Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
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Target Concepts:
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Query: UMLS:C0079731 (
B-cell lymphoma
)
16,671
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
A murine homologue of the epithelial membrane protein 2 (EMP2) gene was identified in a search for genes associated with
B-cell lymphoma
tumorigenicity by using suppression subtractive hybridization. Expression of EMP2 messenger RNA in primary mouse tissues was limited to certain epithelial cell types and the peritoneal lymphoid compartment. EMP2 was expressed in the poorly tumorigenic
DAC
B-lymphoma cell line but was significantly down-regulated in a subline selected for in vivo tumor formation in Balb/c mice. Recombinant restoration of EMP2 expression in the subline suppressed its tumorigenicity, suggesting that loss of EMP2 was a causal factor in the malignant phenotype. Recombinant overexpression of EMP2 was studied in B lymphoma and NIH3T3 cells. EMP2 in both cell types induced cell death on serum deprivation. EMP2-induced cell death correlated with the expression level of EMP2 protein and was prevented by caspase inhibitors Z-VAD and Z-DEVD. These findings for the first time describe an apoptotic effect of a GAS3 family gene in lymphocytes. They also suggest that EMP2 may influence B-lymphoma tumorigenicity through a functional tumor suppressor phenotype. (Blood. 2001;97:3890-3895)
...
PMID:Epithelial membrane protein 2, a 4-transmembrane protein that suppresses B-cell lymphoma tumorigenicity. 1138 31
Aberrant promoter hypermethylation resulting in the epigenetic silencing of apoptosis-associated genes is a key process in the chemotherapeutic treatment of cancer. The nucleoside analog, 5-aza-2'deoxycytidine (
DAC
), inhibits the activity of DNA methyltransferase enzymes and is able to restore the expression levels of genes that have been silenced by aberrant DNA methylation. The aim of the present study was to investigate the effect of combined treatment with
DAC
and cisplatin (CDDP) on the lung adenocarcinoma cell line, P15. Growth inhibition was examined using a clone formation assay and growth inhibitory activities by cell counting during treatment with
DAC
alone, CDDP alone or
DAC
followed by CDDP. In addition, changes in the mRNA expression levels of various apoptosis-associated genes following treatment with increasing concentrations of
DAC
were determined using reverse transcription-polymerase chain reaction. Furthermore, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) analysis was used to detect the number of apoptotic P15 tumor cells following treatment with
DAC
and/or CDDP. The results indicated that
DAC
treatment alone restored the mRNA expression levels of
p73
,
p16
INK4a
,
B-cell lymphoma
(Bcl)-2-associated agonist of cell death and Bcl-2-associated X protein. In addition, combined therapy with
DAC
and CDDP was found to significantly suppress the growth of P15 tumor cells compared with
DAC
or CDDP treatment alone. In conclusion,
DAC
may enhance the chemosensitivity of the P15 cell line to treatment with CDDP.
...
PMID:Effect of combined 5-aza-2'deoxycytidine and cisplatin treatment on the P15 lung adenocarcinoma cell line. 2613 3
Background:
CD19-directed chimeric antigen receptor (CAR) T cells have substantial benefit in the treatment of patients with B-cell malignancies. However, despite encouraging therapeutic efficiency, there is limited overall response rate when anti-CD19 CAR-T cells are used to treat patients with relapsed and refractory (R/R) B cell lymphomas. Therefore, it further investigation is urgently needed to improve treatment efficacy.
Method:
A combined treatment protocol of CAR-T cell with decitabine (
DAC
) to treat
B cell lymphoma
was developed and tested on lymphoma cell lines first, and then efficacy and the underlying mechanism were investigated. After ethical approval was granted, the combined treatment protocol was applied to treat two patients with R/R B-cell lymphomas.
Results:
CAR-T cells were prepared successfully, and they recognized CD19 antigen expressed on lymphoma cell lines specifically. Cell-line studies also showed that CD19 antigen expression was increased by
DAC
pretreatment, and the function of CAR-T cells was not compromised. The cell-line study further demonstrated that lymphoma cells pretreated by
DAC
responded more to the treatment of CAR-T cells. Two patients with R/R
B cell lymphoma
were pretreated with
DAC
then treated with CAR-T, and both achieved complete remission (CR).
Conclusions:
The epigenetic modifying drug
DAC
increases expression of the surface antigen CD19 on lymphoma cells. The
DAC
pretreatment protocol may lead patients with
B cell lymphoma
to be more susceptible to adoptive transfer of anti-CD19 CAR-T cells treKeywordsatment.
...
PMID:Decitabine enhances cytotoxic effect of T cells with an anti-CD19 chimeric antigen receptor in treatment of lymphoma. 3137
Cell-of-origin subclassification of diffuse large
B cell lymphoma
(DLBCL) into activated B cell-like (ABC), germinal centre B cell-like (GCB) and unclassified (UNC) or type III by gene expression profiling is recommended in the latest update of the World Health Organization's classification of lymphoid neoplasms. There is, however, no accepted gold standard method or dataset for this classification. Here, we compare classification results using gene expression data for 68 formalin-fixed paraffin-embedded DLBCL samples measured on four different gene expression platforms (Illumina wG-DASL
TM
arrays, Affymetrix PrimeView arrays, Illumina TrueSeq RNA sequencing and the HTG EdgeSeq DLBCL Cell of Origin Assay EU using an established platform agnostic classification algorithm (
DAC
) and the classifier native to the HTG platform, which is CE marked for in vitro diagnostic use (CE-IVD). Classification methods and platforms show a high level of concordance, with agreement in at least 80% of cases and rising to much higher levels for classifications of high confidence. Our results demonstrate that cell-of-origin classification by gene expression profiling on different platforms is robust, and that the use of the confidence value alongside the classification result is important in clinical applications.
...
PMID:Comparative analysis of gene expression platforms for cell-of-origin classification of diffuse large B-cell lymphoma shows high concordance. 3324 57