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Sorafenib

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https://www.readbyqxmd.com/read/28342400/using-gene-expression-database-to-uncover-biology-functions-of-1-4-disubstituted-1-2-3-triazole-analogues-synthesized-via-a-copper-i-catalyzed-reaction
#1
Chun-Li Su, Chia-Ling Tseng, Chintakunta Ramesh, Hsiao-Sheng Liu, Chi-Ying F Huang, Ching-Fa Yao
We have synthesized bioactive 1,4-disubstituted 1,2,3-triazole analogues containing 2H-1,4-benzoxazin-3-(4H)-one derivatives via 1,3-dipolar cycloaddition in the presence of CuI. All the reactions proceeded smoothly and afforded its desired products in excellent yields. Among these analogues, 3y exhibited a better cytotoxic effect on human hepatocellular carcinoma (HCC) Hep 3B cells and displayed less cytotoxicity on normal human umbilical vein endothelial cells, compared with Sorafenib, a targeted therapy for advanced HCC...
March 18, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28339312/biomacromolecule-lipid-hybrid-nanoparticles-for-controlled-delivery-of-sorafenib-in-targeting-hepatocellular-carcinoma-therapy
#2
Jing Zhang, Tianqi Wang, Shengjun Mu, Livesey D Olerile, Xiaoyue Yu, Na Zhang
AIM: Hybrids composed of various materials are highly versatile for drug delivery in tumor therapy including hepatocellular carcinoma. Herein, a sorafenib (SF)-loaded biomacromolecule hyaluronic acid (HA)/lipid hybrid nanoparticles (HA/SF-cLNS) were developed for targeting drug delivery. MATERIALS & METHODS: In vitro assays determined HA/SF-cLNS release behavior, enzymatic degradation, uptake and cytotoxicity. H22-bearing liver cancer xenograft murine models were used to evaluate the biodistribution and therapeutic efficacy in vivo...
March 24, 2017: Nanomedicine
https://www.readbyqxmd.com/read/28339142/selective-effects-of-oral-anti-angiogenic-tyrosine-kinase-inhibitors-on-an-animal-model-of-hereditary-hemorrhagic-telangiectasia
#3
Yong Hwan Kim, Mi-Jung Kim, Se-Woon Choe, Dennis Sprecher, Young Jae Lee, S Paul Oh
BACKGROUND: Epistaxis and gastrointestinal (GI) tract hemorrhages are common symptoms of aged hereditary hemorrhagic telangiectasia (HHT) patients that result in anemia. Clinical as well as animal studies have suggested that vascular endothelial growth factor (VEGF) neutralizing antibodies lessen hemorrhage associated with adult onset arteriovenous malformations (AVMs). OBJECTIVES: The goal of this study is to evaluate potential therapeutic effects of oral delivery of four anti-angiogenic tyrosine-kinase inhibitors (TKIs) in the development of adult onset AVMs in a murine model of HHT...
March 24, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28338292/rational-drug-design-of-indazole-based-diarylurea-derivatives-as-anticancer-agents
#4
Yan-Yan Chu, He-Juan Cheng, Zhenhua Tian, Jian-Chun Zhao, Gang Li, Yang-Yang Chu, Chang-Jun Sun, Wen-Bao Li
A series of novel indazole-based diarylurea derivatives targeting c-kit were designed by structure-based drug design. The derivatives were prepared and their antiproliferative activities were evaluated against human colon cancer HCT-116 cell line and hepatocellular carcinoma PLC/PRF/5 cell line. The antiproliferative activities demonstrated that six out of nine compounds exhibited comparable activities with Sorafenib against HCT-116. The structure-activity relationship (SAR) analysis indicated that the indazole ring part tolerated different kinds of substituents, the N position of the central pyridine ring played key roles in antiproliferative activity...
March 24, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28335647/sorafenib-for-the-treatment-of-breast-cancer
#5
Giuseppe Bronte, Daniele Andreis, Sara Bravaccini, Roberta Maltoni, Lorenzo Cecconetto, Alessio Schirone, Alberto Farolfi, Anna Fedeli, Patrizia Serra, Caterina Donati, Dino Amadori, Andrea Rocca
Breast cancer treatment includes many options depending on the tumor clinicopathological profile, which groups breast cancer into various subtypes. Bevacizumab is currently the only drug capable of targeting angiogenesis in breast cancer. Sorafenib has also been studied in combination with other agents. Areas covered: Pharmacological aspects of sorafenib, including results from preclinical studies on breast cancer cells; findings about clinical efficacy and safety in both single-arm and randomized clinical trials; ongoing trials...
