Higher anti-tumour efficacy of platinum(IV) complex LA-12 is associated with its ability to bypass M-phase entry block induced in oxaliplatin-treated human colon cancer cells.

OBJECTIVES: Therapeutic potential of conventionally used platinum-based drugs in treatment of colorectal tumours has been limited due to high incidence of tumour resistance to them and to their severe side effects. This evokes a search for more suitable anti-cancer drugs. We have compared ability of oxaliplatin and a novel platinum(IV) complex, LA-12, to modulate the cell cycle and induce apoptosis in human colon adenocarcinoma HCT116 wt and p53/p21 null cells, and have investigated molecular mechanisms involved. MATERIALS AND METHODS: Cell cycle-related changes were analysed by flow cytometry (bromodeoxyuridine/propidium iodide staining, histone H3 phosphorylation). Apoptosis was detected using flow cytometry (assays monitoring caspase activity) and fluorescence microscopy (nuclear morphology). Changes in levels of genes/proteins involved in cell cycle and apoptosis regulation were examined by RT-PCR and western blotting. RESULTS: Our results highlight the outstanding ability of LA-12 to induce effective elimination of colon cancer cells independently of p53/p21, and in significantly lower doses compared to oxaliplatin. While oxaliplatin induced p53- and p21-dependent G2 -phase arrest associated with downregulation of cyclin B1 and Cdk1, LA-12 allowed cells to enter M-phase of the cell cycle regardless of p53/p21 status. CONCLUSIONS: Higher malignant cell toxicity and ability to bypass cell cycle arrest important for the cell damage repair suggest LA-12 to be a more effective candidate for elimination of colon tumours from a variety of genetic backgrounds, compared with oxaliplatin.

[The preparation of anticancer vaccine for patients with multiple myeloma on the base of monoclonal immunoglobulin loaded dendritic cells]. / Príprava protinádorové vakcíny pro pacienty s mnohocetným myelomem na bázi dendritických bunek nalozených monoklonálním imunoglobulinem.

BACKGROUND: On June 2006, phase II clinical trial focused on anticancer vaccination of multiple myeloma patients, was started. On September 2007, the immune and clinical response evaluation of first four patients was finished.The anticancer vaccine contained dendritic cells loaded with monoclonal immunoglobulin produced by myeloma cells. METHODS AND PATIENTS: Within the frame of phase II clinical trial were vaccinated four myeloma patients with stable disease. It was administered six vaccines for each patient, monthly. The dendritic cells were cultured from the patient's peripheral blood mononuclear cells and loaded with autologous monoclonal immunoglobulin under the good manufacturing practice conditions. After the safety and quality control, the satisfactory vaccine was administered to the patient. The functional characteristic of dendritic cells was evaluated using flow cytometry, the immune response was evaluated using ELISpot. The clinical response was monitored using monoclonal immunoglobulin concentration in patient's sera. RESULTS AND CONCLUSION: The immune response detected using ELISpot was observed in 3/4 patients. The monoclonal immunoglobulin concentration was changeable for all twelve months, but never exceeded the range of 25% for minimal clinical response achievement. During the vaccination, no significant toxicities or negative side-effects were observed. The clinical trial is going on with vaccination other patients with multiple myeloma.

The possible role of human cytomegalovirus (HCMV) in the origin of atherosclerosis.

BACKGROUND: The biological properties of some herpesviruses such as the ability of latent persistency in the host cells and the presence of viral DNA in atherosclerotic lesions, suggest the possible role of herpesviruses in the development of atherosclerosis. Although many authors proved the presence of viral DNA in arterial wall tissue, the role of herpesviruses in the origin and progress of atherogenesis still remains unclear. OBJECTIVES: The aim of this study was to confirm the presence of viral DNA in arterial wall and to associate the presence of these viruses with the development of atherosclerosis in patients with ischemic heart disease (IHD). STUDY DESIGN: A possible role of HCMV, EBV and HHV6 in the development of atherosclerosis was tested in 244 IHD patients and 87 coronarographically negative controls. The presence of viral DNA in aortic and venous walls, as well as in a peripheral blood samples was tested by the use of polymerase chain reaction (PCR) accompanied by, immunological tests for anti-virus antibodies IgM and IgG types for all experimental groups. RESULTS: The genomic DNA of HCMV was found in 76 and 59%, DNA of EBV in 59 and 50%, and DNA of HHV6 in 0.08 and 0.0%, of arterial walls of IHD patients and non-ischemic control group, respectively. No viral DNA was found in venous samples. Significant association (P < 0.01) has been proved between CMV infection and IHD. CONCLUSIONS: Our results suggest that HCMV and EBV can be found in the arterial wall, so that the arterial wall could be a potential site of persistency of those viruses. We also proved a significant association between the presence of HCMV DNA in aortic walls and atherosclerosis. Despite of the high genetic and biological similarity between CMV and HHV6 no substantial role of HHV6 in atherosclerosis has been proved.