Seize the Ribbon Research Pharmacology of Mitake/Poria Mushroom combined with Vitamin C in bladder cancer
Dr. Sensuke Konno, Ph.D.
Dr. Konno is an Associate Professor and full-time Research Director and has been conducting the multifaceted research projects since 1996 at New York medical College. Education-5/80-Pace University, White Plains, NY BS in Chemistry 5/85- New York Medical College, Valhalla, NY MS in Biochemistry 11/91-New York Medical College, Valhalla, NY Ph.D in Biochem & Mol. Bio. Dr. Konno and the urology residents have published 36 papers in the prestigious journals, made 69 presentations at the major national and international meetings and conferences, and also won over 15 awards and prizes in those meetings/conferences.
The followings are other current (on-going) research projects being performed under Dr. Konno’s supervision:
•Critical role of oxidative stress in nephrolithiasis and its potential prevention with specific antioxidants •Prevention of renal ischemic/reperfusion injury with conventional and alternative approaches and their possible mechanisms •Assessment of possible insulin-like activity of SX-fraction (mushroom extract) with hypoglycemic effect: Prophylactic modality of diabetic nephropathy •Possible improvement of chemotherapeutic efficacy with “complementary” agents in the prognostic status of ur
Dr. Konno's explanation of his research- “Bladder cancer is the second common urologic malignancy next to prostate cancer in the United States. Approximately 79,000 new cases and nearly 17,000 deaths of patients with bladder cancer are estimated this year (2017). In males, bladder cancer represents the fourth most frequent diagnosis of new cancer annually. Unfortunately, the current therapeutic options for non-muscle invasive and muscle invasive cases, are limited. For non-muscle invasive bladder cancer, endoscopic transurethral resection (TUR) is the primary modality with or without intravesical chemotherapy or immunotherapy. However, 60%-70% of patients will recur and~25% will progress to muscle invasive disease within 5 years, becoming untreatable and fatal. For muscle invasive disease, chemotherapy and surgery are the two major modalities but the prognosis is less satisfactory because only 60% of these patients will survive five years later, due to distant recurrence. In other words, no effective treatments for bladder cancer are currently yet available, even though such extensive studies have been performed over the past several decades. Seize the Ribbon support is allowing us to investigate possible anticancer effect of PE and other bioactive mushrooms in combination with vitamin C and publish papers on its effectiveness.” Background: Bladder cancer is the second common urologic malignancy next to prostate cancer in the United States. Approximately 79,000 new cases and nearly 17,000 deaths of patients with bladder cancer are estimated this year (2017). In males, bladder cancer represents the fourth most frequent diagnosis of new cancer annually. Unfortunately, the current therapeutic options for non-muscle invasive and muscle invasive cases, are limited. For non-muscle invasive bladder cancer, endoscopic transurethral resection (TUR) is the primary modality with or without intravesical chemotherapy or immunotherapy. However, 60%-70% of patients will recur and ~25% will progress to muscle invasive disease within 5 years, becoming untreatable and fatal. For muscle invasive disease, chemotherapy and surgery are the two major modalities but the prognosis is less satisfactory because only 60% of these patients will survive five years later, due to distant