bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1094: MicroRNA-30a inhibits vimentin expression and as a prognostic marker in breast cancer
Authors: Chang Chia-Wei , Cheng Chun-Wen , Wang Hsiao-Wei , Chen Cheng-You , Chu Hou-Wei , Ding Shian-ling , Wang Hui-Chun , Yu Jyh-Cherng , Shen Chen-Yang 
Published: August 2012

Abstract
Recent studies have suggested a significant role of microRNAs (miRNAs) in the regulation of cancer development. This study examined whether they play a role in breast cancer progression.A miRNA microarray analysis was performed on laser-capture microdissected breast tumors of different lymph-node metastasis status showing different progression signatures, indicated by overexpression of cyclin D1 and β-catenin genes, to identify specific miRNAs that exhibit significant differences in expression. Functional interaction between the candidate miRNA (i.e. miR-30a) and the gene (i.e. Vim gene, coding for vimentin, a protein involved in epithelial-mesenchymal transition) possibly regulated by miR-30a was verified. We further examined whether decreased expression of miR-30a was associated with breast cancer progression.miR-30a negatively regulated vimentin expression, by binding to the 3′-untranslated region of Vim. Ectopic expression of miR-30a was found to suppress the migration and invasiveness phenotypes of breast cancer cell lines. More importantly, breast cancer patients with decreased miR-30a level in primary cancerous sites were found to be associated with poor clinical features (late tumor stage and lymph node metastasis) and worse progression, demonstrating an increased hazard ratio (HR) for recurrence or recurrence plus mortality during the follow-up period (P&lt;0.05). These findings provide a support of clinical importance of miR-30a in mediating breast tumor progression. Identification of miR-30a-mediated regulation of vimentin might provide a promising therapeutic target in treating breast cancer.
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 1094. doi:1538-7445.AM2012-1094
Abstract 1128: The role of peptide deformylase in the apoptosis of c-Myc overexpressing cancers
Authors: Sheth Aneesh , Escobar-Alvarez Sindy , Ran Leili , Gardner Jeffery , Scheinberg David A. 
Published: August 2012

Abstract
In prokaryotes, the removal of an N-terminal formyl group by the peptide deformylase is required for post-translational protein processing. Our identification of human mitochondrial PDF (HsPDF) and deformylated peptides in the mitochondria shows that a similar post-translational processing of the 13 human mitochondrial DNA-encoded, and formylated, proteins can occur. Inhibition of HsPDF reduced proliferation of many human cancer lines. We developed a monoclonal antibody to hsPDF; profiling of cancer and normal cell lines by three immunoassays, flow cytometry, immunoprecipitation and in-cell western, showed over-expression of HsPDF in cancer cell lines. This data was confirmed at the mRNA level by RT-PCR. As the c-myc oncogene regulates mitochondria and metabolism in cancer, we investigated its role in regulating HsPDF. In a tet-off c-myc cell line, the expression of HsPDF was regulated by c-myc; inhibiting this protein resulted in the selective inhibition of mitochondrial protein translation, and eventual death of myc-positive, but not myc-negative cells. Furthmore, knocking down c-myc in a Burkitt's Lymphoma cell line significantly reduced the expression of both the mRNA and the protein levels of HsPDF relative to beta-Actin. The mechanism of death by actinonin was apoptosis in two c-myc over-expressing cell lines. Death was initiated with mitochondrial membrane depolarization, followed by inhibition of mitochondrial translation, and eventually caspase-3 activation and apoptosis. To confirm the specificity of PDF in cell death, we used two other hydroxamic acid peptidomimetics that do not target HsPDF. These compounds did not result in apoptotic death. Furthermore, inhibition of translation of the mitochondrial DNA by chloramphenicol and tetracycline, two structurally different inhibitors of the mitochondrial ribosome, which is upstream of deformylation, followed by treatment with actinonin resulted in a delay and marked reduction in apoptosis by actinonin, but not by staurosporine and the HDAC inhibitors SAHA and Trichostatin A. Thus, death was not a result of ATP depletion, but a unique PDF-mediated mechanism.
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 1128. doi:1538-7445.AM2012-1128
Abstract 1132: Regulation of the glutamine-to-lipid pathway by HIF: Reductive TCA cycle is a metabolic signature of VHL deficiency
Authors: Yang Juanjuan , Gameiro Paulo A. , Stephanopoulos Gregory , Iliopoulos Othon 
Published: August 2012

