bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 190: Long noncoding RNA XY11-10-11 regulates proliferation and migration of esophageal adenocarcinoma cells
Authors: Yang Xue , Wu Wenjing , Margolies Nathaniel , Song Jee Hoon , Cheng Yulan , Meltzer Stephen J. 
Published: August 2012

Abstract
Esophageal carcinoma is one of the most common types of cancer, ranked among the top eight causes of cancer death worldwide. The molecular mechanisms underlying esophageal cancer are very complicated and have not yet been completely clarified. In recent years, long noncoding RNAs (lncRNAs) have been shown to play critical regulatory roles in various cancer biology, yet their potential involvement in esophageal cancer is not well understood. Here, we identified a set of lncRNAs that are differentially expressed in esophageal cancer tissues in comparison to the normal tissues using quantitative real-time polymerase chain reaction. A new lncRNA, which we name XY11-10-11, is significanty increased in expression in human esophageal adenocarcinoma tissues and cell lines. XY11-10-11 is an intergenic lncRNA expressed from a locus located on chromosome 14. Importantly, knockdown of XY11-10-11 by siRNA resulted in inhibition of proliferation and migration in esophageal adenocarcinoma cells (EACs). Moreover, patients with high XY11-10-11 expression levels had a relatively poorer prognosis. Our findings indicate that XY11-10-11 may play a significant role in the development or progression of esophageal adenocarcinoma and may be an potential biomarker for diagnosis and therapy.
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 190. doi:1538-7445.AM2012-190
Abstract 1901: EGFR and K-Ras mutations and resistance of lung cancers to IGF-1R TKI
Authors: Kim Woo-Young , Prudkin Ludmila , Feng Lei , Kim Edward , Hennessy Bryan , Lee Ju-Seog , Lee J. Jack , Glisson Bonnie , Lippman Scott , Wistuba Ignacio , Hong Waun Ki , Lee Ho-Young 
Published: August 2012

Abstract
Background: Most patients with non-small cell lung cancer (NSCLC) have responded poorly to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). We investigated the involvement of insulin-like growth factor 1 receptor (IGF-1R) signaling in primary resistance to EGFR TKIs and the molecular determinants of resistance to IGF-1R TKIs. Methods: Phosphorylated IGF-1R/insulin receptor (pIGF-1R/IR) was immunohistochemically evaluated in a NSCLC tissue microarray. We analyzed the antitumor effects of an IGF-1R TKI (PQIP or OSI-906), either alone or in combination with a small-molecular inhibitor (PD98059 or U0126) or with siRNA targeting K-Ras or MAPK/extracellular signal-regulated kinase kinase (MEK), in vitro and in vivo in NSCLC cells with variable histologic features and EGFR or K-Ras mutations. Results: pIGF-1R/IR expression in NSCLC specimens was associated with a history of tobacco smoking, squamous cell carcinoma histology, mutant (mut) K-Ras, and wild-type (wt) EGFR, all of which have been strongly associated with poor response to EGFR TKIs. IGF-1R TKIs exhibited significant antitumor activity in NSCLC cells with wt EGFR and wt K-Ras but not in those with mutations in these genes. Introduction of mut K-Ras attenuated the effects of IGF-1R TKIs on NSCLC cells expressing wt K-Ras. Conversely, inactivation of MEK restored sensitivity to IGF-TKIs in cells carrying mut K-Ras. Conclusions: The mutation status of both EGFR and K-Ras could be predictive markers of response to IGF-1R TKIs. Also, MEK antagonism can abrogate primary resistance of NSCLC cells to IGF-1R TKIs.
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 1901. doi:1538-7445.AM2012-1901
Abstract 1906: Mechanisms of resistance to EGFR tyrosine kinase inhibitors involving HER-family ligands and receptors
Authors: Iwanaga Kentaro , Sueoka-Aragane Naoko , Sato Akemi , Nakamura Tomomi , Kobayashi Naomi , Sueoka Eisaburo , Kimura Shinya 
Published: August 2012

