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Sorafenib

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https://www.readbyqxmd.com/read/28717362/treatment-of-advanced-hepatocellular-carcinoma-after-failure-of-sorafenib-treatment-subsequent-or-additional-treatment-interventions-contribute-to-prolonged-survival-postprogression
#1
Masaaki Kondo, Kazushi Numata, Koji Hara, Akito Nozaki, Hiroyuki Fukuda, Makoto Chuma, Shin Maeda, Katsuaki Tanaka
BACKGROUND: Sorafenib is a first-line treatment option for advanced hepatocellular carcinoma (HCC) patients; however, survival predictors upon progression have not been well characterized. In the present study, we aimed to show the efficacy of multidisciplinary therapy for patients who had failed to respond to sorafenib treatment. METHODS: Among 146 BCLC stage B or C HCC patients treated with sorafenib monotherapy between July 2009 and August 2014, the first radiological progression according to the modified RECIST was identified in 71 patients; factors predicting overall survival (OS) and survival postprogression (SPP) were analyzed in these patients...
2017: Gastroenterology Research and Practice
https://www.readbyqxmd.com/read/28715649/excellent-response-to-anti-pd-1-therapy-in-a-patient-with-hepatocellular-carcinoma-case-report-and-review-of-literature
#2
Hirva Mamdani, Howard Wu, Bert H O'Neil, Amikar Sehdev
Hepatocellular carcinoma (HCC) is an aggressive cancer associated with high mortality worldwide. HCC develops in the setting of underlying cirrhosis due to chronic liver disease. Surgery is usually considered the treatment of choice for early disease; however, most patients have locally advanced or metastatic HCC at diagnosis in which case treatments are limited. Immune checkpoint blockade of programmed death receptor-1 (PD-1) pathway offers a potential treatment strategy based on the encouraging results of the phase I/II trial of nivolumab (Checkmate 040 trial)...
May 2017: Discovery Medicine
https://www.readbyqxmd.com/read/28714104/chronic-inflammation-elicited-liver-progenitor-cell-conversion-to-liver-cancer-stem-cell-with-clinical-significance
#3
Xiao-Feng Li, Cheng Chen, Dai-Min Xiang, Le Qu, Wen Sun, Xin-Yuan Lu, Teng-Fei Zhou, Shu-Zhen Chen, Bei-Fang Ning, Zhuo Cheng, Ming-Yang Xia, Wei-Feng Shen, Wen Yang, Wen Wen, Terence Kin Wah Lee, Wen-Ming Cong, Hong-Yang Wang, Jin Ding
The substantial heterogeneity and hierarchical organization in liver cancer supports the theory of liver cancer stem cell (LCSC). However, the relationship between chronic hepatic inflammation and LCSC generation remains obscure. Here we observed a close correlation between aggravated inflammation and liver progenitor cell (LPC) propagation in the cirrhotic liver of rats exposed to diethylnitrosamine. LPCs isolated from the rat cirrhotic liver initiated subcutaneous liver cancers in NOD/SCID mice, suggesting the malignant transformation of LPC toward LCSC...
July 17, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28713155/hypoxia-induces-universal-but-differential-drug-resistance-and-impairs-anticancer-mechanisms-of-5-fluorouracil-in-hepatoma-cells
#4
Jing-Qiu Li, Xian Wu, Lu Gan, Xiang-Liang Yang, Ze-Hong Miao
Hepatocellular carcinoma (HCC) is one of the most refractory cancers. The mechanisms by which hypoxia further aggravates therapeutic responses of advanced HCC to anticancer drugs remain to be clarified. Here, we report that hypoxia (1% O2) caused 2.55-489.7-fold resistance to 6 anticancer drugs (sorafenib, 5-fluorouracil [5-FU], gemcitabine, cisplatin, adriamycin and 6-thioguanine) in 3 HCC cell lines (BEL-7402, HepG2 and SMMC-7721). Among the 6 drugs, sorafenib, the sole one approved for HCC therapy, inhibited proliferation with little influence from hypoxia and displayed the smallest variation among the 3 HCC cell lines tested...
