bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3473: Intra-person and inter-person biomarker variation for modeling longitudinal values of ovarian cancer early detection biomarkers.
Authors: Raamanathan Archana , Lu Zhen , Bast Robert C. , Skates Steven J. 
Published: August 2014

Abstract
In 2012, an estimated 22,280 women will be diagnosed with ovarian cancer in the United States and 15,500 women will die from this disease. Though localized ovarian cancers have a survival rate of 92%, only 15-20% of ovarian cancers are detected at this stage. Developing an effective strategy for early detection could reduce mortality. While individual values of CA125 are neither sufficiently sensitive nor specific for early detection, monitoring CA125 over time shows greater specificity. The risk of ovarian cancer algorithm, ROCA, analyzes the trend of annual values for CA125, utilizing each woman's own baseline to refer a small fraction (&lt;1-2%) of women to transvaginal sonography. Using this strategy, no more than three operations are required for each case of ovarian cancer detected. Use of multiple biomarkers might increase sensitivity for preclinical disease. Based on a multiplex assay of 96 biomarkers, a four biomarker panel was identified of CA125, HE4, MMP-7 and CA 72-4 with greater sensitivity than CA125 alone. To estimate the utility of these biomarkers for longitudinal screening, we assessed five annual longitudinal control serum samples from 200 women who did not develop ovarian cancer from the MDACC SPORE normal risk ovarian cancer screening study (NROSS). Utilizing WinBUGS, the inter-person and intra-person CVs were evaluated. Upon log transformation for CA125, HE4 and MMP-7 and log(log()+1) transformation for CA72-4, both the inter-person and intra-person CVs follow a log-normal distribution. The median inter-person CVs for CA125, HE4, MMP-7 and CA 72-4 were 49%, 20%, 35% and 84% respectively and the median intra-person CVs were 15%, 25%, 21% and 21% respectively. The ratios of intra-person CVs to inter-person CVs derived for CA125, HE4, MMP-7 and log(CA 72-4) were 0.31, 1.25, 0.6 and 0.31. We anticipate that the lower the ratio, the higher the contribution of each individual marker to early detection during longitudinal measurements. The intra-person CV's should permit development of a multi-marker algorithm. Assessment of longitudinal samples derived from 50 cases of preclinical ovarian cancer and 10 controls per case (UKCTOCS trial) are underway in order to establish such a longitudinal multi-marker algorithm for assessment of ovarian cancer risk.
Citation Format: Archana Raamanathan, Zhen Lu, Robert C. Bast, Steven J. Skates. Intra-person and inter-person biomarker variation for modeling longitudinal values of ovarian cancer early detection biomarkers. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3473. doi:10.1158/1538-7445.AM2013-3473
Abstract 3474: GDF15 as a serum marker of cisplatin response in ovarian cancer cells.
Authors: Izaguirre Daisy I. , Kwan Suet Yan , Zu Zhifei , Tsang-Lee Yvonne T. , Wong Kwong-Kwok 
Published: August 2014

Abstract
Ovarian cancer treatment consists of surgery followed by a chemotherapy combination entailing a platinum agent (cisplatin/carboplatin) and a taxane (paclitaxel). While 70-80% of patients initially respond to the standard treatment, the majority will relapse, and of these patients, 70-90% die because of drug resistance. Therefore, identifying markers that can predict therapeutic response and/or therapeutic targets is of great interest. To identify genes involved in chemoresistance, a microarray study of an ovarian cancer cell line (A2780) treated with varying doses of cisplatin and at varying time points was conducted. This study showed GDF15 had the highest fold-induction by cisplatin treatment. GDF15 induction by cisplatin was further validated by RT-PCR and Western blot analysis in the A2780 and 12 other cell lines with varying sensitivity/resistance to cisplatin. To further test whether GDF15 plays a role in cisplatin resistance, we knocked down its expression by esiRNA. GDF15 knockdown revealed an increase in the cisplatin IC50, suggesting that GDF15 sensitizes ovarian cancer cells to cisplatin. To determine whether GDF15 was also induced in vivo we injected mice intraperitoneally with either A2780 (cisplatin sensitive) or RMG1 (cisplatin resistant) cells. Once the tumors developed, the mice were treated with either 2.5 mg/kg or 5 mg/kg cisplatin and both the tumors and sera collected 24 and 48 hours after treatment. ELISA results on the serum showed an increase in GDF15 in mice after cisplatin treatment. Although there was no correlation between the two cisplatin doses used and GDF15 there was a correlation between GDF15 and tumor weight. Thus, our results suggest that GDF15 is induced by cisplatin both in vitro and in vivo and has a potential role as a serum biomarker to predict chemotherapeutic response.
