tbuckley/cabot-search huggingface dataset:
Spatial resolution of SARS-CoV-2 lung infection
Authors: Luisanna Pia
Journal: Nature reviews. Immunology (2020)

role of HDAC3 as a transcriptional repressor.A machine-learning approach revealed DNA sequences associated with DA-independent and DA-dependent genomic regions bound by HDAC3 that could predict transcriptional outcome.In particular, binding of the co-factor ATF2 was associated with DA-independent sites whereas ATF3 binding was associated with DA-dependent sites.In keeping with this, LPS stimulated the transcription of a DA-independent reporter gene containing the ATF2 motif in the presence of ATF2 and inactive HDAC3, whereas LPS-mediated repression of a DA-dependent reporter gene with
AB0049B CHANGES OF INNATE LYMPHOID CELLS IN PERIPHERAL BLOOD OF PATIENTS WITH PRIMARY SJöGREN’S SYNDROME AND ITS CORRELATIONS WITH CLINICAL MARKERS
Authors: Hui Chu, Zhen Tan, Xuan Fang, Ruolan Wu, Ke Wang, LI Xiangpei, Guosheng Wang, Yiping Wang, Xiaomei Li
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Innate Lymphoid Cells (ILCs) are a novel group of innate immune cells, according to the cytokine profile, they were divided into three major subsets: ILC1(Lin–IL7R+NKp46+ILCs), ILC2(Lin–IL7R+CRTH2+ILCs) and ILC3(Lin–IL7R+CRTH2–CD117+ILCs)<sup>[1]</sup>. Little research on ILC in the pathogenesis of Primary Sjögren's Syndrome(primary SS) <h3>Objectives:</h3> Our purpose is to explore the function and role of ILC in the pathogenesis of Primary Sjögren's Syndrome and its correlations with clinical markers. <h3>Methods:</h3> 20 patients with pSS and 15 age-matched healthy non-immune-related diseases controls were enrolled. The frequency of ILCs, B cells, CD4+T and CD8+T cells from PBMCs was detected by flow cytometry. Analysis the subsets of ILCs in each group which compared with B cells and T cell subsets respectively and correlation with clinical serologic markers. Analyze the levels of IL-4, IL-9, IL-33, IL-22 and IFN-γ in each group by ELISA. <h3>Results:</h3> Compared with the control group, the percentage of ILC was decreased significantly in primary SS(<i>P</i>&lt;0.0001); Meanwhile ILC1 was significantly increased in primary SS(<i>P</i>&lt;0.0001), ILC2 was decreased significantly in primary SS(<i>P</i>=0.0009) and ILC3 has no significant difference in the primary SS (<i>P</i>&gt;0.05). The frequency of ILCs in all patients positively correlated with antinuclear antibody titer (ANA(D)) (r=0.295, <i>P</i>=0.0133), moreover, the frequency of ILC2 in primary SS was positively correlated with B cells(r=0.3896;<i>p</i>&lt;0.05), and the serum IgG was negatively correlated with ILC2 of all patients (r=0.2091,<i>P</i>=0.0427). Compared with Healthy control group, the level of IL-22 was significant higher in primary SS(<i>P</i>=0.0003), however, the levels of IL-4, IL-9, IL-33 and IFN-γ were not significant different with healthy control group(<i>P</i>&gt;0.05). <h3>Conclusion:</h3> The frequency of ILCs is related to ANA(D) of primary SS patients and ILCs play a critical role in the pathogenesis of primary SS. Its function and mechanism are worth further exploration. <h3>Reference</h3> [1] Spits H., Artis D., Colonna M., et al. Innate lymphoid cells-a proposal for uniform nomenclature[J]. Nat Rev Immunol, 2013, 13(2): 145-149. doi: 10.1038/nri3365 <h3>Disclosure of Interests:</h3> None declared
FRI0184 Angiotensin-converting enzyme and anti-angiotensin-converting enzyme antibodies in systemic sclerosis
Authors: RT Alekperov, ML Stanislav, MA Myagkova, TV Abramenko, OA Kost, None Nikolskaya
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> To investigate the levels of angiotensin-converting enzyme (ACE) and anti-angiotensin-converting enzyme antibodies (ACEab) in patients with systemic sclerosis (SSc). <h3>Methods</h3> Thirty five patients with systemic sclerosis, age 50,0 ± 11,7 (mean ± SD), range 27–71 years, were included in the study. Duration of disease ranged from 1 to 20 years, means 7,0 ± 5,2. Thirteen pts had diffuse systemic sclerosis (dSSc), twenty two had limited systemic sclerosis (lSSc). Ten healthy subjects were selected as controls. Spectrofluorimetry for detection of ACE and ELISA for ACEab were used. <h3>Results</h3> We revealed the two-fold lower levels of ACE in SSc pts compared with controls (0,022 ± 0,021 vs 0,044 ± 0,028; ð = 0,012). There were no differences in ACE values observed between the dSSc and lSSc groups (0,019 ± 0,017 and 0,024 ± 0,024 respectively). The lowest levels of ACE were found in SSc pts treated with inhibitors of ACE (0,013 ± 0,010), but was not statistically different from those of untreated SSc pts. In SSc pts, a positive correlation was detected between the levels of ACE and erythrocyte sedimentation rate (r = 0,505; p = 0,019), fibrinogen (r = 0,578; p = 0,015), titers of antinuclear antibodies (r = 0,529; p = 0,029). The levels of ACEab in SSc pts were similar to those of the control group (0,180 ± 0,190 and 0,208 ± 0,057, respectively). However, the ACEab levels in pts with dSSc were significantly higher than those in lSSc pts (0,29 ± 0,24 vs 0,14 ± 0,16; p = 0,041). Comparable to lSSc group impaired results were also seen in pts treated with ACE inhibitors (0,1642 ± 0,1093). The ACEab levels positively correlated with ANA titers only in dSSc pts (r = 0,835; p = 0,019). There was no relation between the ACE and ACEab levels neither in SSc pts nor in controls. <h3>Conclusion</h3> ACEab can be involved in pathogenesis of SSc and further investigation is needed.
Calcitonin (CT) is a potent inducer of prostate cancer cell proliferation and tumor progression
Authors: Shibu Thomas, Srinivasulu Chigurupati, Rajiv S. Nallu, Girish V. Shah
Journal: Cancer Research (2005)

3939  Neuroendocrine differentiation in prostate cancer has been associated with tumor progression, androgen independence and poor prognosis. Neuropeptides such as bomesin and calcitonin (CT) increase growth, invasiveness and chemoresistance of prostate cancer cell lines. Expression of CT and CTR mRNAs in primary prostate tumors is selectively epithelial, is restricted to the basal compartment of normal prostate epithelium, but is observed in whole epithelium of malignant prostates. Moreover, cells of low-grade tumors or indolent cell lines such as LNCaP or PC-3 express either CT or CTR. In contrast, cells of high-grade tumors and metastatic PC-3M cells co-express CT and CTR mRNAs. The present studies examined the effect of CT/CTR co-expression on cell proliferation, colony-formation and tumorigenicity of prostate cancer cell lines. Three prostate cancer cell lines PC-3 (which expresses CT but not CTR), LNCaP (expresses CTR but not CT) and PC-3M (co-expresses CT and CTR) were used in the study. The expression of CTR in PC-3 cells was initiated by stably expressing mammalian expression vector pcDNA3.1 containing CTR cDNA. Similarly, LNCaP cells were stably transfected with pcDNA3.1-CT vector. The expression of CT in PC-3M cells was either increased or knocked-down appropriately using either pcDNA3.1-CT vector or anti-sense CT ribozyme. The derived cell lines were then characterized for the expression of respective proteins by the abundance of the respective gene as well as for protein expression by either radioimmuno- or radioreceptor assays. The cell lines were then tested for cell proliferation by MTT assay, for colony-forming ability on soft agar and tumorigenicity in nude mice. PC-3-CTR cell lines displayed greater than two-fold increase in cell proliferation as compared to PC-3 cells transfected with carrier plasmid. The PC-3-CTR cells also formed several-fold larger and more numerous colonies in soft agar as compared to control cells. Similarly, LNCaP-CT cells also markedly increased their adhesion to plastic, and cell proliferation. PC-3M-CT cell lines also showed dramatically different phenotypes as indicated by marked decrease in their adhesion properties, increased cell proliferation, colony formation, and moderately greater ability of forming tumors in nude mice as compared to PC-3M cells transfected with a carrier plasmid. However, most dramatic results were obtained with PC-3M-CTnull cells, which were obtained by stable transfection of anti-sense CT hammerhead ribozymes. These cells displayed markedly lower proliferation rate, and an extremely small tumor (over 100-fold smaller than those formed in controls) was formed in only one of six mice injected with these cells. These results suggest that CT serves as a potent promoter of prostate cancer progression, and co-expression of CT with CTR significantly enhances the ability of CT to accelerate this process.
