bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3764: Genome-wide association study identifies potential susceptibility loci associated with differential response to environmental insults in sporadic Chinese CRC patients
Authors: Cheah Peh Yean , Thean Lai Fun , Koh Woon Puay , Teo Yik Ying , Yuan Jian-Min , Teoh Mei Lin , Li Hui Hua , Wong Yu Hui , Koh Poh Koon 
Published: June 2012

Abstract
To date, genome-wide association studies (GWAS) have identified fourteen SNPs that influence risk of developing colorectal cancer (CRC) in Caucasians. None of these tagging SNPs is within coding region of a candidate gene. Only five of these SNPs were associated with CRC risk in Chinese population. We aimed to perform GWAS to identify new susceptibility loci associated with differential response to environmental insults in sporadic Chinese CRC patients. A total of 1,000 cases (aged 50 years or more) and 1,000 age- and gender-matched healthy controls were genotyped with Affymetrix SNP 6 array, a newer microarray platform which includes the ability to interrogate structural variants. Over 90% of the arrays have call rate of 99% or more. Thirty five arrays with call rate less than 97% and either null QC or negative QC (enzyme) values were replicated. Principal component analysis performed together with 270 HapMap and 92 Singapore Genome Variant Project (SGVP) samples indicate that there is no population substructure. Sixteen outliers were removed. SNPs with call rate less than 99% and minor allelic frequency less than 0.1, and control SNPs not in Hardy-Weinburg equilibrium were filtered. Subsequent quantile-quantile plot shows no evidence of allelic test statistic inflation. Twelve new chromosomal regions with SNPs having -log10 p-values greater than four and good clustering patterns were identified via Manhattan plot. Linkage disequilibrium (LD) analysis was performed to ascertain the LD blocks around these SNPs. SNPs in three chromosomal regions within the vicinity of promising CRC candidate genes were prioritized and currently being validated in a replication panel consisting of another 2,000 cases and controls.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3764. doi:10.1158/1538-7445.AM2011-3764
Abstract 3768: Colorectal cancer risk is not associated with increased levels of homozygosity in a population from Saudi Arabia
Authors: Siraj Abdul K. , Khalak Hanif , Al-Rasheed Maha , Sultana Mehar , Bavi Prashant , Al-Sanea Nasser , Abduljabbar Alaa , Homoud Samar Al , Ashari Luai , Al-Dayel Fouad , Uddin Shahab , Alkuraya Fowzan S. , Al-Kuraya Khawla S. 
Published: June 2012

Abstract
Autozygosity is a term used to denote the presence of two identical haplotypes that are derived from an ancestor shared by both parents, so it essentially represents a special type of homozygosity. Runs of homozygosity (ROH) in the genome is a measure of the extent of autozygosity and is directly correlated with the extent of inbreeding. While the role of ROH in unmasking recessively acting mutations is well established in Mendelian genetics, much less is known about their contribution to more complex disorders such as cancer. Recently, it has been suggested that ROH may contribute to the risk of colorectal cancer (CRC) perhaps through the unmasking of a recessively acting CRC-predisposing mutations in one or more genes. However, this observation could not be replicated. In this study, we examine the role of homozygosity in the CRC risk by asking four specific questions. First, do CRC patients have enrichment for ROH in particular chromosomal regions compared to controls? Second, do CRC patients have longer ROH compared to controls? Third, is there a particular SNP that is more likely to be homozygous in CRC patients compared to controls? And fourth, are CRC patients more inbred than controls? By comparing 48 Saudi CRC patients to 100 ethnically matched controls, all processed on Affy 250SytI SNP Chip platform and analyzed by Partek, we found that the answer is no to all these four questions. We note here that this is the first study to address these questions in an inbred population so the negative results in our study carry more significance than what has been previously reported in the literature. We also note that our subgroup analysis of patients with MSI-positive tumors compared to other groups did not significantly change our results. While these results do not rule out the potential presence of recessively acting CRC-predisposing genes in a small percentage of patients that our relatively small sample size could not capture, they do suggest that such genes are unlikely to account for the disturbingly high incidence of CRC in our consanguineous population and that future research should consider other mechanisms.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3768. doi:10.1158/1538-7445.AM2011-3768
Abstract 3791: MAPK p38 is the link between autophagy and lipid metabolism in colorectal cancer cells
Authors: Salomé Paillas 
Published: June 2012