Citation Format: Daisy I. Izaguirre, Suet Yan Kwan, Zhifei Zu, Yvonne T. Tsang-Lee, Kwong-Kwok Wong. GDF15 as a serum marker of cisplatin response in ovarian cancer cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3474. doi:10.1158/1538-7445.AM2013-3474
Abstract 348: LKB1 deficiency confers lung adenocarcinoma phenotypic plasticity with squamous transdifferentiation potential.
Authors: Han Xiangkun , Li Fuming , Fang Zhaoyuan , Gao Yijun , Fang Rong , Li Fei , Sun Yihua , Xia Jufeng , Yao Shun , Li Li , Chen Haiquan , Hou Yingyong , Liu Xinyuan , Ji Hongbin 
Published: August 2014

Abstract
The existence and related mechanisms of phenotypic plasticity and dynamic lineage conversion of lung cancers, as implicated by clinical observation of mixed adenocarcinoma (ADC) and squamous cell carcinoma (SCC) pathologies in adenosquamous cell carcinoma (Ad-SCC), remain as fundamental yet unsolved questions. Here we find that about 13% human lung Ad-SCC harbor genetic alterations of tumor suppressor LKB1. Through lineage tracing experiments and pathological analyses in mouse models of human lung cancer, we further show that LKB1 deficiency confers lung adenocarcinoma phenotypic plasticity to progressively transdifferentiate into squamous cell carcinoma (SCC), via pathologically mixed Ad-SCC as intermediate. Down-regulation of lysyl oxidase (LOX) following reduced hypoxia level in LKB1-deficient lung adenocarcinoma decreases collagen disposition and triggers extracellular matrix remodeling and eventually up-regulates p63 expression, the SCC lineage survival oncogene. Moreover, pharmacological inhibition of Lox enzymatic activity promotes the transdifferentiation, whereas ectopic Lox expression conversely increases collagen deposition and significantly inhibits this process. ADC and SCC show differential response to pharmacological Lox inhibition. Notably, human lung Ad-SCC with LKB1 genetic alterations show pathology-specific patterns of LOX expression and collagen deposition in adenomatous and squamous portions as seen from animal models. These data uncover an essential role and related molecular mechanism of LKB1 deficiency in determining lung adenocarcinoma phenotypic plasticity.
Citation Format: Xiangkun Han, Fuming Li, Zhaoyuan Fang, Yijun Gao, Rong Fang, Fei Li, Yihua Sun, Jufeng Xia, Shun Yao, Li Li, Haiquan Chen, Yingyong Hou, Xinyuan Liu, Hongbin Ji. LKB1 deficiency confers lung adenocarcinoma phenotypic plasticity with squamous transdifferentiation potential. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 348. doi:10.1158/1538-7445.AM2013-348
Abstract 3481: Development of personalized paclitaxel therapy (IG-001) for ovarian cancer.
Authors: Hwang Larn , Hsiao Chao , Motamed Kouros , Trieu Vuong 
Published: August 2014

Abstract
Introduction: IG-001, like nab-paclitaxel, is a polymer bound nanoparticle paclitaxel. It is being developed for difficult to perfuse hypoxic tumors such as pancreatic cancer and ovarian cancer. IG-001 has shown promising activity against ovarian cancer in phase II clinical trials. In the planned phase III trial of IG-001, serum biomarkers as well as blood paclitaxel will be monitored to as prognostic indicators of response. The goal of this study is to developed point-of-care testing devices for PD biomarkers including CA125, B-type natriuretic peptide (BNP), Follicle Stimulating Hormone (FSH) and blood paclitaxel.
