tbuckley/cabot-search huggingface dataset:
Abstract PO-051: PANOVA-3: A phase III study of tumor treating fields with nab-paclitaxel and gemcitabine for front-line treatment of locally advanced pancreatic adenocarcinoma
Authors: Vincent J. Picozzi, Teresa Macarulla, Philip A. Philip, Carlos R. Becerra, Tomislav Dragovich
Journal: Cancer Research (2021)

Abstract Tumor Treating Fields (TTFields) are a non-invasive, loco-regional antimitotic treatment modality, approved for the treatment of glioblastoma and malignant pleural mesothelioma. TTFields at a specific frequency (150-200 kHz) are delivered via arrays placed on the skin surrounding the tumor site. TTFields predominantly act by disrupting the formation of the mitotic spindle during metaphase. TTFields were effective in multiple preclinical models of pancreatic cancer. The Phase 2 PANOVA study, the first trial testing TTFields in pancreatic cancer patients, demonstrated the safety and preliminary efficacy of TTFields when combined with nab-paclitaxel and gemcitabine in both metastatic and locally advanced pancreatic adenocarcinoma (LAPC). The Phase 3 PANOVA-3 trial (NCT03377491) is designed to test the efficacy and safety of adding TTFields to nab-paclitaxel and gemcitabine combination in LAPC. Patients (N = 556) with unresectable, LAPC (per NCCN guidelines) will be enrolled in this prospective, randomized trial. Patients should have an ECOG score of 0-2 and no prior progression or treatment. Patients will be stratified based on their performance status and geographical region, and will be randomized 1:1 to TTFields plus nab-paclitaxel and gemcitabine or to nab-paclitaxel and gemcitabine alone. Chemotherapy will be administered at standard dose of nab-paclitaxel (125 mg/m2) and gemcitabine (1000 mg/m2) on day 1, 8, and 15 of a 28 day cycle. The protocol has recently been amended to incorporate the use of a smaller, lighter (weight reduced from 6 to 2.7 lbs.) TTFields device. TTFields (150 kHz) will be delivered at least 18 hours/day until local disease progression per RECIST Criteria V1.1. Follow up will be performed q4w, including a CT scan of the chest and abdomen q8w. Following local disease progression, patients will be followed monthly for survival. Overall survival will be the primary endpoint. Progression-free survival, objective response rate, rate of resectability, quality of life, and toxicity will all be secondary endpoints. Sample size was calculated using a log-rank test comparing time to event in patients treated with TTFields plus chemotherapy with control patients on chemotherapy alone. PANOVA-3 is designed to detect a hazard ratio 0.75 in overall survival. Type I error is set to 0.05 (two-sided) and power to 80%. Citation Format: Vincent J. Picozzi, Teresa Macarulla, Philip A. Philip, Carlos R. Becerra, Tomislav Dragovich. PANOVA-3: A phase III study of tumor treating fields with nab-paclitaxel and gemcitabine for front-line treatment of locally advanced pancreatic adenocarcinoma [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 PO-051.
