bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract LB-150: Role of EGFR signaling in an inducible mouse model of astrocytomas
Authors: Song Yurong , Zhang Qian , Miller C. Ryan , Threadgill David , McCarthy Ken D. , Van Dyke Terry 
Published: February 2011

Abstract
No effective therapy currently exists for astrocytomas, particularly the most biologically aggressive subtype, glioblastoma multiforme (GBM). Recently, The Cancer Genome Atlas (TCGA) project reported the most extensive genetic analysis of GBMs enhancing our ability to query altered signaling pathways potentially involved. Yet, an understanding of disease etiology requires extensive modeling in mammalian genetic systems coupled with analyses of biological contributions of disease. Here we genetically perturbed the primary molecular pathways (pRb and Ras) reported by TCGA in genetically engineered mouse models (GEM). Alterations were induced specifically in adult GEM astrocytes via a tamoxifen-inducible, human GFAP promoter-driven CreERTM allele. GEM with astrocyte RB pathway inactivation alone (T) developed low-grade astrocytomas (grade II). Constitutive KRAS activation alone (R) did not produce detectable brain pathology. GEM harboring both inactivated RB and constitutively active KRAS (TR) in astrocytes developed high-grade astrocytomas (grade III) with low frequency of GBM development (grade IV). EGFR level and its ligands in TR tumors were elevated compared to T alone, suggesting EGFR signaling pathway may play an important role in tumor progression. We reasoned that tumor progression would be delayed if we knocked out EGFR in TR brain. Surprisingly, we found that addition of EGFR inactivation produced tumors with higher frequency of GBM. These results suggest other pathways other than EGFR may compensate for EGFR loss, which in turn contributes to tumor progression. These highly penetrant, inducible GEM models provide a unique system for delineating the downstream pathways and resulting biological abnormalities critical to astrocytoma pathogenesis and for preclinical drug and biomarker development. Initial studies have begun to define the relative contribution to disease of each disrupted pathway, including potential targets for therapeutic intervention.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-150.
Abstract LB-152: Characterization of the first mouse model of anaplastic thyroid carcinoma
Authors: Dima Mariavittoria , Cristofano Antonio Di 
Published: February 2011

Abstract
Although anaplastic thyroid carcinoma is a rather uncommon malignancy, it accounts for the vast majority of deaths from thyroid cancer. Despite considerable efforts, its dismal prognosis has not changed in decades. Building on the increasing knowledge of the molecular events involved in anaplastic carcinoma pathogenesis, we have generated a mouse model in which the Pten and p53 tumor suppressor genes have been selectively deleted in the thyroid follicular cells. By six months of age, double mutant mice develop undifferentiated, aggressive thyroid carcinomas arising, like in most human patients, from pre-existing follicular carcinomas. These tumors are invariably locally invasive, and often metastasize to the lungs. Similar to their human counterpart, they display loss of expression of most thyroid differentiation and functional markers, including Thyroid peroxidase (Tpo), Thyroglobulin (Tg), and the therapeutically relevant Sodium-iodide symporter (Nis). A combined approach, using both double mutant mice and several stable cell lines derived from tumors that developed in these mutants, is uncovering the molecular pathways involved in the transformation and dedifferentiation process, as well as pointing to novel potential targets for therapeutic intervention.
In conclusion, this compound mouse mutant represents a unique, clinically relevant model of thyroid anaplastic carcinoma, and an invaluable tool for both basic and preclinical studies.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-152.
Abstract LB-155: Molecular targeted therapy of stem cell leukemia-lymphoma induced by ZNF198-FGFR1
Authors: Ren Mingqiang , Cowell John K. 
Published: February 2011

