bluuebunny/crossref_metadata_2025_split huggingface dataset:
SIGWEB annual report
Authors: Harper Simon 
Published: August 2012

The last year has been an exciting one for SIGWEB. From the sponsorship of the large Web Science Conference, to that of the small Social Network Working Group; from the increase in student travel sponsorship (to $25,000pa), to our increasing volunteer effort; the SIG has been at work at all levels of our domain.
We have forged links with multiple (≈20) conferences and workshops across our field, building a better website for our members, changing our bylaws to cement our relationship with our conferences, while still maintaining our low membership dues. In short, it has been an active and productive year.
However, we have faced some challenges too, with a small reduction in membership numbers (to 535). But, we have an increasing funds balance (to $560,000), and are still increasing the amount we have to spend on each member, from $590 last year to $618 this year; with member benefits of: Reduced rates at SIGWEB sponsored, co-sponsored, and co-operating events; Free access to ACM DL content of events sponsored by SIGWEB; Reduced subscription rates to New Review of Hypermedia and Multimedia; Free subscription to the SIGWEB members email list, with calls, advance and final event programs; and news of interest to the community posted regularly; we still have an excellent membership offering.
In short SIGWEB has successfully expanded its range of conference sponsorships, is working hard on membership and volunteer development and benefits, and is financially healthy with a solid leadership.
Abstract 1084: Naturally occurring variants of human α9 nicotinic receptor differentially affect bronchial cell proliferation and transformation
Authors: Chikova Anna , Grando Sergei 
Published: August 2012

Abstract
Isolation of polyadenilated mRNA from human immortalized bronchial epithelial cell line BEP2D revealed the presence of multiple isoforms of RNA coded by the CHRNA9 gene for α9 nicotinic acetylcholine receptor (nAChR). BEP2D cells were homozygous for the rs10009228 polymorphism encoding for N442S amino-acid substitution, and also contained mRNA coding for several truncated isoforms of α9 protein. To elucidate the biologic significance of the naturally occurring variants of α9 nAChR, we compared the biologic effects of overexpression of full-length α9 N442 and S442 proteins, and the truncated α9 variant occurring due to a loss of the exon 4 sequence that causes frame shift and early termination of the translation. These as well as control vector were overexpressed in the BEP2D cells that were used in the assays of proliferation rate, spontaneous vs. tobacco nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced cellular transformation, and tumorigenicity in cell culture and mice. Overexpression of the S442 variant significantly increased cellular proliferation, and spontaneous and NNK-induced transformation. The N442 variant significantly decreased cellular transformation, without affecting proliferation rate. Overexpression of the truncated α9 significantly decreased proliferation and suppressed cellular transformation. These results suggested that α9 nAChR plays important roles in regulation of bronchial cell growth by endogenous acetylcholine and exogenous nicotine and susceptibility to NNK-induced carcinogenic transformation. The biologic activities of α9 nAChR may be regulated at the splicing level, and genetic polymorphisms in CHRNA9 affecting protein levels, amino-acid sequence and RNA splicing may influence the risk for lung cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1084. doi:1538-7445.AM2012-1084
Abstract 109: CSE1L, a 20q gain passenger that drives colorectal adenoma to carcinoma progression
Authors: Sillars-Hardebol Anke H. , Carvalho Beatriz , Belien Jeroen A.M. , de Wit Meike , Delis-van Diemen Pien M. , Tijssen Marianne , van de Wiel Mark A. , Ponten Fredrik , Meijer Gerrit A. , Fijneman Remond J. A. 
Published: August 2012

