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Investigation of effects of intravesical Chemotherapeutics on Bladder Functions

Year 2012, Volume: 1 Issue: 3, 115 - 119, 01.09.2012
https://doi.org/10.5505/abantmedj.2012.85570

Abstract

OBJECTIVE: Transuretral resection is the gold standart method in superficial bladder uroepithelial tumor treatment. Intravesical chemo/immunotherapy is performed in order to prevent recurrence after transurethral resection regarding tumor level and grade, multiplicity, size and first or second time treatment. Lower urinary tract symptoms are seen in patients received intravesical chemo/immunotherapy. Mechanism and causes of these symptoms are unknown. The aim of this study is to investigate if Mitomycin C and Epirubicin, two intravesical chemotherapeutic agents, change in vitro cholinergic and purinergic responses of rat bladder smooth muscle.METHODS: In this study 30 wistar albino rats were separated in three groups each consisting of Mitomycin C group, Epirubicin group and control group. Mitomycin C group received 1 mg/ml 0.1ml intravesical Mitomycin C once a week for 8 weeks, Epirubicin group received 1 mg/ml 0.1ml intravesical Epirubicin once a week for 8 weeks, control group received 0.1 cc % 0.9 NaCl intravesical once a week for 8 weeks. One week after therapy bladder shreds was examined in vitro. Carbachole, KCL, ATP, ADP and electrical field stimulation responses were evaluated. RESULTS: There was no significant difference between Mitomycin C and Epirubicin groups with KCL, whereas Carbachole, ATP and ADP contraction responses were significantly decreased in Mitomycin C and Epirubicin groups as compred to control group. Electrical field stimulation contraction responses were not significantly different between Epirubicin and control groups. Contraction responses showed significant increase in Mitomycin C group with respect to control groups. CONCLUSION: While the decreased response to cholinergic agent and purinnergic, expected from the lack of decrease to response at contractıon alert that is obtained by the electric field warning.Increase the Mitomycin C group and the lack of change in the epirubicin group suggests that different mechanisms may play a role in this case. Further research is required on this object.