Abstract
Chimeric ZNF198-FGFR1 tyrosine kinase induces patients developing stem cell leukemia-lymphoma syndrome (SCLL), a novel hematological malignancy characterized by rapid transformation to acute myeloid leukemia and T-lymphoblastic lymphoma. Current therapy is inadequate. Using array comparative genomic hybridization (aCGH) we have previously demonstrated that a loss of TCR is a crucial event that perturbed the final maturation stages of T cell development and induced double positive T-lymphoma formation. However, TCR knockout mice did not show T-cell lymphoma development, which indicates that deletion of TCR is unsufficient to induce T-lymphoblastic lymphoma formation. Here we demonstrate that the constitutive activation of Notch1 is frequently seen in the lymphoma from ZNF198-FGFR1 transduced and transplanted mice, in consistent with high expression of the majority of known downstream targets of Notch1. Using ZNF112 cells, a newly derived cell lines from one disease mouse bone marrow, as a model system we found that both DAPT (a γ-secretase inhibitor to block Notch signaling) and transcriptional knockdown of either Notch1 or its co-activator MAML1 via shRNA in ZNF112 cells can significantly delay or prevent the leukemogenesis in syngeneic transplanted mice. These data demonstrate the importance of Notch signaling in the etiology of this disease and provide an important clinical implication that tyrosine kinase inhibitors plus drugs inhibiting Notch signaling can be a promising strategy to treat SCLL patients.
This work was supported by grant CA076167 from the National Institutes of Health.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-155.
Abstract LB-16: Altered circadian rhythm components are resynchronized by melatonin in human prostate cancer
Authors: Jung Brittney D. , Huang Wei , Ahmad Nihal 
Published: February 2011

Abstract
Prostate cancer (PCa) is a major age-related malignancy as increasing age correlates with increased risk for developing this neoplasm. Similarly, alterations in circadian rhythms, because of modifications in various core clock components, have also been associated with the aging population and cancer risk. The pineal hormone melatonin is known to regulate circadian rhythm, which is under the control of a core set of genes: Per-, Clock- and Bmal-family members. The circulating serum levels of melatonin have been shown to decrease in patients with cancer including PCa. Interestingly, melatonin has been shown to have anti-proliferative effects in certain cancers. We have recently found that melatonin imparts anti-proliferative effects in vitro and in vivo via inhibiting Sirt1 that is a class III histone deacetylase and involved in the regulation of aging and several other metabolic processed. In this study, we challenged the hypothesis that melatonin imparts anti-proliferative effects in prostate cancer via resynchronization of deregulated core clock circuitry at the cellular level. First, we determined if the core clock genes circuitry is disrupted in PCa. Interestingly, we found that Clock and Per2 protein levels were downregulated whereas Bmal1 protein levels were up regulated in PCa cells (LNCaP, 22R 1, DU145, PC3), compared to normal prostate epithelial cells as assessed by Western blot analysis. Further, we employed the automated quantitative analysis (AQUA) system to asses the levels of Clock, Per2 and Bmal1 in a tissue microarray (TMA) containing clinical specimens of benign prostate hyperplasia (BPH), high-grade intraepithelial neoplasias (HGPIN), localized PCa, aggressive PCa with metastases as well as benign prostate tissue. We found that compared to benign tissues, in all proliferative prostate diseases Clock and Per2 levels were downregulated whereas Bmal1 levels were up regulated. In addition, a forced over-expression of Per2 was found to result in a significant loss of viability of PCa cells. Further, we found that melatonin (1mM and 2mM; 48 h) treatment causes an increase in Per2 and Clock and decrease in Bmal1 (at the protein and mRNA levels) in human PCa cells. Furthermore, as shown by the COSOPT algorithm, we found that melatonin treatment resulted in a resynchronization of oscillatory circadian rhythm genes (Dbp and Per2) while having no effect on non-oscillatory genes. Our data support our hypothesis and suggest that melatonin should be thoroughly investigated as an agent for the management of PCa and other age-related malignancies.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-16.
Abstract LB-163: Genetic and pharmaceutical approaches for the study of complement factors as alternative therapy for ovarian cancer
Authors: Nunez-Cruz Selene , Qu Hongchang , Rafail Stavros , Connolly Denise , Gimotti Phyllis , Lambris John , Coukos George , Scholler Nathalie 
Published: February 2011