Abstract 9400: Mitral Valve Prolapse Induces Regionalized Left Ventricular Fibrosis
Authors: Jordan E Morningstar, Cortney Gensemer, Reece Moore, Diana B Fulmer, Tyler Beck, Christina Wang, Kelsey Moore, Lilong Guo, Ayesha Vohra, Franz Sieg, Yasufumi Nagata, Philippe Bertrand, Ricardo Spampinato, Janiece Glover, Stephen Poelzing, Robert G Gourdie, William Richardson, Robert A Levine, Michael Borger, Russell A Norris
Journal: Circulation (2021)

Introduction: Imaging studies patients with mitral valve prolapse (MVP) have previously shown cross sectional evidence of left ventricular (LV) fibrosis as well as increased risk for sudden cardiac death. This, along with evidence for post-repair ventricular dysfunction in Mitral valve surgery patients support a link between fibrosis and MVP. The development of fibrosis as a result of MVP, however, remains poorly understood. Hypothesis: Regionalized LV Fibrosis in MVP patients is driven by increased mechanical tension through the chordae tendineae by billowing leaflets. Methods: We performed histopathologic analysis on cardiac biopsies of 6 patients who underwent surgical repair for MV prolapse. We additionally performed longitudinal histopathologic analysis on hearts harvested from a mouse modal of human non-syndromic MVP (Dzip1 S14R/+). To assess the cellular response to increased mechanical tension, pathological stretch assays on human cardiac fibroblasts were performed in tandem with RNA seq, as well ATP luminescence assays to assess ATP release from stretched cells. Results: Biopsies from peripapillary regions, inferobasal wall, LV septum, and LV apex demonstrated regionalized myocardial fibrosis that correlated with increased macrophages and myofibroblasts. Our mouse model demonstrated similar regionalized deposition of collagen that increased over time, as well as an increase in macrophages and myofibroblasts. Stretching of human cardiac fibroblasts caused significant changes in 232 transcripts (Bonferroni corrected P value &lt;1.72*10-6), and pushed fibroblasts into a pro-fibrotic state, upregulating alpha-Smooth Muscle actin, Collagen, PLOD1, and decreasing MMP1. Additionally, pathologic stretch of fibroblasts increased secretion of ATP, a known chemoattractant for innate inflammatory cells. Conclusions: A mouse model of human MVP phenocopied regionalized myocardial fibrosis seen in humans and will provide a useful tool to investigate mechanisms of myocardial fibrosis in MVP patients. Stretch initiates changes in pro-fibrotic gene transcription, and causes ATP release from human cardiac fibroblasts.
Dose Reduced Chemotherapy in Sequence with Blinatumomab for Newly Diagnosed Older Patients with B-Precursor Adult Lymphoblastic Leukemia (ALL): Results of the Ongoing GMALL Bold Trial
Authors: Nicola Goekbuget, Andrea Stoltefuß, Max Topp, Stefan Schwartz, Andrea Renzelmann, Christoph Faul, Bernd Hertenstein, Vladan Vucinic, Maria Wachsmuth, Anne C Wilke, Lena Baumann, Diana Tichy, Monika Brüggemann, Andreas Viardot
Journal: Blood (2021)
Comparison of Salvage Intensive Chemotherapy Versus Venetoclax Combined Regimen in Patients with Relapsed/Refractory Acute Myeloid Leukemia (AML)
Authors: Silvia Park, Hee-Je Kim, Byung Sik Cho, Yoo-Jin Kim, Gi June Min, Sung-Soo Park, Seung-Ah Yahng, Young-Woo Jeon, Seung-Hwan Shin, Jae-Ho Yoon, Sung-Eun Lee, Ki-Seong Eom, Seok Lee, Chang-Ki Min, Seok-Goo Cho, Jong Wook Lee
Journal: Blood (2021)
Bioprosthetic Mitral Valve Thrombosis
Authors: Gabriel Châteauneuf, Hugo De Larochellière, Marie-Annick Clavel, Dimitri Kalavrouziotis, Eric Charbonneau, François Dagenais, Francis Morin, Iria Silva, Pierre-Yves Turgeon, Jean-Michel Paradis, Mathieu Bernier, Jonathan Beaudoin, Sébastien Bergeron, Josep Rodés-Cabau, Siamak Mohammadi, Philippe Pibarot, Kim O’Connor, Erwan Salaun
Journal: JACC. Cardiovascular imaging (2021)
Abstract 14462: Comparison of the Effectiveness and Safety of Direct Oral Anticoagulants With the Vitamin K Antagonist Warfarin in Patients With Atrial Fibrillation and Active Cancer
Authors: Taku Yasui, Wataru Shioyama, Makiko Oboshi, Toru Oka, Masashi Fujita
Journal: Circulation (2018)

Introduction: The direct oral anticoagulants (DOACs) are widely used for prevention of thromboembolic events in atrial fibrillation (AF) patients. Cancer is associated with a prothrombotic state as...
