bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1976: Monocytic/macrophagic differentiation status of human promyelocytic leukemia cells dictates targeting efficacy of NF-kappaB downstream gene productes
Authors: Vézina Amélie , Annabi Borhane 
Published: August 2012

Abstract
Disruption of the endothelial blood-brain barrier (BBB) facilitates the translocation of circulating microbes and immune cells. As a consequence, secondary cerebral infections and development of brain pathologies may occur. Enhanced transendothelial migration of HL-60-derived macrophages was recently demonstrated, but the intrinsic signalling mechanisms involved poorly documented. In this study, we investigated NF-kB signalling pathway targets associated with phorbol 12-myristate 13-acetate (PMA)-induced promyelocytic HL-60 differentiation into macrophages. Given that the inhibition of matrix metalloproteinase (MMP)-9 and of cyclooxygenase (COX)-2 limits BBB disruption, we also investigated the efficacy of the chemopreventive and dietary-derived epigallocatechin-3-gallate (EGCG) molecule on the NF-kB-mediated transcriptional regulation of a panel of 89 biomarkers including MMP-9 and COX-2. PMA-induced HL-60 cell differentiation and adhesion were reflected by IkB degradation, a signalling process that was reversible by EGCG. Using gene expression arrays, we identified moderately-to-highly expressed NF-kB gene targets associated with HL-60 differentiation process, among which EGCG was able to efficiently inhibit gene and protein MMP-9 and COX-2 expression. In contrast, EGCG was not only inefficient in reversing some PMA-induced NF-kB genes in terminally-differentiated macrophages but rather showed selective antagonism towards COX-2 expression while that of MMP-9 still remained high. Decreased expression of the 67 kDa Laminin Receptor in terminally-differentiated macrophages may contribute to such differential EGCG efficacy. Our results suggest that MMP-9-mediated BBB disruption may be prevented by EGCG only during procarcinogenic processes that trigger HL-60 macrophagic differentiation. Terminally-differentiated macrophage transendothelial migration associated to neuroinflammation may however not be pharmacologically affected by such a specific class of chemopreventive flavonoid.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1976. doi:1538-7445.AM2012-1976
Abstract 1994: Honokiol reduces drug resistance by down-regulation of survivin expression in multidrug resistant squamous cell carcinoma of the head and neck
Authors: Wang Xu , Beitler Jonathan J. , Hong Hong Wang , Lee Michael J. , Chen Zhengjia , Koenig Lydia , Amin A. R. Ruhul , Chen Zhuo (Georgia) , Arbiser Jack L. , Shin Dong M. 
Published: August 2012

Abstract
Background: Resistance to chemotherapy is a major obstacle in cancer therapy. The purpose of this study is to evaluate honokiol in combination with paclitaxel in controlling proliferation of multi-drug resistant (MDR) cancer cells. Honokiol is a small molecule purified from Magnolia officinalis. Honokiol has been shown to suppress tumor growth through apoptosis and inhibition of angiogenesis. In this study, we investigated the effects and mechanisms of those effects of honokiol on MDR squamous cell cancers of the head and neck (SCCHN) Methods: Serial MDR SCCHN lines including KB-8-5, KB-C1, and KB-V1 derived from the drug sensitive parental KB-3-1 cells were used in this study. Cytotoxic effects of honokiol alone and in combination with paclitaxel on apoptosis in drug-sensitive and -resistant cells were evaluated in vitro and in a subcutaneous KB-8-5 xenograft model, Results: The cell growth inhibition analysis revealed a wide range of IC50 values of paclitaxel from 1.66±0.09 to 6560.9 ±439.52 ng/ml in the KB serial cell lines, indicating that those cell lines have different levels of resistance to the paclitaxel treatment. In contrast, honokiol effectively inhibited proliferation and induced apoptosis in all four cell lines with IC50 values from 3.35±0.13 to 2.77±0.22 μg/ml. Mechanistic studies revealed that honokiol induced similar mitochondria-dependent apoptosis in drug resistant cell lines regardless of the differential resistance levels to paclitaxel treatment. Moreover these effects were associated with inhibition of STAT3 phosphorylation and down-regulation of STAT3 target gene expression, including survivin and Mcl-1. Combined treatment with honokiol and paclitaxel synergistically increased cytotoxicity as compared to the single drug treatment. This combination also significantly inhibited growth of xenografted tumors in nude mice. Conclusion: These results suggest that honokiol may be a promising drug in overcoming paclitaxel resistence of SCCHN. Targeting MDR SCCHN using honokiol in combination with paclitaxel, may benefit patients with SCCHN. (Supported by grants P50CA128613, GCC Distinguished Cancer Scholar to Dong M. Shin and Jonathan J Beitler)
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1994. doi:1538-7445.AM2012-1994
Abstract 2009: PKR induces apoptosis via PP2A activation and Bcl-2 dephosphorylation in IL-3 dependent murine bone marrow stem/progenitor cells
Authors: Cheng Xiaodong , Bennett Richard L. , Liu Xiangfei , May Stratford W. 
Published: August 2012

