bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 462: Targeting hepatocellular carcinoma by suppressing HIF-1 alpha alone and in combination with therapeutic drugs
Authors: Xie Zhi , Wu Xin , Wang Kai , Pocalyko David , Yeom Young-II , Yoo Hyang-Sook 
Published: February 2011

Abstract
Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide and the third most common cause of cancer related death. HIF-1 alpha (HIF1α) is overexpressed in many human cancers as a result of intratumoral hypoxia as well as genetic alterations, such as gain-of-function mutations in oncogenes and loss-of-function mutations in tumour-suppressor genes. It has many important functions including angiogenesis, survival, chemo-resistance metastasis, and glucose metabolism. The overexpression of HIF1α is associated with poor prognosis in many types of cancer. To understand the role of HIF1α in HCC, we analyzed the HIF1α gene expression in the clinical tumor tissues and found that HIF1α mRNA was upregulated compared with the non-tumor adjacent tissue. This upregulation was positively correlated with the poor overall survival and disease free survival of the HCC patients. In addition, we knocked down the HIF1α expression by siRNA and examined its impact on the growth of a panel of HCC cell lines under both hypoxia and normaxia conditions. HIF1α siRNA suppressed 90% of HIF1α mRNA and 50% of its protein expression without affecting the expression of HIF1β and HIF2α. Hep1 and Snu182 cell lines were sensitive to HIF1α suppression (&gt;70%) while Huh 7.5 and SNU398 showed little response. The effect of HIF1α on cell growth inhibition is similar under both hypoxia and normoxia conditions. PDGFR and mTOR were reported to regulate HIF1α synthesis. We examined the efficacy of rapamycin and PDGFR inhibitors in combination with HIF1α siRNA. We found differential response in different HCC cell lines. Rapamycin had limited suppression on both Hep1 and SNU182 cell growth. When combined with HIF1α siRNA, we observed significantly enhanced suppression. PDGFR inhibitor suppressed Hep1 and SNU182 in a dose-dependant manner and the efficacy was further enhanced when combined with HIF1α. To understand the molecular mechanism of HIF1α function, we carried out the gene expression analysis on these “sensitive” and “resistant” cell lines under different treatment conditions. The differential expression signature will provide important insight to the function of HIF1α and the other targeted therapeutic drugs in these HCC cell lines. It will also provide understanding of possible resistance mechanisms and combinational drug strategy to overcome these resistances.
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 462.
Abstract 4625: A biotin-label-based antibody array for high-content profiling of protein expression
Authors: Huang Ruochun , Jiang Weidong , Yang Jean , Mao Ying Qing , Zhang Ying , Yang Weiming , Yang Dongzi , Burkholder Brett , Huang Rani Yan , Huang Ruo-Pan 
Published: February 2011

Abstract
Abstract:
Profiling protein expression on a global scale will have significant impact on biomedical research, particularly in the discovery and development of drugs and biomarkers. Through the years, several antibody array systems have been invented and developed for multiple protein detection. However, a reliable and high-content system for protein profiling from many biological samples has yet developed. To address this problem, we have developed a high density antibody array and used this technology to uncover the potential biomarkers of ovarian cancer. In this approach, biological samples are conjugated with biotin. Antibody arrays are then used to capture the biotinylated proteins. The presence of proteins captured by the antibody chip is detected using streptavidin-conjugated fluorescent dye (Cy3 equivalent) as a reporter. The signals, which are visualized by laser scanning, are normalized using positive, negative, and internal controls. Using this biotin-label-based antibody array technology, the expression levels of 507 human, 308 mouse, 90 rat target proteins can be simultaneously detected, including cytokines, chemokines, adipokines, growth factors, angiogenic factors, proteases, soluble receptors, soluble adhesion molecules, and other proteins in a variety of samples. Most proteins can be detected at pg/ml and ng/ml levels with a CV of less than 20%. Using human biotin-based antibody arrays, we screened the serum expression profiles of 507 proteins in 47 ovarian cancer patients and 39 normal subjects. A panel of protein expression showed significant difference between normal and cancer (P&lt;0.05). By Classification Analysis and Split-Point Score Analysis of these two groups, a small group of proteins can be used to distinguish ovarian cancer patients from normal subjects and between ovarian cancer patients and normal subjects. Our results suggest the biotin label-based antibody arrays that we have developed have great potential in applications for biomarker discovery.
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 4625.
Abstract 4629: Expression of cancer-associated proliferating cell nuclear antigen (caPCNA) in various stages and types of neoplasia (breast, cervix, colon, gastric, lung, ovary, thyroid, and uterus)
Authors: Sandusky George E. , John Karla , Gulley Patty , Carr Katie , Cheng Liang , Malkas Linda H. , Hickey Robert 
Published: February 2011

