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)

The application of hyperthermia to the treatment of neoplastic disease has focused on solid tumors. Since the hyperthermic sensitivity of human B-cell lymphoma cells is not known, we have examined the effect of hyperthermia on the growth of B-cell lymphoma cell lines (Raji and Daudi) in vitro to evaluate the ability to purge tumor cells from normal bone marrow by heat, utilizing a limiting-dilution assay to measure log depletion of tumor cells in a 20-fold excess of normal bone marrow. When exposed at 42 degrees C and 43 degrees C for 120 min, both clonogenic Raji and Daudi cells were dramatically decreased (a 4- to 6-log reduction) with exposure time, while leaving over half of the normal granulocyte-macrophage progenitor cells surviving at 42 degrees C and 10% at 43 degrees C. This high level of lymphoma-cell depletion by heat correlated with that obtained in immunologic and pharmacologic studies. These results suggest that in vitro hyperthermia might be applied effectively for the elimination of residual lymphoma cells in autologous marrow grafts before autologous bone marrow transplantation in B-cell non-Hodgkin's lymphoma.
 ...
PMID:A simple elimination of clonogenic tumor cells from human bone marrow in vitro by heat: its application to autologous bone marrow transplantation for B-cell lymphoma. 163 79

Three predominantly CD8+ CTL lines, TIL 501, TIL 620, and TIL 660, were generated from three HLA-A2+ melanoma patients by culturing tumor-infiltrating lymphocytes in 1000 U/ml IL-2. These tumor-infiltrating lymphocytes lysed 12 of 18 HLA-A2+ autologous and allogeneic melanomas, but none of 20 HLA-A2-negative melanomas. They also did not lyse the MHC class I negative lymphoma-leukemia cell lines, Daudi, K562, or HLA-A2+ non-melanoma cell lines including PHA or Con A-induced lymphoblast, fibroblast, EBV-transformed B cell, Burkitt's B cell lymphoma, and colon cancer cell lines. Autologous and allogeneic melanoma lysis was inhibited by anti-CD3, by anti-MHC class I, and by anti-HLA-A2 mAb, indicating recognition of shared tumor Ag among melanoma cell lines in a TCR-dependent, HLA-A2-restricted manner. Six HLA-A2-negative melanoma cell lines obtained from five HLA-A2-negative patients were co-transfected with the HLA-A2.1 gene and pSV2neo. All 17 cloned transfectants expressing cell surface HLA-A2 molecules, but none of 12 transfectants lacking HLA-A2 expression, were lysed by these three HLA-A2-restricted, melanoma-specific CTL. Lysis of the HLA-A2+ transfectants was inhibited by anti-CD3, by anti-MHC class I, and by anti-HLA-A2 mAb, indicating recognition of shared tumor Ag on transfectants in a TCR-dependent, HLA-A2-restricted manner. These results identify the HLA-A2.1 molecule as an Ag-presenting molecule for melanoma Ag. They also suggest that common melanoma Ag are expressed among melanoma patients regardless of HLA type. These findings have implications for the development of melanoma vaccines that would induce antitumor T cell responses.
 ...
PMID:Shared human melanoma antigens. Recognition by tumor-infiltrating lymphocytes in HLA-A2.1-transfected melanomas. 172 79

The two monoclonal antibodies (mAb), L6 (anti-carcinoma), and 1F5 [anti-(B-cell-lymphoma)], were chemically linked to the enzyme penicillin-V amidase (PVA), which hydrolyzes phenoxyacetamides, to explore the potential of using mAb-enzyme conjugates for the localization of chemotherapeutic drugs at tumor cells. The phenoxyacetamide derivatives of doxorubicin and melphalan were prepared, yielding the less toxic amides, doxorubicin-N-p-hydroxyphenoxyacetamide (DPO) and melphalan-N-p-hydroxyphenoxyacetamide (MelPO). These were hydrolyzed by PVA to doxorubicin and melphalan respectively. In vitro studies with the L6-positive lung carcinoma cell line, H2981, and the 1F5-positive B-cell lymphoma line, Daudi, showed that DPO was 80-fold less toxic to H2981 cells and 20-fold less toxic to Daudi cells than doxorubicin, and its toxicity was substantially increased when the H2981 cells were pretreated with L6-PVA or the Daudi cells were pretreated with 1F5-PVA. The cytotoxic effect was antigen-specific, since only the binding mAb-enzyme conjugate increased the cytotoxicity of the prodrug. MelPO was more than 1000-fold less toxic than melphalan to H2981 cells and more than 100-fold less toxic than melphalan to Daudi cells. Pretreatment with the mAb-PVA conjugates did not enhance the toxicity of MelPO in either cell line, because PVA hydrolyzes the phenoxyacetamide bond of MelPO too slowly to generate a toxic level of melphalan.
 ...
PMID:Antibody-penicillin-V-amidase conjugates kill antigen-positive tumor cells when combined with doxorubicin phenoxyacetamide. 211 31

