bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1269: Activation of the NKG2D receptor differentially activates mTOR and NFκB signaling pathways in CD8+ T cells.
Authors: Barber Amorette E. , Bedsworth Taylor , Spence Jasmine , Whitman Emily 
Published: August 2014

Abstract
To induce strong anti-tumor immune responses, CD8+ T cells require stimulation through the TCR and costimulatory receptors. Each costimulatory molecule can have a unique effect on the function of T cells due to differential activation of downstream signaling pathways and gene expression. One costimulation molecule that is likely to be engaged in the tumor microenvironment is NKG2D since the ligands for this receptor are expressed in over 80% of tumors. In order to determine how activation of costimulatory receptors in the tumor microenvironment affects CD8+ T cell functions, previous studies have compared the activation of CD8+ T cells through CD3 in combination with either CD28 or NKG2D and showed that CD3 and NKG2D stimulated cells secreted less anti-inflammatory cytokines. Both costimulatory receptors activated AKT, however the altered cytokine secretion was due to the unique activation of β-catenin in NKG2D stimulated cells. This study aimed to further investigate the differences in the signaling pathways downstream of AKT that are activated by CD3 /CD28 and CD3/NKG2D. Specifically, this study focused on the activation of mammalian target of rapamycin complex 1 and 2 (mTORC1 and mTORC2) along with nuclear factor kappa B (NFκB), all of which have been shown to have important roles in the CD8+ T cell anti-tumor functions. Activation of the mTORC1, mTORC2 and NFκB pathways were compared in murine CD8+ effector T cells stimulated through CD3 alone, CD3 and CD28 or CD3 and NKG2D. The activation of mTORC1was measured through phosphorylation of its downstream effectors including 4-EBP1, P70SK6 and HIF-1, while mTORC2 measured activation of AKT, SGK1 and NFkβ. Activation of CD8+ T cells through CD3 and NKG2D decreased activation of mTORC1 while increasing activation of mTORC2. Together this shows that activation through NKG2D leads to the differential activation of signaling pathways, thus likely altering the anti-tumor effector functions of the CD8+ T cells.
Citation Format: Amorette E. Barber, Taylor Bedsworth, Jasmine Spence, Emily Whitman. Activation of the NKG2D receptor differentially activates mTOR and NFκB signaling pathways in CD8+ T cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1269. doi:10.1158/1538-7445.AM2013-1269
Abstract 1274: SLITRK6, the target of a novel antibody drug conjugate AGS15E, is expressed in bladder and other cancers.
Authors: YANG Peng , Coleman Jeffrey , Li Ying , Zhang Yi , Junge Candice , Morrison Kendall , Donate Fernando , Stover David , Morrison Karen 
Published: August 2014

Abstract
SLITRK6, a member of the SLITRK family of neuronal transmembrane proteins, was discovered by Agensys using suppressive subtractive hybridization on biopsies from bladder cancer patients. Immunohistochemical (IHC) analysis of SLITRK6 expression was evaluated in various human cancers including bladder, using a SLITRK6-specific antibody M15-68(2)22. This mouse monoclonal antibody was raised to a peptide contained within the extracellular domain of SLITRK6 and was selected as a suitable IHC reagent by screening on RNA positive and negative cell lines and xenografts. Subsequent analysis of SLITRK6 expression in human cancer tissue microarray samples, utilizing M15-68(2)22, showed positive staining in 90% of 452 cases of bladder transitional cell carcinoma, including in situ, advanced primary and metastatic tumors. A subset of lung primary and metastatic cancers, breast cancers and glioblastomas also expressed SLITRK6. In normal tissues SLTRK6 expression is highly restricted to limited epithelia, including transitional epithelium, and some mast cells. In view of the restricted expression in normal tissues and the high expression in bladder transitional cell carcinoma, SLITRK6 constitutes an excellent target for antibody drug conjugate therapy for bladder transitional cell carcinoma and, potentially, for other cancer indications.
Citation Format: Peng YANG, Jeffrey Coleman, Ying Li, Yi Zhang, Candice Junge, Kendall Morrison, Fernando Donate, David Stover, Karen Morrison. SLITRK6, the target of a novel antibody drug conjugate AGS15E, is expressed in bladder and other cancers. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1274. doi:10.1158/1538-7445.AM2013-1274
Abstract 1291: Identification of penfluridol as potential treatment for pancreatic cancer cells.
Authors: Chien Wenwen , Lee Kian Leong , Sun Qiaoyang , Wuensche Peer , Sudo Makoto , Poellinger Lorenz , Tyner Jeffrey W. , Yang Henry , Koeffler H. Phillip 
Published: August 2014

