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1.
Cancer ; 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31553487

RESUMO

BACKGROUND: Dasatinib, a potent Bcr-Abl tyrosine kinase inhibitor, is approved for the treatment of chronic-phase chronic myeloid leukemia (CML-CP) in the frontline and salvage settings. Notable side effects include pleural effusions and myelosuppression. Dasatinib at 50 mg daily has previously been reported to be active and better tolerated than the approved 100-mg daily dose. The aim of this study was to update the long-term follow-up results of dasatinib at 50 mg daily as frontline therapy for CML-CP. METHODS: Eighty-three patients with newly diagnosed CML-CP received dasatinib at 50 mg daily. Eligibility and response criteria were standards used in previous protocols. RESULTS: After a minimum follow-up of 12 months, 81 patients were evaluable. Two patients came off the study in less than 3 months. The rates of BCR-ABL1 transcript levels (International Standard) at ≤10% and ≤1% at 3 months were 96% and 77%, respectively. The cumulative rates for a complete cytogenetic response by 6 and 12 months were 77% and 95%, respectively. The cumulative rates for a major molecular response, a molecular response with a 4.0-log reduction, and a molecular response with a 4.5-log reduction by 12 months were 81%, 55%, and 49%, respectively. Twenty-one patients (25%) had treatment interruptions for a median of 13 days (range, 4-64 days). Five patients (6%) developed pleural effusions; 4 of these patients (80%) required a dose reduction. Two patients (2%) failed to achieve any cytogenetic or molecular response and were taken off the study. At a median follow-up of 24 months, none of the patients had disease transformation to an accelerated or blastic phase. The 2-year event-free and overall survival rates were 100%. CONCLUSIONS: These updated results continue to support 50 mg of dasatinib daily as an effective and safe dose for early CML-CP.

2.
Cancer Immunol Res ; 7(9): 1412-1425, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31337659

RESUMO

Adoptive T-cell therapy using high-affinity T-cell receptors (TCR) to target tumor antigens has potential for improving outcomes in high-grade serous ovarian cancer (HGSOC) patients. Ovarian tumors develop a hostile, multicomponent tumor microenvironment containing suppressive cells, inhibitory ligands, and soluble factors that facilitate evasion of antitumor immune responses. Developing and validating an immunocompetent mouse model of metastatic ovarian cancer that shares antigenic and immunosuppressive qualities of human disease would facilitate establishing effective T-cell therapies. We used deep transcriptome profiling and IHC analysis of human HGSOC tumors and disseminated mouse ID8VEGF tumors to compare immunologic features. We then evaluated the ability of CD8 T cells engineered to express a high-affinity TCR specific for mesothelin, an ovarian cancer antigen, to infiltrate advanced ID8VEGF murine ovarian tumors and control tumor growth. Human CD8 T cells engineered to target mesothelin were also evaluated for ability to kill HLA-A2+ HGSOC lines. IHC and gene-expression profiling revealed striking similarities between tumors of both species, including processing/presentation of a leading candidate target antigen, suppressive immune cell infiltration, and expression of molecules that inhibit T-cell function. Engineered T cells targeting mesothelin infiltrated mouse tumors but became progressively dysfunctional and failed to persist. Treatment with repeated doses of T cells maintained functional activity, significantly prolonging survival of mice harboring late-stage disease at treatment onset. Human CD8 T cells engineered to target mesothelin were tumoricidal for three HGSOC lines. Treatment with engineered T cells may have clinical applicability in patients with advanced-stage HGSOC.

3.
PLoS One ; 14(6): e0217868, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31166958

RESUMO

BACKGROUND: Pancreatic tumor cells may avoid immune surveillance by releasing the transmembrane major histocompatibility complex class I chain-related A (MICA) protein in soluble form (s-MICA). We hypothesized that the presence of the A5.1 polymorphism in the MICA gene, which encodes a truncated MICA protein, is associated with higher s-MICA levels and increased pancreatic cancer risk. METHODS: MICA alleles and s-MICA levels were measured in 121 pancreatic cancer cases and 419 controls. General linear regression with a log transformation assessed geometric means of s-MICA levels across MICA alleles. Unconditional logistic regression was used to calculate the odds ratio (OR) and 95% confidence intervals (CI) for pancreatic cancer associated with MICA alleles. RESULTS: After multivariate adjustment, participants with at least one copy of the A5.1 allele versus no A5.1 allele had 1.35 (95% CI: 1.05-1.74) times greater s-MICA levels (1.65 times higher for cases and 1.28, for controls) and increased risk of pancreatic cancer (OR = 1.91, 95% CI: 1.05-3.48). CONCLUSIONS: Our study suggests higher risk of pancreatic cancer among those with the MICA A5.1 polymorphism, which may be explained by an increase in s-MICA secretion and impaired immune response. IMPACT: These findings provide further evidence at the genetic and molecular level of the important role of MICA in pancreatic cancer development, and may have important implications with regards to pancreatic cancer screening.

