bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract LB060: Circulating tumor cells in desmoid tumors
Authors: Braun Alexcia Camila , Campos Fernando , Abdallah Emne Ali , Ruano Anna Paula , Tariki Milena , Pinto Fabio , de Mello Celso Abdon , Martins Vilma Regina , Chinen Ludmilla Thome 
Published: July 2021

Abstract
Introduction: Desmoid tumor (DT) is a rare neoplasm with high local recurrence rates. CTNNB1 mutations are found in most sporadic cases and are located in exon 3, usually in codons 41 or 45 (p.T41A, p.S45F and p.S45P). Circulating tumor cells (CTCs) isolated from the peripheral blood of patients with sarcomas and other neoplasms can be early biomarkers of tumor invasion and dissemination. Moreover, CTCs can also re-colonize their tumors of origin through a process of “tumor self-seeding.” Objectives: To identify CTCs in the peripheral blood of patients with DT; to evaluate their expressions of β- catenin and vimentin proteins. Materials and methods: We conducted a prospective study of patients with initially diagnosed and relapsed DT with measurable disease. Blood samples from each patient were processed and filtered by ISET® (Rarecells, France) for the isolation and quantification of CTCs. The expressions of β -catenin and vimentin in CTCs were analyzed by immunocytochemistry (ICC). Results: A total of 18 patients were included, and all had detectable CTCs. We found a concordance of β-catenin expression in CTCs and in primary tumors in 42.85% of cases by using ICC and immunohistochemistry respectively. Conclusions: Our study identified a high prevalence of CTCs in DT patients. Concordance of β-catenin expression between primary tumor and CTCs bring new perspectives to assess the dynamics of CTCs in the blood microenvironment, opening new avenues for studying the biology and behavior of DT. In addition, these results open the possibility of using CTCs to predict DT dynamics at the time of progression and during treatment. Further studies with larger sample sizes are needed to validate our findings.
Citation Format: Alexcia Camila Braun, Fernando Campos, Emne Ali Abdallah, Anna Paula Ruano, Milena Tariki, Fabio Pinto, Celso Abdon de Mello, Vilma Regina Martins, Ludmilla Thome Chinen. Circulating tumor cells in desmoid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB060.
Abstract LB065: Prostate cancer molecular immunophenotypes in biopsies with high vs average radiation sensitivity as predicted by post-operative radiation therapy outcomes (PORTOS) scores
Authors: Gaston Sandra M. , Punnen Sanoj , Kryvenko Oleksandr , Pollack Alan , Davicioni Elai , Liu Seagle , Stoyanova Radka 
Published: July 2021

Abstract
Background: The combination of radiation therapy and immunotherapy has emerged as an exciting field of research with the potential for significant clinical benefit. Using pre-treatment prostate biopsies from two clinical trials we explored the hypothesis that a validated gene expression signature of postoperative radiation therapy outcome score (PORTOS) is associated with differences in tumor molecular immunophenotype. In this study, we compared prostate tumors with high vs average PORTOS scores for expression of 32 molecular immunophenoscores that reflect cancer antigen profiles and the cellular composition of tumor infiltrating lymphocytes. Methods: Gene expression profiles were obtained from microdissected tumor tissue from 242 treatment naïve-prostate biopsy cores obtained from 92 patients enrolled in the University of Miami MAST (NCT02242773) and BLaStM (NCT02307058) clinical trials. For each biopsy the PORTOS score (PMID: 27743920) and 32 tumor molecular immunophenoscores (PMID: 28052254) were determined from Affymetrix Human Exon 1.0 ST microarray data using published methods. Results: 14% of the biopsy cores were predicted by the PORTOS signature to be more responsive to radiation therapy. Compared to the cores with average PORTOS scores, the “high PORTOS” biopsies showed a 2 fold or greater level of the tumor immunoactivation markers Act CD4, Act CD8, EC, HLA DPA1 and Tem CD8 and a 2 fold or lower level of the tumor immunosuppression markers MDSC, SC, TIM3 and T reg (Mann-Whitney P value of &lt;0.0001 for all nine comparisons of medians). Discussion: Preliminary studies suggest that prostate cancers with PORTOS scores that predict greater sensitivity to radiation therapy also have immunophenotype profiles consistent with a higher level of overall immunogenicity.
Citation Format: Sandra M. Gaston, Sanoj Punnen, Oleksandr Kryvenko, Alan Pollack, Elai Davicioni, Seagle Liu, Radka Stoyanova. Prostate cancer molecular immunophenotypes in biopsies with high vs average radiation sensitivity as predicted by post-operative radiation therapy outcomes (PORTOS) scores [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB065.
Abstract LB082: Prostate cancer incidence and mortality in the United States, 2000-2016
Authors: Koko Michael Rutalira , Aranmolate Rasaki , Shah Raza Z. , Mutamba Glodi 
Published: July 2021

