3,3′-Diindolylmethane and paclitaxel act synergistically to promote apoptosis in HER2/neu human breast cancer cells

Background. HER2/neu positive breast tumors are difficult to treat. About 25 to 30% of invasive breast tumors overexpress the HER2/neu oncogene. These tumors are aggressive and become resistant to chemotherapeutic drugs. 3,3′-diindolylmethane (DIM), the active metabolite of indole-3-carbinol, a naturally occurring compound found in cruciferous vegetables, has been found to have anti-cancer properties in both humans and animals. DIM has been shown to induce cell cycle arrest and apoptosis in animal breast cancer models. Because HER2/neu overexpression confers resistance to paclitaxel, and DIM has anti-tumor effects, we hypothesized that DIM will enhance the cytotoxic effects of paclitaxel, a common taxane drug, on human Her2/neu breast cancer cells by potentiating its effect on cell cycle and stimulating apoptosis. Methods. The MDA-MB-435eB1 human Her2/neu breast cancer cells were treated with varying concentrations of DIM and paclitaxel. The cells were analyzed at different time points (24, 48, and 72 h). Proliferation was measured by a commercial cell proliferation assay (Promega Procheck Assay). Cell-cycle analysis and apoptosis were determined by flow cytometry. Western blot analysis was performed on to determine the effect of DIM and/or paclitaxel on the proteins involved in apoptosis, and epidermal growth factor-induced activation of HER2/neu and ERK1/2 signaling proteins. Results. Both DIM and paclitaxel exhibited time and concentration dependent inhibition of cell proliferation. TUNEL assay indicated that the combination also increased the number of apoptotic cells more than either agent alone. The presence of cleaved poly (ADPRibose) polymerase (PARP) significantly increased in the combination treatment, whereas Bcl-2 is decreased. DIM alone decreased the activation of the Her2/neu receptor; the combination decreased the activation of ERK1/ERK2. Conclusions. DIM in combination with paclitaxel synergistically inhibits growth of Her2/neu human breast cancer cells through G2M phase cell-cycle arrest and induction of apoptosis/necrosis. The Her2/neu receptor and its downstream signaling protein ERK1/2 appear to be involved in DIM’s affect on cell growth and differentiation, whereas apoptosis appears to be mediated through the mitochondrial pathway (Bcl-2/ PARP). It appears DIM, a naturally occurring, nontoxic compound, may be a beneficial addition to a traditional (taxane-based) chemotherapy regimen

Forensic Social Work: Practice and Vision

Forensic social work can bridge the gap between the criminal justice and mental health systems and serve clients who “fall between the cracks.” The authors describe theoretical and clinical issues, utilizing case examples and the literature to develop a conceptual paradigm for the role of social workers in this area

Searching for Birth Parents: Motive and Experiences of a Selected Sample of Adult Adoptees

This study documented the experiences adoptees encounter while searching for their birth parents, and how they were effected by searching. The study also assessed the adoptees support for reviewing laws governing adoption records. Twenty-six adult adoptees were interviewed, their responses recorded and analyzed. Adoptees reported learning of their adoption at an early age. Overall adoptees did not have negative feelings about being adopted and reported positive relationships with their adoptive parents. Adoptees reported a variety of reasons for searching for their birth parents and experienced a number of difficulties while searching. Some of the difficulties were: long distances, legal boundaries, and lack of knowledge about how to search. Despite the many difficulties, adoptees saw searching as a positive experience. Adoptees recommend that other adoptees who are considering a search have a strong personal support system throughout the search. Although the adoptees in this study indicated the laws on adoption records need to be changed, a review of literature does not support a change. The available research indicated that a very small portion of the adopted population searches for their birth parents. However, the accuracy of the research may be questioned because it is difficult to accurately determine the number of adoptees who choose to search for their birth parents

3,3\u27-Diindolylmethane enhances apoptosis in docetaxel-treated breast cancer cells by generation of reactive oxygen species.

