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Author: Grafiati
Published: 9 March 2023
Last updated: 10 March 2023

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1

Galimberti, C., M. Montagna, T. Piepoli, O. Letari, G. Caselli, R. Artusi, M. Colovic, S. Persiani, and L. C. Rovati. "P11.24 CR13626, an oral tyrosine kinase inhibitor crossing the blood brain barrier, reduces tumour growth and prolongs survival in a mouse model of glioblastoma." Neuro-Oncology 21, Supplement_3 (August 2019): iii47—iii48. http://dx.doi.org/10.1093/neuonc/noz126.170.

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Abstract BACKGROUND Glioblastoma multiforme (GBM) is the most malignant primary brain cancer. Several mutations and alterations of key cellular pathways including tyrosine kinases (TKs) are involved in GBM etiopathogenesis. Currently there is no cure for GBM. Tumour heterogeneity and the presence of the blood brain barrier (BBB), with efflux transporters, are some of the causes of failure of novel therapeutic agents. Thus, appropriate target selectivity and pharmacokinetics (including brain penetration) are critical issues for the generation of potential drug candidates. The main in-vitro and in-vivo properties and antitumour activity of CR13626, a novel brain penetrant TK inhibitor, are presented. MATERIAL AND METHODS CR13626 inhibitory activity against a panel of 173 kinases was assessed. The effect on cellular proliferation was verified in different 2D human glioblastoma cell lines (U87MG, U373, U87MG vIII) and in a U87MG 3D spheroid model by ViaCount assays. The in-vivo antitumour activity was determined in a mouse model of glioblastoma based on the orthotopic injection of U87MG-Luciferase GBM cells in nude mice: oral treatment started on day 9 post-implantation and continued for 10 days (50 mg/kg/daily). Tumour progression was evaluated through the measurement of bioluminescence (BLI) at the end of dosing (day 19) and during follow-up (day 26–33). Survival was also monitored. The pharmacokinetics and brain exposure of CR13626 were assessed by LC/MS/MS in plasma and brain homogenate tissues of CD1 and tumour-bearing nude mice. RESULTS CR13626 potently inhibited FYN, YES, KDR and EGFR kinases, relevant for GBM development, with IC50 values of 69 nM, 3.6 nM, 82 nM and 6 nM, respectively. The compound reduced the proliferation of different human glioblastoma cell lines (GI50 1–3 µM). In CD1 mice, CR13626 had a good oral bioavailability (72%) and brain penetration (brain/plasma ratio of 1.4). In-vivo BLI analysis indicated a time-dependent reduction of tumour growth, reaching 60% on the last BLI evaluation 33 days post-implantation (i.e. 15 days after the end of dosing). Tumour growth inhibition translated into an increase of 25% of the median survival time of animals treated with CR13626 compared to the vehicle group (p<0.05). The observed antitumour effects agreed with the exposure of tumour-bearing mice to CR13626, which was above the TKs in-vitro IC50 values. CONCLUSION The combined abilities of CR13626 to inhibit the activity of TKs involved in GBM development, to cross the BBB, and to reduce tumour growth in-vivo leading to increased survival, warrant its further development as a drug candidate in GBM.
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2

Khatab, Yacoub, Sayed Reshad Ghafouri, Haider Alkhateeb, Debabrata Mukherjee, Hernando Garcia, and Nils Patrick Nickel. "The Association of N-Terminal Pro-Brain Natriuretic Peptide With Time to Clinical Worsening in Hispanic Patients With Pulmonary Arterial Hypertension." Cardiology Research 13, no. 2 (April 2022): 73–80. http://dx.doi.org/10.14740/cr1362.

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3

Chaulin, Aleksey Michailovich, and Artem Konstantinovich Sergeev. "The Role of Fine Particles (PM 2.5) in the Genesis of Atherosclerosis and Myocardial Damage: Emphasis on Clinical and Epidemiological Data, and Pathophysiological Mechanisms." Cardiology Research 13, no. 5 (October 2022): 268–82. http://dx.doi.org/10.14740/cr1366.

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4

Doctor, Pezad, William A. Scott, Kaitlin Tindel, and Hoang H. Nguyen. "Ivabradine Overdose in a Newborn: Precautions of Dispensing in Infants." Cardiology Research 13, no. 4 (August 2022): 242–45. http://dx.doi.org/10.14740/cr1392.

