ER Strategies Research Articles

Immediate Adhesive Properties to Dentin and Enamel of a Universal Adhesive Associated With a Hydrophobic Resin Coat

To evaluate the effect of acid etching and application of a hydrophobic resin coat on the enamel/dentin bond strengths and degree of conversion (DC) within the hybrid layer of a universal adhesive system (G-Bond Plus [GB]). A total of 60 extracted third molars were divided into four groups for bond-strength testing, according to the adhesive strategy: GB applied as a one-step self-etch adhesive (1-stepSE); GB applied as in 1-stepSE followed by one coat of the hydrophobic resin Heliobond (2-stepSE); GB applied as a two-step etch-and-rinse adhesive (2-stepER); GB applied as in 2-stepER followed by one coat of the hydrophobic resin Heliobond (3-stepER). There were 40 teeth used for enamel microshear bond strength (μSBS) and DC; and 20 teeth used for dentin microtensile bond strength (μTBS) and DC. After restorations were constructed, specimens were stored in water (37°C/24 h) and then tested at 0.5 mm/min (μTBS) or 1.0 mm/min (μSBS). Enamel-resin and dentin-resin interfaces from each group were evaluated for DC using micro-Raman spectroscopy. Data were analyzed with two-way analysis of variance for each substrate and the Tukey test (α=0.05). For enamel, the use of a hydrophobic resin coat resulted in statistically significant higher mean enamel μSBS only for the ER strategy (3-stepER vs 2-stepER, p<0.0002). DC was significantly improved for the SE strategy (p<0.00002). For dentin, the use of a hydrophobic resin coat resulted in significantly higher dentin mean μTBS only for the SE strategy (2-stepSE vs 1-stepSE, p<0.0007). DC was significantly improved in groups 2-stepSE and 3-stepER when compared with 1-stepSE and 2-stepER, respectively (p<0.0009). The use of a hydrophobic resin coat may be beneficial for the selective enamel etching technique, because it improves bond strengths to enamel when applied with the ER strategy and to dentin when used with the SE adhesion strategy. The application of a hydrophobic resin coat may improve DC in resin-dentin interfaces formed with either the SE or the ER strategy. On enamel, DC may benefit from the application of a hydrophobic resin coat over 1-stepSE adhesives.

Efficacy and mechanism of action of Proellex, an antiprogestin in aromatase overexpressing and Letrozole resistant T47D breast cancer cells

Aromatase inhibitors (AI) are considered as a first line therapy for ER+PR+ breast cancers. However, many patients acquire resistance to AI. In this study, we determined the response of antiprogestin CDB-4124 (Proellex) on the aromatase overexpressing and Letrozole resistant cell lines and also studies its mechanism of action in inhibition of breast cancer cell proliferation. For these studies we generated aromatase overexpressing T47D (T47Darom) and respective control (T47Dcon) breast cancer cell lines by stable transfection with plasmid containing CYP19A1 gene, or empty vector respectively. Letrozole resistant cell line (T47DaromLR) was generated by incubating T47Darom for 75 weeks in the presence of 10μM Letrozole. Cell proliferation was determined by MTT or crystal violet assays. Gene expressions were quantified by QRT-PCR whereas proteins were identified by western blot analyses, flow cytometry and immunofluorescence staining. Aromatase activity was determined by estradiol ELISA. The effects of Proellex on the anchorage independent growth were measured by soft agar colony formation. Statistical differences between the various groups were determined by Student's ‘t’ test or ANOVA followed by Bonferroni's post hoc test. Results showed that T47Darom and T47DaromLR cell lines had significantly higher aromatase expression (mRNA; 80–90 fold and protein) and as a result exhibited increased aromatization of testosterone to estradiol as compared to T47Dcon. Both these cell lines showed enhanced growth in the presence of Testosterone (50–60%). In T47DaromLR cells increased PR-B and EGFR expression as compared to T47Dcon cells was observed. Proellex and other known aromatase inhibitors (Letrozole, Anastrozole, and Exemestane) inhibited testosterone induced cell proliferation and anchorage independent growth of T47Darom cells. Cell growth inhibition was significantly greater when cells were treated with Proellex alone or in combination with other AIs as compared to AIs alone. Proellex inhibited mRNA and protein levels of PR-B, reduced PRB/p300 complex formation in the nuclei and significantly reduced EGFR expression in T47Darom cells. Our results in the present study indicate that antiproliferative effect of Proellex is probably due to PR-B/EGFR modulation in ER+PR+, aromatase expressing cells. Overall these results suggest that antiprogestin, Proellex can be developed as a possible treatment strategy for aromatase overexpressing ER+/PR+ breast cancer patients as well as for aromatase inhibitor resistant breast cancer patients.

