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https://www.readbyqxmd.com/read/29455653/novel-targeted-therapies-and-immunotherapy-for-advanced-thyroid-cancers
#1
REVIEW
George E Naoum, Michael Morkos, Brian Kim, Waleed Arafat
Thyroid cancer is a frequently encountered endocrine malignancy. Despite the favorable prognosis of this disease, 15-20% of differentiated thyroid cancer (DTC) cases and most anaplastic types, remain resistant to standard treatment options, including radioactive iodine (RAI). In addition, around 30% of medullary thyroid cancer (MTC) cases show resistance after surgery. The evolving understanding of disease-specific molecular therapeutic targets has led to the approval of two targeted therapies (Sorafenib and Lenvatinib) for RAI refractory DTC and another two drugs (Vandetanib and Cabozantinib) for MTC...
February 19, 2018: Molecular Cancer
https://www.readbyqxmd.com/read/29455554/synthesis-antitumour-and-antioxidant-activities-of-novel-%C3%AE-%C3%AE-unsaturated-ketones-and-related-heterocyclic-analogues-egfr-inhibition-and-molecular-modelling-study
#2
Walaa M El-Husseiny, Magda A-A El-Sayed, Naglaa I Abdel-Aziz, Adel S El-Azab, Esam R Ahmed, Alaa A-M Abdel-Aziz
New α,β-unsaturated ketones 4a,b; 5a-c; and 6a,b; as well as 4-H pyran 7; pyrazoline 8a,b; isoxazoline 9; pyridine 10-11; and quinoline-4-carboxylic acid 12a,b derivatives were synthesized and evaluated for in vitro antitumour activity against HepG2, MCF-7, HeLa, and PC-3 cancer cell lines. Antioxidant activity was investigated by the ability of these compounds to scavenge the 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) radical cation (ABTS•+ ). Compounds 6a, 6b, 7, and 8b exhibited potent antitumour activities against all tested cell lines with [IC50 ] ≅5...
December 2018: Journal of Enzyme Inhibition and Medicinal Chemistry
https://www.readbyqxmd.com/read/29455421/impact-of-baseline-characteristics-on-outcomes-of-advanced-hcc-patients-treated-with-sorafenib-a-secondary-analysis-of-a-phase-iii-study
#3
Omar Abdel-Rahman
BACKGROUND: The current study aims to investigate the impact of baseline characteristics on the outcomes of sorafenib-treated advanced Hepatocellular carcinoma (HCC) patients in the setting of a clinical trial. METHODS: This is a secondary analysis of the comparator arm (sorafenib arm) of the NCT00699374 study which is a phase III multicenter study conducted between 2008 and 2010. The univariate probability of overall and progression-free survival was assessed among different patient subsets through Kaplan-Meier analysis and log-rank testing...
February 17, 2018: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/29454306/record-4-multicenter-phase-2-trial-of-second-line-everolimus-in-patients-with-metastatic-renal-cell-carcinoma-asian-versus-non-asian-population-subanalysis
#4
Lin Yang, Anna Alyasova, Dingwei Ye, Antonia Ridolfi, Luca Dezzani, Robert J Motzer
BACKGROUND: RECORD-4 assessed everolimus in patients with metastatic renal cell carcinoma (mRCC) who progressed after 1 prior anti-vascular endothelial growth factor (VEGF) or cytokine and reinforced the clinical benefit of second-line everolimus. Because of the high percentage of patients from China enrolled in RECORD-4 (41%) and some reported differences in responses to certain targeted agents between Chinese and Western patients, this subanalysis evaluated outcomes in Asian versus non-Asian patients...
February 17, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29454091/anlotinib-inhibits-angiogenesis-via-suppressing-the-activation-of-vegfr2-pdgfr%C3%AE-and-fgfr1
#5
Binyan Lin, Xiuming Song, Dawei Yang, Dongsheng Bai, Yuyuan Yao, Na Lu
Tumor cells recruit vascular endothelial cells and circulating endothelial progenitor cells to form new vessels to support their own growth and metastasis. VEGF, PDGF-BB and FGF-2 are three major pro-angiogenic factors and applied to promote angiogenesis. In this research, we demonstrated that anlotinib, a potent multi-tyrosine kinases inhibitor (TKI), showed a significant inhibitory effect on VEGF/PDGF-BB/FGF-2-induced angiogenesis in vitro and in vivo. Wound healing assay, chamber directional migration assay and tube formation assay indicated that anlotinib inhibited VEGF/PDGF-BB/FGF-2-induced cell migration and formation of capillary-like tubes in endothelial cells...
