bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4896: Transcriptomic alterations by HPV-human fusion transcripts in HPV+ HNSCC cell lines
Authors: Pinatti Lisa M. , Sinha Hana , Brenner Chad , Walline Heather M. , Carey Thomas E. 
Published: September 2020

Abstract
Human papillomavirus (HPV) genomic integration is frequently seen in oropharyngeal squamous cell carcinoma (OPSCC). Integration into cellular genes can cause the generation of HPV-host fusion transcripts, which have been associated with altered gene expression of critical cellular pathways and worse survival in OPSCC patients. The mechanism of these transcriptomic alterations by fusion transcripts and how they contribute to poor outcome are unknown. We began our analysis by investigating whether our cell lines models of HPV+ OPSCC recapitulate these gene expression alterations using a qRT-PCR profiling system. We compared the expression of 128 genes in relevant pathways in four fusion transcript positive cell lines versus two fusion transcript negative cell lines and found a number of genes that were differentially expressed between the two groups. This suggests that these cell lines are appropriate models to study the mechanism of fusion transcript-dependent transcriptional regulation. To confirm our results in another system, we created fusion transcript positive/negative cell lines by cloning two pairs of either an HPV-human fusion transcript or an HPV only transcript into normal keratinocytes. These cloned cells were then run through the same qRT-PCR profiling system, and we saw differentially expressed genes between the two groups. There was an overlapping set of gene pathways between the HPV+ OPSCC cell lines and cloned keratinocytes, suggesting HPV-human fusion transcripts are sufficient to alter cellular gene expression. Subsequent in-depth molecular characterization and in vitro studies will help clarify the mechanism of these changes and their effects on cancer formation and metastasis. These studies will advance our understanding of how fusion transcripts lead to worse patient survival and help develop new therapies for these patients.
Citation Format: Lisa M. Pinatti, Hana Sinha, Chad Brenner, Heather M. Walline, Thomas E. Carey. Transcriptomic alterations by HPV-human fusion transcripts in HPV+ HNSCC cell lines [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 4896.
Abstract 4897: Genome-wide structural variation analysis and characterization of Hepatitis B Virus integration sites in hepatocellular carcinomas using Bionano Genomics whole genome imaging
Authors: Hong Karl , Péneau Camille , Bayard Quentin , Imbeaud Sandrine , Pang Andy , Hastie Alex , Letouzé Eric , Zucman-Rossi Jessica 
Published: September 2020

Abstract
Large genomic rearrangements are known contributors to cancer formation. Hepatitis B virus (HBV) integration is a frequent driver of hepatocellular carcinoma, frequently associated with genomic rearrangements. Next generation sequencing (NGS) is commonly used to study these integration sites and rearrangements; however, due to short read lengths, NGS is often unable to characterize large and complicated genomic rearrangements. To solve this problem, whole genome imaging was used to perform genome-wide detection of large structural variants (SVs) in DNA extracted from liver tumors, including characterization of HBV viral integration sites and nearby rearrangements. Ultra-high molecular weight DNA was extracted from liver tissue of four patients diagnosed with hepatocellular carcinoma. The DNA was fluorescently labeled at the motif CTTAAG, linearized, and imaged in nanochannel arrays using a Bionano Genomics Saphyr platform. Images of molecules were converted into digital single-molecule reads. 400X coverage of DNA molecules at least 150 kbp in length was collected for each sample. For three of the patients, somatic structural variants (SV) were identified by comparing SV calls and single molecule DNA reads of liver tumor resections against those of matching physiologically normal liver tissue. For the fourth patient, putative somatic SVs were identified by comparing SV calls against a database of 59,490 known variants from 57 physiologically normal individuals. Among the matched-pair samples, 511 large tumor-unique structural variants were identified. For the fourth sample, 619 putative somatic events were identified. HBV viral integration sites, which had previously been identified via NGS, and nearby SVs were characterized. Complex SVs were resolved, including translocation events with several loci. These findings demonstrate the utility of whole genome imaging for studying the relationship between viral integration and cancer.
Citation Format: Karl Hong, Camille Péneau, Quentin Bayard, Sandrine Imbeaud, Andy Pang, Alex Hastie, Eric Letouzé, Jessica Zucman-Rossi. Genome-wide structural variation analysis and characterization of Hepatitis B Virus integration sites in hepatocellular carcinomas using Bionano Genomics whole genome imaging [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 4897.
Abstract 492: A Novel QUATRAMER sustained injectable suspension for the intracellular delivery of Salinomycin, a stem cell inhibitor (HSB-1216), for the treatment of triple negative breast cancer
Authors: Kharbanda Surender M. , Mohammad Anees , Gupta Bhawana , Appajosyula Sireesh , Laumas Sandeep , Jain Jugnu , Kufe Donald , Singh Harpal 
Published: September 2020