4.
Nat Genet ; 2018 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-30510241

RESUMO

To further dissect the genetic architecture of colorectal cancer (CRC), we performed whole-genome sequencing of 1,439 cases and 720 controls, imputed discovered sequence variants and Haplotype Reference Consortium panel variants into genome-wide association study data, and tested for association in 34,869 cases and 29,051 controls. Findings were followed up in an additional 23,262 cases and 38,296 controls. We discovered a strongly protective 0.3% frequency variant signal at CHD1. In a combined meta-analysis of 125,478 individuals, we identified 40 new independent signals at P < 5 × 10-8, bringing the number of known independent signals for CRC to ~100. New signals implicate lower-frequency variants, Krüppel-like factors, Hedgehog signaling, Hippo-YAP signaling, long noncoding RNAs and somatic drivers, and support a role for immune function. Heritability analyses suggest that CRC risk is highly polygenic, and larger, more comprehensive studies enabling rare variant analysis will improve understanding of biology underlying this risk and influence personalized screening strategies and drug development.

5.
PLoS One ; 13(7): e0199643, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29969495

RESUMO

Neuronal nicotinic acetylcholine receptors (nAChRs) of the cholinergic system have been linked to antinociception, and therefore could be an alternative target for pain alleviation. nAChR activity has been shown to be regulated by the nicotinic modulator, lynx1, which forms stable complexes with nAChRs and has a negative allosteric action on their function. The objective in this study was to investigate the contribution of lynx1 to nicotine-mediated antinociception. Lynx1 contribution was investigated by mRNA expression analysis and electrophysiological responses to nicotine in the dorsal raphe nucleus (DRN), a part of the pain signaling pathway. In vivo antinociception was investigated in a test of nociception, the hot-plate analgesia assay with behavioral pharmacology. Lynx1/α4ß2 nAChR interactions were investigated using molecular dynamics computational modeling. Nicotine evoked responses in serotonergic and GABAergic neurons in the DRN are augmented in slices lacking lynx1 (lynx1KO). The antinociceptive effect of nicotine and epibatidine is enhanced in lynx1KO mice and blocked by mecamylamine and DHßE. Computer simulations predict preferential binding affinity of lynx1 to the α:α interface that exists in the stoichiometry of the low sensitivity (α4)3(ß2)2 nAChRs. Taken together, these data point to a role of lynx1 in mediating pain signaling in the DRN through preferential affinity to the low sensitivity α4ß2 nAChRs. This study suggests that lynx1 is a possible alternative avenue for nociceptive modulation outside of opioid-based strategies.

6.
Am J Orthopsychiatry ; 2018 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-30010364

RESUMO

Premature termination is a pervasive barrier to effective implementation of outpatient psychotherapy that frequently results in poorer outcomes for clients as well as poor resource allocation for clients, therapists, and society. Despite its high prevalence and cost, premature termination remains poorly understood, especially from the clients' perspective. The current study addressed some gaps in the literature using a national online survey design that permitted investigation of a broad range of potential predictors of premature termination. Participants were 278 respondents from Amazon.com's Mechanical Turk who completed an online survey about their treatment history, their most recent outpatient therapy experience and therapist, termination status, reasons for terminating prematurely (if applicable), treatment satisfaction, and demographics. Results indicated that being a woman, identifying as a sexual minority, and having a therapist low in perceived multicultural competence were associated with increased risk of premature termination. However, the best predictors of premature termination were a weak therapeutic alliance and symptoms of depression. These results support previous research that shows both client and therapist variables contribute to premature termination. Potential interventions that can be implemented by providers or agencies to reduce premature termination are discussed, along with limitations of the study and recommendations for future research. (PsycINFO Database Record

