bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2459: Membrane type 1 matrix metalloproteinase and integrin-linked kinase: A characterization of potential partners in ovarian cancer metastasis
Authors: Bruney Lana , Stack Sharon 
Published: August 2012

Abstract
Epithelial ovarian cancer (EOC) is the fifth leading cause of overall cancer death among American women. In 2010, 15,520 deaths were directly attributed to EOC; and 21,650 additional cases were diagnosed. When EOC is diagnosed prior to metastatic dissemination, the overall 5 year survival rate is 93%; however, over 75% of women with EOC are diagnosed with metastasis already present, dropping the survival rate to less than 20%. The process of EOC metastasis is unique in that epithelial cells detach from the primary tumor and shed into the peritoneal cavity as single cells and multicellular aggregates (MCA), which adhere intraperitoneally and invade the interstitial collagen-rich submesothelial matrix, where they proliferate to anchor secondary lesions. Proteolytic activity promotes the migration and collagen invasion crucial to metastatic success. Also key to cell migratory activity are focal adhesions (FA), integrin- and protease-rich cell adhesion sites that physically link the actin cytoskeleton to the extracellular matrix (ECM) and transduce signals into the intracellular compartment. Sites of adhesive contacts with collagen fibers have been associated with beta-1 integrin clustering and various matrix metalloproteinases. Membrane type 1 matrix metalloproteinase (MT1-MMP), an ECM degrading protease localized to the cell surface, has been shown to promote a collagen-invasive phenotype in ovarian carcinomas. Additionally, collagen-activated integrin-linked kinase (ILK), a beta-1 integrin cytoplasmic domain interactor, has been shown to regulate several biological processes that promote invasion and suppress anoikis. As initial steps to assess the contributions and potential inter-relationships of tumor cell invasion at FAs, presented here is a characterization of MT1-MMP and ILK expression in select ovarian cancer cell lines and in human EOC tumor tissue microarrays.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2459. doi:1538-7445.AM2012-2459
Abstract 2469: Increased cathepsin B expression in cultured tuberous sclerosis skin tumor cells and patient tumor tissues
Authors: Li Shaowei , Liu Ying , Wang Ji-an , Moss Joel , Darling Thomas N. 
Published: August 2012

Abstract
Skin hamartomas in tuberous sclerosis complex (TSC) are disfiguring red tumors that contain fibroblast-like cells, vessels, fibrous tissue, and elongated hair follicles. Our recent studies show that TSC skin tumor cells induce angiogenesis and hair follicle neogenesis in a xenograft mouse model. These morphogenic changes are likely caused by altered expression of proteins involved in tissue remodeling. To identify such factors, we carried out 2-D gel analysis of cell extracts of TSC2-null fibroblasts derived from a TSC periungual fibroma (PF) compared to fibroblasts from patient normal-appearing skin (NL). PF cells had greater levels of all three forms of cathepsin B than TSC normal fibroblasts. Cathepsin B, a member of the lysosomal cysteine proteases family that has been implicated in angiogenesis and extracellular matrix remodeling, exists in pro-, single chain and double chain forms, and these were increased in PF cells by 1.6-, 2.3- and 8.3-fold, respectively. Western blot analysis of TSC skin tumor fibroblasts from 5 patients showed dramatically greater levels of active cathepsin B than in paired patient NL fibroblasts. Tumor cells from PFs showed greater intracellular cathepsin B enzyme activity than NL controls. Western blot and ELISA analysis showed that media conditioned by TSC skin tumor cells from 5 different patients contained 4.1- to 36-fold more procathepsin B than media conditioned by NL fibroblasts. Immunohistochemical staining of TSC patient angiofibromas and PFs showed greater numbers of cathepsin B-positive cells than patient normal-appearing skin. These results suggest that TSC skin tumor cells may induce hamartoma morphogenesis through expressing and releasing high level of cathepsin B.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2469. doi:1538-7445.AM2012-2469
Abstract 2475: The abundance of SLC7a11 transporter in different tissues
Authors: Kondapalli Lavanya , Huang Ying , Lambros Maria P. 
Published: August 2012

