keyword
https://read.qxmd.com/read/38528516/peli1-key-players-in-the-oncogenic-characteristics-of-pancreatic-cancer
#1
JOURNAL ARTICLE
Xiaobin Fei, Changhao Zhu, Peng Liu, Songbai Liu, Likun Ren, Rishang Lu, Junyi Hou, Yongjia Gao, Xing Wang, Yaozhen Pan
BACKGROUND: Pancreatic cancer (PC) is a highly malignant gastrointestinal tumor, which is characterized by difficulties in early diagnosis, early metastasis, limited therapeutic response and a grim prognosis. Therefore, it is imperative to explore potential therapeutic targets for PC. Currently, although the involvement of the Pellino E3 Ubiquitin Protein Ligase 1 (PELI1) in the human growth of some malignant tumors has been demonstrated, its association with PC remains uncertain. METHODS: Bioinformatics, qRT-PCR, Western blot and IHC were used to detect the expression of PELI1 in pancreas or PC tissues and cells at mRNA and protein levels...
March 25, 2024: Journal of Experimental & Clinical Cancer Research: CR
https://read.qxmd.com/read/38523676/twenty-years-of-gendicine%C3%A2-rad-p53-cancer-gene-therapy-the-first-in-class-human-cancer-gene-therapy-in-the-era-of-personalized-oncology
#2
REVIEW
Li Qi, Guiqing Li, Peipei Li, Hongwei Wang, Xiaolong Fang, Tongchuan He, Jingjing Li
Genetic mutations in TP53 contribute to human malignancies through various means. To date, there have been a variety of therapeutic strategies targeting p53, including gene therapy to restore normal p53 function, mutant p53 rescue, inhibiting the MDM2-p53 interaction, p53-based vaccines, and a number of other approaches. This review focuses on the functions of TP53 and discusses the aberrant roles of mutant p53 in various types of cancer. Recombinant human p53 adenovirus, trademarked as Gendicine, which is the first anti-tumor gene therapy drug, has made tremendous progress in cancer gene therapy...
July 2024: Genes & Diseases
https://read.qxmd.com/read/38522240/an-anti-gd2-aptamer-based-bifunctional-spherical-nucleic-acid-nanoplatform-for-synergistic-therapy-targeting-mdm2-for-retinoblastoma
#3
JOURNAL ARTICLE
Shijing Wang, Yan Zhao, Fei Yao, Pengxue Wei, Lan Ma, Shaochong Zhang
Retinoblastoma (RB) is a type of pediatric solid tumor in the fundus. The lack of precision therapies combined with the difficulty of delivering small interfering RNA (siRNA) into the eyes means that there is currently no nucleic acid-based therapy for RB in clinical practice. Here, we reported on anti-GD2 and glutathione-responsive spherical nucleic acids (SNAs), loaded with siRNA and the inhibitor NVP-CGM097, which jointly blocked the oncogenic factor n in RB cells (Y79 and WERI-RB-1). The SNAs were formed through the self-assembly of bifunctional cholesterol amphiphiles containing aptamers that specifically targeted GD2-positive RB cells, allowing for the formation of an SNA with a dense DNA shell...
March 22, 2024: Biomedicine & Pharmacotherapy
https://read.qxmd.com/read/38519029/foxo1-promotes-cancer-cell-growth-through-mdm2-mediated-p53-degradation
#4
JOURNAL ARTICLE
Haruki Tomiyasu, Makoto Habara, Shunsuke Hanaki, Yuki Sato, Yosei Miki, Midori Shimada
FOXO1 is a transcription factor and potential tumor suppressor that is negatively regulated downstream of PI3K-PKB/AKT signaling. Paradoxically, FOXO also promotes tumor growth, but the detailed mechanisms behind this role of FOXO are not fully understood. In this study, we revealed a molecular cascade by which the Thr24 residue of FOXO1 is phosphorylated by AKT and is dephosphorylated by calcineurin, which is a Ca2+ -dependent protein phosphatase. Curiously, single nucleotide somatic mutations of FOXO1 in cancer occur frequently at and near Thr24...
