Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0079731 (B-cell lymphoma)
 16,671 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Antibody (Ab) localization to Raji B-cell lymphoma xenografts in severe combined immunodeficient (SCID) mice was investigated using three Abs: anti-CD20; anti-CD147; and anti-MHC class II. These antigens are all high-density cell surface antigens, and the Abs are all considered to be slowly internalized and catabolized, with catabolism primarily due to the basal turnover rate of cell surface constituents. Unexpectedly, specific Ab uptake was demonstrated only when residualizing labels were used. The residualizing labels tested were 111In-benzyl-diethylenetriaminepentaacetic acid and [125I]iodo-dilactitol-tyramine, whereas the nonresidualizing label was a conventional iodine label. In contrast, in vitro experiments demonstrated very slow catabolism of the same Abs. These data strongly suggest that Ab catabolism is much more rapid in vivo than in vitro and has a strong impact on Ab accumulation in the tumor. If autologous human tumors are similar to these xenografts, then there should be a large advantage in the use of residualizing radiolabels for radioimmunotherapy.
 ...
PMID:Antibody localization to B-cell lymphoma xenografts in immunodeficient mice: importance of using residualizing radiolabels. 1217 95

Radioimmunotherapy consists of radiolabeled monoclonal antibodies for the treatment of malignancy. For more than a decade, radioimmunotherapy has shown great promise for the treatment of B-cell lymphoma. During the past decade, two products targeted to the CD20 antigen on B cells, iodine-131 tositumomab and yttrium-90 (90Y) ibritumomab tiuxetan, have been tested extensively in registration trials for potential licensing approval by the US Food and Drug Administration (FDA). Both products have produced response rates of 70% to 80% in low-grade and follicular lymphoma, and response rates of 50% to 60% in low-grade or follicular lymphoma that has transformed into an intermediate or high-grade lymphoma. Median duration of response to a single course of treatment has been about 1 year, with complete remission rates in one quarter to one third of patients. In February, 2002, 90Y ibritumomab tiuxetan was formally approved by the FDA for the treatment of relapsed or refractory low-grade, follicular, or transformed B-cell lymphoma, including rituximab-refractory transformed lymphoma, thus becoming the first radioimmunotherapeutic agent approved by the agency. The product became available for commercial use in April, 2002. Clinical trials will determine how radioimmunotherapy will be integrated into the treatment of lymphoma.
 ...
PMID:Radioimmunotherapy of relapsed or refractory low-grade, follicular, or transformed B-cell non-Hodgkin's lymphoma. 1290 Nov 52

Radioimmunotherapy (RIT) treatment for lymphoma is a novel targeted therapeutic approach. Several years of development of radioimmunotherapeutic compounds came to fruition in February of 2002 when the US Food and Drug Administration (FDA) approved yttrium 90 ((90)Y)-ibritumomab tiuxetan ((90)Y-IT) for the treatment of relapsed or refractory, low-grade, or transformed B-cell lymphoma. (90)Y-IT uses a monoclonal anti-CD20 antibody to deliver beta-emitting (90)Y to the malignant B cells. Clinical trials have demonstrated its efficacy, which is largely independent of the intrinsic activity of the anti-CD20 antibody. A similar anti-CD20 radiotherapeutic compound, iodine 131 ((131)I)-tositumomab ((131)I-T), is also under consideration for approval. The advantages of increased efficacy compared to the native antibody are gained at the expense of myelotoxicity, which is dose-limiting but reversible. Other radioimmunoconjugates (RIC), including products for Hodgkin's lymphoma, are in earlier stages of development. Studies exploring expanded applications of RIT are under way. RIT has been shown to be an effective and clinically relevant complementary therapeutic approach for patients with lymphoma.
 ...
PMID:Radioimmunotherapy for non-Hodgkin's lymphoma. 1293 22

The characterization of genetic aberrations in paraffin-embedded tumor material is impaired by contaminating normal cells. In the present study on the genetic causes of loss of HLA expression in diffuse large B-cell lymphoma (DLBCL), we compared the efficacy of microdissection with flow cytometric sorting of tumor cells. Single-cell suspensions from paraffin-embedded material of 5 DLBCL cases were stained for CD79a and DNA content (propidium iodide). Fluorescent in situ hybridization (FISH) using HLA class II and chromosome 6 centromeric probes and loss of heterozygosity (LOH) analysis with 5 HLA-specific microsatellite markers were performed on microdissected and flow cytometry-sorted fractions. FISH confirmed considerable enrichment of the samples after flow cytometric sorting and disclosed tumor heterogeneity in 4 cases. Moreover, lymphomas with a so-called zebra LOH pattern in the microdissected material showed unambiguous LOH after flow cytometric sorting, revealing in 1 case a biologically relevant hemizygous deletion in the HLA region.
 ...
PMID:Flow cytometric sorting of paraffin-embedded tumor tissues considerably improves molecular genetic analysis. 1450 96

