bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3453: Cancer Cell Line Factory: A systematic approach to create next-generation cancer model at scale
Authors: Tseng Yuen-Yi , AI-Jazrawe Mushriq , Deasy Rebecca , Keskula Paula , Johnson Grace , Hong Andrew , Chatterji Priya , Vasquez Francisca , Bass Adam , Van Hare Barbara , Sandak David , Ligon Keith , Boehm Jesse 
Published: September 2020

Abstract
Precision cancer medicine is based on the ability to predict the dependencies of a given tumor from its molecular makeup. Despite successes in multiple common cancers, such prediction remains challenging for the majority of rare and understudied tumors given the absence of laboratory model systems in which to discover and/or validate therapeutic hypotheses. Here, we describe our efforts to address this challenge systematically with the ultimate goal of making it possible to learn how to predict ex vivo growth requirements for cancer samples based on technical, clinical and genomic properties of the starting tumor material. Over the last 5 years, we have processed nearly 2,000 tumor biospecimens and created over 375 genomically-confirmed patient-derived cell lines, organoids and neurosphere cultures, with &gt;10% of these representing rare cancers. To make this possible, we have implemented three key workflows including (1) direct-to-patient sample sourcing, (2) a tissue cryopreservation and genomic credentialing system to ensure quality prior to model creation, and (3) a systematic empirical approach to screening rich medias and variations on organoid technologies ex vivo (HYBRID). We have begun performing genome-wide CRISPR viability screens in these cultures as part of our larger activities to generate a systematic laboratory-based functional map of cancer dependencies (a ‘Cancer Dependency Map'). The novel organoid, spheroid and cell line models created as part of this effort are being made publically available to the scientific community. Looking ahead, as the barriers to culturing rare tumors are overcome, we expect that preclinical functional genomics data will be useful for difficult-to-treat tumors without existing molecularly guided standard-of-care regimens.
Citation Format: Yuen-Yi Tseng, Mushriq AI-Jazrawe, Rebecca Deasy, Paula Keskula, Grace Johnson, Andrew Hong, Priya Chatterji, Francisca Vasquez, Adam Bass, Barbara Van Hare, David Sandak, Keith Ligon, Jesse Boehm. Cancer Cell Line Factory: A systematic approach to create next-generation cancer model at scale [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 3453.
Abstract 347: Neogenin as an anti-invasive target for diffuse intrinsic pontine gliomas
Authors: Sesen Julie , Driscoll Jessica , Smith Edward 
Published: September 2020

Abstract
Introduction. Diffuse Intrinsic Pontine Glioma (DIPG) is a rare high-grade tumor of the brainstem that occurs almost exclusively in children. The significant mortality rates of DIPG stem largely from its capacity to invade adjacent normal brain. We have previously published studies identifying the axon guidance factor netrin-1 and its receptor neogenin as key drivers regulating brain tumor invasion in medulloblastoma and glioblastoma. Here we expand this work to investigate the role of netrin-1 and neogenin in DIPG and identify them as putative biomarkers and governors of tumor invasion.
Methods. Urine of 49 DIPG patients and 42 age- and sex-matched controls was collected. Netrin-1 expression was quantified by ELISA. Results were subjected to univariate and multivariate statistical analyses and compared between clinical cohorts. In vitro experiments with established DIPG cell lines utilized RTqPCR, Western blot and flow cytometry to quantify expression of netrin-1 and neogenin. The effect of neogenin blockade on viability and invasion was assessed by flow cytometry (n=3) and transwell chamber assays (n=3) respectively.
Results. Patient samples revealed a significantly low level of urinary netrin-1 compared to matched controls (p&lt;0.005). This result was corroborated with cell lines in vitro. Interestingly, its receptor neogenin was upregulated in these cells when compared to control glial cells when quantified by mRNA, protein and FACS analysis. Blockade of neogenin in DIPG cell lines resulted in an increase of cell death and a significant decrease of cell invasion.
Conclusion. Expanding on previous work, this data suggests that urinary levels of netrin-1 may have utility as a non-invasive biomarker for DIPG. Our data demonstrates the vital role of neogenin as a regulator of tumor invasion and survival in DIPG. The blockade of neogenin in DIPG cells also demonstrates the potential utility of neogenin as a cell-surface druggable target, capable of reducing tumor invasion and increasing tumor cell death.
Citation Format: Julie Sesen, Jessica Driscoll, Edward Smith. Neogenin as an anti-invasive target for diffuse intrinsic pontine gliomas [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 347.
Abstract 3501: Lower perceived colorectal cancer risk is associated with less aerobic physical activity in Latino adults
Authors: Agrawal Pooja , Yanez Jocelyn , Murillo Rosenda 
Published: September 2020

