bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract LB-242: Dissecting Cell Signaling Mediated by Multi-spanning Transmembrane Domain Association
Authors: Yin Hang 
Published: June 2012

Abstract
The association of protein transmembrane domains regulates many pivotal signal transduction pathways. Molecular recognition by polytopic membrane proteins is especially poorly understood due to their difficult preparation, characterization and analysis. Herein, we demonstrate a modular approach designed to study multi-spanning transmembrane domain association, using hydrophobic peptides representing individual transmembrane helices. Transmembrane helices have a high level of intrinsic stability due to the energetic requirement to sequester the polar backbone from the hydrophobic environment of the membrane causing them to adopt native-like structures in membrane-mimetic environments. Biophysical and biochemical experiments on individual transmembrane helices identified a novel protein-oligomerization hotspot for a representative membrane protein, latent membrane protein 1, and the key residue was confirmed as biologically relevant in the full-length protein. This generally applicable approach provides a novel strategy to study multi-spanning transmembrane proteins.
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 LB-242. doi:10.1158/1538-7445.AM2011-LB-242
Abstract LB-250: Establishment of a positive feedback between PGE2 and COX2 diverts DC differentiation into MDSCs and sustains their immunosuppressive functions in ovarian cancer
Authors: Obermajer Natasa , Muthuswamy Ravikumar , Lesnock Jamie , Edwards Robert P. , Kalinski Pawel 
Published: June 2012

Abstract
Myeloid-derived suppressor cells (MDSCs) are essential players in cancer-associated immune dysfunction. We report that the differentiation and functional stability of human monocytic MDSCs is driven by a single cancer-associated inflammatory mediator, prostaglandin E2 (PGE2), and depends on the establishment of a positive feedback between PGE2 and the key regulator of PGE2 synthesis, COX-2. PGE2 abrogates the differentiation of CD1a+ DC from monocytes, redirecting it towards CD14+CD33+CD34+ cells expressing all MDSC-associated suppressive factors: IDO, arginase, NOS2 and IL-10, and inducing their CTL-suppressive functions. Moreover, PGE2 promotes the expression of endogenous COX2 and autocrine secretion of PGE2 in MDSCs, establishing a positive feedback loop that stabilizes the MDSC phenotype. Undisturbed COX2 activity and persistent production of PGE2 by MDSCs, isolated from cancer patients, was required for their continued expression of CXCR4 and responsiveness to CXCL12. Moreover, PGE2 also proved to be the key factor promoting the production of CXCL12 in cancer microenvironment, a chemokine exerting multiple tumor-promoting effects either directly by acting on cancer cells or indirectly by inducing angiogenesis and recruiting other immunosuppressive cells, i.e. Tregs and pDCs. In accordance with the physiological role of PGE2 in the development and functional stability of human cancer -associated MDSCs, we observed that the frequencies of CD11b+ CD33+ MDSCs in the ovarian cancer (OvCa) ascites closely correlate with the local production of PGE2 and expression of COX2, while the OvCa ascites environment can promote the induction of MDSCs from differentiating monocytes in a COX2-dependent manner. Importantly. disruption of COX2-PGE2 feedback in fully-developed MDSCs isolated from cancer patients, using COX2 inhibitors or inhibitors of EP2/EP4-dependent PGE2 signaling, eliminates the production of all other suppressive factors and terminates the CTL-suppressive function of MDSCs as well as eliminates both the expression of CXCR4 on MDSCs and the production of CXCL12, highlighting the key role of PGE2 in the tumor-accumulation of immunosuppressive cells. The currently demonstrated key role of the positive COX2-PGE2 feedback loop in the differentiation and functional stability of MDSCs facilitates the targeting of MDSCs in cancer immunotherapy and facilitates the development of additional MDSC-targeting therapies.
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 LB-250. doi:10.1158/1538-7445.AM2011-LB-250
Abstract LB-260: Transcriptional silencing disrupts two levels of arginine biosynthesis in glioblastoma multiforme: a novel, targeted therapeutic strategy for high grade gliomas
Authors: Syed Nelofer , O'Neill Kevin , Hughes Mark , LoNigro Christiana , Lattanzio Laura , Szlosarek Peter , Roncaroli Federico , Crook Timothy 
Published: June 2012

