- Klinika Nowotworów Układu Moczowego, Centrum Onkologii - Instytut im. M. Skłodowskiej-Curie w Warszawie
Kierownik kliniki: dr hab. Tomasz Demkow
urinary bladder, superficial bladder carcinoma, BCG-therapy, mechanism of action, inflammation, cytotoxicity
- introduction and objectives
- BCG-therapy is generally regarded as most effective immunotherapy for superficial bladder transitional cell carcinoma. The mechanism of anti-tumor activity of BCG is not known clearly. However many studies suggest that it is dependent on specific inflammatory response in the bladder wall. Intravesical BCG therapy for superficial bladder carcinoma is considered as most effective adjuvant therapy superior to other chemotherapeutic agents.
- material and methods
- A retrospective review of the world literature using MEDLINE was performed searching for various aspects of immunological response to BCG therapy in vitro and in vivo in humans as well as in animals.
- The efficacy of BCG requires subsequent order of events starting from fibronectin ? mediated attachment of mycobacteria to bladder epithelial cells, through induction of specific panel of inflammatory cytokines (IL1, IL6, TNFa, INFg) leading to accumulation and local proliferation of BCG-sensitized cells. The final step is the generation of specific cells (BCG activated killers ? BAK cells) cytolytic against tumor. Cytotoxicity of BAK cells is attributed to the pore-forming perforins.
- The efficacy of intravesical BCG-immunotherapy bases on the sequence of immunological events leading to the developments of granulomatous inflammation in the bladder wall.
- Broghammer EL, and Ratliff TL: Immunotherapy of Urologic Tumors: Principles and Progress. Urologic Oncology 2002; 7; 45-56.
- Catalona WJ, Ratliff TL: Bacillus Calmette-Guerin & superficial bladder cancer. Clinical experience & mechanism of action. Surgery Annual 1990; 22; 363-378.
- Hillyard RW Jr, Ladaga L, and Schellhammer PF: Superficial Transitional
- Cell Carcinoma of the Bladder Associated With Mucosa Involvement of the
- Prostatic Urethra: Results of Treatment With Intravesical Bacillus
- Calmette-Guérin. J Urol 1988; 139; 290-293.
- Chapmann PB, Houghton C: Non-antibody immunotherapy of cancer. Curry Opin Immunol, 1993; 5; 726-773.
- Lamm DL, van der Meijden AP, Akaza H, Brendler C, Hedlund PO, Mizutani Y, Ratliff TL, Robinson MR, and Shinka T: Intravesical chemotherapy and immunotherapy: How do we assess their effectiveness and what are their limitations and uses? Intl J Urol 1995; 2; 23-35.
- Shapiro A, Ratliff TL, Oakley DM, Catalona WJ: Comparison of the efficacy of intravesical bacillus calmette-guerin with thiotepa, mitomycin C, poly I: C/Poly-L-Lysine and Cis platinum in murine bladder cancer. J Urol 1984; 131; 139-141.
- Krege S, Giani G Meyer R et al: A randomized multicentre trial of adjuvant therapy in superficial bladder cancer: transurethal resection only versus transurethal resection plus mitomycin C versus transurethal resection plus Bacillus Calmette- Guerin. J Urol 1996; 156; 962-696.
- Lamm DL, Blumenstein BA, Crawford ED, et al: A randomized trial of
- intravesical doxorubicin and immunotherapy with Bacille Calmette-Guérin
- for transitional-cell carcinoma of the bladder. N Engl J Med
- ; 25; 205-1210.
- Nauts HC, Fowler GA, Bogatko FH: A review of the influence of bacterial infection and of bacterial products (Coley?s toxins) on malignant tumors in man. Acta Med Scand Suppl 1953; 276; 1-103.
- Pearl R: Cancer and tuberculosis. Am J Hyg 1929; 9; 97-159.
- B. Zbar ID, Bernstein, GL Bartlett et al: Immunotherapy of cancer: regression of intradermal tumors and prevention of growth of lymph node metastases after intralesional injection of living Mycobacterium bovis. J Natl Cancer Inst 1972; 49: 119.
- Mathe G, Amiel JL, Schwarzenberg L et al: Active immunotherapy for acute lymphoblastic leukaemia. Lancet 1969 5; 1; 697-699.
- Morales A, Eidinger D, Bruce AW: Intracavity BCG in the treatment of superficial bladder tumors. J Urol 1976; 116; 180-183.
- Ratliff TL: BCG: Mechanism of action in superficial bladder cancer. Urology 1991; 37; 8-11.
- Schamahart DHJ, Kurth KHK, de Rejke TM, Vleeming R: BCG treatment and the importance of an inflammatory response. Urol Res 1992; 20; 199-203.
- Van der Meijden AP, Steerenberg PA, van Hoogstraaten IM et al: Immune reactions in patients with superficial bladder cancer after intradermal and intravesical treatment with Bacillus Calmette- Guerin. Cancer Immunol Immunother 1989; 28; 287-295.
- Glashan RW: A randomized controlled study of intravesical alpha-2b
- interferon in carcinoma in situ of the bladder. J Urol 1990; 144; 658.
- Bahnson RR, and Ratliff TL: In vitro and in vivo anti-tumor activity of recombinant mouse tumor necrosis factor (TNF) in a mouse bladder tumor (MBT-2). J Urol 1990; 144; 172-175.