Abstract
Novel immunohistochemistry biomarkers that target specific cellular proteins that are either uniquely or primarily expressed by cancer cells are being developed. One of these biomarkers, caPCNA, [the cancer associated isoform of PCNA] may be useful as an aide for distinguishing early stage neoplasia from hyperplasia in clinical cases that are often difficult to interpret. The caPCNA isoform appears to be expressed almost exclusively in a large variety of cancer cells and at all Stages [1 to 4] of the disease. It is not consistently observed in most normal adjacent tissues. This study analyzed the expression of caPCNA, by immunohistochemistry (IHC) using an automated Ventana immunostaining platform. In the present study, IHC was performed on neutral buffered formalin fixed paraffin embedded tissues obtained from various pathology labs. Evaluation of carcinomas (120 cases) from various organs and clinical stages as well as normal adjacent tissue was performed. Immunostaining was localized in tumor cells only to the cell nucleus. CaPCNA expression was seen in 10 of 10 cervical Ca, 20 of 20 colon Ca, 10 of 10 thyroid Ca, 10 of 10 gastric Ca, 10 of 10 ovarian Ca, 25 of 25 breast Ca, 10 of 10 lung Ca, 11 of 12 uterine Ca, and 15 of 15 DCIS Ca. On a normal tissue panel, caPCNA immunostaining was seen in macrophages, syncytial trophoblasts in the placenta, GI tract crypt epithelial cells, and scattered staining in the basilar layer of the skin. Immunostaining of normal macrophages and most of the other reactive cell types was abolished by removal of the heavy chain of the primary antibody during creation of an Fab2' fragment of the anti-caPCNA antibody. In summary, the present results illustrate the localization of caPCNA at all stages, in many different types of neoplasms. CaPCNA may therefore be a useful biomarker for early stage cancer diagnosis and potentially maybe a predictor of patient outcome.
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 4629.
Abstract 463: Hypoxia leads to impaired differentiation and sustained global histone acetylation in immortalized mammary epithelial cells cultured as acini
Authors: Vaapil Marica , Helczynska Karolina , Beckman Siv , Påhlman Sven , Jögi Annika 
Published: February 2011

Abstract
We study the effect of hypoxia on mammary epithelial cell differentiation at a non-malignant stage as a putative step in early malignant progression. Due to inadequate vasculature solid tumors often contain regions with low oxygen levels (hypoxia). Hypoxia is associated with increased metastatic potential and worse patient outcome. The hypoxic response is in large driven by the two transcription factors hypoxia inducible factor (HIF) 1 and HIF 2.
We have reported that hypoxia leads to a less differentiated phenotype in breast cancer and in neuroblastoma, and in the clinic low tumor cell differentiation is related to poor prognosis in these diseases. To investigate the effect of hypoxia on mammary epithelial cell differentiation we employed the model of acinar morphogenesis. In this model immortalized mammary epithelial cells in three-dimensional (3D) culture on a laminin-rich matrix differentiate and form acini-like structures with evacuated lumen surrounded by polarized cells. We have previously seen that hypoxia (1% oxygen) impairs the process of acinar morphogenesis. The hypoxic cells failed to obtain polarity and markers of differentiation were affected at expression level as well as cellular localization. Addressing the mechanism behind the hypoxia-impaired differentiation, we find that hypoxia impairs the global histone deacetylation that is associated with changes in cell morphology and differentiation of the mammary epithelial cells. Three days post-seeding, during the proliferation stage, both normoxic and hypoxic cells stained positive for acetylated histone 4 (AcH4). When the normoxic cells go through morphological changes and acinar formation the acetylation of histone 4 is reduced whereas it is maintained in the hypoxic cell-clusters 10 days after seeding. Transfer of acini from normoxia to hypoxia at this time-point leads to an increase in AcH4. Thus, the hypoxic condition prevents global deacetylation, which is generally associated with high level of transcription and an undifferentiated proliferative cell state, rendering the cells an open chromatin state and hindering acinar formation. These data indicate that hypoxia promotes loss of differentiation also at a non-malignant stage.
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 463.
Abstract 4634: Decreased infiltration of macrophage scavenger receptor in non-malignant biopsy specimens is associated with detection of prostate cancer
Authors: Takayama Hitoshi , Hatano Koji , Kawashima Atsunari , Mukai Masatoshi , Nagahara Akira , Nakai Yasutomo , Nakayama Masashi , Nishimura Kazuo , Okuyama Akihiko , Nonomura Norio 
Published: February 2011

