3 research outputs found
Minimal and inducible regulation of tissue factor pathway inhibitor-2 in human gliomas
Tissue factor pathway inhibitor-2 (TFPI-2), a serine protease inhibitor
abundant in the extra cellular matrix, is highly expressed in
non-invasive cells but undetectable levels in highly invasive human
glioma cells. The mechanisms responsible for its transcriptional
regulation are not well elucidated. In this study, we made several
deletion constructs from a 3.6 kb genomic fragment from Hs683 cells
containing the 5’-flanking region of the TFPI-2 gene, transiently
transfected with these constructs into non-invasive (Hs683) and highly
invasive (SNB19) human glioma cells, and assessed their expression by
using a luciferase reporter gene. Three constructs showed high promoter
activity (pTF5, -670 to +1; pTF6, -312 to +1; pTF2, -1511 to +1).
Another construct, pTF8 (-81 to +1), showed no activity. PTF9, a variant
of pTF5 in which a further 231 bp fragment (-312 to -81) was deleted,
from the [-670 to +1] pTF5 region, also showed no promoter activity.
Hence, (-312 to -81) this region is essential for the transcription of
TFPI-2 in glioma cells. Sequencing of this promoter region revealed that
it has a high G+C content, contains potential SP1 and AP1 binding
motifs, and lacks canonical TATA and CAAT boxes immediately upstream of
the major transcriptional initiation site, although CAAT boxes were
found about -3000 bp upstream of the transcription start site. We also
found a strong repressor in the region between -927 to -1181, upstream
of the major transcriptional initiation site, followed by positive
elements or enhancers between -1511 to -1181. These positive elements
masked the silencer effect. Finally TFPI-2 was induced in Hs683 cells
transfected with the pTF6 construct (-312 to + 1) and stimulated with
phorbol-12-myristate-13-acetate (PMA). We conclude that the -312 to +1
region is critical for the minimal and inducible regulation of TFPI-2 in
non-invasive (Hs683) and highly invasive (SNB19) human glioma cell
lines
RETRACTED: Down-regulation of integrin alpha(v)beta(3) expression and integrin-mediated signaling in glioma cells by adenovirus-mediated transfer of antisense urokinase-type plasminogen activator receptor (uPAR) and sense p16 genes (Retracted article. See vol. 295, pg. 13134, 2020)
Interaction between the extracellular matrix and integrin receptors on
cell surfaces leads not only to cell adhesion but also to intracellular
signaling events that affect cell migration, proliferation, and
survival. The vitronectin receptor alpha (v)beta (3) integrin is of key
importance in glioma cell biology. The expression of urokinase-type
plasminogen activator receptor (uPAR) was recently shown to co-regulate
with the expression of alpha (v)beta (3), integrin. Moreover,
restoration of the p16 protein in glioma cells inhibits the alpha
(v)beta (3) integrin-mediated spreading of those cells on vitronectin.
Thus we hypothesized that adenovirus-mediated down-regulation of uPAR
and overexpression of p16 might down-regulate the expression of alpha
(v)beta (3) integrin and the integrin-mediated signaling in glioma
cells, thereby defeating the malignant phe. notype. In this study, we
used replication-deficient adenovirus vectors that contain either a uPAR
antisense expression cassette (Ad-uPAR) or wild-type p16 cDNA (Ad-p16)
and a bicistronic adenovirus construct in which both the uPAR antisense
and p16 sense expression cassettes (Ad-uPAR/p16) are inserted in the
El-deleted region of the vector. Infecting the malignant glioma cell
line SNB19 with Ad-uPAR, Ad-p16, or Ad-uPAR/p16 in the presence of
vitronectin resulted in decreased alpha (v)beta (3) integrin expression
and integrin-mediated biological effects, including adhesion, migration,
proliferation, and survival Our results support the therapeutic
potential of simultaneously targeting uPAR and p16 in the treatment of
gliomas
Spontaneous Resolution Of Syringomyelia Without Chiari Malformation - Case Report
A 30-year-old woman presented with a cervical syrinx manifesting as hemihypesthesia. Neuroimaging found no evidence of Chiari malformation or tight cisterna magna. Serial magnetic resonance imaging studies over a 6-year period demonstrated spontaneous and complete resolution of the syrinx accompanied by an asymptomatic clinical course. The natural history of syringomyelia is highly unpredictable. The outcome of surgical treatment for patients with syringomyelia is not always satisfactory, so the indications for surgery are controversial. Spontaneous resolution of syringomyelia unrelated with foramen magnum lesion has various causes. Close follow up of the patient is necessary to monitor for recurrence.WoSScopu