Mutational analysis of hSNF5/INI1 and TP53 genes in choroid plexus carcinomas.

We report here the mutational analysis of hSNF5/INI1 and TP53 genes performed on 11 specimens of choroid plexus carcinomas (CPC) in which a large number of abnormalities has been detected by molecular biology techniques. Loss of heterozygosity (LOH) analysis performed on six tumors revealed losses on chromosomes 1, 3, 5, 9, 10, 13, 16, 18, and 22. However, there were no abnormalities on 17p and mutations of the TP53 gene have been observed for two tumors comprising exons 5 and 7, respectively. Exon 4 of hSNF5/INI1 was mutated in one tumor with LOH restricted to the hSNF5/INI1 locus. There was no coexistence of mutations in both analyzed genes. Our analysis confirms the presence of the hSNF5/INI1 mutations and proves involvement of TP53 mutations in sporadic cases of CPC.

CYP46: a risk factor for Alzheimer's disease or a coincidence?

Excess cholesterol is removed from the brain via hydroxylation mediated by cholesterol 24S-hydroxylase (CYP46). Although serum and cerebrospinal fluid (CSF) concentrations of 24S-hydroxycholesterol are altered during the progress of Alzheimer's disease, studies carried out to date in different populations on the association of CYP46 gene polymorphisms and risk of AD have been inconclusive. In this report, we analyzed CYP46 polymorphisms in 215 Polish AD cases and 173 healthy individuals. A fragment of CYP46 intron 2 was amplified by PCR reaction and sequenced. We discovered a new single nucleotide substitution in CYP46 intron 2, but found no difference in particular genotype or allele frequencies between AD patients and controls. However, the GG genotype of the known rs754203 polymorphic site might be a risk factor for AD, especially in APOE varepsilon4 carriers. Interestingly, in AD patients the rs754203 G allele was more frequent in males than in females. However, considering the extreme divergence of results obtained by different authors, a clear connection between the CYP46 gene and AD is questionable.

[Lymph node metastases of papillary thyroid cancer in immunohistochemical and molecular examination--preliminary report]. / Przerzuty raka brodawkowatego tarczycy (RBT) do regionalnych wezlów chlonnych w badaniu immunohistochemicznym i molekularnym--doniesienie estepne.

BACKGROUND: Total thyroidectomy with lymphadenectomy is the most typical operation in a case of papillary thyroid cancer. Range of lymph node resection still remains a matter of controversy. In some publications treatment of lymph node metastases doesn't affect survival, so only selective lymph node resection is the extended enough operation. The others remark that, local relapse- the worst prognostic factor, appears the most often in the lymph nodes, so they suggest more aggressive treatment. To solve that problem we try to find more sensitive methods to examine lymph nodes. AIM: To compare the results of detection lymph node metastases of papillary thyroid cancer by immunohistochemistry with the results of RT- PCR for thyroglobulin (Tg) mRNA. MATERIAL AND METHODS: Each of one hundred eighty four cervical lymph nodes obtained from 24 patients, operated in our Department was divided into 2 halves: one was used for conventional histopathology and immunohistochemistry, the other part was investigated by RT- PCR for Tg mRNA. Immunohistochemical staining for Tg was performed on formalin-fixed, paraffin-embedded sections with anti-Tg antibodies. RESULTS: According to routine, histopathological examination 8 (33.5%) patients had involved lymph nodes. One hundred correspondence of the results of immunohistochemistry and histopathology was observed. We obtained different results of examination of the lymph nodes in 6 (25%) patients. In four patients (16.7%) RT-PCR was more sensitive in detection of positive lymph nodes, in two patients (8.3%) it revealed less metastasized lymph nodes than immunohistochemistry. The remaining 18 patients didn't have any differences, fourteen (58.3%) of them had the negative lymph nodes and four (16.7%) had positive, the same lymph nodes in all examinations. Finally, according to RT-PCR 10 (41.7%) of the patients had metastasized lymph nodes. CONCLUSION: Tg RT-PCR is a sensitive method of detection of papillary thyroid cancer cells and may help to detect the metastases of papillary thyroid cancer in regional lymph nodes.

Enhanced P53 and BAX gene expression and apoptosis in A549 cells by cis-Pt(II) complex of 3-aminoflavone in comparison with cis-DDP.

Lung cancer remains one of the most common causes of cancer-related death worldwide. Approximately 80% is histologically non-small cell lung carcinoma (NSCLC) and in about 70% of patients it is an unresectable type. Clinical studies indicated that application of platinum derivatives caused good results and combinations of platinum with other agents could improve median survivals. In view of the central problem of sufficient efficiency of drugs in chemotherapy, efforts have focused on the development of alternative platinum-based analogues that can be more effective in cancer treatment. cis-bis(3-aminoflavone)dichloroplatinum(II) (cis-Pt(II) complex of 3-aminoflavone) represents a novel class of platinum-based potential antitumour agents. In order to evaluate the degree of apoptosis, acridine orange/ethidium bromide and Hoechst 33258/propidum iodide double staining as well as RT-PCR (P53 and BAX expression evaluation) were used in lung cancer cell line A549 after treatment with this compound in comparison with cis-diamminedichloroplatinum(II) (cis-DDP). Apoptotic cells at early and late stages and also necrotic ones were observed after usage of cis-Pt(II) complex of 3-aminoflavone and the percentage of these cells outnumbered the values obtained after cis-DDP application. The former compound induced a higher percentage of P53 and BAX expression in A549 cells in comparison with the latter one. Results indicate the beneficial properties of cis-Pt(II) complex of 3-aminoflavone as a potential antitumor drug.