bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4180: Clonal evolution of tumor cell population in a patient with repetitively recurrent dermatofibrosarcoma protuberance (DFSP)
Authors: Oh Ensel , Choi Yoon-La , Ha Sang Yun , Lee Eun Hee , Lee Jeeyun , Kim Sung Joo , Kim Yu Jin , Song Ji-Young , Shin Young Kee , Jung Hae Min , Kwon Mi Jeong 
Published: May 2015

Abstract
It has been suggested that most tumors arise from a single cell of origin, and tumor progression results from acquired genetic variability within the original clone allowing sequential selection of more aggressive sublines. We investigated clonal evolution of tumor cell population with the tissues obtained from a sarcoma patient who experienced recurrence 4 times (in 2007, 2009, 2010, and 2012). Along the repetitive recurrences, we observed that the tumors which showed, initially, benign morphology and behaviors turned to be malignant from the 3rd recurrence. We performed whole exome sequencing to identify somatic mutations occurred in each recurrent tumor, and traced the change of tumor cell population. From the sequencing results, the COL1A1-PDGFB fusion which is a well-known oncogenic driver of DFSP was detected in all of the recurrent tumors, however, there was no other overlap of mutated genes between the 1st recurred tumor and the following ones. It suggests that there were at least two tumor cell populations which evolved independently after acquisition of oncogenic driver mutation, and the initial tumor cells which represented majority of the original tumor were replaced by the other tumor cells which survived from the systemic chemotherapy, and it finally led to a dramatic change in morphology and behavior of the tumor. We expect that the mutated genes in each population would give us a clue to understand the mechanism of malignancy of DFSP.
Citation Format: Ensel Oh, Yoon-La Choi, Sang Yun Ha, Eun Hee Lee, Jeeyun Lee, Sung Joo Kim, Yu Jin Kim, Ji-Young Song, Young Kee Shin, Hae Min Jung, Mi Jeong Kwon. Clonal evolution of tumor cell population in a patient with repetitively recurrent dermatofibrosarcoma protuberance (DFSP). [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4180. doi:10.1158/1538-7445.AM2014-4180
Abstract 4190: A survey of the most common methods of group randomization and distribution in preclinical in vivo studies
Authors: O'Brien Neil , Kumer Jeffrey L. , Ibsen Eric M. 
Published: May 2015

Abstract
To more closely emulate clinical research methodology and improve clinical relevance, researchers are increasingly utilizing clinically-similar group randomization and distribution methods for oncology studies in animals. One common pre-clinical approach, a random number generator in a spreadsheet, is paradoxically the least clinically-relevant, and subject to manual and transcription errors. This method provides no easy way to exclude animals from distribution based on other qualitative or quantitative data parameters. Due to limitations in spreadsheet software, commercially available pre-clinical trial applications can be used to perform the most recommended randomization and distribution methods based on tumor volume or other parameters: deterministic and matched distribution, pure randomization, stratified sampling randomization and block randomization across multiple numeric parameters. Subjects may be excluded initially based on recorded qualitative observations, and then by acceptable value ranges for numeric parameters. Animals can be randomized iteratively in rolling enrollment studies and previously randomized subjects can be re-randomized into new groups as required on drug-resistance studies. ANOVA results are displayed instantly to ensure similarity between groups. Standardizing randomization and distribution using clinically relevant methods improves the efficiency, clinical relevance, and outcome of animal studies relative to spreadsheet-based methods.
Citation Format: Neil O'Brien, Jeffrey L. Kumer, Eric M. Ibsen. A survey of the most common methods of group randomization and distribution in preclinical in vivo studies. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4190. doi:10.1158/1538-7445.AM2014-4190
Abstract 4191: Whole exome sequencing of a case of olfactory neuroblastoma
Authors: Cha SooJin , Lee Se-Hoon , Kim Jong-Il , Shin Jong-Yeon 
Published: May 2015

