The impact of the Prime Time Sister Circles® (PTSC) on blood pressure of low-income mid-life African American women in the United States.

There is a pressing need to develop and evaluate culturally tailored, community-based interventions that address hypertension management among low-income African American women. We employed a randomized controlled trial to test the effectiveness of the Prime Time Sister Circles® Program in reducing blood pressure and body mass index among low-income African American women ages with hypertension. Study participants (N = 339) were African American women aged 40-75 years who were diagnosed with hypertension and received their primary care at government funded health centers in Washington, D.C. Compared to the usual care group, Prime Time Sister Circles® participation was associated with a reduction in systolic BP by - 2.45 (CI - 6.13, 1.23) mmHg, a reduction in diastolic BP by - 3.66 mmHg (CI - 6.32, - 0.99), and a change in BMI by - 0.26 (CI - 2.00, 1.48) from baseline to 15 months. The results suggest that culturally tailored community-based interventions can improve hypertension management in low-income women.

Evaluating the Impact of the Prime Time Sister Circles® Intervention on Reducing Depressive Symptoms Among African American Women with Uncontrolled Hypertension.

BACKGROUND: The Prime Time Sister Circles®, a randomized controlled trial (PTSC-RCT), assessed the impact of a community-based peer support program on hypertension management among African American women 40-75 years of age. While the PTSC-RCT was designed to evaluate changes in blood pressure control, subsequent sub-analyses revealed a high proportion of self-reported depressive symptoms in our sample. Accordingly, we conducted an ancillary investigation of the PTSC intervention on depression to ascertain its impact on reduced depressive symptoms in the study population. METHOD: Depressive symptoms were measured using an adapted version of the Center for Epidemiologic Studies Depression Scale Revised (CES-D-10). We used unadjusted and adjusted fixed effect models. Data for this study came from the PTSC-RCT. We collected data between 2017 and 2018 in Washington, DC. We used a balanced analytical sample of 172 African American, English-speaking women between 40 to 75 years old with uncontrolled hypertension. INTERVENTION: The intervention group participated in a 2-h, peer-based support group once a week for 13 weeks. A trained PTSC facilitator facilitated sessions with experts who delivered content on various topics, including psychosocial wellness (e.g., stress, depressive symptoms, anxiety management, and self-esteem), physical health (e.g., hypertension, inflammation, and heart disease), physical activity, and healthy nutrition. RESULTS: Results from the fixed-effects models indicated that participants in the PTSC program exhibited a greater reduction in CES-D-10 score at three months (Coeff: -1.99, 95% CI: -3.49, -0.49) and at 15 months (Coeff: -2.38, 95% CI: -3.94, -0.83), as compared to those in the control group. CONCLUSIONS: Evidence suggests that the Prime Time Sister Circles® intervention reduced depressive symptoms among African American women with low socioeconomic status and hypertension. TRIAL REGISTRATION: NCT04371614.

Use of Voice-Assisted Technology to Enhance the Home Health Care Patient Experience.

One of the greatest challenges for older, homebound patients receiving health care is accessibility, particularly following a hospitalization. The current study evaluates the effects of using voice-activated technology in the homes of recently discharged patients and its effects on health care outcomes. Voice-based software was embedded in a smart device, which allowed patients to ask questions and receive answers about their own specific care plan. A pre-post study design was used. Forty-eight patients completed the pre and post survey. There was a 63% reduction in emergency department visits and a 26% reduction in physician calls. There was no change in the number of patients requiring hospitalization. More than one half of patients used the smart device daily for their health care needs. More than 70% of patients believed the device was helpful for their general health care needs and assisted in the achievement of care goals. This is the first study of its kind to evaluate patient engagement and outcomes after the use of a smart device with embedded health care directions. [Journal of Gerontological Nursing, 48(12), 17-24.].

Study protocol of a randomized controlled trial evaluating the Prime Time Sister Circles (PTSC) program's impact on hypertension among midlife African American women.