Methods: Serum samples collected at time of diagnosis of ovarian cancer were tested using rapid and quantitative point-of-care (POC) devices for blood biomarkers (CA125, FSH, BNP, and paclitaxel) and the data were evaluated using JMP9 statistical analysis software.
Results: 41 ovarian cancer patients were analyzed for CA125 prior to surgery of which 3 (7%), 11 (27%), and 27 (66%) were clear cell carcinoma, cystadenocarcinoma and adenocarcinoma, respectively. CA125 was not diagnostic of ovarian cancer. However, incidence of elevated (BNP &gt; 25 pg/ml) was higher for patients (14 of 19, 74%) vs. normal controls (3 of 10, 30%, p = 0.02, Chi-square). FSH level was higher (median=151.6 mU/ml) vs. normal controls (median of 13.4 mU/ml, p = 0.01, Wilcoxon). Paclitaxel POC device was developed to monitored paclitaxel level down to 20ng/mL for paclitaxel.
Conclusions: Rapid and quantitative point-of-care tests for PD biomarker testing and paclitaxel PK therapeutic drug monitoring have been developed for use in conjunction with IG-001 development against ovarian cancer. IG-001 is ideal for paclitaxel therapeutic drug monitoring (TDM) due to its dose proportional PK. Paclitaxel TDM should allow for more effective dosing of the patients and thereby improving effectiveness of IG-001. These POCTs are also patient-centric, inviting better compliance and patient participation in personalizing his/her treatment. Plasma or serum samples obtained via repetitive venipuncture represent the accepted gold standard for monitoring the pharmacodynamics (PD) and pharmacokinetics (PK) of anticancer agents. Unfortunately for research subjects, the burden of frequent venipuncture is high; and, for researchers, venipuncture samples require immediate processing and storage facilities with freezers. The work presented here resolved the operational difficulty associated with personalized therapy in general and IG-001 in specific.
Citation Format: Larn Hwang, Chao Hsiao, Kouros Motamed, Vuong Trieu. Development of personalized paclitaxel therapy (IG-001) for ovarian cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3481. doi:10.1158/1538-7445.AM2013-3481
Abstract 3482: Directly Detect High Risk HPV Oncogenes E6/E7 mRNAs from Pap Smear Samples without RNA Purification and RT-PCR.
Authors: Zhang Aiguo , Zhang Lulu , Chuang Rachel , Zhu Xining , Diaz Rachel , Chen Lily 
Published: August 2014

Abstract
Cervical cancer is one of the most common cancers in women, with about 450,000 new cases diagnosed each year. Nearly all the cervical cancers are from Papillomaviruses (HPV) infection. HPV are DNA-based viruses that infect the skin and mucous membranes of humans and many other animals. Most cancers of the vulva and vagina are induced by oncogenic HPV types. In precancerous lesions, most HPV genomes persist in an episomal state whereas, in many high-grade lesions and carcinomas, genomes are found integrated into the host chromosome. Two viral genes, E6 and E7, are invariably expressed in HPV-positive cancer cells. Their gene products are known to inactivate the major tumour suppressors, p53 and retinoblastoma protein (pRB), respectively. In addition, E6 oncoprotein is also capable to up regulate the expression of inhibitors of apoptosis, and E6 and E7 cooperate to effectively immortalise primary epithelial cells. It has been demonstrated that HPV E6/E7 expression level plays a key role in the progression of invasive carcinoma of the uterine cervix via the deregulation of cellular genes controlling tumour cell proliferation. HPV E6/E7 oncogenes have been proved to be good biological markers for prognosis assessment and specific therapy of the disease. We have developed a sandwich nucleic acid hybridization assay using branched DNA to amplify the signals. The assay can simultaneously detect E6/E7 mRNAs of all 14 high risk HPV subtypes directly from Pap smear samples without RNA purification and RT-PCR. All HPV mRNA targets are captured through cooperative hybridization of multiple probes and probe set design determines the specificity of each HPV subtype of E6/E7 mRNA. Probe set oligonucleotides bind a contiguous region of the target E6/E7 mRNAs and selectively capture target RNAs to a solid surface during hybridization. Signal amplification is performed via sequential hybridization of Pre-Amplifier, Amplifier and label probe. The assay is highly specific and sensitive, which can detect as low as 50 transcript molecules.