Abstract
Background ‘Driver genes’ are defined as genes that promote the tumorigenic process upon acquirement of somatic alterations. Gain of chromosome 20q is an important factor in the progression of colorectal adenomas to carcinomas. Previously we identified TPX2 and AURKA as two genes that drive 20q amplification in colorectal adenoma to carcinoma progression, based on correlation of mRNA and protein expression levels with 20q DNA copy number status while functionally influencing cancer processes. These findings are consistent with the hypothesis that the selection advantage imposed by 20q gain in colorectal adenoma to carcinoma progression is achieved by gain-of-function of multiple cancer-related genes at chromosome 20q, rather than affecting a single driver gene. In addition to TPX2 and AURKA, other 20q genes such as CSE1L may further contribute to tumor progression. Aim We here investigated whether CSE1L is another 20q located gene that drives colorectal adenoma to carcinoma progression, in a 20q gain-dependent manner. Methods Functional effects of CSE1L on cell viability, anchorage-independent growth and invasion were investigated upon gene knockdown using the SW480 colorectal cancer cell line. CSE1L protein expression levels were examined by immunohistochemical evaluation of tissue microarrays containing a series of colorectal adenoma and carcinoma samples, which were characterized by genome-wide (microarray-based) DNA and mRNA profiling. Results CSE1L knockdown affected cell viability and anchorage-independent growth. CSE1L mRNA expression levels correlated with chromosome 20q DNA copy number status. However, CSE1L protein expression was not associated with 20q gain, although its expression was increased in carcinomas compared to adenomas. Conclusion CSE1L appears to be a driver of colorectal tumor progression based on its functional effects combined with increased protein expression levels in carcinomas compared to adenomas. However, the lack of correlation between CSE1L protein expression levels and 20q DNA copy number status in colorectal adenoma to carcinoma progression implies that CSE1L is merely a passenger rather than a driver of chromosome 20q amplification, suggesting that CSE1L protein levels are subject to post-transcriptional regulation in a 20q gain-independent manner.
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 109. doi:1538-7445.AM2012-109
Abstract 1090: Impact of CXCL1/CXCR2 signaling in ovarian cancer proliferation
Authors: Dong Yuanlin , Kabir Syeda M. , Son Deok-Soo 
Published: August 2012

Abstract
Introduction: Chemokine network plays a critical role in the development and progression of cancer. Human ovarian tumors express chemokine CXCL1 and its receptor CXCR2, but its role in ovarian cancer development and progression remains unclear. In this study, we investigate whether CXCL1/CXCR2 have functional significance in ovarian cancer cell proliferation. Methods: CXCR2 was overexpressed by stable transfection into the human ovarian surface epithelial cancer cell lines A2780, OVCAR3, and SKOV3. The influence of CXCL1 and CXCR2 on cell proliferation, cell cycle progression, and changes in related proteins and gene expression were determined by using confocal image analysis, MTT assay, Western blotting, flow cytometry, and PCR array. Results: CXCR2 was mainly expressed on the cell surface and intracellular localization, and these expressions were profoundly enhanced in CXCR2 overexpressed cell lines when compared to controls. CXCR2 significantly increased the proliferation of A2780, OVCAR3 and SKOV3 cells in a time-dependent manner, and these increases were abolished by the CXCR2 inhibitor, SD 225002. Furtermore, CXCR2-induced cancer cell proliferation was suppressed by Gefitinib, an inhibitor of epidermal growth factor receptor (EGFR), indicating crosstalk between CXCR2 and EGFR in ovarian cancer cell proliferation. CXCR2 induced phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) and NF-kappa B, probably contributing to ovarian tumor growth and metastatic progression. CXCL1 significantly stimulates the cell proliferation in CXCR2 overexpressed cell lines, and the stimulations were substantially blocked by the ERK1/2 inhibitor, PD 98059, further confirming the involvement of MAPK signaling. CXCR2 reduced cell cycle arrest in the G0-G1 phase and increased the cell population in the S and G2-M phase, and these changes were associated with enhanced expression for CDK6, a G1-S cell cycle transition regulatory gene. Chemokine specific PCR array revealed that CXCR2 enhances proinflammatory chemokines CCL2, CXCL1, CXCL2, CXCL3, and CXCL6, suggesting that CXCR2 accelerates proinflammatory tumor microenvironment to provide the suitable condition for ovarian cancer progression. Conclusions: Taken together, this study demonstrated that CXCL1/CXCR2 signaling plays critical roles in ovarian cancer growth and progression through the activation of ERK1/2 and NF-kappa B. Thus, CXCL1/CXCR2 signaling may be important in the pathogenesis of ovarian cancer, providing a basis for the therapeutic targets in ovarian cancer 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 1090. doi:1538-7445.AM2012-1090
Abstract 1091: Cannabinoids inhibit epidermal growth factor receptor transactivation in lung cancer cells
Authors: Moody Terry W. , Mantey Samuel , Jensen Robert T. , Wink David , Mukhopadhyay Partha , Pacher Pal 
Published: August 2012

