Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 82
Filtrar
1.
Can Oncol Nurs J ; 32(1): 38-48, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35280065

RESUMO

Objective: Cancer-related cognitive impairments experienced by cancer survivors cause many to seek non-pharmacological intereventions to manage these symptoms. The aim of this systematic review was to evaluate the effects of one such intervention, mindbody exercise (MBE), on cognitive function in cancer survivors. Design: Searches for relevant studies were conducted in four electronic databases, including PubMed, Embase, Scopus, and Web of Science. The Joanna Briggs Institute and Jadad scales were utilized to evaluate the quality of the selected studies. Results: Eleven studies including 1,032 participants, published between 2006 and 2019, were selected for review based on specific inclusion criteria. Our results indicated that interventions including, yoga, tai chi, and qigong may improve objective and subjective cognitive function in cancer survivors. Conclusion: Cancer survivors experiencing cognitive symptoms may benefit from participation in MBE. Adequately powered randomized controlled trials are required to establish the short- and long-term effects of MBE on cognitive functioning.

2.
J Cancer Educ ; 36(6): 1230-1236, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-32367183

RESUMO

Strengthening communication between providers and patients, especially those with cognitive impairment, is required given care complexity and fragmentation across the care continuum. Therefore, determining patient perceptions about the Siebens Health Care Notebook (SHCN), a tool to support self-management and strengthen communication and care continuity, is fundamental to understanding SHCN usability. Participants were breast cancer survivors in a study evaluating a 6-week cognitive rehabilitation program, who reported cancer-related cognitive impairment (Functional Assessment of Cancer Therapy-Cognitive Function-Perceived Cognitive Impairment (PCI) subscale < 59). Participant groups were alternately assigned to receive the SHCN (intervention) or not (control). SHCN recipients completed a 3-item qualitative perception survey at program completion. Both groups were surveyed at baseline, program completion, and 4 weeks later about communication with physicians. Scores were compared using Wilcoxon rank-sum tests. No baseline demographic or PCI score differences occurred between intervention (n = 29) and control (n = 16) groups. Of 22 (76%) who completed the SHCN perception survey, 100% endorsed it as useful in tracking health information, as helpful, and would recommend it to others. No group differences in communication activities with physicians were demonstrated. Women reporting cognitive impairment after breast cancer treatment perceived the SHCN as a beneficial self-care tool and would suggest it to others. Communication activities with physicians did not change during the study's short duration. Future research is needed to evaluate SHCN features contributing to helpfulness and details on use, including two-way communication activities between patients and physicians, across the care continuum.


Assuntos
Neoplasias da Mama , Sobreviventes de Câncer , Disfunção Cognitiva , Neoplasias da Mama/terapia , Atenção à Saúde , Feminino , Humanos , Sobreviventes
3.
Arch Phys Med Rehabil ; 101(6): 948-959, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32179067

RESUMO

OBJECTIVE: To quantify the effect of a psychoeducation-based cognitive rehabilitation intervention on breast cancer survivors' self-report of cognitive function and investigate the feasibility of accrual, adherence, and multisite program delivery using secure telehealth conferencing. DESIGN: Prospective, nonblinded, wait-list controlled pilot study. SETTING: Nonprofit academic medical center and university medical center with associated community practice affiliates. PARTICIPANTS: Adult female survivors of stage I-III breast cancer reporting cognitive complaints 2 months to 5 years after chemotherapy (N=61). Ongoing endocrine and/or anti-HER-2 therapy was allowed. Patients were excluded for history of other conditions involving impaired cognitive function. Combination referred and volunteered sample. In total, 107 women were screened, 61 consented, and 52 analyzed. No attrition due to adverse events. Group allocation was based on consent timing and next scheduled cohort to minimize wait time for wait-list controls. INTERVENTION: Psychoeducation-based cognitive rehabilitation intervention delivered in a group setting during 6 weekly 2.5-hour classes. Included presentation, class exercises, discussion, and homework exercises. Provided in-person and virtually by Health Insurance Portability and Accountability Act compliant and encrypted telehealth conferencing. MAIN OUTCOME MEASURES: Primary: self-report of perceived cognitive function (PCF) was compared between the intervention group (n=27) and wait-list controls (n=28) with the Functional Assessment of Cancer Therapy-Cognition perceived cognitive impairment subscale. Secondary: feasibility for multisite delivery via teleconferencing was measured by total accrual, percent adherence to 4 of the 6 weeks of content, and participant satisfaction ratings. RESULTS: The intervention group demonstrated improvement in PCF both at the conclusion of the intervention and 1 month later (P<.01). Within-group improvement in PCF was maintained at 6 and 12 months (P<.01). CONCLUSION: These study results provide further preliminary evidence of the efficacy of psychoeducation-based cognitive rehabilitation as an intervention for decreased PCF in breast cancer survivors with cognitive complaints after chemotherapy. Feasibility for accrual, adherence, and participant satisfaction with secure telehealth conferencing was demonstrated. These positive pilot study results will inform future work.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/psicologia , Sobreviventes de Câncer/psicologia , Transtornos Cognitivos/reabilitação , Telemedicina , Feminino , Humanos , Kansas , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos , Autorrelato
4.
BMC Med Res Methodol ; 19(1): 119, 2019 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-31185918

