bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4737: A lung cancer risk classifier comprising genome maintenance genes measured in normal bronchial epithelial cells
Authors: Yeo Jiyoun , Crawford Erin , Zhang Xiaolu , Khuder Sadik , Chen Tian , Levin Albert , Blomquist Thomas , Willey James 
Published: July 2017

Abstract
Background: Annual low dose CT (LDCT) screening of individuals at high demographic risk reduces lung cancer mortality by more than 20%. However, subjects selected for screening based on demographic criteria typically have less than a 10% lifetime risk for lung cancer. Thus, there is need for a biomarker that better stratifies subjects for LDCT screening. Toward this goal, we previously reported a lung cancer risk test (LCRT) biomarker comprising 14 genome-maintenance (GM) pathway genes measured in normal bronchial epithelial cells (NBEC) that accurately classified cancer (CA) from non-cancer (NC) subjects. The primary goal of the studies reported here was to optimize the LCRT biomarker for high specificity and ease of clinical implementation.
Methods: Targeted competitive multiplex PCR amplicon libraries were prepared for next generation sequencing (NGS) analysis of transcript abundance at 68 sites among 33 GM target genes in NBEC specimens collected from a retrospective cohort of 120 subjects, including 60 CA cases and 60 NC controls. Genes were selected for analysis based on contribution to the previously reported LCRT biomarker and/or prior evidence for association with lung cancer risk. Linear discriminant analysis was used to identify the most accurate classifier suitable to stratify subjects for screening.
Results: The best classifier comprised 11 features including age and 10 transcript abundance assays representing nine genes; specifically, CDKN1A, E2F1, ERCC5, GPX1, GSTP1, KEAP1, TP63, XPA, and XRCC1. After cross-validation, the Receiver Operator Characteristic area under the curve was 0.94 (95% CI: 0.92-0.96) and overall classification accuracy was 88.3% (95% CI 82.4%-94.1%). Using a threshold set at 95% sensitivity, specificity was &gt; 70%.
Conclusions: The LCRT biomarker reported here displayed high specificity and ease of implementation on a high throughput, quality-controlled targeted NGS platform. As such, it is optimized for clinical validation in specimens from the ongoing LCRT blinded prospective cohort study. Following validation, the biomarker is expected to have clinical utility by better stratifying subjects for annual lung cancer screening compared to current demographic criteria alone.
Citation Format: Jiyoun Yeo, Erin Crawford, Xiaolu Zhang, Sadik Khuder, Tian Chen, Albert Levin, Thomas Blomquist, James Willey. A lung cancer risk classifier comprising genome maintenance genes measured in normal bronchial epithelial cells [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 4737. doi:10.1158/1538-7445.AM2017-4737
Abstract 4743: Identification of metastasis-associated biomarker PLEC1 by iTRAQ-based proteomic approach and prognostic role of PLEC1 in patients with hepatocellular carcinoma
Authors: Song Lin-lan , Chen Yu , Mu Di , Jiang Xiao-Yan , Li Yu-Nong , Jiang Ling-Yu , Zhang Zhen-Fang , Yan Liang , Yang Min , Yang Yi-xuan , Ren Hong , Liao Yong 
Published: July 2017

