Metastatic lung cancer is one of the most lethal forms of cancer and molecular pathways driving metastasis are still not clearly elucidated. Metastatic cancer cells undergo an epithelial-mesenchymal ...transition (EMT) where they lose their epithelial properties and acquire a migratory and invasive phenotype. Here we identify that the expression of microRNAs from the miR-200 family and the miR-183~96~182 cluster are significantly co-repressed in non-small cell lung cancer cell lines and primary tumors from multiple TCGA dataset with high EMT scores. Ectopic expression of the miR-183~96~182 cluster inhibited cancer cell migration and invasion, whereas its expression was tightly modulated by miR-200. We identified Foxf2 as a common, novel and direct target of both these microRNA families. Foxf2 expression tightly correlates with the transcription factor Zeb1 and is elevated in mesenchymal-like metastatic lung cancer cells. Foxf2 expression induced robust EMT, migration, invasion and metastasis in lung cancer cells, whereas Foxf2 inhibition significantly repressed these phenotypes. We also demonstrated that Foxf2 transcriptionally represses E-cadherin and miR-200, independent of Zeb1, to form a double-negative feedback loop. We, therefore, identified a novel mechanism whereby the miR-200 family and the miR-183~96~182 cluster inhibit lung cancer invasion and metastasis by targeting Foxf2.
The microRNA-371-373 (miR-371-373) cluster is specifically expressed in human embryonic stem cells (ESCs) and is thought to be involved in stem cell maintenance. Recently, microRNAs (miRNAs) of this ...cluster were shown to be frequently upregulated in several human tumors. However, the regulatory mechanism for the involvement of the miR-371-373 cluster in human ESCs or cancer cells remains unclear. In this study, we explored the relationship between this miRNA cluster and the Wnt/β-catenin-signaling pathway, which has been shown to be involved in both stem cell maintenance and tumorigenesis. We show that miR-371-373 expression is induced by lithium chloride and is positively correlated with Wnt/β-catenin-signaling activity in several human cancer cell lines. Mechanistically, three TCF/LEF1-binding elements (TBEs) were identified in the promoter region and shown to be required for Wnt-dependent activation of miR-371-373. Interestingly, we also found that miR-372&373, in turn, activate Wnt/β-catenin signaling. In addition, four protein genes related to the Wnt/β-catenin-signaling pathway were identified as direct targets of miR-372&373, including Dickkopf-1 (DKK1), a well-known inhibitor of Wnt/β-catenin signaling. Using a lentiviral system, we showed that overexpression of miR-372 or miR-373 promotes cell growth and the invasive activity of tumor cells as knockdown of DKK1. Taken together, our study demonstrates a novel β-catenin/LEF1-miR-372&373-DKK1 regulatory feedback loop, which may have a critical role in regulating the activity of Wnt/β-catenin signaling in human cancer cells.
It has been shown that asthma is significantly associated with the risk of cardiovascular disease (CVD). Under this background, this study aimed to systematically classify and summarize the ...epidemiological evidence of asthma and the risk of 4 specific cardiovascular diseases (CVDs) and cardiovascular mortality (CVM).
PubMed and Embase databases were searched from inception to December 1st, 2021 in order to identify relevant studies. The random-model was used to assess the pooled results. All pooled results were expressed as risk ratios (RRs) and corresponding 95% confidence intervals (CIs).
Finally, a total of 18 studies were included in the present meta-analysis. Compared with non-asthmatic group, patients with asthma had significantly increased risks of subsequent cardiovascular heart disease (CHD, RR 1.33; 1.19-1.50, I2=80.3%; p<0.001), and CVM (RR 1.35; 1.15-1.59, I2=0%; p<0.001). Similarly, the risks of heart failure (HF, RR 2.10; 1.98-2.22, I2=17.4%; p<0.001) and myocardial infraction (MI, RR 1.39; 1.16-1.66, I2=59.3%; p<0.001) were higher in the asthmatic population. However, the higher risk of atrial fibrillation (RR 1.70; 1.45-2.00, I2=0%; p<0.001) was observed only in the active asthmatic population.
