Advertisement

Investigational New Drugs

, Volume 30, Issue 5, pp 2080–2086 | Cite as

Potential mucolytic agents for mucinous ascites from pseudomyxoma peritonei

  • Krishna Pillai
  • Javed Akhter
  • Terence C. Chua
  • David L. Morris
REVIEW

Summary

Pseudomyxoma peritonei is a disease characterised by the accumulation of mucinous ascites. Thus far, cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) has been shown to be effective at eradicating disease. Chemotherapy has been less effective, providing disease stabilization but not demonstrating significant treatment responses. Mucolytic is a potential class of drug that may be exploited in the chemical management of this disease. A variety of potential mucolytic agents are explored in this review providing evidence of basic biochemical evidence of its efficacy with potential translational application.

Keywords

Pseudomyxoma peritonei Cytoreductive surgery Hyperthermic intraperitoneal chemotherapy Appendix cancer Mucolysis 

Notes

Conflict of interest

None declared.

References

  1. 1.
    Moran BJ, Cecil TD (2003) The etiology, clinical presentation and management of pseudomyxoma peritonei. Surg Oncol Clin N Am 12:585–603PubMedCrossRefGoogle Scholar
  2. 2.
    Smeenk RM, van Velthuysen ML, Verwall VJ et al (2008) Appendiceal neoplasm and pseudomyxoma peritonei: a population based study. Eur J Surg Oncol 34:201–1966CrossRefGoogle Scholar
  3. 3.
    Mukerjee A, Parvaiz A, Cesil TD et al (2004) Pseudomyxoma peritonei usually originates from the appendix: a review of the evidence. Eur J Gynaecol Oncol 25:411–414Google Scholar
  4. 4.
    Yan TD, Links M, Xu ZY et al (2006) Cytoreductive surgery and perioperative intraperitoneal chemotherapy for pseudomyxoma peritonei from appendiceal mucinous neoplasm. Br J Surg 93:1270–1276PubMedCrossRefGoogle Scholar
  5. 5.
    de Bree E, Witkamp AJ, Zoetmulder FA (2000) Peroperative hyperthermic intraperitoneal chemotherapy (HIPEC) for advanced gastric cancer. Eur J Surg Oncol 26:630–632PubMedCrossRefGoogle Scholar
  6. 6.
    Smeenk RM, Bex A, Verwall VJ, Horenblas S et al (2006) Pseudomyxoma peritonei and the urinary tract: involment and treatment related complications. J Surg Oncol 93:20–23PubMedCrossRefGoogle Scholar
  7. 7.
    Bevan KE, Mohamed F, Moran BJ (2010) Pseudomyxoma peritonei. World J Gastrointest Oncol 2:44–50PubMedCrossRefGoogle Scholar
  8. 8.
    Hinson FI, Ambrose NS (1988) Pseudomyxoma peritonei. Br J Surg 85:1332–1339CrossRefGoogle Scholar
  9. 9.
    Sugarbaker PH, Chang D (1999) Results of treatment of 385 patients with peritoneal surface spread of appendiceal malignancy. Ann Surg Oncol 6:727–773PubMedCrossRefGoogle Scholar
  10. 10.
    Moran B, Barrati D, Yan TD et al (2008) Consesus statement on the loco-regional treatment of appendiceal mucinous neoplasms with peritoneal dissemination. Pseudomyxoma peritonei. J Surg Oncol 98:277–282PubMedCrossRefGoogle Scholar
  11. 11.
    Sugarbaker PH, Jablonski KA (1995) Prognostic features of 51 colorectal and 130 appendiceal cancer patients with peritoneal carcinomatosis treated with intraperitoneal hyperthermic chemotherapy. Ann Surg 221:124–132PubMedCrossRefGoogle Scholar
  12. 12.
