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https://www.readbyqxmd.com/read/28340283/comparative-analysis-of-pulmonary-hypertension-in-patients-treated-with-imatinib-nilotinib-and-dasatinib
#1
Mariko Minami, Takeshi Arita, Hiromi Iwasaki, Tsuyoshi Muta, Takatoshi Aoki, Kenichi Aoki, Satoshi Yamasaki, Takamitsu Matsushima, Koji Kato, Katsuto Takenaka, Kazuki Tanimoto, Tomohiko Kamimura, Ryosuke Ogawa, Koichi Akashi, Toshihiro Miyamoto
Pulmonary hypertension (PH) is a rare, but life-threatening, adverse event in patients treated with tyrosine kinase inhibitors (TKIs), such as dasatinib, but has not been fully evaluated in patients treated with imatinib or nilotinib. We used echocardiography to noninvasively assess the incidence of PH in 105 patients with chronic myeloid leukaemia (CML) treated with imatinib (n = 37), nilotinib (n = 30) or dasatinib (n = 38). The mean triscupid regurgitation peak gradient (TRPG), which reflects pulmonary arterial pressure, was 22·7 mmHg in the imatinib group, 23·1 mmHg in the nilotinib group and 23·4 mmHg for dasatinib group...
March 24, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28339780/adverse-kidney-effects-of-epidermal-growth-factor-receptor-inhibitors
#2
Hassan Izzedine, Mark A Perazella
The epidermal growth factor receptor (EGFR) is implicated in various malignancies. The past decade has seen the development and widespread use of EGFR inhibitors for the successful treatment of such cancers. Available EGFR inhibitors include small molecule tyrosine-kinase inhibitors and monoclonal antibodies. Class-related renal adverse events result in dual toxicity including tubular/electrolyte disorders and glomerulopathies. Tubular injury is common and mainly due to monoclonal antibodies while glomerulopathy is rare and related to various anti-EGFR agents...
February 23, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28339693/neuronal-signaling-repertoire-in-the-mammalian-sperm-functionality
#3
Alfredo Ramírez-Reveco, Franz Villarroel-Espíndola, Joan E Rodríguez-Gil, Ilona I Concha
The common embryonic origin has been a recurrent explanation to understand the presence of "neural receptors" in sperm. However, this designation has conditioned a bias marked by the classical neurotransmission model, dismissing the possibility that neurotransmitters can play specific roles in the sperm function by themselves. For instance, the launching of acrosome reaction, a fundamental sperm function, includes several steps that recall the process of presynaptic secretion. Unlike of postsynaptic neuron, whose activation is mediated by molecular interaction between neurotransmitter and postsynaptic receptors, the oocyte activation is not mediated by receptors, but by cytosolic translocation of sperm phospholipase (PLCζ)...
February 20, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/28339691/z-guggulsterone-produces-antidepressant-like-effects-in-mice-through-activation-of-the-bdnf-signaling-pathway
#4
Chao Huang, Wen-Feng Hu, Ji-Li Wang, Peng Wang, Yu Gong, Li-Juan Tong, Bo Jiang, Wei Zhang, Yi-Bin Qin, Zhuo Chen, Rong-Rong Yang
Background: Z-guggulsterone, an active compound extracted from the gum resin of the tree commiphora mukul, has been shown to improve animal memory deficits via activating the brain-derived neurotrophic factor (BDNF) signaling pathway. Here, we investigated the antidepressant-like effect of Z-guggulsterone in a chronic unpredictable stress (CUS) mouse model of depression. Methods: The effects of Z-guggulsterone were assessed in mice tail suspension test (TST), forced swimming test (FST)...
February 21, 2017: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28339658/acute-cell-volume-regulation-by-janus-kinase-2-mediated-sodium-hydrogen-exchange-activation-develops-at-the-late-one-cell-stage-in-mouse-preimplantation-embryos%C3%A2
#5
Baozeng Xu, Chenxi Zhou, Megan Meredith, Jay M Baltz
Early preimplantation embryos are extremely sensitive to dysregulation of cell volume, which can lead to developmental arrest. It was previously shown that mouse embryos at the two-cell stage respond to a cell volume decrease by quickly activating Na+/H+ exchange via a signaling mechanism that involves the tyrosine kinase Janus kinase 2 (JAK2). However, it was not known whether this mechanism is active at the one-cell stage, when embryos are most sensitive to perturbed cell volume. Na+/H+ exchanger activity elicited by an induced cell volume decrease was significantly lower at the mid one-cell stage than at the late one-cell stage or during the two-cell stage...
