nbk

BACKGROUND: Periodontitis and immune dysfunction are often reported in alcohol-dependent patients. Our objectives were to investigate the effects of alcohol exposure on neutrophil function and the associated consequential effects on the periodontium in a group of African American (AA) males with documented history of alcohol use without medical complications. METHODS: Thirty-three AA males with documented history of alcohol use were included in this analysis. All subjects were free from systemic illness...

PURPOSE: Ovarian cancer has the highest mortality rate of all female reproductive malignancies. Drug resistance is a major cause of treatment failure and novel therapeutic strategies are urgently needed. MLN4924 is a NEDDylation inhibitor currently under investigation in multiple phase I studies. We investigated its anticancer activity in cisplatin-sensitive and -resistant ovarian cancer models. EXPERIMENTAL DESIGN: Cellular sensitivity to MLN4924/cisplatin was determined by measuring viability, clonogenic survival, and apoptosis...

FA (Fanconi anaemia) is a rare hereditary disorder characterized by congenital malformations, progressive bone marrow failure and an extraordinary predisposition to develop cancer. At present, 15 genes have been related to this condition and mutations of them have also been found in different types of cancer. Bone marrow failure threatens the life of FA patients during the first decade of their life, but the mechanisms underlying this process are not completely understood. In the present study we investigate a possible imbalance between the expression of pro- and anti-apoptotic proteins as a cause for the hypersensitivity of FANCC (FA, complementation group C)-deficient cells to genotoxic stress...

PURPOSE: The purpose of this study is to determine the association between the BIK/NBK gene expression and estrogen receptor alpha expression. MATERIALS AND METHODS: We determined the association of BIK/NBK gene expression by real time quantitative reverse transcription polymerase chain reaction and estrogen receptor alpha expression by immunohistochemistry in samples of breast cancer tissue. RESULTS: We found a statistically significant correlation of BIK/NBK gene expression with the estrogen receptor alpha expression (ρ = 0...

BH3 mimetic drugs induce cell death by antagonizing the activity of antiapoptotic Bcl-2 family proteins. Cyclin-dependent kinase (CDK) inhibitors that function as transcriptional repressors downregulate the Bcl-2 family member Mcl-1 and increase the activity of selective BH3 mimetics that fail to target this protein. In this study, we determined whether CDK inhibitors potentiate the activity of pan-BH3 mimetics directly neutralizing Mcl-1. Specifically, we evaluated interactions between the prototypical pan-CDK inhibitor flavopiridol and the pan-BH3 mimetic obatoclax in multiple myeloma (MM) cells in which Mcl-1 is critical for survival...

Biobanking became a necessity for translating genetic discoveries into clinical practice. Approaches to personalized medicine require a new model system for functional and pharmacogenomic studies of a variety of accumulating genetic variations, as well as new research environments such as biobankomics. Human lymphoblastoid cell lines (LCLs) will provide a valuable tool to meet such new demands in the biobankomics era. The National Biobank of Korea (NBK), which is leading the Korea Biobank Project, has a large collection of LCLs derived mostly from population-based cohort samples...

BACKGROUND: although gene expression profile of multiple myeloma (MM) patients shows a wide range of Bik/Nbk expression, varying from absent to high, its regulation and function in myeloma cells is poorly understood. Thus, we addressed these questions in MM. METHODS: human myeloma cell lines (HMCLs) and primary purified myeloma cells were studied for Bcl-2 family protein expression by western blot and further correlation analysis was performed. Correlative study between Bik and thyrotroph embryonic factor (TEF) transcription factor expression was analysed by PCR...

The National Biobank of Korea (NBK) is a government supported project that aims at consolidating various human-originated biomedical resources collected by individual hospitals nation-wide and integrating them with their donors' clinical information which researchers can take advantage of. In this paper, we present our experiences in developing the Clinical Information Integration System (CIIS) for NBK. The system automatically extracts clinical data from hospital information systems as much as possible to avoid errors from manual entry by human errors...

Transcriptional activation of gene expression directed by the long terminal repeat (LTR) of HIV-1 requires both the transactivation response element (TAR) and Tat protein. HIV-1 mutants lacking a functional tat gene are not able to proliferate. Here we take a genetic approach to suppress HIV-1 replication based on Tat-dependent production of MazF, an ACA-specific endoribonuclease (mRNA interferase) from Escherichia coli. When induced, MazF is known to cause Bak- and NBK-dependent apoptotic cell death in mammalian cells...

INTRODUCTION: Ataxia telangiectasia (AT) is an autosomal recessive multisystem disorder characterized by variable immunodeficiency, progressive neurodegeneration, occulocutaneous telangiectasia, and an increased susceptibility to malignancies. This study was designed to study the role of proapoptotic BAK, BAX, and NBK/BIK genes in a group of patients with AT to elucidate the possible role of these genes in progression of malignancies in this disease. MATERIALS AND METHODS: Fifty Iranian patients with AT were investigated in this study...

Karenia brevis, the major harmful algal (HA) species in the Gulf of Mexico, produces a suite of brevetoxins and brevenal, a nontoxic brevetoxin antagonist. K. brevis growth is reported to be optimum at oceanic conditions, yet blooms are most problematic in coastal waters. Differences in growth rate, total brevetoxin production, brevetoxin profiles and brevenal production were evaluated among eight K. brevis clones grown at salinities of 35 and 27, but otherwise identical conditions. All measured parameters varied significantly among clones and the individual responses to decreased salinity varied as well...

