Human cytotoxic T lymphocyte (CTL) granules contain an electron-dense core and small membrane vesicles. By immuno-electron microscopy, molecules relevant to CTL-target cell (TC) interactions have been identified on the membranes of the dense core and small vesicles within the granule. Moreover, perforin, the component implicated in the lethal hit, and serine esterases are localized within these granule substructures. In this article Peter Peters and colleagues argue that these observations necessitate a revision of the current model for lethal hit delivery. They suggest that the cytotoxic mediators exocytosed into the cleft between CTL and TC are not in soluble form, but rather are membrane-enveloped. The presence of the CD3-T-cell receptor (TCR) complex, CD8 and possibly other relevant molecules on these membranes may ensure unidirectional delivery of the lethal compounds to the TC.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/0167-5699(90)90008-w | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Discovery of Novel Spirocyclic MAT2A Inhibitors Demonstrating High In Vivo Efficacy in MTAP-Null Xenograft Models.
J Med Chem
January 2025
Medicinal Chemistry Department, Shanghai Haiyan Pharmaceutical Technology Co., Ltd., Pudong New Area, Shanghai 201203, China.
Synthetic lethality offers a robust strategy for discovering the next generation of precision medicine therapies tailored for molecularly defined patient populations. MAT2A inhibition is synthetically lethal in several cancers that exhibit a homozygous deletion of -methyl-5'-thioadenosine phosphorylase (MTAP). Herein, we report the identification of novel MAT2A inhibitors featuring a spiral ring to circumvent the C-N atropisomeric chirality utilizing structure-based drug design.
View Article and Find Full Text PDFOncogenic RTKs sensitize cancer cells to ferroptosis via c-Myc mediated upregulation of ACSL4.
Cell Death Dis
November 2024
The HIT Center for Life Sciences, School of Life Science and Technology, Harbin Institute of Technology, Harbin, China.
Alteration or abnormal activation of RTKs have been recurrently observed and recognized as an important driving factor in the progression of many human cancers. Ferroptosis, an iron-dependent form of regulated necrosis triggered by the accumulation of lethal lipid peroxides on cell membranes, has been implicated in various tumor types. Here we reported that oncogenic RTKs/RAS/RAF/c-Myc axis promotes cancer cells to ferroptosis.
View Article and Find Full Text PDFDouble Heterozygous Pathogenic Variants in and in Boy with Undifferentiated Embryonal Sarcoma of the Liver.
Int J Mol Sci
October 2024
Human Genetics, Faculty of Medicine, University of Augsburg, 86156 Augsburg, Germany.
Undifferentiated embryonal sarcoma of the liver is a rare mesenchymal malignancy that predominantly occurs in children. The relationship between this tumor entity and germline pathogenic variants (PVs) remains undefined. Here, we present the clinical case of a male patient diagnosed with undifferentiated embryonal sarcoma of the liver.
View Article and Find Full Text PDFSilencing of maternally expressed RNAs in Dlk1-Dio3 domain causes fatal vascular injury in the fetal liver.
Cell Mol Life Sci
October 2024
School of Life Science and Technology, State Key Laboratory of Urban Water Resource and Environment, Harbin Institute of Technology, Harbin, 150001, China.
Article Synopsis
- The Dlk1-Dio3 domain in mammals contains important genetic elements, including lncRNAs, mRNAs, and a large miRNA cluster, and its deletion affects embryonic development, leading to death.
- Researchers created a mouse model to investigate how silencing maternally expressed RNAs in this domain results in apoptosis, specifically affecting the liver, ultimately causing fetal hemorrhage.
- The study reveals that the silencing of these RNAs activates paternally expressed genes, and this process—rather than the differential methylation regions—leads to embryonic death due to liver damage.
Isoxazole compounds: Unveiling the synthetic strategy, in-silico SAR & toxicity studies and future perspective as PARP inhibitor in cancer therapy.
Eur J Med Chem
December 2024
Department of Pharmacy, Guru Ghasidas Vishwavidyalaya (A Central University), Bilaspur, C.G., 495009, India. Electronic address:
Latest developments in cancer treatment have shed a light on the crucial role of PARP inhibitors that enhance the treatment effectiveness by modifying abnormal repair pathways. PARP inhibitors, such as Olaparib, Rucaparib, Niraparib, and Talazoparib have been approved in a number of cancers including BRCA 1/BRCA2 associated malignancies although there are many difficulties as therapeutical resistance. Besides the conventional synthetic drugs, natural compounds such as flavones and flavonoids have been found to be PARP inhibitors but only in preclinical studies.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!