February 17, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/28339163/next-generation-sequencing-of-urine-specimens-a-novel-platform-for-genomic-analysis-in-patients-with-non-muscle-invasive-urothelial-carcinoma-treated-with-bacille-calmette-gu%C3%A3-rin
#6
Sasinya N Scott, Irina Ostrovnaya, Caroline M Lin, Nancy Bouvier, Bernard H Bochner, Gopakumar Iyer, David Solit, Michael F Berger, Oscar Lin
BACKGROUND: Biopsies from patients with high-risk (HR) non-muscle-invasive urothelial carcinoma (NMIUC), especially flat urothelial carcinoma in situ, frequently contain scant diagnostic material or denuded mucosa only, and this precludes further extensive genomic analysis. This study evaluated the use of next-generation sequencing (NGS) analysis of urine cytology material from patients with HR NMIUC in an attempt to identify genetic alterations that might correlate with clinical features and responses to bacille Calmette-Guérin (BCG) treatment...
March 24, 2017: Cancer
https://www.readbyqxmd.com/read/28339142/selective-effects-of-oral-anti-angiogenic-tyrosine-kinase-inhibitors-on-an-animal-model-of-hereditary-hemorrhagic-telangiectasia
#7
Yong Hwan Kim, Mi-Jung Kim, Se-Woon Choe, Dennis Sprecher, Young Jae Lee, S Paul Oh
BACKGROUND: Epistaxis and gastrointestinal (GI) tract hemorrhages are common symptoms of aged hereditary hemorrhagic telangiectasia (HHT) patients that result in anemia. Clinical as well as animal studies have suggested that vascular endothelial growth factor (VEGF) neutralizing antibodies lessen hemorrhage associated with adult onset arteriovenous malformations (AVMs). OBJECTIVES: The goal of this study is to evaluate potential therapeutic effects of oral delivery of four anti-angiogenic tyrosine-kinase inhibitors (TKIs) in the development of adult onset AVMs in a murine model of HHT...
March 24, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28339027/su6668-modulates-prostate-cancer-progression-by-downregulating-mtdh-akt-signaling-pathway
#8
Benjiang Qian, Yi Yao, Changming Liu, Jiabing Zhang, Huihong Chen, Huizhang Li
Prostate cancer is the second leading cause of cancer deaths among men in Western counties and has increased in incidence also in China in recent years. Although diagnosis modalities for primary prostate cancer have markedly improved, there are still no effective therapies for metastatic prostate cancer. SU6668 is an inhibitor of the tyrosine kinase activity of three angiogenic receptors VEGFR2, PDGFRβ and FGFR1. There is strong experimental evidence that SU6668 can induce growth inhibition of various primary tumors...
March 22, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28338656/focal-adhesion-kinase-depletion-reduces-human-hepatocellular-carcinoma-growth-by-repressing-enhancer-of-zeste-homolog-2
#9
Daniela Gnani, Ilaria Romito, Simona Artuso, Marco Chierici, Cristiano De Stefanis, Nadia Panera, Annalisa Crudele, Sara Ceccarelli, Elena Carcarino, Valentina D'Oria, Manuela Porru, Ezio Giorda, Karin Ferrari, Luca Miele, Erica Villa, Clara Balsano, Diego Pasini, Cesare Furlanello, Franco Locatelli, Valerio Nobili, Rossella Rota, Carlo Leonetti, Anna Alisi
Hepatocellular carcinoma (HCC) is the most common type of liver cancer in humans. The focal adhesion tyrosine kinase (FAK) is often over-expressed in human HCC and FAK inhibition may reduce HCC cell invasiveness. However, the anti-oncogenic effect of FAK knockdown in HCC cells remains to be clarified. We found that FAK depletion in HCC cells reduced in vitro and in vivo tumorigenicity, by inducing G2/M arrest and apoptosis, decreasing anchorage-independent growth, and modulating the expression of several cancer-related genes...
March 24, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28338646/type-iv-secretion-and-signal-transduction-of-helicobacter-pylori-caga-through-interactions-with-host-cell-receptors
#10
REVIEW
Steffen Backert, Nicole Tegtmeyer
Helicobacter pylori is a highly successful human bacterium, which is exceptionally equipped to persistently inhabit the human stomach. Colonization by this pathogen is associated with gastric disorders ranging from chronic gastritis and peptic ulcers to cancer. Highly virulent H. pylori strains express the well-established adhesins BabA/B, SabA, AlpA/B, OipA, and HopQ, and a type IV secretion system (T4SS) encoded by the cag pathogenicity island (PAI). The adhesins ascertain intimate bacterial contact to gastric epithelial cells, while the T4SS represents an extracellular pilus-like structure for the translocation of the effector protein CagA...
