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https://www.readbyqxmd.com/read/28835855/chemotherapeutic-xct-inhibitors-sorafenib-and-erastin-unraveled-with-the-synaptic-optogenetic-function-analysis-tool
#1
Marc Dahlmanns, Eduard Yakubov, Daishi Chen, Tina Sehm, Manfred Rauh, Nicolai Savaskan, Jana Katharina Wrosch
In the search for new potential chemotherapeutics, the compounds' toxicity to healthy cells is an important factor. The brain with its functional units, the neurons, is especially endangered during the radio- and chemotherapeutic treatment of brain tumors. The effect of the potential compounds not only on neuronal survival but also neuronal function needs to be taken into account. Therefore, in this study we aimed to comprehend the biological effects of chemotherapeutic xCT inhibition on healthy neuronal cells with our synaptic optogenetic function analysis tool (SOFA)...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/28673964/sorafenib-targets-the-mitochondrial-electron-transport-chain-complexes-and-atp-synthase-to-activate-the-pink1-parkin-pathway-and-modulate-cellular-drug-response
#2
Conggang Zhang, Zeyu Liu, Eric Bunker, Adrian Ramirez, Schuyler Lee, Yinghua Peng, Aik-Choon Tan, S Gail Eckhardt, Douglas A Chapnick, Xuedong Liu
Sorafenib (Nexavar) is a broad-spectrum multikinase inhibitor that proves effective in treating advanced renal-cell carcinoma and liver cancer. Despite its well-characterized mechanism of action on several established cancer-related protein kinases, sorafenib causes variable responses among human tumors, although the cause for this variation is unknown. In an unbiased screening of an oncology drug library, we found that sorafenib activates recruitment of the ubiquitin E3 ligase Parkin to damaged mitochondria...
September 8, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28651299/survival-estimates-after-stopping-sorafenib-in-patients-with-hepatocellular-carcinoma-next-score-development-and-validation
#3
Hye Won Lee, Hyun Soo Kim, Seung Up Kim, Do Young Kim, Beom Kyung Kim, Jun Yong Park, Sang Hoon Ahn, Mi Young Jeon, Ja Yoon Heo, Soo Young Park, Yu Rim Lee, Sun Kyung Jang, Su Hyun Lee, Se Young Jang, Won Young Tak, Kwang-Hyub Han
Background/Aims: Limited information is available regarding patient survival after sorafenib discontinuation in patients with hepatocellular carcinoma (HCC). Thus, we developed and validated a novel survival prediction model. Methods: Clinical data from 409 patients with HCC who stopped taking sorafenib between September 2008 and February 2015 were reviewed. Results: In the training cohort, four factors were independent negative predictors of survival (p<0...
September 15, 2017: Gut and Liver
https://www.readbyqxmd.com/read/28486081/cost-effectiveness-of-lenvatinib-sorafenib-and-placebo-in-treatment-of-radioiodine-refractory-differentiated-thyroid-cancer
#4
Leslie Wilson, Wei Huang, Linda Chen, Jie Ting, Vicky Cao
BACKGROUND: Lenvatinib (Lenvima(®)) and sorafenib (Nexavar(®)) are the two most recently Food and Drug Administration-approved drugs for treating radioiodine-refractory differentiated thyroid cancer (RR-DTC). Both demonstrated superior progression-free survival over placebo in their respective Phase III clinical trials. This study compared the cost-effectiveness of the two treatments with placebo from a limited societal perspective. METHODS: A Markov model was developed to estimate the costs and health benefits for treatment of RR-DTC...
August 2017: Thyroid: Official Journal of the American Thyroid Association
https://www.readbyqxmd.com/read/28299600/sorafenib-a-review-in-hepatocellular-carcinoma
#5
REVIEW
Gillian M Keating
Sorafenib (Nexavar(®)) is currently the only systemic agent approved for use in hepatocellular carcinoma (HCC). Its approval was based on the results of the pivotal SHARP and Sorafenib Asia-Pacific (AP) trials in Child-Pugh (CP) class A patients with advanced HCC, which showed significantly longer median overall survival (OS) and time to radiological progression (TTP) with sorafenib 400 mg twice daily than with placebo, with no significant between-group difference in the median time to symptomatic progression (TTSP)...