Abstract
Cancer cells undergo fundamental changes in glucose and glutamine metabolism to support anabolic processes. Acetyl-CoA is a central precursor for lipid synthesis, being generated from glucose-derived citrate in well oxygenated cells. Cells exposed to hypoxia divert glucose to lactate, raising the question of how TCA cycle is maintained to support lipogenesis. We recently showed that, under hypoxia conditions, cancer cells primarily utilize glutamine for lipid synthesis through reductive TCA cycle (redTCA). To investigate the regulation of this metabolic switch, we studied the role of Hypoxia Inducible Factors (HIF1s) in renal cell carcinoma (RCC) cell lines that are deficient in the von Hippel-Lindau (VHL) tumor suppressor gene. These cells exhibit constitutive HIF activity irrespective of oxygen availability. Here, we show that loss-of-VHL engages RCC cells in redTCA even under normoxia conditions in a HIF-dependent manner. Reintroduction of VHL restores the glucose-to-lipid flux. Inactivation of HIF regulatory subunits dramatically attenuates redTCA in RCC cell lines. Inversely, exogenous expression of a VHL-insensitive HIF2α mutant (P564toA) in VHL proficient cell lines is sufficient to stimulate redTCA cycle and lipogenesis from glutamine, under conditions of normoxia. Importantly, loss of VHL rendered RCC cells sensitive to glutamine restriction. VHL-deficient RCC cells grow less than their VHL-replete isogenic counterparts when cultured under conditions of low glutamine availability. Our results elucidate the metabolic control of lipogenesis by the VHL-HIF signaling pathway and highlight novel therapeutic targets for RCC and HIF-overexpressing tumors.
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 1132. doi:1538-7445.AM2012-1132
Abstract 1149: The expression of Ki-67, but not IGF1R, predicts a poor disease-free survival in patients with adenocarcinoma of the lung
Authors: Oka Soichi , Uramoto Hidetaka , Chikaishi Yasuhiro , Nakagawa Makoto , Shimokawa Hidehiko , Takenaka Masaru , Shigematu Yoshiki , So Tomoko , Hanagiri Takeshi , Tanaka Fumihiro 
Published: August 2012

Abstract
Background: Ki-67 expression has been established as a predictive marker for recurrence in breast cancer. The insulin-like growth factor 1 receptor (IGF1R) is a transmembrane heterotetrameric protein implicated in promoting the oncogenic transformation, growth and survival of cancer cells. However, no useful data are presently available regarding the biological significance of both molecules in lung cancer. Therefore, we investigated the relationship between the expression of Ki-67 and IGF1R. This is the first molecular analysis of the correlation between the expression of Ki-67 and IGF1R in a Japanese population of primary lung adenocarcinoma patients. Methods: Tumor specimens were collected from 183 consecutive patients who underwent a complete resection for lung adenocarcinoma from 2003 to 2007 in our department. We analyzed the Ki-67 and IGF1R expression levels in the primary lung adenocarcinomas by immunohistochemistry. Results: The positive expression of Ki-67 and IGF1R was identified in 41 (22.4%) and 43 (23.6%) patients, respectively. The positive expression of Ki-67 was identified in 14 (50.0%) of 28 patients and 27 (18.1%) of 155 patients with and without recurrence, respectively (p&lt; 0.001). The positive expression of Ki-67 was associated with a poorer disease-free survival (DFS) according to the survival analysis. A multivariate analysis also demonstrated that Ki-67 expression was independently associated with an increased risk of a poor DFS. On the other hand, a significant relationship was also observed between the expression levels of Ki-67 and IGF1R in NSCLC. However, in the subgroup analysis, no significant correlation was not observed. Conclusions: The expression of Ki-67, but not IGF1R, may be a useful marker for predicting postoperative recurrence in patients with the primary lung adenocarcinoma following complete resection.
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 1149. doi:1538-7445.AM2012-1149
Abstract 1150: Genome-wide DNA methylation profiling of cell-free serum DNA in esophageal adenocarcinoma and Barrett's esophagus
Authors: Zhai Rihong , Zhao Yang , Su Li , Carssidy Lauren , Liu Geoffrey , Christiani David 
Published: August 2012