July 17, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28712860/tolerance-and-outcomes-of-sorafenib-in-elderly-patients-treated-for-advanced-hepatocellular-carcinoma
#5
Nicolas Williet, Léa Clavel, Aurélie Bourmaud, Céline Verot, Nadia Bouarioua, Xavier Roblin, Philippe Merle, Jean-Marc Phelip
INTRODUCTION: Use of sorafenib remains debated in elderly patients treated for advanced hepatocellular carcinoma (HCC). METHODS: This was a bicentric retrospective study including all patients ≥75years and treated with sorafenib for advanced HCC between January 2010 and March 2014. RESULTS: Of the 51 patients included (median age: 78 years, range: 75-92; performance status (PS) 0-1: 98%; cirrhosis: 88.2%; Child-Pugh A: 95.6%) all experienced at least one adverse event (AE)...
June 23, 2017: Digestive and Liver Disease
https://www.readbyqxmd.com/read/28712319/primary-liver-cancer-genome-sequencing-translational-implications-and-challenges
#6
Demosthenes E Ziogas, Ioannis D Kyrochristos, Georgios K Glantzounis, Dimitrios Christodoulou, Evangelos Felekouras, Dimitrios H Roukos
The prognosis of primary liver cancer (PLC) remains poor and is explained by the slow progress in understanding the molecular pathways driving tumorigenesis, therapeutic resistance and relapse. For early PLCs, complete surgical resection is the only effective treatment, with sorafenib and, more recently, regorafenib prolonging overall survival by a few months. Areas covered: Application of next-generation sequencing (NGS), including targeted NGS (tNGS), whole-exome sequencing (WES), whole-genome sequencing (WGS) and RNA sequencing (RNAseq), on clinical samples from patients with hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) could aid in comprehending tumorigenesis, genetic and genomic heterogeneity, as well as developing molecular classifications for specialized targeted therapy...
July 17, 2017: Expert Review of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28712281/extraordinary-radiation-super-sensitivity-accompanying-with-sorafenib-combination-therapy-what-lies-beneath
#7
Jayoung Lee, Ju Hye Lee, Hanbin Yoon, Ho Jeong Lee, Hosang Jeon, Jiho Nam
Primary liver tumor, especially hepatocellular carcinoma (HCC), is a common cause of cancer death worldwide. The incidence is generally higher in Asian countries than in western countries. Carcinogenesis of HCC is often associated with hepatitis viral infections. Current standard treatment of HCC is surgical resection or transplantation in patients with early stage disease. However, the patient with advanced stage disease, surgical resection is often limited. Sorafenib or other treatment modalities are not so effective as well...
June 2017: Radiation Oncology Journal
https://www.readbyqxmd.com/read/28706578/systemic-treatment-of-hepatocellular-carcinoma-past-present-and-future
#8
REVIEW
Esther Una Cidon
Hepatocellular carcinoma (HCC) is a common neoplasia which represents the second leading cause of cancer related death. Most cases occur in developing countries, but its incidence is rising in Western countries due to hepatitis C. Although hepatitis therapies have evolved and the HCC screening has increased in several areas, 40% present with advanced disease which is only amenable for palliative systemic treatment. HCC continues posing a challenge, in part due to the inherent chemoresistance of this neoplasia, the pharmacologic challenges due to an ill liver, difficulty in assessing radiological responses accurately, etc...
June 28, 2017: World Journal of Hepatology
https://www.readbyqxmd.com/read/28706336/palmoplantar-exfoliation-due-to-chloroquine
#9
Pragya Ashok Nair, Trusha Patel
Chloroquine is the drug very frequently used for the treatment of malaria. It is also used in amebiasis, rheumatoid arthritis, and various dermatological conditions. Chloroquine can cause muscle problems, loss of appetite, and diarrhea as a side effect. Cutaneous toxicity includes pruritus, hair loss, photosensitivity, and color changes. Exfoliation of skin over palms and soles is caused by chemotherapeutic drugs such as axitinib, fluorouracil, idarubicin, doxorubicin, sunitinib, sorafenib, and paclitaxel. Here, a case of a 40-year-old female is presented who developed palmoplantar exfoliation with depigmentation after taking chloroquine...
