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Andreas Borst, Sebastian Haferkamp, Johannes Grimm, Manuel Rösch, Guannan Zhu, Sen Guo, Chunying Li, Tianwen Gao, Svenja Meierjohann, David Schrama, Roland Houben
In patients with BRAF-mutated melanoma specific inhibitors of BRAF(V600E) and MEK1/2 frequently induce initial tumor reduction, frequently followed by relapse. As demonstrated previously, BRAF(V600E)-inhibition induces apoptosis only in a fraction of treated cells, while the remaining arrest and survive providing a source or a niche for relapse. To identify factors contributing to the differential initial response towards BRAF/MEK inhibition, we established M14 melanoma cell line-derived single cell clones responding to treatment with BRAF inhibitor vemurafenib and MEK inhibitor trametinib predominantly with either cell cycle arrest (CCA-cells) or apoptosis (A-cells)...
September 28, 2017: Cancer Letters
B Li, T-M Gao
BK channels are important for the regulation of many cell functions. The significance of plasma membrane BK channels in the control of action potentials, resting membrane potential, and neurotransmitter release is well established; however, the composition and functions of mitochondrial and nuclear BK (nBK) channels are largely unknown. In this chapter, we summarize the recent findings on the subcellular localization, biophysical, and pharmacological properties of mitochondrial and nBK channels and discuss their molecular identity and physiological functions...
2016: International Review of Neurobiology
Ryo Inoue, Kentarou Watanabe, Toyofusa Katou, Yasunori Ikezawa, Keita Hamasaki
Nucleobase modified neamines with a lysine as the linker (NbK-neamines) were synthesized and their binding toward hairpin RNAs derived from HIV-1 activator region were studied. NbK-neamines were bind those RNAs with micro molar level of binding affinities and compete with corresponding activator peptide for TAR RNA, but not for RRE RNA. GbK-neamine denotes the highest binding affinity with TAR RNA, three to five times higher than other three NbK-neamines. GbK-neamine could be a candidate of potential inhibitor for TAR-Tat...
May 1, 2015: Bioorganic & Medicinal Chemistry
Shuang Chen, Liang Zhou, Yu Zhang, Yun Leng, Xin-Yan Pei, Hui Lin, Richard Jones, Robert Z Orlowski, Yun Dai, Steven Grant
In selective autophagy, the adaptor protein SQSTM1/p62 plays a critical role in recognizing/loading cargo (e.g., malfolded proteins) into autophagosomes for lysosomal degradation. Here we report that whereas SQSTM1/p62 levels fluctuated in a time-dependent manner during autophagy, inhibition or knockdown of Cdk9/cyclin T1 transcriptionally downregulated SQSTM1/p62 but did not affect autophagic flux. These interventions, or short hairpin RNA (shRNA) directly targeting SQSTM1/p62, resulted in cargo loading failure and inefficient autophagy, phenomena recently described for Huntington's disease neurons...
September 15, 2014: Molecular and Cellular Biology
Boxing Li, Wei Jie, Lianyan Huang, Peng Wei, Shuji Li, Zhengyi Luo, Allyson K Friedman, Andrea L Meredith, Ming-Hu Han, Xin-Hong Zhu, Tian-Ming Gao
Ion channels are essential for the regulation of neuronal functions. The significance of plasma membrane, mitochondrial, endoplasmic reticulum and lysosomal ion channels in the regulation of Ca(2+) is well established. In contrast, surprisingly little is known about the function of ion channels on the nuclear envelope (NE). Here we demonstrate the presence of functional large-conductance, calcium-activated potassium channels (BK channels) on the NE of rodent hippocampal neurons. Functionally, blockade of nuclear BK channels (nBK channels) induces NE-derived Ca(2+) release, nucleoplasmic Ca(2+) elevation and cyclic AMP response element binding protein (CREB)-dependent transcription...
August 2014: Nature Neuroscience
Eva M Campion, Roya Hakimjavadi, Sinéad T Loughran, Susan Phelan, Sinéad M Smith, Brendan N D'Souza, Rosemary J Tierney, Andrew I Bell, Paul A Cahill, Dermot Walls
UNLABELLED: The Epstein-Barr virus (EBV) establishes a lifelong latent infection in humans. EBV infection of primary B cells causes cell activation and proliferation, a process driven by the viral latency III gene expression program, which includes EBV nuclear proteins (EBNAs), latent membrane proteins, and untranslated RNAs, including microRNAs. Some latently infected cells enter the long-lived memory B-cell compartment and express only EBNA1 transiently (Lat I) or no EBV protein at all (Lat 0)...
