Summary： The specific anti-tumor immune response induced by mouse bone marrow dendritic cells （DCs） lransfected with recombinant adenovirus carrying mutant k-ras genes was investighted. DCs were generated from mous...Summary： The specific anti-tumor immune response induced by mouse bone marrow dendritic cells （DCs） lransfected with recombinant adenovirus carrying mutant k-ras genes was investighted. DCs were generated from mouse bone marrow in the presence of rmGM-CSF （3.3 ng/mL） and rmIL-4 （1.3 ng/mL） and detected by FACS, and then transfecled with the recombinant adenovirus encoding mutant k ras gene. The efficacy of transfection and T cell stimulating activity of DCs were detected. CTL activity of the mice vaccinated with DCs was observed. The resuhs showed thai DCs had dendritic veiled morphology. BmDCs highly expressed B7-1（80%）, B7-2（77%）, MHC Ⅱ （70%）, CDllc （65%）, CD40 （70%） and CD54 （96%） with FACS, and no significant difference in the expression was observed before and after the transfection （P〈0.05）. The DCs transfeeled by mutant k-ras gene could significantly stimulate lymphoeytes proliferation as compared with those transfeeted by Ad e or non-modified DCs （P〈0.05）. DC vaccine transfected by mutant k-ras gene could induce CTL activity against Lewis lung cancer, but not against B16. The specific eytotoxicity against Lewis lung cancer in Ad-k-ras/12-transdueed DC group was signifieantly higher than those in the control, vector and non transfeeted DCs groups （P〈0.05）. It was concluded that special antitumor response could be induced by DCs transfected with recombinant adenovirus carrying mutant k-ras genes.展开更多
The manganese deposit of North Téra is located in the western side of the Diagorou-Darbani greenstone belt in the Niger Liptako Province(Northeastern part of Man Schield,West African Craton).Manganese mineralizat...The manganese deposit of North Téra is located in the western side of the Diagorou-Darbani greenstone belt in the Niger Liptako Province(Northeastern part of Man Schield,West African Craton).Manganese mineralization bearing rocks are mainly gondites(a kind of garnet-rich quartzite of the spessartine type)whose borders consist of a high concentration of Mn oxide concretions.The methodological approach implemented consisted of a field study followed by a polarizing microscopic analysis in transmitted and reflected light and a geochimical analysis.North Téra gondites originate from Birimian manganese-rich sediments metamorphism in amphibolite facies.The supergene alteration,more or less important,has developed on the protore of gondites,a saprolitic profile whose setting up conditions were recently described in our previous work.The macroscopic analysis of the manganese deposits samples combined with the metallographic microscopic and geochemical analysis confirms that manganese mineralization originated from weathering processes.The first oxide that forms around the garnets is nsutite,while the mesostasis is invaded by pyrolusite with lenses of lithiophorite destabilizing in favor of pyrolusite.In the botryoidal concretions,the latter forms an alternation with the psilomelane rich in Ba(8,101ppm)in the uppermost levels.The abundance diagram shows that the normalize Rare Earths compared to PAAS derived from a plagioclase-rich quartzitic source.This observation is corroborated by a positive anomaly in Eu.Otherwise,the high levels of transition elements(Ni,V,Co and Cr)highlight the involvement of a basic source.The contents of major elements show a significant leaching,with an increase in those of Mn and Al during the increasing weathering.The CIA and PIA indices move in the same direction towards high values leading to the Al2O3 pole on the Al2O3-CaO*+Na2O-K2O diagram.This indicates an increasing alteration along the profile,according to an alteration path comprising plagioclase-smectite-kaolinite and illite to kaolinite.展开更多
AIM:To investigate the prognostic role of invariant natural killer T(iNKT) cells and antibody-dependent cell-mediated cytotoxicity(ADCC) in wild type KRAS metastatic colorectal cancer(mC RC) patients treated with cetu...AIM:To investigate the prognostic role of invariant natural killer T(iNKT) cells and antibody-dependent cell-mediated cytotoxicity(ADCC) in wild type KRAS metastatic colorectal cancer(mC RC) patients treated with cetuximab.METHODS: Forty-one KRAS wt mC RC patients,treated with cetuximab and irinotecan-based chemotherapy in Ⅱ and Ⅲ lines were analyzed. Genotyping of single nucleotide polymorphism(SNP)s in the FCGR2A,FCGR3A and in the 3' untranslated regions of KRAS and mutational analysis for KRAS,BRAF and NRAS genes was determined either by sequencing or allelic discrimination assays. Enriched NK cells were obtained from lymphoprepperipheral blood mononuclear cell and iN KT cells were defined by co-expression of CD3,TCRVα24,TCRVβ11. ADCC was evaluated as ex vivo NK-dependent activity,measuring lactate dehydrogenase release.RESULTS: At basal,mCRC patients performing ADCC activity above the median level(71%) showed an improved overall survival(OS) compared to patients with ADCC below(median 16 vs 8 mo;P=0.026). We did not find any significant correlation of iN KT cells with OS(P=0.19),albeit we observed a trend to a longer survival after 10 mo in patients with iN KT above median basal level(0.382 cells/microliter). Correlation of OS and progression-free survival(PFS) with interesting SNPs involved in ADCC ability revealed not to be significant. Patients carrying alleles both with A in FCGR2 A and TT in FCGR3A presented a trend of longer PFS(median 9 vs 5 mo;P=0.064). Chemotherapy impacted both iN KT cells and ADCC activity. Their prognostic values get lost when we analysed them after 2 and 4 mo of treatment.CONCLUSION: Our results suggest a link between iN KT cells,basal ADCC activity,genotypes in FCGR2A and FCGR3A,and efficacy of cetuximab in KRAS wt mC RC patients.展开更多
