Publications & Updates

Publications from Mucpharm and Collaborative Research Groups

  1. Valle N, Eapen MS, Pillai K, Morris R, Akhter J, Mekkawy AH, Morris DL, Valle SJ. Impact of Nebulized BromAc® on Mucus Plug Clearance in a Mechanically Ventilated Ex Vivo Ovine Lung Model of Obstructive Respiratory Conditions. Life. 2024; 14(9):1111. https://doi.org/10.3390/life14091111

  2. Wajih, N., Erali, R.A., Forsythe, S.D., Schaaf, C.R., Shen, P., Levine, E.A., Soker, S., Morris, D.L. and Votanopoulos, K.I., Enhancing the Efficacy of HIPEC Through Bromelain: A Preclinical Investigation in Appendiceal Cancer. Ann Surg Oncol. May 4 2024;doi:10.1245/s10434-024-15355-0

  3. Sun, S. L., Sarofim, M., & Morris, D. L. (2024). Transhepatic Bromelain and Acetylcysteine for Treatment of Posterior Gastric Pseudomyxoma Peritonei: A Case Report. Anticancer Research, 44(5), 2239-2241.

  4. Rodriguez-Ortiz L, Vazquez-Borrego MC, Bura FI, et al. Intra-tumoural bromelain and N-acetylcysteine for recurrent and unresectable pseudomyxoma peritonei: phase I/II trial. Br J Surg. Mar 2 2024; 111(3):znae045.

  5. Pillai K, Akhter J, Mekkawy AH, Valle SJ, Morris DL. Development and Validation of Micro-Azocasein Assay for Quantifying Bromelain. Methods and Protocols. 2024; 7(2):25.

  6. Ferreira, G.M., Clarindo, F.A., Ribeiro, Á.L., Gomes-de-Pontes, L., de Carvalho, L.D., Martins-Filho, O.A., ... & Coelho-dos-Reis, J. G.A. (2023). Taming the SARS-CoV-2-mediated proinflammatory response with BromAc®. Frontiers in Immunology, 14, 1308477.

  7. Mekkawy, A.H., Breakeit, M., Pillai, K., Badar, S., Akhter, J., Valle, S.J., Morris, D.L. “Intraperitoneal BromAc® does not interfere with the healing of colon anastomosis” Cancers; 2023; 15(13):3321.

  8. Pillai, K., Mekkawy, A.H., Akhter, J., Valle, S.J., Morris, D.L. “Effect of nebulized BromAc on rheology of artificial sputum: relevance to muco-obstructive respiratory diseases” Adv Respir Med 2023; 91(2), 146-163.

  9. Wen, H.K., Valle, S.J., Morris, D.L. “Bromelain and acetylcysteine (BromAc®): a novel approach to the treatment of mucinous tumours.” Am J Cancer Res; 2023; 13(4), 1522-1532.

  10. Dong, L., Ke, K., Badar, S., Mekkawy, A.H., Akhter, J., Pillai, K., Carter, C., Morris, D.L. “A novel method for potentiation of chemotherapy in Soft Tissue Sarcomas with BromAc” Am J Transl Res 2022; 14(5): 2894-2909.

  11. dos Reis, J.G.A.C, Ferreira, G.M., Lourenço, A.A, et al. "Ex-vivo mucolytic and anti-inflammatory activity of BromAc in tracheal aspirates from COVID-19." Biomedicine & Pharmacotherapy (2022): 112753.

  12. Ke, K., Pillai, K., Mekkawy, A.H., Akhter, J., Badar, S., Valle, S.J., Morris, D.L.” Physical and Chemical Factors Affecting the Loading and Release of Bromelain from DC Beads” Am J Trans Res; 2022; 14(10):7135-7146.

  13. Dilly, A.K., Honick, B.D., Frederick, R. et al. “Improved chemosensitivity following mucolytic therapy in patient-derived models of mucinous appendix cancer”. Translational Research, 2021; 229:100-14.

  14. Carter, C.J., Pillai, K., Badar, S., Mekkawy, A.H., Akhter, J., Jefferies, T., Valle, S.J., Morris, D.L. “Dissolution of biofilm secreted by three different strains of Pseudomonas aeruginosa with bromelain, N-acetylcysteine, and their combinations” Applied Sciences. 2021; 11(23):11388.

