tbuckley/cabot-search huggingface dataset:
Plant flavonoid apigenin inhibits prostate carcinogenesis by suppressing β-catenin signaling pathways
Authors: Sanjeev Shukla, Gregory MacLennan, Chris Flask, Pingfu Fu, Martin Resnick, Sanjay Gupta
Journal: Cancer Research (2007)

4197  Deregulation of β-catenin signaling is an important event in the genesis of several human malignancies including prostate cancer. β-catenin is an intracellular anchoring protein and together with E-cadherin constitutes the adherent junction essential for epithelial cell homeostasis. Perturbation in the expression or function of these proteins results in loss of intercellular adhesion, with possible consequent cell transformation and cancer progression. Increased nuclear levels of β-catenin have been observed in prostate cancer, a finding that correlates with anti-apoptosis and enhanced cell invasiveness. Using the transgenic adenocarcinoma of the mouse prostate (TRAMP) model, we evaluated the efficacy of apigenin, a plant flavonoid commonly present in fruits and vegetables, in inhibiting prostate carcinogenesis and investigated its mechanism of action. Eight week old male TRAMP mice were randomly divided into three groups. Oral intake of apigenin at 20-μg/mouse/day to one group and at 50-μg/mouse/day to a second group (gavaged in 0.2 ml vehicle containing 0.5% methyl cellulose and 0.025% Tween 20) was provided for six days per week for 20 weeks; mice in the third group received vehicle only and served as controls. Studies from two independent experiments, conducted on 6 mice in each test group, showed that the cumulative incidence of prostate cancer development at 28 weeks of age in control animals was 100% (12/12) as observed by tumor palpation, whereas 75% (9/12), 42% (5/12) and 33% (4/12) of the animals exhibited distant metastases to lymph nodes, lungs, and liver. Apigenin feeding to TRAMP mice from 8-28 weeks of age was accompanied by a marked reduction in tumor growth with no evidence of metastasis. Apigenin feeding resulted in a significant decrease in dorso-lateral and ventral lobes of the prostate and genitourinary weight. Sequential MRI analysis documented that mice fed higher doses of apigenin had smaller prostate volumes than control mice and mice fed smaller doses of apigenin. Histopathological examination of apigenin-fed animals showed reduced proliferation, which correlated with serum apigenin levels. Feeding apigenin further resulted in increased levels of E-cadherin and decreased levels of nuclear β-catenin, and their key targets c-Myc and cyclin D1 in the dorso-lateral prostates. Treatment of DU145 human prostate cancer cells with 20 and 40 μM apigenin also increased protein levels of E-cadherin and reduced nuclear β-catenin expression, an effect similar to the exposure of cells to β-catenin siRNA. Diminished nuclear β-catenin levels exhibit reduced transcriptional activity, resulting in decreased c-Myc and cyclin D1. Taken together, these findings suggest that plant flavonoids, in particular apigenin may be beneficial in reducing the incidence and the aggressiveness of prostate cancer, at least in part by inhibiting β-catenin signaling pathways.
380 GS-3583, a novel FLT3 agonist Fc fusion protein, expands conventional dendritic cells in healthy volunteers
Authors: Nishanthan Rajakumaraswamy, Anees Dauki, Michelle Kuhne, Torsten Trowe, Winnie Weng, Kai-Wen Lin, Emon Elboudjwarej, Brian Carr, Angela Worth, Anshu Vashishtha, Christian Schwabe, Ahmed Othman
