p13;q32). The t(9;14)(p13;q32) is a rare reciprocal chromosome translocation found in a subset of B-cell malignancies, mainly in low-grade non-Hodgkin's lymphomas. In t(9;14)(p13;q32), PAX-5 gene on 9p13 is involved with the immunoglobulin heavy-chain gene on 14q32. It has been thought that the deregulated expression of PAX-5 as a result of t(9;14)(p13;q32) may contribute to abnormal cell proliferation. Although continuous cell lines are invaluable tools for studying lymphomagenesis in the t(9;14)(p13;q32)-bearing lymphomas, establishment of such cell lines is extremely difficult since they are usually mature B-cell malignancies. In an attempt to transform the SLVL cells into a proliferating cell line, we examined the responses of the cells to infection by Epstein-Barr virus (EBV). SLVL cells were found to be susceptible to immortalization by EBV, resulting in a permanent cell line. The cell line, designated SL-15, possessed the t(9;14)(p13;q32). Genotype analysis and immunophenotype profiles confirmed that the cell line arose from the primary lymphoma cells. The cells had characteristic cytoplasmic villi. SL-15 cells has been growing over 2 years equivalent to 350,400 population doubling levels without proliferative crisis that is often observed in EBV-positive lymphoblastoid cell lines. Furthermore, SL-15 cells, when inoculated into nude mice, formed t(9;14)(p13;q32)-bearing tumors with cytoplasmic villi. The validated SLVL-derived cell line provide a useful model system to study molecular biology of t(9;14)(p13;q32)-bearing B-cell malignancies as well as lymphomagenesis of SLVL in vitro and in vivo. © 2005 Wiley-Liss, Inc. [source] c-Jun NH2 -terminal kinase (JNK)-dependent nuclear translocation of apoptosis-inducing factor (AIF) following engagement of membrane immunoglobulin on WEHI-231 B lymphoma cellsJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 5 2008Eiko Takada Abstract WEHI-231 B lymphoma cells have been employed for analysis of antigen-induced B cell unresponsiveness because these cells undergo cell cycle arrest in G1, accompanied by induction of apoptosis. In the present study, we examined the requirement for toxic small molecules apoptosis-inducing factor (AIF) and cytochrome c, and subsequent caspase activation in apoptotic cell death in WEHI-231 and CH31 B lymphoma cells following engagement of membrane immunoglobulin (mIg). Pan-caspase inhibitor BD-fmk blocked mIg-mediated increase in cells with sub-G1 DNA content, whereas it did not affect mIg-mediated loss of mitochondrial membrane potential and phosphatidylserine exposure on B cell membrane. Dominant-negative form of c-Jun NH2 -terminal kinase1 (JNK1) blocked the translocation of AIF into the nuclei and cytosol from the mitochondria in the WEHI-231 and CH31 cells following mIg engagement, whereas constitutively active form of JNK1 enhanced it. This AIF translocation was also blocked by Bcl-xL, but not by BD-fmk. Moreover, AIF-deficient clones via small interfering RNA (siRNA)-mediated method showed small increase in loss of mitochondrial membrane potential. After mIg engagement, the AIF-deficient clones displayed an enhanced sensitivity to mIg-mediated apoptosis, concomitant with translocation of a residual AIF into the nuclei, compared with control clone. Our findings are compatible with the notion that AIF has dual role, with a proapoptotic function in the nuclei and a distinct anti-apoptotic function in the mitochondria. These observations would be valuable for analysis of B cell unresponsiveness and hopefully for treatment of diseases involving B cell dysfunction. J. Cell. Biochem. 104: 1927,1936, 2008. © 2008 Wiley-Liss, Inc. [source] Role of O -linked ,- N -acetylglucosamine modification in the subcellular distribution of alpha4 phosphoprotein and Sp1 in rat lymphoma cellsJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 3 2005Shauna M. Dauphinee Abstract The mTOR alpha4 phosphoprotein is a prolactin (PRL)-downregulated gene product that is found in the nucleus of PRL-dependent rat Nb2 lymphoma cells. Alpha4 lacks a nuclear localization signal (NLS) and the mechanism of its nuclear targeting is unknown. Post-translational modification by O -linked ,- N -acetylglucosamine (O -GlcNAc) moieties has been implicated in the nuclear transport of some proteins, including transcription factor Sp1. The nucleocytoplasmic enzymes O -,- N -acetylglucosaminyltransferase (OGT) and O -,- N -acetylglucosaminidase (O -GlcNAcase) adds or remove O -GlcNAc moieties, respectively. If O -GlcNac moieties contribute to the nuclear targeting of alpha4, a decrease in O -GlcNAcylation (e.g., by inhibition of OGT) may redistribute alpha4 to the cytosol. The present study showed that alpha4 and Sp1 were both O -GlcNAcylated in quiescent and PRL-treated Nb2 cells. PRL alone or PRL,+,streptozotocin (STZ; an O -GlcNAcase