bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1896: Bioluminescent assays for investigating cell metabolism.
Authors: Leippe Donna , Sobol Mary , Duellman Sarah , Vidugiriene Jolanta , Zhou Wenhui , Vidugiris Gediminas , Good Troy , Bernad Laurent , Meisenheimer Poncho , Cali James 
Published: August 2014

Abstract
Cell metabolism is an important and expanding area of research in the field of cancer biology. Simple, rapid assays for studying cellular metabolic pathways, their enzymes, metabolites and cofactors can facilitate these studies. We have developed two novel bioluminescent technologies, one for monitoring cell viability, and the other for monitoring changes in cellular nicotinamide adenine dinucleotides, that can facilitate the study of cell metabolism and its regulation.
The bioluminescent cell viability assay is based on the metabolic activity of live cells. Metabolically active cells reduce a proluminogenic substrate in vivo which is then detected by a luciferase enzyme in the media. The luminescence output is correlated with the number of viable cells. The assay is non-toxic, sensitive (detects less than 10 cells/well) and has a large dynamic range (S/B&gt;100). The key, differentiating feature of this assay is the incorporation of the recently developed stable and very bright NanoLuc™ luciferase and its profurimazine substrate, which allows changes in viability to be monitored in real-time and continuously, over extended periods of time, from the same sample.
Three homogeneous, one-step, bioluminescent assays have been developed for the detection of nicotinamide adenine dinucleotides, specific for: (1) reduced forms NADH and NADPH, (2) non-phosphorylated forms NAD and NADH, and (3) phosphorylated forms NADP and NADPH. The assays are based on the reaction of the enzyme diaphorase with a proluciferin substrate, which in the presence of NADH or NADPH is converted to luciferin, a substrate for luciferase. These assays are sensitive (LOD ≤ 50 nM) and have large maximum signal windows (S/B &gt; 100), two advantages over currently available colorimetric and fluorescent detection methods. They are also robust, and amenable to automated and high-throughput protocols (Z’ &gt; 0.8). The high sensitivity, one-step reagent addition, and no requirement for sample processing, permit an in-well protocol for the assay of cells directly in culture plate wells. Changes in cellular NAD levels can be rapidly monitored, as demonstrated using FK866, an inhibitor of NAD biosynthesis. FK866 caused a decrease in NAD levels in multiple cell types with good signal windows (S/B &gt; 10) and expected pharmacology (IC50 values = 1-10 nM).
Citation Format: Donna Leippe, Mary Sobol, Sarah Duellman, Jolanta Vidugiriene, Wenhui Zhou, Gediminas Vidugiris, Troy Good, Laurent Bernad, Poncho Meisenheimer, James Cali. Bioluminescent assays for investigating cell metabolism. [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 1896. doi:10.1158/1538-7445.AM2013-1896
Abstract 1900: Hypoxia induces accumulation of lysosomal proteins within mitochondria.
Authors: Nakamura Yasuyuki , Yoshida Masaki , Kitamura Noriaki , Kamino Hiroki , Murai Ryuya , Saito Yuri , Sano Hitoya , Arakawa Hirofumi 
Published: August 2014

