Browsing by Author "Yang, Ling"

Now showing 1 - 3 of 3
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    Activation of hedgehog signaling is not a frequent event in ovarian cancers
    (BioMed Central, 2009-11-27) Yang, Ling; He, Jing; Huang, Shuhong; Zhang, Xiaoli; Bian, Yuehong; He, Nonggao; Zhang, Hongwei; Xie, Jingwu; Pediatrics, School of Medicine
    The hedgehog (Hh) signaling pathway regulates many processes of development and tissue homeostasis. Activation of hedgehog signaling has been reported in about 30% of human cancer including ovarian cancer. Inhibition of hedgehog signaling has been pursued as an effective strategy for cancer treatment including an ongoing phase II clinical trial in ovarian cancer. However, the rate of hedgehog signaling activation in ovarian cancer was reported differently by different groups. To predict the successful for future clinical trials of hedgehog signaling inhibitors in ovarian cancer, we assessed hedgehog pathway activation in 34 ovarian epithelial tumor specimens through analyses of target gene expression by in-situ hybridization, immunohistochemistry, RT-PCR and real-time PCR. In contrast to previous reports, we only detected a small proportion of ovarian cancers with hedgehog target gene expression, suggesting that identification of the tumors with activated hedgehog signaling activation will facilitate chemotherapy with hedgehog signaling inhibitors.
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    Defective TGFβ signaling in bone marrow-derived cells prevents Hedgehog-induced skin tumors
    (American Association for Cancer Research, 2014-01-15) Fan, Qipeng; Gu, Dongsheng; Liu, Hailan; Yang, Ling; Zhang, Xiaoli; Yoder, Mervin C.; Kaplan, Mark H.; Xie, Jingwu; Department of Pediatrics, IU School of Medicine
    Hedgehog (Hh) signaling in cancer cells drives changes in the tumor microenvironment that are incompletely understood. Here we report that Hh- driven tumors exhibit an increase in myeloid-derived suppressor cells (MDSC) and a decrease in T cells, indicative of an immune suppressive tumor microenvironment. This change was associated with activated TGFβ signaling in several cell types in BCCs. We determined that TGFβ signaling in bone marrow (BM)-derived cells, not keratinocytes, regulates MDSC and promotes tumor development. Tgfbr2 deficiency in the BM-derived cells also reduced the size of previously developed tumors in mice. We identified CCL2 as the major chemokine attracting MDSC to tumor, whose expression was Tgfbr2-dependent, whereas its receptor CCR2 was highly expressed in MDSC population. CCL2 alone was sufficient to induce migration of MDSC. Moreover, the CCR2 inhibitors prevented MDSC migration towards skin cells in vitro, reduced MDSC accumulation and Hh signaling-driven tumor development in mice. Our results reveal a signaling network critical for Hh signaling in cancer cells to establish an effective immune suppressive microenvironment during tumor development.
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    The Role of the Hedgehog Pathway in Chemoresistance of Gastrointestinal Cancers
    (MDPI, 2021) Liang, Yabing; Yang, Ling; Xie, Jingwu; Pediatrics, School of Medicine
    The hedgehog pathway, which plays a significant role in embryonic development and stem cell regulation, is activated in gastrointestinal cancers. Chemotherapy is widely used in cancer treatment. However, chemoresistance becomes a substantial obstacle in cancer therapy. This review focuses on the recent advances in the hedgehog pathway’s roles in drug resistance of gastrointestinal cancers and the novel drugs and strategies targeting hedgehog signaling.