bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4069: 2-deoxyglucose and compound C reversed acidification but enhanced growth inhibition in colon cancer cells treated with metformin and phenformin
Authors: Lea Michael A. , Chako Jerel , Bolikal Sandhya , Hong Ji-Young , Chung Ryan , Ortega Andres , desBordes Charles 
Published: July 2012

Abstract
A report that effects of butyrate on some cells may be mediated by activation of AMP-dependent kinase (AMPK) prompted us to examine if other AMPK activators can induce differentiation and inhibit proliferation of colon cancer cells in a manner similar to butyrate. Using induction of alkaline phosphatase as a marker, we observed that compound C, an AMPK inhibitor, could decrease the differentiating effect of butyrate or valproate on SW1116 and Caco-2 colon cancer cells. On the other hand, A769662, an activator of AMPK did not increase alkaline phosphatase activity and decreased the induction seen with butyrate. Metformin was observed to be less effective than butyrate in the induction of alkaline phosphatase but was more effective as a growth inhibitor. Phenformin was found to be a more potent growth inhibitor than metformin and both compounds cause acidification of the medium when incubated with colon cancer cells. pH changes were monitored with a pH electrode and by the decrease in absorbance of phenol red at 560 nm. Coincubation with compound C decreased the acidification caused by the biguanides. Combined incubation of 2-deoxyglucose with either of the biguanides prevented the acidification of the medium but enhanced the growth inhibitory effects. Growth inhibitory effects of biguanides appeared less with a tetrazolium reduction assay than with thymidine incorporation but supported the conclusion that combination with 2-deoxyglucose could increase growth inhibition caused by biguanides.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4069. doi:10.1158/1538-7445.AM2011-4069
Abstract 4097: Sorafenib sensitizes solid tumors to TRAIL or TRAIL receptor agonist antibodies
Authors: Abdulghani Junaid , Allen Joshua E. , Dicker David T. , Smith Charles D. , Humphreys Robin C. , El-Deiry Wafik S. 
Published: July 2012

Abstract
Solid carcinomas display considerable resistance to chemotherapeutic drugs and tumor cell apoptosis-inducing agents such as tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced cell death. A phase III clinical trial with the multi-kinase inhibitor sorafenib (Nexavar) in Hepatoceullular carcinoma (HCC) was completed leading to the first FDA-approved drug therapy for liver cancer in 2007. Phase I/II trials have been completed with a fully-human anti-TRAIL death receptor 1 (DR4) agonist antibody (mapatumumab) in non small-cell lung carcinoma and non-Hodgkin's lymphoma and phase I trials with an anti-TRAIL-R2 (DR5) monoclonal antibody (lexatumumab) in advanced cancers. We hypothesized that sorafenib and TRAIL or sorafenib and TRAIL receptor agonist antibodies (mapatumumab or lexatumumab) may overcome resistance to apoptosis in a panel of TRAIL-resistant solid carcinoma cell lines. We observed that sorafenib induces apoptosis of HepG2 and Hep3B cells in a dose-dependent manner. In addition, sorafenib is a potent sensitizer of HCC cell lines to TRAIL. We have also found that single agent lexatumumab causes cell death in HepG2, Hep3B and SNU449 cells whereas mapatumumab does not. The combination of sorafenib with TRAIL or either TRAIL receptor agonist antibody enhances apoptosis in HCC cell lines. We found that in other solid tumor types including prostate, breast and colon cancer there is a synergistic interaction between sorafenib and TRAIL or TRAIL receptor agonist antibodies. Furthermore, these combinations prevent the growth of tumors in vivo. Sorafenib downregulates the expression of Mcl-1 protein, a member of the Bcl-2 family that has been previously found to be overexpressed in about 50% of HCC patient samples. Sorafenib was also found to inhibit Stat3 activation by Jak2 kinases. These findings suggest a molecular rationale for combining these agents in therapy of solid tumors in clinical trials.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4097. doi:10.1158/1538-7445.AM2011-4097
Abstract 411: Absence of leukotriene B4 receptor-1 promotes colon tumorigenesis in the ApcMin/+ mice by modulating gut microbiota
Authors: Jala Venkatakrishna R. , Maturu Paramahamsa , Krishnan Elangovan , Mathis Steven P. , Subbbarao Krishnaprasad , Bodduluri Sobha R. , Wang Min , Jenson Alfred B. , Proctor Mary L. , Bodduluri Haribabu 
Published: July 2012

