PubMed:22132131 / 106-2367 JSONTXT

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    Inflammaging

    {"project":"Inflammaging","denotations":[{"id":"T3","span":{"begin":7,"end":182},"obj":"Sentence"},{"id":"T4","span":{"begin":183,"end":405},"obj":"Sentence"},{"id":"T5","span":{"begin":406,"end":624},"obj":"Sentence"},{"id":"T6","span":{"begin":625,"end":739},"obj":"Sentence"},{"id":"T7","span":{"begin":740,"end":775},"obj":"Sentence"},{"id":"T8","span":{"begin":776,"end":927},"obj":"Sentence"},{"id":"T9","span":{"begin":928,"end":1066},"obj":"Sentence"},{"id":"T10","span":{"begin":1067,"end":1301},"obj":"Sentence"},{"id":"T11","span":{"begin":1302,"end":1475},"obj":"Sentence"},{"id":"T12","span":{"begin":1476,"end":1625},"obj":"Sentence"},{"id":"T13","span":{"begin":1626,"end":1735},"obj":"Sentence"},{"id":"T14","span":{"begin":1736,"end":1864},"obj":"Sentence"},{"id":"T15","span":{"begin":1865,"end":1955},"obj":"Sentence"},{"id":"T16","span":{"begin":1956,"end":2107},"obj":"Sentence"},{"id":"T3","span":{"begin":7,"end":182},"obj":"Sentence"},{"id":"T4","span":{"begin":183,"end":405},"obj":"Sentence"},{"id":"T5","span":{"begin":406,"end":624},"obj":"Sentence"},{"id":"T6","span":{"begin":625,"end":739},"obj":"Sentence"},{"id":"T7","span":{"begin":740,"end":775},"obj":"Sentence"},{"id":"T8","span":{"begin":776,"end":927},"obj":"Sentence"},{"id":"T9","span":{"begin":928,"end":1066},"obj":"Sentence"},{"id":"T10","span":{"begin":1067,"end":1301},"obj":"Sentence"},{"id":"T11","span":{"begin":1302,"end":1475},"obj":"Sentence"},{"id":"T12","span":{"begin":1476,"end":1625},"obj":"Sentence"},{"id":"T13","span":{"begin":1626,"end":1735},"obj":"Sentence"},{"id":"T14","span":{"begin":1736,"end":1864},"obj":"Sentence"},{"id":"T15","span":{"begin":1865,"end":1955},"obj":"Sentence"},{"id":"T16","span":{"begin":1956,"end":2107},"obj":"Sentence"}],"text":"ROUND: Pancreatic cancer is one of the most aggressive cancers, with tumor-induced myeloid-derived suppressor cells (MDSC) contributing to its pathogenesis and ineffective therapies. In response to cytokine/chemokine receptor activation, src homology 2 domain-containing inositol 5'-phosphatase-1 (SHIP-1) influences phosphatidylinositol-3-kinase (PI3K) signaling events, which regulate immunohomeostasis. We hypothesize that factors from murine pancreatic cancer cells cause the down-regulation of SHIP-1 expression, which may potentially contribute to MDSC expansion, and the suppression of CD8(+) T cell immune responses. Therefore, we sought to determine the role of SHIP-1 in solid tumor progression, such as murine pancreatic cancer.\nMETHODOLOGY AND PRINCIPAL FINDINGS: Immunocompetent C57BL/6 mice were inoculated with either murine Panc02 cells (tumor-bearing [TB] mice) or Phosphate Buffer Saline (PBS) (control mice). Cytometric Bead Array (CBA) analysis of supernatants of cultured Panc02 detected pro-inflammatory cytokines such as IL-6, IL-10 and MCP-1. TB mice showed a significant increase in serum levels of pro-inflammatory factors IL-6 and MCP-1 measured by CBA. qRT-PCR and Western blot analyses revealed the in vivo down-regulation of SHIP-1 expression in splenocytes from TB mice. Western blot analyses also detected reduced SHIP-1 activity, increased AKT-1 and BAD hyper-phosphorylation and up-regulation of BCL-2 expression in splenocytes from TB mice. In vitro, qRT-PCR and Western blot analyses detected reduced SHIP-1 mRNA and protein expression in control splenocytes co-cultured with Panc02 cells. Flow cytometry results showed significant expansion of MDSC in peripheral blood and splenocytes from TB mice. AutoMACS sorted TB MDSC exhibited hyper-phosphorylation of AKT-1 and over-expression of BCL-2 detected by western blot analysis. TB MDSC significantly suppressed antigen-specific CD8(+) T cell immune responses in vitro.\nCONCLUSION/SIGNIFICANCE: SHIP-1 may regulate immune development that impacts MDSC expansion and function, contributing to pancreatic tumor progression. Thus, SHIP-1 can be a potential therapeutic target to help restore immunohomeostasis and improve therapeutic responses in patients with pancreatic cancer"}