Abstract
Background: Changes in the structure and expression of enzymes involved in key metabolic pathways (such as isocitrate dehydrogenase) have been identified in glial brain tumours. To seek novel candidate brain tumour suppressors, we have performed pharmacological methylation reversal.
Methods: Methylation reversal was performed in human GBM cell lines and primary explants using 5′ azacytidine (5′AZA), coupled with micro-array analysis, in GBM. Gene expression was analysed using qPCR and western blotting and by immunohistochemistry in clinical cases of supra-tentorial adult GBM. Methylation was analysed using methylation specific PCR and quantitative pyrosequencing.
Results: Both ASS1, which encodes arginino succinate synthetase, and arginino succinate lyase (ASL) are down-regulated in GBM. Down-regulation correlates with aberrant, neoplasia-specific methylation in the CpG island of each gene and expression is restored by demethylation. Arginine starvation produced by exposure to the arginine-depleting agent pegylated arginine deiminase induces an adaptive transcriptional up-regulation of both ASS1 and ASL which is blocked in GBM cells by methylation. Cells lacking ASS1 or ASL are sensitive to arginine deprivation and die by apoptosis when treated with arginine deiminsase. In clinical cases of de novo GBM, treated by surgical debulking in our institution, ASS1 was silenced in 13/60 cases and ASL in 3/60. These cases had no expression of the proteins, as seen by immunohistochemistry, together with aberrant CpG methylation.
Conclusions: Taken together, these results identify a novel treatment strategy and suggest that ADI-PEG20 warrants evaluation in phase 2 clinical trial in ASS1 negative GBM.
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 LB-260. doi:10.1158/1538-7445.AM2011-LB-260
Abstract LB-67: From Patient to Advocate
Authors: Ford Peg 
Published: June 2012

Abstract
Peg Ford is a living example of two causes that have become her passion: early detection of ovarian cancer and timely referral of patients into the care of a gynecologic oncologist. Before Ms. Ford's experience with ovarian cancer, she had mostly chosen alternative healing methods. Impressed and appreciative of the diversity of care the western medical system now offers, she was directed toward advocacy to spread awareness of the benefits of interweaving both types of care.
She chose to pursue advocacy for many reasons, but most importantly to put ovarian cancer at the forefront of medical doctors' minds. Early diagnosis is crucial to saving more women's lives. The overall survival rate for ovarian cancer for five years is only 45 percent, but when the cancer is diagnosed early, survival rates greatly improve to over 90 percent. Until there is a screening test for ovarian cancer, women must rely on the awareness of medical doctors in all fields. She strives to ensure that all women have a great understanding of their bodies and act as their own advocates to get care in a timely fashion.
Ms. Ford's poster outlines her journey to becoming an advocate. After discovering an innovative educational program, “Survivors Teaching Students: Saving Women's Lives,” created by the Ovarian Cancer National Alliance, she successfully launched the program at UCSD School of Medicine for Third Year Medical Students. The course brings ovarian cancer survivors right into the classroom to share their stories with the goal of increasing awareness of the symptoms and risk factors needed for the early detection of ovarian cancer. Her poster reflects the outstanding success of the program in two short years.
Seeing the need and opportunity to reach practicing medical doctors, she teamed up with the esteemed Dr. Afshin Bahador, Gynecologic Oncologist, to participate in his grand rounds at major hospital campuses. Her commitment to tell her story whenever the opportunity presents itself: as a guest speaker, facilitator, or writer for community outreach efforts, blossoms into a voice for the ovarian cancer community on a local, state, national, and international level. Her poster outlines her diverse advocacy efforts from DoD Funding, a Research Advocacy Network's 2010 Scholar at ASCO, as a member of the Core Planning Group of COCAP, as a consumer reviewer for The Cochrane Collaboration, and as an attendee of the Salzburg Global Seminar in Salzburg, Austria. With her appreciation for the advances in research, her poster highlight's patient advocates' roles as the bridge between the scientific/medical world to the patient community and to work hand-in-hand to advance research and impact change to better serve both communities.
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 LB-67. doi:10.1158/1538-7445.AM2011-LB-67
Abstract SY17-02: A systems approach to understanding tumor specific drug response
Authors: Akavia Uri David , Litvin Oren , Sanchez-Garcia Felix , Dylan Kotliar Helen C. , Kim Jessica , Garraway Levi A. , Pe'er Dana 
Published: June 2012

