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Find video protocols related to scientific articles indexed in Pubmed.
Activation of CD1d-restricted natural killer T cells can inhibit cancer cell proliferation during chemotherapy by promoting the immune responses in murine mesothelioma.
Cancer Immunol. Immunother.
PUBLISHED: 09-03-2014
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We studied the impact of natural killer T (NKT) cell activation by alpha-galactocysylceramide (?-GalCer, ?-GC) on cancer cell repopulation during chemotherapy in murine mesothelioma. The number of NKT cells was found to be increased during the development of murine mesothelioma. NKT cells specifically recognize ?-GC through CD1d resulting in their activation and expansion. Tumor-bearing mice were treated with chemotherapy once weekly, and ?-GC was followed after each cycle of chemotherapy. Anti-tumor effect was evaluated on wild-type (WT) and CD1d knockout (CD1dKO) mice. Cancer cell proliferation and apoptosis were evaluated by Ki67 and TUNEL immunohistochemistry. CD4(+) and CD8(+) T cell proportion and activation in tumor, spleen, draining lymph node and peripheral blood were determined by flow cytometry, and gene expression of activated T cell-related cytokines was quantified by reverse transcription PCR. NKT cells were identified by CD1d-?-GC-tetramer staining. In WT mice, tumor growth delay was achieved by cisplatin (Cis), and this effect was improved in combination with ?-GC, but ?-GC alone had little effect. Cancer cell proliferation during chemotherapy was significantly inhibited by ?-GC, while cancer cell death was significantly upregulated. ?-GC following chemotherapy resulted in NKT cell expansion and an increase of interferon-? production in the draining lymph node, blood and spleen. Gene expression of immune-associated cytokines was upregulated. Strikingly, the percentage of inducible T cell co-stimulator(+)CD4 T cells, Th17/Tc17 cells increased in splenocytes. In CD1d KO mice, however, Cis alone was less effective and Cis + ?-GC provided no additional benefit over Cis alone. ?-GC alone had minimal effect in both mice. NKT activation between cycles of chemotherapy could improve the outcome of mesothelioma treatment.
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Hetero-tri-spin [2p-3d-4f] chain compounds based on nitronyl nitroxide lanthanide metallo-ligands: synthesis, structure, and magnetic properties.
Chemistry
PUBLISHED: 08-28-2014
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Employing nitronyl nitroxide lanthanide(III) complexes as metallo-ligands allowed the efficient and highly selective preparation of three series of unprecedented hetero-tri-spin (Cu-Ln-radical) one-dimensional compounds. These 2p-3d-4f spin systems, namely [Ln3Cu(hfac)11(NitPhOAll)4] (Ln(III) = Gd 1Gd, Tb 1Tb, Dy 1Dy; NitPhOAll = 2-(4'-allyloxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide), [Ln3Cu(hfac)11(NitPhOPr)4] (Ln(III) = Gd 2Gd, Tb 2Tb, Dy 2Dy, Ho 2Ho, Yb 2Yb; NitPhOPr = 2-(4'-propoxyphenyl)-4,4,5,5-tetramethyl-imidazoline-1-oxyl-3-oxide) and [Ln3Cu(hfac)11(NitPhOBz)4] (Ln(III) = Gd 3Gd, Tb 3Tb, Dy 3Dy; NitPhOBz=2-(4'-benzyloxyphenyl)-4,4,5,5-tetramethyl-imidazoline-1-oxyl-3-oxide) involve O-bound nitronyl nitroxide radicals as bridging ligands in chain structures with a [Cu-Nit-Ln-Nit-Ln-Nit-Ln-Nit] repeating unit. The dc magnetic studies show that ferromagnetic metal-radical interactions take place in these hetero-tri-spin chain complexes, these and the next-neighbor interactions have been quantified for the Gd derivatives. Complexes 1Tb and 2Tb exhibit frequency dependence of ac magnetic susceptibilities, indicating single-chain magnet behavior.
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De novo synthesize of bile acids in pulmonary arterial hypertension lung.
