bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 656: PD-L1 expression in primary lesions vs metastatic sites and by demographics in advanced urothelial carcinoma samples
Authors: Zajac M , Boothman A M. , Ben Y , Gupta A , Jin X , Antal J , Sharpe A , Scott M , Rebelatto M , Walker J 
Published: July 2017

Abstract
Background: Determination of programmed cell death ligand-1 (PD-L1) expression levels in tumors may help physicians understand which patients (pts) are most likely to respond to anti-PD-1/PD-L1 therapies in urothelial carcinoma (UC). Understanding the impact of different sample types and demographics on PD-L1 expression is important to determine suitability of tumor biopsies for testing.
Methods: As of July 24, 2016, 363 pts screened in the UC cohort of Study CD-ON-MEDI4736-1108 (NCT01693562) had tissue available for analysis and 47 pts had provided paired primary and metastatic samples. FFPE samples were tested in a central laboratory with the VENTANA PD-L1 (SP263) Assay using a BenchMark ULTRA instrument. Pts were classified as having either PD-L1 high (PD-L1 expression ≥25% either on tumour cells [TC] or immune cells [IC]) or PD-L1 low/negative (&lt;25% on TC and IC) tumors. PD-L1 high prevalence was reported in primary vs metastatic sites, and by age, sex and race.
Results: PD-L1 status was evaluable for 332/363 (91.5%) pts (175/332 [52.7%] PD-L1 high and 157/332 [47.3%] PD-L1 low/negative) whose UC specimens were tested (intent to diagnose [ITD] population). Overall percentage agreement between paired primary and metastatic samples, based on combined TC/IC scoring ≥25%, was 74.5% (95% CI 59.7 - 86.1%). In the ITD population, using only the samples from which patient PD-L1 expression status was determined, PD-L1 high prevalence in primary and metastatic samples was 57.1% and 50.9% respectively (p=0.343, not significant). The proportion of pts with PD-L1 high status was not enriched in any demographic group (Table).
Conclusions: Initial data from UC pts in Study 1108 showed similar PD-L1 high prevalence in primary and metastatic lesions and good concordance between paired primary and metastatic samples. These results build optimism that samples obtained from either location could be used to determine PD-L1 status. Further data are needed to confirm these findings.
Patients screened for UC cohort with evaluable PD-L1 result - ITD population (n = 332)ParameterPD-L1 high, n (%)P valueAge, years&lt;65 (n=131)73 (55.7%)0.438≥65 (n=201)102 (50.8%)SexMale (n=236)127 (53.8%)0.610Female (n=96)48 (50.0%)RaceAsian (n=52)23 (44.2%)Asian vs White: 0.406Black or African American (n=10)6 (60.0%)White (n=218)113 (51.8%)Other (n=9)4 (44.4%)
Citation Format: M Zajac, A M. Boothman, Y Ben, A Gupta, X Jin, J Antal, A Sharpe, M Scott, M Rebelatto, J Walker. PD-L1 expression in primary lesions vs metastatic sites and by demographics in advanced urothelial carcinoma samples [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 656. doi:10.1158/1538-7445.AM2017-656
Abstract 666: CD37 tetraspanin as a novel biomarker for PD-1 blockade in diffuse large B-cell lymphoma
Authors: Xu-Monette Zijun Y. , Young Ken H. 