Abstract
Systematic characterization of cancer genomes has revealed a staggering complexity of aberrations among individuals, such that the functional importance and physiological impact of most tumor genetic alterations remains poorly defined. A major challenge involves the development of analysis methods to uncover biological insights from the data, including the identification of the key mutations that drive cancer and how these events alter cellular regulation.
We have developed Conexic, a novel Bayesian Network-based framework to integrate chromosomal copy number and gene expression data to detect to detect driver genes located in regions that are aberrant in tumors. The underlying assumption is that a driving mutation might be associated with a characteristic gene expression signature representing genes whose expression is modulated by the driver. Thus our score guided approach searches for genes that are both recurrently aberrant and associated with variance of expression patterns across tumor samples. This method not only pinpoints specific regulators within a large aberrant region, but also by associating drivers with gene modules whose expression vary with the driver, provides insight into the physiological roles of drivers and associated genes.
We demonstrated the utility of the CONEXIC framework using a melanoma dataset, our analysis correctly identified known drivers in melanoma (such as MITF) and connected these to many of their known targets, as well as the biological processes they regulate. In addition, it predicted multiple tumor dependencies TBC1D16 and RAB27A in melanoma and showed that tumors highly expressing these genes are dependent on the same gene for growth. Additionally, gene expression in the associated modules is altered following knockdown as predicted by our model. The identity of these drivers suggests that abnormal regulation of protein trafficking is important for cell survival in melanoma and highlights the importance of protein trafficking in this malignancy.
We also present more recent results of applying CONEXIC to additional cancers, including glioblastoma and ovarian cancers, as well as additional phenotypes including invasion and drug resistance. Together, these results demonstrate the ability of integrative Bayesian approaches to identify novel drivers with biological, and possibly therapeutic, importance in 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 SY17-02. doi:10.1158/1538-7445.AM2011-SY17-02
Abstract A13: Lineage-specific roles for the Ron receptor in prostate cancer
Authors: Paluch Andrew M. , Thobe Megan N. , Gray Jerilyn K. , Gurusamy Devikala , Waltz Susan E. 
Published: June 2012

Abstract
Prostate cancer is one of the leading causes of cancer-related death among men in the United States due, in part, to its aggressiveness and resistance to therapy following a remission period. Receptor tyrosine kinases are emerging as potential therapeutics in prostate cancer. One of these receptors, the Ron receptor tyrosine kinase, has been shown to be overexpressed in a variety of cancers where it modulates many cellular functions relevant to cancer such as invasion, inflammation, angiogenesis, and proliferation. Ron is expressed primarily on epithelial cells and macrophages, which are both important in regulating the prostate tumor microenvironment. Our laboratory has shown recently that crossing mice lacking the Ron receptor (Ron TK−/−) to TRAMP+ mice, which develop prostate adenocarcinomas by 30 weeks of age, leads to a significant decrease in prostate tumor mass, tumor vascularization, and proangiogenic chemokine secretion relative to TRAMP+ control mice. In addition, we have shown that loss of Ron in the myeloid lineage (monocytes and granulocytes) leads to decreases in prostate tumor establishment using an orthotopic model of prostate cancer. Given this, we therefore wished to understand what role the Ron receptor plays in specific cell types relevant to prostate cancer progression. By knocking out Ron in the prostate epithelium or myeloid lineage (monocytes, macrophages, and granulocytes) and crossing these mice onto a TRAMP background, we hope to investigate the effect of lineage-specific loss of Ron in mediating prostate cancer development and progression. We hypothesize that Ron receptor signaling in the prostate epithelium and in myeloid cells promotes prostate tumorigenesis via interdependent mechanisms. By understanding the interdependent mechanisms of Ron signaling in the prostate epithelium and myeloid lineage, our studies will identify a potential novel signaling pathway, its combined and cell-type specific role in regulating prostate tumorigenesis, and suggest novel avenues for the development of new therapies.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr A13.
Abstract A19: The effect of sunitinib on the production of cytokine in H460 tumor-bearing SCID mice.
Authors: Tsai Yung-Jen , Huang Yuan-Jen , Hong Le-Mei , Chang Jia-Ming 
Published: June 2012