Abstract
Known mechanisms of acquired resistance to EGFR tyrosine kinase inhibitor (EGFR-TKI), including the second mutation of EGFR, T790M, MET amplification, and HGF overexpression, explain approximately 60% of cases, but the remaining mechanisms have not been clarified. To investigate novel mechanisms of acquired resistance to EGFR-TKI, we examined HER-family ligands and HER-family receptor status in non-small cell lung carcinoma (NSCLC) cell lines (n=13). Cell lines were divided into two groups with respect to EGFR-TKI sensitivity: highly sensitive (HCC827, PC-9, HCC2935, and HCC4006) and resistant (H1395, H1666, H596, H1437, A549, H226B, H1299, H460, H1792). We examined expression levels of eleven HER-family ligands_EGF, TGFβ, amphiregulin (AREG), betacellulin (BTC), HB-EGF, epigen (EPGN), epiregulin (EREG), and neuregulin (NRG) 1, NRG2, NRG3, and NRG4_in these cell lines. NRG2, NRG4, and EPGN were expressed at 39.5-, 31.4-, and 6.5-fold higher levels, respectively, in EGFR-TKI primary resistant NSCLC cell lines than in highly sensitive cell lines, whereas TGFA, EGF, and AREG were expressed at 0.22-, 0.3-, and 0.34-fold lower levels. Phosphorylation of EGFR was elevated in sensitive cell lines compared to resistant cell lines, but HER2-4 receptors did not evidence a difference in phsophorylation. These results suggest that the EGFR pathway is activated in sensitive cell lines, and HER2-4, which binds to EPGN, EREG, NRG2, and NRG4, might be activated in resistant cell lines. We prepared cell lines HCC827GR and HCC827ER, derived from HCC827, which acquired resistance to gefitinib or erlotinib, respectively. We analyzed HER-family ligands and receptors using these cell lines. Compared to parent cells, EPGN, EREG, HB-EGF, TGFA, NRG1, and AREG were up-regulated in HCC827GR. Phosphorylation status of EGFR, HER2, and HER3 was not altered, but that of HER4 was increased in HCC827GR. In HCC827ER, EGFR binding ligands AREG, BTC, and EGF were down-regulated, while phosphorylation of EGFR, HER2, and HRE3 was decreased. However, NRG2 was remarkably elevated and HER4 and its downstream STAT5 were phosphorylated. These results indicate that HER4 and its binding ligands may contribute to acquired resistance to EGFR-TKI. Considering these results, it is possible that the HER4-STAT5 pathway might be common to primary and acquired resistance to EGFR-TKI. We continue to investigate its significance.
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 1906. doi:1538-7445.AM2012-1906
Abstract 1923: The mTOR kinase inhibitor, CC214, preferentially blocks the growth of EGFRvIII-activated glioblastomas
Authors: Gini Beatrice , Guo Deliang , Nathanson David , Shackelford David , Zhu Shaojun , Yang Huijun , Tanaka Kazuhiro , Babic Ivan , Akhavan David , Bonetti Bruno , Mortensen Deborah , Xu Shuichan , Raymon Heather , Chopra Rajesh , Mischel Paul 
Published: August 2012

Abstract
mTOR pathway hyper activation is a common feature in many cancers, including in nearly 90% of Glioblastomas. mTOR exists in two multiprotein complexes, which differ in regulation, function, and response to the allosteric mTOR inhibitor rapamycin. The failure of glioblastomas to clinically respond to rapamycin appears to be mediated both by inability of rapamycin to inhibit mTORC2 signaling, and by failure to fully suppress p4E-BP1, a critical effector of mTORC1. The new generation of mTOR kinase inhibitors (mTORki) has emerged as a new class of targeted cancer therapies capable of blocking mTOR more potently than rapalogs (such as Rapamycin). Here we demonstrate that CC214-1 and CC214-2, mTOR kinase inhibitors, have potent effects on the growth of glioblastoma in vitro and in vivo. Across a panel of GBM cell lines, CC214-1 was significantly more effective at suppressing 4E-BP1 phosphorylation and protein translation, and mTORC2 signaling than rapamycin, resulting in significantly more growth inhibition at equal levels of suppression of S6 phosphorylation. EGFRvIII, the constitutively active EGFR mutant frequently detected in GBMs strongly activates mTORC1 and mTORC2 signaling, potently sensitizing tumors to CC214-1. In contrast, PTEN expression suppressed mTOR signaling and reduced the response to CC214-1. In vivo CC214-2 significantly inhibited mTORC1 and mTORC2 signaling, significantly suppressing tumor growth by 50%. CC214-1 also potently activated autophagy. Addition of chloroquine suppressed autophagy resulting in significant CC214-1-dependent apoptotic cell death. These results demonstrate the potential activity of mTOR kinase inhibitors in GBM, and identify EGFRvIII expression and PTEN loss as molecular determinants of response. These data also suggest that mTOR kinase inhibitors, alone or in combination with autophagy inhibiting agents, are likely to have significant anti-tumor efficacy in GBM patients.
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 1923. doi:1538-7445.AM2012-1923
Abstract 1924: The aurora kinase inhibitor CYC3 synergizes with low concentrations of paclitaxel in pancreatic cancer cells in vitro
Authors: Lin Yao , Krippendorff Ben-Fillippo , Bramhall Jo , Bapiro Tashinga , Richards Frances , Jodrell Duncan , Zheleva Daniella 
Published: August 2012

