Publications by authors named "Barbara Parker"

152 Publications

Geographical Mapping in a School District Leverages the Power of Students' Health Data and Services.

J Sch Health 2021 Nov 23. Epub 2021 Nov 23.

Oakland Unified School District, 1000 Broadway Suite 150, Oakland, CA, 94607.

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http://dx.doi.org/10.1111/josh.13109DOI Listing
November 2021

Assessment of Residual Cancer Burden and Event-Free Survival in Neoadjuvant Treatment for High-risk Breast Cancer: An Analysis of Data From the I-SPY2 Randomized Clinical Trial.

JAMA Oncol 2021 Nov;7(11):1654-1663

Medical Oncology, Swedish Cancer Institute, Seattle, Washington.

Importance: Residual cancer burden (RCB) distributions may improve the interpretation of efficacy in neoadjuvant breast cancer trials.

Objective: To compare RCB distributions between randomized control and investigational treatments within subtypes of breast cancer and explore the relationship with survival.

Design, Setting, And Participants: The I-SPY2 is a multicenter, platform adaptive, randomized clinical trial in the US that compares, by subtype, investigational agents in combination with chemotherapy vs chemotherapy alone in adult women with stage 2/3 breast cancer at high risk of early recurrence. Investigational treatments graduated in a prespecified subtype if there was 85% or greater predicted probability of higher rate of pathologic complete response (pCR) in a confirmatory, 300-patient, 1:1 randomized, neoadjuvant trial in that subtype. Evaluation of a secondary end point was reported from the 10 investigational agents tested in the I-SPY2 trial from March 200 through 2016, and analyzed as of September 9, 2020. The analysis plan included modeling of RCB within subtypes defined by hormone receptor (HR) and ERBB2 status and compared control treatments with investigational treatments that graduated and those that did not graduate.

Interventions: Neoadjuvant paclitaxel plus/minus 1 of several investigational agents for 12 weeks, then 12 weeks of cyclophosphamide/doxorubicin chemotherapy followed by surgery.

Main Outcomes And Measures: Residual cancer burden (pathological measure of residual disease) and event-free survival (EFS).

Results: A total of 938 women (mean [SD] age, 49 [11] years; 66 [7%] Asian, 103 [11%] Black, and 750 [80%] White individuals) from the first 10 investigational agents were included, with a median follow-up of 52 months (IQR, 29 months). Event-free survival worsened significantly per unit of RCB in every subtype of breast cancer (HR-positive/ERBB2-negative: hazard ratio [HZR], 1.75; 95% CI, 1.45-2.16; HR-positive/ERBB2-positive: HZR, 1.55; 95% CI, 1.18-2.05; HR-negative/ERBB2-positive: HZR, 2.39; 95% CI, 1.64-3.49; HR-negative/ERBB2-negative: HZR, 1.99; 95% CI, 1.71-2.31). Prognostic information from RCB was similar from treatments that graduated (HZR, 2.00; 95% CI, 1.57-2.55; 254 [27%]), did not graduate (HZR, 1.87; 95% CI, 1.61-2.17; 486 [52%]), or were control (HZR, 1.79; 95% CI, 1.42-2.26; 198 [21%]). Investigational treatments significantly lowered RCB in HR-negative/ERBB2-negative (graduated and nongraduated treatments) and ERBB2-positive subtypes (graduated treatments), with improved EFS (HZR, 0.61; 95% CI, 0.41-0.93) in the exploratory analysis.

Conclusions And Relevance: In this randomized clinical trial, the prognostic significance of RCB was consistent regardless of subtype and treatment. Effective neoadjuvant treatments shifted the distribution of RCB in addition to increasing pCR rate and appeared to improve EFS. Using a standardized quantitative method to measure response advances the interpretation of efficacy.

Trial Registration: ClinicalTrials.gov Identifier: NCT01042379.
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http://dx.doi.org/10.1001/jamaoncol.2021.3690DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8446908PMC
November 2021

Correction: Maning et al. Antagonistic Roles of GRK2 and GRK5 in Cardiac Aldosterone Signaling Reveal GRK5-Mediated Cardioprotection via Mineralocorticoid Receptor Inhibition. 2020, , 2868.

Int J Mol Sci 2021 Jul 21;22(15). Epub 2021 Jul 21.

Laboratory for the Study of Neurohormonal Control of the Circulation, Department of Pharmaceutical Sciences, College of Pharmacy, Nova Southeastern University, Fort Lauderdale, FL 33328, USA.

The authors wish to make the following correction to this paper [...].
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http://dx.doi.org/10.3390/ijms22157767DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8346130PMC
July 2021

Elevated risk thresholds predict endocrine risk-reducing medication use in the Athena screening registry.

NPJ Breast Cancer 2021 Aug 3;7(1):102. Epub 2021 Aug 3.

University of California, San Francisco, San Francisco, CA, USA.

Risk-reducing endocrine therapy use, though the benefit is validated, is extremely low. The FDA has approved tamoxifen and raloxifene for a 5-year Breast Cancer Risk Assessment Tool (BCRAT) risk ≥ 1.67%. We examined the threshold at which high-risk women are likely to be using endocrine risk-reducing therapies among Athena Breast Health Network participants from 2011-2018. We identified high-risk women by a 5-year BCRAT risk ≥ 1.67% and those in the top 10% and 2.5% risk thresholds by age. We estimated the odds ratio (OR) of current medication use based on these thresholds using logistic regression. One thousand two hundred and one (1.2%) of 104,223 total participants used medication. Of the 33,082 participants with 5-year BCRAT risk ≥ 1.67%, 772 (2.3%) used medication. Of 2445 in the top 2.5% threshold, 209 (8.6%) used medication. Participants whose 5-year risk exceeded 1.67% were more likely to use medication than those whose risk was below this threshold, OR 3.94 (95% CI = 3.50-4.43). The top 2.5% was most strongly associated with medication usage, OR 9.50 (8.13-11.09) compared to the bottom 97.5%. Women exceeding a 5-year BCRAT ≥ 1.67% had modest medication use. We demonstrate that women in the top 2.5% have higher odds of medication use than those in the bottom 97.5% and compared to a risk of 1.67%. The top 2.5% threshold would more effectively target medication use and is being tested prospectively in a randomized control clinical trial.
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http://dx.doi.org/10.1038/s41523-021-00306-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8333106PMC
August 2021

Calcium Alkali Syndrome Treated With Hemodialysis.

