Recent evidence suggests that neutrophil gelatinase-associated lipocalin (NGAL) expression is induced in many types of human cancer, while detection of its complex with matrix metalloproteinase-9 ...(MMP-9) is correlated with cancer disease status. We aim to evaluate the serum expression of MMP-9, NGAL and their complex (MMP-9/NGAL) during the diagnostic work-up of women with breast abnormalities and investigate their correlation with disease severity.
The study included 113 women with non-palpable breast lesions undergoing vacuum-assisted breast biopsy for histological diagnosis, and 30 healthy women, which served as controls. Expression levels of MMP-9, NGAL and their complex MMP-9/NGAL were determined in peripheral blood samples with immunoenzymatic assays.
Women with invasive ductal carcinoma exhibited significantly increased levels of MMP-9, NGAL and MMP-9/NGAL compared to healthy controls (MMP-9: p < 0.003, NGAL: p < 0.008 MMP-9/NGAL: p < 0.01). Significant correlations were observed between MMP-9 and NGAL serum levels and breast disease severity score (r = 0.229, p < 0.006 and r = 0.206, p < 0.01, respectively), whereas a non-significant correlation was found for their complex. MMP-9, NGAL and their complex MMP-9/NGAL levels were not correlated with either Body Mass Index (BMI) or age of patients.
These findings suggest that the serum measurement of MMP-9 and NGAL may be useful in non-invasively monitoring breast cancer progression, while supporting their potential role as early biomarkers of breast disease status.
The aim of this study was to investigate whether the presence of benign or malignant nodular thyroid disease affects levels of circulating angiogenesis cytokines.
In this study we investigated levels ...of angiopoietin – 1 and -2 (Ang-1 and Ang-2 respectively), vascular endothelial growth factor –A (VEGF-A), galectin-3 (Gal-3), urokinase plasminogen activator receptor (uPAR) and plasminogen activation inhibitor – 1 (PAI-1) in 40 patients with differentiated thyroid cancer (DTC), 45 with thyroid papillary microcarcinoma (mPTC), 53 patients with multinodular goiter (MNG) and 58 controls. Six months after surgery 28 patients resubmitted blood samples. The diagnostic value of Ang-1 levels was evaluated with receiver operating characteristic (ROC) curves. Results: Statistically significant lower levels of Ang-1 were observed in DTC and MNG patients compared to controls (p<.05). No significant differences were observed in the levels of the other factors. The area under ROC curves for Ang-1 discerning DTC, mPTC and MNG from control were 0.68, 0.66 and 0.71 respectively. A significant increase in Ang-1 levels (p<.05) was documented in the subset of patients that underwent thyroidectomy. Thyroidectomy did not influence levels of the other factors.
Our results suggest an association between low levels of Ang-1 and the presence of underlying benign or malignant nodular thyroid disease.
Background: Angiogenesis is a hallmark of breast cancer (BC) and is mediated by the vascular endothelial growth factor (VEGF) signaling axis. It is regulated by different proangiogenic factors, ...including platelet-derived growth factor-CC (PDGF-CC) and heparin-binding EGF-like growth factor (HB-EGF), as well as co-receptors, such as neuropilin-1, which could have prognostic implications in BC patients. Patients and methods: We assessed the serum levels of VEGF, HB-EGF, PDGF-CC and neuropilin-1 in 205 patients with early BC (invasive, n = 187; in situ, n = 18) and in 31 healthy donors (HD) and investigated the potential associations with clinical and histopathological parameters. Results: VEGF serum levels were significantly higher in patients with invasive versus ductal carcinomas in situ. PDGF-CC serum concentrations varied among BC molecular subtypes. Furthermore, we observed a differential expression of most biomarkers between overweight/obese (body mass index (BMI) ≥ 25 kg/m2) and non-obese patients among the BC molecular subtypes. Finally, the classification of subjects according to menopausal status revealed a significant difference in specific biomarker levels between patients and HD. Conclusion: The serum concentrations of angiogenic molecules differ among breast cancer molecular subtypes and are affected by the BMI and menopausal status, which could have possible clinical or prognostic implications.
