bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2277: Autophagy-associated necroptosis contributes to cancer cell cytotoxicity induced by the chalcone compound SBC2
Authors: He Weiyang , Wang Qiong , Srinivasan Balasubramanian , Xu Xiuling , Chen Wenshu , Padilla Mabel T. , Gou Xin , Xing Chengguo , Lin Yong 
Published: August 2012

Abstract
Chalcone-based compounds are potential agents for cancer chemoprevention and chemotherapy. The recently developed chalcone-based compound SBC2 suppresses xenograft tumor growth in nude mice, however, the mechanisms by which SBC2 kills cancer cells are elusive. In this study, we have investigated the cellular signaling pathways involved in SBC2's cytotoxicity in cancer cells derived from lung and bladder tumors. SBC2 potently killed different cancer cells, which was effectively blocked by the necroptosis inhibitor Necrostatin-1 and knockdown of the necroptosis pathway components RIP1 and RIP3, suggesting that SBC2-induced cytotoxicity is associated with necroptosis. SBC2 robustly activated JNK and ERK through activation of their upstream activating kinases MEKK1 and MKK7. Blocking JNK and ERK effectively blocked SBC2-induced cytotoxicity, implying an important role of these MAPKs in SBC2-induced cancer cell death. In addition, SBC2 strongly induced autophagy, which was suppressed when JNK was blocked. Furthermore, SBC2 triggered BCL-XL phosphorylation that was dependent on JNK. Importantly, suppression of autophagy with either pharmacological inhibitors or a siRNA targeting the essential autophagy component ATG7 effectively attenuated SBC2-induced cell death. These results suggest that SBC2 kills cancer cells through activating JNK-mediated and autophagy-associated necroptosis. Taken together, our observations substantiate SBC2 as a potential anticancer therapeutic and identify a novel pathway for cancer cell killing by SBC2 that involves autophagy and necroptosis.
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 2277. doi:1538-7445.AM2012-2277
Abstract 2295: miR-342 modulates ID4 expression in breast cancer
Authors: Crippa Elisabetta , Lusa Lara , Fiorino Antonio , Marchesi Edoardo , Cecco Loris De , Pierotti Marco A. , Gariboldi Manuela 
Published: August 2012

Abstract
Integration of the results from a transcriptome profiling of coding and non coding RNAs (miRNA) on familial (BRCA1- or BRCA2-mutated, or BRCAX) and sporadic breast cancers identified possible miRNA-dependent mechanisms associated with the different BRCA groups analyzed. Among the miRNA/target gene pairs found, we focused on that composed by miR-342 and ID4 gene. ID4 is a negative regulator of B-HLH transcription factors frequently expressed in cancer and miR-342 is deregulated in many cancers, including breast. All of our groups had relatively high expression of miR-342 and low expression of ID4, except for one subgroup of BRCAX cases (named BRCAXa, comprising cases with clinical characteristics similar to BRCA1) that had reciprocal expression patterns of this pair. We evaluated the expression levels of the putative pair in different breast cancer cell lines and found that ID4 gene expression was on average higher in estrogen receptor negative (ER-) cells; on the contrary, miR-342 had higher expression in estrogen receptor positive (ER+) cells. The direct binding of miR-342 to the 3′ UTR of ID4 and its potential inhibitory effect was functionally validated using a reporter luciferase system. Reciprocal expression of miR-342 and ID4 was then confirmed in vitro in the triple negative MDA-MB-231 cell line, that, similarly to the BRCAXa subgroup, had low expression of miR-342 and where miR-342 introduction reduced ID4 protein levels. ID4 is a negative regulator of BRCA1 and modulation of its expression in breast cancer is inversely related with that of BRCA1. Being ID4 a target of miR-342, we hypothesized a relationship between these two genes and the miRNA and that low levels of miR-342 could provide a mechanism for increasing ID4 that negatively regulates BRCA1 expression. Analysis of their levels in our cases supported this thesis. In the BRCAXa class lower levels of miR-342 were associated with reduced expression of BRCA1. We hypothesized that down-regulation of ID4 through miR-342 could provide a mechanism for increasing BRCA1 expression. We tested this hypothesis in the MDA-MB-231 cells, where we found miR-342 mediated downregulation of ID4, but no increase in the expression of BRCA1 at either gene or protein levels. These results showed that ID4 is a validated target of miR342 and propose a role of miR-342 in familial breast cancer where it could impair expression of ID4. Targets of ID4 different than BRCA1 can be altered in the BRCAXa subgroup.
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 2295. doi:1538-7445.AM2012-2295
Abstract 2309: Down-regulation of miR-181b contributes to the poor prognosis of adverse cytogenetically abnormal acute myeloid leukemia by targeting PBX3
Authors: Li Zejuan , Huang Hao , Li Yuanyuan , Jiang Xi , Chen Ping , Arnovitz Stephen , He Chunjiang , Zhang Zhiyu , Neilly Mary Beth , Price Colles , Zhang Yanming , Larson Richard , Beau Michelle Le , Rowley Janet , Chen Jianjun 
Published: August 2012

