bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1990: Loss of Olfactomedin 4 gene leads to neoplastic progression in the murine prostate.
Authors: Li Hongzhen , Liu Wenli , Zhu Jianqiong , Chen Weiping , Deng Chu-Xia , Rodgers Griffin P. 
Published: August 2014

Abstract
The murine olfactomedin 4 gene (Olfm4) encodes an olfactomedin-related glycoprotein whose physiological and pathological functions in the prostate are largely unknown. We have observed that homozygous Olfm4 mutant mice develop prostatic intra epithelial neoplisa (PIN), high grade PIN, adenocarcinoma and metastatic tumor in an age-dependent manner. We also found that increased proliferation of prostate epithelial cells in Olfm4-null mice. In this report, we studied the mechanisms underlying neoplastic progression of Olfm4-deficient mice prostate. We have performed microarray analysis to compare Olfm4 knockout and wild-type mice prostate at 3 and 15 months of ages. A total of 187 genes were found commonly changed in both 3 and 15 months, whereas 894 and 1090 genes were significantly changed in 3 and 15 months respectively. Enrichment Gene Go Diseases analysis showed prostatic neoplasms was at the top of 10 listed diseases. We found that 95 genes for neoplastic procession markers were significantly changed in the prostate of Olfm4-deficient mice. Among the genes, 39 genes were up-regulated and 37 genes were down regulated more than 1.5-fold. The qRT-PCR confirmed consistently higher expression of Ets1, Vav3, Shh, Sdc2, and Mmp19, and down-regulation of the genes Rnasel and Psca in Olfm4 knockout mice compared with Olfm4 wild-type mice. We also confirmed expression of Ets1 and Mmp19 by using western blot and immunohistochemistry analysis.
Interestingly, in the GEO prostate cancer database, which compares tumor to normal tissue and metastatic tumor to normal tissue, expression of OLFM4 and RNASEL were down-regulated, in contrast, expression of ETS1 and MMP19 were up-regulated. Therefore, the gene expression profiles in the GEO database confirmed and extended Ets1, Mmp19 and Rnasel in Olfm4 knockout mice. Our finding indicates that loss of OLFM4 leads to progression of prostate cancer.
Citation Format: Hongzhen Li, Wenli Liu, Jianqiong Zhu, Weiping Chen, Chu-Xia Deng, Griffin P. Rodgers. Loss of Olfactomedin 4 gene leads to neoplastic progression in the murine prostate. [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 1990. doi:10.1158/1538-7445.AM2013-1990
Abstract 1991: PDCD4 de-repression of Bcl-xl IRES-mediated translation leads to enhanced chemo-resistance of glioblastoma multiforme tumors.
Authors: Liwak Urszula , Jordan Lindsay E. , Roncaroli Federico , Holcik Martin 
Published: August 2014

Abstract
Glioblastoma multiforme (GBM) is the most prevalent form of tumor of the central nervous system with an average survival time of less than one year. Given the location and characteristics of GBM only limited treatment options are available, thus understanding the mechanisms of GBM formation or progression may lead to the development of novel treatment options. Strikingly, a common feature of GBM is the loss of expression of the tumor suppressor programmed cell death 4 (PDCD4) which correlates with adverse outcomes for patients in response to chemo- or radiation therapy. Through both transcriptional and translational regulation, PDCD4 has been shown to regulate many proteins within the cell, although the precise mechanism of target selection is not known. We have hypothesised that silencing of PDCD4 in glioblastomas leads to an altered expression of apoptosis-regulating proteins resulting in the suppression of apoptotic signals and enhanced chemo-resistance. Indeed, we show that low levels of PDCD4 correlate with an increase in the anti-apoptotic Bcl-xL protein. Importantly, Bcl-xL is regulated at the level of protein synthesis through the internal ribosome entry site (IRES) in its 5’ untranslated region (UTR). We further show that PDCD4 regulates the activity of the Bcl-xL IRES, and is therefore an IRES specific translational regulator. Importantly, reintroduction of PDCD4 into glioblastoma cells or directly inhibiting Bcl-xL with the chemical inhibitor ABT-737 sensitizes these cells to doxorubicin, thus enhancing cell death. In summary, our work provides a novel role for PDCD4 as a translational regulator of Bcl-xL as well as a potential therapeutic option for the treatment of GBM.
Citation Format: Urszula Liwak, Lindsay E. Jordan, Federico Roncaroli, Martin Holcik. PDCD4 de-repression of Bcl-xl IRES-mediated translation leads to enhanced chemo-resistance of glioblastoma multiforme tumors. [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 1991. doi:10.1158/1538-7445.AM2013-1991
Abstract 1994: Smurf2 mediates ubiquitination and degradation of YY1 to suppress B-cell proliferation and lymphomagenesis.
Authors: Ramkumar Charusheila , Cui Hang , Kong Yahui , Jones Stephen , Gerstein Rachel , Zhang Hong 
Published: August 2014

