bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2144: An integrated genomic and transcriptomic analysis of human uterine leiomyomas
Authors: Cirilo Priscila D.R , Marchi Fabio A. , Carvalho Alex F. , Pontes Anagloria , Rogatto Silvia R. 
Published: February 2011

Abstract
Uterine leiomyoma (UL) are tumors that arise from the uterine smooth muscle wall. Despite their nonmalignant nature, UL represent a major concern in women's health through their induction of significant morbidity in more than 25% of reproductive-age. The etiology of UL remains unknown. Cytogenetic studies have been identified recurrent aberrations involving the t(12;14); del(7)(q22q32); trisomy 12; and 6p21 rearrangements. The aim of this study was integrate genomic and gene expression microarray data to identify genes with altered function due to genomic instability. DNA and RNA were extracted from 24 UL from women at proliferative (n=14) and secretory (n=10) phase of the menstrual cycle. Normal control RNA was obtained from adjacent myometrium from all cases. Array CGH and gene expression microarray was done using the Human 44K Agilent oligoarrays according to manufacturer's instructions. Data were extracted and flagged with Feature Extraction software (version 10.1.1.1) and processed using Genomic Workbench Standard (version.5.0.14). Non-supervised analysis of gene expression revealed clustering of all cases independent of the phase of menstrual cycle. It was observed a significant correlation between deletion and down expression at 1q32.2-q44 and 7q11.22-q33. Although deletions at 1q and 7q had been described previously as involved in UL, the genes mapped at these regions were poorly studied. These genes are involved in Wnt signaling pathway, induction of apoptosis, transforming growth factor signaling pathway, fumarate hydratase activity, and fibrinolysis. Furthermore, it was observed correlation between amplification and increased gene expression at 11p15.5, 14q32.33, and 16p13.3. These regions harboring genes with function associated with regulation of cell proliferation and regulation of JNK cascade. Our results provide strong circumstantial evidence that different patterns of genomic imbalances contribute to their specific transcriptomic profiles. In the future, new therapies based on these findings can be applied in a subgroup of patients with specific genomic imbalances.
Supported by the FAPESP (07/51643-8) and CNPq (485032/2007-4), Brazil.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2144.
Abstract 215: CSE1L as a potential target to sensitize ovarian cancer cells to cisplatin
Authors: Lorenzato Annalisa , Olivero Martina , Martino Cosimo , Dani Nadia , Musiani Daniele , Calogero Raffaele , Renzo Maria Flavia Di 
Published: February 2011

Abstract
Human ovarian cancer is frequently (70% of cases) at advanced stage at presentation and requires multimodality treatment, consisting of cytoreductive surgery and chemotherapy based on platinum-drugs and taxanes. Patients are initially responsive to this treatment, but, in most cases, experience disease relapse because tumour cells acquire drug resistance.
We demonstrated that the Hepatocyte Growth Factor (HGF) sensitizes to cisplatin (CDDP) and taxol an ovarian carcinoma cell line known to be resistant to platinum drugs: SK-OV-3, leading to an increased cancer cell death at very low drug doses both in vitro and in an animal model (Bardella et al., 2007; Rasola et al., 2004). This was an unexpected finding as HGF and its tyrosine kinase receptor, encoded by the MET oncogene, drives cell proliferation, survival and invasiveness during development and tumorigenesis. We also demonstrated that this effect is mediated by p38MAPK, which overwhelms the concomitant HGF activation of survival pathways, as the expression of a dominant negative form of p38MAPK abrogates the sensitization effect of HGF (Coltella et al., 2006).
Using oligonucleotide microarrays, we studied the transcriptional responses of cell treated with CDDP in the presence or in the absence of HGF, and found that HGF pre-treatment modifies the transcriptional response to CDDP not only in SK-OV-3, but also in NIH-OVCAR-3, and TOV-21G ovarian cancer cells. The up- or down-modulation of the most differentially expressed genes found in common within these cell lines was reverted when the cells expressed a dominant negative form of p38MAPK, upholding once again the involvement of p38MAPK in this phenomenon.
Among the top-ranked differentially expressed genes, which we identified, we focused functional studies on CSE1L/CAS. This gene is a nuclear transporter involved in both proliferation and apoptosis found to be amplified and over-expressed in ovarian cancer. Knocking down of CSE1L/CAS made ovarian cancer cells sensitized to low doses of cisplatin and triggered apoptosis while had no effect on other cancer and normal cell lines.
In conclusion, we show that HGF and CDDP modulate transcription in ovarian cancer cells and that this transcriptional response is involved in apoptosis regulation. We also provide the proof-of-concept that the identified genes might be targeted to either increase the efficacy of chemotherapeutics or to revert chemotherapy resistance.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 215.
Abstract 2151: Molecular screening of CRC from India suggests the existence of non-canonical pathway(s) of tumorigenesis
Authors: Ratheesh R , Viswakalyan K , Chaudhary A K. , Swarnalata G , Srinivasulu M , Lavanya M , Anjayneyulu V , Patnaik S , Vamsy M , Murthy S , Ravikanth K , Sastry R A. , Bashyam M D. 
Published: February 2011