Abstract
Triple-negative breast cancer (TNBC) accounts for approximately 15-20 % of all breast cancers, is an aggressive disease with a poor prognosis, and lacks targeted therapy. Recent studies suggest that cancer stem cells (CSCs) play an important role in TNBC progression and tumorigenesis and that targeting CSCs may be a promising, novel strategy for the treatment of this disease. Both CD44+/CD24- and CD44+/CD24 low CSCs are enriched in TNBCs and may contribute to chemotherapy resistance, emphasizing the need to target this population. In this regard, recent studies have shown that salinomycin (SAL) preferentially targets CSCs; however, the preclinical toxicity associated with this agent has limited its clinical development.In the current studies, we have generated novel biodegradable QUATRAMER polymeric nanoparticles comprised of a polyethylene glycol (PEG)-polypropylene glycol (PPG)-PEG modified polylactic acid (PLA)-tetra-block copolymer (SAL-NPs; HSB-1216) for the intracellular delivery of SAL. Treatment of human TNBC MDA-MB-231 cells with HSB-1216 was associated with significant cell death with an IC50 of around 2 uM. Similar results were obtained when other TNBC cell line SUM149 was treated with HSB-1216 (IC50 ~ 0.5 uM). Based on the characteristic formation of TNBC mammospheres in in vitro 3D culture conditions, the mammosphere formation assay has become an essential tool for quantifying CSC activity. Cultured MDA-MB-231 mammospheres were therefore exposed to different concentrations and durations of HSB-1216. Our results demonstrate dose-dependent inhibition of mammosphere formation in response to HSB-1216. Additionally, CD44+/CD24- enriched CSCs were isolated from a TNBC patient tumor biopsy, grown as 3D culture/mammospheres and then treated with HSB-1216. Interestingly, in contrast to Paclitaxel, treatment with HSB-1216 was associated with nearly complete inhibition of mammosphere formation. Taken together, these results demonstrate an effective method for sustained delivery of a potent stem cell inhibitor, SAL, and its potential for the treatment of TNBC.
Citation Format: Surender M. Kharbanda, Anees Mohammad, Bhawana Gupta, Sireesh Appajosyula, Sandeep Laumas, Jugnu Jain, Donald Kufe, Harpal Singh. A Novel QUATRAMER sustained injectable suspension for the intracellular delivery of Salinomycin, a stem cell inhibitor (HSB-1216), for the treatment of triple negative breast cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 492.
Abstract 4962: Tumor heterogeneity driven by cancer stem cell expressing POU5F1
Authors: Miyoshi Norikatsu , Fujino Shiki , Sasaki Masaru , Ogino Takayuki , Takahashi Hidekazu , Uemura Mamoru , Matsuda Chu , Mizushima Tsunekazu , Eguchi Hidetoshi , Doki Yuichiro 
Published: September 2020