Published: July 2017

Abstract
PD-1 immune checkpoint blockade reconstituting antitumor immunity has changed the cancer treatment paradigm. PD-1 blockade has been successful in many types of solid tumors and Hodgkin lymphoma, but not yet for diffuse large B cell lymphoma (DLBCL), the most common aggressive B-cell lymphoma. We found several biomarkers including loss of CD37 tetraspanin expression in DLBCL correlated with increased PD-1 expression suggesting potential sensitivity of these DLBCL subsets to PD-1 blockade. CD37 (TSPAN26) is a member of the tetraspanin superfamily, widely expressed on normal and malignant mature B-cells and downregulated in plasma cells. It has been documented that CD37 plays important roles in T-cell-B-cell interactions, B-cell humoral response triggered by B-cell receptor cross-linking, and a balance between immune responses and tolerance. Interestingly, in a large cohort of DLBCL patients, we found that loss of CD37 expression in DLBCL predicts strikingly decreased overall and progression-free survival rates, and that PDCD1 gene expression was upregulated in CD37-negative activated B-cell-like (ABC) DLBCL by gene expression profiling, whereas the costimulatory molecule ICOSLG was upregulated in CD37+ germinal center B-cell-like (GCB) DLBCL. Using the new fluorescent multiplex technology, we further measured PD-1 and PD-L1 expression at the protein level on lymphoma cells and immune cells in the tumor microenvironment, and found that PD-1 protein levels were increased on both cytotoxic and helper T-cells infiltrating in CD37-negative DLBCL either of GCB or ABC subtype. These novel discoveries suggest that CD37 is important for sustained antitumor adaptive immunity, that immune dysregulation plays an important role for poor clinical outcomes in DLBCL, and that CD37-negative DLBCL may be sensitive to PD-1 blockade. In summary, loss of a CD37 tetraspanin was found to correlate with PD-1 overexpression in DLBCL clinical samples, and CD37 may serve as a novel biomarker for anti-PD-1 immunotherapy clinical trials in DLBCL.
Note: This abstract was not presented at the meeting.
Citation Format: Zijun Y. Xu-Monette, Ken H. Young. CD37 tetraspanin as a novel biomarker for PD-1 blockade in diffuse large B-cell lymphoma [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 666. doi:10.1158/1538-7445.AM2017-666
Abstract 680: Prognostic impact of OPN and DKK1 in patient of hepatocellular carcinoma after hepatectomy
Authors: Seo YunSung , Byeon Hye Rim , Park In Hae , Lee Seung Duk 
Published: July 2017

Abstract
The new biomarkers are essential for improving the survival and prognosis of hepatocellular carcinoma(HCC) patients. Alpha-fetoprotein(AFP) is the most widely used biomarker. But the low sensitivity and specificity limits its clinical application. Recent study validated the diagnostic capability of osteopontin(OPN) and dickkopf-1(DKK1) and assessed the combination of AFP, DKK1, and OPN as a panel for the diagnosis of HCC. Based on these previous studies, we hypothesized that combination of OPN and DKK1 can be used to as a marker for prognosis to patient of HCC after hepatectomy. From January 2006 to December 2008, patients undergoing hepatectomy for hepatocellular carcinoma were screened serum that has been stored in the Bank of tumor. To target the selected patient, it was confirmed that the remaining tissue specimen is stored after diagnosis. Serum of the patients was used to investigate the OPN and DKK1 by ELISA. In the paraffin block were prepared unstained slide and OPN and DKK1 level checked by IHC. It examined the correlation between prognosis and biomarkers through statistical analysis. AFP, OPN(serum level) and DKK1(serum level) are an independent prognostic factor for overall survival(OS) in HCC after hepatectomy(n=60, P=0.0204, 0.0167 and 0.0455 respectively). New biomarkers combinations based on the AFP existing biomarker are showed a falling curve of the overall survival(OS) and disease-free survival(DFS) in Kaplan Meier curve. In conclusion, combination of OPN, DKK1 and AFP as a biomarker could support the correct diagnosis for HCC after hepatectomy.
Note: This abstract was not presented at the meeting.
Citation Format: YunSung Seo, Hye Rim Byeon, In Hae Park, Seung Duk Lee. Prognostic impact of OPN and DKK1 in patient of hepatocellular carcinoma after hepatectomy [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 680. doi:10.1158/1538-7445.AM2017-680
Abstract 686: onTARGET: a new computational strategy to predict in vivo relevant targets against neuroblastoma
Authors: Almstedt Elin , Lönnstedt Ingrid , Krona Cecilia , Nelander Sven 
Published: July 2017

Abstract
One of the main bottlenecks of anticancer drug development is the assessment of the in vivo relevance of emerging therapies. Previously, drugs that suppress the in vivo progression of neuroblastoma have been hard to identify. To address this problem, we propose a new computational technique, onTARGET, that enables researchers to select, with good accuracy, compounds that are likely to induce changes in cellular pathways that are consistent with specific clinical outcomes and subgroups.
