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Sorafenib

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https://www.readbyqxmd.com/read/29040999/hepatic-function-during-repeated-tace-procedures-and-prognosis-after-introducing-sorafenib-in-patients-with-unresectable-hepatocellular-carcinoma-multicenter-analysis
#1
Atsushi Hiraoka, Takashi Kumada, Masatoshi Kudo, Masashi Hirooka, Yohei Koizumi, Yoichi Hiasa, Kazuto Tajiri, Hidenori Toyoda, Toshifumi Tada, Hironori Ochi, Koji Joko, Noritomo Shimada, Akihiro Deguchi, Toru Ishikawa, Michitaka Imai, Kunihiko Tsuji, Kojiro Michitaka
BACKGROUND/AIM: We evaluated the relationship of hepatic function with repeated transarterial catheter chemoembolization (TACE) and prognosis after sorafenib treatment in various patient cohorts. METHODS: Study 1 comprised of 212 Barcelona clinic liver cancer stage-B (BCLC-B) HCC patients classified as Child-Pugh A (CP-A) and who had received repeated TACE treatments (r-TACE) (naïve:recurrence = 66:146). Study 2 comprised of 435 patients with unresectable HCC classified as CP-A in who sorafenib was introduced (naïve:recurrence = 37:398; CP score 5:6 = 282:153; macro-vessel invasion [MVI]+: extrahepatic metastasis [EHM]+ both negative = 124:226:143)...
2017: Digestive Diseases
https://www.readbyqxmd.com/read/29040994/sorafenib-regorafenib-sequential-therapy-in-advanced-hepatocellular-carcinoma-a-single-institute-experience
#2
Kazuomi Ueshima, Naoshi Nishida, Masatoshi Kudo
OBJECTIVES: Previously, no therapeutic agent has been known to improve the overall survival compared with placebo in patients with hepatocellular carcinoma (HCC), who have progressed after sorafenib. In this patient population, regorafenib was first demonstrated to confer a survival benefit in the RESORCE trial, and subsequently it was approved as a second-line treatment for patients with advanced HCC. An open-label expanded access program (EAP) of regorafenib was implemented for compassionate use...
2017: Digestive Diseases
https://www.readbyqxmd.com/read/29037022/radiation-recall-dermatitis-triggered-by-sorafenib-after-radiation-therapy-for-hepatocellular-carcinoma
#3
Gwi Eon Kim, Hee-Sung Song, Ki Jung Ahn, Young Suk Kim
Sorafenib is widely used for unresectable and metastatic hepatocellular carcinomas. Radiation recall dermatitis (RRD) is an acute inflammatory reaction confined to previously irradiated skin that occurs after the administration of certain drugs. RRD after sorafenib treatment is rare; five cases have been reported thus far. We describe a 44-year-old man irradiated for chest wall bone metastasis from hepatocellular carcinoma. Eight days after radiotherapy completion, systemic therapy for metastatic hepatocellular carcinoma was initiated with sorafenib treatment...
September 2017: Radiation Oncology Journal
https://www.readbyqxmd.com/read/29036035/the-treatment-path-in-hepatocellular-carcinoma
#4
Hashem B El-Serag, Andrew X Zhu, Matthew S Johnson
The treatment approach for hepatocellular carcinoma (HCC) depends on the stage and extent of disease, the severity of the underlying liver disease, and the overall performance status of the patient. Treatment consists of 4 main strategies: surgery (eg, resection and liver transplant), locoregional procedures (eg, ablation and transarterial embolization), systemic therapies, and best supportive care. For patients with early-stage tumors, surgical treatment or ablation can be curative. Patients with intermediate-stage disease can be candidates for embolization, administered as either transarterial chemoembolization (TACE) or transarterial radioembolization (TARE)...
