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1.
JAMA Oncol ; 2022 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-35511155

RESUMO

Importance: In the past 4 years, the American Cancer Society and the US Preventive Services Task Force updated recommendations to initiate colorectal cancer (CRC) screening at 45 years of age to address the increasing incidence of CRC among adults younger than 50 years. However, empirical evidence evaluating the potential benefits of screening in younger populations is scant. Objective: To examine the association between endoscopy initiation at different ages and risk of CRC among US women. Design, Setting, and Participants: This prospective cohort study used data from the Nurses' Health Study II, which included US female health professionals followed up from 1991 through 2017. Data analysis was performed from August 2020 to June 2021. Exposure: Age at initiation of sigmoidoscopy or colonoscopy for screening (routine screening or because of family history) or symptoms. Main Outcomes and Measures: Incident CRC, confirmed by medical records, pathology reports, and the National Death Index. Cumulative incidence of CRC in each group was estimated with age as the time scale, and the absolute risk reduction associated with endoscopy initiation at different ages through 60 years was calculated. Cox proportional hazards regression was used to calculate hazard ratios (HRs) and 95% CIs, stratified by age and calendar year of questionnaire cycle and adjusted for CRC risk factors in the multivariable models. Results: Among 111 801 women aged 26 to 46 years (median, 36 years) at enrollment, 519 incident CRC cases were documented over 26 years, encompassing 2 509 358 person-years of follow-up. In the multivariable analysis, compared with no endoscopy, undergoing endoscopy was associated with a significantly lower risk of incident CRC for age at initiation before 45 years (HR, 0.37; 95% CI, 0.26-0.53), 45 to 49 years (HR, 0.43; 95% CI, 0.29-0.62), 50 to 54 years (HR, 0.47; 95% CI, 0.35-0.62), and 55 years or older (HR, 0.46; 95% CI, 0.30-0.69). The absolute reduction in the estimated cumulative incidence of CRC through 60 years of age was 72 per 100 000 persons for initiation of endoscopy at 45 to 49 years of age vs 50 to 54 years of age. Compared with no endoscopy, initiation of endoscopy before 50 years of age was also associated with a reduced risk of CRC diagnosed before 55 years of age (<45 years: HR, 0.45 [95% CI, 0.29-0.70]; 45-49 years: HR, 0.43 [95% CI, 0.24-0.76]). Conclusions and Relevance: In this cohort study, compared with no endoscopy, initiation of endoscopy before 50 years of age was associated with a reduced risk of CRC, including CRC diagnosed before 55 years of age. Screening before 50 years of age was associated with greater absolute reduction in CRC risk compared with initiation of CRC screening at 50 years of age or later.

2.
Investig Clin Urol ; 63(3): 350-358, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35534220

RESUMO

PURPOSE: Our purpose was to verify the effects of atorvastatin (ATO) on prostate cancer (PCa) proliferation, apoptosis, invasion, and metastasis and to further explore the drug's mechanism of action. MATERIALS AND METHODS: We used cell counting kit-8 (CCK8) and clone formation experiments to study the effect of ATO on the proliferation of PC3 cells. Flow cytometry and Hoechst 33342 staining were used to detect cell apoptosis. Cell migration and invasion were detected through wound healing experiments and transwell experiments. Western blotting was applied to detect apoptosis-related proteins (BAX, Bcl-2, PARP, and Caspase-3), epithelial-mesenchymal transformation (EMT) proteins, and matrix metalloproteinase (MMP) expression. A mouse xenograft tumor model was established, and tumor volume and weight were determined. The expression levels of the above-mentioned proteins were determined through western blot. RESULTS: ATO inhibited PC-3 cell proliferation and promoted cell apoptosis in a dose-dependent manner. ATO significantly up-regulated the expression of BAX, PARP, and Caspase-3 and inhibited the expression of Bcl-2. Wound healing and transwell experiments showed that ATO inhibited invasion and metastasis in PC-3 cells, possibly because ATO could inhibit the EMT and the expression of MMPs in PC-3 cells. Studies in nude mice showed that ATO significantly reduced tumor volume and weight; the expression levels of related proteins were consistent with the in vitro results. CONCLUSIONS: ATO inhibits the occurrence and development of PCa and regulates the migration and invasion of PCa cells by inhibiting the EMT and MMPs.