Abstract
Mitochondrial quality control (MQC) plays a critical role in maintaining a healthy status of mitochondria, preventing aging, cancer, and a variety of degenerative diseases. However, the mechanism largely remains unclear. Recently, we discovered a novel MQC mechanism regulated by Mieap, a p53-inducible protein, in which Mieap induces intramitochondrial lysosome-like organella that plays a critical role in the elimination of oxidized mitochondrial proteins (designated MALM for Mieap-induced accumulation of lysosome-like organelles within mitochondria) in response to mitochondrial damage (1-4). Here, we report a physiological role of the MALM function. Hypoxia dramatically induced accumulation of lysosomal proteins within mitochondria without the destruction of mitochondrial structure in both human normal mammary epithelial cells (HMEC4s) and mouse embryonic fibroblasts cells (MEFs). In response to the hypoxic stress, the MALM was inducible in ATG5-KO, ATG7-KO, and PINK1-KO MEFs, but not in p53-KO and Mieap-KO MEFs, suggesting that the phenomenon is completely different from canonical autophagy. In the MALM-deficient cells, hypoxia caused an increase of mitochondrial reactive oxygen species (ROS) generation and accumulation of oxidized proteins within the mitochondria. Surprisingly, the MALM-deficient cells in the hypoxic condition revealed enhanced activities of cell migration and invasion. This phenotype was totally cancelled by a ROS scavenger reagent, Ebselen. These results suggest that the MALM is a universal and fundamental function in the cell (at least from mouse to human), which plays a critical role in MQC under hypoxia. Alteration of the MALM function in cancer cells could facilitate cancer invasion and metastasis via mitochondrial ROS generated by unhealthy mitochondria.
1. Miyamoto Y et al. PLoS ONE 6: e16054, 2011
2. Kitamura N et al. PLoS ONE 6: e16060, 2011
3. Nakamura Y et al. PLoS ONE 7: e30767, 2012
4. Miyamoto T et al. Sci Rep 2: 379, 2012
Citation Format: Yasuyuki Nakamura, Masaki Yoshida, Noriaki Kitamura, Hiroki Kamino, Ryuya Murai, Yuri Saito, Hitoya Sano, Hirofumi Arakawa. Hypoxia induces accumulation of lysosomal proteins within mitochondria. [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 1900. doi:10.1158/1538-7445.AM2013-1900
Abstract 1913: FGFR1 amplification as a druggable target in lung squamous cell carcinoma.
Authors: Kwon Mi Jung , Lee Seung Eun , Han Joungho , Ahn Jin Seok , Park Keunchil , Kim Jhingook , Ahn Myung-Ju , Choi Yoon-La 
Published: August 2014

Abstract
Background: Focal gene amplification is a potential target for diagnosis and therapy in cancer. Fibroblast growth factor receptor-type 1 (FGFR1) may play a role in the pathogenesis of lung squamous cell carcinoma (LSCC) and amplification of the FGFR1 gene is considered a candidate target for treatment of LSCC. The aim of this study was to simultaneously explore copy number changes of FGFR1 and 23 other genes by multiplex ligation-dependent probe amplification (MLPA), to compare the results with fluorescent in situ hybridization (FISH) data, and determine the clinicopathological significance of gene amplification.
Methods: This study included 81 resected LSCC specimens obtained between 2008 and 2010, and 14 lung cancer cell lines. MLPA was performed using fresh tumor samples and cell lines and FISH was applied to formalin-fixed, paraffin-embedded tissues.
Results: MLPA showed amplification/gain of MYC (48.1% of LSCCs), AURKA (44.4%), MET (29.6%), KIT (21.0%), and FGFR1 (14.8%). FISH showed FGFR1 amplification in 22 LSCCs (27.2%) using a cut-off value of ≥5. There was high concordance between FISH and MLPA (85.2%). No association between FGFR1 amplification and any clinicopathological variables was observed; however, associations were identified between EGFR and FGFR1 FISH-amplified tumors; PDGFRA and poor differentiation; KDR, ABL1, and MET and age; and SMO and CCND2 and pT stages.
Conclusions: Our MLPA and FISH data showed that FGFR1 amplification is a common event, occurring in 15-27.2% of LSCCs. Other amplified genes may be also candidate targets for the treatment of LSCC.
Citation Format: Mi Jung Kwon, Seung Eun Lee, Joungho Han, Jin Seok Ahn, Keunchil Park, Jhingook Kim, Myung-Ju Ahn, Yoon-La Choi. FGFR1 amplification as a druggable target in lung squamous cell 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 1913. doi:10.1158/1538-7445.AM2013-1913
Abstract 1935: Expression of human Piwi-like genes is associated with prognosis for soft tissue sarcoma patients and is different in gender.
Authors: Greither Thomas , Koser Franziska , Kappler Matthias , Bache Matthias , Lautenschläger Christine , Goebel Steffen , Holzhausen Hans-Jürgen , Wach Sven , Würl Peter , Taubert Helge W. 
Published: August 2014

