bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5233: Pancreatic cancer specific glycosylations survay by a panel of lectin staining; Tn antigen exposure as a result of o-glycan truncation
Authors: Ozawa Yusuke , Oda Tatsuya , Shimomura Osamu , Tateno Hiroaki , Hirabayashi Jun , Ohkohchi Nobuhiro 
Published: July 2017

Abstract
The outermost coating of every cell type is predominantly composed of cell-specific glycans, and glycosylation changes in cancer has been used in clinical field as a tumor markers, such including AFP and CA19-9. We focused pancreatic cancer, the most intractable cancer with difficulty in early diagnosis, and insisted to glasp glycosylation patterns by using a panel of lectin histochemical stainings. Lectins are subgroup of proteins that specifically recognize and bind glycans, and thus helpful indication of glycosylation patterns. Lectin microarry is one of the advanced technologies which inables glycosylation patters of target materials at onece, however, obtained data with homogenized protein matelials applied lacks histological location and information. Instead, we used a panel of 20 types of lectins histochemical staining for cancer and normal tissues. The staining patterns were firstlly classified according to the ratio between cancer cells and stromal cells. a) Cancer high (cancer cell ++ and stromal cells -) b) equal (cancer cells ++ or + and stromal cells ++ or +) c) Cancer Low (cancer cells - or + and stromal cells ++ or +). Further more, the stainig in cancer cell were compaired with that of non cancerous pancreatic ductal epitherial cells. Among 20 lectins, CNL, Clitocybe nebularis Lectin binds motifs containing α/βGalNAc, Tn antigen, and blood group A, showed cancer cell staining higher than normal tissue in pancreatic cancer. Pancreatic cancer cell (31 of 58 patients,71%) were positive for CNL, but normal pancreatic duct cells (2 of 42 patients,4%) were positive in patients of pancreatic cancer. CNL is known to recognize Tn Antigen in O-glycosylation. Previously, it reported that during malignancy, glycosylation displays abnormal expression of shortened or truncated glycans, such as a Tn antigen, T antigen and their sialylated forms, ST, STn antigen. CNL staining pattern we showed in this report is considered to matching Tn staining. Our result indicated that speccific affinity of CNL lectin in pancreatic cancer and counterpart glycoprotein are STn antigen. We may insist that STn glycoprotein antigen could be used as a diagnostic marker of Pancreatic cancer and also it would be a target of new tumor-targetting strategies.
Citation Format: Yusuke Ozawa, Tatsuya Oda, Osamu Shimomura, Hiroaki Tateno, Jun Hirabayashi, Nobuhiro Ohkohchi. Pancreatic cancer specific glycosylations survay by a panel of lectin staining; Tn antigen exposure as a result of o-glycan truncation [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 5233. doi:10.1158/1538-7445.AM2017-5233
Abstract 5281: Komen Tissue Bank donors: Genetically determined ethnicity and race
Authors: McCarty Julia R. , Jiang Guanlong , Johnson Mariah L. , Mahin Teresa , Scherer Nicholas , Dunn Jonathon , Storniolo Anna Maria , Marino Natascia 
Published: July 2017

Abstract
Background: Several evidences indicate that different racial and ethnic backgrounds affect the incidence and severity of diseases such as breast cancer and diabetes, and the response to therapy. For example White and African American women are more likely to develop breast cancer than Hispanic and Asian women. Moreover, African American women are more likely to develop more aggressive (Triple Negative Breast Cancer), more advanced-stage breast cancer at a young age. Therefore, given the health disparity and with the advance of personalized medicine, it is becoming critical to address population stratification. The Komen Tissue Bank at IU Simon Cancer Center (KTB), the only biobank of normal breast tissue from healthy women, is employing a more accurate approach to detect population stratification through the use of Ancestry Informative Markers (AIMs).