- Hudson MA, Ratliff TL: Failure of intravesical interferon-alpha-2b for the treatment of patients with superficial bladder cancer previously failing intravesical BCG therapy. Urol Oncol 1995; 1; 115-118.
- Belldegrun AS, Franklin JR, O?Donnell MA, Gomella LG, Klein E, Neir Rudolph, Nseyo UO, Ratliff TL, Williams RD, and Kellihan M: Superficial bladder cancer: The role of interferon-g. J Urol 1998; 159; 1793-1801.
- Belldegrun AS, Franklin JR, O?Donnell MA et al: Superficial bladder cancer: The role of interferon-alpha. J Urol 1998; 160; 1444.
- Ratliff TL, Palmer J, McGarr J, Brown E: Intravesical bacillus calmette-guerin (BCG) therapy for murine bladder tumors: Initiation of the response by fibronectin-mediated attachment of BCG. Can Res 1987; 47; 1762-1766.
- Ratliff TL, McGarr JA, Abou-Zeid C et al: Attachment of mycobacteria to fibronectin coated surfaces. J Gen Microbiol 1988; 134; 1307-1313.
- Abou-Zeid C, Ratliff TL, Wiker HG et al: Characterization of fibronectin-binding antigens released by mycobacterium tuberculosis and mycobacterium bovis BCG. Infect and Immunity 1988; 56; 3046-3051.
- Zhao W, Schorey JS, Groger R et al: Characterization of the fibronectin binding motif for a unique mycobacterial fibronectin attachment protein, FAP. J Biol Chem 1999; 274; 4521-4526.
- Zhao W, Schorey JS, Bong-Mastek M et al: Role of a bacillus calmette-guerin fibronectin attachment protein in BCG-induced antitumor activity. Int J Cancer 2000; 86; 83-88.
- Kavoussi LR, Brown EJ, Ritchey JK, Ratliff TL: Fibronectin mediated bacillus-calmette guerin attachment to murine bladder mucosa: Requirement for the expression of an antitumor response. J Clin Invest 1990; 85; 62-67.
- Becich MJ, Carroll S, Ratliff TL: Internalization of bacille calmette-guerin by bladder tumor cells. J Urol 1991; 145; 1316-1324.
- Kuroda K, Brown EJ, Telle WB et al: Characterization of the internalization of bacillus-calmette-guerin by human bladder tumor cells. J Clin Invest 1993; 91; 69-76.
- Thalmann GN, Dewald B, Gallati H et al: Interleukin ? 4 (L-4), interleukin- 6 (IL-6), interleukin- 8 (IL-8), tumor necrosis factor- alfa, tumor necrosis factor receptors (TNFR) 55 and 75 after intravesical instillations with Bacillus Calmette- Guerin (BCG) in patients with superficial bladder cancer. J Urol 1993; 149; 337A.
- Ratliff TL, Haaff EO, and Catalona WJ: Interleukin 2 productin during intravesical BCG therapy for bladder cancer. Clin Immunol & Immunopathol 1986; 40; 375-379.
- Fleischmann JD, Toossi A, Ellner Jj et al: Urinary interleukins in patients receiving intravesical bacillus calmette-guerin therapy for superficial bladder cancer. Cancer 1989; 64; 1447-1454.
- Nadler R, Luo Y, Zhao W et al: Interleukin 10 induced augmentation of delayed-type hypersensitivity (DTH) enhances Mycobacterium bovis bacillus Calmette-Guérin (BCG) mediated antitumor activity. Clin Exp Immunol 2003; 131; 206-216.
- Saint F, Patard JJ, Maille P et al: Prognostic value of a T helper 1 urinary cytokine response after intravesical bacillus Calmette ? Guerin treatment for superficial bladder cancer. J Urol 2002; 167; 364-367.
- Ratliff TL, Gillen DP, Catalona WJ: Requirement of a thymus dependent immune response for BCG-mediated antitumor activity. J Urol 1987; 137; 155-158.
- Ratliff TL, Ritchey JK, Yuan JJJ et al: T-cell subsets required for intravesical BCG immunotherapy for bladder cancer. J Urol 1993; 150; 1018-1023.
- Lage JM, Bauer WC, Kelley DR et al: Histologic parameters and pitfalls in the interpretation of bladder biopsies in BCG treatment of superficial bladder cancer. J Urol 1986; 135; 916-919.
- Shapiro A, Ratliff TL, Oakley DM, Catalona WJ: Reduction of bladder tumor growth in mice treated with intravesical bacillus calmette-guerin and its correlation with bacillus calmette-guerin viability and natural killer cell activity. Can Res 1983; 43; 1611-1615.
- Brandau S, Riemensberger J, Jacobsen M et al: NK cells are essential for effective BCG Immunotherapy. Int J Cancer 2001; 92; 697-702.
- Taniguchi K, Koga S, Nishikido M et al: Systemic immune response after intravesicial instillation of bacille Calmette-Guerin (BCG) for superficial bladder cancer. Clin Exp Immunol 1999; 115; 131-135.
- Torrence RJ, Kavoussi LR, Catalona WJ, Ratliff TL: Prognostic factors in patients treated with bacillus calmette-guerin for superficial bladder cancer. J Urol 1988; 139; 941-944.
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