bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3867: EGFR genotype impacts expression of chemotherapeutic target biomarkers in NSCLC
Authors: Liu H Eugene , Liu Jacqueline M. , Yu Ming-Chih , Bai Kuan-Jen , Lan Chieh 
Published: June 2012

Abstract
BACKGROUND: Non small cell lung cancer EGFR mutations are prevalent in the East Asian population, especially in female non-smokers, the L858R and del 747-753 in exons 18-21 of the EGFR tyrosine kinase domains are activating mutations with increased sensitivity to the EGFR tyrosine kinase inhibitors (TKIs) gefitinib and erlotinib. EGFR gene amplification also increases susceptibility to EGFR TKIs as has been reported in the IDEAL / INTACT non small cell lung cancer (NSCLC) trials. Our study evaluated chemotherapeutic target biomarkers in Chinese NSCLC patients with varying EGFR genotypes. METHODS: Seventy NSCLC patients with known EGFR genotype received chemotherapy and EGFR TKI therapy with known response and survival, their pathology specimen were retrospectively retrieved for evaluation. EGFR and KRAS were sequenced for mutations and deletions. Fluorescent in situ hybridization (FISH) was performed for EGFR genes. Immunohistochemical analyses were performed for topoisomerase 1, c-myc, RRM-1, class III beta tubulin, topoisomerase IIα, p53, thymidylate synthase, and ERCC-1. The percentage of nuclear-stained malignant cells were recorded for T IIα, T1, p53, ERCC-1, c-myc, whereas for TS, tau, RRM-1, class III beta tubulin were cytoplasmic stains, only positive or negative was reported, eventually only 63 patients had complete data for evaluation. RESULTS: Significant increase in overall survival was found in females (p=0.002), non-smokers (p=0.005), younger age (p=0.001), less advanced staging (p=0.048), EGFR mutation (p=0.038); but not with KRAS genotype, or expression of any chemotherapeutic markers. Patients in this study were consecutive patients, 60-70% received treatment. When EGFR mutant tumors were compared to EGFR wildtype tumors, the mutant tumors had lower KRAS mutation (4% vs 19%, p=0.1238), more were ERCC1- (76% vs 63%, p=0.2925), more topoisomerase 1 + (28% vs 17%, p=0.3719), less RRM1+ (24% vs 35%, p=0.4142), more TS- (93% vs 86%, p=0.4478), lower class III beta tubulin (45% vs 57%, p=0.4515). CONCLUSIONS: A difference in expression of chemotherapeutic target markers has been detected in differing EGFR genotypes, although its significance has been dampened by our small patient population, and larger patients groups will be needed to evaluate the impact of different chemotherapies on survival of the different EGFR genotype tumors.
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 3867. doi:10.1158/1538-7445.AM2011-3867
Abstract 387: Prostate cancer cell invasion is stimulated by cross communication with human monocyte-lineage cells
Authors: Lindholm Paul F. , Sivapurapu Neela , Jovanovic Borko , Crawford Susan E. 
Published: June 2012