RESUMO

BACKGROUND: The Fred Hutchinson Cancer Research Center has engaged an External Stakeholder Advisory Group (ESAG) in the planning and implementation of the TrACER Study (S1415CD), a five-year pragmatic clinical trial assessing the effectiveness of a guideline-based colony stimulating factor standing order intervention. The trial is being conducted by SWOG through the National Cancer Institute Community Oncology Research Program in 45 clinics. The ESAG includes ten patient partners, two payers, two pharmacists, two guideline experts, four providers and one medical ethicist. This manuscript describes the ESAG's role and impact on the trial. METHODS: During early trial development, the research team assembled the ESAG to inform plans for each phase of the trial. ESAG members provide feedback and engage in problem solving to improve trial implementation. Each year, members participate in one in-person meeting, web conferences and targeted email discussion. Additionally, they complete a survey that assesses their satisfaction with communication and collaboration. The research team collected and reviewed stakeholder input from 2014 to 2018 for impact on the trial. RESULTS: The ESAG has informed trial design, implementation and dissemination planning. The group advised the trial's endpoints, regimen list and development of cohort and usual care arms. Based on ESAG input, the research team enhanced patient surveys and added pharmacy-related questions to the component application to assess order entry systems. ESAG patient partners collaborated with the research team to develop a patient brochure and study summary for clinic staff. In addition to identifying recruitment strategies and patient-oriented platforms for publicly sharing results, ESAG members participated as co-authors on this manuscript and a conference poster presentation highlighting stakeholder influence on the trial. The annual satisfaction survey results suggest that ESAG members were satisfied with the methods, frequency and target areas of their engagement in the trial during project years 1-3. CONCLUSIONS: Diverse stakeholder engagement has been essential in optimizing the design, implementation and planned dissemination of the TrACER Study. The lessons described in the manuscript may assist others to effectively partner with stakeholders on clinical research.


Assuntos
Ensaios Clínicos como Assunto/métodos , Neoplasias/terapia , Avaliação de Resultados da Assistência ao Paciente , Participação dos Interessados , Consultores , Humanos , Participação do Paciente
5.
Support Care Cancer ; 27(3): 1121-1128, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30097791

RESUMO

PURPOSE: The purpose of this cross-sectional comparative pilot study was to evaluate cognitive effort, indexed by pupillary response (PR), for breast cancer survivors (BCS) with complaints of cognitive dysfunction following chemotherapy. STUDY AIMS: Compare the cognitive effort employed by BCS to healthy controls (HC) during neuropsychological tests (NPT) for memory, sustained attention, verbal fluency, visuospatial ability, processing speed and executive function; and Investigate the relationship between PR-indexed cognitive effort and participants' self-report of cognitive function. METHODS: Self-report of cognitive function was collected from 23 BCS and 23 HC. PR was measured during NPT. Independent two-sample t tests or Wilcoxon rank sum tests were used to compare group scores. Between-group effect size (Cohen's d) was calculated for each outcome. Correlation between mean self-report scores and PR values, as well as 95% confidence intervals, was calculated. RESULTS: No group differences were demonstrated for NPT performance. BCS reported more issues with cognitive function than HC (p < .0001). A group effect for BCS was seen with PR-indexed cognitive effort for components of most NPT (p < .05). PR was correlated with most self-report measures of cognitive function (r = 0.33-0.45). CONCLUSIONS: PR sensitivity to cognitive effort across a variety of NPT and correlation with self-report of cognitive function was demonstrated. The portability, affordability, and "real-time" aspects of PR are attractive for potential use in the clinic setting to assess cognitive function. A larger study is needed to confirm these results. Prospective investigation of PR in BCS is needed to demonstrate sensitivity to cognitive function changes over time.


