bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3871: Expression of MACC1, a metastasis-related protein, associated with the progression of colorectal cancer
Authors: Ashktorab Hassan , Herrmann Pia , Lee Edward L. , Razjouan Hadi , Green William , Smoot Duane T. , Brim Hassan , Stein Ulrike 
Published: June 2012

Abstract
Background: Colorectal cancer (CRC) as the second most common cancer in western world has different prognostic basis in contrast to other cancers. Its pathologic staging is the main prognostic factor. Recently, MACC1 has been proposed as an effective marker for identifying patients at high risk for the development of distant metastases when MACC1 is highly expressed in the not (yet) metastasized primary tumor.
Aims and Methods: We aimed to assess the cellular and sub-cellular expression of MACC1 in age matched normal, adenomatous and cancerous colonic tissue samples. Samples were recruited from pathology department of Howard University Hospital. The Tissue Micro Array (TMA) sections were made from all duplicated samples and put in three different TMA slides as normal matched (n=44), adenomatous (n=60) and adenocarcinoma (n=36). Total of 140 samples were stained for MACC1 by Immuno-Histo-Chemistry method. Then, all three TMA were read by two pathologists including one GI pathologist. The expression were reported as staining 0, 1, 2, 3, 4 which refer to none, less than 10%, 10-25%, 25-50%, 50-75%, &gt;75%, respectively. Sub-cellular staining was reported as nuclear, cytoplasmic, or both.
Results: Of 140 samples, 36 were adenocarcinomas (mean age: 64.3; M/F: 16/20); 60 adenomatous (mean age: 64.8; M/F: 31/29); 44 normal controls (mean age 65.8; M/F: 22/22). Adenocarcinomas received score 4 in 86.1% of cases which was significantly higher (p&lt;0.05) than normal (15.9%) and adenomatous (28.3%) cases. MACC1 stained more in cytoplasm (88.6%) in contrast to normal (44.7%) and adenomatous cases (32.1%) with P &lt; 0.05. Observationally, high grade adenomas had higher scores (3 or 4) than low grade ones (P=0.1). Of total 18 patients with stage 3 and/or 4, 14 scored 4 and had cytoplasmic stainning.
Conclusions: Our data showed that MACC1 not only can be a prognostic and pathological marker to differentiate high grade from low grade adenoma.
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 3871. doi:10.1158/1538-7445.AM2011-3871
Abstract 39: A mathematical model for the dependence on tumor size of the rate of metastasis formation
Authors: El-Kareh Ardith W. , Secomb Timothy W. 
Published: June 2012

Abstract
That the dependence of the rate of formation of new metastases on the existing tumor volume is weak has been demonstrated from data on the distribution of sizes of metastasic lesions, as well as data on the fraction of tumors that are metastatic as a function of tumor size at diagnosis. A mathematical model for the rate of metastasis formation as a function of tumor size was developed to explain this finding and is presented here. The model includes several stromal cell populations, in particular macrophages and fibroblasts, in addition to tumor cells, which are divided into epithelial- and mesenchymal-like populations. Epithelial-to-mesenchymal transitions are accounted for, as well as key growth factors that mediate tumor-stroma crosstalk and recruitment of stromal cells to the tumor mass. A key feature of the model is cooperativity in the steps involved in the establishment of metastases. Experimental findings of tumor cell-macrophage cooperativity in chemotaxis-driven migration towards microvessels, and EMT/non-EMT cooperativity in tumor cell escape, extravasation and intravasation are incorporated into the model. By involving the product of two or more rates, each of which depend on tumor volume raised to a power less than one, these cooperative processes result in a dependence of the metastatic rate on tumor size that is less than the 2/3 power expected if the rate were merely surface-area dependent. In addition to providing a framework for understanding experimental findings on the kinetics of metastasis, the model should prove useful for investigating the interplay between cell kill rates due to treatment and tumor regrowth kinetics in the most common case where the treated tumor consists of a distribution of metastatic lesions rather than a single mass.
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 39. doi:10.1158/1538-7445.AM2011-39
Abstract 3964: In colorectal cancer cells, the beta-catenin/TCF complex regulates several growth suppressive microRNAs that target cancer promoting genes
Authors: Schepeler Troels , Holm Anja , Halvey Patrick , Nordentoft Iver , Lamy Philippe , Christensen Lise Lotte , Thorsen Kasper , Liebler Daniel C. , Ørntoft Torben F. , Andersen Claus L. 
Published: June 2012

