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https://www.readbyqxmd.com/read/28821631/6-methoxyethylamino-numonafide-inhibits-hepatocellular-carcinoma-xenograft-growth-as-a-single-agent-and-in-combination-with-sorafenib
#1
Yanning Liu, Guohua Lou, John T Norton, Chen Wang, Irawati Kandela, Shuai Tang, Nathaniel I Shank, Pankaj Gupta, Min Huang, Michael J Avram, Richard Green, Andrew Mazar, Daniel Appella, Zhi Chen, Sui Huang
Hepatocellular carcinoma (HCC) is the third leading form of cancer worldwide, and its incidence is increasing rapidly in the United States, tripling over the past 3 decades. The current chemotherapeutic strategies against localized and metastatic HCC are ineffective. Here we report that 6-methoxyethylamino-numonafide (MEAN) is a potent growth inhibitor of murine xenografts of 2 human HCC cell lines. At the same dose and with the same treatment strategies, MEAN was more efficacious in inhibiting tumor growth in mice than sorafenib, the only approved drug for HCC...
August 17, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28819429/map2k1-mutation-in-colorectal-cancer-patients-therapeutic-challenge-using-patient-derived-tumor-cell-lines
#2
J E Kim, K K Kim, S Y Kim, J Lee, S H Park, J O Park, Y S Park, H Y Lim, W K Kang, S T Kim
BACKGROUND: The MAP2K1 K57T mutation is known to be a potential mechanism of primary and secondary resistance to EGFR inhibitors in metastatic colorectal cancer (CRC) and has also been reported to promote resistance to BRAF and MEK inhibitors. It is important to overcome therapeutic resistance to EGFR inhibitors to improve the treatment outcomes of metastatic CRC. METHODS: We established patient-derived tumor cells (PDCs) from metastatic lesions that newly appeared during treatment with a BRAF inhibitor (LGX-818) plus an EGFR inhibitor (cetuximab) in a patient with BRAF-mutant CRC...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28819398/clinical-impact-of-vitamin-k-dosing-on-sorafenib-treatment-for-hepatocellular-carcinoma
#3
Yoshimichi Haruna, Noriko Hasegawa, Kazuho Imanaka, Seiichi Kawamoto, Atsuo Inoue
Background: Some researchers have suggested that vitamin K enhances the antitumor effect of sorafenib for hepatocellular carcinoma (HCC) in vitro and in vivo. In this study, we examined the clinical impact of vitamin K dosing for sorafenib treatment. Methods: Twenty-nine out of 65 patients treated with sorafenib for HCC were simultaneously dosed with vitamin K. We retrospectively investigated progression-free survival (PFS) and overall survival (OS) in the vitamin K-dosed group and sorafenib alone group. We also examined the changes in serum des-γ-carboxy prothrombin (DCP) levels, which vitamin K is involved with...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28819176/use-of-biocompatible-sorafenib-gold-nanoconjugates-for-reversal-of-drug-resistance-in-human-hepatoblatoma-cells
#4
Sandeep Kumar Vishwakarma, Priyanka Sharmila, Avinash Bardia, Lakkireddy Chandrakala, N Raju, G Sravani, B V S Sastry, Md Aejaz Habeeb, Aleem Ahmed Khan, Marshal Dhayal
The present study identifies the potential of highly biocompatible SF-GNP nano-conjugate to enhance the chemotherapeutic response to combat drug resistance in cancer cells. We developed a stable colloidal suspension of sorafenib-gold nanoconjugate (SF-GNP) of <10 nm size in aqueous medium for reverting the cancer drug resistance in SF-resistant HepG2 cells in a 3D ex-vivo model system. In-vivo biocompatibility assay of SF-GNPs showed absence of systemic toxicological effects including hematological, biochemical and histological parameters...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28817373/cabozantinib-as-salvage-therapy-for-patients-with-tyrosine-kinase-inhibitor-refractory-differentiated-thyroid-cancer-results-of-a-multicenter-phase-ii-international-thyroid-oncology-group-trial
#5
Maria E Cabanillas, Jonas A de Souza, Susan Geyer, Lori J Wirth, Michael E Menefee, Stephen V Liu, Komal Shah, John Wright, Manisha H Shah
Purpose Sorafenib and lenvatinib are oral multikinase inhibitors targeting vascular endothelial growth factor receptor (VEGFR) and approved for radioiodine (RAI)-refractory differentiated thyroid cancer (DTC). However, there are no approved second- or third-line therapies. MET is implicated in resistance to VEGFR inhibitors. Cabozantinib is an oral multikinase inhibitor targeting MET in addition to VEGFR and is approved for medullary thyroid cancer. In a phase I study of cabozantinib, five of eight patients with DTC previously treated with a VEGFR-targeted therapy had an objective response to cabozantinib...