Assuntos
Sobreviventes de Câncer/psicologia , Cognição/fisiologia , Disfunção Cognitiva/fisiopatologia , Testes Neuropsicológicos , Pupila/fisiologia , Adulto , Antineoplásicos/efeitos adversos , Atenção , Neoplasias da Mama/tratamento farmacológico , Estudos de Casos e Controles , Transtornos Cognitivos/psicologia , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/psicologia , Estudos Transversais , Feminino , Humanos , Memória , Pessoa de Meia-Idade , Projetos Piloto , Autorrelato , Sobreviventes/psicologia
6.
Support Care Cancer ; 27(4): 1395-1403, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30128855

RESUMO

PURPOSE: The purpose of this pilot study was to evaluate the feasibility of an 8-week Qigong intervention to improve objectively and subjectively assessed cognitive function in breast cancer survivors who were 2 months to 8 years post completion of chemotherapy and radiation therapy. METHODS: A randomized, single-blind, three-arm intervention pilot was conducted to compare Qigong to gentle exercise and survivorship support. Feasibility was measured by recruitment, group session attendance, and adherence to home practice for the two exercise groups. Changes in self-report and objectively measured cognitive function were compared between the three groups from baseline (T1) to completion of the intervention (T2) and 4 weeks post intervention (T3). RESULTS: Fifty participants consented (83% of desired sample) with an overall attrition rate of 28%. Attrition was highest for the gentle exercise group (50%). Group attendance adherence ranged from 44 to 67%. The a priori established rate of 75% weekly attendance was not achieved, nor was the goal of 75% adherence to home practice for the two exercise groups (7 to 41%). Self-report of cognitive function improved most for the Qigong group (p = .01). Improvement was demonstrated for the Trail Making A (gentle exercise, p = .007) and F-A-S verbal fluency (support group, p = .02) tests. Qigong participants reported the most reduction of distress (p = .02). CONCLUSIONS: The study results suggest that mindfulness-based exercise may be superior to gentle exercise alone or survivorship support for improving self-report of cognitive function and distress after treatment for breast cancer. The mindfulness component may enhance the positive impact of exercise on cognitive function.


Assuntos
Neoplasias da Mama/psicologia , Sobreviventes de Câncer/psicologia , Transtornos Cognitivos/fisiopatologia , Cognição , Qigong , Adulto , Idoso , Neoplasias da Mama/fisiopatologia , Neoplasias da Mama/reabilitação , Transtornos Cognitivos/reabilitação , Feminino , Humanos , Pessoa de Meia-Idade , Projetos Piloto , Qualidade de Vida , Resultado do Tratamento
7.
Res Nurs Health ; 42(5): 324-333, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31389621

RESUMO

Androgen deprivation therapy (ADT) is a treatment used across the prostate cancer disease spectrum and works by suppressing testicular androgen production to castrate levels. Although ADT can provide survival benefits, it is also associated with increased risk for cardiovascular disease, metabolic syndrome, increased visceral fat mass, dyslipidemia, decreased arterial compliance, and diminished health-related quality of life. The Staying Strong And Healthy protocol is a telephone-delivered intervention led by a nurse coordinator to minimize the increased cardiovascular and metabolic risks associated with ADT. This study will evaluate the feasibility of the protocol and provides the foundation for future behavioral interventions across diverse populations of men on ADT.


Assuntos
Antagonistas de Androgênios/efeitos adversos , Antagonistas de Androgênios/uso terapêutico , Doenças Cardiovasculares/induzido quimicamente , Doenças Cardiovasculares/prevenção & controle , Neoplasias da Próstata/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Terapia Comportamental/métodos , Dieta Saudável/métodos , Terapia por Exercício/métodos , Estudos de Viabilidade , Estilo de Vida Saudável , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Qualidade de Vida , Telemedicina/métodos , Estados Unidos
8.
Support Care Cancer ; 26(2): 575-583, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28849337