Assuntos
Transição Epitelial-Mesenquimal , Neoplasias da Próstata , Animais , Atorvastatina/farmacologia , Atorvastatina/uso terapêutico , Caspase 3/farmacologia , Caspase 3/uso terapêutico , Linhagem Celular Tumoral , Proliferação de Células , Humanos , Masculino , Metaloproteinases da Matriz , Camundongos , Camundongos Nus , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Neoplasias da Próstata/patologia , Proteína X Associada a bcl-2/metabolismo , Proteína X Associada a bcl-2/farmacologia
3.
Int J Cancer ; 2022 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-35383926

RESUMO

Diabetes is an established risk factor for colorectal cancer. However, colorectal cancer is a heterogeneous disease and it is not well understood whether diabetes is more strongly associated with some tumor molecular subtypes than others. A better understanding of the association between diabetes and colorectal cancer according to molecular subtypes could provide important insights into the biology of this association. We used data on lifestyle and clinical characteristics from the Colorectal Cancer Family Registry (CCFR) and the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), including 9756 colorectal cancer cases (with tumor marker data) and 9985 controls, to evaluate associations between reported diabetes and risk of colorectal cancer according to molecular subtypes. Tumor markers included BRAF and KRAS mutations, microsatellite instability and CpG island methylator phenotype. In the multinomial logistic regression model, comparing colorectal cancer cases to cancer-free controls, diabetes was positively associated with colorectal cancer regardless of subtype. The highest OR estimate was found for BRAF-mutated colorectal cancer, n = 1086 (ORfully adj : 1.67, 95% confidence intervals [CI]: 1.36-2.05), with an attenuated association observed between diabetes and colorectal cancer without BRAF-mutations, n = 7959 (ORfully adj : 1.33, 95% CI: 1.19-1.48). In the case only analysis, BRAF-mutation was differentially associated with diabetes (Pdifference  = .03). For the other markers, associations with diabetes were similar across tumor subtypes. In conclusion, our study confirms the established association between diabetes and colorectal cancer risk, and suggests that it particularly increases the risk of BRAF-mutated tumors.

4.
Am J Clin Nutr ; 2022 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-35470384

RESUMO

BACKGROUND: Recent preclinical research strongly suggests that dietary sugars can enhance colorectal tumorigenesis by direct action, particularly in the proximal colon that unabsorbed fructose reaches. OBJECTIVES: We aimed to examine long-term consumption of sugar-sweetened beverages (SSBs) and total fructose in relation to incidence and mortality of colorectal cancer (CRC) by anatomic subsite. METHODS: We followed 121,111 participants from 2 prospective US cohort studies, the Nurses' Health Study (1984-2014) and Health Professionals Follow-Up Study (1986-2014), for incident CRC and related death. Cox proportional hazards regression was used to compute HRs and 95% CIs. RESULTS: During follow-up, we documented 2733 incident cases of CRC with a known anatomic location, of whom 901 died from CRC. Positive associations of SSB and total fructose intakes with cancer incidence and mortality were observed in the proximal colon but not in the distal colon or rectum (Pheterogeneity ≤ 0.03). SSB consumption was associated with a statistically significant increase in the incidence of proximal colon cancer (HR per 1-serving/d increment: 1.18; 95% CI: 1.03, 1.34; Ptrend = 0.02) and a more pronounced elevation in the mortality of proximal colon cancer (HR: 1.39; 95% CI: 1.13, 1.72; Ptrend = 0.002). Similarly, total fructose intake was associated with increased incidence and mortality of proximal colon cancer (HRs per 25-g/d increment: 1.18; 95% CI: 1.03, 1.35; and 1.42; 95% CI: 1.12, 1.79, respectively). Moreover, SSB and total fructose intakes during the most recent 10 y, rather than those from a more distant period, were associated with increased incidence of proximal colon cancer. CONCLUSIONS: SSB and total fructose consumption were associated with increased incidence and mortality of proximal colon cancer, particularly during later stages of tumorigenesis.

5.
Int J Epidemiol ; 2022 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-35388877

RESUMO

BACKGROUND: The link between oral diseases and mortality remains under-explored. We aimed to evaluate the associations between tooth count, untreated caries and risk of all-cause and cause-specific mortality. METHODS: Data on 24 029 adults from the National Health and Nutrition Examination Survey 1988-94/1999-2010, with mortality linkage to the National Death Index to 31 December 2015, were analysed. Baseline total number of permanent teeth and any untreated caries were assessed by trained dental professionals. RESULTS: During up to 27 years of follow-up, 5270 deaths occurred. Fewer permanent teeth were associated with higher all-cause mortality, including heart disease and cancer mortality (all P <0.05 for trend) but not cerebrovascular disease mortality. For every 10 teeth missing, the multivariable-adjusted hazard ratios (HRs) were 1.13 (95% CI: 1.08 to 1.18) for all-cause, 1.16 (95% CI: 1.05, 1.29) for heart disease and 1.19 (95% CI: 1.09, 1.29) for cancer mortality. Untreated caries was associated with increased all-cause (HR: 1.26, 95% CI: 1.15, 1.39) and heart disease mortality (HR: 1.48, 95% CI: 1.17, 1.88) but not cerebrovascular disease/cancer mortality, after adjusting for tooth count, periodontitis and sociodemographic/lifestyle factors. Compared with those without untreated caries and with 25-28 teeth, individuals with untreated caries and 1-16 teeth had a 53% increased risk of all-cause mortality (HR: 1.53, 95% CI: 1.27, 1.85) and 96 % increased risk of heart disease mortality (HR: 1.96, 95% CI: 1.28, 3.01). CONCLUSIONS: In nationally representative cohorts, fewer permanent teeth and untreated caries were associated with all-cause and heart disease mortality. Fewer teeth were also associated with higher cancer mortality.

