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)

Cultured tumor cell lines, tumor xenografts grown in athymic nude mice, and a murine experimental metastasis model were used to assess the in vitro and in vivo anti-tumor activity of the potent IMP dehydrogenase (IMPDH) inhibitor, mycophenolic acid (MPA), and its morpholinoethyl ester pro-drug, mycophenolate mofetil (MM). The growth of all the cell lines tested was inhibited by MPA in vitro, with EC50 values ranging from less than 0.1 microM to 3.9 microM. Mice were monitored for s.c. tumor outgrowth in the case of human tumor xenograft models or survival time for the murine experimental metastasis model. Treatment with MM p.o. was started 24 hr after tumor challenge or after tumors became palpable. Treatment of athymic nude mice bearing A3.01 (T-lymphoblast), Molt-4 (T-cell leukemia), CaPan-2 (pancreatic adenocarcinoma), CaLu-3 (non-small-cell lung adenocarcinoma), LS174T and T84 (colon adenocarcinoma), and Daudi (B-cell lymphoma) human tumor xenografts with MM significantly inhibited s.c. tumor growth. Treatment of BALB/c mice with MM after i.v. injection of murine RAW117-H10 lymphoma cells in an experimental metastasis assay resulted in increased survival time for treated animals. No significant inhibitory effect on s.c. tumor outgrowth was seen with MM treatment of SK-Hep-1, a human hepatic endothelioma, or Hep-3B, a liver adenocarcinoma, at any of the doses tested.
 ...
PMID:Anti-tumor activity of mycophenolate mofetil against human and mouse tumors in vivo. 818 60

A chimeric toxin has been constructed by fusion of a gene encoding human interleukin 4 (hIL4) to a gene encoding a mutant form of Pseudomonas exotoxin A (PE) which cannot bind to its receptors (PE4E). The chimeric gene was expressed in Escherichia coli where large amounts of the chimeric toxin, hIL4-PE4E, was produced. Purified hIL4-PE4E was very cytotoxic to cancer cell lines of both hematopoietic and solid tumor origin. In the HUT 102 T cell leukemia and Daudi B cell lymphoma cell lines, protein synthesis was inhibited by 50% (ID50) at a hIL4-PE4E concentration of 2 and 7 ng/ml (25 and 86 pM, respectively). hIL4-PE4E was also very cytotoxic to cell lines derived from carcinomas of the colon, breast, stomach, liver, adrenals, and prostate, as well as melanoma and epidermoid carcinoma, indicating that hIL4 receptors are widely expressed on human malignancies. We also found that human phytohemagglutinin-activated peripheral blood lymphocytes were extremely sensitive to hIL4-PE4E with an ID50 of 0.2 ng/ml (2.5 pM). The cytotoxic action of hIL4-PE4E was specific because it was blocked by an excess of hIL4 and not of human interleukin 2. In addition, hIL4-PE4ED553, an enzymatically inactive form of the chimeric toxin, was not cytotoxic. These results suggest that the hIL4 receptor may be a target for therapy in malignant and immunologic disorders using hIL4 chimeric toxin.
 ...
PMID:A wide range of human cancers express interleukin 4 (IL4) receptors that can be targeted with chimeric toxin composed of IL4 and Pseudomonas exotoxin. 831 73

To develop new purging regimens for ABMT the ability to predict potential for purging of tumor cells from BM is important. Since the sensitivity of human B cell lymphoma to hyperthermia is not known, we examined its effect on the growth of B cell lymphoma cell lines (Raji and Daudi) in vitro to evaluate potential for purging clonogenic tumor cells from normal marrow by heat, using a limiting dilution assay to measure log depletion of tumor cells in a 20-fold excess of normal BM. When exposed to heat (42-43 degrees C) for 120 min, both clonogenic Raji and Daudi cells were dramatically reduced (a 4-to-6 log reduction) with time, whereas at 42 degrees C over half and at 43 degrees C 10% of normal granulocyte-macrophage progenitor cells survived for the same time period. This high level of lymphoma cell depletion by heat correlated with that of immunologic and pharmacologic studies. In addition, these survival curves during heating were found to correlate with the Gompertz-Makeham formula--a law of human mortality. This formula may be useful in predicting the purging effect of heat. These results suggest that in vitro hyperthermia could be applied effectively for the elimination of residual, clonogenic lymphoma cells in autologous marrow grafts before ABMT.
 ...
PMID:Prediction of the ability to purge clonogenic B cell lymphoma from normal BM in vitro by heat: their survival curves correspond to a curve reflecting mortality in humans. 833 23