Abstract
Background: systemic inflammation is occurred patients with many different type of cancer which is associated with disease progression and therapeutic efficacy. The aim of this study was to investigate whether Interleukin 5 (IL-5), an interleukin produced by innate immune cells, and Interferon-gamma (INF-γ), the dimerized soluble cytokine produced by natural killer cells, may be stimulated by sunitinib in H460 tumor-bearing SCID mice.
Methods: NCI-H460, a lung carcinoma cell line was inoculated in SCID mice subcutaneously. The H460 tumor-bearing mice were treated with sunitinib at a dose of 40 mg/kg by gavage one per day for 15 days. At the end of treatment, mice were sacrificed and blood was withdrawn for cytokine analysis by cytometric bead-based array (CBA).
Results: results appeared that the tumor growth was inhibited by sunitinib treatment to 69.97 % inhibition. And with analysis of IL-5 and INF-γ, end levels of IL-5 and INF-γ were significantly enhanced which is correlated to sunitinib treatment.
Summary: The results indicated that analyzing IL-5 and INF-γ in treatment might be used as prognosis biomarkers for cancer treatment.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr A19.
Abstract A28: The link between the metabolic effects of nuclear receptor (NR) modulators and anticarcinogenic properties on leukemia cancer cells can be revealed through studying the Warburg effect
Authors: Attia Ramy R. , Min Jaeki , Guy R. Kiplin 
Published: June 2012

Abstract
The Warburg effect is the observation that most cancer cells predominantly produce energy by a high rate of glycolysis followed by lactic acid fermentation in the cytosol, rather than by a comparatively low rate of glycolysis followed by aerobic oxidation of pyruvate in mitochondria. Genetic studies in humans and rodents support the notion that metabolic enzymes controlling glucose metabolism can directly contribute to carcinogenesis. Current knowledge of nuclear receptor (NR) signaling networks indicates that NRs control a wide variety of metabolic processes by regulating the expression of genes encoding key enzymes, transporters, and other proteins involved in metabolic homeostasis. Thus, a better understanding of the mechanistic links between cellular metabolism control by NRs and cancer cells' growth control may ultimately lead to better treatments for human cancer. We created a library of 134 NR modulators including compounds targeting the estrogen receptor (ER), androgen receptor (AR), farnesoid X receptor (FXR), peroxisome proliferator-activated receptor (PPAR), retinoic acid receptor (RAR), retinoid X receptor (RXR), glucocorticoid receptor (GR), mineralocorticoid receptor (MR), liver X receptor (LXR), thyroid receptor (TR), and pregnane X receptor (PXR). We used high-throughput assays to measure cell viability, apoptosis, and cell proliferation of leukemic cell lines after treatment with this library. Afterwards, compounds which highly induced apoptosis and inhibited cell proliferation were picked for further investigation of their mechanism of action. We linked the effect of those compounds on apoptosis to their effect on lactate levels. In addition, we tested the effect of these compounds on the activity of pyruvate dehydrogenase complex (PDC) which catalyzes the irreversible oxidative decarboxylation of pyruvate into acetyl-CoA an important step in commitment of glucose into full oxidation rather than glycolysis, PDH dipstick assay was used for this purpose. Of the 134 nuclear receptors modulators that we have tested, nine compounds induced significant apoptosis in Jurkat cells. These compounds mainly targeted ER and RAR. On the other hand, only six compounds from this list significantly reduced the lactate levels in Jurkat cells. Finally, the compounds modulating the RAR pathway were the only compounds that showed significant effects on PDC activity. This work may open a door to further explore the RAR modulators as strong potential anticarcinogenic agents.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr A28.
Abstract A45: The tumor suppressor role of ARID1A in gynecologic cancer
Authors: Guan Bin , Wang Tian-Li , Shih le-Ming 
Published: June 2012

