Abstract:
:The overexpression of prosurvival members of the Bcl-2 family is commonly associated with the enhanced malignancy of hematological tumors. There has been great interest in a novel set of agents that are able to mimic the function of the BH3 domain by binding to the groove of Bcl-2-like proteins and initiating the cell death sequence. We sought to examine the efficacy of BH3 mimetics in a spontaneous mouse model of B-cell neoplasia. We evaluated the ability of the BH3 mimetics to preferentially target tumor cells while sparing normal cells. In addition, we examined the contributions of Bim and Puma to the sensitivity of tumor cells to the BH3 mimetics. We report here that two BH3 mimetics (HA-14-1 and BH3-I-2') were able to induce apoptosis of murine B-cell lymphoma cells in vitro and in vivo. Tumors that arose from transplantation of primary lymphoma cells regressed following 7 days of treatment with BH3-mimetic drugs. The long-term benefits of the transient treatment of tumor-bearing mice with the BH3 mimetics, however, could not be properly evaluated, due to the high levels of toxicity we observed in vivo with these drugs. Decreased expression of either Bim or Puma from B-cell tumor cells was able to protect these cells from the apoptosis induced by these BH3 mimetics, suggesting that they function through other means. We conclude that while the BH3-mimetic drugs are effective at inducing cell death of lymphoma cells in vitro and in vivo, their unclear molecular specificity and their ability to kill normal cells may limit their therapeutic uses in humans.
journal_name
DNA Cell Bioljournal_title
DNA and cell biologyauthors
Turner BC,Eves T,Refaeli Ydoi
10.1089/dna.2007.0675subject
Has Abstractpub_date
2008-03-01 00:00:00pages
133-42issue
3eissn
1044-5498issn
1557-7430journal_volume
27pub_type
杂志文章abstract::Endogenous phytohormones auxin (indole-3-acetic acid [IAA]), abscisic acid (ABA), gibberellin (GA3), and brassinosteroid (BR) play a role in responses to drought stress in higher plants. Tea plant is one of the major economic corps worldwide. The tender shoots of tea plants are the main source for tea production. The ...
journal_title:DNA and cell biology
pub_type: 杂志文章
doi:10.1089/dna.2019.4896
更新日期:2019-11-01 00:00:00
abstract::Most studies on the tissue distribution of actin isoform transcripts have been done in small mammals such as rat and mouse. We have begun a characterization of the actin gene family in a large mammal, the bovine. The alpha skeletal gene was isolated, and an isoform-specific probe to the 3' untranslated region of the t...
journal_title:DNA and cell biology
pub_type: 杂志文章
doi:10.1089/dna.1995.14.555
更新日期:1995-06-01 00:00:00
abstract::Hepatocellular carcinoma (HCC) is a life-threatening disease that is often associated with chronic infection by hepatitis B and C viruses. Genetic polymorphisms have been reported to alter the risk for HCC development. Genetic studies based on the haplotype have an increased power for detecting disease associations co...
journal_title:DNA and cell biology
pub_type: 杂志文章
doi:10.1089/dna.2009.0921
更新日期:2009-11-01 00:00:00
abstract::The development of the pancreas is a complicated process that is regulated on several levels. Pancreas transcription factor 1, alpha subunit (Ptf1a), also known as p48, is a pancreas-specific basic helix-loop-helix transcription factor that is critical for both exocrine pancreas development and maintenance of acinar c...
journal_title:DNA and cell biology
pub_type: 杂志文章
doi:10.1089/dna.2012.1619
更新日期:2012-07-01 00:00:00
abstract::Global antibiotic resistance, driven by intensive antibiotic exposure/abuse, constitutes a serious challenge to all health care, particularly in an era when new antimicrobial development has slowed to a trickle. Recently, we published work demonstrating the discovery and partial mechanism of action of a novel bacteric...
