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1.
Breast Cancer Res ; 26(1): 8, 2024 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-38212792

RESUMO

BACKGROUND: To understand the dynamics that limit use of risk-management options by women at high risk of breast cancer, there is a critical need for research that focuses on patient perspectives. Prior research has left important gaps: exclusion of high-risk women not in risk-related clinical care, exclusion of non-white populations, and lack of attention to the decision-making processes that underlie risk-management choices. Our objective was to create a more inclusive dataset to facilitate research to address disparities related to decision making for breast cancer risk management. METHODS: The Daughter Sister Mother Project survey collects comprehensive information about the experiences of women at high risk of breast cancer. We collected novel measures of feelings about and reactions to cancer screenings; knowledge, barriers, and facilitators of risk-management options; beliefs related to cancer risk and risk management; and involvement with loved ones who had cancer. Eligible individuals were non-Hispanic white and non-Hispanic Black adult women who self-identified as having high risk of breast cancer and had no personal history of cancer. Between October 2018 and August 2019, 1053 respondents completed the online survey. Of these, 717 were confirmed through risk prediction modeling to have a lifetime breast cancer risk of ≥ 20%. Sociodemographic characteristics of this sample were compared to those of nationally representative samples of the US population: the 2019 Health Information National Trends Survey and the Pew Research Center report: Jewish Americans in 2020. RESULTS: The sample of 717 women at objectively high risk of breast cancer was largely (95%) recruited from non-clinical sources. Of these respondents, only 31% had seen a genetic counselor, 34% had had genetic testing specific to breast cancer risk, and 35% had seen at least one breast or cancer care specialist. The sample includes 35% Black respondents and 8% with Ashkenazi Jewish ancestry. Although encompassing a substantial range of ages, incomes, and education levels, respondents are overall somewhat younger, higher-income, and more educated than the US population as a whole. CONCLUSIONS: The DSM dataset offers comprehensive data from a community-based, diverse sample of women at high risk of breast cancer. The dataset includes substantial proportions of Black and Ashkenazi Jewish women and women who are not already in clinical care related to their breast cancer risk. This sample will facilitate future studies of risk-management behaviors among women who are and are not receiving high-risk care, and of variations in risk-management experiences across race and ethnicity.


Assuntos
Neoplasias da Mama , Adulto , Humanos , Feminino , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/genética , Mães , Núcleo Familiar , Inquéritos e Questionários , Gestão de Riscos
2.
Breast Cancer Res Treat ; 205(1): 61-73, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38280052

RESUMO

PURPOSE: Aromatase inhibitor (AI) therapy reduces risk of recurrence and death for postmenopausal women with breast cancer (BC); however, AI-induced arthralgia (AIIA) can lead to discontinuation of treatment. Curcumin, a bioactive polyphenolic substance, may help ameliorate inflammation-related conditions including osteoarthritis and pain. METHODS: We conducted a multisite randomized placebo-controlled, double-blind pilot trial (Alliance A22_Pilot9) to evaluate the effects of nanoemulsion curcumin (NEC, 200 mg/day) in postmenopausal women experiencing AIIA for ≥ 3 months. The primary objective was to determine the feasibility of using Functional Assessment of Cancer Treatment-Endocrine Symptoms (FACT-ES) to detect changes from 0 (T0) to 3 months (T3) of NEC treatment in AI-induced symptoms and well-being; secondary objectives included evaluation of changes in Disabilities of the Shoulder, Arm, and Hand (DASH), Brief Pain Inventory-short form (BPI-SF), grip strength, and biomarkers at T0 and T3. RESULTS: Forty-two patients were randomized to NEC or placebo; 34 women completed the 3-month study. Patient-reported outcome measures (PROMs: FACT-ES, DASH, BPI-SF) and biospecimens were collected at T0-T3 in > 80% of participants. Adherence was ≥ 90% for both arms. PROMs and grip strength did not differ significantly by treatment arm. Plasma curcumin was detected only in NEC arm participants. Serum estradiol and estrone levels were below detection or low on study agent. Gastrointestinal adverse effects were commonly reported in both arms. CONCLUSION: NEC versus placebo in a multisite randomized trial is feasible and well-tolerated. Additional studies with larger sample size are needed to further evaluate the efficacy and safety of NEC in treatment of AIIA. CLINICALTRIALS: gov Identifier: NCT03865992, first posted March 7, 2019.