August 2017: Clinical Advances in Hematology & Oncology: H&O
https://www.readbyqxmd.com/read/29035731/postoperative-adjuvant-sorafenib-or-sunitinib-for-nonmetastatic-renal-cell-carcinoma-with-venous-tumor-thrombus-a-prospective-cohort-study
#5
Liangyou Gu, Hongzhao Li, Luyao Chen, Xintao Li, Baojun Wang, Qingbo Huang, Fan Zhang, Yang Fan, Yu Gao, Cheng Peng, Xin Ma, Xu Zhang
PURPOSE: To evaluate the efficacy and safety of antiangiogenic agents (sorafenib and sunitinib) as postoperative adjuvant therapy in patients with nonmetastatic renal cell carcinoma (RCC) and venous tumor thrombus (VTT). MATERIAL AND METHODS: From March 2006 to January 2016, 147 patients who met the inclusion criteria were enrolled; 27 patients received sorafenib, and 17 patients received sunitinib. After radical nephrectomy and thrombectomy, the duration of maintenance targeted medication treatment was approximately 1 year...
October 13, 2017: Translational Oncology
https://www.readbyqxmd.com/read/29035381/high-expression-of-hoxa13-correlates-with-poorly-differentiated-hepatocellular-carcinomas-and-modulates-sorafenib-response-in-in-vitro-models
#6
Luca Quagliata, Cristina Quintavalle, Manuela Lanzafame, Matthias S Matter, Chiara Novello, Luca di Tommaso, Tiziana Pressiani, Lorenza Rimassa, Luigi Tornillo, Massimo Roncalli, Clemente Cillo, Pierlorenzo Pallante, Salvatore Piscuoglio, Charlotte Ky Ng, Luigi M Terracciano
Hepatocellular carcinoma (HCC) represents the fifth and ninth cause of mortality among male and female cancer patients, respectively and typically arises on a background of a cirrhotic liver. HCC develops in a multi-step process, often encompassing chronic liver injury, steatosis and cirrhosis eventually leading to the malignant transformation of hepatocytes. Aberrant expression of the class I homeobox gene family (HOX), a group of genes crucial in embryogenesis, has been reported in a variety of malignancies including solid tumors...
October 16, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29034773/substrate-dependent-effects-of-molecular-targeted-anticancer-agents-on-activity-of-organic-anion-transporting-polypeptide-1b1
#7
Hiroyoshi Koide, Masayuki Tsujimoto, Ai Takeuchi, Miyu Tanaka, Yoko Ikegami, Mayu Tagami, Syoko Abe, Miki Hashimoto, Tetsuya Minegaki, Kohshi Nishiguchi
1. Organic anion-transporting polypeptide 1B1 (OATP1B1) plays an important role in the hepatic uptake of a broad range of substrate drugs. In vitro experiments show that molecular-targeted agents do not always have similar effects on OATP1B1 activity. 2. The purpose of this study was to clarify whether the effects of molecular-targeted agents on OATP1B1 are substrate-dependent. We used OATP1B1-transfected cells to compare the effects of molecular-targeted agents on OATP1B1-mediated uptake of fluorescein (FL), 2',7'-dichlorofluorescein (DCF), atorvastatin, SN-38, and valsartan...
October 16, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/29034366/a-phase-2-study-incorporating-sorafenib-into-the-chemotherapy-for-older-adults-with-flt3-mutated-acute-myeloid-leukemia-calgb-11001
#8
Geoffrey L Uy, Sumithra J Mandrekar, Kristina Laumann, Guido Marcucci, Weiqiang Zhao, Mark J Levis, Heidi D Klepin, Maria R Baer, Bayard L Powell, Peter Westervelt, Daniel J DeAngelo, Wendy Stock, Ben Sanford, William G Blum, Clara D Bloomfield, Richard M Stone, Richard A Larson
The Cancer and Leukemia Group B (CALGB), now part of the Alliance for Clinical Trials in Oncology, conducted a multicenter, single-arm, phase 2 study in patients ≥60 years with FMS-like tyrosine kinase 3 (FLT3)-mutated acute myeloid leukemia (AML). In this study, sorafenib was added to daunorubicin and cytarabine-based induction and consolidation chemotherapy and was also continued for 12 months of maintenance therapy. The primary end point of the study was overall survival (OS) at 1 year in the FLT3 internal tandem duplication (FLT3-ITD) cohort...