Abstract
INTRODUCTION: Engaging in aerobic physical activity (PA) has been linked to reduced risk of adverse health outcomes, such as colorectal cancer (CRC). Despite known benefits of engaging in aerobic PA, Latino adults have a low prevalence of aerobic PA compared to other racial/ethnic groups. Limited research has examined the relationship between perceived risk of CRC and aerobic PA among Latinos. Therefore, the purpose of our study was to examine perceived risk of CRC and aerobic PA among US Latino adults.
METHODS: We used cross-sectional 2015 National Health Interview Survey (NHIS) data on Latino participants ≥18 years of age (n=5,457). Perceived CRC risk was assessed based on self-reported measures to which participants responded whether they considered themselves at less than average risk, average risk, or higher than average risk for CRC. Aerobic PA was measured based on self-reported minutes of moderate-to-vigorous aerobic activity per week, which were categorized into none (0 min/week), some aerobic PA (&gt;0 min/week of activity but less than recommendation), and meeting the aerobic activity guideline (≥150 min of moderate-vigorous PA or ≥75 min of vigorous PA or 150 min of moderate PA/week). Multinomial logistic regression models that accounted for complex survey design of NHIS were used to estimate the associations between perceived risk of CRC (ref= less than average risk) with aerobic PA (ref= none). All models were adjusted for age, sex, education, insurance, and nativity.
RESULTS: In adjusted models, compared with individuals who perceived themselves at higher than average risk, those who perceived themselves at less than average risk for CRC were significantly less likely to engage in some aerobic activity (Odds Ratio [OR]: 0.63, 95% Confidence Interval [CI]: 0.40-0.99). In addition, those who perceived themselves at average risk for CRC were also significantly less likely to engage in some aerobic activity (OR 0.60, 95% CI: 0.37-0.96).
CONCLUSION: These findings suggest that perceived CRC risk is associated with aerobic activity among Latino adults. CRC prevention efforts should consider the role of perception of CRC risk in the promotion of physical activity among Latinos.
Citation Format: Pooja Agrawal, Jocelyn Yanez, Rosenda Murillo. Lower perceived colorectal cancer risk is associated with less aerobic physical activity in Latino adults [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 3501.
Abstract 3527: Paraneoplastic glomerulonephropathies associated with solid tumor: A review of published literature
Authors: Zhang Xiaojie , Paul Asit K. 
Published: September 2020