Abstract
Altered expression of microRNAs (miRNAs, a class of small regulatory RNAs) is associated with various types of cancers, including acute myeloid leukemia (AML). In our previous bead-based miRNA expression profiling assay, we observed that miR-181a, b, c, and d were all expressed at a higher level in the favorable prognosis subtypes of cytogenetically abnormal AML (CA-AML) carrying t(8;21), inv(16), or t(15;17) than in an intermediate- to poor-risk subtype of CA-AML harboring MLL rearrangements. Indeed, we found that increased expression of miR-181a or miR-181b was significantly (P&lt;0.05) associated with longer OS in univariable testing, whereas only that of miR-181b remained significant (P&lt;0.05) upon multivariable testing, after adjusting for other clinical, cytogenetic, and molecular variables. Through correlating expression of miR-181b with those of miR-181 putative target genes in 35 CA-AML patient samples, we identified 159 genes that exhibited a significantly inverse (P&lt;0.05; Pearson Correlation) correlation of expression with miR-181b. PBX3 has the most significant inverse correlation with the expression of miR-181b, so we chose PBX3 as an important candidate target of miR-181 for further studies. We conducted luciferase reporter and mutagenesis assays and showed that PBX3 is a direct target of miR-181a/b. We also showed that forced expression of miR-181a/b significantly down-regulated endogenous expression of PBX3 in MLL-rearranged leukemic cells at both the RNA and protein levels. Ectopic expression of miR-181b significantly (P&lt;.05) promoted apoptosis and decreased viability of MONOMAC-6/t(9;11), THP-1/t(9;11), and KOCL-48/t(4;11), and delayed leukemogenesis in MLL-fusion-mediated mouse leukemia model; such effects could be reversed by forced expression of PBX3 coding region. Our data suggest that the silencing of miR-181b and thereby the activation of the target genes, such as PBX3, likely contributes to the poor prognosis of adverse CA-AML patients. Thus, restoring expression of miR-181b and/or targeting the PBX3 pathways in poor prognosis AML patients may provide new strategies to improve outcome substantially.
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 2309. doi:1538-7445.AM2012-2309
Abstract 2328: Targeting angiogenesis: Anti-docking site peptides to Met receptor and nanotechnology
Authors: Cantelmo Anna Rita , Sogno Ilaria , Noonan Douglas M. , Focaccetti Chiara , Principi Elisa , Albini Adriana 
Published: August 2012