Abstract
A major risk factor for Colorectal Cancer (CRC) is advanced age, with a majority of cases reported in the West being above 60 years of age. However, a significantly high proportion of CRC patients from India belong to a younger age group (less than 50 years) and a majority of them have no family history of cancer. A deregulated Wnt signaling pathway is the hallmark of CRC in the West and has been indicted in 70-80% of older patients. Another significant genetic aberration is Microsatellite Instability (MSI), which may contribute to 15-20% of the cases. In addition, the simultaneous occurrence of Wnt activation and p53 inactivation has been substantiated in a significantly high proportion (about 70%) of CRC cases. Sporadic CRC occurring in the young however has not been subjected to detailed analysis so far. In order to identify important deregulated pathways that drive tumor progression in young patients we have initiated a multipronged comparative study on CRC occurring in the young and older patients from India. Our results have revealed several unique features among Indian CRC patients. Firstly, Wnt activation and p53 inactivation appeared to co-exist in a significantly less proportion of samples (34%), indicating existence of alternate pathway(s) of tumor initiation. Secondly, a significantly low proportion (35%) of young patients appeared to harbor a deregulated Wnt signaling pathway, when compared to older patients (64%). Thirdly, we did not find a significant difference in other variables between the two patient age groups including gender, grade, MSI status, etc. Using array-based Comparative Genomic Hybridization (aCGH) and genome-wide transcript profiling, we identified several copy number alterations (CNA) that may harbor genes important for tumor progression in young patients. A novel amplification located at 17q11.2-21.1 was identified which included genes involved in the MAP kinase pathway. The present study is expected to yield invaluable insights into the molecular basis for sporadic CRC in the young.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2151.
Abstract 2154: Molecular allelo-karyotyping of pulmonary adenocarcinoma using high resolution single nucleotide polymorphism genomic arrays
Authors: Ninomiya Hironori , Kato Motohiro , Takeuchi Kengo , Kanda Hiroaki , Okumura Sakae , Ogawa Seishi , Ishikawa Yuichi 
Published: February 2011