Metabolomics
PUBLISHED: 03-26-2014
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Although multiple, complex molecular studies have been done for understanding the development and progression of pulmonary hypertension (PAH), little is known about the metabolic heterogeneity of PAH. Using a combination of high-throughput liquid-and-gas-chromatography-based mass spectrometry, we found bile acid metabolites, which are normally product derivatives of the liver and gallbladder, were highly increased in the PAH lung. Microarray showed that the gene encoding cytochrome P450 7B1 (CYP7B1), an isozyme for bile acid synthesis, was highly expressed in the PAH lung compared with the control. CYP7B1 protein was found to be primarily localized on pulmonary vascular endothelial cells suggesting de novo bile acid synthesis may be involved in the development of PAH. Here, by profiling the metabolomic heterogeneity of the PAH lung, we reveal a newly discovered pathogenesis mechanism of PAH.
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Antitumor effect of a selective COX-2 inhibitor, celecoxib, may be attributed to angiogenesis inhibition through modulating the PTEN/PI3K/Akt/HIF-1 pathway in an H?? murine hepatocarcinoma model.
Oncol. Rep.
PUBLISHED: 02-04-2014
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Celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, has recently been shown to affect the development of different types of cancer. The present study utilized a murine H22 hepatocarcinoma model to investigate the molecular mechanisms involved in celecoxib-induced inhibition of tumor angiogenesis. Tumor-bearing mice were randomly divided into five groups: i) control; ii) low-dose celecoxib (50 mg/kg); iii) high-dose celecoxib (200 mg/kg); iv) 5-fluorouracil (5-FU), (20 mg/kg) and v) combination of 5-FU and celecoxib (50 mg/kg). The antitumor effect of celecoxib was determined by measuring tumor volume. Tumor angiogenesis was evaluated by microvessel density (MVD). Tumor histology and immunostaining for CD34 in endothelial cells were performed to detect MVD. The expression levels of phosphatase and tensin homologue deleted from chromosome 10 (PTEN), phosphatidylinositol 3-kinase (PI3K), phospho?Akt (P-Akt), COX-2, hypoxia-inducible factor-1? (HIF-1?) and vascular endothelial growth factor-A (VEGF-A) were detected by ELISA, immunohistochemistry and western blotting, respectively. We discovered substantial growth delay in murine H22 hepatoma as a result of celecoxib treatment. The inhibition rate of tumor growth induced by high-dose and low-dose celecoxib was 49.3 and 37.0%, respectively (P<0.05). The expression of PI3K, P-Akt, COX-2, HIF-1?, VEGF-A and PTEN in tumor tissues treated with celecoxib was demonstrated by immunohistochemistry, and the MVD was decreased in a dose-dependent manner (P<0.05). Reduced PI3K and P-Akt was particularly apparent in the high-dose celecoxib group (P<0.05). ELISA and western blotting data showed that the expression of PI3K, P-Akt, COX-2, HIF-1? and VEGF-A were reduced and PTEN was increased after treatment with celecoxib. In conclusion, the impact of celecoxib-induced tumor growth delay of murine H22 hepatocarcinoma may correlate with the inhibition of angiogenesis by reducing PI3K, P-Akt, COX-2, HIF-1? and VEGF-A expression and increasing PTEN expression in tumor tissue.
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Nitronyl nitroxide-metal complexes as metallo-ligands for the construction of hetero-tri-spin (2p-3d-4f) chains.
Chem. Commun. (Camb.)
PUBLISHED: 01-09-2014
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A novel approach for the preparation of hetero-tri-spin magnetic compounds is described. It consists in using preformed metal-nitronyl nitroxide complexes as metallo-ligands in an assembling process involving an additional metal centre. This is illustrated by two unprecedented radical-Cu-Ln chain compounds (Ln = Gd(3+), Tb(3+)).
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Metabolomic heterogeneity of pulmonary arterial hypertension.
