Effect of different Bacillus Calmette-Guerin substrains on growth inhibition of T24 bladder cancer cells and cytokines secretion by BCG activated peripheral blood mononuclear cells of PBMCs.

BACKGROUND: Bladder carcinoma is the most common malignancy of the urinary tract. Approximately 75-85% of patients present non-muscle invasive bladder cancer (NMIBC). Standard primary treatment for NIMBC is transurethral resection (TUR) followed by intravesical Bacillus Calmette-Guerin (BCG) immunotherapy. BCG has been accepted as the most effective agent in clinical use against NMIBC. Various BCG substrains are used worldwide for bladder cancer immunotherapy although the impact of used BCG substrain on BCG antitumor capacity is a little investigated. OBJECTIVES: The aim of this study was to compare the antitumor capacity and the ability to trigger cytokines production of three BCG substrains by stimulation of the local innate immunity in vitro. MATERIAL AND METHODS: The human bladder cancer cell line T24 was co-cultured with each of the BCG substrains: Moreau, Tice and RIVM alone or with BCG pretreated DCs (dendric cells) and allogenic PBMCs derived from the same donor. The inhibition of T24 cell growth was evaluated by 3H-thymidine incorporation. Production of Th1 cytokines (IFN-γ, TNF-α, IL-12) and Th2 cytokines (IL-10, IL-4) was measured in cultures of BCG-activated PBMCs by ELISA test. RESULTS: An approximately two-fold inhibition of T24 cell proliferation was observed as a direct cytotoxic effect of tested BCG substrains on T24 cells. However, BCG inhibited the growth of tumor cells mainly by activating the effector cells of innate immunity. About a 10-fold inhibition of T24 cell proliferation was observed when T24 cells were co-cultured with allogenic BCG pretreated DCs and PBMCs derived from the same donor. The PBMCs activated by compared live BCG substrains secreted large amounts of TNF-α and IFN-γ cytokines. CONCLUSIONS: Tested BCG substrains had little direct inhibitory effect on T24 cell proliferation. Moreau evolutionarily early BCG substrain showed similar strong, indirect antitumor effects as evolutionarily late BCG substrains Tice and RIVM.

[Efficacy and safety of vaccines against tuberculosis in the relation to genetic variability of Mycobacterium bovis BCG strains]. / Skutecznosc i bezpieczenstwo szczepionek przeciwko gruzlicy a zmiennosc genetyczna szczepów Mycobacterium bovis BCG.

All vaccines against tuberculosis used actually over the world contain Mycobacterium bovis BCG strains (Bacillus Calmette-Guerin) as active substance. Strain BCG, that was obtained in 1921 by Calmette and Guerin after 13 years ofpassaging on the potato-glicerol medium with addition of bile, was distributed to many laboratories for vaccine production. The repeated passages of M. bovis BCG strain in different culture conditions caused the numerous mutations and formation of many BCG substrains that differed according to efficacy and safety. The review of many publications related to genetic differences between BCG substrains was performed for identify the genes responsible for their virulence and protective characteristics. Possibility of development of new generation vaccines against tuberculosis is discussed.

[Prevalence of anti-HAV antibodies in Warsaw population]. / Poziom przeciwcial przeciwko wirusowemu zapaleniu watroby typu A u osób z terenu Warszawy.

The result of serological survey that was carried out on 895 subjects of Warsaw population at age 1-54 years showed the high proportion of susceptible to hepatitis A infection. It was shown about 90% susceptible among children at age 1-4 years, and about 80% among older children and adolescents aged below 19 years. The low endemicity of hepatitis A in Poland has been observed since 1997 and very low endemicity since 2002. Only 54 hepatitis A cases were reported in 2005. The morbidity was 0.18 per 100,000 habitants. Vaccination against hepatitis A by inactivated vaccine is recommended in Poland for travellers to regions that have high or intermediate endemicity of hepatitis A, for people whose employment includes production or distribution of food as well as for children and adolescents. Prevalence high proportion of susceptibles in population suggests the need of verification of the present recommendations for hepatitis A vaccination.