Abstract
Leukotriene B4, a potent lipid mediator of inflammation acts through the G-protein coupled receptor, BLT1. The BLT1-/- mice displayed substantial protection in inflammatory disease models of arthritis, asthma and atherosclerosis. To examine the role of BLT1 in progression of cancers known to be promoted by inflammation, we crossed the BLT1-/- mice onto mice with a heterozygous mutation in the adenomatous polyposis coli (ApcMin/+) gene. The BLT1-/-ApcMin/+ mice demonstrated an increase in the rate of spontaneous intestinal tumor development and accelerated mortality. Unlike ApcMin/+ mice that develop mostly small intestinal tumors the BLT1-/-ApcMin/+ mice developed large colonic adenomas. Tumors from the BLT1-/-ApcMin/+ mice showed increased rates of proliferation, decrease in apoptosis and an increase in the expression of tumor promoting inflammatory markers such as TNF-α and CXCL1 and COX2 when compared to tumors from the ApcMin/+ mice. Microarray analysis of transcriptome showed that the paradoxical increase in inflammation in tumors from the BLT1-/-ApcMin/+ mice is coincidental with defective host response to infections. The expression of angiogenins, a class of antibacterial proteins was significantly reduced in tumors from BLT1-/-ApcMin/+ mice. Further, analysis of gut flora (by 16S ribosomal DNA sequences) identified major differences in microbiome colonizing the BLT1-/-ApcMin/+ and ApcMin/+ mice. BLT1-/-ApcMin/+ mice rederived and raised under germ-free conditions are completely protected from colon cancer development.
To examine the role of Toll-like receptor mediated signaling events involved in tumor promotion in the absence of BLT1, we developed BLT1/MyD88 double deficient mice. The BLT1-/-MyD88-/- mice were highly susceptible to lethal neonatal infections indicating the cooperative interactions between TLR and leukotriene pathways in host response. These BLT1-/-MyD88-/- mice could be rescued by treatment with a broad-spectrum antibiotic. The MyD88-/-ApcMin/+ mice are highly protected from intestinal cancers. The BLT1-/-MyD88-/-ApcMin/+ mice are also highly protected indicating that BLT1-mediated host defense acts upstream of MyD88-mediated tumor promoting inflammation. While both BLT1 and MyD88 are important in host defense only the MyD88 but not BLT1 activated pathways are required to initiate tumor promoting inflammation. These results identify novel roles for gut microbiota in promoting colon cancer and for BLT1 in preventing the colon cancer development by shaping the gut microbiome.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 411. doi:10.1158/1538-7445.AM2011-411
Abstract 4179: Mitochondrial DNA haplogroup M7b/c associated with the clinical outcome of OSCC in Taiwan
Authors: Hsieh Ling-Ling , Lai Chih-Husiung , Huang Shiang-Fu , Chen I-How , Liao Chun-Ta , Wang Hung-Ming 
Published: July 2012