Methodology: A total of 2,973 DNA samples were obtained from the KTB. Genotyping was performed using the KASP technology (LGC Genomics) and a 41-SNP panel (labeled 41-AIM panel) selected from Nievergelt et al, 2013. Genotype analysis using the 41-AIM panel along with a Bayesian clustering method (STRUCTURE) was able to discern continental origins including European/ Middle East (Caucasian), East Asia, Central/South Asia, Africa, Americas, and Oceania. A reference set was obtained from the HeatMap. The results were compared with the self-reported data.
Results/Conclusion: Our genetic ancestry analysis indicates that out of 2,973 KTB tissue donors, 2,132 are primarily Caucasian, 532 African, 234 of Asian, 72 Latino, 3 Oceanic origins. High mixture of racial markers was observed in several samples. Moreover, when we compare these findings with the self-reported data we find a 10.9% of discrepancies indicating the imprecision of the self-reported information. The implementation of the genetic ancestry data into the KTB creates the potential for a more accurate study of health disparities.
Citation Format: Julia R. McCarty, Guanlong Jiang, Mariah L. Johnson, Teresa Mahin, Nicholas Scherer, Jonathon Dunn, Anna Maria Storniolo, Natascia Marino. Komen Tissue Bank donors: Genetically determined ethnicity and race [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 5281. doi:10.1158/1538-7445.AM2017-5281
Abstract 5296: Evaluation of p16/Ki-67 dual stain, cytology, and HPV16/18 genotyping for triage of HPV-positive women in a large screening population
Authors: Wentzensen Nicolas A. , Fetterman Barbara , Bremer Renee , Castle Philip , Tokugawa Diane , Poitras Nancy , Hosfield Elizabeth , Lorey Thomas , Schiffman Mark , Kinney Walter 
Published: July 2017

Abstract
Objectives: Primary HPV testing has been approved in the United States. Screening intervals can be safely extended for HPV-negative women, but the challenge lies in discriminating transient HPV infections from precancers among HPV-positives. In a large study at Kaiser Permanente Northern California (KPNC), candidate strategies for triage of HPV-positive women are being evaluated, including cytology, p16/Ki-67 dual stain (DS, CINtec PLUS) and HPV16/18 genotyping (cobas).
Methods: Over 13,000 HPV-positive women participating in cervical cancer screening at KPNC were enrolled. The dual stain and HPV genotyping assays were implemented and conducted at KPNC. Baseline results for 7,124 women are available and detection of CIN3 is currently evaluated only in cytology-positive women.
Results: Among 7,124 HPV-positive women, 4,107 (57.7%) were cytology-positive (ASC-US+), 3,056 (42.9%) were DS-positive, and 1,406 (19.7%) were positive for HPV16 or HPV18. Among all 3,017 HPV-positive, cytology-negative women, 911 (30.2%) were DS- positive, and 508 (16.8%) were positive for HPV16 or HPV18. Of 315 CIN3 detected so far, 280 (88.9%) were DS-positive and 176 (55.9%) were positive for HPV16 or HPV18. Major triage strategies including cytology alone, DS alone, as well as combinations of cytology and genotyping, and DS and genotyping will be presented at the meeting.
Discussion: In one of the largest clinical implementation studies of triage strategies, we showed that primary HPV screening followed by DS can reduce colposcopy referral compared to HPV-cytology co-testing while achieving high sensitivity. Additional follow-up is underway to evaluate the programmatic performance of several major candidate strategies.
