http://chineseinput.net/에서 pinyin(병음)방식으로 중국어를 변환할 수 있습니다.
변환된 중국어를 복사하여 사용하시면 됩니다.
Role of ADP receptors on platelets in the growth of ovarian cancer
Cho, Min Soon,Noh, Kyunghee,Haemmerle, Monika,Li, Dan,Park, Hyun,Hu, Qianghua,Hisamatsu, Takeshi,Mitamura, Takashi,Mak, Sze Ling Celia,Kunapuli, Satya,Ma, Qing,Sood, Anil K.,Afshar-Kharghan, Vahid American Society of Hematology 2017 Blood Vol.130 No.10
<P>We investigated the effect of platelets on ovarian cancer and the role of adenosine diphosphate (ADP) receptors (P2Y12 and P2Y1) on platelets in the growth of primary ovarian cancer tumors. We showed that in murine models of ovarian cancer, a P2Y12 inhibitor (ticagrelor) reduced tumor growth by 60% compared with aspirin and by 75% compared with placebo. In P2Y12(-/-) mice, the growth of syngeneic ovarian cancer tumors was reduced by >85% compared with wild-type (WT) mice. In contrast, there was no difference in tumor growth between P2Y1(-/-) and WT mice. Reconstitution of hematopoiesis in irradiated P2Y12(-/-) mice by hematopoietic progenitor cells from WT mice (WT -> P2Y12(-/-)) restored tumor growth in P2Y12(-/-) mice. Finally, knockdown of ecto-apyrase (CD39) on ovarian cancer cells increased tumor growth in tumor-bearing mice. Although in the absence of platelets, ADP, the P2Y12 inhibitor, recombinant apyrase, or knockdown of CD39 did not affect cancer cell proliferation, in the presence of platelets, the P2Y12 inhibitor and recombinant apyrase reduced and knockdown of CD39 increased platelet-enhanced cancer cell proliferation. These results suggest that P2Y12 on platelets and ADP concentration at the interface between cancer cells and platelets affect the growth of primary ovarian cancer tumors in mice. If additional studies in mice and in pilot human trials confirm our results, inhibition of P2Y12 might be a new therapeutic option that can be used in adjuvant to the traditional surgery and chemotherapy in patients with ovarian cancer.</P>
Systematic characterization of A-to-I RNA editing hotspots in microRNAs across human cancers
Wang, Yumeng,Xu, Xiaoyan,Yu, Shuangxing,Jeong, Kang Jin,Zhou, Zhicheng,Han, Leng,Tsang, Yiu Huen,Li, Jun,Chen, Hu,Mangala, Lingegowda S.,Yuan, Yuan,Eterovic, A. Karina,Lu, Yiling,Sood, Anil K.,Scott, Cold Spring Harbor Laboratory Press 2017 Genome research Vol.27 No.7
<P>RNA editing, a widespread post-transcriptional mechanism, has emerged as a new player in cancer biology. Recent studies have reported key roles for individual miRNA editing events, but a comprehensive picture of miRNA editing in human cancers remains largely unexplored. Here, we systematically characterized the miRNA editing profiles of 8595 samples across 20 cancer types from miRNA sequencing data of The Cancer Genome Atlas and identified 19 adenosine-to-inosine (A-to-I) RNA editing hotspots. We independently validated 15 of them by perturbation experiments in several cancer cell lines. These miRNA editing events show extensive correlations with key clinical variables (e.g., tumor subtype, disease stage, and patient survival time) and other molecular drivers. Focusing on the RNA editing hotspot in miR-200b, a key tumor metastasis suppressor, we found that the miR-200b editing level correlates with patient prognosis opposite to the pattern observed for the wild-type miR-200b expression. We further experimentally showed that, in contrast to wild-type miRNA, the edited miR-200b can promote cell invasion and migration through its impaired ability to inhibit <I>ZEB1/ZEB2</I> and acquired concomitant ability to repress new targets, including <I>LIFR</I>, a well-characterized metastasis suppressor. Our study highlights the importance of miRNA editing in gene regulation and suggests its potential as a biomarker for cancer prognosis and therapy.</P>
Han, Hee Dong,Byeon, Yeongseon,Kang, Tae Heung,Jung, In Duk,Lee, Jeong-Won,Shin, Byung Cheol,Lee, Young Joo,Sood, Anil K,Park, Yeong-Min DOVE MEDICAL PRESS 2016 INTERNATIONAL JOURNAL OF NANOMEDICINE Vol.11 No.-