Waldenstrom's macroglobulinemia is an indolent B-cell malignancy that is characterized by high levels of IgM paraprotein production and is incurable with standard chemotherapy. Iodine 131I-Tositumomab (iodine-131-labeled murine anti-CD20 monoclonal antibody; Bexxar) is a novel radioimmunotherapeutic agent that has a high response rate in relapsed or chemotherapy refractory, CD20-positive, low grade or transformed B-cell non-Hodgkin's lymphomas. There are no data on the use of radioimmunotherapy in Waldenstrom's macroglobulinemia. We report a patient with Waldenstrom's macroglobulinemia with transformation to a large B-cell lymphoma, who was treated successfully with iodine 131I-tositumomab. The patient had a complete response to the treatment, including disappearance of any detectable IgM paraprotein. This case report demonstrates the potential for radioimmunotherapy in CD20 positive B-cell malignancies.
 ...
PMID:Use of iodine 131I-tositumomab radioimmunotherapy in a patient with Waldenstrom's macroglobulinemia. 1516 Sep 23

In the last years monoclonal antibodies directed against B-cell associated epitopes have enriched our armentarium of therapeutic strategies against malignant B-cell lymphoma. Monoclonal antibodies are characterized by a different mode of action compared to chemotherapy, thereby opening new avenues in lymphoma treatment. These monoclonal antibodies can exert their anti-lymphoma activity directly by an intrinsic cytotoxic effect or indirectly as a carrier of cytotoxic drugs or radioisotopes. Rituximab, an anti-CD20 monoclonal antibody, was proven to be highly active in indolent as well as aggressive lymphoma, in particular when combined with chemotherapy. The anti-CD52 antibody alemtuzumab was shown to induce remissions in high risk CLL. Furthermore, clinical trials have demonstrated promising activity of monoclonal antibodies conjugated to radioisotopes such as the (131)iodine anti-CD20 antibody tositumomab or the (90)yttrium anti-CD20 antibody ibritumomab tiuxetan.
 ...
PMID:[Monoclonal antibody treatment of malignant lymphoma]. 1551 23

Interleukin (IL)-5 plays an important role in maintaining the survival of eosinophils via the specific alpha-subunit of its receptor. Apoptosis, a form of programmed cell death, is thought to represent a mechanism that promotes the resolution of eosinophilic inflammation in asthma. The aim of our present study is to investigate whether IL-5 acts in an autocrine fashion on eosinophil apoptosis in asthmatics. Immunoreactivities of intracellular IL-5 and IL-5 receptor alpha-subunit (Ralpha) were detected uniquely on the eosinophils. The magnitude of IL-5 and IL-5 Ralpha expression on eosinophils was significantly higher in asthmatics than that of normal subjects (p<0.05) determined by flow cytometry. Apoptosis of eosinophils was measured by the propidium iodide staining method and DNA ladder. The percent of apoptotic eosinophils from asthmatics was significantly increased by coincubation with anti-hIL-5 Ralpha Ab (0.1, 0.5, and 2.5 microg/mL) for 1, 2, or 16 hours than was those of corresponding controls (p<0.05, n=8). However, there was no significant effect of anti-hIL-5 Ralpha Ab on eosinophil apoptosis in normal subjects. Furthermore, the expression of B-cell lymphoma-2 (Bcl-2) proteins was significantly inhibited by the anti-hIL-5 Ralpha Ab or antisense IL-5 oligonucleotides in asthmatics (p<0.05, n=8), but there was no significant change in eosinophils from normal subjects. This study demonstrates that eosinophils from asthmatics release IL-5 in an autocrine fashion to act on their own IL-5 receptors in prevention of apoptosis through the upregulation of Bcl-2 expression.
 ...
PMID:Eosinophils from asthmatics release IL-5 in an autocrine fashion to prevent apoptosis through upregulation of Bcl-2 expression. 1603 15

