bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2583: Regulation of AKT-FoxO signaling by PKG2 inhibits colon cancer cell growth.
Authors: Wang Rui , Kwon In-Kiu , Hu Muhan , Browning Darren D. 
Published: August 2014

Abstract
Signaling through cGMP has emerged as a potentially important suppressor of tumorigenesis in the colon, but the mechanism is poorly defined. Studies of guanylyl-cyclase (GCC) knockout mice indicate that cGMP signaling suppresses proliferation in the colon epithelium, and more recently that inhibition of AKT has an important role. Type-2 cGMP-dependent protein kinase (PKG2) is a central effector of cGMP in the colon epithelium and is a likely mediator of the homeostatic effects of cGMP signaling. The present study sought to determine whether PKG2 can regulate AKT signaling in colon cancer cells and in the colon mucosa. Activation of PKG2 in LS174T and HT29 colon cancer cells inhibited cell proliferation and increased G1 arrest. PKG2 activation also inhibited AKT activity in these cells as determined by immunoblotting for phospho-AKT and downstream phospho-S6. Suggestive of a mechanism, analysis of upstream components revealed that PKG2 increased the levels of phosphatase and tensin homolog (PTEN). Central to the growth-promoting role of AKT signaling is the inactivation of forkhead transcription factors (FoxO), which regulate growth-inhibitory and pro-apoptotic target gene expression. Consistent with the inhibition of AKT signaling, activation of PKG2 significantly increased luciferase reporter activity driven by FoxO-responsive elements in colon cancer cells. This activation was associated with increased levels of several FoxO target genes, including catalase, p27kip. The regulation of AKT/FoxO pathway by PKG2 in vivo was supported by increased phospho-AKT levels, and reduced FoxO target gene expression in the colon mucosa of Prkg2-/- mice compared to wild type siblings. Moreover, activation of cGMP signaling in the colon mucosa led to increased expression of FoxO targets, and suppression of both proliferation and redox stress. Taken together these data define a novel signaling pathway in the colon epithelium, where of PKG2 leads to activation of FoxO. The established tumor suppressor role of the FoxO proteins highlights the potential therapeutic role for cGMP signaling in the prevention of colon cancer.
Citation Format: Rui Wang, In-Kiu Kwon, Muhan Hu, Darren D. Browning. Regulation of AKT-FoxO signaling by PKG2 inhibits colon cancer cell growth. [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 2583. doi:10.1158/1538-7445.AM2013-2583
Abstract 2594: 15-Deoxy-Δ12,14-prostaglandin J2 induces apoptosis through covalent interaction with STAT3: structure-activity relationship and underlying molecular mechanisms.
Authors: Kim Su-Jung , Hahn Young-Il , Choi Bu Young , Suh Young-Ger , Na Hye-Kyung , Surh Young-Joon 
Published: August 2014

Abstract
Our previous studies demonstrated that 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2), a natural ligand for peroxisome proliferator-activated receptor γ, inhibited cell proliferation and induces apoptosis in several cancerous and transformed cell lines. 15d-PGJ2 contains α,β-unsaturated carbonyl groups that can form reversible adducts with thiol nucleophiles. In the present work, we synthesized a series of 15d-PGJ2 analogues by saturating an electrophilic α,β-unsaturated carbonyl moiety in the cyclopentenone ring. Among these, 14,15-dihydro-PGJ2 with a more electrophilic carbon exhibited a potent growth inhibitory activity and induced apoptosis to a greater extent than did 15d-PGJ2. 14,15-Dihydro-PGJ2 as well as 15d-PGJ2 inhibited activation of STAT3, which appeared to be associated with their direct binding to this transcription factor. In contrast, both 9,10-dihydro-15d-PGJ2 and 12,13-14,15-tetrahydro-PGJ2 failed to induce apoptosis and STAT3 activation due to lack of the electrophilic α,β-unsaturated carbonyl moiety. Molecular docking studies suggested that the electrophilic carbon atom of 14,15-dihydro-PGJ2 is placed well in the vicinity of Cys259 of STAT3 to form a covalent Michael adduct. Site-directed mutation of Cys259 of STAT3 abolished its interaction with 15d-PGJ2. 14,15-dihydro-PGJ2 can stably interacted with STAT3, this synthetic cyclopentenone analogue can hence be utilized as a lead compound to develop STAT3 specific inhibitors with anti-tumorigenic activity.
Citation Format: Su-Jung Kim, Young-Il Hahn, Bu Young Choi, Young-Ger Suh, Hye-Kyung Na, Young-Joon Surh. 15-Deoxy-Δ12,14-prostaglandin J2 induces apoptosis through covalent interaction with STAT3: structure-activity relationship and underlying molecular mechanisms. [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 2594. doi:10.1158/1538-7445.AM2013-2594
Abstract 2595: Predictive value tools as an aid in chemopreventive agent development.
Authors: Dunn Barbara K. , Steele Vernon E. , Fagerstrom Richard M. , Topp Carol F. , Ransohoff David , Cunningham Christopher , Lubet Ronald A. , Ford Leslie G. , Kramer Barnett S. 
Published: August 2014