Abstract
Chronic inflammation is now clearly established as a key player in the process of carcinogenesis. Complement factors can be activated under various chronic inflammatory conditions, suggesting that they could contribute in promoting tumor development. However, the role of complement in ovarian cancer (OC) progression remains poorly investigated. OC is the second most common gynecologic cancer and the fourth leading cause of cancer death in women. Developing alternative therapies is required to decrease OC high mortality rate. To determine the role of complement in cancer establishment and progression, we used genetic and pharmaceutical approaches. We first crossed complement component 3 knockout (C3KO) mice with transgenic mice expressing the Simian Virus 40 TAg under the control of the Müllerian Inhibiting Substance type II Receptor promoter (Tg-MISIIR-TAg). Tg-MISIIR-TAg mice develop bilateral OC resembling human serous OC with ∼100% penetrance. We found that C3KO/MISIIR-TAg mice developed no or very small tumors at 16 weeks of age compared to control wild-type C3/MISIIR-TAg and C3/MISIIR-TAg heterozygote littermates. We also found that tumor-infiltrating leukocytes were functionally altered with changes of secretion profiles for cytokines and angiogenic factors. Second, we orthotopically implanted fluorescent ovarian carcinoma cells (MOV1Kat) in Tg-MISIIR-TAg mice treated with complement C5aR inhibitor peptide or control peptide. MOV1 cell line was isolated from Tg-MISIIR-Tag tumor and transducted with a Far-red fluorescent protein, Katushka, using TurboFP635 Lentivirus mammalian vector to permit in vivo optical imaging (IVIS). Our results showed that the pharmacological inhibition of C5a-binding to C5aR receptor promoted tumor regression.
Altogether, our results indicated an important and understudied role of complement for ovarian cancer. We propose that complement inhibitors could be used as therapeutic agents for the treatment of ovarian cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-163.
Abstract LB-165: Novel metabolic metyltransferase mediates radiation resistance in glioblastomas
Authors: Palanichamy Kamalakannan , Gordon Nicolaus , Patel Disha , Shirai Katsuyuki , Chakravarti Arnab 
Published: February 2011

Abstract
Purpose: Nicotinamide-N-methyltransferase(NNMT) is an enzyme involved in the metabolism of drugs and xenobiotic compounds. It is known to be highly expressed in a variety of cancers and has been investigated for its potential use as a diagnostic or prognostic marker. Furthermore, clinical data has shown that high NNMT expression is correlated with adverse patient outcome. In our glioblastoma (GBM) patient data set and other publically available data set NNMT is one among the top 25 genes which is differentially regulated when compared with normal adjacent tissue and also with various grades of brain tumor. NNMT is highly expressed in grade IV compared to low grade astrocytomas. Kaplan-Meier survival plots for NNMT gene shows that higher expression is associated with poor survival benefit and the median survival was found to be more than doubled in patient group with low expression of NNMT. Despite all this, the mechanistic behavior of NNMT in the malignant phenotype remains uncharacterized. We plan to gain an understanding of the signaling pathways with which NNMT interacts and elucidate its role in radioresistance.
Experimental Design: The in vitro radiosensitivity assays were evaluated using wild type, NNMT-knockdown and NNMT-overexpression GBM cell lines. The assay conducted includes MTS, DNA damage and repair, Clonogenic survival assay, comet assay, Annexin V apoptosis assay, matrigel invasion assays, ATP assay, etc. The cell line after treatment was lysed and probed for pro-and anti-survival signaling pathways.
Results and Discussion: We explored the expression profile of NNMT in established (ATCC) and in our panel of primary GBM cell lines. The expression levels correlates with relative radioresistance exhibited by the cell line. It appears NNMT knockdown cell lines exhibited an enhanced radiosensitivity. Currently we are probing signaling cascades which are differentially regulated in the NNMT knockdown and overexpression cell lines and also the differential response to radiation treatment based on differing levels of NNMT expression. The results will be presented at the meeting.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-165.
Abstract LB-167: Identification of ionizing radiation (IR)-responsive mRNA in p53-deficient human non-small cell lung cancer (NSCLC) grown in three-dimensional cell culture system
Authors: Kwon Jee Young , Kim Jong Suk , Seo Young Rok 
Published: February 2011

Abstract
Non-small cell lung cancer (NSCLC) has been known as the most common human malignancy. The p53 tumor suppressor gene is mutated in approximately 50 % of NSCLC. For treatment of lung cancer, radiotherapy using -ray is general treatment. However, many patients suffer from recurred disease. Therefore, the definite mechanism of radiation based on in vivo mimic system is required for effective remedical value to NSCLC. Most of radiation biology studies were performed in conventional monolayer culture system which can not represent in vivo tumor environment. Hence, study applying in vivo mimic three-dimensional culture system is necessary to elucidate the molecular mechanism of solid tumor. Here, we analyzed gene expression profile induced by ionizing radiation (IR) in H1299 cells grown as spheroid in three-dimensional cell culture system. Our data showed that different gene expression profiles among monolayer culture system, three-dimensional small spheroid and three-dimensional large spheroid system. Particularly, genes related with microenvironment including adhesion junction and hypoxia had different expression level in three-dimensional spheroid system compare with monolayer culture system. This study suggested that in vivo mimic three-dimensional cell culture engineering approach might provide critical clues for understanding of cellular responses in p53 mutated or deleted lung cancer cells against IR. (* This work was supported by Nuclear Research Development Program of the Korea Science and Engineering Foundation (KOSEF) grant funded by the Korean government (MEST). (Grand code: 2007-2001431, 2008-2001694, 2009-0078295) from Korea Science and Engineering Foundation)
Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-167.
Abstract LB-169: Sulfasalazine sensitizes glioblastoma cells to radiation treatment
Authors: Sleire Linda , Wang Jian , Heggdal Jan , Pedersen Paal-Henning , Enger Per Øyvind 
Published: February 2011