January 24, 2017: Blood Advances
https://www.readbyqxmd.com/read/29033791/protein-synthesis-inhibition-and-activation-of-the-c-jun-n-terminal-kinase-are-potential-contributors-to-cisplatin-ototoxicity
#9
Brian D Nicholas, Shimon Francis, Elizabeth L Wagner, Sibo Zhang, Jung-Bum Shin
Cisplatin has been regarded as an effective and versatile chemotherapeutic agent for nearly 40 years. Though the associated dose-dependent ototoxicity is known, the cellular mechanisms by which cochleovestibular hair cell death occur are not well understood. We have previously shown that aminoglycoside ototoxicity is mediated in part by cytosolic protein synthesis inhibition. Despite a lack of molecular similarity, aminoglycosides were shown to elicit similar stress pathways to cisplatin. We therefore reasoned that there may be some role of protein synthesis inhibition in cisplatin ototoxicity...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29033542/axitinib-in-the-treatment-of-renal-cell-carcinoma-design-development-and-place-in-therapy
#10
REVIEW
Audrey Bellesoeur, Edith Carton, Jerome Alexandre, Francois Goldwasser, Olivier Huillard
Since 2005, the approved first-line treatment of metastatic renal cell carcinoma consists in tyrosine kinase inhibitors (TKIs) targeting the vascular endothelial growth factor receptors (VEGFRs). Axitinib is an oral second-generation TKI and a potent VEGFR inhibitor with a half maximal inhibitory concentration for the VEGF family receptors 10-fold lower than other TKIs. Axitinib activity in renal cell carcinoma (RCC) patients has been studied in various settings and particularly as second-line treatment. In this setting, axitinib with clinically based dose escalation compared to sorafenib has demonstrated an improvement in progression-free survival in a randomized Phase III trial leading to US Food and Drug Administration approval...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/29030911/phosphorylated-erk-is-a-potential-prognostic-biomarker-for-sorafenib-response-in-hepatocellular-carcinoma
#11
Yuelong Liang, Jiang Chen, Qingsong Yu, Tong Ji, Bin Zhang, Junjie Xu, Yi Dai, Yangyang Xie, Hui Lin, Xiao Liang, Xiujun Cai
Sorafenib, the only approved drug for hepatocellular carcinoma, acts as a remarkable inhibitor of Raf serine-threonine kinases. However, Sorafenib is expensive, and clinical experience shows that it is not an effective treatment for many patients. Previous study has demonstrated that phosphorylated ERK (pERK) is a key downstream component in the RAF/MEK/ERK signaling pathway. Here, we investigate whether pERK is a useful biomarker for treating HCC with Sorafenib. In vitro cell viability assays showed that the efficacy of Sorafenib was distinctly different according to the level of pERK...
October 13, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/29029548/antiangiogenic-agents-after-first-line-and-sorafenib-plus-chemoembolization-a-systematic-review
#12
REVIEW
Andrea Casadei Gardini, Daniele Santini, Giuseppe Aprile, Nicola Silvestris, Emanuele Felli, Francesco Giuseppe Foschi, Giorgio Ercolani, Giorgia Marisi, Martina Valgiusti, Alessandro Passardi, Marco Puzzoni, Marianna Silletta, Oronzo Brunetti, Giovanni Gerardo Cardellino, Giovanni Luca Frassineti, Mario Scartozzi
Transarterial chemoembolization (TACE) is the standard treatment for intermediate stage, although the combination of TACE with sorafenib may theoretically benefit HCC patients in intermediate stage. Owing to the significant antiangiogenic effect of sorafenib and the limitation of TACE, it is rational to combine them. Though the strategy of combining TACE and sorafenib has been increasingly used in patients with unresectable HCC but the current evidence is controversial and its clinical role has not been determined yet...