6.
Artigo em Inglês | MEDLINE | ID: mdl-35348611

RESUMO

Although aspirin has been considered a promising agent for prevention of colorectal cancer (CRC), recent data suggest a lack of benefit among older individuals. Whether some individuals with higher risk of CRC may benefit from aspirin remains unknown. We used a 95-variant CRC polygenic risk score (PRS) to explore the association between genetic susceptibility to CRC and aspirin use in a prospective study of 12,609 individuals of European descent aged {greater than or equal to} 70 years, enrolled in the ASPREE (ASPirin in Reducing Events in the Elderly) double-blinded, placebo-controlled randomized trial (RCT). Cox proportional hazards models were used to assess the association of aspirin use on CRC, as well as the interaction between the PRS and aspirin treatment on CRC. Over a median of 4.7 years follow-up, 143 participants were diagnosed with incident CRC. Aspirin assignment was not associated with incidence of CRC overall (hazard ratio [HR]=0.94, 95% confidence interval (CI) 0.68-1.30) or within strata of PRS (p for interaction=0.97). However, the PRS was associated with an increased risk of CRC (HR=1.28 per standard deviation [SD], 95% CI 1.09-1.51). Individuals in the top quintile of the PRS distribution had an 85% higher risk compared with individuals in the bottom quintile (HR=1.85, 95% CI 1.08-3.15). In a prospective RCT of older individuals, a PRS is associated with incident CRC risk, but aspirin use was not associated with a reduction of incident CRC, regardless of baseline genetic risk.

7.
Ann Transl Med ; 10(3): 134, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35284558

RESUMO

Background: To explore the contribution of type 2 diabetes mellitus (T2DM) to hypothalamic inflammation and depressive disorders in young patients with obesity. Methods: According to the diagnostic criteria for T2DM, all of patients with obesity were divided into the diabetic and the non-diabetic groups. The severity of depressive disorders was assessed by self-rating depression scale (SDS). The signal intensity (SI) ratio of the T2-weighted phase of the superior hypothalamus/amygdala (H/A) was measured using a quantitative magnetic resonance imaging (MRI) technique to evaluate hypothalamic inflammation. Univariate and multivariate logistic regression analysis was used to find the influencing factors of depressive disorder. The prediction equation's sensitivity and specificity for the depressive disorder were calculated based on the receiver operating characteristic (ROC) curve. Results: In young patients with obesity and diabetes, the incidence of depression is 79.49%, which was much higher than that in patients without diabetes (P<0.001). The SI of the left H/A in young patients with obesity and diabetes is significantly higher than that in non-diabetic patients (P<0.001). The relative risks of depression are fasting blood glucose (FBG) (OR 1.60; CI: 1.26-2.05), HbA1c (OR 1.94; CI: 1.40-2.68) and triglycerides (OR 1.40; CI: 1.03-1.90). Only FBG enters the predictive equation for depressive disorder, with a 52.8% sensitivity and 84.5% specificity. Conclusions: In young diabetic patients with obesity, the incidence of depressive disorder is high, a mechanism possibly related to the left hypothalamus inflammation. Elevated FBG can be an independent predictor of depressive disorder in young patients with obesity.

