bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 6436: A potential treatment for malignant glioblastoma: Silver nanoparticles and low-level laser combination
Authors: Atluri Rohini , Korir Daniel , Tyagi Nishant , Kim Eunyoung , Choi Tae-Youl , Simmons Denise P. 
Published: September 2020

Abstract
Glioblastomamultiforme (GBM) is a dreadful primary brain tumor characterized with extremely poor prognosis and survival rate, despite available treatments. The failure of current therapies to eliminate specific subpopulations within heterogeneous GBM has been considered a key factor contributing to the inevitable recurrence after treatments. To address this concern, it is necessary to develop novel treatments, which can kill all the GBM cells or at least convert the heterogeneous GBM population to homogeneous populations, which can be easily targeted. In this study, we investigated the effects of Ag-PMMA-PAA nanoparticles (Silver np's) on human malignant glioma(U251) cells and Silver np's role in combinational use with low-level He-Ne laser (632.8nm) against U251 cells.The Silver np's were synthesized using a green chemistry approach and were then characterized using spectroscopic methods. Dose and time dependent studies revealed that the maximum killing (81%) of U251 cells occurred at 225μM Silver np's over 6 hours. Moreover, combined HeNe laser exposure resulted in overall cell death of 92%. Western analysis suggests caspase family members, other than caspase 9, are involved in killing Silver np treated U251 cells or the combination treatment. Thus, our Silver np and low-level laser combination treatment could have a potential application in enhancing chemotherapy for malignant glioma.
Citation Format: Rohini Atluri, Daniel Korir, Nishant Tyagi, Eunyoung Kim, Tae-Youl Choi, Denise P. Simmons. A potential treatment for malignant glioblastoma: Silver nanoparticles and low-level laser combination [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6436.
Abstract 6442: Investigation of custom biomarkers on circulating tumor cells from clinical samples using RarePlex® Developer Kits
Authors: Lo Edward , Campton Daniel , Ramirez Arturo , Costandy Lillian , Gardner Brady , Houston Ryan , Itamoto Heather , Werbin Jeffery L. , Gadi VK , Mojica Tanisha , Clein Alisa , Higano Celestia , Sabath Daniel E. , Kaldjian Eric P. , George Tad 
Published: September 2020

Abstract
Enumeration and phenotypic profiling of circulating tumor cells (CTCs) can give important information about tumor progression, presence of therapeutic targets, and metastatic potential. New and informative cancer-specific biomarkers are being discovered at a rapid pace, so there is a strong need for tools that enable investigator driven assays to best study and utilize these biomarkers. Through the RareCyte platform, we provide sensitive and specific assays that are optimized and validated for CTC enumeration and biomarker expression. RarePlex Developer Kits enable the addition of user-selected antibodies against biomarkers of interest to a CTC detection assay. Here we demonstrate the application of RarePlex Developer Kits to study the presence of a variety of cancer related biomarkers. Using the Developer strategy, we present results for several biomarkers, including HER2, ER, PR, EGFR, Ki67, AR, ARv7, PDL1, and PSMA. We also characterized clinical samples from prostate (AR and ARv7) and breast (HER2 and ER) cancer patients. The biomarkers demonstrated proper localization on or within model CTC control cells when using default antigen retrieval and fixation conditions. For each biomarker, fluorescence intensity cut-offs that segregated negative and positive cell lines were statistically defined to maximize classification accuracy. For clinical samples, breast and prostate cancer sample staining showed expected localization based on available clinical information. In conclusion, RarePlex Developer Kits provide a flexible tool for custom CTC assay development that enables researchers to develop assays in their own lab for characterization of phenotypic heterogeneity.
Citation Format: Edward Lo, Daniel Campton, Arturo Ramirez, Lillian Costandy, Brady Gardner, Ryan Houston, Heather Itamoto, Jeffery L. Werbin, VK Gadi, Tanisha Mojica, Alisa Clein, Celestia Higano, Daniel E. Sabath, Eric P. Kaldjian, Tad George. Investigation of custom biomarkers on circulating tumor cells from clinical samples using RarePlex® Developer Kits [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6442.