Abstract
INTRODUCTION AND OBJECTIVE: Screening for prostate cancer (PCA) has become widespread practice. Many men with negative biopsy findings undergo repeat biopsies to rule out PCA. It should be long enough to avoid unnecessary biopsies and costs. The discovery of new predictors is essential to establish appropriate repeat biopsies. Several predictors of subsequent PCA detection have been described. Especially, chronic inflammation is considered to be a risk factor for PCA. The macrophage scavenger receptor (MSR) has been reported to play a role in recognizing foreign pathogenic substances. MSR-positive inflammatory cells are often seen in solid tumors. Tumor-associated macrophages (TAM) have been shown to positively or negatively regulate the growth of various malignant cells. However, the role of MSR and TAM in PCA carcinogenesis is unclear. In the present study, infiltration of MSR and TAM in non-malignant biopsy specimens was evaluated as a possible predictive value for PCA.
METHODS: These reviews were evaluated for 92 patients ranging from 51 to 82 years (median, 69 years), who received repeat needle biopsies of the prostate and were diagnosed as non-malignant during first biopsy. Of these, 30 (32.6%) were positive for cancer during second or third biopsy. TAM and MSR were immunohistochemically labeled using a monoclonal (CD68 and CD204) antibody. For systematic counting, 6 ocular measuring fields were randomly chosen under a microscope at a power of × 400 within first negative biopsy specimens.
RESULTS: There were no significant differences in PSA, Age and Interval of previous and subsequent biopsies, between negative and positive cases for cancer. Median count of MSR and TAM in each case was 32 and 16. MSR count in patients with cancer was lower than in patients without cancer (P &lt; 0.001). However, in TAM count there were no significant differences between patients with or without cancer. CONCLUSION: Decreased infiltration of MSR in non-malignant biopsy is associated with detection of PCA. MSR is predictor for appropriate repeat biopsies.
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 4634.
Abstract 4637: Mini-chromosome maintenance protein 7 as a potential theranostic biomarker in epithelial ovarian cancer
Authors: Ota Takayo , Clayton Amy C. , Minot Douglas M. , Hartmann Lynn C. , Shridhar Viji , Gilks Blake , Chien Jeremy R. 
Published: February 2011

