Skip to main content

Advertisement

Log in

Carboplatin–gemcitabine combination chemotherapy upregulates AKR1B10 expression in bladder cancer

  • Original Article
  • Published:
International Journal of Clinical Oncology Aims and scope Submit manuscript

Abstract

Background

AKR1B10 is considered to contribute to cell proliferation and chemoresistance. In the present study, we examined whether AKR1B10 expression is associated with disease-free survival in bladder cancer patients.

Methods

We obtained bladder cancer specimens from 10 patients before and after chemotherapy and measured AKR1B10 mRNA levels using real-time PCR. In addition, we conducted an immunohistochemical examination of AKR1B10 expression in 57 patients with bladder cancer before and after chemotherapy.

Results

AKR1B10 mRNA expression was significantly higher in the post-chemotherapy group than in the pre-chemotherapy group (p < 0.001). The average immunohistochemical intensity score in the pre-chemotherapy group was 0.83 ± 1.08, compared with the significantly higher score of 2.03 ± 1.03 in the post-chemotherapy group (p < 0.001). The disease-free survival rate of post-chemotherapy AKR1B10(+) patients (61.2%) was significantly lower than that of AKR1B10(−) patients (100%) (log-rank test, p = 0.039).

Conclusions

Although the present study is small and preliminary, our data suggest that post-chemotherapy AKR1B10 expression may be associated with a poor prognosis in patients who received carboplatin–gemcitabine combination chemotherapy and underwent cystectomy. Further study is warranted to elucidate its clinical significance.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Penning TM (2005) AKR1B10: a new diagnostic marker of non-small cell lung carcinoma in smokers. Clin Cancer Res 11:1687–1690

    Article  PubMed  CAS  Google Scholar 

  2. Kasajima H, Yamagishi S, Sugai S et al (2001) Enhanced in situ expression of aldose reductase in peripheral nerve and renal glomeruli in diabetic patients. Virchows Arch 439:46–54

    Article  PubMed  CAS  Google Scholar 

  3. Oates PJ (2010) Aldose reductase inhibitors and diabetic kidney disease. Curr Opin Investig Drugs 11:402–417

    PubMed  CAS  Google Scholar 

  4. Hwang YC, Kaneko M, Bakr S et al (2004) Central role for aldose reductase pathway in myocardial ischemic injury. FASEB J 18:1192–1199

    Article  PubMed  CAS  Google Scholar 

  5. Yagihashi S, Mizukami H, Ogasawara S et al (2010) The role of the polyol pathway in acute kidney injury caused by hindlimb ischaemia in mice. J Pathol 220:530–541

    Article  PubMed  Google Scholar 

  6. Cao D, Fan ST, Chung SS (1998) Identification and characterization of a novel human aldose reductase-like gene. J Biol Chem 273:11429–11435

    Article  PubMed  CAS  Google Scholar 

  7. Fukumoto S, Yamauchi N, Moriguchi H et al (2005) Overexpression of the aldo-keto reductase family protein akr1b10 is highly correlated with smokers’ non-small cell lung carcinomas. Clin Cancer Res 11:1776–1785

    Article  PubMed  CAS  Google Scholar 

  8. Yoshitake H, Takahashi M, Ishikawa H et al (2007) Aldo-keto reductase family 1, member b10 in uterine carcinomas: a potential risk factor of recurrence after surgical therapy in cervical cancer. Int J Gynecol Cancer 17:1300–1306

    Article  PubMed  CAS  Google Scholar 

  9. Heringlake S, Hofdmann M, Fiebeler A et al (2010) Identification and expression analysis of the aldo-ketoreductase1-B10 gene in primary malignant liver tumours. J Hepatol 52:220–227

    Article  PubMed  CAS  Google Scholar 

  10. Wang C, Yan R, Luo D et al (2009) Aldo-keto reductase family 1 member B10 promotes cell survival by regulating lipid synthesis and eliminating carbonyls. J Biol Chem 284:26742–26748

    Article  PubMed  CAS  Google Scholar 

  11. Martin HJ, Breyer-Pfaff U, Wsol V et al (2006) Purification and characterization of akr1b10 from human liver: role in carbonyl reduction of xenobiotics. Drug Metab Dispos 34:464–470

    Article  PubMed  CAS  Google Scholar 

  12. Koie T, Yamamoto H, Okamoto A et al (2009) Feasibility and efficacy of gemcitabine and carboplatin neoadjuvant chemotherapy in muscle-invasive bladder cancer. J Clin Oncol 27(suppl):e16100

    Google Scholar 

  13. Calvert AH, Newell DR, Gumbrell LA et al (1989) Carboplatin dosage: prospective evaluation of a simple formula based on renal function. J Clin Oncol 7:1748–1756

    PubMed  CAS  Google Scholar 

  14. Langer S, Kokozidou M, Heiss C et al (2010) Chronic kidney disease aggravates arteriovenous fistula damage in rats. Kidney Int 78:1312–1321

    Article  PubMed  Google Scholar 

  15. Takahashi M, Hoshi A, Fujii J et al (1996) Induction of aldose reductase gene expression in LEC rats during the development of the hereditary hepatitis and hepatoma. Jpn J Cancer Res 87:337–341

    Article  PubMed  CAS  Google Scholar 

  16. Zeindl-Eberhart E, Jungblut PR, Otto A et al (1997) Further characterization of a rat hepatoma-derived aldose-reductase-like protein—organ distribution and modulation in vitro. Eur J Biochem 247:792–800

    Article  PubMed  CAS  Google Scholar 

  17. Baris D, Karagas MR, Verrill C et al (2009) A case–control study of smoking and bladder cancer risk: emergent patterns over time. J Natl Cancer Inst 101:1553–1561

    Article  PubMed  Google Scholar 

  18. Kurahashi N, Inoue M, Iwasaki M et al (2009) Coffee, green tea, and caffeine consumption and subsequent risk of bladder cancer in relation to smoking status: a prospective study in Japan. Cancer Sci 100(2):294–391

    Article  PubMed  Google Scholar 

  19. Yan R, Zu X, Ma J et al (2007) Aldo-keto reductase family 1 B10 gene silencing results in growth inhibition of colorectal cancer cells: implication for cancer intervention. Int J Cancer 121:2301–2306

    Article  PubMed  CAS  Google Scholar 

Download references

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Yasuhiro Hashimoto.

About this article

Cite this article

Hashimoto, Y., Imanishi, K., Tokui, N. et al. Carboplatin–gemcitabine combination chemotherapy upregulates AKR1B10 expression in bladder cancer. Int J Clin Oncol 18, 177–182 (2013). https://doi.org/10.1007/s10147-011-0363-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10147-011-0363-7

Keywords

Navigation