CD40 ligation provides signals central to chronic lymphocytic leukemia (CLL) cell survival and proliferation. The release of soluble CD40 (sCD40) may impact on both these signals and CD40 targeted therapies. In this s...CD40 ligation provides signals central to chronic lymphocytic leukemia (CLL) cell survival and proliferation. The release of soluble CD40 (sCD40) may impact on both these signals and CD40 targeted therapies. In this study we investigated the prognostic significance of plasma sCD40 inuntreated CLL patients (n = 34). We report that 56% had levels higher than those of normal donors and that elevated levels were associated with significantly shorter treatment free (TFS) and overall survival. In bivariate analysis sCD40 remained a significant marker of TFS independent of Binet staging, CD38 positivity and lymphocyte count. RT-PCR analysis demonstrated that CLL cells expressed transcripts encoding putative sCD40. These results suggest sCD40 may play a role in CLL progression and that its function, prognostic significance and potential impact on antibody based therapies should be further investigated.展开更多
Reliance on glycolysis for energy production is considered a hallmark of cancer and the glycolytic enzyme a-enolase is overexpressed in a range of cancer types.However,recent studies have revealed that a-enolase is in...Reliance on glycolysis for energy production is considered a hallmark of cancer and the glycolytic enzyme a-enolase is overexpressed in a range of cancer types.However,recent studies have revealed that a-enolase is involved in a variety of unrelated physiological processes and can be found in multiple unexpected cellular locations.This review focuses on the unlikely role of a-enolase as an extracellular plasminogen-binding receptor localised to the plasma membrane.Conversion of plasminogen to plasmin on the surface of cancer cells enhances their ability to invade through stroma by activating collagenases and degrading fibrin as well as extracellular matrix proteins.Increased expression of a-enolase is associated with increased migration and invasion of cancer cells,and decreased metastasis-free survival in patients with several cancer types,including non-small cell lung,pancreatic,breast and colorectal cancers.Due to its overexpression in a range of cancer types and multi-functional roles in key areas of tumour metabolism and metastasis,a-enolase may be useful as a universal cancer prognostic biomarker or therapeutic target.展开更多
文摘CD40 ligation provides signals central to chronic lymphocytic leukemia (CLL) cell survival and proliferation. The release of soluble CD40 (sCD40) may impact on both these signals and CD40 targeted therapies. In this study we investigated the prognostic significance of plasma sCD40 inuntreated CLL patients (n = 34). We report that 56% had levels higher than those of normal donors and that elevated levels were associated with significantly shorter treatment free (TFS) and overall survival. In bivariate analysis sCD40 remained a significant marker of TFS independent of Binet staging, CD38 positivity and lymphocyte count. RT-PCR analysis demonstrated that CLL cells expressed transcripts encoding putative sCD40. These results suggest sCD40 may play a role in CLL progression and that its function, prognostic significance and potential impact on antibody based therapies should be further investigated.
基金the Calvary Mater Newcastle and Hunter Medical Research Institute.
文摘Reliance on glycolysis for energy production is considered a hallmark of cancer and the glycolytic enzyme a-enolase is overexpressed in a range of cancer types.However,recent studies have revealed that a-enolase is involved in a variety of unrelated physiological processes and can be found in multiple unexpected cellular locations.This review focuses on the unlikely role of a-enolase as an extracellular plasminogen-binding receptor localised to the plasma membrane.Conversion of plasminogen to plasmin on the surface of cancer cells enhances their ability to invade through stroma by activating collagenases and degrading fibrin as well as extracellular matrix proteins.Increased expression of a-enolase is associated with increased migration and invasion of cancer cells,and decreased metastasis-free survival in patients with several cancer types,including non-small cell lung,pancreatic,breast and colorectal cancers.Due to its overexpression in a range of cancer types and multi-functional roles in key areas of tumour metabolism and metastasis,a-enolase may be useful as a universal cancer prognostic biomarker or therapeutic target.