Abstract
The family of Argonaute genes is essential for stem cell maintenance and RNA interference. Piwi-like genes as a subclass of the Argonaute genes are expressed mainly in the germline. However, these genes may be re-expressed in tumors, and expression of the Piwi-like genes is associated with prognosis in several types of tumors.
We analyzed the expression of
Piwi-like mRNAs (Piwi-like 2-4) in
125 soft tissue sarcoma (STS) samples by qPCRs. Statistical tests were applied to study the correlation of expression levels with tumor-specific survival for
STS patients.
In multivariate Cox's regression analyses, we detected that low Piwi-like
2 and Piwi-like 4 mRNA expression were significantly associated with a worse prognosis (RR = 1.87; p = 0.032 and
RR = 1.82; p = 0.039). In addition, low expression of both genes was associated with a 2.58-fold increased risk of tumor-related death (p = 0.01).
Next we analysed expression of Piwi-like genes gender specific. Piwi-like 4 and combined Piwi-like 2 and 4 mRNA levels correlated significantly with prognosis (RR = 3.53; p
= 0.002 and RR = 5.23; p = 0.004) only for female but not for male patients.
However, combined low Piwi-like 2 and
3 transcript levels were associated with worse survival (RR = 5.90; p = 0.02) for male patients.
In this study, we identified a significant association between the expression of Piwi-like 2 and 4 mRNAs and the tumor-specific survival of soft tissue sarcoma patients. A connection between gender and the impact of Piwi-like mRNA expressions on STS patients’ prognosis was shown for the first time.
Citation Format: Thomas Greither, Franziska Koser, Matthias Kappler, Matthias Bache, Christine Lautenschläger, Steffen Goebel, Hans-Jürgen Holzhausen, Sven Wach, Peter Würl, Helge W. Taubert. Expression of human Piwi-like genes is associated with prognosis for soft tissue sarcoma patients and is different in gender. [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 1935. doi:10.1158/1538-7445.AM2013-1935
Abstract 1961: Overexpression of miR-196b and HOXA10 characterize a poor-prognosis gastric cancer subtype.
Authors: Lim Jae Yun , Yoon Sun Och , Seol So-Young , Hong Soon Won , Kim Jong Won , Choi Seung Ho , Lee Ju-Seog , Cho Jae Yong 
Published: August 2014

Abstract
Background: Gastric cancer is composed of disease subgroups with heterogeneous clinical and biological behaviors. A previous study identified two subgroups with distinct gene-expression profiles strongly associated with prognosis. To identify molecular biologic differences between these two subgroups, we performed an integrative analysis of mRNA, microRNA, and protein expression.
Methods: Array technologies were used to generate microRNA and protein expression profiles of frozen tissue samples from 60 patients with gastric cancer. All patients underwent curative gastric resection in 2005 and distributed from stage I to IV and their clinical characteristics were collected. BRB-ArrayTools were used for microarray data analysis. Data was compared between gastric cancer tissue and normal gastric tissue and also between two different prognostic groups. Aberrantly expressed microRNA and associated mRNA in patients with poor-prognosis gastric cancer were validated by quantitative RT-PCR and tissue microarray, respectively.
Results: Four microRNAs were aberrantly expressed in gastric cancer tissue, especially poor prognostic group (P &lt; 0.05). In the poor-prognosis subgroup, miR-196b showed the most significantly high expression patterns and also miR-135b, miR-93. On the contrary, miR-29c* was down-regulated. MiR-196b expression was positively correlated with HOXA10 expression (r = 0.726; P &lt; 0.001), which was significantly increased in poor-prognosis patients (P &lt; 0.001). HOXA10 protein-positive expression was identified in 56 of 368 gastric cancer tissue microarray samples. In reverse-phase protein array, 46/124 proteins were expressed differently (P &lt; 0.05); COX2 (P &lt; 0.001) and cyclin B1 (P = 0.017) were clearly over-expressed in the poor-prognosis group.
Conclusion: Integrative analysis of RNA and protein expression profile facilitates interpretation of the molecular biologic heterogeneity of cancer. Co-activation of miR-196b and HOXA10 characterized a poor-prognosis subgroup of patients with gastric cancer. As HOXA10 is involved in the proliferation of hematopoietic stem cells and progenitor cells, the relevance of hematopoietic progenitor cell and gastric cancer development/progression should be further investigated.
Citation Format: Jae Yun Lim, Sun Och Yoon, So-Young Seol, Soon Won Hong, Jong Won Kim, Seung Ho Choi, Ju-Seog Lee, Jae Yong Cho. Overexpression of miR-196b and HOXA10 characterize a poor-prognosis gastric cancer subtype. [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 1961. doi:10.1158/1538-7445.AM2013-1961
Abstract 1967: Rb dephosphorylation and cleavage in Apoptosis.
Authors: Antonucci Lisa , Lentine Brandon , De Leon Gabriel , Krucher Nancy A. 
Published: August 2014