Abstract
Glioblastomas (GBMs) are lethal cancers with a limited response to ionizing radiation. Recent studies suggest that Sulfasalazine (SAS), a drug used to treat inflammatory bowel disease, inhibits the xCT antiporter system in glioma cells, thereby blocking their uptake of cystine. Since the availability of cystine is a rate limiting step in intracellular antioxidant production, we wanted to investigate whether sulfasalazine sensitizes glioma cells to radiation. SAS effect on glioma cell growth was investigated using a electric cell substrate impedance sensing (ECIS) instrument. All cell lines showed altered growth curves in response to SAS treatment. Further, U251 glioma cells were treated with escalating doses of SAS, alone or in combination with radiation (8 Gy). Immunocytochemistry for the apoptotic marker Annexin V as well as DAPI staining to assess nuclear integrity were conducted to estimate cell death following treatment.
All treatment groups exhibited increased rates of cell death compared to untreated controls. However, a combination of SAS and radiation resulted in higher levels of cell death, than radiation or SAS administered alone. In order to assess whether this can be exploited therapeutically, we are currently preparing to treat nude rats harbouring gliblastoma biopsy xenografts with SAS, alone or in combination with radiation.
Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-169.
Abstract LB-174: Use of massively parallel, next-generation sequencing to identify gene mutations beyond ERAS that predict response to panitumumab in a randomized, phase 3, monotherapy study of metastatic colorectal cancer (mCRC)
Authors: Peeters Marc , Oliner Kelly S. , Parker Alex , Huang Jing , Siena Salvatore , Humblet Yves , Van Laethem Jean-Luc , André Thierry , Wiezorek Jeffrey , Reese David , Patterson Scott D. , Van Cutsem Eric 
Published: February 2011

Abstract
Discussant: Sabine Tejpar, Kuleuven Center for Human Genetics, Leuven, Belgium.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-174.
Abstract LB-176: Discovery of CWP232291: A novel and potent small molecule inhibitor of Wnt signaling in hematological malignacies
Authors: Cha Joo Young , Jung Ji-Eun , Emami Kathy , Briaud Isabelle , Tenzin Fnu , Pyon Younghee , Lee Donghee , Chung Jae Uk , Lee Jong Heun , Oh Se-Woong , Jung Kyung Yun , Pai Jin Keon 
Published: February 2011

Abstract
Discussion
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-176.
Abstract LB-177: New temozolomide analogs with activity independent of mismatch repair and alkyltransferase
Authors: Wheelhouse Richard T. , Pletsas Dimitrios , Li Li , Garelnabi Elrashied A.E. , Phillips Roger M. 
Published: February 2011

Abstract
Discussion
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-177.
Abstract LB-185: Decreased LINE-1 methylation in peripheral blood is associated with breast cancer risk in the Sister Study
Authors: Bolick Sophia CE. , Xu Zongli , DeRoo Lisa , Sandler Dale P. , Taylor Jack A. 
Published: February 2011

Abstract
Discussion
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-185.
Abstract LB-186: Genetic variants and risk of lung cancer in never-smokers: A genome-wide association study
Authors: Li Yafei , Sheu Chau-Chyun , Ye Yuanqing , de Andrade Mariza , Wang Liang , Chang Shen-Chih , Aubry Marie-Christine , Aakre Jeremiah , Allen Mark , Chen Feng , Cunningham Julie , Deschamps Claude , Jiang Ruoxiang , Lin Jie , Marks Randolph , Pankratz V. Shane , Su Li , Li Yan , Sun Zhifu , Tang Hui , Vasmatzis George , Wang Renyi , Harris Curtis , Spitz Margaret , Jen Jin , Zhang Zuo-Feng , Christiani David , Wu Xifeng , Yang Ping 
Published: February 2011

Abstract
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-186.
Abstract LB-188: Positive regulation of the Ras oncogene by ubiquitination
Authors: Sasaki Atsuo T. , Cantley Lewis C. 
Published: February 2011

Abstract
Discussion
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-188.