bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4618: Elucidating the role of distinct glutaminase isoforms in cancer.
Authors: Liu Bonnie , Song Kyung , Kwong Mandy , Gao Min , Hong Rebecca , Nannini Michelle , Sampath Deepak , Belvin Marcia , Peterson David , Evangelista Marie , Daemen Anneleen , Firestein Ron , Hatzivassiliou Georgia 
Published: August 2014

Abstract
Glutaminase is a key enzyme for the conversion of glutamine to glutamate with subsequent use as a fuel in the TCA cycle, glutathione production and protein synthesis. A subset of tumor cells shows preferential dependency on glutamine and glutaminase for cell proliferation and survival, consistent with “metabolic addiction” to this pathway. Between two glutaminase loci in the genome, the gene for kidney-type glutaminase (Gls1) has 2 alternatively spliced products (KGA and GAC), with distinct regulation and expression from liver-type glutaminase (Gls2). Furthermore, based on distinct C-termini and enzymatic properties, it has been proposed that the Gls1 alternatively spliced isoforms (KGA and GAC) may themselves have distinct functions. Our data further elucidates the role of glutaminase in cancer by addressing the following key questions: a) what is the major role of glutaminase in cells most sensitive to its inhibition? b) is GAC interchangeable with KGA in its expression pattern and role in tumor cells? c) how do tumors adapt to glutaminase inhibition? By generating and using a panel of GAC and KGA isoform-selective reagents we show that the two isoforms have distinct patterns of expression and distinct roles in cell proliferation, migration and tumor growth in vivo. In addition, based on metabolomics, functional and complementation assays, we propose a mechanistic basis for tumor cell dependency on glutaminase and the tumor adaptive response to glutaminase inhibition. Our data reveal the basis for the addiction of tumor subsets to glutaminase and elucidate the role of distinct isoforms of kidney-type glutaminase isoforms in cancer.
Citation Format: Bonnie Liu, Kyung Song, Mandy Kwong, Min Gao, Rebecca Hong, Michelle Nannini, Deepak Sampath, Marcia Belvin, David Peterson, Marie Evangelista, Anneleen Daemen, Ron Firestein, Georgia Hatzivassiliou. Elucidating the role of distinct glutaminase isoforms in 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 4618. doi:10.1158/1538-7445.AM2013-4618
Abstract 4652: Proteomic profiling of platinum based anticancer drugs.
Authors: Dzubak Petr , Ozdian Tomas , Holub Dusan , Rylova Gabriela , Rehulka Jiri , kollareddy Madhusudhan , Mlcuchova Daniela , Hajduch Marian 
Published: August 2014

Abstract
Carboplatin, cisplatin and oxaliplatin are structurally similar anticancer drugs and their mechanism of action is permanent coordination to DNA and interfering with DNA repair. However, these drugs have different anticancer activities in human tumors, adverse effects and dose limiting toxicities. Therefore, we performed complex proteomic profiling in order to characterize cellular effects of all three platinum based anticancer drugs. To identify the molecular basis of different pharmacological properties, expressional characteristics of cells exposed to vincristine and daunorubicin were used in parallel as prototypes of drugs with different mechanism of action. T-lymphoblastic leukemia CCRF-CEM cells were treated with 5x IC50 concentrations of individual drugs for time equivalent to half-time to induction apoptosis. Untreated (control) cells were cultured with heavy amino acid labeled media in order to enable relative quantification of peptide expression using SILAC technology, LC-MS/MS and LC-MALDI-TOF/TOF. Results were processed by Proteinscape software equipped by Mascot and Phenyx analytical algorithms. We identified 646 ± 133 proteins by ESI and 312 ± 85 proteins by MALDI in average of all fifteen replicates. Identified results were further processed by in-house written script to remove outlier peptides and to normalize individual runs. All replicates were summed, and statistic analysis was done. To see up- and down- regulated proteins, the hierarchical clustering and PCA analysis was performed. Hierarchical clustering revealed that cisplatin and carboplatin shares the same cluster what is conclusive with literature. Surprisingly, the cluster of daunorubicin and vincristine was close to cisplatin and carboplatin and the oxaliplatin was in the separated cluster from rest of four drugs. PCA analysis revealed 30 proteins with contribution higher than 1 %. The highest contribution (7.5 %) to drug clustering have proteins involved in DNA remodeling. These proteins could be used as specific biomarkers of therapy by platinum based compounds.
Citation Format: Petr Dzubak, Tomas Ozdian, Dusan Holub, Gabriela Rylova, Jiri Rehulka, Madhusudhan kollareddy, Daniela Mlcuchova, Marian Hajduch. Proteomic profiling of platinum based anticancer drugs. [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 4652. doi:10.1158/1538-7445.AM2013-4652
Abstract 4849: An association between genetic variant in Epidermal Growth Factor (EGF) gene and survival benefit from epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in never smokers with advanced adenocarcinoma of the lung.
Authors: Lee Youngjoo , Yoon Kyong-Ah , Lee Jin Soo 
Published: August 2014

