keyword
https://read.qxmd.com/read/38534772/5-aza-upregulates-socs3-and-ptpn6-shp1-inhibiting-stat3-and-potentiating-the-effects-of-ag490-against-primary-effusion-lymphoma-cells
#1
JOURNAL ARTICLE
Michele Di Crosta, Andrea Arena, Rossella Benedetti, Maria Saveria Gilardini Montani, Mara Cirone
Epigenetic modifications, including aberrant DNA methylation occurring at the promoters of oncogenes and oncosuppressor genes and histone modifications, can contribute to carcinogenesis. Aberrant methylation mediated by histone methylatransferases, alongside histones, can affect methylation of proteins involved in the regulation of pro-survival pathways such as JAK/STAT and contribute to their activation. In this study, we used DNA or histone demethylating agents, 5-Azacytidine (5-AZA) or DS-3201 (valemetostat), respectively, to treat primary effusion lymphoma (PEL) cells, alone or in combination with AG490, a Signal transducer and activator of transcription 3 (STAT3) inhibitor...
March 14, 2024: Current Issues in Molecular Biology
https://read.qxmd.com/read/38521003/concurrent-inhibition-of-alk-and-src-kinases-disrupts-the-alk-lung-tumor-cell-proteome
#2
JOURNAL ARTICLE
Alberto Diaz-Jimenez, Maria Ramos, Barbara Helm, Sara Chocarro, Dario Lucas Frey, Shubham Agrawal, Kalman Somogyi, Ursula Klingmüller, Junyan Lu, Rocio Sotillo
Precision oncology has revolutionized the treatment of ALK-positive lung cancer with targeted therapies. However, an unmet clinical need still to address is the treatment of refractory tumors that contain drug-induced resistant mutations in the driver oncogene or exhibit resistance through the activation of diverse mechanisms. In this study, we established mouse tumor-derived cell models representing the two most prevalent EML4-ALK variants in human lung adenocarcinomas and characterized their proteomic profiles to gain insights into the underlying resistance mechanisms...
March 19, 2024: Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
https://read.qxmd.com/read/38515732/efficacy-and-potential-mechanism-of-atherosclerosis-prevention-by-the-active-components-of-leech-based-on-network-pharmacology-combined-with-animal-experiments
#3
JOURNAL ARTICLE
Qing Lv, Mengyi Li, Ziyun Wen, Qianqian Han, Liang Wei, Jisheng Chen, Yunyun Pan
INTRODUCTION: Leeches are flesh-eating and bloodsucking parasitic worms. They are being used as a traditional Chinese medicine for centuries in activating blood and dissolving statis, dreging the meridims and tick. Hirudin, an active peptide product present in leech, has blood anticoagulant property and can assist in the treatment of thrombosis and diseases related to blood circulation. The efficacy and potential mechanism of action of leeches in such diseases should be further explored...
March 30, 2024: Heliyon
https://read.qxmd.com/read/38513196/discovery-of-a-covalent-inhibitor-selectively-targeting-the-autophosphorylation-site-of-c-src-kinase
#4
JOURNAL ARTICLE
Huimin Zhang, Dounan Xu, Hongchan Huang, Hao Jiang, Linghao Hu, Liping Liu, Ge Sun, Jing Gao, Yuanqing Li, Cuicui Xia, Shijie Chen, Hu Zhou, Xiangqian Kong, Mingliang Wang, Cheng Luo
Nonreceptor tyrosine kinase c-Src plays a crucial role in cell signaling and contributes to tumor progression. However, the development of selective c-Src inhibitors turns out to be challenging. In our previous study, we performed posttranslational modification-inspired drug design (PTMI-DD) to provide a plausible way for designing selective kinase inhibitors. In this study, after identifying a unique pocket comprising a less conserved cysteine and an autophosphorylation site in c-Src as well as a promiscuous covalent inhibitor, chemical optimization was performed to obtain ( R )-LW-Srci-8 with nearly 75-fold improved potency (IC50 = 35...