Abstract
A large volume of studies have indicated that polymorphisms in the mitochondrial genome are associated with risk of various diseases, including cancer. However, only few studies examined the effect of polymorphisms on cancer outcome. To explore the possible role of mitochondrial polymorphisms on clinical outcome of oral squamous cell carcinomas (OSCCs) in Taiwan, whole mitochondrial genome was genotyped by DNA direct sequencing and haplogroup was defined using HaploGrep program in 305 OSCCs. One hundred and sixty-five variant sites with minor allele frequency (MAF) &gt;3 % were found in our study. Among them, 6 variant sites (1 mtLP in HVR2 and 5 SNPs at T204C, C4071T, C4850T, T16311C, T16362C) were associated with overall survival. An index score designated as the total effects of the genotypes of these 6 variant sites on survival for each individual was also developed using the estimates from the Cox model. We found that individual with the higher index score had the poorer disease-free and overall survival. In addition, an association between Asian specific haplogroup M7b/c (containing C4071T variant) and poor overall survival was observed. In conclusion, the findings provide the first evidence pointing toward mitochondrial variants affect the clinical outcome in OSCC.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4179. doi:10.1158/1538-7445.AM2011-4179
Abstract 4186: Survival time for patients with glioblastomas is highly correlated with increased expression of major mitotic checkpoint genes
Authors: Bie Li , Xia Xiao-Qin , Qiu Ji-qing , Cheng Pui , Rondeau Gaelle , Zhao Gang , McClelland Michael 
Published: July 2012

Abstract
Glioblastomas are the most common and deadly CNS neoplasms. Survival time correlates with pathological grade; most World Health Organization grade III and grade IV cases die within one year of diagnosis, whereas lower grades sometimes live for years. With the goal of optimizing objective prognostic molecular staging methods for gliomas, we examined three independent microarray datasets with a total of 6 normal, 14 grade I- II, 13 grade III and 13 grade IV gliomas, using a cross-platform analysis suite (http://www.webarraydb.org). We noticed that a number of mitotic spindle assembly checkpoint (SAC) genes had transcript levels significantly altered across different pathological grades. SAC genes ensure that accurate chromosome segregation is maintained during mitosis. Previous studies have shown failure of the mitotic spindle assembly checkpoint (SAC) leads to genomic instability and neoplastic transformation. Several studies of malignant tumor suggested that increased mRNA levels of the mitotic checkpoint correlates with tumor progression, including in breast cancer and bladder cancer. Eight major mitotic spindle checkpoint genes that had significant increases in gene expression levels with increasing glioma grade in the microarray data (p &lt; 0.001, ANOVA) were selected for quantitative reverse transcription PCR (qRT-PCR) analysis in 40 additional glioma tumors and 6 normal brain tissues; BUB1, BUB1B, BUB3, CENPE, MAD1L1, MAD2L1, CDC20, and TTK. One of these genes, CDC20, is already known to be differentially expressed across grades and inclusion allowed the relative performance of other genes to be assessed. In our study, the average mRNA transcript levels for all of these checkpoint genes increased with increasing grade. The correlations with grade had a significance level of p&lt;0.05 (ANOVA) for BUB1, BUB1B, CENPE, MAD1L1 and CDC20. Mutations or epigenetic changes in these five genes have not yet been noted to play a significant role in the causation of chromosomal instability in glioblastomas, nor in most other cancers, an exception being BUB1mutations in some cases of colorectal cancer. The consistently high level of these particular transcripts in aggressive gliomas is perhaps due to compensation for other defects in the cell machinery that would otherwise be catastrophic. Kaplan-Meier analysis showed that BUB1B and CDC20 were independent prognostic indicators for overall survival (p&lt;0.05). Further regression analysis indicated that changes in expression of BUB1B and CDC20, and perhaps CENPE, rival glioma grade as excellent prognosticators of survival.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4186. doi:10.1158/1538-7445.AM2011-4186
Abstract 4192: Role of NF-κB regulators A20 and CARD11 in middle eastern diffuse large B cell lymphoma
Authors: Abubaker Jehad , Bavi Prashant , Jehan Zeenath , Al-Haqawi Wael , Sultana Mehar , Belgaumi Sameer M. , Siraj Sarah , Ajarim Dahish , Al-Dayel Fouad , Uddin Shahab , Al-Kuraya Khawla S. 
Published: July 2012