8.
Ying Yong Sheng Tai Xue Bao ; 33(2): 457-466, 2022 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-35229520

RESUMO

With the intensification of climate change, the frequency, duration and scope of drought have become more and more serious. Exploring the responses of plant photosynthesis to drought and the impacts of meteorological factors on photosynthesis is of great significance to the dealing with drought stress. Solar-induced chlorophyll fluorescence (SIF) based on remote sensing has the potential for early monitoring and accurate assessment of regional vege-tation photosynthesis under drought conditions. Based on the spaceborne SIF information and the standardized precipitation evapotranspiration index (SPEI), we investigated the responses of vegetation photosynthesis to drought and the influence of meteorological factors in the growing season (April to October) of the Loess Plateau during 2001-2017. The results showed that about 87.8% of total areas of the Loess Plateau had a significant positive correlation between SIF and SPEI. Vegetation photosynthesis in semi-arid area was more sensitive to drought and less sensitive in semi-humid area. Different vegetation types had different photosynthetic responses to drought. Grassland had the highest sensitivity to drought with three to four months SPEI time-scale, while forest had the lowest sensiti-vity with three to ten months SPEI time-scale. There was a significant correlation between meteorological factors and SIF. Temperature and precipitation were the most important factors affecting vegetation photosynthesis on the Loess Plateau. Photosynthetically active radiation showed a similar controlling strength to temperature. The impacts of drought and meteorological factors on vegetation photosynthesis were largely determined by differences in drought resistance among ecosystem types and climate regions.


Assuntos
Secas , Ecossistema , China , Clorofila , Fluorescência , Estações do Ano
9.
Molecules ; 27(5)2022 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-35268797

RESUMO

Nur77 is an orphan nuclear receptor that participates in the occurrence and development of a variety of tumors. Many agonists of Nur77 have been reported to have significant anticancer effects. Our previous studies have found that the introduction of bicyclic aromatic rings, such as naphthalyl and quinoline groups, into the N'-methylene position of indoles' Nur77 modulators can effectively improve the anti-tumor activity of the target compounds. Following our previous studies, a series of novel 1-(2-(6-methoxynaphthalen-2-yl)-6-methylnicotinoyl)-4-substituted semicarbazide/thiosemicarbazide derivatives 9a-9w were designed and synthesized in four steps from 6-methoxy-2-acetonaphthone and N-dimethylformamide dimethylacetal. All compounds were characterized by 1H-NMR, 13C-NMR and HRMS, and their anti-tumor activity on various cancer cell lines such as A549, HepG2, HGC-27, MCF-7 and HeLa are also evaluated. From the series of compounds, 9h exhibited the most potent anti-proliferative activity against several cancer cells. Colony formation and cell cycle experiments showed that compound 9h inhibited cell growth and arrested the cell cycle. Additionally, 9h leads to the cleavage of PARP. We initially explored the mechanism of 9h-induced apoptosis and found that compound 9h can upregulate Nur77 expression and triggered Nur77 nuclear export, indicating the occurrence of Nur77-mediated apoptosis. These results suggested that 9h may be a promising anti-tumor leading compound for the further research.


Assuntos
Semicarbazidas
10.
Bioorg Chem ; 120: 105645, 2022 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-35121551

RESUMO

In continuing our study on discovering new Nur77-targeting anti-inflammatory agents with natural skeletons, we combined adamantyl group and hydroxamic acid moiety with flavonoid nucleus, synthesized three series of flavonoid derivatives with a similar structure like CD437, and evaluated their activities against LPS-induced inflammation. Compound B7 was found to be an excellent Nur77 binder (Kd = 3.55 × 10-7 M) and a potent inhibitor of inflammation, which significantly decreased the production of cytokines in vitro, such as NO, IL-6, IL-1ß, and TNF-α, at concentrations of 1.25, 2.5, and 5 µM. Mechanistically, B7 modulated the colocalization of Nur77 at mitochondria and inhibited the lipopolysaccharides (LPS)-induced inflammation via the blockade of NF-κB activation in a Nur77-dependent manner. Additionally, B7 showed in vivo anti-inflammatory activity in the LPS-induced mice model of acute lung injury (ALI). These data suggest that the Nur77-targeting flavonoid derivatives can be particularly useful for further pharmaceutical development for the treatment of inflammatory diseases such as ALI.

11.
J Natl Cancer Inst ; 114(4): 528-539, 2022 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-35026030

RESUMO

BACKGROUND: The incidence of colorectal cancer (CRC) among individuals aged younger than 50 years has been increasing. As screening guidelines lower the recommended age of screening initiation, concerns including the burden on screening capacity and costs have been recognized, suggesting that an individualized approach may be warranted. We developed risk prediction models for early-onset CRC that incorporate an environmental risk score (ERS), including 16 lifestyle and environmental factors, and a polygenic risk score (PRS) of 141 variants. METHODS: Relying on risk score weights for ERS and PRS derived from studies of CRC at all ages, we evaluated risks for early-onset CRC in 3486 cases and 3890 controls aged younger than 50 years. Relative and absolute risks for early-onset CRC were assessed according to values of the ERS and PRS. The discriminatory performance of these scores was estimated using the covariate-adjusted area under the receiver operating characteristic curve. RESULTS: Increasing values of ERS and PRS were associated with increasing relative risks for early-onset CRC (odds ratio per SD of ERS = 1.14, 95% confidence interval [CI] = 1.08 to 1.20; odds ratio per SD of PRS = 1.59, 95% CI = 1.51 to 1.68), both contributing to case-control discrimination (area under the curve = 0.631, 95% CI = 0.615 to 0.647). Based on absolute risks, we can expect 26 excess cases per 10 000 men and 21 per 10 000 women among those scoring at the 90th percentile for both risk scores. CONCLUSIONS: Personal risk scores have the potential to identify individuals at differential relative and absolute risk for early-onset CRC. Improved discrimination may aid in targeted CRC screening of younger, high-risk individuals, potentially improving outcomes.