In general, asthma is associated with subsequent increased risks of CHD, MI, AF, HF, and CVM. In addition, among patients with asthma, females have a higher risk of CHD than males, while active asthmatic patients have a higher risk of CVM than non-active asthmatic patients.
Introduction
The advent of laparoscopy has significantly reduced the morbidity associated with the majority of abdominal surgeries. In Senegal, the first studies evaluating this technique were ...published in the 1980s. The objective of this systematic review is to assess the evolution of laparoscopy research in Senegal.
Methods
A search of PubMed and Google Scholar was carried out without limit of publication date. The keywords used were “senegal” AND “laparoscop*”. Duplicates were removed, and remaining articles were assessed for selection criteria. We included all articles about laparoscopy published in Senegal. The parameters studied in each included article were the place and year of study, average age, sex ratio, assessed indications and results.
Results
41 Studies published between 1984 and 2021 met selection criteria. The average age of patients was 33 years (range 4.7–63). The sex ratio was 0.33. The main indications for laparoscopy according to the studies were: benign gastrointestinal disorders in 11 studies (26.8%), abdominal emergencies in 9 studies (22%), gallbladder surgery in 5 studies (12.2%), benign gynecological pathology in 6 studies (14.6%), malignant gynecological pathology in 2 studies (4.9%), diagnostic laparoscopy in 2 studies (4.9%), groin hernia repair in 2 studies (4.9%) and testicular pathology in 1 study (2.4%). Overall mortality was estimated at 0.9% (95% CI 0.6–1.3) and overall morbidity for all complications was estimated at 5% (95% CI 3.4–6.9).
Conclusions
This systematic review showed a predominance of the laparoscopy publications from the capital in Dakar with favorable outcomes. This technique should be popularized in the different regions of the country and its indications expanded.
Graphical abstract
A Monte Carlo method based on the GEANT4 toolkit has been developed to correct the full-energy peak (FEP) efficiencies of a high purity germanium (HPGe) detector equipped with a low background ...shielding system, and moreover evaluated using summing peaks in a numerical way. It is found that the FEP efficiencies of 60Co, 133Ba and 152Eu can be improved up to 18% by taking the calculated true summing coincidence factors (TSCFs) correction into account. Counts of summing coincidence γ peaks in the spectrum of 152Eu can be well reproduced using the corrected efficiency curve within an accuracy of 3%.
Summary
Background
Dermatomyositis (DM) is an autoimmune disease affecting primarily the skin, muscle and lung. Dysregulations of cytokines and chemokines are commonly found in inflammatory ...disorders.
Objectives
To investigate the association between serum cytokines and chemokines and clinical severity, especially cutaneous lesions and interstitial lung disease (ILD) in patients with DM and clinically amyopathic DM (CADM).
Methods
Clinical features, laboratory findings and serum of 40 patients with DM or CADM were collected and analysed. Serum cytokines and chemokines were measured by enzyme‐linked immunosorbent assay or cytometric bead array. A multiple unpaired t‐test was performed to compare cytokines and chemokines in patients with DM and healthy controls. Correlations of serum cytokines and chemokines with disease severity were evaluated by Spearman's rank correlation test.
Results
Serum interferon (IFN)‐β rs = 0·37, 95% confidence interval (CI) 0·078–0·62; P = 0·019 and CXCL10 (rs = 0·32, 95% CI to −0·004 to 0·57; P = 0·045) were significantly correlated with the Cutaneous Dermatomyositis Disease Area and Severity Index activity score in the subset of patients with DM or CADM. Serum levels of interleukin (IL)‐6, IL‐10, IL‐18 and IFN‐β were significantly higher in the patients with acute/subacute interstitial pneumonia (A/SIP) than in the subset without A/SIP (P < 0·05). IL‐6 (rs = 0·54, 95% CI 0·27–0·72; P < 0·001) and IL‐18 (rs = 0·46, 95% CI 0·21–0·65; P = 0·003) were significantly correlated with the serum level of anti‐melanoma differentiation‐associated protein 5 antibody.