March 21, 2024: ACS Chemical Biology
https://read.qxmd.com/read/38507738/in-btk-phosphorylated-y223-in-the-sh3-domain-mirrors-catalytic-activity-but-does-not-influence-biological-function
#5
JOURNAL ARTICLE
Hernando Yesid Estupiñan Velasquez, Thibault Bouderlique, Chenfei He, Anna Berglöf, Andrea Cappelleri, Nicolai Frengen, Rula Zain, Mikael C I Karlsson, Robert Månsson, C I Edvard Smith
Bruton's tyrosine kinase (BTK) is an enzyme needed for B-cell survival and inhibitors have become potent targeted medicines for the treatment of B-cell malignancies. The initial activation event of cytoplasmic protein-tyrosine kinases is the phosphorylation of a conserved regulatory tyrosine in the catalytic domain, which in BTK is represented by tyrosine 551. In addition, the tyrosine 223 (Y223) residue in the SRC homology 3 (SH3) domain has for more than two decades generally been considered necessary for full enzymatic activity...
March 20, 2024: Blood Advances
https://read.qxmd.com/read/38507464/egfr-amplification-and-egfrviii-predict-and-participate-in-tat-cx43266-283-antitumor-response-in-preclinical-glioblastoma-models
#6
JOURNAL ARTICLE
Andrea Álvarez-Vázquez, Laura San-Segundo, Pilar Cerveró-García, Raquel Flores-Hernández, Claudia Ollauri-Ibáñez, Berta Segura-Collar, C G Hubert, Gillian Morrison, Steven M Pollard, Justin D Lathia, Pilar Sánchez-Gómez, Arantxa Tabernero
BACKGROUND: Glioblastoma (GBM) commonly displays epidermal growth factor receptor (EGFR) alterations (mainly amplification and EGFRvIII) and TAT-Cx43266-283 is a Src-inhibitory peptide with antitumor properties in preclinical GBM models. Given the link between EGFR and Src, the aim of this study was to explore the role of EGFR in the antitumor effects of TAT-Cx43266-283. METHODS: The effect of TAT-Cx43266-283, temozolomide (TMZ) and erlotinib (EGFR inhibitor) was studied in patient-derived GBM stem cells (GSCs) and murine neural stem cells (NSCs) with and without EGFR alterations, in vitro and in vivo...
March 20, 2024: Neuro-oncology
https://read.qxmd.com/read/38504984/tyrosine-phosphatase-ptpn11-shp2-in-solid-tumors-bull-s-eye-for-targeted-therapy
#7
REVIEW
Xun Chen, Steffen Johannes Keller, Philipp Hafner, Asma Y Alrawashdeh, Thomas Yul Avery, Johana Norona, Jinxue Zhou, Dietrich Alexander Ruess
Encoded by PTPN11 , the Src-homology 2 domain-containing phosphatase 2 (SHP2) integrates signals from various membrane-bound receptors such as receptor tyrosine kinases (RTKs), cytokine and integrin receptors and thereby promotes cell survival and proliferation. Activating mutations in the PTPN11 gene may trigger signaling pathways leading to the development of hematological malignancies, but are rarely found in solid tumors. Yet, aberrant SHP2 expression or activation has implications in the development, progression and metastasis of many solid tumor entities...
2024: Frontiers in Immunology
https://read.qxmd.com/read/38483999/distinct-early-role-of-pten-regulation-during-hcmv-infection-of-monocytes
#8
JOURNAL ARTICLE
Liudmila S Chesnokova, Bailey S Mosher, Heather L Fulkerson, Hyung W Nam, Akhalesh K Shakya, Andrew D Yurochko
Human cytomegalovirus (HCMV) infection of monocytes is essential for viral dissemination and persistence. We previously identified that HCMV entry/internalization and subsequent productive infection of this clinically relevant cell type is distinct when compared to other infected cells. We showed that internalization and productive infection required activation of epidermal growth factor receptor (EGFR) and integrin/c-Src, via binding of viral glycoprotein B to EGFR, and the pentamer complex to β1/β3 integrins...