Abstract
Background Lung cancer is the leading cause of cancer death in Japan. Adenocarcinoma is the most common form of lung cancer with poor-prognosis due to late-stage detection and resistance to conventional treatment. The complexity of the genetic alterations confer pulmonary adenocarcinomas with marked patterns of gene expression. It is now critical to unravel the mechanisms which underlie a subset of tumor and they should have a significant impact in selecting patients for targeted therapy. Novel SNP-chip high resolution molecular allelo-karyotyping analysis allows us to examine global DNA copy number changes and allelic loss to evaluate allele-specific gene dosage in cancer cells.
Methods A series of consecutive 111 lung adenocarcinomas, including 10 cases harboring EML4-ALK fusion, were analyzed using Affymetrix GeneChip and our robust algorithm, CNAG/AsCNAR, to perform sensitive analysis of copy number alteration and allelic composition. This robust algorithm also enabled sensitive detection of loss of heterozygosity. Clinicopathological profiles including age, gender, smoking status, WHO histology subtypes, pathological stage and clinical outcome were also examined. Genomic profiles in the selected amplified and deleted regions were obtained.
Results Chromosomal arm gains of 1q, 3q, 5p, 6p, 7p, 8q, 16p and 17q were detected, while frequent loss was found in 1p, 3p, 6q, 8p, 9p, 10q and 17p. Gene alteration profiles of known oncogenes and tumor suppressor genes were obtained with this procedure. Highly amplified regions included TERT (61.3%), MYC (45.9%), EGFR (44.1%), TNFSF6B (44.1%). Homozygous deletion was noted only in 9p23.3 (5.4%, CDKN2A, CDKN2B). Cases with EML4-ALK fusion were found to be less amplified in top 15 selected regions. Lymphatic invasion positive cases revealed distinct genomic profiles compared to negative ones.
Conclusion Global analysis of gene expression using high resolution SNP genomic arrays can provide a broader view of genomic alterations. Genomic amplification and loss profiles differ according to clinicopathological aspects and genomic background.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2154.
Abstract 2158: Loss of heterozygosity at chromosome 3p in ductal and lobular breast carcinomas
Authors: de Oliveira Marcia Maria Costa , Cavalli Luciane R. , Urban Cícero Andrade , de Lima Rubens Silveira , Ribeiro Enilze Maria de Souza Fonseca , Cavalli Iglenir João 
Published: February 2011

Abstract
The two main histological types of infiltrating breast cancer, lobular (ILC) and the more common ductal (IDC) carcinoma are morphologically and clinically distinct revealing different patterns of chromosomal aberrations and gene expression. Loss of heterozygosity (LOH) at chromosome 3p is frequently observed in breast tumors and a whole genome study utilizing a SNP array assay found a significantly higher frequency of LOH on 3p in ductal than lobular tumors. In order to investigate the molecular alterations at 3p associated with these breast cancer subtypes we analyzed LOH in 118 IDC and 18 ILC samples using seven microsatellite markers. Genomic DNA was obtained from frozen tumor tissue and peripheral blood was used as a normal reference. All samples were genotyped on a MegaBace® system and analyzed using Fragment Profiler® Version 2.1 software. Significance was determined using Chi-square test (X2). A significant higher frequency of LOH was observed in IDC (62.7%) when compared with ILC (38.9%) (X2=4.60 P&lt;0.05). When the markers were analyzed separately, LOH at three of them, D3S1307 in 3p26.3, D3S1286 in 3p24.3 and D3S1300 (intragenic FHIT) in 3p14.2, were significantly more frequent in ductal than lobular tumors (X2= 4.66 P&lt;0.05; X2= 3.99 P&lt;0.05 and X2= 5.43 P&lt;0.025, respectively). D3S1307 marker showed the highest frequency of LOH in IDC (47.8%) and associations between loss of this marker and loss of estrogen and progesterone receptors were found in these samples (X2= 4.61 P&lt;0.05 and X2= 4.49 P&lt;0.05, respectively) suggesting that there are genes on this region involved in the control of differentiation of ductal tumors. For lobular tumors, the highest loss (53.3%) was seen for D3S1274 on 3p12.3 (intragenic DUTT1). In addition to confirm previous studies these findings suggest that specific losses on 3p (3p26.3, 3p24.3 and 3p14.2) are more common in IDC when compared with ILC breast tumors.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2158.
Abstract 216: Role of Akt isoforms in chemoresistance of human endometrial carcinoma cells
Authors: Girouard Julie , Asselin Eric 
Published: February 2011