    Guner Z, Schmidt U, Dahlke MH, Schlitt HJ et al (2005) Cytoreductive surgery and intraperitoneal chemotherapy for pseudomyxoma peritonei. Int J Colorectal Dis 20:155–160PubMedCrossRefGoogle Scholar
  13. 13.
    Duraisamy S, Kufe T, Ramasamy S, Kude D (2007) Evolution of human MUC1 oncoprotein. Int J Oncol 31:671–677PubMedGoogle Scholar
  14. 14.
    Brayman M, Thatiah A, Carson DD (2004) MUC1: a multifunctional cell surface component of reproductive tissue epithelia. Reprod Biol Endocrinol 2:4PubMedCrossRefGoogle Scholar
  15. 15.
    Duffy Mj, Shering S, Sherry M, McDermont E et al (2000) CA 15-3: a prognostic marker in breast cancer. Int J Biol Markers 15:330–333PubMedGoogle Scholar
  16. 16.
    Sachdeva M, Mo YY (2010) MicroRNA-145 supresses cell invasion and metastasis by directly targeting mucin 1. Cancer Res 70:378–387PubMedCrossRefGoogle Scholar
  17. 17.
    McGukin M, Linden SK, Sutton P et al (2011) Mucin dynamics and enteric pathogens. Nat Rev Microbiol 9:265–278CrossRefGoogle Scholar
  18. 18.
    Kim YD, Jeon JY, Woo HJ et al (2002) Interleukin -1β induces MUC2 gene expression and mucin secretion via activation of PKG-MEK/ERK and PI3K in human airway epithelial cells. J Kor Med Sci 17:765–771Google Scholar
  19. 19.
    Mejias-Luque R, Linden SK, Garrido M et al (2010) Inflammation modulates the expression of intestinal mucins MUC2 and MUC4 in gastric tumors. Oncogene 29:1753–1762PubMedCrossRefGoogle Scholar
  20. 20.
    Thornton DJ, Sheehan JK (2004) From mucins to mucus: towards a more coherent understanding of this essential barrier. Proc Am Thorac Soc 1:54–61PubMedCrossRefGoogle Scholar
  21. 21.
    Sheehan JK, Richardson PS, Fung DCK et al (1995) Analysis of respiratory mucus glycoproteins in athma: a detailed study from a patient who died in status asthmaticus. Am J Respir Cell Mol Biol 13:748–756PubMedGoogle Scholar
  22. 22.
    Mantle M, Stewart G (1989) Intetinal mucins from normal subjects and patients with cystic fibrosis: variable contents of the disulphide bound 118 kDa glycoprotein and different reactivities with an anti-(118 kDA glycoprotein) antibody. Biochem J 259:243–253PubMedGoogle Scholar
  23. 23.
    van Klinken BJW, Einerhand AWC, Buller HA et al (1998) The oligomerization of a family of four genetically clustered human gastrointestinal mucins. Glycobiology 8:67–75PubMedCrossRefGoogle Scholar
  24. 24.
    Ferreira CR, Carvalho JP, Soares FA et al (2008) Mucinous ovarian tumors associated with pseudomyxoma peritonei of adenomucinosis type: immunohistochemical evidence that they are secondary tumors. Int J Gynecol Canc 18:59–65CrossRefGoogle Scholar
  25. 25.
    Mora CS, Liu H, McAvoy T et al (2008) Psudomyxoma peritonei: is disease progression related to microbial agents? a study of bacterial, MUC2 and MUC5AC expression in disseminated peritoneal adenomucinosis and peritoneal mucinous carcinomatosis. Ann Surg Oncol 15:1414–1423CrossRefGoogle Scholar
  26. 26.
    Leir SH, Pary S, Pallag TP et al (2005) Mucin glycosylation and sulphation in airway epithelial cells is not influenced by cystic fibrosis transmembrane conductance regulator expression. Am J Respir Cell Mol Biol 32:453–461PubMedCrossRefGoogle Scholar
  27. 27.
    Thornton JM (1981) Disulphide bridges in globular proteins. J Mol Biol 151:261–287PubMedCrossRefGoogle Scholar
