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https://www.readbyqxmd.com/read/27906677/the-implication-of-flt3-amplification-for-flt-targeted-therapeutics-in-solid-tumors
#1
Sung Hee Lim, Sun-Young Kim, Kyung Kim, Hyojin Jang, Soomin Ahn, Kyoung-Mee Kim, Nayoung K D Kim, Woongyang Park, Su Jin Lee, Seung Tae Kim, Se Hoon Park, Joon Oh Park, Young Suk Park, Se-Hoon Lee, Ho Yeong Lim, Keunchil Park, Won Ki Kang, Jeeyun Lee
We investigated the patients with solid cancers harboring Fms-like tyrosine kinase 3 (FLT3) amplification using targeted sequencing of tumor tissue specimen and FISH assay. Simultaneously, FLT3-amplified patient-derived cells (PDCs) were generated to evaluate the sensitivity to FLT3 inhibition. A patient with metastatic colon cancer who was previously treated with more than 3rd line cytotoxic chemotherapy was found to have FLT3 amplification and then received regorafenib showing partial response. In two PDC cell lines with FLT3 amplification, FLT3 mRNA expression was increased, however, the growth of tumor cells was not significantly inhibited by either regorafenib or sorafenib which is known to block the activity FLT3...
November 29, 2016: Oncotarget
https://www.readbyqxmd.com/read/27904694/soluble-flt-1-improves-the-repair-of-ankle-joint-injury-in-rats
#2
Jing Tian, Bing Xie, Liangbi Xiang, Yong Zhao, Dapeng Zhou
The ankle injuries create great pain to a great number of patients worldwide. Past studies have focused on the development of practical treatments to relieve pain and improve recovery, but the molecular mechanisms underlying the ankle injuries, especially the local inflammation in the damaged ankle joint, have been rarely studied. Moreover, although reduction of production and secretion of pro-inflammatory cytokines may reduce the pain and promote the recovery, a practical approach is currently lacking. Here, we detected significantly higher levels of placental growth factor (PLGF) and pro-inflammatory cytokines in the joint fluid from the patients of acute ankle joint injury (AAJI)...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27891549/a-pilot-study-of-the-diagnostic-and-prognostic-values-of-flt-pet-ct-for-pancreatic-cancer-comparison-with-fdg-pet-ct
#3
Masatoyo Nakajo, Yoriko Kajiya, Atsushi Tani, Megumi Jinguji, Masayuki Nakajo, Tohru Nihara, Yoshihiko Fukukura, Takashi Yoshiura
PURPOSE: The purpose of the study was to examine the diagnostic and prognostic values of (18)F-fluorothymidine (FLT)-PET/CT for pancreatic cancer by comparing with (18)F-fluorodeoxyglucose (FDG)-PET/CT. METHODS: Fifteen patients with newly diagnosed pancreatic cancer underwent both FLT and FDG-PET/CT scans before treatment. The sensitivity, specificity, and accuracy in detecting nodal and distant metastases were compared between both scans using McNemar exact or χ (2) test...
November 28, 2016: Abdominal Radiology
https://www.readbyqxmd.com/read/27873232/evidence-based-revised-view-of-the-pathophysiology-of-preeclampsia
#4
Asif Ahmed, Homira Rezai, Sophie Broadway-Stringer
Preeclampsia is a life-threatening vascular disorder of pregnancy due to a failing stressed placenta. Millions of women risk death to give birth each year and globally each year, almost 300,000 lose their life in this process and over 500,000 babies die as a consequence of preeclampsia. Despite decades of research, we lack pharmacological agents to treat it. Maternal endothelial oxidative stress is a central phenomenon responsible for the preeclampsia phenotype of high maternal blood pressure and proteinuria...