Abstract
The Interferon-induced double-stranded RNA-activated protein kinase (PKR) was originally found to be activated by viral infection leading to inhibition of new protein synthesis and apoptosis. Recently multiple studies have reported decreased expression and function of PKR in leukemia cells, although the exact role of PKR in the process of oncogenesis remains unclear. Since leukemias are clonal disorders originating in a primitive pluripotent leukemic stem cell (LSC) which is regulated by multi-potential hematopoietic growth factors including interleukin-3 (IL-3). Thus, studying how PKR regulates apoptosis in IL-3 dependent (CD123+) pluripotent stem/progenitor cells is expected to reveal PKR's role in leukemia. PKR expression was either knocked down (by 78%) using a specific ShRNA or directly inhibited (57%) by treating cells with a specific PKR inhibitor. Results revealed that inhibition of PKR was associated with a reduction of PP2A activity, a 2.3 fold increase in Bcl-2 phosphorylation and inhibition of apoptosis following treatment with 100uM hydrogen peroxide for 48 hours. In addition, okadaic acid (an inhibitor of PP2A) had a similar effect to PKR inhibition on both Bcl-2 phosphorylation (1.74 fold increase) and stress-induced apoptosis. By contrast, treatment of cells with the PP2A activator, FTY 720, resulted in decreased Bcl-2 phosphorylation (by 2.24 fold) and enhanced apoptosis in response to treatment of cells with chemotherapy (etoposide or doxorubicin) or hydrogen peroxide. To test the role of PKR in growth factor- withdrawal mediated apoptosis in bone marrow stem/progenitor cells, CD123+(IL-3R[[Unsupported Character - Symbol Font &#61537;]]+) bone marrow cells from wild type, PKR transgenic (over-expressed) and PKR null(-/-) mice were exposed to different stresses including IL-3 deprivation or hydrogen peroxide. CD123+ cells isolated from PKR null mice had a significantly lower percentage of apoptosis while CD123+ cells from PKR transgenic mice had increased apoptosis compared to cells from wild type littermate mice. These results demonstrate that PKR negatively affects hematopoietic cell survival by enhancing apoptosis following stress in a mechanism that involves PP2A activation and Bcl2 dephosphorylation. Taken together these results may indicate that inhibition of PKR's pro-apoptotic function in bone marrow pluripotent stem/progenitor cells may contribute to tumorigenesis in hematopoietic malignancies.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2009. doi:1538-7445.AM2012-2009
Abstract 2019: Investigation of cell death mediated by poly(ADP-ribose), Apoptosis-Inducing Factor (AIF) and caspases in breast cancer cells by RNA interference
Authors: Feng Xiaoxing , Proctor Alicia , Hopkins Mandi , Liu Mengwei , Koh David W. 
Published: August 2012

