Bcl-2 expression as an apoptotic index in non small cell lung carcinomas.

To evaluate the bcl-2 protein expression in non small cell lung carcinomas (NSCLC) as an index of apoptosis of these tumors, in fine needle aspiration biopsies (FNABs) of the lung, we studied thirty-eight cases of NSCLC (25 bronchogenic adenocarcinomas and 13 squamous. carcinomas. Bcl-2 protein was used as the primary antibody (monoclonal, DAKO) by Alkaline-phosphatase method. Very light haematoxylin was performed as the counterstain. The results were compared and confirmed histologically. A cytoplasmatic expression of the bcl-2 protein was found in 72% (18 out of 15) of the bronchogenic adenocarcinomas while 61.54% (8 out of 13) of squamous carcinomas showed bcl-2 expression. For the quantitative analysis of our results, we used the t-test and the difference between those two histologic types was regarded as statistically significant with p < 0.001.

Nuclear grading in invasive ductal breast carcinomas.

Nuclear grade (NG) was studied in cytologic material obtained from 120 fine-needle aspiration biopsies of breast lesions and compared with the NG observed in the nuclear grade of surgical biopsies of the same lesions. All lesions included were invasive breast carcinomas diagnosed cytologically and confirmed histologically. Cytologic aspirates and tissue sections were graded by cytologists and pathologists, respectively, using a multiheaded microscope. Fisher's modification of Black's NG scheme was used. An agreement was observed between the NG of cytologic material and that of surgical biopsies in 93.33% of tumors, and an interesting exercise would be to correlate the NG with other significant factors for the prognosis of breast carcinomas. The purpose of this study was to assign and correlate the NG of ductal carcinomas of the breast in fine-needle aspiration biopsies and tissue specimens from the same patients.

The effect of lithocholic acid on proliferation and apoptosis during the early stages of colon carcinogenesis: differential effect on apoptosis in the presence of a colon carcinogen.

Lithocholic acid (LCA) is implicated in human and experimental animal carcinogenesis. Its effect on apoptosis and proliferation of the colonic epithelium was studied in a 1,2-dimethylhydrazine (DMH)-induced murine carcinogenesis model. Four groups of mice, control, LCA, DMH and DMH+LCA, were studied for 4 weeks, a period corresponding to early stages of carcinogenesis. Apoptosis (AI) and proliferation (PI) indices in the colon were determined by immunohistochemistry. LCA stimulated apoptosis [AI = 1.2 +/- 0.3% (all values are the mean +/- SEM) versus control 0.5 +/- 0.1%, P < 0. 05], as did DMH (4.3 +/- 0.8%, P < 0.02). DMH increased apoptosis at the base of the crypt nearly 50-fold, with no effect at the lumenal third. In mice receiving DMH, LCA suppressed apoptosis almost completely (0.1 +/- 0.03%); this suppression was complete at the lower two-thirds of the crypt (AI = 0) and 60% at the lumenal third. LCA increased proliferation (PI = 22.2 +/- 4.6% versus 15.4 +/- 1% in controls), but this did not reach statistical significance. DMH increased proliferation (PI = 34.6 +/- 2.3%, P < 0.01). In mice receiving DMH, proliferation (41 +/- 2.9%) was about two-thirds of the additive effect. LCA affected proliferation, mainly in the middle third of the crypt; DMH's effect was similar in distribution, but more pronounced. In mice receiving DMH, LCA shifts proliferation upward, extending it to the lumenal third of the crypt. LCA's main cell kinetic effect in the colon is on apoptosis; this effect differs in normal (stimulation) and pre-malignant colon (nearly complete suppression). LCA does not significantly stimulate proliferation in either normal or pre-malignant colon. The differential effect of LCA on apoptosis in the presence of a carcinogen partially explains its effect as a promoter on colon carcinogenesis in animal models, and may have important implications for human carcinogenesis.

Staurosporine inhibits the proliferation, alters the cell cycle distribution and induces apoptosis in HT-29 human colon adenocarcinoma cells.

Staurosporine (ST), a potent inhibitor of protein kinase C (PKC), was evaluated for its effect on the proliferation of HT-29 colon adenocarcinoma cells; PKC is associated with increased colon cell proliferation. ST inhibited cell proliferation in a time- and concentration-dependent manner by up to 90%. It also blocked the G2/M phase of the cell cycle and induced classical apoptosis (sub-diploid peak on flow cytometry, DNA ladder, and typical morphological changes). The kinetics of these changes suggest that low ST concentrations (2-20 nM) may act via a different mechanism from higher (100-1000 nM) ones. The role of ST, which is currently evaluated as an antitumor agent, in colon cancer requires further evaluation.

Selected eicosanoids increase the proliferation rate of human colon carcinoma cell lines and mouse colonocytes in vivo.

Eicosanoids have been implicated in colon carcinogenesis, but their role remains unclear. The levels of PGE2 are elevated in colon cancer tissues and in blood draining colon tumors. The effect of eicosanoids on the proliferation of colonic cells is unknown. We studied the effect of several prostaglandins (PGs) and leukotriene (LT)B4 on the proliferation rate of the human colon adenocarcinoma cell lines SW1116 and HT-29 and of 16,16-dimethyl PGE2 (dmPGE2) on the colon of BALB/c mice. PGs E2, F2 alpha, I2, the methyl ester of PGE2, dmPGE2, and LTB4 (10(-10), 10(-8), 10(-6) M), administered for up to 72 h, stimulated cell proliferation in SW1116 cells and all but PGF2 alpha and PGI2 stimulated proliferation in HT-29 cells. The proliferative effect was time- and concentration-dependent. However, in SW1116 cells the response to PGs was 'bell-shaped', being maximal at 10(-8) M, with the 10(-10) and 10(-6) M concentrations being less effective. In HT-29 cells, the addition of methyl groups to the PGE2 molecule increased the proliferative effect. None of these eicosanoids affected the distribution of these cells in the cell cycle or their rate of programmed cell death (apoptosis). dmPGE2 stimulated 3.6-fold the proliferation of colonocytes in normal BALB/c mice. This was determined by bivariate flow cytometric analysis of the expression of proliferating cell nuclear antigen (PCNA) in virtually pure populations of mouse colonocytes. dmPGE2 did not alter the cell cycle distribution of these cells. We conclude that several PGs as well as LTB4 stimulate the proliferation of human colon carcinoma cells in vitro, while dmPGE2 has a similar effect on mouse colonocytes in vivo. These findings raise the possibility that eicosanoids may contribute to colonic carcinogenesis by stimulating the proliferation rate of tumor cells in the colon.