BRCA1-Associated Protein 1 (BAP1) germline mutations predispose individuals to cancers, including uveal melanoma (UM) and cutaneous melanoma (CM). BAP1 loss is common in UM and is associated with a ...worse prognosis. BAP1 loss is rare in CM and the outcome is unclear.
UM and CM data was retrieved from The Cancer Genome Atlas (TCGA) database. Cox regression model was performed to examine whether BAP1 mRNA levels or copy number variations were associated with overall survival (OS).
BAP1-low mRNA predicted a poor OS in UM (HR = 9.57, 95% CI: 2.82, 32.5) but a contrasting better OS in CM (HR = 0.73, 95% CI: 0.56, 0.95). These results remained unchanged after adjusting for sex, age, and stage in UM and CM, or after adjusting for ulceration or Breslow depth in CM. Additionally, low BAP1 mRNA predicted a better OS in CM patients older than 50 years but not in younger patients. Co-expression and enrichment analysis revealed differential genes and mutations that were correlated with BAP1 expression levels in UM and CM tumors.
Low BAP1 mRNA was significantly associated with a better OS in CM patients, in sharp contrast to UM. High BAP1 expression in CM was significantly associated with over-expressed CDK1, BCL2, and KIT at the protein level which may explain the poor OS in this sub-group of patients. Function of BAP1 was largely different in CM and UM despite of a small subset of shared co-expressed genes.
Dietary lignans, quercetin and resveratrol have oestrogenic properties, and animal studies suggest that they synergistically decrease cancer risk. A protective effect of lignans on the development of ...oesophageal cancer in humans has recently been demonstrated, and the present study aimed to test whether these three phytochemicals synergistically decrease the risk of oesophageal cancer. Data from a Swedish nationwide population-based case–control study that recruited 181 cases of oesophageal adenocarcinoma (OAC), 158 cases of oesophageal squamous-cell carcinoma (OSCC), 255 cases of gastro-oesophageal junctional adenocarcinoma (JAC) and 806 controls were analysed. Exposure data were collected through face-to-face interviews and questionnaires. The intake of lignans, quercetin and resveratrol was assessed using a sixty-three-item FFQ. Reduced-rank regression was used to assess a dietary pattern, and a simplified dietary pattern score was categorised into quintiles on the basis of the distribution among the control subjects. Unconditional multivariable logistic regression provided OR with 95 % CI, adjusted for all the potential risk factors. A dietary pattern rich in lignans, quercetin and resveratrol was mainly characterised by a high intake of tea, wine, lettuce, mixed vegetables, tomatoes, and whole-grain bread and a low intake of milk. There were dose-dependent associations between simplified dietary pattern scores and all types of oesophageal cancer (all P for trend < 0·05). On comparing the highest quintiles with the lowest, the adjusted OR were found to be 0·24 (95 % CI 0·12, 0·49) for OAC, 0·31 (95 % CI 0·15, 0·65) for OSCC, and 0·49 (95 % CI 0·28, 0·84) for JAC. The results of the present study indicate that a dietary pattern characterised by the intake of lignans, quercetin and resveratrol may play a protective role in the development of oesophageal cancer in the Swedish population.
The potential environmental impact and increased operational costs associated with the upgrading and renovation of sewage treatment plants are acknowledged. This study employs the upgrading and ...expansion project of a municipal sewage plant in Dongguan City, Guangdong Province, as a case study. Utilizing the principles and methods of the Life Cycle Assessment (LCA), a comprehensive assessment of the environmental benefits during the upgrading and renovation process of the sewage treatment plant, is conducted and targeted solutions are proposed. The research findings indicate that upgrading and renovating sewage treatment plants can significantly augment the adverse environmental effects of such facilities. Therefore, this study strategically proposes measures such as the utilization of clean energy, sludge resource utilization, and recycled water use as carbon emission reduction pathways. Through calculations, it is demonstrated that the utilization of clean energy and sludge resource can respectively reduce electricity consumption by 12.41% and 59.06%. Concurrently, recycled water use can lead to a reduction of 68.65% in carbon emissions, thereby markedly enhancing positive environmental outcomes.