Abstract
Background
EGFR mutations are strong predictors for efficacy to EGFR-TKIs in non-small cell lung cancer (NSCLC). However, it is unknown whether inherited genetic variants can influence the EGFR-TKI efficacy in patients harboring EGFR mutations.
Methods
We genotyped 271,817 single-nucleotide polymorphisms (SNP) in 348 advanced NSCLC patients who received chemotherapy. Seventeen top survival-related SNPs were identified using cut-off minimum P-value of &lt;5.0 x 10−5 in at least 70% of 1000 bootstrap samples. Among the 17 genes, we focused on whether SNPs in the EGF gene have predictive value for survival benefit from EGFR-TKIs in 215 never smokers with advanced adenocarcinoma of the lung, which were selected as EGFR mutation-enriched patients, receiving EGFR-TKI treatment during the disease course.
Results
The survival benefit by treatment with EGFR-TKIs was different between patients with common and variant genotypes of rs11098063 at the 4q25: EGF gene [hazard ratio (HR) of ever to never use of EGFR-TKIs, 0.72 (95% CI, 0.42-1.22) in CC genotype vs. 0.27 (95% CI, 0.15-0.50) in CT/TT genotype; interaction of SNP*EGFR-TKIs, P = 0.075] in Cox proportional hazard regression model adjusted for known prognostic factors. In the CT/TT group (n= 89), there was a significant improvement in survival with EGFR-TKIs [never vs. ever use of EGFR-TKIs; median overall survival (OS), 16 (95% CI, 12-21) vs. 37 (95% CI, 31-42) months; log-rank test, P &lt; 0.001]. However, the CC group (n= 126) did not show a significant difference in survival according to use of EGFR-TKIs [never vs. ever use of EGFR-TKIs; median OS, 14 (95% CI, 9-18) vs. 25 (95% CI, 23-27) months; log-rank test, P = 0.082]. On the other hand, the SNP of the EGF gene was not associated with response rate or progression-free survival of EGFR-TKIs.
Conclusions
These results suggested the genetic variants at the EGF gene might contribute to the survival difference associated with EGFR-TKI treatment in EGFR mutation-enriched patients.
Citation Format: Youngjoo Lee, Kyong-Ah Yoon, Jin Soo Lee. An association between genetic variant in Epidermal Growth Factor (EGF) gene and survival benefit from epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in never smokers with advanced adenocarcinoma of the lung. [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 4849. doi:10.1158/1538-7445.AM2013-4849
Abstract 4937: KIF3A promotes prostate cancer cell proliferation, migration, and invasion via activation of Dvl2 and the Wnt signaling pathway.
Authors: Liu Zun , Rebowe Ryan E. , Wang Zemin , Wang Zehua , DePaolo John S. , Guo Jianhui , Li Yingchun , Qian Chiping , Liu Wanguo 
Published: August 2014

