bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2185: DLEU7 is a putative tumor suppressor in glioblastoma
Authors: Efanov Alexey A. , Palamarchuk Alexey , Zanesi Nicola , Nazaryan Natalia , Croce Carlo M. , Pekarsky Yuri 
Published: June 2012

Abstract
DLEU7 was first identified as a tumor suppressor in B-CLL. We previously showed that Dleu7 functions as a potent NF-kappaB and NFAT inhibitor. To investigate possible function of Dleu7 in brain tumorigenesis we carried out the real-time PCR of RNAs isolated from different parts of human brain, brain tumors and brain tumor cell lines and found that expression of DLEU7 significantly decreased in brain tumor cell lines and brain tumors (glioblastoma) in comparison with normal brain tissues. We further investigated the effect of DLEU7 expression in HTB-15 glioblastoma cell line. Our results showed that Dleu7 overexpression resulted in apoptosis and cell cycle halt. In addition, adenovirus-mediated DLEU7 expression resulted in 100 percent increase of caspase 3/7 activation compared to AdenoGFP control in HTB-15 cells. Our data indicate that DLEU7 may play a tumor suppressor role in glioblastoma.
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 2185. doi:10.1158/1538-7445.AM2011-2185
Abstract 235: Beyond KRAS mutation status: Influence of KRAS copy number alteration and microRNAs in response to cetuximab in metastatic colorectal cancer patients
Authors: Mekenkamp Leonie J.M , Tol Jolien , Dijkstra Jeroen , De Krijger Inge , Vink-Borger M Elisa , Teerenstra Steven , Verwiel Eugene , Koopman Miriam , Meijer Gerrit A. , van Krieken J. Han J.M. , Kuiper Roland , Punt Cornelis J.A. , Nagtegaal Iris D. 
Published: June 2012

Abstract
Introduction: KRAS mutation is a negative predictive factor for treatment with anti-epidermal growth factor receptor (EGFR) antibodies in metastatic colorectal cancer (mCRC). Novel predictive markers are required to further improve the selection of patients for this treatment. We assessed the influence of modification of KRAS by gene copy number aberration (CNA) and microRNAs (miRNAs) in correlation to clinical outcome in mCRC patients treated with cetuximab in combination with chemotherapy and bevacizumab.
Patients and methods: Formalin-fixed paraffin-embedded primary tumor tissue was used of 34 mCRC patients from a phase III trial (CAIRO2), who were selected based upon their good (n=17) and poor (n=17) progression-free survival (PFS) upon treatment with cetuximab in combination with capecitabine, oxaliplatin, and bevacizumab. Gene CNA at the KRAS locus was assessed using a high resolution genome-wide array CGH and the expression levels of 17 miRNAs targeting KRAS were determined by real-time PCR.
Results: Copy number loss of the KRAS locus was observed in the tumor of 5 patients who were all good responders including patients with a KRAS mutation. Copy number gains in two wild type-KRAS tumors were associated with a poor PFS. Increased expression of several miRNAs (presented at the meeting) targeting KRAS correlated with PFS of patients treated with cetuximab, bevacizumab and chemotherapy.
Conclusion: Our results indicate that the assessment of KRAS CNA and miRNAs targeting KRAS further optimize the selection of mCRC eligible for anti-EGFR therapy, in addition to KRAS mutation status.
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 235. doi:10.1158/1538-7445.AM2011-235
Abstract 2385: Activated Kras and INK4a/Arf deficiency cooperate to produce pancreatic cancer involved with Notch and NF-κB pathways
Authors: Wang Zhiwei , Banerjee Sanjeev , Ahmad Aamir , Azmi Asfar S. , Bao Bin , Ali Shadan , Mohammad Ramzi M. , Miele Lucio , Korc Murray , Sarkar Fazlul H. 
Published: June 2012