BACKGROUND: The Prime-Time Sister Circles® (PTSC) program is a multifaceted, community-based peer support intervention targeting African American women who are 40 to 75 years of age. It aims to reduce hypertension disparities observed among African American women by promoting adherence to antihypertensive therapies, including lifestyle modification and therapeutic regimens. METHODS: The PTSC randomized controlled trial will evaluate the effectiveness of the PTSC Program on improved blood pressure control, healthcare utilization attributed to cardiovascular events, and healthcare costs. The study began in 2016 and will end in 2022. African American women who are 40-75 years old, have been diagnosed with hypertension, reside in Washington, D.C. or Baltimore, Maryland, and receive their care from Unity Health Care, a federally qualified health center in Washington, D.C., or Baltimore Medical System, a federally qualified health center in Baltimore, Maryland, are eligible to participate. Those randomized to the intervention group participate in the PTSC Program, which spans 13 weeks and comprises facilitator-led discussions, didactic training about hypertension management, and peer-based problem-solving concerning CVD risk factors and their amelioration. Blood pressure, weight, body mass index, waist circumference, self-reported adherence, physical activity, dietary practices, stress, and healthcare utilization data are collected at baseline, 13 weeks (end of the intervention), 9 months (months post-intervention), and 15 months (one year after the intervention). Healthcare costs will be computed at the end of the study. The study's design is reported in the present manuscript, wherein we employed the SPIRIT checklist to guide its construction. DISCUSSION: Disparities in hypertension prevalence and management observed among mid-life African American women exist as a result of a confluence of structural determinants of health. Consequently, there is a need to develop, implement, and evaluate culturally appropriate and relevant interventions that are tailored to their lived experiences. The PTSC Trial aims to assess the impact of the program on participants' cardiovascular, psychosocial, and cost outcomes. Its results have implications for advancing the science of designing and implementing culturally relevant interventions for African American women. TRIAL REGISTRATION: Unique identifier: NCT04371614 . Retrospectively registered on April 30, 2020.

Evaluating Depressive Symptoms Among Low-Socioeconomic-Status African American Women Aged 40 to 75 Years With Uncontrolled Hypertension: A Secondary Analysis of a Randomized Clinical Trial.

Importance: Depression is one of the leading causes of disability in the United States. African American women of low socioeconomic status with uncontrolled hypertension are at risk of having severe depressive symptoms, yet there is limited research about the mental health of this vulnerable population. Data from the Prime Time Sister Circles randomized clinical trial (PTSC-RCT) study can shed light on the prevalence of depressive symptoms among low-socioeconomic-status older African American women with hypertension. Objective: To determine the prevalence of depressive symptoms among low-socioeconomic-status African American women aged 40 to 75 years with uncontrolled hypertension who receive their care from a federally qualified health center (FQHC) and to identify risk factors associated with depressive symptoms. Design, Setting, and Participants: Cross-sectional analysis of data from the PTSC-RCT of depressive symptomology, measured using an adapted version of the 10-item Center for Epidemiological Studies Depression Scale Revised (CES-D-10). Descriptive statistics were used to characterize the study population. We used logistic regression models to investigate the factors associated with participants with or without symptoms of depression. We used baseline data from the PTSC-RCT study, including 316 African American English-speaking women between ages 40 and 75 years with hypertension (systolic blood pressure ≥140 mm Hg or diastolic ≥90 mm Hg), who received their primary care at a FQHC in Washington, DC, in 2017 and 2018 and were flagged by the FQHC as uncontrolled. Main Outcomes and Measures: We used the CES-D-10 from the Center for Epidemiologic Studies Depression Scale to measure presence of depressive symptoms. Results: A total of 57.0% of the women in the study (180 of 316) scored greater than or equal to 10 on the CES-D-10. Depressive symptoms had a negative association with a postsecondary education (adjusted odds ratio [aOR], 0.492; 95% CI, 0.249-0.968) and a positive association with the number of chronic conditions (aOR, 1.235; 95% CI, 1.046-1.460) and smoking (aOR, 1.731; 95% CI, 1.039-2.881). Conclusions and Relevance: In this study of low-income African American women with uncontrolled hypertension, more than half had symptoms of depression that was associated with less than high-school education, chronic conditions, and smoking. Low-income African American women with uncontrolled hypertension should be screened and adequately treated for depressive symptoms. Trial Registration: ClinicalTrials.gov Identifier: NCT04371614.

ETS2 mediated tumor suppressive function and MET oncogene inhibition in human non-small cell lung cancer.

