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https://www.readbyqxmd.com/read/29673151/tumor-molecular-profiling-for-an-individualized-approach-to-the-treatment-of-hepatocellular-carcinoma-a-patient-case-study
#1
Kristine Posadas, Anita Ankola, Zhaohai Yang, Nelson S Yee
Hepatocellular carcinoma (HCC) is increasing in incidence, and the associated mortality rate remains among the highest. For advanced HCC, sorafenib has been shown to slightly prolong survival, and regorafenib and nivolumab, both recently approved by the United States Food and Drug Administration (FDA), may produce clinical benefits to a limited extent. Systemic chemotherapy has been shown to produce a modest response, but there is no clinically valid biomarker that can be used to predict which patients may benefit...
April 17, 2018: Biomedicines
https://www.readbyqxmd.com/read/29673031/fragmentation-pathways-and-differentiation-of-positional-isomers-of-sorafenib-and-structural-analogues-by-esi-it-ms-n-and-esi-q-tof-ms-ms-coupled-with-dft-calculations
#2
Dandan Yu, Xianrui Liang
Sorafenib is an orally active multikinase inhibitor for the treatment of renal cell carcinoma. A series of sorafenib structural analogues were investigated in this work for their gas-phase fragmesntation behaviors using electrospray ionization ion trap mass spectrometry and quadrupole time-of-flight mass spectrometry in the positive mode. The possible fragmentation pathways were proposed based on ESI-MS/MS data and theoretical calculation. Different from the typical α-cleavage of amide, consecutive reactions that involved elimination of H2 O and CH3 NC were observed for 2-pyridinecarboxamide derivatives, which were followed by the formation of a stabilized seven-member ring carbocation by loss of CO...
April 19, 2018: Journal of Mass Spectrometry: JMS
https://www.readbyqxmd.com/read/29670787/radiation-recall-dermatitis-in-patients-treated-with-sorafenib
#3
Keyur Mehta, Andreas Kaubisch, Justin Tang, Aneesh Pirlamarla, Shalom Kalnicki
Introduction: Radiation recall dermatitis (RRD) is a phenomenon that occurs in previously irradiated areas shortly after administration of a chemotherapeutic agent. As the use of sorafenib expands, the incidence of radiation recall dermatitis induced by sorafenib will likely increase. Here, we report on a patient who developed RRD and describe his clinical characteristics along with a review of the literature. Case Presentation: Our patient was treated with palliative radiation therapy (RT) to a painful metastatic hepatocellular carcinoma lesion in the right forearm...
2018: Case Reports in Oncological Medicine
https://www.readbyqxmd.com/read/29670046/resistance-to-anti-angiogenic-therapy-in-cancer-alterations-to-anti-vegf-pathway
#4
REVIEW
Yoshiro Itatani, Kenji Kawada, Takamasa Yamamoto, Yoshiharu Sakai
Anti-angiogenic therapy is one of the promising strategies for many types of solid cancers. Bevacizumab (Avastin), a recombinant humanized monoclonal antibody of vascular endothelial growth factor (VEGF) A, was approved for the first time as an anti-angiogenic drug for the treatment of metastatic colorectal cancer (CRC) by the Food and Drug Administration (FDA) in 2004. In addition, the other VEGF pathway inhibitors including small molecule tyrosine kinase inhibitors (sunitinib, sorafenib, and pazopanib), a soluble VEGF decoy receptor (aflibercept), and a humanized monoclonal antibody of VEGF receptor 2 (VEGFR2) (ramucirumab) have been approved for cancer therapy...
