bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3095: The molecular, cellular, and physiological consequences of disrupting the HIF-1α interaction
Authors: Reece Kelie M. , Pisle Stephen T. , Richardson Emily D. , Cook Kristina M. , Price Douglas K. , Figg William D. 
Published: June 2012

Abstract
Many cancers contain regions of hypoxia due to rapid cell proliferation and the presence of blood vessels within the tumor that are structurally and functionally abnormal, resulting in the heterogeneity of blood flow. This state of hypoxia is associated with increased risk of treatment failure, metastasis and patient mortality. A principal mechanism by which cancer cells adapt to the hypoxic microenvironment is through the activity of hypoxia-inducible factor 1 (HIF-1), a heterodimeric transcription factor composed of an O2-regulated HIF-1α subunit that dimerizes with a constitutively expressed HIF-1β subunit. HIF-1α expression under hypoxic conditions regulates hundreds of genes including those that play key roles in invasion/metastasis, angiogenesis, tumor cell immortalization, and resistance to chemotherapy and radiation. Therefore, the inhibition of transcription driven by HIF has the potential for cancer treatment. One way to reduce the activity of this protein is by disrupting the complex that HIF forms with p300, an essential transcriptional coactivator. Previous data from our laboratory showed that several members of the epidithiodiketopiperazine (ETP) family of natural products are able to block the interaction between HIF-1α and p300. Here, we extend these studies by examining the comprehensive effect that select ETPs have on the disruption of the HIF/p300 complex at the molecular, cellular, and physiological levels. We began our studies by performing a series of rat aortic ring assays to determine the antiangiogenic effect of selected ETPs, namely chetomin, chaetocin, and gliotoxin. Chetomin and chaetocin concentrations of 50 nM inhibited approximately 90% of outgrowth, while 500 nM of gliotoxin was needed to achieve a similar effect; these compounds had GI50 of 22, 11, and 175 nM, respectively. In ongoing work, we hope to determine if the antiangiogenic effects that were observed in our rat aortic ring assays, are due to disruption of the HIF/p300 complex. To this end we are immunoprecipitating the complex from cells in the absence or presence of the aforementioned ETPs. The molecular consequences of blocking the HIF/p300 interaction will be assayed by qRT-PCR for hypoxia-regulated genes such as VEGF and GLUT1; cell proliferation and migration assays will also be performed to monitor cellular effects. Together, these results will be key in determining the feasibility of targeting this interaction for cancer therapeutics.
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 3095. doi:10.1158/1538-7445.AM2011-3095
Abstract 314: Distinctive genomic signature patterns of common Hematological malignancies uncovered by chromosomal microarray analysis (CMA) using a cancer-specific microarray
Authors: Li Marilyn M. , Hu Xiaofeng , Freeman Christopher E. , Carmack Condie E. , Iqbal Anwar 
Published: June 2012

Abstract
The application of chromosomal microarray analysis (CMA) in cancer research has produced a wealth of useful information about copy number alterations (CNAs) and their implications in cancer classification, disease progression, therapy response, and patient outcome. However, only a handful of clinical laboratories are offering CMA for cancer diagnosis. This is largely due to the lack of effective diagnostic standards and guidelines for cancer applications, and the absence of a cancer microarray database to aid in post-analytic interpretation. We have designed a combined targeted-/whole-genome array specific for cancer using the microarray CGH format. Approximately 20,000 high quality oligonucleotide probes were selected from the Agilent Tech. (Santa Clara, CA) eArray system to target all exons and exon/intron boundaries of more than 500 cancer genes, over 100 known cancer-associated genomic regions and all subtelomeric chromosome regions. Intervals between aforementioned genes or regions were filled relatively evenly with oligonucleotide probes to cover the whole genome. Using this custom designed array, we studied 250 cases of hematological malignancies and 30 normal bone marrow or blood controls. In addition to confirming and clarifying cytogenetic and FISH results, the array revealed many previously unknown CNAs, including intra-gene deletions and duplications in patients with normal or abnormal karyotype. Many apparently balanced translocations were found to harbor cryptic CNAs at or near the breakpoints. Many CNAs displayed strong association with specific category of malignancies. GeneSpring Hierarchical Clustering analysis showed distinctive genomic signature patterns for different types or sub-types of haematological cancers. Using BlueFuse Multi software, we were able to create a few disease classification/decision tracks, which are of great clinical significance in post-analytic interpretation and genotype-phenotype correlation for 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 314. doi:10.1158/1538-7445.AM2011-314
Abstract 3145: Comparing the reproducibility and prognostic value of proliferation markers Ki67, MAI, PPH3 in node negative breast cancer
Authors: Baak Jan P. , Gudlaugsson Einar , Skaland Ivar , Malpica Anais , Zhimin Shao , Janssen Emilius 
Published: June 2012