Abstract
Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related death in the United States. Therefore, novel strategies for the prevention and treatment are urgently needed. Kras mutations are observed in 80%-90% of pancreatic cancer. Oncogenic Kras is involved with the initiation or early phase of PDAC. To understand the molecular mechanisms, several mouse models of PDAC have been generated by targeting a conditionally mutated KrasG12D to recapitulate the progression of PDAC. It was previously shown that one mouse model which activated Kras and Ink4a/Arf deficiency cooperate to produce metastatic PDAC. However, the molecular mechanism(s) by which Kras and Ink4a/Arf deficiency contribute to PDAC has not been fully elucidated. Here, we assessed the molecular alterations in mice which are activated Kras and Ink4a/Arf deficiency. For the first time, we demonstrated that deletion of Ink4a/Arf in Kras expressing mice leads to PDAC partly through Notch and NF-κB signaling pathways. Moreover, we show that several miRNAs, such as miR-200 family and miR-34 could partially play roles in tumorigenesis in activated Kras and Ink4a/Arf deficiency mice.
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 2385. doi:10.1158/1538-7445.AM2011-2385
Abstract 2457: Nestin regulates pancreatic cancer stem cell functions
Authors: Matsuda Yoko , Yamahatsu Kazuya , Kawahara Kiyoko , Suzuki Taeko , Fujii Takenori , Yamamoto Tetsushi , Korc Murray , Naito Zenya , Ishiwata Toshiyuki 
Published: June 2012

Abstract
Background: Nestin, a class VI intermediate filament protein, was originally described as a neuronal stem cell/progenitor cell marker. Nestin expression has also been shown to be up-regulated in progenitor cells in muscle, testis, teeth and pancreas. In the pancreas, lineage-tracing experiments have indicated that exocrine cells are derived from Nestin-expressing progenitor cells. Moreover, activation of K-ras in the nestin cell lineage is sufficient for the initiation of premalignant pancreatic intraepithelial neoplasia lesions in mice. To examine cancer stem cell (CSC) functions, floating cultures in plates with a low-attachment surface have been widely employed. CSCs are reported to be able to grow in floating spheres in serum-free culture medium supplemented with epidermal growth factor (EGF) and/or fibroblast growth factor-2 (FGF-2), whereas non-CSCs, more differentiated non-CSCs cannot form spheres. In this study, we examined nestin expression in spheres and clarified whether nestin regulates sphere forming activity. Methods: Human pancreatic ductal adenocarcinoma (PDAC) cell lines, PANC-1, KLM-1, MIAPaCa-2 and PK-45H were used to perform sphere-forming assay in ultra-low attachment plates supplemented with EGF and FGF-2. Expression of CSC markers including CD133, CD44, CD24, epithelial specific antigen (ESA), and nestin in spheres were determined by real time RT-PCR and immunocytochemistry. Sphere-forming cells were dispersed with trypsin, and then cell growth and migration were assessed. Next, short hairpin RNA (shRNA) targeting nestin was stably transfected into PANC-1 and PK-45H, human PDAC cells, which express high levels of nestin, in order to assess the effects of decreased nestin expression on sphere-forming ability. Conversely, KLM-1 cells which express low level of nestin were stably transfected with a nestin expression vector and their sphere forming ability was then determined. Results: All the PDAC cell lines formed spheres, and all CSC markers examined were expressed in the spheres. The sphere cells showed low cell growth rates and increased cell migration as compared to non-sphere cells. Expression levels of nestin in the spheres of PDAC cells were higher than those of non-sphere cells. Nestin shRNA transfected PANC-1 and PK-45H cells showed a marked decrease in sphere number and diameter. By contrast, nestin-gene-transfected KLM-1 cells exhibited increased sphere formation. Conclusion: Nestin is a pancreatic CSC marker that promotes the sphere-forming ability of CSCs. Therefore, nestin may represent a novel therapeutic target for CSCs in PDAC.
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 2457. doi:10.1158/1538-7445.AM2011-2457
Abstract 2500: Radiosensitizing effects of neem leaf extract in human neuroblastoma xenograft is through modulation of apoptotic pathway
Authors: Veeraraghavan Jamunarani , Aravindan Sheeja , Natarajan Mohan , Awasthi Vibhudutta , Herman Terence S. , Aravindan Natarajan 
Published: June 2012