Abstract
The purpose of this study is to investigate the abundance of the SLC7A11 transporter in different tissues. The SLC7A11 is a plasma membrane transporter which mediates the transport of one cystine into the cell in exchange for one intracellular glutamate. We performed RT-PCR and immunohistochemistry to demonstrate the abundance of SLC7A11 transporter in different tissues. Tissue array slides were purchased from US Biomax Inc. The tissues were stained with or without SLC7A11 primary antibody. The images were captured using the software NIS elements connected to Nikon Eclipse series microscope. The images were then analyzed for staining intensity compared to their negative controls by using the software, Imagej. Panc-1, BxPC-3 and MIAPaCa-2 are human pancreatic cancer cell lines which were purchased from ATCC. The cells were cultured at 370C in humidified atmosphere of 5% CO2 using MEM or RPMI medium with low cystine levels. RNA was extracted from all the cell lines and converted into cDNA for Real Time PCR analysis. PCR reactions were prepared using SYBR green (which acts as a nucleic acid stain), forward and reverse SLC7A11 or GAPDH primers, and diluted cDNA. The reactions were added into 96-well PCR strips and sealed to prevent evaporation of the samples. The ABI 7300 machine was run after configuring the software and finally analyzed using 7300 system SDS software. The immunohistochemistry images demonstrate that most cancers especially pancreatic cancers have a high abundance of SLC7A11 transporter compared to normal tissues. The RT-PCR results showed that PANC-1 has significantly higher SLC7A11 expression compared to BxPC-3 and MIAPaCa-2 cell lines. The results indicate that SLC7A11 transporter is highly expressed in cancer tissues.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2475. doi:1538-7445.AM2012-2475
Abstract 2478: Jagged 2 signalling is active in Langerhans cell histiocytosis and confers pathognomonic features on dendritic cells
Authors: Hutter Caroline , Kauer Max , Jug Gunhild , Simonitsch Ingrid , Kovar Heinrich , Gadner Helmut 
Published: August 2012

Abstract
Langerhans cell histiocytosis (LCH) is an enigmatic disease defined by the accumulation of eponymous Langerhans-cell-like cells of unknown origin. It is a rare disease that may affect any age group, although its most severe clinical course affects predominantly young children. The clinical manifestations range from single lesions that can resolve spontaneously to systemic disease that requires intensive chemotherapy and bone marrow transplantation. Here we demonstrate that LCH cells exhibit a unique transcription profile that clearly separates them from indigenous dendritic cells (DCs), i.e. Langerhans cells, myeloid dendritic cells, and plasmacytoid dendritic cells, indicating a distinct DC entity that occurs under pathologic conditions. Molecular analysis revealed that LCH cells selectively expressed NOTCH ligand Jagged 2 (JAG2) and were the only DCs that coexpressed both NOTCH ligand and receptor. In line, activated NOTCH was detected in LCH but not control biopsies. Furthermore, we show that JAG2 signalling induces key LCH markers CD1a and Langerin on MoDCs, suggesting a role of NOTCH signalling in LCH ontogenesis. Interestingly, JAG2 also strongly induced matrix-metalloproteinase (MMP) 1 in MoDCs, which is highly expressed in LCH lesions and mediates massive tissue destruction and remodelling. The MMP induction by JAG2 was selective for DCs and not recapitulated in monocytes. Together these findings strongly suggest that Jagged2 mediated NOTCH activation confers phenotypic and functional aspects of LCH to DCs. Thus, interference with NOTCH signalling may prove an attractive target to combat this disease.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2478. doi:1538-7445.AM2012-2478
Abstract 248: JNK-FoxO3a dependent apoptosis in quercetin treated MDA-MB-231 human breast cancer cells
Authors: Kim Haesung , Choi Byung-Soo , Lee Sang-Soo , Kim Lee-Su , Ryu Byung-Yoon , Nam Ju-Suk 
Published: August 2012

Abstract
FoxO transcription factors are well known as key tumor suppressors in mammalian cells. The suppression of FoxOs in cancer cells is thought to be mainly due to activation of multiple onco-kinases, such as Akt and SGK, by a phosphorylation-ubiquitylation-mediated cascade. On the other hand, phosphorlyation of FoxO by JNK relocalizes it from the cytoplasm to the nucleus allowing transcription of FoxO target genes. In this study, we applied human breast cancer cells to determine whether the activity of FoxO3a is regulated during the quercetin mediated apoptosis. After treatment with the indicated amount of quercetin (5-80uM) for 5days, the growth of human breast cancer cell lines including MDA-MB-231, MDA-MB-486 and MCF-7 cells was reduced in dose- and time-dependent manner. FACS analysis with AnnexinV/PI double staining showed that the proportion of early apoptotic cancer cells were significantly increased in quercetin treated cells. It represents the potent apoptotic effect of quercetin in breast cancer cells. Furthermore, a marked elevation of FoxO3a transcriptional activity was detected at 20μM of quercetin using FHRE-reporter assay, as well as increased protein level of FoxO3a was detected by western blotting. And also it was determined that the activation of FoxO3a lead to the upregulation of FasL expression during the apoptotic process. To identify the signaling mechanism of FoxO3a regulation, we examined the activation of several well known upstream kinases such as Akt, Erk, IKKβ, AMPK and JNK. Notably, a significant increase of JNK phosphorylation was observed in quercetin treated cells. In addition, the inhibition study with pharmacological inhibitor (SP600125) showed that the involvement of JNK for the regulation of FoxO3a activity is critical in quercetin treated breast cancer cells. These results demonstrate that quercetin induces FoxO3a-related apoptosis by activation of JNK in MDA-MB-231 cells, and suggest the possibility that JNK-FoxO3a signaling pathway contributes mainly to the apoptotic process of breast cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 248. doi:1538-7445.AM2012-248
Abstract 2482: Carnitine palmitoyltransferase 1A (CPT1A): a transcriptional target of PAX3-FKHR and mediates PAX3-FKHR-dependent motility in alveolar rhabdomyosarcoma cells
Authors: Liu Lingling , Chen Taosheng 
Published: August 2012