February 14, 2018: Gene
https://www.readbyqxmd.com/read/29453869/erythema-nodosum-like-eruption-in-the-setting-of-sorafenib-therapy
#6
Emily L Coleman, Shawn E Cowper, Stacey M Stein, Jonathan S Leventhal
No abstract text is available yet for this article.
February 16, 2018: JAMA Dermatology
https://www.readbyqxmd.com/read/29453759/systemic-treatment-of-patients-with-advanced-unresectable-hepatocellular-carcinoma-emergence-of-therapies
#7
REVIEW
Weijing Sun, Roniel Cabrera
To date, sorafenib, a multiple tyrosine kinase inhibitor, is the only systemic agent approved by the FDA in the first-line treatment of patients with unresectable hepatocellular carcinoma (HCC). Several other tyrosine kinase-inhibiting agents have been investigated in the first-line setting, either alone (sunitinib, brivanib, linifanib, and lenvatinib) or in combination with sorafenib (erlotinib and doxorubicin) in phase 3 trials. However, none of these studies demonstrated an improvement in survival over sorafenib...
February 17, 2018: Journal of Gastrointestinal Cancer
https://www.readbyqxmd.com/read/29449645/egfr-pi3k-pdk1-pathway-regulates-yap-signaling-in-hepatocellular-carcinoma-the-mechanism-and-its-implications-in-targeted-therapy
#8
Hongwei Xia, Xinyu Dai, Huangfei Yu, Sheng Zhou, Zhenghai Fan, Guoqing Wei, Qiulin Tang, Qiyong Gong, Feng Bi
The epidermal growth factor receptor (EGFR) pathway and Hippo signaling play an important role in the carcinogenesis of hepatocellular carcinoma (HCC). However, the crosstalk between these two pathways and its implications in targeted therapy remains unclear. We found that the activated EGFR signaling could bypass RhoA to promote the expression of YAP(Yes-associated protein), the core effector of the Hippo signaling, and its downstream target Cyr61. Further studies indicated that EGFR signaling mainly acted through the PI3K-PDK1 (Phosphoinositide 3-kinase-Phosphoinositide-dependent kinase-1) pathway to activate YAP, but not the AKT and MAPK pathways...
February 15, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29449091/adjuvant-therapies-in-nonmetastatic-renal-cell-carcinoma-a-review-of-the-literature
#9
REVIEW
Marco Bandini, Ariane Smith, Michele Marchioni, Raisa S Pompe, Tristan F Martel, Luca Cindolo, Francesco Montorsi, Shahrokh F Shariat, Alberto Briganti, Anil Kapoor, Umberto Capitanio, Pierre I Karakiewicz
To conduct a review of literature on adjuvant therapy in nonmetastatic renal-cell carcinoma (nmRCC) treated with nephrectomy and to describe the efficacy of adjuvant agents on cancer control outcomes. A review of the literature was performed in January 2018 to identify all studies evaluating adjuvant therapy in patients with nmRCC treated with nephrectomy using PubMed, Embase, Medline, and Cochrane Library databases. The following keywords were used: adjuvant therapy, renal-cell carcinoma, nonmetastatic, targeted molecular therapy, kidney cancer...
February 2, 2018: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/29446053/systems-pharmacological-analysis-of-mitochondrial-cardiotoxicity-induced-by-selected-tyrosine-kinase-inhibitors
#10
Tanaya Vaidya, Jeff Kamta, Maher Chaar, Anusha Ande, Sihem Ait-Oudhia
Tyrosine kinase inhibitors (TKIs) are targeted therapies rapidly becoming favored over conventional cytotoxic chemotherapeutics. Our study investigates two FDA approved TKIs, DASATINIB; indicated for IMATINIB-refractory chronic myeloid leukemia, and SORAFENIB; indicated for hepatocellular carcinoma and advanced renal cell carcinoma. Limited but crucial evidence suggests that these agents can have cardiotoxic side effects ranging from hypertension to heart failure. A greater understanding of the underlying mechanisms of this cardiotoxicity are needed as concerns grow and the capacity to anticipate them is lacking...