RESUMO

PURPOSE: The purpose of the study was to prospectively examine changes in subjective and objective cognitive functions and quality of life (QOL) for pre- and peri-menopausal women receiving chemotherapy for breast cancer and to explore potential predictors of cognitive changes. METHODS: Participants were assessed as follows: prior to chemotherapy (T1), after cycle 3 (T2), within 2-3 weeks of completing adjuvant chemotherapy (T3) (N = 20), and 8+ years later (T4; n = 18). Objective cognitive function was measured with the High Sensitivity Cognitive Screen (T1, T3, T4). Subjective measures for cognitive function, depressive symptoms, fatigue, and mental and physical QOL were assessed at all time points. Estradiol levels were measured at T1, T2, and T3. The Functional Assessment of Cancer Therapy-Cognition and the MD Anderson Cancer Symptom Inventory item for neuropathy were administered at T4. RESULTS: No significant changes in objective cognitive function were found. However, participants reported decreased cognitive function over the course of treatment accompanied by depressive symptoms and fatigue. Depression and fatigue returned to near-baseline levels at T4, but over half of the participants continued to report mild to moderate depression. Estradiol levels were not associated with cognitive function. Neuropathy and higher body mass index (BMI) were associated with persistent cognitive complaints at T4 (adjusted R 2 = 0.712, p = 0.001). Higher QOL was correlated with better subjective cognitive function (r = 0.705, p = 0.002) and lower body mass index (r = - 0.502, p = 0.017) at T4. CONCLUSIONS: Further investigation of BMI, neuropathy, and depressive symptoms as predictors of persistent cognitive dysfunction following chemotherapy for breast cancer is warranted.


Assuntos
Neoplasias da Mama/psicologia , Quimioterapia Adjuvante/psicologia , Transtornos Cognitivos/psicologia , Qualidade de Vida/psicologia , Adulto , Neoplasias da Mama/patologia , Estudos Transversais , Feminino , Humanos , Estudos Longitudinais
9.
J Proteome Res ; 16(11): 4227-4236, 2017 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-28902521

RESUMO

Determining the effect of chemotherapeutic treatment on changes in protein expression can provide important targets for overcoming resistance. Due to challenges in simultaneously measuring large numbers of proteins, a paucity of data exists on global changes. To overcome these challenges, we utilized microwestern arrays that allowed us to measure the abundance and modification state of hundreds of cell signaling and transcription factor proteins in cells following drug exposure. HapMap lymphoblastoid cell lines (LCLs) were exposed to cisplatin, a chemotherapeutic agent commonly used to treat testicular, head and neck, non-small cell lung, and gynecological cancers. We evaluated the expression of 259 proteins following 2, 6, and 12 h of cisplatin treatment in two LCLs with discordant sensitivity to cisplatin. Of these 259 proteins, 66 displayed significantly different protein expression changes (p < 0.05). Fifteen of these proteins were evaluated in a second pair of LCLs with discordant sensitivities to cisplatin; six demonstrated significant differences in expression. We then evaluated a subset of 63 proteins in a second set of LCLs with discordant sensitivity, and 40% of those that were significant in the first pair were also significant in the second part with concordant directionality (p < 0.05). We functionally validated one of the top proteins identified, PDK1, and demonstrated a synergistic relationship between cisplatin and a PDK1 inhibitor in multiple lung cancer lines. This study highlights the potential for identifying novel targets through an understanding of cellular changes in protein expression and modification following drug treatments.


Assuntos
Cisplatino/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Proteômica/métodos , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Sinergismo Farmacológico , Humanos , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Piruvato Desidrogenase Quinase de Transferência de Acetil
10.
Am J Hum Genet ; 95(2): 194-208, 2014 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-25087611

RESUMO

Many genetic variants associated with human disease have been found to be associated with alterations in mRNA expression. Although it is commonly assumed that mRNA expression changes will lead to consequent changes in protein levels, methodological challenges have limited our ability to test the degree to which this assumption holds true. Here, we further developed the micro-western array approach and globally examined relationships between human genetic variation and cellular protein levels. We collected more than 250,000 protein level measurements comprising 441 transcription factor and signaling protein isoforms across 68 Yoruba (YRI) HapMap lymphoblastoid cell lines (LCLs) and identified 12 cis and 160 trans protein level QTLs (pQTLs) at a false discovery rate (FDR) of 20%. Whereas up to two thirds of cis mRNA expression QTLs (eQTLs) were also pQTLs, many pQTLs were not associated with mRNA expression. Notably, we replicated and functionally validated a trans pQTL relationship between the KARS lysyl-tRNA synthetase locus and levels of the DIDO1 protein. This study demonstrates proof of concept in applying an antibody-based microarray approach to iteratively measure the levels of human proteins and relate these levels to human genome variation and other genomic data sets. Our results suggest that protein-based mechanisms might functionally buffer genetic alterations that influence mRNA expression levels and that pQTLs might contribute phenotypic diversity to a human population independently of influences on mRNA expression.


