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Search results for: PTPN11

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#33661186   2021/03/01 To Up

Demonstrating the effect of SHP2 inhibitor on cervical squamous cell carcinoma from the perspective of ZAP70.

SHP2, encoded by the PTPN11 gene, plays an important role in regulating immune cell functions in tumor microenvironment. Several SHP2 inhibitors have entered the clinical trial stage, but cervical squamous cell carcinoma (CSCC) has not been included in the indications. In Tlymphocytes, SHP2 can promote the dephosphorylation of ZAP70 kinase in the T cell receptor signaling complex after recruitment to the PD-1 cytoplasmic tail. In this study, we used bioinformatics tools to confirm that ZAP70 has a widespread impact on the immunity of CSCC, which is closely related to the survival of CSCC. The effect of ZAP70 on the survival of cervical cancer may not depend on the structure or amplification, but on the enhancement of function. And we identified ZAP70 and PTPN11 protein-protein interactions. SHP2 inhibitor is worth to be studied in the treatment of CSCC.
Ming Gong, Peng Liu, Tianyu He, Miao Zhang, Guang Li

2131 related Products with: Demonstrating the effect of SHP2 inhibitor on cervical squamous cell carcinoma from the perspective of ZAP70.

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#33659784   // To Up

shp-2 gene knockout upregulates CAR-driven cytotoxicity of YT NK cells.

In Russia, cancer is the second leading cause of death following cardiovascular diseases. Adoptive transfer of NK cells is a promising approach to fight cancer; however, for their successful use in cancer treatment, it is necessary to ensure their robust accumulation at tumor foci, provide resistance to the immunosuppressive tumor microenvironment, and to engineer them with higher cytotoxic activity. NK lymphocytes are known to kill cancer cells expressing a number of stress ligands; and the balance of signals from inhibitory and activating receptors on the surface of the NK cell determines whether a cytotoxic reaction is triggered. We hypothesized that stronger cytotoxicity of NK cells could be achieved via gene editing aimed at enhancing the activating signaling cascades and/or weakening the inhibitory ones, thereby shifting the balance of signals towards NK cell activation and target cell lysis. Here, we took advantage of the CRISPR/Cas9 system to introduce mutations in the coding sequence of the shp-2 (PTPN11) gene encoding the signaling molecule of inhibitory pathways in NK cells. These shp-2 knock-out NK cells were additionally transduced to express a chimeric antigen receptor (CAR) that selectively recognized the antigen of interest on the target cell surface and generated an activating signal. We demonstrate that the combination of shp-2 gene knockout and CAR expression increases the cytotoxicity of effector NK-like YT cells against human prostate cancer cell line Du-145 with ectopic expression of PSMA protein, which is specifically targeted by the CAR.
V G Subrakova, S V Kulemzin, T N Belovezhets, A N Chikaev, N A Chikaev, O A Koval, A A Gorchakov, A V Taranin

1404 related Products with: shp-2 gene knockout upregulates CAR-driven cytotoxicity of YT NK cells.

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#33645091   // To Up

[Network pharmacology study of Yi medicine Jinweitai Capsules in treating gastrointestinal diseases].

The network pharmacology and molecular docking methods were used to explore the mechanism of Jinweitai Capsules in the treatment of acute and chronic gastritis, gastric and duodenal ulcers, and chronic colitis. The chemical components of herbs in Jinweitai Capsules were collected through TCMSP, CNKI and PubMed. Target prediction was performed through PubChem and SwissTargetPrediction databases; genes relating to acute and chronic gastritis, gastric and duodenal ulcers, chronic colitis were collected from OMIM database; potential targets of Jinweitai Capsules for relevant gastrointestinal diseases were obtained by Venny analysis; DAVID database was used to perform GO and KEGG enrichment analysis; protein interactions were obtained by STRING database and visua-lized by Cytoscape; AutoDockVina was used for molecular docking of AKT1, EGFR, PTPN11 and its reverse-selected chemical components. Potential mechanisms of Jinweitai Capsules in treating relevant gastrointestinal diseases were clarified according to the results of the docking. The results showed 86 potential active ingredients of Jinweitai Capsules and 268 potential targets for treatment of acute and chronic gastritis, gastric and duodenal ulcers, and chronic colitis. KEGG pathway enrichment analysis showed that 20 pathways relating to acute and chronic gastritis, gastric and duodenal ulcers, and chronic colitis mainly involved calcium signaling pathway and chemokine signaling pathway. Molecular docking showed a good binding activity between AKT1, EGFR, PTPN11 and its reverse screening chemical components. Jinweitai Capsules may exert an effect in the treatment of acute and chronic gastritis, gastric and duodenal ulcers, and chronic colitis by acting on AKT1, EGFR, PTPN11 and other targets in 15 signal pathways relating to cell inflammation and immunity, cell proliferation and apoptosis, Helicobacter pylori infection, and gastrointestinal tract.
Cai-Feng Li, Feng-Rong Zhang, Na Zhu, Jian-Zhi Cui, Shi-Huan Tang, Zhi-Yong Li

1449 related Products with: [Network pharmacology study of Yi medicine Jinweitai Capsules in treating gastrointestinal diseases].