Summary
Differentiated thyroid cancer (DTC) is the most common malignancy of the endocrine system. There has been a significant increase in its incidence over the past two decades attributable mainly ...to the use of more sensitive diagnostic modalities. Ultrasound‐guided fine needle aspiration cytology is the mainstay of diagnosis of benign disorders and malignancy. However, approximately 20% of lesions cannot be adequately categorized as benign or malignant. In the postoperative setting, monitoring of thyroglobulin (Tg) levels has been employed for the detection of disease recurrence. Unfortunately, Tg antibodies are common and interfere with Tg measurement in this subset of patients. Despite this limitation, Tg remains the sole widely used thyroid cancer biomarker in the clinical setting. In an attempt to bypass antibody interference, research has focused mainly on mRNA targets thought to be exclusively expressed in thyroid cells. Tg and thyroid stimulating hormone receptor (TSHR) mRNA have been extensively studied both for discerning between benign disease and malignancy and in postoperative disease surveillance. However, results among reports have been inconsistent probably reflecting considerable differences in methodology. Recently, microRNA (miRNA) targets are being investigated as potential biomarkers in DTC. MiRNAs are more stable molecules and theoretically are not as vulnerable as mRNA during manipulation. Initial results have been encouraging but large‐scale studies are warranted to verify and elucidate their potential application in diagnosis and postoperative surveillance of thyroid cancer. Several other novel targets, primarily mutations and circulating cells, are currently emerging as promising thyroid cancer circulating biomarkers. Although interesting and intriguing, data are limited and derive from small‐scale studies in specific patient cohorts. Further research findings demonstrating their value are awaited with anticipation.
Irisin is a recently discovered myokine, involved in the browning of white adipose tissue. To date, its function has been mainly associated with energy homeostasis and metabolism, and it has been ...proposed as a promising therapeutic target for obesity and metabolic diseases. This is the first study investigating the role of irisin in human breast cancer.
Participants included one hundred and one (101) female patients with invasive ductal breast cancer and fifty one (51) healthy women. Serum levels of irisin, leptin, adiponectin and resistin were quantified in duplicates by ELISA. Serum levels of CEA, CA 15-3 and Her-2/neu were measured on an immunology analyzer. The association between irisin and breast cancer was examined by logistic regression analysis. The feasibility of serum irisin in discriminating breast cancer patients was assessed by ROC curve analysis. Potential correlations with demographic, anthropometric and clinical parameters, with markers of adiposity and with breast tumor characteristics were also investigated.
Serum levels of irisin were significantly lower in breast cancer patients compared to controls (2.47 ± 0.57 and 3.24 ± 0.66 μg/ml, respectively, p < 0.001). A significant independent association between irisin and breast cancer was observed by univariate and multivariate analysis (p < 0.001). It was estimated that a 1 unit increase in irisin levels leads to a reduction in the probability of breast cancer by almost 90%. Irisin could effectively discriminate breast cancer patients at a cut-off point of 3.21 μg/ml, with 62.7% sensitivity and 91.1% specificity. A positive association with tumor stage and marginal associations with tumor size and lymph node metastasis were observed (p < 0.05, p < 0.01, p < 0.01, respectively).
Our novel findings implicate irisin in breast cancer and suggest its potential application as a new diagnostic indicator of the presence of disease.
Phosphatase and tensin homolog deleted on chromosome ten (PTEN) is one of the most frequently mutated human tumor suppressor genes, implicated in cell growth and survival and suppressing tumor ...formation. Loss of PTEN activity, either at the protein or genomic level, has been related to many primary and metastatic malignancies including breast cancer. The present study investigates the heterozygosity, mutation spectrum and protein expression of PTEN in 43 patients with breast cancer or precursor lesions of the breast and 10 healthy individuals. Microsatellite analysis at the PTEN locus using D10S215, D10S541 and D10S579 markers indicated that the observed heterozygosity (Ho) is lower than the expected heterozygosity (Hs) in benign and malignant breast disease. Mutational analysis in exons 1, 5, 7 and 9 of the PTEN gene revealed several mutations, most of which cause truncation of the PTEN protein and consequently loss of activity. Increased circulating levels of PTEN and phosphorylated PTEN protein were also observed by immunostaining in patients with breast cancer and precursor breast lesions. In support, increased PTEN protein expression was detected in corresponding tissue specimens. Our data suggest an association between breast cancer and PTEN mutations, resulting in the production of truncated forms of the corresponding protein, thus indicating that breast carcinogenesis is potentially related to PTEN loss of activity rather than loss of expression. Peripheral blood sampling may provide an advantageous application for the determination of PTEN gene mutations and its protein expression in human cancer.
Breast cancer is the most common type of cancer in females and is the leading cause of cancer-associated death among women, worldwide. The present study aimed to measure the serum levels of fatty ...acid-binding protein 4 (FABP4), retinol binding protein 4 (RBP4) and the MMP-9/neutrophil gelatinase-associated lipocalin (NGAL) complex in women diagnosed with breast cancer. Serum levels of the examined proteins were determined in the peripheral blood of patients via ELISA. Furthermore, whether the concentration of each protein was associated with breast cancer growth, molecular subtype, BMI, postmenopausal status, diabetes and the social background of patients was assessed. Women with invasive breast cancer demonstrated significantly higher levels of FABP4 (P=0.008). Additionally, considerably elevated FABP4 levels were demonstrated specifically in Luminal breast cancer cases (P<0.01). No significant association was recorded between RBP4 and breast cancer development. In addition, significantly lower levels of the MMP-9/NGAL complex were recorded in triple negative/HER-2 cases (P<0.05). BMI values appeared to influence the aforementioned associations, while significantly high serum levels of FABP4 and the MMP-9/NGAL complex were found in postmenopausal patients with breast cancer and a BMI ≥25 kg/m
(P<0.05). In addition, high levels of FABP4 were significantly associated with breast cancer patients with diabetes (P=0.05). However, no association was identified between RBP4, the MMP-9/NGAL complex and diabetes. In conclusion, FABP4 can be regarded as a biomarker of breast cancer growth, while both FABP4 and the MMP-9/NGAL complex may provide considerable information regarding the development of specific breast cancer subtypes. FABP4 and the MMP-9/NGAL complex may also be able to predict the development of breast cancer in postmenopausal patients with obesity.
