TNF-related apoptosis-inducing ligand (TRAIL) selectively induces programmed cell death (apoptosis) in various cancer cells but not in normal cells. TRAIL is known to bind to 4 different receptors, 2 proapoptotic (DR4 andDR5Several members of the tumor necrosis factor receptor superfamily, which includes tumor necrosis factor receptor 1, Fas (Apo-1/CD95), and the decoy receptors for TRAIL (Apo-2L), regulate programmed cell death (apoptosis). Upon engagement by their respective ligands, tumor necrosis factor receptor 1 and Fas recruit adaptor molecules and activate a cascade of cysteine proteases (caspases), the proteolytic activity of which results in apoptosis. The TRAIL-activated DR4 (also TNFRSF10A, Apo-2, TRAIL-R1) 1,2 and DR5 (also TNFRSF10B, KILLER/DR5, TRICK2, TRAIL-R3) receptors 2-4 have also been shown to initiate a caspase-mediated apoptotic pathway. 4 Death inducing DR4 and DR5 and the decoy receptors DcR1 (also TNFRSF10C, TRID, TRAIL-R3) and DcR2 (also TNFRSF10D, TRUNDD, TRAIL-R4) are structurally related, especially in their extracellular domains and are all located at 8p 21-22. 5,6 Decoy receptor DcR1 completely lacks the intra-cellular death domain and DcR2 contains a truncated, nonfunctional death domain and appear unable to induce apoptosis. The extracellular domains of DcR1 or DcR2 compete with those of DR4 or DR5 for TRAIL binding. Thus, based on the current knowledge, DcR1 or DcR2 are believed to inhibit apoptosis induction mediated through DR4 and DR5. 5 Inactivation of genes may occur via point mutations, allelic loss (LOH), homozygous deletions or by aberrant methylation. 7-9 Aberrant methylation of 5Ј gene promoter regions associated with gene silencing is an epigenetic phenomenon involving many genes observed in almost all cancer types, including breast cancers, lung cancers and mesotheliomas. 9 -18 We have demonstrated loss of expression (at RNA and protein level) of DR4 and DR5 in lung cancer cell lines, although the mechanism was not via methylation. 19 Recently, 20 it was reported that DcR1 and DcR2 expression are frequently silenced by aberrant methylation of 5Ј regions of these genes in pediatric tumor cell lines and neuroblastomas. In our study, we examined the methylation and expression status of DcR1, DcR2, DR4 and DR5 in breast and lung cancers and malignant mesothelioma (MM). We also examined the methylation status of TRAIL receptor genes in many other types of malignancies. We tried to correlate methylation status with clinical features of patients including survival and histological type in lung breast MM and prostate cancer. MATERIAL AND METHODS Cell linesCell lines were initiated by AFG (breast, lung, some MMs) or HIP (most MMs). [21][22][23] Twenty-seven lung cancer cell lines and 23 breast cancer cell lines and were grown in RPMI-1640 medium (Life Technologies Inc., Rockville, MD) supplemented with 5% FBS and incubated in 5% CO 2 at 37°C. Four non-malignant mesothelial primary cell cultures (HCC3466, HCC3468, HCC3469,
Traumatic microbleeds are a common neuroimaging finding in traumatic brain injury, yet their clinical significance remains unclear. Griffin et al. report that traumatic microbleeds predict disability, and use MRI-guided histopathology to elucidate the underlying pathophysiology. They conclude that traumatic microbleeds may be a form of traumatic vascular injury.
Background and Purpose-Detection of an intracardiac shunt is frequently sought during the evaluation of patients with cryptogenic ischemic stroke and agitated saline intravenous injection, or "bubble study" (BS), is performed in most cases. We present the first attempt to identify the clinical features in patients who had cerebral ischemic events with BS. Methods-Using a list serve established by the American Academy of Neurology, a member posted a question regarding the safety of BS in patients with patent foramen ovale. A standardized questionnaire was used to gather data about patients with cerebral ischemic events, details of each case were reviewed, and the findings pooled. Results-Five patients with ischemic complications of BS (all female, aged 42 to 90 years) were identified from 4 institutions, 3 ischemic strokes and 2 transient ischemic attacks. Events occurred either during or within 5 minutes of BS. Early brain MRIs confirmed acute infarction in 3, including one who had transient symptoms. MRI infarct volumes were small, and deficits were mild in those who developed stroke. Diagnostic evaluation revealed a patent foramen ovale alone in one case, a pulmonary arteriovenous malformation in one case, and a patent foramen ovale and/or pulmonary shunt in 3 cases. Conclusions-Ischemic cerebrovascular complications can occur in patients who undergo BS and are associated with the presence of cardiac or pulmonary shunts. The true incidence and degree of disability remains unknown, and further study is indicated to assess the impact of technical differences in BS methodology.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.