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Sorafenib

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https://www.readbyqxmd.com/read/28548966/targeting-shp-1-stat3-signaling-a-promising-therapeutic-approach-for-the-treatment-of-cholangiocarcinoma
#1
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...
May 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28548943/intra-tumour-molecular-heterogeneity-of-clear-cell-renal-cell-carcinoma-reveals-the-diversity-of-the-response-to-targeted-therapies-using-patient-derived-xenograft-models
#2
Baoan Hong, Yong Yang, Sheng Guo, Shayiremu Duoerkun, Xiaohu Deng, Dawei Chen, Shijun Yu, Wubin Qian, Qixiang Li, Qing Li, Kan Gong, Ning Zhang
Inter- and intra-tumour molecular heterogeneity is increasingly recognized in clear cell renal cell carcinoma (ccRCC). It may partially explain the diversity of responses to targeted therapies and the various clinical outcomes. In this study, a 56-year-old male ccRCC patient with multiple metastases received radical nephrectomy and resection of the metastatic tumour in chest wall. The surgical specimens were implanted into nude mice to establish patient-derived xenograft (PDX) models with KI2367 model derived from the primary tumour and KI2368 model from the metastastic tumour...
May 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28548930/comparison-of-treatment-outcome-between-living-donor-liver-transplantation-and-sorafenib-for-patients-with-hepatocellular-carcinoma-beyond-the-milan-criteria
#3
Yuri Cho, Jeong-Hoon Lee, Dong Hyeon Lee, Eun Ju Cho, Su Jong Yu, Nam-Joon Yi, Kwang-Woong Lee, Yoon Jun Kim, Jung-Hwan Yoon, Kyung-Suk Suh
For patients with advanced hepatocellular carcinoma (HCC), sorafenib is the only systemic treatment recommended by international guidelines. We recently reported that HCC patients with a low MoRAL (model to predict tumor recurrence after LDLT) score (≤ 314.8) have excellent treatment outcomes after living-donor liver transplantation (LDLT), even though they are beyond the Milan criteria. In the present study, we investigated whether LDLT offers a better treatment outcome than sorafenib for patients with HCC beyond the Milan criteria according to the MoRAL score...
May 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28545562/the-inhibition-of-fgf-receptor-1-activity-mediates-sorafenib-antiproliferative-effects-in-human-malignant-pleural-mesothelioma-tumor-initiating-cells
#4
Alessandra Pattarozzi, Elisa Carra, Roberto E Favoni, Roberto Würth, Daniela Marubbi, Rosa Angela Filiberti, Luciano Mutti, Tullio Florio, Federica Barbieri, Antonio Daga
BACKGROUND: Malignant pleural mesothelioma is an aggressive cancer, characterized by rapid progression and high mortality. Persistence of tumor-initiating cells (TICs, or cancer stem cells) after cytotoxic drug treatment is responsible for tumor relapse, and represents one of the main reasons for the poor prognosis of mesothelioma. In fact, identification of the molecules affecting TIC viability is still a significant challenge. METHODS: TIC-enriched cultures were obtained from 10 human malignant pleural mesotheliomas and cultured in vitro...
May 25, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28545036/the-long-non-coding-rna-neat1-enhances-epithelial-to-mesenchymal-transition-and-chemoresistance-via-the-mir-34a-c-met-axis-in-renal-cell-carcinoma
#5
Fei Liu, Na Chen, Yanchun Gong, Ruihai Xiao, Weichao Wang, Zhengyue Pan
Long non-coding RNAs (lncRNAs) have emerged as new gene regulators and prognostic markers in various cancers. Although the lncRNA nuclear enriched abundant transcript 1 (NEAT1) has been associated with tumorigenesis, its functions in renal cell carcinoma (RCC) have not been elucidated. We determined that NEAT1 is up-regulated in RCC tissue compared to corresponding non-tumor tissue. High NEAT1 expression was associated with tumor progression and poor survival in RCC patients. NEAT1 knockdown suppressed RCC cell proliferation by inhibiting cell cycle progression, and inhibited RCC cell migration and invasion by reversing the epithelial-to- mesenchymal transition phenotype...