Abstract
Current treatment of diffuse large B-cell lymphoma (DLBCL), the most common type of non-Hodgkin's lymphoma, has improved patient survival significantly. However, 40-50% of DLBCL patients still die from this disease. There is a critical need to better understand the specific molecular pathways that are perturbed in DLBCL for the development of new and effective therapeutic approaches. We show that mice deficient in the E3 ubiquitin ligase Smurf2 spontaneously develop B-cell lymphomas that resemble human DLBCL with molecular features of germinal center B cells. We discover that Smurf2 mediates ubiquitination and degradation of YY1, a key germinal center transcription factor. Importantly, Smurf2 deficiency enhances YY1-mediated transactivation of c-Myc and B-cell proliferation. Furthermore, the expression of Smurf2 is significantly decreased in primary human DLBCL samples compared to normal B cells, and low levels of Smurf2 expression correlate with poor survival prognosis in DLBCL patients. The Smurf2-YY1-c-Myc regulatory axis represents a novel pathway perturbed in DLBCL that suppresses B-cell proliferation and lymphomagenesis, suggesting Smurf2 as a new therapeutic paradigm for DLBCL.
Citation Format: Charusheila Ramkumar, Hang Cui, Yahui Kong, Stephen Jones, Rachel Gerstein, Hong Zhang. Smurf2 mediates ubiquitination and degradation of YY1 to suppress B-cell proliferation and lymphomagenesis. [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 1994. doi:10.1158/1538-7445.AM2013-1994
Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
Abstract 1995: GKN1-miR-185-DNMT1 axis suppresses gastric carcinogenesis through regulation of epigenetic alteration and cell cycle.
Authors: Yoon Jung Hwan , Choi Won Suk , Park Won Sang , Kim Olga 
Published: August 2014

Abstract
Gastrokine 1 (GKN1) functions to protect the gastric antral mucosa and promotes healing by facilitating restitution and proliferation after injury. GKN1 is down-regulated in Helicobacter pylori-infected gastric epithelial cells and that loss of GKN1 expression is tightly associated with gastric carcinogenesis, but underlying mechanisms as tumor suppressor are largely unknown. In the present study, we demonstrated that restoration of GKN1 protein suppressed gastric cancer cell growth by inducing endogenous miR-185 that directly targets epigenetic effectors, DNMT1 and EZH2 in gastric cancer cells. Notably, GKN1 expression was inversely correlated with DNMT1 and EZH2 expression in a subset of gastric cancer tissues and various gastric cancer cell lines. In addition, ectopic expression of GKN1 suppressed histone deacetylase 1 and thereby induced cell cycle arrest via regulating cell cycle proteins in gastric cancer cells. Interestingly, it was found that regulatory domains of the GKN1, pGKN1D13N, pGKN1▵68-199 and pGKN1▵1-67, 165-199 recapitulated GKN1 functions, and GKN1 exerted synergistic anti-cancer effect with 5-FU on tumor cell growth implying that the amino-terminal regulatory motif and brichos domain of GKN1 are sufficient for its tumor suppressor activities and thereby suggesting therapeutic intervention of gastric cancer. Collectively, our results demonstrated that loss of GKN1 functions occur and that cause aberrant expression of DMNT1 and EZH2 by suppression of endogenous miR-185 contributing malignant gastric epithelial cell proliferation and transformation in gastric carcinogenesis.
Citation Format: Jung Hwan Yoon, Won Suk Choi, Won Sang Park, Olga Kim. GKN1-miR-185-DNMT1 axis suppresses gastric carcinogenesis through regulation of epigenetic alteration and cell cycle. [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 1995. doi:10.1158/1538-7445.AM2013-1995
Abstract 1999: A targeted exome sequencing platform for routine clinical molecular profiling of advanced thoracic malignancies relevant to targeted therapy.
Authors: Lau Christopher C. , Killian Keith , Zhu Yuelin J. , Wang Yonghong , Pineda Marbin , Thomas Anish , Wang Yisong , Morrow Betsy , Xi Liqiang , Raffeld Mark , Giaccone Giuseppe , Meltzer Paul S. 
Published: August 2014