Assuntos
Proteínas/metabolismo , Proteoma/genética , Locos de Características Quantitativas/genética , Transdução de Sinais/genética , Fatores de Transcrição/genética , Anticorpos/genética , Anticorpos/imunologia , Sequência de Bases , Linhagem Celular , Mapeamento Cromossômico , Proteínas de Ligação a DNA/biossíntese , Proteínas de Ligação a DNA/genética , Expressão Gênica , Variação Genética , Genoma Humano/genética , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Modelos Genéticos , Análise Serial de Proteínas , Proteínas/genética , Interferência de RNA , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , RNA Interferente Pequeno , Análise de Sequência de DNA , Transcriptoma/genética
11.
Psychooncology ; 26(1): 44-52, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-26486371

RESUMO

OBJECTIVE: In a sample of 368 postmenopausal women, we (1) determined within-cohort and between-cohort relationships between adjuvant systemic therapy for breast cancer and self-reported cognitive function during the first 18 months of therapy and (2) evaluated the influence of co-occurring symptoms, neuropsychological function, and other covariates on relationships. METHODS: We evaluated self-reported cognitive function, using the Patient Assessment of Own Functioning Inventory (PAOFI), and potential covariates (e.g., co-occurring symptom scores and neuropsychological function z-scores) in 158 women receiving aromatase inhibitor (AI) therapy alone, 104 women receiving chemotherapy followed by AI therapy, and 106 non-cancer controls. Patients were assessed before systemic therapy and then every 6 months, for a total of four assessments over 18 months. Controls were assessed at matched time points. Mixed-effects modeling was used to determine longitudinal relationships. RESULTS: Controlling for covariates, patients enrolled before chemotherapy reported poorer global cognitive function (p < 0.001), memory (p < 0.001), language and communication (p < 0.001), and sensorimotor function (p = 0.002) after chemotherapy. These patients reported poorer higher-level cognitive and intellectual functions from before chemotherapy to 12 months after initiation of AI therapy (p < 0.001). Higher levels of depressive symptoms (p < 0.001), anxiety (p < 0.001), and fatigue (p = 0.040) at enrollment were predictors of poorer cognitive function over time. PAOFI total score was a predictor of executive function (p = 0.048) and visual working memory (p = 0.005) z-scores, controlling for covariates. CONCLUSIONS: Findings provide further evidence of poorer self-reported cognitive function after chemotherapy and of relationships between co-occurring symptoms and cognitive changes. AI therapy alone does not have an impact on self-reported cognitive function. Copyright © 2015 John Wiley & Sons, Ltd.


Assuntos
Neoplasias da Mama/psicologia , Cognição , Pós-Menopausa/psicologia , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/terapia , Quimioterapia Adjuvante/efeitos adversos , Transtornos Cognitivos/etiologia , Estudos de Coortes , Terapia Combinada , Fadiga/etiologia , Feminino , Humanos , Memória , Pessoa de Meia-Idade , Autorrelato
12.
Support Care Cancer ; 25(8): 2475-2484, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28247126

RESUMO

PURPOSE: We explored relationships between genetic variability and behaviorally related variables (body mass index and exercise frequency) for inflammation, and perceived cognitive function (PCF) for breast cancer survivors (BCS). Our primary aim was to explore relationships between select single-nucleotide polymorphisms (SNPs) for IL1R1, IL6, TNF genes, and PCF. Our secondary aim was to explore whether body mass index (BMI) and exercise frequency moderate these relationships. METHODS: We conducted an exploratory candidate gene substudy. Saliva samples from participants (N = 101) in a larger, cross-sectional study were genotyped. Multiple linear regression analysis was used to explore relationships between SNPs and PCF, controlling for age, education level, fatigue, and distress. Hierarchical expansion of regression models included main effects for BMI and exercise frequency and interaction effects between BMI, exercise frequency, and each SNP. RESULTS: The most parsimonious regression model included fatigue, exercise frequency, and IL1R1rs2287047 minor alleles (AA+GG) (R 2 = 0.244, adjusted R 2 = 0.220, p = 0.013). No other SNPs were significant. Higher exercise frequency (b = 7.300, p = 0.013) and IL1R1rs2287047 (AA+AG) (b = 6.512, p = 0.025) predicted better PCF. Greater fatigue predicted poorer PCF (b = -2.359, p < 0.01). No interaction was demonstrated between BMI and exercise related to PCF or between BMI, exercise, and SNPs. CONCLUSIONS: Our results suggest a protective relationship between IL1R1rs2287047 (AA+AG) and PCF and provide further evidence supporting exercise as a potential intervention for poorer PCF. Ours is the first study to investigate genetic variability associated with inflammation, behaviorally related variables, and PCF for BCS.