August 17, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28815645/lenalidomide-as-second-line-therapy-for-advanced-hepatocellular-carcinoma-exploration-of-biomarkers-for-treatment-efficacy
#6
Y-Y Shao, B-B Chen, D-L Ou, Z-Z Lin, C-H Hsu, M-J Wang, A-L Cheng, C Hsu
BACKGROUND: Lenalidomide has immunomodulatory and anti-angiogenic effects and showed moderate anti-tumour efficacy in patients with. advanced hepatocellular carcinoma (HCC) AIM: To explore potential biomarkers of lenalidomide efficacy as second-line therapy for HCC. METHODS: Eligible patients were diagnosed with advanced HCC, documented progression on sorafenib, and Child-Pugh class A liver function. Patients received 25 mg/day lenalidomide orally on days 1-21 every 4 weeks...
August 17, 2017: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28811106/questiomycin-a-stimulates-sorafenib-induced-cell-death-via-suppression-of-glucose-regulated-protein-78
#7
Kayo Machihara, Hidenori Tanaka, Yoshihiro Hayashi, Ichiro Murakami, Takushi Namba
Hepatocellular carcinoma (HCC) is one of the most difficult cancers to treat owing to the lack of effective chemotherapeutic methods. Sorafenib, the first-line and only available treatment for HCC, extends patient overall survival by several months, with a response rate below 10%. Thus, the identification of an agent that enhances the anticancer effect of sorafenib is critical for the development of therapeutic options for HCC. Endoplasmic reticulum (ER) stress response is one of the methods of sorafenib-induced cell death...
August 12, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28808589/anti-angiogenic-agents-for-the-treatment-of-solid-tumors-potential-pathways-therapy-and-current-strategies-a-review
#8
REVIEW
Ahmed M Al-Abd, Abdulmohsin J Alamoudi, Ashraf B Abdel-Naim, Thikryat A Neamatallah, Osama M Ashour
Recent strategies for the treatment of cancer, other than just tumor cell killing have been under intensive development, such as anti-angiogenic therapeutic approach. Angiogenesis inhibition is an important strategy for the treatment of solid tumors, which basically depends on cutting off the blood supply to tumor micro-regions, resulting in pan-hypoxia and pan-necrosis within solid tumor tissues. The differential activation of angiogenesis between normal and tumor tissues makes this process an attractive strategic target for anti-tumor drug discovery...
November 2017: Journal of Advanced Research
https://www.readbyqxmd.com/read/28808038/the-phosphatidylinositol-3-kinase-pathway-as-a-potential-therapeutic-target-in-bladder-cancer
#9
Shuxiong Zeng, Yanjun Zhu, Ai-Hong Ma, Weimin Yu, Hongyong Zhang, Tzu-Yin Lin, Wei Shi, Clifford G Tepper, Paul T Henderson, Susan Airhart, Jianming Guo, Chuanliang Xu, Ralph de Vere White, Chong-Xian Pan
PURPOSE: Activation of the phosphatidylinositol 3-kinase (PI3K) pathway occurs in over 40% of bladder urothelial cancers. The aim of this study is to determine the therapeutic potential, the underlying action and resistant mechanisms of drugs targeting the PI3K pathway. EXPERIMENTAL DESIGN: Urothelial cancer cell lines and patient-derived xenografts (PDXs) were analyzed for alterations of the PI3K pathway and for their sensitivity to the small molecule inhibitor pictilisib alone and in combination with cisplatin and/or gemcitabine...
August 14, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28801777/an-internally-validated-new-clinical-and-inflammation-based-prognostic-score-for-patients-with-advanced-hepatocellular-carcinoma-treated-with-sorafenib
#10
R Diaz-Beveridge, G Bruixola, D Lorente, J Caballero, E Rodrigo, Á Segura, D Akhoundova, A Giménez, J Aparicio
BACKGROUND: Sorafenib is a standard treatment for patients (pts) with advanced hepatocellular carcinoma (aHCC), although the clinical benefit is heterogeneous between different pts groups. Among novel prognostic factors, a low baseline neutrophil-to-lymphocyte ratio (bNLR) and early-onset diarrhoea have been linked with a better prognosis. PURPOSE: To identify prognostic factors in pts with aHCC treated with 1st-line sorafenib and to develop a new prognostic score to guide management...
