Superantigens are potent activators of T lymphocytes; therefore, their characteristics can be exploited in diseases where immunomodulation is known to be effective. In this study, we evaluated a new approach for the intravesical therapy of superficial bladder cancer. We investigated in coculture experiments if staphylococcal enterotoxin B (SEB)-activated PBMCs are able to induce apoptosis in human transitional cell carcinoma (TCC) cells. Additionally, we tested the toxicity and efficacy of SEB dissolved in NaCl 0.9% administered intravesically once weekly for 6 weeks in a rat bladder cancer model. To validate the coculture in vitro findings, we evaluated tumor stage, grade, apoptotic cells in the urothelium and stroma of the bladder and infiltration of the bladder wall by lymphocytes, macrophages and mononuclear cells. Coculture experiments revealed that SEB-activated PBMCs are able to kill TCC cells by inducing apoptosis. The intravesical toxicity study with a maximum dose of 100 mg/ml SEB demonstrated no side effects. In the intravesically SEB-treated animals (10 mg/ml), only 3 tumors remained vs. 15 persisting tumors in the control group. The remaining tumors of the therapy group showed a significant amount of apoptosis and granulocytes, mainly in the urothelium, whereas no relevant apoptosis or infiltration of the bladder with lymphocytes or macrophages was found in the control group. These preclinical findings suggest that SEB might be an interesting candidate for further clinical evaluation. ' 2005 Wiley-Liss, Inc.Key words: bladder cancer; superantigen; staphylococcal enterotoxin B; apoptosis; Fas ligand At initial presentation, approximately 50-70% of all bladder tumors are superficial, stage Tis (carcinoma in situ) or Ta (papillary) and T1 tumors confined to the mucosa or submucosa. 1 In the majority of these patients, tumors can be resected but have a high risk of recurrence, thus requiring adjuvant treatment. 2 The objective of intravesical therapy is to reduce recurrence or to eradicate Tis in patients when it is not possible to resect completely. The most common immunotherapeutic agent used is BCG, an attenuated strain of Mycobacterium bovis. The exact mechanism by which BCG exerts its antitumor effect remains unknown. However, cytotoxic activity of activated T lymphocytes within a complex local immune response against bladder cancer cells and secretion of several cytokines involved in the local immune response were demonstrated in in vitro cultures and in the urothelium of BCG-treated patients. [3][4][5][6] Other extremely potent activators of T lymphocytes are superantigens. Superantigens are proteins or peptide factors produced by various microorganisms like bacteria, mycoplasma or viruses. Staphylococcal enterotoxins are a family of structurally related proteins produced by Staphylococcus aureus. These compounds, m.w. 24-30 kDa, include the classical groups (A-E), the recently discovered enterotoxins G-Q and TSST-1. Streptococcal superantigens include the pyrogenic exotoxins A (and antigenic va...

The Republic of Poland joined the European Union (EU) on 1 May 2004. The EU accession brought new opportunities to the Polish health care system and the pharmaceutical market. However, there are still barriers to overcome such as bureaucracy, lack of transparency in pricing and reimbursement, decision-making processes, the short period of data exclusivity, respect for intellectual property rights, favorisation of local companies and low health care investment. Additionally, drug costs outpace overall economic development, a trend which is universally valid for almost all EU countries and which forms one of the most serious factors in health care expenditure. A systematic cost-effective assessment, the so-called fourth hurdle (after quality, efficacy and safety), of prescription drugs seems a necessity in most EU countries. The Polish Ministry of Health has defined aims for the future health care system in the National Drug Policy 2004-2008, including health economical criteria and instruments. However, it is to be expected that for some time there will be more a reimbursement hurdle instead of a fourth hurdle in controlling drug expenditure. This review focuses on the Polish pharmaceutical market with special consideration of the history of the Polish health care system. It will highlight the present situation of the Polish health care system after EU accession and provide an outlook to its possible future.

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