Abstract
Alveolar rhabdomyosarcoma (ARMS) has a high propensity to metastasize, leading to its aggressiveness and a poor survival rate among those with the disease. More than 80% of aggressive ARMSs harbor a PAX3-FKHR fusion transcription factor, which regulates cell migration and promotes metastasis, most likely by regulating the fusion protein's transcriptional targets. Therefore, identifying druggable transcription targets of PAX3-FKHR that are also downstream effectors of PAX3-FKHR-mediated cell migration and metastasis may lead to novel therapeutic approaches for treating ARMS. To identify genes whose expression is directly affected by the level of PAX3-FKHR in an ARMS cellular-context, we first developed an ARMS cell line in which PAX3-FKHR is stably down-regulated, and showed that stably downregulating PAX3-FKHR in ARMS cells significantly decreased the cells’ motility. We also found that when PAX3-FKHR was downregulated, the expression level of carnitine palmitoyltransferase 1A (CPT1A) decreased. Analysis of the CPT1A promoter identified 4 putative PAX3-FKHR binding sites. Results of mutational analysis, promoter reporter assays, and electrophoretic mobility shift assays showed that PAX3-FKHR binds directly and specifically to a paired-domain binding-site in the CPT1A promoter region, indicating that CPT1A is a novel direct transcriptional target of PAX3-FKHR. Downregulating CPT1A, either by gene knockdown or by using a pharmacologic modulator of CPT1A activity, decreased cell motility in ARMS cells. Taken together, we have identified CPT1A as a novel direct transcriptional target of PAX3-FKHR and revealed the novel function of CPT1A in promoting cell motility. CPT1A may represent a novel therapeutic target for the treatment of ARMS.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2482. doi:1538-7445.AM2012-2482
Abstract 2484: Whole-exome sequencing of a rare case of familial childhood acute lymphoblastic leukemia
Authors: Healy Jasmine , Saillour Virginie , Spinella Jean-François , Vidal Ramon , Bareke Eric , Richer Chantal , Larivière Mathieu , Busche Stephan , Ge Bing , Montpetit Alexandre , Pastinen Tomi , Sinnett Daniel 
Published: August 2012

Abstract
Acute lymphoblastic leukemia (ALL) is the most common cancer in children, accounting for approximately 25% of all pediatric cancer cases. However, familial childhood ALL is extremely rare. Few families with multiple non-twinned siblings diagnosed with childhood ALL have been reported, and to date no highly penetrant leukemia susceptibility gene(s) has been identified to explain this uncommon occurrence. We postulated that pure (nonsyndromic) familial childhood ALL could result from the accumulation of disadvantaging rare DNA variants in predisposing genes or biological pathways. To address this hypothesis, we used next-generation sequencing technologies to capture and re-sequence the whole-exomes of a family comprising the mother, father and two male non-twinned affected siblings (sibling A and sibling B). Both brothers were diagnosed with the identical ALL subtype, pre-B hyperdiploid childhood ALL, three years apart. The similar clinical and molecular characteristics of the siblings suggest shared etiologic factors. Using the Agilent SureSelect All Human Exon 38 Mb Kit and the SOLiD 3 Plus system, we captured and sequenced a total of 17.5 Gb of sequence for the entire family, with a mean coverage of 47X. For each individual, approximately 96% or 36.4 Mb of the targeted bases were covered α1X and 70% of the targeted bases or 26.4 Mb passed our thresholds for variant calling. We identified 52,038 positions at which the called allele(s) differed from the reference genome in at least one of the four family members. In total, we identified 19,096 germline variants in sibling A and 28,061 in sibling B, of which 2,355 (12.3%) and 2,125 (7.6%), respectively, were previously undiscovered in dbSNP. We investigated non-synonymous homozygous variant and compound heterozygous positions shared between the siblings, as well as genes/pathways with increased burden of rare non-synonymous variants. Based on several criteria (PolyPhen annotation, known allele frequency, etc.), we identified variants that are strong functional candidates to explain this case of pure familial childhood ALL. In parallel, high-density genotyping was also performed (Illumina Omni 2.5M) for quality control and structural variant detection, allowing the identification of putatively shared copy number variants that may also be involved in leukemogenesis. Though independent validation and functional assessment is required, this is the first study to identify genetic factors involved in pure familial childhood ALL.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2484. doi:1538-7445.AM2012-2484
Abstract 2487: CONSERTING: an accurate method for detecting focal and gross somatic copy number alterations in cancer genome by next generation sequencing
Authors: Chen Xiang , Wang Jianmin , Roberts Kathryn , Pounds Stanley , Dyer Michael , Mullighan Charles , Downing James , Zhang Jinghui 
Published: August 2012