PLoS ONE
PUBLISHED: 01-01-2014
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Although multiple gene and protein expression have been extensively profiled in human pulmonary arterial hypertension (PAH), the mechanism for the development and progression of pulmonary hypertension remains elusive. Analysis of the global metabolomic heterogeneity within the pulmonary vascular system leads to a better understanding of disease progression. Using a combination of high-throughput liquid-and-gas-chromatography-based mass spectrometry, we showed unbiased metabolomic profiles of disrupted glycolysis, increased TCA cycle, and fatty acid metabolites with altered oxidation pathways in the human PAH lung. The results suggest that PAH has specific metabolic pathways contributing to increased ATP synthesis for the vascular remodeling process in severe pulmonary hypertension. These identified metabolites may serve as potential biomarkers for the diagnosis of PAH. By profiling metabolomic alterations of the PAH lung, we reveal new pathogenic mechanisms of PAH, opening an avenue of exploration for therapeutics that target metabolic pathway alterations in the progression of PAH.
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Liquid crystalline phase behavior and sol-gel transition in aqueous halloysite nanotube dispersions.
Langmuir
PUBLISHED: 09-26-2013
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The liquid crystalline phase behavior and sol-gel transition in halloysite nanotubes (HNTs) aqueous dispersions have been investigated by applying polarized optical microscopy (POM), macroscopic observation, rheometer, small-angle X-ray scattering, scanning electron microscopy, and transmission electron microscopy. The liquid crystalline phase starts to form at the HNT concentration of 1 wt %, and a full liquid crystalline phase forms at the HNT concentration of 25 wt % as observed by POM and macroscopic observation. Rheological measurements indicate a typical shear flow behavior for the HNT aqueous dispersions with concentrations above 20 wt % and further confirm that the sol-gel transition occurs at the HNT concentration of 37 wt %. Furthermore, the HNT aqueous dispersions exhibit pH-induced gelation with more intense birefringence when hydrochloric acid (HCl) is added. The above findings shed light on the phase behaviors of diversely topological HNTs and lay the foundation for fabrication of the long-range ordered nano-objects.
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Antitumor impact of interferon-? producing CD1d-restricted NKT cells in murine malignant mesothelioma.
J. Immunother.
PUBLISHED: 09-03-2013
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CD1d-restricted natural killer T (iNKT) cells have been shown to provide adjuvant activity against cancer by producing interferon (IFN)-?. However, the role of invariant NKT (iNKT) cells in the tumor microenvironment has not yet been fully addressed. Our aim is to elucidate the antitumor effect of iNKT cells in the tumor microenvironment by using an intrathoracic murine malignant pleural mesothelioma model that we had previously developed and to provide pleural effusion as a good surrogate of the tumor microenvironment. We found that the number of iNKT cells increased dramatically in the pleural effusion after intrathoracic tumor cell injection at an earlier phase compared with accumulation of CD8 T cells. These iNKT cells showed increased expression of CD25 and increased ratio of cells positive for IFN-? intracellular staining. iNKT cells sorted from pleural effusion of tumor burden mice produced larger amount of IFN-? compared with naive mice. Mice pretreated in vivo with anti-CD1d-blocking Ab showed increased amount of pleural effusion and decreased ratio of total and effector-type CD8 T cells as well as decreased intracellular IFN-? expression of CD8T-cell in the pleural effusion. In vivo administration of ?-galactosylceramide (?-GalCer) showed prolonged survival associated with less pleural effusion and increased ratio of IFN-?-positive iNKT cells and CD8 T cells in the pleural effusion. Therefore, this study suggests that iNKT cells accumulating in the tumor microenvironment play an antitumor effect by producing IFN-? and enhancing subsequent CD8 T-cell response. Furthermore, in vivo administration of ?-GalCer could suppress mesothelioma growth by activating iNKT cells.
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Impact of acetylsalicylic acid on tumor angiogenesis and lymphangiogenesis through inhibition of VEGF signaling in a murine sarcoma model.
Oncol. Rep.