PURPOSE: The ETS2 transcription factor is an evolutionarily conserved gene that is deregulated in cancer. We analyzed the transcriptome of lung adenocarcinomas and normal lung tissue by expression profiling and found that ETS2 was significantly downregulated in adenocarcinomas. In this study, we probed the yet unknown functional role of ETS2 in lung cancer pathogenesis. EXPERIMENTAL DESIGN: Lung adenocarcinomas (n = 80) and normal lung tissues (n = 30) were profiled using the Affymetrix Human Gene 1.0 ST platform. Immunohistochemical (IHC) analysis was conducted to determine ETS2 protein expression in non-small cell lung cancer (NSCLC) histologic tissue specimens (n = 201). Patient clinical outcome, based on ETS2 IHC expression, was statistically assessed using the log-rank and Kaplan-Meier tests. RNA interference and overexpression strategies were used to assess the effects of ETS2 expression on the transcriptome and on various malignant phenotypes. RESULTS: ETS2 expression was significantly reduced in lung adenocarcinomas compared with normal lung (P < 0.001). Low ETS2 IHC expression was a significant predictor of shorter time to recurrence in NSCLC (P = 0.009, HR = 1.89) and adenocarcinoma (P = 0.03, HR = 1.86). Moreover, ETS2 was found to significantly inhibit lung cancer cell growth, migration, and invasion (P < 0.05), and microarray and pathways analysis revealed significant (P < 0.001) activation of the HGF pathway following ETS2 knockdown. In addition, ETS2 was found to suppress MET phosphorylation and knockdown of MET expression significantly attenuated (P < 0.05) cell invasion mediated by ETS2-specific siRNA. Furthermore, knockdown of ETS2 augmented HGF-induced MET phosphorylation, cell migration, and invasion. CONCLUSION(S): Our findings point to a tumor suppressor role for ETS2 in human NSCLC pathogenesis through inhibition of the MET proto-oncogene.

High expression of folate receptor alpha in lung cancer correlates with adenocarcinoma histology and EGFR [corrected] mutation.

INTRODUCTION: Folate receptor alpha (FRα) and reduced folate carrier-1 (RFC1) regulate uptake of folate molecules inside the cell. FRα is a potential biomarker of tumors response to antifolate chemotherapy, and a target for therapies using humanized monocloncal antibody. Information on the protein expression of these receptors in non-small-cell lung carcinoma (NSCLC) is limited. MATERIAL AND METHODS: Expressions of FRα and RFC1 were examined by immunohistochemistry (IHC) in 320 surgically resected NSCLC (202 adenocarcinomas and 118 squamous cell carcinomas) tissue specimens and correlated with patients' clinico-pathologic characteristics. Folate receptor α gene (FOLR1) mRNA expression was examined using publicly available microarray datasets. FRα expression was correlated with thymidylate synthase and p53 expression in NSCLCs, and with epidermal growth factor receptor (EGFR) and V-Ki-ras2 Kirsten rat sarcoma viral (KRAS) gene mutations in adenocarcinomas. RESULTS: NSCLC overexpressed FRα and RFC1. In a multivariate analysis, lung adenocarcinomas were more likely to express FRα in the cytoplasm (OR = 4.39; p < 0.0001) and membrane (OR = 5.34; p < 0.0001) of malignant cells than squamous cell carcinomas. Tumors from never-smokers were more likely to express cytoplasmic (OR = 3.35; p<0.03) and membrane (OR = 3.60; p=0.0005) FRα than those from smokers. In adenocarcinoma, EGFR mutations correlated with higher expression of membrane FRα and FOLR1 gene expressions. High levels of FRα expression was detected in 42 NSCLC advanced metastatic tumor tissues. CONCLUSIONS: FRα and RFC1 proteins are overexpressed in NSCLC tumor tissues. The high levels of FRα in lung adenocarcinomas may be associated to these tumors' better responses to antifolate chemotherapy and represents a potential novel target for this tumor type.

HER family receptor and ligand status in thymic carcinoma.