Abstract
Aberrant activation of the Wnt signaling pathway is causally involved in the formation of most colorectal cancers (CRCs). Whereas detailed knowledge exists regarding Wnt regulated protein coding genes, much less is known about the possible involvement of non-coding RNAs. Here we used TaqMan Array MicroRNA Cards, capable of detecting 664 unique human microRNAs (miRNAs), to describe changes of the miRNA transcriptome following disruption of beta-catenin/TCF4 activity in DLD1 CRC cells. Most miRNAs appeared to respond independently of host gene regulation and proximal TCF4 chromatin occupancy. A module of miRNAs suppressed by Wnt signaling in vitro was downregulated in a series of human primary CRCs (n = 46), and CRC cell lines (n = 7), relative to normal adjacent mucosa (n = 14). Several of these miRNAs (miR-145, miR-126, miR-30e-3p, and miR-139-5p) markedly inhibited CRC cell growth in vitro when ectopically expressed. By using an integrative approach of proteomics and microarrays, together interrogating thousands of proteins and genome-wide mRNA levels, we also provide detailed insight into the target gene network controlled by miR-30e-3p. Specifically HELZ and PIK3C2A were directly repressed via several functional seed matching binding motifs located within the transcripts. siRNA-mediated silencing of PIK3C2A partly phenocopied the growth suppressive phenotype of miR-30e-3p suggesting that miR-30e-3p restricts CRC cell growth in part by targeting PIK3C2A. Collectively, our study demonstrates that multiple miRNAs are upregulated as a consequence of forced attenuation of Wnt signaling in CRC cells, and some of these miRNAs inhibit cell growth, possibly through repression of several growth stimulatory cancer-related genes.
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 3964. doi:10.1158/1538-7445.AM2011-3964
Abstract 3968: MicroRNA-34a inhibits proliferation and invasion by targeting c-Myc in prostate cancer cells
Authors: Yamamura Soichiro , Saini Sharanjot , Majid Shahana , Hirata Hiroshi , Ueno Koji , Deng Guoren , Tanaka Yuichiro , Carroll Peter , Dahiya Rajvir 
Published: June 2012

Abstract
MicroRNA-34a (miR-34a), a potent p53 mediator, has been reported to function as a tumor suppressor. The proto-oncogene c-Myc regulates cell proliferation and transformation both transcriptionally and non-transcriptionally and is frequently deregulated in human cancers. Rho GTPases are small G proteins that regulate various cellular processes, including cytoskeletal dynamics, migration, cell proliferation, apoptosis, and transcription. RhoA has been shown to control cancer metastasis and progression and cross-talk between RhoA and c-Myc has been reported. We studied the functional effects of miR-34a on c-Myc and RhoA in PC-3 prostate cancer cells. Transfection of miR-34a into PC-3 cells strongly inhibited in vitro cell proliferation, in vivo xenograft growth and cell invasion and promoted apoptosis. miR-34a downregulated expression of c-Myc by targeting its 3’ UTR as shown by luciferase reporter assays. miR-34a was also found to repress RhoA expression. Overexpression of c-Myc reversed miR-34a suppression of RhoA expression and invasion, suggesting that miR-34a inhibits invasion by suppressing RhoA through c-Myc. We also found that miR-34a downregulated guanine nucleotide exchange factors (GEFs) which convert inactive GTPases to an active form. Our results demonstrate that miR-34a suppresses malignancy by targeting c-Myc in PC-3 prostate cancer 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 3968. doi:10.1158/1538-7445.AM2011-3968
Abstract 3978: DDX20, a suppressor of hepatocarcinogenesis, controls NF-κB activity through regulating the function of miRNA-22 and miRNA-140-3p targeting transcriptional coactivators
Authors: Takata Akemi , Otsuka Motoyuki , Kojima Kentaro , Yoshikawa Takeshi , Kishikawa Takahiro , Ijichi Hideaki , Hirata Yoshihiro , Tateishi Keisuke , Yoshida Haruhiko , Omata Masao , Koike Kazuhiko 
Published: June 2012