7.
Eur J Clin Nutr ; 72(8): 1128-1135, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29904184

RESUMO

BACKGROUND/OBJECTIVES: Folate, vitamin B6, vitamin B12, and methionine are involved in DNA synthesis and methylation and thus may modulate pancreatic cancer risk. We investigated these associations in a population-based case-control study conducted in 1994-1998. SUBJECTS/METHODS: Cases (n = 150) were identified from all hospitals in the metropolitan areas of the Twin Cities and the Mayo Clinic, Minnesota. Controls (n = 459) were selected randomly from the general population and were frequency matched to cases by age, sex, and race. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI) for risk of pancreatic cancer in relation to intake of nutrients considered. RESULTS: Dietary intake of folate was associated with a reduced pancreatic cancer risk [OR (95% CI) for quartile (Q) 4 vs. Q1: 0.31 (0.12-0.78)]. A composite score (range from 2 to 8), reflecting combined dietary intake of folate and vitamin B6, was also inversely associated with pancreatic cancer risk [OR (95% CI) for Q4 vs. Q1: 0.24 (0.08-0.70)]. Null associations were found for intake of vitamin B12 and methionine. CONCLUSIONS: Dietary folate intake was associated with a reduced pancreatic cancer risk, and this association became stronger when dietary intake of folate and vitamin B6 was combined in analysis.

8.
Carcinogenesis ; 2018 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-29800239

RESUMO

Diets with high inflammatory potential are suspected to increase risk for pancreatic cancer (PC). Using pooled analyses, we examined whether this association applies to populations from different geographic regions and population subgroups with varying risks for PC, including variation in ABO blood type. Data from six case-control studies (cases, n=2,414; controls, n=4,528) in the Pancreatic Cancer Case-Control Consortium (PanC4) were analyzed, followed by replication in five nested case-control studies (cases, n=1,268; controls, n=4,215) from the Pancreatic Cancer Cohort Consortium (PanScan). Two polymorphisms in the ABO locus (rs505922 and rs8176746) were used to infer participants' blood types. Dietary questionnaire-derived nutrient/food intake was used to compute energy-adjusted dietary inflammatory index (DII®) scores to assess inflammatory potential of diet. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using multivariable-adjusted logistic regression. Higher E-DII scores, reflecting greater inflammatory potential of diet, were associated with increased PC risk in PanC4 (ORQ5 vs. Q1=2.20, 95% CI=1.85-2.61, Ptrend<0.0001; ORcontinuous=1.20, 95% CI=1.17-1.24), and PanScan (ORQ5 vs. Q1=1.23, 95% CI=0.92-1.66, Ptrend=0.008; ORcontinuous=1.09, 95% CI=1.02-1.15). As expected, genotype-derived non-O blood type was associated with increased PC risk in both the PanC4 and PanScan studies. Stratified analyses of associations between E-DII quintiles and PC by genotype-derived ABO blood type did not show interaction by blood type (Pinteraction=0.10 in PanC4 and Pinteraction=0.13 in PanScan). The results show that consuming a pro-inflammatory diet and carrying non-O blood type are each individually, but not interactively, associated with increased PC risk.

9.
Am J Emerg Med ; 36(9): 1603-1607, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29371045

RESUMO

BACKGROUND: Pain management guidelines in the emergency department (ED) may reduce time to analgesia administration (TTA). Intranasal fentanyl (INF) is a safe and effective alternative to intravenous opiates. The effect of an ED pain management guideline providing standing orders for nurse-initiated administration of intranasal fentanyl (INF) is not known. The objective of this study was to determine the impact of a pediatric ED triage-based pain protocol utilizing intranasal fentanyl (INF) on time to analgesia administration (TTA) and patient and parent satisfaction. METHODS: This was a prospective study of patients 3-17 years with an isolated orthopedic injury presenting to a pediatric ED before and after instituting a triage-based pain guideline allowing for administration of INF by triage nurses. Our primary outcome was median TTA and secondary outcomes included the proportion of patients who received INF for pain, had unnecessary IV placement, and patient and parent satisfaction. RESULTS: We enrolled 132 patients; 72 pre-guideline, 60 post-guideline. Demographics were similar between groups. Median TTA was not different between groups (34.5 min vs. 33 min, p = .7). Utilization of INF increased from 41% pre-guideline to 60% post-guideline (p = .01) and unnecessary IV placement decreased from 24% to 0% (p = .002). Patients and parents preferred the IN route for analgesia administration. CONCLUSION: A triage-based pain protocol utilizing INF did not reduce TTA, but did result in increased INF use, decreased unnecessary IV placement, and was preferred by patients and parents to IV medication. INF is a viable analgesia alternative for children with isolated extremity injuries.