Abstract
CYC3, an Aurora Kinase A specific inhibitor, suppresses the pancreatic cancer cell growth (72h GI50 2.4μM in MiaPaCa-2 cells and 1.95μM in Panc-1 cells), arrest the cells at M phase and induces apoptosis. In order to evaluate CYC3's clinical potential, we employed mathematical models and simulations to look for possible synergistic combinations of CYC3 with paclitaxel in MiaPaCa-2 and Panc-1 cells. We have identified low concentrations of paclitaxel (3nM) and CYC3 is synergistic in inhibiting pancreatic cell growth, achieving similar effects as high concentrations of paclitaxel (30nM). Liquid Chromatography-Mass Spectrometry (LC-MS) analysis shows that CYC3 does not alter the cellular uptake of paclitaxel, supporting a synergistic mechanism at molecular level. In addition, the combination of CYC3 with low concentration of paclitaxel (3nM) displays less myelotoxicity compared to high concentrations of paclitaxel (30nM) in colony formation assay using Colony Forming Unit of Granulocyte and Macrophage (CFU-GM) (60-70% vs 100% inhibition), suggesting a potentially safer but equally efficient application of paclitaxel in patients.
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 1924. doi:1538-7445.AM2012-1924
Abstract 1927: Mechanistic characterization of SC144 in colon cancer
Authors: Xu Shili , Oshima Takashi , Grande Fedora , Neamati Nouri , Garofalo Antonio 
Published: August 2012

Abstract
Recently, we have designed and synthesized a novel quinoxalinhydrazide, SC144, that showed cytotoxicity in a panel of human cancer cell lines. Here, we found that SC144 exhibited anticancer activity in a panel of drug-sensitive and drug-resistant colon cancer cell lines. To study the molecular anticancer mechanism of SC144, we further found that it arrested cell cycle progression and induced apoptosis in colon cancer cells, which is associated with the decrease in cyclin D1 expression and the activation of the p38/IL-24/Fas pathway. Additionally, in surgical specimens from 202 colorectal patients, Cyclin D1 expression was significantly higher and IL-24 expression was significantly lower in cancer tissue than in adjacent normal mucosa, and there was a significant correlation between IL-24 level in colorectal cancer tissue and the survival rate of patients after cytoreductive surgery (P = 0.007). This clinical evidence further supports that SC144 is a promising therapeutic agent for colon cancer therapy.
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 1927. doi:1538-7445.AM2012-1927
Abstract 193: Prognostic impact of miR-146 polymorphism in patients with resected colorectal cancer
Authors: Kang Byung Woog , Lee Soo Jung , Moon Joon Ho , Chae Yee Soo , Sohn Sang Kyun , Kim Jong Gwang 
Published: August 2012