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5

Livesay, James, Benjamin Fogelson, Hassan Tahir, and Raj Baljepally. "Comparison of Tricuspid Regurgitation Severity Between Cardiac Resynchronization Therapy Versus Right Ventricular Pacing in Patients With Chronic Obstructive Pulmonary Disease." Cardiology Research 13, no. 3 (June 2022): 128–34. http://dx.doi.org/10.14740/cr1365.

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6

Safonova, Julia, Maria Kozhevnikova, Yulia Danilogorskaya, Elena Zheleznykh, Vita Zektser, Irina Ilgisonis, Lyudmila Popova, Natalia Khabarova, Elena Privalova, and Yuri Belenkov. "Angiotensin-Converting Enzyme Inhibitor Therapy Effects in Patients With Heart Failure With Preserved and Mid-Range Ejection Fraction." Cardiology Research 12, no. 6 (December 2021): 363–68. http://dx.doi.org/10.14740/cr1322.

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7

Abney, Lon, Tyler Coombes, Laylan Shali, Jared Spoons, and W. Jeremy Mahlow. "Rate of Recovery of Left Ventricular Ejection Fraction in a Real-World Population of Patients Receiving a Wearable Cardioverter Defibrillator." Cardiology Research 12, no. 6 (December 2021): 340–43. http://dx.doi.org/10.14740/cr1325.

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8

Ahmad, Hoda Abdolmonem, Dixon Thomas, Maryam Alrais, Aaron Burton, and Rajaram Jagdale. "Shortcoming of Measuring Patient Satisfaction’s Association With Anemia-Based Cardiovascular Risk in End-Stage Kidney Disease Patients." Cardiology Research 12, no. 6 (December 2021): 344–50. http://dx.doi.org/10.14740/cr1332.

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9

Schloss, Brian, Ismail Bekiroglu, Colin O’Connor, Simon Lee, Julie Rice, Stephani S. Kim, and Joseph D. Tobias. "Hemodynamic and Respiratory Effects of Regadenoson During Radiologic Imaging in Infants and Children." Cardiology Research 12, no. 6 (December 2021): 329–34. http://dx.doi.org/10.14740/cr1323.

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10

Arshad, Samiullah, George A. Davis, Muhammad Amir, Ythan H. Goldberg, Vedant A. Gupta, Ahmed K. Abdel-Latif, and Susan Smyth. "Trends and Outcomes of Oral Anticoagulation With Direct Current Cardioversion for Atrial Fibrillation/Flutter at an Academic Medical Center." Cardiology Research 13, no. 2 (April 2022): 88–96. http://dx.doi.org/10.14740/cr1352.

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11

Thakker, Ravi A., Rafic F. Berbarie, Paul Kumfa, and Syed Gilani. "Snaring Technique for Removal of Entrapped Coronary Guidewire in the Left Anterior Descending Artery." Cardiology Research 13, no. 2 (April 2022): 118–21. http://dx.doi.org/10.14740/cr1369.

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12

Kewcharoen, Jakrin, Andrew K. Chang, Purvi Parwani, Gary Fraser, Aditya Bharadwaj, Ahmed Seliem, Diane Tran, Liset Stoletniy, Antoine Sakr, and Dmitry Abramov. "Echocardiographic Parameters and Outcomes in Methamphetamine-Associated Heart Failure: A Propensity Score-Weighted Analysis." Cardiology Research 13, no. 2 (April 2022): 81–87. http://dx.doi.org/10.14740/cr1364.

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13

Papadis, Athanasios, Stefano Svab, Nicolas Brugger, Jonas Lanz, Robert von Arx, Konstantinos Stamou, and Stefanos Sakellaropoulos. "“Broken Heart” and “Broken Brain”: Which Connection?" Cardiology Research 13, no. 1 (February 2022): 65–70. http://dx.doi.org/10.14740/cr1336.

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14

Munlemvo, Dolly M., Joseph D. Tobias, Kristin M. Chenault, and Aymen Naguib. "Prothrombin Complex Concentrates to Treat Coagulation Disturbances: An Overview With a Focus on Use in Infants and Children." Cardiology Research 13, no. 1 (February 2022): 18–26. http://dx.doi.org/10.14740/cr1342.

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15

Somberg, John. "Heart Failure Research and Polypharmacy." Cardiology Research 13, no. 1 (February 2022): 1. http://dx.doi.org/10.14740/cr1356.

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16

Saitoh, Masakazu, Tetsuya Takahashi, Tomoyuki Morisawa, Akio Honzawa, Miho Yokoyama, Abidan Abulimiti, Nobuyuki Kagiyama, et al. "Remote Cardiac Rehabilitation in Older Cardiac Disease: A Randomized Case Series Feasibility Study." Cardiology Research 13, no. 1 (February 2022): 57–64. http://dx.doi.org/10.14740/cr1346.