Abstract 6450: Circulating hepsin as a novel serum biomarker in prostate cancer patients
Authors: Beard John , Eddington Sam , Bowman Noah , Cole Adam , O'Brien Timothy , Johnson Blake P. 
Published: September 2020

Abstract
Hepsin, a type II transmembrane serine protease, is commonly overexpressed in a variety of epithelial cancers, where its overexpression and concurrent proteolytic activity correlate with tumor progression. Recent studies indicate that Hepsin undergoes activation via autocatalysis and subsequent ectodomain shedding, thus highlighting its potential as a serum-based biomarker. Using transgenic mouse models of prostate adenocarcinoma, Hepsin overexpression has previously been implicated in disease progression and, notably, metastases that are neuroendocrine in nature. Collectively, these findings led us to explore the potential diagnostic utility of Hepsin expression in prostate cancer progression, inclusive of metastatic variants. Here, we reanalyzed pre-existing, publicly available gene expression datasets (2 datasets, 326 patient samples), which revealed a significant upregulation of Hepsin gene expression in tumor tissue versus benign tissue and further pronounced upregulation in androgen-dependent and -independent metastatic lesions. To further examine the potential correlation of Hepsin overexpression to androgen-independence, we reanalyzed in vitro data comparing LNCaP parental versus androgen-independent LNCaP subclones. This analysis revealed a stepwise increase in Hepsin expression over the course of androgen deprivation, which was accompanied by a concomitant decrease in PSA expression. Lastly, to evaluate circulating hepsin protein levels as they occur in patient serum, a total of 424 subjects suspected of prostate cancer were analyzed for circulating Hepsin levels from 2015 to 2018 at the time of biopsy and followed for recurrence or survival until the end of the study. Serum Hepsin levels, as determined by enzyme-linked immunosorbent assay, rendered a specificity of 89% (Gleason &lt; 6 (3+3); Hepsin positive, &gt;100 ng/mL). Within this cohort, 18 patients presented with biochemical recurrence, of which 44% were Hepsin positive and exhibited a 22-month accelerated clinical path to recurrence versus Hepsin negative patients. Collectively, these results highlight the longitudinal diagnostic potential of circulating Hepsin levels in the prostate cancer setting.
Citation Format: John Beard, Sam Eddington, Noah Bowman, Adam Cole, Timothy O'Brien, Blake P. Johnson. Circulating hepsin as a novel serum biomarker in prostate cancer patients [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6450.
Abstract 6468: Prognostic genomic alterations associated with recurrence after primary therapy for patients with luminal B breast cancer
Authors: Liu Chun-Yu , Chen Ji-Lin , Yang Yi-Ting , Tsai Yi-Fang , Chao Ta-Chung , Tan Kien Thiam , Wang Wan-Lun , Lien Pei-Ju , Chen Shu-Jen , Tseng Ling-Ming 
Published: September 2020

Abstract
Purpose: Luminal type breast cancers account for the most common subtypes of breast cancers, among which luminal B subtype is relatively faster tumor growing and confers substantial risk of recurrence after primary treatment despite adjuvant endocrine therapy. Understanding the molecular alterations underlying the poorer survival outcome for luminal B tumors represents an unmet medical need.
Experimental design: The archival samples of 16 recurrences within 5 years, 3 recurrences between 5-10 years and 24 non-recurrence tumor tissues from luminal B breast cancer patients were retrieved. Genomic alterations of these 43 breast cancer samples were detected using deep next-generation sequencing of a 440-gene panel. The mRNA levels of candidate genes in breast cancer patients were analyzed from The Cancer Genome Atlas (TCGA) database.