Abstract
Background: MicroRNAs (miRNAs) are small noncoding RNAs with regulatory functions as tumor suppressors and oncogenes. The rs2910164 is a C to G polymorphism located within the sequence of miR-164a precursor, which leads to a change from a C:U pair to a G:U mismatch in its stem region. Recent evidence suggested that the rs2910164 SNP in miR-146a was associated with development of familial breast and ovarian cancers, and prostatic cancer. The aim of this study was to investigate the association between this genetic variant and prognosis of colorectal cancer (CRC) operated curatively. Methods: A total of 343 CRC patients underwent curative surgery were consecutively enrolled between 2004 and 2006. DNA was extracted from fresh frozen normal tissue and miR-146 polymorphism was genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: With a median follow up of 42.3 months, the combined GG+CG genotype demonstrated a better survival outcome compared with the CC genotype in a Kaplan-Meier survival analysis. Multivariate analysis showed that the G allele of miR-146 was associated with better progression-free and disease-specific survival as a dominant model adjusted to age, sex, histologic grade and stage [HR=0.54 and 0.49; P = 0.018 and 0.025, respectively]. Moreover, the tumors containing the G allele were histologically associated with more prominent lymphovascular invasion. Conclusions: Our results suggest that miR-146 polymorphism is possible prognostic marker in operated CRC patients in Korean.
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 193. doi:1538-7445.AM2012-193
Abstract 1930: Inhibition of glioblastoma cell growth with the isoprenoids perillyl alcohol, farnesol, and geraniol
Authors: Dickerson Lindsy , Jain Aditi , Crowell Pamela L. , Lai James C. K. , Bhushan Alok 
Published: August 2012

Abstract
The naturally occurring isoprenoid perillyl alcohol has chemotherapeutic activity toward many solid tumor types. Early phase human clinical trials have shown low toxicity but only limited efficacy. In glioblastoma, perillyl alcohol has antitumor activity toward cultured cells and has shown some survival benefit in a Phase I/II clinical trial. More potent compounds are needed in order to make more significant impacts on patient survival from glioblastoma and other chemoresistant cancers. Isoprenoids may be especially useful in glioblastoma given their lipophilic nature and potential to cross the blood-brain barrier. Here, we compared the chemotherapeutic effects of perillyl alcohol with the related isoprenoids farnesol and geraniol on cell survival in cultured U87 human glioblastoma cells. Cells were treated for 72 h with isoprenoids, and cell survival was measured by the MTT assay. In U87 cells, each of the isoprenoids exhibited a dose-dependent effect on cell survival in the range of 0-2 mM. The relative potency was farnesol&gt;perillyl alcohol&gt;geraniol, with 52%, 38% and 23% inhibition at 1500 uM, respectively. We then tested the effects of isoprenoids on mitogenic signaling via ERK, phosphoERK, AKT and phosphAKT Western blots in U87 cells. Farnesol decreased phosphoERK at doses as low as 50 uM, whereas perillyl alcohol and geraniol had no effect. None of the isoprenoids affected phosphoAKT, total AKT, or total ERK. Together, these data suggest that farnesol may be a more effective agent than perillyl alcohol in the chemotherapy of glioblastoma, and its effects may be due in part to inhibition of ERK phosphorylation.
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 1930. doi:1538-7445.AM2012-1930
Abstract 1935: Potent anti-tumor effects of TIC10 require Foxo3a and TRAIL gene upregulation
Authors: Allen Joshua E. , Krigsfeld Gabriel , Patel Akshal S. , Wu Gen Sheng , Dicker David T. , El-Deiry Wafik S. 
Published: August 2012

Abstract
TNF-related apoptosis-inducing ligand (TRAIL; Apo2L) is an endogenous protein that induces tumor-selective apoptosis and is currently being tested in clinical trials as an anti-tumor agent. Despite promising preclinical activity, recombinant human TRAIL suffers from efficacy-limiting properties such as short serum half-life, stability, cost, and limitations in delivery, e.g. to the central nervous system. We hypothesized that induction of the human TRAIL gene by small molecules may overcome these limitations of TRAIL-based protein therapy. A cell-based luciferase reporter screen using the human TRAIL promoter identified TIC10 as a p53-independent small molecule inducer of the TRAIL gene. TIC10 induces TRAIL on the surface of normal and tumor cells, in sera of non-tumor-bearing mice, and throughout the tumor microenvironment. Co-culture experiments suggest that TRAIL upregulation by normal cells can contribute to the anti-tumor response of TIC10 through a TRAIL-mediated bystander effect. TIC10-induced TRAIL causes tumor-specific and TRAIL-mediated cell death as indicated by inhibition of cytotoxic effects following TRAIL gene knockdown in vitro and in vivo. Expression profiling of TIC10-induced transcriptional changes revealed altered expression levels of Foxo3a target genes, including DR5. We found that TIC10 causes the nuclear translocation of Foxo3a, but not Foxo1, to upregulate TRAIL gene transcription as determined by chromatin-immunoprecipitation assays. Western blot analysis indicated that TIC10 potently inhibits the phosphorylation of Foxo3a at Ser253 and Ser294 that normally docks the transcription factor to 14-3-3 proteins in the cytosol. Dual inhibition of Akt and ERK by TIC10, by other individual small molecule kinase inhibitors in combination or targeted siRNA inhibited the phosphorylation of these critical serine residues and synergistically induced Foxo3a-dependent TRAIL and TRAIL-mediated cell death. TIC10 is a promising first-in-class anti-tumor agent with a broad range of anti-tumor effects in preclinical animal models including othrotopic GBM, immunocompetent lymphoma, xenografted colon, lung, or breast cancers, and exhibits synergy with taxanes as well as bevacizumab among other agents. TIC10 appears to have no measurable toxic effects in mice including evaluation of serum chemistries, liver function studies, LDH, tissue histology, weight of the animals or behavioral changes. We are pursuing the clinical translation of these important findings that indicate a favorable and wide therapeutic index for a novel anti-tumor agent.
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 1935. doi:1538-7445.AM2012-1935
Abstract 1973: Falcarindiol induces colorectal cancer cell death through activation of ER stress
Authors: Jin Hongri 
Published: August 2012