Abstract
MiRNA expression profile of human cancers has been characterized by an overall miRNA downregulation. While the causes include a transcriptional silencing and a failure of miRNA maturation, another possibility is that the deregulation of the machinery components for executing miRNA function also may cause similar consequences. Then, we screened the protein expression levels of the established members of the miRNA-containing ribonucleoproteins (Dicer, Ago2, TRBP2, DDX20 also known as Gemin3, and Gemin4) in various organ cancers by immunohisotchemistry. We detected reduced expression of DDX20 only in hepatocellular carcinoma tissues, while the levels of other genes were not drastically changed. We show that DDX20 suppresses NF-κB activity through regulating a subset of miRNA function. A microRNA library screen revealed that miR-140-3p and miR-22 suppress NF-κB activation by targeting the expression of NRIP1 and NCOA1, both are coactivators of NF-κB. However, in DDX20 deficient cells, this suppressive effect was lost, leading to NF-κB activation, a key regulator of hepatocarcinogenesis. In addition, DDX20 knockdown indeed induced cell transformation, revealed by a sphere-forming assay. These results indicate that DDX20 deficiency enhances NF-κB activity by impairing the NF-κB-suppressive action of microRNAs, and suggest that deregulation of the microRNA machinery may be one of the mechanisms of oncogenesis in liver 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 3978. doi:10.1158/1538-7445.AM2011-3978
Abstract 398: Interleukin 6 may predict chemoresistant ovarian cancer
Authors: Kerr Elizabeth H. , Oelschlager Denise K. , McNally Lacey R. , Grizzle William E. 
Published: June 2012

Abstract
Interleukin 6 (IL-6) has been hypothesized to facilitate the growth and progression of some malignancies by increasing angiogenesis. The aim of this study was to evaluate ovarian ascites from chemotherapy-naïve ovarian cancer patients and determine whether cytokines including IL-6 could predict resistance.
After IRB approval, patient ascites and metastatic implants were collected. The metastatic implants were evaluated for platinum sensitivity by treatment with 50 uM carboplatin for 48 hours and then cell viability was analyzed. The cells were removed by centrifugation from the ascites fluid and expression of IL-6, IL-1a, IL-1ra, IL-8, VEGF, and RANTES was evaluated in the fluid and lysed cells separately using a Millipore Custom Magnetic Bead Kit (Millipore, Billerica, MA) on a Bio-Plex Cytokine Assay (Bio-Rad Laboratories, Hercules, CA).
Twelve patients with advanced stage ovarian papillary serous carcinoma undergoing primary cytoreductive surgery had ascites samples which were adequate for analysis. Six patients were platinum sensitive and 6 patients were platinum resistant. IL-6 levels in the acellular fluid correlated with chemoresistance (P = 0.05). IL-1a and IL-1ra levels tended to be associated with chemoresistance (P = 0.22; P = 0.1) while IL-8 and VEGF levels tended to be associated with chemosensitivity (P = 0.23; P = 0.16). RANTES showed no association with either chemoresistance or chemosensitivity. Levels of cytokines extracted from the cells were low and did not impact the results of analysis of the cytokines. We conclude that levels of IL-6 in ascites may indicate platinum resistance.
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 398. doi:10.1158/1538-7445.AM2011-398
Abstract 3983: MiR-31 isoforms differentially regulate expression of dicer in cancer cells
Authors: Chan Yu-Tzu , Lin You-Chin , Lin Ruey-Jen , Kuo Huan-Hsien , Chiu Kuo Ping , Yu Alice L. 
Published: June 2012

