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https://www.readbyqxmd.com/read/28212559/the-selective-mek1-inhibitor-selumetinib-enhances-the-antitumor-activity-of-everolimus-against-renal-cell-carcinoma-in-vitro-and-in-vivo
#1
Yun Zou, Jianfeng Wang, Xuejiao Leng, Jiwei Huang, Wei Xue, Jin Zhang, Yiran Huang
Renal cell carcinoma (RCC) is a urologic malignant cancer and often diagnosed at an advanced stage, which results in high mortality. Targeted therapy may improve the quality of life and survival of patients who are not suitable for nephrectomy. Everolimus, an mTOR inhibitor, is currently used as sequential or second-line therapy for RCC refractory to Sunitinib or sorafenib. However, its efficiency is palliative. In this study, we evaluated whether the antitumor activity of everolimus against RCC is enhanced by Selumetinib, a selective MEK1 inhibitor...
February 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28212535/integration-of-the-cancer-related-inflammatory-response-as-a-stratifying-biomarker-of-survival-in-hepatocellular-carcinoma-treated-with-sorafenib
#2
Jessica Howell, David J Pinato, Ramya Ramaswami, Tadaaki Arizumi, Carlotta Ferrari, Antonello Gibbin, Michela E Burlone, Giulia Guaschino, Pierluigi Toniutto, James Black, Laura Sellers, Masatoshi Kudo, Mario Pirisi, Rohini Sharma
BACKGROUND AND AIMS: Response to sorafenib is highly variable in hepatocellular carcinoma (HCC). Baseline inflammatory parameters and treatment toxicities may improve survival prediction in patients on sorafenib therapy. RESULTS: 442 patients with advanced stage HCC on sorafenib were recruited (follow-up 5096 person-months at risk). 88% had BCLC stage B or greater HCC and 72.3% had Child-Pugh A cirrhosis. On Cox multivariate regression, previously-treated HCC (HR 0...
February 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28211921/metronomic-capecitabine-versus-best-supportive-care-as-second-line-treatment-in-hepatocellular-carcinoma-a-retrospective-study
#3
Andrea Casadei Gardini, Flavia Foca, Mario Scartozzi, Nicola Silvestris, Emiliano Tamburini, Luca Faloppi, Oronzo Brunetti, Britt Rudnas, Salvatore Pisconti, Martina Valgiusti, Giorgia Marisi, Francesco Giuseppe Foschi, Giorgio Ercolani, Davide Tassinari, Stefano Cascinu, Giovanni Luca Frassineti
Preliminary studies suggest that capecitabine may be safe and effective in HCC patients. The aim of this study was to retrospectively evaluate the safety and efficacy of metronomic capecitabine as second-line treatment. This multicentric study retrospectively analyzed data of HCC patients unresponsive or intolerant to sorafenib treatment with metronomic capecitabine or best supportive care (BSC).Median progression free survival was 3.1 months in patients treated with capecitabine (95%CI: 2.7-3.5). Median overall survival was 12...
February 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28205224/muc13-overexpression-in-renal-cell-carcinoma-plays-a-central-role-in-tumour-progression-and-drug-resistance
#4
Yonghua Sheng, Choa Ping Ng, Rohan Lourie, Esha T Shah, Yaowu He, Kuan Yau Wong, Inge Seim, Iulia Oancea, Christudas Morais, Penny L Jeffery, John Hooper, Glenda C Gobe, Michael A McGuckin
Metastatic renal cell carcinoma is a largely incurable disease, and existing treatments targeting angiogenesis and tyrosine kinase receptors are only partially effective. Here we reveal that MUC13, a cell surface mucin glycoprotein, is aberrantly expressed by most renal cell carcinomas, with increasing expression positively correlating with tumor grade. Importantly, we demonstrated that high MUC13 expression was a statistically significant independent predictor of poor survival in two independent cohorts, particularly in stage 1 cancers...