November 22, 2016: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/27871461/nuclear-factor-of-activated-t-cells-nfat-regulates-soluble-fms-like-tyrosine-kinase-1-secretion-sflt-1-from-human-placenta
#5
Louie Ye, Amy Gratton, Natalie J Hannan, Ping Cannon, Minh Deo, Kirsten R Palmer, Stephen Tong, Tu'uhevaha J Kaitu'u-Lino, Fiona C Brownfoot
INTRODUCTION: Preeclampsia is a serious complication affecting 5-8% of pregnancies. Central to its pathogenesis is placental hypoxia and inflammation which leads to secretion of soluble fms-like tyrosine kinase 1 (sFlt-1). sFlt-1 causes widespread endothelial dysfunction. The molecular mechanisms regulating sFlt-1 production remain poorly understood. Recently, a binding site for the nuclear factor activated T cells (NFAT) transcription factor has been found on fms-like tyrosine kinase 1 (FLT-1) promoter...
December 2016: Placenta
https://www.readbyqxmd.com/read/27870972/mek-erk-signaling-is-involved-in-the-role-of-vegf-and-igf1-in-cardiomyocyte-differentiation-of-mouse-adipose-tissue-derived-stromal-cells
#6
Chunhui Wang, Wenhui Liu, Xianning Zhang, Yinghui Wang, Huan Liu, Haifang Li
BACKGROUND: We found that mouse brown adipose tissue-derived stromal cells (BATDCs), but not white adipose tissue-derived stromal cells (WATDCs), could spontaneously differentiate into cardiomyocyte-like cells in a simple culture medium. This study would find out some critical trophic factors that were responsible for such difference in differentiation, and further determine the involved signaling pathway. METHODS AND RESULTS: The cardiomyocyte differentiation capacity of cells was identified by morphological observations, immunofluorescence staining, and evaluation of expression of cardiomyocyte specific markers...
November 9, 2016: International Journal of Cardiology
https://www.readbyqxmd.com/read/27854031/evaluation-of-18-f-fluorothymidine-positron-emission-tomography-18-f-flt-pet-ct-methodology-in-assessing-early-response-to-chemotherapy-in-patients-with-gastro-oesophageal-cancer
#7
R Sharma, P Mapelli, G B Hanna, R Goldin, D Power, A Al-Nahhas, S Merchant, R Ramaswami, A Challapalli, T Barwick, E O Aboagye
BACKGROUND: 3'-Deoxy-3'-[(18)F]fluorothymidine ([(18)F]FLT) PET has limited utility in abdominal imaging due to high physiological hepatic uptake of a tracer. We evaluated [(18)F]FLT-PET/CT combined with a temporal-intensity information-based voxel-clustering approach termed kinetic spatial filtering (KSF) to improve tumour visualisation in patients with locally advanced and metastatic gastro-oesophageal cancer and as a marker of early response to chemotherapy. Dynamic [(18)F]FLT-PET/CT data were collected before and 3 weeks post first cycle of chemotherapy...
December 2016: EJNMMI Research
https://www.readbyqxmd.com/read/27817059/-18-f-flt-pet-ct-imaging-in-patients-with-advanced-solid-malignancies-treated-with-axitinib-on-an-intermittent-dosing-regimen
#8
Matthew Scarpelli, Justine Yang Bruce, Lakeesha Carmichael, Jens Eickhoff, Jill Kolesar, Scott Perlman, Robert Jeraj, Glenn Liu
PURPOSE: This study utilizes FLT PET/CT imaging to characterize changes in tumor cell proliferation and vasculature during intermittent treatment with VEGR-TKI axitinib. METHODS: Patients with metastatic solid malignancies underwent 3-week treatment cycles with axitinib (7 and 5 mg BID for safety and pharmacodynamic cohorts, respectively). Cycles consisted of 2 weeks of treatment (dosing period) followed by a 1-week treatment break (washout period). Patients in the pharmacodynamic cohort had up to six FLT PET/CT scans (three scans in each cycle 1 and cycle 3) and had plasma VEGF concentrations measured at imaging timepoints...
