tbuckley/cabot-search huggingface dataset:
Abstract 362: The regulation of SOX7 and its tumor suppressive role in oral squamous cell carcinoma
Authors: Chi-Hyun Ahn, Kyoung Ok Hong, Ji-Ae Shin, Seong-Doo Hong, Sung-Dae Cho
Journal: Cancer Research (2020)

Abstract SRY-related HMG-box 7(SOX7), a transcription factor belonging to the SOX family, has been reported to be down-regulated in some types of cancers. However, its biologic role in oral squamous cell carcinoma (OSCC) remains unknown. We found expression of SOX7 protein was decreased in OSCC tissues compared with normal oral mucosa. SOX7 expression in patients with OSCC was inversely associated with positive lymph node metastasis, advanced TNM stage, and poor prognosis. These results were in accordance with data obtained from our in vitro experiments on the OSCC cell lines. Moreover, ectopic expression of SOX7 suppressed cell proliferation, migration, and invasion in HSC-4 and SCC-9 cells. Importantly, we discovered that SOX7 expression likely inhibited vasculogenic mimicry formation associated with clinically poor outcome and impaired expression of VE-cadherin in OSCC cell lines as well as lung cancer and breast cancer cells. Our findings suggest that SOX7 could be a potential marker for predicting the prognosis of patients with OSCC and plays an important role as a tumor suppressor in oral tumorigenesis and progression. This work was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT, and Future Planning [2017R1D1A1B03029317, 2018R1D1A1B07043080, and 2019R1A2C1085896]. Citation Format: Chi-Hyun Ahn, Kyoung Ok Hong, Ji-Ae Shin, Seong-Doo Hong, Sung-Dae Cho. The regulation of SOX7 and its tumor suppressive role in oral squamous cell carcinoma [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 362.
We need better evidence on non-drug interventions for covid-19
Authors: Margaret McCartney
Journal: BMJ (2020)

We need better evidence on non-drug interventions for covid-19Non-drug interventions should be based on evidence.We need to generate this to inform the covid-19 and future pandemics, argues Margaret McCartney Margaret McCartney GP partnerAlmost 1300 controlled trials have been registered for drug interventions for covid-19. 1Among them have been large, well powered, international trials that have assessed the effectiveness of treatments such as dexamethasone and hydroxychloroquine.But why have non-drug interventions not been subject to the same interrogation?The BESSI Collaboration (Behavioural, Environmental, Social, and Systems Interventions (for pandemic preparedness)) is currently being developed.But so far only 10 controlled trials of non-drug interventions have been registered, with three reported.
Abstract 4667: Associations between daily aspirin use and cancer risk across strata of major cancer risk factors in two large U.S. cohorts
Authors: Lauren M. Hurwitz, Kara A. Michels, Michael B. Cook, Ruth M. Pfeiffer, Britton Trabert
Journal: Cancer Research (2020)

Abstract Purpose: Daily low-dose aspirin is recommended for certain individuals for prevention of cardiovascular disease and colorectal cancer. However, there are known risks associated with aspirin use. Identifying subgroups of individuals most likely to benefit from aspirin for cancer prevention would help to tailor risk-benefit calculations to maximize benefits and minimize risks. We investigated whether associations between daily aspirin use and risk of several cancers vary by other cancer risk factors, including age, body mass index (BMI), smoking status, physical inactivity, and family history of cancer. Methods: We pooled 423,495 individuals from two prospective, U.S.-based studies: the NIH-AARP Diet and Health Study (1995-2011), a population-based cohort study, and the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (1993-2009), a multicenter randomized controlled trial. Daily aspirin use was self-reported at baseline and defined as use ≥5 days/week. Our main outcome measures were incident colorectal, ovarian, breast, endometrial, and aggressive prostate cancers. We used multivariable Cox proportional hazards regression to examine associations between daily aspirin use and risk of each cancer, overall and across strata of risk factors. Results: Compared with non-use and non-daily use, daily aspirin use was associated with a 15% reduction in colorectal cancer risk (hazard ratio [HR]: 0.85, 95% confidence interval [CI]: 0.80-0.89). Risk reductions were generally consistent across strata of other risk factors but attenuated with increasing BMI (p-interaction=0.16). For ovarian cancer, there was no significant association overall (HR: 0.93, 95% CI: 0.80-1.08) but a reduced risk among obese women (HR: 0.73, 95% CI: 0.52-0.98, p-interaction=0.12). We observed suggestive modest risk reductions for breast (HR: 0.96, 95% CI: 0.91-1.00) and aggressive prostate (HR: 0.95, 95% CI: 0.90-1.00) cancer and a null association for endometrial cancer (HR: 0.96, 95% CI: 0.86-1.07), with no strong effect modification observed. Conclusions: Daily aspirin use was associated with reduced colorectal cancer risk across strata of cancer risk factors. The magnitude of the benefit varied by BMI for colorectal cancer and was restricted to obese women for ovarian cancer. The potential modifying effect of BMI warrants further investigation and may need to be considered in risk-benefit calculations for aspirin use. Citation Format: Lauren M. Hurwitz, Kara A. Michels, Michael B. Cook, Ruth M. Pfeiffer, Britton Trabert. Associations between daily aspirin use and cancer risk across strata of major cancer risk factors in two large U.S. cohorts [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 4667.
Abstract 6209: Monocytes phagocytose neutrophil extracellular traps (NETs) and differentiate into pro-inflammatory macrophages
Authors: Akira Saito, Hideyuki Ozawa, Kazuya Takahashi, Yuki Kimura, Mineyuki Tojo, Yuko Kumagai, Rihito Kanamaru, Hidenori Tsukui, Naohiro Sata, Joji Kitayama
Journal: Cancer Research (2020)

