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https://www.readbyqxmd.com/read/28927801/design-synthesis-and-antitumor-activity-of-novel-sorafenib-derivatives-bearing-pyrazole-scaffold
#1
Min Wang, Shan Xu, Huajun Lei, Caolin Wang, Zhen Xiao, Shuang Jia, Jia Zhi, Pengwu Zheng, Wufu Zhu
Four series of Sorafenib derivatives bearing pyrazole scaffold (8a-m, 9a-c, 10a-e and 11a) were synthesized and characterized by NMR and MS. All of the target compounds were evaluated for the cytotoxicity against A549, HepG2, MCF-7, and PC-3 cancer cell lines and some selected compounds were further evaluated for the activity against VEGFR-2/KDR, BRAF, CRAF, c-Met, EGFR and Flt-3 kinases. Compounds 8b and 8i were more active than that of compounds 8h, 9a, especially the IC50 value of compounds 8b on VEGFR-2 kinase was 0...
September 6, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28916904/early-assessment-of-response-to-induction-therapy-in-acute-myeloid-leukemia-using-18-f-flt-pet-ct
#2
Eun Ji Han, Bo-Hee Lee, Jeong-A Kim, Young Ha Park, Woo Hee Choi
BACKGROUND: We evaluated the suitability of (18)F-fluorodeoxythymidine ((18)F-FLT) positron emission tomography (PET)/computed tomography (CT) for assessment of the early response to induction therapy and its value for predicting clinical outcome in patients with acute myeloid leukemia (AML). Adult patients who had histologically confirmed AML and received induction therapy were enrolled. All patients underwent (18)F-FLT PET/CT after completion of induction. PET/CT images were visually and quantitatively assessed...
September 16, 2017: EJNMMI Research
https://www.readbyqxmd.com/read/28915798/vemurafenib-plus-cobimetinib-in-unresectable-stage-iiic-or-stage-iv-melanoma-response-monitoring-and-resistance-prediction-with-positron-emission-tomography-and-tumor-characteristics-reposit-study-protocol-of-a-phase-ii-open-label-multicenter-study
#3
Bernies van der Hiel, John B A G Haanen, Marcel P M Stokkel, Daniel S Peeper, Connie R Jimenez, Jos H Beijnen, Bart A van de Wiel, Ronald Boellaard, Alfons J M van den Eertwegh
BACKGROUND: In patients with BRAFV600 mutated unresectable stage IIIc or metastatic melanoma, molecular targeted therapy with combined BRAF/MEK-inhibitor vemurafenib plus cobimetinib has shown a significantly improved progression-free survival and overall survival compared to treatment with vemurafenib alone. Nevertheless, the majority of BRAFV600 mutation-positive melanoma patients will eventually develop resistance to treatment. Molecular imaging with (18)F-Fluorodeoxyglucose ((18)F-FDG) PET has been used to monitor response to vemurafenib in some BRAFV600 mutated metastatic melanoma patients, showing a rapid decline of (18)F-FDG uptake within 2 weeks following treatment...
September 15, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28893953/fate-decision-between-group-3-innate-lymphoid-and-conventional-nk-cell-lineages-by-notch-signaling-in-human-circulating-hematopoietic-progenitors
#4
Seishi Kyoizumi, Yoshiko Kubo, Junko Kajimura, Kengo Yoshida, Tomonori Hayashi, Kei Nakachi, Malcolm A Moore, Marcel R M van den Brink, Yoichiro Kusunoki
The role of Notch signaling in human innate lymphoid cell (ILC) differentiation is unclear, although IL-7 and IL-15 promote differentiation of natural cytotoxicity receptor (NCR) NKp44(+) group 3 ILCs (NCR(+)ILC3s) and conventional NK (cNK) cells from CD34(+) hematopoietic progenitor cells (HPCs) ex vivo. In this study, we analyzed the functions of Notch in the differentiation of NCR(+)ILC3s and cNK cells from human HPC subpopulations circulating in peripheral blood by limiting dilution and clonal assays using high-throughput flow cytometry...
September 11, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28864183/novel-volumetric-method-for-highly-repeatable-injection-in-microchip-electrophoresis
#5
Noel S Ha, Jimmy Ly, Jason Jones, Shilin Cheung, R Michael van Dam
A novel injector for microchip electrophoresis (MCE) has been designed and evaluated that achieves very high repeatability of injection volume suitable for quantitative analysis. It eliminates the injection biases in electrokinetic injection and the dependence on pressure and sample properties in hydrodynamic injection. The microfluidic injector, made of poly(dimethylsiloxane) (PDMS), operates similarly to an HPLC injection valve. It contains a channel segment (chamber) with a well-defined volume that serves as an "injection loop"...