Citation Format: Nicolas A. Wentzensen, Barbara Fetterman, Renee Bremer, Philip Castle, Diane Tokugawa, Nancy Poitras, Elizabeth Hosfield, Thomas Lorey, Mark Schiffman, Walter Kinney. Evaluation of p16/Ki-67 dual stain, cytology, and HPV16/18 genotyping for triage of HPV-positive women in a large screening population [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 5296. doi:10.1158/1538-7445.AM2017-5296
Abstract 5327: Glioma derived cancer stem cells are hypersensitive to proteasomal inhibition
Authors: Lee Dae-Hee , Oh Sang Cheul , Kwon Yong Tae , Lee Yong J. , Yoo Young Dong 
Published: July 2017

Abstract
Although proteasome inhibitors (PIs) are used as anticancer drugs to treat various cancers, their relative therapeutic efficacy on stem cells vs. bulk cancers remains unknown. Here, we show that stem cells derived from gliomas, GSCs, are up to 1,000-fold more sensitive to PIs (IC50, 27-70 nM) compared with their differentiated controls (IC50, 47-&gt;&gt;100 µM). The stemness of GSCs correlates to increased ubiquitination, whose misregulation readily triggers apoptosis. PI-induced apoptosis of GSCs is independent of NFκB but involves the phosphorylation of JNK as well as the transcriptional activation of endoplasmic reticulum (ER) stress-associated proapoptotic mediators. In contrast to the general notion that ER stress-associated apoptosis is signaled by prolonged unfolded protein response (UPR), GSC-selective apoptosis is instead counteracted by the UPR. ATF3 is a key mediator in GSC-selective apoptosis. Pharmaceutical uncoupling of the UPR from its downstream apoptosis sensitizes GSCs to PIs in vitro and during tumorigenesis in mice. Thus, a combinational treatment of a PI with an inhibitor of UPR-coupled apoptosis may enhance targeting of stem cells in gliomas.
Key words: glioma; glioma stem cells; proteasome inhibitors; ubiquitin proteasome system; apoptosis; c-Jun N-terminal kinase (JNK)
Citation Format: Dae-Hee Lee, Sang Cheul Oh, Yong Tae Kwon, Yong J. Lee, Young Dong Yoo. Glioma derived cancer stem cells are hypersensitive to proteasomal inhibition [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 5327. doi:10.1158/1538-7445.AM2017-5327
Abstract 5358: Comprehensive evaluation of Illumina’s TruSight® Tumor 170 Panel to estimate tumor mutational burden
Authors: Zhang Shile , So Alex S. , Kaplan Shannon , Kruglyak Kristina M. 
Published: July 2017

Abstract
Tumor mutational burden (TMB), or the density of variants in a tumor, is typically assessed by whole exome sequencing (WES) and has been shown to correlate with efficacy of immunotherapy treatment. Targeted cancer gene panels are broadly used to assess mutational status in cancer related genes but have not historically been used to estimate TMB. Recently, two studies have demonstrated that TMB can be accurately estimated using these cancer gene panelsi,ii. Illumina’s TruSight® Tumor 170 (TST170, research use only, RUO) panel is a comprehensive next-generation sequencing (NGS) assay that covers the coding regions of 170 genes associated with solid tumors. TST170 targets DNA and RNA variants from the same FFPE tumor sample in a single sequencing run. Here we evaluate the performance of TMB estimation with TST170.
TST170 is an enrichment-based targeted panel designed to capture mutational changes, including single nucleotide variant, indels, amplifications, splice variants and fusions. The TST170 analysis pipeline is able to call variants with frequencies down to 5%. In the current study, TMB was calculated as the number of reported variants per megabase after germline polymorphism filtering. First, we evaluated the performance of TST170 for TMB estimation using 6,000 TCGA samples that had been analyzed by WES. TMB estimated from the TST170 targeted regions showed a high correlation to TMB estimated from WES (R2=0.91). Next, we evaluated the prognostic value of TMB estimated from TST170 by overlapping the TST170 targeted regions with WES data for 202 subjects treated with CTLA-4 or PD-1 from three clinical studies. Higher TMB estimated from the TST170 targeted regions was observed in subjects who responded to checkpoint inhibitors. Finally, we assessed the correlation of TMB estimation using matched samples profiled with both WES and TST170 and again saw high correlation between the two methods. In summary, our analysis indicates that the panel content of TST170 can be used to accurately estimate TMB from tumor samples.
i Garofalo A, Sholl L, Reardon B, et al. The impact of tumor profiling approaches and genomic data strategies for cancer precision medicine. Genome Med. 2016;8(1):79. doi:10.1186/s13073-016-0333-9.
ii Campesato, L., Barroso-Sousa, R., Jimenez, L., et al. Comprehensive cancer-gene panels can be used to estimate mutational load and predict clinical benefit to PD-1 blockade in clinical practice. Oncotarget, 2015;6(33), 34221-34227.