文摘Summary： The specific anti-tumor immune response induced by mouse bone marrow dendritic cells （DCs） lransfected with recombinant adenovirus carrying mutant k-ras genes was investighted. DCs were generated from mouse bone marrow in the presence of rmGM-CSF （3.3 ng/mL） and rmIL-4 （1.3 ng/mL） and detected by FACS, and then transfecled with the recombinant adenovirus encoding mutant k ras gene. The efficacy of transfection and T cell stimulating activity of DCs were detected. CTL activity of the mice vaccinated with DCs was observed. The resuhs showed thai DCs had dendritic veiled morphology. BmDCs highly expressed B7-1（80%）, B7-2（77%）, MHC Ⅱ （70%）, CDllc （65%）, CD40 （70%） and CD54 （96%） with FACS, and no significant difference in the expression was observed before and after the transfection （P〈0.05）. The DCs transfeeled by mutant k-ras gene could significantly stimulate lymphoeytes proliferation as compared with those transfeeted by Ad e or non-modified DCs （P〈0.05）. DC vaccine transfected by mutant k-ras gene could induce CTL activity against Lewis lung cancer, but not against B16. The specific eytotoxicity against Lewis lung cancer in Ad-k-ras/12-transdueed DC group was signifieantly higher than those in the control, vector and non transfeeted DCs groups （P〈0.05）. It was concluded that special antitumor response could be induced by DCs transfected with recombinant adenovirus carrying mutant k-ras genes.
文摘The manganese deposit of North Téra is located in the western side of the Diagorou-Darbani greenstone belt in the Niger Liptako Province(Northeastern part of Man Schield,West African Craton).Manganese mineralization bearing rocks are mainly gondites(a kind of garnet-rich quartzite of the spessartine type)whose borders consist of a high concentration of Mn oxide concretions.The methodological approach implemented consisted of a field study followed by a polarizing microscopic analysis in transmitted and reflected light and a geochimical analysis.North Téra gondites originate from Birimian manganese-rich sediments metamorphism in amphibolite facies.The supergene alteration,more or less important,has developed on the protore of gondites,a saprolitic profile whose setting up conditions were recently described in our previous work.The macroscopic analysis of the manganese deposits samples combined with the metallographic microscopic and geochemical analysis confirms that manganese mineralization originated from weathering processes.The first oxide that forms around the garnets is nsutite,while the mesostasis is invaded by pyrolusite with lenses of lithiophorite destabilizing in favor of pyrolusite.In the botryoidal concretions,the latter forms an alternation with the psilomelane rich in Ba(8,101ppm)in the uppermost levels.The abundance diagram shows that the normalize Rare Earths compared to PAAS derived from a plagioclase-rich quartzitic source.This observation is corroborated by a positive anomaly in Eu.Otherwise,the high levels of transition elements(Ni,V,Co and Cr)highlight the involvement of a basic source.The contents of major elements show a significant leaching,with an increase in those of Mn and Al during the increasing weathering.The CIA and PIA indices move in the same direction towards high values leading to the Al2O3 pole on the Al2O3-CaO*+Na2O-K2O diagram.This indicates an increasing alteration along the profile,according to an alteration path comprising plagioclase-smectite-kaolinite and illite to kaolinite.
基金the Fondazione Veronesi that granted Daniela Vivenza and Martino Monteverde with PostDoctoral Fellowship Veronesithe Fondazione Cassa Risparmio of Cuneo for partially supporting the study
文摘AIM:To investigate the prognostic role of invariant natural killer T(iNKT) cells and antibody-dependent cell-mediated cytotoxicity(ADCC) in wild type KRAS metastatic colorectal cancer(mC RC) patients treated with cetuximab.METHODS: Forty-one KRAS wt mC RC patients,treated with cetuximab and irinotecan-based chemotherapy in Ⅱ and Ⅲ lines were analyzed. Genotyping of single nucleotide polymorphism(SNP)s in the FCGR2A,FCGR3A and in the 3' untranslated regions of KRAS and mutational analysis for KRAS,BRAF and NRAS genes was determined either by sequencing or allelic discrimination assays. Enriched NK cells were obtained from lymphoprepperipheral blood mononuclear cell and iN KT cells were defined by co-expression of CD3,TCRVα24,TCRVβ11. ADCC was evaluated as ex vivo NK-dependent activity,measuring lactate dehydrogenase release.RESULTS: At basal,mCRC patients performing ADCC activity above the median level(71%) showed an improved overall survival(OS) compared to patients with ADCC below(median 16 vs 8 mo;P=0.026). We did not find any significant correlation of iN KT cells with OS(P=0.19),albeit we observed a trend to a longer survival after 10 mo in patients with iN KT above median basal level(0.382 cells/microliter). Correlation of OS and progression-free survival(PFS) with interesting SNPs involved in ADCC ability revealed not to be significant. Patients carrying alleles both with A in FCGR2 A and TT in FCGR3A presented a trend of longer PFS(median 9 vs 5 mo;P=0.064). Chemotherapy impacted both iN KT cells and ADCC activity. Their prognostic values get lost when we analysed them after 2 and 4 mo of treatment.CONCLUSION: Our results suggest a link between iN KT cells,basal ADCC activity,genotypes in FCGR2A and FCGR3A,and efficacy of cetuximab in KRAS wt mC RC patients.