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Conventional dendritic cells subtype 1 (cDC1) play a vital role in the priming and expansion of tumor specific CD8+ T cells and their recruitment to tumor microenvironment (TME). However, cDC1s are often underrepresented in the TME. Systemic administration of Fms-like tyrosine kinase 3 ligand (FLT3L), a hematopoietic growth factor that binds to FLT3 on myeloid and lymphoid progenitor cells, leads to expansion of cDC1s in the periphery which can then be recruited into the TME. FLT3 pathway stimulation using GS-3583, a novel FLT3 agonistic Fc fusion protein, has the potential to promote T cell mediated anti-tumor activity. We sought to evaluate the pharmacodynamic (PD) effect of a single dose of GS-3583 in healthy volunteers alongside its safety. Herein, we present the updated results of the study. Methods This was a first-in-human, placebo-controlled study of GS-3583 in healthy volunteers to evaluate the safety, pharmacokinetics (PK), and PD of escalating single doses (ranging from 75 micrograms to 2000 micrograms) of GS-3583. The study was blinded to the subjects and the investigator. Each dose cohort enrolled 8–12 healthy subjects who received GS-3583 or placebo as single IV infusion at 3:1 ratio. Subjects were observed in the phase 1 unit for 15 days and then for 12 weeks as outpatients. As part of the PD evaluation, we investigated the changes in the number of cDC1 and cDC2 cells. Results As of 2nd July 2021, selected safety, PK and PD data from all 4 cohorts were available. GS-3583 was well tolerated and all subjects had been discharged. To date, there have been no serious or grade 3 or higher adverse events. Preliminary PK analysis suggested dose-dependent increase in GS-3583 exposure (AUC and Cmax). Preliminary PD analysis shows that administration of GS-3583 resulted in temporary, dose-dependent increases in cDC1/cDC2 cells that peaked between days 5–11 (higher doses resulted in later peaks) and returned to baseline within 3 weeks of drug administration (table 1, figure 1). Abstract 380 Table 1 Selected subject characteristics and pharmacodynamic results Abstract 380 Figure 1 A) Comparison of cDC1 cell quantitative changes in cohorts 1–4; B) Comparison of cDC2 cell quantitative changes in cohorts 1–4 Conclusions GS-3583 infusion was well tolerated and induced dose dependent expansion of dendritic cells in the periphery in healthy volunteers. In patients with cancer, this increase in dendritic cells can be utilized to enhance anti-tumor therapeutic effects of immuno-oncology therapies. Acknowledgements Funding provided by Gilead Sciences, Inc. Ethics Approval The study received study site IRB/Ethics Committee approval prior to enrollment of subjects.
Comparing Single Cord Blood Transplantation and Matched Related Donor Transplantation in Non-Remission Acute Myeloid Leukemia
Authors: Yoshimitsu Shimomura, Tomotaka Sobue, Shigeki Hirabayashi, Tadakazu Kondo, Shohei Mizuno, Junya Kanda, Takahiro Fujino, Keisuke Kataoka, Naoyuki Uchida, Tetsuya Eto, Shigesaburo Miyakoshi, Masatsugu Tanaka, Toshiro Kawakita, Hisayuki Yokoyama, Noriko Doki, Kaito Harada, Atsushi Wake, Shuichi Ota, Satoru Takada, Satoshi Takahashi, Takafumi Kimura, Makoto Onizuka, Takahiro Fukuda, Yoshiko Atsuta, Masamitsu Yanada
Journal: Blood (2021)
Immune Repertoire Analysis of Multiple Myeloma Research Samples Using NGS Characterization of Multiple B Cell Receptors in a Single Reaction
Authors: Geoffrey Lowman, Landon Pastushok, Karen Mochoruk, Wayne Hill, Michelle Toro, Loni Pickle, Carolina Gonzalez, Stephanie Ostresh, Shrutii Sarda, Chenchen Yang, Julie Stakiw, Mark J. Bosch, Hadi Alphonse Goubran, Ronald Geyer, John DeCoteau
Journal: Blood (2021)
Actions to Transform US Preventive Services Task Force Methods to Mitigate Systemic Racism in Clinical Preventive Services
Authors: Karina W. Davidson, Carol M. Mangione, Michael J. Barry, Michael D. Cabana, Aaron B. Caughey, Esa M. Davis, Katrina E. Donahue, Chyke A. Doubeni, Alex H. Krist, Martha Kubik, Li Li, Gbenga Ogedegbe, Lori Pbert, Michael Silverstein, Melissa Simon, James Stevermer, Chien-Wen Tseng, John B. Wong
Journal: JAMA (2021)

