aHIF but not HIF-1α transcript is a poor prognostic marker in human breast cancer

BACKGROUND: Hypoxia-inducible factor-1α (HIF-1α) is part of a transcriptional factor that regulates genes involved in metabolic and vascular adaptation of tumours to oxygen restriction. A splicing variant lacking exon 14 (sHIF-1α) encodes a truncated protein that competes with the normal HIF-1α protein, decreasing its activity. A natural antisense transcript (aHIF) complementary to the 3'-untranslated region of HIF-1α mRNA was described recently. METHODS: With a semiquantitative multiplex reverse transcriptase–PCR (RT–PCR) assay, we assessed transcript concentrations of HIF-1α, sHIF-1α and aHIF in 110 patients with invasive breast carcinoma. RESULTS: We found a strong positive association between HIF-1α and sHIF-1α, sHIF-1α and aHIF, and an inverse correlation between HIF-1α /sHIF-1α and aHIF. aHIF transcript expression was associated with poor disease-free survival in univariate (P = 0.0038) and multivariate (P = 0.0016) analyses in this series of high-risk primary breast carcinomas. CONCLUSION: In our series of breast cancer patients, aHIF, and not HIF-1α transcript, is a marker of poor prognosis

Adaptation moléculaire à l'hypoxie via le facteur de transcription HIF-1 (aspects physiologiques et pathologiques)

CLERMONT FD-BCIU-Santé (631132104) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF

Etude de deux facteurs de transcription impliqués dans le développement des mélanomes et la formation de métastases (N Oct-3 et HIF-2alpha)

TOULOUSE3-BU Sciences (315552104) / SudocSudocFranceF

Etude du mécanisme de l'action antinociceptive du paracétamol (interaction avec le système sérotoninergique)

CLERMONT FD-BCIU-Santé (631132104) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF

Expression dans le leucocyte et le muscle de la sous-unité alpha d'HIF-1 et de son antisens naturel chez des athlètes de haut niveau entraînés en hypoxie

CLERMONT FD-BCIU-Santé (631132104) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF

Expression dans le leucocyte et le muscle de la sous-unité alpha d'HIF-1 et de son antisens naturel chez des athlètes de haut niveau entraînés en hypoxie

CLERMONT FD-BCIU-Santé (631132104) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF

Régulation de l'expression génique dans les mélanomes (implication des facteurs de transcription N Oct-3 et HIF)

TOULOUSE3-BU Sciences (315552104) / SudocSudocFranceF

Orally administered paracetamol does not act locally in the rat formalin test: evidence for a supraspinal, serotonin-dependent antinociceptive mechanism.

The mechanism of action of paracetamol (acetaminophen) remains elusive because it is still under discussion as to whether it acts locally and/or centrally. The primary aim of this study was to clarify its site(s) of action (central and/or local) using the rat formalin test.info:eu-repo/semantics/publishe

Spinal 5-HT1A receptors differentially influence nociceptive processing according to the nature of the noxious stimulus in rats: effect of WAY-100635 on the antinociceptive activities of paracetamol, venlafaxine and 5-HT.

The regulation of nociceptive processing by 5-HT at the spinal level is intricate since the neurotransmitter has been implicated in both pro and antinociception. The aim of our study was to investigate, according to the nature of the noxious stimulus, how the blockade of spinal 5-HT(1A) receptors could influence the antinociceptive actions of exogenous 5-HT as well as two analgesics involving endogenous 5-HT, paracetamol and venlafaxine. Rats were submitted either to the formalin test (tonic pain) or the paw pressure test (acute pain). WAY-100635 (40 microg/rat, i.t.), a selective 5-HT(1A) receptor antagonist, had no intrinsic action in either test. However, in the formalin test, it blocked the antinociceptive action of 5-HT (50 microg/rat, i.t.) and paracetamol (300 mg/kg, i.v.) in both phases of biting/licking behaviour and that of venlafaxine (2.5 mg/kg, s.c.) in the late phase only. In the paw pressure test, the combination of sub-effective doses of 5-HT (0.01 microg/rat, i.t.), paracetamol (50 mg/kg, i.v.) or venlafaxine (20 mg/kg, s.c.) with WAY-100635 led to a significant antinociceptive effect, which seems to depend on the reinforcement of the activity of inhibitory GABAergic interneurones. In conclusion, both direct stimulation of the spinal 5-HT(1A) receptors by 5-HT, and indirect stimulation using paracetamol or venlafaxine can differently influence pain transmission. We propose that the nature of the applied nociceptive stimulus would be responsible for the dual effect of the 5-HT(1A) receptors rather than the hyperalgesic state or the supraspinal integration of the pain message.info:eu-repo/semantics/publishe