Abstract
Aberrant NF-κB regulation has been observed in many hematopoietic malignancies including diffuse large B cell lymphoma (DLBCL). NF-κB gene plays a role in lymphomagenesis through the transcriptional activation of genes associated with cell proliferation, angiogenesis, metastasis, tumor promotion, inflammation and suppression of apoptosis. CARD11 and A20 genes are known positive and negative regulators of the NF-kB activation pathway and can alternate the NF-kB activity. Considering the potential therapeutic utility of targeting NF-kB and its key modulators, we studied CARD11 genetic alterations (mutations and amplifications), A20 mutations, and immunohistochemical expressions of A20 and CARD11 protein in 150 DLBCL samples. Incidence of CARD11 and A20 mutations was 10.7% and 15.3% of respectively. NF-kB activation was significantly associated with A20 mutation (p=0.0456) thereby highlighting the role of A20 as a tumor suppressor gene and its role in NF-kB inhibition. Interestingly, CARD11 amplification was seen in a significant proportion of the DLBCL (23%) and was linked to NFkB activation (p = 0.0111). A poor overall survival was noted in the DLBCL harboring A20 mutations (p=0.0491) and also in the DLBCL showing presence of CARD11 gene amplification (p=0.0588). Our study highlights the role of CARD11 gene amplifications as a novel mechanism for NF-kB activation and demonstrates clinico-pathological significance of CARD11 and A20 alterations in Middle Eastern DLBCL.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4192. doi:10.1158/1538-7445.AM2011-4192
Abstract 4194: Constitutive DNA-damage signaling promotes cancer cell proliferation through Chk1-CIP2A pathway independent of ATM-ATR
Authors: Khanna Anchit , Böckelman Camilla , Schreck Ilona , Weiss Carsten , Visakorpi Tapio , Ristimäki Ari , Westermarck Jukka 
Published: July 2012

Abstract
DNA damage is a hallmark of malignantly transformed cells. Accordingly, overexpression of the DNA damage activated kinases has been observed in different human cancers. However, it is unclear whether constitutive DNA damage present in unperturbed cancer cells promotes tumourigenesis.
Here we show that increased activity of DNA damage sensitive kinase Chk1 promotes proliferation of several cancer cell types by stimulating expression of CIP2A protein. Either chemical or genetic inhibition of Chk1, and not of ATM-ATR, results in potent inhibition of CIP2A protein expression levels. Importantly, Chk1 siRNA-elicited inhibition of cell proliferation and clonogenic growth is rescued by overexpression of CIP2A from a heterologous promoter. Moreover, in clinical (human) tumor samples there is a significant association between CIP2A and Chk1 expression in both ovarian and gastric cancers. Intriguingly, meta-analysis of seventeen published genome wide studies on different types of cancers unveils a striking similarity in the gene expression patterns of both CIP2A and Chk1. Amongst these, 12/17 studies show overexpression (top 10%) of both these proteins. Additionally, similarly to CIP2A, increased Chk1 expression is shown to correlate with tumor progression in human cancer.
In summary, these results identify a novel function for DNA damage kinase Chk1 in regulation of the human oncoprotein CIP2A. In general, these results provide an unprecented molecular mechanism by which constitutive DNA damage present in cancer cells promotes tumourigenesis. Additionally, as CIP2A is not significantly expressed in most of the normal human tissues, it is proposed that targeting of CIP2A might abrogate the Chk1-mediated support of proliferation without concerns related to anticancer therapy directly targeting Chk1.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4194. doi:10.1158/1538-7445.AM2011-4194
Abstract 4205: Regulation of Hif-1α expression by NADPH oxidase 5 (Nox5) in human cancer cell lines
Authors: Antony Smitha , Wu Yongzhong , Liu Han , Jiang Guojian , Juhasz Agnes , Lu Jiamo , Roy Krishnendu K. , Doroshow James H. 
Published: July 2012

