Abstract:
:Lipophilic derivatives of the anticancer drug paclitaxel (PTX) were prepared by means of its conjugation to lipoamino acid (LAA) residues, with the aim of increasing drug accumulation in tumor cells. PTX was linked to the methyl esters of norleucine (C6) or 2-aminodecanoic acid (C10). A succinic acid group was used as a spacer to link the 2'-hydroxyl group of PTX and the LAA residue, respectively by means of an ester and an amide bond. The in vitro anticancer activity of the prodrugs was tested on a human thyroid anaplastic cancer cell line (ARO). The intracellular uptake kinetics of free PTX and its prodrugs was assessed by HPLC. PTX-LAA prodrugs showed a noticeable cytotoxic activity against ARO cells at shorter incubation time (12 h) and lower doses (0.01-0.1 microM) than PTX. Intracellular accumulation experiments indicated an improvement of drug concentration inside these cells, related to the block of the cellular expulsion by means of multi drug resistance efflux complex and improved physicochemical features that allowed the greater passive cellular membrane permeation. The enhanced activity of PTX-LAA prodrugs, in terms of potency and onset of the effect, as well as the interesting intracellular accumulation data suggest that these compounds can be further tested as possible alternatives to PTX for the treatment of resistant cancer cells.
journal_name
Curr Cancer Drug Targetsjournal_title
Current cancer drug targetsauthors
Pignatello R,Paolino D,Pantò V,Pistară V,Calvagno MG,Russo D,Puglisi G,Fresta Mdoi
10.2174/156800909787580944subject
Has Abstractpub_date
2009-03-01 00:00:00pages
202-13issue
2eissn
1568-0096issn
1873-5576journal_volume
9pub_type
杂志文章abstract::Preferentially expressed antigen in melanoma (PRAME) is the best characterized member of the PRAME family of leucine-rich repeat (LRR) proteins. Mammalian genomes contain multiple members of the PRAME family whereas in other vertebrate genomes only one PRAME-like LRR protein was identified. PRAME is a cancer/testis an...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009616666151222151818
更新日期:2016-01-01 00:00:00
abstract::Wild-type Wilms' tumor gene WT1 is expressed at high levels not only in most of acute myelocytic, acute lymphocytic, and chronic myelocytic leukemia, but also in various types of solid tumors including lung cancer. We tested the ability of the gene product (WT1) to serve as a target antigen for tumor specific immunot...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009023334088
更新日期:2002-03-01 00:00:00
abstract::The integrin family of cell surface receptors integrates cell-extracellular matrix interactions with the cell cytoskeleton and signalling across the cell membrane, resulting in an important role in cell adhesion, mobility and migration, proliferation, and survival. Changes in the number and identity of integrin recept...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800909788486713
更新日期:2009-06-01 00:00:00
abstract:BACKGROUND:Osteosarcoma is an aggressive bone tumor. Itrepresents the principal cause of cancer-associated death in children.Considering the recent findings on the role of iron in cancer, iron chelation has been investigated for its antineoplastic properties in many tumors. Deferasirox is the most used iron chelator co...
journal_title:Current cancer drug targets
pub_type: 杂志文章
doi:10.2174/1568009620666201230090531
更新日期:2020-12-29 00:00:00
abstract::Scaffold-based analogs of cinnamic acid benzyl amide (CABA) exhibit pleiotropic effects in cancer cells, and their exact molecular mechanism of action is under investigation. The present study is part of our systemic analysis of interactions of CABA analogs with their molecular targets. These compounds were shown to i...
journal_title:Current cancer drug targets
pub_type: 杂志文章
doi:10.2174/1568009614666140821122718
更新日期:2014-01-01 00:00:00
abstract::Gastrointestinal (GI) tumors are among the leading cause of death in cancer patients worldwide. Particularly, gastric cancer (GC) is the third cause of cancer deaths, whereas esophageal neoplasm is the eighth leading most common cancer worldwide and its incidence, especially adenocarcinoma type, is continuously increa...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009617666170208162058
更新日期:2018-01-01 00:00:00
abstract::Membranous Met is classically identified with its role in cancer metastases, while nuclear Met is associated with a more invasive, aggressive and proliferative form of cancer. Full-length Met or N-terminal transmembrane domain cleaved Met can translocate into nucleus in a cell growth and pH dependent but both ligand-d...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009616666160105105250
更新日期:2016-01-01 00:00:00
abstract::Cyclooxygenase-2 (COX-2) is a critical enzyme implicated in chronic inflammation-associated cancer development. Our studies have shown that the exposure of Beas-2B cells, a human bronchial epithelial cell line, to lung carcinogenic nickel compounds results in increased COX-2 expression. However, the signaling pathways...