P2-17-05: Antiprogestin Proellex Suppresses Proliferation of Aromatase Overexpressing and Letrozole Resistant T47D Breast Cancer Cells.

Abstract Background: Aromatase is a cytochrome P450 CYP19A1 enzyme responsible for the conversion of C19 androgens to C18 estrogen. Aromatase overexpression leads to increase in local estrogen concentration in post menopausal women diagnosed for breast cancer. Aromatase inhibitors (AI) are used as one of the first line therapies for the treatment of ER+PR+ breast cancers. However, many patients acquire resistance to AI treatment. Therefore alternative approaches are being sought for patients with AI resistance. Previous reports suggest that upregulation of progesterone receptor can lead to enhanced expression of EGFR/ERK/MAPK involved in acquiring resistance. In this study, we evaluated the effect of a selective progesterone receptor modulator, CDB4124 (Proellex) with low glucocorticoid activity on aromatase overexpressing and Letrozole resistant T47D cells. Methods: Aromatase overexpressing T47D (T47Darom) and respective control (T47Dcon) breast cancer cell lines were generated by stable transfection with plasmid containing CYP19A1 coding region, or empty vector respectively. Letrozole resistant cell line (T47DaromLR) was generated by incubating T47Darom for 75 weeks in the presence of 10μM Letrozole. Cell proliferation was determined by MTT or Crystal violet assays. Gene expressions were quantitated by qRT-PCR whereas proteins were identified by western blot analyses, flow cytometry and immunofluorescence staining. Aromatase activity was determined by estradiol ELISA. The effects of Proellex on anchorage independent growth were measured by soft agar colony formation. Statistical differences between the various groups were determined by Student's ‘T’ test or ANOVA followed by Bonferroni's post hoc test. Results: T47Darom and T47DaromLR cell lines had significantly higher aromatase expression (mRNA and protein) and as a result exhibited increased conversion of testosterone to estradiol as compared to T47Dcon. Both these cell lines showed enhanced growth in the presence of Testosterone. In T47Darom cells increased PR-B and EGFR expression as compared to T47Dcon cells was observed. Proellex, Letrozole and other known AI (Anastrozole, Exemestane) inhibited testosterone induced cell proliferation and anchorage independent growth of T47Darom cells. The inhibition of cell proliferation was significantly greater when cells were treated with Proellex in combination to other AIs. Proellex inhibited mRNA and protein levels of PR-B, reduced PRB/p300 complex formation in the nuclei and significantly reduced EGFR expression in T47Darom cells. Our results in the present study indicate that antiproliferative effect of Proellex may be due to PR-B/EGFR modulation in ER+PR+, aromatase overexpressing cells. Conclusion: Overall these results suggest that antiprogestin, Proellex could be developed as a possible treatment strategy for aromatase overexpressing ER+/PR+ breast cancer patients as well as for AI resistant breast cancer patients. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-17-05.

P01-441 - Ethnic variation in emotion regulation: do cultural differences end where psychopathology begins?

