bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2751: Automatic DNA extraction system can improve the EGFR point mutation detection rate of liquid biopsy
Authors: Nakashima Chiho , Sato Akemi , Abe Tomonori , Nakamura Tomomi , Komiya Kazutoshi , Sueoka Eisaburo , Kimura Shinya , Sueoka-Aragane Naoko , Kato Junichi , Hirai Mitsuharu 
Published: July 2017

Abstract
The usefulness of liquid biopsy to detect mutations from cancer patients has been well recognized today. However, because the mutation detection rates from plasma DNA were relatively lower than those of tissue re-biopsy, its clinical utility has not been confirmed yet. As previously we reported, we have developed fully automatic high-sensitive point mutation detecting system named mutation-biased PCR and quenched probe (MBP-QP) system for liquid biopsy. Recently, the importance of pre-analytical procedures for plasma DNA anazysis has been highlighted. In this study, we examined whether the automatic DNA extraction system can improve the mutation detection rate in our MBP-QP system. Sixty-one plasma samples were obtained from advanced non-small cell lung cancer patients, and plasma DNA extraction was performed from 200μl plasma by manually (200-M), and 200μl (200-A), 1000μl (1000-A) plasma by automatically. We used silica membrane spin column system for manual DNA extraction, and magnet beads system for automatic DNA extraction procedure. The median DNA concentrations quantified by quantitative real-time PCR of 200-M, 200-A, 1000-A were 4.92, 6.00, 20.1 ng/mL plasma, respectively. In terms of the epidermal growth factor receptor (EGFR) L858R point mutation detection, the sensitivity of 200-M, 200-A, 1000-A were 36.6%, 58.5%, 77.5%, that of the specificity were 93.3%, 100%, 96.7%, and the concordance rates were 60.6%, 76.1%, 85.7%, respectively. The size distribution of automatically extracted plasma DNA represented two peaks characteristics at 170 bp and 5 kb. In this study, we indicate the automatic DNA extraction can improve mutation detection rates in plasma DNA.
Citation Format: Chiho Nakashima, Akemi Sato, Tomonori Abe, Tomomi Nakamura, Kazutoshi Komiya, Eisaburo Sueoka, Shinya Kimura, Naoko Sueoka-Aragane, Junichi Kato, Mitsuharu Hirai. Automatic DNA extraction system can improve the EGFR point mutation detection rate of liquid biopsy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2751. doi:10.1158/1538-7445.AM2017-2751
Abstract 2752: Liquid biopsy analysis of FGFR3 and PIK3CA hotspot mutations for disease surveillance in bladder cancer
Authors: Christensen Emil , Birkenkamp-Demtröder Karin , Nordentoft Iver , Høyer Søren , Keur Kirstin Van Der , Kessel Kim Van , Zwarthoff Ellen , Agerbæk Mads , Ørntoft Torben Falck , Jensen Jørgen Bjerggaard , Dyrskjøt Lars 
Published: July 2017

Abstract
Background: Disease surveillance in patients with bladder cancer is important for early diagnosis of progression and metastasis and for optimal therapeutic treatment.
Experimental procedures: Droplet digital PCR (ddPCR) assays were developed and tumour DNA from two patient cohorts was screened for FGFR3 and PIK3CA hotspot mutations. One cohort (NMIBC cohort) included 363 patients with non-muscle invasive bladder cancer (NMIBC). Another cohort (Cx cohort) included 468 patients with bladder cancer undergoing radical cystectomy. Urine supernatants (NMIBC cohort: n=216, Cx cohort: n=27) and plasma samples (NMIBC cohort: n=39, Cx cohort: n=27) from patients harbouring mutations were subsequently screened using ddPCR assays. Liquid biopsies were collected from 2003-2015 with up to 11.3 years of follow-up for the NMIBC cohort and from 1995-2009 with up to 13.5 years of follow-up for the Cx cohort.
