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Background: (1)Sarcopenia, or low skeletal mass index (SMI), contributes to higher lung cancer mortality. The SMI at third lumbar vertebrae (L3) is the reference standard for body composition analysis. However, there is a need to explore the validity of alternative landmarks in this population. We compared the agreement of sarcopenia identification at the first lumbar (L1) and second lumbar (L2) to L3 in non-Hispanic Black (NHB) and White (NHW) individuals with lung cancer. Methods: (2)This retrospective, cross-sectional study included 214 NHB and NHW adults with lung cancer. CT scans were analyzed to calculate the SMI at L1, L2, and L3. T-tests, chi-square, Pearson's correlation, Cohen's kappa, sensitivity, and specificity analysis were used. Results: (3)Subjects presented with a mean age of 68.4 ± 9.9 years and BMI of 26.3 ± 6.0 kg/m2. Sarcopenia prevalence varied from 19.6% at L1 to 39.7% at L3. Cohen's kappa coefficient was 0.46 for L1 and 0.64 for L2, indicating weak and moderate agreement for the identification of sarcopenia compared to L3. Conclusions: (4)Sarcopenia prevalence varied greatly depending on the vertebral landmark used for assessment. Using L2 or L1 alone resulted in a 16.8% and 23.8% misclassification of sarcopenia in this cohort of individuals with lung cancer.
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This Perspective highlights the work of Dr. Daniela Novick in the field of cytokine biology. Using affinity chromatography to characterize cytokine-binding proteins, she identified soluble forms of the receptors as well as binding proteins for several cytokines, including tumor necrosis factor, interleukin (IL) 6, IL-18 and IL-32. Importantly, her work has been key in the development of monoclonal antibodies against interferons and cytokines. This Perspective discusses her contribution to the field and highlights her recent review on this topic.
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Citocinas , Interleucina-6 , Feminino , Humanos , Citocinas/metabolismo , Interleucina-6/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Interferons , Anticorpos Monoclonais/uso terapêuticoRESUMO
Background: Lung cancer incidence and mortality rates are higher in Non-Hispanic Black (NHB) compared to Non-Hispanic White (NHW) individuals in the Chicago metropolitan area, which may be related to exposure to chronic stress which may increase inflammation. Specific aim: We investigated disparities in inflammation as measured by neutrophil to lymphocyte ratio (NLR) in individuals with lung cancer by race and by neighborhood concentrated disadvantage index (CDI). Methods: This retrospective, cross-sectional study included 263 NHB and NHW adults with lung cancer. We analyzed NLR as a continuous and categorical variable to determine degree and prevalence of inflammation. We used Mann Whitney U, t-tests, Chi square tests, linear and logistic regression models as appropriate. Results: More than 60% of subjects had inflammation (NLR ≥ 3) at lung cancer diagnosis. The degree of inflammation was significantly lower in NHB (NLR 5.50 +/- 7.45) compared to NHW individuals (NLR 6.53 +/- 6.53; p=0.01) but did not differ by neighborhood CDI. The prevalence of inflammation (NLR ≥ 3) was significantly lower in NHB (55.07%) compared to NHW individuals (71.20%; p<0.01) and in those from the most disadvantaged (54.07%) compared to the least disadvantaged (71.88%; p<0.01) neighborhoods. Conclusion: At lung cancer diagnosis, there is a lower degree and prevalence of inflammation in NHB compared to NHW individuals, and lower prevalence in those residing in the most disadvantaged neighborhoods. Further research is needed to determine mechanisms of inflammation that may be contributing to lung cancer disparities as well as whether NLR is an appropriate biomarker when examining racial differences in inflammation.
