bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5681: Utility of a targeted NSCLC genomic test for cfDNA variants in the community setting
Authors: Hahn Westen , Thurston Scott , Jackson Leisa , Weaver Amanda , Tschida Cherie , Sage Brent , Alexander Kristin , Pelletier Tunee , Charrington Nia , Cooper Samantha , Marr Dianna , Bowling Paul M. , Mellert Hestia , Pestano Gary 
Published: July 2017

Abstract
Time to treatment can have significant impact on progression of cancer, and treatment decisions rely heavily upon genomic and proteomic testing. However, multiple factors can delay the availability of molecular diagnostic test results, including the use of tissue-based testing. Almost one third of patients with non-small cell lung cancer (NSCLC) are either not candidates for biopsies, or have insufficient tissue samples from their initial biopsy. Additionally, most physicians in the community setting want to initiate treatment quickly but do not have access to on-site molecular testing at their practice. As a result, physicians may delay their decision to commence treatment with specific targeted therapies or treat before the mutation status is known. The goal of this study was to assess the utility of a blood-based cell-free (cf) nucleic acid Laboratory Developed Test (LDT) in the community setting. The tests utilize Droplet Digital™ PCR (ddPCR) technology to detect the EGFR sensitizing mutations L858R and exon 19 deletion (E746 - A750), the EGFR resistance mutation (T790M), the KRAS mutations G12C, G12V and G12D, and the BRAF V600E mutation. Patient samples for testing were collected and shipped at ambient room temperature using a Biodesix® whole blood sample collection kit and processed at the Biodesix laboratory. Metrics were reviewed from the real-time measurement of established molecular diagnostic markers in the plasma of patients with NSCLC. For this study we analyzed results from greater than 4,000 patient cases (~24,000 individual variants). Greater than 70% of test orders were received from physician practices that self-identified as community based. Test mutation status results were reported within 72 hours of sample receipt from the physician’s office (95%). The percentage of tests requested that were positive for each variant category were 9% for EGFR sensitizing, 9% for EGFR resistance, 11% for KRAS, and 1% for BRAF. Notably, we generated test results successfully for 98% of tests submitted. We have developed fast, highly robust and sensitive blood-based assays to expedite time to treatment and expand the laboratory testing options for patients with NSCLC.
Citation Format: Westen Hahn, Scott Thurston, Leisa Jackson, Amanda Weaver, Cherie Tschida, Brent Sage, Kristin Alexander, Tunee Pelletier, Nia Charrington, Samantha Cooper, Dianna Marr, Paul M. Bowling, Hestia Mellert, Gary Pestano. Utility of a targeted NSCLC genomic test for cfDNA variants in the community setting [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 5681. doi:10.1158/1538-7445.AM2017-5681
Abstract 5691: ESR1 methylation in plasma cfDNA of patients with high-grade serous ovarian cancer
Authors: Giannopoulou Lydia , Mastoraki Sophia , Strati Areti , Chebouti Isaam , Kasimir-Bauer Sabine , Lianidou Evi S. 
Published: July 2017

Abstract
Introduction: ESR1 methylation is frequently observed in many types of solid malignancies, but few studies attempted to investigate ESR1 methylation status in ovarian cancer so far. We examined for the first time ESR1 methylation in plasma samples of high-grade serous (HGSC) ovarian cancer patients, using a novel real-time MSP assay.
Materials and methods: We first developed and validated a highly specific and sensitive real-time MSP assay for ESR1 methylation. A commercially available 100% methylated standard was used as positive control in all experiments. We then evaluated ESR1 methylation in plasma (2mL) of 59 pre-surgery, mainly advanced stage HGSC patients. A control group of 51 plasma samples from healthy women was recruited for the evaluation of specificity of our assay. All cfDNA samples isolated from plasma were subjected to sodium bisulfite (SB) treatment and were then analyzed by real-time MSP for ESR1 methylation. For the normalization of the results, we used ACTB as a reference gene. The real-time PCR assay for ACTB was designed to amplify specifically SB treated DNA.
Results: The real-time MSP assay is highly sensitive, as it detects down to 0.1% of ESR1 methylation in the presence of 99.9% non-methylated sequences. ESR1 methylation was detected in 18/59 (30.5%) high-grade serous ovarian patients, but only in 1/51 (2.0%) of healthy women. All results were obtained after normalization with ACTB as a reference gene.
Conclusion: We report for the first time that ESR1 methylation can be detected in cfDNA of high-grade serous ovarian cancer patients, but not in healthy women. Further investigation is required to determine the clinical significance of ESR1 methylation status in cfDNA of HGSC patients. We also aim to evaluate our findings in a larger group of patients.
Citation Format: Lydia Giannopoulou, Sophia Mastoraki, Areti Strati, Isaam Chebouti, Sabine Kasimir-Bauer, Evi S. Lianidou. ESR1 methylation in plasma cfDNA of patients with high-grade serous ovarian 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 5691. doi:10.1158/1538-7445.AM2017-5691
Abstract 5718: Outcome prediction in colorectal cancer using digitized tumor samples and machine learning
Authors: Bychkov Dmitrii , Turkki Riku , Haglund Caj , Linder Nina , Lundin Johan 
Published: July 2017