Citation Format: Shile Zhang, Alex S. So, Shannon Kaplan, Kristina M. Kruglyak. Comprehensive evaluation of Illumina’s TruSight® Tumor 170 Panel to estimate tumor mutational burden [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 5358. doi:10.1158/1538-7445.AM2017-5358
Abstract 5464: Catalase mediates the survival of anchorage-independent ovarian cancer cells
Authors: Libbing Cassandra L. , Versagli Calli A. 
Published: July 2017

Abstract
Among United States women, ovarian cancer is the fifth leading cause of cancer-related death and the deadliest of the female reproductive system cancers. This is due to a lack of early detection, in effect, leading to primary diagnosis in later, metastasized stages for which there are few effective treatment options. In order to metastasize, ovarian cancer cells must be able to survive detachment from the extracellular matrix (ECM). When a non-tumorigenic mammary epithelial cell detaches from the ECM, research has shown that levels of Reactive Oxygen Species (ROS) rise in the cell and inhibit cell metabolism resulting in decreased cell survival. Previous research has also shown that ECM-detached breast cancer cells are able to utilize antioxidant enzymes to neutralize ROS thereby rescuing ATP levels and promoting cell survival. This antioxidant activity has also been shown to bolster cancer cells’ survival in anchorage independence. Although studied in breast cancer cells, no work has been done in ovarian cancer, which exhibits a very unique mode of metastasis through the peritoneal fluid. To begin to understand the role of antioxidant enzymes in metastatic ovarian cancer cells, we have worked to characterize the role of catalase, a prominent antioxidant enzyme, in the survival of ECM-detached SKOV3 ovarian cancer cells. In order to do so, we utilized short hairpin RNA (shRNA) to engineer SKOV3 cells deficient in catalase. The catalase-deficient cells were then tested for colony formation in detachment and cell viability and proliferation in both attachment and detachment. The results show that elimination of catalase expression does not have a significant effect on proliferation in attachment or detachment, but significantly decreases both cell viability and colony formation of SKOV3 cells grown in ECM-detachment. This suggests that elimination of catalase expression may hold promise for targeted treatment in late stage ovarian cancer, calling for further investigation of the mechanisms behind these results and the role that other antioxidant enzymes play in ovarian cancer. Future studies include looking at this phenomenon in other ovarian cancer cell lines, and using mouse xenograft studies to examine the effects of antioxidant compounds on survival of metastatic ovarian cancer cells.
Citation Format: Cassandra L. Libbing, Calli A. Versagli. Catalase mediates the survival of anchorage-independent ovarian cancer 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 5464. doi:10.1158/1538-7445.AM2017-5464
Abstract 5481: Role and regulation of Peroxiredoxin antioxidant proteins in K562 leukemia cells
Authors: Szabo Elizabeth , Phelan Shelley A. 