Abstract
Autophagy is an intracellular degradation system that delivers cytoplasmic constituents to the lysosome. Recent progress has demonstrated that autophagy plays a wide variety of physiological and pathophysiological roles, notably in cancer.
We have showed previously, that the p38 pathway was involved in Irinotecan sensitivity of colon cancer cells p53WT.
p38 being involved in the induction of autophagy we wanted to determine its role in the processes of autophagy in presence and in absence of p53 in colorectal cancer cells.
Our results show that the overexpression of the constitutively active p38alpha isoform in HCT116 p53KO cells leads to a massive autophagy, accompanied with a block in G2 / M. The induction of autophagy in this context doesn't leads to the cellular death but rather to survival. The autophagy induction by p38 overexpression in HCT116 was weaker, indicating that the lack of p53 increase p38 role in autophagy induction.
Furthermore, we have shown that autophagy induced by p38 comes along with an increase of the lipid metabolism by activating a key enzyme of the synthesis of fatty acids.
We demonstrate here, that the role of p38 in the induction of autophagy depends on the presence of p53 and that p38 would be the link between the increase of the lipid metabolism and the induction of autophagy that lead to survival.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3791. doi:10.1158/1538-7445.AM2011-3791
Abstract 3800: HES6 gene is a strong glioma biomarker and a key transcriptional regulator needed for cancer cell growth
Authors: Haapa-Paananen Saija M. , Kiviluoto Santeri , Waltari Marika , Puputti Marjut , Mpindi John-Patrick , Kohonen Pekka , Tynninen Olli , Haapasalo Hannu , Joensuu Heikki , Perälä Merja , Kallioniemi Olli 
Published: June 2012

Abstract
Malignant glioma is the most common brain tumor with 16,000 individuals diagnosed annually in the United States. We performed a systematic large-scale transcriptomics data mining study of 9,783 Affymetrix samples from the GeneSapiens database (www.genesapiens.org) to systematically identify genes that are most glioma-specific. We searched for genes that were highly expressed in 322 glioblastoma multiforme tissue samples and 66 anaplastic astrocytomas as compared to 425 samples from histologically normal central nervous system. Transcription cofactor HES6 (Hairy and Enhancer of Split 6) emerged as one of the most glioma-specific genes. Immunostaining of a tissue microarray showed HES6 expression in 335 (98.8%) out of the 339 glioma samples. HES6 was also expressed in endothelial cells in normal and glioma tissues. Recurrent grade 2 astrocytomas and grade 2-3 oligodendrogliomas showed higher levels of HES6 immunoreactivity than the corresponding primary tumors. Functional studies implied a critical role for HES6 in supporting survival of glioma cells, as evidenced by reduction of cancer cell proliferation and induction of Caspase 3/7 activity after HES6 silencing in A172 and LN405 cells. The biological role and consequences of HES6 silencing and overexpression was explored with genome-wide analyses, which implicated a role for HES6 in p53, c-myc, and NF-κB transcriptional networks. We conclude that HES6 has a critical role in sustaining glioma cell growth, survival, migration and possibly angiogenesis. HES6 is a potential therapeutic target and biomarker for glioma.
This work was supported by funding under the 6th FP of the European Union, Project RIGHT (LSHB-CT-2004-005276), and the Academy of Finland.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3800. doi:10.1158/1538-7445.AM2011-3800
Abstract 3805: Novel chemosensitive single-nucleotide polymorphism markers to targeted regimens in metastatic colorectal cancer
Authors: Kim Jin Cheon , Kim Seon Young , Cho Dong Hyung , Ha Ye Jin , Choi Eun Young , Kim Chan Wook , Roh Seon Ae , Kim Tae Won , Ju Hyoung Seok , Kim Yong Sung 
Published: June 2012