    PubmedHPO

    {"project":"PubmedHPO","denotations":[{"id":"T1","span":{"begin":7,"end":24},"obj":"HP_0002894"},{"id":"T2","span":{"begin":18,"end":24},"obj":"HP_0002664"},{"id":"T3","span":{"begin":44,"end":54},"obj":"HP_0000718"},{"id":"T4","span":{"begin":55,"end":62},"obj":"HP_0002664"},{"id":"T5","span":{"begin":69,"end":74},"obj":"HP_0002664"},{"id":"T6","span":{"begin":446,"end":463},"obj":"HP_0002894"},{"id":"T7","span":{"begin":457,"end":463},"obj":"HP_0002664"},{"id":"T8","span":{"begin":687,"end":692},"obj":"HP_0002664"},{"id":"T9","span":{"begin":721,"end":738},"obj":"HP_0002894"},{"id":"T10","span":{"begin":732,"end":738},"obj":"HP_0002664"}],"text":"ROUND: Pancreatic cancer is one of the most aggressive cancers, with tumor-induced myeloid-derived suppressor cells (MDSC) contributing to its pathogenesis and ineffective therapies. In response to cytokine/chemokine receptor activation, src homology 2 domain-containing inositol 5'-phosphatase-1 (SHIP-1) influences phosphatidylinositol-3-kinase (PI3K) signaling events, which regulate immunohomeostasis. We hypothesize that factors from murine pancreatic cancer cells cause the down-regulation of SHIP-1 expression, which may potentially contribute to MDSC expansion, and the suppression of CD8(+) T cell immune responses. Therefore, we sought to determine the role of SHIP-1 in solid tumor progression, such as murine pancreatic cancer.\nMETHODOLOGY AND PRINCIPAL FINDINGS: Immunocompetent C57BL/6 mice were inoculated with either murine Panc02 cells (tumor-bearing [TB] mice) or Phosphate Buffer Saline (PBS) (control mice). Cytometric Bead Array (CBA) analysis of supernatants of cultured Panc02 detected pro-inflammatory cytokines such as IL-6, IL-10 and MCP-1. TB mice showed a significant increase in serum levels of pro-inflammatory factors IL-6 and MCP-1 measured by CBA. qRT-PCR and Western blot analyses revealed the in vivo down-regulation of SHIP-1 expression in splenocytes from TB mice. Western blot analyses also detected reduced SHIP-1 activity, increased AKT-1 and BAD hyper-phosphorylation and up-regulation of BCL-2 expression in splenocytes from TB mice. In vitro, qRT-PCR and Western blot analyses detected reduced SHIP-1 mRNA and protein expression in control splenocytes co-cultured with Panc02 cells. Flow cytometry results showed significant expansion of MDSC in peripheral blood and splenocytes from TB mice. AutoMACS sorted TB MDSC exhibited hyper-phosphorylation of AKT-1 and over-expression of BCL-2 detected by western blot analysis. TB MDSC significantly suppressed antigen-specific CD8(+) T cell immune responses in vitro.\nCONCLUSION/SIGNIFICANCE: SHIP-1 may regulate immune development that impacts MDSC expansion and function, contributing to pancreatic tumor progression. Thus, SHIP-1 can be a potential therapeutic target to help restore immunohomeostasis and improve therapeutic responses in patients with pancreatic cancer"}

