bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5264: Negative regulation of AMPK-dependent metabolic-stress pathways by MIF and D-DT in non-small cell lung carcinoma.
Authors: Brock Stephanie , Rendon Beatriz , Yaddanapudi Kavitha , Mitchell Robert 
Published: August 2014

Abstract
AMP-activated protein kinase (AMPK) is a nutrient and metabolic stress sensing enzyme activated by the tumor suppressor kinase, LKB1. Because macrophage migration inhibitory factor (MIF) and its functional homolog, D-dopachrome tautomerase (D-DT), have pro-tumorigenic functions in non-small cell lung carcinoma (NSCLC) but have AMPK activating properties in nonmalignant cell types, we set out to investigate this apparent paradox. Our data now suggest that, in contrast to MIF and D-DT's AMPK activating properties in non-transformed cells, MIF and D-DT cooperatively act to inhibit steady state phosphorylation and activation of AMPK in LKB1 wildtype and LKB1 mutant human NSCLC cell lines. Our data further indicate that MIF and D-DT - acting through their shared cell surface receptor, CD74 - antagonize NSCLC AMPK activation by maintaining glucose uptake, ATP production and redox balance resulting in reduced Ca2+/calmodulin-dependent kinase kinase [[Unsupported Character - Symbol Font &#946;]] (CaMKK[[Unsupported Character - Symbol Font &#946;]])-dependent AMPK activation. Combined, these studies indicate that MIF and D-DT cooperate to inhibit AMPK activation in an LKB1-independent manner. This suggests that MIF and D-DT promote a unique and well conserved adaptation pathway that is usurped by the malignant cells in order to counter metabolic stress-induced, AMPK-dependent, tumor suppression. Importantly, because the LKB1 tumor suppressor locus is mutated in over 30% of NSCLC lesions rendering these tumors insensitive to AMPK-dependent growth suppression, the identification of unique AMPK agonists would be expected to have a tremendous impact on NSCLC disease management for clinicians. Taken together, simultaneous therapeutic targeting of both MIF and D-DT represents an innovative and clinically efficacious approach to re-activating metabolic stress-induced tumor suppression in NSCLC malignant lesions.
Citation Format: Stephanie Brock, Beatriz Rendon, Kavitha Yaddanapudi, Robert Mitchell. Negative regulation of AMPK-dependent metabolic-stress pathways by MIF and D-DT in non-small cell lung carcinoma. [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 5264. doi:10.1158/1538-7445.AM2013-5264
Abstract 5278: Circulating microRNAs profile as a novel biomarker for osteosarcoma.
Authors: Allen-Rhoades Wendy , Kurenbekova Lyazat , Hilsenbeck Susan , Man Tsz-Kwong , Donehower Lawrence , Yustein Jason T. 
Published: August 2014

Abstract
Osteosarcoma (OS) is the primary bone tumor in children, with approximately 400 cases each year diagnosed in patients under the age of twenty. Current therapies can achieve long-term relapse free survival rates near 75% for those with localized disease, while survival rates for patients with overt metastatic disease at diagnosis are often less than 20%. Without adjuvant chemotherapy, over 80% of children will develop metastatic or recurrent disease and all patients require long term monitoring. However, there are no reliable, non-invasive biological markers to detect the presence or progression of disease, assess therapy response, or provide upfront risk stratification. The present method for detecting and monitoring disease status in OS is radiographic imaging which is often difficult to interpret. MicroRNAs (miRNAs) are evolutionarily conserved, stable, small non-coding RNA molecules that are key post-transcriptional regulators and are ideal candidates for circulating biomarker development due to their stability in plasma, ease of isolation with high sensitivity, and the unique expressions associated with specific disease states. As such, we have developed a signature profile of circulating miRNAs utilizing a novel genetically engineered mouse model of OS that can discriminate between mice with and without OS. Specifically, we have determined that circulating miR-205 is decreased 3.2-fold in mice with disease compared to disease-free mice, whereas miR-574-3p, miR-214, and miR-335-5p are increased 1.4, 1.9, and 2.9 fold respectively in the diseased mice. Finally, based upon prior studies utilizing other cancer models, we believe that we will be able to directly translate these findings from the mouse model to patients afflicted with osteosarcoma.
Citation Format: Wendy Allen-Rhoades, Lyazat Kurenbekova, Susan Hilsenbeck, Tsz-Kwong Man, Lawrence Donehower, Jason T. Yustein. Circulating microRNAs profile as a novel biomarker for osteosarcoma. [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 5278. doi:10.1158/1538-7445.AM2013-5278
Abstract 528: Characterization of Δ7/11, a functional prolactin-binding protein.
Authors: Fleming Jodie M. , Ginsburg Erika , McAndrew Christopher , Heger Christopher , Cheston LaShanda , Rodriguez-Canales Jaime , Vonderhaar Barbara K. , Paul Goldsmith 
Published: August 2014

