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991.
LC Hartmann DJ Schaid JE Woods TP Crotty JL Myers PG Arnold PM Petty TA Sellers JL Johnson SK McDonnell MH Frost RB Jenkins 《Canadian Metallurgical Quarterly》1999,340(2):77-84
BACKGROUND: Options for women at high risk for breast cancer include surveillance, chemoprevention, and prophylactic mastectomy. The data on the outcomes for surveillance and prophylactic mastectomy are incomplete. METHODS: We conducted a retrospective study of all women with a family history of breast cancer who underwent bilateral prophylactic mastectomy at the Mayo Clinic between 1960 and 1993. The women were divided into two groups - high risk and moderate risk - on the basis of family history. A control study of the sisters of the high-risk probands and the Gail model were used to predict the number of breast cancers expected in these two groups in the absence of prophylactic mastectomy. RESULTS: We identified 639 women with a family history of breast cancer who had undergone bilateral prophylactic mastectomy: 214 at high risk and 425 at moderate risk. The median length of follow-up was 14 years. The median age at prophylactic mastectomy was 42 years. According to the Gall model, 37.4 breast cancers were expected in the moderate-risk group; 4 breast cancers occurred (reduction in risk, 89.5 percent; P<0.001). We compared the numbers of breast cancers among the 214 high-risk probands with the numbers among their 403 sisters who had not undergone prophylactic mastectomy. Of these sisters, 38.7 percent (156) had been given a diagnosis of breast cancer (115 cases were diagnosed before the respective proband's prophylactic mastectomy, 38 were diagnosed afterward, and the time of the diagnosis was unknown in 3 cases). By contrast, breast cancer was diagnosed in 1.4 percent (3 of 214) of the probands. Thus, prophylactic mastectomy was associated with a reduction in the incidence of breast cancer of at least 90 percent. CONCLUSIONS: In women with a high risk of breast cancer on the basis of family history, prophylactic mastectomy can significantly reduce the incidence of breast cancer. 相似文献
992.
The method of additive properties was applied to the density and glass transition temperature, Tg, of linear amorphous polyurethanes. This method assumes that certain polymer properties result from the additive effects of unique constituent group properties and that these group properties are independent of their environment. To determine the component properties, 14 model polyurethanes were synthesized. The polymers contained only the following four groups: urethane, phenylene, methylene, and ether oxygen. The densities and Tg's of these polymers were measured. Using these measured values, the known composition of each polymer, and an appropriate additive from, the molar component properties were calculated using a matrix least-squares simultaneous fit algorithm. An error analysis confirmed that the component values were determined with greater accuracy than literature results. The densities ranged from 1.0 to 1.2 g/cm3 and measured versus predicted densities agreed to within 0.3% on the average. Tg's ranged from ?70°C to 70°C and measured versus predicted Tg's agreed to within 1.3% on the average. 相似文献
993.
994.
995.
Verena Boschert Jonas Teusch Urs D. A. Müller-Richter Roman C. Brands Stefan Hartmann 《International journal of molecular sciences》2022,23(2)
The enzyme pyruvate kinase M2 (PKM2) plays a major role in the switch of tumor cells from oxidative phosphorylation to aerobic glycolysis, one of the hallmarks of cancer. Different allosteric inhibitors or activators and several posttranslational modifications regulate its activity. Head and neck squamous cell carcinoma (HNSCC) is a common disease with a high rate of recurrence. To find out more about PKM2 and its modulation in HNSCC, we examined a panel of HNSCC cells using real-time cell metabolic analysis and Western blotting with an emphasis on phosphorylation variant Tyr105 and two reagents known to impair PKM2 activity. Our results show that in HNSCC, PKM2 is commonly phosphorylated at Tyrosine 105. Its levels depended on tyrosine kinase activity, emphasizing the importance of growth factors such as EGF (epidermal growth factor) on HNSCC metabolism. Furthermore, its correlation with the expression of CD44 indicates a role in cancer stemness. Cells generally reacted with higher glycolysis to PKM2 activator DASA-58 and lower glycolysis to PKM2 inhibitor Compound 3k, but some were more susceptible to activation and others to inhibition. Our findings emphasize the need to further investigate the role of PKM2 in HNSCC, as it could aid understanding and treatment of the disease. 相似文献
996.