September 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29029413/targeting-shp-1-stat3-signaling-a-promising-therapeutic-approach-for-the-treatment-of-cholangiocarcinoma
#13
Ming-Hung Hu, Li-Ju Chen, Yen-Lin Chen, Ming-Shen Tsai, Chung-Wai Shiau, Tzu-I Chao, Chun-Yu Liu, Jia-Horng Kao, Kuen-Feng Chen
Sorafenib is a multiple kinase inhibitor which targets Raf kinases, VEGFR, and PDGFR and is approved for the treatment of hepatocellular carcinoma (HCC). Previously, we found that p-STAT3 is a major target of SC-43, a sorafenib derivative. In this study, we report that SC-43-induced apoptosis in cholangiocarcinoma (CCA) via a novel mechanism. Three CCA cell lines (HuCCT-1, KKU-100 and CGCCA) were treated with SC-43 to determine their sensitivity to SC-43-induced cell death and apoptosis. We found that SC-43 activated SH2 domain-containing phosphatase 1 (SHP-1) activity, leading to p-STAT3 and downstream cyclin B1 and Cdc2 downregulation, which induced G2-M arrest and apoptotic cell death...
September 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29026704/therapeutic-inhibitors-against-mutated-braf-and-mek-for-the-treatment-of-metastatic-melanoma
#14
REVIEW
Sunhyo Ryu, Chakyung Youn, Ae Ran Moon, Amanda Howland, Cheryl A Armstrong, Peter I Song
Melanoma is one of the most aggressive cancers in the world and is responsible for the majority of skin cancer deaths. Recent advances in the field of immunotherapy using active, adoptive, and antigen-specific therapeutic approaches, have generated the expectation that these technologies have the potential to improve the treatment of advanced malignancies, including melanoma. Treatment options for metastatic melanoma patients have been dramatically improved by the FDA approval of new therapeutic agents including vemurafenib, dabrafenib, and sorafenib...
September 2017: Chonnam Medical Journal
https://www.readbyqxmd.com/read/29023959/pembrolizumab-for-metastatic-hepatocellular-carcinoma-following-live-donor-liver-transplantation-the-silver-bullet
#15
A Rammohan, M S Reddy, M Farouk, J Vargese, M Rela
Therapeutic options for extrahepatic metastases following Liver Transplantation(LT) for Hepatocellular carcinoma(HCC) are limited, and the prognosis remains poor. Innovative blockade of immune checkpoints, such as monoclonal antibodies against programmed death receptor 1 have shown promise in the treatment of solid organ malignancies. Here, we report a case of metastatic HCC after LT, where Pembrolizumab was started following a poor response with Sorafenib. There was a complete radiological response to the drug with no liver graft rejection or dysfunction...
October 10, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29022906/increasing-ar-by-hif-2%C3%AE-inhibitor-pt-2385-overcomes-the-side-effects-of-sorafenib-by-suppressing-hepatocellular-carcinoma-invasion-via-alteration-of-pstat3-pakt-and-perk-signals
#16
Junjie Xu, Longbo Zheng, Jiang Chen, Yin Sun, Hui Lin, Ren-An Jin, Minyue Tang, Xiao Liang, Xiujun Cai
Although sorafenib is currently used as a standard treatment for advanced hepatocellular carcinoma, low response rate, transient and limited efficacy, primary and acquired resistance and negative side-effects gain increasing attentions, suggesting the need for better efficacious combination therapy. Here, we demonstrated that the sorafenib-induced or hypoxia-induced hypoxia inducible factor (HIF)-2α could bind to an hypoxia responsive element within 500 bp region of androgen receptor (AR) promoter and thus transcriptionally suppress AR...