Abstract
Tyrosine kinase inhibitors (TKIs) have provided promising anti-cancer activities, but intrinsic or acquired resistance to these drugs is a major problem. To overcome this resistance, we have used microarray analysis to identify a signature of intrinsic drug resistance in human pancreatic cancer cells, and applied this gene expression profile to silico drug screening for potential drugs for pancreatic cancer therapy. The potency of dasatinib (a multiple family TKI) was assessed against a panel of 14 human pancreatic cancer cell lines. This drug is undergoing clinical trials for pancreatic cancers. Nine of fourteen pancreatic cell lines were growth inhibited by dasatinib. Three dasatinib-resistant (MiaPaCa2, Panc1, SU8686) and three -sensitive (Panc0504, Panc1005, Panc0403) pancreatic cancer cell lines were used in microarray analysis to compare the gene expression profiles. A total of 598 genes were differentially expressed in dasatinib-resistant cell lines compared to the sensitive cell lines. To discover therapeutic drugs that sensitize pancreatic cancer cells to dasatinib, we performed in silico drug screening using the Connectivity Map database (CMAP). The gene signature induced by thioridazine in CMAP showed a “glove in hand” pattern to that found in dasatinib-resistant versus -sensitive pancreatic cancer cell lines. Thioridazine belongs to the phenothiazine family including chlorpromazine, perphenazine, penfluridol, and pimethixene. Each was examined. Assays of cell proliferaton, cell cycle, and Annexin V showed that each was effective at inhibiting the cell cycle and inducing apoptosis. Penfluridol (a calcium channel inhibitor) was the most potent against both the dasatinib-resistant and -sensitive pancreatic cancer cell lines. Drug combination studies of penfluridol and either dasatinib or gemcitabine (FDA-approved for pancreatic cancer) showed synergistic enhancement of cytotoxicity. Mechanistic investigations suggested that multiple signaling pathways were suppressed by penfluridol. These studies suggest a potential novel class of drugs for treatment of pancreatic cancers.
Citation Format: Wenwen Chien, Kian Leong Lee, Qiaoyang Sun, Peer Wuensche, Makoto Sudo, Lorenz Poellinger, Jeffrey W. Tyner, Henry Yang, H. Phillip Koeffler. Identification of penfluridol as potential treatment for pancreatic cancer cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1291. doi:10.1158/1538-7445.AM2013-1291
Abstract 1299: KEAP1-NRF2-ARE signaling interacts with the SWI/SNF chromatin remodeling complex in non-small cell lung cancer.
Authors: Song Shujie , Orvis Tess , Zheng Yanfang , Major Michael B. , Weissman Bernard E. 
Published: August 2014