Abstract
Tumor-associated macrophages (TAMs) produce factors that may stimulate tumor growth, angiogenesis and progression. In this study, co-cultures with monocyte-derived THP-1, U-937 cells or normal peripheral blood monocytes stimulated PC-3, DU145 and LNCaP prostate cancer cell basement membrane invasion. This study investigated the interactions between monocytes and prostate cancer cells leading to increased cancer cell invasion. The PC-3 prostate cancer cells expressed high levels of IL-6 and IL-8, at similar levels to co-cultures with human U-937 monocyte-derived cells. However, the co-culture supernatants showed increased MCP-1 levels, up to 5 ng/mL, compared with prostate cancer cells cultured alone with MCP-1 less than 10 pg/mL. During the co-cultures, MCP-1 was first detected at 8 hours and increased over 3 days. Co-culture of U-937 or THP-1 monocytes with either DU145 or LNCaP cells also increased MCP-1 expression significantly above cancer cell or monocyte cultures alone. When cultured separately, the monocyte-lineage cells produced more MCP-1 than the cancer cells; however, MCP-1 expression increased more than 10-fold in the co-cultured prostate cancer cells. Addition of purified MCP-1 and IL-8 stimulated prostate cancer cell invasion to levels similar to the co-cultures. Further, addition of anti-MCP-1 neutralizing antibodies inhibited prostate cancer cell invasion when compared with control antibodies. Co-culture with U-937 cells also stimulated NF-κB DNA binding activity in the prostate cancer cells. Transfection of the prostate cancer cells with dominant negative IκBα or treatment of the co-cultures with Bay11-7082 or Lacticystin inhibited NF-κB DNA binding and prostate cancer cell invasion. These experiments demonstrate that human monocyte-derived cells can cross-communicate with prostate cancer cells leading to increased cancer cell invasion. These studies have potential to identify treatments to target MCP-1 and NF-κB activity to inhibit monocyte-induced cancer cell invasion and progression. Support by Northwestern University Prostate S.P.O.R.E. P50CA90386 and CDMRP DAMD-17-02-1-0162
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 387. doi:10.1158/1538-7445.AM2011-387
Abstract 3872: Differentially expressed stem cell markers in breast cancer stem cells
Authors: Lobba Aline RM , Forni Maria Fernanda PAD , Perozzi Carolina , Carreira Ana Claúdia O. , Labriola Leticia , Sogayar Mari Cleide 
Published: June 2012

Abstract
The recently emerged concept of cancer stem cell (CSC) has led to a new hypothesis about tumor progression. Basically, the CSC theory hypothesizes the presence of a hierarchically organized, relatively rare population of cells, which is responsible for tumor initiation, self-renewal and maintenance, in addition to mutation accumulation and resistance to chemotherapy. CSCs have recently been described in breast cancer. Different markers have been used to isolate breast cancer stem cells; however, none of these proved to be very efficient. Furthermore, the lack of specific markers limits a precise characterization of these cells and their clinical application, especially in the development of therapeutic protocols. In the present work, we set out to search for enriched subpopulations of CSCs. To this end, we investigated the profile of different surface markers in normal and tumoral breast cancer cell lines. We analyzed the expression of cd44, cd31, cd90, cd200, cd14, cd34, cd31, cd105, c-kit, abcg2 and cd29 in MCF10-A, MCF-7, MDA-MB-231, MDA-MB-435 and Hs578-T cells lines using quantitative RT-PCR. As a result of this effort, we were able to identify two distinct markers presenting differential expression between normal and tumor cells. While one marker was increased in the malignant cells lines, the other one presented higher levels of expression in the normal cell line. Based on this study, we propose a new set of markers, which should allow both isolation and characterization of breast cancer stem cells. Upon informed consent, a number of normal and tumor human breast samples are currently being collected for the final proof of concept. These results contribute not only to a deeper understanding of the Biology of CSCs, but, also, to the development of optimized therapeutical approaches to breast 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 3872. doi:10.1158/1538-7445.AM2011-3872
Abstract 3874: An isogenic cell line approach to MMTV integration site analysis
Authors: Knepper Janice E. , Acosta Lauren , Saunders Justin , Tio Chong-Wai , Wang Tianjiao , Danielson Keith G. 
Published: June 2012

Abstract
Development of mammary tumors in mice carrying the retrovirus, mouse mammary tumor virus (MMTV), occurs by insertional mutagenesis in which viral transcriptional regulatory elements drive increased expression of adjacent genes. Several oncogenes have been identified due to their ability to cause loss of cell growth control in this system. However, most virus positive tumors feature multiple integration sites, and determination of which may be significant in tumor growth represents a challenge to validation of importance of integration site genes. We have developed a panel of more than 20 independent cell lines derived from MMTV-induced tumors of BALB/c mice. Analysis of common integration sites led to the identification of Tmem170, encoding a predicted transmembrane protein of 144 amino acids. Tmem170 RNA is highly expressed in several cell lines in the panel, but not in normal mouse mammary gland. Rabbit antiserum against a peptide in the predicted extracellular domain revealed a single band migrating at approximately 40 KDa in SDS gels. We developed a panel of vectors encoding silencing RNAs targeting Tmem170 and introduced these into cell lines expressing the Tmem170 RNA. Two independent cell lines exhibited decreased doubling times in culture when Tmem expression was silenced. The cells were introduced into the mammary fat pads of isogenic BALB/c mice and silenced lines exhibited dramatically decreased tumor growth. These studies support Tmem170's oncogenic role in tumor growth. In addition, the use of an easily manipulated cell line model for assessing the contribution of upregulated genes to tumorigenesis in immune competent animals allows for testing of other potential oncogenes.
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 3874. doi:10.1158/1538-7445.AM2011-3874
Abstract 3888: Ionizing radiation destabilizes inverted ALU repeats linked to LOH
Authors: Ho Bay , Singh Sheetal , Shih Shyh-Jen , Baker Pamela M. , Do To Uyen , Vaughan Andrew T.M 
Published: June 2012

