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Dihydroorotate dehydrogenase (DHODH) is a flavin-dependent enzyme crucial for de novo pyrimidine biosynthesis and is a promising drug target for the treatment of cancer and autoimmune diseases. Kawatani et al. identified a novel small-molecule DHODH inhibitor by proteomic profiling. Cell-based screening identified NPD723, which is reduced to H-006 in cells, as a potent inducer of myeloid differentiation. ChemProteoBase is a two-dimensional difference gel electrophoresis (2D-DIGE)-based proteomics database that includes profiles of proteomic perturbations induced by various inhibitors. Proteomic profiling with ChemProteoBase revealed that H-006 is a potent and selective DHODH inhibitor. The cover image depicts the structure of NPD723.

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  • Open AccessOpen Access

    ARTICLE

    Identification of a dihydroorotate dehydrogenase inhibitor that inhibits cancer cell growth by proteomic profiling

    MAKOTO KAWATANI1,2,*, HARUMI AONO2, SAYOKO HIRANUMA3, TAKESHI SHIMIZU3, MAKOTO MUROI1,2, TOSHIHIKO NOGAWA4, TOMOKAZU OHISHI5, SHUN-ICHI OHBA5, MANABU KAWADA5, KANAMI YAMAZAKI6, SHINGO DAN6, NAOSHI DOHMAE1, HIROYUKI OSADA2,7,*
    Oncology Research, Vol.31, No.6, pp. 833-844, 2023, DOI:10.32604/or.2023.030241
    (This article belongs to the Special Issue: Approach from Chemical Biology for Cancer Research)
    Abstract Dihydroorotate dehydrogenase (DHODH) is a central enzyme of the de novo pyrimidine biosynthesis pathway and is a promising drug target for the treatment of cancer and autoimmune diseases. This study presents the identification of a potent DHODH inhibitor by proteomic profiling. Cell-based screening revealed that NPD723, which is reduced to H-006 in cells, strongly induces myeloid differentiation and inhibits cell growth in HL-60 cells. H-006 also suppressed the growth of various cancer cells. Proteomic profiling of NPD723-treated cells in ChemProteoBase showed that NPD723 was clustered with DHODH inhibitors. H-006 potently inhibited human DHODH activity in vitro, whereas More >

  • Open AccessOpen Access

    ARTICLE

    Deoxynortryptoquivaline: A unique antiprostate cancer agent

    YOHKO YAMAZAKI1,*, MANABU KAWADA2, ISAO MOMOSE1
    Oncology Research, Vol.31, No.6, pp. 845-853, 2023, DOI:10.32604/or.2023.030266
    (This article belongs to the Special Issue: Approach from Chemical Biology for Cancer Research)
    Abstract The androgen receptor (AR) is a critical target in all the clinical stages of prostate cancer. To identify a new AR inhibitor, we constructed a new screening system using the androgen-dependent growth of prostate cancer cell lines as a screening indicator. We screened 50,000 culture broths of microorganisms using this screening system and found that the fermentation broth produced by a fungus inhibited androgen-dependent growth of human prostate cancer LNCaP cells without cytotoxicity. Purification of this culture medium was performed, and this resulted in deoxynortryptoquivaline (DNT) being identified as a novel inhibitor of AR function. More >

    Graphic Abstract

    Deoxynortryptoquivaline: A unique antiprostate cancer agent

  • Open AccessOpen Access

    ARTICLE

    Comprehensive molecular analysis to predict the efficacy of chemotherapy containing bevacizumab in patients with metastatic colorectal cancer

    SUNG HEE LIM1,#, HEE JIN CHO1,2,3,#, KYOUNG-MEE KIM4, HO YEONG LIM1, WON KI KANG1, JEEYUN LEE1, YOUNG SUK PARK1, HEE CHEOL KIM5,*, SEUNG TAE KIM1,*
    Oncology Research, Vol.31, No.6, pp. 855-866, 2023, DOI:10.32604/or.2023.030374
    Abstract Background: Although bevacizumab is an important treatment for metastatic colorectal cancer (CRC), not all patients with CRC benefit from it; in unselected patient populations, only modest survival benefits have been reported. Methods: We evaluated clinical outcomes in 110 patients using comprehensive molecular characterization to identify biomarkers for a response to bevacizumab-containing treatment. The molecular analysis comprised whole-exome sequencing, ribonucleic acid sequencing, and a methylation array on patient tissues. Results: Genomic and molecular characterization was successfully conducted in 103 patients. Six of 103 CRC samples were hypermutated, and none of the non-hypermutant tumors were microsatellite unstable. Among… More >