Abstract
Colorectal cancer is the third leading cause of cancer-related deaths in the United States. Current treatment of this cancer generally employs surgical resection combined with chemotherapy using cytotoxic drugs and radiation therapy. Because this therapy is only moderately successful for late stage cancers, novel approaches to the treatment of colorectal cancer are required. Falcarindiol is a natural polyyne from medicinal plant Oplopanax horridus that has been widely used by indigenous people for a variety of diseases. We show that Falcarindiol can selectively kill colon cancer cells but not the normal colon cells. We further show that the observed cell death is mediated through the induction of Endoplasmic Reticulum (ER) stress. We further show that inhibition of ER stress significantly block Falcarindiol-induced colon cancer cell death while knockdown of GRP78, which sensitizes cells to ER stress induced cell death, significantly enhances Falcarindiol-induced cell killing. Interestingly, we find that Falcarindiol exhibits synergistic anticancer activity with 5-FU, a chemotherapeutic drug for colon cancer. These results suggest that Falcarindiol is potentially a valuable candidate that can be used to in the treatment of colon cancer either alone or in combination with current anti-colon cancer agent such as 5-FU. Key words: Falcarindiol; Colon cancer; ER Stress; Cell death.
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 1973. doi:1538-7445.AM2012-1973
Abstract 1974: Growth inhibition and antitumor activity of chikusetsusaponin IVa methyl ester, an oleanane-type triterpenoid from the root of Acyranthes japonica, in HCT 116 human colon cancer cells
Authors: Chung Hwa Jin , Cho Lan , Park Hyen Joo , Kim Gi Dae , Son Kyun Ho , Pyee Yuna , Song Jayoung , Kim Yeong Shik , Lee Sang Kook 
Published: August 2012

Abstract
Chikusetsusaponin IVa methyl ester (CSME) is an oleanane-type triterpenoid isolated from the root of Acyranthes japonica (Amaranthaceae). In the present study, the growth inhibition and antitumor activity of CSME were investigated in cultured human colon cancer cell HCT 116. CSME inhibited the proliferation of cancer cells with an IC50 value of 22.4 μM. Flow cytometric analysis indicated that CSME markedly induced the accumulation of cells in the G0/G1 phase and the increase of cell population in sub-G1 phase. G0/G1 cell cycle arrest by CSME was associated with the down-regulation of the expression of cyclin D1, cyclin A, CDK4, CDK2, c-myc and Rb phosphorylation. The increase of sub-G1 peak by CSME was closely correlated with the induction of apoptosis, which was evidenced by the induction of cleaved poly-(ADP ribose) polymerase, activation of caspases, and suppression of Bid and Bcl-2 expression. Treatment of CSME (0.25, 1.0, or 3.0 mg/kg, i.p) also effectively suppressed tumor growth in the HCT 116 implanted xenograft nude mouse model without any overt toxicity. Taken together, these findings suggest that CSME might be a potential candidate for the development of cancer chemotherapeutic agents derived from natural products. (Acknowledgement; this study was supported by a grant Studies on the Identification of the Efficacy of Biologically Active Components from Oriental Herbal Medicines from the Korea Food and Drug Administration (2010)).
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 1974. doi:1538-7445.AM2012-1974