Abstract Background: Macrophages are multipurpose phagocytes with various functions. Neutrophil extracellular traps (NETs) are web-like structures ensnare microbes which were composed of dsDNA, histones, and antimicrobial peptides. NETs are generally degraded by DNAse and macrophages, however, it is unknown how the degradation of NETs affects the local immune response thereafter. Here, we investigated the interaction between NETs and peripheral blood monocytes (PBMo). Method: 5 × 105 Polymorphonuclear leukocytes(PMNs), PMNs irradiated with UV for 15 minutes (UV-PMN) and PMNs stimulated by PMA for 15min and extensively washed (PMA-PMN) were placed on 6 well plate and cultured for 2 hours and NETs formation was visualized by SYTOX green. Peripheral blood was obtained from healthy volunteers and CD14+ PBMo were purified by positive selection using the magnetic cell separation system. The PBMo were co-cultured with those PMNs at 37°C in 5% CO2 conditions for 3 days. The differentiation of macrophage was evaluated by the expression of M1/M2 markers by flowcytometry. Cytokine production was evaluated using the Cytokine Array system. The macrophages were co-cultured with autologous T cells stimulated with anti-CD3 mAb and the effect on T cell proliferation was evaluated with CFSE dilution assay. Results: PMA-PMN, but not PMN or UV-PMN, produced massive SYTOX(+) NETs within 2 hours. Co-culture of the NETs with PBMo stained with PKH26 showed NETs are phagocytosed by monocytes within 24 hours. PBMo co-cultured with PMA-PMN showed significantly enhanced expression of CD86, and reduced expression of CD163 as compared to those co-cultured with PMNs or UV-PMN. However, the expression of CD86 was suppressed if PMA-PMN were pretreated with 100 u/ml DNase I. The supernatant of the co-culture with PMA-PMN showed markedly increased levels of IL-1β and TNF-α. PBMo co-cultured with PMA-PMN strongly promote the proliferation of autologous T cells. However, the enhanced T cell growth were significantly suppressed by the pretreatment of NETs with DNase I. Conclusion: Monocytes appear to differentiate to proinflammatory macrophages after the phagocytosis of NETs. In tumor-bearing host, NETs are known to be increased in circulating blood, which may promote tumor associated inflammatory process. Citation Format: Akira Saito, Hideyuki Ozawa, Kazuya Takahashi, Yuki Kimura, Mineyuki Tojo, Yuko Kumagai, Rihito Kanamaru, Hidenori Tsukui, Naohiro Sata, Joji Kitayama. Monocytes phagocytose neutrophil extracellular traps (NETs) and differentiate into pro-inflammatory macrophages [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 6209.
Abstract 2931: VGF as a theranostic marker in neuroendocrine lung cancer
Authors: Li-Hao Yang, Chia-Cherng Yu, Yu-Ting Chou
Journal: Cancer Research (2020)