Overexpression and gene amplification of the HER family of receptors and their ligands are important prognostic factors in many solid tumors and treatment targeting these molecules has recently become available. The role of this group of receptors has only rarely been described in thymic epithelial neoplasms and never before in a series of cases consisting exclusively of thymic carcinoma. Twenty-four primary squamous cell carcinomas of the thymus were examined for immunohistochemical expression of epidermal growth factor receptor (EGFR), phosphorylated EGFR (pEGFR), HER2, phosphorylated HER2 (pHER2), HER3, phosphorylated HER3 (pHER3) and their ligands epidermal growth factor (EGF), transforming growth factor-α (TGF-α), amphiregulin and epiregulin. Fluorescence in situ hybridization (FISH) analysis for amplification of the EGFR and HER2 genes was performed including assessment of the copy numbers of EGFR and HER2 gene per cell and the ratio of EGFR and HER2 to centromere 7 and 17, respectively. Significant immunohistochemical expression was observed for EGFR (33.3%), pEGFR (33.3%), HER2 (58.3%), HER3 (45.8%), TGF-α (54.1%), amphiregulin (25.0%) and epiregulin (91.7%). A single case showed HER2 gene amplification by FISH. Increased EGFR and HER2 gene copy numbers were observed in 2 (8.4%) and 18 cases (75%), respectively. Eight cases (33.3%) showed an increased HER2:CEP17 ratio. The results of this study indicate that EGFR and HER2 amplification is a rare event in thymic carcinoma, however, protein expression for HER receptors as well as their ligands is a common finding indicating that targeted therapy directed against these molecules may be considered in the treatment of these tumors.

STAT5A-mediated SOCS2 expression regulates Jak2 and STAT3 activity following c-Src inhibition in head and neck squamous carcinoma.

PURPOSE: The inhibition of c-Src results in a striking reduction in cancer cell invasion, but the effect on cell survival is modest. Defining mechanisms that limit apoptosis following c-Src inhibition could result in an ideal therapeutic approach that both inhibits invasion and leads to apoptosis. In this regard, we discovered a novel feedback loop that results in STAT3 reactivation following sustained c-Src inhibition. Here we define the mechanism underlying this feedback loop and examine the effect of inhibiting it in vivo. EXPERIMENTAL DESIGN: We measured levels and activity of pathway components using PCR, Western blotting, and kinase assays following their manipulation using both molecular and pharmacologic approaches. We used a heterotransplant animal model in which human oral squamous cancer is maintained exclusively in vivo. RESULTS: Following c-Src inhibition, STAT5 is durably inhibited. The inhibition of STAT5A, but not STAT5B, subsequently reduces the expression of suppressors of cytokine signaling 2 (SOCS2). SOCS2 inhibits Janus kinase 2 (Jak2) activity and Jak2-STAT3 binding. SOCS2 expression is necessary for STAT3 inhibition by c-Src inhibitors. Overexpression of SOCS2 is adequate to prevent STAT3 reactivation and to enhance the cytotoxic effects of c-Src inhibition. Likewise, the combination of Jak and c-Src inhibitors led to significantly more apoptosis than either agent alone in vivo. CONCLUSIONS: To our knowledge, ours is the first study that fully defines the mechanism underlying this feedback loop, in which sustained c-Src inhibition leads to diminished SOCS2 expression via sustained inhibition of STAT5A, allowing activation of Jak2 and STAT3, Jak2-STAT3 binding, and survival signals.

Sex determining region Y-Box 2 (SOX2) is a potential cell-lineage gene highly expressed in the pathogenesis of squamous cell carcinomas of the lung.

BACKGROUND: Non-small cell lung cancer (NSCLC) represents the majority (85%) of lung cancers and is comprised mainly of adenocarcinomas and squamous cell carcinomas (SCCs). The sequential pathogenesis of lung adenocarcinomas and SCCs occurs through dissimilar phases as the former tumors typically arise in the lung periphery whereas the latter normally arise near the central airway. METHODOLOGY/PRINCIPAL FINDINGS: We assessed the expression of SOX2, an embryonic stem cell transcriptional factor that also plays important roles in the proliferation of basal tracheal cells and whose expression is restricted to the main and central airways and bronchioles of the developing and adult mouse lung, in NSCLC by various methodologies. Here, we found that SOX2 mRNA levels, from various published datasets, were significantly elevated in lung SCCs compared to adenocarcinomas (all p<0.001). Moreover, a previously characterized OCT4/SOX2/NANOG signature effectively separated lung SCCs from adenocarcinomas in two independent publicly available datasets which correlated with increased SOX2 mRNA in SCCs. Immunohistochemical analysis of various histological lung tissue specimens demonstrated marked nuclear SOX2 protein expression in all normal bronchial epithelia, alveolar bronchiolization structures and premalignant lesions in SCC development (hyperplasia, dysplasia and carcinoma in situ) and absence of expression in all normal alveoli and atypical adenomatous hyperplasias. Moreover, SOX2 protein expression was greatly higher in lung SCCs compared to adenocarcinomas following analyses in two independent large TMA sets (TMA set I, n = 287; TMA set II, n = 511 both p<0.001). Furthermore, amplification of SOX2 DNA was detected in 20% of lung SCCs tested (n = 40) and in none of the adenocarcinomas (n = 17). CONCLUSIONS/SIGNIFICANCE: Our findings highlight a cell-lineage gene expression pattern for the stem cell transcriptional factor SOX2 in the pathogenesis of lung SCCs and suggest a differential activation of stem cell-related pathways between squamous cell carcinomas and adenocarcinomas of the lung.