Background: The role of the metabolic syndrome in the etiology of esophageal and gastric cancer is unclear. Methods: This was a large nationwide cohort study based on data from 11 prospective ...population-based cohorts in Norway with long-term follow-up, the Cohort of Norway (CONOR) and the third Nord-Trøndelag Health Study (HUNT3). The metabolic syndrome was assessed by objective anthropometric and metabolic biochemical measures and was defined by the presence of at least three of the following five factors: increased waist circumference, elevated triglycerides, low high-density lipoprotein cholesterol, hypertension and high glucose. Newly diagnosed cases of esophageal adenocarcinoma, esophageal squamous-cell carcinoma and gastric adenocarcinoma were identified from the Norwegian Cancer Registry. Hazard ratios (HRs) and 95 % confidence intervals (CIs) were estimated using Cox proportional hazard models with adjustment for potential confounders. Result: Among 192,903 participants followed up for an average of 10.6 years, 62 developed esophageal adenocarcinoma, 64 had esophageal squamous-cell carcinoma and 373 had gastric adenocarcinoma. The metabolic syndrome was significantly associated with an increased risk of gastric adenocarcinoma (HR 1.44, 95 % CI 1.14–1.82), but not associated with esophageal adenocarcinoma (HR 1.32, 95 % CI 0.77–2.26) or esophageal squamous-cell carcinoma (HR 1.08, 95 % CI 0.64–1.83). Increased waist circumference was associated with an increased HR of esophageal adenocarcinoma (HR 2.48, 95 % CI 1.27–4.85). No significant association was found between any single component of the metabolic syndrome and risk of esophageal squamous-cell carcinoma. High waist circumference (HR 1.71, 95 % CI 1.05–2.80), hypertension (HR 2.41, 95 % CI 1.44–4.03) and non-fasting glucose (HR 1.74, 95 % CI 1.18–2.56) were also related to an increased risk of gastric adenocarcinoma in women, but not in men. Conclusion: Metabolic syndrome was associated with an increased risk of gastric adenocarcinoma in women. Of the individual components of the metabolic syndrome, high waist circumference was positively associated with risk of esophageal adenocarcinoma. Positive associations were also observed for women between high waist circumference, hypertension, high non-fasting glucose and risk of gastric adenocarcinoma. However, further evidence is warranted due to the limited number of cases and the inability to effectively identify gastric cardia adenocarcinoma.
Macrovascular disease is tightly associated with obesity-induced metabolic syndrome. Sitagliptin (SIT), an orally stable selective inhibitor of Dipeptidyl peptidase-4 (DPP-4), has protective effects ...on endothelium. However, the mechanisms enabling SIT to exhibit resistance to diet-induced obesity (DIO) related with reactive oxygen species (ROS) and endoplasmic reticulum (ER) stress in the aorta and endothelial cells have not been reported yet. Therefore, the present study was conducted to determine if SIT exerts protective role in the thoracic aortas isolated from the high-fat diet (HFD)-treated rats and palmitate (PA)-treated endothelial cells by alleviating ROS and ER stress. Male Sprague Dawley rats were randomly divided into standard chow diet (SCD), HFD and HFD plus sitagliptin administration (HFD + SIT) groups. The rats of latter two groups were given HFD fodder for 12 weeks, then the HFD + SIT rats were treated with SIT (10 mg/kg/d) by intragastric administration for another 8 weeks. The body mass, vascular tension, serum oxidative stress indices and inflammatory parameters, pathological changes, protein expression of endothelial nitric oxide synthase (eNOS), the genes associated with ER stress and apoptosis in the thoracic aorta were measured. Furthermore, cell proliferation, ROS and the protein expression associated with ER stress (especially CHOP) and apoptosis were assessed in human umbilical vein endothelial cells (HUVECs) incubated with SIT and PA. Compared to the SCD rats, the HFD rats had higher serum lipid levels, decreased vascular tension, increased inflammation, oxidative and ER stress, and apoptosis of endothelial cells. PA promoted ROS generation, ER stress and apoptosis, inhibited cell proliferation in HUVECs. SIT treatment obviously ameliorated apoptosis via alleviating ROS and ER stress in the thoracic aortas isolated from HFD-fed rats and PA-treated HUVECs. The results suggest that SIT improved endothelial function via promoting cell proliferation and alleviating ROS-ER stress-CHOP pathway both
in vivo
and
in vitro
.