Assuntos
Neoplasias Colorretais , Detecção Precoce de Câncer , Idoso , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/genética , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Medição de Risco , Fatores de Risco
12.
J Alzheimers Dis ; 86(1): 125-134, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35001890

RESUMO

BACKGROUND: Serum non-high-density lipoprotein-cholesterol (non-HDL-C) levels may be associated with cognitive function. OBJECTIVE: The objective of this study was to evaluate the association between non-HDL-C and cognitive function among American elders. METHODS: We used data from the 2011 to 2014 U.S. National Health and Nutrition Examination Survey (NHANES). A total of 3,001 participants aged over 60 years were enrolled in our analysis. The cognitive function was evaluated with the word learning subtest from the Consortium to Establish a Registry for Alzheimer's disease (CERAD W-L), the Animal Fluency Test (AFT), and the digit symbol substitution test (DSST). We also created a composite cognitive z-score to represent a global cognition. We applied multivariate linear regression analyses to estimate the associations between non-HDL-C levels and all domains of cognitive function. Further, the generalized additive model and the smooth curve were conducted to investigate the dose-response relationship between non-HDL-C and global cognition. RESULTS: Serum non-HDL-C was positively associated with global cognition (ß= 0.20, 95% CI: 0.11, 0.28), AFT score (ß= 0.54, 95% CI: 0.33, 0.76), and DSST score (ß= 1.13, 95% CI: 0.56, 1.69) after fully adjusted. While non-HDL-C was not related to CERAD W-L score. In addition, an inverted U-shape curve was observed in the dose-response relationship between non-HDL-C and global cognition (p for non-linearity < 0.001). CONCLUSION: Serum non-HDL-C is positively and nonlinearly associated with cognitive function among American older adults. Maintaining serum cholesterol levels at an appropriate range may be helpful to the cognitive health of the elderly.


Assuntos
Doença de Alzheimer , Cognição , Idoso , Animais , Colesterol , Estudos Transversais , Humanos , Inquéritos Nutricionais , Estados Unidos/epidemiologia
13.
Clin Transl Gastroenterol ; 13(1): e00437, 2022 01 13.
Artigo em Inglês | MEDLINE | ID: mdl-35029165

RESUMO

INTRODUCTION: Antibiotic use has emerged as a risk factor for colorectal neoplasia and is hypothesized as a contributor to the rising incidence of colorectal cancer under age 50 years or early-onset colorectal cancer (EOCRC). However, the impact of antibiotic use and risk of EOCRC is unknown. METHODS: We conducted a population-based case-control study of CRC among individuals aged ≥18 years in the Epidemiology Strengthened by histoPathology Reports in Sweden (ESPRESSO) cohort (2006-2016). The primary outcome was EOCRC. A secondary outcome was CRC at any age. Incident CRC was pathologically confirmed, and for each, up to 5 population-based controls were matched on age, sex, county of residence, and calendar year. We assessed prescriptions until 6 months before CRC diagnosis. Conditional logistic regression was used to estimate adjusted odds ratios (aORs) and 95% confidence intervals (CIs). RESULTS: We identified 54,804 cases of CRC (2,557 EOCRCs) and 261,089 controls. Compared with none, previous antibiotic use was not associated with EOCRC risk after adjustment for potential confounders (aOR 1.06, 95% CI: 0.96, 1.17) with similarly null findings when stratified by anatomic tumor site. In contrast, previous antibiotic use was weakly associated with elevated risk for CRC at any age (aOR 1.05, 95% CI: 1.02, 1.07). A potential but modest link between broad-spectrum antibiotic use and EOCRC was observed (aOR 1.13, 95% CI: 1.02, 1.26). DISCUSSION: We found no conclusive evidence that antibiotics are associated with EOCRC risk. Although antibiotic use was weakly associated with risk of CRC at any age, the magnitude of association was modest, and the study period was relatively short.