    Allie

    {"project":"Allie","denotations":[{"id":"SS1_22132131_2_0","span":{"begin":83,"end":115},"obj":"expanded"},{"id":"SS2_22132131_2_0","span":{"begin":117,"end":121},"obj":"abbr"},{"id":"SS1_22132131_3_0","span":{"begin":238,"end":296},"obj":"expanded"},{"id":"SS2_22132131_3_0","span":{"begin":298,"end":304},"obj":"abbr"},{"id":"SS1_22132131_3_1","span":{"begin":317,"end":346},"obj":"expanded"},{"id":"SS2_22132131_3_1","span":{"begin":348,"end":352},"obj":"abbr"},{"id":"SS1_22132131_7_0","span":{"begin":854,"end":867},"obj":"expanded"},{"id":"SS2_22132131_7_0","span":{"begin":869,"end":871},"obj":"abbr"},{"id":"SS1_22132131_7_1","span":{"begin":882,"end":905},"obj":"expanded"},{"id":"SS2_22132131_7_1","span":{"begin":907,"end":910},"obj":"abbr"},{"id":"SS1_22132131_8_0","span":{"begin":928,"end":949},"obj":"expanded"},{"id":"SS2_22132131_8_0","span":{"begin":951,"end":954},"obj":"abbr"}],"relations":[{"id":"AE1_22132131_2_0","pred":"abbreviatedTo","subj":"SS1_22132131_2_0","obj":"SS2_22132131_2_0"},{"id":"AE1_22132131_3_0","pred":"abbreviatedTo","subj":"SS1_22132131_3_0","obj":"SS2_22132131_3_0"},{"id":"AE1_22132131_3_1","pred":"abbreviatedTo","subj":"SS1_22132131_3_1","obj":"SS2_22132131_3_1"},{"id":"AE1_22132131_7_0","pred":"abbreviatedTo","subj":"SS1_22132131_7_0","obj":"SS2_22132131_7_0"},{"id":"AE1_22132131_7_1","pred":"abbreviatedTo","subj":"SS1_22132131_7_1","obj":"SS2_22132131_7_1"},{"id":"AE1_22132131_8_0","pred":"abbreviatedTo","subj":"SS1_22132131_8_0","obj":"SS2_22132131_8_0"}],"text":"ROUND: Pancreatic cancer is one of the most aggressive cancers, with tumor-induced myeloid-derived suppressor cells (MDSC) contributing to its pathogenesis and ineffective therapies. In response to cytokine/chemokine receptor activation, src homology 2 domain-containing inositol 5'-phosphatase-1 (SHIP-1) influences phosphatidylinositol-3-kinase (PI3K) signaling events, which regulate immunohomeostasis. We hypothesize that factors from murine pancreatic cancer cells cause the down-regulation of SHIP-1 expression, which may potentially contribute to MDSC expansion, and the suppression of CD8(+) T cell immune responses. Therefore, we sought to determine the role of SHIP-1 in solid tumor progression, such as murine pancreatic cancer.\nMETHODOLOGY AND PRINCIPAL FINDINGS: Immunocompetent C57BL/6 mice were inoculated with either murine Panc02 cells (tumor-bearing [TB] mice) or Phosphate Buffer Saline (PBS) (control mice). Cytometric Bead Array (CBA) analysis of supernatants of cultured Panc02 detected pro-inflammatory cytokines such as IL-6, IL-10 and MCP-1. TB mice showed a significant increase in serum levels of pro-inflammatory factors IL-6 and MCP-1 measured by CBA. qRT-PCR and Western blot analyses revealed the in vivo down-regulation of SHIP-1 expression in splenocytes from TB mice. Western blot analyses also detected reduced SHIP-1 activity, increased AKT-1 and BAD hyper-phosphorylation and up-regulation of BCL-2 expression in splenocytes from TB mice. In vitro, qRT-PCR and Western blot analyses detected reduced SHIP-1 mRNA and protein expression in control splenocytes co-cultured with Panc02 cells. Flow cytometry results showed significant expansion of MDSC in peripheral blood and splenocytes from TB mice. AutoMACS sorted TB MDSC exhibited hyper-phosphorylation of AKT-1 and over-expression of BCL-2 detected by western blot analysis. TB MDSC significantly suppressed antigen-specific CD8(+) T cell immune responses in vitro.\nCONCLUSION/SIGNIFICANCE: SHIP-1 may regulate immune development that impacts MDSC expansion and function, contributing to pancreatic tumor progression. Thus, SHIP-1 can be a potential therapeutic target to help restore immunohomeostasis and improve therapeutic responses in patients with pancreatic cancer"}