Abstract
Purpose: Methods for predicting individual responsiveness to targeted chemotherapy are urgently needed, considering the frequent resistance and extremely high cost of such therapies.
Experimental Design: A chemosensitive single-nucleotide polymorphism (SNP) discovery schema is presented that utilizes genome-wide SNP screening with a human SNP array, an in vitro chemosensitivity assay in 118 colorectal cancers, clinical association analysis in 98 patients who had received metastatic chemotherapy, and biological utility assessment using cell viability assays of transfected colorectal cancer (CRC) cells.
Results: Eleven SNPs related to bevacizumab and cetuximab sensitivity were initially chosen during screening. Response rates and survival periods revealed that patients carrying specific alleles of the SNPs ANXA11 rs1049550, LINS1 rs11247226, or ITGA3 rs2230392 were chemosensitive to bevacizumab regimens, and patients with DFNB31 rs2274159, LIFR rs3729740, or ISX rs361863 were chemosensitive to cetuximab regimens. Cytotoxicity analyses using MTT and caspase-3 assays showed that all RKO and HCT116 CRC clones transfected with the reference alleles of LIFR rs3729740 and ISX rs361863 (G and C, respectively) were more sensitive to cetuximab regimens than those transfected with the substitution alleles.
Conclusions: Chemosensitive SNP markers were identified using a novel three-step process. The chemosensitive markers LIFR rs3729740 and ISX rs361863 will hopefully predict responsive patients to cetuximab regimens, although further validation is needed in large cohorts.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3805. doi:10.1158/1538-7445.AM2011-3805
Abstract 381: Light-absorbing nanoparticles induce cell death in esophageal cancer cells
Authors: Li Yan , Gobin Andre M. , Dryden Gerald W , Xiao Deyi , Zhang Guandong , Martin Robert C. 
Published: June 2012

Abstract
Background Light-absorbing nanoparticles that are nontoxic to biological tissue possess the potential for targeted killing of cancer cells while causing minimal collateral damage to adjacent healthy tissue. Gold nanoparticles with near infrared (nIR)-absorbing light properties are ideal for this application. Aim: This study is to investigate the photo-thermal ablation effect of nIR-absorbing gold nanoparticles coated with a natural polymer (chitosan) on esophageal cancer cells as well as benign cells. Methods: Three esophageal cell lines used are human squamous esophageal epithelium cell line (Het-1A), Barrett's epithelium cell line (BAR-T), and the esophageal adenocarcinoma cell line (OE-19). Furthermore, the uptake of gold nanoparticles in the benign esophageal tissue and the response to laser exposure was also valuated in a rat esophagoduodenal anastomosis (EDA) model. Three cell lines were treated with gold nanoparticles (OD=25) then exposed to laser at a wavelength of 817 nm and power density of 3W/cm2 for 3 min. The esophageal mucosa of rats was sprayed with gold nanoparticles 24 hours befor laser application. After treatment, the rats were exposed to laser at a wavelength of 817 nm and power density of 4.15W/cm2 for 3 min. The loading of gold nanoparticles was detected by silver staining. Results: The most OE-19 cells loaded with gold nanoparticles and were completely ablated after nIR light exposure. However, most Het-1A cells and BAR-T cells didn't load on any gold nanoparticles, and they remained viable after nIR light exposure. Normal esophageal epithelium and Barrett's mateplastic epithelium show low affinity to gold nanoparticles, however, the focal region with more loaded gold nanoparticles was ablated after nIR light exposure. Conclusion: 1) Chitosan coated gold nanoparticles undergo targeted uptake by OE-19 cells, with a much higher affinity compared to benign cells. 2) Photo-thermo-ablation by nIR light exposure causes a directed cancer cell-killing effect based on preferential gold nanoparticle uptake. 3) Further study is ongoing to investigate methods of enhancing peak uptake of gold nanoparticles in the EDA rat model, to provide an optimal model for laser ablation of esophageal cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 381. doi:10.1158/1538-7445.AM2011-381
Abstract 3819: Matrix metalloproteinase-1 (MMP1) is an important marker of oral squamous cell carcinoma
Authors: Stott-Miller Marni , Houck John , Lohavanichbutr Pawadee , Schwartz Stephen M. , Upton Melissa P. , Chen Chu 
Published: June 2012