Abstract
Apoptosis-Inducing Factor (AIF) was previously characterized as a poly(ADP-ribose) (PAR) dependent, caspase independent cell death effector in a wide spectrum of diseases or conditions that involve cell death. The objective of this study was to determine the role of PAR and AIF in cancer cell death after chemotherapy. We have previously demonstrated the presence of AIF mediated caspase-independent cell death in MDA-MB-231 breast cancer cells following treatment with the DNA alkylating agent N-methyl-N’-nitrosoguanidine (MNNG). To gain further insight into the role of AIF in cell death induced by chemotherapy, we utilized RNA interference (RNAi) to knockdown expression of AIF and PAR glycohydrolase (PARG) in MDA-MB-231 and MCF-7 human breast cancer cells. UV-C irradiated AIF-silenced cells displayed increased cell viability. Moreover FACS analysis showed that AIF knockdown successfully protected cells against apoptosis induced by MNNG and the chemotherapeutic agents epirubicin and cyclophosphamide. Interestingly, the knockdown of PARG led to decreased apoptotic cell death after treatment with MNNG. However, inhibition of caspases using Q-VD-OPh in PARG RNAi treated cells led to an increase in apoptotic cell death, which suggests that caspase dependent cell death after chemotherapy is mediated in part by PARG. However, the knockdown of AIF in these cells led to significant protection, which indicates that cell death in the absence of caspase activity in PARG knockdown cells is mediated by AIF. Taken together, the results provide a paradigm where AIF can substitute as caspase executioner in the absence of PARG and caspases in breast cancer cells. Thus, the activation of AIF mediated cell death is a promising strategy to improve the treatment of breast cancer by providing an alternative pathway for tumor eradiation.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2019. doi:1538-7445.AM2012-2019
Abstract 2022: P53-dependent thrombocytopenia induced by the histone deacetylase inhibitor S78454
Authors: Ali Ashfaq , Bluteau Olivier , Palazzo Alberta , Boukour Siham , Lordier Larissa , Rameau Philippe , Leceluse Yann , Kraus-Berthier Laurence , Jacquet-Bescond Anne , Lelièvre Hélène , Depil Stéphane , Solary Eric , Raslova Hana , Vainchenker William , Plo Isabelle , DEBILI Najet 
Published: August 2012

Abstract
S78454 (also called PCI-24781) is an orally bioavailable, hydroxamate-based pan-HDACi currently being tested in clinical trials in the US and EU. Like many other HDACi, this drug induces a reversible thrombocytopenia. This thrombocytopenia, which was associated with a decrease in either GATA1 transcriptional activity or the expression of proteins of the Rho GTPase family (RhoA, Cdc42 or Rac), remains poorly understood. Given that the S78454 plasma level is above 100nM in treated patients, we performed a dose-response analysis (from 10 to 100 nM) of the drug effects on CFU-MK growth and cell proliferation. CFU-MKs were generated by ex vivo culture of CD34-positive cells and their differentiation was dose-dependently decreased after either a 24-hour treatment or a continuous exposure to S78454. This effect was associated with a dose-dependent decrease in MK proliferation. When added at day 8 of the culture, at a time-point when MK have nearly finished their endomitotic process and are entering in the cytoplasmic maturation step, S78454 induced a dose-dependent decrease (ten- to- two fold at 100nM and 20nM, respectively) in proplatelet formation, even when secondarily removed from the culture medium. The decreased proliferation was associated with an increased apoptosis, as demonstrated by the presence of a sub-G1 peak after propidium iodide staining, Annexin V binding, and caspase-3 proteolysis. We did not observed any blockade in the TPO/MPL/JAK2 signaling since ERK, Stat3 and Stat5 phosphorylation remained unaffected. Interestingly, MK exposed to S78454 displayed an increase in γH2AX foci formation and a decrease in Rad51 expression, a major mediator of homologous recombination, indicating a defective repair of DNA double-strand breaks. Consequently, P53 became phosphorylated in MKs, and the expression of its target genes BAX and P21 was increased. Altogether, these results suggest that S78454-induced thrombocytopenia may be mediated by induction of apoptosis in MK due to DNA-double-strand breaks and p53 activation.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2022. doi:1538-7445.AM2012-2022
Abstract 2027: Carbamylated albumin increase MMP9 activity via ERK MAPK pathway
Authors: Kim Jin Young , Park Keon Uk , Shin So Jin , Hwang Il Seon , Ha Eunyoung , Ryoo Hun-Mo 
Published: August 2012