inhibitor) significantly (P,,,0.05) increased the O -GlcNAc/alpha4 ratio above that in control quiescent cells. However, PRL,+,alloxan (ALX; an OGT inhibitor) or ALX alone did not decrease O -GlcNAcylation of alpha4 below that of controls and alpha4 remained nuclear. In comparison, PRL (±ALX/STZ) greatly increased Sp1 protein levels, caused a significant decrease in the GlcNAc/Sp1 ratio (P,,,0.05, n,=,3) as compared to controls and partially redistributed Sp1 to the cytosol. Finally, a 50% downregulation of OGT gene expression by small interfering RNA (i.e., siOGT) partially redistributed both alpha4 and Sp1 to the cytosol. The alpha4 protein partner PP2Ac had no detectable O -GlcNAc moieties and its nuclear distribution was not affected by siOGT. In summary, alpha4 and Sp1 contained O -GlcNAc moieties, which contributed to their nuclear targeting in Nb2 cells. © 2005 Wiley-Liss, Inc. [source] KSHV/HHV8-associated primary cutaneous plasmablastic lymphoma in a patient with Castleman's disease and Kaposi's sarcomaJOURNAL OF CUTANEOUS PATHOLOGY, Issue 2006Wenhua Liu Three months following the diagnosis of KS affecting a left cervical lymph node and Castleman's disease with bone marrow involvement, he presented with a subcutaneous, tender lesion on his left arm. A skin biopsy demonstrated a superficial and deep, interstitial-nodular infiltrate of severely atypical lymphoid cells showing plasmacytoid features, numerous mitotic figures, and frequent individual apoptotic tumor cells. The morphologic features were those of plasmablastic lymphoma (PBL). Immunohistochemical study showed that the lymphoma cells strongly expressed CD45, CD30, and KSHV/HHV8 latency-associated nuclear antigen. KSHV/HHV8 was also detected in the biopsy sections of the patient's KS and Castleman's disease. Epstein,Barr virus in situ hybridization was diffusely positive. In situ hybridization demonstrated ,-light chain restriction. Although KSHV/HHV8 has been individually associated with KS, Castleman's disease, and PBL, this appears to be the first reported case in which all three entities were present simultaneously in one person, suggesting a critical role of KSHV/HHV8 as a common denominator in the pathogenesis of these diseases. [source] C-KIT expression in primary cutaneous T-cell lymphomasJOURNAL OF CUTANEOUS PATHOLOGY, Issue 9 2004Tilmann C. Brauns Background:, Mutations of the stem cell factor receptor C-KIT play a major pathogenetic role in the development of different malignant diseases like human mastocytosis, myeloproliferative disorders, gastrointestinal stromal tumors, acute myelogenous leukemia, and sinonasal lymphomas. Furthermore, the expression of C-KIT has been described in Hodgkin's disease and nodal CD30+ anaplastic large cell lymphomas (ALCLs). As it is possible to inhibit C-KIT by innovative kinase inhibitors like STI571, it may be an attractive target for new therapeutical approaches. Therefore, we screened more than 50 different types of cutaneous T-cell lymphomas (TCLs) for the presence of C-KIT. Immunohistochemical stainings were performed on paraffin-embedded tissue sections using a polyclonal rabbit anti-human C-KIT antibody. Naphtol-ASD-chloroacetate esterase (NASDCE)-control stainings were performed on every positive sample to distinguish C-KIT-positive lymphoma cells from C-KIT-positive mast cells. Results:, We found weak expression of C-KIT in seven of 18 patients with primary cutaneous CD30+ ALCL, two of eight patients with primary cutaneous pleomorphic TCL, six of 18 patients suffering from mycosis fungoides, and three of five patients with Sezary's syndrome. Generally, only a very small population of the lymphoma cells expressed C-KIT. This finding indicates a difference to the systemic variant of CD30+ ALCL. The potential use of C-KIT targeting new therapeutical approaches is therefore discussed critically, because C-KIT expression is very rare in all investigated types of primary cutaneous lymphoma. [source] Clinicopathological features of gastric mucosa-associated lymphoid tissue lymphoma: A comparison with diffuse large B-cell lymphoma without a mucosa-associated lymphoid tissue lymphoma componentJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 7 2001Toru Hiyama Abstract Background and Aims: The aim of this study was to clinicopathologically distinguish the pathogenesis of gastric mucosa-associated lymphoid tissue (MALT) lymphoma and diffuse large B-cell lymphoma without a MALT lymphoma component (DLL). Methods: We investigated clinicopathological features of these gastric lymphomas including age, sex ratio, tumor location and depth, macroscopic appearance, and infection with Helicobacter pylori of these gastric lymphomas and hepatitis viruses in 24 patients with gastric low-grade MALT lymphoma, 10 patients with high-grade MALT lymphoma, and 19 patients with DLL. The