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Neoplasias Pulmonares , Brancos , Adulto , Humanos , Chicago/epidemiologia , Estudos Transversais , Estudos Retrospectivos , Negro ou Afro-Americano , Inflamação , Neoplasias Pulmonares/epidemiologiaRESUMO
Rationale and objectives: To validate skeletal muscle and adipose tissues cross sectional area (CSA) and densities between a fully automated neural network (test program) and a semi-automated program requiring human correction (reference program) for lumbar 1 (L1) and lumbar 2 (L2) CT scans in patients with lung cancer. Materials and methods: Agreement between the reference and test programs was measured using Dice-similarity coefficient (DSC) and Bland-Altman plots with limits of agreement within 1.96 standard deviation. Results: A total of 49 L1 and 47 L2 images were analyzed from patients with lung cancer (mean age = 70.51 ± 9.48 years; mean BMI = 27.45 ± 6.06 kg/m2; 71% female, 55% self-identified as Black and 96% as non-Hispanic ethnicity). The DSC indicates excellent overlap (>0.944) or agreement between the two measurement methods for muscle, visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) CSA and all tissue densities at L1 and L2. The DSC was lowest for intermuscular adipose tissue (IMAT) CSA at L1 (0.889) and L2 (0.919). Conclusion: The use of a fully automated neural network to analyze body composition at L1 and L2 in patients with lung cancer is valid for measuring skeletal muscle and adipose tissue CSA and densities when compared to a reference program. Further validation in a more diverse sample and in different disease and health states is warranted to increase the generalizability of the test program at L1 and L2.
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(1) Background: There are currently very few interventions performed within a community setting that compare the effects of physical activity (PA) versus PA plus weight loss on cancer and chronic disease risk in older African Americans. Therefore, we investigated the impact of an 8 week (24 session) PA intervention compared to a PA plus weight loss intervention on fat mass, glucose metabolism, and markers of inflammation in older, overweight and obese African Americans. (2) Methods: Subjects were randomized to a PA (n = 83) or PA plus weight loss (n = 72) intervention that met three times weekly for 8 weeks. At baseline and post-intervention, anthropometrics, body composition, systemic inflammation (high-sensitivity C-reactive protein, tumor necrosis factor-α, and interleukin 6), fasting glucose, insulin and homeostasis model assessment-insulin resistance (HOMA-IR) were determined. (3) Results: Subjects had a mean age of 67 years (SD = 5.3) and were mostly women (88%). The PA plus weight loss group lost more total and visceral fat than the PA group (-4.0% vs. +0.6% and -4.1% vs. +3.7%, respectively, p < 0.01 for both). Changes in inflammation and glucose metabolism were similar between groups post-intervention. Within the PA plus weight loss group only, serum insulin and HOMA-IR decreased significantly. (4) Conclusions: PA combined with weight loss can decrease total and visceral fat mass and improve insulin sensitivity, confirming that these cancer- and chronic disease-related risk factors are influenced by relatively modest lifestyle changes in the short term.
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Exercício Físico/fisiologia , Osteoartrite/terapia , Sobrepeso/terapia , Redução de Peso/fisiologia , Programas de Redução de Peso/métodos , Negro ou Afro-Americano , Idoso , Biomarcadores/sangue , Glicemia/análise , Composição Corporal , Índice de Massa Corporal , Doença Crônica/prevenção & controle , Dieta Redutora/métodos , Terapia por Exercício/métodos , Jejum/sangue , Feminino , Humanos , Inflamação , Mediadores da Inflamação/sangue , Insulina/sangue , Resistência à Insulina , Gordura Intra-Abdominal/fisiopatologia , Estilo de Vida , Masculino , Neoplasias/etiologia , Neoplasias/prevenção & controle , Obesidade/sangue , Obesidade/complicações , Obesidade/terapia , Osteoartrite/sangue , Osteoartrite/complicações , Sobrepeso/sangue , Sobrepeso/complicações , Fatores de Risco , Resultado do TratamentoRESUMO
INTRODUCTION: Acute pancreatitis (AP) is a healthcare challenge with considerable mortality. Treatment is limited to supportive care, highlighting the need to investigate disease drivers and prognostic markers. Activin A is an established mediator of inflammatory responses, and its serum levels correlate with AP severity. We hypothesized that activin A is independent of body mass index (BMI) and is a targetable promoter of the AP inflammatory response. METHODS: We assessed whether BMI and serum activin A levels are independent markers to determine disease severity in a cohort of patients with AP. To evaluate activin A inhibition as a therapeutic, we used a cerulein-induced murine model of AP and treated mice with activin A-specific neutralizing antibody or immunoglobulin G control, both before and during the development of AP. We measured the production and release of activin A by pancreas and macrophage cell lines and observed the activation of macrophages after activin A treatment. RESULTS: BMI and activin A independently predicted severe AP in patients. Inhibiting activin A in AP mice reduced disease severity and local immune cell infiltration. Inflammatory stimulation led to activin A production and release by pancreas cells but not by macrophages. Macrophages were activated by activin A, suggesting activin A might promote inflammation in the pancreas in response to injury. DISCUSSION: Activin A provides a promising therapeutic target to interrupt the cycle of inflammation and tissue damage in AP progression. Moreover, assessing activin A and BMI in patients on hospital admission could provide important predictive measures for screening patients likely to develop severe disease.