Results and limitations: In total, 36% of the patients in the NMIBC cohort (129/363) and 11% of the patients in the Cx cohort (44/403) harboured at least one hotspot mutation in FGFR3 or PIK3CA. Screening of DNA from serial urine supernatants from the NMIBC cohort showed high levels of tumour DNA (tDNA) to be significantly associated with later disease progression (p=0.003). Furthermore, high levels of tDNA in preoperative urine supernatants and plasma samples were associated with recurrence in the Cx cohort (p=0.068 and p=0.016 respectively). A positive correlation between the levels of tDNA in urine and plasma was observed (corr.=0.6). The retrospective study design and the low volumes of plasma available for analysis were limitations of the study.
Conclusions: Increased levels of FGFR3 and PIK3CA mutated DNA in urine and plasma is indicative of later progression and metastasis in bladder cancer.
Citation Format: Emil Christensen, Karin Birkenkamp-Demtröder, Iver Nordentoft, Søren Høyer, Kirstin Van Der Keur, Kim Van Kessel, Ellen Zwarthoff, Mads Agerbæk, Torben Falck Ørntoft, Jørgen Bjerggaard Jensen, Lars Dyrskjøt. Liquid biopsy analysis of FGFR3 and PIK3CA hotspot mutations for disease surveillance in bladder cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2752. doi:10.1158/1538-7445.AM2017-2752
Abstract 2754: A novel liquid biopsy method for development of aptamer libraries that bind blood plasma exosomes from breast cancer patients
Authors: Domenyuk Valeriy , Levenberg Symon , Stark Adam , Miglarese Mark , Spetzler David 
Published: July 2017

Abstract
Improved technologies capable of characterizing system-wide changes associated with complex diseases will be required to be able to detect millions of proteins and their isoforms as well as multi-molecular complexes. We present a method for developing aptamer libraries using blood plasma exosomes that provides unprecedented system-wide coverage of native exosomal complexes. To train a naïve aptamer library toward cancer samples (positive selection), the library (~1013 biotinylated ssODN species) was incubated with plasma from individual cancer patients and aptamer-bound exosomes were isolated using polymer-based precipitation. Negative selection was performed by contacting the aptamer library with exosomes from donors without breast cancer and recovering unbound aptamers from the supernatant. In all, 12 libraries trained toward 12 individual breast cancer patients were used to probe additional samples. Exosome-bound aptamers were identified and quantified by Next Generation Sequencing (NGS) to build highly accurate signatures for cancer/healthy donor classification. Using these signatures, cancer patients’ binding profiles were easily distinguishable from controls. Interestingly, cancer-trained libraries did not distinguish any of the negative control samples from each other, indicating that the selection pressure for cancer was high and noise due to inherent inter-healthy donor heterogeneity was minimal. Full validation studies are ongoing. Aptamer libraries may ultimately be deployed as a minimally-invasive diagnostic adjunct in breast and other cancers.
Citation Format: Valeriy Domenyuk, Symon Levenberg, Adam Stark, Mark Miglarese, David Spetzler. A novel liquid biopsy method for development of aptamer libraries that bind blood plasma exosomes from breast cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2754. doi:10.1158/1538-7445.AM2017-2754
Abstract 2765: Psychosocial predictors of life satisfaction among married women with breast cancer
Authors: Asuzu Chioma , Efosa-Urhoghide Ngozi 
Published: July 2017

Abstract
Introduction: Breast cancer presents a challenge to the totality of a woman’s life. Correlates of life satisfaction among married women with breast cancer have not been very well explored. Purpose: This study seeks to determine the relationship that exists between life satisfaction with depression, cognitive emotional regulation, sexuality, self-concept, dejection, interpersonal conflict and social support among married women with breast cancer in Southwest Nigeria. It also seeks to ascertain which of these variables predict life satisfaction among the respondents.
Method: The variables in the study were assessed using modified standardized instruments which were revalidated for cultural suitability after ethical approvals were obtained in each of the 5 centres involved in the study. The instruments were given to breast cancer patients after informed consent to participate in the study have been obtained.
