| 1. |
- Bai, Lichen, et al.
(författare)
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Visible-light-driven selective oxidation of benzyl alcohol and thioanisole by molecular ruthenium catalyst modified hematite
- 2016
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Ingår i: Chemical Communications. - : Royal Society of Chemistry. - 1359-7345 .- 1364-548X. ; 52:62, s. 9711-9714
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Tidskriftsartikel (refereegranskat)abstract
- Molecular ruthenium catalysts were found to selectively catalyze the oxidation of thioanisole to sulfoxide with a yield up to 100% in the presence of visible light and sacrificial reagents when they were anchored onto hematite powder. The composite photocatalysts also showed about 5 times higher efficiencies in benzyl alcohol oxidation than the system composed of dispersed molecular catalysts and hematite particles in aqueous solution. A photoelectrochemical cell based on a molecular catalyst modified hematite photoanode was further fabricated, which exhibited high activity towards the oxidation of organic substrates.
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| 2. |
- Cao, Renhai, et al.
(författare)
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Collaborative interplay between FGF-2 and VEGF-C promotes lymphangiogenesis and metastasis
- 2012
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 109:39, s. 15894-15899
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Tidskriftsartikel (refereegranskat)abstract
- Interplay between various lymphangiogenic factors in promoting lymphangiogenesis and lymphatic metastasis remains poorly understood. Here we show that FGF-2 and VEGF-C, two lymphangiogenic factors, collaboratively promote angiogenesis and lymphangiogenesis in the tumor microenvironment, leading to widespread pulmonary and lymph-node metastases. Coimplantation of dual factors in the mouse cornea resulted in additive angiogenesis and lymphangiogenesis. At the molecular level, we showed that FGFR-1 expressed in lymphatic endothelial cells is a crucial receptor that mediates the FGF-2-induced lymphangiogenesis. Intriguingly, the VEGFR-3-mediated signaling was required for the lymphatic tip cell formation in both FGF-2- and VEGF-C-induced lymphangiogenesis. Consequently, a VEGFR-3-specific neutralizing antibody markedly inhibited FGF-2-induced lymphangiogenesis. Thus, the VEGFR-3-induced lymphatic endothelial cell tip cell formation is a prerequisite for FGF-2-stimulated lymphangiogenesis. In the tumor microenvironment, the reciprocal interplay between FGF-2 and VEGF-C collaboratively stimulated tumor growth, angiogenesis, intratumoral lymphangiogenesis, and metastasis. Thus, intervention and targeting of the FGF-2- and VEGF-C-induced angiogenic and lymphangiogenic synergism could be potentially important approaches for cancer therapy and prevention of metastasis.
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| 3. |
- Eleonora Hedlund, Eva-Maria, et al.
(författare)
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Tumor cell-derived placental growth factor sensitizes antiangiogenic and antitumor effects of anti-VEGF drugs
- 2013
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 110:2, s. 654-659
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Tidskriftsartikel (refereegranskat)abstract
- The role of placental growth factor (PlGF) in modulation of tumor angiogenesis and tumor growth remains an enigma. Furthermore, anti-PlGF therapy in tumor angiogenesis and tumor growth remains controversial in preclinical tumor models. Here we show that in both human and mouse tumors, PlGF induced the formation of dilated and normalized vascular networks that were hypersensitive to anti-VEGF and anti-VEGFR-2 therapy, leading to dormancy of a substantial number of avascular tumors. Loss-of-function using plgf shRNA in a human choriocarcinoma significantly accelerated tumor growth rates and acquired resistance to anti-VEGF drugs, whereas gain-of-function of PlGF in a mouse tumor increased anti-VEGF sensitivity. Further, we show that VEGFR-2 and VEGFR-1 blocking antibodies displayed opposing effects on tumor angiogenesis. VEGFR-1 blockade and genetic deletion of the tyrosine kinase domain of VEGFR-1 resulted in enhanced tumor angiogenesis. These findings demonstrate that tumor-derived PlGF negatively modulates tumor angiogenesis and tumor growth and may potentially serve as a predictive marker of anti-VEGF cancer therapy.
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| 4. |
- Ji, Hong, et al.