May 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28544385/korean-red-ginseng-extract-enhances-the-anticancer-effects-of-sorafenib-through-abrogation-of-creb-and-c-jun-activation-in-renal-cell-carcinoma
#6
Chulwon Kim, Jong Hyun Lee, Seung Ho Baek, Jeong-Hyeon Ko, Dongwoo Nam, Kwang Seok Ahn
Although application of sorafenib in the treatment of human renal cell carcinoma (RCC) remains one of the best examples of successful targeted therapy, majority of RCC patients suffer from its side effects as well as develop resistance to this targeted therapy. Thus, there is a need to promote novel alternative therapies for the treatment of RCC. In this study, we investigated whether Korean red ginseng extract (KRGE) could inhibit the proliferation and induce chemosensitization in human renal cancer cells...
May 22, 2017: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/28542880/suicidal-death-of-erythrocytes-in-cancer-and-its-chemotherapy-a-potential-target-in-the-treatment-of-tumor-associated-anemia
#7
REVIEW
Elisabeth Lang, Rosi Bissinger, Syed M Qadri, Florian Lang
In analogy to apoptosis of nucleated cells, erythrocytes may enter eryptosis characterized by cell shrinkage and cell membrane scrambling. Eryptotic erythrocytes are rapidly cleared from circulating blood and may adhere to the vascular wall. Stimulation of eryptosis thus impairs microcirculation and leads to anemia as soon as the loss of erythrocytes cannot be fully compensated by enhanced erythropoiesis. Signaling stimulating eryptosis includes increase of cytosolic Ca(2+) -activity, ceramide, caspases, calpain, p38-kinase, protein-kinase C, Janus-activated kinase 3, casein-kinase 1α, and cyclin-dependent kinase 4...
May 23, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28537899/nras-mutations-in-cutaneous-t-cell-lymphoma-ctcl-sensitize-tumors-towards-treatment-with-the-multikinase-inhibitor-sorafenib
#8
Michael K Kießling, Jan P Nicolay, Tabea Schlör, Claus-Detlev Klemke, Dorothee Süss, Peter H Krammer, Karsten Gülow
Therapy of cutaneous T cell lymphoma (CTCL) is complicated by a distinct resistance of the malignant T cells towards apoptosis that can be caused by NRAS mutations in late-stage patients. These mutations correlate with decreased overall survival, but sensitize the respective CTCL cells towards MEK-inhibition-induced apoptosis which represents a promising novel therapeutic target in CTCL. Here, we show that the multi-kinase inhibitor Sorafenib induces apoptosis in NRAS-mutated CTCL cells. CTCL cell lines and to a minor extent primary T cells from Sézary patients without NRAS mutations are also affected by Sorafenib-induced apoptosis suggesting a sensitizing role of NRAS mutations for Sorafenib-induced apoptosis...
May 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28536660/sorafenib-associated-heart-failure-complicated-by-cardiogenic-shock-after-treatment-of-advanced-stage-hepatocellular-carcinoma-a-clinical-case-discussion
#9
Candace Wu, Kamal Shemisa
Background. Sorafenib, an oral tyrosine kinase inhibitor (TKI), targets multiple tyrosine kinase receptors (TKRs) involved in angiogenesis and tumor growth. Studies suggest that inhibition of TKR impacts cardiomyocyte survival. Inhibition of VEGF signaling interrupts angiogenesis and is associated with the development of hypertension and compensatory hypertrophy. Compensated hypertrophy ultimately leads to heart failure. Case Description. A 76-year-old man with a past medical history of systolic heart failure due to ischemic cardiomyopathy and stage IIIC hepatocellular carcinoma (HCC) presented with symptoms of decompensated heart failure...
2017: Case Reports in Cardiology
https://www.readbyqxmd.com/read/28536078/akt-is-critically-involved-in-the-antagonism-of-braf-inhibitor-sorafenib-against-dabrafenib-in-colorectal-cancer-cells-harboring-both-wild-type-and-mutant-v600e-braf-genes
#10
Hongbin Wang, Haitian Quan, Liguang Lou
BRAF, one of the key factors in mitogen-activated protein kinase (MAPK) signaling pathway, plays an important role in cell functions including growth and proliferation. Inhibition of BRAF represents a promising antitumor strategy. Dabrafenib, a type I inhibitor of BRAF interrupting RAF/MEK interaction, has been approved by FDA as a single agent or combined with MEK inhibitor trametinib for the treatment of patients with BRAF V600E mutation-positive advanced melanoma. In the present study, we investigated the feasibility of combined treatment with dabrafenib and sorafenib, type I and type II BRAF inhibitor respectively, on colorectal cancer cells with BRAF V600E mutation...