Abstract
Mini-Chromosome Maintenance protein 7 (MCM7) is involved in replicative licensing and synthesis of DNA. It is previously identified as over-expressed gene in high-grade serous carcinomas compared to serous borderline tumors of the ovary in cDNA microarray studies. In this study, we sought to validate MCM7 expression in ovarian tumors by applying immunohistochemical analysis on tissue microarrays consisting of 445 ovarian tumors. MCM7 expression was quantified as MCM7 labeling index by determining the tumor nuclei positive for MCM7 staining as a percentage of total tumor nuclei. The labeling index scores were independently generated by two methods: PATH score provided by a manual review of each samples by a pathologist and ACIS score provided by Automated Cell Imaging System. Analyses of both scores indicated high degree of concordance in score distribution between PATH and ACIS. MCM7 expression is significantly higher in high-grade serous carcinomas compared to serous borderline tumors, confirming our previous cDNA microarray studies. In both PATH and ACIS analysis, MCM7 expression is also significantly higher in high-grade serous carcinomas compared to other histology subtypes of ovarian cancer. Finally, to identify the clinical significance of MCM7 expression, we determined the association between MCM7 expression and disease-free survival. MCM7 labeling index was dichotomized into two groups (high and low) using median labeling index as cut-off. For both PATH or ACIS-derived scores, univariate analyses indicate significant association of high MCM7 labeling index with better disease-free survival in high-grade serous carcinomas. These results suggest the clinical significance of MCM7 expression in high-grade serous carcinomas of the ovary and the need for further evaluation of MCM7 as a potential theranostic biomarker.
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 4637.
Abstract 4640: High expression of the stem cell marker LGR5 is associated with a poor clinical outcome in patients with Ewing's sarcoma
Authors: Scannell Christopher A. , Abdueva Diana , Ji Lingyun , von Levetzow Cornelia , Sposto Richard , Triche Timothy J. , Lawlor Elizabeth R. 
Published: February 2011

Abstract
Ewing's sarcoma family tumors (ESFT) are aggressive bone and soft tissue tumors that are most commonly diagnosed in childhood and adolescence. Unfortunately, drug-resistant relapse is not uncommon and is associated with very poor outcomes. No clinical or pathologic features currently exist that reliably predict chemosensitivity or relapse in newly diagnosed patients.
In this study we used whole genome expression microarray profiling to identify potential markers of drug resistance and relapse in ESFT.
Affymetrix human exon (HuEx) arrays were used to profile a highly drug resistant case of primary, localized ESFT before and after induction therapy. Comparison of gene summarized data from pre- and post-therapy samples with 10 chemosensitive tumors identified 309 genes to be differentially expressed in the resistant case at diagnosis (fold change&gt;2). Of the 309 differentially expressed genes at diagnosis, 130 demonstrated an even greater change in expression post-induction therapy suggesting that these genes might be markers of the most highly drug-resistant cells. Intriguingly, two stem cell associated genes, PROM1 (prominin 1) and LGR5 (leucine-rich-repeat containing G-protein-coupled receptor 5), were included in the list of putative chemoresistance markers. Expression of PROM1 and LGR5 were 18-fold and 17-fold higher, respectively, at diagnosis and 31-fold and 21-fold higher post-induction therapy in the drug resistant case. To determine if either gene is associated with chemoresistant disease or relapse in ESFT we next evaluated whether their expression correlated with outcome in a large cohort of institutional and Children's Oncology Group patients. Clinical correlates analysis of HuEx gene expression data obtained from 53 tumors revealed no correlation between PROM1 expression and outcome. In contrast, increased expression of LGR5 was associated with worse event-free (p=0.008) and overall survival (p=0.046). Variable but detectable expression of LGR5 in ESFT tumors and cell lines was validated using quantitative RT-PCR. Finally, LGR5 expression in ESFT cells was compared to human embryonic and somatic stem cells and fibroblasts. Significantly, LGR5 was found to be highly expressed by neural crest stem cells but not by bone-marrow derived mesenchymal stem cells, differentiated neural crest cells, or embryonic fibroblasts. These data suggest that LGR5 might be useful as a predictor of outcome in ESFT and implicate a primitive neural crest stem cell phenotype in the developmental origins of drug-resistant and relapsed disease.
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 4640.
Abstract 4641: Distinctive expression of polycomb group proteins Bmi1 and EZH2 in non-small cell lung cancers and their clinical and clinicopathological significance
Authors: Kikuchi Junko , Kinoshita Ichiro , Kikuchi Eiki , Konishi Jun , Shimizu Yasushi , Oizumi Satoshi , Nishimura Masaharu , Dosaka-Akita Hirotoshi 
Published: February 2011