March 2017: Indian Journal of Pharmacology
https://www.readbyqxmd.com/read/28699238/increased-matrix-stiffness-promotes-tumor-progression-of-residual-hepatocellular-carcinoma-after-insufficient-heat-treatment
#10
Rui Zhang, Min Ma, Gang Dong, Rong-Rong Yao, Jing-Huan Li, Qiong-Dan Zheng, Yin-Ying Dong, Hui Ma, Dong-Mei Gao, Jie-Feng Cui, Zheng-Gang Ren, Rong-Xin Chen
The aggravated behaviors of hepatocellular carcinoma (HCC) will occur after inadequate thermal ablation. However, its underlying mechanisms are not fully understood. Here, we assessed whether the increased matrix stiffness after thermal ablation could promote the progression of residual HCC. Heat-treated residual HCC cells were cultured on the tailorable 3D gel with different matrix stiffness simulating the changed physical environment after thermal ablation and then were explored the mechanical alterations of matrix stiffness on cell phenotypes...
July 12, 2017: Cancer Science
https://www.readbyqxmd.com/read/28698202/sorafenib-in-patients-with-hepatocellular-carcinoma-results-of-the-observational-insight-study
#11
Tom M Ganten, Rudolf E Stauber, Eckardt Schott, Peter Malfertheiner, Robert Buder, Peter R Galle, Thomas Göhler, Matthias Walther, Ronald Koschny, Guido Gerken
Sorafenib is the only currently approved systemic therapy for advanced hepatocellular carcinoma (HCC). We aimed to evaluate the safety and efficacy of sorafenib therapy in patients with HCC under real-life conditions regarding patient, tumor characteristics and any adverse events at study entry and at follow-up visits every 2-4 months. <br /><br />Experimental Design: The present INSIGHT study is a non-interventional, prospective, multicenter, observational study performed in 124 sites across Austria and Germany between 2008 and 2014...
July 11, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28693290/therapy-with-transcutaneous-administration-of-imiquimod-combined-with-oral-administration-of-sorafenib-suppresses-renal-cell-carcinoma-growing-in-an-orthotopic-mouse-model
#12
Takashi Karashima, Keiko Udaka, Mayumi Niimura, Katsuhide Suzuki, Hiroto Osakabe, Tsutomu Shimamoto, Satoshi Fukata, Keiji Inoue, Naoto Kuroda, Motoharu Seiki, Taro Shuin
Imiquimod is an imidazoquinoline immune response modifier that is used in antiviral and antiallergic creams. Combination therapy using transcutaneous imiquimod and oral sorafenib was previously demonstrated to reduce the tumor burden of renal cell carcinoma growing cutaneously in a mouse model. In the present study, an orthotopic mouse model was used to investigate whether combined treatment with oral sorafenib and transcutaneous imiquimod inhibited renal cell carcinoma growing in the kidney. Kidneys of female BALB/c mice were orthotopically implanted with RENCA mouse kidney cancer cells, and the mice were transcutaneously treated with cream containing imiquimod and/or with orally administered sorafenib 5 days following cell implantation...