November 5, 2016: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/27798786/response-monitoring-with-18-f-flt-pet-and-diffusion-weighted-mri-after-cytotoxic-5-fu-treatment-in-an-experimental-rat-model-for-colorectal-liver-metastases
#9
Sandra Heskamp, Linda Heijmen, Danny Gerrits, Janneke D M Molkenboer-Kuenen, Edwin G W Ter Voert, Kathrin Heinzmann, Davina J Honess, Donna-Michelle Smith, John R Griffiths, Sabrina Doblas, Ralph Sinkus, Peter Laverman, Wim J G Oyen, Arend Heerschap, Otto C Boerman
PURPOSE: The aim of the study was to investigate the potential of diffusion-weighted magnetic resonance imaging (DW-MRI) and 3'-dexoy-3'-[(18)F]fluorothymidine ([(18)F]FLT) positron emission tomography (PET) as early biomarkers of treatment response of 5-fluorouracil (5-FU) in a syngeneic rat model of colorectal cancer liver metastases. PROCEDURES: Wag/Rij rats with intrahepatic syngeneic CC531 tumors were treated with 5-FU (15, 30, or 60 mg/kg in weekly intervals)...
October 31, 2016: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
https://www.readbyqxmd.com/read/27784748/gemcitabine-mechanism-of-action-confounds-early-assessment-of-treatment-response-by-3-deoxy-3-18f-fluorothymidine-in-preclinical-models-of-lung-cancer
#10
Sonja Schelhaas, Annelena Held, Lydia Wachsmuth, Sven Hermann, Davina J Honess, Kathrin Heinzmann, Donna-Michelle Smith, John R Griffiths, Cornelius Faber, Andreas H Jacobs
3'-Deoxy-3'-[(18)F]fluorothymidine positron emission tomography ([(18)F]FLT PET) and diffusion weighted magnetic resonance imaging (DW-MRI) are promising approaches to monitor tumor therapy response. Here, we employed these two imaging modalities to evaluate the response of lung carcinoma xenografts in mice after gemcitabine therapy. Caliper measurements revealed that H1975 xenografts responded to gemcitabine treatment, whereas A549 growth was not affected. In both tumor models uptake of [(18)F]FLT was significantly reduced 6 h after drug administration...
October 26, 2016: Cancer Research
https://www.readbyqxmd.com/read/27784630/minimally-invasive-biomarkers-of-general-anesthetic-induced-developmental-neurotoxicity
#11
X Zhang, F Liu, W Slikker, C Wang, M G Paule
The association of general anesthesia with developmental neurotoxicity, while nearly impossible to study in pediatric populations, is clearly demonstrable in a variety of animal models from rodents to nonhuman primates. Nearly all general anesthetics tested have been shown to cause abnormal brain cell death in animals when administered during periods of rapid brain growth. The ability to repeatedly assess in the same subjects adverse effects induced by general anesthetics provides significant power to address the time course of important events associated with exposures...
October 23, 2016: Neurotoxicology and Teratology
https://www.readbyqxmd.com/read/27784367/-manifestations-of-pet-ct-imaging-in-primary-central-nervous-system-lymphoma
#12
Liang Yin, Zhi-Chun Lin, Jian-Lan Yue, Shi-Ming Huang, Wei Chen
OBJECTIVE: To investigate the PET/CT features of primary central nervous system lymphoma(PCNSL). METHODS: A retrospective analysis of PET/CT imaging manifestations and clinical data was performed in 4 PCNSL cases which were confirmed by surgery or stereotactic pathologic biopsy. RESULTS: The pathologic biopsy in 4 patients all showed diffuse large B cell lymphoma with a total of 8 lesions. All cases were performed with (18)F-FDG PET/CT imaging except 1 patient simultaneously with (18)F-FLT PET/CT imaging in the brain...