Abstract
AKT (also known as PKB) is a crucial survival kinase that is normally activated by growth factors but is constitutively activated at a high frequency in tumors through oncogenic events affecting its upstream regulation. Since studies have demonstrated that the three Akt isoforms exhibit distinct physiological functions, the aim of this study was to determine the isotype-specific functions for Akt in chemoresistance of endometrial carcinoma cells. In order to determine the role of Akt isoforms, we have stably produced transfectants in which the expression of Akt is downregulated by specific shRNAs for each isoforms using the KLE endometrial carcinoma cell line. This endometrial cell line is known to constitutively express the three Akt isoforms and to highly resist to chemotherapeutic treatment. In this study we have demonstrated that stably downregulation of Akt2 by RNA interference severely sensitized KLE cells to cisplatin and induced apoptosis. Moreover, cisplatin treatment of these cells induced the activation of pro-apoptotic factors such as caspase −3 and −9 but also inhibited the expression of anti-apoptotic factors such as XIAP and bcl-2. Alternatively, we used constitutively active Akt expression vectors for each isoform to produce stable transfectants using the chemosensitive Hec 1A endometrial cancer cell lines in which no Akt activity is detected. Constitutive Akt2 expression leads to increase cisplatin resistance in this stable transfectant. Our findings highlight the contribution of Akt2 isoform in the molecular mechanisms that govern chemoresistance of endometrial carcinoma. Furthermore, Akt isoform-specific transfectants will provide a strong model to determine the involvement of each Akt isoforms in chemoresistance of endometrial carcinoma cells.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 216.
Abstract 2161: Network-based inference of ALK oncogenic signaling in T-cell lymphoproliferative disorders
Authors: Piva Roberto , Pellegrino Elisa , Agnelli Luca , Cantarella Daniela , Ferreri Cristina , Ferracin Manuela , Cuccuru Giuditta , Voena Claudia , Provero Paolo , Negrini Massimo , Cunto Ferdinando Di , Neri Antonino , Medico Enzo , Inghirami Giorgio 
Published: February 2011

Abstract
Anaplastic large cell lymphomas (ALCL) are a subset of T-cell Non-Hodgkin Lymphomas (T-NHL) in which the intracytoplasmic domain of the anaplastic lymphoma kinase (ALK) gene is frequently fused to nucleophosmin (NPM1). It has been previously shown that the transcription factor STAT3 is a major substrate of ALK enzymatic activity and it is strictly required for the growth and survival of ALK-transformed cells.
With the aim to unravel the regulatory network underlying NPM-ALK-mediated transformation and tumor maintenance, we timely dissected the mRNA and miRNA expression signature of ALK-positive ALCL cell lines following ALK or STAT3 silencing. We observed that the majority of ALK-regulated genes were concordantly dependent on STAT3, including known and novel STAT3 target genes. Additional transcription factors (C/EBP beta, LEF1, and others) emerged as STAT3-dependent initiators and master regulators of ALK oncogenic properties in ALCL. However, STAT3 signaling was inconsistent and completely dispensable in non small cell cancer cell lines expressing EML4-ALK fusion proteins, suggesting a T-cell specific STAT3 regulatory network.
Finally, we analyzed the gene expression profiling of 90 systemic peripheral T cell lymphomas, including a set of ALK positive and negative ALCL (n=36). We observed that ALK positive ALCL were significantly clustered in a separate subgroup, characterized by a relevant STAT3 signature. Using prediction analyses, we identified a set of genomic classifiers able to a clearly separate ALK positive and ALK negative ALCL from other T-NHL.
In conclusion we proved that inference of ALK oncogenic transcriptional networks is a powerful tool to identify meaningful signaling molecules that regulate the transition into a pathologic cellular state. Our molecular classification suggests that ALCL may represent a unique entity discernible from other T-NHL, and that a restricted number of genes can be instrumental for clinical stratification and, possibly, to address the therapy of patients.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2161.
Abstract 2163: Global gene expression profiles of the Egyptian hepatocellular carcinoma associated with HCV-Genotype-4
Authors: Zekri Abdel-Rahman N. , Bahnassy Abeer , Hafez Mohamed , Hassan Zeinab 
Published: February 2011

