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  • Open Access

    REVIEW

    Development of PROTACS degrading KRAS and SOS1

    GERHARD HAMILTON*, MARIE-THERESE EGGERSTORFER, SANDRA STICKLER

    Oncology Research, Vol.32, No.8, pp. 1257-1264, 2024, DOI:10.32604/or.2024.051653

    Abstract The Kirsten rat sarcoma virus—son of sevenless 1 (KRAS-SOS1) axis drives tumor growth preferentially in pancreatic, colon, and lung cancer. Now, KRAS G12C mutated tumors can be successfully treated with inhibitors that covalently block the cysteine of the switch II binding pocket of KRAS. However, the range of other KRAS mutations is not amenable to treatment and the G12C-directed agents Sotorasib and Adragrasib show a response rate of only approximately 40%, lasting for a mean period of 8 months. One approach to increase the efficacy of inhibitors is their inclusion into proteolysis-targeting chimeras (PROTACs), which… More > Graphic Abstract

    Development of PROTACS degrading KRAS and SOS1

  • Open Access

    ARTICLE

    Evolutionary Safe Padé Approximation Scheme for Dynamical Study of Nonlinear Cervical Human Papilloma Virus Infection Model

    Javaid Ali1, Armando Ciancio2, Kashif Ali Khan3, Nauman Raza4,5, Haci Mehmet Baskonus6,*, Muhammad Luqman1, Zafar-Ullah Khan7

    CMES-Computer Modeling in Engineering & Sciences, Vol.140, No.3, pp. 2275-2296, 2024, DOI:10.32604/cmes.2024.046923

    Abstract This study proposes a structure-preserving evolutionary framework to find a semi-analytical approximate solution for a nonlinear cervical cancer epidemic (CCE) model. The underlying CCE model lacks a closed-form exact solution. Numerical solutions obtained through traditional finite difference schemes do not ensure the preservation of the model’s necessary properties, such as positivity, boundedness, and feasibility. Therefore, the development of structure-preserving semi-analytical approaches is always necessary. This research introduces an intelligently supervised computational paradigm to solve the underlying CCE model’s physical properties by formulating an equivalent unconstrained optimization problem. Singularity-free safe Padé rational functions approximate the mathematical More >

  • Open Access

    ARTICLE

    Knockdown of HVEM, a Lymphocyte Regulator Gene, in Ovarian Cancer Cells Increases Sensitivity to Activated T Cells

    Ting Zhang1, Lei Ye1, Lingfei Han, Qizhi He, Jianlong Zhu

    Oncology Research, Vol.24, No.3, pp. 189-196, 2016, DOI:10.3727/096504016X14641336229602

    Abstract Ovarian cancer is highly malignant with a gradually increasing incidence and a high mortality rate. Immunosuppression is induced in ovarian cancer, although the mechanism detail is not clear. It has been indicated that HVEM (herpesvirus entry mediator) B- and T-lymphocyte attenuator (BTLA) negatively regulates the immune responses of T lymphocytes. Here, HVEM mRNA was found to be elevated in ovarian cancer tissue samples and primary ovarian cancer cells in comparison with benign tissue samples. We then knocked down HVEM expression in an ovarian cancer cell line, OVCAR3, by lentivirus-based small hairpin RNA (shRNA). Cell Counting… More >

  • Open Access

    ERRATUM

    Knockdown of HVEM, a Lymphocyte Regulator Gene, in Ovarian Cancer Cells Increases Sensitivity to Activated T Cells

    Ting Zhang1, Lei Ye1, Qizhi He, Jianlong Zhu

    Oncology Research, Vol.25, No.9, pp. 1665-1665, 2017, DOI:10.3727/096504017X15078984695565

    Abstract Ovarian cancer is highly malignant with a gradually increasing incidence and a high mortality rate. Immunosuppression is induced in ovarian cancer, although the mechanism detail is not clear. It has been indicated that HVEM (herpesvirus entry mediator) B- and T-lymphocyte attenuator (BTLA) negatively regulates the immune responses of T lymphocytes. Here, HVEM mRNA was found to be elevated in ovarian cancer tissue samples and primary ovarian cancer cells in comparison with benign tissue samples. We then knocked down HVEM expression in an ovarian cancer cell line, OVCAR3, by lentivirus-based small hairpin RNA (shRNA). Cell Counting… More >

  • Open Access

    ARTICLE

    Overexpression of Human Papillomavirus Type 16 Oncoproteins Enhances Epithelial–Mesenchymal Transition via STAT3 Signaling Pathway in Non-Small Cell Lung Cancer Cells

    Wenzhang Zhang*1, Xin Wu†1, Liang Hu*, Yuefan Ma*, Zihan Xiu*, Bingyu Huang*, Yun Feng*, Xudong Tang*†‡

    Oncology Research, Vol.25, No.5, pp. 843-852, 2017, DOI:10.3727/096504016X14813880882288

    Abstract The human papillomavirus (HPV) infection may be associated with the development and progression of nonsmall cell lung cancer (NSCLC). However, the role of HPV-16 oncoproteins in the development and progression of NSCLC is not completely clear. Epithelial–mesenchymal transition (EMT), a crucial step for invasion and metastasis, plays a key role in the development and progression of NSCLC. Here we explored the effect of HPV-16 oncoproteins on EMT and the underlying mechanisms. NSCLC cell lines, A549 and NCI-H460, were transiently transfected with the EGFP-N1-HPV-16 E6 or E7 plasmid. Real-time PCR and Western blot analysis were performed… More >

  • Open Access

    ARTICLE

    Truncated Bid Overexpression Induced by Recombinant Adenovirus Cre/LoxP System Suppresses the Tumorigenic Potential of CD133+ Ovarian Cancer Stem Cells