February 16, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28203091/expression-of-microrna-30c-via-lentivirus-vector-inhibits-the-proliferation-and-enhances-the-sensitivity-of-highly-aggressive-ccrcc-caki-1-cells-to-anticancer-agents
#5
Honglin Yang, Erlin Song, Guorong Shen, Tonghua Zhu, Tingwang Jiang, Hao Shen, Liping Niu, Biao Wang, Zhaoyang Lu, Jianping Qian
The clear cell renal cell carcinoma (ccRCC) is one of the most fatal urologic tumors, and the prognosis remains very poor for advanced or metastatic ccRCC. This study reveals the roles of microRNA (miR)-30c in regulating a highly aggressive ccRCC cell line proliferation by targeting MTA-1, which is a key mediator for human cancer metastasis. Results from quantitative real-time polymerase chain reaction showed that the expression of MTA-1, the target of miR-30c, was significantly higher in metastatic ccRCC specimens than in nonmetastatic ccRCC or nontumor specimens...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28202430/vespro-an-individual-patient-data-prospective-meta-analysis-of-selective-internal-radiation-therapy-versus-sorafenib-for-advanced-locally-advanced-or-recurrent-hepatocellular-carcinoma-of-the-sarah-and-sirvenib-trials
#6
Val Gebski, Emma Gibbs, Mihir Gandhi, Gilles Chatellier, Aurelia Dinut, Helena Pereira, Pierce Kh Chow, Valérie Vilgrain
BACKGROUND: Untreated advanced hepatocellular carcinoma (HCC) has an overall poor prognosis. Currently there are 2 ongoing prospective randomized controlled trials that are evaluating the efficacy and safety of sorafenib and selective internal radiation therapy (SIRT) with yttrium-90 resin microspheres in patients with advanced HCC. The SorAfenib versus Radioembolisation in Advanced Hepatocellular carcinoma (SARAH; 459 patients) trial is being performed in Europe and the SIRt VErsus SorafeNIB (SIRveNIB; 360 patients) trial in the Asia Pacific region...
February 15, 2017: JMIR Research Protocols
https://www.readbyqxmd.com/read/28202227/phase-i-trial-of-radiation-therapy-and-sorafenib-in-unresectable-liver-metastases
#7
Rebecca B Goody, Anthony M Brade, Lisa Wang, Tim Craig, James Brierley, Robert Dinniwell, Rebecca K S Wong, Charles Cho, John Kim, Zahra Kassam, Jolie Ringash, Jennifer J Knox, Laura A Dawson
BACKGROUND AND PURPOSE: To determine maximum tolerated dose (MTD) and toxicities of sorafenib combined with stereotactic radiotherapy (SBRT) or whole liver radiotherapy (WLRT) in patients with liver metastases. MATERIAL AND METHODS: Eligible patients had unresectable liver metastases. Sorafenib dose was escalated in 2 strata: I - SBRT: effective liver volume irradiated (Veff)<80% (30-60Gy in 6 fractions); II - WLRT: Veff>80% (21.6Gy in 6 fractions). Four weeks of sorafenib, with radiotherapy during weeks 2-3, was delivered at 3 escalating dose levels (200-400mg twice daily)...
February 12, 2017: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
https://www.readbyqxmd.com/read/28198177/innovative-molecular-targeted-agents-in-hepatocellular-carcinoma-new-gladiators-on-the-arena
#8
Jose Ferri, Yanina Dockx, Luisa Vonghia, Konstantinos Papadimitriou, Marika Rasschaert, Sven Francque, Marc Peeters, Christian Rolfo
Treatment of advanced hepatocellular carcinoma remains a challenge, with discouraging results in terms of survival. Following the approval of the multikinase inhibitor sorafenib, a large number of molecular targeted agents have been tested, but many have failed to demonstrate significant efficacy in clinical trials. However, the deeper knowledge in HCC pathogenesis achieved through the years has enabled us to explore new targetable pathways as well as biomarkers that could lead to treatment personalization...