Results: Overall, genomic alterations were found in 340 genes, including single nucleotide variants and copy number variation. Comparing to the non-recurrence tumors, NUP98 (31.3%), MAPK4 (18.8%), PTEN (18.8%), PER1 (18.8%) and TRIP11 (18.8%) showed higher population frequency in the recurrence tumors, and IGF2R (50.0%), PIM1 (45.8%) and ROS1 (37.5%) were dominate in the non-recurrence tumors. After a validation with the public clinical dataset, we identified three potential prognostic biomarkers, including NUP98, PER1, and TRIP11. We observed missense mutation or copy number deletion of NUP98, PER1 and TRIP11 in early recurrence tumors. Data from TCGA database exhibited patients with breast cancer harbored lower NUP98, PER1 and TRIP11 transcripts levels. Notably, lower NUP98, PER1 and TRIP11 expression levels correlated with worse recurrence-free survival in luminal B breast cancer. Interestingly, based on algorithm for visualization of protein interaction network, we found these 3 genes were all involved in androgen receptor signaling network.
Conclusion: Our study identified NUP98, PER1, and TRIP11 which potentially served as biomarkers to predict recurrence in luminal B breast cancer. Further research is required to understand the association between genomic alterations and androgen receptor signaling as well as its clinical impact.
Citation Format: Chun-Yu Liu, Ji-Lin Chen, Yi-Ting Yang, Yi-Fang Tsai, Ta-Chung Chao, Kien Thiam Tan, Wan-Lun Wang, Pei-Ju Lien, Shu-Jen Chen, Ling-Ming Tseng. Prognostic genomic alterations associated with recurrence after primary therapy for patients with luminal B breast cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6468.
Abstract 6473: Outcomes of advanced renal cell carcinoma with sarcomatoid features post-cytoreductive nephrectomy in clear cell and non-clear cell disease
Authors: Adashek Jacob J. , Bilotta Alyssa , Chahoud Jad , Li Jiannong , Spiess Philippe E. 
Published: September 2020

Abstract
Background: Cytoreductive nephrectomy in the setting of treatment of advanced renal cell carcinoma with sarcomatoid features (sRCC) has been highly contested in terms of added benefit for survival. Patients with sRCC are known to have a poor prognosis and more aggressive tumor biology.
Methods: Pts with clear cell RCC and non-clear cell RCC underwent cytoreductive nephrectomy in efforts to improve overall survival. Patients were stratified by presence or absence of histologic presence of sarcomatoid features within the tumor samples.
Results: Of 167 patients who underwent cytoreductive nephrectomy, 127 had clear cell, of which 14 had sarcomatoid features and 40 had non-clear cell RCC of which 13 had sarcomatoid features. Median age in the cohort was 62 (range, 56.5-69). The cohort included 119 male (71.3%) and 48 (28.7%) female patients. There were 121 patients with &gt;T3 disease, 24 (14.4%) with T2a/b disease, and 22 (13.2%) with T1a/b disease. In all patients with advanced RCC having sRCC had a significant impact on survival post-cytoreductive nephrectomy (30 vs. 8 mos; HR 2.88; p &lt;0.0001). Additionally, good-risk patients had significantly longer OS compared to intermediate- or poor-risk patients (56 vs 30 vs 10 mos; HR 0.21; p = 0.00016). For patients with clear cell RCC, having sRCC present conferred a poorer significant survival (30 vs 9 mos; HR 2.82; p = 0.0035). Patients with non-clear cell sRCC also had significantly worse outcomes compared to those without sarcomatoid features (30 vs 6.5 mos; HR 3; p = 0.009). When sRCC patients were stratified by whether there was &gt;10% or ≤10% present within the sample, there was no significant difference in overall survival (8 vs 8.5; p = 0.32).
Conclusions: Sarcomatoid features within tumor histology confers significantly poor prognosis. Patients with sRCC regardless of clear cell vs non-clear cell histology have significantly shorter overall survival. Even among patients with 10% or less sarcomatoid features there was no overall survival benefit to cytoreductive nephrectomy. Based on our findings, there appears to be a limited to no role of cytoreductive nephrectomy, if sRCC is identified on pre-treatment biopsy.
Citation Format: Jacob J. Adashek, Alyssa Bilotta, Jad Chahoud, Jiannong Li, Philippe E. Spiess. Outcomes of advanced renal cell carcinoma with sarcomatoid features post-cytoreductive nephrectomy in clear cell and non-clear cell disease [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6473.