Result: The larger proportion {148 or 40.5%)} of the participants were in the age range of 46-55 years and 112 (30.7%) had stage III disease. Analysis of data showed that significant linear relationship exists between life satisfaction of married women with breast cancer and depression (r = .200**; p &lt; .001), self-concept (r = .306**; p &lt; .001), cognitive emotional regulation (r = .398**; p &lt; .001), dejection (r = .226**; p &lt; .001), interpersonal conflict (r = .352**; p &lt; .001), anxiety (r =.316**; p &lt; .001), sexuality (r =.305*; p &lt; .001) and social support (r = .534; p &lt; .001). There were also significant correlations among the independent variables.
Conclusion: Psychosocial factors are potent predictors of life satisfaction among married women with breast cancer. Based on the findings, it was recommended that psycho-social intervention based on the factors identified as causative agents of life satisfaction should be developed and implemented for married individuals.
Note: This abstract was not presented at the meeting.
Citation Format: Chioma Asuzu, Ngozi Efosa-Urhoghide. Psychosocial predictors of life satisfaction among married women with breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2765. doi:10.1158/1538-7445.AM2017-2765
Abstract 2770: Bcl-2 overexpression is a predictive biomarker for the combination of ABT-199 with chemotherapy in diffuse large B-cell lymphoma cell lines
Authors: McConnell Ian , Anderson Elyse , Yazbeck Victor 
Published: July 2017

Abstract
Diffuse Large B-Cell Lymphoma (DLBCL) is the most common subtype of Non-Hodgkin’s Lymphoma. The anti-apoptotic Bcl-2 protein is expressed in certain DLBCL subtypes such as “Double-Hit” where it mediates resistance to chemotherapy. ABT-199 is a BH3-mimetic that specifically targets Bcl-2, and has shown excellent clinical activity in several hematological malignancies. The anti-apoptotic protein Mcl-1 mediates resistance to ABT-199, and can be inhibited with chemotherapy. However, despite variability in the Bcl-2 expression levels, current clinical trials involving combinations of ABT-199 and chemotherapy for the treatment of patients with DLBCL use a one-size-fits-all approach regardless of Bcl-2 expression levels. We hypothesized that high Bcl-2 expression levels correlates with sensitivity to the combination of ABT-199 and chemotherapy in DLBCL. We examined the activity of ABT-199 in four DLBCL cell lines with varying Bcl-2 levels (CARNAVAL, OCI-ly18, SU-DHL-4 and SU-DHL-8) as determined by cell viability (Cell Titer Glo Assay) and apoptosis (Annexin-V/PI staining and FACS) analyses. CARNAVAL and SU-DHL-8 have the highest and lowest Bcl-2 expression levels, respectively, as revealed by immunoblotting. Of the four cell lines, CARNAVAL displayed the highest sensitivity (IC50 = ~7 nM) while SU-DHL-8 was resistant (IC50 = &gt;10 µM) with the other 2 cell lines exhibiting intermediate sensitivity (45.9 nM for OCI-ly18 and 2.6 µM for SU-DHL-4). We then selected CARNAVAL and SU-DHL-8 in order to further examine the effect of the combination of ABT-199 with classic chemotherapy agents (etoposide and doxorubicin) used in DLBCL treatment. In CARNAVAL cells, the combination of either chemotherapy with ABT-199 led to a significant decrease in cell viability at 48 hrs compared to each single agent alone. This was associated with apoptosis induction as measured by Annexin-V/PI, caspase-3 and PARP cleavage, an increase in γ-H2AX (associated with DNA damage), and decrease in Mcl-1. Unlike CARNAVAL cells, ABT-199 did not enhance the activity of chemotherapy in SU-DHL-8 cells that lack Bcl-2 expression. These preclinical results support the use of Bcl-2 overexpression as a predictive biomarker for selecting patients that are likely to benefit from the combination of ABT-199 with chemotherapy in DLBCL. Current efforts are investigating the mechanism of resistance to the combination.