10.
Int J Cancer ; 142(2): 251-261, 2018 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-28921575

RESUMO

Nitrate and nitrite are precursors of N-nitroso compounds (NOC), probable human carcinogens that cause pancreatic tumors in animals. Disinfection by-products (DBP) exposures have also been linked with digestive system cancers, but few studies have evaluated relationships with pancreatic cancer. We investigated the association of pancreatic cancer with these drinking water contaminants and dietary nitrate/nitrite in a cohort of postmenopausal women in Iowa (1986-2011). We used historical monitoring and treatment data to estimate levels of long-term average nitrate and total trihalomethanes (TTHM; the sum of the most prevalent DBP class) and the duration exceeding one-half the maximum contaminant level (>½ MCL; 5 mg/L nitrate-nitrogen, 40 µg/L TTHM) among participants on public water supplies (PWS) >10 years. We estimated dietary nitrate and nitrite intakes using a food frequency questionnaire. We computed hazard ratios (HR) and 95% confidence intervals (CI) using Cox regression and evaluated nitrate interactions with smoking and vitamin C intake. We identified 313 cases among 34,242 women, including 152 with >10 years PWS use (N = 15,710). Multivariable models of average nitrate showed no association with pancreatic cancer (HRp95vs. Q1 = 1.16, 95% CI: 0.51-2.64). Associations with average TTHM levels were also null (HRQ4vs. Q1 = 0.70, 95% CI:0.42-1.18). We observed no trend with increasing years of exposure to either contaminant at levels >½ MCL. Positive associations were suggested in the highest dietary nitrite intake from processed meat (HRp95vs. Q1 = 1.66, 95% CI 1.00-2.75;ptrend = 0.05). We found no interactions of nitrate with known modifiers of endogenous NOC formation. Our results suggest that nitrite intake from processed meat may be a risk factor for pancreatic cancer.


Assuntos
Desinfecção/métodos , Nitratos/efeitos adversos , Nitritos/efeitos adversos , Neoplasias Pancreáticas/etiologia , Idoso , Feminino , Seguimentos , Humanos , Iowa , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Pós-Menopausa , Prognóstico , Estudos Prospectivos , Fatores de Risco
11.
Child Adolesc Psychiatr Clin N Am ; 27(1): 63-76, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29157503

RESUMO

Prevention and management of childhood obesity remains a public health priority and necessitates an integrated chronic care approach. Obesity prevention efforts should focus on healthy family-based lifestyle modifications. The United States Prevention Services Task Force recommends children older than age 6 of years be screened for obesity and, if clinically indicated, be referred for moderate to high intensity comprehensive behavioral interventions. Childhood obesity and its comorbidities affect most medical specialties. A shared understanding of prevention strategies, lifestyle recommendations, screening guidelines for comorbidities, and stages of treatment will allow for more integrated and collaborative care.


Assuntos
Terapia Comportamental , Política Nutricional , Obesidade Pediátrica/prevenção & controle , Obesidade Pediátrica/terapia , Criança , Exercício , Humanos , Obesidade Pediátrica/diagnóstico , Obesidade Pediátrica/epidemiologia , Estados Unidos
12.
Biochim Biophys Acta Bioenerg ; 1858(12): 991-998, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28947253

RESUMO

NAD+ is a dinucleotide cofactor with the potential to accept electrons in a variety of cellular reduction-oxidation (redox) reactions. In its reduced form, NADH is a ubiquitous cellular electron donor. NAD+, NADH, and the NAD+/NADH ratio have long been known to control the activity of several oxidoreductase enzymes. More recently, enzymes outside those participating directly in redox control have been identified that sense these dinucleotides, including the sirtuin family of NAD+-dependent protein deacylases. In this review, we highlight examples of non-redox enzymes that are controlled by NAD+, NADH, or NAD+/NADH. In particular, we focus on the sirtuin family and assess the current evidence that the sirtuin enzymes sense these dinucleotides and discuss the biological conditions under which this might occur; we conclude that sirtuins sense NAD+, but neither NADH nor the ratio. Finally, we identify future studies that might be informative to further interrogate physiological and pathophysiological changes in NAD+ and NADH, as well as enzymes like sirtuins that sense and respond to redox changes in the cell.