Abstract
The Met tyrosine kinase receptor is involved in different cell responses during development and pathological conditions. In cancer, Met can promote growth, invasion, angiogenesis and tumor metastasis following the interaction with its ligand, the hepatocyte growth factor (HGF). We decided to develop angiogenesis inhibitors that target the HGF pathway, impairing tumour neo-vascularization and metastatic spreading. We investigated the anti-angiogenic proprieties of a synthetic peptide mimicking the intracellular Met-tail, which was delivered into cells by fusion with the internalization sequences from Antennapedia or HIV-Tat. We are also trying to do peptide delivery by using carbon nanotubes. In order to evaluate the effect of Met-derived inhibitors on angiogenesis, we treated HUVEC with peptides and we evaluated their ability to interfere with HGF-induced proliferation, migration and morphogenesis of endothelial cells in vitro and angiogenesis. Kaposi's sarcoma (KS), the most frequent neoplasia in patients with AIDS, which originates from endothelial origin and is highly vascularized, shows features compatible with the biological properties of HGF. We used KS as tumour model to test the effect of peptides on tumour growth in vivo. We found that the peptides inhibited ligand-dependent endothelial cell proliferation, migration and morphogenesis in vitro and interfered with HGF-dependent downstream signalling. In vivo, the peptides inhibited HGF-induced angiogenesis and Kaposi's sarcoma tumour growth. We also demonstrated that diacylglycerol kinases (DGK) contribute to the malignant phenotype of KS. The data obtained show that the peptides impair angiogenesis triggered by HGF, suggesting the use of anti-docking site compounds as therapeutic agents to interfere with the angiogenesis process. The development of angiogenesis inhibitors and the identification of new intracellular transducers effective in the high vascularised KS cells, open the possibility of a combination therapy that concomitantly interferes with tumour neo-vascularization and the malignant properties of KS.
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 2328. doi:1538-7445.AM2012-2328
Abstract 2333: Serotonin: A known neurotransmitter functions as an angiokine to support cancer progression
Authors: Zamani Ali , Roy Anshu , Zhai Ling , Maxuitenko Yulia , Li Rongbao , Qu Zhican 
Published: August 2012

Abstract
Platelet aggregation leads to significant serotonin release from its major storage and results in increasing of serotonin levels at injury site and thrombotic tumor environment. Many studies have shown that platelet activation plays a crucial role in tumor progression; however, the role of serotonin in angiogenesis and tumor progression has not been well studied. In this study, we have tested the hypothesis that 5-HT promotes angiogenesis, and antagonizing 5-HT activity has anti-angiogenic benefit in controlling tumor growth. Real time PCR and western blot studies showed that endothelial cell expressed 5-HT receptor 1B (HTR1B) in higher level than other 5-HT receptors. Endothelial cell proliferation and tube formation were significantly affected by blocking HTR1B and the cAMP and IP1 assays have revealed the HTR1B as the inhibitory type of GPCR. Stimulation of endothelial cell with 5-HT or HTR1B agonist has led to activation of two individual signaling pathways: ERK and Akt / mTOR. In further studies, p70S6K was recognized as the merging point of these signaling. These kinases have been also activated by known angiogenic factors (VEGF and FGF) but the mechanism of activation was different from serotonin and it was through their tyrosine kinase receptors. In contrast, pretreatment of endothelial cell with a selective HTR1B antagonist have led to blockade of the 5-HT induced kinases’ activation. We also demonstrated angiogenic promoting activity of 5-HT with a mouse Matrigel plug (in vivo angiogenesis model system) and antiangiogenic potential of antagonists against HTR1B with an ex vivo tumor angiogenesis model (xenograft CAM assay) and xenograft mice model of human ovary cancer (SKOV-3). Selective HTR1B antagonist displayed the synergistic effect (combination index analysis) in blocking tumor-induced new blood vessel formation when it was applied in combination with Sutent (VEGFR2 antagonist). HTR1B antagonist also showed preclinical efficacy in the xenograft model of human ovary cancer by reducing over 50% in tumor size and blood vessel density marker.The results of this study enhanced our understanding of the serotonin-signaling pathway in human endothelial cells during angiogenesis. This research also revealed the potential of 5-HT signaling as the new target for antiangiogenic development.
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 2333. doi:1538-7445.AM2012-2333
Abstract 2342: Identification of oncogenes and tumor suppressor genes using immortalized lung bronchial epithelial cells and small airway epithelial cells
Authors: Gao Boning , Huang Chunxian , Girard Luc , Gazdar Adi F. , Shay Jerry W. , Minna John D. 
Published: August 2012