Abstract
Increasing number of oncogenic mutations important to the clinical management of advanced thoracic malignancies is being identified. To translate this into routine clinical testing environment, we developed and validated a targeted exome sequencing method using next generation sequencing (NGS) technology that is designed to detect both single nucleotide variants and short insertions or deletions (indels) by employing a custom designed target selection system. In each individual assay, 197 cancer related genes, including 12 clinically relevant genes (AKT1, AKT2, BRAF, EGFR, ERBB2, HRAS, KIT, KRAS, MEK1, NRAS, PIK3CA, and PTEN) are simultaneously sequenced from 100-500ng of total DNA extracted from formalin-fixed paraffin-embedded (FFPE) tissue. To date, we have performed this assay on over 250 FFPE tissues from Non-Small-Cell Lung Cancers (NSCLC), Small-Cell Lung Cancers (SCLC), and thymic malignancies. Mutations in all 12 clinically relevant genes including EGFR L858R, KRAS codon 12 missense mutations as well as EGFR exon 19 deletions, EGFR exon 20 insertions, and ERBB2 exon 20 insertions have been identified and validated with alternate technology in approximately 30% of all samples tested. Compared with conventional capillary sequencing, which typically requires in excess of 25% mutant DNA, this assay can detect mutations with 5% - 10% mutant allele frequency. This is a robust, reliable and cost effective assay that not only is suitable for prospective molecular profiling of clinically relevant targets, but also provides a powerful tool for retrospective analysis of existing FFPE tissues from clinical trials.
Citation Format: Christopher C. Lau, Keith Killian, Yuelin J. Zhu, Yonghong Wang, Marbin Pineda, Anish Thomas, Yisong Wang, Betsy Morrow, Liqiang Xi, Mark Raffeld, Giuseppe Giaccone, Paul S. Meltzer. A targeted exome sequencing platform for routine clinical molecular profiling of advanced thoracic malignancies relevant to targeted therapy. [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 1999. doi:10.1158/1538-7445.AM2013-1999
Abstract 200: EGCG inhibits pancreatic cancer stem cell characteristics in human primary tumors, and carcinogenesis in KrasG12D transgenic mice.
Authors: Marsh Luke , Tang Su-Ni , Nall Dara , Jackman Chris , Shankar Sharmila , Srivastava Rakesh K. 
Published: August 2014