February 14, 2018: Journal of Pharmacokinetics and Pharmacodynamics
https://www.readbyqxmd.com/read/29445127/cripto-1-contributes-to-stemness-in-hepatocellular-carcinoma-by-stabilizing-dishevelled-3-and-activating-wnt-%C3%AE-catenin-pathway
#11
Regina Cheuk-Lam Lo, Carmen Oi-Ning Leung, Kristy Kwan-Shuen Chan, Daniel Wai-Hung Ho, Chun-Ming Wong, Terence Kin-Wah Lee, Irene Oi-Lin Ng
Identification and characterization of functional molecular targets conferring stemness properties in hepatocellular carcinoma (HCC) offers crucial insights to overcome the major hurdles of tumor recurrence, metastasis and chemoresistance in clinical management. In the current study, we investigated the significance of Cripto-1 in contributing to HCC stemness. Cripto-1 was upregulated in the sorafenib-resistant clones derived from HCC cell lines and patient-derived xenograft that we previously developed, suggesting an association between Cripto-1 and stemness...
February 14, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29445087/rage-induces-hepatocellular-carcinoma-proliferation-and-sorafenib-resistance-by-modulating-autophagy
#12
Jun Li, Peng-Wen Wu, Yuan Zhou, Bo Dai, Peng-Fei Zhang, Yu-Hen Zhang, Yang Liu, Xiao-Lei Shi
The receptor for advanced glycation end products (Rage) is involved in the development of various tumors and acts as an oncogenic protein. Rage is overexpressed in tumors including hepatocellular carcinoma (HCC). However, the molecular mechanism of Rage in HCC progression and sorafenib resistance remains unclear. In this study, enhanced Rage expression is highly associated proliferation and contributes to sorafenib resistance. Rage deficiency contributed to autophagy induction through activating AMPK/mTOR signaling pathway, which is important for sorafenib response...
February 14, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29437468/dual-flt3-topk-inhibitor-with-activity-against-flt3-itd-secondary-mutations-potently-inhibits-acute-myeloid-leukemia-cell-lines
#13
Neetu Dayal, Clement Opoku-Temeng, Delmis E Hernandez, Moloud Aflaki Sooreshjani, Brandon A Carter-Cooper, Rena G Lapidus, Herman O Sintim
AIM: Approximately 30% of acute myeloid leukemia (AML) patients carry FLT3 tyrosine kinase domain (TKD) mutations or internal tandem duplication (FLT3-ITD). Currently there is a paucity of compounds that are active against drug-resistant FLT3-ITD, which contains secondary mutations in the TKD, mainly at residues D835/F691. RESULTS: HSD1169, a novel compound, is active against FLT3-ITD (D835 or F691). HSD1169 is also active against T-LAK cell-originated protein kinase (TOPK), a collaborating kinase that is highly expressed in AML cell lines...
February 13, 2018: Future Medicinal Chemistry
https://www.readbyqxmd.com/read/29436591/downregulation-of-secreted-clusterin-potentiates-the-lethality-of-sorafenib-in-hepatocellular-carcinoma-in-association-with-the-inhibition-of-erk1-2-signals
#14
Jingtao Zhong, Xiaoming Yu, Xiaofeng Dong, Hong Lu, Wuyuan Zhou, Lei Li, Zhongchao Li, Pengfei Sun, Xuetao Shi
Secretory clusterin (sCLU) is overexpressed in cancer and is associated with resistance to chemotherapy in several types of cancer, including hepatocellular carcinoma (HCC). Sorafenib (SOR), a multikinase inhibitor of Raf/mitogen‑activated protein kinase kinase/extracellular signal‑regulated kinase (ERK) signaling and the receptor tyrosine kinase, is recognized as the standard therapeutic strategy for patients with advanced HCC. However, the role of sCLU in the resistance of HCC to SOR remains to be fully elucidated...
February 6, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29435166/acquired-resistance-to-tyrosine-kinase-inhibitors-may-be-linked-with-the-decreased-sensitivity-to-x-ray-irradiation
#15
Maxim Sorokin, Roman Kholodenko, Anna Grekhova, Maria Suntsova, Margarita Pustovalova, Natalia Vorobyeva, Irina Kholodenko, Galina Malakhova, Andrew Garazha, Artem Nedoluzhko, Raif Vasilov, Elena Poddubskaya, Olga Kovalchuk, Leila Adamyan, Vladimir Prassolov, Daria Allina, Denis Kuzmin, Kirill Ignatev, Andreyan Osipov, Anton Buzdin
Acquired resistance to chemotherapy and radiation therapy is one of the major obstacles decreasing efficiency of treatment of the oncologic diseases. In this study, on the two cell lines (ovarian carcinoma SKOV-3 and neuroblastoma NGP-127), we modeled acquired resistance to five target anticancer drugs. The cells were grown on gradually increasing concentrations of the clinically relevant tyrosine kinase inhibitors (TKIs) Sorafenib, Pazopanib and Sunitinib, and rapalogs Everolimus and Temsirolimus, for 20 weeks...