April 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28039697/s-1-plus-sorafenib-for-the-treatment-of-advanced-hepatocellular-carcinoma
#6
REVIEW
Wukui Huang, Lina You, Dengyao Liu, Shufa Yang, Mo Liu, Hailin Wang, Pingju Wang, Pahaerding Baikere, Peng Gu, Abulajiang Abulikemu, Shaoha Yuan, Xiwen Fan
PURPOSE: To assess the efficacy and safety of S-1 plus sorafenib for the treatment of advanced hepatocellular carcinoma (HCC). METHODS: PubMed, the Cochrane Library, EMBASE, and ClinicalTrials.gov were searched using the terms "Hepatocellular Carcinoma" or "HCC" or "Hepatoma" or "Liver cancer" and "S-1" and "Sorafenib" or "Nexavar". Outcomes of main interest included overall survival (OS) and toxicities. RESULTS: We identified 2 studies of S"1 plus sorafenib from 77 references that included a total of 65 patients...
November 2016: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/27965580/osu-2s-sorafenib-synergistic-antitumor-combination-against-hepatocellular-carcinoma-the-role-of-pkc%C3%AE-p53
#7
Hany A Omar, Mai F Tolba, Jui-Hsiang Hung, Taleb H Al-Tel
Background: Sorafenib (Nexavar(®)) is an FDA-approved systemic therapy for advanced hepatocellular carcinoma (HCC). However, the low efficacy and adverse effects at high doses limit the clinical application of sorafenib and strongly recommend its combination with other agents aiming at ameliorating its drawbacks. OSU-2S, a PKCδ activator, was selected as a potential candidate anticancer agent to be combined with sorafenib to promote the anti-cancer activity through synergistic interaction. Methods: The antitumor effects of sorafenib, OSU-2S and their combination were assessed by MTT assay, caspase activation, Western blotting, migration/invasion assays in four different HCC cell lines...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27825923/the-antitumor-activity-of-a-lactosaminated-albumin-conjugate-of-doxorubicin-in-a-chemically-induced-hepatocellular-carcinoma-rat-model-compared-to-sorafenib
#8
COMPARATIVE STUDY
Bakheet Elsadek, Ahmed Mansour, Tahia Saleem, André Warnecke, Felix Kratz
BACKGROUND: Worldwide, consistent survival benefit for chemotherapy in hepatocellular carcinoma (HCC) is a golden goal for concerned researchers. Nexavar(®) (sorafenib) is the only approved agent that achieved touchable successes in this regard. Thus, there is a pressing medical need for new promising drugs to improve HCC therapy. AIMS: our designed lactosaminated albumin conjugate of doxorubicin (L-HSA-DOXO) that rapidly and preferentially accumulates in the liver is compared, for the first time at its MTD, with doxorubicin and sorafenib, not only for antitumor efficacy but also for overall survival...
February 2017: Digestive and Liver Disease
https://www.readbyqxmd.com/read/27821083/single-administration-of-selective-internal-radiation-therapy-versus-continuous-treatment-with-sorafenib-in-locally-advanced-hepatocellular-carcinoma-sirvenib-study-protocol-for-a-phase-iii-randomized-controlled-trial
#9
Mihir Gandhi, Su Pin Choo, Choon Hua Thng, Say Beng Tan, Albert Su Chong Low, Peng Chung Cheow, Anthony Soon Whatt Goh, Kiang Hiong Tay, Richard Hoau Gong Lo, Brian Kim Poh Goh, Jen San Wong, David Chee Eng Ng, Khee Chee Soo, Wei Ming Liew, Pierce K H Chow
BACKGROUND: Approximately 20 % of hepatocellular carcinoma (HCC) patients diagnosed in the early stages may benefit from potentially curative ablative therapies such as surgical resection, transplantation or radiofrequency ablation. For patients not eligible for such options, prognosis is poor. Sorafenib and Selective Internal Radiation Therapy (SIRT) are clinically proven treatment options in patients with unresectable HCC, and this study aims to assess overall survival following either SIRT or Sorafenib therapy for locally advanced HCC patients...
November 7, 2016: BMC Cancer
https://www.readbyqxmd.com/read/27612422/temozolomide-toxicity-operates-in-a-xct-slc7a11-dependent-manner-and-is-fostered-by-ferroptosis
#10
Tina Sehm, Manfred Rauh, Kurt Wiendieck, Michael Buchfelder, IIker Y Eyüpoglu, Nicolai E Savaskan
The glutamate exchanger xCT (SLC7a11) is causally linked with the malignancy grade of brain tumors and represents a key player in glutamate, cystine and glutathione metabolism. Although blocking xCT is not cytotoxic for brain tumors, xCT inhibition disrupts the neurodegenerative and microenvironment-toxifying activity of gliomas. Here, we report on the use of various xCT inhibitors as single modal drugs and in combination with the autophagy-inducing standard chemotherapeutic agent temozolomide (Temodal/Temcad®, TMZ)...