Abstract
NF-E2-related factor 2 (NRF2), negatively regulated by KEAP1, modulates induction of a battery of cytoprotective genes against oxidative stress via binding to the antioxidant responsive element (ARE) sequence. Recent NGS studies have shown a significant number of mutations in the KEAP1-NRF2-ARE signaling pathway, implicating aberrant activation of this pathway in lung cancer carcinogenesis and chemoresistance. The SWI/SNF chromatin-remodeling complex, employing either
BRG1 or BRM as a catalytic subunit, regulates gene expression and alters chromatin structures in an ATP-dependent manner. Loss of complex function often occurs in lung cancers, via mutations in complex subunits. Since KEAP1/NRF2 mutations and BRG1/BRM loss occur frequently in non-small cell lung cancers (NSCLCs) in a mutually exclusive fashion, we hypothesized that BRG1 and/or BRM play(s) a role in the regulation of NRF2 target genes. To test this hypothesis, we developed a series of isogenic H358 NSCLC lines with reduced BRG1 and/or BRM expression using shRNA technology. We observed a significant increase in the levels of HMOX1 (heme oxygenase1) and GSTM4 (Glutathione
S-transferase Mu 4) with a concomitant decrease in NQO1 (NAD(P)H dehydrogenase, quinone 1) in the BRG1-deficient H358 cell lines. However, GCLM (Glutamate–cysteine ligase regulatory subunit) was elevated only in the BRM-reduced H358 cells. Interestingly, BRG1 loss, either alone or combined with BRM loss, promoted SDS-resistant KEAP1 dimerization. We are currently examining whether BRG1 and/or BRM loss increases ROS levels. Chromatin immunoprecipitation (ChIP) showed that NRF2 were enriched at NRF2 downstream genes in both H358 parental and vector control cells, whereas BRG1 knockdown led to a moderate increase (HMOX1) or decrease (NQO1) in NRF2 binding. These results provide evidence that loss of
SWI/SNF chromatin remodeling complex activity alters the NRF2 pathway in NSCLC.
Furthermore, novel drugs targeting NRF2 downstream genes might provide a therapeutic approach for BRG1 deficient NSCLC patients.
Citation Format: Shujie Song, Tess Orvis, Yanfang Zheng, Michael B. Major, Bernard E. Weissman. KEAP1-NRF2-ARE signaling interacts with the SWI/SNF chromatin remodeling complex in non-small cell lung cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1299. doi:10.1158/1538-7445.AM2013-1299
Abstract 1309: ERβ1 induces apoptosis in lung cancer cells by regulating growth factor signaling.
Authors: Thomas Christoforos , Nikolos Fotis , Rajapaksa Gayani , Bado Igor , Gustafsson Jan-Ake 
Published: August 2014

Abstract
Estrogens have recently been associated with the clinical outcome of patients with non-small cell lung cancer (NSCLC). The wild-type estrogen receptor β (ERβ1) one of the mediators of the estrogen signaling in cells is expressed in lung cancer. However, the role of ERβ1 in NSCLC cell growth has not been fully elucidated. Here we show that induction of ERβ1 expression inhibited cell growth in H1299 and A549 NSCLC cells. Treatment of these cells with the ERβ agonists 17β-estradiol or 3β-Adiol further decreased cell proliferation and induced apoptosis. ERβ1 was found to induce apoptosis through stimulation of the intrinsic apoptotic pathway that involves upregulation of the proapoptotic protein Bim. Inactivation of the extracellular-signal-regulated kinases ERK1/2 was found to be involved in the ERβ1-mediated induction of apoptosis since treatment with EGF that activates ERK1/2 abolished the ability of ERβ1 to sustain the apoptotic phenotype. These results suggest that, by regulating NSCLC cell growth, ERβ1 could be an important factor in biology of lung cancer and a potentially useful component in the clinical management of the disease.
Citation Format: Christoforos Thomas, Fotis Nikolos, Gayani Rajapaksa, Igor Bado, Jan-Ake Gustafsson. ERβ1 induces apoptosis in lung cancer cells by regulating growth factor signaling. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1309. doi:10.1158/1538-7445.AM2013-1309
Abstract 1324: PMEPA1 enhances the prostate cancer cell growth inhibitory effect of MDV3100 and bicalutamide.
Authors: Li Hua E. , Heidenberg Daniel , Dobi Albert , Srivastava Shiv 
Published: August 2014