April 18, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29669553/significant-response-to-nivolumab-for-metastatic-chromophobe-renal-cell-carcinoma-with-sarcomatoid-differentiation-a-case-report
#5
Go Noguchi, Sohgo Tsutsumi, Masato Yasui, Shinji Ohtake, Susumu Umemoto, Noboru Nakaigawa, Masahiro Yao, Takeshi Kishida
BACKGROUND: The treatment of advanced or metastatic renal cell carcinoma (RCC) has drastically changed since the approval of immune checkpoint therapy. Nivolumab is a treatment option for patients with metastatic RCC, previously treated with targeted antiangiogenic therapy. The efficacy of nivolumab for patients with RCC was established by the Checkmate 025 clinical trial. Chromophobe RCC (CRCC) represents around 5% of RCC cases, but non-clear cell RCC (non-ccRCC) subtypes were excluded from the Checkmate 025 clinical trial...
April 18, 2018: BMC Urology
https://www.readbyqxmd.com/read/29665898/-clinical-characteristics-and-prognosis-of-acute-myeloid-leukemia-with-flt3-itd-mutation
#6
Yan Liu, Xiao-Yan Ke, Jing Wang, Ji-Jun Wang, Hong-Mei Jing, Fei Dong
OBJECTIVE: To investigate the clinical characteristics of acute myeloid leukemia(AML) patients with FLT3-ITD(Fms-like tyrosine kinase3, intenal tandem duplication) mutation and their response to treatment. METHODS: Retrospective analysis of 128 newly diagnosed AML (except type M3) patients was performed between January 2014 and July 2017. Patients were divided into FLT3-ITD mutated group and non-mutated group. Mutation detection was carried out by using polymerase chain reaction(PCR) and gene sequencing analysis...
April 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/29665121/homoharringtonine-could-induce-quick-protein-synthesis-of-psmd11-through-activating-mek1-erk1-2-signaling-pathway-in-pancreatic-cancer-cells
#7
Lele Wang, Linlin Zhao, Guo Wei, Dieter Saur, Barbara Seidler, Junyan Wang, Chuanxin Wang, Tonggang Qi
Pancreatic ductal adenocarcinoma (PDAC) remains one of the most devastating disease with the 5-year survival rate less than 6%. In this study, we investigated if inhibiting protein synthesis directly with homoharringtonine (HHT) could induce acute apoptosis in pancreatic cancer cells through quick depletion of multiple short-lived critical members of the central proteome, example, PSMD11(26S proteasome non-ATPase regulatory subunit 11). It was shown that although HHT could inhibit proliferation and growth of MiaPaCa-2 and PANC-1 cells in a time- and dose-dependent manner, only part of pancreatic cancer cells could be induced to die through acute apoptosis...
April 17, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29663896/molecular-interaction-and-computational-analytical-studies-of-pinocembrin-for-its-antiangiogenic-potential-targeting-vegfr-2-a-persuader-of-metastasis
#8
Neha Sharma, Mala Sharma, Eram Shakeel, Qazi M Sajid Jamal, Mohammad A Kamal, Usman Sayeed, Mohammad K A Khan, Mohammad H Siddiqui, Jamal M Arif, Salman Akhtar
BACKGROUND: Designing a novel antagonist against VEGFR-2 is being applied currently to inhibit cancer growth and metastasis. Because of the unexpected side effects incurred by the contemporary anticancer medications, the focus has been laid towards identifying natural compounds that might carry the potential to inhibit tumor progression. VEGR-2 remains an important target for anticancer drug development as it is the master regulator of vascular growth. OBJECTIVE: The study focuses on virtual screening of compounds from plants of Asteraceae family that bears antiangiogenic potential and thus, inhibiting VEGFR-2 using a computational approach...