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17

Nik Mohamed Kamal, Nik Mohamed Firdaus, Nasibah Mohamad, and Bazli Md Yusoff. "Dizziness and syncope after subclavian steal: A case report of a rarely symptomatic, common vascular disorder." Malaysian Family Physician 17, no. 1 (March 15, 2022): 82–85. http://dx.doi.org/10.51866/cr1306.

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Subclavian steal syndrome (SSS) is a manifestation of vertebrobasilar artery insufficiency due to stenosis of the proximal subclavian artery. It is a common vascular disorder; however, most patients are asymptomatic, and the disorder is commonly found incidentally during imaging. Nevertheless, some patients may present with arm ischemia or signs and symptoms of vertebrobasilar insufficiency, such as vertigo, dizziness, diplopia, ataxia, dysarthria, and syncopal episodes. We present a case of a male patient who presented with sudden onset dizziness, syncopal episodes, and blood pressure discrepancy between his arms. Diagnosis was a challenge, and the patient underwent several investigations, including basic bloodwork, electrocardiography (ECG), echocardiography, brain computed tomography (CT), and coronary CT angiography (CTA). Narrowing in the proximal left subclavian artery was found during coronary CTA, which confirmed the diagnosis of SSS.
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18

Takara, Yuki, Masakazu Saitoh, Tomoyuki Morisawa, Tetsuya Takahashi, Nozomu Yoshida, Munetoshi Sakiyama, Ryuta Nakamura, Imun Tei, and Toshiyuki Fujiwara. "Clinical Characteristics of Older Heart Failure Patients With Hospital-Acquired Disability: A Preliminary, Single-Center, Observational Study." Cardiology Research 12, no. 5 (October 2021): 293–301. http://dx.doi.org/10.14740/cr1306.

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19

Somberg, John. "Do We Serve a Need?" Cardiology Research 12, no. 5 (October 2021): 269. http://dx.doi.org/10.14740/cr1324.

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20

Wong, Rebecca Pei Ying, and Philip George. "Covid-19, not your normal flu: A case report on Covid-19 psychosis and mania in a Malaysian hospital." Malaysian Family Physician 17, no. 3 (August 2, 2022): 144–48. http://dx.doi.org/10.51866/cr1369.

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Evidence suggests that acute severe coronavirus disease 2019 (COVID-19) may be associated with neuropsychiatric symptoms. This is a case report of a patient who had recently been infected with COVID-19 and had no history of psychiatric disorders presenting a few days after inpatient discharge from COVID-19 treatment with acute onset of psychosis and manic symptoms. This case illustrates the psychiatric presentation, possible causes, and management of post-COVID-19 psychosis.
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21

May, André, Ronaldo Da Silva Viana, Michelli De Souza Dos Santos, and Evandro Henrique Figueiredo Moura Da Silva. "Aplicação de glyphosate na dessecação do sorgo biomassa." Revista Brasileira de Herbicidas 15, no. 4 (December 10, 2016): 362. http://dx.doi.org/10.7824/rbh.v15i4.487.

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O sorgo biomassa é uma alternativa para a geração de energia renovável pela queima em caldeiras, destacando-se por sua alta produtividade e possibilidade de mecanização de todos os seus processos agrícolas. Uma alternativa comum para a redução da umidade de culturas é a aplicação de herbicidas dessecantes, contudo, não há pesquisas que elucidem a perda de umidade da massa colhida de sorgo com a aplicação de dessecantes na parte aérea, antes da colheita. Assim, o objetivo deste trabalho foi avaliar aplicação de glyphosate na dessecação do sorgo. O delineamento experimental utilizado foi em blocos inteiramente casualizados, no esquema fatorial 2x5x4, constituídos por: duas cultivares de sorgo (BRS 716 e CR 1342); cinco doses de glyphosate (0, 720, 1.440, 2.160 e 2.880 g ingrediente ativo ha-1) e quatro épocas de coleta das plantas (7, 14, 21 e 28 dias após a aplicação), com 4 repetições. Durante as diferentes épocas de coleta das plantas foram realizadas as avaliações da biomassa fresca e seca dos colmos e folhas e porcentagem de biomassa seca dos colmos e das folhas. A aplicação do glyphosate não foi eficaz no processo de dessecação das plantas de sorgo biomassa BRS 716 e CR1342.
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