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Ativinas/metabolismo , Anti-Inflamatórios/farmacologia , Pâncreas/patologia , Pancreatite/diagnóstico , Índice de Gravidade de Doença , Ativinas/antagonistas & inibidores , Ativinas/sangue , Ativinas/imunologia , Animais , Anti-Inflamatórios/uso terapêutico , Biomarcadores/sangue , Biomarcadores/metabolismo , Índice de Massa Corporal , Linhagem Celular , Ceruletídeo/administração & dosagem , Ceruletídeo/toxicidade , Estudos de Coortes , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Feminino , Humanos , Ativação de Macrófagos/imunologia , Macrófagos , Camundongos , Pâncreas/efeitos dos fármacos , Pâncreas/imunologia , Pancreatite/sangue , Pancreatite/tratamento farmacológico , Pancreatite/imunologia , Admissão do Paciente , Valor Preditivo dos TestesRESUMO
BACKGROUND: Cachexia occurs in individuals affected by chronic diseases in which systemic inflammation leads to fatigue, debilitation, decreased physical activity and sarcopenia. The pathogenesis of cachexia-associated sarcopenia is not fully understood. OBJECTIVES: The aim of this systematic review is to summarize the current evidence on genes expressed in the skeletal muscles of humans with chronic disease-associated cachexia and/or sarcopenia (cases) compared to controls and to assess the strength of such evidence. METHODS: We searched PubMed, EMBASE and CINAHL using three concepts: cachexia/sarcopenia and associated symptoms, gene expression, and skeletal muscle. RESULTS: Eighteen genes were studied in at least three research articles, for a total of 27 articles analyzed in this review. Participants were approximately 60 years of age and majority male; sample size was highly variable. Use of comparison groups, matching criteria, muscle biopsy location, and definitions of cachexia and sarcopenia were not homogenous. None of the studies fulfilled all four criteria used to assess the quality of molecular analysis, with only one study powered on the outcome of gene expression. FOXO1 was the only gene significantly increased in cases versus healthy controls. No study found a significant decrease in expression of genes involved in autophagy, apoptosis or inflammation in cases versus controls. Inconsistent or non-significant findings were reported for genes involved in protein degradation, muscle differentiation/growth, insulin/insulin growth factor-1 or mitochondrial transcription. CONCLUSION: Currently available evidence on gene expression in the skeletal muscles of humans with chronic disease-associated cachexia and/or sarcopenia is not powered appropriately and is not homogenous; therefore, it is difficult to compare results across studies and diseases.
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Caquexia/genética , Expressão Gênica , Músculo Esquelético/metabolismo , Sarcopenia/genética , Caquexia/metabolismo , Caquexia/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/patologia , Sarcopenia/metabolismo , Sarcopenia/patologiaRESUMO
OBJECTIVES: The aim of this study was to determine the effect of digested whole human milk (HM; first sample available after birth from mothers of premature infants) on inflammation, oxidative stress, and cytotoxicity in Caco-2 human intestinal epithelial cells stimulated with lipopolysaccharides or tumor necrosis factor (TNF) to mimic the potential in vivo insults facing the premature infant's gastrointestinal tract. METHODS: Fully differentiated Caco-2 cells were exposed to digested HM (nâ=â10; samples from 10 different individuals) before stimulation with lipopolysaccharides, TNF, or no stimulation overnight. Inflammation was determined by production of interleukin-8, oxidative stress by levels of F2-isoprostane, and cytotoxicity by released lactate dehydrogenase. RESULTS: HM significantly suppressed interleukin-8 production and cytotoxicity in TNF-stimulated cells, while also suppressing cell death under baseline conditions. Individual HM samples differed widely in their ability to modulate cellular responses. CONCLUSIONS: Results from this study provide evidence that digested HM can reduce both an exaggerated inflammatory response and intestinal damage that contribute to the pathogenesis of necrotizing enterocolitis.