Abstract
Reactive oxygen species (ROS) produced by NADPH oxidases (Noxs) participate in signaling cascades regulating proliferation. However, the relative contribution to tumor cell growth by the seven Nox homologues (Nox1-5 and Duox 1 and 2) remains unclear. Several studies have proposed that Nox5 plays a role in promoting cell proliferation in Hairy cell leukemia, Barrett's esophageal adenocarcinoma cells, and in prostate cancer; however, little is known about the signaling pathways mediated by Nox5. We explored the functional role of Nox5 in a variety of tumor cell lines, including the NCI-60 cell panel; real time RT-PCR revealed that several melanoma lines express Nox4 and Nox5, but no Nox1 mRNA; and that prostate cell lines express Nox5 mRNA. Of the Nox5- expressing NCI-60 human cancer cell lines, we studied UACC-257 melanoma and PC-3 prostate cancer cells. These lines were characterized for variations in their N-terminus Ca2+ binding domains; RT-PCR revealed that both cell lines expressed the Nox5α and Nox5γ forms. The functional role of Nox5 in UACC-257 and PC-3 cells was studied by generating stable Nox5-overexpressing clones, and by transiently silencing Nox5 that was expressed endogenously, as well as that in clones stably overexpressing Nox5. Redox-sensitive assays for both intra- and extracellular ROS production confirmed that Nox5 was functional and generated superoxide in UACC-257 and PC-3 clones overexpressing Nox5. Nox5 could be activated by the phorbol ester PMA and by the Ca2+ ionophore ionomycin in overexpressing clones. This enzymatic activity was Ca2+- and flavin dehydrogenase-dependent; the calcium chelator BAPTA-AM and the flavoprotein inhibitor DPI (200nM) significantly decreased Nox5-mediated ROS production. Overexpression of Nox5 in UACC-257 cells resulted in increased normoxic Hif-1α expression that was also Ca2+-, flavin dehydrogenase- and ROS-dependent. Silencing Nox5 by RNAi significantly inhibited both endogenous and PMA-stimulated ROS production, confirming that ROS production was Nox5-mediated. Knockdown of both endogenous and overexpressed Nox5 in both UACC-257 and PC-3 cells resulted in decreased Hif-1α expression. Studies to characterize the mechanisms by which Nox5 modulates cell proliferation through the HIF-1α pathway are ongoing. Our experiments suggest that Nox5 expression may play an important role in the generation of high local concentrations of ROS that could contribute to activation of Hif-1α and promote cell proliferation in human cancers.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4205. doi:10.1158/1538-7445.AM2011-4205
Abstract 4209: Genotoxic effects of arsenic trioxide-induced oxidative stress in human hepatocellular carcinoma (HepG2) cells
Authors: Brown Erika T. , Yedjou Clement G. , Tchounwou Paul B. 
Published: July 2012

Abstract
Recent studies in our laboratory indicated that oxidative stress plays a key role in arsenic trioxide (ATO)-induced cytotoxicity in human cancer cells. In the present investigation, we used human hepatocellular carcinoma (HepG2) cells as a model to determine whether arsenic induced DNA damage is mediated through oxidative stress. To achieve this goal, oxidative stress biomarkers were measured by lipid peroxidation, glutathione peroxidase, and catalase assays, respectively. The degree of DNA damage was estimated by the means of comet assay. The results of the lipid peroxidation showed a significant increase (p &lt;0.05) of malondialdehyde (MDA) levels with increasing ATO concentrations. Results from the glutathione peroxidase and catalase assays showed a gradual decrease in antioxidant enzyme activity in ATO-treated cells as compared the control. In regard to the comet assay, a significant increase (p &lt; 0.05) in comet tail-length and percentages of DNA cleavage were observed in ATO-treated cells using the comet assay. Taken together, our research demonstrated that oxidative stress modulates ATO mediated DNA damage in HepG2 cells.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4209. doi:10.1158/1538-7445.AM2011-4209