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https://www.readbyqxmd.com/read/28343336/sunitinib-induced-hypothyroidism-predicts-progression-free-survival-in-metastatic-renal-cell-carcinoma-patients
#1
Anna Buda-Nowak, Jakub Kucharz, Paulina Dumnicka, Marek Kuzniewski, Roman Maria Herman, Aneta L Zygulska, Beata Kusnierz-Cabala
Sunitinib is a tyrosine kinase inhibitor (TKI) used in treatment of metastatic renal cell carcinoma (mRCC), gastrointestinal stromal tumors and pancreatic neuroendocrine tumors. One of the most common side effects related to sunitinib is hypothyroidism. Recent trials suggest correlation between the incidence of hypothyroidism and treatment outcome in patients treated with TKI. This study evaluates whether development of hypothyroidism is a predictive marker of progression-free survival (PFS) in patients with mRCC treated with sunitinib...
April 2017: Medical Oncology
https://www.readbyqxmd.com/read/28342996/induction-of-neuroendocrine-differentiation-in-prostate-cancer-cells-by-dovitinib-tki-258-and-its-therapeutic-implications
#2
Shalini S Yadav, Jinyi Li, Jennifer A Stockert, Bryan Herzog, James O'Connor, Luis Garzon-Manco, Ramon Parsons, Ashutosh K Tewari, Kamlesh K Yadav
Prostate cancer (PCa) remains the second-leading cause of cancer-related deaths in American men with an estimated mortality of more than 26,000 in 2016 alone. Aggressive and metastatic tumors are treated with androgen deprivation therapies (ADT); however, the tumors acquire resistance and develop into lethal castration resistant prostate cancer (CRPC). With the advent of better therapeutics, the incidences of a more aggressive neuroendocrine prostate cancer (NEPC) variant continue to emerge. Although de novo occurrences of NEPC are rare, more than 25% of the therapy-resistant patients on highly potent new-generation anti-androgen therapies end up with NEPC...
March 23, 2017: Translational Oncology
https://www.readbyqxmd.com/read/28340283/comparative-analysis-of-pulmonary-hypertension-in-patients-treated-with-imatinib-nilotinib-and-dasatinib
#3
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
#4
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/28339691/z-guggulsterone-produces-antidepressant-like-effects-in-mice-through-activation-of-the-bdnf-signaling-pathway
#5
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
#6
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/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/28338617/egfr-family-members-regulation-of-autophagy-is-at-a-crossroads-of-cell-survival-and-death-in-cancer
#9
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
#10
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/28337870/jak2-tyrosine-kinase-inhibitor-ag490-suppresses-cell-growth-and-invasion-of-gallbladder-cancer-cells-via-inhibition-of-jak2-stat3-signaling
#11
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/28337541/tyrosine-kinase-inhibitor-therapy-induced-changes-in-humoral-immunity-in-patients-with-chronic-myeloid-leukemia
#12
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
#13
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
#14
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
https://www.readbyqxmd.com/read/28336955/progress-of-antibody-based-inhibitors-of-the-hgf-cmet-axis-in-cancer-therapy
#15
REVIEW
Ki-Hyun Kim, Hyori Kim
Dysregulated receptor tyrosine kinase signaling in human cancer cells leads to tumor progression, invasion and metastasis. The receptor tyrosine kinase cMET is frequently overexpressed in cancer tissue, and activation of cMET signaling is related to drug resistance and the processes of carcinogenesis, invasion and metastasis. For that reason, cMET and its ligand, hepatocyte growth factor (HGF), are considered prime targets for the development of anticancer drugs. At least eight anti-cMET and four anti-HGF antibodies have been tested or are being tested in clinical trials...
March 24, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28336808/potent-dual-bet-bromodomain-kinase-inhibitors-as-value-added-multi-targeted-chemical-probes-and-cancer-therapeutics
#16
Stuart W Ember, Que T Lambert, Norbert Berndt, Steven Gunawan, Muhammad Ayaz, Marilena Tauro, Jin-Yi Zhu, Paula J Cranfill, Patricia Greninger, Conor C Lynch, Cyril H Benes, Harshani R Lawrence, Gary W Reuther, Nicholas J Lawrence, Ernst Schonbrunn
Synergistic action of kinase and BET bromodomain inhibitors in cell killing has been reported for a variety of cancers. Using the chemical scaffold of the JAK2 inhibitor TG101348 we developed and characterized single agents which potently and simultaneously inhibit BRD4 and a specific set of oncogenic tyrosine kinases including JAK2, FLT3, RET, and ROS1. Lead compounds showed on-target inhibition in several blood cancer cell lines and were highly efficacious at inhibiting the growth of hematopoietic progenitor cells from myeloproliferative neoplasm (MPN) patients...
