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MASANORI KAWANO, KAZUHIRO TANAKA^*, ICHIRO ITONAGA, TATSUYA IWASAKI, YUTA KUBOTA, HIROSHI TSUMURA
Oncology Research, Vol.31, No.5, pp. 631-643, 2023, DOI:10.32604/or.2023.029745
Abstract Heat shock protein (HSP) 90 plays a crucial role in correcting the misfolded three-dimensional structure of proteins, assisting them in folding into proper conformations. HSP90 is critical in maintaining the normal functions of various proteins within cells, as essential factors for cellular homeostasis. Contrastingly, HSP90 simultaneously supports the maturation of cancer-related proteins, including mesenchymal epithelial transition factor (MET) within tumor cells. All osteosarcoma cell lines had elevated MET expression in the cDNA array in our possession. MET, a tyrosine kinase receptor, promotes proliferation and an anti-apoptotic state through the activation of the MET pathway constructed by HSP90. In this study,… More >

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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
（This article belongs to the Special Issue: Approach from Chemical Biology for Cancer Research)
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 >

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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
（This article belongs to the Special Issue: Approach from Chemical Biology for Cancer Research)
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 >

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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 >

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MUHAMMAD BABAR KHAWAR^1,2,3,#, YAJUN WANG^4,#, ANEEQA MAJEED³, ALI AFZAL⁵, KABEER HANEEF⁶, HAIBO SUN^1,2,*
Oncology Research, Vol.31, No.5, pp. 677-688, 2023, DOI:10.32604/or.2023.029718
Abstract Hepatocellular carcinoma, the most common primary liver cancer and a leading cause of death, is a difficult disease to treat due to its heterogeneous nature. Traditional models, such as 2D culture and patient-derived xenografts, have not proven effective. However, the development of 3D culture techniques, such as organoids, which can mimic the tumor microenvironment (TME) and preserve heterogeneity and pathophysiological properties of tumor cells, offers new opportunities for treatment and research. Organoids also have the potential for biomarker detection and personalized medication, as well as genome editing using CRISPR/Cas9 to study the behavior of certain genes and therapeutic interventions. This… More >

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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 >

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XUEFENG WANG^1,#, SICONG JIANG^2,#, XINHONG ZHOU³, XIAOFENG WANG⁴, LAN LI⁵, JIANJUN TANG^1,*
Oncology Research, Vol.31, No.5, pp. 697-714, 2023, DOI:10.32604/or.2023.029458
（This article belongs to the Special Issue: Role of Reactive Oxygen Species and DNA Damage in Tumor Immunological Responses)
Abstract Background: Pancreatic cancer is associated with high mortality and is one of the most aggressive of malignancies, but studies have not fully evaluated its molecular subtypes, prognosis and response to immunotherapy of different subtypes. The purpose of this study was to explore the molecular subtypes and the key genes associated with the prognosis of pancreas cancer patients and study the clinical phenotype, prognosis and response to immunotherapy using single-cell seq data and bulk RNA seq data, and data retrieved from GEO and TCGA databases. Methods: Single-cell seq data and bioinformatics methods were used in this study. Pancreatic cancer data were… More >

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LIN QIU^1,#, ANQI TAO^1,#, XIAOQIAN SUN^4,5, FEI LIU¹, XIANPENG GE^2,3,*, CUIYING LI^1,*
Oncology Research, Vol.31, No.5, pp. 715-752, 2023, DOI:10.32604/or.2023.029443
Abstract We analyzed RNA-sequencing (RNA-seq) and clinical data from head and neck squamous cell carcinoma (HNSCC) patients in The Cancer Genome Atlas (TCGA) Genomic Data Commons (GDC) portal to investigate the prognostic value of anoikis-related genes (ARGs) in HNSCC and develop new targeted drugs. Differentially expressed ARGs were screened using bioinformatics methods; subsequently, a prognostic model including three ARGs (CDKN2A, BIRC5, and PLAU) was constructed. Our results showed that the model-based risk score was a good prognostic indicator, and the potential of the three ARGs in HNSCC prognosis was validated by the TISCH database, the model’s accuracy was validated in two… More >

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DONGJIE SUN^1,2, CHI ZHANG^3,*
Oncology Research, Vol.31, No.5, pp. 753-767, 2023, DOI:10.32604/or.2023.029287
Abstract Lung adenocarcinoma (LUAD) is the leading cause of cancer-related deaths, accounting for over a million deaths worldwide annually. Immunogenic cell death (ICD) elicits an adaptive immune response. However, the role of ICD-related long noncoding RNAs (lncRNAs) in LUAD is unknown. In this study, we investigated the characteristics of the tumor microenvironment in LUAD, the prognostic significance of ICD-related lncRNAs, and the half-maximal inhibitory concentration (IC50) of possible chemotherapeutic drugs. We sorted prognostic lncRNAs using univariate Cox regression and constructed a risk signature based on them. We then confirmed the model’s accuracy and generated a nomogram. Additionally, we performed immune microenvironment… More >

