Bone fragility related to breast cancer treatment: The pivotal role of nurses in bone health program development, implementation, and testing.

Breast cancer treatment can affect estrogen levels leading to significant bone loss, osteoporosis, and risks for fracture. Although bone care guidelines are published, bone health interventions are often not routinely offered to at-risk individuals. This paper reports on the process of developing and implementing a nurse-led bilingual Breast and Bone Health Program (BBHP) in-person and online at a cancer centre in Montreal, Quebec (www.breastandbonehealth.ca, www.santeseinsetos.ca). The BBHP offers tailored bone health interventions (e.g., risk screening, information, rehabilitation, exercise prescriptions, nutritional counselling, and support for a health-promoting lifestyle). Over a two-year period, women treated for breast cancer (N = 430) took part in the program. Forty percent of surveyed participants (n = 97) initally reported being unaware that some breast cancer treatment could significantly affect bone health. Following the initial informational session with the BBHP nurse, self-reported bone health knowledge significantly increased, with 96% reporting sufficient information to manage their bone health. The BBHP offers both online and in-person risk assessment and bone health promotion activities and tools to both health care professionals and women with breast cancer. Herein, we review the background, BBHP development and implementation as well as preliminary program evaluation.

E-health tools in oncology nursing: Perceptions of nurses and contributions to patient care and advanced practice.

As oncology nurses confront a rapidly evolving field with increased workplace pressure, the integration of evidence-based connected health platforms within practice presents promise. This study explores nurses' perceptions regarding the utility of e-health tools, with a focus on the Oncology Interactive Navigator (OINTM), as a potential contributor to their practice and interactions with patients. Focus groups with oncology nurses were conducted at two time points: prior to exposure to the OINTM (T1, n=8) and four weeks post unrestricted tool access (T2, n=7). Using qualitative constant comparison analysis, three themes emerged: (1) Key factors driving e-health use are multidimensional and evolving; (2) Dual role of e-health in meeting patient needs and supporting practice; (3) E-health as a catalyst for professional development and networking. E-health is appealing to oncology nurses, as it serves to advance practice and support patient care. Future research should explore best practices for optimal clinical implementation among all stakeholders involved.

Bcl-2-modifying factor induces renal proximal tubular cell apoptosis in diabetic mice.

This study investigated the mechanisms underlying tubular apoptosis in diabetes by identifying proapoptotic genes that are differentially upregulated by reactive oxygen species in renal proximal tubular cells (RPTCs) in models of diabetes. Total RNAs isolated from renal proximal tubules (RPTs) of 20-week-old heterozygous db/m+, db/db, and db/db catalase (CAT)-transgenic (Tg) mice were used for DNA chip microarray analysis. Real-time quantitative PCR assays, immunohistochemistry, and mice rendered diabetic with streptozotocin were used to validate the proapoptotic gene expression in RPTs. Cultured rat RPTCs were used to confirm the apoptotic activity and regulation of proapoptotic gene expression. Additionally, studies in kidney tissues from patients with and without diabetes were used to confirm enhanced proapoptotic gene expression in RPTs. Bcl-2-modifying factor (Bmf) was differentially upregulated (P<0.01) in RPTs of db/db mice compared with db/m+ and db/db CAT-Tg mice and in RPTs of streptozotocin-induced diabetic mice in which insulin reversed this finding. In vitro, Bmf cDNA overexpression in rat RPTCs coimmunoprecipated with Bcl-2, enhanced caspase-3 activity, and promoted apoptosis. High glucose (25 mmol/L) induced Bmf mRNA expression in RPTCs, whereas rotenone, catalase, diphenylene iodinium, and apocynin decreased it. Knockdown of Bmf with small interfering RNA reduced high glucose-induced apoptosis in RPTCs. More important, enhanced Bmf expression was detected in RPTs of kidneys from patients with diabetes. These data demonstrate differential upregulation of Bmf in diabetic RPTs and suggest a potential role for Bmf in regulating RPTC apoptosis and tubular atrophy in diabetes.

Naked1 antagonizes Wnt signaling by preventing nuclear accumulation of ß-catenin.

Cyto-nuclear shuttling of ß-catenin is at the epicenter of the canonical Wnt pathway and mutations in genes that result in excessive nuclear accumulation of ß-catenin are the driving force behind the initiation of many cancers. Recently, Naked Cuticle homolog 1 (Nkd1) has been identified as a Wnt-induced intracellular negative regulator of canonical Wnt signaling. The current model suggests that Nkd1 acts between Disheveled (Dvl) and ß-catenin. Here, we employ the zebrafish embryo to characterize the cellular and biochemical role of Nkd1 in vivo. We demonstrate that Nkd1 binds to ß-catenin and prevents its nuclear accumulation. We also show that this interaction is conserved in mammalian cultured cells. Further, we demonstrate that Nkd1 function is dependent on its interaction with the cell membrane. Given the conserved nature of Nkd1, our results shed light on the negative feedback regulation of Wnt signaling through the Nkd1-mediated negative control of nuclear accumulation of ß-catenin.

Catalase overexpression prevents hypertension and tubular apoptosis in angiotensinogen transgenic mice.

Transgenic mice that overexpress angiotensinogen, the sole precursor of angiotensins, in their renal proximal tubular cells develop hypertension, albuminuria, and tubular apoptosis. These pathological changes are due to enhanced generation of reactive oxygen species in the proximal tubule cells. Here, we determined whether overexpression of catalase to decrease oxidant injury in the proximal tubular cells could reverse these abnormalities. Double-transgenic mice specifically overexpressing angiotensinogen and catalase in their renal proximal tubular cells were created by cross-breeding the single transgenics. Non-transgenic littermates served as controls. Overexpression of catalase prevented hypertension, albuminuria, tubulointerstitial fibrosis, and tubular apoptosis in the angiotensinogen transgenic mice. Furthermore, the double transgenics had lower reactive oxygen species generation and reduced pro-fibrotic and apoptotic gene expression in the renal proximal tubular cells. Renal angiotensin converting enzyme-2 expression and urinary angiotensin 1-7 levels were downregulated in the single but normal in the double-transgenic mice. Thus, we suggest that the intrarenal renin-angiotensin system and reactive oxygen species generation have an important role in the development of hypertension and renal injury.

Application of an integrated physical and functional screening approach to identify inhibitors of the Wnt pathway.

Large-scale proteomic approaches have been used to study signaling pathways. However, identification of biologically relevant hits from a single screen remains challenging due to limitations inherent in each individual approach. To overcome these limitations, we implemented an integrated, multi-dimensional approach and used it to identify Wnt pathway modulators. The LUMIER protein-protein interaction mapping method was used in conjunction with two functional screens that examined the effect of overexpression and siRNA-mediated gene knockdown on Wnt signaling. Meta-analysis of the three data sets yielded a combined pathway score (CPS) for each tested component, a value reflecting the likelihood that an individual protein is a Wnt pathway regulator. We characterized the role of two proteins with high CPSs, Ube2m and Nkd1. We show that Ube2m interacts with and modulates beta-catenin stability, and that the antagonistic effect of Nkd1 on Wnt signaling requires interaction with Axin, itself a negative pathway regulator. Thus, integrated physical and functional mapping in mammalian cells can identify signaling components with high confidence and provides unanticipated insights into pathway regulators.