journal_title:Current cancer drug targets
pub_type: 杂志文章
doi:10.2174/156800911795656001
更新日期:2011-06-01 00:00:00
abstract::Copper is a trace element which is tightly regulated in mammals and lower animals. Disruptions of copper homeostasis in humans are rare and they cause serious disorders such as Wilson's disease and Menke's disease. Copper plays an important role in promoting physiological and malignant angiogenesis. Formation of new b...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800905774574066
更新日期:2005-11-01 00:00:00
abstract::As microtubules are essential in many cell functions, they have been used as a target of a variety of anticancer drugs that are grouped as stabilizing (taxanes) and destabilizing (vinca-alkaloids, colchicinoids) microtubule agents. It appears clearly now that the dynamic behaviour more than modifications of microtubul...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800907783220426
更新日期:2007-12-01 00:00:00
abstract::Breast cancer is one of the most prevalent and devastating malignant diseases in women worldwide. Fortunately, while breast cancer incidence is still increasing, its death rate is declining. This is mainly due to early diagnosis and potent therapies such as blockade of estrogen receptor- or of ErbB2 (HER2-neu) membran...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009611313020008
更新日期:2013-02-01 00:00:00
abstract::The application of nanotechnology to biomedical research is expected to have a major impact leading to the development of new types of diagnostic and therapeutic tools. One focus in nanobiotechnology is to develop safe and efficient drug/gene delivery vehicles. Research into the rational delivery and targeting of phar...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800911794328411
更新日期:2011-02-01 00:00:00
abstract::In this early phase of the new era of molecularly targeted patient friendly cancer chemotherapy, there is a need for novel viable anticancer molecular targets. The MDM2 oncoprotein has been validated as a potential target for cancer drug development. MDM2 amplification and/or overexpression occur in a wide variety of ...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009053332672
更新日期:2005-02-01 00:00:00
abstract::The total expression profiles of two medulloblastoma cell lines resistant to the preactivated form of cyclophosphamide (4-hydroperoxycyclophosphamide, 4-HC) were examined using the Affymetrix GeneChip U133A array. Our primary objective was to look for possible genes, other than the well-studied aldehyde dehydrogenases...
journal_title:Current cancer drug targets
pub_type: 杂志文章
doi:10.2174/156800908784293631
更新日期:2008-05-01 00:00:00
abstract::Polyisoprenylated proteins (PPs) methylation by polyisoprenylated protein methyl transferase (PPMTase) is counteracted by polyisoprenylated methylated protein methyl esterase (PMPMEase). This is the only reversible step of the polyisoprenylation pathway as the relative amounts of the acid and ester forms are determine...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800910791859443
更新日期:2010-09-01 00:00:00
abstract::Constitutive activation of the EGFR/RAS/PI3K cell-signaling pathway that may occur through molecular aberrations in core pathway components occurs in many solid tumours, including colorectal cancer(CRC), non-small-cell lung cancer(NSCLC) and breast cancer. Predictive biomarkers of response to therapeutics targeting th...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800910793357925
更新日期:2010-12-01 00:00:00
abstract:BACKGROUND AND AIM:Translational data suggest that nucleoside transporters, in particular human equilibrative nucleoside transporter 1 (hENT1), play an important role in predicting clinical outcome after gemcitabine chemotherapy for several types of cancer. The aim of this study was to retrospectively determine patient...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800911793743600
更新日期:2011-01-01 00:00:00
abstract::Heat shock proteins (HSPs) are molecular chaperones that stabilize folding and conformation of normal as well as oncogenic proteins. These chaperones thereby prevent the formation of protein aggregates. HSPs are often overexpressed in human malignancies, including AML. HSP90 is the main chaperon required for the stabi...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800909789271486
更新日期:2009-09-01 00:00:00
abstract::The anticancer properties of histone deacetylase inhibitors have been known for some time. However, it is only recently that the functional identities of the intracellular targets mediating the anticancer properties have started to be revealed. These targets appear to play significant roles in cell cycle control, apop...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009023333818