Effect of the NAMPT Activator P7C3-A20 on γ-Globin Expression in Baboon CD34+ Erythroid Cell Cultures
Authors: Vinzon Ibanez, Kestis Vaitkus, Jagadeesh Ramasamy, Yogenthiran Saunthararajah, Robert E. Molokie, Donald Lavelle
Journal: Blood (2021)
Single Cell Transcriptome Profile of Myeloma and Immune Cell Characteristics in Patients with Durable Response Post CART
Authors: Yan Asmann, Ying Li, Taxiarchis Kourelis, Moritz Binder, Wilson I Gonsalves, Henan Zhang, Anatilde Gonzalez Guerrico, Zuoyi Shao, Prashant Kapoor, David Dingli, Rahma M Warsame, Haidong Dong, Shaji Kumar, Yi Lin
Journal: Blood (2021)
Distinct Modes of Ongoing Antigen Interactions Shape Intraclonal Dynamics in Splenic Marginal Zone Lymphoma
Authors: Laura Zaragoza-Infante, Andreas Agathangelidis, Valentin Junet, Nikos Pechlivanis, Triantafylia Koletsa, Alessio Bruscaggin, Zadie Davis, Sotiria Markantonatou, Valeria Spina, Aurelie Verney, Anastasia Iatrou, Fotis Psomopoulos, David Oscier, Alexandra Traverse-Glehen, Maria Papaioannou, Davide Rossi, Anastasia Chatzidimitriou, Kostas Stamatopoulos
Journal: Blood (2021)
Interim Analyses of Overall Survival (OS) from the TOURMALINE MM3 &amp; MM4 Studies of Ixazomib Maintenance Following Primary Therapy in Multiple Myeloma (MM)
Authors: Meletios A. Dimopoulos, S. Vincent Rajkumar, Sagar Lonial, Wee-Joo Chng, Shinsuke Iida, Maria-Victoria Mateos, Gareth J. Morgan, Arun Kumar, Kaveri Suryanarayan, Alexander Vorog, Andrew Fergus, Richard Labotka
Journal: Blood (2021)
Procoagulant Platelet Subpopulation As a Novel Predictive Biomarker of Poor Outcomes in Essential Thrombocythemia
Authors: Christine Shu Mei Lee, Kristen L Estabrooks, Kaitao Lai, Agnibesh Dey, Jonathan Cheng, Shane Whittaker, Chuen Wen Tan, Heather Campbell, Hai Po Helena Liang, Ibrahim Tohidi-Esfahani, Vivien Chen
Journal: Blood (2021)
<i>Invasive Aspergillosis in Allogeneic Hematopoietic Stem Cell Transplantation Recipients: A Large Cohort Single-Center Study</i>
Authors: Yuliya A. Rogacheva, Vladislav V. Markelov, Marina O. Popova, Alisa G. Volkova, Ilya Y. Nikolaev, Olga N. Pinegina, Svetlana M. Ignatyeva, Tatiyana S. Bogomolova, Sergey N. Bondarenko, Nikolay N. Klimko, Alexander D. Kulagin
Journal: Blood (2021)
Deep Profiling of Chronic Lymphocytic Leukaemia (CLL) and Healthy Immune Cells By Mass Cytometry Resolves Impacts of Venetoclax Pressure
Authors: Charis E Teh, Tania Tan, Marie Trussart, Mengxiao Luo, Rachel Thijssen, Andrew W Roberts, David C.S. Huang, Terence Speed, Mary Ann Anderson, Daniel Gray
Journal: Blood (2021)
Abstract 9462: Emergency versus Delayed Coronary Angiogram in Survivors of Out-of-Hospital Cardiac Arrest Without St Segment Elevation: Results of the EMERGE Trial
Authors: Christian Spaulding, Caroline Hauw-Berlemont, Lionel Lamhaut, Jean-Luc Diehl, Christophe Andreotti, Olivier Varenne, Pierre Leroux, Jean Baptiste Lascarrou, Patrice GUERIN, Thomas Loeb, Eric Roupie, Cedric Daubin, Farzin Beygui, AurÃ©lie Vilfaillot, Sophie Glippa, Juliette Djadi-Prat, Gilles Chatellier, Alain Cariou
Journal: Circulation (2021)

