472 research outputs found
In Vitro and in vivo anti-tumoral effects of the flavonoid apigenin in malignant mesothelioma
Malignant mesothelioma (MM) is a tumor arising from mesothelium. MM patients' survival is poor. The polyphenol 4',5,7,-trihydroxyflavone Apigenin (API) is a "multifunctional drug". Several studies have demonstrated API anti-tumoral effects. However, little is known on the in vitro and in vivo anti-tumoral effects of API in MM. Thus, we analyzed the in vitro effects of API on cell proliferation, cell cycle regulation, pro-survival signaling pathways, apoptosis, and autophagy of human and mouse MM cells. We evaluated the in vivo anti-tumor activities of API in mice transplanted with MM #40a cells forming ascites. API inhibited in vitro MM cells survival, increased reactive oxygen species intracellular production and induced DNA damage. API activated apoptosis but not autophagy. API-induced apoptosis was sustained by the increase of Bax/Bcl-2 ratio, increase of p53 expression, activation of both caspase 9 and caspase 8, cleavage of PARP-1, and increase of the percentage of cells in subG1 phase. API treatment affected the phosphorylation of ERK1/2, JNK and p38 MAPKs in a cell-type specific manner, inhibited AKT phosphorylation, decreased c-Jun expression and phosphorylation, and inhibited NF-κB nuclear translocation. Intraperitoneal administration of API increased the median survival of C57BL/6 mice intraperitoneally transplanted with #40a cells and reduced the risk of tumor growth. Our findings may have important implications for the design of MM treatment using API
Curcumin blocks autophagy and activates apoptosis of malignant mesothelioma cell lines and increases the survival of mice intraperitoneally transplanted with a malignant mesothelioma cell line
Malignant mesothelioma (MM) is a primary tumor arising from the serous membranes. The resistance of MM patients to conventional therapies, and the poor patients' survival, encouraged the identification of molecular targets for MM treatment. Curcumin (CUR) is a "multifunctional drug". We explored the in vitro effects of CUR on cell proliferation, cell cycle regulation, pro-survival signaling pathways, apoptosis, autophagy of human (MM-B1, H-Meso-1, MM-F1), and mouse (#40a) MM cells. In addition, we evaluated the in vivo anti-tumor activities of CUR in C57BL/6 mice intraperitoneally transplanted with #40a cells forming ascites.CUR in vitro inhibited MM cells survival in a dose- and time-dependent manner and increased reactive oxygen species'intracellular production and induced DNA damage. CUR triggered autophagic flux, but the process was then blocked and was coincident with caspase 8 activation which activates apoptosis. CUR-mediated apoptosis was supported by the increase of Bax/Bcl-2 ratio, increase of p53 expression, activation of caspase 9, cleavage of PARP-1, increase of the percentage of cells in the sub G1 phase which was reduced (MM-F1 and #40a) or abolished (MM-B1 and H-Meso-1) after MM cells incubation with the apoptosis inhibitor Z-VAD-FMK. CUR treatment stimulated the phosphorylation of ERK1/2 and p38 MAPK, inhibited that of p54 JNK and AKT, increased c-Jun expression and phosphorylation and prevented NF-κB nuclear translocation. Intraperitoneal administration of CUR increased the median survival of C57BL/6 mice intraperitoneally transplanted with #40a cells and reduced the risk of developing tumors. Our findings may have important implications for the design of MM treatment using CUR
Trojan Horse nanotheranostics with dual transformability and multifunctionality for highly effective cancer treatment.
Nanotheranostics with integrated diagnostic and therapeutic functions show exciting potentials towards precision nanomedicine. However, targeted delivery of nanotheranostics is hindered by several biological barriers. Here, we report the development of a dual size/charge- transformable, Trojan-Horse nanoparticle (pPhD NP) for delivery of ultra-small, full active pharmaceutical ingredients (API) nanotheranostics with integrated dual-modal imaging and trimodal therapeutic functions. pPhD NPs exhibit ideal size and charge for drug transportation. In tumour microenvironment, pPhD NPs responsively transform to full API nanotheranostics with ultra-small size and higher surface charge, which dramatically facilitate the tumour penetration and cell internalisation. pPhD NPs enable visualisation of biodistribution by near-infrared fluorescence imaging, tumour accumulation and therapeutic effect by magnetic resonance imaging. Moreover, the synergistic photothermal-, photodynamic- and chemo-therapies achieve a 100% complete cure rate on both subcutaneous and orthotopic oral cancer models. This nanoplatform with powerful delivery efficiency and versatile theranostic functions shows enormous potentials to improve cancer treatment
Violacein, an indole-derived purple-colored natural pigment produced by Janthinobacterium lividum, inhibits the growth of head and neck carcinoma cell lines both in vitro and in vivo
