bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1540: Allogeneic chimeric antigen receptor T cells targeting B cell maturation antigen
Authors: Dar Henia , Henderson Daniel , Padalia Zinkal , Porras Ashley , Mu Dakai , Maeng Kyungah , Police Seshi , Kalaitzidis Demetrios , Terrett Jonathan , Sagert Jason 
Published: August 2018

Abstract
B cell maturation antigen (BCMA) is a tumor necrosis factor family cell surface receptor that binds B cell activating factor (BAFF) and a proliferation inducing ligand (APRIL) and is involved in the long-term survival of B cells. BCMA has been shown to be expressed broadly on monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM) cells and for this reason has been pursued as a potential antigen for the treatment of MM. Indeed, clinical studies evaluating autologous chimeric antigen receptor T cells (CAR-T cells) targeting BCMA for the treatment of MM have shown promising efficacy with &gt;80% response rates. However, logistical challenges will potentially limit the number of patients that have access to autologous therapies. Using the CRISPR/CAS9 system, we generated allogeneic CAR-T cells targeting BCMA by disrupting the beta-2-microglobulin (B2M) and T cell receptor alpha constant (TRAC) genes and inserting an anti-BCMA CAR into the TRAC locus. This results in allogeneic CAR-T cells lacking the major histocompatibility complex (MHC) and endogenous T cell receptor (TCR) expression while being potently cytotoxic towards cells expressing BCMA. These data show proof-of-concept for an “off the shelf” CAR-T therapy targeting BCMA.
Citation Format: Henia Dar, Daniel Henderson, Zinkal Padalia, Ashley Porras, Dakai Mu, Kyungah Maeng, Seshi Police, Demetrios Kalaitzidis, Jonathan Terrett, Jason Sagert. Allogeneic chimeric antigen receptor T cells targeting B cell maturation antigen [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1540.
Abstract 1549: LAPTM5 in clear cell renal cell carcinoma
Authors: Ryu Hyewon , Kim Solbi , Kim Nayoung , Kim Jin-Man , Lee Hyo Jin 
Published: August 2018

Abstract
Lysosomal-associated multispanning membrane protein 5 (LAPTM5) is membrane protein that mostly expressed in immune cells and hematopoietic cells. Recently, it has been demonstrated that LAPTM5 expression levels are decreased in several cancer cells by inducing regression of Hela cells and neuroblastomas. However, its exact role in cancer has yet to be defined. Furthermore, the clinical effect of LAPTM5 expression in cancer has not been reported so far. Thus, we investigated the association between LAPTM5 expression and its clinicopathological characteristics in 112 cases of clear cell renal cell carcinoma using tissue microarrays by immunohistochemical staining. Tumors were classified into four grades based on the staining intensity: 0 = no staining, +1 = weak, +2 = intermediate, and +3 = strong. The staining intensity was classified into LAPTM5-negative group or LAPTM5-positive groups. (0; negative, +1 ~ +3; positive). Of all 112 cases, 9 cases showed LAPTM5-negative, while 93 cases showed LAPTM5-positive: +1 (35 cases), +2 (28 cases), and +3 (30 cases). LAPTM5-positivity was significantly associated with decreased tumor recurrence. In addition, recurrence-free survival (RFS) (p = 0.010), cancer-specific survival (CSS) (p = 0.022), and overall survival (OS) (p = 0.022) were significantly decreased in the LAPTM5-negative group. Univariate analysis indicated that tumor size (HR = 3.44; 95% CI, 1.000-11.836), Fuhrman nuclear grade (HR = 1.863; 95% CI, 1.169-2.971), and negative LAPTM5 expression (HR = 3.173; 95% CI, 1.249-8.064) significantly affected the RFS of clear cell renal cell carcinoma patients. Moreover, CSS and OS were significantly affected by Fuhrman nuclear grade (HR = 2.177; 95% CI, 1.261-3.757 and HR = 1.673, 95% CI, 1.062-2.635, respectively) and negative LAPTM5 expression (HR = 3.398; 95% CI, 1.110-10.405 and HR = 2.826; 95% CI, 1.136-7.031, respectively). Multivariate analysis showed that a high Fuhrman nuclear grade and negative LAPTM5 expression were significant independent risk factors. Based on these results, loss of LAPTM5 was associated with poor oncological outcomes; this suggests that LAPTM5 might be a useful prognostic marker in patients with clear cell renal cell carcinoma.
Citation Format: Hyewon Ryu, Solbi Kim, Nayoung Kim, Jin-Man Kim, Hyo Jin Lee. LAPTM5 in clear cell renal cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1549.
Abstract 155: KDM4 inhibition targets breast cancer stem-like cells
Authors: Maurer Jochen 
Published: August 2018