January 12, 2018: Oncotarget
https://www.readbyqxmd.com/read/29433850/lenvatinib-versus-sorafenib-in-first-line-treatment-of-patients-with-unresectable-hepatocellular-carcinoma-a-randomised-phase-3-non-inferiority-trial
#16
Masatoshi Kudo, Richard S Finn, Shukui Qin, Kwang-Hyub Han, Kenji Ikeda, Fabio Piscaglia, Ari Baron, Joong-Won Park, Guohong Han, Jacek Jassem, Jean Frederic Blanc, Arndt Vogel, Dmitry Komov, T R Jeffry Evans, Carlos Lopez, Corina Dutcus, Matthew Guo, Kenichi Saito, Silvija Kraljevic, Toshiyuki Tamai, Min Ren, Ann-Lii Cheng
BACKGROUND: In a phase 2 trial, lenvatinib, an inhibitor of VEGF receptors 1-3, FGF receptors 1-4, PDGF receptor α, RET, and KIT, showed activity in hepatocellular carcinoma. We aimed to compare overall survival in patients treated with lenvatinib versus sorafenib as a first-line treatment for unresectable hepatocellular carcinoma. METHODS: This was an open-label, phase 3, multicentre, non-inferiority trial that recruited patients with unresectable hepatocellular carcinoma, who had not received treatment for advanced disease, at 154 sites in 20 countries throughout the Asia-Pacific, European, and North American regions...
February 9, 2018: Lancet
https://www.readbyqxmd.com/read/29431743/sorafenib-promotes-graft-versus-leukemia-activity-in-mice-and-humans-through-il-15-production-in-flt3-itd-mutant-leukemia-cells
#17
Nimitha R Mathew, Francis Baumgartner, Lukas Braun, David O'Sullivan, Simone Thomas, Miguel Waterhouse, Tony A Müller, Kathrin Hanke, Sanaz Taromi, Petya Apostolova, Anna L Illert, Wolfgang Melchinger, Sandra Duquesne, Annette Schmitt-Graeff, Lena Osswald, Kai-Li Yan, Arnim Weber, Sonia Tugues, Sabine Spath, Dietmar Pfeifer, Marie Follo, Rainer Claus, Michael Lübbert, Christoph Rummelt, Hartmut Bertz, Ralph Wäsch, Johanna Haag, Andrea Schmidts, Michael Schultheiss, Dominik Bettinger, Robert Thimme, Evelyn Ullrich, Yakup Tanriver, Giang Lam Vuong, Renate Arnold, Philipp Hemmati, Dominik Wolf, Markus Ditschkowski, Cordula Jilg, Konrad Wilhelm, Christian Leiber, Sabine Gerull, Jörg Halter, Claudia Lengerke, Thomas Pabst, Thomas Schroeder, Guido Kobbe, Wolf Rösler, Soroush Doostkam, Stephan Meckel, Kathleen Stabla, Stephan K Metzelder, Sebastian Halbach, Tilman Brummer, Zehan Hu, Joern Dengjel, Björn Hackanson, Christoph Schmid, Udo Holtick, Christof Scheid, Alexandros Spyridonidis, Friedrich Stölzel, Rainer Ordemann, Lutz P Müller, Flore Sicre-de-Fontbrune, Gabriele Ihorst, Jürgen Kuball, Jan E Ehlert, Daniel Feger, Eva-Maria Wagner, Jean-Yves Cahn, Jacqueline Schnell, Florian Kuchenbauer, Donald Bunjes, Ronjon Chakraverty, Simon Richardson, Saar Gill, Nicolaus Kröger, Francis Ayuk, Luca Vago, Fabio Ciceri, Antonia M Müller, Takeshi Kondo, Takanori Teshima, Susan Klaeger, Bernhard Kuster, Dennis Dong Hwan Kim, Daniel Weisdorf, Walter van der Velden, Daniela Dörfel, Wolfgang Bethge, Inken Hilgendorf, Andreas Hochhaus, Geoffroy Andrieux, Melanie Börries, Hauke Busch, John Magenau, Pavan Reddy, Myriam Labopin, Joseph H Antin, Andrea S Henden, Geoffrey R Hill, Glen A Kennedy, Merav Bar, Anita Sarma, Donal McLornan, Ghulam Mufti, Betul Oran, Katayoun Rezvani, Omid Sha, Robert S Negrin, Arnon Nagler, Marco Prinz, Andreas Burchert, Andreas Neubauer, Dietrich Beelen, Andreas Mackensen, Nikolas von Bubnoff, Wolfgang Herr, Burkhard Becher, Gerard Socié, Michael A Caligiuri, Eliana Ruggiero, Chiara Bonini, Georg Häcker, Justus Duyster, Jürgen Finke, Erika Pearce, Bruce R Blazar, Robert Zeiser
Individuals with acute myeloid leukemia (AML) harboring an internal tandem duplication (ITD) in the gene encoding Fms-related tyrosine kinase 3 (FLT3) who relapse after allogeneic hematopoietic cell transplantation (allo-HCT) have a 1-year survival rate below 20%. We observed that sorafenib, a multitargeted tyrosine kinase inhibitor, increased IL-15 production by FLT3-ITD+ leukemia cells. This synergized with the allogeneic CD8+ T cell response, leading to long-term survival in six mouse models of FLT3-ITD+ AML...