<h3>Importance</h3> US life expectancy and health outcomes for preventable causes of disease have continued to lag in many populations that experience racism. <h3>Objective</h3> To propose iterative changes to US Preventive Services Task Force (USPSTF) processes, methods, and recommendations and enact a commitment to eliminate health inequities for people affected by systemic racism. <h3>Design and Evidence</h3> In February 2021, the USPSTF began operational steps in its work to create preventive care recommendations to address the harmful effects of racism. A commissioned methods report was conducted to inform this process. Key findings of the report informed proposed updates to the USPSTF methods to address populations adversely affected by systemic racism and proposed pilots on implementation of the proposed changes. <h3>Findings</h3> The USPSTF proposes to consider the opportunity to reduce health inequities when selecting new preventive care topics and prioritizing current topics; seek evidence about the effects of systemic racism and health inequities in all research plans and public comments requested, and integrate available evidence into evidence reviews; and summarize the likely effects of systemic racism and health inequities on clinical preventive services in USPSTF recommendations. The USPSTF will elicit feedback from its partners and experts and proposed changes will be piloted on selected USPSTF topics. <h3>Conclusions and Relevance</h3> The USPSTF has developed strategies intended to mitigate the influence of systemic racism in its recommendations. The USPSTF seeks to reduce health inequities and other effects of systemic racism through iterative changes in methods of developing evidence-based recommendations, with partner and public input in the activities to implement the advancements.
B Cell Receptor Signaling Drives APOBEC3 Expression Via Direct Enhancer Regulation in Chronic Lymphocytic Leukemia B Cells
Authors: Zhiquan Wang, Huihuang Yan, Justin C. Boysen, Charla R. Secreto, Esteban Braggio, Susan L. Slager, Sameer A. Parikh, Neil E. Kay
Journal: Blood (2021)
Abstract 9383: Dapagliflozin, an Sglt2 Inhibitor, Reduces Expression of Myd88, Nlrp3 and Nf-kb During Exposure to Doxorubicin and Trastuzumab in Cellular Models
Authors: Nicola Maurea, Andrea Paccone, Martina Iovine, Simona Buccolo, Francesca Cerrone, Vincenzo Quagliariello
Journal: Circulation (2021)

Introduction: The cumulative incidence of cardiac events in women treated with anthracycline and trastuzumab at 1 year after the diagnosis of breast cancer was 16.4%, at 2 years 23.8 %, and at 3 years 28.2%. Sodium glucose cotransporter 2 inhibitors, reduces HF hospitalization and cardiovascular mortality. Hypothesis: We hypothesize that dapagliflozin could exerts cardioprotective effects in cellular models of doxorubicin and trastuzumab-induced cardiotoxicity Methods: Human cardiomyocytes (HL-1 cells) were exposed to subclinical concentration of doxorubicin and trastuzumab (100 nM) alone or in combination with dapagliflozin at 50 nM for 48h. Cell viability, apoptosis and necrosis were performed. Quantification of malondialdehyde, 4-hydroxynonenal and intracellular Ca 2+ were performed through spectrophotometric methods. Anti-inflammatory studies were also performed (expression of NLRP3 inflammasome, TLR4/MyD88 pathways, nuclear expression of NF-kB). Intracellular concentration of IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-10, IL-12, IL17-α, IL-18, IFN-γ, TNF-α, G-CSF, and GM-CSF were also performed. Results: Dapagliflozin increased cell viability during exposure to doxorubicin and trastuzumab. Dapagliflozin reduces intracellular Ca 2+ overload ( -47,6% vs cells treated only to anticancer drugs; p&lt;0,001), lipid peroxidation (mean reduction of 35-43 % compared to cells exposed only to anticancer drugs; p&lt;0,001). The expression of Myd88, NLRP3 and NF-kB was significantly reduced after treatment with dapagliflozin (-37,5, -28 and -37 % vs cells exposed only to anticancer drugs, respectively; p&lt;0.001). A specific set of cytokines, such as IL-1α, IL-1β, IL-6, IL17-α, TNF-α and IL-18 were significantly reduced after treatment with dapagliflozin indicating its anti-inflammatory, anti-fibrotic and cytoprotective properties which could prevent arrhythmic and myocardial events. Conclusions: Dapagliflozin exerts significant cardioprotective properties mediated by iCa 2+ content that consequently reduces peroxidation and NLRP3- Myd88 expression; inhibition of NLRP3 inflammasome by dapagliflozin decreased the expression of cytokines involved in cardiotoxicity.
Endoscopic submucosal dissection with double-endoscope and snare-based traction for adenoma involving the ileocecal valve
Authors: Chu-Kuang Chou, Kun-Feng Tsai, Li-Chun Chang, Chao-Wen Hsu
Journal: Endoscopy (2021)