Citation Format: Aiguo Zhang, Lulu Zhang, Rachel Chuang, Xining Zhu, Rachel Diaz, Lily Chen. Directly Detect High Risk HPV Oncogenes E6/E7 mRNAs from Pap Smear Samples without RNA Purification and RT-PCR. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3482. doi:10.1158/1538-7445.AM2013-3482
Abstract 3483: Modeling circulating tumor cells in the peripheral blood and CSF of breast cancer patients.
Authors: Allen Joshua E. , Patel Akshal S. , Dicker David T. , Sheehan Jonas M. , Glantz Michael , El-Deiry Wafik S. 
Published: August 2014

Abstract
The enumeration of circulating tumor cells (CTCs) using the CellSearch system (Veridex LLC) is a valuable prognostic clinical tool in several epithelial malignancies. Surveillance methods for metastatic disease involving the central nervous system (CNS) lack adequate sensitivity, specificity, and reproducibility in the clinic. We previously reported a method to enumerate CTCs in the cerebrospinal fluid (CSF) of breast cancer patients with metastases involving the CNS. The enumeration of CTCs in CSF by this method is highly sensitive, accurate, reproducible, and correlates with disease burden by several measures. Here, we concomitantly monitor CTCs in the peripheral blood and CSF of five patients with neoplastic meningitis receiving intrathecal (IT) chemotherapy. In each patient, CTC counts have been more sensitive than conventional cytology, and have predicted the course of symptoms and overall survival more precisely than conventional cytology. We observed a striking inverse relationship between CTC counts in the peripheral blood and CSF. This observation generated the hypothesis that CTCs migrate from the blood to the CSF and the converse as sanctuary sites during compartmentalized therapy to result in systemic disease recurrence. To test this hypothesis we created mouse models of these clinical phenomena including injection of triple-negative breast cancer into the peripheral blood or intracranially. Injection of luciferase-infected MDA-MB-231 or MDA-MB-468 human triple-negative breast cancer cells into the brain of athymic nude mice resulted in primary tumors at the site of injection. The MDA-MB-231, unlike the MDA-MB-468, generated detectable tumor cell dissemination into the CSF of inoculated mice that correlated with a significantly declined survival. CSF collected from the cisterna magna of inoculated mice corroborated these observations. Current studies are examining the impact of compartmentalized therapy on the migration of these tumor cells as well as profiling unique genetic drivers of the subset of tumors cells that disseminate into the CSF. The intercompartmental cycling of tumor cells may represent an important mechanism for disease persistence and recurrence, and suggests that concurrent systemic and CNS-directed therapy may be warranted.
Citation Format: Joshua E. Allen, Akshal S. Patel, David T. Dicker, Jonas M. Sheehan, Michael Glantz, Wafik S. El-Deiry. Modeling circulating tumor cells in the peripheral blood and CSF of breast cancer patients. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3483. doi:10.1158/1538-7445.AM2013-3483
Abstract 3489: A novel monoclonal antibody to native HER2 epitope detects HER2-positive CTCs, HER2 in blood, and HER2 in tissue: realistic approach for monitoring breast carcinoma.
Authors: Alper Özge , Akoa Achille , Alper Özgül M. , Chen Cui P. 
Published: August 2014

Abstract
Background: Amplification of the HER2 gene and/or overexpression of its protein product have been reported in 25% to 30% of breast carcinomas and have been associated with poorer outcomes. However, there are still highly controversial aspects of HER2 testing. In the present study, we generated a novel monoclonal antibody against human native epitope of HER2 and investigated its clinical potential in managing breast carcinoma.