frequency of H. pylori infection in lymphoma patients was compared with that in age- and sex-matched control subjects. Results: There was a predominance of females with MALT lymphoma (male to female ratio, 8/16 for low-grade MALT lymphomas and 1/9 for high-grade MALT lymphomas), and there was a predominance of males with DLL (male to female ratio, 13/6); the ratios differed significantly (P < 0.05). Ninety-two percent of low-grade MALT lymphomas and 80% of high-grade MALT lymphomas were confined to the mucosal and submucosal layers, but lymphoma cells invaded the muscular layer or more deeply in 74% of DLL. Helicobacter pylori infection occurred significantly more often in patients with low-grade MALT lymphoma than in age- and sex-matched controls (96 vs 67%, P < 0.01). Conversely, the frequency of H. pylori infection in DLL patients did not differ from that in controls. Conclusions: These data suggest that H. pylori infection may be associated with the development of gastric MALT lymphoma, but not DLL, and that MALT lymphoma and DLL may have a different pathogenesis. [source] Effects of L-Asparaginase on Plasma Amino Acid Profiles and Tumor Burden in Cats with LymphomaJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 4 2007A.K. LeBlanc Background: L-Asparaginase (Elspara), is an Escherichia coli -derived enzyme that depletes lymphoma cells of asparagine, inhibiting protein synthesis and resulting in cell death. The single agent response rate in cats with lymphoma and impact of L-asparaginase on plasma amino acid concentrations is unknown. Hypotheses: L-Asparaginase significantly reduces plasma asparagine concentrations and has demonstrable efficacy against untreated lymphoma in cats. Animals: Thirteen cats with confirmed lymphoma (LSA) of any anatomic site were given 1 dose 400 IU/kg IM) of L-asparaginase for initial LSA treatment. Methods: Plasma collected at 0, 2, and 7 days after L-asparaginase therapy was assayed for ammonia, asparagine, aspartic acid, glutamine, and glutamic acid concentrations. Cats were restaged 7 days later to assess tumor response. Results: Eight cats had T-cell LSA, 4 cats had B-cell LSA, and 1 cat's immunophenotype was unknown. Two complete and 2 partial responses to L-asparaginase were seen. Four cats had stable disease, and 5 cats had progressive disease. Ammonia and aspartic acid concentrations were increased from baseline at 2 and 7 days posttreatment. Asparagine concentrations were decreased from baseline at 2 days but not 7 days posttreatment. Glutamic acid concentrations were increased at day 2 compared to day 7 posttreatment but not compared to baseline. Glutamine concentrations were unchanged. Conclusions and Clinical Importance: L-Asparaginase significantly reduced asparagine concentrations within 2 days of treatment, but this effect was lost within 7 days. The apparent overall response rate of feline LSA to L-asparaginase in this study was 30%. [source] Spontaneous regression of malignant lymphoma of the breastPATHOLOGY INTERNATIONAL, Issue 7 2004Kuniko Iihara A complete spontaneous regression of diffuse large B cell lymphoma involving the right breast, confirmed by aspiration cytology, is reported. The patient visited a hospital due to the rapid growth of a tumor in the right breast. Five years previously she underwent a craniotomy for a brain tumor, diagnosed as B-cell malignant lymphoma, and received several courses of irradiation to the brain. Analysis of the breast tumor cells obtained by aspiration revealed lymphoma cells morphologically, which were similar to the tumor cells in the brain expressing CD20. While waiting for further examination, the tumor regressed rapidly and was not palpable after 20 days. An excisional biopsy of the breast exhibited no definite malignant lymphoma cells among a diffuse population of CD45RO and CD8-positive small lymphocytes. Nucleotide sequencing of HCDR3s of the brain tumor and breast tumor cells showed a completely matched sequence, revealing the breast mass to be a metastatic lesion from the tumor of the brain. Although there was no tumorous lesion, the patient received additional chemotherapy and has shown no sign of recurrence in the breast for 7 years. We were able to confirm that the breast lymphoma shown in the aspiration cytology was a metastatic one, which was not proven histologically prior to chemotherapy, and regard the present case as a malignant lymphoma of the breast showing spontaneous regression. The present case shows a rare occurrence of spontaneous regression of diffuse large B cell malignant lymphoma after aspiration and suggests that CD8-positive T cells might be related to the regression. [source] Toward a comprehensive quantitative proteome database: protein expression map of lymphoid neoplasms by 2-D DIGE and MSPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 17 