Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Oxidation of cysteine to sulfenic acid has emerged as a biologically relevant post-translational modification with particular importance in redox-mediated signal transduction; however, the identity of modified proteins remains largely unknown. We recently reported DAz-1, a cell-permeable chemical probe capable of detecting sulfenic acid modified proteins directly in living cells. Here we describe DAz-2, an analogue of DAz-1 that exhibits significantly improved potency in vitro and in cells. Application of this new probe for global analysis of the sulfenome in a tumor cell line identifies most known sulfenic acid modified proteins: 14 in total, plus more than 175 new candidates, with further testing confirming oxidation in several candidates. The newly identified proteins have roles in signal transduction, DNA repair, metabolism, protein synthesis, redox homeostasis, nuclear transport, vesicle trafficking, and ER quality control. Cross-comparison of these results with those from disulfide, S-glutathionylation, and S-nitrosylation proteomes reveals moderate overlap, suggesting fundamental differences in the chemical and biological basis for target specificity. The combination of selective chemical enrichment and live-cell compatibility makes DAz-2 a powerful new tool with the potential to reveal new regulatory mechanisms in signaling pathways and identify new therapeutic targets.
ACS Chem Biol 2009 Sep 18
PMID:Mining the thiol proteome for sulfenic acid modifications reveals new targets for oxidation in cells. 1964 9

Nanoparticles, including multiwalled carbon nanotubes (MWNTs), strongly absorb near-infrared (nIR) radiation and efficiently convert absorbed energy to released heat which can be used for localized hyperthermia applications. We demonstrate for the first time that DNA-encasement increases heat emission following nIR irradiation of MWNTs, and DNA-encased MWNTs can be used to safely eradicate a tumor mass in vivo. Upon irradiation of DNA-encased MWNTs, heat is generated with a linear dependence on irradiation time and laser power. DNA-encasement resulted in a 3-fold reduction in the concentration of MWNTs required to impart a 10 degrees C temperature increase in bulk solution temperature. A single treatment consisting of intratumoral injection of MWNTs (100 microL of a 500 microg/mL solution) followed by laser irradiation at 1064 nm, 2.5 W/cm(2) completely eradicated PC3 xenograft tumors in 8/8 (100%) of nude mice. Tumors that received only MWNT injection or laser irradiation showed growth rates indistinguishable from nontreated control tumors. Nonmalignant tissues displayed no long-term damage from treatment. The results demonstrate that DNA-encased MWNTs are more efficient at converting nIR irradiation into heat compared to nonencased MWNTs and that DNA-encased MWNTs can be used safely and effectively for the selective thermal ablation of malignant tissue in vivo.
ACS Nano 2009 Sep 22
PMID:Increased heating efficiency and selective thermal ablation of malignant tissue with DNA-encased multiwalled carbon nanotubes. 1965 28

In the present study, we report the novel application of polyhydroxylated fullerenes (fullerenols) in cancer drug delivery. The facile synthetic procedure for generating multiple hydroxyl groups on the fullerene cage offers scope for high drug loading in addition to conferring hydrophilicity. Doxorubicin, a first line cancer chemotherapeutic, was conjugated to fullerenols through a carbamate linker, achieving ultrahigh loading efficiency. The drug-fullerenol conjugate was found to be relatively stable in phosphate buffer saline but temporally released the active drug when incubated with tumor cell lysate. The fullerenol-doxorubicin conjugate suppressed the proliferation of cancer cell-lines in vitro through a G2-M cell cycle block, resulting in apoptosis. Furthermore, in an in vivo murine tumor model, fullerenol-doxorubicin exhibited comparable antitumor efficacy as free drug without the systemic toxicity of free doxorubicin. Additionally, we demonstrate that the fullerenol platform can be extended to other chemotherapeutic agents, such as the slightly water-soluble cisplatin, and can emerge as a new paradigm in the management of cancer.
ACS Nano 2009 Sep 22
PMID:Fullerenol-cytotoxic conjugates for cancer chemotherapy. 1968 36