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Morte Celular/imunologia , Enterocolite Necrosante/prevenção & controle , Doenças do Prematuro/prevenção & controle , Recém-Nascido Prematuro/imunologia , Inflamação/prevenção & controle , Mucosa Intestinal/imunologia , Leite Humano/imunologia , Biomarcadores/metabolismo , Células CACO-2 , Enterocolite Necrosante/etiologia , Enterocolite Necrosante/imunologia , Enterocolite Necrosante/metabolismo , Humanos , Recém-Nascido , Recém-Nascido Prematuro/metabolismo , Doenças do Prematuro/etiologia , Doenças do Prematuro/imunologia , Doenças do Prematuro/metabolismo , Inflamação/etiologia , Inflamação/imunologia , Inflamação/metabolismo , Mucosa Intestinal/metabolismo , Lipopolissacarídeos , Leite Humano/metabolismo , Estresse Oxidativo/imunologia , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Purpose African American women with breast cancer have higher cancer-specific and overall mortality rates. Obesity is common among African American women and contributes to breast cancer progression and numerous chronic conditions. Weight loss interventions among breast cancer survivors positively affect weight, behavior, biomarkers, and psychosocial outcomes, yet few target African Americans. This article examines the effects of Moving Forward, a weight loss intervention for African American breast cancer survivors (AABCS) on weight, body composition, and behavior. Patients and Methods Early-stage (I-III) AABCS were randomly assigned to a 6-month interventionist-guided (n = 125) or self-guided (n = 121) weight loss program supporting behavioral changes to promote a 5% weight loss. Anthropometric, body composition, and behavioral data were collected at baseline, postintervention (6 months), and follow-up (12 months). Descriptive statistics and mixed models analyses assessed differences between groups over time. Results Mean (± standard deviation) age, and body mass index were 57.5 (± 10.1) years and 36.1 (± 6.2) kg/m2, respectively, and 82% had stage I or II breast cancer. Both groups lost weight. Mean and percentage of weight loss were greater in the guided versus self-guided group (at 6 months: 3.5 kg v 1.3kg; P < .001; 3.6% v 1.4%; P < .001, respectively; at 12 months: 2.7 kg v 1.6 kg; P < .05; 2.6% v 1.6%; P < .05, respectively); 44% in the guided group and 19% in the self-guided group met the 5% goal. Body composition and behavioral changes were also greater in the interventionist-guided group at both time points. Conclusion The study supports the efficacy of a community-based interventionist-guided weight loss program targeting AABCS. Although mean weight loss did not reach the targeted 5%, the mean loss of > 3% at 6 months is associated with improved health outcomes. Affordable, accessible health promotion programs represent a critical resource for AABCS.
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Negro ou Afro-Americano/psicologia , Neoplasias da Mama/etnologia , Neoplasias da Mama/terapia , Obesidade/terapia , Sobreviventes/psicologia , Programas de Redução de Peso/métodos , Neoplasias da Mama/complicações , Neoplasias da Mama/patologia , Feminino , Comportamentos Relacionados com a Saúde/etnologia , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Obesidade/complicaçõesRESUMO
Communication among cells (also known as cross-talk) plays a prominent role in the current knowledge of the pathophysiology of cancer and of cancer-associated conditions such as paraneoplastic syndromes and cachexia that are responsible for much of cancer's morbidity and mortality. Yet, biomedical scientists lack an explicit unifying frame that places this exchange of molecular information at the core of their understanding of cancer as a systemic disease. Propaganda is a type of information that aims at misleading, a form of communication intended primarily to serve the messenger. The biased molecular cross-talk between cancer and non-cancer cells can be considered as a form of biological propaganda. I here propose cancer is a propagandist as a metaphor that may serve as a unifying frame to interpret both cancer and cancer-associated syndromes under the same communication-based concept and may thus serve to bring together research that is currently compartmentalized under separate disciplines.