August 11, 2017: Clinical & Translational Oncology
https://www.readbyqxmd.com/read/28797997/hepatocellular-carcinoma-peritoneal-metastasis-role-of-cytoreductive-surgery-and-hyperthermic-intraperitoneal-chemotherapy-hipec
#11
John Spiliotis, Georgios Nikolaou, Nikolaos Kopanakis, Dimitra Vassiliadou, Alexios Terra, Elias Efstathiou
INTRODUCTION: Peritoneal dissemination of hepatocellular carcinoma (HCC) is a rare presentation with an incidence of 2-6%. The most common cause of peritoneal deposits is a ruptured HCC that results in tumor spillage into the peritoneal cavity. The overall incidence of spontaneous ruptures of HCC ranges from 5 to 15% and carries a high mortality rate of up to 50%. Other factors influencing peritoneal dissemination are the lymph node metastasis and the direct diaphragmatic invasion and there is no significant association with past history of FNAB, or percutaneous RFA or ethanol injection and lung or adrenal metastasis...
May 2017: Gulf Journal of Oncology
https://www.readbyqxmd.com/read/28797231/survival-benefit-of-transarterial-chemoembolization-in-patients-with-metastatic-hepatocellular-carcinoma-a-single-center-experience
#12
Dominik Bettinger, Renan Spode, Nicolas Glaser, Nico Buettner, Tobias Boettler, Christoph Neumann-Haefelin, Thomas Baptist Brunner, Eleni Gkika, Lars Maruschke, Robert Thimme, Michael Schultheiss
BACKGROUND: As prognosis of patients with metastatic hepatocellular carcinoma (HCC) is mainly determined by intrahepatic HCC progression, local treatment with TACE may result in improved OS, although it is not recommended. The purpose of this study was to analyze retrospectively the efficacy of TACE and its impact on OS in patients with metastatic hepatocellular carcinoma (HCC). METHODS: Two hundred and fifteen patients with metastatic HCC who were treated at our Liver Center between 2003 and 2014 were included in this retrospective analysis...
August 10, 2017: BMC Gastroenterology
https://www.readbyqxmd.com/read/28795750/supramolecular-alleviation-of-cardiotoxicity-of-a-small-molecule-kinase-inhibitor
#13
Xue Yang, Qiaoxian Huang, David Bardelang, Chunming Wang, Simon M Y Lee, Ruibing Wang
Small-molecule kinase inhibitors (SMKIs) have been widely used in the treatment of a variety of cancers due to their clinically demonstrated efficacy. However, the use of some SMKIs, such as sorafenib (SO), has been plagued by their cardiotoxicity that has been frequently observed in treated patients. Herein we report that the encapsulation of SO by a synthetic receptor cucurbit[7]uril (CB[7]) alleviated the inherent cardiotoxicity of SO, as demonstrated in an in vivo zebrafish model. Moreover, the anti-cancer activity of SO was well preserved, upon its encapsulation by CB[7], as demonstrated by both in vitro and in vivo cancer/angiogenesis models...
August 10, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/28795053/transarterial-chemoembolization-for-the-treatment-of-hepatocellular-carcinoma-a-review
#14
REVIEW
Rodolfo Sacco, Gherardo Tapete, Natalia Simonetti, Rossella Sellitri, Veronica Natali, Sara Melissari, Giuseppe Cabibbo, Lilia Biscaglia, Giampaolo Bresci, Luca Giacomelli
According to the current European Association for the Study of Liver guidelines, transarterial chemoembolization (TACE) is the recommended first-line therapy for patients with intermediate-stage (Barcelona Clinic Liver Cancer-B class) hepatocellular carcinoma (HCC). The efficacy of this therapy is supported by robust evidence; however, there is still a lack of standardization in treatment methodology, and TACE protocols are widely variable. Moreover, TACE can be associated with a number of contraindications...
2017: Journal of Hepatocellular Carcinoma
https://www.readbyqxmd.com/read/28794043/sorafenib-impedes-rift-valley-fever-virus-egress-by-inhibiting-valosin-containing-protein-function-in-the-cellular-secretory-pathway
#15
Ashwini Brahms, Rajini Mudhasani, Chelsea Pinkham, Krishna Kota, Farooq Nassar, Rouzbeh Zamani, Sina Bavari, Kylene Kehn-Hall
There is an urgent need for therapeutic development to combat Rift Valley fever virus (RVFV) infections, which causes devastating disease in both humans and animals. In an effort to repurpose drugs for RVFV treatment, our previous studies screened a library of FDA-approved drugs. The most promising candidate identified was the hepatocellular and renal cell carcinoma drug, sorafenib. Mechanism of action studies indicated sorafenib targeted a late stage in virus infection and caused a buildup of virions within cells...