Citation Format: Ian McConnell, Elyse Anderson, Victor Yazbeck. Bcl-2 overexpression is a predictive biomarker for the combination of ABT-199 with chemotherapy in diffuse large B-cell lymphoma cell lines [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2770. doi:10.1158/1538-7445.AM2017-2770
Abstract 2781: Exosomal Del-1 as a potent diagnostic marker for breast cancer: A prospective cohort study
Authors: Lee Soo Jung , Lee Jeeyeon , Chae Yee Soo , Jung Jin Hyang , park Ho Yong , Baek Moon-Chang , Moon Pyong-Gon 
Published: July 2017

Abstract
Background: We previously demonstrated a diagnostic role of exosomal del-1 with two separated groups of breast cancer patients. In the current study, therefore, we aimed to confirm the diagnostic role in a prospective study with breast cancer by measuring plasma exosomal del-1 before and after surgery.
Patients and methods: To identify the optimal time of sampling after surgery, serial blood at day 1, 3, 5, and 7 after surgery was collected from 22 patients with early breast cancer. Thereafter, One hundred fifteen patients with breast cancer who underwent curative surgery were enrolled in the prospective cohort study to compare difference in plasma exosomal del-1 measured by ELISA at the time of diagnosis and post-surgery.
Results: Among all 22 patients for optimal sampling time after surgery, exosomal del-1 was higher than 0.5 at the time of diagnosis and then normalized at POD1. Among 115 patients for the confirmatory set, 109 (94.8%) patients showed a normalization of del-1 lower than 0.5 after surgery and 10 patients showed del-1&gt; 0.4 . Median f/u duration of 22 months, 9 patients experienced relapse (4 locoregional and 5 distant), where 3 out of 6 in high group (&gt;0.5), and 2 out of 4 in borderline group (0.4-0.5), and 4 out of 105 in normalized group (&lt;0.4). In particular, patients who relapsed in higher del-1 group showed relatively earlier relapse compared to lower del-1 group.
Conclusion: In a prospective cohort study, we confirmed that exosomal del-1 has a potent diagnostic role in breast cancer. Furthermore, del-1 was also identified to dramatically decrease after curative surgery. Our current findings suggest its potential prognostic role as well as diagnostic role in breast cancer patients.
Changes of Exosomal Del-1 level between baseline and after-surgery (n=115)sampling timebaselineafter surgeryp-value(paired t-test)Del-1 (mean±SD)1.237±0.4530.188±0.124&lt;0.001
Citation Format: Soo Jung Lee, Jeeyeon Lee, Yee Soo Chae, Jin Hyang Jung, Ho Yong park, Moon-Chang Baek, Pyong-Gon Moon. Exosomal Del-1 as a potent diagnostic marker for breast cancer: A prospective cohort study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2781. doi:10.1158/1538-7445.AM2017-2781
Abstract 2797: MiR-137 and MiR-496 target Del-1 and affect triple negative breast cancer progression
Authors: Lee Jeeyeon , Chae Yee Soo , Lee Soo Jung , Jung Jin Hyang , Park Ho Yong , Baek Moon-Chang 
Published: July 2017

Abstract
Background: Although Del-1 was recently proposed as a new biomarker for early breast cancer in our previous studies, the mechanisms of Del-1 expression are barely understood. In the current study, we selected two microRNAs (miR-137 and - 496), potentially affecting Del-1 expression in breast cancer and examined their impact on Del-1 expression in a variety of breast cancer cell lines to identify their potential role in Del-1 expression and thereby breast cancer development or progression.
Methods: Del-1 mRNA and miR-137/- 496 levels were measured by qRT-PCR among breast epithelial (MCF10A) and cancer cells (MDA-MB-231, MCF7, SK-BR3 and T-47D). The effects of miR-137/- 496 on cell proliferation and invasion were detected using MTT, wound healing and Transwell assays. Furthermore, luciferase reporter assay was used to identify the direct regulation of Del-1 by miR-137 or - 496 in MDA-MB-231 cells. Plus, we analyzed the expressions of miR-137 or - 496 and Del-1 mRNA from 20 patients with triple negative early breast cancer.
