Inhibition of Tumor Implantation by Intravesical Gemcitabine in a Murine Model of Superficial Bladder Cancer

Brocks, C.; Büttner, H.; Böhle, Andreas

doi:10.1097/01.ju.0000168657.51551.49

Cited by 47 publications

(18 citation statements)

References 19 publications

(16 reference statements)

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“…There are controversial results from studies evaluating the adjuvant role of a single, postoperative intravesical instillation of chemotherapy regimens such as epirubicin, mitomycin C and gemcitabin within 24 hours after transurethral resection (Tolley et al, 1988;Oosterlinck et al, 1993;Hall, 1997;Brocks et al, 2005 of NMIBC recommend that all patients receive one immediate instillation of chemotherapy after TUR. In patients at low risk of recurrence and progression, no further treatment is recommended prior to a subsequent recurrence.…”

Section: Introductionmentioning

confidence: 99%

Efficacy of Postoperative Bladder Irrigation with Water for Injection in Reducing Recurrence Rates of Non Muscle Invasive Bladder Cancer

Grivas¹,

Hastazeris²,

Kafarakis³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Section: Introductionmentioning

confidence: 99%

Efficacy of Postoperative Bladder Irrigation with Water for Injection in Reducing Recurrence Rates of Non Muscle Invasive Bladder Cancer

Grivas¹,

Hastazeris²,

Kafarakis³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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“…In a comparable orthotopic syngeneic murine model, tumor take rates decreased from 90 to 30% when cellular content decreased from 10 6 to 2.5 x 10 5 18 . In another model, no differences in tumor take rates were observed between 1 and 5x 10 4 instilled cells, but bladder weight significantly increased with increasing cell count together with increased amount of distant metastases and reduced animal survival 19 . In our study, reducing the amount of administered cells significantly reduced take rates to less than 20% when applying PDT, without altering take rates in the controls (Fig 2).…”

Section: Discussionmentioning

confidence: 97%

Prevention of bladder tumor implantion after fluorescence-guided TUR with photodynamic therapy

et al. 2009

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INTRODUCTIONThe prevalence of bladder cancer is very high, due to its high recurrence rate in superficial bladder cancer (30 to 85%), which is the staging of approximately 80% of the patients at first diagnosis. Risk of recurrence and progression is associated with grade, stage, presence of concomitant carcinoma in situ, size and number of lesions, as well as time to first recurrence. Recurrences can be partly attributed to new occurrences but also to residual tumors after resection. Incomplete tumor removal has been observed in 30 to 50% of TUR's, especially when dealing with T 1 or poorly visible malignant or pre-malignant disease 1 . Fluorescence guided resection with 5 amino levulinic acid (ALA) or its hexyl ester derivative (Hexvix®), has now unequivocally been demonstrated to increase detection rate and a growing number of studies indicate this has a positive impact on recurrence and progression rates 2-3 . Implantation of viable tumor cells, dispersed during resection, is a third Photodynamic Therapy: Back to the Future, edited by David H. Kessel, Proc. of SPIE Vol. 7380, 73801V · © 2009 SPIE · CCC code: 1605-7422/09/$18 · Downloaded From: http://proceedings.spiedigitallibrary.org/ on 06/15/2016 Terms of Use: http://spiedigitallibrary.org/ss/TermsOfUse.aspx factor influencing bladder cancer recurrence 4-6 . The aim of early intravesical therapy is to interfere with cell viability and thus reduce implantation risks. Photodynamic therapy (PDT) is a treatment modality that combines the use of a photosensitising molecule and light in the presence of oxygen. The first approval for Photofrin® mediated PDT was obtained for the treatment of bladder cancer in 1982. Although encouraging oncological results, PDT was abandoned due to side effects such as skin sensitisation and bladder shrinking 7 . With the venue of ALA or derivatives thereof, which are administered intravesicaly and have better tumor specificity as opposed to muscle, interest for PDT in bladder cancer treatment has regained interest 8-12 .The aim of the current paper was to investigate whether PDT immediately after fluorescence guided TUR could reduce the amount of viable intraluminal tumor cells and whether this had an impact on tumor implantation rate. MATERIAL AND METHODS Hexvix ® solution and bladder cancer cell line preparationHexvix® (hALA) (Photocure ASA,Oslo, Norway) solution at 0.8 mM was prepared in RPMI-1640 (GIBCO, Invitrogen, UK) medium supplemented with 2 % foetal calf serum (FCS) (pH 7.4) before the experiment. The tumor cell line was AY27, initially derived from carcinomas of the urinary bladder induced in female Fischer (F344). Cells were cultivated in RPMI-1640 supplemented with 10 % FCS, 5 % L-glutamine (200 mM) and 5 % penicillin-streptomycin (Biotech, GmbH, Aidenbach, Germany). Subconfluent AY-27 cells in tissue culture flasks were washed twice with PBS (pH 7.4), trypsinized (trypsin EDTA, Gibco) and collected after centrifugation. Cells (3x10 6 ) were resuspended in 164 μl Nucleofector Solution V at room temperature followed by ...

