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Query: UMLS:C0019829 (Hodgkin's disease)
 30,247 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

As there are very few reproducible animal models without conditioning available for the study of human B-cell-type Hodgkin's lymphoma (HL), we investigated the ability of HL cells to induce tumors using novel NOD/SCID/gammac(null) (NOG) mice. Four human Epstein-Barr virus-negative cell lines (KM-H2 and L428 originated from B cells, L540 and HDLM2 originated from T cells) were inoculated either subcutaneously in the postauricular region or intravenously in the tail of unmanipulated NOG mice. All cell lines successfully engrafted and produced tumors with infiltration of cells in various organs of all mice. Tumor cells had classical histomorphology as well as expression patterns of the tumor marker CD30, which is a cell surface antigen expressed on HL. Tumor progression in mice inoculated with B-cell-type, but not T-cell-type, HL cells correlated with an elevation in serum human interleukin-6 levels. Tumor cells from the mice also retained strong nuclear factor (NF)-kappaB DNA binding activity, and the induced NF-kappaB components were indistinguishable from those cultured in vitro. The reproducible growth behavior and preservation of characteristic features of both B-cell-type and T-cell-type HL in the mice suggest that this new xenotransplant model can provide a unique opportunity to understand and investigate the mechanism of pathogenesis and malignant cell growth, and to develop novel anticancer therapies.
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PMID:Hodgkin's lymphoma cells are efficiently engrafted and tumor marker CD30 is expressed with constitutive nuclear factor-kappaB activity in unconditioned NOD/SCID/gammac(null) mice. 1610 27

The aim of this pilot study was to determine VEGF serum levels (S-VEGF) at diagnosis and at restaging in children diagnosed with cancer, and to investigate whether this parameter provides prognostic information for remission after induction therapy and response to treatment. S-VEGF levels of 35 consecutive pediatric patients with various types of cancer were assayed at diagnosis and at restaging. Levels of VEGF were determined using a commercially available ELISA anti-human VEGF immunoassay kit. Thirty-one children went into complete remission or had a very good partial response to first-line therapy; 4 patients developed tumor progression. At diagnosis average S-VEGF level was 495 pg/mL (range, 0.89--2220 pg/mL) and at restaging it decreased to 118.36 pg/mL (range, 7.44--487 pg/mL). (p=.0039). The 4 patients with tumor progression had increased S-VEGF levels at restaging. The comparison between the levels of S-VEGF at diagnosis and at restaging showed a significant difference for the patients who responded to treatment with decreased S-VEGF and the patients who developed tumor progression with increased S-VEGF (p=.0019). One child with metastatic Ewing sarcoma developed progressive disease after several weeks, with significantly progressively higher S-VEGF levels. One child with Hodgkin disease, who had a higher level at first restaging and developed progressive disease, responded to reinduction therapy and had a significantly lower level at the second restaging. The child with metastatic hepatoblastoma responded to first-line chemotherapy with concomitant decrease in S-VEGF and alpha-fetoprotein levels, but developed local recurrence with elevation in both parameters. Changes in S-VEGF levels correlated with response to treatment for most of the children diagnosed with cancer. This provides a rationale for exploring clinical interest in S-VEGF measurements of a larger group of children with malignancies, and using the test for clinical trials of antiangiogenic therapies.
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PMID:Serum vascular endothelial growth factor as a significant marker of treatment response in pediatric malignancies. 1616 18

Nonmyeloablative allogeneic transplantation provides a valuable therapeutic option for patients with relapsed non-Hodgkin lymphomas, particularly those that have recurred after autologous transplantation. However, the absence of an intensive conditioning regimen renders this approach less effective for patients with aggressive or bulky lymphoma because rapid tumor growth may outpace the evolution of the graft-versus-lymphoma effect. Radioimmunotherapy provides an attractive, minimally toxic modality to safely prevent early progression of B-cell lymphomas and induce remissions without incurring the risks of traditional intensive therapy. This approach provides a time window during which a robust graft-versus-lymphoma effect may be established before tumor progression, thereby providing more effective long-term disease control. The rationale for incorporation of radioimmunotherapy into reduced intensity allogeneic transplantation regimens for non-Hodgkin lymphoma is discussed, as are current study designs, preliminary results, and future directions.
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PMID:Improving the efficacy of reduced intensity allogeneic transplantation for lymphoma using radioimmunotherapy. 1678 58