Background There are few population-based studies addressing the survival after resection for esophageal cancer. This study represents an update of a nationwide Swedish cohort initiated in 1987. ...Methods Based on data from the Swedish Patient Register, Swedish Cancer Register, and histopathologic records, 1,008 patients who had undergone esophageal resection as the only treatment for esophageal cancer were identified between January 1, 1987 and December 31, 2005. These were followed until death or emigration through linkage to the Swedish Total Population Register until January 1, 2009. Tumor stage, location, and histology were assessed from histopathologic reports, and comorbidities were assessed from the Patient Register. Cox proportional hazards regression models were used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) regarding survival. The results were adjusted for age, sex, comorbidity, tumor stage, location, histology, surgical radicality, and hospital volume. Results The proportion of patients surviving for 5 years increased from 19.7% in 1987-1991 to 30.7% in 1997-2000, but remained at 30.5% between 2001 and 2005. No difference in overall adjusted survival was found between the periods of 2001-2005 and 1997-2000 (adjusted HR, 0.89; 95% CI, 0.70–1.13). Thirty-day mortality decreased from 4.9% in 1997-2000 to 2.0% in 2001-2005, rendering an adjusted HR of 0.26 (95% CI, 0.08–0.87). Conclusion After adjusting for relevant prognostic factors, long-term population-based survival after resection for esophageal cancer was unchanged between 2001 and 2005 compared to 1997-2000, while the corresponding 30-day mortality improved.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Obesity increases the risk of several cancers, but it is uncertain whether weight reduction is followed by any decreased risk. To address this topic, we selected a group of patients representing a ...substantial weight loss starting at a defined time, ie, patients submitted to obesity surgery. We hypothesized that risk of obesity-related cancer decreases with time after obesity surgery.
A nationwide, population-based cohort study of obesity surgery in 1980-2006 as registered in the Swedish Patient Register. New cancers were identified through the Swedish Cancer Register. Cohort members' observed total number of overall obesity-related cancers and groups of obesity-related cancer (breast, prostate, colorectal, endometrial, kidney) were divided by the expected numbers, representing the baseline risk, thus calculating standardized incidence ratios (SIRs) with 95% confidence intervals (CIs). Time trends of SIR after obesity surgery were the main outcome measure.
Among a total of 13,123 obesity surgery patients, contributing with 125,049 person-years of follow-up, 296 new cases of obesity-related cancer were identified. There was no overall decrease in SIR of obesity-related cancer with increased time after obesity surgery (P for trend 0.40). Similarly, no statistically significant trends with follow-up time were found for cancer of the breast (P = 0.60), prostate (P = 0.34), endometrium (P = 0.83), or kidney (P = 0.42), while the risk of colorectal cancer increased with time (P for trend 0.01) after obesity surgery.
The weight reduction following obesity surgery might not be entailed by a decreased risk of obesity-related cancer with increasing follow-up time as compared with the baseline risk.
Cardiovascular disease (CVD) has become a major cause of morbidity and mortality in patients with type 2 diabetes mellitus (T2DM). Although there is also evidence that multifactorial interventions to ...control blood glucose, blood pressure, and lipid profiles can reduce macrovascular complications and mortality in patients with T2DM, the link between these risk factors has not been established.
On 10 December 2018, 1,920 people in four cities in Anhui Province were included. Latent category analysis (LCA) was used to explore the clustering mode of HRBs (health risk behaviors). The primary exposure was HRBs and exercise and diet interventions, and the primary outcome was CVD and other variables, including zMS, triglyceride-glucose index (TyG), TyG-WC (waist circumference), TyG-BMI, TG/HDL, and cardiovascular health (CVH). A multivariable logistic regression model was used to establish the relationship between HRBs, exercise, diet interventions, and CVD. Moderate analysis and mediation moderation analysis were employed by the PROCESS method to explore the relationship between these variables. Sensitivity analysis explored the robustness of the model.
The mean age was 57.10 ± 10.0 years old. Overall, CVD affects approximately 19.9% of all persons with T2DM. Macrovascular complications of T2DM include coronary heart disease, myocardial infarction (MI), cardiac insufficiency, and cerebrovascular disease. Elderly age (
= 22.70), no occupation (
= 20.97), medium and high socioeconomic status (SES) (
= 19.92), higher level of TyG-WC (
= 6.60), and higher zMS (
= 7.59) were correlated with high CVD. Many metabolic indices have shown a connection with T2DM combined with CVD, and there was a dose-response relationship between HRB co-occurrence and clustering of HRBs and zMS; there was a dose-response relationship between multifactorial intervention and CVH. In the mediation moderation analysis, there was an association between HRB, gender, TyG, TyG-BMI, and CVD. From an intervention management perspective, exercise and no diet intervention were more significant with CVD; moreover, there was an association between intervention management, gender, zMS, TyG-WC, TyG-BMI, TG/HDL, and CVD. Finally, there was an association between sex, CVH, and CVD. Sensitivity analysis demonstrated that our results were robust.
CVD is one of the common complications in patients with type 2 diabetes, and its long-term outcome will have more or less impact on patients. Our findings suggest the potential benefits of scaling up multifactorial and multifaceted interventions to prevent CVD in patients with T2DM.
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