Abstract
Purpose: Olfactory neuroblastoma (ONB) is an unusual malignancy occurred in sinonasal tract and molecular characteristics were poorly understood. Here we analyzed sequence of a fresh tissue from an olfactory neuroblastoma patient through whole exome sequencing to identify ONB-specific mutations.
Methods: We examined fresh tumor sample with matched peripheral blood from a patient diagnosed olfactory neuroblastoma. All procedures were approved by IRB in Seoul National University Hospital. He was 30 years old and had chemotherapy, surgery and radiotherapy. He had a recurrent disease with metastasis to bones and lymph nodes, and tumor tissue was obtained from a lymph node. Genomic DNA was isolated from a dissected tissue and whole exome library was constructed using Agilent SureSelectXT Human All Exon V4+UTRs (71Mb). Sequencing was performed by Illumina HiSeq2000 platform with paired-end 101bp reads and sequenced data was aligned to human reference genome g1k v37 using Burrows-Wheeler Aligner (BWA). Then, a series of bioinformatical tools were used such as SAMtools, PICARD, the Genome Analysis Toolkit (GATK) and MuTect to list up potential candidate genes. These genes were filtered out considered as germline variants informed in database like dbSNP, 1000 genome project and exome sequencing project 6500 (esp6500). Final candidate genes were identified by manual curation based on cancer gene classification of public database and publications.
Results: Our approach generated 15Gb and 17Gb of mapped sequence, with 97.91% and 98.43% of the target regions covered at least 10X depth in tumor and normal sample, respectively. After processing and filtering, we identified 8 candidate cancer genes including 5 somatic nucleotide variants (SNVs; CDKN2C, NBPF1, NBPF10, TGFBR2 and TP53) and 3 insertion/deletion mutations (ACVR1B, AR and CARD11). Among SNVs, CDKN2C showed stopgain SNV resulted in truncated mutation and the same mutation in TP53 were recurrently reported in COSMIC database. Cancer gene candidate indel mutations included 2 frameshift insertions (ACVR1B and CARD11) and 1 nonframeshift insertion (AR).
Conclusions: We analyzed a patient of olfactory neuroblastoma using our WES pipeline and several genes were identified to candidate cancer gene mutations which should be validated in large number of samples.
Citation Format: SooJin Cha, Se-Hoon Lee, Jong-Il Kim, Jong-Yeon Shin. Whole exome sequencing of a case of olfactory neuroblastoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4191. doi:10.1158/1538-7445.AM2014-4191
Abstract 4197: Regulators of p21 transcription in melanoma
Authors: Bøe Sigurd L. , Thingnes Josef , Golmakani Sima Z. , Hovig Eivind 
Published: May 2015

Abstract
p21(CIP1/WAF1) is a cyclin-dependent kinase inhibitor that directly inhibits the activity of cyclin E/CDK2 and cyclin D/CDK4/6 complexes and thereby functions as a regulator of cell cycle progression. The transcriptional regulation of p21 has been reported to be controlled by a large number of genes. However, the importance of each of these genes upon p21 transcriptional expression in melanoma is not fully explored. Here we have measured p21 mRNA levels in a cell panel consisting of 17 cell melanoma lines with various genetic backgrounds, spanning various stages of the disease. A correlation between p21 expression and p53 status in these cell lines demonstrated low p21 expression in p53 mutant cell lines, such as WM1366, MeWo, SKMEL28, WM45.1, WM983 and WM852 compared to cell lines with wild-type p53. With the use of a number of small molecular inhibitors against the MAPK and cAMP pathways to investigate possible changes in the p21 expression levels, we find that p21 expression levels were more sensitive to regulation by inhibitors in the p53 mutant cell lines compared to cell lines with p53 wild-type. Furthermore, we investigated mRNA expression levels of around 20 genes that previously have been reported to be involved in the regulation of p21 expression, and we find that TBX2 and TBX3 mRNA levels showed the strongest correlation with p21 mRNA levels.
Citation Format: Sigurd L. Bøe, Josef Thingnes, Sima Z. Golmakani, Eivind Hovig. Regulators of p21 transcription in melanoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4197. doi:10.1158/1538-7445.AM2014-4197
Abstract 4198: cAMP signaling in BRAFV600E melanoma
Authors: Rodriguez Carlos I. 
Published: May 2015