March 23, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28336715/monitoring-cell-surface-n-glycoproteome-dynamics-by-quantitative-proteomics-reveals-mechanistic-insights-into-macrophage-differentiation
#17
Mathias Kalxdorf, Stephan Gade, H Christian Eberl, Marcus Bantscheff
The plasma membrane proteome plays a crucial role in inter- and intracellular signaling, cell survival and cell identity. As such it is a prominent target for pharmacological intervention. The relatively low abundance of this subproteome in conjunction with challenging extractability and solubility still hampers their comprehensive analysis. Here, we combined a chemical glycoprotein tagging strategy with mass spectrometry to enable comprehensive analysis of the cell surface glycoprotome. To benchmark this workflow and provide guidance for cell line selection for functional experiments, we generated an inventory of the N-linked cell surface glycoproteome of 15 standard laboratory human cell lines and three primary lymphocytic cell types...
March 23, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28336564/identification-of-a-novel-syk-c-myc-malat1-signaling-pathway-and-its-potential-therapeutic-value-in-ewing-sarcoma
#18
Haibo Sun, De-Chen Lin, Qi Cao, Brendan Pang, David D Gae, Victor Km Lee, Huey Jin Lim, Ngan Doan, Jonathan W Said, Sigal Gery, Marilynn Chow, Anand Mayakonda, Charles Forscher, Jeffrey W Tyner, H Phillip Koeffler
PURPOSE: Ewing Sarcoma (EWS) is a devastating soft tissue sarcoma affecting predominantly young individuals. Tyrosine kinases (TKs) and associated pathways are continuously activated in many malignancies including EWS; these enzymes provide candidate therapeutic targets. EXPERIMENTAL DESIGN: Two high-throughput screens (a siRNA library and a small-molecule inhibitor library) were performed in EWS cells to establish candidate targets. Spleen tyrosine kinase (SYK) phosphorylation was assessed in EWS patients and cell lines...
March 23, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28336561/mice-lacking-the-inhibitory-collagen-receptor-lair-1-exhibit-a-mild-thrombocytosis-and-hyperactive-platelets
#19
Christopher W Smith, Steven G Thomas, Zaher Raslan, Pushpa Patel, Maxwell Byrne, Marie Lordkipanidzé, Danai Bem, Linde Meyaard, Yotis A Senis, Steve P Watson, Alexandra Mazharian
OBJECTIVE: Leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1) is a collagen receptor that belongs to the inhibitory immunoreceptor tyrosine-based inhibition motif-containing receptor family. It is an inhibitor of signaling via the immunoreceptor tyrosine-based activation motif-containing collagen receptor complex, glycoprotein VI-FcRγ-chain. It is expressed on hematopoietic cells, including immature megakaryocytes, but is not detectable on platelets. Although the inhibitory function of LAIR-1 has been described in leukocytes, its physiological role in megakaryocytes and in particular in platelet formation has not been explored...
March 23, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28336299/inhibitory-effect-of-crizotinib-on-creatinine-uptake-by-renal-secretory-transporter-oct2
#20
Hiroshi Arakawa, Saki Omote, Ikumi Tamai
Crizotinib, a tyrosine kinase inhibitor, exhibits some cases of an increase in serum creatinine levels. Creatinine is secreted by not only glomerular filtration, but also active secretion by organic cation transporters such as organic cation transporter 2 (OCT2). In the present study, we evaluated in vitro inhibitory effect of crizotinib on OCT2 by directly measuring creatinine uptake by OCT2. Co-incubation of crizotinib reduced uptake of [(14)C]creatinine by cultured HEK293 cells expressing OCT2 (HEK293/OCT2) in a concentration-dependent manner with IC50 values of 1...
March 20, 2017: Journal of Pharmaceutical Sciences
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