[HBV genotypes among patients with chronic hepatitis B in the area of central Poland]. / Genotypy HBV u pacjentów z przewleklym zapaleniem watroby typu B z terenu centralnej Polski.

At present, eight (8) HBV genotypes have been identified, marked by letters from A to H. The distribution of particular genotypes , both in the world and in Poland, is the focus of particular epidemiological interest as well as its possible association with therapeutic efficacy of patients with chronic hepatitis B (CHB) undergoing antiviral therapy. The goal of the study was HBV genotype determination among patients with CHB living in the area of central Poland. There were 65 patients (18 females and 47 males) aged 18-80 years (mean: 42.3). All of the patients had HBsAg detectable for at least 6 months and previously they did not receive any antiviral or immunomodulating therapy. HBV genotyping was performed by means of commercial method "INNO LiPA Genotyping". Genotype A was found in 56 out of 65 (86.6%) patients, genotype D in 6 out of 65 (9.2%), and mixed genoptype A+D was found in 3 out of 65 (4.6%) patients. HBeAg was detected in 49 out of 56 (87.5%) persons with genotype A, in 4 out of 6 persons with genotype D and in one person with mixed genotype A+D. Mixed genotype A+D was found only among males. Anti-HBe was found exclusively among 6 out of 56 (10.7%) persons with genotype A. Both HBeAg and anti-HBe were undetectable in one person with genotype A, in 2 persons with genotype D and in 2 persons with mixed genotype A+D. The method applied for this study is particularly suitable for the determination of mixed HBV genotypes, as well as for clinical or epidemiological studies of a large numbers of samples. Future studies to be performed after an antiviral or other form of therapy in patients with CHB may bring some evidence on the influence of treatment in relation to HBV genotype. Further studies on HBV genotypes distribution in different regions of the country may allow to gather data on molecular epidemiology of HBV infection in Poland.

Mumps in Poland since 1990 to 2003; epidemiology and antibody prevalence.

The annual incidence of mumps in Poland over the period 1990-2003 was 45-570 per 100,000 population with the epidemic peak every 4-5 years. Till 2003, mumps vaccination has not been included in the part of National Immunisation Program in Poland that comprises the obligatory vaccinations. However, mumps vaccination was recommended by National Health Authority for children at the second year of life and it could be obtained privately. The proportion of vaccinated children has increased by 50% in last years. It has influenced on decreasing of number of notified mumps cases in Poland, on lengthening of inter-epidemic period as well as on drift of infections towards older groups of children. The results of serological survey carried out on 1390 serum samples have indicated, that the proportion of positive serum samples (>11 VE/ml) was only 24.1% for children aged 1-4 years, 45.4% for children aged 5-9 years, 72.5% for age group 10-14 years, and over 85% for persons aged 15-30 years. Epidemiological data and the high proportion of individuals with negative titres of specific mumps IgG antibodies justify the need of introduction of obligatory mass immunisation against mumps in Poland.

[Prevalence of antibodies and vaccination against measles, mumps and rubella in Polish population]. / Stan uodpornienia populacji polskiej przeciw odrze, swince i rózyczce, a szczepienia ochronne.

The data according number of cases and morbidity rates of measles, mumps and rubella as well as antibody prevalence against diseases above mentioned in Polish population were shown. The impact of mass vaccination on decreasing of measles incidence and number of reported rubella congenital syndrome was observed. The possibility of elimination these diseases in the near future was discussed.

[Immunoglobulins and rules of passive-active prophylaxis]. / Immunoglobuliny oraz zasady profilaktyki czynno-biernej.

This review deals with the safety uses and mechanisms of action intravenous immunoglobulin preparations (IVIG) in prophylaxis and treatment of viruses and bacterial infection and also about the role of immunoglobulins in autoimmune disorders. The second part contains suggested intervals between immunoglobulin administration and measles immunization.