Abstract
G-protein coupled receptor (GPCR) signaling, predominantly the cyclic AMP (cAMP) signaling, is crucial for melanocyte proliferation and differentiation. Previous studies have shown a downregulation in cAMP signaling in mutant NRAS melanoma. However, no relationship has been reported about cAMP signaling in mutant BRAF melanoma, which makes up about 60% of all cutaneous melanoma. Here, we studied the role of four main G-protein signaling pathways using reporters for Gαs (cAMP Response Element, CRE), Gαq (inositol triphosphate signaling, NFAT-RE), Gα12 (RhoA signaling, SRF-RE) and Gβγ (MAPK pathway, SRE), in melanoma. Our data show that cAMP signaling is substantially more constitutively active in BRAFV600E mutant melanoma than NRAS mutant melanoma. Moreover, hyperactivation of cAMP signaling decreases proliferation and migration in BRAFV600E. Interestingly, in a melanoma cell line with neither BRAF nor NRAS mutation, cAMP hyperactivation increased proliferation. Furthermore, BRAFV600E inhibition increases constitutive cAMP activity. These results show a possible crosstalk between cAMP signaling and BRAFV600E in melanoma.
Citation Format: Carlos I. Rodriguez. cAMP signaling in BRAFV600E melanoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4198. doi:10.1158/1538-7445.AM2014-4198
Abstract 4199: Riluzole modulates the production of exosomes in melanoma cells
Authors: Isola Allison L. , Wen Yvonne , Goydos James , Chen Suzie 
Published: May 2015

Abstract
Exosomes are naturally occurring small membrane enclosed microvesicles generated constitutively and released by various cell types and more frequently released by tumor cells. It was postulated that exosomes may facilitate communication within the local microenvironment and the primary tumor, supporting melanoma cell dissemination and early events in metastasis. A gain-of-function mutation of a neuronal receptor, metabotropic glutamate receptor 1 (GRM1), when ectopically expressed in melanocytes, was sufficient to induce in vitro melanocytic transformation and spontaneous malignant melanoma development in vivo in a transgenic mouse model. Normal mouse melanocytes transformed with an expression vector containing GRM1 showed production and secretion of exosomes confirmed by electron microscopy, while the parental normal melanocytes showed no detectable presence of exosomes. In light of this data, It was hypothesized that over-expression of GRM1 in melanoma cells normally expressing a moderate amount of the protein, may promote elevated levels of exosome formation, while inhibitors to the receptor or limiting the levels of available ligand may suppress exosome production. Preliminary results demonstrated the working hypothesis is correct. Our earlier studies showed that inhibitors of the receptor modulated GRM1-mediated signaling events interfere with downstream effectors resulting in a decrease in both cell proliferation in vitro and tumor progression in vivo. It is not known if GRM1 acts directly, via its signaling cascade, or by another route, on exosome production regulation, this will be investigated. In addition to the pharmacological inhibitors we will also use a genetic approach with silencing RNA to modulate GRM1 expression levels.
Citation Format: Allison L. Isola, Yvonne Wen, James Goydos, Suzie Chen. Riluzole modulates the production of exosomes in melanoma cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4199. doi:10.1158/1538-7445.AM2014-4199
Abstract 42: TRPM7 expression predicts poor prognosis in patients with nasopharyngeal carcinoma and correlates with tumor metastasis
Authors: Chen Jian-Peng , Sun Guiqin , Wang Wei-Bo , Wang Cai-Xia 
Published: May 2015