(författare)
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TNFR1 mediates TNF-alpha-induced tumour lymphangiogenesis and metastasis by modulating VEGF-C-VEGFR3 signalling
- 2014
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Ingår i: Nature Communications. - : Nature Publishing Group: Nature Communications. - 2041-1723. ; 5:4944
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Tidskriftsartikel (refereegranskat)abstract
- Inflammation and lymphangiogenesis are two cohesively coupled processes that promote tumour growth and invasion. Here we report that TNF-alpha markedly promotes tumour lymphangiogenesis and lymphatic metastasis. The TNF-alpha-TNFR1 signalling pathway directly stimulates lymphatic endothelial cell activity through a VEGFR3-independent mechanism. However, VEGFR3-induced lymphatic endothelial cell tips are a prerequisite for lymphatic vessel growth in vivo, and a VEGFR3 blockade completely ablates TNF-alpha-induced lymphangiogenesis. Moreover, TNF-alpha-TNFR1-activated inflammatory macrophages produce high levels of VEGF-C to coordinately activate VEGFR3. Genetic deletion of TNFR1 (Tnfr1(-/-)) in mice or depletion of tumour-associated macrophages (TAMs) virtually eliminates TNF-alpha-induced lymphangiogenesis and lymphatic metastasis. Gain-of-function experiments show that reconstitution of Tnfr1(+/+) macrophages in Tnfr1(+/+) mice largely restores tumour lymphangiogenesis and lymphatic metastasis. These findings shed mechanistic light on the intimate interplay between inflammation and lymphangiogenesis in cancer metastasis, and propose therapeutic intervention of lymphatic metastasis by targeting the TNF-alpha-TNFR1 pathway.
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| 5. |
- Nilsonne, Gustav, et al.
(författare)
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Selenite induces apoptosis in sarcomatoid malignant mesothelioma cells through oxidative stress
- 2006
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Ingår i: Free Radical Biology and Medicine. - Stockholm : Karolinska Institutet, Dept of Laboratory Medicine. - 0891-5849.
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Tidskriftsartikel (refereegranskat)abstract
- Malignant mesothelioma cells differentiate into sarcomatoid or epithelioid phenotypes. The sarcomatoid cell type is more resistant to chemotherapy and yields a worse prognosis. We have investigated whether selenite alone and in combination with doxorubicin induced apoptosis in variously differentiated mesothelioma cells. Selenite in concentrations that could potentially be administered to patients strongly inhibited the growth of the sarcomatoid mesothelioma cells (IC 50 = 7.5 µM), whereas epithelioid cells were more sensitive to doxorubicin. Benign mesothelial cells remained largely unaffected. Selenite potentiates doxorubicin treatment. Apoptosis was the dominating mode of cell death. The toxicity of selenite was mediated by oxidative stress. Furthermore the activity of the thioredoxin system was directly dependent on the concentration of selenite. This offers a possible mechanism of action of selenite treatment. Our findings suggest that selenite is a promising new drug for the treatment of malignant mesothelioma.
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| 6. |
- Sun, Xiaojuan, et al.
(författare)
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Proteasome inhibitor PSI induces apoptosis in human mesothelioma cells
- 2006
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Ingår i: Cancer Letters. - : Elsevier BV. - 0304-3835 .- 1872-7980. ; 232:2, s. 161-169
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Tidskriftsartikel (refereegranskat)abstract
- Malignant mesothelioma is an increasingly common tumor with an almost 100% mortality rate. It is refractory to conventional treatment. We have previously shown with SSH and microarray that the mRNA expression level of proteasome is higher in epithelioid mesothelioma cell lines than in sarcomatoid ones. This study evaluates the differential apoptotic effect of proteasome inhibitors on both of these mesothelioma sub-lines. Proteasome inhibitors show substantial anti-tumor activity in some tumor cells in vitro and in vivo, but the effects on mesothelioma cells has not been studied. The viability of mesothelioma cells was reduced in a dose- and time-dependent manner by the proteasome inhibitors tested; PSI was effective with a low dose, but higher concentrations were needed for calpain inhibitor I. The epithelioid mesothelioma cells are more sensitive to the inhibitors than the sarcomatoid ones, their IC50 after 24 h of treatment with PSI being 4 and 16 microm, respectively. Other mesothelioma cell lines show similar sensitivity. PSI seemed to decrease mesothelioma viability by inducing apoptosis, as verified by cell morphology, Western blotting analysis of caspase 3 cleavage, and flow-cytometric analysis. In conclusion, PSI, a representative agent that reduces viability and induces apoptosis of mesothelioma cells, might be useful in the treatment of patients with mesothelioma, especially of epithelioid phenotype.