Assuntos
NAD/química , Oxirredução , Sirtuínas/química , Fenômenos Bioquímicos , Transporte de Elétrons , NAD/metabolismo , Oxirredutases/química , Oxirredutases/metabolismo , Sirtuínas/metabolismo
13.
Nat Commun ; 8: 15878, 2017 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-28722015

RESUMO

TRPV1 is an ion channel activated by heat and pungent agents including capsaicin, and has been extensively studied in nociception of sensory neurons. However, the location and function of TRPV1 in the hippocampus is debated. We found that TRPV1 is expressed in oriens-lacunosum-moleculare (OLM) interneurons in the hippocampus, and promotes excitatory innervation. TRPV1 knockout mice have reduced glutamatergic innervation of OLM neurons. When activated by capsaicin, TRPV1 recruits more glutamatergic, but not GABAergic, terminals to OLM neurons in vitro. When TRPV1 is blocked, glutamatergic input to OLM neurons is dramatically reduced. Heterologous expression of TRPV1 also increases excitatory innervation. Moreover, TRPV1 knockouts have reduced Schaffer collateral LTP, which is rescued by activating OLM neurons with nicotine-via α2ß2-containing nicotinic receptors-to bypass innervation defects. Our results reveal a synaptogenic function of TRPV1 in a specific interneuron population in the hippocampus, where it is important for gating hippocampal plasticity.

14.
Mol Carcinog ; 56(9): 2158-2164, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28470829

RESUMO

Pancreatic cancer is diagnosed at a late stage and has one of the highest cancer mortality rates in the United States, creating an urgent need for novel early detection tools. A candidate biomarker for use in early detection is the soluble MHC class I-related chain A (s-MICA) ligand, which pancreatic tumors shed to escape immune detection. The objective of this study was to define the association between s-MICA levels and pancreatic cancer, in a population-based case-control study. S-MICA was measured in 143 pancreatic cancer cases and 459 controls. Unconditional logistic regression was used to calculate odds ratio (OR) for pancreatic cancer and 95% confidence intervals (CI). There was a positive association between increasing s-MICA levels and pancreatic cancer: compared to the lowest tertile, the ORs for pancreatic cancer were 1.25 (95%CI: 0.75-2.07) and 2.10 (95%CI: 1.29-3.42) in the second and highest tertiles, respectively (P-trend = 0.02). Our study supports previous work demonstrating a positive association between plasma s-MICA levels and pancreatic cancer.


Assuntos
Biomarcadores Tumorais/sangue , Antígenos de Histocompatibilidade Classe I/sangue , Neoplasias Pancreáticas/sangue , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/diagnóstico
15.
Nutrients ; 9(5)2017 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-28468303

RESUMO

Pancreatic cancer is one of the most fatal common cancers affecting both men and women, representing about 3% of all new cancer cases in the United States. In this study, we aimed to investigate the association of pancreatic cancer risk with alcohol consumption as well as folate intake. We performed a case-control study of 384 patients diagnosed with pancreatic cancer from May 2004 to December 2009 and 983 primary care healthy controls in a largely white population (>96%). Our findings showed no significant association between risk of pancreatic cancer and either overall alcohol consumption or type of alcohol consumed (drinks/day). Our study showed dietary folate intake had a modest effect size, but was significantly inversely associated with pancreatic cancer (odds ratio (OR) = 0.99, p < 0.0001). The current study supports the hypothesis that pancreatic cancer risk is reduced with higher food-based folate intake.


Assuntos
Consumo de Bebidas Alcoólicas/efeitos adversos , Dieta , Ácido Fólico/administração & dosagem , Neoplasias Pancreáticas/epidemiologia , Idoso , Índice de Massa Corporal , Estudos de Casos e Controles , Suplementos Nutricionais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estado Nutricional , Fatores de Risco
16.
Cell Metab ; 25(4): 838-855.e15, 2017 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-28380376