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Caquexia , Neoplasias/fisiopatologia , Síndromes Paraneoplásicas , HumanosRESUMO
Visceral adipose tissue (VAT) but not subcutaneous adipose tissue (SAT) is associated with obesity-related diseases including colorectal cancer (CRC). Superficial SAT (SSAT) and deep SAT (DSAT), components of SAT, also appear to independently influence disease risk. These abdominal adipose tissues (AATs) are not extensively studied in connection with CRC and have not been explored in the United States despite known racial variations in body composition. We conducted a case-control study that compared associations between AAT with CRC risk and race of African-American (AA) and non-Hispanic white (NHW) men with incident CRC matched by age, body mass index, and race (N = 158, 79/group). Cross-sectional computed tomography images were used for assessment of AAT. Overall cases and controls had similar VAT areas (140 ± 192 vs 149 ± 152 cm2, P-value = 0.93); however, cases had lower SSAT than controls (88 ± 39 vs 112 ± 65 cm2, P < 0.01). Among controls, AA had significantly lower VAT (114 ± 168 vs 180 ± 167, P < 0.01) than NHW. Conditional logistic regression revealed that AA men with greater SSAT had lower odds for CRC (odds ratio [OR]: 0.24, 95% confidence interval [CI] 0.07-0.85). Our findings indicate that VAT does vary between cases and controls by race; however, this variation is not a risk factor for CRC. The negative association between CRC and SSAT in AA men warrants further investigation.
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Neoplasias Colorretais/etnologia , Neoplasias Colorretais/etiologia , Gordura Intra-Abdominal/fisiopatologia , Adulto , Negro ou Afro-Americano , Composição Corporal , Estudos de Casos e Controles , Humanos , Modelos Logísticos , Pessoa de Meia-Idade , Obesidade Abdominal/complicações , Fatores de Risco , População BrancaRESUMO
Gestational weight gain (GWG) is an important modifiable factor known to influence fetal outcomes including birth weight and adiposity. Unlike behaviors such as smoking and alcohol consumption, the effect of GWG throughout pregnancy on fetal development and other outcomes has not been extensively studied. The aim of this study was to investigate the relationship of GWG with endocrine factors such as adiponectin, leptin, and C-reactive protein which may be associated with inflammatory response, fetal growth, and adiposity later in life. Data were obtained from the Ulm Birth Cohort Study (UBCS) and the Ulm SPATZ Health Study, two methodologically similar birth cohort studies including newborns and their mothers recruited from 11/2000-11/2001 and 04/2012-05/2013. In the two included birth cohorts we consistently observed statistically significant positive associations between GWG beginning as early as the second trimester with fetal cord blood leptin and stronger association beginning as early as the first trimester with post-delivery maternal serum leptin. Total weight gain exceeding commonly accepted recommended guidelines was consistently associated with higher leptin levels in both cord blood and post-delivery maternal serum. These results suggest a potential pathomechanistic link between fetal environment and surrogate markers of long-term health.
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Adiponectina/sangue , Proteína C-Reativa/metabolismo , Peso Fetal , Leptina/sangue , Complicações na Gravidez/sangue , Aumento de Peso , Adiposidade , Adulto , Biomarcadores/sangue , Peso ao Nascer , Estudos de Casos e Controles , Feminino , Humanos , Recém-Nascido , Masculino , Gravidez , Complicações na Gravidez/epidemiologiaRESUMO
BACKGROUND: Fatigue is highly prevalent after hematopoietic stem cell transplantation (HCT). It has been described as intense and may last for years following treatment. OBJECTIVE: The aim of this study is to compare fatigue, physical activity, sleep, emotional distress, cognitive function, and biological measures in HCT survivors with persistent fatigue (n = 25) with age- and gender-matched healthy controls with occasional tiredness (n = 25). METHODS: Data were collected using (a) objective, real-time assessments of physical activity and sleep over 7 days; (b) patient-reported fatigue assessments; (c) computerized objective testing of cognitive functioning; and (d) biological measures. Differences between groups were examined using multivariate analysis of variance. RESULTS: Survivors of HCT reported increased physical (P < .001), mental (P < .001), and overall (P < .001) fatigue as well as increased anxiety (P < .05) and depression (P < .01) compared with healthy controls. Red blood cell (RBC) levels were significantly lower in HCT survivors (P < .001). Levels of RBC for both groups, however, were in the normal range. Tumor necrosis factor-α (P < .001) and interleukin-6 (P < .05) levels were significantly higher in HCT survivors. CONCLUSIONS: Persistent fatigue in HCT survivors compared with healthy controls with occasional tiredness is accompanied by increased anxiety and depression along with decreased RBC counts. Elevated tumor necrosis factor-α and interleukin-6 levels may be important biomarkers. IMPLICATIONS FOR PRACTICE: This study provides preliminary support for the conceptualization of fatigue as existing on a continuum, with tiredness anchoring one end and exhaustion the other. Persistent fatigue experienced by HCT survivors is more severe than the occasional tiredness of everyday life.