Radioimmunotherapy involves a form of biologically targeted radiopharmaceutical treatment in which a radioactive isotope (typically a short-range, high-energy beta-emitter) is chemically bound to a target-specific monoclonal antibody or fragment. Thus, these radioimmunoconjugates combine the exquisite targeting specificity of the humoral immune system with the known cancer-killing power of high-energy radiotherapy. To date, two radioimmunotherapy agents have been fully approved for commercial use: 90Yttrium ibritumomab tiuxetan and (131)Iodine tositumomab. Both compounds target the CD20 surface molecule found on normal and malignant B cells, and both are medically indicated for the treatment of indolent B-cell lymphoma and related conditions. Clinical results are excellent (20-40% complete response rates and 60-80% overall response rates) and toxicity is typically quite mild. Current research is now attempting to both explore the biology of these compounds and to expand the spectrum of CD20+ diseases that could be treated using either or both of these active agents. Concurrently, work is in progress to achieve the same excellent clinical results using antibodies specific for other, more common epithelial tumors. This work is at an earlier stage than the lymphoma work, partly due to the high innate radiosensitivity of the lymphoid system. Thus, various enhancement methodologies are being explored to increase clinical response rates for these solid tumors, and a number of solid tumor RIT agents are now in early-stage clinical trials. The most likely pattern of use for this field in the next 5 years will probably involve combination or sequential regimens incorporating both radioimmunotherapy and more conventional chemotherapy or external radiotherapy.
 ...
PMID:Review of clinical radioimmunotherapy. 1650 61

We have recently shown that cannabinoids induce growth inhibition and apoptosis in mantle cell lymphoma (MCL), a malignant B-cell lymphoma that expresses high levels of cannabinoid receptor types 1 and 2 (CB(1) and CB(2)). In the current study, the role of each receptor and the signal transduction triggered by receptor ligation were investigated. Induction of apoptosis after treatment with the synthetic agonists R(+)-methanandamide [R(+)-MA] and Win55,212-2 (Win55; (R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl) pyrrolo-[1,2,3-d,e]-1,4-benzoxazin-6-yl]-1-naphthalenyl-methanone) was dependent on both cannabinoid receptors, because pretreatment with N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboximide hydrochloride (SR141716A) and N-((1S)-endo-1,3,3-trimethyl bicyclo heptan-2-yl]-5-(4-chloro-3-methylphenyl)-1-(4-methylbenzyl)-pyrazole-3-carboxamide) (SR144528), specific antagonists to CB(1) and CB(2), respectively, abrogated caspase-3 activity. Preincubation with the inhibitors 4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)1H-imidazole (SB203580) and 4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)-1H-imidazole (SB202190) showed that phosphorylation of MAPK p38 was implicated in the signal transduction leading to apoptosis. Treatment with R(+)-MA and Win55 was associated with accumulation of ceramide, and pharmacological inhibition of ceramide synthesis de novo prevented both p38 activation and mitochondria depolarization assessed by binding of 3,3'-dihexyloxacarbocyanine iodide (DiOC(6)). In contrast, the pancaspase inhibitor z-Val-Ala-Asp(Ome)-CH(2)F (z-VAD-FMK) did not protect the mitochondrial integrity. Taken together, these results suggest that concurrent ligation of CB(1) and CB(2) with either R(+)-MA or Win55 induces apoptosis via a sequence of events in MCL cells: accumulation of ceramide, phosphorylation of p38, depolarization of the mitochondrial membrane, and caspase activation. Although induction of apoptosis was observed in both MCL cell lines and primary MCL, normal B cells remained unaffected. The present data suggest that targeting CB(1)/CB(2) may have therapeutic potential for the treatment of mantle cell lymphoma.
 ...
PMID:Cannabinoid receptor-mediated apoptosis induced by R(+)-methanandamide and Win55,212-2 is associated with ceramide accumulation and p38 activation in mantle cell lymphoma. 1693 28

Tositumomab/iodine-131 tositumomab (Bexxar) and ibritumomab tiuxetan (Zevalin) are radioimmunoconjugates targeting the CD20 antigen. Both agents are approved in the United States for use in relapsed or refractory, indolent or transformed, B-cell lymphoma. These agents are well tolerated and have the highest levels of single-agent activity observed in these histologies. This review will summarize the key trials that led to approval of both I-131 tositumomab and ibritumomab tiuxetan, and then focus on four novel therapeutic concepts in radioimmunotherapy: retreatment, therapy of de novo indolent lymphoma, therapy of aggressive histologies, and incorporation in high-dose therapy programs utilizing autologous stem cell support.
 ...
PMID:Novel concepts in radioimmunotherapy for non-Hodgkin's lymphoma. 1739 83


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>