April 16, 2018: Medicinal Chemistry
https://www.readbyqxmd.com/read/29661222/platelet-rich-plasma-enhances-the-proliferation-of-human-adipose-stem-cells-through-multiple-signaling-pathways
#9
Fangyuan Lai, Natsuko Kakudo, Naoki Morimoto, Shigeru Taketani, Tomoya Hara, Takeshi Ogawa, Kenji Kusumoto
BACKGROUND: Platelet-rich plasma (PRP) is an autologous blood product that contains a high concentration of several growth factors. Platelet-derived growth factor (PDGF)-BB is a potential mitogen for human adipose-derived stem cells (hASCs). PRP stimulates proliferation of hASCs; however, the signaling pathways activated by PRP remain unclear. METHODS: hASCs were cultured with or without PRP or PDGF-BB, and proliferation was assessed. hASCs were also treated with PRP or PDGF-BB with or without imatinib, which is a PDGF receptor tyrosine kinase inhibitor, or sorafenib, which is a multikinase inhibitor...
April 16, 2018: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29659672/adi-peg-20-plus-best-supportive-care-versus-placebo-plus-best-supportive-care-in-patients-with-advanced-hepatocellular-carcinoma
#10
G Abou-Alfa, S Qin, B-Y Ryoo, S-N Lu, C-J Yen, Y-H Feng, H Y Lim, F Izzo, M Colombo, D Sarker, L Bolondi, G Vaccaro, W P Harris, Z Chen, R A Hubner, T Meyer, W Sun, J J Harding, E M Hollywood, J Ma, P J Wan, M Ly, J Bomalaski, A Johnston, C-C Lin, Y Chao, L-T Chen
Background: Arginine depletion is a putative target in hepatocellular carcinoma (HCC). HCC often lacks argininosuccinate synthetase, a citrulline to arginine-repleting enzyme. ADI-PEG 20 is a cloned arginine degrading enzyme - arginine deiminase - conjugated with polyethylene glycol. The goal of this study was to evaluate this agent as a potential novel therapeutic for HCC after first line systemic therapy. Methods and Patients: Patients with histologically proven advanced HCC and Child-Pugh up to B7 with prior systemic therapy, were randomized 2:1 to ADI-PEG 20 18 mg/m2 vs...
April 5, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29658816/a-mixed-treatment-comparison-of-toxicity-of-gemcitabine-combined-with-different-targeted-drugs-in-the-treatment-of-advanced-or-metastatic-pancreatic-cancer
#11
Penpa Dorjee, Zi-Wen Long
The mixed treatment comparison study was performed in order to compare the toxicities of Gemcitabine and different targeted drug combinations in the treatment of advanced/metastatic pancreatic cancer (PC). Searches were performed from the inception of PubMed and Cochrane Library databases to February 2017. This study included randomized controlled trials (RCTs) of Gemcitabine and different targeted drug combinations in the treatment of advanced/metastatic PC. Odds ratio (OR) values were calculated by direct and indirect comparisons, and the surface under the cumulative ranking curves (SUCRA) were drawn...
April 16, 2018: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/29657088/monocarboxylate-transporters-mct1-and-mct4-are-independent-prognostic-biomarkers-for-the-survival-of-patients-with-clear-cell-renal-cell-carcinoma-and-those-receiving-therapy-targeting-angiogenesis
#12
Yan-Wei Cao, Yong Liu, Zhen Dong, Lei Guo, En-Hao Kang, Yong-Hua Wang, Wei Zhang, Hai-Tao Niu
BACKGROUND: Prognostic biomarkers for patients with clear cell renal cell carcinoma (ccRCC), particularly those receiving therapy targeting angiogenesis, are not well established. In this study, we examined the correlations of monocarboxylate transporter 1 (MCT1) and MCT4, 2 critical transporters for glycolytic metabolism, with various clinicopathological parameters as well as survival of patients with ccRCC and those treated with vascular endothelial growth factor receptor (VEGFR) inhibitors...