Immunohistochemical expression of estrogen and progesterone receptors identifies a subset of NSCLCs and correlates with EGFR mutation.

PURPOSE: To determine the frequency of estrogen receptor alpha and beta and progesterone receptor protein immunohistochemical expression in a large set of non-small cell lung carcinoma (NSCLC) specimens and to compare our results with those for some of the same antibodies that have provided inconsistent results in previously published reports. EXPERIMENTAL DESIGN: Using multiple antibodies, we investigated the immunohistochemical expression of estrogen receptors alpha and beta and progesterone receptor in 317 NSCLCs placed in tissue microarrays and correlated their expression with patients' clinicopathologic characteristics and in adenocarcinomas with EGFR mutation status. RESULTS: Estrogen receptors alpha and beta were detected in the nucleus and cytoplasm of NSCLC cells; however, the frequency of expression (nucleus, 5-36% for alpha and 42-56% for beta; cytoplasm: <1-42% for alpha and 20-98% for beta) varied among the different antibodies tested. Progesterone receptor was expressed in the nuclei of malignant cells in 63% of the tumors. Estrogen receptor alpha nuclear expression significantly correlated with adenocarcinoma histology, female gender, and history of never smoking (P = 0.0048 to <0.0001). In NSCLC, higher cytoplasmic estrogen receptor alpha expression significantly correlated with worse recurrence-free survival (hazard ratio, 1.77; 95% confidence interval, 1.12, 2.82; P = 0.015) in multivariate analysis. In adenocarcinomas, estrogen receptor alpha expression correlated with EGFR mutation (P = 0.0029 to <0.0001). Estrogen receptor beta and progesterone receptor but not estrogen receptor alpha expressed in the normal epithelium adjacent to lung adenocarcinomas. CONCLUSIONS: Estrogen receptor alpha and beta expression distinguishes a subset of NSCLC that has defined clinicopathologic and genetic features. In lung adenocarcinoma, estrogen receptor alpha expression correlates with EGFR mutations.

Repeated intravesical instillations of an adenoviral vector in patients with locally advanced bladder cancer: a phase I study of p53 gene therapy.

PURPOSE: We investigated the feasibility, safety, and biologic activity of adenovirus-mediated p53 gene transfer in patients with locally advanced bladder cancer. PATIENTS AND METHODS: Patients with measurable, locally advanced transitional-cell carcinoma of the bladder who were not candidates for cystectomy were eligible. On a 28-day cycle, intravesical instillations of INGN 201 (Ad5CMV-p53) were administered on days 1 and 4 at three dose levels (10(10) particles to 10(12) particles) or on either 4 or 8 consecutive days at a single dose level (10(12) particles). RESULTS: Thirteen patients received a total of 22 courses without dose-limiting toxicity. Specific transgene expression was detected by reverse transcriptase polymerase chain reaction in bladder biopsy tissue from two of seven assessable patients. There were no changes in p53, p21waf1/cip1, or bax protein levels in bladder epithelium evident from immunohistochemical analysis of 11 assessable patients. Outpatient administration of multiple courses was feasible and well tolerated. A patient with advanced superficial bladder cancer showed evidence of tumor response. CONCLUSION: Intravesical instillation of Ad5CMV-p53 is safe, feasible, and biologically active when administered in multiple doses to patients with bladder cancer. Observations from this study indicate that this treatment has an antitumor effect in superficial transitional-cell carcinoma. Improvements in the efficiency of gene transfer and the levels of gene expression are required to develop more effective gene therapy for bladder cancer.