Assuntos
Neoplasias Colorretais , Adolescente , Adulto , Antibacterianos/efeitos adversos , Estudos de Casos e Controles , Estudos de Coortes , Neoplasias Colorretais/induzido quimicamente , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Humanos , Incidência , Pessoa de Meia-Idade
14.
Cancer Prev Res (Phila) ; 15(4): 265-272, 2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-34980677

RESUMO

Prospective data examining the association of aspirin use, according to dose and duration, with long-term risk of gastric adenocarcinoma in non-Asian cohorts are lacking. We evaluated the association between aspirin use and risk of gastric adenocarcinoma in two large prospective U.S. cohort studies, the Nurses' Health Study and the Health Professionals Follow-up Study. Cox proportional hazards regression models were used to calculate multivariable adjusted HRs and 95% confidence intervals (CI). Among the 159,116 participants, we documented 316 gastric adenocarcinoma cases (176 women, 140 men) over 34 years encompassing 4.5 million person-years. Among women, regular aspirin use (at least two times or more per week) was significantly associated with lower risk of gastric adenocarcinoma (multivariable HR, 0.52; 95% CI, 0.37-0.73) compared with nonregular use. However, regular aspirin use was not associated with gastric adenocarcinoma risk among men (multivariable HR, 1.08; 95% CI, 0.77-1.52; Pheterogeneity for sex = 0.003). Among women, the lower risk of gastric adenocarcinoma was more apparent with increasing duration of aspirin use (Ptrend < 0.001) and more than five tablets per week (multivariable HR, 0.51; 95% CI, 0.31-0.84). Regular, long-term aspirin use was associated with lower risk of gastric adenocarcinoma among women, but not men. The benefit appeared after at least 10 years of use and was maximized at higher doses among women. The heterogeneity by sex in the association of aspirin use with risk of gastric adenocarcinoma requires further investigation. PREVENTION RELEVANCE: Novel prevention is urgently needed to reduce incidence and mortality of gastric cancer. We found that regular aspirin use was associated with lower risk of gastric adenocarcinoma among women, but not men. The benefit appeared after at least 10 years of use and was maximized at higher doses among women. See related Spotlight, p. 213.


Assuntos
Adenocarcinoma , Neoplasias Gástricas , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/epidemiologia , Adenocarcinoma/prevenção & controle , Anti-Inflamatórios não Esteroides/uso terapêutico , Aspirina/uso terapêutico , Feminino , Seguimentos , Humanos , Masculino , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/prevenção & controle
15.
Int J Cancer ; 150(4): 654-662, 2022 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-34591977

RESUMO

Previous studies have shown that the addition of carboplatin to neoadjuvant chemotherapy improved the pathologic complete response (pCR) rate in patients suffering from triple-negative breast cancer (TNBC) and patients who obtained a pCR could achieve prolonged event-free survival (EFS) and overall survival (OS). However, no studies have assessed the effects of the combination of docetaxel and carboplatin without anthracycline with taxane-based and anthracycline-based regimens. The NeoCART study was designed as a multicenter, randomized controlled, open-label, phase II trial to assess the efficacy and safety of docetaxel combined with carboplatin in untreated stage II-III TNBC. All eligible patients were randomly assigned, at a 1:1 ratio, to an experimental docetaxel plus carboplatin (DCb) for six cycles group (DCb group) or an epirubicin plus cyclophosphamide for four cycles followed by docetaxel for four cycles group (EC-D group). PCR (ypT0/is ypN0) was evaluated as the primary outcome. Between 1 September 2016 and 31 December 2019, 93 patients were randomly assigned and 88 patients were evaluated for the primary endpoint (44 patients in each group). In the primary endpoint analysis, 27 patients in the DCb group (61.4%, 95% CI 47.0-75.8) and 17 patients in the EC-D group achieved a pCR (38.6%, 95% CI 24.3-53.0; odds ratio 2.52, 95% CI 2.4-43.1; Pnoninferiority = .004). Noninferiority was met, and the DCb regimen was confirmed to be superior to the EC-D regimen (P = .044, superiority margin of 5%). At the end of the 37-month median follow-up period, OS and EFS rates were equivalent in both groups.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Adulto , Carboplatina/administração & dosagem , Carboplatina/efeitos adversos , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Docetaxel/administração & dosagem , Docetaxel/efeitos adversos , Epirubicina/administração & dosagem , Epirubicina/efeitos adversos , Feminino , Humanos , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estudos Prospectivos , Neoplasias de Mama Triplo Negativas/mortalidade
16.
Cancer Immunol Immunother ; 71(4): 933-942, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34529108