IntroductionEmotion regulation (ER) via cognitive reappraisal (CR) has been shown to be superior to the use of expressive suppression (ES) in terms of several aspects of mental well-being. However, a cultural perspective suggests that the consequences of ES may be moderated by cultural values (Western/individualistic vs. Eastern/collectivistic values).ObjectiveTo test this hypothesis that ES may be associated with better outcomes in collectivistic cultures (e.g. Turkey) than in individualistic cultures (e.g. Germany) not only in healthy individuals but also in patients with mental disorders.AimThis study aims to gather knowledge to what extent associations of ER strategies and mental health are universal or rather culturally specific.MethodsWe investigated healthy (n = 30) and depressed (n = 30) German women and healthy (n = 30) and depressed (n = 30) Turkish immigrants living in Germany. Groups were compared in terms of frequency of ER strategies (CR and ES) and their consequences for different aspects of mental well-being.ResultsHealthy Turkish immigrants exhibited a greater ER flexibility (frequent use of ES plus frequent use of CR) what was associated with more positive outcomes of ES in Turkish than in German women. None of these differences were found between patient samples, both of which showed a greater use of ES than CR.ConclusionsResults suggest that cultural moderation of ES consequences are associated with a greater ER flexibility in healthy Turkish individuals. Depressed Turkish patients may not profit from ES due to their more rigid use of ES.

The normative development of emotion regulation strategy use in children and adolescents: a 2‐year follow‐up study

Emotion regulation involves intrinsic and extrinsic processes responsible for managing one's emotions toward goal accomplishment. Research on emotion regulation has predominantly focused on early developmental periods and the majority of emotion regulation research examining the pre-adult years has lacked a comprehensive theoretical framework. The current study examined the use of two strategies of emotion regulation during childhood and adolescents, as conceptualised within Gross's (1998) process-oriented model. To determine the use, norms and development of the Expressive Suppression and Cognitive Reappraisal strategies, the Emotion Regulation Questionnaire for Children and Adolescents (ERQ-CA) was administered to 1,128 participants aged between 9 and 15 years. Three data collection phases, each one year apart, enabled investigation of developmental patterns in the use of the two strategies. As predicted, Suppression use was found to be lower for older participants compared to their younger peers, and over time participants reported less use of this strategy. Older participants also scored lower on Reappraisal but stability over time was found. Also as expected, males reported more Suppression use compared to females. By documenting the development and norms for Cognitive Reappraisal and Expressive Suppression in a community sample of children and adolescents, the current study makes a significant contribution to our understanding of these two ER strategies during these developmental periods.

&lt;b&gt;&lt;i&gt;What Happened to the Ancient Library of Alexandria?&lt;/i&gt;&lt;/b&gt; Eds. Mostafa El-Abbadi and Omnia M. Fathallah. Leiden: Brill, 2008. 260p. $129, cloth (ISBN 9789004165458). LC 2008-4209.

Book Reviews sets the stage for what follows. Feather takes as his point of departure the thesis that “[i]n the … context of the British book trade, there are many groups … whose history has been neglected, misrepre- sented or marginalized” (p. 2): the number of axes along which such groups may form is large, for marginalization can take place along geographical, linguistic, cultural, political, religious, or sexual lines—or, for that matt er, a combination of these. Argu- ing that, in resistance to the socially (and often legally) sanctioned arrangements of the mainstream book trade, members of the trade catering to minority groups developed their own networks of produc- tion and distribution, he presents a series of suggestive, but broad-brush, vignett es of how these oft en clandestine networks oper- ated in diff erent contexts from Elizabethan times into the twentieth century and issues a clarion call for further research in these oft en overlooked areas of English book history in the name of developing a more richly textured—and complete—history of the British book trade. All of the subsequent papers contribute, in one way or the other, to Feather’s program of foregrounding litt le-trodden byways of publishing history. Although they have been arranged by the editors to accord with the chronological order of the topic treated, they can also be organized into broad thematic clusters: for the sake of convenience, we adopt the latt er strategy here. No less than fi ve of the contributions deal with various aspects of the periodi- cal press, covering the whole range of the British Isles. Susannah Randall presents an impressive study of the “unoffi cial” (i.e., unlicensed) newspapers published in London during the politically volatile period from 1677 to 1685 and their pub- lishers: combining statistical analysis of newspaper production with biographi- Book Trade Connections from the Seven- teenth to the Twentieth Centuries. Eds. John Hinks and Catherine Armstrong. New Castle, Del.; London: Oak Knoll; The British Museum (Print Networks), 2008. 265p. $49.95 (ISBN 15845622930; 0712350640). LC 2008-17892. Ever since its inception a little over a decade ago, the Print Networks series has served as a venue for the proceedings of the annual Conference on the History of the British Book Trade. Insofar as the purpose of this conference is to explore all aspects of the book trade in England, with special emphasis on the provinces and its (former) colonies, past installments of this series have presented, under the cover of broadly construed themes (such as “diversity,” “continuity and change,” or “the human face of the book trade”), sets of papers notable not only for the luxuriant diversity of topics that they cover but also for the stimulating variety of methodological approaches that they represent. The volume under review—the ninth in the series and the third pub- lished under the care of the current team of editors—is no exception to this rule. Comprising twelve papers delivered at the 2005 conference held at the University of Birmingham, it takes as its theme the personal, social, political, economic, and cultural connections that bind together the various (groups of) persons—authors, printers, publishers, distributors, and members of the reading public—involved in the book trade. Such a theme off ers the possibility for an almost unending series of variations as to subjects of inquiry and method of analysis: the authors, whose numbers are drawn from the worlds of academia, librarianship, and publishing, have made good use of this spacious Spiel- raum to cover a broad range of topics from a number of scholarly perspectives. The initial essay, penned by John Feather, is programmatic in character and