A 2.7-cm lateral spreading tumor involved the ileocecal valve. Most of the lesion was in the terminal ileum and was very hard to approach colonoscopically ([Fig. 1], [Fig. 2]). Performing endoscopic submucosal dissection (ESD) without any additional traction would have been very demanding. The idea of double-endoscope-assisted ESD (DS-ESD) has been proposed for treatment of tumors in the cecum and distal colon [1] [2]. We used double endoscopes, one for ESD and one for traction, to pull the lesion out of the terminal ileum and resect it. We modified DS-ESD with snare-based traction, which was strong and reliable ([Fig. 3], [Fig. 4]). The traction can be adjusted during the procedure. Only around 30 minutes was required to resect this lesion ([Fig. 5]). ESD with double endoscopes and snare-based traction can make lesions involving the ileocecal valve easier to resect ([Video 1]).
Jacqueline Ann Didsbury
Authors: Julia Rawstorne
Journal: BMJ (2021)

Jacqueline Didsbury (nee Monaghan) was an extraordinary lady—beaming light, joy, and hope into our community mental health team in a dingy basement in Glasgow’s West End for 10 years.

Brought up in Bathgate, West Lothian, “wee Jac” was a proud Scot. The middle child of James and Therine Monaghan, she was educated at St Kentigern’s secondary school. She graduated with honours from Glasgow University Medical School in 2002. Academically gifted and empathetic, she chose psychiatry as a career. She met her tall, dark, and handsome future husband, Andrew, at university where they shared a flat, and married in 2004. She worked in junior doctor roles in Glasgow and was our specialty doctor in psychiatry at Riverside CMHT in Partick from 2009 …
Patients with Primary Central Nervous System Lymphoma Have High Levels of Soluble Programmed Cell Death Protein 1 in Their Pretherapeutic Cerebrospinal Fluid
Authors: Rasmus Svane Ditlev Severinsen, Marie Beck Enemark, Julie Bondgaard Mortensen, Eigil Kjeldsen, Michael Thorsgaard, Elisa Jacobsen Pulczynski, Gorm von Oettingen, Holger Jon Møller, Christopher Vejgaard, Mette Bjerre, Francesco d'Amore
Journal: Blood (2021)
HIF-Mediated and Non-HIF-Mediated Differential Gene Expressions in Sickle Cell Reticulocyte and Their Impact on Clinical Manifestations
Authors: Xu Zhang, Jihyun Song, Binal N. Shah, Jin Han, Taif Hassan, Galina Miasnikova, Adelina Sergueeva, Sergei Nekhai, Roberto Machado, Mark T. Gladwin, Santosh L. Saraf, Josef T. Prchal, Victor R. Gordeuk
Journal: Blood (2021)
Multispectral Imaging for Microchip Electrophoresis Enables Point-of-Care Newborn Hemoglobin Variant Screening
Authors: Ran An, Yuning Huang, Anne Rocheleau, Alireza Avanaki, Priyaleela Thota, Yuncheng Man, Zoe Sekyonda, Catherine Segbefia, Yvonne Adomakoh, Enoch Mensah, Isaac Odame, Umut A. Gurkan
Journal: Blood (2021)
Melanoma secretion of transforming growth factor‐β2 leads to loss of epidermal AMBRA1 threatening epidermal integrity and facilitating tumour ulceration*
Authors: I. Cosgarea, A.T. McConnell, T. Ewen, D. Tang, D.S. Hill, M. Anagnostou, M. Elias, R.A. Ellis, A. Murray, L.C. Spender, P. Giglio, M. Gagliardi, A. Greenwood, M. Piacentini, G.J. Inman, G.M. Fimia, M. Corazzari, J.L. Armstrong, P.E. Lovat
Journal: British Journal of Dermatology (2021)