Abstract
Aberrant DNA methylation (DNAm) is a feature of most types of cancers. Genome-wide DNAm profiling has been performed successfully on DNA extracted from many types of tumor tissues. However, the invasive procedure and the likely existence of tissue heterogeneity limit the utility of tumor tissue for epidemiological studies. While recent data indicate that cell-free circulating DNA methylation (cfDNAm) profiles reflect DNAm profiles in matched tumor tissues, no studies have examined the association of cfDNAm with cancer or precursors on a genome-wide scale. The objective of this pilot study was to evaluate the putative significance of genome-wide cfDNAm profiles in esophageal adenocarcinoma (EA) and Barrett's esophagus (BE, EA precursor). We performed genome-wide DNAm profiling in EA tissue DNA (n=8) and matched serum DNA (n=8), in serum DNAs of BE (n=12) and healthy controls (n=12), using the Infinium Humanmethylation27 Beadchip that covers 27,578 CpG loci in 14,495 genes. We found that cfDNAm profiles were highly correlated to DNAm profiles in matched tumor tissue DNAs (r=0.92) in patients with EA. We selected the most differentially methylated loci (a β-value difference of &gt;0.2 and a P-value of 6 x 10 −7 between groups) to perform hierarchical clustering analysis. We found that 911 loci can perfectly discriminate between EA and control samples; 554 loci can separate EA from BE samples; and 46 loci can distinguish BE from control samples. These results suggest that genome-wide cfDNAm profiles are highly consistent with DNAm profiles detected in corresponding tumor tissues. Differential cfDNAm profiling may be a useful approach for the non-invasive screening of EA and EA premalignant lesions. Supported by grants: Flight Attendant Medical Research Institute (FAMRI) grant# 062459; NIH grants CA92824, CA74386, CA90578, and CA119650); the Kevin Jackson Memorial Fund and Alan Brown Chair of Molecular Genomics.
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 1150. doi:1538-7445.AM2012-1150
Abstract 1156: Cell-surface marker discovery for colorectal cancer
Authors: Sewda Kamini , Wojtkowiak Jonathan W. , Enkemann Steven , Lopez Alexis S. , Coppola Domenico , Shibata David , Yeatman Timothy J. , Gillies Robert J. , Morse David L. 
Published: August 2012

Abstract
In the United States and Europe, colorectal cancer (CRC) has the second highest mortality rate of all cancers. Early diagnosis allows for treatment and improved survival. Currently, colonoscopy is the standard of care for detection of early-stage CRC, which is an invasive procedure that requires a cathartic bowel preparation and general anesthesia. Consequently, less invasive screening methods are highly desirable. The objective of this study is to develop a targeted molecular imaging technique termed “molecular colonography,” that can non-invasively detect dysplastic and neoplastic colonic lesions with high sensitivity and conspicuity by oral administration of ligand-targeted probes containing image contrast agents followed by clearance and non-invasive colonography with MRI, CT or Fluorescence imaging. The first step in the development of molecular colonography is identification of cell-surface markers for CRC. To accomplish this goal, gene expression profiling of DNA microarray data from 432 adenocarcinomas, 39 adenomas and 16 inflammatory bowel disease; and unaffected patient tissue samples (178 colon, 6 small intestine, 4 stomach, 4 esophagus, 4 trachea, 3 oral mucosa and 3 tonsil) was performed. Data were filtered using a previously compiled list of 3,800 cell surface genes from the NCBI Gene Expression Omnibus database. Of these, 1085 genes were broadly expressed in CRC and were ranked by differential expression in adenomas and adenocarcinomas vs. normal tissues. Six cell-surface markers were identified that are highly and broadly expressed as mRNA in adenomas and adenocarcinomas relative to unaffected tissues: TLR4, GPR56, GRM8, LY6G6D, CLDN1 and SLC01B3. TLR4 and/or GRM8 were shown to be expressed in 100% of the colon adenomas and adenocarcinomas in this dataset. To confirm protein expression, immunohistochemistry of normal (n=15) and CRC (16 adenoma and 60 adenocarcinoma) patient tissue samples and 26 CRC cell lines was performed. All six markers were highly and broadly expressed in adenomas and adenocarcinomas compared to normal colon. Further validations by mRNA (qRT-PCR) and protein expression (Western blot and immunocytochemistry) of these markers were also performed in nine colon tumor cell lines (COLO-205, DIFI, HCT15, HCT116, HT-29, KM12C, Km12SM, SW480 and SW620). Development of specific binding ligands for selected targets is underway.
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 1156. doi:1538-7445.AM2012-1156
Abstract 1158: Clinical significance of p53 codon 72 polymorphism in hepatocellular carcinomas
Authors: Council Leona N. , Shanmugam Chandrakumar , Katkoori Venkat R. , Sthanam Meenakshi , Hanna Alex , Manne Upender 
Published: August 2012