Abstract
Prolactin is essential for normal mammary gland development and differentiation, and has been shown to promote tumor cell proliferation and chemotherapeutic resistance. Soluble isoforms of the prolactin receptor have been reported to regulate prolactin bioavailability by functioning as “prolactin binding proteins.” Included in this category is Δ7/11, a product of alternate splicing of the prolactin receptor primary transcript. However, the direct interactions of prolactin with Δ7/11, and the resulting effect on cell behavior, have not been investigated. Herein, we demonstrate the ability of Δ7/11 to bind prolactin using a novel proximity ligation assay and traditional immunoprecipitation techniques. Biochemical analyses demonstrated that Δ7/11 was heavily glycosylated, similar to the extracellular domain of the primary prolactin receptor, and that glycosylation regulated the cellular localization and secretion of Δ7/11. Low levels of Δ7/11 were detected in serum samples of healthy volunteers, but were undetectable in human milk samples. Expression of Δ7/11 was also detected in six of the 62 primary breast tumor biopsies analyzed; however, no correlation was found with Δ7/11 expression and tumor histotype or other patient demographics. Functional analysis demonstrated the ability of Δ7/11 to inhibit prolactin-induced cell proliferation as well as alter prolactin-induced rescue of cell cycle arrest/early senescence events in breast epithelial cells. Collectively, these data demonstrate that Δ7/11 is a novel regulatory mechanism of prolactin bioavailability and signaling.
Citation Format: Jodie M. Fleming, Erika Ginsburg, Christopher McAndrew, Christopher Heger, LaShanda Cheston, Jaime Rodriguez-Canales, Barbara K. Vonderhaar, Goldsmith Paul. Characterization of Δ7/11, a functional prolactin-binding protein. [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 528. doi:10.1158/1538-7445.AM2013-528
Abstract 5290: MicroRNA-495-3p functions as tumor suppressor by targeting multiple oncogenic epigenetic effector molecules in gastric cancer.
Authors: Kim Min Gyu , Kim Seung Jin , Bae Hyun Jin , Noh Ji Heon , Kim Jeong Kyu , Eun Jung Woo , Jung Kwang Hwa , Chang Young Gyoon , Shen Qingyu , Park Won Sang , Lee Jung Young , Nam Suk Woo 
Published: August 2014