October 2016: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/27778036/-biological-characteristics-of-mesenchymal-stem-cell-and-hematopoietic-stem-cell-in-the-co-culture-system
#13
Wei Wei, Chao Xu, Zhi-Yong Ye, Xiao-Jun Huang, Jia-En Yuan, Tian-Bao Ma, Han-Biao Lin, Xiu-Qiong Chen
The aim of the present study was to obtain the qualified hematopoietic stem/progenitor cells (HSC/HPC) and human umbilical cord-mesenchymal stem cells (MSC) in vitro in the co-culture system. Cord blood mononuclear cells were separated from umbilical cord blood by Ficoll lymphocyte separation medium, and then CD34(+) HSC was collected by MACS immunomagnetic beads. The selected CD34(+) HSC/HPC and MSC were transferred into culture flask. IMDM culture medium with 15% AB-type cord plasma supplemented with interleukin-3 (IL-3), IL-6, thrombopoietin (TPO), stem cell factor (SCF) and FMS-like tyrosine kinase 3 ligand (Flt-3L) factors were used as the co-culture system for the amplification of HSC/HPC and MSC...
October 25, 2016: Sheng Li Xue Bao: [Acta Physiologica Sinica]
https://www.readbyqxmd.com/read/27774782/reference-independent-wide-field%C3%A2-fluorescence-lifetime-measurements-using-frequency-domain-fd-technique-based-on-phase-and-amplitude-crossing-point
#14
Gilad Yahav, Eran Barnoy, Nir Roth, Lior Turgeman, Dror Fixler
Fluorescence lifetime imaging microscopy (FLIM) is an essential tool in many scientific fields such as biology and medicine thanks to the known advantages of the fluorescence lifetime (FLT) over the classical fluorescence intensity (FI). However, the frequency domain (FD) FLIM technique suffers from its strong dependence on the reference and its compliance to the sample. In this paper, we suggest a new way to calculate the FLT by using the crossing point (CRPO) between the modulation and phase FLTs measured over several light emitting diode (LED) DC currents values instead of either method alone...
October 24, 2016: Journal of Biophotonics
https://www.readbyqxmd.com/read/27770160/current-clinical-status-of-18-f-flt-pet-or-pet-ct-in-digestive-and-abdominal-organ-oncology
#15
Masatoyo Nakajo, Yoriko Kajiya, Megumi Jinguji, Yoshiaki Nakabeppu, Masayuki Nakajo, Tohru Nihara, Takashi Yoshiura
Positron emission tomography (PET) or PET/computed tomography (CT) using (18)F-3'-fluoro-3'-deoxythymidine ((18)F-FLT) offers noninvasive assessment of cell proliferation in human cancers in vivo. The present review discusses the current status on clinical applications of (18)F-FLT-PET (or PET/CT) in digestive and abdominal oncology by comparing with (18)F-fluorodeoxyglucose ((18)F-FDG)-PET (or PET/CT). The results of this review show that although (18)F-FLT uptake is lower in most cases of digestive and abdominal malignancies compared with (18)F-FDG uptake, (18)F-FLT-PET can be used to detect primary tumors...
October 21, 2016: Abdominal Radiology
https://www.readbyqxmd.com/read/27758693/assessment-of-poly-vinyl-alcohol-coated-flutamide-nanoparticulates-and-their-efficacy-on-prostate-cancer-cells
#16
R S Surenya, K S Snima, V Nair Shantikumar, Vinoth Kumar Lakshmanan
Flutamide (FLT) is a non steroidal antiandrogenic drug used to treat prostate cancer. Its poor aqueous solubility and toxicity are the major hindrance for oral drug delivery. The nanoformulation of flutamide increases its aqueous solubility thereby improves the therapeutic efficacy of the chemodrug. Poly (vinyl alcohol) (PVA) coated flutamide nanoparticles (PVA FLT NPs) were formulated by nanoprecipitation method and characterized by DLS, TEM and FTIR. The nanoparticles were about 300nm size and spherical in shape...