Abstract 6483: Performance characteristics of the first FDA-cleared droplet digital PCR (ddPCR) IVD assay for monitoring chronic myelogenous leukemia
Authors: Shelton Dawne N. , Bhagavatula Prasanthi , Sepulveda Nathan , Beppu Lan , Radich Jerald 
Published: September 2020

Abstract
Introduction: Chronic myelogenous leukemia (CML) is a cancer of myeloid cells that accounts for 15-20% of all cases of leukemia. Most CML cases are caused by a translocation between chromosomes 9 and 22 which creates an abnormal fusion gene, BCR-ABL1. The BCR-ABL1 gene expresses an abnormal tyrosine kinase protein that causes unregulated growth and survival of granulocytes. CML is treated with TKIs (tyrosine kinase inhibitors). The concentration of BCR-ABL1 transcript RNA is a marker of disease progression and the effectiveness of TKI treatment.Bio-Rad's QXDx BCR-ABL %IS Kit is an in vitro diagnostic test for the quantification of BCR-ABL transcripts in total RNA from whole blood from individuals diagnosed with Chronic Myeloid Leukemia expressing BCR-ABL1 Fusion transcript types e13a2 and/or e14a2.
Materials and Methods: The QXDx BCR-ABL %IS Kit is a newly launched FDA-approved ddPCR assay from Bio-Rad Laboratories. Reproducibility of results across multiple sites, days, instruments, and users was evaluated using contrived samples consisting of BCR-ABL positive patient samples mixed with negative patient samples. Clinical performance of the kit was evaluated on patient samples, and compared to an already existing FDA-approved test. Clinical performance was further tested in the College of American Pathologists challenge.
Results: The reproducibility study noted negligible contributions to variance from site, instrument, day, and user for samples spanning from MR 0.7-4.2. The mean between the QXDx™ BCR-ABL %IS Kit and the comparator test using a Bland-Altman analysis was 0.16 MR units. The limits of agreement between the two methods indicate that the difference between the two methods should be between 0.47 and -0.14 MR on 95% of tested samples. The QXDx™ BCR-ABL %IS assay demonstrated excellent correlation with the comparator test using a Weighted Deming regression with a Pearson R correlation coefficient of 0.99, slope 1.037 and intercept of 0.1084. College of American Pathologists(CAP) challenges (n=6) were conducted from 2016-2019, QXDx™ BCR-ABL %IS system results were regressed vs the mean values published by CAP yielded a slope of 1 and R2=0.99.
Conclusions: The QXDx™ BCR-ABL %IS Kit on the QXDx™ AutoDG™ Droplet Digital PCR System can be used safely and effectively in the laboratory on t(9;22) positive CML patients for monitoring of treatment with Tyrosine Kinase Inhibitors (TKIs).
Citation Format: Dawne N. Shelton, Prasanthi Bhagavatula, Nathan Sepulveda, Lan Beppu, Jerald Radich. Performance characteristics of the first FDA-cleared droplet digital PCR (ddPCR) IVD assay for monitoring chronic myelogenous leukemia [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6483.
