Guanylate-binding proteins(GBPs) are interferonstimulated factors involved in the defense against cellular pathogens and inflammation. These proteins, particularly GBP-1, the most prominent member of the family, have ...Guanylate-binding proteins(GBPs) are interferonstimulated factors involved in the defense against cellular pathogens and inflammation. These proteins, particularly GBP-1, the most prominent member of the family, have been established as reliable markers of interferon-γ-activated cells in various diseases, including colorectal carcinoma(CRC) and inflammatory bowel diseases(IBDs). In CRC, GBP-1 expression is associated with a Th1-dominated angiostatic micromilieu and is correlated with a better outcome. Inhibition of tumor growth by GBP-1 is the result of its strong antiangiogenic activity as well as its direct anti-tumorigenic effect on tumor cells. In IBD, GBP-1 mediates the anti-proliferative effects of interferon-γ on intestinal epithelial cells. In addition, it plays a protective role on the mucosa by preventing cell apoptosis, by inhibiting angiogenesis and by regulating the T-cell receptor signaling. These functions rely to a large extent on the ability of GBP-1 to interact with and remodel the actin cytoskeleton.展开更多
Ovarian cancer is the gynecological cancer with the poorest prognosis. One significant reason is the development of resistance to the chemotherapeutic drugs used in its treatment. The large GTPase, hGBP-1, has been im...Ovarian cancer is the gynecological cancer with the poorest prognosis. One significant reason is the development of resistance to the chemotherapeutic drugs used in its treatment. The large GTPase, hGBP-1, has been implicated in paclitaxel resistance in ovarian cell lines. Forced expression of hGBP-1 in SKOV3 ovarian cancer cells protects them from paclitaxel-induced cell death. However, prior to this study, nothing was known about whether hGBP-1 was expressed in ovarian tumors and whether its expression correlated with paclitaxel resistance. hGBP-1 is expressed in 17% of ovarian tumors from patients that have not yet received treatment. However, at least 80% of the ovarian tumors that recurred after therapies that included a taxane, either paclitaxel or docetaxel, were positive for hGBP-1. In addition, hGBP-1 expression predicts a significantly shorter progression-free survival in ovarian cancers. Based on these studies, hGBP-1 could prove to be a potential biomarker for paclitaxel resistance in ovarian cancer.展开更多
基金Supported by German Research Foundation,No.DFG-KFO257(sub-project 4)No.SFB796(sub-project B9)+1 种基金No.DFG-BR5196,and No.FOR2438(sub-project 2)Interdisciplinary Center for Clinical Research(IZKF)of the Clinical Center Erlangen
文摘Guanylate-binding proteins(GBPs) are interferonstimulated factors involved in the defense against cellular pathogens and inflammation. These proteins, particularly GBP-1, the most prominent member of the family, have been established as reliable markers of interferon-γ-activated cells in various diseases, including colorectal carcinoma(CRC) and inflammatory bowel diseases(IBDs). In CRC, GBP-1 expression is associated with a Th1-dominated angiostatic micromilieu and is correlated with a better outcome. Inhibition of tumor growth by GBP-1 is the result of its strong antiangiogenic activity as well as its direct anti-tumorigenic effect on tumor cells. In IBD, GBP-1 mediates the anti-proliferative effects of interferon-γ on intestinal epithelial cells. In addition, it plays a protective role on the mucosa by preventing cell apoptosis, by inhibiting angiogenesis and by regulating the T-cell receptor signaling. These functions rely to a large extent on the ability of GBP-1 to interact with and remodel the actin cytoskeleton.
文摘Ovarian cancer is the gynecological cancer with the poorest prognosis. One significant reason is the development of resistance to the chemotherapeutic drugs used in its treatment. The large GTPase, hGBP-1, has been implicated in paclitaxel resistance in ovarian cell lines. Forced expression of hGBP-1 in SKOV3 ovarian cancer cells protects them from paclitaxel-induced cell death. However, prior to this study, nothing was known about whether hGBP-1 was expressed in ovarian tumors and whether its expression correlated with paclitaxel resistance. hGBP-1 is expressed in 17% of ovarian tumors from patients that have not yet received treatment. However, at least 80% of the ovarian tumors that recurred after therapies that included a taxane, either paclitaxel or docetaxel, were positive for hGBP-1. In addition, hGBP-1 expression predicts a significantly shorter progression-free survival in ovarian cancers. Based on these studies, hGBP-1 could prove to be a potential biomarker for paclitaxel resistance in ovarian cancer.