Abstract
Purpose: We recently demonstrated that, in colorectal carcinomas, the presence of a single nucleotide polymorphism (SNP) at codon 72 of the p53 gene was associated with a poor outcome for African American (AA) patients. Since such studies have not been performed for hepatocellular carcinomas (HCCs), we determined, for AAs and non-Hispanic Caucasians (NHCAs), the prevalence of p53 SNPs in codon 72 of HCCs and its association with adverse clinical and pathological features. Methods: DNA samples extracted from 48 archived, formalin-fixed, paraffin-embedded HCC tissues and from matching, uninvolved liver were analyzed for the mutational status of the p53 gene by sequencing exon 4 through exon 9. The results obtained were correlated with the demographic and clinicopathological features of the HCCs and with patient survival. Results: Overall, the frequency of missense point mutations in p53 of HCCs was low (6 of 48, 12%). Missense point mutations, however, were common in NHCAs (4 of 6). Genotyping of codon 72 of p53 demonstrated that the Arg/Arg phenotype had the highest frequency (27 of 48; 56%), followed by Arg/Pro (16 of 48; 33%) and Pro/Pro (5 of 48; 11%). Four of five patients with the Pro/Pro phenotype were AAs (χ2 p = 0.028). Of these, three of the four tumors had high proliferative (ki67) indices; two of the four were poorly differentiated. In contrast, poorly differentiated tumors were few in Arg/Arg (1 of 27, 4%) and Arg/Pro (1 of 16; 6%) (χ2p = 0.016) phenotype groups. For all patients, the Pro/Pro phenotype were associated with hepatitis C virus (HCV) infection (χ2 p = 0.048). Furthermore, AAs with the Pro/Pro phenotype had lower median survival (15.5 months) compared to those with the Arg/Arg and Arg/Pro (32 months) phenotypes. NHCA patients with missense point mutations had shorter median survival (22.5 months) relative to NHCAs with wild-type p53 (34 months).Conclusion: These preliminary findings suggest that, in AAs, the Pro/Pro phenotype at codon 72 of the p53 gene is associated with aggressive tumor behavior, shorter median survival, and HCV infection. These pilot studies were supported jointly by a Charles Barkley Award through the UAB Minority Health Disparities Research Center (MHRC) and the UAB Center for Clinical and Translational Science (5UL1 RR025777-04).
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 1158. doi:1538-7445.AM2012-1158
Abstract 1321: A novel prevention method against re-obstruction of titanium alloy stent for biliary malignancy using generation of hydroxyl radical under ultrasonic irradiation
Authors: Fujimura Tomonori , Itano Osamu , Matsuda Sachiko , Tatsuya Onishi , Kitago Minoru , Shinoda Masahiro , kawachi Shigeyuki , Tanabe Minoru , Ogino Chiaki , Shimizu Nobuaki , Kitagawa Yuko 
Published: August 2012