Abstract 6491: Prognostic potential of carcinoembryonic antigen expression patterns in lung adenocarcinoma
Authors: Zheng Ming-Yi , Kuo Yen-Shou , Chou Yu-Ting 
Published: September 2020

Abstract
Carcinoembryonic antigen (CEA) is one of the most commonly used tumor markers. Although the suitability of CEA as an effective marker for lung cancer remains debatable, characteristics such as noninvasiveness and lack of other reliable markers make CEA an attractive option in lung cancer. Divergent CEA expression patterns before and after EGFR-tyrosine kinase inhibitor (TKI) treatment have been reported. However, whether these patterns are associated with tumor progression remain elusive. We hypothesized that divergent patterns of serum carcinoembryonic antigen at initial diagnosis (CEAIn) and disease progression (CEAPd) may reflect the diversity of lung cancer cells selected by TKI, conferring distinct progression profiles in patients. Our objective was to verify the prognostic potential of divergent CEA patterns before and after TKI treatment in lung cancer patients with wild-type or mutant EGFR. Of the 1736 lung cancer patients identified from the cancer registry group between 2011 to 2016, we selected 517 patients with advanced stage adenocarcinoma, data on EGFR mutation status and CEAIn, among whom were 288 patients with data on CEAPd, eligible for inclusion in the correlation analysis of clinical characteristics and survival. EGFR wild-type lung adenocarcinoma patients displayed lower CEAIn level than those with EGFR mutations. Multivariable analysis revealed that CEAIn expression was associated with poor progression-free survival in patients harboring mutant EGFR but not in those with wild-type EGFR. Moreover, CEAIn and CEAPd were associated with the good and poor post-progression survival, respectively, only in the EGFR-mutant and not in the wild-type group. In vitro cell line experiments revealed that CEA expression, cancer dissemination, and chemoresistant properties can be affected by EGFR-TKI selection. EGFR-mutant patients, exhibiting high CEAIn (≥ 5 ng/mL) and low CEAPd (&lt; 5 ng/mL), showed a potential toward displaying new metastasis. Our findings support the notion that EGFR mutation status is a critical factor in determining prognostic potential of CEAIn and CEAPd in patients under EGFR-TKI treatment, and divergent CEAIn and CEAPd patterns are associated with distinct cancer progression profiles.
Citation Format: Ming-Yi Zheng, Yen-Shou Kuo, Yu-Ting Chou. Prognostic potential of carcinoembryonic antigen expression patterns in lung adenocarcinoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6491.
Abstract 6499: Small slide, big world: Fast detection of altered proteins and RNA levels in clinical samples using Nanostring nCounter® GeoMxTM Digital Spatial Profiler
Authors: Gong Jingjing , Farren Matthew R. , Shaib Walid , Lesinski Gregory , Warren Sarah , Liang Yan 
Published: September 2020

Abstract
Although many new drugs have been approved and more clinical trials are being conducted for various disease therapies in recent decades, efficient identification of reliable therapeutic targets is still a big challenge during drug development. Therefore, tremendous efforts have been put into advancing the technology to quickly determine the altered biomarkers in clinical samples. Nanostring nCounter GeoMxTM Digital Spatial Profiling (GeoMx DSP) has been used in multiple projects and exhibited its outstanding performance on collecting analyzable digital counts for up-to 96 proteins and 20,000 RNAs in a specific area on a single FFPE slide. Tissue regions of interests are identified by fluorescent staining of morphology markers, and either proteins or RNAs in the specific defined regions are collected as the digital nCounter count format. By using this state-of-art technology, spatial distributions of immune- and cancer- relevant proteins were identified in 71 tumor cell rich-, 70 immune cell rich-, and 69 stromal cell rich- area respectively in three Pancreatic cancer patient groups including surgery alone, neoadjuvant FOLFIRINOX (a combination of fluorouracil, folinic acid, irinotecan and oxaliplatin) alone or combined with stereotactic body radiation therapy (F+SBRT). Our results showed that differential regulations among immune checkpoint markers, pan-immune markers and tumor markers in these treatment groups. In tumor-rich regions, CD44 is present at higher levels in FOLFIRINOX treated patients than surgery-alone group. VISTA was significantly down-regulated in F+SBRT group. Also, several key factors from pStat3, PTEN and Bcl2 pathways are also regulated by treatment methods. In immune-rich regions, both T cells markers (CD3 and CD4) and B cell markers (CD19 and CD20) were regulated differently by treatment methods. GeoMx DSP platform provides a novel and more precise view of the spatial regulation of micro-world in the tissue, which enable us to explore more about internal regulation within sub-population of the tissue cells.
GeoMxTM DSP platform is only for RESEARCH USE ONLY. Not for use in diagnostic procedures.
Citation Format: Jingjing Gong, Matthew R. Farren, Walid Shaib, Gregory Lesinski, Sarah Warren, Yan Liang. Small slide, big world: Fast detection of altered proteins and RNA levels in clinical samples using Nanostring nCounter® GeoMxTM Digital Spatial Profiler [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6499.