Authors:
Barbara M Parker

Cureus 2021 Mar 7;13(3):e13749. Epub 2021 Mar 7.

Clinical Pharmacy, AdventHealth Orlando, Orlando, USA.

Malignancy, primary hyperparathyroidism, and vitamin D intoxication are the most common causes of hypercalcemia. Symptoms of hypercalcemia are nonspecific and require a plasma calcium level to diagnose. Undiagnosed hypercalcemia can cause renal failure long-term. Here, we describe a unique case of hypercalcemia resulting in acute kidney injury (AKI) secondary to overconsumption of calcium carbonate (Tums).
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http://dx.doi.org/10.7759/cureus.13749DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8022897PMC
March 2021

KRAS-Mutated, Estrogen Receptor-Positive Low-Grade Serous Ovarian Cancer: Unraveling an Exceptional Response Mystery.

Oncologist 2021 04 2;26(4):e530-e536. Epub 2021 Mar 2.

Center for Personalized Cancer Therapy and Moores Cancer Center, University of California San Diego, La Jolla, California, USA.

We report on a woman with aggressive estrogen receptor-positive, KRAS-mutated ovarian cancer who achieved a remarkable response to combination therapy with the MEK inhibitor (trametinib) and the aromatase inhibitor (letrozole), even though the disease had failed to respond to a combination of a PI3K inhibitor and different MEK inhibitor, as well as to trametinib and the estrogen modulator, tamoxifen, and to letrozole by itself. The mechanism of action for exceptional response was elucidated by in vitro experiments that demonstrated that the fact that tamoxifen can have an agonistic effect in addition to antagonist activity, whereas letrozole results only in estrogen depletion was crucial to the response achieved when letrozole was combined with an MEK inhibitor. Our current observations indicate that subtle variations in mechanisms of action of outwardly similar regimens may have a major impact on outcome and that such translational knowledge is critical for optimizing a precision medicine strategy. KEY POINTS: This report describes the remarkable response of a patient with KRAS-mutated, estrogen receptor-positive low-grade serous ovarian cancer treated with trametinib (MEK inhibitor) and letrozole (aromatase inhibitor), despite prior progression on similar agents including tamoxifen (estrogen modulator). In vitro investigation revealed that tamoxifen can have agonistic in addition to antagonistic effects, which could be the reason for the patient not responding to the combination of trametinib and tamoxifen. The current observations suggest that drugs with different mechanisms of action targeting the same receptor may have markedly different anticancer activity when used in combinations.
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http://dx.doi.org/10.1002/onco.13702DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8018312PMC
April 2021

A randomized trial of physical activity for cognitive functioning in breast cancer survivors: Rationale and study design of I Can! Improving Cognition After Cancer.

Contemp Clin Trials 2021 03 24;102:106289. Epub 2021 Jan 24.

UC San Diego Moores Cancer Center, UC San Diego, La Jolla, CA, USA.

Introduction: Difficulties with cognition are extremely common among breast cancer survivors and can significantly impact quality of life, daily functioning, and ability to return to work. One promising intervention is increasing physical activity, as it has been effective in improving cognition in non-cancer populations. Few physical activity intervention trials with cognition outcomes have included cancer survivors. This project builds upon our previous work indicating that increased physical activity can improve objectively measured processing speed and self-reported cognition among breast cancer survivors.

Methods: The I Can! study will examine whether a physical activity intervention improves cognition among 250 post-treatment breast cancer survivors (Stages I-III, <5 years post-treatment) who are reporting cognitive difficulties. This 2-arm randomized controlled trial comparing a 6-month physical activity intervention (Exercise Group) to a health & wellness attention-comparison condition (Health & Wellness Group) will examine intervention effects on cognition (at 3 and 6 months) and maintenance of effects at 12 months. The primary aim is to investigate the impact of exercise on objectively measured processing speed and self-reported cognition. Secondary aims are to investigate maintenance of cognitive changes and examine candidate biological mechanisms and psychological mediators.

Conclusion: The I Can! study will contribute to the scientific, public health, and survivorship intervention literature by providing new information on the impact of physical activity for cognitive impairment in breast cancer survivors. Findings from this study will inform guidelines for physical activity to improve the lives of millions of breast cancer survivors.
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http://dx.doi.org/10.1016/j.cct.2021.106289DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8009833PMC
March 2021

Cutaneous intralymphatic anaplastic lymphoma kinase-negative anaplastic large-cell lymphoma arising in a patient with multiple rounds of breast implants.

J Cutan Pathol 2021 May 22;48(5):659-662. Epub 2020 Dec 22.

Division of Blood and Marrow Transplant, Department of Medicine, University of California San Diego Health System, La Jolla, California, USA.

Primary cutaneous anaplastic large-cell lymphoma and breast implant-associated ALCL (BIA-ALCL) are rare subtypes of anaplastic lymphoma kinase (ALK)-negative ALCLs originating from skin and breast implants, respectively. Herein, we report a unique case of cutaneous ALK-negative ALCL occurring in the skin of left medial breast from a patient with multiple rounds of bilateral breast implants and a history of breast carcinoma. The lymphoma cells are entirely confined to the lymphatic channels in the dermis, and the patient has no other areas of skin abnormality, no lymphadenopathy, peri-implant fluid accumulation, or masses from the bilateral capsules of implants. The differential diagnosis and its relationship with breast implants are further explored.
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http://dx.doi.org/10.1111/cup.13936DOI Listing
May 2021

Cardiac Adverse Events With Remdesivir in COVID-19 Infection.

Cureus 2020 Oct 24;12(10):e11132. Epub 2020 Oct 24.

Obstetrics and Gynaecology, AdventHealth Altamonte, Altamonte Springs, USA.