Abstract
[introduction] Palliative biliary drainage using a metallic stent is performed for biliary obstruction by unresectable biliary carcinoma.The most important problem of biliary stenting therapy is re-obstruction due to tumor ingrowth. The generation of hydroxyl radical was investigated during ultrasonic irradiation and in the presence of TiO2(Shimizu, etal.Ultrason.Sonochem.2008).The metal stent which is used for biliary drainage is made of titanium alloy, and it is thought that it could generate hydroxyl radicals under ultrasonic irradiation in the same way. The object of this study was to establish a novel prevention method of re-obstruction of the stent using generation of hydroxyl radical under ultrasonic irradiation. [method] {in vitro}Nickel titanium alloy was ultrasonically irradiated at frequency of 1MHz for 30 seconds and the amount of generated hydroxyl radical was measured when intensity was changed to 0.1-0.5 W/cm2 by APF method. To evaluate the cytotoxic effect of the generated radicals, trypan blue exclusion assay was used.The number of living cells were counted. {in vivo}A stent re-obstruction model was established.Nude mice(BALB c nu/nu) were given an injection of 1.0×107 of human squamous carcinoma A431 cells on the back.After Seven days, a stent was put in the neighborhood of tumor.The irradiation group(n=3) was given 10 minutes-ultrasonic irradiation of 0.3W /cm2 once a day.The non-irradiation group(n=3) was not irradiated. Tumors with stents were resected on the 14th day. Tumor ingrowth area was measured and histlogical examination of the tumors was performed. [result] {in vitro}The maximum amount of hydroxyl radical generation was measured under ultrasonic irradiation of 0.3W /cm2. The number of living cells with titanium alloy under ultrasonic irradiation(0.3W /cm2 30seconds) was 79% of that without ultrasonic irradiation. {in vivo}On the 14th day, tumor ingrowth to the stent was seen in the non-irradiation group of the stent re-obstruction model.Tumor ingrowth to the stent was clearly inhibited in the irradiation group. [conclusion] Hydroxyl radical was generated from a titanium alloy stent by ultrasonic irradiation and seemed to have therapeutic efficacy. Tumor ingrowth was inhibited, and preventive effect against re-obstruction was suggested.
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 1321. doi:1538-7445.AM2012-1321
Abstract 1324: Unraveling novel functions of the oncogene Astrocyte elevated gene-1 (AEG-1) contributing to hepatocarcinogenesis employing a transgenic mouse model
Authors: Srivastava Jyoti , Siddiq Ayesha , Emdad Luni , Santhekadur Prasanna Kumar , Chen Dong , Gredler Rachel , Shen Xue-Ning , Robertson Chadia L. , Stafflinger Jillian , Subler Mark A. , Dumur Catherine I. , Hylemon Phillip B. , Windle Jolene J. , Fisher Paul B. , Sarkar Devanand 
Published: August 2012

Abstract
In vitro tissue culture and nude mice xenograft models have firmly established the role of Astrocyte elevated gene-1 (AEG-1) as a positive regulator of tumorigenesis, including hepatocarcinogenesis. To better appreciate the role of AEG-1 in hepatocarcinogenesis and to dissect the underlying molecular mechanism, we have created a transgenic mouse with hepatocyte-specific expression of AEG-1 (Alb/AEG1). Wild-type (WT) and Alb/AEG-1 mice were challenged with a hepatocarcinogen, N-nitrosodiethylamine (DEN), at 2 weeks of age. At 28 weeks of age, Alb/AEG-1 mice, but not WT mice, developed multinodular HCC with steatotic features and highly elevated serum liver enzymes. Affymetrix microarray analyses identified modulation of expression of genes associated with invasion, metastasis, angiogenesis and fatty acid synthesis in DEN-treated Alb/AEG-1 mice versus their WT counterparts. Hepatocytes isolated from Alb/AEG-1 mice demonstrated profound chemoresistance and dramatically evaded reduction in cell viability upon growth factor deprivation, which was associated with activation of multiple pro-survival signaling pathways. Compared to the WT hepatocytes, Alb/AEG-1 hepatocytes demonstrated marked resistance towards senescence, which was associated with abrogation of activation of a DNA damage response. Conditioned media (CM) from Alb/AEG-1 hepatocytes, but not form WT hepatocytes, induced marked angiogenesis. Mass spectrometric analysis of CM revealed noticeable increases in coagulation factors by AEG-1, which are known to play a significant role in regulating tumor invasion, angiogenesis and metastasis. siRNA-mediated knockdown of coagulation factor XII resulted in profound inhibition of AEG-1-induced angiogenesis. Our studies reveal novel aspects of AEG-1 functions, such as induction of steatosis, inhibition of senescence, a known anti-cancer mechanism, and activation of coagulation pathway to augment an aggressive hepatocarcinogenic phenotype. The Alb/AEG-1 mouse will be a useful model to decipher AEG-1 function in the context of hepatocarcinogenesis and to evaluate the efficacy of novel therapeutic strategies directed towards HCC.
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 1324. doi:1538-7445.AM2012-1324