  • Open AccessOpen Access

    ARTICLE

    A novel isoxazole compound CM2-II-173 inhibits the invasive phenotype of triple-negative breast cancer cells

    EUN SOOK KIM1, SANGHEE KIM2, AREE MOON1,*
    Oncology Research, Vol.31, No.6, pp. 867-875, 2023, DOI:10.32604/or.2023.030411
    Abstract Invasion and metastasis are important hallmarks of breast cancer and are the leading cause of patient mortality. Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer characterized by a poor prognosis and a lack of effective targeted therapies. The present study investigated the inhibitory effect of a novel FTY720 derivative on the invasive phenotype of TNBC cells. Here, we showed that a novel compound with an isoxazole ring, 4-(3-Decylisoxazol-5-yl)-1-hydroxy-2-(hydroxymethyl)butan-2-aminium chloride (CM2-II-173), significantly inhibited invasiveness of MDA-MB-231 TNBC cells. Expression of matrix metalloproteinase (MMP)-9 and invasiveness of MCF10A normal breast cells induced by sphingosine-1-phosphate… More >

  • Open AccessOpen Access

    REVIEW

    Progress in research on tumor microenvironment-based spatial omics technologies

    FANGMEI XIE1,#, NAITE XI1,#, ZEPING HAN1,#, WENFENG LUO1, JIAN SHEN1, JINGGENG LUO2, XINGKUI TANG2, TING PANG1, YUBING LV1, JIABING LIANG1, LIYIN LIAO1, HAOYU ZHANG1, YONG JIANG1, YUGUANG LI3,*, JINHUA HE1,*
    Oncology Research, Vol.31, No.6, pp. 877-885, 2023, DOI:10.32604/or.2023.029494
    Abstract Spatial omics technology integrates the concept of space into omics research and retains the spatial information of tissues or organs while obtaining molecular information. It is characterized by the ability to visualize changes in molecular information and yields intuitive and vivid visual results. Spatial omics technologies include spatial transcriptomics, spatial proteomics, spatial metabolomics, and other technologies, the most widely used of which are spatial transcriptomics and spatial proteomics. The tumor microenvironment refers to the surrounding microenvironment in which tumor cells exist, including the surrounding blood vessels, immune cells, fibroblasts, bone marrow-derived inflammatory cells, various signaling More >

  • Open AccessOpen Access

    ARTICLE

    The DMRTA1-SOX2 positive feedback loop promotes progression and chemotherapy resistance of esophageal squamous cell carcinoma

    RUI ZHANG1,2,#, PENG ZHOU1,3,#, XIA OU4, PEIZHU ZHAO2, XIJING GUO2, MIAN XI5,*, CHEN QING1,*
    Oncology Research, Vol.31, No.6, pp. 887-897, 2023, DOI:10.32604/or.2023.030184
    (This article belongs to the Special Issue: Application of Multi-omics Analysis in Cancer Immunotherapy)
    Abstract Esophageal squamous cell carcinoma (ESCC) is among the most prevalent causes of cancer-related death in patients worldwide. Resistance to immunotherapy and chemotherapy results in worse survival outcomes in ESCC. It is urgent to explore the underlying molecular mechanism of immune evasion and chemoresistance in ESCC. Here, we conducted RNA-sequencing analysis in ten ESCC tissues from cisplatin-based neoadjuvant chemotherapy patients. We found that DMRTA1 was extremely upregulated in the non-pathologic complete response (non-pCR) group. The proliferation rate of esophageal squamous carcinoma cells was markedly decreased after knockdown of DMRTA1 expression, which could increase cisplatin sensitivity in More >

  • Open AccessOpen Access

    ARTICLE

    Deciphering key genes involved in cisplatin resistance in kidney renal clear cell carcinoma through a combined in silico and in vitro approach