Assuntos
Neoplasias da Mama/genética , Neoplasias da Mama/psicologia , Cognição/fisiologia , Inflamação/genética , Sobreviventes/psicologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/patologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
13.
PLoS Genet ; 10(4): e1004192, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24699359

RESUMO

Annotating and interpreting the results of genome-wide association studies (GWAS) remains challenging. Assigning function to genetic variants as expression quantitative trait loci is an expanding and useful approach, but focuses exclusively on mRNA rather than protein levels. Many variants remain without annotation. To address this problem, we measured the steady state abundance of 441 human signaling and transcription factor proteins from 68 Yoruba HapMap lymphoblastoid cell lines to identify novel relationships between inter-individual protein levels, genetic variants, and sensitivity to chemotherapeutic agents. Proteins were measured using micro-western and reverse phase protein arrays from three independent cell line thaws to permit mixed effect modeling of protein biological replicates. We observed enrichment of protein quantitative trait loci (pQTLs) for cellular sensitivity to two commonly used chemotherapeutics: cisplatin and paclitaxel. We functionally validated the target protein of a genome-wide significant trans-pQTL for its relevance in paclitaxel-induced apoptosis. GWAS overlap results of drug-induced apoptosis and cytotoxicity for paclitaxel and cisplatin revealed unique SNPs associated with the pharmacologic traits (at p<0.001). Interestingly, GWAS SNPs from various regions of the genome implicated the same target protein (p<0.0001) that correlated with drug induced cytotoxicity or apoptosis (p ≤ 0.05). Two genes were functionally validated for association with drug response using siRNA: SMC1A with cisplatin response and ZNF569 with paclitaxel response. This work allows pharmacogenomic discovery to progress from the transcriptome to the proteome and offers potential for identification of new therapeutic targets. This approach, linking targeted proteomic data to variation in pharmacologic response, can be generalized to other studies evaluating genotype-phenotype relationships and provide insight into chemotherapeutic mechanisms.


Assuntos
Antineoplásicos/farmacologia , Polimorfismo de Nucleotídeo Único/genética , Proteínas/genética , Locos de Características Quantitativas/efeitos dos fármacos , Locos de Características Quantitativas/genética , Apoptose/efeitos dos fármacos , Apoptose/genética , Linhagem Celular Tumoral , Cisplatino/farmacologia , Genoma Humano/genética , Estudo de Associação Genômica Ampla/métodos , Genótipo , Projeto HapMap , Humanos , Paclitaxel/farmacologia , Farmacogenética/métodos , Fenótipo , Proteoma/genética , Proteômica/métodos , Fatores de Transcrição , Transcriptoma/genética
15.
Noise Health ; 18(85): 347-354, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27991466

RESUMO

INTRODUCTION: The purpose of this study was to evaluate noise levels in dental offices and to estimate the risk and prevalence of tinnitus and noise-induced hearing loss (NIHL) in practicing dentists. MATERIALS AND METHODS: First, measures were collected of sound pressure levels produced by dental handpieces and dental suction in the University of Oklahoma Health Sciences Center (OUHSC) College of Dentistry. Second, a survey was distributed to members of the Oklahoma Dental Association (ODA). RESULTS: Measurements made in the dental operatory revealed dangerous levels when high-volume suction was in use alone and in conjunction with a dental handpiece. Questionnaire results suggested that practicing dentists report sensorineural hearing loss at a rate broadly in line with national averages. However, dentists reported a higher prevalence of tinnitus symptoms than would be expected based on sample demographics. CONCLUSION: Results from sound level measurements and questionnaire responses indicate that dentists are a population that could be placing their hearing health at risk in a typical daily work environment.