RESUMO

Sirtuins are NAD+-dependent protein deacylases that regulate several aspects of metabolism and aging. In contrast to the other mammalian sirtuins, the primary enzymatic activity of mitochondrial sirtuin 4 (SIRT4) and its overall role in metabolic control have remained enigmatic. Using a combination of phylogenetics, structural biology, and enzymology, we show that SIRT4 removes three acyl moieties from lysine residues: methylglutaryl (MG)-, hydroxymethylglutaryl (HMG)-, and 3-methylglutaconyl (MGc)-lysine. The metabolites leading to these post-translational modifications are intermediates in leucine oxidation, and we show a primary role for SIRT4 in controlling this pathway in mice. Furthermore, we find that dysregulated leucine metabolism in SIRT4KO mice leads to elevated basal and stimulated insulin secretion, which progressively develops into glucose intolerance and insulin resistance. These findings identify a robust enzymatic activity for SIRT4, uncover a mechanism controlling branched-chain amino acid flux, and position SIRT4 as a crucial player maintaining insulin secretion and glucose homeostasis during aging.


Assuntos
Amidoidrolases/metabolismo , Insulina/metabolismo , Leucina/metabolismo , Lisina/metabolismo , Proteínas Mitocondriais/metabolismo , Sirtuínas/metabolismo , Sequência de Aminoácidos , Animais , Carbono-Carbono Ligases/metabolismo , Glucose/metabolismo , Células HEK293 , Homeostase , Humanos , Resistência à Insulina , Análise do Fluxo Metabólico , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas Mitocondriais/química , Modelos Moleculares , Filogenia , Sirtuínas/química
17.
Cancer Cell ; 31(3): 311-325, 2017 03 13.
Artigo em Inglês | MEDLINE | ID: mdl-28292435

RESUMO

T cell dysfunction in solid tumors results from multiple mechanisms. Altered signaling pathways in tumor cells help produce a suppressive tumor microenvironment enriched for inhibitory cells, posing a major obstacle for cancer immunity. Metabolic constraints to cell function and survival shape tumor progression and immune cell function. In the face of persistent antigen, chronic T cell receptor signaling drives T lymphocytes to a functionally exhausted state. Here we discuss how the tumor and its microenvironment influences T cell trafficking and function with a focus on melanoma, and pancreatic and ovarian cancer, and discuss how scientific advances may help overcome these hurdles.


Assuntos
Neoplasias/imunologia , Linfócitos T/imunologia , Microambiente Tumoral , Aminoácidos/metabolismo , Citotoxicidade Imunológica , Ácidos Graxos/metabolismo , Genes p53 , Glucose/metabolismo , Humanos , Ácido Láctico/metabolismo , Neoplasias/metabolismo , Neoplasias/terapia , Receptores de Antígenos de Linfócitos T/fisiologia
18.
Qual Life Res ; 26(7): 1761-1766, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28243994

RESUMO

PURPOSE: Little is known about specific concerns facing long-term melanoma survivors. The goal of this study was to compare quality of life (QOL) and mental health between long-term melanoma survivors and population controls. METHODS: Participants from a previously conducted case-control study of risk factors for melanoma were recruited for a cross-sectional survey. Generic QOL and emotional health were measured using the SF-36 and Hospital Anxiety and Depression Scale questionnaires. A total of 724 melanoma survivors and 660 controls participated. Most melanoma survivors had stage I disease (85.6%); mean time from diagnosis was 9.6 ± 1.0 years. Comparisons of QOL measures between melanoma survivors and controls were conducted using regression models, adjusting for potential confounders. RESULTS: Melanoma survivors, compared to controls, reported statistically significant but only slightly higher physical functioning and bodily pain QOL subscale scores than controls and otherwise similar QOL as measured by the remaining six SF-36 subscale scores. Prevalence of anxiety (18.1% vs. 19.3%, adjusted OR = 1.00 (0.74, 1.36); p = 1.00) and depression (7.2% vs. 9.8%, adjusted OR = 0.74 (0.48, 1.16); p = 1.00) were similar between melanoma survivors and controls. CONCLUSION: Long-term early stage melanoma survivors report similar general QOL and mental health compared to population controls. Further research is needed to identify concerns more specific to melanoma.