July 2017: Oncology Letters
https://www.readbyqxmd.com/read/28693200/sorafenib-induced-alteration-of-protein-glycosylation-in-hepatocellular-carcinoma-cells
#13
Tianhua Liu, Riqiang Liu, Shu Zhang, Kun Guo, Qinle Zhang, Wei Li, Yinkun Liu
Sorafenib is a multikinase inhibitor and is effective in treating hepatocellular carcinoma (HCC). However, it remains unknown whether sorafenib induces the alteration of protein glycosylation. The present study treated HCC MHCC97L and MHCC97H cells with a 50% inhibitory concentration of sorafenib. Following this treatment, alteration of protein glycosylation was detected using a lectin microarray. Compared with the controls, the binding capacity of glycoproteins extracted from sorafenib-treated HCC cells to the lectins Bauhinia purpurea lectin, Dolichos biflorus agglutinin, Euonymus europaeus lectin, Helix aspersa lectin, Helix pomatia lectin, Jacalin, Maclura pomifera lectin and Vicia villosa lectin were enhanced; while, the binding capacities to the lectins Caragana arborescens lectin, Lycopersicon esculentum lectin, Limulus polyphemus lectin, Maackia amurensis lecin I, Phaseolus vulgaris leucoagglutinin, Ricinus communis agglutinin 60, Sambucus nigra lectin and Solanum tuberosum lectin were reduced (spot intensity median/background intensity median ≥2, P<0...
July 2017: Oncology Letters
https://www.readbyqxmd.com/read/28693178/presurgical-neoadjuvant-targeted-molecular-therapy-for-kidney-cancer-with-concomitant-vena-cava-tumor-embolus-a-clinical-study
#14
Gang Guo, Wei Cai, Hongzhao Li, Jiangping Gao, Xin Ma, Jun Dong, Weijun Fu, Xu Zhang
The present study aimed to investigate presurgical neoadjuvant targeted therapy for patients with kidney cancer and vena cava tumor embolus, in order to examine its indications, therapeutic effects and optimal timing of surgery. Between June 2009 and June 2014, 12 patients from The People's Liberation Army General Hospital (Beijing, China) were diagnosed with kidney cancer with superior vena cava tumor embolus, and received presurgical neoadjuvant targeted therapy (sorafenib 400 mg twice a day or sunitinib 50 mg/day) for a median of 13...
July 2017: Oncology Letters
https://www.readbyqxmd.com/read/28691138/the-importance-of-parameters-mpv-mpv-thrombocyte-ratio-and-neutrophil-lymphocyte-ratio-in-sorafenib-treatment-response-of-patients-with-hepatocellular-cancer
#15
Ali Oğul, Berksoy Şahin, Ferit Kuşçu, Onur Taktakoğlu, Abdullah Evren Yetişir, Mahmut Büyükşimşek, Cem Mirili, Serkan Gökçay, M Gökhan Gök, Pınar Kum
No abstract text is available yet for this article.
July 10, 2017: Journal of Gastrointestinal Cancer
https://www.readbyqxmd.com/read/28687627/phase-ii-trial-of-sorafenib-in-combination-with-capecitabine-in-patients-with-hepatocellular-carcinoma-inst-08-20
#16
Yehuda Patt, Cristhiam Rojas-Hernandez, Houman Mohammad Fekrazad, Pranshu Bansal, Fa Chyi Lee
LESSONS LEARNED: There continues to be a lack of systemic options for advanced hepatocellular carcinoma (HCC); sorafenib and, very recently, regorafenib are the only approved options. There exists a potential to combine sorafenib with chemotherapeutic agents shown to be active in HCC, such as capecitabine, safely.Good tumor response was observed, with objective improvement in a few patients seldom seen by single agent sorafenib; however, because of the limited number of patients, meaningful conclusions on survival cannot be drawn...
July 7, 2017: Oncologist
https://www.readbyqxmd.com/read/28687477/prognostic-factors-and-predictors-of-sorafenib-benefit-in-patients-with-hepatocellular-carcinoma-analysis-of-two-phase-3-studies
#17
Jordi Bruix, Ann-Lii Cheng, Gerold Meinhardt, Keiko Nakajima, Yoriko De Sanctis, Josep Llovet
BACKGROUND AND AIMS: Sorafenib, an oral multikinase inhibitor, significantly prolonged overall survival (OS) versus placebo in patients with unresectable hepatocellular carcinoma (HCC) in two phase 3 studies, SHARP (Sorafenib HCC Assessment Randomized Protocol) and Asia-Pacific (AP). To assess prognostic factors for HCC and predictive factors of sorafenib benefit, we conducted a pooled exploratory analysis from these placebo-controlled phase 3 studies. METHODS: To identify potential prognostic factors for OS, univariate and multivariate (MV) analyses were performed for baseline variables by Cox proportional hazards model...