Abstract
Over the past 25 years the Chemoprevention Agent Development Research Group of the Division of Cancer Prevention in the NCI has entered approximately 800 agents into a program designed to test for cancer preventive efficacy. The first 2 key steps in the testing pathway are in vitro/in vitro morphologic assays and, for agents successful in these, anti-tumor testing (tumor incidence and multiplicity reduction) in animal tumor models. Ultimately, agents that successfully decrease tumor incidence and multiplicity in animal models could progress to testing in humans. The goal of the current project is to evaluate the success of our program by determining how accurately the earlier stage assays (morphologic assays) predict efficacy in the later-stage assays (animal tumor assays). In our approach the 208 agents that were tested in both morphologic and animal tumor assays in this program were included in our analysis. Statistical modeling of the input from the 6 most commonly used morphologic assays into predicting the efficacy of agents in animal tumor models was carried out by multimodel inference. The statistical models that were generated predicted the ability of these 6 morphologic assays to predict tumor outcomes in animal models representing (1) all tumor types, (2) breast cancer only, and (3) colon cancer only. The statistical models assigned each morphologic assay a value describing how strongly it predicted outcomes in each of the 3 animal tumor assay settings. The development of these predictive models will guide our future decision-making with respect to agent selection as well as morphologic and animal tumor assay use. Our goal is to improve the efficiency of the overall process of chemoprevention agent development.
Citation Format: Barbara K. Dunn, Vernon E. Steele, Richard M. Fagerstrom, Carol F. Topp, David Ransohoff, Christopher Cunningham, Ronald A. Lubet, Leslie G. Ford, Barnett S. Kramer. Predictive value tools as an aid in chemopreventive agent development. [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 2595. doi:10.1158/1538-7445.AM2013-2595
Abstract 2598: Dietary compounds EGCG and sulforaphane differentially reactivate ER-α in African American and Caucasian breast cancer cells.
Authors: Hardy Tabitha M. , Babatunde Olayode O. , Tollofsbol Trygve O. 
Published: August 2014

Abstract
Breast cancer will affect 1 out of 8 women in their lifetimes and is one of the leading causes of cancer death among women of all races. African American (AA) women, in particular, have a higher breast cancer mortality rate than women of other ethnicities, revealing a clear ethnic disparity. Additionally, AA women tend to have larger, more aggressive tumors and are more likely to be diagnosed with estrogen receptor-α (ER-α)- negative and triple negative breast cancers. While sSocio-economic, cultural and environmental factors are thought to contribute to these disparitiess; however, the extent these aspects play in influencing tumor growth and development is not clearly defined. We sought to address the important question pertaining to the relative contribution of diet in breast cancer disparities and epigenetic modifications. We determined theTo do so we observed the effects of bioactive dietary compounds, (−)-epigallocatechin-3-gallate (EGCG), found in green tea, and sulforaphane (SFN), found cruciferous vegetables such as broccoli sprouts and cauliflower, on breast cancer cells. In order to determine whether ethnicity played a role in these effects breast cancer cells derived from AA and Caucasian (CAU) women that were treated separately or in combination with EGCG and/or SFN. Cell lines were evaluated for cell viability, cellular responses and expression of several genes including ER-α and those associated with epigenetic modifications. We found that AA breast cancer cells displayed distinct variations in response to ECGG and SFN treatments when compared to CAU cell lines. In particular,Specifically, AA-derived cell lines had a delayed ER-α reactivation at a higher dose than did CAU cells. Further, differential expression of several epigenetic modifiers and cancer-related genes was observed in AA cells. These results support the hypothesis that differences variations in gene expression in AA women with breast cancer may be influenced by diet and that innate biological variances based on ethnicity may contribute to these dissimilarities.
Citation Format: Tabitha M. Hardy, Olayode O. Babatunde, Trygve O. Tollofsbol. Dietary compounds EGCG and sulforaphane differentially reactivate ER-α in African American and Caucasian breast 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 2598. doi:10.1158/1538-7445.AM2013-2598
Abstract 260: CD44 isoform specificity in controlling breast tumor initiating cell properties.
Authors: Brown Rhonda L. , Liu Sali , Reinke Lauren M. , Cheng Chonghui 
Published: August 2014