journal_title:DNA and cell biology
pub_type: 杂志文章,评审
doi:10.1089/dna.2020.5824
更新日期:2020-09-01 00:00:00
abstract::dTMP kinase (E.C.2.7.4.9.) catalyzes the phosphorylation of dTMP to the corresponding diphosphate. This enzyme is essential for DNA synthesis in vivo and is an important intermediate enzyme in the pathway of many pyrimidine analog drugs. In this report, we describe the isolation of the human dTMP kinase gene by functi...
journal_title:DNA and cell biology
pub_type: 杂志文章
doi:10.1089/dna.1994.13.461
更新日期:1994-05-01 00:00:00
abstract::Sterol carrier protein2 (SCP2) is a 13.2-kD protein that is thought to be involved in the intracellular transport of cholesterol. Using synthetic oligonucleotides based on the protein sequence of SCP2, a clone (SP43) was isolated from a rat liver cDNA library. The DNA sequence revealed that the cDNA could encode a pol...
journal_title:DNA and cell biology
pub_type: 杂志文章
doi:10.1089/dna.1990.9.159
更新日期:1990-04-01 00:00:00
abstract::Polyhomeotic is a member of the Polycomb group of genes. The products of this group are chromatin-associated proteins that act together as multimeric complexes. These proteins are required for the maintenance of target gene repression in a permanent and heritable manner during development. In order to better understan...
journal_title:DNA and cell biology
pub_type: 杂志文章
doi:10.1089/104454901316976118
更新日期:2001-08-01 00:00:00
abstract::The aim of this work was to express a eukaryotic pre-protein in Escherichia coli so that it could be obtained intact, without cleavage, by bacterial leader peptidase. To this end, cDNA coding for honeybee prepromelittin was ligated to the 3' end of genes coding for truncated forms of either Protein A or beta-galactosi...
journal_title:DNA and cell biology
pub_type: 杂志文章
doi:10.1089/dna.1994.13.875
更新日期:1994-08-01 00:00:00
abstract::The major surface glycoprotein (MSG) of Pneumocystis carinii is encoded by a family of related but distinct genes distributed throughout the P. carinii genome. Previous reports of the genomic and mRNA MSG structure suggested that there was a highly conserved 5'-untranslated region and a highly variable translated regi...
journal_title:DNA and cell biology
pub_type: 杂志文章
doi:10.1089/dna.1996.15.989
更新日期:1996-11-01 00:00:00
abstract::The search for new chemotherapeutics unaffected by efflux pumps would significantly increase life expectancy in patients with malignant cancers. In this study, butylcycloheptylprodigiosin and undecylprodigiosin were HPLC-purified and verified, using nuclear magnetic resonance spectroscopy. Cell cytotoxicity and transp...
journal_title:DNA and cell biology
pub_type: 杂志文章
doi:10.1089/dna.2018.4161
更新日期:2018-06-01 00:00:00
abstract::Haplotypes formed by polymorphisms (T-786C, rs2070744; a variable number of tandem repeats in intron 4, and Glu298Asp, rs1799983) of the eNOS gene were associated previously with gestational hypertension (GH) and preeclampsia (PE). However, no study has explored the Tag SNPs rs743506 and rs7830 in these disorders. The...
journal_title:DNA and cell biology
pub_type: 杂志文章
doi:10.1089/dna.2012.1768
更新日期:2012-12-01 00:00:00
abstract::Cardiomyocytes are notoriously difficult to transfect using standard techniques unless viral vectors such as recombinant adenoviruses are used. Generation of recombinant adenoviruses is, however, a complex and time-consuming procedure and not possible for every DNA construct. We therefore optimized DNA/polylysine/aden...