Abstract
The Retinoblastoma protein (Rb) is important in the control of cell proliferation and apoptosis. Its activity is controlled by reversible phosphorylation on several serine and threonine residues. The role of Rb phosphorylation in the control of apoptosis is largely unknown, although several apoptotic stimuli result in dephosphorylation of Rb. We have recently shown that dephosphorylation of Threonine-821 of Rb is required for apoptosis triggered by UV radiation and by the cdk inhibitor, Roscovitine. Here we show that Roscovitine induced dephosphorylation of Threonine-821 occurred concomitant with C-terminal cleavage of Rb, which is a known marker of apoptosis. In attempt to characterize the role of Rb dephosphorylation in the process of Rb cleavage, we have utilized mouse embryonic fibroblasts (MEFs) that express a mutant Rb in which the carboxy-terminal caspase cleavage site (884DEADG888) of Rb is altered to DEAAE which is resistant to cleavage (RB-MI). Roscovitine treatment (8 hours, 25μM) causes a reduction in cell number in WT MEFs, but has no effect on RB-MI MEFs. In addition, Roscovitine causes apoptosis in 60-70% of WT MEFs, however Roscovitine is unable to induce apoptosis in RB-MI MEFs demonstrating that the cdk inhibitor requires the carboxy-terminal cleavage of Rb in order to stimulate apoptosis. Apoptosis was measured using a DNA fragmentation ELISA, TUNEL assay, and by immunoblotting of active caspase-3. Experiments are currently underway to determine whether dephosphorylation of Threonine-821, specifically, is required for Rb cleavage.
Citation Format: Lisa Antonucci, Brandon Lentine, Gabriel De Leon, Nancy A. Krucher. Rb dephosphorylation and cleavage in Apoptosis. [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 1967. doi:10.1158/1538-7445.AM2013-1967
Abstract 1972: Clinical impact of 6q deletion patterns in prostate cancer.
Authors: Kluth Martina , Amschler Nina , Heinl Anna , Jung Simon , Simon Ronald , Schlomm Thorsten , Sauter Guido , Minner Sarah Jane Pauline 
Published: August 2014

Abstract
Deletions of chromosome 6q12-22 represent the second common deletion in prostate cancer. Although most of these deletions are large and span &gt; 50 megabases, a minimal deleted region containing 3-4 megabases was described at 6q15. MAP3K7 (at 6q15) was suggested as a potential target gene in this area. Based on the hypothesis, that large 6q deletions compromising a multitude of genes may have a different impact on the biology of prostate cancer cells than small circumscribed 6q15 deletions, a tissue microarray (TMA) containing over 7000 prostate cancers was analyzed by fluorescence in situ hybridization (FISH). All cancers were analyzed with probes for 6q12, 6q14, 6q15 (MAP3K7), 6q16, and 6q22. 3888 tumors were interpretable for all 5 probes including 463 (10.6%) showing a 6q deletion. 6q deletions were tightly linked to a negative ERG status with 15.6% deletions in ERG negative and 5.8% deletions in ERG positive cancers (p&lt;0.0001). The frequency of 6q deletions increased with Gleason grade and pT stage. 6q deletions were found in 5.4% of ≤3+3, 10.6% of 3+4, 19.6% of 4+3, and 18.8% of ≥4+4 cancers (p&lt;0.0001). 6q deletions occurred in 9.6% of pT2, 11.5% of pT3a, and 14.8% of pT3b carcinomas (p=0.0160). 6q deletions were also linked to early PSA recurrence (p&lt;0.0001). Remarkably, the clinical outcome varied markedly with deletion size. PSA recurrence was more likely in cancers with 6q12-22 deletions as compared to tumors with 6q14-16 deletions (p&lt;0.0001). Twelve genes located within 6q14-16 were functionally evaluated applying colony formation assays to prostate cell lines BPH1, DU-145, and PC-3. These analyses failed to identify a cell behavior consistent with a role as a tumor suppressor gene for MAP3K7, as well as RRAGD, ANKRD6, LYRM2, MDN1, CASP8AP2, BACH2, COQ3, MANEA, RNGTT, SLC35A1, and MMS22L. In conclusion, the strong impact of the deletion size suggests, that multiple genes on chromosome 6q12-22 might have a tumor suppressive role in prostate cancer and that alterations of more than one of these has an additive adverse effect to cells. Our data do not confirm MAP3K7 as the main target of 6q deletions in prostate cancer
Citation Format: Martina Kluth, Nina Amschler, Anna Heinl, Simon Jung, Ronald Simon, Thorsten Schlomm, Guido Sauter, Sarah Jane Pauline Minner. Clinical impact of 6q deletion patterns in prostate 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 1972. doi:10.1158/1538-7445.AM2013-1972
Abstract 1974: Functional characterization of Basonuclin 1 (BNC1): a novel tumor suppressor gene commonly downregulated in human prostate cancer.
Authors: Kwabi-Addo Bernard , Wang Songping , Furbert-Harris Paulett , Yegnasubramanian Srinivasan , Devaney Joseph 
Published: August 2014