Abstract
Background: Paraneoplastic glomerulonephropathies (PGN) are paraneoplastic syndromes associated with solid tumors and hematologic malignancies. PGN is difficult to differentiate from other forms of glomerulonephropathies and standard management of glomerulonephropathies is often ineffective. A delay in diagnosis may lead to significant morbidity and mortality. To date, no retrospective or prospective data on PGN have been published. We reviewed clinical variables, treatment, and outcome in published case reports of PGN associated with solid tumors over the past three decades.
Methods: We conducted a search to identify published case reports on solid tumors associated with PGN in English PubMed-indexed journals. Keywords used included: “solid tumor”, “lung cancer”, “gastrointestinal cancer”, “gynecological cancer”, “genitourinary cancer”, “paraneoplastic nephropathy,” “paraneoplastic glomerulopathy,” “minimal change disease,” “IgA nephropathy,” “membranoproliferative,” “membranous,” “nephropathy” and “glomerulonephropathy”. Published articles from January 1st, 1987 to November 30,2019 were screened. Included were the patients who had laboratory and/or biopsy proven nephrotic syndrome in association with a solid tumor diagnosis.
Results: We identified 95 patients who fulfilled the inclusion criteria. The median age of the patients were 58 years. The majority of the patients were male (65%). Among them, 37 (39%) were diagnosed with PGN prior to the diagnosis of cancer. Membranous nephropathy (41%) was the most common subtype, followed by minimal change disease (17%), focal segmental glomerulonephritis (14%) and IgA nephropathy (11%). Genitourinary cancers (36%) followed by lung cancers (30%), gastrointestinal cancers (15%) and gynecological cancers (13%) are the common cancers associated with PGN. Among the patients, 44 (46%) had non-metastatic tumors, 39 (41%) had metastatic tumors and 12 (13%) were unspecified. Treatment information were available for 79 of 95 (83%) patients. Overall, PGN improved in 76% of patients who received definitive or systemic therapy with or without steroid compared to 57% of patients who were treated with steroid alone. Definitive and systemic treatment alone led to improvement of PGN in 24 of 29 (83%) patients without metastasis and 13 of 17 (76%) patients with metastasis.
Conclusions: PGNs associated with solid tumors are rare and can happen in both non-metastatic and metastatic cancers. Diagnosis of PGN might precede the diagnosis of cancer. Definitive or systemic anticancer therapies improved PGN in most cases and were more effective than steroid alone.
Citation Format: Xiaojie Zhang, Asit K. Paul. Paraneoplastic glomerulonephropathies associated with solid tumor: A review of published literature [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 3527.
Abstract 3530: Investigating aneuploidy, CIN and mechanisms of DNA content reduction in cancer
Authors: Mandelia Mara , Drosopoulos Kostas , Linardopoulos Spiros 
Published: September 2020

Abstract
Chromosomal instability (CIN) is a form of genomic instability that refers to a dynamic state in which the cells are constantly changing the number and/or the structure of their chromosomes. CIN leads to aneuploidy, a state in which a cell's set of chromosomes deviates from the euploid set. Causes of aneuploidy include errors during DNA replication, mitosis and cell fusion events. Furthermore, aneuploidy has been shown to promote tumorigenesis and tumor progression, but also to reduce cell fitness or induce cell death, especially when high levels of aneuploidy are present. Nevertheless, antimitotic drugs that induce high levels of aneuploidy, such as Paclitaxel, are not always effective in the clinic.
In this study, we aim to investigate the mechanisms by which cancer cells tolerate aneuploidy, to elucidate the mechanisms by which cell fusion can lead to aneuploidy and resistance to paclitaxel and to identify new targets in aneuploidy and CIN.
Towards this direction, aneuploid clones of pseudo-diploid cancer cells were generated after treatment with anti-mitotic drugs and single cell sorting and were characterized by cell cycle profile, metaphase spreads and CGH or SNP profile. Furthermore, CIN was induced by inhibition of CENP-E or ATM or impairment of the SWI/ SNF complex and quantified by induction of chromosome missegregation and micronuclei formation.
Interestingly, several near tetraploid clones that were isolated after anti-mitotic drug treatment, reduced their DNA content to near diploid during propagation in culture. Thus, we hypothesize that cancer cells may utilize specific mechanisms to change their DNA content and maintain tolerable levels of aneuploidy. By time-lapse microscopy, we observed that cells treated with Paclitaxel, can increase their DNA content by abortive mitosis, cytokinesis failure or by undergoing cell fusion. Interestingly, these multinucleated cells could reduce their DNA content by undergoing independent mitosis, independent nucleus catastrophe or independent nucleus separation (cell exodus). We identify cell exodus, as a potential mechanism by which cells can recover after treatment with Paclitaxel. Inhibition of ROCK pathway, that stabilizes actin filaments and prevents cellular contractility, reduced cell fusion and exodus events and delayed cell recovery after paclitaxel treatment.
Finally, in order to identify new targets in CIN and aneuploidy, we setup sgRNA loss of function screening conditions in the generated CIN and aneuploid cell models and we aim to identify genes that are essential for the survival of aneuploid and/or CIN cancer cells.
Citation Format: Mara Mandelia, Kostas Drosopoulos, Spiros Linardopoulos. Investigating aneuploidy, CIN and mechanisms of DNA content reduction in 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 3530.
Abstract 3563: Fatty acid binding protein 7 regulates beige fat-like differentiation of breast cancer cells and thermogenesis
Authors: Kawashima Masahiro , Bensaad Karim , Zois Christos , Barberis Alessandro , Bridges Esther , Lagerholm Christoffer , Dmitriev Ruslan I. , Toi Masakazu , Papkovsky Dmitri B. , Buffa Francesca , Harris Adrian L. 
Published: September 2020