September 8, 2017: Analytica Chimica Acta
https://www.readbyqxmd.com/read/28853043/comparative-evaluation-of-18-f-flt-and-18-f-fdg-for-detecting-cardiac-and-extra-cardiac-thoracic-involvement-in-patients-with-newly-diagnosed-sarcoidosis
#6
Takashi Norikane, Yuka Yamamoto, Yukito Maeda, Takahisa Noma, Hiroaki Dobashi, Yoshihiro Nishiyama
BACKGROUND: (18)F-FDG PET has been used in sarcoidosis for diagnosis and determination of the extent of the disease. However, assessing inflammatory lesions in cardiac sarcoidosis using (18)F-FDG can be challenging because it accumulates physiologically in normal myocardium. Another radiotracer, 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT), has been investigated as a promising PET tracer for evaluating tumor proliferative activity. In contrast to (18)F-FDG, (18)F-FLT uptake in the normal myocardium is low...
August 29, 2017: EJNMMI Research
https://www.readbyqxmd.com/read/28852983/myocarditis-with-high-18-f-fdg-uptake-and-no-18-f-flt-uptake
#7
Takashi Norikane, Yuka Yamamoto, Takahisa Noma, Yoshihiro Nishiyama
We present a case of myocarditis with increased (18)F-FDG uptake and no (18)F-fluorothymidine (FLT) uptake.
August 29, 2017: Journal of Nuclear Cardiology: Official Publication of the American Society of Nuclear Cardiology
https://www.readbyqxmd.com/read/28828716/concentration-sources-and-risk-assessment-of-pahs-in-bottom-sediments
#8
Agnieszka Baran, Marek Tarnawski, Krzysztof Urbański, Agnieszka Klimkowicz-Pawlas, Iwona Spałek
The aims of the study were to investigate the concentration, sources and ecological risk of PAHs (polycyclic aromatic hydrocarbons) in bottom sediments collected from nine reservoirs located in south-eastern Poland. The concentration of ∑PAHs in sediments ranged from 150 to 33,900 μg kg(-1). The total PAH concentration in the bottom sediments was arranged in the following order: Rybnik > Rzeszów > Brzóza Królewska > Brzóza Stadnicka > Besko > Chechło > Ożanna > Głuchów > Narożniki...
August 21, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/28817576/gestational-diabetes-mellitus-is-associated-with-increased-pro-migratory-activation-of-vascular-endothelial-growth-factor-receptor-2-and-reduced-expression-of-vascular-endothelial-growth-factor-receptor-1
#9
Felipe Troncoso, Jesenia Acurio, Kurt Herlitz, Claudio Aguayo, Patricio Bertoglia, Enrique Guzman-Gutierrez, Marco Loyola, Marcelo Gonzalez, Meriem Rezgaoui, Gernot Desoye, Carlos Escudero
Placentas from gestational diabetes mellitus (GDM) are often hypervascularized; however, participation of vascular endothelial growth factor (VEGF) and its receptors in this placental adaptation is unclear. We aimed to test whether changes in phosphorylation of tyrosine 951 or tyrosine 1175 (pY951 or pY1175) of the vascular endothelial growth factor receptor 2 (KDR) are associated with the proangiogenic state observed in placentas from GDM. We obtained placental samples from women with normal pregnancies (n = 24) or GDM (n = 18)...
2017: PloS One
https://www.readbyqxmd.com/read/28807201/overexpression-of-thioredoxin1-enhances-functional-recovery-in-a-mouse-model-of-hind-limb-ischemia
#10
Inam A Shaikh, Muhammad Tipu Rishi, Mark Youssef, Vaithinathan Selvaraju, Mahesh Thirunavukkarasu, Gopi Ukani, Rajesh Lakshmanan, J Alexander Palesty, Nilanjana Maulik
BACKGROUND: There is keen interest in finding nonsurgical treatments for peripheral vascular disease (PVD). Previously, we demonstrated that selective activation of Thioredoxin1 (Trx1), a 12-kDa cytosolic protein, initiates redox-dependent signaling and promotes neovascularization after ischemic heart disease. Therefore, Trx1 might possess immense potential to not only treat murine hind limb ischemia (HLI) through effective angiogenesis but also provide PVD patients with nonsurgical therapy to enhance neovascularization and improve blood perfusion...