    MUNEEBA MALIK1, MAMOONA MAQBOOL2, TOOBA NISAR3, TAZEEM AKHTER4, JAVED AHMED UJAN5,6, ALANOOD S. ALGARNI7, FAKHRIA A. AL JOUFI8, SULTAN SHAFI K. ALANAZI9, MOHAMMAD HADI ALMOTARED10, MOUNIR M. SALEM BEKHIT11, MUHAMMAD JAMIL12,*
    Oncology Research, Vol.31, No.6, pp. 899-916, 2023, DOI:10.32604/or.2023.030760
    (This article belongs to the Special Issue: Cancer Metastasis)
    Abstract The low survival rate of Kidney renal clear cell carcinoma (KIRC) patients is largely attributed to cisplatin resistance. Rather than focusing solely on individual proteins, exploring protein-protein interactions could offer greater insight into drug resistance. To this end, a series of in silico and in vitro experiments were conducted to identify hub genes in the intricate network of cisplatin resistance-related genes in KIRC chemotherapy. The genes involved in cisplatin resistance across KIRC were retrieved from the National Center for Biotechnology Information (NCBI) database using search terms as “Kidney renal clear cell carcinoma” and “Cisplatin resistance”. The genes… More >

  • Open AccessOpen Access

    ARTICLE

    CHRM3 is a novel prognostic factor of poor prognosis and promotes glioblastoma progression via activation of oncogenic invasive growth factors

    BIN ZHANG1,#, JIANYI ZHAO3,#, YONGZHI WANG2,#, HUA XU1, BO GAO1, GUANGNING ZHANG1, BIN HAN1, GUOHONG SONG1, JUNCHEN ZHANG1,*, WEI MENG1,*
    Oncology Research, Vol.31, No.6, pp. 917-927, 2023, DOI:10.32604/or.2023.030425
    (This article belongs to the Special Issue: Signaling Pathway Crosstalk in Malignant Tumors: Molecular Targets and Combinatorial Therapeutics)
    Abstract Glioblastoma (GBM) is the most aggressive cancer of the brain and has a high mortality rate due to the lack of effective treatment strategy. Clarification of molecular mechanisms of GBM’s characteristic invasive growth are urgently needed to improve the poor prognosis. Single-nuclear sequencing of primary and recurrent GBM samples revealed that levels of M3 muscarinic acetylcholine receptor (CHRM3) were significantly higher in the recurrent samples than in the primary samples. Moreover, immunohistochemical staining of an array of GBM samples showed that high levels of CHRM3 correlated with poor prognosis, consistent with The Cancer Genome Atlas More >

  • Open AccessOpen Access

    ARTICLE

    CircUCP2 promotes the tumor progression of non-small cell lung cancer through the miR-149/UCP2 pathway

    WEI DU1, FANG YIN1, YATING ZHONG1, MINJIE LUO1, ZHEN WANG2, PENG LIN2, QING LIU2,*, HAN YANG2,*
    Oncology Research, Vol.31, No.6, pp. 929-936, 2023, DOI:10.32604/or.2023.030611
    Abstract Non-small cell lung cancer (NSCLC) is a highly lethal cancer, and better treatments are urgently needed. Many studies have implicated circular RNAs (circRNAs) in the progression of multiple malignant tumors. Nonetheless, the functions of circRNAs in NSCLC remain unclear. To study new targets for the treatment of NSCLC, circRNA expression profiling was performed on NSCLC tissues and para-carcinoma nonmalignant tissues. RNA was isolated and used for circRNA sequencing. Biological studies were performed in vitro and in vivo to determine the functions of circRNAs in NSCLC, including their functions in cell proliferation and migration. How circRNAs function in More >

    Graphic Abstract

    CircUCP2 promotes the tumor progression of non-small cell lung cancer through the miR-149/UCP2 pathway

  • Open AccessOpen Access

    ARTICLE

    Polo-like kinase 1 suppresses lung adenocarcinoma immunity through necroptosis

    PENGCHENG ZHANG1,#,*, XINGLONG ZHANG2,#, YONGFU ZHU3, YIYI CUI1, JING XU4, WEIPING ZHANG1,*
    Oncology Research, Vol.31, No.6, pp. 937-953, 2023, DOI:10.32604/or.2023.030933
    (This article belongs to the Special Issue: Multi-Omics Approaches for Precision Medicine)
    Abstract Polo-like kinase 1 (PLK1) plays a crucial role in cell mitosis and has been associated with necroptosis. However, the role of PLK1 and necroptosis in lung adenocarcinoma (LA) remains unclear. In this study, we analyzed The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression databases to evaluate the prognostic value and mechanistic role of PLK1 in LA. PLK1 was found to be highly expressed in LA and was positively associated with advanced disease staging and poor survival outcomes. Functional enrichment analysis showed that PLK1 was involved in cell mitosis, neurotransmitter transmission, and drug metabolism. Further analysis… More >