Introduction: In adults, the most common cause of out-of-hospital cardiac arrests (OHCA) is coronary artery disease. If an immediate coronary angiogram (CAG) is recommended for survivors presenting a ST segment elevation (ST +) on the electrocardiogram (ECG) performed after resuscitation, there is still a debate regarding the best strategy in patients without ST +. Hypothesis: Performing an immediate CAG after an OHCA without ST + on the post-resuscitation ECG and no obvious non-cardiac cause of arrest leads to a better outcome. Methods: The EMERGE trial is a multicenter, randomized, controlled trial that assessed the 180-day survival rate with no or minimal neurologic sequel in patients resuscitated from an OHCA without ST + randomized (1:1) to either immediate or delayed (48 to 96h) CAG. The primary endpoint of the study is the 180-day survival rate with no or minimal neurological sequel (Cerebral Performance Category (CPC) 1 or 2). The secondary endpoints are: occurrence of shock during the first 48 hours, ventricular tachycardia and/or fibrillation during the first 48 hours, change in left ventricular ejection fraction between baseline and 180 days assessed by echocardiogram, neurological status evaluated by the CPC scale at intensive care unit (ICU) discharge and day 90 neurological status assessed by the Glasgow Outcome Scale Extended score (GOSE) at 90 and 180 days, overall survival rate, and hospital length of stay. Results: 279 patients were enrolled, 141 in the immediate and 138 in the delayed CAG group. Mean age was 65 and 195 were males. The mean delays between randomization and CAG were 0.6 ± 3.7 hours and 55.1 ± 37.2 hours in the immediate and delayed CAG group respectively. The 180-day survival rates among patients with CPC 1 or 2 were 34.1% and 30.7% in the immediate and delayed CAG group, respectively (hazard ratio: 0.87 [95% CI, 0.65; 1.15], P=0.324). The 180-day survival rates in the whole population were 36.2% and 33.3% in the immediate and delayed CAG group, respectively (HR: 0.86 [95% CI, 0.64-1.15], P=0.308). Conclusions: In patients successfully resuscitated after an OHCA without ST +, a strategy of immediate CAG was not found to be better than a strategy of delayed CAG with respect to 180-day survival rate with no or minimal neurological sequel.
Post Hoc Analysis of the Effect of Pegcetacoplan Treatment of Patients with Paroxysmal Nocturnal Hemoglobinuria and Baseline Hemoglobin Levels Greater Than 10 Grams per Deciliter
Authors: Jens Panse, Nicolas Daguindau, Sonia Okuyama Sasaki, Regis Peffault De Latour, Philippe Schafhausen, Nicole Straetmans, Mohammed Al-Adhami, Temitayo Ajayi, Crystal Chen, Michael Yeh, Raymond S Wong
Journal: Blood (2021)
Prediction of Early Mortality with Non-Intensive Acute Myeloid Leukemia (AML) Therapies: Analysis of 1336 Patients from MRC/NCRI and SWOG
Authors: Xu Wang, Ian Thomas, Cono Ariti, Mike Dennis, Priyanka Mehta, Nigel H Russel, Mia Sydenham, Robert Hills, Alan K. Burnett, Sucha Nand, Sarit Assouline, Laura C. Michaelis, Harry P. Erba, Kathleen Kerr, Roland B. Walter, Megan Othus
Journal: Blood (2021)
Efficacy and Safety of Ruxolitinib in the Treatment of Elderly Patients with Policythemia Vera Resistant/Intolerant to Hydroxyurea
Authors: Roberto Latagliata, Daniela Bartoletti, Alessandro Andriani, Massimo Breccia, Elena Rossi, Giuseppe Auteri, Florian H. Heidel, Elena Maria Elli, Novella Pugliese, Francesco Mendicino, Giulia Benevolo, Bruno Martino, Alessandra D'Addio, Alessia Tieghi, Ambra Di Veroli, Gianni Binotto, Monica Crugnola, Massimiliano Bonifacio, Giovanni Caocci, Francesco Cavazzini, Mario Tiribelli, Nicola Vianelli, Michele Cavo, Giuseppe A. Palumbo, Valerio De Stefano, Francesca Palandri
Journal: Blood (2021)
Pathogenesis of Extramedullary Multiple Myeloma: From Resistance to Identification of Novel Therapeutic Targets