July 4, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28687430/management-of-the-lateral-neck-in-well-differentiated-thyroid-cancer
#18
REVIEW
J R Cracchiolo, R J Wong
Lateral neck lymph node metastases in well differentiated thyroid cancer are common, ranging from 30% to 60%, with the majority of these foci identifiable only as microscopic deposits. A skilled ultrasound evaluation of the lymph nodes in the lateral neck is recommended for all patients presenting with newly diagnosed thyroid cancer undergoing surgical management. Ultrasound guided fine needle aspiration biopsy may be used to cytologically confirm suspected lateral neck nodal metastases prior to surgery. For patients with large volume nodal disease, extranodal extension, or multiple nodal metastases, computed tomography (CT) scan of the neck with contrast is an important additional imaging modality to accurately localize disease prior to surgery...
June 22, 2017: European Journal of Surgical Oncology
https://www.readbyqxmd.com/read/28687354/aspirin-disrupts-the-mtor-raptor-complex-and-potentiates-the-anti-cancer-activities-of-sorafenib-via-mtorc1-inhibition
#19
Danni Sun, Xiaoyang Dai, Juan Yan, Rongrui Wei, Aijun Shen, Min Huang, Xun Huang, Jian Ding, Meiyu Geng
Aspirin is associated with a reduced risk of cancer and delayed progression of malignant disease. Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK)-mTOR signaling is believed to partially contribute to these anticancer effects, although the mechanism is unclear. In this study, we investigated the detailed molecular mechanism underlying the effects of aspirin on AMPK-mTOR signaling and describe a mechanism-based rationale for the use of aspirin in cancer treatment. We found that aspirin inhibited mTORC1 signaling in AMPK-dependent and -independent manners...
July 5, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28685689/arylurea-derivatives-a-class-of-potential-cancer-targeting-agents
#20
Jia-Nian Chen, De-Wen Wu, Ting Li, Kang-Jian Yang, Li Cheng, Zu-Ping Zhou, Shi-Ming Pu, Wan-Hua Lin
Arylurea derivatives, an important class of small molecules, have received considerable attention in recent years due to their wide range of biological applications. Various molecular targeted agents with arylurea scaffold as potential enzyme/receptor inhibitors were constructed with the successful development of sorafenib and regorafenib. This review focuses on those arylureas possessing anti-cancer activities from 2010 to date. According to their different mechanisms of action, these arylureas are divided into the following six categories: (1) Ras/Raf/MEK/ERK signaling pathway inhibitors; (2) tumor angiogenesis inhibitors, their targets include vascular endothelial growth factor receptors (VEGFRs), fibroblast growth factor receptors (FGFRs), platelet-derived growth factor receptors (PDGFRs), epidermal growth factor receptors (EGFRs), insulin-like growth factor 1 receptor (IGF-1R), Fms-like tyrosine kinase 3 (FLT3), c-Kit, MET, and Smoothened (Smo); (3) PI3K/AKT/mTOR signaling pathway inhibitors; (4) cell cycle inhibitors, their targets include checkpoint kinases (Chks), cyclin-dependent kinases (CDKs), Aurora, SUMO activating enzyme 1 (SUMO E1), tubulin, and DNA; (5) tumor differentiation, migration, and invasion inhibitors, their targets include matrix metalloproteinases (MMPs), LIM kinase (Limk), nicotinamide phosphoribosyltransferase (Nampt), and histone deacetylase (HDAC); (6) arylureas from the rational modification of natural products...
July 7, 2017: Current Topics in Medicinal Chemistry
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