Abstract
Traditional treatments for breast cancer fail to address therapy-resistant cancer stem-like cells that have been characterized by changes in epigenetic regulators such as the lysine demethylase KDM4. Here we describe an orally available, selective and potent KDM4 inhibitor (QC6352) with unique preclinical characteristics. To assess the antitumor properties of QC6352, we established a method to isolate and propagate breast cancer stem-like cells (BCSC) from individual triple-negative tumors resected from patients after neoadjuvant chemotherapy. Limiting-dilution orthotopic xenografts of these BCSC regenerated original patient tumor histology and gene expression. QC6352 blocked BCSC proliferation, sphere formation and xenograft tumor formation. QC6352 also abrogated expression of EGFR, which drives the growth of therapy-resistant triple-negative breast cancer cells. Our findings validate a unique BCSC culture system for drug screening and offer preclinical proof of concept for KDM4 inhibition as a new strategy to treat triple-negative breast cancer.
Citation Format: Jochen Maurer. KDM4 inhibition targets breast cancer stem-like cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 155.
Abstract 1551: Determination of the origin of oral squamous cell carcinoma by microarray analysis
Authors: Kinouchi Makoto , Izumi Sayaka , Uchida Daisuke , Kuribayashi Nobuyuki , Komiyama Yuske , Tsuchida Shuji , Fujita Atsushi , Kawamata Hitoshi 
Published: August 2018

Abstract
More than 90% of oral cancer is histopathologically squamous cell carcinoma (SCC). According to its clinical behavior and histopathological features, we hypothesize that oral SCC can originate from either oral squamous epithelium or the minor salivary glands. In this study, we attempted to clarify the possibility of some oral SCC originating from the minor salivary glands, and to investigate whether these tumors showed particularly aggressive biological behavior. The mRNA expression profile of samples obtained from 6 patients with SCC of the oral floor (5 men, 1 woman; mean age 62.7 years) was analyzed by microarray containing 32,878 genes. Clustering analysis of the expression level of the 845 genes that were differentially expressed in normal oral squamous epithelium and normal salivary glands revealed that the 6 samples can be divided into 2 groups. The expression profile in four cases was similar to that of normal oral squamous epithelium, and in two cases was similar to that of normal salivary glands. Furthermore, we identified nine genes that reveal the origin of the oral SCC. Subsequently, we examined the expression levels of these 9 marker genes by reverse transcriptase-polymerase chain reaction to determine the origin of 66 oral SCCs. Twelve of the 66 oral SCCs were considered to originate from minor salivary glands, and these tumors showed high metastatic potential (p&lt;0.05) and poor event free survival rate (p&lt;0.05). In conclusion, determination of the origin of the oral SCC is helpful when making a treatment plan for patients with oral SCC.
Citation Format: Makoto Kinouchi, Sayaka Izumi, Daisuke Uchida, Nobuyuki Kuribayashi, Yuske Komiyama, Shuji Tsuchida, Atsushi Fujita, Hitoshi Kawamata. Determination of the origin of oral squamous cell carcinoma by microarray analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1551.
Abstract 1559: Detection and retrieval of multiple myeloma cells with single-cell molecular confirmation from peripheral blood by multiparameter immunofluorescence, automated scanning, and image analysis
Authors: U'Ren Lance , Ericson Nolan , Campton Daniel , Ramirez Arturo , Blau C. Anthony , Kaldljian Eric 
Published: August 2018