Authors: Tomas Jelinek, David Zihala, Tereza Sevcikova, Veronika Kapustova, Hana Sahinbegovic, Anjana Anilkumar Sithara, Tereza Popkova, Hana Plonkova, Lucie Broskevicova, Jan Vrana, Vladimir Zidlik, Martin Havel, Zdenek Koristek, Juli R. Bago, Michal Simicek, Roman Hajek
Journal: Blood (2021)
An in Depth Analysis of Factors Contributing to Diagnostic Delay in Myeloma: A Retrospective UK Study of Patients Journey from Primary Care to Specialist Secondary Care
Authors: Md Imran Hossain, Peter Hampson, Craig Nowell, Shamshad Khan, Ranjoy Sen, Sharadha Sundararaman, Jagdish Adiyodi, Supratik Basu
Journal: Blood (2021)
Evaluation of the BNT162b2 Covid-19 Vaccine in Children 5 to 11 Years of Age
Authors: Emmanuel B Walter, Kawsar R Talaat, Charu Sabharwal, Alejandra Gurtman, Stephen Lockhart, Grant C Paulsen, Elizabeth D Barnett, Flor M Muñoz, Yvonne Maldonado, Barbara A Pahud, Joseph B Domachowske, Eric A F Simões, Uzma N Sarwar, Nicholas Kitchin, Luke Cunliffe, Pablo Rojo, Ernest Kuchar, Mika Rämet, Iona Munjal, John L Perez, Robert W Frenck, Eleni Lagkadinou, Kena A Swanson, Hua Ma, Xia Xu, Kenneth Koury, Susan Mather, Todd J Belanger, David Cooper, Özlem Türeci, Philip R Dormitzer, Uğur Şahin, Kathrin U Jansen, William C Gruber
Journal: New England Journal of Medicine (2021)

Safe, effective vaccines against coronavirus disease 2019 (Covid-19) are urgently needed in children younger than 12 years of age.A phase 1, dose-finding study and an ongoing phase 2-3 randomized trial are being conducted to investigate the safety, immunogenicity, and efficacy of two doses of the BNT162b2 vaccine administered 21 days apart in children 6 months to 11 years of age. We present results for 5-to-11-year-old children. In the phase 2-3 trial, participants were randomly assigned in a 2:1 ratio to receive two doses of either the BNT162b2 vaccine at the dose level identified during the open-label phase 1 study or placebo. Immune responses 1 month after the second dose of BNT162b2 were immunologically bridged to those in 16-to-25-year-olds from the pivotal trial of two 30-μg doses of BNT162b2. Vaccine efficacy against Covid-19 at 7 days or more after the second dose was assessed.During the phase 1 study, a total of 48 children 5 to 11 years of age received 10 μg, 20 μg, or 30 μg of the BNT162b2 vaccine (16 children at each dose level). On the basis of reactogenicity and immunogenicity, a dose level of 10 μg was selected for further study. In the phase 2-3 trial, a total of 2268 children were randomly assigned to receive the BNT162b2 vaccine (1517 children) or placebo (751 children). At data cutoff, the median follow-up was 2.3 months. In the 5-to-11-year-olds, as in other age groups, the BNT162b2 vaccine had a favorable safety profile. No vaccine-related serious adverse events were noted. One month after the second dose, the geometric mean ratio of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralizing titers in 5-to-11-year-olds to those in 16-to-25-year-olds was 1.04 (95% confidence interval [CI], 0.93 to 1.18), a ratio meeting the prespecified immunogenicity success criterion (lower bound of two-sided 95% CI, >0.67; geometric mean ratio point estimate, ≥0.8). Covid-19 with onset 7 days or more after the second dose was reported in three recipients of the BNT162b2 vaccine and in 16 placebo recipients (vaccine efficacy, 90.7%; 95% CI, 67.7 to 98.3).A Covid-19 vaccination regimen consisting of two 10-μg doses of BNT162b2 administered 21 days apart was found to be safe, immunogenic, and efficacious in children 5 to 11 years of age. (Funded by BioNTech and Pfizer; ClinicalTrials.gov number, NCT04816643.).