Abstract
Background: The gene POU5F1, encoding the POU domain, class 5, is a transcription factor. and the expression is found in embryonic stem cells. In these pluripotent stem cells, POU5F1 gene controls self-renewal and differentiation, regulating the pluripotency and proliferation. Regarding the tumor heterogeneity and microenvironment, primary culture of cancer cells derived from the patient's tumor can provide important information of the “individual tumor,” representing the tumor heterogeneity. We focused on the gene expression and the relationship between colorectal cancer stem cells and the tumor heterogeneity, in the primary culture model.
Methods: Using POU5F1 promoter-containing sequence, POU5F1-EGFP-positive cells were established by the construct with lentiviral vector, and we examined their sub-populations. The capacity to form distant metastasis in vivo was examined using the primary culture models.
Results: We obtained clinical samples from surgically resected gastrointestinal cancers. They were mechanically and enzymatically digested and collected using customized filters. Obtained cells were cultured on a matrix-coated plate with chemically defined stem-cell culture medium. All these primary cultured cells grew and about 90% of them were successfully passaged. The morphology and gene expressions were similar to each parental clinical tumor. Using these primary tumors, POU5F1 expressing cells were examined. The POU5F1-EGFP-positive cells highly expressed stem cell-associated markers and they had self-renewal and differentiation abilities. POU5F1-high cells actively formed liver metastasis.
Conclusion: POU5F1-positive cells have the self-renewal and differentiation abilities as cancer stem cells. The positive cells produce tumor heterogeneity. POU5F1 contributes to the ability forming liver metastasis in CRC. Keywords: colorectal cancer, tumor heterogeneity, metastasis, POU5F1.
Citation Format: Norikatsu Miyoshi, Shiki Fujino, Masaru Sasaki, Takayuki Ogino, Hidekazu Takahashi, Mamoru Uemura, Chu Matsuda, Tsunekazu Mizushima, Hidetoshi Eguchi, Yuichiro Doki. Tumor heterogeneity driven by cancer stem cell expressing POU5F1 [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 4962.
Abstract 4986: Utilizing image analysis to characterize an 8-plex immunofluorescence immune checkpoint biomarker panel within the tumor tissue microenvironment
Authors: Bigley Alison L. , Sherry Lorcan A. , Stillie Nicole , Wood Douglas , Downing Sean 
Published: September 2020

Abstract
Multiplex staining and image analysis are being increasingly deployed for immuno-oncology (I/O) evaluations to investigate and understand the complexity of immune cell / tumor cell interactions in the tumor microenvironment (TME) and in discovering novel predictive biomarkers for targeted immunotherapy. Immune checkpoint inhibitor treatment, guided by immunohistochemically labelled tissue expression of PD-L1 and PD-1, have already been shown to improve outcomes, in the metastatic setting, for non-small cell lung carcinoma (NSCLC) and colorectal cancer (CRC) patients. The purpose of the current study was to phenotype and compare checkpoint and immune cell interactions within NSCLC and CRC tumor types. The study included samples from NSCLC, CRC, and normal tonsil tissues. Sections were stained using InSituPlex® multiplex immunofluorescence (mIF), for studying PD-L1/PD-1 checkpoint expression including immune cell markers for CD3, CD4, CD8, CD68, FoxP3, and pan-CK as an epithelial tumor indicator. Slides were scanned at 20X magnification on the ZEISS Axio Scan.Z1 platform, with individual .tiff format files being generated per marker. Image analysis was performed using the Visiopharm® Oncotopix® platform. Individual marker image layers were aligned, tumor/stroma regions of interest (ROI) classified, and cell formations detected. Quantification of markers was determined across the image layers to evaluate positive cell staining within both cancer indications. Quantitative image analysis data generated included total positive and negative cell counts per marker, per mm2 ROI. Co-localization analysis provided relevant immune cell phenotypes (T-cytotoxic, T-helper, T-regs, and macrophages) and immune cell functional status. Cell spatial analysis relationships were generated, including CD8+/PD-1− and CD8+/PD-1+ to CK+/PD-L1+ tumor cells. This study highlighted the benefits of utilizing an 8-plex staining protocol and detailed image analysis approach for the comprehensive assessment of the immune cell types and interactions within the TME. The ability to carry out multiparameter cellular analysis facilitates the delivery of key phenotypic data, thereby leading to greater understanding of tumor biology.
Citation Format: Alison L. Bigley, Lorcan A. Sherry, Nicole Stillie, Douglas Wood, Sean Downing. Utilizing image analysis to characterize an 8-plex immunofluorescence immune checkpoint biomarker panel within the tumor tissue microenvironment [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 4986.
Abstract 5000: YB-1 based oncolytic virotherapy in combination with small molecular inhibitors for treatment of refractory osteosarcoma
Authors: Middendorf Charlotte Friederike , Schober Sebastian Johannes , Kordass Corazón , Nawroth Roman , Burdach Stefan E. , Holm Per Sonne , Thiel Uwe 
Published: September 2020