Assuntos
Inibidores da Aromatase , Neoplasias da Mama , Curcumina , Humanos , Feminino , Curcumina/uso terapêutico , Curcumina/administração & dosagem , Inibidores da Aromatase/efeitos adversos , Inibidores da Aromatase/administração & dosagem , Projetos Piloto , Pessoa de Meia-Idade , Idoso , Neoplasias da Mama/tratamento farmacológico , Método Duplo-Cego , Emulsões , Resultado do Tratamento , Pós-Menopausa , Artralgia/induzido quimicamente , Artralgia/tratamento farmacológico
3.
Cancer ; 127(2): 300-309, 2021 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-33079393

RESUMO

BACKGROUND: Lymphedema is an adverse effect of breast cancer treatment that causes swelling and pain in the arm and hand. We tested 2 lymphedema prevention interventions and their impact on health-related quality of life (HRQOL) in a group-randomized trial at 38 cooperative group sites within the United States. METHODS: Patients were recruited before breast surgery. Sites were randomly assigned to education-only (EO) lymphedema prevention or education plus exercise and physical therapy (LEAP). Lymphedema was defined as a ≥10% difference in arm volume at any time from baseline to 18 months postsurgery. HRQOL was assessed using the Functional Assessment of Cancer Therapy-Breast plus 4 lymphedema items (FACT-B+4). Longitudinal mixed model regression analysis, adjusting for key demographic and clinical variables, examined participants' HRQOL by intervention group and lymphedema status. RESULTS: A total of 547 patients (56% LEAP) were enrolled and completed HRQOL assessments. The results revealed no differences between the interventions in preventing lymphedema (P = .37) or HRQOL (FACT-B+4 total score; P = .8777). At 18 months, the presence of lymphedema was associated with HRQOL at borderline significance (P = .0825). However, African American patients reported greater lymphedema symptoms (P = .0002) and better emotional functioning (P = .0335) than patients of other races or ethnicities. Lower HRQOL during the intervention was associated with younger age (P ≤ .0001), Eastern Cooperative Oncology Group performance status >0 (P = .0002), ≥1 positive lymph nodes (P = .0009), having no education beyond high school (P < .0001), having undergone chemotherapy (P = .0242), and having had only axillary node dissection or sentinel node biopsy versus both (P = .0007). CONCLUSION: The tested interventions did not differ in preventing lymphedema or in HRQOL outcomes. African American women reported greater HRQOL impacts due to lymphedema symptoms than women of other races or ethnicities.


Assuntos
Neoplasias da Mama/epidemiologia , Neoplasias da Mama/cirurgia , Linfedema/epidemiologia , Linfedema/prevenção & controle , Complicações Cognitivas Pós-Operatórias/epidemiologia , Complicações Cognitivas Pós-Operatórias/prevenção & controle , Qualidade de Vida , Adulto , Negro ou Afro-Americano , Idoso , Idoso de 80 Anos ou mais , Intervenção Médica Precoce/métodos , Terapia por Exercício/métodos , Feminino , Seguimentos , Humanos , Excisão de Linfonodo/efeitos adversos , Linfedema/etnologia , Mastectomia/efeitos adversos , Pessoa de Meia-Idade , Autorrelato , Biópsia de Linfonodo Sentinela , Estados Unidos/epidemiologia , Adulto Jovem
4.
Cancer ; 127(2): 291-299, 2021 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-33079411

RESUMO

BACKGROUND: Lymphedema affects many women who are treated for breast cancer. We examined the effectiveness of an education-only (EO) versus education plus sleeve compression/exercise intervention (lymphedema education and prevention [LEAP]) on lymphedema incidence and range of motion (ROM) in a group-randomized trial across 38 cooperative group sites. METHODS: The treating institution was randomly assigned to either EO or LEAP by a study statistician. All patients at a treating institution participated in the same intervention (EO or LEAP) to minimize contamination bias. Participants completed surveys, arm volume measurements, and self-reported ROM assessments before surgery and at 12 and 18 months after surgery. Lymphedema was defined as a ≥10% difference in limb volume at any time post-surgery up to 18 months after surgery or diagnosis by a health provider. Cochran-Mantel-Haenszel tests were used to compare lymphedema-free rates between groups, stratified by lymph node surgery type. Self-reported ROM differences were compared between groups. RESULTS: A total of 554 participants (56% LEAP) were included in the analyses. At 18 months, lymphedema-free rates were 58% (EO) versus 55% (LEAP) (P = .37). ROM for both arms was greater in LEAP versus EO at 12 months; by 18 months, most women reported full ROM, regardless of group. In LEAP, only one-third wore a sleeve ≥75% of the time; 50% performed lymphedema exercises at least weekly. CONCLUSION: Lymphedema incidence did not differ by intervention group at 18 months. Poor adherence in the LEAP group may have contributed. However, physical therapy may speed recovery of ROM. Further research is needed to effectively reduce the incidence and severity of lymphedema in patients who have breast cancer.