Abstract
We have immortalized human normal proximal bronchial epithelial cells (HBECs) for the study of lung tumors arising in the central compartment of the lung, and now have over 30 of these strains (growing in defined KSFM media) including many isogenic derivatives with various oncogenic changes (Can Res 2004, Can Res 2006). We have extended this by immortalizing normal distal (small airway) epithelial cells that serve as models for the study of tumors arising in the peripheral compartment of the lung. Using Cdk4 and hTERT exogenous expression vectors (as used for HBECs) and serum free defined media, we have immortalized (N= 19) human small airway epithelial cells (HSAECs) from peripheral lung. We have characterized the HBECs and HSAECs and found they have the property of lung basal /stem cells. In the current study, we compared the genome-wide RNA expression profile of HBECs/ HSAECs with 108 lung tumor cell lines and identified a panel of genes that are differentially expressed in these two cell types. We found ∼ 1200 genes that are 2 fold over expressed in tumor cells lines compared with HBECs/HSAECs (p ≤ 0.005). Many known lung tumor oncogenes such as members in cancer/testis (CT) antigen families (XAGE/GAGE/MAGE), proliferation-promoting E2F2 transcription factors, and Kinesin family are over-expressed in tumor lines validating the comparison strategies. In addition, we found genes that had been shown to be involved in other types of tumors but had not been reported in lung tumors. Importantly, we found several genes that had not been implicated as oncogenes previously, thus these are potential novel oncogenes for lung tumor transformation. We also found ∼1300 genes that are 2 fold over expressed in HBECs/HSAECs compared with tumor cell lines (p≤ 0.006). Many of the genes are lung basal cell markers (Keratin and Laminin family members) or known tumor suppressor genes (p53 binding genes and metallothionein genes) as expected. Like in the case of tumor specific genes, we found several genes that had not been reported functioning in the inhibition of tumor transformation. Thus, these are candidate tumor suppressor genes. The current study showed that the immortalized HBEC and HSAECs are ideal models for the discovery of novel oncogenes and tumor suppressor genes.
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 2342. doi:1538-7445.AM2012-2342
Abstract 2353: Therapeutic effect of cilengitide in combination with CKD-602, a campothecin derivative, against experimental glioblastoma
Authors: Kim Young-Hoon , Park Judy , Lee Jin Kyung , Kim Bokyong , Choi Seung Ah , Phi Ji Hoon , Park Chul-Kee , Kim Seung-Ki , Kim Chae-Yong 
Published: August 2012

Abstract
The prognosis and the clinical course for glioblastoma patients remain dismal in spite of various multidisciplinary approaches of treatment, such as concurrent chemoradiotherapy with temozolomide. Especially, the resistance to temozolomide of primary or recurrent glioblastoma is the significant obstacle to the cure of this tumor. In the present study, we evaluated the in vitro and in vivo antitumor effect of cilengitide in combination with CKD-602, a camptothecin derivate, for experimental glioblastoma. The combination treatment with cilengitide and CKD-602 enhanced the cytotoxic effects to the glioblastoma cell lines, including U87MG and U251MG and increased the proportion of apoptosis of the tumor cells, compared with the monotherapy with either drug. Nude mice with established U87MG glioblastoma were assigned to the 4 groups; control group (injection with saline only), 2 cilengitide group (injection with a dose of cilengitide at 2 mg/mL), CKD-602 group (injection with a dose of CKD-602 at 2 mg/mL), and combination group. In animals with combination therapy, the significant reduction of tumor volume was demonstrated (p &lt; 0.05). The immunohistochemistry with CD31 and Annexin-V showed that this synergistic effect was caused by the decrease of angiogenesis by cilengitide and the increase of apoptosis by CKD-602. Cilengitide in combination with CKD-602 could be an alternative treatment option for glioblastoma. Keywords; glioblastoma; cilengitide; CKD-602; angiogenesis; apoptosis
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 2353. doi:1538-7445.AM2012-2353
Abstract 2354: A neural origin for intracranial germ cell tumors
Authors: Tan Chris 
Published: August 2012

