Ich habe eine Veröffentlichung gefungen, in welcher beschrieben wird, dass das häufigste Therapeutikum zur Behandlung Platinbasierte Medikamente sein sollen. Leider sprechen jedoch nur etwa 50 % der Patienten auf diese Medikamente
an. Nun beschreibt die genannte Veröffentlichung, das man mit Hilfe
eines modernen Verfahrens durch die Untersuchung von Krebszellen dieser
Patienten aushalb des Körpers (also in vitro) vor der Behandlung feststellen kann, ob die verwendeten Therapeutika die gewünschte Wirkung zeigen oder nicht.
Das hat den Vorteil, dass jene Patenten, bei denen Platin-basierte Medikamente nicht wirken, diese auch nicht den Nebenwirkungen eines bei ihnen unwirksamen Medikamentes ausgesetzt sind.
Guckst Du hier ( leider nur in Englisch):
Increased expression of transcription factor TFAP2a correlates with chemosensitivity in advanced bladder cancer
Iver Nordentoft1*, Lars Dyrskjøt1, Julie S Bødker1, Peter J Wild2, Arndt Hartmann3, Simone Bertz3, Jan Lehmann4,
Torben F Ørntoft1 and Karin Birkenkamp-Demtroder1
Nordentoft et al. BMC Cancer 2011, 11:135
BMC Cancer | Full text | Increased expression of Transcription Factor TFAP2 alpha
correlates with chemosensitivity in advanced bladder cancer
Abstract
Background: The standard treatment for patients with advanced transitional cell carcinoma of the bladder is platin
based chemotherapy. Only approximately 50% of the patients respond to chemotherapy. Therefore, molecular
predictive markers for identification of chemotherapy sensitive subgroups of patients are highly needed. We
selected the transcription factor TFAP2a from a previously identified gene expression signature for chemotherapy
response.
Methods: TFAP2a expression and localization was assessed by immunohistochemistry using a tissue microarray
(TMA) containing 282 bladder cancer tumors from patients with locally advanced (pT2-T4b and N1-3) or metastatic
(M1) disease. All patients had received cisplatin containing chemotherapy. Furthermore, QPCR analysis of three
TFAP2a isoforms was performed on tumor specimens of advanced muscle invasive bladder cancers (T2-4). Using
the bladder cell lines T24 and SW780 the relation of TFAP2a and cisplatin and gemcitabine sensitivity as well as
cell proliferation was examined using siRNA directed TFAP2a knockdown.
Results: TFAP2a protein expression was analyzed on a TMA with cores from 282 advanced bladder cancer tumors
from patients treated with cisplatin based combinational chemotherapy. TFAP2a was identified as a strong
independent predictive marker for a good response and survival after cisplatin-containing chemotherapy in
patients with advanced bladder cancer. Strong TFAP2a nuclear and cytoplasmic staining predicted good response
to chemotherapy in patients with lymph node metastasis, whereas weak TFAP2a nuclear staining predicted good
response in patients without lymph node metastasis. In vitro studies showed that siRNA mediated knockdown of
TFAP2a increased the proliferation of SW780 cells and rendered the cells less sensitive to cisplatin and
gemcitabine. In contrast to that T24 bladder cells with mutated p53 showed to be more drug sensitive upon
TFAP2a depletion.
Conclusions: High levels of nuclear and cytoplasmic TFAP2a protein were a predictor of increased overall survival
and progression free survival in patients with advanced bladder cancer treated with cisplatin based chemotherapy.
TFAP2a knockdown increased the proliferation of the SW780 bladder cells and reduced cisplatin and gemcitabine
induced cell death. The inverse effect was observed in the TP53 mutated T24 cell line where TFAP2a silencing
augmented cisplatin and gemcitabine sensitivity and did not stimulate proliferation.
Anmerkung: Ich habe diesen kopierten Artikel aus dem Blog von Thomas G hierher verschoben weil er kein Blog Thema ist.
Der Blog wurde gelöscht. (Rainer 25.05.2016)