29 research outputs found
Libri manuseripti Graeci in Bibliotheois Budapestinensibus asservati - Descripsit Maria Kubinyi, Budapestini, MCMLVI. Akadémiai Kiadó
Renaissance tanulmányok : írták: Sallay Géza, Faragó Péterné, Rózsa Zoltán, Herczeg Gyula, Gáldi László, Nádor György, Kardos Tibor. — Szerkesztette: Kardos Tibor, Budapest, 1957. 542 1.
Mezey László: "Irodalmi anyanyelvűségünk kezdetei és a középkori laikus mozgalmak" című kandidátusi disszertációjának vitája
Opponensi vélemények és Mezey László válasz
Prognosis in human glioblastoma based on expression of ligand growth hormone-releasing hormone, pituitary-type growth hormone-releasing hormone receptor, its splicing variant receptors, EGF receptor and PTEN genes
Purpose G lioblastoma (GB) is the most frequent brain
tumor. Despite recent improvement in therapeutic strategies,
the prognosis of GB remains poor. Growth hormone-releasing
hormone (GHRH) may act as a growth factor; antagonists
of GHRH have been successfully applied for experimental
treatment of different types of tumors. The expression profile
of GHRH receptor, its main splice variant SV1 and GHRH
have not been investigated in human GB tissue samples.
Methods We examined the expression of GHRH, fulllength
pituitary-type GHRH receptor (pGHRHR), its functional
splice variant SV1 and non-functional SV2 by RTPCR
in 23 human GB specimens. Epidermal growth factor
receptor (EGFR) and phosphatase and tensin homolog gene
(PTEN) expression levels were also evaluated by quantitative
RT-PCR. Correlations between clinico-pathological
parameters and gene expressions were analyzed.
Results E xpression of GHRH was found to be positive
in 61.9 % of samples. pGHRH receptor was not expressed
in our sample set, while SV1 could be detected in 17.4 %
and SV2 in 8.6 % of the GB tissues. In 65.2 and 78.3 %
of samples, significant EGFR over-expression or PTEN
under-representation could be detected, respectively. In
47.8 % of cases, EGFR up-regulation and PTEN down-regulation
occurred together. Survival was significantly poorer
in tumors lacking GHRH expression. This worse prognosis
in GHRH negative group remained significant even if SV1
was also expressed.
Conclusion Our study shows that GHRH and SV1 genes
expressed in human GB samples and their expression patterns
are associated with poorer prognosis
Human keratinocytes are vanilloid resistant
BACKGROUND: Use of capsaicin or resiniferatoxin (RTX) as analgesics is an attractive therapeutic option. RTX opens the cation channel inflammatory pain/vanilloid receptor type 1 (TRPV1) permanently and selectively removes nociceptive neurons by Ca(2+)-cytotoxicity. Paradoxically, not only nociceptors, but non-neuronal cells, including keratinocytes express full length TRPV1 mRNA, while patient dogs and experimental animals that underwent topical treatment or anatomically targeted molecular surgery have shown neither obvious behavioral, nor pathological side effects. METHODS: To address this paradox, we assessed the vanilloid sensitivity of the HaCaT human keratinocyte cell line and primary keratinocytes from skin biopsies. RESULTS: Although both cell types express TRPV1 mRNA, neither responded to vanilloids with Ca(2+)-cytotoxicity. Only ectopic overproduction of TRPV1 rendered HaCaT cells sensitive to low doses (1-50 nM) of vanilloids. The TRPV1-mediated and non-receptor specific Ca(2+)-cytotoxicity ([RTX]>15 microM) could clearly be distinguished, thus keratinocytes were indeed resistant to vanilloid-induced, TRPV1-mediated Ca(2+)-entry. Having a wider therapeutic window than capsaicin, RTX was effective in subnanomolar range, but even micromolar concentrations could not kill human keratinocytes. Keratinocytes showed orders of magnitudes lower TRPV1 mRNA level than sensory ganglions, the bona fide therapeutic targets in human pain management. In addition to TRPV1, TRPV1b, a dominant negative splice variant was also noted in keratinocytes. CONCLUSION: TRPV1B expression, together with low TRPV1 expression, may explain the vanilloid paradox: even genuinely TRPV1 mRNA positive cells can be spared with therapeutic (up to micromolar) doses of RTX. This additional safety information might be useful for planning future human clinical trials