Abstract
Background. The proliferation factor Ki67 is prognostic but determination methods differ. Their reproducibility and independent prognostic value is largely unknown.
Aim. To evaluate the reproducibility of different Ki67 assessment methods and compare their prognostic value with Mitotic Activity Index (MAI), Phosphohistone-3 (PPH3) and other prognosticators.
Methods. In 240 T1,2N0M0 breast cancers without systemic adjuvant treatment, standardized automated quantitative immunohistochemistry was used for Ki7 and PPH3 and a strictly formalized protocol for MAI assessment. The percentages of Ki67 positive nuclei were assessed by two pathologists, computerized interactive morphometry (CIM) and fully automated digital image analysis (DIA). Reproducibility was studied by duplicate blind assessments. Continuous variables were discretized. We analyzed the prognostic value of widely used Ki67 thresholds (15%, 20%), others). We also tested at which places within the tumour (periphery, center), Ki67 was prognostically strongest. Univariate and multivariate survival analyses were performed.
Results. The Ki67 results of the two pathologists differed and their optimal prognostic thresholds greatly varied (4% and 14%). Moreover, Ki67% by one pathologist was well reproducible but not strongly prognostic, the other was strongly prognostic but not well reproducible. On the other hand, subjective Ki67% assessments were strongly prognostic (&lt;0.0001) over a wide range of Ki67% thresholds (between 5% and 20%) (with an optimum Hazard Ratio for thresholds between 10%-14%). DIA-Ki67 and CIM-Ki67 were very well reproducible (r&gt;0.99 and 0.94) and also strongly prognostic (P&lt;0.0001 for both methods). Ki67 determinations are prognostically strongest in the periphery of the tumor. DIA-Ki67-6.5 is the strongest prognosticator, overshadowing subjective Ki67 assessments, Ki67-15% and 20% thresholds, tumor diameter, grade, ER, PR, Her2, CK5-6. CIM-Ki67 is a cheap well reproducible strongly prognostic alternative. MAI (&lt;3 versus ≥3) or PPH3 (&lt;13 versus ≥13) were slightly prognostically stronger than Ki67-DIA and considerably stronger than Ki-67-CIM.
Conclusions. In node negative breast cancer without adjuvant systemic treatment, Ki67 by digital image analysis or computerized morphometry but not by subjective counts is well reproducible and prognostically strong. MAI or PPH3 were prognostically slightly stronger.
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 3145. doi:10.1158/1538-7445.AM2011-3145
Abstract 3153: Detecting PTEN deletions in prostate cancer using circulating tumor cells
Authors: Atwal Siminder Kaur , Savage Heidi , Mohan Sankar , Pandita Ajay , Hampton Garrett , Amler Lukas , Lackner Mark , Punnoose Elizabeth 
Published: June 2012

Abstract
The PI3K/Akt pathway is frequently activated in human cancers. A number of the components of this pathway are activated, mutated, amplified and deleted in a wide variety of human cancers highlighting the key role of this pathway. PTEN is a negative regulator of this pathway that is frequently inactivated in a variety of tumors. PTEN loss could be useful as a predictive biomarker to identify the tumors that are dependent on the PI3K/Akt pathway and therefore likely to respond to PI3K/Akt targeted agents.
PTEN is frequently deleted in prostate cancer with incidence as high as 75% reported in advanced disease. Both genetic models of PTEN loss in prostate cancer as well as associations of PTEN deletions with poor clinical outcome support a role for PTEN in prostate cancer progression. Determining PTEN status is challenging in metastatic prostate cancer since biopsies are infrequently performed in this setting. Circulating tumor cells (CTCs) could provide an alternate non-invasive source of tumor cells and relatively higher counts of CTCs have been reported in prostate cancer compared to other indications. Here we evaluate the utility of CTCs in determining PTEN status of patients with castration resistant prostate cancer (CRPC).
We evaluate whether we can detect PTEN loss in CRPC patient CTCs and in their respective tissue. We developed a PTEN FISH assay to score PTEN in spiked CTCs in blood and compared PTEN loss in CTCs (captured on the Cellsearch platform) with archival tissue available from CRPC patients. Our data suggests that predictive biomarker analysis in CTCs is possible and CTCs could be potentially used to predict PTEN loss.
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 3153. doi:10.1158/1538-7445.AM2011-3153
Abstract 3155: Identification of biomarkers of chemoresistance in serous epithelial ovarian cancer by integrative molecular profiling
Authors: Koti Madhuri , Vidal Ricardo , Haslehurst Alexandria , Nuin Paulo , Weberpals Johanne , Childs Timothy , Bryson Peter , Feilotter Harriet , Squire Jeremy , Park Paul C. 
Published: June 2012