October 18, 2016: Current Drug Delivery
https://www.readbyqxmd.com/read/27751419/outcome-of-twin-twin-transfusion-syndrome-treated-by-laser-therapy-in-taiwan-s-single-center-role-of-quintero-staging-system
#17
Yao-Lung Chang, An-Shine Chao, Shuenn-Dyh Chang, Peter Cc Hsieh, Sheng-Yuan Su, Kuan-Ju Chen, Po-Jen Cheng, Tzu-Hao Wang
OBJECTIVE: To evaluate the outcome of twin-twin transfusion syndrome (TTTS) treated by fetoscopic laser therapy (FLT) stratified by Quintero staging. MATERIALS AND METHODS: A total of 100 TTTS cases treated by FLT, from October 2005 to August 2014, were included in this study. Cases were divided into first and second half periods to evaluate the learning effect-related outcomes, and logistic regression was applied to determine the independent factors in predicting the perinatal outcomes...
October 2016: Taiwanese Journal of Obstetrics & Gynecology
https://www.readbyqxmd.com/read/27751167/effects-of-capecitabine-treatment-on-the-uptake-of-thymidine-analogs-using-exploratory-pet-imaging-agents-18-f-fau-18-f-fmau-and-18-f-flt
#18
Christopher I McHugh, Jawana M Lawhorn-Crews, Dipenkumar Modi, Kirk A Douglas, Steven K Jones, Thomas J Mangner, Jerry M Collins, Anthony F Shields
BACKGROUND: A principal goal for the use of positron emission tomography (PET) in oncology is for real-time evaluation of tumor response to chemotherapy. Given that many contemporary anti-neoplastic agents function by impairing cellular proliferation, it is of interest to develop imaging modalities to monitor these pathways. Here we examined the effect of capecitabine on the uptake of thymidine analogs used with PET: 3'-deoxy-3'-[(18)F]fluorothymidine ((18)F-FLT), 1-(2'-deoxy-2'-[(18)F]fluoro-β-D-arabinofuranosyl) thymidine ((18)F-FMAU), and 1-(2'-deoxy-2'-[(18)F]fluoro-β-D-arabinofuranosyl) uracil ((18)F-FAU) in patients with advanced cancer...
October 17, 2016: Cancer Imaging: the Official Publication of the International Cancer Imaging Society
https://www.readbyqxmd.com/read/27743086/bp-1t-an-antiangiogenic-benzophenone-thiazole-pharmacophore-counteracts-hif-1-signalling-through-p53-mdm2-mediated-hif-1%C3%AE-proteasomal-degradation
#19
Prabhu Thirusangu, V Vigneshwaran, T Prashanth, B R Vijay Avin, Vikas H Malojirao, H Rakesh, Shaukath Ara Khanum, Riaz Mahmood, B T Prabhakar
Hypoxia is a feature of all solid tumours, contributing to tumour progression. Activation of HIF-1α plays a critical role in promoting tumour angiogenesis and metastasis. Since its expression is positively correlated with poor prognosis for cancer patients, HIF-1α is one of the most convincing anticancer targets. BP-1T is a novel antiproliferative agent with promising antiangiogenic effects. In the present study, the molecular mechanism underlying cytotoxic/antiangiogenic effects of BP-1T on tumour/non-tumour angiogenesis was evaluated...
October 14, 2016: Angiogenesis
https://www.readbyqxmd.com/read/27737805/differentiation-of-nerve-derived-adult-pluripotent-stem-cells-into-osteoblastic-and-endothelial-cells
#20
Shang-You Yang, Nora Strong, Xuan Gong, Michael H Heggeness
BACKGROUND: Stem cell-involved tissue engineering has gained dramatic attention as a therapeutic strategy for tissue regeneration including bone repair. However, the currently available possibilities to use embryonic stem cells and induced pluripotent stem cells (iPCs) face potential ethical issues, as well as risks of malignant transformation and immune rejection. Recently identified peripheral nerve-derived adult pluripotent cells (NEDAPS) that quickly proliferate after exposure to BMP-2 or nerve trauma and exhibit many embryonic stem cell characteristics may provide an attractive source cells for a variety of regenerative therapies...
October 10, 2016: Spine Journal: Official Journal of the North American Spine Society
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