onTARGET prediction is based on an integration of massive expression and other data resources, including the NIH LINCS dataset (with 1,300,000 expression profiles), the NIH TARGET and R2-AMC neuroblastoma cohorts, and our own in-house databases. In a first step, the datasets are preprocessed by factor analysis to remove systematic bias in these large data sets. In a second step, Bayesian statistics are applied to prioritize compounds whose cellular responses match clinically relevant differences between patient subsets, such as MYCN status, survival hazard ratio, or histopathological assessment.
To evaluate the method, we used onTARGET prediction to identify compounds and gene targets relevant for clinical outcomes in the NIH-TARGET (n=249) and R2-AMC (n=98) neuroblastoma cohorts. The algorithm confirmed existing targets and made interesting predictions. Of 50 the top-ranking compounds associated with a survival outcome, agents targeting the mTOR/PI3K axis are highly prevalent. The algorithm correctly predicts targeting of the MYC pathway, and predicts possible modulators of MYC signaling, such as TRRAP, AURKA and BMP2. In addition to nominating agents with a favorable outcome, the algorithm can also flag compounds that might worsen prognosis, further facilitating the prioritization of targets for evaluation.
In summary, onTARGET may guide target selection for neuroblastoma studies and can be adapted for other cancers as well. The many targets that were identified immediately suggest an opportunity for continued evaluation in cells and in vivo models. This work has been initiated in collaboration with researchers at Lund University.
Citation Format: Elin Almstedt, Ingrid Lönnstedt, Cecilia Krona, Sven Nelander. onTARGET: a new computational strategy to predict in vivo relevant targets against neuroblastoma [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 686. doi:10.1158/1538-7445.AM2017-686
Abstract 70: Elucidating the roles of antibody pharmacokinetics and maleimide stability in the toxicology of antibody-drug conjugates
Authors: Neff-LaFord Haley , Zapata Franciso , Schultz Wendi , Balasubramanian Cindy , Pittmen Paul , Hengel Shawna , Sanderson Russell , Chemuturi Nagendra , Setter Jocelyn , Lyon Robert P. 
Published: July 2017

Abstract
Antibody-drug conjugates (ADCs) continue to emerge as effective therapeutics in a variety of oncology indications, with two agents currently approved and many more in late-stage clinical trials. These ADCs employ drug-linkers that were developed many years ago, and are now recognized to have properties that may adversely impact the activity and toxicology of the ADCs prepared with them. Two such properties that are now well appreciated are the reversibility of maleimide-based drug conjugation, and the impact of drug conjugation on the pharmacokinetics of the ADC. We recently reported advances in drug-linker design that independently address both of these properties, resulting in the irreversible conjugation of drugs which have minimal impact on antibody pharmacokinetics, even at high levels of drug loading (Nature Biotechnology 32, 1059-1062 (2014), Nature Biotechnology 33, 733-735 (2015)). We have now prepared drug-linkers of monomethylauristatin E (MMAE) that orthogonally employ these features to enable a systematic evaluation of the relative contributions of maleimide instability and accelerated plasma clearance on the in vivo behavior of MMAE ADCs. Biodistribution studies with these molecules have revealed that the concentration of released MMAE in normal tissues is greatly impacted by the rate of ADC clearance (fast clearance results in greater Cmax of free drug), while stabilization of the maleimide has a relatively small effect. These differences in observed free drug concentrations were paralleled in tolerability studies, with ADC clearance rates exerting a greater impact on hematology parameters than maleimide stability. Collectively, these results suggest that ADC pharmacokinetics dominate the biodistribution and toxicology profiles for a given drug payload, with conjugate stability playing a relatively minor role.