  28. 28.
    Lethem MI, James SL, Marriott C (1990) The role of mucous glycoproteins in rheological properties of cystic fibrosis sputum. Ann Rev Respir Dis 142:1053–1058Google Scholar
  29. 29.
    Frates RC, Ramphal R, Scharfman A et al (1993) Altyered carbohydrate composition of salivary mucins from patients with cystic fibrosis and the adhesion of pseudimonas aeruginosa. Am J Respir Cell Mol Biol 9:323–334Google Scholar
  30. 30.
    Frates RC Jr, Kaizu TT, Last JA (1983) Mucus glycoproteins secreted by respiratory epithelial tissue from cystic fibrosis patients. Pediatr Res 17:30–34PubMedCrossRefGoogle Scholar
  31. 31.
    Hill WG, Harper GS, Rozaklis T et al (1977) Sulfation of chondroitin/dermatan sulphate by cystic fibrosis pancreatic duct cells is not different from normal cells. Biochem Mol Med 62:85–94CrossRefGoogle Scholar
  32. 32.
    Smithies O (1965) Disulphide-bond cleavage and formation in proteins. Science 150:1595–1598PubMedCrossRefGoogle Scholar
  33. 33.
    Sheffner AL, Medler EM, Jacobs LW et al (1964) he invitro reduction in viscosity of human tracheobronchial secretions by acetylcysteine. Am Rev Respir Dis 90:721–729PubMedGoogle Scholar
  34. 34.
    Weller PH, Ingram D, Preece MA et al (1980) Controlled trial of intermittent aerosol therapy with sodium 2-mercaptoethane sulphonate in cystic fibrosis. Thorax 35:42–46PubMedCrossRefGoogle Scholar
  35. 35.
    Rubin BK (2007) Mucolytics, expotorants and mucokinetic medications. Respir Care 52:859–865PubMedGoogle Scholar
  36. 36.
    Wills PJ, Cole PJ (1996) Review: mucolytic and mucokinetic therapy. Pulm Pharmacol 9:197–204PubMedCrossRefGoogle Scholar
  37. 37.
    Anfinsen CB, Haber E (1961) Studies on the reduction and reformation of protein disulfide bonds. J Biochem 236:1361–1363Google Scholar
  38. 38.
    Polevoda B, Sherman F (2000) Minireview:N-terminal acetylation of eukaryotic proteins. J Biol Chem 275:36479–36482PubMedCrossRefGoogle Scholar
  39. 39.
    Matsubara M, Tathibana R, Hondo T et al (2005) Three cases of pseudomyxoma peritonei in which sodium bicarbonate was effective in removing mucus (in Japanese). Nihon Sankafujinkagakkai Kantorengo (Kanto J Obstet Gynecol) 42:427–432Google Scholar
  40. 40.
    Florence TM (1980) Degradation of protein disulphide bonds in dilute alkali. Biochem J 189:507–520PubMedGoogle Scholar
  41. 41.
    Green DE, Vande Zande HD (1981) Universal energy principal in biological systems and the unity of bioenergetics. Proc Natl Acad Sci U S A 78:5344–5347PubMedCrossRefGoogle Scholar
  42. 42.
    Shirasawa Y, Orita H, Ishida K et al (2008) Critical alkalosis following intraperitoneal irrigation with sodium bicarbonate in a patient with pseudomyxoma peritonei. J Anesth 22:278–281PubMedCrossRefGoogle Scholar
  43. 43.
    Banz V, Gajanayake T, Matozan K et al (2009) Dextran sulphate modulated MAP kinase signalling and reduces endothelial injury in a rat arotic clamping model. J Vasc Surg 50:161–170PubMedCrossRefGoogle Scholar
  44. 44.
    Sudo E, Boyd WA, King M (2000) Effect of dextran sulphate on tracheal mucociliary velocity in dogs. J Aerosol Med 13:96–97CrossRefGoogle Scholar
  45. 45.
    Balsamo R, Lanata L, Egan CG (1010) Mucoactive drugs (review). Eur Respir Rev 19:127–133CrossRefGoogle Scholar