Abstract
Additional prognostic stratification of colorectal cancer patients is needed to improve management of patients. Visual microscopic assessment of tumor samples remains the standard method for disease subtyping. However, visual analysis of samples is subjective and weakly reproducible due to inter- and intra-observer variations. Recent progress within machine learning, especially its novel branch called deep learning, enables accurate evaluation of complex patterns observed in microscopic tissue images. Here, we combined deep learning techniques to evaluate a set of digitized formalin fixed paraffin embedded hematoxylin-eosin stained tumor tissue microarray (TMA) samples from 420 randomly selected patients with colorectal cancer. For each patient a set of clinicopathological characteristics including histological grade, Dukes stage and age at diagnosis are available as well as outcome data. Using convolutional neural networks and Long Short-Term Memory networks we validated the predictive power of the colorectal TMAs with regards to patient outcome. Univariate Cox proportional hazard regression analysis demonstrated that the prognostic accuracy of the deep learning algorithm on TMAs (hazard ratio 2.3; CI 95% 1.79-3.03) outperforms visual histological grading performed by a certified pathologist on a whole slide level (hazard ratio 1.65; CI 95% 1.30-2.15). In multivariate Cox proportional hazard regression, the deep learning based model was a prognostic factor, independent of histological grade, Dukes stage and age at diagnosis (Wald p-value &lt; 0.001). Thus, we demonstrate that novel deep learning models can serve as digital prognostic biomarkers in colorectal cancer.
Citation Format: Dmitrii Bychkov, Riku Turkki, Caj Haglund, Nina Linder, Johan Lundin. Outcome prediction in colorectal cancer using digitized tumor samples and machine learning [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 5718. doi:10.1158/1538-7445.AM2017-5718
Abstract 5725: Search for a combination of risk stratification markers for recurrence after curative resection of gastric cancer
Authors: Oshima Takashi , Miyagi Yohei , Kimura Yayoi , Sakamaki Kentaro , Yamanaka Shoji , Oue Naohide , Aoyama Toru , Sato Tsutomu , Cho Haruhiko , Shiozawa Manabu , Yoshikawa Takaki , Rino Yasushi , Yasui Wataru , Imada Toshio , Masuda Munetaka 
Published: July 2017

