There is convincing epidemiological and experimental evidence that capsaicin, a potent natural transient receptor potential cation channel vanilloid member 1 (TRPV1) agonist, has anticancer activity. ...However, capsaicin cannot be given systemically in large doses, because of its induction of acute pain and neurological inflammation. MRS1477, a dihydropyridine derivative acts as a positive allosteric modulator of TRPV1, if added together with capsaicin, but is ineffective, if given alone. Addition of MRS1477 evoked Ca2+ signals in MCF7 breast cancer cells, but not in primary breast epithelial cells. This indicates that MCF7 cells not only express functional TRPV1 channels, but also produce endogenous TRPV1 agonists. We investigated the effects of MRS1477 and capsaicin on cell viability, caspase-3 and -9 activities and reactive oxygen species production in MCF7 cells. The fraction of apoptotic cells was increased after 3 days incubation with capsaicin (10 μM) paralleled by increased reactive oxygen species production and caspase activity. These effects were even more pronounced, when cells were incubated with MRS1477 (2 μM) either alone or together with CAPS (10 μM). Capsazepine, a TRPV1 blocker, inhibited both the effect of capsaicin and MRS1477. Whole-cell patch clamp recordings revealed that capsaicin-evoked TRPV1-mediated current density levels were increased after 3 days incubation with MRS1477 (2 μM). However, the tumor growth in MCF7 tumor-bearing immunodeficient mice was not significantly decreased after treatment with MRS1477 (10 mg/ kg body weight, i.p., injection twice a week). In conclusion, in view of a putative in vivo treatment with MRS1477 or similar compounds further optimization is required.
A novel and simple analytical procedure has been developed for the trace-level determination of lanthanides (rare-earth elements) in uranium-bearing materials by inductively coupled plasma ...sector-field mass spectrometry (ICP-SFMS). The method involves a selective extraction chromatographic separation of lanthanides using TRU™ resin followed by ICP-SFMS analysis. The limits of detection of the method proposed is in the low pg
g
−1 range, which are approximately two orders of magnitude better than that of without chemical separation. The method was validated by the measurement of reference material and applied for the analysis of uranium ore concentrates (yellow cakes) for nuclear forensic purposes, as a potential application of the methodology.
The close proximity of adipose tissue and mammary epithelium predispose involvement of adipose cells in breast cancer development. Adipose-tissue stem cells (ASCs) contribute to tumor stroma and ...promote growth of cancer cells. In our previous study, we have shown that murine ASCs, which undergo polyploidization during their prolonged
culturing, enhanced the proliferation of 4T1 murine breast cancer cells in IGF1 dependent manner.
In the present study, our aim was to clarify the regulation of ASC-derived IGF1.
4T1 murine breast carcinoma cells were co-transplanted with visceral fat-derived ASCs (vASC) or with the polyploid ASC.B6 cell line into female BALB/c mice and tumor growth and lung metastasis were monitored. The conditioned media of vASCs and ASC.B6 cells were subjected to LC-MS/MS analysis and the production of IGFBP2 was verified by Western blotting. The regulatory effect was examined by adding recombinant IGFBP2 to the co-culture of ASC.B6 and 4T1. Akt/protein kinase B (PKB) activation was detected by Western blotting.
Polyploid ASCs promoted the tumor growth and metastasis more potently than vASCs with normal karyotype. vASCs produced the IGF1 regulator IGFBP2, which inhibited proliferation of 4T1 cells. Downregulation of IGFBP2 by polyploidization of ASCs and enhanced secretion of IGF1 allowed survival signaling in 4T1 cells, leading to Akt phosphorylation.
Our results implicate that ASCs in the tumor microenvironment actively regulate the growth of breast cancer cells through the IGF/IGFBP system.
This case study presents a fast and reliable method of combining strontium isotope ratios (⁸⁷Sr/⁸⁶Sr) with a multielement pattern (Rb, Sr, Y, Zr, Mo, Cd, Ba, Pb, Th, U, Mg, Ca, Sc, Ti, Cr, Mn, Fe, ...Co, Ni, Cu, Zn, As and rare earth elements) by means of inductively coupled plasma mass spectrometry (ICP-MS) to establish a unique fingerprint of authentic Szegedi Fűszerpaprika (PDO) and classify authentic and purchased paprika from different known, declared and unknown geographical origin using multivariate statistical tools (principal component and canonical discriminant analysis). Since paprika represents a processed spice, alterations in element and Sr isotopic composition throughout the production process were investigated. The Sr source in the final product was identified to stem from bioavailable Sr sources in soil. Therefore, the ammonium nitrate extract of a soil is sufficient to establish a Sr fingerprint for agricultural products of a region. As a consequence, the spice paprika can be traced back to its geographical origin even after processing.