  15. Mekkawy, A.H., Pillai, K., Suh, H., Badar, S., Akhter, J., Képénékian, V., Ke, K., Valle, S.J., Morris, D.L. “Bromelain and Acetylcysteine (BromAc) alone and in combination with Gemcitabine inhibits subcutaneous deposits of pancreatic cancer after intraperitoneal injection” Am J Trans Res;2021; 13(12): 13524-13539.

  16. Akhter, J., Quéromès, G., Pillai, K., Képénékian, V., Badar, S., Mekkawy, A.H., Frobert, E., Valle, S.J., Morris, D.L. “The Combination of Bromelain and Acetylcysteine (BromAc) Synergistically Inactivates SARS-CoV-2”. Viruses; 2021; 13(3): 425.

  17. Ke K, Pillai K, Mekkawy AH, Akhter J, Badar S, Valle SJ, & Morris DL. The effect of intraperitoneal administration of BromAc on blood parameters: phase 1 study. Discover Oncology. 2021; 12(1). 

  18. Badar, S., Azarkan, M., Mekkawy, A. H., Akhter, J., Pillai, K., El Mahyaoui, R., Ke, K., Cavanaugh, L., & Morris, D. L. Comparison of proteolytic, cytotoxic and anticoagulant properties of chromatographically fractionated bromelain to un-fractionated bromelain. Am J Trans Res, 2021; 13(5), 4309–4321. 

  19. Lam, A.R, Bazzi, K., Valle, S.J., Morris, D.L. Novel Use of Bromelain and Acetylcysteine (BromAc®) for Pleural Involvement in Pseudomyxoma Peritonei. Case Rep Oncol. 2021; 14(1):628-33.

  20. Carter, C.J., Mekkawy, A.H., Morris, D.L. “Role of human nucleoside transporters in pancreatic cancer and chemoresistance” World J Gastroenterol, 2021; 27(40):6844-6860.

  21. Mekkawy, A.H., Pillai, K., Badar, S., Akhter, J., Ke, K., Valle, S.J., & Morris, D.L. “Addition of bromelain and acetylcysteine to gemcitabine potentiates tumor inhibition in vivo in human colon cancer cell line LS174T”. Am J Cancer Res, 2021; 11(5), 2252–2263.

  22. Valle SJ, Akhter J, Mekkawy AH, Lodh S, Pillai K, Badar S, Glenn D, Power M, Liauw W, Morris DL. “A novel treatment of bromelain and acetylcysteine (BromAc™) in patients with peritoneal mucinous tumours: A phase I first in man study." Eur J Surg Oncol. 2021; 47(1):115-122.

  23. Cheng E, Sarkar A, Valle S, Morris D. “Novel use of bromelain in the management of infected prosthetic surgical mesh after ventral hernia repair”. International Journal of Abdominal Wall and Hernia Surgery. 2020; 3(1).

  24. Pillai, K., Mekkawy, A. H., Akhter, J., Badar, S., Dong, L., Liu, A. I., & Morris, D. L. “Enhancing the potency of chemotherapeutic agents by combination with bromelain and N-acetylcysteine - an in vitro study with pancreatic and hepatic cancer cells.” Am J Trans Res, 2020; 12(11), 7404–7419.

  25. Pillai, K., Akhter, J., Morris, D.L. “Assessment of a novel mucolytic solution for dissolving mucus in pseudomyxoma peritonei: an ex vivo and in vitro study.” Pleura Peritoneum. 2017 Jun 1;2(2):111-117. 

  26. Suh, H., Valle, S.J., Morris, D.L. “Targeting MUC16 in Cancer Therapy”. Chemo Open Access, 2017; 6: 235 

  27. Suh, H.; Pillai, K.; Morris, D.L. “Mucins in pancreatic cancer: Biological role, implications in carcinogenesis and applications in diagnosis and therapy”. American Journal of Cancer Research, 2017; 7:1372 – 1383 

  28. Pillai, K., Akhter, J., Mekkawy, A., Chua T.C., Morris D.L. “Physical and chemical characteristics of mucin secreted by pseudomyxoma peritonei (PMP).” Int J Med Sci. 2017; 14(1):18-28. 