  46. 46.
    Bahavani AL, Nisha J (2010) Dextran—the polysaccharide with versatile uses. Int J Pharm Biol Sci 1:569–573Google Scholar
  47. 47.
    Shinohara T, Misawa K, Sano H et al (2006) Pseudomyxoma peritonei due to mucinous cystadenocarcinoma in situ of the urachus presenting as inguinal hernia. Int J Clin Oncol 5:416–419CrossRefGoogle Scholar
  48. 48.
    Maeda R, Aso C, Nishikawa K et al (2007) Transient hyperglycaemia following intraperitoneal irrigation with 5% glucose in a patient with pseudomyxoma peritonei. Masiu 56:958–961Google Scholar
  49. 49.
    Roy WJ, Thomas BL, Horowitz IR (1997) Acute hyperglycaemia following intraperitoneal irrigation with 10% dextrose in a patient with pseudomyxoma peritonei. Gynaecol Oncol 65:360–362CrossRefGoogle Scholar
  50. 50.
    Sazanova IY, Houng AK, Chowdhry SA et al (2001) The mechanism ofb bacterial plasminogen activator intermediate between streptokinase and stphylokinase. J Biol Chem 276:12609–12613CrossRefGoogle Scholar
  51. 51.
    Madigan MR (1959) Correspondence; 788Google Scholar
  52. 52.
    Henke MU, Ratjen F (2007) Mucolytic in cystic fibrosis. Paediatr Respir Rev 8:24–29PubMedCrossRefGoogle Scholar
  53. 53.
    Vale JA, Meredith TJ (1981) Treatment of acetaminophen poisoning. Arch Int Med 131:394–396CrossRefGoogle Scholar
  54. 54.
    Decramer M, Rutten-van Molken M, Dekhuijzen PN et al (2005) Effects of N-acetyl cysteine on outcomes in chronic obstructive pulmonary diseases (bronchitis randomized on NAC cost utility study BRONCHUS) a randomized placebo controlled trial. Lancet 366:984Google Scholar
  55. 55.
    Tirouvanziam R, Conrad CK, Bottiglieris T et al (2006) High dose n-acetyl cysteine, a glutathione prodrug modulates inflammation in cystic fibrosis. PNAS 103:4628–4633PubMedCrossRefGoogle Scholar
  56. 56.
    Fahy JV, Dickey BT (2010) Airway mucus function & disfunction (review). New Engl J Med 368:2233–2247CrossRefGoogle Scholar
  57. 57.
    William V, Robertson B, Ropes MW et al (1941) The degradation of mucins and polysaccharides by ascorbic acid and hydrogen peroxide. (The mechanism of peroxide reaction). Biochem J 35:903–908Google Scholar
  58. 58.
    Mantle M (1991) Effect of hydrogen peroxide, mild trypsin digestion and partial reduction on rat intestinal mucin and its disulphide bond 118 kDA glycoprotein. Biochem J 274:679–685PubMedGoogle Scholar
  59. 59.
    Pillai K, Akhter J, Chua TC, et al. (2011) Mucolysis of compact PMP mucin with hydrogen peroxide and ascorbic acid. J Surg Res (in press)Google Scholar
  60. 60.
    Chua TC, Akther J, Yao P et al (2009) In vivo model of pseudomyxoma peritonei for novel candidate drug delivery. Anticancer Res 29:4051–4056PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Krishna Pillai
    • 1
  • Javed Akhter
    • 1
  • Terence C. Chua
    • 1
    • 2
    • 3
  • David L. Morris
    • 1
    • 2
    • 3
  1. 1.Department of Surgery Cancer Research LaboratoriesUniversity of New South WalesSydneyAustralia
  2. 2.UNSW Department of Surgery, St George HospitalHepatobiliary and Surgical Oncology UnitSydneyAustralia
  3. 3.St George Clinical School, Faculty of MedicineUniversity of New South WalesSydneyAustralia

Personalised recommendations