bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4811: Compression-induced cell distension stimulates coordinated migration of mammary carcinoma cells
Authors: Tse Janet M. , Cheng Gang , Tyrrell James A. , Wilcox-Adelman Sarah A. , Jain Rakesh K. , Munn Lance L. 
Published: February 2011

Abstract
Uncontrolled cell proliferation of a solid tumor in a confined space not only creates oxidative stress (hypoxia), but also generates mechanical compressive stress, which can influence the tumor cells and modify their interactions with neighboring cells and the extracellular matrix. Little is known about how such compressive stress affects cancer progression. Here we show, for the first time, that externally-applied compressive stress results in faster migration of mammary carcinoma cells. Compression induces migration of mammary carcinoma cells in a coordinated sheet, initiated by “leader cells” - single cells at the leading edge of the sheet, extending long filopodia. The formation of leader cells is dependent on the geometry of association with neighboring cells, but the frequency of leader-cell formation - and sheet migration speed - is increased by applying compression perpendicular to the sheet. Accompanied by redistribution of fibronectin deposition, applied compression enhances cell-matrix adhesion and stabilizes cell distension independent of actomyosin contractile machinery. Our results suggest that mechanical stress accumulated during tumor growth is sufficient to enhance cell-substrate adhesion and stimulate cancer cell migration. This mechanism opens the door to a new class of targets for blocking mechanical stress pathways.
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 4811.
Abstract 4812: Collagen regulation of Snail expression in pancreatic cancer involves TGF-β1 signaling
Authors: Shields Mario A. , Dangi-Garimella Surabhi , Krantz Seth , Bentrem David J. , Munshi Hidayatullah G. 
Published: February 2011

Abstract
Pancreatic cancer, the fourth leading cause of cancer death in the U.S., is associated with pronounced desmoplastic reaction; however, the role of this collagen-rich fibrotic reaction in pancreatic cancer progression is poorly understood. Previously, we had shown that the collagen increased expression of the key proteinase membrane type 1-matrix metalloproteinase (MT1-MMP). Now we show that collagen can also increase expression of the zinc-finger transcription factor Snail to enhance pancreatic cancer invasion. Relative to cells grown on tissue culture plastic, PDAC cells grown in 3D collagen gels induced Snail. As we had previously published that TGF-β1 increases Snail levels, we examined the contribution of TGF-β1 signaling to collagen-induced Snail expression. Inhibiting TGF-β1 signaling with siRNA against TGF-β1 receptor type I (TbRI) or with a highly specific inhibitor of TbRI kinase activity attenuated the effect of collagen on Snail levels. To further examine the role of Snail in PDAC progression, we generated Snail-inducible PDAC cells lines. Expression of Snail in PDAC cells grown in 3D collagen gels enhanced invasion, which was blocked in the presence of the MMP inhibitor GM6001. Overexpression of Snail in PDAC cells increased MT1-MMP, while siRNA against Snail decreased MT1-MMP and also attenuated collagen-induced MT1-MMP expression. Snail expression of MT1-MMP requires ERK1/2 signaling and blocking ERK1/2 phosphorylation inhibited Snail-induced invasion in 3D collagen gels. To provide in vivo support for our findings that Snail can regulate MT1-MMP, we examined the expression of Snail and MT1-MMP in human PDAC tumors and found a statistically significant positive correlation between MT1-MMP and Snail in these tumors. Overall, our data demonstrate that collagen-rich milieu can increase the expression of Snail, and suggests that the desmoplastic reaction actively contributes to PDAC progression.
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 4812.
Abstract 4824: Little evidence of human papillomavirus in lung tumor tissue
Authors: Koshiol Jill , Rotunno Melissa , Gillison Maura , van Doorn Leen-Jan , Tarantini Letizia , Song Hebin , Quint Wim , Struijk Linda , Goldstein Alisa , Chaturvedi Anil , Hildesheim Allan , Taylor Philip , Wacholder Sholom , Bertazzi Pier Alberto , Landi Maria Teresa , Caporaso Neil 
Published: February 2011