Abstract
Tumor initiating cells (TICs) constitute a small fraction of tumor cells that display stem cell characteristics, including the ability to self-renew and generate heterogeneous tumors. A CD44+/CD24- profile has been widely used to identify TICs in a variety of tumors. However, it has remained unknown whether CD44 is functionally required for TICs and whether a specific CD44 isoform is enriched in TICs. Here, we report that the CD44s isoform is the major splice isoform expressed in a CD44+/CD24- breast stem cell population. Functionally, CD44s is required for expression of a breast stem cell (BSC) gene signature and is essential for mammosphere formation. Modulation of CD44 alternative splicing by the splicing regulator ESRP1 prevents CD44s production and, in turn, inhibits mammosphere formation and expression of the BSC signature. Furthermore, CD44s is required for limiting numbers of TICs to form tumors in an animal model of breast cancer progression. Together, these data illustrate that the CD44s splice isoform is enriched in CD44+/CD24- breast stem cells and serves as an important regulator of stem cell properties. Our results also suggest that CD44s-dependent TIC properties can be controlled at the level of alternative splicing by splicing factors that regulate production of specific CD44 isoforms.
Citation Format: Rhonda L. Brown, Sali Liu, Lauren M. Reinke, Chonghui Cheng. CD44 isoform specificity in controlling breast tumor initiating cell properties. [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 260. doi:10.1158/1538-7445.AM2013-260
Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
Abstract 2604: Involvement of circulating fibrocytes in the progression of adenocarcinomas by modulating EMT and tumor microenvironment.
Authors: Asafova Alina , Nikam Vandana , Schmall Anja , Seeger Werner , Voswinckel Robert , Savai Rajkumar 
Published: August 2014

Abstract
Background: Circulating fibrocytes (CFs) are bone marrow derived, mesenchymal progenitor cells that have emerging role in many diseases. CFs was shown to participate in tissue remodeling in pulmonary hypertension and fibrosis, via secretion of different cytokines and growth factors. Nevertheless, their role in the lung cancer still has to be delineated. Thus, our aim is to identify the role of CFs in lung cancer progression and metastatic potential.
Results/methods: We generated CFs by isolating human peripheral blood mononuclear cells (PBMCs) and culturing them for 10 days until they differentiated into CFs. Purity (≥95%) of the CFs population was analyzed by flow cytometry and immunofluorescence. Co-culturing of A549 (human alveolar adenocarcinoma cells) and CFs for 12 and 24 hrs, followed by collection of conditioned medium (CM) and RNA from both cells yielded interesting results. Co-cultured CM promoted proliferation (1.31±0.07 versus 1.5±0.13) and migrating capacity (64.6±26.5 versus 472.8±103.4) of A549 tumor cells. In addition, co-cultured CM caused epithelial-to-mesenchymal transition (EMT) of A549 cells; epithelial markers (E-cadherin, cytokeratin) were downregulated, and mesenchymal markers (α-smooth muscle actin, fibronectin) were upregulated.
In vivo to study the CFs involvement in lung cancer, we co-injected CFs with A549 cells or A549 cells alone and measured the tumor growth after 28 days. The tumor size was significantly increased (1354.8±333.6 versus 3042.4±373.4) in co-injected group (CF+A549) compared to A549 alone. Screening for genes regulated in co-injected group tumors showed regulation of tumor microenvironment, an increase in macrophage markers (CSF1R, CD68, CD200, MMD), angiogenesis markers (EDNRB, THBS1) and ECM remodeling markers (MMP14, CTSB, CTSH) compared to A549 tumor alone.
Conclusions: We believe that circulating fibrocytes may play positive role in the tumor growth and progression. The increase in EMT and migration, may suggest their involvement in invasion and metastasis. Targeting CFs and their secretory molecules can be of therapeutic importance in lung cancer.
Citation Format: Alina Asafova, Vandana Nikam, Anja Schmall, Werner Seeger, Robert Voswinckel, Rajkumar Savai. Involvement of circulating fibrocytes in the progression of adenocarcinomas by modulating EMT and tumor microenvironment. [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 2604. doi:10.1158/1538-7445.AM2013-2604
Abstract 2617: uPAR and cathepsin B knockdown-induced nuclear translocation of JNK inhibits migration and induces apoptosis in glioma-initiating cells.
Authors: Alapati Kiranmai , Kesanakurti Divya , Rao Jasti S. 
Published: August 2014