August 2017: Journal of Surgical Research
https://www.readbyqxmd.com/read/28799432/targeted-therapies-in-acute-myeloid-leukemia-a-focus-on-flt-3-inhibitors-and-abt199
#11
Kiran Naqvi, Marina Konopleva, Farhad Ravandi
Acute myeloid leukemia (AML) remains a therapeutic challenge. Despite ongoing research, the standard therapy for AML has not changed significantly in the past four decades. With the identification of cytogenetic and molecular abnormalities, several promising therapeutic agents are currently being investigated. FLT3 mutation is a well-recognized target seen in 30% of the cytogenetically normal AML. More recently, the BCL2 family of anti-apoptotic proteins have also generated great interest as a therapeutic target...
August 21, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28799176/the-molecular-mechanism-behind-resistance-of-the-kinase-flt3-to-the-inhibitor-quizartinib
#12
Ran Friedman
Fms-like tyrosine kinase 3 (FLT3) is a receptor tyrosine kinase that is a drug target for leukaemias. Several potent inhibitors of FLT3 exists, and bind to the inactive form of the enzyme. Unfortunately, resistance due to mutations in the kinase domain of FLT3 limits the therapeutic effects of these inhibitors. As in many other cases, it is not straightforward to explain why certain mutations lead to drug resistance. Extensive fully-atomistic molecular dynamics (MD) simulations of FLT3 were carried out with an inhibited form (FLT-quizartinib complex), a free (apo) form and an active conformation...
August 11, 2017: Proteins
https://www.readbyqxmd.com/read/28795252/ipet-study-an-flt-pet-window-study-to-assess-the-activity-of-the-steroid-sulfatase-inhibitor-irosustat-in-early-breast-cancer
#13
Carlo Palmieri, Richard Szydlo, Marie Miller, Laura Barker, Neva H Patel, Hironobu Sasano, Tara Barwick, Henry Tam, Dimitri Hadjiminas, Jasmin Lee, Abeer Shaaban, Hanna Nicholas, R Charles Coombes, Laura M Kenny
BACKGROUND: Steroid sulfatase (STS) is involved in oestrogen biosynthesis and irosustat is a first generation, irreversible steroid sulfatase inhibitor. A pre-surgical window-of-opportunity study with irosustat was undertaken in estrogen receptor-positive (ER+) breast cancer to assess the effect of irosustat on tumour cell proliferation as measured by 3'-deoxy-3'-[18F] fluorothymidine uptake measured by PET scanning (FLT-PET) and Ki67. METHODS: Postmenopausal women with untreated ER+ early breast cancer were recruited, and imaged with FLT-PET at baseline and after at least 2 weeks treatment with irosustat, 40 mg once daily orally...
August 9, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28790977/micro-and-nano-vesicles-from-first-trimester-human-placentae-carry-flt-1-and-levels-are-increased-in-severe-preeclampsia
#14
Mancy Tong, Qi Chen, Joanna L James, Peter R Stone, Lawrence W Chamley
BACKGROUND/OBJECTIVES: Preeclampsia is a life-threatening hypertensive disease affecting 3-5% of pregnancies. While the pathogenesis of preeclampsia remains unclear, it is known that placenta-derived factors trigger the disease by activating maternal endothelial cells prior to the onset of clinical symptoms. Extracellular vesicles (EVs) of different sizes extruded by the placenta may be one factor. The truncated/secreted form of Flt-1 (sFlt-1) has also been implicated in the pathogenesis of preeclampsia...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28774461/phase-ii-trial-of-bevacizumab-with-dose-dense-paclitaxel-as-first-line-treatment-in-patients-with-advanced-ovarian-cancer
#15
Nicole D Fleming, Robert L Coleman, Celestine Tung, Shannon N Westin, Wei Hu, Yunjie Sun, Priya Bhosale, Mark F Munsell, Anil K Sood
OBJECTIVES: To assess the tolerability and efficacy of bevacizumab with carboplatin and weekly paclitaxel as first-line adjuvant therapy for advanced stage ovarian cancer. METHODS: After IRB approval, this single-institution, phase II study enrolled patients with stage III or IV epithelial ovarian cancer after primary cytoreductive surgery to treatment with carboplatin (AUC 5), weekly paclitaxel (80mg/m2), and bevacizumab (15mg/kg) every 3weeks for at least 6cycles...