Abstract
Cancer cells alter the metabolism in their microenvironment to sustain their survival, growth and progression. Heat is an essential factor that can affect metabolism. However, it is unclear whether cancer cells can alter their temperature by regulating heat production. Non-shivering thermogenesis is known to takes place in inducible beige adipocytes expressing the mitochondrial thermogenic protein, uncoupling protein 1 (UCP1). UCP1 dissipates the proton gradient of the mitochondrial inner membrane and converts its energy into heat. We found that the inhibition of a hypoxia-inducible protein, fatty acid binding protein 7 (FABP7), triggered beige fat-like differentiation and induced thermogenesis in breast cancer cells. We established the breast cancer cell line with a stable knockdown of FAPB7, using lentivirus transduction particles. UCP1-expressing cells were found in 21 ± 5% of the knockdown cells while they were found in only 4 ± 1.7% of the control cells: p = 0.004). UCP1 expression was maximized in the knockdown cells when cultured in hypoxia. A novel thermo-sensitive fluorescent probe confirmed that the cellular temperature of the knockdown cells was 2°C higher than the controls. In addition, the knockdown cells exhibited the increased mitochondrial depolarization, increased proton leak and increased respiration rate compared to controls, suggesting they had the similar energy profile with beige adipocytes. The knockdown cells became more sensitive to hypoxia and radiation, and the clinical manifestation of breast cancer patients differed depending on the expression levels of both UCP1 and FABP7. These observations suggested a missing link between hypoxia-related fatty acid metabolism and cellular thermogenesis which might be a novel therapeutic target for breast cancer.
Citation Format: Masahiro Kawashima, Karim Bensaad, Christos Zois, Alessandro Barberis, Esther Bridges, Christoffer Lagerholm, Ruslan I. Dmitriev, Masakazu Toi, Dmitri B. Papkovsky, Francesca Buffa, Adrian L. Harris. Fatty acid binding protein 7 regulates beige fat-like differentiation of breast cancer cells and thermogenesis [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 3563.
Abstract 361: Pleckstrin-2 as a prognostic factor and mediator of gastric cancer progression
Authors: Sun Bo , Xiang Jian-Bin , Xuan Yi , Chen Zong-You , Gu Xiao-Dong , Xu Da-Zhi 
Published: September 2020

Abstract
Background: Pleckstrin-2 (PLEK2) is a crucial mediator of cytoskeletal reorganization. However, the potential roles and clinical significance of PLEK2 in gastric cancer are still unknown.
Methods: We aimed to illustrate the function of PLEK2 in gastric cancer. Pearson's correlation analysis was utilized to test the clinical impacts of the levels of PLEK2 in gastric cancer patients. Loss-of-function approaches were used to estimate the potential roles played by PLEK2 in modulating gastric cancer proliferation, self-renewal, and tumourigenicity. Immunoblotting and bioinformatics approaches were used to monitor the effect of PLEK2 on epithelial-mesenchymal transition (EMT) signalling pathways.
Results: In gastric cancer tissue samples examined by western blot and real-time PCR, there was an increased level of PLEK2 compared with that in matched non-tumour samples. Kaplan-Meier plotter analysis revealed that gastric cancer patients with higher PLEK2 levels had substantially poorer overall survival (p=0.0028) compared with gastric cancer patients with lower PLEK2 levels. The upregulation or downregulation of PLEK2 in gastric cancer cell lines effectively enhanced or inhibited cell proliferation and pro-invasive behaviour, respectively. Additionally, we also found that PLEK2 enhanced EMT concomitantly with a reduction in E-cadherin and an elevation in Vimentin.
Conclusions: Our findings demonstrated that PLEK2 plays a potential role in gastric cancer and may act as a prognostic factor for gastric cancer.
Citation Format: Bo Sun, Jian-Bin Xiang, Yi Xuan, Zong-You Chen, Xiao-Dong Gu, Da-Zhi Xu. Pleckstrin-2 as a prognostic factor and mediator of gastric cancer progression [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 361.
Abstract 3689: Mutation spectrum of MEF cells transformed by overexpression of novel activating KRAS mutation candidates in lung adenocarcinoma
Authors: Abe Jiro , Tanuma Nobuhiro , Nomura Miyuki , Ito Shin , Kasugai Isao , Sato Ikuro , Tamai Keiichi , Mochizuki Mai , Yamaguchi Kazunori , Shima Hiroshi , Okada Yoshinori , Yasuda Jun 
Published: September 2020