For patients with early American Joint Committee on Cancer (AJCC)-stage melanoma the combined loss of the autophagy regulatory protein AMBRA1 and the terminal differentiation marker loricrin in the peritumoral epidermis is associated with a significantly increased risk of metastasis.
Abstract IA-005: Metabolic Stress in Pancreatic Cancer Progression and Therapy
Authors: Cosimo Commisso
Journal: Cancer Research (2021)

Abstract Pancreatic ductal adenocarcinoma (PDAC) cells depend on glutamine to meet their unique metabolic needs. The elevated consumption of glutamine leads to intratumoral nutrient depletion, causing metabolic stress that has the potential to impact tumor progression and therapy. We will show that nutrient stress caused by glutamine deprivation leads to the induction of epithelial-mesenchymal transition (EMT) in PDAC cells. Mechanistically, we demonstrate that glutamine deficiency regulates EMT through the upregulation of the EMT master regulator Slug, a process that is dependent on both MEK/ERK signaling and ATF4. We find that Slug is required in PDAC cells for glutamine deprivation-induced EMT, cell motility and nutrient stress survival. Importantly, we decipher that Slug is associated with nutrient stress in PDAC tumors and is required for metastasis. These results delineate a novel role for Slug in the nutrient stress response and provide insight into how nutrient depletion might influence PDAC progression. During the development of a pharmacological in vivo system aimed at mimicking glutamine stress, we have serendipitously discovered an approach to profoundly affect PDAC tumor growth and metastasis. We will outline the metabolic mechanisms underlying these effects and discuss additional targeting strategies for PDAC. Citation Format: Cosimo Commisso. Metabolic Stress in Pancreatic Cancer Progression and Therapy [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2021 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2021;81(22 Suppl):Abstract nr IA-005.
Hematopoietic Cell Transplantation of Higher CD34+ Cell Doses and Specific CD34+ Subsets Mobilized with Motixafortide and/or G-CSF Is Associated with Rapid Engraftment - a <i>Post-Hoc</i> Analysis of the Genesis Trial
Authors: Zachary D. Crees, Keith E. Stockerl-Goldstein, Michael Retting, Sarah M Larson, Arpad Illes, Giuseppe Milone, Massimo Martino, Patrick Stiff, Douglas W. Sborov, Denise L. Pereira, Ivana N. Micallef, Gemma Moreno Jiménez, Gábor Mikala, Maria Liz Paciello Coronel, Udo Holtick, John W. Hiemenz, Muzaffar H. Qazilbash, Nancy M. Hardy, Tahir Latif, Irene García-Cadenas, Ella Sorani, Liron Shemesh-Darvish, Abi Vainstein, Shaul Kadosh, John F. DiPersio
Journal: Blood (2021)
Self-Inactivating Lentiviral Vectors for Correction of Rag1 Severe Combined Immunodeficiency
Authors: K. Pike-Overzet, A.S. Wiekmeijer, M.R.M. Baert, C. Lagresle-Peyrou, A. Schambach, F. Zhang, R.C. Hoeben, S. Hacein-Bey-Abina, A.C. Lankester, R.G.M. Bredius, G.J.A. Driessen, A.J. Thrasher, C. Baum, M. Cavazzana-Calvo, J.J.M. van Dongen, F.J.T. Staal
Journal: Molecular Therapy (2013)
Epigenetic Phenocopying Expands Molecular Risk Assessment in Acute Myeloid Leukemia (Alliance)
Authors: Brian Giacopelli, Salma Abdelbaky, Kyoko Yamaguchi, Jessica Kohlschmidt, Krzysztof Mrózek, Ada C Cleary, Yue-zhong Wu, Shelley Orwick, Deedra Nicolet, Kevin R Coombes, James S. Blachly, Bayard L. Powell, Jonathan E Kolitz, William Blum, Maria R. Baer, Andrew J Carroll, Richard M. Stone, Ann-Kathrin Eisfeld, Clara D. Bloomfield, John C. Byrd, Christopher C. Oakes
Journal: Blood (2021)
Novel Genetic Subgroups Inform on Shared Pathobiology within Adult and Pediatric Burkitt Lymphoma
Authors: Nicole Thomas, Kostiantyn Dreval, Daniela S. Gerhard, Laura K Hilton, Jeremy S. Abramson, Nancy L. Bartlett, Jeffrey Bethony, Jay Bowen, Anthony Bryan, Corey Casper, Manuela Cruz, Maureen Dyer, Julie M Gastier-Foster, Alina S. Gerrie, Bruno M. Grande, Timothy C. Greiner, Nicholas B. Griner, Thomas G. Gross, Nancy Lee Harris, John D. Irvin, Elaine S. Jaffe, Fabio Leal, Jean Paul Martin, Marie-Reine Martin, Sam M. Mbulaiteye, Charles G. Mullighan, Andrew J. Mungall, Karen Mungall, Constance Namirembe, Ariela Noy, Martin Ogwang, Jackson Orem, German Ott, Hilary Petrello, Steven Reynolds, Shaghayegh Soudi, Steven H. Swerdlow, Alexandra Traverse-Glehen, Wyndham H. Wilson, Jasper Wong, Marco A. Marra, Louis M. Staudt, David W. Scott, Ryan D Morin
Journal: Blood (2021)
Magnetismm-3: An Open-Label, Multicenter, Non-Randomized Phase 2 Study of Elranatamab (PF-06863135) in Patients with Relapsed or Refractory Multiple Myeloma
Authors: Alexander Lesokhin, Shinsuke Iida, Don Stevens, Afshin Eli Gabayan, Wei Dong Ma, Sharon Sullivan, Marc-Steffen Raab
Journal: Blood (2021)
Venetoclax Reverses Metabolic Reprogramming Induced By S1P Modulator FTY720, Suppresses Oxidative Phosphorylation and Synergistically Targets Multiple Myeloma
Authors: Evgenia Rosenberg, Valeria Voevoda, Hila Magen, Olga Ostrovsky, Avichai Shimoni, Amnon Peled, Arnon Nagler, Katia Beider
Journal: Blood (2021)
Covid-19: Ten Conservative MPs and peers referred companies to “VIP lane” that won £1.6bn of PPE contracts
Authors: Jacqui Wise
Journal: BMJ (2021)

