A morphometric study of nucleolar organiser regions in cervical intraepithelial neoplasia

The study sought a correlation between the number of AgNOR granules and the degree of cervical intraepithelial neoplasia (CIN). Thirty-five sections (5 normal, 10 CIN1, 10 CIN2 and 10 CIN3) were subjected to retrospective analysis. The percentage of cells with 1, 2, 3, 4 and more AgNORs was calculated and the number of granules per 100 cells was counted. The number of cells containing single granules decreases. However, the number increases with CIN level when the cells contain 4 and more AgNORs. The number of granules per 100 cells also increases with the degree of CIN. It can be thus concluded that the number of cells with 4 and more AgNOR granules can serve as a CIN differentiation exponent

Prognostic significance of smac/DIABLO in endometrioid endometrial cancer.

Apoptosis may occur via a death receptor-dependent or independent (mitochondrial) pathway. The mitochondrial pathway is regulated by small molecules, such as smac/Diablo, which activates caspase cascades. This study examined smac/DIABLO expression in 76 patients with endometrioid endometrial cancers. Presence of smac/DIABLO was quantified by Western blot analysis using nonfixed fresh frozen tissues. Its appearance was found in 55 (72%) of examined tumors. Smac/DIABLO expression significantly correlated with tumor grade (

Surface TRAIL decoy receptor-4 expression is correlated with TRAIL resistance in MCF7 breast cancer cells

BACKGROUND: Tumor Necrosis Factor (TNF)-Related Apoptosis-Inducing Ligand (TRAIL) selectively induces apoptosis in cancer cells but not in normal cells. Despite this promising feature, TRAIL resistance observed in cancer cells seriously challenged the use of TRAIL as a death ligand in gene therapy. The current dispute concerns whether or not TRAIL receptor expression pattern is the primary determinant of TRAIL sensitivity in cancer cells. This study investigates TRAIL receptor expression pattern and its connection to TRAIL resistance in breast cancer cells. In addition, a DcR2 siRNA approach and a complementary gene therapy modality involving IKK inhibition (AdIKKβKA) were also tested to verify if these approaches could sensitize MCF7 breast cancer cells to adenovirus delivery of TRAIL (Ad5hTRAIL). METHODS: TRAIL sensitivity assays were conducted using Molecular Probe's Live/Dead Cellular Viability/Cytotoxicity Kit following the infection of breast cancer cells with Ad5hTRAIL. The molecular mechanism of TRAIL induced cell death under the setting of IKK inhibition was revealed by Annexin V binding. Novel quantitative Real Time RT-PCR and flow cytometry analysis were performed to disclose TRAIL receptor composition in breast cancer cells. RESULTS: MCF7 but not MDA-MB-231 breast cancer cells displayed strong resistance to adenovirus delivery of TRAIL. Only the combinatorial use of Ad5hTRAIL and AdIKKβKA infection sensitized MCF7 breast cancer cells to TRAIL induced cell death. Moreover, novel quantitative Real Time RT-PCR assays suggested that while the level of TRAIL Decoy Receptor-4 (TRAIL-R4) expression was the highest in MCF7 cells, it was the lowest TRAIL receptor expressed in MDA-MB-231 cells. In addition, conventional flow cytometry analysis demonstrated that TRAIL resistant MCF7 cells exhibited substantial levels of TRAIL-R4 expression but not TRAIL decoy receptor-3 (TRAIL-R3) on surface. On the contrary, TRAIL sensitive MDA-MB-231 cells displayed very low levels of surface TRAIL-R4 expression. Furthermore, a DcR2 siRNA approach lowered TRAIL-R4 expression on surface and this sensitized MCF7 cells to TRAIL. CONCLUSION: The expression of TRAIL-R4 decoy receptor appeared to be well correlated with TRAIL resistance encountered in breast cancer cells. Both adenovirus mediated IKKβKA expression and a DcR2 siRNA approach sensitized MCF7 breast cancer cells to TRAIL

Type II alveolar epithelial cells and free alveolar cells after intratumor TNF-a administration

The experiment used Morris hepatoma 5123 series growing in muscles of the Buffalo rats. A suspension of 3 x 1 0 ~n eoplastic cells was injected into the right hind leg of the animals. After fourteen days, TNF-a was administered into the tumour in a dose of 1 .5x104 U124 hours in 0.5 m1 PBS solution. The group 1 animals were injected for 4 days and group 11 for 8 days. Control groups consisted of rats with injected Morris hepatoma which were given PBS solution instead of TNF-a (group 111 A and B) and animals without the hepatoma, given 4 or 8 TNF-a, respectively (groups IV A and B). In the present study, we have explored the effect of intratumor TNF-a administration on the composition of cells isolated from the lungs through multiple bronchoalveolar lavages (BAL). Ultrastructural evaluation of the pulmonary tissue was done using a transmission electron microscope (TEM), with special attention paid to type 11 alveolar epithelial cells and free alveolar cells. Examinations in TEM in groups 1, 11 and IV (A and B) found, in the lumen of alveoli, an increase in the number of alveolar macrophages (AM) with morphological features of intensified activity and AM with numerous secondary lysosomes containing material of phospholipid structure. Also, numerous type 11 alveolar epithelial cells with emptied lamellar bodies were observed. The above mentioned changes were especially marked after eightfold TNF-a administration. In groups 1, 11 and IV (A and B), compared with group 111, a significant increase was found in the total number of cells isolated by BAL as well as in the number of cells with positive reaction in staining according to Beckstead's method. It may indicate that the changes in the parameters mentioned above are related to TNF-a action. The results obtained indicate the possibility of systemic effect of TNF-a after its administration into the experimental Morris hepatoma