Methods and findings: We generated a novel monoclonal antibody (mAb), AB-HER2 using hybridoma technology and native folding of the protein as an immunogen. This mAb is of IgG1 (kappa) type. It specifically recognized both native and denatured human HER2 protein and displayed high affinity as assessed by Circulating Tumor Cells (CTCs), ELISA, immunohistochemistry assay, western blot and flow cytometry applications. We have developed a CTCs assay to detect specific HER2-positive tumor cells circulating in blood, while we did not observe any background staining in blood cells. Using AB-HER2 mAb in ELISA, we showed soluble HER2 level is significantly increased in breast cancer patients’ plasma which directly correlated with HER2 expression pattern in breast cancer tissues. Tissue expression of HER2 was determined by using immunohistochemical techniques. Most of normal tissues showed negative staining, while different levels of membrane staining were observed in cancer sections. To evaluate the immunoreactivity of HER2 associated with tumor histological types, the staining intensity in membranes were scored according to the guidelines of ASCO/CAP. We also have compared AB-HER2 mAB with commercial HER2 antibodies in all immunoassays.
Conclusion: The novel AB-HER2 mAb showed improved accuracy in all immunoassays and clinical outcome. Circulating HER2-positive tumor cells, HER2 protein levels in plasma and in breast tissues significantly increased in patients with breast carcinoma compared to normal healthy controls. Our data suggest the potential clinical use of AB-HER2 mAB as a powerful immunoreagent in measuring real-time HER2 levels in managing breast cancer.
Citation Format: Özge Alper, Achille Akoa, Özgül M. Alper, Cui P. Chen. A novel monoclonal antibody to native HER2 epitope detects HER2-positive CTCs, HER2 in blood, and HER2 in tissue: realistic approach for monitoring breast carcinoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3489. doi:10.1158/1538-7445.AM2013-3489
Abstract 3500: Analysis of the prevalence and prognostic significance of 92 endpoints using high throughput multiplexed qPCR In archival tissue from multiple NSCLC trials.
Authors: Do An D. , Sumiyoshi Teiko , Wang Yulei , Schleifman Erica , Xiao Yuanyuan , Klughammer Barbara , Wong Cheryl V. , Abbas Ilma , Fu Ling , Amler Lukas C. , Raja Rajiv , Shames David S. 
Published: August 2014

Abstract
Over one third of all cancer related deaths worldwide are caused by non-small cell lung cancer (NSCLC). Until recently, tumor histology was rarely a factor in treatment decisions. However, this paradigm is shifting with the recent emergence of molecularly targeted therapies and next-generation chemotherapies. To better define the molecular sub-types of NSCLC that associate with active therapies and to evaluate their prognostic significance in historical clinical trials, we developed a microfluidics-based multiplexed PCR platform that enables analyses of 96 gene transcripts in 96 samples using material from as little as a single biopsy slide. The multiplexed assay panel consists of Taqman assays for markers of histology, chemo-resistance, prognosis, oncogenic pathway activity, epithelial vs. mesenchymal biology, as well as NSCLC drug targets.
We report here on the development and validation of this 96-gene transcript-profiling panel. Using titrations of several lung biopsy formalin-fixed paraffin embedded (FFPE) tissues, we show that as little as 10 ng of FFPE RNA is feasible and yields robust gene expression data across all assays of the profiling panel.
Using this technology, we tested archival lung biopsy samples from multiple Phase II and III studies to assess the prevalence and potential prognostic significance of 92 endpoints in parallel. We identified several markers that were strongly associated with histology as defined by TTF1 or p63 expression. In addition, several of the these markers were also associated with longer survival regardless of therapy, and will be discussed. These data suggest that retrospective analyses of clinical trial samples using Fluidigm-based expression analysis can be used to better inform future trial design in NSCLC.
Citation Format: An D. Do, Teiko Sumiyoshi, Yulei Wang, Erica Schleifman, Yuanyuan Xiao, Barbara Klughammer, Cheryl V. Wong, Ilma Abbas, Ling Fu, Lukas C. Amler, Rajiv Raja, David S. Shames. Analysis of the prevalence and prognostic significance of 92 endpoints using high throughput multiplexed qPCR In archival tissue from multiple NSCLC trials. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3500. doi:10.1158/1538-7445.AM2013-3500