Abstract
Objective: Adjuvant chemotherapy after curative resection is standard treatment for stage II/III gastric cancer. Personalized therapy based on biomarker analysis is expected to further improve outcomes. We analyzed frozen specimens of gastric cancer to investigate markers for stratification of recurrence risk and report our findings.
Methods: We studied 778 patients with stage II/III gastric cancer in whom ≥5 years had elapsed since curative resection. We first measured the expression levels of 127 genes in gastric cancer tissue by quantitative polymerase-chain-reaction (PCR) assay in 255 patients (training set, 145; validation set, 110) to identify poor prognostic factors. Next, we studied patients who received 1 year of adjuvant chemotherapy after curative resection of T4a, Nx, M0, stage III gastric cancer and performed an exploratory proteomic analysis to compare the expressions of 1756 proteins between 12 patients who died of recurrence within 3 years and 12 patients who survived with no recurrence for at least 5 years. Proteins with a max fold change of &gt;2 and significant differences (P&lt;0.001) were identified. Immunostaining of tissue microarray sections from another cohort of 499 patients was performed to confirm our results and to identify combinations of markers for risk stratification.
Results: On quantitative PCR assay, SPARC, HER2, CXCR4, INHBA, VSNL1, MMP11, CCR7, MRP1, CEACAM7, p53, EZH2, PDGFRB, and VCAM1 were identified as candidate markers. On exploratory proteomic analysis, SPARC, CLC, PRG2, and PRG3 were identified. A tissue microarray was constructed for the 16 candidate markers to evaluate combinations of markers. The combination of SPARC, EZH2, HER2, and p53 could be used for risk stratification (5-year survival rate, 68% vs. 33%; P=0.0111).
Conclusions: The combination of SPARC, EZH2, HER2, and p53 can be used as a marker to stratify the risk of recurrence after curative resection of stage II/III gastric cancer.
Citation Format: Takashi Oshima, Yohei Miyagi, Yayoi Kimura, Kentaro Sakamaki, Shoji Yamanaka, Naohide Oue, Toru Aoyama, Tsutomu Sato, Haruhiko Cho, Manabu Shiozawa, Takaki Yoshikawa, Yasushi Rino, Wataru Yasui, Toshio Imada, Munetaka Masuda. Search for a combination of risk stratification markers for recurrence after curative resection of gastric 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 5725. doi:10.1158/1538-7445.AM2017-5725
Abstract 5743: Characterization of mitochondrial DNA mutations and tumor evolution in ulcerative colitis-associated colorectal cancer
Authors: Baker Kathryn Terese , Nachmanson Daniela , Kennedy Scott R. , Brentnall Teresa A. , Risques Rosa Ana 
Published: July 2017

Abstract
The role of mitochondrial DNA (mtDNA) mutations in cancer is highly controversial. While specific mtDNA mutations have been associated with certain cancers, it has been recently reported that mtDNA mutations are negatively selected in most tumors. We aimed to clarify the role of mtDNA mutations in cancer progression by: 1) capitalizing on the multi-step sequence of tumorigenesis in ulcerative colitis (UC), a premalignant disease ideal for the study of tumor progression, and 2) employing a highly accurate, ultra-deep sequencing method to fully characterize the mtDNA mutational profile at different stages of tumor evolution. UC is an inflammatory bowel disease characterized by chronic colonic inflammation that increases the risk of colorectal cancer (CRC). UC CRC evolves through a stepwise process that involves the accumulation of molecular alterations in otherwise histologically normal epithelium, low-grade dysplasia (LGD), high-grade dysplasia (HGD), and cancer. Our lab has previously identified mitochondrial alterations as a facet of dysplastic progression in UC. Here we have worked to fully characterize the spectrum and frequency of mtDNA mutations in UC tumorigenesis by applying a novel, highly sensitive NGS technology, Duplex Sequencing (DS), that can accurately detect mutant allele frequencies (MAF) as low as 0.01%. For two patients that developed cancer, we analyzed 15-20 colon biopsies obtained at colectomy, representing all stages of tumorigenesis. The median duplex sequencing depth was 4,000x, which allowed unprecedented resolution to detect subclonal mutations (MAF 1-99%) and rare mutations (MAF&lt;1%). Several subclonal mutations were present in all biopsies, but with variable MAF, thus enabling construction of phylogenetic trees via PHYLIP analysis. Rare mutations were abundant in all biopsies; on average one in every 10,000 nucleotides sequenced was mutated. Most rare mutations were G to A transitions, indicative of replicative errors, but G to T and C to A transversions, the oxidative damage mutational signature, were prevalent in some biopsies. We conclude, therefore, that most mtDNA mutations are caused by proliferation with a contribution by inflammatory processes, and that this may have greater implications for their role in other cancer types.
Citation Format: Kathryn Terese Baker, Daniela Nachmanson, Scott R. Kennedy, Teresa A. Brentnall, Rosa Ana Risques. Characterization of mitochondrial DNA mutations and tumor evolution in ulcerative colitis-associated colorectal 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 5743. doi:10.1158/1538-7445.AM2017-5743
Abstract 5749: VCAN promotes clear cell renal cell carcinoma tumor progression and metastasis, and predicts poor prognosis
Authors: Mitsui Yozo , Kato Taku , Maekawa Shigekatsu , Hashimoto Yutaka , Shiina Marisa , Sumida Mitsuho Imai , Wong Ryan Kenji , Yamamura Soichiro , Shahryari Varahram , Majid Shahana , Saini Sharanjot , Deng Guoren , Dahiya Rajvir , Nakajima Koichi , Tanaka Yuichiro 
Published: July 2017