Background
respiratory infections are transmitted by aerosol and droplets in close contact.AimWe investigated global
incidence after implementation of non-pharmaceutical interventions (NPIs) against ...COVID-19 in March 2020.MethodsWe surveyed
detections from laboratories and surveillance systems (national or regional) across the world from 1 April 2020 to 31 March 2021 and compared them with cases from corresponding months between 2017 and 2020. Macrolide-resistant
(MRMp) data were collected from 1 April 2017 to 31 March 2021.ResultsThirty-seven sites from 21 countries in Europe, Asia, America and Oceania submitted valid datasets (631,104 tests). Among the 30,617
detections, 62.39% were based on direct test methods (predominantly PCR), 34.24% on a combination of PCR and serology (no distinction between methods) and 3.37% on serology alone (only IgM considered). In all countries,
incidence by direct test methods declined significantly after implementation of NPIs with a mean of 1.69% (SD ± 3.30) compared with 8.61% (SD ± 10.62) in previous years (p < 0.01). Detection rates decreased with direct but not with indirect test methods (serology) (-93.51% vs + 18.08%; p < 0.01). Direct detections remained low worldwide throughout April 2020 to March 2021 despite widely differing lockdown or school closure periods. Seven sites (Europe, Asia and America) reported MRMp detections in one of 22 investigated cases in April 2020 to March 2021 and 176 of 762 (23.10%) in previous years (p = 0.04).ConclusionsThis comprehensive collection of
detections worldwide shows correlation between COVID-19 NPIs and significantly reduced detection numbers.
Breast and prostate constitute organs of intense steroidogenic activity. Clinical and epidemiologic data provide strong evidence on the influence of androgens and estrogens on the risk of typical ...hormone-dependent malignancies, like breast and prostate cancer. Recent studies have focused on the role of androgen metabolites in regulating androgen concentrations in hormone-sensitive tissues. Steroid glucuronidation has been suggested to have a prominent role in controlling the levels and the biological activity of unconjugated androgens. It is well-established that serum levels of androgen glucuronides reflect androgen metabolism in androgen-sensitive tissues. Quantitative analysis of androgen metabolites in blood specimens is the only minimally invasive approach permitting an accurate estimate of the total pool of androgens. During the past years, androgen glucuronides analysis most often involved radioimmunoassays (RIA) or direct immunoassays, both methods bearing serious limitations. However, recent impressive technical advances in mass spectrometry, and particularly in high performance liquid chromatography coupled with mass spectrometry (LC–MS/MS), have overcome these drawbacks enabling the simultaneous, quantitative analysis of multiple steroids even at low concentrations. Blood androgen profiling by LC–MS/MS, a robust and reliable technique of high selectivity, sensitivity, specificity, precision and accuracy emerges as a promising new approach in the study of human pathology. The present review offers a contemporary insight in androgen glucuronides profiling through the application of LC–MS/MS, highlighting new perspectives in the study of steroids and their implication in hormone-dependent malignancies.
Background
Thyroid disorders, including thyroid cancer and autoimmune thyroid diseases, have been closely associated with inflammation.
Objective
This study aims to investigate the role of ...inflammation in thyroid disease by assessing serum cytokine levels in patients with malignant and benign thyroid conditions.
Methods
Serum levels of ten interleukins (IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12 and IL-13) were quantitatively determined in 20 patients with thyroid cancer, 38 patients with benign thyroid disease and 50 healthy controls by multiplex technology.
Results
Serum IL-1β, IL-2, IL-4, IL-5 and IL-6 levels were strongly associated with each other. IL-10 and IL-12 correlated with IL-1β, IL-5, IL-6, and with each other. Age was inversely correlated with serum levels of IL-2, IL-4 and IL-13. A positive correlation between T3 and IL-13 levels was also observed. Significantly higher levels of IL-6, IL-7, IL-10 and IL-13, as well as significantly lower levels of IL-8 were observed in patients with benign and malignant thyroid disease compared to controls. The combination of IL-13 and IL-8 in a two-marker panel was highly efficient in discriminating thyroid disorders (AUC 0.90).
Conclusions
Malignant and benign thyroid conditions are associated with altered expression levels of interleukins, supporting the association between thyroid disease and underlying inflammatory processes.
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