A multiwalled carbon nanotube (MWNT)-based drug delivery system was developed by covalently combining carbon nanotubes with the antitumor agent 10-hydroxycamptothecin (HCPT) using hydrophilic diaminotriethylene glycol as the spacer between nanotube and drug moieties. The surface functionalizations of the nanotube were carried out by enrichment of carboxylic groups with optimized oxidization treatment, followed by covalently linking hydrophilic diaminotriethylene glycol via amidation reaction, and then HCPT was chemically attached to carbon nanotubes through a cleavable ester linkage. It is demonstrated that the obtained MWNT-HCPT conjugates are superior in antitumor activity both in vitro and in vivo to clinical HCPT formulation. In vivo single photon emission computed tomography (SPECT) imaging and ex vivo gamma scintillation counting analyses reveal that MWNT-HCPT conjugates have relatively long blood circulation and high drug accumulation in the tumor site. These properties together with the enhanced cell uptake and multivalent presentation of HCPT on a single nanotube benefit substantially the antitumor effects and would boost significantly the applications of carbon nanotubes in the biomedicine field.
ACS Nano 2009 Sep 22
PMID:Covalently combining carbon nanotubes with anticancer agent: preparation and antitumor activity. 1970 92

The analysis of panels of nucleic acid biomarkers offers valuable diagnostic and prognostic information for cancer management. A cost-effective, highly sensitive electronic chip would offer an ideal platform for clinical biomarker readout and would have maximal utility if it was (i) multiplexed, enabling on-chip assays of multiple biomarkers, and (ii) able to perform direct (PCR-free) readout of disease-related genes. Here we report a chip onto which we integrate novel nanostructured microelectrodes and with which we directly detect cancer biomarkers in heterogeneous biological samples-both cell extracts and tumor tissues. Coarse photolithographic microfabrication defines a multiplexed sensing array; bottom-up fabrication of nanostructured microelectrodes then provides sensing elements. We analyzed a panel of mRNA samples for prostate cancer related gene fusions using the chip. We accurately identified gene fusions that correlate with aggressive prostate cancer and distinguished these from fusions associated with slower-progressing forms of the disease. The multiplexed nanostructured microelectrode integrated circuit reported herein provides direct, amplification-free, sample-to-answer in under 1 h using the 10 ng of mRNA readily available in biopsy samples.
ACS Nano 2009 Oct 27
PMID:Direct profiling of cancer biomarkers in tumor tissue using a multiplexed nanostructured microelectrode integrated circuit. 1973 19

Nonspecific distribution of chemotherapeutic drugs (such as paclitaxel) is a major factor contributing to side effects and poor clinical outcomes in the treatment of human head and neck cancer. To develop novel drug delivery systems with enhanced efficacy and minimized adverse effects, we synthesized a ternary conjugate heparin-folic acid-paclitaxel (HFT), loaded with additional paclitaxel (T). The resulting nanoparticle, HFT-T, is expected to retain the antitumor activity of paclitaxel and specifically target folate receptor (FR)-expressing tumors, thereby increasing the bioavailability and efficacy of paclitaxel. In vitro experiments found that HFT-T selectively recognizes FR-positive human head and neck cancer cell line KB-3-1, displaying higher cytotoxicity compared to the free form of paclitaxel. In a subcutaneous KB-3-1 xenograft model, HFT-T administration enhanced the specific delivery of paclitaxel into tumor tissues and remarkably improved antitumor efficacy of paclitaxel. The average tumor volume in the HFT-T treatment group was 92.9 +/- 78.2 mm(3) vs 1670.3 +/- 286.1 mm(3) in the mice treated with free paclitaxel. Furthermore, paclitaxel tumors showed a resurgence of growth after several weeks of treatment, but this was not observed with HFT-T. This indicates that HFT-T could be more effective in preventing tumors from developing drug resistance. No significant acute in vivo toxicity was observed. These results indicate that specific delivery of paclitaxel with a ternary structured nanoparticle (HFT-T) targeting FR-positive tumor is a promising strategy to enhance chemotherapy efficacy and minimize adverse effects.
ACS Nano 2009 Oct 27
PMID:HFT-T, a targeting nanoparticle, enhances specific delivery of paclitaxel to folate receptor-positive tumors. 1976 Nov 91