Abstract Activating EGFR mutations are predictive markers for response in lung cancer patients under the treatment of EGFR-tyrosine kinase inhibitors (TKIs), whereas acquired resistance to EGFR-TKIs inevitably occurs in patients. Neuroendocrine transformation is one of the mechanisms behind the development of acquired resistance to EGFR-TKIs. In this study, we report that VGF, a secreted factor highly expressed in neurons and neuroendocrine tissues, is a potential theranostic marker in neuroendocrine lung tumors. Gene expression profiling analysis revealed that VGF levels were elevated during the differentiation of neuronal stem cells to neurons with surged H3K27ac modification at the VGF locus. We observed that VGF was highly expressed in lung neuroendocrine cancer cells. Moreover, VGF expression was low in lung adenocarcinoma but was enriched during EGFR-TKI selection. Correlation analysis showed that VGF was positively associated with chromogranin A, chromogranin B, and synaptophysin expression in lung tumors. ChIP-qPCR assays showed that the signal of H3K27ac modification at the VGF locus was increased in EGFR-TKI resistant cells compared to their sensitive counterparts. Clonogenic analysis and annexin-V staining assays revealed that VGF silencing attenuated cellular grown with increased apoptosis in neuroendocrine lung cancer cells as well as in EGFR-TKI resistant cells, indicating the potential of VGF as a therapeutic target. Kaplan-Meier analysis showed that high VGF expression predicted poor survival outcome in patients with lung tumors. Our findings provide an insight into the oncogenic role of VGF and suggest the potential of VGF as a theranostic for lung cancer. Citation Format: Li-Hao Yang, Chia-Cherng Yu, Yu-Ting Chou. VGF as a theranostic marker in neuroendocrine lung 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 2931.
SAT0082 FRAX AND DAS IN MOROCCAN RHEUMATOID ARTHRITIS PATIENTS
Authors: H. Azzouzi, O. Lamkhanat, I. Linda
Journal: Annals of the Rheumatic Diseases (2020)

Background: Rheumatoid Arthritis (RA) is one of the risk factors for the calculation of the 10 years fracture probability assessed by the FRAX tool. Objectives: The aim was to study the association of disease activity and the 10 year fracture risk probability by the FRAX tool in our RA patients and their impact on fracture prevalence. Methods: Cross-sectional study of the association FRAX and disease activity score (DAS 28 CRP) was designed. Patients with RA were included. Mean DAS was calculated for each patient adjusted on his follow-up duration. Data about patients (demographic, disease characteristics and fracture assessment) were collected. The 10 year fracture risk probability for major osteoporotic fracture was calculated with and without BMD (bone mineral density) using the FRAX tool for Morocco. Descriptive analysis and regressions were performed with SPSS.20. p&lt;0.05 was considered significant. Results: One hundred and ninety nine RA patients were included with mean age of 55.5±12 years. Women represented 91% and 40.1% had osteoporosis. Remission was observed in 86.4% with 95.5% taking methotrexate. 17.1% had vertebral fractures. FRAX and DAS were associated (p=0.03), and both explained vertebral fracture (VF) prevalence. When adjusted on disease parameters, FRAX with and without BMD explained the vertebral prevalence (p=0.02, OR=1.09[1.01-1.19]). However, age remains the only predictor of VF when adjusted on osteoporosis factors (DAS28CRP, menopause, BMI, smoking, diabetes, gender, steroid use, HAQ) and FRAX BMD. Conclusion: Persistent disease activity was associated to high 10 year fracture risk probability calculated by the FRAX tool in RA. Disclosure of Interests: None declared
Abstract 394: LXR agonist N,N-dimethyl-3-β-hydroxy-cholenamide, DMHCA, reduces ErbB2-dependent tumorigenesis and immune tolerance in a conditional model of mammary fibrosis
Authors: Robert I. Glazer, Gao Sheng, Hongyan Yuan, Suman Ranjit, Jin Lu, Xun Lu, Moshe Levi
Journal: Cancer Research (2020)