November 15, 2016: Oncotarget
https://www.readbyqxmd.com/read/27089255/iron-depletion-enhances-the-effect-of-sorafenib-in-hepatocarcinoma
#11
Shinichi Urano, Toshiaki Ohara, Kazuhiro Noma, Ryoichi Katsube, Takayuki Ninomiya, Yasuko Tomono, Hiroshi Tazawa, Shunsuke Kagawa, Yasuhiro Shirakawa, Fumiaki Kimura, Kazuhiro Nouso, Akihiro Matsukawa, Kazuhide Yamamoto, Toshiyoshi Fujiwara
ABSTACT Human hepatocellular carcinoma (HCC) is known to have a poor prognosis. Sorafenib, a molecular targeted drug, is most commonly used for HCC treatment. However, its effect on HCC is limited in clinical use and therefore new strategies regarding sorafenib treatment are required. Iron overload is known to be associated with progression of chronic hepatitis and increased risk of HCC. We previously reported that iron depletion inhibited cancer cell proliferation and conversely induced angiogenesis. Indeed iron depletion therapy including iron chelator needs to be combined with anti-angiogenic drug for its anti-cancer effect...
June 2, 2016: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/27042725/sorafenib-nexavar-and-differentiated-thyroid-cancer-toxic-and-no-proof-of-improved-survival
#12
(no author information available yet)
Radiological progression was delayed by 5 months in one trial, but its design does not allow reliable analysis of survival. Numerous, sometimes serious, adverse effects occurred.
February 2016: Prescrire International
https://www.readbyqxmd.com/read/26709621/improving-oral-bioavailability-of-sorafenib-by-optimizing-the-spring-and-parachute-based-on-molecular-interaction-mechanisms
#13
Chengyu Liu, Zhen Chen, Yuejie Chen, Jia Lu, Yuan Li, Shujing Wang, Guoliang Wu, Feng Qian
Sorafenib is a clinically important oral tyrosine kinase inhibitor for the treatment of various cancers. However, the oral bioavailability of sorafenib tablet (Nexavar) is merely 38-49% relative to the oral solution, due to the low aqueous solubility of sorafenib and its relatively high daily dose. It is desirable to improve the oral bioavailability of sorafenib to expand the therapeutic window, reduce the drug resistance, and enhance patient compliance. In this study, we observed that the solubility of sorafenib could be increased ∼50-fold in the coexistence of poly(vinylpyrrolidone-vinyl acetate) (PVP-VA) and sodium lauryl sulfate (SLS), due to the formation of PVP-VA/SLS complexes at a lower critical aggregation concentration...
February 1, 2016: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/26364606/stamping-out-raf-and-mek1-2-to-inhibit-the-erk1-2-pathway-an-emerging-threat-to-anticancer-therapy
#14
REVIEW
R Mandal, S Becker, K Strebhardt
The RAS-RAF-MEK1/2-ERK1/2 pathway is a key signal transduction pathway in the cells. Critically, it remains constitutively active in approximately 30% of human cancers, having key roles in cancer development, maintenance and progression, while being responsible for poorer prognosis and drug resistance. Consequently, the inhibition of this pathway has been the subject of intense research for >25 years. The advent of better patient screening techniques has increasingly shown that upstream regulators like RAS and RAF remain persistently mutated in many cancer types...
May 19, 2016: Oncogene
https://www.readbyqxmd.com/read/26256994/high-dose-vitamin-c-promotes-regression-of-multiple-pulmonary-metastases-originating-from-hepatocellular-carcinoma
#15
Min-Seok Seo, Ja-Kyung Kim, Jae-Yong Shim
We report a case of regression of multiple pulmonary metastases, which originated from hepatocellular carcinoma after treatment with intravenous administration of high-dose vitamin C. A 74-year-old woman presented to the clinic for her cancer-related symptoms such as general weakness and anorexia. After undergoing initial transarterial chemoembolization (TACE), local recurrence with multiple pulmonary metastases was found. She refused further conventional therapy, including sorafenib tosylate (Nexavar). She did receive high doses of vitamin C (70 g), which were administered into a peripheral vein twice a week for 10 months, and multiple pulmonary metastases were observed to have completely regressed...