更新日期:2002-12-01 00:00:00
abstract::Drugs that target the vascular endothelial growth factor (VEGF) and platelet derived growth factor (PDGF) pathways have revolutionized the treatment of patients with metastatic renal cell cancer (RCC). Patients with clear cell RCC often have mutations or silencing of the von Hippel Lindau gene leading to an accumulati...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800908786733450
更新日期:2008-12-01 00:00:00
abstract::Cancer drug therapy is undergoing a major transition from the previous pregenomic cytotoxic era to the new postgenomic era. Future mechanism-based therapeutic agents will increasingly be designed to act on molecular targets that are causally involved in the malignant progression of human cancers. Such agents are predi...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009013334269
更新日期:2001-05-01 00:00:00
abstract::Therapeutic vaccines continue to be one of the most active fields in cancer research. However, despite clear evidence of antitumor effect in laboratory animals, and despite the ability of current vaccine candidates to elicit tumor specific antibodies and T-cells in humans, objective responses in the clinical trials ar...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800911793743583
更新日期:2011-01-01 00:00:00
abstract::(5Z,9Z)-11-Phenylundeca-5,9-dienoic acid was stereoselectively synthesized, based on original cross-cyclomagnesiation of 2-(hepta-5,6-dien-1-yloxy)tetrahydro-2H-pyran and buta-2,3-dien-1-ylbenzene with EtMgBr in the presence of the Cp2TiCl2 catalyst giving 2,5-dialkylydenemagnesacyclopentane in 86% yield. The acid hyd...
journal_title:Current cancer drug targets
pub_type: 杂志文章
doi:10.2174/1568009615666150506093155
更新日期:2015-01-01 00:00:00
abstract::Histone deacetylase inhibitors (HDACi) belong to a novel class of drugs able to act on the epigenome, indirectly remodeling the spatial conformation of the chromatin: by increasing histone acetylation these drugs ultimately promote the detachment of the DNA from the nucleosome octamer, therefore allowing the access of...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800908784533508
更新日期:2008-06-01 00:00:00
abstract::The actin microfilament network is important in maintaining cell shape and function in eukaryotic cells. It has a multitude of roles in cellular processes such as cell adhesion, motility, cellular signalling, intracellular trafficking and cytokinesis. Alterations in the organisation of the cytoskeleton and changes in ...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800906776842948
更新日期:2006-05-01 00:00:00
abstract:BACKGROUND:Oncolytic viruses (OVs), which preferentially infect cancer cells and induce host anti-tumor immune responses, have emerged as an effective melanoma therapy. Tanapoxvirus (TANV), which possesses a large genome and causes mild self-limiting disease in humans, is potentially an ideal OV candidate. Interleukin-...
journal_title:Current cancer drug targets
pub_type: 杂志文章
doi:10.2174/1568009617666170630143931
更新日期:2018-01-01 00:00:00
abstract::One of the older and most validated cancer treatments is endocrine therapy. Some tumors are dependent on hormone stimulation for growth, and therefore therapeutic interventions aiming to deprive the cells of the hormone are feasible and have been successful. Tumor growth also depends in some cases on growth factors, s...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800907780618310
更新日期:2007-05-01 00:00:00
abstract::The efficacy of cancer immunotherapy relies on the ability of the host immune system to recognise the cancer as non-self and eliminate it from the body. Whilst this is an extremely fertile area of medical research, with positive clinical trials showing durable responses, attention must be paid to the subset of patient...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009617666170206105131
更新日期:2018-01-01 00:00:00
abstract::Prostate cancer (CaP) is a major health problem in males in Western countries. Current therapeutic approaches are limited and many patients die of secondary disease (metastases). There is no cure for metastatic castration-resistant prostate cancer (CRPC). Targeting tumor-associated antigens is fast emerging as an area...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800910791190193
更新日期:2010-05-01 00:00:00
abstract::MicroRNAs (miRNAs) control the expression of approximately 60% of protein-coding genes and regulate cell metabolism, proliferation, differentiation, and apoptosis. Notably, aberrant expression of miRNAs contributes to several diseases including cancer. Accumulating evidence indicates that miRNAs play important roles i...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009616666160216130608
更新日期:2017-01-01 00:00:00