recurrence. In other words, no effective treatments for bladder cancer are currently yet available, even though such extensive studies have been performed over the past severaldecades. It is far overdue and there is the urgent need for a more effective, safer treatment modality with few side effects. “Conventional” therapies such as TUR, chemotherapy, immunotherapy etc. are available but rather ineffective. Intravesical administration of BCG appears to be the most effective option among them today but its severe side effects limit its use in clinical practice. Combination of 3 or 4 different chemotherapeutic drugs are also being used but some improvement with such drug combination is outweighed by palpable side effects. That is why we are more interested in “unconventional” or “alternative” therapeutic approach using various natural agents and products such as herbs, mushrooms, flowers, fruits, plant seeds, sea weeds, algae, tea, bark, shark cartilage and so forth. Actually, we are particularly interested in a bioactive mushroom extract called “PE” isolated from Poria mushroom. This mushroom is not a new mushroom but is one of well-established medicinal mushrooms, which has been used in Traditional Chinese Medicine (TCM) for 2,000 years. The reason why we are particularly interested in PE is that it may have “prooxidant” activity, capable of generating reactive oxygen species (ROS). You may not know what ROS are and what their significance in health is. You might have yet heard of “oxidative stress (OXS)”, i.e. generation of ROS that are a sort of byproducts of oxygen generated by our natural metabolic processes like breathing. In other words, as long as we use or depend on oxygen, it’s inevitable to generate these ROS. One typical type of ROS is “free radicals”, which are very active molecules with high destructive energy. Literally, they are detrimental and fatal to all kinds of cells, injuring, damaging, or killing them. I’m sure that you heard of “antioxidants” like vitamins C and E etc., which are capable of scavenging, diminishing or cleaning up these free radicals and other ROS. Anyhow, OXS is the term used to describe a destructive power of ROS to physically attack, damage/injure, or even kill the cells. Hence, has never been appreciated by any means. However, a number of studies now suggest that OXS could be considered as one of anticancer strategies to directly kill cancer cells or control cancer growth/development. It is based on the fact that cancer cells have been shown to be morevulnerable to OXS than normal counterparts. The exact reason for such higher vulnerability of cancer cells remains elusive, but at least it is believed to be the inherent difference in tissuespecific antioxidant system, i.e. the weakened or lack of antioxidant enzymes in cancer cells, which play a key role in the cellular defense system to protect cells from OXS assault. This is not the only peculiar nature of cancer cells; for instance, normal cells need oxygen to yield cellular energy (ATP) but cancer cells don’t need it, or rather, oxygen is not good for them. Anyway, taking advantage of this bizarre nature of cancer cells, it has been postulated if threshold OXS were exerted, it could be severe or strong enough to kill only cancer cells (due to weaker enzymatic activity) but not severe enough to even injure normal cells (with stronger enzymatic activity). As a result, only cancer cells could be specifically or selectively killed by OXS but normal cells would remain intact. In fact, the successful outcomes using this OXS strategy have been reported in several cancer cases. These findings are thus