Abstract
Background: Lung cancer kills over one million people worldwide each year. Human papillomavirus (HPV) has been proposed as a potential cause. Over 50 studies have evaluated HPV in lung tumor tissue over the last 20 years with mixed findings, but most were severely underpowered or had other methodological limitations. While several HPV-associated cancers have been identified (e.g., cervical, tonsillar), the role of HPV in lung carcinogenesis remains controversial.
Methods: We tested 450 lung cancer cases in the Environment And Genetics in Lung cancer Etiology (EAGLE) Italian population-based, case control study for HPV DNA. DNA was extracted from ethanol or formalin-fixed, paraffin-embedded tumor tissue under strict PCR clean conditions and was evaluated for HPV16 and 18 by type-specific, real-time PCR targeted to the E6 or E7 gene. The number of cell equivalents evaluable in these reactions was estimated by real-time PCR targeted to the human ERV3 gene. DNA purity was assessed by standard spectrophotometry (260/280 ratio).
Results: 79.6% (n=358) of the 450 cases were male, 48.9% (n=220) were current smokers, 44.0% (n=198) were former smokers, 6.7% (n=30) were never smokers, and 0.4% (n=2) had unknown smoking status. 399 of 450 cases (88.67%) met quality indices for DNA quantity (at least 100 evaluable cell equivalents) and quality (260/280 ratio of 1.5 to 2.2). Of these, 398 (99.75%, 95% confidence interval: 98.61%-99.99%) were negative for HPV16 and 18. One case, a female former smoker with adenocarcinoma, was positive for HPV16 at low copy number (0.4 per 1000 cell equivalents). We are currently evaluating a subset of cases (n=100) for a broad spectrum of HPV types by PCR with SPF10 primers and a cocktail of conservative probes recognizing at least 54 mucosal HPV genotypes in a microtiter plate format (DEIA). To date no HPV has been detected in the 30 cases tested.
Conclusions: Using extensive laboratory efforts to avoid DNA contamination and sensitive HPV DNA detection assays, we found no evidence to support a role for HPV in lung cancer in a representative Western population. Our results provide the strongest evidence to date to rule out a role for HPV in lung carcinogenesis.
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 4824.
Abstract 4827: A novel FGFR2 haplotype is associated with increased risk of breast cancer in African American women
Authors: Shetty Priya B. , Barnholtz-Sloan Jill S. , Guan Xiaowei , Nyante Sarah J. , Millikan Robert C. 
Published: February 2011

Abstract
Objectives: The objective of this study was to identify new and validate known SNPs and haplotypes in FGFR2 associated with risk of breast cancer in African American women.
Methods: Study participants were from the Carolina Breast Cancer Study, a population-based case-control study conducted in North Carolina. Cases and controls were frequency-matched on age and race. 1536 SNPs and 158 AIMs (ancestry informative markers) were genotyped with the Illumina GoldenGate assay. 89% of the SNP panel and 91% of the AIMs passed quality control. Associations between single SNPs and breast cancer were examined using logistic regression in SAS 9.2, and linkage disequilibrium (LD) between SNPs was tested with SAS/Genetics. Haplotypes were constructed and evaluated for association with breast cancer using generalized linear models as implemented in Haplo. stats. Statistical analyses were conducted on the whole dataset and stratified by race and age at diagnosis. 10 single SNPs in FGFR2 were analyzed. Of these 10 SNPs, rs11200014, rs2981579, rs1219648 and rs2420946 were further analyzed in haplotype analysis in order to compare our results with previous studies. As African Americans were over-sampled, all analyses were adjusted to account for study design.
Results: There were 3748 participants in the study; 742 cases (37.6% of cases) and 658 controls (37.0% of controls) were African American, and 1230 cases and 1118 controls were non-African American. 9 SNPs in all women, 9 SNPs in older women (&gt; 50 years at diagnosis), 7 SNPs in younger women (&lt; 50 years at diagnosis), 8 SNPs in African Americans and 9 SNPs in non-African Americans were associated with increased risk of breast cancer after adjusting for European ancestry and/or race and age. In all subjects, the ATGT, GTGT and GTAT haplotypes were associated with increased odds of breast cancer after adjusting for age, race and ancestry. In African American women, the GTGT haplotype was associated with significant increased risk of breast cancer while the ATGT haplotype was associated with increased risk in non-African American women. Interestingly, the GTGT haplotype was also found to be associated with increased risk of breast cancer among women aged &lt;50 years old at diagnosis.
Conclusions: The GTGT haplotype in FGFR2 is a newly discovered haplotype that is associated with increased risk of breast cancer in African American and younger women. Previous studies have primarily focused on post-menopausal, European American women, and these results highlight the need to conduct genetic epidemiology studies in a variety of racial/ethnic populations.
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 4827.
Abstract 4829: Plasma coenzyme Q10 levels and postmenopausal breast cancer risk: The Multiethnic Cohort Study
Authors: Chai Weiwen , Caberto Christian P. , Shvetsov Yurii B. , Wilkens Lynne R. , Franke Adrian A. , Cooney Robert V. , Marchand Loic Le , Henderson Brian E. , Kolonel Laurence N. , Goodman Marc T. 
Published: February 2011

