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Sorafenib

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https://www.readbyqxmd.com/read/28454454/chemotherapy-regimen-based-on-sorafenib-combined-with-5-fu-on-hif-1%C3%AE-and-vegf-expression-and-survival-in-advanced-gastric-cancer-patients
#1
Ronghui Cheng, Hongmei Yong, Yunhong Xia, Qingsong Xie, Guangyi Gao, Xueyi Zhou
The present study investigated the effect of combined sorafenib chemotherapy on hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) expression and survival time of patients with advanced gastric cancer. From January 2010 to December 2011, 92 patients diagnosed with advanced gastric cancer were selected and randomly divided into the treatment group and control group. The treatment group was treated with sorafenib chemotherapy combined with 5-fluorouracil (5-FU), and the control group received 5-FU...
April 2017: Oncology Letters
https://www.readbyqxmd.com/read/28454244/proliferation-of-sphere-forming-hepatocellular-carcinoma-cells-is-suppressed-in-a-medium-without-glucose-and-arginine-but-with-galactose-and-ornithine
#2
Minoru Tomizawa, Fuminobu Shinozaki, Yasufumi Motoyoshi, Takao Sugiyama, Shigenori Yamamoto, Naoki Ishige
Resistance to sorafenib in hepatocellular carcinoma (HCC) cells exhibiting stemness was evaluated using a sphere formation assay. A hepatocyte selection medium (HSM) deficient in glucose and arginine was used to suppress the proliferation of cell spheres composed of HLF and PLC/PRF/5 HCC cells, which were subjected to a sphere formation assay. Cell spheres were cultured with sorafenib and subjected to a cell proliferation assay and the expression levels of cytochrome P450 (CYP3A4) were analyzed in RNA extracted from sphere-forming cells using reverse transcription-quantitative polymerase chain reaction...
March 2017: Oncology Letters
https://www.readbyqxmd.com/read/28448047/a-syngeneic-mouse-model-of-metastatic-renal-cell-carcinoma-for-quantitative-and-longitudinal-assessment-of-preclinical-therapies
#3
Katherine A Murphy, Britnie R James, Andrew Wilber, Thomas S Griffith
Renal cell carcinoma (RCC) affects > 60,000 people in the United States annually, and ~ 30% of RCC patients have multiple metastases at the time of diagnosis. Metastatic RCC (mRCC) is incurable, with a median survival time of only 18 months. Immune-based interventions (e.g., interferon (IFN) and interleukin (IL)-2) induce durable responses in a fraction of mRCC patients, and multikinase inhibitors (e.g., sunitinib or sorafenib) or anti-VEGF receptor monoclonal antibodies (mAb) are largely palliative, as complete remissions are rare...
April 12, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28447912/targeting-ret-in-patients-with-ret-rearranged-lung-cancers-results-from-the-global-multicenter-ret-registry
#4
Oliver Gautschi, Julie Milia, Thomas Filleron, Juergen Wolf, David P Carbone, Dwight Owen, Ross Camidge, Vignhesh Narayanan, Robert C Doebele, Benjamin Besse, Jordi Remon-Masip, Pasi A Janne, Mark M Awad, Nir Peled, Chul-Cho Byoung, Daniel D Karp, Michael Van Den Heuvel, Heather A Wakelee, Joel W Neal, Tony S K Mok, James C H Yang, Sai-Hong Ignatius Ou, Georg Pall, Patrizia Froesch, Gérard Zalcman, David R Gandara, Jonathan W Riess, Vamsidhar Velcheti, Kristin Zeidler, Joachim Diebold, Martin Früh, Sebastian Michels, Isabelle Monnet, Sanjay Popat, Rafael Rosell, Niki Karachaliou, Sacha I Rothschild, Jin-Yuan Shih, Arne Warth, Thomas Muley, Florian Cabillic, Julien Mazières, Alexander Drilon
Purpose In addition to prospective trials for non-small-cell lung cancers (NSCLCs) that are driven by less common genomic alterations, registries provide complementary information on patient response to targeted therapies. Here, we present the results of an international registry of patients with RET-rearranged NSCLCs, providing the largest data set, to our knowledge, on outcomes of RET-directed therapy thus far. Methods A global, multicenter network of thoracic oncologists identified patients with pathologically confirmed NSCLC that harbored a RET rearrangement...