March 20, 2024: Journal of Biological Chemistry
https://read.qxmd.com/read/38481290/p53-biology-and-reactivation-for-improved-therapy-in-mds-and-aml
#5
REVIEW
Joanna E Zawacka
Myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) originate from preleukemic hematopoietic conditions, such as clonal hematopoiesis of indeterminate potential (CHIP) or clonal cytopenia of undetermined significance (CCUS) and have variable outcomes despite the successful implementation of targeted therapies. The prognosis differs depending on the molecular subgroup. In patients with TP53 mutations, the most inferior outcomes across independent studies were observed. Myeloid malignancies with TP53 mutations have complex cytogenetics and extensive structural variants...
March 13, 2024: Biomarker Research
https://read.qxmd.com/read/38474404/alcohol-exposure-induces-nucleolar-stress-and-apoptosis-in-mouse-neural-stem-cells-and-late-term-fetal-brain
#6
JOURNAL ARTICLE
Yanping Huang, George R Flentke, Olivia C Rivera, Nipun Saini, Sandra M Mooney, Susan M Smith
Prenatal alcohol exposure (PAE) is a leading cause of neurodevelopmental disability through its induction of neuronal growth dysfunction through incompletely understood mechanisms. Ribosome biogenesis regulates cell cycle progression through p53 and the nucleolar cell stress response. Whether those processes are targeted by alcohol is unknown. Pregnant C57BL/6J mice received 3 g alcohol/kg daily at E8.5-E17.5. Transcriptome sequencing was performed on the E17.5 fetal cortex. Additionally, primary neural stem cells (NSCs) were isolated from the E14...
March 2, 2024: Cells
https://read.qxmd.com/read/38473360/jun-dimerization-protein-2-jdp2-increases-p53-transactivation-by-decreasing-mdm2
#7
JOURNAL ARTICLE
Kasey Price, William H Yang, Leticia Cardoso, Chiung-Min Wang, Richard H Yang, Wei-Hsiung Yang
The AP-1 protein complex primarily consists of several proteins from the c-Fos, c-Jun, activating transcription factor (ATF), and Jun dimerization protein (JDP) families. JDP2 has been shown to interact with the cAMP response element (CRE) site present in many cis-elements of downstream target genes. JDP2 has also demonstrates important roles in cell-cycle regulation, cancer development and progression, inhibition of adipocyte differentiation, and the regulation of antibacterial immunity and bone homeostasis...
February 29, 2024: Cancers
https://read.qxmd.com/read/38467824/low-grade-central-osteosarcoma-with-extraosseous-dedifferentiation-a-rare-case
#8
JOURNAL ARTICLE
Kengo Kawaguchi, Kenichi Kohashi, Koji Sagiyama, Mikiko Hashisako, Akira Nabeshima, Nokitaka Setsu, Makoto Endo, Takeshi Iwasaki, Yasuharu Nakashima, Yoshinao Oda
Low-grade central osteosarcoma (LGCOS), which arises from the intramedullary cavity of the metaphysis of long bones, occasionally exhibits extraosseous spread. Approximately 10-30% of patients with LGCOS exhibit dedifferentiation, but it is rare to experience a primary tumor with a dedifferentiated component. A 38-year-old female patient presented with right knee pain for two months. Imaging studies revealed a bone mass with extraosseous involvement. Wide resection was performed, and pathologic examination led to the diagnosis of LGCOS with a dedifferentiated extraosseous lesion...