March 24, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28330784/vascular-endothelial-growth-factor-vegf-and-vegf-receptor-inhibitors-in-the-treatment-of-renal-cell-carcinomas
#6
REVIEW
Robert Roskoski
One Von Hippel-Lindau (VHL) tumor suppressor gene is lost in most renal cell carcinomas while the nondeleted allele exhibits hypermethylation-induced inactivation or inactivating somatic mutations. As a result of these genetic modifications, there is an increased production of VEGF-A and pro-angiogenic growth factors in this disorder. The important role of angiogenesis in the pathogenesis of renal cell carcinomas and other tumors has focused the attention of investigators on the biology of VEGFs and VEGFR1-3 and to the development of inhibitors of the intricate and multifaceted angiogenic pathways...
March 18, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28324324/prognostic-factors-of-sorafenib-therapy-in-hepatocellular-carcinoma-patients-with-failure-of-transarterial-chemoembolization
#7
Sangheun Lee, Jung Hyun Kang, Do Young Kim, Sang Hoon Ahn, Jun Yong Park, Beom Kyung Kim, Seung Up Kim, Kwang-Hyub Han
BACKGROUND: There is no approved therapy for patients with failed transarterial chemoembolization (TACE) and progression of hepatocellular carcinoma. We aimed to investigate the efficacy and prognostic factors in patients with TACE failure who received sorafenib rescue therapy. METHODS: We investigated 54 patients who met the criteria of TACE failure as defined by the international guidelines of Europe and Japan. Sorafenib was used as a rescue therapy. Overall survival (OS) and progression-free survival (PFS) were analyzed by Kaplan-Meier methods, and multivariate analysis was performed to find prognostic factors...
March 21, 2017: Hepatology International
https://www.readbyqxmd.com/read/28323861/overexpression-of-c-jun-contributes-to-sorafenib-resistance-in-human-hepatoma-cell-lines
#8
Yuki Haga, Tatsuo Kanda, Masato Nakamura, Shingo Nakamoto, Reina Sasaki, Koji Takahashi, Shuang Wu, Osamu Yokosuka
BACKGROUND: Despite recent advances in treatment strategies, it is still difficult to cure patients with hepatocellular carcinoma (HCC). Sorafenib is the only approved multiple kinase inhibitor for systemic chemotherapy in patients with advanced HCC. The majority of advanced HCC patients are resistant to sorafenib. The mechanisms of sorafenib resistance are still unknown. METHODS: The expression of molecules involved in the mitogen-activated protein kinase (MAPK) signaling pathway in human hepatoma cell lines was examined in the presence or absence of sorafenib...
2017: PloS One
https://www.readbyqxmd.com/read/28322221/venom-from-cuban-blue-scorpion-has-tumor-activating-effect-in-hepatocellular-carcinoma
#9
Catia Giovannini, Michele Baglioni, Marco Baron Toaldo, Matteo Cescon, Luigi Bolondi, Laura Gramantieri
Complementary and alternative medicine (CAM) is the term used to describe many kinds of products, practices, and systems that are not part of conventional medicine. Cancer patients usually do everything they can to combat the disease, manage its symptoms, and cope with the side effects of treatment. Unfortunately, patients who use CAM underestimate the risk of interaction with cancer therapy or worse they omit conventional therapy thus reducing the possibility of cancer remission. Herein we analyzed the effects of Vidatox 30 CH (venom extracted from the Junceus Rhopalurus scorpion) on hepatocellular carcinoma (HCC), the second leading cause of cancer-related deaths...
March 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28318881/targeted-therapy-in-thyroid-cancer-state-of-the-art
#10
L Valerio, L Pieruzzi, C Giani, L Agate, V Bottici, L Lorusso, V Cappagli, L Puleo, A Matrone, D Viola, C Romei, R Ciampi, E Molinaro, R Elisei
Thyroid cancer typically has a good outcome following standard treatments, which include surgery, radioactive iodine ablation for differentiated tumours and treatment with thyrotropine hormone-suppressive levothyroxine. Thyroid cancers that persist or recur following these therapies have a poorer prognosis. Cytotoxic chemotherapy or external beam radiotherapy has a low efficacy in these patients. 'Target therapy' with tyrosine kinase inhibitors (TKIs) represent an important therapeutic option for the treatment of advanced cases of radioiodine refractory (RAI-R) differentiated thyroid cancer (DTC), medullary thyroid cancer (MTC) and possibly for cases of poorly differentiated (PDTC) and anaplastic thyroid cancer (ATC)...
March 16, 2017: Clinical Oncology: a Journal of the Royal College of Radiologists
https://www.readbyqxmd.com/read/28318501/sorafenib-use-for-recurrent-hepatocellular-cancer-after-resection-or-transplantation-observations-from-a-us-regional-analysis-of-the-gideon-registry
#11
Robert C G Martin, Elizabeth Bruenderman, Allen Cohn, Bilal Piperdi, Rebecca Miksad, Jean-Francois Geschwind, Alec Goldenberg, Arun Sanyal, Ellen Zigmont, Svetlana Babajanyan, Pamela Foreman, Parvez Mantry, Brendan McGuire, Pierre Gholam
Treatment of unresectable recurrent hepatocellular carcinoma (HCC) in patients who recur after resection or orthotopic liver transplantation (OLT) remains a clinical challenge. One option is sorafenib, although little is known about its safety and tolerance in this unique patient population; therefore, we analyzed patients who underwent prior surgical resection and/or OLT and were treated with sorafenib in US cohort of GIDEON registry. In US, 645 patients were enrolled; 553 for intent to treat and 563 for safety...
November 18, 2016: American Journal of Surgery
https://www.readbyqxmd.com/read/28315488/sorafenib-as-a-potential-strategy-for-refractory-pulmonary-arterial-hypertension
#12
Gou Kimura, Masaharu Kataoka, Takumi Inami, Keiichi Fukuda, Hideaki Yoshino, Toru Satoh
Sorafenib is an inhibitor of multi-kinases including tyrosine and serine/threonine kinases. We investigated the efficacy and safety of sorafenib for the treatment of patients with refractory pulmonary arterial hypertension (PAH). Sorafenib was started in 9 patients (7 with idiopathic PAH, 2 with pulmonary veno-occlusive disease) who had severe PAH and right heart failure, in spite of treatment with vasodilators specific for PAH. Sorafenib was started as an add-on therapy at a dose of 50 or 100 mg/day, and increased to 100-400 mg/day...
March 14, 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28314990/an-apparent-clinical-pharmacokinetic-drug-drug-interaction-between-bevacizumab-and-the-anti-placental-growth-factor-monoclonal-antibody-ro5323441-via-a-target-trapping-mechanism
#13
Ka Wang, Franziska Schaedeli Stark, Tilman Schlothauer, Angelika Lahr, Valerie Cosson, Jianguo Zhi, Kai Habben, Jean Tessier, Eginhard Schick, Roland F Staack, Oliver Krieter
PURPOSE: RO5323441 is a humanized anti-placental growth factor (PlGF) monoclonal antibody that has shown preclinical activity in several cancer models. The objective of this analysis is to examine the pharmacokinetic (PK) results from four Phase I studies that have been conducted with RO5323441 (n = 61) and to report an apparent drug-drug interaction observed when RO5323441 was administered in combination with bevacizumab. METHODS: The four Phase I studies were a multiple-ascending dose study in 23 patients with solid tumors (Study 1), an open-label study in seven patients with colorectal/ovarian cancer (Study 2), a sorafenib combination study in nine patients with hepatocellular carcinoma (Study 3), and a bevacizumab combination study in 22 patients with recurrent glioblastoma (Study 4)...
April 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28304102/design-synthesis-and-cytotoxic-evaluation-of-certain-7-chloro-4-piperazin-1-yl-quinoline-derivatives-as-vegfr-ii-inhibitors
#14
Mohamed Nabil Aboul-Enein, Aida M Abd El-Sattar El-Azzouny, Fatma Abdel-Fattah Ragab, Mohamed Farouk Hamissa
Signaling pathway inhibition of VEGFR-II is visualized as valuable tool in cancer management. In the current study, the synthesis of novel 1-4-(7-chloroquinolin-4-yl)piperazin-1-yl)-2-(N-substituted-amino)-ethanone derivatives (4a-t) was achieved through the amination of 2-chloro-1-(4-(7-chloroquinolin-4-yl)piperazin-1-yl)ethanone (3) with different secondary amines. The structures of the target compounds were confirmed by IR, (1) H-NMR, (13) C-NMR, HRMS, and microanalysis. Compounds 4a-t were subjected to in vitro anticancer screening against human breast cancer (MCF-7) and prostate cancer (PC3) cell lines...
March 17, 2017: Archiv der Pharmazie
https://www.readbyqxmd.com/read/28302383/erratum-to-corrigendum-to-signal-transducer-and-activator-of-transcription-3-is-a-major-kinase-independent-target-of-sorafenib-in-hepatocellular-carcinoma
#15
Wei-Tien Tai, Ann-Lii Cheng, Chung-Wai Shiau, Hsiang-Po Huang, Jui-Wen Huang, Pei-Jer Chen, Kuen-Feng Chen
No abstract text is available yet for this article.
March 13, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28302001/liver-transplantation-for-hepatocellular-carcinoma-beyond-the-milan-criteria
#16
Fulya Gunsar
Hepatocellular carcinoma is the most common primary liver malignancy. Liver transplantation has been a successful therapy for selected patients with hepatocellular carcinoma. Since 1996, Milan criteria have been universally recognized as the guidelines for selecting patients with hepatocellular carcinoma for orthotopic liver transplantation. However, the simple use of tumor size and number has been insufficient to indicate the biologic features of hepatocellular carcinoma and to predict the risk of tumor recurrence...
March 2017: Experimental and Clinical Transplantation
https://www.readbyqxmd.com/read/28299645/new-concepts-in-embolotherapy-of-hcc
#17
REVIEW
F Pesapane, N Nezami, F Patella, J F Geschwind
Hepatocellular carcinoma (HCC) is the second most common cause of cancer-related deaths worldwide with rapidly growing incidence rates in the USA and Europe. Despite improving surveillance programs, most patients are diagnosed at intermediate to advanced stages and are no longer amenable to curative therapies, such as ablation, surgical resection and liver transplantation. For such patients, catheter-based image-guided embolotherapies such as transarterial chemoembolization (TACE) represent the standard of care and mainstay therapy, as recommended and endorsed by a variety of national guidelines and staging systems...
April 2017: Medical Oncology
https://www.readbyqxmd.com/read/28299600/sorafenib-a-review-in-hepatocellular-carcinoma
#18
REVIEW
Gillian M Keating
Sorafenib (Nexavar(®)) is currently the only systemic agent approved for use in hepatocellular carcinoma (HCC). Its approval was based on the results of the pivotal SHARP and Sorafenib Asia-Pacific (AP) trials in Child-Pugh (CP) class A patients with advanced HCC, which showed significantly longer median overall survival (OS) and time to radiological progression (TTP) with sorafenib 400 mg twice daily than with placebo, with no significant between-group difference in the median time to symptomatic progression (TTSP)...
March 15, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28298652/patient-specific-blood-pressure-correction-technique-for-arterial-stiffness-evaluation-in-a-cohort-on-anti-angiogenic-medication
#19
Bart Spronck, Tammo Delhaas, Anouk Gw De Lepper, Julie Giroux, François Goldwasser, Pierre Boutouyrie, Maureen Alivon, Koen D Reesink
Arterial pulse wave velocity (PWV) depends on blood pressure (BP). Correction of PWV for BP is commonly performed using a statistical approach, requiring a patient cohort. We recently developed a mechanistic, model-predictive approach to assess BP-independent changes in carotid PWV (cPWV) at the level of the individual. The goal of the present study is to compare our novel technique to conventional statistical correction, in the context of anti-cancer therapy using anti-angiogenic drugs (AADs). AADs frequently lead to a PWV increase, but also to hypertension, underlining the need for BP correction of PWV measurements...
March 16, 2017: Hypertension Research: Official Journal of the Japanese Society of Hypertension
https://www.readbyqxmd.com/read/28295594/the-albi-grade-predicts-the-prognosis-of-patients-with-advanced-hepatocellular-carcinoma-received-sorafenib
#20
Yuan-Hung Kuo, Jing-Houng Wang, Chao-Hung Hung, Kun-Ming Rau, I-Pei Wu, Chien-Hung Chen, Kwong-Ming Kee, Tsung-Hui Hu, Sheng-Nan Lu
BACKGROUND: The Albumin-Bilirubin (ALBI) grade is a new index to assess objectively liver function and prognosis in patients with hepatocellular carcinoma (HCC). This study aimed to elucidate the application of ALBI grade in baseline and sorafenib-end in advanced HCC patients received sorafenib. PATIENTS AND METHODS: A total of 415 consecutive advanced HCC patients in Child-Pugh A received sorafenib in our hospital. Sorafenib was terminated when radiologic tumor progression, or clinical liver function deterioration (LD) occurred in the reassessment bi-monthly...
March 11, 2017: Journal of Gastroenterology and Hepatology
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