AIM:To investigate serum PC-594 fatty acid levels as a potential biomarker in North American pancreatic cancer(PaC) patients,and to compare its performance to CA19-9.METHODS:Using tandem mass spectrometry,we evaluated...AIM:To investigate serum PC-594 fatty acid levels as a potential biomarker in North American pancreatic cancer(PaC) patients,and to compare its performance to CA19-9.METHODS:Using tandem mass spectrometry,we evaluated serum PC-594 levels from 84 North American patients with confirmed PaC and 99 cancer-free control subjects.We determined CA19-9 levels by ELISA.Significance between Pa C patients and controls,and association with clinical variables was determined by analysis of variance and t-tests.Diagnostic performance was evaluated by receiver-operator characteristic(ROC)curve analysis,and PC-594 correlation with age and CA19-9 determined by regression analysis.RESULTS:Mean PC-594 levels were 3.7 times lower in Pa C patients compared to controls(P < 0.0001).The mean level in PaC patient serum was 0.76 ± 0.07 μmol/L,and the mean level in control subjects was 2.79 ± 0.15 μmol/L.There was no correlation between PC-594 and age,disease stage or gender(P > 0.05).Using 1.25 μmol/L as a PC-594 threshold produced a relative risk(RR) of 9.4(P < 0.0001,95%CI:5.0-17.7).The area under the receiver-operator characteristic curve(ROCAUC) was 0.93(95%CI:0.91-0.95) for PC-594 and 0.85(95%CI:0.82-0.88) for CA19-9.Sensitivity at 90% specificity was 87% for PC-594 and 71% for CA19-9.Six Pa C patients with CA19-9 above 35 U/m L showed normal PC-594 levels,while 24 Pa C patients with normal CA19-9 showed low PC-594 levels.Eighty-five of the 99 control subjects(86%) showed normal levels of both markers.CONCLUSION:PC-594 biomarker levels are significantly reduced in North American Pa C patients,and showed superior diagnostic performance compared to CA19-9.展开更多
Chronic inflammation induced hyper-proliferation, and migration of keratinocytes are pathological hallmarks of psoriasis. Extracts from Sphaeranthus spp. demonstrate pharmacological activity in-vitro and in-vivo. Howe...Chronic inflammation induced hyper-proliferation, and migration of keratinocytes are pathological hallmarks of psoriasis. Extracts from Sphaeranthus spp. demonstrate pharmacological activity in-vitro and in-vivo. However, the activity in modulating disease relevant pathways in psoriasis has not been reported. In the current study, a standardized herbal extract from Sphaeranthus indicus (NPS31807) was used to study the mechanistic activity under conditions of inflammation, keratinocyte proliferation and migration using cell based and gene expression assays. NPS31807 treatment reduced levels of pro-inflammatory cytokines from human macrophages and activated epidermal keratinocytes in a dose dependent manner. Treatment with NPS31807 diminished NFκB and AP-1 transcription activity in human macrophages. Lowered nuclear translocation of p65 sub-unit in macrophages by treatment confirmed reduced activity of NFκB. Gene expression profiling showed attenuated expression of genes involved with inflammation such as TNF signaling, and angiogenesis by NPS31807. Inhibition of angiogenesis and matrix metalloproteinase production in keratinocytes was confirmed using RTq-PCR assays. Pretreatment with NPS31807 led to significant reduction of STAT3 phosphorylation and mitogen induced cellular migration. NPS31807 induced inhibition of proliferative genes and BrdU uptake in epidermal keratinocytes. In summary, our study provides novel molecular insights into the anti-inflammatory, anti-migratory and anti-proliferative properties of NPS31807. In summary, NPS31807, an extract from Sphaeranthus indicus can be used as therapeutic option in inflammatory and auto-immune conditions such as psoriasis.展开更多
文摘AIM:To investigate serum PC-594 fatty acid levels as a potential biomarker in North American pancreatic cancer(PaC) patients,and to compare its performance to CA19-9.METHODS:Using tandem mass spectrometry,we evaluated serum PC-594 levels from 84 North American patients with confirmed PaC and 99 cancer-free control subjects.We determined CA19-9 levels by ELISA.Significance between Pa C patients and controls,and association with clinical variables was determined by analysis of variance and t-tests.Diagnostic performance was evaluated by receiver-operator characteristic(ROC)curve analysis,and PC-594 correlation with age and CA19-9 determined by regression analysis.RESULTS:Mean PC-594 levels were 3.7 times lower in Pa C patients compared to controls(P < 0.0001).The mean level in PaC patient serum was 0.76 ± 0.07 μmol/L,and the mean level in control subjects was 2.79 ± 0.15 μmol/L.There was no correlation between PC-594 and age,disease stage or gender(P > 0.05).Using 1.25 μmol/L as a PC-594 threshold produced a relative risk(RR) of 9.4(P < 0.0001,95%CI:5.0-17.7).The area under the receiver-operator characteristic curve(ROCAUC) was 0.93(95%CI:0.91-0.95) for PC-594 and 0.85(95%CI:0.82-0.88) for CA19-9.Sensitivity at 90% specificity was 87% for PC-594 and 71% for CA19-9.Six Pa C patients with CA19-9 above 35 U/m L showed normal PC-594 levels,while 24 Pa C patients with normal CA19-9 showed low PC-594 levels.Eighty-five of the 99 control subjects(86%) showed normal levels of both markers.CONCLUSION:PC-594 biomarker levels are significantly reduced in North American Pa C patients,and showed superior diagnostic performance compared to CA19-9.
文摘Chronic inflammation induced hyper-proliferation, and migration of keratinocytes are pathological hallmarks of psoriasis. Extracts from Sphaeranthus spp. demonstrate pharmacological activity in-vitro and in-vivo. However, the activity in modulating disease relevant pathways in psoriasis has not been reported. In the current study, a standardized herbal extract from Sphaeranthus indicus (NPS31807) was used to study the mechanistic activity under conditions of inflammation, keratinocyte proliferation and migration using cell based and gene expression assays. NPS31807 treatment reduced levels of pro-inflammatory cytokines from human macrophages and activated epidermal keratinocytes in a dose dependent manner. Treatment with NPS31807 diminished NFκB and AP-1 transcription activity in human macrophages. Lowered nuclear translocation of p65 sub-unit in macrophages by treatment confirmed reduced activity of NFκB. Gene expression profiling showed attenuated expression of genes involved with inflammation such as TNF signaling, and angiogenesis by NPS31807. Inhibition of angiogenesis and matrix metalloproteinase production in keratinocytes was confirmed using RTq-PCR assays. Pretreatment with NPS31807 led to significant reduction of STAT3 phosphorylation and mitogen induced cellular migration. NPS31807 induced inhibition of proliferative genes and BrdU uptake in epidermal keratinocytes. In summary, our study provides novel molecular insights into the anti-inflammatory, anti-migratory and anti-proliferative properties of NPS31807. In summary, NPS31807, an extract from Sphaeranthus indicus can be used as therapeutic option in inflammatory and auto-immune conditions such as psoriasis.