May 20, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28531203/potential-health-gains-for-patients-with-metastatic-renal-cell-carcinoma-in-daily-clinical-practice-a-real-world-cost-effectiveness-analysis-of-sequential-first-and-second-line-treatments
#11
S De Groot, H M Blommestein, W K Redekop, S Sleijfer, L A L M Kiemeney, E Oosterwijk, C A Uyl-de Groot
INTRODUCTION: Randomised controlled trials have shown that targeted therapies like sunitinib are effective in metastatic renal cell carcinoma (mRCC). Little is known about the current use of these therapies, and their associated costs and effects in daily clinical practice. We estimated the real-world cost-effectiveness of different treatment strategies comprising one or more sequentially administered drugs. METHODS: Analyses were performed using patient-level data from a Dutch population-based registry including patients diagnosed with primary mRCC from January 2008 to December 2010 (i...
2017: PloS One
https://www.readbyqxmd.com/read/28529557/a-single-center-experience-of-sorafenib-monotherapy-in-patients-with-advanced-intrahepatic-cholangiocarcinoma
#12
Ting-Ting Pan, Wei Wang, Wei-Dong Jia, Ge-Liang Xu
Patients with advanced intrahepatic cholangiocarcinoma (ICC) have a poor prognosis and the therapeutic options available for treating ICC are limited. Sorafenib, a multikinase inhibitor of vascular endothelial growth factor receptor 2 and 3, platelet derived growth factor receptor-β, B-Raf proto-oncogene, serine/threonine kinase and C-Raf proto-oncogene, serine/threonine kinase, is a novel reference standard for the treatment of advanced hepatocellular carcinoma. Sorafenib has previously been demonstrated to exhibit significant antitumor activity in various cholangiocarcinoma cell lines and in xenograft ICC models...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28524813/a-multifunctional-nanocomplex-for-enhanced-cell-uptake-endosomal-escape-and-improved-cancer-therapeutic-effect
#13
Patrick V Almeida, Mohammad-Ali Shahbazi, Alexandra Correia, Ermei Mäkilä, Marianna Kemell, Jarno Salonen, Jouni Hirvonen, Hélder A Santos
AIM: To evaluate the chemotherapeutic potential of a novel multifunctional nanocomposite encapsulating both porous silicon (PSi) and gold (Au) nanoparticles in a polymeric nanocomplex. MATERIALS & METHODS: The nanocomposite was physicochemically characterized and evaluated in vitro for biocompatibility, cellular internalization, endosomolytic properties, cytoplasmatic drug delivery and chemotherapeutic efficacy. RESULTS: The nanocomposites were successfully produced and exhibited adequate physicochemical properties and superior in vitro cyto- and hemocompatibilities...
May 19, 2017: Nanomedicine
https://www.readbyqxmd.com/read/28522682/regorafenib-approved-for-liver-cancer
#14
(no author information available yet)
The FDA recently expanded label indications for regorafenib to include treating patients with advanced hepatocellular carcinoma whose disease has progressed on the standard of care, sorafenib. Until now, these patients have had no other treatment options. Regorafenib is the first drug to be approved for liver cancer in a decade.
May 18, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28521783/association-of-post-treatment-hypoalbuminemia-and-survival-in-chinese-patients-with-metastatic-renal-cell-carcinoma
#15
Wen Cai, Jin Zhang, Yonghui Chen, Wen Kong, Yiran Huang, Jiwei Huang, Lixin Zhou
BACKGROUND: Hypoalbuminemia adversely affects the clinical outcomes of various cancers. The purpose of this study was to estimate the prognostic value of hypoalbuminemia 3-5 weeks after treatment in patients with metastatic renal cell carcinoma (mRCC) who received sorafenib or sunitinib as first-line treatment. METHODS: In this single-center, retrospective study, we assessed the progression-free survival (PFS) and overall survival (OS) of 184 mRCC patients who received first-line sorafenib or sunitinib treatment...