    2015-BEL-Sample-2

    {"project":"2015-BEL-Sample-2","denotations":[{"id":"BEL:20087308","span":{"begin":1181,"end":1300},"obj":"bp(GOBP:\"response to tumor cell\") decreases r(MGI:Inpp5d)"},{"id":"BEL:20087310","span":{"begin":1302,"end":1474},"obj":"bp(GOBP:\"response to tumor cell\") increases p(MGI:Bcl2)"},{"id":"BEL:20087312","span":{"begin":1302,"end":1474},"obj":"bp(GOBP:\"response to tumor cell\") decreases p(MGI:Inpp5d,pmod(P))"},{"id":"BEL:20087314","span":{"begin":1302,"end":1474},"obj":"bp(GOBP:\"response to tumor cell\") increases p(MGI:Akt1,pmod(P))"},{"id":"BEL:20087316","span":{"begin":1302,"end":1474},"obj":"bp(GOBP:\"response to tumor cell\") increases p(MGI:Bad,pmod(P))"},{"id":"BEL:20087318","span":{"begin":1476,"end":1711},"obj":"bp(GOBP:\"response to tumor cell\") decreases r(MGI:Inpp5d)"},{"id":"BEL:20087320","span":{"begin":1476,"end":1711},"obj":"bp(GOBP:\"response to tumor cell\") decreases p(MGI:Inpp5d)"},{"id":"BEL:20087326","span":{"begin":0,"end":2261},"obj":"bp(GOBP:\"response to tumor cell\") increases p(MGI:Il6)"},{"id":"BEL:20087328","span":{"begin":0,"end":2261},"obj":"bp(GOBP:\"response to tumor cell\") increases p(MGI:Il10)"},{"id":"BEL:20087330","span":{"begin":0,"end":2261},"obj":"bp(GOBP:\"response to tumor cell\") increases p(MGI:Ccl2)"},{"id":"BEL:20087332","span":{"begin":1067,"end":2106},"obj":"bp(GOBP:\"response to tumor cell\") decreases r(MGI:Inpp5d)"},{"id":"BEL:20087336","span":{"begin":1067,"end":1841},"obj":"bp(GOBP:\"response to tumor cell\") decreases act(p(MGI:Inpp5d))"},{"id":"BEL:20087340","span":{"begin":1067,"end":1991},"obj":"bp(GOBP:\"response to tumor cell\") increases act(p(MGI:Akt1))"},{"id":"BEL:20087344","span":{"begin":1067,"end":2106},"obj":"bp(GOBP:\"response to tumor cell\") increases r(MGI:Bcl2)"},{"id":"BEL:20087348","span":{"begin":406,"end":2139},"obj":"bp(GOBP:\"response to tumor cell\") increases r(MGI:Bcl2)"},{"id":"BEL:20087350","span":{"begin":740,"end":1484},"obj":"bp(GOBP:\"response to tumor cell\") decreases p(MGI:Inpp5d)"},{"id":"BEL:20087352","span":{"begin":1181,"end":2261},"obj":"bp(GOBP:\"response to tumor cell\") decreases r(MGI:Inpp5d)"}],"text":"ROUND: Pancreatic cancer is one of the most aggressive cancers, with tumor-induced myeloid-derived suppressor cells (MDSC) contributing to its pathogenesis and ineffective therapies. In response to cytokine/chemokine receptor activation, src homology 2 domain-containing inositol 5'-phosphatase-1 (SHIP-1) influences phosphatidylinositol-3-kinase (PI3K) signaling events, which regulate immunohomeostasis. We hypothesize that factors from murine pancreatic cancer cells cause the down-regulation of SHIP-1 expression, which may potentially contribute to MDSC expansion, and the suppression of CD8(+) T cell immune responses. Therefore, we sought to determine the role of SHIP-1 in solid tumor progression, such as murine pancreatic cancer.\nMETHODOLOGY AND PRINCIPAL FINDINGS: Immunocompetent C57BL/6 mice were inoculated with either murine Panc02 cells (tumor-bearing [TB] mice) or Phosphate Buffer Saline (PBS) (control mice). Cytometric Bead Array (CBA) analysis of supernatants of cultured Panc02 detected pro-inflammatory cytokines such as IL-6, IL-10 and MCP-1. TB mice showed a significant increase in serum levels of pro-inflammatory factors IL-6 and MCP-1 measured by CBA. qRT-PCR and Western blot analyses revealed the in vivo down-regulation of SHIP-1 expression in splenocytes from TB mice. Western blot analyses also detected reduced SHIP-1 activity, increased AKT-1 and BAD hyper-phosphorylation and up-regulation of BCL-2 expression in splenocytes from TB mice. In vitro, qRT-PCR and Western blot analyses detected reduced SHIP-1 mRNA and protein expression in control splenocytes co-cultured with Panc02 cells. Flow cytometry results showed significant expansion of MDSC in peripheral blood and splenocytes from TB mice. AutoMACS sorted TB MDSC exhibited hyper-phosphorylation of AKT-1 and over-expression of BCL-2 detected by western blot analysis. TB MDSC significantly suppressed antigen-specific CD8(+) T cell immune responses in vitro.\nCONCLUSION/SIGNIFICANCE: SHIP-1 may regulate immune development that impacts MDSC expansion and function, contributing to pancreatic tumor progression. Thus, SHIP-1 can be a potential therapeutic target to help restore immunohomeostasis and improve therapeutic responses in patients with pancreatic cancer"}