Assuntos
Melanoma/psicologia , Qualidade de Vida/psicologia , Sobreviventes/psicologia , Adulto , Estudos de Casos e Controles , Estudos Transversais , Feminino , Humanos , Masculino , Melanoma/mortalidade , Prevalência , Fatores de Risco
19.
Cancer Epidemiol Biomarkers Prev ; 26(4): 607-613, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28254810

RESUMO

Introduction: Melanoma is considered a generally preventable cancer, with excessive ultraviolet radiation (UVR) exposure being a strong causal factor. UVR exposure following a melanoma diagnosis can be modified to reduce risk of second primary melanomas. The goal of this study was to compare measures of UVR exposure and protection behaviors between long-term melanoma survivors and controls.Methods: Participants from a previously conducted case-control study were recruited for a cross-sectional survey. Melanoma cases were 25 to 59 years old at diagnosis; controls were age and sex matched. Participants were asked about UVR exposure and protection measures used in the past year, and comparisons between melanoma survivors and controls were conducted using logistic regression models, adjusting for potential confounders.Results: A total of 724 (62.0%) long-term melanoma survivors and 660 (59.9%) controls completed the follow-up survey. Melanoma survivors were significantly less likely to report high sun exposure on a typical weekday [OR, 0.72 (0.55-0.94)], sunburns [OR, 0.40 (0.30-0.53)], or indoor tanning [OR, 0.20 (0.09-0.44)] than controls; however, high sun exposure on a typical weekend day was similar. Report of optimal sun protection behaviors was higher in melanoma survivors compared with controls. However, a few melanoma survivors reported indoor tanning, 10% reported intentionally seeking sun to tan, and 20% reported sunburns.Conclusions: Although long-term melanoma survivors reported healthier UVR exposure and protection behaviors compared with controls, a sizeable proportion still reported elevated sun exposure, sunburns, and suboptimal UVR protection behaviors.Impact: Opportunities remain for improving sun protection to reduce future melanoma risk among melanoma survivors. Cancer Epidemiol Biomarkers Prev; 26(4); 607-13. ©2017 AACR.


Assuntos
Sobreviventes de Câncer/estatística & dados numéricos , Comportamentos Relacionados com a Saúde , Melanoma/prevenção & controle , Segunda Neoplasia Primária/prevenção & controle , Prevenção Secundária/estatística & dados numéricos , Neoplasias Cutâneas/prevenção & controle , Raios Ultravioleta/efeitos adversos , Adulto , Estudos de Casos e Controles , Estudos Transversais , Feminino , Seguimentos , Humanos , Modelos Logísticos , Masculino , Melanoma/epidemiologia , Melanoma/mortalidade , Pessoa de Meia-Idade , Minnesota/epidemiologia , Roupa de Proteção/estatística & dados numéricos , Fatores de Risco , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/mortalidade , Queimadura Solar/epidemiologia , Queimadura Solar/prevenção & controle , Protetores Solares
20.
Cultur Divers Ethnic Minor Psychol ; 23(1): 134-142, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27845525

RESUMO

OBJECTIVE: Multiracial feminist theory proposes that the meaning of feminism and the pathways to feminist identity may differ on the basis of cross-cutting social categories such as ethnicity and gender. However, there is currently little research that has included systematic examination of feminist identity among women and men from diverse ethnic backgrounds. METHOD: We examined feminist orientations among 1,140 undergraduates (70% women) at a Hispanic-Serving Institution who identified as African American, Asian American, European American, or Latina/o. Three related research aims were assessed through a combination of closed- and open-ended questions. First, we examined whether the meaning of the term feminism differed depending on participants' ethnicity or gender. We then tested for ethnic and gender variation in rates of feminist identity. Lastly, we examined participants' reasons for either identifying or not identifying as feminists. RESULTS: Ethnic and gender differences were obtained across each of the 3 research aims. For example, there were significant ethnic differences in rates of feminist identity among women, but not among men. CONCLUSION: Relative to past research, through the current study, we have provided an especially comprehensive examination of how ethnicity and gender interact to shape feminist attitudes. Consistent with multiracial feminist theory, findings demonstrated that attitudes about feminism vary as a function of both gender and ethnicity, yet key ethnic and gender similarities also emerged. (PsycINFO Database Record


Assuntos
Grupos Étnicos/psicologia , Feminilidade , Feminismo , Adulto , Afro-Americanos/psicologia , Americanos Asiáticos/psicologia , Grupos de Populações Continentais/psicologia , Grupo com Ancestrais do Continente Europeu/psicologia , Feminino , Identidade de Gênero , Hispano-Americanos/psicologia , Humanos , Masculino , Fatores Sexuais , Estudantes
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