Abstract
Induction of apoptosis is directly correlated with the biological effectiveness of radiation (IR). Recently we have shown in neuroblastoma (NB) cells that IR modulates apoptotic signaling cascade and further demonstrated that fractionation relatively impede IR-induced cell death. It is therefore important to identify bioactive compounds that enhance IR-induced cell death and potentiate the use of radiotherapy in NB patients. In this study, we investigated the efficacy of neem leaf extract (NLE) on IR-associated apoptotic transcriptional modulation and cell death. NB xenografts developed in athymic NCr-nu/nu nude mice with human SK-N-MC cells were exposed to SDR (10Gy) or FIR (2Gy/Day for 5days) with or without NLE. IR exposures were limited to the tumor in flank region, while rest of the animal was protected by a specially designed cerrobend shield. Transcriptional activation of 84 apoptotic pathway focused genes was assessed using QPCR profiling. Cell death was measured using TdT nick end labeling. The results revealed that FIR significantly induced 55 genes and suppressed 10 genes, while SDR induced 49 and suppressed 5 genes. Of these, 46 genes were upregulated and 4 genes were downregulated after FIR and SDR, respectively. NLE inhibited 14 FIR-induced and 15 SDR-induced genes in human NB xenograft. To that end, NLE significantly inhibits anti-apoptotic NAIP, Birc6, Birc8, NOL3 after both SDR and FIR. Conversely, NLE significantly enhanced FIR- and SDR-induced pro-apoptotic BAK1, BAX, BCL10, Casp1, Casp10 CARD8 and CRADD in this setting. Furthermore, compared to mock-IR, DNA fragmentation analysis revealed that FIR and SDR significantly increased cell death. More importantly, NLE robustly and significantly conferred FIR- and SDR-induced cell death. Together, these data imply that NLE may exert radiosensitization mutually by activating pro-apoptotic signaling and negating survival signaling and, may thus serve as a potential “deliverable” to further potentiate radiotherapy in mitigating NB progression and relapse.
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 2500. doi:10.1158/1538-7445.AM2011-2500
Abstract 2585: Snail-p53 interaction inhibitor GN25 and its combination with Oxaliplatin targets both hedgehog signaling and K-ras pathway in pancreatic cancer
Authors: Azmi Asfar S. , Park Bum-Joon , Mohammad Ramzi M. 
Published: June 2012

Abstract
Activation of hedgehog (Hh) signaling is widely observed in human cancers including pancreatic cancer (PC). Similarly, mutations in K-Ras gene is found in &gt;80% of PC. Constitutive activation of Hh signaling component Gli in turn enhances p53 suppressor Snail. Studies from our group have revealed that p53 is further suppressed by direct binding with oncogenic K-Ras-induced Snail. Therefore in order to target combined suppressive effects of Hh signaling and K-Ras-induced snail on p53 pathway, a specific inhibitor of the p53-Snail binding (GN25) was developed. This inhibitor can induce p53 expression and functions in K-Ras-mutated cells, with no toxicity to normal cells (Oncogene 2010). Here we show that GN25 when combined with Oxaliplatin induces synergistically (combination index CI&lt;1) enhanced growth inhibition (MTT) and apoptosis (Histone DNA ELISA and Annexin V FITC) in multiple PC cell lines (AsPC-1, Capan-2, BxPC-3 and Colo-357) irrespective of the mutational or functional status of both p53 and K-Ras. Interestingly, we found that some of the above cell lines have hyper activation of Hh signaling that results in constitutively over activation of Gli. Western blot analysis demonstrated that GN25/oxaliplatin re-activated the p53 protein and downstream effector molecules such as pro-apoptotic Bax and cell cycle regulator p21. Further analysis showed that GN25/oxalipltin interferes with the Hh signaling and suppresses Snail. In SCID mice studies in vivo, the maximum tolerated dose of GN25 was found to be 35 mg/kg i.v. In addition, it can be given in combination with oxaliplatin at 5 mg/kg i.p twice a week for two weeks. The combination studies of GN25/oxaliplatin in multiple tumor xenografts (wt-k-Ras BxPC-3 and AsPC-1 mut-p53 k-Ras) are ongoing. So far our results suggest that GN25/oxaliplatin is a strong combination against hyper activated Hh and mutant K-Ras-initiated human pancreatic cancer irrespective of mutational status of p53.
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 2585. doi:10.1158/1538-7445.AM2011-2585
Abstract 2596: Identification and characteration of IKBKE kinase inhibitor selectively inhibits tumor growth in cancer cells
Authors: Guo Jianping , Kim Donghwa , Cheng Jin Q. 
Published: June 2012