Abstract
Aberrant activation of the Wnt signaling pathway is a key event in advanced prostate cancer. However, the mutations in APC complex that activate Wnt signaling in many other cancers are rare in prostate cancer. Other molecular mechanisms that regulate the Wnt signaling pathway in prostate cancer remain to be elucidated. Here we show that KIF3A, a subunit of kinesin-II motor protein, functions as an agonist of the Wnt signaling pathway in prostate cancer. KIF3A is up-regulated in the majority of human prostate cancer cell lines and primary tumor biopsies. The expression levels of KIF3A correlate with higher Gleason score, TNM grade, and metastatic status of prostate cancer. Moreover, overexpression of KIF3A stimulates the benign p69 prostate cell growth, whereas depletion of KIF3A by shRNA suppresses LNCaP cell proliferation, anchorage-independent growth, and cell migration/invasion. Mechanistically, we demonstrate that KIF3A activates DVL2 and induces transcriptional activation of Cyclin D1, HEF1, and MMP9 in prostate cancer cell lines that are required for cancer cell proliferation, migration, and invasion. Taking together, these findings indicate that KIF3A is a potent agonist of Wnt signaling in prostate cancer and suggest that up-regulation of KIF3A is causal of aberrant activation of Wnt signaling in advanced prostate cancer. Inactivation of KIF3A may improve survival of patients with advanced prostate cancer in which Wnt signaling is activated.
Citation Format: Zun Liu, Ryan E. Rebowe, Zemin Wang, Zehua Wang, John S. DePaolo, Jianhui Guo, Yingchun Li, Chiping Qian, Wanguo Liu. KIF3A promotes prostate cancer cell proliferation, migration, and invasion via activation of Dvl2 and the Wnt signaling pathway. [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 4937. doi:10.1158/1538-7445.AM2013-4937
Abstract 4989: Conditional NFAT activation promotes prostate oncogenesis through cell autonomous and non-cell autonomous effects.
Authors: Manda Kalyan Reddy , Tripathi Piyush , Wang Yinqiu , Humphrey Peter A. , Pan Minggui , Chen Feng 
Published: August 2014

Abstract
Although the activation of nuclear factor of activated T Cells (NFAT) has been linked to cellular transformation and its upregulation has been found in multiple tumor types, its potential role in prostate cancer (PCa) is unknown. We have recently found that NFATc1 activation in prostate epithelium results in prostatic intraepithelial neoplasia (PIN) that progresses to prostate adenocarcinoma in a Doxycycline (Dox)-inducible murine model. The adenocarcinoma primarily consists of Cytokeratin 8 (CK8)+, Androgen receptor (AR)+ luminal epithelial cells and reactive stroma with features similar to the most common types of human PCa. Both cells with NFATc1 activation and neighboring cells without NFATc1 activation have significant upregulation of c-Myc and activation of Stat3. Besides known and suspected NFATc1 targets, such as Spp1, we have revealed the early upregulation of a number of cytokines and cytokine receptors, as key molecular components of an inflammatory and pro-mitogenic microenvironment that promotes both NFATc1+ and NFATc1− cells to participate in tumor formation. Thus, NFATc1 activation has cell autonomous effects on the NFATc1+ cells and non-cell autonomous effects on neighboring cells through secreted factors, resulting in eciprocal prostatic epithelial-stromal interactions for promoting PCa development. Our studies present the first direct in vivo evidence that NFATc1 activation can induce PCa resembling human PCa and provide a versatile platform to further study the pathogenic mechanism of PCa.
Citation Format: Kalyan Reddy Manda, Piyush Tripathi, Yinqiu Wang, Peter A. Humphrey, Minggui Pan, Feng Chen. Conditional NFAT activation promotes prostate oncogenesis through cell autonomous and non-cell autonomous effects. [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 4989. doi:10.1158/1538-7445.AM2013-4989
Abstract 5060: Discrepancy between MMP-9 and its fibronectin-like domain in tumor growth and invasion.
Authors: Dayer Cynthia 
Published: August 2014