Abstract
Epigenetic effector molecules are involved in many biological processes by regulating post-translational histone modification and DNA methylation. Recent evidence has suggested that several epigenetic effectors are aberrantly over-expressed in gastric cancer (GC). However, underlying regulatory mechanisms of those molecules are not completely understood. In this study, we identified miR-495-3p which regulates multiple epigenetic effectors through a comprehensive miRNA profiling analysis with in silico target prediction in GC. The down-regulation of miR-495-3p was demonstrated in a subset of GC tissue, revealing inverse correlation with expression levels of epigenetic effectors that were predicted to be targeted by miR-495-3p. Ectopic overexpression of miR-495-3p in GC cells suppressed protein expression and 3’-UTR (untranslated region) reporter luciferase activity of multiple epigenetic effectors including histone deacetylase 2 (HDAC2), SET and MYND domain-containing protein 3 (SMYD3), DNA methyltransferase 1 (DNMT1) and metastasis-associated protein1 (MTA1). Moreover, miR-495-3p attenuated cancer cell proliferation accompanied with LC3B-II conversion, PARP cleavage, p16INK4A expression and down-regulation of CDK4/6 and cyclin D1, which were implicated in autophagic cell death, apoptosis and cell cycle regulation, respectively. In addition, ectopically over-expressed miR-495-3p inhibits cell migration via suppressing epithelial-mesenchymal transition (EMT)-related molecules, Snail and SLUG. Taken together, we suggest that a loss or down-regulation of endogenous miR-495-3p triggers aberrant overexpression of multiple oncogenic epigenetic effector molecules, and thereby miR-495-3p functions as a tumor suppressor in gastric tumorigenesis.
Citation Format: Min Gyu Kim, Seung Jin Kim, Hyun Jin Bae, Ji Heon Noh, Jeong Kyu Kim, Jung Woo Eun, Kwang Hwa Jung, Young Gyoon Chang, Qingyu Shen, Won Sang Park, Jung Young Lee, Suk Woo Nam. MicroRNA-495-3p functions as tumor suppressor by targeting multiple oncogenic epigenetic effector molecules in gastric 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 5290. doi:10.1158/1538-7445.AM2013-5290
Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
Abstract 5297: The caHUB biospecimen pre-analytical variables program.
Authors: Carithers Latarsha , Vaught Jim 
Published: August 2014

Abstract
The Cancer Human Biobank is an infrastructure that the Biorepositories and Biospecimen Research Branch of the Cancer Diagnosis Program at NCI uses to carry out highly specialized tissue collections to support biospecimen research programs. Specifically, the caHUB Biospecimen Pre-analytical Variables Program collects data on how variables in tissue collection, handling, storing and shipping standard operating procedures affect downstream analysis. Phase one of this program will assess variations in formalin fixation procedures. This will include examining the effects of (i) time delay to the start of tissue fixation after resection and (ii) overall tissue formalin fixation time on the signal of key proteomic markers used for diagnostic treatment that will be assessed by immunohistochemistry. Future phases of this study will address a variety of pre-analytical variables and alternate analysis platforms. The results of this project will be used to determine best practices for molecular preservation and lead to the development of evidence-based protocols for optimal collection, processing, and storage of biospecimens.
Citation Format: Latarsha Carithers, Jim Vaught. The caHUB biospecimen pre-analytical variables program. [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 5297. doi:10.1158/1538-7445.AM2013-5297
Abstract 530: Inhibition of amphiregulin-mediated EGFR signaling suppresses tumorigenicity in breast cancer cells.
Authors: Kappler Christiana S. , Ethier Stephen P. 
Published: August 2014

Abstract
Approximately half of all basal type breast cancers show evidence of autocrine activation of the epidermal growth factor receptor (EGFR) by amphiregulin (AREG). In addition, AREG expression is associated with aggressive and chemoresistant forms of breast cancer. Studies in our laboratory show that when AREG is the activating ligand, EGFR accumulates at the cell surface, resulting in altered receptor trafficking and downstream signaling. To investigate the effect of AREG-mediated activation of EGFR on the phenotype of AREG-expressing cancers, AREG expression was knocked-down in SUM149 cells, a highly tumorigenic and metastatic cell line isolated from a basal subtype inflammatory breast cancer, which expresses high levels of AREG and overexpresses EGFR. Microarray analysis of AREG knockdown cells revealed a number of relevant pathways affected by AREG-EGFR signaling. These pathways include Notch signaling, MAPK activation, IL-1 signaling and multiple components of the Wnt signaling pathway. In particular, knockdown of AREG or inhibition of EGFR signaling in AREG stimulated cells resulted in the upregulation of DKK-1, an antagonist of canonical Wnt signaling, and the expression of several WNT target genes. Flow cytometric analysis of these cells demonstrated that AREG knockdown resulted in a significant reduction in CD44+ cells while simultaneously increasing the non-stem cell fraction of CD44-/CD24+ cells. Because CD44hi/CD24lo is characteristic of undifferentiated cells that have the potential to initiate tumor formation, the tumorigenicity of these cells was investigated by transplanting parental and AREG knock-down SUM149 cells into the mammary fat pads of NOD-SCID mice. The tumorigenic activity of the AREG knock-down derivatives was significantly reduced compared to the parental SUM149 cells. In particular, the AREG knockdown clone that expressed the lowest level of AREG expression and the highest level of DKK-1 expression failed to form tumors in NOD-SCID mice. To investigate the link between AREG-mediated activation of EGFR, receptor trafficking, and downstream signaling pathways that are responsible for changes in expression of WNT pathway genes, we are investigating differences in EGFR phosphorylation and downstream signaling stimulated by AREG versus EGF. In conjunction with our previous findings that AREG-mediated EGFR signaling results in activation of NF-κβ and the upregulation of IL1α/β, our current results suggest a link between these pathways, WNT signaling, and tumorigenicity in SUM-149 cells.
Citation Format: Christiana S. Kappler, Stephen P. Ethier. Inhibition of amphiregulin-mediated EGFR signaling suppresses tumorigenicity in 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 530. doi:10.1158/1538-7445.AM2013-530
Abstract 5309: Characterization of a novel oncogene SPOCK1 in humanhepatocellular carcinoma.
Authors: Guan Xin-Yuan , Li Yan , Chen Leilei , Yuan Yun-Fei 
Published: August 2014