A procedure for amplifying and detecting nucleic acid sequences in situ using cells in suspension and flow cytometry has been developed. The process involves the use of the polymerase chain reaction (PCR) and a fluorescent in situ hybridization (FISH) protocol developed in our laboratory to detect the amplified PCR product. For these studies, a Y-chromosome specific repeat DNA sequence was amplified. Daudi cells, a B-cell lymphoma culture line established from a male, was used as a positive control and HL-60, a promyelocytic leukemia culture line established from a female, was used as a negative control. During the in situ PCR process cellular autofluorescence (noise) increases causing markedly reduced detection sensitivity of the probe (signal) bound to the amplified product within the positive cells. An autofluorescence reduction circuit was applied which was integrated into as standard bench top flow cytometer to reduce this noise, thereby producing a 10-fold increase in detection sensitivity of the signal. Without the application of the autofluorescence reduction circuit, the positive control histogram distribution was virtually indistinguishable from the negative control sample distributions. After autofluorescence reduction, the data showed that the Y-chromosome DNA was only amplified in the Daudi cells subjected to the complete in situ PCR protocol. This increased sensitivity also provided direct detection of the Y-chromosome repeat sequence, albeit exhibiting less signal compared to the amplified target after the in situ PCR.
 ...
PMID:Amplification and detection of a Y-chromosome DNA sequence by fluorescence in situ polymerase chain reaction and flow cytometry using cells in suspension. 855 57

Cells undergoing apoptosis (programmed cell death) display profound morphologic and biochemical changes in the nucleus, cytoplasm, and plasma membrane. We have shown a direct temporal relationship between the onset of apoptosis in Jurkat T-cell lymphoblast cultures and a greater than two-fold increase in the signal intensity of the methylene resonance (at 1.3 ppm) as observed by proton nuclear magnetic resonance spectroscopy (1H NMR). The increase in the methylene resonance intensity was seen when apoptosis was induced by serum deprivation, glucocorticoid, and doxorubicin treatment but not in necrotic (nonapoptotic) cell death. We have found similar changes in a variety of other cell lines undergoing apoptosis including the Hut 78 T-cell leukemia, JY natural killer T-cell leukemia, Daudi B-cell lymphoma, HeLa, and 3T3 fibroblast cell lines. Furthermore, this spectral change was diminished in Bcl-2 overexpressing HL-60 cell cultures treated with doxorubicin, which were relatively resistant to apoptosis, as compared to apoptotic HL-60 cultures. 1H NMR spectroscopy therefore may be useful in detecting apoptotic cell death in vivo.
 ...
PMID:Detection of apoptotic cell death by proton nuclear magnetic resonance spectroscopy. 863 43

We have cloned the cDNA encoding the human ornithine decarboxylase antizyme from a 5'-stretch cDNA library of human B-cell lymphoma Daudi. The cloned human antizyme cDNA fragment consists of 1063 bp, has 80% homology to the rat antizyme cDNA, but shows almost no homology to the E. coli antizyme gene. Northern hybridization analysis shows that this gene is expressed in a number of human cell lines with an estimated mRNA transcript size of about 1.1 kb. The size of the mRNA suggests that the cloned cDNA fragment probably represents the full length of human antizyme mRNA transcript. Comparison of the human and rat antizymes demonstrates that they are highly conserved at both nucleotide and peptide levels.
 ...
PMID:Molcecular cloning of human antizyme cDNA. 913 64

The CD20 antigen is an attractive target for specific treatment of B-cell lymphoma. Antibody-directed enzyme prodrug therapy (ADEPT) aims at the specific activation of a nontoxic prodrug at the tumor site by an enzyme targeted by a tumor-specific antibody such as anti-CD20. We constructed a fusion protein of the single-chain Fv anti-CD20 mouse monoclonal antibody (MoAb) 1H4 and human beta-glucuronidase for the activation of the nontoxic prodrug N-[4-doxorubicin-N-carbonyl(-oxymethyl) phenyl] O-beta-glucuronyl carbamate to doxorubicin at the tumor site. The cDNAs encoding the light- and heavy-chain variable regions of 1H4 were cloned, joined by a synthetic sequence encoding a 15-amino acid linker and fused to human beta-glucuronidase by a synthetic sequence encoding a 6-amino acid linker. An antibody-enzyme fusion protein-producing cell line was established by transfection of the construct into human embryonic kidney 293/EBNA cells. The yield of active fusion protein was 100 ng/mL transfectoma supernatant. Antibody affinity, antibody specificity, and enzyme activity were fully retained by the fusion protein. Immunoprecipitation and analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) showed that the fusion protein has a relative molecular weight (Mw) of 100 kD under denaturing conditions. Gel filtration analysis indicated that the enzymatically active form of the fusion protein is a tetramer with an Mw of approximately 400 kD. The nontoxic prodrug N-[4-doxorubicin-N-carbonyl(-oxymethyl) phenyl] O-beta-glucuronyl carbamate was hydrolyzed by the fusion protein at a hydrolysis rate similar to that of human beta-glucuronidase. When the fusion protein was specifically bound to Daudi lymphoma cells, the prodrug induced similar antiproliferative effects as doxorubicin. Thus, it is feasible to construct a eukaryotic fusion protein consisting of a single-chain anti-CD20 antibody and human beta-glucuronidase for future use in the activation of anticancer prodrugs in B-cell lymphoma.
 ...
PMID:Construction and characterization of a fusion protein of single-chain anti-CD20 antibody and human beta-glucuronidase for antibody-directed enzyme prodrug therapy. 963 15