journal_title:DNA and cell biology
pub_type: 杂志文章
doi:10.1089/dna.2005.24.381
更新日期:2005-06-01 00:00:00
abstract::In our previous study, a kind of novel hybrid immunoglobulin (Ig)-binding proteins (IBPs) was obtained with the characteristic structure of alternately arranged Finegoldia magna (formerly Peptostreptococcus magnus) protein L (P. magnus protein L, PpL) B3 domain (B3) and Staphylococcal protein A (SpA) D domain (D). In ...
journal_title:DNA and cell biology
pub_type: 杂志文章
doi:10.1089/dna.2007.0708
更新日期:2008-08-01 00:00:00
abstract::Non-Hodgkin lymphoma (NHL) is the most common hematologic malignancy worldwide. Interleukin-2 (IL-2) plays a key role in the proliferation of T cells and natural killer cells. It has been reported that polymorphisms in the IL-2 gene are associated with various cancers. The aim of this study was to examine the effect o...
journal_title:DNA and cell biology
pub_type: 杂志文章
doi:10.1089/dna.2011.1603
更新日期:2012-07-01 00:00:00
abstract::Endocytosis of the five rat somatostatin receptor subtypes (SSTR1-5) was investigated in transfected HEK cells by biochemical ligand binding assays and confocal microscopic analysis. Phenylarsine oxide-sensitive internalization of SSTR1-3 is dependent on SST-14 or SST-28, whereas only the octacosapeptide triggers this...
journal_title:DNA and cell biology
pub_type: 杂志文章
doi:10.1089/dna.1997.16.111
更新日期:1997-01-01 00:00:00
abstract::Immune dysregulation has been implicated in myelodysplastic syndrome (MDS) pathogenesis. Refractory anemia with ringed sideroblasts (RARS) is a low-risk subtype of MDS. Our previous study has reported an abnormal γδ T cell receptor (TCR) repertoire in patients with intermediate or high-risk MDS. To characterize the st...
journal_title:DNA and cell biology
pub_type: 杂志文章
doi:10.1089/dna.2015.2925
更新日期:2015-09-01 00:00:00
abstract::Long noncoding RNAs (lncRNAs) may serve as potential molecular diagnostic markers to improve the capacity of earlier and more accurate diagnosis of dilated cardiomyopathy (DCM). We integrated five independent transcriptomic datasets (n = 504) from Gene Expression Omnibus for systematic identification of lncRNA-based d...
journal_title:DNA and cell biology
pub_type: 杂志文章
doi:10.1089/dna.2020.5670
更新日期:2020-11-03 00:00:00
abstract::The gene for the bovine oxytocin receptor has been sequenced using a combination of clones derived from a bovine endometrial cDNA library from estrus and a bovine genomic DNA library, with confirmation of structure using reverse transcription PCR programmed by term myometrial RNA. The receptor belongs to the seven tra...
journal_title:DNA and cell biology
pub_type: 杂志文章
doi:10.1089/dna.1995.14.1037
更新日期:1995-12-01 00:00:00
abstract::Regenerative medicine is a new interdisciplinary field in biomedical science, which aims at the repair or replacement of the defective tissue or organ by congenital defects, age, injury, or disease. Various cell-related techniques such as stem cell-based biotherapy are a hot topic in the current press, and stem cell r...
journal_title:DNA and cell biology
pub_type: 杂志文章,评审
doi:10.1089/dna.2013.2104
更新日期:2013-10-01 00:00:00
abstract::Sterol regulatory element-binding proteins (SREBPs) are transcription factors governing transcription of genes related to cholesterol and fatty acid metabolism. To become active, SREBPs must undergo a proteolytic cleavage to allow an active NH(2)-terminal segment to translocate into the nucleus. SKI-1/S1P is the first...
journal_title:DNA and cell biology
pub_type: 杂志文章
doi:10.1089/dna.2007.0624
更新日期:2007-11-01 00:00:00
abstract::Administration of endotoxin (LPS) in humans results in profound physiological responses, including activation of peripheral blood mononuclear cells and the release of inflammatory factors. The time course of the response of selected inflammatory proteins was examined in healthy subjects (n = 6) administered a single i...