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Fadiga/epidemiologia , Transplante de Células-Tronco Hematopoéticas/psicologia , Sobreviventes/psicologia , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sobreviventes/estatística & dados numéricosRESUMO
OBJECTIVE: Studies were performed to uncover the significance of obesity in rheumatoid arthritis (RA) and preclinical models. METHODS: Preclinical arthritis models were used to examine the impact of obesity on disease onset and remission. Conditioned media from RA adipose tissues were used to investigate the mechanism contributing to joint neutrophil influx and M1 macrophage differentiation observed in early and remission phases of arthritis. RESULTS: We report that mice fed with high fat diet (HFD) have an earlier onset of collagen-induced arthritis (CIA) compared with mice on regular diet. However, the differences in CIA joint swelling between the two diet groups are lost once disease is established. We found that early arthritis triggered by obesity is due to elevated joint MIP2/interleukin-8 levels detected in CIA as well as in the RA and mouse adipose tissues and the effect of this chemokine on neutrophil recruitment. Although active disease progression is similarly affected in both diet groups, arthritis resolution is accelerated in lean mice while joint inflammation is sustained in obese mice. We document that HFD can prolong toll-like receptor (TLR)4-induced arthritis by increasing joint monocyte migration and further remodelling the recruited cells into M1 macrophages. Consistently, we show that adipose condition media can transform RA and wild-type naïve myeloid cells into M1 macrophages; however, this function is impaired by TLR4 blockade or deficiency. CONCLUSIONS: We conclude that despite established disease being unaffected by obesity, the early and the resolution phases of RA are impacted by obesity through different mechanisms.
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Tecido Adiposo/metabolismo , Artrite Reumatoide/metabolismo , Citocinas/metabolismo , Articulações/metabolismo , Obesidade/metabolismo , Receptor 4 Toll-Like/metabolismo , Animais , Artrite Reumatoide/induzido quimicamente , Artrite Reumatoide/patologia , Movimento Celular , Quimiocina CXCL2/metabolismo , Colágeno , Gorduras na Dieta/administração & dosagem , Modelos Animais de Doenças , Interleucina-8/metabolismo , Articulações/patologia , Lipopolissacarídeos , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBA , Neutrófilos/fisiologia , Transdução de SinaisRESUMO
BACKGROUND: Breast cancer survival rates are significantly lower among African-American women compared to white women. In addition, African-American women with breast cancer are more likely than white women to die from co-morbid conditions. Obesity is common among African-American women, and it contributes to breast cancer progression and the development and exacerbation of many weight-related conditions. Intervening upon obesity may decrease breast cancer and all-cause mortality among African-American breast cancer survivors. METHODS/DESIGN: Moving Forward is a weight loss intervention being evaluated in a randomized trial with a projected sample of 240 African American breast cancer survivors. Outcomes include body mass index, body composition, waist:hip ratio, and behavioral, psychosocial and physiological measures. Survivors are randomized to either a 6-month guided weight loss intervention that involves twice weekly classes and text messaging or a self-guided weight loss intervention based on the same materials offered in the guided program. The guided intervention is being conducted in partnership with the Chicago Park District at park facilities in predominantly African-American neighborhoods in Chicago. Recruitment strategies include direct contact to women identified in hospital cancer registries, as well as community-based efforts. Data collection occurs at baseline, post-intervention (6 months) and at a 12-month follow-up. DISCUSSION: This study evaluates a community-based, guided lifestyle intervention designed to improve the health of African-American breast cancer survivors. Few studies have addressed behavioral interventions in this high-risk population. If successful, the intervention may help reduce the risk for breast cancer recurrence, secondary cancers, and co-morbid conditions, as well as improve quality of life. TRIAL REGISTRATION: U.S. Clinicaltrials.gov number: NCT02482506, April 2015.