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#33625084   2021/02/22 To Up

Therapy-related Myeloid Neoplasms in Children: A Single-institute Study.

Therapy-related myeloid neoplasm (t-MN) in the pediatric population is not well characterized. We studied 12 pediatric patients diagnosed with t-MN in our institution since 2006. The median age at the t-MN diagnoses was 14.8 years (range, 9 to 20 y). The primary malignancies included 9 solid tumors and 3 hematopoietic malignancies. Rhabdomyosarcoma (n=4) was the most common primary malignancy. Five of the 9 patients with solid tumors and all 3 patients with hematopoietic malignancies had primary neoplasms involving bone marrow. The median latency period was 5.2 years (range, 1.8 to 13.8 y). Thrombocytopenia was present in all patients at the t-MN diagnoses. Complete or partial monosomy of chromosome 5 or 7 were the 2 most common cytogenetic abnormalities. A quarter of patients demonstrated a genetic predisposition to t-MN: 1 with Li-Fraumeni syndrome with a germline TP53 R248Q mutation, 1 with Noonan syndrome with a somatic mutation (PTPN11 S502T), and 1 with a constitutive chromosomal translocation [t(X;9)(p22;q34)] and a germline TP53 L130V mutation. Outcomes remain poor. Two patients survived 3 and 5.1 years after hematopoietic stem cell transplantation.
Geling Li, Taylor Holly, David R Kelly, Vishnu Reddy, Fady M Mikhail, Andrew J Carroll, Matthew A Kutny

2995 related Products with: Therapy-related Myeloid Neoplasms in Children: A Single-institute Study.

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#33588036   2021/02/13 To Up

Transcriptome analysis reveals possible antitumor mechanism of Chlorella exopolysaccharide.

Microalgae, one of the most important classes of biomass producers, can produce exopolysaccharides similar to bacteria. The exopolysaccharide from Chlorella (CEPS) displays remarkable anticancer activity the mechanism of which remains to be elucidated. In this study, we analyzed the inhibitory effect of CEPS on the growth of HeLa cells. The results showed that CEPS inhibited the proliferation, decreased the viability, and changed the morphology of HeLa cells. Transcriptome analysis showed that 1894 genes were differentially expressed in the CEPS-treated group compared with the control group, including 1076 genes that were upregulated and 818 genes that were downregulated. The results of gene function enrichment analysis showed that the differentially expressed genes (DEGs) were significantly enriched in apoptosis and tumor-related biological processes and participated in several cancer and apoptosisrelated signaling pathways, including the MAPK signaling pathway, TNF signaling pathway, and the PI3K-Akt signaling pathway. The protein-protein interaction network identified 13 DEGs including PTPN11, RSAD2, ISG15, IFIT1, MX2, IFIT2, OASL, OAS1, JUN, OAS2, XAF1, ISG20, and IRF9 as hub genes. Our results suggest that CEPS is a promising therapeutic drug for the follow-up interventional therapy of cancer.
Run Zhong, Jie-Qiong Li, Si-Wei Wu, Xiu-Miao He, Jin-Cai Xuan, Han Long, Hong-Quan Liu

1931 related Products with: Transcriptome analysis reveals possible antitumor mechanism of Chlorella exopolysaccharide.

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#33577785   2021/02/11 To Up

Proteogenomic and metabolomic characterization of human glioblastoma.