Abstract
This in vitro study evaluates YB-1 based oncolytic virotherapy in combination with molecular target therapy as a novel therapeutic strategy for refractory osteosarcoma.
In vitro combination approaches include CDK4/6-, MDM2- and PARP-inhibitors. The treatment strategy was explored in four established osteosarcoma cell lines (143B, MG-63, SJSA, U2OS). Intracellular YB-1 expression was evaluated by immunofluorescence for oncolytic therapy with YB-1 selective adenovirus XVir-N-31. Efficacy of mono- and combination therapy is assessed using cell survival assays. The Chou Talalay method is used to determine synergistic effects between combinational components. Characterization of molecular pathways associated with oncolytic cytotoxicity is done using cell cycle analysis, western blotting, hexon titer test, sqPCR and ELISA.
We observe a potent preclinical anti-tumor effect using XVir-N-31 monotherapy on all tested osteosarcoma cell lines. However, most cell lines were resistant towards inhibitor monotherapy in clinically achievable concentrations. In contrast, all dual combinations resulted in significantly enhanced cytotoxicity. These results require reduced numbers of infectious viral particles and are observed at clinically implementable inhibitor concentrations. Increased oncolytic cytotoxicity is associated with changes of tumor cell cycle regulation due to inhibitor treatment and modulation of infectious viral particle formation.
In summary, we determine XVir-N-31 as a potent oncolytic agent for the treatment of refractory osteosarcoma. We provide a strong preclinical rationale for the combination of oncolytic adenovirus with molecular target therapy. A phase I clinical trial with XVir-N-31 in combination with molecular target therapy for refractory childhood sarcoma is planned.
Citation Format: Charlotte Friederike Middendorf, Sebastian Johannes Schober, Corazón Kordass, Roman Nawroth, Stefan E. Burdach, Per Sonne Holm, Uwe Thiel. YB-1 based oncolytic virotherapy in combination with small molecular inhibitors for treatment of refractory osteosarcoma [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 5000.
Abstract 5029: Targeting fatty acid oxidation to promote anoikis and inhibit ovarian cancer progression
Authors: Bitler Benjamin Guy , Sawyer Brandon , Qamar Lubna , Richer Jennifer K. , Behbakht Kian , Schlaepfer Isabel R. 
Published: September 2020

Abstract
Purpose: Epithelial-derived high-grade serous ovarian cancer (HGSOC) is the deadliest gynecologic malignancy and in the US accounts for over 14,000 deaths per year. Roughly 80% of patients are diagnosed with late-stage disease, which is defined by wide-spread cancer dissemination throughout the pelvic and peritoneal cavities. HGSOC dissemination is dependent on tumor cells acquiring the ability to resist anoikis (apoptosis triggered by the loss of attachment). Epithelial cell detachment from the underlying basement membrane or extracellular matrix leads to cellular stress, including nutrient-deprivation. Reports describe metabolic reprogramming that promotes fatty acid oxidation (FAO) potentially supports anoikis resistance.
Experimental Design: Examination of a panel of HGSOC cell lines cultured in adherent and suspension conditions. Evaluated anoikis by caspase 3/7 activity, cleaved caspase 3 immunofluorescence, and flow cytometry. Using the Seahorse Bioanalyzer examined mitochondria activity in suspension. Tested the role of exogenous free fatty acids in anoikis resistance and metabolism. In a patient-derived xenograft model, administered an FAO inhibitor and/or platinum-based chemotherapy.
Results: HGSOC cultured in suspension upregulated the FAO rate-limiting enzyme, Carnitine Palmitoyltransferase 1A (CPT1A). CPT1A is overexpressed in HGSOC and correlates with poor overall survival. The knockdown of CPT1A promoted anoikis. HGSOC cells in suspension culture have decreased oxygen consumption that is rescued by exogenous fatty acids. In a patient-derived xenograft of HGSOC, a CPT1A inhibitor, etomoxir, significantly inhibited tumor growth and reduced tumor distribution.
Conclusions: Targeting FAO in HGSOC to promote anoikis and attenuate dissemination is a potential approach to promote a more durable anti-tumor response and improve patient outcomes.
Citation Format: Benjamin Guy Bitler, Brandon Sawyer, Lubna Qamar, Jennifer K. Richer, Kian Behbakht, Isabel R. Schlaepfer. Targeting fatty acid oxidation to promote anoikis and inhibit ovarian 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 5029.
Abstract 5030: Vitamin D exhibits therapeutic anti-tumor and anti-angiogenic potential by reducing VEGF levels and altering TIMP/MMP system in breast cancer
Authors: Bajbouj Khuloud , Shafarin Jasmin , Sawan Ahmad , Shehada Ahmed , Elkhalifa Walaa Eldin 
Published: September 2020

