Mycobacterial adherence and BCG treatment of superficial bladder cancer

• Published in: Progress in clinical and biological research Vol. 378; p. 75
• Main Authors: Schamhart, D H, de Boer, E C, Bevers, R F, Kurth, K H, Steerenberg, P A
• Format: Journal Article
• Language: English
• Published: United States 1992
• Subjects: Administration, Intravesical; Animals; Bacterial Adhesion - drug effects; BCG Vaccine - administration & dosage; BCG Vaccine - therapeutic use; Female; Guinea Pigs; Humans; Mycobacterium bovis - cytology; Mycobacterium bovis - drug effects; Pentosan Sulfuric Polyester - pharmacology; Rats; Urinary Bladder - microbiology; Urinary Bladder Neoplasms - therapy
• ISSN: 0361-7742

The importance of adherence of BCG (Bacillus Calmette Guerin) to the bladder wall as an initiator of the processes leading to the BCG-induced antitumor activity is still controversial. A study was initiated addressing this subject by an experimental procedure modulating BCG adherence using pretreatment with pentosan polysulphate (PPS), a polysulphated polysaccharide with glycosaminoglycan (GAG)-like properties and reported bacterial antiadherence properties to the bladder mucosa. Furthermore, PPS is applied as a drug to treat chronic and radiation induced cystitis. It was reasoned that application of PPS during BCG treatment may prevent cystitis, a common side effect. However, nothing is known about a potential interaction of PPS with the effectiveness of BCG treatment. The results obtained with guinea pigs receiving prior to each of the 6 weekly instillation with BCG-RIVM (1 x E7 cfu) an intravesical pretreatment with 10 mg PPS in 1 ml for 0.5 hours indicated an enhancement of the PPD skin reaction, inflammatory response and number of iliac lymph nodes cells after instillation 6 compared to non-pretreated animals. These results, contrary to the expected, were supported by the indication of an increased binding of [3H]uracil-labeled BCG to the bladder after PPS pretreatment. To explain these results, the binding of PPS to the bladder wall and BCG were quantitated spectrophotometrically with DMB (dimethylmethylene blue). After administration of 40 g, 80 g, and 10 mg in appropriate volumes into the rat, guinea pig & human bladder 0.9 +/- 0.3, 4.3 +/- 1.1g, and 5.7 +/- 1.8 mg PPS (n > 5) were recovered respectively, showing a strong adherence.