Abstract
Tumors are often compared to wounds that do not heal, where the crosstalk between tumor cells and their surrounding stroma is crucial at all stages of development from the initial primary growth to metastasis. Similar to wound healing, fibroblasts in the tumor stroma differentiate into myofibroblasts, also referred to as “cancer-associated fibroblasts” (CAFs), primarily, but not exclusively, in response to transforming growth factor-β (TGF-β). Myofibroblasts in turn enhance tumor progression by remodeling the stroma. Among molecules implicated in stromal remodeling, matrix metalloproteinases (MMPs), and MMP-9 in particular, play a prominent role. However, the mechanisms that regulate MMP-9 activation and function remain poorly understood. Recent evidence indicates that tumor cell surface association of MMP-9 is an important event in its activation, and more generally in tumor growth and invasion.
Based on these observations, we addressed the potential association of MMP-9 activity with cell-surface recruitment on human fibroblasts. We show for the first time that recruitment of MMP-9 to the MRC5 fibroblast cell surface occurs through the fibronectin-like (FN) domain, found only in MMP-9 and MMP-2. Functional assays suggest that the active form of MMP-9 triggers α-smooth muscle actin (αSMA) expression in resting fibroblasts that reflects myofibroblast differentiation, possibly through TGF-β activation.
Xenograft experiments using HT1080 fibrosarcoma or MDA-MD231 breast adenocarcinoma cells stably expressing the FN domain of MMP-9 in NOD/SCID mice revealed no changes in primary tumor growth. However, in the context of metastasis, expression of the FN domain by these same tumor cells dramatically increases their metastatic proclivity whereas expression of wt MMP-9 either promotes no change or actually reduces the number of metastases. Curiously, xenografts of SW480 colorectal adenocarcinoma cells stably expressing the FN domain of MMP-9 display reduced growth at both the primary (subcutaneous) injection site and the lungs, in experimental metastasis assays, of NOD/SCID mice. This discrepancy is believed to be due to the FN domain that may modulate MMP-9 activity and TGF-β activation in different ways, depending on the tumor cell type.
These observations suggest a dual role of MMP-9 and its FN domain in primary tumor growth and metastasis, underscoring the notion that the effect of MMP-9 on tumor cells may depend on their response to TGF-β activation and highlighting possible protective effects of MMPs in tumor progression and invasion.
Citation Format: Cynthia Dayer. Discrepancy between MMP-9 and its fibronectin-like domain in tumor growth and invasion. [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 5060. doi:10.1158/1538-7445.AM2013-5060
Abstract 5078: Response-guided anti-angiogenic therapy for hepatocellular carcinoma recurrence with clinically available safety agent.
Authors: Yoshiji Hitoshi , Noguchi Ryuichi , Kaji Kosuke , Aihara Yosuke , Namisaki Tadashi , Moriya Kei , Douhara Akitoshi , Kitade Mitsuteru , Fukui Hiroshi 
Published: August 2014

Abstract
The incidence of hepatocellular carcinoma (HCC) is increasing not only in Asia but also in Europe and United States. Since the high-risk group of either primary or secondary HCC development seems to be clearer than in the other types of tumors, it is likely that chemopreventive agents will be beneficial in improving the prognosis of HCC. No chemopreventive agent, however, has been approved against HCC yet. Since neovascularization plays a pivotal role in HCC, an angiostatic agent is considered as one of the promising approaches. Although an anti-angiogenic agent, sorafenib has approved for advanced heparocellular carcinoma (HCC), most of patients show adverse effects in liver cirrhosis. Insulin resistance (IR) is reportedly involved in the progression of HCC partly mediated with neovascularization. The aim of this study was to develop the response-guided anti-angiogenic therapy with a clinically used safe agent; branched-chain amino acid (BCAA), which reportedly possess anti-angiogenic and IR improving activities, for the cumulative recurrence of HCC after curative therapy. BCAA (Livact; 12 g/day) was administered after the curative therapy for HCC, and 60-month follow-up revealed that the BCAA markedly inhibited the cumulative recurrence of HCC under the condition of IR along with suppression of VEGF. Chronological studies reveled that the VEGF and AFP-L3 were significantly decreased in patients without recurrence at 6 and 12 months after the treatment, respectively. The soluble VEGFR (sVEGFR)-2 was significantly suppressed only in patients without recurrence, whereas sVEGFR-1 was not. A marked suppression of sVEGFR-2 could be achieved within only three months after the treatment. Collectively, since BCAA is widely and safely used in the clinical practice to treat the patients with chronic liver diseases, BCAA may represent a new strategy for secondary chemoprevention for the HCC patients with IR. Moreover, our findings suggest that sVEGFR-2 could become a useful response-guided predictive marker of anti-angiogenic therapy against HCC by BCAA under the condition of IR.
Citation Format: Hitoshi Yoshiji, Ryuichi Noguchi, Kosuke Kaji, Yosuke Aihara, Tadashi Namisaki, Kei Moriya, Akitoshi Douhara, Mitsuteru Kitade, Hiroshi Fukui. Response-guided anti-angiogenic therapy for hepatocellular carcinoma recurrence with clinically available safety agent. [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 5078. doi:10.1158/1538-7445.AM2013-5078
Abstract 5126: A poor prognosis subtype of HNSCC is consistently observed acrossmethylome, transcriptome and miRNome analysis.
Authors: Jung Alain C. , Job Sylvie , Ledrappier Sonia , Macabre Christine , Abecassis Joseph , de Reynies Aurélien , Wasylyk Bohdan 
Published: August 2014