Assuntos
Neoplasias da Mama/cirurgia , Linfedema/epidemiologia , Linfedema/prevenção & controle , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/prevenção & controle , Adulto , Idoso , Idoso de 80 Anos ou mais , Braço/patologia , Intervenção Médica Precoce/métodos , Terapia por Exercício/métodos , Feminino , Seguimentos , Mãos/patologia , Humanos , Incidência , Excisão de Linfonodo/efeitos adversos , Excisão de Linfonodo/métodos , Mastectomia/efeitos adversos , Pessoa de Meia-Idade , Amplitude de Movimento Articular , Autorrelato , Resultado do Tratamento , Adulto Jovem
5.
Ann Surg Oncol ; 27(7): 2177-2187, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31965375

RESUMO

BACKGROUND AND PURPOSE: The Breast and Cervical Cancer Treatment Program (BCCTP) Act, passed by Congress in 2000, provides time-limited coverage to uninsured breast or cervical cancer patients. We examine survival differences between BCCTP cases and insured controls. METHODS: Stage I-III breast cancer patients, covered under California's BCCTP from 2005 to 2009 (N = 6343), were 1:1 matched with California Cancer Registry controls on age, race/ethnicity, and cancer stage. Overall and disease-specific (OS and DSS) survival were compared using multivariate regression. RESULTS: BCCTP cases were more often unmarried [odds ratio (OR) 2.47, 95% confidence interval (CI) 2.30-2.66], with poorly/undifferentiated tumors (OR 1.26, CI 1.13-1.40), classified as ER negative (OR 1.10, CI 1.02-1.20) and/or PR negative (OR 1.09, CI 1.01-1.17). Cases were more likely to undergo mastectomy (OR 1.13, CI 1.05-1.21) or no surgery (OR 1.64, CI 1.31-2.05) versus lumpectomy. Cases were also more likely to undergo radiation (OR 1.11, CI 1.03-1.19). Endocrine therapy rates were marginally lower in cases (OR 0.93, CI 0.86-1.00). OS and DSS were shorter in BCCTP cases on multivariate analysis (HR 1.29, CI 1.17-1.42 and HR 1.27, CI 1.14-1.42, respectively). When stratified by socioeconomic status (SES), cases had significantly shorter OS and DSS except in the lowest quintile. When stratified by stage, cases had significantly shorter OS and DSS, except for stage I. CONCLUSIONS: The BCCTP provides uninsured breast cancer patients with comprehensive and timely care. Although our results suggest that BCCTP delivers quality care, BCCTP patients have shorter survival rates, even after accounting for SES and stage differences. Further assistance to vulnerable populations is warranted, including longer duration of treatment coverage, and surveillance adhering to NCCN compliant surveillance programs.


Assuntos
Neoplasias da Mama , Cobertura do Seguro , Neoplasias do Colo do Útero , Neoplasias da Mama/economia , Neoplasias da Mama/mortalidade , Neoplasias da Mama/cirurgia , California/epidemiologia , Feminino , Humanos , Mastectomia , Análise de Sobrevida , Neoplasias do Colo do Útero/terapia
6.
Breast Cancer Res Treat ; 167(3): 709-718, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29101597

RESUMO

PURPOSE: Aromatase inhibitor (AI)-induced joint symptoms negatively impact drug adherence and quality of life in breast cancer survivors. Mechanisms underlying symptoms may include inflammation. It is hypothesized that n - 3 polyunsaturated fatty acids (PUFAs) have anti-inflammatory properties and may reduce symptoms. METHODS: We conducted a randomized, double-blind, placebo-controlled study comparing 4.3 g/day n - 3 PUFA supplements vs placebo for 24 weeks in postmenopausal breast cancer patients starting adjuvant AIs. Primary endpoints were adherence and tolerability; secondary outcomes included inflammatory cytokines and symptoms assessed by the Brief Pain Inventory short form (BPI-SF) and Functional Assessment of Cancer Treatment-Endocrine Symptoms (FACT-ES) at 0, 12, and 24 weeks. RESULTS: Forty-four women were randomized, of which 35 completed the study. Adherence was ≥ 88% based on these 35 patients with pill counts as well as change in red blood cell (RBC) n - 3 PUFAs. Common toxicities included grade 1 flatulence (55% of both groups) and belching (45% of n - 3 group). Mean pain severity scores (BPI-SF) did not change significantly by time or treatment arm. Quality of life, based on FACT-ES scores, significantly decreased within placebo (p = 0.04), but not the n - 3 group (p = 0.58), with a trend toward between-group differences (p = 0.06) at 12 weeks, but no significant differences at 24 weeks. RBC n - 3 levels were strongly positively correlated with FACT-ES at 12 weeks, but attenuated at 24 weeks. CONCLUSION: High-dose n - 3 PUFA supplementation is feasible and well tolerated when administered with AIs. Additional studies are needed to evaluate efficacy in prevention of joint symptoms.