Citation Format: Haley Neff-LaFord, Franciso Zapata, Wendi Schultz, Cindy Balasubramanian, Paul Pittmen, Shawna Hengel, Russell Sanderson, Nagendra Chemuturi, Jocelyn Setter, Robert P. Lyon. Elucidating the roles of antibody pharmacokinetics and maleimide stability in the toxicology of antibody-drug conjugates [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 70. doi:10.1158/1538-7445.AM2017-70
Abstract 710: Identification of autoantibody to ECH1 & HNRNPA2B1 as potential biomarkers in the early detection of lung cancer
Authors: Dai Liping , Li Jitian , Tsay Jun-Chieh J. , Wang Xiao , Munger John S. , Pass Harvey , Rom William N. , Tan Eng M. , Zhang Jian-Ying 
Published: July 2017

Abstract
Background: Identification of biomarkers for early detection of lung cancer (LC) may lead to more effective treatment and reduction of mortality.
Methods: Serological proteome analysis (SERPA) was used to identify proteins around 34 kDa, which had been previously recognized by autoantibody in sera from LC patients. We have validated autoantibody response in sera from 90 LC patients, 89 normal controls by using immunoassay. Another independent cohort of 25 LC patients with 219 serial serum samples and 56 matched normal controls were examined to evaluate whether the autoantibody can be detected in the preclinical stage.
Results: The proteins with molecular weight of 34 kDa were identified as ECH1, GAPDH and HNRNPA2B1. In the validation study, autoantibody to ECH1 achieved an area under the curve (AUC) of 0.799 with sensitivity of 62.2% and specificity of 95.5% in discriminating LC from normal individuals, and showed negative correlation with tumor size (rs=0.-256, p=0.023). Autoantibody to HNRNPA2B1 performed an AUC of 0.874 with sensitivity of 72.2% and specificity of 95.5%, and showed negative correlation with lymph node metastasis (rs=0.-279, P=0.012). By using longitudinal preclinical samples, autoantibody to ECH1 showed an AUC of 0.763 with sensitivity of 60.0% and specificity of 89.3% in distinguishing LC with matched normal controls, and elevated autoantibody levels could be detected greater than two years prior to LC diagnosis.
Conclusions: ECH1 and HNRNPA2B1 are autoantigens that elicit autoimmune responses in LC and can be used as potential biomarkers for the early detection of LC.
Funding support: This work was supported by the National Natural Science Foundation of China (81672917, 81372371) and the National Institutes of Health (SC1CA166016 and U01CA086137).
Citation Format: Liping Dai, Jitian Li, Jun-Chieh J. Tsay, Xiao Wang, John S. Munger, Harvey Pass, William N. Rom, Eng M. Tan, Jian-Ying Zhang. Identification of autoantibody to ECH1 & HNRNPA2B1 as potential biomarkers in the early detection of lung 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 710. doi:10.1158/1538-7445.AM2017-710
Abstract 722: Circulating EBV microRNA BART2-5p helps to diagnose nasopharyngeal carcinoma &lt screen for high risk individuals precisely
Authors: Jiang Chen , Li Lei , Jiangchao Li , Xie Shang-hang , Cao Su-mei , Guan Xin-yuan 
Published: July 2017

Abstract
Nasopharyngeal carcinoma is an EB-virus associated malignancy which is highly prevalent in Southeast Asia. If diagnosed early, the 5 year disease-free survival rate is about 90%. However, most patients have already developed local or regional invasion when diagnosed, which results in poor prognosis. So it is essential to develop biomarkers to screen high risk individuals or diagnose the disease at early stages. As nasopharyngeal carcinoma is closely related to EBV infection and microRNAs encoded by BART region (BamHI A Rightward Transcripts) is abundant in NPC, we propose to identify biomarkers from those BART microRNAs. To quantify the copy number of microRNAs in serum samples, we used Taqman Probe-based qPCR. After adding Spiked-in Control (Mixture of Cel-39,Cel-54, Cel-238) to each 100ul serum sample, we extracted total RNA and reverse transcribed microRNA into cDNA with corresponding Taqman primers. Meanwhile, microRNA mimics with known copy number were serial diluted and reverse transcribed along with the samples. qPCR was performed to quantify the level of microRNAs in these samples with diluted cDNA and Taqman Probe. All data was normalized by Spiked-in controls and exact copy number of each microRNA was calculated through the standard curve generated by the serial diluted microRNA mimics. Here, we screened 17 BART microRNAs in discovery stage and found BART 2-5p as a candidate biomarker. In training cohort consisting of 266 patients with nasopharyngeal carcinoma and controls from Hong Kong, the sensitivity, specificity and AUC is 93.2%, 89.8%,0.976 respectively. The results are similar in validation cohort 1 constituted by 376 patients and controls from Guang Zhou. To evaluate the ability of BART 2-5p to distinguish preclinical NPC patients from healthy high risk individuals, we established a nested case-control study with serum samples prospectively collected from 10 NPC patients at least one year prior to their clinical diagnosis and 92 matched healthy high risk controls from a screening scheme conducted in South China. The sensitivity and specificity is 90.0% and 31.5%. Taken together, EBV microRNA BART2-5p is a promising biomarker to improve NPC diagnosis and target preclinical patients more precisely than serologic test.