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| 7. |
- Sun, Xiaojuan
(författare)
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Studies on mesothelial differentiation : prognostic and therapeutic approaches to malignant mesothelioma
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Malignant mesothelioma (MM), a tumor with a poor prognosis, causes the death of most patients within a year of diagnosis since various treatments seem to have little effect on its outcome. The biological behavior of MM varies greatly, and this heterogeneity is related to its morphology, which may be epithelioid, sarcomatoid (fibroblastoid) or biphasic, the sarcomatoid phenotype being associated with a shorter survival. The mechanisms by which the MM cells differentiate into epithelioid or fibroblastoid phenotypes are largely unknown. We used a MM cell line that, depending on the serum supplementation, differentiates into sublines with two phenotypes, the epithelioid STAV-AB and fibroblastoid STAV-FCS. A similar variability in growth phenotype can also be seen in benign mesothelial cells that have exfoliated into effusions. In short-term cultures, such cells may grow with a fibroblastoid or epithelioid morphology. The growth patterns obtained remain stable during several passages and the benign and malignant cells can be used as in vitro models when studying mechanisms of mesothelial differentiation. The aims of the present study were to determine the candidate genes involved in the differentiation of benign and malignant mesothelium. This was done by using Suppression Subtractive Hybridization (SSH) and Microarray techniques, and the findings were confirmed in vitro and in vivo. Such screening of gene expressions may be of value in finding diagnostic markers and targets for novel treatments of MM. Both the benign and malignant epithelioid cells expressed more genes related to specialized functions associated with metabolism, cellular defense, apoptosis and differentiation, while those related to growth factors and their receptors were more abundantly expressed in the sarcomatoid phenotype. These findings accord with the view that the fibroblastoid cell type represents a less differentiated stage than the epithelioid ones. Our data indicate that the different tumor phenotypes use different driving mechanisms, and the heterogeneity of the tumor may therefore be one explanation for the poor response to chemotherapy. A better response might be expected if targets were selected according to the individual phenotypes. The targeting of two differentiation-associated functions induced apoptosis in vitro. The thioredoxin/thioredoxin reductase (Trx/TR) system was differentially expressed, although extremely large amounts were present in both cell sublines. This may make the cells particularly sensitive to selenite, and this salt reduced the cell viability of MM cells, especially in those with fibroblast-like phenotype. A combination with doxorubicin was synergistic, and markedly affected on both cell phenotypes. A similar induction of apoptosis occurred in the epithelioid cells, after giving proteasome inhibitor (PSI). Here the dose- and time-dependent sensitivity were mainly confined to cells with an epithelioid morphology. Selenite and proteasome inhibitors are potentially new contributions for the treatment of MM.
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| 8. |
- Yang, Yunlong, et al.
(författare)
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Anti-VEGF- and anti-VEGF receptor-induced vascular alteration in mouse healthy tissues
- 2013
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 110:29, s. 12018-12023
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Tidskriftsartikel (refereegranskat)abstract
- Systemic therapy with anti-VEGF drugs such as bevacizumab is widely used for treatment of human patients with various solid tumors. However, systemic impacts of such drugs in host healthy vasculatures remain poorly understood. Here, we show that, in mice, systemic delivery of an anti-VEGF or an anti-VEGF receptor (VEGFR)-2 neutralizing antibody caused global vascular regression. Among all examined tissues, vasculatures in endocrine glands, intestinal villi, and uterus are the most affected in response to VEGF or VEGFR-2 blockades. Thyroid vascular fenestrations were virtually completely blocked by VEGF blockade, leading to marked accumulation of intraendothelial caveolae vesicles. VEGF blockade markedly increased thyroid endothelial cell apoptosis, and withdrawal of anti-VEGF resulted in full recovery of vascular density and architecture after 14 d. Prolonged anti-VEGF treatment resulted in a significant decrease of the circulating level of the predominant thyroid hormone free thyroxine, but not the minimal isoform of triiodothyronine, suggesting that chronic anti-VEGF treatment impairs thyroid functions. Conversely, VEGFR-1-specific blockade produced virtually no obvious phenotypes. These findings provide structural and functional bases of anti-VEGF-specific drug-induced side effects in relation to vascular changes in healthy tissues. Understanding anti-VEGF drug-induced vascular alterations in healthy tissues is crucial to minimize and even to avoid adverse effects produced by currently used anti-VEGF-specific drugs.
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