May 1, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28445298/barcelona-clinic-liver-cancer-stage-c-hepatocellular-carcinoma-a-novel-approach-to-subclassification-and-treatment
#5
Chung Hwan Jun, Jae Hyun Yoon, Eunae Cho, Sang Soo Shin, Sung Bum Cho, Hee Joon Kim, Chang Hwan Park, Hyun Soon Kim, Sung Kyu Choi, Jong Sun Rew
Barcelona clinic liver cancer-stage C (BCLC-C) encompasses a broad spectrum of tumor burdens, liver function statuses, patient prognoses, and treatment strategies. Currently, sorafenib is the only recommended treatment for patients with BCLC-C and outcomes remain suboptimal. The aims of this study were to assess the heterogeneity of BCLC-C hepatocellular carcinoma (HCC) cases, propose a novel subclassification for these cases, and suggest optimal treatment strategies other than sorafenib.We retrospectively analyzed 196 consecutive BCLC-C HCC patients who were diagnosed and treated between January 2008 and December 2015...
April 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28440736/levistilide-a-inhibits-angiogenesis-in-liver-fibrosis-via-vascular-endothelial-growth-factor-signaling-pathway
#6
Zhi-Min Zhao, Hong-Liang Liu, Xin Sun, Tao Guo, Li Shen, Yan-Yan Tao, Cheng-Hai Liu
Levistilide A (C24H28O4, molecular weight = 380.48) derived from Angelica sinensis (Danggui) has been reported to inhibit hepatic stellate cell proliferation. This study investigated the effects of levistilide A on liver fibrosis relating to angiogenesis, particularly on the characteristic change in liver sinusoidal endothelial cells. LX-2 cells were activated by TGF-β1, and the human hepatic sinusoidal endothelial cells (HHSECs) were induced by endothelial cell growth supplement. Cell viability was detected using a methylthiazoldiphenyl-tetrazolium bromide assay; F-actin was visualized through the fluorescence probe method; cell proliferation was examined using the EdU kit; antiangiogenesis activity was assessed using the tube formation assay and transgenic zebrafish model...
May 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28439950/protein-disulfide-isomerase-inhibition-synergistically-enhances-the-efficacy-of-sorafenib-for-hepatocellular-carcinoma
#7
Jae-Kyung Won, Su Jong Yu, Chae Young Hwang, Sung-Hwan Cho, Sang-Min Park, Kwangsoo Kim, Won-Mook Choi, Hyeki Cho, Eun Ju Cho, Jeong-Hoon Lee, Kyung Bun Lee, Yoon Jun Kim, Kyung-Suk Suh, Ja-June Jang, Chung Yong Kim, Jung-Hwan Yoon, Kwang-Hyun Cho
Sorafenib is the only approved targeted drug for hepatocellular carcinoma (HCC), but its effect on patients' survival gain is limited and varies over a wide range depending on patho-genetic conditions. Thus, enhancing the efficacy of sorafenib and finding a reliable predictive biomarker are crucial to achieve efficient control of HCCs. In this study, we employed a systems approach by combining transcriptome analysis of the mRNA changes in HCC cell lines in response to sorafenib with network analysis to investigate the action and resistance mechanism of sorafenib...
April 25, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28439491/translating-new-data-to-the-daily-practice-in-second-line-treatment-of-renal-cell-carcinoma-the-role-of-tumor-growth-rate
#8
EDITORIAL
Enrique Grande, Olga Martínez-Sáez, Pablo Gajate-Borau, Teresa Alonso-Gordoa
The therapeutic options for patients with metastatic renal cell carcinoma (mRCC) have completely changed during the last ten years. With the sequential use of targeted therapies, median overall survival has increased in daily practice and now it is not uncommon to see patients surviving kidney cancer for more than four to five years. Once treatment fails with the first line targeted therapy, head to head comparisons have shown that cabozantinib, nivolumab and the combination of lenvatinib plus everolimus are more effective than everolimus alone and that axitinib is more active than sorafenib...
April 10, 2017: World Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28434648/nivolumab-in-patients-with-advanced-hepatocellular-carcinoma-checkmate-040-an-open-label-non-comparative-phase-1-2-dose-escalation-and-expansion-trial
#9
Anthony B El-Khoueiry, Bruno Sangro, Thomas Yau, Todd S Crocenzi, Masatoshi Kudo, Chiun Hsu, Tae-You Kim, Su-Pin Choo, Jörg Trojan, Theodore H Welling, Tim Meyer, Yoon-Koo Kang, Winnie Yeo, Akhil Chopra, Jeffrey Anderson, Christine Dela Cruz, Lixin Lang, Jaclyn Neely, Hao Tang, Homa B Dastani, Ignacio Melero
BACKGROUND: For patients with advanced hepatocellular carcinoma, sorafenib is the only approved drug worldwide, and outcomes remain poor. We aimed to assess the safety and efficacy of nivolumab, a programmed cell death protein-1 (PD-1) immune checkpoint inhibitor, in patients with advanced hepatocellular carcinoma with or without chronic viral hepatitis. METHODS: We did a phase 1/2, open-label, non-comparative, dose escalation and expansion trial (CheckMate 040) of nivolumab in adults (≥18 years) with histologically confirmed advanced hepatocellular carcinoma with or without hepatitis C or B (HCV or HBV) infection...