Abstract
Background: Clinical and experimental observations suggest that Vitamin D deficiency associates with increased risk of breast cancer. Furthermore, studies concluded that Vitamin D precipitates in significant anti-neoplastic effects against breast, and inducing apoptosis and affecting angiogenesis in other types of cancer. However, the exact mechanism underlying this anti-angiogenic effect of Vitamin D is still elusive. This study aims to investigate the anti-cancer role of Vitamin D anti-cancer and its association with modulation of major factors involved in angiogenesis and metastasis in breast cancer cell lines.
Experimental methods: The hormonally active form of vitamin D, 1α,25-dihydroxyvitamin D3 (calcitriol), was used to evaluate anti-proliferative effect, inhibition of cell cycle progression and apoptosis induction in two breast cancer cell lines, MCF-7 and MDA-MB-231. Furthermore, impact of calcitriol on expression and activity of tissue inhibitors of metalloproteinases (TIMP), major groups of the matrix metalloproteinases (MMPs), vascular endothelial growth factor (VEGF), and tumor growth factor (TGF-β1) among others involved in tumor progression and angiogenesis were also examined.
Results and Discussions: Calcitriol treatment (10 µM) significantly inhibited cell proliferation in a timely dependent manner. Both cell lines showed G1 cell cycle arrest, decreased levels of the cell death inhibitor, survivin, and apoptosis induction in response to calcitriol treatment. Proteome Profiler array analysis revealed that calcitriol resulted in reducing the levels of major pro-angiogenesis regulators, especially VEGF, TGF-β1, Urokinase-type plasminogen activator (uPA), and Amphiregulin. Analysis of mRNA and proteins expression upon calcitriol exposure showed an increase of TIMP1, TIMP2 and a decrease in MMP 2, 3 and 9 levels. Finally, quantitative analysis using ELISA revealed that calcitriol treatment reduced MMP2 and MMP9 activities.
Conclusion: Our study demonstrates potential therapeutic property of calcitriol through inhibiting of pro-angiogenetic markers in breast cancer.
Citation Format: Khuloud Bajbouj, Jasmin Shafarin, Ahmad Sawan, Ahmed Shehada, Walaa Eldin Elkhalifa. Vitamin D exhibits therapeutic anti-tumor and anti-angiogenic potential by reducing VEGF levels and altering TIMP/MMP system in breast cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5030.
Abstract 5050: Novel TNFR2 humanized mouse model for human TNFR2 antibody evaluation
Authors: Guo Yanan , Li Yanan , Zhou Xiaofei , Su Youhong , Lin Qingcong 
Published: September 2020

Abstract
In recent years, immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment. Tumor necrosis factor receptor 2 (TNFR2), also known as tumor necrosis factor receptor superfamily member 1B (TNFRSF1B), is a transmembrane receptor that has been linked into immune modulation and tissue regeneration. TNFR2 is mainly expressed on the surface of a subset of potent regulatory T cells (Tregs) and promote the proliferation of Tregs through nuclear factor kappa B (NF-κB). Anti-TNFR2 antibodies have been developed to inhibit NF-κB driven growth and have revived excitement for the use of anti-TNFR2 antibodies in the clinic.
To investigate the role of TNFR2, Biocytogen generated TNFR2 humanized mouse for both in vitro function validation of signaling pathway and in vivo efficacy evaluation of TNFR2 antibodies. In this model, the exon 2~6 of mouse Tnfr2 gene which encode the extracellular was replaced by human TNFR2 counterparts. Human TNFR2 is detectable on the Tregs in spleen and the TNFR2 antibodies bind well to the splenocytes of the TNFR2 humanized mice. Basal leukocyte subpopulations of TNFR2 humanized mice are comparable to that of wild-type mice, including T/B cells, NK cells, DC, granulocytes and monocytes/macrophages. Anti-human TNFR2 antibodies can repress the growth of colon cancer cells engrafted on TNFR2 humanized mice. The TNFα/TNFR2 signaling pathway is under validation on TNFR2 humanized mice and TNFα/TNFR2 double humanized mice due to the uncertain cross-reactivity between mouse and human TNFα/TNFR2.
Taken together, TNFR2 humanized mice is a useful tool for in vivo efficacy evaluation of human TNFR2 antibodies that can be advanced to human clinical trials.
Citation Format: Yanan Guo, Yanan Li, Xiaofei Zhou, Youhong Su, Qingcong Lin. Novel TNFR2 humanized mouse model for human TNFR2 antibody evaluation [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 5050.