Abstract
Introduction and Objectives: Although versican (VCAN) is known to promote tumor progression and enhance metastasis of several types of cancers, its role in clear cell renal cell carcinoma (ccRCC) remains unknown. Interestingly, a recent report showed that VCAN is an important target of chromosomal 5q gain, one of the most prevalent genetic abnormalities in ccRCC cases. In the present study, we investigated whether VCAN expression is associated with the pathogenesis of ccRCC.
Methods: VCAN expression was analyzed in 3 RCC and normal kidney cell lines, as well as 84 matched ccRCC and normal renal tissues. We also performed various functional analyses of growth and progression properties using VCAN-depleted ccRCC cells. Microarray analysis was then employed to investigate the target genes of the pathway involved in ccRCC tumorigenesis and development.
Results: There are 4 isoforms of VCAN containing the N-terminal globular (G1 domain) and C-terminal globular (G3 domain) domains, each of which was found to be over-expressed in the ccRCC samples as compared to the controls. Higher VCAN expression was significantly correlated with metastasis (p&lt;0.001) and worse 5-year overall survival after a radical nephrectomy (p=0.014). In vitro, VCAN knockdown by siRNA in Caki-2 and 786-O cells significantly decreased cell proliferation and increased apoptosis, and was also found to be associated with alteration of several TNF signaling-related genes, such as TNF-α, BID, and BAK. Furthermore, VCAN depletion markedly decreased cell migration and invasion associated with reduced MMP7 and CXCR4 levels.
Conclusion: Our results demonstrate that VCAN promotes ccRCC tumorigenesis and metastasis, showing it to be an attractive novel target for diagnostic, prognostic, and therapeutic strategies for affected patients.
Note: This abstract was not presented at the meeting.
Citation Format: Yozo Mitsui, Taku Kato, Shigekatsu Maekawa, Yutaka Hashimoto, Marisa Shiina, Mitsuho Imai Sumida, Ryan Kenji Wong, Soichiro Yamamura, Varahram Shahryari, Shahana Majid, Sharanjot Saini, Guoren Deng, Rajvir Dahiya, Koichi Nakajima, Yuichiro Tanaka. VCAN promotes clear cell renal cell carcinoma tumor progression and metastasis, and predicts poor prognosis [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 5749. doi:10.1158/1538-7445.AM2017-5749
Abstract 5779: Building a novel 3D hyaluronan-based tri-culture model of the bone metastatic microenvironment for cancer studies
Authors: Sablatura Lindsey K. , Harrington Daniel A. , Farach-Carson Mary C. 
Published: July 2017

Abstract
The high attrition rate of potential anti-cancer drugs entering clinical trials predicates a need for more predictive pre-clinical model systems. Three-dimensional (3D) culture systems provide cells a more physiological microenvironment than traditional cell culture methods—including relevant extracellular matrix (ECM) cues and cell-cell interactions—while allowing greater experimental control and higher-throughput studies than animal models. Prevalent cancers, including breast and prostate cancer, metastasize preferentially to bone, where they become incurable. The bone marrow microenvironment is a complex network of interacting bone homeostatic and hematopoietic niches that contribute to osteotropic cancer homing, proliferation, and treatment resistance. We created a 3D in vitro tri-culture model of the bone metastatic microenvironment to serve as a new platform to study the “trialogue” between bone metastatic cancer, bone marrow stroma, and bone marrow endothelial cells. This tool can be used to inform drug discovery and to combat treatment resistance. Within the present study, the utility of peptide-functionalized hyaluronan hydrogels for supporting the self-organization of 3D bone marrow microvascular networks was explored. Gel crosslinking density was varied to examine the effect of matrix porosity on cell migration and organization over time. Tubule length and diameter were quantified and the endothelial structures were assessed for indicators of mature vasculature, including lumen formation, basement membrane production, and the recruitment of supporting stromal cells. Breast/prostate cancer cell growth, survival, and physical association with bone marrow stromal and bone marrow microvascular endothelial cell networks was examined in tri-culture models. Ongoing studies seek to identify and disrupt key cell signaling pathways that mediate cell-cell interaction and promote cancer cell proliferation and survival, providing new tools to combat bone metastatic disease.
Citation Format: Lindsey K. Sablatura, Daniel A. Harrington, Mary C. Farach-Carson. Building a novel 3D hyaluronan-based tri-culture model of the bone metastatic microenvironment for cancer studies [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 5779. doi:10.1158/1538-7445.AM2017-5779
Abstract 5791: 3D tissue engineering bladder model for cancer invasion study
Authors: Goulet Cassandra Ringuette , Bernard Geneviève , Chabaud Stéphane , Pouliot Frédéric , Bolduc Stéphane 
Published: July 2017