Recombinant interleukin-2 (rIL-2) is a pleiotropic cytokine that activates select immune effector cell responses associated with antitumor activity, including antibody-dependent cellular cytotoxicity (ADCC). Rituximab is an anti-CD20 monoclonal antibody that activates ADCC in non-Hodgkin lymphoma (NHL). The ability of rIL-2 to augment rituximab-dependent tumor responses was investigated. The efficacy of rIL-2 in combination with rituximab was evaluated in 2 NHL tumor xenograft models: the CD20hi, rituximab-sensitive, low-grade Daudi model and the CD20lo, aggressive, rituximab-resistant Namalwa model. Combination of rIL-2 plus rituximab was synergistic in a rituximab-sensitive Daudi tumor model, as evidenced by significant tumor regressions and increased time to tumor progression, compared with rIL-2 and rituximab single agents. In contrast, rituximab-resistant Namalwa tumors were responsive to single-agent rIL-2 and showed an increased response when combined with rituximab. Using in vitro killing assays, rIL-2 was shown to enhance activity of rituximab by activating ADCC and lymphokine-activated killer activity. Additionally, the activity of rIL-2 plus rituximab F(ab')2 was similar to that of rIL-2 alone, indicating a critical role for immunoglobulin G1 Fc-FcgammaR-effector responses in mediating ADCC. Antiproliferative and apoptotic tumor responses, along with an influx of immune effector cells, were observed by immunohistochemistry. Collectively, the data suggest that rIL-2 mediates potent tumoricidal activity against NHL tumors, in part, through activation and trafficking of monocytes and natural killer cells to tumors. These data support the mechanistic and therapeutic rationale for combination of rIL-2 with rituximab in NHL clinical trials and for single-agent rIL-2 in rituximab-resistant NHL patients.
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PMID:Recombinant interleukin-2 significantly augments activity of rituximab in human tumor xenograft models of B-cell non-Hodgkin lymphoma. 1719 84

Most human lymphomas originate from transformed germinal center (GC) B lymphocytes. While activating mutations and translocations of MYC, BCL2 and BCL6 promote specific GC lymphoma subtypes, other genetic and epigenetic modifications that contribute to malignant progression in the GC remain poorly defined. Recently, aberrant expression of the TCL1 proto-oncogene was identified in major GC lymphoma subtypes. TCL1 transgenic mice offer unique models of both aggressive GC and marginal zone B-cell lymphomas, further supporting a role for TCL1 in B-cell transformation. Here, restriction landmark genomic scanning was employed to discover tumor-associated epigenetic alterations in malignant GC and marginal zone B-cells in TCL1 transgenic mice. Multiple genes were identified that underwent DNA hypermethylation and decreased expression in TCL1 transgenic tumors. Further, we identified a secreted isoform of EPHA7, a member of the Eph family of receptor tyrosine kinases that are able to influence tumor invasiveness, metastasis and neovascularization. EPHA7 was hypermethylated and repressed in both mouse and human GC B-cell non-Hodgkin lymphomas, with the potential to influence tumor progression and spread. These data provide the first set of hypermethylated genes with the potential to complement TCL1-mediated GC B-cell transformation and spread.
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PMID:Global DNA methylation profiling reveals silencing of a secreted form of Epha7 in mouse and human germinal center B-cell lymphomas. 1726 20