A new promoter of the human c-myc gene called P0, with multiple RNA start sites, was mapped over 500 bases upstream of the two previously identified promoters, P1 and P2. Sequencing full-length cDNA clones of P0 RNAs revealed two open reading frames upstream of that for the P64c-myc protein. P0 RNA is located on polyribosomes and released by puromycin, indicating that it functions as an mRNA. In vitro translation of RNA synthesized from the cloned cDNAs predicts that P0 transcripts are translated into a novel 12.5-kilodalton protein corresponding to the first open reading frame. The regulation of P0 RNA was studied in the B-cell lymphoma cell line Manca, in which only the translocated c-myc allele lacking exon 1 was thought to be active. However, we found that P0 transcription and the DNase I-hypersensitive site associated with this promoter persist on the untranslocated allele, even though P1/P2 transcription as measured by a nuclear runoff assay was repressed. These results suggest that allelic exclusion of c-myc expression in this B-cell lymphoma is caused by a repression of transcription which is specific to the P1/P2 promoters. We previously reported a block to elongation of transcription near the 3' end of exon 1 in the wild-type c-myc gene, which results in an excess of exon 1 over exon 2 transcription (5a). In contrast, we found that in the Daudi B-cell lymphoma, which retains exon 1 in the active allele, equimolar transcription of exons 1 and 2 occurs. This result suggests a model for the activation of c-myc in B-cell lymphomas.
 ...
PMID:Novel promoter upstream of the human c-myc gene and regulation of c-myc expression in B-cell lymphomas. 354 May 91

We have studied the potential use of immunotoxins (ITs) for therapeutic treatment of human tumors in an experimental model of human neoplasia. We tested intact ricin IT for its antitumor activity against established tumors. CEM, a human T-cell leukemia line expressing an Mr 67,000 cell surface antigen, and Daudi, a human B-cell lymphoma line which does not express the antigen, were found to be consistently tumorigenic in nude mice. ITs were synthesized using T101, a high-affinity monoclonal antibody reacting with the Mr 67,000 protein determinant and intact ricin. We have shown for the first time that established CEM solid tumors in nude mice will regress following intratumoral injection of T101-ricin IT, while Daudi tumors will not. Selective activity of T101-ricin is dependent on systemic i.v. administration of lactose and local intratumoral injection of the T101-ricin IT with lactose. Intact ricin ITs require the presence of lactose to block native ricin binding and render them antigen specific when linked to monoclonal antibody. Killing of target was cell specific since (a) nonspecific (irrelevant) ITs did not cause the regression of CEM tumors, and (b) injection of large amounts of free T101 antibody prior to T101-ricin IT blocked antitumor activity. Selectivity was not absolute, since regression occurred in one of six animals given irrelevant IT, and blocking was observed in two of four mice. Intratumoral IT treatment with 1 or 2 micrograms of T101-ricin IT plus lactose was not harmful to mice in contrast to intratumoral ricin treatment, which killed all treated tumor-bearing mice at a dose of 0.3 micrograms. Without i.v. injection of lactose, intratumoral injection of T101-ricin IT was also effective in eliminating established tumors. However, this treatment did not result in the selective elimination of tumor, since Daudi tumors also regressed following T101-ricin IT treatment. IT, made with ricin A chain only (T101-A chain IT), was also tested against established CEM tumors. We found that high dosages of T101-A chain IT did not destroy CEM tumors when injected intratumorally, even in the presence of activating agents such as NH4Cl or the carboxylic ionophore X-537 A. In contrast, in vitro experiments demonstrated that T101-A chain IT plus activating agents had potent and selective cytotoxic effect against CEM cells. We conclude that ITs are specifically toxic to established tumors. Although selectivity is not absolute, ITs exhibit potential as a new class of antitumor reagents.
 ...
PMID:Cytotoxic effect of anti-Mr 67,000 protein immunotoxins on human tumors in a nude mouse model. 397 76