Abstract
Background: Hepatocellular carcinoma (HCC) is a preventable disease rather than a curable one, since there is no well-documented effective treatment modality until now, making the molecular study of this disease mandatory.
Methods: Forty cases of HCV genotype 4-associated HCC patients from Egypt were studied for gene expression profile by 41 K c-DNA microarray.
Result: Out of the 41,000 genes, 958 were differentially expressed; 503 were up regulated (58 genes are involved in 65 different pathways) and 455 were down regulated (49 genes are involved in 59 different pathways). Only 19 pathways were specifically up regulated by 27 genes (ABCB10, ABCG2, RXRA, PRKAB2, IKBKG, ELOVL2, RAF1, ATP6V1A, FLJ21865, GUSB, IL7, EPO, CD1B, FGFR1, PDPK1, KPS6KB1, NOTCH4, CDK7, MNAT1, PRKACB, RXRA, PRKACB, ACCN1, RPS6KB1, BMP8A, SMAD6, CYCLIN E2) and 13 pathways are specifically down regulated by 19 genes (ARHGEF2,WASL, BACE1, A2M, PPP3CA, SLC1A, ITGAV, NRXN2, NCAM1, PER1, PIGX, ST3GAL2, ST3GAL4, DGKQ, ATG5, ENPEP, POLR2B, LTA). Sixty seven genes showed significant difference in their expression between HCC cases with and without cirrhosis. Confirmation of array data by RT-PCR was performed on a subset of genes (PPP3CA [75%], ATG-5 [85%], BACE [62%] which showed down regulation and ABCG2 [90%], RXRA [80%], ELOVL2 [65%], CXR3 [80%]) which showed up regulation.
Conclusion: This is the first study on the global gene expression profile in Egyptian HCC patients associated with HCV-Genotype-4 using the cDNA microarray. The identified genes could provide a panel of new prognostic and diagnostic markers for HCV- associated HCC. Also, our data identified some genes which are related to hepatic encephalopathy like ACCN1, BACE1, apoB, GABA-A AND ATG5 which could play an important role in the cross talk between liver and brain. They could also be used to identify candidate genes for molecular target therapy.
Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2163.
Abstract 2167: Unbiased genomic approaches identify 2 major subclasses of Gastric Cancer with prognostic and predictive value superior to Lauren's and also reveals subtype-specific treatment opportunities
Authors: Tan Iain B. , Lee Julian , Ooi ChiaHuey , Lee MingHui , Boussioutas Alex , Tallez Manuel S. , Ngeow Joanne , Lim KiatHon , So Jimmy , Choo SuPin , Wong WaiKeong , Tan Patrick 
Published: February 2011

Abstract
Introduction: The Lauren's classification of gastric cancer (GC) is widely used with 2 subtypes, intestinal and diffuses having distinct histo-pathological and epidemiological characteristics. Beyond diagnosis, Lauren's classes have limited prognostic and no predictive value.
Methods: We performed gene expression profiling on 37 GC cell lines (GCCL) and 2 independent cohorts of 200 (SG) and 68 (AU) primary GC tumors. We used integrative molecular profiling to discover and characterise molecular subtypes of GC.
Results: Unsupervised hierarchal clustering in GCCLs identified 2 distinct major molecular subtypes termed “G1”and “G2”. Linear models for microarray data (LIMMA) identified 171 distinguishing genes. These were mapped into 2 independent datasets of primary tumors where G1 and G2 subclasses were again identified. G1/G2 subtypes, discovered by unbiased techniques, were found to be related to intestinal and diffuse histology respectively (p &lt; 0.001, chi square test) with 69% concordance. We found G1/G2 but not Lauren's classes to be prognostic (G1 vs G2: median survival: 41 vs 25 mths, HR 1.5, 95% CI: 1.1-2.0 p=0.02; Laurens: p=0.6). Among discordant cases, survival approximated G1/G2 classes rather than Laurens. Survival was superior in “G1 but diffuse” compared to “G2 but intestinal” (median 36 vs 17 months, p=0.08). We next examined the interaction of the subclasses with 5-fluorouracil (5-FU), the only chemotherapy approved for adjuvant treatment of GC. 5 -FU sensitivity as measured by GI-50 in a previous publication was greater in G1 lines (p=0.04). In primary tumours, G1 patients had improved progression free survival with 5FU/RT of borderline significance (test for interaction, p=0.09). We next applied genomic pathway analysis using an approach we previously published (Ooi et al. Plos Genetics 2009). Her2/Ras/ER/PR/BRCA pathways and VEGF/p53/EGFR pathways were deregulated in G1 and G2 subtype respectively suggesting possible subtype specific treatment opportunities.
Conclusion: We describe an unbiased genomic approach that improves upon Lauren's to identify the two major subclasses of gastric cancer. G1/G2 classes have superior prognostic and predictive value and subclass specific therapeutic opportunities.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2167.