Results: miR-137 and - 496 levels were low in all breast cancer cell lines. As Del-1 mRNA expression was remarkably higher in MDA-MB-231 compared to the other breast cancer cell lines, further functional analyses were done with MDA-MB-231 representing triple negative breast cancer subtype. Both miR-137 and miR-496 were revealed to directly bind at the 3’-UTR of Del-1. Del-1 by Luciferase reporter assay and Del-1 expression was upregulated by inhibitors and reversed by both mimics of both miR-137 and miR-496. Furthermore, both miR-137 and miR-496 were also demonstrated to inhibit cell proliferation, migration and invasion of MDA-MB-231, suggesting that these miRNAs affect cancer progression via Del-1. MiR-137 and miR-496 were remarkably down-regulated in 7 out of 12 triple negative breast cancer tissues, in particular with high Ki67 and high histologic grade.
Conclusion: Although Del-1 was recently introduced as a new biomarker for triple negative breast cancer, the mechanisms of Del-1 expression were barely identified. The current study firstly demonstrated that microRNA 137 and 496 are involved in Del-1 regulation by binding at Del-1 gene, affecting cancer progression by altering Del-1 expression.
Citation Format: Jeeyeon Lee, Yee Soo Chae, Soo Jung Lee, Jin Hyang Jung, Ho Yong Park, Moon-Chang Baek. MiR-137 and MiR-496 target Del-1 and affect triple negative breast cancer progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2797. doi:10.1158/1538-7445.AM2017-2797
Abstract 280: The maximum tumor length and lymph node metastasis in esophageal squamous cell carcinomas
Authors: Lv Shuang , Lv Shuang , Zhou Fu You , Yang Hai Jun , Li Bei , Liu Li Na , Xia Yan Jie , Qin Yan Ru , Fan Rui Tai , Xiao Fan Kai , Wang Li Dong 
Published: July 2017

Abstract
The lymph node metastasis (LNM) is one of the crucial risk factors for esophageal squamous cell carcinomas (ESCC) prognosis. However, it is difficult to precisely determine the LNM status before surgery. The maximum tumor length (MTL) may reflect the ESCC growth speed and could be calculated accurately either with computed tomography or ultrasound endoscopy before esophagectomy. Therefore the present study was designed to determine if the MTL could reflect the LNM status for ESCC. A total of 22,660 ESCC patients was enrolled in this study from the ESCC database (1973-2015) in Henan Key Laboratory for Esophageal Cancer Research of the First Affiliated Hospital, Zhengzhou University. Of these patients, there were 13,793 males with an mean age of 60±8, and 8,867 females with an mean age of 61±8. All the cases had been performed radical esophagectomy. The MTL and LNM records were retrieved from the medical records in hospitals. Based on the 6th version of UICC criteria, the LNM was classified as N0 and N1. The MTL was classified as 5 groups: &lt;2cm, ≥2 and &lt;4cm, ≥4 and &lt;6cm , ≥6 and &lt;8cm , ≥8cm. The SPSS21.0 software and Spearman rank correlation were used to determine the correlation of MTL and LNM. The results demonstrated that the average and median of MTL were 4.1±1.8 cm and 4.0 cm (range: 0.1-18 cm) in these ESCC patients. The positive lymph node metastasis rates in each MTL groups were 19.1%, 34.1%, 45.8%, 51.5%, and 54.1%, respectively. Spearman rank correlation analysis indicated that MTL was strongly correlated with LNM (r=0.997, P&lt;0.001), suggesting that MTL could reflect the LNM status in ESCC and that MTL could be used as one of clinical staging parameters for ESCC. [Supported by Major Science and Technology Projects of Henan Province (161100311300). National Key Research and Development Program: Precision Medicine (2016).]
Note: This abstract was not presented at the meeting.
Citation Format: Shuang Lv, Shuang Lv, Fu You Zhou, Hai Jun Yang, Bei Li, Li Na Liu, Yan Jie Xia, Yan Ru Qin, Rui Tai Fan, Fan Kai Xiao, Li Dong Wang. The maximum tumor length and lymph node metastasis in esophageal squamous cell carcinomas [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 280. doi:10.1158/1538-7445.AM2017-280