Mantle cell lymphoma (MCL) is one of the most frequent of the newly recognized non-Hodgkin's lymphomas. The major problem of MCL therapy is the occurrence of relapse and subsequent resistance to chemotherapy and immunotherapy in virtually all cases. Here, we show that one injection of anti-human transferrin receptor (TfR) monoclonal antibody A24 totally prevented xenografted MCL tumor establishment in nude mice. It also delayed and inhibited tumor progression of established tumors, prolonging mice survival. In vitro, A24 induced up to 85% reduction of MCL cell proliferation (IC(50) = 3.75 nmol/L) independently of antibody aggregation, complement-dependent or antibody-dependent cell-mediated cytotoxicity. A24 induced MCL cell apoptosis through caspase-3 and caspase-9 activation, either alone or synergistically with chemotherapeutic agents. A24 induced TfR endocytosis via the clathrin adaptor protein-2 complex pathway followed by transport to lysosomal compartments. Therefore, A24-based therapies alone or in association with classic chemotherapies could provide a new alternative strategy against MCL, particularly in relapsing cases.
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PMID:Prevention of mantle lymphoma tumor establishment by routing transferrin receptor toward lysosomal compartments. 1728 49

Survivin (S) is a member of inhibitor of apoptosis family (IAP) and is expressed in the majority of malignant tumors but undetectable in normal differentiated adult tissues. S is an encouraging target for cancer therapy. TSP-1 is a multifunctional protein regulating cell growth, motility and apoptosis in both physiological and pathological conditions. The role of TSP-1 in cancer progression remains controversial. We aimed to determine the pathogenetic and prognostic role of TSP-1 and S in non-Hodgkin's lymphomas (NHL). S and TSP-1 expressions were looked for in 177 cases with NHL. S was found to be positive in 94 of the cases (53%). TSP-1 was found to be positive in 31 of the cases (17.5%). There was a strong association between S and TSP-1 and also aggressive histology with S and TSP-1. The overall survival (OS) times were longer in cases without S expression than cases with S expression (p=0.0514). Although the OS was shorter in TSP-1 expressing cases as compared with TSP-1 (-) cases, difference was not significant (p=0.2428). In conclusion, S and TSP-1 expressions were detected in 53 and 17.5% of the cases with NHL, and are associated with aggressive histology and shorter OS.
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PMID:Thrombospondin-1 (TSP-1) and Survivin (S) expression in non-Hogkin's lymphomas. 1770 82

Hodgkin Lymphoma (HL) has become one of the most curable cancers, even in adulthood, through continuous improvement of therapeutic options and their verification by large multicenter trials. Today more than 95% of patients with HL in early stages and in advanced stages 85-90% can be cured. Nevertheless, these good results are threatened by treatment associated toxicities such as infertility, cardiopulmonary toxicity and secondary malignancies. It is therefore the aim of future trial generations both to maintain the excellent treatment results and to minimize late effects. In 1964 for the first time deVita et al. described the MOPP polychempotherapy for patients with advanced HL which led to cure rates in more than 50%. Around ten years later Bonadonna et al. established the non cross resistant alternative regime to MOPP, ABVD which nowadays is accepted as "gold standard" for the treatment of advanced HL. MOPP and/or ABVD and furthermore the alternating MOPP/ABVD or the MOPP/ABV hybrid with and without the help of consolidative radiation resulted in around 70% long term survival rates, 30-40% of patients experienced tumor progression or relapses within 5 years. This led the German Hodgkin Study Group (GHSG) [Diehl V, Franklin J, Pfreundschuh M, Lathan B, Paulus U, Hasenclever D, et al. Standard and increased-dose BEACOPP chemotherapy compared with COPP-ABVD for advanced Hodgkin's disease. N Engl J Med 2003; 348: 2386-95] to improve the efficacy of COPP/ABVD by time- and dose-intensification, omission of Velban and Dacarbazin and adding Etoposide resulting in the BEACOPP principle. From the initial pilot studies in 1992 three trial generations, HD9, HD12, HD15, have now established this principle as one of the most effective chemotherapy regimen in advanced HL. We certainly hope that it will not last another 20 years to establish the BEACOPP regimen as an attractive curative treatment option for at least the high risk cohorts of HL.
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PMID:Will BEACOPP be the standard for high risk Hodgkin lymphoma patients in advanced stages? 1771 96

