Onpa monta vastausta,yli 6100.
Toinen asia: Löytyykö uusia syövänvastaisia strategioita tai jopa täsmälääkkeitä tämän assosiaatio-alueen järjestelmistä?
Vuodelta 2016 Haifasta tutkimustuloksia Semaforiinien osuudesta syövässä
The role of the semaphorins in cancerGera Neufeld et al. Pages 652-674
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Received 03 Jan 2016, Accepted 30 May 2016, Published online: 17 Aug 2016 https://doi.org/10.1080%2F19336918.2016.1197478
Conclusions. Initially it was thought that the semaphorins would function primarily as inhibitors of tumor progression and tumor angiogenesis. This turned out not to be the case and by now several semaphorins have been found to promote tumor progression and to enhance angiogenesis. Furthermore, several semaphorins were reported both to induce and to inhibit tumor progression. These different activities seem context dependent and there is evidence suggesting that interactions between semaphorin receptors and apparently unrelated receptors such as various tyrosine-kinase receptors as well as post translational modifications of the semaphorins and their receptors can profoundly affect their biological activities as exemplified in the case of sema3E.71,174,186,189 These interactions and modifications can in turn profoundly affect the course of diseases such as cancer, and a better understanding of these interactions and post translational modifications is required if one considers the development of anti-tumorigenic and anti-angiogenic therapeutic agents that target or utilize semaphorin signal transduction. Thus, research aimed at a better understanding of the processing of semaphorins and their receptors and better characterization of the cross-talk between semaphorins and their receptors and other signal transduction systems is likely to be a focus of research for some time to come. In addition to cancer, it seems that semaphorins play major regulatory roles in the development and maintenance of the vascular and neuronal networks of organs such as the retina and the kidney, and it is likely that the study of the role of the semaphorins in the development of vascular diseases such as complications of diabetes such as diabetic retinopathy or diabetic nephropathy will also become a focus of intensive research in the near future.
- Otan tämän artikkelin viitteistä sellaisen, jossa näkyy suomalainen tutkija vuonna 2003 selvittämässä Sema 3A kiderakennetta ja interaktiokohtia . Siinä vaiheessa havaittiin beta-propellirakenne.
- Antipenko A, Himanen JP, van Leyen K, Nardi-Dei V, Lesniak J, Barton WA, Rajashankar KR, Lu M, Hoemme C, Puschel AW, and others. Structure of the semaphorin-3A receptor binding module. Neuron 2003; 39:589-98; PMID:12925274; The semaphorins are a large group of extracellular proteins involved in a variety of processes during development, including neuronal migration and axon guidance. Their distinctive feature is a conserved 500 amino acid semaphorin domain, a ligand-receptor interaction module also present in plexins and scatter-factor receptors. We report the crystal structure of a secreted 65 kDa form of Semaphorin-3A (Sema3A), containing the full semaphorin domain. Unexpectedly, the semaphorin fold is a variation of the beta propeller topology. Analysis of the Sema3A structure and structure-based mutagenesis data identify the neuropilin binding site and suggest a potential plexin interaction site. Based on the structure, we present a model for the initiation of semaphorin signaling and discuss potential similarities with the signaling mechanisms of other beta propeller cell surface receptors, such as integrins and the LDL receptor.
- Vuodelta 2021 tutkimus semaforiinien ja plexiini- neuropiliini-reseptorin komplekseista elävän solun solukalvosoissa:
- J Biol Chem. 2021 Aug; 297(2): 100965. Published online 2021 Jul 13. doi: 10.1016/j.jbc.2021.100965
- PMCID: PMC8350011 PMID: 34270956 Interactions between semaphorins and plexin–neuropilin receptor complexes in the membranes of live cells Shaun M. Christie,
- Overall, the work here has investigated only a subset of the potential interactions within the plexin–neuropilin–semaphorin protein family. More receptors and ligand combinations will need to be analyzed to establish a more expansive and holistic understanding of how membrane protein–protein interactions regulate plexin–semaphorin signaling. Because of the large number of ligands and receptors (seven class 3 semaphorins, nine plexin receptors, and two neuropilins), this is a time- and resource-intensive undertaking. The work we presented here lays the groundwork for such a comprehensive study. PIE-FCCS is an ideal method for quantifying these interactions in a live cell environment. Combined with cell signaling and high-resolution structure studies, it will be possible to resolve the function role of receptor homodimerization and heterodimerization in this important signaling axis. This work will also reveal how dysregulated signaling by plexins and neuropilins influence disease states, which will enable new approaches for designing therapeutic strategies.
https://www.tandfonline.com/doi/full/10.1080/19336918.2016.1197478
Tässä linkissä on selkeitä kaavakuvia kyseessä olevista moduleista.
tässä yhteydessä en vielä löytänyt näitten signallointien ja Ki-67 indeksin suoranaistq yhteyttä. ...
- Haku assosiaatiosta Ki-67 AND neuropilins: https://pubmed.ncbi.nlm.nih.gov/35473507/
The expression levels of NRP-2 mRNA in the cells were detected by real-time fluorescence quantitative PCR. The expressions of proliferation-associated protein Ki-67 in the cells were detected by immunochemical staining ... Effects of silencing neuropilin-2 on proliferation, migration, and invasion of colorectal cancer HT-29
- Claudin-low breast cancer:
https://breast-cancer-research.biomedcentral.com/articles/10.1186/s13058-022-01501-7
Claudins: The Newly Emerging Targets in Breast Cancer
Finally, we show that NRP1 acts as a central hub for the aberrant activation of the RAS-MAPK pathway via EGFR and PDGFR activation to drive aggressive tumor progression, a hallmark of all claudin-low subgroups. These data identify NRP1 as a key driver of the claudin-low phenotype and support further testing of NRP1 inhibitors for improved control of claudin-low tumor progression.
- Haku: claudin low tumors, Ki-67 index?
For claudin 3, 4, 7 and E-cadherin a score of ≤4 was considered 'low' expression. For Ki67 a minimum of 100 tumor nuclei were counted per core and the tumor was considered Ki67 'low' if the percentage of positively stained nuclei was <14% and Ki67 'high' is the percentage of positively stained nuclei was ≥14% [12, 24].
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