March 24, 2017: Toxins
https://www.readbyqxmd.com/read/28338617/egfr-family-members-regulation-of-autophagy-is-at-a-crossroads-of-cell-survival-and-death-in-cancer
#11
REVIEW
Elizabeth Henson, Yongqiang Chen, Spencer Gibson
The epidermal growth factor receptor (EGFR) signaling pathways are altered in many cancers contributing to increased cell survival. These alterations are caused mainly through increased expression or mutation of EGFR family members EGFR, ErbB2, ErbB3, and ErbB4. These receptors have been successfully targeted for cancer therapy. Specifically, a monoclonal antibody against ErbB2, trastuzumab, and a tyrosine kinase inhibitor against EGFR, gefitinib, have improved the survival of breast and lung cancer patients...
March 24, 2017: Cancers
https://www.readbyqxmd.com/read/28338568/pediatric-patient-with-renal-cell-carcinoma-treated-by-successive-antiangiogenics-drugs-a-case-report-and-review-of-the-literature
#12
Irene Jiménez, Hervé J Brisse, Paul Fréneaux, Sabine Sarnacki, Jean Michon, Daniel Orbach, Gaelle Pierron, Nathalie Clément, François Doz, Bernard Escudier, Gudrun Schleiermacher
Antiangiogenic drugs are currently standard of care in adults with renal cell carcinoma (RCC), including translocation RCC. Although antitumor activity and toxicity profile are well known in adults, few data have been reported in children. Here we present the case of a patient diagnosed at 2 years old with a metastatic translocation RCC, consecutively treated with 5 tyrosine kinase inhibitors during 6 years. The antitumor activity and toxic effects are described, and a brief review of the literature is presented...
March 23, 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/28338397/clove-and-its-active-compound-attenuate-free-fatty-acid-mediated-insulin-resistance-in-skeletal-muscle-cells-and-in-mice
#13
Safina Ghaffar, Shabbir Khan Afridi, Meha Fatima Aftab, Munazza Murtaza, Rahman M Hafizur, Sara Sara, Sabira Begum, Rizwana Sanaullah Waraich
Several reports indicate anti-hyperglycemic effects of Syzygium aromaticum. In the present study, we report for the first time that clove extract (SAM) and its compound nigricin (NGC) decreases free fatty acid-mediated insulin resistance in mouse myoblasts. In addition, NGC was able to diminish insulin resistance in a diabetic mouse model. We observed that SAM and its compound NGC exhibited significant antioxidant activity in murine skeletal muscle cells. They also modulated stress signaling by reducing p38 MAP kinase phosphorylation...
March 24, 2017: Journal of Medicinal Food
https://www.readbyqxmd.com/read/28338017/a-role-of-the-sam-domain-in-epha2-receptor-activation
#14
Xiaojun Shi, Vera Hapiak, Ji Zheng, Jeannine Muller-Greven, Deanna Bowman, Ryan Lingerak, Matthias Buck, Bing-Cheng Wang, Adam W Smith
Among the 20 subfamilies of protein receptor tyrosine kinases (RTKs), Eph receptors are unique in possessing a sterile alpha motif (SAM domain) at their C-terminal ends. However, the functions of SAM domains in Eph receptors remain elusive. Here we report on a combined cell biology and quantitative fluorescence study to investigate the role of the SAM domain in EphA2 function. We observed elevated tyrosine autophosphorylation levels upon deletion of the EphA2 SAM domain (EphA2ΔS) in DU145 and PC3 prostate cancer cells and a skin tumor cell line derived from EphA1/A2 knockout mice...
March 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28337870/jak2-tyrosine-kinase-inhibitor-ag490-suppresses-cell-growth-and-invasion-of-gallbladder-cancer-cells-via-inhibition-of-jak2-stat3-signaling
#15
L X Fu, Q W Lian, J D Pan, Z L Xu, T M Zhou, B Ye
The Janus kinase-signal transducers and activators of transcription signaling pathway (JAK/STAT pathway) have displayed a critical role in tumor development and progression in multiple malignancies. Previous studies showed that inhibition of JAK/STAT signaling blocked cell growth and metastasis in cancer cells, however, the antitumor effects of JAK inhibitor AG490 on gallbladder cancer (GBC) have not been reported. Our present study aimed to investigate the effects and associated mechanisms of JAK inhibitor AG490 on cell growth, invasive potential and apoptosis in GBC cells (GBC-SD and SGC-996) indicated by MTT, cell colony formation, Transwell and flow cytometry...