Abstract
Background: The detection of multiple myeloma (MM) cells is currently performed by analysis of bone marrow aspirates. Detection of MM cells from the peripheral blood would allow for less invasive and more frequent assessments to monitor residual disease. Using the RareCyte platform, we developed a 5-parameter assay to visualize and retrieve MM cells from peripheral blood and applied it to MM patient samples under an IRB-approved protocol. We also used this to identify plasma cells from the peripheral blood of healthy volunteer donors.
Materials and Methods: Healthy volunteer or MM patient peripheral blood was collected into RareCyte blood collection tubes. RPMI8226 cells spiked into normal donor blood samples were used as a model for MM cell assay development. Buffy coats isolated from 7.5mL of blood by AccuCyte® separation were spread onto slides. Slides were stained with a 5-marker panel that included antibodies to CD138, CD38, CD56, CD45, and a nuclear dye on the Leica Bond Rx auto-stainer. Slides were scanned with CyteFinder® and MM cells identified by positive CD138 and CD56 staining and negative CD45 staining. Identified MM cells and WBC control cells were mechanically retrieved with the integrated CytePicker module, whole genome amplified, and Sanger sequencing was performed for specific mutations in four genes (IDH1, NRAS, PHLDA1, RPH3AL) identified by genomic analysis of a bone marrow sample. Plasma cells from normal donors were identified by co-expression of CD138 and CD38.
Results: In a pretreatment MM sample, the 5-parameter assay identified 55 MM cells per mL of whole blood. In isolated single cells with at least one successful sequencing reaction, 0 of 13 WBCs contained mutations in at least one of the genes. Mutations were found in 9 of 15 MM cells (defined as CD138+, CD56+, CD38-, and CD45-). In healthy volunteer samples, 5 plasma cells (defined as CD138+, CD38+, and CD45 dim/negative) were identified per mL of whole blood.
Conclusions: The 5-parameter assay successfully detected rare cells with an MM phenotype from the peripheral blood of an MM patient. Individually retrieved MM cells were demonstrated to contain mutations specific to the patient's tumor, confirming that the cells identified were MM cells. This approach may allow for less invasive assessment of MM and monitoring of residual disease.
Citation Format: Lance U'Ren, Nolan Ericson, Daniel Campton, Arturo Ramirez, C. Anthony Blau, Eric Kaldljian. Detection and retrieval of multiple myeloma cells with single-cell molecular confirmation from peripheral blood by multiparameter immunofluorescence, automated scanning, and image analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1559.
Abstract 156: Identifying novel therapeutics to inhibit the WNT self-renewal pathway in leukemia stem cells
Authors: Haney Meghan Green , Liu Chunming , Blackburn Jessica 
Published: August 2018

Abstract
The relapse rate of pediatric Acute Lymphoblastic Leukemia (ALL) is 15-20%, and these patients have limited treatment options and a poor prognosis. Relapse rate is likely due to a small population of cells known as leukemia stem cells (LSCs), which have the ability to self-renew and can re-form a leukemia from a single cell. Additionally, a major clinical concern is whether these LSCs are effectively killed by conventional cytotoxic chemotherapies. Current efforts to study LSCs have faced serious limitations, which have impeded our understanding of this important population of cells.
Prior work in our lab has established a zebrafish Myc-induced T-cell acute lymphoblastic leukemia (T-ALL) model that mimics the most aggressive and treatment resistant form of human T-ALL. Using this system, we isolated single LSCs through a novel transplantation strategy. Limiting dilution analysis showed significant differences in the rate of self-renewal between different LSCs, suggesting heterogeneity in LSC relapse potential. We generated a library of zebrafish T-ALL with high self-renewal rates (about 1 in 10 leukemia cells is a LSC) for use in bulk RNAseq, as well as single cell qPCR and single cell RNAseq to identify a self-renewal signature unique to LSCs. Single cell analyses showed a population of cells that expressed known self-renewal genes and clustered separately from the rest of the leukemia cells in the population. Ongoing work in our laboratory is focused on functionally testing whether this gene expression profile is linked with self-renewal. Additionally from this analysis, the Wnt pathway, more specifically ß-catenin, was enriched in the putative LSC population. These data support previous findings in mammalian models of ALL.
We hypothesize that inhibitors of the Wnt pathway will inhibit self-renewal of LSCs and force them to terminally differentiate. However, there are no WNT inhibitors clinically available due to undesirable side-effects. We are currently using a 6xTCF/LEF:GFP zebrafish Wnt reporter model for high-throughput screens to identify new, less toxic Wnt pathway inhibitors. Thus far, several compounds have showed significantly decreased TCF/LEF activity after drug treatment, with no effects on animal health. Future studies will test these inhibitors in our zebrafish high LSC leukemia samples and patient derived xenograft models. Ultimately, these inhibitors may represent a potential therapeutic strategy for targeting treatment-resistant LSCs and preventing ALL relapse.
Citation Format: Meghan Green Haney, Chunming Liu, Jessica Blackburn. Identifying novel therapeutics to inhibit the WNT self-renewal pathway in leukemia stem cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 156.
Abstract 1568: Advancing convergence and innovation in cancer research: National Cancer Institute Center for Strategic Scientific Initiatives (CSSI)
Authors: Elder Sarah G. , Lee Jerry S. , Berny-Lang Michelle A. , Hanlon Sean E. 
Published: August 2018