March 11, 2024: Skeletal Radiology
https://read.qxmd.com/read/38434910/comparative-expression-analysis-of-tp53-tumor-suppressor-and-mdm2-oncogene-in-colorectal-adenocarcinoma
#9
JOURNAL ARTICLE
Athanasios Niotis, Dimitrios Dimitroulis, Despoina Spyropoulou, Evangelos Tsiambas, Helen Sarlanis, Dimitrios Davris, Evangelos Falidas, Nikolaos Kavantzas, Dimitrios Peschos, Loukas Manaios, Konstantinos C Konstantinidis
BACKGROUND/AIM: The tumor protein 53 (TP53) tumor suppressor protein (17p13.1) acts as a significant regulator for the cell cycle normal function. The gene is frequently mutated in colorectal adenocarcinoma (CRC) patients and is associated to poor prognosis and low response rates to chemo-targeted therapy. Our purpose was to correlate TP53 expression with Mouse Double Minute 2 Homolog (MDM2), a proto-oncogene (12q14.3) and a major negative regulator in the TP53-MDM2 auto-regulatory pathway...
2024: Cancer Diagn Progn
https://read.qxmd.com/read/38431053/icaritin-activates-p53-and-inhibits-aerobic-glycolysis-in-liver-cancer-cells
#10
JOURNAL ARTICLE
Xiangyang Zhou, Di Wu, Tian Mi, Ruohan Li, Tao Guo, Wenjuan Li
Metabolic reprogramming enables cancer cells to generate energy mainly through aerobic glycolysis, which is achieved by increasing the expression levels of glycolysis-related enzymes. Therefore, the development of drugs targeting aerobic glycolysis could be an effective strategy for cancer treatment. Icaritin (ICT) is an active ingredient from the Chinese herbal plant Epimedium with several biological activities, but its anti-cancer mechanism remains inconclusive. Using normal hepatocytes and hepatoma cells, our results showed that ICT suppressed cell proliferation and clonal formation and decreased glucose consumption and lactate production in liver cancer cells...
February 29, 2024: Chemico-biological Interactions
https://read.qxmd.com/read/38426258/a-common-cellular-response-to-broad-splicing-perturbations-is-characterized-by-metabolic-transcript-downregulation-driven-by-the-mdm2-p53-axis
#11
JOURNAL ARTICLE
Jade E Varineau, Eliezer Calo
Disruptions in core cellular processes elicit stress responses that drive cell-state changes leading to organismal phenotypes. Perturbations in the splicing machinery cause widespread mis-splicing, resulting in p53-dependent cell-state changes that give rise to cell-type-specific phenotypes and disease. However, a unified framework for how cells respond to splicing perturbations, and how this response manifests itself in nuanced disease phenotypes, has yet to be established. Here, we show that a p53-stabilizing Mdm2 alternative splicing event and the resulting widespread downregulation of metabolic transcripts are common events that arise in response to various splicing perturbations in both cellular and organismal models...
February 1, 2024: Disease Models & Mechanisms
https://read.qxmd.com/read/38409361/bop1-contributes-to-the-activation-of-autophagy-in-polycystic-ovary-syndrome-via-nucleolar-stress-response
#12
JOURNAL ARTICLE
Rui Ji, Zhimo Zhang, Zhe Yang, Xin Chen, Tailang Yin, Jing Yang
Abnormal autophagy is one of the vital features in polycystic ovary syndrome (PCOS). However, the underlying molecular mechanisms remain unelucidated. In this study, we aimed to investigate whether Block of Proliferation 1 (BOP1) is involved in the onset of autophagy activation of granulosa cells in PCOS. Firstly, we found that BOP1 expression was significantly down-regulated in the ovaries of PCOS mice, which was associated with the development of PCOS. Next, local injection of lentiviral vectors in the ovary for the overexpression of BOP1 significantly alleviated the phenotypes of elevated androgens, disturbed estrous cycle, and abnormal follicular development in PCOS mice...