RESUMO

BACKGROUND: Despite heightened interest in early-onset colorectal cancer (CRC) diagnosed before age 50, little is known on immune cell profiles of early-onset CRC. It also remains to be studied whether CRCs diagnosed at or shortly after age 50 are similar to early-onset CRC. We therefore hypothesized that immune cell infiltrates in CRC tissue might show differential heterogeneity patterns between three age groups (< 50 "early onset," 50-54 "intermediate onset," ≥ 55 "later onset"). METHODS: We examined 1,518 incident CRC cases with available tissue data, including 35 early-onset and 73 intermediate-onset cases. To identify immune cells in tumor intraepithelial and stromal areas, we developed three multiplexed immunofluorescence assays combined with digital image analyses and machine learning algorithms, with the following markers: (1) CD3, CD4, CD8, CD45RO (PTPRC), and FOXP3 for T cells; (2) CD68, CD86, IRF5, MAF, and MRC1 (CD206) for macrophages; and (3) ARG1, CD14, CD15, CD33, and HLA-DR for myeloid cells. RESULTS: Although no comparisons between age groups showed statistically significant differences at the stringent two-sided α level of 0.005, compared to later-onset CRC, early-onset CRC tended to show lower levels of tumor-infiltrating lymphocytes (P = 0.013), intratumoral periglandular reaction (P = 0.025), and peritumoral lymphocytic reaction (P = 0.044). Compared to later-onset CRC, intermediate-onset CRC tended to show lower densities of overall macrophages (P = 0.050), M1-like macrophages (P = 0.062), CD14+HLA-DR+ cells (P = 0.015), and CD3+CD4+FOXP3+ cells (P = 0.039). CONCLUSIONS: This hypothesis-generating study suggests possible differences in histopathologic lymphocytic reaction patterns, macrophages, and regulatory T cells in the tumor microenvironment by age at diagnosis.


Assuntos
Neoplasias Colorretais , Microambiente Tumoral , Neoplasias Colorretais/patologia , Antígenos HLA-DR , Humanos , Linfócitos do Interstício Tumoral , Macrófagos , Pessoa de Meia-Idade
17.
J Stroke Cerebrovasc Dis ; 31(2): 106222, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34839235

RESUMO

OBJECTIVE: A self-rating post stroke depression scale (PSDS) showed a good reliability and validity to assess severity of depressive symptoms among stroke patients. This study aimed to retest the psychometric properties of PSDS in different types of post-stroke depression (PSD). MATERIALS AND METHODS: A total of 170 stroke patients were recruited in the study. 82 and 25 patients were respectively diagnosed as PSD symptoms disorder (PSDSD) and PSD disorder (PSDD) patients according to their respective diagnostic criteria. The PSDS and the 9-item Patient Health Questionnaire (PHQ-9) were used to assess the severity of depression. Cronbach α, Spearman rank coefficient and independent sample t-test were conducted to examine reliability, internal consistency and discriminate validity. Then the receiver operating characteristic curve and Youden index were used to performance evaluation and cut-off value respectively in different subtypes of PSD patients. RESULTS: The Cronbach α of PSDS was 0.857, indicting a good reliability. The Spearman correlation coefficient between PSDS and PHQ-9 was 0.942 (P<0.001). The discriminate validity displayed significant difference between PSDSD as well as PSDD and no depression patients (all P<0.001). 5/24 and 10/24 were the cut-off value for PSDSD and PSDD patients. CONCLUSIONS: PSDS is a useful screen tool with an acceptable psychometric properties for estimation of different subtypes of PSD patients.


Assuntos
Depressão , Questionário de Saúde do Paciente , Acidente Vascular Cerebral , Depressão/diagnóstico , Depressão/etiologia , Humanos , Psicometria , Reprodutibilidade dos Testes , Acidente Vascular Cerebral/complicações
18.
Mol Biol Evol ; 39(2)2022 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-34893856

RESUMO

Domestic sheep and their wild relatives harbor substantial genetic variants that can form the backbone of molecular breeding, but their genome landscapes remain understudied. Here, we present a comprehensive genome resource for wild ovine species, landraces and improved breeds of domestic sheep, comprising high-coverage (∼16.10×) whole genomes of 810 samples from 7 wild species and 158 diverse domestic populations. We detected, in total, ∼121.2 million single nucleotide polymorphisms, ∼61 million of which are novel. Some display significant (P < 0.001) differences in frequency between wild and domestic species, or are private to continent-wide or individual sheep populations. Retained or introgressed wild gene variants in domestic populations have contributed to local adaptation, such as the variation in the HBB associated with plateau adaptation. We identified novel and previously reported targets of selection on morphological and agronomic traits such as stature, horn, tail configuration, and wool fineness. We explored the genetic basis of wool fineness and unveiled a novel mutation (chr25: T7,068,586C) in the 3'-UTR of IRF2BP2 as plausible causal variant for fleece fiber diameter. We reconstructed prehistorical migrations from the Near Eastern domestication center to South-and-Southeast Asia and found two main waves of migrations across the Eurasian Steppe and the Iranian Plateau in the Early and Late Bronze Ages. Our findings refine our understanding of genome variation as shaped by continental migrations, introgression, adaptation, and selection of sheep.