Citation Format: Chen Jiang, Lei Li, Li Jiangchao, Shang-hang Xie, Su-mei Cao, Xin-yuan Guan. Circulating EBV microRNA BART2-5p helps to diagnose nasopharyngeal carcinoma &lt screen for high risk individuals precisely [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 722. doi:10.1158/1538-7445.AM2017-722
Abstract 728: Development and validation of ColoScape™ - a new colorectal cancer mutation detection assay
Authors: Powell Michael J. , Peletskaya Elena , Vallerga Anne , Sun Qing , Pastor Larry , Zhang Aiguo 
Published: July 2017

Abstract
Introduction: Colorectal cancer is a highly preventable disease as early detection increases rates of patient survival to near 100%. Herein we report the development and validation of a novel multigene mutation biomarker real-time PCR based assay for qualitative detection of colorectal cancer associated biomarkers that comprise tumor specific mutations in the following genes: APC (Exon 15), KRAS (Exon 2), BRAF (Exon 15) and CTNNB1 (Exon 3) called ColoScapeTM . The assay allows the sensitive detection of the presence or absence of mutations in the targeted regions of the genes interrogated.
Methodology: The high sensitivity of this multigene biomarker assay is achieved due to xenonucleic acid (XNA) probe technology. XNA probes are novel backbone modified oligomers having natural nucleoside bases (A,T,C and G) that hybridize by Watson-Crick base pairing to natural DNA and RNA with much higher binding affinity than natural deoxyribonucleic acid oligomers of the same sequence. XNA probes are designed that bind to the selected wild-type sequences at the respective genetic loci in the target genes. These XNA probes have a much higher Tm than the primer annealing temperature and suppress amplification of WT DNA templates and only allow amplification of the target mutant DNA templates in the sample. Both single nucleotide polymorphisms (SNP’s) and insertion/deletions (indels) mutations can be detected. For each of the selected mutation sites primers and FAM-labeled TaqMan hydrolysis probes were designed and tested together with the selected XNA oligomers and analytical assay performance confirmed. An internal PCR control amplicon selected in the Human β-Actin (ACTB) gene was employed utilizing a HEX-labeled TaqMan probe. Performance parameters of the assay were established on DNA of colorectal cancer patients extracted from FFPE as well as reference DNA materials (synthetic and cell line derived DNA). The assay demonstrates high sensitivity and specificity in detection of colon cancer and adenoma samples based on the set of biomarkers involved in colorectal cancer neogenesis and disease progression.
Conclusion: The ColoScapeTM Colorectal Cancer Mutation Detection assay is shown to be a sensitive tool intended to facilitate research in colon cancer development, early detection, disease monitoring and therapeutic interventions.
Citation Format: Michael J. Powell, Elena Peletskaya, Anne Vallerga, Qing Sun, Larry Pastor, Aiguo Zhang. Development and validation of ColoScape™ - a new colorectal cancer mutation detection assay [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 728. doi:10.1158/1538-7445.AM2017-728