encouraging and tempting us to study if PE with possible prooxidant activity may have anticancer activity, inhibiting the growth of human bladder cancer cells. I am not really interested in fancy, expensive drugs, a variety of drug combinations, or novel therapeutic procedures, which thus far failed to demonstrate the expected, satisfactory outcomes. Our somewhat simple idea or strategy might be rather more worthwhile or useful in controlling bladder cancer. Simplicity could be better sometimes. Accordingly, we will investigate possible anticancer effect of PE on bladder cancer cells invitro. We will also explore how PE may work (i.e. anticancer mechanism), focusing on several key cellular/biochemical parameters. Publications:
1- Konno, S., Hsieh, T.C., Wu, J.M., Chen, Y., Chiao, J.W. and Mallouh, C.: Growth control of human prostatic cancer cells by the phorbol ester TPA: Possible involvement of protein kinases. Anticancer Res., 16: 1843-1850, 1996. 2-Oya, M.,Konno, S., Chen, Y., Tazaki, H., Mallouh, C. and Wu, J.M.: Control of cell cycle regulatory proteins and modulation of STAT1 proteins by IFN-g in human prostatic JCA-1 cells. Int. J. Oncol., 10: 835-839, 1997. 3-Konno, S., Cherry, J.P., Tazaki, H., Mallouh, C. and Chiao, J.W.: Effects of protein kinase and phosphatase inhibitors on the growth of human prostatic cancer cells. Med. Sci. Res., 25: 353-354, 1997. 4- Mordente, J.A., Konno, S., Chen, Y., Wu, J.M., Tazaki, H. and Mallouh, C.: The effects of brefeldin A (BFA) on cell cycle progression involving the modulation of the retinoblastoma protein (pRB) in PC-3 prostate cancer cells. J. Urol., 159: 275-279, 1998. 5-Mordente, J.A., Cherry, J.P., Chapman, J., Choudhury, M.S., Tazaki, H., Mallouh, C. and Konno, S.: The maturation of cathepsin D as a possible predictor of prostate cancer progression. Mol. Urol., 2: 1-5, 1998. 6- Konno, S., Mordente, J.A., Chen, Y., Wu, J.M., Tazaki, H. and Mallouh, C.: Effects of brefeldin A on androgen receptor-mediated cellular responses in human prostatic carcinoma LNCaP cells. Mol. Urol., 2: 7-11, 1998. 7- Mordente, J.A., Choudhury, M.S., Tazaki, H., Mallouh, C. and Konno, S.: Hydrolysis of androgen receptor by cathepsin D: Its biological significance in human prostate cancer. Br. J. Urol., 82: 431-435, 1998. 8-Cherry, J.P., Mordente, J.A., Chapman, J.R., Choudhury, M.S., Tazaki, H., Mallouh, C. and Konno, S.: Analysis of cathepsin D forms and their clinical implication in human prostate cancer. J. Urol., 160: 2223-2228, 1998. 9- Davidson, S.D., Cherry, J.P., Choudhury, M.S., Tazaki, H., Mallouh, C. and Konno, S.: Glyoxalase I activity in human prostate cancer: A potential marker and importance in chemotherapy. J. Urol., 161: 690-691, 1999. 10-Chapman, J.R., Tazaki, H., Mallouh, C. and Konno, S.: Mechanism of brefeldin A-induced growth inhibition and cell death in human prostatic carcinoma cells. Mol. Urol., 3: 11-16, 1999. 11-Chapman, J.R., Tazaki, H., Mallouh, C. and Konno, S.: Brefeldin A-induced apoptosis in prostatic cancer DU-145 cells: A possible p53-independent death pathway. BJU Int., 83: 703-708, 1999. 12-Samadi, A.A., Davidson, S.D., Mordente, J.A., Choudhury, M.S., Tazaki, H., Mallouh, C. and Konno, S.: Differential glycosylation of cellular prostate specific antigen and the regulatory mechanism of its secretion. Mol. Urol., 3: 147-152, 1999. 13-Won, J.H., Parekattil, S.J., Davidson, S.D., Luddy, J.S., Choudhury, M.S., Mallouh, C., Tazaki, H. and Konno, S.: Ammonium chloride-induced prostatic hypertrophy in vitro: Urinary ammonia as a potential risk factor for benign prostatic hyperplasia. Urol. Res., 27: 376-381, 1999. 