January 2017: Journal of Biological Regulators and Homeostatic Agents
https://www.readbyqxmd.com/read/28337773/histone-h2b-monoubiquitination-regulates-salt-stress-induced-microtubule-depolymerization-in-arabidopsis
#16
Sa Zhou, Qiuhong Chen, Yuhui Sun, Yingzhang Li
Histone H2B monoubiquitination (H2Bub1) is recognized as a regulatory mechanism that controls a range of cellular processes. We previously showed that H2Bub1 was involved in responses to biotic stress in Arabidopsis. However, the molecular regulatory mechanisms of H2Bub1 in controlling responses to abiotic stress remain limited. Here, we report that HISTONE MONOUBIQUITINATION1 (HUB1) and HUB2 played important regulatory roles in response to salt stress. Phenotypic analysis revealed that H2Bub1 mutants confer decreased tolerance to salt stress...
March 24, 2017: Plant, Cell & Environment
https://www.readbyqxmd.com/read/28337595/first-trimester-ttr-rbp4-roh-complex-and-angiogenic-factors-in-the-prediction-of-small-for-gestational-age-infant-s-outcome
#17
Arrigo Fruscalzo, Julia Frommer, Ambrogio P Londero, Andrea Henze, Florian J Schweigert, Jerzy-Roch Nofer, Johannes Steinhard, Walter Klockenbusch, Ralf Schmitz, Jens Raila
PURPOSE: To study the role of the TTR-RBP4-ROH complex components (transthyretin, serum retinol binding protein, retinol) and of angiogenic factors PlGF (placental growth factor) and sFlt-1 (soluble fms-like tyrosine kinase-1) in pregnancies complicated by small for gestational age infants (SGA). METHODS: Case control study conducted on maternal serum collected between 11 + 0 to 13 + 6 weeks of gestation. TTR, RBP4, ROH, PlGF and sFlt-1 were measured in SGA patients (birth weight <10%) who delivered at term (n = 37) and before 37 weeks of gestation (n = 17) and in a matched control group with uneventful pregnancies (n = 37)...
March 23, 2017: Archives of Gynecology and Obstetrics
https://www.readbyqxmd.com/read/28337541/tyrosine-kinase-inhibitor-therapy-induced-changes-in-humoral-immunity-in-patients-with-chronic-myeloid-leukemia
#18
Hanna L M Rajala, Mohamed El Missiry, Anniina Ruusila, Perttu Koskenvesa, Tim H Brümmendorf, Bjorn T Gjertsen, Jeroen Janssen, Kourosh Lotfi, Berit Markevärn, Ulla Olsson-Strömberg, Leif Stenke, Jesper Stentoft, Johan Richter, Henrik Hjorth-Hansen, Anna Kreutzman, Satu Mustjoki
PURPOSE: Tyrosine kinase inhibitors (TKIs) have well-characterized immunomodulatory effects on T and NK cells, but the effects on the humoral immunity are less well known. In this project, we studied TKI-induced changes in B cell-mediated immunity. METHODS: We collected peripheral blood (PB) and bone marrow (BM) samples from chronic myeloid leukemia (CML) patients before and during first-line imatinib (n = 20), dasatinib (n = 16), nilotinib (n = 8), and bosutinib (n = 12) treatment...
March 23, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28337370/role-of-epidermal-growth-factor-receptor-in-lung-cancer-and-targeted-therapies
#19
REVIEW
Tie-Cheng Liu, Xin Jin, Yan Wang, Ke Wang
Lung cancer is the foremost cause of cancer-related deaths world-wide. Both, the major forms of lung cancer, Non-small cell lung cancer (NSCLC) and Small cell lung cancers (SCLC), have responded effectively to chemo-, radiation and adjuvant-therapies. Tumor removal through surgery also appeared as a good therapeutic strategy. However, these therapies demonstrated unfavourable side-effects, and hence novel drugs targeting lung cancer emerged essential. Activation of epidermal growth factor receptor (EGFR)-tyrosine kinases is a key reason for lung cancer progression...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/28337120/antidyskinetic-effects-of-mek-inhibitor-are-associated-with-multiple-neurochemical-alterations-in-the-striatum-of-hemiparkinsonian-rats
#20
Guiqin Chen, Shuke Nie, Chao Han, Kai Ma, Yan Xu, Zhentao Zhang, Stella M Papa, Xuebing Cao
L-DOPA-induced dyskinesia (LID) represents one of the major problems of the long-term therapy of patients with Parkinson's disease (PD). Although, the pathophysiologic mechanisms underlying LID are not completely understood, activation of the extracellular signal regulated kinase (ERK) is recognized to play a key role. ERK is phosphorylated by mitogen-activated protein kinase kinase (MEK), and thus MEK inhibitor can prevent ERK activation. Here the effect of the MEK inhibitor PD98059 on LID and the associated molecular changes were examined...
2017: Frontiers in Neuroscience
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