Abstract
Purpose: Hepatocellular Carcinoma(HCC)is the fifth most prevalent cancer and the second most frequent cause of cancer-related death in men worldwide because of high incidence of recurrence and widespread metastasis. However, to date, there have been no direct metastesis-associated biomarker which is critical for the effective treatment of patients with HCC, we thus aimed to identify novel HCC metastasis-associated biomarkers with prognostic significance.E
xperimental Design: Two human HCC cell lines, MHCC97-L and MHCC97-H with similar genetic background and stepwise increasing metastatic potentials, were used to explore potential metastasis-associated biomarkers for HCC by isobaric tag for relative and absolute quantitation (iTRAQ) combination with 2D-LC-MS/MS. Ninety-five HCC cancerous and paracancerous tissues were further analyzed by immunohistochemistry to validate the correlations between the expression levels of PLEC1 with various clinicopathologic factors and patient survival.
Results: Using iTRAQ combination with 2D-LC-MS/MS, a total of 47 differentially expressed proteins were found in MHCC97-L and MHCC97-H cells, of which 26 proteins were up regulated and 21 proteins were down regulated. Plectin-1 (PLEC1) was identified and re-confirmed as a potential biomarker for HCC that was highly up-regulated in tumor tissues, in comparison with that of para-cancerous tissues. Over-expression of PLEC1 was also strongly correlated with tumor size (P &lt; 0.05) and TMN stages (P &lt; 0.05). In addition, both univariate and multivariate analyses demonstrate that PLEC1 expression is an independent prognostic factor for patients with HCC(p&lt;0.05).
Conclusions: In this study, iTRAQ-based proteomic technology was explored to uncover novel metastasis-associated biomarkers in HCC. We identified and validated metastasis-associated protein PLEC1 as a potential prognostic marker in patients with HCC.
Note: This abstract was not presented at the meeting.
Citation Format: Lin-lan Song, Yu Chen, Di Mu, Xiao-Yan Jiang, Yu-Nong Li, Ling-Yu Jiang, Zhen-Fang Zhang, Liang Yan, Min Yang, Yi-xuan Yang, Hong Ren, Yong Liao. Identification of metastasis-associated biomarker PLEC1 by iTRAQ-based proteomic approach and prognostic role of PLEC1 in patients with hepatocellular carcinoma [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 4743. doi:10.1158/1538-7445.AM2017-4743
Abstract 4748: Novel predictive biomarker for monitoring adverse reactions to radiation therapy
Authors: OKunieff Paul , Swarts Steven , Peletskya Elena , Vallerga Anne , Chuang Rachel , Powell Michael J. , Zhang Aiguo 
Published: July 2017

Abstract
Introduction: Radiation treatment is required by 70% of cancer patients, however there is currently no clinical method for determining the therapeutic response or radiation induced toxicity that can be used during a course of radiation therapy to personalize the dose for individual patients. The only standard method is CT/PET and/or MRI. This is a major clinical concern for radiation oncologists with so many new agents being approved in combination with radiation therapy.
Methodology: Herein we describe a highly sensitive clinically validated assay that measures the extent of normal tissue damage induced by radiation by quantitation of circulating free DNA (cfDNA) derived from cellular apoptosis detected in plasma of patients undergoing radiation therapy. The assay employs DNA capture probes and SuperbDNATM signal amplification technology with alkaline phosphatase labelled signaling probes coupled with dioxetane phosphate chemiluminescence detection. The assay can be performed directly on patient plasma samples and can be readily automated.
Conclusion: RadTox TM can be used both for research and clinical testing of plasma samples for patients undergoing radiation therapy for optimization and personalization of treatment.
Citation Format: Paul OKunieff, Steven Swarts, Elena Peletskya, Anne Vallerga, Rachel Chuang, Michael J. Powell, Aiguo Zhang. Novel predictive biomarker for monitoring adverse reactions to radiation therapy [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 4748. doi:10.1158/1538-7445.AM2017-4748
Abstract 475: Role of microRNA-34a in regulating oncoprotein STMN1
Authors: Chakravarthi Balabhadrapatruni V.S.K. , Mehra Rohit , Wang Rui , Chandrashekar Darshan Shimoga , Balasubramanya Sai Akshaya Hodigere , Asangani Irfan A. , Lonigro Robert J. , Chinnaiyan Arul M. , Varambally Sooryanarayana 
Published: July 2017

Abstract
MicroRNAs, as negative regulators of gene expression, play a major role in cellular homeostasis. Downregulation of miRs is common in cancer which results in upregulation of multiple oncogenes in cancer. Here we show that stathmin (STMN1), which is over-expressed and oncogenic in wide variety of cancers, is regulated by microRNA-34 in prostate cancer. Earlier studies suggest that stathmin is involved in vital cellular processes such as cell proliferation, motility and metastasis. In the present study, we show elevated expression of stathmin in metastatic prostate cancer. Functionally, knockdown of stathmin in prostate cancer cells resulted in reduced cell proliferation and invasion in vitro, and tumor growth and metastasis in vivo. We also show that tumor suppressor microRNA miR-34a targets stathmin and mir-34 is regulated by transcriptional corepressor CtBP1 (C-Terminal Binding Protein 1). Further, Microarray analyses using stathmin modulated prostate cancer cell line RNA revealed multiple molecular alterations which may play a critical role in STMN1-mediated oncogenic activity. Thus, our study suggests that CtBP1-regulated miR-34a modulates stathmin expression in prostate cancer. This study therefore demonstrates functional role of CtBP1-miR-34a-Stathmin axis in prostate cancer progression.
Citation Format: Balabhadrapatruni V.S.K. Chakravarthi, Rohit Mehra, Rui Wang, Darshan Shimoga Chandrashekar, Sai Akshaya Hodigere Balasubramanya, Irfan A. Asangani, Robert J. Lonigro, Arul M. Chinnaiyan, Sooryanarayana Varambally. Role of microRNA-34a in regulating oncoprotein STMN1 [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 475. doi:10.1158/1538-7445.AM2017-475
Abstract 4750: Predicting severe hematologic toxicity from extended-field chemoradiation of para-aortic nodal metastases from cervical cancer
Authors: Yan Kevin , Ramirez Ezequiel , Gu Xuejun , Albuquerque Kevin 
Published: July 2017