Abstract
Ionizing radiation is a potent inducer of Loss of Heterozygosity (LOH), driven primarily by DNA double strand breaks. Such a process impacts both tumorigenesis through deletion of linked tumor suppressor genes and, similarly, the potential development of radiation resistant tumor clones during radiation therapy. The human mucoepidermoid cell line, H292, was exposed to either 4 or 8 Gy and surviving clones developed from two rounds of cloning analyzed for LOH using polymorphic microsatellite markers. A high level of LOH was observed within individual clones extending from 11q21 to 11q24 (6/49 after 4 Gy and 8/50 after 8Gy). More detailed analysis using a SNP screen on selected LOH positive clones indicated a sharp telomeric termination of LOH adjacent to a common SNP location. The telomeric extent of LOH observed co-mapped to a region of elevated recombination instability documented previously using linkage analysis. Further, SNP analysis showed a region of approximately 1 Mbp LOH that included the region of recombination instability identified through linkage analysis, in some clones isolated either with or without irradiation. The consistency of the telomeric boundary of LOH observed in the irradiated clones permitted a targeted analysis of DNA double strand breaks at this location, using LM-PCR, both before and after 4Gy irradiation of the same cell line. Using a six primer set screen covering a 9 kbp region at the telomeric extent of radiation-induced LOH, a single primer set showed an elevation in DNA breaks from 2-8h after irradiation. The timing and discrete distribution of such breaks indicated that these were not directly induced by the radiation itself. Cells that were unirradiated were not affected. Further inspection of the location demonstrating selective radiation-linked fragmentation showed the presence of an ALU inverted repeat, separated by approximately 1kbp, where the DNA breaks determined by LM-PCR were clustered within the 5’ ALU. Others have shown previously that inverted ALU repeats separated by &lt;20bp are recombinationally unstable and are underrepresented within the human genome. It is proposed that, within the H292 cell line, otherwise stable ALU inverted repeats are capable of forming a transient hairpin conformation, perhaps facilitated by their own transcription via RNA polymerase III, which is unstable within a genome undergoing DNA damage and repair. The combination of such inverted ALU repeats and genotoxic exposure, such as during radiation therapy, may therefore destabilize specific regions of the genome and contribute to the development of aberrant cell clones.
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 3888. doi:10.1158/1538-7445.AM2011-3888
Abstract 390: Increased orthotopic pancreatic tumor cell growth in obese mice
Authors: Gorden Lee , VanSaun Michael N. 
Published: June 2012

Abstract
Pancreatic cancer remains one of the eight deadliest cancers due to its late detection and high propensity to metastasize. Increased risk for the development of pancreatic cancer has been associated with obesity, type II diabetes and pancreatitis. The contribution of adipocytes and adipokines to pancreatic cancer progression remains largely unknown and requires further analysis. We hypothesize that increased pancreatic fat compromises the pancreatic microenvironment and increases primary tumor growth as well as metastasis. The condition of non-alcoholic fatty pancreatic disease has been characterized in humans as well as mice and lymph node positive patients were found to have increased pancreatic fat1,2. Adipose secreted cytokines, also known as adipokines, have both been implicated in various aspects of cancer cell survival, growth, and migration. To understand the influence that increased pancreatic fat has on the growth of tumors, both primary and metastatic, we have investigated a high fat diet induced murine model. Male mice fed a 42% fat diet for three months develop increased inter-pancreatic and intra-pancreatic fat as well as acute localized pancreatitis when compared to mice fed a 13% fat diet. To test the affect of pancreatic fat on tumor cells, we used an orthotopic tumor injection model to determine the rate of primary tumor growth and progression to metastasis. Further, we are implementing the use of Panc02-luciferase tagged cells to monitor and measure pancreatic tumor growth over time and to detect the presence of metastases in the liver and/or lungs. Preliminary evidence has confirmed that orthotopic tumors grown in obese mice led to an increased tumor size as well as massive expansion of tumor cells into the interpancreatic fat. In conclusion, increased pancreatic fat promotes the growth of orthotopically implanted murine tumor cells, yet the molecular mechanisms remain undetermined.
1. Mathur, A. et al. J Am Coll Surg. 2009 May;208(5):989-94.
2. Mathur, A. et al. HPB (Oxford). 2007;9(4):312-8.
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 390. doi:10.1158/1538-7445.AM2011-390
Abstract 4002: Epigenetic control of a checkpoint for miRNA tolerance
Authors: Li Qunfang , Tainsky Michael A. 
Published: June 2012