Since December 2019, coronavirus has gradually progressed to a pandemic with no efficacious treatment. Remdesivir is an antiviral medication and inhibitor of viral RNA dependent RNA polymerase with inhibitory action against SARS-CoV virus. Two patients diagnosed with coronavirus infection with worsening respiratory status were initiated with multimodality therapy with antibiotics, steroids and remdesivir. After initiation of remdesivir, the patients' developed bradycardia, with one of the two also showing signs of worsening QT interval. This reverted upon stopping remdesvir therapy. The prevalence of bradycardia with prolonged QT interval is not well-known yet with this medication.
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http://dx.doi.org/10.7759/cureus.11132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7682945PMC
October 2020

Methotrexate for Cornual Ectopic Pregnancy.

Cureus 2020 Aug 10;12(8):e9642. Epub 2020 Aug 10.

Obstetrics and Gynecology, Adventhealth Altamonte, Altamonte Springs, USA.

A 27-year-old pregnant female presented to the emergency department with pelvic pain and vaginal bleeding. At the time of diagnosis, she had an ectopic pregnancy in the right cornua 4 cm in size with a human chorionic gonadotropin (hCG) value of 14,438 international units per mL. The ectopic pregnancy was initially managed by intramuscular methotrexate. However, after 10 days, despite an hCG value drop to 409 international units per mL, an indication that methotrexate was working, the patient had a subsequent rupture with hemoperitoneum necessitating exploratory laparotomy and abdominal hysterectomy.
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http://dx.doi.org/10.7759/cureus.9642DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7480890PMC
August 2020

Bleeding After a Single Dose of Ketorolac in a Postoperative Patient.

Cureus 2020 Jun 30;12(6):e8919. Epub 2020 Jun 30.

Clinical Pharmacy, AdventHealth Orlando and Rockledge Regional Medical Center, Orlando, USA.

A 74-year-old male patient with extensive cardiac history and hepatitis on apixaban and clopidogrel presented with adhesive small bowel obstruction. The patient underwent an exploratory laparotomy and adhesiolysis for small bowel obstruction. On postoperative day 6, after a single dose of ketorolac, the patient had an intra-abdominal bleed requiring exploratory laparotomy and washout.
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http://dx.doi.org/10.7759/cureus.8919DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7392184PMC
June 2020

Rectus Sheath Hematoma Causing Bladder Outlet Obstruction.

Cureus 2020 May 5;12(5):e7974. Epub 2020 May 5.

General Surgery, Boca Raton Regional Hospital, Boca Raton, USA.

A 93-year-old woman on Coumadin with history of atrial fibrillation and chronic obstructive pulmonary disease (COPD) presented with urinary retention for one day. Computed tomography (CT) of abdomen and pelvis demonstrated grade 3 rectus sheath hematoma (RSH), with the hematoma dissecting between the transversalis fascia and muscle into the prevesical space. The large-sized hematoma caused compression at the bladder outflow tract causing urinary retention. In view of age and the patient being a poor surgical candidate, the patient was managed by percutaneous drain of the hematoma to reduce size to relieve urinary symptoms. The hematoma shrunk in size over the period of next few weeks and thereby avoided surgical intervention.
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http://dx.doi.org/10.7759/cureus.7974DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7273386PMC
May 2020

Antagonistic Roles of GRK2 and GRK5 in Cardiac Aldosterone Signaling Reveal GRK5-Mediated Cardioprotection via Mineralocorticoid Receptor Inhibition.

Int J Mol Sci 2020 Apr 20;21(8). Epub 2020 Apr 20.

Laboratory for the Study of Neurohormonal Control of the Circulation, Department of Pharmaceutical Sciences, College of Pharmacy, Nova Southeastern University, Fort Lauderdale, FL 33328, USA.

Aldosterone (Aldo), when overproduced, is a cardiotoxic hormone underlying heart failure and hypertension. Aldo exerts damaging effects via the mineralocorticoid receptor (MR) but also activates the antiapoptotic G protein-coupled estrogen receptor (GPER) in the heart. G protein-coupled receptor (GPCR)-kinase (GRK)-2 and -5 are the most abundant cardiac GRKs and phosphorylate GPCRs as well as non-GPCR substrates. Herein, we investigated whether they phosphorylate and regulate cardiac MR and GPER. To this end, we used the cardiomyocyte cell line H9c2 and adult rat ventricular myocytes (ARVMs), in which we manipulated GRK5 protein levels via clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 and GRK2 activity via pharmacological inhibition. We report that GRK5 phosphorylates and inhibits the cardiac MR whereas GRK2 phosphorylates and desensitizes GPER. In H9c2 cardiomyocytes, GRK5 interacts with and phosphorylates the MR upon β-adrenergic receptor (AR) activation. In contrast, GRK2 opposes agonist-activated GPER signaling. Importantly, GRK5-dependent MR phosphorylation of the MR inhibits transcriptional activity, since aldosterone-induced gene transcription is markedly suppressed in GRK5-overexpressing cardiomyocytes. Conversely, GRK5 gene deletion augments cardiac MR transcriptional activity. βAR-stimulated GRK5 phosphorylates and inhibits the MR also in ARVMs. Additionally, GRK5 is necessary for the protective effects of the MR antagonist drug eplerenone against Aldo-induced apoptosis and oxidative stress in ARVMs. In conclusion, GRK5 blocks the cardiotoxic MR-dependent effects of Aldo in the heart, whereas GRK2 may hinder beneficial effects of Aldo through GPER. Thus, cardiac GRK5 stimulation (e.g., via βAR activation) might be of therapeutic value for heart disease treatment via boosting the efficacy of MR antagonists against Aldo-mediated cardiac injury.
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http://dx.doi.org/10.3390/ijms21082868DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7215681PMC
April 2020

Routine Plasma-Based Genotyping to Comprehensively Detect Germline, Somatic, and Reversion Mutations among Patients with Advanced Solid Tumors.

Clin Cancer Res 2020 06 7;26(11):2546-2555. Epub 2020 Feb 7.

Northwestern University Feinberg School of Medicine, Chicago, Illinois.

Purpose: PARP inhibitors (PARPi) are efficacious in multiple cancers harboring germline (and possibly somatic) mutations. Acquired reversions can restore function, causing resistance to PARPi and/or platinum-based chemotherapy. The optimal method of identifying patients with germline, somatic, and/or reversion mutations in has not been established. Next-generation sequencing (NGS) of cell-free DNA (cfDNA) provides a platform to identify these three types of mutations.

