Search results for "Neoplastic"
showing 10 items of 2901 documents
Development and validation of a micellar liquid chromatographic method to determine three antitumorals in plasma
2017
Aim: A micellar liquid chromatographic method to determine several anticancer drugs (pazopanib, dabrafenib and regorafenib) in plasma was developed and validated by the guidelines of the EMA. Experimental: Plasma samples were directly injected, after a 1/5-dilution in a micellar solution. The drugs were resolved in <18 min using a C18 column. The mobile phase was an aqueous solution of 0.12 M SDS – 2% 1-pentanol, buffered at pH 7. The detection was performed by absorbance at 260 nm. Results: The values of the main validation parameters were: LOD (0.1–1 mg/l), calibration range (0.2–2 to 80 mg/l), accuracy (-12.5 to +11.7%) and precision (<11.9%). Conclusion: The procedure was conduct…
Therapeutic implications of Cancer Initiating Cells.
2009
Background: Until few years ago, all neoplastic cells within a tumour were suggested to have tumorigenic capacity, but recent evidences hint to the possibility that such feature is confined to a subset of Cancer Initiating Cells (CICs), also called Cancer Stem Cells (CSCs). These cells are the reservoir of the heterogeneous populations of differentiated cancer cells constituting the tumour bulk. Mechanisms shared with somatic stem cells, such as quiescence, self-renewal ability, asymmetric division and multidrug resistance, allow to these cells to drive tumour growth and to evade conventional therapy. Objective: Here, we give a brief overview on the origin of CICs, the mechanisms involved i…
Natural Products Derived from Traditional Chinese Medicine as Novel Inhibitors of the Epidermal Growth Factor Receptor
2010
The epidermal growth factor receptor (EGFR) has become an important molecular target in cancer therapy. Various small molecules and therapeutic antibodies targeting EGFR family members have been developed during recent years and are established in clinical oncology. However, increasing clinical application of EGFR tyrosine kinase inhibitors has resulted in the development of resistance to EGFR-targeting drugs due to the selection of EGFR-mutated variants. This phenomenon forced the search for novel EGFR inhibitors with activity towards EGFR-mutant tumors. This review describes recent achievements in natural products derived from medicinal plants as novel EGFR inhibitors.
Finding the right dose of fulvestrant in breast cancer
2012
Fulvestrant is a selective estrogen receptor downregulator, behaving as a complete antagonist. It was initially approved, at a dose of 250 mg, to treat hormone dependant breast cancer in second line setting. However, a series of pharmacological and pre-clinical studies have suggested that a higher dose of 500 mg may be more effective. The present work summarizes and discusses clinical trials that have aimed to test the benefits of administering fulvestrant at a higher dose. The data support the use of a higher, and more possibly, effective dose of the agent.
A preclinical model for skin sensitization prediction of antineoplasic drugs.
2020
e15643 Background: Skin side effects are common manifestations of antineoplastic drugs that are frequently observed in early clinical trials. Therefore, there is a need to identify skin toxic agents before clinical development in order to predict severe skin manifestations. In many cases, skin toxicity is due to sensitization, a key immunologic process mediating redness, swelling and itching that can lead to more severe skin alterations. Methods: We adapted three skin cellular in vitro techniques for cutaneous drug sensitization assessment of the Organization for Economic Cooperation and Development (OECD, 2012) in order to predict antineoplastic drug skin sensitization: 1) Direct peptide …
Collagen-induced differential expression of an RNA polymerase subunit by breast cancer cells
2005
It was previously reported that the stroma of ductal infiltrating carcinoma (DIC) of the human breast contains considerable amount of an embryo-foetal collagen type, OF/LB (onco-foetal/laminin-binding), and that adhesion of 8701-BC DIC cells onto OF/LB collagen substrates selectively promotes cell growth, motility, production of extracellular lytic enzymes and invasion "in vitro" if compared with other collagen species. To detect possible transcriptional differences for regulatory proteins following OF/LB collagen-cell interactions, we submitted RNA preparations from 8701-BC cells grown on collagen type I, IV and OF/LB to "differential display"-PCR in the presence of degenerate C(2)H(2) zin…
2-Cinnamamido, 2-(3-phenylpropiolamido), and 2-(3-phenylpropanamido)benzamides: synthesis, antiproliferative activity, and mechanism of action
2013
Abstract Several new benzamides 4a–q were synthesized by stirring in pyridine the acid chlorides 3a–q with the appropriate anthranilamide derivatives 2a–g. Some of the synthesized compounds were evaluated for their in vitro antiproliferative activity against a panel of 5 human cell lines (K562 human chronic myelogenous leukemia cells, MCF-7 breast cancer cells, HTC-116 and HT26 colon cancer cells and NCI H460 non-small cell lung cancer cells).
Proliferation state and polo-like kinase1 dependence of tumorigenic colon cancer cells.
2012
Abstract Tumor-initiating cells are responsible for tumor maintenance and relapse in solid and hematologic cancers. Although tumor-initiating cells were initially believed to be mainly quiescent, rapidly proliferating tumorigenic cells were found in breast cancer. In colon cancer, the proliferative activity of the tumorigenic population has not been defined, although it represents an essential parameter for the development of more effective therapeutic strategies. Here, we show that tumorigenic colon cancer cells can be found in a rapidly proliferating state in vitro and in vivo, both in human tumors and mouse xenografts. Inhibitors of polo-like kinase1 (Plk1), a mitotic kinase essential fo…
Dynamic regulation of the cancer stem cell compartment by Cripto-1 in colorectal cancer.
2015
Stemness was recently depicted as a dynamic condition in normal and tumor cells. We found that the embryonic protein Cripto-1 (CR1) was expressed by normal stem cells at the bottom of colonic crypts and by cancer stem cells (CSCs) in colorectal tumor tissues. CR1-positive populations isolated from patient-derived tumor spheroids exhibited increased clonogenic capacity and expression of stem-cell-related genes. CR1 expression in tumor spheroids was variable over time, being subject to a complex regulation of the intracellular, surface and secreted protein, which was related to changes of the clonogenic capacity at the population level. CR1 silencing induced CSC growth arrest in vitro with a …
Evaluation of ABC gene polymorphisms on the pharmacokinetics and pharmacodynamics of capecitabine in colorectal patients: Implications for dosing rec…
2020
Aims The aims are to develop a population pharmacokinetic model of capecitabine (CAP) and its main metabolites after the oral administration of CAP in colorectal cancer patients with different polymorphisms of the ATP-binding cassette (ABC) gene and a population pharmacokinetic/pharmacodynamic model capable of accounting for the neutropenic effects, and to optimize the dosing strategy based on the polymorphisms of the ABC gene and/or the administration regimen as a single agent or in combination. Methods Forty-eight patients diagnosed with colorectal cancer were included, with 432 plasma levels of CAP, 5'-desoxi-5-fluorouridine (5'-DFUR) and 5-fluorouracil (5-FU), and 370 neutrophil observa…