Abstract
Background/Purpose
Prostate cancer (PC) is the second most common and deadly cancer among men in the United States. In general, incidence rate of prostate cancer has declined while mortality rate has increased over the past 15 years. The purpose of this study is to assess the incidence and mortality rates of this cancer according to race/ethnicity from 2000-2016.
Methods
We obtained data from the Surveillance, Epidemiology and End Results (SEER) 18 program to calculate incidence and mortality rates by race/ethnicity from 2000 to 2016. The Annual Percent Change (APC) was also obtained for incidence and mortality rates by race/ethnicity.
Results
From 2000-2016, the overall incidence rate has decreased significantly from 77.4 to 49.1 per 100,000 (APC = -3.1). Asian and Pacific Islander had the highest decline in incidence rate from 44.4 to 23.4 per 100,000 whereas African-American had the lowest decline from 113.3 to 72.4 per 100,000 (APC -4.4 vs -2.9 respectively). Conversely, the death rate has increased substantially, particularly among White and Black (APC = 8.6 vs 6.6). However, African-Americans still have a disproportionate mortality rate compared to White (46.5 vs 28.8 per 100,000).
Conclusion
African-Americans are still suffering disproportionately from the PC. There is a need to implement public health interventions to improve PC screening among African-Americans, and examine additional factors that may contribute to the burden of this cancer among African-Americans.
Citation Format: Michael Rutalira Koko, Rasaki Aranmolate, Raza Z. Shah, Glodi Mutamba. Prostate cancer incidence and mortality in the United States, 2000-2016 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB082.
Abstract LB086: Methylation-derived neutrophil-to-lymphocyte ratio and lung cancer risk and survival
Authors: Zhao Naisi , Ruan Mengyuan , Koestler Devin , Lu Jiayun , Marsit Carmen , Kelsey Karl , Platz Elizabeth , Michaud Dominique S. 
Published: July 2021

Abstract
The neutrophil-to-lymphocyte ratio (NLR) is a biomarker of systemic inflammation and can be estimated using DNA methylation data as methylation-derived NLR (mdNLR). We examined associations between mdNLR and lung cancer risk in a nested case-control study, and among the cases, lung cancer survival, using pre-diagnostic blood samples of cases (median of 14 years before diagnosis) and controls in the CLUE I/II cohorts. The final analytic dataset included 208 pairs of lung cancer cases and controls matched on age, sex, and smoking intensity. We computed the mdNLR for each sample based on immune cell-proportion estimates obtained using established reference-based deconvolution methods. Using conditional logistic regression (to take into account matching factors), and further adjusting for BMI, batch effects, and a smoking-based methylation score, we observed a 47% increased risk of non-small cell lung cancer (NSCLC) for one standard deviation increase in mdNLR (n = 150 pairs; OR: 1.47 [1.08, 2.02]). To estimate association between mdNLR and lung cancer survival, we used Cox proportional-hazards models, adjusting age, sex, smoking status, smoking methylation score, BMI, batch effect, and stage. We observed a 27% increased risk of dying from lung cancer for one standard deviation increase in mdNLR (n = 145 deaths in 205 cases; HR: 1.27 [1.08, 1.50]). A 50% increased risk of dying from lung cancer for one standard deviation increase in mdNLR was observed for NSCLC cases (n = 103 deaths in 149 cases; HR: 1.50 [1.19, 1.89]). A better understanding of inflammation-associated biomarkers in lung cancer development could provide insight into critical pathways that may help identify new markers of early disease and survival.
Citation Format: Naisi Zhao, Mengyuan Ruan, Devin Koestler, Jiayun Lu, Carmen Marsit, Karl Kelsey, Elizabeth Platz, Dominique S. Michaud. Methylation-derived neutrophil-to-lymphocyte ratio and lung cancer risk and survival [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB086.
Abstract LB098: Vulnerability of MTAP-deleted nasopharyngeal carcinoma to MAT2A inhibition
Authors: Chan Yuk Yu , Bruce Jeff P. , Lui Vivian W.Y. , Chung Grace T. Y. , Tsao Sai-Wah , To Ka-Fai , Pugh Trevor J. , Lo Kwok-Wai 
Published: July 2021