Conclusions
Serum levels of IFN‐β and CXCL10 may be useful biomarkers for assessing cutaneous disease activity in patients with DM and CADM. In addition, serum IL‐6, IL‐10, IL‐18 and IFN‐β were highly correlated with the occurrence of A/SIP. These cytokines may play a role in the pathogenesis of DM and CADM.
What's already known about this topic?
The mechanism of cutaneous manifestations in dermatomyositis (DM) and clinically amyopathic DM (CADM) has not yet been elucidated.
Cellular immunity, cytokine pathways, mechanical stress and sun exposure are possible contributors.
The correlation between serum cytokines and chemokines and disease activity, including Cutaneous Dermatomyositis Disease Area and Severity Index and anti‐melanoma differentiation‐associated protein (MDA)5 antibody, remains to be explored further.
What does this study add?
Serum interleukin (IL)‐6, IL‐10, IL‐18 and interferon (IFN)‐β were highly correlated with the occurrence of acute/subacute interstitial pneumonia (A/SIP).
Serum levels of IL‐6 and IL‐18 were significantly correlated with anti‐MDA5 antibody, indicating that IL‐6 and IL‐18 may contribute to anti‐MDA5 antibody‐associated A/SIP.
We report the correlation between cytokines and serum levels of anti‐MDA5 antibody among Chinese patients with DM and CADM.
What is the translational message?
Serum levels of IFN‐β and CXCL10 may be useful biomarkers for assessing cutaneous disease activity in patients with DM and CADM.
Plain language summary available online
BRCA1 function is inactivated through BRCA1 promoter methylation in a substantial number of triple-negative breast cancers. We investigated the impact of BRCA1-methylation status on the efficacy of ...adjuvant chemotherapy in patients with triple-negative breast cancer or with non-triple-negative breast cancer.
BRCA1 promoter methylation was assessed in 1163 unselected breast cancer patients. Methylation was evaluated using a methylation-specific PCR (MSP) assay.
In the subgroup of 167 triple-negative breast cancer patients who received adjuvant chemotherapy, patients with BRCA1-methylated tumors had a superior 10-year disease-free survival (DFS)(78% versus 55%, P = 0.009) and 10-year disease-specific survival (DSS) (85% versus 69%, P = 0.024) than those with BRCA1-unmethylated tumors, and BRCA1 methylation was an independent favorable predictor of DFS and DSS in a multivariate analysis in this subgroup DFS: hazard ratio (HR) = 0.45; 95% confidence interval (CI) 0.24–0.84; P = 0.019; DSS: HR = 0.43; 95% CI = 0.19–0.95; P = 0.044. In contrast, in 675 non-triple-negative breast cancer patients who received adjuvant chemotherapy, BRCA1 methylation was an unfavorable predictor of DFS and DSS in univariate analysis (DFS: HR = 1.56; 95% CI 1.16–2.12; P = 0.003; DSS: HR = 1.53; 95% CI = 1.05–2.21; P = 0.026).
Triple-negative breast cancer patients with BRCA1-methylated tumors are sensitive to adjuvant chemotherapy and have a favorable survival compared with patients with BRCA1-unmethylated triple-negative tumors.
Purpose
To realize a systematic review to evaluate groin hernia surgery for adults in sub-Saharan Africa.
Methods
We conducted a systematic review and meta-analysis, the primary objective of which ...was to determine the surgical techniques used for unilateral groin hernia surgery in sub-Saharan Africa. Studies published in the last 20 years were considered. A meta-analysis estimated the pooled prevalence with 95% confidence interval (CI) of mortality, chronic pain and recurrence. A subgroup analysis compared the rate of complications between complicated or uncomplicated hernia.
Results
We included 113 articles. The most used technique was Bassini in 40.1%, followed by Lichtenstein in 29.9% and Shouldice in 12.6%. The overall mortality rate was 0.6% (95% CI 0.4–0.9). The pooled recurrence rate was 1.4% (95% CI 1.05–1.9). The pooled rate of chronic pain was 2.7% (95% CI 1.9–3.7). We found that mortality rate for complicated hernias (6.4%) was higher compared to uncomplicated hernias (0.2%). This difference was statistically significant
p
≤ 0.001; OR = 47.7; 95 CI (27.2–83.47).