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Negro ou Afro-Americano/psicologia , Neoplasias da Mama/mortalidade , Sobreviventes/psicologia , Neoplasias da Mama/psicologia , Chicago/etnologia , Feminino , Humanos , Qualidade de Vida , Distribuição Aleatória , Resultado do Tratamento , Redução de PesoRESUMO
OBJECTIVE: In this study, the associations between vitamin D, insulin sensitivity, and inflammation and their relationships with adipose tissue expression of vitamin D receptor (VDR) and inflammatory markers in women with morbid obesity were determined. METHODS: An oral glucose tolerance test prior to surgery was completed by healthy premenopausal women (n = 76) seeking bariatric surgery. Abdominal subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) were collected during surgery. RESULTS: Approximately, 70% of our subjects were vitamin D sufficient or optimal, and 80% had normal glucose tolerance. No significant association between serum 25-hydroxyvitamin D [25(OH)D] with circulating inflammatory markers or insulin sensitivity was identified. In subjects with waist circumference of <139 cm (n = 42), log25(OH)D positively predicted VAT logIL-6 mRNA expression (P = 0.003). LogVDR expression was positively correlated with the expression of inflammatory markers in both SAT (logIL-1ß mRNA: r = 0.95, P < 0.0001; logTNF mRNA: r = 0.82, P < 0.0001) and VAT (logIL-1ß mRNA: r = 0.89, P < 0.0001; logTNF mRNA: r = 0.75, P < 0.0001). VAT logVDR expression positively predicted logHOMA-IR in non-African American subjects (P = 0.05). CONCLUSIONS: The beneficial effects of vitamin D on inflammation and insulin sensitivity were not supported by our findings. VDR does not appear to possess a protective effect in adipose tissue.
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Resistência à Insulina , Obesidade Mórbida/metabolismo , Vitamina D/análogos & derivados , Adulto , Feminino , Teste de Tolerância a Glucose , Humanos , Inflamação/metabolismo , Gordura Intra-Abdominal/metabolismo , Pessoa de Meia-Idade , Pré-Menopausa , Vitamina D/metabolismoRESUMO
Acute pancreatitis (AP), although most often a mild and self-limiting inflammatory disease, worsens to a characteristically necrotic severe acute pancreatitis (SAP) in about 20% of cases. Obesity, affecting more than one-third of American adults, is a risk factor for the development of SAP, but the exact mechanism of this association has not been identified. Coincidental with chronic low-grade inflammation, activation of the nucleotide-binding domain, leucine-rich containing family, pyrin-domain containing 3 (NLRP3) inflammasome increases with obesity. Lean mice genetically deficient in specific components of the NLRP3 inflammasome are protected from experimentally induced AP, indicating a direct involvement of this pathway in AP pathophysiology. We hypothesized that inhibition of the NLRP3 inflammasome with the sulfonylurea drug glyburide would reduce disease severity in obese mice with cerulein-induced SAP. Treatment with glyburide led to significantly reduced relative pancreatic mass and water content and less pancreatic damage and cell death in genetically obese ob/ob mice with SAP compared with vehicle-treated obese SAP mice. Glyburide administration in ob/ob mice with cerulein-induced SAP also resulted in significantly reduced serum levels of interleukin 6, lipase, and amylase and led to lower production of lipopolysaccharide-stimulated interleukin 1ß release in cultured peritoneal cells, compared with vehicle-treated ob/ob mice with SAP. Together, these data indicate involvement of the NLRP3 inflammasome in obesity-associated SAP and expose the possible utility of its inhibition in prevention or treatment of SAP in obese individuals.