Abstract
Nasopharyngeal carcinoma (NPC) is an EBV-associated cancer prevalent in Southern China and Southeast Asia. We have generated a comprehensive genomic profile of NPC using whole-genome sequencing (WGS) and established a catalogue of somatic alterations of this EBV-associated cancer. In addition to the significantly mutated genes reported in previous WES studies, our WGS study revealed recurrent structural variants (SVs) and copy number variants (CNVs) driving key oncogenic pathways, including cell cycle, NF-kappaB and TGF-beta signaling. While immediately druggable gene aberrations (e.g. PIK3CA mutations and FGFR3-TACC3 fusions) are found in only ~3-5% of NPC, a synthetic lethality-based target, homozygous deletion of MTAP defined by fine-mapping of CDKN2A/CDKN2B deletion breakpoints at chromosome 9p21.3 was frequently detected (34%). Notably, the study has also revealed mutual exclusivity among tumors with MTAP deletion and TP53 alterations (p=0.022). Loss of MTAP has further been validated in a cohort of advanced and recurrent tumors (16/50, 32%) by FISH analysis and immunohistochemistry staining. The high prevalence and clonal nature of MTAP deletion in NPC implicate synthetic lethal targeting of MTAP-deleted tumors as a potential precision treatment for NPC patients. Using a CRISPR-based MTAP-knockout cell line and MTAP-deleted patient derived xenograft (PDX), we revealed that MAT2A and PRMT5 inhibition selectively suppressed growth of MTAP-deleted NPC. Treatment with MAT2A inhibitor, FIADS-5, led to depleted PRMT5 activity and reduced symmetric arginine methylation (SAMe) in these in vitro and in vivo NPC models. In addition to selective growth inhibition, MAT2A inhibition also targeted various unique oncogenic properties in NPC. The FIADS-5 treatment was shown to induce TP53 and BAX expression, cellular differentiation and keratinization in these MTAP-deleted NPC. Our findings demonstrated the translational potential of targeting MTAP-deletion in this EBV-associated epithelial cancer.
Citation Format: Yuk Yu Chan, Jeff P. Bruce, Vivian W.Y. Lui, Grace T. Y. Chung, Sai-Wah Tsao, Ka-Fai To, Trevor J. Pugh, Kwok-Wai Lo. Vulnerability of MTAP-deleted nasopharyngeal carcinoma to MAT2A inhibition [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB098.
Abstract LB106: The EGF domains of MUC4 oncomucin interact with ErbB2 and mediate tumorigenic activity of cancer cells represent new potential therapeutic targets
Authors: STOUP Nicolas , LIBERELLE Maxime , SCHULZ Céline , VASSEUR Romain , MAGNEZ Romain , THURU Xavier , MELNYK Patricia , RENAULT Nicolas , JONCKHEERE Nicolas , LEBEGUE Nicolas , VAN SEUNINGEN Isabelle 
Published: July 2021