Assuntos
Inibidores da Aromatase/efeitos adversos , Neoplasias da Mama/complicações , Ácidos Graxos Ômega-3/administração & dosagem , Dor Musculoesquelética/dietoterapia , Adulto , Idoso , Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Sobreviventes de Câncer , Suplementos Nutricionais , Método Duplo-Cego , Feminino , Humanos , Pessoa de Meia-Idade , Dor Musculoesquelética/induzido quimicamente , Dor Musculoesquelética/patologia , Estadiamento de Neoplasias , Projetos Piloto , Qualidade de Vida , Inquéritos e Questionários
7.
Proc Natl Acad Sci U S A ; 112(4): 1185-9, 2015 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-25583501

RESUMO

Animals with compact sensory systems face an encoding problem where a small number of sensory neurons are required to encode information about its surrounding complex environment. Using Caenorhabditis elegans worms as a model, we ask how chemical stimuli are encoded by a small and highly connected sensory system. We first generated a comprehensive library of transgenic worms where each animal expresses a genetically encoded calcium indicator in individual sensory neurons. This library includes the vast majority of the sensory system in C. elegans. Imaging from individual sensory neurons while subjecting the worms to various stimuli allowed us to compile a comprehensive functional map of the sensory system at single neuron resolution. The functional map reveals that despite the dense wiring, chemosensory neurons represent the environment using sparse codes. Moreover, although anatomically closely connected, chemo- and mechano-sensory neurons are functionally segregated. In addition, the code is hierarchical, where few neurons participate in encoding multiple cues, whereas other sensory neurons are stimulus specific. This encoding strategy may have evolved to mitigate the constraints of a compact sensory system.


Assuntos
Caenorhabditis elegans/fisiologia , Mecanotransdução Celular/fisiologia , Rede Nervosa/fisiologia , Células Receptoras Sensoriais/fisiologia , Animais , Animais Geneticamente Modificados/fisiologia , Caenorhabditis elegans/citologia , Cálcio/metabolismo , Rede Nervosa/citologia , Células Receptoras Sensoriais/citologia
8.
J Pediatr Nurs ; 42: 100-103, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29706299

RESUMO

PURPOSE: Administering oral medication to infants is challenging for caregivers, often resulting in incomplete delivery of the intended dose. Pacidose® is an oral medication delivery device that consists of a syringe attached to a tunneled pacifier. This study aimed to determine caregiver and nurse satisfaction and success rate of the Pacidose in the administration of acetaminophen to infants in the pediatric emergency department (ED). DESIGN AND METHODS: This was a prospective trial involving a convenience sample of patients who presented to a pediatric ED between November 2015 and August 2016. Patients younger than 24 months with a physician order for acetaminophen were eligible. Each child received a single dose of acetaminophen delivered by the Pacidose. Nurses, parents, and observing investigators were surveyed with a standardized questionnaire regarding the effectiveness, satisfaction and success rate of Pacidose. RESULTS: 61 patients were enrolled. The median age was 10 months and Pacidose was successful in 77% of patients. Those who required an alternative delivery route were older and no longer used pacifiers. Nurses reported that Pacidose helped administer the medication more easily in 66% of infants and 95% of parents preferred the Pacidose over standard delivery devices. CONCLUSIONS: Pacidose was well tolerated by infants, and both parents and nurses were highly satisfied with this method of administering acetaminophen. PRACTICE IMPLICATIONS: Pacidose is an easy to implement device that can help nurses with oral medication administration. It may have the greatest impact in younger children with recent pacifier use.


Assuntos
Acetaminofen/administração & dosagem , Anti-Inflamatórios não Esteroides/administração & dosagem , Serviço Hospitalar de Emergência , Chupetas/estatística & dados numéricos , Administração Oral , Feminino , Humanos , Lactente , Masculino , Satisfação do Paciente/estatística & dados numéricos , Enfermagem Pediátrica/métodos , Estudos Prospectivos , Comportamento de Sucção
9.
Breast Cancer Res ; 19(1): 34, 2017 03 24.
Artigo em Inglês | MEDLINE | ID: mdl-28340626

RESUMO

Several medical management approaches have been shown to be effective in preventing breast cancer and detecting it early among women at elevated risk: 1) prophylactic mastectomy; 2) prophylactic oophorectomy; 3) chemoprevention; and 4) enhanced screening routines. To varying extents, however, these approaches are substantially underused relative to clinical practice recommendations. This article reviews the existing research on the uptake of these prevention approaches, the characteristics of women who are likely to use various methods, and the decision-making processes that underlie the differing choices of women. It also highlights important areas for future research, detailing the types of studies that are particularly needed in four key areas: documenting women's perspectives on their own perceptions of risk and prevention decisions; explicit comparisons of available prevention pathways and their likely health effects; the psychological, interpersonal, and social processes of prevention decision making; and the dynamics of subgroup variation. Ultimately, this research could support the development of interventions that more fully empower women to make informed and values-consistent decisions, and to move towards favorable health outcomes.


