PubMed · 8668708
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S B Cutler. 1996. A survivor's tale.. https://pubmed.ncbi.nlm.nih.gov/8668708/
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The chemokine RANTES is an important mediator of inflammatory processes. In this report, we describe the DNA sequence and transcription factor requirements for interleukin-1beta (IL-1beta) induction of the RANTES promoter in the human astrocytoma line CH235. RANTES promoter sequences between -278 and +55 are sufficient for IL-1beta-inducibility. In vitro DNA binding assays demonstrate constitutive binding of Sp1, HMG, Ets domain, and bZIP family members to their cognate sites in the RANTES promoter, whereas NF-kappaB and IRF-1 bind in an IL-1beta-inducible manner. IL-1beta-inducibility of the RANTES promoter requires both constitutive and inducible transcription factors. The formation of a higher order nucleoprotein complex, or 'enhanceosome', may be critical for IL-1beta induction of the RANTES promoter.
UNLABELLED: Many of the problems associated with the current grading approaches for fibrillary astrocytomas center around the lack of consistency in grading. This study compares the diagnoses of five neuropathologists with five experienced surgical pathologists with regard to assigning astrocytoma grade. Thirty neoplastic and non-neoplastic lesions were sent to each of five neuropathologists and five surgical pathologists for placement into one of three grades as outlined by modified Ringertz schema. Grading criteria (Burger et al., 1985. Cancer 56:1106-1111) were distributed to all participants, who have been practicing for at least 5 years. An additional category for non-neoplastic or normal tissue was also provided. The diagnoses, based on the majority opinion of the neuropathologist group, included six low grade astrocytomas, 11 anaplastic astrocytomas, seven glioblastoma multiforme, and six normal/reactive lesions. Agreement by all neuropathologists was reached in 12 cases (40%). A discrepant diagnosis was obtained in one of five neuropathologists in 14 additional cases (46.7%). In the remaining four cases, two neuropathologists deviated from the majority opinion; in each of these cases, the diagnostic problem involved differentiating tumor from reactive gliosis. All five surgical pathologists agreed in six cases (20%). One discrepant diagnosis among the surgical pathologist group was seen in seven cases (23.3%). In the remaining 17 cases, two or more discrepant diagnoses were obtained (56.7%); discrepancies in these cases included differences in assignment of tumor grade and in distinguishing low grade astrocytoma from gliosis. IN CONCLUSION: (1) it is likely that experience with grading accounts for the better level of agreement among the neuropathologist group (kappa statistic 0.63) versus the surgical pathologist group (kappa statistic 0.36); (2) in most cases, the neuropathologists all agreed or had one discrepant diagnosis (86.7%) versus the surgical pathologist group (43.3%); (3) the discrepancies in diagnosis among both groups is likely related, in good part, to the limitations of the grading schema in fully enumerating the spectrum of such grading parameters as cytologic atypia and vascular proliferation.
Elevation of the cyclin-dependent kinase (cdk) inhibitor, p27(kip1) is necessary for Interleukin (IL)-4-mediated growth arrest of human low grade astrocytoma (RTLGA) cells and occurs at 24 h of treatment. Pathways involved in IL4 alteration of p27(kip1) are unknown, however. Here we investigated whether other cdk inhibitors contributed to the actions of IL-4 on RTLGA cells. By 12 h of IL-4 treatment, both cdk4 and cdk2 kinase activities against the retinoblastoma protein (pRb) were reduced and nuclear entry of pRb was prohibited. Twelve-hour cdk complexes contained elevated p21(waf1/cip1) but not p27(kip1), p15(ink4B) or p16(ink4A). IL-4 increased p21(waf1/cip1) but not p27(kip1) mRNA levels, and stimulated luciferase activity of a p21(waf1/cip1) promoter-luciferase reporter. In p53-mutant WITG3 cells, IL-4 did not alter p21(waf1/cip1) mRNA and promoter-luciferase activity or p27(kipl) protein, suggesting a need for functional p53. STAT6 phosphorylation by IL-4, however, occurred in both p53-mutant WITG3 and p53-functional RTLGA cells. Pre-treatment of RTLGA with anti-sense but not missense p21(waf1/cip1) oligonucleotide prior to IL-4: (a) restored cdk activities; (b) reduced cdk4-associated p21(waf1/cip1) levels; (c) prevented p27(kipl) elevation; and (d) reversed growth arrest. These results are the first to suggest that p21(waf1/cip1) is essential for IL-4-mediated elevation of p27(kip) and growth arrest of astrocytoma cells.