Abstract
The matrix metalloproteinase genes have frequently been identified as important in cancer development and progression, including in oral squamous cell carcinoma (OSCC). These proteases are believed to cause degradation of the extracellular matrix and basement membranes and therefore to play a key role in tumor metastasis, cell migration, cancer cell growth, and angiogenesis. We compared MMP1 expression levels in primary OSCC (n=119) with expression levels in normal oral epithelium from control subjects (n=35), as measured by Affymetrix U133 2.0 Plus GeneChip arrays, adjusting for age and sex. MMP1 was expressed more than 200-fold higher in OSCC compared with normal control epithelium. qRT-PCR results on 30 of the cases and 22 of the controls confirmed the substantial differential expression of MMP1, with a difference in mean threshold cycle (Ct) value for cases versus controls of 9.85 (95% CI, 8.74-10.97, p&lt;0.001). In an independent testing set of 48 OSCC tissue samples and 10 control samples, MMP1 had exceptional discriminatory power to separate cases from controls (AUC=100%). This result was further validated in an external data set from Gene Expression Omnibus (GEO; GSE6791) of 42 OSCC cases and 14 controls (AUC=98.4%; 95% CI, 95.6%-100%). The mean of the log2 MMP1 expression levels on the Affymetrix arrays for 45 normal oral epithelium was 3.49 (95% CI, 3.21-3.78), 17 dysplasia tissue samples had mean expression of 6.69 (95% CI, 5.21-8.17), 108 stage T1/T2 cases had a mean of 10.93 (95% CI,10.49-11.37), and the mean of 57 stage T3/T4 cases was 11.38 (95% CI,10.81-11.95). These results suggest that MMP1 is increasingly dysregulated during the process of oral carcinogenesis. The capacity of MMP1 to identify OSCC provides support for further investigation into this enzyme as a potential marker for OSCC development and/or progression.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3819. doi:10.1158/1538-7445.AM2011-3819
Abstract 385: Monocyte chemoattractant protein-1 (MCP-1)/CCL2 produced by non-tumor cells in tumor stroma promotes lung metastasis of 4T1 murine breast cancer cells
Authors: Yoshimura Teizo , Zack Howard O. M. , Matsukawa Akihiro , Chen Keqiang , Liu Ying , Wang Ji Ming , Oppenheim Joost J. 
Published: June 2012

Abstract
MCP-1 is a chemokine that plays an important role in the initiation and progression of cancer by attracting immunosuppressive macrophages. A wide variety of tumor cell lines produce MCP-1 in vitro; thus, tumor cells are considered to be the main source of this chemokine. In the present study, we examined whether MCP-1 deficiency in non-tumor cells present in tumor stroma affects the growth and metastasis of the 4T1 mouse breast cancer cells implanted into the mammary pad of wild-type (WT) or MCP-1-deficient mice. Tumors grew at a similar rate in both WT and MCP-1-deficient mice at the injected sites; however, the lung metastases were markedly reduced in MCP-1-deficient mice. Serum MCP-1 levels increased after 4T1 cell implantation in WT, but not in MCP-1-deficient mice. High levels of MCP-1 mRNA were detected in the mammary tumors of WT, but not of MCP-1-deficient mice, indicating that tumor cells were not the main source of MCP-1. In tumors of MCP-1-deficient mice, the infiltration of macrophages was reduced and the expression of cytokines, including IFN-γ, IL-4, IL-10 and IL-13, was elevated. Transplantation of MCP-1-deficient bone marrow cells into WT mice did not affect the number of lung metastasis, whereas transplantation of WT bone marrow cells into MCP-1-deficient mice significantly increased the lung metastasis. Finally, culture supernatants of 4T1 cells induced MCP-1 production in inflammatory macrophages. These results suggest that MCP-1 produced by non-tumor cells in tumor stroma, both bone marrow-derived and non-bone marrow-derived, facilitates lung metastasis of 4T1 cells by recruiting immunosuppressive macrophages. Thus, the inhibition of MCP-1 may be useful to reduce lung metastasis of breast cancer cells.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 385. doi:10.1158/1538-7445.AM2011-385
Abstract 3852: Identification and functional characterization of T-cell lymphoma invasion and metastasis 2 (TIAM2) in neuronal cells
Authors: Chen Jia-Shing , Sun H. Sunny 
Published: June 2012