Assuntos
Neoplasias da Mama/prevenção & controle , Neoplasias da Mama/psicologia , Tomada de Decisões , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/epidemiologia , Comportamento de Escolha , Detecção Precoce de Câncer/métodos , Feminino , Testes Genéticos/métodos , Humanos , Risco
10.
J Magn Reson Imaging ; 45(5): 1379-1384, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-27779802

RESUMO

PURPOSE: Previous studies of breast MR elastography (MRE) evaluated the technique at magnetic field strengths of 1.5 Tesla (T) with the breast in contact with the driver. The aim of this study is to evaluate breast stiffness measurements and their reproducibility using a soft sternal driver at 3T and compare the results with qualitative measures of breast density. MATERIALS AND METHODS: Twenty-two healthy volunteers each underwent two separate breast MRE scans in a 3T MRI. MRE vibrations were introduced into the breasts at 60 Hz using a soft sternal driver and axial slices were collected using a gradient echo MRE sequence. Mean stiffness measurements were calculated for each volunteer as well as a measure of reproducibility using concordance correlation between scans. Mean stiffness values for each volunteer were assessed and related to amounts of fibroglandular tissue (i.e., breast lobules, ducts, and fibrous connective tissue). RESULTS: The stiffness values were reproducible with a significant P-value < 0.0001 between two scans with concordance correlation of 0.87 and 0.91 for center slice and grouping all slices, respectively. Volunteers with dense breasts (i.e., higher grades of fibroglandular tissue) had mean stiffness values of 0.96 kPa (center slice) and 0.92 kPa (all slices) while those without dense breasts had mean stiffness values of 0.85 kPa (center slice) and 0.83 kPa (all slices) (P ≤ 0.05). CONCLUSION: Breast MRE is a reproducible technique at 3T using a soft sternal driver. Dense breasts had significantly higher stiffness measurements compared with nondense breasts. LEVEL OF EVIDENCE: 2 J. MAGN. RESON. IMAGING 2017;45:1379-1384.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Mama/diagnóstico por imagem , Técnicas de Imagem por Elasticidade/métodos , Imageamento por Ressonância Magnética , Algoritmos , Módulo de Elasticidade , Feminino , Voluntários Saudáveis , Humanos , Aumento da Imagem/métodos , Interpretação de Imagem Assistida por Computador/métodos , Processamento de Imagem Assistida por Computador , Reprodutibilidade dos Testes
11.
J Clin Microbiol ; 54(3): 768-70, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26699704

RESUMO

Listeriosis is a serious foodborne infection that disproportionately affects elderly adults, pregnant women, newborns, and immunocompromised individuals. Diagnosis is made by culturing Listeria monocytogenes from sterile body fluids or from products of conception. This report describes the investigations of two listeriosis pseudo-outbreaks caused by contaminated laboratory media made from sheep blood.


Assuntos
Surtos de Doenças , Listeria monocytogenes/genética , Listeriose/epidemiologia , Listeriose/transmissão , Meios de Cultura , Genoma Bacteriano , Humanos , Laboratórios , Listeria monocytogenes/classificação , Listeria monocytogenes/isolamento & purificação , Tipagem de Sequências Multilocus , Filogenia , Estados Unidos/epidemiologia
12.
Int J Cancer ; 137(12): 2934-46, 2015 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-26137879

RESUMO

There is increasing evidence that chronic inflammation is associated with increased breast cancer risk. Long-chain omega-3 polyunsaturated fatty acids (LCω-3PUFA) may reduce circulating biomarkers of inflammation; however associations of blood LCω-3PUFA with breast tissue LCω-3PUFA and breast tissue biomarkers of inflammation are not well understood. We conducted a cross-sectional analysis of breast tissue and blood samples from n = 85 women with no history of breast cancer, who underwent breast reduction surgery. Fatty acids of erythrocytes and undissected breast tissues were analyzed by gas chromatography; C-reactive protein (CRP), interleukin (IL)-6 and IL-8 in plasma and tissue were measured by ELISA. Multivariable-adjusted regression models were used to estimate associations between erythrocyte LCω-3PUFA and breast tissue biomarkers. Women in the highest erythrocyte LCω-3PUFA tertile had LCω-3PUFA concentrations in the breast 73% (95% CI: 31-128%; p trend < 0.0001) higher than women in the lowest tertile. Associations for each individual LCω-3PUFA were similar in magnitude. No significant association was found for the shorter ω-3 PUFA, α-linolenic acid. Although compatible with no association, women in the highest tertile of erythrocyte eicosapentaenoic acid had a nonsignificant 32% (95% CI: -23 to 62%) reduced breast tissue CRP. No correlation was observed between erythrocyte ω-3 PUFA and tissue IL-6 or IL-8 concentrations. Our findings provide evidence that erythrocyte ω-3 fatty acids are valid measures of breast tissue concentrations, and limited evidence that inverse associations from prospective epidemiologic studies of blood LCω-3PUFA and breast cancer risk may be partly explained by reductions in breast tissue inflammation; however, these findings require replication.