Abstract
Intracranial germ cell tumours (GCTs) are thought to arise from germ cells that aberrantly migrate to the brain during embryogenesis. In normal development, germ cells migrate from the hindgut towards the gonads. GCTs are found in several regions outside of the gonads and all of these are all thought to be midline structures. Therefore, the observation that GCTs occur in midline structures, and that normal germ cells migrate along the midline forms the basis of the current hypothesis for their formation. All GCTs regardless of location also share similar histology. Intracranial GCTs often occur in the ventral midline, such as the pineal and suprasellar regions. However, we challenge this model. We suggest that intracranial GCTs arise from endogenous neural progenitors in the brain rather than from misplaced germ cell progenitors. Neural stem cells have the potential to become pluripotent when Oct4 is activated. When these cells are transplanted into SCID mice they form teratomas, a type of GCT. We postulate that if only one gene is required to trigger formation of a GCT from a brain cell, that it is reasonable to suggest this as a more likely mechanism for GCT development. Oct4 is expressed in the brain until E13.5, so a delay in Oct4 silencing may allow pluripotent cells to form these tumours. Using doxycycline-dependent Oct4-expressing transgenic mice, we have shown that expression of Oct4 allows neural tissue to form teratomas. We have also surveyed the current literature which reveals that many GCTs also occur in all regions of the brain.
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 2354. doi:1538-7445.AM2012-2354
Abstract 2368: Unbiased quantitative assessment of Her-2 expression of circulating tumor cells in patients with metastatic and non metastatic breast cancer
Authors: Pierga Jean-Yves , Ligthart Sjoerd T. , Bidard François-Clement , Decraene Charles , Bachelot Thomas , Delaloge Suzette , Brain Etienne , Campone Mario , Viens Patrice , Terstappen Leon WMM 
Published: August 2012

Abstract
Circulating tumor cells (CTC) can provide the basis for a real-time liquid biopsy and may guide the use of targeted therapies. We report on unbiased quantification of Her-2 protein expression of CTC. Her-2 assessment of CTC was performed using the CellSearch® system in 103 metastatic (M1) and 88 non metastatic (M0) breast-cancer patients. Digital images of Cytokeratin-PE, DAPI, CD45-APC, and Her-2-FITC from these samples were stored. Expression of Her-2 on CTC was determined by manual review and an automated algorithm using Her-2-FITC fluorescence of leukocytes to determine the Her-2-expression threshold in each sample. Her-2 expression of CTC varied greatly within and between patients compared to Her-2 expression of leukocytes. In M1 patients, a threshold of 75% of Her-2 positive CTC in patients with &gt;5 CTC showed a relatively low discrepancy rate between the primary tumor and CTC Her-2 status. Applying this threshold, 9% of M1 patients with Her-2 negative primary tumors had Her-2 positive CTC status and 29% of M1 patients with Her-2 positive primary tumors had Her-2 negative CTC status. No Her-2 discrepancy was observed between CTC and primary tumor in M0 patients. Our findings demonstrate the feasibility of real-time quantitative and reproducible assessment of treatment targets on CTC, opening a path towards personalized treatment. Her-2 expression is heterogeneous among CTC within each patient. Overall, M1 patients with Her-2 positive primary tumors exhibited Her-2 negative CTC frequently, whereas discrepancies in Her-2 status were limited in other clinical settings.
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 2368. doi:1538-7445.AM2012-2368