Abstract
Background: Distant metastasis after treatment is observed in about 20% of Head and Neck Squamous Cell Carcinoma (HNSCC). In the absence of any validated robust biomarker, patients at higher risk for metastasis cannot be provided with appropriate therapy. In order to identify prognostic HNSCC molecular subgroups and potential biomarkers, we have performed genome-wide integrated analysis of four omic sets of data.
Material and methods: Using state-of-the art technologies, a core of 45 metastasizing and 52 non-metastasizing HNSCC patient samples were analyzed at four different levels: gene expression (transcriptome), DNA methylation (methylome), DNA copy number (genome) and miRNA expression (miRNome). Molecular subgroups were identified by a model-based clustering analysis, and their clinical relevance was evaluated by survival analysis.
Results: Transcriptome, methylome and miRNome patient subgroups with shorter metastasis-free survival were identified. A contingency analysis uncovered a R1 group of common tumors, which predicts metastasis occurrence with a higher statistical power than individual omic data sets. R1 and non-R1 samples display similar DNA copy number landscapes, but more frequent chromosomal aberrations are observed in the R1 cluster (especially loss at 13q14.2-3). R1 tumors are characterized by alterations of signaling pathways involved in cell-cell adhesion, EMT, immune response and apoptosis.
Conclusions: Integration of data across several omic profiles leads to better selection of patients at risk, identification of relevant molecular pathways of metastasis, and potential to discover biomarkers and drug targets.
Citation Format: Alain C. Jung, Sylvie Job, Sonia Ledrappier, Christine Macabre, Joseph Abecassis, Aurélien de Reynies, Bohdan Wasylyk. A poor prognosis subtype of HNSCC is consistently observed acrossmethylome, transcriptome and miRNome analysis. [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 5126. doi:10.1158/1538-7445.AM2013-5126
Abstract 5163: MMP3 increases expression of CXCL7.
Authors: Ju Donghong , Kosir Mary A. 
Published: August 2014

Abstract
MMP3 leads to epithelial-mesenchymal transformation (EMT) and malignant transformation of cultured cells. Previously, increased expression of the CXC chemokine CXCL7 was associated with EMT. The hypothesis tested is that MMP3 increases the expression of CXCL7
Methods: Human breast cells (MCF10AT (proliferative), MCFDCIS.com (in situ), MCFCA1a (malignant)) cultured in serum free medium were exposed to MMP-3 for 4 days, and washed 3 times with PBS, then cultured in MMP-3 free condition medium for three more days. Cells were collected every day for RNA extraction, and analyzed for relative CXCL7 gene expression using RT real time PCR. Cells sampled from day 0 were used as control to normalize the results. GADPH was control. Cells culture supernatant also collected every day for CXCL7 protein level expression. Protein concentrations were measured by enzyme-linked immunosorbent assay (ELISA) using human CXCL7/NAP-2 Duo set ELISA Development System.
Measurements were done in triplicate; results are representative of three experiments.
Results: When exposed to MMP-3, the CXCL7 RNA level increased MCF-10AT cells RNA level increased 1.5 fold, and there was no change in CXCL7 protein level in MCF-10AT cells. For MCFDCIS.com cells, the CXCL7 RNA level increased 2.5 fold, and CXCL7 protein level increased 1.6 fold. For MCFCA1a cells, the CXCL7 RNA level increased 2.6 fold, CXCL7 protein level increased 1.5 fold. The peak expression was 3-4 days. Removal of MMP-3 caused CXCL7 expression to return back to baseline in MCF10AT, DCIS.com and malignant Ca.cl1 cells.
Conclusion: The expression of chemokine CXCL7 in breast cell (MCF10AT, DCIS.com, MCFCA1a) was up regulated at both on RNA and protein level (except for MCF10AT) when exposed to MMP-3, and removal of MMP-3 caused CXCL7 expression to return to baseline. The stromal influence by MMP3 on breast cells and breast cancer cells may direct further progression toward the malignant phenotype and provides another therapeutic pathway target.
Citation Format: Donghong Ju, Mary A. Kosir. MMP3 increases expression of CXCL7. [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 5163. doi:10.1158/1538-7445.AM2013-5163