Abstract
Since 2003, the National Cancer Institute's Center for Strategic Scientific Initiatives (CSSI) has worked to develop the resources and infrastructures investigators need to surmount roadblocks in cancer research. To this end, CSSI manages programs that promote technology development and cross-disciplinary collaboration and provide support for investigators in nascent and challenging research fields. This support includes funding opportunities, shared reagent and database resources, and assistance in the development of standards and protocols. CSSI also provides a network of partners in industry and government that can help NCI-funded researchers advance their technologies toward commercialization and translation. This presentation will highlight technologies including single-cell isolation and analysis techniques that have been supported through various CSSI mechanisms from proof of concept to translation into the clinic.
Citation Format: Sarah G. Elder, Jerry S. Lee, Michelle A. Berny-Lang, Sean E. Hanlon. Advancing convergence and innovation in cancer research: National Cancer Institute Center for Strategic Scientific Initiatives (CSSI) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1568.
Abstract 1570: Loss of mismatch repair protein MSH6 sensitizes diffuse-type gastric cancer cells to DNA-PKcs inhibitor KU60648
Authors: Krishnan Vaidehi , Lau Wen Min , Teng Eileen , Tan Jin Wei , Sankar Haresh , Lim Debbie Xiu En , Pang Crystal Kok Yan , Teh Ming , So Jimmy Bok Yan , Tan Patrick , Ito Yoshiaki , Chan Shing Leng 
Published: August 2018

Abstract
Diffuse-type gastric cancer (DGC) is a histologic subtype characterized by poor cellular cohesiveness, increased metastasis and poor prognosis. As preclinical models of DGC that reliably predict clinical activity of novel compounds are lacking, we generated patient-derived xenograft (PDX) models using malignant ascites from DGC patients that closely recapitulated the primary cancer. To uncover novel therapeutic targets, we applied the concept of synthetic lethality and asked if DGCs require DNA repair proteins for survival. Major DNA repair kinases ATM, ATR and DNA-PKcs in established DGC cell lines and ex vivo cell lines from PDXs (GAGA3, GAGA6 and GAS24) were inhibited using small-molecule inhibitors KU55933, VE-821 and KU60648, respectively. Interestingly, most diffuse-type gastric cells exhibited elevated lethality when DNA-PKcs, a central kinase that regulates the non-homologous end joining pathway (NHEJ), was inhibited by KU60648 as compared to the nontransformed gastric epithelial line, HFE-145. We confirmed that genetic depletion of DNA-PKcs by siRNA resulted in cell death in two PDX lines GAS24 and GAGA6 cells but not in HFE-145 cells, suggesting the dependence of these cells on DNA-PKcs for survival. Two mechanisms appear to sensitize DGC cells to DNA-PKcs inhibition; firstly, impaired homologous recombination repair in GAS24 and GAGA6 as shown by compromised ability to resolve radiation-induced γH2AX foci, and secondly, transcriptional downregulation of the mismatch repair protein, MSH6, in GAGA3 and GAGA6. Knockdown of MSH6 in GAS24 cells enhanced their sensitivity to KU60648, suggesting a functional link between MSH6 and DNA-PK function. Lastly, to develop MSH6 as a biomarker for predicting DNA-PKcs sensitivity, we analyzed MSH6 levels by immunohistochemical staining in formalin-fixed, paraffin-embedded (FFPE) tissue sample sections derived from PDXs. In these preliminary studies, MSH6 expression was lower with high heterogeneity in GAGA3 and GAGA6 compared to GAS24. In this study, we show for the first time the downregulation of DNA mismatch protein MSH6 in sporadic diffuse gastric cancer, and its potential as a therapeutic predictor for DNA-PKcs inhibition treatment.
Citation Format: Vaidehi Krishnan, Wen Min Lau, Eileen Teng, Jin Wei Tan, Haresh Sankar, Debbie Xiu En Lim, Crystal Kok Yan Pang, Ming Teh, Jimmy Bok Yan So, Patrick Tan, Yoshiaki Ito, Shing Leng Chan. Loss of mismatch repair protein MSH6 sensitizes diffuse-type gastric cancer cells to DNA-PKcs inhibitor KU60648 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1570.
Abstract 1572: The value of p16 or HPV as predictive marker of anti-EGFR treatment in recurrent/metastatic HNSCC
Authors: Lim Joo Han , Hong Soon-Sun , Kim Jin-Chul , Lee Moon Hee , Cho Jinhyun 
Published: August 2018