February 27, 2024: Cellular and Molecular Life Sciences: CMLS
https://read.qxmd.com/read/38404269/-investigation-on-the-signaling-pathways-in-the-mechanism-of-hyperoxia-induced-acute-lung-injury-based-on-transcriptomics-sequencing
#13
JOURNAL ARTICLE
Song Qin, Xiaoqin Wang, Yingcong Ren, Banghai Feng, Junya Liu, Hong Yu, Jie Zheng, Huajun Chen, Zhouxiong Xing, Hong Mei
OBJECTIVE: To observe and verify the changes of transcriptome in hyperoxia-induced acute lung injury (HALI), and to further clarify the changes of pathways in HALI. METHODS: Twelve healthy male C57BL/6J mice were randomly divided into normoxia group and HALI group according to the random number table, with 6 mice in each group. The mice in the normoxia group were fed normally in the room, and the mice in the HALI group was exposed to 95% oxygen to reproduce the HALI animal model...
January 2024: Zhonghua Wei Zhong Bing Ji Jiu Yi Xue
https://read.qxmd.com/read/38401716/ddit3-amplified-or-low-polysomic-pleomorphic-sarcomas-without-mdm2-amplification-clinicopathological-review-and-immunohistochemical-profile-of-nine-cases
#14
JOURNAL ARTICLE
Taro Mori, Takeshi Iwasaki, Hiroki Sonoda, Kengo Kawaguchi, Takumi Tomonaga, Hiroshi Furukawa, Chiaki Sato, Sakura Shiraishi, Kenichi Taguchi, Sadafumi Tamiya, Reiko Yoneda, Yumi Oshiro, Tomoya Matsunobu, Chie Abe, Yusuke Kuboyama, Nozomi Ueki, Kenichi Kohashi, Hidetaka Yamamoto, Yasuharu Nakashima, Yoshinao Oda
Several high-grade pleomorphic sarcoma cases that cannot be classified into any existing established categories have been reported. These cases were provisionally classified into undifferentiated pleomorphic sarcoma (UPS). Some dedifferentiated liposarcoma (DDLS) cases may also have been classified into the UPS category due to the absence of MDM2 amplification or an atypical lipomatous tumor/well-differentiated liposarcoma component. We retrieved and reviewed 77 high-grade pleomorphic sarcoma cases, initially diagnosed as UPS in 66 cases and DDLS in 11 cases...
February 22, 2024: Human Pathology
https://read.qxmd.com/read/38398498/current-status-of-novel-multifunctional-targeted-pt-iv-compounds-and-their-reductive-release-properties
#15
REVIEW
Lingwen Xu, Xiangyu Kong, Xinzhi Li, Bin Zhang, Yuxiao Deng, Jinhu Wang, Chonggang Duan, Daizhou Zhang, Wentao Liu
Platinum-based drugs are widely used in chemotherapy for various types of cancer and are considered crucial. Tetravalent platinum (Pt(IV)) compounds have gained significant attention and have been extensively researched among these drugs. Traditionally, Pt(IV) compounds are reduced to divalent platinum (Pt(II)) after entering cells, causing DNA lesions and exhibiting their anti-tumor effect. However, the available evidence indicates that some Pt(IV) derivatives may differ from the traditional mechanism and exert their anti-tumor effect through their overall structure...
February 6, 2024: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://read.qxmd.com/read/38396916/association-of-mdm2-overexpression-in-ameloblastomas-with-mdm2-amplification-and-braf-v600e-expression
#16
JOURNAL ARTICLE
Konstantinos I Tosios, Eleni-Marina Kalogirou, Ioannis G Koutlas
Ameloblastoma is a rare tumor but represents the most common odontogenic neoplasm. It is localized in the jaws and, although it is a benign, slow-growing tumor, it has an aggressive local behavior and high recurrence rate. Therefore, alternative treatment options or complementary to surgery have been evaluated, with the most promising one among them being a targeted therapy with the v-Raf murine sarcoma viral oncogene homologue B ( BRAF ), as in ameloblastoma the activating mutation V600E in BRAF is common...
