CLINICAL APPLICATION OF GLUCAROLACTONE TO BLADDER TUMOR

I. Local Administration of Glucarolactone into Tumor Tissue

Abstract

On the basis of Boyland's hypothesis, glucaro-(1→4) (6→3)-dilactone and its diacetyl derivative (SLA) which have a potent inhibitory activity on β-glucuronidase in vivo were given orally to post-operative patients with bladder cancer. The fact that despite the inhibitory activity on urinary β-glucuronidase of these drugs recurrence occurred in a few cases, suggested the necessity of considering intrinsic factors involving susceptibility of bladder mucosa to carcinogens. Administration of glucarodilactone or SLA to patients with bladder tumor reduced plasminogen activator and lysozyme values as well as β-glucuronidase level in tumor tissue. Since the specific effect of the drug on tumor tissue was observed, studies on effects of local application of the drug on the tumor have been made. Thus, sodium glucaro-(1→4)-lactonate dissolved in water was directly injected into the tumor tissue in 46 cases.
The majority of these cases tended to show reduction in tumor size cystoscopically and resulted in an increase of fatty components of the tumor tissue. Histological characteristics of treated tumor tissue were summarized as vacuolar degeneration of cytoplasma and nuclear pyknosis of cancer cells. However, neutral fat staining (ex. Nile blue or Sudan III) revealed obviously negative. LDH-isozyme patterns of bladder tumors were examined by electrophoretic method. In general, LDH₁ and LDH₂ were increased, while LDH₄ and LDH₅ were decreased in treated tumor.