Abstract
The MUC4 mucin and its membrane partner ErbB2 form an oncogenic complex at the surface of epithelial cancer cells that promotes tumor progression. They directly physically interact via an extracellular region of MUC4 encompassing three EGF domains opening the route to therapeutic targeting of ErbB2 over-expressing cancers in which MUC4-ErbB2 is present. However, before small inhibitory molecules may be designed, it is mandatory (i) to decipher at the molecular level which amino acid regions are involved in the interaction and (ii) show that they mediate cancer cell tumorigenicity. By using in vitro (2D cell culture, Micro Scale Thermophoresis, PLA assay, Co-IP, GST pull down, Molecular Dynamics simulations) and in vivo (xenograft model of pancreatic cancer) approaches, we show that the EGF1 domain of MUC4 is central both in the interaction with ErbB2 and in the activation of cell proliferation and migration and tumor growth via activation of key oncogenic pathways (Src, Ras, p70S6K/AKT/mTOR, β-catenin, FAK). Finally, we have identified hotspots of interaction paving the way to the design of therapeutic inhibitory molecules targeting the EGF domains of MUC4 which may represent a new alternative strategy to overcome ErbB2 therapeutic failure in cancer.
Citation Format: Nicolas STOUP, Maxime LIBERELLE, Céline SCHULZ, Romain VASSEUR, Romain MAGNEZ, Xavier THURU, Patricia MELNYK, Nicolas RENAULT, Nicolas JONCKHEERE, Nicolas LEBEGUE, Isabelle VAN SEUNINGEN. The EGF domains of MUC4 oncomucin interact with ErbB2 and mediate tumorigenic activity of cancer cells represent new potential therapeutic targets [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB106.
Abstract LB113: Regulation of PARP-1 expression in mammary tumor cell lines after treatment with olaparib
Authors: Moschetta-Pinheiro Marina Gobbe , Colombo Jucimara , de Souza Tuckumantel Murilo , Rebolho Gabriela Karam , Zuccari Debora Aparecida 
Published: July 2021

Abstract
Introduction: Breast cancer is the most common tumor type among women and has a high mortality rate, which is associated with late detection of the disease and treatment failure due to the acquisition of resistance to protocol treatments. It is known that a variety of antitumor drugs are capable of inducing chemoresistance by activating DNA repair pathways. Among these, the PARPs are involved in the recognition and repair of simple-strand breaks. As a consequence, new drugs such as PARP inhibitors (olaparib), are being investigated as potential therapeutic targets in cancer, as an alternative to evade the resistance of tumor cells to chemotherapeutic agents, such as those in the class of platinum salts. In this context, the aim of this study was to evaluate the PARP expression after olaparib tratament with in mammary tumor cell lines. Materials and Methods: Mammary tumor cell lines MDA-MB-468 and CF41 was cultured in DMEM high glucose culture medium, at 37°C in 5% CO2. Cell viability was measured by MTT assay after treatment with different concentrations of carboplatin. Once stablished the concentration of 10µM for carboplatin and 10µM of olaparib, the protein and gene expression of PARP-1 were detected by immunofluorescence and real time PCR, respectively. Results: There was a significantly decrease of cell viability after treatment with different concentrations of carboplatin in 24 hours. Both PARP-1 protein and gene expression significantly decreased after treatment with carboplatin and olaparib. In some cases, the treatment action was potentiated when performed in combination. Conclusion: Our results suggest the efficacy of olaparib in controlling the mechanism of DNA repair activated by PARPs in human and canine breast cancer cells.
Citation Format: Marina Gobbe Moschetta-Pinheiro, Jucimara Colombo, Murilo de Souza Tuckumantel, Gabriela Karam Rebolho, Debora Aparecida Zuccari. Regulation of PARP-1 expression in mammary tumor cell lines after treatment with olaparib [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB113.
Abstract LB133: Targetting IL-6/gp130 signalling axis attenuates acquired drug resistance in medulloblastoma
Authors: Sreenivasan Lakshana , Leclair Pascal , Lim Chinten James 
Published: July 2021