Abstract
EGCG, a component of green tea, exerts antiproliferative and proapoptotic actions on a number of different cancer cell lines through diverse mechanisms. However, the mechanisms by which EGCG inhibits cell proliferation and induces apoptosis are poorly understood. The objectives of this study were to examine the molecular mechanisms by which EGCG inhibits stem cell characteristics of pancreatic cancer stem cells (CSCs) derived from human primary tumors and carcinogenesis in KrasG12D transgenic mice. Human pancreatic CSCs (CD133+CD44+CD24+ESA+) are highly tumorigenic and form subcutaneous tumors in NOD/SCID IL2R gamma mice. Human pancreatic CSCs expressing high levels of CD133, CD24, CD44, ESA, and aldehyde dehydrogenase also express significantly more Nanog, Oct-4, Notch1, MDR1 and ABCG2 than normal pancreatic tissues and primary pancreatic cancer cells. Similarly, CSCs from KrasG12D mice express significantly high levels of pluripotency maintaining factors than pancreatic tissues from Pdx-Cre mice. EGCG inhibits the growth (size and weight) and development (PanIN lesions) of pancreatic cancer in KrasG12D mice by suppressing the activation of Kras, ERK, AKT and FoxO. EGCG inhibits the self-renewal capacity of pancreatic CSCs derived from human primary tumors and KrasG12D mice. EGCG inhibits pluripotency maintaining factors (Nanog, Sox-2, c-Myc and Oct-4) and drug resistance gene ABCG2 in CSCs. Inhibition of Nanog by shRNA enhances the inhibitory effects of EGCG on self-renewal capacity of CSCs. Finally, EGCG inhibits CSC's migration and invasion and markers of epithelial-mesenchymal transition (Zeb-1, Slug and Snail). These data suggest that EGCG can inhibit pancreatic cancer development in human and KrasG12D transgenic mice by inhibiting stem cell characteristics. In conclusion, EGCG can be used for the management of pancreatic cancer.
Citation Format: Luke Marsh, Su-Ni Tang, Dara Nall, Chris Jackman, Sharmila Shankar, Rakesh K. Srivastava. EGCG inhibits pancreatic cancer stem cell characteristics in human primary tumors, and carcinogenesis in KrasG12D transgenic mice. [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 200. doi:10.1158/1538-7445.AM2013-200
Abstract 2000: Impact of delay to cryopreservation on RNA integrity and genome-wide expression profiles in resected tumor samples.
Authors: Le Calvez-Kelm Florence , Caboux Elodie , Paciencia Maria , Durand Geoffroy , Robinot Nivonirina , Wozniak Magdalena , Galateau-Salle Francoise , Byrnes Graham , Hainaut Pierre 
Published: August 2014

Abstract
Background: The quality of tissue samples and extracted mRNA is a major source of variability in tumor transcriptome analysis using genome-wide expression microarrays. During and immediately after surgical tumor resection, tissues are exposed to metabolic, biochemical and physical stresses characterized as “warm ischemia”. Current practice advocates cryopreservation of biosamples within 30 minutes of resection, but this recommendation has not been systematically validated by measurements of mRNA decay over time.
Methods: Using Illumina HumanHT-12 v3 Expression BeadChips, providing a genome-wide coverage of over 24,000 genes, we have analysed gene expression variation in samples of 3 hepatocellular carcinomas (HCC) and 3 lung carcinomas (LC) cryopreserved at times up to 2 hours after resection.
Results: RNA Integrity Numbers (RIN) revealed no significant deterioration of mRNA up to 2 hours after resection. Genome-wide transcriptome analysis detected non-significant gene expression variations of -2.4%/hr (95% CI: -5.5%/hr to 0.6%/hr; p=0.12). In LC, no consistent gene expression pattern was detected in relation with warm ischemia. In HCC, a signature of 6 up-regulated genes (CYP2E1, IGLL1, CABYR, CLDN2, NQO1, SCL13A5) and 6 down-regulated (MT1G, MT1H, MT1E, MT1F, HABP2, SPINK1) was identified (FDR &lt;0.05).
Conclusions: Overall, our observations support current recommendation of time to cryopreservation of up to 30 minutes and emphasize the need for identifying tissue-specific genes deregulated following resection to avoid misinterpreting expression changes induced by warm ischemia as pathologically significant changes.
Citation Format: Florence Le Calvez-Kelm, Elodie Caboux, Maria Paciencia, Geoffroy Durand, Nivonirina Robinot, Magdalena Wozniak, Francoise Galateau-Salle, Graham Byrnes, Pierre Hainaut. Impact of delay to cryopreservation on RNA integrity and genome-wide expression profiles in resected tumor samples. [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 2000. doi:10.1158/1538-7445.AM2013-2000
Abstract 2004: International Cancer Genome Consortium (ICGC).
Authors: Hudson Thomas J. , Jennings Jennifer L. 
Published: August 2014