Abstract
Background: Coenzyme Q10 (CoQ10) is a component of the mitochondrial electron transport chain and is considered an important cellular antioxidant. Lower circulating CoQ10 levels are reported in patients with breast cancer, but epidemiologic evidence from large prospective studies is lacking. We examined the association of plasma CoQ10 levels with postmenopausal breast cancer risk in prospectively collected blood samples.
Methods: Plasma levels of total CoQ10 were measured by HPLC with UV detection after precolumn coulometric oxidation among 160 incident postmenopausal breast cancer cases and 289 controls in the Multiethnic Cohort Study. Cases and controls were individually-matched on age, sex, ethnicity, study location (Hawaii or California), hormone replacement therapy use, date/time of collection and hours of fasting. Conditional logistic regression was used to compute odds ratios (ORs) and 95% confidence intervals (CIs).
Results: Plasma CoQ10 levels were positively associated with breast cancer risk among postmenopausal women in the current study. The OR for the highest versus the lowest tertile was 1.6 (95% CI: 1.0 - 2.6; P = 0.05). The strongest association was observed for postmenopausal women under age 60 (OR for the highest versus the lowest tertile: 3.9; 95% CI: 1.1 - 14.0). Results were similar after adjusting for breast cancer risk factors.
Conclusions: Higher CoQ10 levels in postmenopausal women are associated with increased breast cancer risk in this multiethnic population. Future studies are needed to define the origin of circulating CoQ10, its physiological meaning, and potential role in cancer etiology and progression.
This work was supported by NIH Grants CA132149, CA33619. One of the authors (WC) was supported by NIH Training Grant CA90956.
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 4829.
Abstract 483: Genome-wide analysis identify molecular regulators of metastasis
Authors: Ryu Seongho , Mittal Vivek 
Published: February 2011

Abstract
Metastasis of primary tumors to distant target organs such as the lungs is a major factor contributing to cancer-related mortality. To identify key miRNAs of metastasis we have performed high throughput Solexa sequencing on tumors harvested form variety of metastatic tumor models. In this study, we will present the identification of novel candidates of microRNAs and their target genes. We also validate their biological properties both in vitro and in vivo models of breast and prostate cancer metastasis. Since relatively little is known about regulation system of miRNAs that governs metastasis, the identification and validation of upstream factors will be of great benefit in understanding metastasis regulation. We performed a meta-analysis combines miRNA expression profiles and genome-wide epigenetic modification signatures obtained by using ChIP-SEQ technique. We will also discuss potential clinical significance of key candidates identified in this screen.
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 483.
Abstract 484: Treatment strategy to reverse osteolytic breast cancer metastasis using osteoblasts in a murine xenograft model
Authors: Bodenstine Thomas M. , Beck Benjamin H. , Welch Danny R. 
Published: February 2011