February 14, 2017: Minerva Chirurgica
https://www.readbyqxmd.com/read/28194038/itd-mutation-in-flt3-tyrosine-kinase-promotes-warburg-effect-and-renders-therapeutic-sensitivity-to-glycolytic-inhibition
#9
H-Q Ju, G Zhan, A Huang, Y Sun, S Wen, J Yang, W-H Lu, R-H Xu, J Li, Y Li, G Garcia-Manero, P Huang, Y Hu
Internal tandem duplication (ITD) mutation in Fms-like tyrosine kinase 3 gene (FLT3/ITD) represents an unfavorable genetic change in acute myeloid leukemia (AML) and is associated with poor prognosis. Metabolic alterations have been involved in tumor progression and attracted interest as a target for therapeutic intervention. However, few studies analyzed the adaptations of cellular metabolism in the context of FLT3/ITD mutation. Here, we report that FLT3/ITD causes a significant increase in aerobic glycolysis through AKT-mediated upregulation of mitochondrial hexokinase (HK2), and renders the leukemia cells highly dependent on glycolysis and sensitive to pharmacological inhibition of glycolytic activity...
February 14, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28193171/exceptional-serological-and-radiological-response-to-sorafenib-in-2-patients-with-advanced-hepatocellular-carcinoma-and-chronic-hepatitis-c-viral-infection-case-report-and-review-of-the-literature
#10
Catherine Atkin, Philip Earwaker, Arvind Pallan, Shishir Shetty, Pankaj Punia, Yuk Ting Ma
BACKGROUND: In patients with advanced hepatocellular carcinoma (HCC), the multikinase inhibitor sorafenib is the only systemic treatment that has been shown to increase overall survival. However, similar to other tyrosine kinase inhibitors, most patients achieve disease stabilisation radiologically, and only 2-3% of patients achieve a partial response. Recent exploratory subgroup analyses of the large phase 3 trials have demonstrated that patients with chronic hepatitis C virus (HCV) infection associated HCC survive longer than those who are negative for HCV...
February 14, 2017: BMC Gastroenterology
https://www.readbyqxmd.com/read/28186991/c-terminal-truncated-hepatitis-b-virus-x-protein-regulates-tumorigenicity-self-renewal-and-drug-resistance-via-stat3-nanog-signaling-pathway
#11
Rachel Hiu Ha Ching, Karen Man Fong Sze, Eunice Yuen Ting Lau, Yung-Tuen Chiu, Joyce Man Fong Lee, Irene Oi Lin Ng, Terence Kin Wah Lee
Hepatitis B virus (HBV) is a major risk factor of chronic liver disease and hepatocellular carcinoma (HCC). Random integration of HBV DNA into the host genome is frequent in HCC leading to truncation of the HBV DNA, particularly at the C-terminal end of the HBV X protein (HBx). C-terminally truncated HBx (HBx-ΔC) has been implicated in playing a pro-oncogenic role in hepatocarcinogenesis. However, the mechanism whereby HBx-ΔC1 contributes to hepatocarcinogenesis remains unclear. In this study, we investigated the functional role of HBx-ΔC1 in regulating liver cancer stem cell (CSC) properties...
February 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28179348/surgical-resection-for-lymph-node-metastasis-after-liver-transplantation-for-hepatocellular-carcinoma
#12
Toru Ikegami, Tomoharu Yoshizumi, Jyunji Kawasaki, Akihisa Nagatsu, Hideaki Uchiyama, Noboru Harada, Norifumi Harimoto, Shinji Itoh, Takashi Motomura, Yuji Soejima, Yoshihiko Maehara
BACKGROUND: Treatment strategies for lymph node (LN) metastasis after liver transplantation (LT) for hepatocellular carcinoma (HCC) have not been studied. PATIENTS AND METHODS: The treatment modes and outcomes in patients with LN metastasis after LT (n=6) for HCC were reviewed. RESULTS: The mean time from LT to LN recurrence was 2.0±1.3 years, and the locations of the LNs recurrences included the phrenic (n=2), common hepatic artery (n=2), inferior vena cava (n=1) and gastric (n=1) regions...