Abstract
The International Cancer Genome Consortium (ICGC) was established to bring together researchers from around the globe to comprehensively analyze the genomic, transcriptomic, and epigenomic changes in 50 different tumour types or subtypes that are of clinical and societal importance across the globe (International network of cancer genome projects. Nature 464, 993-998 (15 April 2010)).
As of October 2012, the ICGC has received commitments from researchers and funding organizations in Asia, Australia, Europe and North America for 47 project teams in 15 jurisdictions to study more than 21,000 tumour genomes. Over 23,000 tumours that meet ICGC requirements for consent have been obtained and over 20,000 samples have been approved by research pathologists as meeting ICGC standards. Raw datasets exist for &gt; 10,000 tumours, including &gt; 1,700 whole genome sequences, &gt; 5,130 exomes, &gt; 9,700 copy number alterations, &gt; 4,900 transcriptomes (RNASeq) and over 6,600 methylomes. Processed data is available via the Data Coordination Centre (http://dcc.icgc.org) based at the Ontario Institute for Cancer Research and is updated bimonthly. The latest data release (Version 10) in October 2012 includes datasets from 33 ICGC members and five additional groups. In total, ICGC data release 10 comprises data from 7,022 cancer genomes.
In the next five years, ICGC will deliver on its initial and new objectives, including 1) sequencing a cumulative number of &gt;25,000 tumour genomes from 50 or more tumour types, 2) improving data quality of ICGC datasets; 3) developing a scalable software infrastructure to support data management and cancer genome research; 4) streamlining data access mechanisms to accelerate usage and downstream discoveries without compromising the need to protect patient confidentiality; 5) coordinating cross-tumour analyses; 6) and training basic and clinician scientists to use ICGC datasets and tools. More information can be found on www.icgc.org
Citation Format: Thomas J. Hudson, Jennifer L. Jennings. International Cancer Genome Consortium (ICGC). [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 2004. doi:10.1158/1538-7445.AM2013-2004
Abstract 2013: Comprehensive genetic characterization of apocrine lesions of the breast.
Authors: Costa Jose L. , Justino Ana , Gomes Madalena , Alvarenga Cesar Augusto , Gerhard Renê , Vranic Semir , Gatalica Zoran , Machado Jose Carlos , Schmitt Fernando 
Published: August 2014

Abstract
Apocrine differentiation occurs in a variety of breast lesions, both benign and malignant. The molecular classification of breast cancer defined an apocrine molecular subtype of breast cancer. In general, apocrine carcinomas do not present clinical behavior distinct from the observed in ductal carcinomas of no special type. However, these carcinomas are frequently triple negative (ER-/PgR-/HER2-) with no targeted therapy and poor prognosis. Still they are unique in the aspect of the expression of a different nuclear receptor - androgen receptor (AR).
In this study we thought to perform a comprehensive genetic/molecular characterization of this type of lesions. For that, a series of 44 apocrine lesions were studied. These comprised 9 apocrine metaplasia, 8 apocrine adenosis, 13 apocrine in situ carcinoma and 18 apocrine invasive carcinoma. Importantly four samples contained different lesions in different stages in close proximity. Immunohistochemistry was performed to evaluate the ER, PgR, HER2 and AR status of these lesions. Genomic DNA was microdissected from FFPE slides and used both to identify chromosomal copy number aberrations using aCGH and to monitor 739 mutations from 46 oncogenes and tumor suppressor genes using the Ion PGM system.
The aCGH study allowed the identification of recurrent chromosomal aberrations. These were rare in benign apocrine lesions, mostly comprised of small gains and deletions, and dramatically increased in malignant lesions up to complete loss and gain of full chromosome arms. Also the analysis of the different lesions within the same sample indicates a putative existence of an apocrine tumor progression. Moreover the profiling of mutational status of the different tumor suppressor/oncogene allowed the identification of mutations that may provide new avenues for the development of new targetable therapeutically options and also corroborated the putative apocrine tumor progression.
The study of apocrine lesions in different differentiation stages allowed a deeper insight on the molecular complexity of these lesions. Although further studies are required to independently validate this work, this study identifies recurrent genomic alteration that may open targeted treatment opportunities that may be used independently or in combination with anti-androgen drugs.
Citation Format: Jose L. Costa, Ana Justino, Madalena Gomes, Cesar Augusto Alvarenga, Renê Gerhard, Semir Vranic, Zoran Gatalica, Jose Carlos Machado, Fernando Schmitt. Comprehensive genetic characterization of apocrine lesions of the breast. [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 2013. doi:10.1158/1538-7445.AM2013-2013