Assuntos
Eritrócitos/metabolismo , Ácidos Graxos Ômega-3/metabolismo , Ácidos Graxos Ômega-6/metabolismo , Glândulas Mamárias Humanas/metabolismo , Adulto , Idoso , Biomarcadores/metabolismo , Estudos Transversais , Feminino , Humanos , Mediadores da Inflamação/metabolismo , Mamoplastia , Glândulas Mamárias Humanas/cirurgia , Pessoa de Meia-Idade , Estudos Prospectivos
13.
Exp Mol Pathol ; 98(3): 439-45, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25839092

RESUMO

Repetitive elements (REs) make up the vast majority of the mammalian genomes. We identified species-specific genomic libraries of RE arrays. The non-random configurations of RE arrays suggest their functions. We tested whether RE arrays undergo age- and tissue/cell-specific rearrangements. An RE array of C57BL/6J mice, containing tandem repeats of a mosaic of transposable REs, was selected to examine rearrangements in different ages and tissues. There were marked changes in the array configuration in the genomes of the skin and brain in all mice of six weeks and older, whereas the heart and liver had alterations at 29weeks. The temporal variations were confirmed by identifying putative rearrangement junctions. Temporal and spatial rearrangements of certain RE arrays may contribute to the acquired characteristics of the genome information system.


Assuntos
Encéfalo/metabolismo , Genoma , Sequências Repetitivas de Ácido Nucleico , Pele/metabolismo , Animais , Sequência de Bases , Encéfalo/crescimento & desenvolvimento , Camundongos , Camundongos Endogâmicos C57BL , Dados de Sequência Molecular , Especificidade de Órgãos , Polimorfismo Genético , Pele/crescimento & desenvolvimento , Especificidade da Espécie
14.
Nature ; 461(7267): 1084-91, 2009 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-19847259

RESUMO

The tumour stroma is believed to contribute to some of the most malignant characteristics of epithelial tumours. However, signalling between stromal and tumour cells is complex and remains poorly understood. Here we show that the genetic inactivation of Pten in stromal fibroblasts of mouse mammary glands accelerated the initiation, progression and malignant transformation of mammary epithelial tumours. This was associated with the massive remodelling of the extracellular matrix (ECM), innate immune cell infiltration and increased angiogenesis. Loss of Pten in stromal fibroblasts led to increased expression, phosphorylation (T72) and recruitment of Ets2 to target promoters known to be involved in these processes. Remarkably, Ets2 inactivation in Pten stroma-deleted tumours ameliorated disruption of the tumour microenvironment and was sufficient to decrease tumour growth and progression. Global gene expression profiling of mammary stromal cells identified a Pten-specific signature that was highly represented in the tumour stroma of patients with breast cancer. These findings identify the Pten-Ets2 axis as a critical stroma-specific signalling pathway that suppresses mammary epithelial tumours.


Assuntos
Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Fibroblastos/metabolismo , Neoplasias Epiteliais e Glandulares/metabolismo , Neoplasias Epiteliais e Glandulares/patologia , PTEN Fosfo-Hidrolase/metabolismo , Células Estromais/metabolismo , Animais , Linhagem Celular Tumoral , Proliferação de Células , Transformação Celular Neoplásica , Matriz Extracelular/metabolismo , Deleção de Genes , Regulação Neoplásica da Expressão Gênica , Humanos , Imunidade Inata , Neoplasias Mamárias Experimentais/metabolismo , Neoplasias Mamárias Experimentais/patologia , Camundongos , Camundongos Transgênicos , PTEN Fosfo-Hidrolase/deficiência , PTEN Fosfo-Hidrolase/genética , Proteína Proto-Oncogênica c-ets-2/deficiência , Proteína Proto-Oncogênica c-ets-2/metabolismo
15.
Brain Behav Immun ; 41: 232-8, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24945717

RESUMO

Attachment theory provides a framework for understanding individual differences in chronic interpersonal stress. Attachment anxiety, a type of relationship insecurity characterized by worry about rejection and abandonment, is a chronic interpersonal stressor. Stress impacts cellular immunity, including herpesvirus reactivation. We investigated whether attachment anxiety was related to the expression of a latent herpesvirus, Epstein-Barr virus (EBV), when individuals were being tested for breast or colon cancer and approximately 1 year later. Participants (N=183) completed a standard attachment questionnaire and provided blood to assess EBV viral capsid antigen (VCA) IgG antibody titers. Individuals with more attachment anxiety had higher EBV VCA IgG antibody titers than those with less attachment anxiety. The strength of the association between attachment anxiety and antibody titers was the same at both assessments. This study is the first to show an association between latent herpesvirus reactivation and attachment anxiety. Because elevated herpesvirus antibody titers reflect poorer cellular immune system control over the latent virus, these data suggest that high attachment anxiety is associated with cellular immune dysregulation.


