Prolonged tamoxifen exposure selects a breast cancer cell clone that is stable in vitro and in vivo

The effects of long-term tamoxifen exposure on cell growth and cell cycle kinetics were compared between oestrogen receptor (ER)-positive (MCF-7) and ER-negative (MDA-MB-231) cell lines. In the MCF-7 cell line, prolonged tamoxifen exposure (0.5 mumol/l for > 100 days) blocked cells in G0-G1 of the cell cycle, and slowed the doubling time of cells from 30 to 59 h. These effects corresponded to an increase in the cellular accumulation of tamoxifen over time [mean area under concentration curve (AUC) = 77.92 mumoles/10(6)/cells/day]. In contrast, in the MDA-MB-231 cell line, long-term tamoxifen exposure had no obvious effect on the doubling time, and reduced cellular tamoxifen accumulation (mean AUC = 50.50 mumoles/10(6)/cells/day) compared to the MCF-7 cells. Flow cytometric analysis of MDA-MB-231 cells demonstrated that a new tetraploid clone emerged following 56 days of tamoxifen exposure. Inoculation of the MDA-MB-231 tetraploid clone and MDA-MB-231 wildtype cells into the opposite flanks of athymic nude mice resulted in the rapid growth of tetraploid tumours. The tetraploid tumours maintained their ploidy following tamoxifen treatment for nine consecutive serial transplantations. Histological examination of the fifth transplant generation xenografts revealed that the tetraploid tumour had a 25-30 times greater mass, area of haemorrhage and necrosis, a slightly higher mitotic index and was more anaplastic than the control neoplasm. The control wildtype MDA-MB-231 tumours maintained a stable ploidy following tamoxifen treatment until the eighth and ninth transplantation, when a tetraploid population appeared, suggesting that tamoxifen treatment may select for this clone in vivo. These studies suggest that prolonged tamoxifen exposure may select for new, stable, fast growing cell clones in vitro as well as in vivo.     

Cell-mediated immunological responses in cervical and vaginal cancer patients immunized with a lipidated epitope of human papillomavirus type 16 E7

Human papillomavirus (HPV) infection has been causally associated with cervical cancer. We tested the effectiveness of an HLA-A*0201-restricted, HPV-16 E7 lipopeptide vaccine in eliciting cellular immune responses in vivo in women with refractory cervical cancer. In a nonrandomized Phase I clinical trial, 12 women expressing the HLA-A2 allele with refractory cervical or vaginal cancer were vaccinated with four E786-93 lipopeptide inoculations at 3-week intervals. HLA-A2 subtyping was also performed, and HPV typing was assessed on tumor specimens. Induction of epitope-specific CD8+ T-lymphocyte (CTL) responses was analyzed using peripheral blood leukapheresis specimens obtained before and after vaccination. CTL specificity was measured by IFN-gamma release assay using HLA-A*0201 matched target cells. Clinical responses were assessed by physical examination and radiographic images. All HLA-A*0201 patients were able to mount a cellular immune response to a control peptide. E786-93-specific CTLs were elicited in 4 of 10 evaluable HLA-A*0201 subjects before vaccination, 5 of 7 evaluable HLA-A*0201 patients after two vaccinations, and 2 of 3 evaluable HLA-A*0201 cultures after all four inoculations. Two of three evaluable patients' CTLs converted from unreactive to reactive after administration of all four inoculations. There were no clinical responses or treatment toxicities. The ability to generate specific cellular immune responses is retained in patients with advanced cervical cancer. Vaccination with a lipidated HPV peptide epitope appears capable of safely augmenting CTL reactivity. Although enhancements of cellular immune responses are needed to achieve therapeutic utility in advanced cervical cancer, this approach might prove useful in treating preinvasive disease.     