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Proteínas de Transporte/metabolismo , Glibureto/farmacologia , Hipoglicemiantes/farmacologia , Pancreatite/induzido quimicamente , Amilases/sangue , Amilases/metabolismo , Animais , Proteínas de Transporte/antagonistas & inibidores , Proteínas de Transporte/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Interleucina-1beta/metabolismo , Interleucina-6/sangue , Interleucina-6/metabolismo , Lipase/sangue , Lipase/metabolismo , Macrófagos Peritoneais/efeitos dos fármacos , Macrófagos Peritoneais/metabolismo , Camundongos , Camundongos Obesos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Pancreatite/metabolismo , Pancreatite/patologiaRESUMO
BACKGROUND: Increased cellular iron exposure is associated with colorectal cancer (CRC) risk. Hepcidin, a liver peptide hormone, acts as the primary regulator of systemic iron status by blocking iron release from enterocytes into plasma. Concentrations are decreased during low iron status and increased during inflammation. The role of hepcidin and the factors influencing its regulation in CRC remains largely unknown. This study explored systemic and tumor level iron regulation in men with CRC. METHODS: The participants were 20 CRC cases and 20 healthy control subjects. Colonic tissue (adenocarcinoma [cases] healthy mucosa [controls]) was subjected to quantitative PCR (hepcidin, iron transporters and IL-6) and Perls' iron staining. Serum was analyzed using ELISA for hepcidin, iron status (sTfR) and inflammatory markers (CRP, IL-6, TNF-α). Anthropometrics, dietary iron intake and medical history were obtained. RESULTS: Cases and controls were similar in demographics, medication use and dietary iron intake. Systemically, cases compared to controls had lower iron status (sTfR: 21.6 vs 11.8 nmol/L, p < 0.05) and higher marker of inflammation (CRP: 8.3 vs 3.4 µg/mL, p < 0.05). Serum hepcidin was mildly decreased in cases compared to controls; however, it was within the normal range for both groups. Within colonic tissue, 30% of cases (6/20) presented iron accumulation compared to 5% of controls (1/20) (χ(2) = 5.0; p < 0.05) and higher marker of inflammation (IL-6: 9.4-fold higher compared to controls, p < 0.05). Presence of adenocarcinoma iron accumulation was associated with higher serum hepcidin (iron accumulation group 80.8 vs iron absence group 22.0 ng/mL, p < 0.05). CONCLUSIONS: While CRC subjects had serum hepcidin concentrations in the normal range, it was higher given their degree of iron restriction. Inappropriately elevated serum hepcidin may reduce duodenal iron absorption and further increase colonic adenocarcinoma iron exposure. Future clinical studies need to assess the appropriateness of dietary iron intake or iron supplementation in patients with CRC.
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Production of Annexin A1 (ANXA1), a protein that mediates the anti-inflammatory action of glucocorticoids, is altered in obesity, but its role in modulation of adiposity has not yet been investigated. The objective of this study was to investigate modulation of ANXA1 in adipose tissue in murine models of obesity and to study the involvement of ANXA1 in diet-induced obesity in mice. Significant induction of ANXA1 mRNA was observed in adipose tissue of both C57BL6 and Balb/c mice with high fat diet (HFD)-induced obesity versus mice on chow diet. Upregulation of ANXA1 mRNA was independent of leptin or IL-6, as demonstrated by use of leptin-deficient ob/ob mice and IL-6 KO mice. Compared to WT mice, female Balb/c ANXA1 KO mice on HFD had increased adiposity, as indicated by significantly elevated body weight, fat mass, leptin levels, and adipocyte size. Whereas Balb/c WT mice upregulated expression of enzymes involved in the lipolytic pathway in response to HFD, this response was absent in ANXA1 KO mice. A significant increase in fasting glucose and insulin levels as well as development of insulin resistance was observed in ANXA1 KO mice on HFD compared to WT mice. Elevated plasma corticosterone levels and blunted downregulation of 11-beta hydroxysteroid dehydrogenase type 1 in adipose tissue was observed in ANXA1 KO mice compared to diet-matched WT mice. However, no differences between WT and KO mice on either chow or HFD were observed in expression of markers of adipose tissue inflammation. These data indicate that ANXA1 is an important modulator of adiposity in mice, with female ANXA1 KO mice on Balb/c background being more susceptible to weight gain and diet-induced insulin resistance compared to WT mice, without significant changes in inflammation.