May 2014: Journal of Virology
Byunghak Kang, Jaesun Park, Sangyun Cho, Meehee Lee, Namhee Kim, Haesook Min, Sooyoun Lee, Ok Park, Bokghee Han
Many biobanks were established as biorepositories for biomedical research, and a number of biobanks were founded in the 1990s. The main aim of the biobank is to store and to maintain biomaterials for studying chronic disease, identifying risk factors of specific diseases, and applying personalized drug therapies. This report provides a review of biobanks, including Korean biobanks and an analysis of sample volumes, regulations, policies, and ethical issues of the biobank. Until now, the top 6 countries according to the number of large-scale biobanks are the United Kingdom, United States, Sweden, France, the Netherlands, and Italy, and there is one major National Biobank of Korea (NBK) and 17 regional biobanks in Korea...
December 2013: Genomics & Informatics
Jae-Eun Lee, Ji-Hyun Kim, Eun-Jung Hong, Hye Sook Yoo, Hye-Young Nam, Ok Park
Personalized medicine is emerging as a main paradigm for risk prediction, pre-diagnosis, and effective prevention and treatment of disease. A large number of human biospecimens and their clinical data are essential resources for the success of personalized medicine as well as other biomedical research. The National Biobank of Korea (NBK) has collected well-annotated and high quality human biospecimens, and distributes them to the Korean biomedical scientists, through the Korea Biobank Project (KBP). The ultimate goal of NBK activities is to promote biomedical research and public health...
September 2012: Osong Public Health and Research Perspectives
Sang Yun Cho, Eun Jung Hong, Jung Min Nam, Bogkee Han, Chaeshin Chu, Ok Park
On April 26, 2012, the Korea National Institute of Health officially held the opening ceremony of newly dedicated biobank building, 'NationalBiobank of Korea'. The stocked biospecimens and related information have been distributed for medical and public health researches. The Korea Biobank Project, which was initiated in 2008, constructed the Korea Biobank Network consisting of the National Biobank of Korea (NBK) with 17 regional biobanks in Korea. As of December 2011, a total of 525,416 biospecimens with related information have been secured: 325,952 biospecimens from the general population obtained through cohort studies and 199,464 biospecimens of patients from regional biobanks...
September 2012: Osong Public Health and Research Perspectives
Ahmed Khocht, Steven Schleifer, Malvin Janal, Steven Keller
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...
July 2013: Journal of the International Academy of Periodontology
Steffan T Nawrocki, Kevin R Kelly, Peter G Smith, Claudia M Espitia, Anthony Possemato, Sean A Beausoleil, Michael Milhollen, Stephen Blakemore, Michael Thomas, Allison Berger, Jennifer S Carew
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...
July 1, 2013: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Inés Prieto-Remón, Dámaso Sánchez-Carrera, Mónica López-Duarte, Carlos Richard, Carlos Pipaón
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...
November 15, 2012: Biochemical Journal
Eunice López-Muñoz, Adelina Hernández-Zarco, Normand García-Hernández, Isabel Alvarado-Cabrero, Gelasio Zarco-Espinosa, Fabio Salamanca-Gómez, Diego Arenas-Aranda
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...
August 2012: Clinical & Translational Oncology
Shuang Chen, Yun Dai, Xin-Yan Pei, Jennifer Myers, Li Wang, Lora B Kramer, Mandy Garnett, Daniella M Schwartz, Florence Su, Gary L Simmons, Justin D Richey, Dustin G Larsen, Paul Dent, Robert Z Orlowski, Steven Grant
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...
August 15, 2012: Cancer Research
Hye-Young Nam, Sung-Mi Shim, Bok-Ghee Han, Jae-Pil Jeon
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...
June 2011: Pharmacogenomics
L Bodet, E Ménoret, G Descamps, C Pellat-Deceunynck, R Bataille, S Le Gouill, P Moreau, M Amiot, P Gomez-Bougie
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...
December 7, 2010: British Journal of Cancer
Hangchan Kim, Byoung-Kee Yi, Il Kon Kim, Yun Sik Kwak
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...
August 2011: Journal of Medical Systems
Hideto Chono, Kazuya Matsumoto, Hiroshi Tsuda, Naoki Saito, Karim Lee, Sujeong Kim, Hiroaki Shibata, Naohide Ageyama, Keiji Terao, Yasuhiro Yasutomi, Junichi Mineno, Sunyoung Kim, Masayori Inouye, Ikunoshin Kato
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...
January 2011: Human Gene Therapy
Anna Isaian, Natalia V Bogdanova, Masoud Houshmand, Masoud Movahadi, Asghar Aghamohammadi, Asghar Agamohammadi, Nima Rezaei, Lida Atarod, Mahnaz Sadeghi-Shabestari, Seyed Hasan Tonekaboni, Zahra Chavoshzadeh, Seyed Mohammad Seyed Hassani, Reza Mirfakhrai, Taher Cheraghi, Najmoddin Kalantari, Mitra Ataei, Thilo Dork-Bousset, Mohammad Hossein Sanati
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...
January 2010: Journal of Clinical Immunology
Reagan M Errera, A Bourdelais, M A Drennan, E B Dodd, D W Henrichs, L Campbell
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...
February 2010: Toxicon: Official Journal of the International Society on Toxinology
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