Abstract
The Identification of somatically acquired DNA copy number alterations (CNA) is extremely important for finding causal genes in cancer. Although next-generation sequencing (NGS) can assay a genome at base-pair resolution, accurate identification of CNA from NGS data has been hindered by sequencing artifacts, coverage bias and paralogous genomic duplication. As a result, existing algorithms tend to generate many CNA segments that are not corroborated by an alternative assay such as SNP array, suggesting high false discovery rate. To improve CNA analysis for NGS data, we developed Copy Number Segmentation by Regression Tree in Next Generation Sequencing (CONSERTING), a novel copy number detection method that integrates read depth analysis with structural variation (SV) detection and adjustment for sequencing artifacts. Analysis of simulated data shown that CONSERTING outperforms existing methods by achieving high sensitivity of focal copy number detection (CONSERTING: 0.80, CNV-Seq: 0.26, SegSeq: 0.19, FREEC: 0.02) at a low false discovery rate (CONSERTING: 0.09, CNV-Seq: 0.19, SegSeq: 0.46, FREEC: 0.07). When applied to matching tumor/normal samples of hematopoietic malignancies and solid tumors, CONSERTING showed a high concordance with SNP array, with a mean of 18 uncorroborated CNA segments compared with 104 by CNVSeq, 182 by SegSeq and 63 by FREEC. In addition, CONSERTING is able to discover bona fide focal CNAs in genes of biological importance that were not detectable by SNP array, such as a 36 kb homozygous deletion in SH2B3 and a 20 kb deletion in CDK6. Finally, CONSERTING is able to find CNAs and SVs present in tumor subclone that are missed by SNP array or SV analysis of NGS data. The novel CNAs and SVs reported here were experimentally validated, demonstrating that the high sensitivity and accuracy of CONSERTING enable discovery of key genetic lesions in cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2487. doi:1538-7445.AM2012-2487
Abstract 2492: Integrated genomics on molecular subgroups in medulloblastoma
Authors: Kool Marcel , Jones David T.W. , Remke Marc , Jaeger Nathalie , Korshunov Andrey , Schlanstein Maria , Northcott Paul A. , van Meeteren Netteke Schouten , van Vuurden Dannis , Clifford Steven C , Pietsch Torsten , Von Bueren Andre O. , Rutkowski Stefan , Cho Yoon-Jae , McCabe Martin , Collins Peter , Haberler Christine , Ellison David , Gilbertson Richard , Pomeroy Scott , Doz Francois , Delattre Olivier , Taylor Michael D. , Lichter Peter , Pfister Stefan M. 
Published: August 2012

Abstract
Medulloblastoma is the most common malignant brain tumor in childhood. Molecular studies from several groups around the world demonstrated that medulloblastoma is not one disease but comprises a collection of distinct molecular subgroups. However, all these studies reported on different numbers of subgroups. The current consensus is that there are only four major subgroups, which are now called WNT, SHH, Group 3 and Group 4. A better understanding of each of these molecular subtypes is urgently warranted to improve treatment strategies and the overall survival of patients and ultimately also the quality of life for those that survive medulloblastoma. We used the data of seven independent studies on medulloblastoma for further characterization of these molecular subtypes. All cases (n = 550) were analyzed by expression profiling and for most cases SNP or array-CGH data were available. Data are presented for all medulloblastomas together and for each subgroup separately. For validation purposes we compared the results of this meta-analysis with another large medulloblastoma cohort (n = 408) for which subgroup information was obtained by immunohistochemistry. Results from both cohorts are highly similar and show how distinct the molecular subtypes are with respect to their transcriptome, DNA copy number aberrations, demographics, and survival. Interestingly, the data also showed how different medulloblastomas are between infants, children and adults. In infants, for instance, almost all medulloblastomas are classified as SHH or Group 3, whereas in adults most medulloblastomas are of the SHH subtype and almost never of Group 3. Recent next generation sequencing data (whole genome and exome) generated in our laboratory for a large series of pediatric and adult medulloblastomas show that the spectrum of genetic mutations is also very different, not only between the molecular subtypes, but also between the different age categories. All these data clearly show that medulloblastoma is not one disease. Results from these molecular analyses will form the basis for prospective multi-center studies and will have an impact on how the different variants of medulloblastoma will be treated in the future.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2492. doi:1538-7445.AM2012-2492