2017: Anticancer Research
https://www.readbyqxmd.com/read/28179093/sorafenib-and-fh535-in-combination-act-synergistically-on-hepatocellular-carcinoma-by-targeting-cell-bioenergetics-and-mitochondrial-function
#13
Lilia Turcios, Valery Vilchez, Luis F Acosta, Pratheeshkumar Poyil, David Allan Butterfield, Mihail Mitov, Francesc Marti, Roberto Gedaly
Treatment of advanced hepatocellular carcinoma (HCC) remains a challenge due to the high tumor heterogeneity. In the present study, we aim to evaluate the impact of the β-catenin inhibitor, FH535, alone or in combination with the Ras/Raf/MAPK inhibitor Sorafenib, on the bioenergetics profiles of the HCC cell lines Huh7 and PLC/PRF/5. Single low-dose treatments with FH535 or Sorafenib promoted different effects on mitochondrial respiration and glycolysis in a cell type specific manner. However, the combination of these drugs significantly reduced both mitochondrial respiration and glycolytic rates regardless of the HCC cells...
January 19, 2017: Digestive and Liver Disease
https://www.readbyqxmd.com/read/28178663/the-lack-of-the-organic-cation-transporter-oct1-at-the-plasma-membrane-of-tumor-cells-precludes-a-positive-response-to-sorafenib-in-patients-with-hepatocellular-carcinoma
#14
Andreas Geier, Rocio I R Macias, Dominik Bettinger, Johannes Weiss, Heike Bantel, Daniel Jahn, Ruba Al-Abdulla, Jose J G Marin
BACKGROUND: Sorafenib is the drug of choice in the treatment of advanced hepatocellular carcinoma (HCC). Beneficial effects are limited by mechanisms of chemoresistance, which include downregulation and/or impaired function of plasma membrane transporters accounting for drug uptake. The organic cation transporter 1 (OCT1) plays a major role in sorafenib uptake and decreased expression in HCC has been associated with poorer response. METHODS: The multicenter retrospective TRANSFER study involved tumor biopsies from 39 patients with advanced HCC and sorafenib therapy for ≥4 wk...
February 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28178378/melatonin-promotes-sorafenib-induced-apoptosis-through-synergistic-activation-of-jnk-c-jun-pathway-in-human-hepatocellular-carcinoma
#15
Shibo Lin, Katrin Hoffmann, Chao Gao, Marius Petrulionis, Ingrid Herr, Peter Schemmer
Melatonin has been shown to exert anticancer activity on hepatocellular carcinoma (HCC) through its anti-proliferative and pro-apoptotic effect in both experimental and clinical studies, and sorafenib is the only approved drug for the systemic treatment of HCC. Thus, this study was designed to investigate the combined effect of melatonin and sorafenib on proliferation, apoptosis and its possible mechanism in human HCC. Here, we found that both melatonin and sorafenib resulted in a dose-dependent growth inhibition of HuH-7 cells after 48 hours treatment, and the combination of them enhanced the growth inhibition in a synergistic manner...
February 8, 2017: Journal of Pineal Research
https://www.readbyqxmd.com/read/28177886/transarterial-chemoembolization-tace-combined-with-sorafenib-versus-tace-for-hepatocellular-carcinoma-with-portal-vein-tumor-thrombus-a-systematic-review-and-meta-analysis
#16
XiuPing Zhang, Kang Wang, Meng Wang, Guang Yang, XiaoFei Ye, MengChao Wu, ShuQun Cheng
BACKGROUND: The benefits of transarterial chemoembolization plus sorafenib (TACE-S) in hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) remain controversial. We compared the effectiveness and safety of TACE-S and TACE for HCC with PVTT. METHODS: The Cochrane Library, PubMed, EMBASE, Chinese National Knowledge Infrastructure, VIP, Wan Fang, and Sino Med databases were systematically searched for studies of HCC with PVTT treated using TACE-S. Two authors independently extracted study outcomes, including overall survival (OS), time to progression (TTP), objective response (tumor response) and adverse events (AEs)...