Abstract
Prostate cancer (PCa) harbors a myriad of aberrant genomic and epigenetic alterations. Epigenetic inactivation of genes in PCa is largely based on transcriptional silencing by aberrant CpG methylation of CpG rich promoter regions. To better understand the role of aberrant methylation changes and to identify biological pathways likely to be affected in PCa, we used a genome-wide methylation array from Illumina (Infunium) to identify novel methylated genes associated to PCa. We identified several candidate genes including BNC1 as novel genes which are frequently methylated and whose methylation closely related to inactivation of gene expression in prostate cancer cell lines. Basonuclin1 is a zinc finger transcription factor that interacts with a subset of promoters of genes transcribed by both RNA polymerase-I and -II and has roles in maintaining ribosomal biogenesis and the proliferative potential of immature epithelial cells. We found that the expression of BNC1 negatively correlated with the degree of methylation at the CpG island in prostate tumor samples compared to benign prostate tissues. The forced-expression of BNC1 significantly decreased prostate cancer cell proliferation whereas the siRNA mediated BNC1 knock-down increased prostate cancer cell proliferation. Overall, our data suggest a potential tumor suppressor role for BNC1 that includes regulation of cell proliferation and cell-cell interaction in prostate carcinogenesis.
Citation Format: Bernard Kwabi-Addo, Songping Wang, Paulett Furbert-Harris, Srinivasan Yegnasubramanian, Joseph Devaney. Functional characterization of Basonuclin 1 (BNC1): a novel tumor suppressor gene commonly downregulated in human prostate 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 1974. doi:10.1158/1538-7445.AM2013-1974
Abstract 1979: Tripartite motif 14 (TRIM14) is a putative tumor suppressor gene in non-small-cell lung cancer.
Authors: Hai Josephine , Tsao Ming-Sound 
Published: August 2014

Abstract
Background: Non-small-cell lung carcinoma (NSCLC) accounts for 85% of all malignant lung tumors. Our group previously identified Tripartite Motif 14 (TRIM14) as a component of a prognostic multigene expression signature for NSCLC patients. TRIM14 belongs to a conserved family of Tripartite Motif-encoding genes that are involved in a broad range of biological processes, such as transcriptional regulation, cell proliferation, and apoptosis. However, TRIM14 itself is poorly understood, especially in the context of cancer progression. Here we investigate the biological function of TRIM14 in NSCLC.
Methods: The expression of TRIM14 was modified in human NSCLC cell lines (NCI-H1395, NCI-H1650 and NCI-H157) by lentivirus-mediated overexpression and short-hairpin RNA-mediated silencing. Effects were assessed by examining in vitro cell proliferation and anchorage-independent growth, and in vivo tumorigenicity in mice.
Results: In vitro studies show that TRIM14 overexpression in NSCLC cells suppresses proliferation and anchorage-independent growth, whereas knock-down of TRIM14 expression promotes cell proliferation and colony formation. In vivo studies demonstrate that knock-down of TRIM14 expression significantly increases tumor growth in immunodeficient mice.
Conclusion: This is the first study to suggest that TRIM14 may function as a tumor suppressor gene in lung cancer, affecting cell proliferation and anchorage-independent growth in vitro and tumor growth in mice.
(Supported by Canadian Cancer Society Research Institute grant #020527)
Citation Format: Josephine Hai, Ming-Sound Tsao. Tripartite motif 14 (TRIM14) is a putative tumor suppressor gene 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 1979. doi:10.1158/1538-7445.AM2013-1979