Abstract
ARID1A (BAF250A), a gene participating in the formation of a BRG1 SWI/SNF chromatin remodeling complex, has emerged as a potential tumor suppressor because of its frequent inactivating mutations in gynecological cancer (approximately 50% of ovarian clear cell and 30% of ovarian endometrioid carcinomas). The mutation is associated with loss of protein expression as assessed by immunohistochemistry. In this study, we analyzed ARID1A expression in a wide variety of carcinomas to determine the prevalence of ARID1A inactivation in carcinomas using immunohistochemical staining. Immunoreactivity was not detected in 36 (3.6%) of 995 tumors. Uterine low-grade endometrioid carcinomas showed a relatively high-frequency loss of ARID1A expression, as 15 (26%) of 58 cases were negative. Mutational analysis showed 10 (40%) of 25 uterine endometrioid carcinomas; none of 12 uterine serous carcinomas and none of 56 ovarian serous and mucinous carcinomas harbored somatic ARID1A mutations. These findings suggest that the molecular pathogenesis of low-grade uterine endometrioid carcinoma is similar to that of ovarian low-grade endometrioid and clear cell carcinoma, tumors that have previously been shown to have a high-frequency loss of expression and mutation of ARID1A. We further studied the functions of ARID1A and found that restoration of wild-type ARID1A expression in ovarian cancer cells harboring ARID1A mutations suppressed cellular proliferation and tumor growth in mice. Gene silencing of ARID1A in non-transformed epithelial cells enhanced cellular proliferation and tumorigenecity. Mutations in ARID1A and TP53 were mutually exclusive in tumor specimens, and knockdown of ARID1A affected multiple p53-regulated genes and pathways, including CDKN1A and SMAD3. The ARID1A/BRG1 complex bound to the promoters and enhanced transcriptional activity of CDKN1A and SMAD3 in a p53-dependent manner. We further showed that p21 mediated, at least in part, the tumor suppressive functions of ARID1A. These results provide new evidences that ARID1A functions as tissue-type-restricted tumor suppressor by directly modulating transcriptional activity of several p53-regulated genes.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr A45.
Abstract B13: Implication of RNA-binding protein La in proliferation, migration, and invasion of oropharyngeal squamous cell carcinoma cells
Authors: Sommer Gunhild , Rossa Carlos , Chi Angela C. , Neville Brad W. , Heise Tilman 
Published: June 2012

Abstract
The 5-year survival rate for oral cavity cancer is poorer than for breast, colon, or prostate cancer, and has improved only slightly in the last three decades. Hence, new therapeutic strategies are urgently needed. Here, we demonstrate by tissue microarray (TMA) analysis for the first time that RNA-binding protein La is significantly overexpressed in oral squamous cell carcinoma (SCC). We therefore addressed the question whether siRNA-mediated depletion of the La protein may interfere with known tumor-promoting characteristics of head and neck SCC cells. Our studies demonstrate that the La protein promotes cell proliferation, migration, and invasion of lymph node-metastasized hypopharyngeal SCC cells. We also reveal that La is required for the expression of β-catenin as well as matrix metalloproteinase type 2 (MMP-2) within these cells. Taken together, these data suggest a so far unknown function of the RNA-binding protein La in promoting tumor progression of head and neck SCC.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr B13.