October 12, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/29021381/activation-of-fak-and-src-mediates-acquired-sorafenib-resistance-in-a549-human-lung-adenocarcinoma-xenografts
#17
Qingyu S Zhou, Xiaofang Guo, Riya Choksi
Despite encouraging clinical results with sorafenib monotherapy in patients with KRAS-mutant non-small cell lung cancer (NSCLC), the overall survival benefit of this drug is limited by the inevitable development of acquired resistance. The exact mechanism underlying acquired sorafenib resistance in KRAS-mutant NSCLC is unclear. In this study, the mechanism of acquired sorafenib resistance was explored using a biologically relevant xenograft model, which was established by using the A549 human lung adenocarcinoma cell line and an in-vivo derived sorafenib-resistant A549 subline (A549/SRFres)...
October 11, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29016627/cost-effectiveness-analysis-of-treatment-with-non-curative-or-palliative-intent-for-hepatocellular-carcinoma-in-the-real-world-setting
#18
Hla-Hla Thein, Yao Qiao, Ahmad Zaheen, Nathaniel Jembere, Gonzalo Sapisochin, Kelvin K W Chan, Eric M Yoshida, Craig C Earle
Hepatocellular carcinoma (HCC) presentation is heterogeneous necessitating a variety of therapeutic interventions with varying efficacies and associated prognoses. Poor prognostic patients often undergo non-curative palliative interventions including transarterial chemoembolization (TACE), sorafenib, chemotherapy, or purely supportive care. The decision to pursue one of many palliative interventions for HCC is complex and an economic evaluation comparing these interventions has not been done. This study evaluates the cost-effectiveness of non-curative palliative treatment strategies such as TACE alone or TACE+sorafenib, sorafenib alone, and non-sorafenib chemotherapy compared with no treatment or best supportive care (BSC) among patients diagnosed with HCC between 2007 and 2010 in a Canadian setting...
2017: PloS One
https://www.readbyqxmd.com/read/28992881/cost-effectiveness-analysis-of-transcatheter-arterial-chemoembolization-with-or-without-sorafenib-for-the-treatment-of-unresectable-hepatocellular-carcinoma
#19
Rong-Ce Zhao, Jing Zhou, Yong-Gang Wei, Fei Liu, Ke-Fei Chen, Qiu Li, Bo Li
BACKGROUND: Transcatheter arterial chemoembolization (TACE) and TACE in combination with sorafenib (TACE-sorafenib) have shown a significant survival benefit for the treatment of unresectable hepatocellular carcinoma (HCC). Adopting either as a first-line therapy carries major cost and resource implications. The objective of this study was to estimate the relative cost-effectiveness of TACE against TACE-sorafenib for unresectable HCC using a decision analytic model. METHODS: A Markov cohort model was developed to compare TACE and TACE-sorafenib...
October 15, 2017: Hepatobiliary & Pancreatic Diseases International: HBPD INT
https://www.readbyqxmd.com/read/28992660/alpha-mangostin-inhibits-hepatic-stellate-cells-activation-through-tgf-%C3%AE-smad-and-akt-signaling-pathways-an-in-vitro-study-in-lx2
#20
Rahmaniah Rahmaniah, Yuyuntia Yuyuntia, Vivian Soetikno, Wawaimuli Arozal, Radiana Dhewayani Antarianto, Melva Louisa
Background Alpha mangostin has been reported to have activity for the treatment of liver fibrosis in the rats. However, the mechanisms of action are poorly understood. This study was aimed to investigate the effect of alpha mangostin on hepatic stellate cells (HSC) activation and proliferation through TGF-β/Smad and Akt signaling pathways. Methods Immortalized HSC, LX2 cells, were incubated with TGF-β with or without alpha mangostin (5 or 10 μM). Sorafenib 10 µM was used as positive control. LX2 viability was counted using trypan blue exclusion method...
October 9, 2017: Drug Research
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