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  • Open Access

    ARTICLE

    Induction of Multidrug Resistance of Acute Myeloid Leukemia Cells by Cocultured Stromal Cells via Upregulation of the PI3K/Akt Signaling Pathway

    Ping Chen*, Qing Jin*, Qiang Fu*, Peidong You*, Xi Jiang*, Qin Yuan*, Huifang Huang

    Oncology Research, Vol.24, No.4, pp. 215-223, 2016, DOI:10.3727/096504016X14634208143021

    Abstract This study aimed to investigate the role of the PI3K/Akt signaling pathway in multidrug resistance of acute myeloid leukemia (AML) cells induced by cocultured stromal cells. Human AML cell lines HL-60 and U937 were adhesion cocultured with human bone marrow stromal cell line HS-5 cells. Such coculturing induced HL-60 and U937 cells resistant to chemotherapeutic drugs including daunorubicin (DNR), homoharringtonine (HHT), and cytosine arabinoside (Ara-C). The coculturing-induced resistance of AML cells to DNR, HHT, and Ara-C can be partially reversed by inhibition of the PI3K/Akt signaling pathway. Clinically, AML patients with a low level of More >

  • Open Access

    ARTICLE

    Knockdown of HPIP Inhibits the Proliferation and Invasion of Head-and-Neck Squamous Cell Carcinoma Cells by Regulating PI3K/Akt Signaling Pathway

    Yangjing Chen, Ruimin Zhao, Qian Zhao, Yuan Shao, Shaoqiang Zhang

    Oncology Research, Vol.24, No.3, pp. 153-160, 2016, DOI:10.3727/096504016X14612603423476

    Abstract Hematopoietic pre-B-cell leukemia transcription factor (PBX)-interacting protein (HPIP/PBXIP1) is a corepressor for the transcription factor PBX. Previous studies showed that HPIP is frequently overexpressed in many tumors. However, the role of HPIP in head-and-neck squamous cell carcinoma (HNSCC) has not yet been determined. Thus, we decided to investigate the effects and mechanisms of HPIP in HNSCC. Our results demonstrated that HPIP is highly expressed in human HNSCC cell lines and provides the first evidence that knockdown of HPIP obviously inhibits proliferation and migration/invasion in HNSCC cells in vitro, as well as inhibits tumor growth in More >

  • Open Access

    ARTICLE

    miR-34b Targets HSF1 to Suppress Cell Survival in Acute Myeloid Leukemia

    Gangcan Li, Yanping Song, Yunjie Zhang, Hao Wang, Jia Xie

    Oncology Research, Vol.24, No.2, pp. 109-116, 2016, DOI:10.3727/096504016X14611963142254

    Abstract Acute myeloid leukemia (AML) is the most lethal hematological malignancy, and the occurrence of chemoresistance prevents the achievement of complete remission following the standard therapy. MicroRNAs have been extensively investigated as critical regulators of hematopoiesis and leukemogenesis, and they represent a promising strategy for AML therapy. In this study, we identified miR-34b as a novel regulator in myeloid proliferation and apoptosis of leukemic cells. We found that miR-34b was developmentally upregulated in plasma and myeloid cells of healthy subjects, while it was significantly reduced in blood samples of patients with AML and AML cell lines.… More >

  • Open Access

    ARTICLE

    miR-187-5p Regulates Cell Growth and Apoptosis in Acute Lymphoblastic Leukemia via DKK2

    Ye Lou*1, Lei Liu†1, Lihui Zhan, Xuewei Wang§, Hua Fan

    Oncology Research, Vol.24, No.2, pp. 89-97, 2016, DOI:10.3727/096504016X14597766487753

    Abstract Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy and causes a high rate of mortality in affected adults. Many subtypes of ALL exist with disruptions in distinct genetic pathways, including those regulated by miRNAs. Here we identify miR-187-5p as being highly upregulated in B-cell ALL and a driver of cellular proliferation and suppressor of apoptosis. We show that miR-187-5p directly targets the 3'-UTR of DKK2 to mediate these effects. We further determine that inhibition of DKK2 by miR-187-5p in Nalm-6 B cells leads to inappropriate activation of Wnt/β-catenin signaling. Together, these findings reveal More >

  • Open Access

    ARTICLE

    Mitoxantrone and Etoposide for the Treatment of Acute Myeloid Leukemia Patients in First Relapse

    Annie Im, Ali Amjad, Mounzer Agha, Anastasios Raptis, Jing-Zhou Hou, Rafic Farah, Seah Lim, Alison Sehgal, Kathleen A. Dorritie, Robert L. Redner, Brian McLaughlin, Yongli Shuai, Shrina Duggal, Michael Boyiadzis

    Oncology Research, Vol.24, No.2, pp. 73-80, 2016, DOI:10.3727/096504016X14586627440156

    Abstract Relapsed acute myeloid leukemia (AML) represents a major therapeutic challenge. Achieving complete remission (CR) with salvage chemotherapy is the first goal of therapy for relapsed AML. However, there is no standard salvage chemotherapy. The current study evaluated outcomes and prognostic factors for achievement of CR in 91 AML patients in first relapse who were treated with the mitoxantrone–etoposide combination regimen. The overall response rate (CR and CRi) was 25%. Factors that were associated with a lower rate of CR included older age, shorter duration of first CR, low hemoglobin, and low platelet count. The median… More >