April 20, 2017: Lancet
https://www.readbyqxmd.com/read/28430610/treatment-of-hepatocellular-carcinoma-with-portal-vein-tumor-thrombus-advances-and-challenges
#10
REVIEW
Jin-Fang Jiang, Yong-Cong Lao, Bao-Hong Yuan, Jun Yin, Xin Liu, Long Chen, Jian-Hong Zhong
Portal vein tumor thrombus is a frequent, challenging complication in hepatocellular carcinoma. Hepatocellular carcinoma patients with portal vein tumor thrombus may show worse liver function, less treatment tolerance and worse prognosis than patients without portal vein tumor thrombus, and they may be at higher risk of comorbidity related to portal hypertension. Western and some Asian guidelines stratify hepatocellular carcinoma with portal vein tumor thrombus together with metastatic hepatocellular carcinoma and therefore recommend only palliative treatment with sorafenib or other systemic agents...
February 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28426123/cabozantinib-in-hepatocellular-carcinoma-results-of-a-phase-2-placebo-controlled-randomized-discontinuation-study
#11
R K Kelley, C Verslype, A L Cohn, T-S Yang, W-C Su, H Burris, F Braiteh, N Vogelzang, A Spira, P Foster, Y Lee, E Van Cutsem
Background: Cabozantinib, an orally bioavailable inhibitor of tyrosine kinases including MET, AXL, and VEGF receptors, was assessed in patients with hepatocellular carcinoma (HCC) as part of a phase 2 randomized discontinuation trial with nine tumor-type cohorts. Patients and methods: Eligible patients had Child-Pugh A liver function and ≤1 prior systemic anticancer regimen, completed ≥4 weeks before study entry. The cabozantinib starting dose was 100 mg daily...
March 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28424553/the-world-of-targeted-therapies-in-kidney-cancers-pitfalls-tips-and-tricks
#12
Alexis Vallard, Jane-Chloé Trone, Julien Langrand-Escure, Sophie Espenel, Jean-Baptiste Guy, Chloé Rancoule, Yaoxiong Xia, Anis El Meddeb Hamrouni, Majed Ben Mrad, Nicolas Magné
In the past few years, metastatic renal cell carcinoma prognosis was improved by the development of molecular targeted therapies (TTs). At the metastatic stage, the tolerance to treatment is a major concern, not only because of the challenge of the efficacy/toxicity ratio improvement but also because of the importance of an optimal adherence to oral treatments. The present case series relates the issues of dealing with uncommon and sometimes never described side effects of sunitinib and sorafenib. The first case report deals with grade 3 vomiting during hemodialysis with concurrent administration of sunitinib...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28423613/secreted-grp78-activates-egfr-src-stat3-signaling-and-confers-the-resistance-to-sorafeinib-in-hcc-cells
#13
Rui Li, Gu Yanjiao, He Wubin, Wang Yue, Huang Jianhua, Zheng Huachuan, Su Rongjian, Luan Zhidong
Acquired resistance is a common phenomenon for HCC patients who undergone sorafenib treatment, however the mechanism by which acquired resistance develops remains elusive. In this study, we found that GRP78 could be detected in the serum samples of HCC patients and the conditional medium of multiple HCC cell lines, suggesting that GRP78 is secreted by HCC cells. Further studies showed that secreted GRP78 facilitated the proliferation and inhibited the apoptosis induced by sorafenib both in HCC cell lines and in tumor xenografts...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423574/synergistic-anti-tumor-efficacy-of-sorafenib-and-fluvastatin-in-hepatocellular-carcinoma
#14
Yang Cheng, RongCheng Luo, Hang Zheng, Biao Wang, YaHui Liu, DingLi Liu, JinZhang Chen, WanFu Xu, AiMin Li, Yun Zhu
Drug resistance to sorafenib is common in patients with hepatocellular carcinoma(HCC). We examined the effects of a combination of sorafenib and fluvastatin on HCC using in vitro and in vivo models. The dual treatment induced apoptosis and reduced cellular viability in HCC more effectively than either drug alone. The combination treatment also inhibited activation of hepatic stellate cells, whereas single drug treatments did not. On a molecular level, combined treatment inhibited activation of the MAPK and NF-κB pathways via Toll-like receptor 4 in HCC cells...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423370/transarterial-chemoembolization-combined-with-jie-du-granule-preparation-improves-the-survival-outcomes-of-patients-with-unresectable-hepatocellular-carcinoma
#15
Hetong Zhao, Xiaofeng Zhai, Zhe Chen, Xuying Wan, Lanyu Chen, Feng Shen, Changquan Ling
The aim of the present study was to compare the effectiveness of transarterial chemoembolization (TACE), TACE combined with Jie-du granules (JD), and TACE combined with sorafenib (SOR) for treating patients with unresectable hepatocellular carcinoma (HCC). For this purpose, we conducted a retrospective analysis of data from 266 consecutive patients with unresectable HCC who underwent TACE treatment at the Shanghai Hospital and Eastern Hepatic Surgery Hospital between Jan 2009 and Dec 2010. We prospectively analyzed patient survival and progression times as well as independent predictors, within a follow-up period of 86 months...