Abstract
The serine/threonine kinase IKBKE is frequently altered in human cancer. Ectopic expression of IKBKE induces malignant transformation, cell migration, invasion and chemoresistance. Thus, IKBKE is an attractive target for anti-cancer drug discovery. By screening a small molecule compound library, we identified an IKBKE inhibitor, MCCK1. It inhibits IKBKE kinase as well as downstream targets of IKBKE including phosphorylation such as Iκ-Bα, P65 and IRF3. MCCK1 is highly selective for IKBKE and does not inhibit the activation of IKKβ, STAT3, Erk-1/2, p38 or JNK. The inhibition of IKBKE by MCCK1 results in induction of cell growth arrest and apoptosis selectively in human cancer cells that harbor aberrant expression IKBKE. Further, MCCK1 inhibits tumor growth in nude mice of human cancer cells in which IKBKE is elevated but not of those cancer cells in which it is not. These data indicate that MCCK1 is an IKBKE inhibitor with anti-tumor activity in vitro and in vivo and could be a potential anti-cancer agent for patients whose tumors express elevated IKBKE.
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 2596. doi:10.1158/1538-7445.AM2011-2596
Abstract 26: Gene expression profiling of oral cancer cells chronic exposed to areca nut extract
Authors: Li Yi-Chen , Cheng Ann-Joy 
Published: June 2012

Abstract
Oral cancer is the 6th most frequent cancer in Taiwan. The habit of areca nut chewing is the main etiological factor of oral cancer. To shed light on molecular basis of areca nut associated oral carcinogenesis, we established two oral cell sublines chronically treated with areca nut extract (ANE) at IC70 dose for 2 months. Affymatrix microarray was used in transcriptome profiling between parental and ANE sublines of oral cancer cells. Algorithmic analysis was applied to analyze the network regulatory pathways. RT-PCR was used to validate the genes altered expressions in ANE-sublines. Total of 35 genes was differentially expressed in both sublines. Several functional pathways were apparently altered, with lipid metabolism (P=1.95×10−10), oxidative phosphorylation (P=1.02×10−6), and cell adhesion (P=9.66×10−6) most significant. Seven genes were confirmed over 2-fold of changes, including HMGCS1, KRT-17 up-regulation and SMC4, CENPF, ID-1, IL1-alpha and Ches1 down-regulation. Further study revealed Ches1 was down regulation upon arecoline treatment. Consistently, this gene was reduced expression in 52% of oral cancer tissues, which was significantly correlated with areca nut chewing habit of patients (p = 0.04). Thus, these results provide information regarding the molecular mechanisms of areca nut-induced oral carcinogenesis.
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 26. doi:10.1158/1538-7445.AM2011-26
Abstract 2627: Antitumor effect in human lung cancer by a combination treatment of novel histone deacetylase inhibitors: SL142 or SL325 and retinoic acids
Authors: Fukazawa Takuya , Han Shaoteng , Yamatsuji Tomoki , Mastuoka Junji , Miyachi Hiroyuki , Morita Ichiro , Takaoka Munenori , Maeda Yutaka , Naomoto Yoshio 
Published: June 2012