August 9, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28792525/a-data-mining-approach-for-identifying-pathway-gene-biomarkers-for-predicting-clinical-outcome-a-case-study-of-erlotinib-and-sorafenib
#16
David G Covell
A novel data mining procedure is proposed for identifying potential pathway-gene biomarkers from preclinical drug sensitivity data for predicting clinical responses to erlotinib or sorafenib. The analysis applies linear ridge regression modeling to generate a small (N~1000) set of baseline gene expressions that jointly yield quality predictions of preclinical drug sensitivity data and clinical responses. Standard clustering of the pathway-gene combinations from gene set enrichment analysis of this initial gene set, according to their shared appearance in molecular function pathways, yields a reduced (N~300) set of potential pathway-gene biomarkers...
2017: PloS One
https://www.readbyqxmd.com/read/28792505/fluorescence-imaging-of-bombesin-and-transferrin-receptor-expression-is-comparable-to-18f-fdg-pet-in-early-detection-of-sorafenib-induced-changes-in-tumor-metabolism
#17
Jen-Chieh Tseng, Nara Narayanan, Guojie Ho, Kevin Groves, Jeannine Delaney, Bagna Bao, Jun Zhang, Jeffrey Morin, Sylvie Kossodo, Milind Rajopadhye, Jeffrey D Peterson
Physical measurement of tumor volume reduction is the most commonly used approach to assess tumor progression and treatment efficacy in mouse tumor models. However, it is relatively insensitive, and often requires long treatment courses to achieve gross physical tumor destruction. As alternatives, several non-invasive imaging methods such as bioluminescence imaging (BLI), fluorescence imaging (FLI) and positron emission tomography (PET) have been developed for more accurate measurement. As tumors have elevated glucose metabolism, 18F-fludeoxyglucose (18F-FDG) has become a sensitive PET imaging tracer for cancer detection, diagnosis, and efficacy assessment by measuring alterations in glucose metabolism...
2017: PloS One
https://www.readbyqxmd.com/read/28792132/down-regulation-of-tgf-%C3%AE-expression-sensitizes-the-resistance-of-hepatocellular-carcinoma-cells-to-sorafenib
#18
Dongxu Kang, Zhezhu Han, Geun Hyeok Oh, Yeonsoo Joo, Hye Jin Choi, Jae J Song
PURPOSE: Sorafenib, a multikinase inhibitor, is the standard therapy for patients with advanced-stage hepatocellular carcinoma (HCC). However, resistance develops to the treatment, therefore, we tried to unravel the underlying mechanism in the resistance of HCC cells to sorafenib via the development of more effective therapeutic strategies. MATERIALS AND METHODS: Various liver cancer cell lines were treated with either sorafenib only or with sorafenib after infection of adenovirus expressing short hairpin RNA (shRNA) against transforming growth factor-β (TGF-β) and p38 activity was examined using western blotting...
September 2017: Yonsei Medical Journal
https://www.readbyqxmd.com/read/28789709/comparison-of-efficacy-safety-and-quality-of-life-between-sorafenib-and-sunitinib-as-first-line-therapy-for-chinese-patients-with-metastatic-renal-cell-carcinoma
#19
Wen Cai, Wen Kong, Baijun Dong, Jin Zhang, Yonghui Chen, Wei Xue, Yiran Huang, Lixin Zhou, Jiwei Huang
BACKGROUND: Sorafenib and sunitinib are widely used as first-line targeted therapy for metastatic renal cell carcinoma (mRCC) in China. This study aimed to compare the efficacy, safety, and quality of life (QoL) in Chinese mRCC patients treated with sorafenib and sunitinib as first-line therapy. METHODS: Clinical data of patients with mRCC who received sorafenib (400 mg twice daily; 4 weeks) or sunitinib (50 mg twice daily; on a schedule of 4 weeks on treatment followed by 2 weeks off) were retrieved...
August 8, 2017: Chinese Journal of Cancer
https://www.readbyqxmd.com/read/28781818/significance-of-psoas-muscle-thickness-as-an-indicator-of-muscle-atrophy-in-patients-with-hepatocellular-carcinoma-treated-with-sorafenib
#20
Mio Yamashima, Hisamitsu Miyaaki, Takuya Honda, Hidetaka Shibata, Satoshi Miuma, Naota Taura, Kazuhiko Nakao
Sarcopenia has been reported to be associated with the prognosis of patients with liver cirrhosis and hepatocellular carcinoma (HCC). The aim of the present study was to determine whether sarcopenia was associated with the prognosis of patients with HCC treated with sorafenib. A total of 40 patients with HCC who were treated with sorafenib were evaluated. As an indicator of skeletal muscle mass, transverse psoas muscle thickness (TPMT) was measured on computed tomography images at the level of the umbilicus prior to treatment initiation and after 1-3 months of treatment...
September 2017: Molecular and Clinical Oncology
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