Experimental Design: Patients with advanced breast, ovarian, prostate, or pancreatic cancer were tested using a clinically validated 73-gene cfDNA assay that evaluates single-nucleotide variants and insertion-deletion mutations (indels) in , and distinguishes somatic/reversion from germline mutations with high accuracy.

Results: Among 828 patients, one or more deleterious mutations were detected in 60 (7.2%) patients, including germline ( = 42) and somatic ( = 18) mutations. Common coexisting mutations included (61.6%), (30%), (26.6%), (15%), and (11.5%). Polyclonal reversion mutations (median, 5) were detected in 9 of 42 (21.4%) germline mutant patients, the majority (77.7%) of whom had prior PARPi exposure (median duration, 10 months). Serial cfDNA demonstrated emergence of reversion mutations under therapeutic pressure from initial PARPi exposure, which contributed to subsequent resistance to PARPi and platinum therapy.

Conclusions: cfDNA NGS identified high rates of therapeutically relevant mutations without foreknowledge of germline or tissue-based testing results, including deleterious somatic mutations missed by germline testing and reversion mutations that can have important treatment implications. Further research is needed to confirm clinical utility of these findings to guide precision medicine approaches for patients with advanced malignancies.
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http://dx.doi.org/10.1158/1078-0432.CCR-19-2933DOI Listing
June 2020

GRK2-Mediated Crosstalk Between β-Adrenergic and Angiotensin II Receptors Enhances Adrenocortical Aldosterone Production In Vitro and In Vivo.

Int J Mol Sci 2020 Jan 16;21(2). Epub 2020 Jan 16.

Laboratory for the Study of Neurohormonal Control of the Circulation, Department of Pharmaceutical Sciences (Pharmacology), College of Pharmacy, Nova Southeastern University, Fort Lauderdale, FL 33328, USA.

Aldosterone is produced by adrenocortical zona glomerulosa (AZG) cells in response to angiotensin II (AngII) acting through its type I receptors (ATRs). ATR is a G protein-coupled receptor (GPCR) that induces aldosterone via both G proteins and the adapter protein βarrestin1, which binds the receptor following its phosphorylation by GPCR-kinases (GRKs) to initiate G protein-independent signaling. β-adrenergic receptors (ARs) also induce aldosterone production in AZG cells. Herein, we investigated whether GRK2 or GRK5, the two major adrenal GRKs, is involved in the catecholaminergic regulation of AngII-dependent aldosterone production. In human AZG (H295R) cells in vitro, the βAR agonist isoproterenol significantly augmented both AngII-dependent aldosterone secretion and synthesis, as measured by the steroidogenic acute regulatory (StAR) protein and CYP11B2 (aldosterone synthase) mRNA inductions. Importantly, GRK2, but not GRK5, was indispensable for the βAR-mediated enhancement of aldosterone in response to AngII. Specifically, GRK2 inhibition with Cmpd101 abolished isoproterenol's effects on AngII-induced aldosterone synthesis/secretion, whereas the GRK5 knockout via CRISPR/Cas9 had no effect. It is worth noting that these findings were confirmed in vivo, since rats overexpressing GRK2, but not GRK5, in their adrenals had elevated circulating aldosterone levels compared to the control animals. However, treatment with the β-blocker propranolol prevented hyperaldosteronism in the adrenal GRK2-overexpressing rats. In conclusion, GRK2 mediates a βAR-ATR signaling crosstalk in the adrenal cortex leading to elevated aldosterone production. This suggests that adrenal GRK2 may be a molecular link connecting the sympathetic nervous and renin-angiotensin systems at the level of the adrenal cortex and that its inhibition might be therapeutically advantageous in hyperaldosteronism-related conditions.
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http://dx.doi.org/10.3390/ijms21020574DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7013621PMC
January 2020

Wnt5a induces ROR1 to recruit cortactin to promote breast-cancer migration and metastasis.

NPJ Breast Cancer 2019 25;5:35. Epub 2019 Oct 25.

1Moores Cancer Center, University of California San Diego, La Jolla, CA USA.

ROR1 is a conserved oncoembryonic surface protein expressed in breast cancer. Here we report that ROR1 associates with cortactin in primary breast-cancer cells or in MCF7 transfected to express ROR1. Wnt5a also induced ROR1-dependent tyrosine phosphorylation of cortactin (Y421), which recruited ARHGEF1 to activate RhoA and promote breast-cancer-cell migration; such effects could be inhibited by cirmtuzumab, a humanized mAb specific for ROR1. Furthermore, treatment of mice bearing breast-cancer xenograft with cirmtuzumab inhibited cortactin phosphorylation in vivo and impaired metastatic development. We established that the proline at 841 of ROR1 was required for it to recruit cortactin and ARHGEF1, activate RhoA, and enhance breast-cancer-cell migration in vitro or development of metastases in vivo. Collectively, these studies demonstrate that the interaction of ROR1 with cortactin plays an important role in breast-cancer-cell migration and metastasis.
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http://dx.doi.org/10.1038/s41523-019-0131-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6814774PMC
October 2019

Mediators of a Physical Activity Intervention on Cognition in Breast Cancer Survivors: Evidence From a Randomized Controlled Trial.

JMIR Cancer 2019 Oct 11;5(2):e13150. Epub 2019 Oct 11.

Department of Family Medicine and Public Health, University of California, San Diego, La Jolla, CA, United States.

Background: Emerging research suggests that increasing physical activity can help improve cognition among breast cancer survivors. However, little is known about the mechanism through which physical activity impacts cancer survivors' cognition.

Objective: The objective of this secondary analysis examined physical and psychological function potentially linking physical activity with changes in cognition among breast cancer survivors in a randomized controlled trial where the exercise arm had greater improvements in cognition than the control arm.