2006Kazuyasu Fujii Abstract Using 2-D DIGE, we constructed a quantitative 2-D database including 309 proteins corresponding to 389 protein spots across 42 lymphoid neoplasm cell lines. The proteins separated by 2-D PAGE were identified by MS and assigned to the expression data obtained by 2-D DIGE. The cell lines were categorized into four groups: those from Hodgkin's lymphoma (HL) (4 cell lines), B cell malignancies (19 cell lines), T cell malignancies (16 cell lines), and natural killer (NK) cell malignancies (3 cell lines). We characterized the proteins in the database by classifying them according to their expression level. We found 28 proteins with more than a 2-fold difference between the cell line groups. We also noted the proteins that allowed multidimensional separation to be achieved (1) between HL cells and other cells, (2) between the cells derived from B cells, T cells and NK cells, and (3) between HL cells and anaplastic large cell lymphoma cells. Decision tree classification identified five proteins that could be used to classify the 42 cell lines according to differentiation. These results suggest that the quantitative 2-D database using 2-D DIGE will be a useful resource for studying the mechanisms underlying the differentiation phenotypes of lymphoid neoplasms. [source] Molecular targeted therapies for diffuse large B-cell lymphoma based on apoptosis profiles,THE JOURNAL OF PATHOLOGY, Issue 5 2010Saskia AGM Cillessen Abstract Diffuse large B-cell lymphoma (DLBCL) is the most common type of adult non-Hodgkin lymphoma and is treated with chemotherapy in combination with rituximab. Despite this aggressive therapy, the disease is fatal in 30,40% of patients. Inhibition of the apoptosis signalling pathways is strongly related to response to chemotherapy and eventual clinical outcome. In order to survive, lymphoma cells depend on disruption of the apoptosis pathway by mutations in apoptosis inducing genes or by continuous expression of anti-apoptotic proteins. The development of molecules targeting these apoptosis inhibitors provides a very promising opportunity to specifically target tumour cells without toxicity to non-malignant cells in DLBCL patients. Sensitivity for most of these antagonists can be predicted based on biological markers, suggesting the possibility of pre-defining patients who will most likely benefit from these targeted therapies. Experimental therapies aimed at restoring the upstream apoptosis pathway or targeting apoptosis inhibitors are currently being tested in clinical trials and are expected to be effective particularly in chemotherapy-refractory DLBCL, providing hope for patients who are refractory to current therapies. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source] 1141160720 Does the anti-proliferative action of ovine uterine serpin involve apoptosis?AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 6 2006MB Padua Ovine uterine serpin (OvUS) is the major progesterone-induced protein in the uterus of the pregnant sheep. This protein is a member of the serine proteinase inhibitor superfamily and it has been proposed to down-regulate uterine immune function during pregnancy to protect the fetus. In vitro experiments have shown that both the native and the recombinant (r) form of the protein can inhibit mitogen-induced lymphocyte proliferation and growth of canine primary osteogenic sarcoma cells, mouse lymphoma cells, human prostatic adenocarcinoma cells (PC-3 cell line) and bovine preimplantation embryos. The mechanism by which OvUS inhibits cell proliferation is still unknown. Accordingly, experiments were conducted to test whether rOvUS exerts its anti-proliferative action through apoptosis. In the first experiment, the anti-proliferative effect of rOvUS on PC-3 cells was tested to determine the minimal concentration effective at inhibiting proliferation. Proliferation was inhibited by concentrations of OvUS at 8 ,g/mL and higher. The incorporation of [3H]thymidine was 4043, 3998, 3464, 2785, 2827, 2310, and 2332 dpm for 0, 0.5, 2, 8, 32, 125, and 250 ,g/mL, respectively. In the second experiment, PC-3 cells were cultured for 48 hr with 50, 100 and 200 ,g/mL of rOvUS or ovalbumin. Cells were then fixed and apoptotic cells identified using the TUNEL assay to detect DNA fragmentation. There was no effect of OvUS at any concentration tested on the percent of cells that were apoptotic. Percent apoptosis was 1.3% for control cells, 3.8%, 4.8% and 2% for cells cultured with 50, 100 and 200 ,g/mL rOvUS, and 2% for cells cultured with 200 ,g/mL ovalbumin. Results confirm that OvUS inhibits proliferation of PC-3 cells and indicate that inhibition does not involve induction of apoptosis. Further experiments are warranted to elucidate the anti-proliferative mechanism of action of OvUS. [source] | ||||||||||||||||||||||||||||||||||||||||