Abstract
Background and Purpose: To determine significant factors predictive for severe hematologic toxicity (HT) in cervical cancer patients with para-aortic lymph node (PALN) metastasis treated with concurrent chemoradiation with a specific focus on radiation dose to total bone marrow (BMTOT) and active bone marrow (BMACT). To create a nomogram using significant factors to predict HT in these patients.
Material and Methods: 38 Patients with cervical cancer and PALN metastasis who underwent 18F-FDG-PET / CT before treatment with extended field radiation therapy (EFRT) and concurrent cisplatin were analyzed. BMACT was defined as the region within BMTOT with a standardized uptake value (SUV) greater than or equal to the mean for the individual. Blood counts were collected weekly from the beginning of radiation treatment to the end of radiation treatment. HT was graded based on the guidelines set by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0.
Results: 19 patients (50%) had Grade 3 or higher hematologic toxicity (HT3+), not including lymphocyte toxicity. Patients who were obese (n=12) were less likely to get HT3+ compared to patients who were not obese (p=0.03) despite getting the same weight related dose of chemotherapy. Volume of BMTOT receiving 20 Gy, 30 Gy, and 45 Gy were significant predictors for HT3+ at 78.56% (p=0.01), 47.14% (p=0.00), and 20.36% (p=0.01) respectively. Volume of BMACT receiving 10 Gy, 20 Gy, 30 Gy, and 45 Gy were significant predictors for HT3+ at 95.50% (p=0.03), 80.52% (p=0.05), 59.64% (p=0.03), and 31.74% (p=0.01) respectively. Through logistic regression, the probability of developing HT3+ is given by the equation: Prob(HT3+) = 1 / (1 + exp(7.34 + 0.22*BMI - 0.44*Mean Dose to BMTOT)). Patients who had HT3+ received an average of 4 cycles of chemotherapy and 62 days of treatment time, significantly different than the 4.74 chemotherapy cycles and 53 days of treatment in patients without HT3+ (p=0.05, 0.00 respectively).
Conclusions: Both higher patient BMI and bone marrow irradiation were associated with HT3+. A simplified nomogram has been created to predict HT3+ in these patients. Radiation parameters have been identified for cervical cancer patients with PALN involvement receiving EFRT concurrently with chemotherapy. Bone marrow sparing approaches for EFRT need to be addressed to improve patient care.
Citation Format: Kevin Yan, Ezequiel Ramirez, Xuejun Gu, Kevin Albuquerque. Predicting severe hematologic toxicity from extended-field chemoradiation of para-aortic nodal metastases from cervical 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 4750. doi:10.1158/1538-7445.AM2017-4750
Abstract 4753: Prognostic significance of galectin-1 expression in patients with glioblastoma multiforme following radiotherapy
Authors: Huang Eng-Yen , Chou Shang-Yu 
Published: July 2017

