Search results for "Indole"
showing 10 items of 570 documents
A multicenter DeCOG study on predictors of vemurafenib therapy outcome in melanoma: pretreatment impacts survival
2015
Background: Kinase inhibitors targeting the BRAF V600 mutation have become standard in the treatment of metastatic melanoma. Albeit in wide clinical use, the patterns associated with therapy outcome are not fully elucidated. The present study was aimed to identify predictive factors of therapy response and survival under the BRAF inhibitor vemurafenib. Patients and methods: This multicenter retrospective study analyzed patient, tumor, and pretreatment characteristics collected in BRAF V600-mutated stage IV melanoma patients before single-agent therapy with the BRAF inhibitor vemurafenib. Results: A total of 300 patients from 14 centers were included into this study with a median follow-up t…
Efficacy and safety of regorafenib for advanced gastrointestinal stromal tumours after failure of imatinib and sunitinib (GRID): an international, mu…
2013
Contains fulltext : 118365.pdf (Publisher’s version ) (Closed access) BACKGROUND: Until now, only imatinib and sunitinib have proven clinical benefit in patients with gastrointestinal stromal tumours (GIST), but almost all metastatic GIST eventually develop resistance to these agents, resulting in fatal disease progression. We aimed to assess efficacy and safety of regorafenib in patients with metastatic or unresectable GIST progressing after failure of at least imatinib and sunitinib. METHODS: We did this phase 3 trial at 57 hospitals in 17 countries. Patients with histologically confirmed, metastatic or unresectable GIST, with failure of at least previous imatinib and sunitinib were rando…
Rituximab for indolent lymphomas before and after allogeneic hematopoietic stem cell transplantation
2015
Purpose of review The most substantial advancement in the treatment of indolent B-cell non-Hodgkin lymphoma (NHL), since the advent of combination chemotherapy, has been the introduction of the monoclonal anti-CD20 antibody rituximab. However, the optimal schedule, timing, and duration of rituximab therapy remain controversial. Recent findings Since its initially reported single-agent activity in 1997, the role of rituximab has greatly expanded and it is now ubiquitously integrated in all treatment phases of indolent NHL. Yet, several questions remain to be addressed: should asymptomatic patients be treated at diagnosis with single-agent rituximab or still kept in watchful waiting, what are…
Transplantation in follicular lymphoma: not "yes or no" but "whom and when".
2013
After years of debate, the question as to what is the optimal use of transplantation strategies in indolent lymphoma remains controversial. In the July issue of Haematologica, a study was published by the EBMT Lymphoma Working Party that aims to define indications for hematopoietic stem cell
Single Heteroatom Fine-Tuning of the Emissive Properties in Organoboron Complexes with 7-(Azaheteroaryl)indole Systems
2016
The application of organoboron compounds as light-absorbing or light-emitting species in areas as relevant as organic electronics or biomedicine has motivated the search for new materials which contribute to the progress of those applications. This article reports the synthesis of four-coordinate boron complexes based on the unexplored 7-(azaheteroaryl)indole ligands. An easy synthetic approach has enabled the fine-tuning of the electronic structure of the organoboron species by modifying a heteroaromatic component in the conjugated system. Furthermore, a comprehensive characterization by X-ray diffraction, absorption and emission spectroscopy, both in solution and in the solid state, cycli…
MCC1019, a selective inhibitor of the Polo-box domain of Polo-like kinase 1 as novel, potent anticancer candidate
2019
Polo-like kinase (PLK1) has been identified as a potential target for cancer treatment. Although a number of small molecules have been investigated as PLK1 inhibitors, many of which showed limited selectivity. PLK1 harbors a regulatory domain, the Polo box domain (PBD), which has a key regulatory function for kinase activity and substrate recognition. We report on 3-bromomethyl-benzofuran-2-carboxylic acid ethyl ester (designated: MCC1019) as selective PLK1 inhibitor targeting PLK1 PBD. Cytotoxicity and fluorescence polarization-based screening were applied to a library of 1162 drug-like compounds to identify potential inhibitors of PLK1 PBD. The activity of compound MC1019 against the PLK1…
Discovery of the 3-Amino-1,2,4-triazine-Based Library as Selective PDK1 Inhibitors with Therapeutic Potential in Highly Aggressive Pancreatic Ductal …
2023
Pyruvate dehydrogenase kinases (PDKs) are serine/threonine kinases, that are directly involved in altered cancer cell metabolism, resulting in cancer aggressiveness and resistance. Dichloroacetic acid (DCA) is the first PDK inhibitor that has entered phase II clinical; however, several side effects associated with weak anticancer activity and excessive drug dose (100 mg/kg) have led to its limitation in clinical application. Building upon a molecular hybridization approach, a small library of 3-amino-1,2,4-triazine derivatives has been designed, synthesized, and characterized for their PDK inhibitory activity using in silico, in vitro, and in vivo assays. Biochemical screenings showed that …
Insights into the Maya Blue technology: greenish pellets from the ancient city of La Blanca.
2011
Financial support is gratefully acknowledged from the MEC Projects CTQ2011-28079-CO3-01 and 02 which are also supported with ERDF funds. Research was conducted within the "Grupo de anlisis cientifico de bienes culturales y patrimoniales y estudios de ciencia de la conservacion" Microcluster of the University of Valencia Excellence Campus. The authors would like to thank Dr. Isabel Solana (SCSIE, UV), Dr. Jose Luis Moya Lopez, and Manuel Planes Insausti (Microscopy Service UPV) for their technical support.
Preservation of glial cytoarchitecture from ex vivo human tumor and non-tumor cerebral cortical explants: A human model to study neurological diseases
2007
For the human brain, in vitro models that accurately represent what occurs in vivo are lacking. Organotypic models may be the closest parallel to human brain tissue outside of a live patient. However, this model has been limited primarily to rodent-derived tissue. We present an organotypic model to maintain intraoperatively collected human tumor and non-tumor explants ex vivo for a prolonged period of time (similar to 11 days) without any significant changes to the tissue cytoarchitecture as evidenced through immunohistochemistry and electron microscopy analyses. The ability to establish and reliably predict the cytoarchitectural changes that occur with time in an organotypic model of tumor…
Development of [1,2]oxazoloisoindoles tubulin polymerization inhibitors: Further chemical modifications and potential therapeutic effects against lym…
2022
Lymphomas are among the ten most common cancers, and, although progress has been achieved in increasing survival, there is still an unmet need for more effective therapeutic approaches, including better options for patients with refractory tumors that initially respond but then relapse. The lack of effective alternative treatment options highlights the need to develop new therapeutic strategies capable of improving survival prospects for lymphoma patients. Herein, we describe the identification and exploration of the SAR of a series of [1,2]oxazolo[5,4-e]isoindoles as potent small molecules that bind to the colchicine site of tubulin and that have promise for the treatment of refractory lym…