April 12, 2018: Urologic Oncology
https://www.readbyqxmd.com/read/29655795/enhanced-oral-absorption-of-sorafenib-via-the-layer-by-layer-deposition-of-a-ph-sensitive-polymer-and-glycol-chitosan-on-the-liposome
#13
Mengjia Zhao, Sang Hoon Lee, Jae Geun Song, Hyeon Young Kim, Hyo-Kyung Han
This study aimed to design the effective formulation of sorafenib (SF) to enhance the oral drug absorption. Three liposomal formulations of SF were prepared including uncoated liposome (SF-Lip), glycol chitosan-coated liposome (GC-SF-Lip), and Eudragit S100-glycol-chitosan coated liposome (SGC-SF-Lip). All formulations showed a narrow size distribution with a high encapsulation efficiency. Both GC-SF-Lip and SGC-SF-Lip exhibited good stability at acidic and neutral pHs without any significant drug leakage, while SF-Lip appeared to be unstable at pH 1...
April 12, 2018: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/29651967/design-synthesis-in-vitro-anti-cancer-activity-admet-profile-and-molecular-docking-of-novel-triazolo-3-4-a-phthalazine-derivatives-targeting-vegfr-2-enzyme
#14
Khaled El-Adl, Abdel-Ghany A El-Helby, Rezk R A Ayyad, Helmy Sakr, Mamdouh M Ali, Fathalla Khedr
In view of their expected anticancer activity, novel triazolo[3,4-a]phthalazine derivatives 5-6a-o and 3-substituted-bis([1,2,4]triazolo)[3,4-a:4',3'-c]phthalazines 9a-b were designed, synthesized and evaluated for their anti-proliferative activity against two human tumor cell lines HCT-116 human colon adenocarcinoma and MCF-7 breast cancer. It was found that, compound 6o the most potent derivative against both HCT116 and MCF-7 cancer cell lines. Compounds 6o, 6m, 6d and 9b showed the highest anticancer activities against HCT116 human colon adenocarcinoma with IC50 of 7±0...
April 12, 2018: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/29650821/-continuation-of-axitinib-for-advanced-renal-cell-carcinoma-by-the-application-of-homecare-urology-a-case-report-and-literature-review
#15
Satoshi Yazawa, Yuji Kato, Jin Nakahara, Toshio Miyata, Mototsugu Oya
A 56-year-old man with advanced RCC and a past medical history of type 2 diabetes underwent a radical left nephrectomy following a histological diagnosis of papillary RCC, G2, INF b, pT3, V1 in 1999. In 2008, sorafenib was started to treat multiple pulmonary metastases of RCC. In 2011, sorafenib was switched to sunitinib when radiologic progression was observed. In 2014, sunitinib was switched to axitinib when further radiologic progression was observed. In 2015, the patient was referred to Yazawa clinic for homecare urology when hospital visits became difficult due to cancer pain and bilateral lower-extremity muscle weakness...
April 2018: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/29645345/comparison-of-clinical-outcome-of-hepatic-arterial-infusion-chemotherapy-and-sorafenib-for-advanced-hepatocellular-carcinoma-according-to-macrovascular-invasion-and-transcatheter-arterial-chemoembolization-refractory-status
#16
Kenichiro Kodama, Tomokazu Kawaoka, Hiroshi Aikata, Shinsuke Uchikawa, 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, Kazuaki Chayama
AIM: Sorafenib is the standard treatment for patients with advanced hepatocellular carcinoma (HCC) with distant metastasis, unresectable HCC, and HCC refractory to transcatheter arterial chemoembolization (TACE) or with macroscopic vascular invasion (MVI). Also, hepatic arterial infusion chemotherapy (HAIC) has been used for advanced HCC in Southeast and East Asian countries. However, clearer information is needed for choosing appropriately between these therapies. METHODS: The subjects were 391 HAIC and 431 sorafenibs administered at our hospital and related hospitals...
