Mycobacterium Cell Wall: An Alternative to Intravesical Bacillus Calmette Guerin (BCG) Therapy in Orthotopic Murine Bladder Cancer

Chin, Joseph L.; Kadhim, Salam; Batı̇slam, Ertan; Karlik, Stephen J.; García, Bertha; Nickel, Curtis; Morales, Álvaro

doi:10.1016/s0022-5347(01)65748-3

Cited by 59 publications

(27 citation statements)

References 12 publications

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“…In the human oncology fi eld, recent interest has focused on the use of mycobacterium cell wall preparations to elicit clinical responses without a number of the undesirable side effects associated with the use of live Mycobacterium bovis strain Bacillus CalmetteGuérin (BCG) which is a standard treatment option for human bladder cancer [13][14][15][16][17]. Mycobacterium cell wall fraction (MCWF) is prepared from the non-pathogenic microorganism Mycobacterium phlei [18].…”

Section: Introductionmentioning

confidence: 99%

The in Vitro and in Vivo Anti-Cancer Potential of Mycobacterium Cell Wall Fraction (MCWF) Against Canine Transitional Cell Carcinoma of the Urinary Bladder

Filion¹,

Rodrigues²,

Johannes

et al. 2017

Acta Veterinaria

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Transitional cell carcinoma (TCC), is the most common form of urinary bladder cancer in dogs and represents 2% of all reported canine cancers. Canine TCC is usually a high-grade invasive cancer and problems associated with TCC include urinary tract obstruction and distant metastases in more than 50% of affected dogs. TCC is most commonly located in the trigone region of the bladder precluding complete surgical resection. Current treatment options for TCC in dogs include medical therapy, surgery or radiation. Mycobacterium Cell Wall Fraction (MCWF) is a biological immunomodulator derived from non-pathogenic Mycobacterium phlei. MCWF possesses a potential in multiple veterinary areas such as anticancer therapy, palliative care and treatment of infectious diseases in both small and large animals. MCWF is considered a bifunctional anti-cancer agent that induces apoptosis of cancer cells and stimulates cytokine and chemokines synthesis by cells of the immune system. Here we report the results from in vitro and in vivo studies that could suggest use of MCWF as an additional treatment option for TCC in dogs. Particularly, we demonstrated that MCWF induces a concentration dependent inhibition of proliferation of K9TCC cells which was associated with the induction of apoptosis as measured by the proteolytic activation of caspase-3 and the degradation of PARP. Furthermore, we demonstrated the safety and potential for in vivo MCWF treatment effi cacy in dogs bearing stage T2 TCC by reducing clinical signs, and improving the quality of life in dogs with TCC.

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Section: Introductionmentioning

confidence: 99%

The in Vitro and in Vivo Anti-Cancer Potential of Mycobacterium Cell Wall Fraction (MCWF) Against Canine Transitional Cell Carcinoma of the Urinary Bladder

Filion¹,

Rodrigues²,

Johannes

et al. 2017

Acta Veterinaria

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“…When tested in a murine model, mycobacterium phlei induced similar effects that are seen with BCG, namely a CD4+ T cell infiltrate when compared to control. Although the antitumor effect wasn't as significant as that seen with BCG, treatment was better tolerated overall (Chin et al, 1996).…”

Section: Mycobacterium Phleimentioning

confidence: 91%

“…This agent, has shown anti-tumor activity, is a cell wall extract, composed of carbohydrates, peptides, and lipids that is commonly found on the outer capsule of Mycobacterium phlei, a gram-positive microorganism that is located in soil, plants, and drinking water (Chin et al, 1996;& Mallick et al, 1985). Commonly prepared as a mineral oil emulsion, it has demonstrated inhibitory effects on bladder cancer cell lines through inhibition of cellular proliferation via apoptosis, as well as by an increase in the production of interleukin-12 though stimulation of cancer-infiltrating monocytes and macrophages.…”