On Regularities of the π-Electronic Structure of Heteroanalogous Polyvinylidene Compounds Starting with simple forms of the equations for the eigenvalues and eigencoefficients of the π-system of heteroanalogous polyvinylidene compounds 3 several regularities in the π-electronic structure of these systems are derived and compared with known experimental facts. In this line several predictions are given for the properties of compounds unknown up to now. 相似文献
997.
Anita K. Luu Mia Cadieux Mackenzie Wong Rachel Macdonald Robert Jones Dongsic Choi Michelle Oblak Brigitte Brisson Scott Sauer James Chafitz David Warshawsky Geoffrey A. Wood Alicia M. Viloria-Petit 《International journal of molecular sciences》2022,23(6)
Osteosarcoma (OS) is a highly malignant bone tumour that has seen little improvement in treatment modalities in the past 30 years. Understanding what molecules contribute to OS biology could aid in the discovery of novel therapies. Extracellular vesicles (EVs) serve as a mode of cell-to-cell communication and have the potential to uncover novel protein signatures. In our research, we developed a novel pipeline to isolate, characterize, and profile EVs from normal bone and osteosarcoma tissue explants from canine OS patients. Proteomic analysis of vesicle preparations revealed a protein signature related to protein metabolism. One molecule of interest, PSMD14/Rpn11, was explored further given its prognostic potential in human and canine OS, and its targetability with the drug capzimin. In vitro experiments demonstrated that capzimin induces apoptosis and reduces clonogenic survival, proliferation, and migration in two metastatic canine OS cell lines. Capzimin also reduces the viability of metastatic human OS cells cultured under 3D conditions that mimic the growth of OS cells at secondary sites. This unique pipeline can improve our understanding of OS biology and identify new prognostic markers and molecular targets for both canine and human OS patients. 相似文献
998.
Nathalie Printemps Brigitte Le Magueresse-Battistoni Sakina Mhaouty-Kodja Catherine Vigui Ccile Michel 《International journal of molecular sciences》2022,23(6)
This review provides an overview of the assessment of the endocrine disrupting (ED) properties of carbon disulfide (CS2), following the methodology used at the European level to identify endocrine disruptors. Relevant in vitro, in vivo studies and human data are analyzed. The assessment presented here focuses on one endocrine activity, i.e., thyroid disruption, and two main adverse effects, neurotoxicity and cardiotoxicity. The data available on the different ED or non-ED modes of action (MoA), known to trigger these adverse effects, are described and the strength of evidence of the different MoA is weighted. We conclude that the adverse effects could be due to systemic toxicity rather than endocrine-mediated toxicity. This assessment illustrates the scientific and regulatory challenges in differentiating a specific endocrine disruption from an indirect endocrine effect resulting from a non-ED mediated systemic toxicity. This issue of evaluating the ED properties of highly toxic and reactive substances has been insufficiently developed by European guidance so far and needs to be further addressed. Finally, this example also raises questions about the capacity of the technics available in toxicology to address such a complex issue with certainty. 相似文献
999.
1000.
Lefebvre B Diarra MS Giguère K Roy G Michaud S Malouin F 《Journal of food protection》2005,68(11):2411-2419
In a longitudinal study (165 days), we investigated the effect of growth-promoting agents (monensin and trenbolone acetate-estradiol) and an antibiotic (oxytetracycline) on the incidence in feedlot steers of Escherichia coli O157, including antibiotic-resistant and hypermutable isolates. Eighty steers in 16 pens were treated with eight combinations of promoters, and each treatment was duplicated. Fecal samples were collected at nine different sampling times for detection of E. coli O157. Overall, 50 E. coli O157 isolates were detected in treated animals, and none were found in untreated animals. Compared with untreated controls, there was a significant association between the utilization of growth-promoting agents or antibiotics and the shedding of E. coli O157 at day 137 (P = 0.03), when a prevalence peak was observed and 50% of the isolates were detected. Multiplex PCR assays were conducted for some virulence genes. PCR results indicated that all except one isolate possessed at least the Shiga toxin gene stx2. MICs for 12 antibiotics were determined, and eight oxytetracycline-resistant E. coli O157 strains were identified. Antibiotic-resistant strains were considered a distinct subpopulation of E. coli O157 by pulsed-field gel electrophoresis typing. Seven of these antibiotic-resistant strains were isolated early in the study (on or before day 25), and among them two were also hypermutable as determined by rifampin mutation frequencies. The proportion of hypermutable strains among E. coli O157 isolates remained relatively constant throughout the study period. These results indicate that the use of growth-promoting agents and antibiotics in beef production may increase the risk of environmental contamination by E. coli O157. 相似文献