    Graphic Abstract

    Polo-like kinase 1 suppresses lung adenocarcinoma immunity through necroptosis

  • Open AccessOpen Access

    ARTICLE

    ScRNA-seq reveals the correlation between M2 phenotype of tumor-associated macrophages and lymph node metastasis of breast cancer

    JUN SHEN1,#, HONGFANG MA2,#, YONGXIA CHEN3, JIANGUO SHEN1,*
    Oncology Research, Vol.31, No.6, pp. 955-966, 2023, DOI:10.32604/or.2023.029638
    (This article belongs to the Special Issue: Role of Reactive Oxygen Species and DNA Damage in Tumor Immunological Responses)
    Abstract The process of lymphatic metastasis was proved to be associated with podoplanin-expressing macrophages in breast cancer (BC). This study aimed to investigate the role of the M2 phenotype of tumor-associated macrophages and mine the key M2 macrophages-related genes for lymph node metastasis in BC. We downloaded the GSE158399 dataset from the Gene Expression Omnibus (GEO) database, which includes transcriptomic profiles of individual cells from primary tumors, negative lymph nodes (NLNs), and positive lymph nodes (PLNs) of breast cancer patients. The cell subsets were identified by clustering analysis after quality control of the scRNA-seq using Seurat.… More >

  • Open AccessOpen Access

    ARTICLE

    Identification of lncRNAs associated with T cells as potential biomarkers and therapeutic targets in lung adenocarcinoma

    LU SUN1,2, HUAICHENG TAN1, TING YU3, RUICHAO LIANG4,*
    Oncology Research, Vol.31, No.6, pp. 967-988, 2023, DOI:10.32604/or.2023.042309
    (This article belongs to the Special Issue: Multi-Omics Approaches for Precision Medicine)
    Abstract Lung adenocarcinoma (LUAD) is the most common and deadliest subtype of lung cancer. To select more targeted and effective treatments for individuals, further advances in classifying LUAD are urgently needed. The number, type, and function of T cells in the tumor microenvironment (TME) determine the progression and treatment response of LUAD. Long noncoding RNAs (lncRNAs), may regulate T cell differentiation, development, and activation. Thus, our aim was to identify T cell-related lncRNAs (T cell-Lncs) in LUAD and to investigate whether T cell-Lncs could serve as potential stratifiers and therapeutic targets. Seven T cell-Lncs were identified… More >

  • Open AccessOpen Access

    ARTICLE

    Long non-coding RNA H19 promotes proliferation in hepatocellular carcinoma cells via H19/miR-107/CDK6 axis

    ARCHITTAPON NOKKEAW1,2,3,#, PANNATHON THAMJAMRASSRI1,2,3,#, NAPHAT CHANTARAVISOOT1,4, PISIT TANGKIJVANICH1,2,*, CHAIYABOOT ARIYACHET1,2,*
    Oncology Research, Vol.31, No.6, pp. 989-1005, 2023, DOI:10.32604/or.2023.030395
    Abstract Hepatocellular carcinoma (HCC) is the leading cause of cancer death worldwide; nevertheless, current therapeutic options are limited or ineffective for many patients. Therefore, elucidation of molecular mechanisms in HCC biology could yield important insights for the intervention of novel therapies. Recently, various studies have reported dysregulation of long non-coding RNAs (lncRNAs) in the initiation and progression of HCC, including H19; however, the biological function of H19 in HCC remains unclear. Here, we show that knockdown of H19 disrupted HCC cell growth, impaired the G1-to-S phase transition, and promoted apoptosis, while overexpression of H19 yielded the… More >

    Graphic Abstract

    Long non-coding RNA H19 promotes proliferation in hepatocellular carcinoma cells via H19/miR-107/CDK6 axis

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