September 2015: Yonsei Medical Journal
https://www.readbyqxmd.com/read/26199586/synthesis-characterization-and-anticancer-activity-of-new-metal-complexes-derived-from-2-hydroxy-3-hydroxyimino-4-oxopentan-2-ylidene-benzohydrazide
#16
Abdou Saad El-Tabl, Moshira Mohamed Abd El-Waheed, Mohammed Ahmed Wahba, Nahla Abd El-Halim Abou El-Fadl
Novel metal(II) complexes derived from 2-hydroxy-N'-((Z)-3-(hydroxyimino)-4-oxopentan-2-ylidene)benzohydrazide ligand (H2L) were synthesized and characterized by elemental and thermal analyses (DTA and TGA), IR, UV-VIS, (1)H-NMR, ESR and mass spectroscopy, magnetic susceptibilities, and conductivities measurements. The complexes adopt distorted octahedral geometry. The ESR spectra of the solid copper(II) complexes are characteristic to d(9) configuration and have an axial symmetry type of a d(x (2)-y (2)) ground state...
2015: Bioinorganic Chemistry and Applications
https://www.readbyqxmd.com/read/26112458/aggressive-thyroid-cancer-targeted-therapy-with-sorafenib
#17
REVIEW
Alda Corrado, Silvia M Ferrari, Ugo Politti, Valeria Mazzi, Mario Miccoli, Gabriele Materazzi, Alessandro Antonelli, Salvatore Ulisse, Poupak Fallahi, Paolo Miccoli
Sorafenib (Nexavar), is a multikinase inhibitor, which has demonstrated both antiproliferative and antiangiogenic properties in vitro and in vivo, inhibiting the activity of targets present in the tumoral cells (c-RAF [proto-oncogene serine/threonine-protein kinase], BRAF, (V600E)BRAF, c-KIT, and FMS-like tyrosine kinase 3) and in tumor vessels (c-RAF, vascular endothelial growth factor receptor [VEGFR]-2, VEGFR-3, and platelet-derived growth factor receptor β). Sorafenib was initially approved for the treatment of hepatocellular carcinoma and advanced renal cell carcinoma...
March 2017: Minerva Endocrinologica
https://www.readbyqxmd.com/read/26072416/a-phase-2-open-label-randomized-study-of-pexa-vec-jx-594-administered-by-intratumoral-injection-in-patients-with-unresectable-primary-hepatocellular-carcinoma
#18
RANDOMIZED CONTROLLED TRIAL
Caroline J Breitbach, Anne Moon, James Burke, Tae-Ho Hwang, David H Kirn
Primary liver cancer (hepatocellular carcinoma; HCC) in patients not eligible for surgery or transplant is currently treated by locoregional therapeutic approaches, including trans-arterial chemoembolization and radiofrequency ablation. Sorafenib (Nexavar; Bayer/Onyx) is currently the only approved systemic therapy for patients having failed locoregional interventions. Oncolytic viruses are designed to selectively replicate within, and subsequently lyse, cancer cells by a unique mechanisms-of-action that is not cross-resistant with approved therapies (Kirn et al...
2015: Methods in Molecular Biology
https://www.readbyqxmd.com/read/25858032/grp78-dna-k-is-a-target-for-nexavar-stivarga-votrient-in-the-treatment-of-human-malignancies-viral-infections-and-bacterial-diseases
#19
Jane L Roberts, Mehrad Tavallai, Aida Nourbakhsh, Abigail Fidanza, Tanya Cruz-Luna, Elizabeth Smith, Paul Siembida, Pascale Plamondon, Kelly A Cycon, Christopher D Doern, Laurence Booth, Paul Dent
Prior tumor cell studies have shown that the drugs sorafenib (Nexavar) and regorafenib (Stivarga) reduce expression of the chaperone GRP78. Sorafenib/regorafenib and the multi-kinase inhibitor pazopanib (Votrient) interacted with sildenafil (Viagra) to further rapidly reduce GRP78 levels in eukaryotes and as single agents to reduce Dna K levels in prokaryotes. Similar data were obtained in tumor cells in vitro and in drug-treated mice for: HSP70, mitochondrial HSP70, HSP60, HSP56, HSP40, HSP10, and cyclophilin A...
October 2015: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/25742918/sorafenib-a-review-of-its-use-in-patients-with-radioactive-iodine-refractory-metastatic-differentiated-thyroid-carcinoma
#20
REVIEW
Hannah A Blair, Greg L Plosker
Sorafenib (Nexavar®) is the first tyrosine kinase inhibitor to be approved for the treatment of radioactive iodine (RAI)-refractory differentiated thyroid carcinoma (DTC). In the pivotal phase III DECISION trial in patients with RAI-refractory, locally advanced or metastatic DTC, oral sorafenib 400 mg twice daily significantly prolonged median progression-free survival (PFS) relative to placebo. The PFS benefit of sorafenib over placebo was evident in all pre-specified clinical and genetic biomarker subgroups, and neither BRAF nor RAS mutation status was predictive of sorafenib benefit for PFS...
March 2015: Targeted Oncology
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