Abstract
MicroRNAs (miRNAs) are a group of small non-coding RNAs involved in several important biological processes. Recent studies have implied that imprecise cleavage of primary or precursor RNA by Drosha or Dicer respectively could produce miRNAs with variations at 5’-and/or 3’-ends, which were termed “isomiR”. The existence of isomiRs may increase the complexity of miRNA biology, although their functions have not been explored. This is further complicated by the observation of variations in the population of isomer for a given miRNA among different species as well as among different types of cells within the same species (human cells), which raises the issue whether these isomers might exert differential effects on target gene regulation. Here, we utilized three miR-31 isoforms (miR-31-H, miR-31-P, and miR-31-M) which differ from each other only slightly in their sequences at both ends, to compare their capacity to regulate a predicted target, Dicer. Interestingly, we found only miR-31-P was able to directly repress Dicer expression in both breast cancer MCF-7 cells and lung cancer A549 cells, resulting in their enhanced sensitivity to cisplatin, which is known to be associated with Dicer knockdown. In line with this, the amount of miR-31-P bound to the RNA-induced silencing complex (RISC) was greater than that of miR-31-H and -M by RNA-CHIP analysis. Furthermore, evaluation of other known miR-31 target genes showed that expression of some target genes was indeed differentially regulated by miR-31 isoforms. Our findings not only revealed Dicer to be a direct target of miR-31, but also demonstrated the disparate functions of isomiRs for the fist time, providing a novel functional mechanism of fine-tuning of gene expression by miRNAs.
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 3983. doi:10.1158/1538-7445.AM2011-3983
Abstract 399: Elevation of angiopoietin-like protein 4 by PGE2 and hypoxia promotes colorectal cancer progression
Authors: Kim Sun-Hee , Park Yun-Yong , Kim Sang-Wook , Lee Ju-Seog , Wang Dingzhi , DuBois Raymond N. 
Published: June 2012

Abstract
Prostaglandin E2 (PGE2), the most abundant COX-2-derived prostaglandin found in colorectal cancers, promotes tumor cell proliferation and survival via multiple signaling pathways. However, the role of PGE2 in tumor hypoxia is not well understood. Here, we show that a synergistic effect of PGE2 and hypoxia on enhancing ANGPTL4 expression and that elevation of ANGPTL4 promotes colorectal cancer progression. PGE2 induces ANGPTL4 expression at both the mRNA and protein levels under hypoxic conditions. Moreover, hypoxia induces one of the prostaglandin receptors, known as EP1. Activation of EP1 enhances ANGPTL4 expression, whereas blockage of EP1 by its antagonist inhibits PGE2 induction of ANGPTL4 under hypoxic conditions. Over-expression of ANGPTL4 promotes cell proliferation and tumor growth in vivo. In addition, treatment with ANGPTL4 recombinant protein increases cancer cell proliferation through stimulating STAT1 activation. These findings are relevant to human disease since we found that the expression of ANGPTL4 and STAT1 are elevated in 50% of human colorectal cancers and there is a positive correlation between COX-2 and ANGPTL4 as well STAT1 expression in the specimens tested. These results indicate that PGE2 plays an important role in promoting cancer cellular adaptive response to hypoxia and cancer progression via ANGPTL4.
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 399. doi:10.1158/1538-7445.AM2011-399
Abstract 3992: Roles of ASH1-miR-375 pathway in development of lung cancers with neuroendocrine features
Authors: Hirotaka Osada , Nishikawa Eri , Arima Chinatsu , Okazaki Yasumasa , Tomida Shuta , Tatematsu Yoshio , Taguchi Ayumu , Shimada Yukako , Yanagisawa Kiyoshi , Toyokuni Shinya , Sekido Yoshitaka , Takahashi Takashi 
Published: June 2012