Abstract
Medulloblastoma (MB) is the most common pediatric brain tumour comprising of four distinct molecular subgroups exhibiting high level of intertumoural heterogeneity. The standard multimodal treatment yields a survival rate of 70% but the aggressive treatment affects the long-term sequelae of MB patients. The tumour microenvironment (TME) is a regulator of cancer progression and affects therapeutic efficacy in primary and metastatic brain malignancies. Mechanistic insights into the tumor-promoting role of the individual components of the brain TME will aid in identifying key survival pathways and design of potential therapeutics to combat drug resistance and pathogenesis of the disease. We hypothesize that tumor associated macrophages (TAMs) in the brain TME facilitate drug resistance via the IL-6/STAT3 signalling axis in MB. To understand the role of paracrine signaling resulting from TAMs, a co-culture system was used to evaluate the expression of pSTAT3 and correlated with drug sensitivity and/or resistance in Med8A cell line. When co-cultured with HMC3, a human microglia cell line, the chemosensitive Med8A-S cells exhibited enhanced pSTAT3 expression and acquired drug resistance. Interestingly, Med8A cells lacking expression of IL-6 receptor (IL6R-/-) also exhibited high pSTAT3 levels and drug resistance; suggesting that HMC3 may release soluble factors in addition to IL-6 sufficient to drive chemoresistance in Med8A variants. To assess this, we conditioned cells with stimulatory cytokines belonging to the IL-6 family. We found that oncostatin M (OSM), interleukin-11 (IL-11) and leukemia inhibitory factor (LIF) induced drug resistance and enhanced pSTAT3 levels in IL6R-/- cells. Receptors of the IL-6 family share a common signal transducing beta subunit, glycoprotein (gp130) that transduces the signal intracellularly and phosphorylates janus activated kinases (JAKs) and subsequently STAT3. Our results suggest that paracrine proinflammatory cytokines found in the TME can promote MB drug resistance by signalling through a common signal transducer gp130, hence targeting any one cytokine receptor of the IL-6 family of cytokines may not sufficiently abrogate acquired drug resistance. Currently, we are evaluating the efficacy of agents that target common downstream elements of the IL-6/STAT3 signalling axis, including gp130, JAKs and STAT3, as a potentially improved therapeutic strategy to circumvent acquired drug resistance in medulloblastoma.
Citation Format: Lakshana Sreenivasan, Pascal Leclair, Chinten James Lim. Targetting IL-6/gp130 signalling axis attenuates acquired drug resistance in medulloblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB133.
Abstract LB143: BNZ-2, a dual specific IL15/IL21 inhibitor, rescues humanized NOG-IL15 transgenic mice from intestinal acute graft versus host disease without disrupting NK and CD8 T cell engraftment
Authors: Kipp Kevin R. , Doerr Nick , Al-Mawsawi Laith Q. , Kim Woo Jae , Giovannone Adrian J. , Azimi Nazli 
Published: July 2021

Abstract
Advances in adoptive transfer immunotherapy have found beneficial effects for Interleukin-15 (IL-15) in the graft versus tumor (GvT) activity of NK and cytotoxic T cells. However, the benefits of this activity must be weighed against the increased risk of acute graft versus host disease (GvHD) in patients. We propose that BNZ-2, a peptide antagonist of IL-15 and IL-21 signaling, as a therapeutic option for GvHD that may relieve intestinal pathologies while retaining adoptive transfer activity. As a novel model of intestinal inflammatory disease, we have found that humanization with peripheral blood mononuclear cells (PBMCs) of NOG mice with transgenic expression of human IL-15 (NOG-IL15) consistently catalyzes the onset of intestinal GvHD within twenty days of engraftment. To investigate whether BNZ-2 can inhibit IL-15-catalized intestinal GvHD we treated NOG-IL15 mice and assessed the degree of intestinal GvHD and the immunophenotype of engrafted cells following twenty days of humanization with four million unmanipulated PBMCs. BNZ-2 treatment inhibited with equal efficacy to anti-IL-15 the localization of immune cells to the intestinal lamina propria protecting the tissue from inflammation-induced loss of tissue integrity. However, BNZ-2 treatment retained the systemic engraftment of the blood and spleen, including NK and CD8 cytotoxic T-cells. These data support BNZ-2 as a therapeutic candidate for GvHD treatment, describe a new model of intestinal GvHD, and suggest that a therapeutic window exists that separates intestinal GvHD pathologies from the benefits of adoptive cell transfer.
Citation Format: Kevin R. Kipp, Nick Doerr, Laith Q. Al-Mawsawi, Woo Jae Kim, Adrian J. Giovannone, Nazli Azimi. BNZ-2, a dual specific IL15/IL21 inhibitor, rescues humanized NOG-IL15 transgenic mice from intestinal acute graft versus host disease without disrupting NK and CD8 T cell engraftment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB143.