14-Milanesa, D.M., Choudhury, M.S., Mallouh, C., Tazaki, H. and Konno, S.: Methylglyoxal-induced apoptosis in human prostate carcinoma: Potential modality for prostate cancer treatment. Eur. Urol., 37: 728-734, 2000. 15-Nowzari, F.B., Davidson, S.D., Eshghi, M., Mallouh, C., Tazaki, H. and Konno, S.: Adverse cellular effects of oxidative stress on renal cells and its prevention by antioxidants. Mol. Urol., 4: 15-19, 2000. 16- Fullerton, S.A., Samadi, A.A., Tortorelis, D.G., Choudhury, M.S., Mallouh, C., Tazaki, H. and Konno, S.: Induction of apoptosis in human prostatic cancer cells with b-glucan (Maitake mushroom polysaccharide). Mol. Urol., 4: 7-13, 2000. 17-Hettiarachchi, J.A., Johnson, G.B., Panageas, E., Drinis, S., Konno, S. and Das, A.K.: Malignant priapism associated with metastatic urethral carcinoma. Urol. Int., 66: 114-116, 2001. 18-Drinis, S., Finkelstein, M.P., Tortorelis, D.G., Konno, S. and Choudhury, M.S.: Five-year prognosis after radical prostatectomy in a patient with localized prostate cancer and incidental non-Hodgkin’s lymphoma. Urol. Int., 66: 105-107, 2001. 19-Samadi, A.A., Fullerton, S.A., Tortorelis, D.G., Johnson, G.B., Davidson, S.D., Choudhury, M.S., Mallouh, C., Tazaki, H. and Konno, S.: Glyoxalase I phenotype as a potential risk factor for prostate carcinoma. Urology, 57: 183-187, 2001. 20-Konno, S., Cherry, J.P., Mordente, J.A., Chapman, J.R., Choudhury, M.S., Mallouh, C. and Tazaki, H.: Role of cathepsin D in prostate cancer cell growth and its regulation by brefeldin A. World J. Urol. 19: 234-239, 2001. 21-Konno, S., Tortorelis, D.G., Fullerton, S.A., Samadi, A.A., Hettiarachchi, J.A. and Tazaki, H.: A possible hypoglycaemic effect of maitake mushroom on type 2 diabetic patients. Diabetic Med., 18: 1010, 2001. 22-Finkelstein, M.P., Drinis, S., Tortorelis, D.G., Lafaro, R.J., Konno, S. and Choudhury, M.S.: Recurrence of renal cell carcinoma with extensive vena caval thrombus three years after radical nephrectomy. Urol. Int., 68: 199-201, 2002. 23-Davidson, S.D., Milanesa, D.M., Mallouh, C., Choudhury, M.S., Tazaki, H. and Konno, S.: A possible regulatory role of glyoxalase I in cell viability of human prostate cancer. Urol. Res., 30: 116-121, 2002. 24-Hettiarachchi, J.A., Samadi, A.A., Konno, S. and Das, A.K.: Holmium laser enucleation for large (>100 ml) prostate glands. Int. J. Urol., 9: 233-236, 2002. 25-Aynehchi, S., Samadi, A.A., Gallo, S.J., Konno, S., Tazaki, H. and Eshghi, M.: Salvage extracorporeal shockwave lithotripsy after failed distal ureteroscopy. J. Endourol., 16: 355-358, 2002. 26-Konno, S., Aynehchi, S., Dolin, D.J., Schwartz, A.M., Choudhury, M.S. and Tazaki, H.: Anticancer and hypoglycemic effects of polysaccharides in edible and medicinal maitake mushroom [Grifola frondosa (Dicks.: Fr.) S.F. Gray]. Int. J. Med. Mushrooms, 4: 185-195, 2002. 27- Finkelstein, M.P., Aynehchi, S., Samadi, A.A., Drinis, S., Choudhury, M.S., Tazaki, H. and Konno, S.: Chemosensitization of carmustine with maitake b-glucan on androgen-independent prostatic cancer cells: Involvement of glyoxalase I. J. Altern. Complement. Med., 8: 573-580, 2002. 28- Hettiarachchi, J.A., Finkelstein, M.P., Schwartz, A.M., Johnson, G.B., Konno, S. and Choudhury, M.S.: Benign retroperitoneal schwannoma presenting as a giant adrenal tumor. Urol. Int., 71: 231-232, 2003. 29-Pyo, P., Louie, B., Rajamahanty, S., Choudhury, M. and Konno, S.: Possible immunotherapeutic potentiation with D-fraction in prostate cancer cells. J. Hematol. Oncol., 1: 25-33, 2008. 30- Rajamahanty, S., Louie, B., O’Neill, C., Choudhury, M. and Konno, S.: Possible disease remission in patient with invasive bladder cancer with D-fraction regimen. Int. J. Gen. Med., 2: 15-17, 2009. 