Endocrine therapy: defining the path of least resistance

One of the best-characterized oncogenic mechanisms in breast cancer is the aberrant activation of phosphatidylinositol-3-kinase, protein kinase B, and mammalian target of rapamycin signaling. In both endocrine-resistant disease and breast cancer stem cells, this is commonly caused by specific genetic lesions or amplification of key pathway components or both. These observations have generated two interesting hypotheses. Firstly, do these genetic anomalies provide clinically significant biomarkers predictive of endocrine resistance? Secondly, do tamoxifen-resistant breast cancer cells emerge from a stem-like cell population? New studies, published in Breast Cancer Research, raise the possibility that these hypotheses are intrinsically linked

Annual Survey of Virginia Law: Business and Corporate Law

This article reviews recent developments in the law affecting Virginia businesses and corporations. Part II discusses recent judicial decisions, including: two Fourth Circuit Court of Appeals opinions, one interpreting and upholding the constitutionality of the Virginia statutes regulating hostile takeovers, and the other determining the owner of partnership property upon dissolution of the partnership; two Supreme Court of Virginia decisions regarding non-stock corporations, one determining the validity of the board of directors, and one deciding whether the Property Owners\u27 Association Act supersedes the bylaws of an incorporated non-stock property owners\u27 association; four Supreme Court of Virginia decisions including one denying a shareholder\u27s request for a list of shareholders, one refusing to pierce the corporate veil, another refusing to dissolve a closely held corporation held by a husband and a wife going through divorce, and finally, one determining when a limited partner can be held liable for debts of the partnership. Part III discusses several acts of the 1996 session of the Virginia General Assembly amending Virginia\u27s corporation, partnership, and limited liability company statutes

Targeting cyclin-dependent kinase 1 (CDK1) but not CDK4/6 or CDK2 is selectively lethal to MYC-dependent human breast cancer cells

Background Although MYC is an attractive therapeutic target for breast cancer treatment, it has proven challenging to inhibit MYC directly, and clinically effective pharmaceutical agents targeting MYC are not yet available. An alternative approach is to identify genes that are synthetically lethal in MYC-dependent cancer. Recent studies have identified several cell cycle kinases as MYC synthetic-lethal genes. We therefore investigated the therapeutic potential of specific cyclin-dependent kinase (CDK) inhibition in MYC-driven breast cancer. Methods Using small interfering RNA (siRNA), MYC expression was depleted in 26 human breast cancer cell lines and cell proliferation evaluated by BrdU incorporation. MYC-dependent and MYC-independent cell lines were classified based on their sensitivity to siRNA-mediated MYC knockdown. We then inhibited CDKs including CDK4/6, CDK2 and CDK1 individually using either RNAi or small molecule inhibitors, and compared sensitivity to CDK inhibition with MYC dependence in breast cancer cells. Results Breast cancer cells displayed a wide range of sensitivity to siRNA-mediated MYC knockdown. The sensitivity was correlated with MYC protein expression and MYC phosphorylation level. Sensitivity to siRNA-mediated MYC knockdown did not parallel sensitivity to the CDK4/6 inhibitor PD0332991; instead MYC-independent cell lines were generally sensitive to PD0332991. Cell cycle arrest induced by MYC knockdown was accompanied by a decrease in CDK2 activity, but inactivation of CDK2 did not selectively affect the viability of MYC-dependent breast cancer cells. In contrast, CDK1 inactivation significantly induced apoptosis and reduced viability of MYC-dependent cells but not MYC- independent cells. This selective induction of apoptosis by CDK1 inhibitors was associated with up-regulation of the pro-apoptotic molecule BIM and was p53-independent. Conclusions Overall, these results suggest that further investigation of CDK1 inhibition as a potential therapy for MYC-dependent breast cancer is warranted.</p

The problem of unknown parameters in neutron resonance theory

In this thesis, three problems concerned with the estimation of unknown resonance parameters in slow neutron spectroscopy are treated, fhe average level spacing \u3c D \u3e as a function of nuclear excitation energy E can he calculated by considering the nucleus as a gas of free fermions and then including corrections for the interactions present in actual nuclei. In Chapter II, the correction parameters used for this purpose by Gilbert and Cameron (1965) are readjusted so that excellent agreement with the observed level spacings is obtained. This work, described in section lie is the original work of the candidate and has been previously published (Cook, Ferguson and Musgrove 1967). The improved parameters codify all experimental masses as well as level spacings. Chapter III deals with the problem of inferring the thermal neutron cross section when no information is available about the nucleus in question. The original contribution of the candidate in sections Illb-e has been previously published (Musgrove 1968a). Statistical methods were used to obtain the mean and variance of thermal cross sections on the basis of a uniform sequence of levels and on a more exact model where the distribution of level spacings and reduced neutron widths are taken into account

Distinct and redundant functions of cyclin E1 and cyclin E2 in development and cancer

The highly conserved E-type cyclins are core components of the cell cycle machinery, facilitating the transition into S phase through activation of the cyclin dependent kinases, and assembly of pre-replication complexes on DNA. Cyclin E1 and cyclin E2 are assumed to be functionally redundant, as cyclin E1-/- E2-/- mice are embryonic lethal while cyclin E1-/- and E2-/- single knockout mice have primarily normal phenotypes. However more detailed studies of the functions and regulation of the E-cyclins have unveiled potential additional roles for these proteins, such as in endoreplication and meiosis, which are more closely associated with either cyclin E1 or cyclin E2. Moreover, expression of each E-cyclin can be independently regulated by distinct transcription factors and microRNAs, allowing for context-specific expression. Furthermore, cyclins E1 and E2 are frequently expressed independently of one another in human cancer, with unique associations to signatures of poor prognosis. These data imply an absence of co-regulation of cyclins E1 and E2 during tumorigenesis and possibly different contributions to cancer progression. This is supported by in vitro data identifying divergent regulation of the two genes, as well as potentially different roles in vivo

Perceptions of Nurses Who Are Second Victims in a Hospital Setting

https://scholarlycommons.henryford.com/nursresconf2021/1004/thumbnail.jp

Rose Marie Waltz

Illustration of roses and vines in border around various titleshttps://scholarsjunction.msstate.edu/cht-sheet-music/12490/thumbnail.jp

Crafting Partnerships: Exploring Student-Led Feminist Strategies for Community Literacy Projects

Relationships have served as a cornerstone to feminist research in community-based research and service learning sites, as feminist scholars have argued for co-constructing knowledges in these sites, while being attentive to the reciprocal nature of these relationships within any context of and for learning (Bayer, Grossman, & Dubois, 2015; Parks & Goldblatt, 2000; Novek, 1999). These relationships are especially crucial when feminists attempt to create real and sustained partnerships through mentoring in their community-based literacy site (DuBois & Karcher, 2005). We stress the value of cultivating sustained relationships, as oftentimes discourses surrounding service learning exhibit a level of engagement that is not sustained and/or does not adequately expose the workings of power and privilege in a systematic way (Deans, 2002). In light of our feminist motivations, we need to continuously create spaces to foreground the value of experience and take seriously the process of cultivating relationships with students in ways that are both ethical and accountable.https://nsuworks.nova.edu/shss_facbooks/1122/thumbnail.jp