Abstract
Objective: Carbamylation, the binding of cyanate to amino acid lysine residues, is a post-translational modification. Pathophysiological consequences of carbamylation and adverse effects of carbamylated proteins remain poorly understood. This study was designed to influence of carbamylated albumin on matrix metalloproteinase(MMP) expressions in rat mesangial cells (RMC). Methods and Results: The effect of carbamylated albumin was evaluated using zymography, Western blot analysis, MMP-9 promoter luciferase assay, and ELISA. We found that carbamylated albumin significantly increased MMP-9 productions in RMCs via stimulating MMP-9 promoter activity and ERK1/2 MAPK phosphorylation. DecreasedTIMP-1 activity by carbamylated albumin was not observed. Conclusion: We demonstrated that carbamylated albumin increased MMP-9 activity via ERK1/2MAPK mediated pathway and further studies as to the functions of carbamylated albumin will be of merit.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2027. doi:1538-7445.AM2012-2027
Abstract 2028: Krüppel-like factor 4 null mouse embryonic fibroblasts exhibit DNA repair defects post exposure to gamma-irradiation
Authors: Engda Hagos , Yang Vincent W. , Yu Bing 
Published: August 2012

Abstract
BACKGROUND: Krüppel-like factor 4 (KLF4) is a zinc finger transcription factor that exerts a potent inhibitory effect on cell cycle progression. KLF4 functions as a tumor suppressor in colorectal cancer and is involved in regulating centrosome duplication. Abnormal amplification of centrosomes has been shown to contribute to genetic instability by increasing the frequency of mitotic defects. AIM: To determine whether KLF4 is involved in maintaining genetic stability during cell division. METHODS: Mice heterozygous for the Klf4 alleles (Klf4+/−) on a C57BL/6 background were crossbred. Mouse embryonic fibroblasts (MEFs) that are wild type (Klf4+/+), heterozygous (Klf4+/−) or null (Klf4−/−) for the Klf4 alleles were derived from day-13.5 embryos. Post-senescence MEFs were derived by passing cells to senescence and maintaining them in culture until they spontaneously regained proliferative. Immuno-detection of histone variant γ-H2AX was performed to assess chromosome integrity. The levels of cell cycle regulators such as Cdk2, Cyclin E, and Cyclin D were determined by Western blotting. The presence of double strand breaks (DSB) was determined by western blot and immunofluorescence for histone variant -H2AX contains nuclear foci. Flow cytometry has been used to determine the level of DNA damage in both wildtype and klf4 null cells following gamma-irradiation. Furthermore, Expression profiles of fibroblasts isolated from mouse embryos wild type or null for the Klf4 alleles were examined by DNA microarrays. RESULTS: Cells that exhibits DSBs in their DNA can develop genomic instability, which can result in cancer formation. Compared to Klf4+/+ and Klf4−/− MEFs exposed to α-irradiation showed time-dependent increase in levels of histone variant -H2AX that persisted for up to 48 hours after the α-irradiation. On the other hand, Klf4+/+ halt cell cycle progression to allow repair of DNA damage. Western blot analysis showed that Cdk2, Cyclin E, Cyclin D and histone variant -H2AX expression were high in Klf4−/− MEFs. Furthermore, we found many of the down-regulated genes in Klf4-null MEFs encode DNA repair, and antioxidant genes. CONCLUSIONS: Results of this study demonstrate that Klf4 null mouse embryonic fibroblasts exhibit an impaired DNA damage response post gamma irradiation, when compared to wild-type cells. This data strongly suggest that the role for Klf4 in DNA damage repair in mouse embryonic fibroblast cells. These results indicate that KLF4 plays a crucial role in maintaining genetic stability and support the previous findings that KLF4 is a tumor suppressor.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2028. doi:1538-7445.AM2012-2028
Abstract 2032: A novel function of WW domain binding protein 2 (WBP2) in regulating cytoskeletal function and cellular division through binding to co-chaperone BAG3
Authors: McCollum Andrea K. , Angelos Mathew G. , Fischione Andrea D. , Mineo Marco , Kohn Elise C. 
Published: August 2012