Abstract
Treatment for glioblastoma (GBM) remains essentially palliative due to the aggressive infiltration of GBM cancer cells into normal brain tissue. In addition, the existence of a small subpopulation of highly resistant cells known as glioma-initiating cells (GICs), which escape radiation and chemotherapy-induced cell death, makes GBM currently incurable. Proteases, such as uPAR and cathepsin B that are responsible for cancer invasion and metastasis, are often detected in higher amounts in malignant tumors. In the present study, shRNA-mediated knockdown of uPAR and cathepsin B (pUC), alone or in combination with radiation, simultaneously inhibited migration and induced apoptosis of 5310 and 4910 non-GICs and GICs by regulating the JNK-MAPK pathway. Immunoblot and immunocytochemical analyses showed pUC treatment resulted in an increase in the levels of the phospho-JNK (p-JNK), which was mostly localized to the nucleus. We also observed an increase in the levels of p-JNK with radiation and with full-length uPAR and cathepsin B; however, it was confined to the cytoplasm of the cells. Depletion of cytosolic p-JNK with pUC treatment and/or with the JNK inhibitor decreased migration by downregulating the expression of the migratory molecules. Immunoprecipitation analysis and co-localization studies further confirmed the involvement of the cytosolic p-JNK in promoting migration of the glioma cells. The increase in the expression of nuclear p-JNK with pUC treatment increased the expression of apoptotic molecules, as observed by the western blot analysis. MTT assay revealed that non-GICs and GICs were rescued from pUC-induced cell death when treated in combination with a JNK inhibitor, which further confirms the importance of nuclear JNK in eliciting an apoptotic signal. In summary, cytosolic p-JNK aids cell migration while nuclear p-JNK drives cells toward cell death. As such, pUC treatment induced the translocation of p-JNK from cytoplasm to the nucleus, thereby simultaneously inhibiting migration and inducing apoptosis of non-GICs and GICs.
Citation Format: Kiranmai Alapati, Divya Kesanakurti, Jasti S. Rao. uPAR and cathepsin B knockdown-induced nuclear translocation of JNK inhibits migration and induces apoptosis in glioma-initiating 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 2617. doi:10.1158/1538-7445.AM2013-2617
Abstract 2619: Whole genome and transcriptome sequencing identifies an activating mutation of LPAR1 in a patient with metastatic neuroblastoma.
Authors: Wei Jun S. , Johansson Peter , Chen Li , Song Young K. , Tolman Catherine , Li Samuel , Hurd Laura , Patidar Rajesh , Wen Xinyu , Badgett Thomas C. , Cheuk Adam , Marshall Jean-Claude , Steeg Patricia , Vaqué Díez José Pedro , Gutkind J Silvio , Khan Javed 
Published: August 2014

