MAKOTO KAWATANI^1,2,*, HARUMI AONO², SAYOKO HIRANUMA³, TAKESHI SHIMIZU³, MAKOTO MUROI^1,2, TOSHIHIKO NOGAWA⁴, TOMOKAZU OHISHI⁵, SHUN-ICHI OHBA⁵, MANABU KAWADA⁵, KANAMI YAMAZAKI⁶, SHINGO DAN⁶, NAOSHI DOHMAE¹, HIROYUKI OSADA^2,7,*

Oncology Research, Vol.31, No.6, pp. 833-844, 2023, DOI:10.32604/or.2023.030241

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 NPD723 was approximately… More >

RUI ZHANG^1,2,#, PENG ZHOU^1,3,#, XIA OU⁴, PEIZHU ZHAO², XIJING GUO², MIAN XI^5,*, CHEN QING^1,*

Oncology Research, Vol.31, No.6, pp. 887-897, 2023, DOI:10.32604/or.2023.030184

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 ESCC. Additionally, suppression of DMRTA1… More >

JUN SHEN^1,#, HONGFANG MA^2,#, YONGXIA CHEN³, JIANGUO SHEN^1,*

Oncology Research, Vol.31, No.6, pp. 955-966, 2023, DOI:10.32604/or.2023.029638

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. The activation and migration capability… More >

FANGMEI XIE^1,#, NAITE XI^1,#, ZEPING HAN^1,#, WENFENG LUO¹, JIAN SHEN¹, JINGGENG LUO², XINGKUI TANG², TING PANG¹, YUBING LV¹, JIABING LIANG¹, LIYIN LIAO¹, HAOYU ZHANG¹, YONG JIANG¹, YUGUANG LI^3,*, JINHUA HE^1,*

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 molecules, and extracellular matrix. A… More >

BIN ZHANG^1,#, JIANYI ZHAO^3,#, YONGZHI WANG^2,#, HUA XU¹, BO GAO¹, GUANGNING ZHANG¹, BIN HAN¹, GUOHONG SONG¹, JUNCHEN ZHANG^1,*, WEI MENG^1,*

Oncology Research, Vol.31, No.6, pp. 917-927, 2023, DOI:10.32604/or.2023.030425

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 database. Knockdown of CHRM3 inhibited… More >

MUNEEBA MALIK¹, MAMOONA MAQBOOL², TOOBA NISAR³, TAZEEM AKHTER⁴, JAVED AHMED UJAN^5,6, ALANOOD S. ALGARNI⁷, FAKHRIA A. AL JOUFI⁸, SULTAN SHAFI K. ALANAZI⁹, MOHAMMAD HADI ALMOTARED¹⁰, MOUNIR M. SALEM BEKHIT¹¹, MUHAMMAD JAMIL^12,*

Oncology Research, Vol.31, No.6, pp. 899-916, 2023, DOI:10.32604/or.2023.030760

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 retrieved were analyzed… More >

EFFAT ALEMZADEH¹, LEILA ALLAHQOLI², HAMIDEH DEHGHAN³, AFROOZ MAZIDIMORADI⁴, ALIREZA GHASEMPOUR³, HAMID SALEHINIYA^5,*

Oncology Research, Vol.31, No.5, pp. 667-675, 2023, DOI:10.32604/or.2023.028406

Abstract Liquid biopsy, including both circulating tumor cells and circulating tumor DNA, is becoming more popular as a diagnostic tool in the clinical management of breast cancer. Elevated concentrations of these biomarkers during cancer treatment may be used as markers for cancer progression as well as to understand the mechanisms underlying metastasis and treatment resistance. Thus, these circulating markers serve as tools for cancer assessing and monitoring through a simple, non-invasive blood draw. However, despite several study results currently noting a potential clinical impact of ctDNA mutation tracking, the method is not used clinically in cancer diagnosis among patients and more… More > Graphic Abstract

SUKRAN SENYUREK¹, SEZER SAGLAM^2,*, ESRA KAYTAN SAGLAM³, HAKAN YANAR⁴, KAAN GOK⁴, DIDEM TASTEKIN⁵, CANAN KOKSAL AKBAS⁶, NERGIZ DAGOGLU SAKIN³, GULBIZ DAGOGLU KARTAL⁷, EMRE BALIK⁸, METIN KESKIN⁴, YASEMIN SANLI⁹, MINE GULLUOGLU¹⁰, ZULEYHA AKGUN¹¹

Oncology Research, Vol.31, No.5, pp. 689-696, 2023, DOI:10.32604/or.2023.030351

Abstract Radiation therapy (RT) is typically applied using one of two standard approaches for preoperative treatment of resectable locally advanced rectal cancer (LARC): short-course RT (SC-RT) alone or long-course RT (LC-RT) with concurrent fluorouracil (5-FU) chemotherapy. The Phase II single-arm KROG 11-02 study using intermediate-course (IC) (33 Gy (Gray)/10 fr (fraction) with concurrent capecitabine) preoperative chemoradiotherapy (CRT) demonstrated a pathologically complete response rate and a sphincter-sparing rate that were close to those of LC-CRT. The current trial aim to compare the pathological/oncological outcomes, toxicity, and quality of life results of LC-CRT and IC-CRT in cases of LARC. The prescribed dose was… More >

ZIYU LIU^1,2, AKIKO OKANO^3,4, EMIKO SANADA^1,3,4, YUSHI FUTAMURA^3,4, TOSHIHIKO NOGAWA^3,5, KOSUKE ISHIKAWA⁶, KENTARO SEMBA^7,8, JIANG LI⁹, XIAOMENG LI¹⁰, HIROYUKI OSADA^3,4,11,*, NOBUMOTO WATANABE^1,2,4,*

Oncology Research, Vol.31, No.5, pp. 655-666, 2023, DOI:10.32604/or.2023.030248

Abstract

Myc belongs to a family of proto-oncogenes that encode transcription factors. The overexpression of c-Myc causes many types of cancers. Recently, we established a system for screening c-Myc inhibitors and identified antimycin A by screening the RIKEN NPDepo chemical library. The specific mechanism of promoting tumor cell metastasis by high c-Myc expression remains to be explained. In this study, we screened approximately 5,600 microbial extracts using this system and identified a broth prepared from Streptomyces sp. RK19-A0402 strongly inhibits c-Myc transcriptional activity. After purification of the hit broth, we identified compounds closely related to the aglycone of cytovaricin and had… More > Graphic Abstract

XINTONG LIU^1,2,3, EMIKO SANADA^1,3,4, JIANG LI⁵, XIAOMENG LI⁶, HIROYUKI OSADA^1,4,7,*, NOBUMOTO WATANABE^1,2,3,*

Oncology Research, Vol.31, No.5, pp. 645-654, 2023, DOI:10.32604/or.2023.030240

Abstract β-transducin repeat-containing protein (β-TrCP) is an F-box protein subunit of the E3 Skp1-Cullin-F box (SCF) type ubiquitin-ligase complex, and provides the substrate specificity for the ligase. To find potent ligands of β-TrCP useful for the proteolysis targeting chimera (PROTAC) system using β-TrCP in the future, we developed a high-throughput screening system for small molecule β-TrCP ligands. We screened the chemical library utilizing the system and obtained several hit compounds. The effects of the hit compounds on in vitro ubiquitination activity of SCF^β-TrCP1 and on downstream signaling pathways were examined. Hit compounds NPD5943, NPL62020-01, and NPL42040-01 inhibited the TNFα-induced degradation of… More > Graphic Abstract