Abstract
The cannabinoid receptors CB1 and CB2 are present on non-small cell lung cancer (NSCLC) biopsy specimens (Preet et al., 2011, Cancer Prev. Res. 4:65). CP55,940 and Win55,212-2 are mixed agonists which stimulate CB1 and CB2 cannabinoid receptors. G-protein coupled receptors (GPCR) for pituitary adenylate cyclase activating polypeptide (PACAP) regulate epidermal growth factor receptor (EGFR) tyrosine phosphorylation in NSCLC cells. Here the ability of cannabinoids to alter EGFR transactivation was investigated. PACAP stimulated EGFR tyrosine phosphorylation (PY1068) 4-fold using NCI-H838 and H1299 cells. CP55,940 and Win55,212-2 inhibited the ability of PACAP to increase EGFR tyrosine phosphorylation in lung cancer cells. By Western blot, cell lines NCI-H838 and NCI-H1299 had both CB1 and CB2 receptors. PACAP increased cAMP levels in NCI-H838 cells and CP55,940 inhibited the increase in cAMP caused by PACAP. In contrast, PACAP increased cytosolic Ca2+ in lung cancer cells, but CP55,940 did not alter the ability of PACAP to increase calcium in lung cancer cells. These results suggest that CP55,940 may inhibit adenylyl cyclase activity but not phosphatidylinositol turnover caused by addition of PACAP to lung cancer cells. Previously we found that PACAP increased tyrosine phosphorylation of focal adhesion kinase, paxillin and ERK in lung cancer cells (Moody et al., 2002, Reg. Peptides 109:135). CP55,940 inhibited the increase in tyrosine phosphorylation of focal adhesion kinase, paxillin and ERK caused by PACAP addition to lung cancer cells. Also, CP55.940 and Win55,212-2 inhibited the growth of NCI-H1299 and NCI-H838 cells. CP55,940 potentiated the growth inhibitory effects of gefitinib, an EGFR tyrosine kinase inhibitor. These results indicate that cannabinoids inhibit EGFR transactivation in lung cancer cells and potentiate gefitinib cytotoxicity.
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 1091. doi:1538-7445.AM2012-1091
Abstract 11: A requirement for SOCS-1 and SOCS-3 phosphorylation in BCR-ABL-mediated transformation
Authors: Chen Jilong , Qiu Xiaoxue , Guo Guijie , Chen Ke 
Published: August 2012

Abstract
Previous studies have demonstrated that constitutive activation of JAK/STAT signaling is required for efficient transformation by the Abelson murine leukemia virus (A-MuLV), which expresses v-Abl oncoprotein. Importantly, there is increasing evidence that deregulation of the JAK or STAT activity plays a critical role in BCR-ABL-induced malignant transformation. SOCS-1 and SOCS-3 are inhibitors of JAK-STAT pathway and as such are involved in a negative feedback loop of cytokine signaling. However, the mechanism by which Abl oncogene bypasses SOCS inhibitory regulation remains poorly defined. Here, we found that co-expression of BCR-ABL with SOCS-1 or SOCS-3 resulted in tyrosine phosphorylation of these SOCS proteins. Interestingly, tyrosine-phosphorylated SOCS-1 was detected in three of five primary CML samples which express BCR-ABL. BCR-ABL-dependent phosphorylation of SOCS-1 and SOCS-3 occurred mainly on Tyr 155 and Tyr 204 residues of SOCS-1, and Tyr 221 residue of SOCS-3. Phosphorylation of these SOCS proteins was associated with its binding to BCR-ABL, and this interaction was disrupted by mutation of the sites of SOCS phosphorylation. We demonstrated that BCR-ABL-dependent phosphorylation of SOCS-1 and SOCS-3 alters their inhibitory effects on the activation of JAK1 and JAK2 and thereby enhances JAK-STAT signaling. Moreover, disrupting the tyrosine phosphorylation of SOCS-1 or SOCS-3 promotes K562 leukemic cells to undergo apoptosis and blocks tumor formation in mouse model. Together, these results reveal a requirement for tyrosine phosphorylation of SOCS-1 and SCOCS-3 in BCR-ABL-mediated transformation in the presence of these SOCS proteins.
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 11. doi:1538-7445.AM2012-11
Abstract 110: Role of CARD 10 mediated NF-kB activation in colorectal carcinoma cells
Authors: Bu Rong , Ahmed Maqbool , Bavi Prashant , Sultana Mehar , Al-Haqawi Wael , Uddin Shahab , Al-Kuraya Khawla S. 
Published: August 2012