Abstract
Neuroblastoma is the most common extra-cranial solid tumor of childhood, and is one of the most genomically heterogeneous malignances studied to date. Despite advance of multimodal therapies, the current overall survival rate for patient with metastatic neuroblastoma is &lt;40%, and the molecular events that drive the disease are not fully understood. To systematically identify expressed driver oncogenes, we performed whole genome and transcriptome sequencing on an index liver metastasis of neuroblastoma from a young adult patient. Additional transcriptome sequencing was performed on tumor cells from bone marrow taken at diagnosis and from the adrenal primary taken at the time of primary surgical resection. Whole genome sequencing of the index tumor identified 44 somatic small variant mutations in 42 genes and a large hemizygous deletion in the ATRX gene which has been recently implicated in neuroblastoma. Of these 45 somatic alterations, 15 genes including ATRX were found commonly mutated in all three tumors and transcriptome sequencing showed 3 of them (LPAR1, GATA2, and NUFIP1) had high level of expression of the mutant alleles, suggesting potential oncogenic driver roles for these mutated genes. Among these commonly mutated expressed genes, the druggable G-protein coupled receptor LPAR1 was expressed at the highest level in all tumors. Cells expressing the LPAR1 mutant resulted in a significant increase in motility, but had no effect on growth. Further biochemical characterization demonstrated that elevated Rho signaling was responsible for the increased cell mobility mediated by the LPAR1 mutant. Therefore, parallel whole genome and transcriptome sequencing identified a cell motility driver mutation in the LPAR1 gene, and this combinatorial approach may be leveraged for identification of expressed driver mutations in cancer patients for precision therapy.
Citation Format: Jun S. Wei, Peter Johansson, Li Chen, Young K. Song, Catherine Tolman, Samuel Li, Laura Hurd, Rajesh Patidar, Xinyu Wen, Thomas C. Badgett, Adam Cheuk, Jean-Claude Marshall, Patricia Steeg, José Pedro Vaqué Díez, J Silvio Gutkind, Javed Khan. Whole genome and transcriptome sequencing identifies an activating mutation of LPAR1 in a patient with metastatic neuroblastoma. [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 2619. doi:10.1158/1538-7445.AM2013-2619
Abstract 263: Identification of subgroup of triple negative breast cancer by cancer stem cell markers.
Authors: Kida Kumiko , Ishikawa Takashi , Yamada Akimitsu , Shimada Kazuhiro , Narui Kazutaka , Sugae Sadatoshi , Shimizu Daisuke , Tanabe Mikiko , Sasaki Takeshi , Ichikawa Yasushi , Endo Itaru 
Published: August 2014

Abstract
[Background]
Anti-cancer agents are essential for treating triple negative breast cancer (TNBC). The cases resistant to them showed unfavorable clinical courses and thus may require novel agents. It is crucial to predict the efficacy of existing agents in TNBC. Recently, cancer stem cell (CSC) theory has drawn an attention in relation to TNBC and chemoresistance. Aldehyde dehydrogenase 1 (ALDH1) is a biomarker of breast cancer stem cell.
[Aims]
In order to subdivide TNBC and finally find subgroup resistant to existing anti-cancer agents and better markers for stem cell phenotype.
[Methods]
1)The expression of ALDH1 was examined immunohistochemically in each subtype of 447 breast cancer patients.
2)The expression of ALDH1 and its association with Ki-67,P53, CK5/6 or EGFR were examined in TNBC.
3)Correlation between ALDH1 and pathological response by neoadjuvant chemotherapy was examined.
4)ALDH1 positive and negative cells were collected by microdissection from 5 ALDH1 positive breast cancer cases. The expression profile was assessed by Affymetrix cDNA microarray. The difference of profile between ALDH-1 positive and negative cells was assessed.
[Results]
1)The expression rate of ALDH1 was 4.5% in Luminal type, 11.1% in Luminal-HER2 type, 23.8% in HER2-enriched type and 33.6% in triple negative type. ALDH1 was expressed highly in TNBC.
2)In 79 TNBC with neoadjuvant chemotherapy, 29 cases(36.7%) was positive for ALDH1.The averages of NG, Ki67 and p53 were 2.7, 37.8% and 37.7% respectively in ALDH1 positive TNBC. 80% of them were positive for CK5/6 or EGFR. There was no significant correlation between ALDH1 and these pathological markers.
3) Poorly responsiveness to NAC (0-1b) was found in 17 cases (21.5%). Only ALDH1 was associated with chemoresistance to NAC (P=0.033), suggesting ALDH1 positive TNBC were resistant to anticancer agents.
4)63 and 41 genes were up- and down-regulated respectively in ALDH1 positive cells. These potential related genes are now under investigation.
[Conclusions]
ALDH1 could be a marker for chemoresistance in TNBC. As ALDH1 identifies some specific subpopulation of breast cancer, further studies will provide important information on subdividing TNBC and individualizing treatment of this intractable subtype.
Citation Format: Kumiko Kida, Takashi Ishikawa, Akimitsu Yamada, Kazuhiro Shimada, Kazutaka Narui, Sadatoshi Sugae, Daisuke Shimizu, Mikiko Tanabe, Takeshi Sasaki, Yasushi Ichikawa, Itaru Endo. Identification of subgroup of triple negative breast cancer by cancer stem cell markers. [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 263. doi:10.1158/1538-7445.AM2013-263