Abstract
BAG3, a BAG co-chaperone family member, co-localizes with actin microfilaments and influences processes that involve actin function, including adhesion and migration. Because actin function regulates cell division, we hypothesized that the BAG3 WW-domain regulates cellular division through its cytoskeletal association. We show that BAG3 co-localizes with leading lamellipodia exclusively during G2 and mitosis phases. Co-immunoprecipitation of BAG3 and pulldown of GST-tagged BAG3 WW-domain confirmed that BAG3 WW-domain association with actin increased during G2 and mitosis relative to asynchronous cells. Deletion of the BAG3 WW-domain caused an abnormal cellular morphology, degenerate F-actin organization, longer doubling time (p&lt;0.05, n=4), and three-fold increase in polynucleated cells relative to empty vector and full length-BAG3 (FL-BAG3; p&lt;0.001, n=3). We confirmed polyploidy development and absence of cytokinesis in αWW-BAG3 cells by live-cell imaging, and observed mitotic delay relative to control and FL-BAG3 cells. To identify a potential regulation mechanism for BAG3-actin binding, we identified WBP2 as a novel BAG3 WW domain interacting protein in a yeast two-hybrid assay. BAG3 and WBP2 co-immunoprecipitated only in G1 and S phases, indicating cell cycle-specific BAG3-WBP2 binding. WBP2 silencing caused indiscriminate BAG3 co-immunoprecipitation with actin across all cell cycle phases, suggesting that association with WBP2 prevents BAG3-actin binding. We are the first to identify a function for WBP2, which our data show regulates BAG3 WW-domain association with actin in a cell cycle-specific manner. Because actin dysfunction has been proposed to contribute to chromosomal instability and tumor formation, the WW-domain of BAG3 is a potential target to reduce abnormal cell division.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2032. doi:1538-7445.AM2012-2032
Abstract 2048: Phosphorylation and regulation of PTEN by Polo-like kinase 1
Authors: Choi Byeong Hyeok , Lee Kyung S. , Dai Wei 
Published: August 2012

Abstract
The tumor suppressor PTEN plays a critical role in the regulation of cell survival, proliferation, and angiogenisis. Deregulated expression and/or activities frequently result in tumor development. Several recent studies have revealed that PTEN also localizes to the nucleus and that nuclear PTEN may regulate the level and activity of mitotic checkpoint proteins, thus suppressing chromosomal instability during cell division. However, the mechanism by which PTEN is translocated to the nucleus remains unclear. Given that PTEN is heavily phosphorylated and that Plk1 is an important mitotic kinase, we have asked whether Plk1 directly phosphorylates PTEN and whether Plk1-mediated phosphorylation of PTEN functions as an important regulatory mechanism during cell division. Here we report that a significant fraction of PTEN localized to nuclear chromatin. The chromatin association of PTEN was enhanced during mitosis, which was correlated with an increase in PTEN phosphorylation at threonine 366 (T366) and serine 370 (S370). Using purified recombinant proteins, we demonsatrated that Plk1 was at least partly responsible for this phosphorylation. Plk1 strongly catalyzed the incorporation of 32P into PTEN, resulting in increased signals detected by a phospho-specific antibody that recognized T366/S370 phosphorylation. Furthermore, BI-2536, a potent Plk1 inhibitor, significantly blocked PTEN phosphorylation by Plk1 in vitro, as well as its chromatin association in vivo. Combined, these results strongly suggest that Plk1 phosphorylates PTEN at T366 and/or S370 and that this phosphorylation promotes its association with chromatin during the cell cycle.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2048. doi:1538-7445.AM2012-2048