Methods: A total of 87 sedentary breast cancer survivors were randomized to a 12-week physical activity intervention (n=43) or control condition (n=44). Objectively measured processing speed (National Institutes of Health Toolbox Oral Symbol Digit), self-reported cognition (patient-reported outcomes measurement information system [PROMIS] cognitive abilities), PROMIS measures of physical and psychological function (depression, anxiety, fatigue, and physical functioning), and plasma biomarkers (brain-derived neurotrophic factor, homeostatic model assessment 2 of insulin resistance, and C-reactive protein [CRP]) were collected at baseline and 12 weeks. Linear mixed-effects models tested intervention effects on changes in physical and psychological function variables and biomarkers. Bootstrapping was used to assess mediation. Exploratory analyses examined self-reported cognitive abilities and processing speed as mediators of the intervention effect on physical functioning.

Results: Participants in the exercise arm had significantly greater improvements in physical functioning (beta=1.23; 95% CI 2.42 to 0.03; P=.049) and reductions in anxiety (beta=-1.50; 95% CI -0.07 to -2.94; P=.04) than those in the control arm. Anxiety significantly mediated the intervention effect on cognitive abilities (bootstrap 95% CI -1.96 to -0.06), whereas physical functioning did not (bootstrap 95% CI -1.12 to 0.10). Neither anxiety (bootstrap 95% CI -1.18 to 0.74) nor physical functioning (bootstrap 95% CI -2.34 to 0.15) mediated the intervention effect on processing speed. Of the biomarkers, only CRP had greater changes in the exercise arm than the control arm (beta=.253; 95% CI -0.04 to 0.57; P=.09), but CRP was not associated with cognition; therefore, none of the biomarker measures mediated the intervention effect on cognition. Neither cognitive abilities (bootstrap 95% CI -0.06 to 0.68) nor processing speed (bootstrap 95% CI -0.15 to 0.63) mediated the intervention effect on physical function.

Conclusions: Physical activity interventions may improve self-reported cognition by decreasing anxiety. If supported by larger studies, reducing anxiety may be an important target for improving self-reported cognition among cancer survivors.

Trial Registration: ClinicalTrials.gov NCT02332876; https://clinicaltrials.gov/ct2/show/NCT02332876.
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http://dx.doi.org/10.2196/13150DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6914286PMC
October 2019

Research-based PAM50 signature and long-term breast cancer survival.

Breast Cancer Res Treat 2020 Jan 21;179(1):197-206. Epub 2019 Sep 21.

Department of Family Medicine and Public Health, University of California, San Diego, 3855 Health Sciences Drive #0901, La Jolla, CA, 92093-0901, USA.

Purpose: Multi-gene signatures provide biological insight and risk stratification in breast cancer. Intrinsic molecular subtypes defined by mRNA expression of 50 genes (PAM50) are prognostic in hormone-receptor positive postmenopausal breast cancer. Yet, for 25-40% in the PAM50 intermediate risk group, long-term risk remains uncertain. Our study aimed to (i) test the long-term prognostic value of the PAM50 signature in pre- and post-menopausal breast cancer; (ii) investigate if the PAM50 model could be improved by addition of other mRNAs implicated in oncogenesis.

Methods: We used archived FFPE samples from 1723 breast cancer survivors; high quality reads were obtained on 1253 samples. Transcript expression was quantified using a custom codeset with probes for > 100 targets. Cox models assessed gene signatures for breast cancer relapse and survival.

Results: Over 15 + years of follow-up, PAM50 subtypes were (P < 0.01) associated with breast cancer outcomes after accounting for tumor stage, grade and age at diagnosis. Results did not differ by menopausal status at diagnosis. Women with Luminal B (versus Luminal A) subtype had a > 60% higher hazard. Addition of a 13-gene hypoxia signature improved prognostication with > 40% higher hazard in the highest vs lowest hypoxia tertiles.

Conclusions: PAM50 intrinsic subtypes were independently prognostic for long-term breast cancer survival, irrespective of menopausal status. Addition of hypoxia signatures improved risk prediction. If replicated, incorporating the 13-gene hypoxia signature into the existing PAM50 risk assessment tool, may refine risk stratification and further clarify treatment for breast cancer.
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http://dx.doi.org/10.1007/s10549-019-05446-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6985186PMC
January 2020

Randomized Trial of Standard Adjuvant Chemotherapy Regimens Versus Capecitabine in Older Women With Early Breast Cancer: 10-Year Update of the CALGB 49907 Trial.

J Clin Oncol 2019 09 24;37(26):2338-2348. Epub 2019 Jul 24.

University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, NC.

Purpose: Older women with breast cancer remain under-represented in clinical trials. The Cancer and Leukemia Group B 49907 trial focused on women age 65 years and older. We previously reported the primary analysis after a median follow-up of 2.4 years. Standard adjuvant chemotherapy showed significant improvements in recurrence-free survival (RFS) and overall survival compared with capecitabine. We now update results at a median follow-up of 11.4 years.

Patients And Methods: Patients age 65 years or older with early breast cancer were randomly assigned to either standard adjuvant chemotherapy (physician's choice of either cyclophosphamide, methotrexate, and fluorouracil or cyclophosphamide and doxorubicin) or capecitabine. An adaptive Bayesian design was used to determine sample size and test noninferiority of capecitabine. The primary end point was RFS.

Results: The design stopped accrual with 633 patients at its first sample size assessment. RFS remains significantly longer for patients treated with standard chemotherapy. At 10 years, in patients treated with standard chemotherapy versus capecitabine, the RFS rates were 56% and 50%, respectively (hazard ratio [HR], 0.80; = .03); breast cancer-specific survival rates were 88% and 82%, respectively (HR, 0.62; = .03); and overall survival rates were 62% and 56%, respectively (HR, 0.84; = .16). With longer follow-up, standard chemotherapy remains superior to capecitabine among hormone receptor-negative patients (HR, 0.66; = .02), but not among hormone receptor-positive patients (HR, 0.89; = .43). Overall, 43.9% of patients have died (13.1% from breast cancer, 16.4% from causes other than breast cancer, and 14.1% from unknown causes). Second nonbreast cancers occurred in 14.1% of patients.

Conclusion: With longer follow-up, RFS remains superior for standard adjuvant chemotherapy versus capecitabine, especially in patients with hormone receptor-negative disease. Competing risks in this older population dilute overall survival benefits.
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http://dx.doi.org/10.1200/JCO.19.00647DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6900836PMC
September 2019

miRNAs and Long-term Breast Cancer Survival: Evidence from the WHEL Study.