References

  • Fleshner NE, Herr HW, Stewart AK, Murphy GP, Mettlin C,Menck HR. The National Cancer Data Base report on bladder carcinoma. The American College of Surgeons Commission on Cancer and the American Cancer Society. Cancer 1996;78: 1505–13.
  • Kılavuz ES, Tosun M, Uras AR. Adequacy of nucleer matrix protein 22 to determine recurrences in pa- tients with bladder cancer. Abant Med J. 2012; 1: 18- 22.
  • Kirkali Z, Chan T, Manoharan M, et al. Bladder cancer: epidemiology, staging and grading, and diagnosis. Urology 2005;66: 4–34.
  • Babjuk M, Oosterlinck W, Sylvester R, Kaasinen E, Böhle A, Palou J. European Association of Urology guidelines on TaT1 (non-muscle invasive) bladder cancer. Update 210. Arnhem, the Netherlands: Euro- pean Association of Urology; 2010.
  • National Comprehensive Cancer Network. Clinical practice guidelines in oncology: bladder cancer in- cluding upper tract tumours and urothelial carcinoma of the prostate. Version 1. Jenkintown, PA: NCCN; 2007.
  • Sylvester RJ, van der Meijden AP, Witjes JA, et al. High grade Ta urothelial carcinoma and carcinoma in situ of the bladder. Urology 2005;66:90–107.
  • Heney NM, Koontz WW, Barton B, et al. Intravesical thiotepa versus mitomycin C in patients with Ta, T1 and TIS transitional cell carcinoma of the bladder: a phase III prospective randomized study. J Urol 1988;140:1390–3.
  • Christoper Fry, The physiology of micturition; Wom- en’s Health Medicine, 2005 (volume2) issue 6: 53-55.
  • Harriss DR, Marsh KA, Birrningham AT, et al: Expres- sion of muscarinic Mr receptors coupled to inositol phospholipid hydrolysis in human detrusor smooth muscle cells. J UroI1995;154:1241-8.
  • Burnstock G, Dumsday B, SymtheA: Atropine resistant excitation of the urinary bladder: the possibility of transmission via nerves releasing a pürine nucleotide. Br J Pharmacol. 1972 Mar ;44(3):451-61.
  • Palea S, Artibani W, Ostardo E et al: Evidence for purinergic neurotransmission in human urinary blad- der affected by interstitial cystitis. J Urol. 1993; 150:2007-12.
  • Michielsen D, Amy JJ, Coomans D, Storme G,Wyndaele JJ, Mitomycin C and epirubicin: function- al bladder damage in rats after repeat intravesical in- stillations. J.Urol.2005; 173:2166–70.
  • Post JG, te Poele JA, Oussoren Y,Stewart FA, Bladder damage in mice after single and repeated intravesical instillations of mitomycin C or doxorubicin. J Urol. 1993;150:1965-9.
  • Theobald, R. J., Jr. The effect of NG-monomethyl-L- arginine on bladder function. Eur. J. Pharmacol, 1996;311:73–78.
  • Yu Y and De Groat WC. Sensitization of pelvic afferent nerves in the in vitro urinary bladder pelvic nerve preparation of the rat by purinergic agonists or by cyclophosphamide (CYP) pretreatment. Am J Physiol Renal Physiol 2008{294}: 1146–56.
  • Patrik Aronsson, Michael Andersson, Therese Ericsson and Daniel Giglio, Assessment and Characterization of Purinergic Contractions and Relaxations in the Rat Urinary Bladder. 2010 The Authors Journal compila- tion 2010 Nordic Pharmacological Society. Basic & Clinical Pharmacology & Toxicology, 107, 603–13.
  • Ambache N, Zar MA. Non-cholinergic transmission by post-ganglionic motor neurones in the mammalian bladder. J Physiol 1970;210:761–83.
  • Somogyi GT, Zernova GV, Yoshiyama M, Yamamoto T, de Groat WC. Frequency dependence of muscarinic facilitation of transmitter release in urinary bladder strips from neurally intact or chronic spinal cord tran- sected rats. Br J Pharmacol 1998;125:241–246.
  • Wibberley A, Chen Z, Hu E, Hieble PJ, Westfal TD. Expression and functional role of ho-kinase in rat uri- nary bladder smooth muscle. Br J Pharmacol 2003;138:757–66.
  • Darblade B, Behr-Rousel D, Oger S, Effects of potassi um channel modulators on human detrusor smooth muscle myogenic phasic contractile activity: potential therapeutic targets for overactive bladder. Urology, 2006;68: 442-8.

Mesane İçi Kematerapötik İlaçların Mesane Fonksiyonu Üzerine Olan Etkileri

Year 2012, Volume: 1 Issue: 3, 115 - 119, 01.09.2012
https://doi.org/10.5505/abantmedj.2012.85570

Abstract

AMAÇ: Yüzeyel mesane üroepitelyal tümörleri tedavisinde transüretral rezeksiyon altın standarttır. Transüretral rezeksiyon sonrası gelişebilecek nüks ve ilerlemenin önlenmesi amacıyla yüzeyel mesane tümörlerinin evresine, derecesine, tek veya çok odaklı olmasına, boyutuna ve ilk ya da ikincil tedavi edilmesi gibi ölçütlere bağlı olarak intravezikal kemo/immunoterapi uygulanmaktadır. İntravezikal kemo/immunoterapi alan hastalarda alt üriner sistem semptomları sık olarak görülmektedir. Bu semptomların ortaya çıkmasının sebebi ve mekanizması bilinmemektedir. Bu çalışmadaki amacımız Mitomycin C ve Epirubicin gibi intravezikal kemoterapötik ilaçların sıçan mesane kası şeritlerinin kolinerjik ve pürinerjik ajanlara verdiği in vitro yanıtları nasıl etkilediğini araştırmaktır.YÖNTEMLER: Bu çalışmada 30 adet Wistar Albino dişi sıçan; Mitomycin C grubu, Epirubicin ve kontrol grubu olmak üzere üçe ayrıldı. Mitomycin C grubuna 8 hafta 1 mg/mL 0.1 mL intravezikal haftada 1 kez, Epirubicin grubuna 8 hafta 1 mg/mL 0.1 mL intravezikal haftada 1 kez, kontrol grubuna 8 hafta 0.1 cc % 0.9 NaCl intravezikal haftada 1 kez uygulandı. Tedavinin bitiminden 1 hafta sonra tüm gruplardan alınan mesane şeritleri in vitro olarak değerlendirildi. Karbakol, KCL, ATP, ADP ve elektriksel alan uyarısı ile oluşan kasılma yanıtlarına bakıldı. BULGULAR: Çalışma sonucunda mesane şeritlerinde in vitro olarak yapılan değerlendirmelerde kontrol grubu ile Mitomycin C ve Epirubicin grubunda KCL kasılma yanıtlarında anlamlı fark bulunmazken; Karbakol, ATP ve ADP kasılma yanıtlarında kontrole göre Mitomycin C ve Epirubicin grubunda anlamlı olarak azalmış bulundu. Elektriksel alan uyarısı ile elde edilen kasılma yanıtlarında kontrol ve Epirubicin grupları arasında anlamlı fark saptanmadı. Mitomycin C grubunda ise kontrole göre elektriksel alan uyarısı ile elde edilen kasılma yanıtlarında anlamlı artış saptandı. SONUÇ: Kolinerjik ve pürinerjik ajanlara yanıt azalmış iken elektriksel alan uyarısı ile elde edilen kasılma yanıtlarında beklenebilecek azalmanın olmaması, Mitomycin C grubunda artış olması ve Epirubicin grubunda ise değişiklik olmaması, farklı mekanizmaların bu olayda rol oynayabileceğini düşündürmektedir. Bu konu ile ilgili ileri araştırmalara gerek vardır.

