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Oncogenes and tumor suppressor genes
Published in A. R. Genazzani, Hormone Replacement Therapy and Cancer, 2020
S. Giordano, S. Corso, P. Conrotto
Many nuclear proto-oncogene proteins are induced when normal cells are stimulated to grow, indicating their direct role in growth control. Usually, on growth factor stimulation, the transcription is rapidly induced but the RNA is very unstable.
Antigenic Status of Trophoblast in Humans and Mice
Published in Gérard Chaouat, The Immunology of the Fetus, 2020
The M-CSF receptor is the protein product of the c-fms proto-oncogene and, indeed, all proto-oncogene proteins so far identified are expressed in the human placenta.20,44 The trophoblast-tumor analogy may be closer for extravillous cytotrophoblast in terms of proliferation, invasiveness, apparent expression of Class Hike MHC antigens, and proto-oncogene transcription. In contrast, oncofetal protein and growth factor receptor expression appears more restricted to syncytiotrophoblast. There have been reports of retrovirus-like particles and retrovirus-like RNA-directed DNA polymerase activity in normal human and primate trophoblast tissue,47-50 which appear to represent selective expression of an endogenous C-type viral component of the host genome. In addition, human syncytiotrophoblast antigens have been described which serologically cross-react with mammalian retroviral structural proteins.51-53 It is not surprising, therefore, that there have been reports of antibody responses to retroviral antigens occurring occasionally in pregnancy.54,55
The Rous Sarcoma Virus Oncogene and its Proto-Oncogene Counterpart
Published in Pimentel Enrique, Oncogenes, 2020
pp60v-src Is much more efficient in inducing experimental cell transformation than its normal cellular counterpart, pp60c-src, but the mechanisms responsible for this difference are not understood. Quantitative and/or quantitative differences between the viral and cellular oncogene proteins could explain the observed differences in transforming ability. A simple dosage phenomenon could be involved since the level of pp60c-src present in normal cells is much lower than the level of pp60v-src present in RSV-infected cells.137 By placing the v-src oncogene under the control of a regulatable promoter such as the LTR of MMTV and manipulating glucocorticoid concentrations it can be shown that there is a distinct threshold dose for v-src-induced cellular transformation.138
Heat shock protein 90 and inflammatory activity in newly onset Crohn’s disease
Published in Scandinavian Journal of Gastroenterology, 2018
Tore Grimstad, Ingeborg Kvivik, Jan Terje Kvaløy, Lars Aabakken, Roald Omdal
HSP90 is produced only after transactivation by heat shock factors (HSFs), such as HSF1. Following exposure to stressors (e.g., inflammation, unfolded proteins or oxidative stress), HSF1 is released, enters the cell nucleus, undergoes chemical transformation and binds to specific DNA sequences, which activates transcription of HSP genes, including HSP70 and HSP90 [17]. HSP90 has effects on inflammation, cell differentiation and growth, wound healing, survival and apoptosis [7,17,18]. HSP90 can also stabilise oncogene proteins, and thus represents a potential target for anticancer therapies. Since HSP90 is involved in both innate and adaptive immunity, several preclinical trials have explored HSP90 inhibitors for use in inflammatory and autoimmune diseases [19–21].
Discovery of N-aryl sulphonamide-quinazoline derivatives as anti-gastric cancer agents in vitro and in vivo via activating the Hippo signalling pathway
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2021
Jin-Bo Niu, Chun-Hua Quan, Yuan Liu, Guang-Xi Yu, Jia-Jia Yang, Yin-Ru Li, Yan-Bing Zhang, Ying-Qiu Qi, Jian Song, Cheng-Yun Jin, Sai-Yang Zhang
Hippo signalling pathway is a highly conserved signalling cascade that initially was identified in Drosophila1–3. It was found to be a crucial regulator on cell survival, proliferation, and differentiation mammals in the last several years4–9. In mammal cells, the Hippo pathway contains protein kinases of Salvador homolog (SAV) 1, Mammalian STE20-like protein kinase (MST) 1/2, Large tumour suppressor (LATS) 1/2, Mps one binder kinase activator-like (MOB) 1. These proteins regulate downstream effectors of Yes-associated protein (YAP), transcriptional co-activator with PDZ-binding motif (TAZ), and transcriptional enhanced associate domain (TEAD)1–4. In the signalling cascade, phosphorylated MST1/2 could phosphorylate and activate LATS1/2. Phosphorylated LATS1/2 would phosphorylate YAP in the cytoplasm. SAV1 and MOB1, two scaffold proteins, could be activated by MST1/2. The phosphorylated YAP would be degraded via the ubiquitin-proteasome system10. Activated (non-phosphorylated) YAP would be translocated from the cytoplasm to the cell nuclear11,12. In cell nuclear, YAP together with TEADs regulates its target oncogene proteins like c-Myc and Bcl-2. YAP is over-activated in many cancers5,13–15 like breast cancer16, lung cancer17, colorectal cancer18, gastric cancer19, and prostate cancer20, and its negatively regulated oncogenic target gene expression is higher than that of normal cells21. Therefore Hippo/YAP is now believed as a promising target for cancer therapy, because of its close relation with tumour development22–24. However, there are few reported molecule modulators of the Hippo pathway and most of them did not act potent anticancer activity25–30.
A systematic review of targeted agents for non-small cell lung cancer
Published in Acta Oncologica, 2018
Hannah H. Vestergaard, Marcus R. Christensen, Ulrik N. Lassen
A PubMed database systematic literature search was conducted using the following search words: ((‘Carcinoma, Non-Small-Cell Lung’(Mesh)) AND ((((((((((‘Precision Medicine’(Mesh)) OR ‘targeted medicine’) OR ‘person specific medicine’) OR ‘novel therapy’) OR ‘Genes, erbB-1’(Mesh)) OR ‘Genes, erbB-2’(Mesh)) OR ‘CMET’) OR ‘Proto-Oncogene Proteins p21(ras)’(Mesh)) OR ‘Proto-Oncogene Proteins B-raf’(Mesh)) OR ‘ALK’) AND (((‘Disease-Free Survival’(Mesh)) OR ‘response rate’) OR (((‘Survival Rate’(Mesh)) OR ‘overall survival’))). This provided 265 hits.