PUBLISHED: 01-14-2013
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Aspirin is a salicylate drug that is widely used, and recently it has been shown to influence the development of various types of cancers. Our previous study revealed that aspirin had an inhibitory effect on the growth of S180 sarcoma and 3AO human ovarian cancer cells. The present study utilized a murine S180 sarcoma model to investigate the molecular mechanisms involved in aspirin-induced tumor growth inhibition. Tumor-bearing mice were randomly divided into five groups with 10 mice in each group: i) control; ii) 5-fluorouracil (5-FU); iii) high-dose aspirin (250 mg/kg); iv) low-dose aspirin (50 mg/kg); and v) combination of 5-FU and aspirin (50 mg/kg). The effect of aspirin on tumor growth was observed by measuring tumor volume and evaluating the antitumor effect. Tumor histology and immunohistochemistry were performed to detect the microvessel density (MVD), lymphatic vessel density (LVD), and the expression levels of vascular endothelial growth factor A (VEGF-A) and VEGF-C. The expression of VEGF-A and VEGF-C was also confirmed and quantified by western blotting. We discovered significant growth delay in murine S180 sarcoma as a result of aspirin treatment. The inhibition rate of tumor growth induced by high-dose and low-dose aspirin was 33.5 and 22.2%, respectively (P<0.05). The expression of VEGF-A and VEGF-C in tumor tissues inhibited by aspirin was demonstrated by immunohistochemistry, and the MVD was decreased in a dose-dependent manner (p<0.05). Reduced LVD was particularly apparent in the high-dose aspirin group (p<0.05). Western blot data showed that the expression of both VEGF-A and VEGF-C was reduced after treatment with aspirin. In conclusion, the impact of aspirin-induced tumor growth delay of murine S180 sarcoma may correlate with the inhibition of angiogenesis and lymphangiogenesis by reducing VEGF-A and VEGF-C expression in tumor tissues.
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[Effect of polypeptide extract from scorpion venom (PESV) on expression of HIF-1alpha and SDF-1/CXCR4 in repopulating H22 tumour tissue during chemotherapy treatment].
Zhongguo Zhong Yao Za Zhi
PUBLISHED: 10-29-2011
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To study the expression of HIF-1alpha and SDF-1/CXCR4 in repopulating H22 tumor tissue and the mechanism of angiogenesis of polypeptide extract from scorpion venom (PESV) during chemotherapy treatment.
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Tumor cell repopulation between cycles of chemotherapy is inhibited by regulatory T-cell depletion in a murine mesothelioma model.
J Thorac Oncol
PUBLISHED: 06-07-2011
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Malignant pleural mesothelioma is a highly aggressive cancer with poor prognosis. We have previously demonstrated that regulatory T cells (Treg) depletion can impact tumor microenvironment when combined with chemotherapy. The aim of this study is to analyze the impact of Treg depletion on tumor cell repopulation during cycles of chemotherapy in a murine mesothelioma model.
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Synergistic antitumor effects of regulatory T cell blockade combined with pemetrexed in murine malignant mesothelioma.
J. Immunol.
PUBLISHED: 06-14-2010
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CD4(+)CD25(+) regulatory T cells (Tregs) can promote the growth of some tumors, but it is unknown whether this is true for all tumors, including malignant pleural mesothelioma. We have previously shown that the existence of Tregs was associated with poor survival in patients with malignant pleural mesothelioma. In this study, using an intrathoracic murine model of malignant mesothelioma (MM), we provide evidence suggesting that Treg blockade could enhance survival when combined with pemetrexed in established tumor. AC29 murine MM cells were injected into the right pleural cavity of CBA mice for tumor development. Four days after the tumor injection, tumor-bearing mice were then treated with pemetrexed alone, Treg blockade alone, or a combination of pemetrexed and Treg blockade. We observed a synergistic antitumor effect of Treg blockade combined with pemetrexed resulting in prolonged survival. The combination of Treg blockade and pemetrexed was associated with decreased tumor-infiltrating Tregs, increased IL-2 production, dendritic cell maturation, and increased CD3(+)CD8(+)IFN-gamma(+) tumor-infiltrating T cells when compared with mice treated with pemetrexed alone or Treg blockade alone. The survival benefit was abrogated if anti-CD8 mAb was administered simultaneously. Likewise, the survival benefit resulting from the combined Treg blockade with pemetrexed was not observed when immunodeficient mice were used. Therefore, this study suggests that Treg blockade combined with pemetrexed can suppress mesothelioma growth in established tumor in vivo through an immune-mediated process. This study also validates a new intrathoracic tumor model of pleural effusion to explore the role of antitumor immunity in murine MM.