<P>Dendritic cells (DCs) are potent professional antigen-presenting cells that are capable of initiating a primary immune response and activating T cells, and they play a pivotal role in the immune responses of the host to cancer. Prior to antigen presentation, efficient antigen and adjuvant uptake by DCs is necessary to induce their maturation and cytokine generation. Nanoparticles (NPs) are capable of intracellular delivery of both antigen and adjuvant to DCs. Here, we developed an advanced poly(<SMALL>D</SMALL>,<SMALL>L</SMALL>-lactide-co-glycolide) (PLGA)-NP encapsulating both ovalbumin (OVA) as a model antigen and polyinosinic-polycytidylic acid sodium salt (Toll-like receptor 3 ligand) as an adjuvant to increase intracellular delivery and promote DC maturation. The PLGA-NPs were taken up by DCs, and their uptake greatly facilitated major histocompatibility class I antigen presentation in vitro. Moreover, vaccination with PLGA-NP-treated DCs led to the generation of ovalbumin-specific CD8<SUP>+</SUP> T cells, and the resulting antitumor efficacy was significantly increased in EG.7 and TC-1 tumor-bearing mice compared to control mice (<I>P</I><0.01). Taken together, these findings demonstrated that the PLGA-NP platform may be an effective method for delivering tumor-specific antigens or adjuvants to DCs.</P>
FOXM1 mediates Dox resistance in breast cancer by enhancing DNA repair
Park, Yun-Yong,Jung, Sung Yun,Jennings, Nicholas B,Rodriguez-Aguayo, Cristian,Peng, Guang,Lee, Se-Ran,Kim, Sang Bae,Kim, Kyounghyun,Leem, Sun-Hee,Lin, Shiaw-Yih,Lopez-Berestein, Gabriel,Sood, Anil K,L Oxford University Press 2012 Carcinogenesis Vol.33 No.10
<B>Abstract</B><P>Transcription factors are direct effectors of altered signaling pathways in cancer and frequently determine clinical outcomes in cancer patients. To uncover new transcription factors that would determine clinical outcomes in breast cancer, we systematically analyzed gene expression data from breast cancer patients. Our results revealed that Forkhead box protein M1 (FOXM1) is the top-ranked survival-associated transcription factor in patients with triple-negative breast cancer. Surprisingly, silencing FOXM1 expression led breast cancer cells to become more sensitive to doxorubicin (Dox). We found that FOXM1-dependent resistance to Dox is mediated by regulating DNA repair genes. We further demonstrated that NFκB1 interacts with FOXM1 in the presence of Dox to protect breast cancer cells from DNA damage. Finally, silencing FOXM1 expression in breast cancer cells in a mouse xenograft model significantly sensitized the cells to Dox. Our systematic approaches identified an unexpected role of FOXM1 in Dox resistance by regulating DNA repair genes, and our findings provide mechanistic insights into how FOXM1 mediates resistance to Dox and evidence that FOXM1 may be a promising therapeutic target for sensitizing breast cancer cells to Dox.</P>
Kim, Ga Hee,Won, Ji Eun,Byeon, Yeongseon,Kim, Min Gi,Wi, Tae In,Lee, Jae Myeong,Park, Yun-Yong,Lee, Jeong-Won,Kang, Tae Heung,Jung, In Duk,Shin, Byung Cheol,Ahn, Hyung Jun,Lee, Young Joo,Sood, Anil K. TaylorFrancis 2018 DRUG DELIVERY Vol.25 No.1
<P><B>Abstract</B></P><P>Angiogenesis plays an essential role in the growth and metastasis of tumor cells, and the modulation of angiogenesis can be an effective approach for cancer therapy. We focused on silencing the angiogenic gene PLXDC1 as an important factor for anti-angiogenesis tumor therapy. Herein, we developed PLXDC1 small interfering siRNA (siRNA)-incorporated chitosan nanoparticle (CH-NP/siRNA) coated with hyaluronic acid (HA) to target the CD44 receptor on tumor endothelial cells. This study aimed to improve targeted delivery and enhance therapeutic efficacy for tumor anti-angiogenesis. The HA-CH-NP/siRNA was 200 ± 10 nm in size with a zeta potential of 26.4 mV. The loading efficiency of siRNA to the HA-CH-NP/siRNA was up to 60%. The selective binding of HA-CH-NP/siRNA to CD44-positive tumor endothelial cells increased by 2.1-fold compared with that of the CD44 nontargeted CH-NP/siRNA. PLXDC1 silencing by the HA-CH-NP/siRNA significantly inhibited tumor growth in A2780 tumor-bearing mice compared with that in the control group (<I>p</I> < .01), and mRNA expression of PLXDC1 was significantly reduced in the HA-CH-NP/siRNA-treated group. Furthermore, treatment with HA-CH-NP/siRNA resulted in significant inhibition of cell proliferation (<I>p</I> < .001), reduced microvessel density (<I>p</I> < .001), and increased cell apoptosis (<I>p</I> < .001). This study demonstrates that HA-CH-NP/siRNA is a highly selective delivery platform for siRNA, and has broad potential to be used in anti-angiogenesis tumor therapy.</P>