March 19, 2024: Proceedings of the National Academy of Sciences of the United States of America
https://read.qxmd.com/read/38483947/deficiency-of-nuclear-receptor-coactivator-3-aggravates-diabetic-kidney-disease-by-impairing-podocyte-autophagy
#9
JOURNAL ARTICLE
Yaru Xie, Qian Yuan, Xinyi Cao, Yang Qiu, Jieyu Zeng, Yiling Cao, Yajuan Xie, Xianfang Meng, Kun Huang, Fan Yi, Chun Zhang
Nuclear receptors (NRs) are important transcriptional factors that mediate autophagy, preventing podocyte injury and the progression of diabetic kidney disease (DKD). However, the role of nuclear receptor coactivators that are powerful enhancers for the transcriptional activity of NRs in DKD remains unclear. In this study, a significant decrease in Nuclear Receptor Coactivator 3 (NCOA3) is observed in injured podocytes caused by high glucose treatment. Additionally, NCOA3 overexpression counteracts podocyte damage by improving autophagy...
March 14, 2024: Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
https://read.qxmd.com/read/38474118/pha-665752-s-antigrowth-and-proapoptotic-effects-on-hsc-3-human-oral-cancer-cells
#10
JOURNAL ARTICLE
Anil Kumar Yadav, Saini Wang, Young-Min Shin, Byeong-Churl Jang
c-Met is a tyrosine-kinase receptor, and its aberrant activation plays critical roles in tumorigenesis, invasion, and metastatic spread in many human tumors. PHA-665752 (PHA) is an inhibitor of c-Met and has antitumor effects on many hematological malignancies and solid cancers. However, the activation and expression of c-Met and its role and the antitumor effect of PHA on human oral squamous cell carcinoma (OSCC) cells remain unclear. Here, we investigated the activation and expression of c-Met and the effects of PHA on the growth of a highly tumorigenic HSC-3 human OSCC cell line with high c-Met phosphorylation and expression...
March 1, 2024: International Journal of Molecular Sciences
https://read.qxmd.com/read/38458013/inhibition-of-ptpre-suppresses-tumor-progression-and-improves-sorafenib-response-in-hepatocellular-carcinoma
#11
JOURNAL ARTICLE
Renshun Dong, Tianci Wang, Wei Dong, He Zhu, Qiumeng Liu, Huifang Liang, Xiaoping Chen, Bixiang Zhang, Xuewu Zhang
Hepatocellular carcinoma (HCC) has a poor prognosis, and the efficacy of current therapeutic strategies is extremely limited in advanced diseases. Our previous study reported that protein tyrosine phosphatase receptor epsilon (PTPRE) is a promoting factor in HCC progression. In this study, our objective was to evaluate the treatment effect of PTPRE inhibitors in different HCC preclinical models. Our results indicated that the PTPRE inhibitory compound 63 (Cpd-63) inhibited tumor cell proliferation, migration, and HCC organoid growth...
March 7, 2024: Biomedicine & Pharmacotherapy
https://read.qxmd.com/read/38454120/the-dual-hck-btk-inhibitor-kin-8194-impairs-growth-and-integrin-mediated-adhesion-of-btki-resistant-mantle-cell-lymphoma
#12
JOURNAL ARTICLE
Hildo C Lantermans, Fangxue Ma, Annemieke Kuil, Sanne van Kesteren, Sevtap Yasinoglu, Guang Yang, Sara J Buhrlage, Jinhua Wang, Nathanael S Gray, Marie José Kersten, Steven P Treon, Steven T Pals, Marcel Spaargaren
Although Bruton's tyrosine kinase (BTK) inhibitors (BTKi) have significantly improved patient prognosis, mantle cell lymphoma (MCL) is still considered incurable due to primary and acquired resistance. We have recently shown that aberrant expression of the Src-family tyrosine kinase hematopoietic cell kinase (HCK) in MCL correlates with poor prognosis, and that genetic HCK perturbation impairs growth and integrin-mediated adhesion of MCL cells. Here, we show that KIN-8194, a dual inhibitor of BTK and HCK with in vivo activity against Myd88-L265P-driven diffuse large B-cell lymphoma and Waldenström Macroglobulinemia, has a potent growth inhibitory effect in MCL cell lines and primary MCL cells, irrespective of their sensitivity to BTKi (ibrutinib and acalabrutinib)...