Abstract Background: One of the central challenges for cancer therapy is the identification of factors in the tumor microenvironment that increase tumor progression and prevent the immune system from eradicating the tumor. One such factor associated with breast cancer is stromal fibrosis, a histopathologic criterion for invasive cancer and poor survival. Fibrosis is caused by inflammatory factors and remodeling of the extracellular matrix, which results in excessive collagen deposition and an immune tolerant environment. Experimental Procedures: We developed a novel transgenic model representative of HER2/ErbB2+ breast cancer, termed NeuT/ATTAC, in which partial ablation of mammary fat resulted in its replacement with fibrotic tissue. NeuT/ATTAC mice were administered a diet supplemented with 0.04% DMHCA, a desmosterol-like pan agonist of the liver X receptor (LXR). Collagen deposition resulting from fibrosis was assessed by second harmonic generation (SHG) fluorescence microscopy and histological staining, immune cell subsets were analyzed by fluorescence-activated cell sorting and biomarkers of fibrosis, proliferation and immune tolerance were determined by IHC. Findings: Administration of DMHCA to NeuT/ATTAC mice beginning at two months of age reduced tumorigenesis, tumor multiplicity and suppressed fibrosis as shown by loss of collagen, fibroblast activation protein (FAP) and α-smooth muscle actin (SMA). These changes were accompanied by a marked reduction in the percentage of MDSC, and an increase in CD8+ effector T cells and PD1+/Foxp3+ CD4 T cells. Conclusion: Reduction of fibrosis, tumorigenesis and immune tolerance by DMHCA suggests that this LXR agonist may be useful for reducing tumor-associated fibrosis and in combination with immune checkpoint inhibitors that target PD1+ Treg cells for moderating immune tolerance. Unlike non-steroidal LXR agonists, DMHCA does not increase serum triglycerides or produce hepatic steatosis, and may therefore be a good candidate for clinical studies. Supported by a Sher Award, 1P30CA051008 from the NCI, NIH, to the Lombardi Comprehensive Cancer Center, and R01 HL133545 and R01 DK116567 from the NIH to M.L. Citation Format: Robert I. Glazer, Gao Sheng, Hongyan Yuan, Suman Ranjit, Jin Lu, Xun Lu, Moshe Levi. LXR agonist N,N-dimethyl-3-β-hydroxy-cholenamide, DMHCA, reduces ErbB2-dependent tumorigenesis and immune tolerance in a conditional model of mammary fibrosis [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 394.
Abstract 4806: SIRT5 inhibition causes increased oxidative stress and impairs tumor progression and metastasis
Authors: Irma Fernandez, Yashira N. Abril, Jun Y. Hong, Min Yang, Sushabhan Sadhukhan, Hening Lin, Robert Weiss
Journal: Cancer Research (2020)

Abstract Cancer cells undergo metabolic reprogramming, producing energy through aerobic glycolysis followed by lactic acid fermentation. Consequently, targeting key metabolic enzymes has emerged as a potential avenue to selectively inhibit tumor growth. The sirtuin family of deacylases has roles in both metabolism and cancer. The mitochondrial sirtuin SIRT5 regulates protein post-translational modifications on metabolic enzymes by catalyzing the removal of succinyl, malonyl, and glutaryl moieties. SIRT5 is over-expressed in many cancers, including breast cancer. Therefore, we hypothesized that SIRT5 promotes breast cancer progression by facilitating metabolic reprogramming. SIRT5 knockdown in human cancer cells inhibited anchorage independent growth but had little effect on non-transformed cells. To examine how SIRT5 loss impacts tumorigenesis in vivo, we utilized MMTV-PyMT transgenic mice, which are prone to mammary adenocarcinoma and lung metastasis. SIRT5 knockout (KO) MMTV-PyMT mice had increased survival, decreased tumor size, and reduced lung metastases, as compared to SIRT5 wild-type (WT) MMTV-PyMT controls. SIRT5 KO cancer cells had higher levels of reactive oxygen species and displayed lower levels of important antioxidants such as NADPH and GSH. These results suggest that SIRT5 KO cells are more susceptible to oxidative stress, hinting that SIRT5 may be promoting breast cancer by mitigating ROS through one or more of its key metabolic substrates. To determine the therapeutic potential of SIRT5 inhibition, we created potent and specific small molecule SIRT5 inhibitors. Pharmacological inhibition of SIRT5 impaired mammary tumor growth in both transgenic and human breast cancer xenograft mouse models, with no apparent toxicity. Considering that Sirt5 knockout mice are generally normal, with only mild phenotypes observed, these data establish SIRT5 as a promising target for treating breast cancer. Citation Format: Irma Fernandez, Yashira N. Abril, Jun Y. Hong, Min Yang, Sushabhan Sadhukhan, Hening Lin, Robert Weiss. SIRT5 inhibition causes increased oxidative stress and impairs tumor progression and metastasis [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 4806.
Abstract 1982: Development of reference material for blood tumor mutational burden measurement
Authors: Matthew G. Butler, Yves Konigshofer, Omoshile Clement, Andrew Anfora, Dan Brudzewsky, Bharathi Anekella, Russell Garlick
Journal: Cancer Research (2020)