Sex Differences in Lymphoma Incidence and Excess Mortality By Subtype: A Comprehensive National Study
Authors: Cecilia Radkiewicz, Johanna Borg Bruchfeld, Caroline Weibull, Mats Lambe, Lasse H. Jakobsen, Tarec Christoffer El-Galaly, Karin E. Smedby, Tove Wästerlid
Journal: Blood (2021)
BRUIN CLL-313: A Phase 3 Open-Label, Randomized Study of Pirtobrutinib Versus Bendamustine Plus Rituximab in Untreated Patients with Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (Trial in Progress)
Authors: Wojciech Jurczak, Caroline Dartigeas, Marta Coscia, Peter S. Ganly, Ghassan Al-Jazayrly, Chunxiao Wang, Katherine Bao, Ching Ching Leow, Safi Shahda, Pier Luigi Zinzani
Journal: Blood (2021)
Abstract 9474: Clinical and Epidemiologic Characterization of Infective Endocarditis in a Predominant Hispanic Community of the United States - Mexico Border
Authors: Ezhil Panneerselvam, Jose Cruz Rodriguez, Ruben Montanez, Shristi Nepal, ROHAN DESAI, Kazue Okajima
Journal: Circulation (2021)

Introduction: We aimed to characterize the clinical, epidemiological and echocardiographic features of infective endocarditis (IE) in the United States (US)-Mexico border population. Methods: A retrospective cohort design of all patients with diagnosis of IE in a tertiary university health system in El Paso, Texas. The primary outcome was a composite of death, stroke, other embolic events or heart failure. Patients were risk-stratified using the Simplified Risk Score Calculation (scores &gt;=5 were considered high risk). Kaplan-Meier method was used to evaluate time to outcome which was subsequently compared between groups by Wilcoxon log-rank test and a priori multivariable proportional hazard model. Results: Final analytic sample was 155 patients with a median follow-up of 2.21 years. Prosthetic valve IE composed 10.3% of our patients. The most prevalent organism was S. aureus (35.5%), followed by streptococcus species (20.0%). Echocardiographic features of severe endocarditis (indication of surgery) were present in 123 patients (79.5%). Surgical treatment occurred in 23.2% of patients, and the median time to surgery was 12 days. A total of 53% of patients were in the high-risk score category and these patients were more likely to have a conservative, medical treatment compared to those with a low to intermediate risk score (62.2% vs 37.8%, p&lt;0.01). The composite outcome was met by 47.5% of our cohort. Median time to event was 69 days. In multivariable analysis, factors associated with increased risk of the composite outcome were high-risk score category (HR 2.6, 95%CI 1.6-4.3, p&lt;0.01), Medicaid (HR 3.2, 95%CI 1.6-6.2, p&lt;0.01) and uninsured status (HR 2.3, 95%CI 1.3-4.3, p&lt;0.01). Conclusion: In a predominant Hispanic community of the US-Mexico border, high-risk IE patients were more likely to experience the composite outcome, and less likely to get surgical treatment. In multivariable analysis, uninsured patients had a significant higher risk of readmission, embolic events, heart failure or death.