Abstract
Introduction: The anti-epidermal growth factor receptor (EGFR) agent was approved and has been a mainstay of treatment of recurrent/metastatic head and neck squamous cell cancers (HNSCC). However, it is unclear whether human papilloma virus (HPV) modulates the response to targeting the EGFR. Some subset analysis of the randomized phase III study is confusing and recent The Cancer Genome Atlas data showed that EGFR gene is rarely abnormal in HPV-positive HNSCC tumors while it is frequently altered in HPV-negative HNSCC tumors. The purpose of our meta-analysis is to evaluate the effects of anti-EGFR agents regarding HPV status.
Materials and Methods: We conducted a pooled analysis to evaluate the association of p16 expression status with outcomes in patients with recurrent/metastatic HNSCC receiving palliative anti-EGFR treatment with or without chemotherapy. A literature search of PubMed, EMBASE, and meeting abstracts of the American Society of Clinical Oncology and European Society of Medical Oncology through December 2017 was conducted.
Results: A total of seven trials met the selection criteria. The total number of patients was 700 (554 with the HPV-negative group and 146 with the HPV-positive group). Anti-EGFR treatment was associated with higher response rate in p16-negative patients compared with in p16-positive patients (OR 2.18; 95% CI, 1.18-3.99, p=0.01).
Conclusion: A meta-analysis of trials with anti-EGFR agents in p16-negative RMHNSCC patients versus in p16-positive recurrent/metastatic HNSCC patients yielded that p16 status could be a predictive biomarker for anti-EGFR treatment in recurrent/metastatic HNSCC. Prospective study is warranted to determine the value of p16 or HPV as a predictive marker of anti-EGFR treatment in recurrent/metastatic HNSCC.
Citation Format: Joo Han Lim, Soon-Sun Hong, Jin-Chul Kim, Moon Hee Lee, Jinhyun Cho. The value of p16 or HPV as predictive marker of anti-EGFR treatment in recurrent/metastatic HNSCC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1572.
Abstract 1573: A clinical biomarker assay to quantitate MIP-1a in human serum
Authors: Wong Li Chin , Wong Oitak , Laterza Omar F. , Zhao Xuemei 
Published: August 2018

Abstract
Macrophage inflammatory protein 1-alpha (MIP-1alpha, MIP-1α, CCL3) is a cytokine that is involved in the acute inflammatory state in recruitment and activation of polymorphonuclear leukocytes through binding to the receptors CCR1, CCR4 and CCR5. MIP-1α is expressed by macrophages, dendritic cells and lymphocytes. Crucial in immune response against infection and inflammation, MIP-1α induces the synthesis and release of IL-6, IL-10 and TNFα. As a proinflammatory chemokine, MIP-1α is primarily associated with cell adhesion and migration of monocytes to inflammatory tissues. In addition, MIP-1 α inhibits the proliferation of hematopoietic stem cells in vitro and in vivo. Expression levels of MIP-1 α have provided important information in the progression of diseases such as multiple myeloma, lung cancer, multiple sclerosis, HIV infection, allergic asthma and sepsis.
Citation Format: Li Chin Wong, Oitak Wong, Omar F. Laterza, Xuemei Zhao. A clinical biomarker assay to quantitate MIP-1a in human serum [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1573.