Mina53 (mina) was identified as a gene, which is directly induced by the oncogene c-myc. Elevated expression of Mina53 protein was found in >80% of colon cancer and esophageal squamous cell carcinoma (ESCC). Patients with high expression of Mina53 had shorter survival, suggesting the prognostic usefulness of Mina53. We studied Mina53 expression in lymphoma subtypes to examine its diagnostic significance and its possible role in lymphoma-genesis. Surgical cases of 28 lymphoma and 4 non-neoplastic tissues were stained immunochemically using anti-Mina53 monoclonal antibody. Mina53 expression correlated well with c-Myc expression in lymphoma, suggesting that c-Myc is a controlling factor for mina53 expression also in lymphomas. Although the expression of Mina53 as well as c-Myc was less frequent in lymphoma compared with those of colon and ESCC, increased expression of Mina53 was found in Burkitt-like lymphoma (1/1), Hodgkin's lymphoma (3/5), diffuse large B cell lymphoma (DLBCL) (5/13), lymphomas with a transition from follicular to DLBCL (1/2), with none in follicular (0/4) and T cell lymphoma (0/3). Analyses of the data suggested that Mina53 was frequently expressed in aggressive types of B cell lymphoma. To get more information about the expression of Mina53 in DLBCL, which most frequently occurs among lymphomas, we analyzed the expression of Mina53 in another 21 DLBCL specimens, which were in more advanced stages than those described above. The expression level of Mina53 correlated to the international prognostic index (IPI) values with statistical significance (r=0.477, P=0.0275). Notably, in this group, Mina53 expression did not correlate with c-Myc expression, suggesting that other factor(s) besides c-Myc largely affect the expression of Mina53 in advanced DLBCL. These results suggest that although Mina53 expression is not prominent in lymphoma in general, it may be related to tumor progression of B cell lymphoma.
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PMID:Expression of Myc target gene mina53 in subtypes of human lymphoma. 1778 44

Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoid malignancy in adults, accounting for nearly 40% of all non-Hodgkin's lymphomas. As cell proliferation is essential for tumor growth, analysis of the cell cycle might give additional information on tumor progression. Although markers distinctive for cell-cycle regulation in DLBCL have been addressed, less attention has been paid to cyclin H in DLBCL with respect to its prognostic and potential therapeutic implications. Cyclin H occurs as a component of the cyclin H/Cdk 7/Mat 1 complex. Cyclin H is also a substrate of protein kinase 2, a ubiquitously expressed serine/threonine protein kinase required for cell viability and cell-cycle progression. We evaluated the expression of cyclin H by immunohistochemistry in 301 DLBCLs in a tissue microarray format. Validation was done by performing quantitative real-time polymerase chain reaction and Western blotting experiments for cyclin H. We studied the relationship between cyclin H expression in comparison to other cyclins (A, B1, D1, D3, and E) and the proliferation marker Ki-67. Reduced or absent cyclin H expression was seen in 14.5% of the DLBCL cases. Interestingly, reduced or absent cyclin H expression was correlated with lower expression of proliferation marker Ki-67 (P < .0001), cyclin B1 (P = .0001), cyclin D3 (P = .0007), and cyclin E (P < .0001). Reduced or absent cyclin H expression was significantly associated with poor overall survival, in both the univariate (P = .0286) and multivariate analysis with International Prognostic Index (P = .0180). Our study demonstrates the independent prognostic value of cyclin H expression in DLBCL and proposes its use as a prognostic marker.
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PMID:Reduced or absent cyclin H expression is an independent prognostic marker for poor outcome in diffuse large B-cell lymphoma. 1840 Feb 56


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