Abstract
Colorectal carcinoma is the fourth most common cancer in men and the third in women worldwide, accounting for 8% of all cancer deaths. NF-κB gene plays a role in tumorgenesis through the transcriptional activation of genes associated with cell proliferation, angiogenesis, metastasis, tumor promotion, inflammation and suppression of apoptosis. NF-κB protein activation, defined as nuclear expression of NF-κB by immunohistochemistry was an independent prognostic marker for poor survival. CARD10 gene is known positive regulator of the NF-κB activation pathway and can activate the NF-κB activity. CARD10 is an enzyme that is encoded by the CARD10 gene and it associates with IKK complex resulting in NF-κB activation. Considering the potential therapeutic utility of targeting NF-κB and its key modulators, we previously studied CARD10 genetic alterations and immunohistochemical expression of CARD10 in a large cohort cases1. CARD10 protein expression associated significantly with NF-κB activation, and CARD10 amplification was significantly associated with CARD10 protein expression and presence of distance metastasis. To extend and confirm our clinical finding, we performed in vitro studies using a panel of CRC cell lines to investigate the biological role of CARD10 alterations in CRC carcinogenesis. Our data showed that TNF-α treatment caused efficient translocation of p56 in CARD 10 muatation harboring cell line -DLD-1 cells to nucleus as compared to HCT-15 cells. Furthermore, the luciferase activity was significantly higher in CARD 10 amplified HCT-116 cells as compared to DLD1 and HCT-15 cells which carry normal CRAD10 gene copy number after 48 hours of transfection with an NF-κB reporter. In addition, it was also observed that the formation of colonies was significantly higher in HCT-116 as compared to DLD-1 and HCT-15. Finally CARD 10 siRNA transfection knocked down the expression of CARD10 and abrogated the expression of NF-κB, and resulted in apoptosis through activation of caspase-3. These data suggest that CARD10 mutation and amplification mediated NFκB activation play an important role in cellular transformation of CRC cells. Thus, the study raises the possibility that inhibition of CARD10 might have significant therapeutic value in CRC. Reference: 1: Jehad Abubaker, Prashant Bavi, Zeenath Jehan, Maqbool Ahmed, Wael Al-Haqawi, Mehar Sultana, Sarita Prabhakaran, Nasser Al-Sanea, Alaa Abduljabbar, Luai H Ashari, Samar Alhomoud, Fouad Al-Dayel, Shahab Uddin, Khawla S. Al-Kuraya. Clinicopathological significance of CARD10 alterations in Middle Eastern colorectal cancer. 102nd AACR Annual Meeting, April2-6, 2011, Orlando, Florida.
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 110. doi:1538-7445.AM2012-110
Abstract 1110: Effect of miR-29 on cisplatin sensitivity of ovarian cancer cells
Authors: Yu Pei-Ning , Lin Wen-Chi , Kuo Chih-Chi , Huang Rui-Lan , Yan Ming-De , Shih Yu-Lueng , Chou Yu-Ching , Lai Hung-Cheng , Lin Ya-Wen 
Published: August 2012