CONTEXT: A major problem in the treatment of cancer is the development of toxic side effects and resistance to chemotherapy. The use of plant compounds to overcome resistance and prevent toxicity is a potential strategy for treatment. OBJECTIVE: We evaluated whether 3,3\u27-diindolylmethane (DIM) enhanced the sensitivity of breast cancer cells to docetaxel (DOC). MATERIALS AND METHODS: MDA-MB231 and Sk-BR-3 cells were treated with and without 25 or 50 µM of DIM and 1 nM of DOC for 48 and 72 h, respectively. MTT assay was used to measure cell survival. Apoptosis and intracellular reactive oxygen species (ROS) were determined by flow cytometry. The expression of proteins regulating ROS production and apoptosis was evaluated by immunoblotting technique. RESULTS: Combining 25 µM of DIM with 1 nM DOC decreased cell survival by 42% in MDA-MB231 cells and 59% in Sk-BR-3 cells compared to control, DIM, or DOC (p ≤ 0.05). The combination treatment increased apoptosis over 20% (p ≤ 0.01) in both cell lines, which was associated with decreased Bcl-2, increased Bax, cleaved PARP and activated JNK (p ≤ 0.01). ROS production increased by 46.5% in the MDA-MB231 and 29.3% in Sk-BR-3 cells with the combination compared to DIM or DOC alone. Pretreating cells with N-acetyl-cysteine or Tiron abrogated the anti-survival effect of the combination. The increase in ROS was associated with a 54% decrease in MnSOD and 47% increase in NOX2 protein compared to the other groups. CONCLUSIONS: Our findings indicated that DIM enhances the sensitivity of breast cancer cells to DOC treatment by increasing ROS, which led to decreased cell survival and apoptosis

Reclaiming heritage: colourization, culture wars and the politics of nostalgia

This article considers the discursive continuities between a specifically liberal defence of cultural patrimony, evident in the debate over film colourization, and the culture war critique associated with neo-conservatism. It examines how a rhetoric of nostalgia, linked to particular ideas of authenticity,canonicity and tradition,has been mobilized by the right and the left in attempts to stabilize the confguration and perceived transmission of American cultural identity. While different in scale, colourization and multiculturalism were seen to create respective (postmodern) barbarisms against which defenders of culture, heritage and good taste could unite. I argue that in its defence of the ‘classic’ work of art, together with principles of aesthetic distinction and the value of cultural inheritance,the anti-colourization lobby helped enrich and legitimize a discourse of tradition that, at the end of the 1980s, was beginning to reverberate powerfully in the conservative challenge to a ‘crisis’ within higher education and the humanities. This article attempts to complicate the contemporary politics of nostalgia, showing how a defence of cultural patrimony has distinguished major and minor culture wars, engaging left and right quite differently but with similar presuppositions

Human mucosal associated invariant T cells detect bacterially infected cells

Control of infection with Mycobacterium tuberculosis (Mtb) requires Th1-type immunity, of which CD8+ T cells play a unique role. High frequency Mtb-reactive CD8+ T cells are present in both Mtb-infected and uninfected humans. We show by limiting dilution analysis that nonclassically restricted CD8+ T cells are universally present, but predominate in Mtbuninfected individuals. Interestingly, these Mtb-reactive cells expressed the Va7.2 T-cell receptor (TCR), were restricted by the nonclassical MHC (HLA-Ib) molecule MR1, and were activated in a transporter associated with antigen processing and presentation (TAP) independent manner. These properties are all characteristics of mucosal associated invariant T cells (MAIT), an "innate" T-cell population of previously unknown function. These MAIT cells also detect cells infected with other bacteria. Direct ex vivo analysis demonstrates that Mtb-reactive MAIT cells are decreased in peripheral blood mononuclear cells (PBMCs) from individuals with active tuberculosis, are enriched in human lung, and respond to Mtb-infected MR1-expressing lung epithelial cells. Overall, these findings suggest a generalized role for MAIT cells in the detection of bacterially infected cells, and potentially in the control of bacterial infection. © 2010 Gold et al

A prospective investigation of dietary patterns and internalizing and externalizing mental health problems in adolescents

© 2016 The Authors. Food Science & Nutrition published by Wiley Periodicals, Inc.Investigating protective and risk factors that influence mental health in young people is a high priority. While previous cross-sectional studies have reported associations between diet and mental health among adolescents, few prospective studies exist. The aim of this study was to examine prospective relationships between dietary patterns and mental health among adolescents participating in the Western Australian Pregnancy Cohort (Raine) Study. Self-report questionnaires were used to assess indicators of mental health (Youth Self-Report externalizing/internalizing T-scores) and Western and Healthy dietary patterns (identified using factor analysis) at 14 (2003–2005) and 17 years (2006–2008). Multivariate linear and logistic regression were used to assess relationships between dietary patterns and mental health. Complete data were available for 746 adolescents. In females only, the Western dietary pattern z–score at 14 years was positively associated with greater externalizing behaviors at 17 years (ß = 1.91; 95% CI: 0.04, 3.78) and a greater odds of having clinically concerning externalizing behaviors at 17 years (OR = 1.90; 95% CI: 1.06, 3.41). No other statistically significant associations were observed. Overall our findings only lend partial support to a link between diet and mental health. We found it to be specific to females consuming a Western dietary pattern and to externalizing behaviors. Future research on dietary patterns and mental health needs to consider possible sex differences and distinguish between different mental health outcomes as well as between healthy and unhealthy dietary patterns