April 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28421483/update-on-embolization-therapies-for-hepatocellular-carcinoma
#16
REVIEW
Sirish Kishore, Tamir Friedman, David C Madoff
PURPOSE OF REVIEW: The purpose of the review is to summarize the latest applications for embolotherapy in the management of patients with HCC according to BCLC stage. RECENT FINDINGS: While traditionally reserved for patients with unresectable HCC and stage B disease, there is an important role for embolization therapies in earlier stage patients as an adjunct to ablation, bridging, or downstaging therapy, as a means to improve safety of resection, and potentially as an arterial ablative option in the case of radioembolization...
June 2017: Current Oncology Reports
https://www.readbyqxmd.com/read/28420805/immunotherapeutic-approaches-for-hepatocellular-carcinoma
#17
Vito Longo, Antonio Gnoni, Andrea Casadei Gardini, Salvatore Pisconti, Antonella Licchetta, Mario Scartozzi, Riccardo Memeo, Vincenzo Ostilio Palmieri, Giuseppe Aprile, Daniele Santini, Patrizia Nardulli, Nicola Silvestris, Oronzo Brunetti
Hepatocellular carcinoma (HCC) is a cancer with a high mortality rate due to the fact that the diagnosis usually occurs at anadvanced stage. Even in case of curative surgical treatment, recurrence is common. Sorafenib and regorafenib are the only therapeutic agents that have been demonstrated to be effective in advanced HCC, thus novel curative approaches are urgently needed. Recent studies focus on the role of immune system in HCC. In fact, the unique immune response in the liver favors tolerance, which can represent a real challenge for conventional immunotherapy in these patients...
February 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28420393/medical-treatment-of-mammary-desmoid-type-fibromatosis-which-benefit
#18
Louise Scheer, Massimo Lodi, Sébastien Molière, Jean-Emmanuel Kurtz, Carole Mathelin
BACKGROUND: Breast fibromatosis is a rare disease characterized by monoclonal fibroblast proliferation. It has no ability to metastasize but has a high local recurrence rate and often infiltrates surrounding tissues. Surgical treatment is the reference, but recently, new targeted therapies have emerged. We report an original case of a patient with breast fibromatosis who received exclusive medical treatment. Our aim was to analyze these treatments based on the clinical and radiological outcome, iatrogenic effects, and pharmacological action...
April 18, 2017: World Journal of Surgical Oncology
https://www.readbyqxmd.com/read/28418927/transarterial-chemoembolization-combined-with-computed-tomography-guided-125iodine-implantation-enhances-survival-in-hepatocellular-carcinoma-patients-with-portal-vein-tumor-thrombus
#19
Hong Tao Hu, Jun Peng Luo, Hai-Liang Li, Chen Yang Guo, Quan Jun Yao, Xiang Geng, Li Jiang
We conducted a retrospective study to evaluate the safety and efficacy of transarterial chemoembolization (TACE) combined with computed tomography-guided 125iodine implantation (TACE-125iodine) in hepatocellular carcinoma (HCC) patients with type B portal vein tumor thrombus (PVTT). From medical records, we determined that 50 patients who received 125iodine implantation 4-7 days after the first TACE session showed better survival than 50 patients who received only TACE (median survival, 13.1 vs. 6.0 months; P<0...
March 23, 2017: Oncotarget
https://www.readbyqxmd.com/read/28415783/mass-spectral-analysis-of-the-multikinase-inhibitor-bzg-and-its-metabolites-and-analysis-of-their-binding-to-vascular-endothelial-growth-factor-receptor-2
#20
Yan Lou, Wenqi Qiu, Zhe Wu, Qian Wang, Yunqing Qiu, Su Zeng
We previously showed that BZG is a novel multitarget kinase inhibitor, which inhibited hepatocellular carcinoma in vivo and in vitro. In the present study, we used ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF MS) to characterize BZG and its metabolites generated in vivo. The probable metabolic mechanism was further confirmed by analysis of Phase I and Phase II metabolism in liver microsomes and with recombinant enzymes. In addition, the binding affinities of BZG metabolites to vascular endothelial growth factor receptor 2 (VEGFR2) were predicted using electronic high throughput screening (eHiTS)...
March 16, 2017: Oncotarget
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