Abstract
Purpose: Galectin-1 is a radioresistant marker and prognostic factor in our previous study for cervical cancer. The aim of current study is to determine the prognostic significance of galectin-1 expression level in patients with glioblastoma multiforme (GBM) undergoing adjuvant radiotherapy (RT).
Materials and Methods: We included 45 patients with GBM who treated with maximal safe surgical resection or biopsy only, followed by adjuvant RT of EQD2 &gt;= 60 Gy (equivalent doses as 2-Gy fractions) for homogeneous treatment. Paraffin-embedded tissues acquired from the Department of Pathology were analyzed using immunohistochemistry staining for galectin-1 expression. Overall survival (OS) and cancer-specific survival were compared between strong and weak expression of galectin-1.
Results: According to univariate analysis for optimal cutoff of galectin-1 expression level, better median survival (27.9 months) in patients with weak level than that (10.7 months) in patients with strong level (p = 0.009) was revealed. We compared characteristics between weak and strong galectin-1 expression level, and only galectin-3 expression level was correlated. The weak galectin-1 expression group displayed a 3-year survival rate of 27.3% and 3-year cancer-specific survival (CSS) rate of 27.3%, but which are only 5.9% and 7.6% respectively in strong galectin-1 expression group (p = 0.009 and 0.020, respectively). Cox regression was used to confirm that the role of galectin-1 expression level (weak vs. strong) is a significant factor of OS (p = 0.020) and CSS (p = 0.022). Other parameters such as galectin-3 expression level, ECOG performance, gender, operation method, age &gt; 50 years, or radiation field were not significant factors.
Conclusion: Galectin-1 expression level affects OS and CSS in patient with GBM treated with adjuvant RT.
Citation Format: Eng-Yen Huang, Shang-Yu Chou. Prognostic significance of galectin-1 expression in patients with glioblastoma multiforme following radiotherapy [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 4753. doi:10.1158/1538-7445.AM2017-4753
Abstract 4757: Radioresistance is linked with stem-like properties via activation of aryl hydrocarbon receptor
Authors: Liu SHuang , Yan Bin , Tao Yongguang 
Published: July 2017

Abstract
Most cancer patients receive radiotherapy in the course of their disease and the occurrence of radioresistance is associated with a poor prognosis for cancer patients. The molecular pathways that drive the enhanced tumorigenic potential during the development of radioresistance are poorly understood. Here, we demonstrate that the aryl hydrocarbon receptor (AhR) plays a vital and previously unrecognized role in the maintenance of stem-like cells that are isolated from radioresistant epithelial lung cancer and nasopharyngeal carcinoma. AhR promotes the stem-like phenotype and drives metastasis by directly targeting the promoters of ‘stemness’ genes, such as the ATP-binding cassette sub-family G member 2 (ABCG2) gene. Cancer cell populations enriched for ABCG2 expression (CD338+) show an elevated ‘stemness’ signature and are more prone to cancer progression in vitro and in vivo. Ubiquitin C-terminal hydrolase-L3 (UCHL3), a deubiquitinating enzyme, may counteract AhR, while IKKα, a bone fide chromatin modifier, may directly activate stemness related genes. The radioresistant cancer cell sublines are associated with a hybrid state in epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET), and elevated tumor associated macrophages and proinflammatory factors. Moreover, the radioresistant sublines display high levels of oncometabolites, including α-ketoglutarate, and treatment of cancer cells with α-ketoglutarate enhances their stem-like properties through activation of the AhR. Thus AhR is functionally linked with radioresistance in lung cancer and nasopharyngeal carcinoma, and it drives tumorigenesis by an epithelial and mesenchymal composition, tumor associated macrophages and oncometabolites.
Note: This abstract was not presented at the meeting.
Citation Format: SHuang Liu, Bin Yan, Yongguang Tao. Radioresistance is linked with stem-like properties via activation of aryl hydrocarbon receptor [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 4757. doi:10.1158/1538-7445.AM2017-4757
Abstract 4770: Novel CXCR3 allosteric modulators inhibit breast cancer stem cells and metastasis
Authors: Kundu Namita , Brox Regine , Ma Xinrong , Reader Jocelyn , Tschammer Nuska , Fulton Amy M. 
Published: July 2017