References

  • Fleshner NE, Herr HW, Stewart AK, Murphy GP, Mettlin C,Menck HR. The National Cancer Data Base report on bladder carcinoma. The American College of Surgeons Commission on Cancer and the American Cancer Society. Cancer 1996;78: 1505–13.
  • Kılavuz ES, Tosun M, Uras AR. Adequacy of nucleer matrix protein 22 to determine recurrences in pa- tients with bladder cancer. Abant Med J. 2012; 1: 18- 22.
  • Kirkali Z, Chan T, Manoharan M, et al. Bladder cancer: epidemiology, staging and grading, and diagnosis. Urology 2005;66: 4–34.
  • Babjuk M, Oosterlinck W, Sylvester R, Kaasinen E, Böhle A, Palou J. European Association of Urology guidelines on TaT1 (non-muscle invasive) bladder cancer. Update 210. Arnhem, the Netherlands: Euro- pean Association of Urology; 2010.
  • National Comprehensive Cancer Network. Clinical practice guidelines in oncology: bladder cancer in- cluding upper tract tumours and urothelial carcinoma of the prostate. Version 1. Jenkintown, PA: NCCN; 2007.
  • Sylvester RJ, van der Meijden AP, Witjes JA, et al. High grade Ta urothelial carcinoma and carcinoma in situ of the bladder. Urology 2005;66:90–107.
  • Heney NM, Koontz WW, Barton B, et al. Intravesical thiotepa versus mitomycin C in patients with Ta, T1 and TIS transitional cell carcinoma of the bladder: a phase III prospective randomized study. J Urol 1988;140:1390–3.
  • Christoper Fry, The physiology of micturition; Wom- en’s Health Medicine, 2005 (volume2) issue 6: 53-55.
  • Harriss DR, Marsh KA, Birrningham AT, et al: Expres- sion of muscarinic Mr receptors coupled to inositol phospholipid hydrolysis in human detrusor smooth muscle cells. J UroI1995;154:1241-8.
  • Burnstock G, Dumsday B, SymtheA: Atropine resistant excitation of the urinary bladder: the possibility of transmission via nerves releasing a pürine nucleotide. Br J Pharmacol. 1972 Mar ;44(3):451-61.
  • Palea S, Artibani W, Ostardo E et al: Evidence for purinergic neurotransmission in human urinary blad- der affected by interstitial cystitis. J Urol. 1993; 150:2007-12.
  • Michielsen D, Amy JJ, Coomans D, Storme G,Wyndaele JJ, Mitomycin C and epirubicin: function- al bladder damage in rats after repeat intravesical in- stillations. J.Urol.2005; 173:2166–70.
  • Post JG, te Poele JA, Oussoren Y,Stewart FA, Bladder damage in mice after single and repeated intravesical instillations of mitomycin C or doxorubicin. J Urol. 1993;150:1965-9.
  • Theobald, R. J., Jr. The effect of NG-monomethyl-L- arginine on bladder function. Eur. J. Pharmacol, 1996;311:73–78.
  • Yu Y and De Groat WC. Sensitization of pelvic afferent nerves in the in vitro urinary bladder pelvic nerve preparation of the rat by purinergic agonists or by cyclophosphamide (CYP) pretreatment. Am J Physiol Renal Physiol 2008{294}: 1146–56.
  • Patrik Aronsson, Michael Andersson, Therese Ericsson and Daniel Giglio, Assessment and Characterization of Purinergic Contractions and Relaxations in the Rat Urinary Bladder. 2010 The Authors Journal compila- tion 2010 Nordic Pharmacological Society. Basic & Clinical Pharmacology & Toxicology, 107, 603–13.
  • Ambache N, Zar MA. Non-cholinergic transmission by post-ganglionic motor neurones in the mammalian bladder. J Physiol 1970;210:761–83.
  • Somogyi GT, Zernova GV, Yoshiyama M, Yamamoto T, de Groat WC. Frequency dependence of muscarinic facilitation of transmitter release in urinary bladder strips from neurally intact or chronic spinal cord tran- sected rats. Br J Pharmacol 1998;125:241–246.
  • Wibberley A, Chen Z, Hu E, Hieble PJ, Westfal TD. Expression and functional role of ho-kinase in rat uri- nary bladder smooth muscle. Br J Pharmacol 2003;138:757–66.
  • Darblade B, Behr-Rousel D, Oger S, Effects of potassi um channel modulators on human detrusor smooth muscle myogenic phasic contractile activity: potential therapeutic targets for overactive bladder. Urology, 2006;68: 442-8.
There are 20 citations in total.