Assuntos
Transtornos de Ansiedade/imunologia , Neoplasias da Mama/imunologia , Neoplasias da Mama/psicologia , Neoplasias do Colo/imunologia , Neoplasias do Colo/psicologia , Herpesvirus Humano 4/fisiologia , Apego ao Objeto , Ativação Viral , Latência Viral/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Antígenos Virais/imunologia , Transtornos de Ansiedade/etiologia , Transtornos de Ansiedade/virologia , Neoplasias da Mama/virologia , Proteínas do Capsídeo/imunologia , Neoplasias do Colo/virologia , Comorbidade , Depressão/etiologia , Depressão/imunologia , Depressão/virologia , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Relações Interpessoais , Masculino , Pessoa de Meia-Idade , Distúrbios do Início e da Manutenção do Sono/imunologia , Distúrbios do Início e da Manutenção do Sono/virologia , Apoio Social , Fatores Socioeconômicos , Estresse Fisiológico , Estresse Psicológico/etiologia , Estresse Psicológico/imunologia , Estresse Psicológico/virologia , Inquéritos e Questionários , Ativação Viral/imunologia
16.
Psychooncology ; 23(12): 1356-64, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24729533

RESUMO

BACKGROUND: Cancer survivors often experience cognitive difficulties after treatment completion. Although chemotherapy enhances risk for cognitive problems, it is likely only one piece of a complex puzzle that explains survivors' cognitive functioning. Loneliness may be one psychosocial risk factor. The current studies included both subjective and objective cognitive measures and tested whether lonelier breast cancer survivors would have more concentration and memory complaints and experience more concentration difficulties than their less lonely counterparts. METHODS: The relationship between loneliness and cognitive function was tested among three samples of breast cancer survivors. Study 1 was a sample of breast cancer survivors (n = 200) who reported their concentration and memory problems. Study 2a was a sample of breast cancer survivors (n = 185) and noncancer controls (n = 93) who reported their concentration and memory problems. Study 2b was a subsample of Study 2a breast cancer survivors (n = 22) and noncancer controls (n = 21) who completed a standardized neuropsychological test assessing concentration. RESULTS: Studies 1 and 2a revealed that lonelier women reported more concentration and memory problems than less lonely women. Study 2b utilized a standardized neuropsychological continuous performance test and demonstrated that lonelier women experienced more concentration problems than their less lonely counterparts. CONCLUSIONS: These studies demonstrated that loneliness is linked to concentration and memory complaints and the experience of concentration problems among breast cancer survivors. The results were also highly consistent across three samples of breast cancer survivors. These data suggest that loneliness may be a risk factor for cognitive difficulties among cancer survivors.


Assuntos
Neoplasias da Mama/psicologia , Transtornos Cognitivos/psicologia , Solidão/psicologia , Sobreviventes/psicologia , Adulto , Idoso , Atenção , Estudos de Casos e Controles , Feminino , Humanos , Memória , Pessoa de Meia-Idade , Testes Neuropsicológicos , Fatores de Risco
17.
Psychooncology ; 22(8): 1889-94, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23255459

RESUMO

OBJECTIVE: A cancer diagnosis provokes significant levels of emotional distress, with intrusive thoughts being the most common manifestation among breast cancer survivors. Cancer-related intrusive thoughts can take the form of emotional memories, flashbacks, nightmares, and intrusive images. Emotional arousal after a severe life stressor prolongs adrenergic activation, which in turn may increase risk for post-traumatic symptomatology. However, antihypertensive beta-blockers block adrenergic activation and are known to reduce traumatic memories and related psychological distress. Thus, the current study examined the association between beta-blocker use and the severity of cancer-related intrusive thoughts and related symptoms following a cancer diagnosis. METHODS: The 174 breast and 36 female colorectal cancer patients who had recently undergone diagnostic screening or biopsy included 39 beta-blocker users and 171 non-users. Prior to any cancer treatment including surgery, participants completed questionnaires that included the Impact of Events Scale and the Center for Epidemiological Studies Depression Scale. Analyses controlled for age, education, cancer stage, cancer type, days since diagnosis, marital status, depression, and comorbidities. RESULTS: Although the high rates of cancer-related distress in this sample were similar to those of other studies with recently diagnosed patients, beta-blocker users endorsed 32% fewer cancer-related intrusive thoughts than non-users. CONCLUSIONS: Recently diagnosed cancer patients using beta-blockers reported less cancer-related psychological distress. These results suggest that beta-blocker use may benefit cancer patients' psychological adjustment following diagnosis, and provide a promising direction for future investigations on the pharmacological benefits of beta-blockers for cancer-related distress.