Assuntos
Odontólogos , Perda Auditiva Provocada por Ruído/epidemiologia , Ruído Ocupacional/efeitos adversos , Doenças Profissionais/epidemiologia , Exposição Ocupacional/efeitos adversos , Zumbido/epidemiologia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Oklahoma , Prevalência , Autorrelato
16.
Support Care Cancer ; 23(11): 3219-28, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25832894

RESUMO

PURPOSE: This cross-sectional study was designed to explore potential factors associated with perceived cognitive impairment (PCI) in breast cancer survivors compared to controls and gain insight into perceived levels of severity for cognitive complaints. METHODS: Women (N = 363, 317: breast cancer, 46: healthy controls) completed demographic questionnaire, MD Anderson Symptom Inventory, Attentional Function Index, and Functional Assessment for Cancer Therapy-Cognition. Group classification included pre-chemotherapy, current chemotherapy, and postchemotherapy (<1, >1- < 2, >2- < 5, >5 years). RESULTS: A significant group effect was seen for PCI (F 6, 355 = 7.01, p < 0.0001). Controls reported less PCI than all other groups. Neuropathy was inversely correlated with PCI (r = -0.23; p < 0.0001) for participants with breast cancer. A significant association was demonstrated between exercise frequency and PCI in women exposed to chemotherapy (F 3, 135 = 3.78, p < 0.05). A multiple linear regression model built using forward selection methods explained 24 % of the variance (adjusted R (2)) for PCI in breast cancer participants and included group, body mass index (BMI), exercise, fatigue, and distress. Exercise frequency moderated the relationship between BMI and PCI for breast cancer participants (F 3, 198 = 2.4, p = 0.07) and reduced the negative effects of high BMI. The moderating effect of exercise was significant (F 3, 133 = 3.1, p = 0.03) when limited to participants exposed to chemotherapy. CONCLUSIONS: PCI decreased for women >5 years postchemotherapy. Overweight survivors who exercised frequently reported less PCI than sedentary survivors. Study results provide support for a relationship between BMI and PCI in breast cancer survivors and exercise as a potential intervention for cognitive complaints. Further investigation of the influence of weight and exercise on cognitive function is warranted.


Assuntos
Neoplasias da Mama/psicologia , Transtornos Cognitivos/psicologia , Cognição/fisiologia , Exercício Físico/fisiologia , Qualidade de Vida/psicologia , Adulto , Idoso , Índice de Massa Corporal , Neoplasias da Mama/terapia , Transtornos Cognitivos/diagnóstico , Estudos Transversais , Fadiga/complicações , Fadiga/psicologia , Feminino , Humanos , Pessoa de Meia-Idade , Percepção , Autoimagem , Inquéritos e Questionários , Sobreviventes/psicologia
17.
Clin Adv Hematol Oncol ; 13(7): 441-50, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26353040

RESUMO

Cognitive dysfunction is an increasingly recognized complication of cancer and its treatment. Most research in this arena has found that a subset of patients appear to be vulnerable to this complication even after treatment has ended, and often have difficulties with multitasking, short-term memory, word-finding, attention, or concentration. The mechanisms underlying these cognitive changes are not fully elucidated but may include direct neurotoxic effects of therapy, oxidative damage, and genetic predisposition. Compelling evidence has accumulated for the role of immune dysregulation and neurotoxicity from inflammatory cytokines. A gold standard for subjective or objective assessment of cancer treatment-related cognitive changes has yet to be established. Current options to assess cognitive function include neuropsychological testing, functional neuroimaging, and subjective assessments. Pharmacologic treatment options for this clinical problem are modest and limited. Nonpharmacologic treatments, including cognitive rehabilitation programs, are an emerging area of research for the management of cancer treatment-related cognitive changes.


Assuntos
Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/etiologia , Cognição , Neoplasias/psicologia , Transtornos Cognitivos/terapia , Humanos , Neoplasias/complicações , Neoplasias/terapia , Testes Neuropsicológicos
18.
Pharmacogenet Genomics ; 24(2): 129-32, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24300566

RESUMO

XK469 (NSC 697887) is a selective topoisomerase II ß inhibitor eliminated mainly by aldehyde oxidase I (AOX1). We performed a candidate gene study to investigate whether AOX1 genetic variation contributes to interindividual variability in XK469 clearance. Forty-one AOX1 single nucleotide polymorphisms (SNPs) and seven liver expression quantitative trait loci were genotyped in White patients with advanced refractory solid tumors (n=59) and leukemia (n=33). We found a significant decrease in clearance (τ=-0.32, P=0.003) in solid tumor patients with rs10931910, although it failed to replicate in the leukemia cohort (τ=0.18, P=0.20). Four other AOX1 SNPs were associated with clearance (P=0.01-0.02) in only one of the two cohorts. Our study provides a starting point for future investigations on the functionality of AOX1 SNPs. However, variability in XK469 clearance cannot be attributed to polymorphisms in AOX1.