Cancer Epidemiol Biomarkers Prev 2019 09 11;28(9):1525-1533. Epub 2019 Jun 11.

Department of Family Medicine and Public Health, University of California, San Diego, La Jolla, California.

Background: There is substantial variation in breast cancer survival rates, even among patients with similar clinical and genomic profiles. New biomarkers are needed to improve risk stratification and inform treatment options. Our aim was to identify novel miRNAs associated with breast cancer survival and quantify their prognostic value after adjusting for established clinical factors and genomic markers.

Methods: Using the Women's Healthy Eating and Living (WHEL) breast cancer cohort with >15 years of follow-up and archived tumor specimens, we assayed PAM50 mRNAs and 25 miRNAs using the Nanostring nCounter platform.

Results: We obtained high-quality reads on 1,253 samples (75% of available specimens) and used an existing research-use algorithm to ascertain PAM50 subtypes and risk scores (ROR-PT). We identified miRNAs significantly associated with breast cancer outcomes and then tested these in independent TCGA samples. miRNAs that were also prognostic in TCGA samples were further evaluated in multiple regression Cox models. We also used penalized regression for unbiased discovery.

Conclusions: Two miRNAs, 210 and 29c, were associated with breast cancer outcomes in the WHEL and TCGA studies and further improved risk stratification within PAM50 risk groups: 10-year survival was 62% in the node-negative high miR-210-high ROR-PT group versus 75% in the low miR-210- high ROR-PT group. Similar results were obtained for miR-29c. We identified three additional miRNAs, 187-3p, 143-3p, and 205-5p, via penalized regression.

Impact: Our findings suggest that miRNAs might be prognostic for long-term breast cancer survival and might improve risk stratification. Further research to incorporate miRNAs into existing clinicogenomic signatures is needed.
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http://dx.doi.org/10.1158/1055-9965.EPI-18-1322DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6726562PMC
September 2019

Continuous, objective measurement of physical activity during chemotherapy for breast cancer: the Activity in Treatment pilot study.

Transl Behav Med 2020 10;10(4):1031-1038

Department of Family Medicine and Public Health, UC San Diego, La Jolla, CA, USA.

Despite many potential benefits of physical activity during and after breast cancer treatment, activity levels typically decline from pre- to posttreatment. Most previous research has relied on self-reported activity. The purpose of this study were to assess patterns of daily, to objectively measured physical activity throughout chemotherapy for breast cancer, and to identify predictors of physical activity patterns. Participants were given a Fitbit before starting chemotherapy and asked to wear it throughout chemotherapy. Restricted cubic splines assessed nonlinear patterns of Fitbit measured total physical activity (TPA) and moderate-to-vigorous physical activity (MVPA) throughout the duration of chemotherapy (mean = 17 weeks, standard deviation [SD] = 6.3). Mixed-effects regression models assessed the rate of physical activity decline. Regressions of subject-level random slope assessed predictors of the rate of physical activity decline on participant and cancer characteristics and self-reported physical and cognitive functioning. Participants (n = 32) were on average 50 years old; the majority had stage II breast cancer. MVPA declined linearly at a mean rate of 1.4 min/day (p = .002) for every 10% of chemotherapy completed, whereas TPA declined linearly at an average rate of 13.4 min/day (p = .0007) for every 10% of chemotherapy completed, until around halfway through chemotherapy, when activity rates leveled off. HER+ receptor status was associated with a greater rate of MVPA decline, β = 13.3, p = .04. This novel study of objectively measured daily MVPA throughout chemotherapy showed that most reductions in activity occurred during the first half of a course of chemotherapy. Targeting this early period of chemotherapy may be important for preventing declines in activity levels throughout chemotherapy.
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http://dx.doi.org/10.1093/tbm/ibz079DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7543083PMC
October 2020

The effects of weight loss and metformin on cognition among breast cancer survivors: Evidence from the Reach for Health study.

Psychooncology 2019 08 27;28(8):1640-1646. Epub 2019 Jun 27.

Department of Family Medicine and Public Health, UC San Diego, La Jolla, California.

Objective: Breast cancer survivors experience problems with cognition that interfere with daily life and can last for years. In the general population, obesity and diabetes are risk factors for cognitive decline, and weight loss can improve cognition; however, the impact of intentional weight loss on cancer survivors' cognition has not been tested. We investigated the impact of weight loss and metformin on changes in cognitive function in a sample of breast cancer survivors.

Methods: Overweight/obese postmenopausal breast cancer survivors (n = 333) were randomized to a weight loss intervention versus control and metformin versus placebo in a 2 × 2 factorial design. Outcomes were changes in five cognitive domains from baseline to 6 months measured by objective neurocognitive tests.

Results: There were no statistically significant intervention effects for the metformin or weight loss interventions in five neurocognitive domains. Baseline body mass index (BMI) was a significant effect modifier of the changes in verbal functioning for the weight loss (P = 0.009) and metformin interventions (P = 0.0125). These effect modifications were independent of percent weight loss achieved during the 6-month study period.

Conclusions: This randomized controlled trial of weight loss and metformin interventions that examined changes to cognition among breast cancer survivors suggests that these interventions may not improve cognitive functioning among breast cancer survivors in general. However, weight loss may improve verbal functioning among individuals with a higher BMI.
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http://dx.doi.org/10.1002/pon.5129DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6791123PMC
August 2019

Contraceptive utilization and counseling among breast cancer survivors.

J Cancer Surviv 2019 06 8;13(3):438-446. Epub 2019 May 8.

Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Stanford University, Stanford, CA, USA.

Purpose: To explore contraceptive counseling and utilization among breast cancer survivors.

Methods: We enrolled reproductive-aged women with a history of breast cancer for a cross-sectional study. Participants were recruited via the Athena Breast Health Network and via the Young Survival Coalition's social media postings. Descriptive statistics were calculated to understand utilization of and feelings about contraceptive methods before, during, and after breast cancer treatment.