Abstract
Introduction and Objective: PMEPA1 is a highly androgen-inducible gene in prostate cancer cells, recruits the NEDD4-1, an E3 ubiquitin ligase, to degrade AR. We hypothesize that the frequently (65%) observed decrease or loss of PMPEA1 expression in human prostate tumors may lead to enhanced AR functions and accelerated prostate tumorigenesis. Therefore, we investigated the growth and survival of prostate cancer cells in the presence of AR inhibitors in response to PMEPA1 knockdown.
Methods: PMEPA1 was silenced by PMEPA1 Mission shRNA lentivirus infection and puromycin selection in LNCaP and VCaP cells respectively. The PMEPA1 deficient LNCaP and VCaP cells were treated with the AR inhibitors (MDV3100 and bicalutamide), as well as the artificial synthesized androgen R1881. Ectopic NEDD4-1 was expressed by pCMV-XL4-NEDD4-1 eukaryotic expression vector. Cell growth was monitored by cell counting assay, BrdU incorporation assay and colony plating efficiency assay. Cell cycle was analyzed with propidium iodide staining based flowcytometry assay. Protein levels of AR, PMEPA1, PSA and NEDD4-1 were assessed by immunoblot assays.
Results: PMEPA1 silenced LNCaP and VCaP cells had higher AR, PSA protein levels, suggesting activated AR signaling. Consistent with this observation, inhibition of PMEPA1-1 by shRNA resulted in increased cell growth, stronger BrdU incorporation ability and higher colony plating efficiency in both LNCaP and VCaP cells. Cell cycle assay showed more S-phase cells in PMEPA1 deficient LNCaP and VCaP cells in regular medium or R1881 supplemented charcoal-striped medium. Ectopic expression of NEDD4-1 could not inhibit cell growth in PMEPA1 silenced LNCaP cells. More interestingly, the PMEPA1 deficient CaP cells (both LNCaP and VCaP cells) demonstrated more resistance to the growth inhibitory effects of MDV3100 and bicalutamide.
Conclusions: The frequently observed decreased expression of PMEPA1 results in elevated AR protein levels and activated AR signaling, which in turn promotes cell growth in androgen responsive prostate cancer cells. The PMEPA1 deficient cells develop more resistance to AR inhibitors. Our findings further suggest the important role of decreased PMEPA1 in AR related prostate tumorigenesis. These data highlight that PMEPA1 deficiency may confer resistance to AR inhibitors during CaP progression.
This study is supported by the NIH grant (R01CA106653) to SS.
Citation Format: Hua E. Li, Daniel Heidenberg, Albert Dobi, Shiv Srivastava. PMEPA1 enhances the prostate cancer cell growth inhibitory effect of MDV3100 and bicalutamide. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1324. doi:10.1158/1538-7445.AM2013-1324
Abstract 1335: Association between polymorphisms of APE1 and OGG1 genes and risk of colorectal cancer in Taiwan.
Authors: Yeh Chih-Ching , Hsieh Ling-Ling , Tang Reiping 
Published: August 2014

Abstract
Background: Colorectal cancer (CRC) is the third leading cause of cancer death in Taiwan. Previous studies indicated that oxidative damages resulting from reactive oxygen species (ROS) generation participate in all stages of the cancer process. Mutagenic 8-hydroxy-2’-deoxyguanosine, one of the major DNA lesions generated by ROS, is preferentially repaired by 8-oxoguanine glycosylase I (OGG1) and apurinic-apyrimidinic endonuclease 1 (APE1). Since polymorphisms of OGG1 S326C, R154H and APE1 D148E, T-656G were associated with the enzyme activities, this study was designed to evaluate the roles of the OGG1 and APE1 polymorphisms in CRC risk.
Method: We recruited 727 newly diagnosed colorectal adenocarcinoma cases and 736 age- and sex-matched healthy controls in a medical center. Genomic DNA isolated from buffy coat was used for genotyping by PCR methods. Because the frequency of the sequence variants of OGG1 R154H was too low (H allele was 0.14%), this polymorphism was excluded in further data analysis. Unconditional logistic regressions were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs).
Results: Subjects with OGG1 326 Ser/Cys genotype had an increased CRC risk (OR = 1.47; 95% CI = 1.06-2.04) compared to those carrying the Ser/Ser genotype, particularly among individuals aged more than 60 years (OR = 1.60, 95% CI = 1.02-2.05). However, there was no significant association between APE1 polymorphisms and CRC risk.
Conclusion: Our results indicated that OGG1 S326C polymorphism may associate with CRC risk in Taiwanese population, whereas APE1 polymorphisms may not modulate this disease risk.
Citation Format: Chih-Ching Yeh, Ling-Ling Hsieh, Reiping Tang. Association between polymorphisms of APE1 and OGG1 genes and risk of colorectal cancer in Taiwan. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1335. doi:10.1158/1538-7445.AM2013-1335
Abstract 134: Smoking duration before first childbirth: An emerging risk factor for breast cancer? Results from the Norwegian National Health Service Cohort (NHHS).
Authors: Bjerkaas Eivind , Parajuli Ranjan , Engeland Anders , Mascarinec Gertraud , Selmer Randi , Weiderpass Elisabete , Gram Inger Torhild 
Published: August 2014