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[Preliminary study of metabonomcs on aqueous extract of Evodia rutaecarpa in sprague-dawley rats].
Zhongguo Zhong Yao Za Zhi
PUBLISHED: 03-31-2010
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To study the change of endogenous metabolites of SD rats administrated of aqueous extract of Evodiae rutaecarpa.
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Smooth transition between SMM and SCM-type slow relaxing dynamics for a 1-D assemblage of {Dy(nitronyl nitroxide)2} units.
Chem. Commun. (Camb.)
PUBLISHED: 03-12-2010
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A model example for size effects on the dynamic susceptibility behavior is provided by the chain compound [{Dy(hfac)(3)NitPhIm(2)}Dy(hfac)(3)] (NitPhIm = 2-[4-(1-imidazole)phenyl]nitronyl nitroxide radical). The Arrhenius plot reveals two relaxation regimes attributed to SMM (Delta = 17.1 K and tau(0) = 17.5 x 10(-6) s) and SCM (Delta = 82.7 K and tau(0) = 8.8 x 10(-8) s) behaviors. The ferromagnetic exchange among the spin carriers has been established for the corresponding Gd derivative.
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Dynamic magnetic behavior and magnetic ordering in one-dimensional Tb-nitronyl nitroxide radical chain.
Dalton Trans
PUBLISHED: 02-17-2010
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A new nitronyl nitroxide bridged one-dimensional lanthanide complex [Tb(3)(hfac)(9)(NIT-2thien)(3)](n) (1) (NIT-2thien = 2-(2-thienyl)-4,4,5,5-tetramethyl-imidazoline-1-oxyl-3-oxide) has been successfully prepared. Single crystal X-ray crystallographic analysis reveals that complex 1 consists of linear chains built up by Tb(hfac)(3) units bridged by NIT-2thien radicals through their NO groups; the chains run along the crystallographic a-axis. The magnetic behavior of complex 1 is quite unusual. The complex shows the concomitant existence of slow magnetic relaxation and three-dimensional magnetic ordering.
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Concurrent and sequential administration of chemotherapy and the Mammalian target of rapamycin inhibitor temsirolimus in human cancer cells and xenografts.
Clin. Cancer Res.
PUBLISHED: 08-25-2009
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Optimal scheduling of cycle-active chemotherapy with (initially cytostatic) molecular-targeted agents is important to maximize clinical benefit. Concurrent scheduling might allow up-regulation of cell death pathways at the time of chemotherapy, whereas sequential treatments might maximize inhibition of repopulation and avoid putting tumor cells out of cycle when administering cycle-active chemotherapy. We compared the effects of concurrent and sequential administration of chemotherapy and the mammalian target of rapamycin (mTOR) inhibitor temsirolimus (CCI-779) on tumor cells and xenografts.
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Single-molecule magnets based on rare earth complexes with chelating benzimidazole-substituted nitronyl nitroxide radicals.
Dalton Trans
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Three rare earth-nitronyl nitroxide radical complexes [Ln(tfa)(3)(NIT-BzImH)] (Ln(III) = Gd 1, Tb 2, Dy 3; tfa = trifluoroacetylacetonate; NIT-BzImH = 2-(2-benzimidazolyl)-4,4,5,5-tetramethylimidazolyl-1-oxyl-3-oxide) have been successfully prepared and structurally characterized. X-Ray crystallographic analysis reveals that all three complexes are isomorphous. Their crystal structures consist of mononuclear molecule units in which lanthanide(III) is 8-coordinated to one NIT-BzImH and three trifluoroacetylacetonate ligands. The NIT-BzImH acts as a bidentate ligand via its nitrogen atom of the imidazole ring and the oxygen atom of the N-O group. The magnetic properties of complexes 1-3 were studied. All the three complexes exhibit ferromagnetic Ln(III)-radical coupling. AC magnetic susceptibility studies of 2 and 3 show slow magnetic relaxation suggesting that they behave as SMMs.
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Ligand substitution effect on single-molecule magnet behavior in dinuclear dysprosium complexes with radical functionalized phenol as bridging ligands.