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TING ZHOU^1,#, PEIYING FU^1,#, DONG CHEN², RONGHUA LIU^1,*
Oncology Research, Vol.31, No.5, pp. 769-785, 2023, DOI:10.32604/or.2023.030166
（This article belongs to the Special Issue: Signaling Pathway Crosstalk in Malignant Tumors: Molecular Targets and Combinatorial Therapeutics)
Abstract Late-stage ovarian cancer (OC) has a poor prognosis and a high metastasis rate, but the underlying molecular mechanism is unclear. RNA binding proteins (RBPs) play important roles in posttranscriptional regulation in the contexts of neoplasia and tumor metastasis. In this study, we explored the molecular functions of a canonical RBP, Transformer 2β homolog (TRA2B), in cancer cells. TRA2B knockdown in HeLa cells and subsequent whole-transcriptome RNA sequencing (RNA-seq) analysis revealed the TRA2B-regulated alternative splicing (AS) profile. We disrupted TRA2B expression in epithelial OC cells and performed a series of experiments to confirm the resulting effects on OC cell proliferation, apoptosis… More >

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FENGXIANG TANG, YANSHI LI, MIN PAN, ZHIHAI WANG, TAO LU, CHUAN LIU, XIN ZHOU, GUOHUA HU^*
Oncology Research, Vol.31, No.5, pp. 787-803, 2023, DOI:10.32604/or.2023.030081
Abstract Background: Lymphatic metastasis (LM) emerges as an independent prognostic marker for hypopharyngeal squamous cell carcinoma (HSPSCC), chiefly contributing to treatment inefficacy. This study aimed to scrutinize the prognostic relevance of HSP90AA1 and its potential regulatory mechanism of concerning LM in HPSCC. Methods: In a preceding investigation, HSP90AA1, a differential gene, was discovered through transcriptome sequencing of HPSCC tissues, considering both the presence and absence of LM. Validation of HSP90AA1 expression was accomplished via qRT-PCR, western-blotting(WB), and immunohistochemistry(IHC), while its prognostic significance was assessed employing Kaplan–Meier survival analysis(KMSA), log-rank test(LR), and Cox’s regression analysis(CRA). Bioinformatics techniques facilitated the prediction and analysis… More >

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TIANYING CAI^1,2, JUNJIE BAI¹, PENG TAN³, ZHIWEI HUANG¹, CHEN LIU¹, ZIMING WU¹, YONGLANG CHENG¹, TONGXI LI¹, YIFAN CHEN¹, JIAN RUAN⁴, LIN GAO⁵, YICHAO DU^3,*, WENGUANG FU^1,3,*
Oncology Research, Vol.31, No.5, pp. 805-817, 2023, DOI:10.32604/or.2023.029549
Abstract Hepatocellular carcinoma (HCC) is a common malignancy that is driven by multiple genes and pathways. The aim of this study was to investigate the role and specific mechanism of the actin-interacting protein zyxin (ZYX) in HCC. We found that the expression of ZYX was significantly higher in HCC tissues compared to that in normal liver tissues. In addition, overexpression of ZYX in hepatoma cell lines (PLC/PRF/5, HCCLM3) enhanced their proliferation, migration and invasion, whereas ZYX knockdown had the opposite effects (SK HEP-1, Huh-7). Furthermore, the change in the expression levels of ZYX also altered that of proteins related to cell… More >

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WENHAO XU^1,#, HAOMING LI^2,#, YASIR HAMEED³, MOSTAFA A. ABDEL-MAKSOUD⁴, SAEEDAH MUSAED ALMUTAIRI⁴, AYMAN MUBARAK⁴, MOHAMMED AUFY⁵, WAEL ALTURAIKI⁶, ABDULAZIZ J. ALSHALANI⁶, AYMAN M. MAHMOUD^7,*, CHEN LI^8,*
Oncology Research, Vol.31, No.5, pp. 819-831, 2023, DOI:10.32604/or.2023.029414
（This article belongs to the Special Issue: Cancer Metastasis)
Abstract N6-methyladenosine methylation (m6A) is a common type of epigenetic alteration that prominently affects the prognosis of tumor patients. However, it is unknown how the m6A regulator affects the tumor microenvironment (TME) cell infiltration in adrenocortical carcinoma (ACC) and how it affects the prognosis of ACC patients yet. The m6A alteration patterns of 112 ACC patients were evaluated, furthermore, the association with immune infiltration cell features was investigated. The unsupervised clustering method was applied to typify the m6A alteration patterns of ACC patients. The principal component analysis (PCA) technique was taken to create the m6A score to assess the alteration pattern… More >

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