Doreen Kunze

Enhanced Inhibition of Bladder Cancer Cell Growth by Simultaneous Knockdown of Antiapoptotic Bcl-xL and Survivin in Combination with Chemotherapy

The overexpression of antiapoptotic genes, such as Bcl-xL and survivin, contributes to the increased survival of tumor cells and to the development of treatment resistances. In the bladder cancer cell lines EJ28 and J82, the siRNA-mediated knockdown of survivin reduces cell proliferation and the inhibition of Bcl-xL sensitizes these cells towards subsequent chemotherapy with mitomycin C and cisplatin. Therefore, the aim of this study was to analyze if the simultaneous knockdown of Bcl-xL and survivin might represent a more powerful treatment option for bladder cancer than the single inhibition of one of these target genes. At 96 h after transfection, reduction in cell viability was stronger after simultaneous inhibition of Bcl-xL and survivin (decrease of 40%–48%) in comparison to the single target treatments (decrease of 29% at best). Furthermore, simultaneous knockdown of Bcl-xL and survivin considerably increased the efficacy of subsequent chemotherapy. For example, cellular viability of EJ28 cells decreased to 6% in consequence of Bcl-xL and survivin inhibition plus cisplatin treatment whereas single target siRNA plus chemotherapy treatments mediated reductions down to 15%–36% only. In conclusion, the combination of simultaneous siRNA-mediated knockdown of antiapoptotic Bcl-xL and survivin—a multitarget molecular-based therapy—and conventional chemotherapy shows great potential for improving bladder cancer treatment.

Carbon Nanotubes Filled with Carboplatin: Towards Carbon Nanotube-Supported Delivery of Chemotherapeutic Agents

Thanks to their capillary-like structure CNTs provide a well-characterized container material for hosting miscellaneous fillings. Here we present basic studies on the use of CNTs for drug delivery. By introducing carboplatin, an anticancer drug, into the CNTs via a wet chemical approach, drug-filled nanotubes have been produced. The maintenance of the structure of carboplatin was proven using electron energy loss spectroscopy and X-ray photoelectron spectroscopy. It was shown that the drug is released into cell culture medium leading to cell death. Cell viability assays performed with bladder cancer cells EJ28 demonstrated the cytotoxicity of CNTs filled with carboplatin. For comparison a reference of unfilled, open ended CNTs did not affect the cell viability. These results point out the general capabilities of CNTs as nanocarriers for drug delivery.

Antisense Oligonucleotides: Insights from Preclinical Studies and Clinical Trials

Since the first pioneering studies using antisense oligonucleotides (ASOs) in the late 1970s, thousands of publications followed, demonstrating the remarkableness of antisense action and its enormous application spectrum. In 1998, Fomivirsen (Vitravene) was the first, and to date the only ASO that gained approval by the US Food and Drug Administration (FDA) for intravitreous treatment of cytomegalovirus-induced retinitis in patients with acquired immune deficiency syndrome (AIDS). Meanwhile, efforts regarding ASO research decreased and investigations shifted to other molecules, e.g., small interfering RNAs, because ASO-related problems such as insufficient efficacy and off-target effects are not yet overcome. However, newer studies using ASOs with improved chemistry or approaches combining ASO treatment with other therapies, such as chemotherapy or radiation, might bring ASOs back into the spotlight. This chapter will focus on current in vivo studies and clinical trials of promising ASOs.

Komparative Evaluierung von Expressionsmustern bekannter und neuer prostatakarzinomassoziierter Gene bezüglich einer Eignung als molekularbiologische Diagnose- und Prognosefaktoren

enten beobachtet werden. Im Rahmen einer Multicenterstudie, in der die Wirksamkeit der Zoledronsäure auf die Knochenmetastasierung untersucht wurde, wurden parallel die 6 Knochenmarker tALP, bALP, NTx, CTx, ICTP, PINP im Serum von Prostatakarzinompatienten mit nachgewiesenen Knochenmetastasen gemessen [2]. Die Knochenmarker wurden vor Therapiebeginn und alle 12 Wochen bestimmt. Die Patienten mit einem gesicherten Knochenmetastasenprogress hatten im Verlauf signifikant höhere Konzentrationen von tALP, bALP, ICTP und PINP als die Patienten mit einer stabilen oder sich verbessernden Situation der Knochenmetastasen. In . Abb. 1 sind die Verläufe der Markerkonzentrationen in beiden Gruppen dargestellt. Die Knochenformationsmarker zeigten in dieser spezifischen Studie allgemein eine bessere Diskriminationsfähigkeit. Wir schlussfolgern, dass selektive Knochenmarker den Effekt der Bisphosphonat-Therapie anzeigen können und damit eine Therapieoptimierung (Fortsetzung oder Beenden) möglich ist. Die vorliegenden Untersuchungsergebnisse sowie Daten anderer Studien unterstreichen die Bedeutung der Knochenmarker in der Diagnostik und Therapie des Prostatakarzinoms. Es sollten im europäischen Maßstab prospektive Studien durchgeführt werden, die das offensichtlich erhebliche diagnostische Potenzial der Knochenmarker identifizieren und damit auch die klinische Anwendung der Serummarker absichern können. Korrespondenzadresse

In vitro and in vivo evaluation of inhibitory nucleic acid constructs for specific therapy of human urinary bladder carcinoma

D. Kunze1 · S. Füssel1 · A. Meye1 · D. Wuttig1 · K. Krämer1 · M. Kotzsch2 · M. Toma2 · B. Schwenzer3 · I. Kausch4 · D. Jocham4 · O.W. Hakenberg5 · M.O. Grimm1 · M.P. Wirth1 1 Klinik für Urologie, Medizinische Fakultät, Technische Universität Dresden, Dresden 2 Institut für Pathologie, Medizinische Fakultät, Technische Universität, Dresden 3 Professur für Allgemeine Biochemie, Technische Universität, Dresden 4 Klinik für Urologie, UKSH Campus Lübeck, Lübeck 5 Urologische Klinik und Poliklinik, Universität, Rostock