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“…Mitomycin C (MMC) is the most widely used drug for intravesical irrigation in low and intermediate risk tumors (Bouffioux et al, 1995; Sylvester, Oosterlinck & Van der Meijden, 2004), while Bacillus Calmette-Guérin (BCG) is recommended for high-risk tumors (Sylvester, Van der Meijden & Lamm, 2002; Shelley et al, 2004; Böhle & Bock, 2004). Intravesical chemotherapy with MMC is used immediately after transurethral resection of tumor (TURBT) to treat circulating tumor cells that can reimplant at other sites of the bladder, or as an ablative effect on residual tumour cells at the resection site (Pan et al, 1989; Brocks, Büttner & Böhle, 2005). MMC is also used in series of 8-weekly intravesical irrigations for patients with high risk of recurrence (Tolley et al, 1996; Sylvester, Oosterlinck & Witjes, 2008).…”

Section: Introductionmentioning

confidence: 99%

Investigation of the mechanisms of action behind Electromotive Drug Administration (EMDA)

Kos

Vásquez

Miklavčič

et al. 2016

PeerJ

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ObjectiveBladder cancer is a cause of considerable morbidity worldwide. Electromotive Drug Administration is a method that combines intravesical chemotherapy with local electric field application. Electroporation has been suggested among other mechanisms as having a possible role in the therapy, so the goal of the present study was to investigate the electric fields present in the bladder wall during the treatment to determine which mechanisms might be involved.Material and MethodsElectromotive Drug Administration involves applying intravesical mitomycin C with direct current of 20 mA delivered through a catheter electrode for 30 min. For numerical electric field computation we built a 3-D nonhomogeneous patient specific model based on CT images and used finite element method simulations to determine the electric fields in the whole body.ResultsResults indicate that highest electric field in the bladder wall was 37.7 V/m. The mean electric field magnitude in the bladder wall was 3.03 V/m. The mean magnitude of the current density in the bladder wall was 0.61 A/m2.ConclusionsThe present study shows that electroporation is not the mechanism of action in EMDA. A more likely explanation of the mechanism of action is iontophoretic forces increasing the mitomycin C concentration in the bladder wall.

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Inhibition of Tumor Implantation by Intravesical Gemcitabine in a Murine Model of Superficial Bladder Cancer

Abstract: If given early (within 30 minutes.) after tumor cell seeding, gemcitabine is effective for preventing tumor cell implantation and the resulting tumor outgrowth.

Cited by 47 publications

References 19 publications

Efficacy of Postoperative Bladder Irrigation with Water for Injection in Reducing Recurrence Rates of Non Muscle Invasive Bladder Cancer

Efficacy of Postoperative Bladder Irrigation with Water for Injection in Reducing Recurrence Rates of Non Muscle Invasive Bladder Cancer

Prevention of bladder tumor implantion after fluorescence-guided TUR with photodynamic therapy

Investigation of the mechanisms of action behind Electromotive Drug Administration (EMDA)

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