The B6.Cg-Tg(Thy1-YFP)16Jrs/J transgenic mouse strain, widely used to study neuronal development and regeneration, expresses the yellow fluorescent protein (YFP) in the peripheral nerves and the ...central nervous system under the control of regulatory sequences of the Thy1 gene. The Thy1 (CD90) cell surface glycoprotein is present on many cell types besides neurons, and is known to be involved in cell adhesion, migration and signal transduction. We hypothesized that Thy1-activating conditions could probably activate the truncated Thy1 regulatory sequences used in the Thy1-YFP construct, resulting in YFP transgene expression outside the nervous system. We demonstrated that the stroma of subcutaneous tumours induced by the injection of 4T1 or MC26 carcinoma cells into BALB/c(Thy1-YFP) mice, carrying the same construct, indeed expressed the YFP transgene. In the tumour mass, the yellow-green fluorescent stromal cells were clearly distinguishable from 4T1 carcinoma cells stably transfected with red fluorescent protein. Local inflammation induced by subcutaneous injection of complete Freund's adjuvant, as well as the experimental wound-healing milieu, also triggered YFP fluorescence in both the BALB/c(Thy1-YFP) and B6.Cg-Tg(Thy1-YFP)16Jrs/J mice, pointing to eventual overlapping pathways of wound-healing, inflammation and tumour growth.
Abstract Galectin-1 (Gal-1) has been implicated in tumor progression partly via the induction of T-cell apoptosis. However the mechanism of Gal-1 induced T-cell death was mostly studied using ...recombinant, soluble Gal-1 producing controversial results. To explore the true mechanism of Gal-1 and hence tumor cell-induced T-cell death, we applied co-cultures of tumor cells and T-cells thus avoiding artificial circumstances generated using recombinant protein. T-cells died when co-cultured with Gal-1-expressing but survived with Gal-1 non-expressing tumor cells. Removing tumor cell surface Gal-1 or knocking down Gal-1 expression resulted in diminution of T-cell apoptosis. Gal-1 transgenic or soluble Gal-1 treated HeLa cells became cytotoxic. Stimulation of apoptosis required interaction between the tumor and T-cells, presence of p56lck and ZAP70, decrease of mitochondrial membrane potential and caspase activation. Hence tumor cell-derived Gal-1 might efficiently contribute to tumor self-defense. Moreover this system resolves the discrepancies obtained using recombinant Gal-1 in T-cell apoptosis studies.
This paper presents the MPT-GRE software, a novel multipath communication technology founded on the Generic Routing Encapsulation (GRE) protocol in UDP tunneling RFC specification. It enables the ...creation of a GRE protocolbased UDP tunnel built on several communication channels. On the other hand, MPTCP is one of the most typical representatives among multipath communication technologies, basing its operation on the utilization of TCP subflows. The authors compare the path-aggregation capabilities of these two technologies using four Fast Ethernet channels. The tests were carried out with the iperf3 network bandwidth measurement tool, and while transferring data using the FTP protocol over both IPv4 and IPv6.
Bone marrow derived mesenchymal stromal cells (MSCs) have recently been implicated as one source of the tumor-associated stroma, which plays essential role in regulating tumor progression. In spite ...of the intensive research, the individual factors in MSCs controlling tumor progression have not been adequately defined. In the present study we have examined the role of galectin-1 (Gal-1), a protein highly expressed in tumors with poor prognosis, in MSCs in the course of tumor development. Co-transplantation of wild type MSCs with 4T1 mouse breast carcinoma cells enhances the incidence of palpable tumors, growth, vascularization and metastasis. It also reduces survival compared to animals treated with tumor cells alone or in combination with Gal-1 knockout MSCs. In vitro studies show that the absence of Gal-1 in MSCs does not affect the number of migrating MSCs toward the tumor cells, which is supported by the in vivo migration of intravenously injected MSCs into the tumor. Moreover, differentiation of endothelial cells into blood vessel-like structures strongly depends on the expression of Gal-1 in MSCs. Vital role of Gal-1 in MSCs has been further verified in Gal-1 knockout mice. By administering B16F10 melanoma cells into Gal-1 deficient animals, tumor growth is highly reduced compared to wild type animals. Nevertheless, co-injection of wild type but not Gal-1 deficient MSCs results in dramatic tumor growth and development.These results confirm that galectin-1 is one of the critical factors in MSCs regulating tumor progression.
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▶ Inverse correlation between the activities in glucose oxidation and CO oxidation. ▶ Support effect is more significant than small gold particle size in glucose oxidation. ▶ Weak ...metal–support interaction favors the activity in glucose oxidation.
Two series of gold catalysts supported on TiO
2, SiO
2, and CeO
2 have been prepared by colloidal gold deposition with 2
wt% of nominal gold loading. The diameter of gold particle stabilized by polyvinylalcohol (PVA) or by tannic acid-citrate was 2–3
nm and 6–7
nm, which increased to 5–7
nm and 7–13
nm, respectively, after calcination in air. Catalytic activities were investigated and compared in CO oxidation and glucose oxidation reactions. Inverse correlation was found between the activities in glucose oxidation and CO oxidation suggesting that the mechanisms are different. Besides the high dispersion the nature of the support seems to play a significant role in the liquid phase reaction.
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