Results: Data presented here are from an online survey of 150 breast cancer survivors who completed the survey. Seventy-one percent (n = 105) of respondents reported being sexually active and not pregnant during their primary cancer treatment (surgery, chemotherapy, and/or radiation). Of these, 90% (n = 94) reported using any form of contraceptive, and the most common method was condoms (n = 55, 52%). Respondents reported that safety concerns had the biggest influence on their contraception method choice. Sixty-one percent (n = 92) reported receiving contraceptive counseling by their oncologist either before or after treatment; however, 49% (n = 45) of those did not receive a specific recommendation for a contraceptive method. Of respondents who reported receiving contraceptive counseling from their gynecologist, 44% (n = 35) reported that their gynecologist specifically recommended a copper intrauterine device (IUD). The majority of respondents (n = 76, 52%) wanted their oncologist to discuss contraceptive options with them and preferred to receive this counseling at the time of diagnosis (n = 81, 57%).

Conclusions: Breast cancer survivors in this study remained sexually active across the cancer care continuum and predominantly used condoms as their contraceptive method during treatment. Breast cancer patients would prefer contraceptive counseling from their oncologist at the time of their cancer diagnosis.

Implication For Cancer Survivors: Education efforts in the future should focus on initiatives to improve comprehensive contraceptive counseling at the time of diagnosis by an oncologist.
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http://dx.doi.org/10.1007/s11764-019-00765-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6561485PMC
June 2019

Examining Indigenous food sovereignty as a conceptual framework for health in two urban communities in Northern Ontario, Canada.

Glob Health Promot 2019 04;26(3_suppl):54-63

1 Department of Indigenous Learning, Lakehead University, Ontario, Canada.

While land is a nexus for culture, identity, governance, and health, as a concept land is rarely addressed in conversations and policy decisions about Indigenous health and well-being. Indigenous food sovereignty, a concept which embodies Indigenous peoples' ability to control their food systems, including markets, production modes, cultures and environments, has received little attention as a framework to approach Indigenous health especially for Indigenous people living in urban spaces. Instead, discussions about Indigenous food sovereignty have largely focused on global and remote and rural communities. Addressing this gap in the literature, this article presents exploratory work conducted with Waasegiizhig Nanaandawe'iyewigamig and Shkagamik-Kwe Health Centre, two Indigenous-led Aboriginal Health Access Centres in urban service centers located in Northern Ontario, Canada.
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http://dx.doi.org/10.1177/1757975919831639DOI Listing
April 2019

Next-Generation Sequencing of Tissue and Circulating Tumor DNA: The UC San Diego Moores Center for Personalized Cancer Therapy Experience with Breast Malignancies.

Mol Cancer Ther 2019 05 29;18(5):1001-1011. Epub 2019 Mar 29.

University of California, San Diego, Moores Cancer Center, La Jolla, California.

Clinical-grade next-generation sequencing (NGS) of tissue- and blood-derived circulating tumor DNA (ctDNA) allows assessment of multiple genomic alterations in patients with cancer. We analyzed ctDNA (54-70 genes) in 62 patients with advanced breast cancer (median = five prior therapies); 38 also had tissue NGS (236-315 genes). Overall, 42 of 62 patients (68%) had detectable (characterized) ctDNA alterations (variants of unknown significance excluded), and 37 of 38 (97%) had tissue alterations. The median (range) number of characterized alterations in ctDNA was 1 (0-7), and in tissue, 4 (0-17). The most common alterations in ctDNA were in (37% of patients) and (23%), and for tissue, (37%) and (24%); amplification was seen in ctDNA (11%), but not in tissue. Concordance between ctDNA and tissue appeared higher if <6 months separated the sample acquisition, although small sample size precluded statistical validation. Overall, 32 of 67 tissue alterations (48%) were also detected in ctDNA; 35 of 72 ctDNA alterations (48%) were also in tissue. Excluding estrogen receptor and , 41 of 62 patients (66%) had potentially actionable alterations in ctDNA, and 36 of 38 (95%), in tissue (with potential actionability based on either preclinical or clinical evidence). If ≥1 genomic alteration had ctDNA ≥5%, survival was shorter than if ctDNA was <5% (median, 6.7 vs. 17.9 months; = 0.01). In conclusion, tissue and ctDNA NGS reveal potentially actionable alterations in most patients. The genomic results of ctDNA and tissue NGS overlap, but there are differences, perhaps reflecting temporal spacing and tumor heterogeneity. ctDNA quantification also provides prognostic information.
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http://dx.doi.org/10.1158/1535-7163.MCT-17-1038DOI Listing
May 2019

Deletion of Osteopontin Enhances β₂-Adrenergic Receptor-Dependent Anti-Fibrotic Signaling in Cardiomyocytes.

Int J Mol Sci 2019 Mar 20;20(6). Epub 2019 Mar 20.

Laboratory for the Study of Neurohormonal Control of the Circulation, Department of Pharmaceutical Sciences (Pharmacology), College of Pharmacy; Nova Southeastern University, Fort Lauderdale, FL 33328, USA.

Cardiac β₂-adrenergic receptors (ARs) are known to inhibit collagen production and fibrosis in cardiac fibroblasts and myocytes. The β₂AR is a Gs protein-coupled receptor (GPCR) and, upon its activation, stimulates the generation of cyclic 3',5'-adenosine monophosphate (cAMP). cAMP has two effectors: protein kinase A (PKA) and the exchange protein directly activated by cAMP (Epac). Epac1 has been shown to inhibit cardiac fibroblast activation and fibrosis. Osteopontin (OPN) is a ubiquitous pro-inflammatory cytokine, which also mediates fibrosis in several tissues, including the heart. OPN underlies several cardiovascular pathologies, including atherosclerosis and cardiac adverse remodeling. We found that the cardiotoxic hormone aldosterone transcriptionally upregulates OPN in H9c2 rat cardiac myoblasts-an effect prevented by endogenous β₂AR activation. Additionally, CRISPR-mediated OPN deletion enhanced cAMP generation in response to both β₁AR and β₂AR activation in H9c2 cardiomyocytes, leading to the upregulation of Epac1 protein levels. These effects rendered β₂AR stimulation capable of completely abrogating transforming growth factor (TGF)-β-dependent fibrosis in OPN-lacking H9c2 cardiomyocytes. Finally, OPN interacted constitutively with Gs subunits in H9c2 cardiac cells. Thus, we uncovered a direct inhibitory role of OPN in cardiac β₂AR anti-fibrotic signaling via cAMP/Epac1. OPN blockade could be of value in the treatment and/or prevention of cardiac fibrosis.
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http://dx.doi.org/10.3390/ijms20061396DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6470638PMC
March 2019

Inhibition of chemotherapy resistant breast cancer stem cells by a ROR1 specific antibody.