  29. Masoumi-Moghaddam, S., Amini, A., and Morris, D.L. “Is mucin a determinant of peritoneal dissemination of gastrointestinal cancer? Analysis of mucin depletion in two preclinical models.” Clin Transl Oncol, 2017. 19(2): p. 261-264. 

  30. Amini, A., Masoumi-Moghaddam, S., Ehteda, A., Liauw, W.L., Morris, D.L. “Potentiation of chemotherapeutics by bromelain and N-acetylcysteine: sequential and combination therapy of gastrointestinal cancer cells.” Am J Cancer Res, 2016. 6(2): p. 350-69. 

  31. Amini, A., Masoumi-Moghaddam, S., Morris, D.L. “Utility of bromelain and N-acetylcysteine in treatment of peritoneal dissemination of gastrointestinal mucin-producing malignancies”. 2016: Springer. 

  32. Amini, A., Masoumi-Moghaddam, S., Morris, D.L. “In vivo assessment of growth-inhibitory and mucin-depleting effects of bromelain and N-acetylcysteine in peritoneal carcinomatosis models”. Annals of Oncology, 2015. 26: p. ii28. 

  33. Amini, A., Masoumi-Moghaddam, S., Ehteda, A., Liauw, W.L., Morris, D.L., “Depletion of mucin in mucin-producing human gastrointestinal carcinoma: Results from in vitro and in vivo studies with bromelain and N-acetylcysteine”. Oncotarget, 2015. 6(32): p. 33329-44. 

  34. Pillai, K., Pourgholami, M.H., Chua, T.C., Morris D.L. “MUC1 as a potential target in anticancer therapies.” American Journal of Clinical Oncology, 2015. 38(1): p. 108-118. 

  35. Amini A., Masoumi-Moghaddam S., Morris D.L. “Pseudomyxoma peritonei: Current chemotherapy and the need for mucin-directed strategies”. Expert Opinion on Orphan Drugs, 2015; 3:183 – 193. 

  36. Pillai, K., Pourgholami, M.H., Chua, T.C., Morris, D.L. Prognostic Significance of Ki67 Expression in Malignant Peritoneal Mesothelioma. American Journal of Clinical Oncology: Cancer Clinical Trials, 2015; 38:388 – 394. 

  37. Amini A., Masoumi-Moghaddam S., Ehteda, A., Morris D.L. Bromelain and N-acetylcysteine inhibit proliferation and survival of gastrointestinal cancer cells in vitro: significance of combination therapy. J Exp Clin Cancer Res, 2014. 33: p. 92. 

  38. Pillai, K., Akhter, J.A., Chua, T.C., Morris, D.L. “A formulation for in situ lysis of mucin secreted in pseudomyxoma peritonei.” Int J Cancer, 2014. 134(2): p. 478-86. 

  39. Pillai, K., Ehteda, A., Akhter, J.A., Chua, T.C., Morris, D.L. “Anticancer effect of bromelain with and without cisplatin or 5-FU on malignant peritoneal mesothelioma cells.” Anticancer Drugs, 2014. 25(2): p. 150-60. 

  40. Mekkawy, A.H., Pourgholami, M., Morris D.L. “Involvement of Urokinase-Type Plasminogen Activator System in Cancer: An Overview.” Medicinal Research Reviews, 2014; 34:918 – 956 

  41. Akhter, J.A., Pillai, K., Chua, T.C., Alzahrani, N., Morris, D.L. “Efficacy of a novel mucolytic agent on pseudomyxoma peritonei mucin, with potential for treatment through peritoneal catheters”. American Journal of Cancer Research, 2014; 4:495 – 507 

  42. Amini, A., Masoumi-Moghaddam, S., Morris, D.L. “Bromelain and N-acetylcysteine induce cytotoxic effects and reduce the expression of mucin in mucin-producing carcinoma cell lines of gastrointestinal origin”. European Journal of Cancer, 2014; 50:S43 – S43. 

  43. Pillai, K., Ehteda, A., Akhter, J., Chua, T.C., Morris, D.L. “Anticancer Effect of Bromelain Alone and In Combination with Cisplatin or Fluorouracil on Malignant Peritoneal Mesothelioma Cells”. European Journal Of Cancer, 2014; 50:E66. 