Reply to Dosing of Divalproex Extended Release

Article AbstractBecause this piece does not have an abstract, we have provided for your benefit the first 3 sentences of the full text.Sir: Dr. Feifel's observational information on the effectiveness of a loading dose strategy for divalproex ER adds a pragmatic extension to our recent publication. The one caveat we would add is that dosing practices that may be well tolerated in acutely manic, hospitalized patients may be less well tolerated in less severely ill outpatients, likely consequent to lower levels of increased activation.†‹†‹The article discussed here was supported by Abbott.†‹

Breast 18

Aims: The presence of cerbB-2 oncoprotein is said to predict failure to respond to endocrine therapy in breast cancer (particularly tamoxifen). The aim of the study was to determine whether the effect of oestrogen deprivation (by stopping HRT) on breast cancer is related to cerbB-2 oncoprotein expression. Methods and study: We identified 129 women who were on HRT at the time of diagnosis of breast cancer by core biopsy. Out of 129 women, 114 stopped HRT and 15 continued HRT till surgery. Ki67 (a marker of cell proliferation), progesterone receptor (PR), ER (oestrogen receptor) and cyclin D1 (a cell cycle inducer) were measured by immunohistochemistry on paired sections of core biopsy and operative specimens. CerbB-2 was measured on the operative specimen and was scored from 0 to 3. Results: Stopping HRT led to a significant fall in epithelial proliferation compared to continued group (P = 0.05), more so in ER positives (P = 0.045)* Mann–Whitney test. PR (P = 0.007)* and cyclin D1 (P = 0.05)* decreased significantly in responding tumours regardless of cerbB-2 status (P = 0.498, Kruskal–Wallis test). Conclusion: CerbB-2 expression does not prevent fall in cell proliferation due to HRT withdrawal. Aromatase inhibitors may still be the optimal strategy for ER and cerbB-2-positive breast cancers.

External Relationship Management: Health Care Implications and Future Digital Desirability

The Year 2000 problem can be broadly divided into internal and external activities. For many businesses, internal activities have received the majority of time and attention. Given the complex and interdependent nature of Aetna’s business relationships, management of its external relationships (ER’s) has proven to be a key success factor in taming its Y2K problem. As a service-based business for more than 150 years, Aetna is a quintessential example of what many today would describe as a “value web”—an organization that thrives on its ability to rapidly deliver services within a highly interdependent set of relationships. In this paper, Aetna’s Y2K ER management strategy and its evolution from A.T. Kearney’s Y2K risk mitigation model are discussed. Reviewed in detail are Aetna’s business landscape and an aggregate ER risk-rating approach. Aetna’s medical provider network is used to exemplify its ER management strategy. As a result of Aetna’s ER strategy, a new dynamic for the health care industry centered on contingency payment plans is highlighted. Looking forward, the concept of “digital desirability” and the applicability of Aetna’s ER strategy in the digital era is explored.