Abstract 6380: Suppression of the solar ultraviolet-induced skin carcinogenesis by TOPK inhibitor HI-TOPK-032
Authors: Eunmiri Roh, Yaping Han, Kanamata Reddy, Tatyana A. Zykova, Mee Hyun Lee, Ke Yao, Ruihua Bai, Clara Curiel-Lewandrowski, Zigang Dong
Journal: Cancer Research (2020)

Abstract Non-melanoma skin cancer (NMSC) such as cutaneous squamous cell carcinoma (cSCC) is caused by solar ultraviolet (SUV) exposure and is the most common cancer in the United States. T-LAK cell-originated protein kinase (TOPK), a serine-threonine kinase is activated by SUV irradiation and involved in skin carcinogenesis. Strategies with research focusing on the TOPK signaling pathway and targeted therapy in skin carcinogenesis may helpful for the discovery of additional treatments against skin cancer. In this study, we found that TOPK can directly bind to and phosphorylate c-Jun (as one of the core member of AP-1) at Ser63 and Ser73 after SSL exposure in a JNKs-independent manner. TOPK knocking down, or HI-TOPK-032 (TOPK specific inhibitor) attenuated colony formation and cell proliferation of skin cancer cells. Phosphorylated levels of c-Jun were overexpressed in human AK and cSCC compared to normal skin tissues, and HI-TOPK-032 inhibited the phosphorylation of c-Jun in SCC cell line in a dose-dependent manner. Furthermore, HI-TOPK-032 decreased SSL-induced AP-1 transactivation activity. Moreover, acute SSL-induced inflammation was attenuated by the topical application of HI-TOPK-032 in SKH1 hairless mice. Importantly, HI-TOPK-032 suppressed chronic SSL-induced skin carcinogenesis and c-Jun phosphorylation levels in SKH1 hairless mice. Our results demonstrate that TOPK can phosphorylate and activate c-Jun at Ser63 and Ser73 in the process of skin carcinogenesis and HI-TOPK-032 could be used as a potential chemopreventive drug against cSCC development. Citation Format: Eunmiri Roh, Yaping Han, Kanamata Reddy, Tatyana A. Zykova, Mee Hyun Lee, Ke Yao, Ruihua Bai, Clara Curiel-Lewandrowski, Zigang Dong. Suppression of the solar ultraviolet-induced skin carcinogenesis by TOPK inhibitor HI-TOPK-032 [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 6380.
Necroptosis restricts influenza A virus as a stand-alone cell death mechanism
Authors: Maria Shubina, Bart Tummers, David F. Boyd, Ting Zhang, Chaoran Yin, Avishekh Gautam, Xi-zhi J. Guo, Diego A. Rodriguez, William J. Kaiser, Peter Vogel, Douglas R. Green, Paul G. Thomas, Siddharth Balachandran
Journal: The Journal of Experimental Medicine (2020)

Influenza A virus (IAV) activates ZBP1-initiated RIPK3-dependent parallel pathways of necroptosis and apoptosis in infected cells. Although mice deficient in both pathways fail to control IAV and succumb to lethal respiratory infection, RIPK3-mediated apoptosis by itself can limit IAV, without need for necroptosis. However, whether necroptosis, conventionally considered a fail-safe cell death mechanism to apoptosis, can restrict IAV—or indeed any virus—in the absence of apoptosis is not known. Here, we use mice selectively deficient in IAV-activated apoptosis to show that necroptosis drives robust antiviral immune responses and promotes effective virus clearance from infected lungs when apoptosis is absent. We also demonstrate that apoptosis and necroptosis are mutually exclusive fates in IAV-infected cells. Thus, necroptosis is an independent, “stand-alone” cell death mechanism that fully compensates for the absence of apoptosis in antiviral host defense.