Proc Natl Acad Sci U S A 2019 01 8;116(4):1370-1377. Epub 2019 Jan 8.

Guangdong Key Laboratory for Genome Stability and Human Disease Prevention, Department of Pharmacology, International Cancer Center, Shenzhen University Health Science Center, 518060 Shenzhen, China;

Breast cancers enduring treatment with chemotherapy may be enriched for cancer stem cells or tumor-initiating cells, which have an enhanced capacity for self-renewal, tumor initiation, and/or metastasis. Breast cancer cells that express the type I tyrosine kinaselike orphan receptor ROR1 also may have such features. Here we find that the expression of ROR1 increased in breast cancer cells following treatment with chemotherapy, which also enhanced expression of genes induced by the activation of Rho-GTPases, Hippo-YAP/TAZ, or B lymphoma Mo-MLV insertion region 1 homolog (BMI1). Expression of ROR1 also enhanced the capacity of breast cancer cells to invade Matrigel, form spheroids, engraft in Rag2[Formula: see text] mice, or survive treatment with paclitaxel. Treatment of mice bearing breast cancer patient-derived xenografts (PDXs) with the humanized anti-ROR1 monoclonal antibody cirmtuzumab repressed expression of genes associated with breast cancer stemness, reduced activation of Rho-GTPases, Hippo-YAP/TAZ, or BMI1, and impaired the capacity of breast cancer PDXs to metastasize or reengraft Rag2[Formula: see text] mice. Finally, treatment of PDX-bearing mice with cirmtuzumab and paclitaxel was more effective than treatment with either alone in eradicating breast cancer PDXs. These results indicate that targeting ROR1 may improve the response to chemotherapy of patients with breast cancer.
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http://dx.doi.org/10.1073/pnas.1816262116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6347692PMC
January 2019

Novel Insights into the Crosstalk between Mineralocorticoid Receptor and G Protein-Coupled Receptors in Heart Adverse Remodeling and Disease.

Int J Mol Sci 2018 Nov 27;19(12). Epub 2018 Nov 27.

Laboratory for the Study of Neurohormonal Control of the Circulation, Department of Pharmaceutical Sciences (Pharmacology), College of Pharmacy, Nova Southeastern University, Fort Lauderdale, FL 33328, USA.

The mineralocorticoid hormone aldosterone regulates sodium and potassium homeostasis but also adversely modulates the maladaptive process of cardiac adverse remodeling post-myocardial infarction. Through activation of its mineralocorticoid receptor (MR), a classic steroid hormone receptor/transcription factor, aldosterone promotes inflammation and fibrosis of the heart, the vasculature, and the kidneys. This is why MR antagonists reduce morbidity and mortality of heart disease patients and are part of the mainstay pharmacotherapy of advanced human heart failure. A plethora of animal studies using cell type⁻specific targeting of the MR gene have established the importance of MR signaling and function in cardiac myocytes, vascular endothelial and smooth muscle cells, renal cells, and macrophages. In terms of its signaling properties, the MR is distinct from nuclear receptors in that it has, in reality, two physiological hormonal agonists: not only aldosterone but also cortisol. In fact, in several tissues, including in the myocardium, cortisol is the primary hormone activating the MR. There is a considerable amount of evidence indicating that the effects of the MR in each tissue expressing it depend on tissue- and ligand-specific engagement of molecular co-regulators that either activate or suppress its transcriptional activity. Identification of these co-regulators for every ligand that interacts with the MR in the heart (and in other tissues) is of utmost importance therapeutically, since it can not only help elucidate fully the pathophysiological ramifications of the cardiac MR's actions, but also help design and develop novel better MR antagonist drugs for heart disease therapy. Among the various proteins the MR interacts with are molecules involved in cardiac G protein-coupled receptor (GPCR) signaling. This results in a significant amount of crosstalk between GPCRs and the MR, which can affect the latter's activity dramatically in the heart and in other cardiovascular tissues. This review summarizes the current experimental evidence for this GPCR-MR crosstalk in the heart and discusses its pathophysiological implications for cardiac adverse remodeling as well as for heart disease therapy. Novel findings revealing non-conventional roles of GPCR signaling molecules, specifically of GPCR-kinase (GRK)-5, in cardiac MR regulation are also highlighted.
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http://dx.doi.org/10.3390/ijms19123764DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6320977PMC
November 2018

Authentic practice environments to support undergraduate nursing students' readiness for hospital placements. A new model of practice in an on campus simulated hospital and health service.

Nurse Educ Pract 2018 Nov 8;33:47-54. Epub 2018 Sep 8.

Nursing and Midwifery, Level 6 City East Campus, North Terrace, Adelaide, SA, 5000, Australia. Electronic address:

This paper reports on a unique practice based learning model to prepare undergraduate nursing students for clinical placement. The learning and teaching model described in this paper outlines the establishment of an entire on-campus simulated hospital and health service (SHHS) at the University of South Australia, School of Nursing and Midwifery. The model is pedagogically structured to immerse students in an authentic clinical environment to achieve deep learning in preparation for safe practice. A quality improvement cycle was used to evaluate the outcomes of the model in two phases: Phase 1: Purposive sampling of first and second year Bachelor of Nursing students from 2012 to 2015 who were surveyed about their satisfaction with the model of learning. Bachelor of Nursing students were invited to complete a survey about their experience with the teaching and learning model employed in the SHHS in response to the question, 'What aspects of the SHHS are the most important to your success?' Phase 2: External clinical stakeholders working with nursing students in clinical placements were asked to respond to questions about the preparedness of students educated in this model to transition to employment. The evaluation showed that the SHHS model positively influenced students' satisfaction and confidence and increased the perception of clinicians of the work readiness of students.
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http://dx.doi.org/10.1016/j.nepr.2018.08.012DOI Listing
November 2018
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