IFNgamma induces cell death in epithelial cells, but the mediator for this death pathway has not been identified. In this study, we find that expression of Bik/Blk/Nbk is increased in human airway epithelial cells (AECs [HAECs]) in response to IFNgamma. Expression of Bik but not mutant BikL61G induces and loss of Bik suppresses IFNgamma-induced cell death in HAECs. IFNgamma treatment and Bik expression increase cathepsin B and D messenger RNA levels and reduce levels of phospho-extracellular regulated kinase 1/2 (ERK1/2) in the nuclei of bik(+/+) compared with bik(-/-) murine AECs...

Effective treatments for androgen-independent prostate cancer (AIPCa) are lacking. To address this, emerging therapeutics such as proteasome inhibitors are currently undergoing clinical trials. Inositol hexakisphosphate (IP6) is an orally non-toxic phytochemical that exhibits antitumour activity against several types of cancer including PCa. We have previously shown that treatment of PC3 cells with IP6 induces the transcription of a subset of nuclear factor-kappaB (NF-kappaB)-responsive and pro-apoptotic BCL-2 family genes...

Gene expression of carbonyl-metabolizing enzymes (CMEs) was investigated in normal buccal keratinocytes (NBK) and the transformed buccal keratinocyte lines SVpgC2a and SqCC/Y1. Studies were performed at a serum concentration known to induce terminal squamous differentiation (TSD) in normal cells. Overall, 39 of 58 evaluated CMEs were found to be expressed at the transcript level. Together the transformed cell lines showed altered transcription of eight CME genes compared to NBK, substantiating earlier results...

3-[(2,2,6,6-Tetramethylpiperidine-4-ylimino)methyl]rifamycin (4) and spin-labeled rifamycin-3-[(2,2,6,6- tetramethyl-1-oxyl-piperidine-4-ylimino)methyl]rifamycin (1) were prepared. The structures of these compounds were determined by IR, UV, MS and 1H NMR of 4. The ESR-spectrum of 1 is a symmetric triplet signal, characteristic of nitroxyl radicals, g = 2.0025. An in vitro comparative study of the cytotoxicity and antitumor activity of 1, 4 and the initial 3-formyl-rifamycin was carried out in concentrations from 0...

In the last decades melanoma incidence has been increasing worldwide, while mortality remained on a high level. Until now, there is no suitable therapy for metastasized melanoma, which could lead to a significant increase in overall survival. Apoptosis deficiency is supposed to be a critical factor for therapy resistance, and previous work has characterized the basic mechanisms of apoptosis regulation in melanoma. Genes and strategies suitable for efficient induction of apoptosis in melanoma cells were identified, which are based on proapoptotic Bcl-2 proteins (Bcl-x(S), Bcl-x(AK), Bik/Nbk and Bax) as well as on tumor necrosis factor (TNF)-related death ligands (CD95L/Fas ligand and TNF-related apoptosis-inducing ligand, TRAIL)...

B cell lymphoma 2 (Bcl-2) homology domain 3 (BH3)-only proteins of the Bcl-2 family are important functional adaptors that link cell death signals to the activation of Bax and/or Bak. The BH3-only protein Nbk/Bik induces cell death via an entirely Bax-dependent/Bak-independent mechanism. In contrast, cell death induced by the short splice variant of Bcl-x depends on Bak but not Bax. This indicates that Bak is functional but fails to become activated by Nbk. Here, we show that binding of myeloid cell leukemia 1 (Mcl-1) to Bak persists after Nbk expression and inhibits Nbk-induced apoptosis in Bax-deficient cells...

Ribonucleases, antibiotics, bacterial toxins, and viruses inhibit protein synthesis, which results in apoptosis in mammalian cells. How the BCL-2 family of proteins regulates apoptosis in response to the shutoff of protein synthesis is not known. Here we demonstrate that an Escherichia coli toxin, MazF, inhibited protein synthesis by cleavage of cellular mRNA and induced apoptosis in mammalian cells. MazF-induced apoptosis required proapoptotic BAK and its upstream regulator, the proapoptotic BH3-only protein NBK/BIK, but not BIM, PUMA, or NOXA...

We report for the first time inactivation of a tissue-specific Bcl-2 homology domain 3 (BH3)-only protein as a common aspect in human cancer. In detail, we show that loss of the BH3-only protein natural born killer (Nbk)/Bcl-2-interacting killer (Bik) is a common feature of clear-cell renal cell carcinoma (RCC). While strong Nbk expression is found in the renal tubuli and the epithelial lining of the glomerula, a consistent loss of Nbk expression was observed in primary RCC tissue and RCC cell lines. Mutation of Nbk is, however, rare, whereas deletion of the Nbk gene at 22q13...

BACKGROUND: Breast cancer is one of the most frequent causes of death in Mexican women over 35 years of age. At molecular level, changes in many genetic networks have been reported as associated with this neoplasia. To analyze these changes, we determined gene expression profiles of tumors from Mexican women with breast cancer at different stages and compared these with those of normal breast tissue samples. METHODS: 32P-radiolabeled cDNA was synthesized by reverse transcription of mRNA from fresh sporadic breast tumor biopsies, as well as normal breast tissue...