Abstract
CHD1L is as an
SNF-2-like transcription factor involved in development of hepatocellular carcinoma (HCC) and SPOCK1 is one of the genes upregulated by CHD1L. In this study, we found that overexpression of SPOCK1 could be detected in 92/135 (68%) of HCCs, which was significantly associated with advanced clinical stage (P=0.020) and metastasis (P=0.024). A significantly positive correlation (Pearson correlation coefficient 0.619, P&lt;0.001) between the expressions of CHD1L and SPOCK1 was detected by qRT-PCR in this cohort of HCC specimens. ChIP-PCR assay confirmed that CHD1L protein bound directly to the promoter region (nt-1662 to +34) of SPOCK1 and activated transcription. Levels of SPOCK1 mRNA were increased among tumors that became metastatic, compared with those that did not, and among patients with shorter overall and disease-free survival times. Ectopic expression of SPOCK1 in HCC cells increased proliferation, foci formation, and colony formation in soft agar; these cells also formed larger xenograft tumors, more rapidly, in nude mice than control
HCC cells. Silencing SPOCK1 expression with short hairpin RNA had the opposite effects. We found that SPOCK1 prevents apoptosis of HCC cells by activating Akt, to block release of cytochrome c and activation of caspases -9 and -3; these effects were reversed with an Akt inhibitor. HCC cells that overexpressed SPOCK1 expressed higher levels of MMP9, were more invasive in Matrigel assays, and formed more metastatic nodules in immunodeficient mice than control HCC cells.
In conclusion, CHD1L activates expression of SPOCK1, which activates Akt signaling to block apoptosis and invasion by HCC cells, in culture and in mice. Levels of SPOCK1 increase with progression of human HCC. SPOCK1 might be used as a prognostic factor or therapeutic target.
Citation Format: Xin-Yuan Guan, Yan Li, Leilei Chen, Yun-Fei Yuan. Characterization of a novel oncogene SPOCK1 in humanhepatocellular carcinoma. [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 5309. doi:10.1158/1538-7445.AM2013-5309
Abstract 5312: Mutational analysis of the tyrosine kinome in serous and clear cell endometrial cancers.
Authors: Rudd Meghan L. , Mohamed Hassan , Price Jessica C. , Urick Mary Ellen , O'Hara Andrea J. , Gallo Matthieu Le ,   NISC Comparative Sequencing Program, Cruz Pedro , Zhang Suiyuan , Mullikin James , Merino Maria J. , Bell Daphne W. 
Published: August 2014