The human homologue of 4-1BB (H4-1BB) cDNA was isolated from PMA plus ionomycin-treated human peripheral T-cell cDNA libraries. The amino acid sequence deduced from the nucleotide sequence showed that the protein is composed of 255 amino acids with 2 potential N-linked glycosylation sites. The molecular weight of its protein backbone is calculated to be 27 kDa. The H4-1BB contains features such as signal sequence and transmembrane domain, indicating that it is a receptor protein. This protein showed 60% identity of amino acid sequence to mouse 4-1BB. In the cytoplasmic domain there are 5 regions of amino acid sequences conserved from mouse to human, indicating that these residues might be important in the 4-1BB function. H4-1BB mRNA was detected in unstimulated peripheral blood T cells and was inducible in T-cell lines such as Jurkat and CEM. H4-1BB-AP, a fusion protein between the H4-1BB extracellular domain and alkaline phosphatase, was used to identify the ligand for the H4-1BB. Although the H4-1BB ligand was detected in both T and B cells of human peripheral blood, the ligand was preferentially expressed in primary B cells and B-cell lines. Daudi, a B-cell lymphoma, was one of the B-cell lines that carried a higher number of ligands. Scatchard analysis showed that the Kd = 1.4 x 10(9) M and the number of ligands in Daudi cell was 4.2 x 10(3).
 ...
PMID:Characterization of human homologue of 4-1BB and its ligand. 762 90

We have examined the antitumor activity of murine interleukin 4 (IL-4) on development of a human B-cell lymphoma (Daudi) in severe combined immunodeficient (SCID) mice. The progression of Daudi cells in SCID mice was followed by histological staining and by flow cytometric analysis of CD20+ cells in spleen, liver, bone marrow, and kidneys. By day 35, CD20+ Daudi cells populate the majority of space in the bone marrow and kidney in vehicle-treated mice. Mice receiving i.p. injections of IL-4, commencing 7 or 14 days after tumor inoculation, exhibit a reduction in tumor burden as well as a decrease in CD20+ cells in both compartments. The antitumor activity of IL-4 does not appear to be due to an antiproliferative effect, since the cytokine does not alter the growth of Daudi cells in vitro, nor does it correlate with any marked cellular infiltrate in tumor-bearing tissues. In 51Cr-release assays, we observed that splenocytes from IL-4-treated mice were capable of lysing YAC-1 but not Daudi cell targets. Our findings demonstrate that: (a) systemic administration of IL-4 retards dissemination of a human B-cell lymphoma in SCID mice; and (b) antitumor activity elicited by IL-4 may not involve a direct effect on proliferation of Daudi cells or on the induction of cytolytic activity.
 ...
PMID:Interleukin 4 retards dissemination of a human B-cell lymphoma in severe combined immunodeficient mice. 764 Nov 77

A panel of bispecific F(ab')2 antibodies (BsAb) have been constructed for delivering the ribosome-inactivating protein saporin to human B cell lymphoma. Each derivative was prepared with specificity for saporin and CD19, CD22, CD37, or immunoglobulin. In vitro studies measuring inhibition of [3H]leucine uptake by cultured Daudi and Raji cells demonstrated that, despite all BsAb capturing saporin on the cell surface, BsAb targeting through CD22 were far more cytotoxic than those functioning via CD19, CD37, or surface immunoglobulin. This exceptional activity of the CD22-specific BsAb appears to derive from its ability to deliver and accumulate saporin inside the target cells. Further studies showed that four CD22-specific BsAb all performed with equal potency and were able to increase saporin toxicity (50% inhibitory concentration) up to 1000-fold, from 2 x 10(-7) M to 2 x 10(-10) M. Pairs of anti-CD22 BsAb which recognized different nonblocking epitopes on the saporin molecule were able to bind saporin more avidly to the target cell and, as a consequence, increased cytotoxicity by at least an additional 10-fold, resulting in 50% inhibitory concentration for protein synthesis of 2 x 10(-11) M. These results suggest that selected combinations of BsAb which bind cooperatively to a toxin and the cell surface may provide an efficient way of delivering toxins to unwanted cells in patients.
 ...
PMID:Delivery of saporin to human B-cell lymphoma using bispecific antibody: targeting via CD22 but not CD19, CD37, or immunoglobulin results in efficient killing. 768 48