Abstract
Lung adenocarcinoma (LUAC) is a unique lung cancer subtype that is responsive to several therapeutic agents. The KRAS gene is the second most frequently mutated gene in LUAC and the majority of KRAS mutations are one of three classical activating mutations (G12, G13, and Q61). Recently, we have characterized other types of “minor” KRAS mutation (A66T, A66V, and G75E) identified among LUAC patients and found these three mutants had tumor-forming activity in mouse embryonic fibroblasts in an allograft model. RNA-Seq analysis revealed that mouse embryonic fibroblasts overexpressing these three minor KRAS mutations have distinct expression profiles compared with overexpression of the wild type but similar expression profiles compared with overexpression of the classical KRAS mutants, G12V. In this study, we have searched candidate somatic genetic alterations in the RNA-seq data and will discuss the impact of the mutations in KRAS carcinogenesis.
Citation Format: Jiro Abe, Nobuhiro Tanuma, Miyuki Nomura, Shin Ito, Isao Kasugai, Ikuro Sato, Keiichi Tamai, Mai Mochizuki, Kazunori Yamaguchi, Hiroshi Shima, Yoshinori Okada, Jun Yasuda. Mutation spectrum of MEF cells transformed by overexpression of novel activating KRAS mutation candidates 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 3689.
Abstract 3707: Transcriptional downregulation of microRNA 199a-1 in the tumor microenvironment confers chemoresistance and stemness in ovarian cancer cells
Authors: Hassan Ayon A. , Yang Zhenyu , Shum Ho-Cheung , Lai Hung-Cheng , Wong Alice S. 
Published: September 2020

Abstract
The tumor microenvironment is actively involved in cancer progression and is becoming an attractive therapeutic target. It is increasingly clear that both biotic and abiotic factors in the microenvironment play a crucial role in disease progression. Using a three-dimensional microfluidic platform that mimics the peritoneum, we previously demonstrated that physiologically relevant shear-stress can induce chemoresistance and stemness in ovarian cancer cells. Importantly, this mechanical stimulus resulted in downregulation of microRNA (miR)199a-3p, suggesting a previously unknown mechanosensitive property of this miRNA. In testing other microenvironmental factors known to be involved in ovarian cancer progression in the regulation of miR-199a-3p, we found that hepatocyte growth factor (HGF), which is abundant in malignant ascites, could decrease miR-199a-3p expression in a similar manner to shear stress. Both shear stress and HGF induced this downregulation through a transcriptional regulation of primary mir-199a-1, but not primary mir-199a-2, via a PI3/Akt signaling pathway. Using metanalysis, there was also a decrease of miR-199a-3p in patients' tumor samples, and an increase of Akt in high-risk group. Moreover, ectopic overexpression of primary mir-199a-1 could sensitize ovarian cancer cells to cisplatin and reduce their ability to form multicellular spheroids, confirming a role for this miRNA in chemoresistance and stemness. Taken together, our findings suggest a causal involvement of downregulation of primary mir-199a-1, and ultimately its mature counterpart miR-199a-3p, in the tumor microenvironment mediated induction of stemness and chemoresistance, and represents a potential therapeutic target for the treatment of ovarian cancer (This work is supported by HMRF 05163536).
Citation Format: Ayon A. Hassan, Zhenyu Yang, Ho-Cheung Shum, Hung-Cheng Lai, Alice S. Wong. Transcriptional downregulation of microRNA 199a-1 in the tumor microenvironment confers chemoresistance and stemness in ovarian cancer cells [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 3707.