Assuntos
Antagonistas Adrenérgicos beta/administração & dosagem , Neoplasias da Mama/diagnóstico , Neoplasias Colorretais/diagnóstico , Transtornos de Estresse Pós-Traumáticos/psicologia , Pensamento/efeitos dos fármacos , Adaptação Psicológica , Adulto , Idoso , Idoso de 80 Anos ou mais , Ansiedade/etiologia , Ansiedade/psicologia , Neoplasias da Mama/psicologia , Neoplasias Colorretais/psicologia , Depressão/etiologia , Depressão/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Ohio , Escalas de Graduação Psiquiátrica , Estresse Psicológico , Inquéritos e Questionários
18.
PLoS One ; 18(3): e0278742, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36857397

RESUMO

PURPOSE: Women at high risk of breast cancer face complex decisions about how to manage those risks. Substantial gaps in current knowledge include how women make these decisions and how decision making may differ across sub-populations. Among these critical gaps are the questions of (a) whether racial differences exist between the experiences of high-risk women navigating breast cancer risk, and (b) what consequences those racial differences might have on women's ability to manage their cancer risks. The present study is designed to address these questions directly. METHODS: Fifty semi-structured interviews were conducted with high-risk Black (n = 20) and white women (n = 30) between May 2015 and March 2016 in person in Ohio and by phone. Transcribed data were analyzed using grounded theory methods. MAIN FINDINGS: Our analyses suggest that many of the core decision-making dynamics high-risk women navigate differ by race. The experiences of white and Black women in our study differ in terms of (a) contextualizing risk-how women make sense of their own breast cancer risk, the degree to which they worry about risk, and how they prioritize risk within the contexts of their broader lives; (b) conceptualizing risk management-how, how much, and from whom women learn about and conceptualize their options for preventing cancer and/or ensuring that cancer gets diagnosed early; and (c) constraints-the external barriers women face throughout their decision-making and risk-management processes. In sum, the Black women we interviewed reported feeling less well-situated to consider and cope actively with breast cancer risk, less well-informed about risk-management options, and more constrained in their use of these options. CONCLUSIONS: High-risk women's accounts of the complex dynamics that shape breast cancer prevention decisions suggest that these dynamics vary substantially by race, such that Black women may experience disadvantages relative to whites.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Fatores Raciais , Mama , Pesquisa Qualitativa , Tomada de Decisões
19.
JCO Glob Oncol ; 9: e2300137, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37972329

RESUMO

PURPOSE: The aim of this study was to explore breast cancer (BC) challenges to identify opportunities for advocacy in southern Ethiopia in 2022. METHODS: Twenty-five participants from four local districts (kebeles) in Hawassa City were selected as key contributors to future work. Semistructured in-depth interviews were held for two clinicians, two local health bureau managers, two media managers, and three religious leaders. Two focus group discussions were conducted: one included six BC survivors and a caregiver; the other included two health extension workers, three members of the Women's Development Group, two community volunteers, one kebele leader, and one traditional healer. RESULTS: To our knowledge, our study was the first time that most participants had assembled. Many referred to patients as victims and BC as a killer disease or curse. Community and religious leaders were concerned about challenges and willing to collaborate. Survivors, providers, and religious leaders were identified as key sources of information, positive messages, and leadership. CONCLUSION: Recommendations for advocacy work in Hawassa include lobbying for BC as a health priority; including BC within the health extension package; initiating programs for earlier detection; educating the community to remove stigmas of the disease and treatments; working with media to disseminate messages that are inclusive of people in remote areas and speaking different languages; improving availability, affordability, and access to care; and assisting patients with psychosocial support. A strategic collaboration between religious leaders and health care providers was identified to increase community awareness and support advocacy for patients.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/terapia , Etiópia , Pesquisa Qualitativa , Agentes Comunitários de Saúde , População Rural
20.
Brain Behav Immun ; 26(3): 394-400, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21988771

RESUMO

Fatigue is a notable clinical problem in cancer survivors, and understanding its pathophysiology is important. The current study sought to determine biomarkers of fatigue that exist before cancer treatment. Relationships between the expression of latent Epstein-Barr virus (EBV) and cytomegalovirus (CMV) and fatigue were examined in 158 women newly diagnosed with breast cancer or awaiting a positive diagnostic result. Higher CMV antibody titers, but not EBV antibody titers, were associated with a greater likelihood of being fatigued. Associations between fatigue and higher CMV antibody titers remained after controlling for alcohol use, smoking, comorbidities, depressive symptoms, age, BMI, cancer stage, and sleep problems. More sleep problems and higher levels of depressive symptoms were also associated with a greater likelihood of being fatigued. CMV antibody titers, but not EBV antibody titers, were associated with higher levels of C-reactive protein (CRP), but CRP was not associated with fatigue. When the cellular immune system is compromised, reactivation of latent herpesviruses may fuel chronic inflammatory responses. Prior work has suggested that fatigue may be related to inflammation and its associated sickness behaviors; accordingly, our findings may be tapping into this same physiological substrate.


Assuntos
Neoplasias da Mama/complicações , Infecções por Citomegalovirus/complicações , Citomegalovirus/imunologia , Infecções por Vírus Epstein-Barr/complicações , Fadiga/complicações , Fadiga/virologia , Herpesvirus Humano 4/imunologia , Adulto , Idoso , Anticorpos Antivirais/análise , Proteína C-Reativa/análise , Depressão , Feminino , Humanos , Pessoa de Meia-Idade , Distúrbios do Início e da Manutenção do Sono
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