October 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28770274/a-pilot-study-for-texture-analysis-of-18-f-fdg-and-18-f-flt-pet-ct-to-predict-tumor-recurrence-of-patients-with-colorectal-cancer-who-received-surgery
#16
Masatoyo Nakajo, Yoriko Kajiya, Atsushi Tani, Megumi Jinguji, Masayuki Nakajo, Masaki Kitazono, Takashi Yoshiura
PURPOSE: This retrospective study was done to examine whether the heterogeneity in primary tumor F-18-fluorodeoxyglucose ((18)F-FDG) and (18)F-3'-fluoro-3'-deoxythymidine ((18)F-FLT) distribution can predict prognosis of patients with colorectal cancer who received surgery. METHODS: The enrolled 32 patients with colorectal cancer underwent both (18)F-FDG- and (18)F-FLT-PET/CT studies before surgery. Clinicopathological factors, stage, SUVmax, SUVmean, metabolic tumor volume (SUV ≥ 2...
August 3, 2017: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/28767400/flt-1-positive-cells-are-cancer-stem-like-cells-in-colorectal-carcinoma
#17
Ye Huang, Yinpeng Huang, Di Liu, Tianyi Wang, Guang Bai
Recent evidence demonstrates an essential role of cancer stem cells (CSCs) in cancer initiation, progression, migration, metastasis as well as chemo-resistance. Nevertheless, identification of CSCs in different cancers has not been succeeded, since such CSCs are typically lack of a specific and unique marker. Therefore, the current strategy is basically using one or several markers to enrich CSCs, or to isolate CSC-like cells. Here, we showed that in clinically obtained colorectal carcinoma (CRC) specimens, Flt-1, the type 1 receptor for vascular endothelial growth factor A, was significantly upregulated...
July 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28702806/efficacy-and-safety-of-nintedanib-plus-docetaxel-in-patients-with-advanced-lung-adenocarcinoma-complementary-and-exploratory-analyses-of-the-phase-iii-lume-lung-1-study
#18
Maya Gottfried, Jaafar Bennouna, Igor Bondarenko, Jean-Yves Douillard, David F Heigener, Maciej Krzakowski, Anders Mellemgaard, Silvia Novello, Sergei Orlov, Yvonne Summers, Joachim von Pawel, Julia Stöhr, Rolf Kaiser, Martin Reck
BACKGROUND: Nintedanib is a triple angiokinase inhibitor approved with docetaxel for adenocarcinoma non-small cell lung cancer after first-line chemotherapy (FLT). In the phase III LUME-Lung 1 study, overall survival (OS) was significantly longer with nintedanib/docetaxel than with placebo/docetaxel in all adenocarcinoma patients and those with time from start of FLT (TSFLT) <9 months. OBJECTIVE: This study sought to extend analyses from the LUME-Lung 1 study, specifically for adenocarcinoma patients, to explore the impact of clinically relevant characteristics on outcomes such as time to progression after FLT...
August 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28700140/development-of-a-molecular-bio-switch-using-fluorescence-lifetime-imaging-incremental-activation-of-fluorescein-diacetate
#19
Eran A Barnoy, Rachela Popovtzer, Dror Fixler
Molecular bio-switches offer an invaluable asset in the shift from systemic to targeted treatments. Within the growing arsenal of switches are imaging probes that functionalize only in given locations or situations. Acetate esters are a common fluorescent example, known to activate upon interaction with esterases. Fluorescein diacetate (FDA) is one such fluorophore used in cell viability assays. These assays rely on the fact that the compound begins colorless and with no fluorescent signature whatsoever, and only after internalization into cells it is possible to detect a fluorescence signal...
July 12, 2017: Journal of Biophotonics
https://www.readbyqxmd.com/read/28695424/flt-pet-for-early-response-evaluation-of-colorectal-cancer-patients-with-liver-metastases-a-prospective-study
#20
Marie Benzon Mogensen, Annika Loft, Marianne Aznar, Thomas Axelsen, Ben Vainer, Kell Osterlind, Andreas Kjaer
BACKGROUND: Fluoro-L-thymidine (FLT) is a positron emission tomography/computed tomography (PET/CT) tracer which reflects proliferative activity in a cancer lesion. The main objective of this prospective explorative study was to evaluate whether FLT-PET can be used for the early evaluation of treatment response in colorectal cancer patients (CRC) with liver metastases. Patients with metastatic CRC having at least one measurable (>1 cm) liver metastasis receiving first-line chemotherapy were included...
December 2017: EJNMMI Research
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