    Qifang Long*, Weipei Zhu*, Jundong Zhou, Jinchang Wu, Weixian Lu, Cui Zheng, Dongmei Zhou, Ling Yu, Ru Yang

    Oncology Research, Vol.25, No.4, pp. 595-603, 2017, DOI:10.3727/096504016X14765492198706

    Abstract Ovarian cancer is one of the most lethal malignant gynecologic tumors with a high relapse rate worldwide. Cancer stem cells (CSCs) have been identified in ovarian cancer and other malignant tumors as a small population of cells that are capable of self-renewal and multidifferentiation. CD133+ ovarian CSCs have been reported to be more tumorigenic and more resistant to chemotherapeutic treatment. Thus, CD133 has emerged as one of the most promising therapeutic markers for ovarian cancer treatment. In the current study, we constructed a recombinant adenovirus Cre/loxP regulation system to selectively introduce truncated Bid (tBid) expression specifically… More >

  • Open Access

    ARTICLE

    Suppression of Asparaginyl Endopeptidase Inhibits Polyomavirus Middle T Antigen-Induced Tumor Formation and Metastasis

    Cheng Xu*1, Lu Cao*1, Jianhua Liu†1, Zhongrun Qian, Yu Peng§, Wenjing Zhu§, Yongming Qiu, Yingying Lin‡¶

    Oncology Research, Vol.25, No.3, pp. 407-415, 2017, DOI:10.3727/096504016X14743350548249

    Abstract Elevated circulating asparaginyl endopeptidase (AEP), a novel lysosomal protease, has been found in breast cancer, and AEP is thus considered to be a prognostic factor in this disease. However, the pathological functions of circulating AEP in the development of breast cancer and the potential of AEP-targeted therapy remain unclear. We used MMTV-PyVmT transgenic mice, which spontaneously develop mammary tumors. Western blotting showed overexpression of AEP in both primary tumor tissue and lung metastases compared to their normal counterparts. Moreover, the concentration of circulating AEP gradually increased in the serum during the development of mammary tumors. More >

  • Open Access

    ARTICLE

    MicroRNA-379 Suppresses Cervical Cancer Cell Proliferation and Invasion by Directly Targeting V-crk Avian Sarcoma Virus CT10 Oncogene Homolog-Like (CRKL)

    Xi Shi*1, Xiao Xiao†1, Na Yuan*, Shili Zhang*, Fukang Yuan, Xiaohong Wang§

    Oncology Research, Vol.26, No.7, pp. 987-996, 2018, DOI:10.3727/096504017X15140534417184

    Abstract Cervical cancer is the fourth most common malignancy among females worldwide. MicroRNA-379 (miR-379) is aberrantly expressed in multiple human cancer types. However, the expression pattern, roles, and detailed regulatory mechanisms of miR-379 in cervical cancer remain unknown. In this study, we found that miR-379 expression was downregulated in cervical cancer tissues and cell lines. Low miR-379 expression was correlated with International Federation of Gynecology and Obstetrics (FIGO) stage, lymph node metastasis, and distant metastasis. Additionally, miR-379 overexpression suppressed the proliferation and invasion of cervical cancer cells. Furthermore, V-crk avian sarcoma virus CT10 oncogene homolog-like (CRKL) More >

  • Open Access

    ARTICLE

    The Epstein-Barr virus-miRNA-BART6-5p regulates TGF-β/SMAD4 pathway to induce glycolysis and enhance proliferation and metastasis of gastric cancer cells

    XUHUI ZHAO1,2, XIAOMIN HUANG1, CHUNYAN DANG2, XIA WANG1, YUJIAO QI3, HONGLING LI2,*

    Oncology Research, Vol.32, No.5, pp. 999-1009, 2024, DOI:10.32604/or.2024.046679

    Abstract Background: EBV-miR-BARTs exhibit significant relevance in epithelial tumors, particularly in EBV-associated gastric and nasopharyngeal cancers. However, their specific mechanisms in the initiation and progression of gastric cancer remain insufficiently explored. Material and Methods: Initially, EBV-miRNA-BART6-5p and its target gene SMAD4 expression were assessed in EBV-associated gastric cancer tissues and cell lines. Subsequent transfection induced overexpression of EBV-miRNA-BART6-5p in AGS and MKN-45, and downregulation in EBV-positive cells (SUN-719). The subsequent evaluation aimed to observe their impact on gastric cancer cell proliferation, migration, and glycolytic processes, with the TGF-β/SMAD4 signaling pathway value clarified using a TGF-β inhibitor. Results:More >

  • Open Access

    ARTICLE

    Gp78 regulates PMP22 and causes ER stress and autophagy in EV71-VP1-overexpressing mouse Schwann cells

    DANPING ZHU1,#, GUANGMING LIU1,#, KUAN FENG1, SUYUN LI1, DANDAN HU2, SIDA YANG3,*, PEIQING LI1,*

    BIOCELL, Vol.48, No.4, pp. 653-664, 2024, DOI:10.32604/biocell.2024.044856

    Abstract Background: During Enterovirus type 71 (EV71) infection, the structural viral protein 1 (VP1) activates endoplasmic reticulum (ER) stress associated with peripheral myelin protein 22 (PMP22) accumulation and induces autophagy. However, the specific mechanism behind this process remains elusive. Methods: In this research, we used the VP1-overexpressing mouse Schwann cells (SCs) models co-transfected with a PMP22 silencing or Autocrine motility factor receptor (AMFR/gp78) overexpressing vector to explore the regulation of gp78 on PMP22 and its relationship with autophagy and apoptosis. Results: The activity of gp78 could be influenced by EV71-VP1, leading to a decrease in the ubiquitination… More >

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