Section: Mycobacterium Phleimentioning

confidence: 99%

Chemoprevention and Novel Treatments of Non-Muscle Invasive Bladder Cancer

Luchey¹,

Jessop²,

Oliver³

et al. 2012

Bladder Cancer - From Basic Science to Robotic Surgery

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“…4 744 984) derived from Mycobacterium phlei (M. phlei) has been shown to have anti-cancer activity. Intravesical therapy with MCWE formulated as a mineral oil emulsion (Regression®, Bioniche, London, Ontario, Canada) has been shown to reduce cancer burden in orthotopic and heterotopic murine bladder cancers (Kadhim et al, 1993;Chin et al, 1996) and in patients with carcinoma in situ of the bladder (Morales and Chin, 1997).…”

mentioning

confidence: 99%

“…MCWE is a partially delipidated and deproteinized macromolecular complex composed primarily of carbohydrates, peptides and lipids. These molecules form the basis of the two major components of the cell wall, peptidoglycan and glycolipid (Chin et al, 1996). Although the mechanism of action of MCWE against bladder cancer is unknown, M. phlei has been reported to be a potent immunostimulator active against viral and parasitic infections (Mallick et al, 1985;Tewari et al, 1996).…”

mentioning

confidence: 99%

Mycobacterium phlei cell wall complex directly induces apoptosis in human bladder cancer cells

et al. 1998

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Intact mycobacteria and mycobacterial cell wall extracts have been shown to inhibit the growth of human and murine bladder cancer. Their mechanism of action is, however, poorly understood. Mycobacterium phlei mycobacterial cell complex (MCC) is a cell wall preparation that has mycobacterial DNA in the form of short oligonucleotides complexed on the cell wall surface. In this study, we have investigated the possibility that MCC has anti-cancer activity that is mediated by two different mechanisms – a direct effect on cancer cell proliferation and viability and an indirect effect mediated by the production of interleukin 12 (IL-12), a cytokine known to possess anti-cancer activity. We have found that, although MCC is a potent inducer of IL-12 and IL-6 synthesis in monocytes and macrophages either in vitro or in vivo, it is unable to induce the synthesis of either IL-12, IL-6 or granulocyte–macrophage colony-stimulating factor (GM-CSF) by the human transitional bladder cancer cell lines HT-1197 and HT-1376. MCC is not directly cytotoxic towards these cancer cells, but induces apoptosis as determined by nuclear DNA fragmentation and by the release of nuclear mitotic apparatus protein. Mycobacterium phlei DNA associated with MCC is responsible for the induction of apoptosis. Our results indicate that MCC directly effects bladder cancer cells by inhibiting cellular proliferation through the induction of apoptosis, and has the potential for an indirect anti-cancer activity by stimulating cancer-infiltrating monocytes/macrophages to synthesize IL-12. © 1999 Cancer Research Campaign

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Mycobacterium Cell Wall: An Alternative to Intravesical Bacillus Calmette Guerin (BCG) Therapy in Orthotopic Murine Bladder Cancer

Abstract: Intravesical MCW appears to invoke a similar inflammatory response in the mouse bladder mucosa as the live BCG organism and retains an antitumor action. It deserves further evaluation as a potential antitumor agent against bladder cancer. A Phase II clinical trial is now underway.

Cited by 59 publications

References 12 publications

The in Vitro and in Vivo Anti-Cancer Potential of Mycobacterium Cell Wall Fraction (MCWF) Against Canine Transitional Cell Carcinoma of the Urinary Bladder

The in Vitro and in Vivo Anti-Cancer Potential of Mycobacterium Cell Wall Fraction (MCWF) Against Canine Transitional Cell Carcinoma of the Urinary Bladder

Chemoprevention and Novel Treatments of Non-Muscle Invasive Bladder Cancer

Mycobacterium phlei cell wall complex directly induces apoptosis in human bladder cancer cells

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