Abstract Tumor mutational burden (TMB) is a measurement of the somatic mutations acquired by a tumor genome that cause nonsynonymous changes in proteins. TMB is a biomarker that serves as a proxy for the potential to produce neoantigens that will be recognized by T cells. Despite some reports to the contrary, TMB has successfully categorized the likelihood that an individual will respond positively to immune checkpoint inhibitors in some clinical trials. Although most TMB measurements are made from genomic DNA extracted from formalin-fixed and paraffin-embedded tissue sections, some diagnostic tests measure TMB in circulating tumor DNA (ctDNA) extracted from blood samples; an approach referred to as blood TMB (bTMB). Blood TMB is an attractive biomarker since it bypasses many of the obstacles encountered with resected and hard to biopsy tumors. Only a handful of diagnostic laboratories measure bTMB and their analytic validations rely on hard to obtain specimens acquired from ongoing drug trials or tissue repositories. This specimen scarcity impedes in depth analytic assay validation and the generation of harmonized bTMB data. For bTMB measurements to become routine, robust, and accessible to all diagnostic laboratories, we developed contrived patient-like bTMB reference materials. Blood TMB reference materials were formulated by blending and sizing genomic DNA purified from tumor and corresponding normal cell lines by proprietary methodology. Fragment analysis demonstrated that the bTMB reference materials mimic the size distribution typical of purified ctDNA. Sequencing by a targeted gene panel showed the bTMB reference materials had variant allele frequencies (VAFs) characteristic of ctDNA. For example, bTMB reference materials produced with either 2.0 or 0.5% tumor content had mean VAFs of approximately 1.0 and 0.3 %, respectively. Additional sequencing of bTMB reference materials by other gene panels demonstrated comparable results. Evaluation of contrived bTMB reference materials with various cancer gene panels will assist in the standardization of the measurement of bTMB, an emerging biomarker for clinical utility of immune checkpoint inhibitor therapy. Citation Format: Matthew G. Butler, Yves Konigshofer, Omoshile Clement, Andrew Anfora, Dan Brudzewsky, Bharathi Anekella, Russell Garlick. Development of reference material for blood tumor mutational burden measurement [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 1982.
Abstract 3510: The metabolomic profile of urine from prostate cancer patients using capillary electrophoresis mass spectrometry (CEMS)
Authors: Alexander Buko, Leo Cheng, Andrew Gustev, Adam Feldman
Journal: Cancer Research (2020)

Abstract Background: Prostate cancer (PCa) pathogenesis is influenced by alterations in cellular metabolism. Metabolomics measures these biochemical changes to create global tissue metabolite profiles. Urinary studies are noninvasive and can potentially identify biomarkers for PCa. Objective: We used Capillary Electrophoresis Mass Spectrometry (CE-MS) to analyze urine from men undergoing prostate biopsy to investigate their metabolomic profiles. Methods: We retrospectively analyzed 40 urine samples (20 from bx demonstrating PCa, 20 from benign) that were prospectively collected from men undergoing prostate biopsy. Analysis of charged metabolites done with Agilent CE-MS system (J Proteome Res. 2:488; 2003). Screening of potential biomarkers was performed with statistical protocols and pathway analyses. Metabolites with levels below the detection limit in all samples were excluded. Relative abundances of metabolites were normalized to levels of creatinine. Pathway analysis with MetaboAnalyst (Metabolites 9:57; 2019). Conclusions: CE-MS analysis identified several metabolic pathways that were altered in urine of men with PCa. These metabolites are involved in steroid, aromatic, microorganism and SCFA processes and warrant targeted studies which are underway in our lab. If validated, they have potential to serve as non-invasive biomarkers for PCa diagnosis and therapeutics Citation Format: Alexander Buko, Leo Cheng, Andrew Gustev, Adam Feldman. The metabolomic profile of urine from prostate cancer patients using capillary electrophoresis mass spectrometry (CEMS) [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 3510.