Abstract
The aim of this study was to investigate prognostic significance of TRPM7 expression in nasopharyngeal carcinoma (NPC) and evaluate the association of TRPM7 with tumor invasion and metastasis. Immunohistochemical staining for TRPM7 was carried out on paraffin-embedded tissue sections from 206 NPC patients. The data was subjected to statistical analysis with respect to clinicopathological variables and survival. Real-time PCR and Western blot were used to assess the expression of TRPM7 in NPC cells. Small interfering RNA and construct transfection were used to knockdown and improve TRPM7 expression in NPC cells. TRPM7 was highly expressed in 102 out of 206 (49.5%) NPC cases. TRPM7 expression was significantly correlated with clinical stage, lymphatic and distant metastasis. The patients who had high TRPM7 expression showed a significantly lower 5 year survival rate than the patients who had low TRPM7 expression. TRPM7 might be an independent prognostic indicator for patient's survival. The cell lines with high metastatic potential expressed more TRPM7 than the cell lines with low metastatic potential. Moreover, the migratory and invasive potential of NPC cells was significantly decreased and increased by TRPM7 knockdown and overexpression. The study indicates that TRPM7 expression is inversely correlated with NPC patient survival and correlated with NPC invasion and metastasis.
Note: This abstract was not presented at the meeting.
Citation Format: Jian-Peng Chen, Guiqin Sun, Wei-Bo Wang, Cai-Xia Wang. TRPM7 expression predicts poor prognosis in patients with nasopharyngeal carcinoma and correlates with tumor metastasis. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 42. doi:10.1158/1538-7445.AM2014-42
Abstract 4201: Activation of p90 ribosomal S6 kinase (RSK) and downstream targets are directly regulated by S100B protein in malignant melanoma
Authors: Pierce Adam D. 
Published: May 2015

Abstract
S100B is an effective and extensively used prognostic marker for melanoma, with increasing serum levels of S100B being predictive of disease stage, increased recurrence, and low overall patient survival. We have recently identified a mechanism by which S100B alters ERK-RSK signaling to facilitate the progression of melanoma. Elucidation of this novel mechanism will aid the development of new pharmacological drugs to inhibit tumor progression. We have identified and characterized several ERK-RSK downstream targets regulated by S100B expression. These data are consistent with a mechanism in which elevated S100B binds directly to RSK in a calcium-dependent manner to prevent ERK-mediated phosphorylation of RSK. Our structural studies have further elucidated the S100B-RSK interaction as a novel drug target in melanoma cells and we are currently screening compounds for inhibitors of the S100B-RSK interaction.
Citation Format: Adam D. Pierce. Activation of p90 ribosomal S6 kinase (RSK) and downstream targets are directly regulated by S100B protein in malignant melanoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4201. doi:10.1158/1538-7445.AM2014-4201
Abstract 4202: Deciphering the effects of GNA13 mutations in B-cell lymphomas
Authors: O'Hayre Morgan L. , Kufareva Irina , Vaqué Jose P. , Piris Miguel A. , Gutkind J. Silvio 
Published: May 2015

Abstract
G-proteins and their cognate G-protein coupled receptors (GPCRs) are critical signal transduction molecules that regulate cell survival, proliferation, motility and differentiation. The aberrant expression or function of these molecules has been linked to growth, progression and metastasis of various cancers. Recent genome-wide sequencing efforts have unveiled numerous previously uncharacterized mutations in G-proteins and GPCRs, which could have significant implications to cancer initiation and progression. Of interest, recent analyses have demonstrated that there are frequent mutations in GNA13 in Burkitt's lymphoma and Diffuse Large B cell lymphomas (DLBCL) that are highly statistically significant over background cancer gene mutation rate, and occur in ∼10-13% of patients with these lymphomas. Mutations in the downstream target of G13, RhoA, are also present in several Burkitt's lymphoma tumors, highlighting that mutations in this G13-RhoA pathway may be key to the oncogenic potential of these B cell lymphomas. Although G13 activity has previously been linked cellular transformation and metastatic potential of epithelial cancers, our data suggests that the mutations in GNA13 in these B cell lymphomas are mostly inhibitory in nature. Thus, we have functionally characterized several mutations in GNA13 and RHOA found in Burkitt's lymphoma and DLBCL.
Citation Format: Morgan L. O'Hayre, Irina Kufareva, Jose P. Vaqué, Miguel A. Piris, J. Silvio Gutkind. Deciphering the effects of GNA13 mutations in B-cell lymphomas. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4202. doi:10.1158/1538-7445.AM2014-4202
Abstract 421: Differences of DNA methylation patterns according to histologic subtypes of early gastric carcinomas
Authors: Mia-Jan Khalilullah , Ryu Hoon , Lee Mi-Ra , Ji Sun-Young , Cho Mee-Yon 
Published: May 2015