March 7, 2024: Leukemia
https://read.qxmd.com/read/38451719/phase-separation-of-shp2e76k-promotes-malignant-transformation-of-mesenchymal-stem-cells-by-activating-mitochondrial-complexes
#13
JOURNAL ARTICLE
Chen Kan, Zhenya Tan, Liwei Liu, Bo Liu, Li Zhan, Jicheng Zhu, Xiaofei Li, Keqiong Lin, Jia Liu, Yakun Liu, Fan Yang, Mandy Wong, Siying Wang, Hong Zheng
Mesenchymal stem cells, suffering from diverse gene hits, undergoes malignant transformation and aberrant osteochondral differentiation. Src homology region 2- (SH2-) containing protein tyrosine phosphatase 2 (SHP2), a non-receptor protein tyrosine phosphatase, regulates multicellular differentiation, proliferation, and transformation. However, the role of SHP2 in MSC fate determination remains unclear. Here, we showed that MSCs bearing the activating SHP2E76K mutation underwent malignant transformation into sarcoma stem-like cells (SSCs)...
March 7, 2024: JCI Insight
https://read.qxmd.com/read/38448751/prrx1-top2a-interaction-is-a-malignancy-promoting-factor-in-human-malignant-peripheral-nerve-sheath-tumours
#14
JOURNAL ARTICLE
Shota Takihira, Daisuke Yamada, Tatsunori Osone, Tomoka Takao, Masakiyo Sakaguchi, Michiyuki Hakozaki, Takuto Itano, Eiji Nakata, Tomohiro Fujiwara, Toshiyuki Kunisada, Toshifumi Ozaki, Takeshi Takarada
BACKGROUND: Paired related-homeobox 1 (PRRX1) is a transcription factor in the regulation of developmental morphogenetic processes. There is growing evidence that PRRX1 is highly expressed in certain cancers and is critically involved in human survival prognosis. However, the molecular mechanism of PRRX1 in cancer malignancy remains to be elucidated. METHODS: PRRX1 expression in human Malignant peripheral nerve sheath tumours (MPNSTs) samples was detected immunohistochemically to evaluate survival prognosis...
March 6, 2024: British Journal of Cancer
https://read.qxmd.com/read/38444386/hyperglycemic-stress-induces-oxidative-damage-of-enteric-glial-cells-by-triggering-redoxosomes-p66shc-activation
#15
JOURNAL ARTICLE
Yanmin Jiang, Lan Xu, Xue Zhu, Xiaowei Zhu, Xiang Xu, Jianbo Li
OBJECTIVES: Diabetic gastrointestinal dysfunction (DGD) is a serious complication of diabetic mellitus (DM), affecting the enteric nervous system (ENS), particular enteric glial cells (EGCs). This study aimed to elucidate the effects and underlying molecular mechanisms of hyperglycemic stress on EGCs in in vitro and in vivo models of DM. METHODS: In in vitro studies, enteric glial cell line CRL-2690 was exposed to hyperglycemia stress, and cell viability, cell apoptosis and oxidative damage were assessed...
December 2024: Redox Report: Communications in Free Radical Research
https://read.qxmd.com/read/38443724/yes1-as-a-potential-target-to-overcome-drug-resistance-in-egfr-deregulated-non-small-cell-lung-cancer
#16
JOURNAL ARTICLE
Eunjin Kook, JungYeol Lee, Do-Hee Kim
Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) such as gefitinib and osimertinib have primarily been used as first-line treatments for patients with EGFR-activating mutations in non-small cell lung cancer (NSCLC). Novel biomarkers are required to distinguish patients with lung cancer who are resistant to EGFR-TKIs. The aim of the study is to investigate the expression and functional role of YES1, one of the Src-family kinases, in EGFR-TKI-resistant NSCLC. YES1 expression was elevated in gefitinib-resistant HCC827 (HCC827/GR) cells, harboring EGFR mutations...