Ten Conservative MPs and peers referred companies through the government’s “VIP lane” for personal protective equipment (PPE) contracts, a leaked document has revealed.1

The document, first seen by the Politico website,2 details 47 companies referred to the government’s high priority list for contracts to supply PPE during the covid-19 pandemic. There were £1.6bn worth of contracts awarded as a result of referrals from Conservative politicians. No other political party successfully referred companies through this fast tracked route.

A report by the National Audit Office last year found that firms referred through the VIP lane had a 10 times greater success rate for securing contracts than companies whose bids were processed through normal channels.3

On 18 October the UK’s data privacy watchdog, the Information Commissioner’s Office, ordered the government to reveal the names of the companies placed in the VIP lane within 35 calendar days.45 The ruling came after a complaint from the non-profit campaign group the Good Law Project that the Department of Health and Social Care for England had failed to comply …
Upfront Targeted Tyrosine Kinase Inhibitor Therapy Improves Outcome in Patients with Myeloid/Lymphoid Neoplasms with Eosinophilia
Authors: Yumeng Zhang, Chuanyi M. Lu, Endi Wang, Lynh Nguyen, Marietya Lauw, Somedeb Ball, Ning C. Dong, Lynn C. Moscinski, Onyee Chan, Seongseok Yun, Lubomir Sokol, Bijal D. Shah, Jeffrey E. Lancet, Andrew T. Kuykendall, Eric Padron, Ling Zhang
Journal: Blood (2021)
Adolescents and Young Adults with Immune Thrombocytopenia (ITP): A Project of the Carmen-France and Parc-ITP Registry
Authors: Alexandra Schifferli, Guillaume Moulis, Bertrand Godeau, Thierry Leblanc, Marc Michel, Nathalie Aladjidi, Guy Leverger, Mohsen Saleh Elalfy, John Grainger, Meera B. Chitlur, Andrea Heiri, Susanne Holzhauer, Thomas Kuehne
Journal: Blood (2021)