journal_title:DNA and cell biology
pub_type: 临床试验,杂志文章
doi:10.1089/dna.2005.24.410
更新日期:2005-07-01 00:00:00
abstract::Deer antlers are amazing natural appendages that grow faster than any other known mammalian bone. Antler growth occurs at the tip and is initially cartilage, which is later replaced by bone tissue. However, little is known regarding the precise role of cooperation between cell lineages and functional genes in regulati...
journal_title:DNA and cell biology
pub_type: 杂志文章
doi:10.1089/dna.2017.3885
更新日期:2018-01-01 00:00:00
abstract::KCNQ1 overlapping transcript 1 (KCNQ1OT1), a long noncoding RNA responsible for silencing a cluster of genes in cis, has been shown to be involved in multiple cancers. However, much remains unclear of how KCNQ1OT1 contributes to carcinogenesis. By thoroughly analyzing 510 hepatocellular carcinoma (HCC) cases and 1014 ...
journal_title:DNA and cell biology
pub_type: 杂志文章
doi:10.1089/dna.2013.2118
更新日期:2013-11-01 00:00:00
abstract::Hearing loss in Ménière's disease (MD) is associated with loss of spiral ganglion neurons and hair cells. In a guinea pig model of endolymphatic hydrops, nitric oxide synthases (NOS) and oxidative stress mediate loss of spiral ganglion neurons. To test the hypothesis that functional variants of NOS1 and NOS2A are asso...
journal_title:DNA and cell biology
pub_type: 杂志文章
doi:10.1089/dna.2011.1259
更新日期:2011-09-01 00:00:00
abstract::We have determined the expression pattern of all 11 human replication-dependent histone H3 genes in three fetal human tissues (bladder, liver, and lung) and in eight human cell lines by RNase protection assay. In the fetal human tissues, all 11 genes were expressed to a varied extent. However, the relative contributio...
journal_title:DNA and cell biology
pub_type: 杂志文章
doi:10.1089/104454903321908629
更新日期:2003-04-01 00:00:00
abstract::The pathogenic strains of Vibrio cholerae that cause acute enteric infections in humans are derived from environmental nonpathogenic strains. To track the evolution of pathogenic V. cholerae and identify potential precursors of new pathogenic strains, we analyzed 324 environmental or clinical V. cholerae isolates for ...
journal_title:DNA and cell biology
pub_type: 杂志文章
doi:10.1089/dna.2008.0737
更新日期:2008-07-01 00:00:00
abstract::Insulin-like growth factor I (IGF-I) plays a major role in development and metabolism. Currently, the cDNA-derived primary structure of IGF-I is known for some mammals and for chicken, frog, and salmon. Additionally, the organization of the human, rat, and chicken IGF-I genes has been established. The investigation of...
journal_title:DNA and cell biology
pub_type: 杂志文章
doi:10.1089/dna.1993.12.729
更新日期:1993-10-01 00:00:00
abstract::Eaf2 encodes a tumor suppressor that plays multiple functions in transcriptional activation, apoptosis, and embryonic development. In this study, we utilized GFP-EAF2 fusion protein to describe the dynamic subcellular movement of Eaf2. GFP-EAF2 is preferentially localized to the nucleus, and in the presence of ELL, it...
journal_title:DNA and cell biology
pub_type: 杂志文章
doi:10.1089/dna.2008.0733
更新日期:2008-12-01 00:00:00
abstract::Intracranial aneurysms (IAs) and potential IA rupture are one of the direct causes of permanent brain damage and mortality. Interestingly, the major risk factors of IA development, including hemodynamic stress, hypertension, smoking, and genetic predispositions, are closely associated with a proinflammatory immune sta...
journal_title:DNA and cell biology
pub_type: 杂志文章
doi:10.1089/dna.2015.3105
更新日期:2016-02-01 00:00:00