Assuntos
Genoma , Carneiro Doméstico , Animais , Ásia , Europa (Continente) , Variação Genética , Irã (Geográfico) , Polimorfismo de Nucleotídeo Único , Análise de Sequência de DNA , Ovinos/genética , Carneiro Doméstico/genética
19.
Cancer Epidemiol ; 76: 102079, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34894590

RESUMO

BACKGROUND: The United States Preventative Services Taskforce recently updated lung cancer screening guidelines for U.S. adults with high-risk smoking histories. This has generated a previously undescribed patient population in which the prevalence of cigarette and e-cigarette use has not been described. METHODS: We performed a cross-sectional study using population-based data from the Behavioral Risk Factor Surveillance System (2017-2018). We defined lung cancer screening eligibility as adults 50-80 years old with ≥ 20 pack-year smoking history who were currently smoking or quit within the last 15 years. We assessed several smoking-related outcomes including current cigarette use, ever e-cigarette use, and current e-cigarette use among respondents. RESULTS: Among 7541 screening-eligible adults, current cigarette use was reported by 3604 (47.8%) participants. Ever and current e-cigarette use were reported by 3003 (39.8%) and 670 (8.9%) participants, respectively. Compared to individuals who were previously eligible for screening, individuals newly eligible for screening (i.e., between 50 and 55 years old with a 20-30 pack-year smoking history) were more likely to currently smoke (aOR 1.828, 95% CI 1.649-2.026, p < 0.001). While newly eligible respondents were more likely to report a history of ever using an e-cigarette (aOR 1.144, 95% CI 1.034-1.266, p = 0.009), current e-cigarette use was similar in this group compared to those individuals who were previously screening-eligible (aOR 1.014, 95% CI 0.844-1.219, p = 0.88). CONCLUSIONS: Cigarette and e-cigarette exposure are common among U.S. adults who are eligible for lung cancer screening. Expanded USPSTF criteria will capture a patient population with greater exposure to both of these products.


Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Neoplasias Pulmonares , Produtos do Tabaco , Vaping , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Detecção Precoce de Câncer , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/etiologia , Pessoa de Meia-Idade , Prevalência , Estados Unidos/epidemiologia
20.
Cancer Epidemiol Biomarkers Prev ; 31(1): 210-220, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34737207

RESUMO

BACKGROUND: Fusobacterium nucleatum (F. nucleatum) activates oncogenic signaling pathways and induces inflammation to promote colorectal carcinogenesis. METHODS: We characterized F. nucleatum and its subspecies in colorectal tumors and examined associations with tumor characteristics and colorectal cancer-specific survival. We conducted deep sequencing of nusA, nusG, and bacterial 16s rRNA genes in tumors from 1,994 patients with colorectal cancer and assessed associations between F. nucleatum presence and clinical characteristics, colorectal cancer-specific mortality, and somatic mutations. RESULTS: F. nucleatum, which was present in 10.3% of tumors, was detected in a higher proportion of right-sided and advanced-stage tumors, particularly subspecies animalis. Presence of F. nucleatum was associated with higher colorectal cancer-specific mortality (HR, 1.97; P = 0.0004). This association was restricted to nonhypermutated, microsatellite-stable tumors (HR, 2.13; P = 0.0002) and those who received chemotherapy [HR, 1.92; confidence interval (CI), 1.07-3.45; P = 0.029). Only F. nucleatum subspecies animalis, the main subspecies detected (65.8%), was associated with colorectal cancer-specific mortality (HR, 2.16; P = 0.0016), subspecies vincentii and nucleatum were not (HR, 1.07; P = 0.86). Additional adjustment for tumor stage suggests that the effect of F. nucleatum on mortality is partly driven by a stage shift. Presence of F. nucleatum was associated with microsatellite instable tumors, tumors with POLE exonuclease domain mutations, and ERBB3 mutations, and suggestively associated with TP53 mutations. CONCLUSIONS: F. nucleatum, and particularly subspecies animalis, was associated with a higher colorectal cancer-specific mortality and specific somatic mutated genes. IMPACT: Our findings identify the F. nucleatum subspecies animalis as negatively impacting colorectal cancer mortality, which may occur through a stage shift and its effect on chemoresistance.


Assuntos
Neoplasias Colorretais , Fusobacterium nucleatum , Carcinogênese , Neoplasias Colorretais/genética , Humanos , RNA Ribossômico 16S
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