Honokiol (HK) can efficiently inhibit the growth of tumors. However, its clinical applications have been restricted by its extreme hydrophobicity. We hope to improve its water solubility by nanotechnology. And we wonder whether a novel honokiol nanoparticles-loaded thermosensitive poly(ethylene glycol)-poly(epsilon-caprolactone)-poly(ethylene glycol) (PEG-PCL-PEG, PECE) hydrogel (HK-hydrogel) could improve the therapeutic efficacy on malignant pleural effusion (MPE). To evaluate the therapeutic effects of HK-hydrogel on MPE, MPE-bearing mice were administered intrapleurally with HK-hydrogel, HK nanoparticles (HK-NP), blank hydrogel, or normal saline (NS) at days 4 and 11 after Lewis lung carcinoma (LLC) cells inoculation, respectively. Pleural tumor foci and survival time were observed, and antiangiogenesis of HK-hydrogel was determined by CD31. Histological analysis and assessment of apoptotic cells were also conducted in tumor tissues. HK-hydrogel reduced the number of pleural tumor foci, while prolonging the survival time of MPE-bearing mice, more effectively, as compared with control groups. In addition, HK-hydrogel successfully inhibited angiogenesis as assessed by CD31 (P < 0.05). Histological analysis of pleural tumors exhibited that HK-hydrogel led to the increased rate of apoptosis. This work is important for the further application of HK-hydrogel in the treatment of MPE.
ACS Nano 2009 Dec 22
PMID:Honokiol nanoparticles in thermosensitive hydrogel: therapeutic effects on malignant pleural effusion. 1992 11

We report the synthesis of novel acid-responsive therapeutic nanoparticles (NPs) with sub-100 nm size consisting of polymer--cisplatin conjugates. The uniqueness of these drug delivery polymeric NPs lies in the covalent conjugation of each cisplatin drug to the hydrophobic segment of two biocompatible diblock copolymer chains through a hydrazone bond, resulting in highly differential drug release profile at different environmental acidity. We demonstrate that the synthesized polymer--cisplatin conjugates can readily precipitate to form sub-100 nm NPs in aqueous solution due to their very low critical micelle concentration (CMC). The resulting NPs show well-controlled cisplatin loading yield, excellent acid-responsive drug release kinetics, and enhanced in vitro cytotoxicity against ovarian cancer cells as compared to free cisplatin. As an environmentally sensitive drug delivery vehicle, these NPs can potentially minimize the drug loss during NP circulation in the blood, where the pH value is neutral, and trigger rapid intracellular drug release after the NPs are endocytosed by the target cells. This characteristic drug release profile holds the promise to suppress cancer cell chemoresistance by rapidly releasing a high dose of chemotherapy drugs inside the tumor cells, thereby improving the therapeutic efficacy of the drug payload.
ACS Nano 2010 Jan 26
PMID:Polymer--cisplatin conjugate nanoparticles for acid-responsive drug delivery. 2003 97

The targeted delivery of therapeutics to tumors remains an important challenge in cancer nanomedicine. Attaching nanoparticles to cells that have tumoritropic migratory properties is a promising modality to address this challenge. Here we describe a technique to create nanoparticulate cellular patches that remain attached to the membrane of cells for up to 2 days. NeutrAvidin-coated nanoparticles were anchored on cells possessing biotinylated plasma membrane. Human bone marrow derived mesenchymal stem cells with nanoparticulate patches retained their inherent tumoritropic properties as shown using a tumor model in a 3D extracellular matrix. Additionally, human umbilical vein endothelial cells with nanoparticulate patches were able to retain their functional properties and form multicellular structures as rapidly as unmodified endothelial cells. These results provide a novel strategy to actively deliver nanostructures and therapeutics to tumors utilizing stem cells as carriers and also suggest that nanoparticulate cellular patches may have applications in tissue regeneration.
ACS Nano 2010 Feb 23
PMID:Nanoparticulate cellular patches for cell-mediated tumoritropic delivery. 2012 Dec 15

Target-activatable fluorogenic probes based on gold nanoparticles (AuNPs) functionalized with self-assembled heterogeneous monolayers of dye-labeled peptides and poly(ethylene glycol) have been developed to visualize proteolytic activity in vivo. A one-step synthesis strategy that allows simple generation of surface-defined AuNP probe libraries is presented as a means of tailoring and evaluating probe characteristics for maximal fluorescence enhancement after protease activation. Optimal AuNP probes targeted to trypsin and urokinase-type plasminogen activator required the incorporation of a dark quencher to achieve 5- to 8-fold signal amplification. These probes exhibited extended circulation time in vivo and high image contrast in a mouse tumor model.
ACS Nano 2010 Mar 23
PMID:Self-assembled gold nanoparticle molecular probes for detecting proteolytic activity in vivo. 2014 6


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