Abstract
The most common site of breast cancer metastasis is bone. The majority of these metastases are osteolytic, characterized by an increase in bone degradation via an upregulation of osteoclast activity. These effects lead to complications including fracture, contractile pain and hypercalcemia, significantly reducing the quality of life in these patients. The role of bone forming osteoblasts at sites of osteolytic lesions is less understood. We have recently shown that breast cancer cells are capable of inducing apoptosis of osteoblasts in vitro as well as in vivo using murine xenograft models. This effect would further exacerbate osteolytic disease, and may explain why treatment strategies capable of inhibiting osteolysis (bisphosphonates) are not capable of repairing lost bone. We hypothesize that modulating the number of osteoblasts at sites of osteolytic metastases, may aid in the repair of resorbed bone. To provide proof-of-principle evidence, we have engineered the murine pre-osteoblast cell line, MC3T3-E1, to overexpress Bcl2, conferring resistance to apoptosis. These cells will be used with an in vivo model of osteolysis using GFP-labeled breast cancer cells previously reported by our laboratory. Apoptosis resistant MC3T3-E1 will be injected into bone both before, and after induction of osteolysis and rates of bone resorption and repair will be measured. The results of this project will provide the first in vivo evidence that restoration of osteoblasts at sites of osteolytic metastases can aid in the repair of lost bone and will test for the first time, experimental manipulation of osteoblast number and function in osteolytic breast cancer metastasis.
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 484.
Abstract 4860: Pan-HDAC inhibitor treatment sensitizes breast cancer cells to autophagy inhibitor 2-phenylethynesulfonamide: Molecular mechanism
Authors: Rao Rekha , Nalluri Srilatha , Fiskus Warren , Mudunuru Uma , Bhalla Kapil N. 
Published: February 2011

Abstract
The stress phenotype of transformed cells is associated with increased levels of heat shock proteins (hsp) and autophagy to avoid cell death. Autophagy is a conserved catabolic pathway in which cytoplasmic macromolecules and organelles are sequestered in autophagosomes, which fuse with lysosomes for protein degradation and amino acid recycling. The molecular cascade initiating autophagosome formation is triggered by a lipid kinase (PI3KC3) signaling complex (Vps34, Vps15, ATG6 and ATG14) that mediates phagophore nucleation. We have previously reported that treatment with panobinostat (PS), a pan-histone deacetylase (HDAC) inhibitor induced hyperacetylation of hsp70 and hsp90. In the present study we demonstrate that treatment of MB231 cells with PS increased the association of hyperacetylated hsp70 with the PI3KC3 VPS34, ATG6 (Beclin-1) and KAP1 (an E3 ligase for sumoylation). PS treatment also induced the levels of ATG7, ATG5 and LC3-II (a phosphatidylethanolamine conjugated ATG8) in MB-231 cells. Treatment with 2-phenylethynesulfonamide (PES), a small molecule inhibitor of hsp70 function resulted in the abrogation of PS-induced interaction of hsp70 with hsp40, VPS34 and (the lysosome-associated membrane protein A (LAMP-2A), a protein involved in chaperone mediated autophagy. Consequently, as compared to treatment with each agent alone, co-treatment with PS and PES resulted in significantly more cell death in MB-231 and SUM159PT cells (p &lt; 0.05). Co-treatment with PS also significantly enhanced lethality of breast cancer MB-231 and MCF-7 cells due to autophagy inhibitor 3-methyl-adenosine (3-MA, inhibitor of Vps34), or hydroxychloroquine (inhibitor of lysosome acidification). In orthotopically implanted MB-231 xenografts in the mammary fat pads of NOD/SCID mice, tumor size increase to 100, 200, 500, 1000 and 2000 cu mm demonstrated tumor size-dependent increase in the intracellular levels of hsp90 and hsp70, hyperacetylated hsp70, ATG7, ATG5, Beclin1 as well as LC3-II. These in vivo findings suggest that as breast tumors grow they exhibit the stress-phenotype involving proteotoxic stress and autophagy. Our findings demonstrate the combination therapy with PS and autophagy inhibitor, which eliminates breast cancer cells with stress phenotype including autophagy, may be especially effective against established and enlarging breast cancers.
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 4860.
Abstract 4861: The role of histone deacetylases (HDACs) in XPC gene silencing and bladder cancer development
Authors: Wang Gan , Wang Lily , Xu Xiaoxin S. 
Published: February 2011