February 13, 2024: International Journal of Molecular Sciences
https://read.qxmd.com/read/38390263/inhibition-of-oct4-binding-at-the-mycn-locus-induces-neuroblastoma-cell-death-accompanied-by-downregulation-of-transcripts-with-high-open-reading-frame-dominance
#17
JOURNAL ARTICLE
Kazuma Nakatani, Hiroyuki Kogashi, Takanori Miyamoto, Taiki Setoguchi, Tetsushi Sakuma, Kazuto Kugou, Yoshinori Hasegawa, Takashi Yamamoto, Yoshitaka Hippo, Yusuke Suenaga
Amplification of MYCN is observed in high-risk neuroblastomas (NBs) and is associated with a poor prognosis. MYCN expression is directly regulated by multiple transcription factors, including OCT4, MYCN, CTCF, and p53 in NB. Our previous study showed that inhibition of p53 binding at the MYCN locus induces NB cell death. However, it remains unclear whether inhibition of alternative transcription factor induces NB cell death. In this study, we revealed that the inhibition of OCT4 binding at the MYCN locus, a critical site for the human-specific OCT4-MYCN positive feedback loop, induces caspase-2-mediated cell death in MYCN -amplified NB...
2024: Frontiers in Oncology
https://read.qxmd.com/read/38361286/virtual-screening-of-natural-products-targeting-ubiquitin-specific-protease-7
#18
JOURNAL ARTICLE
Hongju Li, Yujie Sun, Hua Yin, Yuzhu Zhang, Junhong Yu, Ning Hou, Peng Wang, Huicong Liang, Aowei Xie, Xiaohong Wang, Jianjun Dong, Ximing Xu
Ubiquitin-specific protease 7 (USP7) is a promising prognostic and druggable target for cancer therapy. Inhibition of USP7 can activate the MDM2-P53 signaling pathway, thereby promoting cancer cell apoptosis. This study based on watvina molecular docking of virtual screening method and biological evaluation found the new USP7 inhibitors targeting catalytic active site. Three hits were screened from 3760 natural products and validated as USP7 inhibitors by enzymatic and kinetic assays. The IC50 values of scutellarein (Scu), semethylzeylastera (DML) and salvianolic acid C (SAC) were 3...
February 15, 2024: Journal of Biomolecular Structure & Dynamics
https://read.qxmd.com/read/38347776/targeting-ubiquitin-specific-protease-5-overcomes-chemoresistance-via-negatively-regulating-p53-in-gastric-cancer
#19
JOURNAL ARTICLE
Jing Song, Lei Liu, Fang Wang, Di Bao
BACKGROUND: Resistance to chemotherapy is a major obstacle in the clinical management of gastric cancer, and the mechanisms underlying chemoresistance remain largely unknown. AIMS: This study aimed to investigate the involvement of ubiquitin-specific protease 5 (USP5), a deubiquitinating enzyme, in gastric cancer chemoresistance Methods: USP5 expression was analyzed in fifty paired gastric cancer and adjacent normal tissues, chemo-sensitive and chemo-resistant gastric cancer lines using quantitative ELISA...
February 9, 2024: Current Molecular Medicine
https://read.qxmd.com/read/38342564/a-naturally-derived-small-molecule-compound-suppresses-tumor-growth-and-metastasis-in-mice-by-relieving-p53-dependent-repression-of-cdk2-rb-signaling-and-the-snail-driven-emt
#20
JOURNAL ARTICLE
Boxue Ren, Yang Li, Lei DI, Ranran Cheng, Lijuan Liu, Hongmei Li, Yi Li, Zhangrui Tang, Yongming Yan, Tao Lu, Rong Fu, Yongxian Cheng, Zhaoqiu Wu
The tumor suppressor protein p53 is central to cancer biology, with its pathway reactivation emerging as a promising therapeutic strategy in oncology. This study introduced LZ22, a novel compound that selectively inhibits the growth, migration, and metastasis of tumor cells expressing wild-type p53, demonstrating ineffectiveness in cells devoid of p53 or those expressing mutant p53. LZ22's mechanism of action involves a high-affinity interaction with the histidine-96 pocket of the MDM2 protein. This interaction disrupted the MDM2-p53 binding, consequently stabilizing p53 by shielding it from proteasomal degradation...
February 2024: Chinese Journal of Natural Medicines
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