April 12, 2018: Journal of Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/29629806/comparative-effectiveness-of-transarterial-embolization-and-sorafenib-for-hepatocellular-carcinoma-a-population-based-study
#17
Sharon W Kwan, William P Harris, Laura S Gold, Paul L Hebert
OBJECTIVE: The purpose of this study was to compare the clinical effectiveness of embolization with that of sorafenib in the management of hepatocellular carcinoma as practiced in real-world settings. MATERIALS AND METHODS: This population-based observational study was conducted with the Surveillance, Epidemiology, and End Results-Medicare linked database. Patients 65 years old and older with a diagnosis of primary liver cancer between 2007 and 2011 who underwent embolization or sorafenib treatment were identified...
April 9, 2018: AJR. American Journal of Roentgenology
https://www.readbyqxmd.com/read/29628325/novel-thioureido-benzenesulfonamide-derivatives-with-enaminone-linker-as-potent-anticancer-radiosensitizers-and-vegfr2-inhibitors
#18
Mostafa M Ghorab, Fatma A Ragab, Helmy I Heiba, Marwa G El-Gazzar, Mostafa G M El-Gazzar
In this study, novel series of thioureido-benzenesulfonamide derivatives bearing an enaminone linker either meta or para oriented and having terminal linear or substituted aromatic or heteroaromatic ring system 5-16a,b were designed and synthesized based on the general pharmacophoric features of type II VEGFR2 inhibitors. Evaluation of the synthesized compounds against HEPG2 hepatocellular carcinoma cells in vitro identified compounds 5b, 6b and 10-13b as most active anticancer agents with IC50 equal to 0.12, 0...
March 31, 2018: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29625879/tivantinib-for-second-line-treatment-of-met-high-advanced-hepatocellular-carcinoma-metiv-hcc-a-final-analysis-of-a-phase-3-randomised-placebo-controlled-study
#19
Lorenza Rimassa, Eric Assenat, Markus Peck-Radosavljevic, Marc Pracht, Vittorina Zagonel, Philippe Mathurin, Elena Rota Caremoli, Camillo Porta, Bruno Daniele, Luigi Bolondi, Vincenzo Mazzaferro, William Harris, Nevena Damjanov, Davide Pastorelli, María Reig, Jennifer Knox, Francesca Negri, Jörg Trojan, Carlos López López, Nicola Personeni, Thomas Decaens, Marie Dupuy, Wolfgang Sieghart, Giovanni Abbadessa, Brian Schwartz, Maria Lamar, Terri Goldberg, Dale Shuster, Armando Santoro, Jordi Bruix
BACKGROUND: Tivantinib (ARQ 197), a selective, oral MET inhibitor, improved overall survival and progression-free survival compared with placebo in a randomised phase 2 study in patients with high MET expression (MET-high) hepatocellular carcinoma previously treated with sorafenib. The aim of this phase 3 study was to confirm the results of the phase 2 trial. METHODS: We did a phase 3, randomised, double-blind, placebo-controlled study in 90 centres in Australia, the Americas, Europe, and New Zealand...
April 3, 2018: Lancet Oncology
https://www.readbyqxmd.com/read/29625271/tyrosine-kinase-inhibition-effects-of-novel-pyrazolo-1-5-a-pyrimidines-and-pyrido-2-3-d-pyrimidines-ligand-synthesis-biological-screening-and-molecular-modeling-studies
#20
Mardia T El Sayed, Hoda A R Hussein, Nora M Elebiary, Ghada S Hassan, Shahenda M Elmessery, Ahmed R Elsheakh, Mohamed Nayel, Hatem A Abdel-Aziz
Tyrosine kinases are one of the most critical mediators in the signaling path way. Late studies have proved the part of tyrosine kinases in the pathophysiology of cancer diseases. This current research paper has focused on investigating the novel Pyrazolo[1,5-a]pyrimidines and Pyrido[2,3-d]pyrimidines as a small molecules that can inhibit tyrosine kinase in cancer cells. NCI protocol was applied to test the antitumor activity of such compounds. Leukemia and renal cancer cell lines proved to be sensitive to some derivatives such as 6b-d, 9a and 11 with GI% values ranging from 30...
March 26, 2018: Bioorganic Chemistry
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