Abstract
T-Cell Lymphoma Invasion and Metastasis 2 (TIAM2) gene was identified as the homolog for human TIAM1 gene, a Rac-specific guanine nucleotide exchange factor (GEF), and classified as a member of TIAM GEF subfamily. Although functions of TIAM family proteins have been extensively studied, the characteristics of human TIAM2 remain largely unknown. In this study we systematically investigate the cellular function of TIAM2. Two mRNA isoforms of TIAM2, TIAM2S and TIAM2L, were detected and showed distinct expression patterns in various human tissues. Although both mRNAs are highly expressed in many human tissues, no TIAM2L protein can be detected in any of the examined human tissues and cell lines. In addition, TIAM2S protein only expressed in neuron of restricted regions in the human brain. Overexpression of TIAM2S-GFP fusion protein revealed a cytosolic distribution in both HeLa and NIH3T3 cells. Using LC/MS/MS and enzymatic analysis, TIAM2S was shown to be an O-linked glycoprotein. As transiently transfected TIAM2S-fusion protein neither translocate onto the cell membrane, nor exhibit GEF activity to RhoGTPases in vivo, these data suggested human TIAM2S is not a classical GEF and its functional role in normal brain may differ from other TIAM members.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3852. doi:10.1158/1538-7445.AM2011-3852
Abstract 3859: Defining groupings of oropharyngeal squamous cell carcinomas by expression patterns of human papillomavirus oncogenes
Authors: Laborde Rebecca R. , Olsen Steven D. , Wang Vivian , Garcia Joaquin J. , Graham Rondell , Berres Michael W. , Halling Geoffrey C. , Olsen Kerry D. , Moore Eric J. , Kasperbauer Jan L. , Tombers Nicole D. , Smith David I. 
Published: June 2012

Abstract
There is considerable clinical interest in the role that human papillomavirus (HPV) plays in the development of oropharyngeal cancers. A variety of assays are currently available to stratify patients based on HPV status prior to treatment. The most frequently utilized are PCR and In Situ hybridization (ISH) to detect the presence of HPV DNA sequences. The increasing clinical interest in determining HPV patient status relates to compelling evidence that a subset of patients with HPV positive tumors have better clinical outcomes. Evidence also suggests that patients with HPV positive tumors should be further divided into groupings based on levels of viral activity and that this may represent additional clinical information necessary to develop appropriate treatment plans. The most frequently applied assay to identify HPV activity in a patient sample is to detect the over-expression of the surrogate protein marker p16 by Immunohistochemisty (IHC), which has been shown to increase expression in response to HPV active infections in oropharyngeal cancer. An alternative technique to quantitatively detect the presence and level of transcriptional activity of HPV in tissue samples is to measure the expression of oncogenes E6 and E7. We have analyzed the fresh frozen tissue samples corresponding to matched tumor, normal and metastatic patient tissues using a quantitative PCR (qPCR) approach to determine the expression of HPV oncogenes and p16 gene expression. We observed that there are three groups of oropharyngeal tumors when grouped by HPV16 E6 and E7 gene expression. The first are the most rare and are tumors that contain no HPV sequences or expression of the E6 and E7 ocogenes. The second are tumors that contain HPV DNA sequences but very low expression of E6 or E7 and the third are tumors that contain HPV DNA sequence and robust expression of E6 and E7. Additionally, we found variable correlation between HPV16 E6 and E7 expression and p16 gene expression, suggesting that factors other than HPV oncogene expression may influence the expression of p16. Our results would indicate that the best assays for quantifying the activity of an HPV infection in oropharyngeal cancers would be those optimized to accurately measure either E6 and E7 transcripts or their protein products directly out of paraffin-embedded tissues.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3859. doi:10.1158/1538-7445.AM2011-3859