Abstract
In clinical practice, the main dilemma to a successful ovarian cancer therapy is the development of drug resistance. The mounting evidence demonstrated that microRNAs (miRNAs) not only controlled cell proliferation, invasion and metastasis but also therapeutic resistance of ovarian cancer cell. Recently, we isolated CP70sps(CP70 side population spheres) from CP70 ovarian cancer cell line and proved that CP70sps exhibited more resistant to cisplatin than CP70. This phenomenon was correlated to other study which supported that side population of cancer cells was responsible for chemoresistance. In this study, we compared the expression of miRNAs between CP70sps and CP70 to investigate the role of miRNAs in cisplatin resistance of ovarian cancer cells. Our miRNA array and quantitative RT-PCR data showed that CP70sps expressed lower level of miR-29a/b/c family than CP70 cells and CP70sps4wks cells which were repopulation of CP70sps in attached condition. After knockdown of miR-29a/b/c family by miRNA inhibitors, reduction of miR-29a/b/c family enhanced cisplatin resistance of CP70 cells. However, there was no effect on cell cycle and proliferation rate in both CP70 cells and A2780, a parental cisplatin-sensitive cell line of CP70 cells. Downregulation of miR-29a/b/c family contributed cells to escape cisplatin-induced cell death through COL1A1 upregulation. Moreover, reduction of miR-29a/b/c increased phosphorylation of ERK1/2 and GSK3β to transduce survival signaling and reduced active form casepase-9 to avoid cell apoptosis. Furthermore, we found that either ectopic expression of miR-29 alone or combination of miR-29 with cisplatin treatment efficaciously reduced tumorigenicity of CP70 cells in immunodeficiency mice. Finally, we ascertained that the ovarian cancer patients with high expression of miR-29a had better overall survival rate. Taken together, our data demonstrated that the miR-29 family was a sensitizer for cisplatin treatment and might be associated with tumorigenecity of ovarian cancer cells.
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 1110. doi:1538-7445.AM2012-1110
Abstract 1130: API 31510 induced shift in mitochondrial metabolism in cancer cells is characterized by increased mitochondrial efficiency and induction of apoptosis
Authors: Jing Enxuan , Vishnudas Vivek , Jimnenez Joaquin J. , Narain Niven R. , Sarangarajan Rangaprasad 
Published: August 2012

Abstract
API 31510 is an ubidecarenone-based small molecule currently in late stage clinical development for skin cancers and early stage for solid tumors. Mechanism of action studies demonstrate that there is induced metabolic shift that occurs via modulation of the pentose phosphate shunt. The current study focused on delineating further insight into the relationship of mitochondrial metabolism and API 31510 induced apoptosis on different cancer cell lines. Use of Berg Interrogative Biology™ Platform of high thorough-put “omic” data demonstrated presence of coordinated alterations on gene expression and substrate metabolism in the cells in response to treatment with API 31510. Detection of apoptotic responses in different cancer cell lines revealed a significant elevation of different markers such as Bcl2, BcL-xL, BIRC3, and GADD45. Hence, the treatment induced significant increases in the intrinsic apoptosis networks in pancreatic (PaCa-2), breast (SKBr3), and liver (Hep3B) cancer cell lines. Furthermore, treatment with API 31510 is associated with increase in the ATP/oxygen consumption rate (OCR) ratios, suggesting increased mitochondrial efficiency in API 31510 treated cancer cells. Conversely, in normal fibroblasts, aortic smooth muscle, cardiomyocytes, and liver cells, the cells exhibited a more homeostatic phenotype and were not adversely affected by administration of API 31510. This observation suggests that the oncogenic phenotype secondary to mitochondrial dysfunction alters the metabolic machinery in a manner that confers an evasion of intrinsic apoptotic potential in cancer. Increased ATP/OCR is accompanied by altered intracellular reactive oxygen species (ROS) production in cancer cell lines. Taken together, the data suggest that the data demonstrate that treatment with API 31510 is associated with induction of significantly increased cell death triggered by increased mitochondrial efficiency, altered ROS and apoptosis activation in cancer cells.
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 1130. doi:1538-7445.AM2012-1130