Abstract
Background: The DNA methylation change is known to play a crucial role in early gastric carcinogenesis. However, its association with the histologic subtypes of EGCs has not been fully elucidated. In this study, we aim to know whether the subtypes of early gastric carcinomas (EGCs) are related to the differences of DNA methylation or not using genome wide methylation assay. Materials and Method: The comprehensive methylation analysis was performed by Illumina Infinium methylation assay (IIMA, 450K BeadChip kit) covering 450,000 sites on 12 tumors and 12 matched non-tumor mucosa from 12 patients with EGC. Hisytologically, the EGCs were devided into intestinal type (group A, n=6) and non-intestinal type (group B, diffuse=4 and mixed=2). The CpG sites in 450K microarray chip are classified into CpG islands, shores (2kb), shelves (2kb∼4kb) and open sea (&gt;4kb) by CpG content and neighborhood context. According to the functional genomic distribution they are classified into promoter, body, 3′UTR and intergenic. To determine DMRs, average β-values were computed with β-values in signal intensity of over 3000. The Δβ-value was a result substracted average β-value of one from the other. When Δβ is over 0.2 or below -0.2, it was considered to be meaningful and refered to differentially methylated regions (DMRs) . Results: There were 484 DMRs in group A tumor and 208 DMRs in group B. The pattern of DMRs were different between two groups. In group A tumor, most of DMRs (97.73%) were hypermethylated and 75.26% were in CpG island. On the other hand, the group B tumors showed that 63.94% of DMRs were hypermethylated and only less than half of them (48.87%) were in CpG island. In terms of functional genomic distribution of DMRs, promoter (38.66%) was the most common site in group A while body (54.14%) was in group B. On Hierarchical clustering analysis, the clear grouping was made by 208 DMRs in three cases, two of them being mixed-type, by both correlation and Euclidean methods. However, no distinct grouping was found with DMRs in group A. Hierarchical clustering analysis of non-tumor mucosa showed a distinct separation between group A and B. Conclusions: DNA methylation pattern was distinctively different between the histologic subtype of EGCs. In the intestinal type of EGCs, the DNA methylation seems to be started in non-tumor mucosa.
Citation Format: Khalilullah Mia-Jan, Hoon Ryu, Mi-Ra Lee, Sun-Young Ji, Mee-Yon Cho. Differences of DNA methylation patterns according to histologic subtypes of early gastric carcinomas. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 421. doi:10.1158/1538-7445.AM2014-421
Abstract 4210: CPAP contributes to HBx-mediated NF-κB activation in hepatocellular carcinoma
Authors: Hung Liang-Yi 
Published: May 2015

Abstract
Hepatocellular carcinoma (HCC) is a type of tumor that results from chronic inflammation triggered by hepatotropic viruses or other toxic chemicals. Constitutive activation of nuclear factor (NF)-κB is an important event involved in chronic inflammation of the liver. The HBV X protein (HBx) is shown to activate NF-κB by inducing phosphorylation of IκBα and decreasing IκBα stability. Centrosomal protein P4.1-associated protein (CPAP), which plays important roles in centrosomal functions, is previously identified as the transcriptional co-activator of NF-κB. Herein, we demonstrate that CPAP can directly interact with HBx to enhance HBx-mediated NF-κB activation. Knockdown expression of CPAP abolishes this effect, indicating that CPAP is required for HBx-mediated NF-κB activation. In addition, HBx cooperates with cyclic adenosine monophosphate response element-binding protein (CREB) to increase the expression of CPAP by up-regulating its promoter activity. Furthermore, overexpression of CPAP enhances the protein stability of HBx. These results suggest that a positive feedback regulation exists between CPAP and HBx. The stable expression of CPAP in HCC cell lines increases cell proliferation. In addition, the co-expression of CPAP and HBx more greatly enhances the cell proliferation ability than either CPAP or HBx alone. Taken together, our study indicates that CPAP can cooperate with HBx and is important for HBx-induced NF-κB activation.
Citation Format: Liang-Yi Hung. CPAP contributes to HBx-mediated NF-κB activation in hepatocellular carcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4210. doi:10.1158/1538-7445.AM2014-4210