Abstract
Development of primary resistance to carboplatin and paclitaxel pose a major challenge in the management of ovarian cancer. To identify the molecular mechanisms underlying this process, we used microarrays to profile the 1) copy number alteration and SNP, 2) mRNA, 3) miRNA and 4) methylation signatures in 11 chemoresistant and 13 sensitive tumour samples, as defined by the RECIST criteria. The profiles are analyzed by Bayes statistics, based on R/Bioconductor packages, and the relevant pathways determined using the Ingenuity Pathway Analysis. The data from each array platforms are integrated using bioinformatic analytical and visual tools developed in house to not only decipher the most critical biological pathways, but also to identify the molecular mechanisms driving the pathways. Analysis to date identified the metabolic network involving HNRNPC, JAK1, Erbb2, ARF1, among others, which converge to deregulate the PI3K pathway. Interestingly, this is consistent with PTEN loss which is frequently observed in serous low grade tumours. The complexity of this pathway is reflected by its implication in multiple biological functions including growth promoting pathways, proliferation, differentiation, anti-apoptosis, tumorigenesis and angiogenesis. The integrated analysis will dissect and elucidate the roles that the CNA, SNP, methylation and miRNA play in the deregulation of this and other pathways involved in primary chemoresistance. Our research findings will yield diagnostic and prognostic biomarkers that will lead to development of specific treatment regimens for the improved control of serous epithelial ovarian 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 3155. doi:10.1158/1538-7445.AM2011-3155
Abstract 3160: Clinical utility of circulating tumor cell monitoring for therapeutic response in gastric cancer patients
Authors: Hashimoto Yuuri , Uno Futoshi , Tsujino Yukio , Urata Yasuo , Kagawa Shunsuke , Fujiwara Toshiyoshi 
Published: June 2012

Abstract
Background: Circulating tumor cells (CTCs) in the peripheral blood are considered as a useful biomarker for disease outcome and treatment response because the presence of CTCs is associated with short survival. We previously established the biological imaging system to detect viable CTCs among millions of peripheral blood leukocytes using telomerase-specific replication-selective adenovirus expressing green fluorescent protein (GFP) (Kojima et al, J Clin Invest, 2010). In present study, we demonstrate the clinical potential of our method for monitoring the efficacy of treatment in patients with gastric cancer.
Methods: We used a GFP-expressing adenovirus variant, in which the telomerase promoter regulates viral replication (OBP-401), to selectively label human tumor cell with fluorescence. Whole blood cells collected from 7.5ml of peripheral blood were infected OBP-401 after elimination of anti-adenovirus antibodies and incubated at 37 oC. Viruses were inactivated 24 hours after virus-infection and then red blood cells were lysed. The GFP-expressing cells were detected using fluorescence microscopy.
Results: A total of 72 blood samples from 39 patients with histologically-confirmed gastric cancer (stage IA to IV) were analyzed. CTCs were detected in 32 of 39 patients (82%, range 1 to 40&lt;) before treatment, however, there was no apparent relationship between the number of CTCs and clinical status. We further assessed the CTC dynamics in 24 patients who were undergoing surgery, chemotherapy or endoscopic submucosal dissection (ESD). In patients with early gastric cancer, 7 patients had decrease in CTC numbers after surgery or ESD, and 6 patients had decreased CTC numbers following temporary increase after treatment. As for advanced cancer, the number of CTCs dropped in 3 patients after complete resection and increased in 2 patients with poor prognosis despite chemotherapy.
Conclusion: Our data suggest that patients with early gastric cancer also have CTCs in peripheral blood and the dynamic change of CTCs correlate with treatment response. Although numerous samples and long-term outcome should be analyzed, the enumeration of CTC using this GFP-expressing virus-based method might be useful for monitoring the efficacy of treatment.
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 3160. doi:10.1158/1538-7445.AM2011-3160
Abstract 318: Hierarchical clustering analysis of array CGH data identifies clinicopathologically distinct groups of lymph-node-negative invasive breast cancer
Authors: Kikuchi Ryoko , Ishii Yasuyuki , Kobayashi Takayuki , Kanai Yae , Shibata Tatsuhiro , Matsubara Osamu , Imoto Issei , Inazawa Johji , Tsuda Hitoshi 
Published: June 2012