February 12, 2018: Nature Medicine
https://www.readbyqxmd.com/read/29428943/comparison-of-outcome-of-hepatic-arterial-infusion-chemotherapy-combined-with-radiotherapy-and-sorafenib-for-advanced-hepatocellular-carcinoma-patients-with-major-portal-vein-tumor-thrombosis
#18
Kenichiro Kodama, Tomokazu Kawaoka, Hiroshi Aikata, Shinsuke Uchikawa, Yuno Nishida, Yuki Inagaki, Masahiro Hatooka, Kei Morio, Takashi Nakahara, Eisuke Murakami, Masataka Tsuge, Akira Hiramatsu, Michio Imamura, Yoshiiku Kawakami, Keiichi Masaki, Yoji Honda, Nami Mori, Shintaro Takaki, Keiji Tsuji, Hirotaka Kohno, Hiroshi Kohno, Takashi Moriya, Michihiro Nonaka, Hideyuki Hyogo, Yasuyuki Aisaka, Tomoki Kimura, Yasushi Nagata, Kazuaki Chayama
OBJECTIVE: To compare the outcome of hepatic arterial infusion chemotherapy combined with radiotherapy (HAIC + RT) versus sorafenib monotherapy in patients with advanced hepatocellular carcinoma (HCC) and major portal vein tumor thrombosis (PVTT). METHODS: This retrospective study included 108 HCC patients with PVTT of the main trunk or first branch and Child-Pugh ≤7. Sixty-eight received HAIC + RT and 40 received sorafenib. Patients were then assigned to the HAIC + RT group (n = 36) and the sorafenib group (n = 36) through case-control matching...
February 9, 2018: Oncology
https://www.readbyqxmd.com/read/29426804/escmid-study-group-for-infections-in-compromised-hosts-esgich-consensus-document-on-the-safety-of-targeted-and-biologic-therapies-an-infectious-diseases-perspective-cell-surface-receptors-and-associated-signaling-pathways
#19
REVIEW
J Aguilar-Company, M Fernández-Ruiz, R García-Campelo, A C Garrido-Castro, I Ruiz-Camps
BACKGROUND: The present review is part of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group for Infections in Compromised Hosts (ESGICH) consensus document on the safety of targeted and biologic therapies. AIMS: To review, from an infectious diseases perspective, the safety profile of therapies targeting cell surface receptors and associated signaling pathways among cancer patients and to suggest preventive recommendations...
February 6, 2018: Clinical Microbiology and Infection
https://www.readbyqxmd.com/read/29425861/effect-of-5-7-dimethoxyflavone-on-bcrp1-mediated-transport-of-sorafenib-in-vitro-and-in-vivo-in-mice
#20
SoHyun Bae, Ronilda D'Cunha, Jie Shao, Guohua An
Tyrosine kinase inhibitors (TKI) are a novel and target-specific class of anticancer drugs. One drawback of TKI therapy is cancer resistance to TKI. An important TKI resistance mechanism is enhanced efflux of TKI by efflux transporters, such as Breast Cancer Resistance Protein (BCRP), in cancer cells. 5,7-Dimethoxyflavone (5,7-DMF) is a natural flavonoid which was recently reported to be a potent BCRP inhibitor. In the current study, the effect of 5,7-DMF on the disposition of sorafenib, a TKI which is a good substrate of BCRP, was investigated both in vitro in efflux transporter expressing cells and in vivo in mice...
February 6, 2018: European Journal of Pharmaceutical Sciences
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