March 5, 2024: Archives of Toxicology
https://read.qxmd.com/read/38440826/protease-activated-receptor-2-drives-migration-in-a-colon-cancer-cell-line-but-not-in-non-cancerous-human-epithelial-cells
#17
JOURNAL ARTICLE
Larissa Lucena Périco, Andrew J Vegso, Cristiane H Baggio, Wallace K MacNaughton
The inflamed mucosa contains a complex assortment of proteases which may participate in wound healing or in the development of inflammation-associated colon cancer. We sought to determine the role of protease-activated receptor 2 (PAR2) in epithelial wound healing in both untransformed and transformed colonic epithelial cells. Monolayers of primary epithelial cells derived from organoids cultivated from patient colonic biopsies, and of the T84 colon cancer cell line, were grown to confluence, wounded in the presence of a selective PAR2-activating peptide, and healing visualized by live cell microscopy...
March 5, 2024: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://read.qxmd.com/read/38422592/n-and-s-substituted-pyrazolopyrimidines-a-promising-new-class-of-potent-c-src-kinase-inhibitors-with-prominent-antitumor-activity
#18
JOURNAL ARTICLE
Aeshah A Awaji, Waheed Ali Zaki El Zaloa, Mohamed A Seleem, Mohamed Alswah, Mohamed M Elsebaei, Ashraf H Bayoumi, Ahmed M El-Morsy, Mohammad Y Alfaifi, Ali A Shati, Serag Eldin I Elbehairi, Mohammed Almaghrabi, Ahmed K B Aljohani, Hany E A Ahmed
In this work, readily achievable synthetic pathways were utilized for construction of a library of N/S analogues based on the pyrazolopyrimidine scaffold with terminal alkyl or aryl fragments. Subsequently, we evaluated the anticancer effects of these novel analogs against the proliferation of various cancer cell lines, including breast, colon, and liver lines. The results were striking, most of the tested molecules exhibited strong and selective cytotoxic activity against the MDA-MB-231 cancer cell line; IC50 1...
February 21, 2024: Bioorganic Chemistry
https://read.qxmd.com/read/38415528/secretion-of-sphinganine-by-drug-induced-cancer-cells-and-modified-mimetic-sphinganine-mms-as-c-src-kinase-inhibitor
#19
JOURNAL ARTICLE
Raskia Nandangiri, Seethamma T N, Ajay Kumar Raj, Kiran B Lokhande, Kratika Khunteta, Ameya Hebale, Haet Kothari, Vaidehi Patel, Sachin C Sarode, Nilesh Kumar Sharma
BACKGROUND: Cancer cells exhibit selective metabolic reprogramming to promote proliferation, invasiveness, and metastasis. Sphingolipids such as sphingosine and sphinganine have been reported to modulate cell death processes in cancer cells. However, the potential of extracellular sphinganine and its mimetic compounds as inducers of cancer cell death has not been thoroughly investigated. METHODS: We obtained extracellular conditioned medium from HCT-116 cells treated with the previously reported anticancer composition, goat urine DMSO fraction (GUDF)...
February 1, 2024: Asian Pacific Journal of Cancer Prevention: APJCP
https://read.qxmd.com/read/38411951/sting-inhibition-alleviates-bone-resorption-in-apical-periodontitis
#20
JOURNAL ARTICLE
Han-Qing Mao, Lu Zhou, Jia-Qi Li, Yuan-Hao Wen, Zhi Chen, Lu Zhang
AIM: The goal of this study was to investigate the potential effects of an immunotherapeutic drug targeting STING to suppress the overreactive innate immune response and relieve the bone defect in apical periodontitis. METHODOLOGY: We established an apical periodontitis mouse model in Sting-/- and WT mice in vivo. The progression of apical periodontitis was analysed by micro-CT analysis and H&E staining. The expression level and localization of STING in F4/80+ cells were identified by IHC and immunofluorescence staining...
February 27, 2024: International Endodontic Journal
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