Abstract
Lung cancers with neuroendocrine (NE) features are often very aggressive, though the underlying molecular mechanisms have not been clearly elucidated. We previously reported that the basic helix-loop-helix protein, achaete-scute homologue 1 (ASH1/ASCL1), a master regulator of pulmonary neuroendocrine cell development, is crucially involved in the pathogenesis of lung cancers with neuroendocrine features (NE-lung cancers). In the present study, we searched for miRNAs regulated by ASH1 in order to gain insight into the involvement of miRNAs downstream of ASH1 in NE-lung cancer pathogenesis. We consequently found that introduction of ASH1 into A549 cells markedly induced miR-375 and down-regulated miR-200b. Interestingly, these two miRNAs inversely affected cell-cell interaction and cell motility, and they together conferred looser cell attachment and a more motile feature. miR-375 was found to be directly transactivated by ASH1. Global gene expression analysis using miR-375-introduced A549 cells and the subsequent pathway analysis using the Ingenuity IPA software revealed altered gene expressions in several cancer-related pathways (e.g., cellular movement and morphology). Interestingly, we also found that miR-375 alone can induce NE differentiation markers in A549 cells and that miR-375 is required to elicit ASH1-indued NE features. In accordance with these findings in vitro, clear induction of NE features as well as enhanced tumor growth was observed in xenografts of A549 cells stably expressing miR-375.
We further found that a transcriptional co-activator YAP1 is most significantly repressed by miR-375 through recognition of its two miR-375 binding sites. A positive correlation between ASH1 and miR-375 as well as a negative correlation between miR-375 and YAP1 were observed in lung cancers, indicating the ASH1-miR-375-YAP1 regulatory pathway is indeed functionally implemented in lung cancer cells. In addition, we found that growth-regulatory functions of YAP1 is cell-lineage dependent in lung cancer cell lines. In conclusion, the present study identified the ASH1-miR-375 axis, providing clues for a better understanding of the molecular and cellular biological roles of ASH1-centered microRNA regulatory networks in the pathogenesis of NE-lung 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 3992. doi:10.1158/1538-7445.AM2011-3992
Abstract 4006: Orphan nuclear receptor tailless TLX performs an oncogenic function in prostate cancer cells via its promotion of androgen-independent growth and induction of epithelial – mesenchymal transition phenotype
Authors: Wu Ding Lan , Cheng Cho Yiu , Chan Franky Leung 
Published: June 2012

Abstract
The Tailless TLX gene (NR2E1), which was initially identified as a vertebrate homolog to the Drosophila terminal-gap gene tailless (tll), is an orphan nuclear receptor and functions mainly as a constitutive transcriptional repressor. Functional studies show that TLX plays important roles in the maintenance and self-renewal of both embryonic and adult neural stem cells. Transgenic mice with TLX overexpression show that in vivo ectopic TLX expression can lead to uncontrolled expansion of a subgroup of neural stem cells and cause initiation of glioma. In a preliminary screening of expression patterns of nuclear receptors in prostatic cell lines and clinical prostate cancer tissues, we identified that TLX transcripts were significantly overexpressed in many prostate cancer cell lines. Furthermore, by immunohistochemistry, increased TLX nuclear immunosignals were detected in high Gleason-scored (≥4) and also hormone-refractory (castration- and flutamide- resistant) prostate cancer, paired neoplastic human prostatic tissues, suggesting that TLX up-regulation may be positively associated with the advanced progression of prostate cancer. Based on these observations, we hypothesize that TLX may play growth regulatory roles in prostate cancer development. In order to elucidate the functional significance of TLX in prostate cancer growth, we generated stable TLX-infectants in a hormone-sensitive prostate cancer line LNCaP, which expressed low endogenous TLX levels, for growth phenotypic characterization. Our results showed that ectopic TLX expression could enhance the cell proliferation of LNCaP-TLX cells in either normal growth medium or medium with charcoal-stripped fetal bovine serum, accompanied with a decreased p21 expression. The LNCaP-TLX transduced clones, which expressed decreased androgen receptor (AR) and prostatic specific antigen (PSA) expressions, were less sensitive to AR agonist R1881 and antagonist bicalutamide, suggesting that LNCaP-TLX clones were less dependent on androgen but resistant to anti-androgen. Lastly, we also found that LNCaP-TLX infectants become apparently fusiform-shaped and expressed evaluated levels of two epithelial-mesenchymal transition (EMT) markers, Twist and Vimentin, suggesting that an EMT phenotype was induced in LNCaP-TLX cells. Taken together, our results demonstrated for the first time orphan nuclear receptor TLX may play an oncogenic regulatory role in the advanced growth of prostate cancer.
(This study was supported by a Direct Grant for Research CUHK, project code 2041534)
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 4006. doi:10.1158/1538-7445.AM2011-4006