Conclusion
This review showed that pure tissue repairs are the most used techniques with Bassini and Shouldice as leading procedures. The post-operative rates of recurrence and chronic pain are low. However, there is a high heterogeneity between studies than can underestimate these pooled prevalences. The consultation at complication stage remains frequent and associated with a higher mortality. Futures studies should focus on improving the quality of studies in terms of design and follow-up to increase the degree of evidence.
Abstract AIMS: To investigate the factors associated with recurrence and chronic pain after inguinal hernia surgery. SETTINGS AND DESIGN: A retrospective study was conducted over a period of 3 years ...and 5 months. MATERIALS AND METHODS: All patients over the age of 15 who underwent surgery for an inguinal hernia were included. STATISTICAL ANALYSIS USED: Factors associated with recurrence and chronic pain were evaluated using the Kaplan–Meier method and multivariate Cox proportional hazard model. RESULTS: During the study period, 195 patient records were collected. According to the European Hernia Society classification, 75.9% ( n = 148) of hernias were lateral, and 24.1% ( n = 47) were medial. The hernia was primary in 92.3% ( n = 180) of cases and recurrent in 7.7% ( n = 15). The hernia was strangulated in 29.7% ( n = 58) of cases. The surgical techniques used were: Bassini in 64.6% ( n = 126) of cases, Desarda in 23.6% ( n = 46), Lichtenstein in 9.7%, Mc Vay in two cases (1%) and trans-abdominal pre-peritoneal (TAPP) in two cases (1%). Acute postoperative complications were observed in 18 cases (9.2%). The average follow-up period was 25.4 months, with a range of 3–62.8 months. Chronic pain was observed in 18 cases (9.2%) and recurrence in 11 cases (5.6%). Multivariate analysis identified several prognostic factors, including recurrence (the existence of acute postoperative complications, P = 0.041); for chronic pain (a work with physical effort, P = 0.04; the existence of acute postoperative complications, P = 0.001, and mesh repair, P = 0.04). CONCLUSIONS: Our findings suggest that the management of acute complications, such as seroma, hematoma, and infection, is crucial to minimize the risk of long-term complications.
Human epidermal growth factor receptor 2 (HER2) Ile655Val polymorphism may affect the efficacy of trastuzumab treatment of breast cancer.
HER2 Ile655Val polymorphism was determined in 4167 patients ...with primary breast cancer using a polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) assay. We investigated the associations between the HER2 Ile655Val polymorphism and clinical outcomes in women with HER2-negative breast cancer and with HER2-positive breast cancer who received trastuzumab or who did not.
At a median follow-up of 44 months, HER2 Ile655Val polymorphism was not significantly associated with survival either in the entire study population of 4167 patients or in 2976 HER2-negative breast cancer patients. Among 816 HER2-positive patients who received adjuvant chemotherapy and/or endocrine therapy without trastuzumab treatment, patients with the Val/Ile or the Val/Val genotype had a significantly worse disease-free survival (DFS) and distant DFS (DDFS) than those with the Ile/Ile genotype (DFS, adjusted hazard ratio HR 1.5; 95% confidence interval CI 1.0–2.3; P = 0.037; DDFS, adjusted HR 1.9; 95% CI 1.2–2.9 P = 0.005). In contrast, among 212 HER2-positive patients who received chemotherapy in combination with trastuzumab treatment, patients with the Val/Ile or the Val/Val genotype had a significantly better DFS and DDFS than those with the Ile/Ile genotype (5-year DFS, 100% versus 83%; P = 0.008; 5-year DDFS, 100% versus 89%; P = 0.031).
HER2 Ile655Val polymorphism affects the function of HER2 gene only restricted in HER2-positive breast cancers. HER2-positive breast cancer patients with the Val variant have an aggressive phenotype, but are sensitive to trastuzumab treatment.
PDF