Abstract
If high-risk group of lymph node-negative (pN0) invasive breast cancer is accurately identified by a molecular diagnosis of biopsy or surgically resected tumor specimens, it would be beneficial for choosing the most appropriate adjuvant or neoadjuvant therapies.
In this study, we examined genomic copy-number alterations of the 800 cancer-related genes in 51 pN0 primary invasive breast cancers (20 relapsed and 31 non-relapsed cases) surgically resected from 51 patients at the NCCH, Tokyo, between 1990 and 1994. DNA isolated from acetone-fixed paraffin-embedded tissues using microdissection were labeled directly with fluorescence dyes and subjected to array-based comparative genomic hybridizaton (array-CGH). Although copy number differences between relapsed and non-relapsed cases were unclear, unsupervised hierarchical clustering analysis was by using these 800 cancer-related genes resulted in identification of three cluster groups with significant differences in clinical outcome. Group 1 was mostly (9 of 13) composed ER(−)/HER2(−) cases, group 2 comprised 9 ER(+)/HER2(−), 8 ER(+)/HER2(+), and 6 ER(−)/HER2(+) cases, and group 3 was mostly (12 of 15) composed of ER(+)/HER2(−) cases. By the log-rank test for overall survival (OS), group 1 showed significantly worse outcome than group 2 (p = 0.0138), but no significant difference was observed in relapse-free survival (RFS) between these groups (p = 0.17). Among 20 patients who suffered relapsed later, both OS and RFS rates of group 1 were significantly higher than those of group 2 (p = 0.0083 and 0.0018). Representative genes that amplified in group 1 were CCND2(12p13.32), CDKN1B(12p13.1), whereas those kind genes in group 2 were ERBB2(17q12), NGFR(17q21.33).
This work demonstrates that hierarchical clustering of array-CGH data by using 800 cancer related genes can classify pN0 invasive breast cancers into clinically relevant groups and might pave the way to develop a new tool to estimate the risk of relapse and death in patients with pN0 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 318. doi:10.1158/1538-7445.AM2011-318
Abstract 3181: The combined use of urine and serum biomarkers in early detection strategies for pancreatic cancer
Authors: Nolen Brian M. , Lomakin Aleksey , Grizzle William E. , Jhala Nirag , Eloubeidi Mohamad A. , Christein John D. , Arnoletti Juan P. , Oelschlager Denise K. , Vickers Selwyn M. , Lokshin Anna E. 
Published: June 2012

Abstract
The devastatingly high level of mortality associated with pancreatic ductal adenocarcinoma (PDAC), the fourth leading cause of cancer death in the United States, has remained virtually unchanged over the past 50 years due to an inability to effectively detect and treat the disease at an early stage. Currently used imaging techniques including CT and MRI have demonstrated an inability to distinguish benign from malignant pancreatic lesions resulting in both a low sensitivity for pancreatic cancer and a high degree of unnecessary referral for highly invasive endoscopic ultrasound (EUS). A biomarker-based test that could effectively rule out the possibility of malignancy in patients presenting with an abnormal finding by CT or MRI would greatly reduce the number of unnecessary EUS procedure and the associated risk of complication as well as lead to an optimization of resources for more effective early detection of the disease. Serum biomarkers such as CA 19-9 have been under investigation in pancreatic cancer for a number of years. Recently, the use of urine in biomarker studies has garnered considerable interest based on its ease of sampling, high stability, and relative simplicity as a testing matrix. In order to evaluate the use of urine and serum biomarkers in pancreatic cancer screening, we analyzed 77 cancer-associated biomarkers in urine obtained from 55 patients diagnosed with PDAC and 44 patients diagnosed with benign pancreatic conditions. Twenty of the most relevant biomarkers were also tested in sera obtained from the same patient cohort. Forty of the 77 urine biomarkers as well as nine of the twenty serum biomarkers were significantly altered between the benign and malignant groups. Of the twenty biomarkers measured in both urine and serum, seven were more significantly altered in urine, while seven others were more significantly altered in serum. A multivariate analysis of the results identified a four-biomarker panel comprised of both serum and urine biomarkers which could discriminate PDAC from benign disease with optimal levels of sensitivity and specificity. Our results indicate a promising role for the combined use of urine and serum biomarkers in the development of improved screening strategies for pancreatic 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 3181. doi:10.1158/1538-7445.AM2011-3181
Abstract 3182: PTM ELISA microarray for breast cancer biomarker discovery
Authors: Jin Hongjun , Daly Don S. , Tan Ruimin , White Amanda M. , Marks Jeffrey R. , Zangar Richard C. 
Published: June 2012

Abstract
Post-translational modifications (PTMs) of proteins are known to be altered during breast cancer development. These PTMs are potentially useful biomarkers for breast cancer. In order to study the potential of PTMs in the early detection of breast cancer, ELISA microarray protocols for analyzing several PTMs in a panel of 24 proteins that are found in blood but known to be secreted by breast tissue and/or breast tumors. We evaluated these PTMs in a case-control study with 68 plasma samples. The control samples were from age-matched women with benign breast disease. The sensitivity and the specificity of each assay and the combined assays were evaluated using the areas under (AUC) the receiver operator curves. In the best multivariate analysis, the AUC values ranged from 77% to 87% for 4 different PTMs. Overall, our data suggest that the PTM ELISA microarray platform is a promising tool for discovery and evaluation of biomarkers that have potential for the early detection of 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 3182. doi:10.1158/1538-7445.AM2011-3182