Glioblastoma (GBM) is the most aggressive nervous system cancer. Understanding its molecular pathogenesis is crucial to improving diagnosis and treatment. Integrated analysis of genomic, proteomic, post-translational modification and metabolomic data on 99 treatment-naive GBMs provides insights to GBM biology. We identify key phosphorylation events (e.g., phosphorylated PTPN11 and PLCG1) as potential switches mediating oncogenic pathway activation, as well as potential targets for EGFR-, TP53-, and RB1-altered tumors. Immune subtypes with distinct immune cell types are discovered using bulk omics methodologies, validated by snRNA-seq, and correlated with specific expression and histone acetylation patterns. Histone H2B acetylation in classical-like and immune-low GBM is driven largely by BRDs, CREBBP, and EP300. Integrated metabolomic and proteomic data identify specific lipid distributions across subtypes and distinct global metabolic changes in IDH-mutated tumors. This work highlights biological relationships that could contribute to stratification of GBM patients for more effective treatment.
Liang-Bo Wang, Alla Karpova, Marina A Gritsenko, Jennifer E Kyle, Song Cao, Yize Li, Dmitry Rykunov, Antonio Colaprico, Joseph H Rothstein, Runyu Hong, Vasileios Stathias, MacIntosh Cornwell, Francesca Petralia, Yige Wu, Boris Reva, Karsten Krug, Pietro Pugliese, Emily Kawaler, Lindsey K Olsen, Wen-Wei Liang, Xiaoyu Song, Yongchao Dou, Michael C Wendl, Wagma Caravan, Wenke Liu, Daniel Cui Zhou, Jiayi Ji, Chia-Feng Tsai, Vladislav A Petyuk, Jamie Moon, Weiping Ma, Rosalie K Chu, Karl K Weitz, Ronald J Moore, Matthew E Monroe, Rui Zhao, Xiaolu Yang, Seungyeul Yoo, Azra Krek, Alexis Demopoulos, Houxiang Zhu, Matthew A Wyczalkowski, Joshua F McMichael, Brittany L Henderson, Caleb M Lindgren, Hannah Boekweg, Shuangjia Lu, Jessika Baral, Lijun Yao, Kelly G Stratton, Lisa M Bramer, Erika Zink, Sneha P Couvillion, Kent J Bloodsworth, Shankha Satpathy, Weiva Sieh, Simina M Boca, Stephan Schürer, Feng Chen, Maciej Wiznerowicz, Karen A Ketchum, Emily S Boja, Christopher R Kinsinger, Ana I Robles, Tara Hiltke, Mathangi Thiagarajan, Alexey I Nesvizhskii, Bing Zhang, D R Mani, Michele Ceccarelli, Xi S Chen, Sandra L Cottingham, Qing Kay Li, Albert H Kim, David Fenyö, Kelly V Ruggles, Henry Rodriguez, Mehdi Mesri, Samuel H Payne, Adam C Resnick, Pei Wang, Richard D Smith, Antonio Iavarone, Milan G Chheda, Jill S Barnholtz-Sloan, Karin D Rodland, Tao Liu, Li Ding,

2406 related Products with: Proteogenomic and metabolomic characterization of human glioblastoma.

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#33570629   // To Up

Real-life experience with CPX-351 and impact on the outcome of high-risk AML patients: a multicentric French cohort.

CPX-351 is a liposomal formulation of cytarabine and daunorubicin approved for the treatment of adults with newly diagnosed, therapy-related acute myeloid leukemia (t-AML) or AML with myelodysplasia-related changes (MRC-AML). We retrospectively analyzed the efficacy and safety of CPX-351 in a real-world setting in 103 patients from 12 French centers, including the evaluation of molecular abnormalities at baseline and minimal residual disease (MRD) in responding patients, compared with a historical data set from Bordeaux-Toulouse DATAML registry. A favorable safety profile was observed, with a low frequency of alopecia (11%) and gastrointestinal toxicity (50%). The overall response rate after induction was 59%, and MRD <10-3 was achieved in 57% of complete response (CR)/CR with incomplete hematological recovery (CRi) patients. Only the presence of mutated TP53 (P = .02) or PTPN11 (P = .004) predicted lower response in multivariate analysis. Interestingly, high-risk molecular prognosis subgroups defined by 2017 European LeukemiaNet risk stratification, including ASXL1 and RUNX1 mutations, were not associated with a significantly lower response rate using CPX-351. With a median follow-up of 8.6 months, median overall survival (OS) was 16.1 months. Thirty-six patients underwent allogeneic stem cell transplantation with a significantly longer median OS compared with nontransplanted patients (P < .001). In multivariate analyses, only spliceosome mutations were associated with better OS (P = .04). In comparison with intensive chemotherapy, there was no difference in OS for patients <60 years. These data confirm the efficacy and safety of CPX-351 in high-risk AML (t-AML and MRC-AML) in a real-life setting. CPX-351 is a treatment of choice for patients aged ≥60 years.
Edmond Chiche, Ramy Rahmé, Sarah Bertoli, Pierre-Yves Dumas, Jean-Baptiste Micol, Yosr Hicheri, Florence Pasquier, Pierre Peterlin, Patrice Chevallier, Xavier Thomas, Michael Loschi, Alexis Genthon, Ollivier Legrand, Mohamad Mohty, Emmanuel Raffoux, Patrick Auberger, Alexis Caulier, Magalie Joris, Caroline Bonmati, Gabrielle Roth-Guepin, Caroline Lejeune, Arnaud Pigneux, Norbert Vey, Christian Recher, Lionel Ades, Thomas Cluzeau

1175 related Products with: Real-life experience with CPX-351 and impact on the outcome of high-risk AML patients: a multicentric French cohort.

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