Assuntos
Aldeído Oxidase/genética , Antineoplásicos/farmacocinética , Fígado/metabolismo , Neoplasias/genética , Quinoxalinas/farmacocinética , Antineoplásicos/administração & dosagem , Ensaios Clínicos Fase I como Assunto , Estudos de Coortes , Variação Genética , Genótipo , Humanos , Neoplasias/tratamento farmacológico , Farmacogenética , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas , Quinoxalinas/administração & dosagem
19.
Int J Palliat Nurs ; 20(7): 334-42, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25062379

RESUMO

STUDY PURPOSE: The aim of this study was to further explore the lived experiences of women with metastatic breast cancer (MBC), to inform the development of interventions to enhance survivorship care for women with advanced disease. METHODOLOGY: Four semi-structured focus groups were conducted with women with MBC. The data was analysed using qualitative content analysis. RESULTS: Participants described the challenges of living with uncertainty, as a result of a lack of information regarding treatment options and symptom management, and a sense of the unknown related to prognosis and survival. Of major concern were changes in role functioning, altered relationships, and self-image. CONCLUSION: Women with metastatic breast cancer must cope with dramatic changes in all aspects of their lives. Clinicians should tailor survivorship care and evidence-based interventions to individuals' concerns with changes in role functioning, fatigue, relationships, and self-image. A multidisciplinary approach should be used to address practical and existential concerns focused on improving quality of life.


Assuntos
Neoplasias da Mama/patologia , Neoplasias da Mama/psicologia , Qualidade de Vida , Adulto , Idoso , Imagem Corporal , Feminino , Grupos Focais , Humanos , Relações Interpessoais , Pessoa de Meia-Idade , Metástase Neoplásica , Prognóstico , Pesquisa Qualitativa , Incerteza
20.
Cancer Nurs ; 47(1): 43-55, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-35984916

RESUMO

BACKGROUND: Androgen deprivation therapy (ADT) for prostate cancer is associated with cardiovascular comorbidities and numerous adverse effects decreasing health-related quality of life. Both exercise and dietary interventions have shown promise in reducing ADT-related negative sequelae. However, feasibility for personalized combined exercise/nutrition/education interventions is not well established. OBJECTIVE: The purpose of this randomized, controlled, mixed-methods pilot study was to evaluate the feasibility of a nurse-led, telephone-delivered education, exercise, and nutrition intervention, Staying Strong & Healthy, to minimize ADT-related cardiovascular/metabolic risks and symptoms. METHODS: Staying Strong & Healthy involves individually tailored education, exercise (aerobic and resistance), and nutrition intervention delivered over 6 months and was compared with attention control. The primary quantitative outcome measure was change from baseline in low-density lipoprotein. Secondary outcomes included change in lipid levels (total cholesterol, high-density lipoprotein, low-density lipoprotein, and triglycerides), fasting blood glucose, hemoglobin A 1c , health-related quality of life, and diet quality. Assessments were performed at baseline, 6 months, and 12 months. RESULTS: Feasibility was demonstrated by low attrition rates and high participant satisfaction. No between-group differences were demonstrated in the cardiovascular/metabolic outcomes. Significant within-group improvements were noted for high-density lipoprotein and hemoglobin A 1c in the intervention group. CONCLUSION: The study results indicate that participation in a personalized, nurse-delivered exercise, nutrition, and educational intervention is feasible and acceptable to men with prostate cancer receiving ADT. IMPLICATIONS FOR PRACTICE: Future randomized controlled research powered to detect significant differences is needed to confirm the impact of the Staying Strong & Healthy intervention on reduction of the cardiovascular/metabolic impact of ADT for men with prostate cancer.


Assuntos
Neoplasias da Próstata , Qualidade de Vida , Masculino , Humanos , Antagonistas de Androgênios/efeitos adversos , Androgênios , Projetos Piloto , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/complicações , Terapia por Exercício/métodos , Lipoproteínas HDL , Lipoproteínas LDL
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA