keyword
MENU ▼
Read by QxMD icon Read
search

Vemurafenib

keyword
https://www.readbyqxmd.com/read/29782872/oxyfadichalcone-c-inhibits-melanoma-a375-cell-proliferation-and-metastasis-via-suppressing-pi3k-akt-and-mapk-erk-pathways
#1
Xiaolin Peng, Zhengming Wang, Yang Liu, Xin Peng, Yao Liu, Shan Zhu, Zhe Zhang, Yuling Qiu, Meihua Jin, Ran Wang, Qingying Zhang, Dexin Kong
AIMS: Melanoma remains to be one of the most incurable cancers. Discovery of novel antitumor agent for melanoma therapy is expected. We recently isolated Oxyfadichalcone C from Oxytropis falcate and investigated the anti-proliferative and anti-metastatic activity on human melanoma A375 cells in vitro. MAIN METHODS: Cell viability was determined using MTT assay and soft agar cloning formation assay. The effect of Oxyfadichalcone C on cell cycle distribution and apoptosis were analyzed by flow cytometry...
May 18, 2018: Life Sciences
https://www.readbyqxmd.com/read/29774135/vemurafenib-in-langerhans-cell-histiocytosis-report-of-a-pediatric-patient-and-review-of-the-literature
#2
Anne Heisig, Jan Sörensen, Stefanie-Yvonne Zimmermann, Stefan Schöning, Dirk Schwabe, Hans-Michael Kvasnicka, Raphaela Schwentner, Caroline Hutter, Thomas Lehrnbecher
Selective BRAF inhibitors such as vemurafenib have become a treatment option in patients with Langerhans cell Histiocytosis (LCH). To date, only 14 patients receiving vemurafenib for LCH have been reported. Although vemurafenib can stabilize the clinical condition of these patients, it does not seem to cure the patients, and it is unknown, when and how to stop vemurafenib treatment. We present a girl with severe multisystem LCH who responded only to vemurafenib. After 8 months of treatment, vemurafenib was tapered and replaced by prednisone and vinblastine, a strategy which has not been described to date...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29750749/vemurafenib-in-braf-mutant-metastatic-melanoma-patients-in-real-world-clinical-practice-prognostic-factors-associated-with-clinical-outcomes
#3
Maartje G Schouwenburg, Anouk Jochems, Brenda Leeneman, Margreet G Franken, Alfons J M van den Eertwegh, John B A G Haanen, Michiel C T van Zeijl, Maureen J Aarts, Alexander C J van Akkooi, Franchette W P J van den Berkmortel, Willeke A M Blokx, Jan Willem B de Groot, Geke A P Hospers, Ellen Kapiteijn, Rutger H Koornstra, Wim H Kruit, Marieke W J Louwman, Djura Piersma, Rozemarijn S van Rijn, Karijn P M Suijkerbuijk, Albert J Ten Tije, Gerard Vreugdenhil, Michel W J M Wouters, Jacobus J M van der Hoeven
The aim of this population-based study was to identify the factors associated with clinical outcomes in vemurafenib-treated patients and to evaluate outcomes across subgroups of patients with different risk profiles. Data were retrieved from the Dutch Melanoma Treatment Registry. Time to next treatment (TTNT) and overall survival (OS) of all metastatic melanoma patients who received vemurafenib between 2012 and 2015 were assessed using Kaplan-Meier estimates. A risk score was developed on the basis of all prognostic factors associated with TTNT and OS derived from multivariable Cox regression analyses...
May 10, 2018: Melanoma Research
https://www.readbyqxmd.com/read/29742076/update-on-hairy-cell-leukemia
#4
Robert J Kreitman, Evgeny Arons
Hairy cell leukemia (HCL) is a chronic B-cell malignancy with multiple treatment options, including several that are investigational. Patients present with pancytopenia and splenomegaly, owing to the infiltration of leukemic cells expressing CD22, CD25, CD20, CD103, tartrate-resistant acid phosphatase (TRAP), annexin A1 (ANXA1), and the BRAF V600E mutation. A variant lacking CD25, ANXA1, TRAP, and the BRAF V600E mutation, called HCLv, is more aggressive and is classified as a separate disease. A molecularly defined variant expressing unmutated immunoglobulin heavy variable 4-34 (IGHV4-34) is also aggressive, lacks the BRAF V600E mutation, and has a phenotype of HCL or HCLv...
March 2018: Clinical Advances in Hematology & Oncology: H&O
https://www.readbyqxmd.com/read/29737325/the-mek1-2-inhibitor-azd6244-sensitizes-braf-mutant-thyroid-cancer-to-vemurafenib
#5
Hao Song, Jinna Zhang, Liang Ning, Honglai Zhang, Dong Chen, Xuelong Jiao, Kejun Zhang
BACKGROUND [i]BRAF[/i]V600E mutation occurs in approximately 45% of papillary thyroid cancer (PTC) cases, and 25% of anaplastic thyroid cancer (ATC) cases. Vemurafenib/PLX4032, a selective BRAF inhibitor, suppresses extracellular signal-regulated kinase kinase/extracellular signal-regulated kinase 1/2 (MEK/ERK1/2) signaling and shows beneficial effects in patients with metastatic melanoma harboring the [i]BRAFV600E[/i] mutation. However, the response to vemurafenib is limited in BRAF-mutant thyroid cancer. The present study evaluated the effect of vemurafenib in combination with the selective MEK1/2 inhibitor AZD6244 on cell survival and explored the mechanism underlying the combined effect of vemurafenib and AZD6244 on thyroid cancer cells harboring BRAFV600E...
May 8, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29736211/therapeutic-effects-of-targeting-ras-erk-signaling-in-giant-congenital-melanocytic-nevi
#6
Qingxiong Yu, Min Wu, Lingling Sheng, Qingfeng Li, Feng Xie
Most giant congenital melanocytic nevi (GCMN) exhibit an activating mutation in NRAS. Constitutive activation of the RAS-ERK signaling pathway induces proliferation in nevus cells and plays a pivotal role in melanoma development. In this study, we studied the efficacy of RAS-ERK pathway targeted therapy in GCMN. We isolated nevus cells from GCMN (GNCs) and compared the morphology of GNCs with normal melanocytes and the A375 melanoma cell line. Proliferation curves of GNCs and A375 cells were determined using Cell Counting Kit-8 assays...
2018: American Journal of Translational Research
https://www.readbyqxmd.com/read/29727562/n-7-cyano-6-4-fluoro-3-3-trifluoromethyl-phenyl-acetyl-amino-phenoxy-1-3-benzothiazol-2-yl-cyclopropanecarboxamide-tak632-promotes-inhibition-of-braf-through-the-induction-of-inhibited-dimers
#7
Michael Grasso, Michelle A Estrada, Kiara N Berrios, Jeffrey D Winkler, Ronen Marmorstein
BRAFV600E is the most common activating mutation in melanoma and patients treated with BRAFV600E inhibitors all develop resistance within 1 year. A significant resistance pathway is paradoxical activation (transactivation) involving BRAF dimers, whereby an inhibitor bound protein subunit allosterically activates the other subunit. We recently reported on bivalent BRAFV600E -selective vemurafenib inhibitors that stabilize an inactive αC-out/αC-out homodimeric conformation with improved inhibitor potency and selectivity in vitro...
May 4, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29724167/vemurafenib-in-chinese-patients-with-braf-v600-mutation-positive-unresectable-or-metastatic-melanoma-an-open-label-multicenter-phase-i-study
#8
Lu Si, Xiaoshi Zhang, Zhen Xu, Qiudi Jiang, Lilian Bu, Xuan Wang, Lili Mao, Weijiang Zhang, Nicole Richie, Jun Guo
BACKGROUND: Melanoma is a rare, deadly disease without effective treatment options in China. Vemurafenib is a selective inhibitor of oncogenic BRAFV600 kinase approved in more than 90 countries, based on results obtained primarily in Caucasian patients. Limited data are available regarding the efficacy and safety of vemurafenib in Asian patients. METHODS: This phase I study investigated the pharmacokinetics, efficacy, and tolerability of vemurafenib (960 mg twice daily) in Chinese patients with BRAFV600 mutation-positive unresectable or metastatic melanoma...
May 3, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29721378/a-phase-ii-study-of-combined-therapy-with-a-braf-inhibitor-vemurafenib-and-interleukin-2-aldesleukin-in-patients-with-metastatic-melanoma
#9
Meghan J Mooradian, Alexandre Reuben, Peter A Prieto, Mehlika Hazar-Rethinam, Dennie T Frederick, Brandon Nadres, Adriano Piris, Vikram Juneja, Zachary A Cooper, Arlene H Sharpe, Ryan B Corcoran, Keith T Flaherty, Donald P Lawrence, Jennifer A Wargo, Ryan J Sullivan
Background : Approximately 50% of melanomas harbor BRAF mutations. Treatment with BRAF +/- MEK inhibition is associated with favorable changes in the tumor microenvironment thus providing the rationale for combining targeted agents with immunotherapy. Methods : Patients with unresectable Stage III or IV BRAFV600E mutant melanoma were enrolled in a single-center prospective study (n = 6). Patients were eligible to receive two courses of HD-IL-2 and vemurafenib twice daily. The primary endpoint was progression-free survival (PFS) with secondary objectives including overall survival (OS), response rates (RR), and safety of combination therapy as compared to historical controls...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29717260/a-modified-gene-trap-approach-for-improved-high-throughput-cancer-drug-discovery
#10
Shelli M Morris, Andrew J Mhyre, Savanna S Carmack, Carrie H Myers, Connor Burns, Wenjuan Ye, Marc Ferrer, James M Olson, Richard A Klinghoffer
While advances in laboratory automation has dramatically increased throughout of compound screening efforts, development of robust cell-based assays in relevant disease models remain resource-intensive and time-consuming, presenting a bottleneck to drug discovery campaigns. To address this issue, we present a modified gene trap approach to efficiently generate pathway-specific reporters that result in a robust "on" signal when the pathway of interest is inhibited. In this proof-of-concept study, we used vemurafenib and trametinib to identify traps that specifically detect inhibition of the mitogen-activated protein kinase (MAPK) pathway in a model of BRAFV600E driven human malignant melanoma...
May 2, 2018: Oncogene
https://www.readbyqxmd.com/read/29708404/braf-inhibition-with-concomitant-tumor-treating-fields-for-a-multiply-progressive-pleomorphic-xanthoastrocytoma
#11
Rimas V Lukas, Ryan T Merrell
Pleomorphic xanthoastrocytomas can be very resistant to treatment if they progress after standard therapy with surgery and radiation. We present the case of a patient with a multiply recurrent pleomorphic xanthoastrocytoma which demonstrated a sustained partial response to a combination regimen of the BRAF inhibitor vemurafenib and tumor treating fields. The regimen proved tolerable and efficacious in this case.
April 30, 2018: CNS Oncology
https://www.readbyqxmd.com/read/29702524/genetic-convergence-of-rare-lymphomas
#12
Jennifer R Shingleton, Sandeep S Dave
PURPOSE OF REVIEW: We review the genetic foundations of different rare lymphomas to examine their shared origins. These data indicate the potential application of genomics to improve the diagnosis and treatment of these rare diseases. RECENT FINDINGS: Next generation sequencing technologies have provided an important window into the genetic underpinnings of lymphomas. A growing body of evidence indicates that although some genetic alterations are specific to certain diseases, others are shared across different lymphomas...
April 26, 2018: Current Opinion in Hematology
https://www.readbyqxmd.com/read/29698368/targeted-inhibition-of-the-braf-pathway-in-a-patient-with-stage-iv-melanoma
#13
Breea Buckley, Bradley Pierce
This article describes the use of vemurafenib, a BRAF inhibitor, to achieve disease regression in a woman with extensive metastatic melanoma and the BRAF V600 gene mutation. Given the improved survival rates seen in these patients, clinicians need to be aware of long-term patient management and adverse reactions to the drug.
May 2018: JAAPA: Official Journal of the American Academy of Physician Assistants
https://www.readbyqxmd.com/read/29687639/modification-biological-evaluation-and-sar-studies-of-novel-1h-pyrazol-derivatives-containing-n-n-disubstituted-urea-moiety-as-potential-anti-melanoma-agents
#14
Ban-Feng Ruan, Meng-Xue Lin, Qin Shao, Tian-Hong Wang, Qing Zhang, Yu-Lu Dong, Chao-Nan Bu, Hua-Jian Xu, Ben-Guo Zhou, Qing-Shan Li
Malignant melanoma is one of the most aggressive cancer. BRAF inhibitors have exhibited therapeutic effects against BRAF-mutant melanoma. In continuation of our earlier studies on 1H-pyrazole skeleton based anti-melanoma agent, two sets of novel compounds that include 1H-pyrazole-4-amines FA1-13 and corresponding urea derivatives FN1-13 have been synthesized and evaluated for their BRAFV 600E inhibitory and anti-proliferation activities. Compound FN10 displayed the most potent biological activity against BRAFV 600E (IC50 = 0...
April 23, 2018: Chemistry & Biodiversity
https://www.readbyqxmd.com/read/29685423/response-to-the-therapy-in-hairy-cell-leukemia-systematic-review-and-meta-analysis
#15
REVIEW
Iga Andrasiak, Justyna Rybka, Tomasz Wrobel
Hairy cell leukemia is an uncommon chronic B-cell lymphoproliferative disorder. Various treatment options are available. The objective of the study was to evaluate through meta-analysis the pooled proportions of patients responding to each therapeutic agent. We conducted a systematic review and meta-analysis to estimate the pooled response rate to modern hairy cell leukemia therapies. Articles published between January 1992 and August 2017 were identified by searching PubMed, Web of Science, and the Cochrane Library...
March 31, 2018: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29684045/autophagic-flux-blockage-by-accumulation-of-weakly-basic-tenovins-leads-to-elimination-of-b-raf-mutant-tumour-cells-that-survive-vemurafenib
#16
Marcus J G W Ladds, Andrés Pastor-Fernández, Gergana Popova, Ingeborg M M van Leeuwen, Kai Er Eng, Catherine J Drummond, Lars Johansson, Richard Svensson, Nicholas J Westwood, Anna R McCarthy, Fredrik Tholander, Mihaela Popa, David P Lane, Emmet McCormack, Gerald M McInerney, Ravi Bhatia, Sonia Laín
Tenovin-6 is the most studied member of a family of small molecules with antitumour activity in vivo. Previously, it has been determined that part of the effects of tenovin-6 associate with its ability to inhibit SirT1 and activate p53. However, tenovin-6 has also been shown to modulate autophagic flux. Here we show that blockage of autophagic flux occurs in a variety of cell lines in response to certain tenovins, that autophagy blockage occurs regardless of the effect of tenovins on SirT1 or p53, and that this blockage is dependent on the aliphatic tertiary amine side chain of these molecules...
2018: PloS One
https://www.readbyqxmd.com/read/29682188/imaging-markers-of-response-to-combined-braf-and-mek-inhibition-in-braf-mutated-vemurafenib-sensitive-and-resistant-melanomas
#17
Stefania Acciardo, Lionel Mignion, Nicolas Joudiou, Caroline Bouzin, Jean-François Baurain, Bernard Gallez, Bénédicte F Jordan
A majority of patients with a V600x melanoma respond quickly to BRAF/MEK inhibition (BRAFi/MEKi) and have an obvious clinical benefit. Nearly all the patients after this initial phase will develop resistance. Therefore, non-invasive early markers of response/non-response are needed in order to identify those patients who, due to intrinsic or acquired resistance, do not respond to treatment and would be eligible for alternative treatments. The aim of this study was to investigate the value of magnetic resonance spectroscopy (1 H-MRS) of choline and diffusion-weighted magnetic resonance imaging (DW-MRI) as early markers of response to BRAF inhibition (BRAFi) with vemurafenib alone or in combination with MEK inhibition (MEKi) with trametinib, in BRAFi-sensitive and BRAFi-resistant melanoma xenografts...
March 30, 2018: Oncotarget
https://www.readbyqxmd.com/read/29674508/combined-braf-and-hsp90-inhibition-in-patients-with-unresectable-braf-v600e-mutant-melanoma
#18
Zeynep Eroglu, Yian Ann Chen, Geoffrey T Gibney, Jeffrey S Weber, Ragini R Kudchadkar, Nikhil I Khushalani, Joseph Markowitz, Andrew S Brohl, Leticia F Tetteh, Howida Ramadan, Gina Arnone, Jiannong Li, Xiuhua Zhao, Ritin Sharma, Lancia N F Darville, Bin Fang, Inna Smalley, Jane L Messina, John M Koomen, Vernon K Sondak, Keiran S M Smalley
PURPOSE: BRAF inhibitors are clinically active in patients with advanced BRAFV600 -mutant melanoma, although acquired resistance remains common. Preclinical studies demonstrated that resistance could be overcome using concurrent treatment with the HSP90 inhibitor XL888. METHODS: Vemurafenib (960 mg PO BID) combined with escalating doses of XL888 (30, 45, 90 or 135 mg PO twice weekly) was investigated in 21 patients with advanced BRAFV600 -mutant melanoma. Primary endpoints were safety and determination of a maximum tolerated dose...
April 19, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29662661/targeting-oncogenic-ras-by-the-clostridium-perfringens-toxin-tpel
#19
Björn Schorch, Hannah Heni, Nour-Imene Zahaf, Tilman Brummer, Marina Mione, Gudula Schmidt, Panagiotis Papatheodorou, Klaus Aktories
Clostridium perfringens toxin TpeL belongs to the family of large clostridial glycosylating toxins. The toxin causes N-acetylglucosaminylation of Ras proteins at threonine35 thereby inactivating the small GTPases. Here, we show that all main types of oncogenic Ras proteins (H-Ras, K-Ras and N-Ras) are modified by the toxin in vitro and in vivo . Toxin-catalyzed modification of Ras was accompanied by inhibition of the MAP kinase pathway. Importantly, TpeL inhibited the paradoxical activation of the MAP kinase pathway induced by the BRAF inhibitor Vemurafenib in the human melanoma cell line SBCL2...
March 27, 2018: Oncotarget
https://www.readbyqxmd.com/read/29645280/effect-of-vemurafenib-on-the-pharmacokinetics-of-a-single-dose-of-digoxin-in-patients-with-braf-v600-mutation-positive-metastatic-malignancy
#20
Weijiang Zhang, Christine McIntyre, Melissa Kuhn, Harper Forbes, Tae Min Kim, Jeeyun Lee, Lev Demidov, Dawn Colburn
The primary objective of this phase 1, open-label, multicenter, 3-period, fixed-sequence study was to evaluate the effect of multiple doses of vemurafenib on the pharmacokinetics of a single dose of digoxin, a probe P-glycoprotein (P-gp) substrate, in patients with BRAFV600 mutation-positive metastatic malignancy. Following a 28-day screening period, patients received a single oral dose of digoxin 0.25 mg on day 1 in period A, oral vemurafenib 960 mg twice daily for 21 days in period B (days 8-28), and a single oral dose of digoxin 0...
April 12, 2018: Journal of Clinical Pharmacology
keyword
keyword
10323
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"