Abstract
The interferon (IFN) pathway controls the cellular response to viral infection and double-stranded RNA. We have found that this pathway provides a novel checkpoint for enhanced expression of miRNAs. The IFN pathway is abrogated in fibroblasts from Li-Fraumeni Syndrome (LFS) patients during spontaneous cellular immortalization, a necessary step in carcinogenesis. Interferon stimulated genes (ISGs) were down-regulated by epigenetic silencing during immortalization and some of these same ISGs were activated by replicative senescence. Bisulfite sequencing of the promoter regions of IFN-regulatory transcription factors (IRF5 and IRF7) revealed that IRF7 but not IRF5 was epigenetically silenced by methylation of CpG islands in immortal LFS cells. The re-activation of ISGs by those transcription factors is sufficient to inhibit cell proliferation and induce a senescence-related phenotype in immortal LFS cells. Similar epigenetic silencing of IRF7 also results in disruption of IFN pathway in ∼30% lung cancer cells and primary tissues. Examination of innate immunity status in normal bronchial epithelial cell line Beas2B, its ras transformed derivative BVK cells and tumor-generating clones reveals increasing loss of functional IFN pathway as cells become more cancerous. Furthermore, microarray profiling of differentially expressed microRNAs (miRNAs) in LFS cell lines revealed most miRNAs were up-regulated in IFN-pathway-defective MDAH087-10 fibroblasts compared to MDAH087-N cells with relatively normal IFN signaling. Overexpression of Dicer, a critical enzyme in miRNA biogenesis, promoted cell growth and colony formation in MDAH087-10 cells. However, double-stranded miRNA produced by Dicer enhanced the expression of ISGs in MDAH087-N cells resulting in significant cell death and reduced cell growth. In addition, manipulation of the IFN pathway in immortal LFS fibroblasts through transcription factor IRF7 reversed their response to Dicer overexpression due to altered activation of the IFN pathway. Dicer-overexpressing MDAH087-N cells contained lower levels of miRNA than vector control, and conversely much higher miRNA expression was detected in Dicer transfected MDAH087-10 cells. The higher miRNA tolerance in immortal LFS fibroblasts with a disrupted IFN pathway indicates for the first time that the IFN pathway as mediated through the transcription factor IRF7 must be disrupted to permit miRNA up-regulation to occur in early carcinogenesis. This IFN pathway appears to provide a checkpoint for miRNA level tolerance and its abrogation by epigenetic silencing leads to cellular immortalization and early events in tumorigenesis.
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 4002. doi:10.1158/1538-7445.AM2011-4002
Abstract 4004: Mislocalization of ATBF1 is associated with progression of head and neck squamous cell carcinoma
Authors: Sun Xiaodong , Li Jie , Sica Gabriel , Fan Song-Qing , Wang Yuxiang , Chen Zhengjia , Muller Susan , Chen Zhuo G. , Shin Dong M. , Dong Jin-Tang 
Published: June 2012