Abstract
Background: The polycomb group genes, Bmi1 and EZH2, function as transcriptional repressors involved in gene silencing. They are involved in the malignant transformation and biological aggressiveness of several human carcinomas. In the present study, we evaluated Bmi1 and EZH2 protein expression in specimens of human non-small cell lung cancers (NSCLCs).
Methods: We conducted an immunohistochemical assessment of 157 surgically resected NSCLCs to evaluate the correlation between Bmi1 and EZH2 expression and various features, including clinical, clinicopathological and biological characteristics.
Results: Normal bronchial epithelia showed abundant expression of Bmi1 and sporadic expression of EZH2. NSCLC patients with high EZH2 expression in tumor cells showed poorer prognosis than those with low EZH2 expression in all pStages (p = 0.001) and in pStage I (p = 0.006). Multivariate analysis showed that high EZH2 expression was a independent unfavorable prognostic factor in pStage I patients (p = 0.048). High EZH2 expression was significantly correlated with non-adenocarcinoma histology (p = 0.001), moderate and poor differentiation (p = 0.001), advanced pT stage (p = 0.02), and high Ki-67 and cyclin E labeling index (p &lt; 0.001). Bmi1 expression, in contrast, was not a significant prognostic factor, and was not correlated with any clinicopathological factors other than early pT stage.
Conclusion: Bmi1 and EZH2 show characteristic and distinctive expression in NSCLCs. High EZH2 expression is correlated with tumor aggressiveness, and may provide a novel prognostic marker for NSCLCs.
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 4641.
Abstract 4651: Elevated serum tissue inhibitor of metalloproteinases-1 (TIMP-1) level predicts shorter survival in ovarian cancer
Authors: Jamshidi Navid , Shrivastava Vikas , Leitzel Kim , Ali Suhail , Podczask Edward , Macneill Colin , Deimling Timothy , Brown-Shimer Sheryl , Pierce Karen , Carney Walter , Rizvi Syed , Abbi Kamal , Lipton Allan 
Published: February 2011

Abstract
Body: Background: Matrix metalloproteinases (MMPs) play a key role in invasion and metastasis of cancer cells. MMPs are able to degrade extracellular matrix and aid formation of new blood vessels, thus supporting metastatic tumor growth and angiogenesis. The MMP family can be regulated by their inhibitors, the tissue inhibitor of metalloproteinases (TIMPs), which bind MMPs noncovalently. TIMP-1 has paradoxical multifunctional roles in tumorigenesis, independent of its original MMP-inhibitory role: growth promotion, inhibition of apoptosis, and regulation of angiogenesis. Overexpression of TIMP-1 confers resistance to chemotherapy in cell culture, and increased TIMP-1 has been associated with an unfavorable prognosis in multiple cancer types. TIMP-1 has recently been reported to be a predictive biomarker in large human breast cancer trials. The purpose of this study was to determine the correlation between serum TIMP-1 levels at the time of diagnosis in patients with ovarian cancer and correlate this biomarker with overall survival.
Methods: Serum TIMP-1 was assayed from 36 patients diagnosed with ovarian cancer between 1982 and 1987. Blood was collected at the time of diagnosis and serum frozen. Serum TIMP-1 levels were measured using a TIMP-1 ELISA from Oncogene Science / Siemens Healthcare Diagnostics (Cambridge, MA). Clinical outcome data were correlated with serum TIMP1 levels.
Results: TIMP-1 levels from 36 patients had a mean of 559 ng/ml with SD of + 296 (range 145 to 1460 ng/ml). 35 of 36 patients had clinical follow up data available. 82.14% of patients had distant metastasis, 7.14 % had localized tumor, and 10.71 % had regional involvement. Elevated serum TIMP-1 level predicted shorter survival in ovarian cancer by quartile analysis (p=0.022). Median survival was 4079 days for patients with the lowest serum TIMP-1 quartile, and 106 days for those with the highest serum TIMP-1 quartile. On a continuous basis, higher serum TIMP-1 trended to predict significant shorter survival (p=0.063).
Conclusions: Elevated serum TIMP-1 levels at the time of diagnosis predicted shorter survival in ovarian cancer. Circulating TIMP-1 deserves further study as a predictive and prognostic factor in ovarian 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 4651.