31-Cang, S., Feng, J., Konno, S., Han, L., Liu, K., Sharma, S.C., Choudhury, M. and Chiao, J.W.: Deficient histone acetylation and excessive deacetylase activity as epigenomic marks of prostate cancer cells. Int. J. Oncol., 35: 1417-1422, 2009. 32- Louie, B., Rajamahanty, S., Pyo, P., Choudhury, M. and Konno, S.: Mode of cytotoxic action of nephrotoxic agents: oxidative stress and glutathione-dependent enzyme. BJU Int., 105: 264-268, 2010. 33-Rajamahanty, S., Alonzo, C., Aynehchi, S., Choudhury, M. and Konno, S.: Growth inhibition of androgen-responsive prostate cancer cells with brefeldin A targeting cell cycle and androgen receptor. J. Biomed. Sci., 17: 5-10, 2010. 34- Louie, B., Rajamahanty, S., Won, J., Choudhury, M. and Konno, S.: Synergistic potentiation of interferon activity with D-fraction on bladder cancer cells. BJU Int., 105: 1011-1015, 2010. 35-Davalos, M., Konno, S., Eshghi, M. and Choudhury, M.: Oxidative renal cell injury induced by calcium oxalate crystal and renoprotection with antioxidants: a possible role of oxidative stress in nephrolithiasis. J. Endourol., 24: 339-345, 2010. 36- Alexander, B., Fishman, A., Green, D., Choudhury, M. and Konno, S.: Attenuation of androgenic regulation by brefeldin A in androgen-responsive prostate cancer cells. Urol. Oncol. (Accepted for publication, 2010) 37-Bobby Alexander, Erin Grantham, John Phillips. “Complications of Robotic-Assisted Laparoscopic Surgery: Iatrogenic and Doulogenic” in Complications of Laparoscopic and Robotic Urologic Surgery. New York, Berlin, Springer Science, 2010. 38-Alexander B, Fishman AI, Green DA, Choudhury MS, Konno S. Attenuation of Androgenic Regulation by Brefeldin A in Androgen-Responsive Prostate Cancer Cells. Urol Oncol. 2011 July 25. Freilich DA, Nguyen HT, Phillips JL. “Factors influencing residents’ pursuit of urology fellowships.” Urology. 2011; 78 (5): 9862. 39-Fishman AI, Alexander B, Eshghi M, Choudhury MS, Konno S. Nephrotoxin-Induced Renal Cell Injury Involving Biochemical Alterations and Its Prevention with Antioxidant. J Clin Med Res. April 2012 ;4(2):95-101 40-Fishman AI, Johnson B, Won J, Alexander B, Choudhury M, Konno S. Additively Enhanced Antiproliferative Effect of Interferon Combined with Proanthocyanidin on Bladder Cancer Cells. J of Cancer. March 2012; 3: 107-112. 41-Grasso M, Fishman AI, Cohen J, Alexander B. Ureteroscopic and Extirpative Treatment of Upper Urinary Tract Urothelial Carcinoma: 15 Year Comprehensive Review of 160 Consecutive Patients. BJU Int. December 2012; 110(11):1618-26. 42-Prabharasuth D, Moses KA, Bernstein M, Dalbagni G, Herr H. Bladder Cancer After Renal Transplantation. Urology. 2013, 81: 813-819. 43-Moses KA, Bochner BH, Prabharasuth D, Sfakianos JP, Bernstein M, Herr HW, Dalbagni G. Radical Cystectomy and Orthotopic Urinary Reconstruction in Patients with Bladder Cancer following Renal Transplantation: Clinical Outcomes and Description of Technique. Transplant Proc. 2013; 4: 1661-1666. 44-Konno S, Alexander B, Freilich D, Choudhury M. Improved Anticancer Effects on Various Cancers with Combinations of Chemotherapeutic Drugs or Vitamin C and D-Fraction. J Cancer Therapy. June 2013; Vol 4 No 4. 45-Alexander B, Fishman AI, Eshghi M, Choudhury MS, Konno S. Induction of Cell Death in Renal Cell Carcinoma with Combination of D-fraction and Vitamin C. Integr Cancer Therapies. January 2013. 46-Konno S, Alexander B, Freilich D, Choudhury M. "Improved anticancer effects on various cancers with combinations of chemotherapeutic drugs or vitamin C and D-fraction." Journal Cancer Therapy. 2013; 4: 843-50.