Abstract
INTRODUCTION: Our understanding of the biological processes involved in bladder cancer (BCa) is greatly limited by the models currently available. In fact, the combination of in vitro and in vivo models of BCa has failed to elucidate all the fundamental aspects of the disease. The eighth most commonly diagnosed cancer in Western societies, BCa has become a growing public health concern, and more realistic models are needed to reveal the mechanisms involved in tumor initiation and progression. METHODS: Bladder substitutes have been constructed by tissue engineering with healthy human fibroblasts and urothelial cells, using the self-assembly method. Meanwhile, spheroids have been produced from non-invasive (RT4) and invasive (T24) BCa cell lines expressing DsRed fluorescent protein. The invasive potential of these spheroids was characterized in a type-I collagen gel (2.5mg/mL). Then, the spheroids were implanted on the surface of bladder substitutes, after which their development was followed by fluorescence microscopy. RESULTS: Both of the cancer cell lines used were able to form compact spheroids and grow on bladder equivalents. The invasive behaviour of spheroids varied depending on the nature of the cells used. The non-invasive RT4 cell line was unable to cross the basal lamina whereas the invasive T24 cell line was able to do so. CONCLUSION: The establishment of such a model for studying cancer biology in a physiological environment will help bridge the gap between overly simple cell culture models and more complex transgenic mice models. This new model offers a unique opportunity to study separately the players involved in the development of BCa and thus represents a powerful tool for the mechanistic analysis of this complex pathology.
Citation Format: Cassandra Ringuette Goulet, Geneviève Bernard, Stéphane Chabaud, Frédéric Pouliot, Stéphane Bolduc. 3D tissue engineering bladder model for cancer invasion 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 5791. doi:10.1158/1538-7445.AM2017-5791
Abstract 5800: Epidermal growth factor-induced ANGPTL4 enhances anoikis resistance and tumor metastasis in head and neck squamous cell carcinoma
Authors: Liaong Yu-Han 
Published: July 2017

Abstract
Epidermal growth factor (EGF) is important for cancer cell proliferation, angiogenesis and metastasis in many types of cancer. However, the mechanisms involved in EGF-induced head and neck squamous cell carcinoma (HNSCC) metastasis remain largely unknown. In this study, we reveal that angiopoietin-like 4 (ANGPTL4) plays an important role in the regulation of EGF-induced cancer metastasis. We showed that EGF-induced ANGPTL4 expression promoted anoikis resistance and cancer cell migration and invasion in head and neck squamous cell carcinoma (HNSCC). In addition, depletion of ANGPTL4 inhibited EGF-induced cancer cell invasion. Autocrine production of EGF-induced ANGPTL4 regulated the expression of MMPs. The induction of MMP-1 gene expression by ANGPTL4-activated integrin β1 signaling occurred through the AP-1 binding site in the MMP-1 gene promoter. Furthermore, down-regulation of MMP-1 impeded EGF- and recombinant ANGPTL4-enhanced HNSCC cell migration and invasion. Depletion of ANGPTL4 significantly blocked EGF-primed anoikis resistance and extravasation. Moreover, depletion of ANGPTL4 significantly blocked EGF-primed metastatic seeding of tumor cells and MMP-1 expression in lungs. However, no effect of ANGPTL4 on tumor growth was observed. These results suggest that EGF-induced expression and autocrine production of ANGPTL4 enhances HNSCC metastasis via the up-regulation of MMP-1 expression. Inhibition of ANGPTL4 expression may be a potential strategy for the treatment of EGFR-mediated HNSCC metastasis.
Citation Format: Yu-Han Liaong. Epidermal growth factor-induced ANGPTL4 enhances anoikis resistance and tumor metastasis in head and neck squamous cell 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 5800. doi:10.1158/1538-7445.AM2017-5800