Abstract
There is an urgent need to identify molecular targets that are relevant to metastatic and/or stem-like cancer cells (CSC). Theoretically, surface-expressed G-protein coupled receptors on CSC are attractive therapeutic targets. There is considerable evidence that the inflammatory milieu of the tumor microenvironment drives CSC and we now show that two isoforms of the chemokine receptor CXCR3 play important but distinct roles in cancer behavior. In the bulk tumor cell population, CXCR3, isoform A is highly expressed relative to CXCR3B. CXCR3A is critical to metastatic success. CXCR3, isoform B, is highly upregulated in breast cancer CSC. When CXCR3B is gene-silenced in a model of basal-type, metastatic breast cancer, tumorsphere-forming capacity is reduced and the aldehyde dehydrogenase-positive (ALDH1+) population is correspondingly decreased. Conversely, overexpression of CXCR3B enhances these CSC properties. Thus, CXCR3B is critical to maintenance of the phenotype and function of breast CSC. CXCR3 ligands CXCL9, CXCL10 and CXCL11 all bind with high affinity to CXCR3, however, each ligand is coupled to different intracellular signaling pathways. For example, others have reported that, in HEK cells, CXCL10 strongly induces ERK activation, but CXCL11 does not. In our hands, CXCL11 more potently induces an ALDH1+ population in MDA-MB-231 cells compared to CXCL10. We have developed novel allosteric modulators of CXCR3 that demonstrate probe (ligand)-dependence. BD64 preferentially inhibits CXCL11-mediated β-arrestin 2 recruitment relative to inhibition of GPCR signaling; BD103 is significantly more effective at blocking CXCL11 versus CXCL10-mediated GPCR signaling. Neither BD64 nor BD103 affects the proliferation of non-CSC, however both compounds inhibit the ability of CSC to form tumorspheres. Furthermore, both CXCR3 antagonists reverse ligand-mediated induction of the ALDH1+ fraction. Most interesting is that both BD64 and BD103 effectively inhibit tumor cell colonization of the lung. These data suggest that optimal tumor control will be achieved when both metastatic, CXCR3Ahigh as well as CXCR3Bhigh CSC populations are inhibited by highly specific CXCR3 modulators.
Note: This abstract was not presented at the meeting.
Citation Format: Namita Kundu, Regine Brox, Xinrong Ma, Jocelyn Reader, Nuska Tschammer, Amy M. Fulton. Novel CXCR3 allosteric modulators inhibit breast cancer stem cells and metastasis [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 4770. doi:10.1158/1538-7445.AM2017-4770
Abstract 4771: The role of Hes1 in the normal and tumor stem cells of the intestine
Authors: Goto Norihiro , Fukuda Akihisa , Chiba Tsutomu , Seno Hiroshi 
Published: July 2017

Abstract
Notch-Hes pathway plays a crucial role in the differentiation, proliferation, and tumorigenesis of the intestine. We previously reported that prenatal deletion of Hes1 reduces intestinal tumor proliferation; however, postnatal deletion of Hes1, which recapitulates Hes1-targeted tumor therapy, has not been thoroughly investigated. Here, we elucidated the novel role of Hes1 in normal stem cells (NSCs) and tumor stem cells (TSCs) of the adult intestine. First, we deleted Hes1 in Lgr5-expressing or Bmi1-expressing NSCs and performed lineage tracing using Lgr5CreERT2/+; Hes1flox/flox; Rosa26LacZ/+ and Bmi1CreER/+; Hes1flox/flox; Rosa26LacZ/+ mice. After Hes1 deletion, Lgr5-expressing or Bmi1-expressing NSCs gave rise to progeny cells, but could not self-renew. However, Hes1 deletion in NSCs did not disrupt intestinal homeostasis, because Hes1-positive NSCs were newly generated soon after Hes1-deleted NSCs were depleted. Next, we stabilized beta-catenin for intestinal tumor formation and deleted Hes1 in Lgr5-expressing cells using Lgr5CreERT2/+; Ctnnb1lox(ex3)/+; Hes1flox/flox mice. Tumor formation was dramatically suppressed, and the animal survival was significantly improved, suggesting that Hes1 is required for the initiation of intestinal tumor formation. Finally, we deleted Hes1 in Lgr5-expressing TSCs of established intestinal tumors using Lgr5CreERT2/+; Hes1flox/flox; ApcMin/+ mice. Of note, Hes1 deletion in TSCs of established intestinal tumors induced immediate apoptosis of TSCs and significantly reduced the number of tumors. qRT-PCR analysis of sorted Lgr5-expressing cells one day after Hes1 deletion revealed upregulation of pro-apoptotic genes and downregulation of anti-apoptotic genes in Hes1-deleted TSCs, but not in Hes1-deleted NSCs. We also deleted Hes1 in Dclk1-expressing TSCs of established intestinal tumors, and confirmed that, irrespective of stem cell markers analyzed, Hes1 deletion in TSCs leads to tumor regression by inducing immediate apoptosis in TSCs. Taken together, Hes1 is required in different ways for the maintenance of NSCs and TSCs: Hes1 deletion in NSCs does not perturb homeostasis, whereas Hes1 deletion in TSCs leads to tumor regression. Furthermore, Hes1 is necessary for the initiation of intestinal tumor formation. Therefore, we propose Hes1 is a novel tumor-specific therapeutic target.
Citation Format: Norihiro Goto, Akihisa Fukuda, Tsutomu Chiba, Hiroshi Seno. The role of Hes1 in the normal and tumor stem cells of the intestine [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 4771. doi:10.1158/1538-7445.AM2017-4771