May 18, 2017: Chinese Journal of Cancer
https://www.readbyqxmd.com/read/28521494/sub-classification-of-advance-stage-hepatocellular-carcinoma-a-cohort-study-including-612-patients-treated-with-sorafenib
#16
Jeong-Ju Yoo, Goh Eun Chung, Jeong-Hoon Lee, Joon Yeul Nam, Young Chang, Jeong Min Lee, Dong Ho Lee, Hwi Young Kim, Eun Ju Cho, Su Jong Yu, Yoon Jun Kim, Jung-Hwan Yoon
Purpose: Advanced hepatocellular carcinoma (HCC) is associated with various clinical conditions including major vessel invasion, metastasis, and poor performance status. The aim of this study was to establish a prognostic scoring system and to propose a sub-classification of the Barcelona-Clinic Liver Cancer (BCLC) stage C. Materials and Methods: This retrospective study included consecutive patients who received sorafenib for BCLC stage C HCC at a single tertiary hospital in Korea...
May 15, 2017: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/28515920/predictive-value-of-the-modified-glasgow-prognostic-score-for-the-therapeutic-effects-of-molecular-targeted-drugs-on-advanced-renal-cell-carcinoma
#17
Hirofumi Ohmura, Keita Uchino, Tatsuhiro Kajitani, Naotaka Sakamoto, Eishi Baba
Inflammation is considered to be a prognostic factor for renal cell carcinoma (RCC). An inflammation-based prognostic score (modified Glasgow Prognostic Score; mGPS) is widely used for preoperative patients; however, little information is available regarding its prognostic value in patients with RCC treated with molecular-targeted drugs. A total of 32 advanced and recurrent RCC patients initially treated with molecular-targeted drugs from October, 2009 to August, 2015 were retrospectively investigated. Information on patient characteristics prior to treatment initiation and the clinical course were retrieved from clinical records...
May 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28515157/carboxyamidotriazole-synergizes-with-sorafenib-to-combat-non-small-cell-lung-cancer-through-inhibition-of-nanog-and-aggravation-of-apoptosis
#18
Chen Chen, Rui Ju, Jing Shi, Wei Chen, Fangrui Sun, Lei Zhu, Juan Li, Dechang Zhang, Caiying Ye, Lei Guo
Lung cancer is the leading cause of cancer-related deaths in the world. In this study, we investigated the combination of carboxyamidotriazole (CAI) and sorafenib in NSCLC in vitro and in vivo, to test whether CAI enhances the antitumor effects of sorafenib and reduces its side effects. The combination index (CI) showed that co-administration of CAI and sorafenib synergistically inhibited the proliferation of NSCLC cells (Lewis lung carcinoma, A549, NCI-H1975). The cell death led by the treatment of combination drugs was attributed to apoptosis which was accompanied with activation of caspase 3 and poly ADP-ribose polymerase...
May 17, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28512387/oncolytic-virus-based-immunotherapies-for-hepatocellular-carcinoma
#19
REVIEW
So Young Yoo, Narayanasamy Badrinath, Hyun Young Woo, Jeong Heo
Hepatocellular carcinoma is highly refractory cancer which is resistant to conventional chemotherapy and radiotherapy, carrying a dismal prognosis. Although many anticancer drugs have been developed for treating HCC, sorafenib is the only effective treatment, but it only prolongs survival duration for about 3 months. Recently, oncolytic virotherapy has shown promising results in treating HCCs and the effects can be more enhanced by adopting immune modulatory molecules. This review discusses the current status of treating HCC and the effective strategy of oncolytic virus-based immunotherapy for the treatment of HCCs...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28509806/advances-in-management-of-hepatocellular-carcinoma
#20
Manon Allaire, Jean-Charles Nault
PURPOSE OF REVIEW: Hepatocellular carcinoma (HCC) is one of the leading causes of death by cancer worldwide due to a dismal prognosis. The aim of this review is to summarize the main advances in the pathophysiology and management of HCC. RECENT FINDINGS: Genomic analysis has recently delineated the key signaling pathways aberrantly deregulated in HCC (telomere maintenance, cell cycle gene, Wnt/β-catenin, epigenetic modifier, oxidative stress etc.). Major advances in the clinical care of patients with HCC are helping to refine the diagnosis algorithm and tumor staging...
May 15, 2017: Current Opinion in Oncology
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