Dalton Trans
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Reaction of Dy(hfac)(3)·2H(2)O (hfac = hexafluoroacetyl acetonate) with 2-(2-hydroxyphenyl)nitronyl nitroxide (NITPhOH) and 2-(5-bromo-2-hydroxyphenyl)nitronyl nitroxide (NIT5BrPhOH) yielded [Dy(2)(hfac)(4)(NITPhO)(2)] 1 and [Dy(2)(hfac)(4)(NIT5BrPhO)(2)] 2, respectively. These compounds are phenoxo-O bridged binuclear complexes with the radical unit of a ligand coordinated to a single Dy. The Ln centers exhibit a heptacoordinated environment. Despite having very similar structures, these compounds exhibit distinct magnetic behaviors. Compound 1 shows slow relaxation of its magnetization indicating single-molecule magnet behavior, while no frequency-dependent out-of-phase signals were found for complex 2. This difference is likely to result from electronic effects induced by halogen substitution.
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CTLA-4 blockade expands infiltrating T cells and inhibits cancer cell repopulation during the intervals of chemotherapy in murine mesothelioma.
Mol. Cancer Ther.
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Cancer immunotherapy has shown promising results when combined with chemotherapy. Blocking CTLA-4 signaling by monoclonal antibody between cycles of chemotherapy may inhibit cancer cell repopulation and enhance the antitumoral immune reaction, thus improve the efficacy of chemotherapy in mesothelioma. The impact of CTLA-4 blockade on the early stage of tumor development was evaluated in a subcutaneous murine mesothelioma model. CTLA-4 blocking antibody was administered following each cycle of chemotherapy, and monotherapy was included as controls. Antitumor effect was evaluated by tumor growth delay and survival of the animals. Tumor cell repopulation was quantified by bromodeoxyuridine incorporation and Ki67 by immunohistochemistry and/or flow cytometry. In vitro cell killing was determined by classic chromium-released assay, and reverse transcription PCR (RT-PCR) was carried out to determine the gene expression of associated cytokines. Anti-CTLA-4 monoclonal antibody was able to inhibit tumor growth at early stage of tumor development. Antitumor effect was achieved by administration of CTLA-4 blockade between cycles of chemotherapy. Tumor cell repopulation during the intervals of cisplatin was inhibited by CTLA-4 blockade. Anti-CTLA-4 therapy gave rise to an increased number of CD4 and CD8 T cells infiltrating the tumor. RT-PCR showed that the gene expression of interleukin IL-2, IFN-?, granzyme B, and perforin increased in the tumor milieu. Blockade of CTLA-4 signaling showed effective anticancer effect, correlating with inhibiting cancer cell repopulation between cycles of chemotherapy and upregulating tumor-infiltrating T lymphocytes, cytokines, and cytolytic enzymes in a murine mesothelioma model.
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A new family of Ln-radical chains (Ln = Nd, Sm, Gd, Tb and Dy): synthesis, structure, and magnetic properties.
Dalton Trans
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Five new one-dimensional rare earth-nitronyl nitroxide radical complexes [Ln(hfac)3(NIT-3BrPhOMe)]n (Ln = Nd (), Sm (), Gd (), Tb (), Dy (); hfac = hexafluoroacetylacetonate; NIT-3BrPhOMe = 2-(3-bromo-4-methoxyl)-4,4,5,5-tetramethyl-imidazolyl-1-oxyl-3-oxide) have been successfully prepared and structurally characterized. Five complexes possess linear chain structure in which the NIT-3BrPhOMe radical ligands link Ln(hfac)3 units through the oxygen atoms of nitronyl nitroxide groups. DC magnetic studies show that Nd, Sm and Gd complexes are paramagnetic above 2.0 K, whereas Tb and Dy complexes show antiferromagnetic ordering with TN = 19.9 K and 6.4 K, respectively. Moreover, Tb and Dy complexes exhibit frequency-dependence of ac magnetic susceptibilities, suggesting the presence of slow magnetic relaxation. This work demonstrated that the substituents of the nitronyl nitroxide radical and the lanthanide ion can play a crucial role in modulating the magnetic behavior for one-dimensional lanthanide-radical systems.
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