Abstract
Endometrial cancers (ECs) arise from the inner epithelial lining of the uterus. At diagnosis, the majority of ECs are carcinomas of endometrioid, serous, or clear cell histologies, or an admixture of at least two of these histological subtypes. Serous and clear ECs are rare at presentation but contribute disproportionately to mortality from EC. Thus, there is an acute need for novel therapeutic approaches to treat serous and clear cell ECs. Small molecule inhibitors directed against tyrosine kinases have shown clinical efficacy in other types of cancer in which the target kinase is mutationally activated. Here, we used Sanger sequencing to systematically search for somatic mutations within 527 exons that encode the catalytic domains of 85 tyrosine kinases from 23 serous, 10 clear cell, and 5 mixed histology ECs. For mutated genes, we extended the screen to another 73 ECs (21 serous, 10 clear cell, 42 endometrioid). Genes that were mutated in both the primary and secondary screens were resequenced in a tertiary screen to search for mutations in all coding exons among the entire panel of 111 endometrial tumors. Overall, we uncovered nonsynonymous somatic mutations of ACK1, DDR1, and KDR in 5.4%, 3.6%, and 1% of ECs. Serous tumors had mutated ACK1, DDR1 and KDR in 2.3%, 4.5%, and 2.3% of cases. Clear cell tumors had mutated ACK1 in 5% of cases. Endometrioid tumors had mutated DDR1 in 2.3% of cases. Immunoblotting confirmed that ACK1 and DDR1 are endogenously expressed in endometrial cancer cell-lines. Eighty-seven percent (7 of 8) of ACK1 mutations and 50% (2 of 4) of DDR1 mutations are predicted to impact protein function. To our knowledge this is the first report of ACK1 and DDR1 mutations in endometrial cancer. Our findings warrant future studies to determine whether the ACK1 and DDR1 mutations uncovered here are pathogenic.
Citation Format: Meghan L. Rudd, Hassan Mohamed, Jessica C. Price, Mary Ellen Urick, Andrea J. O'Hara, Matthieu Le Gallo, NISC Comparative Sequencing Program, Pedro Cruz, Suiyuan Zhang, James Mullikin, Maria J. Merino, Daphne W. Bell. Mutational analysis of the tyrosine kinome in serous and clear cell endometrial 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 5312. doi:10.1158/1538-7445.AM2013-5312
Abstract 5335: miR-31 contributes to immortalization and epithelial-mesenchymal transition of oral keratinocyte.
Authors: Tu Hsi-Feng , Hung Pei-Shi , Liu Chung-Ji , Lin Shu-Chuin , Chang Kuo-Wei 
Published: August 2014

Abstract
Oral squamous cell carcinoma (OSCC) is a prevalent malignancy worldwide. MicroRNAs (miRNAs) are short, non-coding RNAs that regulate gene expression by RNA interference and crucial for tumorigenesis. Our previous studies identified miR-31 as an oncogenic miRNA of OSCC, and the increased miR-31 may be contributive to oral carcinogenic process in the early stages. This study further specified the higher miR-31 expression in dysplastic potential malignant disorder (PMD) tissues than non-dysplastic PMD tissues in oral cavity. In addition, miR-31 in the patient's saliva was significantly higher than control subjects. To elucidate the contribution of miR-31 in modulating the extended growth of normal oral keratinocyte, exogenous expression of both miR-31 and hTERT genes were introduced to normal oral keratinocyte (NOK) culture, which led to immortalization of two NOK lines, designated M31OK1 and M31OK3. These immortalized lines exhibited cellular phenotypes lying between NOKs and OSCC cell lines and diminished expression of senescence-associated β-galactosidase. Knockdown of hTERT and/or miR-31 decreased the growth and migration of both lines. M31OK1 also carries p53 gene mutation in codon 273, exhibiting the tolerance to serum-induced senescence, anchorage-independent growth and epithelial-mesenchymal transition (EMT) properties relative to NOK. However, the stemness properties were not increased in M31OK1 in relation to NOKs. Knockdown of miR-31 expression decreased the expression of vimentin and ZEB1 and slightly increased E-cadherin expression in M31OK1 cells. This was correlated with the clinical findings that high miR-31 expression was associated with higher expression of VEGF and lower expression of E-cadherin in PMD tissues. This study concluded that miR-31 may be contributive to early oral carcinogenesis by stimulating factors to facilitate cellular immortalization or by modulating the expression of EMT markers in oral keratinocytes.
Citation Format: Hsi-Feng Tu, Pei-Shi Hung, Chung-Ji Liu, Shu-Chuin Lin, Kuo-Wei Chang. miR-31 contributes to immortalization and epithelial-mesenchymal transition of oral keratinocyte. [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 5335. doi:10.1158/1538-7445.AM2013-5335