  • Open Access

    ARTICLE

    miR-1193 Suppresses the Proliferation and Invasion of Human T-Cell Leukemia Cells Through Directly Targeting the Transmembrane 9 Superfamily 3 (TM9SF3)

    Liyun Shen, Xingjun Du, Hongyan Ma, Shunxi Mei

    Oncology Research, Vol.25, No.9, pp. 1643-1651, 2017, DOI:10.3727/096504017X14908284471361

    Abstract miRNAs have been involved in various types of cancer, including T-cell leukemia. In this study, the role of miR-1193 in the proliferation and invasion of T-cell leukemia cells was explored. First, we found that miR-1193 was sharply downregulated in T-cell leukemia cells when compared with normal T cells. miR-1193 markedly decreased the proliferation and invasion in Jurkat human T-cell leukemia cells. Transmembrane 9 superfamily 3 (TM9SF3) was then predicted to be a potential target gene of miR-1193, the levels of which displayed a strongly negative correlation with miR-1193 levels in T-cell leukemia patients. We confirmed More >

  • Open Access

    ARTICLE

    Leukemia Inhibitory Factor Promotes Aggressiveness of Chordoma

    Sukru Gulluoglu*†, Mesut Sahin, Emre Can Tuysuz, Cumhur Kaan Yaltirik§, Aysegul Kuskucu*, Ferda Ozkan, Fikrettin Sahin, Ugur Ture§, Omer Faruk Bayrak*

    Oncology Research, Vol.25, No.7, pp. 1177-1188, 2017, DOI:10.3727/096504017X14874349473815

    Abstract Chordomas are rare tumors of the spine and skull base that are locally destructive and resistant to chemotherapy and radiation therapy, with a poor prognosis and limited therapeutic options. Chordoma patients have a long life expectancy with high mortality from the disease. Cancer stem cells, which are known to exist in chordomas, have extensive proliferative and self-renewal potential and are responsible for maintaining tumor heterogeneity along with chemotherapy and radiotherapy resistance. Leukemia inhibitory factor (LIF) has multiple functions in stem cell biology, the immune response, and cancer, and is potentially a key molecule that allows… More >

  • Open Access

    ARTICLE

    miR-92a Inhibits Proliferation and Induces Apoptosis by Regulating Methylenetetrahydrofolate Dehydrogenase 2 (MTHFD2) Expression in Acute Myeloid Leukemia

    Yueli Gu*, Jinchun Si, Xichun Xiao*, Ying Tian*, Shuo Yang*

    Oncology Research, Vol.25, No.7, pp. 1069-1079, 2017, DOI:10.3727/096504016X14829256525028

    Abstract Aberrant expression of microRNA-92a (miR-92a) has been investigated in various cancers. However, the function and mechanism of miR-92a in acute myeloid leukemia (AML) remain to be elucidated. Our data showed that miR-92a was evidently downregulated and methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) was remarkably upregulated in AML cell lines HL-60 and THP-1. Dual luciferase reporter assay revealed that MTHFD2 was a direct target of miR-92a. Gain- and loss-of-function analysis demonstrated that MTHFD2 knockdown or miR-92a overexpression notably inhibited proliferation and promoted apoptosis of AML cell lines. Restoration of MTHFD2 expression reversed proliferation inhibition and apoptosis induction of More >

  • Open Access

    ARTICLE

    A Wnt Pathway Activator Induces Apoptosis and Cell Death in Mouse Monocytic Leukemia Cells

    Yoshiro Kato*, Yoshikazu Naiki, Takayuki Komatsu, Kazuko Takahashi, Jiro Nakamura*, Naoki Koide

    Oncology Research, Vol.25, No.4, pp. 479-483, 2017, DOI:10.3727/096504016X14721731148893

    Abstract A Wnt agonist, 2-amino-4-[3,4-(methylenedioxy)benzylamino]-6-(3-methoxyphenyl) pyrimidine, is a cellpermeable pyrimidine compound that has been shown to mimic the effect of Wnt. In this study, leukemic mouse cell lines, RAW 264.7 and J774.1, were incubated with the Wnt agonist. The Wnt agonist showed cell death in the concentration of 1–10 mM. The Wnt agonist did not show inhibition of GSK-3β activity but induced β-catenin accumulation in the nucleus. The Wnt agonist showed caspase-independent cell death, but no further involvement in cell death ER stress signaling. Here we discuss the possible mechanism of Wnt agonist-induced apoptotic cell death More >

  • Open Access

    ARTICLE

    Long Noncoding RNA Urothelial Carcinoma-Associated 1 Promotes the Proliferation and Metastasis of Human Lung Tumor Cells by Regulating MicroRNA-144

    Dagang Li*, Huizong Li, Yuping Yang*, Le Kang*

    Oncology Research, Vol.26, No.4, pp. 537-546, 2018, DOI:10.3727/096504017X15009792179602

    Abstract Long noncoding RNA urothelial carcinoma-associated 1 (lncRNA UCA1) has gained more attention in recent years due to its oncogenic roles in various cancers. MicroRNA-144 (miR-144) participates in the regulation of the growth of many cancer cells. This study investigated the interaction between lncRNA UCA1 and miR-144 in lung cancer cells. The potential downstream protein of miR-144 was also assessed. Our results found that lncRNA UCA1 was highly expressed in human lung cancer A549, H517, H4006, H1299, and H1650 cells compared to normal embryonic lung WI-38 and HEL-1 cells. Knockdown of lncRNA UCA1 significantly inhibited lung More >

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