Abstract 9487: Sildenafil (Viagra) Aggravates the Development of Experimental Abdominal Aortic Aneurysm
Authors: Chongyang Zhang, Amy Mohan, Hangchuan Shi, Chen Yan
Journal: Circulation (2021)

Introduction: PDE5 plays a critical role in vascular smooth muscle cell (SMC) contraction by hydrolyzing 3’,5’ cyclic monophosphate (cGMP) and antagonizing cGMP-dependent protein kinase I (PKGI)-mediated vascular relaxation. SMC contractile dysfunction is implicated in the pathogenesis of aortic aneurysm (AA). PDE5 inhibitors, such as Sildenafil, have been used clinically for treating erectile dysfunction (Viagra) and pulmonary hypertension (Revatio), through promoting SMC relaxation via elevating cGMP. However, it has been reported that PDE5 expression is reduced in human thoracic aneurysms and Viagra usage is associated with human aneurysm rupture or aortic dissection in several case reports. Objective: We aim to investigate the effect of sildenafil in the development of experimental abdominal aortic aneurysm (AAA), the most common form of AA that mainly occurs in elderly male. Methods and Results: AAA was induced in C57BL/6J mouse by periaortic elastase in combination with 3-aminopropionitrile fumarate salt (BAPN) treatment to block elastin/collagen formation. Immunofluorescent staining showed decreased PDE5 expression in mouse AAA. The effect of Sildenafil was examined on pre-existing moderate AAA by providing in drinking water for 28 days. We found that Sildenafil significantly aggravated aneurysmal wall dilation and elastin degradation. Mechanistically, the effect of Sildenafil on the signaling of SMC contraction and PKGI activation were examined in the medial lesion area of AAA. Immunofluorescent staining revealed that Sildenafil significantly decreased the phosphorylation of myosin light chain 2 (MLC2) at Ser19 in AAA, a biochemical marker of SMC contraction. Proximity ligation assay (PLA) revealed an increase of cGMP-PKGI interaction by Sildenafil, an indication of PKGI activation. Conclusions: Chronic Sildenafil treatment aggravated experimental AAA development and elastin degradation by dysregulating contractile signaling in SMCs. Our findings may raise caution of clinical usage of Viagra in aneurysmal patients.
A Phase II, Multicenter, Single-Arm, Open-Label Study of Parsaclisib, a PI3Kδ Inhibitor, in Relapsed or Refractory Follicular Lymphoma in China
Authors: Zhong Zheng, Huilai Zhang, Jingwen Wang, Keshu Zhou, Li Zhang, Hui Zhou, Qingyuan Zhang, Weili Zhao
Journal: Blood (2021)
Targeting PI3K-AKT-mTOR Signaling in Multiple Myeloma Mesenchymal Stem Cells Mediates Antiproliferative Effect on Myeloma Cells
Authors: Luca Heinmann, Helal Mohammed Mohammed Ahmed Noman, Klara Möllers, Subbaiah Chary Nimmagadda, Kaiyan Sun, Daria Frank, Hanna Korab, Lanying Wei, Anja Baumann, Alexandra Poos, Marc-Steffen Raab, Georg Lenz, Cyrus Khandanpour
Journal: Blood (2021)
Single-Cell Transcriptomic Analysis Reveals Loss of Activated Bone Marrow NK Cells in Multiple Myeloma Patients Which Associates with Disease Progression in Mice
Authors: Sabrin Tahri, Zoltan Kellermayer, Madelon M.E. de Jong, Natalie Papazian, Cathelijne Fokkema, Chelsea den Hollander, Pieter van de Woestijne, Mark van Duin, Annemiek Broijl, Pieter Sonneveld, Tom Cupedo
Journal: Blood (2021)