Abstract 6491: Prognostic potential of carcinoembryonic antigen expression patterns in lung adenocarcinoma
Authors: Ming-Yi Zheng, Yen-Shou Kuo, Yu-Ting Chou
Journal: Cancer Research (2020)

Abstract Carcinoembryonic antigen (CEA) is one of the most commonly used tumor markers. Although the suitability of CEA as an effective marker for lung cancer remains debatable, characteristics such as noninvasiveness and lack of other reliable markers make CEA an attractive option in lung cancer. Divergent CEA expression patterns before and after EGFR-tyrosine kinase inhibitor (TKI) treatment have been reported. However, whether these patterns are associated with tumor progression remain elusive. We hypothesized that divergent patterns of serum carcinoembryonic antigen at initial diagnosis (CEAIn) and disease progression (CEAPd) may reflect the diversity of lung cancer cells selected by TKI, conferring distinct progression profiles in patients. Our objective was to verify the prognostic potential of divergent CEA patterns before and after TKI treatment in lung cancer patients with wild-type or mutant EGFR. Of the 1736 lung cancer patients identified from the cancer registry group between 2011 to 2016, we selected 517 patients with advanced stage adenocarcinoma, data on EGFR mutation status and CEAIn, among whom were 288 patients with data on CEAPd, eligible for inclusion in the correlation analysis of clinical characteristics and survival. EGFR wild-type lung adenocarcinoma patients displayed lower CEAIn level than those with EGFR mutations. Multivariable analysis revealed that CEAIn expression was associated with poor progression-free survival in patients harboring mutant EGFR but not in those with wild-type EGFR. Moreover, CEAIn and CEAPd were associated with the good and poor post-progression survival, respectively, only in the EGFR-mutant and not in the wild-type group. In vitro cell line experiments revealed that CEA expression, cancer dissemination, and chemoresistant properties can be affected by EGFR-TKI selection. EGFR-mutant patients, exhibiting high CEAIn (≥ 5 ng/mL) and low CEAPd (&amp;lt; 5 ng/mL), showed a potential toward displaying new metastasis. Our findings support the notion that EGFR mutation status is a critical factor in determining prognostic potential of CEAIn and CEAPd in patients under EGFR-TKI treatment, and divergent CEAIn and CEAPd patterns are associated with distinct cancer progression profiles. Citation Format: Ming-Yi Zheng, Yen-Shou Kuo, Yu-Ting Chou. Prognostic potential of carcinoembryonic antigen expression patterns 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 6491.
SAT0032 Prevalence of uveitis and sjÖgren’s syndrome (ss) in portuguese patients with ankylosing spondylitis
Authors: J Figueirinhas, J Vaz Patto, MM Silva, J Gil Forte, LN Ferraz de Oliveira
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> To evaluate the prevalence of uveitis, SS and Sicca syndrome (SicS) in patients with AS. To analise the epidemiological data (Sex, age and presence of HLA B27). <h3>Methods</h3> We included 86 patients with AS, 61 men (70.9%) and 25 women (29.1%), mean age was 48.6 ± 11.8 years (range 22 -71). The disease onset had occurred at 27.4 ± 9.2 years (range 6–53). The diagnosis of SS was made according to European Criteria and all patients with SS had keratoconjuntivitis sicca. <h3>Results</h3> Uveitis was present in 30 patients (34.9%), SS in 8 patients (9.3%) and HLA-B27 + in 63 patients (73.3%). In the group of female patients (25) we found: 22 (88%) HLA-B27 +, 10 (40%) with uveitis, 8 (32%) with SicS and 1 (4%) with SS. In the group of male patients (61) we found: 41 (67.2%) HLA-B27 +, 20 (32.8%) with uveitis, 12 (19.7%) with SicS and 7 (11.5%) with SS. In the group of HLA-B27 + patients (62 we found: 26 (41.9%) with uveitis and 6 (9.7%) with SS. In the group of HLA-B27 negative patients (24) we found: 4 (16.7%) with uveitis and 2 (8.3%) with SS. <h3>Conclusion</h3> The prevalence of HLA-B27 was lower than in literature. HLA-B27 was more prevalente in female. The frequence of uveitis was higher in the HLA-B27 positive patients. We find a high prevalence of SS in male. <h3>References</h3> Brito A, Figueirinhas J, Ramos M, <i>et al</i>. Sindroma de Sjögren. Acta Médica Port. 1994;7:565–76 Vaz Patto J, Figueirinhas J, Gil Forte J, <i>et al</i>. Sjögren's syndrome associated with Rheumatoid Arthritis. V International Symposium on Sjögren's Syndrome, Noordwijkerhout, 1995. <i>Clin Rheum</i>. 1995;14(Suppl 1):53 Figueirinhas J, Gil Forte J, Vaz Patto J, <i>et al</i>. Immunogenetics of Sjögren's syndrome in Portuguese patients. First International Symposium on Occular Immunology and Inflammation, Amsterdam, 1998. <i>Occul Immunol Inflamm</i>. 1998;<b>6</b>(Suppl):68