  44. Amini, A., Masoumi-Moghaddam, S., Ehteda, A., Morris, D.L. “Secreted mucins in pseudomyxoma peritonei: Pathophysiological significance and potential therapeutic prospects.” Orphanet Journal of Rare Diseases, 2014; vol. 9. 

  45. Amini, A., Masoumi-Moghaddam, S., Morris, D.L. “Bromelain and N-acetylcysteine induce cytotoxic effects and reduce the expression of mucin in mucin-producing carcinoma cell lines of gastrointestinal origin”. European Journal of Cancer, 2014; 50: S43. 

  46. Amini, A., Ehteda, A., Masoumi Moghaddam S., Akhter, J., Pillai, K., Morris, D.L. “Cytotoxic effects of bromelain in human gastrointestinal carcinoma cell lines (MKN45, KATO-III, HT29-5F12, and HT29-5M21)”. Onco Targets Ther. 2013; 6:403-9.

  47. Pillai, K., Ehteda, A., Akhter, J. Morris, D.L., “Anti-Tumour and Chemosensitising Effect of a Combination of Bromelain and N-Acetyl Cysteine with Cisplatin or 5-FU on Malignant Peritoneal Mesothelioma Cells.” J Glycobiol S, 2013. 1:p2. 

  48. Pillai, K., Akhter, J., Chua, T.C., Morris, D.L. “Anticancer property of bromelain with therapeutic potential in malignant peritoneal mesothelioma.” Cancer Invest, 2013. 31(4): p. 241-50. 

  49. Amini, A., Masoumi Moghaddam, S., Ehteda, A., Morris, D.L. “Pseudomyxoma peritonei: Uninvited goblet cells, ectopic MUC2.” 2013; Journal of Glycobiology, S1:002. 

  50. Pillai, K., Akhter, J., Chua, T.C., Morris, D.L. “Potential mucolytic agents for mucinous ascites from pseudomyxoma peritonei”. Invest New Drugs, 2012. 30(5): p. 2080-6. 

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Updates

March 2024 - USA major oncology centres MD Anderson, Mayo Clinic and UT Southwestern join clinical trial program in peritoneal malignancies

October 2023 - Principal investigator of phase 1b/2 pseudomyxoma peritonei trial in Spain presents results at the 13th International Congress on Peritoneal Surface Malignancies, Venice, Italy.

June 2023 - BromAc® reported as safe in models of hyperthermic intraperitoneal chemotherapy with mitomycin C and bowel anastomosis, supporting progression towards clinical trial of BromAc® HIPEC.

December 2022 - Promising in vitro data on the effect of BromAc® in fungal infections including Aspergillus, Candida Auris and Mucorales. Ongoing collaboration with experts in infectious diseases in Australia and internationally.

August 2022 - Last patient entered into respiratory phase 1 clinical trial of nebulised BromAc®.

June 2022 - First patient entered into respiratory phase 1 clinical trial of nebulised BromAc®.

January 2022 - Last patient treated in phase 1b trial of BromAc® in pseudomyxoma peritonei.

October 2021 - BromAc® was confirmed to be a potent mucolytic in sputum from intubated patients with COVID-19. BromAc® reduced inflammation (down regulated cytokines and chemokines). The next step for BromAc® in the respiratory program is evaluation in clinical trials.

December 2020 - United States Food & Drug Administration (FDA) pre-investigational new drug (IND) submitted for respiratory application in patients with COVID-19.

June 2020 - BromAc® prevented death in a lethal animal model of SARS-COV-2 infection and was effective in vitro in wild type and spike mutant models. BromAc® was effective against Delta and Omicron.

October 2019 - First clinical results of BromAc® in peritoneal mucinous tumours published in European Journal of Surgical Oncology.

December 2018 - United States Food & Drug Administration (FDA) accepts BromAc® as an orphan drug for patients with pseudomyxoma peritonei (mucinous peritoneal tumour).

December 2018 - European Commission adopt BromAc® orphan designations for pseudomyxoma peritonei.

November 2018 - European Medicines Agency (EMA) accepts BromAc® as an orphan drug for patients with pseudomyxoma peritonei.

August 2017 - Mucpharm Pty Ltd established in Sydney, Australia