Abstract
The role of histone deacetylases (HDACs) in XPC gene silencing and bladder cancer development
Xiaoxin S. Xu, Le Wang, and Gan Wang
Institute of Environmental Health Sciences, Wayne State University, 259 Mack Ave., Detroit, MI 48202
Bladder cancer is one of the most common malignancies and causes hundreds thousands of death worldwide each year. Bladder cancer is strongly associated with exposure to environmental carcinogens. It is believed that DNA damage generated by environmental carcinogens and their metabolites causes development of bladder cancer. Nucleotide excision repair (NER) is the major DNA repair pathway for repairing bulk DNA damage generated by most environmental carcinogens and XPC is a DNA damage recognition protein required for initiation of the NER process. Recent studies demonstrate reduced levels of XPC protein in tumors for a majority of bladder cancer patients. In this work we investigated the role of histone deacetylases (HDACs) in XPC gene silencing and bladder cancer development. The results of our HDAC inhibitor study revealed that the treatment of HTB4 and HTB9 bladder cancer cells with HDAC inhibitor valproic acid (VPA) caused an increase in transcription of the XPC gene in these cells. The results of our chromatin immunoprecipitation (ChIP) studies indicated that the VPA treatment caused increased bindings of both CREB1 and Sp1 transcription factors at the promoter of XPC gene for both HTB4 and HTB9 cells. The results of our immunohistochemistry (IHC) staining studies further revealed a strong correlation between the presence of HDAC4 and the occurrence of bladder tumors. In addition, the results of our caspase 3 activation studies demonstrated that the prior treatment with VPA increased the anticancer drug cisplatin-induced activation of caspase 3 in both HTB4 and HTB9 cells. All these results suggest that the HDACs negatively regulate transcription of the XPC gene in bladder cancer cells and contribute to the development of bladder cancer.
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 4861.
Abstract 4869: Transcriptional upregulation of histone deacetylase 2 promotes Myc-induced oncogenic effects
Authors: Marshall Glenn M. , Gherardi Samuele , Xu Ning , Neiron Zillan , Trahair Toby , Scarlett Christopher , Chang David K. , Liu Pei Y. , Jankowski Kacper , Iraci Nunzio , Haber Michelle , Norris Murray D. , Stossi Fabio , Katzenellenbogen Benita S. , Biankin Andrew V. , Perini Giovanni , Liu Tao 
Published: February 2011

Abstract
Myc oncoproteins induce cancer cell proliferation by transcriptional modulation. Histone deacetylases (HDACs) enhance cancer cell proliferation and survival, in part, by effects on tumour suppressor gene transcription, and thus HDAC inhibitors are among the most promising new classes of anticancer drugs. Here we show that N-Myc and c-Myc up-regulated HDAC2 gene expression in neuroblastoma and pancreatic cancer cells respectively, which contributed to N-Myc- and c-Myc-induced cell proliferation. Affymetrix microarray revealed that a subset of genes, including cyclin G2 (CCNG2), was commonly repressed by N-Myc and HDAC2 in neuroblastoma cells. PCR analysis confirmed that CCNG2 gene transcription was commonly repressed by N-Myc and HDAC2 in neuroblastoma cells and by c-Myc and HDAC2 in pancreatic cancer cells, and could be reactivated by HDAC inhibitors. BrdU incorporation assays demonstrated that transcriptional repression of CCNG2 was, in part, responsible for N-Myc-, c-Myc and HDAC2-induced cell proliferation. Dual cross-linking chromatin immunoprecipitation and protein co-immunoprecipitation assays showed that N-Myc acted as a transrepressor, by recruiting the HDAC2 protein to an Sp1-binding site at the CCNG2 core promoter, in a manner distinct from its action as a transactivator. Moreover, HDAC2 was up-regulated, and CCNG2 down-regulated, in pre-cancerous and neuroblastoma tissues from MYCN (N-Myc) transgenic mice, and c-Myc over-expression correlated with up-regulation of HDAC2 and repression of CCNG2 in tumour tissues from pancreatic cancer patients. Taken together, our data indicate the critical roles of up-regulation of HDAC2 and suppression of CCNG2 in Myc-induced oncogenesis, and have significant implications for the application of HDAC inhibitors in the prevention and treatment of Myc-driven cancers.
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 4869.