The epitopes Tn and sialosyl-Tn are expressed on erythrocytes of individuals with a very rare blood group, who often suffer from "Tn syndrome." We surveyed expression of Tn and sialosyl-Tn in normal blood cells, malignant transformed cells, and progenitor stem cells from bone marrow (BM). An anti-Tn antibody, IE3, and an anti-sialosyl-Tn antibody, TKH2, were used in this study. TKH2 reacted with erythroblasts, B cells, and a subset of CD4+ cells; but not with erythrocytes. Erythroblastic cell lines (K562, HEL, and UT7/EPO) and B-cell lines (Daudi, Raji, and B-cell lines transformed by Epstein-Barr virus) showed reactivity to TKH2. Similar results from the reactivity of TKH2 with transformed cells from leukemia patients and lymphoma patients were obtained; TKH2 reacted with blasts from erythroleukemia (M6; for 4 of 4 cases) and with lymphocytes from B-cell chronic lymphocytic leukemia (3 of 3), B-cell lymphoma (5 of 5), and CD4+ adult T-cell leukemia (4 of 4), but did not react with blasts from acute myeloid leukemia (M0 to M5; 0 of 22) or acute lymphoid leukemia (B-lymphoid leukemia, 0 of 11; T-lymphoid leukemia, 0 of 2; undifferentiated leukemia, 0 of 1). IE3 did not react with all of the tested cells. CD2-CD19-TKH2+ normal BM cells (BMC) contained blasts and various maturation stages of erythroblasts. The TKH2+ cells produced a large number of colony-forming unit-erythroid (CFU-E) colonies, whereas they produced a small number of burst-forming unit-erythroid colonies and CFU-granulocyte-macrophage colonies. CD34+ normal BMC did not express Tn and sialosyl-Tn. These findings suggest that sialosyl-Tn expresses in CFU-E to erythroblasts.
 ...
PMID:Expression of sialosyl-Tn in colony-forming unit-erythroid, erythroblasts, B cells, and a subset of CD4+ cells. 790 75

From a rat chondrosarcoma we isolated a cDNA that encodes a novel homeoprotein rDlx. The homeodomain of rDlx shows a high degree of sequence identity with those of Drosophila Distal-less, mouse Dlx, and Xenopus Xdll proteins. Northern hybridization of rDlx revealed a 1.4- to 1.6-kb RNA species in a rat chondrosarcoma and a cell line derived from this tumor and in mouse C3H10T1/2 cells, but no rDlx RNA was detected in mouse NIH3T3 fibroblasts, rat skin fibroblasts, mouse C2 myoblasts, mouse myeloma S194 cells, human B-cell lymphoma Daudi cells, or human acute myelocytic leukemia cells. RNase protection assays showed that rDlx transcripts were present at high levels in 14-day-old rat embryos, 18-day-old rat embryo skeletal tissues, and adult rat brain. rDlx RNAs were present at lower levels in newborn rat rib cartilage, 18-day-old rat embryo soft tissues, newborn rat skin, and adult rat heart. rDlx transcripts were not detected in adult rat liver, spleen, lung, kidney, testis, or skeletal muscle. In situ hybridization of rat embryos at different stages revealed that rDlx transcripts were present in otic vesicle, branchial arches, apical ectodermal ridge of limb bud, developing cartilages, perichondria of mature cartilages, mesenchymal cells of developing membranous bones, developing teeth, ganglionic eminence of the telencephalon, diencephalon, olfactory epithelia, and epidermis of the skin. rDlx RNAs were also detected in the developing parasympathetic mesenteric ganglia of the gastrointestinal tract. Hence, rDlx RNAs are mainly expressed in several neuronal tissues and developing skeletal tissues.
 ...
PMID:rDlx, a novel distal-less-like homeoprotein is expressed in developing cartilages and discrete neuronal tissues. 791 69


1 2 3 4 5 6 Next >>