Violacein (VIO; 3-[1,2-dihydro-5-(5-hydroxy-1H-indol-3-yl)-2-oxo-3H-pyrrol-3-ylidene]-1,3-dihydro-2H-indol-2-one), an indole-derived purple-colored pigment, produced by a limited number of Gram-negative bacteria species, including Chromobacterium violaceum and Janthinobacterium lividum, has been demonstrated to have anti-cancer activity, as it interferes with survival transduction signaling pathways in different cancer models. Head and neck carcinoma (HNC) represents the sixth most common and one of the most fatal cancers worldwide. We determined whether VIO was able to inhibit head and neck cancer cell growth both in vitro and in vivo. We provide evidence that VIO treatment of human and mouse head and neck cancer cell lines inhibits cell growth and induces autophagy and apoptosis. In fact, VIO treatment increased PARP-1 cleavage, the Bax/Bcl-2 ratio, the inhibition of ERK1 and ERK2 phosphorylation, and the expression of light chain 3-II (LC3-II). Moreover, VIO was able to induce p53 degradation, cytoplasmic nuclear factor kappa B (NF-κB) accumulation, and reactive oxygen species (ROS) production. VIO induced a significant increase in ROS production. VIO administration was safe in BALB/c mice and reduced the growth of transplanted salivary gland cancer cells (SALTO) in vivo and prolonged median survival. Taken together, our results indicate that the treatment of head and neck cancer cells with VIO can be useful in inhibiting in vivo and in vitro cancer cell growth. VIO may represent a suitable tool for the local treatment of HNC in combination with standard therapies
Triaquabis{2-methoxy-6-[(phenyliminiumyl)methyl]phenolate-κO 1}manganese(II) dinitrate
The crystal structure of the title compound, [Mn(C14H13NO2)2(H2O)3](NO3)2, is comprised of two Schiff base 2-methoxy-6-(N-phenylcarboximidoyl)phenol (HL) ligands and three coordinated water molecules. The MnII ion lies on a twofold axis that bisects one water O atom. The coordination sphere of the five-coordinate Mn atom is completed by the two monodentate HL ligands and three coordinated water molecules binding through their O atoms, affording a distorted tetragonal–pyramidal geometry. In the phenolate ligands, the hydroxy H atom transfers to the imine N atom. This H atom is also involved in an intramolecular N—H⋯O hydrogen bond that imposes a nearly planar conformation on each ligand, with dihedral angles of 2.78 (3) and 2.43 (5)° between the aromatic rings of each ligand. In the crystal, molecules are linked by intermolecular O—H⋯O hydrogen bonds
In vitro and in vivo inhibition of breast cancer cell growth by targeting the Hedgehog/GLI pathway with SMO (GDC-0449) or GLI (GANT-61) inhibitors.
Aberrant Hedgehog (Hh)/glioma-associated oncogene (GLI) signaling has
been implicated in cancer progression. Here, we analyzed GLI1, Sonic Hedgehog
(Shh) and NF-κB expression in 51 breast cancer (ductal carcinoma) tissues using
immunohistochemistry. We found a positive correlation between nuclear GLI1
expression and tumor grade in ductal carcinoma cases. Cytoplasmic Shh staining
significantly correlated with a lower tumor grade. Next, the in vitro effects of two
Hh signaling pathway inhibitors on breast cancer cell lines were evaluated using the
Smoothened (SMO) antagonist GDC-0449 and the direct GLI1 inhibitor GANT-61.
GDC-0449 and GANT-61 exhibited the following effects: a) inhibited breast cancer
cell survival; b) induced apoptosis; c) inhibited Hh pathway activity by decreasing
the mRNA expression levels of GLI1 and Ptch and inhibiting the nuclear translocation
of GLI1; d) increased/decreased EGFR and ErbB2 protein expression, reduced p21-
Ras and ERK1/ERK2 MAPK activities and inhibited AKT activation; and e) decreased
the nuclear translocation of NF-κB. However, GANT-61 exerted these effects more
effectively than GDC-0449. The in vivo antitumor activities of GDC-0449 and GANT-
61 were analyzed in BALB/c mice that were subcutaneously inoculated with mouse
breast cancer (TUBO) cells. GDC-0449 and GANT-61 suppressed tumor growth of
TUBO cells in BALB/c mice to different extents. These findings suggest that targeting
the Hh pathway using antagonists that act downstream of SMO is a more efficient
strategy than using antagonists that act upstream of SMO for interrupting Hh signaling
in breast cancer
A general model for collaboration networks
In this paper, we propose a general model for collaboration networks.
Depending on a single free parameter "{\bf preferential exponent}", this model
interpolates between networks with a scale-free and an exponential degree
distribution. The degree distribution in the present networks can be roughly
classified into four patterns, all of which are observed in empirical data. And
this model exhibits small-world effect, which means the corresponding networks
are of very short average distance and highly large clustering coefficient.
More interesting, we find a peak distribution of act-size from empirical data
which has not been emphasized before of some collaboration networks. Our model
can produce the peak act-size distribution naturally that agrees with the
empirical data well.Comment: 10 pages, 10 figure
Simulation of Ion Irradiation of Nuclear Materials and Comparison with Experiment
Radiation defects generated in various nuclear materials such as Mo and CeO2, used as a surrogate material for UO2, formed by sub-MeV Xe and Kr ion implantations were studied via TRIM and MD codes. Calculated results were compared with defect distributions in CeO2 crystals obtained from experiments by implantation of these ions at
the doses of 11017 ions/cm2 at several temperatures. A combination of in situ TEM
(Transmission Electron Microscopy) and ex situ TEM experiments on Mo were used to
study the evolution of defect clusters during implantation of Xe and Kr ions at energies of
150-700 keV, depending on the experimental conditions. The simulation and irradiation
were performed on thin film single crystal materials. The formation of defects, dislocations,
and solid-state precipitates were studied by simulation and compared to experiment. Void
and bubble formation rates are estimated based on a new mesoscale approach that
combines experiment with the kinetic models validated by atomistic and Ab-initio simulations. Various sets of quantitative experimental results were obtained to characterize the dose and temperature effects of irradiation. These experimental results include size distributions of dislocation loops, voids and gas bubble structures created by irradiation
- …