Semi-solid rapid compression testing of spray-formed hypereutectic Al-Si alloys

The rheology of Al-30Si-5Cu and Al-30Si-5Cu-2Mg spray-formed alloys has been characterized after holding at various times and temperatures, using semisolid rapid compression to obtain load-displacement curves. Microstructures were examined after partial remelting and compression in an attempt to understand the flow behavior. The initial resistance to flow generally increased with holding time at temperature. This increase was attributed to the increased strength of a three-dimensional (3-D) solid silicon network present in these alloys in the semisolid state, with the initial resistance to flow smaller in the magnesium-containing alloys. With increased temperature, the initial resistance decreased due to increased liquid content and grain spheroidization. The viscosity vs shear rate response was studied using the approach of Laxmanan and Flemings. The materials shear thinned rapidly during the test conditions, in which the shear rate rapidly increased from approximately 2.5 to 92 s⁻¹. The results were fitted to a power-law model, and the viscosities showed a drop of approximately two to four orders of magnitude when extrapolated to a shear rate of 1000 s⁻¹ (a typical value in actual component manufacture). The rapid compression test, which is close to conditions present in component manufacture, was shown to have more in common with a shear rate jump experiment, rather than steady-state viscometry.     

World’s largest dry gas seal marks five-year milestone

This case study covers what is believed to be the world’s largest dry-running, non-contacting gas seal, manufactured by John Crane. Recently returned for routine maintenance, it has reached its five-year anniversary while remaining in excellent condition.     

Data collection: evaluation of a pilot model

The overall purpose of this study was to explore nurses' feelings about the applicability and adequacy of a pilot model of nursing assessment (PMNA) developed for coronary care units (CCU) in order to obtain data that could help in establishing a definitive model. The evaluation, performed by 11 CCU nurses, showed that they considered the development and implementation of PMNA as valuable, and that its design was adequate for interviewing cardiac patients. These results will be employed in the elaboration of a definitive model of nursing assessment.     

A monitoring, feedback, and triggering system for reproducible breath-hold MR imaging

OBJECTIVE: To evaluate the diagnostic accuracy and clinical usefulness of high-resolution transvaginal duplex Doppler ultrasound in postpartum and post-abortion patients with excessive hemorrhage who are suspected of having residual trophoblast. METHODS: Forty-eight women with excessive hemorrhage referred for possible residual trophoblastic tissue were evaluated by transvaginal duplex Doppler ultrasonography. Based on two-dimensional imaging, the patients were divided prospectively into groups: women who had an empty uterus with a normal uterine cavity, those with a pure endometrial fluid collection and no echogenic foci, those who had a mixed endometrial fluid collection with foci of echogenicity, and those with intracavitary heterogeneous material with mixed echo patterns of fluid and solid components. In each group, Doppler studies were performed and the resistance index (RI) was calculated. The two-dimensional patterns and Doppler results were correlated with clinical and pathologic follow-up. RESULTS: Twenty-eight subjects had a normal uterine cavity and seven had a pure endometrial fluid collection; all were treated conservatively and none showed later clinical evidence of residual trophoblastic tissue. In 13 women, residual trophoblast was strongly suggested from the images of two-dimensional ultrasonography: Five showed an endometrial fluid collection with some echogenic foci, and eight exhibited intracavitary mixed echogenic material. All underwent curettage, and residual trophoblastic tissue was found in ten of the 13. The mean (+/- standard deviation) RI to flow in the myometrial arteries was 0.54 +/- 0.15 in women without residual trophoblast and 0.35 +/- 0.1 in those with residual trophoblastic tissue (P < .01). CONCLUSION: Our experience suggests that transvaginal duplex Doppler ultrasonography is an effective noninvasive method for evaluating patients with excessive postpartum and post-abortion hemorrhage who are suspected of having residual trophoblastic tissue. Its use enhances the positive preoperative diagnosis of residual trophoblastic tissue and may reduce unnecessary curettage procedures.     

Compulsory notification of cysticercosis in Ribeir?o Preto-SP, Brazil

Cysticercosis is a severe public health problem in several regions of Asia, Africa and Latin America. Epidemiologic studies based on the frequency of cases observed in specialized neurology, neurosurgery and computed tomography services, at autopsy and in seroepidemiologic studies do not permit the determination of the true prevalence of the disease in the population. The objective of the present study was to investigate the prevalence of cysticercosis by compulsory notification. The coefficient of prevalence was 54 cases/100,000 inhabitants in the municipality of Ribeir?o Preto. The results also indicated that cysticercosis is not under control in our region since 21% of cases presented the active form of the disease. Compulsory notification proved to be a valuable resource for the epidemiologic study of cysticercosis, also permitting the mapping of more affected areas for a better direction of prevention strategies.