Abstract
Histone deacetylase (HDAC) inhibitors arrest cancer cell growth and cause apoptosis with low toxicity thereby constituting a promising treatment for cancer. In this study, we investigated the anti-tumor activity in lung cancer cells of the novel cyclic amide-bearing hydroxamic acid based HDAC inhibitors SL142 and SL325. In A549 and H441 lung cancer cells both SL142 and SL325 induced more cell growth inhibition and cell death than the hydroxamic acid-based HDAC inhibitor suberoylanilide hydroxamic acid (SAHA). Moreover, the combination treatment using retinoid drugs ATRA or 9-cis RA along with SL142 or SL325 significantly induced more apoptosis and suppressed colony formation than the single use of either. The expression of the retinoic acid receptors RAR α, RAR β, RXR α and RXR β were unchanged with the treatment. However a luciferase reporter construct (pGL4. RARE 7x) containing seven tandem repeats of the retinoic acid responsible element (RARE) generated significant transcriptional activity after the combination treatment of retinoic acids and SL142 or SL325 in H441 lung cancer cells. Moreover, apoptosis-promoting Bax expression and caspase-3 activity was increased after the combination treatment. These results suggest that the combination treatment of SL142 or SL325 with retinoic acids exerts significant anti-tumor activity and is a promising therapeutic candidate to treat human lung cancer.
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 2627. doi:10.1158/1538-7445.AM2011-2627
Abstract 2629: Sustained immediate-early gene induction is linked to histone deacetylase inhibitor-induced apoptosis in multiple tumour types
Authors: Chueh Anderly C. , Togel Lars , Mariadason John M. 
Published: June 2012

Abstract
Introduction: Histone deacetylase inhibitors (HDACi) are a novel class of cancer therapeutics, currently approved for the treatment of cutaneous T-cell lymphoma (CTCL) and undergoing clinical trials for other haematological and solid tumours. Through screening of a panel of 30 colorectal cancer cell (CRC) lines, we previously established that HDACi-induced apoptosis is linked to a specific transcriptional response consisting of induction of multiple immediate-early (IE) and stress response genes. The purpose of this study was to investigate whether the findings made in colorectal cancer cells are applicable to other tumor types and to further elucidate the mechanism of apoptosis induction involving IE genes.
Results: We screened a panel of 40 tumor cell lines including that of CTCL, multiple myeloma, NSCLC, melanoma, breast and prostate cancer, for HDACi (sodium butyrate and Vorinostat) sensitivity by PI/FACS analysis and identified highly sensitive and resistant cell lines. Consistent with the findings made in CRCs, quantitative RT-PCR analysis revealed that the expression of six representative IE genes (Fos, Jun, Atf3, Egr1, Egr3, Gadd45b) were preferentially induced by HDACi treatment in the 5 most sensitive cell lines compared to the 5 most refractory tumor cell lines. To study kinetics of IE gene induction, we performed time-course experiments on cancer cell lines treated with various stimuli, including EGF, phorbol ester PMA, and HDACi. While EGF and PMA induce IE gene expression in a rapid and transient manner, HDACi-induction of IE gene expression is sustained over 24 hours, suggesting that the prolonged expression of these genes may be responsible for apoptosis induction. By transient transfection of siRNA into tumour cell lines, we demonstrated that the down-regulation of the IE genes Jun and Atf3 partially blocks HDACi-induced apoptosis.
Conclusions: We demonstrated that HDACi-induced apoptosis is linked to sustained transcriptional induction of multiple IE genes in a variety of cancer cells. Furthermore, we demonstrated that IE genes of the AP-1 transcription factor family Jun and Atf3 are directly involved in the apoptosis response induced upon HDACi treatment.
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 2629. doi:10.1158/1538-7445.AM2011-2629