Abstract
Purpose: In prostate, breast and gastric cancers, the nuclear protein AT-motif Binding Factor 1 (ATBF1) undergoes frequent reduced mRNA expression and genomic alterations. However, the protein level and subcellular localization of ATBF1 have not been well studied in human cancers. In the present study, we examined ATBF1 expression, localization and function in head and neck squamous cell carcinomas (HNSCCs).
Experimental Design: ATBF1 expression and localization were examined by immunohistochemistry in a series of 197 surgically dissected HNSCC specimens and correlated with clinical outcomes. In addition, ATBF1 expression was characterized in five HNSCC cell lines. We then mutated the nuclear localization signal (NLS) of ATBF1 and studied the effects of cytoplasmic versus nuclear ATBF1 on the growth kinetics of the 212LN cell line.
Results: ATBF1 had a predominantly nuclear localization in hyperplastic squamous epithelium, and nuclear ATBF1 dramatically decreased in invasive tumors. Conversely, cytoplasmic ATBF1 levels progressively increased from dysplasia to invasive tumors. Cytoplasmic ATBF1 levels were significantly inversely correlated with overall survival and disease free survival. Similar expression patterns and subcellular localization of ATBF1 were observed in HNSCC cell lines. In order to better define the role of subcellular localization of ATBF1, we identified and mutated its nuclear localization signal (NLS). Mutation of the NLS converted the inhibitory effect of ATBF1 on cell growth to growth-promoting.
Conclusions: Aberrant cytoplasmic localization of ATBF1 is significantly associated progression of HNSCC, and cytoplasmic ATBF1 may be a potential biomarker for its early detection. Our results suggest that nuclear ATBF1 functions as a tumor suppressor in head and neck squamous epithelial cells and that this tumor suppressor effect is sequestered by cytoplasmic localization during HNSCC 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 4004. doi:10.1158/1538-7445.AM2011-4004
Abstract 4239: Pterostilbene, a natural polyphenol, elicits full protection against ultraviolet B radiation-induced skin carcinogenesis: Preclinical studies
Authors: Feddi Fatima , Mena Salvador , Ortega Angel , Asensi Miguel , Estrela Jose M. 
Published: June 2012

Abstract
Solar radiation exposure is the chief cause of nonmelanoma (i e, basal cell and squamous cell) skin cancer, and it is also a prime factor in the etiology of cutaneous melanoma The cancer-causing effects of ultraviolet (UV) radiation on the skin are mainly produced by UV-B radiation in the 290- to 320-nm range, the same range that produces burning in human skin (erythema) UV-B exposure can damage DNA and be immunosuppressive Thus, and considering the alarming numbers of skin cancers being diagnosed around the world, it is increasingly evident the need of effective protection from UV radiation
Resveratrol (trans-3,5,4′-trihydroxystilbene; RES) is a phytoalexin present in a wide variety of plant species, where its synthesis is induced by stress conditions The cancer chemopreventive activity of RES was first reported by Jang et al [Science 275, 218 – 220 (1997)] in a model of skin carcinogenesis where topic administration of this polyphenol inhibited multistage mouse skin carcinogenesis Equally promising action is exerted by resveratrol analogues, mainly pterostilbene (3,5-dimethoxy-4′-hydroxy-trans-stilbene: PTER), which shows a higher half-life in vivo and more potent anticancer effects in vivo than RES Our aim was to compare the anticancer effects of RES and PTER in UVB-induced mouse skin carcinogenesis In our experiments, Female SKH-1 hairless mice were irradiated with UVB (180 mJ/cm2; 3 doses/week; for a total of 30 weeks) 20 min after or before the topical administration of liposomes containing a total of 10 μmol of RES or PTER/mice (aprox 2 5 μmol/cm2 of skin) This long-term UVB administration reproduces, in an animal model, which are the consequences in humans of receiving chronic UVB radiations We observed that pretreatment of the skin with PTER resulted in a dramatic reduction in UVB-induced skin tumorigenesis (90 % of tumor free-mice at the end of treatment, n=20; P&lt;0 01), whereas all RES-treated mice showed carcinomas (0 % of tumor free-mice on the 30th week, n=20) Molecular mechanisms involved in this strong anticancer effect elicited by Pter (as compared with RES) suggest differences in prevention of DNA mutagenesis, and protein and lipid oxidation Our results indicate that PTER can be used efficiently in the prevention of skin carcinogenesis induced by solar radiation.
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 4239. doi:10.1158/1538-7445.AM2011-4239