Details

Primary Language Turkish
Journal Section Research Article
Authors

Sabahattin Albayrak This is me

Esat Korğalı This is me

Publication Date September 1, 2012
Published in Issue Year 2012 Volume: 1 Issue: 3

Cite

APA Albayrak, S., & Korğalı, E. (2012). Mesane İçi Kematerapötik İlaçların Mesane Fonksiyonu Üzerine Olan Etkileri. Abant Medical Journal, 1(3), 115-119. https://doi.org/10.5505/abantmedj.2012.85570
AMA Albayrak S, Korğalı E. Mesane İçi Kematerapötik İlaçların Mesane Fonksiyonu Üzerine Olan Etkileri. Abant Med J. September 2012;1(3):115-119. doi:10.5505/abantmedj.2012.85570
Chicago Albayrak, Sabahattin, and Esat Korğalı. “Mesane İçi Kematerapötik İlaçların Mesane Fonksiyonu Üzerine Olan Etkileri”. Abant Medical Journal 1, no. 3 (September 2012): 115-19. https://doi.org/10.5505/abantmedj.2012.85570.
EndNote Albayrak S, Korğalı E (September 1, 2012) Mesane İçi Kematerapötik İlaçların Mesane Fonksiyonu Üzerine Olan Etkileri. Abant Medical Journal 1 3 115–119.
IEEE S. Albayrak and E. Korğalı, “Mesane İçi Kematerapötik İlaçların Mesane Fonksiyonu Üzerine Olan Etkileri”, Abant Med J, vol. 1, no. 3, pp. 115–119, 2012, doi: 10.5505/abantmedj.2012.85570.
ISNAD Albayrak, Sabahattin - Korğalı, Esat. “Mesane İçi Kematerapötik İlaçların Mesane Fonksiyonu Üzerine Olan Etkileri”. Abant Medical Journal 1/3 (September 2012), 115-119. https://doi.org/10.5505/abantmedj.2012.85570.
JAMA Albayrak S, Korğalı E. Mesane İçi Kematerapötik İlaçların Mesane Fonksiyonu Üzerine Olan Etkileri. Abant Med J. 2012;1:115–119.
MLA Albayrak, Sabahattin and Esat Korğalı. “Mesane İçi Kematerapötik İlaçların Mesane Fonksiyonu Üzerine Olan Etkileri”. Abant Medical Journal, vol. 1, no. 3, 2012, pp. 115-9, doi:10.5505/abantmedj.2012.85570.
Vancouver Albayrak S, Korğalı E. Mesane İçi Kematerapötik İlaçların Mesane Fonksiyonu Üzerine Olan Etkileri. Abant Med J. 2012;1(3):115-9.