Abstract DDT02-04: GDC-9545: Discovery of an oral estrogen receptor antagonist, degrader, and immobilizer for the treatment of ER+ breast cancer patients
Authors: Xiaojing Wang, Xiaojing Wang
Journal: Cancer Research (2020)

Abstract GDC-9545: Discovery of an orally bioavailable pure antiestrogen for the treatment of ER+ breast cancer patients. Breast cancer affects one out of every eight women in their lifetime making it the most frequently occurring cancer among women. Mortality remains high with more than 40,000 of women expected to die of breast cancer in 2019 in the U.S alone. Approximately 70% of all breast cancer expresses estrogen receptor alpha (ERα), making it a prime target for the treatment of breast cancer. Despite effective endocrine therapies, many patients eventually relapse and become resistant to standard of care treatments. These endocrine resistant tumors often continue to depend on ERα for growth and survival, as evidenced by their sensitivity to the selective estrogen receptor antagonist and degrader, fulvestrant. However, fulvestrant is limited by its pharmaceutical and pharmacokinetic properties and its intramuscular route of administration to achieve sufficient target occupancy. Consequently, selective ERα ligands with desirable mechanisms of action and superior drug properties were sought after, allowing consistent and rapid achievement of therapeutic exposure. We have reported previously of our first and second generations of orally available ERα ligands, GDC-0810 and GDC-0927 respectively. Targeting a pure antiestrogen profile and guided by co-crystal structures, we identified a structurally distinct scaffold from these first two generations. Fine-tuning the physiochemical properties while balancing potency and efficacy culminated into a third generation development candidate GDC-9545. GDC-9545 immobilizes ERα to achieve full antagonism and degradation. It inhibits tumor growth or causes tumor regression in patient derived xenograft mouse models. It is orally bioavailable and has high safety margins in preclinical species. GDC-9545 is currently in active clinical testing. Citation Format: Xiaojing Wang, Xiaojing Wang. GDC-9545: Discovery of an oral estrogen receptor antagonist, degrader, and immobilizer for the treatment of ER+ breast cancer patients [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 DDT02-04.
Cooling at Tokyo 2020: the why and how for endurance and team sport athletes
Authors: Lee Taylor, Sarah Carter, Trent Stellingwerff
Journal: British Journal of Sports Medicine (2020)

The Tokyo 2020(1) Olympics are expected to be the hottest in modern history,1 resulting in much conjecture within the literature.2–5 Long-term (~10 to 14 days) heat acclimation/acclimatisation (HA) is the gold-standard strategy to protect against heat-mediated performance decrements and exertional heat illnesses (EHI).6 Short-term heat reacclimation (~5 days), proximal to competition, can also be incorporated within athlete training and taper programmes, complimenting the earlier long-term HA. This approach allows the balance of training/load and HA agendas within the often time poor and logistically challenging elite sport environment.5 7 8

With the assumption that athletes arrive robustly heat acclimated/acclimatised to Tokyo 2020(1), practitioners have a variety of precooling, during(mid) and postcooling event interventions to consider on competition day – that are complimentarily to – rather than instead of HA.8 In brief, these can include various combinations of: (i) internal (ice slurry ingestion, cold water ingestion, etc) and external (any cold fluid, medium or air source the body is immersed or exposed to) body cooling interventions to reduce body tissue temperatures [eg, core (Tc), muscle (Tmu) and skin (Tsk) temperature (see figure 1 for summary)]8–10; (ii) interventions to evoke local cooling sensations (eg, menthol mouth rinse) which could be favourably interpreted (ie, their perception) by higher brain centres without altering Tc11 and (iii) titration of competition warm-up procedures and/or alterations in pacing, tactics and/or strategy. At the recent 2019 IAAF World Athletics Championships (Doha, Qatar), LT …
Articular cartilage regeneration by activated skeletal stem cells
Authors: Matthew P. Murphy, Lauren S. Koepke, Michael T. Lopez, Xinming Tong, Thomas H. Ambrosi, Gunsagar S. Gulati, Owen Marecic, Yuting Wang, Ryan C. Ransom, Malachia Y. Hoover, Holly Steininger, Liming Zhao, Marcin P. Walkiewicz, Natalina Quarto, Benjamin Levi, Derrick C. Wan, Irving L. Weissman, Stuart B. Goodman, Fan Yang, Michael T. Longaker, Charles K. F. Chan
Journal: Nature Medicine (2020)