Abstract
Purpose - Recent studies suggest that the period before the first childbirth is important in the relation between smoking and risk of breast cancer. We wanted to examine this association with focus on smoking duration before the first childbirth.
Methods - We followed 302,865 Norwegian women born between 1899 -1975 and identified 7,490 cases of primary invasive breast cancer cases during &gt; 4.1 million person years of observation (mean 14 person years). We used Cox proportional hazard models to find hazard ratios (HR) with 95 % confidence intervals (CIs) adjusting for age, education, parity, age at first childbirth, BMI and physical activity. Information came from a questionnaire and a physical examination at enrolment, and from linkages to national registries.
Results - Compared with women who had never smoked, current smokers had a 14% [HR= 1.14 (95% CI 1.08-1.20)] and former smokers a 17% [HR=1.17 (95% CI 1.10-1.24)] increased risk of breast cancer. Ever smokers who started to smoke after their first childbirth did not have an increased risk [HR=0.93 (95% CI 0.86-1.02)], compared with never smokers. Those who had smoked for more than 20 years, and who had smoked 11 or more of those years before the first childbirth, showed a doubling in risk [HR=1.97 (95% CI 1.33-2.93)] compared with those starting to smoke after the first childbirth.
Conclusions - Our study suggests that duration of smoking before the first childbirth is a key factor in the relationship between smoking and breast cancer.
Citation Format: Eivind Bjerkaas, Ranjan Parajuli, Anders Engeland, Gertraud Mascarinec, Randi Selmer, Elisabete Weiderpass, Inger Torhild Gram. Smoking duration before first childbirth: An emerging risk factor for breast cancer? Results from the Norwegian National Health Service Cohort (NHHS). [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 134. doi:10.1158/1538-7445.AM2013-134
Abstract 1347: CXCR4 pathway associated with family history of melanoma.
Authors: LI Wenqing , Han Jiali , Widlund Hans , Correll Mick , Wang Yaoyu , Quackenbush John , Mihm Martin , Laga Canales Alvaro , Golub Todd , Hoshida Yujin , Hunter David , Murphy George , Kupper Thomas , Qureshi Abrar 
Published: August 2014

Abstract
Background & Aims: Inherited genetic variants involved in the etiology of melanoma predispose towards elevated risk of disease, but known allele variants only account for a limited fraction of family history-associated melanoma cases. Hence, there is a need to determine contributing allele variants associated with augmented risk and surrogate biomarkers, which can be used to discern family history-associated melanoma.
Methods: Using data from the Nurses’ Health Study cohort, family history was defined as having one or more immediate family members diagnosed with melanoma. Secondary confirmation of melanoma cases were reviewed by pathology reports and tumor blocks collected by mail from across the United States. Genomic interrogation was accomplished through evaluating formalin-fixed paraffin-embedded tissues from 78 primary cutaneous invasive melanoma cases, using expression profiling on either a 6K or whole-genome (24K) Illumina gene chip. Gene Set Enrichment Analysis was performed separately for each batch to determine the differentially enriched pathways and key contributing genes.
Results: The CXC chemokine receptor 4 (CXCR4) pathway was consistently up-regulated within cases of familial melanoma in both platforms. Leading edge analysis showed four genes from the CXCR4 pathway, including MAPK1, PLCG1, CRK, and PTK2, were among the core members that contributed to the enrichment of this pathway. There was no association between the enrichment of CXCR4 pathway and NRAS, BRAF status, or Breslow thickness of the primary melanoma cases.
Conclusion: We found that the CXCR4 pathway may constitute a novel susceptibility pathway associated with family history of melanoma in first-degree relatives.
Citation Format: Wenqing LI, Jiali Han, Hans Widlund, Mick Correll, Yaoyu Wang, John Quackenbush, Martin Mihm, Alvaro Laga Canales, Todd Golub, Yujin Hoshida, David Hunter, George Murphy, Thomas Kupper, Abrar Qureshi. CXCR4 pathway associated with family history of melanoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1347. doi:10.1158/1538-7445.AM2013-1347