Freiraumwende: Vom Freiraum her denken, planen und handeln

Freiraumsicherung und -entwicklung erfährt als ein grundlegendes Zukunftsthema große Resonanz in Wissenschaft, Planungspraxis und Politik. Zentrales Anliegen der Raumwissenschaften und der Planungspraxis ist es, Freiraumsicherung und -entwicklung deutlich stärker als eigenständige Aufgabe der Raumentwicklung (räumlichen Gesamtplanung) zu etablieren. Hierfür ist ein empirisch fundierter, strategisch vorsorgender und überfachlich koordinierter Freiraumschutz mit hoher politischer Gewichtung und rechtlicher Verbindlichkeit notwendig, denn Impulse für die Raumentwicklung gehen noch immer in erster Linie von freiraumbeanspruchenden Flächenforderungen für die Siedlungs- und Infrastrukturentwicklung aus. Das Positionspapier nennt zentrale Thesen und Forderungen, die einen grundlegenden Perspektivenwechsel in der räumlichen Planung forcieren. Ziel muss es sein, "vom Freiraum her zu denken, zu planen und zu handeln" und damit den Freiraum innerhalb und außerhalb von Siedlungsgebieten als eigenständige Raumkategorie stärker hervorzuheben, ihn neu einzuordnen und zu bewerten. In diesem Sinne wird eine "Freiraumwende" auf allen Ebenen der räumlichen Planung gefordert.The preservation and development of open spaces is a fundamental subject for future research, planning practice and politics. The key objective of spatial science and planning practice is to establish the protection and development of open spaces much more strongly as an independent task of spatial development ("overall spatial planning"). This requires empirically based, strategically preventive and interdisciplinary coordinated protection of open space with a high political weighting and legally binding nature, as the driving force for spatial development still comes primarily from land demands for settlement and infrastructure development requiring open space. The position paper sets out key theses and demands that call for a fundamental change of perspective in spatial planning. The aim must be to "think, plan and act from the perspective of open space" and to emphasize open space inside and outside settlement areas more strongly as an independent spatial category, to categorize and value it anew. In this sense, an "open space turnaround" is required at all levels of spatial planning

Low dietary intake of magnesium is associated with increased externalising behaviours in adolescents

Objective: Adequate Zn and Mg intakes may be beneficial for the prevention and treatment of mental health problems, such as depression, anxiety and attention-deficit hyperactivity disorder. We aimed to investigate the prospective association between dietary intakes of Zn and Mg and internalising and externalising behaviour problems in a population-based cohort of adolescents. Design: Prospective analysis (general linear mixed models) of dietary intakes of Zn and Mg assessed using a validated FFQ and mental health symptoms assessed using the Youth Self-Report (YSR), adjusting for sex, physical activity, family income, supplement status, dietary misreporting, BMI, family functioning and energy intake. Setting: Western Australian Pregnancy Cohort (Raine) Study. Subjects: Adolescents (n 684) at the 14- and 17-year follow-ups. Results: Higher dietary intake of Mg (per SD increase) was significantly associated with reduced externalising behaviours (β=−1·45; 95 % CI −2·40, −0·50; P=0·003). There was a trend towards reduced externalising behaviours with higher Zn intake (per SD increase; β=−0·73; 95 % CI −1·57, 0·10; P=0·085).Randomised controlled trials are necessary to determine any benefit of micronutrient supplementation in the prevention and treatment of mental health problems in adolescents.The study shows an association between higher dietary Mg intake and reduced externalising behaviour problems in adolescents. We observed a similar trend, although not statistically significant, for Zn intake. Randomised controlled trials are necessary to determine any benefit of micronutrient supplementation in the prevention and treatment of mental health problems in adolescents