Published: July 2017

Abstract
Peroxiredoxins are a family of antioxidant proteins that have found to play a key role in many diseases, including cancer. A wide number of studies have found that Peroxiredoxin levels are elevated in several cancers, and reducing these levels can aid in inhibiting cell growth of cancer cells, suggesting that Peroxiredoxins confer resistance to reactive oxygen species (ROS)-induced cellular toxicity in cancer cells. Specific research has demonstrated that Peroxiredoxin levels are elevated in leukemia cells, and that targeting and inhibiting Peroxiredoxins in these cells can induce differentiation. Studies have also shown the use of doxorubicin as an effective chemotherapy treatment to significantly decrease cell proliferation and viability in leukemia. The purpose of this study is to examine Peroxiredoxin levels in K562 cells, a human chronic myelogenous leukemia cell line, and determine if high levels of Peroxiredoxins have the ability to protect cells from chemotherapy-induced death and possibly aid in chemoresistance. We first demonstrated that serum-deprived K562 cells exhibited significant growth inhibition over a 72 hour time period, but had no significant effect on viability. We also showed that treating K562 cells with 50 nM doxorubicin significantly decreased proliferation and viability. Corresponding changes in Peroxiredoxin protein levels are currently being analyzed to determine the effect of both growth-inhibition and chemotherapy-induced cytotoxicity on the Peroxiredoxin family in K562 cells, and siRNA experiments are being conducted to examine the protective role of Peroxiredoxins in these cells. Based on previous studies on MCF-7 cells conducted in our lab, we predict that Peroxiredoxin levels will be modified under both conditions, and that suppression of Prdxs by siRNA will increase chemotherapy susceptibility.
Citation Format: Elizabeth Szabo, Shelley A. Phelan. Role and regulation of Peroxiredoxin antioxidant proteins in K562 leukemia 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 5481. doi:10.1158/1538-7445.AM2017-5481
Abstract 5507: Investigation of the effects of alterations in the glutamate receptor, GRIK2 on osteosarcoma tumorigenesis
Authors: Mayers Justin G. , Gokgoz Nalan , Wunder Jay S. , Andrulis Irene L. 
Published: July 2017

Abstract
Osteosarcoma is a primary, malignant bone tumour mainly affecting young adults with a five-year survival rate of 60-70% depending on presentation of metastasis at diagnosis. Tumours are marked by genetic instability and heterogeneity and for this reason, molecular subtypes have yet to be characterized. Survival rates have remained consistent over the past few decades and novel molecular targets for treatment are needed. Current genomic strategies have identified recurrent copy number alterations. In a study of 44 flash frozen osteosarcoma tumours which were obtained at the time of biopsy and 25 blood-matched samples we identified recurrent copy number losses including a region at 6q16.3 in 14% of tumours. Focal deletions were observed in the 5’ intergenic space and first intron of the GRIK2 gene and do not overlap with any coding sequence. The relationship between alterations in this region and osteosarcoma tumourigenesis has yet to be explored in depth. GRIK2 encodes an ionotropic glutamate receptor that has been implicated as a tumour suppressor in gastric cancer. An interesting feature of the tumours was the overlap of focal deletions with a SETDB1 histone methyltransferase binding site indicating a potential connection with epigenetic regulation of GRIK2. The goal of this study is to examine the effects of non-coding, focal deletions on GRIK2 gene expression, function and regulation in osteosarcoma cells. GRIK2 transcript levels were measured in osteosarcoma tumours and cell lines using qRT-PCR. Functional assays were performed to characterize the role of GRIK2 in osteosarcoma cell proliferation, migration and apoptosis in vitro. Gene editing with CRISPR/cas9 was performed to examine the link between non-coding deletions and GRIK2 expression. GRIK2 transcript levels varied in tumours; several tumours with focal deletions had increased transcript levels relative to cell lines which demonstrated low expression levels. Due to the observation of low transcript levels, a gain of function approach was employed to examine GRIK2 function in vitro. Overexpression of GRIK2 decreased proliferation, migration and increased apoptosis in osteosarcoma cells. Gene editing of the SETDB1 binding site resulted in increased GRIK2 transcript levels relative to untreated cells. This study suggests that non-coding focal deletions are linked to high expression levels of GRIK2 which may confer a less aggressive phenotype and are involved in epigenetic regulation of the gene.
Citation Format: Justin G. Mayers, Nalan Gokgoz, Jay S. Wunder, Irene L. Andrulis. Investigation of the effects of alterations in the glutamate receptor, GRIK2 on osteosarcoma tumorigenesis [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 5507. doi:10.1158/1538-7445.AM2017-5507