February 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28174660/mrgfus-for-desmoid-tumors-within-the-thigh-early-clinical-experiences
#17
Matthew D Bucknor, Viola Rieke
BACKGROUND: Desmoid tumors are benign but locally aggressive non-malignant tumors derived from fibroblasts. Surgery, chemotherapy, and radiation therapy have been the mainstay of treatment, but recurrence is common and side effects can result in significant morbidity. In this case series, we highlight our experiences performing treatments in the thigh, including strategies for optimizing ablation size and safety. CASE PRESENTATION: Since December 2014, 14 magnetic resonance-guided focused ultrasound (MRgFUS) treatments for desmoid tumors were performed at our institution in seven patients...
2017: Journal of Therapeutic Ultrasound
https://www.readbyqxmd.com/read/28174094/recent-advances-in-hepatocellular-carcinoma-therapy
#18
REVIEW
Rinku Dutta, Ram I Mahato
Hepatocellular carcinoma (HCC), also called malignant hepatoma, is one of the deadliest cancers due to its complexities, reoccurrence after surgical resection, metastasis and heterogeneity. Incidence and mortality of HCC are increasing in Western countries and are expected to rise as a consequence of the obesity epidemic. Multiple factors trigger the initiation and progression of HCC including chronic alcohol consumption, viral hepatitis B and C infection, metabolic disorders and age. Although Sorafenib is the only FDA approved drug for the treatment of HCC, numerous treatment modalities such as transcatheter arterial chemoembolization/ transarterial chemoembolization (TACE), radiotherapy, locoregional therapy and chemotherapy have been tested in the clinics...
February 4, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28167571/pharmacoepidemiology-of-clinically-relevant-hypothyroidism-and-hypertension-from-sunitinib-and-sorafenib
#19
Christine M Walko, Ronald E Aubert, Ninh M La-Beck, Gosia Clore, Vivian Herrera, Helen Kourlas, Robert S Epstein, Howard L McLeod
BACKGROUND: Thyroid dysfunction and hypertension (HTN) have been sporadically reported with sunitinib (SUN) and sorafenib (SOR). Determination of the side effect incidence will enhance monitoring and management recommendations. METHODS: An observational cohort study was performed using deidentified pharmacy claims data from a 3-year period to evaluate patients prescribed SUN, SOR, or capecitabine (CAP; comparison group). The primary outcome was time to first prescription for thyroid replacement or HTN treatment...
February 6, 2017: Oncologist
https://www.readbyqxmd.com/read/28165798/improving-anti-tumor-activity-of-sorafenib-tosylate-by-lipid-and-polymer-coated-nanomatrix
#20
Yang Guo, Ting Zhong, Xiao-Chuan Duan, Shuang Zhang, Xin Yao, Yi-Fan Yin, Dan Huang, Wei Ren, Qiang Zhang, Xuan Zhang
In the present study, we select the Sylysia 350 (Sylysia) as mesoporous material, distearoylphosphatidylethanolamine-poly(ethylene glycol)2000 (DSPE-PEG) as absorption enhancer and hydroxy propyl methyl cellulose (HPMC) as crystallization inhibitor to prepare sorafenib tosylate (SFN) nanomitrix (MSNM@SFN) for improving the anti-tumor activity of SFN. The MSNM@SFN was prepared by solvent evaporation method. The solubility, dissolution, and bioavailability of SFN in MSNM@SFN were also investigated. The anti-tumor activity of MSNM@SFN was evaluated in vitro and in vivo...
November 2017: Drug Delivery
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