Long-circulating submicron lipid emulsions, stabilized with poly(ethylene glycol)-modified phosphatidylethanolamine (PEG-PE), are promising drug carriers with substantial capacity for solubilization of lipophilic anticancer agents. This study describes the conjugation of the anti-B-cell lymphoma monoclonal antibody LL2 to the surface of lipid-emulsion globules by use of a novel poly(ethylene glycol)-based heterobifunctional coupling agent. The efficiency of coupling of LL2 to the lipid emulsion was 85% (approx.) and essentially independent of the LL2/emulsion particle ratio and amount of surface-bound PEG-PE. Results from sucrose-gradient centrifugation and Sepharose CL-4B gel filtration indicated stable binding of the antibody to the emulsion. The immunoreactivity of the emulsion-LL2 conjugates was tested with alkaline phosphatase-conjugated LL2 against a monoclonal anti-idiotype antibody, WN. The binding of the conjugates to WN increased with increasing surface density of LL2 up to 40 monoclonal antibodies/emulsion particle, and exceeded that for the free monoclonal antibody (approx. 20 molecules/particle). Results from competitive-binding ELISA were indicative of similar displacement curves for free LL2 and emulsion-LL2 conjugates. Direct cellular ELISA revealed similar binding of emulsion-LL2 complexes to three types of Burkitt's lymphoma cell lines, Raji, Ramos and Daudi. The results from this study indicate that emulsion-LL2 complexes might be a useful drug-carrier system for more specific delivery of anticancer drugs to B-cell malignancy.
 ...
PMID:Conjugation of an anti-B-cell lymphoma monoclonal antibody, LL2, to long-circulating drug-carrier lipid emulsions. 1057 80

In the present study the cell surface expression of CD45 isoforms on normal and neoplastic human B cells was correlated with splice products of the CD45 mRNA, using RT-PCR technology. In non-Hodgkin's lymphoma cells in the leukemic phase (NHL) the majority of the cells expressed a high level of CD45RA, while in CLL most of the cells expressed a low level. In the Raji and Daudi Burkitt B-cell lymphoma lines the main CD45 mRNA product was the largest, unspliced, full-length isoform (456) and the 56 splice product. Similar results were obtained with B-cell lymphoma cells isolated from the peripheral blood of patients with NHL in the leukemic phase. In EBV-transformed B-cell lines, the 456 and the 56 isoform of CD45 mRNA were predominant, but in addition a low level of the 5- and 0-exon splice products was detected. A strikingly different pattern was obtained with B-CLL cells. In CLL the level of the 456 and the 56 isoforms was low, while that of the 5- and 0-exon splice products was increased. Thus, in contrast to the heterogeneity in the expression of CD45RO in B-CLL, the majority of the cells contained the CD45 mRNA splice product coding for CD45RO. Analysis of splice products of the CD45 mRNA may serve as an additional tool to differentiate CLL from the leukemic phase of NHL.
 ...
PMID:B-lymphocytes in CLL and NHL differ in the mRNA splicing pattern of the CD45 molecule. 1090 91

LL2, an anti-CD22 monoclonal antibody against B-cell lymphoma, was covalently linked to the amphibian ribonuclease, onconase, a member of the pancreatic RNase A superfamily. LL2 increased in vitro potency (10 000-fold) and specificity against human Daudi Burkitt lymphoma cells while decreasing systemic toxicity of onconase. Monensin further increased potency of LL2-onconase on Daudi cells (IC(50), 20 and 1.5 pM, absence and presence of monensin, respectively). A 1-hour exposure to LL2-onconase was sufficient to kill Daudi cells in culture. These favorable in vitro properties translated to significant antitumor activity against disseminated Daudi lymphoma in mice with severe combined immunodeficiency disease. In mice inoculated with tumor cells intraperitoneally (ip), LL2-onconase (100 microg 5 times ip every day) increased the life span of animals with minimal disease 200%. The life span of mice with advanced disseminated Daudi lymphoma (tumor cells inoculated intravenously) was increased 135%. Mice injected with LL2-onconase tolerated a dose as high as 300 mg/kg. Because both onconase and LL2 are in clinical trials as cancer therapeutics, the covalently linked agents should be considered for treatment of non-Hodgkin lymphoma.
 ...
PMID:Potent and specific antitumor effects of an anti-CD22-targeted cytotoxic ribonuclease: potential for the treatment of non-Hodgkin lymphoma. 1115 33


<< Previous 1 2 3 4 5 6 Next >>